Science.gov

Sample records for advanced cervix carcinoma

  1. Organ preservation in locally advanced carcinoma of the uterine cervix.

    PubMed

    Smaniotto, D; Andrulli, A D; Tortoreto, F; Niespolo, R M; Valentini, V

    1997-01-01

    In the treatment of locally advanced carcinoma of the uterine cervix the multimodal therapeutic approach is useful to improve overall survival and disease-free survival. Two studies of concomitant radiochemotherapy were conducted. In the first, recurrences of gynecologic tumors were treated, in the second primary tumors of the uterine cervix. In the first study 29 patients, of whom 15 with endometrial cancer recurrence, 10 with cervical cancer recurrence and 4 with vulvar cancer recurrence were treated with FUMIR schedule (5-FU and mitomycin C plus concomitant radiotherapy to the pelvis in two cycles of 23.4 Gy) and subsequent brachytherapy boost. In the second study 17 patients, of whom 14 evaluable, were treated with external beam radiotherapy (ERT 40 Gy) and concomitant chemotherapy (5-FU and CDDP). Before and after treatment the patients were examined with MRI. After radiochemotherapy radical hysterectomy and histology of surgical specimen was performed. Results of first study were as follows: acute G1-G2 (RTOG) hematologic toxicity 56%, G3 4%; G1-G2 gastrointestinal 54%, G1-G2 skin 29%; G1-G2 rectum 24%; G1-G2 bladder 25%; G1-G2 vagina 30%. Local control, overall survival and disease-free survival at 24 months were 45%, 76% and 67%, respectively. Results of the second study showed 9/14 patients with complete response and 4/4 patients with partial response (93%), no change in 1, with 100% MRI accuracy as compared to histology. Based on these results a phase III clinical trial was planned in primary cancer of the uterine cervix using concomitant radiochemotherapy (CDDP + 5-FU) plus intracavitary brachytherapy for organ preservation.

  2. Locally advanced adenocarcinoma and adenosquamous carcinomas of the cervix compared to squamous cell carcinomas of the cervix in Gynecologic Oncology Group trials of cisplatin-based chemoradiation

    PubMed Central

    Rose, Peter G; Java, James J; Whitney, Charles W.; Stehman, Frederick B; Lanciano, Rachelle; Thomas, Gillian M

    2015-01-01

    Objective Conflicting results have been reported for adeno- and adenosquamous carcinomas of the cervix with respect to their response to therapy and prognosis. The current study sought to evaluate impact of adeno- and adenosquamous histology in the randomized trials of primary cisplatin-based chemoradiation for locally advanced cervical cancer. Methods Patients with adeno- and adenosquamous cervical carcinomas were retrospectively studied and compared to squamous cell carcinomas in GOG trials of chemoradiation. Results Among 1671 enrolled in clinical trials of chemoradiation, 182 adeno- and adenosquamous carcinomas were identified (10.9%). A higher percentage of adeno- and adenosquamous carcinomas were stage IB2 (27.5% versus 20.0%) and fewer had stage IIIB (21.4% versus 28.6%). The mean tumor size was larger for squamous than adeno- and adenosquamous. Adeno- and adenosquamous carcinomas were more often poorly differentiated (46.2% versus 26.8%). When treated with radiation therapy alone, the 70 patients with adeno- and adenosquamous carcinoma of the cervix showed a statistically poorer overall survival (p=0.0499) compared to the 647 patients with squamous cell carcinoma of the cervix. However, when treated with radiation therapy with concurrent cisplatin-based chemotherapy, the 112 patients with adeno- and adenosquamous carcinomas had a similar overall survival (p=0.459) compared the 842 patients with squamous cell carcinoma. Adverse effects to treatment were similar across histologies. Conclusion Adeno- and adenosquamous carcinomas of the cervix are associated with worse overall survival when treated with radiation alone but with similar progression-free and overall survival compared to squamous cell carcinomas of the cervix when treated with cisplatin based chemoradiation. PMID:25152438

  3. Concomitant chemobrachyradiotherapy with ifosfamide and cisplatin followed by consolidation chemotherapy in the treatment of locally advanced adenocarcinoma or adenosquamous carcinoma of the cervix uteri.

    PubMed

    Vrdoljak, E; Boraska Jelavic, T; Saratlija-Novakovic, Z; Hamm, W

    2005-01-01

    The optimal treatment of women with locally advanced adenocarcinoma or adenosquamous carcinoma of the cervix uteri is still undefined. We report a series of four consecutive patients with locally advanced adeno- or adenosquamous carcinomas of the uterine cervix (FIGO Stages IB-IIIB) treated by concomitant chemobrachyradiotherapy with ifosfamide and cisplatin followed by one to four cycles of consolidation chemotherapy with the same drug combination. After completion of this treatment all patients showed complete clinical remission. Now, after a median follow-up of 40 (range: 13.5-61) months all patients still present with no evidence of disease. Despite the low number of patients in this series we may conclude that concomitant chemobrachyradiotherapy with ifosfamide and cisplatin followed by consolidation chemotherapy with the same drug combination is an efficacious treatment of patients with locally advanced adeno- or adenosquamous carcinomas of the cervix uteri.

  4. Vascular endothelial growth factor (VEGF) expression is a prognostic factor for radiotherapy outcome in advanced carcinoma of the cervix

    PubMed Central

    Loncaster, J A; Cooper, R A; Logue, J P; Davidson, S E; Hunter, R D; West, C M L

    2000-01-01

    The aim of the study was to evaluate VEGF expression in tumour biopsies as a prognostic factor for radiotherapy outcome in advanced carcinoma of the cervix. A retrospective study was carried out on 100 patients. Pre-treatment tumour VEGF expression was examined immunohistochemically in formalin-fixed, paraffin-embedded biopsies using a widely available commercial antibody. A semi-quantitative analysis was made using a scoring system of 0, 1, 2, and 3, for increasing intensity of staining. High VEGF expression was associated with a poor prognosis. A univariate log rank analysis found a significant relationship with overall survival (P = 0.0008) and metastasis-free survival (P = 0.0062), but not local control (P = 0.23). There was no correlation between VEGF expression and disease stage, tumour differentiation, patient age, or tumour radiosensitivity (SF2). In a Cox multivariate analysis of survival VEGF expression was the most significant independent prognostic factor (P = 0.001). After allowing for VEGF only SF2 was a significant prognostic factor (P = 0.003). In conclusion, immunohistochemical analysis of VEGF expression is a highly significant and independent prognostic indicator of overall and metastasis-free survival for patients treated with radiotherapy for advanced carcinoma of the cervix. It is also a rapid and easy method that could be used in the clinical setting, to identify patients at high risk of failure with conventional radiotherapy who may benefit from novel approaches or chemoradiotherapy. © 2000 Cancer Research Campaign PMID:10944602

  5. Low podoplanin expression in pretreatment biopsy material predicts poor prognosis in advanced-stage squamous cell carcinoma of the uterine cervix treated by primary radiation.

    PubMed

    Dumoff, Kimberly L; Chu, Christina S; Harris, Eleanor E; Holtz, David; Xu, Xiaowei; Zhang, Paul J; Acs, Geza

    2006-05-01

    Lymphatic invasion and nodal metastasis are predictors of poor outcome in cervix carcinoma. We have recently found that low podoplanin immunoreactivity in cervix carcinoma correlated with the presence of lymphatic invasion and nodal metastasis. In the current study, we examined whether podoplanin expression in pretreatment cervical biopsies can predict the presence lymphatic invasion, nodal metastasis, and outcome in advanced-stage tumors treated by nonsurgical means. Podoplanin expression was analyzed by immunohistochemistry in 48 cervical biopsies and corresponding hysterectomy specimens of early-stage invasive squamous cell carcinoma and in 74 pretreatment biopsies from advanced-stage tumors treated with primary radiation. We found a highly significant correlation between podoplanin expression obtained in biopsy and corresponding hysterectomy materials (r = 0.8962, P < 0.0001). Low podoplanin expression showed a significant correlation with lymphatic invasion (P < 0.0001) and nodal metastasis (P = 0.0058). Low podoplanin expression in pretreatment biopsy material showed a significant correlation with poor disease-free (P = 0.0009) and overall (P = 0.0002) survival in advanced-stage tumors. Our results suggest that in advanced-stage cervix carcinomas treated by radiation, when traditional prognostic indicators are not available and treatment decisions are based on biopsy material and clinical staging parameters, examination of podoplanin expression in pretreatment biopsy material may be a useful marker to predict lymphatic metastasis and patient outcome. Prospective studies involving larger numbers of patients are needed to further evaluate the clinical utility of examination of podoplanin expression in patients with cervix carcinoma.

  6. HPV Genotypes Predict Survival Benefits From Concurrent Chemotherapy and Radiation Therapy in Advanced Squamous Cell Carcinoma of the Cervix

    SciTech Connect

    Wang, Chun-Chieh; Lai, Chyong-Huey; Huang, Yi-Ting; Chao, Angel; Chou, Hung-Hsueh; Hong, Ji-Hong

    2012-11-15

    Purpose: To study the prognostic value of human papillomavirus (HPV) genotypes in patients with advanced cervical cancer treated with radiation therapy (RT) alone or concurrent chemoradiation therapy (CCRT). Methods and Materials: Between August 1993 and May 2000, 327 patients with advanced squamous cell carcinoma of the cervix (International Federation of Gynecology and Obstetrics stage III/IVA or stage IIB with positive lymph nodes) were eligible for this study. HPV genotypes were determined using the Easychip Registered-Sign HPV genechip. Outcomes were analyzed using Kaplan-Meier survival analysis and the Cox proportional hazards model. Results: We detected 22 HPV genotypes in 323 (98.8%) patients. The leading 4 types were HPV16, 58, 18, and 33. The 5-year overall and disease-specific survival estimates for the entire cohort were 41.9% and 51.4%, respectively. CCRT improved the 5-year disease-specific survival by an absolute 9.8%, but this was not statistically significant (P=.089). There was a significant improvement in disease-specific survival in the CCRT group for HPV18-positive (60.9% vs 30.4%, P=.019) and HPV58-positive (69.3% vs 48.9%, P=.026) patients compared with the RT alone group. In contrast, the differences in survival with CCRT compared with RT alone in the HPV16-positive and HPV-33 positive subgroups were not statistically significant (P=.86 and P=.53, respectively). An improved disease-specific survival was observed for CCRT treated patients infected with both HPV16 and HPV18, but these differenced also were not statistically significant. Conclusions: The HPV genotype may be a useful predictive factor for the effect of CCRT in patients with advanced squamous cell carcinoma of the cervix. Verifying these results in prospective trials could have an impact on tailoring future treatment based on HPV genotype.

  7. The role of surgery in locally advanced carcinoma of cervix after sub-optimal chemoradiation: Indian scenario

    PubMed Central

    Kundargi, Rajshekar S.; Guruprasad, B.; Hanumantappa, Nikesh; Rathod, Praveen Shankar; Devi, Uma K.; Bafna, U. D.

    2013-01-01

    Background: Standard treatment of advanced cervical cancer is concurrent chemoradiation. Radical radiotherapy for carcinoma cervix includes pelvic external beam radiotherapy (EBRT) with the concomitant platinum based chemotherapy followed by intracavitary brachytherapy (ICBT) to boost central disease. Management of patients who are suboptimally treated, especially, after unsuccessful ICBT insertion is not well-defined. This study explores the role of hysterectomy in these patients. Materials and Methods: From January 2006 to December 2011, 38 patients with locally advanced cervical cancer, in whom ICBT insertion was unsuccessful, were analyzed retrospectively. Operable patients with no parametrial involvement underwent hysterectomy and outcomes (recurrence free and overall survival) were noted. Results: The major complications in post operative period were wound infection, paralytic ileus and bladder atony all of which were conservatively managed with no mortality. At median follow-up of 36 months (range 12-60 months) there was no recurrence in patients with stage 1B2 and stage IIA, 25 out of 38 (65.8%) were event free and the overall survival was 71%. Conclusion: Many patients in Indian scenario receive suboptimal therapy in locally advanced cervical cancer. EBRT with chemotherapy followed by type 1 extra-fascial hysterectomy can be a good alternative for these patients. PMID:24455590

  8. [Locally advanced carcinoma of the cervix uteri (stage IIB-IIIB TNM-UICC): radiotherapy combined with simultaneous daily low-dose platinum. Phase II study].

    PubMed

    Micheletti, E; La Face, B; Bianchi, E; Cagna, E; Sartori, E

    1996-05-01

    A prospective, single arm, phase-II trial was performed to assess the efficacy and local toxicity of the combination of low doses of platin and pelvic radiotherapy in patients with locally advanced carcinoma of the cervix. January, 1993, through August, 1994, twenty-three previously untreated patients with squamous carcinoma (stages IIB-IIIB UICC) entered the study. All patients were examined by a gynecologist and by a radiation oncologist and then submitted to conventional pretreatment staging procedures. Nine patients were classified as stage IIB and 14 patients as stage IIIB. Radiotherapy consisted of 60 Gy external beam irradiation (46 Gy to pelvis + 14 Gy boost to cervix uteri and parametria) plus one low dose rate intracavitary treatment to a dose of 8 Gy to point A. Cisplatin (3 mg/m2/day) or carboplatin (12 mg/m2/day) was also given for 6 weeks starting on radiotherapy day 1. The treatment was well tolerated and no patient required radiotherapy discontinuation. With a median follow-up time of 20 months, complete response was seen in 74% (17/23) of the patients. One of the 17 patients who achieved a complete remission, during follow-up, relapsed in the pelvis and one developed lung metastases. Total failure rate in the pelvis was 30.5% (7/23). Distant metastases were observed in 17.5% (4/23) of the patients. Actuarial overall and disease-free survival rates at 33 months were 69.1% and 65.2%, respectively. Late gastrointestinal toxicity (grade 3) occurred in 8.6% (2/23) of patients, with one patient developing a rectal ulcer-which was submitted to colostomy- and one patient a vaginal necrosis. The combination of platin and radiotherapy appears to be an effective regimen for the patients with locally advanced carcinoma of the cervix and caused a relatively low rate of late gastrointestinal complications.

  9. Carcinoma of the cervix with massive eosinophilia.

    PubMed

    Lowe, D G

    1988-04-01

    Massive local eosinophilia of 100 or more eosinophils per high power field was found in 3.2% cases of invasive carcinoma of the cervix. The prevalence, length of history before presentation to surgery and histological features were similar in patients from Great Britain and Malawi, but in both populations the mean age at diagnosis was lower than in patients with cervical carcinomas without tissue eosinophilia. In some of the tumours, the malignant cells were very difficult to find because of the eosinophil infiltrate, and misinterpretation as an inflammatory lesion was possible. In the absence of circulating eosinophilia, cervical carcinomas with massive eosinophilia were found to have a better prognosis than tumours without. Five patients had circulating eosinophilia as well as local tumour eosinophil infiltration, and each of them had extensive tumour spread.

  10. Cell Based Autologous Immune Enhancement Therapy (AIET) after Radiotherapy in a Locally Advanced Carcinoma of the Cervix

    PubMed Central

    Premkumar, Sumana; Dedeepiya, Vidyasagar Devaprasad; Terunuma, Hiroshi; Senthilkumar, Rajappa; Srinivasan, Thangavelu; Reena, Helen C.; Preethy, Senthilkumar; Abraham, Samuel J. K.

    2013-01-01

    Radiotherapy is the primary form of treatment in patients with locally advanced cervical carcinoma. However for residual disease in the form of the persistent lymph nodes, surgery or chemotherapy is recommended. As surgery is not acceptable by every patient and chemotherapy has associated side effects, we hereby report the positive outcome of in vitro expanded natural killer cell and activated T lymphocyte based autologous immune enhancement therapy (AIET) for the residual lymphadenopathy in a patient with locally advanced cervical cancer after radiation. After six transfusions of AIET, there was complete resolution of residual lymph nodes and there was no evidence of local lesion. The patient also reported improvement in quality of life. As AIET has been reported as the least toxic among the available therapies for cancer, combining AIET with conventional forms of therapy in similar patients might not only improve the outcome but may also help the patients achieve a good quality of life. PMID:23653878

  11. Small cell carcinoma of the cervix: a case report.

    PubMed

    Korcum, Aylin Fidan; Aksu, Gamze; Bozcuk, Hakan; Pestereli, Elif; Simsek, Tayup

    2008-04-01

    Small cell carcinoma of the uterine cervix accounts for 1-3% of all cervix cancers. It is an aggressive disease with a poor prognosis. To date, no effective treatment protocol has been determined. Surgery, radiotherapy, and chemotherapy have been used either alone or in combination. Recent data suggests that survival in patients with early staged small cell carcinoma of the cervix is better with surgery combined with chemo-radiotherapy. Here, we presented two patients with stage IB1 small cell carcinoma of the uterine cervix. For both patients, definitive surgery was performed with pelvic and para-aortic lymphadenectomy. Subsequently, they were treated with pelvic external radiotherapy and high-dose-rate intracavitary brachytherapy with concurrent cisplatin based chemotherapy. They were alive with no evidence of disease at 91 and 65 months, respectively.

  12. Carcinoma of the cervix: an epidemiologic study.

    PubMed

    Terris, M; Oalmann, M C

    1960-12-01

    122 patients with histologically confirmed squamous cell carcinoma of the cervix admitted to the gynecological wards of Charity Hospital in New Orleans from July 1, 1959, through March 31, 1960, were studied; suitable controls were selected from the same wards. All interviews were conducted by the same interviewer nurse who was unaware of the diagnoses. Hospital charts were later examined. Educational level of patients, occupation of husband and father, residence, original diagnosis, and religion were similar to those of controls. Less than 1/3 had more than grammar school education. Most husbands and fathers were farmers of unskilled laborers. In only 1/5 of the patients had the original cancer diagnosis been made by private physicians or at noncharity hospitals. About 45% were Catholics, 45% Baptists, and the remaining 10% other Protestant denominations. 49% of the patients and 43% of the controls reported 6 or more pregnancies. Douching practices were similar to controls; few had ever used other contraceptive measures. 13 patients and 6 controls had positive serological tests for syphilis. Only 6, 1 patient and 5 controls, had never been married. Of cancer patients, 47% had been married more than once vs. 16% of controls. 34% of the patients with cancer were married before the age of 17 vs. 14% of controls. 54% of patients with cancer and 26% of controls reported extramarital partners. 53% of patients had 1st coitus before age 17 vs. 26% of the controls. There was a considerably higher frequency of coitus in patients than in controls. It is concluded that no relation between number of pregnancies and cancer was shown. Douching with coal tar derivatives was not a factor. The association of carcinoma and syphilis was not certain as many had never had a serological test. The effect of circumcision of partners was not determined as it was often unknown. A significant association was shown with early marriage, extramarital relations, coitus at an early age, and

  13. Downregulation of Six MicroRNAs Is Associated with Advanced Stage, Lymph Node Metastasis and Poor Prognosis in Small Cell Carcinoma of the Cervix

    PubMed Central

    Huang, Long; Lin, Jia-Xin; Yu, Yan-Hong; Zhang, Mei-Yin; Wang, Hui-Yun; Zheng, Min

    2012-01-01

    Background Small cell carcinoma of the cervix (SCCC) is very rare, and due to the long time period required to recruit sufficient numbers of patients, there is a paucity of information regarding the prognostic factors associated with survival. MicroRNAs (miRNAs) have been used as cancer-related biomarkers in a variety of tumor types, and the objective of this study was to determine whether microRNA expression profiles can predict clinical outcome in SCCC. Methodology/Principal Findings Forty-four patients with SCCC who underwent radical hysterectomy between January 2000 and October 2009 were enrolled. Using the GeneCopoeia All-in-One™ Customized Human qPCR Primer Array, the expression profiles of 30 miRNAs associated with tumor metastasis was obtained from the formalin-fixed paraffin embedded samples of all 44 patients. Seven miRNAs, has-let-7c, has-miR-10b, has-miR-100, has-miR-125b, has-miR-143, has-miR-145 and has-miR-199a-5p were significantly down-regulated in advanced stage SCCCpatients (FIGO IB2-IV) compared to early stage SCCC patients (FIGOIB1). Among, downregulation of six miRNAs, has-let-7c, has-miR-100, has-miR-125b, has-miR-143, has-miR-145 and has-miR-199a-5p were significantly associated with lymph node metastasis and reduced survival in SCCC. Kaplan–Meier survival analyses revealed that SCCC patients with low expression of has-miR-100 (P = 0.019) and has-miR-125b (P = 0.020) projected a significant tendency towards poorer prognosis. Conclusions/Significance This study demonstrates that downregulation of 7 miRNA associated with advanced stage, 6 miRNAs with metastasis and 2 with poor prognosis in SCCC. Functional analysis of these miRNAs may enhance our understanding of SCCC, as altered expression of specific miRNAs may regulate the metastatic pathway and provide novel targets for therapy. PMID:22438992

  14. The American Brachytherapy Society Treatment Recommendations for Locally Advanced Carcinoma of the Cervix Part II: High Dose-Rate Brachytherapy

    PubMed Central

    Viswanathan, Akila N.; Beriwal, Sushil; De Los Santos, Jennifer; Demanes, D. Jeffrey; Gaffney, David; Hansen, Jorgen; Jones, Ellen; Kirisits, Christian; Thomadsen, Bruce; Erickson, Beth

    2012-01-01

    Purpose This report presents the 2011 update to the American Brachytherapy Society (ABS) high-dose-rate (HDR) brachytherapy guidelines for locally advanced cervical cancer. Methods Members of the American Brachytherapy Society (ABS) with expertise in cervical cancer brachytherapy formulated updated guidelines for HDR brachytherapy using tandem and ring, ovoids, cylinder or interstitial applicators for locally advanced cervical cancer were revised based on medical evidence in the literature and input of clinical experts in gynecologic brachytherapy. Results The Cervical Cancer Committee for Guideline Development affirms the essential curative role of tandem-based brachytherapy in the management of locally advanced cervical cancer. Proper applicator selection, insertion, and imaging are fundamental aspects of the procedure. Three-dimensional imaging with magnetic resonance or computed tomography or radiographic imaging may be used for treatment planning. Dosimetry must be performed after each insertion prior to treatment delivery. Applicator placement, dose specification and dose fractionation must be documented, quality assurance measures must be performed, and follow-up information must be obtained. A variety of dose/fractionation schedules and methods for integrating brachytherapy with external-beam radiation exist. The recommended tumor dose in 2 Gray (Gy) per fraction radiobiologic equivalence (EQD2) is 80–90 Gy, depending on tumor size at the time of brachytherapy. Dose limits for normal tissues are discussed. Conclusion These guidelines update those of 2000 and provide a comprehensive description of HDR cervical cancer brachytherapy in 2011. PMID:22265437

  15. Early Clinical Outcomes and Toxicity of Intensity Modulated Versus Conventional Pelvic Radiation Therapy for Locally Advanced Cervix Carcinoma: A Prospective Randomized Study

    SciTech Connect

    Gandhi, Ajeet Kumar; Sharma, Daya Nand; Rath, Goura Kisor; Julka, Pramod Kumar; Subramani, Vellaiyan; Sharma, Seema; Manigandan, Durai; Laviraj, M.A.; Kumar, Sunesh; Thulkar, Sanjay

    2013-11-01

    Purpose: To evaluate the toxicity and clinical outcome in patients with locally advanced cervical cancer (LACC) treated with whole pelvic conventional radiation therapy (WP-CRT) versus intensity modulated radiation therapy (WP-IMRT). Methods and Materials: Between January 2010 and January 2012, 44 patients with International Federation of Gynecology and Obstetrics (FIGO 2009) stage IIB-IIIB squamous cell carcinoma of the cervix were randomized to receive 50.4 Gy in 28 fractions delivered via either WP-CRT or WP-IMRT with concurrent weekly cisplatin 40 mg/m{sup 2}. Acute toxicity was graded according to the Common Terminology Criteria for Adverse Events, version 3.0, and late toxicity was graded according to the Radiation Therapy Oncology Group system. The primary and secondary endpoints were acute gastrointestinal toxicity and disease-free survival, respectively. Results: Of 44 patients, 22 patients received WP-CRT and 22 received WP-IMRT. In the WP-CRT arm, 13 patients had stage IIB disease and 9 had stage IIIB disease; in the IMRT arm, 12 patients had stage IIB disease and 10 had stage IIIB disease. The median follow-up time in the WP-CRT arm was 21.7 months (range, 10.7-37.4 months), and in the WP-IMRT arm it was 21.6 months (range, 7.7-34.4 months). At 27 months, disease-free survival was 79.4% in the WP-CRT group versus 60% in the WP-IMRT group (P=.651), and overall survival was 76% in the WP-CRT group versus 85.7% in the WP-IMRT group (P=.645). Patients in the WP-IMRT arm experienced significantly fewer grade ≥2 acute gastrointestinal toxicities (31.8% vs 63.6%, P=.034) and grade ≥3 gastrointestinal toxicities (4.5% vs 27.3%, P=.047) than did patients receiving WP-CRT and had less chronic gastrointestinal toxicity (13.6% vs 50%, P=.011). Conclusion: WP-IMRT is associated with significantly less toxicity compared with WP-CRT and has a comparable clinical outcome. Further studies with larger sample sizes and longer follow-up times are warranted to justify

  16. Pregnancy after radiation therapy for carcinoma of the cervix.

    PubMed

    Browde, S; Friedman, M; Nissenbaum, M

    1986-01-01

    A successful pregnancy after intracavitary radiation therapy for carcinoma of the cervix is described. An additional 13 similar cases from the literature are reviewed. The possible reasons for the occurrence of these pregnancies despite irradiation to the ovaries, cervical canal and endometrium are discussed. The fact is emphasized that no genetic damage to the child was expected.

  17. Proteomic analysis reveals tanshinone IIA enhances apoptosis of advanced cervix carcinoma CaSki cells through mitochondria intrinsic and endoplasmic reticulum stress pathways.

    PubMed

    Pan, Tai-Long; Wang, Pei-Wen; Hung, Yu-Chiang; Huang, Chun-Hsun; Rau, Kun-Ming

    2013-12-01

    Cervix cancer is the second most common cancer among women worldwide, whereas paclitaxel, the first line chemotherapeutic drug used to treat cervical cancer, shows low chemosensitivity on the advanced cervical cancer cell line. Tanshinone IIA (Tan IIA) exhibited strong growth inhibitory effect on CaSki cells (IC50 = 5.51 μM) through promoting caspase cascades with concomitant upregulating the phosphorylation of p38 and JNK signaling. Comprehensive proteomics revealed the global protein changes and the network analysis implied that Tan IIA treatment would activate ER stress pathways that finally lead to apoptotic cell death. Moreover, ER stress inhibitor could alleviate Tan IIA caused cell growth inhibition and ameliorate C/EBP-homologous protein as well as apoptosis signal-regulating kinase 1 mediated cell death. The therapeutic interventions targeting the mitochondrial-related apoptosis and ER stress responses might be promising strategies to conquer paclitaxel resistance. PMID:24167031

  18. Paraneoplastic Dermatomyositis with Carcinoma Cervix: A Rare Clinical Association

    PubMed Central

    Kumar, Sumir; Mahajan, B. B.; Kaur, Sandeep; Singh, Amarbir

    2014-01-01

    Dermatomyositis is an uncommon inflammatory myopathy associated with cutaneous manifestations. It may also occur as paraneoplastic syndrome associated with various malignancies, most common of which being lung, breast, stomach, rectum, kidney, or testicular cancer. A postmenopausal woman presented to us with generalized itching along with skin rash and proximal muscle weakness of 2 years' duration. Examination revealed heliotrope rash and mechanic hands and muscle power 2/5 in proximal muscle groups of both upper and lower limbs. A clinical diagnosis of dermatomyositis was made which was supported by raised lactate dehydrogenase levels and skin biopsy findings. Past history was significant for vaginal discharge and bleeding per vagina. Further work-up revealed carcinoma cervix and she was referred to oncology department for further management. Temporal relationship and improvement of muscle weakness with treatment of underlying neoplasm supported its paraneoplastic nature. So, final diagnosis of keratinizing squamous cell carcinoma of cervix with paraneoplastic dermatomyositis was made. A nationwide cohort study of 1,012 patients with dermatomyositis in Taiwan revealed only 3 patients with cervical cancer. So this case is being reported for its rare association with carcinoma cervix and to highlight the need of detailed evaluation for underlying malignancies in patients with dermatomyositis. PMID:25587465

  19. Radiation treatment of carcinoma of the cervix

    SciTech Connect

    Thar, T.L.; Million, R.R.; Daly, J.W.

    1982-09-01

    To give the optimal treatment to each individual with cancer of the cervix, there must be very close cooperation and professional rapport between the radiation oncologist and gynecologic oncologist. Patients should be evaluated together with a review of the pertinent pathology and diagnostic roentgenograms in order to determine the optimal, individualized treatment plan for each patient. In the radiotherapeutic management of patients with cervical cancer, meticulous care must be taken in the treatment setups for external radiotherapy and the intracavitary radium applications. External fields should be carefully shaped to minimize the amount of normal tissue treated. Radium applications must be carefully reviewed with attention to and correction of minor deviations in the radium geometry, which could give rise to hot or cold spots in the radium dosage. With attention paid to the above factors, radiotherapy in the treatment of cervical cancer can be extremely rewarding. The majority of the patients treated will be cured and will be able to return to normal, functional lives. Most of the patients seen with cervical cancer do not have other major medical illnesses that will limit their lifespan, and as a result, 10-, 20-, and 30-yr survivals after treatment are being reported.

  20. Serum copper levels in different stages of carcinoma cervix uteri.

    PubMed

    Singh, M; Dwivedi, S; Singh, G; Bajpai, M

    1990-01-01

    Copper is a normal constituent of the diet and is present in all living matter. It is an important trace metal required for different metabolic processes. Detecting alterations in serum copper has an important role in the early detection and diagnosis of malignancy. Serum copper estimation was conducted on 95 women aged 32-60 using the P.P. Doxidase method. 62 women of varying age and parity had different stages of carcinoma cervix uteri and comprised the study group, while the control group was comprised of 33 non-pregnant women of different ages and parity. Approximately 40% of women in both groups were aged 41-45 years. In the control group, the mean serum copper level of reproductive age women was 118.3 ug% and 111.2 ug% among women of menopausal age. A linear progressive increase of serum copper levels was found in the study group with increasing stages of cervical malignancy. The mean values of stages I, II, III, and IV were 162.2 ug%, 190.64 ug%, 201.78 ug%, and 220.8 ug%, respectively.

  1. [Radio-chemotherapy of cervix carcinoma. I. Clinical part].

    PubMed

    Paeschke, K D

    1976-04-01

    A prospective study was performed for a new model concerning the potentiation of radiation with Podophyllum (Proresid) and the radioprotection with Acethylhomocystein-thiolactone (Reducdyn) in cases of the squamous cell carcinoma of the uterine cervix. The study was carried out on the basis of alternated data of birth. The total number of the randomization was 256, consisting of 173 stages II und 83 stages III. All patients were irradiated with 6000 mgeh Ra and 4500 R 60Co. In addition to the irradiation one group of 128 patients received an infusion of 1g Podophyllum/day after irradiation. Another group of 46 patients was treated prior to irradiation with 1g Acethyl-homocystein-thiolactone (AHCT) and with Podophyllum after exposure. The total dosage was between 30 and 50g Pod. and 30 and 50g AHCT. It could be shown that the survival rate after three years was increased up to 15%. An earlier study revealed a five-year-survival rate of 23%.

  2. Mucoepidermoid Carcinoma of Uterine Cervix: A Distinct Pathological and Clinical Entity

    PubMed Central

    Selcuk, Ilker; Ozdal, Bulent; Turker, Mengu; Usubutun, Alp; Gungor, Tayfun; Meydanli, Mehmet Mutlu

    2015-01-01

    Mucoepidermoid carcinoma of uterine cervix is a rare tumor that has some individual features. Defining risk factors after surgery shape the postoperative treatment modality on cervical cancer patients. Although there is not a well-known strategy for the postoperative follow-up of mucoepidermoid carcinoma, the aggressive behaviour of this tumor makes the gynecological oncologists choose liberal therapies on these patients. PMID:26064727

  3. Neoadjuvant chemotherapy to radiation and concurrent chemoradiation for locally advanced squamous cell carcinoma of the cervix: a review of the recent literature.

    PubMed

    Colombo, A; Landoni, F; Maneo, A; Zanetta, G; Nava, S; Tancini, G

    1998-01-01

    Radiotherapy is the standard treatment for locally advanced cervical cancer; nevertheless it fails to control disease progression within the irradiation fields in more than 40% of cases, particularly in patients with bulky tumor. Distant metastases are not infrequent in more advanced cases. Chemotherapy has been integrated with radiotherapy to improve local control and treat distant subclinical metastases. Schedules of combined treatment more frequently represented by neoadjuvant chemotherapy followed by radiation (NACT) and by concomitant chemotherapy and radiation (CT-RT). A review of the recent literature is presented. The role of NACT is controversial: high response rates are reported but doubtful advantages in terms of survival or local control have been shown. In randomized trials, hydroxyurea concomitant to radiation improves local control and survival, particularly in stage IIIB and IVA. Several randomized trials of concurrent chemoradiation with 5FU, cisplatin and mitomycin C are underway, but few have been published: no significative differences are reported in term of local control or survival. Acute toxicity is higher than in radiation alone, but usually manageable. For the analysis of late morbidity a longer follow-up is required. Large randomized trials of adequate radiotherapy versus concomitant chemoradiation are necessary to refine our understanding of the benefits of this integrated treatment.

  4. Novel agents and treatment techniques to enhance radiotherapeutic outcomes in carcinoma of the uterine cervix

    PubMed Central

    2016-01-01

    Background Survival of patients with locally advanced carcinoma cervix (LACC) using the current standard of concurrent chemo-radiotherapy (CCRT) has reached a plateau over the last two decades. Loco-regional failure in first two years of treatment completion and distant metastasis in the subsequent years has put the survival curves at a halt. Strategies of induction and adjuvant chemotherapy have yielded little as has any advancement in techniques of delivery of radiation therapy. This article aims at discussing the current existing literature as well as promising novel strategies to enhance radiotherapeutic outcomes in carcinoma of the uterine cervix. Methods The review of English literature included phase I-III trials evaluating either a novel agent, novel application/modifications of an existing treatment regimen or an innovative treatment technique. The studies have been divided in to subsections with summary of most important findings at the end of each section. Results Despite CCRT being the ‘gold standard’ treatment, several issues like optimum drug combination, schedule of drug delivery, combination with molecular targeted agents etc. remain undefined. Taxane, topoisomerase and gemcitabine based regimen needs to be further explored and compared with cisplatin based CCRT regimen. Several approaches like local delivery of cytotoxic agents, use of nano-medicine with CCRT are appearing on horizon with promises for the future. Therapies need to be designed based on the human papillomavirus titers of the patients and incorporation of radiosensitizers as an effective way of palliation with short course of radiotherapy may further enhance the radiotherapeutic outcomes. Conclusions The results of the studies with novel agents and treatment techniques appear promising. Further research in this arena including incorporation of cost-effectiveness analysis and quality of life issues in future trial designs are warranted. PMID:26904571

  5. A rare case of renal metastasis from squamous cell carcinoma of the cervix.

    PubMed

    Kulkarni, Maithili Mandar; Khandeparkar, Siddhi Gaurish Sinai; Joshi, Avinash R; Kothikar, Vishakha

    2016-01-01

    Cervical cancer is the most frequent type of cancer in women in many developing countries. Squamous cell carcinoma of the cervix spreads principally by lymphatics and less commonly through blood vessels. The most frequent sites for those who develop distant metastasis include lungs (21%), lumbar and thoracic spine (16%), and para-aortic lymph nodes (7%). Metastasis to the kidney is extremely rare with <10 previously reported cases. We report a case of renal metastasis from squamous cell carcinoma of the cervix detected in end-stage kidney due to hydronephrosis. PMID:27499599

  6. Long-Term Outcome and Prognostic Factors for Adenocarcinoma/Adenosquamous Carcinoma of Cervix After Definitive Radiotherapy

    SciTech Connect

    Huang, Yi-Ting; Wang, Chun-Chieh; Tsai, Chien-Sheng; Lai, Chyong-Huey; Chang, Ting-Chang; Chou, Hung-Hsueh; Hsueh, Swei; Chen, Chien-Kuang; Lee, Steve P.; Hong, Ji-Hong

    2011-06-01

    Purpose: To study the outcomes of patients with adenocarcinoma/adenosquamous carcinoma (AC/ASC) of the cervix primarily treated with radiotherapy (RT), identify the prognostic factors, and evaluate the efficacy of concurrent chemoradiotherapy (CCRT) or salvage surgery. Methods and Materials: A total of 148 patients with Stage I-IVA AC/ASC of cervix after full-course definitive RT were included. Of the 148 patients, 77% had advanced stage disease. Treatment failure was categorized as either distant or local failure. Local failure was further separated into persistent tumor or local relapse after complete remission. The effectiveness of CCRT with cisplatin and/or paclitaxel was examined, and the surgical salvage rate for local failure was reviewed. Results: The 5-year relapse-free survival rate was 68%, 38%, 49%, 30%, and 0% for those with Stage IB/IIA nonbulky, IB/IIA bulky, IIB, III, and IVA disease, respectively, and appeared inferior to that of those with squamous cell carcinoma of the cervix treated using the same RT protocol. Incomplete tumor regression after RT, a low hemoglobin level, and positive lymph node metastasis were independent poor prognostic factors for relapse-free survival. CCRT with weekly cisplatinum did not improve the outcome for our AC/ASC patients. Salvage surgery rescued 30% of patients with persistent disease. Conclusion: Patients with AC/ASC of the cervix primarily treated with RT had inferior outcomes compared to those with squamous cell carcinoma. Incomplete tumor regression after RT was the most important prognostic factor for local failure. Salvage surgery for patients with persistent tumor should be encouraged for selected patients. Our results did not demonstrate a benefit of CCRT with cisplatin for this disease.

  7. Papillary Squamotransitional Cell Carcinoma of the Uterine Cervix: A Case Report and Review of the Literature.

    PubMed

    Akbar, Shomaila Aamir M; Tunio, Mutahir A; Al-Dandan, Sadeq; Salamah, Kareema Mohammed Y; AlAsiri, Mushabbab

    2016-01-01

    Introduction. Papillary squamotransitional cell carcinoma (PSTCC) is an uncommon histopathological variant of squamous cell carcinoma (SCC) of the uterine cervix, which occurs in postmenopausal women. Presentation of Case. Herein, we describe a case of a 63-year-old woman who presented with 4-month history of postmenopausal vaginal bleeding. Vaginal examination revealed a fragile lesion of size 1 × 1 cm invading left posterior vaginal fornice and parametrium. Biopsy showed the presence of papillae containing fibrovascular cores lined by multilayered atypical epithelial cells resembling squamous and transitional cell epithelium, confirming the diagnosis of PSTCC of the uterine cervix. After staging work-up she was staged according to the International Federation of Gynecology and Obstetrics (FIGO) staging system 2009 as FIGO IIB, and she was started on extended field concurrent chemoradiation. Discussion. PSTCC of the uterine cervix is an extremely rare and aggressive entity. PSTCC is often characterized by the presence of papillary structures with prominent fibrovascular cores. PSTCC of the uterine cervix should be differentiated from transitional cell carcinoma, squamous papilloma, papillary adenocarcinoma, and cervical intraepithelial neoplasia with papillary features. Conclusion. PSTCC of the uterine cervix is a diagnostic challenge; further studies regarding the mechanism underlying the development of PSCC are warranted. PMID:27656303

  8. Papillary Squamotransitional Cell Carcinoma of the Uterine Cervix: A Case Report and Review of the Literature

    PubMed Central

    Salamah, Kareema Mohammed Y.; AlAsiri, Mushabbab

    2016-01-01

    Introduction. Papillary squamotransitional cell carcinoma (PSTCC) is an uncommon histopathological variant of squamous cell carcinoma (SCC) of the uterine cervix, which occurs in postmenopausal women. Presentation of Case. Herein, we describe a case of a 63-year-old woman who presented with 4-month history of postmenopausal vaginal bleeding. Vaginal examination revealed a fragile lesion of size 1 × 1 cm invading left posterior vaginal fornice and parametrium. Biopsy showed the presence of papillae containing fibrovascular cores lined by multilayered atypical epithelial cells resembling squamous and transitional cell epithelium, confirming the diagnosis of PSTCC of the uterine cervix. After staging work-up she was staged according to the International Federation of Gynecology and Obstetrics (FIGO) staging system 2009 as FIGO IIB, and she was started on extended field concurrent chemoradiation. Discussion. PSTCC of the uterine cervix is an extremely rare and aggressive entity. PSTCC is often characterized by the presence of papillary structures with prominent fibrovascular cores. PSTCC of the uterine cervix should be differentiated from transitional cell carcinoma, squamous papilloma, papillary adenocarcinoma, and cervical intraepithelial neoplasia with papillary features. Conclusion. PSTCC of the uterine cervix is a diagnostic challenge; further studies regarding the mechanism underlying the development of PSCC are warranted. PMID:27656303

  9. Papillary Squamotransitional Cell Carcinoma of the Uterine Cervix: A Case Report and Review of the Literature

    PubMed Central

    Salamah, Kareema Mohammed Y.; AlAsiri, Mushabbab

    2016-01-01

    Introduction. Papillary squamotransitional cell carcinoma (PSTCC) is an uncommon histopathological variant of squamous cell carcinoma (SCC) of the uterine cervix, which occurs in postmenopausal women. Presentation of Case. Herein, we describe a case of a 63-year-old woman who presented with 4-month history of postmenopausal vaginal bleeding. Vaginal examination revealed a fragile lesion of size 1 × 1 cm invading left posterior vaginal fornice and parametrium. Biopsy showed the presence of papillae containing fibrovascular cores lined by multilayered atypical epithelial cells resembling squamous and transitional cell epithelium, confirming the diagnosis of PSTCC of the uterine cervix. After staging work-up she was staged according to the International Federation of Gynecology and Obstetrics (FIGO) staging system 2009 as FIGO IIB, and she was started on extended field concurrent chemoradiation. Discussion. PSTCC of the uterine cervix is an extremely rare and aggressive entity. PSTCC is often characterized by the presence of papillary structures with prominent fibrovascular cores. PSTCC of the uterine cervix should be differentiated from transitional cell carcinoma, squamous papilloma, papillary adenocarcinoma, and cervical intraepithelial neoplasia with papillary features. Conclusion. PSTCC of the uterine cervix is a diagnostic challenge; further studies regarding the mechanism underlying the development of PSCC are warranted.

  10. Prognostic Utility of Squamous Cell Carcinoma Antigen in Carcinoma of the Cervix: Association With Pre- and Posttreatment FDG-PET

    SciTech Connect

    Olsen, Jeffrey R.; Dehdashti, Farrokh; Siegel, Barry A.; Zighelboim, Israel; Grigsby, Perry W.; Schwarz, Julie K.

    2011-11-01

    Purpose: Squamous cell carcinoma antigen (SCC Ag) is a serum biomarker for squamous cell carcinoma (SCC) of the cervix. We investigated the prognostic significance of SCC Ag levels before and at the completion of chemoradiotherapy and compared these levels with the results of pre- and posttreatment positron emission tomography/computed tomography (PET/CT) using [{sup 18}F]fluorodeoxyglucose (FDG). Methods and Materials: The records of 63 women who underwent definitive chemoradiotherapy for SCC of the cervix were reviewed. SCC Ag levels were obtained before and at the completion of radiotherapy. Patients were divided into two groups on the basis of their pretreatment SCC Ag level (>30 ng/mL vs. {<=}30 ng/mL). Pre- and posttreatment FDG-PET/CT characteristics and progression-free survival (PFS) were analyzed according to SCC Ag groups. Results: Median follow-up was 12 months. Women with SCC Ag >30 ng/mL at diagnosis had more advanced lymph node disease on pretreatment FDG-PET/CT than those with SCC Ag {<=}30 ng/mL (p = .002). Women whose SCC Ag normalized at the completion of chemoradiotherapy were more likely to have a complete metabolic response on their 3-month posttreatment FDG-PET/CT than those whose SCC Ag did not normalize (p = .006). The 2-year PFS was 73% for patients with a SCC Ag level {<=}30 ng/mL at diagnosis compared with 0% for those with a SCC Ag level >30 ng/mL at diagnosis (p < .0001). The 2-year PFS was 62% for patients whose SCC Ag normalized at the completion of chemoradiotherapy compared with 0% for those whose SCC Ag did not normalize (p = .0004). Conclusion: Elevated SCC Ag at diagnosis and failure of the SCC Ag to normalize at the completion of treatment are associated with incomplete metabolic response and decreased PFS.

  11. A seven year review of invasive carcinoma of the cervix treated at the Johns Hopkins Hospital.

    PubMed

    Inalsingh, C H; Chandrasekaran, M S; Julian, C; Hazra, T

    1976-10-01

    172 cases of invasive carcinoma of the cervix treated at the Johns Hopkins Hospital are reviewed. Failure rates are examined by stage, demonstrating a high percentage of local recurrences in patients with late stage disease treated by a traditional regime of radiotherapy. Reasons for these failures are explored and a proposal for a more individualized approach to therapy is made. PMID:978858

  12. Surgical excision of lung metastases from squamous carcinoma of the cervix. A report of 2 cases.

    PubMed

    de Moor, N G; Berry, A V; Nissenbaum, M M

    1983-01-01

    These 2 case reports serve to emphasize two important points concerning carcinoma of the cervix: (i) blood-borne metastases are now frequently encountered in this disease; and (ii) in selected cases surgical excision of a secondary deposit in the lung is the treatment of choice and may even result in cure.

  13. Counterpoint: test the value of hyperthermia in patients with carcinoma of the cervix being treated with concurrent chemotherapy and radiation.

    PubMed

    Prosnitz, L; Jones, E

    2002-01-01

    Major advances in the treatment of locally advanced cervical carcinoma were reported in 1999-2000 in five studies from the Gynecologic Oncology Group, Radiation Therapy Oncology Group and Southwestern Oncology Group. Collectively these trials reported a decrease in the risk of recurrence or death from cervical cancer ranging from 30-50% with the use of concurrent chemoradiation, as compared with radiation alone. On the basis of these trials the National Cancer Institute in 1999 issued a clinical alert concluding 'Strong consideration should be given to the incorporation of concurrent cisplatin-based chemotherapy with radiation therapy in women who require radiation therapy for treatment of cervical cancer.' Concurrently with these publications there appeared the publication in the Lancet in 2000 of the Dutch Deep Hyperthermia Group trial of radiotherapy alone versus combined radiation and hyperthermia for locally advanced pelvic tumors including carcinoma of the cervix. This multi-center phase III trial demonstrated an approximate doubling of the three year survival from 27 to 51% for the addition of hyperthermia to radiotherapy in patients with locally advanced cervical carcinoma. Additional trials to test the value of hyperthermia in patients with cervical carcinoma treated with concurrent chemotherapy and radiation are imperative and take precedence over a trial to investigate the value of chemotherapy in patients treated with hyperthermia and radiation.

  14. Literature review with PGI guidelines for delineation of clinical target volume for intact carcinoma cervix.

    PubMed

    Bansal, Anshuma; Patel, Firuza D; Rai, Bhavana; Gulia, Abhishek; Dhanireddy, Bhaswanth; Sharma, S C

    2013-01-01

    For definitive treatment of carcinoma cervix with conformal radiation techniques, accurate target delineation is vitally important, yet a consensus definition of clinical target volume (CTV) remains variable within the literature. The aim of the present article is to review the guidelines for CTV delineation published in the literature and to present the guidelines practiced at our institute. For this a literature pub med/medline search was performed from January 2000 to December 2012 and reviewed to identify published articles on guidelines for CTV primary and pelvic lymph node (LN) delineation for carcinoma cervix. Taking into consideration the traditional bony landmark based fields for treating cancer cervix, the knowledge of the patterns of disease spread and recurrence and the findings from imaging studies identifying typical anatomic distributions of areas at risk of harbouring subclinical disease, the differences in various guidelines have been analyzed and discussed. The CTV in cervical cancer consists of the CTV nodal and CTV primary. In all the published guidelines, CTV nodal consists of common iliac, external iliac, internal iliac, pre-sacral and obturator group of lymph nodes, and CTV primary consists of the gross tumor volume, uterine cervix, uterine corpus, parametrium, upper third of vagina and uterosacral ligaments. The various guidelines differ however, in the definition for these individual component structures. This is the first report to provide the complete set of guidelines for delineating both the CTV primary and CTV nodal in combination.

  15. Microinvasive carcinoma of the uterine cervix. Diagnostic and therapeutic dilemma.

    PubMed

    Bellino, R; Wierdis, T; Arisio, R; Re, A; Tessarolo, M; Leo, L; Lauricella, A; Lanza, A

    1994-01-01

    Squamous microcarcinomas of the uterine cervix represent a focus of controversy regarding a useful clinical definition. The confusion of terminology and numerous pathological definitions have led to a great variety of surgical treatments from the cone to the radical hysterectomy, with pelvic adenectomy. This report analyses retrospectively 133 cases of Stage IA cervical cancers which have been followed up for 10-240 months. The purpose of this work is to seek a uniform therapeutical approach to cervical microcarcinoma with the review of International Literature. PMID:7828609

  16. Glassy cell carcinoma of the cervix: a literature review.

    PubMed

    Zolciak-Siwinska, A; Jonska-Gmyrek, J

    2014-08-01

    Glassy cell carcinoma (GCC) is a histologically aggressive subtype of cervical cancer with rapid growth and early metastases. The prognosis for patients with GCC is poor. This article reviews the literature pertinent to the epidemiology, cytology, pathology, immunohistochemistry, treatment and prognosis of GCC. MEDLINE (PubMed) was searched for all articles or abstracts on patients diagnosed with GCC published (in English) since the original definition by Glucksmann and Cherry, Cancer 1956;9:971. Accurate diagnosis of GCC enables implementation of the correct treatment strategy. Early-stage GCC should be treated with hysterectomy and pelvic lymph node dissection, with adjuvant radiochemotherapy if at least one intermediate or high risk factor for cervical cancer is present. Advanced GCC should be treated with neoadjuvant radiochemotherapy or chemotherapy with the aim of making the disease operable. There is a need for retrospective evaluation of GCC treatment from several centres to explore knowledge about this rare entity. Future studies should explore the role of targeted therapies and the most efficient chemotherapy regimen for the management of GCC.

  17. Jack fruit lectin binding pattern in carcinoma of the uterine cervix.

    PubMed

    Remani, P; Joy, A; Vijayan, K K; Ravindran, A; Haseena Beevi, V M; Vasudevan, D M; Vijayakumar, T

    1990-01-01

    A lectin was isolated and purified from the seeds of Jack Fruit (Artocarpus integrifolia) using a column of immobilized N-acetyl D-Galactosamine. The Jack Fruit lectin (JFL) was conjugated to horse radish peroxidase (HRP). The purified conjugate was used to study the binding properties of tissues from carcinomas of the uterine cervix. The binding to cancer tissues was compared with that of normal controls. The carcinomatous cells showed varying degrees of binding towards JFL in contrast to normal controls which generally had uniform binding. The nature and intensity of binding of the lectin with the cancer tissues suggest that this lectin may be used as a diagnostic marker in carcinoma of uterine cervix.

  18. Pretreatment apoptosis in carcinoma of the cervix correlates with changes in tumour oxygenation during radiotherapy

    PubMed Central

    Sheridan, M T; West, C M L; Cooper, R A; Stratford, I J; Logue, J P; Davidson, S E; Hunter, R D

    2000-01-01

    A relationship between hypoxia and apoptosis has been identified in vitro and in experimental tumours. The aim of this study was to investigate the relationship between apoptosis, hypoxia and the change in oxygenation during radiotherapy in human squamous cell carcinoma of the cervix. Forty-two patients with locally advanced disease underwent pretreatment evaluation of tumour oxygenation using an Eppendorf computerized microneedle electrode. Twenty-two of these patients also had a second evaluation of tumour oxygenation after receiving 40–45 Gy external beam radiotherapy. Paraffin-embedded histological sections were obtained from random pretreatment biopsies for all 42 patients. Apoptotic index (AI) was quantified by morphology on TUNEL stained sections. No correlation was found between pretreatment measures of AI and either the median pO2(r = 0.12, P = 0.44) or percentage of values < 5 mmHg (r = –0.02, P = 0.89). A significant positive correlation was found between AI and the change in tumour oxygenation (ratio of pre:post-treatment % values < 5 mmHg) following radiotherapy (r = 0.61, P = 0.002). The lack of correlation between apoptosis and hypoxia may occur because the Eppendorf measures both acute and chronic hypoxia, and the relative ability of acute hypoxia to induce apoptosis is unknown. These results indicate that cell death via apoptosis may be a mechanism of tumour reoxygenation during radiotherapy. © 2000 Cancer Research Campaign PMID:10735502

  19. Comparison of Cytologic Characteristics between Adenoid Cystic Carcinoma and Adenoid Basal Carcinoma in the Uterine Cervix

    PubMed Central

    Jeong, Juhyeon; Ha, Seung Yeon; Cho, Hyun Yee; Chung, Dong Hae; An, Jungsuk

    2015-01-01

    Background: Adenoid cystic carcinoma (ACC) and adenoid basal carcinoma (ABC) are rare in the uterine cervix. ACC is more aggressive than ABC, thus accurate differential diagnosis is important. In this study, we identified cytologic features useful in distinguishing these two tumors for diagnosis. Methods: Three cases of ACC and five cases of ABC were selected for this study. Cervicovaginal smear slides were reviewed retrospectively, and the area, circumference, major axis, and minor axis of nuclei were measured using an image analyzer. Results: ACC displayed three-dimensional clusters with a small acini pattern. ABC displayed peripheral palisading without an acini pattern. The nuclei of ACC were more irregular and angulated than those of ABC, and the former showed a coarsely granular chromatin pattern. The nucleic area, circumference, major axis, and minor axis were 18.556±8.665 µm2, 23.320±11.412 µm, 5.664±1.537 µm, and 4.127±1.107 µm in ACC and 11.017±4.440 µm2, 15.920±5.664 µm, 4.612±1.025 µm, and 3.088±0.762 µm in the cases of ABC. All measured values showed statistically significant difference (p < .001). Conclusions: Although the nuclei of both of these tumor types were oval shaped, inferred from the ratio of minor axis to major axis (0.728 in ACC and 0.669 in ABC), the area of nuclei was approximately 1.7 times larger in ACC than in ABC. Distinguishing nucleic features, including area, morphology, and chromatin pattern, may be helpful in making a correct diagnosis. PMID:26278519

  20. Palmar fasciitis and polyarthritis associated with squamous cell carcinoma of the cervix.

    PubMed

    Kase, H.; Aoki, Y.; Sugaya, S.; Takakuwa, K.; Tanaka, K.

    2000-11-01

    Palmar fasciitis and polyarthritis (PFPA) is an uncommon syndrome characterized by progressive and extensive rheumatic disease. We present the first example of PFPA in association with squamous cell carcinoma of the uterine cervix and peritoneal carcinoma. A 54-year-old woman developed pain in both shoulders and flexion deformities of all fingers in both hands due to an increasing swelling of both palms. She underwent surgery and histologic examination of the removed uterus revealed squamous cell carcinoma, nonkeratinizing type with a small portion of undifferentiated carcinoma. Chemotherapy resulted in an excellent response, during which the arthritic symptoms improved gradually. PFPA can occur in a wide range of cancers and warrants extensive investigation for a malignant tumor.

  1. Unusual case of cavitary lung metastasis from squamous cell carcinoma of the uterine cervix.

    PubMed

    Raissouni, Soundouss; Ghizlane, Rais; Mouzount, Houda; Saoussane, Kharmoum; Khadija, Setti; Zouaidia, Fouad; Latib, Rachida; Mrabti, Hind; Errihani, Hassan

    2013-01-01

    Spontaneous excavation of primary lung cancer is common; however cavitation of metastatic lung lesions is rare and usually confused with benign lesions. In Moroccan context tuberculosis is the first suspected diagnosis of lung excavations. We report a rare case of cavitary lung metastasis of a uterine cervix cancer, treated initially as tuberculosis. A 40-year old non-smoking woman with a known history of squamous cell carcinoma of the uterine cervix since August 2005; presented on September 2008 with right chest pain without fever, hemoptysis or weight loss. CT scan showed a thin walled cavity. Empirical Antibiotic therapy was conducted 15 days with poor outcome. Then antibacillary treatment was started with no proof of mycobacterial infection. A month later, the patient presented with gynecological bleeding and a pneumothorax. Bronchoscopy with transbronchial biopsy of the cavitary mass was performed. Pathology demonstrated a metastatic squamous cell carcinoma. Pelvic examination and MRI showed a subsequent local cervix recurrence. Patient underwent 3 courses of systemic chemotherapy. She died on June 2009 due to progressive disease. Even cavitary lung metastases are rare and benign differential diagnosis are more common, clinician should be careful in neoplastic context and investigation should be done to eliminate a recurrence. PMID:23560120

  2. [Carcinoma of the cervix uteri--the morphological changes after preoperative radiotherapy].

    PubMed

    Veselinova, T; Ivanova, R; Gorchev, G; Tsvetkov, Ch

    1998-01-01

    A retrospective morphological research is made on 11 patients with squamous cell carcinoma of the cervix for a three-years period of time (1995-1997). Preoperative radiotherapy (intracavitary radiotherapy with Cs and/or external radiation) is carried out. A control group of 10 patients with cancer of uterine cervix without preoperative radiotherapy is also studied. All of the women undergo a wider hysterectomy by the method of Piver class IV. The radiation alterations in the tumor and the surrounding normal uterine tissues are also researched. A full regression of the tumor Ts size. There are demonstrative changes in the tumor and surrounding normal tissues, which are the prove the answer to the ionizing irradiation.

  3. Tumor Heterogeneity of FIGO Stage III Carcinoma of the Uterine Cervix

    SciTech Connect

    Kim, Yong Bae; Lee, Ik Jae; Kim, Song Yih; Kim, Jun Won; Yoon, Hong In; Kim, Sang Wun; Kim, Sunghoon; Kim, Young Tae; Suh, Chang Ok; Kim, Gwi Eon

    2009-12-01

    Purpose: The purpose of this study was to analyze tumor heterogeneity based on tumor extent and suggest reappraisal of the system of the International Federation of Gynecology and Obstetrics (FIGO) for Stage III carcinoma of the uterine cervix from a radiotherapeutic viewpoint. Methods and Materials: Between 1986 and 2004, 407 patients with FIGO Stage III (FIGO Stage IIIa in 19 and IIIb in 388) were treated with external beam radiotherapy (RT) and high-dose rate brachytherapy. All patients were reviewed with respect to tumor extent. Patterns of failure and survival parameters were analyzed by use of the chi{sup 2} test and Kaplan-Meier method. Results: The complete response rate was 79.6%, and the 5-year overall survival rates for Stage IIIa and Stage IIIb carcinoma of the cervix were 82.1% and 54.8%, respectively. To determine which parameters of tumor extent had an influence on prognosis for Stage IIIb patients, pelvic wall (PW) extension and hydronephrosis (HD) retained significance on multivariate analysis. Stage IIIb patients were divided into three subgroups according to PW extension and HD: low risk (unilateral PW extension without HD), intermediate risk (HD without PW extension or bilateral PW extension without HD), and high risk (unilateral or bilateral PW extension with HD). The high-risk group had a remarkably low complete response rate, high locoregional failure rate, and low 5-year survival rate compared with the intermediate- and low-risk groups. Conclusions: FIGO Stage III carcinoma of the cervix covers considerably heterogeneous subgroups according to tumor extent. Before initiation of treatment, we suggest that physicians determine a tailored treatment policy based on tumor heterogeneity for each Stage III patient.

  4. Radical hysterectomy and pelvic lymphadenectomy for stage IB carcinoma of the cervix: 21 years experience.

    PubMed

    Artman, L E; Hoskins, W J; Bibro, M C; Heller, P B; Weiser, E B; Barnhill, D R; Park, R C

    1987-09-01

    From September 1971 through December 1982, 153 patients with Stage IB carcinoma of the cervix underwent radical hysterectomy and pelvic lymphadenectomy at two of the teaching hospitals of the Uniformed Services University of the Health Sciences. Records were retrospectively analyzed and independent pathologic review was performed. All surgical procedures were performed by fellows or senior residents under the direct supervision of the gynecologic oncology staff of the Walter Reed Army Medical Center or the Naval Hospital, Bethesda, Maryland. In this series, IB carcinoma was defined as squamous carcinoma clinically confined to the cervix with invasion greater than 5 mm from the basement membrane or any adenocarcinoma confined to the cervix. The average age of the patients was 38.3 years. The histologic types were squamous in 72%, adenocarcinoma in 16%, and adenosquamous in 10.5%. The mean operating time was 5 hr and 40 min with an average blood loss of 1800 cc. There were two ureterovaginal and two vesicovaginal fistulae for an overall fistula rate of 2.6%. Actuarial survival for these 153 patients is 84%. This extends the previous series of R. C. Park, W. E. Patow, R. E. Rogers, and E. A. Zimmerman, Obstet. Gynecol. 41, 117-122 (1973) of 122 cases collected from 1961 to September 1971 to 275 cases. In comparing the two time periods, no significant differences were found in operative technique or complications, but there was a change in the incidence of adenocarcinoma and mixed cell types and a difference in survival. A relatively higher incidence of more aggressive tumors may indicate the need for different therapeutic approaches in the future. PMID:3653772

  5. Carcinoma of the cervix: surgical staging and radiotherapy with 32 MeV Betatron

    SciTech Connect

    Shah, K.; Olson, M.H.; Dillard, E.A.

    1982-09-01

    Fifty-six patients with squamous cell carcinoma of the cervix were staged by exploratory laparotomy. Twenty-eight of them received radiotherapy with 32 MeV Betatron and intracavitary radium. Twenty-one patients with Stage IB or IIA had a radical hysterectomy, five had post-operative pelvic irradiation, and two had primary exenteration. An overall 23.2% of patients had metastases in the paraaortic fields. Four patients with paraaortic node disease received extended field irradiation: 4500 rad in 5 weeks to paraaortic nodes. Two of them are alive and disease-free at 5.5 to 6.5 years.

  6. Quality assurance program in radiotherapy for carcinoma of the uterine cervix.

    PubMed

    Smaniotto, D; Mantello, G; Valentini, V

    1996-01-01

    Some uncertainties which impact on the quality of exclusive radiation therapy of carcinoma of the cervix and the operational procedures followed to lower treatment inaccuracies, are analyzed. In particular the following phase of radiation therapy are considered: prescription: indication for the dose and volume to be treated with external beam radiotherapy (ERT) or intracavitary brachytherapy (BRT) according to the different forms; planning: definition of procedures for ERT and BRT optimization; implementation: analysis of systems for checking reproducibility and treatment tolerance; follow-up: planning of clinico-instrumental controls of disease evolution and late toxicity.

  7. BIRC2 amplification in squamous cell carcinomas of the uterine cervix.

    PubMed

    Choschzick, M; Tabibzada, A M; Gieseking, F; Woelber, L; Jaenicke, F; Sauter, G; Simon, R

    2012-08-01

    Oncogene amplification is a key step in cell transformation towards malignancy. Chromosomal aberrations involving the long arm of chromosome 11, including amplifications at 11q13 and 11q22, have been previously reported in cervical cancer. While the role of the CCND1 gene as the driver gene for 11q13 amplification is well established in different tumor types, the significance of the 11q22 amplicon is less clear. The 11q22 amplicon corresponds to several putative target genes including the apoptose inhibitor BIRC2, recently detected as amplified in cervical cancer cell lines. To better understand the distribution and frequency of 11q amplification sites in uterine cervical carcinomas, we analyzed BIRC2 and CCND1 copy number changes using fluorescence in situ hybridization in a tissue microarray containing 238 cervical cancers. High-level amplification of BIRC2 was found in 12.9 % of tumors. Amplification of BIRC2 in cervical carcinomas was homogeneous as shown in corresponding whole tissue sections of amplified tumors at the tissue microarray. BIRC2 amplification was significantly more frequent than CCND1 amplification (2.1 %) in our cohort (p < 0.01), and amplification of both genes were independent from each other. BIRC2 amplification was associated with younger-patient age (p < 0.05) and squamous cell differentiation (p = 0.025) of cervix carcinomas. However, BIRC2 copy number changes were not related to tumor stage, grading and nodal status of cervical cancers. In conclusion, BIRC2 is amplified in a subset of squamous cell carcinoma of the uterine cervix. Further studies are necessary to evaluate possible prognostic effects of BIRC2 copy number gains in cervical carcinomas.

  8. Presurgical assessment and therapy of microinvasive carcinoma of the cervix.

    PubMed

    Orlandi, C; Costa, S; Terzano, P; Martinelli, G N; Comerci, G; Guerra, B; Martellini, L

    1995-11-01

    Retrievable pathological specimens and clinical data on 70 patients with microinvasive carcinoma diagnosed on surgical specimens from cone biopsy or hysterectomy (Stage IA) were reviewed and compared to pertinent findings in the literature with the intent of evaluating diagnostic criteria and defining pathological features that may influence the outcome by therapy. Emphasis was given to the preoperative assessment emphasizing that both an accurate colposcopic evaluation and a detailed pathological analysis may reliably point to a conservative therapeutic approach. Increasing depth of stromal invasion was associated with lesion width as well as with endocervical extension, as measured on colposcopy, microcolpohisteroscopy, and histology. Lymph-vascular space involvement was significantly related to depth of invasion. Two patients of 28 with dissected nodes had node metastases as well as lymph-vascular space involvement. Both developed a pelvic recurrence. One had a > 1- to < or = 3-mm invasion depth, the other a > 3- to < or = 5-mm lesion invasion. While advocating a conservative procedure for Stage IA1, we suggest discrimination with regard to Stage IA2 because we believe that lymph-vascular involvement should be meticulously evaluated. In fact, > 1- to < or = 3-mm lesions without lymph-vascular space involvement can be conservatively treated, while for any other lesion falling within the Stage IA2 category a modified radical histerectomy plus pelvic lymphadenectomy should be recommended.

  9. [Breast metastasis of a squamous cell carcinoma of the uterine cervix. A case report].

    PubMed

    Yordanov, Y; Dimitrova, P

    2015-01-01

    The breast is an extremely rare target organ for metastasis of extramammary neoplasms. The occurence varies between 1.7% to 6.6% in autopsies; between 1.2% and 2% in clinical cases; and around 2.7% in sputum series. In accordance with the primary tumor localization, it is more common to find metastases of lymphoma, melanoma, rhabdomyosarcoma, tumors of the lung and ovarian tumors. Breast metastasis of the uterine cervix is a very seldomly found. According to the published literature so far there have been around 30 documented cases with such pathology. This study presents the case of a 48-year-old female with a squamous cell carcinoma of the uterine cervix, which was histologically verified in 2010. Three years after the initial tumor diagnosis, radiotherapy and chemotherapy, the patient was found to have a cystic tumor formation in one of her breasts. The formation was painful to pressure. Quadrantectomy with an open bisopsy was performed to the patient. Histological and immunohistochemical diagnosis rejected primary squamous cell carcinoma of the breast. The differential diagnosis of metastatic lesions in the breast is problematic and requires careful clinical history, immunohistochemical study and multidisciplinary approach in the management. Mammary metastases are a bad predictor and they serve as an indicator of generalized dissemination of the primary tumor process.

  10. [The reproductive function in women with preinvasive and microinvasive carcinomas of the cervix uteri treated by conization].

    PubMed

    Chakalova, G; Karag'ozov, A; Diankova, Ts

    1990-01-01

    An inquiry was carried out on 46 women with preclinical carcinoma of the uterine cervix, treated with conization at the gynecological clinic of the National Oncological Center. Women were at the age of 22 to 38 years. Conization was made on 8 women on account of microinvasive carcinoma with invasion up to 1000 mkm, but on 38 women--on account of carcinoma of 0 degree. 26 women became pregnant after conization but 9 of them performed induced abortion and 2-therapeutic abortion. Pregnancy of 5 women ended with spontaneous abortion during the first trimester, one woman waited for delivery and 9 women delivered on term and without interventions. One woman delivered twice. The first trimester was risky for women with preclinical carcinoma of the uterine cervix, treated with conization.

  11. Low dynamin 2 expression is associated with tumor invasion and metastasis in invasive squamous cell carcinoma of cervix.

    PubMed

    Lee, Yoo-Young; Do, In-Gu; Park, Young Ae; Choi, Jung-Joo; Song, Sang Yong; Kim, Chul Jung; Kim, Min Kyu; Song, Tae Jong; Park, Hwang Shin; Choi, Chel Hun; Kim, Tae-Joong; Kim, Byoung-Gie; Lee, Jeong-Won; Bae, Duk-Soo

    2010-08-15

    Dynamin 2 is known as a protein involved in cell migration and endocytosis. We aimed to investigate the association between dynamin 2 expressions and tumor progression in early cervical carcinoma (IB1-IIA). Dynamin 2 expression was evaluated at protein level in thirty seven paraffin-embedded, formalin-fixed tissues including four normal cervix tissues and compared with pathologic risk factors for recurrence after surgery in thirty three patients with squamous cell carcinoma of the cervix. The expression of dynamin 2 was not different according to clinical stage and lympho-vascular space invasion. However, there were inverse correlations between dynamin 2 expression and the depth of invasion in cervix (p = 0.003) and lymph node (LN) metastasis (p = 0.001). To evaluate the mechanism of dynamin 2 in tumor invasion and metastasis, we performed an in vitro experiment with dynamin 2 siRNA using several cervical carcinoma cell lines such as HeLa, MS751 and SiHa cells. We found the inhibition of dynamin 2 using specific siRNA enhanced the expression of matrix metalloproteinase-2. These results suggested that dynamin 2 might be involved in preventing tumor invasion and LN metastasis, possibly in relation with extracellular matrix degradation, and may be a prognostic marker for these risk factors in early squamous cell carcinoma of the cervix.

  12. CDC27 protein is involved in radiation response in squamous cell cervix carcinoma.

    PubMed

    Rajkumar, T; Gopal, G; Selvaluxmi, G; Rajalekshmy, K R

    2005-10-01

    In the present study, an attempt was made to identify genes involved in radiation response in cervix carcinoma. Differential display technique was used to study the expression profiles of tumour biopsy samples obtained from patients, responding and not responding to treatment. The samples were obtained prior to radiotherapy and subsequent to treatment with Tele-radiation at 10 Gray (Gy). One of the differentially expressed cDNAs, when sequenced was identified to be CDC27. Immuno-histochemical analysis of pre- and post-treated tumour samples from fifteen patients showed the downregulation of expression of CDC27 protein in seven patients. Down-regulation was associated with poorer response to radiotherapy. Cervical cancer cell lines SiHa and C33A were irradiated and their nuclei were stained for expression of CDC27 and analyzed using fluorescent-activated cell sorting (FACS). Down-regulation of CDC27 protein in the irradiated SiHa cell line was associated with greater survival fraction, compared to the irradiated C33A cell line, which had only slight fall in the level of CDC27 protein. This is the first study to suggest a role for CDC27 in radiation response. However, a larger cohort is needed to further confirm the value of CDC27 protein as a predictive marker, for radiation response in cervix cancer.

  13. A pilot study on concurrent platinum chemotherapy and intracavitary brachytherapy for locally advanced cancer of the uterine cervix.

    PubMed

    Koumantakis, E; Haralambakis, Z; Koukourakis, M; Mazonakis, M; Haldeopoulos, D; Papageorgiou, N; Livas, V; Froudarakis, G; Varveris, H

    1998-05-01

    This study aims to evaluate the feasibility, toxicity and efficacy of concurrent chemotherapy with platinum compounds and brachytherapy, for locally advanced carcinoma of the cervix (Stages IIA/B, IIIA). The hypothesis was that synchronous chemo-brachytherapy may be sufficient to cause down-staging of the tumour, to render it operable, and hopefully improve the prognosis. 36 women with locally advanced cervical cancer were treated with concomitant brachytherapy and chemotherapy before surgery and/or definitive external radiotherapy. All patients received two caesium-137 Selectron MDR applications, 1 week apart. The dose calculated to point A for each implant was 20-25 Gy. Chemotherapy consisting of continuous cisplatin infusion (50 mg m2) and of carboplatin (300 mg m-2) was given simultaneously with intracavitary irradiation during the first and second application, respectively. The combined therapy was followed when feasible by radical hysterectomy, pelvic lymphadenectomy and pelvic radiotherapy. Patients deemed ineligible for surgery because of poor response were given full dose external radiotherapy. 31/36 patients were treated by Wertheim hysterectomy of whom 10 had negative lymph nodes and resection margins. Definitive external radiotherapy was given in the remaining five patients. Overall, 83% were disease free at 2.8 years mean follow-up. The most frequent acute side-effects of chemobrachytherapy were nausea and vomiting. No renal toxicity was observed. Thrombocytopenia was seen in five patients and was responsible for delayed surgery in four patients. Concerning late effects, two patients developed grade 2 intestinal sequelae, two mild frequency and two vaginal stenosis. One rectovaginal and one vesicovaginal fistula developed in two patients; and a third patient had a fistula associated with tumour recurrence. Concurrent brachytherapy and chemotherapy with platinum compounds is well tolerated and effective in reducing tumour bulk before definitive local

  14. Clinical results in carcinoma of the cervix: radium compared to caesium using remote afterloading.

    PubMed

    Jackson, S M; Fairey, R N; Kornelsen, R O; Young, M E; Wong, F L

    1989-05-01

    In 1979 the Cancer Control Agency of British Columbia changed from radium to remote controlled afterloaded caesium in the treatment of carcinoma of the cervix. In the 3 years prior to the change, 139 patients received radium as part of their treatment and in the 3 years after the change, 158 patients received caesium. Overall referral patterns, patient and cancer demographics, and treatment policies were stable throughout the 6-year period. Radiotherapy technique, dose, dose distribution and dose rate were comparable for both radium and caesium treated patients. The results of treatment in the two time periods showed no difference in survival, local tumour control or complications. The use of afterloading has not compromised treatment results and has allowed better nursing care for patients and protection from radiation for all staff. PMID:2752690

  15. Combined radiation and surgical treatment for carcinoma of the uterine cervix. [Efficacy and complications

    SciTech Connect

    Einhorn, N.; Bygdeman, M.; Sjoeberg, B.

    1980-02-15

    The simultaneous development of two techniques (radiotherapy and surgery) for the treatment of cervical carcinoma at the beginning of this century set off a controversy as to which of these approaches is to be preferred. From the fund of experience built up over the years, it is now evident that neither of these approaches is the more suitable one for all cervical carcinoma patients. Since the early sixties, women under 41 years of age with Stages I B and II A carcinoma of the cervix were routinely given a combination of irradiation and surgical treatment in our department. Because of preliminary observations of increased complication rate in these series, the method was dropped during 1970 to 1972 and radiotherapy was used mainly. As the incidence of local recurrence increased, the combined therapy was then again taken up in 1973. In the study reported here a comparison of the two methods was performed with respect to the recurrence-free survival and the incidence of complications.

  16. [Treatment of pelvic recurrences of carcinoma of the cervix uteri by radiotherapy alone].

    PubMed

    Bignardi, M; Bardelli, D; Bertoni, F; Tordiglione, M

    1988-05-01

    The best way to treat locally recurrent carcinoma of the uterine cervix has not been established. Our retrospective study refers to 37 consecutive patients, with recurrence in the pelvis, treated by radiotherapy alone. Thirty patients were treated by external beam therapy alone; intracavitary brachytherapy alone was adopted in 3 patients and a combination of both techniques in 4 patients. The total radiation dose exceeded 60 Gy in 62% of cases. A complete clinical response was observed in 54% of patients and a partial response in 32.4%. Overall crude survival was 70.3%, 28.9% and 23.2% at 1, 3 and 5 years respectively. In patients with recurrent tumors less than 40 mm in diameter a threefold 3-year survival was achieved (48.6% vs. 14.5%, p less than 0.025). With total doses higher than 60 Gy the 3-year survival resulted to be far better than with lower doses (39.1% vs. 10%, p less than 0.025). A significant advantage was also observed in the "complete responders" group (44% vs. 11.8%), but this difference can be explained by the link between response and the above-mentioned basic prognostic factors. Acute side effects and late complications were moderate and did not correlate with the type of primary treatment. A significant percentage (about 25%) of patients with locally recurrent cervix carcinoma may reach medium-term survival; better results can be achieved in selected groups with favourable prognostic factors and with adequate radiotherapeutic treatment.

  17. Serum alpha-N-acetylgalactosaminidase is associated with diagnosis/prognosis of patients with squamous cell carcinoma of the uterine cervix.

    PubMed

    Reddi, A L; Sankaranarayanan, K; Arulraj, H S; Devaraj, N; Devaraj, H

    2000-09-29

    Serum alpha-N-acetylgalactosaminidase (NaGalase) is responsible for the deglycosylation of vitamin D(3)-binding protein (Gc protein). The deglycosylated Gc protein cannot be converted into major macrophage-activating factor (MAF), leading to immunosuppression. NaGalase is universally detected in a variety of cancer patients, but not in healthy individuals (Cancer Res. 56 (1997) 2827-2831). However, the diagnostic/prognostic utility of NaGalase in squamous cell carcinoma (SCC) of the uterine cervix is not known. To address this issue, the serum NaGalase was quantitatively determined in 210 patients with different stages of SCC of the uterine cervix. NaGalase levels were increased with the progression of the cancer. After radiotherapy, the increased levels returned toward or to normal levels in early stages (FIGO stage I-IIB) but not in advanced stages (FIGO stage III-IV). The present study revealed that the amount of NaGalase in the patient's bloodstream reflects the tumor burden and aggressiveness of the disease. We conclude that NaGalase is an independent predictor of diagnosis/prognosis in SCC of the uterine cervix, and therefore suggest that quantitative NaGalase alteration may reflect important differences in the immunological functions of these neoplasms. PMID:10940510

  18. Dose verification in carcinoma of uterine cervix patients undergoing 3D conformal radiotherapy with Farmer type ion chamber

    PubMed Central

    Srinivas, Challapalli; Kumar, P Suman; Ravichandran, Ramamoorthy; Banerjee, S; Saxena, P.U; Kumar, E.S Arun; Pai, Dinesh K.

    2014-01-01

    External beam radiotherapy (EBRT) for carcinoma of uterine cervix is a basic line of treatment with three dimensional conformal radiotherapy (3DCRT) in large number of patients. There is need for an established method for verification dosimetry. We tried to document absorbed doses in a group of carcinoma cervix patients by inserting a 0.6 cc Farmer type ion chamber in the vaginal cavity. A special long perspex sleeve cap is designed to cover the chamber for using in the patient's body. Response of ionization chamber is checked earlier in water phantom with and without cap. Treatment planning was carried out with X-ray computed tomography (CT) scan and with the chamber along with cap in inserted position, and with the images Xio treatment planning system. Three measurements on 3 days at 5-6 fraction intervals were recorded in 12 patients. Electrometer measured charges are converted to absorbed dose at the chamber center, in vivo. Our results show good agreement with planned dose within 3% against prescribed dose. This study, is a refinement over our previous studies with transmission dosimetry and chemicals in ampules. This preliminary work shows promise that this can be followed as a routine dose check with special relevance to new protocols in the treatment of carcinoma cervix with EBRT. PMID:25525313

  19. Is cervical screening preventing adenocarcinoma and adenosquamous carcinoma of the cervix?

    PubMed Central

    Landy, Rebecca; Sasieni, Peter D.

    2016-01-01

    While the incidence of squamous carcinoma of the cervix has declined in countries with organised screening, adenocarcinoma has become more common. Cervical screening by cytology often fails to prevent adenocarcinoma. Using prospectively recorded cervical screening data in England and Wales, we conducted a population‐based case–control study to examine whether cervical screening leads to early diagnosis and down‐staging of adenocarcinoma. Conditional logistic regression modelling was carried out to provide odds ratios (ORs) and 95% confidence intervals (CIs) on 12,418 women with cervical cancer diagnosed between ages 30 and 69 and 24,453 age‐matched controls. Of women with adenocarcinoma of the cervix, 44.3% were up to date with screening and 14.6% were non‐attenders. The overall OR comparing women up to date with screening with non‐attenders was 0.46 (95% CI: 0.39–0.55) for adenocarcinoma. The odds were significantly decreased (OR: 0.22, 95% CI: 0.15–0.33) in up to date women with Stage 2 or worse adenocarcinoma, but not for women with Stage1A adenocarcinoma 0.71 (95% CI: 0.46–1.09). The odds of Stage 1A adenocarcinoma was double among lapsed attenders (OR: 2.35, 95% CI: 1.52–3.62) compared to non‐attenders. Relative to women with no negative cytology within 7 years of diagnosis, women with Stage1A adenocarcinoma were very unlikely to be detected within 3 years of a negative cytology test (OR: 0.08, 95% CI: 0.05–0.13); however, the odds doubled 3–5 years after a negative test (OR: 2.30, 95% CI: 1.67–3.18). ORs associated with up to date screening were smaller for squamous and adenosquamous cervical carcinoma. Although cytology screening is inefficient at preventing adenocarcinomas, invasive adenocarcinomas are detected earlier than they would be in the absence of screening, substantially preventing Stage 2 and worse adenocarcinomas. PMID:27096255

  20. Multivariate Analysis of Para-Aortic Lymph Node Recurrence After Definitive Radiotherapy for Stage IB-IVA Squamous Cell Carcinoma of Uterine Cervix

    SciTech Connect

    Huang, E.-Y.; Wang, C.-J.; Chen, H.-C.; Fang, F.-M.; Huang, Y.-J.; Wang, C.-Y.; Hsu, H.-C.

    2008-11-01

    Purpose: To evaluate the pretreatment risk factors of para-aortic lymph node (PALN) recurrence after primary radiotherapy for cervical cancer. Methods and Materials: Between May 1992 and January 2006, the data from 758 patients with squamous cell carcinoma of the uterine cervix were retrospectively analyzed. No patient had undergone PALN radiotherapy as their initial treatment. PALN recurrence was diagnosed by computed tomography. PALN relapse-free status was determined clinically or radiographically. We analyzed the actuarial rates of PALN recurrence using Kaplan-Meier curves. Multivariate analyses were performed with Cox regression models. Results: Of the 758 patients, 38 (5%) and 42 (6%) had isolated and nonisolated PALN recurrences after a median follow-up of 50 months (range, 2-159 months), respectively. The 3-year and 5-year overall survival rate after PALN recurrence was 35% and 28%, respectively. A squamous cell carcinoma antigen (SCC-Ag) level >40 ng/mL (p <0.001), advanced parametrial involvement (score 4-6; p = 0.002), and the presence of pelvic lymphadenopathy (p = 0.007) were independent factors associated with PALN relapse on multivariate analysis. The 5-year PALN recurrence rate in patients with a SCC-Ag level >40 ng/mL, SCC-Ag level of 20-40 ng/mL, parametrial score of 4-6, pelvic lymphadenopathy, and no risk factors was 57%, 22%, 34%, 37%, and 9%, respectively. Conclusions: Patients with squamous cell carcinoma of the uterine cervix and a high SCC-Ag level, pelvic lymphadenopathy, or advanced PM involvement were predisposed to PALN recurrence after definitive radiotherapy. More intensive follow-up schedules are suggested for early detection and salvage in high-risk patients.

  1. Patient-derived xenograft models of squamous cell carcinoma of the uterine cervix.

    PubMed

    Rofstad, Einar K; Simonsen, Trude G; Huang, Ruixia; Andersen, Lise Mari K; Galappathi, Kanthi; Ellingsen, Christine; Wegner, Catherine S; Hauge, Anette; Gaustad, Jon-Vidar

    2016-04-10

    Patient-derived xenograft (PDX) models of cancer are considered to reflect the biology and treatment response of human tumors to a larger extent than xenograft models initiated from established cell lines. The characterization of a panel of four novel PDX models of cervical carcinoma of the uterine cervix is described in this communication. The outcome of treatment differed substantially among the donor patients, and the PDX models were found to mirror the histology, aggressiveness, and metastatic propensity of the donor patients' tumors. Two of the models (BK-12 and LA-19) were highly metastatic, one model (ED-15) was poorly metastatic, and one model (HL-16) was non-metastatic. The primary tumors of the two highly metastatic models showed high density of intratumoral lymphatics, whereas the other two models did not develop intratumoral lymphatics. The potential of the models to metastasize to lymph nodes was associated with high expression of both angiogenesis-related genes and cancer stem cell-related genes. The models may be highly valuable for studying mechanisms linking lymph node metastasis to lymphangiogenesis, hemangiogenesis, and the presence of cancer stem cells. PMID:26828134

  2. Hydroxyurea: a radiation potentiator in carcinoma of the uterine cervix. A randomized double-blind study

    SciTech Connect

    Piver, M.S.; Barlow, J.J.; Vongtama, V.; Blumenson, L.

    1983-12-01

    From June, 1972, to December, 1976, 40 patients with FIGO (International Federation of Gynaecology and Obstetrics) Stage IIB carcinoma of the uterine cervix were entered into a prospective, double-blind, randomized study to evaluate the possible radiation-potentiating properties (i.e., improved survival) of the S-phase cell cycle-specific inhibitor of DNA synthesis, hydroxyurea. All patients were documented to be without aortic lymph node metastasis by pretherapy staging para-aortic lymphadenectomy. All 40 patients were followed up for longer than 5 years (5.2 to 9.2 years) or until death. The double-blind code was not broken until all patients had been followed up for a minimum of 2 to 5 years. Leukopenia (white blood cell count less than 2,500 mm3) was significantly increased in the patients given hydroxyurea as compared to those given placebo (P less than 0.0001). There was no statistically significant difference relative to anemia, thrombocytopenia, radiation-induced skin reaction, and radiation-induced intestinal reaction between the patients given placebo or those given hydroxyurea. Life-table survival for the patients given hydroxyurea was 94% as compared to 53% for the patients given placebo (P . 0.006). Only one (5%) patient given hydroxyurea died of cervical cancer. Of the other patients who died in the group given hydroxyurea, all were confirmed by postmortem examination to have been without recurrent cervical cancer. In contrast, 45% (nine) of the patients given placebo died of cervical cancer.

  3. Patient-derived xenograft models of squamous cell carcinoma of the uterine cervix.

    PubMed

    Rofstad, Einar K; Simonsen, Trude G; Huang, Ruixia; Andersen, Lise Mari K; Galappathi, Kanthi; Ellingsen, Christine; Wegner, Catherine S; Hauge, Anette; Gaustad, Jon-Vidar

    2016-04-10

    Patient-derived xenograft (PDX) models of cancer are considered to reflect the biology and treatment response of human tumors to a larger extent than xenograft models initiated from established cell lines. The characterization of a panel of four novel PDX models of cervical carcinoma of the uterine cervix is described in this communication. The outcome of treatment differed substantially among the donor patients, and the PDX models were found to mirror the histology, aggressiveness, and metastatic propensity of the donor patients' tumors. Two of the models (BK-12 and LA-19) were highly metastatic, one model (ED-15) was poorly metastatic, and one model (HL-16) was non-metastatic. The primary tumors of the two highly metastatic models showed high density of intratumoral lymphatics, whereas the other two models did not develop intratumoral lymphatics. The potential of the models to metastasize to lymph nodes was associated with high expression of both angiogenesis-related genes and cancer stem cell-related genes. The models may be highly valuable for studying mechanisms linking lymph node metastasis to lymphangiogenesis, hemangiogenesis, and the presence of cancer stem cells.

  4. Irradiation of para-aortic lymph node metastases from carcinoma of the cervix or endometrium

    SciTech Connect

    Komaki, R.; Mattingly, R.F.; Hoffman, R.G.; Barber, S.W.; Satre, R.; Greenberg, M.

    1983-04-01

    Twenty-two patients with biopsy-proved para-aortic lymph node metastases from carcinoma of the cervix (15 patients) or endometrium (7 patients) received a median dose of 5,000 rad/25 fractions. Para-aortic nodal metastases were controlled in 77% of cases. Control was significantly lower following radical retroperitoneal lymph node dissection than less extensive sampling procedures. Obstruction of the small bowel developed in 3 patients with tumor recurrence in the para-aortic region. Eight of the 10 patients who were disease-free at 2 years received >5,000 rad. Three patients were still alive without disease at 129, 63, and 60 months, respectively. The 5-year disease-free survival rate was 40% for cervical cancer and 60% for endometrial cancer: in the former group, it was significantly different depending on whether the para-aortic nodes were irradiated (40%) or not (0%). The authors suggest that 5,000-5,500 rad in 5-5.5 weeks is well tolerated and can control aortic nodal metastases in cervical and possibly endometrial cancer.

  5. Implementation of a High-Dose-Rate Brachytherapy Program for Carcinoma of the Cervix in Senegal: A Pragmatic Model for the Developing World

    SciTech Connect

    Einck, John P.; Hudson, Alana; Shulman, Adam C.; Yashar, Catheryn M.; Dieng, Mamadou M.; Diagne, Magatte; Gueye, Latifatou; Gningue, Fama; Gaye, Pape M.; Fisher, Brandon J.; Mundt, Arno J.; Brown, Derek W.

    2014-07-01

    West Africa has one of the highest incidence rates of carcinoma of the cervix in the world. The vast majority of women do not have access to screening or disease treatment, leading to presentation at advanced stages and to high mortality rates. Compounding this problem is the lack of radiation treatment facilities in Senegal and many other parts of the African continent. Senegal, a country of 13 million people, had a single {sup 60}Co teletherapy unit before our involvement and no brachytherapy capabilities. Radiating Hope, a nonprofit organization whose mission is to provide radiation therapy equipment to countries in the developing world, provided a high-dose-rate afterloading unit to the cancer center for curative cervical cancer treatment. Here we describe the implementation of high-dose-rate brachytherapy in Senegal requiring a nonstandard fractionation schedule and a novel treatment planning approach as a possible blueprint to providing this technology to other developing countries.

  6. Implementation of a high-dose-rate brachytherapy program for carcinoma of the cervix in Senegal: a pragmatic model for the developing world.

    PubMed

    Einck, John P; Hudson, Alana; Shulman, Adam C; Yashar, Catheryn M; Dieng, Mamadou M; Diagne, Magatte; Gueye, Latifatou; Gningue, Fama; Gaye, Pape M; Fisher, Brandon J; Mundt, Arno J; Brown, Derek W

    2014-07-01

    West Africa has one of the highest incidence rates of carcinoma of the cervix in the world. The vast majority of women do not have access to screening or disease treatment, leading to presentation at advanced stages and to high mortality rates. Compounding this problem is the lack of radiation treatment facilities in Senegal and many other parts of the African continent. Senegal, a country of 13 million people, had a single (60)Co teletherapy unit before our involvement and no brachytherapy capabilities. Radiating Hope, a nonprofit organization whose mission is to provide radiation therapy equipment to countries in the developing world, provided a high-dose-rate afterloading unit to the cancer center for curative cervical cancer treatment. Here we describe the implementation of high-dose-rate brachytherapy in Senegal requiring a nonstandard fractionation schedule and a novel treatment planning approach as a possible blueprint to providing this technology to other developing countries.

  7. Dosimetric study for cervix carcinoma treatment using intensity modulated radiation therapy (IMRT) compensation based on 3D intracavitary brachytherapy technique

    PubMed Central

    Yin, Gang; Wang, Pei; Lang, Jinyi; Tian, Yin; Luo, Yangkun; Fan, Zixuan

    2016-01-01

    Purpose Intensity modulated radiation therapy (IMRT) compensation based on 3D high-dose-rate (HDR) intracavitary brachytherapy (ICBT) boost technique (ICBT + IMRT) has been used in our hospital for advanced cervix carcinoma patients. The purpose of this study was to compare the dosimetric results of the four different boost techniques (the conventional 2D HDR intracavitary brachytherapy [CICBT], 3D optimized HDR intracavitary brachytherapy [OICBT], and IMRT-alone with the applicator in situ). Material and methods For 30 patients with locally advanced cervical carcinoma, after the completion of external beam radiotherapy (EBRT) for whole pelvic irradiation 45 Gy/25 fractions, five fractions of ICBT + IMRT boost with 6 Gy/fractions for high risk clinical target volume (HRCTV), and 5 Gy/fractions for intermediate risk clinical target volume (IRCTV) were applied. Computed tomography (CT) and magnetic resonance imaging (MRI) scans were acquired using an in situ CT/MRI-compatible applicator. The gross tumor volume (GTV), the high/intermediate-risk clinical target volume (HRCTV/IRCTV), bladder, rectum, and sigmoid were contoured by CT scans. Results For ICBT + IMRT plan, values of D90, D100 of HRCTV, D90, D100, and V100 of IRCTV significantly increased (p < 0.05) in comparison to OICBT and CICBT. The D2cc values for bladder, rectum, and sigmoid were significantly lower than that of CICBT and IMRT alone. In all patients, the mean rectum V60 Gy values generated from ICBT + IMRT and OICBT techniques were very similar but for bladder and sigmoid, the V60 Gy values generated from ICBT + IMRT were higher than that of OICBT. For the ICBT + IMRT plan, the standard deviations (SD) of D90 and D2cc were found to be lower than other three treatment plans. Conclusions The ICBT + IMRT technique not only provides good target coverage but also maintains low doses (D2cc) to the OAR. ICBT + IMRT is an optional technique to boost parametrial region or tumor of large size and irregular shape

  8. Co-overexpression of bcl-2 and c-myc in uterine cervix carcinomas and premalignant lesions.

    PubMed

    Protrka, Z; Arsenijevic, S; Dimitrijevic, A; Mitrovic, S; Stankovic, V; Milosavljevic, M; Kastratovic, T; Djuric, J

    2011-01-01

    To establish the role of co-overexpression of bcl-2 and c-myc protooncogenes in uterine cervix carcinogenesis, we examined 138 tissue samples of low grade cervical squamous intraepithelial lesions (SIL), high grade SIL, portio vaginalis uteri (PVU) carcinoma in situ and PVU carcinoma invasive, stage IA-IIA (study group) and 36 samples without SIL or malignancy (control group). The expression of bcl-2 and c-myc was detected immunohistochemically using a monoclonal antibody. Fisher’s exact test (P<0.05) was used to assess statistical significance. Overexpression of bcl-2 was found to increase in direct relation to the grade of the cervical lesions. High sensitivity was of great diagnostic significance for the detection of these types of changes in the uterine cervix. On the basis of high predictive values it can be said that in patients with bcl-2 overexpression there is a great possibility that they have premalignant or malignant changes in the uterine cervix. Co-overexpression of bcl-2 and c-myc oncogenes was found only in patients with PVU invasive carcinoma (6/26-23.0%). Statistically significant difference was not found in the frequency of co-overexpression in patients with PVU invasive carcinoma in relation to the control group (Fisher’s test; P=0.064). The method's sensitivity of determining these oncogenes with the aim of detecting PVU invasive carcinoma was 23%, while specificity was 72.2%. On the basis of high predictive values (100%), speaking in statistical terms, it can be concluded that all patients with co-overexpression of bcl-2 and c-myc oncogenes will have PVU invasive carcinoma. We confirmed in our research that co-overexpression of bcl-2 and c-myc oncogenes was increased only in PVU invasive carcinoma. However, a more extensive series of samples and additional tests are required to establish the prognostic significance of bcl-2 and c-myc co-overexpression in cervical carcinogenesis. PMID:21556123

  9. Intra-Arterial Infusion Chemotherapy Using Cisplatin With Radiotherapy for Stage III Squamous Cell Carcinoma of the Cervix

    SciTech Connect

    Kaneyasu, Yuko Nagai, Nobutaka; Nagata, Yasushi; Hashimoto, Yasutoshi; Yuki, Shintaro; Murakami, Yuji; Kenjo, Masahiro; Kakizawa, Hideaki; Toyota, Naoyuki; Fujiwara, Hisaya; Kudo, Yoshiki; Ito, Katsuhide

    2009-10-01

    Purpose: To examine the effectiveness of concomitant intra-arterial infusion chemotherapy (IAIC) using cisplatin (CDDP) with radiotherapy for Stage III squamous cell carcinoma of the cervix. Materials and Methods: We analyzed 29 cases of Stage III squamous cell carcinoma of the uterine cervix treated with radiotherapy and IAIC of CDDP from 1991 to 2006. External-beam therapy was given to the whole pelvis using four opposing parallel fields with an 18-MV linear accelerator unit. A central shield was used after 30-40 Gy with external whole-pelvic irradiation, and the total dose was 50 Gy. High-dose-rate brachytherapy was given with {sup 192}Ir microSelectron. The dose at Point A was 6 Gy per fraction, 2 fractions per week, and the total number of fractions was either 3 or 4. Two or three courses of IAIC were given concomitantly with CDDP 120 mg or carboplatin 300 mg. Results: We confirmed excellent medicine distribution directly by using computed tomographic angiography. The 5-year overall survival rate for Stage III patients was 62%, the cause-specific survival rate was 70%, and the local relapse-free survival rate was 89%. Local recurrence, distant metastasis, and occurrences of both were 7%, 38%, and 3%, respectively. The incidence of severe acute hematologic adverse reactions (Grade {>=}3) was 27% for all patients; however, all recovered without interruption of radiotherapy. Severe nonhematologic effects (Grade {>=}3) were 3%, including nausea and ileus. Only 1 patient's radiotherapy was interrupted for a period of 1 week because of ileus. Severe late complication rates (Grade {>=}3) for the bladder, rectum, and intestine were 3%, 3%, and 10%, respectively. Conclusion: A combination of IAIC and systemic chemotherapy should be considered to improve the prognosis of patients with Stage III squamous cell carcinoma of the cervix.

  10. The dosimetric impact of different photon beam energy on RapidArc radiotherapy planning for cervix carcinoma

    PubMed Central

    Kumar, Lalit; Yadav, Girigesh; Raman, Kothanda; Bhushan, Manindra; Pal, Manoj

    2015-01-01

    The main purpose of this study is to know the effect of three different photon energies viz., 6, 10, and 15 mega voltage (MV) on RapidArc (RA) planning for deep-seated cervix tumor and to develop clinically acceptable RA plans with suitable photon energy. RA plans were generated for 6, 10, and 15 MV photon energies for twenty patients reported with cervix carcinoma. RA plans were evaluated in terms of planning target volume (PTV) coverage, dose to organs at risk (OARs), conformity index (CI), homogeneity index (HI), gradient measure, external volume index of dose distribution produced, total number of monitor units (MUs), nontumor integral dose (ID), and low dose volume of normal tissue. A two-sample paired t-test was performed to compare the dosimetric parameters of RA plans. Irrespective of photon energy used for RA planning, plans were dosimetrically similar in terms of PTV coverage, OARs sparing, CI and HI. The numbers of MUs were 13.4 ± 1.4% and 18.2 ± 1.5% higher and IDs were 2.7 ± 0.8% and 3.7 ± 0.9% higher in 6 MV plans in comparison to that in the 10 and 15 MV plans, respectively. V1Gy, V2Gy, V3Gy, and V4Gy were higher in 6 MV plans in comparison to that in 10 and 15 MV plans. Based on this study, 6 MV photon beam is a good choice for RA planning in case of cervix carcinoma, as it does not deliver additional exposure to patients caused by photoneutrons produced in high energy beams. PMID:26865756

  11. Bladder–Rectum Spacer Balloon in High-Dose-Rate Brachytherapy in Cervix Carcinoma

    SciTech Connect

    Rai, Bhavana; Patel, Firuza D.; Chakraborty, Santam; Sharma, Suresh C.; Kapoor, Rakesh; Aprem, Abi Santhosh

    2013-04-01

    Purpose: To compare bladder and rectum doses with the use of a bladder–rectum spacer balloon (BRSB) versus standard gauze packing in the same patient receiving 2 high-dose-rate intracavitary brachytherapy fractions. Methods and Materials: This was a randomized study to compare the reduction in bladder and rectum doses with the use of a BRSB compared with standard gauze packing in patients with carcinoma of the cervix being treated with high-dose-rate intracavitary brachytherapy. The patients were randomized between 2 arms. In arm A, vaginal packing was done with standard gauze packing in the first application, and BRSB was used in the second application. Arm B was the reverse of arm A. The International Commission for Radiation Units and Measurement (ICRU) point doses and doses to 0.1-cm{sup 3}, 1-cm{sup 3}, 2-cm{sup 3}, 5-cm{sup 3}, and 10-cm{sup 3} volumes of bladder and rectum were compared. The patients were also subjectively assessed for the ease of application and the time taken for application. Statistical analysis was done using the paired t test. Results: A total of 43 patients were enrolled; however, 3 patients had to be excluded because the BRSB could not be inserted owing to unfavorable local anatomy. Thus 40 patients (80 plans) were evaluated. The application was difficult in 3 patients with BRSB, and in 2 patients with BRSB the application time was prolonged. There was no significant difference in bladder doses to 0.1 cm{sup 3}, 1 cm{sup 3}, 2 cm{sup 3}, 5 cm{sup 3}, and 10 cm{sup 3} and ICRU bladder point. Statistically significant dose reductions to 0.1-cm{sup 3}, 1-cm{sup 3}, and 2-cm{sup 3} volumes for rectum were observed with the BRSB. No significant differences in 5-cm{sup 3} and 10-cm{sup 3} volumes and ICRU rectum point were observed. Conclusion: A statistically significant dose reduction was observed for small high-dose volumes in rectum with the BRSB. The doses to bladder were comparable for BRSB and gauze packing. Transparent balloons of

  12. Cervix Disorders

    MedlinePlus

    ... changes to the cells of the cervix, including cervical cancer. Other problems with the cervix include: Cervicitis - ... the cervix. This is usually from an infection. Cervical incompetence - This can happen during pregnancy. The opening ...

  13. Osteoclastic giant cell rich squamous cell carcinoma of the uterine cervix: a case report and review of the literature.

    PubMed

    Alemán-Meza, Lucía; Gómez-Macías, Gabriela Sofía; Barboza-Quintana, Oralia; Garza-Guajardo, Raquel; Loya-Solis, Abelardo

    2014-01-01

    Cervical carcinoma is the most common malignancy of the female genital tract and represents the second most common malignancy in women worldwide. Histologically 85 to 90% of cervical cancers are squamous cell carcinoma. Osteoclastic giant cell rich squamous cell carcinoma is an unusual histological variant of which only 4 cases have been reported. We present the case of a 49-year-old woman with a 6-month history of irregular vaginal bleeding. Examination revealed a 2.7 cm polypoid mass in the anterior lip of the uterine cervix. The patient underwent hysterectomy with bilateral salpingo-oophorectomy. Microscopically the tumor was composed of infiltrative nests of poorly differentiated nonkeratinizing squamous cell carcinoma. Interspersed in between these tumor cells were numerous osteoclastic giant cells with abundant eosinophilic cytoplasm devoid of nuclear atypia, hyperchromatism, or mitotic activity. Immunohistochemistry was performed; CK and P63 were strongly positive in the squamous component and negative in the osteoclastic giant cells, while CD68 and Vimentin were strongly positive in the giant cell population and negative in the squamous component. The patient received chemo- and radiotherapy for recurrent disease identified 3 months later on a follow-up CT scan; 7 months after the surgical procedure the patient is clinically and radiologically disease-free.

  14. Osteoclastic Giant Cell Rich Squamous Cell Carcinoma of the Uterine Cervix: A Case Report and Review of the Literature

    PubMed Central

    Alemán-Meza, Lucía; Gómez-Macías, Gabriela Sofía; Barboza-Quintana, Oralia; Garza-Guajardo, Raquel; Loya-Solis, Abelardo

    2014-01-01

    Cervical carcinoma is the most common malignancy of the female genital tract and represents the second most common malignancy in women worldwide. Histologically 85 to 90% of cervical cancers are squamous cell carcinoma. Osteoclastic giant cell rich squamous cell carcinoma is an unusual histological variant of which only 4 cases have been reported. We present the case of a 49-year-old woman with a 6-month history of irregular vaginal bleeding. Examination revealed a 2.7 cm polypoid mass in the anterior lip of the uterine cervix. The patient underwent hysterectomy with bilateral salpingo-oophorectomy. Microscopically the tumor was composed of infiltrative nests of poorly differentiated nonkeratinizing squamous cell carcinoma. Interspersed in between these tumor cells were numerous osteoclastic giant cells with abundant eosinophilic cytoplasm devoid of nuclear atypia, hyperchromatism, or mitotic activity. Immunohistochemistry was performed; CK and P63 were strongly positive in the squamous component and negative in the osteoclastic giant cells, while CD68 and Vimentin were strongly positive in the giant cell population and negative in the squamous component. The patient received chemo- and radiotherapy for recurrent disease identified 3 months later on a follow-up CT scan; 7 months after the surgical procedure the patient is clinically and radiologically disease-free. PMID:25587478

  15. Lymph node metastasis and lymph vascular space invasion in microinvasive squamous cell carcinoma of the uterine cervix.

    PubMed

    Lee, K B M; Lee, J M; Park, C Y; Lee, K B; Cho, H Y; Ha, S Y

    2006-01-01

    The objective of this study was to determine whether the depth of invasion was related to lymph vascular space invasion (LVSI) and lymph node metastasis and whether there was a correlation between LVSI and lymph node metastasis in stage IA cervical cancer. The medical records, including surgical notes and pathologic reports, of 202 patients with microinvasive squamous cell carcinoma of the uterine cervix were reviewed retrospectively. There was a positive correlation between the depth of invasion and the LVSI, and the incidence of lymph node metastasis was slightly higher than those reported hitherto for stage IA1 cervical cancer, especially in the depth of invasion of 1-3 mm group. However, among four patients with lymph node metastasis, only two patients had positive LVSI. There was no definite correlation between LVSI and lymph node metastasis. LVSI could not identify the patients with high risk for lymph node metastasis.

  16. Phase I-II clinical trial of Californium-252. Treatment of stage IB carcinoma of the cervix.

    PubMed

    Maruyama, Y; VanNagell, J R; Yoneda, J; Donaldson, E; Gallion, H; Rowley, K; Kryscio, R; Beach, J L

    1987-04-15

    Intracavitary Californium-252 combined with whole-pelvis photon radiotherapy was tested as the sole form of treatment for 22 patients with Stage IB carcinoma of the cervix. Californium-252 (Cf) is a fast neutron-emitting radioisotope currently being tested in trials of neutron brachytherapy (NT). The outcomes of the treated group of patients were traced for local tumor control, survival, patterns of failure, and complications. The Cf intracavitary therapy combined with whole-pelvis photon radiotherapy resulted in 95% 2-year and 91% 5-year actuarial survival. There were 9% Grade II-III complications by the Stockholm scale and 4% local failures. These results were obtained in an early clinical trial with a group of largely poor-risk patients with tumors of mean diameter of 4.3 cm.

  17. Challenges of advanced hepatocellular carcinoma.

    PubMed

    Colagrande, Stefano; Inghilesi, Andrea L; Aburas, Sami; Taliani, Gian G; Nardi, Cosimo; Marra, Fabio

    2016-09-14

    Hepatocellular carcinoma (HCC) is an aggressive malignancy, resulting as the third cause of death by cancer each year. The management of patients with HCC is complex, as both the tumour stage and any underlying liver disease must be considered conjointly. Although surveillance by imaging, clinical and biochemical parameters is routinely performed, a lot of patients suffering from cirrhosis have an advanced stage HCC at the first diagnosis. Advanced stage HCC includes heterogeneous groups of patients with different clinical condition and radiological features and sorafenib is the only approved treatment according to Barcelona Clinic Liver Cancer. Since the introduction of sorafenib in clinical practice, several phase III clinical trials have failed to demonstrate any superiority over sorafenib in the frontline setting. Loco-regional therapies have also been tested as first line treatment, but their role in advanced HCC is still matter of debate. No single agent or combination therapies have been shown to impact outcomes after sorafenib failure. Therefore this review will focus on the range of experimental therapeutics for patients with advanced HCC and highlights the successes and failures of these treatments as well as areas for future development. Specifics such as dose limiting toxicity and safety profile in patients with liver dysfunction related to the underlying chronic liver disease should be considered when developing therapies in HCC. Finally, robust validated and reproducible surrogate end-points as well as predictive biomarkers should be defined in future randomized trials. PMID:27678348

  18. Challenges of advanced hepatocellular carcinoma

    PubMed Central

    Colagrande, Stefano; Inghilesi, Andrea L; Aburas, Sami; Taliani, Gian G; Nardi, Cosimo; Marra, Fabio

    2016-01-01

    Hepatocellular carcinoma (HCC) is an aggressive malignancy, resulting as the third cause of death by cancer each year. The management of patients with HCC is complex, as both the tumour stage and any underlying liver disease must be considered conjointly. Although surveillance by imaging, clinical and biochemical parameters is routinely performed, a lot of patients suffering from cirrhosis have an advanced stage HCC at the first diagnosis. Advanced stage HCC includes heterogeneous groups of patients with different clinical condition and radiological features and sorafenib is the only approved treatment according to Barcelona Clinic Liver Cancer. Since the introduction of sorafenib in clinical practice, several phase III clinical trials have failed to demonstrate any superiority over sorafenib in the frontline setting. Loco-regional therapies have also been tested as first line treatment, but their role in advanced HCC is still matter of debate. No single agent or combination therapies have been shown to impact outcomes after sorafenib failure. Therefore this review will focus on the range of experimental therapeutics for patients with advanced HCC and highlights the successes and failures of these treatments as well as areas for future development. Specifics such as dose limiting toxicity and safety profile in patients with liver dysfunction related to the underlying chronic liver disease should be considered when developing therapies in HCC. Finally, robust validated and reproducible surrogate end-points as well as predictive biomarkers should be defined in future randomized trials.

  19. Challenges of advanced hepatocellular carcinoma

    PubMed Central

    Colagrande, Stefano; Inghilesi, Andrea L; Aburas, Sami; Taliani, Gian G; Nardi, Cosimo; Marra, Fabio

    2016-01-01

    Hepatocellular carcinoma (HCC) is an aggressive malignancy, resulting as the third cause of death by cancer each year. The management of patients with HCC is complex, as both the tumour stage and any underlying liver disease must be considered conjointly. Although surveillance by imaging, clinical and biochemical parameters is routinely performed, a lot of patients suffering from cirrhosis have an advanced stage HCC at the first diagnosis. Advanced stage HCC includes heterogeneous groups of patients with different clinical condition and radiological features and sorafenib is the only approved treatment according to Barcelona Clinic Liver Cancer. Since the introduction of sorafenib in clinical practice, several phase III clinical trials have failed to demonstrate any superiority over sorafenib in the frontline setting. Loco-regional therapies have also been tested as first line treatment, but their role in advanced HCC is still matter of debate. No single agent or combination therapies have been shown to impact outcomes after sorafenib failure. Therefore this review will focus on the range of experimental therapeutics for patients with advanced HCC and highlights the successes and failures of these treatments as well as areas for future development. Specifics such as dose limiting toxicity and safety profile in patients with liver dysfunction related to the underlying chronic liver disease should be considered when developing therapies in HCC. Finally, robust validated and reproducible surrogate end-points as well as predictive biomarkers should be defined in future randomized trials. PMID:27678348

  20. Radiation dose delivery verification in the treatment of carcinoma-cervix

    SciTech Connect

    Shrotriya, D. Srivastava, R. N. L.; Kumar, S.

    2015-06-24

    The accurate dose delivery to the clinical target volume in radiotherapy can be affected by various pelvic tissues heterogeneities. An in-house heterogeneous woman pelvic phantom was designed and used to verify the consistency and computational capability of treatment planning system of radiation dose delivery in the treatment of cancer cervix. Oncentra 3D-TPS with collapsed cone convolution (CCC) dose calculation algorithm was used to generate AP/PA and box field technique plan. the radiation dose was delivered by Primus Linac (Siemens make) employing high energy 15 MV photon beam by isocenter technique. A PTW make, 0.125cc ionization chamber was used for direct measurements at various reference points in cervix, bladder and rectum. The study revealed that maximum variation between computed and measured dose at cervix reference point was 1% in both the techniques and 3% and 4% variation in AP/PA field and 5% and 4.5% in box technique at bladder and rectum points respectively.

  1. Radiation dose delivery verification in the treatment of carcinoma-cervix

    NASA Astrophysics Data System (ADS)

    Shrotriya, D.; Kumar, S.; Srivastava, R. N. L.

    2015-06-01

    The accurate dose delivery to the clinical target volume in radiotherapy can be affected by various pelvic tissues heterogeneities. An in-house heterogeneous woman pelvic phantom was designed and used to verify the consistency and computational capability of treatment planning system of radiation dose delivery in the treatment of cancer cervix. Oncentra 3D-TPS with collapsed cone convolution (CCC) dose calculation algorithm was used to generate AP/PA and box field technique plan. the radiation dose was delivered by Primus Linac (Siemens make) employing high energy 15 MV photon beam by isocenter technique. A PTW make, 0.125cc ionization chamber was used for direct measurements at various reference points in cervix, bladder and rectum. The study revealed that maximum variation between computed and measured dose at cervix reference point was 1% in both the techniques and 3% and 4% variation in AP/PA field and 5% and 4.5% in box technique at bladder and rectum points respectively.

  2. Targeted PI3K/AKT/mTOR therapy for metastatic carcinomas of the cervix: A phase I clinical experience

    PubMed Central

    Hou, Ming-Mo; Liu, Xiaochun; Wheler, Jennifer; Naing, Aung; Hong, David; Coleman, Robert L.; Tsimberidou, Apostolia; Janku, Filip; Zinner, Ralph; Lu, Karen; Kurzrock, Razelle; Fu, Siqing

    2014-01-01

    Background Activated PI3K/AKT/mTOR pathway frequently occurs in metastatic or recurrent cervical carcinomas. However, the clinical benefits of matched therapy, a therapeutic approach targeting a specific mutational abnormality, have not yet been established. Methods We analyzed the outcomes of patients with metastatic or recurrent cervical carcinomas who had a test for PIK3CA mutation and/or PTEN loss/mutation, and received ≥1 phase I therapeutic regimen between January 2006 and June 2013. Results Patients with adenocarcinoma had fewer PIK3CA mutations (14%), and survived longer (median, 14.2 months) than those with squamous cell carcinoma (48% and 7.2 months; p = 0.016, and 0.001, respectively). Matched therapy targeting the activated PI3K/AKT/mTOR pathway led to a favorable rate of SD ≥ 6 months/CR/PR (53%) and significantly longer progression-free survival (median, 6.0 months) than non-matched therapy (11% and 1.5 months; p = 0.08 and 0.026; respectively). In patients with squamous cell carcinoma of the cervix, the presence of PIK3CA mutations was associated with a significantly longer overall survival (median, 9.4 months) than the absence of PIK3CA mutations (median, 4.2 months; p = 0.019). Conclusions Matched therapy targeting the activated PI3K/AKT/mTOR pathway provided meaningful clinical benefits. Thus, further evaluation of PI3K/AKT/mTOR pathway targeted therapy is warranted, especially in metastatic or recurrent squamous cell carcinoma. PMID:25426553

  3. Preoperative external beam radiotherapy and reduced dose brachytherapy for carcinoma of the cervix: survival and pathological response

    PubMed Central

    Jacinto, Alexandre A; Castilho, Marcus S; Novaes, Paulo ERS; Novick, Pablo R; Viani, Gustavo A; Salvajoli, João V; Ferrigno, Robson; Pellizzon, Antonio Cássio A; Lima, Stella SS; Maia, Maria AC; Fogaroli, Ricardo C

    2007-01-01

    Purpose To evaluate the pathologic response of cervical carcinoma to external beam radiotherapy (EBRT) and high dose rate brachytherapy (HDRB) and outcome. Materials and methods Between 1992 and 2001, 67 patients with cervical carcinoma were submitted to preoperative radiotherapy. Sixty-five patients were stage IIb. Preoperative treatment included 45 Gy EBRT and 12 Gy HDRB. Patients were submitted to surgery after a mean time of 82 days. Lymphadenectomy was performed in 81% of patients. Eleven patients with residual cervix residual disease on pathological specimen were submitted to 2 additional insertions of HDRB. Results median follow up was 72 months. Five-year cause specific survival was 75%, overall survival 65%, local control 95%. Complete pelvic pathological response was seen in 40%. Surgery performed later than 80 days was associated with pathological response. Pelvic nodal involvement was found in 12%. Complete pelvic pathological response and negative lymphnodes were associated with better outcome (p = .03 and p = .005). Late grade 3 and 4 urinary and intestinal adverse effects were seen in 12 and 2% of patients. Conclusion Time allowed between RT and surgery correlated with pathological response. Pelvic pathological response was associated with improved outcome. Postoperative additional HDRB did not improve therapeutic results. Treatment was well tolerated. PMID:17316435

  4. Differences in the ARID-1 alpha expressions in squamous and adenosquamous carcinomas of uterine cervix.

    PubMed

    Solakoglu Kahraman, Dudu; Diniz, Gulden; Sayhan, Sevil; Ayaz, Duygu; Uncel, Melek; Karadeniz, Tugba; Akman, Tulay; Ozdemir, Aykut

    2015-10-01

    AT-rich interactive domain 1A (ARID1A) is a tumor suppressor gene involved in chromatin remodeling which encodes ARID1A (BAF250a) protein. Recent studies have shown the loss of ARID1A expression in several types of tumors. This retrospective study was designed to evaluate the differences in tissue expressions of ARID1A in a spectrum of cervical neoplasms. Cervical intraepithelial neoplasms, invasive squamous or adenosquamous carcinomas were identified in 100 patients recently diagnosed as cervical neoplasms based on pathology databases. In this series, there were 29 low- and 29 high-grade cervical intraepithelial neoplasms, 27 squamous cell carcinomas, and 15 adenosquamous carcinomas. Mean age of the patients was 47.8 ± 13 years (20-80 years). It was determined that the expression of ARID1A was statistically significantly down-regulated in adenosquamous carcinomas when compared with non-invasive or invasive squamous cell carcinomas (p = 0.015). Lower levels of the ARID1A expression were detected in cases with adenosquamous carcinomas (60%), low- or high-grade squamous intraepithelial lesion (SIL) (31%), and squamous cell carcinomas (18.5%). Our findings have demonstrated the presence of a correlation between ARID1A expression and adenomatous differentiation of uterine squamous cell carcinomas. Therefore, ARID1A gene may suggestively have a role in the pathogenesis of cervical adenosquamous carcinomas.

  5. Intracavitary irradiation of carcinomas of the uterus and cervix: the Creteil method

    SciTech Connect

    Pierquin, B.; Marinello, G.; Mege, J.P.; Crook, J.

    1988-12-01

    The Creteil method is a logical and simple system for intracavitary therapy of cervical and uterine cancer. The system is based on the use of a plastic cervico-vaginal moulage loaded with 0.5 mm diameter iridium 192 wire sources. The dimensions of both the moulage and the sources correspond to the size of the cervix being treated according to precisely defined relationships. The dose is specified on a reference isodose of a fixed value enclosing the pear-shaped target volume whose dimensions depend on the geometry of the sources. Source geometry in turn, depends on the size of the cervix. Thus, the dimensions of the target volume can be accurately predicted at the time of the application. Furthermore, treatment can be performed in a single application, with all sources having the same linear reference air kerma rate (or activity). Radioprotective measures are simple but effective and the patient is not subjected to the restrictions imposed by attachment to an after-loading apparatus. Our clinical results for early Stage T1 and T2a cervical tumors show excellent local control without major treatment complications or long term sequelae.

  6. Clinical Behaviors and Outcomes for Adenocarcinoma or Adenosquamous Carcinoma of Cervix Treated by Radical Hysterectomy and Adjuvant Radiotherapy or Chemoradiotherapy

    SciTech Connect

    Huang, Yi-Ting; Wang, Chun-Chieh; Tsai, Chien-Sheng; Lai, Chyong-Huey; Chang, Ting-Chang; Chou, Hung-Hsueh; Lee, Steve P.; Hong, Ji-Hong

    2012-10-01

    Purpose: To compare clinical behaviors and treatment outcomes between patients with squamous cell carcinoma (SCC) and adenocarcinoma/adenosquamous carcinoma (AC/ASC) of the cervix treated with radical hysterectomy (RH) and adjuvant radiotherapy (RT) or concurrent chemoradiotherapy (CCRT). Methods and Materials: A total of 318 Stage IB-IIB cervical cancer patients, 202 (63.5%) with SCC and 116 (36.5%) with AC/ASC, treated by RH and adjuvant RT/CCRT, were included. The indications for RT/CCRT were deep stromal invasion, positive resection margin, parametrial invasion, or lymph node (LN) metastasis. Postoperative CCRT was administered in 65 SCC patients (32%) and 80 AC/ASC patients (69%). Patients with presence of parametrial invasion or LN metastasis were stratified into a high-risk group, and the rest into an intermediate-risk group. The patterns of failure and factors influencing survival were evaluated. Results: The treatment failed in 39 SCC patients (19.3%) and 39 AC/ASC patients (33.6%). The 5-year relapse-free survival rates for SCC and AC/ASC patients were 83.4% and 66.5%, respectively (p = 0.000). Distant metastasis was the major failure pattern in both groups. After multivariate analysis, prognostic factors for local recurrence included younger age, parametrial invasion, AC/ASC histology, and positive resection margin; for distant recurrence they included parametrial invasion, LN metastasis, and AC/ASC histology. Compared with SCC patients, those with AC/ASC had higher local relapse rates for the intermediate-risk group but a higher distant metastasis rate for the high-risk group. Postoperative CCRT tended to improve survival for intermediate-risk but not for high-risk AC/ASC patients. Conclusions: Adenocarcinoma/adenosquamous carcinoma is an independent prognostic factor for cervical cancer patients treated by RH and postoperative RT. Concurrent chemoradiotherapy could improve survival for intermediate-risk, but not necessarily high-risk, AC/ASC patients.

  7. Cervix cryosurgery

    MedlinePlus

    ... enough to freeze and destroy the tissue. An "ice ball" forms on the cervix, killing the abnormal cells. For the treatment to be most effective: The freezing is done for 3 minutes The cervix is ...

  8. New advances in hepatocellular carcinoma.

    PubMed

    Pascual, Sonia; Herrera, Iván; Irurzun, Javier

    2016-03-28

    Hepatocellular carcinoma (HCC) is the leading cause of deaths in cirrhotic patients and the third cause of cancer related deaths. Most HCC are associated with well known underlying risk factors, in fact, HCC arise in cirrhotic patients in up to 90% of cases, mainly due to chronic viral hepatitis and alcohol abuse. The worldwide prevention strategies are conducted to avoid the infection of new subjects and to minimize the risk of liver disease progression in infected patients. HCC is a condition which lends itself to surveillance as at-risk individuals can readily be identified. The American and European guidelines recommended implementation of surveillance programs with ultrasound every six months in patient at-risk for developing HCC. The diagnosis of HCC can be based on non-invasive criteria (only in cirrhotic patient) or pathology. Accurately staging patients is essential to oncology practice. The ideal tumour staging system in HCC needs to account for both tumour characteristics and liver function. Treatment allocation is based on several factors: Liver function, size and number of tumours, macrovascular invasion or extrahepatic spread. The recommendations in terms of selection for different treatment strategies must be based on evidence-based data. Resection, liver transplant and interventional radiology treatment are mainstays of HCC therapy and achieve the best outcomes in well-selected candidates. Chemoembolization is the most widely used treatment for unresectable HCC or progression after curative treatment. Finally, in patients with advanced HCC with preserved liver function, sorafenib is the only approved systemic drug that has demonstrated a survival benefit and is the standard of care in this group of patients. PMID:27028578

  9. New advances in hepatocellular carcinoma

    PubMed Central

    Pascual, Sonia; Herrera, Iván; Irurzun, Javier

    2016-01-01

    Hepatocellular carcinoma (HCC) is the leading cause of deaths in cirrhotic patients and the third cause of cancer related deaths. Most HCC are associated with well known underlying risk factors, in fact, HCC arise in cirrhotic patients in up to 90% of cases, mainly due to chronic viral hepatitis and alcohol abuse. The worldwide prevention strategies are conducted to avoid the infection of new subjects and to minimize the risk of liver disease progression in infected patients. HCC is a condition which lends itself to surveillance as at-risk individuals can readily be identified. The American and European guidelines recommended implementation of surveillance programs with ultrasound every six months in patient at-risk for developing HCC. The diagnosis of HCC can be based on non-invasive criteria (only in cirrhotic patient) or pathology. Accurately staging patients is essential to oncology practice. The ideal tumour staging system in HCC needs to account for both tumour characteristics and liver function. Treatment allocation is based on several factors: Liver function, size and number of tumours, macrovascular invasion or extrahepatic spread. The recommendations in terms of selection for different treatment strategies must be based on evidence-based data. Resection, liver transplant and interventional radiology treatment are mainstays of HCC therapy and achieve the best outcomes in well-selected candidates. Chemoembolization is the most widely used treatment for unresectable HCC or progression after curative treatment. Finally, in patients with advanced HCC with preserved liver function, sorafenib is the only approved systemic drug that has demonstrated a survival benefit and is the standard of care in this group of patients. PMID:27028578

  10. The value of loop electrosurgical conization in the treatment of stage IA1 microinvasive carcinoma of the uterine cervix.

    PubMed

    Bekkers, R L M; Keyser, K G G; Bulten, J; Hanselaar, A G J M; Schijf, C P T; Boonstra, H; Massuger, L F A G

    2002-01-01

    The objective of this study is to assess the value of Loop Electrosurgical Conization (LEC) in the treatment of stage IA1 microinvasive squamous cell carcinoma (MIC) of the uterine cervix. Retrospectively, 82 patients with FIGO stage IA1 MIC, primarily treated with LEC on see and treat basis, were analyzed. After the initial LEC, 16 patients received cytologic and colposcopic follow-up only, 66 patients underwent a second procedure (repeat LEC, Cold Knife Conization (CKC), or hysterectomy), and four patients underwent a third procedure (hysterectomy). In 63 patients (77%) no residual CIN 3 or MIC was present after the initial LEC. Treatment of residual CIN 3 or MIC was equally effective with a repeat LEC as with CKC. One patient defaulted follow-up and developed a recurrence in the vaginal vault and was treated with a radical hysterectomy. LEC can be used as an alternative for CKC in treatment of patients with stage IA1 MIC. The advantage of LEC is that it can be performed as an outpatient procedure in addition to a diagnostic colposcopy and does not require a major anesthetic. Only a small number of patients will need a more extensive procedure. PMID:12366667

  11. A retrospective study of the effects of pelvic irradiation for carcinoma of the cervix on gastrointestinal function

    SciTech Connect

    Yeoh, E.; Ahmad, A.; Horowitz, M.; Russo, A.; Muecke, T.; Chatterton, B. ); Robb, T. )

    1993-03-20

    The purpose of the study was to evaluate the prevalence of disordered gastrointestinal function following therapeutic irradiation. Gastrointestinal function was evaluated in 30 randomly selected patients who had received pelvic irradiation for treatment of carcinoma of the cervix between 1 and 6 years previously. Each patient underwent evaluations of (a) gastrointestinal symptoms (b) absorption of bile acid, vitamin B12, lactose and fat (c) gastrointestinal transit: gastric emptying, small intestinal transit and whole gut transit and (d) intestinal permeability. Results were compared with those obtained in 18 normal volunteers. Stool frequency was above the control range in five patients and had increased (p < 0.001) since radiotherapy treatment. Bile acid (p<0.001) vitamin B12(p<0.01) and lactose (p<0.01) absorption were less in the patients when compared with the control subjects. Bile acid adsorption was below the control range in 14 of the 30 patients. Dietary calcium intake was lower (p<0.05) in those patients with lactose malabsorption. Gastric emptying (p<0.01) and small intestinal transit (p<0.01) were more rapid in the patients. Both small intestinal (r=-0.39, p<0.05) and whole gut (r=-0.45) transit were inversely related to stool frequency. Either bowel frequency, bile acid adsorption, vitamin B12 absorption was outside the control range in 19 of the 30 patients. Abnormal gastrointestinal function is essentially an inevitable long-term sequel of pelvic irradiation. 41 refs., 4 figs., 3 tabs.

  12. Early changes in flow cytometric DNA profiles induced by californium-252 neutron brachytherapy in squamocellular carcinomas of the uterine cervix.

    PubMed

    Tacev, T; Zaloudík, J; Janáková, L; Vagunda, V

    1998-01-01

    Ninety-five squamocellular carcinomas of the uterine cervix, clinical Stages II and III, were treated by either four schedules combining 252-californium neutron-gamma-radiotherapy with different proportions of a neutron component (9, 6 and 3 Gy) or gamma-irradiation alone. Flow cytometric DNA profiles were obtainable in 72 cases before treatment and 56 cases were monitored for DNA content by flow cytometry (FCM) in weekly intervals by analysis of sequential microbiopsies for one month during and after radiotherapy. DNA aneuploidy was reduced from 40% (25/63) to 19% (9/47) one week within therapy in neutron-treated groups, but not after initial gamma-radiotherapy alone. Extinction of DNA aneuploid subpopulations occurred after neutron therapy in all remaining aneuploid tumors (9/9) during further monitoring, but only in 40% (2/5) of tumors after sole gamma-irradiation. In contrast, proliferation index by more than 50% was more often achieved in groups with a higher gamma-radiation component than after neutrons only. When all therapy-induced DNA flow cytometric events are taken together for evaluation of the effects of various radiotherapy schedules, it appears that the regimen with the maximal neutron dose may not be optimal for all tumors. It is hypothesized that the differences in the early flow cytometric DNA profiles may select the DNA aneuploid squamous cell uterine cervical carcinomas as candidates for combined neutron-brachytherapy, while highly proliferating DNA near-diploid tumors may profit more from treatment with a higher gamma-radiotherapy component. However, these early DNA flow cytometric findings need to be correlated with clinical course of the disease to validate this hypothesis, a process which will be completed at the end of the expected five-year clinical outcome in 2000.

  13. Large-cell neuroendocrine carcinoma of the uterine cervix complicating pregnancy.

    PubMed

    Li, William W H; Yau, T N; Leung, Carmen W L; Pong, W M; Chan, May Y M

    2009-02-01

    Large-cell neuroendocrine cervical carcinoma is a rare and aggressive cancer that tends to spread and recur early despite intensive multimodal treatment. The optimal mode of therapy is still controversial and management during pregnancy is challenging because foetal well-being must also be considered. We report a patient with clinically stage IIB large-cell neuroendocrine cervical carcinoma who presented with a cervical polyp and vaginal bleeding at 18 weeks of pregnancy. The patient received concurrent chemotherapy and radiation after termination of pregnancy and remained in complete remission 21 months after completion of treatment.

  14. Cancer of the cervix

    SciTech Connect

    Thompson, L.J. )

    1990-08-01

    Since the introduction of the Papanicolaou smear and colposcopy, cervical cancers can be diagnosed and treated easily in their preinvasive state. Although theoretically cancer of the cervix should be detected and treated before becoming invasive disease, there are still too many women who develop invasive cancer of the cervix and require radical surgery and/or radiation therapy. The management of patients with recurrent or advanced disease is difficult and challenging.36 references.

  15. Loss of heterozygosity for defined regions on chromosomes 3, 11 and 17 in carcinomas of the uterine cervix.

    PubMed Central

    Kersemaekers, A. M.; Hermans, J.; Fleuren, G. J.; van de Vijver, M. J.

    1998-01-01

    Loss of heterozygosity (LOH) frequently occurs in squamous cell carcinomas of the uterine cervix and indicates the probable sites of tumour-suppressor genes that play a role in the development of this tumour. To define the localization of these tumour-suppressor genes, we studied loss of heterozygosity in 64 invasive cervical carcinomas (stage IB and IIA) using the polymerase chain reaction with 24 primers for polymorphic repeats of known chromosomal localization. Chromosomes 3, 11, 13, 16 and 17, in particular, were studied. LOH was frequently found on chromosome 11, in particular at 11q22 (46%) and 11q23.3 (43%). LOH on chromosome 11p was not frequent. On chromosome 17p13.3, a marker (D17S513) distal to p53 showed 38% LOH, whereas p53 itself showed only 20% LOH. On the short arm of chromosome 3, LOH was frequently found (41%) at 3p21.1. The beta-catenin gene is located in this chromosomal region. Therefore, expression of beta-catenin protein was studied in 39 cases using immunohistochemistry. Staining of beta-catenin at the plasma membrane of tumour cells was present in 38 cases and completely absent in only one case. The tumour-suppressor gene on chromosome 3p21.1 may be beta-catenin in this one case, but (an)other tumour-suppressor gene(s) must also be present in this region. For the other chromosomes studied, 13q (BRCA-2) and 16q (E-cadherin), only sporadic losses (< 15% of cases) were found. Expression of E-cadherin was found in all of 37 cases but in six cases the staining was very weak. No correlation was found between clinical and histological parameters and losses on chromosome 3p, 11q and 17p. In addition to LOH, microsatellite instability was found in one tumour for almost all loci and in eight tumours for one to three loci. In conclusion, we have identified three loci with frequent LOH, which may harbour new tumour-suppressor genes, and found microsatellite instability in 14% of cervical carcinomas. Images Figure 1 Figure 4 Figure 5 PMID:9460988

  16. Characterization of human papillomavirus type 66 from an invasive carcinoma of the uterine cervix.

    PubMed Central

    Tawheed, A R; Beaudenon, S; Favre, M; Orth, G

    1991-01-01

    Human papillomavirus (HPV) DNA sequences coexisting with HPV16 and HPV45 were cloned from an invasive cervical carcinoma. The cloned HPV was shown to be a novel type, named HPV66, and is related to HPV56 (an HPV detected in cervical cancer). After screening 160 anogenital biopsies, four specimens exhibited histological features of intraepithelial neoplasia and contained HPV66 sequences. Of these, three were found to be associated with another HPV type. Images PMID:1663515

  17. Progression of naive intraepithelial neoplasia genome to aggressive squamous cell carcinoma genome of uterine cervix

    PubMed Central

    Kim, Min Sung; Baek, In-Pyo; Lee, Sung Hak; Lee, Ah Won; Hur, Soo Young; Kim, Tae-Min; Lee, Sug Hyung; Chung, Yeun-Jun

    2015-01-01

    Although cervical intraepithelial neoplasia (CIN) is considered a neoplasia, its genomic alterations remain unknown. For this, we performed whole-exome sequencing and copy number profiling of three CINs, a microinvasive carcinoma (MIC) and four cervical squamous cell carcinomas (CSCC). Both total mutation and driver mutation numbers of the CINs were significantly fewer than those of the MIC/CSCCs (P = 0.036 and P = 0.018, respectively). Importantly, PIK3CA was altered in all MIC/CSCCs by either mutation or amplification, but not in CINs. The CINs harbored significantly lower numbers of copy number alterations (CNAs) than the MIC/CSCCs as well (P = 0.036). Pathway analysis predicted that the MIC/CSCCs were enriched with cancer-related signalings such as cell adhesion, mTOR signaling pathway and cell migration that were depleted in the CINs. The mutation-based estimation of evolutionary ages identified that CIN genomes were younger than MIC/CSCC genomes. The data indicate that CIN genomes harbor unfixed mutations in addition to human papilloma virus infection but require additional driver hits such as PIK3CA, TP53, STK11 and MAPK1 mutations for CSCC progression. Taken together, our data may explain the long latency from CIN to CSCC progression and provide useful information for molecular diagnosis of CIN and CSCC. PMID:25738363

  18. Utility of GATA3 immunohistochemistry in differentiating urothelial carcinoma from prostate adenocarcinoma and squamous cell carcinomas of the uterine cervix, anus, and lung.

    PubMed

    Chang, Alex; Amin, Ali; Gabrielson, Edward; Illei, Peter; Roden, Richard B; Sharma, Rajni; Epstein, Jonathan I

    2012-10-01

    Distinguishing invasive high-grade urothelial carcinoma (UC) from other carcinomas occurring in the genitourinary tract may be difficult. The differential diagnosis includes high-grade prostatic adenocarcinoma, spread from an anal squamous cell carcinoma (SCC), or spread from a uterine cervical SCC. In terms of metastatic UC, the most common problem is differentiating spread of UC to the lung from a primary pulmonary SCC. Immunohistochemical analysis (IHC) for GATA binding protein 3 (GATA3), thrombomodulin (THROMBO), and uroplakin III was performed on a tissue microarray (TMA) containing 35 cases of invasive high-grade UC. GATA3 IHC was also performed on TMAs containing 38 high-grade (Gleason score ≥8) prostatic adenocarcinomas, representative tissue sections from 15 invasive anal SCCs, representative tissue sections from 19 invasive cervical SCCs, and TMAs with 12 invasive cervical carcinomas of the cervix [SCC (n=10), SCC with neuroendocrine features (n=1), and adenosquamous carcinoma (n=1)]. In addition, GATA3 IHC was performed on representative tissue sections from 15 pulmonary UC metastases and a TMA with 25 SCCs of the lung and 5 pulmonary non-small cell carcinomas with squamous features. GATA3, THROMBO, and uroplakin III were positive in 28 (80%), 22 (63%), and 21 (60%) cases of high-grade UC, respectively. All cases of GATA3-positive staining were nonfocal; 25 (89%) cases demonstrated moderate to strong staining, and 3 (11%) demonstrated weak staining. Of the 7 cases that failed to express GATA3, 5 were positive for THROMBO and/or uroplakin III, whereas 2 were negative for all 3 markers. None of the 38 high-grade prostatic adenocarcinomas was positive for GATA3. Weak GATA3 staining was present in occasional basal cells of benign prostate glands, in a few benign atrophic glands, and in urothelial metaplasia. Of the 15 cases of anal SCCs, 2 (7%) cases showed focal weak staining, and 1 (3%) showed focal moderate staining. Weak staining was also rarely

  19. Hyperbaric oxygen therapy for carcinoma of the cervix - Stages IIB, IIIA, IIIB, and IVA: results of a randomized study by the radiation therapy oncology group

    SciTech Connect

    Brady, L.W.; Plenk,H.P.; Hanley, J.A.

    1981-08-01

    A total of 65 patients with Stage IIB, IIIA, IIIB or IVA carcinoma of the cervix were randomized to receive conventional radiation therapy in air or hyperbaric oxygen therapy with radiation at optimal schedules. Seven patients could not be evaluated. Of the 19 patients treated in oxygen, 14 (73%) were living or had died without evidence of disease. Of the 29 patients treated with radiation alone 15 (52%) were alive or had died without evidence of tumor. Two of 29 patients treated in air and 5 of 19 patients treated in oxygen were dead of complications or intercurrent disease. No significant difference in survival could be demonstrated.

  20. Expression of survivin and matrix metalloproteinases in adenocarcinoma and squamous cell carcinoma of the uterine cervix.

    PubMed

    Yoshida, Hiroyuki; Sumi, Toshiyuki; Hyun, Yooji; Nakagawa, Eri; Hattori, Kanae; Yasui, Tomoyo; Morimura, Mina; Honda, Ken-Ichi; Nakatani, Tatsuya; Ishiko, Osamu

    2003-01-01

    Cervical cancer can be classified into two histological types: squamous cell carcinoma (SCA) and adenocarcinoma (ACA). Reportedly ACA has poorer prognoses, metastasizes more easily to lymph nodes, and is more resistant to radiotherapy than SCA. To clarify the cause of characteristic differences between these histological types, we examined the expressions of apoptosis inhibiting and tumor-invasion related factors in both histological types. We reviewed the 34 cases of cervical cancer (17 ACA, 17 SCA) that had surgery as their initial treatment at Osaka City University Medical School Hospital between 1996 and 2001. The differences of survivin, and matrix metalloproteinase (MMP-2, and MMP-7) expressions between both histological types were immunohistochemically assayed, and the correlation between the expression of each protein and clinicopathological characteristics was analyzed. Survivin was expressed significantly stronger in ACA cases (p=0.035). The number of patients who expressed MMP-2 and MMP-7 simultaneously was significantly higher in SCA cases (p=0.039). MMP-2 and MMP-7 had tendencies to be expressed stronger in SCA (p=0.057 and p=0.084, respectively). These results suggest that the differences of the expression of survivin (an apoptosis inhibiting factor), MMP-2, and MMP-7 (tumor-invasion related factors) between ACA and SCA were causes of the characteristic differences between the two histological types.

  1. Cervix carcinoma and incidental finding of medullary thyroid carcinoma by 18F-FDG PET/CT--clinical case.

    PubMed

    Chaushev, Borislav; Bochev, Pavel; Klisarova, Anelia; Yordanov, Kaloyan; Encheva, Elitsa; Dancheva, Jivka; Yordanova, Cvetelina; Hristozov, Kiril; Krasnaliev, Ivan; Radev, Radoslav; Nenkov, Rumen

    2014-01-01

    Thyroid nodules are encountered in clinical practice during the diagnostic procedures or patients' follow-up due to other diseases quite far from the thyroid gland with prevalence 4-50% in general population, depending on age, diagnostic method and race. The prevalence of thyroid nodules increases with age and their clarification should be done for their adequate treatment. An 18F-FDG PET/CT was done with a PET/CT scanner (Philips Gemini TF), consisting of dedicated lutetium orthosilicate full ring PET scanner and 16 slice CT. The PET/CT scan of the whole-body revealed on the CT portion a hypodense nodular lesion in the left lobe of the thyroid gland with increased uptake of 18F-FDG on the PET with SUVmax 10.3 and demonstrated a complete response to the induction therapy of the main oncological disease of the patient--squamous cell carcinoma. This clinical case demonstrates that whole-body 18F-FDG-PET/CT has an increasingly important role in the early evaluation of thyroid cancer as a second independent malignant localization. Focal thyroid lesion with high risk of thyroid malignancy was incidentally found on 18F-FDG PET/CT. PMID:25088110

  2. [Key enzymes of degradation and angiogenesis as a factors of tumor progression in squamous cell carcinoma of the cervix].

    PubMed

    Solov'eva, N I; Timoshenko, O S; Kugaevskaia, E V; Andreeva, Iu Iu; Zavalishina, L E

    2014-01-01

    A key role in tumor progression play two processes--the destruction and angiogenesis. Matrix metalloproteases (MMPs) play a leading role during tissue degradation. Tissue collagenase--MMP-1 and MT1-MMP hydrolyze fibrillar collagens, which are the basis of connective tissue matrix, and ensure the development of an invasive process. Gelatinase A and B (MMP-2 and MMP-9) hydrolyze collagen type IV, which is the basis of the basal membrane, and facilitate the development of metastasis. Endogenous tissue inhibitors TIMP-1 and TIMP-2 are involved in the regulation of MMP expression and activity. It has been established that MMP-9 release vascular endothelial growth factor (VEGF) associated with the STM--the primary inductor angiogenesis. Angiotensin-converting enzyme (ACE) participates in the induction of VEGF synthesis. ACE--a key enzyme of the renin-angiotensin system, forms angiotensin II, which interactes with the receptor ATIR and induces VEGF synthesis, as well as stimulates endothelial cell proliferation. Our experimental studies devoted to the study of particularity expression of key enzymes of destruction and angiogenesis in squamous cell carcinoma of the cervix (SCC). It was studied: MMP-1, MT1-MMP, MMP-2 and MMP-9 and their endogenous regulators: TIMP-1, TIMP-2, and as well as ACE. Work was performed on clinical specimens containing the tumor tissue, taking into account the presence or absence of metastasis to regional lymph nodes and the specimens of adjacent morphologically normal tissue. It was shown that the increase of MMP-1, MT1-MMP and MMP-9 expression and low of TIMP-1 and TIMP-2 expression makes the main contribution to the destructive (invasive) potential of SCC. The change of MMP-2 expression is not so significant and it is less influenced to the destructive potential. It was shown dramatic increasing of MMP-1 and MMP-9 activity in metastasizing tumor tissue ACE activity in a tumor in most of the samples was higher than the activity in normal tissues

  3. Insufficient cervix

    MedlinePlus

    ... the following problems are more likely to occur: Miscarriage in the 2nd trimester Labor begins too early, ... torn cervix from an earlier birth Having past miscarriages by the 4th month Having past late-term ...

  4. Radiotherapy and Hyperthermia for Treatment of Primary Locally Advanced Cervix Cancer: Results in 378 Patients

    SciTech Connect

    Franckena, Martine Lutgens, Ludy C.; Koper, Peter C.; Kleynen, Catharina E.; Steen-Banasik, Elsbieta M. van der; Jobsen, Jan J.; Leer, Jan Willem; Creutzberg, Carien L.; Dielwart, Michel F.; Norden, Yvette van; Canters, Richard A.M.; Rhoon, Gerard C. van; Zee, Jacoba van der

    2009-01-01

    Purpose: To report response rate, pelvic tumor control, survival, and late toxicity after treatment with combined radiotherapy and hyperthermia (RHT) for patients with locally advanced cervical carcinoma (LACC) and compare the results with other published series. Methods and Materials: From 1996 to 2005, a total of 378 patients with LACC (International Federation of Gynecology and Obstetrics Stage IB2-IVA) were treated with RHT. External beam radiotherapy (RT) was applied to 46-50.4 Gy and combined with brachytherapy. The hyperthermia (HT) was prescribed once weekly. Primary end points were complete response (CR) and local control. Secondary end points were overall survival, disease-specific survival, and late toxicity. Patient, tumor, and treatment characteristics predictive for the end points were identified in univariate and multivariate analyses. Results: Overall, a CR was achieved in 77% of patients. At 5 years, local control, disease-specific survival, and incidence of late toxicity Common Terminology Criteria for Adverse Events Grade 3 or higher were 53%, 47%, and 12%, respectively. In multivariate analysis, number of HT treatments emerged as a predictor of outcome in addition to commonly identified prognostic factors. Conclusions: The CR, local control, and survival rates are similar to previously observed results of RHT in the randomized Dutch Deep Hyperthermia Trial. Reported treatment results for currently applied combined treatment modalities (i.e., RT with chemotherapy and/or HT) do not permit definite conclusions about which combination is superior. The present results confirm previously shown beneficial effects from adding HT to RT and justify the application of RHT as first-line treatment in patients with LACC as an alternative to chemoradiation.

  5. Nonradioactive RNA in situ hybridization detection of human papillomavirus 16-E7 transcripts in squamous cell carcinomas of the uterine cervix using confocal laser scan microscopy.

    PubMed Central

    van den Brule, A. J.; Cromme, F. V.; Snijders, P. J.; Smit, L.; Oudejans, C. B.; Baak, J. P.; Meijer, C. J.; Walboomers, J. M.

    1991-01-01

    Paraffin-embedded squamous cell carcinomas of the uterine cervix selected for the presence of human papillomavirus (HPV) genotype 16 (n = 19) by polymerase chain reaction, were studied for transcription of the early open reading frame E7 (ORF E7). Nonradioactive RNA in situ hybridization (RISH) was performed using in vitro generated biotinylated probes. Hybrids were visualized by streptavidin gold and silver enhancement staining in combination with confocal laser scan microscopy. Quality of mRNA was verified by detection of beta-actin gene transcripts before E7 expression was studied. In all carcinomas containing HPV 16 DNA and showing beta-actin mRNA signals (n = 13), clear E7 ORF transcription could be found. Additional RNA-PCR on purified cytoplasmic RNA of snapfrozen tissue of identical carcinomas (n = 7) showed E6-E7 specific transcripts in all E7 RISH positive samples. These results indicate continuous expression of E7 ORF in all cervical carcinomas containing HPV 16 DNA and support an active role of the E7 ORF in the pathogenesis of cervical cancer. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:1719818

  6. The relationship between p16 expression and high-risk human papillomavirus infection in squamous cell carcinomas from sites other than uterine cervix: a study of 137 cases.

    PubMed

    Doxtader, Erika E; Katzenstein, Anna-Luise A

    2012-03-01

    p16 is known to be an excellent surrogate marker of human papillomavirus infection in squamous cell carcinoma of the cervix. Recent studies have demonstrated a link between human papillomavirus infection and a subset of head and neck squamous cell carcinomas, especially from the oropharynx. The aims of this study were to determine the incidence of p16 expression in squamous cell carcinomas of noncervical origin and to assess its utility as a surrogate marker of human papillomavirus infection in various noncervical primary sites. One hundred thirty-seven squamous cell carcinomas from 5 primary sites, including 34 from the oropharynx (tonsil and base of tongue), 43 cases from nonoropharyngeal head and neck sites, and 20 cases each from the lung, esophagus, and skin, were retrieved from our surgical pathology archives. Immunohistochemistry for p16 was performed on each case. All p16-positive cases and 21 p16-negative cases were further tested for both high-risk and low-risk human papillomavirus by in situ hybridization. p16 expression was detected in 54 cases overall, including 25 (74%) of 34 oropharyngeal squamous cell carcinomas, 8 (19%) of 43 nonoropharyngeal head and neck squamous cell carcinomas including 3 of 4 from the sinonasal cavity, 6 (30%) of 20 esophageal squamous cell carcinomas, 7 (35%) of 20 lung squamous cell carcinomas, and 8 (40%) of 20 skin squamous cell carcinomas. Of the 54 p16-positive cases, 30 were positive for high-risk human papillomavirus, including 24 (96%) of 25 from the oropharynx, 5 (63%) of 8 from nonoropharyngeal head and neck sites, and 1 (17%) of 6 from the esophagus. All 7 lung and 8 skin cases tested were negative. All p16-positive cases were negative for low-risk human papillomavirus. In selected head and neck squamous cell carcinomas, mainly from the oropharynx and sinonasal cavity, p16 positivity correlates well with high-risk human papillomavirus infection. p16 is not a reliable indicator of high-risk human papillomavirus

  7. Comparison of Southern blot analysis with isotopic and nonisotopic in situ hybridization for the detection of human papillomavirus sequences in invasive carcinoma of the uterine cervix.

    PubMed

    D'Amato, L; Pilotti, S; Rotola, A; Di Luca, D; Cassai, E; Rilke, F

    1992-03-01

    To compare the efficiency of hybridization methods for the detection of HPV genome, 22 cases of invasive squamous cell carcinoma of the uterine cervix were analyzed by Southern blot analysis and in situ hybridization carried out with 35S- and biotin-labeled probes. These cases contained from less than one to as many as 50 copies per cell of HPV 16 and 18 types. To increase the sensitivity of biotinylated probes, a silver enhancement procedure of the peroxidase reaction product was applied. Results showed that in situ hybridization performed with isotopic probes is as sensitive as Southern blot analysis and is more sensitive than that performed with biotin-labeled probe. However, the application of the silver enhancement procedure increases the percentage of HPV-positive cases from 27 to 50%.

  8. The prognostic value of histopathologic grading parameters and microvessel density in patients with early squamous cell carcinoma of the uterine cervix.

    PubMed

    Graflund, Marianne; Sorbe, B; Hussein, A; Bryne, M; Karlsson, M

    2002-01-01

    The purpose of this study was to investigate the prognostic importance of clinical and histopathologic factors, including malignancy grading systems (MGS), partial index (PI), invasive front grading (IFG), and microvessel density. A complete geographic series of 172 early stage (FIGO I-II) cervical carcinomas treated by Wertheim-Meigs surgery during the period 1965-1990 was studied. The patients were followed up for at least 10 years. Significant prognostic factors for disease-free survival were lymph node status (P < 0.0000001), radical surgical margins (P = 0.00003), and tumor size (P = 0.008). In a multivariate Cox analysis it was shown that lymph node status was the single most important prognostic factor with regard to disease-free survival. The total MGS and the PI scores were highly significantly (P = 0.0001) associated with pelvic lymph node metastases and disease-free survival rate in squamous cell carcinomas. The MGS and the PI systems were superior to the IFG system in predicting lymph node metastases. The total IFG score was also a statistically highly significant (P = 0.003) prognostic factor with regard to disease-free survival in both univariate and multivariate analyses. Microvessel density was a nonsignificant prognostic factor. There was a highly significant (P = 0.002) association between vascular space invasion of tumor cells and the presence of lymph node metastases. In conclusion, histopathologic malignancy grading systems provide valuable prognostic information in patients with early stage squamous cell carcinomas of the uterine cervix. PMID:11860534

  9. Advanced Treatment for Basal Cell Carcinomas

    PubMed Central

    Atwood, Scott X.; Whitson, Ramon J.; Oro, Anthony E.

    2014-01-01

    Basal cell carcinomas (BCCs) are very common epithelial cancers that depend on the Hedgehog pathway for tumor growth. Traditional therapies such as surgical excision are effective for most patients with sporadic BCC; however, better treatment options are needed for cosmetically sensitive or advanced and metastatic BCC. The first approved Hedgehog antagonist targeting the membrane receptor Smoothened, vismodegib, shows remarkable effectiveness on both syndromic and nonsyndromic BCCs. However, drug-resistant tumors frequently develop, illustrating the need for the development of next-generation Hedgehog antagonists targeting pathway components downstream from Smoothened. In this article, we will summarize available BCC treatment options and discuss the development of next-generation antagonists. PMID:24985127

  10. [Analysis of seven year prophylactic examinations of uterine cervix carcinoma in women living in the town of Kielce].

    PubMed

    Malarewicz, A; Rosiak, J

    1995-04-01

    The authors are presenting an analysis of the prophylactic examinations carried out within the period of seven years among women under the care of the Municipal Health Care Center in Kielce. They are also trying to evaluate the influence such examinations have in forming up the detectability of preneoplastic states and cancer of the uterine cervix. The studies were carried out from 1982-1988. A rule was adopted to repeat the examinations every two years. Owing to organizing difficulties, the first stage of the examinations took three years. The basis of the prophylactic examinations was cytologic examination. The detectability of intraepithelial neoplasm of the uterine cervix (CIN) in the three stages was 0.26%, 0.16%, and 0.07%. It was observed therefore, the gradual drop in the number of the detectable CIN among the population in the duration of the studies. A "shift" of detectable neoplasma changes in the uterine cervix in the direction of a higher percentage of preinvasive cancers and with an early invasion was observed. This shift, beside the stable decrement of the absolute number of detectable cancers is a favourable phenomenon and testifies the great usefulness and the effectiveness of the studies.

  11. Predictive markers in advanced renal cell carcinoma.

    PubMed

    Michaelson, M Dror; Stadler, Walter M

    2013-08-01

    Predictive markers of response to therapy are increasingly important in advanced renal cell carcinoma (RCC) due to the proliferation of treatment options in recent years. Different types of potential predictive markers may include clinical, toxicity-based, serum, tissue, and radiologic biomarkers. Clinical factors are commonly used in overall prognostic models of RCC but have limited utility in predicting response to therapy. Correlation between development of particular toxicities and response to therapy has been noted, such as the correlation between hypertension and response to angiogenesis-targeted therapy. Serum and tissue biomarkers will be covered in detail elsewhere, but factors such as serum lactate dehydrogenase (LDH) and circulating cytokines show promise in this regard. Finally, baseline or early treatment radiology studies may have predictive ability for longer term efficacy, with most studies to date focusing on functional imaging modalities such as positron emission tomography (PET) scans, dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI), and DCE ultrasound (US). The ultimate goal of developing predictive biomarkers is to enable rational and personalized treatment strategies for patients with advanced RCC. PMID:23972709

  12. [Cervix cancer].

    PubMed

    Pointreau, Y; Ruffier Loubière, A; Denis, F; Barillot, I

    2010-11-01

    Cervix cancers declined in most developed countries in recent years, but remain, the third worldwide leading cause of cancer death in women. A precise staging, based on clinical exam, an abdominal and pelvic MRI, a possible PET-CT and a possible lymph node sampling is necessary to adapt the best therapeutic strategy. In France, the treatments of tumors of less than 4 cm without nodal involvement are often based on radiotherapy followed by surgery and, whereas tumors larger than 4 cm and involved nodes are treated with concurrent chemoradiotherapy. Based on an illustrated clinical case, indications, delineation, dosimetry and complications expected with radiotherapy are demonstrated.

  13. New Strategies for Multimodality Therapy in Treating Locally Advanced Cervix Cancer.

    PubMed

    Verma, Jonathan; Monk, Bradley J; Wolfson, Aaron H

    2016-10-01

    Cervical cancer is the fourth most common cause of cancer of women worldwide. In the developing world, it comprises 12% of all cancers of women. Since 1999, the mainstay of treatment for locally advanced cervical cancer (LACC) has been concurrent cisplatin-based chemoradiation. However, outcomes in this disease remain suboptimal, with long-term progression-free survival and overall survival rates of approximately 60%. There are several new strategies of combined modality treatment under evaluation in LACC, including chemotherapy before and after treatment as well as novel agents such as poly-adenosine diphosphate ribose polymerase inhibitors, antiangiogenic blockage, and immunotherapy. We provide a brief overview of these strategies and their potential in the treatment of women with LACC. PMID:27619255

  14. The consistency of Fletcher-Suit applicator geometry and of the rectal probe’s position in high dose rate brachytherapy treatment fraction of cervix carcinoma

    PubMed Central

    2009-01-01

    Purpose The dose values computed with the treatment planning system and the in vivo dose measurements with semiconductor detectors in rectum during the high dose rate brachytherapy treatment fraction of the cervix carcinoma are occasionally significantly different. We’ve investigated the consistency of the Fletcher-Suit applicator geometry and the in vivo rectal probe’s position stability during the high dose rate brachytherapy treatment fraction. Material and methods The patient lied in a lithotomic position during a biplane reconstruction images, throughout the treatment planning and dose administration. We obtained post-treatment reconstruction images and prepared a post-treatment plan. The amount of 14 treatment fractions of 10 patients were considered in the study. Two methods were applied: evaluation of the difference of reconstructed pre-treatment and post-treatment applicator points and rectal probe’s detectors being relevant to the co-ordinate system fixed to the applicator, and estimation of applicators and rectal probe’s reallocation with respect to the pelvic bones with registration of pre- and post-treatment reconstruction images. Results We’ve experienced good consistency in the Fletcher-Suit applicator geometry in all treatment fractions. 70% of them presented small variation in the rectal probe’s position, while the rest showed significant shift in the applicator or rectal probe’s position with regard to the pelvic bones.

  15. [Cytological finding in the pre- and early stages of cervix carcinoma--a contribution to the evaluation of Papanicolau III].

    PubMed

    Bader, G; Büttner, H H; Neumann, H G; Rhode, E; Beust, M

    1977-01-01

    Cytologic findings and the histologic diagnosis are compared in 326 cervical cones. We have found following ratio of the groups Papanicolaou (Pap) III: Pap IV--in dysplasia 1: 1: 1, in "more dysplasia than carcinoma in situ (CIS)" 1:2:2. The Pap IV dominates in "pure" CIS and in cones with "more CIS than dysplasia". We take out of the Pap III ("with cytologic control") cases named "Pap III with necessity for histologic diagnosis". We have found in this subgroup of Pap III prestages or early stages of cervical carcinoma.

  16. Advances in systemic treatment for nasopharyngeal carcinoma.

    PubMed

    Tan, Wan-Ling; Tan, Eng-Huat; Lim, Darren Wan-Teck; Ng, Quan-Sing; Tan, Daniel Shao-Weng; Jain, Amit; Ang, Mei-Kim

    2016-04-01

    Nasopharyngeal carcinoma (NPC) is a unique disease endemic in Asia. It is etiologically linked to the Epstein-Barr virus and is both radio- and chemo-sensitive. While radiotherapy (RT) remains the primary treatment modality with high cure rates for early stage disease, systemic treatment forms an important integral component in the treatment of NPC, both in the non-metastatic as well as palliative setting. Presently, standard therapy in locally advanced NPC comprises conventional cytotoxic chemotherapy administered concurrently during RT. The role of induction chemotherapy and adjuvant chemotherapy remain to be well-defined. Further research strategies in non-metastatic disease will require better identification of patients with high risk disease, and determining the optimal sequence and combination of chemotherapeutic regimens. In metastatic disease, whilst chemotherapy remains the mainstay of care, resistance inevitably develops. Development of molecularly targeted therapies has not yielded much success to date, and further research has been focused on development of EBV-targeted strategies such as vaccination or administration of cytotoxic T-cells directed towards EBV, as well as evaluation of immune checkpoint inhibition approaches. PMID:27121881

  17. Advances in Management of Hepatocellular Carcinoma.

    PubMed

    Intaraprasong, Pongphob; Siramolpiwat, Sith; Vilaichone, Ratha-Korn

    2016-01-01

    Hepatocellular carcinoma (HCC) is the most frequent type of malignant liver tumor and a high impact health problem worldwide. The prevalence of HCC is particularly high in many Asian and African countries. Some HCC patients have no symptoms prior to diagnosis and many of them therefore present at late stage and have a grave prognosis. The well-established causes of HCC are chronic hepatitis B virus (HBV) or chronic hepatitis C virus (HCV) infection or alcoholic cirrhosis and nonalcoholic steatohepatitis. The Barcelona Clinic Liver Cancer (BCLC) Staging System remains the most widely used for HCC management guidelines. To date, the treatments for HCC are still very challenging for physicians due to limited resources in many parts of the world, but many options of management have been proposed, including hepatic resection, liver transplantation, ablative therapy, chemoembolization, sora nib and best supportive care. This review article describes the current evidence-based management of HCC with focus on early to advance stages that impact on patient overall survival. PMID:27644603

  18. Prognostic Value of Pretreatment Carcinoembryonic Antigen After Definitive Radiotherapy With or Without Concurrent Chemotherapy for Squamous Cell Carcinoma of the Uterine Cervix

    SciTech Connect

    Huang, Eng-Yen; Hsu, Hsuan-Chih; Sun, Li-Min; Chanchien, Chan-Chao; Lin, Hao; Chen, Hui-Chun; Tseng, Chih-Wen; Ou, Yu-Che; Chang, Hung-Yao; Fang, Fu-Min; Huang, Yu-Jie; Wang, Chang-Yu; Lu, Hsien-Ming; Tsai, Ching-Chou; and others

    2011-11-15

    Purpose: To evaluate whether pretreatment carcinoembryonic antigen (CEA) levels have a prognostic role in patients after definitive radiotherapy for squamous cell carcinoma (SCC) of the uterine cervix. Methods and Materials: A retrospective study of 550 patients was performed. The SCC antigen (SCC-Ag) and CEA levels were regarded as elevated when they were {>=}2 and {>=}5 ng/mL, respectively. A total of 208 patients underwent concurrent chemoradiotherapy (CCRT). The Kaplan-Meier method was used to calculate the distant metastasis (DM), local failure (LF), disease-free survival (DFS), and overall survival (OS) rates. Multivariate analysis was performed using the Cox proportional hazards model. The hazard ratio (HR) with 95% confidence interval (CI) was evaluated for the risk of a poor prognosis. Results: Compared with the patients with normal CEA/SCC-Ag levels, CEA levels {>=}10 ng/mL but without elevated SCC-Ag levels was an independent factor for LF (HR, 51.81; 95% CI, 11.51-233.23; p < .001), DM (HR, 6.04; 95% CI, 1.58-23.01; p = .008), DFS (HR, 10.17; 95% CI, 3.18-32.56; p < .001), and OS (HR, 5.75; 95% CI, 1.82-18.18; p = .003) after RT alone. However, no significant role for CEA was noted in patients with SCC-Ag levels {>=}2 ng/mL. In patients undergoing CCRT, a CEA level {>=}10 ng/mL was an independent factor for LF (HR, 2.50; 95% CI, 1.01-6.21; p = .047), DM (HR, 3.41; 95% CI, 1.56-7.46; p = .002), DFS (HR, 2.73; 95% CI, 1.39-5.36; p = .003), and OS (HR, 3.93; 95% CI 1.99-7.75; p < .001). A SCC-Ag level of {>=}40 ng/mL was another prognostic factor for DM, DFS, and OS in patients undergoing not only CCRT, but also RT alone. The 5-year OS rate for CCRT patients with CEA <10 ng/mL and {>=}10 ng/mL was 75.3% and 35.8%, respectively (p < .001). CCRT was an independent factor for better OS (HR, 0.69; 95% CI, 0.50-0.97; p = .034). Conclusion: Pretreatment CEA levels in patients with SCC of the uterine cervix provide complementary information for predicting LF, DM

  19. Treatment Outcome of Medium-Dose-Rate Intracavitary Brachytherapy for Carcinoma of the Uterine Cervix: Comparison With Low-Dose-Rate Intracavitary Brachytherapy

    SciTech Connect

    Kaneyasu, Yuko; Kita, Midori; Okawa, Tomohiko; Maebayashi, Katsuya; Kohno, Mari; Sonoda, Tatsuo; Hirabayashi, Hisae; Nagata, Yasushi; Mitsuhashi, Norio

    2012-09-01

    Purpose: To evaluate and compare the efficacy of medium-dose-rate (MDR) and low-dose-rate (LDR) intracavitary brachytherapy (ICBT) for uterine cervical cancer. Methods and Materials: We evaluated 419 patients with squamous cell carcinoma of the cervix who were treated by radical radiotherapy with curative intent at Tokyo Women's Medical University from 1969 to 1999. LDR was used from 1969 to 1986, and MDR has been used since July 1987. When compared with LDR, fraction dose was decreased and fraction size was increased (1 or 2 fractions) for MDR to make the total dose of MDR equal to that of LDR. In general, the patients received a total dose of 60 to 70 Gy at Point A with external beam radiotherapy combined with brachytherapy according to the International Federation of Gynecology and Obstetrics stage. In the LDR group, 32 patients had Stage I disease, 81 had Stage II, 182 had Stage III, and 29 had Stage IVA; in the MDR group, 9 patients had Stage I disease, 19 had Stage II, 55 had Stage III, and 12 had Stage IVA. Results: The 5-year overall survival rates for Stages I, II, III, and IVA in the LDR group were 78%, 72%, 55%, and 34%, respectively. In the MDR group, the 5-year overall survival rates were 100%, 68%, 52%, and 42%, respectively. No significant statistical differences were seen between the two groups. The actuarial rates of late complications Grade 2 or greater at 5 years for the rectum, bladder, and small intestine in the LDR group were 11.1%, 5.8%, and 2.0%, respectively. The rates for the MDR group were 11.7%, 4.2%, and 2.6%, respectively, all of which were without statistical differences. Conclusion: These data suggest that MDR ICBT is effective, useful, and equally as good as LDR ICBT in daytime (about 5 hours) treatments of patients with cervical cancer.

  20. Multifocal FIGO Stage IA1 Squamous Carcinoma of the Cervix: Criteria for Identification, Staging, and its Good Clinical Outcome.

    PubMed

    Day, Elizabeth; Duffy, Siobhan; Bryson, Gareth; Syed, Sheeba; Shanbhag, Smruta; Burton, Kevin; Lindsay, Rhona; Siddiqui, Nadeem; Millan, David

    2016-09-01

    Multifocal squamous cervical carcinomas account for up to 25% of IA1 tumors identified on excisional biopsy, yet there are no uniformly accepted histopathologic criteria for defining and staging these lesions. Here, we use a strict case definition and meticulous specimen processing from colposcopist to pathologist to identify and follow-up 25 cases of multifocal IA1 cervical squamous carcinomas identified in excisional biopsies. We stage these tumors using the dimensions of the largest focus and a minimum of 2 mm between each foci to define multifocality. The cases are followed up for a median of 7 yr with no episodes of tumor recurrence or metastasis. We also show that the prevalence of residual preinvasive (20%) and invasive disease (5%) on repeat excision/surgery are comparable to data available for unifocal IA1 cases. Our study supports the hypothesis that multifocal lesions should be staged according to largest individual focus of invasion and we emphasize the importance of meticulous specimen handling to appropriately identify multifocal tumors. In addition, our analysis suggests that outcomes are comparable to unifocal lesions and supports the hypothesis that they may be managed in a similar manner. PMID:26863478

  1. Joint effects of different human papillomaviruses and Chlamydia trachomatis infections on risk of squamous cell carcinoma of the cervix uteri.

    PubMed

    Luostarinen, T; Lehtinen, M; Bjørge, T; Abeler, V; Hakama, M; Hallmans, G; Jellum, E; Koskela, P; Lenner, P; Lie, A K; Paavonen, J; Pukkala, E; Saikku, P; Sigstad, E; Thoresen, S; Youngman, L D; Dillner, J; Hakulinen, T

    2004-05-01

    This case-control study based in Nordic serum banks evaluated the joint effects of infections with genital human papillomavirus (HPV) types, and Chlamydia trachomatis in the aetiology of cervical squamous cell carcinoma. Through a linkage with the cancer registries, 144 cases were identified and 420 controls matched to them. Exposure to past infections was defined by the presence of specific IgG antibodies. The odds ratio (OR) for the second-order interaction of HPV16, HPV6/11 and C. trachomatis was small (1.0) compared to the expected multiplicative OR, 57, and the additive OR, 11. The interactions were not materially different among HPV16 DNA-positive squamous cell carcinomas. When HPV16 was replaced with HPV18/33 in the analysis of second-order interactions with HPV6/11 and C. trachomatis, there was no evidence of interaction, the joint effect being close to the expected additive OR. Possible explanations for the observed antagonism include misclassification, selection bias or a true biological phenomenon with HPV6/11 and C. trachomatis exposures antagonizing the carcinogenic effects of HPV16.

  2. Phase III trial comparing two low dose rates in brachytherapy of cervix carcinoma: Report at two years

    SciTech Connect

    Lambin, P.; Gerbaulet, A.; Kramer, A.; Haie-Meder, C.; Malaise, E.P.; Chassagne, D. ); Scalliet, P. )

    1993-02-15

    This Phase III randomized trial examined the effect of two low dose rates (0.73 or 0.38 Gy[center dot]h[sup [minus]1]) on the local control, survival, relapse-free survival, complications, and secondary effects in the treatment of cervical cancers. A total of 204 Stage Ib or II cervical carcinoma patients were included between January 1985 and September 1988. Treatment consisted of uterovaginal [sup 137]Cs irradiation followed by surgery. The two groups were similar for age, tumor stage and medical or surgical history. Their brachytherapy parameters were also similar (60 Gy pear dimensions, dose to critical organs, total kerma, etc....). There were no differences in the short-term effects or therapeutic outcome. However, overall complications and side effects observed after 6 months were significantly more frequent (p < 0.01) in the higher dose rate group. 40 refs., 4 figs., 6 tabs.

  3. Evaluation and comparison of histopathologic grading systems of epithelial carcinoma of the uterine cervix: Gynecologic Oncology Group studies.

    PubMed

    Stock, R J; Zaino, R; Bundy, B N; Askin, F B; Woodward, J; Fetter, B; Paulson, J A; DiSaia, P J; Stehman, F B

    1994-04-01

    The subjects of this study are 445 patients with advanced cervical cancer treated by standardized radiation therapy. Upon entry into one of two Gynecologic Oncology Group (GOG) protocols, original pathologic diagnoses and histologic tumor descriptions for each patient were compared with separate evaluations made by a consensus opinion of two GOG pathologists. A review diagnosis using grade, cell type, and the Stendahl scoring system was then made by the first author (R.J.S.) without knowledge of the prior diagnoses. Of the original pathologists' diagnoses, 21% did not include grade or cell type. There was little agreement among the different pathologists as to the use of either specific grade or cell type. Histologic grade, irrespective of the pathologists making the diagnosis, had no correlation to prognosis. The Reagan and Wentz large-cell keratinizing (LCK) cell type, when applied by the author to tumors with any form of squamous keratinization present, identified a group of patients with a poorer prognosis, although not independently of other prognostic factors. The Stendahl scoring system identified a number of patients with both a poorer and better prognosis. This was statistically significant and independent of other risk factors. A major limitation, however, was the number of patients evaluable because of inadequate biopsy material in 23.6% of the study group.

  4. Molecular pathogenesis of hepatocellular carcinoma and impact of therapeutic advances

    PubMed Central

    Dhanasekaran, Renumathy; Bandoh, Salome; Roberts, Lewis R.

    2016-01-01

    Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality and has an increasing incidence worldwide. HCC can be induced by multiple etiologies, is influenced by many risk factors, and has a complex pathogenesis. Furthermore, HCCs exhibit substantial heterogeneity, which compounds the difficulties in developing effective therapies against this highly lethal cancer. With advances in cancer biology and molecular and genetic profiling, a number of different mechanisms involved in the development and progression of HCC have been identified. Despite the advances in this area, the molecular pathogenesis of hepatocellular carcinoma is still not completely understood. This review aims to elaborate our current understanding of the most relevant genetic alterations and molecular pathways involved in the development and progression of HCC, and anticipate the potential impact of future advances on therapeutic drug development. PMID:27239288

  5. Liver transplantation for advanced hepatocellular carcinoma

    PubMed Central

    Lee, Hae Won; Suh, Kyung-Suk

    2016-01-01

    There has been ongoing debate that the Milan criteria may be too strict that a significant number of patients who could benefit from liver transplantation (LT) might have been excluded. Based on this idea, various studies have been conducted to further expand the Milan criteria and give more HCC patients a chance of cure. In deceased donor LT (DDLT) setting, expansion of the criteria is relatively tempered because the results of LT for HCC should be comparable to those of patients with non-malignant indications. On the other hand, in living donor LT (LDLT) situation, liver grafts are not public resources. The acceptable target outcomes for LDLT might be much lower than those for DDLT. Patients with biologically favorable tumors might have excellent survivals after LT despite morphological advanced HCCs. Therefore, the significance and utility of biological tumor parameters for selecting suitable LT candidates have been increased to predict HCC recurrence after LT. Although there is no consensus regarding the use of prognostic biomarkers in LT selection criteria for HCC, the combination of conventional morphological parameters and new promising biomarkers could help us refine and expand the LT criteria for HCC in the near future. PMID:27729631

  6. Progress in systemic therapy of advanced hepatocellular carcinoma

    PubMed Central

    Gong, Xin-Lei; Qin, Shu-Kui

    2016-01-01

    Primary liver cancer, mainly consisting of hepatocellular carcinoma (HCC), is one of common malignancies worldwide, and prevalent among the Chinese population. A diagnosis of early stage HCC has proven to be very difficult because of its insidious feature in onset and development. At the time of diagnosis, most HCC cases are locally advanced and/or distant metastatic, which results in difficulty to be treated and poor prognosis. For advanced HCC, systemic therapy is frequently adopted as an important palliative method. In recent years, clinical studies and observations have often reported about systemic anti-cancer therapy of advanced HCC, including molecular target therapy, systemic chemotherapy and immunotherapy. In this article, we review these treatment modalities to provide a reference for clinicians. PMID:27547002

  7. Conventional chemotherapy and emerging targeted therapy for advanced adrenocortical carcinoma.

    PubMed

    Xu, Yun-Ze; Zhu, Yu

    2013-02-01

    Adrenocortical carcinoma (ACC) is a rare but typically aggressive malignancy. Radical surgery remains the potentially curative option. However, about one third of patients initially present with distant metastases. Regarding to chemotherapy, mitotane alone or in combination with cytotoxic drugs should be the first selection. Meanwhile, a phase lll clinical trial of etoposide, doxorubicin, cisplatin plus mitotane or streptozotocin plus mitotane is currently undergoing worldwide. The study on molecular pathogenesis of ACC is progressing. A lot of targeted therapies are also enrolled in preclinical investigations and clinical trials, including small-molecule tyrosine kinase inhibitors, antiangiogenic compounds. This article introduced the conventional chemotherapy, newly developed targeted therapy for advanced ACC.

  8. Regulation of matrix metalloproteinase-9 transcription in squamous cell carcinoma of uterine cervix: the role of human papillomavirus gene E2 expression and activation of transcription factor NF-kappaB.

    PubMed

    Gasparian, A V; Fedorova, M D; Kisselev, F L

    2007-08-01

    Matrix metalloproteinase-9 (MMP-9) plays an important role in initiation and progression of squamous cell carcinoma (SCC) of human uterine cervix. Regulation of MMP-9 expression in such tumors is insufficiently studied. Involvement of the human papillomavirus (HPV) gene E2 and transcription factor NF-kappaB in the regulation of MMP-9 transcription has been shown in some model systems and types of malignant tumors. The present work was mainly designed to reveal a possible role of the HPV gene E2 and transcription factor NF-kappaB in the induction of MMP-9 expression in SCC. Specimens of tumor and corresponding adjacent normal tissue from 26 patients with SCC of the uterine cervix were studied. The intact E2 frame was observed in 19 of 26 (73.1%), the E2 gene mRNA was expressed in 10 of 15 (66.7%), NF-kappaB was activated in 17 of 23 (73.9%), and the expression of MMP-9 mRNA was recorded in 10 of 20 (50%) of the informative cases. The MMP-9 transcription did not correlate with gene E2 status, but in all cases correlated with the activation of NF-kappaB transcription factor (10 of 10 vs. 5 of 10 MMP-9-negative cases, p = 0.016). Thus, the NF-kappaB role has been proved in the regulation of MMP-9 transcription in SCC. There was no correlation of the E2 status and MMP-9 expression with clinical/morphological characteristics of the tumors: size, local invasiveness, metastasizing into regional lymph nodes, and level of differentiation. The high intensity of NF-kappaB activation correlated with low degree of differentiation of the tumors studied (p = 0.044). These findings suggested that NF-kappaB should be a molecular factor of the poor prognosis of human SCC.

  9. Recent Advances in Tumor Ablation for Hepatocellular Carcinoma.

    PubMed

    Kang, Tae Wook; Rhim, Hyunchul

    2015-09-01

    Image-guided tumor ablation for early stage hepatocellular carcinoma (HCC) is an accepted non-surgical treatment that provides excellent local tumor control and favorable survival benefit. This review summarizes the recent advances in tumor ablation for HCC. Diagnostic imaging and molecular biology of HCC has recently undergone marked improvements. Second-generation ultrasonography (US) contrast agents, new computed tomography (CT) techniques, and liver-specific contrast agents for magnetic resonance imaging (MRI) have enabled the early detection of smaller and inconspicuous HCC lesions. Various imaging-guidance tools that incorporate imaging-fusion between real-time US and CT/MRI, that are now common for percutaneous tumor ablation, have increased operator confidence in the accurate targeting of technically difficult tumors. In addition to radiofrequency ablation (RFA), various therapeutic modalities including microwave ablation, irreversible electroporation, and high-intensity focused ultrasound ablation have attracted attention as alternative energy sources for effective locoregional treatment of HCC. In addition, combined treatment with RFA and chemoembolization or molecular agents may be able to overcome the limitation of advanced or large tumors. Finally, understanding of the biological mechanisms and advances in therapy associated with tumor ablation will be important for successful tumor control. All these advances in tumor ablation for HCC will result in significant improvement in the prognosis of HCC patients. In this review, we primarily focus on recent advances in molecular tumor biology, diagnosis, imaging-guidance tools, and therapeutic modalities, and refer to the current status and future perspectives for tumor ablation for HCC.

  10. Technical advances in external radiotherapy for hepatocellular carcinoma

    PubMed Central

    Park, Shin-Hyung; Kim, Jae-Chul; Kang, Min Kyu

    2016-01-01

    Radiotherapy techniques have substantially improved in the last two decades. After the introduction of 3-dimensional conformal radiotherapy, radiotherapy has been increasingly used for the treatment of hepatocellular carcinoma (HCC). Currently, more advanced techniques, including intensity-modulated radiotherapy (IMRT), stereotactic ablative body radiotherapy (SABR), and charged particle therapy, are used for the treatment of HCC. IMRT can escalate the tumor dose while sparing the normal tissue even though the tumor is large or located near critical organs. SABR can deliver a very high radiation dose to small HCCs in a few fractions, leading to high local control rates of 84%-100%. Various advanced imaging modalities are used for radiotherapy planning and delivery to improve the precision of radiotherapy. These advanced techniques enable the delivery of high dose radiotherapy for early to advanced HCCs without increasing the radiation-induced toxicities. However, as there have been no effective tools for the prediction of the response to radiotherapy or recurrences within or outside the radiation field, future studies should focus on selecting the patients who will benefit from radiotherapy. PMID:27621577

  11. Technical advances in external radiotherapy for hepatocellular carcinoma

    PubMed Central

    Park, Shin-Hyung; Kim, Jae-Chul; Kang, Min Kyu

    2016-01-01

    Radiotherapy techniques have substantially improved in the last two decades. After the introduction of 3-dimensional conformal radiotherapy, radiotherapy has been increasingly used for the treatment of hepatocellular carcinoma (HCC). Currently, more advanced techniques, including intensity-modulated radiotherapy (IMRT), stereotactic ablative body radiotherapy (SABR), and charged particle therapy, are used for the treatment of HCC. IMRT can escalate the tumor dose while sparing the normal tissue even though the tumor is large or located near critical organs. SABR can deliver a very high radiation dose to small HCCs in a few fractions, leading to high local control rates of 84%-100%. Various advanced imaging modalities are used for radiotherapy planning and delivery to improve the precision of radiotherapy. These advanced techniques enable the delivery of high dose radiotherapy for early to advanced HCCs without increasing the radiation-induced toxicities. However, as there have been no effective tools for the prediction of the response to radiotherapy or recurrences within or outside the radiation field, future studies should focus on selecting the patients who will benefit from radiotherapy.

  12. Technical advances in external radiotherapy for hepatocellular carcinoma.

    PubMed

    Park, Shin-Hyung; Kim, Jae-Chul; Kang, Min Kyu

    2016-08-28

    Radiotherapy techniques have substantially improved in the last two decades. After the introduction of 3-dimensional conformal radiotherapy, radiotherapy has been increasingly used for the treatment of hepatocellular carcinoma (HCC). Currently, more advanced techniques, including intensity-modulated radiotherapy (IMRT), stereotactic ablative body radiotherapy (SABR), and charged particle therapy, are used for the treatment of HCC. IMRT can escalate the tumor dose while sparing the normal tissue even though the tumor is large or located near critical organs. SABR can deliver a very high radiation dose to small HCCs in a few fractions, leading to high local control rates of 84%-100%. Various advanced imaging modalities are used for radiotherapy planning and delivery to improve the precision of radiotherapy. These advanced techniques enable the delivery of high dose radiotherapy for early to advanced HCCs without increasing the radiation-induced toxicities. However, as there have been no effective tools for the prediction of the response to radiotherapy or recurrences within or outside the radiation field, future studies should focus on selecting the patients who will benefit from radiotherapy. PMID:27621577

  13. Transcatheter embolization of advanced renal cell carcinoma with radioactive seeds

    SciTech Connect

    Lang, E.K.; deKernion, J.B.

    1981-11-01

    Advanced renal cell carcinoma was treated by transcatheter embolization with radioactive seeds. There were 14 patients with nonresectable or metastatic disease (stage IV) and 8 with stage II tumors treated. In 8 patients the tumor was implanted with radon seeds, complemented by 2,500 rad of external beam therapy, and 10 were treated by embolization with 125iodine seeds. The total dose delivered ranged form 1,600 to 14,000 rad. Several patients also had intra-arterial chemotherapy. Survival was improved over previously reported studies: 13 of 22 (59 per cent) at risk for 2 years and 5 of 15 (33 per cent) for 5 years. Distant metastases did not resolve but significant local palliation was achieved. Tumor size decreased in all patients, 8 of whom subsequently underwent nephrectomy. Other local effects included pain control (10 per cent), weight gain (75 per cent) and control of hemorrhage (88 per cent). Toxicity was minimal and consisted of mild nausea or pain. This approach, using a low energy emitter, allows selective high dose radiation of the tumor, while sparing the adjacent normal tissues. In contrast to renal artery occlusion with inert embolic material, subsequent nephrectomy in patients with disseminated disease is not necessary. Transcatheter embolization with radioactive seeds should be considered a reasonable palliative procedure in patients with nonresectable primary renal cell carcinoma.

  14. Gross Hematuria and Bladder Tumor in a Patient with Advanced Thyroid Papillary Carcinoma

    PubMed Central

    Matsuo, Yuki; Ikeoka, Toshiyuki; Oba, Kojiro; Miyata, Yasuyoshi; Sakai, Hideki; Abe, Kuniko; Kawakami, Atsushi

    2013-01-01

    We present a 73-year-old female with advanced thyroid papillary carcinoma who complained of gross hematuria. We found a bladder tumor and considered it the cause of her symptom. Cystoscopic findings of the tumor were unusual, with peri-tumor vessel formation. Pathological examination of the bladder tumor was consistent with metastasis of thyroid papillary carcinoma. Therefore, we identified thyroid carcinoma metastasis to the urinary bladder as the cause of hematuria in our patient. Thyroid carcinoma metastasis to the bladder is extremely rare, but it should be included among differential diagnoses for gross hematuria in patients with a clinical history of thyroid carcinoma. PMID:23762664

  15. Advances in the management of basal cell carcinoma

    PubMed Central

    Carucci, John A.

    2015-01-01

    Basal cell carcinoma (BCC), a malignant neoplasm derived from non-keratinizing cells that originate in the basal layer of the epidermis, is the most common cancer in humans. Several factors such as anatomic location, histologic features, primary or recurrent tumors, and patient characteristics influence the choice of treatment modality for BCC. Mohs micrographic surgery (MMS) facilitates optimal margin control and conservation of normal tissue for the management of BCC; however, other treatment modalities may also be implemented in the correct clinical scenario. Other treatment modalities that will be reviewed include simple excision, electrodesiccation and curettage, cryotherapy, topical immunotherapy and chemotherapy, photodynamic therapy, and radiation therapy. In addition, targeted molecular therapeutic options for the treatment of advanced or metastatic BCC will be discussed in this informal review based on recent literature obtained by using PubMed with relevant search terms. PMID:26097726

  16. Recent Advances in Tumor Ablation for Hepatocellular Carcinoma.

    PubMed

    Kang, Tae Wook; Rhim, Hyunchul

    2015-09-01

    Image-guided tumor ablation for early stage hepatocellular carcinoma (HCC) is an accepted non-surgical treatment that provides excellent local tumor control and favorable survival benefit. This review summarizes the recent advances in tumor ablation for HCC. Diagnostic imaging and molecular biology of HCC has recently undergone marked improvements. Second-generation ultrasonography (US) contrast agents, new computed tomography (CT) techniques, and liver-specific contrast agents for magnetic resonance imaging (MRI) have enabled the early detection of smaller and inconspicuous HCC lesions. Various imaging-guidance tools that incorporate imaging-fusion between real-time US and CT/MRI, that are now common for percutaneous tumor ablation, have increased operator confidence in the accurate targeting of technically difficult tumors. In addition to radiofrequency ablation (RFA), various therapeutic modalities including microwave ablation, irreversible electroporation, and high-intensity focused ultrasound ablation have attracted attention as alternative energy sources for effective locoregional treatment of HCC. In addition, combined treatment with RFA and chemoembolization or molecular agents may be able to overcome the limitation of advanced or large tumors. Finally, understanding of the biological mechanisms and advances in therapy associated with tumor ablation will be important for successful tumor control. All these advances in tumor ablation for HCC will result in significant improvement in the prognosis of HCC patients. In this review, we primarily focus on recent advances in molecular tumor biology, diagnosis, imaging-guidance tools, and therapeutic modalities, and refer to the current status and future perspectives for tumor ablation for HCC. PMID:26674766

  17. Treatment of primary adenocarcinoma of the cervix.

    PubMed

    Weiner, S; Wizenberg, M J

    1975-06-01

    Between 1956 and 1971, a total of 74 cases of adenocarcinoma of the cervix was treatedin the Division of Radiation Therapy of the University of Maryland Hospital. Radical radiation therapy was followed by routine surgery early in the study;after 1967, surgery was used only for radiation failure. The likelihood of local control and 5-year survival was not improved by the routine addition of surgery to radical radiation, although the incidence of serious complications was markedly elevated. The results of treatment of adenocarcinoma of the cervix by radiation therapy alone are not significantly different from those achieved with squamous cell carcinoma. Surgery should be used as a salvage procedure in case of failure, rather than on a routine basis. PMID:1148986

  18. RGDS- and TAT-Conjugated Upconversion of NaYF4:Yb(3+)/Er(3+)&SiO2 Nanoparticles: In Vitro Human Epithelioid Cervix Carcinoma Cellular Uptake, Imaging, and Targeting.

    PubMed

    Kostiv, Uliana; Kotelnikov, Ilya; Proks, Vladimír; Šlouf, Miroslav; Kučka, Jan; Engstová, Hana; Ježek, Petr; Horák, Daniel

    2016-08-10

    Starting NaYF4:Yb(3+)/Er(3+) nanoparticles with size tuned from 24 to 33 nm were prepared by high-temperature coprecipitation of lanthanide chlorides in high-boiling organic solvents. To enhance colloidal stability in aqueous medium, an aminosilica shell was introduced on the surface by hydrolysis and condensation of tetramethyl orthosilicate and (3-aminopropyl)trimethoxysilane using a reverse microemulsion technique; to form alkyne groups, reaction with 4-pentynoic acid followed. Finally, the cell adhesive and cell penetrating azidopentanoyl-GGGRGDSGGGY-NH2 (RGDS) and azidopentanoyl-GGGRKKRRQRRR-NH2 (TAT) peptides were conjugated to the upconversion particles via Cu(I)-catalyzed alkyne-azide cycloaddition. The concentrations of the peptides bound to the nanoparticle surfaces and amount of adsorbed residual Cu(I) catalyst were determined using an (125)I-radiolabeled RGDS peptide and a (64)Cu(I)-doped catalyst, respectively. Targeting and uptake of the RGDS- and TAT-conjugated NaYF4:Yb(3+)/Er(3+)&SiO2 nanoparticles by human cervix carcinoma HeLa cells were monitored by confocal microscopy. RGDS-conjugated nanoparticle probes were mainly localized on the cell plasma membrane due to specific binding of the peptide to the corresponding integrins. In contrast, the TAT-conjugated nanoparticles were able to cross the cell membrane and accumulate in the cell cytoplasm. Thus, this new peptide bioconjugation approach supported both extra- and intracellular nanoparticle uptake, enabling targeting and imaging of the specific tumor phenotypes. PMID:27428386

  19. Hepatocellular carcinoma: Advances in diagnosis, management, and long term outcome

    PubMed Central

    Bodzin, Adam S; Busuttil, Ronald W

    2015-01-01

    Hepatocellular carcinoma (HCC) remains a common and lethal malignancy worldwide and arises in the setting of a host of diseases. The incidence continues to increase despite multiple vaccines and therapies for viruses such as the hepatitis B and C viruses. In addition, due to the growing incidence of obesity in Western society, there is anticipation that there will be a growing population with HCC due to non-alcoholic fatty liver disease. Due to the growing frequency of this disease, screening is recommended using ultrasound with further imaging using magnetic resonance imaging and multi-detector computed tomography used for further characterization of masses. Great advances have been made to help with the early diagnosis of small lesions leading to potential curative resection or transplantation. Resection and transplantation maybe used in a variety of patients that are carefully selected based on underlying liver disease. Using certain guidelines and clinical acumen patients may have good outcomes with either resection or transplantation however many patients are inoperable at time of presentation. Fortunately, the use of new locoregional therapies has made down staging patients a potential option making them potential surgical candidates. Despite a growing population with HCC, new advances in viral therapies, chemotherapeutics, and an expanding population of surgical and transplant candidates might all contribute to improved long-term survival of these patients. PMID:26019732

  20. A rare case of extensive skeletal muscle metastases in adenocarcinoma cervix identified by 18F-fluorodeoxyglucose positron emission tomography/computed tomography scan

    PubMed Central

    Vishnoi, Madan Gopal; Jain, Anurag; John, Arun Ravi; Paliwal, Dharmesh

    2016-01-01

    Adenocarcinoma cervix is an uncommon histological subtype of carcinoma cervix; further incidence of skeletal muscle metastases is even rarer. We report the identification of extensive fluorodeoxyglucose (FDG) avid metastatic skeletal muscle deposits in a known case of adenocarcinoma cervix. The largest lesion representative of muscle deposit in the right deltoid was histopathologically confirmed to be metastatic poorly differentiated carcinoma. This report also serves to highlight the importance of 18F-FDG positron emission tomography/computed tomography (CT) as compared to conventional imaging modalities such as CT and ultrasonography and comments better over the description of invasiveness as well as the extent of disease in carcinoma cervix. PMID:27385895

  1. BRAF Mutation Is Rare in Advanced-Stage Low-Grade Ovarian Serous Carcinomas

    PubMed Central

    Wong, Kwong-Kwok; Tsang, Yvonne T.M.; Deavers, Michael T.; Mok, Samuel C.; Zu, Zhifei; Sun, Charlotte; Malpica, Anais; Wolf, Judith K.; Lu, Karen H.; Gershenson, David M.

    2010-01-01

    Low-grade ovarian serous carcinomas are believed to arise via an adenoma-serous borderline tumor-serous carcinoma sequence. In this study, we found that advanced-stage, low-grade ovarian serous carcinomas both with and without adjacent serous borderline tumor shared similar regions of loss of heterozygosity. We then analyzed 91 ovarian tumor samples for mutations in TP53, BRAF, and KRAS. TP53 mutations were not detected in any serous borderline tumors (n = 30) or low-grade serous carcinomas (n = 43) but were found in 73% of high-grade serous carcinomas (n = 18). BRAF (n = 9) or KRAS (n = 5) mutation was detected in 47% of serous borderline tumors, but among the low-grade serous carcinomas (39 stage III, 2 stage II, and 2 stage I), only one (2%) had a BRAF mutation and eight (19%) had a KRAS mutation. The low frequency of BRAF mutations in advanced-stage, low-grade serous carcinomas, which contrasts with previous findings, suggests that aggressive, low-grade serous carcinomas are more likely derived from serous borderline tumors without BRAF mutation. In addition, advanced-stage, low-grade carcinoma patients with BRAF or KRAS mutation have a better apparent clinical outcome. However, further investigation is needed. PMID:20802181

  2. Long-Term Improvement in Treatment Outcome After Radiotherapy and Hyperthermia in Locoregionally Advanced Cervix Cancer: An Update of the Dutch Deep Hyperthermia Trial

    SciTech Connect

    Franckena, Martine Stalpers, Lukas J.A.; Koper, Peter C.M.; Wiggenraad, Ruud G.J.; Hoogenraad, Wim J.; Dijk, Jan D.P. van; Warlam-Rodenhuis, Carla C.; Jobsen, Jan J.; Rhoon, Gerard C. van; Zee, Jacoba van der

    2008-03-15

    Purpose: The local failure rate in patients with locoregionally advanced cervical cancer is 41-72% after radiotherapy (RT) alone, whereas local control is a prerequisite for cure. The Dutch Deep Hyperthermia Trial showed that combining RT with hyperthermia (HT) improved 3-year local control rates of 41-61%, as we reported earlier. In this study, we evaluate long-term results of the Dutch Deep Hyperthermia Trial after 12 years of follow-up. Methods and Materials: From 1990 to 1996, a total of 114 women with locoregionally advanced cervical carcinoma were randomly assigned to RT or RT + HT. The RT was applied to a median total dose of 68 Gy. The HT was given once weekly. The primary end point was local control. Secondary end points were overall survival and late toxicity. Results: At the 12-year follow-up, local control remained better in the RT + HT group (37% vs. 56%; p = 0.01). Survival was persistently better after 12 years: 20% (RT) and 37% (RT + HT; p = 0.03). World Health Organization (WHO) performance status was a significant prognostic factor for local control. The WHO performance status, International Federation of Gynaecology and Obstetrics (FIGO) stage, and tumor diameter were significant for survival. The benefit of HT remained significant after correction for these factors. European Organization for Research and Treatment of Cancer Grade 3 or higher radiation-induced late toxicities were similar in both groups. Conclusions: For locoregionally advanced cervical cancer, the addition of HT to RT resulted in long-term major improvement in local control and survival without increasing late toxicity. This combined treatment should be considered for patients who are unfit to receive chemotherapy. For other patients, the optimal treatment strategy is the subject of ongoing research.

  3. Preoperative Concurrent Radiation Therapy and Chemotherapy for Bulky Stage IB2, IIA, and IIB Carcinoma of the Uterine Cervix With Proximal Parametrial Invasion

    SciTech Connect

    Huguet, Florence; Cojocariu, Oana-Maria; Levy, Pierre; Lefranc, Jean-Pierre; Darai, Emile; Jannet, Denis; Ansquer, Yan; Lhuillier, Pierre-Eugene; Benifla, Jean-Louis; Seince, Nathalie; Touboul, Emmanuel

    2008-12-01

    Purpose: To evaluate toxicity, local tumor control, and survival after preoperative chemoradiation for operable bulky cervical carcinoma. Methods and Materials: Between December 1991 and July 2006, 92 patients with operable bulky stage IB2, IIA, and IIB cervical carcinoma without pelvic or para-aortic nodes on pretreatment imaging were treated. Treatment consisted of preoperative external beam pelvic radiation therapy (EBRT) and concomitant chemotherapy (CT) during the first and fourth weeks of radiation combining 5-fluorouracil and cisplatin. The pelvic radiation dose was 40.5 Gy over 4.5 weeks. EBRT was followed by low-dose rate uterovaginal brachytherapy with a total dose of 20 Gy in 62 patients. After a median rest period of 44 days, all patients underwent Class II modified radical hysterectomy with bilateral pelvic lymphadenectomy. Thirty patients who had not received preoperative uterovaginal brachytherapy underwent postoperative low-dose-rate vaginal brachytherapy at a dose of 20 Gy. The mean follow-up was 46 months. Results: Pathologic residual tumor was observed in 43 patients. After multivariate analysis, additional preoperative uterovaginal brachytherapy was the single significant predictive factor for pathologic complete response rate (p = 0.019). The 2- and 5-year disease-free survival (DFS) rates were 80.4% and 72.2%, respectively. Pathologic residual cervical tumor was the single independent factor decreasing the probability of DFS (p = 0.020). Acute toxicities were moderate. Two severe ureteral complications requiring surgical intervention were observed. Conclusions: Concomitant chemoradiation followed by surgery for operable bulky stage I-II cervical carcinoma without clinical lymph node involvement can be used with acceptable toxicity. Pathologic complete response increases the probability of DFS.

  4. More Accurate Definition of Clinical Target Volume Based on the Measurement of Microscopic Extensions of the Primary Tumor Toward the Uterus Body in International Federation of Gynecology and Obstetrics Ib-IIa Squamous Cell Carcinoma of the Cervix

    SciTech Connect

    Xie, Wen-Jia; Wu, Xiao; Xue, Ren-Liang; Lin, Xiang-Ying; Kidd, Elizabeth A.; Yan, Shu-Mei; Zhang, Yao-Hong; Zhai, Tian-Tian; Lu, Jia-Yang; Wu, Li-Li; Zhang, Hao; Huang, Hai-Hua; Chen, Zhi-Jian; Li, De-Rui; Xie, Liang-Xi

    2015-01-01

    Purpose: To more accurately define clinical target volume for cervical cancer radiation treatment planning by evaluating tumor microscopic extension toward the uterus body (METU) in International Federation of Gynecology and Obstetrics stage Ib-IIa squamous cell carcinoma of the cervix (SCCC). Patients and Methods: In this multicenter study, surgical resection specimens from 318 cases of stage Ib-IIa SCCC that underwent radical hysterectomy were included. Patients who had undergone preoperative chemotherapy, radiation, or both were excluded from this study. Microscopic extension of primary tumor toward the uterus body was measured. The association between other pathologic factors and METU was analyzed. Results: Microscopic extension toward the uterus body was not common, with only 12.3% of patients (39 of 318) demonstrating METU. The mean (±SD) distance of METU was 0.32 ± 1.079 mm (range, 0-10 mm). Lymphovascular space invasion was associated with METU distance and occurrence rate. A margin of 5 mm added to gross tumor would adequately cover 99.4% and 99% of the METU in the whole group and in patients with lymphovascular space invasion, respectively. Conclusion: According to our analysis of 318 SCCC specimens for METU, using a 5-mm gross tumor volume to clinical target volume margin in the direction of the uterus should be adequate for International Federation of Gynecology and Obstetrics stage Ib-IIa SCCC. Considering the discrepancy between imaging and pathologic methods in determining gross tumor volume extent, we recommend a safer 10-mm margin in the uterine direction as the standard for clinical practice when using MRI for contouring tumor volume.

  5. Cyberknife treatment for advanced or terminal stage hepatocellular carcinoma

    PubMed Central

    Kato, Hiroyuki; Yoshida, Hideo; Taniguch, Hiroyoshi; Nomura, Ryutaro; Sato, Kengo; Suzuki, Ichiro; Nakata, Ryo

    2015-01-01

    AIM: To investigate the safety and efficacy of the Cyberknife treatment for patients with advanced or terminal stage hepatocellular carcinoma (HCC). METHODS: Patients with HCC with extrahepatic metastasis or vascular or bile duct invasion were enrolled between May 2011 and June 2015. The Cyberknife was used to treat each lesion. Treatment response scores were based on Response Evaluation Criteria in Solid Tumors v1.1. The trends of tumor markers, including alpha fetoprotein (AFP) and proteins induced by vitamin K absence II (PIVKA II) were assessed. Prognostic factors for tumor response and tumor markers were evaluated with Fisher’s exact test and a logistic regression model. Survival was evaluated with the Kaplan-Meier method and multivariate analysis was performed using the Cox proportional hazards model. RESULTS: Sixty-five patients with 95 lesions were enrolled. Based on the Barcelona Clinic Liver Cancer classification, all patients were either in the advanced or terminal stage of the disease. The target lesions were as follows: 52 were bone metastasis; 9, lung metastasis; 7, brain metastasis; 9, portal vein invasion; 4, hepatic vein invasion; 4, bile duct invasion; and 10 other lesion types. The response rate and disease control rate were 34% and 53%, respectively. None of the clinical factors correlated significantly with tumor response. Fiducial marker implantation was associated with better control of both AFP (HR = 0.152; 95%CI: 0.026-0.887; P = 0.036) and PIVKA II (HR = 0.035; 95%CI: 0.003-0.342; P = 0.004). The median survival time was 9 mo (95%CI: 5-15 mo). Terminal stage disease (HR = 9.809; 95%CI: 2.589-37.17, P < 0.001) and an AFP of more than 400 ng/mL (HR = 2.548; 95%CI: 1.070-6.068, P = 0.035) were associated with worse survival. A radiation dose higher than 30 Gy (HR = 0.274; 95%CI: 0.093-0.7541, P = 0.012) was associated with better survival. In the 52 cases of bone metastasis, 36 patients (69%) achieved pain relief. One patient had cerebral

  6. MLN0264 in Previously Treated Asian Patients With Advanced Gastrointestinal Carcinoma or Metastatic or Recurrent Gastric or Gastroesophageal Junction Adenocarcinoma Expressing Guanylyl Cyclase C

    ClinicalTrials.gov

    2016-06-03

    Advanced Gastrointestinal Carcinoma; Gastroesophageal Junction Adenocarcinoma; Recurrent Gastric Adenocarcinoma; Recurrent Gastroesophageal Junction Adenocarcinoma; Metastatic Gastric Adenocarcinoma; Metastatic Gastroesophageal Junction Adenocarcinoma; Recurrent Gastrointestinal Carcinoma

  7. Recent advances in the surgical treatment of hepatocellular carcinoma.

    PubMed

    Morise, Zenichi; Kawabe, Norihiko; Tomishige, Hirokazu; Nagata, Hidetoshi; Kawase, Jin; Arakawa, Satoshi; Yoshida, Rie; Isetani, Masashi

    2014-10-21

    Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. The treatment of HCC is complex and complicated by the severity of associated chronic liver disease, the stage of HCC, and the clinical condition of the patient. Liver resection (LR) is one of the most efficient treatments for patients with HCC, with an expected 5-year survival of 38%-61% depending on the stage of the disease. Improved liver function assessment, increased understanding of segmental liver anatomy from advanced imaging studies, and surgical technical progress are important factors that have led to reduced mortality in patients with HCC. The indication for LR may be expanded due to emerging evidences from laparoscopic hepatectomies and combined treatments with newly developed chemotherapies. Liver transplantation (LT) is considered as an ideal treatment for removal of existing tumors and the injured/preneoplastic underlying liver tissue with impaired liver function and the risk of multicentric carcinogenesis that results from chronically injured liver. However, LT is restricted to patients with minimal risk of tumor recurrence under immunosuppression. The expansion of criteria for LT in HCC patients is still under trial and discussion. Limited availability of grafts, as well as the risk and the cost of transplantation have led to considerable interest in expansion of the donor pool, living donor-related transplantation, and combined treatment involving LR and LT. This highlight presents evidence concerning recent studies evaluating LR and LT in HCC patients. In addition, alternative therapies for the treatment of early stage tumors and the management of patients on transplant waiting lists are discussed. PMID:25339825

  8. A Challenging Surgical Approach to Locally Advanced Primary Urethral Carcinoma

    PubMed Central

    Lucarelli, Giuseppe; Spilotros, Marco; Vavallo, Antonio; Palazzo, Silvano; Miacola, Carlos; Forte, Saverio; Matera, Matteo; Campagna, Marcello; Colamonico, Ottavio; Schiralli, Francesco; Sebastiani, Francesco; Di Cosmo, Federica; Bettocchi, Carlo; Di Lorenzo, Giuseppe; Buonerba, Carlo; Vincenti, Leonardo; Ludovico, Giuseppe; Ditonno, Pasquale; Battaglia, Michele

    2016-01-01

    Abstract Primary urethral carcinoma (PUC) is a rare and aggressive cancer, often underdetected and consequently unsatisfactorily treated. We report a case of advanced PUC, surgically treated with combined approaches. A 47-year-old man underwent transurethral resection of a urethral lesion with histological evidence of a poorly differentiated squamous cancer of the bulbomembranous urethra. Computed tomography (CT) and bone scans excluded metastatic spread of the disease but showed involvement of both corpora cavernosa (cT3N0M0). A radical surgical approach was advised, but the patient refused this and opted for chemotherapy. After 17 months the patient was referred to our department due to the evidence of a fistula in the scrotal area. CT scan showed bilateral metastatic disease in the inguinal, external iliac, and obturator lymph nodes as well as the involvement of both corpora cavernosa. Additionally, a fistula originating from the right corpus cavernosum extended to the scrotal skin. At this stage, the patient accepted the surgical treatment, consisting of different phases. Phase I: Radical extraperitoneal cystoprostatectomy with iliac-obturator lymph nodes dissection. Phase II: Creation of a urinary diversion through a Bricker ileal conduit. Phase III: Repositioning of the patient in lithotomic position for an overturned Y skin incision, total penectomy, fistula excision, and “en bloc” removal of surgical specimens including the bladder, through the perineal breach. Phase IV: Right inguinal lymphadenectomy. The procedure lasted 9-and-a-half hours, was complication-free, and intraoperative blood loss was 600 mL. The patient was discharged 8 days after surgery. Pathological examination documented a T4N2M0 tumor. The clinical situation was stable during the first 3 months postoperatively but then metastatic spread occurred, not responsive to adjuvant chemotherapy, which led to the patient's death 6 months after surgery. Patients with advanced stage tumors of

  9. Comparison of the CO2 laser and Leep-Loop method in treatment of changes in uterine cervix

    NASA Astrophysics Data System (ADS)

    Wozniak, Jakub; Wilczak, Maciej; Sajdak, Stefan; Opala, Tomasz; Rabiega, Dorota

    2000-11-01

    Electric leep-loop and lasersurgery are modern methods in treatment of diseases of uterine cervix that we can use often exchangeable. Differences first of all relates indications. Lasersurgery we can apply in diseases of uterine cervix channel. Application of electric leep in dysplasia of small grade of uterus cervix channel is possible. Before lasersurgery we should exclude cervical carcinoma, because we don't have histopathological material. Leep-loop conisation we shouldn't apply at young women, who plan pregnancy (risk of cicatristaion and dystokia of uterine cervix.)

  10. Recent advances in the management of renal cell carcinoma

    PubMed Central

    Molina, Ana M.; Nanus, David M.

    2016-01-01

    Therapeutic options for patients with metastatic renal cell carcinoma have significantly improved over the past few years with the recent approval of two new agents resulting in prolonged progression-free and overall survival. PMID:27019698

  11. Galectin-1 Is an Independent Prognostic Factor for Local Recurrence and Survival After Definitive Radiation Therapy for Patients With Squamous Cell Carcinoma of the Uterine Cervix

    SciTech Connect

    Huang, Eng-Yen; Chanchien, Chan-Chao; Lin, Hao; Wang, Chung-Chi; Wang, Chong-Jong; Huang, Chao-Cheng

    2013-12-01

    Purpose: To investigate the role of galectin-1 in patients with cervical cancer after definitive radiation therapy. Methods and Materials: We reviewed 154 patients with International Federation of Gynecology and Obstetrics stage I-II squamous cell carcinoma. Patients underwent curative-intent radiation therapy. Paraffin-embedded tissues were analyzed using immunohistochemistry staining for galectin-1. The rates of cancer-specific survival (CSS), local recurrence (LR), and distant metastasis were compared among patient tissue samples with no, weak, and strong galectin-1 expression. The Kaplan-Meier method and the Cox proportional hazard model with hazard ratios and 95% confidence intervals (CIs) were used for univariate and multivariate analyses, respectively. Results: The areas under the curve for the intracellular expression scores of galectin-1 for both LR and CSS were significantly higher than those for stromal expression. There were no significant differences in the demographic data, such as stage and serum tumor markers, between patients with and without intracellular expression of galectin-1 in cancer tissue samples. Using multivariate analyses, the hazard ratios of LR and CSS were 2.60 (95% CI 1.50-4.52) (P=.001) and 1.94 (95% CI 1.18-3.19) (P=.010), respectively. Conclusion: Galectin-1 is an independent prognostic factor associated with LR and CSS in stage I-II cervical cancer patients undergoing definitive radiation therapy. Further studies targeting galectin-1 may improve the local control of cervical cancer.

  12. Hedgehog- and mTOR-targeted therapies for advanced basal cell carcinomas.

    PubMed

    Piérard-Franchimont, Claudine; Hermanns-Lê, Trinh; Paquet, Philippe; Herfs, Michael; Delvenne, Philippe; Piérard, Gérald E

    2015-11-01

    Basal cell carcinomas (BCCs) are the most frequent human cancer. Over 90% of all BCCs have a mutation in PTCH1 or smoothened, two conducting proteins of the Hedgehog pathway. They rarely progress deeply and metastasize; however, if they do, these advanced basal cell carcinoma become amenable to treatment by inhibiting the Hedgehog and the P13K-mTOR pathways. Such innovative drugs include vismodegib, cyclopamine, itraconazole, everolimus and a few other agents that are in early clinical development. PMID:26437034

  13. Optical diagnosis of mammary ductal carcinoma using advanced optical technology

    NASA Astrophysics Data System (ADS)

    Wu, Yan; Fu, Fangmeng; Lian, Yuane; Nie, Yuting; Zhuo, Shuangmu; Wang, Chuan; Chen, Jianxin

    2015-02-01

    Clinical imaging techniques for diagnosing breast cancer mainly include X-ray mammography, ultrasound, and magnetic resonance imaging (MRI), which have respective drawbacks. Multiphoton microscopy (MPM) has become a potentially attractive optical technique to bridge the current gap in clinical utility. In this paper, MPM was used to image normal and ductal cancerous breast tissues, based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG). Our results showed that MPM has the ability to exhibit the microstructure of normal breast tissue, ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) lesions at the molecular level comparable to histopathology. These findings indicate that, with integration of MPM into currently accepted clinical imaging system, it has the potential to make a real-time histological diagnosis of mammary ductal carcinoma in vivo.

  14. Hedgehog pathway inhibition in advanced basal cell carcinoma: latest evidence and clinical usefulness.

    PubMed

    Silapunt, Sirunya; Chen, Leon; Migden, Michael R

    2016-09-01

    Treatment of locally advanced basal cell carcinomas (laBCCs) with large, aggressive, destructive, and disfiguring tumors, or metastatic disease is challenging. Dysregulation of the Hedgehog (Hh) signaling pathway has been identified in the vast majority of basal cell carcinomas (BCCs). There are two United States Food and Drug Administration (US FDA)-approved Hh pathway inhibitors (HPIs) that exhibit antitumor activity in advanced BCC with an acceptable safety profile. Common adverse effects include muscle spasms, dysgeusia, alopecia, fatigue, nausea and weight loss. PMID:27583029

  15. Hedgehog pathway inhibition in advanced basal cell carcinoma: latest evidence and clinical usefulness

    PubMed Central

    Silapunt, Sirunya; Chen, Leon; Migden, Michael R.

    2016-01-01

    Treatment of locally advanced basal cell carcinomas (laBCCs) with large, aggressive, destructive, and disfiguring tumors, or metastatic disease is challenging. Dysregulation of the Hedgehog (Hh) signaling pathway has been identified in the vast majority of basal cell carcinomas (BCCs). There are two United States Food and Drug Administration (US FDA)-approved Hh pathway inhibitors (HPIs) that exhibit antitumor activity in advanced BCC with an acceptable safety profile. Common adverse effects include muscle spasms, dysgeusia, alopecia, fatigue, nausea and weight loss. PMID:27583029

  16. Control of cancer of the cervix uteri. A WHO meeting.

    PubMed

    1986-01-01

    Cancer of the uterine cervix is a global problem. It is the most common cancer in women in developing countries and is the second most common cancer in women worldwide, with approximately half a million new cases each year. It is strongly linked with an early onset of sexual activity and multiple sexual partners; recent evidence points to a causal link between some of the precursor lesions of this cancer and specific papillomavirus infections. Cervical cancer has significant morbidity and mortality if it is not detected before it reaches an advanced stage with symptoms. If the disease is detected in an early asymptomatic stage it is nearly always curable by surgery or radiotherapy. Therefore today, cytological screening is the mainstay for control of cervical cancer.In some developed countries, screening programmes for cervical carcinoma have been in operation for many years. In places where large well-organized programmes have been functioning, significant decreases in mortality, in the range of 50-60%, have been observed. The favourable effects result primarily from the removal of intraepithelial lesions preventing the occurrence of invasive tumours.In countries where resources are limited, the aim should be to screen every woman once in her lifetime between 35 and 40 years of age. When more resources are available the frequency of screening should be increased to once every ten or five years for the age groups 35 to 55 years and, ideally, once every three years for women aged between 25 and 60 years.

  17. Intraductal Carcinoma of the Prostate Gland: Recent Advances

    PubMed Central

    Divatia, Mukul K.

    2016-01-01

    Intraductal carcinoma of the prostate (IDC-P) is characterized by prostatic carcinoma involving ducts and/or acini. The presence of IDC-P is usually associated with a high-grade Gleason score, large tumor volume, and adverse prognostic parameters, including extraprostatic extension and seminal vesicle invasion. When present, IDC-P is associated with worse outcomes, regardless of treatment status. IDC-P is included in a broader diagnostic category of atypical cribriform lesions of the prostate gland. This category of lesions also includes high-grade prostatic intraepithelial neoplasia (HGPIN), urothelial carcinoma involving prostatic ducts or acini, and prostatic ductal adenocarcinoma, amongst other intraductal proliferations. Differentiating between these entities is important as they have differing therapeutic and prognostic implications for patients, although differential diagnosis thereof is not always straightforward. The present review discusses IDC-P in regards to its morphological characteristics, molecular features, and clinical outcomes. Given the current state of knowledge, the presence of IDC-P should be evaluated and documented correctly in both radical prostatectomy and needle biopsy specimens, and the clinical implications thereof should be taken into consideration during treatment and follow up. PMID:27401634

  18. Partial atrial resection in advanced lung carcinoma with and without cardiopulmonary bypass.

    PubMed Central

    Shirakusa, T; Kimura, M

    1991-01-01

    Combined pneumonectomy and partial resection of the left atrium was performed in 12 patients with advanced lung carcinoma (T3 and T4 in the new UICC classification). In the eight patients with a T3 lung carcinoma intrapericardial atrial resection with vascular clamping was carried out; four of the patients died within a year. The remaining four patients had a T4 tumour and underwent removal of the right lung and part of the left atrium under total cardiopulmonary bypass. One patient died shortly after the operation from cerebral and cerebellar infarction, and one died 11 months later from brain metastases. Two are alive and well. Complete resection appears to offer a chance for longer survival in patients with advanced lung carcinoma that extends directly into the intrapericardial pulmonary vessels or atrium. Images PMID:1652165

  19. Trimodality Therapy for an Advanced Thymic Carcinoma With Both Aorta and Vena Cava Invasion.

    PubMed

    Momozane, Tohru; Inoue, Masayoshi; Shintani, Yasushi; Funaki, Soichiro; Kawamura, Tomohiro; Minami, Masato; Shirakawa, Yukitoshi; Kuratani, Toru; Sawa, Yoshiki; Okumura, Meinoshin

    2016-08-01

    A case of locally advanced thymic carcinoma that was successfully resected with the great vessels after chemoradiation therapy is reported. A 57-year-old man with Masaoka stage III thymic carcinoma received two cycles of cisplatin/docetaxel and 60 Gy irradiation. The response was stable disease with 19% size reduction, and a radical resection with the ascending aorta and superior vena cava with the patient under circulatory arrest with the use of cardiopulmonary bypass was performed. The postoperative course was uneventful, and the patient has been free of disease for 28 months. Trimodality therapy with use of a cardiovascular surgical procedure might be a valuable option in locally advanced thymic carcinoma. PMID:27449450

  20. An Extremely Rare Case of Advanced Metastatic Small Cell Neuroendocrine Carcinoma of Sinonasal Tract

    PubMed Central

    Guevara, Elizabeth

    2016-01-01

    Small cell neuroendocrine carcinoma (SNEC) is a rare form of malignancy. It mainly presents as bronchogenic neoplasm, and the extrapulmonary form accounts for only 0.1% to 0.4% of all cancers. These extrapulmonary tumors have been described most frequently in the urinary bladder, prostate, esophagus, stomach, colon and rectum, gall bladder, head and neck, cervix, and skin. Primary SNEC of the sinonasal tract is extremely rare with only less than 100 cases reported in the literature. Because of extreme rarity and aggressiveness of the tumor, the management for this entity varies considerably mandating multimodality approach. In this paper, we report a patient presented with left-sided facial swelling, and the histopathologic examination confirmed primary SNEC of left sinonasal tract. The tumor involved multiple paranasal sinuses with invasion into the left orbit and left infratemporal fossa and metastasized to cervical lymph nodes and bone. The patient encountered devastating outcome in spite of optimal medical management and treatment with palliative chemotherapy highlighting the necessity for further research of primary SNEC of head and neck. PMID:27529044

  1. An Extremely Rare Case of Advanced Metastatic Small Cell Neuroendocrine Carcinoma of Sinonasal Tract.

    PubMed

    Thar, Yu Yu; Patel, Poras; Huang, Tiangui; Guevara, Elizabeth

    2016-01-01

    Small cell neuroendocrine carcinoma (SNEC) is a rare form of malignancy. It mainly presents as bronchogenic neoplasm, and the extrapulmonary form accounts for only 0.1% to 0.4% of all cancers. These extrapulmonary tumors have been described most frequently in the urinary bladder, prostate, esophagus, stomach, colon and rectum, gall bladder, head and neck, cervix, and skin. Primary SNEC of the sinonasal tract is extremely rare with only less than 100 cases reported in the literature. Because of extreme rarity and aggressiveness of the tumor, the management for this entity varies considerably mandating multimodality approach. In this paper, we report a patient presented with left-sided facial swelling, and the histopathologic examination confirmed primary SNEC of left sinonasal tract. The tumor involved multiple paranasal sinuses with invasion into the left orbit and left infratemporal fossa and metastasized to cervical lymph nodes and bone. The patient encountered devastating outcome in spite of optimal medical management and treatment with palliative chemotherapy highlighting the necessity for further research of primary SNEC of head and neck. PMID:27529044

  2. [Extended prevention of uterine cervix cancer].

    PubMed

    Müller, H G

    1979-01-01

    A transverse-oval os uteri or Emmet' tear are the result of a tear at the mouth of the womb during final cervical dilatation. Furthermore, they are the cause of a more or less developed ectopia and combined cervical and vaginal fluor with concomitant colpitis. These alterations also represent the foundation not the cause, of a development of cervical carcinoma. In the sense of prophylactic reasoning the elimination of the symptoms mentioned above should be considered. -- The use of the speculum and care of the suture of the nearly always torn os uteri after each delivery must be the first step to avoid the development of a collum carcinoma. -- In the second place, electrocoagulation or shallow conisation with subsequent coagulation and cryo-surgical treatment of the ectopia has to be carried out. -- Therefore the obstetrician decides whether the patient -- in view of developing a collum carcinoma -- becomes a risk patient. He has to ensure that an almost normal portio uteri returns without ectropion and Emmet'tear and also without cervical and vaginal fluor, which could trouble the patient considerably. -- After every delivery, therefore, the speculum should be used. At the same time a cervix tear haemorrhage, one of the most frequent exsanguinations, can be avoided.

  3. [Platin-containing cytostatic combinations in the therapy of advanced gynecologic carcinomas].

    PubMed

    Schulz, B O; Hof, K; Friedrich, H J; Weppelmann, B; Krebs, D

    1984-01-01

    95 patients with advanced and recurred gynecological carcinomas (57 ovarian carcinoma, 22 cervical carcinoma) were treated by a platinum (CDDP) based polychemotherapy platinum, adriamycine, cyclophosphamide (PAC); platinum, adriamycine, bleomycine (PAB), 22 out of 48 patients with low differentiated epithelial carcinoma of the ovary stage III and IV achieved a remission (13 CR; 9 PR). Today 6 of the CR-patients survive 23 months without recurrence; 7 had a medium survival of 17 months. Medium survival of PR-patients was 15 months. 6 NED-patients survive 22 months without recurrence and 2 NED-patients died after 19,5 months. The overall response rate (CR, PR, NED) was 63%. A retrospective comparison with 78 patients (low differentiated ovarian carcinoma stage III and IV) treated by a cyclophosphamide monotherapy shows an elevated 2-year survival rate of the PAC treated patients. The other patients suffered from carcinoma of the mamma, the tubes, the corpus uteri, the vagina, and the vulva. The therapeutic effect of CDDP based polychemotherapy cannot be judged because of the small number of cases; but the side effects at these patients were registered thoroughly. Side effects of totally 514 therapeutic cycles (460 mg CDDP per patient, 78 mg CDDP per cycle) are presented.

  4. Targeted treatments in advanced renal cell carcinoma: focus on axitinib

    PubMed Central

    Verzoni, Elena; Grassi, Paolo; Testa, Isabella; Iacovelli, Roberto; Biondani, Pamela; Garanzini, Enrico; De Braud, Filippo; Procopio, Giuseppe

    2014-01-01

    Antiangiogenesis options have evolved rapidly in the last few years, with an increasing number of agents currently approved by the US Food and Drug Administration and European Medicines Agency. Angiogenesis inhibitors have been shown to be very effective for the treatment of metastatic renal cancer cell. Axitinib is a third-generation inhibitor of vascular endothelial growth factor receptor and is currently being developed for the treatment of various malignancies. The pharmacokinetic properties of axitinib may have a selective therapeutic effect, with minimal adverse reactions and enhanced safety. In a large Phase III study of previously treated patients with metastatic renal cell carcinoma, axitinib achieved a longer progression-free survival than sorafenib with an acceptable safety profile and good quality of life. This review focuses on the pharmacology, pharmacokinetics, and clinical activity of axitinib in the current treatment of renal cell carcinoma. The role of axitinib in the adjuvant and/or neoadjuvant setting needs to be evaluated in further clinical trials. PMID:24715765

  5. Persistent Uroplakin Expression in Advanced Urothelial Carcinomas: Implications in Urothelial Tumor Progression and Clinical Outcome

    PubMed Central

    Huang, Hong-Ying; Shariat, Shahrokh F.; Sun, Tung-Tien; Lepor, Herbert; Shapiro, Ellen; Hsieh, Jer-Tsong; Ashfaq, Raheela; Lotan, Yair; Wu, Xue-Ru

    2007-01-01

    As the terminal differentiation products of human urothelium, uroplakins (UPs) would be expected to diminish during urothelial tumorigenesis. Surprisingly, recent studies found UPs to be retained even by well-advanced urothelial carcinomas, suggesting that the loss of UPs does not strictly parallel urothelial transformation. Little is known, however, about whether the status of UPs is associated with a particular pathological parameter, tumor’s biological behavior or patient outcome. Here we assessed UP expression by immunohistochemistry on tissue arrays from 285 patients with bladder urothelial carcinomas or non-tumor conditions. UPs were expressed in all 9 normal urothelial specimens, 63/74 (85%) patients with non-muscle-invasive urothelial carcinomas on transurethral resection, 104/202 (51.5%) patients who underwent radical cystectomy for advanced urothelial carcinomas, and 33/50 (66%) lymph node metastases. Normally associated with urothelial apical surface, UPs were localized aberrantly in tumors, including micro-luminal, basal-laminal, cytoplasmic or uniform patterns. In non-muscle-invasive diseases, there was no association between UP expression and disease recurrence, progression or mortality. In contrast, in invasive diseases, absent UP expression was significantly associated with advanced pathologic stage, lymph node metastases, disease recurrence and bladder cancer-specific mortality (p=0.042, p=0.035, p=0.023 and p=0.022, respectively) in univariate analyses. Furthermore, UP status was independent of key cell-cycle regulators, including p53, pRb, p27 and cyclin D1, thus excluding a functional link between these two groups of proteins. Our data demonstrate for the first time that persistent UP expression is associated with a favorable clinical outcome and that UPs may be used as adjunct markers for predicting the prognoses of patients with invasive and metastatic bladder carcinomas. Our results also suggest that UP-positive and –negative carcinomas

  6. Nab-paclitaxel as alternative treatment regimen in advanced cholangiocellular carcinoma

    PubMed Central

    Unseld, Matthias; Scheithauer, Werner; Weigl, Roman; Kornek, Gabriela; Stranzl, Nadja; Bianconi, Daniela; Brunauer, Georg; Steger, Guenther; Zielinski, Christoph C.

    2016-01-01

    Background Advanced cholangiocellular carcinoma has a poor prognosis with limited therapeutic options. Nab-paclitaxel has recently been described to be beneficial in metastatic pancreatic cancer improving overall and progression free survival (PFS). The potential antitumor activity of nab-paclitaxel in cholangiocellular carcinoma is hitherto unknown. Methods We retrospectively analyzed an institutional cholangiocellular carcinoma registry to determine the potential biological activity of nab-paclitaxel in advanced intrahepatic cholangiocellular carcinoma. Disease control rate (DCR), PFS and overall survival (OS) upon nab-paclitaxel based treatment, after failure of platinum-containing first-line combination chemotherapy, was assessed. Results Twelve patients were identified. Five of 12 patients (42%) received nab-paclitaxel as second line, and 7 patients (56%) as third-line treatment. The objective DCR with nab-paclitaxel was 83% (10/12 patients). One patient had a complete remission (CR), two patients had a partial remission (PR) and 7 patients had stable disease (SD). Disease was rated progressive in two patients. In all 12 patients receiving nab-paclitaxel the median time to progression was 6 months (range, 2.1–19.5 months). Median OS after initiation of nab-paclitaxel treatment was 9 months (2.1–28.4 months). The median time of survival after diagnosis of advanced disease was 21.5 months, whereby 3 patients were alive at the date of censoring (04/01/2015). Conclusions This is the first report suggesting substantial antitumor activity of nab-paclitaxel in advanced cholangiocellular carcinoma. In this small series, nab-paclitaxel based salvage chemotherapy appears to have a biological activity by controlling the disease and positively affecting survival. Randomized trials in this disease entity and subgroup of patients are urged. PMID:27563449

  7. Phase II Study of Carboplatin and Paclitaxel in Advanced Thymoma and Thymic Carcinoma

    PubMed Central

    Lemma, Girum L.; Lee, Ju-Whei; Aisner, Seena C.; Langer, Corey J.; Tester, William J.; Johnson, David H.; Loehrer, Patrick J.

    2011-01-01

    Purpose The purpose of this study was to evaluate the impact of carboplatin and paclitaxel in patients with advanced previously untreated thymoma and thymic carcinoma. Patients and Methods We conducted a prospective multicenter study in patients with unresectable thymoma (n = 21) or thymic carcinoma (n = 23). Patients were treated with carboplatin (area under the curve, 6) plus paclitaxel (225 mg/m2) every 3 weeks for a maximum of six cycles. The primary end point of this trial was to evaluate the objective response rate. Results From February 2001 through January 2008, 46 patients were enrolled. Thirteen patients had grade 4 or greater toxicity, mostly neutropenia. Using RECIST (Response Evaluation Criteria in Solid Tumors) 1.0 criteria, three complete responses (CRs) and six partial responses (PRs; objective response rate [ORR], 42.9%; 90% CI, 24.5% to 62.8%) were observed in the thymoma cohort; 10 patients had stable disease. For patients with thymic carcinoma, no CRs and five PRs (ORR, 21.7%; 90% CI, 9.0% to 40.4%) were observed; 12 patients had stable disease. Progression-free survival (PFS) was 16.7 (95% CI, 7.2 to 19.8) and 5.0 (95% CI, 3.0 to 8.3) months for thymoma and thymic carcinoma cohorts, respectively. To date, only seven patients (33.3%) with thymoma have died, compared with 16 patients (69.6%) with thymic carcinoma. Median survival time was 20.0 months (95% CI, 5.0 to 43.6 months) for patients with thymic carcinoma, but it has not been reached for patients with thymoma. Conclusion Carboplatin plus paclitaxel has moderate clinical activity for patients with thymic malignancies, but this seems less than expected with anthracycline-based therapy. Patients with thymic carcinoma have poorer PFS and overall survival than patients with thymoma. PMID:21502559

  8. Urothelial cells in smears from cervix uteri

    PubMed Central

    Palaoro, Luis Alberto; Guerra, Fernando; Angeleri, Anabela; Palamas, Marta; Melba, Sardi-Segovia; Rocher, Adriana Esther

    2012-01-01

    Objectives: To establish the cytological criteria to identify the urothelial cells in cervical smears in order to avoid mistakes in the cytological diagnosis. Materials and Methods: Cervical smears from 34 post menopausal women with vesicovaginal fistulas, advanced bladder prolapse and genital erosive lichen planes (vulvar kraurosis) (Group 1) and transitional cell metaplasia of the cervix (TCM, Group 2) were stained with Papanicolaou technique. The cervical samples were taken during the routine annual examination for prevention of the uterine cancer. Results: The smears of cervix from Group 1 showed urothelial cells from the three layers of the transitional epithelium. The umbrella cells are the bigger ones with relatively large nuclei. Frequently, they are multinucleated with single or multiple nucleoli and a typical “frothy” cytoplasm (cytoplasmic vacuoles). The cells of the Group 2 showed nuclei with oval to spindled shapes, some tapered ends, less cytoplasm than squamous metaplastic cells, powdery chromatin, small nucleoli and nuclear grooves. Conclusions: The umbrella cells may be mistaken for dysplastic cells originating in low grade squamous intraepithelial lesions lesions (LSILs) due to their nuclear and cytoplasm sizes. Therefore, it is important to know the possibility of their appearance in the cervical smears, especially in post menopausal patients in order to avoid a false diagnosis of an intraepithelial lesion. It is unlikely that deeper cells of urothelium would be confused with high grade squamous intraepithelial lesion (HSIL) cells. However, their presence might be a reason of mistake in the diagnosis. TCM is an under-recognized metaplastic phenomenon of the cervix and vagina, which is a mimicker of high-grade squamous intraepithelial lesion. The differential characteristic between umbrella cells, cells from TCM and the deeper urothelial cells, and LSIL and HSIL are detailed in the present paper. PMID:22438615

  9. Lectin cytochemistry in the exfoliative cytology of uterine cervix.

    PubMed

    Remani, P; Pillai, K R; Haseenabeevi, V M; Ankathil, R; Bhattathiri, V N; Nair, M K; Vijayakumar, T

    1994-01-01

    A lectin was isolated from the seeds of jack fruit (Artocarpus integrifolia) and purified using a column of immobilized N-acetyl-D-galactosamine. This jack fruit lectin (JFL) was then conjugated to horse-radish peroxidase (HRP) type VI and used to study the cell surface carbohydrate profile of the cytological smears of the uterine cervix using diaminobenzidine as substrate. Cervical smears from 15 healthy individuals and 65 patients with dysplasia, carcinoma in situ and carcinoma of uterine cervix were used for the study. Normal cells showed weak binding in the membrane as well as cytoplasm, whereas carcinomatous cells showed strong binding towards JFL. Carcinoma in situ cells showed a binding pattern similar to that of carcinoma. Dysplastic cells showed difference in binding in mild, moderate and severe dysplasia. The intensity of binding increased with the severity of the dysplasia. The nature and intensity of binding of jack fruit lectin with cancer tissues suggest that this lectin may be of use as a diagnostic aid in exfoliative cytology.

  10. Advanced oxidation protein products and total antioxidant activity in colorectal carcinoma.

    PubMed

    Avinash, S S; Anitha, M; Vinodchandran; Rao, Gayathri M; Sudha, K; Shetty, Beena V

    2009-01-01

    The present study was designed to assess the levels of advanced oxidation protein products (AOPP) and percent hemolysis (that indirectly indicates the degree of membrane damage secondary to lipid peroxidation) in colorectal carcinoma. Glutathione (GSH), total thiols and albumin were measured to determine the antioxidant status. Considering the dynamic interaction between various antioxidants in the body, we measured the total antioxidant activity (AOA). Globulin was measured to assess the inflammatory response secondary to oxidative stress. Investigations were conducted in 45 cases of recently diagnosed primary colorectal adenocarcinoma. As control, 45 age and sex matched healthy persons were chosen. GSH was estimated in whole blood, percent hemolysis in RBC suspension and other parameters in plasma. We observed a very high significant increase (P<0.001) in AOPP, percent hemolysis and a highly significant increase (P<0.01) in globulin in colorectal carcinoma. We observed a very high significant decrease (P<0.001) in whole blood GSH, total thiols, albumin, AOA and a significant decrease (P<0.05) in plasma GSH in colorectal carcinoma. A very high significant negative correlation between percent hemolysis and AOA and an apparent negative correlation between total thiols and AOPP was seen in colorectal carcinoma. This demonstrated oxidative stress, decreased antioxidant status and secondary inflammatory response in colorectal carcinoma.

  11. Epithelial plasticity in urothelial carcinoma: Current advancements and future challenges

    PubMed Central

    Garg, Minal

    2016-01-01

    Urothelial carcinoma (UC) of the bladder is characterized by high recurrence rate where a subset of these cells undergoes transition to deadly muscle invasive disease and later metastasizes. Urothelial cancer stem cells (UroCSCs), a tumor subpopulation derived from transformation of urothelial stem cells, are responsible for heterogeneous tumor formation and resistance to systemic treatment in UC of the bladder. Although the precise reason for pathophysiologic spread of tumor is not clear, transcriptome analysis of microdissected cancer cells expressing multiple progenitor/stem cell markers validates the upregulation of genes that derive epithelial-to-mesenchymal transition. Experimental studies on human bladder cancer xenografts describe the mechanistic functions and regulation of epithelial plasticity for its cancer-restraining effects. It has been further examined to be associated with the recruitment of a pool of UroCSCs into cell division in response to damages induced by adjuvant therapies. This paper also discusses the various probable therapeutic approaches to attenuate the progressive manifestation of chemoresistance by co-administration of inhibitors of epithelial plasticity and chemotherapeutic drugs by abrogating the early tumor repopulation as well as killing differentiated cancer cells. PMID:27621760

  12. Epithelial plasticity in urothelial carcinoma: Current advancements and future challenges

    PubMed Central

    Garg, Minal

    2016-01-01

    Urothelial carcinoma (UC) of the bladder is characterized by high recurrence rate where a subset of these cells undergoes transition to deadly muscle invasive disease and later metastasizes. Urothelial cancer stem cells (UroCSCs), a tumor subpopulation derived from transformation of urothelial stem cells, are responsible for heterogeneous tumor formation and resistance to systemic treatment in UC of the bladder. Although the precise reason for pathophysiologic spread of tumor is not clear, transcriptome analysis of microdissected cancer cells expressing multiple progenitor/stem cell markers validates the upregulation of genes that derive epithelial-to-mesenchymal transition. Experimental studies on human bladder cancer xenografts describe the mechanistic functions and regulation of epithelial plasticity for its cancer-restraining effects. It has been further examined to be associated with the recruitment of a pool of UroCSCs into cell division in response to damages induced by adjuvant therapies. This paper also discusses the various probable therapeutic approaches to attenuate the progressive manifestation of chemoresistance by co-administration of inhibitors of epithelial plasticity and chemotherapeutic drugs by abrogating the early tumor repopulation as well as killing differentiated cancer cells.

  13. Epithelial plasticity in urothelial carcinoma: Current advancements and future challenges.

    PubMed

    Garg, Minal

    2016-08-26

    Urothelial carcinoma (UC) of the bladder is characterized by high recurrence rate where a subset of these cells undergoes transition to deadly muscle invasive disease and later metastasizes. Urothelial cancer stem cells (UroCSCs), a tumor subpopulation derived from transformation of urothelial stem cells, are responsible for heterogeneous tumor formation and resistance to systemic treatment in UC of the bladder. Although the precise reason for pathophysiologic spread of tumor is not clear, transcriptome analysis of microdissected cancer cells expressing multiple progenitor/stem cell markers validates the upregulation of genes that derive epithelial-to-mesenchymal transition. Experimental studies on human bladder cancer xenografts describe the mechanistic functions and regulation of epithelial plasticity for its cancer-restraining effects. It has been further examined to be associated with the recruitment of a pool of UroCSCs into cell division in response to damages induced by adjuvant therapies. This paper also discusses the various probable therapeutic approaches to attenuate the progressive manifestation of chemoresistance by co-administration of inhibitors of epithelial plasticity and chemotherapeutic drugs by abrogating the early tumor repopulation as well as killing differentiated cancer cells. PMID:27621760

  14. Cabozantinib versus everolimus in advanced renal cell carcinoma

    PubMed Central

    Choueiri, Toni K.; Escudier, Bernard; Powles, Thomas; Mainwaring, Paul; Rini, Brian I.; Donskov, Frede; Hammers, Hans; Hutson, Thomas E.; Lee, Jae-Lyun; Peltola, Katriina; Roth, Bruce J.; Bjarnason, Georg A.; Géczi, Lajos; Keam, Bhumsuk; Moroto, Pablo; Heng, Daniel Y. C.; Schmidinger, Manuela; Kantoff, Philip W.; Borgman, Anne; Hessel, Colin; Scheffold, Christian; Schwab, Gisela M.; Tannir, Nizar M.; Motzer, Robert J.

    2016-01-01

    Background Cabozantinib is an oral small molecule tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR) as well as MET and AXL; each has been implicated in metastatic renal cell carcinoma (RCC) pathobiology or development of resistance to antiangiogenic drugs. This randomized open-label phase 3 trial evaluated the efficacy of cabozantinib compared to everolimus in RCC patients who progressed after VEGFR-targeted therapy. Methods The trial randomized 658 patients to receive cabozantinib at a dose of 60 mg daily, or everolimus at a dose of 10 mg daily. The primary endpoint was progression-free survival. Secondary efficacy endpoints were overall survival and objective response rate. Results Median progression-free survival was 7.4 months with cabozantinib and 3.8 months with everolimus. The risk of progression or death was 42% lower with cabozantinib compared to everolimus (hazard ratio, 0.58; 95% confidence interval [CI] 0.45 to 0.75; P < 0.001). Objective response rates were 21% with cabozantinib and 5% with everolimus (P < 0.001). A planned interim analysis showed that overall survival was improved with cabozantinib (hazard ratio, 0.67; 95% CI, 0.51 to 0.89; P = 0.005) but did not cross the significance boundary. Adverse events (grade 3 or 4, regardless of causality) were reported in 74% of cabozantinib patients and 65% of everolimus patients. Discontinuation of study treatment for adverse events occurred in 9.1% of cabozantinib patients and 10% of everolimus patients. Conclusions Cabozantinib improved progression-free survival compared to everolimus in RCC patients who progressed after VEGFR-targeted therapy. PMID:26406150

  15. Yttrium-90 Radioembolization of Hepatocellular Carcinoma-Performance, Technical Advances, and Future Concepts.

    PubMed

    Molvar, Christopher; Lewandowski, Robert

    2015-12-01

    Hepatocellular carcinoma (HCC) is a lethal tumor, claiming over half a million lives per year. Treatment of HCC is commonly performed without curative intent, and palliative options dominate, including catheter-based therapies, namely, transarterial chemoembolization and yttrium-90 ((90)Y) radioembolization. This review will showcase the performance of (90)Y radioembolization for the treatment of HCC, focusing on recent seminal data and technical advances. In particular, novel radioembolization treatment concepts are discussed and compared with conventional HCC therapy.

  16. Cost-Effectiveness of Cetuximab for Advanced Esophageal Squamous Cell Carcinoma

    PubMed Central

    Bruno, Marco J.; Polinder, Suzanne; Lorenzen, Sylvie; Lordick, Florian; Peppelenbosch, Maikel P.; Spaander, Manon C. W.

    2016-01-01

    Background Costly biologicals in palliative oncology are emerging at a rapid pace. For example, in patients with advanced esophageal squamous cell carcinoma addition of cetuximab to a palliative chemotherapy regimen appears to improve survival. However, it simultaneously results in higher costs. We aimed to determine the incremental cost-effectiveness ratio of adding cetuximab to first-line chemotherapeutic treatment of patients with advanced esophageal squamous cell carcinoma, based on data from a randomized controlled phase II trial. Methods A cost effectiveness analysis model was applied based on individual patient data. It included only direct medical costs from the health-care perspective. Quality-adjusted life-years and incremental cost-effectiveness ratios were calculated. Sensitivity analysis was performed by a Monte Carlo analysis. Results Adding cetuximab to a cisplatin-5-fluorouracil first-line regimen for advanced esophageal squamous cell carcinoma resulted in an the incremental cost-effectiveness ratio of €252,203 per quality-adjusted life-year. Sensitivity analysis shows that there is a chance of less than 0.001 that the incremental cost-effectiveness ratio will be less than a maximum willingness to pay threshold of €40,000 per quality-adjusted life-year, which is representative for the threshold used in The Netherlands and other developed countries. Conclusions Addition of cetuximab to a cisplatin-5-fluorouracil first-line regimen for advanced esophageal squamous cell carcinoma is not cost-effective when appraised according to currently accepted criteria. Cost-effectiveness analyses using outcome data from early clinical trials (i.c. a phase II trial) enable pharmaceutical companies and policy makers to gain early insight into whether a new drug meets the current eligibility standards for reimbursement and thereby potential admittance for use in regular clinical practice. PMID:27100871

  17. Photodynamic therapy (PDT) in advanced inoperable bronchial carcinoma

    NASA Astrophysics Data System (ADS)

    Moghissi, Keyvan; Dixon, Kate; Stringer, Mark R.; Brown, Stanley B.

    1996-12-01

    Objective: To assess the efficacy of PDT to: Palliate symptoms, control disease and extend survival in patients with advanced inoperable cancer. Subject and Method: 55 Males and 23 females aged between 45-81 years (mean 66 years) with inoperable and advanced lung cancer with > 5O. obstructive lesions of the main, lobar or segmental bronchi. Patients had pre-treatment routine clinical radiological, functional and endoscopic assessment with proven histological diagnosis. Protocol of PDT was; Intravenous injection of 2 mg/Kg bodyweight Polyhaematoporphyrin (equivalent to Photofrin) or Photofrin followed 24-72 hours later by illumination of tumour using 630 nm light (Oxford Laser) delivered via an optical fibre with end diffuser. Treatments were carried out under general anaesthesia as a day case procedure. Patients were rebronchoscoped for debridement/retreatment 4-7 days later. Results: There was no treatment related mortality. Two patients developed mild photosensitivity reaction. All patients showed symptomatic improvement with good initial functional and radiological amelioration. Every patient responded to treatment. Seven patients had complete response and negative histology for 3-12 months. After the first treatment average Forced Vital Capacity (FVC) and Forced Expiratory Volume in one second (FEV1) improvement was 0.5 litres and 0.4 litres respectively. Twenty five percent of patients (nr 19) survived more than 2 years, 10'. (nr=8) between 1-2 years and the remaining 51 patients less than a year. Conclusion: PDT should be considered as a therapeutic modality for all stages of lung cancer and is an excellent treatment modality for palliation in advanced bronchial malignancies.

  18. Sonidegib, a novel smoothened inhibitor for the treatment of advanced basal cell carcinoma

    PubMed Central

    Doan, Hung Q; Silapunt, Sirunya; Migden, Michael R

    2016-01-01

    Basal cell carcinoma (BCC) is the most common nonmelanoma skin cancer. If left untreated, BCCs can become locally aggressive or even metastasize. Currently available treatments include local destruction, surgery, and radiation. Systemic options for advanced disease are limited. The Hedgehog (Hh) pathway is aberrantly activated in a majority of BCCs and in other cancers. Hh pathway inhibitors are targeted agents that inhibit the aberrant activation of the Hh pathway, with smoothened being a targeted component. Sonidegib is a novel smoothened inhibitor that was recently approved by the US Food and Drug Administration. This review focuses on BCC pathogenesis and the clinical efficacy of sonidegib for the treatment of advanced BCC. PMID:27695345

  19. Sonidegib, a novel smoothened inhibitor for the treatment of advanced basal cell carcinoma

    PubMed Central

    Doan, Hung Q; Silapunt, Sirunya; Migden, Michael R

    2016-01-01

    Basal cell carcinoma (BCC) is the most common nonmelanoma skin cancer. If left untreated, BCCs can become locally aggressive or even metastasize. Currently available treatments include local destruction, surgery, and radiation. Systemic options for advanced disease are limited. The Hedgehog (Hh) pathway is aberrantly activated in a majority of BCCs and in other cancers. Hh pathway inhibitors are targeted agents that inhibit the aberrant activation of the Hh pathway, with smoothened being a targeted component. Sonidegib is a novel smoothened inhibitor that was recently approved by the US Food and Drug Administration. This review focuses on BCC pathogenesis and the clinical efficacy of sonidegib for the treatment of advanced BCC.

  20. Advanced carcinoma of the stomach treated with definitive proton therapy

    SciTech Connect

    Koyama, S.; Kawanishi, N.; Fukutomi, H.; Osuga, T.; Iijima, T.; Tsujii, H.; Kitagawa, T. )

    1990-04-01

    We report the case of a 72-yr-old man who suffered from severe chronic emphysema with poor pulmonary function, and who had advanced cancer of the stomach. Proton beam radiotherapy was applied to the lesion, since surgery was contraindicated. The total dose to the stomach lesion was 61 Gy in 7 wk. The tumor on the stomach regressed, with flattening of the round wall of the lesion. The reactive changes of the proton beam radiotherapy, based on the histopathological examination, revealed extensive tumor necrosis and sparing of vital architecture of normal tissue around the irradiated tumor tissue. Only small clusters of vital or devitalized tumor cells with less than approximately 5% of the whole tumor tissue remained after treatment. We suggest that a high dose of radiation delivered by well-defined proton field could result in an improved therapeutic outcome without undue risk of injury to normal tissue.

  1. Factors related to advanced stage oral squamous cell carcinoma in southern Thailand.

    PubMed

    Kerdpon, D; Sriplung, H

    2001-04-01

    A critical factor that indicates a poor prognosis of oral squamous cell carcinoma (OSCC) is advanced stage disease. This study, therefore, aimed to identify the factors related to advanced stage (TNM staging III, IV) OSCC in Thailand. There were 161 patients with squamous cell carcinoma of the oral cavity and lip (ICD-9 140, 141, 143-5), included in the study. Sixty-two per cent of the patients presented with advanced stage disease. Information on demographic characteristics, risk habits, health-seeking behaviour prior to health care professional (HCP) consultation, tumour characteristics and patient and professional delay was obtained by questionnaire-based interview of the patients. These variables were included as initial variables in a logistic regression to calculate the odds ratio (OR) of advanced versus early stage OSCC. Having traditional herbal medication before HCP consultation significantly increased the risk of advanced stage OSCC (OR 5.77; 95% C.I. 1.25-26.62). Floor of mouth location of tumour was associated with a lower risk of advanced stage disease (OR 0.27; 95% C.I. 0.09-0.82) as was having an ulcer (OR 0.43, 95% C.I. 0.02-0.89). The findings indicate that having traditional herbal medication before HCP consultation increased the risk of advanced stage disease. The lower risk of advanced stage OSCC associated with ulcerative tumours and those on the floor of the mouth may be due to their being more readily detected by the patients. PMID:11287274

  2. High dose intensity combination chemotherapy for advanced epithelial ovarian carcinoma: results of a pilot study.

    PubMed Central

    Sweetenham, J. W.; McKendrick, J. J.; Jones, D. H.; Whitehouse, J. M.; Williams, C. J.

    1990-01-01

    Retrospective studies have recently demonstrated a significant correlation between dose intensity of chemotherapy and response rates and survival in various diseases including epithelial ovarian carcinoma. As part of a proposed randomised trial to assess the effect of dose intensity on outcome in ovarian carcinoma, a pilot study has been undertaken to determine the toxicity and efficacy of the high intensity therapy. Nineteen patients with advanced ovarian carcinoma received initial treatment with cisplatin 120 mg m-2 i.v. day 1, and cyclophosphamide 1,000 mg-2 i.v. day 1, given at 21-day intervals for six cycles. The average relative dose intensity of this therapy is 1.14 when compared with the CHAP regimen. Severe toxicity was experienced by most patients. The median received average relative dose intensity was 0.90, with only one patient receiving treatment to the proposed intensity. Randomised studies of the effect of dose intensity in ovarian carcinoma are essential, but an initial step must be to assess whether the proposed high dose treatment can be delivered. PMID:2155645

  3. Association of PTEN mutation with HPV-negative adenocarcinoma of the uterine cervix.

    PubMed

    Minaguchi, Takeo; Yoshikawa, Hiroyuki; Nakagawa, Shunsuke; Yasugi, Toshiharu; Yano, Tetsu; Iwase, Haruko; Mizutani, Katsumi; Shiromizu, Kenji; Ohmi, Kazuo; Watanabe, Yoh; Noda, Kiichiro; Nishiu, Mieko; Nakamura, Yusuke; Taketani, Yuji

    2004-07-01

    Serous, mucinous, endometrioid, and clear cell adenocarcinomas arise from reproductive organs of mullerian origin. Although the mutation of PTEN, a tumor suppressor, is known to be involved in tumorigenesis of endometrioid adenocarcinomas of the endometrium and ovary, the role of PTEN alteration in endometrioid adenocarcinoma of the cervix remains to be investigated. To elucidate the molecular pathogenesis of cervical adenocarcinoma and adenosquamous carcinoma, and in particular to examine the potential role of PTEN mutation in endometrioid-type cancer of the cervix, we analyzed 32 cervical adeno- or adenosquamous carcinomas (8 endometrioid adenocarcinomas, 14 mucinous adenocarcinomas and 10 adenosquamous carcinomas) for PTEN mutations and HPV infections. PTEN mutation was detected in 2 of 8 (25.0%) endometrioid cases, 2 of 14 (14.3%) mucinous cases, and none of 10 (0%) adenosquamous cases. HPV DNA was detected in 11 out of 18 (61.1%) PTEN wild-type adenocarcinomas and 8 out of 10 (80.0%) adenosquamous carcinomas. Among 11 HPV-negative adenocarcinomas, 40.0% (2/5) endometrioid cases and 33.3% (2/6) mucinous cases were shown to be PTEN mutated, while no cases (0/21) were PTEN-mutant in the remainder (i.e. adenosquamous carcinomas and HPV-positive adenocarcinomas). The current observations suggest that PTEN mutation is frequently detected in HPV-negative adenocarcinomas of the cervix and the most prevalent occurrence of PTEN mutation in endometrioid subtype is keeping with endometrial and ovarian carcinomas.

  4. Efficacy and Tolerability of ABT-869 Versus Sorafenib in Advanced Hepatocellular Carcinoma (HCC)

    ClinicalTrials.gov

    2012-09-07

    Hepatocellular Carcinoma Non-resectable; Hepatocellular Carcinoma Recurrent; Carcinoma, Hepatocellular; Liver Diseases; Neoplasms by Histologic Type; Digestive System Neoplasms; Carcinoma; Liver Neoplasms; Neoplasms; Neoplasms by Site; Digestive System Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial

  5. Third generation tyrosine kinase inhibitors and their development in advanced renal cell carcinoma.

    PubMed

    Bukowski, Ronald M

    2012-01-01

    Angiogenesis in general and the vascular endothelial growth factor (VEGF) signaling axis in particular is a validated target in renal cell carcinoma (RCC). Clear-cell carcinoma of the kidney is now recognized as a malignancy that is sensitive to inhibitors of the VEGF pathway. Treatment options for patients with metastatic renal cell carcinoma have evolved in dramatic fashion over the past 6 years, and a new paradigm has developed. The cytokines interferon-α and interleukin-2 were previously utilized for therapy, but since December 2005, six new agents have been approved in the United States for the treatment of advanced RCC. Two are tyrosine kinase inhibitors (TKI's) including sunitinib and recently pazopanib, and the multikinase inhibitor sorafenib. The current review examines the evolving data with the next generation of TKI's, axitinib and tivozanib being developed for the treatment of advanced RCC. These agents were synthesized to provide increased target specificity and enhanced target inhibition. The preclinical and clinical data are examined, an overview of the development of these TKI's is provided, and discussion plus speculation concerning their potential roles as RCC therapy is provided.

  6. Exome sequencing identifies early gastric carcinoma as an early stage of advanced gastric cancer.

    PubMed

    Kang, Guhyun; Hwang, Woo Cheol; Do, In-Gu; Wang, Kai; Kang, So Young; Lee, Jeeyun; Park, Se Hoon; Park, Joon Oh; Kang, Won Ki; Jang, Jiryeon; Choi, Min-Gew; Lee, Jun Ho; Sohn, Tae Sung; Bae, Jae Moon; Kim, Sung; Kim, Min Ji; Kim, Seonwoo; Park, Cheol Keun; Kim, Kyoung-Mee

    2013-01-01

    Gastric carcinoma is one of the major causes of cancer-related mortality worldwide. Early detection and treatment leads to an excellent prognosis in patients with early gastric cancer (EGC), whereas the prognosis of patients with advanced gastric cancer (AGC) remains poor. It is unclear whether EGCs and AGCs are distinct entities or whether EGCs are the beginning stages of AGCs. We performed whole exome sequencing of four samples from patients with EGC and compared the results with those from AGCs. In both EGCs and AGCs, a total of 268 genes were commonly mutated and independent mutations were additionally found in EGCs (516 genes) and AGCs (3104 genes). A higher frequency of C>G transitions was observed in intestinal-type compared to diffuse-type carcinomas (P = 0.010). The DYRK3, GPR116, MCM10, PCDH17, PCDHB1, RDH5 and UNC5C genes are recurrently mutated in EGCs and may be involved in early carcinogenesis.

  7. From Uniplex to Multiplex Molecular Profiling in Advanced Non-Small Cell Lung Carcinoma.

    PubMed

    Ileana, Ecaterina E; Wistuba, Ignacio I; Izzo, Julie G

    2015-01-01

    Non-small cell lung carcinoma is a leading cause of cancer death worldwide. Understanding the molecular biology of survival and proliferation of cancer cells led to a new molecular classification of lung cancer and the development of targeted therapies with promising results. With the advances of image-guided biopsy techniques, tumor samples are becoming smaller, and the molecular testing techniques have to overcome the challenge of integrating the characterization of a panel of abnormalities including gene mutations, copy-number changes, and fusions in a reduced number of assays using only a small amount of genetic material. This article reviews the current knowledge about the most frequent actionable molecular abnormalities in non-small cell lung carcinoma, the new approaches of molecular analysis, and the implications of these findings in the context of clinical practice.

  8. Endocervical ultrasound applicator for integrated hyperthermia and HDR brachytherapy in the treatment of locally advanced cervical carcinoma

    SciTech Connect

    Wootton, Jeffery H.; Hsu, I-Chow Joe; Diederich, Chris J.

    2011-02-15

    Purpose: The clinical success of hyperthermia adjunct to radiotherapy depends on adequate temperature elevation in the tumor with minimal temperature rise in organs at risk. Existing technologies for thermal treatment of the cervix have limited spatial control or rapid energy falloff. The objective of this work is to develop an endocervical applicator using a linear array of multisectored tubular ultrasound transducers to provide 3-D conformal, locally targeted hyperthermia concomitant to radiotherapy in the uterine cervix. The catheter-based device is integrated within a HDR brachytherapy applicator to facilitate sequential and potentially simultaneous heat and radiation delivery. Methods: Treatment planning images from 35 patients who underwent HDR brachytherapy for locally advanced cervical cancer were inspected to assess the dimensions of radiation clinical target volumes (CTVs) and gross tumor volumes (GTVs) surrounding the cervix and the proximity of organs at risk. Biothermal simulation was used to identify applicator and catheter material parameters to adequately heat the cervix with minimal thermal dose accumulation in nontargeted structures. A family of ultrasound applicators was fabricated with two to three tubular transducers operating at 6.6-7.4 MHz that are unsectored (360 deg.), bisectored (2x180 deg.), or trisectored (3x120 deg.) for control of energy deposition in angle and along the device length in order to satisfy anatomical constraints. The device is housed in a 6 mm diameter PET catheter with cooling water flow for endocervical implantation. Devices were characterized by measuring acoustic efficiencies, rotational acoustic intensity distributions, and rotational temperature distributions in phantom. Results: The CTV in HDR brachytherapy plans extends 20.5{+-}5.0 mm from the endocervical tandem with the rectum and bladder typically <8 mm from the target boundary. The GTV extends 19.4{+-}7.3 mm from the tandem. Simulations indicate that for 60

  9. Motility Related Actinin Alpha-4 Is Associated with Advanced and Metastatic Ovarian Carcinoma

    PubMed Central

    Barbolina, Maria V.; Adley, Brian P.; Kelly, David L.; Fought, Angela J.; Scholtens, Denise; Shea, Lonnie D.; Sharon Stack, M.

    2010-01-01

    Advanced and metastatic ovarian cancer is a leading cause of death from gynecologic malignancies. A more detailed understanding of the factors controlling invasion and metastasis may lead to novel anti-metastatic therapies. To model cellular interactions that occur during intraperitoneal metastasis, comparative cDNA microarray analysis and confirmatory real time RT-PCR were employed to uncover changes in gene expression that may occur in late stage ovarian cancer in response to microenvironmental cues, particularly native three-dimensional collagen I. Gene expression in human ovarian carcinoma tissues was evaluated on the RNA and protein level using real time RT-PCR and immunohistochemistry. Cell invasion and migration were evaluated in a collagen invasion assay and a scratch wound assay. Three-dimensional collagen I culture led to differential expression of several genes. The role of actinin alpha-4 (ACTN4), a cytosketeton-associated protein implicated in regulation of cell motility, was examined in detail. ACTN4 RNA and protein expression were associated with advanced and metastatic human ovarian carcinoma. This report demonstrates that a cytoskeletal-associated protein ACTN4 is upregulated by three-dimensional collagen culture conditions, leading to increased invasion and motility of ovarian cancer cells. Expression of ACTN4 in human ovarian tumors was found to be associated with advanced stage disease and peritoneal metastases. PMID:18362906

  10. Sneddon-Wilkinson disease induced by sorafenib in a patient with advanced hepatocellular carcinoma.

    PubMed

    Tajiri, Kazuto; Nakajima, Takahiko; Kawai, Kengo; Minemura, Masami; Sugiyama, Toshiro

    2015-01-01

    Sorafenib is the standard treatment for patients with advanced hepatocellular carcinoma (HCC), although it is known to cause a variety of dermatologic adverse events. Subcorneal pustular dermatosis (SCPD), also known as Sneddon-Wilkinson disease, is a rare skin eruption that accompanies various systemic disorders and may become chronically progressive. We herein describe the case of a patient who developed SCPD after sorafenib administration. The dermatologic reaction was improved by the cessation of sorafenib and worsened by its readministration. Clinicians treating HCC patients with sorafenib should be aware of the possibility of SCPD. PMID:25786448

  11. Evaluation of antiangiogenic efficacy in advanced hepatocellular carcinoma: Biomarkers and functional imaging

    PubMed Central

    Bouattour, Mohamed; Payancé, Audrey; Wassermann, Johanna

    2015-01-01

    Many years after therapeutic wilderness, sorafenib finally showed a clinical benefit in patients with advanced hepatocellular carcinoma. After the primary general enthusiasm worldwide, some disappointments emerged particularly since no new treatment could exceed or at least match sorafenib in this setting. Without these new drugs, research focused on optimizing care of patients treated with sorafenib. One challenging research approach deals with identifying prognostic and predictive biomarkers of sorafenib in this population. The task still seems difficult; however appropriate investigations could resolve this dilemma, as observed for some malignancies where other drugs were used. PMID:26380650

  12. Immunological Treatment Options for Locoregionally Advanced Head and Neck Squamous Cell Carcinoma

    PubMed Central

    Mirandola, Leonardo; Bernardini, Giovanni; Cunha, Nicholas D’; Tijani, Lukman; Nguyen, Diane; Cordero, Joehassin; Jenkins, Marjorie R.; Cobos, Everardo; Kast, W. Martin; Chiriva-Internati, Maurizio

    2014-01-01

    Patients with squamous cell carcinoma of the head and neck (HNSCC) are usually treated by a multimodal approach with surgery and/or radiochemotherapy as the mainstay of local–regional treatment in cases with advanced disease. Both chemotherapy and radiation therapy have the disadvantage of causing severe side effects, while the clinical outcome of patients diagnosed with HNSCC has remained essentially unchanged over the last decade. The potential of immunotherapy is still largely unexplored. Here the authors review the current status of the art and discuss the future challenges in HNSCC treatment and prevention. PMID:22251006

  13. Sneddon-Wilkinson disease induced by sorafenib in a patient with advanced hepatocellular carcinoma.

    PubMed

    Tajiri, Kazuto; Nakajima, Takahiko; Kawai, Kengo; Minemura, Masami; Sugiyama, Toshiro

    2015-01-01

    Sorafenib is the standard treatment for patients with advanced hepatocellular carcinoma (HCC), although it is known to cause a variety of dermatologic adverse events. Subcorneal pustular dermatosis (SCPD), also known as Sneddon-Wilkinson disease, is a rare skin eruption that accompanies various systemic disorders and may become chronically progressive. We herein describe the case of a patient who developed SCPD after sorafenib administration. The dermatologic reaction was improved by the cessation of sorafenib and worsened by its readministration. Clinicians treating HCC patients with sorafenib should be aware of the possibility of SCPD.

  14. Cixutumumab, Everolimus, and Octreotide Acetate in Treating Patients With Advanced Low to Intermediate Grade Neuroendocrine Carcinoma

    ClinicalTrials.gov

    2016-07-14

    Gastrin-Producing Neuroendocrine Tumor; Lung Carcinoid Tumor; Metastatic Digestive System Neuroendocrine Tumor G1; Pancreatic Glucagonoma; Pancreatic Insulinoma; Pancreatic Polypeptide Tumor; Paraganglioma; Recurrent Digestive System Neuroendocrine Tumor G1; Recurrent Merkel Cell Carcinoma; Recurrent Pancreatic Neuroendocrine Carcinoma; Regional Digestive System Neuroendocrine Tumor G1; Somatostatin-Producing Neuroendocrine Tumor; Stage III Merkel Cell Carcinoma; Stage IV Merkel Cell Carcinoma; Thyroid Gland Medullary Carcinoma

  15. PD-1 Blockade with Pembrolizumab in Advanced Merkel-Cell Carcinoma

    PubMed Central

    Nghiem, Paul T.; Bhatia, Shailender; Lipson, Evan J.; Kudchadkar, Ragini R.; Miller, Natalie J.; Annamalai, Lakshmanan; Berry, Sneha; Chartash, Elliot K.; Daud, Adil; Fling, Steven P.; Friedlander, Philip A.; Kluger, Harriet M.; Kohrt, Holbrook E.; Lundgren, Lisa; Margolin, Kim; Mitchell, Alan; Olencki, Thomas; Pardoll, Drew M.; Reddy, Sunil A.; Shantha, Erica M.; Sharfman, William H.; Sharon, Elad; Shemanski, Lynn R.; Shinohara, Michi M.; Sunshine, Joel C.; Taube, Janis M.; Thompson, John A.; Townson, Steven M.; Yearley, Jennifer H.; Topalian, Suzanne L.; Cheever, Martin A.

    2016-01-01

    BACKGROUND Merkel-cell carcinoma is an aggressive skin cancer that is linked to exposure to ultraviolet light and the Merkel-cell polyomavirus (MCPyV). Advanced Merkel-cell carcinoma often responds to chemotherapy, but responses are transient. Blocking the programmed death 1 (PD-1) immune inhibitory pathway is of interest, because these tumors often express PD-L1, and MCPyV-specific T cells express PD-1. METHODS In this multicenter, phase 2, noncontrolled study, we assigned adults with advanced Merkel-cell carcinoma who had received no previous systemic therapy to receive pembrolizumab (anti–PD-1) at a dose of 2 mg per kilogram of body weight every 3 weeks. The primary end point was the objective response rate according to Response Evaluation Criteria in Solid Tumors, version 1.1. Efficacy was correlated with tumor viral status, as assessed by serologic and immunohistochemical testing. RESULTS A total of 26 patients received at least one dose of pembrolizumab. The objective response rate among the 25 patients with at least one evaluation during treatment was 56% (95% confidence interval [CI], 35 to 76); 4 patients had a complete response, and 10 had a partial response. With a median follow-up of 33 weeks (range, 7 to 53), relapses occurred in 2 of the 14 patients who had had a response (14%). The response duration ranged from at least 2.2 months to at least 9.7 months. The rate of progression-free survival at 6 months was 67% (95% CI, 49 to 86). A total of 17 of the 26 patients (65%) had virus-positive tumors. The response rate was 62% among patients with MCPyV-positive tumors (10 of 16 patients) and 44% among those with virus-negative tumors (4 of 9 patients). Drug-related grade 3 or 4 adverse events occurred in 15% of the patients. CONCLUSIONS In this study, first-line therapy with pembrolizumab in patients with advanced Merkel-cell carcinoma was associated with an objective response rate of 56%. Responses were observed in patients with virus-positive tumors

  16. Salivary biomarkers for detection of oral squamous cell carcinoma – current state and recent advances

    PubMed Central

    Yakob, Maha; Fuentes, Laurel; Wang, Marilene B.; Abemayor, Elliot; Wong, David T.W.

    2014-01-01

    Oral squamous cell carcinoma (OSCC) is the most common malignant neoplasm of the oral cavity. Detection of OSCC is currently based on thorough clinical oral examination combined with biopsy for histological analysis. Most cases of OSCC are not detected until the cancer has developed into advanced stages; thus, a reliable early stage diagnostic marker is needed. This literature review presents an overview of the status of current advances in salivary diagnostics for OSCC. Though many protein and mRNA salivary biomarkers have been identified that can detect OSCC with high sensitivity and specificity, the most discernable findings occur with the use of multiple markers. Studies that incorporate proteomic, transcriptomic, and potentially additional “omics”, including methylomics, need to be initiated to bring technology to clinical applications and allow the best use of saliva in diagnosing OSCC. PMID:24883261

  17. Percutaneous Irreversible Electroporation of Locally Advanced Pancreatic Carcinoma Using the Dorsal Approach: A Case Report

    SciTech Connect

    Scheffer, Hester J. Melenhorst, Marleen C. A. M.; Vogel, Jantien A.; Tilborg, Aukje A. J. M. van; Nielsen, Karin Kazemier, Geert; Meijerink, Martijn R.

    2015-06-15

    Irreversible electroporation (IRE) is a novel image-guided ablation technique that is increasingly used to treat locally advanced pancreatic carcinoma (LAPC). We describe a 67-year-old male patient with a 5 cm stage III pancreatic tumor who was referred for IRE. Because the ventral approach for electrode placement was considered dangerous due to vicinity of the tumor to collateral vessels and duodenum, the dorsal approach was chosen. Under CT-guidance, six electrodes were advanced in the tumor, approaching paravertebrally alongside the aorta and inferior vena cava. Ablation was performed without complications. This case describes that when ventral electrode placement for pancreatic IRE is impaired, the dorsal approach could be considered alternatively.

  18. Sorafenib for the treatment of advanced hepatocellular carcinoma with extrahepatic metastasis: a prospective multicenter cohort study.

    PubMed

    Nakano, Masahito; Tanaka, Masatoshi; Kuromatsu, Ryoko; Nagamatsu, Hiroaki; Tajiri, Nobuyoshi; Satani, Manabu; Niizeki, Takashi; Aino, Hajime; Okamura, Shusuke; Iwamoto, Hideki; Shimose, Shigeo; Shirono, Tomotake; Koga, Hironori; Torimura, Takuji

    2015-12-01

    Sorafenib, an oral multikinase inhibitor, is approved for advanced hepatocellular carcinoma (HCC) treatment. However, its therapeutic effect in advanced HCC patients with extrahepatic metastasis remains uncertain. This study aimed to prospectively assess the efficacy, safety, and survival risk factors and evaluate the prognostic impact of sorafenib treatment in advanced HCC patients with or without extrahepatic metastasis. Between May 2009 and March 2014, 312 consecutive advanced HCC patients who received sorafenib were enrolled in this study. We evaluated their characteristics and compared the clinical outcomes of those with and without extrahepatic metastasis. Of the enrolled patients, 245 (81%) received sorafenib treatment for more than 1 month, with a median duration of 3.6 months. Eighteen patients demonstrated partial response to sorafenib therapy, 127 had stable disease, and 134 had progressive disease at the first radiologic assessment. The median survival time (MST) and progression-free survival (PFS) were 10.3 and 3.6 months, respectively. Multivariate analysis identified gender, Child-Pugh class, baseline serum des-gamma-carboxy prothrombin level, and treatment duration as independent risk factors for survival. Extrahepatic metastasis was detected in 178 patients. However, the MST, PFS, and therapeutic effect were comparable between patients with and without extrahepatic metastasis. The independent risk factors for decreased overall survival in patients with extrahepatic metastasis were similar to those affecting all patients. Our results indicated that sorafenib could be administered for hepatic reserve and as long-term treatment for advanced HCC patients regardless of their extrahepatic metastasis status.

  19. The effect of locoregional therapies in patients with advanced hepatocellular carcinoma treated with sorafenib

    PubMed Central

    Sarpel, Umut; Spivack, John H.; Berger, Yaniv; Heskel, Marina; Aycart, Samantha N.; Sweeney, Robert; Edwards, Martin P.; Labow, Daniel M.; Kim, Edward

    2016-01-01

    Background & aims It is unknown whether the addition of locoregional therapies (LRTx) to sorafenib improves prognosis over sorafenib alone in patients with advanced hepatocellular carcinoma (HCC). The aim of this study was to assess the effect of LRTx in this population. Methods A retrospective analysis was performed of patients with advanced HCC as defined by extrahepatic metastasis, lymphadenopathy >2 cm, or gross vascular invasion. Sorafenib therapy was required for inclusion. Survival of patients who received LRTx after progression to advanced stage was compared to those who did not receive LRTx. Results Using an intention to treat analysis of 312 eligible patients, a propensity weighted proportional hazards model demonstrated LRTx as a predictor of survival (HR = 0.505, 95% CI: 0.407–0.628; P < 0.001). The greatest benefit was seen in patients with the largest tumor burden (HR = 0.305, 95% CI: 0.236–0.393; P < 0.01). Median survival in the sorafenib arm was 143 days (95% CI: 118–161) vs. 247 days (95% CI: 220–289) in the sorafenib plus LRTx arm (P < 0.001). Conclusions These results demonstrate a survival benefit with the addition of LRTx to sorafenib for patients with advanced HCC. These findings should prompt a prospective clinical trial to further assess the role of LRTx in patients with advanced HCC. PMID:27154804

  20. Planned preoperative radiation therapy for advanced laryngeal carcinoma. [/sup 60/Co

    SciTech Connect

    Kazem, I.; van den Broek, P.; Huygen, P.L.M.

    1982-09-01

    One hundred ten patients with predominantly advanced laryngeal carcinoma were treated in the period 1969-1978 with planned preoperative radiation therapy followed by surgery. Site distribution was: 63 supraglottic, 26 glottic, 15 transglottic and 6 subglottic. There were 4 Stage II patients, 66 Stage III and 40 Stage IV. Preoperative radiation therapy consisted of Telecobalt irradiation to a total dose of 25 Gy given to a target volume encompassing the larynx and regional neck nodes, given in 5 equal daily fractions of 5 Gy in 5 consecutive days. Surgery was performed 2 days later. Total laryngectomy was performed on 48 patients, total laryngectomy with neck dissection on 55 patients, supraglottic laryngectomy on 5 and supraglottic laryngectomy with neck dissection on 2 patients. Crude actuarial 5 and 10 year survival probability for the whole group is 71 and 61%, respectively. The corrected 5 and 10 year survival is 75%. For patients with T/sub 3/-T/sub 4/-N/sub 0/ tumors 5 and 10 year survival probability is: crude 65 and 58%, and corrected 70% respectively. For T/sub 3/-T/sub 4/-N/sub +/ crude: 75 and 60% and corrected: 78%. Of 110 patients, one died postoperative, three died of intercurrent disease, five died as a result of second malignancy, and 23 died of their larynx carcinoma: 12/23 because of locoregional failure, and 11/23 because of distant metastasis. We concluded that short intensive preoperative radiation therapy and surgery offer a high cure rate in the treatment of advanced resectable laryngeal carcinoma. The merits of this technique are outlined in the text.

  1. Malignant peripheral nerve sheet tumour of cervix.

    PubMed

    Akhavan, Ali; Moghimi, Mansour; Karimi-Zarchi, Mojgan; Navabii, Hossein

    2012-05-30

    Sarcomas account for less than 1% of malignancies of the uterine cervix. Among them, rhabdomyosarcomas are the ones most frequently reported. Malignant peripheral nerve sheet tumour (MPNST) is very rare. In this paper we present a 53-year-old woman with MPNST of the uterine cervix.

  2. Magnetic resonance imaging and positron-emission tomography imaging in the 21st century as tools for the evaluation and management of patients with invasive cervical carcinoma.

    PubMed

    Wolfson, Aaron H

    2006-07-01

    For over 4 decades, the delivery of definitive radiotherapy to patients with carcinoma of the cervix has involved both external beam and brachytherapy. Both of these therapeutic modalities have been traditionally linked to 2-dimensional radiographic guidance. Currently, the staging of these tumors still resides in clinical examinations and 2-dimensional diagnostic x-rays. Recently, there have been significant technological developments in imaging, namely magnetic resonance imaging and positron-emission tomography. These novel radiologic advances have subsequently led to a number of investigational studies, which in turn have shown a "paradigm shift" not only in the diagnosis but also in the radiation delivery used for patients with invasive carcinoma of the cervix.

  3. Endocervicosis of the Uterine Cervix.

    PubMed

    Mobarki, Mousa; Karpathiou, Georgia; Forest, Fabien; Corsini, Thomas; Peoc'h, Michel

    2016-09-01

    Endocervicosis is considered a form of Mülleriosis affecting mainly the bladder and is comprised of endocervical-type glands and cysts. It has been rarely described in the uterine cervix where the extensive involvement of cervical and paracervical tissue poses the suspicion of malignancy, mostly minimal-deviation adenocarcinoma. We describe a case of cervical endocervicosis causing long-term symptoms leading to hysterectomy. We provide evidence that this pathology is associated with cesarean section similar with isthmocele. Its differential diagnosis is discussed. PMID:26825004

  4. Advanced basal cell carcinoma, the hedgehog pathway, and treatment options – role of smoothened inhibitors

    PubMed Central

    Fecher, Leslie A; Sharfman, William H

    2015-01-01

    Cutaneous basal cell carcinoma (BCC) is the most common human cancer and its incidence is rising worldwide. Ultraviolet radiation exposure, including tanning bed use, as well as host factors play a role in its development. The majority of cases are treated and cured with local therapies including surgery. Yet, the health care costs of diagnosis and treatment of BCCs in the US is substantial. In the United States, the cost of nonmelanoma skin cancer care in the Medicare population is estimated to be US$426 million per year. While rare, locally advanced BCCs that can no longer be controlled with surgery and/or radiation, and metastatic BCCs do occur and can be associated with significant morbidity and mortality. Vismodegib (GDC-0449), a smoothened inhibitor targeted at the hedgehog pathway, is the first US Food and Drug Association (FDA)-approved agent in the treatment of locally advanced, unresectable, and metastatic BCCs. This class of agents appears to be changing the survival rates in advanced BCC patients, but appropriate patient selection and monitoring are important. Multidisciplinary assessments are essential for the optimal care and management of these patients. For some patients with locally advanced BCC, treatment with a hedgehog inhibitor may eliminate the need for an excessively disfiguring or morbid surgery. PMID:26604681

  5. [Transarterial infusion chemotherapy using fine-powder cisplatin in patients with advanced hepatocellular carcinoma].

    PubMed

    Hatanaka, Takeshi; Kakizaki, Satoru; Ueno, Takashi; Takeuchi, Suguru; Takizawa, Daichi; Katakai, Kenji

    2014-02-01

    We investigated the therapeutic effects and safety of fine powder cisplatin for patients with advanced hepatocellular carcinoma( HCC). From January 2006 to March 2012, 123 patients with advanced HCC were treated by transarterial infusion chemotherapy(TAI)with fine-powder cisplatin(IA-call®, Nippon Kayaku Co. Ltd., Tokyo, Japan). The drug was infused into the liver through the feeding artery at a dose of 65 mg/m2. The treatment was repeated every 4 to 8 weeks until evidence of either tumor progression or unacceptable toxicity appeared. Treatment responses were classified as complete response(CR), partial response(PR), stable disease(SD), and progressive disease(PD)in 3.2%, 12.0%, 32.2%, and 52.4% of patients, respectively. The median survival durations were as follows: overall, 12.2 months; CR/PR patients, 23.8 months; and SD/PD patients, 10.6 months. The cumulative survival rates of CR/PR patients were significantly higher than those of SD/PD patients (p<0.05). Multivariate analyses revealed that treatment response, etiology, Child-Pugh grading, and level of protein induced by the vitamin K antagonist- II (PIVKA- II )were predictive factors of survival duration. Problematic adverse events were not observed in any of the patients. Our results suggest that TAI using fine-powder cisplatin can be safely administered for advanced HCC and can improve the prognosis of patients with advanced disease. PMID:24743198

  6. Neoadjuvant chemoradiotherapy followed by surgery in locally advanced squamous cell carcinoma of the vulva

    PubMed Central

    GAUDINEAU, A.; WEITBRUCH, D.; QUETIN, P.; HEYMANN, S.; PETIT, T.; VOLKMAR, P.; BODIN, F.; VELTEN, M.; RODIER, J.F.

    2012-01-01

    Alternative therapies have been sought to alleviate mutilation and morbidity associated with surgery for vulvar neoplasms. Our prime objective was to assess tumor absence in pathological vulvar and nodal specimens following neoadjuvant chemoradiotherapy in locally advanced vulvar neoplasms. Data were retrospectively collected from January 2001 to May 2009 from 22 patients treated with neoadjuvant therapy for locally advanced squamous cell carcinoma of the vulva. Neoadjuvant treatment consisted of inguino-pelvic radiotherapy (50 Gy) in association with chemotherapy when possible. Surgery occurred at intervals of between 5 to 8 weeks. The median age of patients at diagnosis was 74.1 years. All patients were primarily treated with radiotherapy and 15 received a concomitant chemotherapy. Additionally, all patients underwent radical vulvectomy and bilateral inguino-femoral lymphadenectomy. Tumor absence in the vulvar and nodal pathological specimens was achieved for 6 (27%) patients, while absence in the vulvar pathological specimens was only achieved for 10 (45.4%) patients. Postoperative follow-up revealed breakdown of groin wounds, vulvar wounds and chronic lymphedema in 3 (14.3%), 7 (31.8%) and 14 cases (63.6%), respectively. Within a median follow-up time of 2.3 years [interquartile range (IQR), 0.6–4.6], 12 (54.6%) patients experienced complete remission and 6 cases succumbed to metastatic evolution within a median of 2.2 years (IQR, 0.6–4.6), with 1 case also experiencing perineal recurrence. Median survival time, estimated using the Kaplan-Meier method, was 5.1 years (IQR, 1.0–6.8). We suggest that neoadjuvant chemoradiotherapy may represent a reliable and promising strategy in locally advanced squamous cell carcinoma of the vulva. PMID:23205089

  7. Adjuvant radiotherapy after transoral laser microsurgery for advanced squamous carcinoma of the head and neck

    SciTech Connect

    Pradier, Olivier . E-mail: opradier@gwdg.de; Christiansen, Hans; Schmidberger, Heinz; Martin, Alexios; Jaeckel, Martin C.; Steiner, Wolfgang; Ambrosch, Petra; Kahler, Elke; Hess, Clemens F.

    2005-12-01

    Purpose: To evaluate the efficacy of an adjuvant radiotherapy after transoral laser microsurgery for advanced squamous cell carcinoma of the head and neck and to show that a less invasive surgery with organ preservation in combination with radiotherapy is an alternative to a radical treatment. Patients and Methods: Between 1987 and 2000, 208 patients with advanced squamous cell carcinoma of the head and neck were treated with postoperative radiotherapy after surgical CO{sub 2} laser resection. Primary sites included oral cavity, 38; oropharynx, 88; larynx, 36; hypopharynx, 46. Disease stages were as follows: Stage III, 40 patients; Stage IV, 168 patients. Before 1994, the treatment consisted of a split-course radiotherapy with carboplatinum (Treatment A). After 1994, the patients received a conventional radiotherapy (Treatment B). Results: Patients had 5-year locoregional control and disease-specific survival (DSS) rates of 68% and 48%, respectively. The 5-year DSS was 70% and 44% for Stages III and IV, respectively (p = 0.00127). Patients treated with a hemoglobin level greater or equal to 13.5 g/dL before radiotherapy had a 5-year DSS of 55% as compared with 39% for patients treated with a hemoglobin level greater than 13.5 g/dL (p = 0.0054). Conclusion: In this series of patients with advanced head-and-neck tumors, transoral laser surgery in combination with adjuvant radiotherapy resulted in locoregional control and DSS rates similar to those reported for radical surgery followed by radiotherapy. Treatment B has clearly been superior to Treatment A. A further improvement of our treatment regimen might be expected by the combination of adjuvant radiotherapy with concomitant platinum-based chemotherapy.

  8. Management of inferior vena cava tumor thrombus in locally advanced renal cell carcinoma

    PubMed Central

    Psutka, Sarah P.

    2015-01-01

    The diagnosis of renal cell carcinoma is accompanied by intravascular tumor thrombus in up to 10% of cases, of which nearly one-third of patients also have concurrent metastatic disease. Surgical resection in the form of radical nephrectomy and caval thrombectomy represents the only option to obtain local control of the disease and is associated with durable oncologic control in approximately half of these patients. The objective of this clinical review is to outline the preoperative evaluation for, and operative management of patients with locally advanced renal cell carcinoma with venous tumor thrombi involving the inferior vena cava. Cornerstones of the management of these complex patients include obtaining high-quality imaging to characterize the renal mass and tumor thrombus preoperatively, with further intraoperative real-time evaluation using transesophageal echocardiography, careful surgical planning, and a multidisciplinary approach. Operative management of patients with high-level caval thrombi should be undertaken in high-volume centers by surgical teams with capacity for bypass and invasive intraoperative monitoring. In patients with metastatic disease at presentation, cytoreductive nephrectomy and tumor thrombectomy may be safely performed with simultaneous metastasectomy if possible. In the absence of level one evidence, neoadjuvant targeted therapy should continue to be viewed as experimental and should be employed under the auspices of a clinical trial. However, in patients with significant risk factors for postoperative complications and mortality, and especially in those with metastatic disease, consultation with medical oncology and frontline targeted therapy may be considered. PMID:26445601

  9. Atypical culture-negative skull base osteomyelitis masquerading as advanced nasopharyngeal carcinoma.

    PubMed

    See, Anna; Tan, Tiong Yong; Gan, Eng Cern

    2016-01-01

    Skull base osteomyelitis typically arises as a complication of otogenic or sinonasal infections in immunocompromised patients. A much rarer entity, atypical skull base osteomyelitis is not associated with an obvious infective source. Atypical and culture-negative skull base osteomyelitis is even rarer and hampers diagnosis, as its clinical presentation is remarkably similar to skull base neoplasms. We report a case of extensive skull base osteomyelitis with orbital apex syndrome and multiple lower cranial nerve palsies which initially masqueraded as possible advanced nasopharyngeal carcinoma. Extensive investigations and consult with an infectious diseases specialist aided in elucidation of the correct diagnosis. Through this article, we emphasize that skull base osteomyelitis must be considered in the setting of headache, cranial neuropathies, elevated inflammatory markers and abnormal imaging findings. Early tissue sampling for histology, stainings and cultures and prompt appropriate treatment may prevent or arrest further complications. PMID:27178515

  10. Rapid sequence treatment of advanced squamous cell carcinoma of the upper aerodigestive tract: A pilot study

    SciTech Connect

    Moloy, P.J.; Moran, E.M.; Azawi, S. )

    1991-01-01

    A review of the literature suggested that prolonged treatment time may lessen the probability of cure for patients with advanced squamous cell carcinoma of the upper aerodigestive tract. To shorten treatment time, rapid sequence treatment (RST) was devised in which chemotherapy, surgery, and irradation were administered in a total treatment time of 8 weeks. Twelve patients were treated and followed 3 years or longer. Medical complications were minor. Osteonecrosis occurred in each of the first five patients and was the only major complication of the protocol. Surgical techniques were modified, and no additional patient developed osteonecrosis. No patient developed local or regional recurrence. Two patients developed distant metastases and three other patients developed second primaries. Absolute survival was 50%. Rapid sequence treatment is an aggressive and potentially hazardous protocol that yielded encouraging results in this pilot study.

  11. Acute chylous peritonitis mimicking ovarian torsion in a patient with advanced gastric carcinoma.

    PubMed

    Kang, Chang Moo; Kim, Sunghoon; Kim, Bub Woo; Kim, Kyung Sik; Choi, Jin Sub; Lee, Woo Jung; Kim, Byong Ro

    2007-09-01

    The extravasation of chyle into the peritoneal space usually does not accompany an abrupt onset of abdominal pain with symptoms and signs of peritonitis. The rarity of this condition fails to reach preoperative diagnosis prior to laparotomy. Here, we introduce a case of chylous ascites that presented with acute abdominal pain mimicking peritonitis caused by ovarian torsion in a 41-yr-old female patient with advanced gastric carcinoma. An emergency exploratory laparotomy was performed but revealed no evidence of ovarian torsion. Only chylous ascites was discovered in the operative field. She underwent a complete abdominal hysterectomy and salphingo-oophorectomy. Only saline irrigation and suction-up were performed for the chylous ascites. The postoperative course was uneventful. Her bowel movement was restored within 1 week. She was allowed only a fat-free diet, and no evidence of re-occurrence of ascites was noted on clinical observation. She now remains under consideration for additional chemotherapy.

  12. Vismodegib: A smoothened inhibitor for the treatment of advanced basal cell carcinoma.

    PubMed

    Aditya, Suruchi; Rattan, Aditya

    2013-10-01

    Incidence of basal cell carcinoma (BCC), the most common skin cancer in humans, is rising. Surgery is the mainstay of treatment but there is no standard of care for locally advanced or metastatic disease. Hedgehog signaling proteins are critical for cell growth and differentiation during embryogenesis; Hh pathway is silenced in adults. Dysregulated or aberrant Hh signaling has been implicated in the pathogenesis of BCC. This hyperactive pathway can be inhibited by use of smoothened inhibitors such as vismodegib. Food and drug administration approved this oral, once-daily medication in 2012 to treat adults with metastatic BCC or locally advanced, recurrent BCC after surgery and also for patients with locally advanced BCC who are not candidates for surgery or radiation treatment. Clinical studies have shown it to be highly efficacious and the most common adverse effects include, muscle spasms, alopecia and dysgeusia. Use of targeted biologic modifiers, exemplified by Hh directed therapeutics offer a new hope to patients with high-surgical morbidity or inoperable tumors.

  13. Sorafenib-induced acute interstitial pneumonia in patients with advanced hepatocellular carcinoma: report of three cases.

    PubMed

    Takeda, Haruhiko; Nishikawa, Hiroki; Iguchi, Eriko; Matsuda, Fumihiro; Kita, Ryuichi; Kimura, Toru; Osaki, Yukio

    2012-01-01

    Little is known about acute interstitial pneumonia (AIP) induced by sorafenib therapy in patients with advanced hepatocellular carcinoma (HCC). Here, we present three patients with advanced HCC who developed AIP during sorafenib therapy, with fatal complications in two cases. Case 1 was a 76-year-old man who developed dyspnea. Chest CT showed interstitial pneumonia. Sorafenib was discontinued immediately, and prednisolone was started. His pneumonia resolved. A drug-induced lymphocyte stimulation test for sorafenib was positive. Case 2 was a 75-year-old man and case 3 was a 77-year-old man, both of whom developed high-grade fever and hypoxemia during sorafenib therapy, and were diagnosed with AIP. In spite of high-dose steroid therapy, their respiratory failure worsened and both patients died. In all three cases, serum KL-6 or surfactant protein D concentrations were elevated, and blood and sputum cultures did not grow pathogens. All three patients were smokers with restrictive lung disease on preoperative respiratory function testing, but did not have respiratory symptoms before sorafenib therapy. The clinical features of these three cases suggest that male gender, older age, smoking history, and lung disease are associated with acute sorafenib-induced AIP in patients with advanced HCC.

  14. Chemotherapy and target therapy for hepatocellular carcinoma: New advances and challenges

    PubMed Central

    Deng, Gan-Lu; Zeng, Shan; Shen, Hong

    2015-01-01

    Primary liver cancer is one of the commonest causes of death. Hepatocellular carcinoma (HCC) accounts for 90% of primary liver cancers. For patients with unresectable or metastatic HCC, conventional chemotherapy is of limited or no benefit. Sorafenib is the only systemic treatment to demonstrate a statistically significant but modest overall survival benefit, leading to an era of targeted agents. Many clinical trials of targeted drugs have been carried out with many more in progress. Some drugs like PTK787 showed potential benefits in the treatment of HCC. Despite these promising breakthroughs, patients with HCC still have a dismal prognosis. Recently, both a phase III trial of everolimus and a phase II clinical trial of trebananib failed to demonstrate effective antitumor activity in advanced HCC. Sorafenib still plays a pivotal role in advanced HCC, leading to further explorations to exert its maximum efficacy. Combinations targeted with chemotherapy or transarterial chemoembolization is now being tested and might bring about advances. New targeted agents such as mammalian target of rapamycin inhibitors are under investigation, as well as further exploration of the mechanism of hepatocarcinogenesis. PMID:25914779

  15. Patterns of treatment and costs of intermediate and advanced hepatocellular carcinoma management in four Italian centers

    PubMed Central

    Colombo, Giorgio Lorenzo; Cammà, Calogero; Attili, Adolfo Francesco; Ganga, Roberto; Gaeta, Giovanni Battista; Brancaccio, Giuseppina; Franzini, Jean Marie; Volpe, Marco; Turchetti, Giuseppe

    2015-01-01

    Background Hepatocellular carcinoma (HCC) is a severe health condition associated with high hospitalizations and mortality rates, which also imposes a relevant economic burden. Purpose The aim of the present survey is to investigate treatment strategies and related costs for HCC in the intermediate and advanced stages of the disease. Patients and methods The survey was conducted in four Italian centers through structured interviews with physicians. Information regarding the stage of disease, treatments performed, and related health care resource consumption was included in the questionnaire. Direct health care cost per patient associated with the most relevant treatments such as sorafenib, transarterial chemoembolization (TACE), and transarterial radioembolization (TARE) was evaluated. Results Between 2013 and 2014, 285 patients with HCC were treated in the four participating centers; of these, 80 were in intermediate stage HCC (Barcelona Clinic Liver Cancer Classification [BCLC] B), and 57 were in the advanced stage of the disease (BCLC C). In intermediate stage HCC, the most frequent first-line treatment was TACE (63%) followed by sorafenib (15%), radiofrequency ablation (14%), and TARE (1.3%). In the advanced stage of HCC, the most frequently used first-line therapy was sorafenib (56%), followed by best supportive care (21%), TACE (18%), and TARE (3.5%). The total costs of treatment per patient amounted to €12,214.54 with sorafenib, €13,418.49 with TACE, and €26,106.08 with TARE. Both in the intermediate and in the advanced stage of the disease, variability in treatment patterns among centers was observed. Conclusion The present analysis raises for the first time the awareness of the overall costs incurred by the Italian National Healthcare System for different treatments used in intermediate and advanced HCC. Further investigations would be important to better understand the effective health care resource usage. PMID:26527877

  16. LYMPHOPENIA AS A PROGNOSTIC FACTOR FOR OVERALL SURVIVAL IN ADVANCED CARCINOMAS, SARCOMAS AND LYMPHOMAS

    PubMed Central

    Ray-Coquard, Isabelle; Cropet, Claire; Van Glabbeke, Martine; Sebban, Catherine; Le Cesne, Axel; Judson, Ian; Tredan, Olivier; Verweij, Jaap; Biron, Pierre; Labidi, Inthidar; Guastalla, Jean-Paul; Bachelot, Thomas; Perol, David; Chabaud, Sylvie; Hogendoorn, Pancras C.W.; Cassier, Philippe; Dufresne, Armelle; Blay, Jean-Yves

    2009-01-01

    Lymphopenia is frequent in advanced cancers and predicts the toxicity of chemotherapy. Its impact on relapse and survival is uncertain. Its prognostic value for survival was analyzed in 3 databases of previously reported prospective multicenter studies: 1) FEC chemotherapy in metastatic breast carcinoma; 2) CYVADIC in advanced soft-tissue sarcoma (EORTC-STBSG 62791); 3) prospective, consecutive phase III studies of aggressive diffuse large-cell non-Hodgkin’s lymphomas conducted at Bérard center between 1987 and 1993. Univariate and multivariate analyses of prognostic factors for survival were performed. The incidence of lymphopenia <1000/μL before treatment was constant among series: 25%, 24%, 27% respectively. Lymphopenia was significantly more frequent (p<0.05) in metastatic breast cancer patients with performance status (PS)>1, non-Hodgkin’s lymphoma patients with international prognostic index (IPI)>0, and advanced soft-tissue sarcoma and metastatic breast cancer patients with bone metastases. In univariate analysis, lymphopenia <1000/μL significantly correlated to overall survival in patients with metastatic breast cancer (median 10 vs. 14 months, p <0.0001), advanced soft-tissue sarcoma (median 5 vs. 10 months, p <0.01), and non-Hodgkin lymphoma (median 11 vs. 94 months, p <0.0001). In multivariate analysis (Cox model), lymphopenia was an independent prognostic factor for overall survival in metastatic breast cancer (RR: 1.8; 95%CI 1.3–2.4) along with liver metastases and PS; in advanced soft-tissue sarcoma (RR: 1.46; 95%CI 1.0–2.1) along with liver metastases, lung metastases and PS; and in non-Hodgkin’s lymphoma (RR: 1.48; 95%CI 1.03–2.1) along with IPI. Our findings demonstrate that lymphopenia is an independent prognostic factor for overall and progression-free survival in several cancers. PMID:19549917

  17. [Preinvasive lesions in gynaecology - uterine cervix].

    PubMed

    Mouková, L; Feranec, R; Chovanec, J

    2013-01-01

    Preinvasive lesion of the uterine cervix can give rise to cervical cancer. High-risk human papillomaviruses with high oncogenic potential are considered to be the main etiopathological factors with interaction of other risk factors (recurrent inflammation of the cervix, injury of the cervix, immunosuppressive conditions, sexual promiscuity, etc.). Early dia-gnosis of these changes at regular gynecological examinations and adequate treatment can prevent of malignant transformation. Organized cervical screening and implementation of nationwide vaccination against human papillomavirus promises to reduce the incidence of cervical cancer. PMID:24325165

  18. The usefulness of an independent patient-specific treatment planning verification method using a benchmark plan in high-dose-rate intracavitary brachytherapy for carcinoma of the uterine cervix.

    PubMed

    Takahashi, Yutaka; Koizumi, Masahiko; Sumida, Iori; Isohashi, Fumiaki; Ogata, Toshiyuki; Akino, Yuichi; Yoshioka, Yasuo; Maruoka, Shintaro; Inoue, Shinichi; Konishi, Koji; Ogawa, Kazuhiko

    2012-11-01

    To develop an easy independent patient-specific quality assurance (QA) method using a benchmark plan for high-dose-rate intracavitary brachytherapy for cervix cancer, we conducted benchmark treatment planning with various sizes and combinations of tandem-ovoid and tandem-cylinder applications with 'ideal' geometry outside the patient. Two-dimensional-based treatment planning was conducted based on the Manchester method. We predicted the total dwell time of individual treatment plans from the air kerma strength, total dwell time and prescription dose of the benchmark plan. In addition, we recorded the height (dh), width (dw) and thickness (dt) covered with 100% isodose line. These parameters were compared with 169 and 29 clinical cases for tandem-ovoid or tandem-cylinder cases, respectively. With regard to tandem-ovoid cases, differences in total dwell time, dh, dt and dw between benchmark and individual plans were on average -0.2% ± 3.8%, -1.0 mm ± 2.6 mm, 0.8 mm ± 1.3 mm and -0.1 mm ± 1.5 mm, respectively. With regard to tandem-cylinder cases, differences in total dwell time, dh(front) (the distance from tandem tip to tandem ring), dt and dw between benchmark and individual plans were on average -1.5% ± 3.1%, -1.5 mm ± 4.9 mm, 0.1 mm ± 1.0 mm and 0.2 mm ± 0.8 mm, respectively. Of two cases, more than 13% differences in total dwell time were observed between benchmark plans and the clinical cases, which turned out to be due to the use of the wrong source position setting. These results suggest that our method is easy and useful for independent verification of patient-specific treatment planning QA.

  19. Identifying the optimal criteria of radiotherapeutic parameters for patients with unresectable locally advanced hepatocellular carcinoma.

    PubMed

    Son, Seok Hyun; Jang, Hong Seok; Sung, Soo Yoon; Kang, Hye Jin; Lee, Sojung; Kay, Chul Seung

    2015-12-01

    The purpose of this study is to identify the optimal criteria of the radiotherapeutic parameters in patients with unresectable locally advanced hepatocellular carcinoma (HCC). 103 patients were enrolled in this study. All patients received RT delivered using the TomoTherapy Hi-Art system between March 2006 and February 2012. We evaluated the planning target volume (PTV), total dose (Gy10), and NTNL-V(BED20) (non-target normal liver volume receiving more than a biologically effective dose of 20 Gy8) as significant radiotherapeutic parameters associated with hepatic function deterioration and local progression-free survival (PFS). A PTV of 279 cm3 or 304 cm3, a total dose of 60 Gy10, and a NTNL-V(BED20) of 40.8% were identified as the optimal cut-off values of radiotherapeutic parameters to prevent hepatic function deterioration and prolong local PFS. Based on these findings, patients were divided in a favorable and an unfavorable prognosis group. The differences in median local PFS, overall survival, and incidence of deteriorated hepatic function between the two groups were 11.2 months, 11.1 months, and 71.7%, respectively (p < 0.001 in each case). In conclusion, we suggest that the optimal criteria of the radiotherapeutic parameters for patients with unresectable locally advanced HCC are: PTV ≤ 279 cm3, total dose > 60 Gy10, and NTNL-V(BED20) ≤ 40.8%. PMID:26510905

  20. Nimotuzumab combined with concurrent chemoradiotherapy in locally advanced nasopharyngeal carcinoma: a retrospective analysis

    PubMed Central

    Zhou, Yu-juan; Yang, Wen-juan; Qiu, Yan-fang; Wang, Hui

    2016-01-01

    Nimotuzumab is a blocking monoclonal antibody against epidermal growth factor receptor (EGFR). However, little is known about the safety and preliminary efficacy of nimotuzumab combined with concurrent chemoradiotherapy in locally advanced NPC patients. A total of 42 patients diagnosed between 2011 and 2013 were enrolled. Our results demonstrated 38 patients had a complete response (90.5%), 4 patients had a partial response (9.5%). And no patients had progressive disease at early treatment response evaluation, giving an ORR of 100%. The 2-year local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS) and overall survival (OS) were 96.4%, 93.1% and 96.6% respectively. The most common adverse events were mucositis (19 patients), hematology toxicity (14 patients) with 6 and 3 cases of grade 3/4 toxicity respectively. Skin rash was not developed in our 43 patients. Thus, nimotuzumab combined with concurrent chemoradiotherapy showed encouraging outcomes in the treatment of locally advanced nasopharyngeal carcinoma, without accumulation of toxicity and well-tolerated. PMID:27016412

  1. Predictive biomarkers of sorafenib efficacy in advanced hepatocellular carcinoma: Are we getting there?

    PubMed Central

    Shao, Yu-Yun; Hsu, Chih-Hung; Cheng, Ann-Lii

    2015-01-01

    Sorafenib is the current standard treatment for advanced hepatocellular carcinoma (HCC), but its efficacy is modest with low response rates and short response duration. Predictive biomarkers for sorafenib efficacy are necessary. However, efforts to determine biomarkers for sorafenib have led only to potential candidates rather than clinically useful predictors. Studies based on patient cohorts identified the potential of blood levels of angiopoietin-2, hepatocyte growth factor, insulin-like growth factor-1, and transforming growth factor-β1 for predicting sorafenib efficacy. Alpha-fetoprotein response, dynamic contrast-enhanced magnetic resonance imaging, and treatment-related side effects may serve as early surrogate markers. Novel approaches based on super-responders or experimental mouse models may provide new directions in biomarker research. These studies identified tumor amplification of FGF3/FGF4 or VEGFA and tumor expression of phospho-Mapk14 and phospho-Atf2 as possible predictive markers that await validation. A group effort that considers various prognostic factors and proper collection of tumor tissues before treatment is imperative for the success of future biomarker research in advanced HCC. PMID:26420960

  2. Safety and efficacy of sorafenib in patients with Child-Pugh B advanced hepatocellular carcinoma

    PubMed Central

    DA FONSECA, LEONARDO GOMES; BARROSO-SOUSA, ROMUALDO; BENTO, AFONSO DA SILVA ALVES; BLANCO, BRUNA PACCOLA; VALENTE, GABRIEL LUIS; PFIFFER, TULIO EDUARDO FLESCH; HOFF, PAULO MARCELO; SABBAGA, JORGE

    2015-01-01

    Sorafenib demonstrated a survival benefit in the treatment of advanced hepatocellular carcinoma (HCC) in phase III trials. However, almost all the patients included in those trials exhibited well-preserved liver function (Child-Pugh A). The aim of this study was to describe our experience with sorafenib in Child-Pugh B HCC patients. A database of patients with advanced HCC treated with sorafenib was retrospectively evaluated. The median overall survival of Child-Pugh B patients (n=20) was 2.53 months [95% confidence interval (CI): 0.33–5.92 months] and of Child-Pugh A patients (n=100) 9.71 months (95% CI: 6.22–13.04). Child-Pugh B patients had a significantly poorer survival compared to Child-Pugh A patients (P=0.002). The toxicities were similar between the two groups. Metastasis, vascular invasion and α-fetoprotein level >1,030 ng/ml were not associated with survival among Child-Pugh B patients (P=0.281, 0.189 and 0.996, respectively). Although the survival outcomes were worse in Child-Pugh B patients treated with sorafenib, the toxicity profile was manageable. Therefore, there remains the question of whether to treat this subgroup of patients and more data are required to define the role of sorafenib in the context of liver dysfunction. PMID:26171182

  3. Predictive biomarkers of sorafenib efficacy in advanced hepatocellular carcinoma: Are we getting there?

    PubMed

    Shao, Yu-Yun; Hsu, Chih-Hung; Cheng, Ann-Lii

    2015-09-28

    Sorafenib is the current standard treatment for advanced hepatocellular carcinoma (HCC), but its efficacy is modest with low response rates and short response duration. Predictive biomarkers for sorafenib efficacy are necessary. However, efforts to determine biomarkers for sorafenib have led only to potential candidates rather than clinically useful predictors. Studies based on patient cohorts identified the potential of blood levels of angiopoietin-2, hepatocyte growth factor, insulin-like growth factor-1, and transforming growth factor-β1 for predicting sorafenib efficacy. Alpha-fetoprotein response, dynamic contrast-enhanced magnetic resonance imaging, and treatment-related side effects may serve as early surrogate markers. Novel approaches based on super-responders or experimental mouse models may provide new directions in biomarker research. These studies identified tumor amplification of FGF3/FGF4 or VEGFA and tumor expression of phospho-Mapk14 and phospho-Atf2 as possible predictive markers that await validation. A group effort that considers various prognostic factors and proper collection of tumor tissues before treatment is imperative for the success of future biomarker research in advanced HCC.

  4. Recent Advances in CT and MR Imaging for Evaluation of Hepatocellular Carcinoma

    PubMed Central

    Lee, Jeong Min; Yoon, Jeong-Hee; Joo, Ijin; Woo, Hyun Sik

    2012-01-01

    Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Accurate diagnosis and assessment of disease extent are crucial for proper management of patients with HCC. Imaging plays a crucial role in early detection, accurate staging, and the planning of management strategies. A variety of imaging modalities are currently used in evaluating patients with suspected HCC; these include ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), nuclear medicine, and angiography. Among these modalities, dynamic MRI and CT are regarded as the best imaging techniques available for the noninvasive diagnosis of HCC. Recent improvements in CT and MRI technology have made noninvasive and reliable diagnostic assessment of hepatocellular nodules possible in the cirrhotic liver, and biopsy is frequently not required prior to treatment. Until now, the major challenge for radiologists in imaging cirrhosis has been the characterization of small cirrhotic nodules smaller than 2 cm in diameter. Further technological advancement will undoubtedly have a major impact on liver tumor imaging. The increased speed of data acquisition in CT and MRI has allowed improvements in both spatial and temporal resolution, which have made possible a more precise evaluation of the hemodynamics of liver nodules. Furthermore, the development of new, tissue-specific contrast agents such as gadoxetic acid has improved HCC detection on MRI. In this review, we discuss the role of CT and MRI in the diagnosis and staging of HCC, recent technological advances, and the strengths and limitations of these imaging modalities. PMID:24159569

  5. Recent advances in renal cell carcinoma from a pathological point of view.

    PubMed

    Mikami, Shuji; Oya, Mototsugu; Mizuno, Ryuichi; Kosaka, Takeo; Ishida, Masaru; Kuroda, Naoto; Nagashima, Yoji; Katsube, Ken-Ichi; Okada, Yasunori

    2016-09-01

    The purpose of this article is to review the recent advances in renal cell carcinoma (RCC) from a pathological point of view. Because the genetic features and morphological characteristics have become major criteria for the classification of RCC, special techniques, such as immunohistochemistry, are essential to the differential diagnosis of renal tumors. Metastasis is frequently observed among the RCC patients with curative nephrectomy, and extracellular matrix-degrading enzymes, such as matrix metalloproteinases (MMP) and heparanase, play a key role in invasion and metastasis of RCC. Snail and Slug, transcription factors of epithelial-mesenchymal transition (EMT), accelerate cancer cell invasion through downregulation of E-cadherin and up-regulation of MMP. Therapies targeted at the vascular endothelial growth factor pathway have become the standard treatment of metastatic RCC. Although they lead to tumor shrinkage mainly by inhibiting angiogenesis, they have typically been associated with drug resistance. The mechanism of the resistance remains largely unknown, but complex events including re-activation of angiogenesis, EMT and cancer stem cells, and immune escape are implicated in the refractory response to the therapy. Recent advances of the research on RCC have caused the changes of classification and therapy, and pathologists should take overall view of these as integrated pathology.

  6. Reconstruction With Modified Face Lift and Orbicularis Oculi V-Y Advancement Flap for Sebaceous Carcinoma on Temple Area.

    PubMed

    Lee, Byeong Ho; Kim, Joo Hyun; Park, Seong Hoon; Ahn, Duk Kyun; Suh, In Suck; Jeong, Hii Sun

    2015-09-01

    Extraocular sebaceous carcinoma that occurs on sebaceous gland is a rare malignant cancer with unknown causes and nonspecific clinical characters, but with distinct pathology and immunohistochemical finding. In Kangnam Sacred Heart Hospital, there was a case that the result of preoperative punch biopsy was squamous cell carcinoma and malignant proliferating trichilemmal tumor, but that of postoperative permanent biopsy was sebaceous carcinoma. The type of tumor, differentiation, location, and aesthetic results are considered to get both recurrence-safe and aesthetically pleasing result. Various flaps were considered, and modified face-lift flap, forehead rotation flap, orbicularis oculi V-Y advancement flap were planned. There were no sign of recurrence of cancer or functional and aesthetical deformities 6 months after the surgery. PMID:26267581

  7. Rapid hyperfractionated radiotherapy. Clinical results in 178 advanced squamous cell carcinomas of the head and neck

    SciTech Connect

    Nguyen, T.D.; Demange, L.; Froissart, D.; Panis, X.; Loirette, M.

    1985-07-01

    The authors present a series of 178 patients with Stage III or IV squamous cell carcinoma of the head and neck treated by rapid irradiation using multiple and small fractions per day. An initial group of 91 patients (G1) received a total dose of 72 Gy in 80 sessions and 10 days, according to the following split course schedule: J1 to J5, 36 Gy in 40 sessions, eight daily fractions of .9 Gy separated by 2 hours; J6 to J20, rest period; J21 to J25, same as in J1 except that the spinal cord was shielded. This protocol was altered for the following 87 patients (G2) by lessening the total dose to 60 to 66 Gy and the number of fractions to 60. The rest period was lengthened to 4 weeks. All patients but five completed the whole program and the minimal follow-up period was 24 months. At the end of irradiation, 121 patients achieved a total remission, but local recurrences occurred in 56%. Moreover, acute intolerance was considered as severe in 34% of G1 patients, and included extensive mucosal necrosis and bleeding. Although this rate was significantly reduced in G2 patients, late complications were observed in 20 of the 25 survivors, and included trismus, cervical sclerosis, and recurrent laryngeal edema. The crude survival rate is 13% at 2 years. Although this study was not randomized, this particular type of accelerated and hyperfractionated combination of irradiation did not really improve the clinical results in advanced carcinoma of the head and neck. Other schedules and probably other tumors, less extended, should be tested.

  8. A Systematic Evaluation of Collagen Crosslinks in the Human Cervix

    PubMed Central

    Zork, Noelia M; Myers, Kristin Marie; Yoshida, Ms. Kyoko; Cremers, Serge; Jiang, Hongfeng; Ananth, Cande V; Wapner, Ronald; Kitajewski, Jan; Vink, Joy

    2014-01-01

    Objective The mechanical strength of the cervix relies on crosslinking of the tissue’s collagen network. Clinically, the internal os is functionally distinct from the external os. We sought to detect specific collagen crosslinks in human cervical tissue and determine if crosslink profiles were similar at the internal and external os. Study Design Transverse slices of cervical tissue were obtained at the internal and external os from 13 non-pregnant, premenopausal women undergoing a benign hysterectomy. To understand how crosslinks were distributed throughout the entire cervix and at the internal and external os, biopsies were obtained from three circumferential zones in four quadrants from each slice. Biopsies were pulverized, lyophilized, reduced with sodium borohydride, hydrolyzed with hydrochloric acid and reconstituted in heptafluorobutyric acid buffer. Hydroxyproline was measured by ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS), converted to total collagen, and normalized by dry weight. Collagen crosslinks pyridinoline (PYD), deoxypyridinoline (DPD), dihydroxylysinonorleucine (DHLNL), and the nonenzymatic advanced glycation end product pentosidine [PEN] were measured by UPLC-ESI-MS/MS and reported as crosslink density ratio (crosslink:total collagen). Generalized estimated equation analysis was used to compare results between the internal and external os and to compare quadrants and zones within slices from the internal and external os to determine if crosslink profiles were similar. Results 592 samples from 13 patients were analyzed. Collagen crosslinks are detectable in the human cervix by UPLC-ESI-MS/MS. When comparing all samples from the internal and external os, similar levels of collagen content, PYD, DHLNL and DPD were found but PEN density was higher at the external os (0.005 vs 0.004, P=0.001). When comparing all internal os samples, significant heterogeneity was found in collagen content

  9. Transcatheter Arterial Chemoembolization for Advanced Hepatocellular Carcinoma with Inferior Vena Cava and Right Atrial Tumors

    SciTech Connect

    Chern, M. C. Chuang, V. P. Cheng, T. Lin, Z. H. Lin, Y. M.

    2008-07-15

    Advanced hepatocelluar carcinoma (HCC) with invasion of venous systems usually indicates not only a poor prognosis but also a contraindication for transcatheter arterial chemoembolization (TACE). This study evaluated the feasibility of TACE for advanced HCC with inferior vena cava (IVC) and right atrium (RA) tumors and, also, to search for the ideal embolization particle size. Twenty-six patients who had HCC invasion into the IVC included five patients with coexistent RA tumors that were treated with TACE. The chemoembolization method was cisplatin, doxorubicin, and mitomycin C mixed with Lipiodol and Ivalon. The selection of Ivalon particles was divided into two groups based on their size: (A) >180 {mu}m, N = 9; and (B) 47-180 {mu}m, N = 17. The overall response rate was 53.8% (14/26). Based on the response to TACE, the median survival period of the entire group was 4.2 months (range, 1.5 to 76.7 months). The median survival period of the 14 responders was 13.5 months (1.5-76.7 months), and that of the 12 nonresponders, 3.3 months (2.1 to 24.3 months) (p < 0.002). Comparing the two Ivalon particle sizes, the response rate was 12.5% (1/9 patients) for group A and 76.5% for group B (13/17 patients) (p < 0.02). No serious complication was observed post-chemoembolization. In conclusion, TACE is a safe and effective treatment for advanced HCC with IVC and RA tumors, and small Ivalon particles (47-180 {mu}m) are superior to large ones (>180 {mu}m).

  10. Case Report of Diffuse Large B Cell Lymphoma of Uterine Cervix Treated at a Semiurban Cancer Centre in North India.

    PubMed

    Sharma, Vibhor; Dora, Tapas; Patel, Mehul; Sancheti, Sankalp; Sridhar, Epari

    2016-01-01

    Lymphoma of the uterine cervix is very rare. We report a case of diffuse large B cell lymphoma (DLBCL) involving the uterine cervix treated at a newly commissioned semiurban cancer centre in north India in 2015. Data for this study was obtained from the hospital electronic medical records and the patient's case file. We also reviewed published case reports of uterine and cervical lymphoma involving forty-one patients. We treated a case of stage IV DLBCL cervix with six cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) and intrathecal methotrexate followed by consolidation with radiotherapy. The patient showed complete response to chemotherapy. We conclude that, in advanced stage lymphoma involving uterus and cervix, combination of chemotherapy and radiotherapy is effective in short term. PMID:27597906

  11. Case Report of Diffuse Large B Cell Lymphoma of Uterine Cervix Treated at a Semiurban Cancer Centre in North India

    PubMed Central

    Sridhar, Epari

    2016-01-01

    Lymphoma of the uterine cervix is very rare. We report a case of diffuse large B cell lymphoma (DLBCL) involving the uterine cervix treated at a newly commissioned semiurban cancer centre in north India in 2015. Data for this study was obtained from the hospital electronic medical records and the patient's case file. We also reviewed published case reports of uterine and cervical lymphoma involving forty-one patients. We treated a case of stage IV DLBCL cervix with six cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) and intrathecal methotrexate followed by consolidation with radiotherapy. The patient showed complete response to chemotherapy. We conclude that, in advanced stage lymphoma involving uterus and cervix, combination of chemotherapy and radiotherapy is effective in short term. PMID:27597906

  12. [Radical hysterectomy for cervix uteri cancer. Experience with 217 patients].

    PubMed

    Torres Lobatón, A; Matías Salvador, M; Hernández Aten, D; Román Bassaure, E

    1991-01-01

    This paper reports an analysis of 217 patients with invasive carcinoma of the cervix, treated with radical histerectomy at The Oncology Service, General Hospital of Mexico. The commonest complications of surgical procedure, were related with the urinary tract: atony bladder observed in 27.6% of patients, vesico-vaginal fistulas in 7.8% and uretero-vaginal fistulas, in 5.5%. Lymph node metastases were present in 20/143, (13.9%) patients classified as belonging to stage Ib and 10/51, (19.6%) of stage IIa, p less than 0.05. After a follow-up period of two years, 92/101, (91%) of patients in stage Ib, 24/32, (75%) in stage IIa, p less than 0.05, 69/73 with tumor less than 2 cm and 111/125, (88.8%) without lymph node metastases, were free of disease. A poor prognosis was related with tumor size of 4 cm or more, 12/18, 66%); adenosquamous carcinomas, (7/11, 63.6%); poorly differentrated carcinomas, (13/20, 65.8%) and lymph node metastases, (8/15, 53.3%).

  13. Prevalence, distribution, and viral burden of all 15 high-risk human papillomavirus types in adenosquamous carcinoma of the uterine cervix: a multiplex real-time polymerase chain reaction-based study.

    PubMed

    Quddus, M Ruhul; Manna, Pradip; Sung, C James; Kerley, Spencer; Steinhoff, Margaret M; Lawrence, W Dwayne

    2014-02-01

    Human papillomavirus (HPV) 16 and 18 are the types most commonly found in cervical adenosquamous carcinoma. Multiple HPV types have been found in cervical adenocarcinoma but not in the adenosquamous variant. Type-specific detection of high-risk (HR) HPV allows the detection of co-infection by multiple HPV types and assessment of viral load per cell. Our aim was to identify and quantify all HR HPV types in cervical adenosquamous carcinoma and to correlate viral loads with prognosis-related histologic features. All 15 HR HPV types were tested for by multiplex real-time polymerase chain reaction, and standard curves were created for each type. Viral loads were determined retrospectively. Prognosis-related histologic features were correlated with specific HPV types and the viral loads. A total of 80% of the tumors examined expressed HPV. Types 16/18 were detected in 86% of these cases, whereas the remaining 14% of the positive cases were infected by other types. A single type of virus was detected in 67% of cases, 2 in 29%, and 3 in 4%. Poor prognostic features were seen in 84.6% of the tumors infected with HPV 16, 46% of those infected with HPV 18, and 100% of those infected with other types. As expected, HPV 16, HPV 18, or both were the most frequent viral types; HPV 73 was the next most frequent type. Multiple HPV types were detected in 33% of the tumors. Non-HPV 16/18 cases had low viral loads, but all of these had poor prognosis-related histologic features. Two of the three recurrent cases had multiple viral types.

  14. Para-aortic lymph node radiation in advanced cervical cancer

    SciTech Connect

    Emami, B.; Watring, W.G.; Tak, W.; Anderson, B.; Piro, A.J.

    1980-09-01

    Thirty-six patients with advanced carcinoma of the uterine cervix and with iliac or para-aortic nodes interpreted as un-equivocally positive on lymphangiography have received radiation therapy to the para-aortic area at the Department of Therapeutic Radiology at Tufts-New England Medical Center Hospital. Of 29 patients who received para-aortic area irradiation as part of their initial treatment, local control was achieved in 18 patients (62%). Overall, four patients developed major complications requiring surgical intervention. Detailed results and our current pre-treatment evaluation policy including lymphangiography, percutaneous needle biopsy and selective extra-peritoneal lymph node biopsy will be discussed.

  15. TERT promoter hot spot mutations are frequent in Indian cervical and oral squamous cell carcinomas.

    PubMed

    Vinothkumar, Vilvanathan; Arunkumar, Ganesan; Revathidevi, Sundaramoorthy; Arun, Kanagaraj; Manikandan, Mayakannan; Rao, Arunagiri Kuha Deva Magendhra; Rajkumar, Kottayasamy Seenivasagam; Ajay, Chandrasekar; Rajaraman, Ramamurthy; Ramani, Rajendren; Murugan, Avaniyapuram Kannan; Munirajan, Arasambattu Kannan

    2016-06-01

    Squamous cell carcinoma (SCC) of the uterine cervix and oral cavity are most common cancers in India. Telomerase reverse transcriptase (TERT) overexpression is one of the hallmarks for cancer, and activation through promoter mutation C228T and C250T has been reported in variety of tumors and often shown to be associated with aggressive tumors. In the present study, we analyzed these two hot spot mutations in 181 primary tumors of the uterine cervix and oral cavity by direct DNA sequencing and correlated with patient's clinicopathological characteristics. We found relatively high frequency of TERT hot spot mutations in both cervical [21.4 % (30/140)] and oral [31.7 % (13/41)] squamous cell carcinomas. In cervical cancer, TERT promoter mutations were more prevalent (25 %) in human papilloma virus (HPV)-negative cases compared to HPV-positive cases (20.6 %), and both TERT promoter mutation and HPV infection were more commonly observed in advanced stage tumors (77 %). Similarly, the poor and moderately differentiated tumors of the uterine cervix had both the TERT hot spot mutations and HPV (16 and 18) at higher frequency (95.7 %). Interestingly, we observed eight homozygous mutations (six 228TT and two 250TT) only in cervical tumors, and all of them were found to be positive for high-risk HPV. To the best of our knowledge, this is the first study from India reporting high prevalence of TERT promoter mutations in primary tumors of the uterine cervix and oral cavity. Our results suggest that TERT reactivation through promoter mutation either alone or in association with the HPV oncogenes (E6 and E7) could play an important role in the carcinogenesis of cervical and oral cancers. PMID:26700669

  16. Long-Term Results of Concurrent Chemoradiotherapy for Advanced N2-3 Stage Nasopharyngeal Carcinoma

    PubMed Central

    Wang, Xue; Chen, Meng; Wu, Jing; Xu, Jian-Hua; Qian, Pu-Dong; Guo, Wen-Jie; Jiang, Xue-Song; Zhu, Huan-Feng; Gu, Jia-Jia; Wu, Jian-Feng; Zhang, Ye-wei; He, Xia

    2015-01-01

    Background N-stage is related to distant metastasis in nasopharyngeal carcinoma (NPC) patients. The purpose of this study was to evaluate the efficacy and toxicity of different nedaplatin-based chemotherapy regimens in advanced N2-3 stage NPC patients treated with intensity modulated radiation therapy (IMRT). Patients and Methods Between April 2005 and December 2009, a total of 128 patients with N2-3 advanced NPC were retrospectively analyzed. Patients were treated with IMRT concurrent with 2 cycles of chemotherapy consisting of either nedaplatin plus paclitaxel (NP group, n = 67) or nedaplatin plus fluorouracil and paclitaxel (NFP group, n = 61). Two to four cycles of adjuvant chemotherapy were then administered every 21 days following concurrent chemoradiotherapy. Results With a median follow-up of 60 months, the 5-year overall survival (OS), progression-free survival (PFS), local-regional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) for all patients were 81.4%, 71.5%, 87.8% and 82.0%, respectively. No significant difference in PFS (66.6% vs. 76.7%, P = 0.212) and LRRFS rates (89.0% vs. 86.3%, P = 0.664) was observed between the NP and NFP groups. The 5-year OS (75.4% vs. 88.5%, P = 0.046) and DMFS (75.1% vs. 89.0%, P = 0.042) rate were superior in the NFP group compared with the NP group. The NFP group had a higher incidence of grade 3–4 acute toxicities including bone marrow suppression (leukopenia: χ2 = 3.935, P = 0.047; anemia: χ2 = 9.760, P = 0.002; thrombocytopenia: χ2 = 8.821, P = 0.003), and both liver and renal dysfunction (χ2 = 5.206, P = 0.023) compared with the NP group. Late toxicities were moderate and no difference was observed between the two groups. Conclusion IMRT concurrent with nedaplatin-based chemotherapy is an advocated regimen for patients with advanced N2-3 stage NPC. Patients with advanced N2-3 stage may be better candidates for the NFP regimen although this regimen was associated with a high acute

  17. Recent Advances in the Imaging Diagnosis of Hepatocellular Carcinoma: Value of Gadoxetic Acid-Enhanced MRI

    PubMed Central

    Joo, Ijin; Lee, Jeong Min

    2016-01-01

    Magnetic resonance imaging (MRI) using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DPTA), or gadoxetic acid for short, is a hepatocyte-specific contrast agent which is now increasingly used for the detection and characterization of focal hepatic lesions, particularly in patients at high-risk of developing hepatocellular carcinomas (HCC). In fact, several recent guidelines now recognize gadoxetic acid-enhanced MRI (Gd-EOB-MRI) as the primary diagnostic imaging modality for the noninvasive diagnosis of HCC, although it must be noted that several major guidelines still include only extracellular contrast media-enhanced computed tomography and MRI. The primary merits of Gd-EOB-MRI lie in the fact that it can provide not only dynamic imaging, but also hepatobiliary phase (HBP) imaging which can lead to high lesion-to-liver contrast and give additional information regarding hepatocyte uptake via organic anion transporting polypeptides. This, in turn, allows higher sensitivity in detecting small HCCs and helps provide additional information regarding the multistep process of hepatocarcinogenesis. Indeed, many recent studies have investigated the diagnostic value of Gd-EOB-MRI for early HCCs as well as its role as a potential imaging biomarker in predicting outcome. We herein review the recent advances in the imaging diagnosis of HCCs focusing on the applications of Gd-EOB-MRI and the challenging issues that remain. PMID:26989660

  18. Neurological Adverse Effects in Patients of Advanced Colorectal Carcinoma Treated with Different Schedules of FOLFOX

    PubMed Central

    Najam, Rahila; Mateen, Ahmed

    2013-01-01

    The study is designed to assess the frequency and severity of few dose limiting neurological adverse effects of four different schedules of FOLFOX. Patients with histologically confirmed advanced colorectal carcinoma (CRC) were included in the study. Toxicity was graded according to CTC v 2.0. The frequency of grade 3 and 4 adverse effects was comparatively assessed in each treatment arm. The difference in the pattern of toxicity between the treatment schedule was evaluated. The most frequent adverse symptom of neurological adverse effect was grade 1 paresthesia in the patients treated with FOLFOX4 schedule. Grade 4 peripheral neuropathy was reported in few patients of FOLFOX7 treatment arm. Frequency and onset of neurological adverse effects like paresthesia, dizziness, and hypoesthesia were significantly different (P < 0.05), whereas frequency and onset of peripheral neuropathy were highly significant (P < 0.01) in each treatment arm of FOLFOX. Peripheral neuropathy was associated with electrolyte imbalance and diabetes in few patients. Frequency of symptoms, for example, paresthesia, is associated with increased number of recurrent exposure to oxaliplatin (increased number of cycles) even at low doses (85 mg/m2), whereas severity of symptoms, for example, peripheral neuropathy, is associated with higher dose (130 mg/m2) after few treatment cycles. PMID:24187619

  19. Neurological Adverse Effects in Patients of Advanced Colorectal Carcinoma Treated with Different Schedules of FOLFOX.

    PubMed

    Bano, Nusrat; Najam, Rahila; Mateen, Ahmed

    2013-01-01

    The study is designed to assess the frequency and severity of few dose limiting neurological adverse effects of four different schedules of FOLFOX. Patients with histologically confirmed advanced colorectal carcinoma (CRC) were included in the study. Toxicity was graded according to CTC v 2.0. The frequency of grade 3 and 4 adverse effects was comparatively assessed in each treatment arm. The difference in the pattern of toxicity between the treatment schedule was evaluated. The most frequent adverse symptom of neurological adverse effect was grade 1 paresthesia in the patients treated with FOLFOX4 schedule. Grade 4 peripheral neuropathy was reported in few patients of FOLFOX7 treatment arm. Frequency and onset of neurological adverse effects like paresthesia, dizziness, and hypoesthesia were significantly different (P < 0.05), whereas frequency and onset of peripheral neuropathy were highly significant (P < 0.01) in each treatment arm of FOLFOX. Peripheral neuropathy was associated with electrolyte imbalance and diabetes in few patients. Frequency of symptoms, for example, paresthesia, is associated with increased number of recurrent exposure to oxaliplatin (increased number of cycles) even at low doses (85 mg/m(2)), whereas severity of symptoms, for example, peripheral neuropathy, is associated with higher dose (130 mg/m(2)) after few treatment cycles.

  20. [Plasma Biomarkers as Predictive Factors for Advanced Hepatocellular Carcinoma with Sorafenib].

    PubMed

    Shiozawa, Kazue; Watanabe, Manabu; Ikehara, Takashi; Matsukiyo, Yasushi; Kogame, Michio; Shinohara, Mie; Kikuchi, Yoshinori; Igarashi, Yoshinori; Sumino, Yasukiyo

    2016-07-01

    We examined plasma biomarkers as predictive factors for advanced hepatocellular carcinoma(ad-HCC)patients treated with sorafenib. We analyzed a-fetoprotein(AFP), AFP-L3, des-g-carboxy prothrombin(DCP), neutrophil-to-lymphocyte ratio(NLR), platelet-to-lymphocyte ratio(PLR), and vascular endothelial growth factor(VEGF)before sorafenib therapy, and changes in AFP-L3, NLR, PLR, and VEGF 1 month after sorafenib therapy in 16 patients. High AFP-L3(hazard ratio: 1.058, 95%CI: 1.019-1.098, p=0.003)and high NLR(hazard ratio: 1.475, 95%CI: 1.045-2.082, p=0.027)were significantly associated with poor prognosis in ad-HCC patients treated with sorafenib. There were no significant differences in changes in AFP-L3, NLR, PLR, and VEGF 1 month after sorafenib therapy. We suggest that AFP-L3 and NLR levels before sorafenib therapy in patients with ad-HCC are an important predictive factor for the therapeutic effect of sorafenib and patient survival. PMID:27431630

  1. Non-coding RNAs deregulation in oral squamous cell carcinoma: advances and challenges.

    PubMed

    Yu, T; Li, C; Wang, Z; Liu, K; Xu, C; Yang, Q; Tang, Y; Wu, Y

    2016-05-01

    Oral squamous cell carcinoma (OSCC) is a common cause of cancer death. Despite decades of improvements in exploring new treatments and considerable advance in multimodality treatment, satisfactory curative rates have not yet been reached. The difficulty of early diagnosis and the high prevalence of metastasis associated with OSCC contribute to its dismal prognosis. In the last few decades the emerging data from both tumor biology and clinical trials led to growing interest in the research for predictive biomarkers. Non-coding RNAs (ncRNAs) are promising biomarkers. Among numerous kinds of ncRNAs, short ncRNAs, such as microRNAs (miRNAs), have been extensively investigated with regard to their biogenesis, function, and importance in carcinogenesis. In contrast to miRNAs, long non-coding RNAs (lncRNAs) are much less known concerning their functions in human cancers especially in OSCC. The present review highlighted the roles of miRNAs and newly discovered lncRNAs in oral tumorigenesis, metastasis, and their clinical implication.

  2. Pazopanib: a multikinase inhibitor with activity in advanced renal cell carcinoma.

    PubMed

    Bukowski, Ronald M

    2010-05-01

    Treatment options for patients with metastatic renal cell carcinoma (RCC) have changed dramatically, and a new paradigm has evolved. IFN-alpha and IL-2 were previously mainstays of therapy, but since December 2005, six new agents have been approved in the USA for the treatment of advanced RCC. Three of these new agents are multitargeted kinase inhibitors, including sunitinib, sorafenib, and recently pazopanib, two target the mTOR (temsirolimus and everolimus), and one is a humanized monoclonal antibody (bevacizumab in combination with IFN-alpha) that targets VEGF. Sunitinib has emerged as the standard of care for treatment-naive RCC patients, with the recently approved bevacizumab and IFN-alpha combination providing an additional option for this population. The recent approval of pazopanib, based on the results from sequential Phase II and III clinical trials demonstrating improved overall response rates and progression-free survival, provides yet another option for front-line therapy. The current article examines the pazopanib preclinical and clinical data, provides an overview of the development of this tyrosine kinase inhibitor, and provides some speculation concerning its role in RCC therapy.

  3. Advanced imaging techniques in the therapeutic response of transarterial chemoembolization for hepatocellular carcinoma

    PubMed Central

    Yang, Ke; Zhang, Xiao-Ming; Yang, Lin; Xu, Hao; Peng, Juan

    2016-01-01

    Hepatocellular carcinoma (HCC) is one of the major causes of morbidity and mortality in patients with chronic liver disease. Transarterial chemoembolization (TACE) can significantly improve the survival rate of patients with HCC and is the first treatment choice for patients who are not suitable for surgical resections. The evaluation of the response to TACE treatment affects not only the assessment of the therapy efficacy but also the development of the next step in the treatment plan. The use of imaging to examine changes in tumor volume to assess the response of solid tumors to treatment has been controversial. In recent years, the emergence of new imaging technology has made it possible to observe the response of tumors to treatment prior to any morphological changes. In this article, the advances in studies reporting the use of computed tomography perfusion imaging, diffusion-weighted magnetic resonance imaging (MRI), intravoxel incoherent motion, diffusion kurtosis imaging, magnetic resonance spectroscopy, magnetic resonance perfusion-weighted imaging, blood oxygen level-dependent MRI, positron emission tomography (PET)/computed tomography and PET/MRI to assess the TACE treatment response are reviewed. PMID:27239110

  4. A phase I clinical trial of thymidine kinase-based gene therapy in advanced hepatocellular carcinoma.

    PubMed

    Sangro, B; Mazzolini, G; Ruiz, M; Ruiz, J; Quiroga, J; Herrero, I; Qian, C; Benito, A; Larrache, J; Olagüe, C; Boan, J; Peñuelas, I; Sádaba, B; Prieto, J

    2010-12-01

    The aim of this phase I clinical trial was to assess the feasibility and safety of intratumoral administration of a first-generation adenoviral vector encoding herpes simplex virus thymidine kinase (HSV-TK) gene (Ad.TK) followed by systemic ganciclovir to patients with advanced hepatocellular carcinoma (HCC). Secondarily, we have analyzed its antitumor effect. Ten patients were enrolled in five dose-level cohorts that received from 10¹⁰ to 2 × 10¹² viral particles (vp). Ad.TK was injected intratumorally and patients received up to three doses at 30-day intervals. Positron emission tomography was used to monitor TK gene expression. Ad.TK injection was feasible in 100% of cases. Treatment was well tolerated and dose-limiting toxicity was not achieved. Cumulative toxicity was not observed. Hepatic toxicity was absent even in cirrhotic patients. Fever, flu-like syndrome, pain at the injection site and pancytopenia were the most common side effects. No partial responses were observed and 60% of patients showed tumor stabilization of the injected lesion. Importantly, two patients who received the highest dose showed signs of intratumoral necrosis by imaging procedures. One of them achieved a sustained stabilization and survived for 26 months. In conclusion, Ad.TK can be safely administered by intratumoral injection to patients with HCC up to 2 × 10¹² vp per patient. PMID:20689572

  5. Recent Advances in the Imaging Diagnosis of Hepatocellular Carcinoma: Value of Gadoxetic Acid-Enhanced MRI.

    PubMed

    Joo, Ijin; Lee, Jeong Min

    2016-02-01

    Magnetic resonance imaging (MRI) using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DPTA), or gadoxetic acid for short, is a hepatocyte-specific contrast agent which is now increasingly used for the detection and characterization of focal hepatic lesions, particularly in patients at high-risk of developing hepatocellular carcinomas (HCC). In fact, several recent guidelines now recognize gadoxetic acid-enhanced MRI (Gd-EOB-MRI) as the primary diagnostic imaging modality for the noninvasive diagnosis of HCC, although it must be noted that several major guidelines still include only extracellular contrast media-enhanced computed tomography and MRI. The primary merits of Gd-EOB-MRI lie in the fact that it can provide not only dynamic imaging, but also hepatobiliary phase (HBP) imaging which can lead to high lesion-to-liver contrast and give additional information regarding hepatocyte uptake via organic anion transporting polypeptides. This, in turn, allows higher sensitivity in detecting small HCCs and helps provide additional information regarding the multistep process of hepatocarcinogenesis. Indeed, many recent studies have investigated the diagnostic value of Gd-EOB-MRI for early HCCs as well as its role as a potential imaging biomarker in predicting outcome. We herein review the recent advances in the imaging diagnosis of HCCs focusing on the applications of Gd-EOB-MRI and the challenging issues that remain. PMID:26989660

  6. Combined-modality treatment for advanced oral tongue squamous cell carcinoma

    SciTech Connect

    Fan, K.-H.; Lin, C.-Y. |; Kang, C.-J.; Huang, S.-F.; Chen, I.-H.; Liao, C.-T. |; Wang, H.-M. |; Cheng, A.-J. |; Chang, J.T.-C. ||. E-mail: jtchang@adm.cgmh.org.tw

    2007-02-01

    Purpose: The aim of this study was to investigate prognostic factors in advanced-stage oral tongue cancer treated with postoperative adjuvant therapy and to identify indications for adjuvant concomitant chemoradiotherapy (CCRT). Methods and Materials: We retrospectively reviewed the records of 201 patients with advanced squamous cell carcinoma of the oral tongue managed between January 1995 and November 2002. All had undergone wide excision and neck dissection plus adjuvant radiotherapy or CCRT. Based on postoperative staging, 123 (61.2%) patients had Stage IV and 78 (38.8%) had Stage III disease. All patients were followed for at least 18 months after completion of radiotherapy or until death. The median follow-up was 40.4 months for surviving patients. The median dose of radiotherapy was 64.8 Gy (range, 58.8-72.8 Gy). Cisplatin-based regimens were used for chemotherapy. Results: The 3-year overall survival (OS) and recurrence-free survival (RFS) rates were 48% and 50.8%, respectively. Stage, multiple nodal metastases, differentiation, and extracapsular spread (ECS) significantly affected disease-specific survival on univariate analysis. On multivariate analysis, multiple nodal metastases, differentiation, ECS, and CCRT were independent prognostic factors. If ECS was present, only CCRT significantly improved survival (3-year RFS with ECS and with CCRT = 48.2% vs. without CCRT = 15%, p = 0.038). In the presence of other poor prognostic factors, results of the two treatment strategies did not significantly differ. Conclusions: Based on this study, ECS appears to be an absolute indication for adjuvant CCRT. CCRT can not be shown to be statistically better than radiotherapy alone in this retrospective series when ECS is not present.

  7. Efficacy, Safety, and Biomarkers of Single-Agent Bevacizumab Therapy in Patients with Advanced Hepatocellular Carcinoma

    PubMed Central

    Malka, David; Bourredjem, Abderrahmane; Dromain, Clarisse; Baey, Charlotte; Jacques, Nathalie; Pignon, Jean-Pierre; Vimond, Nadege; Bouvet-Forteau, Nathalie; De Baere, Thierry; Ducreux, Michel; Farace, Françoise

    2012-01-01

    Objective. Hepatocellular carcinoma (HCC) is a highly vascularized tumor in which neoangiogenesis contributes to growth and metastasis. We assessed the safety, efficacy, and potential biomarkers of activity of bevacizumab in patients with advanced HCC. Methods. In this phase II trial, eligible patients received bevacizumab, 5 mg/kg or 10 mg/kg every 2 weeks. The disease-control rate at 16 weeks (16W-DCR) was the primary endpoint. Circulating endothelial cells (CECs) and plasma cytokines and angiogenic factors (CAFs) were measured at baseline and throughout treatment. Results. The 16W-DCR was 42% (95% confidence interval, 27%–57%). Six of the 43 patients who received bevacizumab achieved a partial response (objective response rate [ORR], 14%). Grade 3–4 asthenia, hemorrhage, and aminotransferase elevation occurred in five (12%), three (7%), and three (7%) patients, respectively. During treatment, placental growth factor markedly increased, whereas vascular endothelial growth factor (VEGF)-A dramatically decreased (p < .0001); soluble VEGF receptor-2 (p < .0001) and CECs (p = .03) transiently increased on day 3. High and increased CEC counts at day 15 were associated with the ORR (p = .04) and the 16W-DCR (p = .02), respectively. Lower interleukin (IL)-8 levels at baseline (p = .01) and throughout treatment (p ≤ .04) were associated with the 16W-DCR. High baseline IL-8 and IL-6 levels predicted shorter progression-free and overall survival times (p ≤ .04). Conclusion. Bevacizumab is active and well tolerated in patients with advanced HCC. The clinical value of CECs, IL-6, and IL-8 warrants further investigation. PMID:22707516

  8. Advanced hepatocellular carcinoma and sorafenib: Diagnosis, indications, clinical and radiological follow-up.

    PubMed

    Colagrande, Stefano; Regini, Francesco; Taliani, Gian Giacomo; Nardi, Cosimo; Inghilesi, Andrea Lorenzo

    2015-05-18

    Advanced stage hepatocellular carcinoma (HCC) is a category of disease defined by radiological, clinical and hepatic function parameters, comprehending a wide range of patients with different general conditions. The main therapeutic option is represented by sorafenib treatment, a multi-kinase inhibitor with anti-proliferative and anti-angiogenic effect. Trans-arterial Radio Embolization also represents a promising new approach to intermediate/advanced HCC. Post-marketing clinical studies showed that only a portion of patients actually benefits from sorafenib treatment, and an even smaller percentage of patients treated shows partial/complete response on follow-up examinations, up against relevant costs and an incidence of drug related adverse effects. Although the treatment with sorafenib has shown a significant increase in mean overall survival in different studies, only a part of patients actually shows real benefits, while the incidence of drug related significant adverse effects and the economic costs are relatively high. Moreover, only a small percentage of patients also shows a response in terms of lesion dimensions reduction. Being able to properly differentiate patients who are responding to the therapy from non-responders as early as possible is then still difficult and could be a pivotal challenge for the future; in fact it could spare several patients a therapy often difficult to bear, directing them to other second line treatments (many of which are at the moment still under investigation). For this reason, some supplemental criteria to be added to the standard modified Response Evaluation Criteria in Solid Tumors evaluation are being searched for. In particular, finding some parameters (cellular density, perfusion grade and enhancement rate) able to predict the sensitivity of the lesions to anti-angiogenic agents could help in stratifying patients in terms of treatment responsiveness before the beginning of the therapy itself, or in the first weeks of

  9. Lack of prognostic relevance of Her-2/neu, topoisomerase IIα and EGFR in advanced ovarian carcinoma

    PubMed Central

    ENGELSTAEDTER, VERENA; BODA, JUDITH; VÖLKLEIN, CHRISTINE; ENGEL, JUTTA; JESCHKE, UDO; KIRCHNER, THOMAS; MAYR, DORIS

    2012-01-01

    Patients with advanced ovarian cancer (FIGO stage III) have a poor clinical prognosis. However, these patients show distinct differences in their survival time, possibly due to differing responses to chemotherapy and differing tumor biology. In contrast to histological subtype, grading and staging, which are known to affect a patient’s prognosis, the impact of the human epidermal growth factor receptor 2 (Her-2/neu), topoisomerase IIα and epidermal growth factor receptor (EGFR) on survival remain inconclusive. Therefore, the aim of this study was to assess their impact on survival in a group of advanced ovarian cancer patients. Tissue microarrays were constructed from specimens of 243 patients. Gene copy and chromosome numbers were evaluated by fluorescence in situ hybridization (FISH) and protein expression by immunohistochemistry (IHC). Scoring for the latter was calculated by considering the percentage of positive tumor cells and the relative staining intensity. FISH results were evaluated by previously published recommendations and correlated with overall survival. Using IHC, 1.6% of the cases that were tested for Her-2/neu and topoisomerase IIα were strongly positive, and 12.3% were positive for EGFR. Using FISH, 4.4% amplifications and 2.1% polysomies for Her-2/neu were identified; topoisomerase IIα showed 2.2% amplifications, 0.4% deletions and 3.5% polysomies. We observed 10.8% high polysomies, but no amplification for EGFR. None of the results obtained by IHC or FISH correlated with overall survival. In general, Her-2/neu, topoisomerase IIα and EGFR may be prognostic factors in ovarian carcinomas. However, within this group of FIGO stage III patients, differences in gene aberration or protein expression were not able to predict differences in survival. PMID:22969977

  10. Helical Tomotherapy and Larynx Sparing in Advanced Oropharyngeal Carcinoma: A Dosimetric Study

    SciTech Connect

    Gielda, Benjamin T.; Millunchick, Cheryl H.; Smart, Joseph P.; Marsh, James C.; Turian, Julius V.; Coleman, Joy L.

    2010-10-01

    Intensity-modulated radiation therapy (IMRT) is gaining acceptance as a standard treatment technique for advanced squamous cell carcinoma (SCC) of the oropharynx. Dose to the uninvolved larynx and surrounding structures can pose a problem in patients with significant neck disease, potentially compromising laryngeal function and quality of life. Tomotherapy may allow greater laryngeal sparing. Seven patients with stage IV SCC of the oropharynx were replanned using Tomotherapy version 3.1. All contours/planning target volumes (PTVs) from the original plans were preserved, with the exception of the larynx, which was drawn to include all soft tissue encompassed by the thyroid/cricoid cartilage. A simultaneous integrated boost technique was used with PTV 1, 2, and 3 receiving 69.96, 59.40, and 54.00 Gy, respectively in 33 fractions. Dosimetry was evaluated via the Pinnacle treatment planning system (TPS). Equivalent uniform dose (EUD) was calculated from the dose volume histogram (DVH) using the general method with 'a' = 5.0. Mean larynx dose for all patients was 24.4 Gy. Mean EUD to the larynx was 34.2 Gy. Homogeneity was adequate; average maximum dose was 109.7% of the highest prescription. All other organs at risk (OAR) were adequately spared. Tomotherapy can spare the uninvolved larynx in the setting of advanced SCC of the oropharynx to levels that are similar to or better than those reported with other techniques. Sparing is achieved without compromising target coverage or other OAR sparing. The clinical benefit of this sparing remains to be determined in a prospective study.

  11. Comprehensive Genomic Profiling of Advanced Esophageal Squamous Cell Carcinomas and Esophageal Adenocarcinomas Reveals Similarities and Differences

    PubMed Central

    Johnson, Adrienne; Ali, Siraj M.; Klempner, Samuel J.; Bekaii-Saab, Tanios; Vacirca, Jeffrey L.; Khaira, Depinder; Yelensky, Roman; Chmielecki, Juliann; Elvin, Julia A.; Lipson, Doron; Miller, Vincent A.; Stephens, Philip J.; Ross, Jeffrey S.

    2015-01-01

    Background. Esophageal squamous cell carcinomas (ESCCs) and esophageal adenocarcinomas (EACs) account for >95% of esophageal malignancies and represent a major global health burden. ESCC is the dominant histology globally but represents a minority of U.S. cases, with EAC accounting for the majority of U.S. cases. The patient outcomes for advanced ESCC and EAC are poor, and new therapeutic options are needed. Using a sensitive sequencing assay, we compared the genomic profiles of ESCC and EAC with attention to identification of therapeutically relevant genomic alterations. Methods. Next-generation sequencing-based comprehensive genomic profiling was performed on hybridization-captured, adaptor ligation-based libraries to a median coverage depth of >650× for all coding exons of 315 cancer-related genes plus selected introns from 28 genes frequently rearranged in cancer. Results from a single sample were evaluated for all classes of genomic alterations (GAs) including point mutations, short insertions and deletions, gene amplifications, homozygous deletions, and fusions/rearrangements. Clinically relevant genomic alterations (CRGAs) were defined as alterations linked to approved drugs and those under evaluation in mechanism-driven clinical trials. Results. There were no significant differences by sex for either tumor type, and the median age for all patients was 63 years. All ESCCs and EACs were at an advanced stage at the time of sequencing. All 71 ESCCs and 231 EACs featured GAs on profiling, with 522 GAs in ESCC (7.4 per sample) and 1,303 GAs in EAC (5.6 per sample). The frequency of clinically relevant GAs in ESCC was 94% (2.6 per sample) and 93% in EAC (2.7 per sample). CRGAs occurring more frequently in EAC included KRAS (23% EAC vs. 6% ESCC) and ERBB2 (23% EAC vs. 3% ESCC). ESCC samples were enriched for CRGA in PIK3CA (24% ESCC vs. 10% EAC), PTEN (11% ESCC vs. 4% EAC), and NOTCH1 (17% ESCC vs. 3% EAC). Other GAs that differed significantly between histologic

  12. Infection by human papillomavirus types 6, 11, 16, 18, 31, 33 and 35 of the cervix in Japanese women.

    PubMed

    Takahashi, Y.; Yamade, I.; Nakamura, T.; Akiyama, M.; Hayashi, Y.; Ishiguro, T.; Noda, Y.

    1995-01-01

    Exfoliated cervical cells from 321 Japanese women were examined for human papillomavirus (HPV) DNA types 6, 11, 16, 18, 31, 33 and 35 using polymerase chain reaction (PCR) and dot-blot hybridization methods. HPV DNA was present in 9.3% of patients with normal cervixes, 72.7% of patients with cervical intraepithelial neoplasia (CIN) and 77.8% of patients with invasive carcinoma. Younger patients (cervixes had a 18.5% incidence of HPV DNA, whilst similar older patients (>/=50 years) had a 1.9% incidence, a significant difference (chi2= 6.478, P < 0.01). In the CIN I and II groups, an incidence of 11.1% of types 16 and 18 was found, while in the CIN III or invasive carcinoma group the incidence was 58.1%, again a significant difference (chi2 = 12.075, P < 0.01). Furthermore, persistence or progression of CIN showed a significant correlation with infections by types 16 and 33 (chi2= 4.904, P < 0.01). However, no significantly different incidence of HPV infection was found between the CIN and the invasive carcinoma groups. It is suggested that (a) younger patients with normal cervixes have a higher incidence of HPV infection than do older patients; (b) HPV types 16, 18 and 33 are important etiologic agents of CIN III and invasive carcinoma, as well as in the persistence and progression of CIN; (c) progression of CIN to invasive carcinoma may depend on factors other than HPV infection in the cervix. PMID:11578452

  13. Injuries to the cervix in sexual trauma.

    PubMed

    Keller, Patricia; Nelson, Jenenne P

    2008-01-01

    Research on genital injury in sexual assault is limited and few articles have documented injuries to the cervix in sexual assault victims. This review focuses on reviewing and critically evaluating available literature on injuries of the cervix associated with rape, sexual trauma, and some other circumstances. Based on this evaluation, topics for future research are suggested. Nursing and medical studies were examined for this review. The collective studies date from 1991 to 2004. Although multiple articles were identified pertaining to sexual assault and genital injury, only six articles that specifically referred to injuries associated with genital and cervical tissue were included.

  14. Concomitant cetuximab and radiation therapy: A possible promising strategy for locally advanced inoperable non-melanoma skin carcinomas

    PubMed Central

    DELLA VITTORIA SCARPATI, GIUSEPPINA; PERRI, FRANCESCO; PISCONTI, SALVATORE; COSTA, GIUSEPPE; RICCIARDIELLO, FILIPPO; DEL PRETE, SALVATORE; NAPOLITANO, ALBERTO; CARRATURO, MARCO; MAZZONE, SALVATORE; ADDEO, RAFFAELE

    2016-01-01

    Non-melanoma skin cancers (NMSCs) include a heterogeneous group of malignancies arising from the epidermis, comprising squamous cell carcinoma (SCC), basal cell carcinoma (BCC), Merkel cell carcinoma and more rare entities, including malignant pilomatrixoma and sebaceous gland tumours. The treatment of early disease depends primarily on surgery. In addition, certain patients present with extensive local invasion or metastasis, which renders these tumours surgically unresectable. Improving the outcome of radiotherapy through the use of concurrent systemic therapy has been demonstrated in several locally advanced cancer-treatment paradigms. Recently, agents targeting the human epidermal growth factor receptor (EGFR) have exhibited a consolidated activity in phase II clinical trials and case series reports. Cetuximab is a monoclonal antibody that binds to and completely inhibits the EGFR, which has been revealed to be up-regulated in a variety of SCCs, including NMSCs. The present review aimed to summarize the role of anti-EGFR agents in the predominant types of NMSC, including SCC and BCC, and focuses on the cetuximab-based studies, highlighting the biological rationale of this therapeutic option. In addition, the importance of the association between cetuximab and radiotherapy for locally advanced NMSC is discussed. PMID:27073643

  15. Hypofractionated Radiation Therapy Followed by Surgery in Treating Patients With Advanced Squamous Cell Carcinoma of the Oral Cavity

    ClinicalTrials.gov

    2016-10-12

    Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Verrucous Carcinoma of the Oral Cavity; Tongue Cancer

  16. Budd-Chiari syndrome in urology: Impact on nephrectomy for advanced renal cell carcinoma

    PubMed Central

    Shirodkar, Samir P.; Soloway, Mark S.; Ciancio, Gaetano

    2011-01-01

    Objectives: Budd-Chiari syndrome (BCS) is a poorly understood entity in urology. It results from obstruction of the hepatic veins and the subsequent complications. It has been infrequently reported to be secondary to hepatic venous obstruction from invasion by an inferior vena cava (IVC) tumor thrombus in renal cell carcinoma (RCC). We report the largest known series of patients with RCC and BCS. Patients and Methods: Ten patients presented to a tertiary hospital with locally advanced RCC with IVC tumor thrombus. All were evaluated and had clinical or radiographic evidence of BCS. All underwent nephrectomy, IVC thrombectomy or ligation, and tumor removal from the hepatic veins. The perioperative and pathological factors were measured. These included estimated blood loss (EBL) and transfusions. Inpatient factors including duration of intubation, length of intensive care unit (ICU) stay, and overall length of stay (LOS) were recorded. The tumor-free status was evaluated. Results: The average age was 59 years. No intraoperative deaths occurred. Two intraoperative complications were noted. The mean EBL was 4244 cc; mean surgery length was 8 hours 12 minutes; and the mean ICU stay was nine days. The overall LOS averaged 13.25 days. One patient died postoperatively of sepsis and multisystem organ failure. One patient required reoperation for an abdominal wall hematoma caused by subcutaneous enoxaparin administration. Average follow-up was 28 months. Five patients are alive with no evidence of disease. Conclusions: Budd-Chiari syndrome is a rare entity in urology, with a potential for significant morbidity and mortality. Surgical excision of the primary tumor along with thrombectomy results in alleviation of BCS and improvement in the patient. PMID:22022058

  17. Combined sorafenib and yttrium-90 radioembolization for the treatment of advanced hepatocellular carcinoma

    PubMed Central

    Salman, A.; Simoneau, E.; Hassanain, M.; Chaudhury, P.; Boucher, L.M.; Valenti, D.; Cabrera, T.; Nudo, C.; Metrakos, P.

    2016-01-01

    Background and Aims In this pilot study, we assessed the safety and tolerability of combining sorafenib with 90Y radioembolization for the treatment of unresectable hepatocellular carcinoma (hcc). Methods The study, conducted prospectively during 2009–2012, included eligible patients with unresectable hcc and a life expectancy of at least 12 weeks. Each patient received sorafenib (400 mg twice daily) for 6–8 weeks before 90Y treatment. Safety and tolerability were assessed. Results Of the 40 patients enrolled, 29 completed treatment (combined therapy). In the initial cohort, the most common cause of hcc was hepatitis C (32.5%), and most patients were staged Child A (82.5%). The 29 patients who completed the study had similar baseline characteristics. Grades 1 and 2 toxicities accounted for 77.8% of all adverse events reported. The most common toxicities reported were fatigue (19.0%), alteration in liver function (7.9%), and diarrhea (6.3%). There were 12 grade 3 and 2 grade 4 toxicity events reported. One patient died of liver failure within 30 days after treatment. During the study, the sorafenib dose was reduced in 6 patients (20.7%), and sorafenib had to be interrupted in 4 patients (13.8%) and discontinued in 4 patients (13.8%). The disease control rate was 72.4% per the modified Response Evaluation Criteria in Solid Tumors, and tumour necrosis was observed in 82.8% of patients. Overall survival in patients undergoing combined therapy was 12.4 months. Conclusions Preliminary results demonstrate the safety and tolerability of combining 90Y radioembolization and sorafenib for advanced hcc. A larger prospective study is needed to determine the extent of the survival benefit. PMID:27803608

  18. Critical appraisal of pazopanib as treatment for patients with advanced metastatic renal cell carcinoma.

    PubMed

    Bukowski, Ronald M

    2011-01-01

    The management of renal cell carcinoma (RCC) has undergone significant changes during the past 10 years, with the treatment of metastatic RCC undergoing the most radical changes. These developments reflect an enhanced understanding of this tumor's underlying biology, which was then translated into the development of a new treatment paradigm. Current therapeutic approaches for the management of patients with metastatic RCC utilize knowledge of histology, molecular abnormalities, clinical prognostic factors, the natural history of this malignancy, and the treatment efficacy and toxicity of available agents. The treatment options available for patients with metastatic RCC have changed dramatically over the past 6 years. Interferon-α and interleukin-2 were the previous mainstays of therapy, but since December 2005, six new agents have been approved in the US for the treatment of advanced RCC. Three are multi-targeted tyrosine kinase inhibitors (TKI) including sunitinib, sorafenib, and pazopanib, two target the mammalian target of rapamycin (temsirolimus and everolimus), and one is a humanized monoclonal antibody (bevacizumab in combination with interferon-α). The current review focuses on the newest TKI available to treat patients with metastatic RCC, pazopanib. The development of this agent both preclinically and clinically is reviewed. The efficacy and safety data from the pivotal clinical trials are discussed, and the potential role of pazopanib in the treatment of patients with metastatic RCC in comparison to other treatment alternatives is critically appraised. This agent has a favorable overall risk benefit, and the available data demonstrate efficacy in patients with metastatic RCC who are either treatment-naïve or cytokine refractory. It therefore represents another alternative for treatment of metastatic RCC patients.

  19. Sequence of treatment in locally advanced and metastatic renal cell carcinoma

    PubMed Central

    Fischer, Stefanie; Gillessen, Silke

    2015-01-01

    The spectrum of drugs that have shown activity in advanced or metastatic renal cell carcinoma (RCC) has led to a debate on the optimal sequence of treatments. There is agreement on recommending targeted agents as the standard of care in this disease. Uncertainty, however, remains on the best first-line drug choice. Physicians and patients may select sunitinib, bevacizumab in combination with interferon-alpha (IFN-α), pazopanib, or—in poor risk patients—temsirolimus. There are also a variety of therapies with proven efficacy on hand in the second-line setting: sorafenib, pazopanib, axitinib, and everolimus. While most randomized RCC trials assessed progression free survival (PFS) as primary endpoint, some agents were shown to improve median overall survival (OS), and given in sequence they have extended the life expectancy of RCC patients from 13 months in the cytokine era to over 30 months. Despite the progress made, there are sobering aspects to the oncologic success story in RCC, as the new treatments do not obtain an objective response or disease stabilization (SD) in all patients. There are also as yet no predictors to select patients who might benefit and those who are primary resistant to specific drugs, and ultimately almost all patients will experience disease progression. Bearing inevitable treatment failure in mind, availability of further drugs and switching therapy while the patient is in a condition to continue pharmacotherapy is essential. Of note, depending on the setting, only 33-59% of patients receive second-line treatment. In this review we present data on first-, second-, and third-line treatment in RCC, and discuss the difficulties in their interpretation in the context of treatment sequence. We summarize biological aspects and discuss mechanisms of resistance to anti-angiogenic therapy and their implications for treatment selection. PMID:26816832

  20. Hypofractionated radiotheapy using helical tomotherapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis

    PubMed Central

    2013-01-01

    Background We want to evaluate the efficacy of helical tomotherapy (HT) for treating advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). Methods We treated 35 patients for unresectable HCC combined with PVTT in whom other treatment modalities were not indicated. The tumor thrombi involved the main trunk of the portal vein in 18 patients (51.4%) and the first or second order branches in 17 patients (48.6%). A median dose of 50 Gy (range: 45–60 Gy) was delivered in 10 fractions. Capecitabine was given concomitantly at a dose of 600 mg/m2 twice daily during radiotherapy. Results The responses were evaluated via computed tomography. There was a complete response (CR) in 5 patients (14.3%), partial response (PR) in 10 patients (28.6%), stable disease (SD) in 18 patients (51.4%) and progressive disease (PD) in 2 patients (5.7%). The Child-Pugh classification (A vs B) and the Japan integrated staging (JIS) score (2 vs 3) were statistically significant parameters that predicted the response of PVTT (p = 0.010 and p = 0.026, respectively). The median survival, one and two year survival rate of all patients was 12.9 months, 51.4% and 22.2%, respectively. The patients with tumor thrombi in the main portal trunk showed statistically inferior overall survival than patients with tumor thrombi in the portal vein branches (9.8 versus 16.6 months, respectively, p = 0.036). The responders’ median survival was 13.9 months, double 6.9 months as the median survival of the non-responders. No radiation induced liver disease or treatment related mortality was not appeared. Conclusions Hypofractionated radiotherapy with HT was effective not only for tumor response but also for survival in the advanced HCC patients with PVTT. And stricter patient selection by Child-Pugh classification and JIS score may maximize the potential benefits of this treatment. PMID:23324259

  1. Chinese Herbal Formulation PHY906 and Sorafenib Tosylate in Treating Patients With Advanced Liver Cancer

    ClinicalTrials.gov

    2016-06-17

    Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Advanced Adult Hepatocellular Carcinoma; BCLC Stage B Adult Hepatocellular Carcinoma; BCLC Stage C Adult Hepatocellular Carcinoma

  2. Efficacy and safety of the oxaliplatin-based chemotherapy in the treatment of advanced primary hepatocellular carcinoma

    PubMed Central

    Liu, Lin; Zheng, Ying-hui; Han, Li; Qin, Shu-Kui

    2016-01-01

    Abstract Background: Many clinical studies have demonstrated the survival benefits of oxaliplatin-based chemotherapy for advanced hepatocellular carcinoma patients. Therefore, we aim to evaluate the efficacy and safety of oxaliplatin-based chemotherapy in patients with advanced hepatocellular carcinoma by conducting a meta-analysis of prospective studies. Methods: A comprehensive literature search was performed using the PubMed, Cochrane Library, EMBASE, and Web of Science databases from their inception to June 2016. Only prospective studies evaluating oxaliplatin-based chemotherapy in patients with advanced hepatocellular carcinoma were selected. The main outcomes included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and main adverse events. Results: Ten prospective studies involving 525 patients were included. The pooled ORR, 1-year PFS, and OS were 14.4% (95% confidence interval [CI] 9.2–19.6%), 9.3% (95%CI 10–28%), and 35.7% (95%CI 27–44%), respectively, for oxaliplatin-based chemotherapy. The median PFS and OS were 4.7 and 9.4 months, respectively. The incidences of grade 3/4 toxicities of neutropenia, thrombopenia, anemia, neurotoxicity, diarrhea, and nausea/vomiting were 17.2%, 9.2%, 6.0%, 4.8%, 3.1%, and 1.8%, respectively. Subgroup analysis revealed that the pooled ORR was 13.9% (95%CI 6.8–21%) in Asian patients and 12.8% (95%CI 6.8–18.7%) in Western patients. For Asian patients, the median PFS and OS were 4.2 and 9.2 months, and the 1-year PFS and OS were 12.5% and 30.5%, respectively. For Western patients, the median PFS and OS were 4.7 and 9.5 months, and the 1-year PFS and OS were 19.6% and 42.4%, respectively. There were no significant differences in the ORR, 1-year PFS, and OS (P > 0.05) between Asian and Western patients. Conclusions: Oxaliplatin-based chemotherapy appears to be effective and safe for the treatment of advanced hepatocellular carcinoma. PMID:27749557

  3. Long-term outcomes of patients with advanced hepatocellular carcinoma who achieved complete remission after sorafenib therapy

    PubMed Central

    2015-01-01

    Background/Aims Sorafenib is currently the sole molecular targeted agent that improves overall survival in advanced hepatocellular carcinoma (HCC). Despite the efficacy of sorafenib, the response rate varies in patients with advanced HCC. We retrospectively analyzed a series of Korean patients with advanced HCC with complete remission (CR) after sorafenib therapy. Methods In total, 523 patients with advanced HCC were treated with sorafenib in 3 large tertiary referral hospitals in Korea. A survey was conducted to collect data on patients who experienced CR after sorafenib monotherapy, and their medical records and follow-up data were analyzed. The tumor response and recurrence rates were assessed by radiologic study, based on modified response evaluation criteria in solid tumors. Results Seven patients with advanced HCC experienced CR after sorafenib therapy. The median time to tumor disappearance and the median disease-free survival time were 3 months and 9 months, respectively. HCC recurrence was identified in three cases (42.9%). Of these, two patients discontinued sorafenib before or after achieving CR and the other patient continued sorafenib after achieving CR. HCC recurred at 3, 10, and 42 months after CR in these three patients. Three patients needed dose reduction for toxicity and adverse events. Conclusions Though CR was achieved after sorafenib therapy in patients with advanced HCC, the recurrence rate was relatively high. Subsequent strategies to reduce a chance of recurrence after sorafenib therapy are required to investigate. PMID:26527250

  4. Locally Advanced Stage High-Grade Mucoepidermoid Carcinoma of Salivary Gland in a 9-Year-Old Girl: The Controversy of Adjuvant Therapy

    PubMed Central

    Martínez, Olga Micol; Dorado, Elena Daghoum; García, María Dolores Amorós; Ramírez, María Isabel Oviedo; de la Fuente Muñoz, Isabel; Soler, Jose Luis Fuster

    2016-01-01

    Malignant salivary gland tumors are rare in children, mostly represented by low-grade mucoepidermoid carcinomas. For these patients, long-term survival rates above 95% are reported after surgical resection. Here we report a case of a 9-year-old girl with a high grade locally advanced mucoepidermoid carcinoma undergoing adjuvant radiotherapy and chemotherapy after surgery. We emphasize the controversy and lack of evidence-based indication for these highly toxic adjuvant therapy modalities in children. PMID:27746885

  5. [Survival after Sorafenib Treatment for Advanced Recurrent Hepatocellular Carcinoma with Tumor Thrombus in the Inferior Vena Cava].

    PubMed

    Matoba, Hideaki; Seta, Shinsuke

    2015-11-01

    A 72-year-old man with chronic viral hepatitis type B undergoing surgery for hepatocellular carcinoma was found to have a recurrent tumor in the left liver with peritoneal dissemination near the inferior vena cava(IVC)and tumor thrombus in the IVC. For this patient diagnosed with Barcelona clinic liver cancer (BCLC) classification stage C hepatocellular carcinoma, we initiated 800 mg/body sorafenib. Two weeks after the initiation of sorafenib, the patient experienced grade 3 hand-foot syndrome, after which, the dose of sorafenib was reduced to 400 mg/body. After 1 year, CT showed an enlarged tumor in the left liver and multiple metastases to the lung. However, no remarkable difference was observed in the peritoneal dissemination and the tumor thrombus. He has been receiving sorafenib for 19 months with a good quality of life. Sorafenib can be provided on an outpatient basis and it may facilitate long-term survival for patients with advanced recurrent hepatocellular carcinoma with IVC tumor thrombus. This clinical condition is very rare, and the standard treatment for it still has not been established.

  6. [Survival after Sorafenib Treatment for Advanced Recurrent Hepatocellular Carcinoma with Tumor Thrombus in the Inferior Vena Cava].

    PubMed

    Matoba, Hideaki; Seta, Shinsuke

    2015-11-01

    A 72-year-old man with chronic viral hepatitis type B undergoing surgery for hepatocellular carcinoma was found to have a recurrent tumor in the left liver with peritoneal dissemination near the inferior vena cava(IVC)and tumor thrombus in the IVC. For this patient diagnosed with Barcelona clinic liver cancer (BCLC) classification stage C hepatocellular carcinoma, we initiated 800 mg/body sorafenib. Two weeks after the initiation of sorafenib, the patient experienced grade 3 hand-foot syndrome, after which, the dose of sorafenib was reduced to 400 mg/body. After 1 year, CT showed an enlarged tumor in the left liver and multiple metastases to the lung. However, no remarkable difference was observed in the peritoneal dissemination and the tumor thrombus. He has been receiving sorafenib for 19 months with a good quality of life. Sorafenib can be provided on an outpatient basis and it may facilitate long-term survival for patients with advanced recurrent hepatocellular carcinoma with IVC tumor thrombus. This clinical condition is very rare, and the standard treatment for it still has not been established. PMID:26805098

  7. [The correlation between cytology and histopathology of primary adenocarcinoma of the uterine cervix].

    PubMed

    Chen, S R; Chang, M C; Ho, W L

    1994-05-01

    Cytodiagnosis is a simple, non-invasive and economical screening method for uterine cervical malignancy. Adenocarcinoma as a primary tumor of uterine cervix, although relatively rare, is increasing recently. The first part of the study consisted of 113 patients, seen during a 10-year period, with adenocarcinoma of the uterine cervix proven by tissue diagnosis with prior and/or coincident Papanicolaou smears available in our hospital. Their cytology were as follows: positive/suspicious for adenocarcinoma in 72 cases (63.7%) and incorrect diagnosis for adenocarcinoma in 41 cases (36.3%). These included epidermoid carcinoma, 21 cases (18.6%); atypia, 8 cases (7.1%); negative smears, 8 cases (7.1%); inadequate specimens, 3 cases (2.7%) and radiation effect, 1 case (0.8%). The second part of the study is concerned with the 82 cases whose smear diagnosis was adenocarcinoma in the same period. The results of their tissue diagnosis and accuracy were as follows: adenocarcinoma in 62 cases (75.6%); epidermoid carcinoma in 9 and epidermoid carcinoma in situ in 3 cases totalling 12 cases (14.6%); and false positive in 8 cases (9.8%). The cytomorphology and its correlation to underdiagnosis and overdiagnosis is discussed. Our data revealed that cervicovaginal smears served as a routine for the screening of primary adenocarcinoma of the uterine cervix and for follow-up and detection of recurrence. In order to increase the accuracy, screening cytotechnicians and cytopathologists should acquaint themselves with the morphology of cervical adenocarcinoma by comparing cervicovaginal smear with histopathology.

  8. Intratumoral PV701 in Treating Patients With Advanced or Recurrent Unresectable Squamous Cell Carcinoma of the Head and Neck

    ClinicalTrials.gov

    2013-01-23

    Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Salivary Gland Squamous Cell Carcinoma; Stage III Salivary Gland Cancer; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IV Salivary Gland Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity

  9. State of the art: diagnostic tools and innovative therapies for treatment of advanced thymoma and thymic carcinoma.

    PubMed

    Ried, Michael; Marx, Alexander; Götz, Andrea; Hamer, Okka; Schalke, Berthold; Hofmann, Hans-Stefan

    2016-06-01

    In this review article, state-of-the-art diagnostic tools and innovative treatments of thymoma and thymic carcinoma (TC) are described with special respect to advanced tumour stages. Complete surgical resection (R0) remains the standard therapeutic approach for almost all a priori resectable mediastinal tumours as defined by preoperative standard computed tomography (CT). If lymphoma or germ-cell tumours are differential diagnostic considerations, biopsy may be indicated. Resection status is the most important prognostic factor in thymoma and TC, followed by tumour stage. Advanced (Masaoka-Koga stage III and IVa) tumours require interdisciplinary therapy decisions based on distinctive findings of preoperative CT scan and ancillary investigations [magnetic resonance imaging (MRI)] to select cases for primary surgery or neoadjuvant strategies with optional secondary resection. In neoadjuvant settings, octreotide scans and histological evaluation of pretherapeutic needle biopsies may help to choose between somatostatin agonist/prednisolone regimens and neoadjuvant chemotherapy as first-line treatment. Finally, a multimodality treatment regime is recommended for advanced and unresectable thymic tumours. In conclusion, advanced stage thymoma and TC should preferably be treated in experienced centres in order to provide all modern diagnostic tools (imaging, histology) and innovative therapy techniques. Systemic and local (hyperthermic intrathoracic chemotherapy) medical treatments together with extended surgical resections have increased the therapeutic options in patients with advanced or recurrent thymoma and TC.

  10. Efficacy of short-term nivolumab treatment in a Chinese patient with relapsed advanced-stage lung squamous cell carcinoma

    PubMed Central

    Pi, Guoliang; He, Hanping; Bi, Jianping; Li, Ying; Li, Yanping; Zhang, Yong; Wang, Mingwei; Han, Guang; Lin, Chi

    2016-01-01

    Abstract Introduction: Currently, the options are limited for the treatment of patients who have failed 2 lines of chemotherapy for advanced lung squamous cell carcinoma (SCC). Recently, nivolumab, a fully human IgG4 programmed death 1 immune checkpoint inhibitor antibody, was approved to treat patients with advanced stage, relapsed/refractory lung SCC. Although nivolumab has demonstrated antitumor activity with survival benefit in Caucasian patients, its efficacy in Asian patients is unknown. Case Report: In this report, we describe a Chinese patient with relapsed advanced stage lung SCC who had an excellent response to nivolumab after only 2 doses without any adverse effects. Immunohistochemical analysis indicated the tumor was stained positive for programmed death-ligand 1. Conclusion: To our knowledge, this is the first report of satisfactory efficacy of short-term nivolumab treatment in a Chinese patient with relapsed advanced-stage lung SCC. Further clinical trials in Asian countries are needed to test whether nivolumab immunotherapy is a safe and effective treatment for Asian patients with lung SCC. PMID:27749580

  11. Local dynamic changes of the cervix associated with incompetent cervix before and after Shirodkar's operation.

    PubMed

    Kikuchi, A; Kozuma, S; Marumo, G; Machida, Y; Yano, T; Taketani, Y

    1998-09-01

    A 31-year-old woman, gravida 2 para 1, visited our clinic for routine follow-up at 20 weeks' gestation. Although she had no abdominal pain or pressure, digital vaginal examination revealed dilatation of the internal cervical os of 1.5 cm, and transvaginal sonography demonstrated dynamic changes in the shape of the cervical canal. The patient underwent Shirodkar's operation. Routine postoperative assessment of the cervix with transvaginal sonography showed dynamic dilatation of the upper cervix (above the cerclage), which was accompanied by a sensation of pelvic pressure but no apparent uterine contractions. A healthy male infant weighing 2,980 g was delivered at 38 weeks' gestation. PMID:9719989

  12. Loss of MTUS1/ATIP expression is associated with adverse outcome in advanced bladder carcinomas: data from a retrospective study

    PubMed Central

    2014-01-01

    Background Seventy percent of all bladder tumours tend to recur and need intensive surveillance, and a subset of tumours progress to muscle-invasive and metastatic disease. However, it is still difficult to find the adequate treatment for every individual patient as it is a very heterogeneous disease and reliable biomarkers are still missing. In our study we searched for new target genes in the critical chromosomal region 8p and investigated the potential tumour suppressor gene candidate MTUS1/ATIP in bladder cancer. Methods MTUS1 was identified to be the most promising deleted target gene at 8p in aCGH analysis with 19 papillary bladder tumours. A correlation with bladder cancer was further validated using immunohistochemistry of 85 papillary and 236 advanced bladder tumours and in functional experiments. Kaplan-Meier analysis and multivariate Cox-regression addressed overall survival (OS) and disease-specific survival (DSS) as a function of MTUS1/ATIP expression. Bivariate correlations investigated associations between MTUS1/ATIP expression, patient characteristics and histopathology. MTUS1 expression was analysed in cell lines and overexpressed in RT112, where impact on viability, proliferation and migration was measured. Results MTUS1 protein expression was lost in almost 50% of all papillary and advanced bladder cancers. Survival, however, was only influenced in advanced carcinomas, where loss of MTUS1 was associated with adverse OS and DSS. In this cohort, there was also a significant correlation of MTUS1 expression and histological subtype: positive expression was detected in all micropapillary tumours and aberrant nuclear staining was detected in a subset of plasmocytoid urothelial carcinomas. MTUS1 was expressed in all investigated bladder cell lines and overexpression in RT112 led to significantly decreased viability. Conclusions MTUS1 is a tumour suppressor gene in cultured bladder cancer cells and in advanced bladder tumours. It might represent one new

  13. Cancer of the uterine cervix and screening of Aboriginal women.

    PubMed

    Guest, C; Mitchell, H; Plant, A

    1990-08-01

    Carcinoma of the cervix has not been widely reported as an important health problem for Aboriginal women. From four sources, we have studied cervical cancer death rates, abnormalities detected by cervical cytology screening, and the proportion of women who had been screened. First, from the Northern Territory for the years 1979-1983, we present a relative risk of 6.3 (95% confidence interval, 3.0-11.6) for cervical cancer deaths in Aboriginal women compared with all Australian women. Second, the screening and disease rates in Aboriginal women were profiled within a large laboratory in Victoria. Since 1984, a fourfold increase in the number of smears taken at Aboriginal health services is apparent. In women attending these services, a high rate of significantly abnormal smears is evident. Third, to study the extent of screening, we interviewed Aboriginal women in a Victorian country setting and fourth, we examined a random sample of medical records from an Aboriginal Health Service. The proportion screened at least once rose from 5/47 (11%) among women whose most recent consultation with the Health Service was during the years 1974-1980 to 51/170 (31%) women who attended from 1981-1987 (p less than 0.01). Aboriginal communities may interpret these trends favourably as they encourage their women to be screened regularly to reduce cervical cancer mortality. PMID:2256865

  14. NCCN Task Force Report: Optimizing Treatment of Advanced Renal Cell Carcinoma With Molecular Targeted Therapy

    PubMed Central

    Hudes, Gary R.; Carducci, Michael A.; Choueiri, Toni K.; Esper, Peg; Jonasch, Eric; Kumar, Rashmi; Margolin, Kim A.; Michaelson, M. Dror; Motzer, Robert J.; Pili, Roberto; Roethke, Susan; Srinivas, Sandy

    2015-01-01

    The outcome of patients with metastatic renal cell carcinoma has been substantially improved with administration of the currently available molecularly targeted therapies. However, proper selection of therapy and management of toxicities remain challenging. NCCN convened a multidisciplinary task force panel to address the clinical issues associated with these therapies in attempt to help practicing oncologists optimize patient outcomes. This report summarizes the background data presented at the task force meeting and the ensuing discussion. PMID:21335444

  15. [Preoperative concurrent chemotherapy and radiation therapy in cervix cancer: preliminary results].

    PubMed

    Kochbati, Lotfi; Ben Ammar, Chiraz Nasr; Benna, Farouk; Hechiche, Monia; Boussen, Hamouda; Besbes, Mounir; Ben Abdallah, Mansour; Rahal, Khaled; Ben Ayed, Farhat; Ben Romdhane, Khaked; Maalej, Mongi

    2005-03-01

    This is a retrospective study of patients treated for cervix cancer staged IB2, IIA or IIB with bulky tumor (> 4cm). Treatment was concurrent radiotherapy (45Gy with 1,8Gy daily fraction) and chemotherapy (5 cycles of Platinum 40mg/m2/week). All patients underwent Brachytherapy (15Gy on the reference isodose according to Paris system) followed by surgery (radical abdominal hysterectomy and bilateral pelvic lymphadenectomy: Piver 3) Between October 1999 and December 2002, forty five patients were treated in this protocol. Median age was 46 years (21- 68). Histology was squamous cell carcinoma in 93% and glandular carcinoma in 7%. Average external radiation dose was 44Gy (20-50). Ninety three percent of patients had at least 3 cycles of chemotherapy and 46,5% received the planned 5 cycles. On the operative specimens, there was 62,5% complete response and only 7 pelvic node involvement (17,5%). Four postoperative complications were noted (one vascular injury, one urinary fistula, one phlebitis and one lymph collection). Preoperative combined radiotherapy and chemotherapy in the early bulky stages of uterine cervix cancer is well tolerated and "gives" a high rate of sterilisation. There was no increase in surgical morbidity.

  16. Feasibility and Response of Concurrent Weekly Docetaxel with Radical Radiotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma

    PubMed Central

    I, Rajesh; B, Rajesh; B, Selvamani; John, Subhashini

    2015-01-01

    Objective: (1) To study the feasibility, adverse effects and response of concurrent weekly Docetaxel with radical radiotherapy in inoperable locally advanced head and neck squamous cell carcinoma. (2) To assess the compliance and tolerance of weekly Docetaxel with radiotherapy. Material and Methods: Twenty one patients with stage III and IV head and neck squamous cell carcinoma satisfying inclusion criteria were selected and treated with conventional external radiotherapy of 70Gy in 35 fractions with weekly concurrent Docetaxel (15mg/sqm), administered one hour before radiotherapy. Assessment of toxicities and evaluationof response was carried out. Results: Majority of patients had stage IV diseaseand 17/21 (81%) received the planned radiotherapydose of 70Gy and ≥4 cycles of weekly chemotherapy. Duration of treatment ranged from 7.1to 11.2 weeks. The toxicities noted were Grade III mucositis in 57% and grade III skin reaction in 23%, grade III dysphagia in 38% and grade II weight loss in 23% of patients. Systemic toxicities associated with chemotherapy were minimal and there was no dose limiting toxicities. The overall locoregional response at first follow up was 85%, with complete response of 70% and partial response of 15%. Conclusion: Concurrent Docetaxel is a feasible and suitable alternate to Cisplatin and 5-Fluorouracil chemotherapy with good patient compliance. The late toxicities and survival need to be followed up. PMID:25954690

  17. Hsp90 Inhibitor AT13387 in Treating Patients With Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck Receiving Radiation Therapy and Cisplatin

    ClinicalTrials.gov

    2016-10-05

    Human Papillomavirus Infection; Stage III Hypopharyngeal Squamous Cell Carcinoma; Stage III Laryngeal Squamous Cell Carcinoma; Stage III Oral Cavity Squamous Cell Carcinoma; Stage III Oropharyngeal Squamous Cell Carcinoma; Stage IVA Hypopharyngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Squamous Cell Carcinoma; Stage IVA Oral Cavity Squamous Cell Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma; Stage IVB Hypopharyngeal Squamous Cell Carcinoma; Stage IVB Laryngeal Squamous Cell Carcinoma; Stage IVB Oral Cavity Squamous Cell Carcinoma; Stage IVB Oropharyngeal Squamous Cell Carcinoma

  18. Copper and zinc levels in serum from patients with abnormalities of the uterine cervix.

    PubMed

    Grail, A; Norval, M

    1986-01-01

    Serum copper and zinc levels were determined by atomic absorption spectroscopy in 110 women with varying degrees of cervical dysplasia up to carcinoma-in-situ and in 9 women with invasive carcinoma of the cervix, and compared with levels in 21 women with no evidence of cervical dysplasia. The average serum copper and zinc levels in the control group were 1.25 mg/l and 1.02 mg/l (respectively). The mean serum copper level increased with dysplasia to 1.4 mg/l and with invasive carcinoma to 1.47 mg/l. The mean serum zinc levels were decreased in cervical intra-epithelial neoplasia (CIN) grade 1 to 0.81 mg/l and in invasive carcinoma to 0.73 mg/l. The copper:zinc ratios varied significantly between controls, patients with cervical dysplasia and patients with invasive carcinoma (p less than 0.01). Measurement of serum ceruloplasmin revealed no significant differences among the control group and the groups of patients.

  19. Novel Pretreatment Scoring Incorporating C-reactive Protein to Predict Overall Survival in Advanced Hepatocellular Carcinoma with Sorafenib Treatment

    PubMed Central

    Nakanishi, Hiroyuki; Kurosaki, Masayuki; Tsuchiya, Kaoru; Yasui, Yutaka; Higuchi, Mayu; Yoshida, Tsubasa; Komiyama, Yasuyuki; Takaura, Kenta; Hayashi, Tsuguru; Kuwabara, Konomi; Nakakuki, Natsuko; Takada, Hitomi; Ueda, Masako; Tamaki, Nobuharu; Suzuki, Shoko; Itakura, Jun; Takahashi, Yuka; Izumi, Namiki

    2016-01-01

    Objectives This study aimed to build a prediction score of prognosis for patients with advanced hepatocellular carcinoma (HCC) after sorafenib treatment. Methods A total of 165 patients with advanced HCC who were treated with sorafenib were analyzed. Readily available baseline factors were used to establish a scoring system for the prediction of survival. Results The median survival time (MST) was 14.2 months. The independent prognostic factors were C-reactive protein (CRP) <1.0 mg/dL [hazard ratio (HR) =0.51], albumin >3.5 g/dL (HR =0.55), alpha-fetoprotein <200 ng/mL (HR =0.45), and a lack of major vascular invasion (HR =0.39). Each of these factors had a score of 1, and after classifying the patients into five groups, the total scores ranged from 0 to 4. Higher scores were linked to significantly longer survival (p<0.0001). Twenty-nine patients (17.6%) with a score of 4 had a MST as long as 36.5 months, whereas MST was as short as 2.4 and 3.7 months for seven (4.2%) and 22 (13.3%) patients with scores of 0 and 1, respectively. Conclusions A novel prognostic scoring system, which includes the CRP level, has the ability to stratify the prognosis of patients with advanced stage HCC after treatment with sorafenib. PMID:27781198

  20. A Phase I Dose-Finding Study of Silybin Phosphatidylcholine (Milk Thistle) in Patients With Advanced Hepatocellular Carcinoma

    PubMed Central

    Siegel, Abby B.; Narayan, Rupa; Rodriguez, Rosa; Goyal, Abhishek; Jacobson, Judith S.; Kelly, Kara; Ladas, Elena; Lunghofer, Paul J.; Hansen, Ryan J.; Gustafson, Daniel L.; Flaig, Thomas W.; Tsai, Wei Yann; Wu, David P. H.; Lee, Valerie; Greenlee, Heather

    2013-01-01

    Purpose To determine the maximum tolerated dose per day of silybin phosphatidylcholine (Siliphos) in patients with advanced hepatocellular carcinoma (HCC) and hepatic dysfunction. Experimental Design Patients with advanced HCC not eligible for other therapies based on poor hepatic function were enrolled in a phase I study of silybin phosphatidylcholine. A standard phase I design was used with 4 planned cohorts, dose escalating from 2, 4, 8, to 12 g per day in divided doses for 12 weeks. Results Three participants enrolled in this single institution trial. All enrolled subjects consumed 2 g per day of study agent in divided doses. Serum concentrations of silibinin and silibinin glucuronide increased within 1 to 3 weeks. In all 3 patients, liver function abnormalities and tumor marker α-fetoprotein progressed, but after day 56 the third patient showed some improvement in liver function abnormalities and inflammatory biomarkers. All 3 participants died within 23 to 69 days of enrolling into the trial, likely from hepatic failure, but it could not be ruled out that deaths were possibly due to the study drug. Conclusion Short-term administration of silybin phosphatidylcholine in patients with advanced HCC resulted in detectable increases in silibinin and its metabolite, silibinin glucuronide. The maximum tolerated dose could not be established. Since patients died soon after enrollment, this patient population may have been too ill to benefit from an intervention designed to improve liver function tests. PMID:23757319

  1. Ultra-deep targeted sequencing of advanced oral squamous cell carcinoma identifies a mutation-based prognostic gene signature

    PubMed Central

    Huang, Po-Jung; Huang, Yi; Hsu, An; Tang, Petrus; Chang, Yu-Sun; Chen, Hua-Chien; Yen, Tzu-Chen

    2015-01-01

    Background Patients with advanced oral squamous cell carcinoma (OSCC) have heterogeneous outcomes that limit the implementation of tailored treatment options. Genetic markers for improved prognostic stratification are eagerly awaited. Methods Herein, next-generation sequencing (NGS) was performed in 345 formalin-fixed paraffin-embedded (FFPE) samples obtained from advanced OSCC patients. Genetic mutations on the hotspot regions of 45 cancer-related genes were detected using an ultra-deep (>1000×) sequencing approach. Kaplan-Meier plots and Cox regression analyses were used to investigate the associations between the mutation status and disease-free survival (DFS). Results We identified 1269 non-synonymous mutations in 276 OSCC samples. TP53, PIK3CA, CDKN2A, HRAS and BRAF were the most frequently mutated genes. Mutations in 14 genes were found to predict DFS. A mutation-based signature affecting ten genes (HRAS, BRAF, FGFR3, SMAD4, KIT, PTEN, NOTCH1, AKT1, CTNNB1, and PTPN11) was devised to predict DFS. Two different resampling methods were used to validate the prognostic value of the identified gene signature. Multivariate analysis demonstrated that presence of a mutated gene signature was an independent predictor of poorer DFS (P = 0.005). Conclusions Genetic variants identified by NGS technology in FFPE samples are clinically useful to predict prognosis in advanced OSCC patients. PMID:25980437

  2. Shape priors for segmentation of the cervix region within uterine cervix images.

    PubMed

    Lotenberg, Shelly; Gordon, Shiri; Greenspan, Hayit

    2009-06-01

    The work focuses on a unique medical repository of digital uterine cervix images ("cervigrams") collected by the National Cancer Institute (NCI), National Institute of Health, in longitudinal multiyear studies. NCI together with the National Library of Medicine is developing a unique web-based database of the digitized cervix images to study the evolution of lesions related to cervical cancer. Tools are needed for the automated analysis of the cervigram content to support the cancer research. In recent works, a multistage automated system for segmenting and labeling regions of medical and anatomical interest within the cervigrams was developed. The current paper concentrates on incorporating prior-shape information in the cervix region segmentation task. In accordance with the fact that human experts mark the cervix region as circular or elliptical, two shape models (and corresponding methods) are suggested. The shape models are embedded within an active contour framework that relies on image features. Experiments indicate that incorporation of the prior shape information augments previous results.

  3. Shape priors for segmentation of the cervix region within uterine cervix images

    NASA Astrophysics Data System (ADS)

    Lotenberg, Shelly; Gordon, Shiri; Greenspan, Hayit

    2008-03-01

    The work focuses on a unique medical repository of digital Uterine Cervix images ("Cervigrams") collected by the National Cancer Institute (NCI), National Institute of Health, in longitudinal multi-year studies. NCI together with the National Library of Medicine is developing a unique web-based database of the digitized cervix images to study the evolution of lesions related to cervical cancer. Tools are needed for the automated analysis of the cervigram content to support the cancer research. In recent works, a multi-stage automated system for segmenting and labeling regions of medical and anatomical interest within the cervigrams was developed. The current paper concentrates on incorporating prior-shape information in the cervix region segmentation task. In accordance with the fact that human experts mark the cervix region as circular or elliptical, two shape models (and corresponding methods) are suggested. The shape models are embedded within an active contour framework that relies on image features. Experiments indicate that incorporation of the prior shape information augments previous results.

  4. Cancer cervix -- a retrospective study.

    PubMed

    Kamaluddin, M

    1999-06-01

    This retrospective study determined the proportion of cervical cancer among female cancer patients attending the radiotherapy department of Mymensingh Medical College Hospital (MMCH), Bangladesh, and explored some of the predisposing factors relating to a high proportion of this disease. The study was conducted among 242 patients suffering from cervical cancer drawn from the 964 female patients managed at MMCH. The proportion of cervical cancer was quite high, mostly among women of low socioeconomic status. The majority of the patients was aged 15-44 years; 64% were married before 20 years of age, experiencing sexual activity and becoming pregnant earlier. About 58% of respondents had more than 4 pregnancies and 57% were of low socioeconomic class. About 65% of the cases presented with an advanced stage of cervical cancer and were managed palliatively, while 35% of the cases were at an early stage and treatment was intended to cure. The proportion of cervical cancer was higher in Hindu women than in Muslim women. In summary, factors such as early sexual activity, having the first child at a young age, multiple pregnancies, multiple sex partners, and poor genital hygiene were commonly the predisposing factors for cervical cancer. Recommended interventions are aimed at addressing these predisposing factors.

  5. Asian consensus workshop report: expert consensus guideline for the management of intermediate and advanced hepatocellular carcinoma in Asia.

    PubMed

    Han, Kwang-Hyub; Kudo, Masatochi; Ye, Sheng-Long; Choi, Jong Young; Poon, Roonni Tung-Ping; Seong, Jinsil; Park, Joong-Won; Ichida, Takafumi; Chung, Jin Wook; Chow, Pierce; Cheng, Ann-Lii

    2011-01-01

    Hepatocellular carcinoma (HCC) is a highly prevalent disease in many Asian countries, accounting for 80% of victims worldwide. Screening programs improve the detection of early HCC and have a positive impact on survival, but the majority of HCC patients in Asia still present with advanced stage disease. The treatment outcomes of HCC are affected by multiple variables, including liver function, performance status of the patient, and tumor stage. Therefore, it is not easy to apply a multidisciplinary therapeutic approach for optimal management. At present, limited numbers of HCC patients are eligible for curative therapies such as surgery or ablation in Asia. Therefore, most patients are eligible for only palliative treatments. For optimal management, the treatment choice is guided by staging systems and treatment guidelines. Numerous staging systems have been proposed and treatment guidelines vary by region. According to the Barcelona Clinic Liver Cancer (BCLC) guideline based on evidence from randomized clinical trials, only transarterial chemoembolization (TACE) is recommended for intermediate stage HCC and sorafenib for advanced stage HCC. However, treatment guidelines from Asian countries have adopted several other therapeutic modalities such as a surgical approach, hepatic arterial infusion chemotherapy, external radiation, and their combinations based on clinical experiences for intermediate and advanced stage HCC. Although TACE is the main therapeutic modality in the intermediate stage, overall therapeutic outcomes depend on the tumor size. In the advanced stage, the prognosis depends on the tumor status, e.g. major vessel invasion or extrahepatic spread. Thus, a new staging system representing prognoses suitable for Asian HCC patients and a corresponding optimal treatment algorithm should be further investigated using evidence-based data, which will finally bring about an Asian consensus for the management of intermediate and advanced stage HCC.

  6. Impact of Adding Concomitant Chemotherapy to Hyperfractionated Accelerated Radiotherapy for Advanced Head-and-Neck Squamous Cell Carcinoma

    SciTech Connect

    Nuyts, Sandra Dirix, Piet; Clement, Paul M.J.; Poorten, Vincent Vander; Delaere, Pierre; Schoenaers, Joseph; Hermans, Robert; Bogaert, Walter van den

    2009-03-15

    Purpose: To evaluate the feasibility and efficacy of a hyperfractionated accelerated radiotherapy (RT) schedule combined with concomitant chemotherapy (Cx) in patients with locally advanced head-and-neck squamous cell carcinoma. Methods and Materials: Between 2004 and 2007, a total of 90 patients with locoregionally advanced head-and-neck squamous cell carcinoma underwent irradiation according to a hybrid fractionation schedule consisting of 20 fractions of 2 Gy (once daily) followed by 20 fractions of 1.6 Gy (twice daily) to a total dose of 72 Gy. Concomitant Cx (cisplatinum 100 mg/m{sup 2}) was administered at the start of Weeks 1 and 4. Treatment outcome and toxicity were retrospectively compared with a previous patient group (n = 73) treated with the same schedule, but without concomitant Cx, between 2001 and 2004. Results: The locoregional control (LRC) rate was 70% after 2 years. Two-year overall and 2-year disease-free survival rates were 74% and 60%, respectively. In comparison with the RT-only group, an improvement of 15% in both LRC (p = 0.03) and overall survival (p = 0.09) was observed. All patients were treated to full radiation dose according to protocol, although the Cx schedule had to be adjusted in 12 patients. No acute Grade 4 or 5 toxicity was seen, but incidences of Grade 3 acute mucositis (74.5% vs. 50.7%; p = 0.002) and dysphagia (82.2% vs. 47.9%; p < 0.001) were significantly higher in the chemoradiotherapy group compared with patients treated with RT alone. Conclusion: With this chemoradiotherapy regimen, excellent LRC and survival rates were achieved, with acceptable acute toxicity.

  7. In vivo Raman spectroscopy of cervix cancers

    NASA Astrophysics Data System (ADS)

    Rubina, S.; Sathe, Priyanka; Dora, Tapas Kumar; Chopra, Supriya; Maheshwari, Amita; Krishna, C. Murali

    2014-03-01

    Cervix-cancer is the third most common female cancer worldwide. It is the leading cancer among Indian females with more than million new diagnosed cases and 50% mortality, annually. The high mortality rates can be attributed to late diagnosis. Efficacy of Raman spectroscopy in classification of normal and pathological conditions in cervix cancers on diverse populations has already been demonstrated. Our earlier ex vivo studies have shown the feasibility of classifying normal and cancer cervix tissues as well as responders/non-responders to Concurrent chemoradiotherapy (CCRT). The present study was carried out to explore feasibility of in vivo Raman spectroscopic methods in classifying normal and cancerous conditions in Indian population. A total of 182 normal and 132 tumor in vivo Raman spectra, from 63 subjects, were recorded using a fiberoptic probe coupled HE-785 spectrometer, under clinical supervision. Spectra were acquired for 5 s and averaged over 3 times at 80 mW laser power. Spectra of normal conditions suggest strong collagenous features and abundance of non-collagenous proteins and DNA in case of tumors. Preprocessed spectra were subjected to Principal Component-Linear Discrimination Analysis (PCLDA) followed by leave-one-out-cross-validation. Classification efficiency of ~96.7% and 100% for normal and cancerous conditions respectively, were observed. Findings of the study corroborates earlier studies and suggest applicability of Raman spectroscopic methods in combination with appropriate multivariate tool for objective, noninvasive and rapid diagnosis of cervical cancers in Indian population. In view of encouraging results, extensive validation studies will be undertaken to confirm the findings.

  8. Brachytherapy boost in loco-regionally advanced nasopharyngeal carcinoma: a prospective randomized trial of the International Atomic Energy Agency

    PubMed Central

    2014-01-01

    Abstact Background The purpose was to determine whether a brachytherapy boost improves outcomes in patients with advanced nasopharyngeal carcinoma treated with standard chemo-radiotherapy. Methods Patients with nasopharyngeal carcinoma WHO grades I-III and TNM stages III or non-metastatic stage IV were eligible for this phase III study. Patients were randomized to either arm (A) induction chemotherapy, followed by external beam radiotherapy (EBRT) with concomitant cisplatin (n = 139) or arm (B), the same schedule plus a brachytherapy boost to the nasopharynx (n = 135). The EBRT doses given were 70 Gy to the primary tumour and positive lymph nodes and 46 Gy to the negative neck. The additional brachytherapy boost in arm (B) was given by either low dose-rate (LDR – 11 Gy) or high dose-rate (HDR – 3 fractions of 3.0 Gy) brachytherapy. The primary endpoint was 3-year overall survival (OS) and secondary endpoints were: local control, regional control, distant metastasis and grade 3–4 adverse events. Results 274 patients were randomized between September 2004 and December 2008. The two arms were comparable with regard to age, gender, stage and grade. 273 patients completed treatment. Median follow-up was 29 months (0.2-67 months). The effect of treatment arm, country, age, gender, WHO pathology, stage (T3-4, N2-3 versus other) and chemotherapy on overall survival (OS), disease-free survival (DFS) and local recurrence-free survival (LRFS) was studied. Stage significantly affected OS (p = 0.024) and DFS (p = 0.018) while age significantly affected OS (p = 0.014). None of the other factors studied were significant. The 3-year LRFS was 60.5% and 54.4% in arms A and B respectively (p = 0.647). The 3-year regional control rate in the neck was 59.7% and 54.3% respectively (p = 0.7). Distant metastasis developed in 59.7% of patients in arm A and 55.4% in arm B (p = 0.377). Patients with T1/T2 N + had a 3 year LRFS of 51.8% in Arm A (62 patients) versus 57.9% in Arm B (67

  9. The Irrigation Smear—A New Cytodiagnostic Technique for the Detection of Cancer of the Uterine Cervix

    PubMed Central

    Anderson, George H.; Krakauer, Kurt

    1967-01-01

    Using the Davis cytopipette, cytologic smears were prepared from 2014 patients; 1367 of these specimens were obtained by the patients themselves. The series included 57 cases of carcinoma or atypia of the cervix, and 50 (88%) of these cases were found to have abnormal cells in the irrigation smear. Cytopipette samples were obtained by a nurse from 647 Eskimos, but cell preservation in this group was not satisfactory because of a delay of several weeks in preparing the smears. Accurate results depend also on specific training of the personnel reading the smears because fewer cells may be present in these smears than in cervical scrape smears. The irrigation smear is recommended as a reasonably accurate method of screening women for cancer of the cervix if they are not being examined regularly by the cervical scrape method. Hospital admissions of females may be a fruitful source of such cases. PMID:6018053

  10. Reliability of recording uterine cancer in death certification in France and age-specific proportions of deaths from cervix and corpus uteri.

    PubMed

    Rogel, Agnès; Belot, Aurélien; Suzan, Florence; Bossard, Nadine; Boussac, Marjorie; Arveux, Patrick; Buémi, Antoine; Colonna, Marc; Danzon, Arlette; Ganry, Olivier; Guizard, Anne-Valérie; Grosclaude, Pascale; Velten, Michel; Jougla, Eric; Iwaz, Jean; Estève, Jacques; Chérié-Challine, Laurence; Remontet, Laurent

    2011-06-01

    French uterine cancer recordings in death certificates include 60% of "uterine cancer, Not Otherwise Specified (NOS)"; this hampers the estimation of mortalities from cervix and corpus uteri cancers. The aims of this work were to study the reliability of uterine cancer recordings in death certificates using a case matching with cancer registries and estimate age-specific proportions of deaths from cervix and corpus uteri cancers among all uterine cancer deaths by a statistical approach that uses incidence and survival data. Deaths from uterine cancer between 1989 and 2001 were extracted from the French National database of causes of death and case-to-case matched to women diagnosed with uterine cancer between 1989 and 1997 in 8 cancer registries. Registry data were considered as "gold-standard". Among the 1825 matched deaths, cancer registries recorded 830 cervix and 995 corpus uteri cancers. In death certificates, 5% and 40% of "true" cervix cancers were respectively coded "corpus" and "uterus, NOS" and 5% and 59% of "true" corpus cancers respectively coded "cervix" and "uterus, NOS". Miscoding cervix cancers was more frequent at advanced ages at death and in deaths at home or in small urban areas. Miscoding corpus cancers was more frequent in deaths at home or in small urban areas. From the statistical method, the estimated proportion of deaths from cervix cancer among all uterine cancer deaths was higher than 95% in women aged 30-40 years old but declined to 35% in women older than 70 years. The study clarifies the reason for poor encoding of uterus cancer mortality and refines the estimation of mortalities from cervix and corpus uteri cancers allowing future studies on the efficacy of cervical cancer screening.

  11. Radioembolization using 90Y-resin microspheres for patients with advanced hepatocellular carcinoma

    SciTech Connect

    Sangro, Bruno . E-mail: bsangro@unav.es; Bilbao, Jose I.; Boan, Jose; Martinez-Cuesta, Antonio; Benito, Alberto; Rodriguez, Javier; Panizo, Angel; Gil, Belen; Inarrairaegui, Mercedes; Herrero, Ignacio; Quiroga, Jorge; Prieto, Jesus

    2006-11-01

    Purpose: To investigate the antitumor effect of resin microspheres loaded with 90-yttrium against hepatocellular carcinoma and their safety in the setting of liver cirrhosis. Patients and Methods: Data from 24 consecutive patients with hepatocellular carcinoma (HCC) treated by radioembolization in the period from September 2003 to February 2005 were reviewed. Patients received no further antineoplastic therapy. A comprehensive evaluation was performed to prevent the risk of damage due to microsphere misplacing. Patients were discharged the day after microspheres injection. Results: Serious liver toxicity observed among cirrhotic patients in a first period was subsequently prevented by modifying the selection criteria and the method for calculating the activity to be administered. Among 21 patients evaluable for response using Response Evaluation Criteria in Solid Tumors (RECIST) criteria, a reduction in size of target lesions was observed in all but 1 patient. When considering only target lesions, disease control rate and response rate were 100% and 23.8%, respectively. However, 43% of patients progressed in the liver in the form of new lesions appearing a median time of 3 months after radioembolization. Conclusion: Our experience in these series of patients indicates that radioembolization using resin microspheres has a significant antitumor effect against HCC and that using stringent selection criteria and conservative models for calculating Radiation activity to be administered, radioembolization can be performed safely even in cirrhotic patients.

  12. Sorafenib plus hepatic arterial infusion chemotherapy with cisplatin versus sorafenib for advanced hepatocellular carcinoma: randomized phase II trial

    PubMed Central

    Ikeda, M.; Shimizu, S.; Sato, T.; Morimoto, M.; Kojima, Y.; Inaba, Y.; Hagihara, A.; Kudo, M.; Nakamori, S.; Kaneko, S.; Sugimoto, R.; Tahara, T.; Ohmura, T.; Yasui, K.; Sato, K.; Ishii, H.; Furuse, J.; Okusaka, T.

    2016-01-01

    Background Sorafenib (Sor) is acknowledged as a standard therapy for advanced hepatocellular carcinoma (HCC). This trial was conducted to evaluate the effect of addition of hepatic arterial infusion chemotherapy with cisplatin (SorCDDP) to Sor for the treatment of advanced HCC. Patients and methods We conducted a multicenter open-labeled randomized phase II trial in chemo-naïve patients with advanced HCC with Child-Pugh scores of 5–7. Eligible patients were randomly assigned 2:1 to receive SorCDDP (sorafenib: 400 mg bid; cisplatin: 65 mg/m2, day 1, every 4–6 weeks) or Sor (400 mg bid). The primary end point was overall survival. Results A total of 108 patients were randomized (Sor, n = 42; SorCDDP, n = 66). The median survival in the Sor and SorCDDP arms were 8.7 and 10.6 months, respectively [stratified hazard ratio (95% confidence interval), 0.60 (0.38–0.96), P = 0.031]. The median time to progression and the response rate were, respectively, 2.8 months and 7.3% in the Sor arm and 3.1 months and 21.7% in the SorCDDP arm. The adverse events were more frequent in the SorCDDP arm than in the Sor arm, but well-tolerated. Conclusion SorCDDP yielded favorable overall survival when compared with Sor in patients with advanced HCC. Clinical Trial registration UMIN-CTR (http://www.umin.ac.jp/ctr/index-j.htm), identification number: UMIN000005703. PMID:27573564

  13. Rhabdomyosarcoma of Cervix: A Case Report

    PubMed Central

    Hosseini, Maryam Sadat; Ashrafganjoei, Tahereh; Sourati, Ainaz; Tabatabeifar, Morteza; Mohamadianamiri, Mahdiss

    2016-01-01

    Introduction Rhabdomyosarcoma has known as a highly malignant soft tissue sarcoma. It has been the most common soft tissue sarcoma in childhood, accounting for about 3 to 4 % of all cases of childhood cancer. Rhabdomyosarcoma was rare in adults, accounting for 3% of all soft-tissue sarcomas. embryonal rhabdomyosarcoma of female genital tract including uterine cervix in an adult was rare. Case Presentation This study has reported a 33-year-old woman presented with abnormal vaginal discharge. Gynecologic examination revealed a cervical mass with grape- like feature protruding into vagina with posterior- superior vaginal wall involvement. Biopsy has performed and pathologic examination was consistent with embryonal botryoid type rhabdomyosarcoma. She has undergone the staging work up measurements including thoracic computed tomography (CT) scan, abdominopelvic magnetic resonance imaging (MRI), bone scan and bone marrow examination. In exception of abdominopelvic MRI, with 2 suspicious pelvic lymph nodes in addition of cervical mass, all others were normal. Radical hysterectomy with lymph node debulking and ovarian preservation has performed. Final results have shown embryonal botryoid type rhabdomyosarcoma of cervix. ovaries, endometrium, parametrium, and follopian tubes were unremarkable. Pelvic lymph nodes pathology and intraabdominal fluid cytology were negative for malignancy. Lymphovascular invasion was identified. She has advised for adjuvant chemotherapy. Conclusions This case has reminded that embryonal rhabdomyosarcoma could occur in uncommon site and older female. Longer follow up of these cases has required due to lack of survival data for embryonal rhabdomyosarcoma of this site and age group. PMID:27703644

  14. Automatic evaluation of uterine cervix segmentations

    NASA Astrophysics Data System (ADS)

    Lotenberg, Shelly; Gordon, Shiri; Long, Rodney; Antani, Sameer; Jeronimo, Jose; Greenspan, Hayit

    2007-03-01

    In this work we focus on the generation of reliable ground truth data for a large medical repository of digital cervicographic images (cervigrams) collected by the National Cancer Institute (NCI). This work is part of an ongoing effort conducted by NCI together with the National Library of Medicine (NLM) at the National Institutes of Health (NIH) to develop a web-based database of the digitized cervix images in order to study the evolution of lesions related to cervical cancer. As part of this effort, NCI has gathered twenty experts to manually segment a set of 933 cervigrams into regions of medical and anatomical interest. This process yields a set of images with multi-expert segmentations. The objectives of the current work are: 1) generate multi-expert ground truth and assess the diffculty of segmenting an image, 2) analyze observer variability in the multi-expert data, and 3) utilize the multi-expert ground truth to evaluate automatic segmentation algorithms. The work is based on STAPLE (Simultaneous Truth and Performance Level Estimation), which is a well known method to generate ground truth segmentation maps from multiple experts' observations. We have analyzed both intra- and inter-expert variability within the segmentation data. We propose novel measures of "segmentation complexity" by which we can automatically identify cervigrams that were found difficult to segment by the experts, based on their inter-observer variability. Finally, the results are used to assess our own automated algorithm for cervix boundary detection.

  15. Planned preoperative radiation therapy vs. definitive radiotherapy for advanced laryngeal carcinoma

    SciTech Connect

    Kazem, I.; van den Broek, P.

    1984-10-01

    In the period 1970-1980 inclusive, 191 patients with T3T4 laryngeal carcinoma (glottic: 63 and supraglottic: 128) received either definitive radiation therapy (RT) (60-65 Gy in 6-7 weeks) or planned preoperative radiation therapy (25 Gy in 5 equal daily fractions of 5 Gy) followed by laryngectomy with or without neck dissection (RT + S). Selection for RT vs. RT + S was based on medical operability and/or patient's refusal to undergo surgery. All patients are evaluable with minimum of 2 years observation. Crude 5 and 10-year survival probability for 32 patients with glottic localization who received RT is 55% and 38% vs. 65% and 65% respectively for 31 treated with RT + S. For 52 patients with supraglottic site who received RT, the 5 and 10-year survival is 44% and 44% vs. 82% and 60% for 76 patients treated with RT + S.

  16. Role of regorafenib as second-line therapy and landscape of investigational treatment options in advanced hepatocellular carcinoma

    PubMed Central

    Trojan, Jörg; Waidmann, Oliver

    2016-01-01

    Sorafenib is still the only systemic drug approved for the treatment of advanced hepatocellular carcinoma (HCC). In recent years, several investigational agents mainly targeting angiogenesis failed in late-phase clinical development due to either toxicity or lack of benefit. Recently, data of the RESORCE trial, a placebo-controlled Phase III study that evaluated the efficacy and safety of regorafenib in patients with HCC and documented disease progression after systemic first-line treatment with sorafenib, were presented at the ESMO World Congress on Gastrointestinal Cancer, 2016. Regorafenib treatment resulted in a 2.8-month survival benefit compared to placebo (10.6 months vs 7.8 months). Side effects were consistent with the known profile of regorafenib. The approval of regorafenib for this indication is expected in 2017. Further candidate agents in Phase III evaluation for second-line treatment of patients with HCC are the MET inhibitors tivantinib and cabozantinib, the vascular endothelial growth factor receptor-2 antibody ramucirumab, and the programmed death receptor-1 (PD-1) blocking antibody pembrolizumab. Furthermore, results from two first-line trials with either the tyrosine kinase inhibitor lenvatinib or the PD-1 antibody nivolumabin in comparison to sorafenib are awaited in the near future and might further change the treatment sequence of advanced HCC. PMID:27703962

  17. Risk factors for sorafenib-induced high-grade skin rash in Japanese patients with advanced renal cell carcinoma.

    PubMed

    Tsuchiya, Norihiko; Narita, Shintaro; Inoue, Takamitsu; Hasunuma, Naoko; Numakura, Kazuyuki; Horikawa, Yohei; Satoh, Shigeru; Notoya, Takeshi; Fujishima, Naohito; Hatakeyama, Shingo; Ohyama, Chikara; Habuchi, Tomonori

    2013-03-01

    The aim of this study was to evaluate the clinical factors, drug-related genetic polymorphisms, and human leukocyte antigen (HLA) types to determine the association with sorafenib-induced high-grade skin rash (HGSR) in Japanese patients with advanced renal cell carcinoma (RCC). A total of 55 patients with advanced RCC treated with sorafenib were analyzed retrospectively. Of these, 33 patients were subjected to HLA typing and polymorphism analyses of CYP3A5, ABCB1, ABCC2, and UGT1A1, which are involved in the metabolism and membrane transport of sorafenib. Grade 3 or higher SR developed in 12 (22%), and a higher incidence was observed in female patients than in male patients (40 vs. 15%, P=0.046). The initial dose, initial dose per body weight, and initial dose per body surface area in patients with HGSR were significantly higher than those in patients without HGSR. Patients with the ABCC2 -24CC genotype were at a significantly higher risk of SR than those with the CT genotype (35 vs. 0%, P=0.032). HLA-A*24 was significantly associated with the occurrence of HGSR (P=0.049). Our finding suggested that women, higher initial dose per body weight or body surface area, the ABCC2 -24CC genotype, and HLA-A*24 are associated with the risk of sorafenib-induced HGSR in Japanese RCC patients.

  18. MRI-detectable polymeric micelles incorporating platinum anticancer drugs enhance survival in an advanced hepatocellular carcinoma model

    PubMed Central

    Vinh, Nguyen Quoc; Naka, Shigeyuki; Cabral, Horacio; Murayama, Hiroyuki; Kaida, Sachiko; Kataoka, Kazunori; Morikawa, Shigehiro; Tani, Tohru

    2015-01-01

    Hepatocellular carcinoma (HCC) is one of the most intractable and lethal cancers; most cases are diagnosed at advanced stages with underlying liver dysfunction and are frequently resistant to conventional chemotherapy and radiotherapy. The development of tumor-targeting systems may improve treatment outcomes. Nanomedicine platforms are of particular interest for enhancing chemotherapeutic efficiency, and they include polymeric micelles, which enable targeting of multiple drugs to solid tumors, including imaging and therapeutic agents. This allows concurrent diagnosis, targeting strategy validation, and efficacy assessment. We used polymeric micelles containing the T1-weighted magnetic resonance imaging contrast agent gadolinium-diethylenetriaminpentaacetic acid (Gd-DTPA) and the parent complex of the anticancer drug oxaliplatin [(1,2-diaminocyclohexane)platinum(II) (DACHPt)] for simultaneous imaging and therapy in an orthotopic rat model of HCC. The Gd-DTPA/DACHPt-loaded micelles were injected into the hepatic artery, and magnetic resonance imaging performance and antitumor activity against HCC, as well as adverse drug reactions were assessed. After a single administration, the micelles achieved strong and specific tumor contrast enhancement, induced high levels of tumor apoptosis, and significantly suppressed tumor size and growth. Moreover, the micelles did not induce severe adverse reactions and significantly improved survival outcomes in comparison to oxaliplatin or saline controls. Our results suggest that Gd-DTPA/DACHPt-loaded micelles are a promising approach for effective diagnosis and treatment of advanced HCC. PMID:26203241

  19. Anatomic and Dosimetric Changes During the Treatment Course of Intensity-Modulated Radiotherapy for Locally Advanced Nasopharyngeal Carcinoma

    SciTech Connect

    Wang Xin; Lu Jiade; Xiong Xiaopeng; Zhu Guopei; Ying Hongmei; He Shaoqin; Hu Weigang; Hu Chaosu

    2010-07-01

    Many patients with nasopharyngeal carcinoma (NPC) have marked anatomic change during intensity-modulated radiation therapy (IMRT). In this study, the magnitude of anatomic changes and its dosimetric effects were quantified. Fifteen patients with locally advanced NPC treated with IMRT had repeated computed tomography (CT) after 18 fractions. A hybrid plan was made to the anatomy of the second computed tomography scan. The dose of the original plan, hybrid plan, and new plan were compared. The mean volume of left and right parotid decreased 6.19 mL and 6.44 mL, respectively. The transverse diameters of the upper bound of odontoid process, the center of odontoid process, and the center of C2 vertebral body slices contracted with the mean contraction of 8.2 mm, 9.4 mm, and 7.6 mm. Comparing the hybrid plan with the treatment plan, the coverage of target was maintained while the maximum dose to the brain stem and spinal cord increased by 0.08 to 6.51 Gy and 0.05 to 7.8 Gy. The mean dose to left and right parotid increased by 2.97 Gy and 2.57 Gy, respectively. A new plan reduced the dose of spinal cord, brain stem, and parotids. Measurable anatomic changes occurring during the IMRT for locally advanced NPC maintained the coverage of targets but increased the dose to critical organs. Those patients might benefit from replanning.

  20. Comparison of Acute Toxicities in Two Primary Chemoradiation Regimens in the Treatment of Advanced Head and Neck Squamous Cell Carcinoma

    PubMed Central

    Fan, Katherine Y.; Gogineni, Hrishikesh; Zaboli, David; Lake, Spencer; Zahurak, Marianna L.; Best, Simon R.; Levine, Marshall A.; Tang, Mei; Zinreich, Eva S.; Saunders, John R.; Califano, Joseph A.; Blanco, Ray G.; Pai, Sara I.; Messing, Barbara; Ha, Patrick K.

    2013-01-01

    Purpose The optimal dosage and frequency of platinum-based chemoradiotherapy (CRT) regimen for treating advanced head and neck squamous cell carcinoma remains unresolved. This study aims to compare the toxicity and efficacy of weekly versus more dose-intensive cisplatin-based CRTs. Methods We reviewed 155 stage III/IV head and neck squamous cell carcinoma patients with no evidence of distant metastasis treated with one of two CRT regimens from 2000 to 2010 at Greater Baltimore Medical Center. Twice-daily radiation was provided as a split course over a 45-day period. Regimen A consisted of concomitant cisplatin (30 mg/m2/1 h) weekly for 6 cycles; regimen B consisted of concomitant cisplatin (12 mg/m2/1 h) and 5-fluorouracil (600 mg/m2/20 h) on days 1 through 5 and days 29 through 33. Main outcome measures included acute toxicities (myelosuppression, neurotoxicity, nephrotoxicity, gastrointestinal dysfunction), unplanned hospitalizations, and disease control at 12 months. Results Patients on regimen A were much less likely to experience ototoxicity due to their treatment (0% vs. 9.8%, P = 0.04). They were more likely to experience thrombocytopenia acutely (46% vs. 26%, P = 0.02), but the toxicity was not limiting (grade 1–2). No significant differences exist in the incidence of other toxicities or unplanned hospitalizations. At 1 year, 97% of patients on A vs. 86% of patients on regimen B were free of disease (P = 0.11). Conclusions With concurrent radiotherapy, low-dose, single-agent, weekly cisplatin is less likely than higher-dose daily cisplatin plus 5-fluorouracil provided at the beginning and end of treatment to be associated with ototoxicity. The preliminary data suggest at least equivalent efficacy, but longer follow-up is required. PMID:22290566

  1. Neoadjuvant chemotherapy in early-stage and locally advanced small bulk squamous cell carcinoma of the oral cavity and oropharynx.

    PubMed

    Tichler, T; Ramon, Y; Rath, P; Hendler, S; Brenner, H J

    1988-01-01

    Thirty patients with Stages I, II and III squamous cell carcinoma of the oral cavity and oropharynx (6, 12 and 12 patients, respectively) were entered into a combined modality protocol using preoperative chemotherapy, followed by resection with or without radical neck dissection and radiotherapy. None of the patients received prior treatment and all had good performance status. Primary sites included alveolar ridge (in nine patients), buccal mucosa (in eight), tongue (in six), floor of mouth (in five), and hard palate and tonsillar fossa in one each. Chemotherapy was given as a neoadjuvant debulking procedure using two courses of the Price-Hill regimen (5FU, methotrexate with citrovorum rescue, vincristine, bleomycin, and hydrocortisone) followed in 10 to 14 days by local resection for Stage I-II patients and radical neck dissection plus radiotherapy for Stage III patients. Response to chemotherapy alone was observed in 70% (21 of 30), with 17% (5 of 30) complete responders. Responses were seen in 100% of Stage I, 75% of Stage II, and 50% of Stage III patients. Age greater than 80 years was a poor prognostic indicator. Both men and women responded equally well. Of the 25 patients not entering CR with chemotherapy, a further 75% (11 of 15) did so after local resection and 50% (5 of 10) after local resection, radical neck dissection, and radiotherapy. Overall salvage rate post chemotherapy was 64% (16 of 25). All five patients in CR with chemotherapy alone are alive at a median follow-up time of greater than or equal to 43 months; full survival data are discussed. Toxicity was minimal and did not affect change in treatment course in any patient. These results show that further investigations on the use of neoadjuvant chemotherapy in early-stage and locally advanced squamous cell carcinoma of the oral cavity and oropharynx are indicated.

  2. Targeting BRAF aberrations in advanced colorectal carcinoma: from bench to bedside.

    PubMed

    Abdel-Rahman, Omar

    2016-01-01

    Colorectal cancer (CRC) is a global health problem with profound mortality and morbidity effects particularly in the advanced/metastatic setting. Because of the recent understanding of the biology of this disease, many candidate targets have come into light for therapeutic evaluation. The current review is about evaluating the preclinical and clinical aspects of BRAF as a therapeutic target in this disease. The available clinical results suggest that while the use of unselective RAF inhibitors (e.g., sorafenib) has been ineffective in the management of advanced CRC patients with KRAS mutation, combination of selective BRAF inhibitors plus EGFR inhibitors may represent a good therapeutic strategy in BRAF-mutant CRC. PMID:26616508

  3. Living Donor Liver Transplantation for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis after Concurrent Chemoradiation Therapy

    PubMed Central

    Han, Dai Hoon; Joo, Dong Jin; Kim, Myoung Soo; Choi, Gi Hong; Choi, Jin Sub; Park, Young Nyun; Seong, Jinsil

    2016-01-01

    Locally advanced hepatocellular carcinoma (HCC) with portal vein thrombosis carries a 1-year survival rate <10%. Localized concurrent chemoradiotherapy (CCRT), followed by hepatic arterial infusion chemotherapy (HAIC), was recently introduced in this setting. Here, we report our early experience with living donor liver transplantation (LDLT) in such patients after successful down-staging of HCC through CCRT and HAIC. Between December 2011 and September 2012, eight patients with locally advanced HCC at initial diagnosis were given CCRT, followed by HAIC, and underwent LDLT at the Severance Hospital, Seoul, Korea. CCRT [45 Gy over 5 weeks with 5-fluorouracil (5-FU) as HAIC] was followed by HAIC (5-FU/cisplatin combination every 4 weeks for 3–12 months), adjusted for tumor response. Down-staging succeeded in all eight patients, leaving no viable tumor thrombi in major vessels, although three patients first underwent hepatic resections. Due to deteriorating liver function, transplantation was the sole therapeutic option and offered a chance for cure. The 1-year disease-free survival rate was 87.5%. There were three instances of post-transplantation tumor recurrence during follow-up monitoring (median, 17 months; range, 10–22 months), but no deaths occurred. Median survival time from initial diagnosis was 33 months. Four postoperative complications recorded in three patients (anastomotic strictures: portal vein, 2; bile duct, 2) were resolved through radiologic interventions. Using an intensive tumor down-staging protocol of CCRT followed by HAIC, LDLT may be a therapeutic option for selected patients with locally advanced HCC and portal vein tumor thrombosis. PMID:27401662

  4. Phase II trial of bevacizumab and erlotinib as a second-line therapy for advanced hepatocellular carcinoma

    PubMed Central

    Kaseb, Ahmed O; Morris, Jeffrey S; Iwasaki, Michiko; Al-Shamsi, Humaid O; Raghav, Kanwal Pratap Singh; Girard, Lauren; Cheung, Sheree; Nguyen, Van; Elsayes, Khaled M; Xiao, Lianchun; Abdel-Wahab, Reham; Shalaby, Ahmed S; Hassan, Manal; Hassabo, Hesham M; Wolff, Robert A; Yao, James C

    2016-01-01

    Trial registry Clinicaltrials.gov #NCT01180959. Background Early clinical studies of bevacizumab and erlotinib in advanced hepatocellular carcinoma (HCC) have a tolerable toxicity and a promising clinical outcome. We evaluated the efficacy and tolerability of this combination as a second-line therapy for HCC refractory to sorafenib. Methods For this single-arm, Phase II study, we recruited patients with Child–Pugh class A or B liver disease, Eastern Cooperative Oncology Group performance status 0–2, and advanced HCC that was not amenable to surgical or regional therapies and treatment with sorafenib had failed (disease progressed or patient could not tolerate sorafenib). Patients received 10 mg/kg intravenous bevacizumab every 14 days and 150 mg oral erlotinib daily for 28-day cycles until progression. Tumor response was evaluated every two cycles using Response Evaluation Criteria in Solid Tumors. The primary end point was the 16-week progression-free survival rate. Secondary end points included time to progression and overall survival. Results A total of 44 patients were enrolled and had a median follow-up time of 33.8 months (95% confidence interval [CI]: 23.5 months – not defined). The 16-week progression-free survival rate was 43% (95% CI: 28%–59%), median time to progression was 3.9 months (95% CI: 2.0–8.3 months), and median overall survival duration was 9.9 months (95% CI: 8.3–15.5 months). Grade 3–4 adverse events included fatigue (13%), acne (11%), diarrhea (9%), anemia (7%), and upper gastrointestinal hemorrhage (7%). Conclusion Bevacizumab plus erlotinib was tolerable and showed a signal of survival benefit in the second-line setting for patients with advanced HCC. Because standard-of-care options are lacking in this setting, further studies to identify predictors of response to this regimen are warranted. PMID:26929648

  5. Living Donor Liver Transplantation for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis after Concurrent Chemoradiation Therapy.

    PubMed

    Han, Dai Hoon; Joo, Dong Jin; Kim, Myoung Soo; Choi, Gi Hong; Choi, Jin Sub; Park, Young Nyun; Seong, Jinsil; Han, Kwang Hyub; Kim, Soon Il

    2016-09-01

    Locally advanced hepatocellular carcinoma (HCC) with portal vein thrombosis carries a 1-year survival rate <10%. Localized concurrent chemoradiotherapy (CCRT), followed by hepatic arterial infusion chemotherapy (HAIC), was recently introduced in this setting. Here, we report our early experience with living donor liver transplantation (LDLT) in such patients after successful down-staging of HCC through CCRT and HAIC. Between December 2011 and September 2012, eight patients with locally advanced HCC at initial diagnosis were given CCRT, followed by HAIC, and underwent LDLT at the Severance Hospital, Seoul, Korea. CCRT [45 Gy over 5 weeks with 5-fluorouracil (5-FU) as HAIC] was followed by HAIC (5-FU/cisplatin combination every 4 weeks for 3-12 months), adjusted for tumor response. Down-staging succeeded in all eight patients, leaving no viable tumor thrombi in major vessels, although three patients first underwent hepatic resections. Due to deteriorating liver function, transplantation was the sole therapeutic option and offered a chance for cure. The 1-year disease-free survival rate was 87.5%. There were three instances of post-transplantation tumor recurrence during follow-up monitoring (median, 17 months; range, 10-22 months), but no deaths occurred. Median survival time from initial diagnosis was 33 months. Four postoperative complications recorded in three patients (anastomotic strictures: portal vein, 2; bile duct, 2) were resolved through radiologic interventions. Using an intensive tumor down-staging protocol of CCRT followed by HAIC, LDLT may be a therapeutic option for selected patients with locally advanced HCC and portal vein tumor thrombosis. PMID:27401662

  6. Precancerous lesions of the cervix uteri in infertile women.

    PubMed

    Holst, N; Abyholm, T

    1983-10-01

    A study of 318 patients with tubal infertility and a control group of 200 unselected infertile women yielded 14 (4.4%) and 1 (0.5%), respectively, with precancerous lesions of the cervix uteri. The one patient in the control group with severe dysplasia was later shown to have tubal infertility. The overall incidence of premalignant lesions of the cervix uteri as reported to the National Cancer Registry of Norway was 0.1% for the age group and period studied. Women with tubal infertility represent a small but comparatively high risk group for the development of precancerous lesions of the cervix uteri.

  7. Frequency of Elevated Hepatocellular Carcinoma (HCC) Biomarkers in Patients with Advanced Hepatitis C

    PubMed Central

    Sterling, Richard K.; Wright, Elizabeth C.; Morgan, Timothy R.; Seeff, Leonard B.; Hoefs, John C.; Di Bisceglie, Adrian M.; Dienstag, Jules L.; Lok, Anna S.

    2013-01-01

    Background Prospective studies of serum HCC biomarkers in patients with advanced hepatitis C are lacking. Aims To determine frequencies and performance of elevated alpha-fetoprotein (AFP), AFP-L3, and des-gamma-carboxy prothrombin (DCP) levels as HCC biomarkers in advanced hepatitis C. Methods Patients in the HALT-C Trial were tested every 3 months for 42 months. Screening ultrasound was performed every 12 months. Levels of biomarkers were compared in patients in whom HCC did or did not develop. Results 855 patients were evaluated; HCC developed in 46. Among patients without HCC, 73.2% had AFP consistently <20, 24.5% had at least one AFP between 20-199, while 2.3% had at least one AFP value ≥200 ng/mL; 73.7% had DCP consistently <90, 11.6% had at least one DCP between 90-149, and 14.7% had at least one DCP value ≥150 mAU/mL. AFP-L3 ≥10% was present at least once in 9.0% and in 17.1% of those with AFP >20 ng/mL. Among all patients with elevated biomarkers, a diagnosis of HCC was made in 0-31.6% (depending on the biomarker and cutoff) during the subsequent 24 months. AFP ≥200 ng/mL had the highest specificity (99%), but sensitivity was ≤20%. DCP ≥40 mAU/mL had the highest sensitivity (76%), but specificity was ≤58%. Independent predictors of elevated AFP were gender (female), race (Black), more advanced disease, and HCC. Elevated DCP was associated with more advanced disease and HCC. Conclusions Mild-moderate elevations in total AFP and DCP but not AFP-L3 occur frequently in patients with chronic hepatitis C and advanced fibrosis, are related to factors other than HCC, and are poor predictors of HCC. PMID:21931376

  8. High Dickkopf-1 expression is associated with poor prognosis in patients with advanced urothelial carcinoma

    PubMed Central

    SHEN, CHENG-HUANG; HSIEH, HSIAO-YEN; WANG, YUAN-HUNG; CHEN, SYUE-YI; TUNG, CHUN-LIANG; WU, JIANN-DER; LIN, CHANG-TE; CHAN, MICHAEL W.-Y.; HSU, CHENG-DA; CHANG, DECHING

    2010-01-01

    Although Dickkopf-1 (DKK1) has been demonstrated to be associated with tumorigenesis in various types of human tumors, a correlation between DKK1 and urothelial carcinoma (UC) has not been reported. In the present study, the correlation between DKK1 expression and UC progression was investigated. Seventy-five UC patients were enrolled. The expression of DKK1 in serum and UC tissue was detected by ELISA, real-time PCR and Western blotting. Prognostic significance was assessed by using Kaplan-Meier survival estimates and log-rank tests. The results showed that serum levels of DKK1 were significantly higher in the UC patients with muscle-invasive (p=0.0001) and high-grade tumors (p=0.00001) as compared to the controls. A high-serum DKK1 was also associated with poor disease-free survival in the UC patients (hazard ratio=2.44; 95% CI 1.10–5.40; p=0.028). Furthermore, DKK1 was also overexpressed in 93% (41/44) of the UC tissues. Therefore, the findings indicate that the expression of DKK1 is associated with UC progression. PMID:22993615

  9. Advances in computed tomography and magnetic resonance imaging of hepatocellular carcinoma

    PubMed Central

    Hennedige, Tiffany; Venkatesh, Sudhakar K

    2016-01-01

    Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Imaging is important for establishing a diagnosis of HCC and early diagnosis is imperative as several potentially curative treatments are available when HCC is small. Hepatocarcinogenesis occurs in a stepwise manner on a background of chronic liver disease or cirrhosis wherein multiple genes are altered resulting in a range of cirrhosis-associated nodules. This progression is related to increased cellularity, neovascularity and size of the nodule. An understanding of the stepwise progression may aid in early diagnosis. Dynamic and multiphase contrast-enhanced computed tomography and magnetic resonance imaging still form the cornerstone in the diagnosis of HCC. An overview of the current diagnostic standards of HCC in accordance to the more common practicing guidelines and their differences will be reviewed. Ancillary features contribute to diagnostic confidence and has been incorporated into the more recent Liver Imaging Reporting and Data System. The use of hepatocyte-specific contrast agents is increasing and gradually changing the standard of diagnosis of HCC; the most significant benefit being the lack of uptake in the hepatocyte phase in the earlier stages of HCC progression. An outline of supplementary techniques in the imaging of HCC will also be reviewed. PMID:26755871

  10. Continuous infusion of 5-fluorouracil with alpha 2b interferon for advanced colorectal carcinoma.

    PubMed Central

    Ferguson, J. E.; Hulse, P.; Lorigan, P.; Jayson, G.; Scarffe, J. H.

    1995-01-01

    Thirty patients with symptomatic colorectal carcinoma were commenced on treatment with 5-fluorouracil (2.5 g week-1) administered by continuous intravenous infusion and alpha 2b interferon (3 x 10(6) U s.c. three times a week). Six out of 30 patients (20%) achieved a partial response. Three patients (10%) had stable disease and 21 patients (70%) progressed on treatment. Twenty patients (67%) completed ten or more weeks of treatment. In nine patients, treatment was withdrawn after 2-9 weeks because of disease progression or death. One patient's treatment was interrupted by emergency surgery. The median survival for all patients was 210 days (7 months). The principal side-effects were oral mucositis (12/30 patients), nausea (8/30 patients) and transient diarrhoea (4/30 patients), and initial constitutional symptoms due to alpha 2b interferon. The combination of low-dose continuous infusional 5-fluorouracil and low-dose alpha 2b interferon is well tolerated but has no obvious advantage over alternative infusional regimens using 5-fluorouracil as a single agent. PMID:7599051

  11. IMRT With Simultaneous Integrated Boost and Concurrent Chemotherapy for Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck

    SciTech Connect

    Montejo, Michael E.; Shrieve, Dennis C.; Bentz, Brandon G.; Hunt, Jason P.; Buchman, Luke O.; Agarwal, Neeraj; Hitchcock, Ying J.

    2011-12-01

    Purpose: To evaluate the efficacy and toxicity of accelerated radiotherapy with concurrent chemotherapy in advanced head-and-neck squamous cell carcinoma. Methods and Materials: Between April 2003 and May 2008, 43 consecutive patients with advanced head-and-neck squamous cell carcinoma received accelerated chemoradiation with concurrent cisplatin or cetuximab. The doses for intensity-modulated radiotherapy with simultaneous integrated boost were 67.5, 60.0, and 54 Gy in 30 daily fractions of 2.25, 2.0, and 1.8 Gy to the planning target volumes for gross disease, high-risk nodes, and low-risk nodes, respectively. Results: Of the patients, 90.7% completed chemoradiotherapy as prescribed. The median treatment duration was 43 days (range, 38-55 days). The complete response rate was 74.4%. With median follow-up of 36.7 months (range, 16.8-78.1 months) in living patients, the estimated 1-, 2-, and 5-year locoregional control, overall survival, and disease-free survival rates were 82%, 82%, and 82%; 73%, 65%, and 61%; and 73%, 73%, and 70%, respectively. One treatment-related death occurred from renal failure. Grade 3 mucositis and dermatitis occurred in 13 patients (30.2%) and 3 patients (6.9%), respectively. Grade 2 xerostomia occurred in 12 patients (27.9%). In patients with adequate follow-up, 82% were feeding tube free by 6 months after therapy; 13% remained feeding tube dependent at 1 year. Grade 3 soft-tissue fibrosis, esophageal stricture, osteoradionecrosis, and trismus occurred in 3 patients (6.9%), 5 patients (11.6%), 1 patient (2.3%), and 3 patients (6.9%), respectively. Conclusions: Our results show that intensity-modulated radiotherapy with simultaneous integrated boost with concurrent chemotherapy improved local and regional control. Acute and late toxicities were tolerable and acceptable. A prospective trial of this fractionation regimen is necessary for further assessment of its efficacy and toxicity compared with other approaches.

  12. Reducing the risk of xerostomia and mandibular osteoradionecrosis: the potential benefits of intensity modulated radiotherapy in advanced oral cavity carcinoma.

    PubMed

    Ahmed, Merina; Hansen, Vibeke N; Harrington, Kevin J; Nutting, Christopher M

    2009-01-01

    Radiation therapy for squamous cell carcinoma of the oral cavity may be curative, but carries a risk of permanent damage to bone, salivary glands, and other soft tissues. We studied the potential of intensity modulated radiotherapy (IMRT) to improve target volume coverage, and normal tissue sparing for advanced oral cavity carcinoma (OCC). Six patients with advanced OCC requiring bilateral irradiation to the oral cavity and neck were studied. Standard 3D conformal radiotherapy (3DCRT) and inverse-planned IMRT dose distributions were compared by using dose-volume histograms. Doses to organs at risk, including spinal cord, parotid glands, and mandible, were assessed as surrogates of radiation toxicity. PTV1 mean dose was 60.8 +/- 0.8 Gy for 3DCRT and 59.8 +/- 0.1 Gy for IMRT (p = 0.04). PTV1 dose range was 24.7 +/- 6 Gy for 3DCRT and 15.3 +/- 4 Gy for IMRT (p = 0.001). PTV2 mean dose was 54.5 +/- 0.8 Gy for 3DCRT and for IMRT was 54.2 +/- 0.2 Gy (p = 0.34). PTV2 dose range was improved by IMRT (7.8 +/- 3.2 Gy vs. 30.7 +/- 12.8 Gy, p = 0.006). Homogeneity index (HI) values for PTV2 were closer to unity using IMRT (p = 0.0003). Mean parotid doses were 25.6 +/- 2.7 Gy for IMRT and 42.0 +/- 8.8 Gy with 3DCRT (p = 0.002). The parotid V30 in all IMRT plans was <45%. The mandible V50, V55, and V60 were significantly lower for the IMRT plans. Maximum spinal cord and brain stem doses were similar for the 2 techniques. IMRT provided superior target volume dose homogeneity and sparing of organs at risk. The magnitude of reductions in dose to the salivary glands and mandible are likely to translate into reduced incidence of xerostomia and osteoradionecrosis for patients with OCC.

  13. Reducing the Risk of Xerostomia and Mandibular Osteoradionecrosis: The Potential Benefits of Intensity Modulated Radiotherapy in Advanced Oral Cavity Carcinoma

    SciTech Connect

    Ahmed, Merina; Hansen, Vibeke N.; Harrington, Kevin J.; Nutting, Christopher M.

    2009-10-01

    Radiation therapy for squamous cell carcinoma of the oral cavity may be curative, but carries a risk of permanent damage to bone, salivary glands, and other soft tissues. We studied the potential of intensity modulated radiotherapy (IMRT) to improve target volume coverage, and normal tissue sparing for advanced oral cavity carcinoma (OCC). Six patients with advanced OCC requiring bilateral irradiation to the oral cavity and neck were studied. Standard 3D conformal radiotherapy (3DCRT) and inverse-planned IMRT dose distributions were compared by using dose-volume histograms. Doses to organs at risk, including spinal cord, parotid glands, and mandible, were assessed as surrogates of radiation toxicity. PTV1 mean dose was 60.8 {+-} 0.8 Gy for 3DCRT and 59.8 {+-} 0.1 Gy for IMRT (p = 0.04). PTV1 dose range was 24.7 {+-} 6 Gy for 3DCRT and 15.3 {+-} 4 Gy for IMRT (p = 0.001). PTV2 mean dose was 54.5 {+-} 0.8 Gy for 3DCRT and for IMRT was 54.2 {+-} 0.2 Gy (p = 0.34). PTV2 dose range was improved by IMRT (7.8 {+-} 3.2 Gy vs. 30.7 {+-} 12.8 Gy, p = 0.006). Homogeneity index (HI) values for PTV2 were closer to unity using IMRT (p = 0.0003). Mean parotid doses were 25.6 {+-} 2.7 Gy for IMRT and 42.0 {+-} 8.8 Gy with 3DCRT (p = 0.002). The parotid V30 in all IMRT plans was <45%. The mandible V50, V55, and V60 were significantly lower for the IMRT plans. Maximum spinal cord and brain stem doses were similar for the 2 techniques. IMRT provided superior target volume dose homogeneity and sparing of organs at risk. The magnitude of reductions in dose to the salivary glands and mandible are likely to translate into reduced incidence of xerostomia and osteoradionecrosis for patients with OCC.

  14. Dystocia due to urinary bladder carcinoma in two water buffaloes (bubalus bubalis) - Clinical case report.

    PubMed

    Nanda, A S; Sharma, R D

    1985-09-01

    Two buffaloes with full-term pregnancy suffered from dystocia because the cervix did not dilate in spite of strong labour pains and other parturition signs shown by each animal. The urinary bladder, cervix, vagina and surrounding area were very firm. Dead, emphysemated fetuses were removed by caesarean in each case and anuria was also noticed. One buffalo died and the other was euthanised after surgery because it did not improve. The post-mortem examinations revealed transitional cell carcinoma of urinary bladder infiltrating the cervix, vagina and surrounding area in each case.

  15. Associations of ATM Polymorphisms With Survival in Advanced Esophageal Squamous Cell Carcinoma Patients Receiving Radiation Therapy

    SciTech Connect

    Du, Zhongli; Zhang, Wencheng; Zhou, Yuling; Yu, Dianke; Chen, Xiabin; Chang, Jiang; Qiao, Yan; Zhang, Meng; Huang, Ying; Wu, Chen; Xiao, Zefen; Tan, Wen; and others

    2015-09-01

    Purpose: To investigate whether single nucleotide polymorphisms (SNPs) in the ataxia telangiectasia mutated (ATM) gene are associated with survival in patients with esophageal squamous cell carcinoma (ESCC) receiving radiation therapy or chemoradiation therapy or surgery only. Methods and Materials: Four tagSNPs of ATM were genotyped in 412 individuals with clinical stage III or IV ESCC receiving radiation therapy or chemoradiation therapy, and in 388 individuals with stage I, II, or III ESCC treated with surgery only. Overall survival time of ESCC among different genotypes was estimated by Kaplan-Meier plot, and the significance was examined by log-rank test. The hazard ratios (HRs) and 95% confidence intervals (CIs) for death from ESCC among different genotypes were computed by a Cox proportional regression model. Results: We found 2 SNPs, rs664143 and rs664677, associated with survival time of ESCC patients receiving radiation therapy. Individuals with the rs664143A allele had poorer median survival time compared with the rs664143G allele (14.0 vs 20.0 months), with the HR for death being 1.45 (95% CI 1.12-1.89). Individuals with the rs664677C allele also had worse median survival time than those with the rs664677T allele (14.0 vs 23.5 months), with the HR of 1.57 (95% CI 1.18-2.08). Stratified analysis showed that these associations were present in both stage III and IV cancer and different radiation therapy techniques. Significant associations were also found between the SNPs and locosregional progression or progression-free survival. No association between these SNPs and survival time was detected in ESCC patients treated with surgery only. Conclusion: These results suggest that the ATM polymorphisms might serve as independent biomarkers for predicting prognosis in ESCC patients receiving radiation therapy.

  16. Primary follicular lymphoma of the cervix uteri: a review.

    PubMed

    Korcum, Aylin Fidan; Karadogan, Ihsan; Aksu, Gamze; Aralasmak, Ayse; Erdogan, Gulgun

    2007-09-01

    Primary non-Hodgkin's lymphoma of the cervix is a rare disease, of which a subgroup of follicular lymphoma constitutes only 8.5%. There is not an established treatment protocol neither for primary cervical lymphoma nor for its follicular subgroup. We presented a case with Ann Arbor stage IEA (Extra-nodal involvement and absence of weight loss, fever, night sweat) primary follicular lymphoma of the cervix. She was treated with chemotherapy followed by pelvic radiotherapy. Upon relapse with a nodal neck mass, she was treated with rituximab alone. She remained well for 23 months after rituximab. In the 39 months of follow-up, there was no evidence of disease. In the light of our case, we reviewed the reported cases of primary follicular lymphoma of the cervix while discussing their treatment protocols and the cases of primary cervix lymphoma treated with rituximab.

  17. Examination of the cervix with the naked eye using acetic acid test.

    PubMed

    Ottaviano, M; La Torre, P

    1982-05-15

    Examination of the cervix was carried out on 2,400 patients, by use of acetic acid test with the naked eye and the colposcope. The physiologic transformation zone was clearly identified both with the naked eye and the colposcope in 1,568 of 1,594 (99%) cases. Colposcopic examination was unsatisfactory in 108 of the 264 (41%) patients in whom the cervix was completely covered by normal squamous epithelium. An atypical transformation zone (ATZ) was identified with the naked eye as white epithelium in 98.4% and as "suspicious" in 1.6% of 312 colposcopically controlled cases. An unsatisfactory colposcopic examination occurred in 39 of the 312 (12.5%) patients with an ATZ. Final histologic diagnosis for 312 ATZs was benign lesion in 169 of 312 (54.2%), cervical intraepithelial neoplasia (CIN) grades 1 and 2 in 81 of 312 (26%), grade 3 CIN in 56 of 312 (17.9%), and preclinical invasive carcinoma in 6 of 312 (1.9%). The detection of intraepithelial or preclinical invasive cervical neoplasias should not depend on the possession of a colposcope. On the other hand, the use of a colposcope is essential for the selection of CIN that can be treated with ultraconservative therapy or with colposcopically directed conization.

  18. Association of educational levels with survival in Indian patients with cancer of the uterine cervix.

    PubMed

    Krishnatreya, Manigreeva; Kataki, Amal Chandra; Sharma, Jagannath Dev; Nandy, Pintu; Gogoi, Gayatri

    2015-01-01

    The main objective of this paper was to assess the influence of educational level on the survival of uterine cervix cancer patients in our population. A total of 224 patients were registered in our registry, of which 178 had information on stage and different educational levels. The overall median survival (MS) was 23 months, with values of 18.5, 20.7 and 41.3 months for the illiterate, literate and qualified groups, respectively. In the illiterate patients, stage I was seen in 2.6% and stage IV in 11.8%, while in other 2 groups stage I was seen in 10% to 17% of patients at the time of diagnosis. The survival probability at around 50 months was around 42%, 30% and 26% (approximately) for qualified, literates and illiterates respectively [Log Rank (Mantel-Cox) showed p=0.023]. Emphasis on imparting education to females can be a part of comprehensive cancer control programme for improving the overall survival in patients with carcinoma of the uterine cervix in our population.

  19. The long-term outcomes of alternating chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma: a multiinstitutional phase II study

    PubMed Central

    Fuwa, Nobukazu; Kodaira, Takeshi; Daimon, Takashi; Yoshizaki, Tomokazu

    2015-01-01

    To examine the long-term outcomes of alternating chemoradiotherapy (ALCRT) for patients with locoregionally advanced nasopharyngeal carcinoma (NPC) and to assess the efficacy of ALCRT for NPC. Patients with stage IIB to IVB, ECOG PS 0–2, 18–70 years-old, and sufficient organ function were eligible for this study. First, chemotherapy, consisting of 5-fluorouracil (800 mg/m2 per 24 h on days 1–5) and cisplatin (100 mg/m2 per 24 h on day 6), was administered, then a wide field of radiotherapy (36 Gy/20 fraction), chemotherapy, a shrinking field of radiotherapy (34 Gy/17 fraction), and chemotherapy were performed alternately. Between December 2003 and March 2006, 90 patients in 25 facilities were enrolled in this study, 87 patients were finally evaluated. A total of 67 patients (76.1%) completed the course of treatment. The overall survival and the progression-free survival rates at 5 years were 78.04% (95% CI: 69.1∼87.0%), and 68.74% (95% CI: 58.8∼78.7%), respectively. The long-term outcomes of ALCRT for NPC were thought to be promising. ALCRT will be considered to be a controlled trial to compare therapeutic results with those of concurrent chemoradiotherapy for NPC. PMID:25991077

  20. Positron Emission Tomography for Neck Evaluation Following Definitive Treatment with Chemoradiotherapy for Locoregionally Advanced Head and Neck Squamous Cell Carcinoma

    PubMed Central

    Bar-Ad, Voichita; Mishra, Mark; Ohri, Nitin; Intenzo, Charles

    2013-01-01

    Objectives The objective of the current review was to assess published data on the role of Positron Emission Tomography (PET) for evaluation of nodal residual disease after definitive chemoradiotherapy for head and neck squamous cell carcinoma (HNSCC). Methods Studies were identified by searching PubMed electronic databases. Only studies using a post-chemoradiotherapy PET for nodal residual disease evaluation were included in the present review. Both prospective and retrospective studies were included. Information regarding sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of PET for detecting nodal residual disease after definitive chemoradiotherapy for HNSCC was extracted and analyzed. Results Twenty published studies were included in the present review. Existing data suggest that a negative post-chemoradiotherapy PET scan is associated with a negative predictive value up to 100%. The sensitivity of PET in detecting nodal residual disease is greater for scans performed ≥ 10 weeks after definitive treatment with chemoradiotherapy for HNSCC. Conclusions Further studies are needed to quantify the reliability of PET in detecting nodal residual disease after chemoradiotherapy for locoregionally advanced HNSCC. The optimal timing of PET imaging after chemoradiotherapy remains to be defined. PMID:21864252

  1. Circulating Tumour Cells as an Independent Prognostic Factor in Patients with Advanced Oesophageal Squamous Cell Carcinoma Undergoing Chemoradiotherapy.

    PubMed

    Su, Po-Jung; Wu, Min-Hsien; Wang, Hung-Ming; Lee, Chia-Lin; Huang, Wen-Kuan; Wu, Chiao-En; Chang, Hsien-Kun; Chao, Yin-Kai; Tseng, Chen-Kan; Chiu, Tzu-Keng; Lin, Nina Ming-Jung; Ye, Siou-Ru; Lee, Jane Ying-Chieh; Hsieh, Chia-Hsun

    2016-01-01

    The role of circulating tumour cells (CTCs) in advanced oesophageal cancer (EC) patients undergoing concurrent chemoradiotherapy (CCRT) remains uncertain. A negative selection protocol plus flow cytometry was validated to efficiently identify CTCs. The CTC number was calculated and analysed for survival impact. The protocol's efficacy in CTC identification was validated with a recovery rate of 44.6 ± 9.1% and a coefficient of variation of 20.4%. Fifty-seven patients and 20 healthy donors were enrolled. Initial staging, first response to CRT, and surgery after CRT were prognostic for overall survival, with P values of <0.0001, <0.0001, and <0.0001, respectively. The CTC number of EC patients is significantly higher (P = 0.04) than that of healthy donors. Multivariate analysis for disease-specific progression-free survival showed that surgery after response to CCRT, initial stage, and CTC number (≥21.0 cells/mL) played independent prognostic roles. For overall survival, surgery after CCRT, performance status, initial stage, and CTC number were significant independent prognostic factors. In conclusion, a negative selection plus flow cytometry protocol efficiently detected CTCs. The CTC number before CCRT was an independent prognostic factor in patients with unresectable oesophageal squamous cell carcinoma. Further large-scale prospective studies for validation are warranted. PMID:27530152

  2. Contribution of the toxic advanced glycation end-products-receptor axis in nonalcoholic steatohepatitis-related hepatocellular carcinoma

    PubMed Central

    Takino, Jun-ichi; Nagamine, Kentaro; Hori, Takamitsu; Sakasai-Sakai, Akiko; Takeuchi, Masayoshi

    2015-01-01

    Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. The main etiologies of HCC are hepatitis B virus and hepatitis C virus (HCV), and non-hepatitis B/non-hepatitis C HCC (NBNC-HCC) has also been identified as an etiological factor. Although the incidence of HCV-related HCC in Japan has decreased slightly in recent years, that of NBNC-HCC has increased. The onset mechanism of NBNC-HCC, which has various etiologies, remains unclear; however, nonalcoholic steatohepatitis (NASH), a severe form of nonalcoholic fatty liver disease, is known to be an important risk factor for NBNC-HCC. Among the different advanced glycation end-products (AGEs) formed by the Maillard reaction, glyceraldehyde-derived AGEs, the predominant components of toxic AGEs (TAGE), have been associated with NASH and NBNC-HCC, including NASH-related HCC. Furthermore, the expression of the receptor for AGEs (RAGE) has been correlated with the malignant progression of HCC. Therefore, TAGE induce oxidative stress by binding with RAGE may, in turn, lead to adverse effects, such as fibrosis and malignant transformation, in hepatic stellate cells and tumor cells during NASH or NASH-related HCC progression. The aim of this review was to examine the contribution of the TAGE-RAGE axis in NASH-related HCC. PMID:26483867

  3. Circulating Tumour Cells as an Independent Prognostic Factor in Patients with Advanced Oesophageal Squamous Cell Carcinoma Undergoing Chemoradiotherapy

    PubMed Central

    Su, Po-Jung; Wu, Min-Hsien; Wang, Hung-Ming; Lee, Chia-Lin; Huang, Wen-Kuan; Wu, Chiao-En; Chang, Hsien-Kun; Chao, Yin-Kai; Tseng, Chen-Kan; Chiu, Tzu-Keng; Lin, Nina Ming-Jung; Ye, Siou-Ru; Lee, Jane Ying-Chieh; Hsieh, Chia-Hsun

    2016-01-01

    The role of circulating tumour cells (CTCs) in advanced oesophageal cancer (EC) patients undergoing concurrent chemoradiotherapy (CCRT) remains uncertain. A negative selection protocol plus flow cytometry was validated to efficiently identify CTCs. The CTC number was calculated and analysed for survival impact. The protocol’s efficacy in CTC identification was validated with a recovery rate of 44.6 ± 9.1% and a coefficient of variation of 20.4%. Fifty-seven patients and 20 healthy donors were enrolled. Initial staging, first response to CRT, and surgery after CRT were prognostic for overall survival, with P values of <0.0001, <0.0001, and <0.0001, respectively. The CTC number of EC patients is significantly higher (P = 0.04) than that of healthy donors. Multivariate analysis for disease-specific progression-free survival showed that surgery after response to CCRT, initial stage, and CTC number (≥21.0 cells/mL) played independent prognostic roles. For overall survival, surgery after CCRT, performance status, initial stage, and CTC number were significant independent prognostic factors. In conclusion, a negative selection plus flow cytometry protocol efficiently detected CTCs. The CTC number before CCRT was an independent prognostic factor in patients with unresectable oesophageal squamous cell carcinoma. Further large-scale prospective studies for validation are warranted. PMID:27530152

  4. Subcutaneous administration of interleukin 2 and interferon-alpha-2b in advanced renal cell carcinoma: a confirmatory study.

    PubMed Central

    Facendola, G.; Locatelli, M. C.; Pizzocaro, G.; Piva, L.; Pegoraro, C.; Pallavicini, E. B.; Signaroldi, A.; Meregalli, M.; Lombardi, F.; Beretta, G. D.

    1995-01-01

    Recent clinical studies have suggested that the combination of subcutaneous recombinant human interleukin 2 (rIL-2) and interferon alpha (rIFN-alpha) is especially promising in advanced renal cell carcinoma. We assessed the safety, activity and toxicity of home therapy with these two agents in 50 patients. Each treatment cycle consisted of a 2 day pulse phase, with 9 x 10(6) IU m-2 of rIL-2 being given subcutaneously every 12 h, followed by a 6 week maintenance phase during which rIL-2 1.8 x 10(6) IU m-2 was administered subcutaneously every 12 h on days 1-5 and rIFN-alpha 2b 5 x 10(6) IU m-2 once a day on days 1, 3 and 5. Objective responses (CR+PR) occurred in 9/50 (18%) patients, six of whom (12%) achieved a complete response. Disease stabilisation was observed in 17 cases (34%) and 18 patients progressed during therapy. In the other six cases, treatment was interrupted early for toxicity or patient refusal. One patient died of myocardial infarction during the second cycle. The overall median survival was 12 months. Home therapy with subcutaneous rIL-2 + rIFN-alpha 2b proved to be active, feasible and moderately toxic, but serious adverse events can sometimes occur. PMID:8519672

  5. Selection of a patient subgroup with advanced esophageal squamous carcinoma who could benefit from second-line chemotherapy.

    PubMed

    Kim, Seung Tae; Park, Kyong Hwa; Oh, Sang Cheul; Seo, Jae Hong; Shin, Sang Won; Kim, Jun Suk; Kim, Yeul Hong

    2010-01-01

    Despite first-line therapy, most patients with advanced esophageal squamous cell carcinoma (ESCC) experience disease progression and may become eligible for second-line chemotherapy. Although commonly used, the role of salvage chemotherapy in patients with recurrent or metastatic ESCC has not yet been established. We analyzed 53 patients who had received second-line chemotherapy after the failure of cisplatin-based combination chemotherapy with or without radiotherapy as first-line therapy in ESCC between March 2000 and June 2008. Median progression-free survival (PFS) and overall survival (OS) for second-line chemotherapy were 2.4 and 5.2 months, respectively, with an overall response rate of 18.9%. In multivariate analysis, Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 2 or more and PFS under first-line therapy <4 months were independent prognostic factors for decreased OS. OS was estimated based on the number of adverse prognostic factors: 0 = good; 1 = intermediate, and 2 = poor. The median OS for the good, intermediate, and poor prognostic groups were 11.2, 4.5 and 4.3 months, respectively (p < 0.001). The good prognostic group showed better OS than the intermediate or poor groups (p < 0.001). Second-line chemotherapy may be beneficial for OS in ESCC patients with ECOG PS 0-1 and PFS under first-line therapy ≥4 months.

  6. A combination of sorafenib and SC-43 is a synergistic SHP-1 agonist duo to advance hepatocellular carcinoma therapy.

    PubMed

    Chao, Tzu-I; Tai, Wei-Tien; Hung, Man-Hsin; Tsai, Ming-Hsien; Chen, Min-Hsuan; Chang, Mao-Ju; Shiau, Chung-Wai; Chen, Kuen-Feng

    2016-02-28

    Sorafenib is the first and currently the only standard treatment for advanced hepatocellular carcinoma (HCC). We previously developed a sorafenib derivative SC-43, which exhibits much more enhanced anti-HCC activity than sorafenib and also promotes apoptosis in sorafenib-resistant HCC cells. Herein, a novel "sorafenib plus" combination therapy was developed by coupling sorafenib treatment with SC-43. Both sorafenib and SC-43 are proven Src homology region 2 domain containing phosphatase 1 (SHP-1) agonists. The combined actions of sorafenib and SC-43 enhanced SHP-1 activity, which was associated with diminished STAT3-related signals and stronger expression of apoptotic genes above that of either drug alone, culminating in increased cell death. Decreased p-STAT3 signaling and tumor size, as well as increased SHP-1 activity were observed in mice receiving the combination therapy in a subcutaneous HCC model. More reduced orthotopic HCC tumor size and prolonged survival were also observed in mice in the combination treatment arm compared to mice in either of the monotherapy arms. These results in the preclinical setting pave the way for further clinical studies to treat unresectable HCC. PMID:26679051

  7. The long-term outcomes of alternating chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma: a multiinstitutional phase II study.

    PubMed

    Fuwa, Nobukazu; Kodaira, Takeshi; Daimon, Takashi; Yoshizaki, Tomokazu

    2015-08-01

    To examine the long-term outcomes of alternating chemoradiotherapy (ALCRT) for patients with locoregionally advanced nasopharyngeal carcinoma (NPC) and to assess the efficacy of ALCRT for NPC. Patients with stage IIB to IVB, ECOG PS 0-2, 18-70 years-old, and sufficient organ function were eligible for this study. First, chemotherapy, consisting of 5-fluorouracil (800 mg/m(2) per 24 h on days 1-5) and cisplatin (100 mg/m(2) per 24 h on day 6), was administered, then a wide field of radiotherapy (36 Gy/20 fraction), chemotherapy, a shrinking field of radiotherapy (34 Gy/17 fraction), and chemotherapy were performed alternately. Between December 2003 and March 2006, 90 patients in 25 facilities were enrolled in this study, 87 patients were finally evaluated. A total of 67 patients (76.1%) completed the course of treatment. The overall survival and the progression-free survival rates at 5 years were 78.04% (95% CI: 69.1~87.0%), and 68.74% (95% CI: 58.8~78.7%), respectively. The long-term outcomes of ALCRT for NPC were thought to be promising. ALCRT will be considered to be a controlled trial to compare therapeutic results with those of concurrent chemoradiotherapy for NPC.

  8. Targeted Therapy in Locally Advanced and Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (LA-R/M HNSCC)

    PubMed Central

    Echarri, María José; Lopez-Martin, Ana; Hitt, Ricardo

    2016-01-01

    Surgery and radiotherapy are the standard treatment options for patients with squamous cell carcinoma of the head and neck (SCCHN). Chemoradiotherapy is an alternative for patients with locally advanced disease. In recurrent/metastatic disease and after progression to platin-based regimens, no standard treatments other than best supportive care are currently available. Most SCCHN tumours overexpress the epidermal growth factor receptor (EGFR). This receptor is a tyrosine-kinase membrane receptor that has been implicated in angiogenesis, tumour progression and resistance to different cancer treatments. In this review, we analysed the different drugs and pathways under development to treat SCCHN, especially recurrent/metastatic disease. Until now, the EGFR signalling pathway has been considered the most important target with respect to new drugs; however, new drugs, such as immunotherapies, are currently under study. As new treatments for SCCHN are developed, the influence of therapies with respect to overall survival, progression free survival and quality of life in patients with this disease is changing. PMID:26927178

  9. Comparison of CT and PET-CT based planning of radiation therapy in locally advanced pancreatic carcinoma

    PubMed Central

    Topkan, Erkan; Yavuz, Ali A; Aydin, Mehmet; Onal, Cem; Yapar, Fuat; Yavuz, Melek N

    2008-01-01

    Background To compare computed tomography (CT) with co-registered positron emission tomography-computed tomography (PET-CT) as the basis for delineating gross tumor volume (GTV) in unresectable, locally advanced pancreatic carcinoma (LAPC). Methods Fourteen patients with unresectable LAPC had both CT and PET images acquired. For each patient, two three-dimensional conformal plans were made using the CT and PET-CT fusion data sets. We analyzed differences in treatment plans and doses of radiation to primary tumors and critical organs. Results Changes in GTV delineation were necessary in 5 patients based on PET-CT information. In these patients, the average increase in GTV was 29.7%, due to the incorporation of additional lymph node metastases and extension of the primary tumor beyond that defined by CT. For all patients, the GTVCT versus GTVPET-CT was 92.5 ± 32.3 cm3 versus 104.5 ± 32.6 cm3 (p = 0.009). Toxicity analysis revealed no clinically significant differences between two plans with regard to doses to critical organs. Conclusion Co-registration of PET and CT information in unresectable LAPC may improve the delineation of GTV and theoretically reduce the likelihood of geographic misses. PMID:18808725

  10. Paneth Cell in Adenomas of the Distal Colorectum Is Inversely Associated with Synchronous Advanced Adenoma and Carcinoma

    PubMed Central

    Mahon, Megan; Xu, Jie; Yi, Xianghua; Liu, Xiuli; Gao, Nan; Zhang, Lanjing

    2016-01-01

    Recent studies have linked appearance of Paneth cells in colorectal adenomas to adenoma burden and male gender. However, the clinical importance of Paneth cells’ associations with synchronous advanced adenoma (AA) and colorectal carcinoma (CRC) is currently unclear. We performed a comprehensive case-control study using 1,900 colorectal adenomas including 785 from females, and 1,115 from males. We prospectively reviewed and recorded Paneth cell status in the colorectal adenomas consecutively collected between February 2014 and June 2015. Multivariable logistic regression analyses revealed that, in contrast to the adenomas without Paneth cells, the Paneth cell-containing adenomas at distal colorectum were inversely associated with presence of a synchronous AA or CRC (odds ratio [OR] 0.39, P = 0.046), whereas no statistical significance was reached for Paneth cell-containing proximal colorectal adenomas (P = 0.33). Synchronous AA and CRC were significantly associated with older age (60 + versus <60 years, OR 1.60, P = 0.002), male gender (OR 1.42, P = 0.021), and a history of AA or CRC (OR 2.31, P < 0.001). However, synchronous CRC was not associated with Paneth cell status, or a history of AA or CRC. Paneth cell presence in the adenomas of distal colorectum may be a negative indicator for synchronous AA and CRC, and seems to warrant further studies. PMID:27188450

  11. Initial evidence for Sec62 as a prognostic marker in advanced head and neck squamous cell carcinoma

    PubMed Central

    WEMMERT, SILKE; LINDNER, YASMIN; LINXWEILER, JOHANNES; WAGENPFEIL, STEFAN; BOHLE, RAINER; NIEWALD, MARCUS; SCHICK, BERNHARD

    2016-01-01

    Head and neck squamous cell carcinoma (HNSCC) is a malignancy with an increasing incidence. To aid with the selection of the most appropriate therapy, biomarkers have become a specific research focus. Sec62 is involved in endoplasmic reticulum stress tolerance and cell migration, and has been identified as a novel prognostic marker for non-small cell lung cancer. In addition, Sec62 may be a promising candidate in HNSCC. Pretreatment biopsies of 35 patients with locally advanced HNSCC, who were treated with definitive chemoradiation therapy without prior surgery, were examined for the expression of Sec62 protein, as well as the expression of epidermal growth factor receptor (EGFR), p16 and survivin proteins. Immunohistological results were correlated with patient overall survival (OS) and progression-free survival (PFS) times. In the present patient cohort, 12/35 cases (34%) demonstrated strong and 8/35 cases (23%) moderate Sec62 staining intensity. Additionally, in 11/35 cases (31%), weak staining was observed, and only 4/35 cases (11%) were Sec62-negative. Notably, a high Sec62 protein level was associated with a significantly poorer OS and PFS (P=0.020 and P=0.028, respectively). Furthermore, higher nuclear survivin expression showed a weak trend for poorer OS rate (P=0.079), whilst neither cytoplasmic survivin, EGFR nor p16 influenced OS or PFS significantly. The present study indicated that Sec62 is a promising prognostic marker for HNSCC. Increased Sec62 protein expression may indicate a poorer prognosis in advanced HNSCC. As the present study was focused on patients treated by chemoradiation therapy, further studies with larger patient cohorts and alternative treatment approaches are required in order to define the prognostic value of Sec62 in HNSCC. PMID:26998059

  12. Effective hepatic artery chemoembolization for advanced hepatocellular carcinoma with multiple tumor thrombi and pulmonary metastases: A case report

    PubMed Central

    Huang, De-Jia; Li, Yan-Hao; Luo, Yao-Chang; Huang, Jun-Zhen; He, Hai-Yuan

    2016-01-01

    Advanced hepatocellular carcinoma (HCC) with tumor thrombi invading the portal vein and extending into the right atrium (RA) through the hepatic vein is regarded as a terminal-stage condition. Intracardiac tumor thrombus and treatment via liver resection has been reported in the current literature, but results from this therapeutic approach remain unsatisfactory. The present study describes a rare case of HCC with metastatic portal vein, middle hepatic vein, inferior vena cava (IVC) and RA tumor thrombi, and pulmonary metastases. A 29-year-old woman was admitted to The First Affiliated Hospital of Guangxi Traditional Chinese Medical University (Nanning, China) subsequent to experiencing right upper quadrant abdominal pain. Following diagnosis, based on computed tomography analysis and laboratory data, the patient underwent an initial transcatheter arterial chemoembolization (TACE) treatment using fluorouracil (5-FU), pirarubicin, mitomycin C, Lipiodol and sodium alginate microball (KMG). At 1 month post-treatment, serum α-fetoprotein levels remained at >1,000 ng/ml. Subsequently, the patient underwent a second TACE treatment. At 1 month after the second treatment, the abdominal pain had been alleviated and the serum α-fetoprotein levels were reduced to <20 ng/ml. Imaging analysis indicated a marked reduction in tumor burden in the liver and the hepatic vein and IVC tumor thrombi. Furthermore, the portal vein and RA tumor thrombi, and the pulmonary metastases had disappeared. At 40 months after the second TACE therapy, the patient remains alive without any signs of recurrence. The present case demonstrates that the administration of TACE, using 5-FU, pirarubicin, mitomycin C, Lipiodol and KMG, functions as an effective treatment in cases of unresectable advanced HCC presenting with pulmonary metastases and extensive tumor thrombi in the IVC, the RA and one branch of the portal vein. PMID:27602147

  13. [A case of advanced hepatocellular carcinoma successfully treated by liver resection after complete response induced by sorafenib administration].

    PubMed

    Kim, Yongkook; Hosoda, Yohei; Kakita, Naruyasu; Yamada, Yukinori; Yamasaki, Masaru; Nishino, Masaya; Okano, Miho; Nagai, Kenichi; Yasui, Masayoshi; Tsujinaka, Toshimasa

    2014-11-01

    A 50-year-old man presented to our hospital with the chief complaint of right hypochondriac pain and a palpable tumor. Advanced hepatocellular carcinoma (HCC) and chronic hepatitis B infection were diagnosed and treated by twice-repeated transcatheterarterial chemoembolization (TACE) followed by administration of entecavir. Two months after the last TACE, alpha-fetoprotein(AFP)and protein induced by vitamin K absence or antagonistII (PIVKA-II) levels had elevated, and multiple small early enhancing nodules were detected on computed tomography(CT)scan. Based on his age and liver function (Child-Pugh score A5), a full dose of sorafenib (800 mg/day) was administered. The sorafenib dose was decreased after one month to 400mg/day because of hand-foot syndrome. Following sorafenib administration, the lesions shrank markedly, and complete response (CR) according to modified Response Evaluation Criteria In Solid Tumors(mRECIST)was achieved within 4 months. Six months after sorafenib treatment was begun, recurrent HCC was detected in segment 6, near the previously treated lesion. The decreased size of the main tumor and normalization of AFP levels allowed curative surgical resection. The patient was discharged 5 days after surgery and is currently treated with a half dose of sorafenib. Thirteen months after surgery, a small early enhancing lesion is visible on postoperative CT scan, but AFP and PIVKA-II levels are still keeping in a normal range. This case demonstrates that if sorafenib treatment is effective, then subsequent surgical treatment can be reconsidered in patients with advanced HCC responding to this combined therapy. PMID:25731444

  14. Clinicopathological evaluation of pre-operative chemoradiotherapy with S-1 as a treatment for locally advanced oral squamous cell carcinoma

    PubMed Central

    KAWANO, SHINTARO; ZHENG, YANQUN; OOBU, KAZUNARI; MATSUBARA, RYOTA; GOTO, YUICHI; CHIKUI, TORU; YOSHITAKE, TADAMASA; KIYOSHIMA, TAMOTSU; JINNO, TEPPEI; MARUSE, YASUYUKI; MITATE, EIJI; KITAMURA, RYOJI; TANAKA, HIDEAKI; TOYOSHIMA, TAKESHI; SUGIURA, TSUYOSHI; NAKAMURA, SEIJI

    2016-01-01

    The administration of pre-operative chemotherapy with S-1 and concurrent radiotherapy at a total dose of 30 Gy was clinicopathologically evaluated as a treatment for locally advanced oral squamous cell carcinoma (OSCC) in the present study. The participants comprised 81 patients with OSCC, consisting of 29 patients with stage II disease, 12 patients with stage III disease and 40 patients with stage IV disease. All patients received a total radiation dose of 30 Gy in daily fractions of 2 Gy, 5 times a week, for 3 weeks, and the patients were concurrently administered S-1 at a dose of 80–120 mg, twice daily, over 4 consecutive weeks. Radical surgery was performed in all cases at 2–6 weeks subsequent to the end of pre-operative chemoradiotherapy. The most common adverse event was oropharyngeal mucositis, but this was transient in all patients. No severe hematological or non-hematological toxicities were observed. The clinical and histopathological response rates were 70.4 and 75.3%, respectively. Post-operatively, local failure developed in 6 patients (7.4%) and neck failure developed in 2 patients (2.5%). Distant metastases were found in 7 patients (8.6%). The overall survival rate, disease-specific survival rate and locoregional control rate at 5 years were 87.7, 89.9 and 90.6%, respectively. Locoregional recurrence occurred more frequently in patients that demonstrated a poor histopathological response compared with patients that demonstrated a good response (P<0.01). These results indicate that pre-operative S-1 chemotherapy with radiotherapy at a total dose of 30 Gy is feasible and effective for patients with locally advanced OSCC, and that little or no histopathological response may be a risk factor for locoregional recurrence in this treatment. PMID:27123119

  15. VX-970, Cisplatin, and Radiation Therapy in Treating Patients With Locally Advanced HPV-Negative Head and Neck Squamous Cell Carcinoma

    ClinicalTrials.gov

    2016-10-28

    Head and Neck Squamous Cell Carcinoma; Stage III Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage III Oropharyngeal Squamous Cell Carcinoma; Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma; Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVB Oropharyngeal Squamous Cell Carcinoma; Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVC Oropharyngeal Squamous Cell Carcinoma

  16. Value of quantitative pathological variables as prognostic factors in advanced ovarian carcinoma.

    PubMed Central

    Brinkhuis, M; Baak, J P; Meijer, G A; van Diest, P J; Mogensen, O; Bichel, P; Neijt, J P

    1996-01-01

    AIMS: To evaluate correlations among clinical, pathological, morphometric, stereological, and DNA flow cytometric variables and their prognostic value in advanced ovarian cancer. METHODS: Tissue was collected from 180 patients with advanced ovarian cancer. All 180 had undergone debulking surgery and were being treated with cisplatin. Long term follow up was available for all patients. The mitotic activity index (MAI), volume % of epithelium (VPE), mean nuclear area (MNA), standard deviation of the nuclear area (SDNA), estimates of volume weighted mean nuclear volume (nu v), and variables obtained from minimum spanning tree (MST) analysis were assessed in the least differentiated tumour section in each case. DNA flow cytometry was also performed. RESULTS: Quantitative pathological features differed significantly with respect to histological grade. The MAI, MNA, SDNA, and the number of points connected to three neighbours differed significantly among the different DNA ploidy groups. The VPE and number of points connected to two or three neighbours differed significantly between FIGO stages III and IV. Fifty two (29%) patients survived. FIGO stage, residual disease and SDNA had prognostic significance on both univariate and multivariate survival analysis. In patients with FIGO III stage disease and residual tumour nodes < or = 2 cm in diameter (67 patients, 29 (43%) survivors) a prognostic index was established based on SDNA and of the line length of the MST. The median survival time was not reached in a subgroup of patients with favourable prognosis (overall survival 57%). Median survival was 32 months for patients with an unfavourable index score (overall survival 28%). CONCLUSION: Morphometric variables have important additional value in predicting prognosis in patients with advanced ovarian cancer. PMID:8655681

  17. Ultrasonographic diagnosis of incompetent cervix. A case report.

    PubMed

    Acker, D B; Spitzberg, E H; Benacerraf, B; Sachs, B P; Friedman, E A

    1988-12-01

    The ultrasonographic findings of an incompetent cervix, the protrusion of the lower pole of the fetal membranes through the dilated internal os, may precede physical changes in the cervix. The symptoms at that time may be nonspecific. As this case report indicates, we believe that action--either close observation, conservative treatment or surgical intervention--should follow the detection of this condition. PMID:3063817

  18. Endoscopic OCT for imaging of uterine body and cervix pathologies

    NASA Astrophysics Data System (ADS)

    Shakhova, Natalia M.; Kuznetzova, Irina N.; Gladkova, Natalia D.; Snopova, Ludmila; Gelikonov, Valentin M.; Gelikonov, Grigory V.; Feldchtein, Felix I.; Kuranov, Roman V.; Sergeev, Alexander M.

    1998-04-01

    First results of endoscopic applications of optical coherence tomography (OCT) in gynecology are presented. We have studied mucosa of uterus, uterine cervix and vagina in vivo. Images of healthy endometrium in different stages of menstrual cycle have been recorded. For uterine cervix not only OCT data of normal state but some kids of pathology have been analyzed. Capability of OCT to identify alterations of mucosa makes this method promising for early diagnosis of tumors and precise guiding of excisional biopsy.

  19. Phase 2 Study of Combined Sorafenib and Radiation Therapy in Patients With Advanced Hepatocellular Carcinoma

    SciTech Connect

    Chen, Shang-Wen; Lin, Li-Ching; Kuo, Yu-Cheng; Liang, Ji-An; Kuo, Chia-Chun; Chiou, Jeng-Fong

    2014-04-01

    Purpose: This phase 2 study evaluated the efficacy of radiation therapy (RT) with concurrent and sequential sorafenib therapy in patients with unresectable hepatocellular carcinoma (HCC). Methods and Materials: Forty patients with unresectable HCC unfit for transarterial chemoembolization were treated with RT with concurrent and sequential sorafenib. Sorafenib was administered from the commencement of RT at a dose of 400 mg twice daily and continued to clinical or radiologic progression, unacceptable adverse events, or death. All patients had underlying Child-Pugh A cirrhosis. The maximal tumor diameter ranged from 3.0 cm to 15.5 cm. Coexisting portal vein thrombosis was found in 24 patients and was irradiated simultaneously. The cumulative RT dose ranged from 40 Gy to 60 Gy (median, 50 Gy). Image studies were done 1 month after RT and then every 3 months thereafter. Results: Thirty-three (83%) completed the allocated RT. During RT, the incidence of hand-foot skin reactions ≥ grade 2 and diarrhea were 37.5% and 25%, respectively, and 35% of patients had hepatic toxicities grade ≥2. Twenty-two (55.0%) patients achieved complete or partial remission at the initial assessment, and 18 (45%) had stable or progressive disease. The 2-year overall survival and infield progression-free survival (IFPS) were 32% and 39%, respectively. A Cancer of the Liver Italian Program (CLIP) score ≥2 was associated with an inferior outcome in overall survival. Six patients (15%) developed treatment-related hepatic toxicity grade ≥3 during the sequential phase, and 3 of them were fatal. Conclusions: When RT and sorafenib therapy were combined in patients with unresectable HCC, the initial complete or partial response rate was 55% with a 2-year IFPS of 39%. A CLIP score ≥2 was associated with an inferior outcome in overall survival. Hepatic toxicities are a major determinant of the safety; the combination should be used with caution and needs further investigation.

  20. Advances in diagnosis, treatment and palliation of pancreatic carcinoma: 1990-2010

    PubMed Central

    Sharma, Chakshu; Eltawil, Karim M; Renfrew, Paul D; Walsh, Mark J; Molinari, Michele

    2011-01-01

    Several advances in genetics, diagnosis and palliation of pancreatic cancer (PC) have occurred in the last decades. A multidisciplinary approach to this disease is therefore recommended. PC is relatively common as it is the fourth leading cause of cancer related mortality. Most patients present with obstructive jaundice, epigastric or back pain, weight loss and anorexia. Despite improvements in diagnostic modalities, the majority of cases are still detected in advanced stages. The only curative treatment for PC remains surgical resection. No more than 20% of patients are candidates for surgery at the time of diagnosis and survival remains quite poor as adjuvant therapies are not very effective. A small percentage of patients with borderline non-resectable PC might benefit from neo-adjuvant chemoradiation therapy enabling them to undergo resection; however, randomized controlled studies are needed to prove the benefits of this strategy. Patients with unresectable PC benefit from palliative interventions such as biliary decompression and celiac plexus block. Further clinical trials to evaluate new chemo and radiation protocols as well as identification of genetic markers for PC are needed to improve the overall survival of patients affected by PC, as the current overall 5-year survival rate of patients affected by PC is still less than 5%. The aim of this article is to review the most recent high quality literature on this topic. PMID:21412497

  1. Treatment of metastatic and recurrent cervix cancer with chemotherapy: a randomised trial comparing hydroxyurea with cisdiamminedichloro-platinum plus methotrexate.

    PubMed

    Bezwoda, W R; Nissenbaum, M; Derman, D P

    1986-01-01

    In a randomised trial comparing single-agent chemotherapy (hydroxyurea) to combination chemotherapy in advanced cervix cancer, response was seen in 57% (including 13% CR) of patients receiving the combination (DDP + MTX) regimen. Responding patients survived significantly longer (11 months) than either those receiving hydroxyurea or those not responding to combination chemotherapy (4 months). Two patients remain in complete remission for 14+ and 17+ months.

  2. Enterocutaneous fistula 3 years after resection of an advanced gallbladder carcinoma

    PubMed Central

    Alkhalili, Eyas; Falk, Gavin A; Morris-Stiff, Gareth; Cameron, John

    2014-01-01

    A 71-year-old woman presented to the emergency department with abdominal pain and fever. Her surgical history was significant for gallbladder adenocarcinoma for which she had undergone extensive resection 32 months previously. At that time she underwent cholecystectomy, wedge resection of the liver, pancreatoduodenectomy, right nephrectomy and right hemicolectomy for a locally advanced gallbladder adenocarcinoma. Examination revealed a tender, warm, upper midline abdominal wall mass. A CT scan with oral contrast revealed a fistulous tract extending from the gastrojejunostomy (GJ) into an abscess cavity in the adjacent anterior abdominal wall. She underwent open wound drainage with debridement, and was started on parenteral nutrition and intravenous antibiotics. The patient then underwent surgical repair excision of the fistula and refashioning of the GJ 1 month later. Histological examination of the specimen revealed well-healed suture lines, and no evidence of tumour recurrence. PMID:24395877

  3. Sunitinib, Cetuximab, and Radiation Therapy in Treating Patients With Locally Advanced or Recurrent Squamous Cell Carcinoma of the Head and Neck

    ClinicalTrials.gov

    2013-07-01

    Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Salivary Gland Squamous Cell Carcinoma; Stage III Salivary Gland Cancer; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage III Verrucous Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IV Salivary Gland Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IV Verrucous Carcinoma of the Larynx; Stage IV Verrucous Carcinoma of the Oral Cavity; Tongue Cancer; Untreated Metastatic Squamous Neck Cancer With Occult Primary

  4. [Uterine cervix cancer. Clinical stage III. Combined radiotherapy and chemotherapy treatment].

    PubMed

    Ayala Hernández, J R; de la Huerta Sánchez, R; Morales Canfield, F; Fernández Orozco, A

    1991-07-01

    55 patients with stage III carcinoma of the uterine cervix were entered into a prospective randomized study to evaluate the possible radiation-potentiating properties of bleomycin. Group A received classical radiation treatment with telecobalt-therapy 50 Gy/25 fractions plus 32 Gy/4 fractions (Cathetron). The other two groups received 15 mg of bleomycin by continue infusion two time of week during 5 week, groups B before, and group C after, irradiation. The morbidity was minimal. The initial response was complete in 49 cases and partial in 6 cases. At 2 years there were 26 recurrences, 22 (88.8%), locoregional recurrences and 4 distant metastasis, 3 in the group of bleomycin treatment. The probability of actuarial survival was 62.1%, 30.1% and 35.6% respectively to groups A, B and C. Addition of bleomycin to radiotherapy failed to increase the recurrence-free survival.

  5. Budget impact analysis of first-line treatment with pazopanib for advanced renal cell carcinoma in Spain

    PubMed Central

    2013-01-01

    Background Due to economic constraints, cancer therapies are under close scrutiny by clinicians, pharmacists and payers alike. There is no published pharmacoeconomic evidence guiding the choice of first-line therapy for advanced renal cell carcinoma (RCC) in the Spanish setting. We aimed to develop a model describing the natural history of RCC that can be used in healthcare decision-making. We particularly analyzed the budget impact associated with the introduction of pazopanib compared to sunitinib under the Spanish National Healthcare System (NHS) perspective. Methods We developed a Markov model to estimate the future number of cases of advanced RCC (patients with favorable or intermediate risk) resulting either from initial diagnosis or disease progression after surgery. The model parameters were obtained from the literature. We assumed that patients would receive either pazopanib or sunitinib as first-line therapy until disease progression. Pharmacological costs and costs associated with the management of adverse events (AE) were considered. A univariate sensitivity analysis was undertaken in order to test the robustness of the results. Results The model predicted an adult RCC prevalence of 7.5/100,000 (1-year), 20.7/100,000 (3-year) and 32.5/100,000 (5-year). These figures are very close to GLOBOCAN reported RCC prevalence estimates of 7.6/100,000, 20.2/100,000 and 31.1/100,000, respectively. The model predicts 1,591 advanced RCC patients with favorable or intermediate risk in Spain in 2013. Annual per patient pharmacological costs were €32,365 and €39,232 with pazopanib and sunitinib, respectively. Annual costs associated with the management of AE were €662 and €974, respectively. Overall annual per patient costs were €7,179 (18%) lower with pazopanib compared to sunitinib. For every point increase in the percentage of patients treated with pazopanib, the NHS would save €67,236. If all the 1,591 patients predicted were treated with pazopanib, the

  6. Cine MRI of swallowing in patients with advanced oral or oropharyngeal carcinoma: a feasibility study.

    PubMed

    Kreeft, Anne Marijn; Rasch, Coen R N; Muller, Sara H; Pameijer, Frank A; Hallo, Eeke; Balm, Alfons J M

    2012-06-01

    Treatment of oral and oropharyngeal cancer may cause dysphagia. Purpose is to examine whether cine magnetic resonance imaging (MRI) yields additional information compared to standard examination in the evaluation of posttreatment dysphagia and mobility of oral and oropharyngeal structures. Thirty-four cine MRIs were made in 23 patients with advanced oral and oropharyngeal cancer, consisting of an MR image every 800 ms during swallowing which is compared to videofluoroscopy and quality of life questionnaires. A scoring system was applied to assess mobility on cine MR and videofluoroscopy leading to a score ranging from 9 to 17. Cine MRI of the swallowing in a midsagittal plane visualized the tumor (if located in the same plane), important anatomic structures and surgical reconstructions. Posttreatment mobility on cine MRI and videofluoroscopy was significantly diminished compared to pretreatment, mean pretreatment cine MRI score was 10.8 and posttreatment 12.4 (p = 0.017). Impaired mobility on cine MRI was significantly correlated to more swallowing problems (Spearman's correlation coefficient 0.73, p = 0.04), on videofluoroscopy not. Cine MRI is a promising new technique as an adjunct to standard examinations for evaluation of swallowing in patients with oral and oropharyngeal cancer. Cine MRI directly visualizes the dynamics of swallowing and allows evaluation of pre- and posttreatment differences. Abnormal findings are significantly correlated with subjective swallowing complaints of patients.

  7. Accelerated fractionation radiation therapy for advanced squamous cell carcinoma of the head and neck

    SciTech Connect

    Giri, P.G.; Gemer, L.S. )

    1991-09-01

    The authors treated 14 patients who had advanced head and neck cancer with an accelerated fractionation schedule of irradiation consisting of two fractions given 6 hours apart. In the morning a volume of 1.7 Gy was given to an area that encompassed the entire tumor, enlarged lymph nodes, and all areas at risk for microscopic disease. Six hours later, 1.1 Gy was given to an area that included only the tumor and any enlarged lymph nodes, with a 2-cm margin. The treatment was well tolerated; of the 13 patients who completed therapy, six did not require a break in therapy, and seven patients did. The median rest period was 2 days. There was no grade 4 toxicity. Grade 3 toxicity included skin changes (one case), mucositis (two), dysphagia (two), weight loss (three), and a decrease in the hemoglobin level (one case). The response rate in the 13 who completed therapy was 13/13 (100%); 11 of the 13 (83%) had a complete response. Only one of the 11 who achieved a complete response had failure at the primary site. At a median follow-up of 24 months, the absolute survival was 7/13 (54%) and the corrected survival was 7/10 (70%). This technique permits radiation therapy to be given on an accelerated schedule without a planned break in treatment. The overall response rate and survival at 2 years was excellent.

  8. A Phase II Study of Cixutumumab (IMC-A12, NSC742460) in Advanced Hepatocellular Carcinoma

    PubMed Central

    Abou-Alfa, Ghassan K.; Capanu, Marinela; O’Reilly, Eileen M.; Ma, Jennifer; Chou, Joanne F.; Gansukh, Bolorsukh; Shia, Jinru; Kalin, Marcia; Katz, Seth; Abad, Leslie; Reidy-Lagunes, Diane L.; Kelsen, David P.; Chen, Helen X.; Saltz, Leonard B.

    2014-01-01

    Background and Aims IGF-IR is implicated in hepatic carcinogenesis. This and preliminary evidence of biological activity of anti-IGF-1R monoclonal antibody cixutumumab in phase I trials prompted this phase II study. Methods Patients with advanced HCC, Child-Pugh A-B8, received cixutumumab 6 mg/kg weekly, in a Simon two-stage design study, with the primary endpoints being 4-month PFS and RECIST-defined response rate. Tissue and circulating markers plus different HCC scoring systems were evaluated for correlation with PFS and OS. Results As a result of pre-specified futility criteria, only stage 1 was accrued: N= 24: median age 67.5 years (range 49–83), KPS 80% (70–90%), 20 males (83%), 9 stage III (37%)/15 stage IV (63%), 18 Child-Pugh A (75%), 11 HBV (46%) /10 HCV (42%)/11 alcoholic cirrhosis (46%)/2 NASH (8%), 11 (46%) diabetic. Median number of doses: 7 (range 1–140). Grade 3/4 toxicities > 10% included: diabetes, elevated liver function tests, hyponatremia, and lymphopenia. Four-month PFS was 30% (95% CI 13–48), and there were no objective responses. Median overall survival was 8 months (95%CI 5.8– 14). IGF-R1 staining did not correlate with outcome. Elevated IGFBP-1 correlated with improved PFS (1.2 [95%CI 1–1.4]; p 0.009) and OS (1.2 [95%CI 1.1–1.4]; p 0.003). Conclusions Cixutumumab monotherapy did not have clinically meaningful activity in this unselected HCC population. Grade 3–4 hyperglycemia occurred in 46% of patients. Elevated IGFBP-1 correlated with improved PFS and OS. PMID:24045151

  9. Survival analysis of patients with advanced-stage nasopharyngeal carcinoma according to the Epstein-Barr virus status

    PubMed Central

    Peng, Hao; Chen, Lei; Zhang, Yuan; Guo, Rui; Li, Wen-Fei; Mao, Yan-Ping; Tan, Ling-Long; Sun, Ying; Zhang, Fan; Liu, Li-Zhi; Tian, Li; Lin, Ai-Hua; Ma, Jun

    2016-01-01

    Purpose The main aim of this study is to analyze the prognostic differences in nasopharyngeal carcinoma (NPC) patients who are positive and negative for Epstein-Barr virus (EBV). Results Of the 1106 patients, 248 (22.4%) had undetectable pre-treatment plasma EBV DNA levels. The total distant metastasis rate for EBV-negative group vs. EBV-positive group were 3.6% (9/248) vs. 15.0% (128/858) (P < 0.001). The estimated 4-year disease-free survival (DFS), overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRRFS) for EBV-negative group vs. EBV-positive group were 88.9% vs. 76.9% (P < 0.001), 93.6% vs. 85.9% (P = 0.001), 96.7% vs. 84.8% (P < 0.001) and 94.1% vs. 90.0% (P = 0.1), respectively. Multivariate analysis revealed that the EBV status was an independent prognostic factor for DFS (HR, 1.813; 95% CI, 1.219-2.695; P = 0.003), OS (HR, 1.828; 95% CI, 1.075-3.107; P = 0.026) and DMFS (HR, 3.678; 95% CI, 1.859-7.277; P <0.001), and overall stage still remained the most important prognostic factor in patients with stage III-IVB NPC. Methods and Materials Data on 1106 patients with non-metastatic, histologically proven advanced-stage (III-IVB) NPC who underwent intensity-modulated radiotherapy (IMRT) were retrospectively reviewed. Patient survival between different EBV status groups were compared. Conclusions EBV status was an independent prognostic factor for patients with stage III–IVB NPC. Neoadjuvant chemotherapy (NCT) plus concurrent chemoradiotherapy (CCRT) should be better treatment regimen for EBV-positive patients since distant metastasis was the main failure pattern, and CCRT may be enough for EBV-negative patients. PMID:27008701

  10. Preoperative Intensity Modulated Radiation Therapy and Chemotherapy for Locally Advanced Vulvar Carcinoma: Analysis of Pattern of Relapse

    SciTech Connect

    Beriwal, Sushil; Shukla, Gaurav; Shinde, Ashwin; Heron, Dwight E.; Kelley, Joseph L.; Edwards, Robert P.; Sukumvanich, Paniti; Richards, Scott; Olawaiye, Alexander B.; Krivak, Thomas C.

    2013-04-01

    Purpose: To examine clinical outcomes and relapse patterns in locally advanced vulvar carcinoma treated using preoperative chemotherapy and intensity modulated radiation therapy (IMRT). Methods and Materials: Forty-two patients with stage I-IV{sub A} (stage I, n=3; stage II, n=13; stage III, n=23; stage IV{sub A}, n=3) vulvar cancer were treated with chemotherapy and IMRT via a modified Gynecological Oncology Group schema using 5-fluorouracil and cisplatin with twice-daily IMRT during the first and last weeks of treatment or weekly cisplatin with daily radiation therapy. Median dose of radiation was 46.4 Gy. Results: Thirty-three patients (78.6%) had surgery for resection of vulva; 13 of these patients also had inguinal lymph node dissection. Complete pathologic response was seen in 48.5% (n=16) of these patients. Of these, 15 had no recurrence at a median time of 26.5 months. Of the 17 patients with partial pathological response, 8 (47.1%) developed recurrence in the vulvar surgical site within a median of 8 (range, 5-34) months. No patient had grade ≥3 chronic gastrointestinal/genitourinary toxicity. Of those having surgery, 8 (24.2%) developed wound infections requiring debridement. Conclusions: Preoperative chemotherapy/IMRT was well tolerated, with good pathologic response and clinical outcome. The most common pattern of recurrence was local in patients with partial response, and strategies to increase pathologic response rate with increasing dose or adding different chemotherapy need to be explored to help further improve outcomes.

  11. Sorafenib Tosylate With or Without Doxorubicin Hydrochloride in Treating Patients With Locally Advanced or Metastatic Liver Cancer

    ClinicalTrials.gov

    2016-06-20

    Adult Hepatocellular Carcinoma; Advanced Adult Hepatocellular Carcinoma; BCLC Stage C Adult Hepatocellular Carcinoma; BCLC Stage D Adult Hepatocellular Carcinoma; Localized Non-Resectable Adult Liver Carcinoma; Recurrent Adult Liver Carcinoma

  12. The Efficacy of Continued Sorafenib Treatment after Radiologic Confirmation of Progressive Disease in Patients with Advanced Hepatocellular Carcinoma

    PubMed Central

    2016-01-01

    Background Whether radiologically detected progressive disease (PD) is an accurate metric for discontinuing sorafenib treatment in patients with hepatocellular carcinoma (HCC) is unclear. We investigated the efficacy of sorafenib treatment after radiologic confirmation of PD in patients with advanced HCC. Methods We retrospectively analyzed HCC patients treated with sorafenib at Kyushu Medical Center. Six of the 92 patients with radiologically confirmed PD were excluded because they were classified as Child-Pugh C or had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥3; 86 patients were ultimately enrolled. Results Among the 86 patients, 47 continued sorafenib treatment after radiologic confirmation of PD (the continuous group), whereas 39 did not (the discontinuous group). The median survival time (MST) in the continuous group after confirmation was 12.9 months compared with 4.5 months in the discontinuous group (p <0.01). The time to progression in the continuous group after confirmation was 2.6 months compared with 1.4 months in the discontinuous group (p <0.01); it was 4.2 months and 2.1 months in patients who had received sorafenib ≥4 months and <4 months, respectively, before confirmation (p = 0.03). In these subgroups, the post-PD MST was 16.7 months and 9.6 months, respectively (p < 0.01). Independent predictors of overall survival after radiologic detection of PD were (hazard ratio, confidence interval): ECOG PS <2 (0.290, 0.107–0.880), Barcelona Clinical Liver Cancer stage B (0.146, 0.047–0.457), serum α-fetoprotein level ≥400 ng/mL (2.801, 1.355–5.691), and post-PD sorafenib administration (0.279, 0.150–0.510). Conclusion Continuing sorafenib treatment after radiologic confirmation of PD increased survival in patients with advanced HCC. Therefore, radiologically detected PD is not a metric for discontinuation of sorafenib treatment in such patients. PMID:26745625

  13. Shear Wave Speed Estimation in the Human Uterine Cervix

    PubMed Central

    Carlson, Lindsey C.; Feltovich, Helen; Palmeri, Mark L.; Dahl, Jeremy J.; del Rio, Alejandro Munoz; Hall, Timothy J.

    2014-01-01

    Objectives Our goals were to explore the spatial variability within the cervix and the sensitivity of shear wave speeds (SWS) to assess softness/stiffness differences in ripened (softened) versus unripened tissue. Methods We obtained SWS estimates from hysterectomy specimens (n=22), a subset of which were ripened (n = 13). Multiple measurements were made longitudinally along the cervical canal on both the anterior and posterior sides of the cervix. Statistical tests of differences in the proximal vs. distal, anterior vs. posterior, and ripened vs. unripened cervix were performed with individual two-sample t-tests and a linear mixed model. Results We discovered that SWS estimates monotonically increase from distal to proximal longitudinally along the cervix, that they also vary in the anterior compared to the posterior cervix, and that they are significantly different in ripened vs. unripened cervical tissue. Specifically, the mid position SWS estimates for the unripened group were 3.45±0.95 m/s (anterior) and 3.56±0.92 m/s (posterior), and 2.11±0.45 m/s (anterior) and 2.68±0.57 m/s (posterior) for the ripened (p<0.001). Conclusions We propose that shear wave speed estimation may be a valuable research and, ultimately, diagnostic tool for objective quantification of cervical stiffness/softness. PMID:23836486

  14. [Examination of the uterine cervix using the scanning electron microscope].

    PubMed

    Lerat, M F; Magre, J; Connehaye, P; Lerat, H; Barreau, A

    1975-01-01

    Scanning by electron microscopy of the cervix of the uterus allows us to study the various aspects, both normal and pathological, as well as the architecture of sections of the organ. All the same, as in all practical examinations carried out using scanning we have to beware of pictures that are but artefacts due to the method of preparation. The views obtained from a normal cervix of from pathological cervices show very different aspects. In the normal cervix the surfaces are more or less smooth and the architecture of the deeper levels shows a thick and regular texture. Infectious lesions of the outer aspect of the cervix show punched-out patterns, like craters, which penetrate more or less deeply into the sub-epithelial plane. While cervical dysplasia shows little except perhaps a more or less bossed-up epithelial surface, cancer of the cervix on the other hand shows a pavement pattern which is irregular. The pavements are formed by buds which are separated by faults which are more or less deep. In section the structures show a degree of disorientation in the texture. After treatment with radium the appearance is rather like ground glass of spiders webs and the architecture of the structures seems to be pock-marked and chaotic.

  15. Denileukin Diftitox Used in Treating Patients With Advanced Refractory Ovarian Cancer, Primary Peritoneal Carcinoma, or Epithelial Fallopian Tube Cancer

    ClinicalTrials.gov

    2016-05-02

    Fallopian Tube Cancer; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Epithelial Carcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Peritoneal Cavity Cancer; Recurrent Ovarian Epithelial Cancer; Stage III Ovarian Epithelial Cancer; Stage IV Ovarian Epithelial Cancer

  16. Can examination of the cervix provide useful information for prediction of cervical incompetence and following preterm labour?

    PubMed

    Rocco, B P; Garrone, C

    1999-08-01

    Diagnosing cervical incompetence is difficult because there are no specific tests or criteria that confirm or exclude the diagnosis, and the accurate prediction and diagnosis of preterm labour continue to frustrate the clinician. To evaluate the condition of the cervical canal, when dilatation of the internal os is identifiable by digital examination, cervical ripening has advanced considerably. Measurement of cervical length by ultrasonography offers the possibility of confirming cervical canal shortening before it is evident by digital examination. Transabdominal observations require a full urinary bladder, and the uterus is consequently deformed from the lower part to the fetal head. Measurement of cervical length by transvaginal ultrasonography has made it possible to resolve the problems associated with transabdominal observation and to assess the condition of the cervical canal in more detail. Application of transfundal pressure during transvaginal ultrasound evaluation of the cervix and its internal os may assist in detecting the asymptomatic incompetent cervix. PMID:10554937

  17. Automatic detection of anatomical landmarks in uterine cervix images.

    PubMed

    Greenspan, Hayit; Gordon, Shiri; Zimmerman, Gali; Lotenberg, Shelly; Jeronimo, Jose; Antani, Sameer; Long, Rodney

    2009-03-01

    The work focuses on a unique medical repository of digital cervicographic images ("Cervigrams") collected by the National Cancer Institute (NCI) in longitudinal multiyear studies. NCI, together with the National Library of Medicine (NLM), is developing a unique web-accessible database of the digitized cervix images to study the evolution of lesions related to cervical cancer. Tools are needed for automated analysis of the cervigram content to support cancer research. We present a multistage scheme for segmenting and labeling regions of anatomical interest within the cervigrams. In particular, we focus on the extraction of the cervix region and fine detection of the cervix boundary; specular reflection is eliminated as an important preprocessing step; in addition, the entrance to the endocervical canal (the "os"), is detected. Segmentation results are evaluated on three image sets of cervigrams that were manually labeled by NCI experts.

  18. Erlotinib in Treating Patients With Advanced Non-Small Cell Lung Cancer, Ovarian Cancer, or Squamous Cell Carcinoma of the Head and Neck

    ClinicalTrials.gov

    2013-01-08

    Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage IIIA Non-small Cell Lung Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx

  19. [Successful treatment of locally advanced squamous cell carcinoma of the esophagus by combination chemotherapy with 5-fluorouracil plus nedaplatin following tracheal stent tube placement-a case report].

    PubMed

    Nishimura, Junya; Kubo, Naoshi; Lee, Tomohiro; Shinto, Osamu; Sakurai, Katsunobu; Toyokawa, Takahiro; Tanaka, Hiroaki; Muguruma, Kazuya; Shibutani, Masatsune; Yamazoe, Sadaaki; Nagahara, Hisashi; Kimura, Kenjiro; Amano, Ryosuke; Ohtani, Hiroshi; Yashiro, Masakazu; Maeda, Kiyoshi; Ohira, Masaichi; Hirakawa, Kosei

    2013-11-01

    The patient was a 68-year-old man who complained of hoarseness and dyspnea. Upper gastrointestinal endoscopy revealed a type 3 tumor located in the middle thoracic esophagus at 30 cm from the incisor tooth that involved one-fourth of the circumference of the esophagus. Histopathological examination revealed moderately differentiated squamous cell carcinoma. Chest computed tomography( CT) revealed severe tracheal stenosis due to compression by a metastatic lymph node along the left recurrent laryngeal nerve. The patient was diagnosed as having cT4( 106recL-trachea), N2( 101L, 106recL, 106recR), M0, Stage IVa unresectable esophageal carcinoma. After insertion of a tracheal stent tube( spiral Z stent: diameter, 18 mm; length, 80 mm) to improve dyspnea, combination chemotherapy with 5-fluorouracil( 5-FU) plus nedaplatin was administered. Subsequent CT and endoscopy showed that the main tumor and the metastatic lymph node had significantly reduced in size and that complete response (CR) had been achieved. Thirty months after the initial treatment, the patient showed no sign of disease recurrence, after completion of 19 cycles of chemotherapy. The patient did not experience any severe adverse events. We report a case of a patient with locally advanced squamous cell carcinoma of the esophagus successfully treated with 5-FU/nedaplatin combination chemotherapy following tracheal stent tube placement.

  20. Phase I/II Study of Postoperative Adjuvant Chemoradiation for Advanced-Stage Cutaneous Squamous Cell Carcinoma of the Head and Neck (cSCCHN)

    ClinicalTrials.gov

    2014-11-17

    Recurrent Skin Cancer; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Squamous Cell Carcinoma of the Skin; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity

  1. Early Clinical Response after 2 Weeks of Sorafenib Therapy Predicts Outcomes and Anti-Tumor Response in Patients with Advanced Hepatocellular Carcinoma

    PubMed Central

    Kuzuya, Teiji; Ishigami, Masatoshi; Ishizu, Yoji; Honda, Takashi; Hayashi, Kazuhiko; Katano, Yoshiaki; Hirooka, Yoshiki; Ishikawa, Tetsuya; Nakano, Isao; Goto, Hidemi

    2015-01-01

    Background & Aims We evaluated the relationship between the early clinical response after 2 weeks of sorafenib therapy and the outcomes and anti-tumor response in patients with advanced hepatocellular carcinoma. Methods Fifty-seven patients who had intrahepatic hypervascular hepatocellular carcinoma and Child-Pugh (CP) class A disease at baseline were enrolled in this prospective, multicenter, observational, non-interventional study. As an early clinical response after 2 weeks of sorafenib therapy, changes in intra-tumor blood flow on contrast-enhanced computed tomography (CE-CT), alpha-fetoprotein (AFP) levels, and remnant liver function were investigated. Results After 2 weeks of sorafenib therapy, there were 26 patients (45.6%) without disappearance of arterial tumor enhancement on CE-CT, 15 patients (26.3%) with an AFP ratio of >1.2, and seven patients (12.3%) with two or more increments in the CP score. Multivariate analysis showed that the absence of disappearance of arterial tumor enhancement on CE-CT, AFP ratio of >1.2, and two or more increments in the CP score after 2 weeks of sorafenib therapy were significant and independent predictors of worse survival. Upon scoring these three variables as "poor prognostic factors", patients with poor prognostic score 4, 3 or 2 (n = 17) had significantly worse outcomes and a significantly higher progressive disease (PD) rate based on modified Response Evaluation Criteria in Solid Tumors at 6 weeks after sorafenib therapy than those with poor prognostic score 1 or 0 (n = 40) (median overall survival: 194 days vs. 378 days; p = 0.0010, PD rate: 70.6% vs. 20.0%; p = 0.0003, respectively). Conclusions Changes in intra-tumor blood flow on CE-CT, AFP levels, and remnant liver function after 2 weeks of sorafenib therapy may be useful for predicting the outcomes and anti-tumor response to sorafenib in patients with advanced hepatocellular carcinoma. PMID:26421430

  2. A Prospective Comparative Study of the Toxicity Profile of 5-Flurouracil, Adriamycin, Cyclophosphamide Regime VS Adriamycin, Paclitaxel Regime in Patients with Locally Advanced Breast Carcinoma

    PubMed Central

    Pillai, Pradeep Sadasivan; Jayakumar, Krishnan Nair Lalithamma

    2015-01-01

    Introduction A 5-flurouracil, Adriamycin, Cyclophosphamide (FAC) and Adriamycin, Paclitaxel (AT) are two popular chemotherapeutic regimens for treatment of breast carcinoma. The most time tested and popular regimen is FAC. It is extensively studied for efficacy and toxicity. But data regarding toxicity profile and efficacy of AT regimen is sparse. Aim To study the toxicity profile, severity of toxicities and clinical response rate of FAC and AT regimens in patients with locally advanced breast carcinoma. Materials and Methods A prospective observational study with 50 patients in each treatment arm. Study duration was 12 months from November 2012 to October 2013. Consecutive patients with locally advanced breast carcinoma receiving treatment with either FAC or AT regimen, satisfying inclusion criteria were enrolled into the study after getting informed written consent. Prior to initiation of treatment detailed medical history was taken from all patients. General clinical examination, examination of organ systems and local examination of breast lump were done. After each cycle of chemotherapy and after completion of treatment patients were interviewed and examined for clinical response and toxicities. Toxicities were graded with WHO toxicity grading criteria. All data were entered in a structured proforma. At least 50% reduction in tumour size was taken as adequate clinical response. Statistical Analysis Data was analysed using Chi-square test with help of Excel 2007 and SPSS-16 statistical software. Results Different pattern of toxicities were seen with FAC and AT regimens. Anaemia, thrombocytopenia, stomatitis, hyperpigmentation, photosensitivity and diarrhoea were more common with patients receiving FAC regimen. Leucopenia, peripheral neuropathy, myalgia, arthralgia, vomiting and injection site reactions were more common in AT regimen. Both FAC and AT regimens gave 100% clinical response. Conclusion FAC and AT regimens are equally efficacious but have different

  3. Cetuximab concurrent with IMRT versus cisplatin concurrent with IMRT in locally advanced nasopharyngeal carcinoma: A retrospective matched case-control study.

    PubMed

    Wu, Xin; Huang, Jingwen; Liu, Lei; Li, Hongmei; Li, Ping; Zhang, Jing; Xie, Li

    2016-09-01

    To evaluate the treatment efficacies and toxicities of concurrent cetuximab-based bioradiotherapy (BRT) or cisplatin-based chemoradiotherapy (CRT) in locally advanced nasopharyngeal carcinoma. :Patients with previously untreated locally advanced nasopharyngeal carcinoma were matched into pairs, and enrolled into the study. All patients were given either BRT or CRT. Survival outcomes, toxicities, and prognostic factors were evaluated. :A total of 112 patients were enrolled. The 5-year overall survival was 79.3% and 79.5% in CRT and BRT arm, respectively (P = 0.797) and the 5-year DFS was 73.5% and 74.6%, respectively (P = 0.953). In toxicity analysis, CRT arm had more significant decrease in white blood cell, platelet, hemoglobin, and severe vomiting, while more severe skin reactions and mucositis were shown in BRT arm. :BRT was not less efficacious than traditional CRT. They lead to different aspects of toxicities. If patients cannot stand more severe toxicities caused by CRT, BRT could be an ideal alternative. PMID:27684830

  4. In vivo Raman spectroscopy of human uterine cervix: exploring the utility of vagina as an internal control

    NASA Astrophysics Data System (ADS)

    Shaikh, Rubina; Dora, Tapas Kumar; Chopra, Supriya; Maheshwari, Amita; Kedar K., Deodhar; Bharat, Rekhi; Krishna, C. Murali

    2014-08-01

    In vivo Raman spectroscopy is being projected as a new, noninvasive method for cervical cancer diagnosis. In most of the reported studies, normal areas in the cancerous cervix were used as control. However, in the Indian subcontinent, the majority of cervical cancers are detected at advanced stages, leaving no normal sites for acquiring control spectra. Moreover, vagina and ectocervix are reported to have similar biochemical composition. Thus, in the present study, we have evaluated the feasibility of classifying normal and cancerous conditions in the Indian population and we have also explored the utility of the vagina as an internal control. A total of 228 normal and 181 tumor in vivo Raman spectra were acquired from 93 subjects under clinical supervision. The spectral features in normal conditions suggest the presence of collagen, while DNA and noncollagenous proteins were abundant in tumors. Principal-component linear discriminant analysis (PC-LDA) yielded 97% classification efficiency between normal and tumor groups. An analysis of a normal cervix and vaginal controls of cancerous and noncancerous subjects suggests similar spectral features between these groups. PC-LDA of tumor, normal cervix, and vaginal controls further support the utility of the vagina as an internal control. Overall, findings of the study corroborate with earlier studies and facilitate objective, noninvasive, and rapid Raman spectroscopic-based screening/diagnosis of cervical cancers.

  5. In vivo Raman spectroscopy of human uterine cervix: exploring the utility of vagina as an internal control.

    PubMed

    Shaikh, Rubina; Dora, Tapas Kumar; Chopra, Supriya; Maheshwari, Amita; Kedar K, Deodhar; Bharat, Rekhi; Krishna, C Murali

    2014-08-01

    In vivo Raman spectroscopy is being projected as a new, noninvasive method for cervical cancer diagnosis. In most of the reported studies, normal areas in the cancerous cervix were used as control. However, in the Indian subcontinent, the majority of cervical cancers are detected at advanced stages, leaving no normal sites for acquiring control spectra. Moreover, vagina and ectocervix are reported to have similar biochemical composition. Thus, in the present study, we have evaluated the feasibility of classifying normal and cancerous conditions in the Indian population and we have also explored the utility of the vagina as an internal control. A total of 228 normal and 181 tumor in vivo Raman spectra were acquired from 93 subjects under clinical supervision. The spectral features in normal conditions suggest the presence of collagen, while DNA and noncollagenous proteins were abundant in tumors. Principal-component linear discriminant analysis (PC-LDA) yielded 97% classification efficiency between normal and tumor groups. An analysis of a normal cervix and vaginal controls of cancerous and noncancerous subjects suggests similar spectral features between these groups. PC-LDA of tumor, normal cervix, and vaginal controls further support the utility of the vagina as an internal control. Overall, findings of the study corroborate with earlier studies and facilitate objective, noninvasive, and rapid Raman spectroscopic-based screening/diagnosis of cervical cancers.

  6. The mechanical role of the cervix in pregnancy

    PubMed Central

    Myers, Kristin M.; Feltovich, Helen; Mazza, Edoardo; Vink, Joy; Bajka, Michael; Wapner, Ronald J.; Hall, Timothy J.; House, Michael

    2015-01-01

    Appropriate mechanical function of the uterine cervix is critical for maintaining a pregnancy to term so that the fetus can develop fully. At the end of pregnancy, however, the cervix must allow delivery, which requires it to markedly soften, shorten and dilate. There are multiple pathways to spontaneous preterm birth, the leading global cause of death in children less than 5 years old, but all culminate in premature cervical change, because that is the last step in the final common pathway to delivery. The mechanisms underlying premature cervical change in pregnancy are poorly understood, and therefore current clinical protocols to assess preterm birth risk are limited to surrogate markers of mechanical function, such as sonographically measured cervical length. This is what motivates us to study the cervix, for which we propose investigating clinical cervical function in parallel with a quantitative engineering evaluation of its structural function. We aspire to develop a common translational language, as well as generate a rigorous integrated clinical-engineering framework for assessing cervical mechanical function at the cellular to organ level. In this review, we embark on that challenge by describing the current landscape of clinical, biochemical, and engineering concepts associated with the mechanical function of the cervix during pregnancy. Our goal is to use this common platform to inspire novel approaches to delineation of normal and abnormal cervical function in pregnancy. PMID:25841293

  7. The mechanical role of the cervix in pregnancy.

    PubMed

    Myers, Kristin M; Feltovich, Helen; Mazza, Edoardo; Vink, Joy; Bajka, Michael; Wapner, Ronald J; Hall, Timothy J; House, Michael

    2015-06-25

    Appropriate mechanical function of the uterine cervix is critical for maintaining a pregnancy to term so that the fetus can develop fully. At the end of pregnancy, however, the cervix must allow delivery, which requires it to markedly soften, shorten and dilate. There are multiple pathways to spontaneous preterm birth, the leading global cause of death in children less than 5 years old, but all culminate in premature cervical change, because that is the last step in the final common pathway to delivery. The mechanisms underlying premature cervical change in pregnancy are poorly understood, and therefore current clinical protocols to assess preterm birth risk are limited to surrogate markers of mechanical function, such as sonographically measured cervical length. This is what motivates us to study the cervix, for which we propose investigating clinical cervical function in parallel with a quantitative engineering evaluation of its structural function. We aspire to develop a common translational language, as well as generate a rigorous integrated clinical-engineering framework for assessing cervical mechanical function at the cellular to organ level. In this review, we embark on that challenge by describing the current landscape of clinical, biochemical, and engineering concepts associated with the mechanical function of the cervix during pregnancy. Our goal is to use this common platform to inspire novel approaches to delineate normal and abnormal cervical function in pregnancy. PMID:25841293

  8. The mechanical role of the cervix in pregnancy.

    PubMed

    Myers, Kristin M; Feltovich, Helen; Mazza, Edoardo; Vink, Joy; Bajka, Michael; Wapner, Ronald J; Hall, Timothy J; House, Michael

    2015-06-25

    Appropriate mechanical function of the uterine cervix is critical for maintaining a pregnancy to term so that the fetus can develop fully. At the end of pregnancy, however, the cervix must allow delivery, which requires it to markedly soften, shorten and dilate. There are multiple pathways to spontaneous preterm birth, the leading global cause of death in children less than 5 years old, but all culminate in premature cervical change, because that is the last step in the final common pathway to delivery. The mechanisms underlying premature cervical change in pregnancy are poorly understood, and therefore current clinical protocols to assess preterm birth risk are limited to surrogate markers of mechanical function, such as sonographically measured cervical length. This is what motivates us to study the cervix, for which we propose investigating clinical cervical function in parallel with a quantitative engineering evaluation of its structural function. We aspire to develop a common translational language, as well as generate a rigorous integrated clinical-engineering framework for assessing cervical mechanical function at the cellular to organ level. In this review, we embark on that challenge by describing the current landscape of clinical, biochemical, and engineering concepts associated with the mechanical function of the cervix during pregnancy. Our goal is to use this common platform to inspire novel approaches to delineate normal and abnormal cervical function in pregnancy.

  9. Small cell neuroendocrine carcinoma of the endometrium with pulmonary metastasis: A clinicopathologic study of a case and a brief review of the literature

    PubMed Central

    D'Antonio, Antonio; Addesso, Maria; Caleo, Alessia; Guida, Maurizio; Zeppa, Pio

    2015-01-01

    Neuroendocrine carcinomas (NEC) of the female genital tract are aggressive and rare tumors that usually involve the cervix and ovary, and are seen rarely in the endometrium in perimenopausal or postmenopausal women. We presented a case of a73 year-old postmenopausal woman with vaginal bleeding and abdominal pain. A subsequent computerized tomography (CT) scan of pelvis showed an enlarged uterus (20,0 × 12,0 cm) with para-aortic and pelvic lymph node metastases. She underwent surgical debulking and staging of an endometrial tumor with omental metastasis and positive lymph nodes. The pathological diagnosis was primary small cell carcinoma (SCC) combined with endometrioid carcinoma of uterine corpus. Her final FIGO stage was IVB. Three months after surgery CT-total body showed a metastasis to left lung of SCC. Because the small-cell component of endometrial tumor showed a strong positivity for TTF1 as pulmonary counterpart a differential diagnosis with a primary small cell carcinoma of the lung should be made. Identifying an appropriate therapeutic management for SCC of endometrium is challenging since these are extremely rare tumors. An optimal initial therapeutic approach to this rare disease, especially at an advanced stage, has not yet been clearly defined. However, in these a multidisciplinary therapy, including surgery, chemotherapy, and radiotherapy represent until this time the only therapeutic option. PMID:26900464

  10. Clinical Tumor Dimensions May Be Useful to Prevent Geographic Miss in Conventional Radiotherapy of Uterine Cervix Cancer-A Magnetic Resonance Imaging-Based Study

    SciTech Connect

    Justino, Pitagoras Baskara; Baroni, Ronaldo; Blasbalg, Roberto; Andrade Carvalho, Heloisa de

    2009-06-01

    Purpose: To evaluate the risk of geographic miss associated with the classic four-field 'box' irradiation technique and to define the variables that predict this risk. Materials and Methods: The study population consisted of 80 patients with uterine cervix cancer seen between 2001 and 2006. Median age was 55 years (23-82 years), and 72 (90%) presented with squamous cell carcinoma. Most patients (68.7%) presented with locally advanced disease (IIb or more). Magnetic resonance imaging findings from before treatment were compared with findings from simulation of the conventional four-field 'box' technique done with rectal contrast. Study variables included tumor volume; involvement of vagina, parametrium, bladder, or rectum; posterior displacement of the anterior rectal wall; and tumor anteroposterior diameter (APD). Margins were considered adequate when the target volume (primary tumor extension, whole uterine body, and parametrium) was included within the field limits and were at least 1 cm in width. Results: Field limits were inadequate in 45 (56%) patients: 29 (36%) patients at the anterior and 28 (35%) at the posterior border of the lateral fields. Of these, 12 patients had both anterior and posterior miss, and this risk was observed in all stages of the disease (p = 0.076). Posterior displacement of the anterior rectal wall beyond S2-S3 was significantly correlated with the risk of geographic miss (p = 0.043). Larger tumors (APD 6 cm or above and volume above 50 cm{sup 3}) were also significantly correlated with this risk (p = 0.004 and p = 0.046, respectively). Conclusions: Posterior displacement of the anterior rectal wall, tumor APD, and volume can be used as guidance in evaluating the risk of geographic miss.

  11. Solitary fibrous tumor of the uterine cervix.

    PubMed

    Rahimi, Kurosh; Shaw, Patricia A; Chetty, Runjan

    2010-03-01

    A 68-year-old woman with stage pT1b1 N0 cervical squamous carcinoma had an incidental cervical polyp. The polyp measured 1.7 cm in maximal diameter and histologic evaluation showed it to be composed of spindle-shaped cells with hypercellular and hypocellular foci. The stroma was collagenized and contained several dilated vascular channels that imparted a hemangiopericytic pattern to the lesion. Immunohistochemistry showed the spindle cells to be positive for vimentin, CD99, CD34, bcl-2, ER, PR, and beta-catenin (cytoplasmic) but negative for EMA, S100, factor XIIIa, AE1/AE3, caldesmon, desmin, CD31, and smooth muscle actin. The morphology and immunophenotype was in keeping with a diagnosis of a solitary fibrous tumor (SFT). SFT shares several histologic features of a superficial cervicovaginal myofibroblastoma; the cellular variability, pattern and distribution of vessels, stromal collagenization, and desmin negativity favors SFT.

  12. Ectopic decidua and metastatic squamous carcinoma: presentation in a single pelvic lymph node.

    PubMed

    Cobb, C J

    1988-06-01

    The presence of ectopic decidua in pelvic lymph nodes from patients with squamous carcinoma of the cervix makes evaluation for metastatic disease difficult due to the light microscopic similarity between decidua and sheets of squamous epithelial cells. A patient is present in whom decidualized endometriosis was intimately associated with metastatic moderately differentiate squamous carcinoma in a single pelvic lymph node. This phenomenon afforded an excellent opportunity to study the unique morphologic features that distinguish these two entities. A prior report of this kind was not found. In the absence of obvious squamous differentiation (i.e., intercellular bridges, dyskeratosis, and keratin "pearl" formation), as is frequently the case with squamous carcinoma of the cervix, the light microscopic features that are most useful in distinguishing squamous carcinoma from decidua include the presence of well-defined nests of cohesive cells, nuclear hyperchromasia, and cellular pleomorphism.

  13. Bortezomib Followed by the Addition of Doxorubicin at Disease Progression in Treating Patients With Locally Advanced, Recurrent, or Metastatic Adenoid Cystic Carcinoma (Cancer) of the Head and Neck

    ClinicalTrials.gov

    2013-01-23

    Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Salivary Gland Cancer; Salivary Gland Adenoid Cystic Carcinoma; Stage III Adenoid Cystic Carcinoma of the Oral Cavity; Stage III Salivary Gland Cancer; Stage IV Adenoid Cystic Carcinoma of the Oral Cavity; Stage IV Salivary Gland Cancer

  14. [Results of complex treatment of patients with squamous cell carcinoma of the anal canal using advanced radiotherapy technologies].

    PubMed

    Glebovskaya, V V; Tkachev, S I; Rasulov, A O; Tsaryuk, V F; Gordeev, S S; Fedyanin, M Yu; Aliev, V A; Mamedly, Z Z; Kuzmichev, D V; Trofimova, O P; Borisova, T N; Yazhgunovich, I P

    2015-01-01

    During recent decades radiotherapy is the basis, on which it is built a medical complex that is the first-line treatment of patients with squamous cell carcinoma of the anal canal. An increase of overall and disease-free survival and quality of life of patients with squamous cell carcinoma of the anal canal at the present stage of development of a comprehensive medical treatment is largely due to the improvement of technical equipment of radiotherapy departments of oncology clinics. The use of modem linear electron accelerators and systems of computer dosimetric planning to create a 3D program of isodose distribution, diagnostic devices (computed tomography and magnetic resonance imaging) as well as a number of other conditions permit accurate summarizing of proposed dose, reducing of absorbed dose to critical structures, diminishing unplanned interruptions in chemoradiotherapy course by means of modern technologies of conformal radiotherapy (3D CRT, IMRT, VMAT). The paper presents the preliminary results of a comprehensive medical treatment of 14 patients with squamous cell carcinoma of the anal canal. PMID:26571840

  15. HPV16 synthetic long peptide (HPV16-SLP) vaccination therapy of patients with advanced or recurrent HPV16-induced gynecological carcinoma, a phase II trial

    PubMed Central

    2013-01-01

    Background Human papilloma virus type 16 (HPV16)-induced gynecological cancers, in particular cervical cancers, are found in many women worldwide. The HPV16 encoded oncoproteins E6 and E7 are tumor-specific targets for the adaptive immune system permitting the development of an HPV16-synthetic long peptide (SLP) vaccine with an excellent treatment profile in animal models. Here, we determined the toxicity, safety, immunogenicity and efficacy of the HPV16 SLP vaccine in patients with advanced or recurrent HPV16-induced gynecological carcinoma. Methods Patients with HPV16-positive advanced or recurrent gynecological carcinoma (n = 20) were subcutaneously vaccinated with an HPV16-SLP vaccine consisting of a mix of 13 HPV16 E6 and HPV16 E7 overlapping long peptides in Montanide ISA-51 adjuvant. The primary endpoints were safety, toxicity and tumor regression as determined by RECIST. In addition, the vaccine-induced T-cell response was assessed by proliferation and associated cytokine production as well as IFNγ-ELISPOT. Results No systemic toxicity beyond CTCAE grade II was observed. In a few patients transient flu-like symptoms were observed. In 9 out of 16 tested patients vaccine-induced HPV16-specific proliferative responses were detected which were associated with the production of IFNγ, TNFα, IL-5 and/or IL-10. ELISPOT analysis revealed a vaccine-induced immune response in 11 of the 13 tested patients. The capacity to respond to the vaccine was positively correlated to the patient’s immune status as reflected by their response to common recall antigens at the start of the trial. Median survival was 12.6 ± 9.1 months. No regression of tumors was observed among the 12 evaluable patients. Nineteen patients died of progressive disease. Conclusions The HPV16-SLP vaccine was well tolerated and induced a broad IFNγ-associated T-cell response in patients with advanced or recurrent HPV16-induced gynecological carcinoma but neither induced tumor regression nor

  16. Clinical value of routine serum squamous cell carcinoma antigen in follow-up of patients with locally advanced cervical cancer treated with radiation or chemoradiation

    PubMed Central

    Oh, Jinju; Lee, Hyun Joo; Lee, Tae Sung; Kim, Ju Hyun; Koh, Suk Bong

    2016-01-01

    Objective The objective of this study was to evaluate the clinical benefits of routine squamous cell carcinoma antigen (SCC-Ag) monitoring of patients with locally advanced cervical squamous cell carcinoma treated with radiation or chemoradiation. Methods A total of 53 patients with recurrent cervical squamous cell carcinoma treated with radiotherapy or chemoradiation were enrolled in this study. A retrospective review of medical records was conducted. The role of routine monitoring of serum SCC-Ag was evaluated in terms of cost effectiveness and effect on survival after diagnosis of recurrence. Results Serum SCC-Ag abnormality (≥2.5 ng/mL) was observed in 62.3% of patients when recurrent disease was diagnosed. The first indicator of relapse was abnormal serum SCC-Ag level in 21 patients (39.6%), 10 of whom had asymptomatic recurrent disease amenable to salvage therapy. Adding SCC-Ag measurement to the basic follow up protocol improved the sensitivity for detecting recurrence (The sensitivity of the basic protocol vs. addition of SCC-Ag: 49.1% vs. 88.7%, P<0.001). Twenty-three patients who were candidates for salvage therapy with curative intent showed better survival compared with those who were not candidates for therapy (5-year survival: 36.6% vs. 0%, P=0.012). Conclusion Surveillance with routine serum SCC-Ag monitoring can better detect asymptomatic recurrent disease that is potentially amenable to salvage therapy with curative intent. Early diagnosis of recurrent disease that can be treated with salvage therapy may lead to better survival. PMID:27462593

  17. Implementation of image-guided brachytherapy (IGBT) for patients with uterine cervix cancer: a tumor volume kinetics approach

    PubMed Central

    Mendez, Lucas Castro; Stuart, Silvia Radwanski; Guimarães, Roger Guilherme Rodrigues; Ramos, Clarissa Cerchi Angotti; de Paula, Lucas Assad; de Sales, Camila Pessoa; Chen, André Tsin Chih; Blasbalg, Roberto; Baroni, Ronaldo Hueb

    2016-01-01

    Purpose To evaluate tumor shrinking kinetics in order to implement image-guided brachytherapy (IGBT) for the treatment of patients with cervix cancer. Material and methods This study has prospectively evaluated tumor shrinking kinetics of thirteen patients with uterine cervix cancer treated with combined chemoradiation. Four high dose rate brachytherapy fractions were delivered during the course of pelvic external beam radiation therapy (EBRT). Magnetic resonance imaging (MRI) exams were acquired at diagnosis (D), first (B1), and third (B3) brachytherapy fractions. Target volumes (GTV and HR-CTV) were calculated by both the ellipsoid formula (VE) and MRI contouring (VC), which were defined by a consensus between at least two radiation oncologists and a pelvic expert radiologist. Results Most enrolled patients had squamous cell carcinoma and FIGO stage IIB disease, and initiated brachytherapy after the third week of pelvic external beam radiation. Gross tumor volume volume reduction from diagnostic MRI to B1 represented 61.9% and 75.2% of the initial volume, when measured by VE and VC, respectively. Only a modest volume reduction (15-20%) was observed from B1 to B3. Conclusions The most expressive tumor shrinking occurred in the first three weeks of oncological treatment and was in accordance with gynecological examination. These findings may help in IGBT implementation. PMID:27648083

  18. Implementation of image-guided brachytherapy (IGBT) for patients with uterine cervix cancer: a tumor volume kinetics approach

    PubMed Central

    Mendez, Lucas Castro; Stuart, Silvia Radwanski; Guimarães, Roger Guilherme Rodrigues; Ramos, Clarissa Cerchi Angotti; de Paula, Lucas Assad; de Sales, Camila Pessoa; Chen, André Tsin Chih; Blasbalg, Roberto; Baroni, Ronaldo Hueb

    2016-01-01

    Purpose To evaluate tumor shrinking kinetics in order to implement image-guided brachytherapy (IGBT) for the treatment of patients with cervix cancer. Material and methods This study has prospectively evaluated tumor shrinking kinetics of thirteen patients with uterine cervix cancer treated with combined chemoradiation. Four high dose rate brachytherapy fractions were delivered during the course of pelvic external beam radiation therapy (EBRT). Magnetic resonance imaging (MRI) exams were acquired at diagnosis (D), first (B1), and third (B3) brachytherapy fractions. Target volumes (GTV and HR-CTV) were calculated by both the ellipsoid formula (VE) and MRI contouring (VC), which were defined by a consensus between at least two radiation oncologists and a pelvic expert radiologist. Results Most enrolled patients had squamous cell carcinoma and FIGO stage IIB disease, and initiated brachytherapy after the third week of pelvic external beam radiation. Gross tumor volume volume reduction from diagnostic MRI to B1 represented 61.9% and 75.2% of the initial volume, when measured by VE and VC, respectively. Only a modest volume reduction (15-20%) was observed from B1 to B3. Conclusions The most expressive tumor shrinking occurred in the first three weeks of oncological treatment and was in accordance with gynecological examination. These findings may help in IGBT implementation.

  19. Parenteral Nutrition for Patients Treated for Locally Advanced Inoperable Tumors of the Head and Neck

    ClinicalTrials.gov

    2016-08-10

    Squamous Cell Carcinoma of the Hypopharynx Stage III; Squamous Cell Carcinoma of the Hypopharynx Stage IV; Laryngeal Squamous Cell Carcinoma Stage III; Laryngeal Squamous Cell Carcinoma Stage IV; Oropharyngeal Squamous Cell Carcinoma Stage III; Oropharyngeal Squamous Cell Carcinoma Stage IV; Squamous Cell Carcinoma of the Oral Cavity Stage III; Squamous Cell Carcinoma of the Oral Cavity Stage IV; Locally Advanced Malignant Neoplasm

  20. Long-term follow-up after transoral laser microsurgery and adjuvant radiotherapy for advanced recurrent squamous cell carcinoma of the head and neck

    SciTech Connect

    Christiansen, Hans . E-mail: hchrist@gwdg.de; Hermann, Robert Michael; Martin, Alexios; Florez, Rodrigo; Kahler, Elke; Nitsche, Mirko; Hille, Andrea; Steiner, Wolfgang; Hess, Clemens F.; Pradier, Olivier

    2006-07-15

    Purpose: The aim of this study was to evaluate the efficacy of adjuvant radiotherapy after transoral laser microsurgery for advanced recurrent head-and-neck squamous cell carcinoma (HNSCC). Patients and Methods: Between 1988 and 2000, 37 patients with advanced local recurrences (23 local and 14 locoregional recurrences) of HNSCC without distant metastases were treated in curative intent with organ-preserving transoral laser microsurgery and adjuvant radiotherapy (before 1994 split-course radiotherapy with carboplatinum, after 1994 conventional radiotherapy). Initial therapy of the primary (8.1% oral cavity, 35.1% oropharynx, 13.5% hypopharynx, and 43.3% larynx) before relapse was organ-preserving transoral laser microsurgery without any adjuvant therapy. Results: After a median follow-up of 124 months, the 5-year overall survival rate was 21.3%, the loco-regional control rate 48.3%, respectively. In multivariate analysis, stage of original primary tumor (Stage I/II vs. Stage III/IV), and patient age (<58 years vs. {>=}58 years) showed statistically significant impact on prognosis. In laryngeal cancer, larynx preservation rate after treatment for recurrent tumor was 50% during follow-up. Conclusion: Our data show that organ-preserving transoral laser microsurgery followed by adjuvant radiotherapy is a curative option for patients who have advanced recurrence after transoral laser surgery and is an alternative to radical treatment.

  1. Adrenocortical carcinoma.

    PubMed

    Baudin, Eric

    2015-06-01

    Recent developments in the treatment of adrenocortical carcinoma (ACC) include diagnostic and prognostic risk stratification algorithms, increasing evidence of the impact of historical therapies on overall survival, and emerging targets from integrated epigenomic and genomic analyses. Advances include proper clinical and molecular characterization of all patients with ACC, standardization of proliferative index analyses, referral of these patients to large cancer referral centers at the time of first surgery, and development of new trials in patients with well-characterized ACC. Networking and progress in the molecular characterization of ACC constitute the basis for significant future therapeutic breakthroughs. PMID:26038209

  2. Therapeutic uterine-cervix cancer vaccines in humans.

    PubMed

    Gariglio, P; Benitez-Bribiesca, L; Berumen, J; Alcocer, J M; Tamez, R; Madrid, V

    1998-01-01

    Infection with high-risk human papillomavirus (HPV) types is involved in early stages of uterine=cervix cancer development. The virally encoded E6 and E7 oncoproteins behave as tumor-specific antigens and represent targets for a vaccine designed to control HPV-induced tumors. Using either proteins or peptides based on E6 and E7 oncoproteins of HPV16 and 18, phase I clinical trials of therapeutic vaccines against HPV-associated cervical cancers have recently been reported. Although the effectiveness of these vaccines cannot be evaluated in such small studies, they constitute an important step toward the development of therapeutic uterine=cervix cancer vaccines. A polytope DNA vaccination approach combined with immunomodulatory cytokines may offer an excellent strategy to reduce the risk of relapse and metastasis following conventional therapies. PMID:9887543

  3. Injuries to the cervix in sexual assault victims.

    PubMed

    Keller, Patricia; Lechner, Megan

    2010-01-01

    Little research has addressed the types and meaning of genital injury in sexual assault victims. An even smaller amount of research exists documenting injury to the cervix in sexual assault victims. The purpose of this study was to examine the frequency of cervical injuries in women following sexual assault, the types of injuries seen, the mechanisms that are related to the injuries, and the types of injuries related to each mechanism. A retrospective chart review was conducted. A total of 538 charts were examined, with a final sample size of 114. Within this sample, 87.8% (n= 100) presented with no injury to the cervix, and 12.3% (n= 14) had documented injury. All statistical analyses were nonsignificant; however, clinical implications are noted. Recommendations for future research are made.

  4. Communicating septate uterus with double cervix: a rare malformation.

    PubMed

    Lev-Toaff, A S; Kim, S S; Toaff, M E

    1992-05-01

    The class of uterine malformations known as communicating uteri is characterized by two separate uterocervical cavities connected by an isthmic communication. Nine types have been described. We report the second proven case of a septate communicating uterus with double cervix. Investigation of secondary infertility in a woman with a history of second-trimester spontaneous abortion revealed two cervices on a speculum examination. A work-up for uterine anomaly began with endovaginal sonography, which demonstrated a normal fundal contour. A septum symmetrically dividing the endometrial cavity and two cervical canals were seen. The separated endometrial echoes converged at the isthmus, indicating a communicating uterus. Hysterosalpingography confirmed the diagnosis; injection of each cervix resulted in opacification of both hemicavities via the isthmic defect. Laparoscopy confirmed the normal fundal contour. It is believed that the etiology of this malformation involves failure of fusion of the distal müllerian ducts and arrested septal resorption above the isthmus.

  5. Matched Survival Analysis in Patients With Locoregionally Advanced Resectable Oropharyngeal Carcinoma: Platinum-Based Induction and Concurrent Chemoradiotherapy Versus Primary Surgical Resection

    SciTech Connect

    Boscolo-Rizzo, Paolo; Gava, Alessandro; Baggio, Vittorio; Marchiori, Carlo; Stellin, Marco; Fuson, Roberto; Lamon, Stefano; Da Mosto, Maria Cristina

    2011-05-01

    Purpose: The outcome of a prospective case series of 47 patients with newly diagnosed resectable locoregionally advanced oropharyngeal squamous cell carcinoma treated with platinum-based induction-concurrent chemoradiotherapy (IC/CCRT) was compared with the outcome of 47 matched historical control patients treated with surgery and postoperative RT. Methods and Materials: A total of 47 control patients with locoregionally advanced oropharyngeal squamous cell carcinoma were identified from review of a prospectively compiled comprehensive computerized head-and-neck cancer database and were matched with a prospective case series of patients undergoing IC/CCRT by disease stage, nodal status, gender, and age ({+-}5 years). The IC/CCRT regimen consisted of one cycle of induction chemotherapy followed by conventionally fractionated RT to a total dose of 66-70 Gy concomitantly with two cycles of chemotherapy. Each cycle of chemotherapy consisted of cisplatinum, 100 mg/m{sup 2}, and a continuous infusion of 5-fluorouracil, 1,000 mg/m{sup 2}/d for 5 days. The survival analysis was performed using Kaplan-Meier estimates. Matched-pair survival was compared using the Cox proportional hazards model. Results: No significant difference was found in the overall survival or progression-free survival rates between the two groups. The matched analysis of survival did not show a statistically significant greater hazard ratio for overall death (hazard ratio, 1.35; 95% confidence interval, 0.65-2.80; p = .415) or progression (hazard ratio, 1.44; 95% confidence interval, 0.72-2.87; p = .301) for patients undergoing IC/CCRT. Conclusion: Although the sample size was small and not randomized, this matched-pair comparison between a prospective case series and a historical cohort treated at the same institution showed that the efficacy of IC/CCRT with salvage surgery is as good as primary surgical resection and postoperative RT.

  6. Phase II trial of fluorouracil and recombinant interferon alfa-2a in patients with advanced colorectal carcinoma: an Eastern Cooperative Oncology Group study.

    PubMed

    Wadler, S; Lembersky, B; Atkins, M; Kirkwood, J; Petrelli, N

    1991-10-01

    In a pilot clinical trial, treatment of patients with advanced colorectal carcinoma with the combination of fluorouracil (5FU) and recombinant interferon alfa-2a (IFN) resulted in objective tumor regression in 62% of patients. To confirm these findings in a multiinstitutional setting, a phase II clinical trial was initiated by the Eastern Cooperative Oncology Group (ECOG) in 1989. The treatment regimen was identical to that used in the earlier study: 5FU 750 mg/m2/d for 5 days as a continuous infusion followed by weekly outpatient bolus therapy and IFN 9MU subcutaneously beginning day 1 and administered three times per week. Doses were modified for gastrointestinal, hematologic, and neurologic toxicity and for fatigue, similarly to those used in the previous pilot trial. Thirty-eight patients were registered; 36 are evaluable for response (one lost to follow-up and one with nonmeasurable disease). All patients had metastatic or locally recurrent disease beyond the scope of resection; 31 of 38 had liver metastases, and 20 of 38 had two or more sites of involvement. Eight patients had grade 4 toxicities, including sepsis (nonneutropenic) (one), watery diarrhea (two), and granulocytopenia (six). Grade 3 neurologic toxicities were observed in two (5%) patients and included slurred speech and gait disturbance. Objective response was 42% (95% confidence interval [Cl], 27% to 58%), including one clinical complete responder and 14 partial responders. Among the responding patients, the median time to treatment failure was 8 months. Two patients remain on treatment at 10+ and 16+ months: median survival has not been reached. The results of this multiinstitutional trial suggest that the addition of IFN to 5FU enhances the objective response rates achieved in patients with advanced colorectal carcinoma and that the toxicities of this regimen are acceptable. PMID:1919631

  7. [Mechanism of the cancerogenesis in cervix paraepidermal epithelium cells with chronic infection of oncogenic types of human papiloma virus].

    PubMed

    Kedzia, Witold; Goździcka-Józefiak, Anna

    2007-09-01

    The human papillomavirus family is composed of a large number of different and variably related types, each of which is associated with a characteristic set of epithelial lesions. Each of the many identified types of human papillomavirus have shown considerable specificity of different anatomical sites and different characteristic lesions. HPV 6 and 11 are frequently associated with benign condylomas, while HPV 16 and 18 are associated with malignant progression and cervical cancer. The genome of papillomaviruses is composed of a circular double stranded DNA. Various open reading frames (ORFs) are located on only one DNA strand. The coding strand contains from 8 to 10 translational ORFs. Among them, only 6 to 8 were designated as early and 2 as late. The role of HPVs 16 and 18 in uterine cervix carcinoma has been well-documented, but their contriobution to carcinogenesis of other neoplasias is still questionable.

  8. Applicator modeling for electromagnetic thermotherapy of cervix cancer.

    PubMed

    Rezaeealam, Behrooz

    2015-03-01

    This report proposes an induction heating coil design that can be used for producing strong magnetic fields around ferromagnetic implants located in the cervix of uterus. The effect of coil design on the uniformity and extent of heat generation ability is inspected. Also, a numerical model of the applicator is developed that includes the ferromagnetic implants, and is coupled to the bioheat transfer model of the body tissue. Then, the ability of the proposed applicator for electromagnetic thermotherapy is investigated.

  9. Conservative treatment of coexisting microinvasive squamous and adenocarcinoma of the cervix: report of two cases and literature review

    PubMed Central

    Sopracordevole, Francesco; Di Giuseppe, Jacopo; Cervo, Silvia; Buttignol, Monica; Giorda, Giorgio; Ciavattini, Andrea; Canzonieri, Vincenzo

    2016-01-01

    Coexistence of microinvasive squamous cell carcinoma (MISCC) and microinvasive adenocarcinoma (MIAC) of the cervix is a rare phenomenon with very few clinically significant cases described in the literature. While a conservative approach has been studied, and may be effective in MISCC, a lower number of studies that recommend conservative treatment are available for MIAC. We report two cases of synchronous cervix lesions in two separate foci, MISCC and MIAC, who underwent fertility-sparing treatment with long-term follow-up. We describe clinical, histological, and immunohistochemical features of the two cases. The first case is a 41-year-old female with a diagnosis of MIAC of endocervical type, grade 1 differentiation, with a stromal invasion, associated with a separate area of squamous cell carcinoma (International Federation of Gynecology and Obstetrics/TNM stage: pT1a1G1). The second case is a 45-year-old female with a diagnosis of plurifocal MISCC, associated with an MIAC of endocervical type with a stromal invasion (International Federation of Gynecology and Obstetrics/TNM stage: pT1a1G1). After multidisciplinary counseling, both patients accepted conization as definitive treatment. Eleven years after the conization, all tests (Papanicolaou smear, colposcopy, cervical curettage, and hybrid capture 2-human papillomavirus test) planned quarterly in the first year and every 6 months in the subsequent years were negative in both patients. In women affected by stage IA1 squamous cervical cancer coexisting with stage IA1 adenocarcinoma endocervical type, with clear margins, and without lymphovascular space invasion, cervical conization may be considered a fertility-preserving, safe, and definitive therapeutic option. PMID:26869798

  10. Treatment of advanced or recurrent endometrial carcinoma with combination of etoposide, cisplatin, and 5-fluorouracil: a phase II study.

    PubMed

    Pierga, J Y; Dieras, V; Paraiso, D; Dorval, T; Palangie, T; Beuzeboc, P; Jouve, M; Scholl, S M; Garcia-Giralt, E; Pouillart, P

    1996-01-01

    Forty-nine consecutive patients with metastatic or recurrent endometrial carcinoma were treated with a monthly combination chemotherapy consisting of VP 16-213 80 mg/m2 i.v. Days 1-3, 5-fluorouracil (5-FU) 600 mg/m2 i.v. Days 1-3, and cisplatin 35 mg/m2 i.v. Days 1-3. The objective response rate was 41% (95% CI, 27-54%) with 14.3% complete responses. The median survival duration was 14 months. The median response duration was 12 months. The estimated median survival for responders was 20 months. Three patients are still free of disease 5 years after treatment. The major toxic effects were myelosuppression (less than 25% of grade III and IV leucopenia, and 14% grade III and IV thrombocytopenia). Grade III peripheral neuropathy was observed in five patients. Cisplatin administration had to be stopped due to renal toxicity in six patients. No treatment-related deaths occurred. The combination of etoposide, 5 fluorouracil, and cisplatin is an effective regimen with an acceptable toxicity in patients with recurrent or metastatic endometrial carcinoma.

  11. Maintenance monotherapy with Gemcitabine following cisplatin-based primary combination chemotherapy in surgically treated advanced urothelial carcinoma: A matched-pair single institution analysis

    PubMed Central

    KALOGIROU, CHARIS; SVISTUNOV, ANDREY; KREBS, MARKUS; LAUSENMEYER, EVA MARIA; VERGHO, DANIEL; RIEDMILLER, HUBERTUS; KOCOT, ARKADIUS

    2016-01-01

    The role of maintenance therapy with Gemcitabine (GEM) following cisplatin-based combination chemotherapy (CBCC) in patients with surgically treated advanced urothelial carcinoma (UC) remains to be fully elucidated. In the present case control study, a retrospective analysis was performed to evaluate the role of GEM monotherapy following surgical intervention for advanced UC. Between 1999 and 2013, 38 patients were identified with surgically treated advanced UC after having completed CBCC, who were additionally treated quarterly with two consecutive GEM (1,250 mg/m2) infusions as maintenance therapy. This collective was matched by propensity score matching to a control collective (n=38) that received primary CBCC alone, and the overall survival (OS), cancer-specific survival (CSS) and progression-free survival (PFS) rates were determined for the two collectives using Kaplan-Meier estimates and the log-rank test. Regression analysis was performed using the Cox proportional hazards model. The median follow-up time was 37 months (interquartile range: 9–148). Interestingly, patients treated with GEM following primary chemotherapy had a significantly improved outcome with respect to the 5-year OS (46.2 vs. 26.4%, P=0.0314) and 5-year CSS (61.3 vs. 33.4%, P=0.0386) rates. Notably, the 5-year PFS rate did not differ between the two groups (10.3 vs. 16.1%, P=0.134). It is proposed that additional GEM maintenance monotherapy is able to improve survival rates following primary CBCC in surgically treated patients with advanced UC, suggesting a possible treatment option for patients with, e.g., unclear disease status, or those who would require an active maintenance therapy in the future. Prospective studies should further determine the impact of GEM monotherapy with respect to PFS rates in groups comprising larger numbers of patients. PMID:27073682

  12. [Advances in the research of BRAF(V600E) gene mutation correlated with papillary thyroid carcinoma].

    PubMed

    Xu, X Q; Wang, X H; Jing, J X

    2016-08-01

    The increase in the incidence of papillary thyroid carcinoma (PTC) is a serious threat to public health. V-raf murine sarcoma viral oncogene homolog B(BRAF)(V600E) gene mutation is not only the common genetics factors, but also is the early event in process of thyroid carcinogenesis. We mainly illustrate the mechanism of BRAF(V600E) gene in genesis and development of PTC and the correlation of BRAF(V600E) gene mutation and the clinicopathological characteristics of PTC. Finally, we briefly summarize some scientific achievements about tyrosine kinase inhibitors targeted for BRAF(V600E) gene and their clinical prospect in terms of translation medicine concept. In summary, BRAF(V600E) gene is expected to be a new molecular marker of PTC, which will take a new hope for individualized precise treatment for patients with PTC. PMID:27625138

  13. Cabozantinib in the treatment of advanced renal cell carcinoma: design, development, and potential place in the therapy

    PubMed Central

    Grassi, Paolo; Verzoni, Elena; Ratta, Raffaele; Mennitto, Alessia; de Braud, Filippo; Procopio, Giuseppe

    2016-01-01

    The treatment of metastatic renal cell carcinoma (mRCC) has markedly improved over the last few years with the introduction of several targeted agents in clinical practice. Nevertheless, either primary or secondary resistance to inhibition of VEGF and mTOR pathways has limited the clinical benefit of these systemic treatments. Recently, a better understanding of the involvement of MET and its ligand HGF in many biological processes made this signaling pathway an attractive therapeutic target in oncology, particularly in mRCC. Herein, we review the development of cabozantinib, a recently approved inhibitor of multiple tyrosine kinase receptors, including MET, VEGFRs, and AXL, which has proven to increase progression-free survival and overall survival when compared to everolimus in mRCC patients who had progressed after VEGFR-targeted therapy. Finally, we discuss the potential role of cabozantinib within the current treatment landscape for mRCC. PMID:27462141

  14. Comparison between nedaplatin and cisplatin plus docetaxel combined with intensity-modulated radiotherapy for locoregionally advanced nasopharyngeal carcinoma: a multicenter randomized phase II clinical trial

    PubMed Central

    Tang, Chunyuan; Wu, Fang; Wang, Rensheng; Lu, Heming; Li, Guisheng; Liu, Meilian; Zhu, Haisheng; Zhu, Jinxian; Zhang, Yong; Hu, Kai

    2016-01-01

    Nasopharyngeal carcinoma (NPC) is highly incident in southern China. Metastasis is the major cause of death in NPC patients. Concurrent chemoradiotherapy (CCRT) has been accepted as standard in the treatment of patients with locoregionally advanced nasopharyngeal carcinoma (NPC). However, induction chemotherapy (IC) also has benefits in this disease, especially in the patients with certain high-risk factors such as bulky and/or extensive nodal disease. It has been presented that adding IC to CCRT might be a reasonable approach and need more work to confirm. The optimal chemotherapeutic regimen combined with radiotherapy has not been determined so far. It is important to explore high effective and low toxic chemotherapy for the patients. In the multicenter prospective study, 223 patients with locoregionally advanced untreated NPC were randomized into experimental group and control group. The patients received two cycles of induction chemotherapy (IC) with docetaxel (DOC) plus nedaplatin (NDP) in experimental group every 3 weeks, followed by IMRT concurrent with weekly NDP for six cycles, and NDP was replaced by cisplatin (CDDP) in control group. More patients in experimental group could receive full courses of IC and concurrent chemoradiotherapy (CCRT) (P=0.013). There was no significant difference between the two groups in the percentage of reduction of GTVnx and GTVnd after IC (P=0.207 and P=0.107) and CR rate three months after completion of chemoradiotherapy (P=0.565 and P=0.738). With a mean follow-up of 35.1 months, no statistically significant difference in the 3-year OS, LRFS, RRFS, DMFS, and PFS was found. During IC, more patients suffered vomiting in control group (P=0.001). During CCRT, grade 3/4 neutropenia/thrombocytopenia were more common in experimental group (P=0.028 and P=0.035); whereas, severe anemia and vomiting were more common in control group (P=0.0001 and P=0.023). In conclusions, patients with locoregionally advanced NPC showed good

  15. CT-Based Evaluation of Tumor Volume After Intra-Arterial Chemotherapy of Locally Advanced Carcinoma of the Oral Cavity: Comparison with Clinical Remission Rates

    SciTech Connect

    Rohde, Stefan Turowski, Bernd; Berkefeld, Joachim; Kovacs, Adorjan F.

    2007-02-15

    Purpose. To assess the volume of locally advanced tumors of the oral cavity and the oropharynx before and after intra-arterial (i.a.) chemotherapy by means of computed tomography and to compare these data with clinically determined treatment response of the same patient population. Methods. Eighty-eight patients with histologically proven, advanced carcinoma of the oral cavity and/or the oropharynx (local tumor stages T3/4) received neoadjuvant i.a. chemotherapy with cisplatin as part of a multimodal therapeutic regimen, comprising (1) local chemotherapy, (2) surgery, and (3) combined radio-chemotherapy. Three weeks after the intervention, residual disease was evaluated radiologically by measurement of the tumor volume and clinically by inspection and palpation of the primary tumor according to WHO criteria. Results. Comparison of treatment response according to radiological and clinical criteria respectively revealed complete remission in 5% vs. 8% (p < 0.05), partial remission in 30% vs. 31%, stable disease in 61% vs. 58%, and tumor progression in 5% vs. 2%. Conclusion. Radiological volumetry and clinical evaluation found comparable response rates after local chemotherapy. However, in patients with good response after local treatment, volumetric measurement with CT may help to distinguish between partial and complete remission. Thus, radiological tumor volumetry provides precise and differentiated information about tumor response and should be used as an additional tool in treatment monitoring after local chemotherapy.

  16. A Multi-institutional Investigation of the Prognostic Value of Lymph Nodal Yield in Advanced Stage Oral Cavity Squamous Cell Carcinoma (OCSCC)

    PubMed Central

    Jaber, James J.; Zender, Chad A.; Mehta, Vikas; Davis, Kara; Ferris, Robert L.; Lavertu, Pierre; Rezaee, Rod; Feustel, Paul J.

    2014-01-01

    Background Although existing literature provides surgical recommendations for treating occult disease (cN0) in early stage oral cavity squamous cell carcinoma, a focus on late stage OCSCC is less pervasive. Methods The records of 162 late stage OCSCC pN0 individuals that underwent primary neck dissections were reviewed. Lymph node yield (LNY) as a prognosticator was examined. Results Despite being staged pN0, patients that had a higher LNY had an improved regional/distant control rates, DFS, DSS, and OS. LNY consistently outperformed all other standard variables as being the single best prognostic factor with a tight risk ratio range (RR = 0.95–0.98) even when correcting for the number of lymph nodes examined. Conclusion The results of this study showed that lower regional recurrence rates and improved survival outcomes were seen as lymph node yield increased for advanced T-stage OCSCC pN0. This suggests that increasing lymph node yield with an extended cervical lymphadenectomy may result in lower recurrence rates and improved survival outcomes for this advanced stage group. PMID:24038739

  17. Electrochemotherapy in combination with chemoradiotherapy in the treatment of oral carcinomas in advanced stages of disease: efficacy, safety, and clinical outcomes in a small number of selected cases

    PubMed Central

    Domanico, Rossana; Trapasso, Serena; Santoro, Mariaquila; Pingitore, Domenico; Allegra, Eugenia

    2015-01-01

    Introduction Electrochemotherapy (ECT) is a new therapeutic method that is used in oncology as palliative treatment in patients with recurrent head and neck tumors and who are not candidates for standard therapeutic options. The aim of our study was to evaluate the cytoreductive effect of ECT in patients subjected to chemoradiotherapy for squamous cell carcinoma of the oral cavity. The primary endpoint of the study was to verify tumor debulking after ECT treatment as neoadjuvant, before conventional chemoradiotherapy. The secondary endpoint was to assess the safety and tolerability of ECT treatment. Materials and methods This experimental study was conducted at the Division of Otolaryngology, University of Catanzaro, Italy. From February 2013 to February 2014, four patients were enrolled, two males and two females, with a mean age of 56 years (range: 47–65 years), and with squamous cell carcinoma of the oral cavity in advanced stages of disease (T3–T4). All patients, with their informed consent, received ECT treatment in accordance with the Standard Operating Procedures defined in the European Standard Operating Procedures on Electrochemotherapy (ESOPE) study, followed by conventional chemoradiotherapy. Their response to ECT treatment was assessed after 30 days. For each patient, the following parameters were evaluated with the appropriate forms: local tumor control, control of pain (analgesia postsurgery scale [APS]), and quality of life (Short Form [36] Health Survey [SF-36]; v1). Results Three of four patients (75%) showed a partial response, whereas in one patient (25%), the disease remained stable. The treatment was well-tolerated by all patients, according to the APS and SF-36 results. Conclusion Although the study was conducted on a small number of cases, data from this study show that ECT represents a safe and effective treatment in terms of tumor cytoreduction and locoregional control of the disease. It also allows good control of postoperative pain

  18. Weekly Low-Dose Docetaxel-Based Chemoradiotherapy for Locally Advanced Oropharyngeal or Hypopharyngeal Carcinoma: A Retrospective, Single-Institution Study

    SciTech Connect

    Fukada, Junichi; Shigematsu, Naoyuki; Takeda, Atsuya; Ohashi, Toshio; Tomita, Toshiki; Shiotani, Akihiro; Kunieda, Etsuo; Kawaguchi, Osamu; Fujii, Masato; Kubo, Atsushi

    2010-02-01

    Purpose: To retrospectively assess the efficacy, toxicity, and prognostic factors of weekly low-dose docetaxel-based chemoradiotherapy for Stage III/IV oropharyngeal or hypopharyngeal carcinoma. Methods and Materials: Between 2001 and 2005, 72 consecutive patients with locally advanced oropharyngeal or hypopharyngeal carcinoma were treated with concurrent chemoradiotherapy (CCR; radiation at 60 Gy plus weekly docetaxel [10 mg/m{sup 2}]). Thirty of these patients also received neoadjuvant chemotherapy (NAC; docetaxel, cisplatin, and 5-fluorouracil) before concurrent chemoradiotherapy. Survival was calculated according to the Kaplan-Meier method. The prognostic factors were evaluated by univariate and multivariate analyses. Results: The median follow-up was 33 months, with overall survival, disease-free survival, and locoregional control rates at 3 years of 59%, 45%, and 52%, respectively. Thirty-six patients (50%) experienced more than one Grade 3 to 4 acute toxicity. Grade 3 mucositis occurred in 32 patients (44%), Grade 4 laryngeal edema in 1 (1%). Grade >=3 severe hematologic toxicity was observed in only 2 patients (3%). Grade 3 dysphagia occurred as a late complication in 2 patients (3%). Multivariate analyses identified age, T stage, hemoglobin level, and completion of weekly docetaxel, but not NAC, as significant factors determining disease-free survival. Conclusions: Docetaxel is an active agent used in both concurrent and sequential chemoradiotherapy regimens. Mucositis was the major acute toxicity, but this was well tolerated in most subjects. Anemia was the most significant prognostic factor determining survival. Further studies are warranted to investigate the optimal protocol for integrating docetaxel into first-line chemoradiotherapy regimens, as well as the potential additive impact of NAC.

  19. MRI assisted cervix cancer brachytherapy pre-planning, based on insertion of the applicator in para-cervical anaesthesia: preliminary results of a prospective study

    PubMed Central

    Hudej, Robert; Music, Maja

    2009-01-01

    Purpose To report on preliminary results of a prospective study on MRI-assisted cervix cancer brachytherapy pre-planning. Material and methods In six locally advanced cervix cancer patients, five days before the first brachytherapy fraction, tandem & ring applicator was inserted under para-cervical anaesthesia, MRI performed and applicator removed. Procedure-time and patient-tolerability were recorded. High risk CTV and organs at risk were delineated, virtual needles placed and dose planning performed. At brachytherapy, insertion was carried out under subarachnoidal anaesthesia, according to pre-planned geometry. Pre-planned and actual needle positions and DVH parameters were compared. Results The procedure was well tolerated and short. All inserted needles were inside high risk CTV and outside organs at risk. Differences in pre-planned and actual DVH parameters and implant geometry were small. Conclusions The procedure was well tolerated and feasible. Pre-planned geometry could be reproduced thoroughly at brachytherapy application.

  20. Orbital Metastasis of Cervical Carcinoma – Case Report and Review of Literature

    PubMed Central

    Arthur, Anupriya; Horo, Saban; Balasubramanian, Dhipak Arthur; Ram, Thomas Samuel; Peter, John Victor

    2016-01-01

    The orbit is a frequent site of metastasis, particularly from the breast, prostate gland and the lung. Carcinoma of the cervix metastasizing to the orbit is rare. We report a 27-year-old woman with Stage II B cervical cancer who presented with progressive painless protrusion of the left eye of one month duration associated with diplopia. Histology of the orbital mass was similar to that of the cervical cancer and reported as squamous cell carcinoma. She received palliative radiation to the left orbit 30 Gy in 10 fractions along with chemotherapy (Paclitaxel and Carboplatin). This resulted in regression of the proptosis. We review published literature of cases of carcinoma of the uterine cervix with metastasis to the orbit. PMID:26894102

  1. Prognostic Value of Neoadjuvant Chemotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma with Low Pre-treatment Epstein-Barr Virus DNA: a Propensity-matched Analysis

    PubMed Central

    Peng, Hao; Chen, Lei; Li, Wen-Fei; Guo, Rui; Zhang, Yuan; Zhang, Fan; Liu, Li-Zhi; Tian, Li; Lin, Ai-Hua; Sun, Ying; Ma, Jun

    2016-01-01

    Background: The aim of this study is to investigate the prognostic value of neoadjuvant chemotherapy (NCT) in locoregionally advanced nasopharyngeal carcinoma (NPC) with low pre-treatment Epstein-Barr virus (EBV) DNA in the era of intensity-modulated radiotherapy (IMRT). Methods: Data on 1099 locoregionally advanced NPC patients treated with IMRT were retrospectively reviewed. Propensity score matching (PSM) method was adopted to balance influence of covariates. Patient survival between NCT and non-NCT groups were compared. Results: The cut-off value of pre-treatment Epstein-Barr virus DNA (pre-DNA) was 1550 copies/ml for DMFS (area under curve [AUC], 0.655; sensitivity, 0.819; specificity, 0.445). For the 145 pairs selected by PSM, the 3-year distant metastasis-free survival (DMFS), overall survival (OS), disease-free survival (DFS) and locoregional relapse-free survival (LRRFS) rates were 98.6% vs. 93.7% (P = 0.101), 95.8% vs. 94.4% (P = 0.881), 91.7% vs. 87.5% (P = 0.309) and 94.4% vs. 95.0% (P = 0.667), respectively. Multivariate analysis did not identify NCT as an independent prognostic factor (P > 0.05 for all rates), and stratified analysis based on overall stage (III and IV) and N category (N0-1 and N2-3) also got the same results. Conclusion: NCT was not established as an independent prognostic factor, and it should not be used in locoregionally advanced NPC with low pre-DNA. PMID:27471562

  2. High RAB25 expression is associated with good clinical outcome in patients with locally advanced head and neck squamous cell carcinoma

    PubMed Central

    Téllez-Gabriel, Marta; Arroyo-Solera, Irene; León, Xavier; Gallardo, Alberto; López, Montserrat; Céspedes, Maria V; Casanova, Isolda; López-Pousa, Antonio; Quer, Miquel; Mangues, Maria A; Barnadas, Agustí; Mangues, Ramón; Pavón, Miguel A

    2013-01-01

    Currently there are no molecular markers able to predict clinical outcome in locally advanced head and neck squamous cell carcinoma (HNSCC). In a previous microarray study, RAB25 was identified as a potential prognostic marker. The aim of this study was to analyze the association between RAB25 expression and clinical outcome in patients with locally advanced HNSCC treated with standard therapy. In a retrospective immunohistochemical study (n = 97), we observed that RAB25-negative tumors had lower survival (log-rank, P = 0.01) than patients bearing positive tumors. In an independent prospective mRNA study (n = 117), low RAB25 mRNA expression was associated with poor prognosis. Using classification and regression tree analysis (CART) we established two groups of patients according to their RAB25 mRNA level and their risk of death. Low mRNA level was associated with poor local recurrence-free (log-rank, P = 0.005), progression-free (log-rank, P = 0.002) and cancer-specific (log-rank, P < 0.001) survival. Multivariate Cox model analysis showed that low expression of RAB25 was an independent poor prognostic factor for survival (hazard ratio: 3.84, 95% confidence interval: 1.93–7.62, P < 0.001). Patients whose tumors showed high RAB25 expression had a low probability of death after treatment. We also found lower RAB25 expression in tumors than in normal tissue (Mann–Whitney U, P < 0.001). Moreover, overexpression of RAB25 in the UM-SCC-74B HNSCC cell line increased cisplatin sensitivity, and reduced cell migration and invasion. Our findings support a tumor suppressor role for RAB25 in HNSCC and its potential use to identify locally advanced patients with a high probability of survival after genotoxic treatment. PMID:24403269

  3. Surgery for Intermediate and Advanced Hepatocellular Carcinoma: A Consensus Report from the 5th Asia-Pacific Primary Liver Cancer Expert Meeting (APPLE 2014)

    PubMed Central

    Ho, Ming-Chih; Hasegawa, Kiyoshi; Chen, Xiao-Ping; Nagano, Hiroaki; Lee, Young-Joo; Chau, Gar-Yang; Zhou, Jian; Wang, Chih-Chi; Choi, Young Rok; Poon, Ronnie Tung-Ping; Kokudo, Norihiro

    2016-01-01

    Background The Barcelona Clinic Liver Cancer (BCLC) staging and treatment strategy does not recommended surgery for treating BCLC stage B and C hepatocellular carcinoma (HCC). However, numerous Asia-Pacific institutes still perform surgery for this patient group. This consensus report from the 5th Asia-Pacific Primary Liver Cancer Expert Meeting aimed to share opinions and experiences pertaining to liver resection for intermediate and advanced HCCs and to provide evidence to issue recommendations for surgery in this patient group. Summary Thirteen experts from five Asia-Pacific regions were invited to the meeting; 10 of them (Japan: 2, Taiwan: 3, South Korea: 2, Hong Kong: 1, and China: 2) voted for the final consensus. The discussion focused on evaluating the preoperative liver functional reserve and surgery for large tumors, multiple tumors, HCCs with vascular invasion, and HCCs with distant metastasis. The feasibility of future prospective randomized trials comparing surgery with transarterial chemoembolization for intermediate HCC and with sorafenib for advanced HCC was also discussed. The Child-Pugh score (9/10 experts) and indocyanine green retention rate at 15 min (8/10) were the most widely accepted methods for evaluating the preoperative liver functional reserve. All (10/10) experts agreed that portal hypertension, tumor size >5 cm, portal venous invasion, hepatic venous invasion, and extrahepatic metastasis are not absolute contraindications for the surgical resection of HCC. Furthermore, 9 of the 10 experts agreed that tumor resection may be performed for patients with >3 tumors. The limitations of surgery are associated with a poor liver functional reserve, incomplete tumor resection, and a high probability of recurrence. Key Messages Surgery provides significant survival benefits for Asian-Pacific patients with intermediate and advanced HCCs, particularly when the liver functional reserve is favorable. However, prospective randomized controlled trials

  4. High RAB25 expression is associated with good clinical outcome in patients with locally advanced head and neck squamous cell carcinoma.

    PubMed

    Téllez-Gabriel, Marta; Arroyo-Solera, Irene; León, Xavier; Gallardo, Alberto; López, Montserrat; Céspedes, Maria V; Casanova, Isolda; López-Pousa, Antonio; Quer, Miquel; Mangues, Maria A; Barnadas, Agustí; Mangues, Ramón; Pavón, Miguel A

    2013-12-01

    Currently there are no molecular markers able to predict clinical outcome in locally advanced head and neck squamous cell carcinoma (HNSCC). In a previous microarray study, RAB25 was identified as a potential prognostic marker. The aim of this study was to analyze the association between RAB25 expression and clinical outcome in patients with locally advanced HNSCC treated with standard therapy. In a retrospective immunohistochemical study (n = 97), we observed that RAB25-negative tumors had lower survival (log-rank, P = 0.01) than patients bearing positive tumors. In an independent prospective mRNA study (n = 117), low RAB25 mRNA expression was associated with poor prognosis. Using classification and regression tree analysis (CART) we established two groups of patients according to their RAB25 mRNA level and their risk of death. Low mRNA level was associated with poor local recurrence-free (log-rank, P = 0.005), progression-free (log-rank, P = 0.002) and cancer-specific (log-rank, P < 0.001) survival. Multivariate Cox model analysis showed that low expression of RAB25 was an independent poor prognostic factor for survival (hazard ratio: 3.84, 95% confidence interval: 1.93-7.62, P < 0.001). Patients whose tumors showed high RAB25 expression had a low probability of death after treatment. We also found lower RAB25 expression in tumors than in normal tissue (Mann-Whitney U, P < 0.001). Moreover, overexpression of RAB25 in the UM-SCC-74B HNSCC cell line increased cisplatin sensitivity, and reduced cell migration and invasion. Our findings support a tumor suppressor role for RAB25 in HNSCC and its potential use to identify locally advanced patients with a high probability of survival after genotoxic treatment. PMID:24403269

  5. Oxaliplatin Plus Dual Inhibition of Thymidilate Synthase During Preoperative Pelvic Radiotherapy for Locally Advanced Rectal Carcinoma: Long-Term Outcome

    SciTech Connect

    Avallone, Antonio; Delrio, Paolo; Pecori, Biagio; Tatangelo, Fabiana; Petrillo, Antonella; Scott, Nigel; Marone, Pietro; Aloi, Luigi; Sandomenico, Claudia; Lastoria, Secondo; Iaffaioli, Vincenzo Rosario; Scala, Dario; Iodice, Giovanni; Budillon, Alfredo; Comella, Pasquale

    2011-03-01

    Purpose: To assess the safety and efficacy of oxaliplatin (OXA) plus dual inhibition of thymidilate synthase during preoperative pelvic radiotherapy (RT) in patients with poor prognosis for rectal carcinoma. Methods and Materials: Sixty-three patients with the following characteristics, a clinical (c) stage T4, cN1-2, or cT3N0 of {<=}5 cm from the anal verge and/or with a circumferential resection margin (CRM) of {<=}5 mm (by magnetic resonance imaging), received three biweekly courses of chemotherapy with OXA, 100 mg/m{sup 2}; raltitrexed (RTX), 2.5 mg/m{sup 2} on day 1, and 5-fluorouracil (5-FU), 900 mg/m{sup 2} (31 patients) or 800 mg/m{sup 2} (32 patients); levo-folinic acid (LFA), 250 mg/m{sup 2} on day 2, during pelvic RT (45 Gy). Pathologic response was defined as complete pathological response (ypCR), major (tumor regression grade(TRG) 2 to 3, with ypCRM-ve and ypN-ve) or minor or no response (TRG4 to -5, or ypCRM+ve, or ypN+ve). Adjuvant 5-FU/LFA regimen was given in cases of cT4, ypN+ve, or ypCRM+ve. Results: Overall, neutropenia (40%) and diarrhea (13%) were the most common grade {>=}3 toxicities, and tolerability was better with a 5-FU dose reduction. No significant difference in pathologic response was seen according 5-FU dosage: overall, a ypCR was obtained in 24 (39%) patients, and a major response in 20 (32%) patients. The 5-year probability of freedom from recurrence was 80% (95% confidence interval, 68%-92%); it was 56% for the minor/no response group, while it was around 90% for both the ypCR and the major response group. Conclusions: OXA, RTX, and 5-FU/LFA administered during pelvic RT produced promising early and long-term results in rectal carcinoma patients with poor prognosis. The postoperative treatment strategy applied in our study supports the risk-adapted approach in postoperative management.

  6. Predictive value of EGFR overexpression and gene amplification on icotinib efficacy in patients with advanced esophageal squamous cell carcinoma

    PubMed Central

    Fan, Qingxia; Lu, Ping; Ma, Changwu; Liu, Wei; Liu, Ying; Li, Weiwei; Hu, Shaoxuan; Ling, Yun; Guo, Lei; Ying, Jianming; Huang, Jing

    2016-01-01

    This study aimed to search for a molecular marker for targeted epithelial growth factor receptor (EGFR) inhibitor Icotinib by analyzing protein expression and amplification of EGFR proto-oncogene in esophageal squamous cell carcinoma (ESCC) patients. Immunohistochemistry and fluorescence in situ hybridization (FISH) was used to assess EGFR expression and gene amplification status in 193 patients with ESCC. We also examined the association between EGFR overexpression and the efficacy of a novel EGFR TKI, icotinib, in 62 ESCC patients. Of the 193 patients, 95 (49.2%) patients showed EGFR overexpression (3+), and 47(24.4%) patients harbored EGFR FISH positivity. EGFR overexpression was significantly correlated with clinical stage and lymph node metastasis (p<0.05). In addition, EGFR overexpression was significantly correlated with EGFR FISH positivity (p<0.001). Among the 62 patients who received icotinib, the response rate was 17.6% for patients with high EGFR-expressing tumors, which was markedly higher than the rate (0%) for patients with low to moderate EGFR-expressing tumors (p=0.341). Furthermore, all cases responded to icotinib showed EGFR overexpression. In conclusion, our study suggests that EGFR overexpression might potentially be used in predicting the efficacy in patients treated with Icotinib. These data have implications for both clinical trial design and therapeutic strategies. PMID:27013591

  7. Phase I study of tivantinib in Japanese patients with advanced hepatocellular carcinoma: Distinctive pharmacokinetic profiles from other solid tumors.

    PubMed

    Okusaka, Takuji; Aramaki, Takeshi; Inaba, Yoshitaka; Nakamura, Shinichiro; Morimoto, Manabu; Moriguchi, Michihisa; Sato, Takashi; Ikawa, Yuta; Ikeda, Masafumi; Furuse, Junji

    2015-05-01

    A c-Met inhibitor tivantinib is a candidate anticancer agent for patients with hepatocellular carcinoma (HCC), and CYP2C19 is the key metabolic enzyme for tivantinib. Previous Japanese phase I studies in patients with solid tumors (except HCC) recommend 360 mg twice daily (BID) and 240 mg BID for CYP2C19 extensive metabolizers (EM) and poor metabolizers (PM), respectively. In this study, Japanese patients with HCC in whom sorafenib treatment has failed were enrolled to evaluate the safety, tolerability and pharmacokinetics of oral tivantinib as a single agent. The dose was escalated separately in EM and PM, from 120 mg BID to 240 mg BID, in both capsule and tablet formulations. A total of 28 patients (EM: 21, PM: 7) received tivantinib. At a dose of 120 mg BID, dose-limiting toxicities (DLT) did not develop in 12 EM (capsule: 6, tablet: 6) and 7 PM (capsule: 4, tablet: 3) during the DLT-observation period (for 29 days after first dosing). At this dose, the pharmacokinetic profiles of tivantinib (AUC0-12 and Cmax ) did not remarkably differ between EM and PM. When treated with 240 mg BID, 5 of 9 EM (capsule: 4 of 6, tablet: 1 of 3) developed neutropenia-related DLT accompanying plasma tivantinib concentration higher than expected from the previous studies. Consequently, PM did not receive 240 mg BID. In conclusion, 120 mg BID of tivantinib is recommended among Japanese patients with HCC regardless of CYP2C19 phenotype. PMID:25711511

  8. Fractionated intravesical radioimmunotherapy with 213Bi-anti-EGFR-MAb is effective without toxic side-effects in a nude mouse model of advanced human bladder carcinoma

    PubMed Central

    Fazel, Julia; Rötzer, Silvia; Seidl, Christof; Feuerecker, Benedikt; Autenrieth, Michael; Weirich, Gregor; Bruchertseifer, Frank; Morgenstern, Alfred; Senekowitsch-Schmidtke, Reingard

    2015-01-01

    Gold standard in therapy of superficial, non-muscle invasive urothelial tumors is transurethral resection followed by intravesical instillation therapies. However, relapse is commonly observed and therefore new therapeutic approaches are needed. Application of 213Bi-immunoconjugates targeting EGFR had shown promising results in early tumor stages. The aim of this study was the evaluation of fractionated application of 213Bi-anti-EGFR-MAb in advanced tumor stages in a nude mouse model. Luciferase-transfected EJ28 human bladder carcinoma cells were instilled intravesically into nude mice following electrocautery. Tumor development was monitored via bioluminescence imaging. One day after tumor detection mice were treated intravesically either 2 times with 0.93 MBq or 3 times with 0.46 MBq of 213Bi-anti-EGFR-MAb. Therapeutic efficacy was evaluated via overall survival and toxicity toward normal urothelium by histopathological analysis. Mice without treatment and those treated with the native anti-EGFR-MAb showed mean survivals of 65.4 and 57.6 d, respectively. After fractionated treatment with 0.93 MBq of 213Bi-anti-EGFR-MAb animals reached a mean survival of 141.5 d and 33% of the animals survived at least 268 d. Fractionated treatment with 0.46 MBq 213Bi-anti-EGFR-MAb resulted in a mean survival of 131.8 d and 30% of the animals survived longer than 300 d. Significant differences were only observed between the control groups and the group treated twice with 0.93 MBq of 213Bi-anti-EGFR-MAb. No toxic side-effects on the normal urothelium were observed even after treatment with 3.7 MBq of 213Bi-anti-EGFR-MAb. The study demonstrates that the fractionated intravesical radioimmunotherapy with 213Bi-anti-EGFR-MAb is a promising approach in advanced bladder carcinoma. PMID:26177233

  9. [DNA in koilocytotic dysplasia of the cervix uteri, cytophotometric studies].

    PubMed

    Christov, K; Karageosov, I; Makaveeva, V; Kristeva, K

    1987-01-01

    In koilocytotic dysplasia of the uterine cervix the DNA content in squamous cells was quantitated by cytophotometry in histological preparations stained according to Feulgen. Three patterns of DNA distribution in the squamous cells were found. In type one (21.4%) the cells had DNA content in the diploid and paradiploid zone of the histogram. In type two (35.7%) cells with triploid and tetraploid DNA values were found, but with a conspicuous modal class of cells. In type three no modal class cells were found (42.9%). The quantitative DNA changes in squamous cells show that some of the HPV induced alterations may be regarded as precancerous.

  10. The incompetent cervix during pregnancy diagnosed by ultrasound.

    PubMed

    Vaalamo, P; Kivikoski, A

    1983-01-01

    Ninety-one pregnant patients in mid-trimester were examined for suspected cervical incompetence using ultrasound. This diagnosis means that detached membranes at the internal os are bulging into a dilated cervical canal. In 13 cases cervical dilatation was found. These patients were operated on using McDonald's purse-string suture. Only one of these patients had premature rupture of the membranes and was delivered at 35 weeks. In all other operated cases the pregnancy continued beyond 37 weeks. Ultrasound is an objective method of diagnosing incompetence of the cervix in pregnancy. PMID:6683060

  11. Diagnostic ultrasound in the assessment of patients with incompetent cervix.

    PubMed

    Jackson, G; Pendleton, H J; Nichol, B; Wittmann, B K

    1984-03-01

    Twenty-five pregnant women with suspected cervical incompetence were assessed by serial ultrasound. A dilating internal os was documented in one patient, incompetence was ruled out in two, and a 'slipping suture' was demonstrated in another; the remaining patients were subjected to cerclage on the basis of their history alone. Patients in whom the diagnosis of cervical incompetence is indefinite should have a diagnostic ultrasound scan to visualize the cervix for length, opening of the canal and integrity of the internal os. Selective ultrasonography may be beneficial in both the diagnosis and treatment of cervical incompetence. PMID:6704347

  12. Reprint of "Cancer of the cervix: A sexually transmitted infection?".

    PubMed

    Beral, Valerie

    2015-12-01

    When mortality patterns for cancer of the uterine cervix were compared with trends in incidence of sexually transmitted diseases in both England and Wales and in Scotland, there were striking associations between the temporal, social class, occupational, and geographic distributions of these diseases. The data suggest that exposure to sexually transmitted infection is an important determinant of cervical cancer. Although they are still young, women born after 1940 are already experiencing increased cervical-cancer mortality. If cervical-cancer prevention and therapy remain unchanged, this generation's high risk of death from cervical cancer will probably continue to operate throughout their lives.

  13. The Changes of Lipid Metabolism in Advanced Renal Cell Carcinoma Patients Treated with Everolimus: A New Pharmacodynamic Marker?

    PubMed Central

    Pantano, Francesco; Santoni, Matteo; Procopio, Giuseppe; Rizzo, Mimma; Iacovelli, Roberto; Porta, Camillo; Conti, Alessandro; Lugini, Antonio; Milella, Michele; Galli, Luca; Ortega, Cinzia; Guida, Francesco Maria; Silletta, Marianna; Schinzari, Giovanni; Verzoni, Elena; Modica, Daniela; Crucitti, Pierfilippo; Rauco, Annamaria; Felici, Alessandra; Ballatore, Valentina; Cascinu, Stefano; Tonini, Giuseppe; Carteni, Giacomo; Russo, Antonio; Santini, Daniele

    2015-01-01

    Background Everolimus is a mammalian target of rapamycin (mTOR) inhibitor approved for the treatment of metastatic renal cell carcinoma (mRCC). We aimed to assess the association between the baseline values and treatmentrelated modifications of total serum cholesterol (C), triglycerides (T), body mass index (BMI), fasting blood glucose level (FBG) and blood pressure (BP) levels and the outcome of patients treated with everolimus for mRCC. Methods 177 patients were included in this retrospective analysis. Time to progression (TTP), clinical benefit (CB) and overall survival (OS) were evaluated. Results Basal BMI was significantly higher in patients who experienced a CB (p=0,0145). C,T and C+T raises were significantly associated with baseline BMI (p=0.0412, 0.0283 and 0.0001). Median TTP was significantly longer in patients with T raise compared to patients without T (10 vs 6, p=0.030), C (8 vs 5, p=0.042) and C+T raise (10.9 vs 5.0, p=0.003). At the multivariate analysis, only C+T increase was associated with improved TTP (p=0.005). T raise (21.0 vs 14.0, p=0.002) and C+T increase (21.0 vs 14.0, p=0.006) were correlated with improved OS but were not significant at multivariate analysis. Conclusion C+T raise is an early predictor for everolimus efficacy for patients with mRCC. PMID:25885920

  14. A dosimetric analysis of dose escalation using two intensity-modulated radiation therapy techniques in locally advanced pancreatic carcinoma

    SciTech Connect

    Brown, Michael W.; Ning, Holly; Arora, Barbara; Albert, Paul S.; Poggi, Matthew; Camphausen, Kevin; Citrin, Deborah . E-mail: citrind@mail.nih.gov

    2006-05-01

    Purpose: To perform an analysis of three-dimensional conformal radiation therapy (3D-CRT), sequential boost intensity-modulated radiation therapy (IMRTs), and integrated boost IMRT (IMRTi) for dose escalation in unresectable pancreatic carcinoma. Methods and Materials: Computed tomography images from 15 patients were used. Treatment plans were generated using 3D-CRT, IMRTs, and IMRTi for dose levels of 54, 59.4, and 64.8 Gy. Plans were analyzed for target coverage, doses to liver, kidneys, small bowel, and spinal cord. Results: Three-dimensional-CRT exceeded tolerance to small bowel in 1 of 15 (6.67%) patients at 54 Gy, and 4 of 15 (26.7%) patients at 59.4 and 64.8 Gy. 3D-CRT exceeded spinal cord tolerance in 1 of 15 patients (6.67%) at 59.4 Gy and liver constraints in 1 of 15 patients (6.67%) at 64.8 Gy; no IMRT plans exceeded tissue tolerance. Both IMRT techniques reduced the percentage of total kidney volume receiving 20 Gy (V20), the percentage of small bowel receiving 45 Gy (V45), and the percentage of liver receiving 35 Gy (V35). IMRTi appeared superior to IMRTs in reducing the total kidney V20 (p < 0.0001), right kidney V20 (p < 0.0001), and small bowel V45 (p = 0.02). Conclusions: Sequential boost IMRT and IMRTi improved the ability to achieve normal tissue dose goals compared with 3D-CRT. IMRTi allowed dose escalation to 64.8 Gy with acceptable normal tissue doses and superior dosimetry compared with 3D-CRT and IMRTs.

  15. Bilateral ovarian squamous cell carcinoma with an antecedent dermoid cyst in the left ovary.

    PubMed

    Prasad, Sruthi; Suguna, B V; Ravindra, Savithri

    2011-09-01

    Ovarian squamous cell carcinoma is a rare malignancy and its occurrence is commonly attributed to malignant transformation of a pre-existing mature cystic teratoma. The de novo occurrence of primary squamous cell carcinoma is extremely rare. Malignant transformation in a mature cystic teratoma is almost always unilateral; however, there have been isolated reports of an uncomplicated mature cystic teratoma in the contralateral ovary. We report here a case of a 40-year-old woman presenting with squamous cell carcinoma of both ovaries with antecedent dermoid cyst in the left ovary, along with involvement of the fallopian tubes, cervix and omentum.

  16. Comparison of cisplatinum/paclitaxel with cisplatinum/5-fluorouracil as first-line therapy for nonsurgical locally advanced esophageal squamous cell carcinoma patients

    PubMed Central

    Hu, Guofang; Wang, Zhehai; Wang, Yuan; Zhang, Qingqing; Tang, Ning; Guo, Jun; Liu, Liyan; Han, Xiao

    2016-01-01

    Background To retrospectively evaluate the efficacy and toxicity of definitive concurrent chemoradiotherapy (dCRT) with cisplatinum/paclitaxel versus cisplatinum/5-fluorouracil in patients with locally advanced esophageal squamous cell carcinoma (ESCC) who received nonsurgical treatment. Methods This study retrospectively evaluated 202 patients with locally advanced ESCC treated at Shandong Cancer Hospital between January 2009 and December 2013. All the patients initially received dCRT, including platinum and paclitaxel or 5-fluorouracil, with concurrent 1.8 or 2 Gy/fraction radiation (total dose, 54–60 Gy). The patient population was divided into two treatment groups: 105 patients who received the cisplatinum/paclitaxel regimen were allocated to group A, and 97 patients who received the cisplatinum/5-fluorouracil regimen were allocated to group B. We compared the progression-free survival (PFS) and overall survival (OS) by various clinical variables, including prior treatment characteristics, major toxicities (mainly in grade 3 and 4 hematological), and response to dCRT. We used the receiver operating curve analysis to determine the optimal cutoff value of clinical stage and radiation dose. The Kaplan–Meier method was used for survival comparison and Cox regression for multivariate analysis. Results Median PFS and OS in group A were significantly better compared with group B (median PFS, 15.9 versus 13.0 months, P=0.016 and median OS, 33.9 versus 23.1 months, P=0.014, respectively). The 1- and 2-year survival rates of the two groups were 82.9% versus 76.3%, and 61.9% versus 47.6%, respectively. The complete response and response rate were 17.1% versus 7.2% (P=0.032) and 52.4% versus 30.9% (P=0.042) in group A and B, respectively. Meanwhile, group B was associated with a significantly lower rate of grade 3/4 overall toxicity than group A (P=0.039). Conclusion Our data showed that patients with locally advanced ESCC in group A had longer PFS and OS compared with

  17. Outcomes in a Multi-institutional Cohort of Patients Treated With Intraoperative Radiation Therapy for Advanced or Recurrent Renal Cell Carcinoma

    SciTech Connect

    Paly, Jonathan J.; Hallemeier, Christopher L.; Biggs, Peter J.; Niemierko, Andrzej; Roeder, Falk; Martínez-Monge, Rafael; Whitson, Jared; Calvo, Felipe A.; Fastner, Gerd; Sedlmayer, Felix; Wong, William W.; Ellis, Rodney J.; Haddock, Michael G.; Choo, Richard; Shipley, William U.; Zietman, Anthony L.; Efstathiou, Jason A.

    2014-03-01

    Purpose/Objective(s): This study aimed to analyze outcomes in a multi-institutional cohort of patients with advanced or recurrent renal cell carcinoma (RCC) who were treated with intraoperative radiation therapy (IORT). Methods and Materials: Between 1985 and 2010, 98 patients received IORT for advanced or locally recurrent RCC at 9 institutions. The median follow-up time for surviving patients was 3.5 years. Overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) were estimated with the Kaplan-Meier method. Chained imputation accounted for missing data, and multivariate Cox hazards regression tested significance. Results: IORT was delivered during nephrectomy for advanced disease (28%) or during resection of locally recurrent RCC in the renal fossa (72%). Sixty-nine percent of the patients were male, and the median age was 58 years. At the time of primary resection, the T stages were as follows: 17% T1, 12% T2, 55% T3, and 16% T4. Eighty-seven percent of the patients had a visibly complete resection of tumor. Preoperative or postoperative external beam radiation therapy was administered to 27% and 35% of patients, respectively. The 5-year OS was 37% for advanced disease and 55% for locally recurrent disease. The respective 5-year DSS was 41% and 60%. The respective 5-year DFS was 39% and 52%. Initial nodal involvement (hazard ratio [HR] 2.9-3.6, P<.01), presence of sarcomatoid features (HR 3.7-6.9, P<.05), and higher IORT dose (HR 1.3, P<.001) were statistically significantly associated with decreased survival. Adjuvant systemic therapy was associated with decreased DSS (HR 2.4, P=.03). For locally recurrent tumors, positive margin status (HR 2.6, P=.01) was associated with decreased OS. Conclusions: We report the largest known cohort of patients with RCC managed by IORT and have identified several factors associated with survival. The outcomes for patients receiving IORT in the setting of local recurrence compare favorably to

  18. Tannic acid binding of cell surfaces in normal, premalignant, and malignant squamous epithelium of the human uterine cervix.

    PubMed

    Davina, J H; Lamers, G E; van Haelst, U J; Kenemans, P; Stadhouders, A M

    1984-01-01

    Alterations in tannic acid (TA) binding capacity of cell surface carbohydrates in normal, premalignant, and malignant squamous epithelium of the human uterine cervix have been studied using electron microscopic visualization in combination with microdensitometric evaluation. While in normal epithelium there is distinct binding in four to five cell layers of the deep intermediate zone, cells of carcinoma in situ and invasive cancer lesions lack TA binding. In moderate dysplasia an intermediate reacting pattern is found. Deep intermediate cells in areas bordering the carcinoma in situ lesions do not show any binding, although their ultrastructure cannot be distinguished from similar cells in normal tissue. The TA deposition within the deep intermediate zone is probably related to the presence here of glycoprotein-containing membrane-coating granules. The finding that TA binding discriminates between cells in normal squamous epithelium and morphologically normal cells in juxtaposition with lesional areas in premalignant and malignant epithelium opens the possibility for a more reliable cytologic diagnosis of cervical epithelial neoplasia.

  19. Apparent diffusion coefficient values detected by diffusion-weighted imaging in the prognosis of patients with locally advanced esophageal squamous cell carcinoma receiving chemoradiation

    PubMed Central

    Liu, Shu; Zhen, Fuxi; Sun, Nana; Chen, Jiayan; Cao, Yuandong; Zhang, Sheng; Cheng, Hongyan; Ge, Xiaolin; Sun, Xinchen

    2016-01-01

    Purpose Previous studies have demonstrated that apparent diffusion coefficient (ADC) values measured by magnetic resonance imaging have prognostic value in patients with esophageal squamous cell carcinoma (ESCC). However, the role of ADC needs to be validated in a cohort of Chinese ESCC patients. This study assessed the role of ADC in predicting the outcome of patients with ESCC treated only by chemoradiation in the People’s Republic of China. Patients and methods Seventy-three patients with local advanced ESCC were retrospectively analyzed in this study; none of the patients underwent surgery before or after chemoradiation. The ADC values of the primary tumors were determined by magnetic resonance imaging. The ADC values were then correlated with clinicopathological and other radiological parameters. Survival analysis was carried out to determine if ADC had an impact on survival of these patients. Results The median ADC value of the esophageal cancer tissue was 1.256*10−3 mm2/sec (range: 0.657–2.354*10−3 mm2/sec, interquartile range 0.606*10−3 mm2/sec). No clinicopathological or radiological parameters were associated with the ADC values except the sites of tumor tissues. ADC <1.076*10−3 mm2/sec predicted significantly worse survival in patients with ESCC (12.9 months vs undefined, P=0.0108). Conclusion The ADC value is a potent prognostic factor which can be used to predict the outcome of patients with ESCC treated only by chemoradiation. PMID:27703377

  20. Prognostic significance of catalase expression and its regulatory effects on hepatitis B virus X protein (HBx) in HBV-related advanced hepatocellular carcinomas.

    PubMed

    Cho, Mi-Young; Cheong, Jae Youn; Lim, Wonchung; Jo, Sujin; Lee, Youngsoo; Wang, Hee-Jung; Han, Kyou-Hoon; Cho, Hyeseong

    2014-12-15

    Hepatitis B virus X protein (HBx) plays a role in liver cancer development. We previously showed that ROS increased HBx levels and here, we investigated the role of antioxidants in the regulation of HBx expression and their clinical relevance. We found that overexpression of catalase induced a significant loss in HBx levels. The cysteine null mutant of HBx (Cys-) showed a dramatic reduction in its protein stability. In clonogenic proliferation assays, Huh7-X cells produced a significant number of colonies whereas Huh7-Cys- cells failed to generate them. The Cys at position 69 of HBx was crucial to maintain its protein stability and transactivation function in response to ROS. Among 50 HBV-related hepatocellular carcinoma (HCC) specimens, 72% of HCCs showed lower catalase levels than those of surrounding non-tumor tissues. In advanced stage IV, catalase levels in non-tumor tissues were increased whereas those in tumors were further reduced. Accordingly, patients with a high T/N ratio for catalase showed significantly longer survival than those with a low T/N ratio. Together, catalase expression in HCC patients can be clinically useful for prediction of patient survival, and restoration of catalase expression in HCCs could be an important strategy for intervention in HBV-induced liver diseases.

  1. Bioinformatics Analysis Reveals Distinct Molecular Characteristics of Hepatitis B-Related Hepatocellular Carcinomas from Very Early to Advanced Barcelona Clinic Liver Cancer Stages.

    PubMed

    Kong, Fan-Yun; Wei, Xiao; Zhou, Kai; Hu, Wei; Kou, Yan-Bo; You, Hong-Juan; Liu, Xiao-Mei; Zheng, Kui-Yang; Tang, Ren-Xian

    2016-01-01

    Hepatocellular carcinoma (HCC)is the fifth most common malignancy associated with high mortality. One of the risk factors for HCC is chronic hepatitis B virus (HBV) infection. The treatment strategy for the disease is dependent on the stage of HCC, and the Barcelona clinic liver cancer (BCLC) staging system is used in most HCC cases. However, the molecular characteristics of HBV-related HCC in different BCLC stages are still unknown. Using GSE14520 microarray data from HBV-related HCC cases with BCLC stages from 0 (very early stage) to C (advanced stage) in the gene expression omnibus (GEO) database, differentially expressed genes (DEGs), including common DEGs and unique DEGs in different BCLC stages, were identified. These DEGs were located on different chromosomes. The molecular functions and biology pathways of DEGs were identified by gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and the interactome networks of DEGs were constructed using the NetVenn online tool. The results revealed that both common DEGs and stage-specific DEGs were associated with various molecular functions and were involved in special biological pathways. In addition, several hub genes were found in the interactome networks of DEGs. The identified DEGs and hub genes promote our understanding of the molecular mechanisms underlying the development of HBV-related HCC through the different BCLC stages, and might be used as staging biomarkers or molecular targets for the treatment of HCC with HBV infection. PMID:27454179

  2. Induction chemotherapy with concurrent chemoradiotherapy versus concurrent chemoradiotherapy for locally advanced squamous cell carcinoma of head and neck: a meta-analysis

    PubMed Central

    Zhang, Lijuan; Jiang, Nan; Shi, Yuexian; Li, Shipeng; Wang, Peiguo; Zhao, Yue

    2015-01-01

    Concurrent chemoradiotherapy (CCRT) has been considered to be the standard of care for locally advanced squamous cell carcinoma of head and neck (LA-SCCHN). Whether induction chemotherapy (IC) with CCRT will further improve the clinical outcomes or not is still unclear. We conducted a meta-analysis to compare the two regimens for LA-SCCHN. Literature searches were carried out in PubMed, Embase, Cochrane Library and Chinese Biology Medicine from inception to November 2014. Five prospective randomized controlled trials (RCTs) with 922 patients were included in meta-analysis. Results were expressed as hazard ratios (HRs) or relative risks (RRs) with 95% confidence intervals (CIs). Compared with CCRT, IC with CCRT showed no statistically significant differences in overall survival (OS), progression-free survival (PFS), overall response rate (ORR) or locoregional recurrence rate (LRR), but could increase risks of grade 3–4 febrile neutropenia (P = 0.0009) and leukopenia (P = 0.04). In contrast, distant metastasis rate (DMR) decreased (P = 0.006) and complete response rate (CR) improved (P = 0.010) for IC with CCRT. In conclusion, the current studies do not support the use of IC with CCRT over CCRT, and the further positioning of IC with CCRT as standard treatment for LA-SCCHN will come from more RCTs directly comparing IC followed by CCRT with CCRT. PMID:26041604

  3. Prognostic Potential and Tumor Growth–Inhibiting Effect of Plasma Advanced Glycation End Products in Non–Small Cell Lung Carcinoma

    PubMed Central

    Bartling, Babett; Hofmann, Hans-Stefan; Sohst, Antonia; Hatzky, Yvonne; Somoza, Veronika; Silber, Rolf-Edgar; Simm, Andreas

    2011-01-01

    The plasma fluorescence related to the standard fluorescence of advanced glycation end products (AGEs) is a simple measurable blood parameter for distinct diseases but its importance in human cancer, including non–small cell lung carcinoma (NSCLC), is unknown. Plasma samples of 70 NSCLC patients who underwent resection surgery of the tumor were analyzed for the distinct AGE-related fluorescence at 370 nm excitation/440 nm emission. In a retrospective study, we tested the prognostic relevance of this AGE-related plasma fluorescence. The effect of circulating AGEs on the NSCLC growth was studied experimentally in vitro and in vivo. NSCLC patients with high (> median) AGE-related plasma fluorescence were characterized by a later reoccurrence of the tumor after curative surgery and a higher survival rate compared with patients with low plasma fluorescence (25% versus 47% 5-y survival, P = 0.011). Treating NSCLC cell spheroids with patients’ plasma showed an inverse correlation between the growth of spheroids in vitro and the individual AGE-related fluorescence of each plasma sample. To confirm the impact of circulating AGEs on the NSCLC progression, we studied the NSCLC growth in mice whose circulating AGE level was elevated by AGE-rich diet. In vivo tumorigenicity assays demonstrated that mice with higher levels of circulating AGEs developed smaller tumors than mice with normal AGE levels. The AGE-related plasma fluorescence has prognostic relevance for NSCLC patients in whom the tumor growth-inhibiting effect of circulating AGEs might play a critical role. PMID:21629968

  4. Bioinformatics Analysis Reveals Distinct Molecular Characteristics of Hepatitis B-Related Hepatocellular Carcinomas from Very Early to Advanced Barcelona Clinic Liver Cancer Stages

    PubMed Central

    Hu, Wei; Kou, Yan-Bo; You, Hong-Juan; Liu, Xiao-Mei; Zheng, Kui-Yang; Tang, Ren-Xian

    2016-01-01

    Hepatocellular carcinoma (HCC)is the fifth most common malignancy associated with high mortality. One of the risk factors for HCC is chronic hepatitis B virus (HBV) infection. The treatment strategy for the disease is dependent on the stage of HCC, and the Barcelona clinic liver cancer (BCLC) staging system is used in most HCC cases. However, the molecular characteristics of HBV-related HCC in different BCLC stages are still unknown. Using GSE14520 microarray data from HBV-related HCC cases with BCLC stages from 0 (very early stage) to C (advanced stage) in the gene expression omnibus (GEO) database, differentially expressed genes (DEGs), including common DEGs and unique DEGs in different BCLC stages, were identified. These DEGs were located on different chromosomes. The molecular functions and biology pathways of DEGs were identified by gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and the interactome networks of DEGs were constructed using the NetVenn online tool. The results revealed that both common DEGs and stage-specific DEGs were associated with various molecular functions and were involved in special biological pathways. In addition, several hub genes were found in the interactome networks of DEGs. The identified DEGs and hub genes promote our understanding of the molecular mechanisms underlying the development of HBV-related HCC through the different BCLC stages, and might be used as staging biomarkers or molecular targets for the treatment of HCC with HBV infection. PMID:27454179

  5. Ultrasonic assessment of cervix in 'at risk' patients.

    PubMed

    Varma, T R; Patel, R H; Pillai, U

    1986-01-01

    One hundred and fifteen women were considered to be at risk of cervical incompetence, judging from their previous history. They were scanned serially from the first trimester to 32 weeks of gestation. Of the 115, 75 women were found to have defective cervix, as assessed on the basis of its length, its overall width and the width of the cervical canal at the level of the internal cervical os, and herniation of the amniotic membrane, with or without fetal parts, into the cervical canal. Sixteen of the 75 women with ultrasonically diagnosed cervical incompetence aborted, 40 needed cervical cerclage, 24 gave birth premature (24 to 34 weeks). Of the 115 women, 40 did not have ultrasonic evidence of cervical incompetence and only one patient gave birth at 36 weeks' gestation, while 39 patients gave birth between 37 and 42 weeks. These 40 women would have had cervical cerclage on the basis of clinical history alone. Ultrasound is an objective method of diagnosing the incompetent cervix and also helps to avoid unnecessary cerclage operations on the basis of history alone. PMID:3524097

  6. Denoising of Ultrasound Cervix Image Using Improved Anisotropic Diffusion Filter

    PubMed Central

    Rose, R Jemila; Allwin, S

    2015-01-01

    ABSTRACT Objective: The purpose of this study was to evaluate an improved oriented speckle reducing anisotropic diffusion (IADF) filter that suppress the speckle noise from ultrasound B-mode images and shows better result than previous filters such as anisotropic diffusion, wavelet denoising and local statistics. Methods: The clinical ultrasound images of the cervix were obtained by ATL HDI 5000 ultrasound machine from the Regional Cancer Centre, Medical College campus, Thiruvananthapuram. The standardized ways of organizing and storing the image were in the format of bmp and the dimensions of 256 × 256 with the help of an improved oriented speckle reducing anisotropic diffusion filter. For analysis, 24 ultrasound cervix images were tested and the performance measured. Results: This provides quality metrics in the case of maximum peak signal-to-noise ratio (PSNR) of 31 dB, structural similarity index map (SSIM) of 0.88 and edge preservation accuracy of 88%. Conclusion: The IADF filter is the optimal method and it is capable of strong speckle suppression with less computational complexity. PMID:26624591

  7. Ionizing radiation promotes advanced malignant traits in nasopharyngeal carcinoma via activation of epithelial-mesenchymal transition and the cancer stem cell phenotype

    PubMed Central

    SU, ZHONGWU; LI, GUO; LIU, CHAO; REN, SHULING; TIAN, YONGQUAN; LIU, YONG; QIU, YUANZHENG

    2016-01-01

    Post-irradiation residual mass and recurrence always suggest a worse prognosis for nasopharyngeal carcinoma (NPC). Our study aimed to investigate the malignant behaviors of post-irradiation residual NPC cells, to identify the potential underlying mechanisms and to search for appropriate bio-targets to overcome this malignancy. Two NPC cell lines were firstly exposed to 60 Gy irradiation, and residual cells were collected. In our previous study, colony formation assay detected the radioresistance of these cells. Here, the CCK-8 assay examined the cell sensitivity to paclitaxel and cisplatin. Wound-healing and Transwell assays were performed to investigate cell motility and invasion capabilities. Inverted phase-contrast microscopy was used to observe and photograph the morphology of cells. Expression levels of epithelial-mesenchymal transition (EMT)-related proteins were detected by western blot assay in NPC cells and tissues. The mRNA levels of cancer stem cell (CSC)-related genes were detected via qRT-PCR. The results revealed that residual NPC cells exhibited enhanced radioresistance and cross-resistance to paclitaxel and cisplatin. Higher capacities of invasion and migration were also observed. An elongated morphology with pseudopodia formation and broadening in the intercellular space was observed in the residual cells. Downregulation of E-cadherin and upregulation of vimentin were detected in the residual NPC cells and tissues. CSC-related Lgr5 and c-myc were significantly upregulated in the CNE-2-Rs and 6-10B-Rs radioresistance cells. Higher proportions of Lgr5+ cells were observed in radioresistant cells via immunofluorescent staining and flow cytometry. In conclusion, our study demonstrated that residual NPC cells had an advanced malignant transition and presented with both EMT and a CSC phenotype. This provides a possible clue and treatment strategy for advanced and residual NPC. PMID:27108809

  8. Phase I/II Study of Erlotinib Combined With Cisplatin and Radiotherapy in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck

    SciTech Connect

    Herchenhorn, Daniel; Dias, Fernando L.; Viegas, Celia M.P.; Federico, Miriam H.; Araujo, Carlos Manoel M.; Small, Isabelle; Bezerra, Marcos; Fontao, Karina M.D.; Knust, Renata E.; Ferreira, Carlos G.; Martins, Renato G.

    2010-11-01

    Purpose: Erlotinib, an oral tyrosine kinase inhibitor, is active against head-and-neck squamous cell carcinoma (HNSCC) and possibly has a synergistic interaction with chemotherapy and radiotherapy. We investigated the safety and efficacy of erlotinib added to cisplatin and radiotherapy in locally advanced HNSCC. Methods and Materials: In this Phase I/II trial 100 mg/m{sup 2} of cisplatin was administered on Days 8, 29, and 50, and radiotherapy at 70 Gy was started on Day 8. During Phase I, the erlotinib dose was escalated (50 mg, 100 mg, and 150 mg) in consecutive cohorts of 3 patients, starting on Day 1 and continuing during radiotherapy. Dose-limiting toxicity was defined as any Grade 4 event requiring radiotherapy interruptions. Phase II was initiated 8 weeks after the last Phase I enrollment. Results: The study accrued 9 patients in Phase I and 28 in Phase II; all were evaluable for efficacy and safety. No dose-limiting toxicity occurred in Phase I, and the recommended Phase II dose was 150 mg. The most frequent nonhematologic toxicities were nausea/vomiting, dysphagia, stomatitis, xerostomia and in-field dermatitis, acneiform rash, and diarrhea. Of the 31 patients receiving a 150-mg daily dose of erlotinib, 23 (74%; 95% confidence interval, 56.8%-86.3%) had a complete response, 3 were disease free after salvage surgery, 4 had inoperable residual disease, and 1 died of sepsis during treatment. With a median 37 months' follow-up, the 3-year progression-free and overall survival rates were 61% and 72%, respectively. Conclusions: This combination appears safe, has encouraging activity, and deserves further studies in locally advanced HNSCC.

  9. Subsite, T Class, and N Class Cannot be Used to Exclude the Retropharyngeal Nodes From Treatment De-Intensification in Advanced Oropharyngeal Squamous Cell Carcinoma

    PubMed Central

    Spector, Matthew E.; Chinn, Steven B.; Bellile, Emily; Gallagher, K. Kelly; Kang, Stephen Y.; Moyer, Jeffrey S.; Prince, Mark E.; Wolf, Gregory T.; Bradford, Carol R.; McHugh, Jonathan B.; Carey, Thomas E.; Worden, Francis P.; Eisbruch, Avraham; Ibrahim, Mohannad; Chepeha, Douglas B.

    2016-01-01

    Importance Understanding the drainage patterns to the retropharyngeal nodes is an important consideration in oropharyngeal squamous cell carcinoma (OPSCC) because treatment of these nodes is related to increased morbidity. Prediction of these drainage patterns could not only help minimize treatment morbidity, but could also prevent failures in at-risk patients, as de-escalation trials are underway for this disease. Objective To evaluate the prevalence of pathologic retropharyngeal adenopathy (RPA) in OPSCC relative to involvement of the oropharyngeal subsite, number of neck nodes, T classification and N classification. Design Retrospective review from 2003–2010 Setting Academic Referral Center Participants 205 previously untreated, advanced stage (III, IV), pathologically confirmed patients with OPSCC Exposure: Concurrent chemoradiation Main Outcome Measures Radiologic evidence of pathologic RPA was tabulated and related to involvement of the oropharyngeal subsite, number of neck nodes, T classification and N classification. Results Pathologic RPA was identified in 18% of patients. There were pathologic retropharyngeal lymph nodes in 12/89 (13%) base of tongue cancers, 24/109 (22%) tonsil cancers, and 1/7 (14%) other oropharyngeal subsite cancers. Increasing prevalence of RPA was positively correlated with closer proximity to the posterior tonsillar pillar. A multivariate predictive regression model using the oropharyngeal subsite, involvement of the posterior tonsillar pillar, number of metastatic nodes, T classification, and N classification, showed that the number of metastatic nodes was statistically significant with an odds ratio of 1.436 (p=0.0001, 95% confidence interval: 1.203 – 1.714). Conclusions and Relevance The prevalence of pathologic RPA in this cohort was 18% and patients with multiple nodes had the highest risk for pathologic RPA, followed by involvement of the posterior tonsillar pillar. However, this data suggests that there is no clear

  10. Monitoring of Circulating Tumor Cells and Their Expression of EGFR/Phospho-EGFR During Combined Radiotherapy Regimens in Locally Advanced Squamous Cell Carcinoma of the Head and Neck

    SciTech Connect

    Tinhofer, Ingeborg; Hristozova, Tsvetana; Stromberger, Carmen; KeilhoIz, Ulrich; Budach, Volker

    2012-08-01

    Purpose: The numbers of circulating tumor cells (CTCs) and their expression/activation of epidermal growth factor receptor (EGFR) during the course of combined chemo- or bioradiotherapy regimens as potential biomarkers of treatment efficacy in squamous cell carcinoma of the head and neck (SCCHN) were determined. Methods and Materials: Peripheral blood samples from SCCHN patients with locally advanced stage IVA/B disease who were treated with concurrent radiochemotherapy or induction chemotherapy followed by bioradiation with cetuximab were included in this study. Using flow cytometry, the absolute number of CTCs per defined blood volume as well as their expression of EGFR and its phosphorylated form (pEGFR) during the course of treatment were assessed. Results: Before treatment, we detected {>=}1 CTC per 3.75 mL blood in 9 of 31 patients (29%). Basal expression of EGFR was detected in 100% and pEGFR in 55% of the CTC+ cases. The frequency of CTC detection was not influenced by induction chemotherapy. However, the number of CTC+ samples significantly increased after radiotherapy. This radiation-induced increase in CTC numbers was less pronounced when radiotherapy was combined with cetuximab compared to its combination with cisplatin/5-fluorouracil. The former treatment regimen was also more effective in reducing pEGFR expression in CTCs. Conclusions: Definitive radiotherapy regimens of locally advanced SCCHN can increase the number of CTCs and might thus contribute to a systemic spread of tumor cells. Further studies are needed to evaluate the predictive value of the radiation-induced increase in CTC numbers and the persistent activation of the EGFR signalling pathway in individual CTC+ cases.

  11. Concurrent Chemo-Radiation With or Without Induction Gemcitabine, Carboplatin, and Paclitaxel: A Randomized, Phase 2/3 Trial in Locally Advanced Nasopharyngeal Carcinoma

    SciTech Connect

    Tan, Terence; Lim, Wan-Teck; Fong, Kam-Weng; Cheah, Shie-Lee; Soong, Yoke-Lim; Ang, Mei-Kim; Ng, Quan-Sing; Tan, Daniel; Ong, Whee-Sze; Tan, Sze-Huey; Yip, Connie; Quah, Daniel; Soo, Khee-Chee; Wee, Joseph

    2015-04-01

    Purpose: To compare survival, tumor control, toxicities, and quality of life of patients with locally advanced nasopharyngeal carcinoma (NPC) treated with induction chemotherapy and concurrent chemo-radiation (CCRT), against CCRT alone. Patients and Methods: Patients were stratified by N stage and randomized to induction GCP (3 cycles of gemcitabine 1000 mg/m{sup 2}, carboplatin area under the concentration-time-curve 2.5, and paclitaxel 70 mg/m{sup 2} given days 1 and 8 every 21 days) followed by CCRT (radiation therapy 69.96 Gy with weekly cisplatin 40 mg/m{sup 2}), or CCRT alone. The accrual of 172 was planned to detect a 15% difference in 5-year overall survival (OS) with a 5% significance level and 80% power. Results: Between September 2004 and August 2012, 180 patients were accrued, and 172 (GCP 86, control 86) were analyzed by intention to treat. There was no significant difference in OS (3-year OS 94.3% [GCP] vs 92.3% [control]; hazard ratio 1.05; 1-sided P=.494]), disease-free survival (hazard ratio 0.77, 95% confidence interval 0.44-1.35, P=.362), and distant metastases–free survival (hazard ratio 0.80, 95% confidence interval 0.38-1.67, P=.547) between the 2 arms. Treatment compliance in the induction phase was good, but the relative dose intensity for concurrent cisplatin was significantly lower in the GCP arm. Overall, the GCP arm had higher rates of grades 3 and 4 leukopenia (52% vs 37%) and neutropenia (24% vs 12%), but grade 3 and 4 acute radiation toxicities were not statistically different between the 2 arms. The global quality of life scores were comparable in both arms. Conclusion: Induction chemotherapy with GCP before concurrent chemo-irradiation did not improve survival in locally advanced NPC.

  12. Preliminary efficacy, safety, pharmacokinetics, pharmacodynamics and quality of life study of pegylated recombinant human arginase 1 in patients with advanced hepatocellular carcinoma.

    PubMed

    Yau, Thomas; Cheng, Paul N; Chan, Pierre; Chen, Li; Yuen, Jimmy; Pang, Roberta; Fan, Sheung Tat; Wheatley, Denys N; Poon, Ronnie T

    2015-04-01

    This study was designed to evaluate the efficacy, safety profile, pharmacokinetics, pharmacodynamics and quality of life of pegylated recombinant human arginase 1 (Peg-rhAgr1) in patients with advanced hepatocellular carcinoma (HCC). Patients were given weekly doses of Peg-rhAgr1 (1600 U/kg). Tumour response was assessed every 8 weeks using RECIST 1.1 and modified RECIST criteria. A total of 20 patients were recruited, of whom 15 were deemed evaluable for treatment efficacy. Eighteen patients (90%) were hepatitis B carriers. Median age was 61.5 (range 30-75). Overall disease control rate was 13%, with 2 of the 15 patients achieving stable disease for >8 weeks. The median progression-free survival (PFS) was 1.7 (95% CI: 1.67-1.73) months, with median overall survival (OS) of all 20 enrolled patients being 5.2 (95% CI: 3.3-12.0) months. PFS was significantly prolonged in patients with adequate arginine depletion (ADD) >2 months versus those who had ≤2 months of ADD (6.4 versus 1.7 months; p = 0.01). The majority of adverse events (AEs) were grade 1/2 non-hematological toxicities. Transient liver dysfunctions (25%) were the most commonly reported serious AEs and likely due to disease progression. Pharmacokinetic and pharmacodynamic data showed that Peg-rhAgr1 induced rapid and sustained arginine depletion. The overall quality of life of the enrolled patients was well preserved. Peg-rhAgr1 is well tolerated with a good toxicity profile in patients with advanced HCC. A weekly dose of 1600 U/kg is sufficient to induce ADD. Significantly longer PFS times were recorded for patients who had ADD for >2 months.

  13. SU-E-T-275: Radiobiological Evaluation of Intensity Modulated Radiotherapy Treatment for Locally Advanced Head and Neck Squamous Cell Carcinomas

    SciTech Connect

    Rekha Reddy, B.; Ravikumar, M.; Tanvir Pasha, C.R; Anil Kumar, M.R; Varatharaj, C.; Pyakuryal, A; Narayanasamy, Ganesh

    2014-06-01

    Purpose: To evaluate the radiobiological outcome of Intensity Modulated Radiotherapy Treatment (IMRT) for locally advanced head and neck squamous cell carcinomas using HART (Histogram Analysis in Radiation Therapy; J Appl Clin Med Phys 11(1): 137–157, 2010) program and compare with the clinical outcomes. Methods: We have treated 20 patients of stage III and IV HNSCC Oropharynx and hypopharynx with accelerated IMRT technique and concurrent chemotherapy. Delineation of tumor and normal tissues were done using Danish Head and Neck Cancer Group (DAHANCA) contouring guidelines and radiotherapy was delivered to a dose of 70Gy in 35 fractions to the primary and involved lymph nodes, 63Gy to intermediate risk areas and 56 Gy to lower risk areas, Monday to Saturday, 6 Days/week using 6 MV Photons with an expected overall treatment time of 6 weeks. The TCP and NTCP's were calculated from the dose-volume histogram (DVH) statistics using the Poisson Statistics (PS) and JT Lyman models respectively and the Resultwas correlated with clinical outcomes of the patients with mean follow up of 24 months. Results: Using HART program, the TCP (0.89± 0.01) of primary tumor and the NTCP for parotids (0.20±0.12), spinal cord (0.05±0.01), esophagus (0.30±0.2), mandible (0.35±0.21), Oral cavity (0.37±0.18), Larynx (0.30±0.15) were estimated and correlated with clinical outcome of the patients. Conclusion: Accelerated IMRT with Chemotherapy is a clinical feasible option in the treatment of locally advanced HNSCC with encouraging initial tumour response and acceptable acute toxicities. The correlation between the clinical outcomes and radiobiological model estimated parameters using HART programs are found to be satisfactory.

  14. Preliminary Results of a Prospective Randomized Trial Comparing Concurrent Chemoradiotherapy Plus Adjuvant Chemotherapy With Radiotherapy Alone in Patients With Locoregionally Advanced Nasopharyngeal Carcinoma in Endemic Regions of China

    SciTech Connect

    Chen Yong; Liu Mengzhong; Liang Shaobo; Zong Jingfeng; Mao Yanping; Tang Linglong; Guo Ying; Lin Aihua; Zeng Xiangfa; Ma Jun

    2008-08-01

    Purpose: A prospective randomized trial was performed to evaluate the efficacy of concurrent chemotherapy and adjuvant chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) in endemic regions of China. Methods and Materials: Between July 2002 and September 2005, 316 eligible patients were randomly assigned to receive either radiotherapy alone (RT) or chemoradiotherapy concurrent with adjuvant chemotherapy (CRT). All patients received 70 Gy in 7 weeks using standard RT portals and techniques. The CRT patients were given concurrent cisplatin (40 mg/m{sup 2} on Day 1) weekly during RT, followed by cisplatin (80 mg/m{sup 2} on Day 1) and fluorouracil (800 mg/m{sup 2} on Days 1-5) every 4 weeks (Weeks 5, 9, and 13) for three cycles after completion of RT. All patients were analyzed by intent-to-treat analysis. Results: The two groups were well-balanced in all prognostic factors and RT parameters. The CRT group experienced significantly more acute toxicity (62.6% vs. 32%, p = 0.000). A total of 107 patients (68%) and 97 patients (61%) completed all cycles of concurrent chemotherapy and adjuvant chemotherapy, with a median follow-up time of 29 months. The 2-year overall survival rate, failure-free survival rate, distant failure-free survival rate, and locoregional failure-free survival rate for the CRT and RT groups were 89.8% vs. 79.7% (p = 0.003), 84.6% vs. 72.5% (p = 0.001), 86.5% vs. 78.7% (p = 0.024), and 98.0% vs. 91.9% (p = 0.007), respectively. Conclusions: This trial demonstrated the significant survival benefits of concurrent chemotherapy plus adjuvant chemotherapy in patients with locoregionally advanced NPC in endemic regions of China.

  15. Comparison of the short-term efficacy between docetaxel plus carboplatin and 5-fluorouracil plus carboplatin in locoregionally advanced nasopharyngeal carcinoma

    PubMed Central

    Lv, Xing; Xia, Wei-Xiong; Ke, Liang-Ru; Yang, Jing; Qiu, Wen-Zhe; Yu, Ya-Hui; Liang, Hu; Huang, Xin-Jun; Liu, Guo-Yin; Zeng, Qi; Guo, Xiang; Xiang, Yan-Qun

    2016-01-01

    Objective Platinum-based chemotherapy in combination with radiotherapy is a standard treatment strategy for locoregionally advanced nasopharyngeal carcinoma (NPC). This study aimed to investigate the long-term efficacy and tolerability of inductive chemotherapy with docetaxel plus carboplatin (TC) or 5-fluorouracil plus carboplatin (FC) followed by concurrent radiation therapy in patients with NPC. Methods Patients (N=88) were randomized to receive TC or FC as inductive therapy followed by concurrent radiotherapy (60–70 Gy) with two cycles of carboplatin (area under the curve =5 mg·h/L). Patients were followed up for 8 years. Primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), toxicity, tumor response, distant metastasis-free survival, and local recurrence-free survival. Results At the end of the follow-up period, 31 patients died, 32 had disease progression, eleven had cancer recurrence, and 25 had distant metastasis. Overall, there was no difference between treatment groups with regard to response or survival. We found that following induction and concurrent chemoradiotherapy, the majority of patients showed a complete response (~96%–98% for induction therapy and 82%–84% for comprehensive therapy) to both therapies. PFS and OS were also similar between groups. The rate of PFS was 63.6% for both FC and TC and that of OS was 65.9% and 63.5%, respectively. The overall incidence of grade 3–4 adverse events in the TC group (20.5%) was higher than in the FC group (10.7%). Neutropenia and leukopenia were the most common grade 3–4 adverse events in the TC group, and mucositis was the most common in the FC group. Conclusion These data indicate that TC and FC therapies have similar efficacy in treating locally advanced NPC and both are well tolerated. PMID:27574453

  16. Significantly greater expression of ER, PR, and ECAD in advanced-stage low-grade ovarian serous carcinoma as revealed by immunohistochemical analysis.

    PubMed

    Wong, Kwong-Kwok; Lu, Karen H; Malpica, Anais; Bodurka, Diane C; Shvartsman, Hyun S; Schmandt, Rosemarie E; Thornton, Angela D; Deavers, Michael T; Silva, Elvio G; Gershenson, David M

    2007-10-01

    A 2-tier system that classifies ovarian serous carcinoma (OSC) as low grade or high grade is gaining acceptance. Women with low-grade OSC generally have higher 5-year survival rates than do women with high-grade OSC. We examined the expression of various markers to further understand the molecular differences between low-grade and high-grade OSCs: the potential therapeutic targets or prognostic markers Her-2/neu, estrogen receptor, and progesterone receptor (PR); the metastasis-associated markers cyclin D1 (BCL1), E-cadherin, matrix metalloproteinase (MMP) 2, and MMP-9; and the cell proliferation-associated markers BCL1, Ki-67 antigen (Ki-67), and p53. For this immunohistochemical analysis, we used paraffin-embedded specimens from 47 patients with advanced-stage low-grade OSC and from 49 patients with advanced-stage high-grade OSC. Our results showed that low-grade tumors expressed significantly higher levels of estrogen receptor, PR, and E-cadherin than did high-grade tumors, suggesting the involvement of gonadal steroid hormones, especially in the pathogenesis of low-grade OSC; the PR positivity was also observed in the stromal component of these low-grade tumors. On the other hand, high-grade tumors trended toward increased expression of MMP-9, BCL1, p53, and Ki-67, and robust MMP-9 positivity was observed in the stromal component of these high-grade tumors. These differences may lead to the development of different therapeutic strategies for women with either the low-grade or the high-grade form of OSC.

  17. Rapid and early α-fetoprotein and des-γ-carboxy prothrombin responses to initial arterial infusion chemotherapy predict treatment outcomes of advanced hepatocellular carcinoma

    PubMed Central

    OYAMA, KENJI; KODA, MASAHIKO; SUGIHARA, TAKAAKI; KISHINA, MANABU; MIYOSHI, KENICHI; OKAMOTO, TOSHIAKI; HODOTSUKA, MASANORI; FUJISE, YUKI; MATONO, TOMOMITSU; TOKUNAGA, SHIHO; OKAMOTO, KINYA; HOSHO, KEIKO; OKANO, JUNICHI; MURAWAKI, YOSHIKAZU

    2015-01-01

    The aim of the present study was to predict the effects of transarterial infusion (TAI) chemotherapy based on early changes in α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) in patients with advanced hepatocellular carcinoma (HCC). Seventy-four patients who underwent TAI with cisplatin, 5-fluorouracil, mitomycin C and epirubicin for advanced HCC were enrolled. Antitumor responses were evaluated 6 months after TAI. Rapid and early responses were defined as the ratio of AFP or DCP after 1 week and 1 month compared to baseline. A total of 5, 10, 17 and 42 patients had complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD), respectively. Early AFP response was significantly lower in the CR+PR compared to the SD+PD groups (P<0.01). The early DCP response was significantly lower in the CR+PR compared to the SD+PD. The sensitivity and specificity of rapid and early AFP responses in the CR+PR were 0.78 and 0.72, and 0.80 and 0.73, respectively, and those of rapid and early DCP responses were 0.67 and 0.65, and 0.77 and 0.71, respectively. The combination of AFP and DCP responses had higher specificity compared to AFP or DCP alone responses. Patients were divided into responder and non-responder groups to evaluate the prediction of survival outcome. Early responders of AFP, DCP and AFP+DCP, who were divided based on the cut-off values of CR+PR survived significantly longer than the non-responders (P<0.05). In conclusion, rapid or early responses of AFP and/or DCP levels 1 and 4 weeks after TAI chemotherapy helped to predict the treatment effects. PMID:26137283

  18. [Concomitant radiochemotherapy in cancer of the cervix uteri: modifications of the standards].

    PubMed

    Haie-Meder, C; Lhommé, C; de Crevoisier, R; Morice, P; Resbeut, M

    2000-11-01

    For a long time, combined external irradiation and brachytherapy has been considered as the standard treatment in patients with advanced cervical cancers. Recently, five clinical randomized trials assessing the role of cis-platin-based chemotherapy delivered concomitantly to radiotherapy have been conducted in the United States. Another clinical randomized trial assessing the role of epirubicin was conducted by the Queen Mary Hospital in Hong Kong. With more than 2,000 enrolled patients, these studies showed converging results with an overall and disease-free survival improvement in the arms combining cis-platin and epirubicin-based chemotherapy and irradiation. These combinations led to a significant decrease in loco-regional evolution or recurrence rates, or even in pulmonary metastases rates. The relative risk of recurrences was decreased by 50%. The relative risk of death was decreased by 40%. The differences, however, were less significant in patients with advanced stages III or IVA. Hematological and digestive acute toxicity was significantly higher in the radiochemotherapy groups, but long-term complications were comparable. The results of these randomized trials have led to a modification in the standard of treatment in these poor prognosis cervix cancers. Five of the randomized trials evidenced the superiority of cis-platin-based chemotherapy, but the optimal chemotherapeutic regimens remain to be defined.

  19. A single arm phase 1b study of everolimus and sunitinib in patients with advanced renal cell carcinoma (RCC)

    PubMed Central

    Kanesvaran, R.; Watt, K.; Turnbull, J. D.; Armstrong, A. J.; Cohen-Wolkowiez, M.; George, D. J.

    2016-01-01

    Background Everolimus ,an oral inhibitor of mammalian target of rapamycin (mTOR), and sunitinib, an oral inhibitor of VEGF/PDGF receptor tyrosine kinase signaling, have both been shown to provide clinical benefit in patients with advanced RCC. We sought to determine the safety and efficacy of combination therapy with these agents in patients with advanced RCC. Methods We conducted a phase Ib dose escalation trial of sunitinib and everolimus in patients with advanced metastatic RCC. Prior nephrectomy was required, and prior radiation or chemotherapy other than VEGF/mTOR-based therapies was permitted. The primary endpoint was to determine the MTD/recommended phase 2 dose. Results A total of 4 out of a planned 30 subjects were enrolled in this study (M:F= 2:2; mean age 52 years, 50% with KPS <80). The first three patients were enrolled on a 4+2 dosing schedule of daily sunitinib 50 mg and weekly everolimus 30 mg. Mean time on drug was 99 days. One partial response was seen. Toxicities included mucositis, thrombocytopenia, anemia, fatigue, dehydration and hypoglycemia. Due to multiple grade 3–4 toxicities, the protocol was amended to 2+1 dosing of sunitinib 37.5 mg and daily everolimus 5mg. The first patient on this schedule died from multi-organ failure with septic shock after 1 cycle of treatment. Subsequently, the study was closed. Pharmacokinetics results inconclusively suggest that toxicities could be attributed to the drug exposure. Conclusions Combined use of everolimus and sunitinib in the treatment of mRCC was not well tolerated in this small cohort. PMID:26174223

  20. Physical considerations in the treatment of advanced carcinomas of the larynx and pyriform sinuses using 10 MV x rays

    SciTech Connect

    Doppke, K.; Novack, D.; Wang, C.C.

    1980-09-01

    A technique for treating patients who have advanced tumors of the larynx and pyriform sinus was developed using isocentric anterior and posterior opposed fields with 10 MV x rays. This technique can be used to deliver a tumor dose of 45 Gray to the primary site and regional nodes and approximately 40 Gray to the spinal cord. The method eliminates problems of multi-field junctures and lowers the daily spinal cord dose when compared to the standard parallel opposed lateral portals and anterior neck fields.

  1. The comparison of plasma D-dimer levels in benign and malignant tumors of cervix, ovary and uterus

    PubMed Central

    Vahid Dastjerdi, Marzieh; Ahmari, Soraya; Alipour, Sadaf; Tehranian, Afsaneh

    2015-01-01

    Background: Thromboembolism is the most important complication of cancers.The aim of this study was to determine D-dimer levels in benign and malignant tumors of the uterus, ovary and cervix. Subjects and Methods: This was a cross sectional study and it was conducted on 90 female patients referred to Imam Khomeini and Arash Hospitals because of uterine, cervical and ovarian tumors in 2013-2014. After surgical resection or tissue biopsy, 2 cc of each patient’s blood was taken to be sent to laboratory of hospitals. “Nycocard” kit was chosen to measure D-dimer levels in Mg/Lit by neflumetry method. Data were analyzed in SPSS-16 by T-test and One-Way ANOVA test. Results: The highest mean of D-dimer was 3.9 (± 2.9SD) in malignant cervical tumors. The mean plasma levels of D-dimer in malignant uterine cancers (P = 0.008), ovarian cancers (P = 0.007) and cervical cancers (P = 0.006) was significantly higher than benign tumors. In all three types of uterine, ovarian and cervical cancers, D-dimer was significantly higher in advanced stages than lower stages. Conclusion: The plasma D-dimer levels in patients with malignant tumors of the uterus, cervix and ovary were higher than benign types. By increasing the stage of gynecologic malignant tumors, the levels of plasma D-dimer were increased. PMID:26261694

  2. Continuous infusion cisplatin and 5-fluorouracil with bolus vinorelbine in the treatment of advanced nonsmall cell carcinoma of the lung.

    PubMed

    Beuzeboc, P; Livartowski, A; Dierick, A; Paraiso, D; Pouillart, P

    1995-01-01

    Thirty-three patients, with histologically proven advanced nonsmall cell lung cancer (NSCLC) were treated at Institut Curie with a three-drug combination chemotherapy. The regimen consisted of cisplatin 25 mg/m2 per day continuous infusion (CI) and 5-fluorouracil (5-FU) CI 600 mg/m2 on 5 consecutive days with 30 minutes infusion navelbine 25 mg/m2 on days 1 and 5 only. Cycles were repeated every 28 days. Response was evaluated after three cycles. One patient died of an ischemic cerebrovascular stroke after the third cycle. Thirty-two pts were evaluable. Partial response was achieved in 11/20 patients with stage III disease (55%) and in 7/12 patients with stage IV disease (58%). WHO grade 4 toxicities were leucopenia 31%, thrombocytopenia 4%, and mucositis 4%. The tolerance was acceptable. Median survival was 19 months for stage III and 9.5 months for stage IV. We conclude that the combination of 5-FU, navelbine, and cisplatin is an effective chemotherapy regimen for patients with advanced stage NSCLC.

  3. Curative-Intent Aggressive Treatment Improves Survival in Elderly Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma and High Comorbidity Index

    PubMed Central

    Chen, Jin-Hua; Yen, Yu-Chun; Yang, Hsuan-Chia; Liu, Shing-Hwa; Yuan, Sheng-Po; Wu, Li-Li; Lee, Fei-Peng; Lin, Kuan-Chou; Lai, Ming-Tang; Wu, Chia-Che; Chen, Tsung-Ming; Chang, Chia-Lun; Chow, Jyh-Ming; Ding, Yi-Fang; Wu, Szu-Yuan

    2016-01-01

    Abstract For locally advanced head and neck squamous cell carcinoma (HNSCC), therapeutic decisions depend on comorbidity or age. We estimated the treatment outcomes of patients with different Charlson comorbidity index (CCI) scores and ages to determine whether aggressive treatment improves survival. Data from the Taiwan National Health Insurance and cancer registry databases were analyzed, and we included >20-year-old patients with American Joint Committee on Cancer (AJCC) stage III or IV HNSCC (International Classification of Diseases, Ninth Revision, Clinical Modification codes 140.0–148.9) undergoing surgery, chemotherapy (CT), radiotherapy (RT), concurrent chemoradiotherapy (CCRT), sequential CT and RT, or surgery with adjuvant treatment. The exclusion criteria were a past cancer history, distant metastasis, AJCC stage I or II, missing sex data, an age < 20 years, nasopharyngeal cancer, in situ carcinoma, sarcoma, and HNSCC recurrence. The index date was the date of first HNSCC diagnosis, and comorbidities were scored using the CCI. The enrolled patients were categorized into Group 1 (curative-intent aggressive treatments) and Group 2 (best supportive care or palliative treatments). We enrolled 21,174 stage III or IV HNSCC patients without distant metastasis (median follow-up, 3.25 years). Groups 1 and 2 comprised 18,584 and 2232 patients, respectively. After adjustment for age, sex, and clinical stage, adjusted hazard ratios (95% confidence intervals) of overall death in Group 1 were 0.33 (0.31–0.35), 0.34 (0.31–0.36), and 0.37 (0.28–0.49), and those of all-cause death among patients undergoing curative surgical aggressive treatments were 1.13 (0.82–1.55), 0.67 (0.62–0.73), and 0.49 (0.46–0.53) for CCI scores of ≥10, 5 to 9, and <5, respectively. Aggressive treatments improve survival in elderly (≥65 years) and critically ill HNSCC patients. Curative nonsurgical aggressive treatments including definitive RT or CCRT might be suitable for

  4. Curative-Intent Aggressive Treatment Improves Survival in Elderly Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma and High Comorbidity Index.

    PubMed

    Chen, Jin-Hua; Yen, Yu-Chun; Yang, Hsuan-Chia; Liu, Shing-Hwa; Yuan, Sheng-Po; Wu, Li-Li; Lee, Fei-Peng; Lin, Kuan-Chou; Lai, Ming-Tang; Wu, Chia-Che; Chen, Tsung-Ming; Chang, Chia-Lun; Chow, Jyh-Ming; Ding, Yi-Fang; Wu, Szu-Yuan

    2016-04-01

    For locally advanced head and neck squamous cell carcinoma (HNSCC), therapeutic decisions depend on comorbidity or age. We estimated the treatment outcomes of patients with different Charlson comorbidity index (CCI) scores and ages to determine whether aggressive treatment improves survival.Data from the Taiwan National Health Insurance and cancer registry databases were analyzed, and we included >20-year-old patients with American Joint Committee on Cancer (AJCC) stage III or IV HNSCC (International Classification of Diseases, Ninth Revision, Clinical Modification codes 140.0-148.9) undergoing surgery, chemotherapy (CT), radiotherapy (RT), concurrent chemoradiotherapy (CCRT), sequential CT and RT, or surgery with adjuvant treatment. The exclusion criteria were a past cancer history, distant metastasis, AJCC stage I or II, missing sex data, an age < 20 years, nasopharyngeal cancer, in situ carcinoma, sarcoma, and HNSCC recurrence. The index date was the date of first HNSCC diagnosis, and comorbidities were scored using the CCI. The enrolled patients were categorized into Group 1 (curative-intent aggressive treatments) and Group 2 (best supportive care or palliative treatments).We enrolled 21,174 stage III or IV HNSCC patients without distant metastasis (median follow-up, 3.25 years). Groups 1 and 2 comprised 18,584 and 2232 patients, respectively. After adjustment for age, sex, and clinical stage, adjusted hazard ratios (95% confidence intervals) of overall death in Group 1 were 0.33 (0.31-0.35), 0.34 (0.31-0.36), and 0.37 (0.28-0.49), and those of all-cause death among patients undergoing curative surgical aggressive treatments were 1.13 (0.82-1.55), 0.67 (0.62-0.73), and 0.49 (0.46-0.53) for CCI scores of ≥10, 5 to 9, and <5, respectively.Aggressive treatments improve survival in elderly (≥65 years) and critically ill HNSCC patients. Curative nonsurgical aggressive treatments including definitive RT or CCRT might be suitable for HNSCC patients with CCI scores

  5. Cervix Regression and Motion During the Course of External Beam Chemoradiation for Cervical Cancer

    SciTech Connect

    Beadle, Beth M.; Jhingran, Anuja; Salehpour, Mohammad; Sam, Marianne; Iyer, Revathy B.; Eifel, Patricia J.

    2009-01-01

    Purpose: To evaluate the magnitude of cervix regression and motion during external beam chemoradiation for cervical cancer. Methods and Materials: Sixteen patients with cervical cancer underwent computed tomography scanning before, weekly during, and after conventional chemoradiation. Cervix volumes were calculated to determine the extent of cervix regression. Changes in the center of mass and perimeter of the cervix between scans were used to determine the magnitude of cervix motion. Maximum cervix position changes were calculated for each patient, and mean maximum changes were calculated for the group. Results: Mean cervical volumes before and after 45 Gy of external beam irradiation were 97.0 and 31.9 cc, respectively; mean volume reduction was 62.3%. Mean maximum changes in the center of mass of the cervix were 2.1, 1.6, and 0.82 cm in the superior-inferior, anterior-posterior, and right-left lateral dimensions, respectively. Mean maximum changes in the perimeter of the cervix were 2.3 and 1.3 cm in the superior and inferior, 1.7 and 1.8 cm in the anterior and posterior, and 0.76 and 0.94 cm in the right and left lateral directions, respectively. Conclusions: Cervix regression and internal organ motion contribute to marked interfraction variations in the intrapelvic position of the cervical target in patients receiving chemoradiation for cervical cancer. Failure to take these variations into account during the application of highly conformal external beam radiation techniques poses a theoretical risk of underdosing the target or overdosing adjacent critical structures.

  6. Simultaneous Integrated Boost–Intensity Modulated Radiation Therapy With Concomitant Capecitabine and Mitomycin C for Locally Advanced Anal Carcinoma: A Phase 1 Study

    SciTech Connect

    Deenen, Maarten J.; Dewit, Luc; Boot, Henk; Beijnen, Jos H.; Schellens, Jan H.M.; Cats, Annemieke

    2013-04-01

    Purpose: Newer radiation techniques, and the application of continuous 5-FU exposure during radiation therapy using oral capecitabine may improve the treatment of anal cancer. This phase 1, dose-finding study assessed the feasibility and efficacy of simultaneous integrated boost–intensity modulated radiation therapy (SIB-IMRT) with concomitant capecitabine and mitomycin C in locally advanced anal cancer, including pharmacokinetic and pharmacogenetic analyses. Methods and Materials: Patients with locally advanced anal carcinoma were treated with SIB-IMRT in 33 daily fractions of 1.8 Gy to the primary tumor and macroscopically involved lymph nodes and 33 fractions of 1.5 Gy electively to the bilateral iliac and inguinal lymph node areas. Patients received a sequential radiation boost dose of 3 × 1.8 Gy on macroscopic residual tumor if this was still present in week 5 of treatment. Mitomycin C 10 mg/m{sup 2} (maximum 15 mg) was administered intravenously on day 1, and capecitabine was given orally in a dose-escalated fashion (500-825 mg/m{sup 2} b.i.d.) on irradiation days, until dose-limiting toxicity emerged in ≥2 of maximally 6 patients. An additional 8 patients were treated at the maximum tolerated dose (MTD). Results: A total of 18 patients were included. The MTD of capecitabine was determined to be 825 mg/m{sup 2} b.i.d. The predominant acute grade ≥3 toxicities included radiation dermatitis (50%), fatigue (22%), and pain (6%). Fifteen patients (83% [95%-CI: 66%-101%]) achieved a complete response, and 3 (17%) patients a partial response. With a median follow-up of 28 months, none of the complete responders, and 2 partial responders had relapsed. Conclusions: SIB-IMRT with concomitant single dose mitomycin C and capecitabine 825 mg/m{sup 2} b.i.d. on irradiation days resulted in an acceptable safety profile, and proved to be a tolerable and effective treatment regimen for locally advanced anal cancer.

  7. Capecitabine (Xeloda) improves medical resource use compared with 5-fluorouracil plus leucovorin in a phase III trial conducted in patients with advanced colorectal carcinoma.

    PubMed

    Twelves, C; Boyer, M; Findlay, M; Cassidy, J; Weitzel, C; Barker, C; Osterwalder, B; Jamieson, C; Hieke, K

    2001-03-01

    Standard therapy for advanced or metastatic colorectal cancer consists of 5-fluorouracil plus leucovorin (5-FU/LV) administered intravenously (i.v.). Capecitabine (Xeloda), an oral fluoropyrimidine carbamate which is preferentially activated by thymidine phosphorylase in tumour cells, mimics continuous 5-FU and is a recently developed alternative to i.v. 5-FU/LV. The choice of oral rather than intravenous treatment may affect medical resource use because the two regimens do not require the same intensity of medical intervention for drug administration, and have different toxicity profiles. Here we examine medical resource use in the first-line treatment of colorectal cancer patients with capecitabine compared with those receiving the Mayo Clinic regimen of 5-FU/LV. In a prospective, randomised phase III clinical trial, 602 patients with advanced or metastatic colorectal cancer recruited from 59 centres worldwide were randomised to treatment with either capecitabine or the Mayo regimen of 5-FU/LV. In addition to clinical efficacy and safety endpoints, data were collected on hospital visits required for drug administration, hospital admissions, and drugs and unscheduled consultations with physicians required for the treatment of adverse events. Capecitabine treatment in comparison to 5-FU/LV in advanced colorectal carcinoma resulted in superior response rates (26.6% versus 17.9%, P=0.013) and improved safety including less stomatitis and myelosuppression. Capecitabine patients required substantially fewer hospital visits for drug administration than 5-FU/LV patients. Medical resource use analysis showed that patients treated with capecitabine spent fewer days in hospital for the management of treatment related adverse events than did patients treated with 5-FU/LV. In addition, capecitabine reduced the requirement for expensive drugs, in particular antimicrobials fluconazole and 5-HT3-antagonists to manage adverse events. As anticipated with an oral home-based therapy

  8. Hepatocellular carcinoma.

    PubMed

    Llovet, Josep M; Zucman-Rossi, Jessica; Pikarsky, Eli; Sangro, Bruno; Schwartz, Myron; Sherman, Morris; Gores, Gregory

    2016-01-01

    Liver cancer is the second leading cause of cancer-related deaths globally and has an incidence of approximately 850,000 new cases per year. Hepatocellular carcinoma (HCC) represents approximately 90% of all cases of primary liver cancer. The main risk factors for developing HCC are well known and include hepatitis B and C virus infection, alcohol intake and ingestion of the fungal metabolite aflatoxin B1. Additional risk factors such as non-alcoholic steatohepatitis are also emerging. Advances in the understanding of the molecular pathogenesis of HCC have led to identification of critical driver mutations; however, the most prevalent of these are not yet druggable targets. The molecular classification of HCC is not established, and the Barcelona Clinic Liver Cancer staging classification is the main clinical algorithm for the stratification of patients according to prognosis and treatment allocation. Surveillance programmes enable the detection of early-stage tumours that are amenable to curative therapies - resection, liver transplantation or local ablation. At more developed stages, only chemoembolization (for intermediate HCC) and sorafenib (for advanced HCC) have shown survival benefits. There are major unmet needs in HCC management that might be addressed through the discovery of new therapies and their combinations for use in the adjuvant setting and for intermediate- and advanced-stage disease. Moreover, biomarkers for therapy stratification, patient-tailored strategies targeting driver mutations and/or activating signalling cascades, and validated measurements of quality of life are needed. Recent failures in the testing of systemic drugs for intermediate and advanced stages have indicated a need to refine trial designs and to define novel approaches. PMID:27158749

  9. Automatic glare removal in reflectance imagery of the uterine cervix

    NASA Astrophysics Data System (ADS)

    Lange, Holger

    2005-04-01

    Colposcopy is a diagnostic method used to detect cancer precursors and cancer of the uterine cervix. Computer-Aided-Diagnosis (CAD) for colposcopy is a new field in medical image processing. Colposcopists analyze glare (glint or specular reflection) patterns on the cervix to assess the surface contour (3D topology) of lesions, an important feature used to evaluate lesion severity. However, glare in the imagery presents major problems for automated image analysis systems. Glare eliminates all information in affected pixels and can introduce artifacts in feature extraction algorithms, such as acetowhite region detection. Although cross-polarization filters can be used to eliminate glare, the reality is that we have to deal with glare when we want to use existing cervical image databases or use an instrument that does not provide cross-polarized imagery. Here, we present the details and preliminary results of a glare removal algorithm for RGB color images of the cervix that can be used as a pre-processing step in CAD systems. The algorithm can be extended to multispectral and hyperspectral imagery. The basic approach of the algorithm is to extract a feature image from the RGB image that provides a good glare to background ratio, to detect the glare regions in the feature image, to extend the glare regions to cover all pixels that have been affected by the glare, and to remove the glare in the affected regions by filling in an estimate of the underlying image features. In our current implementation we use the green (G) image component as the feature image, given its high glare to background ratio and simplicity of calculation. Glare regions are either detected as saturated regions or small high contrasted bright regions. Saturated regions are detected using an adaptive thresholding method. Small high contrasted bright regions are detected using morphological top hat filters with different sizes and thresholds. The full extent of the glare regions is estimated by using

  10. Uterine Serous Adenocarcinoma in an Elderly Postmenopausal Woman: Clinically Misdiagnosed as Uterine Cervix Cancer

    PubMed Central

    Hong, Jeong-A; Lee, Hae-Hyeog; Chung, Soo-Ho; Heo, Gyeong-Eun; Jeon, Dong-Su; Kwak, Jeong Ja; Choi, Seung Do; Han, Eunkyung

    2015-01-01

    Uterine serous adenocarcinoma (USC) is rare and invasive cancer. This cancer is more often reported in the ovary, the fallopian tube, and the endometrium than uterine cervix. No matter where the tumor is located, the tumor exhibits similar histological characteristics. So when uterine cancer is proven to be serous adenocarcinoma, it is necessary to see if the tumor originated from ovary or endometrium and invaded the cervix. We report a case of a 73-year-old postmenopausal woman with USC arising near the internal os of endocervical canal, clinically misdiagnosed as uterine cervix cancer. PMID:26793684

  11. Image-Guided Radiotherapy for Cervix Cancer: High-Tech External Beam Therapy Versus High-Tech Brachytherapy

    SciTech Connect

    Georg, Dietmar Kirisits, Christian; Hillbrand, Martin; Dimopoulos, Johannes; Poetter, Richard

    2008-07-15

    Purpose: Many studies comparing external-beam therapy (EBT) and brachytherapy (BT) are biased because advanced EBT is compared with conventional BT. This study compares high-tech EBT against high-tech BT. Methods and Materials: Nine patients were selected with locally advanced cervix cancer, representing typical clinical situations according to initial tumor extension and response after EBT. Patients were treated either with intracavitary, combined interstitial/intracavitary, or complex interstitial BT. Gross tumor volume, high-risk clinical target volume (CTV), intermediate-risk CTV, bladder, rectum, and sigmoid were delineated. Magnetic resonance-guided BT planning was manually optimized with respect to organ dose limits. Margins (3 and 5 mm) were added to BT CTVs to construct planning target volumes (PTVs) for EBT. Inversely planned EBT with photons (IMRT) and protons (IMPT) was challenged to deliver the highest possible doses to PTVs while respecting D{sub 1cc} and D{sub 2cc} limits from BT, assuming the same fractionation (4 x 7 Gy). The D90 for target structures and normal tissue volumes receiving fractionated doses between 3 and 7 Gy were compared. Results: High-risk CTV doses depended on the clinical situation and radiation quality. If IMRT was limited to D{sub 2cc} and D{sub 1cc} from BT, the D90 for high-risk PTV and intermediate-risk PTV was mostly lower. Volumes receiving 60 Gy (in equivalent dose in 20 Gy fractions) were approximately twice as large for IMRT compared with BT. For IMPT, this volume ratio was lower. Planning target volume doses of IMPT plans with 3-mm margins were comparable to those with BT. Gross tumor volume doses were mostly lower for both IMRT and IMPT. Conclusion: For benchmarking high-tech EBT, high-tech BT techniques have to be used. For cervix cancer boost treatments, both IMRT and IMPT seem to be inferior to advanced BT.

  12. Hypofractionated Accelerated Radiotherapy With Concurrent Chemotherapy For Locally Advanced Squamous Cell Carcinoma of the Head and Neck

    SciTech Connect

    Sanghera, Paul; McConkey, Chris; Ho, Kean-Fatt; Glaholm, John; Hartley, Andrew . E-mail: andrew.hartley@uhb.nhs.uk

    2007-04-01

    Purpose: To investigate the tumor control rates in locally advanced head-and-neck cancer using accelerated hypofractionated radiotherapy with chemotherapy. Methods and Materials: The data from patients with squamous cell cancer of the larynx, oropharynx, oral cavity, and hypopharynx (International Union Against Cancer Stage II-IV), who received accelerated hypofractionated radiotherapy with chemotherapy between January 1, 1998, and April 1, 2005, were retrospectively analyzed. Two different chemotherapy schedules were used, carboplatin and methotrexate, both single agents administered on an outpatient basis. The endpoints were overall survival, local control, and disease-free survival. Results: A total of 81 patients were analyzed. The 2-year overall survival rate was 71.6% (95% confidence interval [CI], 61.5-81.8%). The 2-year disease-free survival rate was 68.6% (95% CI, 58.4-78.8%). The 2-year local control rate was 75.4% (95% CI, 65.6-85.1%). When excluding patients with Stage II oral cavity, larynx, and hypopharynx tumors, 68 patients remained. For these patients, the 2-year overall survival, local control, and disease-free survival rate was 67.6% (95% CI, 56.0-79.2%), 72.0% (95% CI, 61.0-83.0%), and 64.1% (95% CI, 52.6-75.7%), respectively. Conclusion: Accelerated hypofractionated radiotherapy and synchronous chemotherapy can achieve high tumor control rates while being resource sparing and should be the subject of prospective evaluation.

  13. [Post-radiation pelvic disease and ureteral stenosis: physiopathology and evolution in the patient treated for cervical carcinoma. Review of the literature and experience of the Radium Institute].

    PubMed

    Buglione, Michela; Toninelli, Mariasole; Pietta, Nicoletta; Ambrosi, Enrica; Filippini, Marzia; De Stefani, Agostina; Vitali, Elisabetta; De Tomasi, Dolores; Bertoni, Filippo; Caraffini, Bruno; Magrini, Stefano M

    2002-03-01

    Ureteral stenosis secondary to radiation-induced fibrosis is a well-known, late complication of radiation treatment in patients with carcinoma of the uterine cervix. This paper focuses on epidemiological data, physiopathology and treatment modalities reviewed from Internet-published literature. Experience from a single institution (Institute of Radiotherapy of Brescia) is reported. Ureteral stenosis has an incidence of 15% in patients treated with standard doses of radiotherapy for carcinoma of the uterine cervix. An asymptomatic low-grade fibrotic ureteral stenosis establishes at doses of 20 Gy in experimental animal models, and both incidence and severity rise with increasing of doses. An emerging role for Transforming Growth Factor beta 1 (TGF-beta 1) is recognized in determining chronic activation of fibroblast/fibrocyte lineage and remodelling extracellular matrix which are known mechanisms in the genesis of any fibrotic disease. Experience of the radiotherapy Institute of Brescia, Italy, is reported. A series of 191 patients with stage IB-IIA cervix carcinoma was treated with radical radiotherapy. About 10% of patients developed late urinary tract complications related to post-actinic fibrosis with only 1% of grade III-IV ureteral fibrosis. These data are consistent with those published by other institutions. In conclusion, late ureteral fibrosis is a common and distressing treatment-related complication in patients treated with radiotherapy for cervix carcinoma. Newer strategies in better defining the target for radiotherapy, conformational radiotherapy and better understanding of biologic factors will contribute to further reducing the frequency of such a complication.

  14. Results of treatment of uterine cervix cancer by radiotherapy.

    PubMed

    Sinistrero, G; Sismondi, P; Zola, P

    1988-12-01

    The results of treatment of uterine cervix cancer by radiotherapy alone in 259 patients in the period January 1973 to December 1984 are reported. They are analyzed according to patients age, stage, tumor volume, extent of parametrial infiltration, hydronephrosis and nodal status. It is shown that age, tumor volume, extent of parametrial invasion and nodal metastases are the main prognostic factors. Analysis of pelvic failures shows that external radiotherapy followed by curietherapy seems to be the best method for patients with T2b and T3b tumors of small volume (less than 60 mm in diameter), particularly when parametrial infiltration is limited. Patients with T2b tumors of large volume (barrel shaped) seem to need a more aggressive approach, and a higher number of complications are therefore expected. Patients with T3b and massive parametrial infiltration, with T4 and nodal metastases need new and different approaches, possibly including adjuvant chemotherapy.

  15. Pazopanib for the first-line treatment of patients with advanced and/or metastatic renal cell carcinoma : a NICE single technology appraisal.

    PubMed

    Kilonzo, Mary; Hislop, Jenni; Elders, Andrew; Fraser, Cynthia; Bissett, Donald; McClinton, Samuel; Mowatt, Graham; Vale, Luke

    2013-01-01

    The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of pazopanib hydrochloride (GlaxoSmithKline) to submit evidence of the clinical and cost effectiveness of the drug for the first-line treatment of advanced and/or metastatic renal cell carcinoma, as part of the Institute's single technology appraisal (STA) process. The Aberdeen Health Technology Assessment Group were commissioned to act as the Evidence Review Group (ERG). This article provides a description of the company submission, the ERG review and NICE's subsequent decisions. The objective of this paper is to summarize the independent review and critique of the evidence submitted for the consideration of the NICE Appraisal Committee and NICE's subsequently issued guidance. The ERG produced a critical review of the evidence for the clinical and cost effectiveness of the technology based upon the manufacturer's submission to NICE. The ERG also independently searched for relevant evidence and modified the manufacturer's decision analytic model to examine the impact of altering some of the key assumptions. For progression-free survival (PFS), there was a statistically significant longer survival for pazopanib compared with placebo (as assessed by the ERG, based upon the original manufacturer submission with a clinical cut-off date of 23 May 2008) [median 11.1 vs. 2.8 months; hazard ratio (HR) 0.40; 95 % CI 0.27, 0.60]. Data from the indirect comparison suggested that pazopanib had a greater survival than interferon alpha (IFN-α) [HR 0.512; 95 % CI 0.326, 0.802] but provided no evidence of any difference compared with sunitinib (HR 0.949; 95 % CI 0.575, 1.568). With regard to overall survival, 64 % (n = 99) of patients in the pazopanib arm and 63 % (n = 49) of patients in the placebo arm had died and a total of 51 % (n = 40) of placebo patients had crossed over to receive pazopanib. Although data were provided on an intention-to-treat basis, crossover between therapies

  16. Concomitant Chemoradiotherapy With Mitomycin C and Cisplatin in Advanced Unresectable Carcinoma of the Head and Neck: Phase I-II Clinical Study

    SciTech Connect

    Strojan, Primoz Karner, Katarina; Smid, Lojze; Soba, Erika; Fajdiga, Igor; Jancar, Boris; Anicin, Aleksandar; Budihna, Marjan; Zakotnik, Branko

    2008-10-01

    Purpose: To evaluate the toxicity and efficacy of concomitant chemoradiotherapy with mitomycin C and cisplatin in the treatment of advanced unresectable squamous cell carcinoma of the head and neck. Patients and Methods: Treatment consisted of conventional radiotherapy (70 Gy in 35 fractions), mitomycin C 15 mg/m{sup 2} IV, applied after the delivery of 10 Gy, and cisplatin at an initial dose of 10 mg/m{sup 2}/d IV, applied during the last 10 fractions of irradiation ('chemoboost'). The cisplatin dose was escalated with respect to the toxic side effects by 2 mg/m{sup 2}/d up to the maximum tolerated dose (MTD) or at the most 14 mg/m{sup 2}/d (Phase I study), which was tested in the subsequent Phase II study. Results: All 36 patients had Stage T4 and/or N3 disease, and the majority had oropharyngeal (50%) or hypopharyngeal (39%) primary tumors. Six patients were treated at each of the three cisplatin dose levels tested (Phase I study). Dose-limiting toxicity was not reached even at 14 mg/m{sup 2}/d of cisplatin, which was determined as the MTD and tested in an additional 18 patients (Phase II study). After a median follow-up time of 48 months, 4-year locoregional control, failure-free, and overall survival rates were 30%, 14%, and 20%, respectively. In 24 patients treated at the cisplatin dose level of 14 mg/m{sup 2}/d, the corresponding rates were 40%, 20%, and 22%, respectively. Conclusion: Concomitant chemoradiotherapy with mitomycin C and cisplatin 'chemoboost' at 14 mg/m{sup 2}/d is feasible, with encouraging survival results if the extremely poor disease profile of the treated patients is considered.

  17. Induction chemotherapy and cetuximab for locally advanced squamous cell carcinoma of the head and neck: results from a phase II prospective trial.

    PubMed

    Kies, Merrill S; Holsinger, Floyd Christopher; Lee, J Jack; William, William N; Glisson, Bonnie S; Lin, Heather Y; Lewin, Jan S; Ginsberg, Lawrence E; Gillaspy, Katharine A; Massarelli, Erminia; Byers, Lauren; Lippman, Scott M; Hong, Waun K; El-Naggar, Adel K; Garden, Adam S; Papadimitrakopoulou, Vassiliki

    2010-01-01

    PURPOSE To determine the potential efficacy of combining cetuximab with chemotherapy in patients with advanced nodal disease, we conducted a phase II trial with induction chemotherapy (ICT) consisting of six weekly cycles of paclitaxel 135 mg/m(2) and carboplatin (area under the curve = 2) with cetuximab 400 mg/m(2) in week 1 and then 250 mg/m(2) (PCC). PATIENTS AND METHODS Forty-seven previously untreated patients (41 with oropharynx primaries; 33 men, 14 women; median age, 53 years; performance status of 0 or 1) with squamous cell carcinoma of the head and neck (SCCHN; T1-4, N2b/c/3) were treated and evaluated for clinical and radiographic response. After ICT, patients underwent risk-based local therapy, which consisted of either radiation, concomitant chemoradiotherapy, or surgery, based on tumor stage and site at diagnosis. Results After induction PCC, nine patients (19%) achieved a complete response, and 36 patients (77%) achieved a partial response. The most common grade 3 or 4 toxicity was skin rash (45%), followed by neutropenia (21%) without fever. At a median follow-up time of 33 months, locoregional or systemic disease progression was observed in six patients. The 3-year progression-free survival (PFS) and overall survival (OS) rates were 87% (95% CI, 78% to 97%) and 91% (95% CI, 84% to 99%), respectively. Human papillomavirus (HPV) 16, found in 12 (46%) of 26 biopsies, was associated with improved PFS (P = .012) and OS (P = .046). CONCLUSION ICT with weekly PCC followed by risk-based local therapy seems to be feasible, effective, and well tolerated. PFS is promising, and this sequential treatment strategy should be further investigated. Patients with HPV-positive tumors have an excellent prognosis.

  18. Radiochemotherapy for locally advanced squamous cell carcinoma of the head and neck: Higher-dose cisplatin every 3 weeks versus cisplatin/5-fluorouracil every 4 weeks.

    PubMed

    Rades, Dirk; Strojan, Primoz; Seidl, Daniel; Janssen, Stefan; Bajrovic, Amira; Kazic, Nadja; Hakim, Samer G; Wollenberg, Barbara; Schild, Steven E

    2016-09-01

    Many patients with locally advanced squamous cell carcinoma of the head and neck (LASCCHN) receive cisplatin-based radiochemotherapy. The optimal regimen is still unclear when considering both efficacy and feasibility. This study compared two regimens for locoregional control (LRC), overall survival (OS), and adverse events. Data of 329 patients with LASCCHN receiving definitive or postoperative radiochemotherapy were retrospectively analyzed. A total of 131 patients received 100 mg/m(2) cisplatin on days 1, 22, and 43 (group A), and 198 patients received 20 mg/m(2) cisplatin plus 600/1000 mg/m(2) 5-FU on days 1-5 and days 29-33 (group B). Radiochemotherapy regimens plus nine factors were compared for LRC and OS, and radiochemotherapy regimens additionally for adverse events. On univariate analysis, chemotherapy type was not associated with LRC (p = 0.36). On multivariate analysis, performance score (p = 0.039), N-category (p = 0.007), histologic grade (p = 0.007), upfront surgery (p = 0.030), and pre-radiochemotherapy hemoglobin levels (p < 0.001) were associated with LRC. On univariate analysis, chemotherapy type had no impact on OS (p = 0.64). On multivariate analysis, performance score (p < 0.001), T-category (p = 0.025), N-category (p < 0.001), histologic grade, and hemoglobin levels (p < 0.001) were associated with OS. Renal failure occurred significantly more often in group A (p = 0.008). Otherwise, adverse events were not significantly different. Thus, both radiochemotherapy regimens appeared similarly effective for LASCCHN. Patients receiving 100 mg/m(2) of cisplatin require close monitoring of their renal function. PMID:27499514

  19. A Phase II Clinical Trial of Concurrent Helical Tomotherapy plus Cetuximab Followed by Adjuvant Chemotherapy with Cisplatin and Docetaxel for Locally Advanced Nasopharyngeal Carcinoma

    PubMed Central

    Zhang, Xinxin; Du, Lei; Zhao, Feifang; Wang, Qiuju; Yang, Shiming; Ma, Lin

    2016-01-01

    Purpose: The present clinical trial was designed to evaluate the efficacy and safety of concurrent helical tomotherapy (HT) with cetuximab followed by adjuvant chemotherapy with docetaxel and cisplatin (TP) in the treatment of patients with locoregionally advanced nasopharyngeal carcinoma. Materials and Methods: This phase II clinical trial included 43 patients with Stage III/IV LANC (33 Stage III and 10 Stage IV). The treatment consisted of concurrent HT with cetuximab (400 mg/m2 loading dose and weekly 250mg/m2), followed by four cycles of chemotherapy [docetaxel (70 mg/m2 on Day 1) and cisplatin (40 mg/m2 on Days 1 and 2 every 3 weeks). Side effects were evaluated with CTCAE criteria (Common Terminology Criteria for Adverse Events 3.0). Results: The median follow-up duration was 48.0 months [95% confidence interval (CI) 41.7-58.0 months], the 2-year locoregional failure-free rate (LFFR), progression-free survival (PFS), distant failure-free rate (DFFR) and overall survival (OS) were 95.2%, 79.1%, 88.1% and 93.0% respectively; the 3-year LFFR, DFFR, PFS and OS were 92.7%, 85.6%, 72.0% and 85.7% respectively. The most common grade 3 toxicities were oropharyngeal mucositis (81.4%) and RT-related dermatitis (7.0%). No patients had more than grade 3 radiation related toxicities and no patients required nasogastric feeding. One patient experienced grade 3 osteonecrosis at 18 months after treatment. Conclusions: Concurrent HT with cetuximab followed by adjuvant chemotherapy with TP is an effective strategy for the treatment of LANC with encouraging survival rates and minimal side effects. PMID:27019628

  20. Impact of Metronomic UFT/Cyclophosphamide Chemotherapy and Antiangiogenic Drug Assessed in a New Preclinical Model of Locally Advanced Orthotopic Hepatocellular Carcinoma1

    PubMed Central

    Tang, Terence C; Man, Shan; Lee, Christina R; Xu, Ping; Kerbel, Robert S

    2010-01-01

    Hepatocellular carcinoma (HCC) is an intrinsically chemotherapy refractory malignancy. Development of effective therapeutic regimens would be facilitated by improved preclinical HCC models. Currently, most models consist of subcutaneous human tumor transplants in immunodeficient mice; however, these do not reproduce the extensive liver disease associated with HCC or metastasize. To address this deficiency, we developed an orthotopic model. Human HCC cells were transfected with the gene encoding secretable β-subunit human choriogonadotropin (β-hCG), which was used as a surrogate marker of tumor burden. The HCC cells were implanted into the left liver lobe of severe combined immunodeficient (SCID) mice, after which the efficacy of different therapies was evaluated on established, but liver-confined human Hep3B cell line HCC. Treatments included sorafenib or metronomic chemotherapy using cyclophosphamide (CTX), UFT, an oral 5-fluorouracil prodrug, or doxorubicin either alone or in various combinations, with or without an antiangiogenic agent, DC101, an anti-vascular endothelial growth factor receptor-2 antibody. Sorafenib inhibited tumor growth in a dose-dependent manner but caused severe weight loss in SCID mice, thus necessitating use of DC101 in subsequent experiments. Although less toxicity was observed using either single or doublet metronomic chemotherapy without any added antiangiogenic agent, none, provided survival benefit. In contrast, significantly improved overall survival was observed using various combinations of metronomic chemotherapy regimens such as UFT + CTX with DC101. In conclusion, using this model of liver-confined but advanced HCC suggests that the efficacy of a targeted antiangiogenic drug or metronomic chemotherapy can be mutually enhanced by concurrent combination treatment. PMID:20234820

  1. Induction of thymidine phosphorylase as a pharmacodynamic end-point in patients with advanced carcinoma treated with 5-fluorouracil, folinic acid and interferon alpha

    PubMed Central

    Braybrooke, J P; Propper, D J; O’Byrne, K J; Koukourakis, M I; Patterson, A V; Houlbrook, S; Love, S D; Varcoe, S; Taylor, M; Ganesan, T S; Talbot, D C; Harris, A L

    2000-01-01

    Thymidine phosphorylase (TP) is an essential enzyme for the biochemical activation of 5-fluorouracil (5-FU). Interferon upregulates TP in vivo, although the dose and schedule of interferon for optimal biomodulation of 5-FU is not known. In this study, TP activity was measured in peripheral blood lymphocytes (PBLs) from patients with advanced carcinoma receiving treatment with 5-FU and folinic acid. Cohorts of patients were treated with interferon alpha (IFNα), immediately prior to 5-FU/folinic acid, at doses of 3 MIU m–2, 9 MIU m–2and 18 MIUm–2. IFNα was administered on day 0 cycle two, day –1 and day 0 cycle three and day –2, day –1 and day 0 cycle four. A fourth cohort was treated with IFNα 9 MIU m–2three times per week from cycle 2 onwards. Twenty-one patients were entered into the study with 19 evaluable for response. Six patients (32%) had stable disease and 13 (68%) progressive disease. There were no grade-IV toxicities. TP activity was detected in PBLs from all patients with wide interpatient variability in constitutive TP activity prior to chemotherapy, and in response to IFNα. 5-FU/folinic acid alone did not induce TP activity but a single dose of IFNα led to upregulation of TP within 2 h of administration with a further increase by 24 h (signed rank test, P = 0.006). TP activity remained elevated for at least 13 days (signed rank test, P = 0.02). There were no significant differences in TP activity between schedules or with additional doses of IFNα. A single dose of IFNα as low as 3 MIU m–2can cause sustained elevation of PBL TP activity in vivo indicating that biochemical markers are important pharmacodynamic endpoints for developing optimal schedules of IFNα for biomodulation of 5-FU. © 2000 Cancer Research Campaign PMID:10901374

  2. Influence of Tumor Thrombus Location on the Outcome of External-beam Radiation Therapy in Advanced Hepatocellular Carcinoma With Macrovascular Invasion

    SciTech Connect

    Hou Jiazhou; Zeng Zhaochong; Zhang Jianying; Fan Jia; Zhou Jian; Zeng Mengsu

    2012-10-01

    Purpose: The present study evaluates the influence of portal vein (PV) vs. inferior vena cava (IVC) tumor thrombosis sites on the effectiveness of external-beam radiation therapy (EBRT) in advanced hepatocellular carcinoma (HCC) with macrovascular invasion. Methods and Materials: We retrospectively reviewed 181 HCC patients with PV and/or IVC tumor thrombi who were referred for EBRT at our institution between 2000 and 2009. EBRT was designed to focus on the tumor thrombi with or without primary intrahepatic tumors to deliver a median total conventional dose of 50 Gy (range, 30-60 Gy). Predictors of survival were identified using univariate and multivariate analyses. Results: The median survival was 10.2, 7.4, 17.4, and 8.5 months for patients with PV branch, PV trunk, IVC, and PV plus IVC tumor thrombosis, respectively. Unfavorable pretreatment predictors were associated by multivariate analysis with lower albumin and higher {alpha}-fetoprotein levels, poorer Child-Pugh liver function classification, multiple intrahepatic foci, lymph node metastases, thrombus location, less chance to receive post-EBRT transarterial chemoembolization (TACE) and the two-dimensional EBRT technique. In comparison to patients with PV tumor thrombosis, patients with IVC thrombi had a higher occurrence of solitary intrahepatic lesions (p = 0.027), well-controlled intrahepatic tumors (p < 0.001), and a better response to EBRT (p < 0.001), and they were more likely to receive post-EBRT TACE (p = 0.033). Conclusions: In HCC, patients with IVC thrombus treated with EBRT had a better response rate and longer survival than those with PV thrombus.

  3. Feasibility of radiotherapy or chemoradiotherapy after taxane-based induction chemotherapy for nonoperated locally advanced head and neck squamous cell carcinomas.

    PubMed

    Levy, Antonin; Blanchard, Pierre; Bellefqih, Sara; Brahimi, Nacéra; Guigay, Joël; Janot, François; Temam, Stéphane; Daly-Schveitzer, Nicolas; Bourhis, Jean; Tao, Yungan

    2014-11-01

    To assess the use of radiotherapy (RT) or concurrent chemoradiotherapy (CRT) following taxane-based induction chemotherapy (T-ICT) in locally advanced head and neck squamous cell carcinoma (LAHNSCC) and to evaluate the tolerability of CRT after T-ICT. From 01/2006 to 08/2012, 173 LAHNSCC patients treated as a curative intent by T-ICT, followed by definitive RT/CRT were included in this analysis. There was an 86% objective response (OR) after ICT among 154 evaluable patients. Forty-four patients received less than three cycles (25%) and 20 received only one cycle of T-ICT. The 3-year actuarial overall survival (OS) was 49% and there was no OS difference according to the type of ICT (regimen or number of cycle) or the addition of concurrent CT (cisplatin, carboplatin, or cetuximab) to RT. In multivariate analysis (MVA), clinically involved lymph node (cN+), age more than 60 years, the absence of OR after ICT, and performance status of at least 1 predicted for a decreased OS, with hazard ratios (HR) of 2.8, 2.2, 2.1, and 2, respectively. The 3-year actuarial locoregional control (LRC) and distant control (DC) rates were 52 and 73%, respectively. In MVA, the absence of OR after ICT (HR: 3.2), cN+ (HR: 3), and age more than 60 years (HR: 1.7) were prognostic for a lower LRC whereas cN+ (HR: 4.2) and carboplatin-based T-ICT (HR: 2.9) were prognostic for a lower DC. The number of cycles (≤ 2) received during ICT was borderline significant for DC in the MVA (P=0.08). Among patients receiving less than or equal to three cycles of ICT, higher outcomes were observed in patients who received cisplatin-based T-ICT (vs. carboplatin-based T-ICT) or subsequent CRT (vs. RT). T-ICT in our experience, followed by RT or CRT, raises several questions on the role and type of induction, and the efficacy of CRT over RT. The role of RT or CRT following induction, although feasible in these advanced patients, awaits answers from randomized trials.

  4. c-Met Expression Is a Marker of Poor Prognosis in Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma Treated With Chemoradiation

    SciTech Connect

    Baschnagel, Andrew M.; Williams, Lindsay; Hanna, Alaa; Chen, Peter Y.; Krauss, Daniel J.; Pruetz, Barbara L.; Akervall, Jan; Wilson, George D.

    2014-03-01

    Purpose: To examine the prognostic significance of c-Met expression in relation to p16 and epidermal growth factor receptor (EGFR) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated with definitive concurrent chemoradiation. Methods and Materials: Archival tissue from 107 HNSCC patients treated with chemoradiation was retrieved, and a tissue microarray was assembled. Immunohistochemical staining of c-Met, p16, and EGFR was performed. c-Met expression was correlated with p16, EGFR, clinical characteristics, and clinical endpoints including locoregional control (LRC), distant metastasis (DM), disease-free survival (DFS), and overall survival (OS). Results: Fifty-one percent of patients were positive for p16, and 53% were positive for EGFR. Both p16-negative (P≤.001) and EGFR-positive (P=.019) status predicted for worse DFS. Ninety-three percent of patients stained positive for c-Met. Patients were divided into low (0, 1, or 2+ intensity) or high (3+ intensity) c-Met expression. On univariate analysis, high c-Met expression predicted for worse LRC (hazard ratio [HR] 2.27; 95% CI, 1.08-4.77; P=.031), DM (HR 4.41; 95% CI, 1.56-12.45; P=.005), DFS (HR 3.00; 95% CI, 1.68-5.38; P<.001), and OS (HR 4.35; 95% CI, 2.13-8.88; P<.001). On multivariate analysis, after adjustment for site, T stage, smoking history, and EGFR status, only high c-Met expression (P=.011) and negative p16 status (P=.003) predicted for worse DFS. High c-Met expression was predictive of worse DFS in both EGFR-positive (P=.032) and -negative (P=.008) patients. In the p16-negative patients, those with high c-Met expression had worse DFS (P=.036) than did those with low c-Met expression. c-Met expression was not associated with any outcome in the p16-positive patients. Conclusions: c-Met is expressed in the majority of locally advanced HNSCC cases, and high c-Met expression predicts for worse clinical outcomes. High c-Met expression predicted for worse DFS in p16

  5. Oxygenation in Cervical Cancer and Normal Uterine Cervix assessed using BOLD MRI at 3 T1

    PubMed Central

    Hallac, Rami R.; Ding, Yao; Yuan, Qing; McColl, Roderick W.; Lea, Jayanthi; Sims, Robert D.; Weatherall, Paul T.; Mason, Ralph P.

    2012-01-01

    Hypoxia is reported to be a biomarker for poor prognosis in cervical cancer. However, a practical non-invasive method is needed for routine clinical evaluation of tumor hypoxia. This study examined the potential use of BOLD (Blood Oxygenation Level Dependent) contrast MRI as a non-invasive technique to assess tumor vascular oxygenation at 3 T. Following IRB-approved informed consent and in compliance with HIPAA, successful results were achieved in nine patients with locally advanced cervical cancer (FIGO stage IIA to IVA) and three normal volunteers. In the first four patients, dynamic T2*-weighted MRI was performed in the transaxial plane using a multi-shot EPI sequence while patients breathed room air followed by oxygen (15 dm3/min). Later, a multi-echo gradient echo examination was added to provide quantitative R2* measurements. Baseline T2*-weighted signal intensity was quite stable, but increased to various extents in tumors upon initiation of oxygen breathing. Signal in normal uterus increased significantly, while iliacus muscle did not change. R2* responded significantly in healthy uterus, cervix, and eight cervical tumors. This preliminary study demonstrates that BOLD MRI of cervical cancer at 3 T is feasible. However, more patients must be evaluated and followed clinically before any prognostic value can be determined. PMID:22619091

  6. Examination of the uterine cervix by ultrasound in normal and pathologic pregnancy.

    PubMed

    Lampé, L; Tóth, Z; Kóródi, I; Ditrói, P

    1986-01-01

    New possibilities of examination of the uterine cervix are provided by sonography in normal and pathologic pregnancy. Basic data of the ultrasonographic anatomy of the non pregnant uterine cervix is presented first: the length of the cervix as well as the diameters at the levels of external and internal os. These data are compared then with those in normal, physiologic pregnancy, and contrasted with those obtained in cases of incompetent cervix. In this group shortening of the cervical length, opening of the internal os and the funnel, or hour-glass-like herniation of the fetal membranes were characteristic findings. The method seems to be suitable for the assessment of the effectivity of cerclage operations for cervical incompetence. PMID:3295742

  7. UV-fluorescence spectroscopic technique in the diagnosis of breast, ovarian, uterus, and cervix cancer

    NASA Astrophysics Data System (ADS)

    Das, Bidyut B.; Glassman, Wenling S.; Alfano, Robert R.; Cleary, Joseph; Prudente, R.; Celmer, Edward J.; Lubicz, Stephanie

    1991-06-01

    Malignant breast tumors can be separated from benign and normal tissues using uv-fluorescence spectroscopic technique. Using the same method one can also distinguish cancerous tissues from noncancerous ones in case of cervix, uterus and ovary.

  8. [Practical experience of endotelon application in patients with cervix uteri cancer after extended panhysterectomy].

    PubMed

    Dolyk, S S

    2004-06-01

    Application of endotelon in early period after extended panhysterectomy in patients with cervix uteri cancer of I-II stages promotes reduction of the occurrence frequency of retroperitoneal lymphatic cyst and lymphostasis in parametrium and lower extremities.

  9. [Vaginal ultrasound study of the normal and incompetent cervix: attempting a mathematical assessment].

    PubMed

    Eppel, W; Frigo, P; Schurz, B; Reinold, E

    1990-08-01

    A group of 217 pregnant patients was examined by vaginosonography. The group could be divided into 62 patients with incompetent cervix and 155 patients with normal findings. We measured the width of the internal os, the length and the thickness of cervix of all patients in intervals of 14 days. We registered a dynamic process pattern of cervical, morphological changes in the group with preterm delivery. We tried to reduce these cervical changes to an arithmetic formula. PMID:2259911

  10. [The cervix in primiparous women. A series of 320 perineal echographies].

    PubMed

    Lumbroso, P; Livache, C; Lewin, D

    1983-01-01

    Perineal ultrasound was carried out on a series of 320 primiparous women at their first antenatal visit. The results obtained show that an internal of that was larger than 20 mm was abnormal. A sign of a short cervix (less than 40 mm long on ultrasound) was of not much value but had to be taken notice of. In six cases it was found that clinically the cervix was absolutely normal and on ultrasound was incompetent. PMID:6655209

  11. Comparison of Measurements of the Uterus and Cervix Obtained by Magnetic Resonance and Transabdominal Ultrasound Imaging to Identify the Brachytherapy Target in Patients With Cervix Cancer

    SciTech Connect

    Dyk, Sylvia van; Kondalsamy-Chennakesavan, Srinivas; Schneider, Michal; Bernshaw, David; Narayan, Kailash

    2014-03-15

    Purpose: To compare measurements of the uterus and cervix obtained with magnetic resonance imaging (MRI) and transabdominal ultrasound to determine whether ultrasound can identify the brachytherapy target and be used to guide conformal brachytherapy planning and treatment for cervix cancer. Methods and Materials: Consecutive patients undergoing curative treatment with radiation therapy between January 2007 and March 2012 were included in the study. Intrauterine applicators were inserted into the uterine canal while patients were anesthetized. Images were obtained by MRI and transabdominal ultrasound in the longitudinal axis of the uterus with the applicator in treatment position. Measurements were taken at the anterior and posterior surface of the uterus at 2.0-cm intervals along the applicator, from the external os to the tip of the applicator. Data were analyzed using Bland Altman plots examining bias and 95% limits of agreement. Results: A total of 192 patients contributed 1668 measurements of the cervix and uterus. Mean (±SD) differences of measurements between imaging modalities at the anterior and posterior uterine surface ranged from 1.5 (±3.353) mm to 3.7 (±3.856) mm, and −1.46 (±3.308) mm to 0.47 (±3.502) mm, respectively. The mean differences were less than 3 mm in the cervix. The mean differences were less than 1.5 mm at all measurement points on the posterior surface. Conclusion: Differences in the measurements of the cervix and uterus obtained by MRI and ultrasound were within clinically acceptable limits. Transabdominal ultrasound can be substituted for MRI in defining the target volume for conformal brachytherapy treatment of cervix cancer.

  12. Collagen and Glycosaminoglycan Profiles in the Canine Cervix during Different Stages of the Estrous Cycle and in Open- and Closed-Cervix Pyometra

    PubMed Central

    LINHARATTANARUKSA, Pichanun; SRISUWATANASAGUL, Sayamon; PONGLOWHAPAN, Suppawiwat; KHALID, Muhammad; CHATDARONG, Kaywalee

    2013-01-01

    ABSTRACT The extracellular matrix of the cervix that comprises collagen, elastin, proteoglycans and glycosaminoglycans (GAGs) is thought to have an essential role in cervical relaxation. This study investigated the proportion of collagen and smooth muscle as well as the GAGs in cervices obtained from healthy bitches at different stages of the estrous cycle and bitches with open- and closed-cervix pyometra. Cervices were collected after ovariohysterectomy. The proportion of collagen to smooth muscle was determined using Masson’s trichrome staining. Alcian blue staining was used to evaluate the relative distribution of cervical GAGs. The proportion of cervical collagen relative to smooth muscle was higher at estrus compared to anestrus (P≤0.05). It was also higher (P≤0.05) in bitches with open- compared to those with closed-cervix pyometra. Overall, hyaluronan (HA) was the predominant GAG in the canine cervix. In the luminal epithelium, the staining intensity for HA was stronger in estrus than in anestrus (P≤0.05), but not in diestrus (P>0.05). On the contrary, the intensity for the combined keratan sulfate (KS) and heparan sulfate (HS) was stronger in anestrus than in estrus and diestrus (P≤0.05). In bitches with pyometra, the staining intensity of the stroma for KS and HS was weaker in open- compared to closed-cervix pyometra (P≤0.05). Collectively, the different profiles of collagen and GAG suggest that the metabolism of both collagen and GAGs in the canine cervix is associated with hormonal statuses during the estrous cycle and cervical patency of bitches with pathological uterine conditions, such as pyometra. PMID:24152876

  13. Collagen and glycosaminoglycan profiles in the canine cervix during different stages of the estrous cycle and in open- and closed-cervix pyometra.

    PubMed

    Linharattanaruksa, Pichanun; Srisuwatanasagul, Sayamon; Ponglowhapan, Suppawiwat; Khalid, Muhammad; Chatdarong, Kaywalee

    2014-03-01

    The extracellular matrix of the cervix that comprises collagen, elastin, proteoglycans and glycosaminoglycans (GAGs) is thought to have an essential role in cervical relaxation. This study investigated the proportion of collagen and smooth muscle as well as the GAGs in cervices obtained from healthy bitches at different stages of the estrous cycle and bitches with open- and closed-cervix pyometra. Cervices were collected after ovariohysterectomy. The proportion of collagen to smooth muscle was determined using Masson's trichrome staining. Alcian blue staining was used to evaluate the relative distribution of cervical GAGs. The proportion of cervical collagen relative to smooth muscle was higher at estrus compared to anestrus (P≤0.05). It was also higher (P≤0.05) in bitches with open- compared to those with closed-cervix pyometra. Overall, hyaluronan (HA) was the predominant GAG in the canine cervix. In the luminal epithelium, the staining intensity for HA was stronger in estrus than in anestrus (P≤0.05), but not in diestrus (P>0.05). On the contrary, the intensity for the combined keratan sulfate (KS) and heparan sulfate (HS) was stronger in anestrus than in estrus and diestrus (P≤0.05). In bitches with pyometra, the staining intensity of the stroma for KS and HS was weaker in open- compared to closed-cervix pyometra (P≤0.05). Collectively, the different profiles of collagen and GAG suggest that the metabolism of both collagen and GAGs in the canine cervix is associated with hormonal statuses during the estrous cycle and cervical patency of bitches with pathological uterine conditions, such as pyometra. PMID:24152876

  14. Collagen and glycosaminoglycan profiles in the canine cervix during different stages of the estrous cycle and in open- and closed-cervix pyometra.

    PubMed

    Linharattanaruksa, Pichanun; Srisuwatanasagul, Sayamon; Ponglowhapan, Suppawiwat; Khalid, Muhammad; Chatdarong, Kaywalee

    2014-03-01

    The extracellular matrix of the cervix that comprises collagen, elastin, proteoglycans and glycosaminoglycans (GAGs) is thought to have an essential role in cervical relaxation. This study investigated the proportion of collagen and smooth muscle as well as the GAGs in cervices obtained from healthy bitches at different stages of the estrous cycle and bitches with open- and closed-cervix pyometra. Cervices were collected after ovariohysterectomy. The proportion of collagen to smooth muscle was determined using Masson's trichrome staining. Alcian blue staining was used to evaluate the relative distribution of cervical GAGs. The proportion of cervical collagen relative to smooth muscle was higher at estrus compared to anestrus (P≤0.05). It was also higher (P≤0.05) in bitches with open- compared to those with closed-cervix pyometra. Overall, hyaluronan (HA) was the predominant GAG in the canine cervix. In the luminal epithelium, the staining intensity for HA was stronger in estrus than in anestrus (P≤0.05), but not in diestrus (P>0.05). On the contrary, the intensity for the combined keratan sulfate (KS) and heparan sulfate (HS) was stronger in anestrus than in estrus and diestrus (P≤0.05). In bitches with pyometra, the staining intensity of the stroma for KS and HS was weaker in open- compared to closed-cervix pyometra (P≤0.05). Collectively, the different profiles of collagen and GAG suggest that the metabolism of both collagen and GAGs in the canine cervix is associated with hormonal statuses during the estrous cycle and cervical patency of bitches with pathological uterine conditions, such as pyometra.

  15. Thyroid carcinoma, version 2.2014.

    PubMed

    Tuttle, R Michael; Haddad, Robert I; Ball, Douglas W; Byrd, David; Dickson, Paxton; Duh, Quan-Yang; Ehya, Hormoz; Haymart, Megan; Hoh, Carl; Hunt, Jason P; Iagaru, Andrei; Kandeel, Fouad; Kopp, Peter; Lamonica, Dominick M; Lydiatt, William M; McCaffrey, Judith; Moley, Jeffrey F; Parks, Lee; Raeburn, Christopher D; Ridge, John A; Ringel, Matthew D; Scheri, Randall P; Shah, Jatin P; Sherman, Steven I; Sturgeon, Cord; Waguespack, Steven G; Wang, Thomas N; Wirth, Lori J; Hoffmann, Karin G; Hughes, Miranda

    2014-12-01

    These NCCN Guidelines Insights focus on some of the major updates to the 2014 NCCN Guidelines for Thyroid Carcinoma. Kinase inhibitor therapy may be used to treat thyroid carcinoma that is symptomatic and/or progressive and not amenable to treatment with radioactive iodine. Sorafenib may be considered for select patients with metastatic differentiated thyroid carcinoma, whereas vandetanib or cabozantinib may be recommended for select patients with metastatic medullary thyroid carcinoma. Other kinase inhibitors may be considered for select patients with either type of thyroid carcinoma. A new section on "Principles of Kinase Inhibitor Therapy in Advanced Thyroid Cancer" was added to the NCCN Guidelines to assist with using these novel targeted agents.

  16. [Laparoscopic ligation of the internal iliac artery in bleeding cervix carcinoma].

    PubMed

    Skret, A; Obrzut, B; Stachurski, J

    1995-01-01

    Laparoscopic ligation of internal iliac artery was performed in two patients with bleeding from stage II cervical cancer. The hemostatic effect, shortening of convalescence and early initiation of radiotherapy was obtained. Additionally, during procedure the lymph node sampling was performed. Laparoscopy appeared to be an alternative procedure to abdominal or extraperitoneal ligation of internal iliac artery. PMID:7483884

  17. Risk factors for invasive carcinoma of the uterine cervix in Latin America.

    PubMed

    Herrero, R; Brinton, L A; Reeves, W C; Brenes, M M; Tenorio, F; de Britton, R C; Gaitán, E; Montalván, P; García, M; Rawls, W E

    1990-01-01

    A study of 759 cervical cancer patients, 1,430 controls, and 689 sex partners in four Latin American countries has made it possible to assess the influence of multiple factors upon the risk of invasive cervical cancer. The principal risk factors identified were the woman's age at first coitus, the number of her steady sex partners, her number of live births, the presence of DNA from human papillomavirus (HPV) types 16 or 18, a history of venereal disease, nonparticipation in early detection programs, and low socioeconomic status. There is good reason to believe that extensive detection programs directed mainly at high-risk groups in the Americas can reduce the high incidence of cervical cancer in this Region. PMID:2171706

  18. The effect of hyaluronic acid (Cicatridine) on healing and regeneration of the uterine cervix and vagina and vulvar dystrophy therapy.

    PubMed

    Markowska, J; Madry, R; Markowska, A

    2011-01-01

    Procedures aimed at the treatment of precancerous lesions and ectopia on the uterine cervix are frequently linked to lesions of anatomical structures. The application of hyaluronic acid (Cicatridine vaginal ovules) promotes accelerated healing of the uterine cervix and acquisition of a normal shape in the uterine cervix canal. Local application of hyaluronic acid in the vagina following radiotherapy due to cancer in the uterine cervix or endometrium favourably affects the healing of post-irradiation lesions in the vagina and improves quality of life. Over 90% of patients responded positively to the application of hyaluronic acid in the form of a cream on dystrophic lesions in the vulva. Hyaluronic acid aids the healing process of post-procedural wounds in the uterine cervix, following radiotherapy applied due to cancer of the uterine cervix, endometrium and in vulvar dystrophy.

  19. SUCCINCT: An Open-label, Single-arm, Non-randomised, Phase 2 Trial of Gemcitabine and Cisplatin Chemotherapy in Combination with Sunitinib as First-line Treatment for Patients with Advanced Urothelial Carcinoma

    PubMed Central

    Geldart, Thomas; Chester, John; Casbard, Angela; Crabb, Simon; Elliott, Tony; Protheroe, Andrew; Huddart, Robert A.; Mead, Graham; Barber, Jim; Jones, Robert J.; Smith, Joanna; Cowles, Robert; Evans, Jessica; Griffiths, Gareth

    2015-01-01

    Gemcitabine and cisplatin chemotherapy (GC regimen) represents a standard treatment