Sample records for t2n0 glottic cancer

  1. Exclusive radiotherapy for stage T1-T2N0M0 lanryngeal cancer: retrospective study of 59 patients at CFB and CHU de Caen.

    PubMed

    Cuny, F; Géry, B; Florescu, C; Clarisse, B; Blanchard, D; Rame, J-P; Babin, E; De Raucourt, D

    2013-11-01

    Study of patients with stage T1N0M0 or T2N0M0 glottic cancer treated by exclusive radiotherapy and comparison of the survival and functional results of this series with those of the literature. Retrospective study of stage T1N0M0 or T2N0M0 glottic cancers diagnosed between 1st January 2000 and 31st December 2010 and treated by exclusive radiotherapy. Evaluation of survival, recurrence and larynx preservation rates. CLCC François-Baclesse and CHU de Caen. Fifty-nine patients (53 men and sixwomen) treated for glottic cancer (57 squamous cell carcinomas, two verrucous carcinomas) comprising 51 T1N0M0 and eight T2N0M0 tumours. Treatment with exclusive radiotherapy (mean dose of 70 Grays limited to the thyroid cartilage for 57 patients, with lymph node irradiation for two patients). In this series, five (9.8%) patients with stage T1N0M0 glottic cancer and three patients (37.5%) with stage T2N0M0 glottic cancer relapsed, corresponding to a global recurrence rate of 13.6%. Three of the eight recurrences involved lymph nodes exclusively (N), two patients relapsed exclusively at the primary tumour site (T) and three patients presented local and lymph node recurrence (T and N). Treatment consisted of salvage total laryngectomy with bilateral cervical lymph node dissection in three cases, bilateral cervical lymph node dissection and sensitized radiotherapy in two cases, exclusive chemotherapy in one case, cervical lymph node dissection and cervical radiotherapy in one case. The last patient with recurrence died prior to salvage therapy. The larynx preservation rate was 94.9%. In comparison with the literature, treatment of stage T1-T2N0M0 glottic cancer by exclusive radiotherapy gives very good results, with a larynx preservation rate of 95%. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  2. SU-E-T-63: Carotid Sparing Tomohelical Three Dimensional Conformal Radiotherapy for T1N0 Glottic Cancer

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hong, C; Ju, S; Ahn, Y

    2014-06-01

    Purpose: We investigated the dosimetric benefit and treatment efficiency of carotid-sparing TomoHelical (TH) three-dimensional conformal radiotherapy (3DCRT) for early glottic cancer. Methods: Computed tomography (CT) simulation was performed for 10 patients with early-stage (T1N0M0) glottic squamous cell carcinoma. The clinical target volume, planning target volume (PTV), carotid artery (CA), and spinal cord (SP) were delineated for each CT data set. Two-field 3DCRT (2F-3DCRT), three-field intensity-modulated radiation therapy (IMRT) (3F-IMRT), TomoHelical-IMRT (TH-IMRT), and TH-3DCRT plans were generated, with a total prescribed dose of 67.5 Gy in 30 fractions to the PTV for each patient. In order to evaluate plan quality, dosimetricmore » characteristics were compared in terms of the conformity index (CI) and homogeneity index (HI) for the PTV, V35, V50, and V63 for the CAs and in terms of the maximum dose for the SP. Additionally, treatment planning and delivery times were compared to evaluate treatment efficiency. Results: The CIs for 3F-IMRT (0.650±0.05), TH-IMRT (0.643±0.03), and TH-3DCRT (0.631±0.03) were much better than that for 2F-3DCRT (0.318±0.03). The HIs for TH-IMRT (1.053±0.01) and TH-3DCRT (1.055±0.01) were slightly better than those for 2F-3DCRT (1.062±0.01) and 3F-IMRT (1.091±0.007). 2F-3DCRT showed poor CA sparing in terms of the V35, V50, and V63 compared to 3F-IMRT, TH-IMRT, and TH-3DCRT (p<0.05), whereas there was no significant dose difference between 3F-IMRT, TH-IMRT, and TH-3DCRT (p>0.05). The maximum dose to the SP with all plans was below 45 Gy. The treatment planning times for 2F-3DCRT (5.9±0.66 min) and TH-3DCRT (7.32±0.94 min) were much lower than those for 3F-IMRT (45.51±2.76 min) and TH-IMRT (35.58±4.41 min), whereas the delivery times with all plans was below 3 minutes. Conclusion: TH-3DCRT showed excellent carotid sparing capability, comparable to that with TH-IMRT, with high treatment efficiency and short planning

  3. Simple Carotid-Sparing Intensity-Modulated Radiotherapy Technique and Preliminary Experience for T1-2 Glottic Cancer

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rosenthal, David I., E-mail: dirosenthal@mdanderson.or; Fuller, Clifton D.; Barker, Jerry L.

    2010-06-01

    Purpose: To investigate the dosimetry and feasibility of carotid-sparing intensity-modulated radiotherapy (IMRT) for early glottic cancer and to report preliminary clinical experience. Methods and Materials: Digital Imaging and Communications in Medicine radiotherapy (DICOM-RT) datasets from 6 T1-2 conventionally treated glottic cancer patients were used to create both conventional IMRT plans. We developed a simplified IMRT planning algorithm with three fields and limited segments. Conventional and IMRT plans were compared using generalized equivalent uniform dose and dose-volume parameters for in-field carotid arteries, target volumes, and organs at risk. We have treated 11 patients with this simplified IMRT technique. Results: Intensity-modulated radiotherapymore » consistently reduced radiation dose to the carotid arteries (p < 0.05) while maintaining the clinical target volume coverage. With conventional planning, median carotid V35, V50, and V63 were 100%, 100%, and 69.0%, respectively. With IMRT planning these decreased to 2%, 0%, and 0%, respectively (p < 0.01). Radiation planning and treatment times were similar for conventional radiotherapy and IMRT. Treatment results have been excellent thus far. Conclusions: Intensity-modulated radiotherapy significantly reduced unnecessary radiation dose to the carotid arteries compared with conventional lateral fields while maintaining clinical target volume coverage. Further experience and longer follow-up will be required to demonstrate outcomes for cancer control and carotid artery effects.« less

  4. Radiotherapy for T1-2N0 glottic cancer: a multivariate analysis of predictive factors for the long-term outcome in 1050 patients and a prospective assessment of quality of life and voice handicap index in a subset of 233 patients.

    PubMed

    Al-Mamgani, A; van Rooij, P H; Woutersen, D P; Mehilal, R; Tans, L; Monserez, D; Baatenburg de Jong, R J

    2013-08-01

    To evaluate the outcomes of patients with early stage glottic cancer (GC) treated with radiotherapy (RT). The current study report on a retrospective analysis of oncologic outcome of 1050 patients with T1-2N0 glottic cancer treated with radiotherapy. Prospective assessment of quality of life (QoL) and voice handicap index (VHI) was performed in all patients treated from 2006 onwards (n = 233). Local control (LC), regional control (RC), disease-free survival (DFS), overall survival (OS), quality of life and voice handicap index. After a median follow-up of 90 months (range 3-309), the actuarial rates of local control, regional control, disease-free survival and overall survival were 85%, 99%, 84% and 81% at 5 years and 82%, 98%, 80% and 61% at 10 years, respectively. On multivariate analysis, T2 tumours, smoking after radiotherapy and conventional radiation scheme correlated significantly with poor local control. Patients who continued smoking after radiotherapy had also significantly lower overall survival rates (OR 4.3, P < 0.001). Hypothyroidism was reported in 18% of patients. Slight and temporary deterioration of quality of life scores was reported. Patient-reported xerostomia and dysphagia at 48 months were -7.1 and -6.5, compared with baseline, respectively. Voice handicap index improved significantly from 37 at baseline to 18 at 48 months. Patients with T2b and those who continued smoking had significantly worse voice handicap index. In the current study, excellent outcome with good quality of life and voice handicap index scores were reported. T2 tumours, in particular T2b, and continuing smoking after radiotherapy correlated significantly with poor local control and worse voice handicap index. © 2013 John Wiley & Sons Ltd.

  5. Volumetric modulated arc radiotherapy sparing the thyroid gland for early-stage glottic cancer: A dosimetrical analysis.

    PubMed

    Kim, Eun Seok; Yeo, Seung-Gu

    2014-06-01

    Previous studies on advanced radiotherapy (RT) techniques for early stage glottic cancer have focused on sparing the carotid artery. However, the aim of the present study was to evaluate the dosimetric advantages of volumetric modulated arc therapy (VMAT) in terms of sparing the thyroid gland in early-stage glottic cancer patients. In total, 15 cT1N0M0 glottic cancer patients treated with definitive RT using VMAT were selected, and for dosimetric comparison, a conventional RT plan comprising opposed-lateral wedged fields was generated for each patient. The carotid artery, thyroid gland and spinal cord were considered organs at risk. The prescription dose was 63 Gy at 2.25 Gy per fraction. For the thyroid gland and carotid artery, all compared parameters were significantly lower with VMAT compared with conventional RT. For the thyroid gland, the median reduction rates of the mean dose (D mean ), the volume receiving ≥30% of the prescription dose (V 30 ) and the V 50 were 32.6, 40.9 and 46.0%, respectively. The D mean was 14.7±2.6 Gy when using VMAT compared with 22.2±3.9 Gy when using conventional RT. The differences between the techniques in terms of planning target volume coverage and dose homogeneity were not significant. When considering a recent normal tissue complication probability model, which indicated the mean thyroid gland dose as the most significant predictor of radiation-induced hypothyroidism, the dosimetric advantage shown in this study may be valuable in reducing hypothyroidism following RT for early stage glottic cancer patients.

  6. Utility approach to decision-making in extended T1 and limited T2 glottic carcinoma.

    PubMed

    van Loon, Yda; Stiggelbout, Anne M; Hakkesteegt, Marieke M; Langeveld, Ton P M; de Jong, Rob J Baatenburg; Sjögren, Elisabeth V

    2017-04-01

    It is still undecided if endoscopic laser surgery or radiotherapy is the preferable treatment in extended T1 and limited T2 glottic tumors. Health utilities assessed from patients can aid in decision-making. Patients treated for extended T1 or limited T2 glottic carcinoma by laser surgery (n = 12) or radiotherapy (n = 14) assigned health utilities using a visual analog scale (VAS), time tradeoff (TTO) technique and scored their voice handicap using the Voice Handicap Index (VHI). VAS and TTO scores were slightly lower for the laser group compared to the radiotherapy group, however, not significantly so. The VHI showed a correlation with the VAS score, which was very low in both groups and can be considered (near) normal. Patients show no clear preference for the outcomes of laser surgery or radiotherapy from a quality of life (QOL) or voice handicap point of view. These data can now be incorporated into decision-making models. © 2017 Wiley Periodicals, Inc. Head Neck, 2017 © 2016 Wiley Periodicals, Inc. Head Neck 39: 779-785, 2017. © 2017 Wiley Periodicals, Inc.

  7. Outcomes of radiofrequency ablation (RFA) and CO2 laser for early glottic cancer.

    PubMed

    Shuang, Yu; Li, Chao; Zhou, Xuan; Huang, Yongwang; Zhang, Lun

    2016-01-01

    In the present study, the voice and functional outcomes of radiofrequency ablation (RFA) and CO2 laser for early glottic cancer were evaluated. One hundred sixty eight patients with early glottic cancer from October 2007 to June 2015 were included. Ninety-seven patients underwent RFA and seventy-one patients underwent CO2 laser. The operation time and score of visual analog scale (VAS) for pain on the second day after surgery were recorded. The electronic laryngoscopy was performed at one week, one month and three months of postoperation. The operation time in RFA was shorter than that in CO2 laser (8.52±1.43min vs. 11.76±1.67min, P<0.05). There was no statistical difference in VAS scores between two operation methods (2.86±0.52 vs. 2.89±0.68, P>0.05). One month after operation, the mucosal recovery in RFA group was better than that in CO2 laser group (P<0.05). The alterations of acoustic parameters Jitter, Shimmer and HNR at three time points after operation showed statistical significances in both RFA and CO2 laser groups (P<0.05). The significant differences in acoustic parameters between two groups were also observed (P<0.05). There were no differences in three-year survival rate, local recurrence rate, recurrence rate with anterior commissure involvement and postoperative adhesion rate with anterior commissure between the patients with RFA and CO2 laser (P>0.05). No patient underwent tracheotomy and had symptoms of bucking, dyspnea, severe pain, hemoptysis and other serious complications. Both RFA and CO2 laser are safe and effective for the treatment of early glottic cancer. RFA has the advantage of quick voice recovery, low mucosa injury and short operation time, which is worthy for wide clinical application. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Early glottic cancer involving the anterior commissure treated by transoral laser cordectomy.

    PubMed

    Hoffmann, Caroline; Cornu, Nicolas; Hans, Stéphane; Sadoughi, Babak; Badoual, Cécile; Brasnu, Daniel

    2016-08-01

    Anterior commissure involvement is considered to be a risk factor for poorer outcomes after transoral laser cordectomy (TLC) for early glottic cancer. The objective of this study was to determine the outcomes and relevance of the tumor-node-metastasis (TNM) classification in a large series of patients with early glottic cancer involving the anterior commissure treated by TLC. The clinical and surgical parameters, as well as follow-up results, of the patients treated consecutively for early-stage glottic squamous cell carcinoma involving the anterior commissure (Tis, T1a, T1b, and T2) by transoral CO2 laser cordectomy in an urban academic medical center from January 2001 to March 2013 were analyzed retrospectively. The main outcomes measures were: 5-year disease free survival (DFS), ultimate local control with laser alone, laryngeal preservation, overall-survival (OS) rates, and disease-specific survival (DSS) rates (Kaplan-Meier). Ninety-six patients treated from January 2001 to March 2013 were included. The 5-year DFS and ultimate local control with laser alone rates were 61.7% and 74.4%, respectively. The laryngeal preservation rate was 93.4%; and the OS and DSS rates were 79.2% and 91.5%, respectively. Postoperative T classification (pT) status was not found to be a significant predictor of recurrences, but was predictive of more severe recurrences requiring other treatments than laser. TLC is an effective treatment for early stage glottic cancer involving the anterior commissure. The TNM classification is a relevant prognosis factor for severe recurrences. 4. Laryngoscope, 126:1817-1822, 2016. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

  9. Long-term follow-up and salvage surgery in patients with T2N0M0 squamous cell carcinoma of the glottic larynx who received concurrent chemoradiation therapy with carboplatin (CBDCA) - AUC 1.5 vs AUC 2.0.

    PubMed

    Furusaka, Tohru; Matsuda, Hiroshi; Saito, Tsutomu; Katsura, Yoshihisa; Ikeda, Minoru

    2012-11-01

    Patients who received concurrent chemoradiation therapy with carboplatin were followed up on a long-term basis. In 25 patients treated with carboplatin at an AUC of 2.0 mg/ml, the complete response (CR), 10-year survival, and 10-year larynx preservation rates were 96.0%, 91.1%, and 75.2%, respectively, and the safety margin for partial laryngectomy was 4 mm from the gross tumor. To perform long-term follow-up of the therapeutic outcomes of concurrent chemoradiation therapy and salvage surgery to determine the additive and synergistic effects of anticancer drugs combined with chemoradiotherapy. Fifty male patients (aged 33-76 years) with untreated T2N0M0 squamous cell carcinoma of the glottic larynx were included. Carboplatin was intravenously administered once a week for 4 weeks. Radiotherapy was delivered by an external beam of 4 MV linac X-ray (total = 66 Gy). The AUC 1.5 combination group showed overall response, CR, 5-year survival, 10-year survival, 5-year larynx preservation, and 10-year larynx preservation rates of 100.0%, 68.0%, 83.4%, 77.0%, 75.2%, and 75.2%, respectively. The AUC 2.0 combination group showed corresponding rates of 100%, 96.0%, 95.7%, 91.1%, 82.9%, and 72.7%, respectively. The most common side effects of grade 3 or more were leukopenia, neutropenia, and mucositis (stomatitis), and all were reversible. Thirteen patients (52.0%) in the AUC 1.5 combination group and nine patients (36.0%) in the AUC 2.0 combination group required salvage surgery. Histologically, concurrent chemoradiation therapy with carboplatin caused more severe cancer tissue degeneration. Pathological examinations indicated that the safety margin for partial laryngectomy was 4 mm from the gross tumor.

  10. Residual pathological stage at radical cystectomy significantly impacts outcomes for initial T2N0 bladder cancer.

    PubMed

    Isbarn, Hendrik; Karakiewicz, Pierre I; Shariat, Shahrokh F; Capitanio, Umberto; Palapattu, Ganesh S; Sagalowsky, Arthur I; Lotan, Yair; Schoenberg, Mark P; Amiel, Gilad E; Lerner, Seth P; Sonpavde, Guru

    2009-08-01

    We hypothesized that in patients with T2N0 stage disease at transurethral bladder tumor resection a lower residual cancer stage (P1N0 or less) at radical cystectomy may correlate with improved outcomes relative to those with residual P2N0 disease. We analyzed 208 patients with T2N0 stage disease at transurethral bladder tumor resection whose tumors were organ confined at radical cystectomy (P2 or lower, pN0). None received perioperative chemotherapy. Kaplan-Meier as well as univariable and multivariable Cox regression models addressed the effect of residual pT stage at radical cystectomy on recurrence and cancer specific mortality rates. Covariates consisted of age, gender, grade, lymphovascular invasion, carcinoma in situ, number of lymph nodes removed and year of surgery. Residual pT stage at radical cystectomy was P0 in 24 (11.5%) patients, Pa in 9 (4.3%), PCIS in 22 (10.6%), P1 in 35 (16.8%) and P2 in 118 (56.7%). Median followup of censored patients was 55.7 months for recurrence and 52.1 months for cancer specific mortality analyses. The 5-year recurrence-free survival rates of patients with P0/Pa/PCIS, P1 and P2 stage disease were 100%, 85% and 75%, respectively. The 5-year cancer specific survival rates for the same cohorts were 100%, 93% and 81%, respectively. On multivariable analysis the effect of residual stage P1 or lower at radical cystectomy achieved independent predictor status for recurrence (adjusted HR 0.20, p = 0.002) and cancer specific mortality (adjusted HR 0.24, p = 0.02). Down staging from initial T2N0 bladder cancer at transurethral bladder tumor resection to lower stage at radical cystectomy significantly reduces recurrence and cancer specific mortality. Further validation of this finding is warranted.

  11. Evidence-based practice: management of glottic cancer.

    PubMed

    Hartl, Dana M

    2012-10-01

    The main issue in the management of glottic squamous cell carcinoma, as for all cancers, is adequate disease control while optimizing functional outcomes and minimizing morbidity. This is true for early-stage disease as for advanced tumors. This article evaluates the current evidence for the diagnostic and pretherapeutic workup for glottic squamous cell carcinoma and the evidence concerning different treatment options for glottic carcinoma, from early-stage to advanced-stage disease. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. Risk of Fatal Cerebrovascular Accidents after External Beam Radiation Therapy for Early Stage Glottic Larynx Cancer

    PubMed Central

    Swisher-McClure, Samuel; Mitra, Nandita; Lin, Alexander; Ahn, Peter; Wan, Fei; O’Malley, Bert; Weinstein, Gregory S.; Bekelman, Justin E.

    2013-01-01

    Background This study compared the risk of fatal cerebrovascular accidents (CVA) in patients with early stage glottic larynx cancer receiving surgery or external beam radiation therapy (EBRT). Methods and Materials Using a competing risks survival analysis, we compared the risk of death due to CVA among patients with early stage glottic larynx cancer receiving surgery or EBRT in the SEER database. Results The cumulative incidence of fatal CVA at 15 years was higher in patients receiving EBRT (2.8 %; 95% CI 2.3%–3.4%) compared to surgery (1.5 %; 95% CI 0.8 %–2.3%, p= 0.024). In multivariable competing risks regression models, EBRT remained associated with an increased risk of fatal CVA compared to surgery (adjusted HR 1.75; 95% CI 1.04–2.96, p= 0.037). Conclusion Treatment of early stage glottic larynx cancer with EBRT was associated with a small increase in the risk of late fatal CVA events relative to surgery. PMID:23595858

  13. Treatment outcome and prognostic factor of CO2 laser cordectomy for early glottic cancer

    NASA Astrophysics Data System (ADS)

    Chung, Phil-Sang; Lee, Sang Joon

    2012-02-01

    Objectives: Laser cordectomy is very popular nowadays and become one of the treatments of choice for early glottis carcinoma. Transoral laser microsurgery has many advantages comparing conventional open surgery or radiation therapy. In this study, we examined the oncologic results of laser cordectomy for early glottic cancer and analyzed the prognostic impact on the survival of the several tumor-related and treatment-related factors. Methods: Patients who were diagnosed as early glottic squamous cell carcinoma, treated by laser cordectomy with curative intent were analyzed. Patients with preivous radiation therapy were included. From June 1988 to March 2005, 202 patients from five hospitals were analyzed (174 T1, 28 T2). Results: Five-year overall survival and disease-free survival were 98.4% and 84.9%. Twenty two patients developed local recurrence. Total laryngectomy was done in 6 patients and laryngeal preservation rate was 97%. Recurrence was higher in the patients with anterior commissure involvement (9/39) than without anterior commissure involvement (13/163). Recurrence was higher in T1b (4/15) than T1a (13/159). Previous radiation was also highly related to the recurrence (7/20 vs 15/182). Twenty patients with local recurrence after radiation therapy were treated by salvage laser cordectomy. Of them, 7 patients developed local recurrence and 5 year disease-free survival was 57%. Complication was rare with one case of hemorrhage. Tracheotomy was not necessary in all patients. Conclusions: Laser cordectomy for early glottic carcinoma showed high survival, laryngeal preservation rate and low complication rate. The prognostic factors were anterior commissure involvement, both vocal fold involvement and previous radiotherapy.

  14. Glottic and supraglottic pT3 squamous cell carcinoma: outcomes with transoral laser microsurgery.

    PubMed

    Pantazis, Dimitrios; Liapi, Georgia; Kostarelos, Dimitrios; Kyriazis, Georgios; Pantazis, Theodoros-Leonidas; Riga, Maria

    2015-08-01

    Patients diagnosed with T3 squamous cell laryngeal carcinomas are nowadays offered either organ-preserving surgical or non-surgical treatment, with the optimum approach remaining undefined. No direct comparison of organ-preserving therapeutical options, stratified by anatomical subsites is available in the literature. The aim of this study is to present institutional treatment outcomes for laser-assisted microsurgery (TLM) of laryngeal T3 squamous cell carcinomas and review the relevant literature. Sixty-four consecutive, previously untreated patients were evaluated. Twenty-four supraglottic and 19 glottic patients were treated with TLM and neck dissection, tumor exposure and postoperative upstaging of the tumors through pathology evaluation of the specimens being the only exclusion criteria. Five-year disease-specific survival and organ preservation rates for supraglottic carcinomas were both 91.7 %. The respective values for glottic carcinomas were 63.2 and 73.3 %. TLM-treated T3 supraglottic tumors seem to attribute better outcomes than T3 glottic tumors in terms of recurrence-free survival, organ preservation and local control (p = 0.01, <0.0001 and 0.01, respectively). The results of this study suggest that TLM-treated T3 supraglottic tumors have a good prognosis, substantially better than that of glottic tumors. A literature review, on the other hand, attributes to chemo-radiation-treated T3 supraglottic tumors a considerably poorer prognosis. Further studies of homogenous populations in terms of anatomical subsites are needed in order to reach a consensus regarding treatment of T3 laryngeal tumors.

  15. Phantom-to-clinic development of hypofractionated stereotactic body radiotherapy for early-stage glottic laryngeal cancer

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ding, Chuxiong; Chun, Stephen G.; Sumer, Baran D.

    The purpose of this study was to commission and clinically test a robotic stereotactic delivery system (CyberKnife, Sunnyvale, CA) to treat early-stage glottic laryngeal cancer. We enrolled 15 patients with cTis-T2N0M0 carcinoma of the glottic larynx onto an institutional review board (IRB)-approved clinical trial. Stereotactic body radiotherapy (SBRT) plans prescribed 45 Gy/10 fractions to the involved hemilarynx. SBRT dosimetry was compared with (1) standard carotid-sparing laryngeal intensity-modulated radiation therapy (IMRT) and (2) selective hemilaryngeal IMRT. Our results demonstrate that SBRT plans improved sparing of the contralateral arytenoid (mean 20.0 Gy reduction, p <0.001), ipsilateral carotid D{sub max} (mean 20.6 Gy reduction, p <0.001), contralateral carotidmore » D{sub max} (mean 28.1 Gy reduction, p <0.001), and thyroid D{sub mean} (mean 15.0 Gy reduction, p <0.001) relative to carotid-sparing IMRT. SBRT also modestly improved dose sparing to the contralateral arytenoid (mean 4.8 Gy reduction, p = 0.13) and spinal cord D{sub max} (mean 4.9 Gy reduction, p = 0.015) relative to selective hemilaryngeal IMRT plans. This “phantom-to-clinic” feasibility study confirmed that hypofractionated SBRT treatment for early-stage laryngeal cancer can potentially spare dose to adjacent normal tissues relative to current IMRT standards. Clinical efficacy and toxicity correlates continue to be collected through an ongoing prospective trial.« less

  16. Risk of Cerebrovascular Events in Elderly Patients After Radiation Therapy Versus Surgery for Early-Stage Glottic Cancer

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hong, Julian C.; Kruser, Tim J.; Gondi, Vinai

    Purpose: Comprehensive neck radiation therapy (RT) has been shown to increase cerebrovascular disease (CVD) risk in advanced-stage head-and-neck cancer. We assessed whether more limited neck RT used for early-stage (T1-T2 N0) glottic cancer is associated with increased CVD risk, using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Methods and Materials: We identified patients ≥66 years of age with early-stage glottic laryngeal cancer from SEER diagnosed from 1992 to 2007. Patients treated with combined surgery and RT were excluded. Medicare CPT codes for carotid interventions, Medicare ICD-9 codes for cerebrovascular events, and SEER data for stroke as the causemore » of death were collected. Similarly, Medicare CPT and ICD-9 codes for peripheral vascular disease (PVD) were assessed to serve as an internal control between treatment groups. Results: A total of 1413 assessable patients (RT, n=1055; surgery, n=358) were analyzed. The actuarial 10-year risk of CVD was 56.5% (95% confidence interval 51.5%-61.5%) for the RT cohort versus 48.7% (41.1%-56.3%) in the surgery cohort (P=.27). The actuarial 10-year risk of PVD did not differ between the RT (52.7% [48.1%-57.3%]) and surgery cohorts (52.6% [45.2%-60.0%]) (P=.89). Univariate analysis showed an increased association of CVD with more recent diagnosis (P=.001) and increasing age (P=.001). On multivariate Cox analysis, increasing age (P<.001) and recent diagnosis (P=.002) remained significantly associated with a higher CVD risk, whereas the association of RT and CVD remained not statistically significant (HR=1.11 [0.91-1.37,] P=.31). Conclusions: Elderly patients with early-stage laryngeal cancer have a high burden of cerebrovascular events after surgical management or RT. RT and surgery are associated with comparable risk for subsequent CVD development after treatment in elderly patients.« less

  17. Intraoperative narrow band imaging better delineates superficial resection margins during transoral laser microsurgery for early glottic cancer.

    PubMed

    Garofolo, Sabrina; Piazza, Cesare; Del Bon, Francesca; Mangili, Stefano; Guastini, Luca; Mora, Francesco; Nicolai, Piero; Peretti, Giorgio

    2015-04-01

    The high rate of positive margins after transoral laser microsurgery (TLM) remains a matter of debate. This study investigates the effect of intraoperative narrow band imaging (NBI) examination on the incidence of positive superficial surgical margins in early glottic cancer treated by TLM. Between January 2012 and October 2013, 82 patients affected by Tis-T1a glottic cancer were treated with TLM by type I or II cordectomies. Intraoperative NBI evaluation was performed using 0-degree and 70-degree rigid telescopes. Surgical specimens were oriented by marking the superior edge with black ink and sent to a dedicated pathologist. Comparison between the rate of positive superficial margins in the present cohort and in a matched historical control group treated in the same way without intraoperative NBI was calculated by chi-square test. At histopathological examination, all surgical margins were negative in 70 patients, whereas 7 had positive deep margins, 2 close, and 3 positive superficial margins. The rate of positive superficial margins was thus 3.6% in the present group and 23.7% in the control cohort (P<.001). Routine use of intraoperative NBI increases the accuracy of neoplastic superficial spreading evaluation during TLM for early glottic cancer. © The Author(s) 2014.

  18. The role of radiation therapy in resected T2 N0 esophageal cancer: a population-based analysis.

    PubMed

    Martin, Jeremiah T; Worni, Mathias; Zwischenberger, Joseph B; Gloor, Beat; Pietrobon, Ricardo; D'Amico, Thomas A; Berry, Mark F

    2013-02-01

    The prognosis of even early-stage esophageal cancer is poor. Because there is not a consensus on how to manage T2 N0 disease, we examined survival after resection of T2 N0 esophageal cancer, with or without radiation therapy. Patients who underwent resection for T2 N0 squamous cell carcinoma or adenocarcinoma of the mid or distal esophagus, with or without radiation therapy, were identified using the Surveillance, Epidemiology and End Results cancer registry from 1998 to 2008. The 5-year cancer-specific survival (CSS) and overall survival (OS) after resection alone and combined resection with radiation therapy were compared using the Kaplan-Meier approach, risk-adjusted Cox proportional hazard models, and competing risk models. The 5-year OS of 490 T2 N0 patients was 40.3% (95% confidence interval [CI], 35.2% to 45.4%). Surgical resection alone was used in 267 patients (54%) and combined therapy in 223 (46%). The 5-year OS was 38.6% (95% CI, 31.7% to 45.5%) in patients undergoing resection only and 42.3% (95% CI, 34.7% to 49.6%) for combined therapy (p = 0.48). No difference in OS was found, even after risk adjustment (hazard ratio [HR], 1.14; 95% CI, 0.87 to 1.48; p = 0.35). However, in landmark studies with left truncation for 3 and 6 months, resection only showed better OS than combined therapy (HR, 1.33; 95% CI, 1.01 to 1.75; p = 0.04 vs HR, 1.36; 95% CI, 1.01 to 1.83; p = 0.04, respectively). No such difference for CSS was detected, even for the landmark study after 6 months (HR, 1.16; 95% CI, 0.98 to 1.39, p = 0.09). Combining radiation therapy with esophagectomy did not result in improved outcomes compared with esophagectomy alone for patients with T2 N0 esophageal cancer in the Surveillance, Epidemiology and End Results database. Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  19. Risk of fatal cerebrovascular accidents after external beam radiation therapy for early-stage glottic laryngeal cancer.

    PubMed

    Swisher-McClure, Samuel; Mitra, Nandita; Lin, Alexander; Ahn, Peter; Wan, Fei; O'Malley, Bert; Weinstein, Gregory S; Bekelman, Justin E

    2014-05-01

    This study compared the risk of fatal cerebrovascular accidents (CVAs) in patients with early-stage glottic laryngeal cancer receiving surgery or external beam radiation therapy (EBRT). Using a competing risks survival analysis, we compared the risk of death because of CVA among patients with early-stage glottic laryngeal cancer receiving surgery or EBRT in the Surveillance, Epidemiology, and End Results (SEER) database. The cumulative incidence of fatal CVA at 15 years was higher in patients receiving EBRT (2.8%; 95% confidence interval [CI], 2.3% to 3.4%) compared to surgery (1.5%; 95% CI, 0.8% to 2.3%; p = .024). In multivariable competing risks regression models, EBRT remained associated with an increased risk of fatal CVA compared to surgery (adjusted hazard ratio [HR], 1.75; 95% CI, 1.04-2.96; p = .037). Treatment for early-stage glottic laryngeal cancer with EBRT was associated with a small increase in the risk of late fatal CVA events relative to surgery. Copyright © 2013 Wiley Periodicals, Inc.

  20. Comparative effectiveness of upfront esophagectomy versus induction chemoradiation in clinical stage T2N0 esophageal cancer: A decision analysis.

    PubMed

    Semenkovich, Tara R; Panni, Roheena Z; Hudson, Jessica L; Thomas, Theodore; Elmore, Leisha C; Chang, Su-Hsin; Meyers, Bryan F; Kozower, Benjamin D; Puri, Varun

    2018-05-01

    We compared the effectiveness of upfront esophagectomy versus induction chemoradiation followed by esophagectomy for overall survival in patients with clinical T2N0 (cT2N0) esophageal cancer. We also assessed the influence of the diagnostic uncertainty of endoscopic ultrasound on the expected benefit of chemoradiation. We created a decision analysis model representing 2 treatment strategies for cT2N0 esophageal cancer: upfront esophagectomy that may be followed by adjuvant therapy for upstaged patients and induction chemoradiation for all patients with cT2N0 esophageal cancer followed by esophagectomy. Parameter values within the model were obtained from published data, and median survival for pathologic subgroups was derived from the National Cancer Database. In sensitivity analyses, staging uncertainty of endoscopic ultrasound was introduced by varying the probability of pathologic upstaging. The baseline model showed comparable median survival for both strategies: 48.3 months for upfront esophagectomy versus 45.9 months for induction chemoradiation and surgery. The sensitivity analysis demonstrated induction chemoradiation was beneficial, with probability of upstaging > 48.1%, which is within the published range of 32% to 65% probability of pathologic upstaging after cT2N0 diagnosis. The presence of any of 3 key variables (size larger than 3 cm, high grade, or lymphovascular invasion) was associated with > 48.1% risk of upstaging, thus conferring a survival advantage to induction chemoradiation. The optimal treatment strategy for cT2N0 esophageal cancer depends on the accuracy of endoscopic ultrasound staging. High-risk features that confer increased probability of upstaging can inform clinical decision making to recommend induction chemoradiation for select cT2N0 patients. Copyright © 2018 The American Association for Thoracic Surgery. All rights reserved.

  1. Role of postoperative radiation therapy (PORT) in pT1-T2 N0 deep tongue cancers.

    PubMed

    Gokavarapu, Sandhya; Parvataneni, Nagendra; Rao S, L M Chandrasekhara; Reddy, Rammohan; Raju, K V V N; Chander, Ravi

    2015-12-01

    Carcinoma of tongue is associated with a high risk of occult metastasis and mortality despite early-stage detection and therapy; the critical tumor thickness at which this risk increases has been demonstrated as 4 mm or greater. There are no sufficient data in the published literature to evaluate the role of postoperative radiation therapy (PORT) in the treatment of pT1-T2 N0 oral tongue cancers with depth of invasion 4 mm or greater. Historical cohorts of patients with primary pT1-T2 N0 oral tongue cancer of depth of invasion 4 mm or greater treated surgically from January 2010 to December 2012 were included in the study, and negative margins on initial resection were filtered. Locoregional recurrence and death were analyzed among the patients who received PORT and those who did not. A total of 103 patients fulfilled the above-mentioned criteria, with 62 patients receiving PORT and 41 patients not receiving PORT; median period of follow-up was 41.3 months. Logistic and Cox regression models showed no significant difference in locoregional recurrences (P = .078) and survival (P = .339) between patients who received PORT and those who did not receive PORT. PORT did not influence survival of patients with stage I and stage II deep tongue cancers, with 4 mm or greater tumor invasion depth. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Evaluation of the reliability of clinical staging of T2 N0 esophageal cancer: a review of the Society of Thoracic Surgeons database.

    PubMed

    Crabtree, Traves D; Kosinski, Andrzej S; Puri, Varun; Burfeind, William; Bharat, Ankit; Patterson, G Alexander; Hofstetter, Wayne; Meyers, Bryan F

    2013-08-01

    Clinical staging of esophageal cancer has improved with positron-emission tomography/computed tomography and endoscopic ultrasound imaging. Despite such progress, small single-center studies have questioned the reliability of clinical staging of T2 N0 esophageal cancer. This study broadly examines the adequacy of clinical staging of T2 N0 disease using The Society of Thoracic Surgeons database. We retrospectively studied 810 clinical stage T2 N0 patients from 2002 to 2011, with 58 excluded because of incomplete pathologic staging data. Clinical stage, pathologic stage, and preoperative characteristics were recorded. Logistic regression analysis was used to identify factors associated with upstaging at the time of surgical intervention. Among 752 clinical stage T2 N0 patients, 270 (35.9%) received induction therapy before the operation. Of 482 patients who went directly to surgical intervention, 132 (27.4%) were confirmed as pathologic T2 N0, 125 (25.9%) were downstaged (ie, T0-1 N0), and 225 (46.7%) were upstaged at the operation (T3-4 N0 or Tany N1-3). Exclusive tumor upstaging (ie, pathologic T3-4 N0) accounted for 41 patients (18.2%), whereas exclusive nodal upstaging (ie, pathological T1-2 N1-3) accounted for 100 (44.5%). Combined tumor and nodal upstaging (ie, pathological T3-4 N1-3) accounted for 84 patients (37.3%). Among patients who received induction therapy, 103 (38.1%) were upstaged vs 225 (46.7%) without induction therapy (p = 0.026). Comparing the induction therapy group and the primary surgical group, postoperative 30-day mortality (3.7% vs 3.7%, p > 0.99) and morbidity (46.3% vs 45%, p = 0.76) were similar. Despite advances in staging techniques, clinical staging of T2 N0 esophageal cancer remains unreliable. Recognizing T2 N0 as a threshold for induction therapy in esophageal cancer, many surgeons have opted to treat T2 N0 disease with induction therapy, even though one-quarter of these patients will be pathologic T1 N0. Although this study

  3. Adjuvant Chemotherapy for Patients with T2N0M0 NSCLC.

    PubMed

    Morgensztern, Daniel; Du, Lingling; Waqar, Saiama N; Patel, Aalok; Samson, Pamela; Devarakonda, Siddhartha; Gao, Feng; Robinson, Cliff G; Bradley, Jeffrey; Baggstrom, Maria; Masood, Ashiq; Govindan, Ramaswamy; Puri, Varun

    2016-10-01

    Adjuvant chemotherapy improves survival in patients with completely resected stage II and III NSCLC. However, its role in patients with stage IB NSCLC disease remains unclear. We evaluated the role of adjuvant chemotherapy in a large data set of patients with completely resected T2N0M0 NSCLC. Patients with pathologic stage T2N0M0 NSCLC who underwent complete (R0) resection between 2004 and 2011 were identified from the National Cancer Data Base and classified into four groups based on tumor size: 3.1 to 3.9 cm, 4 to 4.9 cm, 5 to 5.9 cm, and 6 to 7 cm. Patients who died within 1 month after their operation were excluded. Survival curves were estimated by the Kaplan-Meier product-limit method and compared by log-rank test. Among the 25,267 patients who met the inclusion criteria, there were 4996 (19.7%) who received adjuvant chemotherapy. Adjuvant chemotherapy was associated with improved median and 5-year overall survival compared with observation for all tumor size groups. In patients with T2 tumors smaller than 4 cm, adjuvant chemotherapy was associated with improved median and 5-year overall survival in univariate (101.6 versus 68.2 months [67% versus 55%], hazard ratio [HR] = 0.66, 95% confidence interval [CI]: 0.61-0.72, p < 0.0001) and multivariable analysis (HR = 0.77, 95% CI: 0.70-0.83, p < 0.001) as well as propensity-matched score (101.6 versus 78.9 months [68% versus 60%], HR = 0.75, 95% CI: 0.70-0.86; p < 0.0001). In patients with completely resected T2N0M0, adjuvant chemotherapy is associated with improved survival in all tumor size groups. The benefit in patients with tumors smaller than 4 cm strongly suggests a role for chemotherapy in this patient population and counters its current status as an exclusion criteria for adjuvant trials. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

  4. Elective Inguinal Node Irradiation in Early-Stage T2N0 Anal Cancer: Prognostic Impact on Locoregional Control

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zilli, Thomas, E-mail: Thomas.Zilli@hcuge.ch; Betz, Michael; Radiation Oncology Institute, Hirslanden Lausanne, Lausanne

    2013-09-01

    Purpose: To evaluate the influence of elective inguinal node radiation therapy (INRT) on locoregional control (LRC) in patients with early-stage T2N0 anal cancer treated conservatively with primary RT. Methods and Materials: Between 1976 and 2008, 116 patients with T2 node-negative anal cancer were treated curatively with RT alone (n=48) or by combined chemoradiation therapy (CRT) (n=68) incorporating mitomycin C and 5-fluorouracil. Sixty-four percent of the patients (n=74) received elective INRT. Results: Over a median follow-up of 69 months (range, 4-243 months), 97 (84%) and 95 patients (82%) were locally and locoregionally controlled, respectively. Rates for 5-year actuarial local control, LRC,more » cancer-specific, and overall survival for the entire population were 81.7% ± 3.8%, 79.2% ± 4.1%, 91.1% ± 3.0%, and 72.1% ± 4.5%, respectively. The overall 5-year inguinal relapse-free survival was 92.3% ± 2.9%. Isolated inguinal recurrence occurred in 2 patients (4.7%) treated without INRT, whereas no groin relapse was observed in those treated with INRT. The 5-year LRC rates for patients treated with and without INRT and with RT alone versus combined CRT were 80.1% ± 5.0% versus 77.8% ± 7.0% (P=.967) and 71.0% ± 7.2% versus 85.4% ± 4.5% (P=.147), respectively. A trend toward a higher rate of grade ≥3 acute toxicity was observed in patients treated with INRT (53% vs 31%, P=.076). Conclusions: In cases of node-negative T2 anal cancer, the inguinal relapse rate remains relatively low with or without INRT. The role of INRT in the treatment of early-stage anal carcinoma needs to be investigated in future prospective trials.« less

  5. Definitive hypofractionated radiotherapy for early glottic carcinoma: experience of 55Gy in 20 fractions.

    PubMed

    Ermiş, Ekin; Teo, Mark; Dyker, Karen E; Fosker, Chris; Sen, Mehmet; Prestwich, Robin Jd

    2015-09-23

    A wide variety of fractionation schedules have been employed for the treatment of early glottic cancer. The aim is to report our 10-year experience of using hypofractionated radiotherapy with 55Gy in 20 fractions at 2.75Gy per fraction. Patients treated between 2004 and 2013 with definitive radiotherapy to a dose of 55Gy in 20 fractions over 4 weeks for T1/2 N0 squamous cell carcinoma of the glottis were retrospectively identified. Patients with prior therapeutic minor surgery (eg. laser stripping, cordotomy) were included. The probabilities of local control, ultimate local control (including salvage surgery), regional control, cause specific survival (CSS) and overall survival (OS) were calculated. One hundred thirty-two patients were identified. Median age was 65 years (range 33-89). Median follow up was 72 months (range 7-124). 50 (38 %), 18 (14 %) and 64 (48 %) of patients had T1a, T1b and T2 disease respectively. Five year local control and ultimate local control rates were: overall - 85.6 % and 97.3 % respectively, T1a - 91.8 % and 100 %, T1b - 81.6 and 93.8 %, and T2 - 80.9 % and 95.8 %. Five year regional control, CSS and OS rates were 95.4 %, 95.7 % and 78.8 % respectively. There were no significant associations of covariates (e.g. T-stage, extent of laryngeal extension, histological grade) with local control on univariate analysis. Only increasing age and transglottic extension in T2 disease were significantly associated with overall survival (both p <0.01). Second primary cancers developed in 17 % of patients. 13 (9.8 %) of patients required enteral tube feeding support during radiotherapy; no patients required long term enteral nutrition. One patient required a tracheostomy due to a non-functioning larynx on long term follow up. Hypofractionated radiation therapy with a dose of 55Gy in 20 fractions for early stage glottic cancer provides high rates of local control with acceptable toxicity.

  6. Results of Neoadjuvant Short-Course Radiation Therapy Followed by Transanal Endoscopic Microsurgery for T1-T2 N0 Extraperitoneal Rectal Cancer

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Arezzo, Alberto, E-mail: alberto.arezzo@unito.it; Arolfo, Simone; Allaix, Marco Ettore

    Purpose: This study was undertaken to assess the short-term outcomes of neoadjuvant short-course radiation therapy (SCRT) followed by transanal endoscopic microsurgery (TEM) for T1-T2 N0 extraperitoneal rectal cancer. Recent studies suggest that neoadjuvant radiation therapy followed by TEM is safe and has results similar to those with abdominal rectal resection for the treatment of extraperitoneal early rectal cancer. Methods and Materials: We planned a prospective pilot study including 25 consecutive patients with extraperitoneal T1-T2 N0 M0 rectal adenocarcinoma undergoing SCRT followed by TEM 4 to 10 weeks later (SCRT-TEM). Safety, efficacy, and acceptability of this treatment modality were compared with historicalmore » groups of patients with similar rectal cancer stage and treated with long-course radiation therapy (LCRT) followed by TEM (LCRT-TEM), TEM alone, or laparoscopic rectal resection with total mesorectal excision (TME) at our institution. Results: The study was interrupted after 14 patients underwent SCRT of 25 Gy in 5 fractions followed by TEM. Median time between SCRT and TEM was 7 weeks (range: 4-10 weeks). Although no preoperative complications occurred, rectal suture dehiscence was observed in 7 patients (50%) at 4 weeks follow-up, associated with an enterocutaneous fistula in the sacral area in 2 cases. One patient required a colostomy. Quality of life at 1-month follow-up, according to European Organization for Research and Treatment of Cancer QLQ-C30 survey score, was significantly worse in SCRT-TEM patients than in LCRT-TEM patients (P=.0277) or TEM patients (P=.0004), whereas no differences were observed with TME patients (P=.604). At a median follow-up of 10 months (range: 6-26 months), we observed 1 (7%) local recurrence at 6 months that was treated with abdominoperineal resection. Conclusions: SCRT followed by TEM for T1-T2 N0 rectal cancer is burdened by a high rate of painful dehiscence of the suture line and

  7. CO2 laser versus cold steel margin analysis following endoscopic excision of glottic cancer

    PubMed Central

    2014-01-01

    Objective To compare the suitability of CO2 laser with steel instruments for margin excision in transoral laser microsurgery. Methods Prospective randomized blinded study. Patients with glottic cancer undergoing laser resection were randomized to margin excision by either steel instruments or CO2 laser. Margins were analyzed for size, interpretability and degree of artifact by a pathologist who was blinded to technique. Results 45 patients were enrolled in the study with 226 total margins taken. 39 margins taken by laser had marked artifact and 0 were uninterpretable. 20 margins taken by steel instruments had marked artifact, and 2 were uninterpretable. Controlling for margin size, the laser technique was associated with increasing degrees of margin artifact (p = 0.210), but there was no difference in crude rates of uninterpretability (p = 0.24). Conclusion Laser margin excision is associated with a greater degree of artifact than steel instrument excision, but was not associated with higher rate of uninterpretability. PMID:24502856

  8. Role of Adjuvant Chemotherapy in ypT0-2N0 Patients Treated with Preoperative Chemoradiation Therapy and Radical Resection for Rectal Cancer

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Park, In Ja; Kim, Dae Yong; Kim, Hee Cheol

    2015-07-01

    Objective: To explore the role of adjuvant chemotherapy for patients with ypT0-2N0 rectal cancer treated by preoperative chemoradiation therapy (PCRT) and radical resection. Patients and Methods: A national consortium of 10 institutions was formed, and patients with ypT0-2N0 mid- and low-rectal cancer after PCRT and radical resection from 2004 to 2009 were included. Patients were categorized into 2 groups according to receipt of additional adjuvant chemotherapy: Adj CTx (+) versus Adj CTx (−). Propensity scores were calculated and used to perform matched and adjusted analyses comparing relapse-free survival (RFS) between treatment groups while controlling for potential confounding. Results: A totalmore » of 1016 patients, who met the selection criteria, were evaluated. Of these, 106 (10.4%) did not receive adjuvant chemotherapy. There was no overall improvement in 5-year RFS as a result of adjuvant chemotherapy [91.6% for Adj CTx (+) vs 87.5% for Adj CTx (−), P=.18]. There were no differences in 5-year local recurrence and distant metastasis rate between the 2 groups. In patients who show moderate, minimal, or no regression in tumor regression grade, however, possible association of adjuvant chemotherapy with RFS would be considered (hazard ratio 0.35; 95% confidence interval 0.14-0.88; P=.03). Cox regression analysis after propensity score matching failed to show that addition of adjuvant chemotherapy was associated with improved RFS (hazard ratio 0.81; 95% confidence interval 0.39-1.70; P=.58). Conclusions: Adjuvant chemotherapy seemed to not influence the RFS of patients with ypT0-2N0 rectal cancer after PCRT followed by radical resection. Thus, the addition of adjuvant chemotherapy needs to be weighed against its oncologic benefits.« less

  9. Role of Adjuvant Chemotherapy in ypT0-2N0 Patients Treated with Preoperative Chemoradiation Therapy and Radical Resection for Rectal Cancer.

    PubMed

    Park, In Ja; Kim, Dae Yong; Kim, Hee Cheol; Kim, Nam Kyu; Kim, Hyeong-Rok; Kang, Sung-Bum; Choi, Gyu-Seog; Lee, Kang Young; Kim, Seon-Hahn; Oh, Seung Taek; Lim, Seok-Byung; Kim, Jin Cheon; Oh, Jae Hwan; Kim, Sun Young; Lee, Woo Yong; Lee, Jung Bok; Yu, Chang Sik

    2015-07-01

    To explore the role of adjuvant chemotherapy for patients with ypT0-2N0 rectal cancer treated by preoperative chemoradiation therapy (PCRT) and radical resection. A national consortium of 10 institutions was formed, and patients with ypT0-2N0 mid- and low-rectal cancer after PCRT and radical resection from 2004 to 2009 were included. Patients were categorized into 2 groups according to receipt of additional adjuvant chemotherapy: Adj CTx (+) versus Adj CTx (-). Propensity scores were calculated and used to perform matched and adjusted analyses comparing relapse-free survival (RFS) between treatment groups while controlling for potential confounding. A total of 1016 patients, who met the selection criteria, were evaluated. Of these, 106 (10.4%) did not receive adjuvant chemotherapy. There was no overall improvement in 5-year RFS as a result of adjuvant chemotherapy [91.6% for Adj CTx (+) vs 87.5% for Adj CTx (-), P=.18]. There were no differences in 5-year local recurrence and distant metastasis rate between the 2 groups. In patients who show moderate, minimal, or no regression in tumor regression grade, however, possible association of adjuvant chemotherapy with RFS would be considered (hazard ratio 0.35; 95% confidence interval 0.14-0.88; P=.03). Cox regression analysis after propensity score matching failed to show that addition of adjuvant chemotherapy was associated with improved RFS (hazard ratio 0.81; 95% confidence interval 0.39-1.70; P=.58). Adjuvant chemotherapy seemed to not influence the RFS of patients with ypT0-2N0 rectal cancer after PCRT followed by radical resection. Thus, the addition of adjuvant chemotherapy needs to be weighed against its oncologic benefits. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Clinical and Economic Evaluation of Treatment Strategies for T1N0 Anal Canal Cancer.

    PubMed

    Deshmukh, Ashish A; Zhao, Hui; Das, Prajnan; Chiao, Elizabeth Y; You, Yi-Qian Nancy; Franzini, Luisa; Lairson, David R; Swartz, Michael D; Giordano, Sharon H; Cantor, Scott B

    2018-07-01

    A comparative assessment of treatment alternatives for T1N0 anal canal cancer has never been conducted. We compared the outcomes associated with the treatment alternatives-chemoradiotherapy (CRT), radiotherapy (RT), and surgery or ablation techniques (surgery/ablation)-for T1N0 anal canal cancer. This retrospective cohort study was conducted using the Surveillance, Epidemiology and End Results (SEER) registries linked with Medicare longitudinal data (SEER-Medicare database). Analysis included 190 patients who were treated for T1N0 anal canal cancer using surgery/ablation (n=44), RT (n=50), or CRT (n=96). The outcomes were reported in terms of survival and hazards ratios using Kaplan-Meier and Cox proportional hazards modeling, respectively; lifetime costs; and cost-effectiveness measured in terms of incremental cost-effectiveness ratio, that is, the ratio of the difference in costs between the 2 alternatives to the difference in effectiveness between the same 2 alternatives. There was no significant difference in the survival duration between the treatment groups as predicted by the Kaplan-Meier curves. After adjusting for patient characteristics and propensity score, the hazard ratio of death for the patients who received CRT compared with surgery/ablation was 1.742 (95% confidence interval, 0.793-3.829) and RT was 2.170 (95% confidence interval, 0.923-5.101); however, the relationship did not reach statistical significance. Surgery/ablation resulted in lower lifetime cost than RT or CRT. The incremental cost-effectiveness ratio associated with CRT compared with surgery/ablation was $142,883 per life year gained. There was no statistically significant difference in survival among the treatment alternatives for T1N0 anal canal cancer. Given that surgery/ablation costs less than RT or CRT and might be cost-effective compared with RT and CRT, it is crucial to explore this finding further in this era of limited health care resources.

  11. Early-stage Node-negative (T1-T2N0) Anal Cancer Treated with Simultaneous Integrated Boost Radiotherapy and Concurrent Chemotherapy.

    PubMed

    Franco, Pierfrancesco; Arcadipane, Francesca; Ragona, Riccardo; Mistrangelo, Massimiliano; Cassoni, Paola; Rondi, Nadia; Morino, Mario; Racca, Patrizia; Ricardi, Umberto

    2016-04-01

    To report clinical outcomes of a consecutive series of patients with early-stage (T1-T1N0) anal cancer treated with intensity-modulated radiotherapy (IMRT) and a simultaneous integrated boost (SIB) approach similarly to the RTOG 05-29 trial. A cohort of 43 patients underwent SIB-IMRT employing a schedule consisting of 50.4 Gy/28 fractions to the gross tumor volume and 42 Gy/28 fractions to the elective nodal volumes for cT1N0 cases, and 54 Gy/30 fractions and 45 Gy/30 fractions to the same volumes for cT2N0 cases. Chemotherapy was administered concurrently following Nigro's regimen. The primary endpoint was colostomy-free survival (CFS). Secondary endpoints were locoregional control (LRC), disease-free (DFS), cancer-specific (CSS) and overall (OS) survival. Median follow-up was 39.7 months. The actuarial 3-year CFS was 79.4% [95% confidence interval (CI)=61.4-89.7%]. Actuarial 3-year OS and CSS were 90.8% (95% CI=74.1-96.9%) and 93.8% (95% CI=77.3-98.4%), while DFS was 75.5% (95% CI=56.4-87.1%). Actuarial 3-year LRC was 86.1% (95% CI=69.6-94%). On multivariate analysis, tumor size >3 cm showed a trend towards significance in predicting CFS [hazard ratio (HR)=8.6, 95% CI=84.7-88.1%; p=0.069]. Maximum detected adverse events included: skin (G3): 18%; gastrointestinal tract (G2): 67%; genitourinary tract (G3): 3%; genitalia (G2): 30%; anemia (G2): 7%; leukopenia (G3): 26%, leukopenia (G4):7%; neutropenia (G3): 15%; neutropenia (G4): 12%; thrombocytopenia (G3): 9%. Our clinical results support the use of SIB-IMRT in the combined modality treatment of patients with anal cancer. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  12. Dosimetric comparison of helical tomotherapy, intensity-modulated radiation therapy, volumetric-modulated arc therapy, and 3-dimensional conformal therapy for the treatment of T1N0 glottic cancer

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ekici, Kemal, E-mail: drkemal06@hotmail.com; Pepele, Eda K.; Yaprak, Bahaddin

    2016-01-01

    Various radiotherapy planning methods for T1N0 laryngeal cancer have been proposed to decrease normal tissue toxicity. We compare helical tomotherapy (HT), linac-based intensity-modulated radiation therapy (IMRT), volumetric-modulated arc therapy (VMAT), and 3-D conformal radiotherapy (3D-CRT) techniques for T1N0 laryngeal cancer. Overall, 10 patients with T1N0 laryngeal cancer were selected and evaluated. Furthermore, 10 radiotherapy treatment plans have been created for all 10 patients, including HT, IMRT, VMAT, and 3D-CRT. IMRT, VMAT, and HT plans vs 3D-CRT plans consistently provided superior planning target volume (PTV) coverage. Similar target coverage was observed between the 3 IMRT modalities. Compared with 3D-CRT, IMRT, HT,more » and VMAT significantly reduced the mean dose to the carotid arteries. VMAT resulted in the lowest mean dose to the submandibular and thyroid glands. Compared with 3D-CRT, IMRT, HT, and VMAT significantly increased the maximum dose to the spinal cord It was observed that the 3 IMRT modalities studied showed superior target coverage with less variation between each plan in comparison with 3D-CRT. The 3D-CRT plans performed better at the D{sub max} of the spinal cord. Clinical investigation is warranted to determine if these treatment approaches would translate into a reduction in radiation therapy–induced toxicities.« less

  13. A screening questionnaire for voice problems after treatment of early glottic cancer

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gogh, Christine D.L. van; Verdonck-de Leeuw, Irma M.; Boon-Kamma, Brigitte A.

    Purpose: After treatment for early glottic cancer, a considerable number of patients end up with voice problems interfering with daily life activities. A 5-item screening questionnaire was designed for detection of voice impairment. The purpose of this study is to assess psychometric properties of this questionnaire in clinical practice. Methods and Materials: The questionnaire was completed by 110 controls without voice complaints and 177 patients after radiotherapy or laser surgery for early glottic cancer. Results: Based on normative data of the controls, a score of 5 or less on at least 1 of the 5 questions was considered to statemore » overall voice impairment. Reliability of the questionnaire proved to be good. Voice impairment was reported in 44% of the patients treated with radiotherapy vs. 29% of the patients treated with endoscopic laser surgery. Conclusions: The questionnaire proved to be a reliable, valid, and feasible method to detect voice impairment in daily life. The questionnaire is easy to fill in, and interpretation is straightforward. It is useful for both radiation oncologists and otorhinolaryngologists in their follow-up of patients treated for early glottic cancer.« less

  14. High-resolution T2-weighted cervical cancer imaging: a feasibility study on ultra-high-field 7.0-T MRI with an endorectal monopole antenna.

    PubMed

    Hoogendam, Jacob P; Kalleveen, Irene M L; de Castro, Catalina S Arteaga; Raaijmakers, Alexander J E; Verheijen, René H M; van den Bosch, Maurice A A J; Klomp, Dennis W J; Zweemer, Ronald P; Veldhuis, Wouter B

    2017-03-01

    We studied the feasibility of high-resolution T 2 -weighted cervical cancer imaging on an ultra-high-field 7.0-T magnetic resonance imaging (MRI) system using an endorectal antenna of 4.7-mm thickness. A feasibility study on 20 stage IB1-IIB cervical cancer patients was conducted. All underwent pre-treatment 1.5-T MRI. At 7.0-T MRI, an external transmit/receive array with seven dipole antennae and a single endorectal monopole receive antenna were used. Discomfort levels were assessed. Following individualised phase-based B 1 + shimming, T 2 -weighted turbo spin echo sequences were completed. Patients had stage IB1 (n = 9), IB2 (n = 4), IIA1 (n = 1) or IIB (n = 6) cervical cancer. Discomfort (ten-point scale) was minimal at placement and removal of the endorectal antenna with a median score of 1 (range, 0-5) and 0 (range, 0-2) respectively. Its use did not result in adverse events or pre-term session discontinuation. To demonstrate feasibility, T 2 -weighted acquisitions from 7.0-T MRI are presented in comparison to 1.5-T MRI. Artefacts on 7.0-T MRI were due to motion, locally destructive B 1 interference, excessive B 1 under the external antennae and SENSE reconstruction. High-resolution T 2 -weighted 7.0-T MRI of stage IB1-IIB cervical cancer is feasible. The addition of an endorectal antenna is well tolerated by patients. • High resolution T 2 -weighted 7.0-T MRI of the inner female pelvis is challenging • We demonstrate a feasible approach for T 2 -weighted 7.0-T MRI of cervical cancer • An endorectal monopole receive antenna is well tolerated by participants • The endorectal antenna did not lead to adverse events or session discontinuation.

  15. [The application of full thicknes skin graft inpartial laryngectomy for glottic carcinoma].

    PubMed

    Fu, Y G; Sun, D Z; Yang, P Z; Chen, Y L; Chen, Z P; Yang, Z K

    2016-08-05

    Objective: The aim of this study is to explore the experience and advantages of the application of full thicknes skin graft in glottic carcinoma.partial laryngectomy for glottic carcinoma. Method: One hundred and forty-three patients with glottic cancer were treated with partial laryngectomy.Among those,78 cases were repaired with full-thickness skin graft and 65 cases were repaired with sternohyoid muscular fasciae.Compared the time of extubation and the formation of granulation in laryngeal cavity after operation between the two groups. Result: In the group of full-thickness skin graft,the mean time of decannulation was 6.8 days,5 cases with growth of granulation after operation.In other group,the mean time of decannulation was 10.7 days,16 cases with growth of granulation after operation.The mean time of decannulation( t =-4.739, P <0.01) and the growth of granulation(χ²=9.379, P <0.01) are significantly different between the two groups.No laryngostenosis was found in all patients. Conclusion: The application of full-thicknes skin graft in partial laryngectomy for glottic carcinoma.can shortthe time of extubation and reduce the formation of granulation. Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.

  16. p53 predictive value for pT1-2 N0 disease at radical cystectomy.

    PubMed

    Shariat, Shahrokh F; Lotan, Yair; Karakiewicz, Pierre I; Ashfaq, Raheela; Isbarn, Hendrik; Fradet, Yves; Bastian, Patrick J; Nielsen, Matthew E; Capitanio, Umberto; Jeldres, Claudio; Montorsi, Francesco; Müller, Stefan C; Karam, Jose A; Heukamp, Lukas C; Netto, George; Lerner, Seth P; Sagalowsky, Arthur I; Cote, Richard J

    2009-09-01

    Approximately 15% to 30% of patients with pT1-2N0M0 urothelial carcinoma of the bladder experience disease progression despite radical cystectomy with curative intent. We determined whether p53 expression would improve the prediction of disease progression after radical cystectomy for pT1-2N0M0 UCB. In a multi-institutional retrospective cohort we identified 324 patients with pT1-2N0M0 urothelial carcinoma of the bladder who underwent radical cystectomy. Analysis focused on a testing cohort of 272 patients and an external validation of 52. Competing risks regression models were used to test the association of variables with cancer specific mortality after accounting for nonbladder cancer caused mortality. In the testing cohort 91 patients (33.5%) had altered p53 expression (p53alt). On multivariate competing risks regression analysis altered p53 achieved independent status for predicting disease recurrence and cancer specific mortality (each p <0.001). Adding p53 increased the accuracy of multivariate competing risks regression models predicting recurrence and cancer specific mortality by 5.7% (62.0% vs 67.7%) and 5.4% (61.6% vs 67.0%), respectively. Alterations in p53 represent a highly promising marker of disease recurrence and cancer specific mortality after radical cystectomy for urothelial carcinoma of the bladder. Analysis confirmed previous findings and showed that considering p53 can result in substantial accuracy gains relative to the use of standard predictors. The value and the level of the current evidence clearly exceed previous proof of the independent predictor status of p53 for predicting recurrence and cancer specific mortality.

  17. Single Vocal Cord Irradiation: Image Guided Intensity Modulated Hypofractionated Radiation Therapy for T1a Glottic Cancer: Early Clinical Results

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Al-Mamgani, Abrahim, E-mail: a.almamgani@nki.nl; Kwa, Stefan L.S.; Tans, Lisa

    2015-10-01

    Purpose: To report, from a retrospective analysis of prospectively collected data, on the feasibility, outcome, toxicity, and voice-handicap index (VHI) of patients with T1a glottic cancer treated by a novel intensity modulated radiation therapy technique developed at our institution to treat only the involved vocal cord: single vocal cord irradiation (SVCI). Methods and Materials: Thirty patients with T1a glottic cancer were treated by means of SVCI. Dose prescription was set to 16 × 3.63 Gy (total dose 58.08 Gy). The clinical target volume was the entire vocal cord. Setup verification was done by means of an online correction protocol using cone beam computed tomography. Datamore » for voice quality assessment were collected prospectively at baseline, end of treatment, and 4, 6, and 12 weeks and 6, 12, and 18 months after treatment using VHI questionnaires. Results: After a median follow-up of 30 months (range, 7-50 months), the 2-year local control and overall survival rates were 100% and 90% because no single local recurrence was reported and 3 patients died because of comorbidity. All patients have completed the intended treatment schedule; no treatment interruptions and no grade 3 acute toxicity were reported. Grade 2 acute dermatitis or dysphagia was reported in only 5 patients (17%). No serious late toxicity was reported; only 1 patient developed temporary grade 2 laryngeal edema, and responded to a short-course of corticosteroid. The VHI improved significantly, from 33.5 at baseline to 9.5 and 10 at 6 weeks and 18 months, respectively (P<.001). The control group, treated to the whole larynx, had comparable local control rates (92.2% vs 100%, P=.24) but more acute toxicity (66% vs 17%, P<.0001) and higher VHI scores (23.8 and 16.7 at 6 weeks and 18 months, respectively, P<.0001). Conclusion: Single vocal cord irradiation is feasible and resulted in maximal local control rate at 2 years. The deterioration in VHI scores was slight and

  18. [Prognostic differences of phenotypes in pT1-2N0 invasive breast cancer: a large cohort study with cluster analysis].

    PubMed

    Wang, Z; Wang, W H; Wang, S L; Jin, J; Song, Y W; Liu, Y P; Ren, H; Fang, H; Tang, Y; Chen, B; Qi, S N; Lu, N N; Li, N; Tang, Y; Liu, X F; Yu, Z H; Li, Y X

    2016-06-23

    To find phenotypic subgroups of patients with pT1-2N0 invasive breast cancer by means of cluster analysis and estimate the prognosis and clinicopathological features of these subgroups. From 1999 to 2013, 4979 patients with pT1-2N0 invasive breast cancer were recruited for hierarchical clustering analysis. Age (≤40, 41-70, 70+ years), size of primary tumor, pathological type, grade of differentiation, microvascular invasion, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) were chosen as distance metric between patients. Hierarchical cluster analysis was performed using Ward's method. Cophenetic correlation coefficient (CPCC) and Spearman correlation coefficient were used to validate clustering structures. The CPCC was 0.603. The Spearman correlation coefficient was 0.617 (P<0.001), which indicated a good fit of hierarchy to the data. A twelve-cluster model seemed to best illustrate our patient cohort. Patients in cluster 5, 9 and 12 had best prognosis and were characterized by age >40 years, smaller primary tumor, lower histologic grade, positive ER and PR status, and mainly negative HER-2. Patients in the cluster 1 and 11 had the worst prognosis, The cluster 1 was characterized by a larger tumor, higher grade and negative ER and PR status, while the cluster 11 was characterized by positive microvascular invasion. Patients in other 7 clusters had a moderate prognosis, and patients in each cluster had distinctive clinicopathological features and recurrent patterns. This study identified distinctive clinicopathologic phenotypes in a large cohort of patients with pT1-2N0 breast cancer through hierarchical clustering and revealed different prognosis. This integrative model may help physicians to make more personalized decisions regarding adjuvant therapy.

  19. Association between US features of primary tumor and axillary lymph node metastasis in patients with clinical T1-T2N0 breast cancer.

    PubMed

    Bae, Min Sun; Shin, Sung Ui; Song, Sung Eun; Ryu, Han Suk; Han, Wonshik; Moon, Woo Kyung

    2018-04-01

    Background Most patients with early-stage breast cancer have clinically negative lymph nodes (LNs). However, 15-20% of patients have axillary nodal metastasis based on the sentinel LN biopsy. Purpose To assess whether ultrasound (US) features of a primary tumor are associated with axillary LN metastasis in patients with clinical T1-T2N0 breast cancer. Material and Methods This retrospective study included 138 consecutive patients (median age = 51 years; age range = 27-78 years) who underwent breast surgery with axillary LN evaluation for clinically node-negative T1-T2 breast cancer. Three radiologists blinded to the axillary surgery results independently reviewed the US images. Tumor distance from the skin and distance from the nipple were determined based on the US report. Association between US features of a breast tumor and axillary LN metastasis was assessed using a multivariate logistic regression model after controlling for clinicopathologic variables. Results Of the 138 patients, 28 (20.3%) had nodal metastasis. At univariate analysis, tumor distance from the skin ( P = 0.019), tumor size on US ( P = 0.023), calcifications ( P = 0.036), architectural distortion ( P = 0.001), and lymphovascular invasion ( P = 0.049) were associated with axillary LN metastasis. At multivariate analysis, shorter skin-to-tumor distance (odds ratio [OR] = 4.15; 95% confidence interval [CI] = 1.01-16.19; P = 0.040) and masses with associated architectural distortion (OR = 3.80; 95% CI = 1.57-9.19; P = 0.003) were independent predictors of axillary LN metastasis. Conclusion US features of breast cancer can be promising factors associated with axillary LN metastasis in patients with clinically node-negative early-stage breast cancer.

  20. History of Non-Muscle-Invasive Bladder Cancer May Have a Worse Prognostic Impact in cT2-4aN0M0 Bladder Cancer Patients Treated With Radical Cystectomy.

    PubMed

    Kayama, Emina; Kikuchi, Eiji; Fukumoto, Keishiro; Shirotake, Suguru; Miyazaki, Yasumasa; Hakozaki, Kyohei; Kaneko, Gou; Yoshimine, Shunsuke; Tanaka, Nobuyuki; Takahiro, Maeda; Kanai, Kunimitsu; Oyama, Masafumi; Nakajima, Yosuke; Hara, Satoshi; Monma, Tetsuo; Oya, Mototsugu

    2018-04-28

    To investigate whether a history of non-muscle-invasive bladder cancer (NMIBC) plays a prognostic role in patients with muscle-invasive bladder cancer (MIBC) treated with radical cystectomy in the era when neoadjuvant chemotherapy was established as standard therapy for MIBC. A total of 282 patients who were diagnosed with cT2-T4aN0M0 bladder cancer treated with open radical cystectomy at our institutions were included. Initially diagnosed MIBC without a history of NMIBC was defined as primary MIBC group (n = 231), and MIBC that progressed from NMIBC was defined as progressive MIBC (n = 51). The rate of cT3/4a tumors was significantly higher in the primary MIBC group than in the progressive MIBC group (P = .004). Five-year recurrence-free survival and cancer-specific survival (CSS) rates for the primary MIBC group versus progressive MIBC group were 68.2% versus 55.9% (P = .039) and 76.1% versus 61.6% (P = .005), respectively. Progressive MIBC (hazard ratio, 2.170; P = .008) was independently associated with cancer death. In the primary MIBC group, the 5-year CSS rate in patients treated with neoadjuvant chemotherapy was 85.4%, which was significantly higher than that in patients without (71.5%, P = .023). In the progressive MIBC group, no significant differences were observed in CSS between patients treated with and without neoadjuvant chemotherapy. MIBC that progressed from NMIBC had a significantly worse clinical outcome than MIBC without a history of NMIBC and may not respond as well to neoadjuvant chemotherapy. These results are informative, even for NMIBC patients treated with conservative intravesical therapy. Copyright © 2018 Elsevier Inc. All rights reserved.

  1. Expression and mutational analysis of Cip/Kip family in early glottic cancer.

    PubMed

    Kim, D-K; Lee, J H; Lee, O J; Park, C H

    2015-02-01

    Genetic alteration of cyclin-dependent kinase inhibitors has been associated with carcinogenesis mechanisms in various organs. This study aimed to evaluate the expression and mutational analysis of Cip/Kip family cyclin-dependent kinase inhibitors (p21CIP1/WAF1, p27KIP1 and p57KIP2) in early glottic cancer. Expressions of Cip/Kip family and p53 were determined by quantitative reverse transcription polymerase chain reaction and densitometry. For the analysis of p21 inactivation, sequence alteration was assessed using single-strand conformational polymorphism polymerase chain reaction. Additionally, the inactivation mechanism of p27 and p57 were investigated using DNA methylation analysis. Reduced expression of p27 and p57 were detected in all samples, whereas the expression of p21 was incompletely down-regulated in 6 of 11 samples. Additionally, single-strand conformational polymorphism polymerase chain reaction analysis showed the p53 mutation at exon 6. Methylation of p27 and p57 was detected by DNA methylation assay. Our results suggest that the Cip/Kip family may have a role as a molecular mechanism of carcinogenesis in early glottic cancer.

  2. Bipedicled strap muscle transposition for vocal fold deficit after laser cordectomy in early glottic cancer patients.

    PubMed

    Su, Chih-Ying; Chuang, Hui-Ching; Tsai, Shang-Shyue; Chiu, Jeng-Fen

    2005-03-01

    In treating early glottic carcinomas, the outcomes of endoscopic laser cordectomy have been proven to be valuable in local control, survival, and vocal function preservation. In some extended cases, however, laser cordectomy may leave patients with poor vocal function because of vocal fold deficit. This work assesses the vocal outcome of medialization laryngoplasty with bipedicled strap muscle transposition for vocal fold deficit resulting from laser cordectomy in early glottic cancer patients. A prospective clinical series. Thirteen early glottic cancer patients who had vocal fold deficit caused by previous laser cordectomy underwent medialization laryngoplasty with bipedicled strap muscle transposition. The thyroid lamina on the cordectomy side was paramedially separated. The inner perichondrium was circumspectly raised from the overlying thyroid cartilage. After separating the thyrohyoid and cricothyroid membranes, the lamina was retracted laterally. A bipedicled strap muscle flap was then transposed into the area between the lamina and the paraglottic soft tissue. The thyroid cartilages were carefully sutured back in position. All patients received pre- and postoperative voice assessments comprising laryngostroboscopy and vocal function studies. Vocal enhancement was present in 92% (12/13) of patients after medialization laryngoplasty with strap muscle transposition. The glottal closure and maximal phonation time were noticeably improved by surgery. No dyspnea or other significant complications were observed in any patients. The outcomes show that bipedicled strap muscle transposition is a prosthesis-free, safe, and valuable laryngoplastic technique for correcting glottal incompetence caused by endoscopic laser cordectomy in early glottic cancer patients.

  3. Relevant reduction effect with a modified thermoplastic mask of rotational error for glottic cancer in IMRT

    NASA Astrophysics Data System (ADS)

    Jung, Jae Hong; Jung, Joo-Young; Cho, Kwang Hwan; Ryu, Mi Ryeong; Bae, Sun Hyun; Moon, Seong Kwon; Kim, Yong Ho; Choe, Bo-Young; Suh, Tae Suk

    2017-02-01

    The purpose of this study was to analyze the glottis rotational error (GRE) by using a thermoplastic mask for patients with the glottic cancer undergoing intensity-modulated radiation therapy (IMRT). We selected 20 patients with glottic cancer who had received IMRT by using the tomotherapy. The image modalities with both kilovoltage computed tomography (planning kVCT) and megavoltage CT (daily MVCT) images were used for evaluating the error. Six anatomical landmarks in the image were defined to evaluate a correlation between the absolute GRE (°) and the length of contact with the underlying skin of the patient by the mask (mask, mm). We also statistically analyzed the results by using the Pearson's correlation coefficient and a linear regression analysis ( P <0.05). The mask and the absolute GRE were verified to have a statistical correlation ( P < 0.01). We found a statistical significance for each parameter in the linear regression analysis (mask versus absolute roll: P = 0.004 [ P < 0.05]; mask versus 3D-error: P = 0.000 [ P < 0.05]). The range of the 3D-errors with contact by the mask was from 1.2% - 39.7% between the maximumand no-contact case in this study. A thermoplastic mask with a tight, increased contact area may possibly contribute to the uncertainty of the reproducibility as a variation of the absolute GRE. Thus, we suggest that a modified mask, such as one that covers only the glottis area, can significantly reduce the patients' setup errors during the treatment.

  4. Re-evaluation of Ipsilateral Radiation for T1-T2N0-N2b Tonsil Carcinoma at the Princess Margaret Hospital in the Human Papillomavirus Era, 25 Years Later

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Huang, Shao Hui, E-mail: shaohui.huang@rmp.uhn.on.ca; Waldron, John; Department of Otolaryngology—Head & Neck Surgery, The Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario

    Purpose: To report the outcome of ipsilateral radiation therapy (RT) in human papillomavirus (HPV)-positive (HPV+) patients and HPV-negative (HPV−) patients with T1-T2N0-N2b tonsillar cancer treated 25 years after our initial historical cohort. Methods and Materials: Patients with T1-T2N0-N2b tonsillar cancer who received ipsilateral RT or bilateral RT between 1999 and 2014 were reviewed. Overall survival (OS), local control (LC), regional control (RC), and grade 3 to 4 late toxicity (LT) were compared between ipsilateral RT and bilateral RT within HPV+ and HPV− patients, separately. Results: HPV status was ascertained in 379/427 (88%) consecutive patients (ipsilateral RT: 62 HPV+, 34 HPV−; bilateralmore » RT: 240 HPV+ 240, 41 HPV−). The proportion of ipsilateral RT by N category for HPV+ and HPV− patients were as follows: N0: 24/37 (65%) versus 28/48 (74%); N1: 21/49 (43%) versus 4/9 (44%); N2a: 10/39 (26%) versus 1/4 (25%); and N2b: 7/177 (4%) versus 1/24 (4%), respectively. Of the patients receiving ipsilateral RT, 94/96 (98%) were treated with RT alone. The median follow-up time was 5.03 years. The respective 5-year rates of OS, LC, RC, and LT were similar between ipsilateral RT and bilateral RT for the HPV+ patients (OS: 89% vs 87%, P=.55; LC: 97% vs 98%, P=.65; RC: 98% vs 97%, P=.27; LT: 17% vs 12%, P=.83) and HPV− patients (OS: 63% vs 48%, P=.27; LC: 90% vs 80%, P=.19; RC: 94% vs 83%, P=.14; LT: 15% vs 22%, P=.36). Of the 96 patients receiving ipsilateral RT, contralateral neck failure (CNF) occurred in 1/52 HPV+ patients and 1/34 HPV− patients. The 5-year CNF rates were 2% (95% CI: 1-9) (HPV+: 2% [0-14]; HPV−: 3% [0-21], P=.66). Five local failures (2 HPV+; 3 HPV−) and no distant failures were seen. The 5-year rates of LC, RC, and LT were 97% versus 90% (P=.24), 98% versus 94% (P=.25), and 18% versus 15% (P=.75) for the HPV+ and HPV− cohorts, respectively. Osteoradionecrosis occurred in 9 patients: 6/47 (13%) treated with

  5. A predictive model for recurrence in patients with glottic cancer implemented in a mobile application for Android.

    PubMed

    Jover-Esplá, Ana Gabriela; Palazón-Bru, Antonio; Folgado-de la Rosa, David Manuel; Severá-Ferrándiz, Guillermo; Sancho-Mestre, Manuela; de Juan-Herrero, Joaquín; Gil-Guillén, Vicente Francisco

    2018-05-01

    The existing predictive models of laryngeal cancer recurrence present limitations for clinical practice. Therefore, we constructed, internally validated and implemented in a mobile application (Android) a new model based on a points system taking into account the internationally recommended statistical methodology. This longitudinal prospective study included 189 patients with glottic cancer in 2004-2016 in a Spanish region. The main variable was time-to-recurrence, and its potential predictors were: age, gender, TNM classification, stage, smoking, alcohol consumption, and histology. A points system was developed to predict five-year risk of recurrence based on a Cox model. This was validated internally by bootstrapping, determining discrimination (C-statistics) and calibration (smooth curves). A total of 77 patients presented recurrence (40.7%) in a mean follow-up period of 3.4 ± 3.0 years. The factors in the model were: age, lymph node stage, alcohol consumption and stage. Discrimination and calibration were satisfactory. A points system was developed to obtain the probability of recurrence of laryngeal glottic cancer in five years, using five clinical variables. Our system should be validated externally in other geographical areas. Copyright © 2018 Elsevier Ltd. All rights reserved.

  6. Estrogen/Progesterone Receptor Negativity and HER2 Positivity Predict Locoregional Recurrence in Patients With T1a,bN0 Breast Cancer

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Albert, Jeffrey M.; Gonzalez-Angulo, Ana M.; Guray, Merih

    2010-08-01

    Purpose: Data have suggested that the molecular features of breast cancer are important determinants of outcome; however, few studies have correlated these features with locoregional recurrence (LRR). In the present study, we evaluated estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) as predictors of LRR in patients with lymph node-negative disease and tumors {<=}1 cm, because these patients often do not receive adjuvant chemotherapy or trastuzumab. Methods and Materials: The data from 911 patients with stage T1a,bN0 breast cancer who had received definitive treatment at our institution between 1997 and 2002 were retrospectively reviewed.more » We prospectively analyzed ER/PR/HER2 expression from the archival tissue blocks of 756 patients. These 756 patients represented the cohort for the present study. Results: With a median follow-up of 6.0 years, the 5- and 8-year Kaplan-Meier LRR rate was 1.6% and 5.9%, respectively, with no difference noted in those who underwent breast conservation therapy vs. mastectomy (p = .347). The 8-year LRR rates were greater in the patients with ER-negative (10.6% vs. 4.2%, p = .016), PR-negative (9.0% vs. 4.2%, p = .009), or HER2-positive (17.5% vs. 3.9%, p = 0.009) tumors. On multivariate analysis, ER-negative and PR-negative disease (hazard ratio, 2.37; p = .046) and HER2-positive disease (hazard ratio, 3.13, p = .016) independently predicted for LRR. Conclusion: Patients with ER/PR-negative or HER2-positive T1a,bN0 breast cancer had a greater risk of LRR. Therapeutic strategies, such as the use of chemotherapy and/or anti-HER2 therapies, should be considered for future clinical trials for these patients.« less

  7. Does neoadjuvant/perioperative chemotherapy improve overall survival for T2N0 gastric adenocarcinoma?

    PubMed

    Gabriel, Emmanuel; Attwood, Kristopher; Narayanan, Sumana; Brady, Maureen; Nurkin, Steven; Hochwald, Steven; Kukar, Moshim

    2018-03-01

    The purpose of this study was to determine whether neoadjuvant and/or perioperative chemotherapy (NAC) has an overall survival (OS) benefit for patients with T2N0 gastric adenocarcinoma. We performed retrospective analyses using the National Cancer Data Base, 2004-2013. Patients with T2N0 gastric adenocarcinoma were divided into two treatment groups: (1) NAC plus surgery (NA + S) and (2) surgery alone (S). Of 1,704 patients included, 277 (16.3%) received NAC, and 1,427 (83.7%) were treated with surgery alone. Patients in the NA + S group were more likely to be younger, have fewer comorbidities, and have larger tumors located in the proximal stomach. Although in an unadjusted analysis of OS, the NA + S group had improved survival compared to the S group (HR = 0.81, 95% CI 0.67-0.99, P < 0.0001), this was not maintained in a propensity adjusted analysis (HR = 0.89, 95% CI 0.68-1.18, P = 0.42). Similarly, propensity adjusted analyses accounting for potential bias from clinical misstaging or treatment effect from NAC did not show any OS benefit from NAC. Based on the largest cohort of clinically staged T2N0 gastric adenocarcinoma, there was no OS benefit derived from NAC compared to surgery alone. For select patients with reliable preoperative staging, NAC may be omitted. © 2017 Wiley Periodicals, Inc.

  8. Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with T2 to T4, N0 and N1 breast cancer.

    PubMed

    Andreis, D; Bonardi, S; Allevi, G; Aguggini, S; Gussago, F; Milani, M; Strina, C; Spada, D; Ferrero, G; Ungari, M; Rocca, A; Nanni, O; Roviello, G; Berruti, A; Harris, A L; Fox, S B; Roviello, F; Polom, K; Bottini, A; Generali, D

    2016-10-01

    Histological status of axillary lymph nodes is an important prognostic factor in patients receiving surgery for breast cancer (BC). Sentinel lymph node (SLN) biopsy (B) has rapidly replaced axillary lymph node dissection (ALND), and is now the standard of care for axillary staging in patients with clinically node-negative (N0) operable BC. The aim of this study is to compare pretreatment lymphoscintigraphy with a post primary systemic treatment (PST) scan in order to reduce the false-negative rates for SLNB. In this single-institution study we considered 170 consecutive T2-4 N0-1 M0 BC patients treated with anthracycline-based PST. At the time of incisional biopsy, we performed sentinel lymphatic mapping. After PST, all patients repeated lymphoscintigraphy with the same methodology. During definitive surgery we performed further sentinel lymphatic mapping, SLNB and ALND. The SLN was removed in 158/170 patients giving an identification rate of 92.9% (95% confidence interval (CI) = 88.0-96.3%) and a false-negative rate of 14.0% (95% CI = 6.3-25.8%). SLNB revealed a sensitivity of 86.0% (95% CI = 74.2-93.7%), an accuracy of 94.9% (95% CI = 90.3-97.8%) and a negative predictive value of 92.7% (95% CI = 86.1-96.8%). Identification rate, sensitivity and accuracy are in accordance with other studies on SLNB after PST, even after clinically negative node conversion following PST. This study confirms that diagnostic biopsy and neoadjuvant chemotherapy maintain breast lymphatic drainage unaltered. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Postoperative radiation therapy of pT2-3N0M0 esophageal carcinoma-a review.

    PubMed

    Luo, Yijun; Wang, Xiaoli; Yu, Jinming; Zhang, Bin; Li, Minghuan

    2016-11-01

    Esophageal cancer is one of the most malignant gastrointestinal cancers worldwide. Despite advances in surgical technique, 5-year survival in pathologic stage T2-3N0M0 esophageal squamous cell carcinoma patients who are treated with surgery alone is still poor. The addition of adjuvant radiotherapy may confer a benefit for these patients. However, not all patients could get a benefit from radiotherapy and patients with esophageal squamous cell carcinoma receiving radiotherapy seem to have a disparity in treatment response. Thus, identifying effective prognostic indicator to complement current clinical staging approaches is extremely important. Those prognostic factors could give rise to a novel prognostic stratification system, which serve as criteria for selecting patients for adjuvant therapy. Consequently, it may help to define the subgroups who are more likely to benefit from postoperative radiation therapy.

  10. Outcomes of Surgical Resection of T1bN0 Esophageal Cancer and Assessment of Endoscopic Mucosal Resection for Identifying Low-Risk Cancers Appropriate for Endoscopic Therapy.

    PubMed

    Mohiuddin, Kamran; Dorer, Russell; El Lakis, Mustapha A; Hahn, Hejin; Speicher, James; Hubka, Michal; Low, Donald E

    2016-08-01

    Invasive esophageal cancers have been managed historically with esophagectomy. Low-risk T1b patients are being proposed for nonsurgical management. The purpose of this study was to evaluate the ability of endoscopic mucosal resections (EMR) to identify low-risk T1b patients and to review surgical treatment outcomes for T1b cancer. All esophageal cancer patients, in an institutional review board-approved prospective database, between 2000 and 2013 with clinical stage (cT1bN0), pathological stage (pT1bN0), and no neoadjuvant therapy were retrospectively reviewed. Fifty-one patients, 38 pT1b and 13 cT1b, were assessed. All cT1b had preoperative EMR and five were found to be understaged at esophagectomy. pT1bN0 patients had a mean age of 66 years, mean BMI of 30, and 95 % had adenocarcinoma. Thirty-eight pT1bN0 patients underwent esophagectomy with a median hospital length of stay (LOS) of 9 days. Complications occurred in 14 patients, but 71 % were minor (Accordion score 1-2). In-hospital 30- and 90-day mortality was zero. EMR specimens were re-reviewed to assess low-risk criteria. Degree of differentiation and the presence of lymphovascular invasion could be assessed in all EMR specimens; however, assessment of submucosal invasion limited to the superficial submucosal layer could not be determined in the majority of cases. Kaplan-Meier 5-year overall survival in pT1bN0 patients was 78.7 %. Clinical staging of superficial esophageal cancer can be inaccurate especially in submucosal tumors. EMR should be routinely used for preoperative staging. Healthy patients with clinical tumor stage greater than cT1a should undergo multidisciplinary review and be considered for surgical resection.

  11. Clinical outcomes using carbon-ion radiotherapy and dose-volume histogram comparison between carbon-ion radiotherapy and photon therapy for T2b-4N0M0 non-small cell lung cancer-A pilot study.

    PubMed

    Shirai, Katsuyuki; Kawashima, Motohiro; Saitoh, Jun-Ichi; Abe, Takanori; Fukata, Kyohei; Shigeta, Yuka; Irie, Daisuke; Shiba, Shintaro; Okano, Naoko; Ohno, Tatsuya; Nakano, Takashi

    2017-01-01

    The safety and efficacy of carbon-ion radiotherapy for advanced non-small cell lung cancer have not been established. We evaluated the clinical outcomes and dose-volume histogram parameters of carbon-ion radiotherapy compared with photon therapy in T2b-4N0M0 non-small cell lung cancer. Twenty-three patients were treated with carbon-ion radiotherapy between May 2011 and December 2015. Seven, 14, and 2 patients had T2b, T3, and T4, respectively. The median age was 78 (range, 53-91) years, with 22 male patients. There were 12 adenocarcinomas, 8 squamous cell carcinomas, 1 non-small cell lung carcinoma, and 2 clinically diagnosed lung cancers. Eleven patients were operable, and 12 patients were inoperable. Most patients (91%) were treated with carbon-ion radiotherapy of 60.0 Gy relative biological effectiveness (RBE) in 4 fractions or 64.0 Gy (RBE) in 16 fractions. Local control and overall survival rates were calculated. Dose-volume histogram parameters of normal lung and tumor coverages were compared between carbon-ion radiotherapy and photon therapies, including three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT). The median follow-up of surviving patients was 25 months. Three patients experienced local recurrence, and the 2-year local control rate was 81%. During follow-up, 5 patients died of lung cancer, and 1 died of intercurrent disease. The 2-year overall survival rate was 70%. Operable patients had a better overall survival rate compared with inoperable patients (100% vs. 43%; P = 0.04). There was no grade ≥2 radiation pneumonitis. In dose-volume histogram analysis, carbon-ion radiotherapy had a significantly lower dose to normal lung and greater tumor coverage compared with photon therapies. Carbon-ion radiotherapy was effectively and safely performed for T2b-4N0M0 non-small cell lung cancer, and the dose distribution was superior compared with those for photon therapies. A Japanese multi-institutional study is

  12. Prognostic stratification of patients with T3N1M0 non-small cell lung cancer: which phase should it be?

    PubMed

    Kilicgun, Ali; Tanriverdi, Ozgur; Turna, Akif; Metin, Muzaffer; Sayar, Adnan; Solak, Okan; Urer, Nur; Gurses, Atilla

    2012-06-01

    In the 1997 revision of the TNM staging system for lung cancer, patients with T3N0M0 disease were moved from stage IIIA to stage IIB since these patients have a better prognosis. Despite this modification, the local lymph node metastasis remained the most important prognostic factor in patients with lung cancer. The present study aimed to evaluate the prognosis of patients with T3N1 disease as compared with that of patients with stages IIIA and IIB disease. During 7-year period, 313 patients with non-small cell lung cancer (297 men, 16 women) who had resection were enrolled. The patients were staged according the 2007 revision of Lung Cancer Staging by American Joint Committee on Cancer. The Kaplan-Meier statistics was used for survival analysis, and comparisons were made using Cox proportional hazard method. The 5-year survival of patients with stage IIIA disease excluding T3N1 patients was 40%, whereas the survival of the patients with stage IIB disease was 66% at 5 years. The 5-year survival rates of stage III T3N1 patients (single-station N1) was found to be higher than those of patients with stage IIIA disease (excluding pT3N1 patients, P = 0.04), while those were found to be similar with those of patients with stage IIB disease (P = 0.4). Survival of the present cohort of patients with T3N1M0 disease represented the survival of IIB disease rather than IIIA non-small cell lung cancer. Further studies are needed to suggest further revisions in the recent staging system regarding T3N1MO disease.

  13. Comparison of survival between radiation therapy and trans-oral laser microsurgery for early glottic cancer patients; a retrospective cohort study.

    PubMed

    De Santis, R J; Poon, I; Lee, J; Karam, I; Enepekides, D J; Higgins, K M

    2016-08-02

    The literature reports various treatment methodologies, such as trans-oral laser microsurgery, radiation therapy, total/partial laryngectomies, and concurrent radiation chemotherapy for patients with early larynx cancer. However, at the forefront of early glottis treatment is trans-oral laser microsurgery and radiation therapy, likely due to better functional and survival outcomes. Here we conduct the largest Canadian head-to-head comparison of consecutive patients treated with either radiation therapy or trans-oral laser microsurgery. Additionally, we compare these two treatments and their 5-year survival rates post treatment to add to the existing literature. Charts of patients who were diagnosed with early glottic cancer between 2006 and 2013 were reviewed. Seventy-five patients were identified, and split into 2 groups based on their primary treatment, trans-oral laser microsurgery and radiation therapy. Kaplan-Meier survival curves, life-tables, and the log-rank statistic were reported to determine if there was a difference between the two treatment groups and their disease-specific survival, disease-free survival, and total laryngectomy-free survival. Additionally, each different survival analysis was stratified by potential confounding variables, to help conclude which treatment is more efficacious in this population. The 5-year disease-specific survival rate is 93.3 % σ = 0.063 and 90.8 % σ = 0.056 for patients treated with trans-oral laser microsurgery and radiation therapy, respectively (χ (2) < 0.001, p = 0.983). The disease free survival rate is 60.0 % (σ =0.121) for patients treated with trans-oral laser microsurgery, and 67.2 % (σ = 0.074) for those who received RT (χ (2) = 0.19, p = 0.663). Additionally, the total laryngectomy-free survival rate is 84.1 % (σ = 0.1) and 79.1 % (σ = 0.072) for patients' early glottic cancer treated by trans-oral laser microsurgery and radiation therapy, respectively (

  14. Impact of concomitant chemoradiation on survival for patients with T1-2N1 head and neck cancer.

    PubMed

    Zumsteg, Zachary S; Kim, Sungjin; David, John M; Yoshida, Emi J; Tighiouart, Mourad; Shiao, Stephen L; Scher, Kevin; Mita, Alain; Sherman, Eric J; Lee, Nancy Y; Ho, Allen S

    2017-05-01

    Single-modality radiotherapy is considered a standard-of-care option for certain stage III, T1-2N1 head and neck squamous cell carcinomas (HNSCCs). The role of concomitant chemoradiation is not well established because there have been no studies comparing chemoradiation with radiation alone in this population. This study analyzed patients in the National Cancer Data Base with cT1-2N1M0 invasive squamous cell carcinomas of the oropharynx, larynx, and hypopharynx who were diagnosed between 2004 and 2012 and were undergoing definitive radiation. Patients who were undergoing surgery before radiation with unknown follow-up or for whom either the receipt or timing of chemotherapy was unknown were excluded. In all, 5030 patients with T1-2N1 oropharyngeal, laryngeal, or hypopharyngeal cancer were included. The median follow-up was 56.8 months (95% confidence interval [CI], 55.7-58.6 months). Overall, 68% of the patients received concomitant chemoradiation (CCRT). The use of CCRT significantly increased during the time period of this study from 53% in 2004 to 78% in 2012 (P < .001). CCRT was associated with improved overall survival (OS) in comparison with radiation alone in a multivariate analysis (hazard ratio [HR], 0.80; 95% CI, 0.72-0.88; P < .001). In propensity score-adjusted analyses, CCRT remained significantly associated with improved OS, with 5-year OS rates of 63.5% (95% CI, 60.7%-66.2%) and 55.6% (95% CI, 52.7%-58.4%; P < .001) with CCRT and radiation alone, respectively. Subgroup analyses showed a benefit across the majority of subgroups, including patients with oropharyngeal cancer (HR, 0.74; 95% CI, 0.65-0.85; P < .001). Concomitant chemoradiation is associated with improved survival for patients with T1-2N1 HNSCC. Prospective trials in this population should be pursued. Cancer 2017;123:1555-1565. © 2017 American Cancer Society. © 2016 American Cancer Society.

  15. Breast-conserving therapy versus mastectomy in T1-2N2 stage breast cancer: a population-based study on 10-year overall, relative, and distant metastasis-free survival in 3071 patients.

    PubMed

    van Maaren, M C; de Munck, L; Jobsen, J J; Poortmans, P; de Bock, G H; Siesling, S; Strobbe, L J A

    2016-12-01

    Our previous study demonstrated breast-conserving surgery with radiation therapy (BCT) to be at least equivalent to mastectomy in T1-2N0-1 breast cancer. Yet, 10-year survival rates after BCT and mastectomy with radiation therapy (MAST) in T1-2N2 breast cancer specifically have not been examined. Our study aimed to determine 10-year overall (OS), relative (RS), and distant metastasis-free survival (DMFS) in T1-2N2 breast cancer after BCT and MAST, stratified for T category. All women diagnosed with primary invasive T1-2N2 breast cancer in 2000-2004, treated with BCT or MAST, both with axillary dissection and RT, were selected from the Netherlands Cancer Registry. Ten-year OS and DMFS were estimated using multivariable Cox regression. Excess mortality ratios (EMR) were calculated to estimate RS, using life tables of the general population. OS and RS were determined on the whole cohort, and DMFS on the 2003 cohort with completed follow-up. Missing data were imputed. Of 3071 patients, 1055 (34.4 %) received BCT and 2016 (65.7 %) MAST. BCT and MAST showed equal 10-year OS and RS. After stratification, BCT was significantly associated with improved 10-year OS [HR adjusted 0.82 (95 % CI 0.71-0.96)] and RS (EMR adjusted 0.81 (95 % CI 0.67-0.97]) in T2N2, but not in T1N2. Ten-year DMFS was equal for both treatments [HR adjusted 0.87 (95 % CI 0.64-1.18)] in the 2003 cohort (n = 594), which was representative for the full cohort. BCT showed at least equal 10-year OS, RS, and DMFS compared to MAST. These results confirm that BCT is a good treatment option in T1-2N2 breast cancer.

  16. Quality of life and voice assessment in patients with early-stage glottic cancer.

    PubMed

    Arias, Fernando; Arraras, Juan Ignacio; Asin, Gemma; Uzcanga, María Itziar; Maraví, Enrique; Chicata, Volker; Eito, Clara; Zarandona, Uxue; Mora, Itxaso; Vila, Meritxell; Domínguez, Miguel Angel

    2015-03-01

    The purpose of this study was to assess the quality of life (QOL) and voice handicap in a sample of disease-free patients who had been treated at our center with radiotherapy (RT) or surgery for early glottic cancer. QOL and voice handicap were assessed using the European Organisation for Research and Treatment of Cancer (EORTC) questionnaires Quality of Life Questionnaire-Core 30-questions (QLQ-C30) and Quality of Life Questionnaire-Head and Neck 35-questions (QLQ-H&N35) and the Voice Handicap Index (VHI). Ninety-one patients completed the questionnaires. Fifty-nine patients (65%) were treated with RT and 32 (35%) with surgery. QOL scores for the sample recorded, moderate limitations in 6 areas, and more than moderate limitations (>30 of 100) in 2 areas. Significant differences were found in emotional functioning (88.5 vs 76.6) and social contact (4.6 vs 12.1) on the EORTC questionnaires and on the VHI (6.1 vs 12.8), which favored the RT group. In this cross-sectional study, voice quality, emotional functioning, and social contact were better in the RT group. © 2014 Wiley Periodicals, Inc.

  17. Whole-lesion apparent diffusion coefficient histogram analysis: significance in T and N staging of gastric cancers.

    PubMed

    Liu, Song; Zhang, Yujuan; Chen, Ling; Guan, Wenxian; Guan, Yue; Ge, Yun; He, Jian; Zhou, Zhengyang

    2017-10-02

    Whole-lesion apparent diffusion coefficient (ADC) histogram analysis has been introduced and proved effective in assessment of multiple tumors. However, the application of whole-volume ADC histogram analysis in gastrointestinal tumors has just started and never been reported in T and N staging of gastric cancers. Eighty patients with pathologically confirmed gastric carcinomas underwent diffusion weighted (DW) magnetic resonance imaging before surgery prospectively. Whole-lesion ADC histogram analysis was performed by two radiologists independently. The differences of ADC histogram parameters among different T and N stages were compared with independent-samples Kruskal-Wallis test. Receiver operating characteristic (ROC) analysis was performed to evaluate the performance of ADC histogram parameters in differentiating particular T or N stages of gastric cancers. There were significant differences of all the ADC histogram parameters for gastric cancers at different T (except ADC min and ADC max ) and N (except ADC max ) stages. Most ADC histogram parameters differed significantly between T1 vs T3, T1 vs T4, T2 vs T4, N0 vs N1, N0 vs N3, and some parameters (ADC 5% , ADC 10% , ADC min ) differed significantly between N0 vs N2, N2 vs N3 (all P < 0.05). Most parameters except ADC max performed well in differentiating different T and N stages of gastric cancers. Especially for identifying patients with and without lymph node metastasis, the ADC 10% yielded the largest area under the ROC curve of 0.794 (95% confidence interval, 0.677-0.911). All the parameters except ADC max showed excellent inter-observer agreement with intra-class correlation coefficients higher than 0.800. Whole-volume ADC histogram parameters held great potential in differentiating different T and N stages of gastric cancers preoperatively.

  18. Limitations of PET/CT in the Detection of Occult N1 Metastasis in Clinical Stage I(T1-2aN0) Non-Small Cell Lung Cancer for Staging Prior to Stereotactic Body Radiotherapy.

    PubMed

    Akthar, Adil S; Ferguson, Mark K; Koshy, Matthew; Vigneswaran, Wickii T; Malik, Renuka

    2017-02-01

    Patients receiving stereotactic body radiotherapy for stage I non-small cell lung cancer are typically staged clinically with positron emission tomography-computed tomography. Currently, limited data exist for the detection of occult hilar/peribronchial (N1) disease. We hypothesize that positron emission tomography-computed tomography underestimates spread of cancer to N1 lymph nodes and that future stereotactic body radiotherapy patients may benefit from increased pathologic evaluation of N1 nodal stations in addition to N2 nodes. A retrospective study was performed of all patients with clinical stage I (T1-2aN0) non-small cell lung cancer (American Joint Committee on Cancer, 7th edition) by positron emission tomography-computed tomography at our institution from 2003 to 2011, with subsequent surgical resection and lymph node staging. Findings on positron emission tomography-computed tomography were compared to pathologic nodal involvement to determine the negative predictive value of positron emission tomography-computed tomography for the detection of N1 nodal disease. An analysis was conducted to identify predictors of occult spread. A total of 105 patients with clinical stage I non-small cell lung cancer were included in this study, of which 8 (7.6%) patients were found to have occult N1 metastasis on pathologic review yielding a negative predictive value for N1 disease of 92.4%. No patients had occult mediastinal nodes. The negative predictive value for positron emission tomography-computed tomography in patients with clinical stage T1 versus T2 tumors was 72 (96%) of 75 versus 25 (83%) of 30, respectively ( P = .03), and for peripheral versus central tumor location was 77 (98%) of 78 versus 20 (74%) of 27, respectively ( P = .0001). The negative predictive values for peripheral T1 and T2 tumors were 98% and 100%, respectively; while for central T1 and T2 tumors, the rates were 85% and 64%, respectively. Occult lymph node involvement was not associated with

  19. Limitations of PET/CT in the Detection of Occult N1 Metastasis in Clinical Stage I(T1-2aN0) Non-Small Cell Lung Cancer for Staging Prior to Stereotactic Body Radiotherapy

    PubMed Central

    Akthar, Adil S.; Ferguson, Mark K.; Koshy, Matthew; Vigneswaran, Wickii T.

    2016-01-01

    Purpose/Objectives: Patients receiving stereotactic body radiotherapy for stage I non-small cell lung cancer are typically staged clinically with positron emission tomography–computed tomography. Currently, limited data exist for the detection of occult hilar/peribronchial (N1) disease. We hypothesize that positron emission tomography–computed tomography underestimates spread of cancer to N1 lymph nodes and that future stereotactic body radiotherapy patients may benefit from increased pathologic evaluation of N1 nodal stations in addition to N2 nodes. Materials/Methods: A retrospective study was performed of all patients with clinical stage I (T1-2aN0) non-small cell lung cancer (American Joint Committee on Cancer, 7th edition) by positron emission tomography–computed tomography at our institution from 2003 to 2011, with subsequent surgical resection and lymph node staging. Findings on positron emission tomography–computed tomography were compared to pathologic nodal involvement to determine the negative predictive value of positron emission tomography–computed tomography for the detection of N1 nodal disease. An analysis was conducted to identify predictors of occult spread. Results: A total of 105 patients with clinical stage I non-small cell lung cancer were included in this study, of which 8 (7.6%) patients were found to have occult N1 metastasis on pathologic review yielding a negative predictive value for N1 disease of 92.4%. No patients had occult mediastinal nodes. The negative predictive value for positron emission tomography–computed tomography in patients with clinical stage T1 versus T2 tumors was 72 (96%) of 75 versus 25 (83%) of 30, respectively (P = .03), and for peripheral versus central tumor location was 77 (98%) of 78 versus 20 (74%) of 27, respectively (P = .0001). The negative predictive values for peripheral T1 and T2 tumors were 98% and 100%, respectively; while for central T1 and T2 tumors, the rates were 85% and 64

  20. National Practice Patterns for Clinical T1N0 Nasopharyngeal Cancer in the Elderly: A National Cancer Data Base Analysis.

    PubMed

    Post, Carl M; Lin, Chi; Adeberg, Sebastian; Gupta, Mrigank; Zhen, Weining; Verma, Vivek

    2018-03-01

    The standard of care for T1N0 nasopharyngeal cancer (NPC) is definitive radiation therapy (RT). However, practice patterns in the elderly may not necessarily follow national guidelines. Herein, we investigated national practice patterns for T1N0 NPC. The National Cancer Data Base (NCDB) was queried for clinical T1N0 primary NPC cases (2004-2013) in patients ≥70 years old. Patient, tumor, and treatment parameters were extracted. Kaplan-Meier analysis was used to compare overall survival (OS) between patients receiving RT versus those under observation. Logistic regression was used to examine variables associated with receipt of RT. Cox proportional hazards modeling determined variables associated with OS. Landmark analysis of patients surviving 1 year or more was performed to assess survival differences between groups. In total, data of 147 patients were analyzed. RT was delivered to 89 patients (61%), whereas 58 (39%) patients underwent observation. On multivariable analysis, older patients were less likely to receive RT (p=0.003), but there were no differences between groups in terms of Charlson-Deyo comorbidity index. Median and 5-year OS in patients receiving RT versus those under observation were 71 and 33 months, and 59% and 48% (p=0.011), respectively. For patients surviving 1 year or more (n=96), there was a strong trend showing that receipt of RT was associated with better median and 5-year OS. This National Data Base analysis shows that observation is relatively common for T1N0 NPC in the elderly, but is associated with poorer survival. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  1. [Evaluation of central lymph node dissection for papillary thyroid carcinoma in cN0 T1/T2].

    PubMed

    Zhao, S Y; Ma, Y H; Yin, Z; Zhan, X X; Cheng, R C; Qian, J

    2018-02-07

    Objective: To evaluate the application of the central lymph node dissection (CLND) for papillary thyroid carcinoma (PTC) in cN0 T1/T2. Methods: Retrospective analysis of 532 cases with PTC in cN0 T1/T2 who underwent CLND between October 2014 and September 2016 in the Department of Thyroid Surgery, the First Affiliated Hospital of the Kunming Medical University. The incidence of central lymph node (CLN) metastasis and risk factors were analyzed. Results: CLN metastasis rates: 41.2% (42/102) in males vs 34.9% (150/430) in females, P =0.252; 33.9% (116/342) in single focal carcinoma vs 40.4% (74/183) in multifocal carcinoma, P =0.157; 44.0% (125/284) in patients with 45 years old or less vs 27.0% (67/248) in patients more than 45 years old, P =0.000; 30.3% (113/373) in microcarcinoma vs 50.9% (81/159) in non-microcarcinoma, P =0.000.In unilateral lesions, ipsilateral CLN metastasis was correlated with the tumor diameter ( P =0.012), but not with the number of lesions ( P =0.653). also contralateral CLN metastasis was correlated with the tumor diameter ( P =0.000), but not with the number of lesions ( P =0.815). For the left or right unilateral single focal lesion, the tumor diameter was not correlated with the metastasis of the posterior to right recurrent laryngeal nerve central lymph nodes (LN-prRLN-CLN) ( P =0.652, P =0.088). But in bilateral multifocal carcinoma the tumor diameter was correlated with metastasis of LN-prRLN-CLN ( P =0.039). Conclusions: Prophylactic CLND is reasonable for PTC in cN0 T1/T2. A bilateral CLND should be conducted for patients with bilateral multi-focus cancer and unilateral or bilateral non-microcarcinoma, especially in patients more than 45 years old. For unilateral single focal microcarcinoma on the right, the content of CLND should be from laryngeal nerve on right center to posterior branche; for unilateral single focal microcarcinoma on the left side, the left CLND should be conducted. An ipsilateral CLND can be considered in

  2. Complete pathological response (ypT0N0M0) after preoperative chemotherapy alone for stage IV rectal cancer.

    PubMed

    Naiken, Surennaidoo P; Toso, Christian; Rubbia-Brandt, Laura; Thomopoulos, Theodoros; Roth, Arnaud; Mentha, Gilles; Morel, Philippe; Gervaz, Pascal

    2014-01-17

    Complete pathological response occurs in 10-20% of patients with rectal cancer who are treated with neoadjuvant chemoradiation therapy prior to pelvic surgery. The possibility that complete pathological response of rectal cancer can also occur with neoadjuvant chemotherapy alone (without radiation) is an intriguing hypothesis. A 66-year old man presented an adenocarcinoma of the rectum with nine liver metastases (T3N1M1). He was included in a reverse treatment, aiming at first downsizing the liver metastases by chemotherapy, and subsequently performing the liver surgery prior to the rectum resection. The neoadjuvant chemotherapy consisted in a combination of oxaliplatin, 5-FU, irinotecan, leucovorin and bevacizumab (OCFL-B). After a right portal embolization, an extended right liver lobectomy was performed. On the final histopathological analysis, all lesions were fibrotic, devoid of any viable cancer cells. One month after liver surgery, the rectoscopic examination showed a near-total response of the primary rectal adenocarcinoma, which convinced the colorectal surgeon to perform the low anterior resection without preoperative radiation therapy. Macroscopically, a fibrous scar was observed at the level of the previously documented tumour, and the histological examination of the surgical specimen did not reveal any malignant cells in the rectal wall as well as in the mesorectum. All 15 resected lymph nodes were free of tumour, and the final tumour stage was ypT0N0M0. Clinical outcome was excellent, and the patient is currently alive 5 years after the first surgery without evidence of recurrence. The presented patient with stage IV rectal cancer and liver metastases was in a unique situation linked to its inclusion in a reversed treatment and the use of neoadjuvant chemotherapy alone. The observed achievement of a complete pathological response after chemotherapy should promote the design of prospective randomized studies to evaluate the benefits of chemotherapy

  3. Comparison of the outcomes of stereotactic body radiotherapy and surgery in elderly patients with cT1-2N0M0 non-small cell lung cancer.

    PubMed

    Nakagawa, Tatsuo; Negoro, Yoshiharu; Matsuoka, Tomoaki; Okumura, Norihito; Dodo, Yoshihiro

    2014-07-01

    This study aimed to compare the outcomes of stereotactic body radiotherapy (SBRT) and surgery in elderly patients with cT1-2N0M0 non-small cell lung cancer (NSCLC). Elderly patients (≥75 years) with cT1-2 (≤5 cm) N0M0 NSCLC who were treated with SBRT (n=35) or surgery (n=183) between January 2001 and December 2011 were analyzed. The following radiation doses were administered: 48 Gy/4-6 fractions in 12 patients; 50 Gy/4-5 fractions in 20; and 60 Gy/8 fractions in 3. The following surgical methods were performed: pneumonectomy in 2 patients, lobectomy in 154, segmentectomy in 23, and wedge resection in 4. Patients in the SBRT group had a higher mean age, a worse performance status, and a lower percentage of forced expiratory volume in 1.0 s than those in the surgery group. The overall 5-year survival rates were 43.8% and 67.6% for the SBRT and surgery groups, respectively (p=0.057, log-rank test). Regarding tumor diameter, patients in the surgery group survived significantly longer than did those in the SBRT group (>20-mm tumors, p=0.027; >30-mm tumors p=0.043), whereas survival did not differ significantly between the groups for ≤20-mm tumors (p=0.982). Multivariate analysis confirmed the improved survival in the surgery group compared to the SBRT group for all tumors (p=0.034) and for >20-mm tumors (p=0.016). Post-therapeutic survival among elderly patients might be better with surgery than with SBRT in NSCLC patients with tumors >20 mm. Copyright © 2014 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

  4. Locoregional treatment and overall survival of men with T1a,b,cN0M0 breast cancer: A population-based study.

    PubMed

    Leone, José Pablo; Leone, Julieta; Zwenger, Ariel Osvaldo; Iturbe, Julián; Leone, Bernardo Amadeo; Vallejo, Carlos Teodoro

    2017-01-01

    Male breast cancer (MaBC) is an understudied disease; information about locoregional treatment and outcomes in patients with early stage is unknown. We aimed to analyse patient characteristics, locoregional treatment and overall survival (OS) of T1a,b,cN0M0 male breast cancer. We evaluated men with T1a,b,cN0M0 breast cancer reported to Surveillance, Epidemiology, and End Results program from 1988 to 2012. Univariate and multivariate analyses were performed to determine the effect of each variable on OS. We included 1263 patients. Median age was 66 years (range 27-103). Median follow-up was 62 months (range 1-294). OS at 5 and 10 years were 85.1% and 66.5%, respectively. Distribution according to tumour sub-stage was: T1a 6.5%, T1b 20.7% and T1c 72.8%. Mastectomy was performed in >74% of patients of each tumour size group and overall 44.1% had >5 lymph nodes examined (LNE). Univariate analysis showed that patients with T1c, no surgery and 0 LNE had worse prognosis. In multivariate analysis, older age (hazard ratio [HR] 11.09), grade 3/4 tumours (HR 1.7), no surgery (HR 3.3), 0 LNE (HR 5.1) and unmarried patients (HR 1.7) had significantly shorter OS. There were no differences in OS between breast conservation versus mastectomy and 1-5 LNE versus > 5 LNE. Men with early breast cancer have a favourable OS. However, older age, higher grade, no breast surgery, no LNE and unmarried status emerged as poor prognostic characteristics. Efforts to decrease the high rates of mastectomy and extensive LNE should be taken given similar OS observed with breast conservation and 1-5 LNE, respectively. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Efficacy of intermittent sub-glottic suctioning in prevention of ventilator-associated pneumonia- A preliminary study of 100 patients.

    PubMed

    Vijai, M N; Ravi, Parli R; Setlur, Rangaraj; Vardhan, Harsh

    2016-05-01

    Oropharyngeal colonisation followed by aspiration of contaminated secretions is the major cause for ventilator-associated pneumonia (VAP). Pooled secretions present in the sub-glottic area above inflated endotracheal tube cuff may be aspirated into the lower airways. It was hypothesised that intermittent suctioning of sub-glottic secretions would prevent VAP. Group I (n = 50) patients were intubated with HiLo Evac™ endotracheal (ET) tube with facility for sub-glottic suctioning, and Group II (n = 50) patients were intubated with HiLo Contour™ ET tube without such facility. In the Group I, sub-glottic suctioning was performed every 2 h. Incidence of VAP, mean ventilator days, Intensive Care Unit (ICU) stay and mortality were compared. Qualitative variables were reported as percentages and were compared by Chi-square test or unpaired two-tailed, Fisher's exact test, as appropriate, to analyse the significance of difference between the two groups. The two groups were similar with respect to demographic characteristics. VAP was seen in 6% of patients in Group I and 22% of patients in Group II (P = 0.021). Both early- and late-onset VAPs were significantly reduced in Group I. Both ventilator days (8.0 vs. 6.45; P = 0.001) and ICU stay (8.33 vs. 6.33; P = 0.001) on the day of onset of VAP were significantly more in the Group I. Total ventilator days were significantly less (6.52 vs. 8.32; P = 0.006) with lower incidence of mortality (36% vs. 48%; P = 0.224) in the Group I. Intermittent sub-glottic suctioning reduces the incidence of VAP including late-onset VAP.

  6. The role of intraoperative narrow-band imaging in transoral laser microsurgery for early and moderately advanced glottic cancer.

    PubMed

    Klimza, Hanna; Jackowska, Joanna; Piazza, Cesare; Banaszewski, Jacek; Wierzbicka, Malgorzata

    2018-03-01

    Trans-oral laser microsurgery is an established technique for the treatment of early and moderately advanced laryngeal cancer. The authors intend to test the usefulness of narrow-band imaging in the intraoperative assessment of the larynx mucosa in terms of specifying surgical margins. Forty-four consecutive T1-T2 glottic cancers treated with trans-oral laser microsurgery Type I-VI cordectomy were presented. Suspected areas (90 samples/44 patients) were biopsied under the guidance of narrow-band imaging and white light and sent for frozen section. Our study revealed that 75 of 90 (83.3%) white light and narrow-band imaging-guided samples were histopathologically positive: 30 (40%) were confirmed as carcinoma in situ or invasive carcinoma and 45 (60%) as moderate to severe dysplasia. In 6 patients mucosa was suspected only in narrow-band imaging, with no suspicion under white light. Thus, in these 6 patients 18/90 (20%) samples were taken. In 5/6 patients 16/18 (88.8%) samples were positive in frozen section: in 6/18 (33.3%) carcinoma (2 patients), 10/18 (66.6%) severe dysplasia was confirmed (3 patients). In 1 patient 2/18 (11.1%) samples were negative in frozen section. Presented analysis showed, that sensitivity, specificity and accuracy of white light was 79.5%, 20% and 71.1% respectively, while narrow-band imaging was 100%, 0.0% and 85.7%, respectively. The intraoperative use of narrow-band imaging proved to be valuable in the visualization of suspect areas of the mucosa. Narrow-band imaging confirms the suspicions undertaken in white light and importantly, it showed microlesions beyond the scope of white light. Copyright © 2018 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  7. Laryngeal cancer in the United States: changes in demographics, patterns of care, and survival.

    PubMed

    Hoffman, Henry T; Porter, Kimberly; Karnell, Lucy H; Cooper, Jay S; Weber, Randall S; Langer, Corey J; Ang, Kie-Kian; Gay, Greer; Stewart, Andrew; Robinson, Robert A

    2006-09-01

    Survival has decreased among patients with laryngeal cancer during the past 2 decades in the United States. During this same period, there has been an increase in the nonsurgical treatment of laryngeal cancer. The objectives of this study were to identify trends in the demographics, management, and outcome of laryngeal cancer in the United States and to analyze factors contributing to the decreased survival. The authors conducted a retrospective, longitudinal study of laryngeal cancer cases. Review of the National Cancer Data Base (NCDB) revealed 158,426 cases of laryngeal squamous cell carcinoma (excluding verrucous carcinoma) diagnosed between the years 1985 and 2001. Analysis of these case records addressed demographics, management, and survival for cases grouped according to stage, site, and specific TNM classifications. This review of data from the NCDB analysis confirms the previously identified trend toward decreasing survival among patients with laryngeal cancer from the mid-1980s to mid-1990s. Patterns of initial management across this same period indicated an increase in the use of chemoradiation with a decrease in the use of surgery despite an increase in the use of endoscopic resection. The most notable decline in the 5-year relative survival between the 1985 to 1990 period and the 1994 to 1996 period occurred among advanced-stage glottic cancer, early-stage supraglottic cancers, and supraglottic cancers classified as T3N0M0. Initial treatment of T3N0M0 laryngeal cancer (all sites) in the 1994 to 1996 period resulted in poor 5-year relative survival for those receiving either chemoradiation (59.2%) or irradiation alone (42.7%) when compared with that of patients after surgery with irradiation (65.2%) and surgery alone (63.3%). In contrast, identical 5-year relative survival (65.6%) rates were observed during this same period for the subset of T3N0M0 glottic cancers initially treated with either chemoradiation or surgery with irradiation. The decreased

  8. [Long term results of exclusive chemotherapy for glottic squamous cell carcinoma complete clinical responders after induction chemotherapy].

    PubMed

    Vachin, F; Hans, S; Atlan, D; Brasnu, D; Menard, M; Laccourreye, O

    2004-06-01

    To evaluate the long-term results of exclusive chemotherapy for T1-T3N0M0 glottic squamous cell carcinoma complete clinical responders after induction chemotherapy. Between 1985 and 2000, 69 patients with glottic squamous cell carcinoma complete clinical responders after induction chemotherapy were managed with exclusive chemotherapy at our department. Chemotherapy associated platinum and fluorouracil. This retrospective analysis evaluated actuarial survival, treatment morbidity, oncologic events and laryngeal preservation. Various independent factors were tested for potential correlation with survival and local recurrence. The 5-year Kaplan-Meier actuarial survival, local control, lymph node control estimate were 83,6%, 64,8%, 98,6% respectively. Chemotherapy never resulted in death. The 10-year actuarial metachronous second primary tumors estimate was 32%. The overall laryngeal preservation rate was 98,6%. Altogether our data and the review of the literature suggest that in patients achieving a complete clinical response after and induction based chemotherapy regimen, the completion of an exclusive chemotherapy regimen appears to be a valid alternative to the conventional use of radiotherapy or chemo-radiation protocols.

  9. Potential clinical value of PET/CT in predicting occult nodal metastasis in T1-T2N0M0 lung cancer patients staged by PET/CT

    PubMed Central

    Zhou, Xiang; Chen, Ruohua; Huang, Gang; Liu, Jianjun

    2017-01-01

    We assessed the clinical value of 2-fluoro-2-deoxyglucose (18F-FDG) PET/CT imaging for predicting occult nodal metastasis in non-small cell lung cancer (NSCLC) patients. This retrospective study included 54 patients with T1-2N0M0 NSCLC who had undergone 18F-FDG PET/CT before surgery. Occult nodal metastasis was detected in 25.9% (14/54) of the patients. Immunohistochemical analysis revealed that increased glucose transporter 1 expression was associated with occult nodal metastasis, but hexokinase 2 expression was not. Compared to the negative nodal metastasis group, the positive nodal metastasis group was associated with increased maximum standardized uptake value (SUVmax) and tumor size. Multivariate analysis indicated that SUVmax and tumor size were associated with nodal metastasis. Nodal metastasis could be predicted with a sensitivity of 92.9% and a specificity of 55.0% when the SUVmax cutoff was 4.35. When patients were divided into low-risk (tumor size ≤ 2.5 cm and SUVmax ≤ 4.35), moderate-risk (tumor size ≤ 2.5 cm and SUVmax > 4.35 or tumor size > 2.5 cm and SUVmax ≤ 4.35) and high-risk (tumor size > 2.5 cm and SUVmax > 4.35) groups, the lymph node metastasis rates were 4.3%, 22.7%, and 88.9%, respectively. These results indicate that the combination of SUVmax and tumor size has potential clinical value for predicting occult nodal metastasis in NSCLC patients. PMID:29137276

  10. Comparison of glottic visualisation and ease of intubation with different laryngoscope blades.

    PubMed

    Kulkarni, Atul P; Tirmanwar, Amar S

    2013-03-01

    Literature suggests glottic view is better with straight blades while tracheal intubation is easier with curved blades. To compare glottic view and ease of intubation with Macintosh, Miller, McCoy blades and the Trueview(®) laryngoscope. This prospective randomised study was undertaken in operation theatres of a 550 bedded tertiary referral cancer centre after approval from the Institutional Review Board. We compared the Macintosh, Miller, McCoy blades and the Trueview(®) laryngoscope for glottic visualisation and ease of tracheal intubation; in 120 patients undergoing elective cancer surgery; randomly divided into four groups. After induction of anaesthesia laryngoscopy was performed and trachea intubated. We recorded: Visualisation of glottis (Cormack Lehane grade), ease of intubation, number of attempts; need to change the blade and need for external laryngeal manipulation. Demographic data, Mallampati classification were compared using the Chi-square test. A P<0.05 was considered significant. Grade 1 view was obtained most often (87% patients) with Trueview(®) laryngoscope. Intubation was easier (Grade 1) with Trueview(®) and McCoy blades (93% each). Seven patients needed two attempts; one patient in Miller group needed three attempts. No patient in McCoy and Trueview(®) Groups required external laryngeal manipulation. We found that in patients with normal airway glottis was best visualised with Miller blade and Trueview(®) laryngoscope however, the trachea was more easily intubated with McCoy and Macintosh blades and Trueview(®) laryngoscope.

  11. Comparative analysis between clinical outcomes of primary radical resection and second completion radical resection for T2 gallbladder cancer: single-center experience.

    PubMed

    Cho, Seong Yeon; Park, Sang-Jae; Kim, Seong Hoon; Han, Sung-Sik; Kim, Young-Kyu; Lee, Kwang-Woong

    2010-07-01

    Gallbladder (GB) cancer may be discovered incidentally by histopathologic examination following simple cholecystectomy. Incidental GB cancer > or =T2 or > or =N1 needs a second radical resection. It is a matter of concern whether the prognosis may be worse in patients with T2GB cancer who undergo a second radical resection than in those who undergo primary radical resection. Between March 2001 and March 2009, 21 patients underwent a one-step operation (OSO group), and 17 patients underwent a two-step operation (TSO group) for T2GB cancer. We compared clinicopathologic factors and survival between patients in the OSO group (n = 9) and those in the TSO group (n = 9) with T2N0M0 GB cancer and between patients in the OSO group (n = 12) and those in the TSO group (n = 8) with T2N1M0 GB cancer. Except for patient age, clinicopathologic factors as well as disease-free survival were not significantly different between the OSO group and the TSO group in the aforementioned cancer stages. Patient age was significantly higher in the OSO group than in the TSO group. Second completion radical resection following initial simple cholecystectomy (TSO) provided a survival benefit similar to that of primary radical surgery (OSO) for patients with both T2N0M0 and T2N1M0 GB cancers in our study.

  12. Clinical implications of proliferation activity in T1 or T2 male gastric cancer patients.

    PubMed

    Kim, Young-Woo; Eom, Bang Wool; Kook, Myeong-Cherl; Kim, Han-Seong; Kim, Mi-Kyung; Hwang, Hai-Li; Chandra, Vishal; Poojan, Shiv; Song, Yura; Koh, Jae-Soo; Bae, Chang-Dae; Ro, Jungsil; Hong, Kyeong-Man

    2015-11-06

    Proliferation activity has already been established as a prognostic marker or as a marker for anticancer drug sensitivity. In gastric cancer, however, the prognostic significance of proliferation activity is still being debated. Several studies evaluating proliferation activity using Ki-67 have shown controversial results in terms of the relationship between proliferation activity and overall survival (OS) or drug sensitivity in gastric cancer patients. Because cytoskeleton-associated protein 2 (CKAP2) staining has recently been introduced as a marker of proliferation activity, we analyzed 437 gastric cancer tissues through CKAP2 immunohistochemistry, and we evaluated the chromatin CKAP2-positive cell count (CPCC) for proliferation activity. Although the CPCC did not show any significant correlation with OS in the male, female or total number of cases, it did show a significant correlation in the T1 or T2 male patient subgroup, according to log-rank tests (P=0.001) and univariate analysis (P=0.045). Additionally, multivariate analysis with the Cox proportional hazard regression model showed a significant correlation between the CPCC and OS (P=0.039) for the co-variables of age, gender, T stage, N stage, histology, tumor location, tumor size and adjuvant chemotherapy. In male gastric cancer cell lines, faster-growing cancer cells showed higher sensitivity to cisplatin than slow-growing cells. Thus our study indicates that CPCC-measured proliferation activity demonstrates a significantly worse prognosis in T1 or T2 male gastric cancer patients. The CPCC will help to more precisely classify gastric cancer patients and to select excellent candidates for adjuvant chemotherapy, which in turn will facilitate further clinical chemotherapeutic trials.

  13. Effect of resection depth of early glottic cancer on vocal outcome: An optimized finite element simulation

    PubMed Central

    Mau, Ted; Palaparthi, Anil; Riede, Tobias; Titze, Ingo R.

    2015-01-01

    Objectives/Hypothesis To test the hypothesis that subligamental cordectomy produces superior acoustic outcome than subepithelial cordectomy for early (T1-2) glottic cancer that requires complete removal of the superficial lamina propria but does not involve the vocal ligament. Study Design Computer simulation Methods A computational tool for vocal fold surgical planning and simulation (the National Center for Voice and Speech Phonosurgery Optimizer-Simulator) was used to evaluate the acoustic output of alternative vocal fold morphologies. Four morphologies were simulated: normal, subepithelial cordectomy, subligamental cordectomy, and transligamental cordectomy (partial ligament resection). The primary outcome measure was the range of fundamental frequency (F0) and sound pressure level (SPL). A more restricted F0-SPL range was considered less favorable because of reduced acoustic possibilities given the same range of driving subglottic pressure and identical vocal fold posturing. Results Subligamental cordectomy generated solutions covering an F0-SPL range 82% of normal for a rectangular vocal fold. In contrast, transligamental and subepithelial cordectomies produced significantly smaller F0-SPL ranges, 57% and 19% of normal, respectively. Conclusion This study illustrates the use of the Phonosurgery Optimizer-Simulator to test a specific hypothesis regarding the merits of two surgical alternatives. These simulation results provide theoretical support for vocal ligament excision with maximum muscle preservation when superficial lamina propria resection is necessary but the vocal ligament can be spared on oncological grounds. The resection of more tissue may paradoxically allow the eventual recovery of a better speaking voice, assuming glottal width is restored. Application of this conclusion to surgical practice will require confirmatory clinical data. PMID:26010240

  14. Transoral Laser Microsurgery in Early Glottic Lesions.

    PubMed

    Sjögren, E V

    2017-01-01

    To give an overview of the evolvement of transoral laser microsurgery (TLM) in the treatment of early glottic carcinoma and highlight the contribution of recent literature. The indications and limits of TLM have been well specified. Effects on swallowing have been well documented. Introduction of narrow-band imaging (NBI) and diffusion-weighted magnetic resonance has been shown of additional value for outcome. The first reports on transoral robotic surgery show that it may be of added value in the future. TLM for early glottic carcinoma (Tis-T2) has very good oncological outcomes with indications of higher larynx preservation in TLM than that in radiotherapy. The anterior commissure is a risk factor if involved in the cranio-caudal plane, and reduced vocal fold mobility is a risk factor when this is due to arytenoid involvement. The best voice results are achieved when the anterior commissure can be left intact along with part of the vocal fold muscle although even in larger resections, patient self-reported voice handicap is still limited.

  15. Surgical Treatment of Iatrogenic Ventral Glottic Stenosis Using a Mucosal Flap Technique

    PubMed Central

    Barnett, Timothy P.; O'Leary, John Mark; Dixon, Padraic M.

    2016-01-01

    Objective To describe a novel surgical technique for correcting postoperative ventral glottic stenosis (cicatrix or web formation) and the outcome in 2 Thoroughbred racehorses. Study Design Retrospective case report. Animals Thoroughbreds diagnosed with ventral glottic stenosis (n=2). Methods Horses presenting with iatrogenic ventral glottic stenosis and resultant exercise intolerance and abnormal exercise‐related noise were anesthetized and a midline sagittal skin incision was made over the ventral larynx and between the sternohyoideus muscles overlying the cricothyroid notch. The cricothyroid ligament, attached laryngeal cicatrix, and overlying mucosa were sagittally sectioned at the dorsal aspect of the cicatrix on the left side. The laryngeal mucosa, cicatrix, and underlying cricothyroid ligament immediately rostral and caudal to the cicatrix were sectioned in a medial (axial) direction as far as the right side of the cricothyroid notch. After resection of the majority of the attached cicatrix tissue, the residual mucosal flap (attached to the right side of the larynx) was reflected ventrally and sutured to the attachment of the cricothyroid ligament on the right side of the cricothyroid notch, creating an intact mucosal layer on the right side of the ventral larynx. Results Both horses had good intralaryngeal wound healing with minimal redevelopment of ventral glottic stenosis at 5 and 9 months postoperatively and were successfully returned to racing with complete absence of abnormal respiratory noise. Conclusion The unique laryngeal anatomy of horses, with a cartilage‐free ventral laryngeal area (cricothyroid notch), allowed the use of this novel surgical technique to successfully treat ventral glottic stenosis. PMID:27013024

  16. Successful Completion of the Pilot Phase of a Randomized Controlled Trial Comparing Sentinel Lymph Node Biopsy to No Further Axillary Staging in Patients with Clinical T1-T2 N0 Breast Cancer and Normal Axillary Ultrasound

    PubMed Central

    Cyr, Amy E; Tucker, Natalia; Ademuyiwa, Foluso; Margenthaler, Julie A; Aft, Rebecca L; Eberlein, Timothy J; Appleton, Catherine M; Zoberi, Imran; Thomas, Maria A; Gao, Feng; Gillanders, William E

    2016-01-01

    Background Axillary surgery is not considered therapeutic in patients with clinical T1-T2 N0 breast cancer. The importance of axillary staging is eroding in an era where tumor biology, as defined by biomarker and gene expression profile, is increasingly important in medical decision making. We hypothesize that axillary ultrasound (AUS) is a noninvasive alternative to sentinel lymph node biopsy (SLNB), and AUS could replace SLNB without compromising patient care. Study Design Patients with clinical T1-T2 N0 breast cancer and normal AUS were eligible for enrollment. Subjects were randomized to no further axillary staging (Arm 1) versus SLNB (Arm 2). Descriptive statistics were used to describe the results of the pilot phase of the randomized controlled trial. Results 68 subjects were enrolled in the pilot phase of the trial (34 subjects in Arm 1, no further staging; 32 subjects in Arm 2, SLNB, and 2 subjects voluntarily withdrew from the trial). The median age was 61 years (range 40-80) in Arm 1 and 59 years (range 31-81) in Arm 2, and there were no significant clinical or pathologic differences between the arms. Median follow-up was 17 months (range 1-32). The negative predictive value (NPV) of AUS for identification of clinically significant axillary disease (> 2.0 mm) was 96.9%. No axillary recurrences have been observed in either arm. Conclusions Successful completion of the pilot phase of the randomized controlled trial confirms the feasibility of the study design, and provides prospective evidence supporting the ability of AUS to exclude clinically significant disease in the axilla. The results provide strong support for a phase 2 randomized controlled trial. PMID:27212005

  17. Contribution of Glottic Insufficiency to Perceived Breathiness in Classically Trained Singers.

    PubMed

    Graham, Ellen; Angadi, Vrushali; Sloggy, Joanna; Stemple, Joseph

    2016-09-01

    Breathiness in the singing voice is problematic for classical singers. Voice students and singing teachers typically attribute breathiness to breath management issues and breathing technique. The present study sought to determine whether glottic insufficiency may also contribute to breathiness in a singer's voice. Studies have revealed a relationship between insufficient vocal fold closure and inefficiency in the speaking voice. However, the effect of insufficient vocal fold closure on vocal efficiency in singers has yet to be determined. Two groups of voice students identified with and without breathiness issues underwent aerodynamic and acoustic voice assessment as well as laryngeal stroboscopy of the vocal folds to quantify the prevalence of insufficient vocal fold closure, also known as glottic insufficiency. These assessments revealed four groups: 1) those with glottic insufficiency and no perceived voice breathiness; 2) those with glottic sufficiency and perceived voice breathiness; 3) those with glottic insufficiency and perceived breathiness; and 4) those with glottic sufficiency and no perceived breathiness. Results suggest that previously undiscovered glottal insufficiency is common in young singers, particularly women, though the correlation with identified breathiness was not statistically significant. Acoustic and aerodynamic measures including noise-to-harmonics ratio, maximum phonation time, airflow rate, subglottal pressure, and laryngeal airway resistance were most sensitive to glottic insufficiency.

  18. Successful Completion of the Pilot Phase of a Randomized Controlled Trial Comparing Sentinel Lymph Node Biopsy to No Further Axillary Staging in Patients with Clinical T1-T2 N0 Breast Cancer and Normal Axillary Ultrasound.

    PubMed

    Cyr, Amy E; Tucker, Natalia; Ademuyiwa, Foluso; Margenthaler, Julie A; Aft, Rebecca L; Eberlein, Timothy J; Appleton, Catherine M; Zoberi, Imran; Thomas, Maria A; Gao, Feng; Gillanders, William E

    2016-08-01

    Axillary surgery is not considered therapeutic in patients with clinical T1-T2 N0 breast cancer. The importance of axillary staging is eroding in an era in which tumor biology, as defined by biomarker and gene expression profile, is increasingly important in medical decision making. We hypothesized that axillary ultrasound (AUS) is a noninvasive alternative to sentinel lymph node biopsy (SLNB), and AUS could replace SLNB without compromising patient care. Patients with clinical T1-T2 N0 breast cancer and normal AUS were eligible for enrollment. Subjects were randomized to no further axillary staging (arm 1) vs SLNB (arm 2). Descriptive statistics were used to describe the results of the pilot phase of the randomized controlled trial. Sixty-eight subjects were enrolled in the pilot phase of the trial (34 subjects in arm 1, no further staging; 32 subjects in arm 2, SLNB; and 2 subjects voluntarily withdrew from the trial). The median age was 61 years (range 40 to 80 years) in arm 1 and 59 years (range 31 to 81 years) in arm 2, and there were no significant clinical or pathologic differences between the arms. Median follow-up was 17 months (range 1 to 32 months). The negative predictive value (NPV) of AUS for identification of clinically significant axillary disease (>2.0 mm) was 96.9%. No axillary recurrences have been observed in either arm. Successful completion of the pilot phase of the randomized controlled trial confirms the feasibility of the study design, and provides prospective evidence supporting the ability of AUS to exclude clinically significant disease in the axilla. The results provide strong support for a phase 2 randomized controlled trial. Copyright © 2016 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

  19. pN0(i+) Breast Cancer: Treatment Patterns, Locoregional Recurrence, and Survival Outcomes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Karam, Irene; Breast Cancer Outcomes Unit, British Columbia Cancer Agency, Vancouver, BC; Lesperance, Maria F.

    Purpose: To examine treatment patterns, recurrence, and survival outcomes in patients with pN0(i+) breast cancer. Methods and Materials: Subjects were 5999 women with AJCC (6th edition) pT1-3, pN0-N1a, M0 breast cancer diagnosed between 2003 and 2006. Of these, 4342 (72%) had pN0, 96 (2%) had pN0(i+), 349 (6%) had pNmic (micrometastases >0.2 mm to ≤2 mm), and 1212 (20%) had pN1a (1-3 positive macroscopic nodes) disease. Treatment characteristics and 5-year Kaplan-Meier local recurrence, regional recurrence (RR), locoregional recurrence (LRR), and overall survival were compared between nodal subgroups. Multivariable analysis was performed using Cox regression modeling. A 1:3 case-match analysis examinedmore » outcomes in pN0(i+) cases compared with pN0 controls matched for similar tumor and treatment characteristics. Results: Median follow-up was 4.8 years. Adjuvant systemic therapy use increased with nodal stage: 81%, 92%, 95%, and 94% in pN0, pN0(i+), pNmic, and pN1a disease, respectively (P<.001). Nodal radiation therapy (RT) use also increased with nodal stage: 1.7% in pN0, 27% in pN0(i+), 33% in pNmic, and 63% in pN1a cohorts (P<.001). Five-year Kaplan-Meier outcomes in pN0 versus pN0(i+) cases were as follows: local recurrence 1.7% versus 3.7% (P=.20), RR 0.5% versus 2.2% (P=.02), and LRR 2.1% versus 5.8% (P=.02). There were no RR events in 26 patients with pN0(i+) disease who received nodal RT and 2 RR events in 70 patients who did not receive nodal RT. On multivariable analysis, pN0(i+) was not associated with worse locoregional control or survival. On case-match analysis, LRR and overall survival were similar between pN0(i+) and matched pN0 counterparts. Conclusions: Nodal involvement with isolated tumor cells is not a significant prognostic factor for LRR or survival in this study's multivariable and case-match analyses. These data do not support the routine use of nodal RT in the setting of pN0(i+) disease. Prospective studies are needed to define

  20. [A comparison between 3.0 T MRI and histopathology for preoperative T staging of potentially resectable esophageal cancer].

    PubMed

    Wang, Z Q; Zhang, F G; Guo, J; Zhang, H K; Qin, J J; Zhao, Y; Ding, Z D; Zhang, Z X; Zhang, J B; Yuan, J H; Li, H L; Qu, J R

    2017-03-21

    Objective: To explore the value of 3.0 T MRI using multiple sequences (star VIBE+ BLADE) in evaluating the preoperative T staging for potentially resectable esophageal cancer (EC). Methods: Between April 2015 and March 2016, a total of 66 consecutive patients with endoscopically proven resectable EC underwent 3.0T MRI in the Affiliated Cancer Hospital of Zhengzhou University.Two independent readers were assigned a T staging on MRI according to the 7th edition of UICC-AJCC TNM Classification, the results of preoperative T staging were compared and analyzed with post-operative pathologic confirmation. Results: The MRI T staging of two readers were highly consistent with histopathological findings, and the sensitivity, specificity and accuracy of preoperative T staging MR imaging were also very high. Conclusion: 3.0 T MRI using multiple sequences is with high accuracy for patients of potentially resectable EC in T staging. The staging accuracy of T1, T2 and T3 is better than that of T4a. 3.0T MRI using multiple sequences could be used as a noninvasive imaging method for pre-operative T staging of EC.

  1. Completeness of T, N, M and stage grouping for all cancers in the Mallorca Cancer Registry.

    PubMed

    Ramos, M; Franch, P; Zaforteza, M; Artero, J; Durán, M

    2015-11-04

    TNM staging of cancer is used to establish the treatment and prognosis for cancer patients, and also allows the assessment of screening programmes and hospital performance. Collection of staging data is becoming a cornerstone for cancer registries. The objective of the study was to assess the completeness of T, N, M and stage grouping registration for all cancers in the Mallorca Cancer Registry in 2006-2008 and to explore differences in T, N, M and stage grouping completeness by site, gender, age and type of hospital. All invasive cancer cases during the period 2006-2008 were selected. DCO, as well as children's cancers, CNS, unknown primary tumours and some haematological cases were excluded. T, N, M and stage grouping were collected separately and followed UICC (International Union Against Cancer) 7th edition guidelines. For T and N, we registered whether they were pathological or clinical. Ten thousand two hundred fifty-seven cases were registered. After exclusions, the study was performed with 9283 cases; 39.4 % of whom were women and 60.6 % were men. T was obtained in 48.6 % cases, N in 36.5 %, M in 40 % and stage in 37.9 %. T and N were pathological in 71 % of cases. Stage completeness exceeded 50 % in lung, colon, ovary and oesophagus, although T also exceeded 50 % at other sites, including rectum, larynx, colon, breast, bladder and melanoma. No differences were found in TNM or stage completeness by gender. Completeness was lower in younger and older patients, and in cases diagnosed in private clinics. T, N, M and stage grouping data collection in population-based cancer registries is feasible and desirable.

  2. Pre-emptive glottic enlargement before laryngotracheal surgery in patients at high risk for postoperative bilateral vocal fold paralysis.

    PubMed

    Schweiger, Thomas; Hoetzenecker, Konrad; Roesner, Imme; Schneider-Stickler, Berit; Denk-Linnert, Doris-Maria; Klepetko, Walter

    2018-02-01

    Bilateral vocal fold paralysis (VFP) is a severe complication after laryngotracheal (LT) surgery. The reduced glottic opening leads to significant respiratory distress immediately after the operation and requires the placement of a tracheostomy in most cases. Patients with a pre-existing unilateral VFP or expected recurrent nerve resection are at the highest risk for glottic failure. These patients might benefit from a pre-emptive glottic enlargement before LT surgery. We performed a retrospective review of patients who received a pre-emptive glottis enlargement before LT surgery at the Medical University of Vienna from October 2011 to December 2016. Peri- and postoperative outcomes of this strategy were analysed. Six patients underwent preparatory glottic enlargement prior to LT resection. Four patients had recurrent thyroid cancer, and 1 patient had thymic cancer invading the cervical airway. The remaining patient had a complex benign glotto/subglottic stricture complicated by a pre-existing bilateral VFP. All patients received oblique cricotracheal resections extending into the larynx [resection length 39 ± 7 mm (mean ± SD)]. Extubation within 24 h after surgery was achieved in 5 of 6 cases, although all patients had postoperative unilateral (n = 5) or bilateral (n = 1) VFP as anticipated. In 5 of the 6 patients, oral intake could be started immediately after the operation. The remaining patient regained full swallowing function after intensive swallowing rehabilitation. Postoperative voice quality was subjectively perceived as satisfactory by all patients. Pre-emptive glottic enlargement is a valuable treatment strategy in patients at highest risk for postoperative bilateral VFP. It facilitates immediate postoperative extubation, despite at least unilateral VFP and extensive LT surgical procedures. © The Author(s) 2018. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights

  3. Carr-Purcell-Meiboom-Gill (CPMG) Imaging of Prostate Cancer: Quantitative T2 Values for Cancer Discrimination

    PubMed Central

    Roebuck, Joseph R.; Haker, Steven J.; Mitsouras, Dimitris; Rybicki, Frank J.; Tempany, Clare M.; Mulkern, Robert V.

    2009-01-01

    Quantitative, apparent T2 values of suspected prostate cancer and healthy peripheral zone tissue in men with prostate cancer were measured using a Carr-Purcell-Meiboom-Gill (CPMG) imaging sequence in order to assess the cancer discrimination potential of tissue T2 values. The CPMG imaging sequence was used to image the prostates of 18 men with biopsy proven prostate cancer. Whole gland coverage with nominal voxel volumes of 0.54 × 1.1 × 4 mm3 was obtained in 10.7 minutes, resulting in data sets suitable for generating high quality images with variable T2-weighting and for evaluating quantitative T2 values on a pixel-by-pixel basis. Region-of-interest analysis of suspected healthy peripheral zone tissue and suspected cancer, identified on the basis of both T1- and T2-weighted signal intensities and available histopathology reports, yielded significantly (p < 0.0001) longer apparent T2 values in suspected healthy tissue (193 ± 49 ms) vs. suspected cancer (100 ± 26 ms), suggesting potential utility of this method as a tissue specific discrimination index for prostate cancer. We conclude that CPMG imaging of the prostate can be performed in reasonable scan times and can provide advantages over T2-weighted fast spin echo imaging alone, including quantitative T2 values for cancer discrimination as well as proton density maps without the point spread function degradation associated with short effective echo time fast spin echo (FSE) sequences. PMID:18823731

  4. Predictive criteria for prostate cancer detection in men with serum PSA concentration of 2.0 to 4.0 ng/mL.

    PubMed

    Kravchick, Sergey; Peled, Ronit; Dorfman, Dov; Agulansky, Leonid; Ben-Dor, David; Cytron, Shmuel

    2005-09-01

    To assess the usefulness of measuring testosterone, free testosterone, and the free/total (f/t) prostate-specific antigen (PSA) ratio with the intention of reducing the number of unnecessary biopsies in the patients with PSA values between 2.0 and 4.0 ng/mL. Cancer detection is not rare among patients with PSA values between 2.0 and 4.0 ng/mL. A total of 171 men with serum PSA levels of 2.0 to 4.0 ng/mL were enrolled in this study. The f/t PSA ratio and total and free testosterone levels were quantified. All patients underwent transrectal ultrasound-guided biopsy. The cancer detection rate, clinical and pathologic features of the cancers detected, and the probability of cancer detection in relation to the f/t PSA ratio and total and free testosterone levels were estimated. Two-step statistical analysis was used for descriptive purposes and in the detection of cancer predictors. Statistical significance was set at P < or = 0.05. The mean patient age was 63.3 years. Cancer was detected in 39 (22.8%) of the 171 patients. Only 15.4% of our patients had insignificant cancer. The f/t PSA ratio and total and free testosterone levels were significantly lower in the patients with prostate cancer (19.3%, 13.68 nmol/L, and 28.4 pmol/L, respectively; P < 0.001). The f/t PSA ratio and free testosterone were the strongest predictors of cancer detection (P < 0.001). The results of our study have shown that an important number of cancers could be detected in the PSA range of 2.0 to 4.0 ng/mL. The great majority of cancers detected have the features of medically significant tumors. The combination of the f/t PSA ratio and free testosterone measurements may reveal those patients who require biopsy.

  5. Clinical radiobiology of stage T2-T3 bladder cancer.

    PubMed

    Majewski, Wojciech; Maciejewski, Boguslaw; Majewski, Stanislaw; Suwinski, Rafal; Miszczyk, Leszek; Tarnawski, Rafal

    2004-09-01

    To evaluate the relationship between total radiation dose and overall treatment time (OTT) with the treatment outcome, with adjustment for selected clinical factors, in patients with Stage T2-T3 bladder cancer treated with curative radiotherapy (RT). The analysis was based on 480 patients with Stage T2-T3 bladder cancer who were treated at the Center of Oncology in Gliwice between 1975 and 1995. The mean total radiation dose was 65.5 Gy, and the mean OTT was 51 days. In 261 patients (54%), planned and unplanned gaps occurred during RT. Four fractionation schedules were used: (1) conventional fractionation (once daily, 1.8-2.5 Gy/fraction); (2) protracted fractionation (pelvic RT, once daily, 1.6-1.7 Gy/fraction, boost RT, once daily, 2.0 Gy/fraction); (3) accelerated hyperfractionated boost (pelvic RT, once daily, 2.0 Gy/fraction; boost RT, twice daily, 1.3-1.4 Gy/fraction); and (4) accelerated hyperfractionation (pelvic and boost RT, twice daily, 1.2-1.5 Gy/fraction). In all fractionation schedules, the total radiation dose was similar (average 65.5 Gy), but the OTT was different (mean 53 days for conventional fractionation, 62 days for protracted fractionation, 45 days for accelerated hyperfractionated boost, and 41 days for accelerated hyperfractionation). A Cox proportional hazard model and maximum likelihood logistic model were used to evaluate the relationship between the treatment-related parameters (total radiation dose, dose per fraction, and OTT) and clinical factors (clinical T stage, hemoglobin level and bladder capacity before RT) and treatment outcome. With a median follow-up of 76 months, the actuarial 5-year local control rate was 47%, and the overall survival rate was 40%. The logistic analysis, which included the total dose, OTT, and T stage, revealed that all of these factors were significantly related to tumor control probability (p = 0.021 for total radiation dose, p = 0.038 for OTT, and p = 0.00068 for T stage). A multivariate Cox model, which

  6. Effect of mandibular tori on glottic exposure during simulated suspension microlaryngoscopy.

    PubMed

    Best, Simon R; Kobler, James B; Friedman, Aaron D; Barbu, Anca M; Zeitels, Steven M; Burns, James A

    2014-03-01

    Mandibular tori have been identified as a contributing factor in difficult exposure during intubation. However, no investigation has measured the effect of mandibular tori on glottic exposure during suspension microlaryngoscopy (SML). The objective of this study was to measure how the size and location of mandibular tori affect glottic exposure during simulated SML at different thyromental distances. Suspension microlaryngoscopy was modeled on an anatomically accurate skull and larynx with thyromental distances between 6 and 12 cm. Mandibular tori were simulated by protruding screws 5 to 15 mm from the lingual aspect of the mandible. The tori were positioned either 15 mm (anterior) or 25 mm (posterior) from the midline of the symphysis. The glottic exposure for the various-size tori in each location was measured by recording the displacement of the glottiscope tip relative to the most anterior exposure achievable without tori. The glottiscope angle relative to the horizontal plane was measured for each condition. Mandibular tori of more than 10 mm had a significant impact on glottic exposure. Displacement of the glottiscope tip ranged from 2 to 9 mm for anteriorly placed tori and from 7 to 29 mm for posteriorly placed tori, with larger tori causing greater displacement. Increasing the thyromental distance increased the posterior glottiscope tip displacement regardless of torus size or location. The glottiscope angle increased with larger tori (12º to 28º), but this angle did not change with increasing thyromental distance. Larger size and more-posterior location of mandibular tori more significantly reduce glottic exposure during SML. The inner table of the mandible is the most relevant anatomic constraint on glottic exposure, which varies with the presence or absence of mandibular tori independent of thyromental distance.

  7. Glottic Closing Force Versus Laryngeal Adductory Pressure in the Canine Larynx.

    PubMed

    Paniello, Randal C; Bhatt, Neel K

    2017-03-01

    The strength of glottic closure with recurrent laryngeal nerve (RLN) stimulation has been indirectly measured experimentally by determining the squeezing pressure on a balloon inserted between the vocal folds, termed laryngeal adductory pressure (LAP). In this study, we sought to measure glottic closing force (GCF) directly and compare these results to LAP measures obtained with identical stimulation parameters. In canines, a method for measuring GCF was developed in which a suture was looped through a lateral thyrotomy hole, around the vocal process and back, then attached to a force gauge. The RLN was maximally stimulated and GCF recorded. The LAP was then measured as previously described, using the same stimuli. This process was repeated at 9 stimulation frequencies in 10-Hz intervals from 20 to 100 Hz. The GCF and LAP were compared using Pearson's correlation coefficient (PCC). Both sides were measured in 16 dogs, resulting in 32 data sets. The LAP measures were obtained at all frequencies, while GCF was obtained in 246 of 288 (85.4%) attempts. The maximum GCF for each dog typically occurred at 80 to 100 Hz and averaged 0.287 ± 0.106 newtons. Plotting GCF versus LAP for each hemilaryngeal preparation, the mean PCC was 0.932 ± .042 (range, 0.802-0.987). The mean PCC did not differ between control (n = 26) and postoperative (n = 6) hemilarynges. This method for measuring GCF appears valid. The high Pearson's correlation coefficient indicates strong covariance between GCF and LAP, demonstrating that they are both measures of the same physical property. The LAP is easier to perform and more consistently obtained.

  8. Oncologic Safety of Local Excision Compared With Total Mesorectal Excision for ypT0-T1 Rectal Cancer: A Propensity Score Analysis.

    PubMed

    Jung, Sung Min; Yu, Chang Sik; Park, In Ja; Kim, Tae Won; Kim, Jong Hoon; Yoon, Yong Sik; Lim, Seok-Byung; Kim, Jin Cheon

    2016-05-01

    Good oncologic outcomes, demonstrated by a complete pathologic response after preoperative chemoradiotherapy (PCRT), have led to local excision (LE) in selected patients with rectal cancer. We evaluated the oncologic safety of LE compared with total mesorectal excision (TME) in patients with ypT0-T1 rectal cancer.A retrospective review of 304 patients who underwent PCRT, followed by LE or TME, for ypT0-T1 rectal cancer was performed. Propensity scores were computed and used to match groups (LE:TME = 1:1), and analysis of disease-free survival (DFS) and overall survival (OS) was made by comparing patients who underwent LE or TME. Prognostic factors of relapse were analyzed for all patients.Tumor categories were ypT0 in 25 (61.9%) cases, ypTis in 6 (14.3%) cases, and ypT1 in 11 (26.2%) cases for the LE group, and ypT0 in 28 (66.7%) cases, ypTis in 4 (9.5%) cases, and ypT1 in 10 (23.8%) cases for the matched TME patients. There was no significant difference between the matched LE and TME groups in relapse (4.8% and 7.14%, respectively; P = 0.646), 5-year DFS (95.2% vs 91.6%; P = 0.33) and 5-year OS (96.6% vs 88.0%; P = 0.238). In the multivariate Cox regression analysis, tumor distance from the anal verge (hazard ratio [HR] = 0.78; 95% confidence interval (CI) = 0.616-0.992) and the tumor grade (HR = 4.29; 95% CI = 1.430-12.886) were significantly associated with the recurrence risk.LE results in oncologic outcomes that are comparable to those achieved by TME in selected patients with ypT0-T1 rectal cancer after PCRT.

  9. Web thickness determines the therapeutic effect of endoscopic keel placement on anterior glottic web.

    PubMed

    Chen, Jian; Shi, Fang; Chen, Min; Yang, Yue; Cheng, Lei; Wu, Haitao

    2017-10-01

    This work is a retrospective analysis to investigate the critical risk factor for the therapeutic effect of endoscopic keel placement on anterior glottic web. Altogether, 36 patients with anterior glottic web undergoing endoscopic lysis and silicone keel placement were enrolled. Their voice qualities were evaluated using the voice handicap index-10 (VHI-10) questionnaire, and improved significantly 3 months after surgery (21.53 ± 3.89 vs 9.81 ± 6.68, P < 0.0001). However, 10 (27.8%) cases had web recurrence during the at least 1-year follow-up. Therefore, patients were classified according to the Cohen classification or web thickness, and the recurrence rates were compared. The distribution of recurrence rates for Cohen type 1 ~ 4 were 28.6, 16.7, 33.3, and 40%, respectively. The difference was not statistically significant (P = 0.461). When classified by web thickness, only 2 of 27 (7.41%) thin type cases relapsed whereas 8 of 9 (88.9%) cases in the thick group reformed webs (P < 0.001). These results suggest that the therapeutic outcome of endoscopic keel placement mostly depends on the web thickness rather than the Cohen grades. Endoscopic lysis and keel placement is only effective for cases with thin glottic webs. Patients with thick webs should be treated by other means.

  10. Tumor location is a strong predictor of tumor progression and survival in T2 gallbladder cancer: an international multicenter study

    PubMed Central

    Shindoh, Junichi; de Aretxabala, Xabier; Aloia, Thomas A.; Carlos Roa, Juan; Zimmitti, Giuseppe; Javle, Milind; Conrad, Claudius; Maru, Dipen M.; Aoki, Taku; Vigano, Luca; Ribero, Dario; Roa, Ivan; Kokudo, Norihiro; Capussotti, Lorenzo; Vauthey, Jean-Nicolas

    2016-01-01

    Objective To determine the prognostic impact of tumor location in gallbladder cancer. Summary Background Data Depth of tumor is a strong predictor of survival after curative resection of gallbladder cancer. However, the gallbladder has a unique anatomical relationship with the liver, and the clinical significance of tumor location remains unclear. Methods For 437 patients with gallbladder cancer resected at 4 international institutions, clinicopathologic characteristics and their association with survival were analyzed. Tumor location was defined as “hepatic side” or “peritoneal side”, and the prognostic significance of tumor location was evaluated. Results Among the 252 patients with T2 disease, patients with tumors on the hepatic side (T2h, n=99) had higher rates of vascular invasion, neural invasion, and nodal metastasis than patients with tumors on the peritoneal side (T2p, n=153) (51% vs. 19%, 33% vs. 8%, and 40% vs. 17%, respectively, P<0.01 for all). After a median follow-up of 58.9 months, 3-year and 5-year survival rates were 52.1% and 42.6%, respectively, for T2h tumors and 73.7% and 64.7%, respectively, for T2p tumors (P=0.0006). No such differences were observed in T1 or T3 tumors. Multivariate analysis confirmed the independent association of hepatic-side location with survival in T2 tumors (hazard ratio, 2.7; 95% CI, 1.7 to 4.2; P<0.001). This subclassification of T2 tumors predicted recurrence in the liver (23% vs. 3%, P=0.003) and distant lymph nodes (16% vs. 3%, P=0.019) even after radical resection. Conclusions After curative resection of T2 gallbladder cancer, tumor location predicts the pattern of recurrence and survival. PMID:24854451

  11. Tumor location is a strong predictor of tumor progression and survival in T2 gallbladder cancer: an international multicenter study.

    PubMed

    Shindoh, Junichi; de Aretxabala, Xabier; Aloia, Thomas A; Roa, Juan Carlos; Roa, Ivan; Zimmitti, Giuseppe; Javle, Milind; Conrad, Claudius; Maru, Dipen M; Aoki, Taku; Vigano, Luca; Ribero, Dario; Kokudo, Norihiro; Capussotti, Lorenzo; Vauthey, Jean-Nicolas

    2015-04-01

    To determine the prognostic impact of tumor location in gallbladder cancer. Depth of tumor is a strong predictor of survival after curative resection of gallbladder cancer. However, the gallbladder has a unique anatomical relationship with the liver, and the clinical significance of tumor location remains unclear. For 437 patients with gallbladder cancer who underwent resection at 4 international institutions, clinicopathologic characteristics and their association with survival were analyzed. Tumor location was defined as "hepatic side" or "peritoneal side," and the prognostic significance of tumor location was evaluated. Among the 252 patients with T2 disease, patients with tumors on the hepatic side (T2h, n = 99) had higher rates of vascular invasion, neural invasion, and nodal metastasis than patients with tumors on the peritoneal side (T2p, n = 153) (51% vs 19%, 33% vs 8%, and 40% vs 17%, respectively; P < 0.01 for all). After a median follow-up of 58.9 months, 3-year and 5-year survival rates were 52.1% and 42.6%, respectively, for T2h tumors and 73.7% and 64.7%, respectively, for T2p tumors (P = 0.0006). No such differences were observed in T1 or T3 tumors. Multivariate analysis confirmed the independent association of hepatic-side location with survival in T2 tumors (hazard ratio, 2.7; 95% confidence interval, 1.7-4.2; P < 0.001). This subclassification of T2 tumors predicted recurrence in the liver (23% vs 3%; P = 0.003) and distant lymph nodes (16% vs 3%; P = 0.019) even after radical resection. After curative resection of T2 gallbladder cancer, tumor location predicts the pattern of recurrence and survival.

  12. Carr-Purcell-Meiboom-Gill imaging of prostate cancer: quantitative T2 values for cancer discrimination.

    PubMed

    Roebuck, Joseph R; Haker, Steven J; Mitsouras, Dimitris; Rybicki, Frank J; Tempany, Clare M; Mulkern, Robert V

    2009-05-01

    Quantitative, apparent T(2) values of suspected prostate cancer and healthy peripheral zone tissue in men with prostate cancer were measured using a Carr-Purcell-Meiboom-Gill (CPMG) imaging sequence in order to assess the cancer discrimination potential of tissue T(2) values. The CPMG imaging sequence was used to image the prostates of 18 men with biopsy-proven prostate cancer. Whole gland coverage with nominal voxel volumes of 0.54 x 1.1 x 4 mm(3) was obtained in 10.7 min, resulting in data sets suitable for generating high-quality images with variable T(2)-weighting and for evaluating quantitative T(2) values on a pixel-by-pixel basis. Region-of-interest analysis of suspected healthy peripheral zone tissue and suspected cancer, identified on the basis of both T(1)- and T(2)-weighted signal intensities and available histopathology reports, yielded significantly (P<.0001) longer apparent T(2) values in suspected healthy tissue (193+/-49 ms) vs. suspected cancer (100+/-26 ms), suggesting potential utility of this method as a tissue specific discrimination index for prostate cancer. We conclude that CPMG imaging of the prostate can be performed in reasonable scan times and can provide advantages over T(2)-weighted fast spin echo (FSE) imaging alone, including quantitative T(2) values for cancer discrimination as well as proton density maps without the point spread function degradation associated with short effective echo time FSE sequences.

  13. Estimation of T2* Relaxation Time of Breast Cancer: Correlation with Clinical, Imaging and Pathological Features

    PubMed Central

    Seo, Mirinae; Jahng, Geon-Ho; Sohn, Yu-Mee; Rhee, Sun Jung; Oh, Jang-Hoon; Won, Kyu-Yeoun

    2017-01-01

    Objective The purpose of this study was to estimate the T2* relaxation time in breast cancer, and to evaluate the association between the T2* value with clinical-imaging-pathological features of breast cancer. Materials and Methods Between January 2011 and July 2013, 107 consecutive women with 107 breast cancers underwent multi-echo T2*-weighted imaging on a 3T clinical magnetic resonance imaging system. The Student's t test and one-way analysis of variance were used to compare the T2* values of cancer for different groups, based on the clinical-imaging-pathological features. In addition, multiple linear regression analysis was performed to find independent predictive factors associated with the T2* values. Results Of the 107 breast cancers, 92 were invasive and 15 were ductal carcinoma in situ (DCIS). The mean T2* value of invasive cancers was significantly longer than that of DCIS (p = 0.029). Signal intensity on T2-weighted imaging (T2WI) and histologic grade of invasive breast cancers showed significant correlation with T2* relaxation time in univariate and multivariate analysis. Breast cancer groups with higher signal intensity on T2WI showed longer T2* relaxation time (p = 0.005). Cancer groups with higher histologic grade showed longer T2* relaxation time (p = 0.017). Conclusion The T2* value is significantly longer in invasive cancer than in DCIS. In invasive cancers, T2* relaxation time is significantly longer in higher histologic grades and high signal intensity on T2WI. Based on these preliminary data, quantitative T2* mapping has the potential to be useful in the characterization of breast cancer. PMID:28096732

  14. Vocal characteristics of congenital anterior glottic webs in children: A case report.

    PubMed

    Shah, Jay; White, Katherine; Dohar, Joseph

    2015-06-01

    This case report describes a 5-year-old girl with chronic dysphonia and high-pitched voice since birth. Vocal quality was noted to be harsh. Videostroboscopy revealed significant hyperfunction and a Type II congenital anterior glottic web. Endoscopic division of the anterior glottic web was performed with significant improvement in vocal quality and quality of life. This paper describes methods of analyzing, diagnosing, and treating anterior glottic web with a focus on quality of life. Also, unique acoustic and aerodynamic voice features are identified. No other descriptions of a voice characteristic for anterior glottic web currently exist in the literature. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. Exclusive low-dose-rate brachytherapy in 279 patients with T2N0 mobile tongue carcinoma

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bourgier, Celine; Coche-Dequeant, Bernard; Fournier, Charles

    2005-10-01

    Purpose: To evaluate the therapeutic results obtained with {sup 192}Ir low-dose-rate interstitial brachytherapy in T2N0 mobile tongue carcinoma. Patients and Methods: Between December 1979 and January 1998, 279 patients with T2N0 mobile tongue carcinoma were treated by exclusive low-dose-rate brachytherapy, with or without neck dissection. {sup 192}Ir brachytherapy was performed according to the 'Paris system' with a median total dose of 60 Gy (median dose rate, 0.5 Gy/h). Results: Overall survival was 74.3% and 46.6% at 2 and 5 years. Local control was 79.1% at 2 years and regional control, respectively, 75.9% and 69.5% at 2 and 5 years (Kaplan-Meiermore » method). Systematic dissection revealed 44.6% occult node metastases, and histologic lymph node involvement was identified as the main significant factor for survival. Complication rate was 16.5% (Grade 3, 2.9%). Half of the patients presented previous and/or successive malignant tumor (ear-nose-throat, esophagus, or bronchus). Conclusion: Exclusive low-dose-rate brachytherapy is an effective treatment for T2 tongue carcinoma. Regional control and survival are excellent in patients undergoing systematic neck dissection, which is mandatory in our experience because of a high rate of occult lymph node metastases.« less

  16. Glottic airway gain after 'suture arytenoid laterofixation' in bilateral vocal cord paralysis.

    PubMed

    Korkmaz, Mehmet Hakan; Bayır, Ömer; Tatar, Emel Çadallı; Saylam, Güleser; Öcal, Bülent; Keseroğlu, Kemal; Özdek, Ali

    2015-09-01

    This method is an easy, non-expensive, and effective technique in bilateral vocal cord paralysis to improve glottic airway and clinical performance. To evaluate the effectiveness of 'suture arytenoid laterofixation' surgery in bilateral vocal cord paralysis. A retrospective analysis of patients' medical history undergoing 'suture arytenoid laterofixation' surgery for bilateral vocal cord paralysis. This technique was applied under general anesthesia with both microlaryngoscopy and video-monitoring. Two 16 g needles and one 1/0 nylon thread were used for the procedure with 1 cm skin incision; no tracheotomy or tissue excision was required. Pre-post-operative photographs of the glottic region were taken from the endoscopic records, and the areas of rima glottis openings were calculated with the Image-J programme. Forty-seven patients were analyzed. The mean pre-post-operative rima glottis areas were 1.11 ± 0.56 and 2.24 ± 0.93 mm(2), respectively (p < 0.001). Five patients with previous tracheotomy were decannulated within a few days after the operation. In three patients, mild complications developed in the early post-operative period (two laryngeal edemas, one submucosal hematoma). Tracheotomy was performed to only one pregnant patient in the post-operative first day. None of the patients had granulation formation or synechia.

  17. Performance Comparison of 1.5 T Endorectal Coil MRI with Non-Endorectal Coil 3.0 T MRI in Patients with Prostate Cancer

    PubMed Central

    Shah, Zarine K.; Elias, Saba N.; Abaza, Ronney; Zynger, Debra L.; DeRenne, Lawrence A.; Knopp, Michael V.; Guo, Beibei; Schurr, Ryan; Heymsfield, Steven B.; Jia, Guang

    2015-01-01

    Rationale and Objectives To compare prostate morphology, image quality, and diagnostic performance of 1.5 T endorectal coil MRI and 3.0 T non-endorectal coil MRI in patients with prostate cancer. Materials and Methods MR images obtained of 83 patients with prostate cancer using 1.5 T MRI systems with an endorectal coil were compared to images collected from 83 patients with a 3.0 T MRI system. Prostate diameters were measured and image quality was evaluated by one ABR-certified radiologist (Reader 1) and one ABR-certified diagnostic medical physicist (Reader 2). The likelihood of the peripheral zone cancer presence in each sextant and local extent were rated and compared with histopathologic findings. Results Prostate anterior-posterior diameter measured by both readers was significantly shorter with 1.5 T endorectal MRI than with 3.0 T MRI. The overall image quality score difference was significant only for Reader 1. Both readers found that the two MRI systems provided similar diagnostic accuracy in cancer localization, extraprostatic extension, and seminal vesicle involvement. Conclusion Non-endorectal coil 3.0 T MRI provides prostate images that are natural in shape and that have comparable image quality to those obtained at 1.5 T with an endorectal coil, but not superior diagnostic performance. These findings suggest an opportunity exists for improving technical aspects of 3.0 T prostate MRI. PMID:25579637

  18. Prognostic factors in clinical T1N0M0 thoracic esophageal squamous cell carcinoma invading the muscularis mucosa or submucosa.

    PubMed

    Uchinami, Yusuke; Myojin, Miyako; Takahashi, Hiroaki; Harada, Keiichi; Shimizu, Shinichi; Hosokawa, Masao

    2016-06-21

    Multimodality treatment is widely performed for clinical T1N0M0 (UICC-TNM classification, 7th edition) thoracic esophageal squamous cell carcinoma (ESCC), but available articles regarding treatment results are limited. This study assessed the outcomes of clinical T1N0M0 thoracic ESCC invading the muscularis mucosa (MM) or submucosa (SM) treated with radiotherapy (RT) or chemoradiotherapy (CRT). We retrospectively reviewed the medical charts of 90 patients with clinical T1N0M0 thoracic ESCC treated with RT or CRT in our hospital in 2004-2011. Of these 90 patients, we analyzed the cases of 71 patients who met our inclusion criteria. All 71 patients had MM or SM cancer. In the 47 patients treated with CRT, the chemotherapy regimen of 5-fluorouracil (5-FU) plus cisplatin (CDDP) was used for 46 patients and 5-FU and nedaplatin was used for one patient. Forty-five patients underwent endoscopic resection (ER) followed by RT or CRT as an additional treatment. Elective nodal irradiation (ENI) was used in 39 patients. For all analyses, statistical significance was defined as 0.05, and the Bonferroni correction was used for the multivariate analysis. The median age was 70 years (range 47-84). With a median follow-up of 43.6 months (range 1.5-124.2), the 5-year overall survival (OS), disease-specific survival (DSS) and disease-free survival (DFS) rates were 64.0, 72.8 and 50.0 %, respectively. The multivariate analysis showed that performance status (PS) was an independent prognostic factors for DSS and DFS (DSS, p < 0.001; DFS, p < 0.001). Chemotherapy in addition to RT showed a trend for better DSS (p = 0.032) but was not significant following Bonferroni correction. ER and ENI were not significant predictive factors for DSS and DFS. PS was an independent prognostic factor for DSS and DFS. ER and ENI had no significant relationship with DSS or DFS. The present results may be helpful in treatment decisions for clinical T1N0M0 thoracic ESCC.

  19. Thermonuclear Reaction Rate of T(t,2n) α Measured in ICF Plasmas

    NASA Astrophysics Data System (ADS)

    Brune, C. R.; Casey, D. T.; Caggiano, J. A.; Hatarik, R.; McNabb, D. P.; Sayre, D. B.; Smalyuk, V. A.; Bacher, A. D.; Frenje, J. A.; Gatu-Johnson, M.; Zylstra, A. B.; Couder, M.

    2014-09-01

    Measurements of charged-particle reactivity have been performed in inertial confinement fusion experiments at the National Ignition Facility. Time-of-flight detectors were used to measure neutrons from the T(t,2n) and T(d,n) reactions produced by implosions with tritium-filled targets (0.1% deuterium). Along with the measured target fuel composition and reactant ion temperature, the well-known T(d,n) reactivity was used to convert the measured neutron yields into a T(t,2n) reactivity. The ion temperature was determined to be 3.3(3) keV, corresponding to an effective energy of 16 keV. In comparison to accelerator measurements of the low-energy T(t,2n) cross section, the source of all previous data, our experiment has resulted in T(t,2n) data with better statistics and lower backgrounds.

  20. Uniport versus multiport video-assisted thoracoscopic surgery in the perioperative treatment of patients with T1-3N0M0 non-small cell lung cancer: a systematic review and meta-analysis.

    PubMed

    Yang, Xinyu; Li, Ming; Yang, Xiaodong; Zhao, Mengnan; Huang, Yiwei; Dai, Xiyu; Jiang, Tian; Feng, Mingxiang; Zhan, Cheng; Wang, Qun

    2018-04-01

    Uniport video-assisted thoracoscopic surgery (VATS) has emerged as a less invasive approach for the treatment of non-small cell lung cancer (NSCLC). However, whether uniport VATS has more potential advantages over multiport VATS remains controversial. This meta-analysis aimed to compare the perioperative efficacy of uniport and multiport VATS for T1-3N0M0 NSCLC. An electronic and manual search of literature published before 1st October 2017 was conducted using PubMed, Embase, Web of Science, and the Wiley Online library. The effective values of dichotomous variables or continuous variables were estimated by odds ratios (OR) or by standardized mean differences (SMD) with 95% confidence intervals (CIs) respectively. Eleven relevant observational studies were included for meta-analysis. Results demonstrated that patients in the uniport group had a significant reduction in the duration of postoperative drainage (uniport: 4.39±2.48 vs. multiport: 4.99±3.24 days; P=0.003), bleeding volume (97.7±60.0 vs. 116.7±99.7 mL; P=0.006), length of hospital stay (6.3±2.4 vs. 7.0±3.6 days; P<0.001), VAS of postoperative pain (2.53±0.73 vs. 4.22±0.71, P=0.02) and in the overall rate of complications (14.5% vs. 17.5%; P=0.008). There were no significant differences between the two treatment groups with regards to mortality, operative time, the number of dissected lymph nodes or the conversion rate. Uniport VATS might have represent a preferable option for the treatment of T1-3N0M0 NSCLC, due to its superior perioperative efficacy.

  1. Study of the Histopathologic Characteristics and Surface Morphologies of Glottic Carcinomas With Anterior Vocal Commissure Involvement.

    PubMed

    Wu, Jianhui; Zhao, Jing; Wang, Zhangfeng; Li, Zenghong; Luo, Jie; Liao, Bing; Yang, Zhiyun; Liu, Qihong; Wang, Bin; Wen, Weiping; Lei, Wenbin

    2015-07-01

    This article explores the features and the role of the anterior vocal commissure (AVC) structure and the surface morphologies of glottic carcinomas with AVC involvement to provide a reference for the selection of transoral carbon dioxide (CO2) laser surgery. A total of 31 cases of glottic carcinomas with AVC involvement from May 2012 to January 2014 were included. All patients underwent electronic laryngoscopic examinations and computed tomography scans to determine the surface morphology. After surgery, the tumor specimens were resected integrally, and axial serial sections parallel to the plane of vocal cords were taken to explore the features and possible invasion paths of the glottic carcinomas with AVC involvement. The rates of involvement of the supraglottis and subglottis were 71.4% and 14.8%, respectively, via the AVC. The involvement of the superficial layer of the unilateral or bilateral vocal cords without involvement of the vocal muscle in the AVC region (IVM) or the cartilage was present in 15 cases (48.4%). The involvement of the superficial layer of the unilateral and bilateral vocal cords occurred in 16 cases (51.6%) with the IVM in 13 cases and the involvement of the intermediate lamina of the thyroid cartilage (ITC) in 8 cases. The involvement of the ITC was associated with the involvement of the vocal muscle of the AVC region (P < 0.05). Among the pushing carcinomas, 15 of 21 (71.4%) presented with well-defined tumor mass, and 8 of 10 (80.0%) infiltrating carcinomas presented with multiple tumor nests that were often surrounded by fibrosis (P < 0.05). The AVC is an important path of invasion of subglottic in glottic carcinomas but less so for suparglottic. The Broyles' ligaments acted as a barrier against the spread of the tumors to the thyroid cartilage, but this role was obviously weaken by the involvement of the vocal muscle of the AVC region. The infiltrating carcinomas presented with multiple tumor nests in fibrous tissue. When CO2 laser

  2. Randomized Trial of Hyperfractionation Versus Conventional Fractionation in T2 Squamous Cell Carcinoma of the Vocal Cord (RTOG 9512)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Trotti, Andy, E-mail: andy.trotti@moffitt.org; Zhang, Qiang; Bentzen, Søren M.

    2014-08-01

    Purpose: To compare hyperfractionation versus standard fractionation for T2N0 vocal cord carcinoma in a randomized controlled trial. Methods and Materials: Patients with T2 vocal cord cancer were stratified by substage (T2a vs T2b) and randomly assigned to receive either hyperfractionation (HFX) to 79.2 Gy in 66 fractions of 1.2 Gy given twice a day, or standard fractionation (SFX) to 70 Gy in 35 fractions given once a day. The trial was designed to detect a 55% reduction in the local failure hazard rate with 80% statistical power. Results: Between April 1996 and July 2003, a total of 250 patients were enrolled. Of 239more » patients analyzable for outcomes, 94% were male, 83% had a Karnofsky performance status of 90-100, and 62% had T2a tumor. Median follow-up for all surviving patients was 7.9 years (range, 0.6-13.1 years). The 5-year local control (LC) rate was 8 points higher but not statistically significant (P=.14 for HFX [78%] vs SFX [70%]), corresponding to a 30% hazard rate reduction. The 5-year disease-free survival (DFS) was 49% versus 40% (P=.13) and overall survival (OS) was 72% versus 63% (P=.29). HFX was associated with higher rates of acute skin, mucosal, and laryngeal toxicity. Grade 3-4 late effects were similar with a 5-year cumulative incidence of 8.5% (3.4%-13.6%) after SFX and 8.5% (3.4%-13.5%) after HFX. Conclusions: The 5-year local control was modestly higher with HFX compared to SFX for T2 glottic carcinoma, but the difference was not statistically significant. These results are consistent with prior studies of hyperfractionation showing a benefit in local control. Substaging by T2a versus T2b carries prognostic value for DFS and OS. For cost and convenience reasons other altered fractionation schedules have been adopted in routine practice.« less

  3. [Optimization of diagnosis indicator selection and inspection plan by 3.0T MRI in breast cancer].

    PubMed

    Jiang, Zhongbiao; Wang, Yunhua; He, Zhong; Zhang, Lejun; Zheng, Kai

    2013-08-01

    To optimize 3.0T MRI diagnosis indicator in breast cancer and to select the best MRI scan program. Totally 45 patients with breast cancers were collected, and another 35 patients with benign breast tumor served as the control group. All patients underwent 3.0T MRI, including T1- weighted imaging (T1WI), fat suppression of the T2-weighted imaging (T2WI), diffusion weighted imaging (DWI), 1H magnetic resonance spectroscopy (1H-MRS) and dynamic contrast enhanced (DCE) sequence. With operation pathology results as the gold standard in the diagnosis of breast diseases, the pathological results of benign and malignant served as dependent variables, and the diagnostic indicators of MRI were taken as independent variables. We put all the indicators of MRI examination under Logistic regression analysis, established the Logistic model, and optimized the diagnosis indicators of MRI examination to further improve MRI scan of breast cancer. By Logistic regression analysis, some indicators were selected in the equation, including the edge feature of the tumor, the time-signal intensity curve (TIC) type and the apparent diffusion coefficient (ADC) value when b=500 s/mm2. The regression equation was Logit (P)=-21.936+20.478X6+3.267X7+ 21.488X3. Valuable indicators in the diagnosis of breast cancer are the edge feature of the tumor, the TIC type and the ADC value when b=500 s/mm2. Combining conventional MRI scan, DWI and dynamic enhanced MRI is a better examination program, while MRS is the complementary program when diagnosis is difficult.

  4. Impact of postmastectomy radiotherapy in T3N0 invasive carcinoma of the breast: a Surveillance, Epidemiology, and End Results database analysis.

    PubMed

    McCammon, Robert; Finlayson, Christina; Schwer, Amanda; Rabinovitch, Rachel

    2008-08-15

    Randomized trials provide evidence for improved outcomes with postmastectomy radiotherapy (PMRT) in high-risk patients. It has been suggested that patients with T3N0 breast cancer represent a favorable subgroup for which PMRT renders little benefit. In the current study, the authors used a United States population database to evaluate PMRT in this subgroup. The cause-specific survival (CSS) and overall survival (OS) of women with T3N0M0 breast cancer in the Surveillance, Epidemiology, and End Results database after mastectomy and axillary staging from 1988 to 2002 were analyzed. Univariate analysis was performed to relate CSS with PMRT (yes vs no), tumor size (< or =7 cm vs >7 cm), grade (1 vs 2 or 3), patient age (< or =50 years vs >50 years), the number of lymph nodes dissected (< or =13 vs >13), and the era treated (1988-1997 vs 1998-2002). Multivariate analyses for CSS and OS were also performed. In total, 1865 women met the analysis criteria for OS; CSS data were available for 98.8% of those women. Of the women who were diagnosed during the era from 1988 to 1997, 22% received PMRT, and that rate increased to 41% during the era from 1998 to 2002. The actuarial 10-year CSS for those who received PMRT versus those who did not receive PMRT was 81.6% versus 79.8%, respectively (P = .38). PMRT was not associated with a CSS benefit in any subgroup, a finding that persisted in multivariate analyses. Women who received PMRT had an increased 10-year OS rate (70.7% vs 58.4%; P < .001) that was confined to women aged >50 years in a subgroup analysis. This retrospective, population-based analysis demonstrated no increase in CSS with PMRT for women with T3N0 breast cancer, lending further support to the hypothesis that T3N0 disease postmastectomy represents a favorable subset of locally advanced breast cancer. The increased OS associated with PMRT in the absence of improved CSS likely reflects patient selection in this nonrandomized dataset. Prospective evaluation of PMRT

  5. ECO2N V2.0

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Pan, Lehua; Spycher, Nicolas; Doughty, Christine

    2015-02-01

    ECO2N V2.0 is a fluid property module for the TOUGH2 simulator (Version 2.1) that was designed for applications to geologic sequestration of CO2 in saline aquifers and enhanced geothermal reservoirs. ECO2N V2.0 is an enhanced version of the previous ECO2N V1.0 module (Pruess, 2005). It expands the temperature range up to about 300oC whereas V1.0 can only be used for temperatures below about 110oC. V2.0 includes a comprehensive description of the thermodynamic and thermophysical properties of H2O - NaCl - CO2 mixtures, that reproduces fluid properties largely within experimental error for the temperature, pressure and salinity conditions 10 °C T < 300 °C, P < 600 bar, and salinity up to halite saturation. This includes density, viscosity, and specific enthalpy of fluid phases as functions of temperature, pressure, and composition, as well as partitioning of mass components H2O, NaCl and CO2 among the different phases. In particular, V2.0 accounts for the effects of water on the thermophysical properties of the CO2-rich phase, which was ignored in V1.0, using a model consistent with the solubility models developed by Spycher and Pruess (2005, 2010). In terms of solubility models, V2.0 uses the same model for partitioning of mass components among the different phases (Spycher and Pruess, 2005) as V1.0 for the low temperature range (<99oC) but uses a new model (Spycher and Pruess, 2010) for the high temperature range (>109oC). In the transition range (99-109oC), a smooth interpolation is applied to estimate the partitioning as a function of the temperature. Flow processes can be modeled isothermally or non-isothermally, and phase conditions represented may include a single (aqueous or CO2-rich) phase, as well as two-phase (brine-CO2) mixtures. Fluid phases may appear or disappear in the course of a simulation, and solid salt may precipitate or dissolve. Note that the model cannot be applied to subcritical conditions that involves both liquid and gaseous CO2

  6. Ratio between maximum standardized uptake value of N1 lymph nodes and tumor predicts N2 disease in patients with non-small cell lung cancer in 18F-FDG PET-CT scan.

    PubMed

    Honguero Martínez, A F; García Jiménez, M D; García Vicente, A; López-Torres Hidalgo, J; Colon, M J; van Gómez López, O; Soriano Castrejón, Á M; León Atance, P

    2016-01-01

    F-18 fluorodeoxyglucose integrated PET-CT scan is commonly used in the work-up of lung cancer to improve preoperative disease stage. The aim of the study was to analyze the ratio between SUVmax of N1 lymph nodes and primary lung cancer to establish prediction of mediastinal disease (N2) in patients operated on non-small cell lung cancer. This is a retrospective study of a prospective database. Patients operated on non-small cell lung cancer (NSCLC) with N1 disease by PET-CT scan were included. None of them had previous induction treatment, but they underwent standard surgical resection plus systematic lymphadenectomy. There were 51 patients with FDG-PET-CT scan N1 disease. 44 (86.3%) patients were male with a mean age of 64.1±10.8 years. Type of resection: pneumonectomy=4 (7.9%), lobectomy/bilobectomy=44 (86.2%), segmentectomy=3 (5.9%). adenocarcinoma=26 (51.0%), squamous=23 (45.1%), adenosquamous=2 (3.9%). Lymph nodes after surgical resection: N0=21 (41.2%), N1=12 (23.5%), N2=18 (35.3%). Mean ratio of the SUVmax of N1 lymph node to the SUVmax of the primary lung tumor (SUVmax N1/T ratio) was 0.60 (range 0.08-2.80). ROC curve analysis to obtain the optimal cut-off value of SUVmax N1/T ratio to predict N2 disease was performed. At multivariate analysis, we found that a ratio of 0.46 or greater was an independent predictor factor of N2 mediastinal lymph node metastases with a sensitivity and specificity of 77.8% and 69.7%, respectively. SUVmax N1/T ratio in NSCLC patients correlates with mediastinal lymph node metastasis (N2 disease) after surgical resection. When SUVmax N1/T ratio on integrated PET-CT scan is equal or superior to 0.46, special attention should be paid on higher probability of N2 disease. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

  7. The effect of CHEK2 variant I157T on cancer susceptibility: evidence from a meta-analysis.

    PubMed

    Han, Fei-fei; Guo, Chang-long; Liu, Li-hong

    2013-06-01

    Cell cycle checkpoint kinase 2 (CHEK2) is a checkpoint kinase that plays an important role in the DNA damage signaling network. Numerous epidemiological studies have evaluated the association between the CHEK2 I157T variant and cancer susceptibility. However, the results of these studies on the association remain conflicting. The main purpose of this study was to integrate previous results and explore whether the CHEK2 I157T variant is associated with cancer susceptibility. PubMed, Embase (before 2012-10-1), Google Scholar, and CBMdisc were searched for studies on the relationship of the CHEK2 I157T variant and the incidence of cancer. Eligible articles were included for data extraction. The main outcome was the frequency of CHEK2 I157T polymorphisms between cases and controls. Comparison of the distribution of SNP was mainly performed using Review Manager 5.0. The odds ratio (OR) and its 95% confidence interval (95% CI) were used to assess the strength of association. In total, 26,336 cases and 44,219 controls from 18 case-control studies were used in this meta-analysis, and significant associations of the CHEK2 I157T variant with cancer susceptibility were found (OR, 1.39; 95% CI, 1.19-1.63; p<0.0001), breast cancer (OR=1.58, 95% CI=1.42-1.75, p<0.00001) and colorectal cancer (OR=1.67, 95% CI=1.24-2.26, p=0.0008). We also found an association of the CHEK2 I157T variant with familial cases (OR=1.85, 95% CI=1.51-2.26, p<0.00001). However, the association was not established for other types of cancer (OR=1.09, 95% CI=0.75-1.57, p=0.66). This meta-analysis demonstrates that the CHEK2 I157T variant was an important cancer gene, which increases cancer risk, especially in breast and colorectal cancer in Caucasian, and the bioinformatic analysis showed this change was mainly attributed to the decreased hydrophobicity of CHEK2 157T.

  8. [Prognostic value of three different staging schemes based on pN, MLR and LODDS in patients with T3 esophageal cancer].

    PubMed

    Wang, L; Cai, L; Chen, Q; Jiang, Y H

    2017-10-23

    Objective: To evaluate the prognostic value of three different staging schemes based on positive lymph nodes (pN), metastatic lymph nodes ratio (MLR) and log odds of positive lymph nodes (LODDS) in patients with T3 esophageal cancer. Methods: From 2007 to 2014, clinicopathological characteristics of 905 patients who were pathologically diagnosed as T3 esophageal cancer and underwent radical esophagectomy in Zhejiang Cancer Hospital were retrospectively analyzed. Kaplan-Meier curves and Multivariate Cox proportional hazards models were used to evaluate the independent prognostic factors. The values of three lymph node staging schemes for predicting 5-year survival were analyzed by using receiver operating characteristic (ROC) curves. Results: The 1-, 3- and 5-year overall survival rates of patients with T3 esophageal cancer were 80.9%, 50.0% and 38.4%, respectively. Multivariate analysis showed that MLR stage, LODDS stage and differentiation were independent prognostic survival factors ( P <0.05 for all). ROC curves showed that the area under the curve of pN stage, MLR stage, LODDS stage was 0.607, 0.613 and 0.618, respectively. However, the differences were not statistically significant ( P >0.05). Conclusions: LODDS is an independent prognostic factor for patients with T3 esophageal cancer. The value of LODDS staging system may be superior to pN staging system for evaluating the prognosis of these patients.

  9. Management of Posterior Glottic Stenosis using the Combined Glottic Reconstruction Procedure.

    PubMed

    Nouraei, S A R; Dorman, E B; Vokes, D E

    2018-05-29

    Laryngotracheal stenosis secondary to Bilateral Vocal Fold Mobility Impairment (BVFMI) is a challenging condition to treat. The glottic aperture accounts for 25% of the respiratory resistance 1 and BVFMI prevents its breath-by-breath regulation, causing severe airway compromise. Moreover, since the larynx is also the organ of phonation and its reflexive closure during swallowing is the principal airway protective mechanism, improving airway may worsen dysphonia, dysphagia, and aspiration. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  10. Study design and early result of a phase I study of SABR for early-stage glottic cancer.

    PubMed

    Yu, Tosol; Wee, Chan Woo; Choi, Noorie; Wu, Hong-Gyun; Kang, Hyun-Cheol; Park, Jong Min; Kim, Jung-In; Kim, Jin Ho; Kwon, Tack-Kyun; Chung, Eun-Jae

    2018-05-14

    Avoidance of organs at risk has become possible with advances in image-guided volumetric-modulated arc therapy (VMAT) techniques. This study was designed to evaluate the safety and feasibility of stereotactic ablative radiotherapy (SABR) for early stage glottic cancer. This report presents the preliminary result of the first and second dose level. Fraction size was increased from 3.5 gray (Gy) (total dose 59.5 Gy) to 9 Gy (total dose 45 Gy). Dose-limiting toxicities were defined as grade 3 or higher treatment-related toxicities. Voice outcome was assessed with electroglottography, and quality of life (QoL) was measured with the Head and Neck Cancer Inventory (HNCI). Seven patients received 59.5 Gy at 3.5 Gy per fraction as the first dose level, and five patients received 55 Gy at 5 Gy per fraction as the second dose level. None of the patients developed grade 3+ toxicity throughout a median follow-up of 17.5 months (range, 1.7-30.6 months). One patient in the second dose level recurred in the primary site at 4 months after radiotherapy (RT) and received total laryngectomy. The rest of participants were disease-free at locoregional and distant sites. Jitter, shimmer, mean phonation time, and noise-to-harmony ratio did not change significantly at 6 months after RT. HNCI scores between pretreatment and posttreatment were not significantly different (P = 0.221). This study revealed acceptable toxicity, voice outcome, and QoL in patients treated with hypofractionated VMAT of 3.5 Gy and 5 Gy per fraction. This phase I study is currently ongoing with a dose of 55 Gy in 11 fractions and 45 Gy in five fractions. 2b. Laryngoscope, 2018. © 2018 The American Laryngological, Rhinological and Otological Society, Inc.

  11. Study of the Histopathologic Characteristics and Surface Morphologies of Glottic Carcinomas With Anterior Vocal Commissure Involvement

    PubMed Central

    Wu, Jianhui; Zhao, Jing; Wang, Zhangfeng; Li, Zenghong; Luo, Jie; Liao, Bing; Yang, Zhiyun; Liu, Qihong; Wang, Bin; Wen, Weiping; Lei, Wenbin

    2015-01-01

    Abstract This article explores the features and the role of the anterior vocal commissure (AVC) structure and the surface morphologies of glottic carcinomas with AVC involvement to provide a reference for the selection of transoral carbon dioxide (CO2) laser surgery. A total of 31 cases of glottic carcinomas with AVC involvement from May 2012 to January 2014 were included. All patients underwent electronic laryngoscopic examinations and computed tomography scans to determine the surface morphology. After surgery, the tumor specimens were resected integrally, and axial serial sections parallel to the plane of vocal cords were taken to explore the features and possible invasion paths of the glottic carcinomas with AVC involvement. The rates of involvement of the supraglottis and subglottis were 71.4% and 14.8%, respectively, via the AVC. The involvement of the superficial layer of the unilateral or bilateral vocal cords without involvement of the vocal muscle in the AVC region (IVM) or the cartilage was present in 15 cases (48.4%). The involvement of the superficial layer of the unilateral and bilateral vocal cords occurred in 16 cases (51.6%) with the IVM in 13 cases and the involvement of the intermediate lamina of the thyroid cartilage (ITC) in 8 cases. The involvement of the ITC was associated with the involvement of the vocal muscle of the AVC region (P < 0.05). Among the pushing carcinomas, 15 of 21 (71.4%) presented with well-defined tumor mass, and 8 of 10 (80.0%) infiltrating carcinomas presented with multiple tumor nests that were often surrounded by fibrosis (P < 0.05). The AVC is an important path of invasion of subglottic in glottic carcinomas but less so for suparglottic. The Broyles’ ligaments acted as a barrier against the spread of the tumors to the thyroid cartilage, but this role was obviously weaken by the involvement of the vocal muscle of the AVC region. The infiltrating carcinomas presented with multiple tumor nests in fibrous tissue

  12. Crystal structure and optical property of complex perovskite oxynitrides ALi0.2Nb0.8O2.8N0.2, ANa0.2Nb0.8O2.8N0.2, and AMg0.2Nb0.8O2.6N0.4 (A = Sr, Ba)

    NASA Astrophysics Data System (ADS)

    Moon, Keon Ho; Avdeev, Maxim; Kim, Young-Il

    2017-10-01

    Oxynitride type complex perovskites AM0.2Nb0.8O3-xNx (A = Sr, Ba; M = Li, Na, Mg) were newly synthesized by the solid state diffusion of Li+, Na+, or Mg2+ into the layered oxide, A5Nb4O15, with concurrent O/N substitution. Neutron and synchrotron X-ray Rietveld refinement showed that SrLi0.2Nb0.8O2.8N0.2, SrNa0.2Nb0.8O2.8N0.2, and SrMg0.2Nb0.8O2.6N0.4 had body-centered tetragonal symmetry (I4/mcm), while those with A = Ba had simple cubic symmetry (Pm 3 ̅ m). In the tetragonal Sr-compounds, the nitrogen atoms were localized on the c-axial 4a site. However, the octahedral cations, M/Nb (M = Li, Na, Mg) were distributed randomly in all six compounds. The lattice volume of AM0.2Nb0.8O3-xNx was dependent on various factors including the type of A and the electronegativity of M. Compared to the simple perovskites, ANbO2N (A = Sr, Ba), AM0.2Nb0.8O3-xNx had wider band gaps (1.76-2.15 eV for A = Sr and 1.65-2.10 eV for A = Ba), but significantly lower sub-gap absorption.

  13. Type 2 Diabetes and Risk of Incident Cancers in China: A Prospective Study among 0.5 Million Chinese Adults.

    PubMed

    Pan, Xiong-Fei; He, Meian; Yu, Canqing; Lv, Jun; Guo, Yu; Bian, Zheng; Yang, Ling; Chen, Yiping; Wu, Tangchun; Chen, Zhengming; Pan, An; Li, Liming

    2018-01-03

    Using data from the China Kadoorie Biobank study, we conducted a prospective investigation on the association between type 2 diabetes mellitus (T2DM) and cancer risk in Chinese adults. A total of 508,892 participants (mean (standard deviation) age = 51.5 (10.7) years) without prior cancer diagnosis at baseline (2004-2008) were included. We documented 17,463 incident cancer cases during follow-up until December 31, 2013. Participants with T2DM had increased risks of total and certain site-specific cancers, and the hazard ratio (HR) was 1.13 (95% confidence interval (CI): 1.07, 1.19) for total cancer, 1.51 (1.29, 1.76) for liver cancer, 1.86 (1.43, 2.41) for pancreatic cancer, and 1.21 (1.01, 1.47) for female breast cancer. The associations were largely consistent when doctor-diagnosed and screen-detected T2DM were analyzed separately, except for colorectal cancer (HR = 0.91 (95% CI: 0.73, 1.13) for doctor-diagnosed T2DM, and HR = 1.44 (95% CI: 1.18, 1.77) for screen-detected T2DM). In participants without prior diagnosis of T2DM, higher random blood glucose levels were positively associated with risk of total cancer, liver cancer, and female breast cancer (all P for trend ≤0.02). In conclusion, T2DM is associated with an increased risk of new-onset cancer in China, particularly cancers of the liver, pancreas, and female breast. © The Author(s) 2018. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. Incidence, Risk Factors, and Analysis of Survival of Unexpected N2 Disease in Stage I Non-Small Cell Lung Cancer.

    PubMed

    Fiorelli, Alfonso; Sagan, Dariusz; Mackiewicz, Lukasz; Cagini, Lucio; Scarnecchia, Elisa; Chiodini, Paolo; Caronia, Francesco Paolo; Puma, Francesco; Santini, Mario; Ragusa, Mark

    2015-10-01

    To evaluate the incidence, predictors, and survival of unexpected pN2 disease in patients with clinical stage I non-small cell lung cancer. This is a retrospective observational multicenter study on all consecutive patients operated for clinical stage I non-small cell lung cancer from January 2006 to December 2012. Medical records were reviewed to investigate the incidence and risk factors for unexpected pN2 disease. Then, the survival of patients with unexpected pN2 disease was statistically compared with that of patients with clinical N2 disease operated after induction therapy in the same period. Our study population counted 901 patients. An incidence of 12% (108/901) unexpected pN2 disease was found. Among 3,389 lymph nodes sampled, 124 distinct metastases were found. Of the 108 patients, 92 (85%) had metastases in single N2 station and 16 (15%) patients had disease in multiple N2 stations; 47 (44%) had pN2 disease without pN1 involvement (skip metastases) and 61/108 (56%) had also pN1 metastases. Factors associated with unexpected pN2 disease were central tumor location (p < 0.003), cT2a (p < 0.0001) and pT2a stage (p < 0.0001), pN1 disease (p = 0.004), and a standard uptake value > 4.0 (0.007). Patients with pN2 disease compared with patients with cN2 disease presented a better median overall survival (56 versus 20 months; p = 0.001) and disease-free survival (46 versus 11 months; p < 0.0001). The preoperative effort to discover unexpected pN2 disease in patients with clinical stage I non-small cell lung cancer is not justified, considering their good survival. Thus, preoperative invasive mediastinal procedures in such cases are not indicated. Georg Thieme Verlag KG Stuttgart · New York.

  15. Prospective Trial of Stereotactic Body Radiation Therapy for Both Operable and Inoperable T1N0M0 Non-Small Cell Lung Cancer: Japan Clinical Oncology Group Study JCOG0403

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Nagata, Yasushi, E-mail: nagat@hiroshima-u.ac.jp; Hiraoka, Masahiro; Shibata, Taro

    2015-12-01

    Purpose: To evaluate, in Japan Clinical Oncology Group study 0403, the safety and efficacy of stereotactic body radiation therapy (SBRT) in patients with T1N0M0 non-small cell lung cancer (NSCLC). Methods and Materials: Eligibility criteria included histologically or cytologically proven NSCLC, clinical T1N0M0. Prescribed dose was 48 Gy at the isocenter in 4 fractions. The primary endpoint was the percent (%) 3-year overall survival. The threshold % 3-year survival to be rejected was set at 35% for inoperable patients, whereas the expected % 3-year survival was 80% for operable patients. Results: Between July 2004 and November 2008, 169 patients from 15 institutionsmore » were registered. One hundred inoperable and 64 operable patients (total 164) were eligible. Patients' characteristics were 122 male, 47 female; median age 78 years (range, 50-91 years); adenocarcinomas, 90; squamous cell carcinomas, 61; others, 18. Of the 100 inoperable patients, the % 3-year OS was 59.9% (95% confidence interval 49.6%-68.8%). Grade 3 and 4 toxicities were observed in 10 and 2 patients, respectively. No grade 5 toxicity was observed. Of the 64 operable patients, the % 3-year OS was 76.5% (95% confidence interval 64.0%-85.1%). Grade 3 toxicities were observed in 5 patients. No grade 4 and 5 toxicities were observed. Conclusions: Stereotactic body radiation therapy for stage I NSCLC is effective, with low incidences of severe toxicity. This treatment can be considered a standard treatment for inoperable stage I NSCLC. This treatment is promising as an alternative to surgery for operable stage I NSCLC.« less

  16. T2-weighted MRI-derived textural features reflect prostate cancer aggressiveness: preliminary results.

    PubMed

    Nketiah, Gabriel; Elschot, Mattijs; Kim, Eugene; Teruel, Jose R; Scheenen, Tom W; Bathen, Tone F; Selnæs, Kirsten M

    2017-07-01

    To evaluate the diagnostic relevance of T2-weighted (T2W) MRI-derived textural features relative to quantitative physiological parameters derived from diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) MRI in Gleason score (GS) 3+4 and 4+3 prostate cancers. 3T multiparametric-MRI was performed on 23 prostate cancer patients prior to prostatectomy. Textural features [angular second moment (ASM), contrast, correlation, entropy], apparent diffusion coefficient (ADC), and DCE pharmacokinetic parameters (K trans and V e ) were calculated from index tumours delineated on the T2W, DW, and DCE images, respectively. The association between the textural features and prostatectomy GS and the MRI-derived parameters, and the utility of the parameters in differentiating between GS 3+4 and 4+3 prostate cancers were assessed statistically. ASM and entropy correlated significantly (p < 0.05) with both GS and median ADC. Contrast correlated moderately with median ADC. The textural features correlated insignificantly with K trans and V e . GS 4+3 cancers had significantly lower ASM and higher entropy than 3+4 cancers, but insignificant differences in median ADC, K trans , and V e . The combined texture-MRI parameters yielded higher classification accuracy (91%) than the individual parameter sets. T2W MRI-derived textural features could serve as potential diagnostic markers, sensitive to the pathological differences in prostate cancers. • T2W MRI-derived textural features correlate significantly with Gleason score and ADC. • T2W MRI-derived textural features differentiate Gleason score 3+4 from 4+3 cancers. • T2W image textural features could augment tumour characterization.

  17. Communication changes following non-glottic head and neck cancer management: The perspectives of survivors and carers.

    PubMed

    Nund, Rebecca L; Rumbach, Anna F; Debattista, Bridget C; Goodrow, Martha N T; Johnson, Kori A; Tupling, Laura N; Scarinci, Nerina A; Cartmill, Bena; Ward, Elizabeth C; Porceddu, Sandro V

    2015-06-01

    Head and neck cancer (HNC) survivors may experience functional changes to their voice, speech and hearing following curative chemoradiotherapy. However, few studies have explored the impact of living with such changes from the perspective of the HNC survivor and their carer. The current study employed a person-centred approach to explore the lived experience of communication changes following chemoradiotherapy treatment for HNC from the perspective of survivors and carers. Participants included 14 survivors with non-glottic HNC and nine carers. All participants took part in in-depth interviews where they were encouraged to describe their experiences of living with and adjusting to communication changes following treatment. Interviews were analysed as a single data set. Four themes emerged including: (1) impairments in communication sub-systems; (2) the challenges of communicating in everyday life; (3) broad ranging effects of communication changes; and (4) adaptations as a result of communication changes. These data confirm that communication changes following chemoradiotherapy have potentially negative psychosocial impacts on both the HNC survivor and their carer. Clinicians should consider the impact of communication changes on the life of the HNC survivor and their carer and provide adequate and timely education and management to address the needs of this population.

  18. tRF2Cancer: A web server to detect tRNA-derived small RNA fragments (tRFs) and their expression in multiple cancers.

    PubMed

    Zheng, Ling-Ling; Xu, Wei-Lin; Liu, Shun; Sun, Wen-Ju; Li, Jun-Hao; Wu, Jie; Yang, Jian-Hua; Qu, Liang-Hu

    2016-07-08

    tRNA-derived small RNA fragments (tRFs) are one class of small non-coding RNAs derived from transfer RNAs (tRNAs). tRFs play important roles in cellular processes and are involved in multiple cancers. High-throughput small RNA (sRNA) sequencing experiments can detect all the cellular expressed sRNAs, including tRFs. However, distinguishing genuine tRFs from RNA fragments generated by random degradation remains a major challenge. In this study, we developed an integrated web-based computing system, tRF2Cancer, to accurately identify tRFs from sRNA deep-sequencing data and evaluate their expression in multiple cancers. The binomial test was introduced to evaluate whether reads from a small RNA-seq data set represent tRFs or degraded fragments. A classification method was then used to annotate the types of tRFs based on their sites of origin in pre-tRNA or mature tRNA. We applied the pipeline to analyze 10 991 data sets from 32 types of cancers and identified thousands of expressed tRFs. A tool called 'tRFinCancer' was developed to facilitate the users to inspect the expression of tRFs across different types of cancers. Another tool called 'tRFBrowser' shows both the sites of origin and the distribution of chemical modification sites in tRFs on their source tRNA. The tRF2Cancer web server is available at http://rna.sysu.edu.cn/tRFfinder/. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  19. Estrogen receptor (α and β) but not androgen receptor expression is correlated with recurrence, progression and survival in post prostatectomy T3N0M0 locally advanced prostate cancer in an urban Greek population

    PubMed Central

    Megas, Georgios; Chrisofos, Michael; Anastasiou, Ioannis; Tsitlidou, Aida; Choreftaki, Theodosia; Deliveliotis, Charalampos

    2015-01-01

    The objective of this study was to evaluate the expression of estrogen receptors (ER(α) and ER(β)) and androgen receptors (ARs) as prognostic factors for biochemical recurrence, disease progression and survival in patients with pT3N0M0 prostate cancer (PCa) in an urban Greek population. A total of 100 consecutive patients with pT3N0M0 PCa treated with radical prostatectomy participated in the study. The mean age and follow-up were 64.2 and 6 years, respectively. The HSCORE was used for semi-quantitative analysis of the immunoreactivity of the receptors. The prognostic value of the ER(α) and ER(β) and AR was assessed in terms of recurrence, progression, and survival. AR expression was not associated with any of the above parameters; however, both ERs correlated with the prognosis. A univariate Cox regression analysis showed that ER(α) positive staining was significantly associated with a greater hazard for all outcomes. Increased ER(β) staining was significantly associated with a lower hazard for all outcomes in the univariate analysis. When both ER HSCORES were used for the analysis, it was found that patients with high ER(α) or low ER(β) HSCORES compared with patients with negatively stained ER(α) and >1.7 hSCORE ER(β) had 6.03, 10.93, and 10.53 times greater hazard for biochemical disease recurrence, progression of disease and death, respectively. Multiple Cox proportional hazard analyses showed that the age, preoperative prostate specific antigen, Gleason score and ERs were independent predictors of all outcomes. ER expression is an important prognosticator after radical prostatectomy in patients with pT3N0M0 PCa. By contrast, AR expression has limited prognostic value. PMID:25219910

  20. Estrogen receptor (α and β) but not androgen receptor expression is correlated with recurrence, progression and survival in post prostatectomy T3N0M0 locally advanced prostate cancer in an urban Greek population.

    PubMed

    Megas, Georgios; Chrisofos, Michael; Anastasiou, Ioannis; Tsitlidou, Aida; Choreftaki, Theodosia; Deliveliotis, Charalampos

    2015-01-01

    The objective of this study was to evaluate the expression of estrogen receptors (ER(α) and ER(β)) and androgen receptors (ARs) as prognostic factors for biochemical recurrence, disease progression and survival in patients with pT3N0M0 prostate cancer (PCa) in an urban Greek population. A total of 100 consecutive patients with pT3N0M0 PCa treated with radical prostatectomy participated in the study. The mean age and follow-up were 64.2 and 6 years, respectively. The HSCORE was used for semi-quantitative analysis of the immunoreactivity of the receptors. The prognostic value of the ER(α) and ER(β) and AR was assessed in terms of recurrence, progression, and survival. AR expression was not associated with any of the above parameters; however, both ERs correlated with the prognosis. A univariate Cox regression analysis showed that ER(α) positive staining was significantly associated with a greater hazard for all outcomes. Increased ER(β) staining was significantly associated with a lower hazard for all outcomes in the univariate analysis. When both ER HSCORES were used for the analysis, it was found that patients with high ER(α) or low ER(β) HSCORES compared with patients with negatively stained ER(α) and >1.7 hSCORE ER(β) had 6.03, 10.93, and 10.53 times greater hazard for biochemical disease recurrence, progression of disease and death, respectively. Multiple Cox proportional hazard analyses showed that the age, preoperative prostate specific antigen, Gleason score and ERs were independent predictors of all outcomes. ER expression is an important prognosticator after radical prostatectomy in patients with pT3N0M0 PCa. By contrast, AR expression has limited prognostic value.

  1. Occult Nodal Disease Prevalence and Distribution in Recurrent Laryngeal Cancer Requiring Salvage Laryngectomy.

    PubMed

    Birkeland, Andrew C; Rosko, Andrew J; Issa, Mohamad R; Shuman, Andrew G; Prince, Mark E; Wolf, Gregory T; Bradford, Carol R; McHugh, Jonathan B; Brenner, J Chad; Spector, Matthew E

    2016-03-01

    The indications for neck dissection concurrent with salvage laryngectomy in the clinically N0 setting remain unclear. Our goals were to determine the prevalence of occult nodal disease, analyze nodal disease distribution patterns, and identify predictors of occult nodal disease in a salvage laryngectomy cohort. Case series with planned data collection. Tertiary academic center. Patients with persistent or recurrent laryngeal squamous cell carcinoma (LSCC) after radiation/chemoradiation failure undergoing salvage laryngectomy with neck dissection. We analyzed a single-institution retrospective case series of patients between 1997 and 2014 and identified those who had clinically N0 (cN0) necks (n = 203). Clinical and pathologic data, including nodal prevalence and distribution, were collected and statistical analyses performed. Overall, cN0 necks had histologically positive occult nodes in 17% (n = 35) of cases. Univariate predictors of occult nodal positivity included recurrent T4 stage (34% T4 vs 12% non-T4; P = .0003) and supraglottic subsite (28% supraglottic vs 10% nonsupraglottic; P = .0006). Histologically positive nodes associated with supraglottic primaries were most frequently positive in ipsilateral levels II and III (17% and 16%). Positive nodes for glottic LSCC were most frequently positive in the ipsilateral and contralateral paratracheal nodes (11% and 9%). Histologically positive occult nodes are identified in 17% of cN0 patients undergoing salvage laryngectomy with neck dissection. Occult nodal disease varies in frequency and distribution based on tumor subsite. Predictors of high (>20%) occult nodal positivity include T4 tumors and supraglottic subsite. In glottic LSCC, the most frequent sites of occult nodal disease are the paratracheal nodal basins. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

  2. Outcomes after radical prostatectomy for patients with clinical stages T1-T2 prostate cancer with pathologically positive lymph nodes in the prostate-specific antigen era.

    PubMed

    Dorin, Ryan P; Lieskovsky, Gary; Fairey, Adrian S; Cai, Jie; Daneshmand, Siamak

    2013-11-01

    To evaluate the outcomes of radical prostatectomy (RP) and pelvic lymph node dissection (PLND) for clinically organ confined prostate cancer (CaP) with regional lymph node metastases (pN1) treated in the era of prostate-specific antigen (PSA) screening. A single institution cohort of 2,487 men with cT1-T2 CaP treated with open radical prostatectomy and pelvic lymph node dissection between 1988 and 2008 were analyzed. Kaplan-Meier and Cox proportional regression models were used to analyze overall survival (OS), clinical recurrence-free survival (cRFS), and biochemical recurrence-free survival (bRFS). Overall, 150 out of 2,487 patients (6%) had pN1 disease, with a median follow-up of 10.4 years. The predicted 10-year OS, cRFS, and bRFS rates for patients with pN0 and pN1 were 86% and 74% (Log rank P < 0.001), 97% and 84% (Log rank P < 0.001), and 88% and 57% (Log rank P < 0.001), respectively. In the subset of pN1 patients treated with surgery only (n = 49), the predicted 10-year OS, cRFS, and bRFS rates were 81%, 80%, and 59%, respectively. Exploratory univariate regression analysis showed that age (P = 0.003), total number of lymph nodes identified (P = 0.040), and total number of positive lymph nodes identified (P = 0.004) were associated with OS. Total number of positive lymph nodes (LNs) identified was also significantly associated with cRFS (P = 0.05). The incidence of pN1 in patients with cT1-T2 CaP treated with surgery in the era of PSA screening was low. RP and PLND demonstrated therapeutic efficacy in a subset of pN1 patients treated with surgery alone. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Role of adjuvant chemoradiotherapy in T4N0 stage IV head and neck cancer: A National Cancer Database analysis.

    PubMed

    Kirke, Diana N; Qureshi, Muhammad M; Kamran, Sophia C; Ezzat, Waleed; Jalisi, Scharukh; Salama, Andrew; Everett, Peter C; Truong, Minh Tam

    2018-06-01

    The purpose of this study was to evaluate the role of postoperative adjuvant radiotherapy (surgery + adjuvant RT) versus adjuvant chemoradiotherapy (surgery + adjuvant CRT) in patients with T4N0M0, stage IV head and neck squamous cell carcinoma (HNSCC). Between 1998 and 2011, 3518 and 885 patients were treated with surgery + adjuvant RT and surgery + adjuvant CRT, respectively. Three-year overall survival (OS) rates were determined and crude and adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were computed. Median follow-up was 41.8 months with 2193 reported deaths. The 3-year OS was 67.5% for surgery + adjuvant RT and 70.5% for surgery + adjuvant CRT (P = .013). For negative margins, the corresponding 3-year OS was 70.1% and 74.9% (P = .005). For positive margins, the corresponding 3-year OS was 56.0% and 60.6% (P = .079). On multivariate analysis, the beneficial effect for adjuvant CRT over adjuvant RT was not significant (HR 0.90; CI 0.79-1.03; P = .124). In this cohort of patients with T4N0 HNSCC treated with surgery, there was no observed survival benefit of adjuvant CRT over adjuvant RT on multivariate analysis. © 2018 Wiley Periodicals, Inc.

  4. Voice quality after endoscopic laser surgery and radiotherapy for early glottic cancer: objective measurements emphasizing the Voice Handicap Index

    PubMed Central

    Caminero Cueva, Maria Jesús; Señaris González, Blanca; Llorente Pendás, José Luis; Gorriz Gil, Carmen; López Llames, Aurora; Alonso Pantiga, Ramón; Suárez Nieto, Carlos

    2007-01-01

    We analyzed the functional outcome and self-evaluation of the voice of patients with T1 glottic carcinoma treated with endoscopic laser surgery and radiotherapy. We performed an objective voice evaluation, as well as a physical, emotional and functional well being assessment of 19 patients treated with laser surgery and 18 patients treated with radiotherapy. Voice quality is affected both by surgery and radiotherapy. Voice parameters only show differences in the maximum phonation time between both treatments. Results in the Voice Handicap Index show that radiotherapy has less effect on patient voice quality perception. There is a reduced impact on the patient’s perception of voice quality after radiotherapy, despite there being no significant differences in vocal quality between radiotherapy and laser cordectomy. PMID:17999074

  5. Phase I/II study of hypofractioned radiation with three-dimensional conformal radiotherapy for clinical T3-4N0-1M0 stage esophageal carcinoma.

    PubMed

    Song, Y-P; Ma, J-B; Hu, L-K; Zhou, W; Chen, E-C; Zhang, W

    2011-02-01

    Compared to conventional fractionated-dose radiotherapy, high hypofractionated-dose radiotherapy could yield tumoricidal effects. However, few clinical trials of hypofractionated radiotherapy in loco-regionally advanced incurable esophageal cancer at present have yet been performed. The purpose of the current study was to evaluate the efficacy and toxicity of hypofractioned radiation with three-dimensional conformal radiotherapy for clinical T3-4N0-1M0 stage esophageal carcinoma. From September 2003 to December 2005, 45 patients with locally advanced esophageal carcinoma were grouped and received three-dimensional conformal hypofractioned radiotherapy (3D-CRT) whose fractionated dose was gradually increase per group. Radiotherapy was administered to a total dose of from 50 to 54 Gy (fractionated dose of from 3.0 to 6.0 Gy, 3 times weekly), over a 3-4 week period. And patients received 4 cycles chemotherapy. The median follow-up period for survivors was 38 months. Treatment tolerance rate was 78.8% with daily dose of from 3 to 5 Gy. There are 21.2% patients occurring Grade ≥ 3 acute toxicities. But patients couldn't tolerate daily dose of 6 Gy (55.6%). The 1-year, 2-year and 3-year local control rates were 62%, 49% and 39% respectively. And the 1-year, 2-year and 3-year overall survival rates were 34%, 21% and 9% respectively. The median overall survival time was 17 months. At the time of following up, 13 patients (31.0%) had occurred esophageal late complications, with mainly esophageal perforation, hemorrhage or stenosis, including initial stenosis aggravation. Therefore hypofractionated irradiation was thought to be feasible for clinical T3-4N0-1M0 stage esophageal carcinoma. And daily dose of ≤5 Gy was comparatively suitable in hypofractionated irradiation for esophageal carcinoma, and the patients tolerated well. But further research was in need also.

  6. FUNCTIONAL CHARACTERIZATION OF THE A411T (L137F) and G364A (D122N) GENETIC POLYMORPHISMS IN HUMAN N-ACETYLTRANSFERASE 2

    PubMed Central

    Zang, Yu; Zhao, Shuang; Doll, Mark A.; States, J Christopher; Hein, David W.

    2007-01-01

    Human N-acetyltransferase 2 (NAT2) genetic polymorphisms may modify drug efficacy and toxicity and individual cancer susceptibility from carcinogen exposure. A411T (L137F) and G364A (D122N) are two single nucleotide polymorphisms (SNPs) that coexist with other SNPs in human NAT2 alleles NAT2*5I and NAT2*12D, respectively. Cloning and expression in COS-1 cells showed that both A411T and G364A reduced NAT2 immunoreactive protein to an undetectable level without causing changes in mRNA level. Missense mutants displayed different effects on sulfamethazine N-acetylation activity for both L137 (wild-type: 70.2±5.2; L137F: 1.34±0.03; L137W: non-detectable; L137I: 34.2±2.0; L137G: 0.52±0.04 nmol/min/mg) and D122 (wildtype: 70.2±5.2; D122R: non-detectable; D122Q: non-detectable; D122E: 1.72±0.24 nmol/min/mg). To further test our hypothesis that A411T (L137F) and G364A (D122N) accelerate protein degradation, various NAT2 alleles were cloned and expressed in E. coli, which does not possess the ubiquitin-mediated degradation pathway. In contrast to the expression in mammalian cells, recombinant NAT2 possessing either of these two SNPs showed no reduction in immunoreactive NAT2 level when expressed in E. coli. These findings suggest that both A411T (L137F) and G364A (D122N) enhance NAT2 degradation, resulting in reduced NAT2 protein and catalytic activity for NAT2 5I and NAT2 12D. PMID:17264801

  7. Trial Vocal Fold Injection Predicts Thyroplasty Outcomes in Nonparalytic Glottic Incompetence.

    PubMed

    Dumberger, Lukas D; Overton, Lewis; Buckmire, Robert A; Shah, Rupali N

    2017-04-01

    Trial vocal fold injection (TVFI) may be used prior to permanent medialization when voice outcome is uncertain. We aimed to determine whether voice outcomes of TVFI are predictive of, or correlate with outcomes after type I Gore-Tex medialization thyroplasty (GMT) in patients with nonparalytic glottic incompetence (GI). Thirty-five patients with nonparalytic GI who underwent TVFI followed by GMT were retrospectively reviewed. Change in voice-related quality of life (VRQOL) after TVFI was compared to change in VRQOL 3 to 9 months after GMT. Similar comparisons were made for change in glottal function index (GFI) and change in grade, roughness, breathiness, asthenia, and strain (GRBAS). Sample correlation coefficients were calculated. Change in VRQOL after TVFI showed good correlation with change in VRQOL after GMT, r = 0.55. Change in GFI after TVFI showed strong correlation with change in GFI after GMT, r = 0.74. Change in GRBAS after TVFI showed excellent correlation with change in GRBAS after GMT, r = 0.90. The TVFI is a useful tool in nonparalytic GI when outcomes from glottic closure procedures are not clear. Voice outcome measures after TVFI strongly correlate with outcomes from GMT. These data may be used to more confidently counsel patients regarding their predicted outcomes of permanent medialization.

  8. Long-term Impact of Adjuvant Versus Early Salvage Radiation Therapy in pT3N0 Prostate Cancer Patients Treated with Radical Prostatectomy: Results from a Multi-institutional Series.

    PubMed

    Fossati, Nicola; Karnes, R Jeffrey; Boorjian, Stephen A; Moschini, Marco; Morlacco, Alessandro; Bossi, Alberto; Seisen, Thomas; Cozzarini, Cesare; Fiorino, Claudio; Noris Chiorda, Barbara; Gandaglia, Giorgio; Dell'Oglio, Paolo; Joniau, Steven; Tosco, Lorenzo; Shariat, Shahrokh; Goldner, Gregor; Hinkelbein, Wolfgang; Bartkowiak, Detlef; Haustermans, Karin; Tombal, Bertrand; Montorsi, Francesco; Van Poppel, Hein; Wiegel, Thomas; Briganti, Alberto

    2017-06-01

    Three prospective randomised trials reported discordant findings regarding the impact of adjuvant radiation therapy (aRT) versus observation for metastasis-free survival (MFS) and overall survival (OS) among patients with pT3N0 prostate cancer treated with radical prostatectomy (RP). None of these trials systematically included patients who underwent early salvage radiation therapy (esRT). To test the hypothesis that aRT was associated with better cancer control and survival compared with observation followed by esRT. Using a multi-institutional cohort from seven tertiary referral centres, we retrospectively identified 510 pT3pN0 patients with undetectable prostate-specific antigen (PSA) after RP between 1996 and 2009. Patients were stratified into two groups: aRT (group 1) versus observation followed by esRT in case of PSA relapse (group 2). Specifically, esRT was administered at a PSA level ≤0.5ng/ml. We compared aRT versus observation followed by esRT. The evaluated outcomes were MFS and OS. Multivariable Cox regression analyses tested the association between groups (aRT vs observation followed by esRT) and oncologic outcomes. Covariates consisted of pathologic stage (pT3a vs pT3b or higher), pathologic Gleason score (≤6, 7, or ≥8), surgical margin status (negative vs positive), and year of surgery. An interaction with groups and baseline patient risk was tested for the hypothesis that the impact of aRT versus observation followed by esRT was different by pathologic characteristics. The nonparametric curve fitting method was used to explore graphically the relationship between MFS and OS at 8 yr and baseline patient risk (derived from the multivariable analysis). Overall, 243 patients (48%) underwent aRT, and 267 (52%) underwent initial observation. Within the latter group, 141 patients experienced PSA relapse and received esRT. Median follow-up after RP was 94 mo (interquartile range [IQR]: 53-126) and 92 mo (IQR: 70-136), respectively (p=0.2). MFS (92

  9. Urinary bladder cancer T-staging from T2-weighted MR images using an optimal biomarker approach

    NASA Astrophysics Data System (ADS)

    Wang, Chuang; Udupa, Jayaram K.; Tong, Yubing; Chen, Jerry; Venigalla, Sriram; Odhner, Dewey; Guzzo, Thomas J.; Christodouleas, John; Torigian, Drew A.

    2018-02-01

    Magnetic resonance imaging (MRI) is often used in clinical practice to stage patients with bladder cancer to help plan treatment. However, qualitative assessment of MR images is prone to inaccuracies, adversely affecting patient outcomes. In this paper, T2-weighted MR image-based quantitative features were extracted from the bladder wall in 65 patients with bladder cancer to classify them into two primary tumor (T) stage groups: group 1 - T stage < T2, with primary tumor locally confined to the bladder, and group 2 - T stage < T2, with primary tumor locally extending beyond the bladder. The bladder was divided into 8 sectors in the axial plane, where each sector has a corresponding reference standard T stage that is based on expert radiology qualitative MR image review and histopathologic results. The performance of the classification for correct assignment of T stage grouping was then evaluated at both the patient level and the sector level. Each bladder sector was divided into 3 shells (inner, middle, and outer), and 15,834 features including intensity features and texture features from local binary pattern and gray-level co-occurrence matrix were extracted from the 3 shells of each sector. An optimal feature set was selected from all features using an optimal biomarker approach. Nine optimal biomarker features were derived based on texture properties from the middle shell, with an area under the ROC curve of AUC value at the sector and patient level of 0.813 and 0.806, respectively.

  10. MeT-DB V2.0: elucidating context-specific functions of N6-methyl-adenosine methyltranscriptome

    PubMed Central

    Liu, Hui; Wang, Huaizhi; Wei, Zhen; Zhang, Songyao; Hua, Gang; Zhang, Shao-Wu; Zhang, Lin; Gao, Shou-Jiang

    2018-01-01

    Abstract Methyltranscriptome is an exciting new area that studies the mechanisms and functions of methylation in transcripts. A knowledge base with the systematic collection and curation of context specific transcriptome-wide methylations is critical for elucidating their biological functions as well as for developing bioinformatics tools. Since its inception in 2014, the Met-DB (Liu, H., Flores, M.A., Meng, J., Zhang, L., Zhao, X., Rao, M.K., Chen, Y. and Huang, Y. (2015) MeT-DB: a database of transcriptome methylation in mammalian cells. Nucleic Acids Res., 43, D197–D203), has become an important resource for methyltranscriptome, especially in the N6-methyl-adenosine (m6A) research community. Here, we report Met-DB v2.0, the significantly improved second version of Met-DB, which is entirely redesigned to focus more on elucidating context-specific m6A functions. Met-DB v2.0 has a major increase in context-specific m6A peaks and single-base sites predicted from 185 samples for 7 species from 26 independent studies. Moreover, it is also integrated with a new database for targets of m6A readers, erasers and writers and expanded with more collections of functional data. The redesigned Met-DB v2.0 web interface and genome browser provide more friendly, powerful, and informative ways to query and visualize the data. More importantly, MeT-DB v2.0 offers for the first time a series of tools specifically designed for understanding m6A functions. Met-DB V2.0 will be a valuable resource for m6A methyltranscriptome research. The Met-DB V2.0 database is available at http://compgenomics.utsa.edu/MeTDB/ and http://www.xjtlu.edu.cn/metdb2. PMID:29126312

  11. Feasibility and diagnostic performance of dual-tracer-guided sentinel lymph node biopsy in cT1-2N0M0 gastric cancer: a systematic review and meta-analysis of diagnostic studies.

    PubMed

    Huang, Ling; Wei, Tao; Chen, Junjun; Zhou, Donghui

    2017-05-16

    Dual-tracer-guided sentinel lymph node (SLN) biopsy may provide a promising diagnostic tool to assess accurately the status of lymph node metastasis in the surgical operation and assure the oncologic safety of the function or stomach preserving surgery. The diagnostic performance of this technology in recent studies varied. Thus, we conducted this meta-analysis. This systematic review and meta-analysis was registered at the PROSPERO. Eligible studies were searched in the PubMed, EMBASE, Web of Knowledge, and Cochrane Library databases. A random-effect model was used to pool the data. Summary receiver operator characteristic curves, analysis for publication bias, meta-regression, and subgroup analysis were also performed. The pooled SLN identification rate and sensitivity were 0.97 and 0.89. 99m Tc-human serum albumin with indocyanine green (ICG), 99m Tc-antimony sulfur colloid with ICG, performing SLN biopsy ≥15 min after dye injection, an SLN ≥5, the basin dissection, laparoscopic surgery, in studies conducted in Japan and studies published after 2012, were associated with higher sensitivity. CT1 stage, performing SLN biopsy ≥15 min after dye injection, in studies conducted in Japan and studies published after 2012, were related with a higher identification rate. Dual tracer is promising in SLN biopsy in gastric cancer, and the clinical application of SLN biopsy should be limited to the patients of cT1N0M0 gastric cancer. The combination of 99m Tc-human serum albumin and ICG as well as the combination of 99m Tc-antimony sulfur colloid and ICG may be the optimal tracer combination. However, it seems not justified to put this technique into routine clinical application recently. Some factors that might enhance diagnostic value are identified.

  12. A new series of oxycarbonate superconductors (Cu(0.5)C(0.5))(m)Ba(m+1)Ca(n-1)Cu(n)O2(m+n)+1

    NASA Technical Reports Server (NTRS)

    Takayama-Muromachi, E.; Kawashima, T.; Matsui, Y.

    1995-01-01

    We found a new series of oxycarbonate superconductors in the Ba-CaCu-C-O system under high pressure of 5 GPa. Their ideal formula is (Cu(0.5)C(0.5)(m)Ba(m+1)Ca(n-1)Cu(n)O2)((m+n)+1) ((Cu,C)-m(m+1)(n-1)n). Thus far, n = 3, 4 members of the m = 1 series, (Cu,C)-1223 and (Cu,C)-1234, have been prepared in bulk while n = 4, 5 members, (Cu,C)-2334 and (Cu,C)-2345, have been prepared for the m = 2 series. (Cu,C)-1223 shows superconductivity below 67 K while T(sub c)'s of other compounds are above 110 K. In particular, (Cu,C)-1234 has the highest T(sub c) of 117 K.

  13. Management of complex glottic stenosis in children with recurrent respiratory papillomatosis.

    PubMed

    Siegel, Bianca; Smith, Lee P

    2013-10-01

    To describe our management of complex glottic stenosis in tracheotomy dependent children with severe recurrent respiratory papillomatosis. Retrospective chart review at a tertiary care children's hospital. Three children with complex glottic stenosis secondary to severe recurrent respiratory papillomatosis were treated at our institution since 2011. Two patients had complete stenosis, and the third had near-complete stenosis. Two patients were managed using balloon dilation alone, and the third also underwent laryngotracheal reconstruction with posterior costal cartilage grafting. Two patients have been successfully decannulated and the third has been tolerating continuous tracheotomy capping for greater than twelve months. All three patients underwent aggressive debridement of papillomatosis and balloon dilation every 4-6 weeks until their burden of disease was controlled. In two patients, the glottic airway was patent, and the third continued to have complete restenosis between procedures and required laryngotracheoplasty with multiple post-operative dilation procedures to establish an adequate glottic airway. Severe laryngeal stenosis is a well-described complication of recurrent respiratory papillomatosis, but its management is not well-defined. Aggressive management of papillomatosis with frequent debridement is critical in successfully managing laryngeal stenosis. Balloon dilation alone may be surprisingly effective in these patients, and laryngotracheoplasty can be used as an adjunct procedure in those patients who fail balloon dilation. Given the quality of life issues and concerns regarding distal spread of disease with tracheotomies in these patients, we feel that aggressive management and early decannulation is in the patient's best interest. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  14. Post-treatment PSA < or = 0.2 ng/mL defines disease freedom after radiotherapy for prostate cancer using modern techniques.

    PubMed

    Critz, F A; Williams, W H; Holladay, C T; Levinson, A K; Benton, J B; Holladay, D A; Schnell, F J; Maxa, L S; Shrake, P D

    1999-12-01

    The prostate-specific antigen (PSA) definition of disease freedom after radiotherapy for prostate cancer is still in dispute. This report focuses on the PSA nadir achieved in men treated by modern radiotherapy techniques. From 1984 to 1994, 489 consecutive men with clinical Stage T1 -T2 prostate cancer were treated by simultaneous radiation: prostate iodine-125 implant followed by external beam radiation. A transperineal implant was performed on 143 men with Stage T1-T2NX, the focus of this study; 346 men with Stage T1-T2N0 had a retropubic implant. The median pretreatment PSA was 8.3 ng/mL (range 0.3 to 188). A rising PSA was defined as one that rose on three consecutive occasions above whatever nadir was achieved. A minimum 5-year follow-up (range 5 to 15) was reached by 453 men. After a minimum 5-year follow-up, 336 men had a nonrising PSA, and of this group, 107 had undergone simultaneous radiation by the transperineal implant technique. A PSA nadir of 0.2 ng/mL or less was achieved by 97% of the transperineally implanted men, and 3% had a nadir of 0.3 to 1.0 ng/mL. Of the 489 men, those who had a nadir of 0.2 ng/mL or less had a 92% nonrising PSA rate (P = 0.001) 10 years after treatment compared with a 41% rate for men who had a nadir of 0.3 to 1.0 ng/mL. All men whose nadir was greater than 1.0 ng/mL had recurrence. The median time to achieve the PSA nadir of 0.2 ng/mL was 27 months (range 3 to 102). Primarily on the basis of the results from men treated with simultaneous radiation using the transperineal technique, the definition of disease freedom for radiotherapy should be men who achieve and maintain a PSA nadir of 0.2 ng/mL or less.

  15. Pilot Study of the Use of Hybrid Multidimensional T2-Weighted Imaging-DWI for the Diagnosis of Prostate Cancer and Evaluation of Gleason Score.

    PubMed

    Sadinski, Meredith; Karczmar, Gregory; Peng, Yahui; Wang, Shiyang; Jiang, Yulei; Medved, Milica; Yousuf, Ambereen; Antic, Tatjana; Oto, Aytekin

    2016-09-01

    The objective of our study was to evaluate the role of a hybrid T2-weighted imaging-DWI sequence for prostate cancer diagnosis and differentiation of aggressive prostate cancer from nonaggressive prostate cancer. Twenty-one patients with prostate cancer who underwent preoperative 3-T MRI and prostatectomy were included in this study. Patients underwent a hybrid T2-weighted imaging-DWI examination consisting of DW images acquired with TEs of 47, 75, and 100 ms and b values of 0 and 750 s/mm(2). The apparent diffusion coefficient (ADC) and T2 were calculated for cancer and normal prostate ROIs at each TE and b value. Changes in ADC and T2 as a function of increasing the TE and b value, respectively, were analyzed. A new metric termed "PQ4" was defined as the percentage of voxels within an ROI that has increasing T2 with increasing b value and has decreasing ADC with increasing TE. ADC values were significantly higher in normal ROIs than in cancer ROIs at all TEs (p < 0.0001). With increasing TE, the mean ADC increased 3% in cancer ROIs and increased 12% in normal ROIs. T2 was significantly higher in normal ROIs than in cancer ROIs at both b values (p ≤ 0.0002). The mean T2 decreased with increasing b value in cancer ROIs (ΔT2 = -17 ms) and normal ROIs (ΔT2 = -52 ms). PQ4 clearly differentiated normal ROIs from prostate cancer ROIs (p = 0.0004) and showed significant correlation with Gleason score (ρ = 0.508, p < 0.0001). Hybrid MRI measures the response of ADC and T2 to changing TEs and b values, respectively. This approach shows promise for detecting prostate cancer and determining its aggressiveness noninvasively.

  16. The effect of bronchoscope rotation on tracheal tube orientation at the glottic level in a mannequin.

    PubMed

    Wong, David T; Yau, Brian; Thapar, Shikha; Adhikary, Sanjib D

    2010-10-01

    This study examined the effect of external fibreoptic bronchoscope (FOB) rotations on endotracheal tube (ETT) orientations at the glottic level. Using a mannequin, a nasal FOB was inserted for image capture. A second FOB with a preloaded ETT taped to its top was inserted orally into mid-trachea. The FOB with the taped ETT was rotated as a unit in the axial plane to five different external angles (-90°, -45°, 0°, +45°, +90°). At each external rotation, the ETT was advanced into the trachea. The image of the ETT at the glottic level was captured. Endotracheal tube orientation was quantified according to the glottic zone faced by the ETT. The ETT orientations were compared amongst the five external FOB rotations using the Kruskal-Wallis Test, while the ETT orientations at -90°, -45°, +45°, and +90° FOB rotations were compared with 0° rotation using the Mann-Whitney U test. There was a significant difference in the ETT orientations amongst the five FOB rotations (P < 0.001). The ETT orientations at -90°, -45°, +45°, and +90° FOB rotations were different from the 0° rotation (P < 0.001 for all comparisons). A -90° FOB rotation was most effective in turning the ETT tip away from the right laryngeal structures and the interarytenoid tissue. With the ETT loaded on a FOB, rotation of the FOB prior to advancing the ETT is effective in changing the ETT orientation at the glottis. A -90° FOB rotation is most effective in turning the ETT tip away from the right laryngeal structures and interarytenoid tissue.

  17. An Apparent Diffusion Coefficient Histogram Method Versus a Traditional 2-Dimensional Measurement Method for Identifying Non-Puerperal Mastitis From Breast Cancer at 3.0 T.

    PubMed

    Tang, Qi; Li, Qiang; Xie, Dong; Chu, Ketao; Liu, Lidong; Liao, Chengcheng; Qin, Yunying; Wang, Zheng; Su, Danke

    2018-05-21

    This study aimed to investigate the utility of a volumetric apparent diffusion coefficient (ADC) histogram method for distinguishing non-puerperal mastitis (NPM) from breast cancer (BC) and to compare this method with a traditional 2-dimensional measurement method. Pretreatment diffusion-weighted imaging data at 3.0 T were obtained for 80 patients (NPM, n = 27; BC, n = 53) and were retrospectively assessed. Two readers measured ADC values according to 2 distinct region-of-interest (ROI) protocols. The first protocol included the generation of ADC histograms for each lesion, and various parameters were examined. In the second protocol, 3 freehand (TF) ROIs for local lesions were generated to obtain a mean ADC value (defined as ADC-ROITF). All of the ADC values were compared by an independent-samples t test or the Mann-Whitney U test. Receiver operating characteristic curves and a leave-one-out cross-validation method were also used to determine diagnostic deficiencies of the significant parameters. The ADC values for NPM were characterized by significantly higher mean, 5th to 95th percentiles, and maximum and mode ADCs compared with the corresponding ADCs for BC (all P < 0.05). However, the minimum, skewness, and kurtosis ADC values, as well as ADC-ROITF, did not significantly differ between the NPM and BC cases. Thus, the generation of volumetric ADC histograms seems to be a superior method to the traditional 2-dimensional method that was examined, and it also seems to represent a promising image analysis method for distinguishing NPM from BC.

  18. Synthesis of Ferromagnetic Fe0.6 Mn0.4 O Nanoflowers as a New Class of Magnetic Theranostic Platform for In Vivo T1 -T2 Dual-Mode Magnetic Resonance Imaging and Magnetic Hyperthermia Therapy.

    PubMed

    Liu, Xiao Li; Ng, Cheng Teng; Chandrasekharan, Prashant; Yang, Hai Tao; Zhao, Ling Yun; Peng, Erwin; Lv, Yun Bo; Xiao, Wen; Fang, Jie; Yi, Jia Bao; Zhang, Huan; Chuang, Kai-Hsiang; Bay, Boon Huat; Ding, Jun; Fan, Hai Ming

    2016-08-01

    Uniform wüstite Fe0.6 Mn0.4 O nanoflowers have been successfully developed as an innovative theranostic agent with T1 -T2 dual-mode magnetic resonance imaging (MRI), for diagnostic applications and therapeutic interventions via magnetic hyperthermia. Unlike their antiferromagnetic bulk counterpart, the obtained Fe0.6 Mn0.4 O nanoflowers show unique room-temperature ferromagnetic behavior, probably due to the presence of an exchange coupling effect. Combined with the flower-like morphology, ferromagnetic Fe0.6 Mn0.4 O nanoflowers are demonstrated to possess dual-modal MRI sensitivity, with longitudinal relaxivity r1 and transverse relaxivity r2 as high as 4.9 and 61.2 mm(-1) s(-1) [Fe]+[Mn], respectively. Further in vivo MRI carried out on the mouse orthotopic glioma model revealed gliomas are clearly delineated in both T1 - and T2 -weighted MR images, after administration of the Fe0.6 Mn0.4 O nanoflowers. In addition, the Fe0.6 Mn0.4 O nanoflowers also exhibit excellent magnetic induction heating effects. Both in vitro and in vivo magnetic hyperthermia experimentation has demonstrated that magnetic hyperthermia by using the innovative Fe0.6 Mn0.4 O nanoflowers can induce MCF-7 breast cancer cell apoptosis and a complete tumor regression without appreciable side effects. The results have demonstrated that the innovative Fe0.6 Mn0.4 O nanoflowers can be a new magnetic theranostic platform for in vivo T1 -T2 dual-mode MRI and magnetic thermotherapy, thereby achieving a one-stop diagnosis cum effective therapeutic modality in cancer management. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Stereotactic hypofractionated radiotherapy in stage I (T1-2 N0 M0) non-small-cell lung cancer (NSCLC).

    PubMed

    Zimmermann, Frank B; Geinitz, Hans; Schill, Sabine; Thamm, Reinhard; Nieder, Carsten; Schratzenstaller, Ulrich; Molls, Michael

    2006-01-01

    Stereotactic Radiotherapy has the potential to produce high local control rates with low risk of severe lung toxicity. From December 2000 to January 2006, 68 inoperable patients (median age 76 years) with stage I NSCLC received definitive hSRT. A mean total dose of 37.5 Gy (24-40 Gy; 60%-isodose) in 3-5 fractions was applied. Immobilisation was carried out by means of a vacuum couch and low pressure foil (Medical Intelligence, Schwab München, Germany). Staging procedures were thoracic and abdominal CT-scan, FDG-PET and CT or MRI of the brain in all patients. Clinical target volume was the tumor as seen in lung windowing of CT and in FDG-PET. Organ movements (6-22 mm) and patient positioning in the couch (3-12 mm) were added as safety margin for the definition of the planning target volume (PTV), that was enclosed by the 60%-isodose. We observed four (6%) local tumor recurrences, resulting in an actuarial local tumor control rate of 96%, 88% and 88% after 1, 2 and 3 year follow-up. Nineteen patients died, with eight patients due to cancer (12%), two to local tumor progression alone. Cancer-specific survival is 96%, 82% and 73% at 1, 2 and 3 years. Eleven patients died from comorbidities, making a 53% overall 3-year survival. Fifty five percent of the patients were affected by mild acute and subacute side effects, with only 3% experiencing pneumonitis III degrees . Late effects were pneumonitis III degrees in 1%, rib fractures in 3%, and benign pleural effusion in 2 patients. Hypofractionated SRT is safe even in elderly patients with stage I NSCLC and significantly reduced lung capacity. It leads to high local control rates and should be offered to patients not amenable for curative resection.

  20. DS-8201a, a new HER2-targeting antibody-drug conjugate incorporating a novel DNA topoisomerase I inhibitor, overcomes HER2-positive gastric cancer T-DM1 resistance.

    PubMed

    Takegawa, Naoki; Nonagase, Yoshikane; Yonesaka, Kimio; Sakai, Kazuko; Maenishi, Osamu; Ogitani, Yusuke; Tamura, Takao; Nishio, Kazuto; Nakagawa, Kazuhiko; Tsurutani, Junji

    2017-10-15

    Anti-HER2 therapies are beneficial for patients with HER2-positive breast or gastric cancer. T-DM1 is a HER2-targeting antibody-drug conjugate (ADC) comprising the antibody trastuzumab, a linker, and the tubulin inhibitor DM1. Although effective in treating advanced breast cancer, all patients eventually develop T-DM1 resistance. DS-8201a is a new ADC incorporating an anti-HER2 antibody, a newly developed, enzymatically cleavable peptide linker, and a novel, potent, exatecan-derivative topoisomerase I inhibitor (DXd). DS-8201a has a drug-to-antibody-ratio (DAR) of 8, which is higher than that of T-DM1 (3.5). Owing to these unique characteristics and unlike T-DM1, DS-8201a is effective against cancers with low-HER2 expression. In the present work, T-DM1-resistant cells (N87-TDMR), established using the HER2-positive gastric cancer line NCI-N87 and continuous T-DM1 exposure, were shown to be susceptible to DS-8201a. The ATP-binding cassette (ABC) transporters ABCC2 and ABCG2 were upregulated in N87-TDMR cells, but HER2 overexpression was retained. Furthermore, inhibition of ABCC2 and ABCG2 by MK571 restored T-DM1 sensitivity. Therefore, resistance to T-DM1 is caused by efflux of its payload DM1, due to aberrant expression of ABC transporters. In contrast to DM1, DXd payload of DS-8201a inhibited the growth of N87-TDMR cells in vitro. This suggests that either DXd may be a poor substrate of ABCC2 and ABCG2 in comparison to DM1, or the high DAR of DS-8201a relative to T-DM1 compensates for increased efflux. Notably, N87-TDMR xenograft tumor growth was prevented by DS-8201a. In conclusion, the efficacy of DS-8201a as a treatment for patients with T-DM1-resistant breast or gastric cancer merits investigation. © 2017 UICC.

  1. Preoperative predictors of occult nodal disease in cT1N0 oral cavity squamous cell carcinoma: Review of 2623 cases.

    PubMed

    Zhan, Kevin Y; Morgan, Patrick F; Neskey, David M; Kim, Joanne J; Huang, Andrew T; Garrett-Mayer, Elizabeth; Day, Terry A

    2018-05-14

    Nodal disease predicts survival in oral cavity squamous cell carcinoma (SCC). Currently, no large studies on predictors of occult nodal disease in cT1N0 oral cavity SCC exist. The National Cancer Database (NCDB) review for cT1N0 oral cavity SCC with surgical resection and elective neck dissection (END). The number of patients found with occult nodal disease was 2623 (15.1%). In multivariable regression, female sex and tumor differentiation predict occult nodal disease. Occult nodal disease incidence was 5.9% in well-differentiated tumors, 17.4% in moderately differentiated tumors, and 28.5% in poorly differentiated tumor (P < .001). Women with oral tongue tumors had higher occult nodal disease (19.1%) than men (12%; P = .001). Adjusted odds ratios (aORs) for occult nodal disease in women were: aOR 1.26; 95% confidence interval (CI) 1.01-1.59; P = .045; moderately differentiated aOR 3.52; 95% CI 2.47-5.01; P < .001; and poorly differentiated aOR 6.25; 95% CI 4.17-9.38; P < .001. Sex and tumor differentiation significantly predict occult nodal disease. END is recommended for all moderately and poorly differentiated cT1N0 oral cavity SCC, regardless of the depth of invasion. One can consider not performing END in well-differentiated tumors. © 2018 Wiley Periodicals, Inc.

  2. Interim heterogeneity changes measured using entropy texture features on T2-weighted MRI at 3.0 T are associated with pathological response to neoadjuvant chemotherapy in primary breast cancer.

    PubMed

    Henderson, Shelley; Purdie, Colin; Michie, Caroline; Evans, Andrew; Lerski, Richard; Johnston, Marilyn; Vinnicombe, Sarah; Thompson, Alastair M

    2017-11-01

    To investigate whether interim changes in hetereogeneity (measured using entropy features) on MRI were associated with pathological residual cancer burden (RCB) at final surgery in patients receiving neoadjuvant chemotherapy (NAC) for primary breast cancer. This was a retrospective study of 88 consenting women (age: 30-79 years). Scanning was performed on a 3.0 T MRI scanner prior to NAC (baseline) and after 2-3 cycles of treatment (interim). Entropy was derived from the grey-level co-occurrence matrix, on slice-matched baseline/interim T2-weighted images. Response, assessed using RCB score on surgically resected specimens, was compared statistically with entropy/heterogeneity changes and ROC analysis performed. Association of pCR within each tumour immunophenotype was evaluated. Mean entropy percent differences between examinations, by response category, were: pCR: 32.8%, RCB-I: 10.5%, RCB-II: 9.7% and RCB-III: 3.0%. Association of ultimate pCR with coarse entropy changes between baseline/interim MRI across all lesions yielded 85.2% accuracy (area under ROC curve: 0.845). Excellent sensitivity/specificity was obtained for pCR prediction within each immunophenotype: ER+: 100%/100%; HER2+: 83.3%/95.7%, TNBC: 87.5%/80.0%. Lesion T2 heterogeneity changes are associated with response to NAC using RCB scores, particularly for pCR, and can be useful across all immunophenotypes with good diagnostic accuracy. • Texture analysis provides a means of measuring lesion heterogeneity on MRI images. • Heterogeneity changes between baseline/interim MRI can be linked with ultimate pathological response. • Heterogeneity changes give good diagnostic accuracy of pCR response across all immunophenotypes. • Percentage reduction in heterogeneity is associated with pCR with good accuracy and NPV.

  3. (Cu 0.5Tl 0.5)Ba 2Ca n-1 Cu n- yGe yO 2 n+4- δ ( n = 3, 4 and y = 0.5, 0.75, 1.0); superconductors with GeO 2 planes

    NASA Astrophysics Data System (ADS)

    Khan, Nawazish A.; Irfan, M.

    2008-12-01

    We have successfully synthesized germanium doped (Cu 0.5Tl 0.5)Ba 2Ca n-1 Cu n- yGe yO 2 n+4- δ ( n = 3, 4 and y = 0, 0.5, 0.75, 1.0) superconductors and investigated the effect of Ge doping on the superconducting properties of these compounds. The solubility of Ge till y = 1 in the CuO 2 planes of (Cu 0.5Tl 0.5)Ba 2Ca 2Cu 3- yGe yO 10- δ, have been found to give superconductivity above 77 K. To our surprise an enhanced superconductivity is observed with the doping of semiconductor germanium in some samples. The enhanced superconductivity associated with mixed CuO 2/GeO 2 planes can be extremely useful for the understanding of mechanism of superconductivity; since we very well know the properties of germanium based semiconductors.

  4. Pre-treatment functional MRI of breast cancer: T2* evaluation at 3 T and relationship to dynamic contrast-enhanced and diffusion-weighted imaging.

    PubMed

    Kousi, Evanthia; O'Flynn, Elizabeth A M; Borri, Marco; Morgan, Veronica A; deSouza, Nandita M; Schmidt, Maria A

    2018-05-31

    Baseline T2* relaxation time has been proposed as an imaging biomarker in cancer, in addition to Dynamic Contrast-Enhanced (DCE) MRI and diffusion-weighted imaging (DWI) parameters. The purpose of the current work is to investigate sources of error in T2* measurements and the relationship between T2* and DCE and DWI functional parameters in breast cancer. Five female volunteers and thirty-two women with biopsy proven breast cancer were scanned at 3 T, with Research Ethics Committee approval. T2* values of the normal breast were acquired from high-resolution, low-resolution and fat-suppressed gradient-echo sequences in volunteers, and compared. In breast cancer patients, pre-treatment T2*, DCE MRI and DWI were performed at baseline. Pathologically complete responders at surgery and non-responders were identified and compared. Principal component analysis (PCA) and cluster analysis (CA) were performed. There were no significant differences between T2* values from high-resolution, low-resolution and fat-suppressed datasets (p > 0.05). There were not significant differences between baseline functional parameters in responders and non-responders (p > 0.05). However, there were differences in the relationship between T2* and contrast-agent uptake in responders and non-responders. Voxels of similar characteristics were grouped in 5 clusters, and large intra-tumoural variations of all parameters were demonstrated. Breast T2* measurements at 3 T are robust, but spatial resolution should be carefully considered. T2* of breast tumours at baseline is unrelated to DCE and DWI parameters and contribute towards describing functional heterogeneity of breast tumours. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Lymph node involvement in gastric cancer for different tumor sites and T stage: Italian Research Group for Gastric Cancer (IRGGC) experience.

    PubMed

    Di Leo, Alberto; Marrelli, Daniele; Roviello, Franco; Bernini, Marco; Minicozzi, AnnaMaria; Giacopuzzi, Simone; Pedrazzani, Corrado; Baiocchi, Luca Gian; de Manzoni, Giovanni

    2007-09-01

    The aim of lymphadenectomy is to clear all the metastatic nodes achieving a complete removal of the tumor; nevertheless, its role in gastric cancer has been very much debated. The frequency of node metastasis in each lymphatic station according to the International Gastric Cancer Association, was studied in 545 patients who underwent D2 or D3 lymphadenectomy from June 1988 to December 2002. Upper third early cancers have shown an involvement of N2 celiac nodes in 25%. In advanced cancers, there was a high frequency of metastasis in the right gastroepiploic (from 10% in T2 to 50% in T4) and in the paraaortic nodes (26% in T2, 32% in T3, 38 % in T4). N3 left paracardial nodes involvement was observed in an important share of middle third tumors (17% in T3, 36% in T4). Splenic hilum nodes metastasis were common in T3 and T4 cancers located in the upper (39%) and middle (17%) stomach. N2 nodal involvement was frequent in lower third advanced cancers. Metastasis in M left paracardial and short gastric nodes were observed in a small percentage of cases. Given the nodal diffusion in our gastric cancer patients, extended lymphadenectomy is still a rationale to obtain radical resection.

  6. Phase 0 Trial of Itraconazole for Early-Stage Non-Small Cell Lung Cancer

    DTIC Science & Technology

    2015-10-01

    63 Male Caucasian T1bN0M0 Stage IA Undifferentiated carcinoma , favor Large cell 63 Female Caucasian T1aN0N0 Stage IA squamous cell carcinoma ... carcinoma ; and possibly prolongs survival in advanced non-small cell lung cancer (NSCLC). Insight into itraconazole mechanism and biomarkers will...study team members in which itraconazole resulted in tumor regression and Hh pathway antagonism in basal cell carcinoma ; and (3) a clinical trial in

  7. Breast MRI at 3.0 T in a high-risk familial breast cancer screening cohort: comparison with 1.5 T screening studies.

    PubMed

    Pickles, M D; Turnbull, L W

    2012-07-01

    The sensitivity of X-ray mammography for the detection of breast malignancy in younger females is lower than that of breast MRI; consequently, guidelines recommend annual MRI for patients with a significantly elevated lifetime risk. The improved signal-to-noise ratio obtainable at 3.0 T should result in data superior to those obtainable at 1.5 T. However, breast imaging on higher field strength systems poses specific problems. As a result, caution has been urged in the implementation of breast MRI at 3.0 T. The aim of this study was to determine if it is appropriate to use 3.0 T MRI in the screening of patients by comparing the summary statistics achieved by this 3.0 T MRI programme against the published results of 1.5 T screening studies. Over a 20-month period, 291 patients referred with an elevated familial risk of breast cancer were examined at 3.0 T. Resulting images were scored based on the Royal College of Radiologists Breast Group imaging classification. The reference standard was a combination of histology and follow-up imaging. Follow-up data were available in 267 patients. Analysis revealed positive and negative post-test probabilities of 28% [95% confidence intervals (CI); range, 10-60%] and 1% (95% CI; range, 0-2%), respectively. These results compared favourably against those of a recent meta-analysis [25.3% (95% CI; range, 18.4-33.8%) and 0.4% (95% CI; range, 0.2-0.9%), respectively]. Given the similar summary statistics between this work and the 1.5 T results, it would appear that screening of high-risk patients at 3.0 T has potential. Further studies should be undertaken to verify this result.

  8. Predictive value of Sox2 expression in transurethral resection specimens in patients with T1 bladder cancer.

    PubMed

    Ruan, Jun; Wei, Bingbing; Xu, Zhuoqun; Yang, Shudong; Zhou, You; Yu, Minhong; Liang, Jiabei; Jin, Ke; Huang, Xing; Lu, Peng; Cheng, Huan

    2013-03-01

    Sox2 is thought to be an important regulator of self-renewal in embryonic stem cell. According to the cancer stem cell (CSC) theory, the overexpression of Sox2 is potentially involved in carcinogenesis and could affect tumor recurrence and metastasis. Previous study proved Sox2 might be prognostic marker for multiple human malignancies. The purpose of this study was to investigate the clinicopathological significance of Sox2 expression in human non-muscle-invasive bladder cancer. We examined Sox2 expression in 32 paired non-muscle-invasive bladder cancer tissues and adjacent non-cancerous tissues by quantitative real-time RT-PCR (qrtRT-PCR). In addition, we analyzed Sox2 and Ki-67 expression in 126 non-muscle-invasive bladder cancer samples and bladder cancer cell line T24 by immunohistochemistry and immunofluorescence assays. The recurrence-free survival was determined by Kaplan-Meier method and log-rank test. Cox regression was adopted for univariate and multivariate analyses of prognostic factors. The expression of Sox2 was significantly increased in non-muscle-invasive bladder cancer tissues. Sox2 expression was significantly correlated with that of Ki-67 (P < 0.001). The expression of Sox2 was significantly associated with tumor size (P = 0.006), tumor number (P = 0.037), and tumor grade (P < 0.001). Patients with high Sox2 expression had significantly poorer recurrence-free survival (P = 0.0002) when compared with patients with the low expression of Sox2. On multivariate analysis, Sox2 expression and tumor grade were found to be independent prognostic factors for recurrence-free survival (P < 0.05). Our data suggested for the first time that the high expression of Sox2 may contribute to the development of non-muscle-invasive bladder cancer and serve as a novel prognostic marker in patients with T1 bladder cancer.

  9. Lymphatic and local spread of T1 and T2 pancreatic cancer. A study of autopsy material.

    PubMed Central

    Nagai, H; Kuroda, A; Morioka, Y

    1986-01-01

    Eight autopsy cases of pancreatic cancer (duct cell adenocarcinoma) with T1 and T2 primary tumors were studied histologically to examine the exact extent of lymphatic and local spread. Six of them had microscopic metastasis in grossly negative lymph nodes near the primary tumor. In addition, four of them had a few metastatic nodes in the para-aortic region. In cases with lymphatic metastases, the extent of cancer infiltration within lymphatic vessels, nerves, and/or connective tissues was almost the same as that of lymph node metastasis. Major vascular involvement was found in four cases. There was no case in which multicentricity or marked intraductal spread of cancer cells was observed in the pancreas. It has been suggested that most of T1 and T2 pancreatic cancers have a fairly widespread microscopic extension, although extremely small T1 cancers have a very limited extension. Images FIG. 2. FIGS. 4a-c. FIGS. 5a-c. PMID:3015059

  10. Non-contrast magnetic resonance imaging for bladder cancer: fused high b value diffusion-weighted imaging and T2-weighted imaging helps evaluate depth of invasion.

    PubMed

    Lee, Minsu; Shin, Su-Jin; Oh, Young Taik; Jung, Dae Chul; Cho, Nam Hoon; Choi, Young Deuk; Park, Sung Yoon

    2017-09-01

    To investigate the utility of fused high b value diffusion-weighted imaging (DWI) and T2-weighted imaging (T2WI) for evaluating depth of invasion in bladder cancer. We included 62 patients with magnetic resonance imaging (MRI) and surgically confirmed urothelial carcinoma in the urinary bladder. An experienced genitourinary radiologist analysed the depth of invasion (T stage <2 or ≥2) using T2WI, DWI, T2WI plus DWI, and fused DWI and T2WI (fusion MRI). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were investigated. Area under the curve (AUC) was analysed to identify T stage ≥2. The rate of patients with surgically confirmed T stage ≥2 was 41.9% (26/62). Sensitivity, specificity, PPV, NPV and accuracy were 50.0%, 55.6%, 44.8%, 60.6% and 53.2%, respectively, with T2WI; 57.7%, 77.8%, 65.2%, 71.8% and 69.4%, respectively, with DWI; 65.4%, 80.6%, 70.8%, 76.3% and 74.2%, respectively, with T2WI plus DWI and 80.8%, 77.8%, 72.4%, 84.9% and 79.0%, respectively, with fusion MRI. AUC was 0.528 with T2WI, 0.677 with DWI, 0.730 with T2WI plus DWI and 0.793 with fusion MRI for T stage ≥2. Fused high b value DWI and T2WI may be a promising non-contrast MRI technique for assessing depth of invasion in bladder cancer. • Accuracy of fusion MRI was 79.0% for T stage ≥2 in bladder cancer. • AUC of fusion MRI was 0.793 for T stage ≥2 in bladder cancer. • Diagnostic performance of fusion MRI was comparable with T2WI plus DWI. • As a non-contrast MRI technique, fusion MRI is useful for bladder cancer.

  11. Photoelectron spectroscopic study of the hydrated nucleoside anions: Uridine(-)(H(2)O)(n=0-2), cytidine(-)(H(2)O)(n=0-2), and thymidine(-)(H(2)O)(n=0,1).

    PubMed

    Li, Xiang; Wang, Haopeng; Bowen, Kit H

    2010-10-14

    The hydrated nucleoside anions, uridine(-)(H(2)O)(n=0-2), cytidine(-)(H(2)O)(n=0-2), and thymidine(-)(H(2)O)(n=0,1), have been prepared in beams and studied by anion photoelectron spectroscopy in order to investigate the effects of a microhydrated environment on parent nucleoside anions. Vertical detachment energies (VDEs) were measured for all eight anions, and from these, estimates were made for five sequential anion hydration energies. Excellent agreement was found between our measured VDE value for thymidine(-)(H(2)O)(1) and its calculated value in the companion article by S. Kim and H. F. Schaefer III.

  12. Photoelectron spectroscopic study of the hydrated nucleoside anions: Uridine-(H2O)n=0-2, cytidine-(H2O)n=0-2, and thymidine-(H2O)n=0,1

    NASA Astrophysics Data System (ADS)

    Li, Xiang; Wang, Haopeng; Bowen, Kit H.

    2010-10-01

    The hydrated nucleoside anions, uridine-(H2O)n=0-2, cytidine-(H2O)n=0-2, and thymidine-(H2O)n=0,1, have been prepared in beams and studied by anion photoelectron spectroscopy in order to investigate the effects of a microhydrated environment on parent nucleoside anions. Vertical detachment energies (VDEs) were measured for all eight anions, and from these, estimates were made for five sequential anion hydration energies. Excellent agreement was found between our measured VDE value for thymidine-(H2O)1 and its calculated value in the companion article by S. Kim and H. F. Schaefer III.

  13. Clinical and dosimetric implications of intensity-modulated radiotherapy for early-stage glottic carcinoma

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ward, Matthew Christopher, E-mail: wardm3@ccf.org; Pham, Yvonne D.; Kotecha, Rupesh

    2016-04-01

    Conventional parallel-opposed radiotherapy (PORT) is the established standard technique for early-stage glottic carcinoma. However, case reports have reported the utility of intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) with or without image guidance (image-guided radiotherapy, IGRT) in select patients. The proposed advantages of IMRT/VMAT include sparing of the carotid artery, thyroid gland, and the remaining functional larynx, although these benefits remain unclear. The following case study presents a patient with multiple vascular comorbidities treated with VMAT for early-stage glottic carcinoma. A detailed explanation of the corresponding treatment details, dose-volume histogram (DVH) analysis, and a review of the relevant literaturemore » are provided. Conventional PORT remains the standard of care for early-stage glottic carcinoma. IMRT or VMAT may be beneficial for select patients, although great care is necessary to avoid a geographical miss. Clinical data supporting the benefit of CRT are lacking. Therefore, these techniques should be used with caution and only in selected patients.« less

  14. Synthesis and structure of the extended phosphazane ligand [(1,4-C6H4){N(μ-PN(t)Bu)2N(t)Bu}2](4).

    PubMed

    Sevilla, Raquel; Less, Robert J; García-Rodríguez, Raúl; Bond, Andrew D; Wright, Dominic S

    2016-02-07

    The reaction of the phenylene-bridged precursor (1,4-C6H4)[N(PCl2)2]2 with (t)BuNH2 in the presence of Et3N gives the new ligand precursor (1,4-C6H4)[N(μ-N(t)Bu)2(PNH(t)Bu)2]2, deprotonation of which with Bu2Mg gives the novel tetraanion [(1,4-C6H4){N(μ-N(t)Bu)2(PN(t)Bu)2}2](4-).

  15. Liver acquisition with acceleration volume acquisition gadolinium-enhanced magnetic resonance combined with T2 sequences in the diagnosis of local recurrence of rectal cancer.

    PubMed

    Cao, Wuteng; Li, Fangqian; Gong, Jiaying; Liu, Dechao; Deng, Yanhong; Kang, Liang; Zhou, Zhiyang

    2016-11-22

    To investigate the efficacy of liver acquisition with acceleration volume acquisition (LAVA) gadolinium-enhanced magnetic resonance (MR) sequences and to assess its added accuracy in diagnosing local recurrence (LR) of rectal cancer with conventional T2-weighted fast spin echo (FSE) sequences. Pelvic MRI, including T2-weighted FSE sequences, gadolinium-enhanced sequences of LAVA and T1-weighted FSE with fat suppression, was performed on 225 patients with postoperative rectal cancer. Two readers evaluated the presence of LR according to "T2" (T2 sequences only), "T2 + LAVA-Gad" (LAVA and T2 imaging), and "T2 + T1-fs-Gad" (T1 fat suppression-enhanced sequence with T2 images). To evaluate diagnostic efficiency, imaging quality with LAVA and T1-fs-Gad by subjective scores and the signal intensity (SI) ratio. In the result, the SI ratio of LAVA was significantly higher than that of T1-fs-Gad (p = 0.0001). The diagnostic efficiency of "T2 + LAVA-Gad" was better than that of "T2 + T1-fs-Gad" (p = 0.0016 for Reader 1, p = 0.0001 for Reader 2) and T2 imaging only (p = 0.0001 for Reader 1; p = 0.0001 for Reader 2). Therefore, LAVA gadolinium-enhanced MR increases the accuracy of diagnosis of LR from rectal cancer and could replace conventional T1 gadolinium-enhanced sequences in the postoperative pelvic follow-up of rectal cancer.

  16. Safety and Tolerability of TAR-200 and Nivolumab in Subjects With Muscle-Invasive Bladder Cancer

    ClinicalTrials.gov

    2018-05-04

    Bladder Cancer TNM Staging Primary Tumor (T) T2; Bladder Cancer TNM Staging Primary Tumor (T) T2A; Bladder Cancer TNM Staging Primary Tumor (T) T2B; Bladder Cancer TNM Staging Primary Tumor (T) T3; Bladder Cancer TNM Staging Primary Tumor (T) T3A; Bladder Cancer TNM Staging Primary Tumor (T) T3B; Bladder Cancer TNM Staging Regional Lymph Node (N) N0; Bladder Cancer TNM Staging Regional Lymph Node (N) N1; Bladder Cancer TNM Staging Distant Metastasis (M) M0

  17. Potent CD4+ T-cell epitope P30 enhances HER2/neu-engineered dendritic cell-induced immunity against Tg1-1 breast cancer in transgenic FVBneuN mice by enhanced CD4+ T-cell-stimulated CTL responses.

    PubMed

    Xie, Y; Chen, Y; Ahmed, K A; Li, W; Ahmed, S; Sami, A; Chibbar, R; Tang, X; Tao, M; Xu, J; Xiang, J

    2013-10-01

    One of the major obstacles in human epidermal growth factor receptor (HER)-2/neu-specific trastuzumab immunotherapy of HER2/neu-positive breast cancer is the development of trastuzumab resistance, warranting the search for other therapeutic strategies. Although dendritic cell (DC) vaccines have been extensively applied in clinical trials for cancer treatment, the vaccination efficacy is still limited, mostly because DC vaccines are not sufficient to break tumor-associated antigen-specific self-immune tolerance in cancer patients. P30 (FNNFTVSFWLRVPKVSASHLE) derived from tetanus toxin is a universally potent CD4(+) T helper epitope capable of enhancing CD8(+) cytotoxic T-lymphocyte (CTL) responses. In this study, we constructed two recombinant adenoviral vectors (AdVs), AdVOVA-P30 and AdVHER2/neu-P30, expressing ovalbumin (OVA)-P30 and HER2/neu-P30. In order to enhance DC vaccine efficacy, we transfected mouse bone marrow (BM)-derived DCs with AdVOVA-P30 and AdVHER2/neu-P30 to generate engineered DCOVA-P30 and DCHER2/neu-P30 vaccines, respectively. We, then, compared CD4(+) and CD8(+) T-cell responses and antitumor immunity derived from DCOVA-P30 and DCHER2/neu-P30 vaccination in wild-type C57BL/6 and transgenic FVBneuN mice, respectively. We demonstrate that engineered DCOVA-P30 vaccine stimulates more efficient CD4(+) and CD8(+) T-cell responses than DCOVA in C57BL/6 mice. Interestingly, the increased DCOVA-P30-induced CTL responses are mainly contributed by enhanced CD4(+) T-cell-stimulated CTL proliferation. We show that DCOVA-P30 vaccine also stimulates more efficient therapeutic immunity against OVA-expressing BL6-10OVA melanoma than DCOVA in C57BL/6 mice. In addition, we demonstrate that DCHER2/neu-P30 vaccine stimulates more efficient CD4(+) and CD8(+) T-cell responses and protective immunity against HER2/neu-expressing Tg1-1 breast cancer than DCHER2/neu in transgenic FVBneuN mice with HER2/neu-specific self-immune tolerance. Therefore, the engineered DCHER

  18. Significant Association of the MDM2 T309G Polymorphism with Breast Cancer Risk in a Turkish Population

    PubMed

    Yilmaz, Meral; Tas, Ayca; Donmez, Gonca; Kacan, Turgut; Silig, Yavuz

    2018-04-27

    Background: Breast cancer is a leading cause of death in women worldwide. Genetic polymorphisms have been reported to be important etiological factors. Murine double minute 2 (MDM2) T309G interacts with p53 and mutations in p53 are present in approximately 50% of all cancers. However, it has been reported that effect of the polymorphism on breast cancer risk may vary in different populations. Here, we therefore investigated whether there is an association between MDM2 T309G (rs2279744) polymorphism and breast cancer in a Turkish population. Materials and Methods: We analysed 110 patients with breast cancer and 138 matched? controls. For genotyping, polymerase chain reaction and restriction length fragment polymorphism methods were used. Results: A significant difference was observed between case and control groups with regard to the distribution of the MDM2 T309G polymorphism (p<0.05). There was a significantly higher frequency of the TT genotype in the control group (p=0.028; OR, 2.42; 95% CI, 1.09-5.37). However, we did not find any relationships among tumor grade and metastasis status and this polymorphism. Conclusion: This study indicates that the MDM2 T309G polymorphism GG genotype and the TG+GG combination may be risk factors for breast cancer in our Turkish population. Creative Commons Attribution License

  19. Diffusion-weighted magnetic resonance imaging combined with T2-weighted images in the detection of small breast cancer: a single-center multi-observer study.

    PubMed

    Wu, Lian-Ming; Chen, Jie; Hu, Jiani; Gu, Hai-Yan; Xu, Jian-Rong; Hua, Jia

    2014-02-01

    Breast cancer is the most common cancer in women worldwide. However, it remains a difficult diagnosis problem to differentiate between benign and malignant breast lesions, especially in small early breast lesions. To assess the diagnostic value of diffusion-weighted imaging (DWI) combined with T2-weighted imaging (T2WI) for small breast cancer characterization. Fifty-eight patients (65 lesions) with a lesion <2 cm in diameter underwent 3.0 Tesla breast magnetic resonance imaging (MRI) including DWI and histological analysis. Three observers with varying experience levels reviewed MRI. The probability of breast cancer in each lesion on MR images was recorded with a 5-point scale. Areas under the receiver-operating characteristic curve (AUCs) were compared by using the Z test; sensitivity and specificity were determined with the Z test after adjusting for data clustering. AUC of T2WI and DWI (Observer 1, 0.95; Observer 2, 0.91; Observer 3, 0.83) was greater than that of T2WI (Observer 1, 0.80; Observer 2, 0.74; Observer 3, 0.70) for all observers (P < 0.0001 in all comparisons). Sensitivity of T2WI and DWI (Observer 1, 90%; Observer 2, 93%; and Observer 3, 86%) was greater than that of T2WI alone (Observer 1, 76%; Observer 2, 83%; Observer 3, 79%) for all observers (P < 0.0001 in all comparisons). Specificity of T2WI and DWI was greater than that of T2WI alone for observer 1 (89% vs. 72%, P < 0.01) and observer 2 (94% vs. 78%, P < 0.001). DWI combined with T2WI can improve the diagnostic performance of MRI in small breast cancer characterization. It should be considered selectively in the preoperative evaluation of patients with small lesions of the breast.

  20. RACIAL DISPARITIES IN COLORECTAL CANCER INCIDENCE BY TYPE 2 DIABETES MELLITUS STATUS

    PubMed Central

    Cavicchia, Philip P; Adams, Swann A; Steck, Susan E; Hussey, James R; Liu, Jihong; Daguisé, Virginie G; Hebert, James R

    2012-01-01

    Purpose Type 2 diabetes mellitus (T2DM) prevalence has increased dramatically in the United States since the early 1970s. Though T2DM is known to be associated with colorectal cancer (CRC), information on racial differences in the relationship between T2DM and CRC is limited. Methods Using a retrospective cohort design we compared the association between T2DM and CRC, including subsites of the colon, in African Americans (AAs) and European Americans (EAs) in South Carolina, a region with large racial disparities in rates of both diseases. A total of 91,836 individuals who were ≥30 years old on January 1, 1990 and had ≥12 months of South Carolina Medicaid eligibility between January 1, 1990 and December 31, 1995 were included in the analyses. Cancer data from 1996 to 2007, included information on anatomic subsite. Results Subjects who had T2DM (n=6,006) were >50% more likely to be diagnosed with colon cancer compared to those without T2DM (n=85,681). The association between T2DM and colon cancer was higher in AAs [odds ratio (OR) = 1.72 (95% Confidence Interval:1.21,2.46); n=47,984] than among EAs (OR = 1.24; 0.73,2.11; n=43,703). Overall, individuals with T2DM were over twice as likely to be diagnosed with in situ or local colon cancer (OR = 2.12; 1.40,3.22; n=191) compared to those without T2DM, with a higher likelihood among AAs (OR = 2.49;1.52,4.09; n=113). Conclusions Results from a Medicaid population in a high-risk region of the country, showed an increased likelihood of CRC with T2DM and suggest a racial disparity that disfavors AAs and provides further impetus for efforts aimed at diabetes prevention in this group. PMID:23197224

  1. Preoperative chemotherapy for T2 breast cancer is associated with improved surgical outcome.

    PubMed

    Karanlik, H; Ozgur, I; Cabioglu, N; Sen, F; Erturk, K; Kilic, B; Onder, S; Deniz, M; Yavuz, E; Aydiner, A

    2015-09-01

    The aim of this study is to compare the clinical outcome in T2 breast cancer patients who underwent preoperative chemotherapy (PC) and who did not. The study also tried to define a subgroup of patients, who are more beneficial after PC in terms of lower re-excision rates, better cosmetic results and local recurrence free survival. 251 consecutive patients treated for nonmetastatic T2 invasive breast cancer were analyzed retrospectively. Of those; 141 underwent primary surgery (PS) followed by chemotherapy, whereas 110 were treated with combination of PC and surgery. The patients who were treated with PC had a significantly higher incidence of negative margins and lower rate of re-excision (5% vs. 16%, p = 0.02). Of all patients attempted breast conserving surgery (BCS), patients in the PC group were more likely to undergo BCS as their definitive operation compared to patients with PS group (BCS rates; PC group: 99% vs. PS group: 92%, p = 0.05). Multifocal disease (OR: 7, 95% Cl, 2.7-18.4, p = 0.0001) and PC (OR = 0.2; 95% CI, 0.06-0.72, p = 0.01) were factors associated with margin positivity in patients treated with BCS. There was no statistically significant difference in 5 year local-recurrence free survival rates between 2 groups. Our study shows that PC significantly decreases the re-excision in patients undergoing BCS with primary T2 breast tumors. This data suggests that any patient with a tumor greater than 2 cm might be considered for PC to increase BCS success with final negative margins. Copyright © 2015. Published by Elsevier Ltd.

  2. Total Laryngectomy Versus Larynx Preservation for T4a Larynx Cancer: Patterns of Care and Survival Outcomes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Grover, Surbhi; Swisher-McClure, Samuel; Mitra, Nandita

    2015-07-01

    Purpose: To examine practice patterns and compare survival outcomes between total laryngectomy (TL) and larynx preservation chemoradiation (LP-CRT) in the setting of T4a larynx cancer, using a large national cancer registry. Methods and Materials: Using the National Cancer Database, we identified 969 patients from 2003 to 2006 with T4a squamous cell larynx cancer receiving definitive treatment with either initial TL plus adjuvant therapy or LP-CRT. Univariate and multivariable logistic regression were used to assess predictors of undergoing surgery. Survival outcomes were compared using Kaplan-Meier and propensity score–adjusted and inverse probability of treatment–weighted Cox proportional hazards methods. Sensitivity analyses were performed tomore » account for unmeasured confounders. Results: A total of 616 patients (64%) received LP-CRT, and 353 (36%) received TL. On multivariable logistic regression, patients with advanced nodal disease were less likely to receive TL (N2 vs N0, 26.6% vs 43.4%, odds ratio [OR] 0.52, 95% confidence interval [CI] 0.37-0.73; N3 vs N0, 19.1% vs 43.4%, OR 0.23, 95% CI 0.07-0.77), whereas patients treated in high case-volume facilities were more likely to receive TL (46.1% vs 31.5%, OR 1.78, 95% CI 1.27-2.48). Median survival for TL versus LP was 61 versus 39 months (P<.001). After controlling for potential confounders, LP-CRT had inferior overall survival compared with TL (hazard ratio 1.31, 95% CI 1.10-1.57), and with the inverse probability of treatment–weighted model (hazard ratio 1.25, 95% CI 1.05-1.49). This survival difference was shown to be robust on additional sensitivity analyses. Conclusions: Most patients with T4a larynx cancer receive LP-CRT, despite guidelines suggesting TL as the preferred initial approach. Patients receiving LP-CRT had more advanced nodal disease and worse overall survival. Previous studies of (non-T4a) locally advanced larynx cancer showing no difference in survival between LP-CRT and TL

  3. Noninvasive monitoring of cancer therapy induced activated T cells using [18F]FB-IL-2 PET imaging.

    PubMed

    Hartimath, S V; Draghiciu, O; van de Wall, S; Manuelli, V; Dierckx, R A J O; Nijman, H W; Daemen, T; de Vries, E F J

    2017-01-01

    Cancer immunotherapy urgently calls for methods to monitor immune responses at the site of the cancer. Since activated T lymphocytes may serve as a hallmark for anticancer responses, we targeted these cells using the radiotracer N-(4-[ 18 F]fluorobenzoyl)-interleukin-2 ([ 18 F]FB-IL-2) for positron emission tomography (PET) imaging. Thus, we noninvasively monitored the effects of local tumor irradiation and/or immunization on tumor-infiltrating and systemic activated lymphocytes in tumor-bearing mice. A 10- and 27-fold higher [ 18 F]FB-IL-2 uptake was observed in tumors of mice receiving tumor irradiation alone or in combination with immunization, respectively. This increased uptake was extended to several non-target tissues. Administration of the CXCR4 antagonist AMD3100 reduced tracer uptake by 2.8-fold, indicating a CXCR4-dependent infiltration of activated T lymphocytes upon cancer treatment. In conclusion, [ 18 F]FB-IL-2 PET can serve as a clinical biomarker to monitor treatment-induced infiltration of activated T lymphocytes and, on that basis, may guide cancer immunotherapies.

  4. Correlation Between Magnetic Resonance Imaging-Based Evaluation of Extramural Vascular Invasion and Prognostic Parameters of T3 Stage Rectal Cancer.

    PubMed

    Yu, Jing; Huang, Dong-Ya; Xu, Hui-Xin; Li, Yang; Xu, Qing

    2016-01-01

    The aim of this study was to analyze the correlation between magnetic resonance imaging-based extramural vascular invasion (EMVI) and the prognostic clinical and histological parameters of stage T3 rectal cancers. Eighty-six patients with T3 stage rectal cancer who received surgical resection without neoadjuvant therapy were included. Magnetic resonance imaging-based EMVI scores were determined. Correlations between the scores and pretreatment carcinoembryonic antigen levels, tumor differentiation grade, nodal stage, and vascular endothelial growth factor expression were analyzed using Spearman rank coefficient analysis. Magnetic resonance imaging-based EMVI scores were statistically different (P = 0.001) between histological nodal stages (N0 vs N1 vs N2). Correlations were found between magnetic resonance imaging-based EMVI scores and tumor histological grade (rs = 0.227, P = 0.035), histological nodal stage (rs = 0.524, P < 0.001), and vascular endothelial growth factor expression (rs = 0.422; P = 0.016). Magnetic resonance imaging-based EMVI score is correlated with prognostic parameters of T3 stage rectal cancers and has the potential to become an imaging biomarker of tumor aggressiveness. Magnetic resonance imaging-based EMVI may be useful in helping the multidisciplinary team to stratify T3 rectal cancer patients for neoadjuvant therapies.

  5. Reference-tissue correction of T2-weighted signal intensity for prostate cancer detection

    NASA Astrophysics Data System (ADS)

    Peng, Yahui; Jiang, Yulei; Oto, Aytekin

    2014-03-01

    The purpose of this study was to investigate whether correction with respect to reference tissue of T2-weighted MRimage signal intensity (SI) improves its effectiveness for classification of regions of interest (ROIs) as prostate cancer (PCa) or normal prostatic tissue. Two image datasets collected retrospectively were used in this study: 71 cases acquired with GE scanners (dataset A), and 59 cases acquired with Philips scanners (dataset B). Through a consensus histology- MR correlation review, 175 PCa and 108 normal-tissue ROIs were identified and drawn manually. Reference-tissue ROIs were selected in each case from the levator ani muscle, urinary bladder, and pubic bone. T2-weighted image SI was corrected as the ratio of the average T2-weighted image SI within an ROI to that of a reference-tissue ROI. Area under the receiver operating characteristic curve (AUC) was used to evaluate the effectiveness of T2-weighted image SIs for differentiation of PCa from normal-tissue ROIs. AUC (+/- standard error) for uncorrected T2-weighted image SIs was 0.78+/-0.04 (datasets A) and 0.65+/-0.05 (datasets B). AUC for corrected T2-weighted image SIs with respect to muscle, bladder, and bone reference was 0.77+/-0.04 (p=1.0), 0.77+/-0.04 (p=1.0), and 0.75+/-0.04 (p=0.8), respectively, for dataset A; and 0.81+/-0.04 (p=0.002), 0.78+/-0.04 (p<0.001), and 0.79+/-0.04 (p<0.001), respectively, for dataset B. Correction in reference to the levator ani muscle yielded the most consistent results between GE and Phillips images. Correction of T2-weighted image SI in reference to three types of extra-prostatic tissue can improve its effectiveness for differentiation of PCa from normal-tissue ROIs, and correction in reference to the levator ani muscle produces consistent T2-weighted image SIs between GE and Phillips MR images.

  6. Spatially resolved H2 emission from the disk around T Tau N

    NASA Astrophysics Data System (ADS)

    Gustafsson, M.; Labadie, L.; Herbst, T. M.; Kasper, M.

    2008-09-01

    Context: Molecular hydrogen is the main constituent of circumstellar disks and could be an important tracer for the evolution and structure of such disks. So far, H2 has only been detected in a few disks and only through spectroscopic observations, resulting in a limited knowledge of the spatial distribution of the H2 emitting gas. Aims: We report the detection of quiescent H2 emission in a spatially resolved ring-like structure within 100 AU of T Tau N. We present evidence to show that the emission most likely arises from shocks in the atmosphere of a nearly face-on disk around T Tau N. Methods: Using high spatial resolution 3D spectroscopic K-band data, we trace the spatial distribution of several H2 NIR rovibrational lines in the vicinity of T Tau N. We examine the structure of the circumstellar material around the star through SED modeling. Then, we use models of shocks and UV+X-ray irradiation to reproduce the H2 line flux and line ratios in order to test how the H2 is excited. Results: We detect weak H2 emission from the v=1{-}0 S(0), S(1), Q(1) lines and the v=2{-}1 S(1) line in a ring-like structure around T Tau N between 0.1 arcsec ( 15 AU) and 0.7 arcsec ( 100 AU) from the star. The v=1{-}0 S(0) and v=2{-}1 S(1) lines are detected only in the outer parts of the ring structure. Closer to the star, the strong continuum limits our sensitivity to these lines. The total flux of the v=1{-}0 S(1) line is 1.8 × 10-14 erg s-1 cm-2, similar to previous measurements of H2 in circumstellar disks. The velocity of the H2 emitting gas around T Tau N is consistent with the rest velocity of the star, and the H2 does not seem to be part of a collimated outflow. Both shocks impinging on the surface of a disk and irradiation of a disk by UV-photons and X-rays from the central star are plausible candidates for the H2 excitation mechanism. However, irradiation should not create a large degree of excitation at radii larger than 20 AU. Most likely the H2 emission arises in the

  7. Regional hyperthermia in conjunction with definitive radiotherapy against recurrent or locally advanced prostate cancer T3 pN0 M0.

    PubMed

    Tilly, Wolfgang; Gellermann, Johanna; Graf, Reinhold; Hildebrandt, Bert; Weissbach, Lothar; Budach, Volker; Felix, Roland; Wust, Peter

    2005-01-01

    Since long-term results of the standard treatment of locally advanced or recurrent prostatic carcinoma are unsatisfactory, the role for additional regional hyperthermia was evaluated in a phase I/II study. From 08/1996 to 03/2000, 22 patients were treated by a standard irradiation regimen (68.4 Gy) in combination with regional hyperthermia (weekly, five to six times), and five of 22 patients received short-term (neoadjuvant) hormonal treatment. Of these, 15 patients had primary prostatic carcinoma T3 pN0 M0 and seven a histologically confirmed local recurrence after radical prostatectomy. Feasibility of hyperthermia, and acute/late toxicity as well as long-term follow-up (prostate- specific antigen [PSA] control, overall survival) were analyzed. Clinical endpoints were correlated with thermal parameters. Mean maximum temperatures along the urethra of 41.4 degrees C (41.0 degrees C for the recurrences), and mean T(90) values of 40.7 degrees C could be achieved. Severe acute toxicity of grade 3 occurred at the rectum in three, at the urethra in four, at the intestine in one, and a burn induced by hyperthermia in one of 22 patients. Late toxicity was only observed rectally in one patient (grade 3) and at the urethra in two patients (grade 2). There was no correlation between thermal parameters and any toxicity. The survival curves showed a PSA control for primary prostatic carcinoma > 50% after 6 years, but no long-term PSA control for the recurrences. Overall survival after 6 years was 95% for primary carcinoma, and 60% for the recurrences. There was a clear correlation between higher temperatures or thermal doses with long-term PSA control. Regional hyperthermia might be a low-toxicity approach to increase PSA control of common treatment schedules. Further evaluation, in particular employing improved hyperthermia technology, is worthwhile.

  8. Comparative study of microelectrode recording-based STN location and MRI-based STN location in low to ultra-high field (7.0 T) T2-weighted MRI images

    NASA Astrophysics Data System (ADS)

    Verhagen, Rens; Schuurman, P. Richard; van den Munckhof, Pepijn; Fiorella Contarino, M.; de Bie, Rob M. A.; Bour, Lo J.

    2016-12-01

    Objective. The correspondence between the anatomical STN and the STN observed in T2-weighted MRI images used for deep brain stimulation (DBS) targeting remains unclear. Using a new method, we compared the STN borders seen on MRI images with those estimated by intraoperative microelectrode recordings (MER). Approach. We developed a method to automatically generate a detailed estimation of STN shape and the location of its borders, based on multiple-channel MER measurements. In 33 STNs of 19 Parkinson patients, we quantitatively compared the dorsal and lateral borders of this MER-based STN model with the STN borders visualized by 1.5 T (n = 14), 3.0 T (n = 10) and 7.0 T (n = 9) T2-weighted MRI. Main results. The dorsal border was identified more dorsally on coronal T2 MRI than by the MER-based STN model, with a significant difference in the 3.0 T (range 0.97-1.19 mm) and 7.0 T (range 1.23-1.25 mm) groups. The lateral border was significantly more medial on 1.5 T (mean: 1.97 mm) and 3.0 T (mean: 2.49 mm) MRI than in the MER-based STN; a difference that was not found in the 7.0 T group. Significance. The STN extends further in the dorsal direction on coronal T2 MRI images than is measured by MER. Increasing MRI field strength to 3.0 T or 7.0 T yields similar discrepancies between MER and MRI at the dorsal STN border. In contrast, increasing MRI field strength to 7.0 T may be useful for identification of the lateral STN border and thereby improve DBS targeting.

  9. Auroral excitation of the N2 2P(0,0) and VK(0,9) bands

    NASA Technical Reports Server (NTRS)

    Solomon, Stanley C.

    1989-01-01

    The low-energy secondary electron flux caused by auroral electron precipitation is examined using data from the Atmosphere Explorer C satellite. An energetic electron transport algorithm is used to compute the differential electron flux produced by measured primaries. Emissions of N2 in the 2P(0,0) band at 337 nm and the VK(0,9) band at 335 nm predicted by the model are compared with photometric observation of their combined volume emission rate altitude profile made by the visible airglow experiment. Reasonable correspondence between model and measurement is obtained. Ratios of emissions at 337 nm and 630 nm to the N2(+) 1N(0,0) band at 428 nm are also studied. It is concluded that the 337/428 nm ratio responds to changes in the characteristic energy of primary auroral electrons only insofar as part of the 337 nm brightness is due to N2 VK(0,9) emission. The 630/428 nm ratio, which is strongly dependent on characteristic energy, also varies significantly with changes in atomic oxygen density.

  10. A non-randomized confirmatory trial of segmentectomy for clinical T1N0 lung cancer with dominant ground glass opacity based on thin-section computed tomography (JCOG1211).

    PubMed

    Aokage, Keiju; Saji, Hisashi; Suzuki, Kenji; Mizutani, Tomonori; Katayama, Hiroshi; Shibata, Taro; Watanabe, Syunichi; Asamura, Hisao

    2017-05-01

    Lobectomy has been the standard surgery for even stage I lung cancer since the validity of limited resection for stage I lung cancer was denied by the randomized study reported in 1995. The aim of this non-randomized confirmatory going on since September 2013 is to confirm the efficacy of a segmentectomy for clinical T1N0 lung cancer with dominant ground glass opacity based on thin-slice computed tomography. A total of 390 patients from 42 Japanese institutions are recruited within 4 years. The primary endpoint of this study is a 5-year relapse-free survival in all of the patients who undergo a segmentectomy for a lung nodule. The secondary endpoints are overall survival, annual relapse-free survival, disease-free survival, proportion of local relapse, postoperative pulmonary function, proportion of segmentectomy completion, proportion of R0 resection completion by segmentectomy, adverse events, and serious adverse events. This trial has been registered at the UMIN Clinical Trials Registry as UMIN000011819 ( http://www.umin.ac.jp/ctr/ ). Patient's accrual has been already finished in November, 2015 and the primary analysis will be performed in 2021. This study is one of the pivotal trial of lung segmentectomy for early lung cancer. The result will provide a clear evidence for our daily clinics and will be possible contribution to preserving pulmonary function for lung cancer patients.

  11. Tumor budding as a novel predictor of occult metastasis in cT2N0 tongue squamous cell carcinoma.

    PubMed

    Sakata, Junki; Yamana, Keisuke; Yoshida, Ryoji; Matsuoka, Yuichiro; Kawahara, Kenta; Arita, Hidetaka; Nakashima, Hikaru; Nagata, Masashi; Hirosue, Akiyuki; Kawaguchi, Sho; Gohara, Shunsuke; Nagao, Yuka; Hiraki, Akimitsu; Shinohara, Masanori; Toya, Ryo; Murakami, Ryuji; Nakayama, Hideki

    2018-06-01

    Occult neck metastasis is an important prognostic factor in patients with tongue squamous cell carcinoma (TSCC) who are deemed clinically negative for neck metastasis. The purpose of this study was to identify predictive factors for occult neck metastasis arising from TSCC and to determine patient prognosis. Ninety-seven patients with cT2N0 TSCC who underwent surgical resection of their primary lesion as initial therapy were enrolled in this retrospective study. Cutoff values for depth of invasion (≥3.3 mm) and the tumor budding score (≥4) were determined using receiver operator characteristic analyses. Univariate and multivariate analyses revealed that a tumor budding score ≥4 is a significant independent predictive factor for the occurrence of occult neck metastasis, which in turn is a significant independent prognostic factor. When evaluating tumor budding, we demonstrated greater interobserver and intraobserver agreement when using immunohistochemical staining for cytokeratin AE1/AE3 than with hematoxylin and eosin staining (HE). We conclude that the evaluation of tumor budding is effective for identifying populations at high risk of occult neck metastasis, which will enable the planning of appropriate therapeutic strategies for patients with cT2N0 TSCC. Furthermore, cytokeratin staining is recommended over HE staining for simpler and more accurate evaluation of tumor budding. Copyright © 2018 Elsevier Inc. All rights reserved.

  12. Human Epidermal Growth Factor Receptor 2 Expression in Unresectable Gastric Cancers: Relationship with CT Characteristics.

    PubMed

    Lee, Jeong Sub; Kim, Se Hyung; Im, Seock-Ah; Kim, Min A; Han, Joon Koo

    2017-01-01

    To retrospectively analyze the qualitative CT features that correlate with human epidermal growth factor receptor 2 (HER2)-expression in pathologically-proven gastric cancers. A total of 181 patients with pathologically-proven unresectable gastric cancers with HER2-expression (HER2-positive [n = 32] and negative [n = 149]) were included. CT features of primary gastric and metastatic tumors were reviewed. The prevalence of each CT finding was compared in both groups. Thereafter, binary logistic regression determined the most significant differential CT features. Clinical outcomes were compared using Kaplan-Meier method. HER2-postive cancers showed lower clinical T stage (21.9% vs. 8.1%; p = 0.015), hyperattenuation on portal phase (62.5% vs. 30.9%; p = 0.003), and was more frequently metastasized to the liver (62.5% vs. 32.2%; p = 0.001), than HER2-negative cancers. On binary regression analysis, hyperattenuation of the tumor (odds ratio [OR], 4.68; p < 0.001) and hepatic metastasis (OR, 4.43; p = 0.001) were significant independent factors that predict HER2-positive cancers. Median survival of HER2-positive cancers (13.7 months) was significantly longer than HER2-negative cancers (9.6 months) ( p = 0.035). HER2-positive gastric cancers show less-advanced T stage, hyperattenuation on the portal phase, and frequently metastasize to the liver, as compared to HER2-negative cancers.

  13. Esophageal Cancer: Associations with pN+

    PubMed Central

    Rice, Thomas W.; Ishwaran, Hemant; Hofstetter, Wayne L.; Schipper, Paul H.; Kesler, Kenneth A.; Law, Simon; Lerut, Toni E.M.R.; Denlinger, Chadrick E.; Salo, Jarmo A.; Scott, Walter J.; Watson, Thomas J.; Allen, Mark S.; Chen, Long-Qi; Rusch, Valerie W.; Cerfolio, Robert J.; Luketich, James D.; Duranceau, Andre; Darling, Gail E.; Pera, Manuel; Apperson-Hansen, Carolyn; Blackstone, Eugene H.

    2017-01-01

    Objectives 1) To identify the association of positive lymph node metastases (pN+), number of positive nodes, and pN subclassification with cancer, treatment, patient, geographic, and institutional variables, and 2) to recommend extent of lymphadenectomy needed to accurately detect pN+ for esophageal cancer. Summary Background Data Limited data and traditional analytic techniques have precluded identifying intricate associations of pN+ with other cancer, treatment, and patient characteristics. Methods Data on 5,806 esophagectomy patients from the Worldwide Esophageal Cancer Collaboration (WECC) were analyzed by Random Forest machine learning techniques. Results pN+, number of positive nodes, and pN subclassification were associated with increasing depth of cancer invasion (pT), increasing cancer length, decreasing cancer differentiation (G), and more regional lymph nodes resected. Lymphadenectomy necessary to accurately detect pN+ is 60 for shorter, well-differentiated cancers (<2.5 cm) and 20 for longer, poorly differentiated ones. Conclusions In esophageal cancer, pN+, increasing number of positive nodes, and increasing pN classification are associated with deeper invading, longer, and poorly differentiated cancers. Consequently, if the goal of lymphadenectomy is to accurately define pN+ status of such cancers, few nodes need to be removed. Conversely, superficial, shorter, and well-differentiated cancers require a more extensive lymphadenectomy to accurately define pN+ status. PMID:28009736

  14. Role of Neck Dissection in Clinical T3N0M0 Lesion of Oral Cavity: Changing Trend.

    PubMed

    Dass, Arjun; Singhal, Surinder K; Punia, Rps; Gupta, Nitin; Verma, Hitesh; Budhiraja, Shilpi; Salaria, Minakshi

    2017-08-01

    Neck dissection is an important part in the management of head and neck malignancies especially in terms of control of nodal metastasis. The study is focused on evaluating the profile of lymph nodes in T 3 N 0 M 0 lesion of different subsides of oral cavity. To evaluate the utility of neck dissection in T 3 N 0 M 0 stage of carcinomas of the different region of oral cavity. Ninety patients aged 20 to 70 years underwent treatment for carcinoma of the oral cavity at our center between 2005 and 2013. Of these, 39 patients were stage T 3 N 0 M 0 and underwent excision of the primary lesion with neck dissection. The data were collected retrospectively from hospital record library. These patients were evaluated clinically, radiologically and compared with intra operative finding. Addition of radiotherapy was decided on final histopathology. Out of 39 patients, the site of primary tumour in 21 patients was tongue, in 13 patients was Buccal Mucosa (BM), in 2 patients was lip and in 3 patients was Floor of Mouth (FOM) with tongue. In patients with clinically negative neck nodes, ultrasonography and intra-operative examination revealed the presence of suspicious nodes in 35.9% and 30.7% cases respectively. Occult metastasis in the nodes was identified on histopathological examination in 15 patients (38.5%). A total of 14 patients of carcinoma of tongue and one patient of BM showed positive nodes on histopathology. These patients with positive neck nodes on histopathology, were sent for postoperative radiotherapy. At follow up examination, four patients showed local and distal recurrence and they were managed accordingly. Out of 39 patients, 11 patients of BM, 2 patients of lip, 1 patient of FOM and 6 patients of tongue were disease free in last follow up. Selective neck dissection is an effective therapeutic intervention in patients without clinically involved neck nodes. It can upstage the tumour and additional treatment may be advised. In patients with carcinoma of buccal

  15. 6d $$ \\mathcal{N}=\\left(1,\\;0\\right) $$ theories on S 1/T 2 and class S theories: part II

    DOE PAGES

    Ohmori, Kantaro; Shimizu, Hiroyuki; Tachikawa, Yuji; ...

    2015-12-21

    Here, we study the T 2 compactification of a class of 6dmore » $$ \\mathcal{N}=\\left(1,\\;0\\right) $$ theories that is Higgsable to $$ \\mathcal{N}=\\left(2,\\;0\\right) $$ theories. We show that the resulting 4d N=2 theory at the origin of the Coulomb branch and the parameter space is generically given by two superconformal matter sectors coupled by an infrared-free gauge multiplet and another conformal gauge multiplet. Our analysis utilizes the 5d theories obtained by putting the same class of 6d theories on S 1. Our class includes, among others, the 6d theories describing multiple M 5 branes on an ALE singularity, and we analyze them in detail. The resulting 4d theory has manifestly both the SL(2,Z) and the full flavor symmetry. We also discuss in detail the special cases of 6d theories where the infrared-free gauge multiplet is absent. In an appendix, we give a field-theoretical argument for an F-theoretic constraint that forbids a particular 6d anomaly-free matter content, as an application of our analysis.« less

  16. 6d $$ \\mathcal{N}=\\left(1,\\;0\\right) $$ theories on S 1/T 2 and class S theories: part II

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ohmori, Kantaro; Shimizu, Hiroyuki; Tachikawa, Yuji

    Here, we study the T 2 compactification of a class of 6dmore » $$ \\mathcal{N}=\\left(1,\\;0\\right) $$ theories that is Higgsable to $$ \\mathcal{N}=\\left(2,\\;0\\right) $$ theories. We show that the resulting 4d N=2 theory at the origin of the Coulomb branch and the parameter space is generically given by two superconformal matter sectors coupled by an infrared-free gauge multiplet and another conformal gauge multiplet. Our analysis utilizes the 5d theories obtained by putting the same class of 6d theories on S 1. Our class includes, among others, the 6d theories describing multiple M 5 branes on an ALE singularity, and we analyze them in detail. The resulting 4d theory has manifestly both the SL(2,Z) and the full flavor symmetry. We also discuss in detail the special cases of 6d theories where the infrared-free gauge multiplet is absent. In an appendix, we give a field-theoretical argument for an F-theoretic constraint that forbids a particular 6d anomaly-free matter content, as an application of our analysis.« less

  17. High Resolution 13C MRI With Hyperpolarized Urea: In Vivo T2 Mapping and 15N Labeling Effects

    PubMed Central

    Reed, Galen D.; von Morze, Cornelius; Bok, Robert; Koelsch, Bertram L.; Van Criekinge, Mark; Smith, Kenneth J.; Shang, Hong; Larson, Peder E. Z.; Kurhanewicz, John; Vigneron, Daniel B.

    2014-01-01

    13C steady state free precession (SSFP) magnetic resonance imaging and effective spin-spin relaxation time (T2) mapping were performed using hyperpolarized [13C] urea and [13C, 15N2] urea injected intravenously in rats. 15N labeling gave large T2 increases both in solution and in vivo due to the elimination of a strong scalar relaxation pathway. The T2 increase was pronounced in the kidney, with [13C, 15N2] urea giving T2 values of 6.3±1.3 s in the cortex and medulla, and 11±2 s in the renal pelvis. The measured T2 in the aorta was 1.3±0.3 s. [13C] urea showed shortened T2 values in the kidney of 0.23±0.03 s compared to 0.28±0.03 s measured in the aorta. The enhanced T2 of [13C, 15N2] urea was utilized to generate large signal enhancement by SSFP acquisitions with flip angles approaching the fully refocused regime. Projection images at 0.94 mm in-plane resolution were acquired with both urea isotopes, with [13C, 15N2] urea giving a greater than four-fold increase in signal-to-noise ratio [13C] over urea. PMID:24235273

  18. Mortality Among Men with Advanced Prostate Cancer Excluded from the ProtecT Trial.

    PubMed

    Johnston, Thomas J; Shaw, Greg L; Lamb, Alastair D; Parashar, Deepak; Greenberg, David; Xiong, Tengbin; Edwards, Alison L; Gnanapragasam, Vincent; Holding, Peter; Herbert, Phillipa; Davis, Michael; Mizielinsk, Elizabeth; Lane, J Athene; Oxley, Jon; Robinson, Mary; Mason, Malcolm; Staffurth, John; Bollina, Prasad; Catto, James; Doble, Andrew; Doherty, Alan; Gillatt, David; Kockelbergh, Roger; Kynaston, Howard; Prescott, Steve; Paul, Alan; Powell, Philip; Rosario, Derek; Rowe, Edward; Donovan, Jenny L; Hamdy, Freddie C; Neal, David E

    2017-03-01

    Early detection and treatment of asymptomatic men with advanced and high-risk prostate cancer (PCa) may improve survival rates. To determine outcomes for men diagnosed with advanced PCa following prostate-specific antigen (PSA) testing who were excluded from the ProtecT randomised trial. Mortality was compared for 492 men followed up for a median of 7.4 yr to a contemporaneous cohort of men from the UK Anglia Cancer Network (ACN) and with a matched subset from the ACN. PCa-specific and all-cause mortality were compared using Kaplan-Meier analysis and Cox's proportional hazards regression. Of the 492 men excluded from the ProtecT cohort, 37 (8%) had metastases (N1, M0=5, M1=32) and 305 had locally advanced disease (62%). The median PSA was 17μg/l. Treatments included radical prostatectomy (RP; n=54; 11%), radiotherapy (RT; n=245; 50%), androgen deprivation therapy (ADT; n=122; 25%), other treatments (n=11; 2%), and unknown (n=60; 12%). There were 49 PCa-specific deaths (10%), of whom 14 men had received radical treatment (5%); and 129 all-cause deaths (26%). In matched ProtecT and ACN cohorts, 37 (9%) and 64 (16%), respectively, died of PCa, while 89 (22%) and 103 (26%) died of all causes. ProtecT men had a 45% lower risk of death from PCa compared to matched cases (hazard ratio 0.55, 95% confidence interval 0.38-0.83; p=0.0037), but mortality was similar in those treated radically. The nonrandomised design is a limitation. Men with PSA-detected advanced PCa excluded from ProtecT and treated radically had low rates of PCa death at 7.4-yr follow-up. Among men who underwent nonradical treatment, the ProtecT group had a lower rate of PCa death. Early detection through PSA testing, leadtime bias, and group heterogeneity are possible factors in this finding. Prostate cancer that has spread outside the prostate gland without causing symptoms can be detected via prostate-specific antigen testing and treated, leading to low rates of death from this disease. Copyright

  19. Image Quality Assessment of 2D versus 3D T2WI and Evaluation of Ultra-high b-Value (b=2,000 mm/s2) DWI for Response Assessment in Rectal Cancer.

    PubMed

    Hausmann, Daniel; Liu, Jing; Budjan, Johannes; Reichert, Miriam; Ong, Melissa; Meyer, Mathias; Smakic, Arman; Grimm, Robert; Strecker, Ralph; Schoenberg, Stefan O; Wang, Xiaoying; Attenberger, Ulrike I

    2018-02-01

    The purpose of this IRB-approved, retrospective study was to compare image quality between 2D and high-resolution 3D, T2-weighted (T2WI) magnetic resonance imaging (MRI) sequences and to investigate the additional value of ultra-high b-value diffusion-weighted imaging (DWI; b=2,000 mm/s 2 ) for both rectal cancer staging and evaluating treatment response. From 12 February to 24 August 2016, 26 consecutive patients (22 males, four females; mean age: 61.9±14.0 years) with histologically-proven rectal cancer. In total 31 examinations [12 prior to and 19 after chemoradiation (CRT)] were included. The patients underwent pelvic MRI on a 3.0-T scanner (Magnetom Skyra, Erlangen, Germany). Three radiologists (3, 4, and 5 years of experience in MRI, respectively) independently assessed all images and rated the image quality of DWI (b=800 mm/s 2 ), apparent diffusion coefficient map, DWI (b=2,000 mm/s 2 ), 3D sagittal T2WI, 3D axial T2WI, 2D sagittal T2WI, and 2D axial T2WI of each patient, respectively. In addition, signal intensity ratios (SIR) were calculated between rectal cancer and obturator internus muscle (background) in all patients after CRT on DWI (b=2,000 mm/s 2 ) and correlated with histopathological regression grade (RG). Tumor delineation was significantly better by 2D T2WI than 3D T2WI both before and after CRT (before CRT: Z=-3.2, p=0.02; after CRT: Z=-4.408, p<0.001; all: Z=-5.192; p<0.001) and was the preferred method, although image quality ratings were not significantly different (3D sagittal: 4.00±0.48; 2D sagittal: 4.03±0.34, p=0.713; 3D axial: 3.85±0.61, 2D axial: 3.78±0.64, p=0.537). Independent t-test showed significantly higher SIR between those with RG 1 or 2 (moderate response: mean score=2.02) and those with RG 3+4 (good response: mean score=0.8) (t=3.044, p=0.011). In those with RG 4 (complete response), SIR of b2000 was 0.946 compared to a 1.41 average of the whole cohort. In two patients, tumor was invisible on b2000 following CRT (RG 3

  20. Risks on N-acetyltransferase 2 and bladder cancer: a meta-analysis.

    PubMed

    Zhu, Zongheng; Zhang, Jinshan; Jiang, Wei; Zhang, Xianjue; Li, Youkong; Xu, Xiaoming

    2015-01-01

    It is known that bladder cancer disease is closely related to aromatic amine compounds, which could cause cancer by regulating of N-acetylation and N-acetyltransferase 1 and 2 (NAT1 and NAT2). The NAT2 slowed acetylation and would increase the risk of bladder cancer, with tobacco smoke being regarded as a risk factor for this increased risk. However, the relationship between NAT2 slow acetylation and bladder cancer is still debatable at present. This study aims to explore preliminarily correlation of NAT2 slow acetylation and the risk of bladder cancer. The articles were searched from PubMed, Cochran, McGrane English databases, CBM, CNKI, and other databases. The extraction of bladder cancer patients and a control group related with the NAT2 gene were detected by the state, and the referenced articles and publications were also used for data retrieval. Using a random effects model, the model assumes that the studies included in the analysis cases belong to the overall population in the study of random sampling, and considering the variables within and between studies. Data were analyzed using STATA Version 6.0 software, using the META module. According to the inclusion and exclusion criteria of the literature study, 20 independent studies are included in this meta-analysis. The results showed that the individual differences of bladder cancer susceptibility might be part of the metabolism of carcinogens. Slow acetylation status of bladder cancer associated with the pooled odds ratio was 1.31 (95% confidence interval: 1.11-1.55). The status of NAT2 slow N-acetylation is associated with bladder cancer risks, and may increase the risk of bladder cancer.

  1. Patterns of Failure After Radical Cystectomy for pT3-4 Bladder Cancer: Implications for Adjuvant Radiation Therapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Reddy, Abhinav V.; Pariser, Joseph J.; Pearce, Shane M.

    2016-04-01

    Purpose: In patients with muscle-invasive bladder cancer, local-regional failure (LF) has been reported to occur in up to 20% of patients following radical cystectomy. The goals of this study were to describe patterns of LF, as well as assess factors associated with LF in a cohort of patients with pT3-4 bladder cancer. This information may have implications towards the use of adjuvant radiation therapy. Methods and Materials: Patients with pathologic T3-4 N0-1 bladder cancer were examined from an institutional radical cystectomy database. Preoperative demographics and pathologic characteristics were examined. Outcomes included overall survival and LF. Local-regional failures were defined usingmore » follow-up imaging reports and scans, and the locations of LF were characterized. Variables were tested by univariate and multivariate analysis for association with LF and overall survival. Results: A total of 334 patients had pT3-4 and N0-1 disease after radical cystectomy and bilateral pelvic lymph node dissection. Of these, 46% received perioperative chemotherapy. The median age was 71 years old, and median follow-up was 11 months. On univariate analysis, margin status, pT stage, and pN stage, were all associated with LF (P<.05), however, on multivariate analysis, only pT and pN stages were significantly associated with LF (P<.05). Three strata of risk were defined, including low-risk patients with pT3N0 disease, intermediate-risk patients with pT3N1 or pT4N0 disease, and high-risk patients with pT4N1 disease, who had a 2-year incidence of LF of 12%, 33%, and 72%, respectively. The most common sites of pelvic relapse included the external and internal iliac lymph nodes (LNs) and obturator LN regions. Notably, 34% of patients with LF had local-regional only disease at the time of recurrence. Conclusions: Patients with pT4 or N1 disease have a 2-year risk of LF that exceeds 30%. These patients may be the most likely to benefit from local adjuvant therapies.« less

  2. Salvage Surgery after Radiation Failure in T1/T2 Larynx Cancer: Outcomes following Total versus Conservation Surgery.

    PubMed

    Cheraghlou, Shayan; Kuo, Phoebe; Mehra, Saral; Yarbrough, Wendell G; Judson, Benjamin L

    2018-03-01

    Objective After radiation failure for early T-stage larynx cancer, national guidelines recommend salvage surgery. Total laryngectomy and conservation laryngeal surgery with an open or endoscopic approach are both used. Beyond single-institution studies, there is a lack of evidence concerning the outcomes of these procedures. We aim to study whether treatment with conservation laryngeal surgery is associated with poorer outcomes than treatment with total laryngectomy as salvage surgery after radiation failure for T1/T2 larynx cancers. Study Design A retrospective study was conducted of adult squamous cell larynx cancer cases in the National Cancer Database diagnosed from 2004 to 2012. Setting Commission on Cancer cancer programs in the United States. Methods Demographic, facility, tumor, and survival variables were included in the analyses. Multivariate survival regressions as well as univariate Kaplan-Meier analyses were conducted. Results Slightly more than 7% of patients receiving radiotherapy for T1/T2 larynx cancers later received salvage surgery. Salvage with partial laryngectomy was not associated with diminished survival as compared with total laryngectomy. However, positive surgical margins were associated with worse outcomes (hazard ratio, 1.782; P = .001), and a larger percentage of patients receiving partial laryngectomy had positive margins than those receiving total laryngectomy. Facility characteristics were not associated with differences in salvage surgery type or outcomes. Conclusion In recognition of the inherent selection bias, patients who experienced recurrences after radiation for T1/T2 larynx cancer and underwent conservation salvage laryngeal surgery demonstrated clinical outcomes similar to those of patients undergoing salvage total laryngectomy. Increased rates of positive surgical margins were observed among patients undergoing salvage conservation surgery.

  3. Satisfactory surgical outcome of T2 gastric cancer after modified D2 lymphadenectomy.

    PubMed

    Zhang, Shupeng; Wu, Liangliang; Wang, Xiaona; Ding, Xuewei; Liang, Han

    2017-04-01

    Though D2 lymphadenectomy has been increasingly regarded as standard surgical procedure for advanced gastric cancer (GC), the modified D2 (D1 + 7, 8a and 9) lymphadenectomy may be more suitable than D2 dissection for T2 stage GC. The purpose of this study is to elucidate whether the surgical outcome of modified D2 lymphadenectomy was comparable to that of standard D2 dissection in T2 stage GC patients. A retrospective cohort study with 77 cases and 77 controls matched for baseline characteristics was conducted. Patients were categorized into two groups according to the extent of lymphadenectomy: the modified D2 group (mD2) and the standard D2 group (D2). Surgical outcome and recurrence date were compared between the two groups. The 5-year overall survival (OS) rate was 71.4% for patients accepted mD2 lymphadenectomy and 70.1% for those accepted standard D2, respectively, and the difference was not statistically significant. Multivariate survival analysis revealed that curability, tumor size, TNM stage and postoperative complications were independently prognostic factors for T2 stage GC patients. Patients in the mD2 group tended to have less intraoperative blood loss (P=0.001) and shorter operation time (P<0.001) than those in the D2 group. While there were no significant differences in recurrence rate and types, especially lymph node recurrence, between the two groups. The surgical outcome of mD2 lymphadenectomy was equal to that of standard D2, and the use of mD2 instead of standard D2 can be a better option for T2 stage GC.

  4. 3.0T MR imaging of the ankle: Axial traction for morphological cartilage evaluation, quantitative T2 mapping and cartilage diffusion imaging-A preliminary study.

    PubMed

    Jungmann, Pia M; Baum, Thomas; Schaeffeler, Christoph; Sauerschnig, Martin; Brucker, Peter U; Mann, Alexander; Ganter, Carl; Bieri, Oliver; Rummeny, Ernst J; Woertler, Klaus; Bauer, Jan S

    2015-08-01

    To determine the impact of axial traction during high resolution 3.0T MR imaging of the ankle on morphological assessment of articular cartilage and quantitative cartilage imaging parameters. MR images of n=25 asymptomatic ankles were acquired with and without axial traction (6kg). Coronal and sagittal T1-weighted (w) turbo spin echo (TSE) sequences with a driven equilibrium pulse and sagittal fat-saturated intermediate-w (IMfs) TSE sequences were acquired for morphological evaluation on a four-point scale (1=best, 4=worst). For quantitative assessment of cartilage degradation segmentation was performed on 2D multislice-multiecho (MSME) SE T2, steady-state free-precession (SSFP; n=8) T2 and SSFP diffusion-weighted imaging (DWI; n=8) images. Wilcoxon-tests and paired t-tests were used for statistical analysis. With axial traction, joint space width increased significantly and delineation of cartilage surfaces was rated superior (P<0.05). Cartilage surfaces were best visualized on coronal T1-w images (P<0.05). Differences for cartilage matrix evaluation were smaller. Subchondral bone evaluation, motion artifacts and image quality were not significantly different between the acquisition methods (P>0.05). T2 values were lower at the tibia than at the talus (P<0.001). Reproducibility was better for images with axial traction. Axial traction increased the joint space width, allowed for better visualization of cartilage surfaces and improved compartment discrimination and reproducibility of quantitative cartilage parameters. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. Anti-HER2 CD4(+) T-helper type 1 response is a novel immune correlate to pathologic response following neoadjuvant therapy in HER2-positive breast cancer.

    PubMed

    Datta, Jashodeep; Berk, Erik; Xu, Shuwen; Fitzpatrick, Elizabeth; Rosemblit, Cinthia; Lowenfeld, Lea; Goodman, Noah; Lewis, David A; Zhang, Paul J; Fisher, Carla; Roses, Robert E; DeMichele, Angela; Czerniecki, Brian J

    2015-05-23

    A progressive loss of circulating anti-human epidermal growth factor receptor-2/neu (HER2) CD4(+) T-helper type 1 (Th1) immune responses is observed in HER2(pos)-invasive breast cancer (IBC) patients relative to healthy controls. Pathologic complete response (pCR) following neoadjuvant trastuzumab and chemotherapy (T + C) is associated with decreased recurrence and improved prognosis. We examined differences in anti-HER2 Th1 responses between pCR and non-pCR patients to identify modifiable immune correlates to pathologic response following neoadjuvant T + C. Anti-HER2 Th1 responses in 87 HER2(pos)-IBC patients were examined using peripheral blood mononuclear cells pulsed with 6 HER2-derived class II peptides via IFN-γ ELISPOT. Th1 response metrics were anti-HER2 responsivity, repertoire (number of reactive peptides), and cumulative response across 6 peptides (spot-forming cells [SFC]/10(6) cells). Anti-HER2 Th1 responses of non-pCR patients (n = 4) receiving adjuvant HER2-pulsed type 1-polarized dendritic cell (DC1) vaccination were analyzed pre- and post-immunization. Depressed anti-HER2 Th1 responses observed in treatment-naïve HER2(pos)-IBC patients (n = 22) did not improve globally in T + C-treated HER2(pos)-IBC patients (n = 65). Compared with adjuvant T + C receipt, neoadjuvant T + C - utilized in 61.5 % - was associated with higher anti-HER2 Th1 repertoire (p = 0.048). While pCR (n = 16) and non-pCR (n = 24) patients did not differ substantially in demographic/clinical characteristics, pCR patients demonstrated dramatically higher anti-HER2 Th1 responsivity (94 % vs. 33 %, p = 0.0002), repertoire (3.3 vs. 0.3 peptides, p < 0.0001), and cumulative response (148.2 vs. 22.4 SFC/10(6), p < 0.0001) versus non-pCR patients. After controlling for potential confounders, anti-HER2 Th1 responsivity remained independently associated with pathologic response (odds ratio 8.82, p = 0.016). This IFN-γ(+) immune disparity was mediated by anti-HER2 CD4(+)T

  6. Perovskites Bi0.8La0.2FeO3 and Bi0.8La0.2Fe0.95Cr0.05O3: Crystal structure and magnetic and charge states of iron ions

    NASA Astrophysics Data System (ADS)

    Sigov, A. S.; Pokatilov, V. S.; Makarova, A. O.; Pokatilov, V. V.

    2014-06-01

    Perovskites of the Bi0.8La0.2Fe1 - x Cr x O3 system ( x = 0, 0.05) were investigated by Mössbauer spectroscopy in the temperature range of 298-800 K. The samples were fabricated by solid-state synthesis and had a rhombic structure. Iron ions in Bi0.8La0.2FeO3 and Bi0.8La0.2Fe0.95Cr0.05O3 are situated in trivalent states. The magnetic transition temperatures (the Néel temperatures T N ) T N = 677.5 ± 2.5 K for Bi0.8La0.2FeO3 and T N = 647.6 ± 2.5 K for Bi0.8La0.2Fe0.95Cr0.05O3 are measured. The substitution of trivalent iron ions from trivalent chromium ions in the amount x = 0.05 in Bi0.8La0.2Fe0.95Cr0.05O3 perovskite decreases the hyperfine magnetic field at nuclei 57Fe in Fe+3-O-Cr+3 chains by 30 kOe.

  7. Differences in health related quality of life in the randomised ARTSCAN study; accelerated vs. conventional radiotherapy for head and neck cancer. A five year follow up.

    PubMed

    Nyqvist, Johanna; Fransson, Per; Laurell, Göran; Hammerlid, Eva; Kjellén, Elisabeth; Franzén, Lars; Söderström, Karin; Wickart-Johansson, Gun; Friesland, Signe; Sjödin, Helena; Brun, Eva; Ask, Anders; Nilsson, Per; Ekberg, Lars; Björk-Eriksson, Thomas; Nyman, Jan; Lödén, Britta; Lewin, Freddi; Reizenstein, Johan; Lundin, Erik; Zackrisson, Björn

    2016-02-01

    Health related quality of life (HRQoL) was assessed in the randomised, prospective ARTSCAN study comparing conventional radiotherapy (CF) with accelerated radiotherapy (AF) for head and neck cancer. 750 patients with squamous cell carcinoma (of any grade and stage) in the oral cavity, oro-, or hypopharynx or larynx (except T1-2, N0 glottic carcinoma) without distant metastases were randomised to either conventional fractionation (2 Gy/day, 5 days/week in 49 days, total dose 68 Gy) or accelerated fractionation (1.1+2.0 Gy/day, 5 days/week in 35 days, total dose 68 Gy). HRQoL was assessed with EORTC QLQ-C30, QLQ-H&N35 and HADS at baseline, at end of radiotherapy (eRT) and at 3 and 6 months and 1, 2 and 5 years after start of treatment. The AF group reported HRQoL was significantly lower at eRT and at 3 months for most symptoms, scales and functions. Few significant differences were noted between the groups at 6 months and 5 years. Scores related to functional oral intake never reached baseline. In comparison to CF, AF has a stronger adverse effect on HRQoL in the acute phase. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Histogram analysis of apparent diffusion coefficient at 3.0 T in urinary bladder lesions: correlation with pathologic findings.

    PubMed

    Suo, Shi-Teng; Chen, Xiao-Xi; Fan, Yu; Wu, Lian-Ming; Yao, Qiu-Ying; Cao, Meng-Qiu; Liu, Qiang; Xu, Jian-Rong

    2014-08-01

    To investigate the potential value of histogram analysis of apparent diffusion coefficient (ADC) obtained at standard (700 s/mm(2)) and high (1500 s/mm(2)) b values on a 3.0-T scanner in the differentiation of bladder cancer from benign lesions and in assessing bladder tumors of different pathologic T stages and to evaluate the diagnostic performance of ADC-based histogram parameters. In all, 52 patients with bladder lesions, including benign lesions (n = 7) and malignant tumors (n = 45; T1 stage or less, 23; T2 stage, 7; T3 stage, 8; and T4 stage, 7), were retrospectively evaluated. Magnetic resonance examination at 3.0 T and diffusion-weighted imaging were performed. ADC maps were obtained at two b values (b = 700 and 1500 s/mm(2); ie, ADC-700 and ADC-1500). Parameters of histogram analysis included mean, kurtosis, skewness, and entropy. The correlations between these parameters and pathologic results were revealed. Receiver operating characteristic (ROC) curves were generated to determine the diagnostic value of histogram parameters. Significant differences were found in mean ADC-700, mean ADC-1500, skewness ADC-1500, and kurtosis ADC-1500 between bladder cancer and benign lesions (P = .002-.032). There were also significant differences in mean ADC-700, mean ADC-1500, and kurtosis ADC-1500 among bladder tumors of different pathologic T stages (P = .000-.046). No significant differences were observed in other parameters. Mean ADC-1500 and kurtosis ADC-1500 were significantly correlated with T stage, respectively (ρ = -0.614, P < .001; ρ = 0.374, P = .011). ROC analysis showed that the combination of mean ADC-1500 and kurtosis ADC-1500 has the maximal area under the ROC curve (AUC, 0.894; P < .001) in the differentiation of benign lesions and malignant tumors, with a sensitivity of 77.78% and specificity of 100%. AUCs for differentiating low- and high-stage tumors were 0.840 for mean ADC-1500 (P < .001) and 0.696 for kurtosis ADC-1500 (P

  9. Instantons on a non-commutative T4 from twisted (2,0) and little string theories

    NASA Astrophysics Data System (ADS)

    Cheung, Yeuk-Kwan E.; Ganor, Ori J.; Krogh, Morten; Mikhailov, Andrei Yu.

    We show that the moduli space of the (2,0) and little-string theories compactified on T3 with R-symmetry twists is equal to the moduli space of U(1) instantons on a non-commutative T4. The moduli space of U( q) instantons on a non-commutative T4 is obtained from little-string theories of NS5-branes at Aq-1 singularities with twists. A large class of gauge theories with N=4 SUSY in 2+1D and N=2 SUSY in 3+1D are limiting cases of these theories. Hence, the moduli spaces of these gauge theories can be read off from the moduli spaces of instantons on non-commutative tori. We study the phase transitions in these theories and the action of T-duality. On the purely mathematical side, we give a prediction for the moduli space of two U(1) instantons on a non-commutative T4.

  10. Discovery of 4-anilino-N-methylthieno[3,2-d]pyrimidines and 4-anilino-N-methylthieno[2,3-d]pyrimidines as potent apoptosis inducers.

    PubMed

    Kemnitzer, William; Sirisoma, Nilantha; May, Chris; Tseng, Ben; Drewe, John; Cai, Sui Xiong

    2009-07-01

    We report the discovery of N-((benzo[d][1,3]dioxol-5-yl)methyl)-6-phenylthieno[3,2-d]pyrimidin-4-amine (2a) as an apoptosis inducer using our proprietary cell- and caspase-based ASAP HTS assay, and SAR study of HTS hit 2a which led to the discovery of 4-anilino-N-methylthieno[3,2-d]pyrimidines and 4-anilino-N-methylthieno[2,3-d]pyrimidines as potent apoptosis inducers. Compounds 5d and 5e were the most potent with EC(50) values of 0.008 and 0.004microM in T47D human breast cancer cells, respectively. Compound 5d was found to be highly active in the MX-1 breast cancer model. Functionally, compounds 5d and 5e both induced apoptosis through inhibition of tubulin polymerization.

  11. Two variants on T2DM susceptible gene HHEX are associated with CRC risk in a Chinese population.

    PubMed

    Sun, Rui; Liu, Jian-Ping; Gao, Chang; Xiong, Ying-Ying; Li, Min; Wang, Ya-Ping; Su, Yan-Wei; Lin, Mei; Jiang, An-Li; Xiong, Ling-Fan; Xie, Yan; Feng, Jue-Ping

    2016-05-17

    Increasing amounts of evidence has demonstrated that T2DM (Type 2 Diabetes Mellitus) patients have increased susceptibility to CRC (colorectal cancer). As HHEX is a recognized susceptibility gene in T2DM, this work was focused on two SNPs in HHEX, rs1111875 and rs7923837, to study their association with CRC. T2DM patients without CRC (T2DM-only, n=300), T2DM with CRC (T2DM/CRC, n=135), cancer-free controls (Control, n=570), and CRC without T2DM (CRC-only, n=642) cases were enrolled. DNA samples were extracted from the peripheral blood leukocytes of the patients and sequenced by direct sequencing. The χ2 test was used to compare categorical data. We found that in T2DM patients, rs1111875 but not the rs7923837 in HHEX gene was associated with the occurrence of CRC (p= 0.006). for rs1111875, TC/CC patients had an increased risk of CRC (p=0.019, OR=1.592, 95%CI=1.046-2.423). Moreover, our results also indicated that the two variants of HEEX gene could be risk factors for CRC in general population, independent on T2DM (p< 0.001 for rs1111875, p=0.001 for rs7923837). For rs1111875, increased risk of CRC was observed in TC or TC/CC than CC individuals (p<0.001, OR= 1.780, 95%CI= 1.385-2.287; p<0.001, OR= 1.695, 95%CI= 1.335-2.152). For rs7923837, increased CRC risk was observed in AG, GG, and AG/GG than AA individuals (p< 0.001, OR= 1.520, 95%CI= 1.200-1.924; p=0.036, OR= 1.739, 95%CI= 0.989-3.058; p< 0.001, OR= 1.540, 95%CI= 1.225-1.936). This finding highlights the potentially functional alteration with HHEX rs1111875 and rs7923837 polymorphisms may increase CRC susceptibility. Risk effects and the functional impact of these polymorphisms need further validation.

  12. N-acetyltransferase 2 gene polymorphism as a biomarker for susceptibility to bladder cancer in Bangladeshi population.

    PubMed

    Hosen, Md Bayejid; Islam, Jahidul; Salam, Md Abdus; Islam, Md Fakhrul; Hawlader, M Zakir Hossain; Kabir, Yearul

    2015-03-01

    To investigate the association between the three most common single nucleotide polymorphisms of the N-acetyltransferase 2 gene together with cigarette smoking and the risk of developing bladder cancer and its aggressiveness. A case-control study on 102 bladder cancer patients and 140 control subjects was conducted. The genomic DNA was extracted from peripheral white blood cells and N-acetyltransferase 2 alleles were differentiated by polymerase chain reaction-based restriction fragment length polymorphism methods. Bladder cancer risk was estimated as odds ratio and 95% confidence interval using binary logistic regression models adjusting for age and gender. Overall, N-acetyltransferase 2 slow genotypes were associated with bladder cancer risk (odds ratio=4.45; 95% confidence interval=2.26-8.77). The cigarette smokers with slow genotypes were found to have a sixfold increased risk to develop bladder cancer (odds ratio=6.05; 95% confidence interval=2.23-15.82). Patients with slow acetylating genotypes were more prone to develop high-grade (odds ratio=6.63; 95% confidence interval=1.15-38.13; P<0.05) and invasive (odds ratio=10.6; 95% confidence interval=1.00-111.5; P=0.05) tumor. N-acetyltransferase 2 slow genotype together with tobacco smoking increases bladder cancer risk. Patients with N-acetyltransferase 2 slow genotypes were more likely to develop a high-grade and invasive tumor. N-acetyltransferase 2 slow genotype is an important genetic determinant for bladder cancer in Bangladesh population. © 2014 Wiley Publishing Asia Pty Ltd.

  13. Incidental pT2-T3 gallbladder cancer after a cholecystectomy: outcome of staging at 3 months prior to a radical resection

    PubMed Central

    Ausania, Fabio; Tsirlis, Theodoris; White, Steven A; French, Jeremy J; Jaques, Bryon C; Charnley, Richard M; Manas, Derek M

    2013-01-01

    Introduction Patients with incidental pT2-T3 gallbladder cancer (IGC) after a cholecystectomy may benefit from a radical re-resection although their optimal treatment strategy is not well defined. In this Unit, such patients undergo delayed staging at 3 months after a cholecystectomy to assess the evidence of a residual tumour, extra hepatic spread and the biological behaviour of the tumour. The aim of this study was to evaluate the outcome of patients who had delayed staging at 3 months after a cholecystectomy. Methods From July 2003 to July 2011, 56 patients with T2-T3 gallbladder cancer were referred to this Unit of which 49 were diagnosed incidentally on histology after a cholecystectomy. All 49 patients underwent delayed pre-operative staging using multi-detector computed tomography (MDCT) followed selectively by laparoscopy at 3 months after a cholecystectomy. Data were collected from a prospectively held database. The peri-operative and long-term outcomes of patients were analysed. SPSS software was used for statistical analysis. Results There were 38 pT2 and 11 pT3 tumours. After delayed staging, 24/49 (49%) patients underwent a radical resection, 24/49 (49%) were found to be inoperable on pre-operative assessment and 1/49 (2%) patient underwent an exploratory laparotomy and were found to be unresectable. The overall median survival from referral was 20.7 months (54.8 months for the group who had a radical re-resection versus 9.7 months for the group who had unresectable disease, P < 0.001). These results compare favourably with the reported outcome of fast-track management for incidental pT2-T3 gallbladder cancer from other major series in the literature. Conclusion Delayed staging in patients with incidental T2-T3 gallbladder cancer after a cholecystectomy is a useful strategy to select patients who will benefit from a resection and avoid unnecessary major surgery. PMID:23458168

  14. Role of Increased n-acetylaspartate Levels in Cancer

    PubMed Central

    Zand, Behrouz; Previs, Rebecca A.; Zacharias, Niki M.; Rupaimoole, Rajesha; Mitamura, Takashi; Nagaraja, Archana Sidalaghatta; Guindani, Michele; Dalton, Heather J.; Yang, Lifeng; Baddour, Joelle; Achreja, Abhinav; Hu, Wei; Pecot, Chad V.; Ivan, Cristina; Wu, Sherry Y.; McCullough, Christopher R.; Gharpure, Kshipra M.; Shoshan, Einav; Pradeep, Sunila; Mangala, Lingegowda S.; Rodriguez-Aguayo, Cristian; Wang, Ying; Nick, Alpa M.; Davies, Michael A.; Armaiz-Pena, Guillermo; Liu, Jinsong; Lutgendorf, Susan K.; Baggerly, Keith A.; Eli, Menashe Bar; Lopez-Berestein, Gabriel; Nagrath, Deepak; Bhattacharya, Pratip K.

    2016-01-01

    Background: The clinical and biological effects of metabolic alterations in cancer are not fully understood. Methods: In high-grade serous ovarian cancer (HGSOC) samples (n = 101), over 170 metabolites were profiled and compared with normal ovarian tissues (n = 15). To determine NAT8L gene expression across different cancer types, we analyzed the RNA expression of cancer types using RNASeqV2 data available from the open access The Cancer Genome Atlas (TCGA) website (http://www.cbioportal.org/public-portal/). Using NAT8L siRNA, molecular techniques and histological analysis, we determined cancer cell viability, proliferation, apoptosis, and tumor growth in in vitro and in vivo (n = 6–10 mice/group) settings. Data were analyzed with the Student’s t test and Kaplan-Meier analysis. Statistical tests were two-sided. Results: Patients with high levels of tumoral NAA and its biosynthetic enzyme, aspartate N-acetyltransferase (NAT8L), had worse overall survival than patients with low levels of NAA and NAT8L. The overall survival duration of patients with higher-than-median NAA levels (3.6 years) was lower than that of patients with lower-than-median NAA levels (5.1 years, P = .03). High NAT8L gene expression in other cancers (melanoma, renal cell, breast, colon, and uterine cancers) was associated with worse overall survival. NAT8L silencing reduced cancer cell viability (HEYA8: control siRNA 90.61%±2.53, NAT8L siRNA 39.43%±3.00, P < .001; A2780: control siRNA 90.59%±2.53, NAT8L siRNA 7.44%±1.71, P < .001) and proliferation (HEYA8: control siRNA 74.83%±0.92, NAT8L siRNA 55.70%±1.54, P < .001; A2780: control siRNA 50.17%±4.13, NAT8L siRNA 26.52%±3.70, P < .001), which was rescued by addition of NAA. In orthotopic mouse models (ovarian cancer and melanoma), NAT8L silencing reduced tumor growth statistically significantly (A2780: control siRNA 0.52 g±0.15, NAT8L siRNA 0.08 g±0.17, P < .001; HEYA8: control siRNA 0.79 g±0.42, NAT8L siRNA 0.24 g±0.18, P = .008, A

  15. CHEK2 mutations and HNPCC-related colorectal cancer.

    PubMed

    Suchy, Janina; Cybulski, Cezary; Wokołorczyk, Dominika; Oszurek, Oleg; Górski, Bohdan; Debniak, Tadeusz; Jakubowska, Anna; Gronwald, Jacek; Huzarski, Tomasz; Byrski, Tomasz; Dziuba, Ireneusz; Gogacz, Marek; Wiśniowski, Rafał; Wandzel, Piotr; Banaszkiewicz, Zbigniew; Kurzawski, Grzegorz; Kładny, Józef; Narod, Steven A; Lubiński, Jan

    2010-06-15

    Recently, the 1100delC variant of cell cycle checkpoint kinase 2 (CHEK2) has been reported to confer a colorectal cancer risk in hereditary non-polyposis-colorectal cancer (HNPCC) and HNPCC-related families in the Netherlands. To investigate whether CHEK2 mutations confer increased cancer risk in HNPCC and HNPCC-related families in Poland, we genotyped 463 probands from HNPCC and HNPCC-related families, and 5,496 controls for 4 CHEK2 alleles (1100delC, IVS2+1G>A, del5395, I157T). All 463 probands were screened for mutations in the HNPCC-related genes MSH2, MLH1 and MSH6. A positive association was observed for HNPCC-related cancer and the I157T missense CHEK2 mutation (OR = 1.7; p = 0.007), but not for the truncating alleles (OR = 1.0; p = 1.0). The association with the I157T was seen both for the 117 cases who fulfill Amsterdam criteria (OR = 1.9; p = 0.1) and for the 346 cases who do not fulfill the criteria (OR = 1.6; p = 0.03). One hundred forty-five of the 463 families had a mutation in MSH2, MLH1 or MSH6 (MMR-positive families). A positive association between the CHEK2 I157T mutation and HNPCC-related cancer was observed only for MMR-negative cases (OR = 2.1; p = 0.0004), but not for MMR-positive cases (OR = 0.8; p = 0.9). The association with I157T was particularly strong for MMR-negative cases with familial colorectal cancer (2 or more first-degree relatives affected) (OR = 2.5; p < 0.0001). We conclude that the I157T variant of CHEK2 increases the risk of colorectal cancer among MMR-negative, HNPCC/HNPCC-related families in Poland.

  16. Selection of proper candidates with resected pathological stage IIIA-N2 non-small cell lung cancer for postoperative radiotherapy

    PubMed Central

    Hui, Zhouguang; Dai, Honghai; Liang, Jun; Lv, Jima; Zhou, Zongmei; Feng, Qinfu; Xiao, Zefen; Chen, Dongfu; Zhang, Hongxing; Yin, Weibo; Wang, Luhua

    2015-01-01

    Background To establish a prediction model in selecting fit patients with resected pIIIA-N2 non-small cell lung cancer (NSCLC) for postoperative radiotherapy (PORT), and evaluate the model in clinical practice. Methods Between January 2003 and December 2005, 221 patients with resected pIIIA-N2 NSCLC were retrospectively analyzed. The effect of PORT on overall survival (OS) of patients with different clinicopathological factors was evaluated and the results were used to establish a prediction model to select patients fit for PORT. Results Compared with the control, PORT significantly improved the OS of patients with a smoking index ≤400 (P = 0.033), cN2 (P = 0.003), pT3 (P = 0.014), squamous cell carcinoma (SCC) (P = 0.013), or ≥4 positive nodes (P = 0.025). Patients were divided from zero to all five factors into low, middle, and high PORT index (PORT-I) groups (scored 0–1, 2, and 3–5, respectively). PORT did not improve OS (3-year, P = 0.531), disease free survival (DFS) (P = 0.358), or loco-regional recurrence free survival (LRFS) (P = 0.412) in the low PORT-I group. PORT significantly improved OS (P = 0.033), and tended to improve DFS (P = 0.064), but not LRFS (P = 0.287) in the middle PORT-I group. PORT could significantly improve OS (P = 0.000), DFS (P = 0.000), and LRFS (P = 0.006) in the high PORT-I group. Conclusion The prediction model is valuable in selecting patients with resected pIIIA-N2 NSCLC fit for PORT. PORT is strongly recommended for patients with three or more of the five factors of smoking index ≤400, cN2, pT3, SCC, and ≥4 positive nodes. PMID:26273382

  17. Associations of adiponectin and leptin with stage and grade of PSA-detected prostate cancer: the ProtecT study.

    PubMed

    Burton, Anya; Martin, Richard M; Holly, Jeff; Lane, J Athene; Donovan, Jenny L; Hamdy, Freddie C; Neal, David E; Tilling, Kate

    2013-02-01

    Obesity has been associated with an increased risk of advanced and fatal prostate cancer; adipokines may mediate this association. We examined associations of the adipokines leptin and adiponectin with the stage and grade of PSA-detected prostate cancer. We conducted a nested case-control study comparing 311 men with mainly locally advanced (≥T3, N1, or M1 cases) vs. 413 men with localized (T2 & NX-0 & M0 controls) PSA-detected prostate cancer, recruited 2001-2009 from 9 UK regions to the ProtecT study. Associations of body mass index and adipokine levels with prostate cancer stage were determined by conditional logistic regression and with grade (Gleason score ≥7 vs. ≤6) by unconditional logistic regression. Adiponectin was inversely associated with prostate cancer stage in overweight and obese men (OR 0.62; 95 % CI 0.42-0.90; p = 0.01), but not in normal weight men (OR 1.48; 0.77-2.82; p = 0.24) (p for interaction 0.007), or all men (OR 0.86; 0.66-1.11; p = 0.24). There was no compelling evidence of associations between leptin or leptin to adiponectin ratio and prostate cancer stage. No strong associations of adiponectin, leptin, or leptin:adiponectin ratio with grade were seen. This study provides some evidence that adiponectin levels may be associated with prostate cancer stage, dependent on the degree of adiposity of the man. Our results are consistent with adiponectin countering the adverse effects of obesity on prostate cancer progression.

  18. [Study of the supra-glottic pressure during partial constriction of the vocal tract].

    PubMed

    Suares, M; Cayrayre, F; Ouaknine, M; de la Brèteque, B Amy; Giovanni, A

    2004-01-01

    Phonation in a small plastic tube 22 cm length and 5 mms diameter (basic exercise of the method of Dr Amy de la Brèteque), is current practice in vocal rehabilitation in France. This work aims to show the effects of this method on the glottic vibration. The hypothesis was that at the time of phonation in the tube with a strong flow as recommended in the method, the vocal cords vibrate without contact. This limits the mechanical trauma at this level. We have analyzed the sound production in a tube in 11 trained and not trained subjects. We simultaneously collected the intra-oral air pressure and the vocal signal which was subjected to a spectral analysis. Spectral analysis confirmed that the signal was produced correctly i.e. with a strong flow and without interruption of the sound less rich in harmonics. We interpreted these results in the light of our preceding works on the glottic vibration and we show that this vocal production was of the sinusoidal type; this implies the absence of physical contact between the vocal cords, which validates our hypothesis. Further works are necessary to better understand the physical relations between the supra-glottic aerodynamic phenomena and the vibratory functioning of the vocal cords and also to analyze the therapeutic potential ofthe method within speech therapy rehabilitation.

  19. A MicroRNA Signature Associated With Metastasis of T1 Colorectal Cancers to Lymph Nodes.

    PubMed

    Ozawa, Tsuyoshi; Kandimalla, Raju; Gao, Feng; Nozawa, Hiroaki; Hata, Keisuke; Nagata, Hiroshi; Okada, Satoshi; Izumi, Daisuke; Baba, Hideo; Fleshman, James; Wang, Xin; Watanabe, Toshiaki; Goel, Ajay

    2018-03-01

    Most T1 colorectal cancers treated by radical surgery can now be cured by endoscopic submucosal dissection. Although 70%-80% of T1 colorectal cancers are classified as high risk, <16% of these patients actually have lymph node metastases. Biomarkers are needed to identify patients with T1 cancers with the highest risk of metastasis, to prevent unnecessary radical surgery. We collected data from The Cancer Genome Atlas and identified 5 microRNAs (MIR32, MIR181B, MIR193B, MIR195, and MIR411) with significant changes in expression in T1 and T2 colorectal cancers with vs without lymph node metastases. Levels of the 5 microRNAs identified patients with lymph node invasion by T1 or T2 cancers with an area under the receiver operating characteristic curve (AUROC) value of 0.84. We validated these findings in 2 cohorts of patients with T1 cancers, using findings from histology as the reference. The 5-microRNA signature identified T1 cancers with lymph node invasion in cohort 1 with an AUROC value of 0.83, and in cohort 2 with an AUROC value of 0.74. When we analyzed biopsy samples from untreated patients, the 5-microRNA signature identified cancers with lymph node metastases with an AUROC value of 0.77. The 5-microRNA therefore identifies high-risk T1 colorectal cancers with a greater degree of accuracy than currently used pathologic features. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

  20. Texture features on T2-weighted magnetic resonance imaging: new potential biomarkers for prostate cancer aggressiveness

    NASA Astrophysics Data System (ADS)

    Vignati, A.; Mazzetti, S.; Giannini, V.; Russo, F.; Bollito, E.; Porpiglia, F.; Stasi, M.; Regge, D.

    2015-04-01

    To explore contrast (C) and homogeneity (H) gray-level co-occurrence matrix texture features on T2-weighted (T2w) Magnetic Resonance (MR) images and apparent diffusion coefficient (ADC) maps for predicting prostate cancer (PCa) aggressiveness, and to compare them with traditional ADC metrics for differentiating low- from intermediate/high-grade PCas. The local Ethics Committee approved this prospective study of 93 patients (median age, 65 years), who underwent 1.5 T multiparametric endorectal MR imaging before prostatectomy. Clinically significant (volume ≥0.5 ml) peripheral tumours were outlined on histological sections, contoured on T2w and ADC images, and their pathological Gleason Score (pGS) was recorded. C, H, and traditional ADC metrics (mean, median, 10th and 25th percentile) were calculated on the largest lesion slice, and correlated with the pGS through the Spearman correlation coefficient. The area under the receiver operating characteristic curve (AUC) assessed how parameters differentiate pGS = 6 from pGS ≥ 7. The dataset included 49 clinically significant PCas with a balanced distribution of pGS. The Spearman ρ and AUC values on ADC were: -0.489, 0.823 (mean) -0.522, 0.821 (median) -0.569, 0.854 (10th percentile) -0.556, 0.854 (25th percentile) -0.386, 0.871 (C); 0.533, 0.923 (H); while on T2w they were: -0.654, 0.945 (C); 0.645, 0.962 (H). AUC of H on ADC and T2w, and C on T2w were significantly higher than that of the mean ADC (p = 0.05). H and C calculated on T2w images outperform ADC parameters in correlating with pGS and differentiating low- from intermediate/high-risk PCas, supporting the role of T2w MR imaging in assessing PCa biological aggressiveness.

  1. Non-Abelian black string solutions of N = (2,0) , d = 6 supergravity

    NASA Astrophysics Data System (ADS)

    Cano, Pablo A.; Ortín, Tomás; Santoli, Camilla

    2016-12-01

    We show that, when compactified on a circle, N = (2, 0), d = 6 supergravity coupled to 1 tensor multiplet and n V vector multiplets is dual to N = (2 , 0) , d = 6 supergravity coupled to just n T = n V + 1 tensor multiplets and no vector multiplets. Both theories reduce to the same models of N = 2 , d = 5 supergravity coupled to n V 5 = n V + 2 vector fields. We derive Buscher rules that relate solutions of these theories (and of the theory that one obtains by dualizing the 3-form field strength) admitting an isometry. Since the relations between the fields of N = 2 , d = 5 supergravity and those of the 6-dimensional theories are the same with or without gaugings, we construct supersymmetric non-Abelian solutions of the 6-dimensional gauged theories by uplifting the recently found 5-dimensional supersymmetric non-Abelian black-hole solutions. The solutions describe the usual superpositions of strings and waves supplemented by a BPST instanton in the transverse directions, similar to the gauge dyonic string of Duff, Lü and Pope. One of the solutions obtained interpolates smoothly between two AdS3× S3 geometries with different radii.

  2. A new series of oxycarbonate superconductors (Cu{sub 0.5}C{sub 0.5}){sub m}Ba{sub m+1}Ca{sub n-1}Cu{sub n}O{sub 2}({sub m+n})+1

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Takayama-Muromachi, E.; Kawashima, T.; Matsui, Y.

    1994-12-31

    We found a new series of oxycarbonate superconductors in the Ba-Ca-Cu-C-O system under high pressure of 5 GPa. Their ideal formula is (Cu{sub 0.5}C{sub 0.5}){sub m}Ba{sub m+1}Ca{sub n-1}Cu{sub n}O{sub 2}({sub m+n})+1 ((Cu,C)-m(m+1)(n-1)n). Thus far, n=3, 4 members of the m=1 series, (Cu,C)-1223 and (Cu,C)-1234, have been prepared in bulk while n=4, 5 members, (Cu,C)-2334 and (Cu,C)-2345, have been prepared for the m=2 series. (Cu,C)-1223 shows superconductivity below 67 K while T{sub c}`s of other compounds are above 110 K. In particular, (Cu,C)=1234 has the highest T{sub c} of 117 K.

  3. Comparison of non-Gaussian and Gaussian diffusion models of diffusion weighted imaging of rectal cancer at 3.0 T MRI.

    PubMed

    Zhang, Guangwen; Wang, Shuangshuang; Wen, Didi; Zhang, Jing; Wei, Xiaocheng; Ma, Wanling; Zhao, Weiwei; Wang, Mian; Wu, Guosheng; Zhang, Jinsong

    2016-12-09

    Water molecular diffusion in vivo tissue is much more complicated. We aimed to compare non-Gaussian diffusion models of diffusion-weighted imaging (DWI) including intra-voxel incoherent motion (IVIM), stretched-exponential model (SEM) and Gaussian diffusion model at 3.0 T MRI in patients with rectal cancer, and to determine the optimal model for investigating the water diffusion properties and characterization of rectal carcinoma. Fifty-nine consecutive patients with pathologically confirmed rectal adenocarcinoma underwent DWI with 16 b-values at a 3.0 T MRI system. DWI signals were fitted to the mono-exponential and non-Gaussian diffusion models (IVIM-mono, IVIM-bi and SEM) on primary tumor and adjacent normal rectal tissue. Parameters of standard apparent diffusion coefficient (ADC), slow- and fast-ADC, fraction of fast ADC (f), α value and distributed diffusion coefficient (DDC) were generated and compared between the tumor and normal tissues. The SEM exhibited the best fitting results of actual DWI signal in rectal cancer and the normal rectal wall (R 2  = 0.998, 0.999 respectively). The DDC achieved relatively high area under the curve (AUC = 0.980) in differentiating tumor from normal rectal wall. Non-Gaussian diffusion models could assess tissue properties more accurately than the ADC derived Gaussian diffusion model. SEM may be used as a potential optimal model for characterization of rectal cancer.

  4. [A case of gastric cancer with N2 lymph node metastasis and pancreatic invasion effectively treated with docetax-el/S-1 as a neoadjuvant chemotherapy].

    PubMed

    Omori, Keita; Wakabayashi, Kazuhiko; Ishibashi, Yuji; Ito, Yutaka

    2014-08-01

    A 74-year-old man was diagnosed with advanced gastric cancer(cStage III B). Laparotomy showed N2 lymph node metastasis and pancreatic invasion. Radical resection appeared impossible and was thus not performed. Chemotherapy consisting of a combination of S-1(80mg/m 2, 2-week administration and 1-week rest), and docetaxel(40mg/m2day 1)was administered with the expectation of tumor downstaging. A partial response(PR)was obtained after five courses of this regimen in which the primary lesion and lymph node swelling remarkably improved. Total gastrectomy, splenectomy, partial colectomy, and D2 lymph node dissection were then performed. Pathological analysis revealed very few cancer cells in the primary lesion and that the lymph nodes had become scarred and fibrotic. The histological appearance was judged to be grade 2 and the final diagnosis was T1N0H0P0CY0M0, fStage I A, curability A. Currently, more than 6 years and 4 months after the operation, the patient is alive without any evidence of recurrence. Thus, docetaxel/S-1 combination therapy was an effective neoadjuvant chemotherapy for this case of advanced gastric cancer.

  5. Haralick textural features on T2 -weighted MRI are associated with biochemical recurrence following radiotherapy for peripheral zone prostate cancer.

    PubMed

    Gnep, Khémara; Fargeas, Auréline; Gutiérrez-Carvajal, Ricardo E; Commandeur, Frédéric; Mathieu, Romain; Ospina, Juan D; Rolland, Yan; Rohou, Tanguy; Vincendeau, Sébastien; Hatt, Mathieu; Acosta, Oscar; de Crevoisier, Renaud

    2017-01-01

    To explore the association between magnetic resonance imaging (MRI), including Haralick textural features, and biochemical recurrence following prostate cancer radiotherapy. In all, 74 patients with peripheral zone localized prostate adenocarcinoma underwent pretreatment 3.0T MRI before external beam radiotherapy. Median follow-up of 47 months revealed 11 patients with biochemical recurrence. Prostate tumors were segmented on T 2 -weighted sequences (T 2 -w) and contours were propagated onto the coregistered apparent diffusion coefficient (ADC) images. We extracted 140 image features from normalized T 2 -w and ADC images corresponding to first-order (n = 6), gradient-based (n = 4), and second-order Haralick textural features (n = 130). Four geometrical features (tumor diameter, perimeter, area, and volume) were also computed. Correlations between Gleason score and MRI features were assessed. Cox regression analysis and random survival forests (RSF) were performed to assess the association between MRI features and biochemical recurrence. Three T 2 -w and one ADC Haralick textural features were significantly correlated with Gleason score (P < 0.05). Twenty-eight T 2 -w Haralick features and all four geometrical features were significantly associated with biochemical recurrence (P < 0.05). The most relevant features were Haralick features T 2 -w contrast, T 2 -w difference variance, ADC median, along with tumor volume and tumor area (C-index from 0.76 to 0.82; P < 0.05). By combining these most powerful features in an RSF model, the obtained C-index was 0.90. T 2 -w Haralick features appear to be strongly associated with biochemical recurrence following prostate cancer radiotherapy. 3 J. Magn. Reson. Imaging 2017;45:103-117. © 2016 International Society for Magnetic Resonance in Medicine.

  6. Significant Prognostic Factors for Completely Resected pN2 Non-small Cell Lung Cancer without Neoadjuvant Therapy

    PubMed Central

    Nakao, Masayuki; Mun, Mingyon; Nakagawa, Ken; Nishio, Makoto; Ishikawa, Yuichi; Okumura, Sakae

    2015-01-01

    Purpose: To identify prognostic factors for pathologic N2 (pN2) non-small cell lung cancer (NSCLC) treated by surgical resection. Methods: Between 1990 and 2009, 287 patients with pN2 NSCLC underwent curative resection at the Cancer Institute Hospital without preoperative treatment. Results: The 5-year overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) rates were 46%, 55% and 24%, respectively. The median follow-up time was 80 months. Multivariate analysis identified four independent predictors for poor OS: multiple-zone mediastinal lymph node metastasis (hazard ratio [HR], 1.616; p = 0.003); ipsilateral intrapulmonary metastasis (HR, 1.042; p = 0.002); tumor size >30 mm (HR, 1.013; p = 0.002); and clinical stage N1 or N2 (HR, 1.051; p = 0.030). Multivariate analysis identified three independent predictors for poor RFS: multiple-zone mediastinal lymph node metastasis (HR, 1.457; p = 0.011); ipsilateral intrapulmonary metastasis (HR, 1.040; p = 0.002); and tumor size >30 mm (HR, 1.008; p = 0.032). Conclusion: Multiple-zone mediastinal lymph node metastasis, ipsilateral intrapulmonary metastasis, and tumor size >30 mm were common independent prognostic factors of OS, CSS, and RFS in pN2 NSCLC. PMID:25740454

  7. Prognostic significance of metabolic enzyme pyruvate kinase M2 in breast cancer: A meta-analysis.

    PubMed

    Yang, Yiming; Wu, Ke; Liu, Yulin; Shi, Liang; Tao, Kaixiong; Wang, Guobin

    2017-11-01

    Numerous studies have reported that aberrant pyruvate kinase M2 isoform (PKM2) expressed in cancer, indicating that PKM2 plays a critical role in tumor initiation and progression. Nevertheless, its prognostic value in breast cancer tumor is yet contentious. Therefore, we performed this meta-analysis to evaluate the prognostic significance of PKM2 in breast cancer. Eligible relevant literatures were retrieved by searching PubMed, the Cochrane Library, Embase through December 2016. Articles that comparing different PKM2 expression levels in human breast cancer tissues and prognostic significance were included. Software RevMan 5.3 and STATA (Review Manager (RevMan): [Computer program]. Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014. StataCorp. 2011. Stata Statistical Software: Release 12. College Station, TX: StataCorp LP) were applied to analyze the outcomes. Pooled results were presented in hazardous ratios (HRs) of 5-year overall survival (OS), progression-free survival (PFS), and odds ratios (ORs) of clinicopathological features with 95% confidence intervals. Data from 6 involved studies with 895 patients were summarized. Breast cancer patients with high PKM2 had a worse OS (pooled HR = 1.65, 95% CI = 1.31-2.08, P < .001) and PFS (pooled HR = 2.49, 95% CI = 1.84-3.36, P < .00001). High PKM2 expression is related to lymph node metastasis (N1+N2+N3 vs N0, OR = 1.97, 95%CI = 1.39-2.80, P = .0001). The outcome stability was verified via sensitivity analysis. But elevated PKM2 expression was not correlated to tumor stage (T2+T3 vs T1, pooled OR = 0.80, 95% CI = 0.36-1.77, P = .58) and differential grade (G2+G3 vs G1, OR = 2.74, 95%CI = 0.76-9.84, P = .12). No publication bias was found in the included studies for OS (Begg test, P = .260; Egger test, P = .747). High PKM2 expression denotes worse OS and PFS in breast cancer patients, and correlate with the lymph

  8. Adoptive transfer of autologous, HER2-specific, cytotoxic T lymphocytes for the treatment of HER2-overexpressing breast cancer.

    PubMed

    Bernhard, Helga; Neudorfer, Julia; Gebhard, Kerstin; Conrad, Heinke; Hermann, Christine; Nährig, Jörg; Fend, Falko; Weber, Wolfgang; Busch, Dirk H; Peschel, Christian

    2008-02-01

    The human epidermal growth factor receptor 2 (HER2) has been targeted as a breast cancer-associated antigen by immunotherapeutical approaches based on HER2-directed monoclonal antibodies and cancer vaccines. We describe the adoptive transfer of autologous HER2-specific T-lymphocyte clones to a patient with metastatic HER2-overexpressing breast cancer. The HLA/multimer-based monitoring of the transferred T lymphocytes revealed that the T cells rapidly disappeared from the peripheral blood. The imaging studies indicated that the T cells accumulated in the bone marrow (BM) and migrated to the liver, but were unable to penetrate into the solid metastases. The disseminated tumor cells in the BM disappeared after the completion of adoptive T-cell therapy. This study suggests the therapeutic potential for HER2-specific T cells for eliminating disseminated HER2-positive tumor cells and proposes the combination of T cell-based therapies with strategies targeting the tumor stroma to improve T-cell infiltration into solid tumors.

  9. Long-term results of high-dose conformal radiotherapy for patients with medically inoperable T1-3N0 non-small-cell lung cancer: is low incidence of regional failure due to incidental nodal irradiation?

    PubMed

    Chen, Ming; Hayman, James A; Ten Haken, Randall K; Tatro, Daniel; Fernando, Shaneli; Kong, Feng-Ming

    2006-01-01

    To report the results of high-dose conformal irradiation and examine incidental nodal irradiation and nodal failure in patients with inoperable early-stage non-small-cell lung cancer (NSCLC). This analysis included patients with inoperable CT-staged T1-3N0M0 NSCLC treated on our prospective dose-escalation trial. Patients were treated with radiation alone (total dose, 63-102.9 Gy in 2.1-Gy daily fractions) with a three-dimensional conformal technique without intentional nodal irradiation. Bilateral highest mediastinal and upper/lower paratracheal, prevascular and retrotracheal, sub- and para-aortic, subcarinal, paraesophageal, and ipsilateral hilar regions were delineated individually. Nodal failure and doses of incidental irradiation were studied. The potential median follow-up was 104 months. For patients who completed protocol treatment, median survival was 31 months. The actuarial overall survival rate was 86%, 61%, 43%, and 21% and the cause-specific survival rate was 89%, 70%, 53%, and 35% at 1, 2, 3, and 5 years, respectively. Weight loss (p = 0.008) and radiation dose in Gy (p = 0.013) were significantly associated with overall survival. In only 22% and 13% of patients examined did ipsilateral hilar and paratracheal (and subaortic for left-sided tumor) nodal regions receive a dose of > or = 40 Gy, respectively. Less than 10% of all other nodal regions received a dose of > or = 40 Gy. No patients failed initially at nodal sites. Radiation dose is positively associated with overall survival in patients with medically inoperable T1-3N0 NSCLC, though long-term results remain poor. The nodal failure rate is low and does not seem to be due to high-dose incidental irradiation.

  10. Candidate Dosimetric Predictors of Long-Term Swallowing Dysfunction After Oropharyngeal Intensity-Modulated Radiotherapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Schwartz, David L., E-mail: docdls@mdanderson.or; Department of Experimental Diagnostic Imaging, University of Texas M. D. Anderson Cancer Center, Houston, TX; Hutcheson, Katherine

    2010-12-01

    Purpose: To investigate long-term swallowing function in oropharyngeal cancer patients treated with intensity-modulated radiotherapy (IMRT), and to identify novel dose-limiting criteria predictive for dysphagia. Methods and Materials: Thirty-one patients with Stage IV oropharyngeal squamous carcinoma enrolled on a Phase II trial were prospectively evaluated by modified barium swallow studies at baseline, and 6, 12, and 24 months post-IMRT treatment. Candidate dysphagia-associated organs at risk were retrospectively contoured into original treatment plans. Twenty-one (68%) cases were base of tongue and 10 (32%) were tonsil. Stage distribution was T1 (12 patients), T2 (10), T3 (4), T4 (2), and TX (3), and N2more » (24), N3 (5), and NX (2). Median age was 52.8 years (range, 42-78 years). Thirteen patients (42%) received concurrent chemotherapy during IMRT. Thirteen (42%) were former smokers. Mean dose to glottic larynx for the cohort was limited to 18 Gy (range, 6-39 Gy) by matching IMRT to conventional low-neck fields. Results: Dose-volume constraints (V30 < 65% and V35 < 35% for anterior oral cavity and V55 < 80% and V65 < 30% for high superior pharyngeal constrictors) predictive for objective swallowing dysfunction were identified by univariate and multivariate analyses. Aspiration and feeding tube dependence were observed in only 1 patient at 24 months. Conclusions: In the context of glottic laryngeal shielding, we describe candidate oral cavity and superior pharyngeal constrictor organs at risk and dose-volume constraints associated with preserved long-term swallowing function; these constraints are currently undergoing prospective validation. Strict protection of the glottic larynx via beam-split IMRT techniques promises to make chronic aspiration an uncommon outcome.« less

  11. Can IMRT or Brachytherapy Reduce Dysphagia Associated With Chemoradiotherapy of Head and Neck Cancer? The Michigan and Rotterdam Experiences

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Eisbruch, Avraham; Levendag, Peter C.; Feng, Felix Y.

    Purpose: Dysphagia is a major late complication of intensive chemoradiotherapy of head and neck cancer. The initial clinical results of intensity-modulated radiotherapy (IMRT), or brachytherapy, planned specifically to reduce dysphagia are presented. Patients and Methods: Previous research at Michigan University has suggested that the pharyngeal constrictors and glottic and supraglottic larynx are likely structures whose damage by chemo-RT causes dysphagia and aspiration. In a prospective Michigan trial, 36 patients with oropharyngeal (n = 31) or nasopharyngeal (n = 5) cancer underwent chemo-IMRT. IMRT cost functions included sparing noninvolved pharyngeal constrictors and the glottic and supraglottic larynx. After a review ofmore » published studies, the retropharyngeal nodes at risk were defined as the lateral, but not the medial, retropharyngeal nodes, which facilitated sparing of the swallowing structures. In Rotterdam, 77 patients with oropharyngeal cancer were treated with IMRT, three dimensional RT, or conventional RT; also one-half received brachytherapy. The dysphagia endpoints included videofluoroscopy and observer-assessed scores at Michigan and patient-reported quality-of-life instruments in both studies. Results: In both studies, the doses to the upper and middle constrictors correlated highly with the dysphagia endpoints. In addition, doses to the glottic and supraglottic larynx were significant in the Michigan series. In the Rotterdam series, brachytherapy (which reduced the doses to the swallowing structures) was the only significant factor on multivariate analysis. Conclusion: The dose-response relationships for the swallowing structures found in these studies suggest that reducing their doses, using either IMRT aimed at their sparing, or brachytherapy, might achieve clinical gains in dysphagia.« less

  12. 26 CFR 1.103(n)-2T - Private activity bond defined (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...(n)-2T Section 1.103(n)-2T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY....103(n)-2T Private activity bond defined (temporary). Q-1: What is the definition of the term “private activity bond”? A-1: In general, for purposes of §§ 1.103(n)-1T through 1.103(n)-6T, the term “private...

  13. The Use of Cryotherapy for Papilloma and Early Laryngeal Cancers: Long-term Results.

    PubMed

    Benninger, Michael S; Derakhshan, Adeeb; Milstein, Claudio F

    2015-07-01

    Retrospective chart review. To determine the efficacy of adjuvant cryotherapy in the treatment of early glottic cancer and laryngeal papillomatosis. The use of cryotherapy in conjunction with traditional modalities has recently been proposed to improve voice outcomes in patients with early laryngeal cancer as compared to pretreatment conditions. This study investigates its utility in improving oncological outcomes and decreasing recurrences of laryngeal papillomatosis. Patients with either early glottic cancer or laryngeal papillomatosis that received cryotherapy as part of their surgical regimen were investigated. All patients were seen at a large tertiary care center within a 10-year window. Demographic data were collected and all postoperative notes were reviewed. Recurrences of the laryngeal cancer were noted, as was the duration of time between successive papillomatosis operations. The charts of 54 glottic cancer and 29 papillomatosis patients that received cryotherapy were reviewed. One patient from the papillomatosis cohort was excluded from statistical analysis due to lack of follow-up. Overall, 16 (30%) of the laryngeal cancer patient experienced a malignant recurrence. The overall 5-year survival of these patients was 98% and the 5-year disease-free survival was 74%. The use of adjuvant cryotherapy in the treatment of laryngeal papillomatosis extended the duration of time between surgeries by an average of 79 days (P=.23). The use of adjuvant cryotherapy in the treatment of early glottic cancer does not improve the rate of carcinoma recurrences. Additionally, cryotherapy does not result in a statistically significant increase in the duration of disease-free period for laryngeal papillomatosis patients, although the observed increase may be clinically important. © The Author(s) 2015.

  14. Design, development of water tank-type lung phantom and dosimetric verification in institutions participating in a phase I study of stereotactic body radiation therapy in patients with T2N0M0 non-small cell lung cancer: Japan Clinical Oncology Group trial (JCOG0702).

    PubMed

    Nishio, Teiji; Shirato, Hiroki; Ishikawa, Masayori; Miyabe, Yuki; Kito, Satoshi; Narita, Yuichirou; Onimaru, Rikiya; Ishikura, Satoshi; Ito, Yoshinori; Hiraoka, Masahiro

    2014-05-01

    A domestic multicenter phase I study of stereotactic body radiotherapy (SBRT) for T2N0M0 non-small cell lung cancer in inoperable patients or elderly patients who refused surgery was initiated as the Japan Clinical Oncology Group trial (JCOG0702) in Japan. Prior to the clinical study, the accuracy of dose calculation in radiation treatment-planning systems was surveyed in participating institutions, and differences in the irradiating dose between the institutions were investigated. We developed a water tank-type lung phantom appropriate for verification of the exposure dose in lung SBRT. Using this water tank-type lung phantom, the dose calculated in the radiation treatment-planning system and the measured dose using a free air ionization chamber and dosimetric film were compared in a visiting survey of the seven institutions participating in the clinical study. In all participating institutions, differences between the calculated and the measured dose in the irradiation plan were as follows: the accuracy of the absolute dose in the center of the simulated tumor measured using a free air ionization chamber was within 2%, the mean gamma value was ≤ 0.47 on gamma analysis following the local dose criteria, and the pass rate was >87% for 3%/3 mm from measurement of dose distribution with dosimetric film. These findings confirmed the accuracy of delivery doses in the institutions participating in the clinical study, so that a study with integration of the institutions could be initiated.

  15. Acute Toxicity Profile and Compliance to Accelerated Radiotherapy Plus Carbogen and Nicotinamide for Clinical Stage T2-4 Laryngeal Cancer: Results of a Phase III Randomized Trial

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Janssens, Geert O., E-mail: g.janssens@rther.umcn.nl; Terhaard, Chris H.; Doornaert, Patricia A.

    2012-02-01

    Purpose: To report the acute toxicity profile and compliance from a randomized Phase III trial comparing accelerated radiotherapy (AR) with accelerated radiotherapy plus carbogen and nicotinamide (ARCON) in laryngeal cancer. Methods and Materials: From April 2001 to February 2008, 345 patients with cT2-4 squamous cell laryngeal cancer were randomized to AR (n = 174) and ARCON (n = 171). Acute toxicity was scored weekly until Week 8 and every 2-4 weeks thereafter. Compliance to carbogen and nicotinamide was reported. Results: Between both treatment arms (AR vs. ARCON) no statistically significant difference was observed for incidence of acute skin reactions (moistmore » desquamation: 56% vs. 58%, p = 0.80), acute mucosal reactions (confluent mucositis: 79% vs. 85%, p = 0.14), and symptoms related to acute mucositis (severe pain on swallowing: 53% vs. 58%, p = 0.37; nasogastric tube feeding: 28% vs. 28%, p = 0.98; narcotic medicines required: 58% vs. 58%, p = 0.97). There was a statistically significant difference in median duration of confluent mucositis in favor of AR (2.0 vs 3.0 weeks, p = 0.01). There was full compliance with carbogen breathing and nicotinamide in 86% and 80% of the patients, with discontinuation in 6% and 12%, respectively. Adjustment of antiemesis prophylaxis was needed in 42% of patients. Conclusion: With the exception of a slight increase in median duration of acute confluent mucositis, the present data reveal a similar acute toxicity profile between both regimens and a good compliance with ARCON for clinical stage T2-4 laryngeal cancers. Treatment outcome and late morbidity will determine the real therapeutic benefit.« less

  16. The N2 paradox: similar outcomes of pre- and postoperatively identified single-zone N2a positive non-small-cell lung cancer.

    PubMed

    Tsitsias, Thomas; Boulemden, Anas; Ang, Keng; Nakas, Apostolos; Waller, David A

    2014-05-01

    Resection of N2a non-small-cell lung cancer (NSCLC) diagnosed preoperatively is controversial but there is support for resection of unexpected N2 disease discovered at surgery. Since the seventh TNM edition, we have intentionally resected clinical N2a disease. To validate this policy, we determined prognostic factors associated with all resected N2 disease. From a prospective database of 1131 consecutive patients undergoing elective resection for primary lung cancer over a period of 8 years, we identified 68 patients (35 females (51.4%), mean age 66 years, standard deviation (SD) 9 years) who had pathological N2 disease. All patients had positron emission computed tomography (CT-PET) staging and selective mediastinoscopy. A Cox-regression analysis was performed to identify prognostic factors. At a median follow-up of 38.7 months (standard error 10, 95% confidence interval (CI) 19.0-58.4), the overall median survival was 22.2 months (95% CI 14.6-29.8) with 1-, 2- and 5-year survival rates of 63.3, 46.6 and 13.2%, respectively. Survival after resection of pN2 disease is adversely affected by the need for pneumonectomy, multizone pN2b involvement and by non-compliance with adjuvant chemotherapy. Pathological involvement of the subcarinal zone but no other zone appears to be associated with an adverse prognosis (hazard ratio (HR) 1.87, P = 0.063). Importantly, long-term survival is not different between those patients who have a negative preoperative PET-CT scan and yet are found to have pN2 after resection, and those who are single-zone cN2a positive before resection on PET-CT scan (HR 1.37, P = 0.335). Our results support a policy of intentionally resecting single-zone N2a NSCLC identified preoperatively as part of a multimodality therapy.

  17. T2-weighted signal intensity-selected volumetry for prediction of pathological complete response after preoperative chemoradiotherapy in locally advanced rectal cancer.

    PubMed

    Kim, Sungwon; Han, Kyunghwa; Seo, Nieun; Kim, Hye Jin; Kim, Myeong-Jin; Koom, Woong Sub; Ahn, Joong Bae; Lim, Joon Seok

    2018-06-01

    To evaluate the diagnostic value of signal intensity (SI)-selected volumetry findings in T2-weighted magnetic resonance imaging (MRI) as a potential biomarker for predicting pathological complete response (pCR) to preoperative chemoradiotherapy (CRT) in patients with rectal cancer. Forty consecutive patients with pCR after preoperative CRT were compared with 80 age- and sex-matched non-pCR patients in a case-control study. SI-selected tumor volume was measured on post-CRT T2-weighted MRI, which included voxels of the treated tumor exceeding the SI (obturator internus muscle SI + [ischiorectal fossa fat SI - obturator internus muscle SI] × 0.2). Three blinded readers independently rated five-point pCR confidence scores and compared the diagnostic outcome with SI-selected volumetry findings. The SI-selected volumetry protocol was validated in 30 additional rectal cancer patients. The area under the receiver-operating characteristic curve (AUC) of SI-selected volumetry for pCR prediction was 0.831, with an optimal cutoff value of 649.6 mm 3 (sensitivity 0.850, specificity 0.725). The AUC of the SI-selected tumor volume was significantly greater than the pooled AUC of readers (0.707, p < 0.001). At this cutoff, the validation trial yielded an accuracy of 0.87. SI-selected volumetry in post-CRT T2-weighted MRI can help predict pCR after preoperative CRT in patients with rectal cancer. • Fibrosis and viable tumor MRI signal intensities (SIs) are difficult to distinguish. • T2 SI-selected volumetry yields high diagnostic performance for assessing pathological complete response. • T2 SI-selected volumetry is significantly more accurate than readers and non-SI-selected volumetry. • Post-chemoradiation therapy T2-weighted MRI SI-selected volumetry facilitates prediction of pathological complete response.

  18. Office-Based Autologous Fat Injection Laryngoplasty for Glottic Insufficiency in Patients Under 50 Years Old.

    PubMed

    Hu, Hao-Chun; Hung, Yi-Ting; Lin, Shu-Yi; Tung, Tao-Hsin; Chang, Shyue-Yih

    2018-04-17

    We sought to determine the outcomes of office-based autologous fat injection laryngoplasty in the treatment of patients under 50 years old with glottic insufficiency but without neurological problems or acquired organic lesions in the vocal fold. We conducted a retrospective chart review of consecutive patients under 50 years of age who underwent office-based autologous fat injection laryngoplasty for glottic insufficiency. None of the patients presented neurological problems or acquired organic lesions in the vocal fold. Videolaryngostroboscopic data, objective voice assessment, perceptual measurements of vocal quality, and subjective ratings of voice quality were evaluated before and after treatment. The 23 patients (7 men and 16 women) in this study presented significant improvements in phonatory function in terms of maximum phonation time, jitter, grade, asthenia, and Voice Handicap Index-10 (VHI-10) values at 3 months. Significant improvements in terms of jitter, noise-to-harmonic ratio, grade, roughness, breathiness, asthenia, and the VHI-10 values were also observed at 6 months. Glottic insufficiency in younger patients without neurological problems or acquired organic lesions in the vocal fold can be treated effectively using office-based autologous fat injection laryngoplasty. Significant improvements in phonatory function were observed even 6 months after surgery. Copyright © 2018 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  19. Patterns and Predictors of Early Biochemical Recurrence After Radical Prostatectomy and Adjuvant Radiation Therapy in Men With pT{sub 3}N{sub 0} Prostate Cancer: Implications for Multimodal Therapies

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Briganti, Alberto, E-mail: briganti.alberto@hsr.it; Joniau, Steven; Gandaglia, Giorgio

    Purpose: The aim of our study was to evaluate patterns and predictors of early biochemical recurrence (eBCR) after radical prostatectomy (RP) and adjuvant radiation therapy (aRT) in order to identify which individuals might benefit from additional treatments. Methods and Materials: We evaluated 390 patients with pT{sub 3}N{sub 0} prostate cancer (PCa) receiving RP and aRT at 6 European centers between 1993 and 2006. Patients who were free from BCR at <2 years' follow-up were excluded. This resulted in 374 assessable patients. Early BCR was defined as 2 consecutive prostate-specific antigen (PSA) test values >0.2 ng/mL within 2 or 3 yearsmore » after aRT. Uni- and multivariable Cox regression analyses predicting overall and eBCR after aRT were fitted. Covariates consisted of preoperative PSA results, surgical margins, pathological stage, Gleason score, and aRT dose. Results: Overall, 5- and 8-year BCR-free survival rates were 77.1% and 70.8%, respectively. At a median follow-up of 86 months after aRT, 33 (8.8%) and 55 (14.6%) men experienced BCR within 2 or 3 years after aRT, respectively. In multivariable analyses, Gleason scores of 8 to 10 represented the only independent predictor of eBCR after aRT (all, P≤.01). The risk of BCR was significantly higher in patients with a Gleason score of 8 to 10 disease than in those with Gleason 2 to 6 within 24 months after treatment, after adjusting for all covariates (all, P≤.04). However, given a 24-month BCR free period, the risk of subsequent BCR for men with poorly differentiated disease was equal to that of men with less aggressive disease (all, P≥.3). Conclusions: High Gleason score represents the only predictor of eBCR after RP and aRT in patients affected by pT{sub 3}N{sub 0} PCa. Given the association between early PSA recurrence, clinical progression, and mortality, these patients might be considered candidates for adjuvant medical therapy and/or prophylactic whole-pelvis radiation therapy in addition to a

  20. Final report on the torque key komparison CCM.T-K1.2 measurand torque: 0 N.m, 500 N.m, 1000 N.m

    NASA Astrophysics Data System (ADS)

    Röske, Dirk

    2015-01-01

    The purpose of the CIPM subsequent bilateral comparison CCM.T-K1.2 was to link another participant, namely the National Institute of Metrology (Thailand), in short NIMT, to the CCM.T-K1 torque key comparison. The measuring capabilities up to 1000 N.m of dead-weight torque standard machines with supported lever were investigated. The pilot laboratory was the same in both comparisons—it was the Physikalisch-Technische Bundesanstalt (PTB, Braunschweig, Germany). The same two very stable torque transducers with well-known properties were used as travelling standards. The measurements at the participating laboratory were carried out between November 2007 and February 2008. According to the technical protocol, torque steps of 500 N.m and 1000 N.m had to be measured both in clockwise and anticlockwise directions. Corrections had to be applied to the results reported by the participants taking into account the use of different amplifiers, the creep (due to different loading times of the machines) and the environmental conditions in the laboratories (temperature and relative humidity of the ambient air). The results of the pilot laboratory in this bilateral comparison are in very good agreement with the same results obtained in the CCM.T-K1 comparison. For each of the transducers, the two torque steps and both senses of direction of the torque vector, the key comparison reference value of the CCM.T-K1 was taken, and the results of participant NIMT were calculated with respect to these values. The agreement between the results is very good. The smallest expanded (k = 2) relative uncertainty of the machine stated by the participant is 1 × 10-4. The results of the comparison support this uncertainty statement. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by CCM, according

  1. Association of CYP2D6*10 (c.100C>T) polymorphisms with clinical outcome of breast cancer after tamoxifen adjuvant endocrine therapy in Chinese population.

    PubMed

    Lei, Lei; Wang, Xian; Wu, Xiao-Dan; Wang, Zeng; Chen, Zhan-Hong; Zheng, Ya-Bin; Wang, Xiao-Jia

    2016-01-01

    Tamoxifen is the most widely used adjuvant endocrine therapy for breast cancer. However, the pharmacogenetic effect of CYP2D6 on its efficacy remains unclear. Therefore, this study aimed to evaluate the association of CYP2D6*10 (c.100C>T) polymorphisms with clinical outcome in Chinese breast cancer patients. A total of 72 tamoxifen-treated early breast cancer patients were included in this study. CYP2D6*10 (c.100C>T) polymorphisms (C/C: wild type; T/T: homozygous mutant genotype T; C/T: heterozygote genotype C) were detected by pyrosequencing. The plasma concentrations of tamoxifen and its two major active metabolites were determined by liquid chromatography tandem mass spectrometry (LC-MS). Disease-free survival (DFS) and overall survival (OS) were assessed by Kaplan-Meier analysis, while the Cox proportional hazards model was used in multivariate tests for prognostic significance. We found that T/T carrier showed the lowest serum concentration of endoxifen as compared to C/C and C/T carriers (p<0.01). In the subgroup of patients below 40 years of age, T/T carriers appeared to have the shortest DFS and OS as compared to other genotype carriers (p<0.01). When genotypes (C/C, C/T and T/T carriers) and other clinical characteristics were adjusted, tumor size (>2 cm) and grades were independent prognostic factors for DFS but not OS (tumor size >2 cm: HR: 3.870, 95% CI: 1.045-14.330, P = 0.043; tumor grades: HR: 2.230, 95% CI: 1.090-4.562, P = 0.028). In conclusion, the T/T genotype is a negative prognostic factor in young breast cancer patients using tamoxifen. Tumor size (>2 cm) and grades are independent prognostic factors for DFS, when genotype of CYP2D6*10 (c.100C>T) is adjusted.

  2. Validity of the FACT-H&N (v 4.0) among Malaysian oral cancer patients.

    PubMed

    Doss, J G; Thomson, W M; Drummond, B K; Raja Latifah, R J

    2011-07-01

    To assess the cross-sectional construct validity of the Malay-translated and cross-culturally adapted FACT-H&N (v 4.0) for discriminative use in a sample of Malaysian oral cancer patients. A cross-sectional study of adults newly diagnosed with oral cancer. HRQOL data were collected using the FACT-H&N (v 4.0), a global question and a supplementary set of eight questions ('MAQ') obtained earlier in pilot work. Of the 76 participants (61.8% female; 23.7% younger than 50), most (96.1%) had oral squamous cell carcinoma; two-thirds were in Stages III or IV. At baseline, patients' mean FACT summary (FACT-G, FACT-H&N, FACT-H&N TOI, and FHNSI) and subscale (pwb, swb, ewb, fwb, and hnsc) scores were towards the higher end of the range. Equal proportions (36.8%) rated their overall HRQOL as 'good' or 'average'; fewer than one-quarter rated it as 'poor', and only two as 'very good'. All six FACT summary and most subscales had moderate-to-good internal consistency. For all summary scales, those with 'very poor/poor' self-rated HRQOL differed significantly from the 'good/very good' group. All FACT summary scales correlated strongly (r>0.75). Summary scales showed convergent validity (r>0.90) but little discriminant validity. The discriminant validity of the FHNSI improved with the addition of the MAQ. The FACT-H&N summary scales and most subscales demonstrated acceptable cross-sectional construct validity, reliability and discriminative ability, and thus appear appropriate for further use among Malaysian oral cancer patients. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Rescue of Tolerant CD8+ T Cells during Cancer Immunotherapy with IL2:Antibody Complexes.

    PubMed

    Klevorn, Lauryn E; Berrien-Elliott, Melissa M; Yuan, Jinyun; Kuehm, Lindsey M; Felock, Gregory D; Crowe, Sean A; Teague, Ryan M

    2016-12-01

    Interleukin-2 (IL2) was among the earliest reagents used for cancer immunotherapy due to its ability to support the survival and function of tumor-reactive T cells. However, treatment with IL2 is accompanied by off-target toxicity and low response rates in patients. In mouse models, these issues are largely overcome when IL2 is administered as a cytokine/antibody complex (IL2c). The complex has a longer serum half-life and can be designed for preferential cytokine delivery to specific cells of interest. Early studies showed IL2c could boost antitumor immunity in mice by activating tumor-reactive CD8 + T cells. But such functional T cells are often limited in the tumor microenvironment, where instead unresponsive tolerant T cells are eventually eliminated by apoptosis, representing a major obstacle to the success of cancer immunotherapy. We found that IL2c treatment rescued tumor-specific CD8 + T cells from a state of established tolerance, providing effective immunotherapy in tumor-bearing mice. Expression of the transcription factor T-bet was necessary to drive intratumoral IFNγ production and effector activity by T cells rescued with IL2c. Furthermore, IL2c promoted T-bet expression in human CD4 + and CD8 + T cells in humanized tumor-bearing mice, but also increased the frequency of Foxp3 + regulatory T cells. Our study reveals a novel role for IL2c as a powerful immunotherapeutic reagent capable of reversing tolerance in tumor-reactive T cells, and provides the first evidence that IL2c influences human T cells in vivo, highlighting the translational potential to modulate human antitumor immune responses. Cancer Immunol Res; 4(12); 1016-26. ©2016 AACR. ©2016 American Association for Cancer Research.

  4. Targeting Alpha-Fetoprotein (AFP)-MHC Complex with CAR T-Cell Therapy for Liver Cancer.

    PubMed

    Liu, Hong; Xu, Yiyang; Xiang, Jingyi; Long, Li; Green, Shon; Yang, Zhiyuan; Zimdahl, Bryan; Lu, Jingwei; Cheng, Neal; Horan, Lucas H; Liu, Bin; Yan, Su; Wang, Pei; Diaz, Juan; Jin, Lu; Nakano, Yoko; Morales, Javier F; Zhang, Pengbo; Liu, Lian-Xing; Staley, Binnaz K; Priceman, Saul J; Brown, Christine E; Forman, Stephen J; Chan, Vivien W; Liu, Cheng

    2017-01-15

    The majority of tumor-specific antigens are intracellular and/or secreted and therefore inaccessible by conventional chimeric antigen receptor (CAR) T-cell therapy. Given that all intracellular/secreted proteins are processed into peptides and presented by class I MHC on the surface of tumor cells, we used alpha-fetoprotein (AFP), a specific liver cancer marker, as an example to determine whether peptide-MHC complexes can be targets for CAR T-cell therapy against solid tumors. We generated a fully human chimeric antigen receptor, ET1402L1-CAR (AFP-CAR), with exquisite selectivity and specificity for the AFP 158-166 peptide complexed with human leukocyte antigen (HLA)-A*02:01. We report that T cells expressing AFP-CAR selectively degranulated, released cytokines, and lysed liver cancer cells that were HLA-A*02:01 + /AFP + while sparing cells from multiple tissue types that were negative for either expressed proteins. In vivo, intratumoral injection of AFP-CAR T cells significantly regressed both Hep G2 and AFP 158 -expressing SK-HEP-1 tumors in SCID-Beige mice (n = 8 for each). Moreover, intravenous administration of AFP-CAR T cells in Hep G2 tumor-bearing NSG mice lead to rapid and profound tumor growth inhibition (n = 6). Finally, in an established intraperitoneal liver cancer xenograft model, AFP-CAR T cells showed robust antitumor activity (n = 6). This study demonstrates that CAR T-cell immunotherapy targeting intracellular/secreted solid tumor antigens can elicit a potent antitumor response. Our approach expands the spectrum of antigens available for redirected T-cell therapy against solid malignancies and offers a promising new avenue for liver cancer immunotherapy. Clin Cancer Res; 23(2); 478-88. ©2016 AACR. ©2016 American Association for Cancer Research.

  5. Targeting Sirna Missiles to Her2+ Breast Cancer

    DTIC Science & Technology

    2008-06-01

    intact and appears to be protected from serum nucleases (Fig. 1) . T7 -transcribed siRNA induces higher breast cancer cell cytotoxicity than synthetic...cytotoxicity of T7 transcribed vs s y n t h e t i c anti-HER2 siRNA on HER2+ cells. We acquired a 21 nucleotide (nt) s y n t h e t i c anti-HER2...ErbB2) siRNA and also produced a T7 -transcribed molecule (Silencer Principal Investigator: Medina-Kauwe, Lali K. 2 siRNA construction kit; Ambion) using

  6. Utility of PET-CT in detecting nodal metastasis in cN0 early stage oral cavity squamous cell carcinoma.

    PubMed

    Zhang, Han; Seikaly, Hadi; Biron, Vincent L; Jeffery, Caroline C

    2018-05-01

    Management of the clinically node-negative neck (cN0) in patients with early stage oral cavity squamous cell carcinoma (OCSCC) is challenging. Accurate imaging alternatives to elective neck dissections would help reduce surgical morbidity. While pooled studies suggest that imaging modalities have similar accuracy in predicting occult nodal disease, no study has examined the utility of PET-CT in this specific population of low-volume, clinically T1 and T2 OCSCC patients. A retrospective review of patients in the Alberta Cancer Registry who were diagnosed with cT1 or T2N0M0 OCSCC who underwent elective unilateral or bilateral neck dissections was performed. Pre-operative PET-CT and CT necks were reviewed for number of radiographically suspicious lymph nodes. Surgical pathology reports were reviewed to obtain the total number of nodes sampled and number of malignant nodes. Between 2009 and 2013, 148 patients were diagnosed with cT1 or T2N0M0 OCSCC. Of these, 96 patients underwent elective neck dissections. All patients underwent preoperative CT of the neck with 32 patients having undergone additional preoperative PET-CT. Based on finally surgical pathology, the overall rate of occult metastasis was 13.5% (13/96). The overall sensitivity and specificity of PET-CT in this cohort was 21.4% and 98.4%, respectively with a negative predictive value of 99.1%. Although sensitivity improved in patients with tumors ≥2 cm and depth ≥4 mm, specificity remained unchanged. In patients with cT1 and T2N0 OCSCC, PET-CT has high negative predictive value. These patients can be considered for treatment with single modality surgical resection and elective neck dissection. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. Quantitative Mapping of Human Cartilage at 3.0T

    PubMed Central

    Wang, Ligong; Regatte, Ravinder R.

    2014-01-01

    Rationale and Objectives The objectives of this study were to measure the parallel changes of transverse relaxation times (T2), spin-lattice relaxation time in the rotating frame (T1ρ), and the delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC)-T1 mapping of human knee cartilage in detecting cartilage degeneration at 3.0T. Materials and Methods Healthy volunteers (n = 10, mean age 35.6 years) and patients (n = 10, mean age 65 years) with early knee osteoarthritis (OA) were scanned at 3.0T MR using an 8-channel phased array knee coil (transmit–receive). Quantitative assessment of T2, T1ρ, and dGEMRIC-T1 values (global and regional) were correlated between asymptomatic subjects and patients with OA. Results The average T2 (39 ± 2 milliseconds [mean ± standard deviation] vs. 47 ± 6 milliseconds, P < .0007) and T1ρ (48 ± 3 vs. 62 ± 8 milliseconds, P < .0002) values were all markedly increased in all patients with OA when compared to healthy volunteers. The average dGEMRIC-T1 (1244 ± 134 vs. 643 ± 227 milliseconds, P < .000002) value was sharply decreased after intravenous administration of gadolinium contrast agent in all patients with OA. Conclusions The research results showed that all the T2, T1ρ, and dGEMRIC-T1 relaxation times varied with the cartilage degeneration. The dGEMRIC-T1 and T1ρ relaxation times seem to be more sensitive than T2 in detecting early cartilage degeneration. The preliminary study demonstrated that the early biochemical changes in knee osteoarthritic patients could be detected noninvasively in in vivo using T1ρ and dGEMRIC-T1 mapping. PMID:24594416

  8. PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS

    PubMed Central

    Southey, Melissa C; Goldgar, David E; Winqvist, Robert; Pylkäs, Katri; Couch, Fergus; Tischkowitz, Marc; Foulkes, William D; Dennis, Joe; Michailidou, Kyriaki; van Rensburg, Elizabeth J; Heikkinen, Tuomas; Nevanlinna, Heli; Hopper, John L; Dörk, Thilo; Claes, Kathleen BM; Reis-Filho, Jorge; Teo, Zhi Ling; Radice, Paolo; Catucci, Irene; Peterlongo, Paolo; Tsimiklis, Helen; Odefrey, Fabrice A; Dowty, James G; Schmidt, Marjanka K; Broeks, Annegien; Hogervorst, Frans B; Verhoef, Senno; Carpenter, Jane; Clarke, Christine; Scott, Rodney J; Fasching, Peter A; Haeberle, Lothar; Ekici, Arif B; Beckmann, Matthias W; Peto, Julian; dos-Santos-Silva, Isabel; Fletcher, Olivia; Johnson, Nichola; Bolla, Manjeet K; Sawyer, Elinor J; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Marme, Federik; Burwinkel, Barbara; Yang, Rongxi; Guénel, Pascal; Truong, Thérèse; Menegaux, Florence; Sanchez, Marie; Bojesen, Stig; Nielsen, Sune F; Flyger, Henrik; Benitez, Javier; Zamora, M Pilar; Perez, Jose Ignacio Arias; Menéndez, Primitiva; Anton-Culver, Hoda; Neuhausen, Susan; Ziogas, Argyrios; Clarke, Christina A; Brenner, Hermann; Arndt, Volker; Stegmaier, Christa; Brauch, Hiltrud; Brüning, Thomas; Ko, Yon-Dschun; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Bogdanova, Natalia V; Antonenkova, Natalia N; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Spurdle, Amanda B; Investigators, kConFab; Wauters, Els; Smeets, Dominiek; Beuselinck, Benoit; Floris, Giuseppe; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Olson, Janet E; Vachon, Celine; Pankratz, Vernon S; McLean, Catriona; Haiman, Christopher A; Henderson, Brian E; Schumacher, Fredrick; Le Marchand, Loic; Kristensen, Vessela; Alnæs, Grethe Grenaker; Zheng, Wei; Hunter, David J; Lindstrom, Sara; Hankinson, Susan E; Kraft, Peter; Andrulis, Irene; Knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Jukkola-Vuorinen, Arja; Grip, Mervi; Kauppila, Saila; Devilee, Peter; Tollenaar, Robert A E M; Seynaeve, Caroline; Hollestelle, Antoinette; Garcia-Closas, Montserrat; Figueroa, Jonine; Chanock, Stephen J; Lissowska, Jolanta; Czene, Kamila; Darabi, Hatef; Eriksson, Mikael; Eccles, Diana M; Rafiq, Sajjad; Tapper, William J; Gerty, Sue M; Hooning, Maartje J; Martens, John W M; Collée, J Margriet; Tilanus-Linthorst, Madeleine; Hall, Per; Li, Jingmei; Brand, Judith S; Humphreys, Keith; Cox, Angela; Reed, Malcolm W R; Luccarini, Craig; Baynes, Caroline; Dunning, Alison M; Hamann, Ute; Torres, Diana; Ulmer, Hans Ulrich; Rüdiger, Thomas; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Slager, Susan; Toland, Amanda E; Ambrosone, Christine B; Yannoukakos, Drakoulis; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Jones, Michael; González-Neira, Anna; Pita, Guillermo; Alonso, M Rosario; Álvarez, Nuria; Herrero, Daniel; Tessier, Daniel C; Vincent, Daniel; Bacot, Francois; Simard, Jacques; Dumont, Martine; Soucy, Penny; Eeles, Rosalind; Muir, Kenneth; Wiklund, Fredrik; Gronberg, Henrik; Schleutker, Johanna; Nordestgaard, Børge G; Weischer, Maren; Travis, Ruth C; Neal, David; Donovan, Jenny L; Hamdy, Freddie C; Khaw, Kay-Tee; Stanford, Janet L; Blot, William J; Thibodeau, Stephen; Schaid, Daniel J; Kelley, Joseph L; Maier, Christiane; Kibel, Adam S; Cybulski, Cezary; Cannon-Albright, Lisa; Butterbach, Katja; Park, Jong; Kaneva, Radka; Batra, Jyotsna; Teixeira, Manuel R; Kote-Jarai, Zsofia; Olama, Ali Amin Al; Benlloch, Sara; Renner, Stefan P; Hartmann, Arndt; Hein, Alexander; Ruebner, Matthias; Lambrechts, Diether; Van Nieuwenhuysen, Els; Vergote, Ignace; Lambretchs, Sandrina; Doherty, Jennifer A; Rossing, Mary Anne; Nickels, Stefan; Eilber, Ursula; Wang-Gohrke, Shan; Odunsi, Kunle; Sucheston-Campbell, Lara E; Friel, Grace; Lurie, Galina; Killeen, Jeffrey L; Wilkens, Lynne R; Goodman, Marc T; Runnebaum, Ingo; Hillemanns, Peter A; Pelttari, Liisa M; Butzow, Ralf; Modugno, Francesmary; Edwards, Robert P; Ness, Roberta B; Moysich, Kirsten B; du Bois, Andreas; Heitz, Florian; Harter, Philipp; Kommoss, Stefan; Karlan, Beth Y; Walsh, Christine; Lester, Jenny; Jensen, Allan; Kjaer, Susanne Krüger; Høgdall, Estrid; Peissel, Bernard; Bonanni, Bernardo; Bernard, Loris; Goode, Ellen L; Fridley, Brooke L; Vierkant, Robert A; Cunningham, Julie M; Larson, Melissa C; Fogarty, Zachary C; Kalli, Kimberly R; Liang, Dong; Lu, Karen H; Hildebrandt, Michelle A T; Wu, Xifeng; Levine, Douglas A; Dao, Fanny; Bisogna, Maria; Berchuck, Andrew; Iversen, Edwin S; Marks, Jeffrey R; Akushevich, Lucy; Cramer, Daniel W; Schildkraut, Joellen; Terry, Kathryn L; Poole, Elizabeth M; Stampfer, Meir; Tworoger, Shelley S; Bandera, Elisa V; Orlow, Irene; Olson, Sara H; Bjorge, Line; Salvesen, Helga B; van Altena, Anne M; Aben, Katja K H; Kiemeney, Lambertus A; Massuger, Leon F A G; Pejovic, Tanja; Bean, Yukie; Brooks-Wilson, Angela; Kelemen, Linda E; Cook, Linda S; Le, Nhu D; Górski, Bohdan; Gronwald, Jacek; Menkiszak, Janusz; Høgdall, Claus K; Lundvall, Lene; Nedergaard, Lotte; Engelholm, Svend Aage; Dicks, Ed; Tyrer, Jonathan; Campbell, Ian; McNeish, Iain; Paul, James; Siddiqui, Nadeem; Glasspool, Rosalind; Whittemore, Alice S; Rothstein, Joseph H; McGuire, Valerie; Sieh, Weiva; Cai, Hui; Shu, Xiao-Ou; Teten, Rachel T; Sutphen, Rebecca; McLaughlin, John R; Narod, Steven A; Phelan, Catherine M; Monteiro, Alvaro N; Fenstermacher, David; Lin, Hui-Yi; Permuth, Jennifer B; Sellers, Thomas A; Chen, Y Ann; Tsai, Ya-Yu; Chen, Zhihua; Gentry-Maharaj, Aleksandra; Gayther, Simon A; Ramus, Susan J; Menon, Usha; Wu, Anna H; Pearce, Celeste L; Van Den Berg, David; Pike, Malcolm C; Dansonka-Mieszkowska, Agnieszka; Plisiecka-Halasa, Joanna; Moes-Sosnowska, Joanna; Kupryjanczyk, Jolanta; Pharoah, Paul DP; Song, Honglin; Winship, Ingrid; Chenevix-Trench, Georgia; Giles, Graham G; Tavtigian, Sean V; Easton, Doug F; Milne, Roger L

    2016-01-01

    Background The rarity of mutations in PALB2, CHEK2 and ATM make it difficult to estimate precisely associated cancer risks. Population-based family studies have provided evidence that at least some of these mutations are associated with breast cancer risk as high as those associated with rare BRCA2 mutations. We aimed to estimate the relative risks associated with specific rare variants in PALB2, CHEK2 and ATM via a multicentre case-control study. Methods We genotyped 10 rare mutations using the custom iCOGS array: PALB2 c.1592delT, c.2816T>G and c.3113G>A, CHEK2 c.349A>G, c.538C>T, c.715G>A, c.1036C>T, c.1312G>T, and c.1343T>G and ATM c.7271T>G. We assessed associations with breast cancer risk (42 671 cases and 42 164 controls), as well as prostate (22 301 cases and 22 320 controls) and ovarian (14 542 cases and 23 491 controls) cancer risk, for each variant. Results For European women, strong evidence of association with breast cancer risk was observed for PALB2 c.1592delT OR 3.44 (95% CI 1.39 to 8.52, p=7.1×10−5), PALB2 c.3113G>A OR 4.21 (95% CI 1.84 to 9.60, p=6.9×10−8) and ATM c.7271T>G OR 11.0 (95% CI 1.42 to 85.7, p=0.0012). We also found evidence of association with breast cancer risk for three variants in CHEK2, c.349A>G OR 2.26 (95% CI 1.29 to 3.95), c.1036C>T OR 5.06 (95% CI 1.09 to 23.5) and c.538C>T OR 1.33 (95% CI 1.05 to 1.67) (p≤0.017). Evidence for prostate cancer risk was observed for CHEK2 c.1343T>G OR 3.03 (95% CI 1.53 to 6.03, p=0.0006) for African men and CHEK2 c.1312G>T OR 2.21 (95% CI 1.06 to 4.63, p=0.030) for European men. No evidence of association with ovarian cancer was found for any of these variants. Conclusions This report adds to accumulating evidence that at least some variants in these genes are associated with an increased risk of breast cancer that is clinically important. PMID:27595995

  9. Association between N-acetyltransferase 2 polymorphisms and pancreatic cancer risk: a meta-analysis.

    PubMed

    Liang, J X; Gao, W; Liang, Y; Zhou, X M

    2015-12-17

    N-acetyltransferase 2 (NAT2) is an essential phase II enzyme in the metabolism of aromatic and heterocyclic amines and of hydrazines. NAT2 activity can be divided into three phenotypes: rapid, intermediate, and slow. Studies identifying an association between NAT2 polymorphism and the risk of pancreatic cancer have shown conflicting results. In order to assess this relationship comprehensively, we performed a meta-analysis that involved 1607 patients with pancreatic cancer and 1682 controls from six studies, which were selected from a group of ten, identified by a search of PubMed and Embase databases up to July 2014. Relative risks (RRs) with 95% confidence intervals (CIs) were used to evaluate the relationships. In the overall analysis, no significant associations between NAT2 rapid acetylation genotypes and pancreatic cancer risk (RR = 0.93, 95%CI = 0.73-1.19) were found; however, the results showed significant heterogeneity (I2 = 55.0%). The results from subgroup analysis suggested that the rapid genotypes might decrease the risk of pancreatic cancer (RR = 0.56, 95%CI = 0.38-0.84) in Turkey, although the association was not significant in the United States population (RR = 0.97, 95%CI = 0.71-1.34) or in the multi-center studies (RR = 1.10, 95%CI = 0.90-1.34). Analysis of the slow acetylation genotypes demonstrated the converse outcomes. In conclusion, the results of our study suggested that the NAT2 slow acetylation genotypes might increase the susceptibility to pancreatic cancer in Europe but that these have no significant effects in the United States and multi-center populations.

  10. Predictive value of MRI-detected extramural vascular invasion in stage T3 rectal cancer patients before neoadjuvant chemoradiation.

    PubMed

    Sun, Yiqun; Li, Jianwen; Shen, Lijun; Wang, Xiaolin; Tong, Tong; Gu, Yajia

    2018-01-01

    We set out to explore the probability of MRI-detected extramural vascular invasion (mr-EMVI) before chemoradiation to predict responses to chemoradiation and survival in stage T3 rectal cancer patients. A total of 100 patients with T3 rectal cancer who underwent MRI examination and received neoadjuvant chemoradiation and surgery were enrolled. The correlation between mr-EMVI and other clinical factors were analyzed by chi-square. Logistic regression model was performed to select the potential factors influencing tumor responses to neoadjuvant chemoradiation. A Cox proportional hazards regression model was performed to explore potential predictors of survival. The positive mr-EMVI result was more likely to be present in patients with a higher T3 subgroup (T3a+b = 7.1% vs. T3c+d = 90.1%, P < 0.001) and more likely in patients with mesorectal fascia involvement than in those without MRF (65% vs. 38.8%, P = 0.034). Compared with mr-EMVI (+) patients, more mr-EMVI (-) patients showed a good response (staged ≤ ypT2N0) (odds ratio [OR], 3.020; 95% confidence interval [CI], 1.071-8.517; P = 0.037). In univariate analysis, mr-EMVI (+) (hazard ratio [HR], 5.374; 95% CI, 1.210-23.872; P = 0.027) and lower rectal cancers (HR, 3.326; 95% CI, 1.135-9.743; P = 0.028) were significantly associated with decreased disease-free survival. A positive mr-EMVI status (HR, 5.727; 95% CI, 1.286-25.594; P = 0.022) and lower rectal cancers (HR, 3.137; 95% CI, 1.127-8.729; P = 0.029) also served as prognostic factors related to decreased disease-free survival in multivariate analysis. The mr-EMVI status before chemoradiation is a significant prognostic factor and could be used for identifying T3 rectal cancer patients who might benefit from neoadjuvant chemoradiation.

  11. In vitro T lymphocyte adherence capabilities under the influence of lower induction values (0.1 - 0.01 mT) of 50 Hz external magnetic fields

    NASA Astrophysics Data System (ADS)

    Čoček, A.; Jandová, A.; Hahn, A.; Mártonová, J.; Ambruš, M.; Dohnalová, A.; Nedbalová, M.; Pokorný, J.

    2011-12-01

    Our research thus far has concerned the impact of external magnetic fields (50 Hz) and low (0.01-10 mT) induction on adherence capabilities of T lymphocytes obtained from the blood of patients with head and neck tumors. We know that the in vitro adherence capability of T lymphocytes towards surfaces in cancer patients is less than that of control. Previously, we have found that exposure to magnetic fields (50 Hz / 0.01-10 mT) increases the capability of T lymphocytes, in larynx/pharynx cancer patients, to adhere in vitro to surfaces, achieving almost physiological values, in not only pre-treatment patients but also those receiving treatment in the course of follow-up. The capability of T lymphocytes in controls (voluntary blood donors) to adhere to surfaces was also increased (50 Hz / 0.01-0.5 mT). The present study concentrates on the significance of the level of magnetic field induction in order to determine whether low induction values can restore T lymphocytes adherence capabilities. Testing a set of 20 patients showed a statistically significant difference (p < 0.05) in the in vitro adherence capacity of T lymphocytes between both 0.01 and 0.05, and 0.1 mT induction levels. In the control group (patients diagnosed with chronic sensorineural hearing loss) there was even a statistically significant difference between induction values of 0.05 and 0.01 mT. Therefore, we concluded that lower induction values resulted in a more biologically significant response.

  12. Differential association for N-acetyltransferase 2 genotype and phenotype with bladder cancer risk in Chinese population.

    PubMed

    Quan, Lei; Chattopadhyay, Koushik; Nelson, Heather H; Chan, Kenneth K; Xiang, Yong-Bing; Zhang, Wei; Wang, Renwei; Gao, Yu-Tang; Yuan, Jian-Min

    2016-06-28

    N-acetyltransferase 2 (NAT2) is involved in both carcinogen detoxification through hepatic N-acetylation and carcinogen activation through local O-acetylation. NAT2 slow acetylation status is significantly associated with increased bladder cancer risk among European populations, but its association in Asian populations is inconclusive. NAT2 acetylation status was determined by both single nucleotide polymorphisms (SNPs) and caffeine metabolic ratio (CMR), in a population-based study of 494 bladder cancer patients and 507 control subjects in Shanghai, China. The CMR, a functional measure of hepatic N-acetylation, was significantly reduced in a dose-dependent manner among both cases and controls possessing the SNP-inferred NAT2 slow acetylation status (all P-values<5.0×10-10). The CMR-determined slow N-acetylation status (CMR<0.34) was significantly associated with a 50% increased risk of bladder cancer (odds ratio = 1.50, 95% confidence interval = 1.10-2.06) whereas the SNP-inferred slow acetylation statuses were significantly associated with an approximately 50% decreased risk of bladder cancer. The genotype-disease association was strengthened after the adjustment for CMR and was primarily observed among never smokers. The apparent differential associations for phenotypic and genetic measures of acetylation statuses with bladder cancer risk may reflect dual functions of NAT2 in bladder carcinogenesis because the former only measures the capacity of carcinogen detoxification pathway while the latter represents both carcinogen activation and detoxification pathways. Future studies are warranted to ascertain the specific role of N- and O-acetylation in bladder carcinogenesis, particularly in populations exposed to different types of bladder carcinogens.

  13. Do Cartilage Repair Procedures Prevent Degenerative Meniscus Changes? Longitudinal T1ρ and Morphological Evaluation at 3.0T

    PubMed Central

    Jungmann, Pia M.; Li, Xiaojuan; Nardo, Lorenzo; Subburaj, Karupppasamy; Lin, Wilson; Ma, C. Benjamin; Majumdar, Sharmila; Link, Thomas M.

    2014-01-01

    Background Cartilage repair (CR) procedures are widely accepted for treatment of isolated cartilage defects at the knee joint. However, it is not well known whether these procedures prevent degenerative joint disease. Hypothesis/Purpose CR procedures prevent accelerated qualitative and quantitative progression of meniscus degeneration in individuals with focal cartilage defects. Study Design Cohort Study; Level of evidence 2b Methods A total of 94 subjects were studied. CR procedures were performed on 34 patients (n=16 osteochondral transplantation, n=18 microfracture); 34 controls were matched. An additional 13 patients received CR and anterior cruciate ligament (ACL) reconstruction (CR&ACL) and 13 patients received only ACL reconstruction. 3.0T MRI with T1ρ mapping and sagittal fat-saturated intermediate-weighted fast spin echo (FSE) sequences was performed to analyze menisci quantitatively and qualitatively (Whole-Organ Magnetic Resonance Imaging Score, WORMS). CR and CR&ACL patients were examined 4 months (n=34; n=13), 1 (n=21; n=8) and 2 (n=9; n=5) years post CR. Control subjects were scanned at baseline and after 1 and 2 years, ACL patients after 1 and 2 years. Results At baseline, global meniscus T1ρ values were higher in individuals with CR (14.2±0.6ms; P=0.004) and in individuals with CR&ACL (17.1±0.9ms; P<0.001) when compared to controls (12.8±0.6ms). After two years, there was a statistical difference between T1ρ at the overlying meniscus above cartilage defects (16.4±1.0ms) and T1ρ of the subgroup of control knees without cartilage defects (12.1±0.8ms; P<0.001) and a statistical trend to the CR group (13.3±1.0 ms; P=0.088). At baseline, 35% of subjects with CR showed morphological meniscus tears at the overlying meniscus; 10% of CR subjects showed an increase of WORMS meniscus score within the first year, none progressed in the second year. Control subjects with (without) cartilage defects showed meniscus tears in 30% (5%) at baseline; 38% (19

  14. Concordance of clinical diagnosis of T classification among physicians for locally advanced unresectable thoracic esophageal cancer.

    PubMed

    Yokota, Tomoya; Yasuda, Takushi; Kato, Hiroyuki; Nozaki, Isao; Sato, Hiroshi; Miyata, Yoshinori; Kuroki, Yoshifumi; Kato, Ken; Hamamoto, Yasuo; Tsubosa, Yasuhiro; Ogawa, Hirofumi; Ito, Yoshinori; Kitagawa, Yuko

    2018-02-01

    We conducted a multicenter phase II trial assessing chemoselection with docetaxel plus 5-fluorouracil and cisplatin induction chemotherapy and subsequent conversion surgery for locally advanced, unresectable esophageal cancer. The aim of this study was to validate the concordance of clinical T diagnosis among physicians in the cases of this trial. Computed tomography scans and esophagoscopic images of 48 patients taken at baseline were centrally reviewed by 6 senior physicians with experience in esophageal oncology. Individual reviewers voted for definitive T4, relative T4, relative T3, or definitive T3. Discordant diagnoses between reviewers were resolved by the majority opinion. The reviewers were blinded to patient clinical outcome data and to the vote of the other reviewers. Ninety percent of cases were diagnosed as clinical T4 by investigators, while 33.3-75.0% (median 70.8%) of cases were judged to be T4 by 6 reviewers. Discordant diagnosis between investigators and reviewers occurred in 33% (16/48) of all cases (Cohen's kappa coefficient 0.0519), including 12 cases where curative resection was considered possible (48%, n = 25) and 4 cases where curative resection was considered impossible (17%, n = 23). Critical discordance (one reviewer voted for definitive T3 but the other voted for definitive T4, and vice versa) between reviewers occurred in 0-12.5% of cases (median 2.1%). There were inter-observer variations in clinical diagnosis of the T category of locally advanced, unresectable esophageal cancer. Accurate clinical diagnosis of T classification is required for determining the optimum treatment for each patient.

  15. Motion corrected DWI with integrated T2-mapping for simultaneous estimation of ADC, T2-relaxation and perfusion in prostate cancer.

    PubMed

    Skorpil, M; Brynolfsson, P; Engström, M

    2017-06-01

    Multiparametric magnetic resonance imaging (MRI) and PI-RADS (Prostate Imaging - Reporting and Data System) has become the standard to determine a probability score for a lesion being a clinically significant prostate cancer. T2-weighted and diffusion-weighted imaging (DWI) are essential in PI-RADS, depending partly on visual assessment of signal intensity, while dynamic-contrast enhanced imaging is less important. To decrease inter-rater variability and further standardize image evaluation, complementary objective measures are in need. We here demonstrate a sequence enabling simultaneous quantification of apparent diffusion coefficient (ADC) and T2-relaxation, as well as calculation of the perfusion fraction f from low b-value intravoxel incoherent motion data. Expandable wait pulses were added to a FOCUS DW SE-EPI sequence, allowing the effective echo time to change at run time. To calculate both ADC and f, b-values 200s/mm 2 and 600s/mm 2 were chosen, and for T2-estimation 6 echo times between 64.9ms and 114.9ms were used. Three patients with prostate cancer were examined and all had significantly decreased ADC and T2-values, while f was significantly increased in 2 of 3 tumors. T2 maps obtained in phantom measurements and in a healthy volunteer were compared to T2 maps from a SE sequence with consecutive scans, showing good agreement. In addition, a motion correction procedure was implemented to reduce the effects of prostate motion, which improved T2-estimation. This sequence could potentially enable more objective tumor grading, and decrease the inter-rater variability in the PI-RADS classification. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. 2.0 to 2.4 micron spectroscopy of T Tauri stars

    NASA Astrophysics Data System (ADS)

    Hamann, F.; Simon, M.; Ridgway, S. T.

    1988-03-01

    Velocity-resolved 2.0-2.5-micron observations of the T Tau stars T, DF, DG, DK, HL, and RY Tau, SU Aur, and GW Ori are presented. For each of these stars except SU Aur, the Brackett gamma line was detected in emission with line widths inthe range of about 130-230 km/s. The Brackett gamma line profile of SU Aur is complex, having components of both emission and absorption. The first measurement of CO band-head emission in DG Tau is reported, and it is shown that published radio continuum fluxes of young stars far exceed what could be produced in an envelope ionized by only the stellar photospheric Lyman continuum. The excess of radio emission is found to be much greater in low-luminosity sources (e.g., the T Tau stars).

  17. Effects of Post Annealing on I-V-T Characteristics of (Ni/Au)/Al0.09Ga0.91N Schottky Barrier Diodes

    NASA Astrophysics Data System (ADS)

    Akkaya, Abdullah; Ayyıldız, Enise

    2016-04-01

    Post annealing is a simple, effective and suitable method for improving the diode parameters, especially when the used chemically stable substrates like Si, III-N and ternary alloys. In our work, we were applied this method to (Ni/Au)/Al0.09Ga0.91N Schottky Barrier Diodes (SBDs) and investigated by temperature-dependent current-voltage (I-V-T) characteristics at optimum conditions. Optimum annealing temperature was 600°C, which it’s determined with respect to have a highest barrier height value. The temperature-dependent electrical characteristics of the annealed at 600°C (Ni/Au)/Al0.09Ga0.91N SBDs were investigated in the wide temperature range of 95-315K. The diode parameters such as ideality factor (n) and Schottky barrier height (Vb0) were obtained to be strongly temperature dependent. The observed variation in Vb0 and n can be attributed to the spatial barrier inhomogeneities in Schottky barrier height by assuming a triple Gaussian distribution (TGD) of barrier heights (BHs) at 95-145K, 145-230K and 230-315K. The modified Richardson plots and T0 analysis was performed to provide an experimental Richardson constants and bias coefficients of the mean barrier height. Furthermore, the chemical composition of the contacts was examined by the XPS depth profile analysis.

  18. Esophageal Cancer: Associations With (pN+) Lymph Node Metastases.

    PubMed

    Rice, Thomas W; Ishwaran, Hemant; Hofstetter, Wayne L; Schipper, Paul H; Kesler, Kenneth A; Law, Simon; Lerut, E M R; Denlinger, Chadrick E; Salo, Jarmo A; Scott, Walter J; Watson, Thomas J; Allen, Mark S; Chen, Long-Qi; Rusch, Valerie W; Cerfolio, Robert J; Luketich, James D; Duranceau, Andre; Darling, Gail E; Pera, Manuel; Apperson-Hansen, Carolyn; Blackstone, Eugene H

    2017-01-01

    To identify the associations of lymph node metastases (pN+), number of positive nodes, and pN subclassification with cancer, treatment, patient, geographic, and institutional variables, and to recommend extent of lymphadenectomy needed to accurately detect pN+ for esophageal cancer. Limited data and traditional analytic techniques have precluded identifying intricate associations of pN+ with other cancer, treatment, and patient characteristics. Data on 5806 esophagectomy patients from the Worldwide Esophageal Cancer Collaboration were analyzed by Random Forest machine learning techniques. pN+, number of positive nodes, and pN subclassification were associated with increasing depth of cancer invasion (pT), increasing cancer length, decreasing cancer differentiation (G), and more regional lymph nodes resected. Lymphadenectomy necessary to accurately detect pN+ is 60 for shorter, well-differentiated cancers (<2.5 cm) and 20 for longer, poorly differentiated ones. In esophageal cancer, pN+, increasing number of positive nodes, and increasing pN classification are associated with deeper invading, longer, and poorly differentiated cancers. Consequently, if the goal of lymphadenectomy is to accurately define pN+ status of such cancers, few nodes need to be removed. Conversely, superficial, shorter, and well-differentiated cancers require a more extensive lymphadenectomy to accurately define pN+ status.

  19. T2- and diffusion-weighted magnetic resonance imaging at 3T for the detection of prostate cancer with and without endorectal coil: An intraindividual comparison of image quality and diagnostic performance.

    PubMed

    Baur, Alexander D J; Daqqaq, Tareef; Wagner, Moritz; Maxeiner, Andreas; Huppertz, Alexander; Renz, Diane; Hamm, Bernd; Fischer, Thomas; Durmus, Tahir

    2016-06-01

    To intraindividually compare image quality and diagnostic performance of multiparametric MRI (mpMRI) at 3T for the detection of prostate cancer (PCa) using a pelvic phased-array coil (PAC) and a combined endorectal and pelvic phased-array coil (ERC-PAC). Forty-five patients were prospectively included and received mpMRI of the prostate using a PAC and an ERC-PAC during one imaging session. Two radiologists evaluated image quality and the most suspicious lesion according to the PI-RADS scoring system. Results of MRI-TRUS-fusion biopsy of the prostate served as reference standard. Patient comfort and acceptance were assessed using a standardized questionnaire. Overall image quality for T2WI was rated significantly better with an ERC-PAC compared to a PAC (p=0.0038). The weighted kappa for PI-RADS scores for T2WI and DWI with a PAC and an ERC-PAC was 0.70 and 0.73, respectively. For a PI-RADS sum score including T2WI and DWI the area under the curve with a PAC and an ERC-PAC were 0.95-0.99 and 0.93-0.97, respectively (p=0.1395). For T2WI and DWI performed at 3T index PCa lesion identification and evaluation did not differ significantly with both coil setups. Patients preferred MRI without an ERC. Therefore, the use of an ERC may be omitted in a prostate cancer detection setting. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers.

    PubMed

    Blein, Sophie; Bardel, Claire; Danjean, Vincent; McGuffog, Lesley; Healey, Sue; Barrowdale, Daniel; Lee, Andrew; Dennis, Joe; Kuchenbaecker, Karoline B; Soucy, Penny; Terry, Mary Beth; Chung, Wendy K; Goldgar, David E; Buys, Saundra S; Janavicius, Ramunas; Tihomirova, Laima; Tung, Nadine; Dorfling, Cecilia M; van Rensburg, Elizabeth J; Neuhausen, Susan L; Ding, Yuan Chun; Gerdes, Anne-Marie; Ejlertsen, Bent; Nielsen, Finn C; Hansen, Thomas Vo; Osorio, Ana; Benitez, Javier; Conejero, Raquel Andrés; Segota, Ena; Weitzel, Jeffrey N; Thelander, Margo; Peterlongo, Paolo; Radice, Paolo; Pensotti, Valeria; Dolcetti, Riccardo; Bonanni, Bernardo; Peissel, Bernard; Zaffaroni, Daniela; Scuvera, Giulietta; Manoukian, Siranoush; Varesco, Liliana; Capone, Gabriele L; Papi, Laura; Ottini, Laura; Yannoukakos, Drakoulis; Konstantopoulou, Irene; Garber, Judy; Hamann, Ute; Donaldson, Alan; Brady, Angela; Brewer, Carole; Foo, Claire; Evans, D Gareth; Frost, Debra; Eccles, Diana; Douglas, Fiona; Cook, Jackie; Adlard, Julian; Barwell, Julian; Walker, Lisa; Izatt, Louise; Side, Lucy E; Kennedy, M John; Tischkowitz, Marc; Rogers, Mark T; Porteous, Mary E; Morrison, Patrick J; Platte, Radka; Eeles, Ros; Davidson, Rosemarie; Hodgson, Shirley; Cole, Trevor; Godwin, Andrew K; Isaacs, Claudine; Claes, Kathleen; De Leeneer, Kim; Meindl, Alfons; Gehrig, Andrea; Wappenschmidt, Barbara; Sutter, Christian; Engel, Christoph; Niederacher, Dieter; Steinemann, Doris; Plendl, Hansjoerg; Kast, Karin; Rhiem, Kerstin; Ditsch, Nina; Arnold, Norbert; Varon-Mateeva, Raymonda; Schmutzler, Rita K; Preisler-Adams, Sabine; Markov, Nadja Bogdanova; Wang-Gohrke, Shan; de Pauw, Antoine; Lefol, Cédrick; Lasset, Christine; Leroux, Dominique; Rouleau, Etienne; Damiola, Francesca; Dreyfus, Hélène; Barjhoux, Laure; Golmard, Lisa; Uhrhammer, Nancy; Bonadona, Valérie; Sornin, Valérie; Bignon, Yves-Jean; Carter, Jonathan; Van Le, Linda; Piedmonte, Marion; DiSilvestro, Paul A; de la Hoya, Miguel; Caldes, Trinidad; Nevanlinna, Heli; Aittomäki, Kristiina; Jager, Agnes; van den Ouweland, Ans Mw; Kets, Carolien M; Aalfs, Cora M; van Leeuwen, Flora E; Hogervorst, Frans Bl; Meijers-Heijboer, Hanne Ej; Oosterwijk, Jan C; van Roozendaal, Kees Ep; Rookus, Matti A; Devilee, Peter; van der Luijt, Rob B; Olah, Edith; Diez, Orland; Teulé, Alex; Lazaro, Conxi; Blanco, Ignacio; Del Valle, Jesús; Jakubowska, Anna; Sukiennicki, Grzegorz; Gronwald, Jacek; Lubinski, Jan; Durda, Katarzyna; Jaworska-Bieniek, Katarzyna; Agnarsson, Bjarni A; Maugard, Christine; Amadori, Alberto; Montagna, Marco; Teixeira, Manuel R; Spurdle, Amanda B; Foulkes, William; Olswold, Curtis; Lindor, Noralane M; Pankratz, Vernon S; Szabo, Csilla I; Lincoln, Anne; Jacobs, Lauren; Corines, Marina; Robson, Mark; Vijai, Joseph; Berger, Andreas; Fink-Retter, Anneliese; Singer, Christian F; Rappaport, Christine; Kaulich, Daphne Geschwantler; Pfeiler, Georg; Tea, Muy-Kheng; Greene, Mark H; Mai, Phuong L; Rennert, Gad; Imyanitov, Evgeny N; Mulligan, Anna Marie; Glendon, Gord; Andrulis, Irene L; Tchatchou, Sandrine; Toland, Amanda Ewart; Pedersen, Inge Sokilde; Thomassen, Mads; Kruse, Torben A; Jensen, Uffe Birk; Caligo, Maria A; Friedman, Eitan; Zidan, Jamal; Laitman, Yael; Lindblom, Annika; Melin, Beatrice; Arver, Brita; Loman, Niklas; Rosenquist, Richard; Olopade, Olufunmilayo I; Nussbaum, Robert L; Ramus, Susan J; Nathanson, Katherine L; Domchek, Susan M; Rebbeck, Timothy R; Arun, Banu K; Mitchell, Gillian; Karlan, Beth Y; Lester, Jenny; Orsulic, Sandra; Stoppa-Lyonnet, Dominique; Thomas, Gilles; Simard, Jacques; Couch, Fergus J; Offit, Kenneth; Easton, Douglas F; Chenevix-Trench, Georgia; Antoniou, Antonis C; Mazoyer, Sylvie; Phelan, Catherine M; Sinilnikova, Olga M; Cox, David G

    2015-04-25

    Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.

  1. [Factors influencing survival and recurrence and potential significance of postoperative radiotherapy and adjuvant chemotherapy for stage ⅢA-N2 non-small cell lung cancer].

    PubMed

    Han, W; Song, Y Z; He, M; Li, J; Zhang, R; Qiao, X Y

    2016-11-23

    Objective: To investigate the survival, recurrence patterns and risk factors in patients with stage ⅢA-N2 NSCLC treated with curative surgery and adjuvant chemotherapy and to explore the significance of postoperative radiation therapy. Methods: The clinical data of 290 patients with pathologically diagnosed stage ⅢA-N2 NSCLC after curative resection and adjuvant chemotherapy from January 2010 to December 2014 at our department were retrospectively analyzed. The survival and recurrence patterns were observed, and the factors affecting locoregional recurrence were analyzed. Results: The median survival time was 31.5 months. The 1-, 3-and 5-year survival rates were 88.3%, 46.0% and 33.2%, respectively. The median locoregional control time was 38.5 months. The 1-, 3-and 5-year locoregional control rates were 78.6%, 55.2% and 41.0%, respectively. The median distant metastasis-free survival was 26.8 months. The 1-, 3-and 5-year distant metastasis-free survival rates were 76.4%, 45.5% and 39.5%, respectively. The median progression-free survival was 19.1 months. The 1-, 3-and 5-year progression-free survival rates were 64.1%, 32.5% and 23.8%, respectively. Univariate analysis showed that clinical N status, histological type, pathological T stage, operation mode, the number of positive N2 lymph nodes and the number of positive N2 lymph node stations had a significant influence on overall survival; clinical N status, histological type, the number of positive N2 lymph nodes and the number of positive N2 lymph node stations had a significant influence on locoregional control. Multivariate analysis demonstrated that the number of N2 positive lymph nodes ( P = 0.017) was an independent factor for overall survival of stage ⅢA-N2 patients; the number of N2 positive lymph nodes ( P =0.009) and histological type ( P =0.005) were independent factors for locoregional recurrence. For left-sided lung cancer, the lymph node station failure sites were mostly in 2R, 4R, 5, 6 and 7

  2. PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS.

    PubMed

    Southey, Melissa C; Goldgar, David E; Winqvist, Robert; Pylkäs, Katri; Couch, Fergus; Tischkowitz, Marc; Foulkes, William D; Dennis, Joe; Michailidou, Kyriaki; van Rensburg, Elizabeth J; Heikkinen, Tuomas; Nevanlinna, Heli; Hopper, John L; Dörk, Thilo; Claes, Kathleen Bm; Reis-Filho, Jorge; Teo, Zhi Ling; Radice, Paolo; Catucci, Irene; Peterlongo, Paolo; Tsimiklis, Helen; Odefrey, Fabrice A; Dowty, James G; Schmidt, Marjanka K; Broeks, Annegien; Hogervorst, Frans B; Verhoef, Senno; Carpenter, Jane; Clarke, Christine; Scott, Rodney J; Fasching, Peter A; Haeberle, Lothar; Ekici, Arif B; Beckmann, Matthias W; Peto, Julian; Dos-Santos-Silva, Isabel; Fletcher, Olivia; Johnson, Nichola; Bolla, Manjeet K; Sawyer, Elinor J; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Marme, Federik; Burwinkel, Barbara; Yang, Rongxi; Guénel, Pascal; Truong, Thérèse; Menegaux, Florence; Sanchez, Marie; Bojesen, Stig; Nielsen, Sune F; Flyger, Henrik; Benitez, Javier; Zamora, M Pilar; Perez, Jose Ignacio Arias; Menéndez, Primitiva; Anton-Culver, Hoda; Neuhausen, Susan; Ziogas, Argyrios; Clarke, Christina A; Brenner, Hermann; Arndt, Volker; Stegmaier, Christa; Brauch, Hiltrud; Brüning, Thomas; Ko, Yon-Dschun; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Bogdanova, Natalia V; Antonenkova, Natalia N; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Spurdle, Amanda B; Investigators, kConFab; Wauters, Els; Smeets, Dominiek; Beuselinck, Benoit; Floris, Giuseppe; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Olson, Janet E; Vachon, Celine; Pankratz, Vernon S; McLean, Catriona; Haiman, Christopher A; Henderson, Brian E; Schumacher, Fredrick; Le Marchand, Loic; Kristensen, Vessela; Alnæs, Grethe Grenaker; Zheng, Wei; Hunter, David J; Lindstrom, Sara; Hankinson, Susan E; Kraft, Peter; Andrulis, Irene; Knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Jukkola-Vuorinen, Arja; Grip, Mervi; Kauppila, Saila; Devilee, Peter; Tollenaar, Robert A E M; Seynaeve, Caroline; Hollestelle, Antoinette; Garcia-Closas, Montserrat; Figueroa, Jonine; Chanock, Stephen J; Lissowska, Jolanta; Czene, Kamila; Darabi, Hatef; Eriksson, Mikael; Eccles, Diana M; Rafiq, Sajjad; Tapper, William J; Gerty, Sue M; Hooning, Maartje J; Martens, John W M; Collée, J Margriet; Tilanus-Linthorst, Madeleine; Hall, Per; Li, Jingmei; Brand, Judith S; Humphreys, Keith; Cox, Angela; Reed, Malcolm W R; Luccarini, Craig; Baynes, Caroline; Dunning, Alison M; Hamann, Ute; Torres, Diana; Ulmer, Hans Ulrich; Rüdiger, Thomas; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Slager, Susan; Toland, Amanda E; Ambrosone, Christine B; Yannoukakos, Drakoulis; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Jones, Michael; González-Neira, Anna; Pita, Guillermo; Alonso, M Rosario; Álvarez, Nuria; Herrero, Daniel; Tessier, Daniel C; Vincent, Daniel; Bacot, Francois; Simard, Jacques; Dumont, Martine; Soucy, Penny; Eeles, Rosalind; Muir, Kenneth; Wiklund, Fredrik; Gronberg, Henrik; Schleutker, Johanna; Nordestgaard, Børge G; Weischer, Maren; Travis, Ruth C; Neal, David; Donovan, Jenny L; Hamdy, Freddie C; Khaw, Kay-Tee; Stanford, Janet L; Blot, William J; Thibodeau, Stephen; Schaid, Daniel J; Kelley, Joseph L; Maier, Christiane; Kibel, Adam S; Cybulski, Cezary; Cannon-Albright, Lisa; Butterbach, Katja; Park, Jong; Kaneva, Radka; Batra, Jyotsna; Teixeira, Manuel R; Kote-Jarai, Zsofia; Olama, Ali Amin Al; Benlloch, Sara; Renner, Stefan P; Hartmann, Arndt; Hein, Alexander; Ruebner, Matthias; Lambrechts, Diether; Van Nieuwenhuysen, Els; Vergote, Ignace; Lambretchs, Sandrina; Doherty, Jennifer A; Rossing, Mary Anne; Nickels, Stefan; Eilber, Ursula; Wang-Gohrke, Shan; Odunsi, Kunle; Sucheston-Campbell, Lara E; Friel, Grace; Lurie, Galina; Killeen, Jeffrey L; Wilkens, Lynne R; Goodman, Marc T; Runnebaum, Ingo; Hillemanns, Peter A; Pelttari, Liisa M; Butzow, Ralf; Modugno, Francesmary; Edwards, Robert P; Ness, Roberta B; Moysich, Kirsten B; du Bois, Andreas; Heitz, Florian; Harter, Philipp; Kommoss, Stefan; Karlan, Beth Y; Walsh, Christine; Lester, Jenny; Jensen, Allan; Kjaer, Susanne Krüger; Høgdall, Estrid; Peissel, Bernard; Bonanni, Bernardo; Bernard, Loris; Goode, Ellen L; Fridley, Brooke L; Vierkant, Robert A; Cunningham, Julie M; Larson, Melissa C; Fogarty, Zachary C; Kalli, Kimberly R; Liang, Dong; Lu, Karen H; Hildebrandt, Michelle A T; Wu, Xifeng; Levine, Douglas A; Dao, Fanny; Bisogna, Maria; Berchuck, Andrew; Iversen, Edwin S; Marks, Jeffrey R; Akushevich, Lucy; Cramer, Daniel W; Schildkraut, Joellen; Terry, Kathryn L; Poole, Elizabeth M; Stampfer, Meir; Tworoger, Shelley S; Bandera, Elisa V; Orlow, Irene; Olson, Sara H; Bjorge, Line; Salvesen, Helga B; van Altena, Anne M; Aben, Katja K H; Kiemeney, Lambertus A; Massuger, Leon F A G; Pejovic, Tanja; Bean, Yukie; Brooks-Wilson, Angela; Kelemen, Linda E; Cook, Linda S; Le, Nhu D; Górski, Bohdan; Gronwald, Jacek; Menkiszak, Janusz; Høgdall, Claus K; Lundvall, Lene; Nedergaard, Lotte; Engelholm, Svend Aage; Dicks, Ed; Tyrer, Jonathan; Campbell, Ian; McNeish, Iain; Paul, James; Siddiqui, Nadeem; Glasspool, Rosalind; Whittemore, Alice S; Rothstein, Joseph H; McGuire, Valerie; Sieh, Weiva; Cai, Hui; Shu, Xiao-Ou; Teten, Rachel T; Sutphen, Rebecca; McLaughlin, John R; Narod, Steven A; Phelan, Catherine M; Monteiro, Alvaro N; Fenstermacher, David; Lin, Hui-Yi; Permuth, Jennifer B; Sellers, Thomas A; Chen, Y Ann; Tsai, Ya-Yu; Chen, Zhihua; Gentry-Maharaj, Aleksandra; Gayther, Simon A; Ramus, Susan J; Menon, Usha; Wu, Anna H; Pearce, Celeste L; Van Den Berg, David; Pike, Malcolm C; Dansonka-Mieszkowska, Agnieszka; Plisiecka-Halasa, Joanna; Moes-Sosnowska, Joanna; Kupryjanczyk, Jolanta; Pharoah, Paul Dp; Song, Honglin; Winship, Ingrid; Chenevix-Trench, Georgia; Giles, Graham G; Tavtigian, Sean V; Easton, Doug F; Milne, Roger L

    2016-12-01

    The rarity of mutations in PALB2, CHEK2 and ATM make it difficult to estimate precisely associated cancer risks. Population-based family studies have provided evidence that at least some of these mutations are associated with breast cancer risk as high as those associated with rare BRCA2 mutations. We aimed to estimate the relative risks associated with specific rare variants in PALB2, CHEK2 and ATM via a multicentre case-control study. We genotyped 10 rare mutations using the custom iCOGS array: PALB2 c.1592delT, c.2816T>G and c.3113G>A, CHEK2 c.349A>G, c.538C>T, c.715G>A, c.1036C>T, c.1312G>T, and c.1343T>G and ATM c.7271T>G. We assessed associations with breast cancer risk (42 671 cases and 42 164 controls), as well as prostate (22 301 cases and 22 320 controls) and ovarian (14 542 cases and 23 491 controls) cancer risk, for each variant. For European women, strong evidence of association with breast cancer risk was observed for PALB2 c.1592delT OR 3.44 (95% CI 1.39 to 8.52, p=7.1×10 -5 ), PALB2 c.3113G>A OR 4.21 (95% CI 1.84 to 9.60, p=6.9×10 -8 ) and ATM c.7271T>G OR 11.0 (95% CI 1.42 to 85.7, p=0.0012). We also found evidence of association with breast cancer risk for three variants in CHEK2, c.349A>G OR 2.26 (95% CI 1.29 to 3.95), c.1036C>T OR 5.06 (95% CI 1.09 to 23.5) and c.538C>T OR 1.33 (95% CI 1.05 to 1.67) (p≤0.017). Evidence for prostate cancer risk was observed for CHEK2 c.1343T>G OR 3.03 (95% CI 1.53 to 6.03, p=0.0006) for African men and CHEK2 c.1312G>T OR 2.21 (95% CI 1.06 to 4.63, p=0.030) for European men. No evidence of association with ovarian cancer was found for any of these variants. This report adds to accumulating evidence that at least some variants in these genes are associated with an increased risk of breast cancer that is clinically important. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  3. Association of maximum standardized uptake value with occult mediastinal lymph node metastases in cN0 non-small cell lung cancer.

    PubMed

    Lin, Jun-Tao; Yang, Xue-Ning; Zhong, Wen-Zhao; Liao, Ri-Qiang; Dong, Song; Nie, Qiang; Weng, Si-Xian; Fang, Xiao-Jing; Zheng, Jun-Yi; Wu, Yi-Long

    2016-11-01

    The management of non-small cell lung cancer (NSCLC) relies on the tumour-node-metastasis (TNM) stage, and the treatment regimen differs based on the N status. Positron emission tomography-computed tomography (PET-CT) has emerged as a powerful imaging tool for the detection of various cancers with a relatively low false-negative rate. We explored predictors to identify false-negative N2 disease in PET-CT. A total of 284 consecutive cN0 patients with peripheral NSCLC who underwent PET-CT scans followed by curative intent resections were enrolled as a training set to identify predictors of occult N2 metastases by multivariable analysis. The accuracy and cut-off values for the predictors were calculated using a receiver operating characteristic curve. Clinical and pathological data were analysed retrospectively. An additional 151 patients were collected as a test set to validate the results, including the occult N2 rate and accuracy. In total, 8.5% (24/284) PET-CT-diagnosed N0 NSCLC cases had pathologically diagnosed N2 metastases. The SUV max of the primary tumour was a unique independent risk factor for occult N2 NSCLC [P = 0.003, 95% confidence interval = 0.81-0.96, odds ratio (OR) = 0.88]. Occult N2 metastases occurred more frequently in the subcarinal (16/24) and right lower paratracheal lymph nodes (12/24). Accordingly, we divided the patients into two groups by SUV max : the occult N2 rates in the SUV max of <2.6 and SUV max of ≥2.6 groups were 1.0% (1/100) and 12.5% (23/184), respectively (P = 0.001). In the test set, the occult N2 incidence rate was 9.3% (14/151), with the highest rates occurring in the subcarinal (9/14) and right lower paratracheal lymph nodes (6/14). In the two groups defined by SUV max , the occult N2 rates were 4% (2/50) and 11.9% (12/101), respectively. The SUV max of the primary tumour was an independent risk factor for occult N2 metastases in NSCLC patients diagnosed as clinical N0 by PET-CT. SUV max of ≥2.6 of the primary tumour

  4. Correlation between preoperative tomographic staging and definitive histopathologic results in gastric cancer at the Hospital Central Militar.

    PubMed

    López-Ramírez, M A; Lever-Rosas, C D; Motta-Ramírez, G A; Rebollo-Hurtado, V; Guzmán-Bárcenas, J; Fonseca-Morales, J V; Carreño-Lomeli, M A

    In relation to the number of new cases diagnosed, gastric cancer is the fourth most common cancer worldwide, and the second cause of cancer death. The development of multidetector tomography has improved the preoperative staging of gastric cancer. To correlate preoperative tomographic studies with the definitive pathologic results according to the TNM staging system. A retrospective, cross-sectional study within the time frame of January 2009 to December 2013 was conducted that included the case records of 67 patients. They all had upper endoscopy and preoperative multidetector tomography examinations, underwent surgical resection, and had the corresponding histopathology study. Statistical analysis was carried out with the SPSS version 15.0 software and the sensitivity and specificity calculations were made using the Excel 2011 program for Mac. The majority of the patients included in the case series had clinical stage iii and iv disease. When compared with the histopathologic result, the overall accuracy of multidetector CT was 83% (T0 96%, T1 94%, T2 93%, T3 67%, and T4 67%) for tumor size (T) and was 70% (N0 72%, N1 73%, N2 70%, and N3 66%) for lymph node involvement (N). Overall sensitivity was 48% (T0 100%, T1 0%, T2 33%, T3 44%, and T4 65%) for T and was 41% (N0 58%, N1 56%, N2 15%, and N3 35%) for N. A strong association between the multidetector CT results and the pathology results was demonstrated through the Spearman's correlation, especially in T4 and N3. Multidetector computed tomography showed greater congruency in detecting stages T4, N0, and N3 in gastric cancer, when compared with the definitive histopathologic results. Copyright © 2017 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

  5. Worldwide Esophageal Cancer Collaboration: neoadjuvant pathologic staging data.

    PubMed

    Rice, T W; Lerut, T E M R; Orringer, M B; Chen, L-Q; Hofstetter, W L; Smithers, B M; Rusch, V W; van Lanschot, J; Chen, K N; Davies, A R; D'Journo, X B; Kesler, K A; Luketich, J D; Ferguson, M K; Räsänen, J V; van Hillegersberg, R; Fang, W; Durand, L; Allum, W H; Cecconello, I; Cerfolio, R J; Pera, M; Griffin, S M; Burger, R; Liu, J-F; Allen, M S; Law, S; Watson, T J; Darling, G E; Scott, W J; Duranceau, A; Denlinger, C E; Schipper, P H; Ishwaran, H; Apperson-Hansen, C; DiPaola, L M; Semple, M E; Blackstone, E H

    2016-10-01

    To address uncertainty of whether pathologic stage groupings after neoadjuvant therapy (ypTNM) for esophageal cancer share prognostic implications with pathologic groupings after esophagectomy alone (pTNM), we report data-simple descriptions of patient characteristics, cancer categories, and non-risk-adjusted survival-for pathologically staged cancers after neoadjuvant therapy from the Worldwide Esophageal Cancer Collaboration (WECC). Thirty-three institutions from six continents submitted data using variables with standard definitions: demographics, comorbidities, clinical cancer categories, and all-cause mortality from first management decision. Of 7,773 pathologically staged neoadjuvant patients, 2,045 had squamous cell carcinoma, 5,686 adenocarcinoma, 31 adenosquamous carcinoma, and 11 undifferentiated carcinoma. Patients were older (61 years) men (83%) with normal (40%) or overweight (35%) body mass index, 0-1 Eastern Cooperative Oncology Group performance status (96%), and a history of smoking (69%). Cancers were ypT0 (20%), ypT1 (13%), ypT2 (18%), ypT3 (44%), ypN0 (55%), ypM0 (94%), and G2-G3 (72%); most involved the distal esophagus (80%). Non-risk-adjusted survival for yp categories was unequally depressed, more for earlier categories than later, compared with equivalent categories from prior WECC data for esophagectomy-alone patients. Thus, survival of patients with ypT0-2N0M0 cancers was intermediate and similar regardless of ypT; survival for ypN+ cancers was poor. Because prognoses for ypTNM and pTNM categories are dissimilar, prognostication should be based on separate ypTNM categories and groupings. These data will be the basis for the 8th edition cancer staging manuals following risk adjustment for patient, cancer, and treatment characteristics and should direct 9th edition data collection. © 2016 International Society for Diseases of the Esophagus.

  6. Worldwide Esophageal Cancer Collaboration: neoadjuvant pathologic staging data

    PubMed Central

    Rice, T. W.; Lerut, T. E. M. R.; Orringer, M. B.; Chen, L.-Q.; Hofstetter, W. L.; Smithers, B. M.; Rusch, V. W.; van Lanschot, J.; Chen, K. N.; Davies, A. R.; D’Journo, X. B.; Kesler, K. A.; Luketich, J. D.; Ferguson, M. K.; Rasanen, J. V.; van Hillegersberg, R.; Fang, W.; Durand, L.; Allum, W. H.; Cecconello, I.; Cerfolio, R. J.; Pera, M.; Griffin, S. M.; Burger, R.; Liu, J.-F.; Allen, M. S.; Law, S.; Watson, T. J.; Darling, G. E.; Scott, W. J.; Duranceau, A.; Denlinger, C. E.; Schipper, P. H.; Ishwaran, H.; Apperson-Hansen, C.; DiPaola, L. M.; Semple, M. E.; Blackstone, E. H.

    2017-01-01

    SUMMARY To address uncertainty of whether pathologic stage groupings after neoadjuvant therapy (ypTNM) for esophageal cancer share prognostic implications with pathologic groupings after esophagectomy alone (pTNM), we report data—simple descriptions of patient characteristics, cancer categories, and non–risk-adjusted survival—for pathologically staged cancers after neoadjuvant therapy from the Worldwide Esophageal Cancer Collaboration (WECC). Thirty-three institutions from six continents submitted data using variables with standard definitions: demographics, comorbidities, clinical cancer categories, and all-cause mortality from first management decision. Of 7,773 pathologically staged neoadjuvant patients, 2,045 had squamous cell carcinoma, 5,686 adenocarcinoma, 31 adenosquamous carcinoma, and 11 undifferentiated carcinoma. Patients were older (61 years) men (83%) with normal (40%) or overweight (35%) body mass index, 0–1 Eastern Cooperative Oncology Group performance status (96%), and a history of smoking (69%). Cancers were ypT0 (20%), ypT1 (13%), ypT2 (18%), ypT3 (44%), ypN0 (55%), ypM0 (94%), and G2-G3 (72%); most involved the distal esophagus (80%). Non–risk-adjusted survival for yp categories was unequally depressed, more for earlier categories than later, compared with equivalent categories from prior WECC data for esophagectomy-alone patients. Thus, survival of patients with ypT0-2N0M0 cancers was intermediate and similar regardless of ypT; survival for ypN+ cancers was poor. Because prognoses for ypTNM and pTNM categories are dissimilar, prognostication should be based on separate ypTNM categories and groupings. These data will be the basis for the 8th edition cancer staging manuals following risk adjustment for patient, cancer, and treatment characteristics and should direct 9th edition data collection. PMID:27731548

  7. Rectal cancer confined to the bowel wall: the role of 3 Tesla phased-array MR imaging in T categorization.

    PubMed

    Çolakoğlu Er, Hale; Peker, Elif; Erden, Ayşe; Erden, İlhan; Geçim, Ethem; Savaş, Berna

    2018-02-01

    To determine the diagnostic value of 3 Tesla MR imaging in detection of mucosal (Tis), submucosal (T 1 ) and muscularis propria (T 2 ) invasion in patients with early rectal cancer. A total of 50 consecutive patients who underwent 3 Tesla MR imaging and curative-intent intervention for MRI-staged Tis/T 1 /T 2 rectal cancer from March 2012 to December 2016 were included. The radiological T category of each rectal tumour was compared retrospectively with histopathological results assessed according to the tumor, node, metastasis (TNM) classification. The sensitivities, specificities, and overall accuracy rates of 3 Tesla MR imaging for Tis, T 1 , and T 2 cases were calculated using MedCalc statistical software v. 16. The sensitivity, specificity, PPV, NPV of 3 Tesla MR imaging in T categorization for T 2 were: 93.7% [95% CI (0.79-0.99)], 77.7% [95% CI (0.52-0.93)], 88.2% [95% CI (0.75-0.94)] and 87.5% [95% CI (0.64-0.96)]; for T 1 were 92% [95% CI (0.63-0.99)], 91.8% [95% CI (0.78-0.98)], 80% [95% CI (0.57-0.92)] and 97.1% [95% CI (0.83-0.99)]; for Tis were: 20% [95% CI (0.51-0.71)], 100% [95% CI (0.92-1)], 100%, 91.8% [95% CI (0.87-0.94)], respectively. MR categorization accuracy rates for T 2 , T 1 and Tis were calculated as 88, 92 and 92%, respectively. 3 Tesla MR imaging seems to be useful for accurate categorization of T-stage in early rectal cancer, especially for T 1 cancers. The method is not a reliable tool to detect Tis cases. The potential for overstaging and understaging of the technique should be realized and taken into consideration when tailoring the treatment protocol for each patient. Advances in knowledge: High-resolution MR with phased-array coil is being increasingly used in the pre-operative assessment of rectal cancer. 3 Tesla high-resolution MR imaging allows improved definition of bowel wall and tumour infiltration.

  8. 7-(O)-Carboxymethyl daidzein conjugated to N-t-Boc-hexylenediamine: A Novel Compound Capable of Inducing Cell Death in Epithelial Ovarian Cancer Stem Cells

    PubMed Central

    Green, Jamie M.; Alvero, Ayesha B.; Kohen, Fortune; Mor, Gil

    2009-01-01

    One of the major difficulties in the treatment of epithelial ovarian cancer (EOC) is the high rate of recurrent disease. This is thought to be due to the survival of a population of chemo-resistant cells within the tumor, the ovarian cancer stem cells (OCSCs), that are able to regenerate the tumor following chemotherapy. Therefore, the identification of a compund that can target the OCSCs is one of the main steps in improving overall survival of ovarian cancer patients. The objective of this study was to determine the effect of N-t-boc-Daidzein, a novel daidzain derivative, on OCSCs. The efficacy of this compound was evaluated in OCSC and mature ovarian cancer cell (mOCC) lines isolated from malignant ovarian cancer asicites. Cells were treated with increasing concentrations of N-t-boc-Daidzein (0.003–10 μM) and cell growth was monitored by “real time in vitro micro-imaging” using the IncuCyte system. Cell viability was measured using the CellTiter 96 Assay. Apoptosis was determined by Caspase-Glo 3/7, 8, and 9 assays. The components of the apoptotic cascade were characterized by Western blot analysis. N-t-boc-Daidzein was able to significantly inhibit cell growth and decrease cell viability of OCSC as well as mOCC cells in a dose and time dependent maner. This effect was due to the induction of apoptosis, which is characterized by caspase activation, XIAP and AKT degradation, and mitochondrial depolarization. This study describes a novel compound that can target the OCSCs. These findings may provide vital aide in improving overall survival in patients with EOC. PMID:19738422

  9. 7-(O)-Carboxymethyl daidzein conjugated to N-t-Boc-hexylenediamine: a novel compound capable of inducing cell death in epithelial ovarian cancer stem cells.

    PubMed

    Green, Jamie M; Alvero, Ayesha B; Kohen, Fortune; Mor, Gil

    2009-09-01

    One of the major difficulties in the treatment of epithelial ovarian cancer (EOC) is the high rate of recurrent disease. This is thought to be due to the survival of a population of chemo-resistant cells within the tumor, the ovarian cancer stem cells (OCSCs), that are able to regenerate the tumor following chemotherapy. Therefore, the identification of a compund that can target the OCSCs is one of the main steps in improving overall survival of ovarian cancer patients. The objective of this study was to determine the effect of N-t-boc-Daidzein, a novel daidzain derivative, on OCSCs. The efficacy of this compound was evaluated in OCSC and mature ovarian cancer cell (mOCC) lines isolated from malignant ovarian cancer asicites. Cells were treated with increasing concentrations of N-t-boc-Daidzein (0.003-10 microM) and cell growth was monitored by "real time in vitro micro-imaging" using the IncuCyte system. Cell viability was measured using the CellTiter 96 Assay. Apoptosis was determined by Caspase-Glo 3/7, 8 and 9 assays. The components of the apoptotic cascade were characterized by western blot analysis. N-t-boc-Daidzein was able to significantly inhibit cell growth and decrease cell viability of OCSC as well as mOCC cells in a dose and time dependent maner. This effect was due to the induction of apoptosis, which is characterized by caspase activation, XIAP and AKT degradation, and mitochondrial depolarization. This study describes a novel compound that can target the OCSCs. These findings may provide vital aide in improving overall survival in patients with EOC.

  10. Abdominal applications of 3.0-T MR imaging: comparative review versus a 1.5-T system.

    PubMed

    Choi, Jin-Young; Kim, Myeong-Jin; Chung, Yong Eun; Kim, Ji Youn; Jones, Alun C; de Becker, Jan; van Cauteren, Marc

    2008-01-01

    With the development of dedicated receiver coils and increased gradient performance, 3.0-T magnetic resonance (MR) systems are gaining wider acceptance in clinical practice. The expected twofold increase in signal-to-noise ratio (SNR) compared with that of 1.5-T MR systems may help improve spatial resolution or increase temporal resolution when used with parallel acquisition techniques. Several issues must be considered when applying 3.0-T MR in the abdomen, including the alteration of the radiofrequency field and relaxation time, increase in energy deposition and susceptibility effects, and problems associated with motion artifacts. For the evaluation of liver lesions, higher SNR and greater resolution achieved with the 3.0-T system could translate into better detection of malignant lesions on T2-weighted images obtained with adjusted imaging parameters. For the evaluation of pancreatic and biliary diseases, high-resolution T2-weighted imaging using single-shot turbo spin-echo sequences is useful; improvement in SNR was noticeable on two-dimensional MR cholangiopancreatographic images. For the preoperative imaging of rectal cancer, a single-shot sequence is useful for dramatically decreasing imaging time while maintaining image quality. Substantial modification of examination protocols, with optimized imaging parameters and sequence designs along with ongoing development of hardware, could contribute to an increased role of the 3.0-T system for abdominal MR examinations.

  11. Nitric Acid and Water Extraction by T2EHDGA in n -Dodecane

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Campbell, Emily L.; Holfeltz, Vanessa E.; Hall, Gabriel B.

    Liquid-liquid distribution behavior of nitric acid (HNO3) and water by a diglycolamide ligand, N,N,N',N'-tetra-2-ethylhexyldiglycolamide (T2EHDGA) into n-dodecane diluent was investigated. Spectroscopic FTIR and NMR characterization of the organic extraction solutions indicate T2EHDGA carbonyl coordinates HNO3 and progressively aggregates at high acid conditions. Water extraction increases in the presence of HNO3. The experimentally observed distribution of HNO3 was modeled using the computer program, SXLSQI. The results indicated that the formation of two organic phase species—HNO3·T2EHDGA and (HNO3)2·T2EHDGA—satisfactory describes the acid transport behavior. Temperature dependent solvent extraction studies allowed for determination of thermodynamic extraction constants and ΔH and ΔS parameters for themore » corresponding extractive processes.« less

  12. Local staging and assessment of colon cancer with 1.5-T magnetic resonance imaging

    PubMed Central

    Blake, Helena; Jeyadevan, Nelesh; Abulafi, Muti; Swift, Ian; Toomey, Paul; Brown, Gina

    2016-01-01

    Objective: The aim of this study was to assess the accuracy of 1.5-T MRI in the pre-operative local T and N staging of colon cancer and identification of extramural vascular invasion (EMVI). Methods: Between 2010 and 2012, 60 patients with adenocarcinoma of the colon were prospectively recruited at 2 centres. 55 patients were included for final analysis. Patients received pre-operative 1.5-T MRI with high-resolution T2 weighted, gadolinium-enhanced T1 weighted and diffusion-weighted images. These were blindly assessed by two expert radiologists. Accuracy of the T-stage, N-stage and EMVI assessment was evaluated using post-operative histology as the gold standard. Results: Results are reported for two readers. Identification of T3 disease demonstrated an accuracy of 71% and 51%, sensitivity of 74% and 42% and specificity of 74% and 83%. Identification of N1 disease demonstrated an accuracy of 57% for both readers, sensitivity of 26% and 35% and specificity of 81% and 74%. Identification of EMVI demonstrated an accuracy of 74% and 69%, sensitivity 63% and 26% and specificity 80% and 91%. Conclusion: 1.5-T MRI achieved a moderate accuracy in the local evaluation of colon cancer, but cannot be recommended to replace CT on the basis of this study. Advances in knowledge: This study confirms that MRI is a viable alternative to CT for the local assessment of colon cancer, but this study does not reproduce the very high accuracy reported in the only other study to assess the accuracy of MRI in colon cancer staging. PMID:27226219

  13. Modified vs. standard D2 lymphadenectomy in distal subtotal gastrectomy for locally advanced gastric cancer patients under 70 years of age.

    PubMed

    Zhang, Chun-Dong; Zong, Liang; Ning, Fei-Long; Zeng, Xian-Tao; Dai, Dong-Qiu

    2018-01-01

    The present study was conducted to investigate the prognosis and survival of patients with locally advanced gastric cancer who underwent distal subtotal gastrectomy with modified D2 (D1+) and D2 lymphadenectomy, under 70 years of age. The five-year overall survival rates of 390 patients were compared between those receiving D1+ and D2 lymphadenectomy. Univariate and multivariate analyses were used to identify factors that correlated with prognosis and lymph node metastasis. Tumor size (P=0.039), pT stage (P=0.011), pN stage (P<0.001), and lymphadenectomy (P=0.004) were identified as independent prognostic factors. Furthermore, tumor size (P=0.022), pT stage (P=0.012), and lymphadenectomy (P=0.028) were proven as independent factors predicting lymph node metastasis. In conclusion, cancers of larger size, higher pT stage, and with D1+ lymphadenectomy had a higher risk of lymph node metastasis. Standard D2 lymphadenectomy removes sufficient lymph nodes to improve staging accuracy and survival. Therefore, D2 lymphanectomy is recommended in distal subtotal gastrectomy for locally advanced gastric cancer, especially for cancers of larger size and higher pT stage.

  14. Non-invasive estimation of prostate cancer aggressiveness using diffusion-weighted MRI and 3D proton MR spectroscopy at 3.0T.

    PubMed

    Thörmer, Gregor; Otto, Josephin; Horn, Lars-Christian; Garnov, Nikita; Do, Minh; Franz, Toni; Stolzenburg, Jens-Uwe; Moche, Michael; Kahn, Thomas; Busse, Harald

    2015-01-01

    Clinical management of prostate cancer increasingly aims to distinguish aggressive types that require immediate and radical treatment from indolent tumors that are candidates for watchful waiting. This requires reliable and reproducible parameters to effectively control potential cancer progression. Magnetic resonance imaging (MRI) may provide a non-invasive means for this purpose. To assess the value of diffusion-weighted imaging and proton MR spectroscopy for the prediction of prostate cancer (PCa) aggressiveness. In 39 of 64 consecutive patients who underwent endorectal 3-T MRI prior to radical prostatectomy, prostate specimens were analyzed as whole-mount step sections. Apparent diffusion coefficient (ADC), normalized ADC (nADC: tumor/healthy tissue), choline/citrate (CC), and (choline + creatine)/citrate (CCC) ratios were correlated with Gleason scores (GS) from histopathological results. The power to discriminate low (GS ≤ 6) from higher-risk (GS ≥ 7) tumors was assessed with receiver operating characteristics (area under the curve [AUC]). Resulting threshold values were used by a blinded reader to distinguish between aggressive and indolent tumors. Ninety lesions (1 × GS = 5, 41 × GS = 6, 36 × GS = 7, 12 × GS = 8) were considered. nADC (AUC = 0.90) showed a higher discriminatory power than ADC (AUC = 0.79). AUC for CC and CCC were 0.73 and 0.82, respectively. Using either nADC < 0.46 or CCC > 1.3, as well as both criteria for aggressive PCa, the reader correctly identified aggressive and indolent tumors in 31 (79%), 28 (72%), and 33 of 39 patients (85%), respectively. Predictions of tumor aggressiveness from TRUS-guided biopsies were correct in 27 of 36 patients (75%). The combination of a highly sensitive normalized ADC with a highly specific CCC was found to be well suited to prospectively estimate PCa aggressiveness with a similar diagnostic accuracy as biopsy results. © The Foundation

  15. Enhancing adoptive cancer immunotherapy with Vγ22 T cells through pulse zoledronate stimulation.

    PubMed

    Nada, Mohanad H; Wang, Hong; Workalemahu, Grefachew; Tanaka, Yoshimasa; Morita, Craig T

    2017-01-01

    Human γδ T cells expressing Vγ22 T cell receptors monitor foreign- and self-prenyl pyrophosphate metabolites in isoprenoid biosynthesis to mediate immunity to microbes and tumors. Adoptive immunotherapy with Vγ22 T cells has been used to treat cancer patients with partial and complete remissions. Most clinical trials and preclinical studies have used continuous zoledronate exposure to expand Vγ22 cells where zoledronate is slowly diluted over the course of the culture. Zoledronate inhibits farnesyl diphosphate synthase (FDPS) in monocytes causing isopentenyl pyrophosphate to accumulate that then stimulates Vγ22 cells. Because zoledronate inhibition of FDPS is also toxic for T cells, we hypothesized that a short period of exposure would reduce T cell toxicity but still be sufficient for monocytes uptake. Additionally, IL-15 increases the anti-tumor activity of murine αβ T cells in mice but its effect on the in vivo anti-tumor activity of human Vγ22 cells has not been assessed. Human Vγ22 T cells were expanded by pulse or continuous zoledronate stimulation with IL-2 or IL-15. Expanded Vγ22 cells were tested for their expression of effector molecules and killing of tumor cells as well as their in vivo control of human prostate cancer tumors in immunodeficient NSG mice. Pulse zoledronate stimulation with either IL-2 or IL-15 resulted in more uniform expansion of Vγ22 cells with higher purity and cell numbers as compared with continuous exposure. The Vγ22 cells had higher levels of CD107a and perforin and increased tumor cytotoxicity. Adoptive immunotherapy with Vγ22 cells derived by pulse stimulation controlled human PC-3 prostate cancer tumors in NSG mice significantly better than those derived by continuous stimulation, halting tumor growth. Although pulse zoledronate stimulation with IL-15 preserved early memory subsets, adoptive immunotherapy with IL-15-derived Vγ22 cells equally inhibited PC-3 tumor growth as those

  16. Phenotype and function of T cells infiltrating visceral metastases from gastrointestinal cancers and melanoma: implications for adoptive cell transfer therapy.

    PubMed

    Turcotte, Simon; Gros, Alena; Hogan, Katherine; Tran, Eric; Hinrichs, Christian S; Wunderlich, John R; Dudley, Mark E; Rosenberg, Steven A

    2013-09-01

    Adoptive cell transfer of tumor-infiltrating lymphocytes (TILs) can mediate cancer regression in patients with metastatic melanoma, but whether this approach can be applied to common epithelial malignancies remains unclear. In this study, we compared the phenotype and function of TILs derived from liver and lung metastases from patients with gastrointestinal (GI) cancers (n = 14) or melanoma (n = 42). Fewer CD3(+) T cells were found to infiltrate GI compared with melanoma metastases, but the proportions of CD8(+) cells, T cell differentiation stage, and expression of costimulatory molecules were similar for both tumor types. Clinical-scale expansion up to ~50 × 10(9) T cells on average was obtained for all patients with GI cancer and melanoma. From GI tumors, however, TIL outgrowth in high-dose IL-2 yielded 22 ± 1.4% CD3(+)CD8(+) cells compared with 63 ± 2.4% from melanoma (p < 0.001). IFN-γ ELISA demonstrated MHC class I-mediated reactivity of TIL against autologous tumor in 5 of 7 GI cancer patients tested (9% of 188 distinct TIL cultures) and in 9 of 10 melanoma patients (43% of 246 distinct TIL cultures). In these assays, MHC class I-mediated up-regulation of CD137 (4-1BB) expression on CD8(+) cells suggested that 0-3% of TILs expanded from GI cancer metastases were tumor-reactive. This study implies that the main challenge to the development of TIL adoptive cell transfer for metastatic GI cancers may not be the in vitro expansion of bulk TILs, but the ability to select and enrich for tumor-reactive T cells.

  17. Phenotype and Function of T Cells Infiltrating Visceral Metastases from Gastrointestinal Cancers and Melanoma: Implications for Adoptive Cell Transfer Therapy

    PubMed Central

    Turcotte, Simon; Gros, Alena; Hogan, Katherine; Tran, Eric; Hinrichs, Christian S.; Wunderlich, John R.; Dudley, Mark E.

    2013-01-01

    Adoptive cell transfer of tumor-infiltrating lymphocytes (TILs) can mediate cancer regression in patients with metastatic melanoma, but whether this approach can be applied to common epithelial malignancies remains unclear. In this study, we compared the phenotype and function of TILs derived from liver and lung metastases from patients with gastrointestinal (GI) cancers (n = 14) or melanoma (n = 42). Fewer CD3+ T cells were found to infiltrate GI compared with melanoma metastases, but the proportions of CD8+ cells, T cell differentiation stage, and expression of costimulatory molecules were similar for both tumor types. Clinical-scale expansion up to ∼50 × 109 T cells on average was obtained for all patients with GI cancer and melanoma. From GI tumors, however, TIL outgrowth in high-dose IL-2 yielded 22 ± 1.4% CD3+CD8+ cells compared with 63 ± 2.4% from melanoma (p < 0.001). IFN-γ ELISA demonstrated MHC class I–mediated reactivity of TIL against autologous tumor in 5 of 7 GI cancer patients tested (9% of 188 distinct TIL cultures) and in 9 of 10 melanoma patients (43% of 246 distinct TIL cultures). In these assays, MHC class I–mediated up-regulation of CD137 (4-1BB) expression on CD8+ cells suggested that 0–3% of TILs expanded from GI cancer metastases were tumor-reactive. This study implies that the main challenge to the development of TIL adoptive cell transfer for metastatic GI cancers may not be the in vitro expansion of bulk TILs, but the ability to select and enrich for tumor-reactive T cells. PMID:23904171

  18. Partial Nephrectomy Versus Radical Nephrectomy for Clinical T1b and T2 Renal Tumors: A Systematic Review and Meta-analysis of Comparative Studies.

    PubMed

    Mir, Maria Carmen; Derweesh, Ithaar; Porpiglia, Francesco; Zargar, Homayoun; Mottrie, Alexandre; Autorino, Riccardo

    2017-04-01

    .001), lower likelihood of postoperative onset of chronic kidney disease (RR 0.36; p<0.001), and lower decline in eGFR (WMD -8.6ml/min; p<0.001). The PN group had a lower likelihood of tumor recurrence (OR 0.6; p<0.001), cancer-specific mortality (OR 0.58; p=0.001), and all-cause mortality (OR 0.67; p=0.005). Four studies compared PN (n=212) to RN (n=1792) in the specific case of T2 tumors (>7cm). In this subset of patients, the estimated blood loss was higher for PN (WMD 107.6ml; p<0.001), as was the likelihood of complications (RR 2.0; p<0.001). Both the recurrence rate (RR 0.61; p=0.004) and cancer-specific mortality (RR 0.65; p=0.03) were lower for PN. PN is a viable treatment option for larger renal tumors, as it offers acceptable surgical morbidity, equivalent cancer control, and better preservation of renal function, with potential for better long-term survival. For T2 tumors, PN use should be more selective, and specific patient and tumor factors should be considered. Further investigation, ideally in a prospective randomized fashion, is warranted to better define the role of PN in this challenging clinical scenario. We performed a cumulative analysis of the literature to determine the best treatment option in cases of localized kidney tumor of higher clinical stage (T1b and T2, as based on preoperative imaging). Our findings suggest that removing only the tumor and saving the kidney might be an effective treatment modality in terms of cancer control, with the advantage of preserving the kidney function. However, a higher risk of perioperative complications should be taken into account when facing larger tumors (clinical stage T2) with kidney-sparing surgery. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  19. [Hypothyroidism incidence after multimodal treatment for laryngeal cancer].

    PubMed

    Ortega-Gutiérrez, César; Luna-Ortiz, Kuauhyama; Villavicencio-Valencia, Verónica; Herrera Gómez, Angel; Téllez-Palacios, Daniela; Contreras-Buendía, Marlen

    2012-01-01

    Hypothyroidism following total laryngectomy or radiotherapy treatment for laryngeal cancer is not a rare event, especially in advanced stages. There are no reports on the incidence of hypothyroidism in patients who received chemotherapy and radiotherapy. The objective of this study is to determine the incidence of thyroid dysfunction in a group of patients with laryngeal cancer who underwent surgery as sole treatment, total laryngectomy or radiotherapy alone, and patients with combined treatment: surgery plus radiotherapy, concomitant chemoradiation therapy and chemoradiation therapy plus salvage surgery. A prospective study of patients diagnosed with laryngeal cancer whose serum TSH and T4 levels were evaluated in a serial fashion. 70 patients with laryngeal cancer were studied; the average age at diagnosis was 70.2 years. Male patients were more affected, with a men-women ratio of 3.6:1. Glottic localization was the most frequent (44%). 64% of tumors were locally advanced carcinomas and 51% received multimodal treatment. 45 patients (63%) were diagnosed with hypothyroidism; 49% of the patients with subclinical hypothyroidism, and 51% with clinical hypothyroidism. Hypothyroidism is a complication following treatment for laryngeal cancer. It is recommended to evaluate the thyroid function periodically for timely detection.

  20. Development of a high risk pancreatic screening clinic using 3.0 T MRI.

    PubMed

    Barnes, Chad A; Krzywda, Elizabeth; Lahiff, Shannon; McDowell, Dena; Christians, Kathleen K; Knechtges, Paul; Tolat, Parag; Hohenwalter, Mark; Dua, Kulwinder; Khan, Abdul H; Evans, Douglas B; Geurts, Jennifer; Tsai, Susan

    2018-01-01

    Selective screening for pancreatic cancer (PC) has been proposed. We describe the establishment of a comprehensive multidisciplinary screening program using 3.0 T MRI. Criteria for screening included the presence of PC in: ≥ 2 first degree relatives (FDR), 1 FDR and 1 s degree relative (SDR), ≥ 3 any degree relatives (ADR), or any known hereditary cancer syndrome with increased PC risk. Imaging with 3.0 T MRI was performed routinely and endoscopic ultrasound was used selectively. Screening was completed in 75 patients (pts). Hereditary cancer syndromes were present in 42 (56%) of the 75 pts: BRCA2 (18), ATM (8), BRCA1 (6), CDKN2A (4), PALB2 (3), Lynch (2), and Peutz-Jeghers (1). A family history of PC was present in ≥ 2 FDR in 12 (16%) pts, 1 FDR and 1 SDR in 5 (7) pts, and ≥ 3 ADR in 16 (21%) pts. Of the 65 pts who received screening MRI, 28 (43%) pts had pancreatic cystic lesions identified, including 1 (1%) patient in whom a cholangiocarcinoma was diagnosed as well. No patient underwent surgical resection. Using a 3.0 T MRI to screen patients at high risk for developing PC identified radiographic abnormalities in 43% of patients, which were stable on subsequent surveillance. Specific guidelines for the frequency of surveillance and indications for surgery remain areas of active investigation as the global experience with high risk screening continues to mature.

  1. Breast cancer detection using double reading of unenhanced MRI including T1-weighted, T2-weighted STIR, and diffusion-weighted imaging: a proof of concept study.

    PubMed

    Trimboli, Rubina M; Verardi, Nicola; Cartia, Francesco; Carbonaro, Luca A; Sardanelli, Francesco

    2014-09-01

    The purpose of this study was to investigate the diagnostic performance of unenhanced MRI in detecting breast cancer and to assess the impact of double reading. A total of 116 breasts of 67 women who were 36-89 years old were studied at 1.5 T using an unenhanced protocol including axial T1-weighted gradient-echo, T2-weighted STIR, and echo-planar diffusion-weighted imaging (DWI). Two blinded readers (R1 and R2) independently evaluated unenhanced images using the BIRADS scale. A combination of pathology and negative follow-up served as the reference standard. McNemar and kappa statistics were used. Per-breast cancer prevalence was 37 of 116 (32%): 30 of 37 (81%) invasive ductal carcinoma, five of 37 (13%) ductal carcinoma in situ, and two of 37 (6%) invasive lobular carcinoma. Per-breast sensitivity of unenhanced MRI was 29 of 37 (78%) for R1, 28 of 37 (76%) for R2, and 29 of 37 (78%) for double reading. Specificity was 71 of 79 (90%) for both R1 and R2 and 69 of 79 (87%) for double reading. Double reading did not provide a significant increase in sensitivity. Interobserver agreement was almost perfect (Cohen κ = 0.873). An unenhanced breast MRI protocol composed of T1-weighted gradient echo, T2-weighted STIR, and echo-planar DWI enabled breast cancer detection with sensitivity of 76-78% and specificity of 90% without a gain in sensitivity from double reading.

  2. Influence of Preoperative Chemoradiotherapy on the Surgical Strategy According to the Clinical T Stage of Patients With Rectal Cancer

    PubMed Central

    Park, In Ja; Lee, Jong Lyul; Yoon, Yong Sik; Kim, Chan Wook; Lim, Seok-Byung; Lee, Jong Seok; Park, Seong Ho; Park, Jin Hong; Kim, Jong Hoon; Yu, Chang Sik; Kim, Jin Cheon

    2015-01-01

    Abstract The aim of this study was to evaluate the pathologic responses and changes to surgical strategies following preoperative chemoradiotherapy (PCRT) in rectal cancer patients according to their clinical T stage (cT). The use of PCRT has recently been extended to less advanced disease. The authors enrolled 650 patients with cT2 to 4 mid and low rectal cancer who received both PCRT and surgical resection. The rate of total regression and the proportion of local excision were compared according to the cT category. The 3-year recurrence-free survival (RFS) rate was compared using the log-rank test according to patient cT category, pathologic stage, and type of surgical treatment. Patients with cT2 were older (P = 0.001), predominately female (P = 0.028), and had low-lying rectal cancer (P = 0.008). Pathologic total regression was achieved most frequently in cT2 patients (54% of cT2 versus 17.6% of cT3 versus 8.2% of cT4; P < 0.001). Local excision was performed on 42 cT2 (42%) and 24 cT3 (5.2%) patients (P < 0.001). The 3-year RFS rates differed according to both cT (P < 0.001) and ypT stage (P < 0.001). Among patients with ypT0 to 1 disease, the 3-year RFS did not differ according to the type of surgical treatment received (P = 0.5). Total regression of the primary tumor and a change in the surgical strategy after PCRT are most commonly seen in cT2 disease. Although PCRT is not generally indicated for cT2 rectal cancer, optimal surgical treatment may be achieved with the tailored use of PCRT. PMID:26717384

  3. Evidence supporting contemporary post-operative radiation therapy (PORT) using linear accelerators in N2 lung cancer.

    PubMed

    Patel, Suchit H; Ma, Yan; Wernicke, A Gabriella; Nori, Dattatreyudu; Chao, K S C; Parashar, Bhupesh

    2014-05-01

    Post-operative radiotherapy (PORT) treatment for lung cancer declined since a meta-analysis failed to show benefit in patients with N2 disease. Because several included studies employed outmoded radiation planning and delivery techniques, we sought to determine whether PORT with modern technology benefits patients with N2 disease. We conducted searches of the published literature. For inclusion, studies must have included patients with stage III-N2 lung cancer treated with PORT using only linear accelerators, used a control group that did not receive PORT, and reported outcome data for overall survival (OS). Prospective and retrospective analyses were included. Exclusion criteria were the use of cobalt devices or orthovoltage radiation. Data were evaluated with random-effects models. Three prospective and eight retrospective studies were included. The PORT and no-PORT groups included 1368 and 1360 patients, respectively. The PORT group had significantly improved OS over the no-PORT group (hazard ratio [HR] = 0.77, 95% confidence interval [CI] 0.62-0.96, P = 0.020). Locoregional recurrence-free survival (LRFS) in 10 studies for which data was available was also improved in the PORT group (HR = 0.51, CI 0.41-0.65, P < 0.001). PORT was associated with significantly lower risk of death and locoregional recurrence in patients with N2 lung cancer. Our study was limited by lack of access to individual patient data, which would have enabled more detailed analyses. Regardless, data thus far suggest PORT may be associated with a survival benefit. Given a lack of large-scale prospective data, clinical trials evaluating PORT with modern technology are warranted. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  4. Methylenetetrahydrofolate reductase C677T polymorphism in patients with gastric and colorectal cancer in a Korean population

    PubMed Central

    2010-01-01

    Background This study was designed to investigate an association between the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and the risk of gastric and colorectal cancer in the Korean population. Methods We conducted a population-based large-scale case-control study involving 2,213 patients with newly diagnosed gastric cancer, 1,829 patients with newly diagnosed colorectal cancer, and 1,700 healthy controls. Genotyping was performed with peripheral blood DNA for MTHFR C677T polymorphisms. The statistical significance was estimated by logistic regression analysis. Results The MTHFR C677T frequencies of CC, CT, and TT genotypes were 35.2%, 47.5%, and 17.3% among stomach cancer, 34%, 50.5%, and 15.5% in colorectal cancer, and 31.8%, 50.7%, and 17.5% in the controls, respectively. The MTHFR 677TT genotype showed a weak opposite association with colorectal cancer compared to the homozygous CC genotype [adjusted age and sex odds ratio (OR) = 0.792, 95% confidence interval (CI) = 0.638-0.984, P = 0.035]. Subjects with the MTHFR 677CT showed a significantly reduced risk of gastric cancer compared whose with the 677CC genotype (age- and sex-adjusted OR = 0.810; 95% CI = 0.696-0.942, P = 0.006). We also observed no significant interactions between the MTHFR C677T polymorphism and smoking or drinking in the risk of gastric and colorectal cancer. Conclusions The T allele was found to provide a weak protective association with gastric cancer and colorectal cancer. PMID:20504332

  5. An Acquired HER2T798I Gatekeeper Mutation Induces Resistance to Neratinib in a Patient with HER2 Mutant-Driven Breast Cancer.

    PubMed

    Hanker, Ariella B; Brewer, Monica Red; Sheehan, Jonathan H; Koch, James P; Sliwoski, Gregory R; Nagy, Rebecca; Lanman, Richard; Berger, Michael F; Hyman, David M; Solit, David B; He, Jie; Miller, Vincent; Cutler, Richard E; Lalani, Alshad S; Cross, Darren; Lovly, Christine M; Meiler, Jens; Arteaga, Carlos L

    2017-06-01

    We report a HER2 T798I gatekeeper mutation in a patient with HER2 L869R -mutant breast cancer with acquired resistance to neratinib. Laboratory studies suggested that HER2 L869R is a neratinib-sensitive, gain-of-function mutation that upon dimerization with mutant HER3 E928G , also present in the breast cancer, amplifies HER2 signaling. The patient was treated with neratinib and exhibited a sustained partial response. Upon clinical progression, HER2 T798I was detected in plasma tumor cell-free DNA. Structural modeling of this acquired mutation suggested that the increased bulk of isoleucine in HER2 T798I reduces neratinib binding. Neratinib blocked HER2-mediated signaling and growth in cells expressing HER2 L869R but not HER2 L869R/T798I In contrast, afatinib and the osimertinib metabolite AZ5104 strongly suppressed HER2 L869R/T798I -induced signaling and cell growth. Acquisition of HER2 T798I upon development of resistance to neratinib in a breast cancer with an initial activating HER2 mutation suggests HER2 L869R is a driver mutation. HER2 T798I -mediated neratinib resistance may be overcome by other irreversible HER2 inhibitors like afatinib. Significance: We found an acquired HER2 gatekeeper mutation in a patient with HER2 -mutant breast cancer upon clinical progression on neratinib. We speculate that HER2 T798I may arise as a secondary mutation following response to effective HER2 tyrosine kinase inhibitors (TKI) in other cancers with HER2 -activating mutations. This resistance may be overcome by other irreversible HER2 TKIs, such as afatinib. Cancer Discov; 7(6); 575-85. ©2017 AACR. This article is highlighted in the In This Issue feature, p. 539 . ©2017 American Association for Cancer Research.

  6. Worldwide Esophageal Cancer Collaboration: clinical staging data.

    PubMed

    Rice, T W; Apperson-Hansen, C; DiPaola, L M; Semple, M E; Lerut, T E M R; Orringer, M B; Chen, L-Q; Hofstetter, W L; Smithers, B M; Rusch, V W; Wijnhoven, B P L; Chen, K N; Davies, A R; D'Journo, X B; Kesler, K A; Luketich, J D; Ferguson, M K; Räsänen, J V; van Hillegersberg, R; Fang, W; Durand, L; Allum, W H; Cecconello, I; Cerfolio, R J; Pera, M; Griffin, S M; Burger, R; Liu, J-F; Allen, M S; Law, S; Watson, T J; Darling, G E; Scott, W J; Duranceau, A; Denlinger, C E; Schipper, P H; Ishwaran, H; Blackstone, E H

    2016-10-01

    To address uncertainty of whether clinical stage groupings (cTNM) for esophageal cancer share prognostic implications with pathologic groupings after esophagectomy alone (pTNM), we report data-simple descriptions of patient characteristics, cancer categories, and non-risk-adjusted survival-for clinically staged patients from the Worldwide Esophageal Cancer Collaboration (WECC). Thirty-three institutions from six continents submitted data using variables with standard definitions: demographics, comorbidities, clinical cancer categories, and all-cause mortality from first management decision. Of 22,123 clinically staged patients, 8,156 had squamous cell carcinoma, 13,814 adenocarcinoma, 116 adenosquamous carcinoma, and 37 undifferentiated carcinoma. Patients were older (62 years) men (80%) with normal body mass index (18.5-25 mg/kg 2 , 47%), little weight loss (2.4 ± 7.8 kg), 0-1 ECOG performance status (67%), and history of smoking (67%). Cancers were cT1 (12%), cT2 (22%), cT3 (56%), cN0 (44%), cM0 (95%), and cG2-G3 (89%); most involved the distal esophagus (73%). Non-risk-adjusted survival for squamous cell carcinoma was not distinctive for early cT or cN; for adenocarcinoma, it was distinctive for early versus advanced cT and for cN0 versus cN+. Patients with early cancers had worse survival and those with advanced cancers better survival than expected from equivalent pathologic categories based on prior WECC pathologic data. Thus, clinical and pathologic categories do not share prognostic implications. This makes clinically based treatment decisions difficult and pre-treatment prognostication inaccurate. These data will be the basis for the 8th edition cancer staging manuals following risk adjustment for patient characteristics, cancer categories, and treatment characteristics and should direct 9th edition data collection. © 2016 International Society for Diseases of the Esophagus.

  7. Preoperative neo-adjuvant therapy for curable rectal cancer--reaching a consensus 2008.

    PubMed

    Scott, N A; Susnerwala, S; Gollins, S; Myint, A Sun; Levine, E

    2009-03-01

    Our aim was to determine the range of neo-adjuvant therapy the multidisciplinary team (MDT) currently offers patients with curable (M(0)) rectal cancer. A senior oncologist from each of the four oncology centres in north Wales and the north-west of England (approximate target population 8 million - Glan Clwyd, Clatterbridge, Christie and Preston) reviewed his/her understanding of the current evidence of neo-adjuvant therapy in rectal cancer. Then a representative from each centre was asked to identify which of three neo-adjuvant options (no neo-adjuvant therapy, short-course radiotherapy 25 Gy over five fractions and long-course chemoradiotherapy) he/she would use for a rectal cancer in the upper, middle or lower third of the rectum staged by magnetic resonance imaging as being T(2)-T(4) and/or N(0)-N(2). In all cases of locally advanced rectal cancer (T(3a) N(1)-T(4)), oncologists from the four oncology centres recommended long-course chemoradiotherapy before rectal resection. This consensus was maintained for cases of lower third T(3a) N(0) cancers. Thereafter, the majority of patients with rectal cancer are offered adjuvant short-course radiotherapy. Neo-adjuvant therapy is less likely to be offered if the tumour is early (T(2), N(0)) and/or situated in the upper third of the rectum.

  8. t-Darpp overexpression in HER2-positive breast cancer confers a survival advantage in lapatinib.

    PubMed

    Christenson, Jessica L; Denny, Erin C; Kane, Susan E

    2015-10-20

    Drug resistance is a major barrier to successful cancer treatment. For patients with HER2-positive breast cancer who initially respond to therapy, the majority develop resistance within one year of treatment. Patient outcomes could improve significantly if we can find and exploit common mechanisms of acquired resistance to different targeted therapies. Overexpression of t-Darpp, a truncated form of the dual kinase/phosphatase inhibitor Darpp-32, has been linked to acquired resistance to trastuzumab, a front-line therapy for HER2-positive breast cancer. Darpp-32 reverses t-Darpp's effect on trastuzumab resistance. In this study, we examined whether t-Darpp could be involved in resistance to lapatinib, another HER2-targeted therapeutic. Lapatinib-resistant SKBR3 cells (SK/LapR) showed a marked change in the Darpp-32:t-Darpp ratio toward a predominance of t-Darpp. Overexpression of t-Darpp alone was not sufficient to confer lapatinib resistance, but cells that overexpress t-Darpp partially mimicked the molecular resistance phenotype observed in SK/LapR cells exposed to lapatinib. SK/LapR cells failed to down-regulate Survivin and failed to induce BIM accumulation in response to lapatinib; cells overexpressing t-Darpp exhibited only the failed BIM accumulation. t-Darpp knock-down reversed this phenotype. Using a fluorescence-based co-culture system, we found that cells overexpressing t-Darpp formed colonies in lapatinib within 3-4 weeks, whereas parental cells in the same co-culture did not. Overall, t-Darpp appears to mediate a survival advantage in lapatinib, possibly linked to failed lapatinib-induced BIM accumulation. t-Darpp might also be relevant to acquired resistance to other cancer drugs that rely on BIM accumulation to induce apoptosis.

  9. Interleukin 2 and interleukin 10 function synergistically to promote CD8+ T cell cytotoxicity, which is suppressed by regulatory T cells in breast cancer.

    PubMed

    Li, Xiaogang; Lu, Ping; Li, Bo; Zhang, Wanfu; Yang, Rong; Chu, Yan; Luo, Kaiyuan

    2017-06-01

    The precise role of interleukin (IL)-10 in breast cancer is not clear. Previous studies suggested a tumor-promoting role of IL-10 in breast cancer, whereas recent discoveries that IL-10 activated and expanded tumor-resident CD8 + T cells challenged the traditional view. Here, we investigated the role of IL-10 in HLA-A2-positive breast cancer patients with Grade III, Stage IIA or IIB in-situ and invasive ductal carcinoma, and compared it with that of IL-2, the canonical CD8 + T cell growth factor. We first observed that breast cancer patients presented higher serum levels of IL-2 and IL-10 than healthy controls. Upon prolonged TCR stimulation, peripheral blood CD8 + T cells from breast cancer patients tended to undergo apoptosis, which could be prevented by the addition of IL-2 and/or IL-10. The cytotoxicity of TCR-activated CD8 + T cells was also enhanced by exogenous IL-2 and/or IL-10. Interestingly, IL-2 and IL-10 demonstrated synergistic effects, since the enhancement in CD8 + T cell function when both cytokines were added was greater than the sum of the improvements mediated by each individual cytokine. IL-10 by itself could not promote the proliferation of CD8 + T cells but could significantly enhance IL-2-mediated promotion of CD8 + T cell proliferation. In addition, the cytotoxicity of tumor-infiltrating CD8 + T cells in breast tumor was elevated when both IL-2 and IL-10 were present but not when either one was absent. This synergistic effect was stopped by CD4 + CD25 + regulatory T cells (Treg), which depleted IL-2 in a cell number-dependent manner. Together, these results demonstrated that IL-2 and IL-10 could work synergistically to improve the survival, proliferation, and cytotoxicity of activated CD8 + T cells, an effect suppressible by CD4 + CD25 + Treg cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Polaronic transport and thermoelectricity in Fe 1 – x Co x Sb 2 S 4 ( x = 0 , 0.1, and 0.2)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Liu, Yu; Kang, Chang -Jong; Stavitski, Eli

    Here, we report a study of Co-doped berthierite Fe 1–xCo xSb 2S 4 (x=0, 0.1, and 0.2). The alloy series of Fe 1–xCo xSb 2S 4 crystallize in an orthorhombic structure with the Pnma space group, similar to FeSb 2, and show semiconducting behavior. The large discrepancy between activation energy for conductivity, E ρ (146 ~270meV), and thermopower, E S (47 ~108 meV), indicates the polaronic transport mechanism. Bulk magnetization and heat-capacity measurements of pure FeSb 2S 4 (x=0) exhibit a broad antiferromagnetic transition (T N = 46K) followed by an additional weak transition (T* = 50K). Transition temperatures (Tmore » N and T*) slightly decrease with increasing Co content x. This is also reflected in the thermal conductivity measurement, indicating strong spin-lattice coupling. Fe 1–xCo xSb 2S 4 shows relatively high value of thermopower (up to ~624μVK –1 at 300 K) and thermal conductivity much lower when compared to FeSb 2, a feature desired for potential applications based on FeSb 2 materials.« less

  11. Polaronic transport and thermoelectricity in Fe 1 – x Co x Sb 2 S 4 ( x = 0 , 0.1, and 0.2)

    DOE PAGES

    Liu, Yu; Kang, Chang -Jong; Stavitski, Eli; ...

    2018-04-09

    Here, we report a study of Co-doped berthierite Fe 1–xCo xSb 2S 4 (x=0, 0.1, and 0.2). The alloy series of Fe 1–xCo xSb 2S 4 crystallize in an orthorhombic structure with the Pnma space group, similar to FeSb 2, and show semiconducting behavior. The large discrepancy between activation energy for conductivity, E ρ (146 ~270meV), and thermopower, E S (47 ~108 meV), indicates the polaronic transport mechanism. Bulk magnetization and heat-capacity measurements of pure FeSb 2S 4 (x=0) exhibit a broad antiferromagnetic transition (T N = 46K) followed by an additional weak transition (T* = 50K). Transition temperatures (Tmore » N and T*) slightly decrease with increasing Co content x. This is also reflected in the thermal conductivity measurement, indicating strong spin-lattice coupling. Fe 1–xCo xSb 2S 4 shows relatively high value of thermopower (up to ~624μVK –1 at 300 K) and thermal conductivity much lower when compared to FeSb 2, a feature desired for potential applications based on FeSb 2 materials.« less

  12. Magnetic resonance spectroscopy of the canine brain at 3.0 T and 7.0 T.

    PubMed

    Martin-Vaquero, Paula; da Costa, Ronaldo C; Echandi, Rita L; Sammet, Christina L; Knopp, Michael V; Sammet, Steffen

    2012-08-01

    The purpose of this study was to evaluate the feasibility of proton magnetic resonance spectroscopy (1H MRS) to study the concentration of metabolites in the brain of dogs at 3.0 and 7.0 T. Four healthy male beagles were scanned using 3.0 T and 7.0 T human magnetic resonance imaging (MRI) units. The results obtained showed that all dogs had excellent quality spectra for a small (1 cm3) and large (8 cm3) voxel at 3.0 T, whereas only 2 dogs had high quality spectra at 7.0 T due to insufficient water suppression. 1H MRS at 3.0 T appears to be a reliable method to study metabolite concentrations in the canine brain. The development of more advanced water suppression techniques is necessary to improve the results at 7.0 T. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. Relaxivity of Ferumoxytol at 1.5 T and 3.0 T.

    PubMed

    Knobloch, Gesine; Colgan, Timothy; Wiens, Curtis N; Wang, Xiaoke; Schubert, Tilman; Hernando, Diego; Sharma, Samir D; Reeder, Scott B

    2018-05-01

    The aim of this study was to determine the relaxation properties of ferumoxytol, an off-label alternative to gadolinium-based contrast agents, under physiological conditions at 1.5 T and 3.0 T. Ferumoxytol was diluted in gradually increasing concentrations (0.26-4.2 mM) in saline, human plasma, and human whole blood. Magnetic resonance relaxometry was performed at 37°C at 1.5 T and 3.0 T. Longitudinal and transverse relaxation rate constants (R1, R2, R2*) were measured as a function of ferumoxytol concentration, and relaxivities (r1, r2, r2*) were calculated. A linear dependence of R1, R2, and R2* on ferumoxytol concentration was found in saline and plasma with lower R1 values at 3.0 T and similar R2 and R2* values at 1.5 T and 3.0 T (1.5 T: r1saline = 19.9 ± 2.3 smM; r1plasma = 19.0 ± 1.7 smM; r2saline = 60.8 ± 3.8 smM; r2plasma = 64.9 ± 1.8 smM; r2*saline = 60.4 ± 4.7 smM; r2*plasma = 64.4 ± 2.5 smM; 3.0 T: r1saline = 10.0 ± 0.3 smM; r1plasma = 9.5 ± 0.2 smM; r2saline = 62.3 ± 3.7 smM; r2plasma = 65.2 ± 1.8 smM; r2*saline = 57.0 ± 4.7 smM; r2*plasma = 55.7 ± 4.4 smM). The dependence of relaxation rates on concentration in blood was nonlinear. Formulas from second-order polynomial fittings of the relaxation rates were calculated to characterize the relationship between R1blood and R2 blood with ferumoxytol. Ferumoxytol demonstrates strong longitudinal and transverse relaxivities. Awareness of the nonlinear relaxation behavior of ferumoxytol in blood is important for ferumoxytol-enhanced magnetic resonance imaging applications and for protocol optimization.

  14. Body mass index, waist circumference, type 2 diabetes mellitus and risk of liver cancer for U.S. adults

    PubMed Central

    Campbell, Peter T.; Newton, Christina C.; Freedman, Neal D.; Koshiol, Jill; Alavanja, Michael C.; Beane Freeman, Laura E.; Buring, Julie E.; Chan, Andrew T.; Chong, Dawn Q.; Datta, Mridul; Gaudet, Mia M.; Gaziano, J. Michael; Giovannucci, Edward; Graubard, Barry; Hollenbeck, Albert R.; King, Lindsey; Lee, I-Min; Linet, Martha; Palmer, Julie; Petrick, Jessica L.; Poynter, Jenny N.; Purdue, Mark; Robien, Kim; Rosenberg, Lynn; Sahasrabuddhe, Vikrant; Schairer, Catherine; Sesso, Howard D.; Sigurdson, Alice; Stevens, Victoria L.; Wactowski-Wende, Jean; Zeleniuch-Jacquotte, Anne; Renehan, Andrew G.; McGlynn, Katherine A.

    2016-01-01

    Incidence rates for liver cancer have increased threefold since the mid-1970s in the United States in parallel with increasing trends for obesity and type 2 diabetes mellitus (T2DM). We conducted an analysis of baseline body mass index (BMI), waist circumference (WC), and T2DM with risk of liver cancer. The Liver Cancer Pooling Project maintains harmonized data from 1.57 million adults enrolled in 14 U.S.-based prospective studies. Cox regression estimated hazard ratios (HR) and 95% confidence intervals (CI) adjusted for age, sex, study center, alcohol, smoking, race, and BMI (for WC and T2DM). Stratified analyses assessed whether the BMI-liver cancer associations differed by hepatitis sera-positivity in nested analyses for a subset of cases (n=220) and controls (n=547). After enrollment, 2,162 incident liver cancer diagnoses were identified. BMI, per 5 kg/m2, was associated with higher risks of liver cancer, more so for men (HR: 1.38; 95% CI: 1.30 to 1.46) than women (HR: 1.25; 95% CI: 1.17 to 1.35; p-interaction: 0.02). WC, per 5 cm, was associated with higher risks of liver cancer, approximately equally by sex (overall, HR: 1.08; 95% CI: 1.04 to 1.13). T2DM was associated with higher risk of liver cancer (HR: 2.61; 95% CI: 2.34 to 2.91). In stratified analyses, there was a null association between BMI and liver cancer risk for participants who were sera-positive for hepatitis. This study suggests that high BMI, high WC, and T2DM are associated with higher risks of liver cancer and that the association may differ by status of viral hepatitis infection. PMID:27742674

  15. Double PALB2 and BRCA1/BRCA2 mutation carriers are rare in breast cancer and breast-ovarian cancer syndrome families from the French Canadian founder population.

    PubMed

    Ancot, Frédéric; Arcand, Suzanna L; Mes-Masson, Anne-Marie; Provencher, Diane M; Tonin, Patricia N

    2015-06-01

    French Canadian families with breast cancer and breast-ovarian cancer syndrome harbor specific BRCA1, BRCA2 and PALB2 germline mutations, which have been attributed to common founders. Mutations in these genes confer an increased risk to breast and ovarian cancers, and have been identified to play a role in and directly interact with the common homologous recombination DNA repair pathways. Our previous study described the case of a female diagnosed with breast cancer at 45 years old, who harbored the PALB2:c.2323C>T [p.Q775X] and BRCA2:c.9004G>A [p.E3002K] germline mutations, which have been found to recur in the French Canadian cancer families. As the frequency of double heterozygous carriers of breast-ovarian cancer susceptibility alleles is unknown, and due to the possibility that there may be implications for genetic counseling and management for these carriers, the present study investigated the co-occurrence of BRCA1/BRCA2 and PALB2 mutations in the French Canadian cancer families. The PALB2:c.2323C>T [p.Q775X] mutation, which is the only PALB2 mutation to have been identified in French Canadian cancer families, was screened in 214 breast cancer cases and 22 breast-ovarian cancer cases from 114 BRCA1/BRCA2 mutation-positive French Canadian breast cancer (n=61) and breast-ovarian cancer (n=53) families using a tailored polymerase chain reaction-based TaqMan® SNP Genotyping Assay. No additional PALB2:c.2323C>T [p.Q775X] mutation carriers were identified among the BRCA1/BRCA2 mutation carriers. The results suggest that carriers of the PALB2:c.2323C>T [p.Q775X] mutation rarely co-occur in French Canadian breast cancer and breast-ovarian cancer families harboring BRCA1 or BRCA2 mutations.

  16. Potentially pathogenic germline CHEK2 c.319+2T>A among multiple early-onset cancer families.

    PubMed

    Dominguez-Valentin, Mev; Nakken, Sigve; Tubeuf, Hélène; Vodak, Daniel; Ekstrøm, Per Olaf; Nissen, Anke M; Morak, Monika; Holinski-Feder, Elke; Martins, Alexandra; Møller, Pål; Hovig, Eivind

    2018-01-01

    To study the potential contribution of genes other than BRCA1/2, PTEN, and TP53 to the biological and clinical characteristics of multiple early-onset cancers in Norwegian families, including early-onset breast cancer, Cowden-like and Li-Fraumeni-like syndromes (BC, CSL and LFL, respectively). The Hereditary Cancer Biobank from the Norwegian Radium Hospital was used to identify early-onset BC, CSL or LFL for whom no pathogenic variants in BRCA1/2, PTEN, or TP53 had been found in routine diagnostic DNA sequencing. Forty-four cancer susceptibility genes were selected and analyzed by our in-house designed TruSeq amplicon-based assay for targeted sequencing. Protein- and RNA splicing-dedicated in silico analyses were performed for all variants of unknown significance (VUS). Variants predicted as the more likely to affect splicing were experimentally analyzed by minigene assay. We identified a CSL individual carrying a variant in CHEK2 (c.319+2T>A, IVS2), here considered as likely pathogenic. Out of the five VUS (BRCA2, CDH1, CHEK2, MAP3K1, NOTCH3) tested in the minigene splicing assay, only NOTCH3 c.14090C>T (p.Ser497Leu) showed a significant effect on RNA splicing, notably by inducing partial skipping of exon 9. Among 13 early-onset BC, CSL and LFL patients, gene panel sequencing identified a potentially pathogenic variant in CHEK2 that affects a canonical RNA splicing signal. Our study provides new information on genetic loci that may affect the risk of developing cancer in these patients and their families, demonstrating that genes presently not routinely tested in molecular diagnostic settings may be important for capturing cancer predisposition in these families.

  17. Comparison of endorectal coil and nonendorectal coil T2W and diffusion-weighted MRI at 3 Tesla for localizing prostate cancer: correlation with whole-mount histopathology.

    PubMed

    Turkbey, Baris; Merino, Maria J; Gallardo, Elma Carvajal; Shah, Vijay; Aras, Omer; Bernardo, Marcelino; Mena, Esther; Daar, Dagane; Rastinehad, Ardeshir R; Linehan, W Marston; Wood, Bradford J; Pinto, Peter A; Choyke, Peter L

    2014-06-01

    To compare utility of T2-weighted (T2W) MRI and diffusion-weighted MRI (DWI-MRI) obtained with and without an endorectal coil at 3 Tesla (T) for localizing prostate cancer. This Institutional Review Board-approved study included 20 patients (median prostate-specific antigen, 8.4 ng/mL). Patients underwent consecutive prostate MRIs at 3T, first with a surface coil alone, then with combination of surface, endorectal coils (dual coil) followed by robotic assisted radical prostatectomy. Lesions were mapped at time of acquisition on dual-coil T2W, DWI-MRI. To avoid bias, 6 months later nonendorectal coil T2W, DWI-MRI were mapped. Both MRI evaluations were performed by two readers blinded to pathology with differences resolved by consensus. A lesion-based correlation with whole-mount histopathology was performed. At histopathology 51 cancer foci were present ranging in size from 2 to 60 mm. The sensitivity of the endorectal dual-coil, nonendorectal coil MRIs were 0.76, 0.45, respectively. PPVs for endorectal dual-coil, nonendorectal coil MRI were 0.80, 0.64, respectively. Mean size of detected lesions with nonendorectal coil MRI were larger than those detected by dual-coil MRI (22 mm versus 17.4 mm). Dual-coil prostate MRI detected more cancer foci than nonendorectal coil MRI. While nonendorectal coil MRI is an attractive alternative, physicians performing prostate MRI should be aware of its limitations. Copyright © 2013 Wiley Periodicals, Inc.

  18. Breast cancer, heterocyclic aromatic amines from meat and N-acetyltransferase 2 genotype.

    PubMed

    Delfino, R J; Sinha, R; Smith, C; West, J; White, E; Lin, H J; Liao, S Y; Gim, J S; Ma, H L; Butler, J; Anton-Culver, H

    2000-04-01

    Breast cancer risk has been hypothesized to increase with exposure to heterocyclic aromatic amines (HAAs) formed from cooking meat at high temperature. HAAs require enzymatic activation to bind to DNA and initiate carcinogenesis. N-acetyltransferase 2 (NAT2) enzyme activity may play a role, its rate determined by a polymorphic gene. We examined the effect of NAT2 genetic polymorphisms on breast cancer risk from exposure to meat by cooking method, doneness and estimated HAA [2-amino-1-methyl-6-phenylimidazole[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx)] intake. Women were recruited with suspicious breast masses and questionnaire data were collected prior to biopsy to blind subjects and interviewers to diagnoses. For 114 cases with breast cancer and 280 controls with benign breast disease, NAT2 genotype was determined using allele-specific PCR amplification to detect slow acetylator mutations. HAAs were estimated from interview data on meat type, cooking method and doneness, combined with a quantitative HAA database. Logistic regression models controlled for known risk factors, first including all controls, then 108 with no or low risk (normal breast or no hyperplasia) and finally 149 with high risk (hyperplasia, atypical hyperplasia, complex fibroadenomas). Meat effects were examined within NAT2 strata to assess interactions. We found no association between NAT2 and breast cancer. These Californian women ate more white than red meat (control median 46 versus 8 g/day). There were no significant associations of breast cancer with red meat for any doneness. White meat was significantly protective (>67 versus <26 g/day, OR 0.46, 95% CI 0.23-0.94, P for trend = 0.02), as was chicken, including well done, pan fried and barbecued chicken. MeIQx and DiMeIQx were not associated with breast cancer. A protective effect of PhIP was confounded after controlling for well done chicken

  19. Association between N142D genetic polymorphism of GSTO2 and susceptibility to colorectal cancer.

    PubMed

    Masoudi, Mohammad; Saadat, Iraj; Omidvari, Shahpour; Saadat, Mostafa

    2011-10-01

    Expression pattern analysis has been revealed that glutathione S-transferase omega 2 (GSTO2, a member of class omega) is ubiquitously expressed. Over expression of GSTO2 induced apoptosis. The gene encoding GSTO2 was localized to human chromosome 10q24.3, a region that may harbor gene(s) involved in the developing of colorectal cancer. To investigate the association between GSTO2 N142D genetic polymorphism and susceptibility to colorectal cancer the present study was done. We studied 63 (26 females, 37 males) colorectal cancer patients and 126 (52 females, 74 males) healthy individuals. The control subjects were frequency matched for age and gender with the colorectal cancer group. The genotypes were performed using RFLP-PCR method. The ND and DD genotypes were not associated with risk of colorectal cancer, in comparison with the NN genotype. Family history for cancer in the first degree of relatives significantly differed between cases and controls (P = 0.012). The profiles of GSTO2 genotypes and family history in control and cancerous groups were compared to each other. Subjects with NN genotype and positive family history significantly were at high risk to develop colorectal cancer in comparison with subjects with DD or ND genotypes and negative family history (P = 0.003). Present findings indicating that GSTO2 NN genotype increase the risk of colorectal cancer in persons with positive family history for cancer in the first degree relatives.

  20. Older Patients With Early-stage Breast Cancer: Adjuvant Radiation Therapy and Predictive Factors for Cancer-related Death.

    PubMed

    Nagar, Himanshu; Yan, Weisi; Christos, Paul; Chao, K S Clifford; Nori, Dattatreyudu; Ravi, Akkamma

    2017-06-01

    Studies have shown that older women are undertreated for breast cancer. Few data are available on cancer-related death in elderly women aged 70 years and older with pathologic stage T1a-b N0 breast cancer and the impact of prognostic factors on cancer-related death. The Surveillance, Epidemiology, and End Results (SEER) database was queried for women aged 70 years or above diagnosed with pT1a or pT1b, N0 breast cancer who underwent breast conservation surgery from 1999 to 2003. The Kaplan-Meier survival analysis was performed to evaluate breast cause-specific survival (CSS) and overall survival (OS), and the log-rank test was employed to compare CSS/OS between different groups of interest. Multivariable analysis (MVA), using Cox proportional hazards regression analysis, was performed to evaluate the independent effect of age, race, stage, grade, ER status, and radiation treatment on CSS. Adjusted hazard ratios were calculated from the MVA and reflect the increased risk of breast cancer death. Competing-risks survival regression was also performed to adjust the univariate and multivariable CSS hazard ratios for the competing event of death due to causes other than breast cancer. Patients aged 85 and above had a greater risk of breast cancer death compared with patients aged 70 to 74 years (referent category) (adjusted hazard ratio [HRs]=1.98). Race had no effect on CSS. Patients with stage T1bN0 breast cancer had a greater risk of breast cancer death compared with stage T1aN0 patients (adjusted HR=1.35; P=0.09). ER negative patients had a greater risk of breast cancer death compared with ER positive patients (adjusted HR=1.59; P<0.017). Patients with higher grade tumors had a greater risk of breast cancer death compared with patients with grade 1 tumors (referent category) (adjusted HRs=1.69 and 2.96 for grade 2 and 3, respectively). Patients who underwent radiation therapy had a lower risk of breast cancer death compared with patients who did not (adjusted HR=0

  1. Assessment of family psychosocial functioning in survivors of pediatric cancer using the PAT2.0.

    PubMed

    Gilleland, Jordan; Reed-Knight, Bonney; Brand, Sarah; Griffin, Anya; Wasilewski-Masker, Karen; Meacham, Lillian; Mertens, Ann

    2013-09-01

    This study aimed to examine clinical validity and utility of a screening measure for familial psychosocial risk, the Psychosocial Assessment Tool 2.0 (PAT2.0), among pediatric cancer survivors participating in long-term survivorship care. Caregivers (N=79) completed the PAT2.0 during their child's survivorship appointment. Caregivers also reported on family engagement in outpatient mental health treatment. Medical records were reviewed for treatment history and oncology provider initiated psychology consults. The internal consistency of the PAT2.0 total score in this survivorship sample was strong. Psychology was consulted by the oncology provider to see 53% of participant families, and families seen by psychology had significantly higher PAT2.0 total scores than families without psychology consults. PAT2.0 total scores and corresponding subscales were higher for patients, parents, and siblings enrolled in outpatient mental health services since treatment completion. Results were consistent with psychosocial risk categories presented within the Pediatric Psychosocial Preventative Health Model. Fifty-one percent of families presenting for survivorship care scored in the "universal" category, 34% scored in the "targeted" category, and 15% scored in the "clinical" category. Data indicate that the overall proportions of families experiencing "universal", "targeted", and "clinical" levels of familial distress may be constant from the time of diagnosis into survivorship care. Overall, the PAT2.0 demonstrated strong psychometric properties among survivors of pediatric cancer and shows promise as a psychosocial screening measure to facilitate more effective family support in survivorship care. Copyright © 2013 John Wiley & Sons, Ltd.

  2. Interaction between CYP1A2-T2467DELT polymorphism and smoking in adenocarcinoma and squamous cell carcinoma of the lung.

    PubMed

    Pavanello, Sofia; B'chir, Fatma; Pulliero, Alessandra; Saguem, Saâd; Ben Fraj, Radhia; El Aziz Hayouni, Abed; Clonfero, Erminio; Mastrangelo, Giuseppe

    2007-09-01

    This study aimed to identify new genetic characteristics contributing to individual susceptibility to smoke-induced lung cancer. Despite functional evidence of a possible role of cytochrome P450 1A2 (CYP1A2) in lung cancer susceptibility, no studies have evaluated the influence of CYP1A2 genotypes on lung cancer risk. We investigated the interaction between CYP1A2-T2467delT (allele*1D) polymorphism and smoking in Tunisian lung cancer cases (n=101 male smokers) separately for the histological types squamous cell carcinoma (SCC) (n=60) and adenocarcinoma (n=41), and in controls (n=98 male smokers) using a case-only study design. A significant interaction between CYP1A2-T/delT or delT/delT genotypes and tobacco consumption (pack-years) adjusted for age was evident (OR (95% CI) 7.78 (1.52-42.8)) in the SCC cases who smoked relatively less (< or =33 pack-years, I quartile value), but not in adenocarcinoma and controls. Our results suggest that CYP1A2-T2467delT polymorphism has an important role in lung carcinogenesis, especially SCC, among smokers.

  3. A Comparison between CHEK2*1100delC/I157T Mutation Carrier and Noncarrier Breast Cancer Patients: A Clinicopathological Analysis.

    PubMed

    Huszno, Joanna; Budryk, Magdalena; Kołosza, Zofia; Tęcza, Karolina; Pamuła Piłat, Jolanta; Nowara, Elżbieta; Grzybowska, Ewa

    2016-01-01

    The suppressor gene CHEK2 encodes a cell cycle checkpoint kinase, involved in cell cycle regulation, apoptosis and response to DNA damage. The aim of this study was to analyze the differences between CHEK2 mutation carriers (CHEK2*1100delC/I157T) and noncarriers with respect to clinicopathological factors. We reviewed the medical records of 100 early breast cancer patients (46 mutation carriers and 54 noncarriers) who were treated with chemotherapy, hormonotherapy or trastuzumab. CHEK2 mutation carriers were older (>65 years) than noncarriers (17 vs. 7%; p = 0.215). Twenty-five (54%) of them had a history of cancer in the family. Gastric cancer in the family history was detected in 11% of mutation carriers and in 2% of noncarriers (p = 0.092). There was a trend for more frequent lymph node metastases in patients without the mutation in comparison to mutation carriers (46 vs. 28%; p = 0.098). Luminal B type breast cancer was detected more often in carriers (39 vs. 20%; p = 0.048). Breast-conserving treatment was also conducted more often in mutation carriers (57 vs. 31%; p = 0.015). Histologic grades G1/G2 were detected more frequently in mutation carriers (82 vs. 70%; p = 0.212). Mutation carriers were characterized by older age, a history of gastric cancer in the family, locally advanced disease, lower histologic grade and luminal B type breast cancer. © 2016 S. Karger AG, Basel.

  4. PTGS1, PTGS2, ALOX5, ALOX12, ALOX15, and FLAP SNPs: interaction with fatty acids in colon cancer and rectal cancer.

    PubMed

    Habermann, Nina; Ulrich, Cornelia M; Lundgreen, Abbie; Makar, Karen W; Poole, Elizabeth M; Caan, Bette; Kulmacz, Richard; Whitton, John; Galbraith, Rachel; Potter, John D; Slattery, Martha L

    2013-01-01

    Dietary polyunsaturated fatty acids (PUFAs) can be converted to prostaglandins and leukotrienes. Oxygenation of omega-6 PUFAs generally results in the production of pro-inflammatory mediators, whereas oxygenated products of omega-3 (n-3) PUFAs generally have lower inflammatory activity. We hypothesize that elevated n-3 PUFA intakes from fish are associated with lower risk of colorectal cancer among those with genetic variants that result in higher levels of pro-inflammatory mediators. In population-based case-control studies of colon (case n = 1,574) and rectal cancer (case n = 791) and disease-free controls (n = 2,969), we investigated interactions between dietary fatty acid intake and 107 candidate polymorphisms and tagSNPs in PTGS1, PTGS2, ALOX12, ALOX5, ALOX15, and FLAP. The two studies used an identical genotyping protocol. We observed interactions and statistically significant increases in colon cancer risk for low docosahexaenoic acid intake among those with the PTGS1 rs10306110 (-1,053 A > G) variant genotypes (OR = 1.6, 95 % confidence interval = 1.1-2.3, adj. p = 0.06) and rectal cancer risk for low total fat intake among those with the variant PTGS1 rs10306122 (7,135 A > G) (OR(vs.wt) = 1.80, 1.02-2.99; adj. p = 0.08). The ALOX15 rs11568131 (10,339 C > T) wild type in combination with a high inflammation score (low EPA intake, high AA intake, no regular NSAID use, high BMI, smoking) was associated with increased colon cancer risk (OR = 2.28, 1.7-3.07). Rectal cancer risk was inversely associated with a low inflammation score among PTGS2 rs4648276 (3,934 T > C) variant allele carriers (OR = 0.49, 0.25-0.75). Overall, these data provide some modest evidence for interactions between dietary fat intake and genetic variation in genes involved in eicosanoid metabolism and colorectal cancer risk.

  5. N-[2-(2,2-Di-methyl-propanamido)-pyrimidin-4-yl]-2,2-di-methyl-propanamide n-hexane 0.25-solvate hemihydrate.

    PubMed

    Ośmiałowski, Borys; Valkonen, Arto; Chęcińska, Lilianna

    2013-10-05

    The asymmetric unit of the title compound, C14H22N4O2·0.25C6H14·0.5H2O, contains two independent mol-ecules of 2,4-bis-(pivaloyl-amino)-pyrimidine (M) with similar conformations, one water mol-ecule and one-half n-hexane solvent mol-ecule situated on an inversion center. In one independent M mol-ecule, one of the two tert-butyl groups is rotationally disordered between two orientations in a 3:2 ratio. The n-hexane solvent mol-ecule is disordered between two conformations in the same ratio. The water mol-ecule bridges two independent M mol-ecules via O-H⋯O, N-H⋯O and O-H⋯N hydrogen bonds into a 2M·H2O unit, and these units are further linked by N-H⋯N hydrogen bonds into chains running in the [010] direction. Weak C-H⋯O inter-actions are observed between the adjacent chains.

  6. An improved prognostic model for stage T1a and T1b prostate cancer by assessments of cancer extent

    PubMed Central

    Rajab, Ramzi; Fisher, Gabrielle; Kattan, Michael W; Foster, Christopher S; Møller, Henrik; Oliver, Tim; Reuter, Victor; Scardino, Peter T; Cuzick, Jack; Berney, Daniel M

    2013-01-01

    Treatment decisions on prostate cancer diagnosed by trans-urethral resection (TURP) of the prostate are difficult. The current TNM staging system for pT1 prostate cancer has not been re-evaluated for 25 years. Our objective was to optimise the predictive power of tumor extent measurements in TURP of the prostate specimens. A total of 914 patients diagnosed by TURP of the prostate between 1990 and 1996, managed conservatively were identified. The clinical end point was death from prostate cancer. Diagnostic serum prostate-specific antigen (PSA) and contemporary Gleason grading was available. Cancer extent was measured by the percentage of chips infiltrated by cancer. Death rates were compared by univariate and multivariate proportional hazards models, including baseline PSA and Gleason score. The percentage of positive chips was highly predictive of prostate cancer death when assessed as a continuous variable or as a grouped variable on the basis of and including the quintiles, quartiles, tertiles and median groups. In the univariate model, the most informative variable was a four group-split (≤ 10%, >10–25%, > 25–75% and > 75%); (HR = 2.08, 95% CI = 1.8–2.4, P < 0.0001). The same was true in a multivariate model (ΔX2 (1 d.f.) = 15.0, P = 0.0001). The current cutoff used by TNM (< = 5%) was sub-optimal (ΔX2 (1 d.f.) = 4.8, P = 0.023). The current TNM staging results in substantial loss of information. Staging by a four-group subdivision would substantially improve prognostication in patients with early stage disease and also may help to refine management decisions in patients who would do well with conservative treatments. PMID:20834240

  7. Synthesis and X-ray structures of dilithium complexes of the phosphonate anions [PhP(E)(N(t)Bu)(2)](2-) (E = O, S, Se, Te) and dimethylaluminum derivatives of [PhP(E)(N(t)Bu)(NH(t)Bu)](-) (E = S, Se).

    PubMed

    Briand, Glen G; Chivers, Tristram; Krahn, Mark; Parvez, Masood

    2002-12-16

    The dilithium salts of the phosphonate dianions [PhP(E)(N(t)Bu)(2)](2-) (E = O, S, Se) are generated by the lithiation of [PhP(E)(NH(t)Bu)(2)] with n-butyllithium. The formation of the corresponding telluride (E = Te) is achieved by oxidation of [Li(2)[PhP(N(t)Bu)(2)

  8. Anaylyzing powers for the reaction π-p-->-->π0n at T-π=161 MeV

    NASA Astrophysics Data System (ADS)

    Görgen, J. J.; Comfort, J. R.; Averett, T.; Dekorse, J.; Franklin, B.; Ritchie, B. G.; Tinsley, J.; Kyle, G.; Berman, B.; Burleson, G.; Cranston, K.; Klein, A.; Faucett, J. A.; Jarmer, J. J.; Knudson, J. N.; Penttilä, S.; Tanaka, N.; Brinkmöller, B.; Dehnhard, D.; Yen, Y. F.; Høibrråten, S.; Breuer, H.; Flanders, B. S.; Khandaker, M. A.; Naples, D. L.; Zhang, D.; Barlett, M. L.; Hoffmann, G. W.; Purcell, M.

    1990-10-01

    Analyzing powers for the reaction π-p-->-->π0n were measured at an incident pion energy of T-π=161 MeV with a transversely polarized proton target over the angular range of about 20°-60°. The results are well described by calculations based on current sets of πN phase shifts.

  9. Simultaneous Measurement of T2 and Apparent Diffusion Coefficient (T2+ADC) in the Heart With Motion-Compensated Spin Echo Diffusion-Weighted Imaging

    PubMed Central

    Aliotta, Eric; Moulin, Kévin; Zhang, Zhaohuan; Ennis, Daniel B.

    2018-01-01

    Purpose To evaluate a technique for simultaneous quantitative T2 and apparent diffusion coefficient (ADC) mapping in the heart (T2+ADC) using spin echo (SE) diffusion-weighted imaging (DWI). Theory and Methods T2 maps from T2+ADC were compared with single-echo SE in phantoms and with T2-prepared (T2-prep) balanced steady-state free precession (bSSFP) in healthy volunteers. ADC maps from T2+ADC were compared with conventional DWI in phantoms and in vivo. T2+ADC was also demonstrated in a patient with acute myocardial infarction (MI). Results Phantom T2 values from T2+ADC were closer to a single-echo SE reference than T2-prep bSSFP (−2.3 ± 6.0% vs 22.2 ± 16.3%; P < 0.01), and ADC values were in excellent agreement with DWI (0.28 ± 0.4%). In volunteers, myocardial T2 values from T2+ADC were significantly shorter than T2-prep bSSFP (35.8 ± 3.1 vs 46.8 ± 3.8 ms; P < 0.01); myocardial ADC was not significantly (N.S.) different between T2+ADC and conventional motion-compensated DWI (1.39 ± 0.18 vs 1.38 ± 0.18 mm2/ms; P = N.S.). In the patient, T2 and ADC were both significantly elevated in the infarct compared with remote myocardium (T2: 40.4 ± 7.6 vs 56.8 ± 22.0; P < 0.01; ADC: 1.47 ± 0.59 vs 1.65 ± 0.65 mm2/ms; P < 0.01). Conclusion T2+ADC generated coregistered, free-breathing T2 and ADC maps in healthy volunteers and a patient with acute MI with no cost in accuracy, precision, or scan time compared with DWI. PMID:28516485

  10. Interface properties of an O2 annealed Au/Ni/n-Al0.18Ga0.82N Schottky contact

    NASA Astrophysics Data System (ADS)

    Legodi, M. J.; Meyer, W. E.; Auret, F. D.

    2012-05-01

    We oxidized a Ni/Au metal bi-layer contact fabricated on HVPE Al0.18Ga0.82N from 373 K to 573 K in 100 K steps. In the range 1 kHz to 2 MHz, the Capacitance-Voltage-Frequency (C-V-f) measurements reveal a frequency dispersion of the capacitance and the presence of an anomalous peak at 0.4 V owing to the presence of interface states in the as deposited contact system. The dispersion was progressively removed by O2 anneals from temperatures as low as 373 K. These changes are accompanied by an improvement in the overall quality of the Schottky system: the ideality factor, n, improves from 2.09 to 1.26; the Schottky barrier height (SBH), determined by the Norde [1] method, increases from 0.72 eV to 1.54 eV. From the Nicollian and Goetzberger model [2], we calculated the energy distribution of the density of interface states, NSS. Around 1 eV above the Al0.18Ga0.82N valence band, NSS, decreases from 2.3×1012 eV-1 cm-2 for the un-annealed diodes to 1.3×1012 eV-1 cm-2 after the 573 K anneal. Our results suggest the formation of an insulating NiO leading to a MIS structure for the oxidized Au/Ni/Al0.18Ga0.82N contact.

  11. Photodynamic therapy (PDT) with endoscopic ultrasound for the treatment of esophageal cancer

    NASA Astrophysics Data System (ADS)

    Woodward, Timothy A.; Wolfsen, Herbert C.

    2000-05-01

    In 1995, PDT was approved for palliative use in patients with esophageal cancer. We report our experience using PDT to treat esophageal cancer patients previously treated with combination chemotherapy and radiation therapy. In our series, nine patients referred for PDT with persistent esophageal cancer after chemo-radiation therapy. We found: (1) All patients were men with a mean age of 63 years and eight out of nine had adenocarcinoma with Barrett's esophagus; (2) All patients required endoscopic dilation after PDT; (3) At a mean follow up of 4 months, two T2N0 patients had no demonstrable tumor and all three T3N0 patients had greater than 50% tumor reduction (the partially responsive T3N0 patients will be offered repeat PDT); (4) Patients with metastatic disease (T3N1 or M1) had effective dysphagia palliation. Thus, PDT is safe and effective in ablating all or most tumor in patients with persistent esophageal cancer after chemotherapy and radiation therapy.

  12. Melanoma staging: Evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual.

    PubMed

    Gershenwald, Jeffrey E; Scolyer, Richard A; Hess, Kenneth R; Sondak, Vernon K; Long, Georgina V; Ross, Merrick I; Lazar, Alexander J; Faries, Mark B; Kirkwood, John M; McArthur, Grant A; Haydu, Lauren E; Eggermont, Alexander M M; Flaherty, Keith T; Balch, Charles M; Thompson, John F

    2017-11-01

    Answer questions and earn CME/CNE To update the melanoma staging system of the American Joint Committee on Cancer (AJCC) a large database was assembled comprising >46,000 patients from 10 centers worldwide with stages I, II, and III melanoma diagnosed since 1998. Based on analyses of this new database, the existing seventh edition AJCC stage IV database, and contemporary clinical trial data, the AJCC Melanoma Expert Panel introduced several important changes to the Tumor, Nodes, Metastasis (TNM) classification and stage grouping criteria. Key changes in the eighth edition AJCC Cancer Staging Manual include: 1) tumor thickness measurements to be recorded to the nearest 0.1 mm, not 0.01 mm; 2) definitions of T1a and T1b are revised (T1a, <0.8 mm without ulceration; T1b, 0.8-1.0 mm with or without ulceration or <0.8 mm with ulceration), with mitotic rate no longer a T category criterion; 3) pathological (but not clinical) stage IA is revised to include T1b N0 M0 (formerly pathologic stage IB); 4) the N category descriptors "microscopic" and "macroscopic" for regional node metastasis are redefined as "clinically occult" and "clinically apparent"; 5) prognostic stage III groupings are based on N category criteria and T category criteria (ie, primary tumor thickness and ulceration) and increased from 3 to 4 subgroups (stages IIIA-IIID); 6) definitions of N subcategories are revised, with the presence of microsatellites, satellites, or in-transit metastases now categorized as N1c, N2c, or N3c based on the number of tumor-involved regional lymph nodes, if any; 7) descriptors are added to each M1 subcategory designation for lactate dehydrogenase (LDH) level (LDH elevation no longer upstages to M1c); and 8) a new M1d designation is added for central nervous system metastases. This evidence-based revision of the AJCC melanoma staging system will guide patient treatment, provide better prognostic estimates, and refine stratification of patients entering clinical trials. CA

  13. Utility of dysphagia grade in predicting endoscopic ultrasound T-stage of non-metastatic esophageal cancer.

    PubMed

    Fang, T C; Oh, Y S; Szabo, A; Khan, A; Dua, K S

    2016-08-01

    Patients with non-metastatic esophageal cancer routinely undergo endoscopic ultrasound (EUS) for loco-regional staging. Neoadjuvant therapy is recommended for ≥T3 tumors while upfront surgery can be considered for ≤T2 lesions. The aim of this study was to determine if the degree of dysphagia can predict the EUS T-stage of esophageal cancer. One hundred eleven consecutive patients with non-metastatic esophageal cancer were retrospectively reviewed from a database. Prior to EUS, patients' dysphagia grade was recorded. Correlation between dysphagia grade and EUS T-stage, especially in reference to predicting ≥T3 stage, was determined. The correlation of dysphagia grade with EUS T-stage (Kendall's tau coefficient) was 0.49 (P < 0.001) for the lower and 0.59 (P = 0.008) for the middle esophagus. The sensitivity and specificity of dysphagia grade ≥2 (can only swallow semi-solids/liquids) for T3 cancer were 56% (95% confidence interval [CI] 43-67%) and 93% (95% CI 79-98%), respectively. The sensitivity, specificity, and positive predictive value of dysphagia grade ≥3 (can only swallow liquids or total dysphagia) for T3 lesions were 36% (95% CI 25-48%), 100% (95% CI 89-100%), and 100% (95% CI 83-100%), respectively. Overall, there was a significant positive correlation between dysphagia grade and the EUS T-stage of esophageal cancer. All patients with dysphagia grade ≥3 had T3 lesions. This may have clinical implications for patients who can only swallow liquids or have complete dysphagia by allowing for prompt initiation of neoadjuvant therapy, especially in countries/centers where EUS service is difficult to access in a timely manner or not available. © 2015 International Society for Diseases of the Esophagus.

  14. Effects of La0.2Ce0.6Eu0.2F3 nanocrystals capped with polyethylene glycol on human pancreatic cancer cells in vitro

    NASA Astrophysics Data System (ADS)

    Withers, Nathan J.; Glazener, Natasha N.; Rivera, Antonio C.; Akins, Brian A.; Armijo, Leisha M.; Plumley, John B.; Cook, Nathaniel C.; Sugar, Jacqueline M.; Chan, Rana; Brandt, Yekaterina I.; Smolyakov, Gennady A.; Heintz, Philip H.; Osiński, Marek

    2013-02-01

    Lanthanide fluoride colloidal nanocrystals offer a way to improve the diagnosis and treatment of cancer through the enhanced absorption of ionizing radiation, in addition to providing visible luminescence. In order to explore this possibility, tests with a kilovoltage therapy unit manufactured by the Universal X-Ray Company were performed to estimate the energy sensitivity of this technique. La0.2Ce0.6Eu0.2F3 nanocrystals capped with polyethylene glycol of molecular weight 6000 were synthesized, suspended in deionized water, and made tolerant to biological ionic pressures by incubation with fetal bovine serum. These nanocrystals were characterized by dynamic light scattering, muffle furnace ashing, and photoluminescence spectroscopy. Clonogenic assays were performed on the cells to assay the cytotoxicity and radiotoxicity of the nanocrystals on the human pancreatic cancer cell line PANC-1, purchased from ATCC.

  15. Increased therapeutic ratio by 18FDG-PET CT planning in patients with clinical CT stage N2-N3M0 non-small-cell lung cancer: a modeling study.

    PubMed

    van Der Wel, Antoinet; Nijsten, Sebastiaan; Hochstenbag, Monique; Lamers, Rob; Boersma, Liesbeth; Wanders, Rinus; Lutgens, Ludy; Zimny, Michael; Bentzen, Søren M; Wouters, Brad; Lambin, Philippe; De Ruysscher, Dirk

    2005-03-01

    With this modeling study, we wanted to estimate the potential gain from incorporating fluorodeoxyglucose-positron emission tomography (FDG-PET) scanning in the radiotherapy treatment planning of CT Stage N2-N3M0 non-small-cell lung cancer (NSCLC) patients. Twenty-one consecutive patients with clinical CT Stage N2-N3M0 NSCLC were studied. For each patient, two three-dimensional conformal treatment plans were made: one with a CT-based planning target volume (PTV) and one with a PET-CT-based PTV, both to deliver 60 Gy in 30 fractions. From the dose-volume histograms and dose distributions on each plan, the dosimetric factors predicting esophageal and lung toxicity were analyzed and compared. For each patient, the maximal tolerable prescribed radiation dose for the CT PTV vs. PET-CT PTV was calculated according to the constraints for the lung, esophagus, and spinal cord. From these results, the tumor control probability (TCP) was estimated, assuming a clinical dose-response curve with a median toxic dose of 84.5 Gy and a gamma(50) of 2.0. Dose-response curves were modeled, taking into account geographic misses according to the accuracy of CT and PET in our institutions. The gross tumor volume of the nodes decreased from 13.7 +/- 3.8 cm(3) on the CT scan to 9.9 +/- 4.0 cm(3) on the PET-CT scan (p = 0.011). All dose-volume characteristics for the esophagus and lungs decreased in favor of PET-CT. The esophageal V(45) (the volume of the esophagus receiving 45 Gy) decreased from 45.2% +/- 4.9% to 34.0% +/- 5.8% (p = 0.003), esophageal V(55) (the volume of the esophagus receiving 55 Gy) from 30.6% +/- 3.2% to 21.9% +/- 3.8% (p = 0.004), mean esophageal dose from 29.8 +/- 2.5 Gy to 23.7 +/- 3.1 Gy (p = 0.004), lung V(20) (the volume of the lungs minus the PTV receiving 20 Gy) from 24.9% +/- 2.3% to 22.3% +/- 2.2% (p = 0.012), and mean lung dose from 14.7 +/- 1.3 Gy to 13.6 +/- 1.3 Gy (p = 0.004). For the same toxicity levels of the lung, esophagus, and spinal cord, the dose

  16. Predicting the nodal status in gastric cancers: The role of apparent diffusion coefficient histogram characteristic analysis.

    PubMed

    Liu, Song; Zhang, Yujuan; Xia, Jie; Chen, Ling; Guan, Wenxian; Guan, Yue; Ge, Yun; He, Jian; Zhou, Zhengyang

    2017-10-01

    To explore the application of histogram analysis in preoperative T and N staging of gastric cancers, with a focus on characteristic parameters of apparent diffusion coefficient (ADC) maps. Eighty-seven patients with gastric cancers underwent diffusion weighted magnetic resonance imaging (b=0, 1000s/mm 2 ), which generated ADC maps. Whole-volume histogram analysis was performed on ADC maps and 7 characteristic parameters were obtained. All those patients underwent surgery and postoperative pathologic T and N stages were determined. Four parameters, including skew, kurtosis, s-sD av and sample number, showed significant differences among gastric cancers at different T and N stages. Most parameters correlated with T and N stages significantly and worked in differentiating gastric cancers at different T or N stages. Especially skew yielded a sensitivity of 0.758, a specificity of 0.810, and an area under the curve (AUC) of 0.802 for differentiating gastric cancers with and without lymph node metastasis (P<0.001). All the parameters, except AUC low , showed good or excellent inter-observer agreement with intra-class correlation coefficients ranging from 0.710 to 0.991. Characteristic parameters derived from whole-volume ADC histogram analysis could help assessing preoperative T and N stages of gastric cancers. Copyright © 2017. Published by Elsevier Inc.

  17. Association Studies of Fcγ Receptor Polymorphisms with Outcome in HER2+ Breast Cancer Patients Treated with Trastuzumab in NCCTG (Alliance) Trial N9831

    PubMed Central

    Norton, Nadine; Olson, Rebecca M.; Pegram, Mark; Tenner, Kathleen; Ballman, Karla V.; Clynes, Raphael; Knutson, Keith L.; Perez, Edith A.

    2014-01-01

    Patients with HER2+ breast cancer treated with trastuzumab and chemotherapy have superior survival compared to patients treated with chemotherapy alone. Polymorphisms within FCGR2A and FCGR3A are associated with binding affinity of natural killer cells to the IgG1 portion of trastuzumab and a polymorphism in FCGR2B (I232T) is associated with impaired regulatory activity. The association of these polymorphisms with clinical response among trastuzumab-treated patients is equivocal with both positive and negative associations. We performed genotyping analysis on the FCGR3A V158F, FCGR2A R131H, and FCGR2B I232T genes in 1,325 patients from the N9831 clinical trial. Patients in Arm A (N=419) received chemotherapy only. Patients in Arms B (N=469) and C (N=437) were treated with chemotherapy and trastuzumab, (sequentially in Arm B and concurrently in Arm C). Using log-rank test and Cox proportional hazard models, we compared disease-free survival (DFS) among genotypic groups within pooled Arms B/C. We found no differences in DFS between trastuzumab-treated patients who had the FCGR3A 158 V/V and/or FCGR2A 131 H/H high affinity genotypes and patients without those genotypes. Furthermore, there was no significant interaction between FCGR3A and FCGR2A and treatment. However, there was a difference in DFS for FCGR2B I232T with I/I patients deriving benefit from trastuzumab (p<0.001) compared to the T carriers who did not (p=0.81). The interaction between FCGR2B genotype and treatment was statistically significant (p=0.03). Our analysis did not reveal an association between FcγR high affinity genotypes and outcomes. However, it appears that the FCGR2B inhibitory gene may be predictive of adjuvant trastuzumab benefit. PMID:24989892

  18. Synthesis and evaluation of the NSCLC anti-cancer activity and physical properties of 4-aryl-N-phenylpyrimidin-2-amines.

    PubMed

    Toviwek, Borvornwat; Suphakun, Praphasri; Choowongkomon, Kiattawee; Hannongbua, Supa; Gleeson, M Paul

    2017-10-15

    Reported herein are efforts to profile 4-aryl-N-phenylpyrimidin-2-amines in terms of their anti-cancer activity towards non small-cell lung carcinoma (NSCLC) cells. We have synthesized new 4-aryl-N-phenylpyrimidin-2-amines and assessed them in terms of their cytotoxicity (A549, NCI-H187, MCF7, Vero & KB) and physicochemical properties (logD 7.4 and solubility). 13f and 13c demonstrated potent anti-cancer activity in A549 cells (0.2µM), compared to 0.4μM for the NSCLC drug Doxorubicin. 13f also displayed low experimental logD 7.4 (2.9) and the best solubility (∼40μM). Compounds 13b and 13d showed the best balance of A549 anti-cancer activity and selectivity. 13g showed good activity and selectivity comparable with the anti-cancer drug Doxorubicin. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Pressure-induced shift of T c and structural transition in “122” type pnictide superconductor Ca 0.34Na 0.66Fe 2As 2

    DOE PAGES

    Zhang, Sijia; Zhao, Kan; Yu, Xiaohui; ...

    2016-07-11

    Here, the effect of pressure on superconductivity of “122” type Ca 1-xNa xFe 2As 2 (x=0.66 single crystal is investigated through the temperature dependence of resistanc measurement. Optimal Na doped (Ca 0.34Na 0.66)Fe 2As 2 shows a superconductin transition with T c ~ 33 K at ambient pressure. With application of pressure, T decreases nearly linearly with d Tc/d P ~ -1.7K/GPa at pressures lower than 2 GPa and disappears gradually at higher pressure. The disappearance of superconductivit is also companied with the recovery of standard Fermi liquid behaviors of th normal-state transport properties. Moreover, (Ca 0.34Na 0.66)Fe 2As 2more » exhibits a tetragona (T) to collapsed-tetragonal (c T) transition at about 3 GPa. The evolution o non-Fermi liquid behaviors and superconductivity under pressure are both relate to the interband fluctuations.« less

  20. ECO2N V. 2.0: A New TOUGH2 Fluid Property Module for Mixtures of Water, NaCl, and CO 2

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Pan, L.; Spycher, N.; Doughty, C.

    2014-12-01

    ECO2N V2.0 is a fluid property module for the TOUGH2 simulator (Version 2.1) that was designed for applications to geologic sequestration of CO 2 in saline aquifers and enhanced geothermal reservoirs. ECO2N V2.0 is an enhanced version of the previous ECO2N V1.0 module (Pruess, 2005). It expands the temperature range up to about 300°C whereas V1.0 can only be used for temperatures below about 110°C. V2.0 includes a comprehensive description of the thermodynamics and thermophysical properties of H 2O - NaCl -CO 2 mixtures, that reproduces fluid properties largely within experimental error for the temperature, pressure and salinity conditions ofmore » interest (10 °C < T < 300 °C; P < 600 bar; salinity up to halite saturation). This includes density, viscosity, and specific enthalpy of fluid phases as functions of temperature, pressure, and composition, as well as partitioning of mass components H 2O, NaCl and CO 2 among the different phases. In particular, V2.0 accounts for the effects of water on the thermophysical properties of the CO 2-rich phase, which was ignored in V1.0, using a model consistent with the solubility models developed by Spycher and Pruess (2005, 2010). In terms of solubility models, V2.0 uses the same model for partitioning of mass components among the different phases (Spycher and Pruess, 2005) as V1.0 for the low temperature range (<99°C) but uses a new model (Spycher and Pruess, 2010) for the high temperature range (>109°C). In the transition range (99-109°C), a smooth interpolation is applied to estimate the partitioning as a function of the temperature. Flow processes can be modeled isothermally or non-isothermally, and phase conditions represented may include a single (aqueous or CO 2-rich) phase, as well as two-phase mixtures. Fluid phases may appear or disappear in the course of a simulation, and solid salt may precipitate or dissolve. This report gives technical specifications of ECO2N V2.0 and includes instructions for

  1. [Effects of concurrent S-1, nedaplatin/radiation therapy for 5 cases of head and neck cancer with esophageal carcinoma].

    PubMed

    Shimane, Toshikazu; Mori, Tomoaki; Ono, Tomohiro; Egawa, Shunya; Furuya, Ayako; Kobayashi, Sei; Sanbe, Takeyuki; Suzaki, Harumi

    2010-07-01

    It is not rare to observe multiple cancers in cases of head and neck carcinoma. Such cancers are important factors for deciding the therapeutic strategy. Complications of esophageal cancer are particularly frequent in cases of hypopharyngeal cancer in comparison to other head and neck tumors. At our department, for organ and functional preservation, and radical cure, we have used simultaneous therapy instead of separate therapy for head and neck tumors and esophageal cancer. We have been implementing concurrent S-1, nedaplatin/radiation therapy (hereinafter called SN therapy) for cases of advanced cancer of the head and neck, and we applied the same therapy for cases of head and neck carcinoma with esophageal cancer. The subjects comprised 5 cases of head and neck tumors complicated by esophageal cancer for which therapy was conducted at our department between April 2005 and March 2009. The histologic type was squamous cell carcinoma in all of the cases. There were 2 cases of laryngeal cancer (T3N2cM0, T3N0M0) and 3 cases of hypopharyngeal cancer (T3N2cM0, T4N2cM0, T3N2bM0). As a result, 3 out of the 5 cases have remained cancer-free, and the average observation period was 29. 3 months. One case expired due to an unrelated cause as a result of cardiac disease, while in the remaining case, the tumor did not disappear and the patient died due to the disease. It is necessary to continue examining the survival rate by increasing the number of cases.

  2. Recommendations for clinical staging (cTNM) of cancer of the esophagus and esophagogastric junction for the 8th edition AJCC/UICC staging manuals.

    PubMed

    Rice, Thomas W; Ishwaran, Hemant; Blackstone, Eugene H; Hofstetter, Wayne L; Kelsen, David P; Apperson-Hansen, Carolyn

    2016-11-01

    We report analytic and consensus processes that produced recommendations for clinical stage groups (cTNM) of esophageal and esophagogastric junction cancer for the AJCC/UICC cancer staging manuals, 8th edition. The Worldwide Esophageal Cancer Collaboration (WECC) provided data on 22,123 clinically staged patients with epithelial esophageal cancers. Risk-adjusted survival for each patient was developed using random survival forest analysis from which (1) data-driven clinical stage groups were identified wherein survival decreased monotonically and was distinctive between and homogeneous within groups and (2) data-driven anatomic clinical stage groups based only on cTNM. The AJCC Upper GI Task Force, by smoothing, simplifying, expanding, and assessing clinical applicability, produced (3) consensus clinical stage groups. Compared with pTNM, cTNM survival was "pinched," with poorer survival for early cStage groups and better survival for advanced ones. Histologic grade was distinctive for data-driven grouping of cT2N0M0 squamous cell carcinoma (SCC) and cT1-2N0M0 adenocarcinoma, but consensus removed it. Grouping was different by histopathologic cell type. For SCC, cN0-1 was distinctive for cT3 but not cT1-2, and consensus removed cT4 subclassification and added subgroups 0, IVA, and IVB. For adenocarcinoma, N0-1 was distinctive for cT1-2 but not cT3-4a, cStage II subgrouping was necessary (T1N1M0 [IIA] and T2N0M0 [IIB]), advanced cancers cT3-4aN0-1M0 plus cT2N1M0 comprised cStage III, and consensus added subgroups 0, IVA, and IVB. Treatment decisions require accurate cStage, which differs from pStage. Understaging and overstaging are problematic, and additional factors, such as grade, may facilitate treatment decisions and prognostication until clinical staging techniques are uniformly applied and improved. © 2016 International Society for Diseases of the Esophagus.

  3. Recommendations for clinical staging (cTNM) of cancer of the esophagus and esophagogastric junction for the 8th edition AJCC/UICC staging manuals

    PubMed Central

    Rice, Thomas W.; Ishwaran, Hemant; Blackstone, Eugene H.; Hofstetter, Wayne L.; Kelsen, David P.; Apperson-Hansen, Carolyn

    2017-01-01

    SUMMARY We report analytic and consensus processes that produced recommendations for clinical stage groups (cTNM) of esophageal and esophagogastric junction cancer for the AJCC/UICC cancer staging manuals, 8th edition. The Worldwide Esophageal Cancer Collaboration (WECC) provided data on 22,123 clinically staged patients with epithelial esophageal cancers. Risk-adjusted survival for each patient was developed using random survival forest analysis from which (1) data-driven clinical stage groups were identified wherein survival decreased monotonically and was distinctive between and homogeneous within groups and (2) data-driven anatomic clinical stage groups based only on cTNM. The AJCC Upper GI Task Force, by smoothing, simplifying, expanding, and assessing clinical applicability, produced (3) consensus clinical stage groups. Compared with pTNM, cTNM survival was “pinched,” with poorer survival for early cStage groups and better survival for advanced ones. Histologic grade was distinctive for data-driven grouping of cT2N0M0 squamous cell carcinoma (SCC) and cT1-2N0M0 adenocarcinoma, but consensus removed it. Grouping was different by histopathologic cell type. For SCC, cN0-1 was distinctive for cT3 but not cT1-2, and consensus removed cT4 subclassification and added subgroups 0, IVA, and IVB. For adenocarcinoma, N0-1 was distinctive for cT1-2 but not cT3-4a, cStage II subgrouping was necessary (T1N1M0 [IIA] and T2N0M0 [IIB]), advanced cancers cT3-4aN0-1M0 plus cT2N1M0 comprised cStage III, and consensus added subgroups 0, IVA, and IVB. Treatment decisions require accurate cStage, which differs from pStage. Understaging and overstaging are problematic, and additional factors, such as grade, may facilitate treatment decisions and prognostication until clinical staging techniques are uniformly applied and improved. PMID:27905171

  4. Obesity and Prostate Cancer Risk According to Tumor TMPRSS2:ERG Gene Fusion Status

    PubMed Central

    Egbers, Lieke; Luedeke, Manuel; Rinckleb, Antje; Kolb, Suzanne; Wright, Jonathan L.; Maier, Christiane; Neuhouser, Marian L.; Stanford, Janet L.

    2015-01-01

    The T2E gene fusion, formed by fusion of the transmembrane protease, serine 2, gene (TMPRSS2) with the erythroblast transformation-specific (ETS)-related gene (ERG), is found in approximately 50% of prostate cancers and may characterize distinct molecular subtypes of prostate cancer with different etiologies. We investigated the relationship between body mass index (BMI; weight (kg)/height (m)2) and prostate cancer risk by T2E status. Study participants were residents of King County, Washington, recruited for 2 population-based case-control studies conducted in 1993–1996 and 2002–2005. Tumor T2E status was determined for 563 prostate cancer patients who underwent radical prostatectomy. Information on weight, height, and covariables was obtained through in-person interviews. We performed polytomous logistic regression to calculate odds ratios and 95% confidence intervals for T2E-positive and -negative prostate cancer. Comparing the highest BMI quartile with the lowest, inverse associations were observed between recent (≥29.7 vs. <24.5: odds ratio = 0.66, 95% confidence interval: 0.45, 0.97) and maximum (≥31.8 vs. <25.9: odds ratio = 0.69, 95% confidence interval: 0.47, 1.02) BMI and the risk of T2E-positive prostate cancer. No significant associations were seen for men with T2E-negative tumors. This study provides evidence that obesity is specifically associated with reduced risk of developing androgen-responsive T2E fusion–positive tumors. The altered steroid hormone profile in obese men may contribute to this inverse association. PMID:25852077

  5. Survival outcomes with concurrent chemoradiation for elderly patients with locally advanced head and neck cancer according to the National Cancer Data Base.

    PubMed

    Amini, Arya; Jones, Bernard L; McDermott, Jessica D; Serracino, Hilary S; Jimeno, Antonio; Raben, David; Ghosh, Debashis; Bowles, Daniel W; Karam, Sana D

    2016-05-15

    The overall survival (OS) benefit of concurrent chemoradiotherapy (CRT) for head and neck squamous cell carcinoma patients older than 70 years is debated. This study examines the outcomes of elderly patients receiving CRT versus radiotherapy (RT) alone. The National Cancer Data Base was queried for patients older than 70 years with nonmetastatic oropharyngeal, laryngeal, or hypopharyngeal cancer (T3-4 or N(+)). CRT was defined as chemotherapy started within 14 days of the initiation of RT. Univariate analysis, multivariate analysis (MVA), propensity score matching (PSM), and recursive partitioning analysis (RPA) were performed. The study included 4042 patients: 2538 (63%) received CRT. The median follow-up was 19 months. The unadjusted median OS was longer with the addition of CRT (P < .001). OS was superior with CRT in the MVA (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.58-0.68; P < .001) and PSM analyses (HR, 0.73; 95% CI, 0.66-0.80; P < .001) in comparison with RT alone. According to RPA, CRT was associated with longer OS for patients 81 years or younger with low comorbidity scores and either T1-2/N2-3 disease or T3-4/N0-3 disease. The survival benefit with CRT disappeared for 2 subgroups in the 71- to 81-year age range: those with T1-2, N1, and Charlson-Deyo 0-1 (CD0-1) disease and those with T3-4, N1+, and CD1+ disease. Patients who were older than 81 years did not have increased survival with CRT. The receipt of CRT was associated with a longer duration of RT (odds ratio, 1.74; 95% CI, 1.50-2.01; P < .001). Patients older than 70 years should not be denied concurrent chemotherapy solely on the basis of age; additional factors, including the performance status and the tumor stage, should be taken into account. Cancer 2016;122:1533-43. © 2016 American Cancer Society. © 2016 American Cancer Society.

  6. Symptom overlap between laryngopharyngeal reflux and glottic insufficiency in vocal fold atrophy patients.

    PubMed

    Patel, Anju K; Mildenhall, Nicholas R; Kim, William; Carroll, Thomas L

    2014-04-01

    To determine in true vocal fold (TVF) atrophy patients if symptoms of throat clearing and mucus sensation, attributed to laryngopharyngeal reflux (LPR), are due to glottic insufficiency. Is the TVF atrophy population being prescribed proton pump inhibitors unnecessarily? A retrospective review of patients with TVF atrophy but no other underlying laryngeal pathology seen at a tertiary voice center from July 2009 to May 2012 was conducted. Patient demographics, symptoms, LPR diagnosis, interventions, and pre-intervention and post-intervention Voice Handicap Index-10 (VHI) and Reflux Symptom Index (RSI) scores were recorded. Twenty-six patients met inclusion criteria, and 85% were treated for LPR. Throat clearing and mucus sensation (85%), dysphonia (54%), and globus sensation (46%) were recorded. Interventions included LPR medical management (65%), vocal fold augmentation (23%), and voice therapy (12%). Reflux Symptom Index scores improved in all groups. Voice Handicap Index-10 and RSI scores normalized in patients treated with augmentation. Globus was never present in patients who received augmentation. Throat clearing and mucus sensation may be due to underlying glottic insufficiency and changes of the aging larynx rather than LPR. High VHI and RSI scores normalized with TVF augmentation. Further work is needed to evaluate symptom presentation and risk versus benefit of treatment options, especially if it avoids unnecessary proton pump inhibitor trials.

  7. CHEK2 mutations and the risk of papillary thyroid cancer.

    PubMed

    Siołek, Monika; Cybulski, Cezary; Gąsior-Perczak, Danuta; Kowalik, Artur; Kozak-Klonowska, Beata; Kowalska, Aldona; Chłopek, Małgorzata; Kluźniak, Wojciech; Wokołorczyk, Dominika; Pałyga, Iwona; Walczyk, Agnieszka; Lizis-Kolus, Katarzyna; Sun, Ping; Lubiński, Jan; Narod, Steven A; Góźdż, Stanisław

    2015-08-01

    Mutations in the cell cycle checkpoint kinase 2 (CHEK2) tumor suppressor gene are associated with multi-organ cancer susceptibility including cancers of the breast and prostate. A genetic association between thyroid and breast cancer has been suggested, however little is known about the determinants of this association. To characterize the association of CHEK2 mutations with thyroid cancer, we genotyped 468 unselected patients with papillary thyroid cancer and 468 (matched) cancer-free controls for four founder mutations of CHEK2 (1100delC, IVS2 + 1G>A, del5395 and I157T). We compared the family histories reported by patients with a CHEK2 mutation to those of non-carriers. A CHEK2 mutation was seen in 73 of 468 (15.6%) unselected patients with papillary thyroid cancer, compared to 28 of 460 (6.0%) age- and sex-matched controls (OR 3.3; p < 0.0001). A truncating mutation (IVS2 + 1G>A, 1100delC or del5395) was associated with a higher risk of thyroid cancer (OR = 5.7; p = 0.006), than was the missense mutation I157T (OR = 2.8; p = 0.0001). CHEK2 mutation carriers reported a family history of breast cancer 2.2 times more commonly than non-carriers (16.4% vs.8.1%; p = 0.05). A CHEK2 mutation was found in seven of 11 women (63%) with multiple primary cancers of the breast and thyroid (OR = 10; p = 0.0004). These results suggest that CHEK2 mutations predispose to thyroid cancer, familial aggregations of breast and thyroid cancer and to double primary cancers of the breast and thyroid. © 2015 UICC.

  8. NDEx 2.0: A Clearinghouse for Research on Cancer Pathways.

    PubMed

    Pratt, Dexter; Chen, Jing; Pillich, Rudolf; Rynkov, Vladimir; Gary, Aaron; Demchak, Barry; Ideker, Trey

    2017-11-01

    We present NDEx 2.0, the latest release of the Network Data Exchange (NDEx) online data commons (www.ndexbio.org) and the ways in which it can be used to (i) improve the quality and abundance of biological networks relevant to the cancer research community; (ii) provide a medium for collaboration involving networks; and (iii) facilitate the review and dissemination of networks. We describe innovations addressing the challenges of an online data commons: scalability, data integration, data standardization, control of content and format by authors, and decentralized mechanisms for review. The practical use of NDEx is presented in the context of a novel strategy to foster network-oriented communities of interest in cancer research by adapting methods from academic publishing and social media. Cancer Res; 77(21); e58-61. ©2017 AACR . ©2017 American Association for Cancer Research.

  9. Neoadjuvant Systemic Therapy Use for Younger Patients with Breast Cancer Treated in Different Types of Cancer Centers Across the United States.

    PubMed

    Mohiuddin, Jahan J; Deal, Allison M; Carey, Lisa A; Lund, Jennifer L; Baker, Brock R; Zagar, Timothy M; Jones, Ellen L; Marks, Lawrence B; Chen, Ronald C

    2016-11-01

    Multiple clinical trials have shown that neoadjuvant systemic therapy has a benefit in women who are borderline lumpectomy candidates and in those with locally advanced breast cancers by reducing the mastectomy rate and making inoperable tumors operable. The study aim was to examine the patterns of neoadjuvant chemotherapy and endocrine therapy use among younger women in the United States treated at different types of cancer centers. Data from the National Cancer Data Base for 118,086 women younger than 65 years with clinical stage IIA (T2N0 only) to IIIC breast cancer. Following the National Comprehensive Cancer Network guideline categorization, patients were grouped into those who were borderline lumpectomy candidates (clinical stage IIA [T2N0 only], IIB, or IIIA [T3N1 only]) or those with locally advanced disease (clinical stage IIIA [T0-3N2 only], IIIB, or IIIC). The main outcome was the proportion of women who received neoadjuvant systemic therapy. Use of neoadjuvant chemotherapy ranged from 17% (stage IIA) to 79% (stage IIIB). Across almost all stage and receptor subtypes, the use was lower in community vs academic centers. On multivariable analysis, use of neoadjuvant chemotherapy was decreased in community vs academic centers (borderline lumpectomy candidates: adjusted risk ratio = 0.73; 95% CI, 0.69-0.77; locally advanced disease: adjusted risk ratio = 0.78; 95% CI, 0.74-0.83). Use of guideline-concordant neoadjuvant chemotherapy is significantly higher among women treated at academic vs community centers in young and healthy women who do not commonly have contraindications to this treatment. Our study identified a potential disparity in cancer care by type of center where patients receive treatment. Copyright © 2016 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

  10. 3 d printing of 2 d N=(0,2) gauge theories

    NASA Astrophysics Data System (ADS)

    Franco, Sebastián; Hasan, Azeem

    2018-05-01

    We introduce 3 d printing, a new algorithm for generating 2 d N=(0,2) gauge theories on D1-branes probing singular toric Calabi-Yau 4-folds using 4 d N=1 gauge theories on D3-branes probing toric Calabi-Yau 3-folds as starting points. Equivalently, this method produces brane brick models starting from brane tilings. 3 d printing represents a significant improvement with respect to previously available tools, allowing a straightforward determination of gauge theories for geometries that until now could only be tackled using partial resolution. We investigate the interplay between triality, an IR equivalence between different 2 d N=(0,2) gauge theories, and the freedom in 3 d printing given an underlying Calabi-Yau 4-fold. Finally, we present the first discussion of the consistency and reduction of brane brick models.

  11. An acquired HER2 T798I gatekeeper mutation induces resistance to neratinib in a patient with HER2 mutant-driven breast cancer

    PubMed Central

    Hanker, Ariella B.; Brewer, Monica Red; Sheehan, Jonathan H.; Koch, James P.; Sliwoski, Gregory R.; Nagy, Rebecca; Lanman, Richard; Berger, Michael F.; Hyman, David M.; Solit, David B.; He, Jie; Miller, Vincent; Cutler, Richard E.; Lalani, Alshad S.; Cross, Darren; Lovly, Christine M.; Meiler, Jens; Arteaga, Carlos L.

    2017-01-01

    We report a HER2T798I gatekeeper mutation in a patient with HER2L869R-mutant breast cancer with acquired resistance to neratinib. Laboratory studies suggested that HER2L869R is a neratinib-sensitive, gain-of-function mutation that upon dimerization with mutant HER3E928G, also present in the breast cancer, amplifies HER2 signaling. The patient was treated with neratinib and exhibited a sustained partial response. Upon clinical progression, HER2T798I was detected in plasma tumor cell-free DNA. Structural modeling of this acquired mutation suggested that the increased bulk of isoleucine in HER2T798I reduces neratinib binding. Neratinib blocked HER2-mediated signaling and growth in cells expressing HER2L869R but not HER2L869R/T798I. In contrast, afatinib and the osimertinib metabolite AZ5104 strongly suppressed HER2L869R/T798I-induced signaling and cell growth. Acquisition of HER2T798I upon development of resistance to neratinib in a breast cancer with an initial activating HER2 mutation suggests HER2L869R is a driver mutation. HER2T798I-mediated neratinib resistance may be overcome by other irreversible HER2 inhibitors like afatinib. PMID:28274957

  12. Patient survival and tumor characteristics associated with CHEK2:p.I157T - findings from the Breast Cancer Association Consortium.

    PubMed

    Muranen, Taru A; Blomqvist, Carl; Dörk, Thilo; Jakubowska, Anna; Heikkilä, Päivi; Fagerholm, Rainer; Greco, Dario; Aittomäki, Kristiina; Bojesen, Stig E; Shah, Mitul; Dunning, Alison M; Rhenius, Valerie; Hall, Per; Czene, Kamila; Brand, Judith S; Darabi, Hatef; Chang-Claude, Jenny; Rudolph, Anja; Nordestgaard, Børge G; Couch, Fergus J; Hart, Steven N; Figueroa, Jonine; García-Closas, Montserrat; Fasching, Peter A; Beckmann, Matthias W; Li, Jingmei; Liu, Jianjun; Andrulis, Irene L; Winqvist, Robert; Pylkäs, Katri; Mannermaa, Arto; Kataja, Vesa; Lindblom, Annika; Margolin, Sara; Lubinski, Jan; Dubrowinskaja, Natalia; Bolla, Manjeet K; Dennis, Joe; Michailidou, Kyriaki; Wang, Qin; Easton, Douglas F; Pharoah, Paul D P; Schmidt, Marjanka K; Nevanlinna, Heli

    2016-10-03

    P.I157T is a CHEK2 missense mutation associated with a modest increase in breast cancer risk. Previously, another CHEK2 mutation, the protein truncating c.1100delC has been associated with poor prognosis of breast cancer patients. Here, we have investigated patient survival and characteristics of breast tumors of germ line p.I157T carriers. We included in the analyses 26,801 European female breast cancer patients from 15 studies participating in the Breast Cancer Association Consortium. We analyzed the association between p.I157T and the clinico-pathological breast cancer characteristics by comparing the p.I157T carrier tumors to non-carrier and c.1100delC carrier tumors. Similarly, we investigated the p.I157T associated risk of early death, breast cancer-associated death, distant metastasis, locoregional relapse and second breast cancer using Cox proportional hazards models. Additionally, we explored the p.I157T-associated genomic gene expression profile using data from breast tumors of 183 Finnish female breast cancer patients (ten p.I157T carriers) (GEO: GSE24450). Differential gene expression analysis was performed using a moderated t test. Functional enrichment was investigated using the DAVID functional annotation tool and gene set enrichment analysis (GSEA). The tumors were classified into molecular subtypes according to the St Gallen 2013 criteria and the PAM50 gene expression signature. P.I157T was not associated with increased risk of early death, breast cancer-associated death or distant metastasis relapse, and there was a significant difference in prognosis associated with the two CHEK2 mutations, p.I157T and c.1100delC. Furthermore, p.I157T was associated with lobular histological type and clinico-pathological markers of good prognosis, such as ER and PR expression, low TP53 expression and low grade. Gene expression analysis suggested luminal A to be the most common subtype for p.I157T carriers and CDH1 (cadherin 1) target genes to be significantly

  13. MTHFR 677C>T Polymorphism and the Risk of Breast Cancer: Evidence from an Original Study and Pooled Data for 28031 Cases and 31880 Controls

    PubMed Central

    Sekhar, Deepa; Francis, Amirtharaj; Gupta, Nishi; Konwar, Rituraj; Kumar, Sandeep; Kumar, Surender; Thangaraj, Kumarasamy; Rajender, Singh

    2015-01-01

    Background Methylenetetrahydrofolate reductase (MTHFR) acts at an important metabolic point in the regulation of cellular methylation reaction. It assists in the conversion of 5, 10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. The latter aids in remethylation of homocysteine to de novo methionine that is required for DNA synthesis. The objective of this study was to examine the effect of MTHFR 677 C>T polymorphism on the risk of breast cancer in the Indian sub-continent. Methods and Results We genotyped 677 C>T locus in 1096 individuals that were classified into cases (N=588) and controls (N=508). Genotype data were analyzed using chi-square test. No significant difference was observed in the distribution of genotypes between cases and controls in north Indian (P = 0.932), south Indian (P = 0.865), and pooled data (P = 0.680). To develop a consensus regarding the impact of 677C>T polymorphism on breast cancer risk, we also conducted a meta-analysis on 28031 cases and 31880 controls that were pooled from sixty one studies. The overall summary estimate upon meta-analysis suggested no significant correlation between the 677C>T substitution and breast cancer in the dominant model (Fixed effect model: OR = 0.97, P=0.072, Random effects model: OR = 0.96, P = 0.084) or the recessive model (Fixed effect model: OR = 1.05, P = 0.089; Random effects model: OR= 1.08, P= 0.067). Conclusion 677 C>T substitution does not affect breast cancer risk in the Indo-European and Dravidian populations of India. Analysis on pooled data further ruled out association between the 677 C>T polymorphism and breast cancer. Therefore, 677 C>T substitution does not appear to influence the risk of breast cancer. PMID:25803740

  14. Carcinoma of the larynx: role of laser surgery

    NASA Astrophysics Data System (ADS)

    Inouye, Tetsuzo; Tanabe, Tetsuya; Nakanoboh, Manabu; Ohmae, Yukio; Ogura, Masami

    1995-05-01

    68 cases of glottic carcinomas (T1 53 and T2 15 cases) treated with CO2 laser or KTP/532 laser April 1982 through March 1992 were reviewed. The patients were followed up from 13 to 130 months (mean 60 months). The 3-year determinate survival rate was 100% and 5-year determinate survival rate was 100% for T1 and 80% for T2. The voice conservation rate was 97% for T1a, 83% for T1b, and 80% for T2 and vocal function was satisfactorily preserved for daily life. The results led to the following conclusions: (1) Glottic T1 carcinomas can be treated by laser surgery alone. (2) Lesions involving the anterior commissure can be treated by laser excision and vaporization. (3) Laser surgery followed by external radiation therapy for glottic T2 carcinomas improves the voice conservation rate.

  15. [Frequency of CHEK2 gene mutations in patients with breast cancer from the Republic of Bashkortostan].

    PubMed

    2014-01-01

    Several studies have shown, that mutation in CHEK2 gene can increase the risk of different cancers, including breast cancer (BC). Clearly, that character of mutations distribution in the defined regions is depended on genetic structure of the population. We conducted the screening of mutations c.1100delC, c.444 + 1G>A, de15395, p.I157T andIp.R145Win CHEK2 gene in patients with breast cancer (n = 977) and in control group (n = 1069) originating from the Republic of Bashkortostan. The mutation de15395 in CHEK2 gene was detected with frequency of 1,23% (12/977)in woman with BC and 0.09% (1/1069) in controls (OR:13.28, CI 95%: 1.72-102.33, p = 0.003). Mutations c.1100delC and c.444 + 1G>A were found in BC patients and controls with frequencies of 0.4%, 0.4% (4/977) and 0.09% (1/1069), 0.2% (2/1069), respectively. The missense mutation p.I157T in CHEK2 was found as the most common variant in two studied cohorts (approximately 5%), but differences did not achieved statistical significance. We found the ethnic specificity in distribution of truncating mutations, which occurs mainly among the women of Slavic origin. All three mutations were identified in women of Russian and Ukrainian ethnic origin. Mutations c.1100delC and c.444 + 1G>A in CHEK2 gene were not detected in Bashkirs and Tatars, but CHEK2 de15395 mutation was observed in Tatars.

  16. Association of genetic susceptibility variants for type 2 diabetes with breast cancer risk in women of European ancestry.

    PubMed

    Zhao, Zhiguo; Wen, Wanqing; Michailidou, Kyriaki; Bolla, Manjeet K; Wang, Qin; Zhang, Ben; Long, Jirong; Shu, Xiao-Ou; Schmidt, Marjanka K; Milne, Roger L; García-Closas, Montserrat; Chang-Claude, Jenny; Lindstrom, Sara; Bojesen, Stig E; Ahsan, Habibul; Aittomäki, Kristiina; Andrulis, Irene L; Anton-Culver, Hoda; Arndt, Volker; Beckmann, Matthias W; Beeghly-Fadiel, Alicia; Benitez, Javier; Blomqvist, Carl; Bogdanova, Natalia V; Børresen-Dale, Anne-Lise; Brand, Judith; Brauch, Hiltrud; Brenner, Hermann; Burwinkel, Barbara; Cai, Qiuyin; Casey, Graham; Chenevix-Trench, Georgia; Couch, Fergus J; Cox, Angela; Cross, Simon S; Czene, Kamila; Dörk, Thilo; Dumont, Martine; Fasching, Peter A; Figueroa, Jonine; Flesch-Janys, Dieter; Fletcher, Olivia; Flyger, Henrik; Fostira, Florentia; Gammon, Marilie; Giles, Graham G; Guénel, Pascal; Haiman, Christopher A; Hamann, Ute; Harrington, Patricia; Hartman, Mikael; Hooning, Maartje J; Hopper, John L; Jakubowska, Anna; Jasmine, Farzana; John, Esther M; Johnson, Nichola; Kabisch, Maria; Khan, Sofia; Kibriya, Muhammad; Knight, Julia A; Kosma, Veli-Matti; Kriege, Mieke; Kristensen, Vessela; Le Marchand, Loic; Lee, Eunjung; Li, Jingmei; Lindblom, Annika; Lophatananon, Artitaya; Luben, Robert; Lubinski, Jan; Malone, Kathleen E; Mannermaa, Arto; Manoukian, Siranoush; Margolin, Sara; Marme, Frederik; McLean, Catriona; Meijers-Heijboer, Hanne; Meindl, Alfons; Miao, Hui; Muir, Kenneth; Neuhausen, Susan L; Nevanlinna, Heli; Neven, Patrick; Olson, Janet E; Perkins, Barbara; Peterlongo, Paolo; Phillips, Kelly-Anne; Pylkäs, Katri; Rudolph, Anja; Santella, Regina; Sawyer, Elinor J; Schmutzler, Rita K; Schoemaker, Minouk; Shah, Mitul; Shrubsole, Martha; Southey, Melissa C; Swerdlow, Anthony J; Toland, Amanda E; Tomlinson, Ian; Torres, Diana; Truong, Thérèse; Ursin, Giske; Van Der Luijt, Rob B; Verhoef, Senno; Wang-Gohrke, Shan; Whittemore, Alice S; Winqvist, Robert; Pilar Zamora, M; Zhao, Hui; Dunning, Alison M; Simard, Jacques; Hall, Per; Kraft, Peter; Pharoah, Paul; Hunter, David; Easton, Douglas F; Zheng, Wei

    2016-05-01

    Type 2 diabetes (T2D) has been reported to be associated with an elevated risk of breast cancer. It is unclear, however, whether this association is due to shared genetic factors. We constructed a genetic risk score (GRS) using risk variants from 33 known independent T2D susceptibility loci and evaluated its relation to breast cancer risk using the data from two consortia, including 62,328 breast cancer patients and 83,817 controls of European ancestry. Unconditional logistic regression models were used to derive adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) to measure the association of breast cancer risk with T2D GRS or T2D-associated genetic risk variants. Meta-analyses were conducted to obtain summary ORs across all studies. The T2D GRS was not found to be associated with breast cancer risk, overall, by menopausal status, or for estrogen receptor positive or negative breast cancer. Three T2D associated risk variants were individually associated with breast cancer risk after adjustment for multiple comparisons using the Bonferroni method (at p < 0.001), rs9939609 (FTO) (OR 0.94, 95 % CI = 0.92-0.95, p = 4.13E-13), rs7903146 (TCF7L2) (OR 1.04, 95 % CI = 1.02-1.06, p = 1.26E-05), and rs8042680 (PRC1) (OR 0.97, 95 % CI = 0.95-0.99, p = 8.05E-04). We have shown that several genetic risk variants were associated with the risk of both T2D and breast cancer. However, overall genetic susceptibility to T2D may not be related to breast cancer risk.

  17. Detection of prostate cancer in peripheral zone: comparison of MR diffusion tensor imaging, quantitative dynamic contrast-enhanced MRI, and the two techniques combined at 3.0 T.

    PubMed

    Li, Chunmei; Chen, Min; Li, Saying; Zhao, Xuna; Zhang, Chen; Luo, Xiaojie; Zhou, Cheng

    2014-03-01

    Previous studies have shown that the diagnostic accuracy for prostate cancer improved with diffusion tensor imaging (DTI) or quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) only. However, the efficacy of combined DTI and quantitative DCE-MRI in detecting prostate cancer at 3.0 T is still indeterminate. To investigate the utility of diffusion tensor imaging (DTI), quantitative DCE-MRI, and the two techniques combined at 3.0 T in detecting prostate cancer of the peripheral zone (PZ). DTI and DCE-MRI of 33 patients was acquired prior to prostate biopsy. Regions of interest (ROIs) were drawn according to biopsy zones which were apex, mid-gland, and base on each side of the PZ. Apparent diffusion coefficient (ADC), fractional anisotropy (FA), volume transfer constant (K(trans)), and rate constant (kep) values of cancerous sextants and non-cancerous sextants in PZ were calculated. Logistic regression models were generated for DTI, DCE-MRI, and DTI + DCE-MRI. Receiver-operating characteristic (ROC) curves were used to compare the ability of these models to differentiate cancerous sextants from non-cancerous sextants of PZ. There were significant differences in the ADC, FA, K(trans), and kep values between cancerous sextants and non-cancerous sextants in PZ (P < 0.0001, P < 0.0001, P < 0.0001, and P < 0.0001, respectively). The area under curve (AUC) for DTI + DCE-MRI was significantly greater than that for either DTI (0.93 vs. 0.86, P = 0.0017) or DCE-MRI (0.93 vs. 0.84, P = 0.0034) alone. The combination of DTI and quantitative DCE-MRI has better diagnostic performance in detecting prostate cancer of the PZ than either technique alone.

  18. LETTER TO THE EDITOR: Cross sections of 6Li(t,d1)7Li*[0.478] and 6Li(t,p1)8Li*[0.981] nuclear reactions in the 0-2 MeV energy range

    NASA Astrophysics Data System (ADS)

    Voronchev, V. T.; Kukulin, V. I.

    2000-12-01

    An original extrapolation technique developed previously is modified and applied to study nuclear reactions in the 6Li + T system at energies E = 0-2 MeV. Cross sections of gamma-ray-producing reactions 6Li(t,d1)7Li*[0.478] and 6Li(t,p1)8Li*[0.981] with important diagnostic implications are calculated. The (t,d1) nuclear data found exceed those accepted elsewhere by 2.5-3.5 times at sub-barrier energies. The cross sections of the (t,p1) reaction are calculated for the first time.

  19. The association between MMP2 -1306 C > T (rs243865) polymorphism and risk of prostate cancer.

    PubMed

    Shajarehpoor Salavati, L; Tafvizi, F; Manjili, H K

    2017-02-01

    Prostate cancer is the second most common cancer in men. Matrix metalloproteinase-2 (MMP2) is the most important member of the matrix metalloproteinase family. MMP2 digests the basement membrane and causes changes in the extracellular matrix which in turn facilitate cancer invasion. It, therefore, has a major role in tumor angiogenesis. Previous studies have identified a single-nucleotide polymorphism C/T at position -1306 of MMP2 gene promoter which is a key regulatory factor in cancer progression. The present study aimed to determine the association between MMP2 polymorphism and the risk of prostate cancer in Iranian men. This case-control study was performed on 50 paraffin-embedded prostate cancer tissue samples and 54 blood samples from healthy men. Genotyping of the samples was performed using high-resolution melting analysis (HRM). Finally, 20 % of the genotypes were confirmed by sequencing. No significant associations were found between CT and TT genotypes and the risk of prostate cancer. However, there were no significant relationships between the genotypes and the studied factors, e.g., age, pathological stage, and Gleason Score. MMP2 -1306 C > T (rs243865) polymorphism was not significantly related with prostate cancer susceptibility in Iranian men.

  20. Gene delivery of TIPE2 inhibits breast cancer development and metastasis via CD8+ T and NK cell-mediated antitumor responses.

    PubMed

    Zhang, Zhenhua; Liu, Li; Cao, Shousong; Zhu, Yizhun; Mei, Qibing

    2017-05-01

    Breast cancer is the second leading cause of cancer-related deaths in the female patients which was mainly caused by metastasis. Development of target gene therapy for breast cancer to suppress tumor progress and metastasis will improve the therapeutic options and be of great benefit to the patients. Tumor necrosis factor-alpha-induced protein 8-like 2 is a novel molecule for maintaining immune homeostasis and is involved in cancer development. In the present study, we overexpressed TIPE2 in breast cancer cells to investigate the role of TIPE2 in the development of breast cancer. Our results showed that overexpression of TIPE2 significantly inhibited the proliferation of 4T1 cells in vitro and in vivo. We constructed a non-viral targeted gene therapeutic system by using the minicircle plasmids expressing TIPE2. We found that the growth and metastasis of breast cancer was significantly inhibited by hydrodynamic gene delivery of TIPE2 plasmids in vivo. Mechanistically, TIPE2 increased T and NK cells, and decreased MDSCs. Gene delivery of TIPE2 up-regulated the production of IFN-γ and TNF-α by CD8 + T and NK cells in spleens and tumor microenvironment, and enhanced the cytotoxic activity of CD8 + T and NK cells. Taken together, TIPE2 inhibited breast cancer development and metastasis possibly via promoting CD8 + T and NK cell-mediated antitumor immune responses. Thus, the results indicate that TIPE2 may be a potential therapeutic target for breast cancer therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Cancer of the esophagus and esophagogastric junction: data-driven staging for the seventh edition of the American Joint Committee on Cancer/International Union Against Cancer Cancer Staging Manuals.

    PubMed

    Rice, Thomas W; Rusch, Valerie W; Ishwaran, Hemant; Blackstone, Eugene H

    2010-08-15

    Previous American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) stage groupings for esophageal cancer have not been data driven or harmonized with stomach cancer. At the request of the AJCC, worldwide data from 3 continents were assembled to develop data-driven, harmonized esophageal staging for the seventh edition of the AJCC/UICC cancer staging manuals. All-cause mortality among 4627 patients with esophageal and esophagogastric junction cancer who underwent surgery alone (no preoperative or postoperative adjuvant therapy) was analyzed by using novel random forest methodology to produce stage groups for which survival was monotonically decreasing, distinctive, and homogeneous. For lymph node-negative pN0M0 cancers, risk-adjusted 5-year survival was dominated by pathologic tumor classification (pT) but was modulated by histopathologic cell type, histologic grade, and location. For lymph node-positive, pN+M0 cancers, the number of cancer-positive lymph nodes (a new pN classification) dominated survival. Resulting stage groupings departed from a simple, logical arrangement of TNM. Stage groupings for stage I and II adenocarcinoma were based on pT, pN, and histologic grade; and groupings for squamous cell carcinoma were based on pT, pN, histologic grade, and location. Stage III was similar for histopathologic cell types and was based only on pT and pN. Stage 0 and stage IV, by definition, were categorized as tumor in situ (Tis) (high-grade dysplasia) and pM1, respectively. The prognosis for patients with esophageal and esophagogastric junction cancer depends on the complex interplay of TNM classifications as well as nonanatomic factors, including histopathologic cell type, histologic grade, and cancer location. These features were incorporated into a data-driven staging of these cancers for the seventh edition of the AJCC/UICC cancer staging manuals. Copyright (c) 2010 American Cancer Society.

  2. Indoleamine 2,3-dioxygenase 1 and overall survival of patients diagnosed with esophageal cancer

    PubMed Central

    Rosenberg, Ari J.; Wainwright, Derek A.; Rademaker, Alfred; Galvez, Carlos; Genet, Matthew; Zhai, Lijie; Lauing, Kristen L.; Mulcahy, Mary F.; Hayes, John P.; Odell, David D.; Horbinski, Craig; Komanduri, Srinadh; Tetreault, Marie-Pier; Kim, Kwang-Youn A.; Villaflor, Victoria M.

    2018-01-01

    Background Indoleamine 2,3-dioxygenase 1 (IDO1) is an enzyme with immunomodulatory properties that has emerged as a potential immunotherapeutic target in human cancer. However, the role, expression pattern, and relevance of IDO1 in esophageal cancer (EC) are poorly understood. Here, we utilize gene expression analysis of the cancer genome atlas (TCGA) and immunohistochemistry (IHC) to better understand the role and prognostic significance of IDO1 in EC. Results High IDO1 mRNA levels were associated with worse overall survival (OS) in both esophageal squamous cell carcinoma (SCC) (P = 0.02) and adenocarcinoma (AC) (P = 0.036). High co-expression of IDO1 and programmed death ligand 1 (PD-L1) was associated with worse OS in SCC (P = 0.0031) and AC (P = 0.0186). IHC for IDO1 in SCC showed a significant correlation with PD-L1 (P < 0.0001) and CD3ε (P < 0.0001). Conclusions EC with high IDO1 and PD-L1 expression is significantly correlated with decreased patient survival, and may correlate with increased T-cells. These data suggest that simultaneous inhibition of IDO1 and PD-(L)1 may overcome important barriers to T-cell mediated immune rejection of EC. Materials and Methods mRNA expression data from TCGA (SCC N = 87; AC N = 97). IHC in a second cohort of EC (N = 93) were stained for IDO1, PD-L1, and CD3ε, followed by light microscopic analysis. PMID:29805749

  3. Perovskite-type La0.8Sr0.2Co0.8Fe0.2O3 with uniform dispersion on N-doped reduced graphene oxide as an efficient bi-functional Li-O2 battery cathode.

    PubMed

    Cheng, Junfang; Jiang, Yuexing; Zhang, Ming; Zou, Lu; Huang, Yizhen; Wang, Ziling; Chi, Bo; Pu, Jian; Li, Jian

    2017-04-19

    A composite cathode including N-rGO with homogeneously dispersed perovskite La 0.8 Sr 0.2 Co 0.8 Fe 0.2 O 3 on the surface is studied. Li-O 2 batteries with LSCF@N-rGO cathode show better performance than those with LSCF-SP or N-rGO cathode. EIS and morphology analysis indicate that LSCF is beneficial to remold the shape of Li 2 O 2 and catalyze the decomposition of Li 2 O 2 .

  4. Low-temperature transport properties of TaxN thin films (0.72 <= x <= 0.83)

    NASA Astrophysics Data System (ADS)

    Očko, Miroslav; Žonja, Sanja; Nelson, G. L.; Freericks, J. K.; Yu, Lei; Newman, N.

    2010-11-01

    We report on low-temperature (4-320 K) transport properties of TaxN thin films deposited on an amorphous SiO2 substrate. In this work, TaxN thin films were restricted to a narrow range of x: 0.72 <= x <= 0.83 yet show considerable and nonmonotonic variation of their transport properties with Ta concentration. This behaviour is consistent with a local minimum in the density of electronic states at the Fermi level, as calculated for the rock salt intermetallic Ta4N5, and a rigid band model for describing the transport. The temperature dependence of the resistivity is best fit to the unusual form exp(-T/T0). Interestingly enough, the fit parameter T0 correlates well with the temperature of the maximum of the corresponding thermopower. Both of these characteristics, the fit and the correlation with the thermopower, are consistent with the Jonson-Mahan many-body formalism for charge and thermal transport when one has a nontrivial temperature dependence of the chemical potential. At the lowest temperatures measured, we have also found that the resistivity and thermopower show signatures of electron-electron interactions. We discuss also our results in the light of some theories usually used for describing transport of thin films and to other experimental investigations that have been performed on TaxN.

  5. Mobile Breast Cancer e-Support Program for Chinese Women With Breast Cancer Undergoing Chemotherapy (Part 2): Multicenter Randomized Controlled Trial.

    PubMed

    Zhu, Jiemin; Ebert, Lyn; Liu, Xiangyu; Wei, Di; Chan, Sally Wai-Chi

    2018-04-30

    Women undergoing chemotherapy for the treatment of breast cancer have frequently reported unmet supportive care needs. Moreover, easily accessible and innovative support is lacking. The purpose of this trial was to determine the effectiveness of an app-based breast cancer e-support program to address women's self-efficacy (primary outcome), social support, symptom distress, quality of life, anxiety, and depression. Secondary objectives included exploring the association between women's health outcomes and the breast cancer e-support usage data. A multicenter, single-blinded, randomized controlled trial was conducted. A total of 114 women with breast cancer, who were commencing chemotherapy and were able to access internet through a mobile phone, were recruited in the clinics from 2 university-affiliated hospitals in China. Women were randomized either to the intervention group (n=57) receiving breast cancer e-support plus care as usual or the control group (n=57) receiving care as usual alone. The health care team and research assistants collecting data were blinded to the women's group allocation. Bandura's self-efficacy theory and the social exchange theory guided the development of the breast cancer e-support program, which has 4 components: (1) a Learning forum, (2) a Discussion forum, (3) an Ask-the-Expert forum, and (4) a Personal Stories forum. Moderated by an experienced health care professional, the breast cancer e-support program supported women for 12 weeks covering 4 cycles of chemotherapy. Health outcomes were self-assessed through paper questionnaires in clinics at baseline before randomization (T0), after 3 (T1), and 6 months (T2) of follow-ups. Fifty-five participants in the intervention group and 49 in the control group completed the follow-up assessments (response rate: 91.2%). During the 12-week intervention, the log-in frequency ranged from 0 to 774 times (mean 54.7; SD 131.4; median 11; interquartile range, IQR 5-27), and the total usage

  6. N-substituted 8-aminopentacyclo[5.4.0.0(2,6).0(3,10).0(5,9)]undecanes as σ receptor ligands with potential neuroprotective effects.

    PubMed

    Banister, Samuel D; Manoli, Miral; Barron, Melissa L; Werry, Eryn L; Kassiou, Michael

    2013-10-01

    Several libraries of similarly N-substituted 8-aminopentacyclo[5.4.0.0(2,6).0(3,10).0(5,9)]undecanes (9), N-methyl-8-aminopentacyclo[5.4.0.0(2,6).0(3,10).0(5,9)]undecanes (14), and N-methyl-11-aminopentacyclo[5.4.0.0(2,6).0(3,10).0(5,9)]undecan-8-ones (13) were synthesised and screened against a panel of CNS targets in order to develop structure-affinity relationships for cage-modified trishomocubane σ receptor ligands based on the N-substituted 4-azahexacyclo[5.4.1.0(2,6).0(3,10).0(5,9).0(8,11)]dodecan-3-ol (8) scaffold. In general, compared to the corresponding 4-azahexacyclo[5.4.1.0(2,6).0(3,10).0(5,9).0(8,11)]dodecan-3-ols, compounds of type 9 were potent σ receptor ligands with low levels of subtype selectivity, while the corresponding N-methyl-8-aminopentacyclo[5.4.0.0(2,6).0(3,10).0(5,9)]undecanes showed reduced affinity but greater selectivity for σ2 receptors. The N-methyl-11-aminopentacyclo[5.4.0.0(2,6).0(3,10).0(5,9)]undecan-8-ones demonstrated the poorest σ receptor affinities, suggesting that 4-azahexacyclo[5.4.1.0(2,6).0(3,10).0(5,9).0(8,11)]dodecan-3-ols interact with σ receptors in the bridged hemiaminal form rather than as the non-transannular, aminoketone tautomers. Several compounds of type 8, 9, and 14 were assessed for their ability to inhibit nitric oxide release in vitro, and demonstrated comparable or greater efficacy than 4-phenyl-1-(4-phenylbutyl)piperidine (PPBP), an established neuroprotective σ ligand with NOS inhibitory activity. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. The risk of gastric cancer in carriers of CHEK2 mutations.

    PubMed

    Teodorczyk, Urszula; Cybulski, Cezary; Wokołorczyk, Dominika; Jakubowska, Anna; Starzyńska, Teresa; Lawniczak, Małgorzata; Domagała, Paweł; Ferenc, Katarzyna; Marlicz, Krzysztof; Banaszkiewicz, Zbigniew; Wiśniowski, Rafał; Narod, Steven A; Lubiński, Jan

    2013-09-01

    CHEK2 is a tumor suppressor gene whose functions are central to the induction of cell cycle arrest and apoptosis following DNA damage. Mutations in CHEK2 have been associated with cancers at many sites, including breast and prostate cancers, but the relationship between CHEK2 and gastric cancer has not been extensively studied. In Poland, there are four known founder alleles of CHEK2; three alleles are protein truncating (1100delC, IVS2G>A, del5395) and the other is a missense variant (I157T). We examined the frequencies of four Polish founder mutations in the CHEK2 gene in 658 unselected gastric cancer patients, in 154 familial gastric cancer patients and in 8,302 controls. A CHEK2 mutation was seen in 57 of 658 (8.7 %) unselected patients with gastric cancer compared to 480 of 8,302 (5.8 %) controls (OR 1.6, p = 0.004). A CHEK2 mutation was present in 19 of 154 (12.3 %) familial cases (OR = 2.3, p = 0.001). The odds ratio for early onset (<50 years) gastric cancer was higher (2.1, p = 0.01), than for cases diagnosed at age of 50 or above (OR 1.4, p = 0.05). Truncating mutations of CHEK2 were associated with higher risk (OR = 2.1, p = 0.02) than the missense mutation I157T (OR = 1.4, p = 0.04). CHEK2 mutations predispose to gastric cancer, in particular to young-onset cases.

  8. Invariant Natural Killer T Cell Deficiency and Functional Impairment in Sleep Apnea: Links to Cancer Comorbidity.

    PubMed

    Gaoatswe, Gadintshware; Kent, Brian D; Corrigan, Michelle A; Nolan, Geraldine; Hogan, Andrew E; McNicholas, Walter T; O'Shea, Donal

    2015-10-01

    Emerging evidence links obstructive sleep apnea (OSA) with increased cancer incidence and mortality. Invariant natural killer T (iNKT) cells play an important role in cancer immunity. We hypothesized that patients with OSA have low number of circulating invariant natural killer T (iNKT) cells, which may also be functionally impaired. This study aims to evaluate the frequency of circulating iNKT cells in OSA. We evaluated the frequency of circulating iNKT cells by flow cytometry in 33 snorers being assessed for possible OSA. Using iNKT cell lines, we also evaluated the effect of exposure to hypoxia over 24 hours on apoptosis, cytotoxicity, and cytokine production. Teaching hospital based sleep unit and research laboratory. Thirty-three snorers were evaluated: 9 with no OSA (apnea-hypopnea frequency [AHI] < 5/h), 12 with mild-moderate OSA (AHI 5-30) and 12 with severe OSA (AHI > 30). Patients with severe OSA had considerably fewer iNKT cells (0.18%) compared to patients with mild-moderate (0.24%) or no OSA (0.35%), P = 0.0026. The frequency of iNKT cells correlated negatively with apnea-hypopnea index (r = -0.58, P = 0.001), oxygen desaturation index (r = -0.58, P = 0.0003), and SpO2% < 90% (r = -0.5407, P = 0.005). The frequency of iNKT cells increased following 12 months of nCPAP therapy (P = 0.015). Hypoxia resulted in increased apoptosis (P = 0.016) and impaired cytotoxicity (P = 0.035). Patients with obstructive sleep apnea (OSA) have significantly reduced levels of circulating invariant natural killer T (iNKT) cells and hypoxia leads to impaired iNKT cell function. These observations may partly explain the increased cancer risk reported in patients with OSA. © 2015 Associated Professional Sleep Societies, LLC.

  9. Metallic 1T-LixMoS2 Cocatalyst Significantly Enhanced the Photocatalytic H2 Evolution over Cd0.5Zn0.5S Nanocrystals under Visible Light Irradiation.

    PubMed

    Du, Hong; Guo, Hong-Li; Liu, Ya-Nan; Xie, Xiao; Liang, Kuang; Zhou, Xiao; Wang, Xin; Xu, An-Wu

    2016-02-17

    In the present work, metallic 1T-LixMoS2 is utilized as a novel cocatalyst for Cd0.5Zn0.5S photocatalyst. The obtained LixMoS2/Cd0.5Zn0.5S hybrids show excellent photocatalytic performance for H2 generation from aqueous solution containing Na2S and Na2SO3 under splitting visible light illumination (λ ≥ 420 nm) without precious metal cocatalysts. It turns out that a certain amount of intercalating Li(+) ions ultimately drives the transition of MoS2 crystal from semiconductor triagonal phase (2H phase) to metallic phase (1T phase). The distinct properties of 1T-LixMoS2 promote the efficient separation of photoexcited electrons and holes when used as cocatalyst for Cd0.5Zn0.5S photocatalyst. As compared to 2H-MoS2 nanosheets only having edge active sites, photoinduced electrons not only transfer to the edge sites of 1T-LixMoS2, but also to the plane active sites of 1T-LixMoS2 nanosheets. The content of LixMoS2 in hybrid photocatalysts influences the photocatalytic activity. The optimal 1T-LixMoS2 (1.0 wt %)/Cd0.5Zn0.5S nanojunctions display the best activity for hydrogen production, achieving a hydrogen evolution rate of 769.9 μmol h(-1), with no use of noble metal loading, which is about 3.5 times higher than that of sole Cd0.5Zn0.5S, and 2 times higher than that of 2H-MoS2 (1.0 wt %)/Cd0.5Zn0.5S samples. Our results demonstrate that Li(+)-intercalated MoS2 nanosheets with high conductivity, high densities of active sites, low cost, and environmental friendliness are a prominent H2 evolution cocatalyst that might substitute for noble metal for potential hydrogen energy applications.

  10. Impact of pathologic diagnosis of internal mammary lymph node metastasis in clinical N2b and N3b breast cancer patients.

    PubMed

    Joo, Ji Hyeon; Kim, Su Ssan; Ahn, Seung-Do; Choi, Eun Kyung; Jung, Jin Hong; Jeong, Yuri; Ahn, Sei Hyun; Son, Byung Ho; Lee, Jong Won; Kim, Hee Jung; Go, Beom Seok; Kim, Hak Hee; Cha, Joo Hee; Shin, Hee Jung; Chae, Eun Young

    2017-11-01

    To analyze the prognostic role of pathologic confirmation of internal mammary lymph nodes (IMNs) for breast cancer patients who received neoadjuvant chemotherapy. Of the patients who were treated with neoadjuvant chemotherapy, surgery, and radiation therapy between 2009 and 2013, 114 women had suspicious IMNs and FNAB was attempted. Clinical IMN metastasis was diagnosed by 18F-FDG PET/CT positivity or pathologic confirmation (N = 70). Patients were divided into the FNAB(+) or FNAB(-) IMN group. The pathologic confirmation rate was 57% (40 of 70 patients). Rates were 74% in US-positive, 70% in MRI-positive, and 55% in PET-positive patients. Nodal stage was cN2b (6%) or cN3b (94%). Five-year progression-free survival (PFS) was significantly worse in patients with FNAB(+) IMN metastasis than FNAB(-) IMN metastasis (61% vs. 87%, P = 0.03). FNAB(+) IMN patients showed worse distant metastasis and regional recurrence-free survival without statistical significance (69% vs. 86%, P = 0.06, and 81% vs. 96%, P = 0.06). With median follow-up of 50.5 months (13.0-97.0 months), overall survival at 5 years was 77%, and PFS was 72%. Patients with FNAB-proven IMN metastasis had worse treatment outcomes compared to patients with clinically diagnosed IMN metastasis in cN2b/N3b breast cancer.

  11. Association of Genetic Susceptibility Variants for Type 2 Diabetes with Breast Cancer Risk in Women of European Ancestry

    PubMed Central

    Zhao, Zhiguo; Wen, Wanqing; Michailidou, Kyriaki; Bolla, Manjeet K.; Wang, Qin; Zhang, Ben; Long, Jirong; Shu, Xiao-Ou; Schmidt, Marjanka K.; Milne, Roger L.; García-Closas, Montserrat; Chang-Claude, Jenny; Lindstrom, Sara; Bojesen, Stig E.; Ahsan, Habibul; Aittomäki, Kristiina; Andrulis, Irene L.; Anton-Culver, Hoda; Arndt, Volker; Beckmann, Matthias W.; Beeghly-Fadiel, Alicia; Benitez, Javier; Blomqvist, Carl; Bogdanova, Natalia V.; Børresen-Dale, Anne-Lise; Brand, Judith; Brauch, Hiltrud; Brenner, Hermann; Burwinkel, Barbara; Cai, Qiuyin; Casey, Graham; Chenevix-Trench, Georgia; Couch, Fergus J.; Cox, Angela; Cross, Simon S.; Czene, Kamila; Dörk, Thilo; Dumont, Martine; Fasching, Peter A.; Figueroa, Jonine; Flesch-Janys, Dieter; Fletcher, Olivia; Flyger, Henrik; Fostira, Florentia; Gammon, Marilie; Giles, Graham G.; Guénel, Pascal; Haiman, Christopher A.; Hamann, Ute; Harrington, Patricia; Hartman, Mikael; Hooning, Maartje J.; Hopper, John L.; Jakubowska, Anna; Jasmine, Farzana; John, Esther M.; Johnson, Nichola; Kabisch, Maria; Khan, Sofia; Kibriya, Muhammad; Knight, Julia A.; Kosma, Veli-Matti; Kriege, Mieke; Kristensen, Vessela; Le Marchand, Loic; Lee, Eunjung; Li, Jingmei; Lindblom, Annika; Lophatananon, Artitaya; Luben, Robert; Lubinski, Jan; Malone, Kathleen E.; Mannermaa, Arto; Manoukian, Siranoush; Margolin, Sara; Marme, Frederik; McLean, Catriona; Meijers-Heijboer, Hanne; Meindl, Alfons; Miao, Hui; Muir, Kenneth; Neuhausen, Susan L.; Nevanlinna, Heli; Neven, Patrick; Olson, Janet E.; Perkins, Barbara; Peterlongo, Paolo; Phillips, Kelly-Anne; Pylkäs, Katri; Rudolph, Anja; Santella, Regina; Sawyer, Elinor J.; Schmutzler, Rita K.; Schoemaker, Minouk; Shah, Mitul; Shrubsole, Martha; Southey, Melissa C.; Swerdlow, Anthony J; Toland, Amanda E.; Tomlinson, Ian; Torres, Diana; Truong, Thérèse; Ursin, Giske; Van Der Luijt, Rob B.; Verhoef, Senno; Wang-Gohrke, Shan; Whittemore, Alice S.; Winqvist, Robert; Zamora, M. Pilar; Zhao, Hui; Dunning, Alison M.; Simard, Jacques; Hall, Per; Kraft, Peter; Pharoah, Paul; Hunter, David; Easton, Douglas F.; Zheng, Wei

    2016-01-01

    Purpose Type 2 diabetes (T2D) has been reported to be associated with an elevated risk of breast cancer. It is unclear, however, whether this association is due to shared genetic factors. Methods We constructed a genetic risk score (GRS) using risk variants from 33 known independent T2D susceptibility loci and evaluated its relation to breast cancer risk using the data from two consortia, including 62,328 breast cancer patients and 83,817 controls of European ancestry. Unconditional logistic regression models were used to derive adjusted odds ratios (OR) and 95% confidence intervals (CI) to measure the association of breast cancer risk with T2D GRS or T2D-associated genetic risk variants. Meta-analyses were conducted to obtain summary ORs across all studies. Results The T2D GRS was not found to be associated with breast cancer risk, overall, by menopausal status, or for estrogen receptor positive or negative breast cancer. Three T2D associated risk variants were individually associated with breast cancer risk after adjustment for multiple comparisons using the Bonferroni method (at P < 0.001), rs9939609 (FTO) (OR = 0.94, 95% CI = 0.92 – 0.95, P = 4.13E-13), rs7903146 (TCF7L2) (OR = 1.04, 95% CI = 1.02 – 1.06, P = 1.26E-05), and rs8042680 (PRC1) (OR = 0.97, 95% CI = 0.95 – 0.99, P = 8.05E-04). Conclusions We have shown that several genetic risk variants were associated with the risk of both T2D and breast cancer. However, overall genetic susceptibility to T2D may not be related to breast cancer risk. PMID:27053251

  12. Induction of gamma delta T cells using zoledronate plus interleukin-2 in patients with metastatic cancer.

    PubMed

    Nagamine, Ichiro; Yamaguchi, Yoshiyuki; Ohara, Masahiro; Ikeda, Takuhiro; Okada, Morihito

    2009-03-01

    A loss of human leukocyte antigen (HLA) expression in clinical tumors is one of their escape mechanisms from immune attack by HLA-restricted effector cells. In this study, the induction of HLA-unrestricted effector cells, gamma delta T cells, using zoledronate (ZOL) and interleukin (IL)-2 in vitro was investigated in patients with metastatic cancer. Peripheral blood mononuclear cells (PBMCs) from 10 cancer patients (8 colorectal and 2 esophageal) with multiple metastases and ascites lymphocytes from 3 cancer patients (1 gastric and 2 colorectal) were stimulated with varied concentrations of ZOL plus 100 U/ml IL-2 for 48 hr followed by culturing with IL-2 alone for 12 days. Lymphocyte proliferative responses were determined using 3H-TdR uptakes and interferon (IFN)-gamma production was evaluated using enzyme-linked immunosorbent assay. Surface phenotyping was performed using flow cytometry. Cytotoxic activity of effector cells was determined using 51Cr-releasing assay. It was found that proliferative responses of PBMCs were significantly stimulated with ZOL plus IL-2 when compared with IL-2 alone, showing 200 to 500-fold expansions for 2 weeks, although ZOL alone induced no response. The optimal concentration of ZOL was 1-5 microM. Ascites lymphocytes could also be stimulated with ZOL plus IL-2. The proliferative responses were remarkable in patients whose PBMCs could produce high levels of IFN-gamma during an initial 48-hr stimulation using ZOL plus IL-2. Removal of an adherent cell fraction before the induction augmented the proliferative responses in patients who otherwise had low-grade proliferative responses. Generated cells comprising approximately 90 or 20% in PBMCs from healthy donors or cancer patients, respectively, expressed gamma delta-type T-cell receptor. Gamma delta T cells showed high cytotoxic activity against CD166-positive TE12 and TE13 cancer cells but not against CD166-negative MKN45 cells. The cytotoxic activity against TE13 cells was augmented

  13. T2 relaxation times of the glenohumeral joint at 3.0 T MRI in patients with and without primary and secondary osteoarthritis.

    PubMed

    Lee, So-Yeon; Park, Hee-Jin; Kwon, Heon-Ju; Kim, Mi Sung; Choi, Seon Hyeong; Choi, Yoon Jung; Kim, Eugene

    2015-11-01

    Quantitative magnetic resonance imaging (MRI) of cartilage has recently been applied to patients with osteoarthritis (OA). T2 mapping is a sensitive method of detecting changes in the chemical composition and structure of cartilage. To establish baseline T2 values of glenohumeral joint cartilage at 3.0T and compare T2 values among subjects with and without OA. The study involved 30 patients (18 women, 12 men; median age, 67 years; age range, 51-78 years) with primary (n = 7) and secondary OA (n = 23) in the glenohumeral joint and 34 subjects without OA (19 women, 15 men; median age, 49 years; age range, 23-63 years). All subjects were evaluated by radiography and 3.0T MRI including a multi-echo T2-weighted spin echo pulse sequence. The T2 value of the cartilage was measured by manually drawing the region of interest on the T2 map. Per-zone comparison of T2 values was performed using Mann-Whitney U test. Median T2 values differed significantly between subjects without OA (36.00 ms [interquartile range, 33.89-37.31 ms]) and those with primary (37.52 ms [36.84-39.11], P = 0.028), but not secondary (36.87 ms [34.70-41.10], P = 0.160) OA. Glenohumeral cartilage T2 values were higher in different zones between patients with primary and secondary OA than in subjects without OA. These T2 values can be used for comparison to assess cartilage degeneration in patients with shoulder OA. Significant differences in T2 were observed among subjects without OA and those with primary and secondary OA. © The Foundation Acta Radiologica 2014.

  14. Evaluation with 3.0-T MR imaging: predicting the pathological response of triple-negative breast cancer treated with anthracycline and taxane neoadjuvant chemotherapy.

    PubMed

    Kim, Min Jung; Kim, Eun-Kyung; Park, Seho; Moon, Hee Jung; Kim, Seung Il; Park, Byeong-Woo

    2015-09-01

    Triple-negative breast cancer (TNBC) which expresses neither hormonal receptors nor HER-2 is associated with poor prognosis and shorter survival. Several studies have suggested that TNBC patients attaining pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) show a longer survival than those without pCR. To assess the accuracy of 3.0-T breast magnetic resonance imaging (MRI) in predicting pCR and to evaluate the clinicoradiologic factors affecting the diagnostic accuracy of 3.0-T breast MRI in TNBC patients treated with anthracycline and taxane (ACD). This retrospective study was approved by the institutional review board; patient consent was not required. Between 2009 and 2012, 35 TNBC patients with 3.0-T breast MRI prior to (n = 26) or after (n = 35) NAC were included. MRI findings were reviewed according to pCR to chemotherapy. The diagnostic accuracy of 3.0-T breast MRI for predicting pCR and the clinicoradiological factors affecting MRI accuracy and response to NAC were analyzed. 3.0-T MRI following NAC with ACD accurately predicted pCR in 91.4% of TNBC patients. The residual tumor size between pathology and 3.0-T MRI in non-pCR cases showed a higher correlation in the Ki-67-positive TNBC group (r = 0.947) than in the Ki-67 negative group (r = 0.375) with statistical trends (P = 0.069). Pre-treatment MRI in the non-pCR group compared to the pCR group showed a larger tumor size (P = 0.030) and non-mass presentation (P = 0.015). 3.0-T MRI in TNBC patients following NAC with ACD showed a high accuracy for predicting pCR to NAC. Ki-67 can affect the diagnostic accuracy of 3.0-T MRI for pCR to NAC with ACD in TNBC patients. © The Foundation Acta Radiologica 2014.

  15. In-Bore 3-T MR-guided Transrectal Targeted Prostate Biopsy: Prostate Imaging Reporting and Data System Version 2–based Diagnostic Performance for Detection of Prostate Cancer

    PubMed Central

    Tan, Nelly; Lin, Wei-Chan; Khoshnoodi, Pooria; Asvadi, Nazanin H.; Yoshida, Jeffrey; Margolis, Daniel J. A.; Lu, David S. K.; Wu, Holden; Lu, David Y.; Huang, Jaioti

    2017-01-01

    Purpose To determine the diagnostic yield of in-bore 3-T magnetic resonance (MR) imaging–guided prostate biopsy and stratify performance according to Prostate Imaging Reporting and Data System (PI-RADS) versions 1 and 2. Materials and Methods This study was HIPAA compliant and institution review board approved. In-bore 3-T MR-guided prostate biopsy was performed in 134 targets in 106 men who (a) had not previously undergone prostate biopsy, (b) had prior negative biopsy findings with increased prostate-specific antigen (PSA) level, or (c) had a prior history of prostate cancer with increasing PSA level. Clinical, diagnostic 3-T MR imaging was performed with in-bore guided prostate biopsy, and pathology data were collected. The diagnostic yields of MR-guided biopsy per patient and target were analyzed, and differences between biopsy targets with negative and positive findings were determined. Results of logistic regression and areas under the curve were compared between PI-RADS versions 1 and 2. Results Prostate cancer was detected in 63 of 106 patients (59.4%) and in 72 of 134 targets (53.7%) with 3-T MR imaging. Forty-nine of 72 targets (68.0%) had clinically significant cancer (Gleason score ≥ 7). One complication occurred (urosepsis, 0.9%). Patients who had positive target findings had lower apparent diffusion coefficient values (875 × 10−6 mm2/sec vs 1111 × 10−6 mm2/sec, respectively; P < .01), smaller prostate volume (47.2 cm3 vs 75.4 cm3, respectively; P < .01), higher PSA density (0.16 vs 0.10, respectively; P < .01), and higher proportion of PI-RADS version 2 category 3–5 scores when compared with patients with negative target findings. MR targets with PI-RADS version 2 category 2, 3, 4, and 5 scores had a positive diagnostic yield of three of 23 (13.0%), six of 31 (19.4%), 39 of 50 (78.0%), and 24 of 29 (82.8%) targets, respectively. No differences were detected in areas under the curve for PI-RADS version 2 versus 1. Conclusion In-bore 3-T MR

  16. CT volumetry can potentially predict the local stage for gastric cancer after chemotherapy

    PubMed Central

    Wang, Zhi-Cong; Wang, Chen; Ding, Ying; Ji, Yuan; Zeng, Meng-Su; Rao, Sheng-Xiang

    2017-01-01

    PURPOSE We aimed to evaluate the value of CT tumor volumetry for predicting T and N stages of gastric cancer after chemotherapy, with pathologic results as the reference standard. METHODS This study retrospectively evaluated 42 patients diagnosed with gastric cancer, who underwent chemotherapy followed by surgery. Pre- and post-treatment CT tumor volumes (VT) were measured in portal venous phase and volume reduction ratios were calculated. Correlations between pre- and post-treatment VT, reduction ratio, and pathologic stages were analyzed. Receiver operator characteristic (ROC) analyses were also performed to assess diagnostic performance for prediction of downstaging to T02 stage and N0 stage. RESULTS Pretreatment VT, post-treatment VT, and VT reduction ratio were significantly correlated with T stage (rs=0.329, rs=0.546, rs= −0.422, respectively). Post-treatment VT and VT reduction ratio were significantly correlated with N stage (rs=0.442 and rs= −0.376, respectively). Pretreatment VT, post-treatment VT, and VT reduction ratio were significantly different between T02 and T3,4 stage tumors (P = 0.05, P < 0.001, and P = 0.002, respectively). The differences between N0 and ≥N1 groups were also statistically significant (P = 0.005 for post-treatment VT, P = 0.016 for VT reduction ratio, respectively). The area under the ROC curve (AUC) for identification of T02 groups was 0.70 for pretreatment VT, 0.88 for post-treatment VT, and 0.82 for VT reduction ratio, respectively. AUC was 0.78 for post-treatment VT and 0.74 for VT reduction ratio for identification of N0 groups. CONCLUSION CT tumor volumetry, particularly post-treatment measurement of VT, is potentially valuable for predicting histopathologic T and N stages after chemotherapy in patients with gastric cancer. PMID:28703101

  17. Neoadjuvant Chemoradiation for Distal Rectal Cancer: 5-Year Updated Results of a Randomized Phase 2 Study of Neoadjuvant Combined Modality Chemoradiation for Distal Rectal Cancer

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mohiuddin, Mohammed, E-mail: asemuddin@gmail.com; Paulus, Rebecca; Mitchell, Edith

    2013-07-01

    Purpose: To assess the efficacy of 2 different approaches to neoadjuvant chemoradiation for distal rectal cancers. Methods and Materials: One hundred six patients with T3/T4 distal rectal cancers were randomized in a phase 2 study. Patients received either continuous venous infusion (CVI) of 5-Fluorouracil (5-FU), 225 mg/m{sup 2} per day, 7 days per week plus pelvic hyperfractionated radiation (HRT), 45.6 Gy at 1.2 Gy twice daily plus a boost of 9.6 to 14.4 Gy for T3 or T4 cancers (Arm 1), or CVI of 5-FU, 225 mg/m{sup 2} per day, Monday to Friday, plus irinotecan, 50 mg/m{sup 2} once weeklymore » × 4, plus pelvic radiation therapy (RT), 45 Gy at 1.8 Gy per day and a boost of 5.4 Gy for T3 and 9 Gy for T4 cancers (Arm 2). Surgery was performed 4 to 10 weeks later. Results: All eligible patients (n=103) are included in this analysis; 2 ineligible patients were excluded, and 1 patient withdrew consent. Ninety-eight of 103 patients (95%) underwent resection. Four patients did not undergo surgery for either disease progression or patient refusal, and 1 patient died during induction chemotherapy. The median time of follow-up was 6.4 years in Arm 1 and 7.0 years in Arm 2. The pathological complete response (pCR) rates were 30% in Arm 1 and 26% in Arm 2. Locoregional recurrence rates were 16% in Arm 1 and 17% in Arm 2. Five-year survival rates were 61% and 75% and Disease-specific survival rates were 78% and 85% for Arm1 and Arm 2, respectively. Five second primaries occurred in patients on Arm 1, and 1 second primary occurred in Arm 2. Conclusions: High rates of disease-specific survival were seen in each arm. Overall survival appears affected by the development of unrelated second cancers. The high pCR rates with 5-FU and higher dose radiation in T4 cancers provide opportunity for increased R0 resections and improved survival.« less

  18. Antitumor effects and persistence of a novel HER2 CAR T cells directed to gastric cancer in preclinical models

    PubMed Central

    Han, Yali; Liu, Chuanyong; Li, Guanhua; Li, Juan; Lv, Xingyan; Shi, Huan; Liu, Jie; Liu, Shuai; Yan, Peng; Wang, Shuyun; Sun, Yuping; Sun, Meili

    2018-01-01

    New immunotherapeutic approaches are urgently needed for gastric cancer due to its poor survival and unsatisfactory treatment. Here we applied the humanized chA21 scfv based chimeric antigen receptor (CAR) modified T cells approach to the HER2 overexpressing gastric cancer treatment. The chA21-4-1BBz CAR T cells specifically exerted Th1 skewed cytokine response and efficient cytolysis of HER2 overexpressing human gastric cancer cells in vitro. Both the cytokine production and cytotoxicity levels were correlated with the level of HER2 surface expression by tumor cells. In established subcutaneous xenograft and peritoneal metastasis models, chA21-4-1BBz CAR T cells dramatically facilitated regression of HER2 overexpressing tumor and prolonged survival of tumor-bearing mice, whereas spared the progression of HER2 low-expressing tumor. Additionally, the capability of these CAR T cells to persist in circulation, as well as specifically home to, and accumulate in tumor sites were identified. Taken together, these results provide the basis for the future clinical investigation of the humanized chA21 scFv based, 4-1BB costimulated CAR T cells for the treatment of gastric cancer, and other HER2-expressing solid tumors. PMID:29416924

  19. Triple-Negative or HER2-Positive Status Predicts Higher Rates of Locoregional Recurrence in Node-Positive Breast Cancer Patients After Mastectomy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wang Shulian; Li Yexiong, E-mail: yexiong@yahoo.com; Song Yongwen

    2011-07-15

    Purpose: To evaluate the prognostic value of determining estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) expression in node-positive breast cancer patients treated with mastectomy. Methods and Materials: The records of 835 node-positive breast cancer patients who had undergone mastectomy between January 2000 and December 2004 were analyzed retrospectively. Of these, 764 patients (91.5%) received chemotherapy; 68 of 398 patients (20.9%) with T1-2N1 disease and 352 of 437 patients (80.5%) with T3-4 or N2-3 disease received postoperative radiotherapy. Patients were classified into four subgroups according to hormone receptor (Rec+ or Rec-) and HER2 expression profiles:more » Rec-/HER2- (triple negative; n = 141), Rec-/HER2+ (n = 99), Rec+/HER2+ (n = 157), and Rec+/HER2- (n = 438). The endpoints were the duration of locoregional recurrence-free survival, distant metastasis-free survival, disease-free survival, and overall survival. Results: Patients with triple-negative, Rec-/HER2+, and Rec+/HER2+ expression profiles had a significantly lower 5-year locoregional recurrence-free survival than those with Rec+/HER2- profiles (86.5% vs. 93.6%, p = 0.002). Compared with those with Rec+/HER2+ and Rec+/HER2- profiles, patients with Rec-/HER2- and Rec-/HER2+ profiles had significantly lower 5-year distant metastasis-free survival (69.1% vs. 78.5%, p = 0.000), lower disease-free survival (66.6% vs. 75.6%, p = 0.000), and lower overall survival (71.4% vs. 84.2%, p = 0.000). Triple-negative or Rec-/HER2+ breast cancers had an increased likelihood of relapse and death within the first 3 years after treatment. Conclusions: Triple-negative and HER2-positive profiles are useful markers of prognosis for locoregional recurrence and survival in node-positive breast cancer patients treated with mastectomy.« less

  20. Computer-aided detection of prostate cancer in T2-weighted MRI within the peripheral zone

    NASA Astrophysics Data System (ADS)

    Rampun, Andrik; Zheng, Ling; Malcolm, Paul; Tiddeman, Bernie; Zwiggelaar, Reyer

    2016-07-01

    In this paper we propose a prostate cancer computer-aided diagnosis (CAD) system and suggest a set of discriminant texture descriptors extracted from T2-weighted MRI data which can be used as a good basis for a multimodality system. For this purpose, 215 texture descriptors were extracted and eleven different classifiers were employed to achieve the best possible results. The proposed method was tested based on 418 T2-weighted MR images taken from 45 patients and evaluated using 9-fold cross validation with five patients in each fold. The results demonstrated comparable results to existing CAD systems using multimodality MRI. We achieved an area under the receiver operating curve (A z ) values equal to 90.0%+/- 7.6% , 89.5%+/- 8.9% , 87.9%+/- 9.3% and 87.4%+/- 9.2% for Bayesian networks, ADTree, random forest and multilayer perceptron classifiers, respectively, while a meta-voting classifier using average probability as a combination rule achieved 92.7%+/- 7.4% .

  1. Methyl transfer from Fe (and Mo) to Sn: formation of (eta(5)-C(5)H(5))M(CO)(n)Sn(t)Bu(2)Me (M = Fe, n = 2; M = Mo, n = 3) complexes from photochemical irradiation of (eta(5)-C(5)H(5))M(CO)(n)Me and (t)Bu(2)SnH(2).

    PubMed

    Sharma, Hemant K; Arias-Ugarte, Renzo; Metta-Magana, Alejandro; Pannell, Keith H

    2010-07-07

    Formation of an Sn-CH(3) bond, concomitantly with an Sn-M (M = Fe, Mo), is readily achieved from the photochemical reactions of (t)Bu(2)SnH(2) with (eta(5)-C(5)H(5))M(CO)(n)Me (M = Fe, n = 2; M = Mo, n = 3) via the intermediacy of (eta(5)-C(5)H(5))M(CO)(n)Sn(t)Bu(2)H.

  2. Programmed death-1 gene polymorphism (PD-1.5 C/T) is associated with gastric cancer.

    PubMed

    Savabkar, Sanaz; Azimzadeh, Pedram; Chaleshi, Vahid; Nazemalhosseini Mojarad, Ehsan; Aghdaei, Hamid Asadzadeh

    2013-01-01

    This study aimed to determine the association between PD-1.5C/T (rs2227981, +7785) and the risk of gastric cancer (GC) in an Iranian population. Gastric cancer is the fourth most common cancer in the world. The programmed death 1 (PD-1) is a member of the CD28 super family. PD-1 is a negative regulator of T-cell effector mechanisms which decrease immune responses against cancer. we conducted case- control study to investigate the association of PD-1.5 C/T polymorphism in 122 GC patients and 166 control individuals. DNA was extracted from blood specimens. Genotypes were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The frequency of CC, CT and TT genotypes was 53.6%, 42.2% and 4.2% in control group and 41%, 54.1% and 4.9% in gastric cancer patients respectively. CC genotype was more frequent in control individuals than in patients but we found no statically significant association. The frequencies of PD-1.5CT genotypes were significantly higher in GC patient compared with control individuals (OR= 1.77, 95% CI= 1.077-2.931; P=0.026). Allele distribution was similar in patients and healthy individuals (p = 0.061).Frequency of C and T alleles was 74.7%, 25.3% in control individuals and 68.03% and 31.97% in gastric cancer patients respectively. These results suggest that PD-1.5 C/T polymorphism may affect the GC risk and prognosis in an Iranian population.

  3. CT and 3-T MRI accurately identify T3c disease in colon cancer, which strongly predicts disease-free survival.

    PubMed

    Hunter, C; Siddiqui, M; Georgiou Delisle, T; Blake, H; Jeyadevan, N; Abulafi, M; Swift, I; Toomey, P; Brown, G

    2017-04-01

    To compare the preoperative staging accuracy of computed tomography (CT) and 3-T magnetic resonance imaging (MRI) in colon cancer, and to investigate the prognostic significance of identified risk factors. Fifty-eight patients undergoing primary resection of their colon cancer were prospectively recruited, with 53 patients included for final analysis. Accuracy of CT and MRI were compared for two readers, using postoperative histology as the reference standard. Patients were followed-up for a median of 39 months. Risk factors were compared by modality and reader in terms of metachronous metastases and disease-free survival (DFS), stratified for adjuvant chemotherapy. Accuracy for the identification of T3c+ disease was non-significantly greater on MRI (75% and 79%) than CT (70% and 77%). Differences in the accuracy of MRI and CT for identification of T3+ disease (MRI 75% and 57%, CT 72% and 66%) and N+ disease (MRI 62% and 63%, CT 62% and 56%) were also non-significant. Identification of extramural venous invasion (EMVI+) disease was significantly greater on MRI (75% and 75%) than CT (79% and 54%) for one reader (p=0.029). T3c+ disease at histopathology was the only risk factor that demonstrated a significant difference in rate of metachronous metastases (odds ratio [OR] 8.6, p=0.0044) and DFS stratified for adjuvant therapy (OR=4, p=0.048). T3c or greater disease is the strongest risk factor for predicting DFS in colon cancer, and is accurately identified on imaging. T3c+ disease may therefore be the best imaging entry criteria for trials of neoadjuvant treatment. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  4. Uncommon CHEK2 mis-sense variant and reduced risk of tobacco-related cancers: case control study.

    PubMed

    Brennan, Paul; McKay, James; Moore, Lee; Zaridze, David; Mukeria, Anush; Szeszenia-Dabrowska, Neonilia; Lissowska, Jolanta; Rudnai, Peter; Fabianova, Eleonora; Mates, Dana; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Chow, Wong-Ho; Rothman, Nathanial; Chabrier, Amelie; Gaborieau, Valerie; Odefrey, Fabrice; Southey, Melissa; Hashibe, Mia; Hall, Janet; Boffetta, Paolo; Peto, Julian; Peto, Richard; Hung, Rayjean J

    2007-08-01

    CHEK2 is a key cell cycle control gene encoding a pluripotent kinase that can cause arrest or apoptosis in response to unrepaired DNA damage. We report a large case-control study of a non-functional variant that had previously been expected to increase cancer rates. Four thousand and fifteen cancer patients (2250 lung, 811 squamous upper aero-digestive and 954 kidney) and 3052 controls in central Europe were genotyped for the mis-sense variant rs17879961 (replacement of T by C), which changes an amino acid (I157T) in an active site of the gene product. The heterozygous (T/C) genotype was associated with a highly significantly lower incidence of lung cancer than the common T/T genotype [relative risk (RR), T/C versus T/T, 0.44, with 95% confidence interval (CI) 0.31-0.63, P < 0.00001] and with a significantly lower incidence of upper aero-digestive cancer (RR 0.44, CI 0.26-0.73, P = 0.001; P = 0.000001 for lung or upper aero-digestive cancer). Protection was significantly greater for squamous than adenomatous lung cancer (P = 0.001). There was an increase of borderline significance in kidney cancer (RR 1.44, CI 0.99-2.00, P = 0.06). This unexpected halving of tobacco-related cancer (since replicated independently) implies much greater absolute risk reduction in smokers than in non-smokers. The mechanism is unknown: perhaps squamous stem cell apoptosis following smoke exposure causes net harm (e.g. by forcing nearby stem cells to divide before they have repaired their own DNA damage from tobacco smoke). If so, reducing the rate of apoptosis by reducing CHEK2 activity could be protective-although not smoking would be far more so.

  5. Tracking Nonpalpable Breast Cancer for Breast-conserving Surgery With Carbon Nanoparticles

    PubMed Central

    Jiang, Yanyan; Lin, Nan; Huang, Sheng; Lin, Chongping; Jin, Na; Zhang, Zaizhong; Ke, Jun; Yu, Yinghao; Zhu, Jianping; Wang, Yu

    2015-01-01

    Abstract To examine the feasibility of using carbon nanoparticles to track nonpalpable breast cancer for breast-conserving surgery. During breast-conserving surgery, it is often very challenging to determine the boundary of tumor and identify involved lymph nodes. Currently used methods are useful in identifying tumor location, but do not provide direct visual guidance for resection margin during surgery. The study was approved by the Institutional Review Board of the Fuzhou General Hospital (Fuzhou, China). The current retrospective analysis included 16 patients with nonpalpable breast cancer receiving breast-conserving surgery under the guidance of preoperative marking using a carbon nanoparticle, as well as 3 patients receiving carbon nanoparticle marking followed by neoadjuvant treatment and then breast-conserving surgery. The Tumor Node Metastasis stage in the 16 cases included: T1N0M0 in 7, T1N1M0 in 2, T2N0M0 in 4, and T2N1M0 in the remaining 3 cases. The nanoparticle was injected at 12 sites at 0.5 cm away from the apparent edge under colored ultrasonography along 6 tracks separated by 60 degrees (2 sites every track). Lymph node status was also examined. The resection edge was free from cancer cells in all 16 cases (and the 3 cases with neoadjuvant treatment). Cancer cells were identified in majority of stained lymph nodes, but not in any of the unstained lymph nodes. No recurrence or metastasis was noticed after the surgery (2 to 22-month follow-up; median: 6 months). Tracking nonpalpable breast cancer with carbon nanoparticle could guide breast-conserving surgery. PMID:25761181

  6. Measurement of D0 Azimuthal Anisotropy at Midrapidity in Au +Au Collisions at √{sN N }=200 GeV

    NASA Astrophysics Data System (ADS)

    Adamczyk, L.; Adkins, J. K.; Agakishiev, G.; Aggarwal, M. M.; Ahammed, Z.; Ajitanand, N. N.; Alekseev, I.; Anderson, D. M.; Aoyama, R.; Aparin, A.; Arkhipkin, D.; Aschenauer, E. C.; Ashraf, M. U.; Attri, A.; Averichev, G. S.; Bai, X.; Bairathi, V.; Behera, A.; Bellwied, R.; Bhasin, A.; Bhati, A. K.; Bhattarai, P.; Bielcik, J.; Bielcikova, J.; Bland, L. C.; Bordyuzhin, I. G.; Bouchet, J.; Brandenburg, J. D.; Brandin, A. V.; Brown, D.; Bunzarov, I.; Butterworth, J.; Caines, H.; Calderón de la Barca Sánchez, M.; Campbell, J. M.; Cebra, D.; Chakaberia, I.; Chaloupka, P.; Chang, Z.; Chankova-Bunzarova, N.; Chatterjee, A.; Chattopadhyay, S.; Chen, X.; Chen, J. H.; Chen, X.; Cheng, J.; Cherney, M.; Christie, W.; Contin, G.; Crawford, H. J.; Das, S.; De Silva, L. C.; Debbe, R. R.; Dedovich, T. G.; Deng, J.; Derevschikov, A. A.; Didenko, L.; Dilks, C.; Dong, X.; Drachenberg, J. L.; Draper, J. E.; Dunkelberger, L. E.; Dunlop, J. C.; Efimov, L. G.; Elsey, N.; Engelage, J.; Eppley, G.; Esha, R.; Esumi, S.; Evdokimov, O.; Ewigleben, J.; Eyser, O.; Fatemi, R.; Fazio, S.; Federic, P.; Federicova, P.; Fedorisin, J.; Feng, Z.; Filip, P.; Finch, E.; Fisyak, Y.; Flores, C. E.; Fulek, L.; Gagliardi, C. A.; Garand, D.; Geurts, F.; Gibson, A.; Girard, M.; Greiner, L.; Grosnick, D.; Gunarathne, D. S.; Guo, Y.; Gupta, A.; Gupta, S.; Guryn, W.; Hamad, A. I.; Hamed, A.; Harlenderova, A.; Harris, J. W.; He, L.; Heppelmann, S.; Heppelmann, S.; Hirsch, A.; Hoffmann, G. W.; Horvat, S.; Huang, T.; Huang, B.; Huang, X.; Huang, H. Z.; Humanic, T. J.; Huo, P.; Igo, G.; Jacobs, W. W.; Jentsch, A.; Jia, J.; Jiang, K.; Jowzaee, S.; Judd, E. G.; Kabana, S.; Kalinkin, D.; Kang, K.; Kauder, K.; Ke, H. W.; Keane, D.; Kechechyan, A.; Khan, Z.; Kikoła, D. P.; Kisel, I.; Kisiel, A.; Kochenda, L.; Kocmanek, M.; Kollegger, T.; Kosarzewski, L. K.; Kraishan, A. F.; Kravtsov, P.; Krueger, K.; Kulathunga, N.; Kumar, L.; Kvapil, J.; Kwasizur, J. H.; Lacey, R.; Landgraf, J. M.; Landry, K. D.; Lauret, J.; Lebedev, A.; Lednicky, R.; Lee, J. H.; Li, X.; Li, C.; Li, W.; Li, Y.; Lidrych, J.; Lin, T.; Lisa, M. A.; Liu, H.; Liu, P.; Liu, Y.; Liu, F.; Ljubicic, T.; Llope, W. J.; Lomnitz, M.; Longacre, R. S.; Luo, S.; Luo, X.; Ma, G. L.; Ma, L.; Ma, Y. G.; Ma, R.; Magdy, N.; Majka, R.; Mallick, D.; Margetis, S.; Markert, C.; Matis, H. S.; Meehan, K.; Mei, J. C.; Miller, Z. W.; Minaev, N. G.; Mioduszewski, S.; Mishra, D.; Mizuno, S.; Mohanty, B.; Mondal, M. M.; Morozov, D. A.; Mustafa, M. K.; Nasim, Md.; Nayak, T. K.; Nelson, J. M.; Nie, M.; Nigmatkulov, G.; Niida, T.; Nogach, L. V.; Nonaka, T.; Nurushev, S. B.; Odyniec, G.; Ogawa, A.; Oh, K.; Okorokov, V. A.; Olvitt, D.; Page, B. S.; Pak, R.; Pandit, Y.; Panebratsev, Y.; Pawlik, B.; Pei, H.; Perkins, C.; Pile, P.; Pluta, J.; Poniatowska, K.; Porter, J.; Posik, M.; Poskanzer, A. M.; Pruthi, N. K.; Przybycien, M.; Putschke, J.; Qiu, H.; Quintero, A.; Ramachandran, S.; Ray, R. L.; Reed, R.; Rehbein, M. J.; Ritter, H. G.; Roberts, J. B.; Rogachevskiy, O. V.; Romero, J. L.; Roth, J. D.; Ruan, L.; Rusnak, J.; Rusnakova, O.; Sahoo, N. R.; Sahu, P. K.; Salur, S.; Sandweiss, J.; Saur, M.; Schambach, J.; Schmah, A. M.; Schmidke, W. B.; Schmitz, N.; Schweid, B. R.; Seger, J.; Sergeeva, M.; Seyboth, P.; Shah, N.; Shahaliev, E.; Shanmuganathan, P. V.; Shao, M.; Sharma, A.; Sharma, M. K.; Shen, W. Q.; Shi, Z.; Shi, S. S.; Shou, Q. Y.; Sichtermann, E. P.; Sikora, R.; Simko, M.; Singha, S.; Skoby, M. J.; Smirnov, N.; Smirnov, D.; Solyst, W.; Song, L.; Sorensen, P.; Spinka, H. M.; Srivastava, B.; Stanislaus, T. D. S.; Strikhanov, M.; Stringfellow, B.; Sugiura, T.; Sumbera, M.; Summa, B.; Sun, Y.; Sun, X. M.; Sun, X.; Surrow, B.; Svirida, D. N.; Szelezniak, M. A.; Tang, A. H.; Tang, Z.; Taranenko, A.; Tarnowsky, T.; Tawfik, A.; Thäder, J.; Thomas, J. H.; Timmins, A. R.; Tlusty, D.; Todoroki, T.; Tokarev, M.; Trentalange, S.; Tribble, R. E.; Tribedy, P.; Tripathy, S. K.; Trzeciak, B. A.; Tsai, O. D.; Ullrich, T.; Underwood, D. G.; Upsal, I.; Van Buren, G.; van Nieuwenhuizen, G.; Vasiliev, A. N.; Videbæk, F.; Vokal, S.; Voloshin, S. A.; Vossen, A.; Wang, G.; Wang, Y.; Wang, F.; Wang, Y.; Webb, J. C.; Webb, G.; Wen, L.; Westfall, G. D.; Wieman, H.; Wissink, S. W.; Witt, R.; Wu, Y.; Xiao, Z. G.; Xie, W.; Xie, G.; Xu, J.; Xu, N.; Xu, Q. H.; Xu, Y. F.; Xu, Z.; Yang, Y.; Yang, Q.; Yang, C.; Yang, S.; Ye, Z.; Ye, Z.; Yi, L.; Yip, K.; Yoo, I.-K.; Yu, N.; Zbroszczyk, H.; Zha, W.; Zhang, Z.; Zhang, X. P.; Zhang, J. B.; Zhang, S.; Zhang, J.; Zhang, Y.; Zhang, J.; Zhang, S.; Zhao, J.; Zhong, C.; Zhou, L.; Zhou, C.; Zhu, X.; Zhu, Z.; Zyzak, M.; STAR Collaboration

    2017-05-01

    We report the first measurement of the elliptic anisotropy (v2) of the charm meson D0 at midrapidity (|y |<1 ) in Au +Au collisions at √{sN N}=200 GeV . The measurement was conducted by the STAR experiment at RHIC utilizing a new high-resolution silicon tracker. The measured D0 v2 in 0%-80% centrality Au +Au collisions can be described by a viscous hydrodynamic calculation for a transverse momentum (pT) of less than 4 GeV /c . The D0 v2 as a function of transverse kinetic energy (mT-m0, where mT=√{pT2+m02 }) is consistent with that of light mesons in 10%-40% centrality Au +Au collisions. These results suggest that charm quarks have achieved local thermal equilibrium with the medium created in such collisions. Several theoretical models, with the temperature-dependent, dimensionless charm spatial diffusion coefficient (2 π T Ds) in the range of ˜2 - 12 , are able to simultaneously reproduce our D0 v2 result and our previously published results for the D0 nuclear modification factor.

  7. Effect of Medialization Thyroplasty on Glottic Airway Anatomy: Cadaver Model.

    PubMed

    Shinghal, Tulika; Anderson, Jennifer; Chung, Janet; Hong, Aaron; Bharatha, Aditya

    2016-11-01

    The purpose of this study was to investigate the change in airway dimensions after medialization thyroplasty (MT) using a cadaveric model. Helical computerized tomography (CT) was performed before and after placement of a silastic block in human larynges to investigate the effect on airway anatomy at the level of the glottis. Tissue density (TD) of the medialized vocal fold (VF) was documented to understand the effect on tissue displacement. This is a cadaveric study. Thirteen human cadaveric larynges underwent fine-cut CT scan before and after MT was performed using carved blocks in two sizes (small block and large block [LB]). Clientstream software was used to measure laryngeal dimensions: intraglottic volume (IGV), cross-sectional area (CSA), posterior-glottic diameter (PGD), VF density (in Hounsfield units [HUs]), and anterior-posterior diameter (APD). Eight sequential axial sections 0.625 mm cuts) at the level of the true VFs were analyzed. There was a significant decrease between the three conditions for IGV (P < 0.0001) and CSA (P < 0.0001). TD of the VF was increased after MT as indicated by HU increase (P = 0.0003). APD was not significantly changed. PGD was significantly different between the no block to LB placement (P = 0.0012). MT significantly changes the IGV and CSA at the level of the glottis. Density in the true VF was significantly increased. These findings have important implications for understanding volumetric effects of MT. Copyright © 2015 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  8. HIF-1α P582S and A588T polymorphisms and digestive system cancer risk-a meta-analysis.

    PubMed

    Yang, Xi; Zhang, Chi; Zhu, Hong-Cheng; Qin, Qin; Zhao, Lian-Jun; Liu, Jia; Xu, Li-Ping; Zhang, Qu; Cai, Jing; Ma, Jian-Xin; Cheng, Hong-Yan; Sun, Xin-Chen

    2014-03-01

    Hypoxia-inducible factor-1 (HIF-1) influences cancer progression and metastasis through various mechanisms, and HIF-1α polymorphisms are reportedly associated with many cancers; however, the associations of HIF-1α P582S and A588T polymorphisms with the risk of digestive system cancer remain inconclusive. To understand the role of HIF-1α P582S and A588T genotypes in digestive cancer development, we conducted a comprehensive meta-analysis involving 1,517 cases and 3,740 controls. Overall, the P582S polymorphism was not significantly associated with digestive system cancers in all genotypes. By contrast, the A588T polymorphism was significantly associated with digestive system cancers in the dominant model (TT/AT vs. AA: OR = 3.17, 95% CI: 1.21, 8.25; P heterogeneity < 0.001). In subgroup analysis for cancer types, the two polymorphisms were only associated with increased risk of pancreatic cancer (P582S: SS vs. PP: OR = 2.51, 95% CI: 1.31, 4.81; SS vs. OR = 8.73, 95% CI: 1.33, 57.1; A588T: TT vs. AA: OR = 9.30, 95% CI: 1.12, 77.6; P heterogeneity = 0.478; TT vs. OR = 3.14, 95% CI: 1.99, 4.97; P heterogeneity = 0.098; TT/AT vs. AA: OR = 8.65, 95% CI: 1.05, 71.6; P heterogeneity = 0.418). According to the source of ethnicity, the P582S and the A588T polymorphisms are both significantly associated with an increased risk of cancer among Caucasians in the homozygote model (SS vs. PP: OR = 2.41, 95% CI: 1.24, 4.691; P heterogeneity = 0.010; TT vs. AA: OR = 98.6, 95% CI: 4.37, 2,224; P heterogeneity = 0.040) and the recessive model (SS vs. OR = 9.48, 95% CI: 1.12, 80.3; P heterogeneity < 0.001; TT vs. OR = 82.7, 95% CI: 3.79, 1,802; P heterogeneity = 0.041). Our findings suggest that the HIF-1α A588T polymorphism is significantly associated with higher cancer risk and the P582S polymorphism is significantly associated with pancreatic cancer risk. Furthermore, the effect of both polymorphisms on

  9. The role of Her2-Nrf2 axis in induction of oxaliplatin resistance in colon cancer cells.

    PubMed

    Pirpour Tazehkand, Abbas; Akbarzadeh, Maryam; Velaie, Kobra; Sadeghi, Mohammad Reza; Samadi, Nasser

    2018-04-20

    Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a pivotal role in promoting chemoresistance by regulation of antioxidants and detoxification enzymes. Her2 is a member of tyrosine kinase receptor family with a key function in resistance of cancer cells to chemotherapeutics. The aim of this study was to investigate the possible cross talk between Nrf2 and Her2 mediated signaling pathways in development of oxaliplatin resistance in colon cancer cells. We first generated oxaliplatin-resistant LS174T and SW480 colon cancer cells with different Her2 expression levels by employing IC50 concentrations followed by a resting period. We evaluated the viability and apoptosis of the cells by MTT and flow cytometry assays, respectively. Nrf2 and Her2 gene expression levels were examined by qRT-PCR. The morphology analysis and combination index calculation were performed using the ImagJ and CompuSyn softwares, respectively. Development of resistant cells revealed a marked increase in half maximal inhibitory concentration (IC50) value from 3.95 ± 0.92 μM to 29.27 ± 3.13 μM in SW480 cells and 377 ± 46 nM to 9.59 ± 0.76 μM in LS174T cells with a significant change in morphology of the cells from elongated to small round shape (p < 0.05). Her2 expression level was increased in both types of resistant cells, but the Nrf2 expression was increased in LS174T resistant (LS174T/Res) cells and decreased in SW480/Res cells which were consistent with the level of resistance in these cells (25 fold increase in IC50 value in LS174T/Res cells versus 7 fold increase in this value in SW480/Res cells). Inhibition of either Nrf2 or Her2 alone and in combination caused a significant increase in oxaliplatin-induced cytotoxicity and apoptosis with maximum effects in SW480/Res cells with low Her2 and Nrf2 expression levels. Altogether, our results suggest that inhibition of Nrf2 signaling in colon cancer patients with Her2 overexpression can be considered as

  10. Recommendations for pathologic staging (pTNM) of cancer of the esophagus and esophagogastric junction for the 8th edition AJCC/UICC staging manuals.

    PubMed

    Rice, T W; Ishwaran, H; Hofstetter, W L; Kelsen, D P; Apperson-Hansen, C; Blackstone, E H

    2016-11-01

    We report analytic and consensus processes that produced recommendations for pathologic stage groups (pTNM) of esophageal and esophagogastric junction cancer for the AJCC/UICC cancer staging manuals, 8th edition. The Worldwide Esophageal Cancer Collaboration provided data for 22,654 patients with epithelial esophageal cancers; 13,300 without preoperative therapy had pathologic assessment after esophagectomy or endoscopic treatment. Risk-adjusted survival for each patient was developed using random survival forest analysis to identify data-driven pathologic stage groups wherein survival decreased monotonically with increasing group, was distinctive between groups, and homogeneous within groups. The AJCC Upper GI Task Force, by smoothing, simplifying, expanding, and assessing clinical applicability, produced consensus pathologic stage groups. For pT1-3N0M0 squamous cell carcinoma (SCC) and pT1-2N0M0 adenocarcinoma, pT was inadequate for grouping; subcategorizing pT1 and adding histologic grade enhanced staging; cancer location improved SCC staging. Consensus eliminated location for pT2N0M0 and pT3N0M0G1 SCC groups, and despite similar survival, restricted stage 0 to pTis, excluding pT1aN0M0G1. Metastases markedly reduced survival; pT, pN, and pM sufficiently grouped advanced cancers. Stage IIA and IIB had different compositions for SCC and adenocarcinoma, but similar survival. Consensus stage IV subgrouping acknowledged pT4N+ and pN3 cancers had poor survival, similar to pM1. Anatomic pathologic stage grouping, based on pTNM only, produced identical consensus stage groups for SCC and adenocarcinoma at the cost of homogeneity in early groups. Pathologic staging can neither direct pre-treatment decisions nor aid in prognostication for treatment other than esophagectomy or endoscopic therapy. However, it provides a clean, single therapy reference point for esophageal cancer. © 2016 International Society for Diseases of the Esophagus.

  11. A hybrid of B and T lymphoblastic cell line could potentially substitute dendritic cells to efficiently expand out Her-2/neu-specific cytotoxic T lymphocytes from advanced breast cancer patients in vitro.

    PubMed

    Chen, Sheng; Gu, Feifei; Li, Kang; Zhang, Kai; Liu, Yangyang; Liang, Jinyan; Gao, Wei; Wu, Gang; Liu, Li

    2017-02-28

    Adoptive transfer of cytotoxic T lymphocytes (CTLs) holds promises to cure cancer. However, this treatment is hindered by lacking a robust way to specifically expand out CTLs. Here, we developed a hybrid of B lymphoblastic cell line and T lymphoblastic cell line (T2 cells) as a substitute of dendritic cells, together with irradiated autologous peripheral blood mononuclear cell (PBMC) as feeder cells and rhIL-2, to activate and expand Her-2/neu-specific CD8 + T cells from human epidermal growth factor receptor 2 (Her-2/neu) and human leukocyte antigen (HLA)-A2 double positive advanced breast cancer patients in vitro. These Her-2/neu-loaded T2 cells reproducibly activated and expanded out Her-2/neu-specific CD8 + T cells to 10 7 in 8 weeks. Furthermore, these Her-2/neu-specific CD8 + T cells had good sensitivity of recognition and killing Her-2/neu-overexpressed breast cancer cell line SK.BR.3. This technique gives us another insight on how to rapidly obtain sufficient CTLs for adoptive cancer immunotherapy.

  12. Evaluation of blood T-lymphocyte subpopulations involved in host cellular immunity in dogs with mammary cancer.

    PubMed

    Karayannopoulou, Maria; Anagnostou, Tilemachos; Margariti, Apostolia; Kostakis, Charalampos; Kritsepi-Konstantinou, Maria; Psalla, Dimitra; Savvas, Ioannis

    2017-04-01

    Cancer-bearing patients are often immunosuppressed. In dogs with mammary or other cancers, various alterations in blood cell populations involved in host cellular immunity have been reported; among these cell populations some T-lymphocyte subsets play an important role against cancer. The purpose of the present study was to investigate any alterations in circulating T-lymphocyte subpopulations involved in cellular immunity in bitches with mammary cancer, in comparison to age-matched healthy intact bitches. Twenty eight dogs with mammary cancer and 14 control dogs were included in this study. Twelve out of the 28 bitches had mammary cancer of clinical stage II and 16/28 of stage III. Histological examination revealed that 23/28 animals had carcinomas, 3/28 sarcomas and 2/28 carcinosarcomas. White blood cell, neutrophil and lymphocyte absolute numbers were measured by complete blood count. Furthermore, blood T-lymphocyte population (CD3 + ) and the subpopulations CD4 + , CD8 + and CD5 low+ were assessed by flow cytometry. White blood cell and neutrophil but not lymphocyte absolute numbers were higher (P=0.003 and P=0.001, respectively) in cancer patients than controls. Flow cytometric analysis revealed that the relative percentage of T-lymphocytes (CD3 + ) and of CD4 + , CD8 + subpopulations was lower (the CD4 + /CD8 + ratio was higher), whereas the percentage of CD5 low+ T-cells was higher, in dogs with cancer compared to controls; however, a statistically significant difference was found only in the case of CD8 + T-cells (P=0.014), whereas in the case of the CD4 + /CD8 + ratio the difference almost reached statistical significance (P=0.059). Based on these findings, it can be suggested that, although the absolute number of blood lymphocytes is unchanged, the relative percentages of T-lymphocyte subpopulations involved in host cell-mediated immunity are altered, but only cytotoxic CD8 + T-cells are significantly suppressed, in dogs with mammary cancer of clinical

  13. Myelin water and T(2) relaxation measurements in the healthy cervical spinal cord at 3.0T: repeatability and changes with age.

    PubMed

    MacMillan, Erin L; Mädler, Burkhard; Fichtner, Nicole; Dvorak, Marcel F; Li, David K B; Curt, Armin; MacKay, Alex L

    2011-01-15

    Multiecho T(2) relaxation measurements offer specific information about myelin content through the myelin water fraction (MWF), as well as about the water environments through the intra- and extra-cellular (IE), and global, geometric mean T(2) (GMT(2)) times. While these measurements have yielded new insights into brain development and pathologies, they have yet to be thoroughly investigated in the spinal cord. The goals of this study were: (1) to apply a new 3D multiecho T(2) relaxation measurement in the cervical spine with sufficient axial resolution to distinguish grey and white matter; (2) to perform a pilot reliability assessment of the resulting MWF and GMT(2) measures in a target population; and (3) to detect differences in these measures between a younger cohort (20-30 years of age) and an older cohort (50-75 years of age) of healthy adults. The results demonstrated that the MWF in younger healthy adults follows the known pattern of lower myelin content in grey matter (mean (95% confidence interval)) (0.049 (0.030-0.067)) as compared to white matter (0.296 (0.275-0.317), p<0.001). The reliability coefficients were 0.65 and 0.82 for the MWF in the dorsal (DC) and lateral column (LC) white matter, respectively; 0.79 and 0.52 for the IE GMT(2); and 0.74 and 0.73 for the global GMT(2). Significantly lower MWF were found in the older adults than in the younger adults (DC p=0.014; LC p=0.012), as well as lower IE GMT(2) times (DC p=0.008; LC p=0.042), however, the global GMT(2) times did not show any differences. These changes in MWF and IE GMT(2) times, but not in global GMT(2) times, indicate that multiecho T(2) relaxation measures are sensitive to changes in myelin integrity and cell morphology that may not be apparent on conventional T(2) weighted images. Copyright © 2010 Elsevier Inc. All rights reserved.

  14. Spin reorientation and magnetoelastic properties of ferromagnetic T b1 -xN dxC o2 systems with a morphotropic phase boundary

    NASA Astrophysics Data System (ADS)

    Murtaza, Adil; Yang, Sen; Chang, Tieyan; Ghani, Awais; Khan, Muhammad Tahir; Zhang, Rui; Zhou, Chao; Song, Xiaoping; Suchomel, Matthew; Ren, Yang

    2018-03-01

    The spin reorientation (SR) and magnetoelastic properties of pseudobinary ferromagnetic T b1 -xN dxC o2 (0 ≤x ≤1.0 ) systems involving a morphotropic phase boundary (MPB) were studied by high-resolution synchrotron x-ray diffraction (XRD), magnetization, and magnetostriction measurements. The easy magnetization direction of the Laves phase lies along the 〈111 〉 axis with x <0.65 , whereas it lies along the 〈100 〉 axis for x >0.65 below Curie temperature (TC). The temperature-dependent magnetization curves showed SR; this can be explained by a two-sublattice model. Based on the synchrotron (XRD) and magnetization measurements, the SR phase diagram for a MPB composition of T b0.35N d0.65C o2 was obtained. Contrary to previously reported ferromagnetic systems involving MPB, the MPB composition of T b0.35N d0.65C o2 exhibits a low saturation magnetization (MS), indicating a compensation of the Tb and Nd magnetic moments at MPB. The anisotropic magnetostriction (λS) first decreased until x =0.8 and then continuously increased in the negative direction with further increase of Nd concentration. The decrease in magnetostriction can be attributed to the decrease of spontaneous magnetostriction λ111 and increase of λ100 with opposite sign to λ111. This paper indicates an anomalous type of MPB in the ferromagnetic T b1 -xN dxC o2 system and provides an active way to design novel functional materials with exotic properties.

  15. SU-E-P-33: Critical Role of T2-Weighted Imaging Combined with Diffusion-Weighted Imaging of MRI in Diagnosis of Loco-Regional Recurrent Esophageal Cancer After Radical Surgery

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Deng, G; Qiao, L; Liang, N

    Purpose: We perform this study to investigate the diagnostic efficacy of T2-weighted MRI (T2WI) and diffusion-weighted MRI (DWI) in confirming local relapses of esophageal cancer in patients highly suspected of recurrence after eradicating surgery. Methods: Forty-two postoperative esophageal cancer patients with clinical suspicions of cancer recurrence underwent 3.0T MRI applying axial, coronal, sagittal T2WI and axial DWI sequences. Two experienced radiologists (R1 and R2) both used two methods (T2WI, T2WI+DWI) to observe the images, and graded the patients ranging from 1 to 5 to represent severity of the disease based on visual signal intensity (patients equal to or more thanmore » grade 3 was confirmed as recurrent disease) Results: 27/42patients were verified of recurrent disease by pathologic findings and/or imaging findings during follow-up. The sensitivity, specificity and accuracy of R1 applying T2WI+DWI are 96%, 87% and 93% versus 81%, 80% and 77% on T2WI, these figures by R2 were 96%, 93% and 95% versus 89%, 93% and 90%. The receiver operating curve (ROC) analyses suggest that both of the two readers can obtain better accuracy when adding DWI to T2WI compared with T2WI alone. Kappa test between R1 and R2 indicates excellent inter-observer agreement on T2WI+DWI. Conclusion: Standard T2WI in combination DWI can achieve better accuracy than T2WI alone in diagnosing local recurrence of esophageal cancer, and improve consistency between different readers.« less

  16. T staging of gastric cancer: role of multi-detector row CT.

    PubMed

    Kumano, Seishi; Murakami, Takamichi; Kim, Tonsok; Hori, Masatoshi; Iannaccone, Riccardo; Nakata, Saki; Onishi, Hiromitsu; Osuga, Keigo; Tomoda, Kaname; Catalano, Carlo; Nakamura, Hironobu

    2005-12-01

    To evaluate retrospectively the accuracy of multi-detector row computed tomography (CT) in the assessment of serosal invasion in patients with gastric cancer. The Ethics Committee does not require approval or informed consent for retrospective studies. Forty-one consecutive patients (24 men, 17 women; mean age, 68 years) with gastric cancer were included in this study. All patients were given 600 mL of tap water to drink and were positioned prone or supine on the scanning table. The detector row configuration included four detector rows, a section thickness of 1.25 mm, a pitch of 6, and a reconstruction interval of 0.63 mm. Transverse and multiplanar reconstruction images were simultaneously evaluated by two independent observers to assess the depth of tumor invasion in the gastric wall (ie, T stage). T staging at multi-detector row CT was compared with T staging at histologic evaluation (reference standard), which was performed by means of surgical or histologic examination of the resected specimen. We also calculated the sensitivity, specificity, and accuracy of multi-detector row CT for each observer in the assessment of serosal invasion. Analysis of interobserver agreement showed substantial or almost perfect agreement (nonweighted kappa value of 0.78 and weighted kappa value of 0.85). Correct assessment of gastric wall invasion was 80% and 85% for observers 1 and 2, respectively. The sensitivity, specificity, and accuracy of multi-detector row CT in the assessment of serosal invasion were 90%, 95%, and 93%, respectively, for observer 1 and 80%, 97%, and 93%, respectively, for observer 2. Overstaging occurred in six patients, and understaging occurred in five patients. All understaged tumors were scirrhous subtype gastric cancer. Multi-detector row CT scanning of patients with gastric cancer gave 93% accuracy in the assessment of serosal invasion in patients with gastric cancer. RSNA, 2005

  17. Adoptive transfer of ex vivo expanded Vγ9Vδ2 T cells in combination with zoledronic acid inhibits cancer growth and limits osteolysis in a murine model of osteolytic breast cancer.

    PubMed

    Zysk, Aneta; DeNichilo, Mark O; Panagopoulos, Vasilios; Zinonos, Irene; Liapis, Vasilios; Hay, Shelley; Ingman, Wendy; Ponomarev, Vladimir; Atkins, Gerald; Findlay, David; Zannettino, Andrew; Evdokiou, Andreas

    2017-02-01

    Bone metastases occur in over 75% of patients with advanced breast cancer and are responsible for high levels of morbidity and mortality. In this study, ex vivo expanded cytotoxic Vγ9Vδ2 T cells isolated from human peripheral blood were tested for their anti-cancer efficacy in combination with zoledronic acid (ZOL), using a mouse model of osteolytic breast cancer. In vitro, expanded Vγ9Vδ2 T cells were cytotoxic against a panel of human breast cancer cell lines, and ZOL pre-treatment further sensitised breast cancer cells to killing by Vγ9Vδ2 T cells. Vγ9Vδ2 T cells adoptively transferred into NOD/SCID mice localised to osteolytic breast cancer lesions in the bone, and multiple infusions of Vγ9Vδ2 T cells reduced tumour growth in the bone. ZOL pre-treatment potentiated the anti-cancer efficacy of Vγ9Vδ2 T cells, with mice showing further reductions in tumour burden. Mice treated with the combination also had reduced tumour burden of secondary pulmonary metastases, and decreased bone degradation. Our data suggests that adoptive transfer of Vγ9Vδ2 T cell in combination with ZOL may prove an effective immunotherapeutic approach for the treatment of breast cancer bone metastases. Copyright © 2016. Published by Elsevier Ireland Ltd.

  18. Microstructure and thermal stability of Cu/Zr0.3Al0.7N/Zr0.2Al0.8N/Al34O60N6 cermet-based solar selective absorbing coatings

    NASA Astrophysics Data System (ADS)

    Meng, Jian-ping; Guo, Rui-rui; Li, Hu; Zhao, Lu-ming; Liu, Xiao-peng; Li, Zhou

    2018-05-01

    Solar selective absorbing coatings play a valuable role in photo-thermal conversion for high efficiency concentrating solar power systems (CSP). In this paper, a novel Cu/Zr0.3Al0.7N/Zr0.2Al0.8N/Al34O60N6 cermet-based solar selective absorbing coating was successfully deposited by ion beam assisted deposition. The optical properties, microstructure and element distribution in depth were investigated by spectroscopic ellipsometry, UV-vis-NIR spectrophotometer, transmission electron microscope (TEM) and Auger electron spectroscopy (AES), respectively. A high absorptance of 0.953 and a low thermal emittance of 0.079 at 400 °C are obtained by the integral computation according to the whole reflectance from 300 nm to 28,800 nm. After annealing treatment at 400 °C (in vacuum) for 192 h, the deposited coating exhibits the high thermal stability. Whereas, the photothermal conversion efficiency decreases from 12.10 to 6.86 due to the emittance increase after annealing at 600 °C for 192 h. Meanwhile, the nitrogen atom in the Zr0.3Al0.7N sub-layer diffuses toward the adjacent sub-layer due to the spinodal decomposition of metastable c-ZrAlN and the phase transition from c-AlN to h-AlN, which leads to the composition of the Zr0.3Al0.7N sub-layer deviates the initial design. This phenomenon has a guide effect for the thermal-stability improvement of cermet coatings. Additionally, a serious diffusion between copper and silicon substrate also contributes to the emittance increase.

  19. Surgical Management of Lung Cancer Involving the Chest Wall.

    PubMed

    Lanuti, Michael

    2017-05-01

    The prevalence of chest wall invasion by non-small cell lung cancer is < 10% in published surgical series. The role of radiation or chemotherapy around the complete resection of lung cancer invading the chest wall, excluding the superior sulcus of the chest, is poorly defined. Survival of patients with lung cancer invading the chest wall is dependent on lymph node involvement and completeness of en-bloc resection. In some patients harboring T3N0 disease, 5-year survival in excess of 50% can be achieved. Offering en-bloc resection of lung cancer invading chest wall to patients with T3N1 or T3N2 disease is controversial. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. High p95HER2/HER2 Ratio Associated With Poor Outcome in Trastuzumab-Treated HER2-Positive Metastatic Breast Cancer NCCTG N0337 and NCCTG 98-32-52 (Alliance).

    PubMed

    Chumsri, Saranya; Sperinde, Jeff; Liu, Heshan; Gligorov, Joseph; Spano, Jean-Philippe; Antoine, Martine; Moreno Aspitia, Alvaro; Tan, Winston; Winslow, John; Petropoulos, Christos J; Chenna, Ahmed; Bates, Michael; Weidler, Jodi Marie; Huang, Weidong; Dueck, Amylou; Perez, Edith A

    2018-03-12

    Purpose: p95HER2 is a truncated form of HER2 that confers resistance to trastuzumab in vitro , but clinical results have been conflicting to date. Given that p95HER2 levels correlate with total HER2 expression levels, which confer better outcomes, we sought to evaluate the p95HER2/HER2 ratio in the North Central Cancer Treatment Group N0337 and N98-32-52 trials. Experimental Design: The HERmark assay and VeraTag technology (Monogram Biosciences) were used to measure total HER2 and p95HER2 expression levels in 91 patient samples. Results: In the multivariate model, increasing total HER2 level was significantly associated with longer (OS; HR, 0.33; P = 0.002) and decreasing p95HER2 level was significantly associated with longer OS (HR, 4.2; P = 0.01). Total HER2 expression level was significantly associated with longer progression-free survival (PFS) (HR, 0.57; P = 0.04), whereas p95HER2 level was not (HR, 1.7; P = 0.25). However, there was a positive association between p95HER2 and total HER2 expression levels ( R 2 = 0.48; P < 0.001). Consistent with our hypothesis, the ratio of p95HER2/HER2 was significantly associated with worsening PFS (HR, 1.7; P = 0.04) and OS (HR, 2.8; P = 0.002). Patients with the highest tertile of p95HER2/HER2 values had significantly less favorable PFS (HR, 1.8; P = 0.06) and OS (HR, 2.3; P = 0.02). Conclusions: A high p95HER2/HER2 ratio identified patients with metastatic breast cancer with poor outcomes on trastuzumab-based therapies. Further investigation of the p95HER2/HER2 ratio as a potential prognostic or predictive biomarker for HER2-targeted therapy is warranted. Clin Cancer Res; 1-6. ©2018 AACR. ©2018 American Association for Cancer Research.

  1. Two-dimensional wide-band-gap nitride semiconductors: Single-layer 1 T -X N2 (X =S ,Se , and Te )

    NASA Astrophysics Data System (ADS)

    Lin, Jia-He; Zhang, Hong; Cheng, Xin-Lu; Miyamoto, Yoshiyuki

    2016-11-01

    Recently, the two-dimensional (2D) semiconductors arsenene and antimonene, with band gaps larger than 2.0 eV, have attracted tremendous interest, especially for potential applications in optoelectronic devices with a photoresponse in the blue and UV range. Motivated by this exciting discovery, types of highly stable wide-band-gap 2D nitride semiconductors were theoretically designed. We propose single-layer 1 T -X N2 (X =S , Se, and Te) via first-principles simulations. We compute 1 T -X N2 (X =S , Se, and Te) with indirect band gaps of 2.825, 2.351, and 2.336 eV, respectively. By applying biaxial strain, they are able to induce the transition from a wide-band-gap semiconductor to a metal, and the range of absorption spectra of 1 T -X N2 (X =S , Se, and Te) obviously extend from the ultraviolet region to the blue-purple light region. With an underlying graphene, we find that 1 T -X N2 can completely shield the light absorption of graphene in the range of 1-1.6 eV. Our research paves the way for optoelectronic devices working under blue or UV light, and mechanical sensors based on these 2D crystals.

  2. Esophageal carcinoma: Ex vivo evaluation by high-spatial-resolution T2 -mapping MRI compared with histopathological findings at 3.0T.

    PubMed

    Wei, Yi; Wu, Sen; Gao, Feifei; Sun, Tingyi; Zheng, Dandan; Ning, Peigang; Zhao, Cuihua; Li, Ziyuan; Li, Xiaodong; Li, Linlin; Zhu, Shaocheng

    2017-06-01

    To prospectively determine the feasibility of T 2 -mapping magnetic resonance imaging (MRI) to quantitatively describe the signal characteristics of the normal esophageal wall and assess the depth of esophageal wall invasion by carcinoma at 3.0T. Thirty-two patient specimens, each having foci of carcinoma, were studied using 3.0T MR. Freehand regions of interest were placed to measure the T 2 value of the normal esophageal layers and were compared with the regions of carcinoma. Three independent readers reviewed the MR images to evaluate the depth of carcinoma invasion; when the three radiologists could not fully agree with each other, the final stage was determined by consensus. The Games-Howell test was used to compare the difference between the normal esophageal layers and carcinoma. Spearman correlation coefficient analysis was used to compare the stage at MRI with that at histopathological analysis. The interobserver agreement was compared with Cohen's kappa. The sensitivity, specificity, and accuracy for detecting carcinoma invasion were calculated. The T 2 values between the carcinoma and normal esophageal layers were different (all P < 0.01), except for the inner circular muscle (P = 0.511). The T 2 value of each layer of the normal esophageal wall was also different from that of the adjacent layer (all P < 0.01). In 29 of 32 lesions, the depth of the esophageal wall invasion determined by MR was consistent with the histopathological stage (r = 0.969, P < 0.001). The sensitivity, specificity, and accuracy were 80%, 96.3%, and 93.8%, respectively, for invasion into the mucosa; 77.8%, 95.7%, and 90.6%, respectively, for invasion into submucosa; 100%, 95.8%, and 96.9%, respectively, for invasion into muscularis propria; and 100%, 100%, and 100%, respectively, for invasion into the adventitia. T 2 -mapping MR images obtained using a 3.0T MR scanner can be used to depict the precise histopathological layers of the esophageal wall clearly and provide

  3. Exact deconstruction of the 6D (2,0) theory

    NASA Astrophysics Data System (ADS)

    Hayling, J.; Papageorgakis, C.; Pomoni, E.; Rodríguez-Gómez, D.

    2017-06-01

    The dimensional-deconstruction prescription of Arkani-Hamed, Cohen, Kaplan, Karch and Motl provides a mechanism for recovering the A-type (2,0) theories on T 2, starting from a four-dimensional N=2 circular-quiver theory. We put this conjecture to the test using two exact-counting arguments: in the decompactification limit, we compare the Higgs-branch Hilbert series of the 4D N=2 quiver to the "half-BPS" limit of the (2,0) superconformal index. We also compare the full partition function for the 4D quiver on S 4 to the (2,0) partition function on S 4 × T 2. In both cases we find exact agreement. The partition function calculation sets up a dictionary between exact results in 4D and 6D.

  4. IDEAL 3D spoiled gradient echo of the articular cartilage of the knee on 3.0 T MRI: a comparison with conventional 3.0 T fast spin-echo T2 fat saturation image.

    PubMed

    Han, Chul Hee; Park, Hee Jin; Lee, So Yeon; Chung, Eun Chul; Choi, Seon Hyeong; Yun, Ji Sup; Rho, Myung Ho

    2015-12-01

    Many two-dimensional (2D) morphologic cartilage imaging sequences have disadvantages such as long acquisition time, inadequate spatial resolution, suboptimal tissue contrast, and image degradation secondary to artifacts. IDEAL imaging can overcome these disadvantages. To compare sound-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and quality of two different methods of imaging that include IDEAL 3D SPGR and 3.0-T FSE T2 fat saturation (FS) imaging and to evaluate the utility of IDEAL 3D SPGR for knee joint imaging. SNR and CNR of the patellar and femoral cartilages were measured and calculated. Two radiologists performed subjective scoring of all images for three measures: general image quality, FS, and cartilage evaluation. SNR and CNR values were compared by paired Student's t-tests. Mean SNRs of patellar and femoral cartilages were 90% and 66% higher, respectively, for IDEAL 3D SPGR. CNRs of patellar cartilages and joint fluids were 2.4 times higher for FSE T2 FS, and CNR between the femoral cartilage and joint fluid was 2.2 times higher for FSE T2 FS. General image quality and FS were superior using FSE T2 FS compared to those of IDEAL 3D SPGR imaging according to both readers, while cartilage evaluation was superior using IDEAL 3D SPGR. Additionally, cartilage injuries were more prominent in IDEAL 3D SPGR than in FSE T2FS according to both readers. IDEAL 3D SPGR images show excellent visualization of patellar and femoral cartilages in 3.0 T and can compensate for the weaknesses of FSE T2 FS in the evaluation of cartilage injuries. © The Foundation Acta Radiologica 2014.

  5. [Expression of molecular markers detected by immunohistochemistry and risk of lymph node metastasis in stage T1 and T2 colorecrectal cancers].

    PubMed

    Wang, Fu-long; Wan, De-sen; Lu, Zhen-hai; Fang, Yu-jing; Li, Li-ren; Chen, Gong; Wu, Xiao-jun; Ding, Pei-rong; Kong, Ling-heng; Lin, Jun-zhong; Pan, Zhi-zhong

    2013-04-01

    To study the molecular risk factors of lymph node metastasis in stage T1 and T2 colorectal cancers by tissue microarray and immunohistochemistry techniques. Two hundred and three patients with stage T1 and T2 colorectal carcinoma who underwent radical surgery from 1999 to 2010 in our department were included in this study. Their clinicopathological data were retrospectively analyzed. Expression of the following 14 molecular markers were selected and assayed by tissue microarray and immunohistochemistry: VEGFR-3, HER2, CD44v6, CXCR4, TIMP-1, EGFR, IGF-1R, IGF-2, IGFBP-1, ECAD, MMP-9, RKIP, CD133, MSI. Chi-squared test and logistic regression were used to evaluate the variables as potential risk factors for lymph node metastasis. The positive expression rates of biomarkers were as following: VEGFR-3 (44.3%), EGFR (30.5%), HER-2 (28.1%), IGF-1R (63.5%), IGF-2 (44.8%), IGFBP-1 (70.9%), ECAD (45.8%), CD44v6 (51.2%), MMP-9 (44.3%), TIMP-1 (41.4%), RKIP (45.3%), CXCR4 (40.9%), and CD133 (49.8%). The positive rate of MSI expression was 22.2%. Both univariate and multivariate analyses showed that VEGFR-3, HER-2, and TIMP-1 were significant predictors of lymph node metastasis. Univariate analysis showed that CD44v6 and CXCR4 were significant significant predictors of lymph node metastasis. VEGFR-3, HER2 and TIMP-1 are independent factors for lymph node metastasis in stage T1 and T2 colorectal cancers.

  6. The immediate effect of long-distance running on T2 and T2* relaxation times of articular cartilage of the knee in young healthy adults at 3.0 T MR imaging

    PubMed Central

    Welsch, Goetz H; Laqmani, Azien; Henes, Frank O; Kaul, Michael G; Schoen, Gerhard; Adam, Gerhard; Regier, Marc

    2016-01-01

    Objective: To quantitatively assess the immediate effect of long-distance running on T2 and T2* relaxation times of the articular cartilage of the knee at 3.0T in young healthy adults. Methods: 30 healthy male adults (18–31 years) who perform sports at an amateur level underwent an initial MRI at 3.0T with T2 weighted [16 echo times (TEs): 9.7–154.6 ms] and T2* weighted (24 TEs: 4.6–53.6 ms) relaxation measurements. Thereafter, all participants performed a 45-min run. After the run, all individuals were immediately re-examined. Data sets were post-processed using dedicated software (ImageJ; National Institute of Health, Bethesda, MD). 22 regions of interest were manually drawn in segmented areas of the femoral, tibial and patellar cartilage. For statistical evaluation, Pearson product–moment correlation coefficients and confidence intervals were computed. Results: Mean initial values were 35.7 ms for T2 and 25.1 ms for T2*. After the run, a significant decrease in the mean T2 and T2* relaxation times was observed for all segments in all participants. A mean decrease of relaxation time was observed for T2 with 4.6 ms (±3.6 ms) and for T2* with 3.6 ms (±5.1 ms) after running. Conclusion: A significant decrease could be observed in all cartilage segments for both biomarkers. Both quantitative techniques, T2 and T2*, seem to be valuable parameters in the evaluation of immediate changes in the cartilage ultrastructure after running. Advances in knowledge: This is the first direct comparison of immediate changes in T2 and T2* relaxation times after running in healthy adults. PMID:27336705

  7. The immediate effect of long-distance running on T2 and T2* relaxation times of articular cartilage of the knee in young healthy adults at 3.0 T MR imaging.

    PubMed

    Behzadi, Cyrus; Welsch, Goetz H; Laqmani, Azien; Henes, Frank O; Kaul, Michael G; Schoen, Gerhard; Adam, Gerhard; Regier, Marc

    2016-08-01

    To quantitatively assess the immediate effect of long-distance running on T2 and T2* relaxation times of the articular cartilage of the knee at 3.0T in young healthy adults. 30 healthy male adults (18-31 years) who perform sports at an amateur level underwent an initial MRI at 3.0T with T2 weighted [16 echo times (TEs): 9.7-154.6 ms] and T2* weighted (24 TEs: 4.6-53.6 ms) relaxation measurements. Thereafter, all participants performed a 45-min run. After the run, all individuals were immediately re-examined. Data sets were post-processed using dedicated software (ImageJ; National Institute of Health, Bethesda, MD). 22 regions of interest were manually drawn in segmented areas of the femoral, tibial and patellar cartilage. For statistical evaluation, Pearson product-moment correlation coefficients and confidence intervals were computed. Mean initial values were 35.7 ms for T2 and 25.1 ms for T2*. After the run, a significant decrease in the mean T2 and T2* relaxation times was observed for all segments in all participants. A mean decrease of relaxation time was observed for T2 with 4.6 ms (±3.6 ms) and for T2* with 3.6 ms (±5.1 ms) after running. A significant decrease could be observed in all cartilage segments for both biomarkers. Both quantitative techniques, T2 and T2*, seem to be valuable parameters in the evaluation of immediate changes in the cartilage ultrastructure after running. This is the first direct comparison of immediate changes in T2 and T2* relaxation times after running in healthy adults.

  8. MR elastography to measure the effects of cancer and pathology fixation on prostate biomechanics, and comparison with T 1, T 2 and ADC

    NASA Astrophysics Data System (ADS)

    McGrath, Deirdre M.; Lee, Jenny; Foltz, Warren D.; Samavati, Navid; van der Kwast, Theo; Jewett, Michael A. S.; Chung, Peter; Ménard, Cynthia; Brock, Kristy K.

    2017-02-01

    MRI is under evaluation for image-guided intervention for prostate cancer. The sensitivity and specificity of MRI parameters is determined via correlation with the gold-standard of histopathology. Whole-mount histopathology of prostatectomy specimens can be digitally registered to in vivo imaging for correlation. When biomechanical-based deformable registration is employed to account for deformation during histopathology processing, the ex vivo biomechanical properties are required. However, these properties are altered by pathology fixation, and vary with disease. Hence, this study employs magnetic resonance elastography (MRE) to measure ex vivo prostate biomechanical properties before and after fixation. A quasi-static MRE method was employed to measure high resolution maps of Young’s modulus (E) before and after fixation of canine prostate and prostatectomy specimens (n  =  4) from prostate cancer patients who had previously received radiation therapy. For comparison, T 1, T 2 and apparent diffusion coefficient (ADC) were measured in parallel. E (kPa) varied across clinical anatomy and for histopathology-identified tumor: peripheral zone: 99(±22), central gland: 48(±37), tumor: 85(±53), and increased consistently with fixation (factor of 11  ±  5 p  <  0.02). T 2 decreased consistently with fixation, while changes in T 1 and ADC were more complex and inconsistent. The biomechanics of the clinical prostate specimens varied greatly with fixation, and to a lesser extent with disease and anatomy. The data obtained will improve the precision of prostate pathology correlation, leading to more accurate disease detection and targeting.

  9. Prognostic predictability of the new American Joint Committee on Cancer 8th staging system for distal bile duct cancer: limited usefulness compared with the 7th staging system.

    PubMed

    Kang, Jae Seung; Lee, Seungyeoun; Son, Donghee; Han, Youngmin; Lee, Kyung Bun; Kim, Jae Ri; Kwon, Wooil; Kim, Sun-Whe; Jang, Jin-Young

    2018-02-01

    The new 8th American Joint Committee on Cancer (AJCC) staging has recently been released and there are major changes in distal bile duct (DBD) cancer staging. However, clinical validation is needed before the changes can be widely implemented. This study was performed to evaluate the prognostic predictability of the 8th AJCC staging compared with that of the 7th using C statistics. A total of 293 consecutive patients who had curative-intended surgery were enrolled. There was no significant difference of the 5-year survival rate between 7th T1 and T2 (P = 0.123), but significant difference between T2 and T3 (P = 0.039). There were significant differences in pairwise comparisons between the 8th T stage (T1 vs. T2, P = 0.001; T2 vs. T3, P = 0.014). The number of regional lymph node metastases also showed prognostic predictability. The 8th T and N stage both showed comparable prognostic predictability with the 7th (95% confidential intervals for C; T, -0.043 -0.097, N, -0.001 - 0.008). The 8th AJCC staging for DBD cancer does not have better prognostic predictability than the 7th stage does. The previous pathologic results would become useless unless they were reviewed entirely. Therefore, introduction of the AJCC 8th staging has to be reconsidered, especially for new T staging. © 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

  10. Myocardial effective transverse relaxation time T2* Correlates with left ventricular wall thickness: A 7.0 T MRI study.

    PubMed

    Huelnhagen, Till; Hezel, Fabian; Serradas Duarte, Teresa; Pohlmann, Andreas; Oezerdem, Celal; Flemming, Bert; Seeliger, Erdmann; Prothmann, Marcel; Schulz-Menger, Jeanette; Niendorf, Thoralf

    2017-06-01

    Myocardial effective relaxation time T2* is commonly regarded as a surrogate for myocardial tissue oxygenation. However, it is legitimate to assume that there are multiple factors that influence T2*. To this end, this study investigates the relationship between T2* and cardiac macromorphology given by left ventricular (LV) wall thickness and left ventricular radius, and provides interpretation of the results in the physiological context. High spatio-temporally resolved myocardial CINE T2* mapping was performed in 10 healthy volunteers using a 7.0 Tesla (T) full-body MRI system. Ventricular septal wall thickness, left ventricular inner radius, and T2* were analyzed. Macroscopic magnetic field changes were elucidated using cardiac phase-resolved magnetic field maps. Ventricular septal T2* changes periodically over the cardiac cycle, increasing in systole and decreasing in diastole. Ventricular septal wall thickness and T2* showed a significant positive correlation, whereas the inner LV radius and T2* were negatively correlated. The effect of macroscopic magnetic field gradients on T2* can be considered minor in the ventricular septum. Our findings suggest that myocardial T2* is related to tissue blood volume fraction. Temporally resolved T2* mapping could be beneficial for myocardial tissue characterization and for understanding cardiac (patho)physiology in vivo. Magn Reson Med 77:2381-2389, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

  11. FInvestigation of enhancement mode HfO2 insulated N-polarity GaN/InN/GaN/In0.9Al0.1N heterostructure MISHEMT for high-frequency applications

    NASA Astrophysics Data System (ADS)

    Mohanbabu, A.; Mohankumar, N.; Godwin Raj, D.; Sarkar, Partha

    2017-08-01

    In this paper, we examined normally-OFF N-polar InN-channel Metal insulated semiconductor high-electron mobility transistors (MISHEMTs) device with a relaxed In0.9Al0.1N buffer layer. In addition, the enhancement-mode operation of the N-polar structure was investigated. The effect of scaling in N-polar MISHEMT, such as the dielectric and the channel thickness, alter the electrical behavior of the device. We have achieved a maximum drain current of 1.17 A/mm, threshold voltage (VT) =0.728 V, transconductance (gm) of 2.9 S mm-1, high ION/IOFF current ratio of 3.23×103, lowest ON-state resistance (RON) of 0.41 Ω mm and an intrinsic delay time (τ) of 1.456 Fs along with high-frequency performance with ft/ fmaxof 90 GHz/109 GHz and 180 GHz/260 GHz for TCH =0.5 nm at Vds =0.5 V and 1.0 V. The numerically simulated results of highly confined GaN/InN/GaN/In0.9Al0.1N heterostructure MISHEMT exhibits outstanding potential as one of the possibility to replace presently used N-polar MISHEMTs for delivering high power density and frequency at RF/power amplifier applications.

  12. A High RORγT/CD3 Ratio is a Strong Prognostic Factor for Postoperative Survival in Advanced Colorectal Cancer: Analysis of Helper T Cell Lymphocytes (Th1, Th2, Th17 and Regulatory T Cells).

    PubMed

    Yoshida, Naohiro; Kinugasa, Tetsushi; Miyoshi, Hiroaki; Sato, Kensaku; Yuge, Kotaro; Ohchi, Takafumi; Fujino, Shinya; Shiraiwa, Sachiko; Katagiri, Mitsuhiro; Akagi, Yoshito; Ohshima, Koichi

    2016-03-01

    Tumor-infiltrating lymphocytes (TILs), part of the host immune response, have been widely reported as influential factors in the tumor microenvironment for the clinical outcome of colorectal cancer (CRC). However, the network of helper T cells is very complex, and which T-cell subtypes affect the progression of CRC and postoperative prognosis remains unclear. This study investigated the expression of several subtypes of TILs including T helper type 1 (Th1), Th2, Th17, and regulatory T (Treg) cells to determine their correlation with clinicopathologic features and postoperative prognosis. The study investigated the expression of TILs using immunohistochemistry of tissue microarray samples for 199 CRC patients. The number of each T-cell subtype infiltrating tumors was counted using ImageJ software. The relationship between TIL marker expression, clinicopathologic features, and prognosis was analyzed. A high RORγT/CD3 ratio (Th17 ratio) was significantly correlated with lymph node metastasis (p = 0.002), and a high of Foxp3/CD3 ratio (Treg ratio) was correlated with tumor location in the colon (p = 0.04), as shown by the Chi square test. In multivariate analysis, a high RORγT/CD3 ratio was the only independent prognostic factor for overall survival (p = 0.04; hazard ratio [HR], 1.84; 95% confidence interval [CI] 1.02-3.45). This study confirmed a high RORγT/CD3 ratio as a strong prognostic marker for postoperative survival. The immunohistochemistry results suggest that Th17 may affect lymph node metastasis in CRC. If new immunotherapies reducing Th17 expression are established, they may improve the efficiency of cancer treatment and prolong the survival of patients with CRC.

  13. Prognostic Significance of the Number of Positive Lymph Nodes in Women With T1-2N1 Breast Cancer Treated With Mastectomy: Should Patients With 1, 2, and 3 Positive Lymph Nodes Be Grouped Together?

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dai Kubicky, Charlotte, E-mail: charlottedai@gmail.com; Mongoue-Tchokote, Solange

    2013-04-01

    Purpose: To determine whether patients with 1, 2, or 3 positive lymph nodes (LNs) have similar survival outcomes. Methods and Materials: We analyzed the Surveillance, Epidemiology, and End Results registry of breast cancer patients diagnosed between 1990 and 2003. We identified 10,415 women with T1-2N1M0 breast cancer who were treated with mastectomy with no adjuvant radiation, with at least 10 LNs examined and 6 months of follow-up. The Kaplan-Meier method and log–rank test were used for survival analysis. Multivariate analysis was performed using the Cox proportional hazard model. Results: Median follow-up was 92 months. Ten-year overall survival (OS) and cause-specificmore » survival (CSS) were progressively worse with increasing number of positive LNs. Survival rates were 70%, 64%, and 60% (OS), and 82%, 76%, and 72% (CSS) for 1, 2, and 3 positive LNs, respectively. Pairwise log–rank test P values were <.001 (1 vs 2 positive LNs), <.001 (1 vs 3 positive LNs), and .002 (2 vs 3 positive LNs). Multivariate analysis showed that number of positive LNs was a significant predictor of OS and CSS. Hazard ratios increased with the number of positive LNs. In addition, age, primary tumor size, grade, estrogen receptor and progesterone receptor status, race, and year of diagnosis were significant prognostic factors. Conclusions: Our study suggests that patients with 1, 2, and 3 positive LNs have distinct survival outcomes, with increasing number of positive LNs associated with worse OS and CSS. The conventional grouping of 1-3 positive LNs needs to be reconsidered.« less

  14. Association of PHB 1630 C>T and MTHFR 677 C>T polymorphisms with breast and ovarian cancer risk in BRCA1/2 mutation carriers: results from a multicenter study

    PubMed Central

    Jakubowska, A; Rozkrut, D; Antoniou, A; Hamann, U; Scott, R J; McGuffog, L; Healy, S; Sinilnikova, O M; Rennert, G; Lejbkowicz, F; Flugelman, A; Andrulis, I L; Glendon, G; Ozcelik, H; Thomassen, M; Paligo, M; Aretini, P; Kantala, J; Aroer, B; von Wachenfeldt, A; Liljegren, A; Loman, N; Herbst, K; Kristoffersson, U; Rosenquist, R; Karlsson, P; Stenmark-Askmalm, M; Melin, B; Nathanson, K L; Domchek, S M; Byrski, T; Huzarski, T; Gronwald, J; Menkiszak, J; Cybulski, C; Serrano, P; Osorio, A; Cajal, T R; Tsitlaidou, M; Benítez, J; Gilbert, M; Rookus, M; Aalfs, C M; Kluijt, I; Boessenkool-Pape, J L; Meijers-Heijboer, H E J; Oosterwijk, J C; van Asperen, C J; Blok, M J; Nelen, M R; van den Ouweland, A M W; Seynaeve, C; van der Luijt, R B; Devilee, P; Easton, D F; Peock, S; Frost, D; Platte, R; Ellis, S D; Fineberg, E; Evans, D G; Lalloo, F; Eeles, R; Jacobs, C; Adlard, J; Davidson, R; Eccles, D; Cole, T; Cook, J; Godwin, A; Bove, B; Stoppa-Lyonnet, D; Caux-Moncoutier, V; Belotti, M; Tirapo, C; Mazoyer, S; Barjhoux, L; Boutry-Kryza, N; Pujol, P; Coupier, I; Peyrat, J-P; Vennin, P; Muller, D; Fricker, J-P; Venat-Bouvet, L; Johannsson, O Th; Isaacs, C; Schmutzler, R; Wappenschmidt, B; Meindl, A; Arnold, N; Varon-Mateeva, R; Niederacher, D; Sutter, C; Deissler, H; Preisler-Adams, S; Simard, J; Soucy, P; Durocher, F; Chenevix-Trench, G; Beesley, J; Chen, X; Rebbeck, T; Couch, F; Wang, X; Lindor, N; Fredericksen, Z; Pankratz, V S; Peterlongo, P; Bonanni, B; Fortuzzi, S; Peissel, B; Szabo, C; Mai, P L; Loud, J T; Lubinski, J

    2012-01-01

    Background: The variable penetrance of breast cancer in BRCA1/2 mutation carriers suggests that other genetic or environmental factors modify breast cancer risk. Two genes of special interest are prohibitin (PHB) and methylene-tetrahydrofolate reductase (MTHFR), both of which are important either directly or indirectly in maintaining genomic integrity. Methods: To evaluate the potential role of genetic variants within PHB and MTHFR in breast and ovarian cancer risk, 4102 BRCA1 and 2093 BRCA2 mutation carriers, and 6211 BRCA1 and 2902 BRCA2 carriers from the Consortium of Investigators of Modifiers of BRCA1 and BRCA2 (CIMBA) were genotyped for the PHB 1630 C>T (rs6917) polymorphism and the MTHFR 677 C>T (rs1801133) polymorphism, respectively. Results: There was no evidence of association between the PHB 1630 C>T and MTHFR 677 C>T polymorphisms with either disease for BRCA1 or BRCA2 mutation carriers when breast and ovarian cancer associations were evaluated separately. Analysis that evaluated associations for breast and ovarian cancer simultaneously showed some evidence that BRCA1 mutation carriers who had the rare homozygote genotype (TT) of the PHB 1630 C>T polymorphism were at increased risk of both breast and ovarian cancer (HR 1.50, 95%CI 1.10–2.04 and HR 2.16, 95%CI 1.24–3.76, respectively). However, there was no evidence of association under a multiplicative model for the effect of each minor allele. Conclusion: The PHB 1630TT genotype may modify breast and ovarian cancer risks in BRCA1 mutation carriers. This association need to be evaluated in larger series of BRCA1 mutation carriers. PMID:22669161

  15. DW MRI at 3.0 T versus FDG PET/CT for detection of malignant pulmonary tumors.

    PubMed

    Zhang, Jian; Cui, Long-Biao; Tang, Xing; Ren, Xin-Ling; Shi, Jie-Ran; Yang, Hai-Nan; Zhang, Yan; Li, Zhi-Kui; Wu, Chang-Gui; Jian, Wen; Zhao, Feng; Ti, Xin-Yu; Yin, Hong

    2014-02-01

    Emerging evidence suggests that diffusion-weighted magnetic resonance imaging (DW MRI) could be useful for tumor detection with N and M staging of lung cancer in place of fluorine 18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT). DW MRI at 3.0 T and FDG PET/CT were performed before therapy in 113 patients with pulmonary nodules. Mean apparent diffusion coefficient (ADC), maximal standardized uptake value (SUVmax ) and Ki-67 scores were assessed. Quantitatively, specificity and accuracy of ADC (91.7 and 92.9%, respectively) were significantly higher than those of SUVmax (66.7 and 77.9% respectively, p < 0.05), although sensitivity was not significantly different between them (93.5 and 83.1%, p > 0.05). Qualitatively, sensitivity, specificity and accuracy of DW MRI (96.1, 83.3 and 92.0%, respectively) were also not significantly different from that of FDG PET/CT (88.3, 83.3 and 86.7%, respectively, p > 0.05). Significant negative correlation was found between Ki-67 score and ADC (r = -0.66, p < 0.05), ADC and SUVmax (r = -0.37, p < 0.05), but not between Ki-67 score and SUVmax (r = -0.11, p > 0.05). In conclusion, quantitative and qualitative assessments for detection of malignant pulmonary tumors with DW MRI at 3.0 T are superior to those with FDG PET/CT. Furthermore, ADC could predict the malignancy of lung cancer. © 2013 UICC.

  16. Discovery of N-(4-aryl-5-aryloxy-thiazol-2-yl)-amides as potent RORγt inverse agonists.

    PubMed

    Wang, Yonghui; Yang, Ting; Liu, Qian; Ma, Yingli; Yang, Liuqing; Zhou, Ling; Xiang, Zhijun; Cheng, Ziqiang; Lu, Sijie; Orband-Miller, Lisa A; Zhang, Wei; Wu, Qianqian; Zhang, Kathleen; Li, Yi; Xiang, Jia-Ning; Elliott, John D; Leung, Stewart; Ren, Feng; Lin, Xichen

    2015-09-01

    A novel series of N-(4-aryl-5-aryloxy-thiazol-2-yl)-amides as RORγt inverse agonists was discovered. Binding mode analysis of a RORγt partial agonist (2c) revealed by co-crystal structure in RORγt LBD suggests that the inverse agonists do not directly interfere with the interaction between H12 and the RORγt LBD. Detailed SAR exploration led to identification of potent RORγt inverse agonists such as 3m with a pIC50 of 8.0. Selected compounds in the series showed reasonable activity in Th17 cell differentiation assay as well as low intrinsic clearance in mouse liver microsomes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Is neoadjuvant chemoradiation with dose-escalation and consolidation chemotherapy sufficient to increase surgery-free and distant metastases-free survival in baseline cT3 rectal cancer?

    PubMed

    São Julião, Guilherme Pagin; Habr-Gama, Angelita; Vailati, Bruna Borba; Aguilar, Patricia Bailão; Sabbaga, Jorge; Araújo, Sérgio Eduardo Alonso; Mattacheo, Adrian; Alexandre, Flavia Andrea; Fernandez, Laura Melina; Gomes, Diogo Bugano; Gama-Rodrigues, Joaquim; Perez, Rodrigo Oliva

    2018-01-01

    Patients with cT3 rectal cancer are less likely to develop complete response to neoadjuvant chemoradiation (nCRT) and still face significant risk for systemic relapse. In this setting, radiation (RT) dose-escalation and consolidation chemotherapy in "extended" nCRT regimens have been suggested to improve primary tumor response and decrease the risks of systemic recurrences. For these reasons we compared surgery-free and distant-metastases free survival among cT3 patients undergoing standard or extended nCRT. Patients with distal and non-metastatic T3 rectal cancer managed by nCRT were retrospectively reviewed. Patients undergoing standard CRT (50.4 Gy and 2 cycles of 5FU-based chemotherapy) were compared to those undergoing extended CRT (54 Gy and 6 cycles of 5FU-based chemotherapy). Patients were assessed for tumor response at 8-10 weeks. Patients with complete clinical response (cCR) underwent organ-preservation strategy (Watch & Wait). Patients were referred to salvage surgery in the event of local recurrence during follow-up. Cox's logistic regression was performed to identify independent features associated with improved surgery-free survival after cCR and distant-metastases-free survival. 155 patients underwent standard and 66 patients extended CRT. Patients undergoing extended CRT were more likely to harbor larger initial tumor size (p = 0.04), baseline nodal metastases (cN+; p < 0.001) and higher tumor location (p = 0.02). Cox-regression analysis revealed that the type of nCRT regimen was not independently associated with distinct surgery-free survival after cCR or distant-metastases-free survival (p > 0.05). Dose-escalation and consolidation chemotherapy are insufficient to increase long-term surgery-free survival among cT3 rectal cancer patients and provides no advantage in distant metastases-free survival. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights

  18. Evaluating Mesorectal Lymph Nodes in Rectal Cancer Before and After Neoadjuvant Chemoradiation Using Thin-Section T2-Weighted Magnetic Resonance Imaging

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Koh, Dow-Mu; Chau, Ian; Tait, Diana

    2008-06-01

    Purpose: To apply thin-section T2-weighted magnetic resoance imaging (MRI) to evaluate the number, size, distribution, and morphology of benign and malignant mesorectal lymph nodes before and after chemoradiation treatment compared with histopathologic findings. Methods and Materials: Twenty-five patients with poor-risk adenocarcinoma of the rectum treated with neoadjuvant chemoradiation were evaluated prospectively. Thin-section T2-weighted MR images obtained before and after chemoradiation treatment were independently reviewed in consensus by 2 expert radiologists to determine the tumor stage, nodal size, nodal distribution, and nodal stage. Total mesorectal excision surgery after chemoradiation allowed MR nodal stage to be compared with histopathology using {kappa} statistics.more » Nodal downstaging was compared using the Chi-square test. Results: Before chemoradiation, 152 mesorectal nodes were visible (mean, 6.2 mm; 100 benign, 52 malignant) and 4 of 52 malignant nodes were in contact with the mesorectal fascia. The nodal staging was 7/25 N0, 10/25 N1, and 7/25 N2. After chemoradiation, only 29 nodes (mean, 4.1 mm; 24 benign, 5 malignant) were visible, and none were in contact with the mesorectal fascia. Nodal downstaging was observed: 20/25 N0 and 5/25 N1 (p < 0.01, Chi-square test). There was good agreement between MRI and pathologic T-staging ({kappa} = 0.64) and N-staging ({kappa} = 0.65) after chemoradiation. Conclusions: Neoadjuvant chemoradiation treatment resulted in a decrease in size and number of malignant- and benign-appearing mesorectal nodes on MRI. Nodal downstaging and nodal regression from the mesorectal fascia were observed after treatment. MRI is a useful tool for assessing nodal response to neoadjuvant treatment.« less

  19. Recursive partition analysis of peritoneal and systemic recurrence in patients with gastric cancer who underwent D2 gastrectomy: Implications for neoadjuvant therapy consideration.

    PubMed

    Chang, Jee Suk; Kim, Kyung Hwan; Keum, Ki Chang; Noh, Sung Hoon; Lim, Joon Seok; Kim, Hyo Song; Rha, Sun Young; Lee, Yong Chan; Hyung, Woo Jin; Koom, Woong Sub

    2016-12-01

    To classify patients with nonmetastatic advanced gastric cancer who underwent D2-gastrectomy into prognostic groups based on peritoneal and systemic recurrence risks. Between 2004 and 2007, 1,090 patients with T3-4 or N+ gastric cancer were identified from our registry. Recurrence rates were estimated using a competing-risk analysis. Different prognostic groups were defined using recursive partitioning analysis (RPA). Median follow-up was 7 years. In the RPA-model for peritoneal recurrence risk, the initial node was split by T stage, indicating that differences between patients with T1-3 and T4 cancer were the greatest. The 5-year peritoneal recurrence rates for patients with T4 (n = 627) and T1-3 (n = 463) disease were 34.3% and 9.1%, respectively. N stage and neural invasion had an additive impact on high-risk patients. The RPA model for systemic relapse incorporated N stage alone and gave two terminal nodes: N0-2 (n = 721) and N3 (n = 369). The 5-year cumulative incidences were 7.7% and 24.5%, respectively. We proposed risk stratification models of peritoneal and systemic recurrence in patients undergoing D2-gastrectomy. This classification could be used for stratification protocols in future studies evaluating adjuvant therapies such as preoperative chemoradiotherapy. J. Surg. Oncol. 2016;114:859-864. © 2016 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  20. Recommendations for neoadjuvant pathologic staging (ypTNM) of cancer of the esophagus and esophagogastric junction for the 8th edition AJCC/UICC staging manuals.

    PubMed

    Rice, Thomas W; Ishwaran, Hemant; Kelsen, David P; Hofstetter, Wayne L; Apperson-Hansen, Carolyn; Blackstone, Eugene H

    2016-11-01

    We report analytic and consensus processes that produced recommendations for neoadjuvant pathologic stage groups (ypTNM) of esophageal and esophagogastric junction cancer for the AJCC/UICC cancer staging manuals, 8th edition. The Worldwide Esophageal Cancer Collaboration provided data for 22,654 patients with epithelial esophageal cancers; 7,773 had pathologic assessment after neoadjuvant therapy. Risk-adjusted survival for each patient was developed. Random forest analysis identified data-driven neoadjuvant pathologic stage groups wherein survival decreased monotonically with increasing group, was distinctive between groups, and homogeneous within groups. An additional analysis produced data-driven anatomic neoadjuvant pathologic stage groups based only on ypT, ypN, and ypM categories. The AJCC Upper GI Task Force, by smoothing, simplifying, expanding, and assessing clinical applicability, produced consensus neoadjuvant pathologic stage groups. Grade and location were much less discriminating for stage grouping ypTNM than pTNM. Data-driven stage grouping without grade and location produced nearly identical groups for squamous cell carcinoma and adenocarcinoma. However, ypTNM groups and their associated survival differed from pTNM. The need for consensus process was minimal. The consensus groups, identical for both cell types were as follows: ypStage I comprised ypT0-2N0M0; ypStage II ypT3N0M0; ypStage IIIA ypT0-2N1M0; ypStage IIIB ypT3N1M0, ypT0-3N2, and ypT4aN0M0; ypStage IVA ypT4aN1-2, ypT4bN0-2, and ypTanyN3M0; and ypStage IVB ypTanyNanyM1. Absence of equivalent pathologic (pTNM) categories for the peculiar neoadjuvant pathologic categories ypTisN0-3M0 and ypT0N0-3M0, dissimilar stage group compositions, and markedly different early- and intermediate-stage survival necessitated a unified, unique set of stage grouping for patients of either cell type who receive neoadjuvant therapy. © 2016 International Society for Diseases of the Esophagus.

  1. Tumor size as a prognostic factor in patients with advanced gastric cancer in the lower third of the stomach.

    PubMed

    Wang, Hong-Mei; Huang, Chang-Ming; Zheng, Chao-Hui; Li, Ping; Xie, Jian-Wei; Wang, Jia-Bin; Lin, Jian-Xian; Lu, Jun

    2012-10-14

    To explore the impact of tumor size on outcomes in patients with advanced gastric cancer in the lower third of the stomach. We retrospectively analyzed the clinical records of 430 patients with advanced gastric cancer in the lower third of the stomach who underwent distal subtotal gastrectomy and D2 lymphadenectomy in our hospital from January 1998 to June 2004. Receiver-operating characteristic (ROC) curve analysis was used to determine the appropriate cutoff value for tumor size, which was measured as maximum tumor diameter. Based on this cutoff value, patients were divided into two groups: those with large-sized tumors (LSTs) and those with small-sized tumors (SSTs). The correlations between other clinicopathologic factors and tumor size were investigated, and the 5-year overall survival (OS) rate was compared between the two groups. Potential prognostic factors were evaluated by univariate Kaplan-Meier survival analysis and multivariate Cox's proportional hazard model analysis. The 5-year OS rates in the two groups were compared according to pT stage and pN stage. The 5-year OS rate in the 430 patients with advanced gastric cancer in the lower third of the stomach was 53.7%. The mean ± SD tumor size was 4.9 ± 1.9 cm, and the median tumor size was 5.0 cm. ROC analysis indicated that the sensitivity and specificity results for the appropriate tumor size cutoff value of 4.8 cm were 80.0% and 68.2%, respectively (AUC = 0.795, 95%CI: 0.751-0.839, P = 0.000). Using this cutoff value, 222 patients (51.6%) had LSTs (tumor size ≥ 4.8 cm) and 208 (48.4%) had SSTs (tumor size < 4.8 cm). Tumor size was significantly correlated with histological type (P = 0.039), Borrmann type (P = 0.000), depth of tumor invasion (P = 0.000), lymph node metastasis (P = 0.000), tumor-nodes metastasis stage (P = 0.000), mean number of metastatic lymph nodes (P = 0.000) and metastatic lymph node ratio (P = 0.000). Patients with LSTs had a significantly lower 5-year OS rate than those with

  2. Total gastrectomy reconstructed by interposition of a jejunal J pouch with preservation of hepatic vagus branch and lower esophageal sphincter for T2 gastric cancer without lymph node metastasis.

    PubMed

    Tomita, Ryouichi; Tanjoh, Katsuhisa; Fujisaki, Shigeru

    2004-01-01

    In order to improve postgastrectomy disorders of patients with T2 (MP or SS) gastric cancer without lymph node metastasis, which mainly locates in the middle third of stomach, we have performed a total gastrectomy preserving both hepatic vagus branches and the lower esophageal sphincter as a function-preserving surgical procedure. In the present study, the application criteria and points of the technique are outlined, and postoperative quality of life is clinically investigated. Twenty-four subjects who underwent this surgical operation (group A; 16 men and 8 women subjects aged 46 to 73 years, mean age 62.2 years) were interviewed regarding appetite, weight loss, reflux esophagitis, dumping syndrome, and microgastria. Cholelithiasis following total gastrectomy was also checked by abdominal ultrasonography. Group A was compared with 26 cases of conventional total gastrectomy with D2 lymphadenectomy, excision of lower esophageal sphincter, total vagotomy, and single jejunal interposition (B group; 19 men and 7 women subjects aged 42 to 75 years, mean age 64.8 years). Application criteria of the technique: Included were cases with T2 cancer of N0 mainly localizing at the middle-third of the stomach which was 4 cm or further in distance from the oral-side margin of the cancer to the esophagogastric mucosa junction. Points of the technique: In lymphadenectomy, hepatic branches of the vagal nerve only preserved. To preserve lower esophageal sphincter, the abdominal esophagus was severed at the level of His angle to the longitudinal axis of the esophagus. Substitute stomach was created as a 15-cm jejunal pouch with a 5-cm-long jejunal conduit for isoperistaltic movement. In group A the food ingestion rate was significantly greater than that of group B (P<0.001) at 6 months and 2.0 years after operation, with no reflux esophagitis or dumping syndrome being noticed at 2.0 years after operation. In group B, loss of appetite 2.0 years after operation was significantly higher

  3. High intensity focused ultrasound (HIFU) for treatment of T1/T2 prostate cancer

    NASA Astrophysics Data System (ADS)

    Sanghvi, N.; Gardner, T.; Koch, M.

    2003-04-01

    This FDA approved phase I/II clinical trial is to evaluate the safety and efficacy of the Sonablate device (Focus Surgery, Inc.) for the treatment of organ confined prostate cancer. 20 patients with biopsy proven prostate cancer, Gleason <=7 and PSA <=10 were treated under general anesthesia. Outcome data included serum PSA collected at day 3, 14, 30, 90, 180, PSA nadir (mean/median), and biopsy results at 6 months. Quality of life was assessed using the International Prostate Symptom Score, International Impotence and Erectile Function score, and the SF-36 health survey. The mean patient age is 62.0, Gleason score of 6.18, PSA of 5.2, and prostate size 26.0 gm. Mean PSA results were 5.62, 44, 20, 1.68, 0.87, and 0.44 ng/ml at screening, 48-72 hours, 14 days, 30 days, 90 days and 180 days, respectively. There was one patient (9%) with a positive TRUS biopsy at 6 months, which resulted in a retreatment. There were no rectal injuries. Average pre-treatment IPSS, IIEF, and SF-36 scores were 9.55, 16.1, and 103.5. At the 30 day follow-up, they were 18.3, 3, and 97.4, respectively. HIFU is a minimally invasive modality that achieves complete prostatic ablation and is efficacious in the treatment of low-stage prostate cancer.

  4. Regional Delivery of Chimeric Antigen Receptor-Engineered T Cells Effectively Targets HER2+ Breast Cancer Metastasis to the Brain.

    PubMed

    Priceman, Saul J; Tilakawardane, Dileshni; Jeang, Brook; Aguilar, Brenda; Murad, John P; Park, Anthony K; Chang, Wen-Chung; Ostberg, Julie R; Neman, Josh; Jandial, Rahul; Portnow, Jana; Forman, Stephen J; Brown, Christine E

    2018-01-01

    Purpose: Metastasis to the brain from breast cancer remains a significant clinical challenge, and may be targeted with CAR-based immunotherapy. CAR design optimization for solid tumors is crucial due to the absence of truly restricted antigen expression and potential safety concerns with "on-target off-tumor" activity. Here, we have optimized HER2-CAR T cells for the treatment of breast to brain metastases, and determined optimal second-generation CAR design and route of administration for xenograft mouse models of breast metastatic brain tumors, including multifocal and leptomeningeal disease. Experimental Design: HER2-CAR constructs containing either CD28 or 4-1BB intracellular costimulatory signaling domains were compared for functional activity in vitro by measuring cytokine production, T-cell proliferation, and tumor killing capacity. We also evaluated HER2-CAR T cells delivered by intravenous, local intratumoral, or regional intraventricular routes of administration using in vivo human xenograft models of breast cancer that have metastasized to the brain. Results: Here, we have shown that HER2-CARs containing the 4-1BB costimulatory domain confer improved tumor targeting with reduced T-cell exhaustion phenotype and enhanced proliferative capacity compared with HER2-CARs containing the CD28 costimulatory domain. Local intracranial delivery of HER2-CARs showed potent in vivo antitumor activity in orthotopic xenograft models. Importantly, we demonstrated robust antitumor efficacy following regional intraventricular delivery of HER2-CAR T cells for the treatment of multifocal brain metastases and leptomeningeal disease. Conclusions: Our study shows the importance of CAR design in defining an optimized CAR T cell, and highlights intraventricular delivery of HER2-CAR T cells for treating multifocal brain metastases. Clin Cancer Res; 24(1); 95-105. ©2017 AACR . ©2017 American Association for Cancer Research.

  5. Introducing ionic and/or hydrogen bonds into the SAM//Ga2O3 top-interface of Ag(TS)/S(CH2)nT//Ga2O3/EGaIn junctions.

    PubMed

    Bowers, Carleen M; Liao, Kung-Ching; Yoon, Hyo Jae; Rappoport, Dmitrij; Baghbanzadeh, Mostafa; Simeone, Felice C; Whitesides, George M

    2014-06-11

    Junctions with the structure Ag(TS)/S(CH2)nT//Ga2O3/EGaIn (where S(CH2)nT is a self-assembled monolayer, SAM, of n-alkanethiolate bearing a terminal functional group T) make it possible to examine the response of rates of charge transport by tunneling to changes in the strength of the interaction between T and Ga2O3. Introducing a series of Lewis acidic/basic functional groups (T = -OH, -SH, -CO2H, -CONH2, and -PO3H) at the terminus of the SAM gave values for the tunneling current density, J(V) in A/cm(2), that were indistinguishable (i.e., differed by less than a factor of 3) from the values observed with n-alkanethiolates of equivalent length. The insensitivity of the rate of tunneling to changes in the terminal functional group implies that replacing weak van der Waals contact interactions with stronger hydrogen- or ionic bonds at the T//Ga2O3 interface does not change the shape (i.e., the height or width) of the tunneling barrier enough to affect rates of charge transport. A comparison of the injection current, J0, for T = -CO2H, and T = -CH2CH3--two groups having similar extended lengths (in Å, or in numbers of non-hydrogen atoms)--suggests that both groups make indistinguishable contributions to the height of the tunneling barrier.

  6. A nomogram to predict the survival of stage IIIA-N2 non-small cell lung cancer after surgery.

    PubMed

    Mao, Qixing; Xia, Wenjie; Dong, Gaochao; Chen, Shuqi; Wang, Anpeng; Jin, Guangfu; Jiang, Feng; Xu, Lin

    2018-04-01

    Postoperative survival of patients with stage IIIA-N2 non-small cell lung cancer (NSCLC) is highly heterogeneous. Here, we aimed to identify variables associated with postoperative survival and develop a tool for survival prediction. A retrospective review was performed in the Surveillance, Epidemiology, and End Results database from January 2004 to December 2009. Significant variables were selected by use of the backward stepwise method. The nomogram was constructed with multivariable Cox regression. The model's performance was evaluated by concordance index and calibration curve. The model was validated via an independent cohort from the Jiangsu Cancer Hospital Lung Cancer Center. A total of 1809 patients with stage IIIA-N2 NSCLC who underwent surgery were included in the training cohort. Age, sex, grade, histology, tumor size, visceral pleural invasion, positive lymph nodes, lymph nodes examined, and surgery type (lobectomy vs pneumonectomy) were identified as significant prognostic variables using backward stepwise method. A nomogram was developed from the training cohort and validated using an independent Chinese cohort. The concordance index of the model was 0.673 (95% confidence interval, 0.654-0.692) in training cohort and 0.664 in validation cohort (95% confidence interval, 0.614-0.714). The calibration plot showed optimal consistency between nomogram predicted survival and observed survival. Survival analyses demonstrated significant differences between different subgroups stratified by prognostic scores. This nomogram provided the individual survival prediction for patients with stage IIIA-N2 NSCLC after surgery, which might benefit survival counseling for patients and clinicians, clinical trial design and follow-up, as well as postoperative strategy-making. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  7. Detection of the index tumour and tumour volume in prostate cancer using T2-weighted and diffusion-weighted magnetic resonance imaging (MRI) alone.

    PubMed

    Rud, Erik; Klotz, Dagmar; Rennesund, Kristin; Baco, Eduard; Berge, Viktor; Lien, Diep; Svindland, Aud; Lundeby, Eskild; Berg, Rolf E; Eri, Lars M; Eggesbø, Heidi B

    2014-12-01

    To examine the performance of T2-weighted (T2W) and diffusion-weighted (DW) magnetic resonance imaging (MRI) for detecting the index tumour in patients with prostate cancer and to examine the agreement between MRI and histology when assessing tumour volume (TV) and overall tumour burden. The study included 199 consecutive patients with biopsy confirmed prostate cancer randomised to MRI before radical prostatectomy from December 2009 to July 2012. MRI-detected tumours (MRTs) were ranked from 1 to 3 according to decreasing volume and were compared with histologically detected tumours (HTs) ranked from 1 to 3, with HT 1 = index tumour. Whole-mount section histology was used as a reference standard. The TVs of true-positive MRTs (MRTVs 1-3) were compared with the TVs found by histology (HTVs 1-3). All tumours were registered on a 30-sector map and by classifying each sector as positive/negative, the rate of true-positive and -negative sectors was calculated. The detection rate for the HT 1 (index tumour) was 92%; HT 2, 45%; and HT 3, 37%. The MRTV 1-3 vs the HTV 1-3 were 2.8 mL vs 4.0 mL (index tumour, P < 0.001), 1.0 mL vs 0.9 mL (tumour 2, P = 0.413), and 0.6 mL vs 0.5 mL (tumour 3, P = 0.492). The rate of true-positive and -negative sectors was 50% and 88%, κ = 0.39. A combination of T2W and DW MRI detects the index tumour in 92% of cases, although MRI underestimates both TV and tumour burden compared with histology. © 2014 The Authors. BJU International © 2014 BJU International.

  8. DPYD*2A and MTHFR C677T predict toxicity and efficacy, respectively, in patients on chemotherapy with 5-fluorouracil for colorectal cancer.

    PubMed

    Nahid, Noor Ahmed; Apu, Mohd Nazmul Hasan; Islam, Md Reazul; Shabnaz, Samia; Chowdhury, Surid Mohammad; Ahmed, Maizbha Uddin; Nahar, Zabun; Islam, Md Siddiqul; Islam, Mohammad Safiqul; Hasnat, Abul

    2018-01-01

    Significant inter-individual variation in the sensitivity to 5-fluorouracil (5-FU) represents a major therapeutic hindrance either by impairing drug response or inducing adverse drug reactions (ADRs). This study aimed at exploring the cause behind this inter-individual alterations in consequences of 5-fluorouracil-based chemotherapy by investigating the effects of DPYD*2A and MTHFR C677T polymorphisms on toxicity and response of 5-FU in Bangladeshi colorectal cancer patients. Colorectal cancer patients (n = 161) receiving 5-FU-based chemotherapy were prospectively enrolled. DPYD and MTHFR polymorphisms were assessed in peripheral leukocytes. Multivariate analyses were applied to evaluate which variables could predict chemotherapy-induced toxicity and efficacy. Multivariate analyses showed that DPYD*2A polymorphism was a predictive factor (P = 0.023) for grade 3 and grade 4 5-fluorouracil-related toxicities. Although MTHFR C677T polymorphism might act as forecasters for grade 3 or grade 4 neutropenia, diarrhea, and mucositis, this polymorphism was found to increase significantly (P = 0.006) the response of 5-FU. DPYD*2A and MTHFR C677T polymorphisms could explain 5-FU toxicity or clinical outcome in Bangladeshi colorectal patients.

  9. A Prospective Study of Level IIB Nodal Metastasis (Supraretrospinal) in Clinically N0 Oral Squamous Cell Carcinoma in Indian Population.

    PubMed

    Chheda, Yogen P; Pillai, Sundaram K; Parikh, Devendra G; Dipayan, Nandy; Shah, Shakuntala V; Alaknanda, Gupta

    2017-06-01

    Oral cavity carcinoma is the most common cancer in Indian population. Metastatic nodal disease is the most important prognostic factor for oral cancers. In head and neck cancers with clinically N0 neck, standard selective neck dissection is performed by protecting the spinal accessory nerve to remove level IIA & IIB lymph nodes. The purpose of this study was to analyze the significance of level IIB dissection in patients of oral cavity cancer who underwent primary surgery with functional neck dissection. Two hundred ten patients with clinically N0 neck underwent neck dissection, where level IIB lymph nodes were dissected, labelled and processed separately. Among 210 patients of clinically N0 neck, 168 patients were pathologically N0 (80 %). Out of remaining 42 (20 %), 36 (17.14 %) were pN1 and 6 (2.86 %) were pN2. Among those with pN1 (36), level IB was involved in 24 patients (66.67 %) and level IIA was involved in 12 patients (33.33 %). Only 2 patients had involvement of level IIB lymph nodes. Among 6 patients of pN2 disease, 4 patients had simultaneous involvement of level IB and level IIA lymph nodes. Remaining 2 patients had isolated involvement of level III lymph nodes. Thus only 2 patients (< 1 %) out of 210 clinically N0 oral squamous cell carcinoma showed level IIB lymph node involvement. Thus we conclude that a frozen section of level 2a is advisable to decide the need for level 2b node dissection in clinically N0 neck as the sensitivity of clinical evaluation is extremely low.

  10. The Norwegian PMS2 founder mutation c.989-1G > T shows high penetrance of microsatellite instable cancers with normal immunohistochemistry.

    PubMed

    Grindedal, Eli Marie; Aarset, Harald; Bjørnevoll, Inga; Røyset, Elin; Mæhle, Lovise; Stormorken, Astrid; Heramb, Cecilie; Medvik, Heidi; Møller, Pål; Sjursen, Wenche

    2014-01-01

    Using immunohistochemistry (IHC) to select cases for mismatch repair (MMR) genetic testing, we failed to identify a large kindred with the deleterious PMS2 mutation c.989-1G > T. The purpose of the study was to examine the sensitivity of IHC and microsatellite instability-analysis (MSI) to identify carriers of the mutation, and to estimate its penetrance and expressions. All carriers and obligate carriers of the mutation were identified. All cancer diagnoses were confirmed. IHC and MSI-analysis were performed on available tumours. Penetrances of cancers included in the Amsterdam and the Bethesda Criteria, for MSI-high tumours and MSI-high and low tumours were calculated by the Kaplan-Meier algorithm. Probability for co-segregation of the mutation and cancers by chance was 0.000004. Fifty-six carriers or obligate carriers were identified. There was normal staining for PMS2 in 15/18 (83.3%) of tumours included in the AMS1/AMS2/Bethesda criteria. MSI-analysis showed that 15/21 (71.4%) of tumours were MSI-high and 4/21 (19.0%) were MSI-low. Penetrance at 70 years was 30.6% for AMS1 cancers (colorectal cancers), 42.8% for AMS2 cancers, 47.2% for Bethesda cancers, 55.6% for MSI-high and MSI-low cancers and 52.2% for MSI-high cancers. The mutation met class 5 criteria for pathogenicity. IHC was insensitive in detecting tumours caused by the mutation. Penetrance of cancers that displayed MSI was 56% at 70 years. Besides colorectal cancers, the most frequent expressions were carcinoma of the endometrium and breast in females and stomach and prostate in males.

  11. The Norwegian PMS2 founder mutation c.989-1G > T shows high penetrance of microsatellite instable cancers with normal immunohistochemistry

    PubMed Central

    2014-01-01

    Background Using immunohistochemistry (IHC) to select cases for mismatch repair (MMR) genetic testing, we failed to identify a large kindred with the deleterious PMS2 mutation c.989-1G > T. The purpose of the study was to examine the sensitivity of IHC and microsatellite instability-analysis (MSI) to identify carriers of the mutation, and to estimate its penetrance and expressions. Methods All carriers and obligate carriers of the mutation were identified. All cancer diagnoses were confirmed. IHC and MSI-analysis were performed on available tumours. Penetrances of cancers included in the Amsterdam and the Bethesda Criteria, for MSI-high tumours and MSI-high and low tumours were calculated by the Kaplan-Meier algorithm. Results Probability for co-segregation of the mutation and cancers by chance was 0.000004. Fifty-six carriers or obligate carriers were identified. There was normal staining for PMS2 in 15/18 (83.3%) of tumours included in the AMS1/AMS2/Bethesda criteria. MSI-analysis showed that 15/21 (71.4%) of tumours were MSI-high and 4/21 (19.0%) were MSI-low. Penetrance at 70 years was 30.6% for AMS1 cancers (colorectal cancers), 42.8% for AMS2 cancers, 47.2% for Bethesda cancers, 55.6% for MSI-high and MSI-low cancers and 52.2% for MSI-high cancers. Conclusions The mutation met class 5 criteria for pathogenicity. IHC was insensitive in detecting tumours caused by the mutation. Penetrance of cancers that displayed MSI was 56% at 70 years. Besides colorectal cancers, the most frequent expressions were carcinoma of the endometrium and breast in females and stomach and prostate in males. PMID:24790682

  12. PGE2 contributes to TGF-β induced T regulatory cell function in human non-small cell lung cancer

    PubMed Central

    Baratelli, Felicita; Lee, Jay M; Hazra, Saswati; Lin, Ying; Walser, Tonya C; Schaue, Dorthe; Pak, Peter S; Elashoff, David; Reckamp, Karen; Zhang, Ling; Fishbein, Michael C; Sharma, Sherven; Dubinett, Steven M

    2010-01-01

    CD4+CD25bright regulatory T cells (Treg) play an important role in cancer-mediated immunosuppression. We and others have previously shown that prostaglandin E2 (PGE2) and transforming growth factor beta (TGF-β) induce CD4+CD25brightFOXP3+Treg. Based on these studies, we investigated the requirement for PGE2 in Treg induction by TGF-β. TGF-β stimulation of human CD4+ T cells induced COX-2-dependent production of PGE2. PGE2-neutralizing antibody treatment significantly reduced the suppressive function of TGF-β-induced Treg (TGF-β-Treg) in vitro. TGF-β concentration measured in the plasma of non-small cell lung cancer (NSCLC) patients directly correlated with the frequency of circulating CD4+CD25brightFOXP3+T cells. Flow cytometry analysis showed increased FOXP3 expression in circulating CD4+CD25+HLA-DR- cells of lung cancer patients compared to control subjects. Immunohistochemical analysis revealed co-expression of TGF-β, COX-2, and FOXP3 in serial sections from resected lung tumor tissues. All together these observations suggest interplay between TGF-β and COX-2 in the induction of Treg activities. Interrupting TGF-β and PGE2 signaling may be important in therapeutic interventions that aim to limit Tregfunction in lung cancer. PMID:20733946

  13. Gallbladder Cancer: expert consensus statement

    PubMed Central

    Aloia, Thomas A; Járufe, Nicolas; Javle, Milind; Maithel, Shishir K; Roa, Juan C; Adsay, Volkan; Coimbra, Felipe J F; Jarnagin, William R

    2015-01-01

    An American Hepato-Pancreato-Biliary Association (AHPBA)-sponsored consensus meeting of expert panellists was convened on 15 January 2014 to review current evidence on the management of gallbladder carcinoma in order to establish practice guidelines. In summary, within high incidence areas, the assessment of routine gallbladder specimens should include the microscopic evaluation of a minimum of three sections and the cystic duct margin; specimens with dysplasia or proven cancer should be extensively sampled. Provided the patient is medically fit for surgery, data support the resection of all gallbladder polyps of >1.0 cm in diameter and those with imaging evidence of vascular stalks. The minimum staging evaluation of patients with suspected or proven gallbladder cancer includes contrasted cross-sectional imaging and diagnostic laparoscopy. Adequate lymphadenectomy includes assessment of any suspicious regional nodes, evaluation of the aortocaval nodal basin, and a goal recovery of at least six nodes. Patients with confirmed metastases to N2 nodal stations do not benefit from radical resection and should receive systemic and/or palliative treatments. Primary resection of patients with early T-stage (T1b–2) disease should include en bloc resection of adjacent liver parenchyma. Patients with T1b, T2 or T3 disease that is incidentally identified in a cholecystectomy specimen should undergo re-resection unless this is contraindicated by advanced disease or poor performance status. Re-resection should include complete portal lymphadenectomy and bile duct resection only when needed to achieve a negative margin (R0) resection. Patients with preoperatively staged T3 or T4 N1 disease should be considered for clinical trials of neoadjuvant chemotherapy. Following R0 resection of T2–4 disease in N1 gallbladder cancer, patients should be considered for adjuvant systemic chemotherapy and/or chemoradiotherapy. PMID:26172135

  14. Gallbladder cancer: expert consensus statement.

    PubMed

    Aloia, Thomas A; Járufe, Nicolas; Javle, Milind; Maithel, Shishir K; Roa, Juan C; Adsay, Volkan; Coimbra, Felipe J F; Jarnagin, William R

    2015-08-01

    An American Hepato-Pancreato-Biliary Association (AHPBA)-sponsored consensus meeting of expert panellists was convened on 15 January 2014 to review current evidence on the management of gallbladder carcinoma in order to establish practice guidelines. In summary, within high incidence areas, the assessment of routine gallbladder specimens should include the microscopic evaluation of a minimum of three sections and the cystic duct margin; specimens with dysplasia or proven cancer should be extensively sampled. Provided the patient is medically fit for surgery, data support the resection of all gallbladder polyps of >1.0 cm in diameter and those with imaging evidence of vascular stalks. The minimum staging evaluation of patients with suspected or proven gallbladder cancer includes contrasted cross-sectional imaging and diagnostic laparoscopy. Adequate lymphadenectomy includes assessment of any suspicious regional nodes, evaluation of the aortocaval nodal basin, and a goal recovery of at least six nodes. Patients with confirmed metastases to N2 nodal stations do not benefit from radical resection and should receive systemic and/or palliative treatments. Primary resection of patients with early T-stage (T1b-2) disease should include en bloc resection of adjacent liver parenchyma. Patients with T1b, T2 or T3 disease that is incidentally identified in a cholecystectomy specimen should undergo re-resection unless this is contraindicated by advanced disease or poor performance status. Re-resection should include complete portal lymphadenectomy and bile duct resection only when needed to achieve a negative margin (R0) resection. Patients with preoperatively staged T3 or T4 N1 disease should be considered for clinical trials of neoadjuvant chemotherapy. Following R0 resection of T2-4 disease in N1 gallbladder cancer, patients should be considered for adjuvant systemic chemotherapy and/or chemoradiotherapy. © 2015 International Hepato-Pancreato-Biliary Association.

  15. The Role of T Lymphocytes in Cancer Patients Undergoing Immunotherapy with Autologous Dendritic Cells

    PubMed Central

    Rodrigues, Cláudia M.; Matias, Bruna F.; Murta, Eddie F.C.; Michelin, Márcia A.

    2011-01-01

    Introduction: Cancer stems from mutations in specific genes that induce uncontrolled cell proliferation. Dendritic cells (DCs) are important immunologic cells and play a crucial role in the induction of an antitumour response. Patients and methods: We examined the immune response mediated by T lymphocytes, helper T cells, cytotoxic T cells, and regulatory T cells, as well as the cytokines [interleukin (IL)-2, IL-12, interferon (IFN)-γ, tumour necrosis factor (TNF)-α and IL-10], produced by these cell populations, in cancer patients (N = 7) undergoing immunotheraphy with autologous DCs. Results: We observed an initial increase in T helper cells (CD4+) expressing IL-2, IFN-γ, IL-12, TNF-α, and IL-10 after initiation of treatment, with statistically significant for the cytokines IL-2, TNF-α and IL-10. A similar significant effect was observed for IL-2-expressing cytotoxic T cells (CD8+). The percentage of total T cells (CD3+) remained elevated throughout immunotherapy. Regulatory T cells (CD25+/FOXP3+) only showed high percentage of their maximum value when analyzed the pretreatment levels, with statistically significant. Conclusion: Immunotherapy with DCs stimulated the immune response, as evidenced by an increase in percent fluorescence of most cell populations investigated during the specified treatment period. PMID:21603246

  16. The role of T lymphocytes in cancer patients undergoing immunotherapy with autologous dendritic cells.

    PubMed

    Rodrigues, Cláudia M; Matias, Bruna F; Murta, Eddie F C; Michelin, Márcia A

    2011-01-01

    Cancer stems from mutations in specific genes that induce uncontrolled cell proliferation. Dendritic cells (DCs) are important immunologic cells and play a crucial role in the induction of an antitumour response. We examined the immune response mediated by T lymphocytes, helper T cells, cytotoxic T cells, and regulatory T cells, as well as the cytokines [interleukin (IL)-2, IL-12, interferon (IFN)-γ, tumour necrosis factor (TNF)-α and IL-10], produced by these cell populations, in cancer patients (N = 7) undergoing immunotheraphy with autologous DCs. We observed an initial increase in T helper cells (CD4+) expressing IL-2, IFN-γ, IL-12, TNF-α, and IL-10 after initiation of treatment, with statistically significant for the cytokines IL-2, TNF-α and IL-10. A similar significant effect was observed for IL-2-expressing cytotoxic T cells (CD8+). The percentage of total T cells (CD3+) remained elevated throughout immunotherapy. Regulatory T cells (CD25+/FOXP3+) only showed high percentage of their maximum value when analyzed the pretreatment levels, with statistically significant. Immunotherapy with DCs stimulated the immune response, as evidenced by an increase in percent fluorescence of most cell populations investigated during the specified treatment period.

  17. Epi proColon® 2.0 CE: A Blood-Based Screening Test for Colorectal Cancer.

    PubMed

    Lamb, Yvette N; Dhillon, Sohita

    2017-04-01

    Epi proColon ® 2.0 CE is a blood-based test designed to aid in the early detection of colorectal cancer. The test comprises a qualitative assay for the polymerase chain reaction (PCR) detection of methylated Septin9 DNA, the presence of which is associated with colorectal cancer: however, positive results should be verified by colonoscopy or sigmoidoscopy. Epi proColon ® 2.0 CE discriminated between patients with colorectal cancer and healthy controls with high clinical sensitivity and specificity in pivotal case-control studies. The sensitivity of the test did not appear to be affected by the tumour location or by patient age or gender. In addition, limited data suggest that Epi proColon ® 2.0 CE discriminated between patients with colorectal cancer and healthy controls with higher sensitivity and generally similar specificity to that of the faecal immunochemical test, and with higher sensitivity and specificity to that of the guaiac-based faecal occult blood test (statistical data not available). In an observational study, most patients who refused colonoscopy for screening accepted a non-invasive test option as an alternative, and preferred Epi proColon ® 2.0 CE over a stool-based test. Large prospective trials of Epi proColon ® 2.0 CE in a screening setting will be required to further elucidate the cost-effectiveness of the test. Nevertheless, currently available data suggests that Epi proColon ® 2.0 CE has the potential to be a sensitive and convenient screening option for patients refusing screening by colonoscopy.

  18. 3.0 T plaque imaging.

    PubMed

    Hinton-Yates, Denise P; Cury, Ricardo C; Wald, Lawrence L; Wiggins, Graham C; Keil, Boris; Seethmaraju, Ravi; Gangadharamurthy, Dakshinamurthy; Ogilvy, Christopher S; Dai, Guangping; Houser, Stuart L; Stone, James R; Furie, Karen L

    2007-10-01

    The aim of this article is to evaluate 3.0 T magnetic resonance imaging for characterization of vessel morphology and plaque composition. Emphasis is placed on early and moderate stages of carotid atherosclerosis, where increases in signal-to-noise (SNR) and contrast-to-noise (CNR) ratios compared with 1.5 T are sought. Comparison of in vivo 3.0 T imaging to histopathology is performed for validation. Parallel acceleration methods applied with an 8-channel carotid array are investigated as well as higher field ex vivo imaging to explore even further gains. The overall endeavor is to improve prospective assessment of atherosclerosis stage and stability for reduction of atherothrombotic event risk. A total of 10 male and female subjects ranging in age from 22 to 72 years (5 healthy and 5 with cardiovascular disease) participated. Custom-built array coils were used with endogenous and exogenous multicontrast bright and black-blood protocols for 3.0 T carotid imaging. Comparisons were performed to 1.5 T, and ex vivo plaque was stained with hematoxylin and eosin for histology. Imaging (9.4 T) was also performed on intact specimens. The factor of 2 gain in signal-to-noise SNR is realized compared with 1.5 T along with improved wall-lumen and plaque component CNR. Post-contrast black-blood imaging within 5-10 minutes of gadolinium injection is optimal for detection of the necrotic lipid component. In a preliminary 18-month follow-up study, this method provided measurement of a 50% reduction in lipid content with minimal change in plaque size in a subject receiving aggressive statin therapy. Parallel imaging applied with signal averaging further improves 3.0 T black-blood vessel wall imaging. The use of 3.0 T for carotid plaque imaging has demonstrated increases in SNR and CNR compared with 1.5 T. Quantitative prospective studies of moderate and early plaques are feasible at 3.0 T. Continued improvements in coil arrays, 3-dimensional pulse sequences, and the use of novel

  19. BRCA2, EGFR, and NTRK mutations in mismatch repair-deficient colorectal cancers with MSH2 or MLH1 mutations.

    PubMed

    Deihimi, Safoora; Lev, Avital; Slifker, Michael; Shagisultanova, Elena; Xu, Qifang; Jung, Kyungsuk; Vijayvergia, Namrata; Ross, Eric A; Xiu, Joanne; Swensen, Jeffrey; Gatalica, Zoran; Andrake, Mark; Dunbrack, Roland L; El-Deiry, Wafik S

    2017-06-20

    Deficient mismatch repair (MMR) and microsatellite instability (MSI) contribute to ~15% of colorectal cancer (CRCs). We hypothesized MSI leads to mutations in DNA repair proteins including BRCA2 and cancer drivers including EGFR. We analyzed mutations among a discovery cohort of 26 MSI-High (MSI-H) and 558 non-MSI-H CRCs profiled at Caris Life Sciences. Caris-profiled MSI-H CRCs had high mutation rates (50% vs 14% in non-MSI-H, P < 0.0001) in BRCA2. Of 1104 profiled CRCs from a second cohort (COSMIC), MSH2/MLH1-mutant CRCs showed higher mutation rates in BRCA2 compared to non-MSH2/MLH1-mutant tumors (38% vs 6%, P < 0.0000001). BRCA2 mutations in MSH2/MLH1-mutant CRCs included 75 unique mutations not known to occur in breast or pancreatic cancer per COSMIC v73. Only 5 deleterious BRCA2 mutations in CRC were previously reported in the BIC database as germ-line mutations in breast cancer. Some BRCA2 mutations were predicted to disrupt interactions with partner proteins DSS1 and RAD51. Some CRCs harbored multiple BRCA2 mutations. EGFR was mutated in 45.5% of MSH2/MLH1-mutant and 6.5% of non-MSH2/MLH1-mutant tumors (P < 0.0000001). Approximately 15% of EGFR mutations found may be actionable through TKI therapy, including N700D, G719D, T725M, T790M, and E884K. NTRK gene mutations were identified in MSH2/MLH1-mutant CRC including NTRK1 I699V, NTRK2 P716S, and NTRK3 R745L. Our findings have clinical relevance regarding therapeutic targeting of BRCA2 vulnerabilities, EGFR mutations or other identified oncogenic drivers such as NTRK in MSH2/MLH1-mutant CRCs or other tumors with mismatch repair deficiency.

  20. Effects of induction docetaxel, platinum, and fluorouracil chemotherapy in patients with stage III or IVA/B nasopharyngeal cancer treated with concurrent chemoradiation therapy: Final results of 2 parallel phase 2 clinical trials.

    PubMed

    Kong, Lin; Zhang, Youwang; Hu, Chaosu; Guo, Ye; Lu, Jiade J

    2017-06-15

    The effects of docetaxel, platinum, and fluorouracil (TPF) induction chemotherapy plus concurrent chemoradiotherapy (CCRT) on locoregionally advanced nasopharyngeal cancer (NPC) are unclear. This study examined the long-term outcomes of the addition of this regimen to CCRT for stage III and IVA/B NPC. Two parallel, single-arm phase 2 trials were performed synchronously to evaluate the efficacy and toxicity of TPF-based induction chemotherapy in patients with stage III or IVA/B NPC. The induction chemotherapy, which preceded standard intensity-modulated radiation therapy/platinum-based chemoradiation, consisted of 3 cycles of docetaxel (75 mg/m 2 on day 1), cisplatin (75 mg/m 2 on day 1), and a continuous infusion of fluorouracil (500 mg/m 2 /d on days 1-5) every 4 weeks. The primary endpoint for both trials was 5-year overall survival (OS). Between January 2007 and July 2010, 52 eligible patients with stage III NPC and 64 eligible patients with nonmetastatic stage IV NPC were accrued to the 2 trials. With a median follow-up of 67 months, the 5-year OS, progression-free survival, distant metastasis-free survival, and local progression-free survival (LPFS) rates were all improved in comparison with historical benchmarks for patients with stage III or IVA/IVB NPC. Multivariate analyses indicated that T and N classifications (T1/T2 vs T3/T4 and N3 vs N0-N2) were the only significant prognosticators for OS. The number of induction chemotherapy cycles was the only significant prognostic factor for predicting LPFS. TPF-based induction chemotherapy appears to significantly improve outcomes in comparison with historical data when it is administered before CCRT for locoregionally advanced NPC. A phase 3 trial is currently being performed to confirm this benefit. Cancer 2017;123:2258-2267. © 2017 American Cancer Society. © 2017 American Cancer Society.

  1. Induction of protective anti-CTL epitope responses against HER-2-positive breast cancer based on multivalent T7 phage nanoparticles.

    PubMed

    Pouyanfard, Somayeh; Bamdad, Taravat; Hashemi, Hamidreza; Bandehpour, Mojgan; Kazemi, Bahram

    2012-01-01

    We report here the development of multivalent T7 bacteriophage nanoparticles displaying an immunodominant H-2k(d)-restricted CTL epitope derived from the rat HER2/neu oncoprotein. The immunotherapeutic potential of the chimeric T7 nanoparticles as anti-cancer vaccine was investigated in BALB/c mice in an implantable breast tumor model. The results showed that T7 phage nanoparticles confer a high immunogenicity to the HER-2-derived minimal CTL epitope, as shown by inducing robust CTL responses. Furthermore, the chimeric nanoparticles protected mice against HER-2-positive tumor challenge in both prophylactic and therapeutic setting. In conclusion, these results suggest that CTL epitope-carrying T7 phage nanoparticles might be a promising approach for development of T cell epitope-based cancer vaccines.

  2. Induction of Protective Anti-CTL Epitope Responses against HER-2-Positive Breast Cancer Based on Multivalent T7 Phage Nanoparticles

    PubMed Central

    Pouyanfard, Somayeh; Bamdad, Taravat; Hashemi, Hamidreza; Bandehpour, Mojgan; Kazemi, Bahram

    2012-01-01

    We report here the development of multivalent T7 bacteriophage nanoparticles displaying an immunodominant H-2kd-restricted CTL epitope derived from the rat HER2/neu oncoprotein. The immunotherapeutic potential of the chimeric T7 nanoparticles as anti-cancer vaccine was investigated in BALB/c mice in an implantable breast tumor model. The results showed that T7 phage nanoparticles confer a high immunogenicity to the HER-2-derived minimal CTL epitope, as shown by inducing robust CTL responses. Furthermore, the chimeric nanoparticles protected mice against HER-2-positive tumor challenge in both prophylactic and therapeutic setting. In conclusion, these results suggest that CTL epitope-carrying T7 phage nanoparticles might be a promising approach for development of T cell epitope-based cancer vaccines. PMID:23166703

  3. Staging of pelvic lymph nodes in patients with prostate cancer: Usefulness of multiple b value SE-EPI diffusion-weighted imaging on a 3.0 T MR system.

    PubMed

    Vallini, Valentina; Ortori, Simona; Boraschi, Piero; Manassero, Francesca; Gabelloni, Michela; Faggioni, Lorenzo; Selli, Cesare; Bartolozzi, Carlo

    2016-01-01

    To evaluate the usefulness of diffusion-weighted imaging (DWI) with a multiple b value SE-EPI sequence on a 3.0 T MR scanner for staging of pelvic lymph nodes in patients with prostate cancer candidate to radical prostatectomy and extended pelvic lymph node dissection (PLND). Institutional review board approval was obtained and written informed consent was taken from all enrolled subjects. A series of 26 patients with pathologically proven prostate cancer (high or intermediate risk according to D'Amico risk groups) scheduled for radical prostatectomy and PLND underwent 3 T MRI before surgery. DWI was performed using an axial respiratory-triggered spin-echo echo-planar sequence with multiple b values (500, 800, 1000, 1500 s/mm(2)) in all diffusion directions. ADC values were calculated by means of dedicated software fitting the curve obtained from the corresponding ADC for each b value. Fitted ADC measurements were performed at the level of proximal and distal external iliac, internal iliac, and obturator nodal stations bilaterally. Lymph node appearance was also assessed in terms of short axis, long-to-short axis ratio, node contour and intranodal heterogeneity of signal intensity. A total of 173 lymph nodes and 104 nodal stations were evaluated on DWI and pathologically analysed. Mean fitted ADC values were 0.79 ± 0.14 × 10(-3) mm(2)/s for metastatic lymph nodes and 1.13 ± 0.29 × 10(-3) mm(2)/s in non-metastatic ones (P < 0.0001). The cut-off for fitted ADC obtained by ROC curve analysis was 0.91 × 10(-3) mm(2)/s. A two-point-level score was assigned for each qualitative parameter, and the mean grading score was 6.09 ± 0.61 for metastastic lymph nodes and 5.42 ± 0.79 for non-metastatic ones, respectively (P = 0.001). Using a score threshold of 4 for morphological, structural, and dimensional MRI analysis and a cut--off value of 0.91 × 10(-3) mm(2)/s for fitted ADC measurements of pelvic lymph nodes, per--station sensitivity

  4. T2 relaxation time is related to liver fibrosis severity

    PubMed Central

    Siqueira, Luiz; Uppal, Ritika; Alford, Jamu; Fuchs, Bryan C.; Yamada, Suguru; Tanabe, Kenneth; Chung, Raymond T.; Lauwers, Gregory; Chew, Michael L.; Boland, Giles W.; Sahani, Duhyant V.; Vangel, Mark; Hahn, Peter F.; Caravan, Peter

    2016-01-01

    Background The grading of liver fibrosis relies on liver biopsy. Imaging techniques, including elastography and relaxometric, techniques have had varying success in diagnosing moderate fibrosis. The goal of this study was to determine if there is a relationship between the T2-relaxation time of hepatic parenchyma and the histologic grade of liver fibrosis in patients with hepatitis C undergoing both routine, liver MRI and liver biopsy, and to validate our methodology with phantoms and in a rat model of liver fibrosis. Methods This study is composed of three parts: (I) 123 patients who underwent both routine, clinical liver MRI and biopsy within a 6-month period, between July 1999 and January 2010 were enrolled in a retrospective study. MR imaging was performed at 1.5 T using dual-echo turbo-spin echo equivalent pulse sequence. T2 relaxation time of liver parenchyma in patients was calculated by mono-exponential fit of a region of interest (ROI) within the right lobe correlating to histopathologic grading (Ishak 0–6) and routine serum liver inflammation [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)]. Statistical comparison was performed using ordinary logistic and ordinal logistic regression and ANOVA comparing T2 to Ishak fibrosis without and using AST and ALT as covariates; (II) a phantom was prepared using serial dilutions of dextran coated magnetic iron oxide nanoparticles. T2 weighed imaging was performed by comparing a dual echo fast spin echo sequence to a Carr-Purcell-Meigboom-Gill (CPMG) multi-echo sequence at 1.5 T. Statistical comparison was performed using a paired t-test; (III) male Wistar rats receiving weekly intraperitoneal injections of phosphate buffer solution (PBS) control (n=4 rats); diethylnitrosamine (DEN) for either 5 (n=5 rats) or 8 weeks (n=4 rats) were MR imaged on a Bruker Pharmascan 4.7 T magnet with a home-built bird-cage coil. T2 was quantified by using a mono-exponential fitting algorithm on multi-slice multi

  5. Postoperative Radiotherapy for Pathologic N2 Non–Small-Cell Lung Cancer Treated With Adjuvant Chemotherapy: A Review of the National Cancer Data Base

    PubMed Central

    Robinson, Cliff G.; Patel, Aalok P.; Bradley, Jeffrey D.; DeWees, Todd; Waqar, Saiama N.; Morgensztern, Daniel; Baggstrom, Maria Q.; Govindan, Ramaswamy; Bell, Jennifer M.; Guthrie, Tracey J.; Colditz, Graham A.; Crabtree, Traves D.; Kreisel, Daniel; Krupnick, Alexander S.; Patterson, G. Alexander; Meyers, Bryan F.; Puri, Varun

    2015-01-01

    Purpose To investigate the impact of modern postoperative radiotherapy (PORT) on overall survival (OS) for patients with N2 non–small-cell lung cancer (NSCLC) treated nationally with surgery and adjuvant chemotherapy. Patients and Methods Patients with pathologic N2 NSCLC who underwent complete resection and adjuvant chemotherapy from 2006 to 2010 were identified from the National Cancer Data Base and stratified by use of PORT (≥ 45 Gy). A total of 4,483 patients were identified (PORT, n = 1,850; no PORT, n = 2,633). The impact of patient and treatment variables on OS was explored using Cox regression. Results Median follow-up time was 22 months. On univariable analysis, improved OS correlated with younger age, treatment at an academic facility, female sex, urban population, higher income, lower Charlson comorbidity score, smaller tumor size, multiagent chemotherapy, resection with at least a lobectomy, and PORT. On multivariable analysis, improved OS remained independently predicted by younger age, female sex, urban population, lower Charlson score, smaller tumor size, multiagent chemotherapy, resection with at least a lobectomy, and PORT (hazard ratio, 0.886; 95% CI, 0.798 to 0.988). Use of PORT was associated with an increase in median and 5-year OS compared with no PORT (median OS, 45.2 v 40.7 months, respectively; 5-year OS, 39.3% [95% CI, 35.4% to 43.5%] v 34.8% [95% CI, 31.6% to 38.3%], respectively; P = .014). Conclusion For patients with N2 NSCLC after complete resection and adjuvant chemotherapy, modern PORT seems to confer an additional OS advantage beyond that achieved with adjuvant chemotherapy alone. PMID:25667283

  6. Effect of ZnO Nanoparticles on the Sintering Behavior and Physical Properties of Bi0.5(Na0.8K0.2)0.5TiO3 Lead-Free Ceramics

    NASA Astrophysics Data System (ADS)

    Vuong, Le Dai; Truong-Tho, Nguyen

    2017-11-01

    Sintered Bi0.5(Na0.8K0.2)0.5TiO3 + x wt.% ZnO nanoparticle (BNKT- xZnOn) ceramics have been fabricated by conventional annealing with the aid of ultrasound waves for preliminary milling. Because of the presence of the liquid Bi2O3-ZnO phase at the eutectic point of 738°C, the sintering temperature decreased from 1150°C to 1000°C, and the morphology phase boundary of BNKT- xZnOn ceramics can be clarified by two separated peaks at (002)T and (200)T of 2 θ in the x-ray diffraction (XRD) patterns. The improvement of ferroelectric properties has been obtained for BNZT-0.2 wt.% ZnOn ceramics by the increase of remanent polarization up to 20.4 μC/cm2 and a decrease of electric coercive field down to 14.2 kV/cm. The piezoelectric parameters of the ceramic included a piezoelectric charge constant of d 31 = 78 pC/N; electromechanical coupling factors k p = 0.31 and k t = 0.34, larger than the values of 42 pC/N, 0.12 and 0.13, respectively, were obtained for the BNKT ceramics.

  7. CHEK2 mutation and risk of prostate cancer: a systematic review and meta-analysis

    PubMed Central

    Wang, Yue; Dai, Bo; Ye, Dingwei

    2015-01-01

    Background: CHEK2 encodes for a G2 checkpoint kinase which plays a critical role in DNA repair. Its mutation confers an increased risk of breast cancer. It has also been suggested to increase risks of prostate cancer, but its involvement with this type of cancer has not been confirmed. Methods: We performed a systematic review and meta-analysis to clarify the association between CHEK2 1100delC, IVS2+1G>A, I157T mutation and risk of Prostate Cancer. A comprehensive, computerized literature search of PubMed until December 27, 2014 was carried out. Eligible studies were included according to specific inclusion criteria. Pooled hazard ratio was estimated using the fixed effects model or random effects model according to heterogeneity between studies. Results: Eight eligible studies were included in the analysis, all were retrospective studies. The overall meta-analysis demonstrated that the CHEK2 1100delC mutation (OR 3.29; 95% confidence interval: 1.85-5.85; P = 0.00) and I157T missense mutation (OR 1.80; 95% confidence interval: 1.51-2.14; P = 0.00) was associated with higher risk of Prostate Cancer, and CHEK2 1100delC mutation is irrelevant to familial aggregation phenomenon of prostate cancer (OR 1.59; 95% confidence interval: 0.79-3.20; P = 0.20). The IVS2+1G>A mutation is also irrelevant to Prostate Cancer (OR = 1.59, 95% CI = 0.93-2.71, P = 0.09). None of the single studies materially altered the original results and no evidence of publication bias was found. Conclusion: CHEK2 1100delC mutation and I157T missense mutation in males indicates higher risk of Prostate Cancer, but there’s no evidence to prove the CHEK2 1100delC mutation was associated with Familial prostate cancer. PMID:26629066

  8. CHEK2 mutation and risk of prostate cancer: a systematic review and meta-analysis.

    PubMed

    Wang, Yue; Dai, Bo; Ye, Dingwei

    2015-01-01

    CHEK2 encodes for a G2 checkpoint kinase which plays a critical role in DNA repair. Its mutation confers an increased risk of breast cancer. It has also been suggested to increase risks of prostate cancer, but its involvement with this type of cancer has not been confirmed. We performed a systematic review and meta-analysis to clarify the association between CHEK2 1100delC, IVS2+1G>A, I157T mutation and risk of Prostate Cancer. A comprehensive, computerized literature search of PubMed until December 27, 2014 was carried out. Eligible studies were included according to specific inclusion criteria. Pooled hazard ratio was estimated using the fixed effects model or random effects model according to heterogeneity between studies. Eight eligible studies were included in the analysis, all were retrospective studies. The overall meta-analysis demonstrated that the CHEK2 1100delC mutation (OR 3.29; 95% confidence interval: 1.85-5.85; P = 0.00) and I157T missense mutation (OR 1.80; 95% confidence interval: 1.51-2.14; P = 0.00) was associated with higher risk of Prostate Cancer, and CHEK2 1100delC mutation is irrelevant to familial aggregation phenomenon of prostate cancer (OR 1.59; 95% confidence interval: 0.79-3.20; P = 0.20). The IVS2+1G>A mutation is also irrelevant to Prostate Cancer (OR = 1.59, 95% CI = 0.93-2.71, P = 0.09). None of the single studies materially altered the original results and no evidence of publication bias was found. CHEK2 1100delC mutation and I157T missense mutation in males indicates higher risk of Prostate Cancer, but there's no evidence to prove the CHEK2 1100delC mutation was associated with Familial prostate cancer.

  9. Occurrence of lymph node metastasis in early-stage parotid gland cancer.

    PubMed

    Stenner, Markus; Molls, Christoph; Luers, Jan C; Beutner, Dirk; Klussmann, Jens P; Huettenbrink, Karl-Bernd

    2012-02-01

    Lymph node metastasis is one of the most important factors in therapy and prognosis for patients with parotid gland cancer. Nevertheless, the extent of the primary tumor resection and the necessity of a neck dissection still is a common issue. Since little is known about lymph node metastasis in early-stage parotid gland cancer, the purpose of the present study was to evaluate the occurrence of lymph node metastases in T1 and T2 carcinomas and its impact on local control and survival. We retrospectively analyzed 70 patients with early-stage (T1 and T2) primary parotid gland cancer. All patients were treated with parotidectomy and an ipsilateral neck dissection from 1987 to 2009. Clinicopathological and survival parameters were calculated. The median follow-up time was 51.7 months. A positive pathological lymph node stage (pN+) was found in 21.4% of patients with a significant correlation to the clinical lymph node stage (cN) (p = 0.061). There were no differences in the clinical and histopathological data between pN- and pN+ patients. In 73.3% of pN+ patients, the metastases were located intraparotideal. The incidence of occult metastases (pN+/cN-) was 17.2%. Of all patients with occult metastases, 30.0% had extraparotideal lymphatic spread. A positive lymph node stage significantly indicated a poorer 5-year overall as well as 5-year disease-free survival rate compared to pN- patients (p = 0.048; p = 0.011). We propose total parotidectomy in combination with at least a level II-III selective neck dissection in any case of early-stage parotid gland cancer.

  10. Tribody [(HER2)2xCD16] Is More Effective Than Trastuzumab in Enhancing γδ T Cell and Natural Killer Cell Cytotoxicity Against HER2-Expressing Cancer Cells.

    PubMed

    Oberg, Hans H; Kellner, Christian; Gonnermann, Daniel; Sebens, Susanne; Bauerschlag, Dirk; Gramatzki, Martin; Kabelitz, Dieter; Peipp, Matthias; Wesch, Daniela

    2018-01-01

    An enhanced expression of human epidermal growth factor receptor 2 (HER2, ErbB2) often occurs in an advanced stage of breast, ovarian, gastric or esophageal cancer, and pancreatic ductal adenocarcinoma (PDAC). Commonly, HER2 expression is associated with poor clinical outcome or chemoresistance in ovarian and breast cancer patients. Treatment with humanized anti-HER2 monoclonal antibodies, such as trastuzumab or pertuzumab, has improved the outcome of patients with HER2-positive metastatic gastric or breast cancer, but not all patients benefit. In this study, the bispecific antibody [(HER2) 2 xCD16] in the tribody format was employed to re-direct CD16-expressing γδ T lymphocytes as well as natural killer (NK) cells to the tumor-associated cell surface antigen HER2 to enhance their cytotoxic anti-tumor activity. Tribody [(HER2) 2 xCD16] comprises two HER2-specific single chain fragment variable fused to a fragment antigen binding directed to the CD16 (FcγRIII) antigen expressed on γδ T cells and NK cells. Our results revealed the superiority of tribody [(HER2) 2 xCD16] compared to trastuzumab in triggering γδ T cell and NK cell-mediated lysis of HER2-expressing tumor cells, such as PDAC, breast cancer, and autologous primary ovarian tumors. The increased efficacy of [(HER2) 2 xCD16] can be explained by an enhanced degranulation of immune cells. Although CD16 expression was decreased on γδ T cells in several PDAC patients and the number of tumor-infiltrating NK cells and γδ T cells was impaired in ovarian cancer patients, [(HER2) 2 xCD16] selectively enhanced cytotoxicity of cells from these patients. Here, unique anti-tumor properties of tribody [(HER2) 2 xCD16] are identified which beyond addressing HER2 overexpressing solid tumors may allow to treat with similar immunoconstructs combined with the adoptive transfer of γδ T cells and NK cells refractory hematological malignancies. A major advantage of γδ T cells and NK cells in the transplant

  11. Tribody [(HER2)2xCD16] Is More Effective Than Trastuzumab in Enhancing γδ T Cell and Natural Killer Cell Cytotoxicity Against HER2-Expressing Cancer Cells

    PubMed Central

    Oberg, Hans H.; Kellner, Christian; Gonnermann, Daniel; Sebens, Susanne; Bauerschlag, Dirk; Gramatzki, Martin; Kabelitz, Dieter; Peipp, Matthias; Wesch, Daniela

    2018-01-01

    An enhanced expression of human epidermal growth factor receptor 2 (HER2, ErbB2) often occurs in an advanced stage of breast, ovarian, gastric or esophageal cancer, and pancreatic ductal adenocarcinoma (PDAC). Commonly, HER2 expression is associated with poor clinical outcome or chemoresistance in ovarian and breast cancer patients. Treatment with humanized anti-HER2 monoclonal antibodies, such as trastuzumab or pertuzumab, has improved the outcome of patients with HER2-positive metastatic gastric or breast cancer, but not all patients benefit. In this study, the bispecific antibody [(HER2)2xCD16] in the tribody format was employed to re-direct CD16-expressing γδ T lymphocytes as well as natural killer (NK) cells to the tumor-associated cell surface antigen HER2 to enhance their cytotoxic anti-tumor activity. Tribody [(HER2)2xCD16] comprises two HER2-specific single chain fragment variable fused to a fragment antigen binding directed to the CD16 (FcγRIII) antigen expressed on γδ T cells and NK cells. Our results revealed the superiority of tribody [(HER2)2xCD16] compared to trastuzumab in triggering γδ T cell and NK cell-mediated lysis of HER2-expressing tumor cells, such as PDAC, breast cancer, and autologous primary ovarian tumors. The increased efficacy of [(HER2)2xCD16] can be explained by an enhanced degranulation of immune cells. Although CD16 expression was decreased on γδ T cells in several PDAC patients and the number of tumor-infiltrating NK cells and γδ T cells was impaired in ovarian cancer patients, [(HER2)2xCD16] selectively enhanced cytotoxicity of cells from these patients. Here, unique anti-tumor properties of tribody [(HER2)2xCD16] are identified which beyond addressing HER2 overexpressing solid tumors may allow to treat with similar immunoconstructs combined with the adoptive transfer of γδ T cells and NK cells refractory hematological malignancies. A major advantage of γδ T cells and NK cells in the transplant situation of

  12. Identification of an N staging system that predicts oncologic outcome in resected left-sided pancreatic cancer.

    PubMed

    Kim, Sung Hyun; Hwang, Ho Kyoung; Lee, Woo Jung; Kang, Chang Moo

    2016-06-01

    In this study, we investigated which N staging system was the most accurate at predicting survival in pancreatic cancer patients.Lymph node (LN) metastasis is known to be one of the important prognostic factors in resected pancreatic cancer. There are several LN evaluation systems to predict oncologic impact.From January 1992 to December 2014, 77 medical records of patients who underwent radical pancreatectomy for left-sided pancreatic cancer were reviewed retrospectively. Clinicopathologic variables including pN stage, total number of retrieved LNs (N-RLN), lymph node ratio (LNR), and absolute number of LN metastases (N-LNmet) were evaluated. Disease-free survival (DFS) and disease-specific survival (DSS) were analyzed according to these 4 LN staging systems.In univariate analysis, pN stage (pN0 vs pN1: 17.5 months vs 7.9 months, P = 0.001), LNR (<0.08 vs ≥0.08: 17.5 months vs 4.4 months, P < 0.001), and N-LNmet (#N = 0 vs #N = 1 vs #N≥2: 17.5 months vs 11.0 months vs 6.4 months, P = 0.002) had a significant effect on DFS, whereas the pN stage (pN0 vs pN1: 35.3 months vs 16.7 months, P = 0.001), LNR (<0.08 vs ≥0.08: 37.1 months vs 15.0 months, P < 0.001), and N-LNmet (#N = 0 vs #N = 1 vs #N≥2: 35.3 months vs 18.4 months vs 16.4 months, P = 0.001) had a significant effect on DSS. In multivariate analysis, N-LNmet (#N≥2) was identified as an independent prognostic factor of oncologic outcome (DFS and DSS: Exp (β) = 2.83, P = 0.001, and Exp (β) = 3.17, P = 0.001, respectively).Absolute number of lymph node metastases predicted oncologic outcome in resected left-sided pancreatic cancer patients.

  13. The thermodynamic properties of 2-ethylhexyl acrylate over the temperature range from T0 to 350 K

    NASA Astrophysics Data System (ADS)

    Kulagina, T. G.; Samosudova, Ya. S.; Letyanina, I. A.; Sevast'yanov, E. V.; Smirnova, N. N.; Smirnova, L. A.; Mochalova, A. E.

    2012-05-01

    The temperature dependence of the heat capacity C {/p o}= f( T) 2 of 2-ethylhexyl acrylate was studied in an adiabatic vacuum calorimeter over the temperature range 6-350 K. Measurement errors were mainly of 0.2%. Glass formation and vitreous state parameters were determined. An isothermic shell calorimeter with a static bomb was used to measure the energy of combustion of 2-ethylhexyl acrylate. The experimental data were used to calculate the standard thermodynamic functions C {/p o}( T), H o( T)- H o(0), S o( T)- S o(0), and G o( T)- H o(0) of the compound in the vitreous and liquid states over the temperature range from T0 to 350 K, the standard enthalpies of combustion Δc H o, and the thermodynamic characteristics of formation Δf H o, Δf S o, and Δf G o at 298.15 K and p = 0.1 MPa.

  14. Temperature dependence of partial conductivities of the BaZr0.7Ce0.2Y0.1O3-δ proton conductor

    NASA Astrophysics Data System (ADS)

    Heras-Juaristi, Gemma; Pérez-Coll, Domingo; Mather, Glenn C.

    2017-10-01

    Partial conductivities are presented for BaZr0.7Ce0.2Y0.1O3-δ, an important proton conductor for protonic-ceramic fuel cells and membrane reactors. Atmospheric dependencies of impedance performed in humidified and dry O2, air, N2 and H2(10%)/N2(90%) in the temperature range 300-900 °C, supported by the modified emf method, confirm significant electron-hole and protonic contributions to transport. For very reducing and wet atmospheres, the conductivity is predominantly ionic, with a higher participation of protons with decreasing temperature and increasing water-vapour partial pressure (pH2O). From moderately reducing conditions of wet N2 to wet O2, however, the conductivity is considerably influenced by electron holes as revealed by a significant dependence of total conductivity on oxygen partial pressure (pO2). With higher pH2O, proton transport increases, with a concomitant decrease of holes and oxygen vacancies. However, the effect of pH2O is also influenced by temperature, with a greater protonic contribution at both lower temperature and pO2. Values of proton transport number tH ≈ 0.63 and electronic transport number th ≈ 0.37 are obtained at 600 °C for pH2O = 0.022 atm and pO2 = 0.2 atm, whereas tH ≈ 0.95 and th ≈ 0.05 for pO2 = 10-5 atm. A hydration enthalpy of -109 kJ mol-1 is obtained in the range 600-900 °C.

  15. [Genotyping of BRCA1, BRCA2 and CHEK2 germline mutations in Russian breast cancer patients using diagnostic biochips].

    PubMed

    Nasedkina, T V; Gromyko, O E; Emel'ianova, M A; Ignatova, E O; Kazubskaia, T P; Portnoĭ, S M; Zasedatelev, A S; Liubchenko, L N

    2014-01-01

    Germline mutations of BRCA1/2 genes cause the predisposition of their carriers to breast or/and ovary cancers (BC or/and OC) during the lifetime. Identification of these mutations is a basis of molecular diagnosis for BC susceptibility. Rapid genotyping technique using microarrays for identification of BRCA1 185delAG, 300T>G, 4153delA, 5382insC mutations and 4158 A>G sequence variant; BRCA2 695insT and 6174delT mutations; 1100delC mutation in CHEK2 gene was applied for 412 randomly collected breast cancer samples from the central region of European area of Russia. In 25 (6.0%) patients (6.0%) BC was associated with other tumours: OC, cervical cancer, colorectal cancer etc. BRCA1/2 and CHEK2 mutations were found in 33 (8.0%) BC patients. The most frequent mutation was BRCA1 5382insC, occurred in 16 (3.9%) BC patients, and CHEK2 1100delC, revealed in 7 (1.7%) BC patients. An application of diagnostic BC-microarray for genetic testing of BRCA1/2 and CHEK2 founder mutations has been discussed.

  16. Colorectal cancer in patients with type 2 diabetes mellitus: a single-center experience.

    PubMed

    Sinagra, E; Guarnotta, V; Raimondo, D; Mocciaro, F; Dolcimascolo, S; Rizzolo, C A; Puccia, F; Maltese, N; Citarrella, R; Messina, M; Spada, M; Tomasello, G; Cappello, F; Leone, A; Rossi, F; Di Mitri, R; Morreale, G C; Marasà, S; Midiri, M; Midiri, F; Sinagra, D

    2017-01-01

    Type 2 diabetes mellitus (T2DM) is associated with an increased risk of colorectal cancer (CRC). The aim of the study is to evaluate the prevalence of CRC in a cohort of Caucasian patients with T2DM and the association with other variables previously known to be related with increased risk of CRC. We retrospectively evaluated the data of 741 consecutive Caucasian patients with T2DM who underwent colonoscopic screening in our tertiary referral center. A control cohort of 333 patients with thyroid disease was selected to evaluate the difference in the incidence of CRC. At a median follow-up of 132.5 months (range 33.3-175.7), 67 cases of cancer (prevalence 9%) occurred; among these, 14 cases of CRC were reported (prevalence 1.88%) among the diabetic patients, while only two case (one of these was a CRC) (overall prevalence 0.006%, prevalence of CRC 0.003%) occurred in the control group; the difference between the prevalence of CRC was statistically significant (chi-square 4.21, p=0.04). The median duration of T2DM to CRC diagnosis was 168 months (range 12-768). At the univariate analysis, older age (p=0.001, r 0.138) and diabetes duration (p=0.001, r 0.138) were related to higher risk of cancer, while metformin seems to be protective towards cancer (p=0.07, r -0.098). In the subset of patients with CRC, the age (RR = 2.25; 95% CI: 0.30 - 17.31; p less than 0.001), the diabetes duration (RR = 1.93; 95% CI: 0.25 – 14.77; p = 0.001) and the sulphonylureas treatment (RR = 2.33; 95% CI: 0.78 – 7.38; p = 0.007) were independently correlated with CRC. In our study, the prevalence of CRC in the cohort of patients with T2DM was higher compared to that from the National Tumor Register in 2010 (0.5%). Furthermore, we could speculate that sulphonylureas may play a role in CRC carcinogenesis impairing the physiological insulin secretion.

  17. Usefulness of IDEAL T2 imaging for homogeneous fat suppression and reducing susceptibility artefacts in brachial plexus MRI at 3.0 T.

    PubMed

    Tagliafico, Alberto; Bignotti, Bianca; Tagliafico, Giulio; Martinoli, Carlo

    2016-01-01

    To quantitatively and qualitatively compare fat-suppressed MR imaging quality using iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) with that using frequency-selective fat-suppressed (FSFS) T2 images of the brachial plexus at 3.0 T. Prospective MR image analysis was performed in 40 volunteers and 40 patients at a single centre. Oblique-sagittal and coronal IDEAL fat-suppressed T2 images and FSFS T2 images were compared. Visual assessment was performed by two independent musculoskeletal radiologists with respect to: (1) susceptibility artefacts around the neck, (2) homogeneity of fat suppression, (3) image sharpness and (4) tissue resolution contrast of pathologies. The signal-to-noise ratios (SNR) for each image sequence were assessed. Compared to FSFS sequences, IDEAL fat-suppressed T2 images significantly reduced artefacts around the brachial plexus and significantly improved homogeneous fat suppression (p < 0.05). IDEAL significantly improved sharpness and lesion-to-tissue contrast (p < 0.05). The mean SNRs were significantly improved on T2-weighted IDEAL images (p < 0.05). IDEAL technique improved image quality by reducing artefacts around the brachial plexus while maintaining a high SNR and provided superior homogeneous fat suppression than FSFS sequences.

  18. Iyengar-Yoga Compared to Exercise as a Therapeutic Intervention during (Neo)adjuvant Therapy in Women with Stage I-III Breast Cancer: Health-Related Quality of Life, Mindfulness, Spirituality, Life Satisfaction, and Cancer-Related Fatigue.

    PubMed

    Lötzke, Désirée; Wiedemann, Florian; Rodrigues Recchia, Daniela; Ostermann, Thomas; Sattler, Daniel; Ettl, Johannes; Kiechle, Marion; Büssing, Arndt

    2016-01-01

    This study aims to test the effects of yoga on health-related quality of life, life satisfaction, cancer-related fatigue, mindfulness, and spirituality compared to conventional therapeutic exercises during (neo)adjuvant cytotoxic and endocrine therapy in women with breast cancer. In a randomized controlled trial 92 women with breast cancer undergoing oncological treatment were randomly enrolled for a yoga intervention (YI) (n = 45) or for a physical exercise intervention (PEI) (n = 47). Measurements were obtained before (t 0) and after the intervention (t 1) as well as 3 months after finishing intervention (t 2) using standardized questionnaires. Life satisfaction and fatigue improved under PEI (p < 0.05) but not under YI (t 0 to t 2). Regarding quality of life (EORTC QLQ-C30) a direct effect (t 0 to t 1; p < 0.001) of YI was found on role and emotional functioning, while under PEI only emotional functioning improved. Significant improvements (p < 0.001) were observed at both t 1 and t 2 also for symptom scales in both groups: dyspnea, appetite loss, constipation, and diarrhea. There was no significant difference between therapies for none of the analyzed variables neither for t 1 nor for t 2. During chemotherapy, yoga was not seen as more helpful than conventional therapeutic exercises. This does not argue against its use in the recovery phase.

  19. Iyengar-Yoga Compared to Exercise as a Therapeutic Intervention during (Neo)adjuvant Therapy in Women with Stage I–III Breast Cancer: Health-Related Quality of Life, Mindfulness, Spirituality, Life Satisfaction, and Cancer-Related Fatigue

    PubMed Central

    Lötzke, Désirée; Wiedemann, Florian; Rodrigues Recchia, Daniela; Ostermann, Thomas; Sattler, Daniel; Ettl, Johannes; Kiechle, Marion; Büssing, Arndt

    2016-01-01

    This study aims to test the effects of yoga on health-related quality of life, life satisfaction, cancer-related fatigue, mindfulness, and spirituality compared to conventional therapeutic exercises during (neo)adjuvant cytotoxic and endocrine therapy in women with breast cancer. In a randomized controlled trial 92 women with breast cancer undergoing oncological treatment were randomly enrolled for a yoga intervention (YI) (n = 45) or for a physical exercise intervention (PEI) (n = 47). Measurements were obtained before (t 0) and after the intervention (t 1) as well as 3 months after finishing intervention (t 2) using standardized questionnaires. Life satisfaction and fatigue improved under PEI (p < 0.05) but not under YI (t 0 to t 2). Regarding quality of life (EORTC QLQ-C30) a direct effect (t 0 to t 1; p < 0.001) of YI was found on role and emotional functioning, while under PEI only emotional functioning improved. Significant improvements (p < 0.001) were observed at both t 1 and t 2 also for symptom scales in both groups: dyspnea, appetite loss, constipation, and diarrhea. There was no significant difference between therapies for none of the analyzed variables neither for t 1 nor for t 2. During chemotherapy, yoga was not seen as more helpful than conventional therapeutic exercises. This does not argue against its use in the recovery phase. PMID:27019663

  20. Locoregional outcomes in clinical stage IIB breast cancer after neoadjuvant therapy and mastectomy with or without radiation.

    PubMed

    Diaz, Dayssy A; Hurley, Judith; Reis, Isildinha; Takita, Cristiane; Zhao, Wei; Wright, Jean

    2014-12-01

    Low rates of locoregional recurrence (LRR) in patients with clinical stage IIB breast cancer (cT2N1 or cT3N0) who undergo neoadjuvant therapy (NAT) and mastectomy have been reported. We aimed to quantify the risk of LRR and the relationship between LRR and potential risk factors in this subset of patients. We conducted a retrospective review of 116 patients with clinical IIB breast cancer who underwent NAT followed by mastectomy +/- postmastectomy radiotherapy (PMRT) between 2000 and 2009. We estimated the rate of LRR by cumulative incidence. The effect of prognostic factors was examined by Gray's test and Fine and Gray's test. Median follow-up: 63 months. Median age: 49. 28.4% cT2N1 and 71.6% cT3N0. 62.1% of tumors were ER+, 22.6% HER2+, 19% triple negative (TN). All patients underwent NAT and mastectomy. The majority of patients (87%) received PMRT; 32.3% were treated to chest wall (CW) only, and 67.7% to CW plus supraclavicular (SCV) field. Compared to cT2N1, patients with cT3N0 disease were more likely to be pN0 (60% vs 27%, P = 0.005). There was no significant relationship between risk of LRR and pathologic complete response (pCR), use of PMRT, RT to SCV field, or TN status, but there was higher risk of LRR in cT2N1 than cT3N0 (HR 6.03, P = 0.015). LRR was more common in cT2N1 than in cT3N0 disease, emphasizing the negative prognostic implication of clinically node-positive presentation.

  1. KP-CoT-23 (CCDC83) is a novel immunogenic cancer/testis antigen in colon cancer.

    PubMed

    Song, Myung-Ha; Ha, Jin-Mok; Shin, Dong-Hoon; Lee, Chang-Hun; Old, Lloyd; Lee, Sang-Yull

    2012-11-01

    Cancer/testis (CT) antigens are considered target molecules for cancer immunotherapy. To identify novel CT antigens, immunoscreening of a testicular cDNA library was performed using serum obtained from a colon cancer patient who was immunized with a new dendritic cell vaccine. We isolated 64 positive cDNA clones comprised of 40 different genes, designated KP-CoT-1 through KP-CoT-40. Three of these putative antigens, including KP-CoT-23 (CCDC83), had testis-specific expression profiles in the Unigene database. RT-PCR analysis showed that the expression of 2 KP-Cot-23 variants was restricted to the testis in normal adult tissues. In addition, KP-CoT-23 variants were frequently expressed in a variety of tumors and cancer cell lines, including colon cancer. A serological western blot assay showed IgG antibodies to the KP-CoT-23 protein in 26 of 37 colon cancer patients and in 4 of 21 healthy patients. These data suggest that KP-CoT-23 is a novel CT antigen that may be useful for the diagnosis and immunotherapy of cancer.

  2. Structural, Electronic, and Thermodynamic Properties of Tetragonal t-SixGe3−xN4

    PubMed Central

    Han, Chenxi; Chai, Changchun; Fan, Qingyang; Yang, Jionghao; Yang, Yintang

    2018-01-01

    The structural, mechanical, anisotropic, electronic, and thermal properties of t-Si3N4, t-Si2GeN4, t-SiGe2N4, and t-Ge3N4 in the tetragonal phase are systematically investigated in the present work. The mechanical stability is proved by the elastic constants of t-Si3N4, t-Si2GeN4, t-SiGe2N4, and t-Ge3N4. Moreover, they all demonstrate brittleness, because B/G < 1.75, and v < 0.26. The elastic anisotropy of t-Si3N4, t-Si2GeN4, t-SiGe2N4, and t-Ge3N4 is characterized by Poisson’s ratio, Young’s modulus, the percentage of elastic anisotropy for bulk modulus AB, the percentage of elastic anisotropy for shear modulus AG, and the universal anisotropic index AU. The electronic structures of t-Si3N4, t-Si2GeN4, t-SiGe2N4, and t-Ge3N4 are all wide band gap semiconductor materials, with band gaps of 4.26 eV, 3.94 eV, 3.83 eV, and 3.25 eV, respectively, when using the Heyd-Scuseria-Ernzerhof (HSE06) hybrid functional. Moreover, t-Ge3N4 is a quasi-direct gap semiconductor material. The thermodynamic properties of t-Si3N4, t-Si2GeN4, t-SiGe2N4, and t-Ge3N4 are investigated utilizing the quasi-harmonic Debye model. The effects of temperature and pressure on the thermal expansion coefficient, heat capacity, Debye temperature, and Grüneisen parameters are discussed in detail. PMID:29518943

  3. Antigen-Specific CD8 Lytic Phenotype Induced by Sipuleucel-T in Hormone-Sensitive or Castration-Resistant Prostate Cancer and Association With Overall Survival.

    PubMed

    Antonarakis, Emmanuel S; Small, Eric J; Petrylak, Daniel; Quinn, David I; Kibel, Adam S; Chang, Nancy; Dearstyne, Erica; Harmon, Matthew; Campogan, Dwayne; Haynes, Heather; Vu, Tuyen; Sheikh, Nadeem A; Drake, Charles G

    2018-06-01

    Sipuleucel-T is FDA-approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC) based on the IMPACT trial showing a 4.1-month benefit in median overall survival (OS) for patients receiving sipuleucel-T vs control. Although efficacy of sipuleucel-T is well-established, its mechanism remains incompletely understood. Patient samples from three sipuleucel-T trials were assessed for peripheral cellular immune responses to the immunogen PA2024 and the target antigen prostatic acid phosphatase (PAP). PAP- and PA2024-specific proliferative and cytolytic responses were characterized to delineate sipuleucel-T-induced immune responses. To quantify potential cytotoxic T lymphocyte (CTL) activity, cell-surface CD107a expression on PAP- or PA2024-specific CD8+ T cells was measured in sipuleucel-T-treated patient and healthy volunteer samples. Increased PA2024-specific CD4+ (p=0.030) and CD8+ (p=0.052) T-cell proliferation from baseline to week 6 was observed (N=14) post-sipuleucel-T, with greater magnitude of PA2024-specific responses compared to PAP. PAP- and PA2024-CTL activity (CD107a positivity) significantly increased at weeks 6 and 26 after sipuleucel-T treatment (p<0.0001; N=22). At 26 weeks post-sipuleucel-T, OS correlated with the magnitude of PAP (Pearson's R, 0.52; p=0.013) or PA2024 (Pearson's R, 0.67; p=0.0006) CTL activity. Higher PA2024-CTL activity at week 26 was significantly associated with longer OS using tertile analysis (p=0.0005; N=22), with PA2024 responses correlating with PAP responses at week 26 (R=0.90; p=1.53E -08 ). This study is the first to report PAP-specific CD8+ T-cell responses elicited by sipuleucel-T treatment. Increased and persistent potential PA2024-specific CTL activity correlated with PAP-specific CTL activity and associated with improved OS following sipuleucel-T treatment. Copyright ©2018, American Association for Cancer Research.

  4. Shoulder impairment before breast cancer surgery.

    PubMed

    Flores, Ann Marie; Dwyer, Kathleen

    2014-09-01

    To compare pre- and post-operative shoulder active range of motion (AROM) values from female breast cancer survivors to population norm values for shoulder AROM; and to compare shoulder AROM differences pre- and post-surgery between female African American and White breast cancer survivors (BCA). This pilot study used a convenience sample and longitudinal design measuring participants 2 times (T0 = baseline, after biopsy but within 2 weeks before BCA surgery; T1 = 2 nd postoperative week). The U.S. has the largest BCA survivor population in history and yet the mortality burden remains highest among AA BCA survivors. AAs may also have greater burden of physical and functional side effects compared to whites and the general population. The data were collected from a convenience sample (n = 33; n AA = 9, n W = 24) and included data on shoulder AROM, medical chart review for pre- and co-morbid conditions, and self-reported demographics and medical history. We used t-tests to compare sample AROM means to population norms. We then compared our sample across 2 timepoints (T0 = pre-surgery; T1 = 2 weeks post-surgery) using independent samples t-tests and repeated measures analysis of variance (p < .05) to compare AA to White sub-samples AROM means. African Americans had significantly less shoulder abduction (at T0) and flexion (at T1) than whites. However, 100% had significantly reduced AROM for all movements at T0 (prior to surgery but after biopsy) when compared to population norms. The significant reduction in shoulder AROM after biopsy but before surgery points to a possible unmet need for early physical therapy intervention. Further research using randomized controlled trial design is recommended.

  5. Tumor-Infiltrating T Cells and the PD-1 Checkpoint Pathway in Advanced Differentiated and Anaplastic Thyroid Cancer

    PubMed Central

    Bastman, Jill J.; Serracino, Hilary S.; Zhu, Yuwen; Koenig, Michelle R.; Mateescu, Valerica; Sams, Sharon B.; Davies, Kurtis D.; Raeburn, Christopher D.; McIntyre, Robert C.; Haugen, Bryan R.

    2016-01-01

    Context: Five to 10% of patients with differentiated thyroid cancers (DTC) develop invasive and/or distant metastatic disease that is marginally improved with standard therapies. Prognosis is poor for patients with anaplastic thyroid cancer, with a median survival of 3–5 months. We suggest that a paradigm shift is necessary in the treatment of advanced cases. Objective: We hypothesized that a T-cell response is generated in advanced thyroid cancer and may be a viable therapeutic target. Design: Primary DTCs were analyzed by quantitative RT-PCR (n = 92) for expression of CD3, CD8, forkhead box (Fox)-P3, programmed death (PD)-1, PD-1 ligand-1, and PD-1 ligand-2 and biopsied for cellular analysis by flow cytometry (n = 11). Advanced pT4 cases (n = 22) and metastases (n = 5) were analyzed by immunohistochemistry. Setting: The study was conducted at the University of Colorado Hospital. Patients: Thyroid cancer patients undergoing thyroidectomy or completion surgery for advanced disease between 2002 and 2013 participated in the study. Intervention: There were no interventions. Main Outcome Measure: Immune markers were analyzed for association with disease severity. Results: Immune markers were commonly expressed at the RNA level. PD-L1 was higher (P = .0443) in patients with nodal metastases. FoxP3+ (P < .0001), PD-1+CD8+ (P = .0058), and PD-1+CD4+ (P = .0104) T cells were enriched in DTC biopsies. CD8+ and FoxP3+ T cells were detected by immunohistochemistry in all pT4 tumors and a subset of metastases. PD-1+ lymphocytes were found in 50% of DTCs. PD-L1 was expressed by tumor and associated leukocytes in 13 of 22 cases, and expression was more diffuse in anaplastic thyroid cancer (P = .0373). BRAFV600E mutation was associated with higher frequencies of tumor-associated lymphocytes (P = .0095) but not PD-L1 expression. Conclusions: PD-1 checkpoint blockades may have therapeutic efficacy in patients with aggressive forms of thyroid cancer. PMID:27045886

  6. Novel specific heat and magnetoresistance behavior of Tb0.5Ho0.5Mn2Si2

    NASA Astrophysics Data System (ADS)

    Pandey, Swati; Siruguri, V.; Rawat, R.

    2018-04-01

    In this report, we study temperature dependent heat capacity and electrical resistance of Tb1-xHoxMn2Si2 (x = 0.5). Two successive low temperature magnetic transitions T1 (˜15 K) and T2 (˜25 K) are observed from both measurements. Anomalous rise in heat capacity at low temperatures is ascribed to the nuclear Schottky effect. Sommerfeld coefficient (γ), Debye temperature (θD) and density of states at Fermi level N(EF) is calculated from the zero field specific heat data. We observe 4f contribution to heat capacity from T1 to 100K, which is attributed to crystal field effect. In the electrical transport study, application of the magnetic field shows a substantial change around the ordering temperature of rare earth moment resulting in large positive magnetoresistance of about 20% with field change of 6T.

  7. CD8 T Cells and Immunoediting of Breast Cancer

    DTIC Science & Technology

    2008-08-01

    Reiman , C.J. Krco, I.T. Lamborn, and K.L. Knutson. CD8 T cells promote relapse of breast cancer by inducing epithelial to mesenchymal transition. J...Immunother 2006;29:682 (Abstract). 8 Santisteban, M., J.M. Reiman , M.K. Asiedu, M.D. Behrens, A. Nassar, K.R. Kalli, P. Haluska, J.N. Ingle, L.C...immune mechanisms, and their association with prognostic indicators. Surgery 2003;134(5):827-34. 3. Behrens, M.D., J. Reiman , C.J. Krco, I.T. Lamborn

  8. Cohort Profile: the National Prostate Cancer Register of Sweden and Prostate Cancer data Base Sweden 2.0.

    PubMed

    Van Hemelrijck, Mieke; Wigertz, Annette; Sandin, Fredrik; Garmo, Hans; Hellström, Karin; Fransson, Per; Widmark, Anders; Lambe, Mats; Adolfsson, Jan; Varenhorst, Eberhard; Johansson, Jan-Erik; Stattin, Pär

    2013-08-01

    In 1987, the first Regional Prostate Cancer Register was set up in the South-East health-care region of Sweden. Other health-care regions joined and since 1998 virtually all prostate cancer (PCa) cases are registered in the National Prostate Cancer Register (NPCR) of Sweden to provide data for quality assurance, bench marking and clinical research. NPCR includes data on tumour stage, Gleason score, serum level of prostate-specific antigen (PSA) and primary treatment. In 2008, the NPCR was linked to a number of other population-based registers by use of the personal identity number. This database named Prostate Cancer data Base Sweden (PCBaSe) has now been extended with more cases, longer follow-up and a selection of two control series of men free of PCa at the time of sampling, as well as information on brothers of men diagnosed with PCa, resulting in PCBaSe 2.0. This extension allows for studies with case-control, cohort or longitudinal case-only design on aetiological factors, pharmaceutical prescriptions and assessment of long-term outcomes. The NPCR covers >96% of all incident PCa cases registered by the Swedish Cancer Register, which has an underreporting of <3.7%. The NPCR is used to assess trends in incidence, treatment and outcome of men with PCa. Since the national registers linked to PCBaSe are complete, studies from PCBaSe 2.0 are truly population based.

  9. Factors predicting biochemical recurrence after radical prostatectomy among patients with clinical T3 prostate cancer.

    PubMed

    Otsuka, Masafumi; Kamasako, Tomohiko; Uemura, Toshihiro; Takeshita, Nobushige; Shinozaki, Tetsuo; Kobayashi, Masayuki; Komaru, Atsushi; Fukasawa, Satoshi

    2018-06-19

    The effectiveness of cancer control is unclear after radical prostatectomy for patients with clinical T3 prostate cancer. We retrospectively reviewed 1409 patients who underwent radical prostatectomy between April 2007 and December 2014, including 210 patients with cT3 prostate cancer. Nine patients who received neoadjuvant hormonal therapy and three patients who were lost to follow-up were excluded from the analysis. Clinical staging was performed by an experienced radiologist using preoperative magnetic resonance imaging findings. We analyzed the predictors of biochemical recurrence using Cox proportional hazard analyses. A total of 113 patients (57%) underwent radical retropubic prostatectomy and 85 patients (43%) underwent robot-assisted radical prostatectomy. The median follow-up period was 36 months. Downstaging occurred for 60 patients (30%), positive surgical margins were identified in 117 patients (59%), and biochemical recurrence was observed for 89 patients (45%). In the multivariate analyses, the independent preoperative predictors of biochemical recurrence were ≥50% proportion of positive biopsy cores [hazard ratio (HR): 2.858, P < 0.0001] and a biopsy Gleason score of ≥8 (HR: 1.800, P = 0.0093). The independent post-operative predictors of biochemical recurrence were positive surgical margins (HR: 2.490, P = 0.0018) and seminal vesicle invasion (HR: 2.750, P < 0.0001). Among patients with cT3 prostate cancer, the percentage of positive biopsy cores and the biopsy Gleason score should be considered to select treatment. Compared with radical retropubic prostatectomy, robot-assisted radical prostatectomy may be a feasible treatment option in this setting.

  10. N = 20 super no-scale models and moduli quantum stability

    NASA Astrophysics Data System (ADS)

    Kounnas, Costas; Partouche, Hervé

    2017-06-01

    We consider a class of heterotic N = 20 super no-scale Z2-orbifold models. An appropriate stringy Scherk-Schwarz supersymmetry breaking induces tree level masses to all massless bosons of the twisted hypermultiplets and therefore stabilizes all twisted moduli. At high supersymmetry breaking scale, the tachyons that occur in the N = 4 → 0 parent theories are projected out, and no Hagedorn-like instability takes place in the N = 20 models (for small enough marginal deformations). At low supersymmetry breaking scale, the stability of the untwisted moduli is studied at the quantum level by taking into account both untwisted and twisted contributions to the 1-loop effective potential. The latter depends on the specific branch of the gauge theory along which the background can be deformed. We derive its expression in terms of all classical marginal deformations in the pure Coulomb phase, and in some mixed Coulomb/Higgs phases. In this class of models, the super no-scale condition requires having at the massless level equal numbers of untwisted bosonic and twisted fermionic degrees of freedom. Finally, we show that N = 1 → 0 super no-scale models are obtained by implementing a second Z2 orbifold twist on N = 20 super no-scale Z2-orbifold models.

  11. Active cigarette smoking and the risk of breast cancer at the level of N-acetyltransferase 2 (NAT2) gene polymorphisms.

    PubMed

    Kasajova, Petra; Holubekova, Veronika; Mendelova, Andrea; Lasabova, Zora; Zubor, Pavol; Kudela, Erik; Biskupska-Bodova, Kristina; Danko, Jan

    2016-06-01

    The aim of our study was to assess the correlation between the tobacco exposure and NAT2 gene (rs1041983 C/T, rs1801280 T/C, rs1799930 G/A) polymorphisms in association with breast cancer development. We wanted to determine the prognostic clinical importance of these polymorphisms in association with smoking and breast cancer. For the detection of possible association between smoking, NAT2 gene polymorphisms, and the risk of breast cancer, we designed a case-controlled study with 198 patients enrolled, 98 breast cancer patients and 100 healthy controls. Ten milliliters of peripheral blood from the cubital vein was withdrawn from every patient. The HRM (high resolution melting) analysis was used for the detection of three abovementioned NAT2 gene polymorphisms. When comparing a group of women smoking more than 5 cigarettes a day with the patients smoking fewer than 5 cigarettes a day, we found out that if women were the carriers of aberrant AA genotype for rs1799930, the first group of women had higher risk of breast carcinoma than the second group. If patients were the carriers of aberrant TT genotype for rs1041983, for rs1801280CC genotype, and rs1799930AA genotype and they smoked more than 5 cigarettes a day, they had higher risk of malignant breast disease than never-smoking women. Our results confirm the hypothesis that NAT2 gene polymorphisms (rs1041983 C/T, rs1801280 T/C, and rs1799930 G/A) in association with long-period active smoking could be the possible individual risk-predicting factors for breast cancer development in the population of Slovak women.

  12. Vaccines 2.0 | Center for Cancer Research

    Cancer.gov

    In 1974, Jay A. Berzofsky, M.D., Ph.D., now Chief of CCR’s Vaccine Branch, came to NIH to study protein folding. His curious mind and collaborative spirit quickly led him into the intertwined fields of immunology and vaccine development. With close to 500 publications to his name, Berzofsky has pioneered the characterization of B- and T-cell epitopes and their modification to make vaccines directed against cancer and chronic infectious diseases. He has also characterized and taken advantage of the cellular and molecular regulators of immune responses in order to enhance tumor immunity and vaccine efficacy. In the last several years, he has translated many of these strategies into promising clinical trials. From the microcosm of his laboratory, he brings the same spirit of cross-fertilizing, bench-to-bedside research to leading the Vaccine Branch as a whole.

  13. Discovery of novel N-(5-(arylcarbonyl)thiazol-2-yl)amides and N-(5-(arylcarbonyl)thiophen-2-yl)amides as potent RORγt inhibitors.

    PubMed

    Wang, Yonghui; Cai, Wei; Zhang, Guifeng; Yang, Ting; Liu, Qian; Cheng, Yaobang; Zhou, Ling; Ma, Yingli; Cheng, Ziqiang; Lu, Sijie; Zhao, Yong-Gang; Zhang, Wei; Xiang, Zhijun; Wang, Shuai; Yang, Liuqing; Wu, Qianqian; Orband-Miller, Lisa A; Xu, Yan; Zhang, Jing; Gao, Ruina; Huxdorf, Melanie; Xiang, Jia-Ning; Zhong, Zhong; Elliott, John D; Leung, Stewart; Lin, Xichen

    2014-01-15

    Novel series of N-(5-(arylcarbonyl)thiazol-2-yl)amides and N-(5-(arylcarbonyl)thiophen-2-yl)amides were discovered as potent retinoic acid receptor-related orphan receptor-gamma-t (RORγt) inhibitors. SAR studies of the RORγt HTS hit 6a led to identification of thiazole ketone amide 8h and thiophene ketone amide 9g with high binding affinity and inhibitory activity of Th17 cell differentiation. Compound 8h showed in vivo efficacy in both mouse experimental autoimmune encephalomyelitis (EAE) and collagen induced arthritis (CIA) models via oral administration. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Investigation of Regional Influence of Magic-Angle Effect on T2 in Human Articular Cartilage with Osteoarthritis at 3 T

    PubMed Central

    Wang, Ligong; Regatte, Ravinder R.

    2014-01-01

    Rationale and Objectives The objectives of this research study were to determine the magic-angle effect on different subregions of in vivo human femoral cartilage through the quantitative assessment of the effect of static magnetic field orientation (B0) on transverse (T2) relaxation time at 3.0 T. Materials and Methods Healthy volunteers (n = 5l; mean age, 36.4 years) and clinical patients (n = 5; mean age, 64 years) with early osteoarthritis (OA) were scanned at 3.0-T magnetic resonance using an 8-channel phased-array knee coil (transmit-receive). Results The T2 maps revealed significantly greater values in ventral than in dorsal regions. When the cartilage regions were oriented at 55° to B0 (magic angle), the longest T2 values were detected in comparison with the neighboring regions oriented 90° and 180° (0°) to B0. The subregions oriented 180° (0°) to B0 showed the lowest T2 values. Conclusions The differences in T2 values of different subregions suggest that magic-angle effect needs to be considered when interpreting cartilage abnormalities in OA patients. PMID:25481517

  15. Evaluation of the 7(th) edition of the UICC-AJCC tumor, node, metastasis classification for esophageal cancer in a Chinese cohort.

    PubMed

    Huang, Yan; Guo, Weigang; Shi, Shiming; He, Jian

    2016-07-01

    To assess and evaluate the prognostic value of the 7(th) edition of the Union for International Cancer Control-American Joint Committee on Cancer (UICC-AJCC) tumor, node, metastasis (TNM) staging system for Chinese patients with esophageal cancer in comparison with the 6(th) edition. A retrospective review was performed on 766 consecutive esophageal cancer patients treated with esophagectomy between 2008 and 2012. Patients were staged according to the 6(th) and 7(th) editions for esophageal cancer respectively. Survival was calculated by the Kaplan-Meier method, and multivariate analysis was performed using Cox regression model. Overall 3-year survival rate was 59.5%. There were significant differences in 3-year survival rates among T stages both according to the 6(th) edition and the 7(th) edition (P<0.001). According to the 7(th) edition, the 3-year survival rates of N0 (75.4%), N1 (65.2%), N2 (39.7%) and N3 (27.3%) patients were significant differences (P<0.001). Kaplan-Meier curve revealed a good discriminatory ability from stage I to IV, except for stage IB, IIA and IIB in the 7(th) edition staging system. Based on the 7(th) edition, the degree of differentiation, tumor length and tumor location were not independent prognostic factors on multivariate analysis. The multivariate analyses suggested that pT-, pN-, pTNM-category were all the independent prognostic factors based on the 6(th) and 7(th) edition staging system. The 7(th) edition of AJCC TNM staging system of esophageal cancer should discriminate pT2-3N0M0 (stage IB, IIA and IIB) better when considering the esophageal squamous cell cancer patients. Therefore, to improve and optimize the AJCC TNM classification for Chinese patients with esophageal cancer, more considerations about the value of tumor grade and tumor location in pT2-3N0M0 esophageal squamous cell cancer should be taken in the next new TNM staging system.

  16. Glycans and cancer: role of N-glycans in cancer biomarker, progression and metastasis, and therapeutics.

    PubMed

    Taniguchi, Naoyuki; Kizuka, Yasuhiko

    2015-01-01

    Glycosylation is catalyzed by various glycosyltransferase enzymes which are mostly located in the Golgi apparatus in cells. These enzymes glycosylate various complex carbohydrates such as glycoproteins, glycolipids, and proteoglycans. The enzyme activity of glycosyltransferases and their gene expression are altered in various pathophysiological situations including cancer. Furthermore, the activity of glycosyltransferases is controlled by various factors such as the levels of nucleotide sugars, acceptor substrates, nucleotide sugar transporters, chaperons, and endogenous lectin in cancer cells. The glycosylation results in various functional changes of glycoproteins including cell surface receptors and adhesion molecules such as E-cadherin and integrins. These changes confer the unique characteristic phenotypes associated with cancer cells. Therefore, glycans play key roles in cancer progression and treatment. This review focuses on glycan structures, their biosynthetic glycosyltransferases, and their genes in relation to their biological significance and involvement in cancer, especially cancer biomarkers, epithelial-mesenchymal transition, cancer progression and metastasis, and therapeutics. Major N-glycan branching structures which are directly related to cancer are β1,6-GlcNAc branching, bisecting GlcNAc, and core fucose. These structures are enzymatic products of glycosyltransferases, GnT-V, GnT-III, and Fut8, respectively. The genes encoding these enzymes are designated as MGAT5 (Mgat5), MGAT3 (Mgat3), and FUT8 (Fut8) in humans (mice in parenthesis), respectively. GnT-V is highly associated with cancer metastasis, whereas GnT-III is associated with cancer suppression. Fut8 is involved in expression of cancer biomarker as well as in the treatment of cancer. In addition to these enzymes, GnT-IV and GnT-IX (GnT-Vb) will be also discussed in relation to cancer. © 2015 Elsevier Inc. All rights reserved.

  17. Polymorphisms in BRCA1 and BRCA2 and risk of epithelial ovarian cancer.

    PubMed

    Wenham, Robert M; Schildkraut, Joellen M; McLean, Kia; Calingaert, Brian; Bentley, Rex C; Marks, Jeffrey; Berchuck, Andrew

    2003-10-01

    Because inherited BRCA1 or BRCA2 mutations strikingly increase ovarian cancer risk, polymorphisms in these genes could represent low penetrance susceptibility alleles. Previous studies of the BRCA2 N372H polymorphism suggested that HH homozygotes have a modestly increased risk of both breast and ovarian cancer. We have examined whether BRCA2 N372H or common amino acid-changing polymorphisms in BRCA1 predispose to ovarian cancer. A population-based, case control study of ovarian cancer was performed in North Carolina. Cases included 312 women with ovarian cancer (76% invasive and 24% borderline) and 401 age- and race-matched controls. Blood DNA from subjects was genotyped for BRCA2 N372H and BRCA1 Q356R and P871L. There was no association between BRCA2 N372H and risk of borderline or invasive epithelial ovarian cancer. The overall odds ratio (OR) for HH homozygotes was 0.8 [95% confidence interval (CI) = 0.4-1.5] and was similar in all subsets, including invasive serous cases. In addition, neither the BRCA1 Q356R (OR = 0.9, 95% CI 0.5-1.4) nor P871L (OR = 0.9, 95% CI 0.6-1.9) polymorphisms were associated with ovarian cancer risk. There was a significant racial difference in allele frequencies of the P871L polymorphism (P = 0.64 in Caucasians, L = 0.76 in African-Americans, P < 0.0001). In this population-based, case control study, common amino acid changing BRCA1 and 2 polymorphisms were not found to affect the risk of developing ovarian cancer.

  18. Clinicopathological outcomes of preoperative chemoradiotherapy using S-1 plus Irinotecan for T4 lower rectal cancer.

    PubMed

    Beppu, Naohito; Yoshie, Hidenori; Kimura, Fumihiko; Aihara, Tsukasa; Doi, Hiroshi; Kamikonya, Norihiko; Matsubara, Nagahide; Tomita, Naohiro; Yanagi, Hidenori; Yamanaka, Naoki

    2016-07-01

    To investigate the clinicopathological outcomes of patients with T4 lower rectal cancer treated using preoperative chemoradiotherapy with S-1 plus Irinotecan. Between 2005 and 2011, 35 patients with T4M0 lower rectal cancer, diagnosed initially as T4a in 12 and as T4b in 23, were treated with 45 Gy of radiotherapy concomitantly with S-1 plus Irinotecan. The median follow-up period was 50.6 months (range 2-123 months). A total of 32 patients (91.4 %) completed the radiotherapy and 26 (74.3 %) completed the full chemotherapy regimen. Radical surgery was then performed in 33 (94.3 %) of the 35 patients after the exclusion of two patients, who had macroscopic residual disease. The pathological diagnosis was downstaged from T4a to ypT0-3 in all 12 of those patients (100 %) and from T4b to ypT0-4a in 20 of those 23 patients (87.0 %). The tumor regression grade of 1a/1b/2/3 (complete response) was 10/8/15/2, respectively. In terms of long-term survival, the 5-year local relapse-free survival rate was 74.8 % and the recurrence-free survival rate was 52.0 %. This regimen may result in favorable downstaging. Moreover, in this series, pathological evidence of involvement of adjacent organs was rare following preoperative chemoradiotherapy, in the patients with disease diagnosed as T4b at the initial staging.

  19. Colorectal cancer and 18FDG-PET/CT: What about adding the T to the N parameter in loco-regional staging?

    PubMed Central

    Mainenti, Pier Paolo; Iodice, Delfina; Segreto, Sabrina; Storto, Giovanni; Magliulo, Mario; Palma, Giovanni Domenico De; Salvatore, Marco; Pace, Leonardo

    2011-01-01

    AIM: To evaluate whether FDG-positron emission tomography (PET)/computed tomography (CT) may be an accurate technique in the assessment of the T stage in patients with colorectal cancer. METHODS: Thirty four consecutive patients (20 men and 14 women; mean age: 63 years) with a histologically proven diagnosis of colorectal adenocarcinoma and scheduled for surgery in our hospital were enrolled in this study. All patients underwent FDG-PET/CT preoperatively. The primary tumor site and extent were evaluated on PET/CT images. Colorectal wall invasion was analysed according to a modified T classification that considers only three stages (≤ T2, T3, T4). Assessment of accuracy was carried out using 95% confidence intervals for T. RESULTS: Thirty five/37 (94.6%) adenocarcinomas were identified and correctly located on PET/CT images. PET/CT correctly staged the T of 33/35 lesions identified showing an accuracy of 94.3% (95% CI: 87%-100%). All T1, T3 and T4 lesions were correctly staged, while two T2 neoplasms were overstated as T3. CONCLUSION: Our data suggest that FDG-PET/CT may be an accurate modality for identifying primary tumor and defining its local extent in patients with colorectal cancer. PMID:21472100

  20. Systematic review and meta-analysis of the effect of metformin treatment on overall mortality rates in women with endometrial cancer and type 2 diabetes mellitus.

    PubMed

    Perez-Lopez, Faustino R; Pasupuleti, Vinay; Gianuzzi, Ximena; Palma-Ardiles, Gabriela; Hernandez-Fernandez, Wendy; Hernandez, Adrian V

    2017-07-01

    Obesity, insulin resistance and type 2 diabetes mellitus (T2DM) have been associated with endometrial cancer (EC). In this systematic review and meta-analysis we evaluated the effect of metformin on clinical outcomes in patients with EC and insulin resistance or T2DM. Four research databases were searched for original articles published in all languages up to 30 October 2016. Outcomes of interest were overall mortality (OM), cancer-specific mortality, disease progression, and metastases. We performed a random effect meta-analysis of adjusted effects expressed as hazard ratios (HR); heterogeneity among studies was described with the I 2 statistic. Of the 290 retrieved citations, 6 retrospective cohort studies in women with EC (n=4723) met the inclusion criteria, and 8.9% to 23.8% were treated with metformin; OM data was available from 5 studies. In 4 studies of EC patients (n=4132), metformin use was associated with a significant reduction in OM in comparison with not using metformin (adjusted HR [aHR] 0.64, 95% CI 0.45-0.89, p=0.009). In three studies evaluating patients with EC and T2DM (n=2637), metformin use was associated with a significant reduction in OM (aHR 0.50, 95%CI 0.34-0.74, p=0.0006). There was low to moderate heterogeneity of adjusted effects across studies. There was no information about the effect of metformin on cancer-specific mortality, disease progression, or metastases. Metformin treatment is associated with a significant reduction in OM irrespective of diabetes status in patients with EC. The survival benefit suggests that diabetes screening and maintenance of good glycemic control may improve outcomes in EC. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. [miR-503-5p inhibits the proliferation of T24 and EJ bladder cancer cells by interfering with the Rb/E2F signaling pathway].

    PubMed

    Li, Xiaohui; Han, Xingtao; Yang, Jinhui; Sun, Jiantao; Wei, Pengtao

    2017-10-01

    Objective To observe the effect of microRNA-503-5p (miR-503-5p) on the growth of T24 and EJ bladder cancer cells, and explore the possible molecular mechanism. Methods The miR-504-5p mimics or miR-NC was transfected into T24 and EJ cells. The target gene of miR-503-5p was predicted by bioinformatics. The expressions of E2F transcription factor 3 (E2F3) mRNA and Rb/E2F signaling pathway mRNA were detected by the real-time quantitative PCR (qPCR). The expressions of Rb/E2F signal pathway proteins E2F3, cyclin E, CDK2, Rb and p-Rb were detected by Western blotting. The cell cycle of bladder cancer cell lines was determined by flow cytometry. MTT assay and plate cloning assay were performed to observe the proliferation ability of bladder cancer cells. Results After miR-503-5p mimics transfection, the expression of miR-503-5p in bladder cancer cells significantly increased. The increased expression of miR-503-5p significantly reduced the expressions of E2F3 mRNA and Rb/E2F signaling pathway mRNA in bladder cancer cells. What's more, the expressions of Rb/E2F signal pathway proteins were down-regulated. The bladder cancer cells were arrested in G0/G1 phase, and their growth was significantly inhibited by miR-503-5p. Conclusion The miR-503-5p over-expression can inhibit the growth of bladder cancer cell lines T24 and EJ by down-regulating the expression of the Rb/E2F signaling pathway.

  2. The 116G > A MSH6 and IVS1-1121C > T PMS2 Genes Polymorphisms Modulate the Risk of the Sporadic Colorectal Cancer Development in Polish Population.

    PubMed

    Zelga, Piotr; Przybyłowska-Sygut, Karolina; Zelga, Marta; Dziki, Adam; Majsterek, Ireneusz

    2018-04-01

    Colorectal cancer (CRC) is one of the most common cancers worldwide. DNA mismatch repair (MMR) is an evolutionarily conserved process that corrects mismatches generated during DNA replication. MMR defects were found to be associated with hereditary non-polyposis colorectal cancer (HNPCC) and a subset of sporadic colon cancers. The inheritance of common variations in MMR genes may influences individual susceptibility to the development of colorectal cancer. The purpose of the study was to evaluate the association between gene polymorphisms Glu39Gly (c.116G > A) of MSH6 gene and IVS1-1121C > T of PMS2 gene and sporadic colorectal cancer risk, in a case-control study comprising 200 patients and 200 controls origination from polish population. DNA was isolated from peripheral blood lymphocytes of enrolled patients, and gene polymorphisms were analysed by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) for MSH6 and TaqMan for PMS2. G/A variant of Glu39Gly (c.116G > A) genotype was associated with an increased risk of colorectal cancer (OR 1,65 95%CI:1,01-2,69 p = 0.44). Presence of A allele was also significantly higher in patient with CRC (OR 1,57 95% CI: 1,04-2,38 p = 0.032). Prevalence of this genotype was also markedly higher in females and patients above 60 years in CRC group (OR 2.25 95%CI: 1.22-4.14 p = 0.0098 and OR 2.74 95% CI: 1.27-5.93 p = 0.0097 respectively). None of such correlations was observed for genotype variants of IVS1-1121C > T PMS2. In conclusion, our data suggests thatMSH6 Glu39Gly polymorphism is associated with the risk of developing sporadic colorectal cancer in polish population. Linkage to the female gender, onset above 60 years old and further increase of risk when combined with wild-type allele of PMS2 IVS1-1121C > T polymorphism indicates defective mismatch repair system.

  3. High transport current superconductivity in powder-in-tube Ba0.6K0.4Fe2As2 tapes at 27 T

    NASA Astrophysics Data System (ADS)

    Huang, He; Yao, Chao; Dong, Chiheng; Zhang, Xianping; Wang, Dongliang; Cheng, Zhe; Li, Jianqi; Awaji, Satoshi; Wen, Haihu; Ma, Yanwei

    2018-01-01

    The high upper critical field and low anisotropy of iron-based superconductors (IBS) make them particularly attractive for high-field applications, especially for the construction of next-generation nuclear magnetic resonance spectrometers, particle accelerators and high-field magnets. However, for practical use it is essential to make IBS materials into wire and tape conductors with sufficient current carrying capability, which is limited by misaligned grains inside the conductors. Here, based on a simple and low-cost powder-in-tube (PIT) method, we demonstrate a high transport critical current density (J c) reaching 1.5 × 105 A cm-2 (I c = 437 A) at 4.2 K and 10 T in Ba0.6K0.4Fe2As2 (Ba-122) tapes by texturing the grain orientation with optimized hot-press technique. The transport J c measured at 4.2 K under high magnetic fields of 27 T is still on the level of 5.5 × 104 A cm-2. Moreover, at 20 K and 5 T the transport J c is also as high as 5.4 × 104 A cm-2, showing a promising application potential in moderate temperature range which can be reached by liquid hydrogen or cryogenic cooling. All these J c values are the highest ever reported for IBS wires and tapes. The high-performance PIT Ba-122 tapes in this work suggest IBS to be a strong potential competitor of cuprate superconductors for the race of high-field applications in the future.

  4. Exciton localization in polar and semipolar (112̅2) In0.2Ga0.8N/GaN multiple quantum wells

    NASA Astrophysics Data System (ADS)

    Dinh, Duc V.; Presa, Silvino; Maaskant, Pleun P.; Corbett, Brian; Parbrook, Peter J.

    2016-08-01

    The exciton localization (ELZ) in polar (0001) and semipolar (112̅2) In{}0.2Ga{}0.8{{N}} multiple-quantum-well (MQW) structures has been studied by excitation power density and temperature dependent photoluminescence. The ELZ in the (112̅2) MQW was found to be much stronger (ELZ degree σ E ˜ 40 -70 meV) compared to the (0001) MQW (σ E ˜ 5-11 meV) that was attributed to the anisotropic growth on the (112̅2) surface. This strong ELZ was found to cause a blue-shift of the (112̅2) MQW exciton emission with rising temperature from 200 to 340 K, irrespective of excitation source used. A lower luminescence efficiency of the (112̅2) MQW was attributed to their anisotropic growth, and higher concentrations of unintentional impurities and point defects than the (0001) MQW.

  5. Early Postoperative FDG-PET-CT Imaging Results in a Relevant Upstaging in the pN2 Subgroup of Stage III Colorectal Cancer Patients.

    PubMed

    Fehr, Martin; Müller, Joachim; Knitel, Meinhard; Fornaro, Jürgen; Horber, Daniel; Koeberle, Dieter; Cerny, Thomas; Güller, Ulrich

    2017-12-01

    Clinical practice guidelines regarding follow-up in patients after curative resection of colorectal cancer (CRC) vary widely. Current follow-up recommendations do not include additional postoperative imaging before starting adjuvant treatment in any patients. We evaluated the potential benefit of our institutional approach, recommending 18 fluor-deoxy-glucose (FDG)-positron emission tomography (PET)-computed tomography (CT) imaging in CRC stage III patients with ≥4 locoregional lymph node metastases (pN2). Our study included all patients from a single center with complete resection of a pT1-4, pN2, cM0 CRC. All patients were considered free of distant metastases on the basis of preoperative CT imaging of the chest, abdomen, and pelvis. The main objective of the present study was to assess the proportion of patients with changes of therapeutic management (defined as any other treatment than the preplanned adjuvant chemotherapy) because of the results of additional postoperative FDG-PET-CT imaging. Fifty patients (22 female/28 male) were included; the median age was 64 years (range, 37-78 years). Previously undiagnosed metastatic disease resulting in a change of the therapeutic management was detected using postoperative FDG-PET-CT imaging in 7 patients (14.0%; 95% confidence interval, 5.8%-26.7%). The number needed to screen to detect new or previously occult metastases was 7 (7 of 50). To our knowledge, this is the first study to evaluate the role of an additional postoperative FDG-PET-CT scan before adjuvant treatment in patients with completely resected CRC with ≥4 lymph node metastases (pT1-4, pN2) and without distant metastases on preoperative CT imaging (cM0). Postoperative FDG-PET-CT imaging represents a valuable tool for the detection of new macrometastases in the subgroup of pN2 cM0 CRC patients. The low number needed to screen for consequent therapeutic changes is clinically relevant and should be further evaluated. Copyright © 2017 Elsevier Inc

  6. Correlation of apparent diffusion coefficient ratio on 3.0T MRI with prostate cancer Gleason score.

    PubMed

    Jyoti, Rajeev; Jain, Tarun Pankaj; Haxhimolla, Hodo; Liddell, Heath; Barrett, Sean Edward

    2018-01-01

    The purpose was to investigate the usefulness of ADC ratio on Diffusion MRI to discriminate between benign and malignant lesions of Prostate. Images of patients who underwent in-gantry MRI guided prostate lesion biopsy were retrospectively analyzed. Prostate Cancers with 20% or more Gleason score (GS) pattern 3 + 3 = 6 in each core or any volume of higher Gleason score pattern were included. ADC ratio was calculated by two reviewers for each lesion. The ADC ratio was calculated for each lesion by dividing the lowest ADC value in a lesion and highest ADC value in normal prostate in peripheral zone (PZ). ADC ratio values were compared with the biopsy result. Data was analysed using independent samples T-test, Spearman correlation, intra-class correlation coefficient (ICC) and Receiver operating characteristic (ROC) curve. 45 lesions in 33 patients were analyzed. 12 lesions were in transitional zone (TZ) and 33 in perpheral zone PZ. All lesions demonstrated an ADC ratio of 0.45 or lower. GS demonstrated a negative correlation with both the ADC value and ADC ratio . However, ADC ratio (p < 0.001) demonstrated a stronger correlation compared to ADC value alone (p = 0.014). There was no significant statistical difference between GS 3 + 4 and GS 4 + 3 mean ADC tumour value (p = 0.167). However when using ADC ratio , there was a significant difference (p = 0.032). ROC curve analysis demonstrated an area under the curve of 0.83 using ADC ratio and 0.76 when using ADC tumour value when discriminating Gleason 6 from Gleason ≥7 tumours. Inter-observer reliability in the calculation of ADC ratios was excellent, with ICC of 0.964. ADC ratio is a reliable and reproducible tool in quantification of diffusion restriction for clinically significant prostate cancer foci.

  7. N-acetyltransferase 1*10 genotype in bladder cancer patients.

    PubMed

    Höhne, Svetlana; Gerullis, Holger; Blaszkewicz, Meinolf; Selinski, Silvia; Hengstler, Jan G; Otto, Thomas; Golka, Klaus

    2017-01-01

    In a large bladder cancer study in the greater Berlin area with 425 cases and 343 controls, the haplotype N-acetyltransferase 1*10 (NAT1*10) was associated with a decreased bladder cancer risk. In a recently published meta-analysis, results of the studies were found to be inconclusive. Therefore, the aim of this study was to investigate the frequency of NAT1*10 in bladder cancer patients and controls recruited in an area without industries reported to be associated with increased bladder cancer risk. Rs1057126 (1088 T > A) and rs15561 (1095 C > A) were determined in 412 bladder cancer patients and 415 controls without a known history of malignancies. With these two single-nucleotide polymorphisms (SNP), it was possible to distinguish between NAT1*4 (wild type), NAT1*3 (1095 C > A), and NAT1*10 (1088 T > A, 1095C > A). The frequencies of the determined NAT1 haplotypes did not differ markedly between cases and controls: NAT1*4: 74%, NAT1*3: 6%, NAT1*10: 20%. Bladder cancer risk was not significantly modulated by NAT1*10/*10 (OR 1.03, 95% CI 0.71-1.48) but was higher for NAT1*3/*3 genotypes (OR 2.05, 95% CI 1.32-3.21). In contrast to the Berlin study from 2001, data in present study demonstrated that NAT1*10 haplotype was not associated with a significantly decreased bladder cancer risk. This may be due to local effects in the greater Berlin area, particularly at the time of investigation. The findings of the present study are in agreement with observations of a recently published meta-analysis which also showed no relevant impact of NAT1*10 haplotype on bladder cancer risk. The impact of the rare NAT1*3/*3 genotype was significant but this may be attributed to rarity without major practical relevance.

  8. Diagnosis of incidental gallbladder cancer after laparoscopic cholecystectomy: our experience

    PubMed Central

    2013-01-01

    Background Gallbladder carcinoma is a rare high malignancy neoplasm. The incidence of intra or post-operative incidental gallbladder carcinoma diagnosis is estimated between 0,2 and 2,8%. Primary aim of our study is to evaluate incidental gallbladder carcinoma's incidence in our experience. Methods We retrospectively reviewed our Surgery Division's experience about the totality of laparoscopic cholecystectomies with post-operative histological evidence of incidental gallbladder cancer. We evaluated patients' characteristics, surgical related variables, histological response, surgivcal radicalization characteristics and surgical outcome. Results In the considered sample we observed 7 accidental gallbladder adenocarcinomas in post-operative histological examination. Pathological results were:1 pT1b N0 (G1), 2 pT2 N0 (G2), 2 pT2 N1 (G3b), 2 pT3 N1 (G3b) (Table 1). In 5 cases we performed neoplasm radicalization surgery with standard procedure revision. Two patients died before radicalization. Median global survival was 34 months. Conclusion With the increase of laparoscopic cholecystectomies both elective and urgent performed in our centre we observed also an increase of incidentally diagnosed gallbladder neoplasms. Early diagnosis, meticulous peri-operative study and accurate surgical strategy are essential factors to obtain good results in incidental gallbladder cancer. PMID:24268097

  9. Immunohistochemical analysis of PTEN, HER2/neu, and ki67 expression in patients with gastric cancer and their association with survival.

    PubMed

    Badary, Dalia M; Abdel-Wanis, Mostafa E; Hafez, Mohamed Z; Aboulhagag, Noha A

    2017-06-01

    Considering the poor prognosis of patients with gastric cancer, molecular diagnostic and prognostic markers for this cancer should be established. The aims of our study were to assess the correlations between PTEN, HER2/neu, and Ki67 expressions and clinicopathological factors of gastric cancer patients in upper Egypt, as well as their influence on OS and DFS. In this descriptive-analytic study, 42 patients with gastric carcinoma treated by postioerative chemoradiation between 2004 and 2014. Pathological review was done. Immunohistochemical staining and evaluation were performed. All the studied markers were significantly correlated with increased TNM stage. Her2/neu overexpression and positive Ki67 expression were significantly associated with histological grade. High percentage of positive Her2/neu and Ki67expression was found in gastric carcinoma tissue samples which lack PTEN expression. The one-year OS rate for the entire group (n=42) was 77.4%, whereas the DFS rate was 45%. Pathological T stage PTEN status significantly affected both OS (p=0.029 and 0.027 respectively) and DFS (p=0.006 and 0.012 respectively) rates. Multivariate Cox analyses showed that only pathological T stage was an independent prognostic factor affecting OS (P=0. 007, HR: 2.02; 95% CI: 1.2-3.38)and DFS(P<0.0001, HR: 2.69; 95% CI: 1.54-4.69). All the studied molecular markers, was significantly correlated with pathological T stage that significantly affected both OS and DFS rates. These findings indicate that these markers have an important role in gastric cancer growth and dissemination so these markers can be used as a prognostic biomarker. In addition, therapies targeting Her2 and PTEN may help develop novel therapeutics for gastric cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Renal cell carcinoma and a constitutional t(11;22)(q23;q11.2): case report and review of the potential link between the constitutional t(11;22) and cancer.

    PubMed

    Doyen, Jérôme; Carpentier, Xavier; Haudebourg, Juliette; Hoch, Benjamin; Karmous-Benailly, Houda; Ambrosetti, Damien; Fabas, Thibault; Amiel, Jean; Lambert, Jean-Claude; Pedeutour, Florence

    2012-11-01

    We observed a t(11;22)(q23-24;q11.2-12) and monosomy 3 in renal tumor cells from a 72-year-old man. The hypothesis of a primitive peripheral neuroectodermal tumor (PPNET) located in the kidney was promptly excluded: Histologically, the tumor was a clear cell renal cell carcinoma (RCC) and we did not observe an EWSR1 gene rearrangement. The constitutional origin of this alteration was established. We report on the second case of RCC in a patient with a constitutional t(11;22). The t(11;22)(q23;q11.2) is the main recurrent germline translocation in humans. Unbalanced translocation can be transmitted to the progeny and can cause Emanuel syndrome. Our observation alerts cancer cytogeneticists to the fortuitous discovery of the constitutional t(11;22) in tumor cells. This translocation appears grossly similar to the t(11;22)(q24;q12) of PPNET and should be evoked if present in all cells of a tumor other than PPNET. This is important when providing appropriate genetic counseling. Moreover, the potential oncogenic role of the t(11;22) and its predisposing risk of cancer are under debate. The family history of the patient revealed a disabled brother who died at an early age from colon cancer and a sister with breast cancer. This observation reopens the issue of a link between the constitutional t(11;22) and cancer, and the utility of cancer prevention workups for t(11;22) carriers. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Worldwide Esophageal Cancer Collaboration: pathologic staging data.

    PubMed

    Rice, T W; Chen, L-Q; Hofstetter, W L; Smithers, B M; Rusch, V W; Wijnhoven, B P L; Chen, K L; Davies, A R; D'Journo, X B; Kesler, K A; Luketich, J D; Ferguson, M K; Räsänen, J V; van Hillegersberg, R; Fang, W; Durand, L; Cecconello, I; Allum, W H; Cerfolio, R J; Pera, M; Griffin, S M; Burger, R; Liu, J-F; Allen, M S; Law, S; Watson, T J; Darling, G E; Scott, W J; Duranceau, A; Denlinger, C E; Schipper, P H; Lerut, T E M R; Orringer, M B; Ishwaran, H; Apperson-Hansen, C; DiPaola, L M; Semple, M E; Blackstone, E H

    2016-10-01

    We report data-simple descriptions of patient characteristics, cancer categories, and non-risk-adjusted survival-for patients with pathologically staged cancer of the esophagus and esophagogastric junction after resection or ablation with no preoperative therapy from the Worldwide Esophageal Cancer Collaboration (WECC). Thirty-three institutions from six continents submitted de-identified data using standard definitions: demographics, comorbidities, clinical cancer categories, and all-cause mortality from first management decision. Of 13,300 patients, 5,631 had squamous cell carcinoma, 7,558 adenocarcinoma, 85 adenosquamous carcinoma, and 26 undifferentiated carcinoma. Patients were older (62 years) men (80%) with normal body mass index (51%), little weight loss (1.8 kg), 0-2 ECOG performance status (83%), and a history of smoking (70%). Cancers were pT1 (24%), pT2 (15%), pT3 (50%), pN0 (52%), pM0 (93%), and pG2-G3 (78%); most involved distal esophagus (71%). Non-risk-adjusted survival for both squamous cell carcinoma and adenocarcinoma was monotonic and distinctive across pTNM. Survival was more distinctive for adenocarcinoma than squamous cell carcinoma when pT was ordered by pN. Survival for pTis-1 adenocarcinoma was better than for squamous cell carcinoma, although monotonic and distinctive for both. WECC pathologic staging data is improved over that of the 7th edition, with more patients studied and patient and cancer variables collected. These data will be the basis for the 8th edition cancer staging manuals following risk adjustment for patient, cancer, and treatment characteristics, and should direct 9th edition data collection. However, the role of pure pathologic staging as the principal point of reference for esophageal cancer staging is waning. © 2016 International Society for Diseases of the Esophagus.

  12. Worldwide Esophageal Cancer Collaboration: pathologic staging data

    PubMed Central

    Rice, T. W.; Chen, L.-Q.; Hofstetter, W. L.; Smithers, B.M.; Rusch, V. W.; Wijnhoven, B. P. L.; Chen, K. L.; Davies, A. R.; D’Journo, X. B.; Kesler, K. A.; Luketich, J. D.; Ferguson, M. K.; Räsänen, J. V.; van Hillegersberg, R.; Fang, W.; Durand, L.; Cecconello, I.; Allum, W. H.; Cerfolio, R. J.; Pera, M.; Griffin, S. M.; Burger, R.; Liu, J.-F; Allen, M. S.; Law, S.; Watson, T. J.; Darling, G. E.; Scott, W. J.; Duranceau, A.; Denlinger, C. E.; Schipper, P. H.; Lerut, T. E. M. R.; Orringer, M. B.; Ishwaran, H.; Apperson-Hansen, C.; DiPaola, L. M.; Semple, M. E.; Blackstone, E. H.

    2017-01-01

    SUMMARY We report data—simple descriptions of patient characteristics, cancer categories, and non–risk-adjusted survival—for patients with pathologically staged cancer of the esophagus and esophagogastric junction after resection or ablation with no preoperative therapy from the Worldwide Esophageal Cancer Collaboration (WECC). Thirty-three institutions from six continents submitted de-identified data using standard definitions: demographics, comorbidities, clinical cancer categories, and all-cause mortality from first management decision. Of 13,300 patients, 5,631 had squamous cell carcinoma, 7,558 adenocarcinoma, 85 adenosquamous carcinoma, and 26 undifferentiated carcinoma. Patients were older (62 years) men (80%) with normal body mass index (51%), little weight loss (1.8 kg), 02 ECOG performance status (83%), and a history of smoking (70%). Cancers were pT1 (24%), pT2 (15%), pT3 (50%), pN0 (52%), pM0 (93%), and pG2–G3 (78%); most involved distal esophagus (71%). Non–risk-adjusted survival for both squamous cell carcinoma and adenocarcinoma was monotonic and distinctive across pTNM. Survival was more distinctive for adenocarcinoma than squamous cell carcinoma when pT was ordered by pN. Survival for pTis-1 adenocarcinoma was better than for squamous cell carcinoma, although monotonic and distinctive for both. WECC pathologic staging data is improved over that of the 7th edition, with more patients studied and patient and cancer variables collected. These data will be the basis for the 8th edition cancer staging manuals following risk adjustment for patient, cancer, and treatment characteristics, and should direct 9th edition data collection. However, the role of pure pathologic staging as the principal point of reference for esophageal cancer staging is waning. PMID:27731547

  13. Human CD3+ T-Cells with the Anti-ERBB2 Chimeric Antigen Receptor Exhibit Efficient Targeting and Induce Apoptosis in ERBB2 Overexpressing Breast Cancer Cells

    PubMed Central

    Munisvaradass, Rusheni; Kumar, Suresh; Govindasamy, Chandramohan; Alnumair, Khalid S.; Mok, Pooi Ling

    2017-01-01

    Breast cancer is a common malignancy among women. The innate and adaptive immune responses failed to be activated owing to immune modulation in the tumour microenvironment. Decades of scientific study links the overexpression of human epidermal growth factor receptor 2 (ERBB2) antigen with aggressive tumours. The Chimeric Antigen Receptor (CAR) coding for specific tumour-associated antigens could initiate intrinsic T-cell signalling, inducing T-cell activation, and cytotoxic activity without the need for major histocompatibility complex recognition. This renders CAR as a potentially universal immunotherapeutic option. Herein, we aimed to establish CAR in CD3+ T-cells, isolated from human peripheral blood mononucleated cells that could subsequently target and induce apoptosis in the ERBB2 overexpressing human breast cancer cell line, SKBR3. Constructed CAR was inserted into a lentiviral plasmid containing a green fluorescent protein tag and produced as lentiviral particles that were used to transduce activated T-cells. Transduced CAR-T cells were then primed with SKBR3 cells to evaluate their functionality. Results showed increased apoptosis in SKBR3 cells co-cultured with CAR-T cells compared to the control (non–transduced T-cells). This study demonstrates that CAR introduction helps overcome the innate limitations of native T-cells leading to cancer cell apoptosis. We recommend future studies should focus on in vivo cytotoxicity of CAR-T cells against ERBB2 expressing tumours. PMID:28885562

  14. Human CD3+ T-Cells with the Anti-ERBB2 Chimeric Antigen Receptor Exhibit Efficient Targeting and Induce Apoptosis in ERBB2 Overexpressing Breast Cancer Cells.

    PubMed

    Munisvaradass, Rusheni; Kumar, Suresh; Govindasamy, Chandramohan; Alnumair, Khalid S; Mok, Pooi Ling

    2017-09-08

    Breast cancer is a common malignancy among women. The innate and adaptive immune responses failed to be activated owing to immune modulation in the tumour microenvironment. Decades of scientific study links the overexpression of human epidermal growth factor receptor 2 (ERBB2) antigen with aggressive tumours. The Chimeric Antigen Receptor (CAR) coding for specific tumour-associated antigens could initiate intrinsic T-cell signalling, inducing T-cell activation, and cytotoxic activity without the need for major histocompatibility complex recognition. This renders CAR as a potentially universal immunotherapeutic option. Herein, we aimed to establish CAR in CD3+ T-cells, isolated from human peripheral blood mononucleated cells that could subsequently target and induce apoptosis in the ERBB2 overexpressing human breast cancer cell line, SKBR3. Constructed CAR was inserted into a lentiviral plasmid containing a green fluorescent protein tag and produced as lentiviral particles that were used to transduce activated T-cells. Transduced CAR-T cells were then primed with SKBR3 cells to evaluate their functionality. Results showed increased apoptosis in SKBR3 cells co-cultured with CAR-T cells compared to the control (non-transduced T-cells). This study demonstrates that CAR introduction helps overcome the innate limitations of native T-cells leading to cancer cell apoptosis. We recommend future studies should focus on in vivo cytotoxicity of CAR-T cells against ERBB2 expressing tumours.

  15. Biparametric 3T Magnetic Resonance Imaging for prostatic cancer detection in a biopsy-naïve patient population: a further improvement of PI-RADS v2?

    PubMed

    Stanzione, Arnaldo; Imbriaco, Massimo; Cocozza, Sirio; Fusco, Ferdinando; Rusconi, Giovanni; Nappi, Carmela; Mirone, Vincenzo; Mangiapia, Francesco; Brunetti, Arturo; Ragozzino, Alfonso; Longo, Nicola

    2016-12-01

    To prospectively determine the diagnostic accuracy of a biparametric 3T magnetic resonance imaging protocol (BP-MRI) for prostatic cancer detection, compared to a multiparametric MRI protocol (MP-MRI), in a biopsy naïve patient population. Eighty-two untreated patients (mean age 65±7.6years) with clinical suspicion of prostate cancer and/or altered prostate-specific antigen (PSA) levels underwent a MP-MRI, including T2-weighted imaging, diffusion-weighted imaging (with the correspondent apparent diffusion coefficient maps) and dynamic contrast enhanced sequence, followed by prostate biopsy. Two radiologists reviewed both the BP-MRI and the MP-MRI protocols to establish a radiological diagnosis. Receiver operating characteristics curves were obtained to determine the diagnostic performance of the two protocols. The mean PSA level was 8.8±8.1ng/ml. A total of 34 prostatic tumors were identified, with a Gleason score that ranged from 3+3 to 5+4. Of these 34 tumors, 29 were located within the peripheral zone and 5 in the transitional zone. BP-MRI and MP-MRI showed a similar performance in terms of overall diagnostic accuracy, with an area under the curve of 0.91 and 0.93, respectively (p=n.s.). BP-MRI prostate protocol is feasible for prostatic cancer detection compared to a standard MP-MRI protocol, requiring a shorter acquisition and interpretation time, with comparable diagnostic accuracy to the conventional protocol, without the administration of gadolinium-based contrast agent. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. Breast Lesions: Diagnosis Using Diffusion Weighted Imaging at 1.5T and 3.0T-Systematic Review and Meta-analysis.

    PubMed

    Shi, Ruo-Yang; Yao, Qiu-Ying; Wu, Lian-Ming; Xu, Jian-Rong

    2018-06-01

    We compared the diagnostic performance of diffusion weighted imaging (DWI) acquired with 1.5T and 3.0T magnetic resonance (MR) units in differentiating malignant breast lesions from benign ones. A comprehensive search of the PubMed and Embase databases was performed for studies reported from January 1, 2000 to February 19, 2016. The quality of the included studies was assessed. Statistical analysis included pooling of diagnostic sensitivity and specificity and assessing data inhomogeneity and publication bias. A total of 61 studies were included after a full-text review. These included 4778 patients and 5205 breast lesions. The overall sensitivity and specificity were 90% (95% confidence interval [CI], 88%-92%) and 86% (95% CI, 82%-89%), respectively. The pooled diagnostic odds ratio was 53 (95% CI, 37-74). For breast cancer versus benign lesions, the area under the curve was 0.94 (95% CI, 0.92-0.96). For the 44 studies that used a 1.5T MR unit, the pooled sensitivity and specificity were 91% (95% CI, 89%-92%) and 86% (95% CI, 81%-90%), respectively. For the 17 studies that used a 3.0T MR unit, the pooled sensitivity and specificity were 88% (95% CI, 83%-91%) and 84% (95% CI, 0.78-0.89), respectively. Publication bias and significant heterogeneity were observed; however, no threshold was found among the 61 studies. No significant difference was found in the sensitivity or specificity between the subgroups. The results of the comparison between the subgroups that had used either a 1.5T or 3.0T MR unit suggest that the diagnostic accuracy for breast cancer compared with benign lesions is not significantly different. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. A novel germline PALB2 deletion in Polish breast and ovarian cancer patients.

    PubMed

    Dansonka-Mieszkowska, Agnieszka; Kluska, Anna; Moes, Joanna; Dabrowska, Michalina; Nowakowska, Dorota; Niwinska, Anna; Derlatka, Pawel; Cendrowski, Krzysztof; Kupryjanczyk, Jolanta

    2010-02-02

    PALB2 protein was recently identified as a partner of BRCA1 and BRCA2 which determines their proper function in DNA repair. Initially, the entire coding sequence of the PALB2 gene with exon/intron boundaries was evaluated by the PCR-SSCP and direct sequencing methods on 70 ovarian carcinomas. Sequence variants of interest were further studied on enlarged groups of ovarian carcinomas (total 339 non-consecutive ovarian carcinomas), blood samples from 334 consecutive sporadic and 648 consecutive familial breast cancer patients, and 1310 healthy controls from central Poland. Ten types of sequence variants were detected, and among them four novel polymorphisms: c.2996+58T>C in intron 9; c.505C>A (p.L169I), c.618T>G (p.L206L), both in exon 4; and c.2135C>T (A712V) in exon 5 of the PALB2 gene. Another two polymorphisms, c.212-58A>C and c.2014G>C (E672Q) were always detected together, both in cancer (7.5% of patients) and control samples (4.9% of controls, p = 0.2). A novel germline truncating mutation, c.509_510delGA (p.R170fs) was found in exon 4: in 2 of 339 (0.6%) unrelated ovarian cancer patients, in 4 of 648 (0.6%) unrelated familial breast cancer patients, and in 1 of 1310 controls (0.08%, p = 0.1, p = 0.044, respectively). One ovarian cancer patient with the PALB2 mutation had also a germline nonsense mutation of the BRCA2 gene. The c.509_510delGA is a novel PALB2 mutation that increases the risk of familial breast cancer. Occurrence of the same PALB2 alteration in seven unrelated women suggests that c.509_510delGA (p.R170fs) is a recurrent mutation for Polish population.

  18. Measurement of Prompt D0 Meson Azimuthal Anisotropy in Pb-Pb Collisions at √{sN N }=5.02 TeV

    NASA Astrophysics Data System (ADS)

    Sirunyan, A. M.; Tumasyan, A.; Adam, W.; Ambrogi, F.; Asilar, E.; Bergauer, T.; Brandstetter, J.; Brondolin, E.; Dragicevic, M.; Erö, J.; Flechl, M.; Friedl, M.; Frühwirth, R.; Ghete, V. M.; Grossmann, J.; Hrubec, J.; Jeitler, M.; König, A.; Krammer, N.; Krätschmer, I.; Liko, D.; Madlener, T.; Mikulec, I.; Pree, E.; Rabady, D.; Rad, N.; Rohringer, H.; Schieck, J.; Schöfbeck, R.; Spanring, M.; Spitzbart, D.; Waltenberger, W.; Wittmann, J.; Wulz, C.-E.; Zarucki, M.; Chekhovsky, V.; Mossolov, V.; Suarez Gonzalez, J.; De Wolf, E. A.; Di Croce, D.; Janssen, X.; Lauwers, J.; Van Haevermaet, H.; Van Mechelen, P.; Van Remortel, N.; Abu Zeid, S.; Blekman, F.; D'Hondt, J.; De Bruyn, I.; De Clercq, J.; Deroover, K.; Flouris, G.; Lontkovskyi, D.; Lowette, S.; Moortgat, S.; Moreels, L.; Python, Q.; Skovpen, K.; Tavernier, S.; Van Doninck, W.; Van Mulders, P.; Van Parijs, I.; Brun, H.; Clerbaux, B.; De Lentdecker, G.; Delannoy, H.; Fasanella, G.; Favart, L.; Goldouzian, R.; Grebenyuk, A.; Karapostoli, G.; Lenzi, T.; Luetic, J.; Maerschalk, T.; Marinov, A.; Randle-conde, A.; Seva, T.; Vander Velde, C.; Vanlaer, P.; Vannerom, D.; Yonamine, R.; Zenoni, F.; Zhang, F.; Cimmino, A.; Cornelis, T.; Dobur, D.; Fagot, A.; Gul, M.; Khvastunov, I.; Poyraz, D.; Roskas, C.; Salva, S.; Tytgat, M.; Verbeke, W.; Zaganidis, N.; Bakhshiansohi, H.; Bondu, O.; Brochet, S.; Bruno, G.; Caudron, A.; De Visscher, S.; Delaere, C.; Delcourt, M.; Francois, B.; Giammanco, A.; Jafari, A.; Komm, M.; Krintiras, G.; Lemaitre, V.; Magitteri, A.; Mertens, A.; Musich, M.; Piotrzkowski, K.; Quertenmont, L.; Vidal Marono, M.; Wertz, S.; Beliy, N.; Aldá Júnior, W. L.; Alves, F. L.; Alves, G. A.; Brito, L.; Correa Martins Junior, M.; Hensel, C.; Moraes, A.; Pol, M. E.; Rebello Teles, P.; Belchior Batista Das Chagas, E.; Carvalho, W.; Chinellato, J.; Custódio, A.; Da Costa, E. M.; Da Silveira, G. G.; De Jesus Damiao, D.; Fonseca De Souza, S.; Huertas Guativa, L. M.; Malbouisson, H.; Melo De Almeida, M.; Mora Herrera, C.; Mundim, L.; Nogima, H.; Santoro, A.; Sznajder, A.; Tonelli Manganote, E. J.; Torres Da Silva De Araujo, F.; Vilela Pereira, A.; Ahuja, S.; Bernardes, C. A.; Fernandez Perez Tomei, T. R.; Gregores, E. M.; Mercadante, P. G.; Novaes, S. F.; Padula, Sandra S.; Romero Abad, D.; Ruiz Vargas, J. C.; Aleksandrov, A.; Hadjiiska, R.; Iaydjiev, P.; Misheva, M.; Rodozov, M.; Shopova, M.; Stoykova, S.; Sultanov, G.; Dimitrov, A.; Glushkov, I.; Litov, L.; Pavlov, B.; Petkov, P.; Fang, W.; Gao, X.; Ahmad, M.; Bian, J. G.; Chen, G. M.; Chen, H. S.; Chen, M.; Chen, Y.; Jiang, C. H.; Leggat, D.; Liao, H.; Liu, Z.; Romeo, F.; Shaheen, S. M.; Spiezia, A.; Tao, J.; Wang, C.; Wang, Z.; Yazgan, E.; Zhang, H.; Zhao, J.; Ban, Y.; Chen, G.; Li, Q.; Liu, S.; Mao, Y.; Qian, S. J.; Wang, D.; Xu, Z.; Avila, C.; Cabrera, A.; Chaparro Sierra, L. F.; Florez, C.; González Hernández, C. F.; Ruiz Alvarez, J. D.; Courbon, B.; Godinovic, N.; Lelas, D.; Puljak, I.; Ribeiro Cipriano, P. M.; Sculac, T.; Antunovic, Z.; Kovac, M.; Brigljevic, V.; Ferencek, D.; Kadija, K.; Mesic, B.; Starodumov, A.; Susa, T.; Ather, M. W.; Attikis, A.; Mavromanolakis, G.; Mousa, J.; Nicolaou, C.; Ptochos, F.; Razis, P. A.; Rykaczewski, H.; Finger, M.; Finger, M.; Carrera Jarrin, E.; El-khateeb, E.; Elgammal, S.; Ellithi Kamel, A.; Dewanjee, R. K.; Kadastik, M.; Perrini, L.; Raidal, M.; Tiko, A.; Veelken, C.; Eerola, P.; Pekkanen, J.; Voutilainen, M.; Härkönen, J.; Järvinen, T.; Karimäki, V.; Kinnunen, R.; Lampén, T.; Lassila-Perini, K.; Lehti, S.; Lindén, T.; Luukka, P.; Tuominen, E.; Tuominiemi, J.; Tuovinen, E.; Talvitie, J.; Tuuva, T.; Besancon, M.; Couderc, F.; Dejardin, M.; Denegri, D.; Faure, J. L.; Ferri, F.; Ganjour, S.; Ghosh, S.; Givernaud, A.; Gras, P.; Hamel de Monchenault, G.; Jarry, P.; Kucher, I.; Locci, E.; Machet, M.; Malcles, J.; Negro, G.; Rander, J.; Rosowsky, A.; Sahin, M. Ö.; Titov, M.; Abdulsalam, A.; Antropov, I.; Baffioni, S.; Beaudette, F.; Busson, P.; Cadamuro, L.; Charlot, C.; Granier de Cassagnac, R.; Jo, M.; Lisniak, S.; Lobanov, A.; Martin Blanco, J.; Nguyen, M.; Ochando, C.; Ortona, G.; Paganini, P.; Pigard, P.; Regnard, S.; Salerno, R.; Sauvan, J. B.; Sirois, Y.; Stahl Leiton, A. G.; Strebler, T.; Yilmaz, Y.; Zabi, A.; Zghiche, A.; Agram, J.-L.; Andrea, J.; Bloch, D.; Brom, J.-M.; Buttignol, M.; Chabert, E. C.; Chanon, N.; Collard, C.; Conte, E.; Coubez, X.; Fontaine, J.-C.; Gelé, D.; Goerlach, U.; Jansová, M.; Le Bihan, A.-C.; Tonon, N.; Van Hove, P.; Gadrat, S.; Beauceron, S.; Bernet, C.; Boudoul, G.; Chierici, R.; Contardo, D.; Depasse, P.; El Mamouni, H.; Fay, J.; Finco, L.; Gascon, S.; Gouzevitch, M.; Grenier, G.; Ille, B.; Lagarde, F.; Laktineh, I. B.; Lethuillier, M.; Mirabito, L.; Pequegnot, A. L.; Perries, S.; Popov, A.; Sordini, V.; Vander Donckt, M.; Viret, S.; Khvedelidze, A.; Bagaturia, I.; Autermann, C.; Beranek, S.; Feld, L.; Kiesel, M. K.; Klein, K.; Lipinski, M.; Preuten, M.; Schomakers, C.; Schulz, J.; Verlage, T.; Albert, A.; Dietz-Laursonn, E.; Duchardt, D.; Endres, M.; Erdmann, M.; Erdweg, S.; Esch, T.; Fischer, R.; Güth, A.; Hamer, M.; Hebbeker, T.; Heidemann, C.; Hoepfner, K.; Knutzen, S.; Merschmeyer, M.; Meyer, A.; Millet, P.; Mukherjee, S.; Olschewski, M.; Padeken, K.; Pook, T.; Radziej, M.; Reithler, H.; Rieger, M.; Scheuch, F.; Teyssier, D.; Thüer, S.; Flügge, G.; Kargoll, B.; Kress, T.; Künsken, A.; Lingemann, J.; Müller, T.; Nehrkorn, A.; Nowack, A.; Pistone, C.; Pooth, O.; Stahl, A.; Aldaya Martin, M.; Arndt, T.; Asawatangtrakuldee, C.; Beernaert, K.; Behnke, O.; Behrens, U.; Bermúdez Martínez, A.; Bin Anuar, A. A.; Borras, K.; Botta, V.; Campbell, A.; Connor, P.; Contreras-Campana, C.; Costanza, F.; Diez Pardos, C.; Eckerlin, G.; Eckstein, D.; Eichhorn, T.; Eren, E.; Gallo, E.; Garay Garcia, J.; Geiser, A.; Gizhko, A.; Grados Luyando, J. 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M.; Stöver, M.; Tholen, H.; Troendle, D.; Usai, E.; Vanelderen, L.; Vanhoefer, A.; Vormwald, B.; Akbiyik, M.; Barth, C.; Baur, S.; Butz, E.; Caspart, R.; Chwalek, T.; Colombo, F.; De Boer, W.; Dierlamm, A.; Freund, B.; Friese, R.; Giffels, M.; Gilbert, A.; Haitz, D.; Hartmann, F.; Heindl, S. M.; Husemann, U.; Kassel, F.; Kudella, S.; Mildner, H.; Mozer, M. U.; Müller, Th.; Plagge, M.; Quast, G.; Rabbertz, K.; Schröder, M.; Shvetsov, I.; Sieber, G.; Simonis, H. J.; Ulrich, R.; Wayand, S.; Weber, M.; Weiler, T.; Williamson, S.; Wöhrmann, C.; Wolf, R.; Anagnostou, G.; Daskalakis, G.; Geralis, T.; Giakoumopoulou, V. A.; Kyriakis, A.; Loukas, D.; Topsis-Giotis, I.; Karathanasis, G.; Kesisoglou, S.; Panagiotou, A.; Saoulidou, N.; Evangelou, I.; Foudas, C.; Kokkas, P.; Mallios, S.; Manthos, N.; Papadopoulos, I.; Paradas, E.; Strologas, J.; Triantis, F. 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M.; Khakzad, M.; Mohammadi Najafabadi, M.; Naseri, M.; Paktinat Mehdiabadi, S.; Rezaei Hosseinabadi, F.; Safarzadeh, B.; Zeinali, M.; Felcini, M.; Grunewald, M.; Abbrescia, M.; Calabria, C.; Caputo, C.; Colaleo, A.; Creanza, D.; Cristella, L.; De Filippis, N.; De Palma, M.; Errico, F.; Fiore, L.; Iaselli, G.; Lezki, S.; Maggi, G.; Maggi, M.; Miniello, G.; My, S.; Nuzzo, S.; Pompili, A.; Pugliese, G.; Radogna, R.; Ranieri, A.; Selvaggi, G.; Sharma, A.; Silvestris, L.; Venditti, R.; Verwilligen, P.; Abbiendi, G.; Battilana, C.; Bonacorsi, D.; Braibant-Giacomelli, S.; Campanini, R.; Capiluppi, P.; Castro, A.; Cavallo, F. R.; Chhibra, S. S.; Codispoti, G.; Cuffiani, M.; Dallavalle, G. M.; Fabbri, F.; Fanfani, A.; Fasanella, D.; Giacomelli, P.; Grandi, C.; Guiducci, L.; Marcellini, S.; Masetti, G.; Montanari, A.; Navarria, F. L.; Perrotta, A.; Rossi, A. M.; Rovelli, T.; Siroli, G. 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A.; Lista, L.; Meola, S.; Paolucci, P.; Sciacca, C.; Thyssen, F.; Azzi, P.; Bacchetta, N.; Benato, L.; Bisello, D.; Boletti, A.; Carlin, R.; Carvalho Antunes De Oliveira, A.; Checchia, P.; De Castro Manzano, P.; Dorigo, T.; Dosselli, U.; Gasparini, F.; Gasparini, U.; Gozzelino, A.; Lacaprara, S.; Margoni, M.; Meneguzzo, A. T.; Pozzobon, N.; Ronchese, P.; Rossin, R.; Simonetto, F.; Torassa, E.; Zanetti, M.; Zotto, P.; Zumerle, G.; Braghieri, A.; Fallavollita, F.; Magnani, A.; Montagna, P.; Ratti, S. P.; Re, V.; Ressegotti, M.; Riccardi, C.; Salvini, P.; Vai, I.; Vitulo, P.; Alunni Solestizi, L.; Biasini, M.; Bilei, G. M.; Cecchi, C.; Ciangottini, D.; Fanò, L.; Lariccia, P.; Leonardi, R.; Manoni, E.; Mantovani, G.; Mariani, V.; Menichelli, M.; Rossi, A.; Santocchia, A.; Spiga, D.; Androsov, K.; Azzurri, P.; Bagliesi, G.; Bernardini, J.; Boccali, T.; Borrello, L.; Castaldi, R.; Ciocci, M. A.; Dell'Orso, R.; Fedi, G.; Giannini, L.; Giassi, A.; Grippo, M. T.; Ligabue, F.; Lomtadze, T.; Manca, E.; Mandorli, G.; Martini, L.; Messineo, A.; Palla, F.; Rizzi, A.; Savoy-Navarro, A.; Spagnolo, P.; Tenchini, R.; Tonelli, G.; Venturi, A.; Verdini, P. G.; Barone, L.; Cavallari, F.; Cipriani, M.; Daci, N.; Del Re, D.; Diemoz, M.; Gelli, S.; Longo, E.; Margaroli, F.; Marzocchi, B.; Meridiani, P.; Organtini, G.; Paramatti, R.; Preiato, F.; Rahatlou, S.; Rovelli, C.; Santanastasio, F.; Amapane, N.; Arcidiacono, R.; Argiro, S.; Arneodo, M.; Bartosik, N.; Bellan, R.; Biino, C.; Cartiglia, N.; Cenna, F.; Costa, M.; Covarelli, R.; Degano, A.; Demaria, N.; Kiani, B.; Mariotti, C.; Maselli, S.; Migliore, E.; Monaco, V.; Monteil, E.; Monteno, M.; Obertino, M. M.; Pacher, L.; Pastrone, N.; Pelliccioni, M.; Pinna Angioni, G. L.; Ravera, F.; Romero, A.; Ruspa, M.; Sacchi, R.; Shchelina, K.; Sola, V.; Solano, A.; Staiano, A.; Traczyk, P.; Belforte, S.; Casarsa, M.; Cossutti, F.; Della Ricca, G.; Zanetti, A.; Kim, D. H.; Kim, G. N.; Kim, M. S.; Lee, J.; Lee, S.; Lee, S. W.; Moon, C. S.; Oh, Y. D.; Sekmen, S.; Son, D. C.; Yang, Y. C.; Lee, A.; Kim, H.; Moon, D. H.; Oh, G.; Brochero Cifuentes, J. A.; Goh, J.; Kim, T. J.; Cho, S.; Choi, S.; Go, Y.; Gyun, D.; Ha, S.; Hong, B.; Jo, Y.; Kim, Y.; Lee, K.; Lee, K. S.; Lee, S.; Lim, J.; Park, S. K.; Roh, Y.; Almond, J.; Kim, J.; Kim, J. S.; Lee, H.; Lee, K.; Nam, K.; Oh, S. B.; Radburn-Smith, B. C.; Seo, S. h.; Yang, U. K.; Yoo, H. D.; Yu, G. B.; Choi, M.; Kim, H.; Kim, J. H.; Lee, J. S. H.; Park, I. C.; Ryu, G.; Choi, Y.; Hwang, C.; Lee, J.; Yu, I.; Dudenas, V.; Juodagalvis, A.; Vaitkus, J.; Ahmed, I.; Ibrahim, Z. A.; Md Ali, M. A. B.; Mohamad Idris, F.; Wan Abdullah, W. A. T.; Yusli, M. N.; Zolkapli, Z.; Reyes-Almanza, R.; Ramirez-Sanchez, G.; Duran-Osuna, M. C.; Castilla-Valdez, H.; De La Cruz-Burelo, E.; Heredia-De La Cruz, I.; Rabadan-Trejo, R. I.; Lopez-Fernandez, R.; Mejia Guisao, J.; Sanchez-Hernandez, A.; Carrillo Moreno, S.; Oropeza Barrera, C.; Vazquez Valencia, F.; Pedraza, I.; Salazar Ibarguen, H. A.; Uribe Estrada, C.; Morelos Pineda, A.; Krofcheck, D.; Butler, P. H.; Ahmad, A.; Ahmad, M.; Hassan, Q.; Hoorani, H. R.; Saddique, A.; Shah, M. A.; Shoaib, M.; Waqas, M.; Bialkowska, H.; Bluj, M.; Boimska, B.; Frueboes, T.; Górski, M.; Kazana, M.; Nawrocki, K.; Romanowska-Rybinska, K.; Szleper, M.; Zalewski, P.; Bunkowski, K.; Byszuk, A.; Doroba, K.; Kalinowski, A.; Konecki, M.; Krolikowski, J.; Misiura, M.; Olszewski, M.; Pyskir, A.; Walczak, M.; Bargassa, P.; Beirão Da Cruz E Silva, C.; Calpas, B.; Di Francesco, A.; Faccioli, P.; Gallinaro, M.; Hollar, J.; Leonardo, N.; Lloret Iglesias, L.; Nemallapudi, M. V.; Seixas, J.; Toldaiev, O.; Vadruccio, D.; Varela, J.; Afanasiev, S.; Bunin, P.; Gavrilenko, M.; Golutvin, I.; Gorbunov, I.; Kamenev, A.; Karjavin, V.; Lanev, A.; Malakhov, A.; Matveev, V.; Palichik, V.; Perelygin, V.; Shmatov, S.; Shulha, S.; Skatchkov, N.; Smirnov, V.; Voytishin, N.; Zarubin, A.; Ivanov, Y.; Kim, V.; Kuznetsova, E.; Levchenko, P.; Murzin, V.; Oreshkin, V.; Smirnov, I.; Sulimov, V.; Uvarov, L.; Vavilov, S.; Vorobyev, A.; Andreev, Yu.; Dermenev, A.; Gninenko, S.; Golubev, N.; Karneyeu, A.; Kirsanov, M.; Krasnikov, N.; Pashenkov, A.; Tlisov, D.; Toropin, A.; Epshteyn, V.; Gavrilov, V.; Lychkovskaya, N.; Popov, V.; Pozdnyakov, I.; Safronov, G.; Spiridonov, A.; Stepennov, A.; Toms, M.; Vlasov, E.; Zhokin, A.; Aushev, T.; Bylinkin, A.; Chadeeva, M.; Parygin, P.; Philippov, D.; Polikarpov, S.; Popova, E.; Rusinov, V.; Andreev, V.; Azarkin, M.; Dremin, I.; Kirakosyan, M.; Terkulov, A.; Baskakov, A.; Belyaev, A.; Boos, E.; Ershov, A.; Gribushin, A.; Kaminskiy, A.; Kodolova, O.; Korotkikh, V.; Lokhtin, I.; Miagkov, I.; Obraztsov, S.; Petrushanko, S.; Savrin, V.; Snigirev, A.; Vardanyan, I.; Blinov, V.; Skovpen, Y.; Shtol, D.; Azhgirey, I.; Bayshev, I.; Bitioukov, S.; Elumakhov, D.; Kachanov, V.; Kalinin, A.; Konstantinov, D.; Krychkine, V.; Petrov, V.; Ryutin, R.; Sobol, A.; Troshin, S.; Tyurin, N.; Uzunian, A.; Volkov, A.; Adzic, P.; Cirkovic, P.; Devetak, D.; Dordevic, M.; Milosevic, J.; Rekovic, V.; Alcaraz Maestre, J.; Barrio Luna, M.; Cerrada, M.; Colino, N.; De La Cruz, B.; Delgado Peris, A.; Escalante Del Valle, A.; Fernandez Bedoya, C.; Fernández Ramos, J. P.; Flix, J.; Fouz, M. C.; Garcia-Abia, P.; Gonzalez Lopez, O.; Goy Lopez, S.; Hernandez, J. M.; Josa, M. I.; Pérez-Calero Yzquierdo, A.; Puerta Pelayo, J.; Quintario Olmeda, A.; Redondo, I.; Romero, L.; Soares, M. S.; Álvarez Fernández, A.; de Trocóniz, J. F.; Missiroli, M.; Moran, D.; Cuevas, J.; Erice, C.; Fernandez Menendez, J.; Gonzalez Caballero, I.; González Fernández, J. R.; Palencia Cortezon, E.; Sanchez Cruz, S.; Suárez Andrés, I.; Vischia, P.; Vizan Garcia, J. M.; Cabrillo, I. J.; Calderon, A.; Chazin Quero, B.; Curras, E.; Duarte Campderros, J.; Fernandez, M.; Garcia-Ferrero, J.; Gomez, G.; Lopez Virto, A.; Marco, J.; Martinez Rivero, C.; Martinez Ruiz del Arbol, P.; Matorras, F.; Piedra Gomez, J.; Rodrigo, T.; Ruiz-Jimeno, A.; Scodellaro, L.; Trevisani, N.; Vila, I.; Vilar Cortabitarte, R.; Abbaneo, D.; Auffray, E.; Baillon, P.; Ball, A. H.; Barney, D.; Bianco, M.; Bloch, P.; Bocci, A.; Botta, C.; Camporesi, T.; Castello, R.; Cepeda, M.; Cerminara, G.; Chapon, E.; Chen, Y.; d'Enterria, D.; Dabrowski, A.; Daponte, V.; David, A.; De Gruttola, M.; De Roeck, A.; Di Marco, E.; Dobson, M.; Dorney, B.; du Pree, T.; Dünser, M.; Dupont, N.; Elliott-Peisert, A.; Everaerts, P.; Franzoni, G.; Fulcher, J.; Funk, W.; Gigi, D.; Gill, K.; Glege, F.; Gulhan, D.; Gundacker, S.; Guthoff, M.; Harris, P.; Hegeman, J.; Innocente, V.; Janot, P.; Karacheban, O.; Kieseler, J.; Kirschenmann, H.; Knünz, V.; Kornmayer, A.; Kortelainen, M. J.; Krammer, M.; Lange, C.; Lecoq, P.; Lourenço, C.; Lucchini, M. T.; Malgeri, L.; Mannelli, M.; Martelli, A.; Meijers, F.; Merlin, J. A.; Mersi, S.; Meschi, E.; Milenovic, P.; Moortgat, F.; Mulders, M.; Neugebauer, H.; Orfanelli, S.; Orsini, L.; Pape, L.; Perez, E.; Peruzzi, M.; Petrilli, A.; Petrucciani, G.; Pfeiffer, A.; Pierini, M.; Racz, A.; Reis, T.; Rolandi, G.; Rovere, M.; Sakulin, H.; Schäfer, C.; Schwick, C.; Seidel, M.; Selvaggi, M.; Sharma, A.; Silva, P.; Sphicas, P.; Stakia, A.; Steggemann, J.; Stoye, M.; Tosi, M.; Treille, D.; Triossi, A.; Tsirou, A.; Veckalns, V.; Veres, G. I.; Verweij, M.; Wardle, N.; Zeuner, W. D.; Bertl, W.; Caminada, L.; Deiters, K.; Erdmann, W.; Horisberger, R.; Ingram, Q.; Kaestli, H. C.; Kotlinski, D.; Langenegger, U.; Rohe, T.; Wiederkehr, S. A.; Bachmair, F.; Bäni, L.; Berger, P.; Bianchini, L.; Casal, B.; Dissertori, G.; Dittmar, M.; Donegà, M.; Grab, C.; Heidegger, C.; Hits, D.; Hoss, J.; Kasieczka, G.; Klijnsma, T.; Lustermann, W.; Mangano, B.; Marionneau, M.; Meinhard, M. T.; Meister, D.; Micheli, F.; Musella, P.; Nessi-Tedaldi, F.; Pandolfi, F.; Pata, J.; Pauss, F.; Perrin, G.; Perrozzi, L.; Quittnat, M.; Reichmann, M.; Schönenberger, M.; Shchutska, L.; Tavolaro, V. R.; Theofilatos, K.; Vesterbacka Olsson, M. L.; Wallny, R.; Zhu, D. H.; Aarrestad, T. K.; Amsler, C.; Canelli, M. F.; De Cosa, A.; Del Burgo, R.; Donato, S.; Galloni, C.; Hreus, T.; Kilminster, B.; Ngadiuba, J.; Pinna, D.; Rauco, G.; Robmann, P.; Salerno, D.; Seitz, C.; Takahashi, Y.; Zucchetta, A.; Candelise, V.; Doan, T. H.; Jain, Sh.; Khurana, R.; Kuo, C. M.; Lin, W.; Pozdnyakov, A.; Yu, S. S.; Kumar, Arun; Chang, P.; Chao, Y.; Chen, K. F.; Chen, P. H.; Fiori, F.; Hou, W.-S.; Hsiung, Y.; Liu, Y. F.; Lu, R.-S.; Paganis, E.; Psallidas, A.; Steen, A.; Tsai, J. f.; Asavapibhop, B.; Kovitanggoon, K.; Singh, G.; Srimanobhas, N.; Adiguzel, A.; Boran, F.; Cerci, S.; Damarseckin, S.; Demiroglu, Z. S.; Dozen, C.; Dumanoglu, I.; Girgis, S.; Gokbulut, G.; Guler, Y.; Hos, I.; Kangal, E. E.; Kara, O.; Kayis Topaksu, A.; Kiminsu, U.; Oglakci, M.; Onengut, G.; Ozdemir, K.; Sunar Cerci, D.; Tali, B.; Turkcapar, S.; Zorbakir, I. S.; Zorbilmez, C.; Bilin, B.; Karapinar, G.; Ocalan, K.; Yalvac, M.; Zeyrek, M.; Gülmez, E.; Kaya, M.; Kaya, O.; Tekten, S.; Yetkin, E. A.; Agaras, M. N.; Atay, S.; Cakir, A.; Cankocak, K.; Grynyov, B.; Levchuk, L.; Sorokin, P.; Aggleton, R.; Ball, F.; Beck, L.; Brooke, J. J.; Burns, D.; Clement, E.; Cussans, D.; Davignon, O.; Flacher, H.; Goldstein, J.; Grimes, M.; Heath, G. P.; Heath, H. F.; Jacob, J.; Kreczko, L.; Lucas, C.; Newbold, D. M.; Paramesvaran, S.; Poll, A.; Sakuma, T.; Seif El Nasr-storey, S.; Smith, D.; Smith, V. J.; Belyaev, A.; Brew, C.; Brown, R. M.; Calligaris, L.; Cieri, D.; Cockerill, D. J. A.; Coughlan, J. A.; Harder, K.; Harper, S.; Olaiya, E.; Petyt, D.; Shepherd-Themistocleous, C. H.; Thea, A.; Tomalin, I. R.; Williams, T.; Auzinger, G.; Bainbridge, R.; Breeze, S.; Buchmuller, O.; Bundock, A.; Casasso, S.; Citron, M.; Colling, D.; Corpe, L.; Dauncey, P.; Davies, G.; De Wit, A.; Della Negra, M.; Di Maria, R.; Elwood, A.; Haddad, Y.; Hall, G.; Iles, G.; James, T.; Lane, R.; Laner, C.; Lyons, L.; Magnan, A.-M.; Malik, S.; Mastrolorenzo, L.; Matsushita, T.; Nash, J.; Nikitenko, A.; Palladino, V.; Pesaresi, M.; Raymond, D. M.; Richards, A.; Rose, A.; Scott, E.; Seez, C.; Shtipliyski, A.; Summers, S.; Tapper, A.; Uchida, K.; Vazquez Acosta, M.; Virdee, T.; Winterbottom, D.; Wright, J.; Zenz, S. C.; Cole, J. E.; Hobson, P. R.; Khan, A.; Kyberd, P.; Reid, I. D.; Symonds, P.; Teodorescu, L.; Turner, M.; Borzou, A.; Call, K.; Dittmann, J.; Hatakeyama, K.; Liu, H.; Pastika, N.; Smith, C.; Bartek, R.; Dominguez, A.; Buccilli, A.; Cooper, S. I.; Henderson, C.; Rumerio, P.; West, C.; Arcaro, D.; Avetisyan, A.; Bose, T.; Gastler, D.; Rankin, D.; Richardson, C.; Rohlf, J.; Sulak, L.; Zou, D.; Benelli, G.; Cutts, D.; Garabedian, A.; Hakala, J.; Heintz, U.; Hogan, J. M.; Kwok, K. H. M.; Laird, E.; Landsberg, G.; Mao, Z.; Narain, M.; Pazzini, J.; Piperov, S.; Sagir, S.; Syarif, R.; Yu, D.; Band, R.; Brainerd, C.; Burns, D.; Calderon De La Barca Sanchez, M.; Chertok, M.; Conway, J.; Conway, R.; Cox, P. T.; Erbacher, R.; Flores, C.; Funk, G.; Gardner, M.; Ko, W.; Lander, R.; Mclean, C.; Mulhearn, M.; Pellett, D.; Pilot, J.; Shalhout, S.; Shi, M.; Smith, J.; Squires, M.; Stolp, D.; Tos, K.; Tripathi, M.; Wang, Z.; Bachtis, M.; Bravo, C.; Cousins, R.; Dasgupta, A.; Florent, A.; Hauser, J.; Ignatenko, M.; Mccoll, N.; Saltzberg, D.; Schnaible, C.; Valuev, V.; Bouvier, E.; Burt, K.; Clare, R.; Ellison, J.; Gary, J. W.; Ghiasi Shirazi, S. M. A.; Hanson, G.; Heilman, J.; Jandir, P.; Kennedy, E.; Lacroix, F.; Long, O. R.; Olmedo Negrete, M.; Paneva, M. I.; Shrinivas, A.; Si, W.; Wang, L.; Wei, H.; Wimpenny, S.; Yates, B. R.; Branson, J. G.; Cittolin, S.; Derdzinski, M.; Gerosa, R.; Hashemi, B.; Holzner, A.; Klein, D.; Kole, G.; Krutelyov, V.; Letts, J.; Macneill, I.; Masciovecchio, M.; Olivito, D.; Padhi, S.; Pieri, M.; Sani, M.; Sharma, V.; Simon, S.; Tadel, M.; Vartak, A.; Wasserbaech, S.; Wood, J.; Würthwein, F.; Yagil, A.; Zevi Della Porta, G.; Amin, N.; Bhandari, R.; Bradmiller-Feld, J.; Campagnari, C.; Dishaw, A.; Dutta, V.; Franco Sevilla, M.; George, C.; Golf, F.; Gouskos, L.; Gran, J.; Heller, R.; Incandela, J.; Mullin, S. D.; Ovcharova, A.; Qu, H.; Richman, J.; Stuart, D.; Suarez, I.; Yoo, J.; Anderson, D.; Bendavid, J.; Bornheim, A.; Lawhorn, J. M.; Newman, H. B.; Nguyen, T.; Pena, C.; Spiropulu, M.; Vlimant, J. R.; Xie, S.; Zhang, Z.; Zhu, R. Y.; Andrews, M. B.; Ferguson, T.; Mudholkar, T.; Paulini, M.; Russ, J.; Sun, M.; Vogel, H.; Vorobiev, I.; Weinberg, M.; Cumalat, J. P.; Ford, W. T.; Jensen, F.; Johnson, A.; Krohn, M.; Leontsinis, S.; Mulholland, T.; Stenson, K.; Wagner, S. R.; Alexander, J.; Chaves, J.; Chu, J.; Dittmer, S.; Mcdermott, K.; Mirman, N.; Patterson, J. R.; Rinkevicius, A.; Ryd, A.; Skinnari, L.; Soffi, L.; Tan, S. M.; Tao, Z.; Thom, J.; Tucker, J.; Wittich, P.; Zientek, M.; Abdullin, S.; Albrow, M.; Apollinari, G.; Apresyan, A.; Apyan, A.; Banerjee, S.; Bauerdick, L. A. T.; Beretvas, A.; Berryhill, J.; Bhat, P. C.; Bolla, G.; Burkett, K.; Butler, J. N.; Canepa, A.; Cerati, G. B.; Cheung, H. W. K.; Chlebana, F.; Cremonesi, M.; Duarte, J.; Elvira, V. D.; Freeman, J.; Gecse, Z.; Gottschalk, E.; Gray, L.; Green, D.; Grünendahl, S.; Gutsche, O.; Harris, R. M.; Hasegawa, S.; Hirschauer, J.; Hu, Z.; Jayatilaka, B.; Jindariani, S.; Johnson, M.; Joshi, U.; Klima, B.; Kreis, B.; Lammel, S.; Lincoln, D.; Lipton, R.; Liu, M.; Liu, T.; Lopes De Sá, R.; Lykken, J.; Maeshima, K.; Magini, N.; Marraffino, J. M.; Maruyama, S.; Mason, D.; McBride, P.; Merkel, P.; Mrenna, S.; Nahn, S.; O'Dell, V.; Pedro, K.; Prokofyev, O.; Rakness, G.; Ristori, L.; Schneider, B.; Sexton-Kennedy, E.; Soha, A.; Spalding, W. J.; Spiegel, L.; Stoynev, S.; Strait, J.; Strobbe, N.; Taylor, L.; Tkaczyk, S.; Tran, N. V.; Uplegger, L.; Vaandering, E. W.; Vernieri, C.; Verzocchi, M.; Vidal, R.; Wang, M.; Weber, H. A.; Whitbeck, A.; Acosta, D.; Avery, P.; Bortignon, P.; Bourilkov, D.; Brinkerhoff, A.; Carnes, A.; Carver, M.; Curry, D.; Field, R. D.; Furic, I. K.; Konigsberg, J.; Korytov, A.; Kotov, K.; Ma, P.; Matchev, K.; Mei, H.; Mitselmakher, G.; Rank, D.; Sperka, D.; Terentyev, N.; Thomas, L.; Wang, J.; Wang, S.; Yelton, J.; Joshi, Y. R.; Linn, S.; Markowitz, P.; Rodriguez, J. L.; Ackert, A.; Adams, T.; Askew, A.; Hagopian, S.; Hagopian, V.; Johnson, K. F.; Kolberg, T.; Martinez, G.; Perry, T.; Prosper, H.; Saha, A.; Santra, A.; Yohay, R.; Baarmand, M. M.; Bhopatkar, V.; Colafranceschi, S.; Hohlmann, M.; Noonan, D.; Roy, T.; Yumiceva, F.; Adams, M. R.; Apanasevich, L.; Berry, D.; Betts, R. R.; Cavanaugh, R.; Chen, X.; Evdokimov, O.; Gerber, C. E.; Hangal, D. A.; Hofman, D. J.; Jung, K.; Kamin, J.; Sandoval Gonzalez, I. D.; Tonjes, M. B.; Trauger, H.; Varelas, N.; Wang, H.; Wu, Z.; Zhang, J.; Bilki, B.; Clarida, W.; Dilsiz, K.; Durgut, S.; Gandrajula, R. P.; Haytmyradov, M.; Khristenko, V.; Merlo, J.-P.; Mermerkaya, H.; Mestvirishvili, A.; Moeller, A.; Nachtman, J.; Ogul, H.; Onel, Y.; Ozok, F.; Penzo, A.; Snyder, C.; Tiras, E.; Wetzel, J.; Yi, K.; Blumenfeld, B.; Cocoros, A.; Eminizer, N.; Fehling, D.; Feng, L.; Gritsan, A. V.; Maksimovic, P.; Roskes, J.; Sarica, U.; Swartz, M.; Xiao, M.; You, C.; Al-bataineh, A.; Baringer, P.; Bean, A.; Boren, S.; Bowen, J.; Castle, J.; Khalil, S.; Kropivnitskaya, A.; Majumder, D.; Mcbrayer, W.; Murray, M.; Royon, C.; Sanders, S.; Schmitz, E.; Stringer, R.; Tapia Takaki, J. D.; Wang, Q.; Ivanov, A.; Kaadze, K.; Maravin, Y.; Mohammadi, A.; Saini, L. K.; Skhirtladze, N.; Toda, S.; Rebassoo, F.; Wright, D.; Anelli, C.; Baden, A.; Baron, O.; Belloni, A.; Calvert, B.; Eno, S. C.; Ferraioli, C.; Hadley, N. J.; Jabeen, S.; Jeng, G. Y.; Kellogg, R. G.; Kunkle, J.; Mignerey, A. C.; Ricci-Tam, F.; Shin, Y. H.; Skuja, A.; Tonwar, S. C.; Abercrombie, D.; Allen, B.; Azzolini, V.; Barbieri, R.; Baty, A.; Bi, R.; Brandt, S.; Busza, W.; Cali, I. A.; D'Alfonso, M.; Demiragli, Z.; Gomez Ceballos, G.; Goncharov, M.; Hsu, D.; Iiyama, Y.; Innocenti, G. M.; Klute, M.; Kovalskyi, D.; Lai, Y. S.; Lee, Y.-J.; Levin, A.; Luckey, P. D.; Maier, B.; Marini, A. C.; Mcginn, C.; Mironov, C.; Narayanan, S.; Niu, X.; Paus, C.; Roland, C.; Roland, G.; Salfeld-Nebgen, J.; Stephans, G. S. F.; Tatar, K.; Velicanu, D.; Wang, J.; Wang, T. W.; Wyslouch, B.; Benvenuti, A. C.; Chatterjee, R. M.; Evans, A.; Hansen, P.; Kalafut, S.; Kubota, Y.; Lesko, Z.; Mans, J.; Nourbakhsh, S.; Ruckstuhl, N.; Rusack, R.; Turkewitz, J.; Acosta, J. G.; Oliveros, S.; Avdeeva, E.; Bloom, K.; Claes, D. R.; Fangmeier, C.; Gonzalez Suarez, R.; Kamalieddin, R.; Kravchenko, I.; Monroy, J.; Siado, J. E.; Snow, G. R.; Stieger, B.; Alyari, M.; Dolen, J.; Godshalk, A.; Harrington, C.; Iashvili, I.; Nguyen, D.; Parker, A.; Rappoccio, S.; Roozbahani, B.; Alverson, G.; Barberis, E.; Hortiangtham, A.; Massironi, A.; Morse, D. M.; Nash, D.; Orimoto, T.; Teixeira De Lima, R.; Trocino, D.; Wood, D.; Bhattacharya, S.; Charaf, O.; Hahn, K. A.; Mucia, N.; Odell, N.; Pollack, B.; Schmitt, M. H.; Sung, K.; Trovato, M.; Velasco, M.; Dev, N.; Hildreth, M.; Hurtado Anampa, K.; Jessop, C.; Karmgard, D. J.; Kellams, N.; Lannon, K.; Loukas, N.; Marinelli, N.; Meng, F.; Mueller, C.; Musienko, Y.; Planer, M.; Reinsvold, A.; Ruchti, R.; Smith, G.; Taroni, S.; Wayne, M.; Wolf, M.; Woodard, A.; Alimena, J.; Antonelli, L.; Bylsma, B.; Durkin, L. S.; Flowers, S.; Francis, B.; Hart, A.; Hill, C.; Ji, W.; Liu, B.; Luo, W.; Puigh, D.; Winer, B. L.; Wulsin, H. W.; Benaglia, A.; Cooperstein, S.; Driga, O.; Elmer, P.; Hardenbrook, J.; Hebda, P.; Higginbotham, S.; Lange, D.; Luo, J.; Marlow, D.; Mei, K.; Ojalvo, I.; Olsen, J.; Palmer, C.; Piroué, P.; Stickland, D.; Tully, C.; Malik, S.; Norberg, S.; Barker, A.; Barnes, V. E.; Das, S.; Folgueras, S.; Gutay, L.; Jha, M. K.; Jones, M.; Jung, A. W.; Khatiwada, A.; Miller, D. H.; Neumeister, N.; Peng, C. C.; Qiu, H.; Schulte, J. F.; Sun, J.; Wang, F.; Xie, W.; Cheng, T.; Parashar, N.; Stupak, J.; Adair, A.; Akgun, B.; Chen, Z.; Ecklund, K. M.; Geurts, F. J. M.; Guilbaud, M.; Li, W.; Michlin, B.; Northup, M.; Padley, B. P.; Roberts, J.; Rorie, J.; Tu, Z.; Zabel, J.; Bodek, A.; de Barbaro, P.; Demina, R.; Duh, Y. t.; Ferbel, T.; Galanti, M.; Garcia-Bellido, A.; Han, J.; Hindrichs, O.; Khukhunaishvili, A.; Lo, K. H.; Tan, P.; Verzetti, M.; Ciesielski, R.; Goulianos, K.; Mesropian, C.; Agapitos, A.; Chou, J. P.; Gershtein, Y.; Gómez Espinosa, T. A.; Halkiadakis, E.; Heindl, M.; Hughes, E.; Kaplan, S.; Kunnawalkam Elayavalli, R.; Kyriacou, S.; Lath, A.; Montalvo, R.; Nash, K.; Osherson, M.; Saka, H.; Salur, S.; Schnetzer, S.; Sheffield, D.; Somalwar, S.; Stone, R.; Thomas, S.; Thomassen, P.; Walker, M.; Delannoy, A. G.; Foerster, M.; Heideman, J.; Riley, G.; Rose, K.; Spanier, S.; Thapa, K.; Bouhali, O.; Castaneda Hernandez, A.; Celik, A.; Dalchenko, M.; De Mattia, M.; Delgado, A.; Dildick, S.; Eusebi, R.; Gilmore, J.; Huang, T.; Kamon, T.; Mueller, R.; Pakhotin, Y.; Patel, R.; Perloff, A.; Perniè, L.; Rathjens, D.; Safonov, A.; Tatarinov, A.; Ulmer, K. A.; Akchurin, N.; Damgov, J.; De Guio, F.; Dudero, P. R.; Faulkner, J.; Gurpinar, E.; Kunori, S.; Lamichhane, K.; Lee, S. W.; Libeiro, T.; Peltola, T.; Undleeb, S.; Volobouev, I.; Wang, Z.; Greene, S.; Gurrola, A.; Janjam, R.; Johns, W.; Maguire, C.; Melo, A.; Ni, H.; Sheldon, P.; Tuo, S.; Velkovska, J.; Xu, Q.; Arenton, M. W.; Barria, P.; Cox, B.; Hirosky, R.; Ledovskoy, A.; Li, H.; Neu, C.; Sinthuprasith, T.; Sun, X.; Wang, Y.; Wolfe, E.; Xia, F.; Harr, R.; Karchin, P. E.; Sturdy, J.; Zaleski, S.; Brodski, M.; Buchanan, J.; Caillol, C.; Dasu, S.; Dodd, L.; Duric, S.; Gomber, B.; Grothe, M.; Herndon, M.; Hervé, A.; Hussain, U.; Klabbers, P.; Lanaro, A.; Levine, A.; Long, K.; Loveless, R.; Pierro, G. A.; Polese, G.; Ruggles, T.; Savin, A.; Smith, N.; Smith, W. H.; Taylor, D.; Woods, N.; CMS Collaboration

    2018-05-01

    The prompt D0 meson azimuthal anisotropy coefficients, v2 and v3, are measured at midrapidity (|y |<1.0 ) in Pb-Pb collisions at a center-of-mass energy √{sN N }=5.02 TeV per nucleon pair with data collected by the CMS experiment. The measurement is performed in the transverse momentum (pT ) range of 1 to 40 GeV /c , for central and midcentral collisions. The v2 coefficient is found to be positive throughout the pT range studied. The first measurement of the prompt D0 meson v3 coefficient is performed, and values up to 0.07 are observed for pT around 4 GeV /c . Compared to measurements of charged particles, a similar pT dependence, but smaller magnitude for pT <6 GeV /c , is found for prompt D0 meson v2 and v3 coefficients. The results are consistent with the presence of collective motion of charm quarks at low pT and a path length dependence of charm quark energy loss at high pT , thereby providing new constraints on the theoretical description of the interactions between charm quarks and the quark-gluon plasma.

  19. Surface morphology of Al0.3Ga0.7N/Al2O3-high electron mobility transistor structure.

    PubMed

    Cörekçi, S; Usanmaz, D; Tekeli, Z; Cakmak, M; Ozçelik, S; Ozbay, E

    2008-02-01

    We present surface properties of buffer films (AIN and GaN) and Al0.3Gao.zN/Al2O3-High Electron Mobility Transistor (HEMT) structures with/without AIN interlayer grown on High Temperature (HT)-AIN buffer/Al2O3 substrate and Al2O3 substrate. We have found that the GaN surface morphology is step-flow in character and the density of dislocations was about 10(8)-10(9) cm(-2). The AFM measurements also exhibited that the presence of atomic steps with large lateral step dimension and the surface of samples was smooth. The lateral step sizes are in the range of 100-250 nm. The typical rms values of HEMT structures were found as 0.27, 0.30, and 0.70 nm. HT-AIN buffer layer can have a significant impact on the surface morphology of Al0.3Ga0.7N/Al2O3-HEMT structures.

  20. Frequency of pathogenic germline mutation in CHEK2, PALB2, MRE11, and RAD50 in patients at high risk for hereditary breast cancer.

    PubMed

    Kim, Haeyoung; Cho, Dae-Yeon; Choi, Doo Ho; Oh, Mijin; Shin, Inkyung; Park, Won; Huh, Seung Jae; Nam, Seok Jin; Lee, Jeong Eon; Kim, Seok Won

    2017-01-01

    This study was performed to evaluate the frequency of mutations in CHEK2, PALB2, MRE11, and RAD50 among Korean patients at high risk for hereditary breast cancer. A total of 235 Korean patients with hereditary breast cancer who tested negative for BRCA1/2 mutation were enrolled to this study. Entire coding regions of CHEK2, PALB2, MRE11, and RAD50 were analyzed using massively parallel sequencing (MPS). Sequence variants detected by MPS were confirmed by Sanger sequencing. Six patients (2.5 %) were found to have pathogenic variants in CHEK2 (n = 1), PALB2 (n = 2), MRE11 (n = 1), and RAD50 (n = 2). Among the pathogenic variants, PALB2 c.2257C>T was previously reported in other studies, while CHEK2 c.1245dupC, PALB2 c.1048C>T, MRE11 c.1773_1774delAA, RAD50 c.1276C>T, and RAD50 c.3811_3813delGAA were newly identified in this study. A total of 15 missense variants were found in the four genes among 26 patients; 7 patients had a variant in CHEK2, 11 in PALB2, 2 in MRE11, and 6 in RAD50. When in silico analyses were performed to the 15 missense variants, six variants (CHEK2 c.686A>G, PALB2 c.1492G>T, PALB2 c.3054G>C, MRE11 c.140C>T, RAD50 c.1456C>T, and RAD50 c.3790C>T) were predicted to be deleterious. Pathogenic variants in CHEK2, PALB2, MRE11, and RAD50 were detected in a small proportion of Korean patients with features of hereditary breast cancer.

  1. Effect of CHEK2 missense variant I157T on the risk of breast cancer in carriers of other CHEK2 or BRCA1 mutations.

    PubMed

    Cybulski, C; Górski, B; Huzarski, T; Byrski, T; Gronwald, J; Debniak, T; Wokolorczyk, D; Jakubowska, A; Serrano-Fernández, P; Dork, T; Narod, S A; Lubinski, J

    2009-02-01

    Carriers of heterozygous mutations in CHEK2 or BRCA1 are at increased risk of breast cancer. These mutations are rare and a very small number of women in a population will carry two mutations. However, it is of interest to estimate the breast cancer risks associated with carrying two mutations because this information may be informative for genetic counsellors and may provide clues to the carcinogenic process. We genotyped 7782 Polish breast cancer patients and 6233 controls for seven founder mutations in BRCA1 and CHEK2. Odds ratios (OR) and 95% confidence intervals (CI) were estimated for the mutations, singly and in combination. Of the 7782 women with breast cancer, 1091 had one mutation (14.0%) and 37 had two mutations (0.5%). Compared to controls, the odds ratio for a BRCA1 mutation in isolation was 13.1 (95% CI 8.2 to 21). The odds ratio was smaller for BRCA1 mutation carriers who also carried a CHEK2 mutation (OR 6.6, 95% CI 1.5 to 29), but the difference was not statistically significant. In contrast, the odds ratio for women who carried two CHEK2 mutations (OR 3.9, 95% CI 1.5 to 10) was greater than that for women who carried one CHEK2 mutation (OR 1.9, 95% CI 1.6 to 2.1). The odds ratio for women who carried both a truncating mutation and the missense mutation in CHEK2 was 7.0 (95% CI 0.9 to 56) and was greater than for women who carried the truncating mutation alone (OR 3.3, 95% CI 2.4 to 4.3) or the missense mutation alone (OR 1.6, 95% CI 1.4 to 1.9), but the difference was not statistically significant. Our study suggests that the risk of breast cancer in carriers of a deleterious CHEK2 mutation is increased if the second allele is the I157T missense variant. However, the presence of a CHEK2 mutation in women with a BRCA1 mutation may not increase their risk beyond that of the BRCA1 mutation alone. These suggestive findings need to be verified in other studies.

  2. Elevated preoperative neutrophil-to-lymphocytes ratio predicts poor prognosis after esophagectomy in T1 esophageal cancer.

    PubMed

    Nakamura, Kenichi; Yoshida, Naoya; Baba, Yoshifumi; Kosumi, Keisuke; Uchihara, Tomoyuki; Kiyozumi, Yuki; Ohuchi, Mayuko; Ishimoto, Takatsugu; Iwatsuki, Masaaki; Sakamoto, Yasuo; Watanabe, Masayuki; Baba, Hideo

    2017-06-01

    The neutrophil-to-lymphocyte ratio (NLR) has been reported to predict the prognosis of various malignant tumors, including esophageal cancer. However, no previous reports have supported the use of the preoperative NLR as an independent prognostic marker focused on superficial (T1) esophageal cancer. The aim of this study was to elucidate the prognostic impact of the preoperative NLR in T1 esophageal cancer. This retrospective study recruited 245 consecutive patients with T1 esophageal cancer who underwent subtotal esophagectomy between 2005 and 2016. The relationship between the preoperative NLR and clinicopathological characteristics was analyzed. The preoperative NLR was significantly higher in male patients (p = 0.029), patients with T1b esophageal cancer (p = 0.0274), and patients with venous vessel invasion (p = 0.0082). In the Kaplan-Meier analysis, the elevated preoperative NLR was significantly associated with a poorer disease-free survival (p < 0.0001) and overall survival (p = 0.0004). In the multivariate Cox model, the elevated preoperative NLR was an independent prognostic marker for both disease-free survival (p = 0.0013) and overall survival (p = 0.0027). An elevated preoperative NLR predicts poor prognosis in T1 esophageal cancer, suggesting the utility of the NLR as an easily measurable and generally available independent prognostic marker.

  3. Adjuvant therapy sparing in rectal cancer achieving complete response after chemoradiation

    PubMed Central

    García-Albéniz, Xabier; Gallego, Rosa; Hofheinz, Ralf Dieter; Fernández-Esparrach, Gloria; Ayuso-Colella, Juan Ramón; Bombí, Josep Antoni; Conill, Carles; Cuatrecasas, Miriam; Delgado, Salvadora; Ginés, Angels; Miquel, Rosa; Pagés, Mario; Pineda, Estela; Pereira, Verónica; Sosa, Aarón; Reig, Oscar; Victoria, Iván; Feliz, Luis; María de Lacy, Antonio; Castells, Antoni; Burkholder, Iris; Hochhaus, Andreas; Maurel, Joan

    2014-01-01

    AIM: To evaluate the long-term results of conventional chemoradiotherapy and laparoscopic mesorectal excision in rectal adenocarcinoma patients without adjuvant therapy. METHODS: Patients with biopsy-proven adenocarcinoma of the rectum staged cT3-T4 by endoscopic ultrasound or magnetic resonance imaging received neoadjuvant continuous infusion of 5-fluorouracil for five weeks and concomitant radiotherapy. Laparoscopic surgery was planned after 5-8 wk. Patients diagnosed with ypT0N0 stage cancer were not treated with adjuvant therapy according to the protocol. Patients with ypT1-2N0 or ypT3-4 or N+ were offered 5-fluorouracil-based adjuvant treatment on an individual basis. An external cohort was used as a reference for the findings. RESULTS: One hundred and seventy six patients were treated with induction chemoradiotherapy and 170 underwent total mesorectal excision. Cancer staging of ypT0N0 was achieved in 26/170 (15.3%) patients. After a median follow-up of 58.3 mo, patients with ypT0N0 had five-year disease-free and overall survival rates of 96% (95%CI: 77-99) and 100%, respectively. We provide evidence about the natural history of patients with localized rectal cancer achieving a complete response after preoperative chemoradiation. The inherent good prognosis of these patients will have implications for clinical trial design and care of patients. CONCLUSION: Withholding adjuvant chemotherapy after complete response following standard neoadjuvant chemoradiotherapy and laparoscopic mesorectal excision might be safe within an experienced multidisciplinary team. PMID:25400468

  4. Pressure-tuned superconductivity and normal-state behavior in Ba ( Fe 0.943 Co 0.057 ) 2 As 2 near the antiferromagnetic boundary

    DOE PAGES

    Liu, W.; Wu, Y. F.; Li, X. J.; ...

    2018-04-23

    Superconductivity in iron pnictides is unconventional and pairing may be mediated by magnetic fluctuations in the Fe sublattice. Pressure is a clean method to explore superconductivity in iron based superconductors by tuning the ground state continuously without introducing disorder. Here we present a systematic high pressure transport study in Ba (Fe 1 - xCo x) 2 As 2 single crystals with x = 0.057, which is near the antiferromagnetic instability. Resistivity ρ = ρ 0 + AT n was studied under applied pressure up to 7.90 GPa. The parameter n approaches a minimum value of n ≈ 1 at amore » critical pressure P c = 3.65 GPa. Near P c, the superconducting transition temperature T c reaches a maximum value of 25.8 K. In addition, the superconducting diamagnetism at 2 K shows a sudden change around the same critical pressure. Finally, these results may be associated with a possible quantum critical point hidden inside the superconducting dome, near optimum T c.« less

  5. Pressure-tuned superconductivity and normal-state behavior in Ba ( Fe 0.943 Co 0.057 ) 2 As 2 near the antiferromagnetic boundary

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Liu, W.; Wu, Y. F.; Li, X. J.

    Superconductivity in iron pnictides is unconventional and pairing may be mediated by magnetic fluctuations in the Fe sublattice. Pressure is a clean method to explore superconductivity in iron based superconductors by tuning the ground state continuously without introducing disorder. Here we present a systematic high pressure transport study in Ba (Fe 1 - xCo x) 2 As 2 single crystals with x = 0.057, which is near the antiferromagnetic instability. Resistivity ρ = ρ 0 + AT n was studied under applied pressure up to 7.90 GPa. The parameter n approaches a minimum value of n ≈ 1 at amore » critical pressure P c = 3.65 GPa. Near P c, the superconducting transition temperature T c reaches a maximum value of 25.8 K. In addition, the superconducting diamagnetism at 2 K shows a sudden change around the same critical pressure. Finally, these results may be associated with a possible quantum critical point hidden inside the superconducting dome, near optimum T c.« less

  6. Melanoma Staging: Evidence-Based Changes in the American Joint Committee on Cancer Eighth Edition Cancer Staging Manual

    PubMed Central

    Gershenwald, Jeffrey E.; Scolyer, Richard A.; Hess, Kenneth R.; Sondak, Vernon K.; Long, Georgina V.; Ross, Merrick I.; Lazar, Alexander J.; Faries, Mark B.; Kirkwood, John M.; McArthur, Grant A.; Haydu, Lauren E.; Eggermont, Alexander M. M.; Flaherty, Keith T.; Balch, Charles M.; Thompson, John F.

    2018-01-01

    To update the melanoma staging system of the American Joint Committee on Cancer (AJCC) a large database was assembled comprising >46,000 patients from 10 centers worldwide with stages I, II, and III melanoma diagnosed since 1998. Based on analyses of this new database, the existing seventh edition AJCC stage IV database, and contemporary clinical trial data, the AJCC Melanoma Expert Panel introduced several important changes to the Tumor, Nodes, Metastasis (TNM) classification and stage grouping criteria. Key changes in the eighth edition AJCC Cancer Staging Manual include: 1) tumor thickness measurements to be recorded to the nearest 0.1 mm, not 0.01 mm; 2) definitions of T1a and T1b are revised (T1a, <0.8 mm without ulceration; T1b, 0.8–1.0 mm with or without ulceration or <0.8 mm with ulceration), with mitotic rate no longer a T category criterion; 3) pathological (but not clinical) stage IA is revised to include T1b N0 M0 (formerly pathologic stage IB); 4) the N category descriptors “microscopic” and “macroscopic” for regional node metastasis are redefined as “clinically occult” and “clinically apparent”; 5) prognostic stage III groupings are based on N category criteria and T category criteria (ie, primary tumor thickness and ulceration) and increased from 3 to 4 subgroups (stages IIIA–IIID); 6) definitions of N subcategories are revised, with the presence of microsatellites, satellites, or in-transit metastases now categorized as N1c, N2c, or N3c based on the number of tumor-involved regional lymph nodes, if any; 7) descriptors are added to each M1 subcategory designation for lactate dehydrogenase (LDH) level (LDH elevation no longer upstages to M1c); and 8) a new M1d designation is added for central nervous system metastases. This evidence-based revision of the AJCC melanoma staging system will guide patient treatment, provide better prognostic estimates, and refine stratification of patients entering clinical trials. PMID:29028110

  7. Movement of the Epiglottis in Mammals

    DTIC Science & Technology

    1993-01-01

    dysphagia . Arch. Otolaryngol. 109:376-380. Ekberg, 0. and S.V. Sigurjonsson (1982) Movement of the epiglottis during deglutition. Gastrointest...children : Preliminary observations. Dysphagia . 4:112-117. Koenig, J.S., A.M. Davies and B.T. Thach (1990) Coordination of breathing, sucking, and...Arndorfer (1990) Coordination of deglutitive glottic closure with oropharyngeal swallowing. Gastroenterology . 98:478-1484. Siegel, S. and N. J. Castellan

  8. Abdominopelvic 1.5-T and 3.0-T MR Imaging in Healthy Volunteers: Relationship to Formation of DNA Double-Strand Breaks.

    PubMed

    Suntharalingam, Saravanabavaan; Mladenov, Emil; Sarabhai, Theresia; Wetter, Axel; Kraff, Oliver; Quick, Harald H; Forsting, Michael; Iliakis, Georg; Nassenstein, Kai

    2018-05-01

    Purpose To investigate the relationship between abdominopelvic magnetic resonance (MR) imaging and formation of DNA double-strand breaks (DSBs) in peripheral blood lymphocytes among a cohort of healthy volunteers. Materials and Methods Blood samples were obtained from 40 healthy volunteers (23 women and 17 men; mean age, 27.2 years [range, 21-37 years]) directly before and 5 and 30 minutes after abdominopelvic MR imaging performed at 1.5 T (n = 20) or 3.0 T (n = 20). The number of DNA DSBs in isolated blood lymphocytes was quantified after indirect immunofluorescent staining of a generally accepted DSB marker, γ-H2AX, by means of high-throughput automated microscopy. As a positive control of DSB induction, blood lymphocytes from six volunteers were irradiated in vitro with x-rays at a dose of 1 Gy (70-90 keV). Statistical analysis was performed by using a Friedman test. Results No significant alteration in the frequency of DNA DSB induction was observed after MR imaging (before imaging: 0.22 foci per cell, interquartile range [IQR] = 0.54 foci per cell; 5 minutes after MR imaging: 0.08 foci per cell, IQR = 0.39 foci per cell; 30 minutes after MR imaging: 0.09 foci per cell, IQR = 0.63 foci per cell; P = .057). In vitro radiation of lymphocytes with 1 Gy led to a significant increase in DSBs (0.22 vs 3.43 foci per cell; P = .0312). The frequency of DSBs did not differ between imaging at 1.5 T and at 3.0 T (5 minutes after MR imaging: 0.23 vs 0.06 foci per cell, respectively [P = .57]; 30 minutes after MR imaging: 0.12 vs 0.08 foci per cell [P = .76]). Conclusion Abdominopelvic MR imaging performed at 1.5 T or 3.0 T does not affect the formation of DNA DSBs in peripheral blood lymphocytes. © RSNA, 2018.

  9. Association Between N-acetyltransferase 2 Polymorphism and Bladder Cancer Risk: Results From Studies of the Past Decade and a Meta-Analysis.

    PubMed

    Wu, Haoran; Wang, Xugang; Zhang, Liang; Mo, Naixin; Lv, Zhong

    2016-04-01

    Numerous studies have identified that the slow acetylation status of N-acetyltransferase 2 (NAT2) is associated with an elevated bladder cancer risk. However, the results remain inconclusive. The aim of our study was to evaluate the effect of NAT2 acetylation status in patients with bladder cancer. Electronic databases were searched to retrieve related studies published in the past decade. The pooled odds ratio (OR) with its 95% confidence interval (CI) was used to calculate the strength of this relationship. Overall, a total of 18 studies were selected for the analysis, which included 4473 bladder cancer cases and 7204 matched controls. Our result showed that the NAT2 slow acetylation phenotypes were significantly associated with an increased risk of bladder cancer compared with the rapid phenotypes (OR, 1.56; 95% CI, 1.33-1.82; P < .00001) in a random-effect model. This significant association was also found in a subgroup analysis of ethnicity (P < .05). Furthermore, the NAT2 slow phenotypes also significantly increased the risk of bladder cancer in smokers (OR, 0.75; 95% CI, 0.62-0.90; P = .002). However, no correlation was found between the combined effect of NAT2 slow phenotypes and gender with bladder cancer risk (OR, 0.89; 95% CI, 0.28-2.78; P = .84). In conclusion, our results suggest that the NAT2 slow acetylator, in particular, the NAT2 slow acetylator combined with smoking, are associated with an increased bladder cancer risk. Future well-designed studies with large populations and more ethnicities are needed to clarify this association further. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. A study of T2-weighted MR image texture features and diffusion-weighted MR image features for computer-aided diagnosis of prostate cancer

    NASA Astrophysics Data System (ADS)

    Peng, Yahui; Jiang, Yulei; Antic, Tatjana; Giger, Maryellen L.; Eggener, Scott; Oto, Aytekin

    2013-02-01

    The purpose of this study was to study T2-weighted magnetic resonance (MR) image texture features and diffusionweighted (DW) MR image features in distinguishing prostate cancer (PCa) from normal tissue. We collected two image datasets: 23 PCa patients (25 PCa and 23 normal tissue regions of interest [ROIs]) imaged with Philips MR scanners, and 30 PCa patients (41 PCa and 26 normal tissue ROIs) imaged with GE MR scanners. A radiologist drew ROIs manually via consensus histology-MR correlation conference with a pathologist. A number of T2-weighted texture features and apparent diffusion coefficient (ADC) features were investigated, and linear discriminant analysis (LDA) was used to combine select strong image features. Area under the receiver operating characteristic (ROC) curve (AUC) was used to characterize feature effectiveness in distinguishing PCa from normal tissue ROIs. Of the features studied, ADC 10th percentile, ADC average, and T2-weighted sum average yielded AUC values (+/-standard error) of 0.95+/-0.03, 0.94+/-0.03, and 0.85+/-0.05 on the Phillips images, and 0.91+/-0.04, 0.89+/-0.04, and 0.70+/-0.06 on the GE images, respectively. The three-feature combination yielded AUC values of 0.94+/-0.03 and 0.89+/-0.04 on the Phillips and GE images, respectively. ADC 10th percentile, ADC average, and T2-weighted sum average, are effective in distinguishing PCa from normal tissue, and appear robust in images acquired from Phillips and GE MR scanners.

  11. Life course evolution of body size and breast cancer survival in the E3N cohort.

    PubMed

    His, Mathilde; Le Guélennec, Marine; Mesrine, Sylvie; Boutron-Ruault, Marie-Christine; Clavel-Chapelon, Françoise; Fagherazzi, Guy; Dossus, Laure

    2018-04-15

    Although adult obesity has been associated with poor breast cancer survival, data on adiposity at different periods in life and its lifelong evolution are scarce. Our aims were to assess the associations between breast cancer survival and body size during childhood, puberty and early adulthood and body size trajectories from childhood to adulthood. Self-assessed body size at age 8, at puberty, at age 20-25 and at age 35-40 and trajectories of body size of 4,662 breast cancer survivors from the prospective E3N cohort were studied in relation to risk of death from any cause, death from breast cancer and second invasive cancer event using multivariate Cox regression models. Four trajectories of body size were identified (T1 "moderate increase," T2 "stable/low increase," T3 "increase at puberty" and T4 "constantly high"). Compared with stable body size, an increase in body size during adult life was associated with an increased risk of death from any cause (HR T1 vs. T2 = 1.27; 95% CI = 1.01-1.60) and an increased risk of second invasive cancer event (HR T1 vs. T2 = 1.25; 95% CI = 1.06-1.47). Silhouettes at various ages were not associated with survival. Our results suggest that the evolution of body size from childhood to adulthood has a long-term influence on breast cancer survival. Although these results need to be confirmed, this work sheds light on the need to combine lifelong approaches to current BMI to better identify breast cancer survivors who are at higher risk of recurrence or second primary cancer, or of death. © 2017 UICC.

  12. Effects of hydrostatic pressure and biaxial strains on the elastic and electronic properties of t-C8B2N2

    NASA Astrophysics Data System (ADS)

    Zhu, Haiyan; Shi, Liwei; Li, Shuaiqi; Duan, Yifeng; Zhang, Shaobo; Xia, Wangsuo

    2018-04-01

    The effects of hydrostatic pressure and biaxial strains on the elastic and electronic properties of a superhard material t-C8B2N2 have been studied using first-principles calculations. The structure is proven to be mechanically and dynamically stable under the applied external forces. All the elastic constants (except C66) and elastic modulus increase (decrease) with increasing pressure and compressive (tensile) biaxial strain ɛxx. A microscopic model is used to calculate the Vicker's hardness of every single bond as well as the crystal. The hardness of t-C8B2N2 (64.7 GPa) exceeds that of c-BN (62 GPa) and increases obviously by employing pressure and compressive ɛxx. Furthermore, the Debye temperature and anisotropy of sound velocities for t-C8B2N2 have been discussed. t-C8B2N2 undergoes an indirect to direct bandgap transition when ɛxx > 2%; however, the indirect bandgap character of the material remains under pressure.

  13. γδ T cells as a potential tool in colon cancer immunotherapy.

    PubMed

    Ramutton, Thiranut; Buccheri, Simona; Dieli, Francesco; Todaro, Matilde; Stassi, Giorgio; Meraviglia, Serena

    2014-01-01

    γδ T cells are capable of recognizing tumor cells and exert potent cellular cytotoxicity against a large range of tumors, including colon cancer. However, tumors utilize numerous strategies to escape recognition or killing by patrolling γδ T cells, such a downregulation of NKG2D ligands, MICA/B and ULBPs. Therefore, the combined upregulation of T-cell receptorand NKG2D ligands on tumor cells and induction of NKG2D expression on γδ T cells may greatly enhance tumor killing and unlock the functions of γδ T cells. Here, we briefly review current data on the mechanisms of γδ T-cell recognition and killing of colon cancer cells and propose that γδ T cells may represent a promising target for the design of novel and highly innovative immunotherapy in patients with colon cancer.

  14. Influence of the vocal cord mobility in salvage surgery after radiotherapy for early-stage squamous cell carcinoma of the glottic larynx.

    PubMed

    Gorphe, Philippe; Blanchard, Pierre; Temam, Stephane; Janot, François

    2015-10-01

    Disease relapses occur in up to 40% of cases after radiotherapy (RT) for early-stage glottic laryngeal neoplasms, and the foremost remaining treatment option is salvage total laryngectomy (STL). Our objectives were to review the outcomes of patients treated with salvage surgery after RT for early-stage carcinoma of the glottic larynx and to assess prognostic factors. We retrospectively analyzed 43 patients who underwent surgery. Overall and disease-free survival rates among subgroups were calculated and compared, stratified by preoperative stage, vocal cord mobility and postoperative histopathologic data. Recurrences occurred 22.7 months after the end of RT. Surgery was STL in 33 cases (76.8%). The main prognostic factors associated with survival rates were initial vocal cord mobility, vocal cord mobility at the diagnosis of recurrence, and changes in mobility. Vocal cord mobility is an important clinical criterion in treatment decision making for early-stage glottis carcinoma and remains important during follow-up.

  15. Tumor-Associated Macrophages and Regulatory T Cells Infiltration and the Clinical Outcome in Colorectal Cancer.

    PubMed

    Waniczek, Dariusz; Lorenc, Zbigniew; Śnietura, Mirosław; Wesecki, Mariusz; Kopec, Agnieszka; Muc-Wierzgoń, Małgorzata

    2017-10-01

    The aim of the study is the assessment of the intensity of the infiltration of tumor-associated macrophages (TAMs) CD68 + /iNOS - and Tregs CD8 + /FoxP3 + in colorectal cancer (CRC) patients as prognostic factors with respect to disease-free survival (DFS) and overall survival (OS). In this retrospective study, tissue samples were obtained from 89 patients undergoing resection for CRC (stage IIA, pT3N0M0 and stages IIIB and IIIC, pT3N1-2M0). Recurrence was observed in 45 patients at the time of the follow-up (10 local recurrences, 35 distant metastases). In patients with recurrence the following were present: a tendency to an older average age at the time of diagnosis (p = 0.07), higher nodal involvement (p = 0.002) and more advanced clinical disease (p = 0.01). The analysis of the clinical data and immunohistochemical studies were performed with the methodology of identification of TAM and Treg subsets in histological sections, with the aim to use it in routine clinical management. Both DSF and OS were the clinical parameters assessed in the study. The presence of intense infiltration of TAMs in the tumor stroma was related to shorter DFS (p = 0.005) and OS (p = 0.006). The opposite tendency was observed in the tumor front (p = 0.061). The relative risks of recurrence and cancer-related death were more than twice higher in the group of patients with intense infiltration of TAMs in the tumor stroma (RR 2.05, 95% CI 1.33-3.14; p = 0.001 and RR 2.08, 95% CI 1.28-3.39; p = 0.003, respectively). Intense infiltration of Tregs in the tumor stroma was related to shorter DFS and OS (p < 0.0001). The relative risks of recurrence and death in a group of patients with intense infiltration of Tregs in the tumor stroma were more than 12 times higher than in patients with less intense infiltration (RR 12.3, 95% CI 5.44-27.9; p < 0.0001 and RR 12.5, 95% CI 4.9-32.4; p < 0.0001, respectively). Infiltration of TAMs CD68 + /iNOS - and

  16. Isotropic three-dimensional T2 mapping of knee cartilage: Development and validation.

    PubMed

    Colotti, Roberto; Omoumi, Patrick; Bonanno, Gabriele; Ledoux, Jean-Baptiste; van Heeswijk, Ruud B

    2018-02-01

    1) To implement a higher-resolution isotropic 3D T 2 mapping technique that uses sequential T 2 -prepared segmented gradient-recalled echo (Iso3DGRE) images for knee cartilage evaluation, and 2) to validate it both in vitro and in vivo in healthy volunteers and patients with knee osteoarthritis. The Iso3DGRE sequence with an isotropic 0.6 mm spatial resolution was developed on a clinical 3T MR scanner. Numerical simulations were performed to optimize the pulse sequence parameters. A phantom study was performed to validate the T 2 estimation accuracy. The repeatability of the sequence was assessed in healthy volunteers (n = 7). T 2 values were compared with those from a clinical standard 2D multislice multiecho (MSME) T 2 mapping sequence in knees of healthy volunteers (n = 13) and in patients with knee osteoarthritis (OA, n = 5). The numerical simulations resulted in 100 excitations per segment and an optimal radiofrequency (RF) excitation angle of 15°. The phantom study demonstrated a good correlation of the technique with the reference standard (slope 0.9 ± 0.05, intercept 0.2 ± 1.7 msec, R 20.99). Repeated measurements of cartilage T 2 values in healthy volunteers showed a coefficient of variation of 5.6%. Both Iso3DGRE and MSME techniques found significantly higher cartilage T 2 values (P < 0.03) in OA patients. Iso3DGRE precision was equal to that of the MSME T 2 mapping in healthy volunteers, and significantly higher in OA (P = 0.01). This study successfully demonstrated that high-resolution isotropic 3D T 2 mapping for knee cartilage characterization is feasible, accurate, repeatable, and precise. The technique allows for multiplanar reformatting and thus T 2 quantification in any plane of interest. 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:362-371. © 2017 International Society for Magnetic Resonance in Medicine.

  17. [The role of ¹⁸F-FDG PET/CT for detecting nodal metastases in cN0 head neck cancer patients:a Meta-analysis].

    PubMed

    Li, X Y; Sun, C L; Du, X D

    2018-05-01

    Objective: The aim of this study is to evaluate the accuracy of ¹⁸F-fluorodeoxyglucose PET/CT(¹⁸F-FDG PET/CT) for the diagnosis of cervical node metastases in cN0 head neck cancer patients. Method: An electronic database search(PubMed,EMBASE,Cochrane Library,WanFang and CNKI databases)was performed. Updated quality assessment of diagnostic accuracy studies-2(QUADAS-2) was used to assess study quality. Data analyses were performed with Meta-Disc1.4. Result: Eight studies were included in the present Meta-analysis. For patient-specific data,the pooled sensitivity,specificity,diagnostic odds ratio(DOR),positive likelihood ratio(PLR),and negative likelihood(NLR)for ¹⁸F-FDG PET/CT were 0.61(95% CI 0.52-0.69),0.74(95% CI 0.68-0.78),9.62(95% CI 2.49-37.22),3.22(95% CI 1.55-6.71),and 0.42(95% CI 0.24-0.37),respectively. The area under the curve(AUC)was 0.804 1.The evaluation of heterogeneity,calculated the pooled diagnostic odds ratio,gave a Q value of 21.26( P <0.05)and an I²of 81.2%. Conclusion: The results of meta-analysis suggested that ¹⁸F-FDG PET/CT did not provide better diagnostic accuracy than CT/MRI in detecting cervical node metastases in cN0 head and neck cancer. Considering the high heterogeneity of the included studies,potential value of PET/CT needs to be validated in future studies. Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.

  18. 2MASS J20261584-2943124: an Unresolved L0.5 + T6 Spectral Binary

    NASA Astrophysics Data System (ADS)

    Gelino, Christopher R.; Burgasser, Adam J.

    2010-07-01

    We identify the L dwarf 2MASS J20261584-2943124 as an unresolved spectral binary, based on low-resolution, near-infrared spectroscopy from IRTF/SpeX. The data reveal a peculiar absorption feature at 1.6 μm, previously noted in the spectra of other very low-mass spectral binaries, which likely arises from overlapping FeH and CH4 absorption bands in the blended light of an L dwarf/T dwarf pair. Spectral template matching analysis indicates component types of L0.5 and T6, with relative brightness ΔH = 4.2 ± 0.6. Laser guide star adaptive optics imaging observations with Keck/NIRC2 fail to resolve the source, indicating a maximum separation at the observing epoch of 0farcs25, or a projected separation of 9 AU assuming a distance of 36 ± 5 pc. With an age that is likely to be relatively older (gsim5 Gyr) based on the system's large V tan and mass ratio arguments, the relative motion of the potentially "massive" (0.06-0.08 M sun) components of 2MASS J2026-2943 may be detectable through radial velocity variations, like its earlier-type counterpart 2MASS J03202839-0446358 (M8+T5), providing dynamical mass measurements that span the hydrogen burning limit. Some of the data presented herein were obtained at the W. M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California, and the National Aeronautics and Space Administration. The Observatory was made possible by the generous financial support of the W. M. Keck Foundation.

  19. 20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years.

    PubMed

    Pan, Hongchao; Gray, Richard; Braybrooke, Jeremy; Davies, Christina; Taylor, Carolyn; McGale, Paul; Peto, Richard; Pritchard, Kathleen I; Bergh, Jonas; Dowsett, Mitch; Hayes, Daniel F

    2017-11-09

    The administration of endocrine therapy for 5 years substantially reduces recurrence rates during and after treatment in women with early-stage, estrogen-receptor (ER)-positive breast cancer. Extending such therapy beyond 5 years offers further protection but has additional side effects. Obtaining data on the absolute risk of subsequent distant recurrence if therapy stops at 5 years could help determine whether to extend treatment. In this meta-analysis of the results of 88 trials involving 62,923 women with ER-positive breast cancer who were disease-free after 5 years of scheduled endocrine therapy, we used Kaplan-Meier and Cox regression analyses, stratified according to trial and treatment, to assess the associations of tumor diameter and nodal status (TN), tumor grade, and other factors with patients' outcomes during the period from 5 to 20 years. Breast-cancer recurrences occurred at a steady rate throughout the study period from 5 to 20 years. The risk of distant recurrence was strongly correlated with the original TN status. Among the patients with stage T1 disease, the risk of distant recurrence was 13% with no nodal involvement (T1N0), 20% with one to three nodes involved (T1N1-3), and 34% with four to nine nodes involved (T1N4-9); among those with stage T2 disease, the risks were 19% with T2N0, 26% with T2N1-3, and 41% with T2N4-9. The risk of death from breast cancer was similarly dependent on TN status, but the risk of contralateral breast cancer was not. Given the TN status, the factors of tumor grade (available in 43,590 patients) and Ki-67 status (available in 7692 patients), which are strongly correlated with each other, were of only moderate independent predictive value for distant recurrence, but the status regarding the progesterone receptor (in 54,115 patients) and human epidermal growth factor receptor type 2 (HER2) (in 15,418 patients in trials with no use of trastuzumab) was not predictive. During the study period from 5 to 20 years, the

  20. In vitro bio-functional performances of the novel superelastic beta-type Ti-23Nb-0.7Ta-2Zr-0.5N alloy.

    PubMed

    Ion, Raluca; Gordin, Doina-Margareta; Mitran, Valentina; Osiceanu, Petre; Dinescu, Sorina; Gloriant, Thierry; Cimpean, Anisoara

    2014-02-01

    The materials used for internal fracture fixations and joint replacements are mainly made of metals which still face problems ranging from higher rigidity than that of natural bone to leaching cytotoxic metallic ions. Beta (β)-type titanium alloys with low elastic modulus made from non-toxic and non-allergenic elements are desirable to reduce stress shielding effect and enhance bone remodeling. In this work, a new β-type Ti-23Nb-0.7Ta-2Zr-0.5N alloy with a Young's modulus of approximately 50 GPa was designed and characterized. The behavior of MC3T3-E1 pre-osteoblasts on the new alloy, including adhesion, proliferation and differentiation, was evaluated by examining the cytoskeleton, focal adhesion formation, metabolic activity and extracellular matrix mineralization. Results indicated that the pre-osteoblast cells exhibited a similar degree of attachment and growth on Ti-23Nb-0.7Ta-2Zr-0.5N and Ti-6Al-4V. However, the novel alloy proved to be significantly more efficient in sustaining mineralized matrix deposition upon osteogenic induction of the cells than Ti-6Al-4V control. Further, the analysis of RAW 264.7 macrophages cytokine gene and protein expression indicated no significant inflammatory response. Collectively, these findings suggest that the Ti-23Nb-0.7Ta-2Zr-0.5N alloy, which has an increased mechanical biocompatibility with bone, allows a better osteogenic differentiation of osteoblast precursor cells than Ti-6Al-4V and holds great potential for future clinical prosthetic applications. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Thiols decrease cytokine levels and down-regulate the expression of CD30 on human allergen-specific T helper (Th) 0 and Th2 cells

    PubMed Central

    Bengtsson, Å; Lundberg, M; Avila-Cariño, J; Jacobsson, G; Holmgren, A; Scheynius, A

    2001-01-01

    The thiol antioxidant N-acetyl-l-cysteine (NAC), known as a precursor of glutathione (GSH), is used in AIDS treatment trials, as a chemoprotectant in cancer chemotherapy and in treatment of chronic bronchitis. In vitro, GSH and NAC are known to enhance T cell proliferation, production of IL-2 and up-regulation of the IL-2 receptor. The 120-kD CD30 surface antigen belongs to the tumour necrosis factor (TNF) receptor superfamily. It is expressed by activated T helper (Th) cells and its expression is sustained in Th2 cells. We have analysed the effect of GSH and NAC on the cytokine profile and CD30 expression on human allergen-specific T cell clones (TCC). TCC were stimulated with anti-CD3 antibodies in the presence of different concentrations of GSH and NAC. Both thiols caused a dose dependent down-regulation of IL-4, IL-5 and IFN-γ levels in Th0 and Th2 clones, with the most pronounced decrease of IL-4. Furthermore, they down-regulated the surface expression of CD30, and the levels of soluble CD30 (sCD30) in the culture supernatants were decreased. In contrast, the surface expression of CD28 or CD40 ligand (CD40L) was not significantly changed after treatment with 20 mm NAC. These results indicate that GSH and NAC favour a Th1 response by a preferential down-regulation of IL-4. In addition, the expression of CD30 was down regulated by GSH and NAC, suggesting that CD30 expression is dependent on IL-4, or modified by NAC. In the likely event that CD30 and its soluble counterpart prove to contribute to the pathogenesis in Th2 related diseases such as allergy, NAC may be considered as a future therapeutic agent in the treatment of these diseases. PMID:11298119

  2. Patients with metastatic breast cancer leading to CD4+ T cell lymphopaenia have poor outcome.

    PubMed

    Trédan, Olivier; Manuel, Manuarii; Clapisson, Gilles; Bachelot, Thomas; Chabaud, Sylvie; Bardin-dit-Courageot, Christine; Rigal, Chantal; Biota, Cathy; Bajard, Agathe; Pasqual, Nicolas; Blay, Jean-Yves; Caux, Christophe; Ménétrier-Caux, Christine

    2013-05-01

    Low lymphocyte count is a prognostic factor in cancer patients including metastatic breast cancer patients (MBC) but the relative role of each lymphocyte subtype is unclear in MBC. The impact of lymphocyte subsets was analysed in two prospective MBC patients' cohorts. Cohort A patients (n=103) were included before the first line of chemotherapy and cohort B patients (n=101) were included after at least one line of chemotherapy. Extensive phenotypic analyses were performed on fresh whole blood. Plasma cytokines levels were measured using commercially available Luminex-based multiplex kits. Prognostic value of lymphocyte subsets and circulating cytokines was analysed. In both cohorts, severe lymphopaenia (<0.7 Giga/L) correlated with poor overall survival (OS) (median OS: 6.6 months versus 21.7 months in cohort A and 4.5 versus 9 months in cohort B). CD8(+), CD19(+) and CD56(+) T cell counts had no significant prognostic value for OS. After stratification (≤0.2, [0.20-0.45], >0.45 Giga/L), CD4 lymphopaenia appeared to be correlated with poor OS in both cohorts. Furthermore, severe CD4(+) lymphopaenia (≤0.2 Giga/L) was strongly correlated with poor OS in both cohorts (1.2 months versus 24.9 months in cohort A and 5.7 versus 13.1 months in cohort B). In multivariate analysis, after stratification CD4(+) lymphopaenia appeared to be an independent prognostic factor for OS in both cohorts. CD4(+) lymphopaenia correlated with low plasmatic levels of CCL22 that might directly contribute to CD4(+) lymphopaenia. CD4(+) lymphopaenia was associated with reduced OS in MBC patients regardless of the chemotherapy line. Decreased levels of plasmatic CCL22 may contribute to CD4(+) lymphopaenia. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Boosting the SNR by adding a receive-only endorectal monopole to an external antenna array for high-resolution, T2 -weighted imaging of early-stage cervical cancer with 7-T MRI.

    PubMed

    van Kalleveen, I M L; Hoogendam, J P; Raaijmakers, A J E; Visser, F; Arteaga de Castro, C S; Verheijen, R H M; Luijten, P R; Zweemer, R P; Veldhuis, W B; Klomp, D W J

    2017-09-01

    The aim of this study was to investigate the signal-to-noise ratio (SNR) gain in early-stage cervical cancer at ultrahigh-field MRI (e.g. 7 T) using a combination of multiple external antennas and a single endorectal antenna. In particular, we used an endorectal monopole antenna to increase the SNR in cervical magnetic resonance imaging (MRI). This should allow high-resolution, T 2 -weighted imaging and magnetic resonance spectroscopy (MRS) for metabolic staging, which could facilitate the local tumor status assessment. In a prospective feasibility study, five healthy female volunteers and six patients with histologically proven stage IB1-IIB cervical cancer were scanned at 7 T. We used seven external fractionated dipole antennas for transmit-receive (transceive) and an endorectally placed monopole antenna for reception only. A region of interest, containing both normal cervix and tumor tissue, was selected for the SNR measurement. Separated signal and noise measurements were obtained in the region of the cervix for each element and in the near field of the monopole antenna (radius < 30 mm) to calculate the SNR gain of the endorectal antenna in each patient. We obtained high-resolution, T 2 -weighted images with a voxel size of 0.7 × 0.8 × 3.0 mm 3 . In four cases with optimal placement of the endorectal antenna (verified on the T 2 -weighted images), a mean gain of 2.2 in SNR was obtained at the overall cervix and tumor tissue area. Within a radius of 30 mm from the monopole antenna, a mean SNR gain of 3.7 was achieved in the four optimal cases. Overlap between the two different regions of the SNR calculations was around 24%. We have demonstrated that the use of an endorectal monopole antenna substantially increases the SNR of 7-T MRI at the cervical anatomy. Combined with the intrinsically high SNR of ultrahigh-field MRI, this gain may be employed to obtain metabolic information using MRS and to enhance spatial resolutions to assess tumor invasion

  4. The in vivo Therapeutic Effect of Free Wanderer Powder (逍 遙 散 xiāo yáo sǎn, Xiaoyaosan) on Mice with 4T1 Cell Induced Breast Cancer Model

    PubMed Central

    Chen, Wen-Fang; Xu, Li; Yu, Chung-Him; Ho, Chui-Kwan; Wu, Ka; Leung, Gina CW; Wong, Man-Sau

    2012-01-01

    In the present study, we investigated the therapeutic effect of a classical TCM formula, Free Wanderer Powder (逍遙散 xiāo yáo sǎn), in a breast cancer mouse model induced with estrogen-insensitive breast cancer 4T1 cells. Ovariectomized Balb/c mice (6-8 weeks) or sham mice were injected into the fourth mammary fat pad with 4T1 cells in which tumors were palpable 7 days after injection. On the eighth day, the mice were divided into 4 groups and tubefed daily with vehicle, Free Wanderer Powder (逍遙散 xiāo yáo sǎn) formula or tamoxifen for 28 days. Tumor growth inhibition and the decrease of the average tumor mass were most evident in mice treated with Free Wanderer Powder (逍遙散 xiāo yáo sǎn). Free Wanderer Powder (逍遙散 xiāo yáo sǎn) treatment significantly reduced Bcl-2 and elevated Bax and p53 protein expressions in breast cancer tumor. These results were further confirmed by immunohistochemisty. Tamoxifen could decrease spleen mass and Bcl-2 protein expression, increase the Bax protein expression as well as exert uterotrophic effects by increasing uterus index and inducing the gene expressions in the uterus. Taken together, these results show that Free Wanderer Powder (逍遙散 xiāo yáo sǎn) treatment induced apoptosis at protein level and inhibited the tumor growth in 4T1-induced ovariectomized Balb/c female mice, indicating the possibility of its future use for treatment of estrogen-insensitive breast caner. PMID:24716117

  5. Evaluation of peripheral blood T lymphocyte surface activation markers and transcription factors in patients with early stage non-small cell lung cancer.

    PubMed

    Rutkowski, Jacek; Cyman, Marta; Ślebioda, Tomasz; Bemben, Kamila; Rutkowska, Aleksandra; Gruchała, Marcin; Kmieć, Zbigniew; Pliszka, Agnieszka; Zaucha, Renata

    2017-12-01

    Lung cancer cells harboring multiple mutations as a consequence of long-term damage by different etiologic factors are responsible for high immunogenicity. Immune checkpoint inhibitors significantly improve treatment results in non-small cell lung cancer (NSCLC). Unfortunately, the role of T-lymphocytes in early NSCLC has not been sufficiently elucidated. The aim of this study was to characterize peripheral blood T cells expressing several selected surface antigens (CD4, CD8, CD25, CD28, PD-1, CTLA-4) and transcription factors (T-bet, ROR-yt, Fox-P3, GATA-3) in this patient population. The study group (LC) consisted of 80 treatment-naïve patients with T1/2aN0M0 NSCLC and was compared with 40 cancer-free patients matched for non-oncological diseases and demographic parameters (CG). Significantly higher counts of CTLA-4+cells (in both CD4+and CD8+subtypes), a lower proportion of PD-1 expressing cells and a significantly higher percentage of Fox-P3+CD4+cells were found in the LC group. The high proportion of CD4+PD-1+cells significantly correlated with poor outcomes in LC group, while low CD4/CD8 ratio predicted a better prognosis. Based on our results it seems that NSCLC even at early stages of development initiate changes in the proportions of T cells that may have a significant impact on the clinical outcome. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Methylenetetrahydrofolate reductase C677T polymorphism in patients with lung cancer in a Korean population

    PubMed Central

    2011-01-01

    Background This study was designed to investigate an association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and the risk of lung cancer in a Korean population. Methods We conducted a large-scale, case-control study involving 3938 patients with newly diagnosed lung cancer and 1700 healthy controls. Genotyping was performed with peripheral blood DNA for MTHFR C677T polymorphisms. Statistical significance was estimated by logistic regression analysis. Results The MTHFR C677T frequencies of CC, CT, and TT genotypes were 34.5%, 48.5%, and 17% among lung cancer patients, and 31.8%, 50.7%, and 17.5% in the controls, respectively. The MTHFR 677CT and TT genotype showed a weak protection against lung cancer compared with the homozygous CC genotype, although the results did not reach statistical significance. The age- and gender-adjusted odds ratio (OR) of overall lung cancer was 0.90 (95% confidence interval (CI), 0.77-1.04) for MTHFR 677 CT and 0.88 (95% CI, 0.71-1.07) for MTHFR 677TT. However, after stratification analysis by histological type, the MTHFR 677CT genotype showed a significantly decreased risk for squamous cell carcinoma (age- and gender-adjusted OR, 0.78; 95% CI, 0.64-0.96). The combination of 677 TT homozygous with 677 CT heterozygous also appeared to have a protection effect on the risk of squamous cell carcinoma. We observed no significant interaction between the MTHFR C677T polymorphism and age and gender or smoking habit. Conclusions This is the first reported study focusing on the association between MTHFR C677T polymorphisms and the risk of lung cancer in a Korean population. The T allele was found to provide a weak protective association with lung squamous cell carcinoma. PMID:21342495

  7. NExT: Advancing Promising Cancer Therapies

    Cancer.gov

    The NCI Experimental Therapeutics (NExT) program works with researchers and top scientific experts to advance promising or novel cancer therapies from the earliest stages of research to clinical trials. Learn about recent successes from NExT in this Cancer Currents blog post.

  8. 26 CFR 301.6103(n)-2T - Disclosure of return information in connection with written contracts among the IRS...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... (temporary). 301.6103(n)-2T Section 301.6103(n)-2T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF... Returns Returns and Records § 301.6103(n)-2T Disclosure of return information in connection with written...) General rule. (1) Pursuant to the provisions of sections 6103(n) and 7623 of the Internal Revenue Code and...

  9. Co-Introduced Functional CCR2 Potentiates In Vivo Anti-Lung Cancer Functionality Mediated by T Cells Double Gene-Modified to Express WT1-Specific T-Cell Receptor

    PubMed Central

    Asai, Hiroaki; Fujiwara, Hiroshi; An, Jun; Ochi, Toshiki; Miyazaki, Yukihiro; Nagai, Kozo; Okamoto, Sachiko; Mineno, Junichi; Kuzushima, Kiyotaka; Shiku, Hiroshi; Inoue, Hirofumi; Yasukawa, Masaki

    2013-01-01

    Background and Purpose Although gene-modification of T cells to express tumor-related antigen-specific T-cell receptor (TCR) or chimeric antigen receptor (CAR) has clinically proved promise, there still remains room to improve the clinical efficacy of re-directed T-cell based antitumor adoptive therapy. In order to achieve more objective clinical responses using ex vivo-expanded tumor-responsive T cells, the infused T cells need to show adequate localized infiltration into the tumor. Methodology/Principal Findings Human lung cancer cells variously express a tumor antigen, Wilms' Tumor gene product 1 (WT1), and an inflammatory chemokine, CCL2. However, CCR2, the relevant receptor for CCL2, is rarely expressed on activated T-lymphocytes. A HLA-A2402+ human lung cancer cell line, LK79, which expresses high amounts of both CCL2 and WT1 mRNA, was employed as a target. Normal CD8+ T cells were retrovirally gene-modified to express both CCR2 and HLA-A*2402-restricted and WT1235–243 nonapeptide-specific TCR as an effector. Anti-tumor functionality mediated by these effector cells against LK79 cells was assessed both in vitro and in vivo. Finally the impact of CCL2 on WT1 epitope-responsive TCR signaling mediated by the effector cells was studied. Introduced CCR2 was functionally validated using gene-modified Jurkat cells and human CD3+ T cells both in vitro and in vivo. Double gene-modified CD3+ T cells successfully demonstrated both CCL2-tropic tumor trafficking and cytocidal reactivity against LK79 cells in vitro and in vivo. CCL2 augmented the WT1 epitope-responsive TCR signaling shown by relevant luciferase production in double gene-modified Jurkat/MA cells to express luciferase and WT1-specific TCR, and CCL2 also dose-dependently augmented WT1 epitope-responsive IFN-γ production and CD107a expression mediated by these double gene-modifiedCD3+ T cells. Conclusion/Significance Introduction of the CCL2/CCR2 axis successfully potentiated in vivo anti-lung cancer

  10. Comparison of 7.0- and 3.0-T MRI and MRA in ischemic-type moyamoya disease: preliminary experience.

    PubMed

    Deng, Xiaofeng; Zhang, Zihao; Zhang, Yan; Zhang, Dong; Wang, Rong; Ye, Xun; Xu, Long; Wang, Bo; Wang, Kai; Zhao, Jizong

    2016-06-01

    OBJECT The authors compared the image quality and diagnostic sensitivity and specificity of 7.0-T and 3.0-T MRI and time-of-flight (TOF) MR angiography (MRA) in patients with moyamoya disease (MMD). METHODS MR images of 15 patients with ischemic-type MMD (8 males, 7 females; age 13-48 years) and 13 healthy controls (7 males, 6 females; age 19-28 years) who underwent both 7.0-T and 3.0-T MRI and MRA were studied retrospectively. The main intracranial arteries were assessed by using the modified Houkin's grading system (MRA score). Moyamoya vessels (MMVs) were evaluated by 2 grading systems: the MMV quality score and the MMV area score. Two diagnostic criteria for MMD were used: the T2 criteria, which used flow voids in the basal ganglion on T2-weighted images, and the TOF criteria, which used the high-intensity areas in the basal ganglion on source images from TOF MRA. All data were evaluated by 2 independent readers who were blinded to the strength field and presence or absence of MMD. Using conventional angiography as the gold standard, the sensitivity and specificity of 7.0-T and 3.0-T MRI/MRA in the diagnosis of MMD were calculated. The differences between 7.0-T and 3.0-T MRI and MRA were statistically compared. RESULTS No significant differences were observed between 7.0-T and 3.0-T MRA in MRA score (p = 0.317) or MRA grade (p = 0.317). There was a strong correlation between the Suzuki's stage and MRA grade in both 3.0-T (rs = 0.930; p < 0.001) and 7.0-T (rs = 0.966; p < 0.001) MRA. However, MMVs were visualized significantly better on 7.0-T than on 3.0-T MRA, suggested by both the MMV quality score (p = 0.001) and the MMV area score (p = 0.001). The correlation between the Suzuki's stage and the MMV area score was moderate in 3.0-T MRA (rs = 0.738; p = 0.002) and strong in 7.0-T MRA (rs = 0.908; p < 0.001). Moreover, 7.0-T MR images showed a greater capacity for detecting flow voids in the basal ganglion on both T2-weighted MR images (p < 0.001) and TOF source

  11. Changes of electronic properties of p-GaN(0 0 0 1) surface after low-energy N+-ion bombardment

    NASA Astrophysics Data System (ADS)

    Grodzicki, M.; Mazur, P.; Ciszewski, A.

    2018-05-01

    The p-GaN(0 0 0 1) crystal with a relatively low acceptor concentration of 5 × 1016 cm-3 is used in these studies, which are carried out in situ under ultrahigh vacuum (UHV) by ultraviolet photoelectron spectroscopy (UPS), X-ray photoelectron spectroscopy (XPS) and low-energy electron diffraction (LEED). The p-GaN(0 0 0 1)-(1 × 1) surface is achieved by thermal cleaning. N+-ion bombardment by a 200 eV ion beam changes the surface stoichiometry, enriches it with nitrogen, and disorders it. Such modified surface layer inverts its semiconducting character from p- into n-type. The electron affinity for the already cleaned p-GaN surface and that just after bombardment shows a shift from 2.2 eV to 3.2 eV, as well as an increase of band bending at the vacuum/surface interface from 1.4 eV to 2.5 eV. Proper post-bombardment heating of the sample restores the initial atomic order of the modified layer, leaving its n-type semiconducting character unchanged. The results of the measurements are discussed based on two types of surface states concepts.

  12. Neuropathic symptoms, quality of life, and clinician perception of patient care in medical oncology outpatients with colorectal, breast, lung, and prostate cancer.

    PubMed

    Jones, Desiree; Zhao, Fengmin; Brell, Joanna; Lewis, Mark A; Loprinzi, Charles L; Weiss, Matthias; Fisch, Michael J

    2015-03-01

    We investigated how treatment-induced neuropathic symptoms are associated with patients' quality of life (QOL) and clinician-reported difficulty in caring for patients. Data were obtained from 3,106 outpatients with colorectal, breast, lung, or prostate cancer on numbness/tingling (N/T), neuropathic pain, and QOL. Clinicians reported the degree of difficulty in caring for patients' physical and psychological symptoms. For all patients, moderate to severe N/T was associated with poor QOL (OR = 1.82, 95% CI = 1.47-2.26, P < 0.001) but neuropathic pain was not (OR = 1.31, 95% CI = 0.94-1.83, P = 0.114). Moderate to severe N/T and neuropathic pain were associated with increased care difficulty (OR = 1.49, 95% CI = 1.27-1.74, P < 0.001 for N/T, and OR = 1.46, 95% CI = 1.15-1.84, P = 0.002 for neuropathic pain). The association of neuropathic pain with care difficulty was most significant in patients with colorectal cancer (CRC) (OR = 2.32, 95% CI = 1.41-3.83, P = 0.001). Baseline neuropathic pain was associated with declining QOL in CRC patients (OR = 2.08, 95% CI = 1.21-3.58, P = 0.008). Clinicians may experience increased care difficulty for patients of all cancer types with moderate to severe N/T or neuropathic pain; care difficulty due to neuropathic pain may be higher for CRC patients. Nearly half the patients of all cancer types with moderate to severe N/T may expect poor short-term QOL; CRC-but not other-patients with baseline neuropathic pain are likely to experience declining QOL. About half of patients with moderate to severe N/T (any cancer type) may expect poor QOL in the short term; CRC patients with baseline neuropathic pain in particular may experience declining QOL.

  13. Significance of Cox-2 expression in rectal cancers with or without preoperative radiotherapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Pachkoria, Ketevan; Zhang Hong; Adell, Gunnar

    2005-11-01

    Purpose: Radiotherapy has reduced local recurrence of rectal cancers, but the result is not satisfactory. Further biologic factors are needed to identify patients for more effective radiotherapy. Our aims were to investigate the relationship of cyclooxygenase-2 (Cox-2) expression to radiotherapy, and clinicopathologic/biologic variables in rectal cancers with or without radiotherapy. Methods and Materials: Cox-2 expression was immunohistochemically examined in distal normal mucosa (n = 28), in adjacent normal mucosa (n = 107), in primary cancer (n = 138), lymph node metastasis (n = 30), and biopsy (n = 85). The patients participated in a rectal cancer trial of preoperative radiotherapy.more » Results: Cox-2 expression was increased in primary tumor compared with normal mucosa (p < 0.0001), but there was no significant change between primary tumor and metastasis. Cox-2 positivity was or tended to be related to more p53 and Ki-67 expression, and less apoptosis (p {<=} 0.05). In Cox-2-negative cases of either biopsy (p = 0.01) or surgical samples (p = 0.02), radiotherapy was related to less frequency of local recurrence, but this was not the case in Cox-2-positive cases. Conclusion: Cox-2 expression seemed to be an early event involved in rectal cancer development. Radiotherapy might reduce a rate of local recurrence in the patients with Cox-2 weakly stained tumors, but not in those with Cox-2 strongly stained tumors.« less

  14. Prostate-specific Antigen (PSA) Density and Free to Total PSA Ratio in Diagnosing Prostate Cancer with Prostate-Specific Antigen Levels of 4.0 ng/ml or Less.

    PubMed

    Liu, Xin; Tang, Jie; Fei, Xiang; Li, Qiu-Yang

    2015-11-01

    We aimed to value the usefulness of free to total prostate-specific antigen and Prostate-specific antigen (PSA) density for prostate cancer in the patients with PSA levels of 4.0 ng/ml or less. A total of 343 subjects with PSA levels of 4.0 ng/ml or less were biopsied. All patients were divided into four groups according to the PSA levels: 0 to 1.0 ng/ml, 1.1 to 2.0 ng/ml, 2.1 to 3.0 ng/ml, and 3.1 to 4.0 ng/ml. The reliability of cancer detection in relation to the f/t PSA ratio and PSAD were estimated. Overall, 65 people were diagnosed with prostate cancer. The detection rate was 16.28%、17.17%, 21.82%, 25.00% in subjects with PSA levels of 0 to 1.0 ng/ml, 1.1 to 2.0 ng/ml, 2.1 to 3.0 ng/ml, and 3.1 to 4.0 ng/ml, respectively. The f/t PSA ratio was significantly lower in patients with prostate cancer and PSA levels of 2.1 to 4.0 ng/ml (P<0.05). The PSAD had no statistical significance between the two groups. Routine prostate biopsy should be undertaken if the f/t PSA ratio less than 15% with /without abnormal DRE/TRUS findings.

  15. Ethnic sensitivity assessment of the antibody-drug conjugate trastuzumab emtansine (T-DM1) in patients with HER2-positive locally advanced or metastatic breast cancer.

    PubMed

    Li, Chunze; Wang, Bei; Lu, Dan; Jin, Jin Y; Gao, Yuying; Matsunaga, Kiyoshi; Igawa, Yuriko; Nijem, Ihsan; Lu, Michael; Strasak, Alexander; Chernyukhin, Nataliya; Girish, Sandhya

    2016-09-01

    Trastuzumab emtansine (T-DM1) is indicated for previously treated HER2-positive metastatic breast cancer. Ethnic sensitivity assessment of T-DM1 was conducted using data from eight clinical studies to ensure that the clinically recommended dose is appropriate across ethnicities. Four approaches were used: (1) non-compartmental analysis (NCA) comparing pharmacokinetic parameters of T-DM1 and relevant analytes across ethnic groups, (2) population pharmacokinetic (popPK) analysis assessing the impact of ethnicity on pharmacokinetics, (3) comparison of T-DM1 pharmacokinetics in Japanese patients versus the global population, and (4) exposure-response analyses assessing the impact of ethnicity on safety and efficacy. NCA pharmacokinetic parameters (T-DM1, total trastuzumab, DM1) were comparable across ethnic groups; mean cycle 1 T-DM1 AUCinf was 475, 442, and 518 day µg/mL for white (n = 461), Asian (n = 68), and others (n = 57), respectively. PopPK analysis showed that ethnicity (white, Asian, and others) was not a significant covariate for T-DM1 pharmacokinetics (n = 671). Additionally, visual predictive check plots indicated that observed pharmacokinetic profiles in Japanese patients (n = 42) were within the prediction interval generated from the final PopPK model. Exposure-response analyses showed that ethnicity was not a significant covariate impacting efficacy or hepatotoxicity risk, but there was a trend of greater thrombocytopenia risk among Asians versus non-Asians, which could not be explained by similar exposure between the ethnic groups. Most Asians with thrombocytopenia were able to continue T-DM1 using dose-adjustment rules recommended for the global population. These results suggest that T-DM1 pharmacokinetics are comparable across ethnic groups and that use of the current dosing regimen is appropriate across ethnicities.

  16. T2-weighted four dimensional magnetic resonance imaging with result-driven phase sorting

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Liu, Yilin; Yin, Fang-Fang; Cai, Jing, E-mail: jing.cai@duke.edu

    2015-08-15

    Purpose: T2-weighted MRI provides excellent tumor-to-tissue contrast for target volume delineation in radiation therapy treatment planning. This study aims at developing a novel T2-weighted retrospective four dimensional magnetic resonance imaging (4D-MRI) phase sorting technique for imaging organ/tumor respiratory motion. Methods: A 2D fast T2-weighted half-Fourier acquisition single-shot turbo spin-echo MR sequence was used for image acquisition of 4D-MRI, with a frame rate of 2–3 frames/s. Respiratory motion was measured using an external breathing monitoring device. A phase sorting method was developed to sort the images by their corresponding respiratory phases. Besides, a result-driven strategy was applied to effectively utilize redundantmore » images in the case when multiple images were allocated to a bin. This strategy, selecting the image with minimal amplitude error, will generate the most representative 4D-MRI. Since we are using a different image acquisition mode for 4D imaging (the sequential image acquisition scheme) with the conventionally used cine or helical image acquisition scheme, the 4D dataset sufficient condition was not obviously and directly predictable. An important challenge of the proposed technique was to determine the number of repeated scans (N{sub R}) required to obtain sufficient phase information at each slice position. To tackle this challenge, the authors first conducted computer simulations using real-time position management respiratory signals of the 29 cancer patients under an IRB-approved retrospective study to derive the relationships between N{sub R} and the following factors: number of slices (N{sub S}), number of 4D-MRI respiratory bins (N{sub B}), and starting phase at image acquisition (P{sub 0}). To validate the authors’ technique, 4D-MRI acquisition and reconstruction were simulated on a 4D digital extended cardiac-torso (XCAT) human phantom using simulation derived parameters. Twelve healthy volunteers were

  17. The cocrystal rac-1-[(N,4-dimethylbenzenesulfonamido)methyl]-2-(diphenylphosphoryl)ferrocene-rac-1-[(N,4-dimethylbenzenesulfonamido)methyl]-2-(diphenylphosphanyl)ferrocene (0.45/0.55).

    PubMed

    Wei, Muh Mei; Audin, Catherine; Manoury, Eric; Deydier, Eric; Daran, Jean Claude

    2014-03-01

    As part of our interest in the synthesis and catalytic applications of chiral (diphenylphosphanyl)ferrocene ligands, we designed a number of P,N-containing ligands for use in asymmetric transfer hydrogenation (ATH). During the synthetic procedure to obtain rac-1-[(N,4-dimethylbenzenesulfonamido)methyl]-2-(diphenylphosphanyl)ferrocene, the title compound, [Fe(C5H5)(C26H25NO2PS)]0.55 · [Fe(C5H5)(C26H25NO3PS)]0.45, was obtained as a by-product. It is composed of a ferrocene group disubstituted by a partially oxidized diphenylphosphanyl group, as confirmed by (31)P NMR analysis, and an (N,4-dimethylbenzenesulfonamido)methyl substituent. Owing to the partially oxidized diphenylphosphanyl group, it is best to view the crystal as being composed of a mixture of non-oxidized and oxidized phosphane, so it can be regarded as a cocrystal. It is also a racemate. To the best of our knowledge, the P=O distance [1.344 (4) Å] is the shortest observed for related (diphenylphosphoryl)ferrocene compounds. The packing is stabilized by weak C-H...O interactions, forming R2(2)(10) hydrogen-bonding motifs, which build up a chain along the c axis.

  18. Role of Adjuvant Treatment in Esophageal Cancer With Incidental Pathologic Node Positivity.

    PubMed

    Gao, Sarah J; Park, Henry S; Corso, Christopher D; Rutter, Charles E; Kim, Anthony W; Johung, Kimberly L

    2017-07-01

    The optimal adjuvant treatment for cT1-2 N0 esophageal cancer patients found to have pathologic nodal involvement after an upfront operation is unclear. This study investigated the effects of postoperative chemotherapy and chemoradiation therapy on overall survival in cT1-2 N0 patients with incidental pN + disease stratified by margin status. We identified cT1-2 N0 M0 esophageal carcinoma patients from 2004 to 2012 from the National Cancer Data Base. Patients were categorized as having received surgical resection alone, surgical resection followed by chemotherapy (S+CT), and surgical resection followed by concurrent chemoradiation therapy (S+CRT). Subset analyses were conducted on margin-negative and margin-positive patients. Overall survival was compared by Kaplan-Meier estimation, the log-rank test, and multivariable Cox regression analysis. Among 443 patients, 52.6% received surgical resection alone, 18.7% received S+CT, and 28.6% received S+CRT. Significantly more adenocarcinoma patients received adjuvant treatment (50.8%) than squamous cell carcinoma patients (27.7%, p = 0.001). On multivariable analysis, S+CT (hazard ratio, 0.64; 95% confidence interval, 0.45 to 0.91; p = 0.014) and S+CRT (hazard ratio, 0.73; 95% confidence interval,. 0.55 to 0.98; p = 0.038) both were associated with significantly increased overall survival. These findings persisted among margin-negative patients. However, in margin-positive patients, S+CRT (hazard ratio, 0.29; p = 0.002) was the only treatment arm that was associated with significantly improved survival compared with surgical resection alone. Among cT1-2 N0 pN + esophageal cancer patients, adjuvant chemotherapy may be sufficient for margin-negative patients, whereas adjuvant chemoradiation therapy appears necessary for margin-positive patients. Further prospective studies are needed to confirm the results. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  19. [Clinicopathological characteristics and prognostic factor analysis of carcinoma in remnant stomach cancer at Peking University Cancer Hospital].

    PubMed

    Wang, Yinkui; Li, Ziyu; Jin, Chenggen; Ying, Xiangji; Gao, Chao; Wang, Yuchen; Xiao, Qiyan; Zhang, Yan; Chen, Yufan; Zhang, Lianhai; Ji, Jiafu

    2018-05-25

    To investigate the interval time to canceration, clinicopathological characteristics and prognostic factors of carcinoma in remnant stomach (CRS) in patients with primary benign diseases or primary malignant tumors. Based on the criteria of the definition of CRS proposed by Japanese Gastric Cancer Association in 2017, a retrospective analysis was conducted on clinicopathological characteristics of patients diagnosed with CRS at Peking University Cancer Hospital from March 1992 to March 2017. Between patients with primary benign diseases (CBS-B group) and primary malignant tumors (CBS-M group), continuous variables were compared using the Student's t-test or the Mann-Whitney U test; categorical variables were compared using the chi-square test or Fisher's exact test. Spearmen-Rho was used to examine correlation. Survival was estimated and compared using Kaplan-Meier methods. Cox proportional hazards regression was applied to identify independent prognostic factors. Area under ROC curve(AUC) was used to evaluate and compare prediction accuracy. A total of 89 patients were included in the study with a male: female ratio of 5.4 to 1.0. The male: female ratio in CRS-B (n=46) and CRS-M (n=43) group was 14.3 to 1.0 and 2.9 to 1.0 respectively with significant difference (χ 2 =6.091, P=0.019). The interval time to canceration in CRS-B and CRS-M group was 342(36-576) months and 47(12-360) months respectively with significant difference (t=8.887, P=0.000). The interval time to canceration was correlated with the first operative procedure in CRS-B group (r=0.398, P=0.006), while interval time to canceration was correlated with the age at the first operation in CRS-M group (r=0.337, P=0.027). After differentiating the pathological findings of the first operative sample and the second operative sample, 27 patients presented recurrence and 15 patients had new cancer, and the corresponding interval time to canceration was 46(12-132) months and 60(12-360) months respectively with

  20. Comparative differences between T1a/b and T1e/m as substages in T1 urothelial carcinoma of the bladder.

    PubMed

    Turan, Turgay; Efiloğlu, Özgür; Günaydin, Bilal; Özkanli, Şeyma; Nikerel, Emrah; Atiş, Gökhan; Çaşkurlu, Turhan; Yildirim, Asif

    2018-01-01

    To evaluate the prognostic value of the depth of lamina propria invasion in patients with T1 bladder cancer and to display comparative differences between the T1a/b and T1e/m substaging systems. This study included 106 patients with primary stage T1 urothelial bladder tumours who underwent surgery between January 2009 and December 2014. Pathologic specimens were re-evaluated to confirm the diagnosis of T1 and substaging by the same pathologist using two systems: T1a and T1b, and T1m and T1e. Age, tumour size, multiplicity, associated carcinoma in situ, tumour grade, and T1 substaging system were investigated to detect the relation between disease progression and recurrence. The recurrence rate was 52% for T1a (n=42) vs. 76% for T1b (n=20) (p=0.028) and 55% for T1m (n=32) vs. 62% for T1e (n=30), respectively (p=0.446). There was no significant difference between the substaging groups for disease progression: T1a (n=12, 15%) vs. T1b (n=7, 27%), and T1m (n=8, 13.8%) vs. T1e (n=11, 23%) (p>0.05). In the multivariate analysis, tumour size >3 cm (p=0.008), multiplicity (p=0.049), and substaging T1b (p=0.043) were independent predictive factors for tumour recurrence. According to the Kaplan-Meier actuarial method, recurrence-free survival was significantly different in patients with pT1a tumours compared with those with pT1b tumours (p=0.033). Substaging T1 provides a prediction of disease recurrence. Regarding recurrence, T1a/b substaging can provide better knowledge of disease behaviour because it is predicted as more superior than T1 m/e, and it can help in determining the requirement for early cystectomy. Copyright® by the International Brazilian Journal of Urology.