Does chronomodulated radiotherapy improve pathological response in locally advanced rectal cancer?

PubMed

Squire, Tim; Buchanan, Grant; Rangiah, David; Davis, Ian; Yip, Desmond; Chua, Yu Jo; Rich, Tyvin; Elsaleh, Hany

2017-01-01

The predominant mode of radiation-induced cell death for solid tumours is mitotic catastrophe, which is in part dependent on sublethal damage repair being complete at around 6 h. Circadian variation appears to play a role in normal cellular division, and this could influence tumour response of radiation treatment depending on the time of treatment delivery. We tested the hypothesis that radiation treatment later in the day may improve tumour response and nodal downstaging in rectal cancer patients treated neoadjuvantly with radiation therapy. Recruitment was by retrospective review of 267 rectal cancer patients treated neoadjuvantly in the Department of Radiation Oncology at the Canberra Hospital between January 2010 and November 2015. One hundred and fifty-five patients met the inclusion criteria for which demographic, pathological and imaging data were collected, as well as the time of day patients received treatment with each fraction of radiotherapy. Data analysis was performed using the Statistical Package R with nonparametric methods of significance for all tests set at p < 0.05. Of the 45 female and 110 male patients, the median age was 64. Seventy-three percent had cT3 disease and there was a mean tumour distance from the anal verge of 7 cm. Time to surgical resection following radiotherapy ranged from 4 to 162 days with a median of 50 days, with a complete pathological response seen in 21% of patients. Patients exhibiting a favourable pathological response had smaller median pre- and postradiotherapy tumour size and had a greater change in tumour size following treatment (p < 0.01). Patients who received the majority of their radiotherapy fractions after 12:00 pm were more likely to show a complete or moderate pathological response (p = 0.035) and improved nodal downstaging. There were also more favourable responses amongst patients with longer time to surgical resection postradiotherapy (p < 0.004), although no relationship was seen between response and tumour distance from the anal verge. Females were less likely to exhibit several of the above responses. Neoadjuvant radiotherapy for locally advanced rectal cancer performed later in the day coupled with a longer time period to surgical resection may improve pathological tumour response rates and nodal downstaging. A prospective study in chronomodulated radiotherapy in this disease is warranted.

Pre-treatment neutrophil to lymphocyte ratio as a predictive marker for pathological response to preoperative chemoradiotherapy in pancreatic cancer

PubMed Central

HASEGAWA, SHINICHIRO; EGUCHI, HIDETOSHI; TOMOKUNI, AKIRA; TOMIMARU, YOSHITO; ASAOKA, TADAFUMI; WADA, HIROSHI; HAMA, NAOKI; KAWAMOTO, KOICHI; KOBAYASHI, SHOGO; MARUBASHI, SHIGERU; KONNNO, MASAMITSU; ISHII, HIDESHI; MORI, MASAKI; DOKI, YUICHIRO; NAGANO, HIROAKI

2016-01-01

An elevated neutrophil to lymphocyte ratio (NLR) has been reported to be associated with the pathological response to neoadjuvant therapies in numerous types of cancer. The aim of the current study was to clarify the association between pre-treatment NLR and the pathological response to preoperative chemoradiotherapy in pancreatic cancer patients. This retrospective analysis included data from 56 consecutive patients whose tumors were completely surgically resected. All patients received preoperative therapy, consisting of gemcitabine-based chemotherapy (alone or in combination with S-1) combined with 40 or 50.4 Gy irradiation, prior to surgery. Predictive factors, including NLR, platelet to lymphocyte ratio (PLR), modified Glasgow prognostic score and prognostic nutrition index, were measured prior to treatment. A comparison was made between those who responded well pathologically (good response group, Evans classification IIb/III) and those with a poor response (Evans I/IIa). NLR was determined to be significantly higher in the poor response group. Multivariate analysis identified an elevated NLR as an independent risk factor for the poor pathological response [odds ratio (OR), 5.35; P=0.0257]. The pre-treatment NLR (≥2.2/<2.2) was found to be a statistically significant predictive indicator of pathological response (P=0.00699). The results demonstrate that pre-treatment NLR may be a useful predictive marker for the pathological response to preoperative therapy in pancreatic cancer patients. PMID:26893780

Social Information Processing and Cluster B Personality Pathology among Clinic-Referred Adolescents.

PubMed

Hessels, Christel; van Aken, Marcel A G; Orobio de Castro, Bram; Laceulle, Odilia M; van Voorst, Guus

2016-01-01

This study investigated relations between personality pathology and mentalizing capacities reflected in social information processing (SIP) of adolescents. 96 adolescent outpatients completed a structured interview regarding SIP. Their clinicians completed a checklist based on DSM-IV, assessing severity of personality pathology. Significant relations were found between the severity of personality pathology and SIP: the more severe the personality pathology, the higher the intensity of reported emotions, the more likely adolescents were to choose inadequate coping strategies and aggressive reactions in social situations, and the more positively they evaluated aggressive reactions. Severity of traits of antisocial (ASPD) and borderline personality disorder (BPD) had unique associations with distinctive SIP variables: ASPD being more related to inadequate coping strategies, less reflection on other's motives and aggressive responses, and BPD being more related to avoidant or prosocial responses and in particular to memories of frustrating events. This study provides evidence for difficulties in SIP among adolescents with more severe personality pathology, suggesting that the steps in the SIP model can be used to operationalize mentalizing problems. The results seem to paint a picture of ASPD and BPD having a shared background, but their own specific problems concerning SIP. © 2016 S. Karger AG, Basel.

Standardizing of Pathology in Patients Receiving Neoadjuvant Chemotherapy.

PubMed

Bossuyt, Veerle; Symmans, W Fraser

2016-10-01

The use of neoadjuvant systemic therapy for the treatment of breast cancer patients is increasing. Pathologic response in the form of pathologic complete response (pCR) and grading systems of partial response, such as the residual cancer burden (RCB) system, gives valuable prognostic information for patients and is used as a primary endpoint in clinical trials. The breast cancer and pathology communities are responding with efforts to standardize pathology in patients receiving neoadjuvant chemotherapy. In this review, we summarize the challenges that postneoadjuvant systemic therapy surgical specimens pose and how pathologists and the multidisciplinary team can work together to optimize handling of these specimens. Multidisciplinary communication is essential. A single, standardized approach to macroscopic and microscopic pathologic examination makes it possible to provide reliable response information. This approach employs a map of tissue sections to correlate clinical, gross, microscopic, and imaging findings in order to report the presence of pCR (ypT0 ypN0 and ypT0/is ypN0) versus residual disease, the ypT and ypN stage using the current AJCC/UICC staging system, and the RCB.

From telepathology to virtual pathology institution: the new world of digital pathology.

PubMed

Kayser, K; Kayser, G; Radziszowski, D; Oehmann, A

Telepathology has left its childhood. Its technical development is mature, and its use for primary (frozen section) and secondary (expert consultation) diagnosis has been expanded to a great amount. This is in contrast to a virtual pathology laboratory, which is still under technical constraints. Similar to telepathology, which can also be used for e-learning and e-training in pathology, as exemplarily is demonstrated on Digital Lung Pathology (Klaus.Kayser@charite.de) at least two kinds of virtual pathology laboratories will be implemented in the near future: a) those with distributed pathologists and distributed (> or = 1) laboratories associated to individual biopsy stations/surgical theatres, and b) distributed pathologists (usually situated in one institution) and a centralized laboratory, which digitizes complete histological slides. Both scenarios are under intensive technical investigations. The features of virtual pathology comprise a virtual pathology institution (mode a) that accepts a complete case with the patient's history, clinical findings, and (pre-selected) images for first diagnosis. The diagnostic responsibility is that of a conventional institution. The Internet serves as platform for information transfer, and an open server such as the iPATH (http://telepath.patho.unibas.ch) for coordination and performance of the diagnostic procedure. The size and number of transferred images have to be limited, and usual different magnifications have to be used. The sender needs to possess experiences in image sampling techniques, which present with the most significant information. A group of pathologists is "on duty", or selects one member for a predefined duty period. The diagnostic statement of the pathologist(s) on duty is retransmitted to the sender with full responsibility. The first experiences of a virtual pathology institution group working with the iPATH server working with a small hospital of the Salomon islands are promising. A centralized virtual pathology institution (mode b) depends upon the digitalization of a complete slide, and the transfer of large sized images to different pathologists working in one institution. The technical performance of complete slide digitalization is still under development. Virtual pathology can be combined with e-learning and e-training, that will serve for a powerful daily-work-integrated pathology system. At present, e-learning systems are "stand-alone" solutions distributed on CD or via Internet. A characteristic example is the Digital Lung Pathology CD, which includes about 60 different rare and common lung diseases with some features of electronic communication. These features include access to scientific library systems (PubMed), distant measurement servers (EuroQuant), automated immunohisto-chemistry measurements, or electronic journals (Elec J Pathol Histol, www.pathology-online.org). It combines e-learning and e-training with some acoustic support. A new and complete database based upon this CD will combine e-learning and e-teaching with the actual workflow in a virtual pathology institution (mode a). The technological problems are solved and do not depend upon technical constraints such as slide scanning systems. At present, telepathology serves as promoter for a complete new landscape in diagnostic pathology, the so-called virtual pathology institution. Industrial and scientific efforts will probably allow an implementation of this technique within the next two years with exciting diagnostic and scientific perspectives.

The Evoked Potential. An Experimental Method for Biomechanical Analysis of Brain and Spinal Injury

DTIC Science & Technology

1980-01-01

Newtons produced marked changes in blood pressure, heart rate and distraction of the cervical spinal column with minimal ligamentous disruption...pathologic distraction and pathologic flexion of the thoracic ver- tebral column (8). Cerebral responses were lost within two minutes aftex complete...However, the immediate flexion and distraction responses were not altered. These findings suggest that mechanical trauma alters the spinal cord evoked

Prediction of Response to Neoadjuvant Chemotherapy and Radiation Therapy with Baseline and Restaging 18F-FDG PET Imaging Biomarkers in Patients with Esophageal Cancer.

PubMed

Beukinga, Roelof J; Hulshoff, Jan Binne; Mul, Véronique E M; Noordzij, Walter; Kats-Ugurlu, Gursah; Slart, Riemer H J A; Plukker, John T M

2018-06-01

Purpose To assess the value of baseline and restaging fluorine 18 ( 18 F) fluorodeoxyglucose (FDG) positron emission tomography (PET) radiomics in predicting pathologic complete response to neoadjuvant chemotherapy and radiation therapy (NCRT) in patients with locally advanced esophageal cancer. Materials and Methods In this retrospective study, 73 patients with histologic analysis-confirmed T1/N1-3/M0 or T2-4a/N0-3/M0 esophageal cancer were treated with NCRT followed by surgery (Chemoradiotherapy for Esophageal Cancer followed by Surgery Study regimen) between October 2014 and August 2017. Clinical variables and radiomic features from baseline and restaging 18 F-FDG PET were selected by univariable logistic regression and least absolute shrinkage and selection operator. The selected variables were used to fit a multivariable logistic regression model, which was internally validated by using bootstrap resampling with 20 000 replicates. The performance of this model was compared with reference prediction models composed of maximum standardized uptake value metrics, clinical variables, and maximum standardized uptake value at baseline NCRT radiomic features. Outcome was defined as complete versus incomplete pathologic response (tumor regression grade 1 vs 2-5 according to the Mandard classification). Results Pathologic response was complete in 16 patients (21.9%) and incomplete in 57 patients (78.1%). A prediction model combining clinical T-stage and restaging NCRT (post-NCRT) joint maximum (quantifying image orderliness) yielded an optimism-corrected area under the receiver operating characteristics curve of 0.81. Post-NCRT joint maximum was replaceable with five other redundant post-NCRT radiomic features that provided equal model performance. All reference prediction models exhibited substantially lower discriminatory accuracy. Conclusion The combination of clinical T-staging and quantitative assessment of post-NCRT 18 F-FDG PET orderliness (joint maximum) provided high discriminatory accuracy in predicting pathologic complete response in patients with esophageal cancer. © RSNA, 2018 Online supplemental material is available for this article.

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

PubMed

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

2014-01-17

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

Pathological response of locally advanced rectal cancer to preoperative chemotherapy without pelvic irradiation.

PubMed

Bensignor, T; Brouquet, A; Dariane, C; Thirot-Bidault, A; Lazure, T; Julié, C; Nordlinger, B; Penna, C; Benoist, S

2015-06-01

Pathological response to chemotherapy without pelvic irradiation is not well defined in rectal cancer. This study aimed to evaluate the objective pathological response to preoperative chemotherapy without pelvic irradiation in middle or low locally advanced rectal cancer (LARC). Between 2008 and 2013, 22 patients with middle or low LARC (T3/4 and/or N+ and circumferential resection margin < 2 mm) and synchronous metastatic disease or a contraindication to pelvic irradiation underwent rectal resection after preoperative chemotherapy. The pathological response of rectal tumour was analysed according to the Rödel tumour regression grading (TRG) system. Predictive factors of objective pathological response (TRG 2-4) were analysed. All patients underwent rectal surgery after a median of six cycles of preoperative chemotherapy. Of these, 20 (91%) had sphincter saving surgery and an R0 resection. Twelve (55%) patients had an objective pathological response (TRG 2-4), including one complete response. Poor response (TRG 0-1) to chemotherapy was noted in 10 (45%) patients. In univariate analyses, none of the factors examined was found to be predictive of an objective pathological response to chemotherapy. At a median follow-up of 37.2 months, none of the 22 patients experienced local recurrence. Of the 19 patients with Stage IV rectal cancer, 15 (79%) had liver surgery with curative intent. Preoperative chemotherapy without pelvic irradiation is associated with objective pathological response and adequate local control in selected patients with LARC. Further prospective controlled studies will address the question of whether it can be used as a valuable alternative to radiochemotherapy in LARC. Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.

Relationship between the Temporal Changes in Positron-Emission-Tomography-Imaging-Based Textural Features and Pathologic Response and Survival in Esophageal Cancer Patients.

PubMed

Yip, Stephen S F; Coroller, Thibaud P; Sanford, Nina N; Mamon, Harvey; Aerts, Hugo J W L; Berbeco, Ross I

2016-01-01

Although change in standardized uptake value (SUV) measures and PET-based textural features during treatment have shown promise in tumor response prediction, it is unclear which quantitative measure is the most predictive. We compared the relationship between PET-based features and pathologic response and overall survival with the SUV measures in esophageal cancer. Fifty-four esophageal cancer patients received PET/CT scans before and after chemoradiotherapy. Of these, 45 patients underwent surgery and were classified into complete, partial, and non-responders to the preoperative chemoradiation. SUVmax and SUVmean, two cooccurrence matrix (Entropy and Homogeneity), two run-length matrix (RLM) (high-gray-run emphasis and Short-run high-gray-run emphasis), and two size-zone matrix (high-gray-zone emphasis and short-zone high-gray emphasis) textures were computed. The relationship between the relative difference of each measure at different treatment time points and the pathologic response and overall survival was assessed using the area under the receiver-operating-characteristic curve (AUC) and Kaplan-Meier statistics, respectively. All Textures, except Homogeneity, were better related to pathologic response than SUVmax and SUVmean. Entropy was found to significantly distinguish non-responders from the complete (AUC = 0.79, p = 1.7 × 10(-4)) and partial (AUC = 0.71, p = 0.01) responders. Non-responders can also be significantly differentiated from partial and complete responders by the change in the run-length and size-zone matrix textures (AUC = 0.71-0.76, p ≤ 0.02). Homogeneity, SUVmax, and SUVmean failed to differentiate between any of the responders (AUC = 0.50-0.57, p ≥ 0.46). However, none of the measures were found to significantly distinguish between complete and partial responders with AUC <0.60 (p = 0.37). Median Entropy and RLM textures significantly discriminated patients with good and poor survival (log-rank p < 0.02), while all other textures and survival were poorly related (log-rank p > 0.25). For the patients studied, temporal changes in Entropy and all RLM were better correlated with pathological response and survival than the SUV measures. The hypothesis that these metrics can be used as clinical predictors of better patient outcomes will be tested in a larger patient dataset in the future.

Matrix metalloproteinase-9 expression correlated with tumor response in patients with locally advanced rectal cancer undergoing preoperative chemoradiotherapy

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

Unsal, Diclehan; Uner, Aytug; Akyurek, Nalan

2007-01-01

Purpose: To analyze whether the expression of matrix metalloproteinases (MMPs) and their tissue inhibitors are associated with tumor response to preoperative chemoradiotherapy in rectal cancer patients. Methods and Materials: Forty-four patients who had undergone preoperative chemoradiotherapy were evaluated retrospectively. Treatment consisted of pelvic radiotherapy and two cycles of 5-fluorouracil plus leucovorin. Surgery was performed 6-8 weeks later. MMP-2, MMP-9, and tissue inhibitors of metalloproteinase-1 and -2 expression was analyzed by immunohistochemistry of the preradiation biopsy and surgical specimens. The intensity and extent of staining were evaluated separately, and a final score was calculated by multiplying the two scores. The primarymore » endpoint was the correlation of expression with tumor response, with the secondary endpoint the effect of chemoradiotherapy on the expression. Results: Preoperative treatment resulted in downstaging in 20 patients (45%) and no clinical response in 24 (55%). The pathologic tumor response was complete in 11 patients (25%), partial in 23 (52%), and none in 10 (23%). Positive MMP-9 staining was observed in 20 tumors (45%) and was associated with the clinical nodal stage (p = 0.035) and the pathologic and clinical response (p < 0.0001). The staining status of the other markers was associated with neither stage nor response. The overall pathologic response rate was 25% in MMP-9-positive patients vs. 52% in MMP-9-negative patients (p = 0.001). None of the 11 patients with pathologic complete remission was MMP-9 positive. Conclusions: Matrix metalloproteinase-9 expression correlated with a poor tumor response to preoperative chemoradiotherapy in rectal carcinoma patients.« less

Missing metastases as a model to challenge current therapeutic algorithms in colorectal liver metastases.

PubMed

Lucidi, Valerio; Hendlisz, Alain; Van Laethem, Jean-Luc; Donckier, Vincent

2016-04-21

In oncosurgical approach to colorectal liver metastases, surgery remains considered as the only potentially curative option, while chemotherapy alone represents a strictly palliative treatment. However, missing metastases, defined as metastases disappearing after chemotherapy, represent a unique model to evaluate the curative potential of chemotherapy and to challenge current therapeutic algorithms. We reviewed recent series on missing colorectal liver metastases to evaluate incidence of this phenomenon, predictive factors and rates of cure defined by complete pathologic response in resected missing metastases and sustained clinical response when they were left unresected. According to the progresses in the efficacy of chemotherapeutic regimen, the incidence of missing liver metastases regularly increases these last years. Main predictive factors are small tumor size, low marker level, duration of chemotherapy, and use of intra-arterial chemotherapy. Initial series showed low rates of complete pathologic response in resected missing metastases and high recurrence rates when unresected. However, recent reports describe complete pathologic responses and sustained clinical responses reaching 50%, suggesting that chemotherapy could be curative in some cases. Accordingly, in case of missing colorectal liver metastases, the classical recommendation to resect initial tumor sites might have become partially obsolete. Furthermore, the curative effect of chemotherapy in selected cases could lead to a change of paradigm in patients with unresectable liver-only metastases, using intensive first-line chemotherapy to intentionally induce missing metastases, followed by adjuvant surgery on remnant chemoresistant tumors and close surveillance of initial sites that have been left unresected.

Effect of neoadjuvant chemotherapy on HER-2 expression in surgically treated gastric and oesophagogastric junction carcinoma: a multicentre Italian study.

PubMed

Chiari, Damiano; Orsenigo, Elena; Guarneri, Giovanni; Baiocchi, Gian Luca; Mazza, Elena; Albarello, Luca; Bissolati, Massimiliano; Molfino, Sarah; Staudacher, Carlo

2017-03-01

Predictors of response to neoadjuvant chemotherapy are not available for gastric and oesophago-gastric junction carcinoma. HER-2 over-expression in breast cancer correlates with poor prognosis and high incidence of recurrence. First aim of this study was to evaluate if the HER-2 expression/amplification is predictive of response to neoadjuvant chemotherapy in terms of pathologic regression. Secondary aim was to evaluate if HER-2 expression varies after neoadjuvant treatment. Thirty-five patients with locally advanced gastric or oesophago-gastric junction carcinoma underwent preoperative chemotherapy and surgical resection at San Raffaele Scientific Institute and Spedali Civili of Brescia. HER-2 expression/amplification was evaluated on every biopsy at diagnosis time and on every surgical sample after neoadjuvant chemotherapy. Pathologic response to chemotherapy was evaluated according to TNM classification (ypT status and ypN status) and Mandard's tumour regression grade classification. In our series 10 patients (28.6%) showed a reduction in HER-2 overexpression and in 6 of them (17.1%) HER-2 expression completely disappeared. Only three of the six patients with HER-2 disappearance had a complete pathological response to neoadjuvant chemotherapy. There was a strong correlation between HER-2 negativity on biopsy and absence of lymph node metastasis in surgical samples after neoadjuvant chemotherapy, irrespective of nodal status before chemotherapy. A direct correlation between HER-2 reduction after neoadjuvant chemotherapy and pathologic regression (primary tumour and lymph nodes) in surgical samples was found. HER-2 negativity may represent a predictor of pathologic response to neoadjuvant chemotherapy for gastric and oesophago-gastric junction adenocarcinoma. Neoadjuvant treatment can reduce HER-2 overexpression.

Pathological complete response following neoadjuvant radiotherapy and intraperitoneal perfusion chemotherapy for recurrent colon carcinoma: A case report and literature review

PubMed Central

BIAN, XINYU; LIU, BAORUI; YANG, YANG

2016-01-01

The present study reports the case of a 28-year-old male who was diagnosed with sigmoid colon carcinoma and exhibited local recurrence following radical surgery and 6 cycles of adjuvant chemotherapy. The primary surgery consisted of a partial sigmoidectomy and bladder repair. At 8 months post-chemotherapy, the patient was referred to Nanjing Drum Tower Hospital (Nanjing, China) due to local recurrence at the anastomotic site, which was confirmed by colonoscopy and total abdominal computed tomography. Synchronous intensity modulation radiation therapy and intraperitoneal (IP) perfusion chemotherapy with irinotecan (100 mg/m2) was administered. Following treatment, the object efficacy evaluation revealed a complete response and a second resection of the remaining sigmoid colon was performed. The post-operative results showed a pathological complete response. This case indicated that a combination of therapies, including radiotherapy, IP perfusion chemotherapy and surgery, may be beneficial and effective in patients with recurrent colon cancer. PMID:27073546

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

PubMed

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

2018-06-01

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

A central review of histopathology reports after breast cancer neoadjuvant chemotherapy in the neo-tango trial

PubMed Central

Provenzano, E; Vallier, A-L; Champ, R; Walland, K; Bowden, S; Grier, A; Fenwick, N; Abraham, J; Iddawela, M; Caldas, C; Hiller, L; Dunn, J; Earl, H M

2013-01-01

Background: Neo-tAnGo, a National Cancer Research Network (NCRN) multicentre randomised neoadjuvant chemotherapy trial in early breast cancer, enroled 831 patients in the United Kingdom. We report a central review of post-chemotherapy histopathology reports on the surgical specimens, to assess the presence and degree of response. Methods: A central independent two-reader review (EP and HME) of histopathology reports from post-treatment surgical specimens was performed. The quality and completeness of pathology reporting across all centres was assessed. The reviews included pathological response to chemotherapy (pathological complete response (pCR); minimal residual disease (MRD); and lesser degrees of response), laterality, the number of axillary metastases and axillary nodes, and the type of surgery. A consensus was reached after discussion. Results: In all, 825 surgical reports from 816 patients were available for review. Out of 4125 data items there were 347 discrepant results (8.4% of classifications), which involved 281 patients. These involved grading of breast response (169 but only 9 involving pCR vs MRD); laterality (6); presence of axillary metastasis (35); lymph node counts (108); and type of axillary surgery (29). Excluding cases with pCR, only 45% of reports included any comment regarding response in the breast and 30% in the axillary lymph nodes. Conclusion: We found considerable variability in the completeness of reporting of surgical specimens within this national neoadjuvant breast cancer trial. This highlights the need for consensus guidelines among trial groups on histopathology reporting, and the participation of histopathologists throughout the development and analysis of neoadjuvant trials. PMID:23299526

Evaluation of chemotherapy response in patients with advanced head and neck cancer using [F-18]fluorodeoxyglucose positron emission tomography.

PubMed

Lowe, V J; Dunphy, F R; Varvares, M; Kim, H; Wittry, M; Dunphy, C H; Dunleavy, T; McDonough, E; Minster, J; Fletcher, J W; Boyd, J H

1997-12-01

[F-18]Fluorodeoxyglucose (FDG)-positron emission tomography (PET) can measure the metabolic activity of tissues; FDG-PET may be able to predict response to chemotherapy by identifying changes in tumor metabolism. Measurement of response to treatment may help improve survival in the management of advanced head and neck cancer. We evaluated this particular use of FDG-PET in patients participating in a neoadjuvant organ-preservation protocol using taxol and carboplatin and compared pathologic response after chemotherapy with changes in tumor metabolism measured by FDG-PET. Serial FDG-PET studies (n = 56) were performed in patients (n = 28) with stage III/IV head and neck cancer participating in a neoadjuvant organ-preservation protocol. The FDG-PET studies were performed before and after chemotherapy. All patients had tissue biopsies before and after chemotherapy. Patients were classified as pathologic complete response (PCR) or residual disease (RD) based on tissue biopsies. Visual analysis of PET scans was performed to identify patients with complete response by PET, and these findings were compared with pathology results. Metabolic changes were also evaluated using standardized uptake ratios (SUR) of FDG. The sensitivity and specificity of PET for residual cancer after therapy was 90% (19/21) and 83% (5/6), respectively. Two patients had initially negative biopsies and positive PET studies for persistent disease. Pathology review and rebiospy led to confirmation of the PET results in these cases, giving a sensitivity of 90% for initial tissue biopsy. In this preliminary analysis, FDG-PET was accurate in classifying response to chemotherapy in most patients. Fluorodeoxyglucose-PET may identify residual viable tumor when it is otherwise undetectable.

Adaptive Randomization of Neratinib in Early Breast Cancer.

PubMed

Park, John W; Liu, Minetta C; Yee, Douglas; Yau, Christina; van 't Veer, Laura J; Symmans, W Fraser; Paoloni, Melissa; Perlmutter, Jane; Hylton, Nola M; Hogarth, Michael; DeMichele, Angela; Buxton, Meredith B; Chien, A Jo; Wallace, Anne M; Boughey, Judy C; Haddad, Tufia C; Chui, Stephen Y; Kemmer, Kathleen A; Kaplan, Henry G; Isaacs, Claudine; Nanda, Rita; Tripathy, Debasish; Albain, Kathy S; Edmiston, Kirsten K; Elias, Anthony D; Northfelt, Donald W; Pusztai, Lajos; Moulder, Stacy L; Lang, Julie E; Viscusi, Rebecca K; Euhus, David M; Haley, Barbara B; Khan, Qamar J; Wood, William C; Melisko, Michelle; Schwab, Richard; Helsten, Teresa; Lyandres, Julia; Davis, Sarah E; Hirst, Gillian L; Sanil, Ashish; Esserman, Laura J; Berry, Donald A

2016-07-07

The heterogeneity of breast cancer makes identifying effective therapies challenging. The I-SPY 2 trial, a multicenter, adaptive phase 2 trial of neoadjuvant therapy for high-risk clinical stage II or III breast cancer, evaluated multiple new agents added to standard chemotherapy to assess the effects on rates of pathological complete response (i.e., absence of residual cancer in the breast or lymph nodes at the time of surgery). We used adaptive randomization to compare standard neoadjuvant chemotherapy plus the tyrosine kinase inhibitor neratinib with control. Eligible women were categorized according to eight biomarker subtypes on the basis of human epidermal growth factor receptor 2 (HER2) status, hormone-receptor status, and risk according to a 70-gene profile. Neratinib was evaluated against control with regard to 10 biomarker signatures (prospectively defined combinations of subtypes). The primary end point was pathological complete response. Volume changes on serial magnetic resonance imaging were used to assess the likelihood of such a response in each patient. Adaptive assignment to experimental groups within each disease subtype was based on Bayesian probabilities of the superiority of the treatment over control. Enrollment in the experimental group was stopped when the 85% Bayesian predictive probability of success in a confirmatory phase 3 trial of neoadjuvant therapy reached a prespecified threshold for any biomarker signature ("graduation"). Enrollment was stopped for futility if the probability fell to below 10% for every biomarker signature. Neratinib reached the prespecified efficacy threshold with regard to the HER2-positive, hormone-receptor-negative signature. Among patients with HER2-positive, hormone-receptor-negative cancer, the mean estimated rate of pathological complete response was 56% (95% Bayesian probability interval [PI], 37 to 73%) among 115 patients in the neratinib group, as compared with 33% among 78 controls (95% PI, 11 to 54%). The final predictive probability of success in phase 3 testing was 79%. Neratinib added to standard therapy was highly likely to result in higher rates of pathological complete response than standard chemotherapy with trastuzumab among patients with HER2-positive, hormone-receptor-negative breast cancer. (Funded by QuantumLeap Healthcare Collaborative and others; I-SPY 2 TRIAL ClinicalTrials.gov number, NCT01042379.).

Systematic review of FDG-PET prediction of complete pathological response and survival in rectal cancer.

PubMed

Memon, Sameer; Lynch, A Craig; Akhurst, Timothy; Ngan, Samuel Y; Warrier, Satish K; Michael, Michael; Heriot, Alexander G

2014-10-01

Advances in the management of rectal cancer have resulted in an increased application of multimodal therapy with the aim of tailoring therapy to individual patients. Complete pathological response (pCR) is associated with improved survival and may be potentially managed without radical surgical resection. Over the last decade, there has been increasing interest in the ability of functional imaging to predict complete response to treatment. The aim of this review was to assess the role of (18)F-flurordeoxyglucose positron emission tomography (FDG-PET) in prediction of pCR and prognosis in resectable locally advanced rectal cancer. A search of the MEDLINE and Embase databases was conducted, and a systematic review of the literature investigating positron emission tomography (PET) in the prediction of pCR and survival in rectal cancer was performed. Seventeen series assessing PET prediction of pCR were included in the review. Seven series assessed postchemoradiation SUVmax, which was significantly different between response groups in all six studies that assessed this. Nine series assessed the response index (RI) for SUVmax, which was significantly different between response groups in seven series. Thirteen studies investigated PET response for prediction of survival. Metabolic complete response assessed by SUV2max or visual response and RISUVmax showed strong associations with disease-free survival (DFS) and overall survival (OS). SUV2max and RISUVmax appear to be useful FDG-PET markers for prediction of pCR and these parameters also show strong associations with DFS and OS. FDG-PET may have a role in outcome prediction in patients with advanced rectal cancer.

Complete Neoadjuvant Treatment for Rectal Cancer: The Brown University Oncology Group CONTRE Study.

PubMed

Perez, Kimberly; Safran, Howard; Sikov, William; Vrees, Matthew; Klipfel, Adam; Shah, Nishit; Schechter, Steven; Oldenburg, Nicklas; Pricolo, Victor; Rosati, Kayla; Dipetrillo, Thomas

2017-06-01

Following preoperative chemoradiation and surgery, many patients with stage II to III rectal cancer are unable to tolerate full-dose adjuvant chemotherapy. BrUOG R-224 was designed to assess the impact of COmplete Neoadjuvant Treatment for REctal cancer (CONTRE), primary chemotherapy followed by chemoradiation and surgery, on treatment delivery, toxicities, and pathologic response at surgery. Patients with clinical stage II to III (T3 to T4 and/or N1 to N2) rectal cancer received 8 cycles of modified FOLFOX6 followed by capecitabine 825 mg/m bid concurrent with 50.4 Gy intensity-modulated radiation therapy. Surgery was performed 6 to 10 weeks after chemoradiation. Thirty-nine patients were enrolled between August 2010 and June 2013. Median age was 61 years (30 to 79 y); 7 patients (18%) were clinical stage II and 32 (82%) stage III. Thirty-six patients (92%) received all 8 cycles of mFOLFOX6, of whom 35 completed subsequent chemoradiation; thus 89% of patients received CONTRE as planned. No unexpected toxicities were reported. All patients had resolution of bleeding and improvement of obstructive symptoms, with no complications requiring surgical intervention. Pathologic complete response (ypT0N0) was demonstrated in 13 patients (33%; 95% CI, 18.24%-47.76%). CONTRE seems to be a well-tolerated alternative to the current standard treatment sequence. Evaluating its impact on long-term outcomes would require a large randomized trial, but using pathologic response as an endpoint, it could serve as a platform for assessing the addition of novel agents to preoperative treatment in stage II to III rectal cancer.

Magnetic resonance imaging in breast cancer treated with neoadjuvant chemotherapy: radiologic-pathologic correlation of the response and disease-free survival depending on molecular subtype.

PubMed

Cruz Ciria, S; Jiménez Aragón, F; García Mur, C; Esteban Cuesta, H; Gros Bañeres, B

2014-01-01

To evaluate the radiologic and pathologic responses to neoadjuvant chemotherapy and their correlation in the molecular subtypes of breast cancer and to analyze their impact in disease-free survival. We included 205 patients with breast cancer treated with neoadjuvant chemotherapy. We evaluated the radiologic response by comparing MRI images acquired before and after chemotherapy. The pathologic response was classified on the Miller and Payne scale. For each subtype (HER2+, TN, luminal A, luminal B HER2-, and luminal B HER2+), we used the χ(2) test, Student's t-test, ANOVA, and Kendall's Tau-b to evaluate the radiologic response and the pathologic response, the radiologic-pathologic correlation, and the disease-free survival. The subtypes HER2+ (62.1%) and TN (45.2%) had higher rates of complete radiologic response. The pathologic response was 65.5% in the HER2+ subtype, 38.1% in the TN subtype, 2.6% in the luminal A subtype, 8.2% in the luminal B HER2- subtype, and 31% in the luminal B HER2+ subtype. The rate of radiologic-pathologic correlation was significant in all subtypes, higher in TN and HER2 (Tau-b coefficients 0.805 and 0.717, respectively). Disease-free survival was higher in HER2+ (91.9±3.3 months) and lower in TN (69.5±6.3 months), with significant differences between the cases with poor and good radiologic responses (P=.040). Survival was greater in cases with good radiologic response, except in cases with luminal A subtype. MRI can be a useful tool that provides information about the evolution of breast cancer treated with neoadjuvant chemotherapy, which varies with the immunohistochemical subtype. Copyright © 2012 SERAM. Published by Elsevier Espana. All rights reserved.

Diffusion-weighted imaging: Apparent diffusion coefficient histogram analysis for detecting pathologic complete response to chemoradiotherapy in locally advanced rectal cancer.

PubMed

Choi, Moon Hyung; Oh, Soon Nam; Rha, Sung Eun; Choi, Joon-Il; Lee, Sung Hak; Jang, Hong Seok; Kim, Jun-Gi; Grimm, Robert; Son, Yohan

2016-07-01

To investigate the usefulness of apparent diffusion coefficient (ADC) values derived from histogram analysis of the whole rectal cancer as a quantitative parameter to evaluate pathologic complete response (pCR) on preoperative magnetic resonance imaging (MRI). We enrolled a total of 86 consecutive patients who had undergone surgery for rectal cancer after neoadjuvant chemoradiotherapy (CRT) at our institution between July 2012 and November 2014. Two radiologists who were blinded to the final pathological results reviewed post-CRT MRI to evaluate tumor stage. Quantitative image analysis was performed using T2 -weighted and diffusion-weighted images independently by two radiologists using dedicated software that performed histogram analysis to assess the distribution of ADC in the whole tumor. After surgery, 16 patients were confirmed to have achieved pCR (18.6%). All parameters from pre- and post-CRT ADC histogram showed good or excellent agreement between two readers. The minimum, 10th, 25th, 50th, and 75th percentile and mean ADC from post-CRT ADC histogram were significantly higher in the pCR group than in the non-pCR group for both readers. The 25th percentile value from ADC histogram in post-CRT MRI had the best diagnostic performance for detecting pCR, with an area under the receiver operating characteristic curve of 0.796. Low percentile values derived from the ADC histogram analysis of rectal cancer on MRI after CRT showed a significant difference between pCR and non-pCR groups, demonstrating the utility of the ADC value as a quantitative and objective marker to evaluate complete pathologic response to preoperative CRT in rectal cancer. J. Magn. Reson. Imaging 2016;44:212-220. © 2015 Wiley Periodicals, Inc.

The short-term outcomes of induction SOX (S-1 + oxaliplatin) ± cetuximab chemotherapy followed by short-course chemoradiotherapy in patients with poor-risk locally advanced rectal cancer.

PubMed

Beppu, Naohito; Yoshie, Hidenori; Kimura, Fumihiko; Aihara, Tsukasa; Doi, Hiroshi; Kamikonya, Norihiko; Matsubara, Nagahide; Tomita, Naohiro; Yanagi, Hidenori; Yamanaka, Naoki

2016-10-01

To evaluate the safety and efficacy of induction SOX (S-1 + oxaliplatin) ± cetuximab chemotherapy followed by short-course chemoradiotherapy and surgery in patients with poor-risk locally advanced rectal cancer. We enrolled eligible patients with poor-risk rectal cancer defined as T3 lower rectal cancer with mesorectal fascia involvement, T4a or T4b tumors or cases with lateral lymph node swelling. The primary endpoint was a pathological complete response (pCR), and the secondary endpoints were the objective response rate (ORR) and the pathological high response rate (Grade 2 plus 3). Twenty eligible patients were enrolled. The majority (75.0 %, 15/20) of the patients completed four cycles of induction chemotherapy, and all patients completed the radiotherapy (25 Gy/10 fractions/5 days). The global rate of Grade 3-4 toxicities was 30.0 % (6/20 patients). The ORRs were 85.0 % (17/20) and 95.0 % (19/20) in the patients who underwent R0 and R1 resection, respectively. The pathological high response rate was 70.0 % (14/20) and the pCR was 10.0 % (2/20). The regimen of induction SOX (S-1 + oxaliplatin) ± cetuximab chemotherapy followed by short-course chemoradiotherapy is safe and is associated with good tumor regression in patients with poor-risk locally advanced rectal cancer.

Assessing pathological complete response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer: a systematic review.

PubMed

Ryan, J E; Warrier, S K; Lynch, A C; Heriot, A G

2015-10-01

Pathological complete response to neoadjuvant chemoradiotherapy is found in 20% of patients with rectal cancer undergoing long-course chemoradiotherapy. Some authors have suggested that these patients do not need to undergo surgery and can be managed with careful follow-up, with surgery only used in the event of clinical failure. Widespread adoption of this regimen is limited by the accuracy of methods to confirm a pathological complete response (pCR). A systematic search of PubMed, Medline and Cochrane databases was conducted to identify clinical, histological and radiological features in those patients with rectal cancer who achieved a pCR following chemoradiotherapy. Searches were conducted with the following keywords and MeSH search terms: 'rectal neoplasm', 'response', 'neoadjuvant', 'preoperative chemoradiation' and 'tumour response'. After review of title and abstracts, 89 articles addressing the assessment of pCR were identified. Histology and clinical assessment are the most effective methods of assessment of pCR, with histology considered the gold standard. Clinical assessment is limited to low rectal tumours and is open to significant inter-rater variability, while histological examination requires a surgical specimen. Diffusion-weighted MRI and (18) F-fluorodeoxyglucose positron emission tomography/CT demonstrate the greatest potential for the assessment of pCR, but both modalities have limited accuracy. Determination of a pCR is crucial if a nonoperative approach is to be undertaken proactively. Various methods are available, but currently they lack sufficient sensitivity and specificity to define management. This is likely to be an area of further research in the future. Colorectal Disease © 2015 The Association of Coloproctology of Great Britain and Ireland.

Effectiveness of Radiotherapy in Myxoid Sarcomas Is Associated With a Dense Vascular Pattern

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

Vreeze, Ronald S.A. de; Jong, Daphne de; Haas, Rick L.

2008-12-01

Purpose: Surgery and adjuvant radiotherapy (RT) have long been the standard treatment for most deep-seated sarcomas; however, since the randomized trial from the National Cancer Institute of Canada, which described similar local control for pre- vs. postoperative RT, both modalities are now widely accepted. As a group, sarcomas are classified as radiation resistant. The subgroup of myxoid liposarcoma (MLS), a sarcoma with a typical vascular crow's feet pattern, is highly radiosensitive, but a mechanism for this phenomenon is unknown. Here we describe our results with preoperative RT and propose a mechanism explaining the high sensitivity based on the distinctive vascularizationmore » pattern of MLS. Methods and Materials: Between 2002 and 2006, 31 sarcoma patients, including 10 with MLS, underwent preoperative RT at our institute. Resected specimens were histologically evaluated, focusing on classification, grade, and vascularization patterns. Results: Twenty sarcomas showed more than 80% pathologic response after preoperative RT. A pathologic complete response was found in all 'pure' MLS specimens after preoperative RT (n = 8). There were no pathologic complete responses in the remaining sarcoma patients (n = 23), although 12 showed 80% to 90% pathologic response. In contrast to the remaining RT-resistant sarcomas, the highly responding specimens contained branching vasculature, partial thrombus formation and inflammation of medium sized arterioles, similar to the vascular changes in MLS. Conclusions: Both MLS and sarcomas with MLS-like vasculature are highly radiosensitive. Radiation sensitivity may be explained by changes in medium-sized arterioles, obstructing the specific crow's feet vascularization and inducing hypoxia with secondary tumor cell death.« less

Adaptive Randomization of Veliparib-Carboplatin Treatment in Breast Cancer.

PubMed

Rugo, Hope S; Olopade, Olufunmilayo I; DeMichele, Angela; Yau, Christina; van 't Veer, Laura J; Buxton, Meredith B; Hogarth, Michael; Hylton, Nola M; Paoloni, Melissa; Perlmutter, Jane; Symmans, W Fraser; Yee, Douglas; Chien, A Jo; Wallace, Anne M; Kaplan, Henry G; Boughey, Judy C; Haddad, Tufia C; Albain, Kathy S; Liu, Minetta C; Isaacs, Claudine; Khan, Qamar J; Lang, Julie E; Viscusi, Rebecca K; Pusztai, Lajos; Moulder, Stacy L; Chui, Stephen Y; Kemmer, Kathleen A; Elias, Anthony D; Edmiston, Kirsten K; Euhus, David M; Haley, Barbara B; Nanda, Rita; Northfelt, Donald W; Tripathy, Debasish; Wood, William C; Ewing, Cheryl; Schwab, Richard; Lyandres, Julia; Davis, Sarah E; Hirst, Gillian L; Sanil, Ashish; Berry, Donald A; Esserman, Laura J

2016-07-07

The genetic and clinical heterogeneity of breast cancer makes the identification of effective therapies challenging. We designed I-SPY 2, a phase 2, multicenter, adaptively randomized trial to screen multiple experimental regimens in combination with standard neoadjuvant chemotherapy for breast cancer. The goal is to match experimental regimens with responding cancer subtypes. We report results for veliparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, combined with carboplatin. In this ongoing trial, women are eligible for participation if they have stage II or III breast cancer with a tumor 2.5 cm or larger in diameter; cancers are categorized into eight biomarker subtypes on the basis of status with regard to human epidermal growth factor receptor 2 (HER2), hormone receptors, and a 70-gene assay. Patients undergo adaptive randomization within each biomarker subtype to receive regimens that have better performance than the standard therapy. Regimens are evaluated within 10 biomarker signatures (i.e., prospectively defined combinations of biomarker subtypes). Veliparib-carboplatin plus standard therapy was considered for HER2-negative tumors and was therefore evaluated in 3 signatures. The primary end point is pathological complete response. Tumor volume changes measured by magnetic resonance imaging during treatment are used to predict whether a patient will have a pathological complete response. Regimens move on from phase 2 if and when they have a high Bayesian predictive probability of success in a subsequent phase 3 neoadjuvant trial within the biomarker signature in which they performed well. With regard to triple-negative breast cancer, veliparib-carboplatin had an 88% predicted probability of success in a phase 3 trial. A total of 72 patients were randomly assigned to receive veliparib-carboplatin, and 44 patients were concurrently assigned to receive control therapy; at the completion of chemotherapy, the estimated rates of pathological complete response in the triple-negative population were 51% (95% Bayesian probability interval [PI], 36 to 66%) in the veliparib-carboplatin group versus 26% (95% PI, 9 to 43%) in the control group. The toxicity of veliparib-carboplatin was greater than that of the control. The process used in our trial showed that veliparib-carboplatin added to standard therapy resulted in higher rates of pathological complete response than standard therapy alone specifically in triple-negative breast cancer. (Funded by the QuantumLeap Healthcare Collaborative and others; I-SPY 2 TRIAL ClinicalTrials.gov number, NCT01042379.).

Standardized synoptic cancer pathology reports - so what and who cares? A population-based satisfaction survey of 970 pathologists, surgeons, and oncologists.

PubMed

Lankshear, Sara; Srigley, John; McGowan, Thomas; Yurcan, Marta; Sawka, Carol

2013-11-01

Cancer Care Ontario implemented synoptic pathology reporting across Ontario, impacting the practice of pathologists, surgeons, and medical and radiation oncologists. The benefits of standardized synoptic pathology reporting include enhanced completeness and improved consistency in comparison with narrative reports, with reported challenges including increased workload and report turnaround time. To determine the impact of synoptic pathology reporting on physician satisfaction specific to practice and process. A descriptive, cross-sectional design was utilized involving 970 clinicians across 27 hospitals. An 11-item survey was developed to obtain information regarding timeliness, completeness, clarity, and usability. Open-ended questions were also employed to obtain qualitative comments. A 51% response rate was obtained, with descriptive statistics reporting that physicians perceive synoptic reports as significantly better than narrative reports. Correlation analysis revealed a moderately strong, positive relationship between respondents' perceptions of overall satisfaction with the level of information provided and perceptions of completeness for clinical decision making (r = 0.750, P < .001) and ease of finding information for clinical decision making (r = 0.663, P < .001). Dependent t tests showed a statistically significant difference in the satisfaction scores of pathologists and oncologists (t169 = 3.044, P = .003). Qualitative comments revealed technology-related issues as the most frequently cited factor impacting timeliness of report completion. This study provides evidence of strong physician satisfaction with synoptic cancer pathology reporting as a clinical decision support tool in the diagnosis, prognosis, and treatment of cancer patients.

Neoadjuvant Bevacizumab, Oxaliplatin, 5-Fluorouracil, and Radiation for Rectal Cancer

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

Dipetrillo, Tom; Pricolo, Victor; Lagares-Garcia, Jorge

Purpose: To evaluate the feasibility and pathologic complete response rate of induction bevacizumab + modified infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) 6 regimen followed by concurrent bevacizumab, oxaliplatin, continuous infusion 5-fluorouracil (5-FU), and radiation for patients with rectal cancer. Methods and Materials: Eligible patients received 1 month of induction bevacizumab and mFOLFOX6. Patients then received 50.4 Gy of radiation and concurrent bevacizumab (5 mg/kg on Days 1, 15, and 29), oxaliplatin (50 mg/m{sup 2}/week for 6 weeks), and continuous infusion 5-FU (200 mg/m{sup 2}/day). Because of gastrointestinal toxicity, the oxaliplatin dose was reduced to 40 mg/m{sup 2}/week. Resection was performedmore » 4-8 weeks after the completion of chemoradiation. Results: The trial was terminated early because of toxicity after 26 eligible patients were treated. Only 1 patient had significant toxicity (arrhythmia) during induction treatment and was removed from the study. During chemoradiation, Grade 3/4 toxicity was experienced by 19 of 25 patients (76%). The most common Grade 3/4 toxicities were diarrhea, neutropenia, and pain. Five of 25 patients (20%) had a complete pathologic response. Nine of 25 patients (36%) developed postoperative complications including infection (n = 4), delayed healing (n = 3), leak/abscess (n = 2), sterile fluid collection (n = 2), ischemic colonic reservoir (n = 1), and fistula (n = 1). Conclusions: Concurrent oxaliplatin, bevacizumab, continuous infusion 5-FU, and radiation causes significant gastrointestinal toxicity. The pathologic complete response rate of this regimen was similar to other fluorouracil chemoradiation regimens. The high incidence of postoperative wound complications is concerning and consistent with other reports utilizing bevacizumab with chemoradiation before major surgical resections.« less

Phase II Trial of Induction Chemotherapy Followed by Surgery for Squamous Cell Carcinoma of the Oral Tongue in Young Adults

PubMed Central

Kies, Merrill S.; Boatright, Dowin H.; Li, Guojun; Blumenschein, George; El-Naggar, Adel K.; Lewin, Jan S.; Steinhaus, Ganene; Sturgis, Erich M.

2013-01-01

Background We conducted a phase II clinical trial of induction chemotherapy followed by surgery ± radiotherapy for squamous cell carcinoma of the oral tongue (SCCOT) in young adults. Methods From September 2001 to October 2004, 23 patients aged 18–49 years with clinical T2-3N0-2M0 SCCOT and no prior radiotherapy, chemotherapy, or neck dissection underwent induction chemotherapy (paclitaxel, ifosfamide, and carboplatin) followed by glossectomy and neck dissection ± radiotherapy and chemotherapy. Results On final surgical pathology, 9 (39%) patients had a complete/major (2 complete) histologic response at the primary tumor site; 8 (35%) had no response or progression. Similarly, 9 (39%) patients had a complete response in the neck or remained node negative; 6 (26%) had an increase in nodal category. No treatment-associated deaths occurred, and toxicity was modest. At a median follow-up from the end of treatment of 52 months (minimum, 23 months), 10 (43%) patients developed recurrence, and all 10 died of cancer. Crude recurrence/cancer death rates were associated with ≤ a partial response at the tongue (P = .029), poor histologic differentiation (P = .012), and multiple adverse features on final surgical pathology (P = .040). Conclusions Response rates and overall survival with this induction chemotherapy regimen were limited, but complete/major response at the tongue was associated with excellent prognosis. Additionally, improved patient selection and predictive tumor biomarkers will be needed for induction chemotherapy to be routinely incorporated into the treatment of oral tongue cancer in young adults. PMID:22009800

Phase II trial of induction chemotherapy followed by surgery for squamous cell carcinoma of the oral tongue in young adults.

PubMed

Kies, Merrill S; Boatright, Dowin H; Li, Guojun; Blumenschein, George; El-Naggar, Adel K; Brandon Gunn, G; Lewin, Jan S; Steinhaus, Ganene D; Sturgis, Erich M

2012-09-01

We conducted a phase II clinical trial of induction chemotherapy followed by surgery ± radiotherapy for squamous cell carcinoma of the oral tongue (SCCOT) in young adults. From September 2001 to October 2004, 23 patients aged 18 to 49 years with clinical T2-3 N0-2 M0 SCCOT and no prior radiotherapy, chemotherapy, or neck dissection underwent induction chemotherapy (paclitaxel, ifosfamide, and carboplatin) followed by glossectomy and neck dissection ± radiotherapy and chemotherapy. On final surgical pathology, 9 patients (39%) had a complete/major (2 complete) histologic response at the primary tumor site; 8 patients (35%) had no response or progression. Similarly, 9 patients (39%) had a complete response in the neck or remained node negative; 6 patients (26%) had an increase in nodal category. No treatment-associated deaths occurred, and toxicity was modest. At a median follow-up from the end of treatment of 52 months (minimum, 23 months), 10 patients (43%) developed recurrence, and all 10 died of cancer. Crude recurrence/cancer death rates were associated with ≤ a partial response at the tongue (p = .029), poor histologic differentiation (p = .012), and multiple adverse features on final surgical pathology (p = .040). Response rates and overall survival with this induction chemotherapy regimen were limited, but complete/major response at the tongue was associated with excellent prognosis. Additionally, improved patient selection and predictive tumor biomarkers will be needed for induction chemotherapy to be routinely incorporated into the treatment of oral tongue cancer in young adults. Copyright © 2011 Wiley Periodicals, Inc.

Predicting Response to Neoadjuvant Chemoradiotherapy in Esophageal Cancer with Textural Features Derived from Pretreatment 18F-FDG PET/CT Imaging.

PubMed

Beukinga, Roelof J; Hulshoff, Jan B; van Dijk, Lisanne V; Muijs, Christina T; Burgerhof, Johannes G M; Kats-Ugurlu, Gursah; Slart, Riemer H J A; Slump, Cornelis H; Mul, Véronique E M; Plukker, John Th M

2017-05-01

Adequate prediction of tumor response to neoadjuvant chemoradiotherapy (nCRT) in esophageal cancer (EC) patients is important in a more personalized treatment. The current best clinical method to predict pathologic complete response is SUV max in 18 F-FDG PET/CT imaging. To improve the prediction of response, we constructed a model to predict complete response to nCRT in EC based on pretreatment clinical parameters and 18 F-FDG PET/CT-derived textural features. Methods: From a prospectively maintained single-institution database, we reviewed 97 consecutive patients with locally advanced EC and a pretreatment 18 F-FDG PET/CT scan between 2009 and 2015. All patients were treated with nCRT (carboplatin/paclitaxel/41.4 Gy) followed by esophagectomy. We analyzed clinical, geometric, and pretreatment textural features extracted from both 18 F-FDG PET and CT. The current most accurate prediction model with SUV max as a predictor variable was compared with 6 different response prediction models constructed using least absolute shrinkage and selection operator regularized logistic regression. Internal validation was performed to estimate the model's performances. Pathologic response was defined as complete versus incomplete response (Mandard tumor regression grade system 1 vs. 2-5). Results: Pathologic examination revealed 19 (19.6%) complete and 78 (80.4%) incomplete responders. Least absolute shrinkage and selection operator regularization selected the clinical parameters: histologic type and clinical T stage, the 18 F-FDG PET-derived textural feature long run low gray level emphasis, and the CT-derived textural feature run percentage. Introducing these variables to a logistic regression analysis showed areas under the receiver-operating-characteristic curve (AUCs) of 0.78 compared with 0.58 in the SUV max model. The discrimination slopes were 0.17 compared with 0.01, respectively. After internal validation, the AUCs decreased to 0.74 and 0.54, respectively. Conclusion: The predictive values of the constructed models were superior to the standard method (SUV max ). These results can be considered as an initial step in predicting tumor response to nCRT in locally advanced EC. Further research in refining the predictive value of these models is needed to justify omission of surgery. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

The efficacy and safety of neoadjuvant chemotherapy +/- letrozole in postmenopausal women with locally advanced breast cancer: a randomized phase III clinical trial.

PubMed

Mohammadianpanah, Mohammad; Ashouri, Yaghoub; Hoseini, Sare; Amadloo, Niloofar; Talei, Abdolrasoul; Tahmasebi, Sedigheh; Nasrolahi, Hamid; Mosalaei, Ahmad; Omidvari, Shapour; Ansari, Mansour; Mosleh-Shirazi, Mohammad Amin

2012-04-01

This two-arm randomized clinical study aimed to evaluate the efficacy and safety of neoadjuvant concurrent chemotherapy and letrozole in postmenopausal women with locally advanced breast carcinoma. One hundred and one postmenopausal women aged 50-83 years with pathologically proven locally advanced (clinical stage T3, T4 and/or N2, N3) breast cancer were randomly assigned to receive neoadjuvant chemotherapy alone (control arm, n = 51) or neoadjuvant chemotherapy concurrent with letrozole 2.5 mg (study arm, n = 50). Chemotherapy consisted of a median 4 (range 3-5) cycles of intravenous 5-fluorouracil 600 mg/m(2), doxorubicin 60 mg/m(2), and cyclophosphamide 600 mg/m(2), every three weeks. All patients subsequently underwent modified radical mastectomy approximately two weeks after the last cycle of chemotherapy. Pathologic complete response rates were 25.5% and 10.2% in the study and the control group, respectively (P = 0.049). Similarly, clinical complete response rates were 27.6% and 10.2% in the study and the control group, respectively (P = 0.037). In the subgroup analysis of hormone receptor-positive cases, the complete response rates were more prominent in study group compared with control group. Common treatment-related side effects such as nausea, vomiting, bone marrow suppression, and mucositis were similar in both groups, but hot flush was more prevalent in study group compared with control group (P = 0.023). The addition of letrozole concurrently with neoadjuvant chemotherapy provides a higher clinical and pathologic response rates with acceptable toxicity compared with chemotherapy alone in postmenopausal women with locally advanced sensitive breast cancer.

Predictive factors in the evaluation of treatment response to neoadjuvant chemoradiotherapy in patients with advanced esophageal squamous cell cancer

PubMed Central

Wong, Claudia

2017-01-01

Neoadjuvant therapy before esophagectomy is evidence-based, and is a standard-of-care for locally advanced and operable esophageal cancer. However response to such treatment varies in individual patients, from no clinical response to pathological complete response. It has been consistently shown that a good pathological responses is of prognostic value, but perhaps in the expense of those who do not. It is important to identify suitable predictive factors for response, so that patients are not exposed to potentially harmful chemotherapy and/or radiotherapy without benefits. Alternative management strategies can be devised. Various clinical, radiological, serological and potential molecular markers have been studied. None has been shown to be sufficiently reliable to be used in daily practice. Certainly more understanding of the molecular basis for response to chemotherapy/radiotherapy is needed, so that patient treatment can be tailored and individualized. PMID:28815073

Contrast-Enhanced Spectral Mammography is Comparable to MRI in the Assessment of Residual Breast Cancer Following Neoadjuvant Systemic Therapy.

PubMed

Patel, Bhavika K; Hilal, Talal; Covington, Matthew; Zhang, Nan; Kosiorek, Heidi E; Lobbes, Marc; Northfelt, Donald W; Pockaj, Barbara A

2018-05-01

To evaluate the performance of contrast-enhanced spectral mammography (CESM) compared to MRI in the assessment of tumor response in breast cancer patients undergoing neoadjuvant systemic therapy (NST). The institutional review board approved this study. From September 2014 to June 2017, we identified patients with pathologically confirmed invasive breast cancer who underwent NST. All patients had both CESM and MRI performed pre- and post-NST with pathological assessment after surgical management. Size of residual malignancy on post-NST CESM and MRI was compared with surgical pathology. Lin concordance and Pearson correlation coefficient were used to assess agreement. Bland-Altman plots were used to visualize the differences between tumor size on imaging and pathology. Sixty-five patients were identified. Mean age was 52.7 (range 30-76) years. Type of NST included chemotherapy in 53 (82%) and endocrine therapy in 12 (18%). Mean tumor size after NST was 14.6 (range 0-105) mm for CESM and 14.2 mm (range 0-75 mm) for MRI compared with 19.6 (range 0-100) mm on final surgical pathology. Equivalence tests demonstrated that mean tumor size measured by CESM (p = 0.009) or by MRI (p = 0.01) was equivalent to the mean tumor size measured by pathology within - 1 and 1-cm range. Comparing CESM versus MRI for assessment of complete response, the sensitivity was 95% versus 95%, specificity 66.7% versus 68.9%, positive predictive value 55.9% versus 57.6%, and negative predictive value 96.7% versus 96.9% respectively. CESM was comparable to MRI in assessing residual malignancy after completion of NST.

Predicting pathological complete response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer: a systematic review.

PubMed

Ryan, J E; Warrier, S K; Lynch, A C; Ramsay, R G; Phillips, W A; Heriot, A G

2016-03-01

Approximately 20% of patients treated with neoadjuvant chemoradiotherapy (nCRT) for locally advanced rectal cancer achieve a pathological complete response (pCR) while the remainder derive the benefit of improved local control and downstaging and a small proportion show a minimal response. The ability to predict which patients will benefit would allow for improved patient stratification directing therapy to those who are likely to achieve a good response, thereby avoiding ineffective treatment in those unlikely to benefit. A systematic review of the English language literature was conducted to identify pathological factors, imaging modalities and molecular factors that predict pCR following chemoradiotherapy. PubMed, MEDLINE and Cochrane Database searches were conducted with the following keywords and MeSH search terms: 'rectal neoplasm', 'response', 'neoadjuvant', 'preoperative chemoradiation', 'tumor response'. After review of title and abstracts, 85 articles addressing the prediction of pCR were selected. Clear methods to predict pCR before chemoradiotherapy have not been defined. Clinical and radiological features of the primary cancer have limited ability to predict response. Molecular profiling holds the greatest potential to predict pCR but adoption of this technology will require greater concordance between cohorts for the biomarkers currently under investigation. At present no robust markers of the prediction of pCR have been identified and the topic remains an area for future research. This review critically evaluates existing literature providing an overview of the methods currently available to predict pCR to nCRT for locally advanced rectal cancer. The review also provides a comprehensive comparison of the accuracy of each modality. Colorectal Disease © 2015 The Association of Coloproctology of Great Britain and Ireland.

Neoadjuvant paclitaxel poliglumex, cisplatin, and radiation for esophageal cancer: a phase 2 trial.

PubMed

Dipetrillo, Thomas; Suntharalingam, Mohan; Ng, Thomas; Fontaine, Jacques; Horiba, Naomi; Oldenburg, Nicklas; Perez, Kimberly; Birnbaum, Ari; Battafarano, Richard; Burrows, Whitney; Safran, Howard

2012-02-01

To evaluate the pathologic complete response (CR) rate and safety of paclitaxel poliglumex (PPX), cisplatin, and concurrent radiation for patients with esophageal cancer. Patients with adenocarcinoma or squamous cell carcinoma of the esophagus or gastroesophageal junction with no evidence of distant metastasis received PPX (50 mg/m(2)/wk) and cisplatin (25 mg/m(2)/wk) for 6 weeks with 50.4 Gy concurrent radiation. Six to eight weeks after completion of chemoradiotherapy, patients underwent surgical resection. Forty patients were enrolled, 37 patients with adenocarcinoma and 3 patients with squamous cell cancer. The treatment-related grade 3 nonhematologic toxicities included esophagitis (7%), nausea (7%), and fatigue (5%). Three patients with clinical endoscopic CR (2 with squamous cell cancer) refused surgery. Twelve of the remaining 37 patients (32%) had a pathologic CR. The 12 patients with pathologic CR all had adenocarcinoma. PPX, cisplatin, and concurrent radiation are well tolerated, easily administered regimen for esophageal cancer with a low incidence of significant esophagitis and a high pathologic CR rate consistent with the preclinical data of PPX and radiation.

A Survey of Attitudes of Board-Certified Veterinary Pathologists to Forensic Veterinary Pathology.

PubMed

McEwen, B J; McDonough, S P

2016-09-01

An electronic survey was conducted to determine the attitudes of veterinary pathologists toward forensic pathology and the adequacy of their training in the discipline. The survey was sent to 1933 diplomates of the American College of Veterinary Pathologists and 311 completed responses were analyzed. Of respondents, 80% report receiving at least 1 type of medicolegal case, with cases from law enforcement received most frequently. Most (74%) of the respondents indicated that their previous training did not prepare them adequately to handle forensic cases and almost half of the respondents (48%) indicated that they needed more training on serving as an expert witness. Relative risk ratios (RRR) and odds ratios (OR) were generated to determine the strength of a statistically significant association. Responses from a free-text entry question determining additional training needs could be grouped into 3 main categories: (1) veterinary forensic pathology science and procedures, (2) documentation, evidence collection and handling, and (3) knowledge of the medicolegal system. Last, a field for additional comments or suggestions regarding veterinary forensic pathology was completed by 107 respondents and many reinforced the need for training in the categories previously described. The survey highlights that a significant proportion of diplomates of the American College of Veterinary Pathologists are currently engaged in veterinary forensic pathology but feel their training has not adequately prepared them for these cases. Hopefully, the survey results will inform the college and residency training coordinators as they address the training requirements for an important emerging discipline. © The Author(s) 2016.

Nottingham Clinico-Pathological Response Index (NPRI) after neoadjuvant chemotherapy (Neo-ACT) accurately predicts clinical outcome in locally advanced breast cancer.

PubMed

Abdel-Fatah, Tarek M; Ball, Graham; Lee, Andrew H S; Pinder, Sarah; MacMilan, R Douglas; Cornford, Eleanor; Moseley, Paul M; Silverman, Rafael; Price, James; Latham, Bruce; Palmer, David; Chan, Arlene; Ellis, Ian O; Chan, Stephen Y T

2015-03-01

There is a need to identify more sensitive clinicopathologic criteria to assess the response to neoadjuvant chemotherapy (Neo-ACT) and guide subsequent adjuvant therapy. We performed a clinicopathologic assessment of 426 patients who had completed Neo-ACT for locally advanced breast cancer (LABC) with a median follow-up of 70 months. Patients were divided into a training set treated with anthracycline combination chemotherapy (n = 172); an internal validation set treated with anthracycline and taxane (n = 129); and an external validation set treated with anthracycline with or without taxane (n = 125). A multivariate Cox regression model demonstrated the absence of fibrosis, presence of lymphovascular invasion, increasing number of lymph node metastases, and administration of hormone therapy were significantly associated with short breast cancer-specific survival (BCSS) and disease-free survival (DFS); Ps < 0.01, while reduction of tumor size was associated with DFS (P = 0.022). Nottingham Clinico-Pathological Response Indexes (NPRI) were calculated, and four prognostic groups (NPRI-PG) were identified. Patients in prognostic group 2 (NPRI-PG2) for BCSS (66 of 172; 38.4%) have the same prognosis as those who achieved pathologic complete response (pCR; NPRI-PG1; 15%). Receiver-operating characteristic (ROC) curves indicated that the NPRI outperformed the currently used prognostic factors and adding the NPRI improved their performance as a predictor for both BCSS (area under the curve [AUC], 0.88) and DFS (AUC, 0.87). The NPRI predicts BCSS and DFS, with a higher sensitivity than pCR. The NPRI can also improve the sensitivity and specificity of clinicopathologic response as a study endpoint, for assessing response to Neo-ACT, and can serve as a valuable tool for the discovery of future predictive molecular markers. ©2014 American Association for Cancer Research.

Extended Survival after Complete Pathological Response in Metastatic Pancreatic Ductal Adenocarcinoma Following Induction Chemotherapy, Chemoradiotherapy, and a Novel Immunotherapy Agent, IMM-101

PubMed Central

Giakoustidis, Alex; Stamp, Gordon; Gaya, Andy; Mudan, Satvinder

2015-01-01

Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor prognosis. Median survival for metastatic patients is six to nine months and survivors beyond one year are exceptional. Pancreatic cancer is resistant to conventional chemotherapy and is often diagnosed at advanced stages. However, immunotherapy is a rapidly advancing new treatment modality, which shows promise in many solid tumor types.​ We present a patient with metastatic pancreatic cancer who underwent a synchronous resection of the primary tumour (pancreatoduodenectomy) and metastatic site (left hepatectomy) after multimodality neoadjuvant treatment with gemcitabine, nab-paclitaxel, and immunotherapy backbone with IMM-101 (an intradermally applied immunomodulator), as well as consolidation chemoradiation. Pathology of the specimens showed a complete response in both sites of the disease. The patient remains alive four years from the initial diagnosis and continues on maintenance immunotherapy. This exceptional response to initial chemo-immunotherapy was followed by a novel and off-protocol approach of low-dose capecitabine and IMM-101 as a maintenance strategy. The survival benefit and sustained performance status could set this as a new paradigm for the treatment of oligometastatic pancreatic cancer following response to systemic therapy and immunotherapy.​ PMID:26870619

Cue-induced craving in pathological buying: empirical evidence and clinical implications.

PubMed

Trotzke, Patrick; Starcke, Katrin; Pedersen, Anya; Brand, Matthias

2014-01-01

Pathological buying is associated with marked distress and impaired functioning in important life domains. It is currently under debate whether pathological buying can be considered a behavioral addiction. In analogy to results reported in addicted individuals, craving reactions elicited by addiction-related cues might be an underlying mechanism for the etiology and pathogenesis of pathological buying. In the present study, 30 pathological buyers and 30 matched control participants were examined with a cue-reactivity paradigm consisting of shopping and control cues. Skin conductance responses, as well as subjective ratings for arousal, valence, and urge to buy, were assessed. Subjective craving reactions were measured before and after the cue-reactivity paradigm. On a physiological level, skin conductance responses toward shopping cues were higher in pathological buyers (mean [M; standard deviation {SD}] = 0.26 [0.13]) compared with control participants (M [SD] = 0.19 [0.09]; t(58) = 2.29, p = .025, d = 0.60). On a behavioral level, the individuals with pathological buying rated the shopping cues as more arousing and more positive, and reported a greater urge to buy compared with control participants and with control cues. An increase in subjective craving after completing the cue-reactivity paradigm was observed only in the pathological buyers (Mpre [SD] = 1.95 [1.47], Mpost [SD] = 2.87 [1.79]; t(29) = 5.07, p < .001, d = 0.97). Cue-reactivity and craving might be potential correlates for the development and maintenance of pathological buying. The results demonstrate similarities between pathological buying and substance or behavioral addictions and provide implications for clinical treatment.

A Specific miRNA Signature Correlates With Complete Pathological Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer

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

Della Vittoria Scarpati, Giuseppina; Falcetta, Francesca; Carlomagno, Chiara, E-mail: chiara.carlomagno@unina.it

2012-07-15

Purpose: MicroRNAs (miRNAs) are small, noncoding RNA molecules that can be down- or upregulated in colorectal cancer and have been associated to prognosis and response to treatment. We studied miRNA expression in tumor biopsies of patients with rectal cancer to identify a specific 'signature' correlating with pathological complete response (pCR) after neoadjuvant chemoradiotherapy. Methods and Materials: A total of 38 T3-4/N+ rectal cancer patients received capecitabine-oxaliplatin and radiotherapy followed by surgery. Pathologic response was scored according to the Mandard TRG scale. MiRNA expression was analyzed by microarray and confirmed by real-time Reverse Transcription Polymerase Chain Reaction (qRT-PCR) on frozen biopsiesmore » obtained before treatment. The correlation between miRNA expression and TRG, coded as TRG1 (pCR) vs. TRG >1 (no pCR), was assessed by methods specifically designed for this study. Results: Microarray analysis selected 14 miRNAs as being differentially expressed in TRG1 patients, and 13 were confirmed by qRT-PCR: 11 miRNAs (miR-1183, miR-483-5p, miR-622, miR-125a-3p, miR-1224-5p, miR-188-5p, miR-1471, miR-671-5p, miR-1909 Asterisk-Operator , miR-630, miR-765) were significantly upregulated in TRG1 patients, 2 (miR-1274b, miR-720) were downexpressed. MiR-622 and miR-630 had a 100% sensitivity and specificity in selecting TRG1 cases. Conclusions: A set of 13 miRNAs is strongly associated with pCR and may represent a specific predictor of response to chemoradiotherapy in rectal cancer patients.« less

Phase II study of capecitabine (Xeloda (registered) ) and concomitant boost radiotherapy in patients with locally advanced rectal cancer

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

Krishnan, Sunil; Janjan, Nora A.; Skibber, John M.

2006-11-01

Purpose: The aim of this study was to determine the efficacy of capecitabine (Xeloda (registered) ), an oral fluoropyrimidine, as a radiosensitizer in the neoadjuvant treatment of locally advanced rectal cancer (LARC). Methods and Materials: We conducted a phase II study of capecitabine (825 mg/m{sup 2} orally, twice daily continuous) with radiotherapy (52.5 Gy/30 fractions to the primary tumor and perirectal nodes) in 54 patients with LARC (node-negative {>=}T3 or any node-positive tumor) staged by endoscopic ultrasound (EUS). The primary endpoint was pathologic response rate; secondary endpoints included toxicity profiles and survival parameters. Results: Of the 54 patients (median age,more » 56.7 years; range, 21.3-78.7 years; male:female ratio, 1.7; Eastern Cooperative Oncology Group performance status 0-1: 100%), 51 patients (94%) had T3N0 or T3N1 disease by EUS. Surgery was not performed in 3 patients; 2 of these patients had metastatic disease, and the third patient refused after a complete clinical response. Of the 51 patients evaluable for pathologic response, 9 patients (18%) achieved complete response, and 12 patients (24%) had microscopic residual disease (<10% viable cells). In addition, 26 patients of all 54 patients (51%) achieved T-downstaging, and 15 patients of 29 patients (52%) achieved N-downstaging. Grade 3/4 toxicities were radiation dermatitis (9%) and diarrhea (2%). Sphincter preservation rate for tumor {<=}5 cm from the anal verge was 67% (18/27). Conclusion: This regimen of radiotherapy plus capecitabine is well tolerated and is more convenient than protracted venous infusion of 5-FU. The pathologic response rate is comparable to our previous experience using protracted venous infusion 5-FU for LARC.« less

High Proliferation Predicts Pathological Complete Response to Neoadjuvant Chemotherapy in Early Breast Cancer

PubMed Central

Lluch, Ana; Ribelles, Nuria; Anton-Torres, Antonio; Sanchez-Rovira, Pedro; Albanell, Joan; Calvo, Lourdes; García-Asenjo, Jose Antonio Lopez; Palacios, Jose; Chacon, Jose Ignacio; Ruiz, Amparo; De la Haba-Rodriguez, Juan; Segui-Palmer, Miguel A.; Cirauqui, Beatriz; Margeli, Mireia; Plazaola, Arrate; Barnadas, Agusti; Casas, Maribel; Caballero, Rosalia; Carrasco, Eva; Rojo, Federico

2016-01-01

Background. In the neoadjuvant setting, changes in the proliferation marker Ki67 are associated with primary endocrine treatment efficacy, but its value as a predictor of response to chemotherapy is still controversial. Patients and Methods. We analyzed 262 patients with centralized basal Ki67 immunohistochemical evaluation derived from 4 GEICAM (Spanish Breast Cancer Group) clinical trials of neoadjuvant chemotherapy for breast cancer. The objective was to identify the optimal threshold for Ki67 using the receiver-operating characteristic curve method to maximize its predictive value for chemotherapy benefit. We also evaluated the predictive role of the defined Ki67 cutoffs for molecular subtypes defined by estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2). Results. A basal Ki67 cutpoint of 50% predicted pathological complete response (pCR). Patients with Ki67 >50% achieved a pCR rate of 40% (36 of 91) versus a pCR rate of 19% in patients with Ki67 ≤50% (33 of 171) (p = .0004). Ki67 predictive value was especially relevant in ER-HER2− and ER-HER2+ patients (pCR rates of 42% and 64%, respectively, in patients with Ki67 >50% versus 15% and 45%, respectively, in patients with Ki67 ≤50%; p = .0337 and .3238, respectively). Both multivariate analyses confirmed the independent predictive value of the Ki67 cutpoint of 50%. Conclusion. Basal Ki67 proliferation index >50% should be considered an independent predictive factor for pCR reached after neoadjuvant chemotherapy, suggesting that cell proliferation is a phenomenon closely related to chemosensitivity. These findings could help to identify a group of patients with a potentially favorable long-term prognosis. Implications for Practice: The use of basal Ki67 status as a predictive factor of chemotherapy benefit could facilitate the identification of a patient subpopulation with high probability of achieving pathological complete response when treated with primary chemotherapy, and thus with a potentially favorable long-term prognosis. PMID:26786263

Modern Outcomes of Inflammatory Breast Cancer

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

Rehman, Sana; Northeast Ohio Medical University, Rootstown, Ohio; Reddy, Chandana A.

2012-11-01

Purpose: To report contemporary outcomes for inflammatory breast cancer (IBC) patients treated in the modern era of trastuzumab and taxane-based chemotherapy. Methods and Materials: We retrospectively reviewed the charts of 104 patients with nonmetastatic IBC treated between January 2000 and December 2009. Patients who received chemotherapy, surgery, and radiation therapy were considered to have completed the intended therapy. Kaplan-Meier curves estimated locoregional control (LRC), distant metastases-free survival (DMFS), and overall survival. Results: The median follow-up time was 34 months; 57 (55%) patients were estrogen receptor progesterone receptor (ER/PR) negative, 34 (33%) patients were human epidermal growth factor receptor 2 (her2)/neumore » amplified, and 78 (75%) received definitive postoperative radiation. Seventy-five (72%) patients completed all of the intended therapy, of whom 67 (89%) received a taxane and 18/28 (64%) of her2/neu-amplified patients received trastuzumab. For the entire cohort, the 5-year rates of overall survival, LRC, and DMFS were 46%, 83%, and 44%, respectively. The ER/PR-negative patients had a 5-year DMFS of 39% vs. 52% for ER/PR-positive patients (p = 0.03). The 5-year DMFS for patients who achieved a pathologic complete response compared with those who did not was 83% vs. 44% (p < 0.01). Those patients who received >60.4 Gy (n = 15) to the chest wall had a 5-year LRC rate of 100% vs. 83% for those who received 45 to 60.4 Gy (n = 49; p = 0.048). On univariate analysis, significant predictors of DMFS included achieving a complete response to neoadjuvant chemotherapy (hazard ratio [HR] = 5.8; 95% confidence interval [CI] = 1.4-24.4; p = 0.02) and pathologically negative lymph nodes (HR = 4.1; 95% CI = 1.4-11.9; p < 0.01), but no factor was significant on multivariate analysis. Conclusions: For IBC patients, the rate of distant metastases is still high despite excellent local control, particularly for patients who received >60.4 Gy to the chest wall. Despite the use of taxanes and trastuzumab, outcomes remain modest, particularly for those with ER/PR-negative disease and those without a pathologic complete response.« less

Role of Stereotactic Body Radiation Therapy Before Orthotopic Liver Transplantation: Retrospective Evaluation of Pathologic Response and Outcomes

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

Mannina, Edward Michael, E-mail: emmannina@gmail.com; Cardenes, Higinia Rosa; Lasley, Foster D.

Purpose: To analyze the results of stereotactic body radiation therapy (SBRT) in patients with early-stage, localized hepatocellular carcinoma who underwent definitive orthotopic liver transplantation (OLT). Methods and Materials: The subjects of this retrospective report are 38 patients diagnosed with hepatocellular carcinoma who underwent SBRT per institutional phase 1 to 2 eligibility criteria, before definitive OLT. Pre-OLT radiographs were compared with pathologic gold standard. Analysis of treatment failures and deaths was undertaken. Results: With median follow-up of 4.8 years from OLT, 9 of 38 patients (24%) recurred, whereas 10 of 38 patients (26%) died. Kaplan-Meier estimates of 3-year overall survival and disease-free survivalmore » are 77% and 74%, respectively. Sum longest dimension of tumors was significantly associated with disease-free survival (hazard ratio 1.93, P=.026). Pathologic response rate (complete plus partial response) was 68%. Radiographic scoring criteria performed poorly; modified Response Evaluation Criteria in Solid Tumors produced highest concordance (κ = 0.224). Explants revealed viable tumor in 74% of evaluable patients. Treatment failures had statistically larger sum longest dimension of tumors (4.0 cm vs 2.8 cm, P=.014) and non–statistically significant higher rates of lymphovascular space invasion (44% vs 17%), cT2 disease (44% vs 21%), ≥pT2 disease (67% vs 34%), multifocal tumors at time of SBRT (44% vs 21%), and less robust mean α-fetoprotein response (−25 IU/mL vs −162 IU/mL). Conclusions: Stereotactic body radiation therapy before to OLT is a well-tolerated treatment providing 68% pathologic response, though 74% of explants ultimately contained viable tumor. Radiographic response criteria poorly approximate pathology. Our data suggest further stratification of patients according to initial disease burden and treatment response.« less

Efficacy of neoadjuvant bevacizumab added to docetaxel followed by fluorouracil, epirubicin, and cyclophosphamide, for women with HER2-negative early breast cancer (ARTemis): an open-label, randomised, phase 3 trial.

PubMed

Earl, Helena M; Hiller, Louise; Dunn, Janet A; Blenkinsop, Clare; Grybowicz, Louise; Vallier, Anne-Laure; Abraham, Jean; Thomas, Jeremy; Provenzano, Elena; Hughes-Davies, Luke; Gounaris, Ioannis; McAdam, Karen; Chan, Stephen; Ahmad, Rizvana; Hickish, Tamas; Houston, Stephen; Rea, Daniel; Bartlett, John; Caldas, Carlos; Cameron, David A; Hayward, Larry

2015-06-01

The ARTemis trial was developed to assess the efficacy and safety of adding bevacizumab to standard neoadjuvant chemotherapy in HER2-negative early breast cancer. In this randomised, open-label, phase 3 trial, we enrolled women (≥18 years) with newly diagnosed HER2-negative early invasive breast cancer (radiological tumour size >20 mm, with or without axillary involvement), at 66 centres in the UK. Patients were randomly assigned via a central computerised minimisation procedure to three cycles of docetaxel (100 mg/m(2) once every 21 days) followed by three cycles of fluorouracil (500 mg/m(2)), epirubicin (100 mg/m(2)), and cyclophosphamide (500 mg/m(2)) once every 21 days (D-FEC), without or with four cycles of bevacizumab (15 mg/kg) (Bev+D-FEC). The primary endpoint was pathological complete response, defined as the absence of invasive disease in the breast and axillary lymph nodes, analysed by intention to treat. The trial has completed and follow-up is ongoing. This trial is registered with EudraCT (2008-002322-11), ISRCTN (68502941), and ClinicalTrials.gov (NCT01093235). Between May 7, 2009, and Jan 9, 2013, we randomly allocated 800 participants to D-FEC (n=401) and Bev+D-FEC (n=399). 781 patients were available for the primary endpoint analysis. Significantly more patients in the bevacizumab group achieved a pathological complete response compared with those treated with chemotherapy alone: 87 (22%, 95% CI 18-27) of 388 patients in the Bev+D-FEC group compared with 66 (17%, 13-21) of 393 patients in the D-FEC group (p=0·03). Grade 3 and 4 toxicities were reported at expected levels in both groups, although more patients had grade 4 neutropenia in the Bev+D-FEC group than in the D-FEC group (85 [22%] vs 68 [17%]). Addition of four cycles of bevacizumab to D-FEC in HER2-negative early breast cancer significantly improved pathological complete response. However, whether the improvement in pathological complete response will lead to improved disease-free and overall survival outcomes is unknown and will be reported after longer follow-up. Meta-analysis of available neoadjuvant trials is likely to be the only way to define subgroups of early breast cancer that would have clinically significant long-term benefit from bevacizumab treatment. Cancer Research UK, Roche, Sanofi-Aventis. Copyright © 2015 Earl et al. Open Access article distributed under the terms of CC BY-NC-ND. Published by Elsevier Ltd.. All rights reserved.

Activity of thalidomide and capecitabine in patients with advanced hepatocellular carcinoma.

PubMed

Ang, Soo-Fan; Tan, Sze-Huey; Toh, Han-Chong; Poon, Donald Y H; Ong, Simon Y K; Foo, Kian-Fong; Choo, Su-Pin

2012-06-01

Thalidomide has shown modest activity in advanced hepatocellular carcinomas (HCCs). Single-agent capecitabine has also been used in patients with HCC, with objective responses being reported. In our study, we review the use of thalidomide and capecitabine combination in advanced HCC. From November 2003 and September 2008, 42 patients with advanced HCC who were not eligible for clinical trial or conventional chemotherapy were treated with oral capecitabine (2000 mg/m/d) for 14 days every 3 weeks and oral thalidomide at the doses of 50 to 200 mg/d. Almost 50% of patients had Child-Pugh B or C liver cirrhosis and a history of regional or systemic therapy. Three patients achieved complete responses lasting more than 52 weeks, including 1 patient who achieved pathological complete response and underwent curative resection. There were 3 patients with partial responses and 13 with stable disease. Median overall survival of all 42 patients was 9.9 months. The median progression-free survival was 5.1 months. The presence of ascites, portal vein thrombosis, and poorer Child-Pugh liver cirrhosis status also resulted in significantly poorer survival outcome. Treatment was well tolerated. Fatigue was the most common side effect occurring in 16 (38%) patients, but only 1 patient had grade 3 toxicity and had to stop treatment. Two other patients developed grade 3 palmar-plantar erythrodysesthesia from capecitabine. The combination of thalidomide and capecitabine has activity in advanced HCC and can result in complete pathological response. Treatment is well tolerated even in less-fit patients who have been pretreated and deserve further study.

Prognostic significance of pathological response of primary tumor and metastatic axillary lymph nodes after neoadjuvant chemotherapy for locally advanced breast carcinoma.

PubMed

Machiavelli, M R; Romero, A O; Pérez, J E; Lacava, J A; Domínguez, M E; Rodríguez, R; Barbieri, M R; Romero Acuña, L A; Romero Acuña, J M; Langhi, M J; Amato, S; Ortiz, E H; Vallejo, C T; Leone, B A

1998-01-01

The prognostic significance of pathological response of primary tumor and metastatic axillary lymph nodes after neoadjuvant chemotherapy was assessed in patients with noninflammatory locally advanced breast carcinoma. Between January 1989 and April 1995, 148 consecutive patients with locally advanced breast carcinoma participated in the study. Of these, 140 fully evaluable patients (67, stage IIIA; 73, stage IIIB) were treated with three courses of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC), followed by modified radical mastectomy when technically feasible or definitive radiation therapy. The median age was 53 years (range, 26 to 75 years); 55% of patients were postmenopausal. Objective response was recorded in 99 of 140 patients (71%; 95% confidence interval, 63% to 79%). Complete response occurred in 11 patients (8%), and partial response occurred in 88 patients (63%). No change was recorded in 37 patients (26%), and progressive disease occurred in 4 patients (3%). One hundred and thirty-six patients underwent the planned surgery. Maximal pathological response of the primary tumor (in situ carcinoma or minimal microscopic residual tumor) was observed in 24 (18%); 112 patients (82%) presented minimal pathological response of the primary tumor (gross residual tumor). The number of metastatic axillary nodes after neoadjuvant chemotherapy was as follows: N0, 39 patients (29%); N1-N3, 35 patients (26%); > N3, 62 patients (45%). Considering the initial TNM status, 75% of the patients had decreases in tumor compartment after neoadjuvant chemotherapy. Also, 31% and 23% of patients with clinical N1 and N2, respectively, showed uninvolved axillary lymph nodes. A significant correlation was noted between pathological response of primary tumor and the number of metastatic axillary lymph nodes. Median disease-free survival was 34 months, whereas median overall survival was 66 months. Pathological responses of both primary tumor and metastatic axillary lymph nodes were strongly correlated with disease-free survival and overall survival in univariate analyses. Additionally, in a proportional hazard regression model and in an accelerated failure time model, metastatic axillary lymph nodes significantly influenced both disease-free survival and overall survival, whereas pathological response of primary tumor did so on disease-free survival only. After neoadjuvant chemotherapy, pathological responses of both primary tumor and metastatic axillary lymph nodes had a marked prognostic significance and influenced outcome for patients with locally advanced breast carcinoma. Our results suggest that maximal tumor shrinkage and sterilization of potentially involved axillary nodes may represent a major goal of neoadjuvant chemotherapy. Further studies are warranted to clarify whether these results reflect the therapeutic effect or intrinsic biologic factors of the tumor.

Long-term survival based on pathologic response to neoadjuvant therapy in esophageal cancer.

PubMed

Tiesi, Gregory; Park, Wungki; Gunder, Meredith; Rubio, Gustavo; Berger, Michael; Ardalan, Bach; Livingstone, Alan; Franceschi, Dido

2017-08-01

Neoadjuvant treatment is standard for locally advanced esophageal cancer. However, whether the addition of radiation to neoadjuvant regimen improves survival remains unclear. The aim of this study was to compare survival in locally advanced esophageal cancer treated with neoadjuvant chemotherapy versus chemoradiation. A prospectively maintained database of esophagectomies (1999-2012) was analyzed. We identified 297 patients with locally advanced esophageal cancer that underwent either neoadjuvant chemotherapy (n = 231) or chemoradiation (n = 66) followed by esophagectomy. Pretreatment and pathologic staging were compared to assess response. Overall survival was recorded. Most patients in the chemotherapy and chemoradiation groups had pretreatment stage III disease (66.7% versus 65.2%; P = 0.44). Median follow-up was 79.3 and 64.9 mo for chemotherapy and chemoradiation cohorts, respectively. Complete response rate was higher in chemoradiation than chemotherapy groups (30.3% versus 13.8%; P < 0.001). Overall survival was similar between complete responders in both groups (median not reached versus 121.1 mo; chemotherapy versus chemoradiation). However, partial responders in the chemotherapy cohort had improved median survival (147.2 mo) versus those in the chemoradiation cohort (83.7 mo, P < 0.03). Within the chemotherapy-only group, partial responders had improved survival compared with nonresponders (P = 0.041); however, there was no difference in survival between partial and complete responders (P = 0.36). In patients undergoing esophagectomy for locally advanced esophageal cancer, neoadjuvant chemotherapy was associated with an equivalent overall survival, when compared with neoadjuvant chemoradiotherapy. Adding neoadjuvant radiation may enhance complete response rates but does not appear to be associated with improved survival. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of MR Imaging Contrast Thresholds on Prediction of Neoadjuvant Chemotherapy Response in Breast Cancer Subtypes: A Subgroup Analysis of the ACRIN 6657/I-SPY 1 TRIAL

PubMed Central

Li, Wen; Arasu, Vignesh; Newitt, David C.; Jones, Ella F.; Wilmes, Lisa; Gibbs, Jessica; Kornak, John; Joe, Bonnie N.; Esserman, Laura J.; Hylton, Nola M.

2016-01-01

Functional tumor volume (FTV) measurements by dynamic contrast-enhanced magnetic resonance imaging can predict treatment outcomes for women receiving neoadjuvant chemotherapy for breast cancer. Here, we explore whether the contrast thresholds used to define FTV could be adjusted by breast cancer subtype to improve predictive performance. Absolute FTV and percent change in FTV (ΔFTV) at sequential time-points during treatment were calculated and investigated as predictors of pathologic complete response at surgery. Early percent enhancement threshold (PEt) and signal enhancement ratio threshold (SERt) were varied. The predictive performance of resulting FTV predictors was evaluated using the area under the receiver operating characteristic curve. A total number of 116 patients were studied both as a full cohort and in the following groups defined by hormone receptor (HR) and HER2 receptor subtype: 45 HR+/HER2−, 39 HER2+, and 30 triple negatives. High AUCs were found at different ranges of PEt and SERt levels in different subtypes. Findings from this study suggest that the predictive performance to treatment response by MRI varies by contrast thresholds, and that pathologic complete response prediction may be improved through subtype-specific contrast enhancement thresholds. A validation study is underway with a larger patient population. PMID:28066808

Sequential PET/CT with [18F]-FDG Predicts Pathological Tumor Response to Preoperative Short Course Radiotherapy with Delayed Surgery in Patients with Locally Advanced Rectal Cancer Using Logistic Regression Analysis

PubMed Central

Pecori, Biagio; Lastoria, Secondo; Caracò, Corradina; Celentani, Marco; Tatangelo, Fabiana; Avallone, Antonio; Rega, Daniela; De Palma, Giampaolo; Mormile, Maria; Budillon, Alfredo; Muto, Paolo; Bianco, Francesco; Aloj, Luigi; Petrillo, Antonella; Delrio, Paolo

2017-01-01

Previous studies indicate that FDG PET/CT may predict pathological response in patients undergoing neoadjuvant chemo-radiotherapy for locally advanced rectal cancer (LARC). Aim of the current study is evaluate if pathological response can be similarly predicted in LARC patients after short course radiation therapy alone. Methods: Thirty-three patients with cT2-3, N0-2, M0 rectal adenocarcinoma treated with hypo fractionated short course neoadjuvant RT (5x5 Gy) with delayed surgery (SCRTDS) were prospectively studied. All patients underwent 3 PET/CT studies at baseline, 10 days from RT end (early), and 53 days from RT end (delayed). Maximal standardized uptake value (SUVmax), mean standardized uptake value (SUVmean) and total lesion glycolysis (TLG) of the primary tumor were measured and recorded at each PET/CT study. We use logistic regression analysis to aggregate different measures of metabolic response to predict the pathological response in the course of SCRTDS. Results: We provide straightforward formulas to classify response and estimate the probability of being a major responder (TRG1-2) or a complete responder (TRG1) for each individual. The formulas are based on the level of TLG at the early PET and on the overall proportional reduction of TLG between baseline and delayed PET studies. Conclusions: This study demonstrates that in the course of SCRTDS it is possible to estimate the probabilities of pathological tumor responses on the basis of PET/CT with FDG. Our formulas make it possible to assess the risks associated to LARC borne by a patient in the course of SCRTDS. These risk assessments can be balanced against other health risks associated with further treatments and can therefore be used to make informed therapy adjustments during SCRTDS. PMID:28060889

Sequential PET/CT with [18F]-FDG Predicts Pathological Tumor Response to Preoperative Short Course Radiotherapy with Delayed Surgery in Patients with Locally Advanced Rectal Cancer Using Logistic Regression Analysis.

PubMed

Pecori, Biagio; Lastoria, Secondo; Caracò, Corradina; Celentani, Marco; Tatangelo, Fabiana; Avallone, Antonio; Rega, Daniela; De Palma, Giampaolo; Mormile, Maria; Budillon, Alfredo; Muto, Paolo; Bianco, Francesco; Aloj, Luigi; Petrillo, Antonella; Delrio, Paolo

2017-01-01

Previous studies indicate that FDG PET/CT may predict pathological response in patients undergoing neoadjuvant chemo-radiotherapy for locally advanced rectal cancer (LARC). Aim of the current study is evaluate if pathological response can be similarly predicted in LARC patients after short course radiation therapy alone. Thirty-three patients with cT2-3, N0-2, M0 rectal adenocarcinoma treated with hypo fractionated short course neoadjuvant RT (5x5 Gy) with delayed surgery (SCRTDS) were prospectively studied. All patients underwent 3 PET/CT studies at baseline, 10 days from RT end (early), and 53 days from RT end (delayed). Maximal standardized uptake value (SUVmax), mean standardized uptake value (SUVmean) and total lesion glycolysis (TLG) of the primary tumor were measured and recorded at each PET/CT study. We use logistic regression analysis to aggregate different measures of metabolic response to predict the pathological response in the course of SCRTDS. We provide straightforward formulas to classify response and estimate the probability of being a major responder (TRG1-2) or a complete responder (TRG1) for each individual. The formulas are based on the level of TLG at the early PET and on the overall proportional reduction of TLG between baseline and delayed PET studies. This study demonstrates that in the course of SCRTDS it is possible to estimate the probabilities of pathological tumor responses on the basis of PET/CT with FDG. Our formulas make it possible to assess the risks associated to LARC borne by a patient in the course of SCRTDS. These risk assessments can be balanced against other health risks associated with further treatments and can therefore be used to make informed therapy adjustments during SCRTDS.

Concurrent Chemoradiation with Concomitant Boost in Locally Advanced Rectal Cancer: A Phase II Study.

PubMed

Picardi, Vincenzo; Deodato, Francesco; Guido, Alessandra; Giaccherini, Lucia; Macchia, Gabriella; Gambacorta, Maria A; Arcelli, Alessandra; Farioli, Andrea; Cellini, Francesco; Cuicchi, Dajana; DI Fabio, Francesca; Poggioli, Gilberto; Ardizzoni, Andrea; Frezza, Giovanni; Cilla, Savino; Caravatta, Luciana; Valentini, Vincenzo; Fuccio, Lorenzo; Morganti, Alessio G

2016-08-01

The aim of this study was to evaluate the pathological response of locally advanced rectal cancer after preoperative concurrent two-drug chemotherapy and intensified radiation therapy (RT) with concomitant boost. Patients with T4 tumor or local recurrence were included. A trial based on two-stage Simon's design was planned. RT was performed with 3D-conformal technique. The dose to the mesorectum and pelvic lymph nodes was 45 Gy (1.8 Gy/fraction). A concomitant boost was delivered to Gross Tumor Volume (GTV) 2 cm margin to a total dose of 55 Gy (2.2 Gy/fraction). The following concurrent chemotherapy was administered: Raltitrexed (3 mg/m(2)) and oxaliplatin (130 mg/m(2)) on days 1, 17, and 35 of RT. Pathological response was evaluated according to the Mandard classification. Toxicities were scored according to the Common Terminology Criteria for Adverse Events v3.0 scale. Eighteen patients (median age=64.5 years) were enrolled. The median follow-up was 22 months (range=2-36 months). After chemoradiation treatment, 16 patients underwent surgical resection (seven anterior resections and nine abdominal-perineal amputation); two patients did not undergo surgery due to early metastatic progression or refusal. R0 resection was achieved in all patients who underwent surgery. Five patients had pathological complete response [27.7%; 95% confidence interval (CI)=9.7-53.5%] and two patients showed only microscopic residual disease (11.1%; 95% CI=0.1-34.7%). Mandard grades 1 and 2 were detected in seven patients (38.9%; 95% CI=17.3-64.3%). Acute grade 3 or more toxicity was found in eight patients (44.4%; 95% CI=21.5-69.2%): one leucopenia-neutropenia, one liver, one skin and five cases of gastrointestinal toxicities. No patient had local tumor recurrence. One-, 2- and 3-year cumulative disease-free survival were 93.8%. One-, 2- and 3-year cumulative overall survival were 92.3%. Concurrent chemoradiation with concomitant boost in patients with advanced rectal cancer allows complete or near-complete pathological response in more than 38% of patients. However, severe acute toxicity was reported in more than one-third of patients. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Neoadjuvant Long-Course Chemoradiotherapy for Rectal Cancer: Does Time to Surgery Matter?

PubMed Central

Panagiotopoulou, Ioanna G.; Parashar, Deepak; Qasem, Eyas; Mezher-Sikafi, Rasha; Parmar, Jitesh; Wells, Alan D.; Bajwa, Farrukh M.; Menon, Madhav; Jephcott, Catherine R.

2015-01-01

The objective of this paper was to evaluate whether delaying surgery following long-course chemoradiotherapy for rectal cancer correlates with pathologic complete response. Pre-operative chemoradiotherapy (CRT) is standard practice in the UK for the management of locally advanced rectal cancer. Optimal timing of surgery following CRT is still not clearly defined. All patients with a diagnosis of rectal cancer who had undergone long-course CRT prior to surgery between January 2008 and December 2011 were included. Statistical analysis was performed using Stata 11. Fifty-nine patients received long-course CRT prior to surgery in the selected period. Twenty-seven percent (16/59) of patients showed a complete histopathologic response and 59.3% (35/59) of patients had tumor down-staging from radiologically-assessed node positive to histologically-proven node negative disease. There was no statistically significant delay to surgery after completion of CRT in the 16 patients with complete response (CR) compared with the rest of the group [IR: incomplete response; CR group median: 74.5 days (IQR: 70–87.5) and IR group median: 72 days (IQR: 57–83), P = 0.470]. Although no statistically significant predictors of either complete response or tumor nodal status down-staging were identified in logistic regression analyses, a trend toward complete response was seen with longer delay to surgery following completion of long-course CRT. PMID:26414816

Radiochemotherapy in Anal Cancer: cCR, clinical outcomes and quality of life using two different treatment schedules

PubMed Central

Di Santo, Sara; Trignani, Marianna; Neri, Matteo; Milano, Angelo; Innocenti, Paolo; Taraborrelli, Maria; Augurio, Antonietta; Vinciguerra, Annamaria; Di Tommaso, Monica; Ursini, Lucia Anna; Di Pilla, Angelo; Di Nicola, Marta; Genovesi, Domenico

2014-01-01

Aim Main endpoint was a response rate to therapy; secondary endpoints were disease-free survival, overall survival, acute and late toxicities, specially in terms of anorectal and urinary continence. Background Radiochemotherapy for anal cancer achieves a good clinical response, locoregional control, anal function preservation. However, oncologic outcomes can differ using radiotherapy plus fluorouracil and mytomicin vs. cisplatin and fluorouracil. Methods Between 2000 and 2012, 27 anal cancer patients receiving radiotherapy combined with two different radiochemotherapy schedules, fluorouracil and mytomicin (group A) and cisplatin plus fluorouracil (group B). The Kaplan–Meier method was also used to estimate local control, overall survival and disease free survival. Statistical significance between curves was evaluated using the Log-rank test. Results Complete pathological response was found in 85.2% of patients, with higher rates of response in the group A (100% vs. 63.6%, p = 0.039). No significantly difference was found between the two groups for the other endpoints. Low rates of both acute and late toxicities were recorded. Conclusion Radiotherapy plus fluorouracil and mytomicin provide a better complete pathological response than radiotherapy plus cisplatin and fluorouracil and a greater rate of anal sphincter function preservation. Globally, radiochemotherapy of the anal cancer provides excellent clinical outcomes with a good profile of acute and late toxicity, without difference between the two groups studied. PMID:25859401

Neoadjuvant Treatment With Single-Agent Cetuximab Followed by 5-FU, Cetuximab, and Pelvic Radiotherapy: A Phase II Study in Locally Advanced Rectal Cancer

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

Bertolini, Federica; Chiara, Silvana; Bengala, Carmelo

2009-02-01

Purpose: Preoperative chemoradiotherapy followed by surgery represents the standard of care for locally advanced rectal cancer (LARC). Cetuximab has proved activity in advanced colorectal cancer, and its incorporation in preoperative treatment may increase tumor downstaging. Methods and Materials: After biopsy and staging, uT3/uT4 N0/+ LARC received single-agent cetuximab in three doses, followed by weekly cetuximab plus 5-fluorouracil (5-FU), concomitantly with RT. Sample size was calculated according to Bryant and Day test, a two-stage design with at least 10 pathologic complete remissions observed in 60 patients (pts) able to complete the treatment plan. Results: Forty pts with LARC were entered: male/femalemore » = 34/6; median age: 61 (range, 28-77); 12 uT3N0 Ed(30%); 25 uT3N1 (62%); 3 uT4N1 (8%); all Eastern Cooperative Oncology Group = 0. Thirty-five pts completed neoadjuvant treatment; 5 (12%) withdrew therapy after one cetuximab administration: three for hypersensitivity reactions, one for rapid progression, and one for purulent arthritis. They continued 5-FU in continuous infusion in association with RT. Thirty-one pts (77%) presented with acnelike rash; dose reduction/interruption of treatment was necessary in six pts (15%): two for Grade 3 acnelike rash, two for Grade 3 gastrointestinal toxicity, and two for refusal. Thirty-eight pts were evaluable for pathological response (one patient refused surgery, and one was progressed during neoadjuvant treatment). Pathological staging was: pT0N0 three pts (8%), pT1N0 1 pt (3%); pT2N0 13 pts (34%), and pT3 19 pts (50%) (N0:9, N1:5; N2:5); pT4 2 pts (5%). Conclusions: Preoperative treatment with 5-FU, cetuximab, and pelvic RT is feasible with acceptable toxicities; however, the rate of pathologic responses is disappointingly low.« less

Preoperative Intensity Modulated Radiation Therapy and Chemotherapy for Locally Advanced Vulvar Carcinoma: Analysis of Pattern of Relapse

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

Beriwal, Sushil, E-mail: beriwals@upmc.edu; Shukla, Gaurav; Shinde, Ashwin

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; 13more » 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.« less

The p53 breast cancer tissue biomarker in Indian women

PubMed Central

Patil, Vinayak W; Tayade, Mukund B; Pingale, Sangeeta A; Dalvi, Shubhangi M; Rajekar, Rajesh B; Deshmukh, Hemkant M; Patil, Shital D; Singhai, Rajeev

2011-01-01

Background Combination chemotherapy is highly effective in locally advanced breast cancer. A negative expression of biomarker p53 indicates a higher chance of responding to this regimen. Patients’ p53 status may be used as a biological cancer marker to identify those who would benefit from more aggressive treatments. Aims The role of p53 in modulating apoptosis has suggested that it may affect the efficacy of anticancer agents. p53 alterations in 80 patients with locally advanced breast cancer IIIB undergoing neoadjuvant chemotherapy were prospectively evaluated. Materials and methods Patients received three cycles of paclitaxel (175 mg/m2) and doxorubicin (60 mg/m2) every 21 days. Tumor sections were analyzed before treatment for altered patterns of p53 expression, using immunohistochemistry and DNA sequencing. Results An overall response rate of 83.5% was obtained, including 15.1% complete pathological responses. The regimen was well tolerated with 17.7% grade 2/3 nausea and 12.8% grade 3/4 leukopenia. There was a statistically significant correlation between response and expression of p53. Of 25 patients who obtained a complete clinical response, only two were classified as p53-positive (P = 0.004, χ2). Of 11 patients who obtained a complete pathological remission, one was positive (P = 0.099, χ2). Conclusion Immunohistochemical (IHC) analysis has been shown to be a prognostic factor for patients with breast cancer in India. Paclitaxel is one of the most promising anticancer agents for the therapy of breast cancer, where it has also shown activity in tumors resistant to doxorubicin. PMID:24367177

FPA-FTIR Microspectroscopy for Monitoring Chemotherapy Efficacy in Triple-Negative Breast Cancer

NASA Astrophysics Data System (ADS)

Zawlik, Izabela; Kaznowska, Ewa; Cebulski, Jozef; Kolodziej, Magdalena; Depciuch, Joanna; Vongsvivut, Jitraporn; Cholewa, Marian

2016-11-01

Triple-negative breast cancer is the most aggressive breast cancer subtype with limited treatment options and a poor prognosis. Approximately 70% of triple-negative breast cancer patients fail to achieve a pathologic complete response (pCR) after chemotherapy due to the lack of targeted therapies for this subtype. We report here the development of a focal-plane-array Fourier transform infrared (FPA-FTIR) microspectroscopic technique combined with principal component analysis (PCA) for monitoring chemotherapy effects in triple-negative breast cancer patients. The PCA results obtained using the FPA-FTIR spectral data collected from the same patients before and after the chemotherapy revealed discriminatory features that were consistent with the pathologic and clinical responses to chemotherapy, indicating the potential of the technique as a monitoring tool for observing chemotherapy efficacy.

Sex Disparities After Induction Chemoradiotherapy and Esophagogastrectomy for Esophageal Cancer.

PubMed

Rowse, Phillip G; Jaroszewski, Dawn E; Thomas, Mathew; Harold, Kristi; Harmsen, William S; Shen, K Robert

2017-10-01

The impact of sex on the outcomes of treatment for locally advanced esophageal carcinoma is unclear. This study analyzed the impact of sex on response to neoadjuvant chemoradiotherapy (nCRT), tumor recurrence, and survival. From January 1990 through December 2013, female patients who received nCRT followed by esophagogastrectomy at 3 affiliated centers were compared with control male patients based on age, pretreatment clinical stage, histologic type, and surgical era. Only patients staged preoperatively with computed tomographic scans and endoscopic ultrasonography (EUS) were included. There were 366 patients (145 women and 221 men). The median female age was 64 years (range, 22-81 years), whereas male patients were 61 years (range, 33-82 years). The histologic type was adenocarcinoma in 105 (72%) women and 192 (87%) men, and it was squamous cell carcinoma in 40 (28%) women and 29 (13%) men (p = 0.005). Women were more likely to attain either a complete pathologic (CP) response or a nearly complete pathologic (NCP) response to induction therapy (84 [58%]) compared with men (103 [47%]; p = 0.034). Men had an 80% increased risk of recurrence (hazard ratio [HR], 1.80; 95% CI, 1.15-2.68; p = 0.008). There was no sex association with risk of death (p = 0.538). Irrespective of sex, a partial responder (relative to a complete or nearly complete responder) was 3 times more likely to have recurrence (HR, 2.96; 95% CI, 1.98-4.43; p < 0.001) and 2.5 times more likely to die (HR, 2.56; 95% CI, 1.88-3.48; p < 0.001). Female sex correlated with improved rates of achieving either a CP response or an NCP response after neoadjuvant chemotherapy and a smaller likelihood of experiencing tumor recurrence. Future efforts should be directed at understanding determinants of this sex disparity. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Ubiquitinated Sirtuin 1 (SIRT1) Function Is Modulated during DNA Damage-induced Cell Death and Survival*

PubMed Central

Peng, Lirong; Yuan, Zhigang; Li, Yixuan; Ling, Hongbo; Izumi, Victoria; Fang, Bin; Fukasawa, Kenji; Koomen, John; Chen, Jiandong; Seto, Edward

2015-01-01

Downstream signaling of physiological and pathological cell responses depends on post-translational modification such as ubiquitination. The mechanisms regulating downstream DNA damage response (DDR) signaling are not completely elucidated. Sirtuin 1 (SIRT1), the founding member of Class III histone deacetylases, regulates multiple steps in DDR and is closely associated with many physiological and pathological processes. However, the role of post-translational modification or ubiquitination of SIRT1 during DDR is unclear. We show that SIRT1 is dynamically and distinctly ubiquitinated in response to DNA damage. SIRT1 was ubiquitinated by the MDM2 E3 ligase in vitro and in vivo. SIRT1 ubiquitination under normal conditions had no effect on its enzymatic activity or rate of degradation; hypo-ubiquitination, however, reduced SIRT1 nuclear localization. Ubiquitination of SIRT1 affected its function in cell death and survival in response to DNA damage. Our results suggest that ubiquitination is required for SIRT1 function during DDR. PMID:25670865

A phase II study of preoperative chemoradiation with tegafur-uracil plus leucovorin for locally advanced rectal cancer with pharmacogenetic analysis.

PubMed

Kim, Sun Young; Baek, Ji Yeon; Oh, Jae Hwan; Park, Sung Chan; Sohn, Dae Kyung; Kim, Min Ju; Chang, Hee Jin; Kong, Sun-Young; Kim, Dae Yong

2017-03-27

This study aimed to evaluate the efficacy of a high dose of oral tegafur-uracil (400 mg/m 2 ) plus leucovorin with preoperative chemoradiation of locally advanced rectal cancer and to explore the impact of polymorphisms of cytochrome P 2A6 (CYP2A6), uridine monophosphate synthetase (UMPS), and ATP-binding cassette B1 (ABCB1) on clinical outcome. Patients with cT3 or cT4 rectal cancer were enrolled and were given tegafur-uracil 400 mg/m 2 /day and leucovorin 90 mg/m 2 /day for 7 days a week during preoperative chemoradiation (50.4 Gy/28 fractions) in this phase II trial. Primary endpoint was pathologic complete response rate, and the secondary endpoint was to explore the association between clinical outcomes and genetic polymorphisms CYP2A6 (*4, *7, *9 and *10), UMPS G638C, and three ABCB1 genotypes (C1236T, C3435T, and G2677T). Ninety-one patients were given study treatment, and 90 underwent surgery. Pathologic complete response was noted in 10 patients (11.1%). There was no grade 4 or 5 toxicity; 20 (22.0%) experienced grade 3 toxicities, including diarrhea (10, 11.0%), abdominal pain (2, 2.2%), and anemia (2, 2.2%). Relapse-free survival and overall survival at 5 years were 88.6% and 94.2%, respectively. Patients with the UMPS 638 CC genotype experienced significantly more frequent grade 2 or 3 diarrhea (p for trend = 0.018). Preoperative chemoradiation with tegafur-uracil 400 mg/m 2 /day with leucovorin was feasible, but did not meet the expected pathologic complete response rate. The UMPS 638 CC genotype might be a candidate biomarker predicting toxicity in patients receiving tegafur-uracil/leucovorin-based preoperative chemoradiation for locally advanced rectal cancer. ISRCTN11812525 , registered on 25 July 2016. Retrospectively registered.

Recommendations for standardized pathological characterization of residual disease for neoadjuvant clinical trials of breast cancer by the BIG-NABCG collaboration

PubMed Central

Bossuyt, V.; Provenzano, E.; Symmans, W. F.; Boughey, J. C.; Coles, C.; Curigliano, G.; Dixon, J. M.; Esserman, L. J.; Fastner, G.; Kuehn, T.; Peintinger, F.; von Minckwitz, G.; White, J.; Yang, W.; Badve, S.; Denkert, C.; MacGrogan, G.; Penault-Llorca, F.; Viale, G.; Cameron, D.; Earl, Helena; Alba, Emilio; Lluch, Ana; Albanell, Joan; Amos, Keith; Biernat, Wojciech; Bonnefoi, Hervé; Buzdar, Aman; Cane, Paul; Pinder, Sarah; Carson, Lesley; Dickson-Witmer, Diana; Gong, Gyungyub; Green, Jimmy; Hsu, Chih-Yi; Tseng, Ling-Ming; Kroep, Judith; Leitch, A. Marilyn; Sarode, Venetia; Mamounas, Eleftherios; Marcom, Paul Kelly; Nuciforo, Paolo; Paik, Soonmyung; Peg, Vicente; Peston, David; Pierga, Jean-Yves; Quintela-Fandino, Miguel; Salgado, Roberto; Sikov, William; Thomas, Jeremy; Unzeitig, Gary; Wesseling, Jelle

2015-01-01

Neoadjuvant systemic therapy (NAST) provides the unique opportunity to assess response to treatment after months rather than years of follow-up. However, significant variability exists in methods of pathologic assessment of response to NAST, and thus its interpretation for subsequent clinical decisions. Our international multidisciplinary working group was convened by the Breast International Group-North American Breast Cancer Group (BIG-NABCG) collaboration and tasked to recommend practical methods for standardized evaluation of the post-NAST surgical breast cancer specimen for clinical trials that promote accurate and reliable designation of pathologic complete response (pCR) and meaningful characterization of residual disease. Recommendations include multidisciplinary communication; clinical marking of the tumor site (clips); and radiologic, photographic, or pictorial imaging of the sliced specimen, to map the tissue sections and reconcile macroscopic and microscopic findings. The information required to define pCR (ypT0/is ypN0 or ypT0 yp N0), residual ypT and ypN stage using the current AJCC/UICC system, and the Residual Cancer Burden system were recommended for quantification of residual disease in clinical trials. PMID:26019189

(11)C-Choline PET/CT as a guide to radiation treatment planning of lymph-node relapses in prostate cancer patients.

PubMed

Picchio, M; Berardi, G; Fodor, A; Busnardo, E; Crivellaro, C; Giovacchini, G; Fiorino, C; Kirienko, M; Incerti, E; Messa, C; Gianolli, L; Di Muzio, N

2014-07-01

To evaluate, in prostate cancer (PCa) patients the potential of (11)C-choline PET/CT as a guide to helical tomotherapy (HTT) of lymph-node (LN) relapses with simultaneous integrated boost (SIB). The efficacy and feasibility of HTT in terms of acute toxicity were assessed. We enrolled 83 PCa patients (mean age 68 years, range 51 - 82 years) with biochemical recurrence after radical primary treatment (mean serum PSA 7.61 ng/ml, range 0.37 - 187.00 ng/ml; PSA0) who showed pathological findings on (11)C-choline PET/CT only at the LN site. (11)C-Choline PET/CT was performed for restaging and then for radiation treatment planning (PET/CT0). Of the 83 patients, 8 experienced further LN relapse, of whom 5 were retreated once and 3 were retreated twice (total 94 radiotherapy treatments). All pelvic and/or abdominal LNs positive on PET/CT0 were treated with high doses using SIB. Doses were in the range 36 - 74 Gy administered in 28 fractions. After the end of HTT (mean 83 days, range 16 - 365 days), serum PSA was measured in all patients (PSA1) and compared with PSA0 to evaluate early biochemical response. In 47 patients PET/CT was repeated (PET/CT1) to assess metabolic responses at the treated areas. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) were used to assess acute toxicity. PET/CT0 revealed pathological LNs in the pelvis in 49 patients, pathological LNs in the abdomen in 15 patients pathological LNs in both the pelvis and abdomen in 18 patients, and pathological LNs in the pelvis or abdomen and other sites in 12 patients. All these sites were treated with HTT. With respect to PSA0, PSA1 (mean 6.28 ng/ml, range 0.00 - 220.46 ng/ml) showed a complete biochemical response after 66 of the 94 HTT treatments, a partial response after 12 treatments, stable disease after 1 treatment and progression of disease after 15 treatments. Of the 47 patients receiving PET/CT1, 20 showed a complete metabolic response at the treated area, 22 a partial metabolic response, 3 progression of disease and 2 stable disease. HTT with SIB was well tolerated in all patients. Grade 3 acute toxicity in the genitourinary tract was observed in two patients. (11)C-Choline PET/CT is a valuable tool for planning and monitoring HTT in LN relapse after primary treatment. High-dose hypofractionated (11)C-choline PET/CT-guided HTT with SIB is well tolerated and is associated with a high early biochemical response rate.

[A Case of Liver Metastasis from Esophageal Cancer Successfully Treated by Surgical Resection after Chemotherapy with Weekly-Paclitaxel].

PubMed

Nozawa, Akinori; Kubo, Naoshi; Shimizu, Sadatoshi; Murata, Akihiro; Kanazawa, Akishige; Kodai, Shintaro; Urata, Yorihisa; Miura, Kotaro; Tauchi, Jun; Sakurai, Katsunori; Tachimori, Akiko; Tamamori, Yutaka; Inoue, Toru; Yamashita, Yoshito; Nishiguchi, Yukio

2017-11-01

A 58-year-old man complaining of dysphagia was admitted to our hospital and diagnosed with esophageal cancer.He underwent thoracoscopic subtotal esophagectomy with 3-field lymph node dissection and reconstruction with a gastric tube created by hand-assisted laparoscopy.The pathological diagnosis was classified as AeLtG, pT3N2M0, pStage III .He was subsequently treated with systemic chemotherapy with 5-fluorouracil and cisplatin.After 2 courses, a single liver metastatic tumor appeared at segment 5.As chemotherapy against the recurrence, weekly-paclitaxel was administered.After 2 courses, the metastatic liver tumor reduced in size.Subsequently, laparoscopic partial liver resection was performed 11 months after first surgery.The pathological finding was negative for malignancy(pathological complete response).

Role of genetic polymorphisms in NFKB-mediated inflammatory pathways in response to primary chemoradiation therapy for rectal cancer.

PubMed

Dzhugashvili, Maia; Luengo-Gil, Ginés; García, Teresa; González-Conejero, Rocío; Conesa-Zamora, Pablo; Escolar, Pedro Pablo; Calvo, Felipe; Vicente, Vicente; Ayala de la Peña, Francisco

2014-11-01

To investigate whether polymorphisms of genes related to inflammation are associated with pathologic response (primary endpoint) in patients with rectal cancer treated with primary chemoradiation therapy (PCRT). Genomic DNA of 159 patients with locally advanced rectal cancer treated with PCRT was genotyped for polymorphisms rs28362491 (NFKB1), rs1213266/rs5789 (PTGS1), rs5275 (PTGS2), and rs16944/rs1143627 (IL1B) using TaqMan single nucleotide polymorphism genotyping assays. The association between each genotype and pathologic response (poor response vs complete or partial response) was analyzed using logistic regression models. The NFKB1 DEL/DEL genotype was associated with pathologic response (odds ratio [OR], 6.39; 95% confidence interval [CI], 0.78-52.65; P=.03) after PCRT. No statistically significant associations between other polymorphisms and response to PCRT were observed. Patients with the NFKB1 DEL/DEL genotype showed a trend for longer disease-free survival (log-rank test, P=.096) and overall survival (P=.049), which was not significant in a multivariate analysis that included pathologic response. Analysis for 6 polymorphisms showed that patients carrying the haplotype rs28362491-DEL/rs1143627-A/rs1213266-G/rs5789-C/rs5275-A/rs16944-G (13.7% of cases) had a higher response rate to PCRT (OR, 8.86; 95% CI, 1.21-64.98; P=.034) than the reference group (rs28362491-INS/rs1143627-A/rs1213266-G/rs5789-C/rs5275-A/rs16944-G). Clinically significant (grade ≥2) acute organ toxicity was also more frequent in patients with that same haplotype (OR, 4.12; 95% CI, 1.11-15.36; P=.037). Our results suggest that genetic variation in NFKB-related inflammatory pathways might influence sensitivity to primary chemoradiation for rectal cancer. If confirmed, an inflammation-related radiogenetic profile might be used to select patients with rectal cancer for preoperative combined-modality treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

Effect of increasing radiation dose on pathologic complete response in rectal cancer patients treated with neoadjuvant chemoradiation therapy.

PubMed

Hall, Matthew D; Schultheiss, Timothy E; Smith, David D; Fakih, Marwan G; Wong, Jeffrey Y C; Chen, Yi-Jen

2016-12-01

Neoadjuvant chemoradiation therapy (CRT) increases pathological complete response (pCR) rates compared to radiotherapy alone in patients with stage II-III rectal cancer. Limited evidence addresses whether radiotherapy dose escalation further improves pCR rates. Our purpose is to measure the effects of radiotherapy dose and other factors on post-therapy pathologic tumor (ypT) and nodal stage in rectal cancer patients treated with neoadjuvant CRT followed by mesorectal excision. A non-randomized comparative effectiveness analysis was performed of rectal cancer patients treated in 2000-2013 from the National Oncology Data Alliance™ (NODA), a pooled database of cancer registries from >150 US hospitals. The NODA contains the same data submitted to state cancer registries and SEER combined with validated radiotherapy and chemotherapy records. Eligible patients were treated with neoadjuvant CRT followed by proctectomy and had complete data on treatment start dates, radiotherapy dose, clinical tumor (cT) and ypT stage, and number of positive nodes at surgery (n = 3298 patients). Multivariable logistic regression was used to assess the predictive value of independent variables on achieving a pCR. On multivariable regression, radiotherapy dose, cT stage, and time interval between CRT and surgery were significant predictors of achieving a pCR. After adjusting for the effect of other variates, patients treated with higher radiotherapy doses were also more likely to have negative nodes at surgery and be downstaged from cT3-T4 and/or node positive disease to ypT0-T2N0 after neoadjuvant CRT. Our study suggests that increasing dose significantly improved pCR rates and downstaging in rectal cancer patients treated with neoadjuvant CRT followed by surgery.

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

Chen, Pei-Chun; Chen, Yen-Ching; Research Center for Gene, Environment, and Human Health, College of Public Health, National Taiwan University, Taiwan

Purpose: To identify germline polymorphisms to predict concurrent chemoradiation therapy (CCRT) response in esophageal cancer patients. Materials and Methods: A total of 139 esophageal cancer patients treated with CCRT (cisplatin-based chemotherapy combined with 40 Gy of irradiation) and subsequent esophagectomy were recruited at the National Taiwan University Hospital between 1997 and 2008. After excluding confounding factors (i.e., females and patients aged {>=}70 years), 116 patients were enrolled to identify single nucleotide polymorphisms (SNPs) associated with specific CCRT responses. Genotyping arrays and mass spectrometry were used sequentially to determine germline polymorphisms from blood samples. These polymorphisms remain stable throughout disease progression,more » unlike somatic mutations from tumor tissues. Two-stage design and additive genetic models were adopted in this study. Results: From the 26 SNPs identified in the first stage, 2 SNPs were found to be significantly associated with CCRT response in the second stage. Single nucleotide polymorphism rs16863886, located between SGPP2 and FARSB on chromosome 2q36.1, was significantly associated with a 3.93-fold increase in pathologic complete response to CCRT (95% confidence interval 1.62-10.30) under additive models. Single nucleotide polymorphism rs4954256, located in ZRANB3 on chromosome 2q21.3, was associated with a 3.93-fold increase in pathologic complete response to CCRT (95% confidence interval 1.57-10.87). The predictive accuracy for CCRT response was 71.59% with these two SNPs combined. Conclusions: This is the first study to identify germline polymorphisms with a high accuracy for predicting CCRT response in the treatment of esophageal cancer.« less

The effectiveness of annotated (vs. non-annotated) digital pathology slides as a teaching tool during dermatology and pathology residencies.

PubMed

Marsch, Amanda F; Espiritu, Baltazar; Groth, John; Hutchens, Kelli A

2014-06-01

With today's technology, paraffin-embedded, hematoxylin & eosin-stained pathology slides can be scanned to generate high quality virtual slides. Using proprietary software, digital images can also be annotated with arrows, circles and boxes to highlight certain diagnostic features. Previous studies assessing digital microscopy as a teaching tool did not involve the annotation of digital images. The objective of this study was to compare the effectiveness of annotated digital pathology slides versus non-annotated digital pathology slides as a teaching tool during dermatology and pathology residencies. A study group composed of 31 dermatology and pathology residents was asked to complete an online pre-quiz consisting of 20 multiple choice style questions, each associated with a static digital pathology image. After completion, participants were given access to an online tutorial composed of digitally annotated pathology slides and subsequently asked to complete a post-quiz. A control group of 12 residents completed a non-annotated version of the tutorial. Nearly all participants in the study group improved their quiz score, with an average improvement of 17%, versus only 3% (P = 0.005) in the control group. These results support the notion that annotated digital pathology slides are superior to non-annotated slides for the purpose of resident education. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Use of Cox's Cure Model to Establish Clinical Determinants of Long-Term Disease-Free Survival in Neoadjuvant-Chemotherapy-Treated Breast Cancer Patients without Pathologic Complete Response.

PubMed

Asano, Junichi; Hirakawa, Akihiro; Hamada, Chikuma; Yonemori, Kan; Hirata, Taizo; Shimizu, Chikako; Tamura, Kenji; Fujiwara, Yasuhiro

2013-01-01

In prognostic studies for breast cancer patients treated with neoadjuvant chemotherapy (NAC), the ordinary Cox proportional-hazards (PH) model has been often used to identify prognostic factors for disease-free survival (DFS). This model assumes that all patients eventually experience relapse or death. However, a subset of NAC-treated breast cancer patients never experience these events during long-term follow-up (>10 years) and may be considered clinically "cured." Clinical factors associated with cure have not been studied adequately. Because the ordinary Cox PH model cannot be used to identify such clinical factors, we used the Cox PH cure model, a recently developed statistical method. This model includes both a logistic regression component for the cure rate and a Cox regression component for the hazard for uncured patients. The purpose of this study was to identify the clinical factors associated with cure and the variables associated with the time to recurrence or death in NAC-treated breast cancer patients without a pathologic complete response, by using the Cox PH cure model. We found that hormone receptor status, clinical response, human epidermal growth factor receptor 2 status, histological grade, and the number of lymph node metastases were associated with cure.

Computational pathology of pre-treatment biopsies identifies lymphocyte density as a predictor of response to neoadjuvant chemotherapy in breast cancer.

PubMed

Ali, H Raza; Dariush, Aliakbar; Provenzano, Elena; Bardwell, Helen; Abraham, Jean E; Iddawela, Mahesh; Vallier, Anne-Laure; Hiller, Louise; Dunn, Janet A; Bowden, Sarah J; Hickish, Tamas; McAdam, Karen; Houston, Stephen; Irwin, Mike J; Pharoah, Paul D P; Brenton, James D; Walton, Nicholas A; Earl, Helena M; Caldas, Carlos

2016-02-16

There is a need to improve prediction of response to chemotherapy in breast cancer in order to improve clinical management and this may be achieved by harnessing computational metrics of tissue pathology. We investigated the association between quantitative image metrics derived from computational analysis of digital pathology slides and response to chemotherapy in women with breast cancer who received neoadjuvant chemotherapy. We digitised tissue sections of both diagnostic and surgical samples of breast tumours from 768 patients enrolled in the Neo-tAnGo randomized controlled trial. We subjected digital images to systematic analysis optimised for detection of single cells. Machine-learning methods were used to classify cells as cancer, stromal or lymphocyte and we computed estimates of absolute numbers, relative fractions and cell densities using these data. Pathological complete response (pCR), a histological indicator of chemotherapy response, was the primary endpoint. Fifteen image metrics were tested for their association with pCR using univariate and multivariate logistic regression. Median lymphocyte density proved most strongly associated with pCR on univariate analysis (OR 4.46, 95 % CI 2.34-8.50, p < 0.0001; observations = 614) and on multivariate analysis (OR 2.42, 95 % CI 1.08-5.40, p = 0.03; observations = 406) after adjustment for clinical factors. Further exploratory analyses revealed that in approximately one quarter of cases there was an increase in lymphocyte density in the tumour removed at surgery compared to diagnostic biopsies. A reduction in lymphocyte density at surgery was strongly associated with pCR (OR 0.28, 95 % CI 0.17-0.47, p < 0.0001; observations = 553). A data-driven analysis of computational pathology reveals lymphocyte density as an independent predictor of pCR. Paradoxically an increase in lymphocyte density, following exposure to chemotherapy, is associated with a lack of pCR. Computational pathology can provide objective, quantitative and reproducible tissue metrics and represents a viable means of outcome prediction in breast cancer. ClinicalTrials.gov NCT00070278 ; 03/10/2003.

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

Dzhugashvili, Maia; Department of Radiation Oncology, Madrid Oncology Institute; Luengo-Gil, Ginés

Purpose: To investigate whether polymorphisms of genes related to inflammation are associated with pathologic response (primary endpoint) in patients with rectal cancer treated with primary chemoradiation therapy (PCRT). Methods and Materials: Genomic DNA of 159 patients with locally advanced rectal cancer treated with PCRT was genotyped for polymorphisms rs28362491 (NFKB1), rs1213266/rs5789 (PTGS1), rs5275 (PTGS2), and rs16944/rs1143627 (IL1B) using TaqMan single nucleotide polymorphism genotyping assays. The association between each genotype and pathologic response (poor response vs complete or partial response) was analyzed using logistic regression models. Results: The NFKB1 DEL/DEL genotype was associated with pathologic response (odds ratio [OR], 6.39; 95%more » confidence interval [CI], 0.78-52.65; P=.03) after PCRT. No statistically significant associations between other polymorphisms and response to PCRT were observed. Patients with the NFKB1 DEL/DEL genotype showed a trend for longer disease-free survival (log-rank test, P=.096) and overall survival (P=.049), which was not significant in a multivariate analysis that included pathologic response. Analysis for 6 polymorphisms showed that patients carrying the haplotype rs28362491-DEL/rs1143627-A/rs1213266-G/rs5789-C/rs5275-A/rs16944-G (13.7% of cases) had a higher response rate to PCRT (OR, 8.86; 95% CI, 1.21-64.98; P=.034) than the reference group (rs28362491-INS/rs1143627-A/rs1213266-G/rs5789-C/rs5275-A/rs16944-G). Clinically significant (grade ≥2) acute organ toxicity was also more frequent in patients with that same haplotype (OR, 4.12; 95% CI, 1.11-15.36; P=.037). Conclusions: Our results suggest that genetic variation in NFKB-related inflammatory pathways might influence sensitivity to primary chemoradiation for rectal cancer. If confirmed, an inflammation-related radiogenetic profile might be used to select patients with rectal cancer for preoperative combined-modality treatment.« less

Specific pathologist responses for Standard for Exchange of Nonclinical Data (SEND).

PubMed

Watanabe, Atsushi; Kusuoka, Osamu; Sato, Norihiro; Nakazono, Osamu; Wasko, Michael; Potenta, Daniel; Nakae, Dai; Hatakeyama, Hirofumi; Iwata, Hijiri; Naota, Misaki; Anzai, Takayuki

2017-07-01

The Standard for Exchange of Nonclinical Data (SEND), introduced by the US Food and Drug Administration (FDA), is a scheme for the computerization, electronic application, and screening of preclinical data. Since its establishment, related organizations have been working together to implement SEND. However, it is difficult for individual pharmaceutical companies that often outsource to achieve complete compliance with SEND; hence, the cooperation of contract research organizations (CROs) and SEND Registered Solution Providers (RSPs) is indispensable. In SEND, most data, including those on pathology findings, are converted into controlled terminology (CT), but it is not a simple process to convert findings or levels of severity in the field of pathology, which is a descriptive science. The authors have successfully completed an FDA trial submission for a toxicology test conducted at a CRO and in doing so acquired important knowledge. This article presents a clear picture of such important knowledge from a pathologist's viewpoint.

Specific pathologist responses for Standard for Exchange of Nonclinical Data (SEND)

PubMed Central

Watanabe, Atsushi; Kusuoka, Osamu; Sato, Norihiro; Nakazono, Osamu; Wasko, Michael; Potenta, Daniel; Nakae, Dai; Hatakeyama, Hirofumi; Iwata, Hijiri; Naota, Misaki; Anzai, Takayuki

2017-01-01

The Standard for Exchange of Nonclinical Data (SEND), introduced by the US Food and Drug Administration (FDA), is a scheme for the computerization, electronic application, and screening of preclinical data. Since its establishment, related organizations have been working together to implement SEND. However, it is difficult for individual pharmaceutical companies that often outsource to achieve complete compliance with SEND; hence, the cooperation of contract research organizations (CROs) and SEND Registered Solution Providers (RSPs) is indispensable. In SEND, most data, including those on pathology findings, are converted into controlled terminology (CT), but it is not a simple process to convert findings or levels of severity in the field of pathology, which is a descriptive science. The authors have successfully completed an FDA trial submission for a toxicology test conducted at a CRO and in doing so acquired important knowledge. This article presents a clear picture of such important knowledge from a pathologist’s viewpoint. PMID:28798527

Addition of zoledronic acid to neoadjuvant chemotherapy does not enhance tumor response in patients with HER2-negative stage II/III breast cancer: the NEOZOTAC trial (BOOG 2010-01).

PubMed

Charehbili, A; van de Ven, S; Smit, V T H B M; Meershoek-Klein Kranenbarg, E; Hamdy, N A T; Putter, H; Heijns, J B; van Warmerdam, L J C; Kessels, L; Dercksen, M; Pepels, M J; Maartense, E; van Laarhoven, H W M; Vriens, B; Wasser, M N; van Leeuwen-Stok, A E; Liefers, G J; van de Velde, C J H; Nortier, J W R; Kroep, J R

2014-05-01

The role of zoledronic acid (ZA) when added to the neoadjuvant treatment of breast cancer (BC) in enhancing the clinical and pathological response of tumors is unclear. The effect of ZA on the antitumor effect of neoadjuvant chemotherapy has not prospectively been studied before. NEOZOTAC is a national, multicenter, randomized study comparing the efficacy of TAC (docetaxel, adriamycin and cyclophosphamide i.v.) followed by granulocyte colony-stimulating factor on day 2 with or without ZA 4 mg i.v. q 3 weeks inpatients withstage II/III, HER2-negative BC. We present data on the pathological complete response (pCR in breast and axilla), on clinical response using MRI, and toxicity. Post hoc subgroup analyses were undertaken to address the predictive value of menopausal status. Addition of ZA to chemotherapy did not improve pCR rates (13.2% for TAC+ZA versus 13.3% for TAC). Postmenopausal women (N = 96) had a numerical benefit from ZA treatment (pCR 14.0% for TAC+ZA versus 8.7% for TAC, P = 0.42). Clinical objective response did not differ between treatment arms (72.9% versus 73.7%). There was no difference in grade III/IV toxicity between treatment arms. Addition of ZA to neoadjuvant chemotherapy did not improve pathological or clinical response to chemotherapy. Further investigations are warranted in postmenopausal women with BC, since this subgroup might benefit from ZA treatment.

Sustained-release bupropion versus naltrexone in the treatment of pathological gambling: a preliminary blind-rater study.

PubMed

Dannon, Pinhas N; Lowengrub, Katherine; Musin, Ernest; Gonopolski, Yehudit; Kotler, Moshe

2005-12-01

Pathological gambling (PG) is a relatively common and highly disabling impulse control disorder. A range of psychotherapeutic agents, including selective serotonin reuptake inhibitors, mood stabilizers, and opioid antagonists, has been shown to be effective in the treatment of PG. The use of selective serotonin reuptake inhibitors and opioid antagonists for PG is consistent with the observation that PG shares features of both the obsessive-compulsive spectrum disorders and addictive disorders. The aim of the study is to compare the effectiveness of sustained-release bupropion versus naltrexone in the treatment of PG. Thirty-six male pathological gamblers were enrolled in our study. A comprehensive psychiatric diagnostic evaluation was performed at baseline on all patients, and patients were screened for symptoms of gambling, depression, and anxiety using the South Oaks Gambling Screen, the Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, and the Clinical Global Impression-Severity Scale. In addition, the patients completed self-report questionnaires about their demographic status. Patients were randomized in 2 groups and received either naltrexone (n = 19) or sustained-release bupropion (n = 17) for 12 weeks in a parallel fashion. Treatment response was monitored using the Clinical Global Impression-Improvement Scale which was performed at weeks 2, 4, 8, and 12. Patients were also assessed for the presence of gambling behavior via an unstructured interview, which was also performed at weeks 2, 4, 6, 8, and 12. Raters were blind to the study treatment. The majority of patients responded well to the drug treatment. Twelve of 17 patients in the sustained-release bupropion group completed the 12-week study, and 13 of 19 naltrexone patients completed the study. Nine (75%) of the 12 completers were rated as full responders in the sustained-release bupropion group versus 10 (76%) of 12 in the naltrexone group. Three (25%) of 12 completers in the bupropion group were rated as partial responders. In the naltrexone group, 3 (23%) of 13 completers were rated as partial responders. Full response was defined as the absence of gambling for a 2-week duration together with improvement on the Clinical Global Impression-Improvement Scale. Partial response was defined as a decrease in the frequency of gambling behavior and a decrease in the amount of money spent on gambling. This preliminary study shows that sustained-release bupropion may be effective as naltrexone in the treatment of PG. Further studies are needed to confirm our findings.

Preoperative Chemoradiation With Cetuximab, Irinotecan, and Capecitabine in Patients With Locally Advanced Resectable Rectal Cancer: A Multicenter Phase II Study

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

Kim, Sun Young; Hong, Yong Sang; Kim, Dae Yong

Purpose: To evaluate the efficacy and safety of preoperative chemoradiation with cetuximab, irinotecan, and capecitabine in patients with rectal cancer. Methods and Materials: Forty patients with locally advanced, nonmetastatic, and mid- to lower rectal cancer were enrolled. Radiotherapy was delivered at a dose of 50.4 Gy/28 fractions. Concurrent chemotherapy consisted of an initial dose of cetuximab of 400 mg/m{sup 2} 1 week before radiotherapy, and then cetuximab 250 mg/m{sup 2}/week, irinotecan 40 mg/m{sup 2}/week for 5 consecutive weeks and capecitabine 1,650 mg/m{sup 2}/day for 5 days a week (weekdays only) from the first day during radiotherapy. Total mesorectal excision wasmore » performed within 6 {+-} 2 weeks. The pathologic responses and survival outcomes were evaluated as study endpoints, and an additional KRAS mutation analysis was performed. Results: In total, 39 patients completed their planned preoperative chemoradiation and underwent R0 resection. The pathologic complete response rate was 23.1% (9/39), and 3 patients (7.7%) showed near total regression of tumor. The 3-year disease-free and overall survival rates were 80.0% and 94.7%, respectively. Grade 3/4 toxicities included leukopenia (4, 10.3%), neutropenia (2, 5.1%), anemia (1, 2.6%), diarrhea (2, 5.1%), fatigue (1, 2.6%), skin rash (1, 2.6%), and ileus (1, 2.6%). KRAS mutations were found in 5 (13.2%) of 38 patients who had available tissue for testing. Clinical outcomes were not significantly correlated with KRAS mutation status. Conclusions: Preoperative chemoradiation with cetuximab, irinotecan, and capecitabine was active and well tolerated. KRAS mutation status was not a predictive factor for pathologic response in this study.« less

The Benefit of Chemotherapy in Esophageal Cancer Patients With Residual Disease After Trimodality Therapy.

PubMed

Kim, Grace J; Koshy, Matthew; Hanlon, Alexandra L; Horiba, M Naomi; Edelman, Martin J; Burrows, Whitney M; Battafarano, Richard J; Suntharalingam, Mohan

2016-04-01

The objective of this retrospective study was to determine the potential benefits of chemotherapy in esophageal cancer patients treated with chemoradiation followed by surgery. At our institution, 145 patients completed trimodality therapy from 1993 to 2009. Neoadjuvant treatment predominantly consisted of 5-fluorouracil and cisplatin with a concurrent median radiation dose of 50.4 Gy. Sixty-two patients received chemotherapy postoperatively. The majority (49/62) received 3 cycles of docetaxel. Within the entire cohort, a 5-year overall survival (OS) benefit was found in those who received postoperative chemotherapy, OS 37.1% versus 18.0% (P=0.024). The response after neoadjuvant chemoradiation was as follows: 33.8% had a pathologic complete response and 62.8% with residual disease. A 5-year OS and cause-specific survival (CSS) advantage were associated with postoperative chemotherapy among those with macroscopic residual disease after neoadjuvant therapy: OS 38.7% versus 13.9% (P=0.016), CSS 42.8% versus 18.8% (P=0.048). This benefit was not seen in those with a pathologic complete response or those with microscopic residual. A stepwise multivariate Cox regression model evaluating the partial response group revealed that postoperative chemotherapy and M stage were independent predictors of overall and CSS. This analysis revealed that patients with gross residual disease after trimodality therapy for esophageal cancer who received postoperative chemotherapy had an improved overall and CSS. These data suggest that patients with residual disease after trimodality therapy and a reasonable performance status may benefit from postoperative chemotherapy. Prospective trials are needed to confirm these results to define the role of postoperative treatment after trimodality therapy.

Culturally diverse attitudes and beliefs of students majoring in speech-language pathology.

PubMed

Franca, Maria Claudia; Smith, Linda McCabe; Nichols, Jane Luanne; Balan, Dianna Santos

Academic education in speech-language pathology should prepare students to provide professional services that mirror current knowledge, skills, and scope of practice in a pluralistic society. This study seeks to examine the impact of speech-language pathology (SLP) students prior multicultural experiences and previous formal education on attitudes and beliefs toward language diversity. A survey to investigate SLP students attitudes toward language diversity was applied. After the research study and instructions to complete the consent form questionnaire was presented by a research assistant, an announcement was given by a graduate student who speaks English as a second language with an accent. The participants then completed a questionnaire containing questions related to attitudes about the presentation of the announcement in particular and toward language diversity in general. Responses suggested a relationship between self-reported cultural bias and ability to concentrate on speech with an accent, and the extent of interaction with individuals from a cultural and linguistic diverse (CLD) background. Additional outcomes revealed that cultural bias may be predicted by factors related to amount of CLD exposure. Results of this study indicated critical areas that need to be considered when developing curricula in speech-language pathology programs. The results will be useful in determining procedures applicable in larger investigations, and encourage future research on attitudes and beliefs toward aspects of cultural diversity.

77 FR 31858 - Draft Guidance for Industry on Pathologic Complete Response in Neoadjuvant Treatment of High-Risk...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-30

... approval regulations. Despite advances in systemic therapy of early-stage breast cancer over the past few... systemic therapy of breast cancer over the past few decades, there remains a significant unmet medical need... any person and does not operate to bind FDA or the public. An alternative approach may be used if such...

The Influence of Supplementary Multimedia Instruction on Students' Knowledge of Normal Swallowing: An Authentic Investigation Over Time.

ERIC Educational Resources Information Center

Scholten, Ingrid

This paper describes the effect of supplementary multimedia instruction on the pattern of growth of student learning of normal swallowing. On four occasions, up to 190 speech pathology students from four Australian universities completed a free-response task designed to assess students' learning of core information. Scripts were scored using a…

Preoperative chemoradiotherapy with 5-fluorouracil and oxaliplatin for locally advanced rectal cancer: long-term results of a phase II trial.

PubMed

Liu, Luying; Cao, Caineng; Zhu, Yuan; Li, Dechuan; Feng, Haiyang; Luo, Jialin; Tang, Zhongzhu; Liu, Peng; Lu, Ke; Ju, Haixing; Zhang, Na

2015-03-01

The aim of this study was to report long-term results of patients with locally advanced rectal cancer treated by neoadjuvant chemoradiotherapy with fluorouracil, leucovorin, and oxaliplatin. From February 2002 to November 2006, a total of 58 patients with locally advanced rectal cancer were recruited. Secondary endpoints included the cumulative incidence of local and distant recurrences, disease-free survival, and overall survival. The median follow-up time was 138 months (109-151 months). The cumulative incidence of local recurrence at 10 years was 12.1%. The cumulative incidence of distant recurrence at 10 years was 53.4%. The overall survival in the intention-to-treat population was 39.5% at 10 years. Disease-free survival in the intention-to-treat population was 41.8% at 10 years. Univariate analysis revealed that pathologic complete response was associated with local recurrence, distant recurrence, disease-free survival, and overall survival (p < .05). Distant recurrence remains the predominant pattern of failure for patients with locally advanced rectal cancer after preoperative chemoradiotherapy and total mesorectal excision. Pathologic complete response is an independent prognostic factor for locally advanced rectal cancer after preoperative chemoradiotherapy.

Recommendations for standardized pathological characterization of residual disease for neoadjuvant clinical trials of breast cancer by the BIG-NABCG collaboration.

PubMed

Bossuyt, V; Provenzano, E; Symmans, W F; Boughey, J C; Coles, C; Curigliano, G; Dixon, J M; Esserman, L J; Fastner, G; Kuehn, T; Peintinger, F; von Minckwitz, G; White, J; Yang, W; Badve, S; Denkert, C; MacGrogan, G; Penault-Llorca, F; Viale, G; Cameron, D

2015-07-01

Neoadjuvant systemic therapy (NAST) provides the unique opportunity to assess response to treatment after months rather than years of follow-up. However, significant variability exists in methods of pathologic assessment of response to NAST, and thus its interpretation for subsequent clinical decisions. Our international multidisciplinary working group was convened by the Breast International Group-North American Breast Cancer Group (BIG-NABCG) collaboration and tasked to recommend practical methods for standardized evaluation of the post-NAST surgical breast cancer specimen for clinical trials that promote accurate and reliable designation of pathologic complete response (pCR) and meaningful characterization of residual disease. Recommendations include multidisciplinary communication; clinical marking of the tumor site (clips); and radiologic, photographic, or pictorial imaging of the sliced specimen, to map the tissue sections and reconcile macroscopic and microscopic findings. The information required to define pCR (ypT0/is ypN0 or ypT0 yp N0), residual ypT and ypN stage using the current AJCC/UICC system, and the Residual Cancer Burden system were recommended for quantification of residual disease in clinical trials. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Response to treatment and interval to surgery after preoperative short-course radiotherapy in rectal cancer.

PubMed

García-Cabezas, Sonia; Rodríguez-Liñán, Milagrosa; Otero-Romero, Ana M; Bueno-Serrano, Carmen M; Gómez-Barbadillo, José; Palacios-Eito, Amalia

2016-10-01

Preoperative short-course radiotherapy with immediate surgery improves local control in patients with rectal cancer. Tumor responses are smaller than those described with radiochemotherapy. Preliminary data associate this lower response to the short period until surgery. The aim of this study is to analyze the response to preoperative short-course radiotherapy and its correlation with the interval to surgery especially analyzing patients with mesorectal fascia involvement. A total of 155 patients with locally advanced rectal cancer treated with preoperative radiotherapy (5×5Gy) were retrospectively analyzed. Tumor response in terms of rates of complete pathological response, downstaging, tumor regression grading and status of the circumferential resection margin were quantified. The mean interval from radiotherapy to surgery was 23 days. The rate of complete pathological response was 2.2% and 28% experienced downstaging (stage decreased). No differences between these rates and interval to surgery were detected. Eighty-eight patients had magnetic resonance imaging for staging (in 31 patients the mesorectal fascia was involved).The mean time to surgery in patients with involvement of the fascia and R0 surgery was 27 days and 16 days if R1 (P=.016). The cutoff of 20 days reached the highest probability of achieving a free circumferential resection margin between patients with mesorectal fascia involvement, with no statistically significant differences: RR 3.036 95% CI=(0.691-13.328), P=.06. After preoperative short-course radiotherapy, an interval>20 days enhances the likelihood of achieving a free circumferential resection margin in patients with mesorectal fascia involvement. Copyright © 2016 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

Quantitative contrast-enhanced ultrasound evaluation of pathological complete response in patients with locally advanced breast cancer receiving neoadjuvant chemotherapy.

PubMed

Wan, Cai-Feng; Liu, Xue-Song; Wang, Lin; Zhang, Jie; Lu, Jin-Song; Li, Feng-Hua

2018-06-01

To clarify whether the quantitative parameters of contrast-enhanced ultrasound (CEUS) can be used to predict pathological complete response (pCR) in patients with locally advanced breast cancer receiving neoadjuvant chemotherapy (NAC). Fifty-one patients with histologically proved locally advanced breast cancer scheduled for NAC were enrolled. The quantitative data for CEUS and the tumor diameter were collected at baseline and before surgery, and compared with the pathological response. Multiple logistic regression analysis was performed to examine quantitative parameters at CEUS and the tumor diameter to predict the pCR, and receiver operating characteristic (ROC) curve analysis was used as a summary statistic. Multiple logistic regression analysis revealed that PEAK (the maximum intensity of the time-intensity curve during bolus transit), PEAK%, TTP% (time to peak), and diameter% were significant independent predictors of pCR, and the area under the ROC curve was 0.932(Az 1 ), and the sensitivity and specificity to predict pCR were 93.7% and 80.0%. The area under the ROC curve for the quantitative parameters was 0.927(Az 2 ), and the sensitivity and specificity to predict pCR were 81.2% and 94.3%. For diameter%, the area under the ROC curve was 0.786 (Az 3 ), and the sensitivity and specificity to predict pCR were 93.8% and 54.3%. The values of Az 1 and Az 2 were significantly higher than that of Az 3 (P = 0.027 and P = 0.034, respectively). However, there was no significant difference between the values of Az 1 and Az 2 (P = 0.825). Quantitative analysis of tumor blood perfusion with CEUS is superior to diameter% to predict pCR, and can be used as a functional technique to evaluate tumor response to NAC. Copyright © 2018. Published by Elsevier B.V.

Career Paths of Pathology Informatics Fellowship Alumni.

PubMed

Rudolf, Joseph W; Garcia, Christopher A; Hanna, Matthew G; Williams, Christopher L; Balis, Ulysses G; Pantanowitz, Liron; Tuthill, J Mark; Gilbertson, John R

2018-01-01

The alumni of today's Pathology Informatics and Clinical Informatics fellowships fill diverse roles in academia, large health systems, and industry. The evolving training tracks and curriculum of Pathology Informatics fellowships have been well documented. However, less attention has been given to the posttraining experiences of graduates from informatics training programs. Here, we examine the career paths of subspecialty fellowship-trained pathology informaticians. Alumni from four Pathology Informatics fellowship training programs were contacted for their voluntary participation in the study. We analyzed various components of training, and the subsequent career paths of Pathology Informatics fellowship alumni using data extracted from alumni provided curriculum vitae. Twenty-three out of twenty-seven alumni contacted contributed to the study. A majority had completed undergraduate study in science, technology, engineering, and math fields and combined track training in anatomic and clinical pathology. Approximately 30% (7/23) completed residency in a program with an in-house Pathology Informatics fellowship. Most completed additional fellowships (15/23) and many also completed advanced degrees (10/23). Common primary posttraining appointments included chief medical informatics officer (3/23), director of Pathology Informatics (10/23), informatics program director (2/23), and various roles in industry (3/23). Many alumni also provide clinical care in addition to their informatics roles (14/23). Pathology Informatics alumni serve on a variety of institutional committees, participate in national informatics organizations, contribute widely to scientific literature, and more than half (13/23) have obtained subspecialty certification in Clinical Informatics to date. Our analysis highlights several interesting phenomena related to the training and career trajectory of Pathology Informatics fellowship alumni. We note the long training track alumni complete in preparation for their careers. We believe flexible training pathways combining informatics and clinical training may help to alleviate the burden. We highlight the importance of in-house Pathology Informatics fellowships in promoting interest in informatics among residents. We also observe the many important leadership roles in academia, large community health systems, and industry available to early career alumni and believe this reflects a strong market for formally trained informaticians. We hope this analysis will be useful as we continue to develop the informatics fellowships to meet the future needs of our trainees and discipline.

Intratumor partitioning and texture analysis of dynamic contrast-enhanced (DCE)-MRI identifies relevant tumor subregions to predict pathological response of breast cancer to neoadjuvant chemotherapy.

PubMed

Wu, Jia; Gong, Guanghua; Cui, Yi; Li, Ruijiang

2016-11-01

To predict pathological response of breast cancer to neoadjuvant chemotherapy (NAC) based on quantitative, multiregion analysis of dynamic contrast enhancement magnetic resonance imaging (DCE-MRI). In this Institutional Review Board-approved study, 35 patients diagnosed with stage II/III breast cancer were retrospectively investigated using 3T DCE-MR images acquired before and after the first cycle of NAC. First, principal component analysis (PCA) was used to reduce the dimensionality of the DCE-MRI data with high temporal resolution. We then partitioned the whole tumor into multiple subregions using k-means clustering based on the PCA-defined eigenmaps. Within each tumor subregion, we extracted four quantitative Haralick texture features based on the gray-level co-occurrence matrix (GLCM). The change in texture features in each tumor subregion between pre- and during-NAC was used to predict pathological complete response after NAC. Three tumor subregions were identified through clustering, each with distinct enhancement characteristics. In univariate analysis, all imaging predictors except one extracted from the tumor subregion associated with fast washout were statistically significant (P < 0.05) after correcting for multiple testing, with area under the receiver operating characteristic (ROC) curve (AUC) or AUCs between 0.75 and 0.80. In multivariate analysis, the proposed imaging predictors achieved an AUC of 0.79 (P = 0.002) in leave-one-out cross-validation. This improved upon conventional imaging predictors such as tumor volume (AUC = 0.53) and texture features based on whole-tumor analysis (AUC = 0.65). The heterogeneity of the tumor subregion associated with fast washout on DCE-MRI predicted pathological response to NAC in breast cancer. J. Magn. Reson. Imaging 2016;44:1107-1115. © 2016 International Society for Magnetic Resonance in Medicine.

Effects of neoadjuvant chemotherapy with or without zoledronic acid on pathological response: A meta-analysis of randomised trials.

PubMed

Kroep, J R; Charehbili, A; Coleman, R E; Aft, R L; Hasegawa, Y; Winter, M C; Weilbaecher, K; Akazawa, K; Hinsley, S; Putter, H; Liefers, G J; Nortier, J W R; Kohno, N

2016-02-01

The addition of bisphosphonates to adjuvant therapy improves survival in postmenopausal breast cancer (BC) patients. We report a meta-analysis of four randomised trials of neoadjuvant chemotherapy (CT) +/- zoledronic acid (ZA) in stage II/III BC to investigate the potential for enhancing the pathological response. Individual patient data from four prospective randomised clinical trials reporting the effect of the addition of ZA on the pathological response after neoadjuvant CT were pooled. Primary outcomes were pathological complete response in the breast (pCRb) and in the breast and lymph nodes (pCR). Trial-level and individual patient data meta-analyses were done. Predefined subgroup-analyses were performed for postmenopausal women and patients with triple-negative BC. pCRb and pCR data were available in 735 and 552 patients respectively. In the total study population ZA addition to neoadjuvant CT did not increase pCRb or pCR rates. However, in postmenopausal patients, the addition of ZA resulted in a significant, near doubling of the pCRb rate (10.8% for CT only versus 17.7% with CT+ZA; odds ratio [OR] 2.14, 95% confidence interval [CI] 1.01-4.55) and a non-significant benefit of the pCR rate (7.8% for CT only versus 14.6% with CT+ZA; OR 2.62, 95% CI 0.90-7.62). In patients with triple-negative BC a trend was observed favouring CT+ZA. This meta-analysis shows no impact from the addition of ZA to neoadjuvant CT on pCR. However, as has been seen in the adjuvant setting, the addition of ZA to neoadjuvant CT may augment the effects of CT in postmenopausal patients with BC. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Patient and tumor characteristics associated with breast cancer recurrence after complete pathological response to neoadjuvant chemotherapy.

PubMed

Ju, Na Rae; Jeffe, Donna B; Keune, Jason; Aft, Rebecca

2013-01-01

Breast cancer patients whose tumors achieve a pathological complete response (pCR) with neoadjuvant chemotherapy have a prognosis which is better than that predicted for the stage of their disease. However, within this subgroup of patients, recurrences have been observed. We sought to examine factors associated with recurrence in a population of breast cancer patients who achieved a pCR with neoadjuvant chemotherapy. A retrospective chart review was conducted of all patients with unilateral breast cancer treated with neoadjuvant chemotherapy from January 1, 2000 to December 31, 2010 at one comprehensive cancer center. A pCR was defined as no residual invasive cancer in the breast in the surgical specimen following neoadjuvant therapy. Recurrence was defined as visceral or bony reappearance of cancer after completion of all therapy. Of 818 patients who completed neoadjuvant chemotherapy, 144 (17.6 %) had pCR; six with bilateral breast cancer were excluded from further analysis. The mean time to follow-up was 47.2 months. Among the 138 patients with unilateral breast cancer, there were 14 recurrences (10.1 %). Using a binary multiple logistic regression model, examining types of chemotherapy and surgery, race, lymph node assessment, and lymph node status, breast cancer side, triple-negative status, and radiation receipt, only African-American patients (OR: 5.827, 95 % CI: 1.280-26.525; p = 0.023) were more likely to develop distant recurrence. The mean time to recurrence was 31.9 months. In our study, race was the only independent predictor of recurrence after achieving pCR with neoadjuvant chemotherapy. The reasons for this observation require further study.

Gene expression levels of gamma-glutamyl hydrolase in tumor tissues may be a useful biomarker for the proper use of S-1 and tegafur-uracil/leucovorin in preoperative chemoradiotherapy for patients with rectal cancer.

PubMed

Sadahiro, Sotaro; Suzuki, T; Tanaka, A; Okada, K; Saito, G; Miyakita, H; Ogimi, T; Nagase, H

2017-06-01

Preoperative chemoradiotherapy (CRT) using 5-fluorouracil (5-FU)-based chemotherapy is the standard of care for rectal cancer. The effect of additional chemotherapy during the period between the completion of radiotherapy and surgery remains unclear. Predictive factors for CRT may differ between combination chemotherapy with S-1 and with tegafur-uracil/leucovorin (UFT/LV). The subjects were 54 patients with locally advanced rectal cancer who received preoperative CRT with S-1 or UFT/LV. The pathological tumor response was assessed according to the tumor regression grade (TRG). The expression levels of 18 CRT-related genes were determined using RT-PCR assay. A pathological response (TRG 1-2) was observed in 23 patients (42.6%). In a multivariate logistic regression analysis for pathological response, the overall expression levels of four genes, HIF1A, MTHFD1, GGH and TYMS, were significant, and the accuracy rate of the predictive model was 83.3%. The effects of the gene expression levels of GGH on the response differed significantly according to the treatment regimen. The total pathological response rate of both high-GGH patients in the S-1 group and low-GGH patients in the UFT/LV group was 58.3%. Additional treatment with 5-FU-based chemotherapy during the interval between radiotherapy and surgery is not beneficial in patients who have received 5-FU-based CRT. The expression levels of four genes, HIF1A, MTHFD1, GGH and TYMS, in tumor tissues can predict the response to preoperative CRT including either S-1 or UFT/LV. In particular, the gene expression level of GGH in tumor tissues may be a useful biomarker for the appropriate use of S-1 and UFT/LV in CRT.

Correlation of tumor response on computed tomography with pathological necrosis in hepatocellular carcinoma treated by chemoembolization before liver transplantation.

PubMed

Dioguardi Burgio, Marco; Ronot, Maxime; Bruno, Onorina; Francoz, Claire; Paradis, Valérie; Castera, Laurent; Durand, François; Soubrane, Olivier; Vilgrain, Valérie

2016-11-01

The purpose of this article was to compare the results of Response Evaluation Criteria in Solid Tumors (RECIST), modified Response Evaluation Criteria in Solid Tumors (mRECIST), and European Association for the Study of the Liver (EASL) criteria for the evaluation of tumor necrosis in patients treated with transarterial chemoembolization before liver transplantation (LT) for hepatocellular carcinoma. Response to treatment was evaluated on computed tomography scan by 2 independent readers based on RECIST, mRECIST, and EASL criteria, and compared with tumor necrosis assessed by explant pathology. Necrosis was defined as major when >90%. Factors associated with major necrosis were tested by multivariate analysis. Fifty-eight patients (53 males; mean age, 54 years; range, 31-64 years) were included with 88 nodules. Fifty-one (58%) nodules were shown to have major necrosis. Among them readers 1 and 2 identified a complete response (CR) according to RECIST, mRECIST, and EASL criteria in 2 (4%), 47 (92%), and 47 (92%), and 1 (2%), 45 (88%), and 45 (88%) nodules, respectively. However, 12-14 of 59 nodules classified as CR on mRECIST or EASL criteria were found to have intermediate or minor necrosis (overestimation in 20%-24% of the patients). Combining the classification of CR by mRECIST and EASL criteria and complete lipiodol deposition reduced the overestimation to 11%. Among 59 nodules classified with a CR according to mRECIST or EASL, those with complete lipiodol deposition (n = 36, 61%) had a higher rate of necrosis than those with incomplete lipiodol deposition (n = 23, 39%): 95% versus 68% and 95% versus 63% for reader 1 and 2, respectively. In conclusion, CR based on mRECIST/EASL combined with complete lipiodol deposition was better for identification of major tumor necrosis. Even in the presence of CR according to mRECIST/EASL, incomplete lipiodol deposition should be considered indicative of substantial viable tumor remnant. Liver Transplantation 22 1491-1500 2016 AASLD. © 2016 by the American Association for the Study of Liver Diseases.

Integrated Genomic Biomarkers to Identify Aggressive Disease in African Americans with Prostate Cancer

DTIC Science & Technology

2016-09-01

300 of these men; have completed pathology review of 70 of the discovery sample tumors; macrodissected and performed DNA extraction from 50 tumors...block, and sections cut and tumor areas marked by histopathologist. Target completion September 1st 2017; Discovery sample 35% completed Pathology ...African American population. Target completion March 2017; 50% completed. What was accomplished under these goals? In the current reporting

[Eosinophilic esophagitis, a pathology on the rise].

PubMed

Miranda García, M; Gutiérrez Teira, B

2013-10-01

The eosinophilic esofagitis is a pathology that consists of an inflammatory condition of the esophagus, which is characterized for having a high percentage of eosinophils. It is a problem of allergic origin and his diagnosis is increasing in the population, especially in children and adult young persons, throughout last decade. The fisiopathology is not completely established nowadays. The diagnosis is confirmed with endoscopia and capture of biopsies. The differential diagnosis is necessary to be done with the disease for reflux gastroesofágico, gastroenteritis eosinofílica, by Crohn's disease, pathology of connective fabric, syndrome hipereosinofílico, infections and response of hypersensitivity to medicaments. Nowadays there is no a treatment that is definitive. We present a clinical case, which was valued initially for the consultation of Primary care. Copyright © 2011 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

Core components of a comprehensive quality assurance program in anatomic pathology.

PubMed

Nakhleh, Raouf E

2009-11-01

In this article the core components of a comprehensive quality assurance and improvement plan are outlined. Quality anatomic pathology work comes with focus on accurate, timely, and complete reports. A commitment to continuous quality improvement and a systems approach with a persistent effort helps to achieve this end. Departments should have a quality assurance and improvement plan that includes a risk assessment of real and potential problems facing the laboratory. The plan should also list the individuals responsible for carrying out the program with adequate resources, a defined timetable, and annual assessment for progress and future directions. Quality assurance monitors should address regulatory requirements and be organized by laboratory division (surgical pathology, cytology, etc) as well as 5 segments (preanalytic, analytic, postanalytic phases of the test cycle, turn-around-time, and customer satisfaction). Quality assurance data can also be used to evaluate individual pathologists using multiple parameters with peer group comparison.

[A Case Report of Disappearance of Gastric Metastasis of Breast Cancer Treated with Combination Therapy Consisting of Paclitaxel and Cisplatin].

PubMed

Nakajima, Tooru; Taniwaka, Koichi; Goto, Hideki; Kawamura, Shunji

2017-04-01

A 63-year-old postmenopausal woman was treated with combination therapy consisting of paclitaxel(PTX)and cisplatin (CDDP)for gastric metastasis of breast cancer; she achieved a complete response as revealed by pathological examination. Combination therapy with PTX and CDDP seems to be an optional treatment for gastric metastasis of breast cancer.

A Phase I Study of UFT/Leucovorin, Carboplatin, and Paclitaxel in Combination With External Beam Radiation Therapy for Advanced Esophageal Carcinoma

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

Czito, Brian G.; Cohen, Darrel P.; Kelsey, Chris R.

Purpose: Concurrent chemotherapy and radiation therapy (RT) are used to treat patients with esophageal cancer. The optimal combination of chemotherapeutic agents with RT is not well established. We evaluated the safety and preliminary efficacy of a combination of UFT/leucovorin, carboplatin, and paclitaxel with RT in a Phase I study of patients with advanced esophageal cancer. Methods and Materials: Patients with squamous cell carcinoma or adenocarcinoma of the esophagus initially received UFT/leucovorin, carboplatin, and paclitaxel with RT (1.8 Gy daily to 45 Gy). After completion, the disease was restaged and patients were evaluated for surgery. Primary end points included determination ofmore » dose-limiting toxicities (DLTs) and a recommended Phase II dose. Secondary objectives included determination of non-DLTs, as well as preliminary radiographic and pathologic response rates. Results: Twelve patients were enrolled (11 men, 1 woman). All were assessable for toxicity and efficacy. One of 6 patients at Dose Level 1 (UFT/leucovorin, 200/30 mg twice daily on RT days; carboplatin, area under the curve [AUC] 5, Weeks 1 and 4; paclitaxel, 175 mg/m{sup 2} Weeks 1 and 4) had a DLT (febrile neutropenia). Of these 6 patients, 4 underwent esophagectomy and none achieved a pathologic complete response. Six patients were then enrolled at Dose Level 2 (UFT/leucovorin, 300/30 mg in the morning and 200/30 mg in the evening on RT days; carboplatin, AUC 5, Weeks 1 and 4; paclitaxel, 175 mg/m{sup 2} Weeks 1 and 4). Two of 6 patients at Dose Level 2 developed DLTs (febrile neutropenia in both). Esophagectomy was performed in 3 patients, with 2 achieving a pathologic complete response. Conclusions: Maximum tolerated doses in this study were UFT/leucovorin, 200/30 mg twice daily on RT days; carboplatin, AUC 5, Weeks 1 and 4; and paclitaxel, 175 mg/m{sup 2} Weeks 1 and 4 when delivered with external RT. In this small study, this regimen appears active, but toxic.« less

A deep learning classifier for prediction of pathological complete response to neoadjuvant chemotherapy from baseline breast DCE-MRI

NASA Astrophysics Data System (ADS)

Ravichandran, Kavya; Braman, Nathaniel; Janowczyk, Andrew; Madabhushi, Anant

2018-02-01

Neoadjuvant chemotherapy (NAC) is routinely used to treat breast tumors before surgery to reduce tumor size and improve outcome. However, no current clinical or imaging metrics can effectively predict before treatment which NAC recipients will achieve pathological complete response (pCR), the absence of residual invasive disease in the breast or lymph nodes following surgical resection. In this work, we developed and applied a convolu- tional neural network (CNN) to predict pCR from pre-treatment dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) scans on a per-voxel basis. In this study, DCE-MRI data for a total of 166 breast cancer pa- tients from the ISPY1 Clinical Trial were split into a training set of 133 patients and a testing set of 33 patients. A CNN consisting of 6 convolutional blocks was trained over 30 epochs. The pre-contrast and post-contrast DCE-MRI phases were considered in isolation and conjunction. A CNN utilizing a combination of both pre- and post-contrast images best distinguished responders, with an AUC of 0.77; 82% of the patients in the testing set were correctly classified based on their treatment response. Within the testing set, the CNN was able to produce probability heatmaps that visualized tumor regions that most strongly predicted therapeutic response. Multi- variate analysis with prognostic clinical variables (age, largest diameter, hormone receptor and HER2 status), revealed that the network was an independent predictor of response (p=0.05), and that the inclusion of HER2 status could further improve capability to predict response (AUC = 0.85, accuracy = 85%).

Assessing residual cancer cells using MRI and US after preoperative chemotherapy in primary breast cancer to omit surgery.

PubMed

Iwase, Madoka; Sawaki, Masataka; Hattori, Masaya; Yoshimura, Akiyo; Ishiguro, Junko; Kotani, Haruru; Gondo, Naomi; Adachi, Yayoi; Kataoka, Ayumi; Onishi, Sakura; Sugino, Kayoko; Iwata, Hiroji

2018-04-04

Enhanced magnetic resonance imaging (MRI) and ultrasonography (US) are used to assess residual lesions after preoperative chemotherapy before surgery. However, residual lesion assessments based on preoperative imaging often differ from postoperative pathologic diagnoses. We retrospectively reviewed the accuracy of preoperative residual lesion assessments, including ductal carcinoma in situ (DCIS) cases to find criteria for cases in which surgery can be omitted. We reviewed 201 patients who received preoperative chemotherapy and surgery in our hospital from January 2013 to November 2016. Presurgical evaluations regarding the possible existence of residual lesions, and clinical Complete Response (cCR) or non-cCR, were compared with postoperative pathological diagnoses. Of the 201 patients, 52 were diagnosed with cCR, and 39 with pathological complete response (pCR). Predictions for residual lesions were 86.4% sensitive, 76.9% specific, and 84.6% accurate. When patients were divided into 4 groups by estrogen receptor (ER) and HER2 status, sensitivity in each group was ER + /HER2 - : 91.4%; ER - /HER2 - : 94.1%; ER + /HER2 + : 78.6%; and ER - /HER2 + : 78.5%. Of the 22 patients preoperatively assessed with cCR, but diagnosed with non-pCR, the median invasive residual tumor size was 2 mm (range 0-46 mm); 5 patients (22.7%) had only DCIS. Predicting residual lesions after preoperative chemotherapy by using MRI and US is a reasonable strategy. However, current methods are inadequate for identifying patients who can omit surgery; therefore, a new strategy for detecting small tumors in these patients is needed.

Pathologic response after preoperative therapy predicts prognosis of Chinese colorectal cancer patients with liver metastases.

PubMed

Wang, Yun; Yuan, Yun-Fei; Lin, Hao-Cheng; Li, Bin-Kui; Wang, Feng-Hua; Wang, Zhi-Qiang; Ding, Pei-Rong; Chen, Gong; Wu, Xiao-Jun; Lu, Zhen-Hai; Pan, Zhi-Zhong; Wan, De-Sen; Sun, Peng; Yan, Shu-Mei; Xu, Rui-Hua; Li, Yu-Hong

2017-10-02

Pathologic response is evaluated according to the extent of tumor regression and is used to estimate the efficacy of preoperative treatment. Several studies have reported the association between the pathologic response and clinical outcomes of colorectal cancer patients with liver metastases who underwent hepatectomy. However, to date, no data from Chinese patients have been reported. In this study, we aimed to evaluate the association between the pathologic response to pre-hepatectomy chemotherapy and prognosis in a cohort of Chinese patients. In this retrospective study, we analyzed the data of 380 liver metastases in 159 patients. The pathologic response was evaluated according to the tumor regression grade (TRG). The prognostic role of pathologic response in recurrence-free survival (RFS) and overall survival (OS) was assessed using Kaplan-Meier curves with the log-rank test and multivariate Cox models. Factors that had potential influence on pathologic response were also analyzed using multivariate logistic regression and Kruskal-Wallis/Mann-Whitney U tests. Patients whose tumors achieved pathologic response after preoperative chemotherapy had significant longer RFS and OS than patients whose tumor had no pathologic response to chemotherapy (median RFS: 9.9 vs. 6.5 months, P = 0.009; median OS: 40.7 vs. 28.1 months, P = 0.040). Multivariate logistic regression and Kruskal-Wallis/Mann-Whitney U tests showed that metastases with small diameter, metastases from the left-side primary tumors, and metastases from patients receiving long-duration chemotherapy had higher pathologic response rates than their control metastases (all P < 0.05). A decrease in the serum carcinoembryonic antigen (CEA) level after preoperative chemotherapy predicted an increased pathologic response rate (P < 0.05). Although the application of targeted therapy did not significantly influence TRG scores of all cases of metastases, the addition of cetuximab to chemotherapy resulted in a higher pathologic response rate when combined with irinotecan-based regimens rather than with oxaliplatin-based regimens. We found that the evaluation of pathologic response may predict the prognosis of Chinese colorectal cancer patients with liver metastases after preoperative chemotherapy. Small tumor diameter, long-duration chemotherapy, left primary tumor, and decreased serum CEA level after chemotherapy are associated with increased pathologic response rates.

Validation of Patient-Reported Outcomes Measurement Information System Computerized Adaptive Tests Against the Foot and Ankle Outcome Score for 6 Common Foot and Ankle Pathologies.

PubMed

Koltsov, Jayme C B; Greenfield, Stephen T; Soukup, Dylan; Do, Huong T; Ellis, Scott J

2017-08-01

The field of foot and ankle surgery lacks a widely accepted gold-standard patient-reported outcome instrument. With the changing infrastructure of the medical profession, more efficient patient-reported outcome tools are needed to reduce respondent burden and increase participation while providing consistent and reliable measurement across multiple pathologies and disciplines. The primary purpose of the present study was to validate 3 Patient-Reported Outcomes Measurement Information System computer adaptive tests (CATs) most relevant to the foot and ankle discipline against the Foot and Ankle Outcome Score (FAOS) and the Short Form 12 general health status survey in patients with 6 common foot and ankle pathologies. Patients (n = 240) indicated for operative treatment for 1 of 6 common foot and ankle pathologies completed the CATs, FAOS, and Short Form 12 at their preoperative surgical visits, 1 week subsequently (before surgery), and at 6 months postoperatively. The psychometric properties of the instruments were assessed and compared. The Patient-Reported Outcomes Measurement Information System CATs each took less than 1 minute to complete, whereas the FAOS took 6.5 minutes, and the Short Form 12 took 3 minutes. CAT scores were more normally distributed and had fewer floor and ceiling effects than those on the FAOS, which reached as high as 24%. The CATs were more precise than the FAOS and had similar responsiveness and test-retest reliability. The physical function and mobility CATs correlated strongly with the activities subscale of the FAOS, and the pain interference CAT correlated strongly with the pain subscale of the FAOS. The CATs and FAOS were responsive to changes with operative treatment for 6 common foot and ankle pathologies. The CATs performed as well as or better than the FAOS in all aspects of psychometric validity. The Patient-Reported Outcomes Measurement Information System CATs show tremendous potential for improving the study of patient outcomes in foot and ankle research through improved precision and reduced respondent burden. Level II, prospective comparative study.

Body Esteem as a Common Factor of a Tendency Toward Binge Eating and Sexual Dissatisfaction Among Women: The Role of Dissociation and Stress Response During Sex.

PubMed

Castellini, Giovanni; Lo Sauro, Carolina; Ricca, Valdo; Rellini, Alessandra H

2017-08-01

Several studies have suggested a relevant overlap between eating disorders and sexual dysfunction involving the emotional component of body image esteem and dissociative experiences. To evaluate the common maintaining factors of sexual dysfunction and vulnerability to pathologic eating behaviors and their relation to a physiologic stress response. In the present cross-sectional study, we evaluated a non-clinical sample of 60 heterosexual women (25-35 years old) for dissociation during sex with a partner, body image disturbance, and tendency toward pathologic eating behaviors. We also evaluated the stress-induced hypothalamic-pituitary-adrenal axis activation in response to a sexual stimulus and its association with binge eating and dissociation. Participants completed the Clinician-Administered Dissociative States Scale, the Sexual Satisfaction Scale-Women, the Body Esteem Scale for Adolescents and Adults, and the Eating Attitudes Test Short Version. Furthermore, we assessed cortisol levels before, during, and after exposure to explicit sexual stimuli shown within a laboratory setting. Dysfunctional body image esteem and a tendency toward binge-eating behaviors were associated with greater sexual distress in women. In particular, body esteem was significantly associated with greater dissociation during sex with a partner. Moreover, women who reported greater dissociation during sex with a partner and a tendency toward binge-eating behaviors showed higher levels of cortisol in response to sexual stimuli. These results support further research based on trans-diagnostic treatments targeted to dissociation and body image esteem, which could lessen sexual dysfunction and vulnerability to pathologic eating behaviors. Despite the small sample and self-reported questionnaires, this is the first study to consider the association of the stress response during sexual stimuli with sexual distress and with pathologic eating behaviors adopting a dimensional approach. Body uneasiness and dissociation represented factors underlying pathologic eating behaviors and sexual dysfunction. Women reporting a tendency toward binge-eating episodes and dissociation during sexual experiences represented a subpopulation with a higher stress response during sexual stimuli. Castellini G, Lo Sauro C, Ricca V, Rellini AH. Body Esteem as a Common Factor of a Tendency Toward Binge Eating and Sexual Dissatisfaction Among Women: The Role of Dissociation and Stress Response During Sex. J Sex Med 2017;14:1036-1045. Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Pathology during acute infections: contributions of intracellular pathogens and the CTL response.

PubMed

Ganusov, Vitaly V; Antia, Rustom

2005-06-22

Previous work has shown how, in the case of cytotoxic T-lymphocyte (CTL) responses to persistent viral infections, pathology may arise as a consequence of cell destruction directly by the virus or indirectly due to the CTL response, leading to maximum pathology at intermediate efficacy of the immune response. We expand these studies to consider pathology arising during acute infections with intracellular pathogens controlled by the CTL response. We show that, in contrast to persistent infections, pathology during acute infections is minimized with increasing efficacy of the immune response. The implications of these results for vaccination are discussed.

Digital pathology access and usage in the UK: results from a national survey on behalf of the National Cancer Research Institute's CM-Path initiative.

PubMed

Williams, Bethany Jill; Lee, Jessica; Oien, Karin A; Treanor, Darren

2018-05-01

To canvass the UK pathology community to ascertain current levels of digital pathology usage in clinical and academic histopathology departments, and prevalent attitudes to digital pathology. A 15-item survey was circulated to National Health Service and academic pathology departments across the UK using the SurveyMonkey online survey tool. Responses were sought at a departmental or institutional level. Where possible, departmental heads were approached and asked to complete the survey, or forward it to the most relevant individual in their department. Data were collected over a 6-month period from February to July 2017. 41 institutes from across the UK responded to the survey. 60% (23/39) of institutions had access to a digital pathology scanner, and 60% (24/40) had access to a digital pathology workstation. The most popular applications of digital pathology in current use were undergraduate and postgraduate teaching, research and quality assurance. Investigating the deployment of digital pathology in their department was identified as a high or highest priority by 58.5% of institutions, with improvements in efficiency, turnaround times, reporting times and collaboration in their institution anticipated by the respondents. Access to funding for initial hardware, software and staff outlay, pathologist training and guidance from the Royal College of Pathologists were identified as factors that could enable respondent institutions to increase their digital pathology usage. Interest in digital pathology adoption in the UK is high, with usage likely to increase in the coming years. In light of this, pathologists are seeking more guidance on safe usage. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Digital pathology access and usage in the UK: results from a national survey on behalf of the National Cancer Research Institute’s CM-Path initiative

PubMed Central

Williams, Bethany Jill; Lee, Jessica; Oien, Karin A; Treanor, Darren

2018-01-01

Aim To canvass the UK pathology community to ascertain current levels of digital pathology usage in clinical and academic histopathology departments, and prevalent attitudes to digital pathology. Methods A 15-item survey was circulated to National Health Service and academic pathology departments across the UK using the SurveyMonkey online survey tool. Responses were sought at a departmental or institutional level. Where possible, departmental heads were approached and asked to complete the survey, or forward it to the most relevant individual in their department. Data were collected over a 6-month period from February to July 2017. Results 41 institutes from across the UK responded to the survey. 60% (23/39) of institutions had access to a digital pathology scanner, and 60% (24/40) had access to a digital pathology workstation. The most popular applications of digital pathology in current use were undergraduate and postgraduate teaching, research and quality assurance. Investigating the deployment of digital pathology in their department was identified as a high or highest priority by 58.5% of institutions, with improvements in efficiency, turnaround times, reporting times and collaboration in their institution anticipated by the respondents. Access to funding for initial hardware, software and staff outlay, pathologist training and guidance from the Royal College of Pathologists were identified as factors that could enable respondent institutions to increase their digital pathology usage. Conclusion Interest in digital pathology adoption in the UK is high, with usage likely to increase in the coming years. In light of this, pathologists are seeking more guidance on safe usage. PMID:29317516

Dose-Effect Relationship in Chemoradiotherapy for Locally Advanced Rectal Cancer: A Randomized Trial Comparing Two Radiation Doses

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

Jakobsen, Anders, E-mail: anders.jakobsen@slb.regionsyddanmark.dk; University of Southern Denmark, Odense; Ploen, John

2012-11-15

Purpose: Locally advanced rectal cancer represents a major therapeutic challenge. Preoperative chemoradiation therapy is considered standard, but little is known about the dose-effect relationship. The present study represents a dose-escalation phase III trial comparing 2 doses of radiation. Methods and Materials: The inclusion criteria were resectable T3 and T4 tumors with a circumferential margin of {<=}5 mm on magnetic resonance imaging. The patients were randomized to receive 50.4 Gy in 28 fractions to the tumor and pelvic lymph nodes (arm A) or the same treatment supplemented with an endorectal boost given as high-dose-rate brachytherapy (10 Gy in 2 fractions; armmore » B). Concomitant chemotherapy, uftoral 300 mg/m{sup 2} and L-leucovorin 22.5 mg/d, was added to both arms on treatment days. The primary endpoint was complete pathologic remission. The secondary endpoints included tumor response and rate of complete resection (R0). Results: The study included 248 patients. No significant difference was found in toxicity or surgical complications between the 2 groups. Based on intention to treat, no significant difference was found in the complete pathologic remission rate between the 2 arms (18% and 18%). The rate of R0 resection was different in T3 tumors (90% and 99%; P=.03). The same applied to the rate of major response (tumor regression grade, 1+2), 29% and 44%, respectively (P=.04). Conclusions: This first randomized trial comparing 2 radiation doses indicated that the higher dose increased the rate of major response by 50% in T3 tumors. The endorectal boost is feasible, with no significant increase in toxicity or surgical complications.« less

Efficacy and Safety of Low-Dose-Rate Endorectal Brachytherapy as a Boost to Neoadjuvant Chemoradiation in the Treatment of Locally Advanced Distal Rectal Cancer: A Phase-II Clinical Trial

PubMed Central

Omidvari, Shapour; Zohourinia, Shadi; Ansari, Mansour; Ghahramani, Leila; Zare-Bandamiri, Mohammad; Mosalaei, Ahmad; Ahmadloo, Niloofar; Pourahmad, Saeedeh; Nasrolahi, Hamid; Hamedi, Sayed Hasan

2015-01-01

Purpose Despite advances in rectal cancer treatment over the last decade, local control and risk of late side effects due to external beam radiation therapy (EBRT) remain as concerns. The present study aimed to investigate the efficacy and the safety of low-dose-rate endorectal brachytherapy (LDRBT) as a boost to neoadjuvant chemoradiation for use in treating locally advanced distal rectal adenocarcinomas. Methods This phase-II clinical trial included 34 patients (as the study arm) with newly diagnosed, locally advanced (clinical T3-T4 and/or N1/N2, M0) lower rectal cancer. For comparative analysis, 102 matched patients (as the historical control arm) with rectal cancer were also selected. All the patients were treated with LDRBT (15 Gy in 3 fractions) and concurrent chemoradiation (45-50.4 Gy). Concurrent chemotherapy consisted of oxaliplatin 130 mg/m2 intravenously on day 1 plus oral capecitabine 825 mg/m2 twice daily during LDRBT and EBRT. Results The study results revealed a significant differences between the study arm and the control arm in terms in the pathologic tumor size (2.1 cm vs. 3.6 cm, P = 0.001), the pathologic tumor stage (35% T3-4 vs. 65% T3-4, P = 0.003), and the pathologic complete response (29.4% vs. 11.7%, P < 0.028). Moreover, a significantly higher dose of EBRT (P = 0.041) was found in the control arm, and a longer time to surgery was observed in the study arm (P < 0.001). The higher rate of treatment-related toxicities, such as mild proctitis and anemia, in the study arm was tolerable and easily manageable. Conclusion A boost of LDRBT can optimize the pathologic complete response, with acceptable toxicities, in patients with distal rectal cancer. PMID:26361613

Efficacy and Safety of Low-Dose-Rate Endorectal Brachytherapy as a Boost to Neoadjuvant Chemoradiation in the Treatment of Locally Advanced Distal Rectal Cancer: A Phase-II Clinical Trial.

PubMed

Omidvari, Shapour; Zohourinia, Shadi; Ansari, Mansour; Ghahramani, Leila; Zare-Bandamiri, Mohammad; Mosalaei, Ahmad; Ahmadloo, Niloofar; Pourahmad, Saeedeh; Nasrolahi, Hamid; Hamedi, Sayed Hasan; Mohammadianpanah, Mohammad

2015-08-01

Despite advances in rectal cancer treatment over the last decade, local control and risk of late side effects due to external beam radiation therapy (EBRT) remain as concerns. The present study aimed to investigate the efficacy and the safety of low-dose-rate endorectal brachytherapy (LDRBT) as a boost to neoadjuvant chemoradiation for use in treating locally advanced distal rectal adenocarcinomas. This phase-II clinical trial included 34 patients (as the study arm) with newly diagnosed, locally advanced (clinical T3-T4 and/or N1/N2, M0) lower rectal cancer. For comparative analysis, 102 matched patients (as the historical control arm) with rectal cancer were also selected. All the patients were treated with LDRBT (15 Gy in 3 fractions) and concurrent chemoradiation (45-50.4 Gy). Concurrent chemotherapy consisted of oxaliplatin 130 mg/m(2) intravenously on day 1 plus oral capecitabine 825 mg/m(2) twice daily during LDRBT and EBRT. The study results revealed a significant differences between the study arm and the control arm in terms in the pathologic tumor size (2.1 cm vs. 3.6 cm, P = 0.001), the pathologic tumor stage (35% T3-4 vs. 65% T3-4, P = 0.003), and the pathologic complete response (29.4% vs. 11.7%, P < 0.028). Moreover, a significantly higher dose of EBRT (P = 0.041) was found in the control arm, and a longer time to surgery was observed in the study arm (P < 0.001). The higher rate of treatment-related toxicities, such as mild proctitis and anemia, in the study arm was tolerable and easily manageable. A boost of LDRBT can optimize the pathologic complete response, with acceptable toxicities, in patients with distal rectal cancer.

Assessment of thought-shape fusion: initial validation of a short version of the trait thought-shape fusion scale.

PubMed

Coelho, Jennifer S; Baeyens, Céline; Purdon, Christine; Shafran, Roz; Roulin, Jean-Luc; Bouvard, Martine

2013-01-01

Thought-shape fusion (TSF) is a cognitive distortion that has been linked to eating pathology. Two studies were conducted to further explore this phenomenon and to establish the psychometric properties of a French short version of the TSF scale. In Study 1, students (n = 284) completed questionnaires assessing TSF and related psychopathology. In Study 2, the responses of women with eating disorders (n = 22) and women with no history of an eating disorder (n = 23) were compared. The French short version of the TSF scale has a unifactorial structure, with convergent validity with measures of eating pathology, and good internal consistency. Depression, eating pathology, body dissatisfaction, and thought-action fusion emerged as predictors of TSF. Individuals with eating disorders have higher TSF, and more clinically relevant food-related thoughts than do women with no history of an eating disorder. This research suggests that the shortened TSF scale can suitably measure this construct, and provides support for the notion that TSF is associated with eating pathology. Copyright © 2012 Wiley Periodicals, Inc.

Prospective study of neoadjuvant chemoradiotherapy using intensity-modulated radiotherapy and 5 fluorouracil for locally advanced rectal cancer - toxicities and response assessment.

PubMed

Simson, David K; Mitra, Swarupa; Ahlawat, Parveen; Saxena, Upasna; Sharma, Manoj Kumar; Rawat, Sheh; Singh, Harpreet; Bansal, Babita; Sripathi, Lalitha Kameshwari; Tanwar, Aditi

2018-01-01

The past 2 decades witnessed the strengthening of evidence favoring the role of neoadjuvant chemoradiation (CHRT) in the treatment of locally advanced rectal cancer. The study aims to evaluate the response and acute toxicities to neoadjuvant CHRT using intensity-modulated radiotherapy (IMRT) in the treatment of rectal cancer. Predictive factors to achieve pathological complete response (pCR) were analyzed, as a secondary endpoint. All consecutive patients who underwent IMRT as part of neoadjuvant CHRT in the treatment of rectal cancer between August 2014 and December 2016 at a tertiary cancer care center were accrued for the study. The cohort underwent CHRT with IMRT technique at a dose of 50.4 Gy in 28 fractions concurrent with continuous infusion of 5 fluorouracil during the first and the last 4 days of CHRT. Surgery was performed 6 weeks later and the pathological response to CHRT was noted. Forty-three subjects were accrued for the study. Radiation dermatitis and diarrhea were the only observed grade ≥3 acute toxicities. Sphincter preservation rate (SPR) was 43.3%. pCR was observed in 32.6%. Univariate and multivariate logistic regression showed that carcinoembryonic antigen was the only independent predictive factor to achieve pCR. IMRT as part of neoadjuvant CHRT in the treatment of locally advanced rectal cancer is well tolerated and gives comparable results with respect to earlier studies in terms of pathological response and SPR. Further randomized controlled studies are needed to firmly state that IMRT is superior to 3-dimensional conformal radiotherapy.

T-cell-dependent immunity and thrombocytopenia in rats infected with Plasmodium chabaudi.

PubMed Central

Watier, H; Verwaerde, C; Landau, I; Werner, E; Fontaine, J; Capron, A; Auriault, C

1992-01-01

Normal, splenectomized, and athymic Fischer rats were infected with Plasmodium chabaudi. In normal rat infections, acute-phase infection resolved rapidly and completely. In splenectomized rats, infection resulted in high parasitemia and ultimately death. In nude rats, parasite growth was reduced compared with normal rats, and a persistent parasitemia (between 20 and 45%) was observed for several months. Complete resolution of the infection was achieved after adoptive transfer of T lymphocytes, even when transfer occurred during the course of infection. These results indicated that an acquired, T-lymphocyte-dependent immunity was necessary for the complete recovery observed in normal rats. In normal rats, thrombocytopenia and splenomegaly occurred during infection. By contrast, in nude rats, both of these pathological manifestations were only observed after thymus grafting. Thrombocytopenia was also absent in the splenectomized animals. Despite an increase in platelet-associated immunoglobulin levels during the infection, thrombocytopenia was not transferred by injection of infected rat serum to normal recipients. It has been concluded that the nude rat infection can be regarded as a novel and useful model for studying the T-cell-dependent effector and pathological mechanisms and to investigate the anti-P. chabaudi immune response. PMID:1729178

Early FDG PET response assessment of preoperative radiochemotherapy in locally advanced rectal cancer: correlation with long-term outcome.

PubMed

Avallone, Antonio; Aloj, Luigi; Caracò, Corradina; Delrio, Paolo; Pecori, Biagio; Tatangelo, Fabiana; Scott, Nigel; Casaretti, Rossana; Di Gennaro, Francesca; Montano, Massimo; Silvestro, Lucrezia; Budillon, Alfredo; Lastoria, Secondo

2012-12-01

The aim of the present study is to prospectively evaluate the prognostic value of previously defined [(18)F]2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) criteria of early metabolic response in patients with locally advanced rectal cancer (LARC) after long-term follow-up. Forty-two patients with poor prognosis LARC underwent three biweekly courses of chemotherapy with oxaliplatin, raltitrexed and 5-fluorouracil modulated by levofolinic acid during pelvic radiotherapy. FDG PET studies were performed before and 12 days after the beginning of the chemoradiotherapy (CRT) treatment. Total mesorectal excision (TME) was carried out 8 weeks after completion of CRT. A previously identified cutoff value of ≥52 % reduction of the baseline mean FDG standardized uptake value (SUV(mean)) was applied to differentiate metabolic responders from non-responders and correlated to tumour regression grade (TRG) and survival. Twenty-two metabolic responders showed complete (TRG1) or subtotal tumour regression (TRG2) and demonstrated a statistically significantly higher 5-year relapse-free survival (RFS) compared with the 20 non-responders (86 vs 55 %, p = .014) who showed TRG3 and TRG4 pathologic responses. A multivariate analysis demonstrated that early ∆SUV(mean) was the only pre-surgical parameter correlated to the likelihood of recurrence (p = .05). This study is the first prospective long-term evaluation demonstrating that FDG PET is not only an early predictor of pathologic response but is also a valuable prognostic tool. Our results indicate the potential of FDG PET for optimizing multidisciplinary management of patients with LARC.

Response monitoring of breast cancer patients receiving neoadjuvant chemotherapy using quantitative ultrasound, texture, and molecular features

PubMed Central

Gangeh, Mehrdad; Tadayyon, Hadi; Sadeghi-Naini, Ali; Gandhi, Sonal; Wright, Frances C.; Slodkowska, Elzbieta; Curpen, Belinda; Tran, William; Czarnota, Gregory J.

2018-01-01

Background Pathological response of breast cancer to chemotherapy is a prognostic indicator for long-term disease free and overall survival. Responses of locally advanced breast cancer in the neoadjuvant chemotherapy (NAC) settings are often variable, and the prediction of response is imperfect. The purpose of this study was to detect primary tumor responses early after the start of neoadjuvant chemotherapy using quantitative ultrasound (QUS), textural analysis and molecular features in patients with locally advanced breast cancer. Methods The study included ninety six patients treated with neoadjuvant chemotherapy. Breast tumors were scanned with a clinical ultrasound system prior to chemotherapy treatment, during the first, fourth and eighth week of treatment, and prior to surgery. Quantitative ultrasound parameters and scatterer-based features were calculated from ultrasound radio frequency (RF) data within tumor regions of interest. Additionally, texture features were extracted from QUS parametric maps. Prior to therapy, all patients underwent a core needle biopsy and histological subtypes and biomarker ER, PR, and HER2 status were determined. Patients were classified into three treatment response groups based on combination of clinical and pathological analyses: complete responders (CR), partial responders (PR), and non-responders (NR). Response classifications from QUS parameters, receptors status and pathological were compared. Discriminant analysis was performed on extracted parameters using a support vector machine classifier to categorize subjects into CR, PR, and NR groups at all scan times. Results Of the 96 patients, the number of CR, PR and NR patients were 21, 52, and 23, respectively. The best prediction of treatment response was achieved with the combination mean QUS values, texture and molecular features with accuracies of 78%, 86% and 83% at weeks 1, 4, and 8, after treatment respectively. Mean QUS parameters or clinical receptors status alone predicted the three response groups with accuracies less than 60% at all scan time points. Recurrence free survival (RFS) of response groups determined based on combined features followed similar trend as determined based on clinical and pathology. Conclusions This work demonstrates the potential of using QUS, texture and molecular features for predicting the response of primary breast tumors to chemotherapy early, and guiding the treatment planning of refractory patients. PMID:29298305

[A case report of anorectal malignant melanoma showing a complete response after DTIC/ACNU/VCR therapy].

PubMed

Sasaki, Shin; Kojima, Tetsu; Hidemura, Akio; Hatanaka, Kazuhito; Uekusa, Toshimasa; Ishimaru, Masahiro

2010-10-01

We report herein the case of a 64-year-old male who presented with hematochezia. The patient was diagnosed with malignant melanoma of the anorectum using colonoscopy. Preoperative studies revealed no distant metastases, and he underwent Miles operation. Pathological exams revealed that the tumor had invaded the submucosa with lymphatic and venous invasion. Cancer cells were found in regional lymph nodes. Post-operative CT scan demonstrated multiple metastases in the liver, and he received two courses of combined chemotherapy, DAV regimen (dacarbazine: DTIC 100 mg iv days 1-5, nimustine hydrochloride: ACNU 100 mg iv day 1, vincristine sulfate: VCR 1 mg iv day 1), leading to a complete response. However, malignant melanoma cells were found in hernia contents at the operation for left inguinal hernia, which led to a diagnosis of recurrent malignant melanoma. The patient has subsequently been well without any sign of recurrence including liver metastases. To our knowledge, this is the first report of a complete response in a patient with multiple liver metastases of anorectal malignant melanoma after DAV regimen.

Tumor response ratio predicts overall survival in breast cancer patients treated with neoadjuvant chemotherapy.

PubMed

Miller, Marian; Ottesen, Rebecca A; Niland, Joyce C; Kruper, Laura; Chen, Steven L; Vito, Courtney

2014-10-01

Neoadjuvant chemotherapy (NAC) is commonly used to treat locally advanced breast cancer. Pathologic complete response (pCR) predicts improved overall survival (OS); however, prognosis of patients with partial response remains unclear. We evaluated whether tumor response ratio (TRR) is a better predictor of OS than current staging methods. Using the National Comprehensive Cancer Network Breast Cancer Outcomes Database, we identified patients with stage I-III breast cancer who had NAC and pretreatment imaging at City of Hope (1997-2010). Patient demographics, tumor characteristics, and OS were analyzed. TRR was calculated as residual in-breast disease divided by size on pre-NAC imaging. Four TRR groups were stratified; TRR 0 (pCR), TRR > 0-0.4 (strong partial response, SPR), TRR > 0.4-1.0 (weak partial response, WPR), or TRR > 1.0 (tumor growth, TG). OS was estimated by the Kaplan-Meier method and tested by the log-rank test. Cox regression was performed to evaluate associations between OS and TRR in a multivariable analysis while controlling for potential confounders. There were 218 eligible patients identified; 59 (27 %) had pCR, 61 (28 %) SPR, 72 (33 %) WPR, and 26 (12 %) TG. Five-year OS decreased continuously with increasing TRR:pCR (90 %), SPR (79 %), WPR (66 %), and TG (60 %). TRR was the only measure that significantly predicted OS (p = 0.0035); pathologic stage (p = 0.23) and pre-NAC clinical tumor stage (cT) (p = 0.87) were not significant. TRR continued to be statistically significant by multivariable analysis (p = 0.016). TRR takes into account both pretreatment and residual disease and more accurately predicts OS than pathologic stage and pre-NAC cT. TRR may be useful to more accurately assess prognosis and OS in breast cancer patients undergoing NAC.

Predicting neo-adjuvant chemotherapy response and progression-free survival of locally advanced breast cancer using textural features of intratumoral heterogeneity on F-18 FDG PET/CT and diffusion-weighted MR imaging.

PubMed

Yoon, Hai-Jeon; Kim, Yemi; Chung, Jin; Kim, Bom Sahn

2018-03-30

Predicting response to neo-adjuvant chemotherapy (NAC) and survival in locally advanced breast cancer (LABC) is important. This study investigated the prognostic value of tumor heterogeneity evaluated with textural analysis through F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) and diffusion-weighted imaging (DWI). We enrolled 83 patients with LABC who had completed NAC and curative surgery. Tumor texture indices from pretreatment FDG PET and DWI were extracted from histogram analysis and 7 different parent matrices: co-occurrence matrix, the voxel-alignment matrix, neighborhood intensity difference matrix, intensity size-zone matrix (ISZM), normalized gray-level co-occurrence matrix (NGLCM), neighboring gray-level dependence matrix (NGLDM), and texture spectrum matrix. The predictive values of textural features were tested regarding both pathologic NAC response and progression-free survival. Among 83 patients, 46 were pathologic responders, while 37 were nonresponders. The PET texture indices from 7 parent matrices, DWI texture indices from histogram, and 1 parent matrix (NGLCM) showed significant differences according to NAC response. On multivariable analysis, number nonuniformity of PET extracted from the NGLDM was an independent predictor of pathologic response (P = .009). During a median follow-up period of 17.3 months, 14 patients experienced recurrence. High-intensity zone emphasis (HIZE) and high-intensity short-zone emphasis (HISZE) from PET extracted from ISZM were significant textural predictors (P = .011 and P = .033). On Cox regression analysis, only HIZE was a significant predictor of recurrence (P = .027), while HISZE showed borderline significance (P = .107). Tumor texture indices are useful for NAC response prediction in LABC. Moreover, PET texture indices can help to predict disease recurrence. © 2018 Wiley Periodicals, Inc.

Data Set for Pathology Reporting of Cutaneous Invasive Melanoma

PubMed Central

Judge, Meagan J.; Evans, Alan; Frishberg, David P.; Prieto, Victor G.; Thompson, John F.; Trotter, Martin J.; Walsh, Maureen Y.; Walsh, Noreen M.G.; Ellis, David W.

2013-01-01

An accurate and complete pathology report is critical for the optimal management of cutaneous melanoma patients. Protocols for the pathologic reporting of melanoma have been independently developed by the Royal College of Pathologists of Australasia (RCPA), Royal College of Pathologists (United Kingdom) (RCPath), and College of American Pathologists (CAP). In this study, data sets, checklists, and structured reporting protocols for pathologic examination and reporting of cutaneous melanoma were analyzed by an international panel of melanoma pathologists and clinicians with the aim of developing a common, internationally agreed upon, evidence-based data set. The International Collaboration on Cancer Reporting cutaneous melanoma expert review panel analyzed the existing RCPA, RCPath, and CAP data sets to develop a protocol containing “required” (mandatory/core) and “recommended” (nonmandatory/noncore) elements. Required elements were defined as those that had agreed evidentiary support at National Health and Medical Research Council level III-2 level of evidence or above and that were unanimously agreed upon by the review panel to be essential for the clinical management, staging, or assessment of the prognosis of melanoma or fundamental for pathologic diagnosis. Recommended elements were those considered to be clinically important and recommended for good practice but with lesser degrees of supportive evidence. Sixteen core/required data elements for cutaneous melanoma pathology reports were defined (with an additional 4 core/required elements for specimens received with lymph nodes). Eighteen additional data elements with a lesser level of evidentiary support were included in the recommended data set. Consensus response values (permitted responses) were formulated for each data item. Development and agreement of this evidence-based protocol at an international level was accomplished in a timely and efficient manner, and the processes described herein may facilitate the development of protocols for other tumor types. Widespread utilization of an internationally agreed upon, structured pathology data set for melanoma will lead not only to improved patient management but is a prerequisite for research and for international benchmarking in health care. PMID:24061524

RNA-based determination of ESR1 and HER2 expression and response to neoadjuvant chemotherapy.

PubMed

Denkert, C; Loibl, S; Kronenwett, R; Budczies, J; von Törne, C; Nekljudova, V; Darb-Esfahani, S; Solbach, C; Sinn, B V; Petry, C; Müller, B M; Hilfrich, J; Altmann, G; Staebler, A; Roth, C; Ataseven, B; Kirchner, T; Dietel, M; Untch, M; von Minckwitz, G

2013-03-01

Hormone and human epidermal growth factor receptor 2 (HER2) receptors are the most important breast cancer biomarkers, and additional objective and quantitative test methods such as messenger RNA (mRNA)-based quantitative analysis are urgently needed. In this study, we investigated the clinical validity of RT-PCR-based evaluation of estrogen receptor (ESR1) and HER2 mRNA expression. A total of 1050 core biopsies from two retrospective (GeparTrio, GeparQuattro) and one prospective (PREDICT) neoadjuvant studies were evaluated by quantitative RT-PCR for ESR1 and HER2. ESR1 mRNA was significantly predictive for reduced response to neoadjuvant chemotherapy in univariate and multivariate analysis in all three cohorts. The complete pathologically documented response (pathological complete response, pCR) rate for ESR1+/HER2- tumors was 7.3%, 8.0% and 8.6%; for ESR1-/HER2- tumors it was 34.4%, 33.7% and 37.3% in GeparTrio, GeparQuattro and PREDICT, respectively (P < 0.001 in each cohort). In the Kaplan-Meier analysis in GeparTrio patients with ESR1+/HER2- tumors had the best prognosis, compared with ESR1-/HER2- and ESR1-/HER2+ tumors [disease-free survival (DFS): P < 0.0005, overall survival (OS): P < 0.0005]. Our results suggest that mRNA levels of ESR1 and HER2 predict response to neoadjuvant chemotherapy and are significantly associated with long-term outcome. As an additional option to standard immunohistochemistry and gene-array-based analysis, quantitative RT-PCR analysis might be useful for determination of the receptor status in breast cancer.

Increased pathological complete response rate after a long-term neoadjuvant letrozole treatment in postmenopausal oestrogen and/or progesterone receptor-positive breast cancer

PubMed Central

Allevi, G; Strina, C; Andreis, D; Zanoni, V; Bazzola, L; Bonardi, S; Foroni, C; Milani, M; Cappelletti, M R; Gussago, F; Aguggini, S; Giardini, R; Martinotti, M; Fox, S B; Harris, A L; Bottini, A; Berruti, A; Generali, D

2013-01-01

Background: The objective of this study was to determine the optimal scheduling of 2.5 mg daily letrozole in neoadjuvant breast cancer patients to obtain pathological complete response (pathCR) and assess Ki-67 expression as an early predictor of response. Patients and methods: This single institution study comprised 120 oestrogen receptor (ER)-positive postmenopausal women with primary breast cancer (clinical stage ⩾T2, N0–1), from three sequential cohorts (cohort A of 40, cohort B of 40 and cohort C of 40 patients, respectively) based on different duration of the neoadjuvant letrozole. Biological markers such as ER, progesterone receptor, HER2 and Ki-67 expression were tested at diagnosis and at definitive surgery. Results: A total of 89 patients (75.4%) achieved an objective response with 44 (37.3%) clinical CRs and 45 (38.1%) partial responses. The clinical CRs were significantly observed in cohort C (23 out of 40 patients, 57.5%) and B (16 out of 38 patients, 42.1%) compared with cohort A (5 out of 40 patients, 12.5%) (P-value for trend <0.001). Letrozole induced a similar significant reduction in Ki-67 index after treatment in all cohorts. The pathCR rate was significantly more frequent in cohort C (7 out of 40 patients, 17.5%) than in cohort A (1 out of 40 patients, 2.5%) and B (2 out of 40 patients, 5.0%) (P-value for trend <0.04). Conclusion: One-year neoadjuvant letrozole therapy leads to a higher pathCR rate and may be the optimal length of drug exposure. PMID:23579222

Reversing pathological neural activity using targeted plasticity.

PubMed

Engineer, Navzer D; Riley, Jonathan R; Seale, Jonathan D; Vrana, Will A; Shetake, Jai A; Sudanagunta, Sindhu P; Borland, Michael S; Kilgard, Michael P

2011-02-03

Brain changes in response to nerve damage or cochlear trauma can generate pathological neural activity that is believed to be responsible for many types of chronic pain and tinnitus. Several studies have reported that the severity of chronic pain and tinnitus is correlated with the degree of map reorganization in somatosensory and auditory cortex, respectively. Direct electrical or transcranial magnetic stimulation of sensory cortex can temporarily disrupt these phantom sensations. However, there is as yet no direct evidence for a causal role of plasticity in the generation of pain or tinnitus. Here we report evidence that reversing the brain changes responsible can eliminate the perceptual impairment in an animal model of noise-induced tinnitus. Exposure to intense noise degrades the frequency tuning of auditory cortex neurons and increases cortical synchronization. Repeatedly pairing tones with brief pulses of vagus nerve stimulation completely eliminated the physiological and behavioural correlates of tinnitus in noise-exposed rats. These improvements persisted for weeks after the end of therapy. This method for restoring neural activity to normal may be applicable to a variety of neurological disorders.

Reversing pathological neural activity using targeted plasticity

PubMed Central

Engineer, Navzer D.; Riley, Jonathan R.; Seale, Jonathan D.; Vrana, Will A.; Shetake, Jai A.; Sudanagunta, Sindhu P.; Borland, Michael S.; Kilgard, Michael P.

2012-01-01

Brain changes in response to nerve damage or cochlear trauma can generate pathological neural activity that is believed to be responsible for many types of chronic pain and tinnitus1–3. Several studies have reported that the severity of chronic pain and tinnitus is correlated with the degree of map reorganization in somatosensory and auditory cortex, respectively1,4. Direct electrical or transcranial magnetic stimulation of sensory cortex can temporarily disrupt these phantom sensations5. However, there is as yet no direct evidence for a causal role of plasticity in the generation of pain or tinnitus. Here we report evidence that reversing the brain changes responsible can eliminate the perceptual impairment in an animal model of noise-induced tinnitus. Exposure to intense noise degrades the frequency tuning of auditory cortex neurons and increases cortical synchronization. Repeatedly pairing tones with brief pulses of vagus nerve stimulation completely eliminated the physiological and behavioural correlates of tinnitus in noise-exposed rats. These improvements persisted for weeks after the end of therapy. This method for restoring neural activity to normal may be applicable to a variety of neurological disorders. PMID:21228773

CBT for eating disorders: The impact of early changes in eating pathology on later changes in personality pathology, anxiety and depression.

PubMed

Turner, Hannah; Marshall, Emily; Wood, Francesca; Stopa, Lusia; Waller, Glenn

2016-02-01

Whilst studies have consistently identified early symptom reduction as an important predictor of treatment outcome, the impact of early change on common comorbid features has not been investigated. This study of CBT for eating disorders explored patterns of early change in eating pathology and longer-term change in personality pathology, anxiety and depression. It also explored the impact of early change in eating pathology on overall change in personality pathology, anxiety and depression. Participants were 179 adults diagnosed with eating disorders who were offered a course of CBT in an out-patient community eating disorders service in the UK. Patients completed a measure of eating disorder psychopathology at the start of treatment and following the 6th session. They also completed measures of personality disorder cognitions, anxiety and depression at the start and end of treatment. There were significant changes in eating pathology over the first six sessions of treatment. Significant improvements were also seen in personality disorder pathology, anxiety and depression by the end of therapy. Effect sizes were medium to large for both completer and intention to treat analyses. Early changes in eating pathology were associated with later changes in common comorbid features, with early reduction in restraint being a key predictor. These findings demonstrate that early symptom change can be achieved in CBT for eating disorders when delivered in routine clinical practice. Such change has long-term benefits that go beyond the domain of eating pathology, enhancing change in personality pathology, anxiety and depression. Copyright © 2015 Elsevier Ltd. All rights reserved.

Complex networks analysis of obstructive nephropathy data

NASA Astrophysics Data System (ADS)

Zanin, M.; Boccaletti, S.

2011-09-01

Congenital obstructive nephropathy (ON) is one of the most frequent and complex diseases affecting children, characterized by an abnormal flux of the urine, due to a partial or complete obstruction of the urinary tract; as a consequence, urine may accumulate in the kidney and disturb the normal operation of the organ. Despite important advances, pathological mechanisms are not yet fully understood. In this contribution, the topology of complex networks, based on vectors of features of control and ON subjects, is related with the severity of the pathology. Nodes in these networks represent genetic and metabolic profiles, while connections between them indicate an abnormal relation between their expressions. Resulting topologies allow discriminating ON subjects and detecting which genetic or metabolic elements are responsible for the malfunction.

Histologic Appearance After Preoperative Radiation Therapy for Soft Tissue Sarcoma: Assessment of the European Organization for Research and Treatment of Cancer–Soft Tissue and Bone Sarcoma Group Response Score

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

Schaefer, Inga-Marie; Hornick, Jason L.; Barysauskas, Constance M.

Purpose: To critically assess the prognostic value of the European Organization for Research and Treatment of Cancer–Soft Tissue and Bone Sarcoma Group (EORTC-STBSG) response score and define histologic appearance after preoperative radiation therapy (RT) for soft tissue sarcoma (STS). Methods and Materials: For a cohort of 100 patients with STS of the extremity/trunk treated at our institution with preoperative RT followed by resection, 2 expert sarcoma pathologists evaluated the resected specimens for percent residual viable cells, necrosis, hyalinization/fibrosis, and infarction. The EORTC response score and other predictors of recurrence-free survival (RFS) and overall survival (OS) were assessed by Kaplan-Meier and proportionalmore » hazard models. Results: Median tumor size was 7.5 cm; 92% were intermediate or high grade. Most common histologies were unclassified sarcoma (34%) and myxofibrosarcoma (25%). Median follow-up was 60 months. The 5-year local recurrence rate was 5%, 5-year RFS was 68%, and 5-year OS was 75%. Distribution of cases according to EORTC response score tiers was as follows: no residual viable tumor for 9 cases (9% pathologic complete response); <1% viable tumor for 0, ≥1% to <10% for 9, ≥10% to <50% for 44, and ≥50% for 38. There was no association between EORTC-STBSG response score and RFS or OS. Conversely, hyalinization/fibrosis was a significant independent favorable predictor for RFS (hazard ratio 0.49, P=.007) and OS (hazard ratio 0.36, P=.02). Conclusion: Histologic evaluation after preoperative RT for STS showed a 9% pathologic complete response rate. The EORTC-STBSG response score and percent viable cells were not prognostic. Hyalinization/fibrosis was associated with favorable outcome, and if validated, may become a valid endpoint for neoadjuvant trials.« less

Breast cancer sensitivity to neoadjuvant therapy in BRCA1 and CHEK2 mutation carriers and non-carriers.

PubMed

Pfeifer, Werner; Sokolenko, Anna P; Potapova, Olga N; Bessonov, Alexandr A; Ivantsov, Alexandr O; Laptiev, Sergey A; Zaitseva, Olga A; Yatsuk, Olga S; Matsko, Dmitry E; Semiglazova, Tatiana Yu; Togo, Alexandr V; Imyanitov, Evgeny N

2014-12-01

Breast carcinomas caused by inheritance of cancer-predisposing germ-line mutations have specific bioclinical features. This study aimed to analyze the efficacy of conventional cytotoxic treatment in BRCA1 and CHEK2 mutation carriers and non-carriers. The study included 415 Russian breast cancer patients aged 50 years or younger, who were subjected to various standard schemes of neoadjuvant therapy. The choice of therapy was done without the knowledge of the mutations status, because DNA testing was performed retrospectively using the archival tissue samples. 19 BRCA1 (4.6%) and 8 CHEK2 (1.9%) heterozygous genotypes were identified. BRCA1 mutation carriers achieved pathological complete response more frequently than non-carriers [6/19 (31.6%) vs. 46/388 (11.9%), p = 0.024]; this effect was limited to women treated by anthracycline-based therapy without taxanes [5/9 (55.6%) vs. 28/247 (11.3%), p = 0.002] and was not observed in any of 7 BRCA1 carriers receiving taxane-containing regimens. CHEK2 heterozygotes did not experience pathological complete response and showed lower frequency of objective clinical responses as compared to mutation non-carriers [4/8 (50%) vs. 333/388 (85.5%), p = 0.020]; the efficacy of neoadjuvant therapy was particularly poor in CHEK2 carriers receiving anthracyclines without taxanes. This study provides evidence for distinct sensitivity of BRCA1 and CHEK2 mutation-driven breast carcinomas to standard chemotherapeutic schemes.

Could less be more when assessing patient-rated outcome in spinal stenosis?

PubMed

Mannion, Anne F; Fekete, Tamas F; Wertli, Maria M; Mattle, Michele; Nauer, Selina; Kleinstück, Frank S; Jeszenszky, Dezsö; Haschtmann, Daniel; Becker, Hans-Jürgen; Porchet, François

2015-05-15

Longitudinal study of the measurement properties of a brief outcome instrument. In patients undergoing surgery for lumbar spinal stenosis, we compared the responsiveness of the Core Outcome Measures Index (COMI) with that of the condition-specific Swiss Spinal Stenosis Measure (SSM), an instrument developed to assess patients with neurogenic claudication. The COMI is a validated multidimensional questionnaire for assessing the key outcomes of importance to patients with back problems. Being brief, it is associated with minimal respondent burden and high completion rates. However, for a given pathology, intuitively it may be expected to be less responsive than a condition-specific instrument. A total of 91 patients (73±8 yr; 53% males) completed the following questionnaires before surgery: COMI, SSM, Roland Morris Disability Questionnaire, back trouble "Feeling Thermometer," pain numeric rating scale, EuroQoL-visual analogue scale. Twelve months postoperatively, 78/91 (86%) completed all the questionnaires again; they also rated the "global treatment outcome" (GTO; rated 1-5) and SSM "satisfaction with treatment result" (SSM-sat; rated 1-4), which were used as external criteria of treatment success. Scores for the external criteria of success (GTO/SSM-sat) correlated with the change scores (baseline to 12 mo) in COMI (r=0.57) and SSM (r=0.54) to a similar extent. Using receiver operating characteristics, with GTO or SSM-sat dichotomized as external criterion, the area under the curve was similar for the COMI change score (0.86-0.90) and the SSM (sub)scales (0.80-0.90). With either SSM-sat or GTO serving as the external criterion, COMI was as responsive as the SSM. The COMI is well able to detect important change in lumbar spinal stenosis and has the added benefit of reducing the response burden for the patient and facilitating outcome comparisons with other spinal pathologies. 2.

[Axillary pathologic response after neoadjuvant chemotherapy in locally advanced breast cancer with axillary involvement].

PubMed

Jiménez-Ballvé, A; Serrano-Palacio, A; García-Sáenz, J A; Ortega Candil, A; Salsidua-Arroyo, O; Román-Santamaría, J M; Pelayo Alarcón, A; Fuentes Ferrer, M E; Carreras-Delgado, J L

2015-01-01

To compare axillary involvement (N+) at initial staging in locally advanced breast cancer (LABC) with axillary lymphadenectomy histologic results after neoadjuvant chemotherapy treatment (NeoChemo). Retrospective study between November 2011 and September 2013 of LABC cases treated with neoadjuvant chemotherapy based on docetaxel (associated with trastuzumab in HER2 positive cases and carboplatin/adriamycin in HER2 negative cases). Those clinically or radiologically suspected cases of axillary involvement were histologically confirmed. When there was no suspicion of axillary involvement, sentinel lymph node radioguided biopsy (SLNRB) was performed using intradermal injection of (99m)Tc-nanocolloid albumin prior to neoadjuvant treatment. Axillary lymphadenectomy after NeoChemo was undertaken in all cases with positive axilla. Final pathologic response was classified as complete (pCR) when there was no evidence of tumoral disease and as non-pathologic complete response (no pCR) in the opposite case. A total of 346 patients treated with docetaxel were reviewed, identifying 105 LABC. Axillary involvement at initial staging was detected in 70 (67%) before starting NeoChemo. From these 70, 73% (n=51) were N+ (fine needle biopsy and/or biopsy) and the remaining 19 (27%) were occult N+ detected by SLNRB. Axillary lymphadenectomy detected pCR in 56% (39/70), increasing up to 84% pCR when initial N+ status was reached using SNLB. On the other hand, when N+ was detected using fine needle biopsy/lymph biopsy, pCR was only 45%. More than 50% of women affected by locally advanced breast cancer with tumoral axillary involvement at initial diagnosis present free metastatic axilla after therapeutic neoadjuvant chemotherapy effect. This increases up to almost 90% in case of occult metastatic axilla detected with sentinel node biopsy prior starting neoadjuvant chemotherapy. Copyright © 2014 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

Biological Image-Guided Radiotherapy in Rectal Cancer: Challenges and Pitfalls

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

Roels, Sarah; Slagmolen, Pieter; Nuyts, Johan

2009-11-01

Purpose: To investigate the feasibility of integrating multiple imaging modalities for image-guided radiotherapy in rectal cancer. Patients and Methods: Magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) were performed before, during, and after preoperative chemoradiotherapy (CRT) in patients with resectable rectal cancer. The FDG-PET signals were segmented with an adaptive threshold-based and a gradient-based method. Magnetic resonance tumor volumes (TVs) were manually delineated. A nonrigid registration algorithm was applied to register the images, and mismatch analyses were carried out between MR and FDG-PET TVs and between TVs over time. Tumor volumes delineated on the images after CRTmore » were compared with the pathologic TV. Results: Forty-five FDG-PET/CT and 45 MR images were analyzed from 15 patients. The mean MRI and FDG-PET TVs showed a tendency to shrink during and after CRT. In general, MRI showed larger TVs than FDG-PET. There was an approximately 50% mismatch between the FDG-PET TV and the MRI TV at baseline and during CRT. Sixty-one percent of the FDG-PET TV and 76% of the MRI TV obtained after 10 fractions of CRT remained inside the corresponding baseline TV. On MRI, residual tumor was still suspected in all 6 patients with a pathologic complete response, whereas FDG-PET showed a metabolic complete response in 3 of them. The FDG-PET TVs delineated with the gradient-based method matched closest with pathologic findings. Conclusions: Integration of MRI and FDG-PET into radiotherapy seems feasible. Gradient-based segmentation is recommended for FDG-PET. Spatial variance between MRI and FDG-PET TVs should be taken into account for target definition.« less

Student diversity and implications for clinical competency development amongst domestic and international speech-language pathology students.

PubMed

Attrill, Stacie; Lincoln, Michelle; McAllister, Sue

2012-06-01

International students graduating from speech-language pathology university courses must achieve the same minimum competency standards as domestic students. This study aimed to collect descriptive information about the number, origin, and placement performance of international students as well as perceptions of the performance of international students on placement. University Clinical Education Coordinators (CECs), who manage clinical placements in eight undergraduate and six graduate entry programs across the 10 participating universities in Australia and New Zealand completed a survey about 3455 international and domestic speech-language pathology students. Survey responses were analysed quantitatively and qualitatively with non-parametric statistics and thematic analysis. Results indicated that international students came from a variety of countries, but with a regional focus on the countries of Central and Southern Asia. Although domestic students were noted to experience significantly less placement failure, fewer supplementary placements, and reduced additional placement support than international students, the effect size of these relationships was consistently small and therefore weak. CECs rated international students as more frequently experiencing difficulties with communication competencies on placement. However, CECs qualitative comments revealed that culturally and linguistically diverse (CALD) students may experience more difficulties with speech-language pathology competency development than international students. Students' CALD status should be included in future investigations of factors influencing speech-language pathology competency development.

[The case of completed pregnancy of the patient with Dandy-Walker malformation].

PubMed

Beliaeva, E V; Lapshina, L V; Shaposhnikova, E V; Molgachev, A A

2018-01-01

Dandy-Walker malformation is a rare disease of the central nervous system pathology (congenital malformations of the fossa cranii posterior). The key features of this syndrome are an enlargement of the fourth ventricle; complete absence of the cerebellar vermis, the posterior midline area of cerebellar cortex responsible for coordination of the axial musculature; and cyst formation near the internal base of the skull. Pregnant patients with Dandy-Walker malformation are at high risk and are managed by multidisciplinary teams including neurologists and obstetricians. We present a case report of full-term pregnancy and uncomplicated delivery in a women with Dandy-Walker malformation.

Phase II Study of Gemcitabine, Carboplatin, and Iniparib As Neoadjuvant Therapy for Triple-Negative and BRCA1/2 Mutation–Associated Breast Cancer With Assessment of a Tumor-Based Measure of Genomic Instability: PrECOG 0105

PubMed Central

Telli, Melinda L.; Jensen, Kristin C.; Vinayak, Shaveta; Kurian, Allison W.; Lipson, Jafi A.; Flaherty, Patrick J.; Timms, Kirsten; Abkevich, Victor; Schackmann, Elizabeth A.; Wapnir, Irene L.; Carlson, Robert W.; Chang, Pei-Jen; Sparano, Joseph A.; Head, Bobbie; Goldstein, Lori J.; Haley, Barbara; Dakhil, Shaker R.; Reid, Julia E.; Hartman, Anne-Renee; Manola, Judith; Ford, James M.

2015-01-01

Purpose This study was designed to assess efficacy, safety, and predictors of response to iniparib in combination with gemcitabine and carboplatin in early-stage triple-negative and BRCA1/2 mutation–associated breast cancer. Patients and Methods This single-arm phase II study enrolled patients with stage I to IIIA (T ≥ 1 cm) estrogen receptor–negative (≤ 5%), progesterone receptor–negative (≤ 5%), and human epidermal growth factor receptor 2–negative or BRCA1/2 mutation–associated breast cancer. Neoadjuvant gemcitabine (1,000 mg/m2 intravenously [IV] on days 1 and 8), carboplatin (area under curve of 2 IV on days 1 and 8), and iniparib (5.6 mg/kg IV on days 1, 4, 8, and 11) were administered every 21 days for four cycles, until the protocol was amended to six cycles. The primary end point was pathologic complete response (no invasive carcinoma in breast or axilla). All patients underwent comprehensive BRCA1/2 genotyping, and homologous recombination deficiency was assessed by loss of heterozygosity (HRD-LOH) in pretreatment core breast biopsies. Results Among 80 patients, median age was 48 years; 19 patients (24%) had germline BRCA1 or BRCA2 mutations; clinical stage was I (13%), IIA (36%), IIB (36%), and IIIA (15%). Overall pathologic complete response rate in the intent-to-treat population (n = 80) was 36% (90% CI, 27 to 46). Mean HRD-LOH scores were higher in responders compared with nonresponders (P = .02) and remained significant when BRCA1/2 germline mutations carriers were excluded (P = .021). Conclusion Preoperative combination of gemcitabine, carboplatin, and iniparib is active in the treatment of early-stage triple-negative and BRCA1/2 mutation–associated breast cancer. The HRD-LOH assay was able to identify patients with sporadic triple-negative breast cancer lacking a BRCA1/2 mutation, but with an elevated HRD-LOH score, who achieved a favorable pathologic response. Confirmatory controlled trials are warranted. PMID:25847929

DNA Repair Biomarkers Predict Response to Neoadjuvant Chemoradiotherapy in Esophageal Cancer

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

Alexander, Brian M., E-mail: bmalexander@lroc.harvard.edu; Wang Xiaozhe; Niemierko, Andrzej

2012-05-01

Purpose: The addition of neoadjuvant chemoradiotherapy prior to surgical resection for esophageal cancer has improved clinical outcomes in some trials. Pathologic complete response (pCR) following neoadjuvant therapy is associated with better clinical outcome in these patients, but only 22% to 40% of patients achieve pCR. Because both chemotherapy and radiotherapy act by inducing DNA damage, we analyzed proteins selected from multiple DNA repair pathways, using quantitative immunohistochemistry coupled with a digital pathology platform, as possible biomarkers of treatment response and clinical outcome. Methods and Materials: We identified 79 patients diagnosed with esophageal cancer between October 1994 and September 2002, withmore » biopsy tissue available, who underwent neoadjuvant chemoradiotherapy prior to surgery at the Massachusetts General Hospital and used their archived, formalin-fixed, paraffin-embedded biopsy samples to create tissue microarrays (TMA). TMA sections were stained using antibodies against proteins in various DNA repair pathways including XPF, FANCD2, PAR, MLH1, PARP1, and phosphorylated MAPKAP kinase 2 (pMK2). Stained TMA slides were evaluated using machine-based image analysis, and scoring incorporated both the intensity and the quantity of positive tumor nuclei. Biomarker scores and clinical data were assessed for correlations with clinical outcome. Results: Higher scores for MLH1 (p = 0.018) and lower scores for FANCD2 (p = 0.037) were associated with pathologic response to neoadjuvant chemoradiation on multivariable analysis. Staining of MLH1, PARP1, XPF, and PAR was associated with recurrence-free survival, and staining of PARP1 and FANCD2 was associated with overall survival on multivariable analysis. Conclusions: DNA repair proteins analyzed by immunohistochemistry may be useful as predictive markers for response to neoadjuvant chemoradiotherapy in patients with esophageal cancer. These results are hypothesis generating and need confirmation in an independent data set.« less

Prospective study of neoadjuvant chemoradiotherapy using intensity-modulated radiotherapy and 5 fluorouracil for locally advanced rectal cancer – toxicities and response assessment

PubMed Central

Simson, David K; Mitra, Swarupa; Ahlawat, Parveen; Saxena, Upasna; Sharma, Manoj Kumar; Rawat, Sheh; Singh, Harpreet; Bansal, Babita; Sripathi, Lalitha Kameshwari; Tanwar, Aditi

2018-01-01

Aims and objectives The past 2 decades witnessed the strengthening of evidence favoring the role of neoadjuvant chemoradiation (CHRT) in the treatment of locally advanced rectal cancer. The study aims to evaluate the response and acute toxicities to neoadjuvant CHRT using intensity-modulated radiotherapy (IMRT) in the treatment of rectal cancer. Predictive factors to achieve pathological complete response (pCR) were analyzed, as a secondary endpoint. Materials and methods All consecutive patients who underwent IMRT as part of neoadjuvant CHRT in the treatment of rectal cancer between August 2014 and December 2016 at a tertiary cancer care center were accrued for the study. The cohort underwent CHRT with IMRT technique at a dose of 50.4 Gy in 28 fractions concurrent with continuous infusion of 5 fluorouracil during the first and the last 4 days of CHRT. Surgery was performed 6 weeks later and the pathological response to CHRT was noted. Results Forty-three subjects were accrued for the study. Radiation dermatitis and diarrhea were the only observed grade ≥3 acute toxicities. Sphincter preservation rate (SPR) was 43.3%. pCR was observed in 32.6%. Univariate and multivariate logistic regression showed that carcinoembryonic antigen was the only independent predictive factor to achieve pCR. Conclusion IMRT as part of neoadjuvant CHRT in the treatment of locally advanced rectal cancer is well tolerated and gives comparable results with respect to earlier studies in terms of pathological response and SPR. Further randomized controlled studies are needed to firmly state that IMRT is superior to 3-dimensional conformal radiotherapy. PMID:29593430

RECIST 1.1-Update and clarification: From the RECIST committee.

PubMed

Schwartz, Lawrence H; Litière, Saskia; de Vries, Elisabeth; Ford, Robert; Gwyther, Stephen; Mandrekar, Sumithra; Shankar, Lalitha; Bogaerts, Jan; Chen, Alice; Dancey, Janet; Hayes, Wendy; Hodi, F Stephen; Hoekstra, Otto S; Huang, Erich P; Lin, Nancy; Liu, Yan; Therasse, Patrick; Wolchok, Jedd D; Seymour, Lesley

2016-07-01

The Response Evaluation Criteria in Solid Tumours (RECIST) were developed and published in 2000, based on the original World Health Organisation guidelines first published in 1981. In 2009, revisions were made (RECIST 1.1) incorporating major changes, including a reduction in the number of lesions to be assessed, a new measurement method to classify lymph nodes as pathologic or normal, the clarification of the requirement to confirm a complete response or partial response and new methodologies for more appropriate measurement of disease progression. The purpose of this paper was to summarise the questions posed and the clarifications provided as an update to the 2009 publication. Copyright © 2016. Published by Elsevier Ltd.

High levels of serum CA15-3 and residual invasive tumor size are associated with poor prognosis for breast cancer patients with non-pathological complete response after neoadjuvant chemotherapy.

PubMed

Fujimoto, Yukie; Higuchi, Tomoko; Nishimukai, Arisa; Miyagawa, Yoshimasa; Kira, Ayako; Ozawa, Hiromi; Bun, Ayako; Imamura, Michiko; Miyoshi, Yasuo

2018-06-24

To identify surrogate markers for prognosis of breast cancer patients with non-pathological complete response (non-pCR) to neoadjuvant chemotherapy (NAC), our investigation focused on serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA15-3) as well as clinicopathological factors both pre- and post-NAC. A total of 185 breast cancer patients treated with NAC were recruited. Serum CEA and CA15-3 were measured at baseline and at completion of NAC. Among the non-pCR cancers (n = 142), disease-free survival (DFS) of patients with CA15-3-low at baseline (3-year DFS: 0.908, n = 73) was significantly better than of those with CA15-3-high (3-year DFS: 0.681, n = 69, P = 0.0134). Multivariable analysis demonstrated that baseline CA15-3 levels (hazard ratio (HR): 3.31, 95% confidence interval (CI): 1.28-10.23; P = 0.0122) and residual invasive size (HR: 4.47, 1.26-28.39; P = 0.0171) were significant independent factors for DFS. The combination of these factors proved to be accurate predictor for DFS regardless of breast cancer subtypes. The combination of residual invasive size and serum CA15-3 levels at baseline seems to be a significant and independent surrogate marker of poor outcome for patients with non-pCR. These findings suggest that these markers may be useful for identifying patients with inferior prognosis and candidates for additional adjuvant treatments. © 2018 Wiley Periodicals, Inc.

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

PubMed

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

2015-05-23

A progressive loss of circulating anti-human epidermal growth factor receptor-2/neu (HER2) CD4(+) T-helper type 1 (Th1) immune responses is observed in HER2(pos)-invasive breast cancer (IBC) patients relative to healthy controls. Pathologic complete response (pCR) following neoadjuvant trastuzumab and chemotherapy (T + C) is associated with decreased recurrence and improved prognosis. We examined differences in anti-HER2 Th1 responses between pCR and non-pCR patients to identify modifiable immune correlates to pathologic response following neoadjuvant T + C. Anti-HER2 Th1 responses in 87 HER2(pos)-IBC patients were examined using peripheral blood mononuclear cells pulsed with 6 HER2-derived class II peptides via IFN-γ ELISPOT. Th1 response metrics were anti-HER2 responsivity, repertoire (number of reactive peptides), and cumulative response across 6 peptides (spot-forming cells [SFC]/10(6) cells). Anti-HER2 Th1 responses of non-pCR patients (n = 4) receiving adjuvant HER2-pulsed type 1-polarized dendritic cell (DC1) vaccination were analyzed pre- and post-immunization. Depressed anti-HER2 Th1 responses observed in treatment-naïve HER2(pos)-IBC patients (n = 22) did not improve globally in T + C-treated HER2(pos)-IBC patients (n = 65). Compared with adjuvant T + C receipt, neoadjuvant T + C - utilized in 61.5 % - was associated with higher anti-HER2 Th1 repertoire (p = 0.048). While pCR (n = 16) and non-pCR (n = 24) patients did not differ substantially in demographic/clinical characteristics, pCR patients demonstrated dramatically higher anti-HER2 Th1 responsivity (94 % vs. 33 %, p = 0.0002), repertoire (3.3 vs. 0.3 peptides, p < 0.0001), and cumulative response (148.2 vs. 22.4 SFC/10(6), p < 0.0001) versus non-pCR patients. After controlling for potential confounders, anti-HER2 Th1 responsivity remained independently associated with pathologic response (odds ratio 8.82, p = 0.016). This IFN-γ(+) immune disparity was mediated by anti-HER2 CD4(+)T-bet(+)IFN-γ(+) (i.e., Th1) - not CD4(+)GATA-3(+)IFN-γ(+) (i.e., Th2) - phenotypes, and not attributable to non-pCR patients' immune incompetence, host-level T-cell anergy, or increased immunosuppressive populations. In recruited non-pCR patients, anti-HER2 Th1 repertoire (3.7 vs. 0.5, p = 0.014) and cumulative response (192.3 vs. 33.9 SFC/10(6), p = 0.014) improved significantly following HER2-pulsed DC1 vaccination. Anti-HER2 CD4(+) Th1 response is a novel immune correlate to pathologic response following neoadjuvant T + C. In non-pCR patients, depressed Th1 responses are not immunologically "fixed" and can be restored with HER2-directed Th1 immune interventions. In such high-risk patients, combining HER2-targeted therapies with strategies to boost anti-HER2 Th1 immunity may improve outcomes and mitigate recurrence.

SU-F-R-47: Quantitative Shape Relationship Analysis of PTV Modification for Critical Anatomy Sparing and Its Impact On Pathologic Response for Neoadjuvant Stereotactic Radiotherapy for Pancreatic Cancer

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

Cheng, Z; Rosati, L; Chen, L

Purpose: Stereotactic body radiation therapy (SBRT) may be used to increase surgery candidacy in borderline resectable (BRPC) and locally advanced (LAPC) pancreatic cancer. However, the planning target volume (PTV) may need to be limited to avoid toxicity when the gross tumor volume (GTV) is anatomically involved with surrounding critical structures. Our study aims to characterize the coverage of GTV and investigate the association between modified PTV and pathologic (pCR) or near pathologic (npCR) complete response rates determined from the surgical specimen. Methods: Patients treated with neoadjuvant pancreas SBRT followed by surgery from 2010–2015 were selected from Oncospace. Overlap volume histogrammore » (OVH) analysis was performed to determine the extent of compromise of the PTV from both the GTV and a standard target (GTV+3mm). Subsequently, normalized overlap volume (%) was calculated for: (1) GTV-PTV, and (2) GTV+3mm expansion-PTV. A logistic regression model was used to identify the association between the overlap ratios and ≥ npCR(pCR/npCR) stratified by active breathing control (ABC) versus free-breathing status. Results: Eighty-one (BRPC: n=42, LAPC: n=39) patients were available for analysis. Nearly 40% (31/81) had ≥npCR and 75% (61/81) were able to complete ABC. Mean coverage of the GTV-PTV was 92.6% (range, 59.9%–100%, SD = 8.68) and coverage of the GTV+3mm expansion-PTV was 85. 2% (range, 59.9% −100.0%, SD= 8.67). Among the patients with ABC, every 10% increase in GTV coverage doubled the odds to have ≥npCR (OR = 1.82, p=0.06). Coverage of GTV+3mm expansion was not associated with ≥npCR regardless of ABC status. Conclusion: Preferential sparing of critical anatomy over GTV-PTV coverage with ABC management suggests worse ≥npCR rates for neoadjuvant SBRT in BRPC and LAPC. Limiting the GTV and GTV+3mm expansion in free-breathing patients was not associated with pathologic response perhaps due to larger GTV definitions as a result of motion artifacts in free-breathing CT scans. Collaboration with Toshiba, Elekta, and Phillips.« less

Prognostic Effect of Carcinoma In Situ in Muscle-invasive Urothelial Carcinoma Patients Receiving Neoadjuvant Chemotherapy

PubMed Central

Thomas, Derek E.; Kaimakliotis, Hristos Z.; Rice, Kevin R.; Pereira, Jose A.; Johnston, Paul; Moore, Marietta L.; Reed, Angela; Cregar, Dylan M.; Franklin, Cindy; Loman, Rhoda L.; Koch, Michael O.; Bihrle, Richard; Foster, Richard S.; Masterson, Timothy A.; Gardner, Thomas A.; Sundaram, Chandru P.; Powell, Charles R.; Beck, Stephen D.W.; Grignon, David J.; Cheng, Liang; Albany, Costantine; Hahn, Noah M.

2017-01-01

We performed a single-institution retrospective analysis of 137 patients with muscle-invasive urothelial carcinoma who underwent neoadjuvant chemotherapy and radical cystectomy to assess the prognostic significance of carcinoma in situ (CIS). The pathologic complete response rates were significantly decreased for patients with CIS identified on transurethral resection of the bladder tumor before treatment. The long-term follow-up data from patients with isolated CIS at cystectomy revealed prolonged progression-free and overall survival. Background Carcinoma in situ (CIS) is a poor prognostic finding in urothelial carcinoma. However, its significance in muscle-invasive urothelial carcinoma (MIUC) treated with neoadjuvant chemotherapy (NAC) is uncertain. We assessed the effect of CIS found in pretreatment transurethral resection of bladder tumor (TURBT) biopsies on the pathologic and clinical outcomes. Materials and Methods Subjects with MIUC treated with NAC before cystectomy were identified. The pathologic complete response (pCR) rates stratified by TURBT CIS status were compared. The secondary analyses included tumor response, progression-free survival (PFS), overall survival (OS), and an exploratory post hoc analysis of patients with pathologic CIS only (pTisN0) at cystectomy. Results A total of 137 patients with MIUC were identified. TURBT CIS was noted in 30.7% of the patients. The absence of TURBT CIS was associated with a significantly increased pCR rate (23.2% vs. 9.5%; odds ratio, 4.08; 95% confidence interval, 1.19–13.98; P = .025). Stage pTisN0 disease was observed in 19.0% of the TURBT CIS patients. TURBT CIS status did not significantly affect the PFS or OS outcomes. Post hoc analysis of the pTisN0 patients revealed prolonged median PFS (104.5 vs. 139.9 months; P = .055) and OS (104.5 vs. 152.3 months; P = .091) outcomes similar to those for the pCR patients. Conclusion The absence of CIS on pretreatment TURBT in patients with MIUC undergoing NAC was associated with increased pCR rates, with no observed differences in PFS or OS. Isolated CIS at cystectomy was frequently observed, with lengthy PFS and OS durations similar to those for pCR patients. Further studies aimed at understanding the biology and clinical effect of CIS in MIUC are warranted. PMID:28040424

Opportunities for Improvement in Pathology Reporting of Childhood Nonrhabdomyosarcoma Soft Tissue Sarcomas:  A Report From Children's Oncology Group (COG) Study ARST0332.

PubMed

Black, Jennifer O; Coffin, Cheryl M; Parham, David M; Hawkins, Douglas S; Speights, Rose A; Spunt, Sheri L

2016-09-01

Treatment of soft tissue tumors in young patients relies on the diagnostic information conveyed in the pathology report. We examined pathology reports from Children's Oncology Group ARST0332 for inclusion of data elements required in published guidelines. Pathology reports for 551 eligible patients were examined for required data elements defined by the College of American Pathologists, including tissue type, procedure, tumor site, tumor maximum diameter, macroscopic extent of tumor, histologic type, mitotic rate, extent of necrosis, tumor grade, margin status, use of ancillary studies, and pathologic stage. Only 65 (12%) of 551 reports included all required data elements. Of reports containing synoptic templates, 57% were complete. This study reveals significant opportunity to improve the quality of pathology reports in young patients with soft tissue tumors. Use of templates or checklists improves completeness of reports. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Predicting response before initiation of neoadjuvant chemotherapy in breast cancer using new methods for the analysis of dynamic contrast enhanced MRI (DCE MRI) data

NASA Astrophysics Data System (ADS)

DeGrandchamp, Joseph B.; Whisenant, Jennifer G.; Arlinghaus, Lori R.; Abramson, V. G.; Yankeelov, Thomas E.; Cárdenas-Rodríguez, Julio

2016-03-01

The pharmacokinetic parameters derived from dynamic contrast enhanced (DCE) MRI have shown promise as biomarkers for tumor response to therapy. However, standard methods of analyzing DCE MRI data (Tofts model) require high temporal resolution, high signal-to-noise ratio (SNR), and the Arterial Input Function (AIF). Such models produce reliable biomarkers of response only when a therapy has a large effect on the parameters. We recently reported a method that solves the limitations, the Linear Reference Region Model (LRRM). Similar to other reference region models, the LRRM needs no AIF. Additionally, the LRRM is more accurate and precise than standard methods at low SNR and slow temporal resolution, suggesting LRRM-derived biomarkers could be better predictors. Here, the LRRM, Non-linear Reference Region Model (NRRM), Linear Tofts model (LTM), and Non-linear Tofts Model (NLTM) were used to estimate the RKtrans between muscle and tumor (or the Ktrans for Tofts) and the tumor kep,TOI for 39 breast cancer patients who received neoadjuvant chemotherapy (NAC). These parameters and the receptor statuses of each patient were used to construct cross-validated predictive models to classify patients as complete pathological responders (pCR) or non-complete pathological responders (non-pCR) to NAC. Model performance was evaluated using area under the ROC curve (AUC). The AUC for receptor status alone was 0.62, while the best performance using predictors from the LRRM, NRRM, LTM, and NLTM were AUCs of 0.79, 0.55, 0.60, and 0.59 respectively. This suggests that the LRRM can be used to predict response to NAC in breast cancer.

Identification of residual breast carcinoma following neoadjuvant chemotherapy: diffusion-weighted imaging--comparison with contrast-enhanced MR imaging and pathologic findings.

PubMed

Woodhams, Reiko; Kakita, Satoko; Hata, Hirofumi; Iwabuchi, Keiichi; Kuranami, Masaru; Gautam, Shiva; Hatabu, Hiroto; Kan, Shinichi; Mountford, Carolyn

2010-02-01

To compare the capability of diffusion-weighted (DW) and contrast material-enhanced magnetic resonance (MR) imaging to provide diagnostic information on residual breast cancers following neoadjuvant chemotherapy and to assess apparent diffusion coefficients (ADCs) of the carcinoma prior to neoadjuvant chemotherapy to determine if the method could help predict response to chemotherapy. Institutional review board approval and informed consent were obtained. Three hundred ninety-eight patients underwent MR imaging of the breast, including DW MR (b values, 0 and 1500 sec/mm(2)) and contrast-enhanced MR imaging. Of these, the contralateral breast in 73 women was used as a control. Seventy-two patients with 73 lesions with malignant disease were treated by using neoadjuvant chemotherapy and were examined for residual disease following therapy. Three were excluded because of prolonged intervals between final MR imaging and surgery. Thus, 69 patients (70 lesions) with DW and contrast-enhanced MR imaging results were compared with postoperative histopathologic findings. The ADCs of the carcinoma prior to neoadjuvant chemotherapy were calculated for each patient, and those with complete response and residual disease were compared. The accuracy for depicting residual tumor was 96% for DW MR imaging, compared with an accuracy of 89% for contrast-enhanced MR imaging (P = .06). There was no significant difference in prechemotherapy ADCs between pathologic complete response cases and those with residual disease. DW MR imaging had at least as good of accuracy as did contrast-enhanced MR imaging for monitoring neoadjuvant chemotherapy. The ADCs prior to chemotherapy did not predict response to chemotherapy. The use of DW imaging to visualize residual breast cancer without the need for contrast medium could be advantageous in women with impaired renal function. (c) RSNA, 2010

Development of a Chinese version of the Western Ontario Meniscal Evaluation Tool: cross-cultural adaptation and psychometric evaluation.

PubMed

Tong, W W; Wang, W; Xu, W D

2016-08-15

The Western Ontario Meniscal Evaluation Tool (WOMET) is a questionnaire designed to evaluate the health-related quality of life (HRQOL) of patients with meniscal pathology. Our study aims to culturally adapt and validate the WOMET into a Chinese version. We translated the WOMET into Chinese. Then, a total of 121 patients with meniscal pathology were invited to participate in this study. To assess the test-retest reliability, the Chinese version WOMET was completed twice at 7-day intervals by the participants. The construct validity was assessed using Pearson's correlation coefficient or Spearman's correlation to test for correlations among the Chinese version WOMET and the eight domains of Short Form-36 (SF-36), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the International Knee Documentation Committee (IKDC) score. Responsiveness was tested by comparison of the preoperative and postoperative scores of the Chinese version WOMET. The test-retest reliability of the overall scale and different domains were all found to be excellent. The Cronbach's α was 0.90. The Chinese version WOMET correlated well with other questionnaires which suggested good construct validity. We observed no ceiling and floor effects of the Chinese version WOMET. We also found good responsiveness for the effect size, and the standardized response mean values were 0.86 and 1.11. The Chinese version of the WOMET appears to be reliable and valid in evaluating patients with meniscal pathology.

Preoperative Accelerated Partial Breast Irradiation for Early-Stage Breast Cancer: Preliminary Results of a Prospective, Phase 2 Trial

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

Nichols, Elizabeth, E-mail: Enichols1@umm.edu; Kesmodel, Susan B.; Bellavance, Emily

Purpose: To assess the feasibility of utilizing 3-dimensional conformal accelerated partial-breast irradiation (APBI) in the preoperative setting followed by standard breast-conserving therapy. Patients and Methods: This was a prospective trial testing the feasibility of preoperative APBI followed by lumpectomy for patients with early-stage invasive ductal breast cancer. Eligible patients had T1-T2 (<3 cm), N0 tumors. Patients received 38.5 Gy in 3.85-Gy fractions delivered twice daily. Surgery was performed >21 days after radiation therapy. Adjuvant therapy was given as per standard of care. Results: Twenty-seven patients completed treatment. With a median follow-up of 3.6 years (range, 0.5-5 years), there have been no local or regional failures.more » A complete pathologic response according to hematoxylin and eosin stains was seen in 4 patients (15%). There were 4 grade 3 seromas. Patient-reported cosmetic outcome was rated as good to excellent in 79% of patients after treatment. Conclusions: Preoperative 3-dimensional conformal radiation therapy−APBI is feasible and well tolerated in select patients with early-stage breast cancer, with no reported local recurrences and good to excellent cosmetic results. The pathologic response rates associated with this nonablative APBI dose regimen are particularly encouraging and support further exploration of this paradigm.« less

Effect of Neoadjuvant Radiation Dose on Surgical and Oncological Outcome in Locally Advanced Esophageal Cancer.

PubMed

Van Daele, E; Ceelen, W; Boterberg, T; Varinl, O; Van Nieuwenhove, Y; Putte, D Van de; Geboes, K; Pattyn, P

2015-01-01

Neoadjuvant chemoradiation (CRT) confers a survival benefit in locally advanced esophageal cancer. The optimal dose of radiotherapy remains undefined. From a prospective database, we identified patients who received CRT followed by Ivor Lewis esophagectomy. Surgical complications, pathological response, and oncological outcome were compared between patients who received a radiotherapy (RT) dose of 36 Gy (group1) versus a dose of > 40 Gy (group 1). 147 patients were evaluated: 109 received 36 Gy, while 38 received 41-50Gy. Mean age was 61 ± 9 years (84% male). Median hospital stay was 16 days. Anastomotic leakage occurred in 4.0%. Pulmonary complications occurred in 41.8%, neither being influenced by RT dose. Complete resection (R0) was achieved in 95% (group 1) and 100% (group 2), P = 0.3. Pathological complete response (pCR) was observed in 19% (group 1) and 37% (group 1), P = 0.04. Local recurrence developed in 9% in group 1, and 3% in group 2 (P = 0.3), but regional recurrence developed significantly higher in the low dose group (18% vs 3%, P < 0.001). Metastatic recurrence occurred in 48% in group 1 and 13% in group 1 (P < 0.001). In patients with locally advanced esophageal cancer a higher RT dose does not affect surgical outcome, enhances pCR rate, and reduces the locoregional and metastatic recurrence risk.

Pathologic Complete Response Predicts Recurrence-Free Survival More Effectively by Cancer Subset: Results From the I-SPY 1 TRIAL—CALGB 150007/150012, ACRIN 6657

PubMed Central

Esserman, Laura J.; Berry, Donald A.; DeMichele, Angela; Carey, Lisa; Davis, Sarah E.; Buxton, Meredith; Hudis, Cliff; Gray, Joe W.; Perou, Charles; Yau, Christina; Livasy, Chad; Krontiras, Helen; Montgomery, Leslie; Tripathy, Debasish; Lehman, Constance; Liu, Minetta C.; Olopade, Olufunmilayo I.; Rugo, Hope S.; Carpenter, John T.; Dressler, Lynn; Chhieng, David; Singh, Baljit; Mies, Carolyn; Rabban, Joseph; Chen, Yunn-Yi; Giri, Dilip; van 't Veer, Laura; Hylton, Nola

2012-01-01

Purpose Neoadjuvant chemotherapy for breast cancer provides critical information about tumor response; how best to leverage this for predicting recurrence-free survival (RFS) is not established. The I-SPY 1 TRIAL (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis) was a multicenter breast cancer study integrating clinical, imaging, and genomic data to evaluate pathologic response, RFS, and their relationship and predictability based on tumor biomarkers. Patients and Methods Eligible patients had tumors ≥ 3 cm and received neoadjuvant chemotherapy. We determined associations between pathologic complete response (pCR; defined as the absence of invasive cancer in breast and nodes) and RFS, overall and within receptor subsets. Results In 221 evaluable patients (median tumor size, 6.0 cm; median age, 49 years; 91% classified as poor risk on the basis of the 70-gene prognosis profile), 41% were hormone receptor (HR) negative, and 31% were human epidermal growth factor receptor 2 (HER2) positive. For 190 patients treated without neoadjuvant trastuzumab, pCR was highest for HR-negative/HER2-positive patients (45%) and lowest for HR-positive/HER2-negative patients (9%). Achieving pCR predicted favorable RFS. For 172 patients treated without trastuzumab, the hazard ratio for RFS of pCR versus no pCR was 0.29 (95% CI, 0.07 to 0.82). pCR was more predictive of RFS by multivariate analysis when subtype was taken into account, and point estimates of hazard ratios within the HR-positive/HER2-negative (hazard ratio, 0.00; 95% CI, 0.00 to 0.93), HR-negative/HER2-negative (hazard ratio, 0.25; 95% CI, 0.04 to 0.97), and HER2-positive (hazard ratio, 0.14; 95% CI, 0.01 to 1.0) subtypes are lower. Ki67 further improved the prediction of pCR within subsets. Conclusion In this biologically high-risk group, pCR differs by receptor subset. pCR is more highly predictive of RFS within every established receptor subset than overall, demonstrating that the extent of outcome advantage conferred by pCR is specific to tumor biology. PMID:22649152

Phase II study of neoadjuvant gemcitabine, pegylated liposomal doxorubicin, and docetaxel in locally advanced breast cancer.

PubMed

Artioli, Grazia; Grazia, Artioli; Mocellin, Simone; Simone, Mocellin; Borgato, Lucia; Lucia, Borgato; Cappetta, Alessandro; Alessandro, Cappetta; Bozza, Fernando; Fernando, Bozza; Zavagno, Giorgio; Giorgio, Zavagno; Zovato, Stefania; Stefania, Zovato; Marchet, Alberto; Alberto, Marchet; Pastorelli, Davide; Davide, Pastorelli

2010-09-01

This was a phase II study to assess the activity of a novel neoadjuvant regimen in locally-advanced breast cancer. Fifty patients with histological confirmation of locally advanced breast cancer received treatment with gemcitabine 1000 mg/m(2) (day 1) followed by gemcitabine 800 mg/m(2) plus docetaxel 75 mg/m(2) plus pegylated liposomal doxorubicin (PLD) 30 mg/m(2) (day 8) every 3 weeks for at least 4 cycles, plus a final 2 additional cycles. Tumour size was T1 (n=2), T2 (n=32), T3 (n=14), T4 (n=2). All 50 patients underwent surgery. Clinical complete, partial and no response were observed in 13 (26%), 24 (48%) and 11 (22%) patients, respectively (overall response rate: 74%). The number of chemotherapy cycles was found to be an independent predictor of a pathologic complete response. The combination of gemcitabine-docetaxel-PLD can yield high tumour response rates in patients with locally-advanced breast cancer who undergo a full treatment of 6 cycles.

Yttrium-90 radioembolization as a bridge to liver transplantation: a single-institution experience.

PubMed

Tohme, Samer; Sukato, Daniel; Chen, Hui-Wei; Amesur, Nikhil; Zajko, Albert B; Humar, Abhinav; Geller, David A; Marsh, James W; Tsung, Allan

2013-11-01

To evaluate our experience with the use of yttrium-90 ((90)Y) radioembolization in maintaining potential candidacy and, in some instances, downstaging hepatocellular carcinoma (HCC) that does not meet Milan criteria for liver transplantation. A retrospective review of 20 consecutive patients with HCC who were listed to receive a liver transplant and were treated with (90)Y radioembolization as a sole modality for locoregional "bridge" therapy was performed. Demographics, radiographic and pathologic response, survival, and recurrences were examined. Twenty-two (90)Y treatments were performed in 20 patients before transplantation. Median time from first treatment to transplantation was 3.5 months. HCC in 14 patients met the Milan criteria at the time of the first (90)Y treatment, and HCC in six did not. All cases that originally met the Milan criteria remained within the criteria before transplantation, and two of six patients whose disease did not meet the criteria (33%) had their disease successfully downstaged to meet the criteria. Overall, nine patients (45%) had complete or partial radiologic response to (90)Y radioembolization according to modified Response Evaluation Criteria In Solid Tumors. Complete necrosis of tumor with no evidence of viable tumor on pathologic examination was observed in five patients (36%) whose disease met the Milan criteria. Particularly in regions with long wait list times, (90)Y treatment is effective in maintaining tumor size in potential liver transplantation candidates with HCC. In addition, it can also be considered as a downstaging therapy in select patients before transplantation. © SIR, 2013.

Perioperative BRAF inhibitors in locally advanced stage III melanoma.

PubMed

Zippel, Douglas; Markel, Gal; Shapira-Frommer, Roni; Ben-Betzalel, Guy; Goitein, David; Ben-Ami, Eytan; Nissan, Aviram; Schachter, Jacob; Schneebaum, Schlomo

2017-12-01

Stage III malignant melanoma is a heterogeneous disease where those cases deemed marginally resectable or irresecatble are frequently incurable by surgery alone. Targeted therapy takes advantage of the high incidence of BRAF mutations in melanomas, most notably the V600E mutation. These agents have rarely been used in a neoadjuvant setting prior to surgery. Thirteen consecutive patients with confirmed BRAF V600E regionally advanced melanoma deemed marginally resectable or irrresectable, were treated with BRAF inhibiting agents, prior to undergoing surgery. The primary outcome measures were a successful resection and pathological response. Disease-free survival was a secondary outcome measure. Overall, 12/13 patients showed a marked clinical responsiveness to medical treatment, enabling a macroscopically successful resection in all cases. Four patients had a complete pathological response with no viable tumor evident in the resected specimens and eight patients showed evidence of minimally residual tumor with extensive tumoral necrosis and fibrosis. One patient progressed and died before surgery. At a median follow up of 20 months, 10 patients remain free of disease. Perioperative treatment with BRAF inhibiting agents in BRAFV600E mutated Stage III melanoma patients facilitates surgical resection and affords satisfactory disease free survival. © 2017 Wiley Periodicals, Inc.

Clinical utility of pretreatment prediction of chemoradiotherapy response in rectal cancer: a review.

PubMed

Yoo, Byong Chul; Yeo, Seung-Gu

2017-03-01

Approximately 20% of all patients with locally advanced rectal cancer experience pathologically complete responses following neoadjuvant chemoradiotherapy (CRT) and standard surgery. The utility of radical surgery for patients exhibiting good CRT responses has been challenged. Organ-sparing strategies for selected patients exhibiting complete clinical responses include local excision or no immediate surgery. The subjects of this tailored management are patients whose presenting disease corresponds to current indications of neoadjuvant CRT, and their post-CRT tumor response is assessed by clinical and radiological examinations. However, a model predictive of the CRT response, applied before any treatment commenced, would be valuable to facilitate such a personalized approach. This would increase organ preservation, particularly in patients for whom upfront CRT is not generally prescribed. Molecular biomarkers hold the greatest promise for development of a pretreatment predictive model of CRT response. A combination of clinicopathological, radiological, and molecular markers will be necessary to render the model robust. Molecular research will also contribute to the development of drugs that can overcome the radioresistance of rectal tumors. Current treatments for rectal cancer are based on the expected prognosis given the presenting disease extent. In the future, treatment schemes may be modified by including the predicted CRT response evaluated at presentation.

Neoadjuvant Chemotherapy versus Chemoradiation Prior to Esophagectomy: Impact on Rate of Complete Pathologic Response and Survival in Esophageal Cancer Patients.

PubMed

Samson, Pamela; Robinson, Clifford; Bradley, Jeffrey; Lockhart, A Craig; Puri, Varun; Broderick, Stephen; Kreisel, Daniel; Krupnick, A Sasha; Patterson, G Alexander; Meyers, Bryan; Crabtree, Traves

2016-12-01

The aim of this study was to evaluate differences in pathologic complete response (pCR) rates and overall survival among patients receiving either neoadjuvant chemotherapy or chemoradiation before esophagectomy for locally advanced esophageal cancer. Patients with esophageal cancer receiving either neoadjuvant chemotherapy or chemoradiation before esophagectomy were identified using the National Cancer Database. Univariate analysis compared patient, tumor, and postoperative outcome characteristics. Logistic regression was performed to identify variables associated with achieving pCR. Kaplan-Meier analysis was performed to compare overall median survival by neoadjuvant therapy type and pCR status. Finally, a Cox proportional hazards model was fitted to identify variables associated with increased mortality hazard. From 2006 to 2012, a total of 916 of 7338 of patients (12.5%) received neoadjuvant chemotherapy whereas 6422 (87.5%) received neoadjuvant chemoradiation. Patients who received neoadjuvant chemoradiation were more likely to achieve a pCR (17.2% versus 6.4%, p < 0.001) and less likely to have positive margins (5.6% versus 11.5%, p < 0.001) than were patients who received neoadjuvant chemotherapy, with no difference in 30- or 90-day mortality. Achieving a pCR was associated with improved overall median survival (59.5 ± 4.0 months versus 30.1 ± 0.76 months for those with persistent disease, p < 0.001). On logistic regression, neoadjuvant chemoradiation therapy was independently associated with achieving a pCR (OR = 2.75, 95% confidence interval: 2.01-3.77, p < 0.001). Despite improvement in the pCR rate with neoadjuvant chemoradiation, neoadjuvant therapy type was not independently associated with long-term survival (hazard ratio = 1.12; 95% confidence interval: 0.97-1.30, p = 0.12). Although neoadjuvant chemoradiation is more successful in downstaging esophageal cancer before esophagectomy, it was not independently prognostic for improved long-term survival. Other factors affecting long-term survival among pathologic complete responders and among patients with persistent disease should be investigated to clarify this association. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Cat-Scratch Disease: A Pitfall for Lymphoma Evaluation by FDG-PET/CT.

PubMed

Dubreuil, Julien; Dony, Arthur; Salles, Gilles; Traverse-Glehen, Alexandra; Giammarile, Francesco; Skanjeti, Andrea

2017-02-01

FDG-PET/CT is a standard of care in staging and response assessment of Hodgkin lymphoma. Hence, it is important to recognize pitfalls owing to the potential therapeutic impact. We report a case of a 29-year-old woman affected by stage III bulky Hodgkin lymphoma. The interim FDG-PET/CT showed a complete metabolic response. After three new cycles of chemotherapy, the patient showed fever and lymphadenopathy at clinic examination, PET/CT revealed several FDG uptakes at lymph nodes in inguinal and iliac region. Pathologic analyses, after biopsy and serologic examinations, led to the diagnosis of cat-scratch disease.

Chemoresistant Gestational Trophoblastic Neoplasia: A Case Report

PubMed Central

M, Sahana

2014-01-01

Gestational trophoblastic neoplasia (GTN) is a disease of women in reproductive age. It is one of the most chemotherapy responsive and highly curable cancer. It is diagnosed when there is clinical, radiologic, pathologic, and/or hormonal evidence of persistent or relapsed gestational trophoblastic disease. In most instances, it is cured by surgical evacuation of the uterus. If persistent, it is treated with chemotherapy which provides response in >90% of the cases. In the unresponsive persistent cases and if the women has completed her child bearing, hysterectomy is generally recommended. Here, we report a rare case of chemoresistant GTN which was confirmed to be placental-site trophoblastic tumour (PSTT) on biopsy. PMID:25177610

Professionals' perceptions about healthcare resources for co-occuring disorders in Spain.

PubMed

Roncero, Carlos; Vega, Pablo; Martínez-Raga, Jose; Barral, Carmen; Basurte-Villamor, Ignacio; Rodríguez-Cintas, Laia; Mesías, Beatriz; Grau-López, Lara; Casas, Miguel; Szerman, Nestor

2014-01-01

Since provision of integrated services for patients with dual pathology or dual disorders (coexistence of an addictive disorder and other psychiatric disorders) constitutes an important challenge, this study compared the perceptions of health-care professionals with the existing, current state of specific resources for patients with dual pathology in Spain. Epidemiological, observational, cross-sectional, multicenter study with a large, representative sample of health care professionals attending patients with dual pathology in treatment resources throughout Spain. Participants completed a specifically designed ad-hoc on-line questionnaire about their perceptions on the existence of available resources and treatment needs for patients with dual pathology. To compare professionals' perceptions with existing available resources, the same on-line questionnaire was also completed by commissioners and managers responsible for national and regional healthcare plans on drug abuse. A total of 659 professionals, mostly psychologists (43.40%) or psychiatrists (32.93%) agreed to participate in the study. The highest degree of concordance between the perceptions of professional and the actual situation was found regarding the existence of mental health and addiction networks (either separately or unified) (74.48%), followed by specific workshops (73.08%) and sub-acute inpatient units (67.38%), specific hospitalization units (66.26%), detoxification units (63.15%) and outpatient programs (60.73%). We detected a lower degree of agreement regarding specific occupational rehabilitation centers (59.34%) day hospitals (58.93%), day centers (57.88%), outpatient intermediate resources (48.87%), psychiatric acute admission units (46.54%) and therapeutic communities (43.77%). In addition, on average, health care professionals underestimated the number of resources present in their respective communities. Relevant differences exist between the perceptions of professional and existing available resources for dual pathology patients in Spain, thus supporting the need of additional efforts and strategies to establish a registry and clearly inform about available resources for patients with dual diagnosis.

Salvage radiotherapy in prostate cancer patients. Planning, treatment response and prognosis using (11)C-choline PET/CT.

PubMed

García, J R; Cozar, M; Soler, M; Bassa, P; Riera, E; Ferrer, J

2016-01-01

To assess the prognostic value of the therapeutic response by (11)C-choline PET/CT in prostate cancer patients with biochemical recurrence in which (11)C-choline PET/CT indicated radio-guided radiotherapy. The study included 37 patients initially treated with prostatectomy, who were treated due to biochemical recurrence. (11)C-choline PE/CT detected infra-diaphragmatic lymph-node involvement. All were selected for intensity modulated radiation therapy, escalating the dose according to the PET findings. One year after treatment patients underwent PSA and (11)C-choline PET/CT categorizing response (complete/partial/progression). Clinical/biochemical/image monitoring was performed until appearance of second relapse or 36 months in disease-free patients. (11)C-choline PET/CT could detect lymph nodes in all 37 patients. They were 18 (48.6%) of more than a centimetre in size and 19 (51.3%) with no pathological CT morphology: 9 (24.3%) with positive lymph nodes of around one centimetre and 10 (27.0%) only less than a centimetre in size. The response by (11)C-choline PET/CT was categorised one year after radiotherapy: 16 patients (43.2%) complete response; 15 (40.5%) partial response, and 6 (16.2%) progression. The response was concordant between the PSA result and (11)C-choline PET/CT in 32 patients (86.5%), and discordant in five (13.5%). New recurrence was detected in 12 patients (80%) with partial response, and 5 (31.2%) with complete response. The mean time to recurrence was 9 months after partial response, and 18 months after complete response (significant difference, p<.0001). (11)C-choline PET/CT allows the selection of patients with recurrent prostate cancer candidates for radiotherapy and to plan the technique. The evaluation of therapeutic response by (11)C-choline PET/CT has prognostic significance. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

A Phase II Trial of Neoadjuvant Preoperative Chemoradiotherapy With S-1 Plus Irinotecan and Radiation in Patients With Locally Advanced Rectal Cancer: Clinical Feasibility and Response Rate

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

Sato, Takeo; Ozawa, Heita; Hatate, Kazuhiko

Purpose: We aimed to validate our hypothesis that a preoperative chemoradiotherapy regimen with S-1 plus irinotecan is feasible, safe, and active for the management of locally advanced rectal cancer in a single-arm Phase II setting. Methods and Materials: Eligible patients had previously untreated, locally advanced rectal adenocarcinoma. Radiotherapy was administered in fractions of 1.8Gy/d for 25 days. S-1 was administered orally in a fixed daily dose of 80mg/m{sup 2} on Days 1 to 5, 8 to 12, 22 to 26, and 29 to 33. Irinotecan (80mg/m{sup 2}) was infused on Days 1, 8, 22, and 29. Four or more weeksmore » after the completion of the treatment, total mesorectal excision with lateral lymph node dissection was performed. The primary endpoint was the rate of completing treatment in terms of feasibility. The secondary endpoints were the response rate and safety. Results: We enrolled 43 men and 24 women in the study. The number of patients who completed treatment was 58 (86.6%). Overall, 46 patients (68.7%) responded to treatment and 24 (34.7%) had a complete histopathologic response. Three patients had Grade 3 leukopenia, and another three patients had Grade 3 neutropenia. Diarrhea was the most common type of nonhematologic toxicity: 3 patients had Grade 3 diarrhea. Conclusions: A preoperative regimen of S-1, irinotecan, and radiotherapy to the rectum was feasible, and it appeared safe and effective in this nonrandomized Phase II setting. It exhibited a low incidence of adverse events, a high rate of completion of treatment, and an extremely high rate of pathologic complete response.« less

[Review of influence of landing impact on human body (correction of boby) and its medical evaluation].

PubMed

Guo, Yao-yu; Tan, Cheng; Liu, Bing-kun; Jiang, Shi-zhong

2002-12-01

Landing impact is the dynamic factor that manned spaceship will inevitably meet after the mission has been completed, and impact force may cause damages to human tissues [correction of tissuses] and organs, even death. This paper described the characteristics of pathological and dynamic response of human body to landing impact, and discussed various related factors such as impact angle, fetters, design of cushion, harness and terrain condition. Medical evaluation of +Gx, +Gz, +/- Gy impacts were summarized.

The effects of implementing synoptic pathology reporting in cancer diagnosis: a systematic review.

PubMed

Sluijter, Caro E; van Lonkhuijzen, Luc R C W; van Slooten, Henk-Jan; Nagtegaal, Iris D; Overbeek, Lucy I H

2016-06-01

Pathology reporting is evolving from a traditional narrative report to a more structured synoptic report. Narrative reporting can cause misinterpretation due to lack of information and structure. In this systematic review, we evaluate the impact of synoptic reporting on completeness of pathology reports and quality of pathology evaluation for solid tumours. Pubmed, Embase and Cochrane databases were systematically searched to identify studies describing the effect of synoptic reporting implementation on completeness of reporting and quality of pathology evaluation of solid malignant tumours. Thirty-three studies met the inclusion criteria. All studies, except one, reported an increased overall completeness of pathology reports after introduction of synoptic reporting (SR). Most frequently studied cancers were breast (n = 9) and colorectal cancer (n = 16). For breast cancer, narrative reports adequately described 'tumour type' and 'nodal status'. Synoptic reporting resulted in improved description of 'resection margins', 'DCIS size', 'location' and 'presence of calcifications'. For colorectal cancer, narrative reports adequately reported 'tumour type', 'invasion depth', 'lymph node counts' and 'nodal status'. Synoptic reporting resulted in increased reporting of 'circumferential margin', 'resection margin', 'perineural invasion' and 'lymphovascular invasion'. In addition, increased numbers of reported lymph nodes were found in synoptic reports. Narrative reports of other cancer types described the traditional parameters adequately, whereas for 'resection margins' and '(lympho)vascular/perineural invasion', implementation of synoptic reporting was necessary. Synoptic reporting results in improved reporting of clinical relevant data. Demonstration of clinical impact of this improved method of pathology reporting is required for successful introduction and implementation in daily pathology practice.

Gambling pathology is associated with dampened cortisol response among men and women.

PubMed

Paris, J J; Franco, C; Sodano, R; Frye, C A; Wulfert, E

2010-02-09

Pathological gambling has many similarities to pharmacological addiction. Notably, both pathological gambling and drug addiction are characterized by aberrations in hypothalamic-pituitary-adrenal (HPA) axis responding. As well, there are indications that gender differences may play a role in these processes. Whether gender and/or HPA response are associated with pathological gambling was of interest. Recreational and pathological gamblers (15 men and 6 women per group) had the HPA factor, cortisol, assessed in saliva before and after watching a video of their preferred mode of gambling (slot machines, horse race betting, scratch-off tickets, blackjack, video poker, craps, sports betting, online casino games, or lottery tickets), and a video of neutral stimuli (a rollercoaster ride). Basal levels of salivary cortisol did not significantly differ among recreational and pathological gamblers. However, recreational gamblers demonstrated significantly increased salivary cortisol levels after the gambling and rollercoaster videos, whereas pathological gamblers demonstrated no salivary cortisol increase in response to either video stimulus. There was also a non-significant trend for women to have a greater cortisol response to video stimuli compared to men. These data suggest that pathological gambling is associated with hypoactive HPA response to gambling stimuli, similar to chronic drug exposure, and gender may contribute to this effect. Published by Elsevier Inc.

Feasibility of Cisplatin-Based Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer Patients With Diminished Renal Function.

PubMed

Koshkin, Vadim S; Barata, Pedro C; Rybicki, Lisa A; Zahoor, Haris; Almassi, Nima; Redden, Alicia M; Fergany, Amr F; Kaouk, Jihad; Haber, Georges-Pascal; Stephenson, Andrew J; Ornstein, Moshe C; Gilligan, Timothy; Garcia, Jorge A; Rini, Brian I; Grivas, Petros

2018-02-22

Cisplatin-based neoadjuvant chemotherapy (NAC) before radical cystectomy is the standard of care in muscle-invasive bladder cancer. There are limited data regarding chemotherapy tolerability and outcomes for patients with low glomerular filtration rate (GFR) who receive cisplatin-based NAC. A retrospective analysis of patients who received cisplatin-based NAC at Cleveland Clinic (2005-2016) was undertaken. Patients with pre-NAC GFR < 60 mL/min by either Cockcroft-Gault (CG) or Modification of Diet in Renal Disease (MDRD) formula were compared to patients with GFR ≥ 60 mL/min for NAC tolerability, pathologic complete and partial response (pPR), and the ability to undergo radical cystectomy. Thirty patients with low GFR (34-59 mL/min) and 94 patients with normal GFR (≥ 60 mL/min) were identified. Low GFR patients were older (median, 71 vs. 65 years), but other demographic and transurethral resection of bladder tumor characteristics were comparable. Low GFR patients more frequently had early NAC discontinuation (30% vs. 13%), NAC modifications (delays, dose reduction, or discontinuation, 66% vs. 40%), and cisplatin-based NAC administered in split doses (37% vs. 16%). No differences in NAC tolerability or outcomes were noted among low GFR patients receiving split-dose versus standard regimens. No differences were noted between low and normal GFR patients in NAC cycles (median, 3 for each), cystectomy rates (93% for each), time to cystectomy, and GFR change from baseline to after NAC. Pathologic complete response was higher among normal GFR patients (24% vs. 14%). Patients with low GFR had more NAC discontinuations and modifications, but most completed planned NAC cycles. For carefully selected patients with GFR < 60 mL/min, cisplatin-based NAC remains a treatment option. Copyright © 2018 Elsevier Inc. All rights reserved.

Early results of multicenter phase II trial of perioperative oxaliplatin and capecitabine without radiotherapy for high-risk rectal cancer: CORONA I study.

PubMed

Kamiya, T; Uehara, K; Nakayama, G; Ishigure, K; Kobayashi, S; Hiramatsu, K; Nakayama, H; Yamashita, K; Sakamoto, E; Tojima, Y; Kawai, S; Kodera, Y; Nagino, M

2016-06-01

Perioperative introduction of developed chemotherapy into the treatment strategy for locally advanced rectal cancer (LARC) may be a promising option. However, the most prevalent treatment for high-risk LARC remains preoperative chemoradiotherapy (CRT) in Western countries. A phase II trial was undertaken to evaluate safety and efficacy of perioperative XELOX without radiotherapy (RT) for patients with high-risk LARC. Patients received 4 cycles of XELOX before and after surgery, respectively. Primary endpoint was disease-free survival. We enrolled 41 patients between June 2012 and April 2014. The completion rate of the preoperative XELOX was 90.3%. Twenty-nine patients (70.7%) could start postoperative XELOX, 15 of these patients (51.7%) completed 4 cycles. Allergic reaction to oxaliplatin was experienced by 5 patients (17.2%) during postoperative XELOX. One patient received additional RT after preoperative XELOX. Consequently, the remaining 40 patients underwent primary resection. Major complications occurred in 6 of 40 patients (15.0%). Pathological complete response (pCR) rate was 12.2%, and good tumor regression was exhibited in 31.7%. N down-staging (cN+ to ypN0) and T down-staging were detected in 56.7% and 52.5%, respectively. Clinical T4 tumor was a predictor of poor pathological response (p < 0.001). We could show the favorable pCR rate after preoperative XELOX alone. However, the T and N down-staging rate was likely to be insufficient. When tumor regression is essential for curative resection, the use of preoperative CRT is likely to be recommended. For patients with massive LN metastasis, the additional Bev to NAC might be a promising option. Copyright © 2016 Elsevier Ltd. All rights reserved.

Blood oxygenation level-dependent (BOLD) contrast magnetic resonance imaging (MRI) for prediction of breast cancer chemotherapy response: a pilot study.

PubMed

Jiang, Lan; Weatherall, Paul T; McColl, Roderick W; Tripathy, Debu; Mason, Ralph P

2013-05-01

To determine whether a simple noninvasive method of assessing tumor oxygenation is feasible in the clinical setting and can provide useful, potentially predictive information. Tumor microcirculation and oxygenation play critical roles in tumor growth and responsiveness to cytotoxic treatment and may provide prognostic indicators for cancer therapy. Deoxyhemoglobin is paramagnetic and can serve as an endogenous contrast agent causing signal loss in echo planar magnetic resonance imaging (MRI) (blood oxygenation level-dependent [BOLD]-MRI). We used BOLD-MRI to provide early evaluation of response to neoadjuvant chemotherapy in patients with locally advanced breast cancer. MRI was performed on 11 patients with biopsy-proven malignancy. MRI exams were scheduled before, during, and after chemotherapy. The BOLD study applied a 6-minute oxygen breathing challenge. Seven patients successfully completed the exams. Before chemotherapy, BOLD contrast enhancement was observed in all tumors, but the patients, who ultimately had complete pathological response, exhibited a significantly higher BOLD response to oxygen breathing. We have successfully implemented an oxygen-breathing challenge BOLD contrast technique as part of the standard breast MRI exam in patients with locally advanced breast cancer. The preliminary observation that a large BOLD response correlated with better treatment response suggests a predictive capability for BOLD MRI. Copyright © 2012 Wiley Periodicals, Inc.

[A case of advanced gastric cancer with multiple liver metastases completely responding long term to paclitaxel plus S-1 therapy].

PubMed

Kanou, Mikihiro; Kurisu, Yoshihiro; Akagi, Shinji; Tanaka, Tomoko; Toge, Kunio

2010-01-01

A 69-year-old man was admitted to our hospital with complaints of loss of appetite, fatigue and dysphasia. Upper gastroscopy revealed advanced gastric cancer. Abdominal CT suggested liver metastases. At first we thought the liver metastases has been completely resected, but we found multiple liver metastases unexpectedly. So only total gastric resection and liver biopsy were performed. The pathological diagnosis was metastatic carcinoma. Paclitaxel (PTX) and S-1 combination chemotherapy was started after operation and was continued for 42 courses. A CT scan showed a complete response, and he has been well without tumor re-growth ever since. The combination of PTX and S-1 not only may be an effective regimen for gastric cancer with liver metastases, but also can be used without side effects for a long time.

The Role of Neoadjuvant Trials in Drug Development for Solid Tumors.

PubMed

Funt, Samuel A; Chapman, Paul B

2016-05-15

The relatively low success rate of phase II oncology trials in predicting success of novel drugs in phase III trials and in gaining regulatory approval may be due to reliance on the endpoint of response rate defined by the RECIST. The neoadjuvant treatment paradigm allows the antitumor activity of a novel therapy to be determined on a pathologic basis at the time of surgery instead of by RECIST, which was not developed to guide clinical decision making or correlate with long-term outcomes. Indeed, the FDA endorsed pathologic complete response (pCR) as a surrogate for overall survival (OS) in early-stage breast cancer and granted accelerated approval to pertuzumab based on this endpoint. We propose that pCR is a biologically rational method of determining treatment effect that may be more likely to predict OS. We discuss some advantages of the neoadjuvant trial design, review the use of neoadjuvant therapy as standards of care, and consider the neoadjuvant platform as a method for drug development. Clin Cancer Res; 22(10); 2323-8. ©2016 AACR. ©2016 American Association for Cancer Research.

Development of Web tools to predict axillary lymph node metastasis and pathological response to neoadjuvant chemotherapy in breast cancer patients.

PubMed

Sugimoto, Masahiro; Takada, Masahiro; Toi, Masakazu

2014-12-09

Nomograms are a standard computational tool to predict the likelihood of an outcome using multiple available patient features. We have developed a more powerful data mining methodology, to predict axillary lymph node (AxLN) metastasis and response to neoadjuvant chemotherapy (NAC) in primary breast cancer patients. We developed websites to use these tools. The tools calculate the probability of AxLN metastasis (AxLN model) and pathological complete response to NAC (NAC model). As a calculation algorithm, we employed a decision tree-based prediction model known as the alternative decision tree (ADTree), which is an analog development of if-then type decision trees. An ensemble technique was used to combine multiple ADTree predictions, resulting in higher generalization abilities and robustness against missing values. The AxLN model was developed with training datasets (n=148) and test datasets (n=143), and validated using an independent cohort (n=174), yielding an area under the receiver operating characteristic curve (AUC) of 0.768. The NAC model was developed and validated with n=150 and n=173 datasets from a randomized controlled trial, yielding an AUC of 0.787. AxLN and NAC models require users to input up to 17 and 16 variables, respectively. These include pathological features, including human epidermal growth factor receptor 2 (HER2) status and imaging findings. Each input variable has an option of "unknown," to facilitate prediction for cases with missing values. The websites developed facilitate the use of these tools, and serve as a database for accumulating new datasets.

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

Wu, J; Gong, G; Cui, Y

Purpose: To predict early pathological response of breast cancer to neoadjuvant chemotherapy (NAC) based on quantitative, multi-region analysis of dynamic contrast enhancement magnetic resonance imaging (DCE-MRI). Methods: In this institution review board-approved study, 35 patients diagnosed with stage II/III breast cancer were retrospectively investigated using DCE-MR images acquired before and after the first cycle of NAC. First, principal component analysis (PCA) was used to reduce the dimensionality of the DCE-MRI data with a high-temporal resolution. We then partitioned the whole tumor into multiple subregions using k-means clustering based on the PCA-defined eigenmaps. Within each tumor subregion, we extracted four quantitativemore » Haralick texture features based on the gray-level co-occurrence matrix (GLCM). The change in texture features in each tumor subregion between pre- and during-NAC was used to predict pathological complete response after NAC. Results: Three tumor subregions were identified through clustering, each with distinct enhancement characteristics. In univariate analysis, all imaging predictors except one extracted from the tumor subregion associated with fast wash-out were statistically significant (p< 0.05) after correcting for multiple testing, with area under the ROC curve or AUCs between 0.75 and 0.80. In multivariate analysis, the proposed imaging predictors achieved an AUC of 0.79 (p = 0.002) in leave-one-out cross validation. This improved upon conventional imaging predictors such as tumor volume (AUC=0.53) and texture features based on whole-tumor analysis (AUC=0.65). Conclusion: The heterogeneity of the tumor subregion associated with fast wash-out on DCE-MRI predicted early pathological response to neoadjuvant chemotherapy in breast cancer.« less

High-dose interleukin2 - a 10-year single-site experience in the treatment of metastatic renal cell carcinoma: careful selection of patients gives an excellent outcome.

PubMed

Chow, S; Galvis, V; Pillai, M; Leach, R; Keene, E; Spencer-Shaw, A; Shablak, A; Shanks, J; Liptrot, T; Thistlethwaite, F; Hawkins, R E

2016-01-01

VEGF-targeted therapy has become the mainstay of treatment for majority of mRCC patients. For most patients, benefit is short-lived and therefore treatment remains palliative in intent. HD IL2 is an effective immunotherapy treatment capable of durable remission in some patients but its unselected use has been difficult due to its modest response rate and considerable adverse effects. Using set pathology criteria as a selection tool in clinical practice, we have been able to show improved outcomes in our previous report. Here, we present an updated and extended report of this treatment and seek to explore any pathological, clinical and treatment variables likely to predict better outcomes. This is an extension of a previously reported clinical audit, which includes mRCC cases treated with HD IL2 between 2003 and 2013. Since 2006, tumour specimens of potential candidates were routinely reviewed prospectively and stratified into Favourable or Other categories based on constitution of histological growth pattern, namely alveolar or solid versus papillary and/or sarcomatoid architecture; clear cell versus granular cell cytoplasmic morphology. HD IL2 was preferentially offered to patients with Favourable pathology. Outcome evaluation includes response rates, survival, and treatment tolerance. Multivariate analysis was performed to explore potential prognostic and predictive factors. Among prospectively selected patients with Favourable pathology ( n  = 106), overall response rate was 48.1 % (51/106) with CR rate of 21.6 % (23/106). Median OS was 58.1 months. Factors associated with significantly better response and/or survival includes favourable pathology pattern, higher cycle 1 tolerance and lower number of metastatic organ sites (<3). CAIX (Carbonic anhydrase 9) has prognostic value but is not predictive of response. Toxicities were those expected of IL2 but were manageable on general medical wards, with no treatment-related death. Importantly most complete responses were durable with 76 % (23/30) cases remained relapse-free (median 39 months follow up) and 2 of the seven who relapsed had had long-term disease free survival after resection of oligometastatic relapse. Our experience shows that HD IL2 remains an effective and safe treatment in well-selected cases of mRCC. The result in this single-institution patient series confirms similar outcomes to our previously reported retrospective series. Given the prospect of long-term remission, fit patients with Favourable histology and low disease burden should be considered for HD IL2 in an experienced centre. Better understanding has been gained from this in-depth analysis especially the examination of possible response predictors and strategies that can improve treatment outcome.

Digital pathology for the primary diagnosis of breast histopathological specimens: an innovative validation and concordance study on digital pathology validation and training.

PubMed

Williams, Bethany Jill; Hanby, Andrew; Millican-Slater, Rebecca; Nijhawan, Anju; Verghese, Eldo; Treanor, Darren

2018-03-01

To train and individually validate a group of breast pathologists in specialty-specific digital primary diagnosis by using a novel protocol endorsed by the Royal College of Pathologists' new guideline for digital pathology. The protocol allows early exposure to live digital reporting, in a risk-mitigated environment, and focuses on patient safety and professional development. Three specialty breast pathologists completed training in the use of a digital microscopy system, and were exposed to a training set of 20 challenging cases, designed to help them identify personal digital diagnostic pitfalls. Following this, the three pathologists viewed a total of 694 live, entire breast cases. All primary diagnoses were made on digital slides, with immediate glass slide review and reconciliation before final case sign-out. There was complete clinical concordance between the glass and digital impression of the case in 98.8% of cases. Only 1.2% of cases had a clinically significant difference in diagnosis/prognosis on glass and digital slide reads. All pathologists elected to continue using the digital microscope as the standard for breast histopathology specimens, with deferral to glass for a limited number of clinical/histological scenarios as a safety net. Individual training and validation for digital primary diagnosis allows pathologists to develop competence and confidence in their digital diagnostic skills, and aids safe and responsible transition from the light microscope to the digital microscope. © 2017 John Wiley & Sons Ltd.

A recombinant anchorless respiratory syncytial virus (RSV) fusion (F) protein/monophosphoryl lipid A (MPL) vaccine protects against RSV-induced replication and lung pathology.

PubMed

Blanco, Jorge C G; Boukhvalova, Marina S; Pletneva, Lioubov M; Shirey, Kari Ann; Vogel, Stefanie N

2014-03-14

We previously demonstrated that the severe cytokine storm and pathology associated with RSV infection following intramuscular vaccination of cotton rats with FI-RSV Lot 100 could be completely abolished by formulating the vaccine with the mild TLR4 agonist and adjuvant, monophosphoryl lipid A (MPL). Despite this significant improvement, the vaccine failed to blunt viral replication in the lungs. Since MPL is a weak TLR4 agonist, we hypothesized that its adjuvant activity was mediated by modulating the innate immune response of respiratory tract resident macrophages. Therefore, we developed a new vaccine preparation with purified, baculovirus expressed, partially purified, anchorless RSV F protein formulated with synthetic MPL that was administered to cotton rats intranasally, followed by an intradermal boost. This novel formulation and heterologous "prime/boost" route of administration resulted in decreased viral titers compared to that seen in animals vaccinated with F protein alone. Furthermore, animals vaccinated by this route showed no evidence of enhanced lung pathology upon RSV infection. This indicates that MPL acts as an immune modulator that protects the host from vaccine-enhanced pathology, and reduces RSV replication in the lower respiratory tract when administered by a heterologous prime/boost immunization regimen. Copyright © 2013 Elsevier Ltd. All rights reserved.

Alcohol effects on the epigenome in the germline: role in the inheritance of alcohol-related pathology

PubMed Central

Chastain, Lucy G.; Sarkar, Dipak K.

2017-01-01

Excessive alcohol exposure has severe health consequences, and clinical and animal studies have demonstrated that disruptions in the epigenome of somatic cells, such as those in brain, are an important factor in the development of alcohol-related pathologies, such as alcohol-use disorders (AUDs) and fetal alcohol spectrum disorders (FASDs). It is also well known that alcohol-related health problems are passed down across generations in human populations, but the complete mechanisms for this phenomenon are currently unknown. Recent studies in animal models have suggested that epigenetic factors are also responsible for the transmission of alcohol-related pathologies across generations. Alcohol exposure has been shown to induce changes in the epigenome of sperm of exposed male animals, and these epimutations are inherited in the offspring. This paper reviews evidence for multigenerational and transgenerational epigenetic inheritance of alcohol-related pathology through the germline. We also review the literature on the epigenetic effects of alcohol exposure on somatic cells in brain, and its contribution to AUDs and FASDs. We note gaps in knowledge in this field, such as the lack of clinical studies in human populations and the lack of data on epigenetic inheritance via the female germline, and we suggest future research directions. PMID:28431793

Phase II Study of Neoadjuvant Anthracycline-Based Regimens Combined With Nanoparticle Albumin-Bound Paclitaxel and Trastuzumab for Human Epidermal Growth Factor Receptor 2-Positive Operable Breast Cancer.

PubMed

Tanaka, Satoru; Iwamoto, Mitsuhiko; Kimura, Kosei; Matsunami, Nobuki; Morishima, Hirotaka; Yoshidome, Katsuhide; Nomura, Takashi; Morimoto, Takashi; Yamamoto, Daigo; Tsubota, Yu; Kobayashi, Toshihiro; Uchiyama, Kazuhisa

2015-06-01

We treated patients with operable human epidermal growth factor receptor 2-positive breast cancer with neoadjuvant anthracycline regimens followed by nanoparticle albumin-bound paclitaxel plus trastuzumab. Of the 44 patients, 49% achieved a pathologic complete response (pCR). The pCR rate was 36% and 71% in the patients with estrogen receptor-positive and -negative cancer, respectively. Neoadjuvant therapy using this combination appears to be effective and safe. Introduction: Neoadjuvant chemotherapy plus trastuzumab. Neoadjuvant chemotherapy plus trastuzumab results in a 30% to 50% pathologic complete response (pCR) rate in human epidermal growth factor receptor 2 (HER2)-positive breast cancer and has been associated with improved therapeutic outcomes. Thus, the pCR rate can be useful in evaluating novel agents in this patient population. Nanoparticle albumin-bound (nab)-paclitaxel (PTX) can reduce the toxicity of PTX while maintaining its efficacy. The present study evaluated the activity and safety of nab-PTX as a neoadjuvant treatment of HER2(+) breast cancer. We treated patients with stage I to IIIA breast cancer using neoadjuvant epirubicin/cyclophosphamide (EC) or 5-fluorouracil/epirubicin/cyclophosphamide every 3 weeks (q3w) for 4 cycles, followed by nab-PTX (260 mg/m(2)) plus trastuzumab q3w for 4 cycles. The primary endpoint was the pCR rate. The secondary endpoints included the clinical response rate, disease-free survival, pathologic response rate (defined as pCR or minimal residual invasive disease only in the breast), breast-conserving surgery rate, and safety. Forty-six patients were enrolled. One patient met the exclusion criteria because of the coexistence of another malignant disease; therefore, we evaluated 45 patients in the entire study. One patient experienced rapid disease progression during EC therapy, leaving 44 patients evaluable for nab-PTX treatment. Of the 45 patients, 49% achieved a pCR. The pCR rate was 36% and 71% in those with estrogen receptor-positive and -negative cancer, respectively. Of all the study treatments, the most frequent reason for delay or dose reduction was hematologic toxicity; only 1 patient required a dose reduction for nab-PTX because of peripheral neuropathy. Neoadjuvant therapy using this combination appears to be effective and safe. Copyright © 2015 Elsevier Inc. All rights reserved.

[Application of decision curve on evaluation of MRI predictive model for early assessing pathological complete response to neoadjuvant therapy in breast cancer].

PubMed

He, Y J; Li, X T; Fan, Z Q; Li, Y L; Cao, K; Sun, Y S; Ouyang, T

2018-01-23

Objective: To construct a dynamic enhanced MR based predictive model for early assessing pathological complete response (pCR) to neoadjuvant therapy in breast cancer, and to evaluate the clinical benefit of the model by using decision curve. Methods: From December 2005 to December 2007, 170 patients with breast cancer treated with neoadjuvant therapy were identified and their MR images before neoadjuvant therapy and at the end of the first cycle of neoadjuvant therapy were collected. Logistic regression model was used to detect independent factors for predicting pCR and construct the predictive model accordingly, then receiver operating characteristic (ROC) curve and decision curve were used to evaluate the predictive model. Results: ΔArea(max) and Δslope(max) were independent predictive factors for pCR, OR =0.942 (95% CI : 0.918-0.967) and 0.961 (95% CI : 0.940-0.987), respectively. The area under ROC curve (AUC) for the constructed model was 0.886 (95% CI : 0.820-0.951). Decision curve showed that in the range of the threshold probability above 0.4, the predictive model presented increased net benefit as the threshold probability increased. Conclusions: The constructed predictive model for pCR is of potential clinical value, with an AUC>0.85. Meanwhile, decision curve analysis indicates the constructed predictive model has net benefit from 3 to 8 percent in the likely range of probability threshold from 80% to 90%.

Prospective validation of pathologic complete response models in rectal cancer: Transferability and reproducibility.

PubMed

van Soest, Johan; Meldolesi, Elisa; van Stiphout, Ruud; Gatta, Roberto; Damiani, Andrea; Valentini, Vincenzo; Lambin, Philippe; Dekker, Andre

2017-09-01

Multiple models have been developed to predict pathologic complete response (pCR) in locally advanced rectal cancer patients. Unfortunately, validation of these models normally omit the implications of cohort differences on prediction model performance. In this work, we will perform a prospective validation of three pCR models, including information whether this validation will target transferability or reproducibility (cohort differences) of the given models. We applied a novel methodology, the cohort differences model, to predict whether a patient belongs to the training or to the validation cohort. If the cohort differences model performs well, it would suggest a large difference in cohort characteristics meaning we would validate the transferability of the model rather than reproducibility. We tested our method in a prospective validation of three existing models for pCR prediction in 154 patients. Our results showed a large difference between training and validation cohort for one of the three tested models [Area under the Receiver Operating Curve (AUC) cohort differences model: 0.85], signaling the validation leans towards transferability. Two out of three models had a lower AUC for validation (0.66 and 0.58), one model showed a higher AUC in the validation cohort (0.70). We have successfully applied a new methodology in the validation of three prediction models, which allows us to indicate if a validation targeted transferability (large differences between training/validation cohort) or reproducibility (small cohort differences). © 2017 American Association of Physicists in Medicine.

Treatment outcomes regarding the addition of targeted agents in the therapeutic portfolio for stage II-III rectal cancer undergoing neoadjuvant chemoradiation.

PubMed

Liang, Jin-Tung; Chen, Tzu-Chun; Huang, John; Jeng, Yung-Ming; Cheng, Jason Chia-Hsien

2017-11-24

To evaluate the impact of targeted agents in stage II-III rectal cancer undergoing neoadjuvant concurrent chemoradiation therapy (CCRT). A retrospective study was performed in 124 consecutive patients with clinically T 3 N 0-2 M 0 -staged rectal cancer incorporating targeted agents in CCRT. Pathologic complete response was detected in 34.2% (n=26) of bevacizumab+FOLFOX-treated patients (n=76), which was significantly higher (p=0.019, post-hoc statistical power =35.87%) than that (n=10, 20.8%) of the cetuximab+FOLFOX-treated patients (n=48). Patients receiving cetuximab+FOLFOX therapy tended to develop severe liver toxicity (91.7%, n=44 versus 17.1%, n=13, p<0.0001), as evaluated by morphologic grading of hepatic steatosis and sinusoidal dilatation in laparoscopy. In the 57 patients with morphologically severe liver toxicity, 36 (63.2%) retained a normal liver function; for the remaining 21 patients with an abnormal liver function, the abnormality was self-limited in 19 patients, whereas 2 cetuximab-treated patients progressed to hepatic failure and mortality. A subset analysis within bevacizumab+FOLFOX-treated patients with either wild-type (n=36) or mutant (n=40) K-ras status indicated K-ras status did not significantly influence the treatment outcomes. The addition of bevacizumab instead of cetuximab to FOLFOX in the neoadjuvant settings for T 3 N 0-2 M 0 -staged rectal cancer could induce a promising rate of pathologic complete response and lesser hepatotoxicity.

Neoadjuvant chemoradiation therapy and pathological complete response in rectal cancer

PubMed Central

Ferrari, Linda; Fichera, Alessandro

2015-01-01

The management of rectal cancer has evolved significantly in the last few decades. Significant improvements in local disease control were achieved in the 1990s, with the introduction of total mesorectal excision and neoadjuvant radiotherapy. Level 1 evidence has shown that, with neoadjuvant chemoradiation therapy (CRT) the rates of local recurrence can be lower than 6% and, as a result, neoadjuvant CRT currently represents the accepted standard of care. This approach has led to reliable tumor down-staging, with 15–27% patients with a pathological complete response (pCR)—defined as no residual cancer found on histological examination of the specimen. Patients who achieve pCR after CRT have better long-term outcomes, less risk of developing local or distal recurrence and improved survival. For all these reasons, sphincter-preserving procedures or organ-preserving options have been suggested, such as local excision of residual tumor or the omission of surgery altogether. Although local recurrence rate has been stable at 5–6% with this multidisciplinary management method, distal recurrence rates for locally-advanced rectal cancers remain in excess of 25% and represent the main cause of death in these patients. For this reason, more recent trials have been looking at the administration of full-dose systemic chemotherapy in the neoadjuvant setting (in order to offer early treatment of disseminated micrometastases, thus improving control of systemic disease) and selective use of radiotherapy only in non-responders or for low rectal tumors smaller than 5 cm. PMID:26290512

Individual Differences in Typical Reappraisal Use Predict Amygdala and Prefrontal Responses

PubMed Central

Drabant, Emily M.; McRae, Kateri; Manuck, Stephen B.; Hariri, Ahmad R.; Gross, James J.

2010-01-01

Background Participants who are instructed to use reappraisal to downregulate negative emotion show decreased amygdala responses and increased prefrontal responses. However, it is not known whether individual differences in the tendency to use reappraisal manifests in similar neural responses when individuals are spontaneously confronted with negative situations. Such spontaneous emotion regulation might play an important role in normal and pathological responses to the emotional challenges of everyday life. Methods Fifty-six healthy women completed a blood oxygenation-level dependent functional magnetic resonance imaging challenge paradigm involving the perceptual processing of emotionally negative facial expressions. Participants also completed measures of typical emotion regulation use, trait anxiety, and neuroticism. Results Greater use of reappraisal in everyday life was related to decreased amygdala activity and increased prefrontal and parietal activity during the processing of negative emotional facial expressions. These associations were not attributable to variation in trait anxiety, neuroticism, or the use of another common form of emotion regulation, namely suppression. Conclusions These findings suggest that, like instructed reappraisal, individual differences in reappraisal use are associated with decreased activation in ventral emotion generative regions and increased activation in prefrontal control regions in response to negative stimuli. Such individual differences in emotion regulation might predict successful coping with emotional challenges as well as the onset of affective disorders. PMID:18930182

Digital gene expression profiling analysis and its application in the identification of genes associated with improved response to neoadjuvant chemotherapy in breast cancer.

PubMed

Liu, Xiaozhen; Jin, Gan; Qian, Jiacheng; Yang, Hongjian; Tang, Hongchao; Meng, Xuli; Li, Yongfeng

2018-04-23

This study aimed to screen sensitive biomarkers for the efficacy evaluation of neoadjuvant chemotherapy in breast cancer. In this study, Illumina digital gene expression sequencing technology was applied and differentially expressed genes (DEGs) between patients presenting pathological complete response (pCR) and non-pathological complete response (NpCR) were identified. Further, gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were then performed. The genes in significant enriched pathways were finally quantified by quantitative real-time PCR (qRT-PCR) to confirm that they were differentially expressed. Additionally, GSE23988 from Gene Expression Omnibus database was used as the validation dataset to confirm the DEGs. After removing the low-quality reads, 715 DEGs were finally detected. After mapping to KEGG pathways, 10 DEGs belonging to the ubiquitin proteasome pathway (HECTD3, PSMB10, UBD, UBE2C, and UBE2S) and cytokine-cytokine receptor interactions (CCL2, CCR1, CXCL10, CXCL11, and IL2RG) were selected for further analysis. These 10 genes were finally quantified by qRT-PCR to confirm that they were differentially expressed (the log 2 fold changes of selected genes were - 5.34, 7.81, 6.88, 5.74, 3.11, 19.58, 8.73, 8.88, 7.42, and 34.61 for HECTD3, PSMB10, UBD, UBE2C, UBE2S, CCL2, CCR1, CXCL10, CXCL11, and IL2RG, respectively). Moreover, 53 common genes were confirmed by the validation dataset, including downregulated UBE2C and UBE2S. Our results suggested that these 10 genes belonging to these two pathways might be useful as sensitive biomarkers for the efficacy evaluation of neoadjuvant chemotherapy in breast cancer.

Impact of Race, Ethnicity and BMI on Achievement of Pathologic Complete Response Following Neoadjuvant Chemotherapy for Breast Cancer: A Pooled Analysis of Four Prospective Alliance Clinical Trials (A151426)

PubMed Central

Warner, Erica T.; Ballman, Karla V.; Strand, Carrie; Boughey, Judy; Buzdar, Aman U.; Carey, Lisa A.; Sikov, William M.; Partridge, H.

2016-01-01

Purpose Previous studies demonstrated poor response to neoadjuvant systemic therapy (NST) for breast cancer among black women and women who are overweight or obese but this may be due to chemotherapy under dosing. We assessed associations of race, ethnicity and body mass index (BMI) with pathologic complete response (pCR) in clinical trial populations. Methods 1797 women enrolled in four NST trials (CALGB 40601, 40603; ACOSOG Z1041, Z1071) were included. Tumor subtypes were defined by estrogen receptor (ER) and HER2 status. Logistic regression generated odds ratios (OR) and 95% confidence intervals (CI) for the associations of race, ethnicity, and BMI with pCR adjusting for subtype, study arm, lymph node status, tumor size, and tumor grade. Results 253 (14.1%) were black, 199 (11.1%) Hispanic, 520 (28.9%) overweight, and 743 (41.4%) obese. Compared to whites, Blacks and Hispanics were more likely to be obese and Blacks were more likely to have triple-negative cancer. pCR rates differed significantly by tumor subtype. In multivariate analyses, neither race (black vs. white: OR: 1.18, 95% CI: 0.85–1.62) nor ethnicity (Hispanic vs. non-Hispanic: OR: 1.30, 95% CI: 0.67–2.53) were significant predictors of pCR overall or by subtype. Overweight and obese women had lower pCR rates in ER+/HER2+, but higher pCR rates in ER−/HER2+ cancers. Conclusions There was no difference in breast pCR according to race or ethnicity. Overall, there was no major difference in pCR rates by BMI. These findings suggest that pCR with optimally dosed NST is a function of tumor, rather than patient, biology. PMID:27449492

Impact of race, ethnicity, and BMI on achievement of pathologic complete response following neoadjuvant chemotherapy for breast cancer: a pooled analysis of four prospective Alliance clinical trials (A151426).

PubMed

Warner, Erica T; Ballman, Karla V; Strand, Carrie; Boughey, Judy C; Buzdar, Aman U; Carey, Lisa A; Sikov, William M; Partridge, Ann H

2016-08-01

Previous studies demonstrated poor response to neoadjuvant systemic therapy (NST) for breast cancer among black women and women who are overweight or obese, but this may be due to chemotherapy underdosing. We assessed associations of race, ethnicity, and body mass index (BMI) with pathologic complete response (pCR) in clinical trial populations. 1797 women enrolled in four NST trials (CALGB 40601, 40603; ACOSOG Z1041, Z1071) were included. Tumor subtypes were defined by estrogen receptor (ER) and HER2 status. Logistic regression generated odds ratios (OR) and 95 % confidence intervals (CI) for the associations of race, ethnicity, and BMI with in-breast pCR adjusting for subtype, study arm, lymph node status, tumor size, and tumor grade. 253 (14.1 %) were black, 199 (11.1 %) Hispanic, 520 (28.9 %) overweight, and 743 (41.4 %) obese. Compared to whites, Blacks and Hispanics were more likely to be obese and Blacks were more likely to have triple-negative cancer. pCR rates differed significantly by tumor subtype. In multivariate analyses, neither race (black vs white: OR 1.18, 95 % CI 0.85-1.62) nor ethnicity (Hispanic vs non-Hispanic; OR 1.30, 95 % CI 0.67-2.53) were significant predictors of pCR overall or by subtype. Overweight and obese women had lower pCR rates in ER+/HER2+, but higher pCR rates in ER-/HER2+ cancers. There was no difference in pCR according to race or ethnicity. Overall, there was no major difference in pCR rates by BMI. These findings suggest that pCR with optimally dosed NST is a function of tumor, rather than patient, biology.

Circulating Tumor Cells in Breast Cancer Patients Treated by Neoadjuvant Chemotherapy: A Meta-analysis.

PubMed

Bidard, François-Clément; Michiels, Stefan; Riethdorf, Sabine; Mueller, Volkmar; Esserman, Laura J; Lucci, Anthony; Naume, Bjørn; Horiguchi, Jun; Gisbert-Criado, Rafael; Sleijfer, Stefan; Toi, Masakazu; Garcia-Saenz, Jose A; Hartkopf, Andreas; Generali, Daniele; Rothé, Françoise; Smerage, Jeffrey; Muinelo-Romay, Laura; Stebbing, Justin; Viens, Patrice; Magbanua, Mark Jesus M; Hall, Carolyn S; Engebraaten, Olav; Takata, Daisuke; Vidal-Martínez, José; Onstenk, Wendy; Fujisawa, Noriyoshi; Diaz-Rubio, Eduardo; Taran, Florin-Andrei; Cappelletti, Maria Rosa; Ignatiadis, Michail; Proudhon, Charlotte; Wolf, Denise M; Bauldry, Jessica B; Borgen, Elin; Nagaoka, Rin; Carañana, Vicente; Kraan, Jaco; Maestro, Marisa; Brucker, Sara Yvonne; Weber, Karsten; Reyal, Fabien; Amara, Dominic; Karhade, Mandar G; Mathiesen, Randi R; Tokiniwa, Hideaki; Llombart-Cussac, Antonio; Meddis, Alessandra; Blanche, Paul; d'Hollander, Koenraad; Cottu, Paul; Park, John W; Loibl, Sibylle; Latouche, Aurélien; Pierga, Jean-Yves; Pantel, Klaus

2018-04-12

We conducted a meta-analysis in nonmetastatic breast cancer patients treated by neoadjuvant chemotherapy (NCT) to assess the clinical validity of circulating tumor cell (CTC) detection as a prognostic marker. We collected individual patient data from 21 studies in which CTC detection by CellSearch was performed in early breast cancer patients treated with NCT. The primary end point was overall survival, analyzed according to CTC detection, using Cox regression models stratified by study. Secondary end points included distant disease-free survival, locoregional relapse-free interval, and pathological complete response. All statistical tests were two-sided. Data from patients were collected before NCT (n = 1574) and before surgery (n = 1200). CTC detection revealed one or more CTCs in 25.2% of patients before NCT; this was associated with tumor size (P < .001). The number of CTCs detected had a detrimental and decremental impact on overall survival (P < .001), distant disease-free survival (P < .001), and locoregional relapse-free interval (P < .001), but not on pathological complete response. Patients with one, two, three to four, and five or more CTCs before NCT displayed hazard ratios of death of 1.09 (95% confidence interval [CI] = 0.65 to 1.69), 2.63 (95% CI = 1.42 to 4.54), 3.83 (95% CI = 2.08 to 6.66), and 6.25 (95% CI = 4.34 to 9.09), respectively. In 861 patients with full data available, adding CTC detection before NCT increased the prognostic ability of multivariable prognostic models for overall survival (P < .001), distant disease-free survival (P < .001), and locoregional relapse-free interval (P = .008). CTC count is an independent and quantitative prognostic factor in early breast cancer patients treated by NCT. It complements current prognostic models based on tumor characteristics and response to therapy.

Predictive factors of pathologic complete response of HER2-positive breast cancer after preoperative chemotherapy with trastuzumab: development of a specific predictor and study of its utilities using decision curve analysis.

PubMed

Jankowski, Clémentine; Guiu, S; Cortet, M; Charon-Barra, C; Desmoulins, I; Lorgis, V; Arnould, L; Fumoleau, P; Coudert, B; Rouzier, R; Coutant, C; Reyal, F

2017-01-01

The aim of this study was to assess the Institut Gustave Roussy/M.D. Anderson Cancer Center (IGR/MDACC) nomogram in predicting pathologic complete response (pCR) to preoperative chemotherapy in a cohort of human epidermal growth factor receptor 2 (HER2)-positive tumors treated with preoperative chemotherapy with trastuzumab. We then combine clinical and pathological variables associated with pCR into a new nomogram specific to HER2-positive tumors treated by preoperative chemotherapy with trastuzumab. Data from 270 patients with HER2-positive tumors treated with preoperative chemotherapy with trastuzumab at the Institut Curie and at the Georges François Leclerc Cancer Center were used to assess the IGR/MDACC nomogram and to subsequently develop a new nomogram for pCR based on multivariate logistic regression. Model performance was quantified in terms of calibration and discrimination. We studied the utility of the new nomogram using decision curve analysis. The IGR/MDACC nomogram was not accurate for the prediction of pCR in HER2-positive tumors treated by preoperative chemotherapy with trastuzumab, with poor discrimination (AUC = 0.54, 95% CI 0.51-0.58) and poor calibration (p = 0.01). After uni- and multivariate analysis, a new pCR nomogram was built based on T stage (TNM), hormone receptor status, and Ki67 (%). The model had good discrimination with an area under the curve (AUC) at 0.74 (95% CI 0.70-0.79) and adequate calibration (p = 0.93). By decision curve analysis, the model was shown to be relevant between thresholds of 0.3 and 0.7. To the best of our knowledge, ours is the first nomogram to predict pCR in HER2-positive tumors treated by preoperative chemotherapy with trastuzumab. To ensure generalizability, this model needs to be externally validated.

Impact of sarcopenia on outcomes of locally advanced esophageal cancer patients treated with neoadjuvant chemoradiation followed by surgery

PubMed Central

Venkat, Puja S.; Jin, William; Leuthold, Susan; Latifi, Kujtim; Almhanna, Khaldoun; Pimiento, Jose M.; Fontaine, Jacques-Pierre; Hoffe, Sarah E.; Frakes, Jessica M.

2017-01-01

Background Sarcopenia is an independent predictor of clinical outcomes in multiple gastrointestinal cancers. Total psoas area (TPA), as measured on a single cross-sectional CT image at the L4 vertebral body level, has been correlated with sarcopenia. We sought to evaluate whether TPA was predictive of acute grade ≥3 toxicity, pathologic response, and overall survival in patients with locally advanced esophageal cancer receiving tri-modality therapy. Methods An institutional database of esophageal cancer patients treated with neoadjuvant chemoradiation followed by surgery was queried. Of 77 patients treated from 2008 to 2012 with intensity modulated radiation therapy (IMRT) and image guided radiation therapy (IGRT), 56 patients were eligible based on having CT imaging that included the L4 vertebral body. The L4 vertebra was identified on axial CT and the psoas muscle was manually contoured bilaterally to determine the skeletal muscle index. Sarcopenia was defined by the presence of the psoas area less than the median of the cohort. Acute toxicity was defined as within 3 months of radiotherapy based on Common Terminology Criteria for Adverse Events. ROC curve, logistic regression, and Kaplan Meier estimates were used when appropriate. Results Sarcopenia was associated with increased acute grade ≥3 toxicity from chemoradiation by ROC analysis using a cut off of 841.5 mm2/m2 (P=0.003, AUC 0.709, sensitivity 60.9%, specificity 78.8%) and logistic regression (P=0.002). Patients with TPA <841.5 mm2/m2 were 5.78 times more likely to develop grade 3 or higher toxicity (P=0.004). Sarcopenia did not predict a difference in overall survival (P=0.217) and was not significant for pathologic complete response or favorable pathologic response (TRG 0/1). Conclusions In our cohort of patients, sarcopenia was associated with a significant increase in acute grade ≥3 toxicity with chemoradiation, suggesting a potential role for neoadjuvant patient selection strategies. There was no difference in pathologic response or overall survival. PMID:29184684

Phase II Study of Neoadjuvant Bevacizumab and Radiotherapy for Resectable Soft Tissue Sarcomas

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

Yoon, Sam S., E-mail: syoon@partners.org; Department of Cancer Biology, University of Pennsylvania School of Medicine, Philadelphia, PA; Duda, Dan G.

Purpose: Numerous preclinical studies have demonstrated that angiogenesis inhibitors can increase the efficacy of radiotherapy (RT). We sought to examine the safety and efficacy of bevacizumab (BV) and RT in soft tissue sarcomas and explore biomarkers to help determine the treatment response. Methods and Materials: Patients with {>=}5 cm, intermediate- or high-grade soft tissue sarcomas at significant risk of local recurrence received neoadjuvant BV alone followed by BV plus RT before surgical resection. Correlative science studies included analysis of the serial blood and tumor samples and serial perfusion computed tomography scans. Results: The 20 patients had a median tumor sizemore » of 8.25 cm, with 13 extremity, 1 trunk, and 6 retroperitoneal/pelvis tumors. The neoadjuvant treatment was well tolerated, with only 4 patients having Grade 3 toxicities (hypertension, liver function test elevation). BV plus RT resulted in {>=}80% pathologic necrosis in 9 (45%) of 20 tumors, more than double the historical rate seen with RT alone. Three patients had a complete pathologic response. The median microvessel density decreased 53% after BV alone (p <.05). After combination therapy, the median tumor cell proliferation decreased by 73%, apoptosis increased 10.4-fold, and the blood flow, blood volume, and permeability surface area decreased by 62-72% (p <.05). Analysis of gene expression microarrays of untreated tumors identified a 24-gene signature for treatment response. The microvessel density and circulating progenitor cells at baseline and the reduction in microvessel density and plasma soluble c-KIT with BV therapy also correlated with a good pathologic response (p <.05). After a median follow-up of 20 months, only 1 patient had developed local recurrence. Conclusions: The results from the present exploratory study indicated that BV increases the efficacy of RT against soft tissue sarcomas and might reduce the incidence of local recurrence. Thus, this regimen warrants additional investigation. Gene expression profiles and other tissue and circulating biomarkers showed promising correlations with treatment response.« less

The role of exercise dependence for the relationship between exercise behavior and eating pathology: mediator or moderator?

PubMed

Cook, Brian J; Hausenblas, Heather A

2008-05-01

Our study examined the potential mediating or moderating effect of exercise dependence on the exercise-eating pathology relationship. Female university students (N = 330) completed Internet-based self-report measures of exercise behavior, exercise dependence, and eating pathology. Exercise dependence served as a mediator for the relationship between exercise and eating pathology. This unidirectional causal model suggests that an individual's pathological motivation or compulsion to exercise is the critical mediating component in the exercise-eating pathology relationship. The best target for removing the link between exercise behavior and eating pathology may be reformulating exercise dependence symptoms.

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

Perez, Rodrigo O.; Angelita and Joaquim Gama Institute, Sao Paulo; Habr-Gama, Angelita, E-mail: gamange@uol.com.br

Purpose: To estimate the metabolic activity of rectal cancers at 6 and 12 weeks after completion of chemoradiation therapy (CRT) by 2-[fluorine-18] fluoro-2-deoxy-D-glucose-labeled positron emission tomography/computed tomography ([{sup 18}FDG]PET/CT) imaging and correlate with response to CRT. Methods and Materials: Patients with cT2-4N0-2M0 distal rectal adenocarcinoma treated with long-course neoadjuvant CRT (54 Gy, 5-fluouracil-based) were prospectively studied ( (ClinicalTrials.org) identifier (NCT00254683)). All patients underwent 3 PET/CT studies (at baseline and 6 and 12 weeks from CRT completion). Clinical assessment was at 12 weeks. Maximal standard uptake value (SUVmax) of the primary tumor was measured and recorded at each PET/CT study aftermore » 1 h (early) and 3 h (late) from {sup 18}FDG injection. Patients with an increase in early SUVmax between 6 and 12 weeks were considered 'bad' responders and the others as 'good' responders. Results: Ninety-one patients were included; 46 patients (51%) were 'bad' responders, whereas 45 (49%) patients were 'good' responders. 'Bad' responders were less likely to develop complete clinical response (6.5% vs. 37.8%, respectively; P=.001), less likely to develop significant histological tumor regression (complete or near-complete pathological response; 16% vs. 45%, respectively; P=.008) and exhibited greater final tumor dimension (4.3 cm vs. 3.3 cm; P=.03). Decrease between early (1 h) and late (3 h) SUVmax at 6-week PET/CT was a significant predictor of 'good' response (accuracy of 67%). Conclusions: Patients who developed an increase in SUVmax after 6 weeks were less likely to develop significant tumor downstaging. Early-late SUVmax variation at 6-week PET/CT may help identify these patients and allow tailored selection of CRT-surgery intervals for individual patients.« less

Duodenal Bulb Adenocarcinoma Benefitted from Neoadjuvant Chemotherapy: A Case Report.

PubMed

Zhang, Geng-Yuan; Mao, Jie; Zhao, Bin; Long, Bo; Zhan, Hao; Zhang, Jun-Qiang; Zhou, Hui-Nian; Guo, Ling-Yun; Jiao, Zuo-Yi

2017-01-01

Duodenal bulb adenocarcinoma is an extremely rare malignancy in the alimentary tract which has a low incidence rate and nonspecific symptoms. It is difficult to diagnose early, and the misdiagnosis rate is high. CT, MRI, upper gastrointestinal endoscopy, and other advanced imaging modalities should be combined to make a comprehensive evaluation. The diagnostic confirmation of this tumor type mainly depends on the pathological examination. The combination of surgery with other treatment modalities is effective. A review of reports on duodenal bulb adenocarcinoma with chemotherapy revealed 6 cases since 1990. However, there are few reports on neoadjuvant chemotherapy for the disease. In this report, preoperative S-1 in combination with oxaliplatin neoadjuvant chemotherapy achieved a complete pathological response in the treatment of duodenal bulb adenocarcinoma. Neoadjuvant chemotherapy shows a better clinical efficacy in the treatment of duodenal bulb adenocarcinoma, but its value needs to be further verified. © 2017 S. Karger AG, Basel.

Primary esophageal mucosa-associated lymphoid tissue lymphoma diagnosed by using stacked forceps biopsy.

PubMed

Lee, D S; Ahn, Y C; Eom, D W; Lee, S J

2016-10-01

Non-Hodgkin lymphoma involving the esophagus is very rare. Only a few cases have been reported in the English literature to date, and it accounts for less than 1% of all cases of gastrointestinal lymphoma. As this malignancy manifests as a submucosal tumor, pathological diagnosis by using a simple endoscopic biopsy alone is difficult. Therefore, surgical biopsy, endoscopic mucosal resection, and endoscopic ultrasound-guided fine-needle aspiration have been used in most cases. Herein, we report a case of esophageal mucosa-associated lymphoid tissue lymphoma in a 49-year-old man, which involved the use of a stacked forceps biopsy to obtain adequate samples for pathological analysis; the use of the stacked forceps biopsy method is unlike those used in previous cases. The patient received cyclophosphamide, vincristine, and prednisolone chemotherapy; he achieved a complete response. In addition, we review the literature relevant to this case. © 2015 International Society for Diseases of the Esophagus.

Barium enema and CT volumetry for predicting pathologic response to preoperative chemoradiotherapy in rectal cancer patients.

PubMed

Murono, Koji; Kawai, Kazushige; Tsuno, Nelson H; Ishihara, Soichiro; Yamaguchi, Hironori; Sunami, Eiji; Kitayama, Joji; Watanabe, Toshiaki

2014-06-01

Preoperative chemoradiotherapy has been widely used for the prevention of local recurrence of locally advanced rectal cancer, and the effect of chemoradiotherapy is known to be associated with overall survival. We aimed to evaluate the association of the pathologic response grade with tumor recurrence rate after chemoradiotherapy, using radiographic analysis and the Response Evaluation Criteria in Solid Tumors as the parameters. This study was conducted at a single tertiary care institution in Japan. This was a retrospective cohort study of patients undergoing preoperative chemoradiotherapy. A total of 101 low rectal cancer patients receiving preoperative chemoradiotherapy from July 2004 to August 2012 were enrolled. The tumor reduction rate was measured with the use of traditional Response Evaluation Criteria in Solid Tumors, barium enema, and CT volumetry, and the correlation between the reduction rate and the pathologic response grade was examined. The tumor reduction rate assessed according to Response Evaluation Criteria in Solid Tumors showed no association with the pathologic response grade (p =0.61). In contrast, the radiographic response rate by both barium enema and CT volumetry strongly correlated with the pathologic response grade (p < 0.0001 and p = 0.001).In terms of local tumor recurrence, those diagnosed as high responders by the pathologic response grade, Response Evaluation Criteria in Solid Tumors, barium enema, and CT volumetry had a lower recurrence rate (p =0.03, p =0.03, p =0.0002, and p =0.001). The difference between high responders and low responders was especially prominent by barium enema and CT volumetry. The study is limited by its retrospective nature. Double-contrast barium enema and CT volumetry were superior to Response Evaluation Criteria in Solid Tumors in evaluating the effect of chemoradiotherapy and predicting the likelihood of tumor recurrence.

Oxaliplatin Plus Dual Inhibition of Thymidilate Synthase During Preoperative Pelvic Radiotherapy for Locally Advanced Rectal Carcinoma: Long-Term Outcome

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

Avallone, Antonio, E-mail: avalloneantonio@libero.i; Delrio, Paolo; Pecori, Biagio

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);more » 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.« less

Treating and Downstaging Hepatocellular Carcinoma in the Caudate Lobe with Yttrium-90 Radioembolization

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

Ibrahim, Saad M.; Kulik, Laura; Baker, Talia

2012-10-15

Purpose: This study was designed to determine the technical feasibility, safety, efficacy, and potential to downstage patients to within transplantation criteria when treating patients with hepatocellular carcinoma (HCC) of the caudate lobe using Y90 radioembolization. Methods: During a 4-year period, 8 of 291 patients treated with radioembolization for unresectable HCC had disease involving the caudate lobe. All patients were followed for treatment-related clinical/biochemical toxicities, serum tumor marker response, and treatment response. Imaging response was assessed with the World Health Organization (WHO) and European Association for the Study of the Liver (EASL) classification schemes. Pathologic response was reported as percent necrosismore » at explantation. Results: Caudate lobe radioembolization was successfully performed in all eight patients. All patients presented with both cirrhosis and portal hypertension. Half were United Network for Organ Sharing (UNOS) stage T3 (n = 4, 50%). Fatigue was reported in half of the patients (n = 4, 50%). One (13%) grade 3/4 bilirubin toxicity was reported. One patient (13%) showed complete tumor response by WHO criteria, and three patients (38%) showed complete response using EASL guidelines. Serum AFP decreased by more than 50% in most patients (n = 6, 75%). Four patients (50%) were UNOS downstaged from T3 to T2, three of who underwent transplantation. One specimen showed histopathologic evidence of 100% complete necrosis, and two specimens demonstrated greater than 50% necrosis. Conclusions: Radioembolization with yttrium-90 appears to be a feasible, safe, and effective treatment option for patients with unresectable caudate lobe HCC. It has the potential to downstage patients to transplantation.« less

Changes in eating pathology and associated symptoms among chronically ill adults attending a brief psychoeducational group.

PubMed

von Ranson, Kristin M; Stevenson, Andrea S; Cannon, Colleen K; Shah, Wendy

2010-08-01

Two quasi-experimental pilot studies examined eating pathology, eating self-efficacy, shame, guilt, and pride in adults with chronic illness before and after participating in brief cognitive-behavioral psychoeducational groups addressing eating concerns. In Study 1, 60 adults completed assessments before and after a series of two groups; in Study 2, 21 adults also completed an assessment five weeks prior to the first group to identify time-related changes in symptoms. Study 1 participants improved across domains, whereas Study 2 analyses also examining time-related changes showed improvements in eating self-efficacy, shame, guilt, and pride, but not in eating pathology. Psychoeducational groups may help improve symptoms including eating pathology, eating self-efficacy, shame, guilt, and pride among chronically-ill adults with eating concerns. 2009 Elsevier Ltd. All rights reserved.

Parent Feeding Behavior and Child Appetite: Associations Depend on Feeding Style

PubMed Central

Carnell, Susan; Benson, Leora; Driggin, Elissa; Kolbe, Laura

2014-01-01

Objective Eating behavior traits measured in early life predict eating behavior and weight trajectories later in development, and may be associated with certain parental feeding behaviors. Our goal was to investigate the relationship between a range of feeding behaviors, and preschoolers’ appetitive traits. Method Four hundred thirty-nine parents of UK 3–5 year olds completed scales measuring authoritarian vs. authoritative forms of limiting (Restriction vs. Monitoring) and promoting (Pressuring vs. Prompting) intake, as well as Emotional and Instrumental Feeding. Parents also completed scales measuring child Food responsiveness and Satiety responsiveness. Child BMI z-scores were calculated based on measured heights and weights. Results Parental Restriction was significantly associated with greater child Food responsiveness (p <.001), but parental Monitoring was not. Parental Pressuring was significantly associated with greater child Satiety responsiveness (p <.001), while parental Prompting was not. Parental Instrumental and Emotional feeding were both associated with greater child Food responsiveness (p <.001). All relationships were independent of child BMI z-score. Discussion Prospective data are needed to determine whether the parent–child feeding relationships identified here promote, or protect against, the development of eating pathology in children. However, our results suggest that cross-sectional associations depend on the style (e.g., authoritarian vs. authoritative), as well as the type of feeding behavior measured. PMID:24976396

Using Flow Characteristics in Three-Dimensional Power Doppler Ultrasound Imaging to Predict Complete Responses in Patients Undergoing Neoadjuvant Chemotherapy.

PubMed

Shia, Wei-Chung; Huang, Yu-Len; Wu, Hwa-Koon; Chen, Dar-Ren

2017-05-01

Strategies are needed for the identification of a poor response to treatment and determination of appropriate chemotherapy strategies for patients in the early stages of neoadjuvant chemotherapy for breast cancer. We hypothesize that power Doppler ultrasound imaging can provide useful information on predicting response to neoadjuvant chemotherapy. The solid directional flow of vessels in breast tumors was used as a marker of pathologic complete responses (pCR) in patients undergoing neoadjuvant chemotherapy. Thirty-one breast cancer patients who received neoadjuvant chemotherapy and had tumors of 2 to 5 cm were recruited. Three-dimensional power Doppler ultrasound with high-definition flow imaging technology was used to acquire the indices of tumor blood flow/volume, and the chemotherapy response prediction was established, followed by support vector machine classification. The accuracy of pCR prediction before the first chemotherapy treatment was 83.87% (area under the ROC curve [AUC] = 0.6957). After the second chemotherapy treatment, the accuracy of was 87.9% (AUC = 0.756). Trend analysis showed that good and poor responders exhibited different trends in vascular flow during chemotherapy. This preliminary study demonstrates the feasibility of using the vascular flow in breast tumors to predict chemotherapeutic efficacy. © 2017 by the American Institute of Ultrasound in Medicine.

Parent feeding behavior and child appetite: associations depend on feeding style.

PubMed

Carnell, Susan; Benson, Leora; Driggin, Elissa; Kolbe, Laura

2014-11-01

Eating behavior traits measured in early life predict eating behavior and weight trajectories later in development, and may be associated with certain parental feeding behaviors. Our goal was to investigate the relationship between a range of feeding behaviors, and preschoolers' appetitive traits. Four hundred thirty-nine parents of UK 3-5 year olds completed scales measuring authoritarian vs. authoritative forms of limiting (Restriction vs. Monitoring) and promoting (Pressuring vs. Prompting) intake, as well as Emotional and Instrumental Feeding. Parents also completed scales measuring child Food responsiveness and Satiety responsiveness. Child BMI z-scores were calculated based on measured heights and weights. Parental Restriction was significantly associated with greater child Food responsiveness (p < .001), but parental Monitoring was not. Parental Pressuring was significantly associated with greater child Satiety responsiveness (p < .001), while parental Prompting was not. Parental Instrumental and Emotional feeding were both associated with greater child Food responsiveness (p < .001). All relationships were independent of child BMI z-score. Prospective data are needed to determine whether the parent-child feeding relationships identified here promote, or protect against, the development of eating pathology in children. However, our results suggest that cross-sectional associations depend on the style (e.g., authoritarian vs. authoritative), as well as the type of feeding behavior measured. © 2014 Wiley Periodicals, Inc.

SU-F-R-48: Early Prediction of Pathological Response of Locally Advanced Rectal Cancer Using Perfusion CT:A Prospective Clinical Study

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

Nie, K; Yue, N; Jabbour, S

Purpose: To prospectively evaluate the tumor vascularity assessed by perfusion CT for prediction of chemo-radiation treatment (CRT) response in locally advanced rectal cancer (LARC). Methods: Eighteen consecutive patients (61.9±8.8 years, from March–June 2015) diagnosed with LARC who underwent 6–8 weeks CRT followed by surgery were included. The pre-treatment perfusion CT was acquired after a 5s delay of contrast agent injection for 45s with 1s interval. A total of 7-cm craniocaudal range covered the tumor region with 3-mm slice thickness. The effective radiation dose is around 15mSv, which is about 1.5 the conventional abdomen/pelvis CT dose. The parametric map of bloodmore » flow (BF), blood volume (BV), mean transit time (MTT), permeability (PMB), and maximum intensity map (MIP) were obtained from commercial software (Syngo-CT 2011A, Siemens). An experienced radiation oncologist outlined the tumor based on the pre-operative MR and pathologic residual region, but was blinded with regards to pathological tumor stage. The perfusion parameters were compared to histopathological response quantified by tumor regression grade as good-responder (GR, TRG 0-1) vs. non-good responder (non-GR). Furthermore, the predictive value for pathological complete response (pCR) was also investigated. Results: Both BV (p=0.02) and MTT (P=0.02) was significantly higher and permeambility was lower (p=0.004) in the good responders. The BF was higher in GR group but not statistically significant. Regarding the discrimination of pCR vs non-pCR, the BF was higher in the pCR group (p=0.08) but none of those parameters showed statistically significant differences. Conclusion: BV and MTT can discriminate patients with a favorable response from those that fail to respond well, potentially selecting high-risk patients with resistant tumors that may benefit from an aggressive preoperative treatment approach. However, future studies with more patient data are needed to verify the prognostic value of perfusion CT especially for pCR prediction. This work is supported by the National High-tech R&D program for Young Scientists by the Ministry of Science and Technology of China (Grant No. 2015AA020917), Natural Science Foundation of China (NSFC Grant No. 81201091).« less

YKL-40/c-Met expression in rectal cancer biopsies predicts tumor regression following neoadjuvant chemoradiotherapy: a multi-institutional study.

PubMed

Senetta, Rebecca; Duregon, Eleonora; Sonetto, Cristina; Spadi, Rossella; Mistrangelo, Massimiliano; Racca, Patrizia; Chiusa, Luigi; Munoz, Fernando H; Ricardi, Umberto; Arezzo, Alberto; Cassenti, Adele; Castellano, Isabella; Papotti, Mauro; Morino, Mario; Risio, Mauro; Cassoni, Paola

2015-01-01

Neoadjuvant chemo-radiotherapy (CRT) followed by surgical resection is the standard treatment for locally advanced rectal cancer, although complete tumor pathological regression is achieved in only up to 30% of cases. A clinicopathological and molecular predictive stratification of patients with advanced rectal cancer is still lacking. Here, c-Met and YKL-40 have been studied as putative predictors of CRT response in rectal cancer, due to their reported involvement in chemoradioresistance in various solid tumors. A multicentric study was designed to assess the role of c-Met and YKL-40 expression in predicting chemoradioresistance and to correlate clinical and pathological features with CRT response. Immunohistochemistry and fluorescent in situ hybridization for c-Met were performed on 81 rectal cancer biopsies from patients with locally advanced rectal adenocarcinoma. All patients underwent standard (50.4 gy in 28 fractions + concurrent capecitabine 825 mg/m2) neoadjuvant CRT or the XELOXART protocol. CRT response was documented on surgical resection specimens and recorded as tumor regression grade (TRG) according to the Mandard criteria. A significant correlation between c-Met and YKL-40 expression was observed (R = 0.43). The expressions of c-Met and YKL-40 were both significantly associated with a lack of complete response (86% and 87% of c-Met and YKL-40 positive cases, p< 0.01 and p = 0.006, respectively). Thirty of the 32 biopsies co-expressing both markers had partial or absent tumor response (TRG 2-5), strengthening their positive predictive value (94%). The exclusive predictive role of YKL-40 and c-Met was confirmed using a multivariate analysis (p = 0.004 and p = 0.007 for YKL-40 and c-Met, respectively). TRG was the sole morphological parameter associated with poor outcome. c-Met and YKL-40 expression is a reliable predictor of partial/absent response to neoadjuvant CRT in rectal cancer. Targeted therapy protocols could take advantage of prior evaluations of c-MET and YKL-40 expression levels to increase therapeutic efficacy.

Preoperative chemoradiotherapy with capecitabine versus protracted infusion 5-fluorouracil for rectal cancer: A matched-pair analysis

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

Das, Prajnan; Lin, Edward H.; Bhatia, Sumita

2006-12-01

Purpose: To retrospectively compare the acute toxicity, pathologic response, relapse rates, and survival in rectal cancer patients treated with preoperative radiotherapy (RT) and either concurrent capecitabine or concurrent protracted infusion 5-fluorouracil (5-FU). Methods: Between June 2001 and February 2004, 89 patients with nonmetastatic rectal adenocarcinoma were treated with preoperative RT and concurrent capecitabine, followed by mesorectal excision. These patients were individually matched by clinical T and N stage (as determined by endoscopic ultrasound and CT scans) with 89 control patients treated with preoperative RT and concurrent protracted infusion 5-FU between September 1997 and August 2002. Results: In each group, 5more » patients (6%) had Grade 3-4 toxicity during chemoradiotherapy. The pathologic complete response rate was 21% with capecitabine and 12% with protracted infusion 5-FU (p = 0.19). Of the 89 patients in the capecitabine group and 89 in the 5-FU group, 46 (52%) and 55 (62%), respectively, had downstaging of the T stage after chemoradiotherapy (p = 0.20). The estimated 3-year local control (p = 0.15), distant control (p = 0.86), and overall survival (p = 0.12) rate was 94.4%, 86.3%, and 89.8% for patients treated with capecitabine and 98.6%, 86.6%, and 96.4% for patients treated with protracted infusion 5-FU, respectively. Conclusion: Preoperative concurrent capecitabine and concurrent protracted infusion 5-FU were both well tolerated, with similar, low rates of Grade 3-4 acute toxicity. No significant differences were seen in the pathologic response, local and distant recurrence, or overall survival among patients treated with preoperative RT and concurrent capecitabine compared with those treated with RT and concurrent protracted infusion 5-FU.« less

Preoperative Capecitabine and Pelvic Radiation in Locally Advanced Rectal Cancer-Is it Equivalent to 5-FU Infusion Plus Leucovorin and Radiotherapy?

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

Chan, Alexander K., E-mail: alexc@cancerboard.ab.c; Wong, Alfred O.; Jenken, Daryl A.

2010-04-15

Purpose: The aim of this retrospective case-matching study was to compare the treatment outcomes and acute toxicity of preoperative radiotherapy (RT) with capecitabine vs. preoperative RT with intermittent 5-fluorouracil (5-FU) infusion, leucovorin, and mitomycin C in rectal cancer. Methods and Materials: We matched 34 patients who were treated with preoperative concurrent capecitabine and 50 Gy of RT by their clinical T stage (T3 or T4) and the tumor location (<=7 cm or >7 cm from the anal verge) with another 68 patients who were treated with preoperative intermittent 5-FU infusion, leucovorin, mitomycin C, and 50 Gy of RT for amore » comparison of the pathologic tumor response, local control, distant failure, and survival rates. Results: The pathologic complete response rate was 21% with capecitabine and 18% with 5-FU and leucovorin (p = 0.72). The rate of T downstaging after chemoradiation was 59% for both groups. The rate of sphincter-sparing resection was 38% after capecitabine plus RT and 43% after 5-FU plus RT (p = 0.67). At 3 years, there was no significant difference in the local control rate (93% for capecitabine and 92% for 5-FU and leucovorin), relapse-free rate (74% for capecitabine and 73% for 5-FU and leucovorin), or disease-specific survival rate (86% for capecitabine and 77% for 5-FU and leucovorin). The acute toxicity profile was comparable, with little Grade 3 and 4 toxicity. Conclusions: When administered with concurrent preoperative RT, both capecitabine and intermittent 5-FU infusion with leucovorin modulation provided comparable pathologic tumor response, local control, relapse-free survival, and disease-specific survival rates in rectal cancer.« less

The Differential Contribution of the Innate Immune System to a Good Pathological Response in the Breast and Axillary Lymph Nodes Induced by Neoadjuvant Chemotherapy in Women with Large and Locally Advanced Breast Cancers

PubMed Central

Verma, Chandan; Eremin, Jennifer M.; Cowley, Gerard; Ilyas, Mohammad; Satthaporn, Sukchai; Eremin, Oleg

2017-01-01

The tumour microenvironment consists of malignant cells, stroma, and immune cells. The role of adaptive immunity in inducing a pathological complete response (pCR) in breast cancer with neoadjuvant chemotherapy (NAC) is well studied. The contribution of innate immunity, however, is poorly documented. Breast tumours and axillary lymph nodes (ALNs) from 33 women with large and locally advanced breast cancers (LLABCs) undergoing NAC were immunohistochemically assessed for tumour-infiltrating macrophages (TIMs: M1 and M2), neutrophils (TINs), and dendritic cells (TIDCs) using labelled antibodies and semiquantitative methods. Patients' blood neutrophils (n = 108), DCs (mDC1 and pDC), and their costimulatory molecules (n = 30) were also studied. Pathological results were classified as pCR, good (GPR) or poor (PRR). In breast and metastatic ALNs, high levels of CD163+ TIMs were significantly associated with a pCR. In blood, high levels of neutrophils were significantly associated with pCR in metastatic ALNs, whilst the % of mDC1 and pDC and expression of HLA-DR, mDC1 CD40, and CD83 were significantly reduced. NAC significantly reduced tumour DCs but increased blood DCs. PPRs to NAC had significantly reduced HLA-DR, CD40, and CD86 expression. Our study demonstrated novel findings documenting the differential but important contributions of innate immunity to pCRs in patients with LLABCs undergoing NAC. PMID:28913366

Prediction of Chemoresistance in Women Undergoing Neo-Adjuvant Chemotherapy for Locally Advanced Breast Cancer: Volumetric Analysis of First-Order Textural Features Extracted from Multiparametric MRI

PubMed Central

Losio, C.; Della Corte, A.; Venturini, E.; Ambrosi, A.; Panizza, P.; De Cobelli, F.

2018-01-01

Purpose To assess correlations between volumetric first-order texture parameters on baseline MRI and pathological response after neoadjuvant chemotherapy (NAC) for locally advanced breast cancer (BC). Materials and Methods 69 patients with locally advanced BC candidate to neoadjuvant chemotherapy underwent MRI within 4 weeks from the start of therapeutic regimen. T2, DWI, and DCE sequences were analyzed and maps were generated for Apparent Diffusion Coefficient (ADC), T2 signal intensity, and the following dynamic parameters: k-trans, peak enhancement, area under curve (AUC), time to maximal enhancement (TME), wash-in rate, and washout rate. Volumetric analysis of these parameters was performed, yielding a histogram analysis including first-order texture kinetics (percentiles, maximum value, minimum value, range, standard deviation, mean, median, mode, skewness, and kurtosis). Finally, correlations between these values and response to NAC (evaluated on the surgical specimen according to RECIST 1.1 criteria) were assessed. Results Out of 69 tumors, 33 (47.8%) achieved complete pathological response, 26 (37.7%) partial response, and 10 (14.5%) no response. Higher levels of AUCmax (p value = 0.0338), AUCrange (p value = 0.0311), and TME75 (p value = 0.0452) and lower levels of washout10 (p value = 0.0417), washout20 (p value = 0.0138), washout25 (p value = 0.0114), and washout30 (p value = 0.05) were predictive of noncomplete response. Conclusion Histogram-derived texture analysis of MRI images allows finding quantitative parameters predictive of nonresponse to NAC in women affected by locally advanced BC. PMID:29853811

Prediction of Chemoresistance in Women Undergoing Neo-Adjuvant Chemotherapy for Locally Advanced Breast Cancer: Volumetric Analysis of First-Order Textural Features Extracted from Multiparametric MRI.

PubMed

Panzeri, M M; Losio, C; Della Corte, A; Venturini, E; Ambrosi, A; Panizza, P; De Cobelli, F

2018-01-01

To assess correlations between volumetric first-order texture parameters on baseline MRI and pathological response after neoadjuvant chemotherapy (NAC) for locally advanced breast cancer (BC). 69 patients with locally advanced BC candidate to neoadjuvant chemotherapy underwent MRI within 4 weeks from the start of therapeutic regimen. T2, DWI, and DCE sequences were analyzed and maps were generated for Apparent Diffusion Coefficient (ADC), T2 signal intensity, and the following dynamic parameters: k -trans, peak enhancement, area under curve (AUC), time to maximal enhancement (TME), wash-in rate, and washout rate. Volumetric analysis of these parameters was performed, yielding a histogram analysis including first-order texture kinetics (percentiles, maximum value, minimum value, range, standard deviation, mean, median, mode, skewness, and kurtosis). Finally, correlations between these values and response to NAC (evaluated on the surgical specimen according to RECIST 1.1 criteria) were assessed. Out of 69 tumors, 33 (47.8%) achieved complete pathological response, 26 (37.7%) partial response, and 10 (14.5%) no response. Higher levels of AUCmax ( p value = 0.0338), AUCrange ( p value = 0.0311), and TME 75 ( p value = 0.0452) and lower levels of washout 10 ( p value = 0.0417), washout 20 ( p value = 0.0138), washout 25 ( p value = 0.0114), and washout 30 ( p value = 0.05) were predictive of noncomplete response. Histogram-derived texture analysis of MRI images allows finding quantitative parameters predictive of nonresponse to NAC in women affected by locally advanced BC.

Long-Term Prognostic Risk After Neoadjuvant Chemotherapy Associated With Residual Cancer Burden and Breast Cancer Subtype

PubMed Central

Wei, Caimiao; Gould, Rebekah; Yu, Xian; Zhang, Ya; Liu, Mei; Walls, Andrew; Bousamra, Alex; Ramineni, Maheshwari; Sinn, Bruno; Hunt, Kelly; Buchholz, Thomas A.; Valero, Vicente; Buzdar, Aman U.; Yang, Wei; Brewster, Abenaa M.; Moulder, Stacy; Pusztai, Lajos; Hatzis, Christos; Hortobagyi, Gabriel N.

2017-01-01

Purpose To determine the long-term prognosis in each phenotypic subset of breast cancer related to residual cancer burden (RCB) after neoadjuvant chemotherapy alone, or with concurrent human epidermal growth factor receptor 2 (HER2)–targeted treatment. Methods We conducted a pathologic review to measure the continuous RCB index (wherein pathologic complete response has RCB = 0; residual disease is categorized into three predefined classes of RCB index [RCB-I, RCB-II, and RCB-III]), and yp-stage of residual disease. Patients were prospectively observed for survival. Three patient cohorts received paclitaxel (T) followed by fluorouracil, doxorubicin, and cyclophosphamide (T/FAC): original development cohort (T/FAC-1), validation cohort (T/FAC-2), and independent validation cohort (T/FAC-3). Another validation cohort received FAC chemotherapy only, and a fifth cohort received concurrent trastuzumab (H) with sequential paclitaxel and fluorouracil, epirubicin, and cyclophosphamide (FEC; H+T/FEC). Phenotypic subsets were defined by hormone receptor (HR) and HER2 status at diagnosis, classified as HR-positive/HER2-negative, HER2-positive (HR-negative/HER2-positive or HR-positive/HER2-positive), or triple receptor–negative. Relapse-free survival estimates were determined from Kaplan-Meier analysis and compared using the log-rank test. Results Five cohorts (T/FAC-1 [n = 219], T/FAC-2 [n = 262], T/FAC-3 [n = 342], FAC [n = 132], and H+T/FEC [n = 203]) had median event-free follow-up of 13.5, 9.1, 6.8, 16.4, and 7.1 years, respectively. Continuous RCB index was prognostic within each phenotypic subset, independent of other clinical-pathologic variables. RCB classes stratified prognostic risk overall, within each phenotypic subset, and within yp-stage categories. Estimates of 10-year relapse-free survival rates in the four RCB classes (pathologic complete response, RCB-I, RCB-II, and RCB-III) were 86%, 81%, 55%, and 23% for triple receptor–negative; 83%, 97%, 74%, and 52% for HR-positive/HER2-negative in the combined T/FAC cohorts; and 95%, 77%, 47%, and 21% in the H+T/FEC cohort. Conclusion RCB was prognostic for long-term survival after neoadjuvant chemotherapy in all three phenotypic subsets of breast cancer. Our institutional findings should be externally validated. PMID:28135148

Physician satisfaction with surgical pathology reports: a 2-year College of American Pathologists Q-Tracks Study.

PubMed

Nakhleh, Raouf E; Souers, Rhona; Ruby, Stephen G

2008-11-01

There are multiple elements that can be measured to assess the quality of a surgical pathology laboratory. Overall customer satisfaction is an excellent "global" measure, because it highlights the unique insight of laboratory performance from the users' perspective. To measure customer satisfaction with surgical pathology reports. This study was based on a subscription Q-Tracks study. Voluntary participants were asked to distribute and collect a minimum of 25 surveys per quarter from their clients. Four parameters were graded, which included overall satisfaction, report turnaround time (TAT), completeness, and style on a scale of 1 (poor) to 5 (excellent). Each laboratory submitted quarterly data to the College of American Pathologists, where the data were tabulated and analyzed. Each laboratory could compare their performance in all 4 measures against the entire cohort or a selected subgroup of laboratories. Overall customer satisfaction with surgical pathology reports and 3 subcategories of report TAT, completeness, and style were the main outcome measures. This study ran during 2004 and 2005, with 41 and 33 participant laboratories, respectively. The median score for overall satisfaction, TAT, completeness, and style were 4.57, 4.31, 4.62, and 4.64 in 2004, and 4.64, 4.56, 4.65, and 4.68 in 2005, respectively. Most laboratories reported results for 4 quarters or fewer. There was no statistically significant change in overall satisfaction over time. Overall satisfaction scores for surgical pathology reports as well as satisfaction with report TAT, completeness, and style were high. Report TAT received the lowest scores of all parameters.

Future directions in training veterinarians for careers in toxicological pathology in the United Kingdom.

PubMed

Scudamore, Cheryl L; Smith, Sionagh H

2007-01-01

There is currently a global shortage of veterinary pathologists in all sectors of the discipline, and recruitment of toxicological pathologists is a particular problem for the pharmaceutical industry. Efforts to encourage veterinarians to consider alternative career paths to general practice must start at the undergraduate level, with provision of structured career guidance and strong role models from pathology and research disciplines. It is also imperative that both the importance of biomedical research and the role of animal models be clearly understood by both university staff and undergraduates. Traditionally, much post-graduate training in toxicological pathology is done "on the job" in the United Kingdom, but completion of a residency and/or PhD program is recognized as a good foundation for a career in industry and for successful completion of professional pathology examinations. New models of residency training in veterinary pathology must be considered in the United Kingdom to enable a more tailored approach to training toward specific career goals. A modular approach to residency training would allow core skills to be maintained, while additional training would target specific training requirements in toxicological pathology. Exposure to laboratory-animal pathology, toxicology, research methodology, and management skills would all be of benefit as an introduction to a career in toxicological pathology. However, long-term funding for UK residencies remains a problem that must be resolved if future recruitment needs in veterinary pathology are to be met.

Interpersonal guilt in college student pathological gamblers

PubMed Central

Locke, Geoffrey W.; Shilkret, Robert; Everett, Joyce E.; Petry, Nancy M.

2013-01-01

Background Interpersonal guilt is associated with psychopathology, but its relationship to pathological gambling has not been studied. Objectives This study examined the relationship between interpersonal guilt and pathological gambling. Methods In total, 1,979 college students completed a questionnaire containing the South Oaks Gambling Screen, Interpersonal Guilt Questionnaire, and questions about substance use. Students identified as pathological gamblers (n = 145) were matched to non-problem gamblers with respect to demographics and substance use. Results Pathological gamblers had significantly higher interpersonal guilt than their non-problem gambling peers. Conclusions and Scientific Significance Pathological gambling college students have excessive interpersonal guilt, and these findings may lead to novel treatment approaches. PMID:22746179

[Systemic immunological response in children with chronic gingivitis and gastro-intestinal pathology].

PubMed

Romanenko, E G

2014-01-01

Study of the immune system mechanisms in chronic catarrhal gingivitis in children with gastrointestinal pathology was performed in 102 children (49 with chronic gastritis and duodenitis and 53 with no signs of gastrointestinal pathology). Forty-eight children with healthy periodontium constituted control group. Generalized chronic catarrhal gingivitis in children with gastroduodenal pathology is characterized by intense humoral response by simultaneous T-cell immunity suppression. Detection of high serum titers of circulating immune complexes in patients with chronic catarrhal gingivitis suggests a role of immune response in the pathogenesis of periodontal disease increases with concomitant diseases of the upper gastrointestinal tract.

Sequential cisplatin/cyclophosphamide chemotherapy and abdominopelvic radiotherapy in the management of advanced ovarian cancer.

PubMed Central

Green, J. A.; Warenius, H. M.; Errington, R. D.; Myint, S.; Spearing, G.; Slater, A. J.

1988-01-01

Forty-six previously untreated patients with advanced ovarian cancer were treated with combination chemotherapy comprising cisplatin 80 mg m-2 i.v. and cyclophosphamide 1 gm-2 i.v. every 28 days for 5 cycles. Eighty-five percent of patients received more than 75% of the calculated doses, and of 43 evaluable patients, a complete response was achieved in 31 (72%), a partial response in 4 (9.3%) and 8 patients had static or progressive disease. The actuarial survival of the whole group is 60% at a median follow-up of 2 years. Twenty-four patients in complete clinical or pathological remission were then treated with whole abdominal radiotherapy 2,500 cGy followed by a pelvic boost of 2,000 cGy. The pelvic boost was omitted in 3 patients, and the overall radiotherapy treatment time extended in a further 4 patients on account of myelosuppression. The actuarial survival of the 24 patients receiving both treatments at a median of 30 months follow-up is 75%. In the 10 patients with negative second-look procedures completing both treatments there have been no tumour related deaths at a median follow-up of 33 months. PMID:3219276

Sequential cisplatin/cyclophosphamide chemotherapy and abdominopelvic radiotherapy in the management of advanced ovarian cancer.

PubMed

Green, J A; Warenius, H M; Errington, R D; Myint, S; Spearing, G; Slater, A J

1988-11-01

Forty-six previously untreated patients with advanced ovarian cancer were treated with combination chemotherapy comprising cisplatin 80 mg m-2 i.v. and cyclophosphamide 1 gm-2 i.v. every 28 days for 5 cycles. Eighty-five percent of patients received more than 75% of the calculated doses, and of 43 evaluable patients, a complete response was achieved in 31 (72%), a partial response in 4 (9.3%) and 8 patients had static or progressive disease. The actuarial survival of the whole group is 60% at a median follow-up of 2 years. Twenty-four patients in complete clinical or pathological remission were then treated with whole abdominal radiotherapy 2,500 cGy followed by a pelvic boost of 2,000 cGy. The pelvic boost was omitted in 3 patients, and the overall radiotherapy treatment time extended in a further 4 patients on account of myelosuppression. The actuarial survival of the 24 patients receiving both treatments at a median of 30 months follow-up is 75%. In the 10 patients with negative second-look procedures completing both treatments there have been no tumour related deaths at a median follow-up of 33 months.

Altering Response Chains in Pathological Gamblers Using a Response-Cost Procedure

ERIC Educational Resources Information Center

Johnson, Taylor E.; Dixon, Mark R.

2009-01-01

Two pathological gamblers could choose between emitting or having the dealer emit the response options when playing each of three casino games. A response-cost procedure was introduced in a multiple baseline design across games in which the participant had to pay to perform the responses himself, which was somewhat effective at reducing many of…

Relationship between maternal immunological response during pregnancy and onset of preeclampsia.

PubMed

Martínez-Varea, Alicia; Pellicer, Begoña; Perales-Marín, Alfredo; Pellicer, Antonio

2014-01-01

Maternofetal immune tolerance is essential to maintain pregnancy. The maternal immunological tolerance to the semiallogeneic fetus becomes greater in egg donation pregnancies with unrelated donors as the complete fetal genome is allogeneic to the mother. Instead of being rejected, the allogeneic fetus is tolerated by the pregnant woman in egg donation pregnancies. It has been reported that maternal morbidity during egg donation pregnancies is higher as compared with spontaneous or in vitro fertilization pregnancies. Particularly, egg donation pregnancies are associated with a higher incidence of pregnancy-induced hypertension and placental pathology. Preeclampsia, a pregnancy-specific disease characterized by the development of both hypertension and proteinuria, remains the leading cause of maternal and perinatal mortality and morbidity. The aim of this review is to characterize and relate the maternofetal immunological tolerance phenomenon during pregnancies with a semiallogenic fetus, which are the spontaneously conceived pregnancies and in vitro fertilization pregnancies, and those with an allogeneic fetus or egg donation pregnancies. Maternofetal immune tolerance in uncomplicated pregnancies and pathological pregnancies, such as those with preeclampsia, has also been assessed. Moreover, whether an inadequate maternal immunological response to the allogenic fetus could lead to a higher prevalence of preeclampsia in egg donation pregnancies has been addressed.

Knowledge of memory aging across the lifespan.

PubMed

Cherry, Katie E; Blanchard, Blakeley; Walker, Erin J; Smitherman, Emily A; Lyon, Bethany A

2014-01-01

The authors examined knowledge of normal and pathological memory aging in a lifespan sample of 198 individuals who ranged in age from 13 to 88 years. Participants completed the Knowledge of Memory Aging Questionnaire (Cherry, Brigman, Hawley, & Reese, 2003). The authors hypothesized that high school students would be less knowledgeable about memory aging issues than college students, middle-aged, and community-dwelling older adults. Consistent with this hypothesis, response accuracy was lower for high school students compared to their older counterparts. Follow-up analyses revealed that high school students' responses to a subset of questions that tap ageist views of adult cognition were less accurate than the other age groups, implying a response bias toward stereotypical images of memory aging. Implications for research and the design of instructional materials to increase people's knowledge about normative changes in adult cognition are discussed.

Meta-analysis on the association between pathologic complete response and triple-negative breast cancer after neoadjuvant chemotherapy.

PubMed

Wu, Kunpeng; Yang, Qiaozhu; Liu, Yi; Wu, Aibing; Yang, Zhixiong

2014-04-15

Triple-negative breast cancer (TNBC) is a special subtype of breast cancer that is characterized by poor prognosis, strong tumor invasion and a high pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC). The pCR rate is a prognostic factor for TNBC. We aimed to evaluate the relationship between pCR and TNBC after NAC and originally tried to identify factors related to achieving pCR for TNBC using a meta-analysis. We systematically searched the literature for pCR and breast cancer after NAC and carefully identified eligibility criteria. The association between pCR and breast cancer subtypes was estimated using Review Manager, while pCR rates for TNBC and non-TNBC were determined using Meta-Analyst. This analysis included a total of 9,460 cases from 27 studies. The summary odds ratio estimating the relationship between pCR and breast cancer subtypes (TNBC vs non-TNBC) was 3.02 (95% confidence interval (CI), 2.66 to 3.42). The TNBC pCR rate was 28.9% (95% CI, 27.0 to 30.8%) and the non-TNBC was 12.5% (95% CI, 11.7 to 13.4%). From subgroup analyses, we identified the factors associated with the highest pCR rates for TNBC. TNBC has a higher pCR rate than non-TNBC. In the NAC setting, these factors of platinum-containing, more than six cycles, four kinds of drugs, 16 weeks' treatment duration and sequential chemotherapy may contribute to increasing the pCR rate.

Expression of p53 protein in advanced head and neck squamous cell carcinoma before and after chemotherapy.

PubMed

Dunphy, C H; Dunphy, F R; Boyd, J H; Varvares, M A; Kim, H J; Lowe, V; Dunleavy, T L; Rodriguez, J; McDonough, E M; Minster, J

1997-11-01

The expression of p53 protein has been reported to be in the range of 35% to 67% in head and neck squamous cell carcinoma (HNSCC). Mutations of the gene for p53 protein have been associated with rapidly proliferating tumors, and p53 protein expression has been shown to be a significant predictor of worse survival in surgically resected HNSCC. To determine whether p53 protein expression in advanced (stages III and IV) HNSCC has any impact on tumor response to 2 to 3 courses of paclitaxel (Taxol) and carboplatin, we prospectively studied prechemotherapy specimens from patients with previously untreated, advanced-stage HNSCC. We also attempted to study residual tumors after chemotherapy to determine if the p53 status of the tumor changed. The expression of p53 protein was evaluated by immunohistochemical analysis (clone BP53-12-1; Bio-Genex, San Ramon, Calif). Tertiary university medical center. Two to 3 courses of chemotherapy with paclitaxel and carboplatin. Pathologic complete remission or residual tumor. The results of p53 immunostaining were positive in 24 (67%) of 36 HNSCC specimens before chemotherapy. After chemotherapy, 8 patients achieved pathologic complete remission. Before chemotherapy, the tumor was p53 negative in 2 patients and positive in 6 patients. No correlation of p53 protein expression with response to chemotherapy was noted. The expression of p53 protein converted from positive to negative in 5 (42%) of 12 specimens from patients with residual tumor after chemotherapy, with no impact on clinical outcome.

Circulating myeloid-derived suppressor cells increase in patients undergoing neo-adjuvant chemotherapy for breast cancer.

PubMed

Wesolowski, Robert; Duggan, Megan C; Stiff, Andrew; Markowitz, Joseph; Trikha, Prashant; Levine, Kala M; Schoenfield, Lynn; Abdel-Rasoul, Mahmoud; Layman, Rachel; Ramaswamy, Bhuvaneswari; Macrae, Erin R; Lustberg, Maryam B; Reinbolt, Raquel E; Mrozek, Ewa; Byrd, John C; Caligiuri, Michael A; Mace, Thomas A; Carson, William E

2017-11-01

This study sought to evaluate whether myeloid-derived suppressor cells (MDSC) could be affected by chemotherapy and correlate with pathologic complete response (pCR) in breast cancer patients receiving neo-adjuvant chemotherapy. Peripheral blood levels of granulocytic (G-MDSC) and monocytic (M-MDSC) MDSC were measured by flow cytometry prior to cycle 1 and 2 of doxorubicin and cyclophosphamide and 1st and last administration of paclitaxel or paclitaxel/anti-HER2 therapy. Of 24 patients, 11, 6 and 7 patients were triple negative, HER2+ and hormone receptor+, respectively. 45.8% had pCR. Mean M-MDSC% were <1. Mean G-MDSC% and 95% confidence intervals were 0.88 (0.23-1.54), 5.07 (2.45-7.69), 9.32 (4.02-14.61) and 1.97 (0.53-3.41) at draws 1-4. The increase in G-MDSC by draw 3 was significant (p < 0.0001) in all breast cancer types. G-MDSC levels at the last draw were numerically lower in patients with pCR (1.15; 95% CI 0.14-2.16) versus patients with no pCR (2.71; 95% CI 0-5.47). There was no significant rise in G-MDSC from draw 1 to 3 in African American patients, and at draw 3 G-MDSC levels were significantly lower in African Americans versus Caucasians (p < 0.05). It was concluded that G-MDSC% increased during doxorubicin and cyclophosphamide therapy, but did not significantly differ between patients based on pathologic complete response.

Preoperative Short-Course Concurrent Chemoradiation Therapy Followed by Delayed Surgery for Locally Advanced Rectal Cancer: A Phase 2 Multicenter Study (KROG 10-01)

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

Yeo, Seung-Gu; Department of Radiation Oncology, Soonchunhyang University College of Medicine, Cheonan; Oh, Jae Hwan

Purpose: A prospective phase 2 multicenter trial was performed to investigate the efficacy and safety of preoperative short-course concurrent chemoradiation therapy (CRT) followed by delayed surgery for patients with locally advanced rectal cancer. Methods and Materials: Seventy-three patients with cT3-4 rectal cancer were enrolled. Radiation therapy of 25 Gy in 5 fractions was delivered over 5 consecutive days using helical tomotherapy. Concurrent chemotherapy was administered on the same 5 days with intravenous bolus injection of 5-fluorouracil (400 mg/m{sup 2}/day) and leucovorin (20 mg/m{sup 2}/day). After 4 to 8 weeks, total mesorectal excision was performed. The primary endpoint was the pathologicmore » downstaging (ypStage 0-I) rate, and secondary endpoints included tumor regression grade, tumor volume reduction rate, and toxicity. Results: Seventy-one patients completed the planned preoperative CRT and surgery. Downstaging occurred in 20 (28.2%) patients, including 1 (1.4%) with a pathologic complete response. Favorable tumor regression (grade 4-3) was observed in 4 (5.6%) patients, and the mean tumor volume reduction rate was 62.5 ± 21.3%. Severe (grade ≥3) treatment toxicities were reported in 27 (38%) patients from CRT until 3 months after surgery. Conclusions: Preoperative short-course concurrent CRT followed by delayed surgery for patients with locally advanced rectal cancer demonstrated poor pathologic responses compared with conventional long-course CRT, and it yielded considerable toxicities despite the use of an advanced radiation therapy technique.« less

Flexible intramedullary nailing for the treatment of unicameral bone cysts in long bones.

PubMed

Roposch, A; Saraph, V; Linhart, W E

2000-10-01

Unicameral bone cyst is characterized by its tenacity and risk of recurrence. Pathological fracture is common and is often the presenting symptom. The objective of the present study was to evaluate the results of flexible intramedullary nailing for the treatment of a unicameral bone cyst with or without a pathological fracture. Flexible intramedullary nailing for the treatment of a unicameral bone cyst was performed in thirty-two patients. Thirty of these patients presented with a pathological fracture; twenty-four were managed immediately with intramedullary nailing, and the other six had been managed conservatively at other clinics before they were referred to our department. The remaining two cysts were detected incidentally. The cyst was located in the humerus in twenty-one patients, in the femur in nine, and in the radius in two. The mean age of the patients at the time of surgery was 9.8 years, and the mean duration of follow-up was 53.7 months. Radiographic evaluation was performed according to the criteria of Capanna et al., and the cyst was classified as completely healed, healed with residual radiolucency (osteolysis), recurred, or having no response. The healing period ranged from three to 105 months. Fourteen cysts healed completely, and sixteen healed with residual radiolucent areas visible on radiographs. There was recurrence of two cysts that had healed with residual radiolucency. All of the cysts in the present study responded to treatment. A change of nails was necessary in nine patients, as the nails had become too short after bone growth. No major complications were observed. Flexible intramedullary nailing provides early stability, which allows early mobilization and thus obviates the need for a plaster cast and decreases the prevalence of the most common complication: a pathological fracture. This method of treatment also allows for an early return to normal activity.

CD8+IL-17+ T Cells Mediate Neutrophilic Airway Obliteration in T-bet–Deficient Mouse Lung Allograft Recipients

PubMed Central

Dodd-o, Jeffrey M.; Coon, Tiffany A.; Miller, Hannah L.; Ganguly, Sudipto; Popescu, Iulia; O'Donnell, Christopher P.; Cardenes, Nayra; Levine, Melanie; Rojas, Mauricio; Weathington, Nathaniel M.; Zhao, Jing; Zhao, Yutong; McDyer, John F.

2015-01-01

Acute cellular rejection is a known risk factor for the development of obliterative bronchiolitis, which limits the long-term survival of lung transplant recipients. However, the T cell effector mechanisms in both of these processes remain incompletely understood. Using the mouse orthotopic lung transplant model, we investigated whether C57BL/6 T-bet−/− recipients of major histocompatibility complex (MHC)-mismatched BALB/c lung grafts develop rejection pathology and allospecific cytokine responses that differ from wild-type mice. T-bet−/− recipients demonstrated vigorous allograft rejection at 10 days, characterized by neutrophilic inflammation and predominantly CD8+ T cells producing allospecific IL-17 and/or IFN-γ, in contrast to IFN-γ–dominant responses in WT mice. CD4+ T cells produced IL-17 but not IFN-γ responses in T-bet−/− recipients, in contrast to WT controls. Costimulation blockade using anti-CD154 Ab significantly reduced allospecific CD8+IFN-γ+ responses in both T-bet−/− and WT mice but had no attenuating effect on lung rejection pathology in T-bet−/− recipients or on the development of obliterative airway inflammation that occurred only in T-bet−/− recipients. However, neutralization of IL-17A significantly attenuated costimulation blockade–resistant rejection pathology and airway inflammation in T-bet−/− recipients. In addition, CXCL1 (neutrophil chemokine) was increased in T-bet−/− allografts, and IL-17 induced CXCL1 from mouse lung epithelial cells in vitro. Taken together, our data show that T-bet–deficient recipients of complete MHC-mismatched lung allografts develop costimulation blockade–resistant rejection characterized by neutrophilia and obliterative airway inflammation that is predominantly mediated by CD8+IL-17+ T cells. Our data support T-bet–deficient mouse recipients of lung allografts as a viable animal model to study the immunopathogenesis of small airway injury in lung transplantation. PMID:25286244

Imbalanced pattern completion vs. separation in cognitive disease: network simulations of synaptic pathologies predict a personalized therapeutics strategy.

PubMed

Hanson, Jesse E; Madison, Daniel V

2010-08-13

Diverse Mouse genetic models of neurodevelopmental, neuropsychiatric, and neurodegenerative causes of impaired cognition exhibit at least four convergent points of synaptic malfunction: 1) Strength of long-term potentiation (LTP), 2) Strength of long-term depression (LTD), 3) Relative inhibition levels (Inhibition), and 4) Excitatory connectivity levels (Connectivity). To test the hypothesis that pathological increases or decreases in these synaptic properties could underlie imbalances at the level of basic neural network function, we explored each type of malfunction in a simulation of autoassociative memory. These network simulations revealed that one impact of impairments or excesses in each of these synaptic properties is to shift the trade-off between pattern separation and pattern completion performance during memory storage and recall. Each type of synaptic pathology either pushed the network balance towards intolerable error in pattern separation or intolerable error in pattern completion. Imbalances caused by pathological impairments or excesses in LTP, LTD, inhibition, or connectivity, could all be exacerbated, or rescued, by the simultaneous modulation of any of the other three synaptic properties. Because appropriate modulation of any of the synaptic properties could help re-balance network function, regardless of the origins of the imbalance, we propose a new strategy of personalized cognitive therapeutics guided by assay of pattern completion vs. pattern separation function. Simulated examples and testable predictions of this theorized approach to cognitive therapeutics are presented.

Refining pathological evaluation of neoadjuvant therapy for adenocarcinoma of the esophagus

PubMed Central

Noble, Fergus; Nolan, Luke; Bateman, Adrian C; Byrne, James P; Kelly, Jamie J; Bailey, Ian S; Sharland, Donna M; Rees, Charlotte N; Iveson, Timothy J; Underwood, Tim J; Bateman, Andrew R

2013-01-01

AIM: To assess tumour regression grade (TRG) and lymph node downstaging to help define patients who benefit from neoadjuvant chemotherapy. METHODS: Two hundred and eighteen consecutive patients with adenocarcinoma of the esophagus or gastro-esophageal junction treated with surgery alone or neoadjuvant chemotherapy and surgery between 2005 and 2011 at a single institution were reviewed. Triplet neoadjuvant chemotherapy consisting of platinum, fluoropyrimidine and anthracycline was considered for operable patients (World Health Organization performance status ≤ 2) with clinical stage T2-4 N0-1. Response to neoadjuvant chemotherapy (NAC) was assessed using TRG, as described by Mandard et al. In addition lymph node downstaging was also assessed. Lymph node downstaging was defined by cN1 at diagnosis: assessed radiologically (computed tomography, positron emission tomography, endoscopic ultrasonography), then pathologically recorded as N0 after surgery; ypN0 if NAC given prior to surgery, or pN0 if surgery alone. Patients were followed up for 5 years post surgery. Recurrence was defined radiologically, with or without pathological confirmation. An association was examined between t TRG and lymph node downstaging with disease free survival (DFS) and a comprehensive range of clinicopathological characteristics. RESULTS: Two hundred and eighteen patients underwent esophageal resection during the study interval with a mean follow up of 3 years (median follow up: 2.552, 95%CI: 2.022-3.081). There was a 1.8% (n = 4) inpatient mortality rate. One hundred and thirty-six (62.4%) patients received NAC, with 74.3% (n = 101) of patients demonstrating some signs of pathological tumour regression (TRG 1-4) and 5.9% (n = 8) having a complete pathological response. Forty four point one percent (n = 60) had downstaging of their nodal disease (cN1 to ypN0), compared to only 15.9% (n = 13) that underwent surgery alone (pre-operatively overstaged: cN1 to pN0), (P < 0.0001). Response to NAC was associated with significantly increased DFS (mean DFS; TRG 1-2: 5.1 years, 95%CI: 4.6-5.6 vs TRG 3-5: 2.8 years, 95%CI: 2.2-3.3, P < 0.0001). Nodal down-staging conferred a significant DFS advantage for those patients with a poor primary tumour response to NAC (median DFS; TRG 3-5 and nodal down-staging: 5.533 years, 95%CI: 3.558-7.531 vs TRG 3-5 and no nodal down-staging: 1.114 years, 95%CI: 0.961-1.267, P < 0.0001). CONCLUSION: Response to NAC in the primary tumour and in the lymph nodes are both independently associated with improved DFS. PMID:24409055

Five years of experience teaching pathology to dental students using the WebMicroscope

PubMed Central

2011-01-01

Background We describe development and evaluation of the user-friendly web based virtual microscopy - WebMicroscope for teaching and learning dental students basic and oral pathology. Traditional students microscopes were replaced by computer workstations. Methods The transition of the basic and oral pathology courses from light to virtual microscopy has been completed gradually over a five-year period. A pilot study was conducted in academic year 2005/2006 to estimate the feasibility of integrating virtual microscopy into a traditional light microscopy-based pathology course. The entire training set of glass slides was subsequently converted to virtual slides and placed on the WebMicroscope server. Giving access to fully digitized slides on the web with a browser and a viewer plug-in, the computer has become a perfect companion of the student. Results The study material consists now of over 400 fully digitized slides which covering 15 entities in basic and systemic pathology and 15 entities in oral pathology. Digitized slides are linked with still macro- and microscopic images, organized with clinical information into virtual cases and supplemented with text files, syllabus, PowerPoint presentations and animations on the web, serving additionally as material for individual studies. After their examinations, the students rated the use of the software, quality of the images, the ease of handling the images, and the effective use of virtual slides during the laboratory practicals. Responses were evaluated on a standardized scale. Because of the positive opinions and support from the students, the satisfaction surveys had shown a progressive improvement over the past 5 years. The WebMicroscope as a didactic tool for laboratory practicals was rated over 8 on a 1-10 scale for basic and systemic pathology and 9/10 for oral pathology especially as various students’ suggestions were implemented. Overall, the quality of the images was rated as very good. Conclusions An overwhelming majority of our students regarded a possibility of using virtual slides at their convenience as highly desirable. Our students and faculty consider the use of the virtual microscope for the study of basic as well as oral pathology as a significant improvement over the light microscope. PMID:21489183

Adequacy of pathology resident training for employment: a survey report from the Future of Pathology Task Group.

PubMed

Kass, Mary E; Crawford, James M; Bennett, Betsy; Cox, Teresa M; Grimes, Margaret M; LiVolsi, Virginia; Fletcher, Christopher D M; Wilkinson, David S

2007-04-01

The recent change in accreditation requirements for anatomic pathology and clinical pathology residency training from 5 to 4 years and the rapid advances in technologies for pathology services have sparked a renewed debate over the adequacy of pathology residency training. In particular, perceived deficiencies in training have been declared from a variety of sources, both in the form of recent editorial opinions and from surveys of community hospital pathologist employers in 1998, 2003, and 2005 by Dr Richard Horowitz. To obtain more comprehensive data on the perceptions of strengths and weaknesses in pathology residency training. The College of American Pathologists conducted a survey of potential pathology employers (senior College of American Pathologists members, members designated as head of group, and members of the Association of Directors of Anatomic and Surgical Pathology). Also surveyed were recent graduates of pathology residency programs, who were identified as being junior members of the College of American Pathologists, were recent recipients of certification from the American Board of Pathology, or were contacted through their directors of pathology residency programs. There were 559 employer respondents, of whom 384 were responsible for hiring and/or supervising new pathologists. There were 247 recent graduates of pathology residency training programs who responded. From the employers' standpoint, the majority expressed overall satisfaction with recent graduates, but almost one third of employers indicated that new hires had a major deficiency in a critical area. Specific areas of deficiency were clinical laboratory management and judgment in ordering special stains and studies. In addition, one half of employers agreed that more guidance and support for newly trained pathologists is needed now than was required 10 years ago. Academic employers generally were more satisfied than private sector employers. Newly trained pathologists did not appear to be inappropriately overconfident in their abilities. In addition, their perceptions of those specific areas in which they are most and least prepared are very similar to the ratings provided by employers. On average, newly trained pathologists' ratings of their own preparedness are highest for specific aspects of general pathology and anatomic pathology, and lowest for specific aspects of clinical pathology and administration. In selecting new pathologists, employers perceived medical knowledge and interpersonal skills as the most important discriminating applicant characteristics. When new employees were asked why they thought they were offered their position, the discriminating qualifications cited most often were academic background and training, as well as completion of a fellowship and subspecialty training. It is our hope that the results of this survey can be used as input for further discussions and recommendations for training of pathology residents so as to further advance the ability of pathologists to provide quality patient care upon their graduation from training.

CAPIRI-IMRT: a phase II study of concurrent capecitabine and irinotecan with intensity-modulated radiation therapy for the treatment of recurrent rectal cancer.

PubMed

Cai, Gang; Zhu, Ji; Palmer, Joshua D; Xu, Ye; Hu, Weigang; Gu, Weilie; Cai, Sanjun; Zhang, Zhen

2015-02-28

This study investigated the local effect and acute toxicity of irinotecan and capecitabine with concurrent intensity-modulated radiation therapy (IMRT) for the treatment of recurrent rectal cancer without prior pelvic irradiation. Seventy-one patients diagnosed with recurrent rectal cancer who did not previously receive pelvic irradiation were treated in our hospital from October 2009 to July 2012. Radiotherapy was delivered to the pelvis, and IMRT of 45 Gy (1.8 Gy per fraction), followed by a boost of 10 Gy to 16 Gy (2 Gy per fraction), was delivered to the recurrent sites. The concurrent chemotherapy regimen was 50 mg/m(2) irinotecan weekly and 625 mg/m(2) capecitabine twice daily (Mon-Fri). Radical surgery was recommended for medically fit patients without extra-pelvic metastases. The patients were followed up every 3 months. Tumor response was evaluated using CT/MRIs according to the RECIST criteria or postoperative pathological findings. NCI-CTC 3.0 was used to score the toxicities. Forty-eight patients (67.6%) had confirmed recurrent rectal cancer without extra pelvic metastases, and 23 patients (32.4%) had extra pelvic metastases. Fourteen patients (19.7%) underwent radical resections (R0) post-chemoradiation. A pathologic complete response was observed in 7 of 14 patients. A clinical complete response was observed in 4 patients (5.6%), and a partial response was observed in 22 patients (31.0%). Only 5 patients (7.0%) showed progressive disease during or shortly after treatment. Of 53 symptomatic patients, clinical complete and partial symptom relief with chemoradiation was achieved in 56.6% and 32.1% of patients, respectively. Only 2 patients (2.8%) experienced grade 4 leukopenia. The most common grade 3 toxicity was diarrhea (16 [22.5%] patients). The median follow-up was 31 months. The cumulative local progression-free survival rate was 74.2% and 33.9% at 1 and 3 years after chemoradiation, respectively. The cumulative total survival rate was 80.1% and 36.5% at 1 and 3 years after chemoradiation, respectively. This study revealed that concurrent irinotecan and capecitabine with IMRT significantly relieves local symptoms and exhibits promising efficacy with manageable toxicities in recurrent rectal cancer without prior pelvic irradiation. Improving the rate of R0 resections will be investigated in a future study.

[Cryptogenic organizing pneumonia].

PubMed

Petitpierre, N; Beigelman, C; Letovanec, I; Lazor, R

2016-10-01

Organizing pneumonia is a particular type of inflammatory reaction of the lung which gives rise to a clinico-pathological syndrome. It is called "secondary" when a cause such as an infection, a drug toxicity, or a connective tissue disease can be identified, or "cryptogenic" when no cause is identified. The clinical picture is usually characterized by the subacute onset of fever, fatigue, cough and dyspnea, with multiple subpleural areas of consolidation on thoracic imaging. Organizing pneumonia is characterised by the presence of buds of endoalveolar connective tissue. These result from an injury to the alveolar epithelium, followed by the deposition of fibrin in the alveolar spaces, and the migration of fibroblasts which produce a myxoid endoalveolar matrix. A remarkable feature of organizing pneumonia is the complete disappearance of these endoalveolar buds with corticosteroid treatment, in sharp contrast with what is seen in pulmonary fibrosis. The clinical response to corticosteroids is usually prompt and excellent. Relapses are frequent but usually benign. As the clinical, imaging and pathological characteristics of organizing pneumonia are now well established, many questions remain unanswered, such as the mechanisms involved in the complete reversibility of the pulmonary lesions, and the role of steroid-sparing treatments such as immunomodulatory macrolides. Copyright © 2015 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Esophageal cancer: outcomes of surgery, neoadjuvant chemotherapy, and three-dimension conformal radiotherapy.

PubMed

Fréchette, Eric; Buck, David A; Kaplan, Brian J; Chung, Theodore D; Shaw, James E; Kachnic, Lisa A; Neifeld, James P

2004-08-01

Neoadjuvant chemotherapy and radiation are being utilized with increasing frequency in the multimodal treatment of esophageal cancer, although their effects on morbidity, mortality, and survival remain unclear. The objective of this study was to determine the outcome of multimodal treatment in patients with localized esophageal cancer treated at a single institution. Between 1995 and 2002, 118 patients underwent treatment for localized esophageal cancer, utilizing surgery alone, chemoradiation alone, or surgery following neoadjuvant chemoradiation. There was no statistically significant difference in morbidity, mortality, or length of stay between the patients who received multimodal therapy when compared to surgery alone. A surgical resection after down-staging was possible in 9 out of 28 patients (32%) with a clinically non-resectable tumor (T4 or M1a). Forty-seven percent of the patients who received neoadjuvant therapy had a complete pathologic response with a 3-year survival of 59% as compared to only 20 months in those patients who did not achieve a complete response (P = 0.037). Neoadjuvant chemotherapy administered concomitantly with conformal radiotherapy can be performed safely in the treatment of esophageal cancer, without increasing the operative morbidity, mortality, or length of stay. The higher complete response rates to neoadjuvant treatment (as compared to other reports) may be due to the use of three-dimensional conformal radiation therapy or the novel use of weekly carboplatin and paclitaxel. Copyright 2004 Wiley-Liss, Inc.

Evaluation of the deposition, translocation and pathological response of brake dust with and without added chrysotile in comparison to crocidolite asbestos following short-term inhalation: Interim results

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

Bernstein, David M., E-mail: davidb@itox.ch; Rogers, Rick, E-mail: rarogers5@yahoo.com; Sepulveda, Rosalina

Chrysotile has been frequently used in the past in manufacturing brakes and continues to be used in brakes in many countries. This study was designed to provide an understanding of the biokinetics and potential toxicology following inhalation of brake dust following short term exposure in rats. The deposition, translocation and pathological response of brake dust derived from brake pads manufactured with chrysotile were evaluated in comparison to the amphibole, crocidolite asbestos. Rats were exposed by inhalation 6 h/day for 5 days to either brake dust obtained by sanding of brake-drums manufactured with chrysotile, a mixture of chrysotile and the brakemore » dust or crocidolite asbestos. No significant pathological response was observed at any time point in either the brake dust or chrysotile/brake dust exposure groups. The long chrysotile fibers (> 20 μm) cleared quickly with T{sub 1/2} estimated as 30 and 33 days, respectively in the brake dust and the chrysotile/brake dust exposure groups. In contrast, the long crocidolite fibers had a T{sub 1/2} > 1000 days and initiated a rapid inflammatory response in the lung following exposure resulting in a 5-fold increase in fibrotic response within 91 days. These results provide support that brake dust derived from chrysotile containing brake drums would not initiate a pathological response in the lung following short term inhalation. - Highlights: • We evaluated brake dust w/wo added chrysotile in comparison to crocidolite asbestos. • Persistence, translocation, pathological response in the lung and pleural cavity. • Chrysotile cleared rapidly from the lung while the crocidolite asbestos persisted. • No significant pathology observed at any time point in the brake-dust groups. • Crocidolite produced pathological response - Wagner 4 interstitial fibrosis by 32d.« less

Chronic pancreatitis.

PubMed

Kleeff, Jorg; Whitcomb, David C; Shimosegawa, Tooru; Esposito, Irene; Lerch, Markus M; Gress, Thomas; Mayerle, Julia; Drewes, Asbjørn Mohr; Rebours, Vinciane; Akisik, Fatih; Muñoz, J Enrique Domínguez; Neoptolemos, John P

2017-09-07

Chronic pancreatitis is defined as a pathological fibro-inflammatory syndrome of the pancreas in individuals with genetic, environmental and/or other risk factors who develop persistent pathological responses to parenchymal injury or stress. Potential causes can include toxic factors (such as alcohol or smoking), metabolic abnormalities, idiopathic mechanisms, genetics, autoimmune responses and obstructive mechanisms. The pathophysiology of chronic pancreatitis is fairly complex and includes acinar cell injury, acinar stress responses, duct dysfunction, persistent or altered inflammation, and/or neuro-immune crosstalk, but these mechanisms are not completely understood. Chronic pancreatitis is characterized by ongoing inflammation of the pancreas that results in progressive loss of the endocrine and exocrine compartment owing to atrophy and/or replacement with fibrotic tissue. Functional consequences include recurrent or constant abdominal pain, diabetes mellitus (endocrine insufficiency) and maldigestion (exocrine insufficiency). Diagnosing early-stage chronic pancreatitis is challenging as changes are subtle, ill-defined and overlap those of other disorders. Later stages are characterized by variable fibrosis and calcification of the pancreatic parenchyma; dilatation, distortion and stricturing of the pancreatic ducts; pseudocysts; intrapancreatic bile duct stricturing; narrowing of the duodenum; and superior mesenteric, portal and/or splenic vein thrombosis. Treatment options comprise medical, radiological, endoscopic and surgical interventions, but evidence-based approaches are limited. This Primer highlights the major progress that has been made in understanding the pathophysiology, presentation, prevalence and management of chronic pancreatitis and its complications.

Gasdermin B expression predicts poor clinical outcome in HER2-positive breast cancer

PubMed Central

Hergueta-Redondo, Marta; Sarrio, David; Molina-Crespo, Ángela; Vicario, Rocío; Bernadó-Morales, Cristina; Martínez, Lidia; Rojo-Sebastián, Alejandro; Serra-Musach, Jordi; Mota, Alba; Martínez-Ramírez, Ángel; Castilla, Maria Ángeles; González-Martin, Antonio; Pernas, Sonia; Cano, Amparo; Cortes, Javier; Nuciforo, Paolo G.; Peg, Vicente; Palacios, José; Pujana, Miguel Ángel; Arribas, Joaquín; Moreno-Bueno, Gema

2016-01-01

Around, 30–40% of HER2-positive breast cancers do not show substantial clinical benefit from the targeted therapy and, thus, the mechanisms underlying resistance remain partially unknown. Interestingly, ERBB2 is frequently co-amplified and co-expressed with neighbour genes that may play a relevant role in this cancer subtype. Here, using an in silico analysis of data from 2,096 breast tumours, we reveal a significant correlation between Gasdermin B (GSDMB) gene (located 175 kilo bases distal from ERBB2) expression and the pathological and clinical parameters of poor prognosis in HER2-positive breast cancer. Next, the analysis of three independent cohorts (totalizing 286 tumours) showed that approximately 65% of the HER2-positive cases have GSDMB gene amplification and protein over-expression. Moreover, GSDMB expression was also linked to poor therapeutic responses in terms of lower relapse free survival and pathologic complete response as well as positive lymph node status and the development of distant metastasis under neoadjuvant and adjuvant treatment settings, respectively. Importantly, GSDMB expression promotes survival to trastuzumab in different HER2-positive breast carcinoma cells, and is associated with trastuzumab resistance phenotype in vivo in Patient Derived Xenografts. In summary, our data identifies the ERBB2 co-amplified and co-expressed gene GSDMB as a critical determinant of poor prognosis and therapeutic response in HER2-positive breast cancer. PMID:27462779

Gasdermin B expression predicts poor clinical outcome in HER2-positive breast cancer.

PubMed

Hergueta-Redondo, Marta; Sarrio, David; Molina-Crespo, Ángela; Vicario, Rocío; Bernadó-Morales, Cristina; Martínez, Lidia; Rojo-Sebastián, Alejandro; Serra-Musach, Jordi; Mota, Alba; Martínez-Ramírez, Ángel; Castilla, Mª Ángeles; González-Martin, Antonio; Pernas, Sonia; Cano, Amparo; Cortes, Javier; Nuciforo, Paolo G; Peg, Vicente; Palacios, José; Pujana, Miguel Ángel; Arribas, Joaquín; Moreno-Bueno, Gema

2016-08-30

Around, 30-40% of HER2-positive breast cancers do not show substantial clinical benefit from the targeted therapy and, thus, the mechanisms underlying resistance remain partially unknown. Interestingly, ERBB2 is frequently co-amplified and co-expressed with neighbour genes that may play a relevant role in this cancer subtype. Here, using an in silico analysis of data from 2,096 breast tumours, we reveal a significant correlation between Gasdermin B (GSDMB) gene (located 175 kilo bases distal from ERBB2) expression and the pathological and clinical parameters of poor prognosis in HER2-positive breast cancer. Next, the analysis of three independent cohorts (totalizing 286 tumours) showed that approximately 65% of the HER2-positive cases have GSDMB gene amplification and protein over-expression. Moreover, GSDMB expression was also linked to poor therapeutic responses in terms of lower relapse free survival and pathologic complete response as well as positive lymph node status and the development of distant metastasis under neoadjuvant and adjuvant treatment settings, respectively. Importantly, GSDMB expression promotes survival to trastuzumab in different HER2-positive breast carcinoma cells, and is associated with trastuzumab resistance phenotype in vivo in Patient Derived Xenografts. In summary, our data identifies the ERBB2 co-amplified and co-expressed gene GSDMB as a critical determinant of poor prognosis and therapeutic response in HER2-positive breast cancer.

Targeted Androgen Pathway Suppression in Localized Prostate Cancer: A Pilot Study

PubMed Central

Mostaghel, Elahe A.; Nelson, Peter S.; Lange, Paul; Lin, Daniel W.; Taplin, Mary Ellen; Balk, Steven; Ellis, William; Kantoff, Philip; Marck, Brett; Tamae, Daniel; Matsumoto, Alvin M.; True, Lawrence D.; Vessella, Robert; Penning, Trevor; Hunter Merrill, Rachel; Gulati, Roman; Montgomery, Bruce

2014-01-01

Purpose Ligand-mediated activation of the androgen receptor (AR) is critical for prostate cancer (PCa) survival and proliferation. The failure to completely ablate tissue androgens may limit suppression of PCa growth. We evaluated combinations of CYP17A and 5-α-reductase inhibitors for reducing prostate androgen levels, AR signaling, and PCa volumes. Patients and Methods Thirty-five men with intermediate/high-risk clinically localized PCa were randomly assigned to goserelin combined with dutasteride (ZD), bicalutamide and dutasteride (ZBD), or bicalutamide, dutasteride, and ketoconazole (ZBDK) for 3 months before prostatectomy. Controls included patients receiving combined androgen blockade with luteinizing hormone-releasing hormone agonist and bicalutamide. The primary outcome measure was tissue dihydrotestosterone (DHT) concentration. Results Prostate DHT levels were substantially lower in all experimental arms (0.02 to 0.04 ng/g v 0.92 ng/g in controls; P < .001). The ZBDK group demonstrated the greatest percentage decline in serum testosterone, androsterone, and dehydroepiandrosterone sulfate (P < .05 for all). Staining for AR and the androgen-regulated genes prostate-specific antigen and TMPRSS2 was strongly suppressed in benign glands and moderately in malignant glands (P < .05 for all). Two patients had pathologic complete response, and nine had ≤ 0.2 cm3 of residual tumor (defined as a near-complete response), with the largest numbers of complete and near-complete responses in the ZBDK group. Conclusion Addition of androgen synthesis inhibitors lowers prostate androgens below that achieved with standard therapy, but significant AR signaling remains. Tissue-based analysis of steroids and AR signaling is critical to informing the search for optimal local and systemic control of high-risk prostate cancer. PMID:24323034

Prevention of the Post-traumatic Fibrotic Response in Joints

DTIC Science & Technology

2014-10-01

The American journal of forensic medicine and pathology . 1988; 9(4):310-2. 14 APPENDICES: An abstract submitted for the ORS conference...clinical problem of posttraumatic joint stiffness, a pathology that reduces the range of motion (ROM) of injured joints and contributes to the...development of osteoarthritis. The fundamental hypothesis that drives the current study is that pathological fibrotic response of injured joint tissues

Arthroscopic findings of a diagnostic dilemma- hip pathology with normal imaging.

PubMed

Buikstra, Joel Glenn; Fary, Camdon; Tran, Phong

2017-03-21

Patients with groin, hip and pelvic pain but normal findings on MRI and minimal changes on x-ray can be a diagnostic problem. This paper looks at the arthroscopic findings of patients who have had hip pain and a positive response to an intra-articular anaesthetic but have non-contributory imaging. We hypothesized that standard MRI's were missing significant pathology and if there was a response to intra-articular local anaesthesia, pathology found during arthroscopy was likely. A retrospective review of all hip arthroscopies performed from March 2011 to January 2015 by two orthopaedic surgeons specializing in hip arthroscopy was conducted to identify patients with clinically suspected intra-articular hip pathology despite a normal MRI report and X-ray. Clinical suspicion of intra-articular hip pathology was confirmed with a positive response to a fluoroscopically guided intra-articular injection of local anaesthetic and corticosteroid. Pathologic findings were collated from the standardised operative notes. Fifty-three hip arthroscopies performed in 51 patients met the inclusion criteria from a total of 1348 hip arthroscopies performed over a 46-month period. All but one of the 53 (98%) hips had arthroscopically confirmed pathology. Mean patient age was 32.5 years [15 to 67 years] with 40 (78%) females and 11 (22%) males. 92.5% of the hips (49/53) were FADIR (flexion, adduction and internal rotation) positive on clinical examination, giving this test a positive predictive value of 98% (95% CI: 89.31 to 99.67%) for intra-articular pathology. In patients with a normal MRI without contrast and a positive response (relief of pain) to an intra-articular injection that failed conservative management, there is a 98% chance of intra-articular hip pathology being discovered on hip arthroscopy.

Tumor response evaluation after neoadjuvant chemotherapy in locally advanced gastric adenocarcinoma: a prospective, multi-center cohort study

PubMed Central

De Martini, Paolo; Ceresoli, Marco; Mari, Giulio M.; Costanzi, Andrea; Maggioni, Dario; Pugliese, Raffaele; Ferrari, Giovanni

2017-01-01

Background To verify the prognostic value of the pathologic and radiological tumor response after neoadjuvant chemotherapy in the treatment of locally advanced gastric adenocarcinoma. Methods A total of 67 patients with locally advanced gastric cancer (clinical ≥ T2 or nodal disease and without evidence of distant metastases) underwent perioperative chemotherapy (ECF or ECX regimen) from December 2009 through June 2015 in two surgical units. Histopathological and radiological response to chemotherapy were evaluated by using tumor regression grade (TRG) (Becker’s criteria) and volume change assessed by CT. Results Fifty-one (86%) patients completed all chemotherapy scheduled cycles successfully and surgery was curative (R0) in 64 (97%) subjects. The histopathological analysis showed 19 (29%) specimens with TRG1 (less than 10% of vital tumor left) and 25 (37%) patients had partial or complete response (CR) assessed by CT scan. Median disease free survival (DFS) and overall survival (OS) were 25.70 months (range, 14.52–36.80 months) and 36.60 months (range, 24.3–52.9 months), respectively. The median follow up was 27 months (range, 5.00–68.00 months). Radiological response and TRG were found to be a prognostic factor for OS and DFS, while tumor histology was not significantly related to survival. Conclusions Both radiological response and TRG have been shown as promising survival markers in patients treated with perioperative chemotherapy for locally advanced gastric cancer. Other predictive markers of response to chemotherapy are strongly required. PMID:29299362

Validating Laboratory Results in Electronic Health Records

PubMed Central

Perrotta, Peter L.; Karcher, Donald S.

2017-01-01

Context Laboratories must ensure that the test results and pathology reports they transmit to a patient’s electronic health record (EHR) are accurate, complete, and presented in a useable format. Objective To determine the accuracy, completeness, and formatting of laboratory test results and pathology reports transmitted from the laboratory to the EHR. Design Participants from 45 institutions retrospectively reviewed results from 16 different laboratory tests, including clinical and anatomic pathology results, within the EHR used by their providers to view laboratory results. Results were evaluated for accuracy, presence of required elements, and usability. Both normal and abnormal results were reviewed for tests, some of which were performed in-house and others at a reference laboratory. Results Overall accuracy for test results transmitted to the EHR was greater than 99.3% (1052 of 1059). There was lower compliance for completeness of test results, with 69.6% (732 of 1051) of the test results containing all essential reporting elements. Institutions that had fewer than half of their orders entered electronically had lower test result completeness rates. The rate of appropriate formatting of results was 90.9% (98 of 1010). Conclusions The great majority of test results are accurately transmitted from the laboratory to the EHR; however, lower percentages are transmitted completely and in a useable format. Laboratories should verify the accuracy, completeness, and format of test results at the time of test implementation, after test changes, and periodically. PMID:27575266

Spontaneous correction of pathologic tooth migration and reduced infrabony pockets following nonsurgical periodontal therapy: a case report.

PubMed

Sato, Shuichi; Ujiie, Hisashi; Ito, Koichi

2004-10-01

This case report describes the spontaneous correction of pathologic tooth migration and reduced infrabony pockets after nonsurgical periodontal therapy. A 3-mm diastema between the maxillary incisors was closed completely, and the mandibular teeth, which had migrated pathologically, returned to the optimal position. Clinical evaluation showed a significant reduction in probing depth, with increased clinical attachment and bone deposition demonstrated radiologically.

RAS mutations predict radiologic and pathologic response in patients treated with chemotherapy prior to resection of colorectal liver metastases

PubMed Central

Mise, Yoshihiro; Kopetz, Scott; Loyer, Evelyne M.; Andreou, Andreas; Cooper, Amanda B.; Kaur, Harmeet; Aloia, Thomas A.; Maru, Dipen M.; Vauthey, Jean-Nicolas

2014-01-01

Purpose RAS mutations have been reported to be a potential prognostic factor in patients with colorectal liver metastases (CLM). However, the impact of RAS mutations on response to chemotherapy remains unclear. We sought to determine the association between RAS mutations and response to preoperative chemotherapy and their impact on survival in patients undergoing curative resection of CLM. Methods RAS mutational status was assessed and its relation to morphologic response and pathologic response was investigated in 184 patients meeting inclusion criteria. Predictors of survival were assessed. The prognostic impact of RAS mutational status was then analyzed using two different multivariate models including either radiologic morphologic response (model 1) or pathologic response (model 2). Results Optimal morphologic response and major pathologic response were more common in patients with wild-type RAS (32.9% and 58.9%, respectively) than in patients with RAS mutations (10.5% and 36.8%; P =.006 and .015, respectively). Multivariate analysis confirmed that wild-type RAS was a strong predictor of optimal morphologic response (odds ratio [OR], 4.38; 95% CI, 1.45-13.2) and major pathologic response (OR,2.79; 95% CI, 1.29-6.04). RAS mutations were independently correlated with both overall survival and recurrence free-survival (hazard ratios, 3.25 and 2.02, respectively, in model 1, and 3.19 and 2.23, respectively, in model 2). Subanalysis revealed that RAS mutational status clearly stratified prognosis in patients with inadequate response to preoperative chemotherapy. Conclusion RAS mutational status can be used to complement the current prognostic indicators for patients undergoing curative resection of CLM after preoperative modern chemotherapy. PMID:25227306

RAS mutations predict radiologic and pathologic response in patients treated with chemotherapy before resection of colorectal liver metastases.

PubMed

Zimmitti, Giuseppe; Shindoh, Junichi; Mise, Yoshihiro; Kopetz, Scott; Loyer, Evelyne M; Andreou, Andreas; Cooper, Amanda B; Kaur, Harmeet; Aloia, Thomas A; Maru, Dipen M; Vauthey, Jean-Nicolas

2015-03-01

RAS mutations have been reported to be a potential prognostic factor in patients with colorectal liver metastases (CLM). However, the impact of RAS mutations on response to chemotherapy remains unclear. The purpose of this study was to investigate the correlation between RAS mutations and response to preoperative chemotherapy and their impact on survival in patients undergoing curative resection of CLM. RAS mutational status was assessed and its relation to morphologic response and pathologic response was investigated in 184 patients meeting inclusion criteria. Predictors of survival were assessed. The prognostic impact of RAS mutational status was then analyzed using two different multivariate models, including either radiologic morphologic response (model 1) or pathologic response (model 2). Optimal morphologic response and major pathologic response were more common in patients with wild-type RAS (32.9 and 58.9%, respectively) than in patients with RAS mutations (10.5 and 36.8%; P = 0.006 and 0.015, respectively). Multivariate analysis confirmed that wild-type RAS was a strong predictor of optimal morphologic response [odds ratio (OR), 4.38; 95% CI 1.45-13.15] and major pathologic response (OR, 2.61; 95% CI 1.17-5.80). RAS mutations were independently correlated with both overall survival and recurrence free-survival (hazard ratios, 3.57 and 2.30, respectively, in model 1, and 3.19 and 2.09, respectively, in model 2). Subanalysis revealed that RAS mutational status clearly stratified survival in patients with inadequate response to preoperative chemotherapy. RAS mutational status can be used to complement the current prognostic indicators for patients undergoing curative resection of CLM after preoperative modern chemotherapy.

Lymphocyte density determined by computational pathology validated as a predictor of response to neoadjuvant chemotherapy in breast cancer: secondary analysis of the ARTemis trial.

PubMed

Ali, H R; Dariush, A; Thomas, J; Provenzano, E; Dunn, J; Hiller, L; Vallier, A-L; Abraham, J; Piper, T; Bartlett, J M S; Cameron, D A; Hayward, L; Brenton, J D; Pharoah, P D P; Irwin, M J; Walton, N A; Earl, H M; Caldas, C

2017-08-01

We have previously shown lymphocyte density, measured using computational pathology, is associated with pathological complete response (pCR) in breast cancer. The clinical validity of this finding in independent studies, among patients receiving different chemotherapy, is unknown. The ARTemis trial randomly assigned 800 women with early stage breast cancer between May 2009 and January 2013 to three cycles of docetaxel, followed by three cycles of fluorouracil, epirubicin and cyclophosphamide once every 21 days with or without four cycles of bevacizumab. The primary endpoint was pCR (absence of invasive cancer in the breast and lymph nodes). We quantified lymphocyte density within haematoxylin and eosin (H&E) whole slide images using our previously described computational pathology approach: for every detected lymphocyte the average distance to the nearest 50 lymphocytes was calculated and the density derived from this statistic. We analyzed both pre-treatment biopsies and post-treatment surgical samples of the tumour bed. Of the 781 patients originally included in the primary endpoint analysis of the trial, 609 (78%) were included for baseline lymphocyte density analyses and a subset of 383 (49% of 781) for analyses of change in lymphocyte density. The main reason for loss of patients was the availability of digitized whole slide images. Pre-treatment lymphocyte density modelled as a continuous variable was associated with pCR on univariate analysis (odds ratio [OR], 2.92; 95% CI, 1.78-4.85; P < 0.001) and after adjustment for clinical covariates (OR, 2.13; 95% CI, 1.24-3.67; P = 0.006). Increased pre- to post-treatment lymphocyte density showed an independent inverse association with pCR (adjusted OR, 0.1; 95% CI, 0.033-0.31; P < 0.001). Lymphocyte density in pre-treatment biopsies was validated as an independent predictor of pCR in breast cancer. Computational pathology is emerging as a viable and objective means of identifying predictive biomarkers for cancer patients. NCT01093235. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

Invertebrate Models for Coenzyme Q10 Deficiency

PubMed Central

Fernández-Ayala, Daniel J.M.; Jiménez-Gancedo, Sandra; Guerra, Ignacio; Navas, Plácido

2014-01-01

The human syndrome of coenzyme Q (CoQ) deficiency is a heterogeneous mitochondrial disease characterized by a diminution of CoQ content in cells and tissues that affects all the electron transport processes CoQ is responsible for, like the electron transference in mitochondria for respiration and ATP production and the antioxidant capacity that it exerts in membranes and lipoproteins. Supplementation with external CoQ is the main attempt to address these pathologies, but quite variable results have been obtained ranging from little response to a dramatic recovery. Here, we present the importance of modeling human CoQ deficiencies in animal models to understand the genetics and the pathology of this disease, although the election of an organism is crucial and can sometimes be controversial. Bacteria and yeast harboring mutations that lead to CoQ deficiency are unable to grow if they have to respire but develop without any problems on media with fermentable carbon sources. The complete lack of CoQ in mammals causes embryonic lethality, whereas other mutations produce tissue-specific diseases as in humans. However, working with transgenic mammals is time and cost intensive, with no assurance of obtaining results. Caenorhabditis elegans and Drosophila melanogaster have been used for years as organisms to study embryonic development, biogenesis, degenerative pathologies, and aging because of the genetic facilities and the speed of working with these animal models. In this review, we summarize several attempts to model reliable human CoQ deficiencies in invertebrates, focusing on mutant phenotypes pretty similar to those observed in human patients. PMID:25126050

Capecitabine Initially Concomitant to Radiotherapy Then Perioperatively Administered in Locally Advanced Rectal Cancer

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

Zampino, Maria Giulia; Magni, Elena; Leonardi, Maria Cristina

2009-10-01

Purpose: To evaluate the impact of neoadjuvant capecitabine, concomitant to radiotherapy, followed by capecitabine monotherapy, in operable locally advanced rectal cancer (LARC) by measuring pathologic response and conservative surgery rate, toxicity profile, and disease-free survival (DFS). Methods and Materials: From October 2002 to July 2006, a total of 51 patients affected by LARC (T3-T4 or any node positive tumor), received capecitabine (825 mg/m{sup 2}, orally, twice daily continuously) concomitant to radiotherapy on the pelvis (50.4 Gy/ 28 fractions), followed by two cycles of capecitabine (1,250 mg/m{sup 2}, orally, twice daily, 14 days on 7 days off) up until 2 weeksmore » before surgery. Tailored adjuvant systemic treatment was discussed according to pathologic stage. Results: Of 51 patients, (median age 61 years, range 38-82 years; 19 women and 32 men; ECOG performance status 0/1/2: 46/4/1), 50 were evaluable for response: 18% complete pathologic remission; 12% T-downstaging, and 30% N-downstaging. One patient died before surgery from mesenteric stroke. Grade 3 acute toxicities were 2% diarrhea, 8% dermatitis, 2% liver function test elevation, and 2% hand-foot syndrome. Sphincter preservation rates for tumors {<=}6 cm from the anal verge were 62% and 80% for the whole population. Median follow up was 43.0 months (range 0.8-68.6 months). Five-years DFS was 85.4% (95% CI = 75.3-95.4%). Conclusions: Based on our study results, we conclude that this regimen is well tolerated and active and compares favorably with existing capecitabine-based approaches.« less

Neoadjuvant chemotherapy in breast cancer: prediction of pathologic response with PET/CT and dynamic contrast-enhanced MR imaging--prospective assessment.

PubMed

Tateishi, Ukihide; Miyake, Mototaka; Nagaoka, Tomoaki; Terauchi, Takashi; Kubota, Kazunori; Kinoshita, Takayuki; Daisaki, Hiromitsu; Macapinlac, Homer A

2012-04-01

To clarify whether fluorine 18 ((18)F) fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) and dynamic contrast-enhanced (DCE) magnetic resonance (MR) imaging performed after two cycles of neoadjuvant chemotherapy (NAC) can be used to predict pathologic response in breast cancer. Institutional human research committee approval and written informed consent were obtained. Accuracy after two cycles of NAC for predicting pathologic complete response (pCR) was examined in 142 women (mean age, 57 years: range, 43-72 years) with histologically proved breast cancer between December 2005 and February 2009. Quantitative PET/CT and DCE MR imaging were performed at baseline and after two cycles of NAC. Parameters of PET/CT and of blood flow and microvascular permeability at DCE MR were compared with pathologic response. Patients were also evaluated after NAC by using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 based on DCE MR measurements and European Organization for Research and Treatment of Cancer (EORTC) criteria and PET Response Criteria in Solid Tumors (PERCIST) 1.0 based on PET/CT measurements. Multiple logistic regression analyses were performed to examine continuous variables at PET/CT and DCE MR to predict pCR, and diagnostic accuracies were compared with the McNemar test. Significant decrease from baseline of all parameters at PET/CT and DCE MR was observed after NAC. Therapeutic response was obtained in 24 patients (17%) with pCR and 118 (83%) without pCR. Sensitivity, specificity, and accuracy to predict pCR were 45.5%, 85.5%, and 82.4%, respectively, with RECIST and 70.4%, 95.7%, and 90.8%, respectively, with EORTC and PERCIST. Multiple logistic regression revealed three significant independent predictors of pCR: percentage maximum standardized uptake value (%SUV(max)) (odds ratio [OR], 1.22; 95% confidence interval [CI]: 1.11, 1.34; P < .0001), percentage rate constant (%k(ep)) (OR, 1.07; CI: 1.03, 1.12; P = .002), and percentage area under the time-intensity curve over 90 seconds (%AUC(90)) (OR, 1.04; CI: 1.01, 1.07; P = .048). When diagnostic accuracies are compared, PET/CT is superior to DCE MR for the prediction of pCR (%SUV(max) [90.1%] vs %κ(ep) [83.8%] or %AUC(90) [76.8%]; P < .05). The sensitivities of %SUV(max) (66.7%), %k(ep) (51.7%), and %AUC(90) (50.0%) at (18)F-FDG PET/CT and DCE MR after two cycles of NAC are not acceptable, but the specificities (96.4%, 92.0%, and 95.2%, respectively) are high for stratification of pCR cases in breast cancer. © RSNA, 2012.

From normal fear to pathological anxiety.

PubMed

Rosen, J B; Schulkin, J

1998-04-01

In this article the authors address how pathological anxiety may develop from adaptive fear states. Fear responses (e.g., freezing, startle, heart rate and blood pressure changes, and increased vigilance) are functionally adaptive behavioral and perceptual responses elicited during danger to facilitate appropriate defensive responses that can reduce danger or injury (e.g., escape and avoidance). Fear is a central motive state of action tendencies subserved by fear circuits, with the amygdala playing a central role. Pathological anxiety is conceptualized as an exaggerated fear state in which hyperexcitability of fear circuits that include the amygdala and extended amygdala (i.e., bed nucleus of the stria terminalis) is expressed as hypervigilance and increased behavioral responsivity to fearful stimuli. Reduced thresholds for activation and hyperexcitability in fear circuits develop through sensitization- or kindling-like processes that involve neuropeptides, hormones, and other proteins. Hyperexcitability in fear circuits is expressed as pathological anxiety that is manifested in the various anxiety disorders.

Mechanisms of physiological and pathological cardiac hypertrophy.

PubMed

Nakamura, Michinari; Sadoshima, Junichi

2018-04-19

Cardiomyocytes exit the cell cycle and become terminally differentiated soon after birth. Therefore, in the adult heart, instead of an increase in cardiomyocyte number, individual cardiomyocytes increase in size, and the heart develops hypertrophy to reduce ventricular wall stress and maintain function and efficiency in response to an increased workload. There are two types of hypertrophy: physiological and pathological. Hypertrophy initially develops as an adaptive response to physiological and pathological stimuli, but pathological hypertrophy generally progresses to heart failure. Each form of hypertrophy is regulated by distinct cellular signalling pathways. In the past decade, a growing number of studies have suggested that previously unrecognized mechanisms, including cellular metabolism, proliferation, non-coding RNAs, immune responses, translational regulation, and epigenetic modifications, positively or negatively regulate cardiac hypertrophy. In this Review, we summarize the underlying molecular mechanisms of physiological and pathological hypertrophy, with a particular emphasis on the role of metabolic remodelling in both forms of cardiac hypertrophy, and we discuss how the current knowledge on cardiac hypertrophy can be applied to develop novel therapeutic strategies to prevent or reverse pathological hypertrophy.

Prevention of the Post-traumatic Fibrotic Response in Joints

DTIC Science & Technology

2014-10-01

JJ, Wolman M. Aging of wound healing in an experimental model in mice. The American journal of forensic medicine and pathology . 1988; 9(4):310-2...SUPPLEMENTARY NOTES 14. ABSTRACT The ongoing study addresses the critical clinical problem of posttraumatic joint stiffness, a pathology that reduces...study is that pathological fibrotic response of injured joint tissues may be limited by targeting the formation of collagen fibrils, a main component

Exquisite sensitivity of TP53 mutant and basal breast cancers to a dose-dense epirubicin-cyclophosphamide regimen.

PubMed

Bertheau, Philippe; Turpin, Elisabeth; Rickman, David S; Espié, Marc; de Reyniès, Aurélien; Feugeas, Jean-Paul; Plassa, Louis-François; Soliman, Hany; Varna, Mariana; de Roquancourt, Anne; Lehmann-Che, Jacqueline; Beuzard, Yves; Marty, Michel; Misset, Jean-Louis; Janin, Anne; de Thé, Hugues

2007-03-01

In breast cancers, only a minority of patients fully benefit from the different chemotherapy regimens currently in use. Identification of markers that could predict the response to a particular regimen would thus be critically important for patient care. In cell lines or animal models, tumor protein p53 (TP53) plays a critical role in modulating the response to genotoxic drugs. TP53 is activated in response to DNA damage and triggers either apoptosis or cell-cycle arrest, which have opposite effects on cell fate. Yet, studies linking TP53 status and chemotherapy response have so far failed to unambiguously establish this paradigm in patients. Breast cancers with a TP53 mutation were repeatedly shown to have a poor outcome, but whether this reflects poor response to treatment or greater intrinsic aggressiveness of the tumor is unknown. In this study we analyzed 80 noninflammatory breast cancers treated by frontline (neoadjuvant) chemotherapy. Tumor diagnoses were performed on pretreatment biopsies, and the patients then received six cycles of a dose-dense regimen of 75 mg/m(2) epirubicin and 1,200 mg/m(2) cyclophosphamide, given every 14 days. After completion of chemotherapy, all patients underwent mastectomies, thus allowing for a reliable assessment of chemotherapy response. The pretreatment biopsy samples were used to determine the TP53 status through a highly efficient yeast functional assay and to perform RNA profiling. All 15 complete responses occurred among the 28 TP53-mutant tumors. Furthermore, among the TP53-mutant tumors, nine out of ten of the highly aggressive basal subtypes (defined by basal cytokeratin [KRT] immunohistochemical staining) experienced complete pathological responses, and only TP53 status and basal subtype were independent predictors of a complete response. Expression analysis identified many mutant TP53-associated genes, including CDC20, TTK, CDKN2A, and the stem cell gene PROM1, but failed to identify a transcriptional profile associated with complete responses among TP53 mutant tumors. In patients with unresponsive tumors, mutant TP53 status predicted significantly shorter overall survival. The 15 patients with responsive TP53-mutant tumors, however, had a favorable outcome, suggesting that this chemotherapy regimen can overcome the poor prognosis generally associated with mutant TP53 status. This study demonstrates that, in noninflammatory breast cancers, TP53 status is a key predictive factor for response to this dose-dense epirubicin-cyclophosphamide regimen and further suggests that the basal subtype is exquisitely sensitive to this association. Given the well-established predictive value of complete responses for long-term survival and the poor prognosis of basal and TP53-mutant tumors treated with other regimens, this chemotherapy could be particularly suited for breast cancer patients with a mutant TP53, particularly those with basal features.

[Cytomixis, its nature, significance and the cytological consequences].

PubMed

Kravets, E A

2012-01-01

Cytomixis is the widespread natural process of intercellular interaction which is characteristic for vegetative and generative tissues in both normal and pathological conditions. The origin significance and genetic control cytomixis still remain not completely clear. The popularity of view of the pathological nature of cytomixis based on its peculiar plants with genetic instability and impaired homeostasis. In the genetic control of cytomixis seem to be involved meiotic genes which are responsible for segregation and organization of chromosomes. Their activity is modified by environmental factors through signal transduction. It is assumed via cytomixis, from one side, the informational contact can be reached and meiosis and gametogenesis are synchronized, with another, increase of the genetic variety and level of the heterozygosis of microsporocytes. The activity of cytomixis varies over wide limits. The greatest influence on its activity have mutagenesis hybridization and polyploidy. In this context cytomixis can fulfill the function of cell selection which is activated by exceeding of the threshold level of the microsporocyte damages (or genetical disbalance).

How host regulation of Helicobacter pylori-induced gastritis protects against peptic ulcer disease and gastric cancer.

PubMed

Dhar, Poshmaal; Ng, Garrett Z; Sutton, Philip

2016-09-01

The bacterial pathogen Helicobacter pylori is the etiological agent of a range of gastrointestinal pathologies including peptic ulcer disease and the major killer, gastric adenocarcinoma. Infection with this bacterium induces a chronic inflammatory response in the gastric mucosa (gastritis). It is this gastritis that, over decades, eventually drives the development of H. pylori-associated disease in some individuals. The majority of studies investigating H. pylori pathogenesis have focused on factors that promote disease development in infected individuals. However, an estimated 85% of those infected with H. pylori remain completely asymptomatic, despite the presence of pathogenic bacteria that drive a chronic gastritis that lasts many decades. This indicates the presence of highly effective regulatory processes in the host that, in most cases, keeps a check on inflammation and protect against disease. In this minireview we discuss such known host factors and how they prevent the development of H. pylori-associated pathologies. Copyright © 2016 the American Physiological Society.

Simultaneous submicrometric 3D imaging of the micro-vascular network and the neuronal system in a mouse spinal cord

PubMed Central

Fratini, Michela; Bukreeva, Inna; Campi, Gaetano; Brun, Francesco; Tromba, Giuliana; Modregger, Peter; Bucci, Domenico; Battaglia, Giuseppe; Spanò, Raffaele; Mastrogiacomo, Maddalena; Requardt, Herwig; Giove, Federico; Bravin, Alberto; Cedola, Alessia

2015-01-01

Faults in vascular (VN) and neuronal networks of spinal cord are responsible for serious neurodegenerative pathologies. Because of inadequate investigation tools, the lacking knowledge of the complete fine structure of VN and neuronal system represents a crucial problem. Conventional 2D imaging yields incomplete spatial coverage leading to possible data misinterpretation, whereas standard 3D computed tomography imaging achieves insufficient resolution and contrast. We show that X-ray high-resolution phase-contrast tomography allows the simultaneous visualization of three-dimensional VN and neuronal systems of ex-vivo mouse spinal cord at scales spanning from millimeters to hundreds of nanometers, with nor contrast agent nor sectioning and neither destructive sample-preparation. We image both the 3D distribution of micro-capillary network and the micrometric nerve fibers, axon-bundles and neuron soma. Our approach is very suitable for pre-clinical investigation of neurodegenerative pathologies and spinal-cord-injuries, in particular to resolve the entangled relationship between VN and neuronal system. PMID:25686728

Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes.

PubMed

von Minckwitz, Gunter; Untch, Michael; Blohmer, Jens-Uwe; Costa, Serban D; Eidtmann, Holger; Fasching, Peter A; Gerber, Bernd; Eiermann, Wolfgang; Hilfrich, Jörn; Huober, Jens; Jackisch, Christian; Kaufmann, Manfred; Konecny, Gottfried E; Denkert, Carsten; Nekljudova, Valentina; Mehta, Keyur; Loibl, Sibylle

2012-05-20

The exact definition of pathologic complete response (pCR) and its prognostic impact on survival in intrinsic breast cancer subtypes is uncertain. Tumor response at surgery and its association with long-term outcome of 6,377 patients with primary breast cancer receiving neoadjuvant anthracycline-taxane-based chemotherapy in seven randomized trials were analyzed. Disease-free survival (DFS) was significantly superior in patients with no invasive and no in situ residuals in breast or nodes (n = 955) compared with patients with residual ductal carcinoma in situ only (n = 309), no invasive residuals in breast but involved nodes (n = 186), only focal-invasive disease in the breast (n = 478), and gross invasive residual disease (n = 4,449; P < .001). Hazard ratios for DFS comparing patients with or without pCR were lowest when defined as no invasive and no in situ residuals (0.446) and increased monotonously when in situ residuals (0.523), no invasive breast residuals but involved nodes (0.623), and focal-invasive disease (0.727) were included in the definition. pCR was associated with improved DFS in luminal B/human epidermal growth factor receptor 2 (HER2) -negative (P = .005), HER2-positive/nonluminal (P < .001), and triple-negative (P < .001) tumors but not in luminal A (P = .39) or luminal B/HER2-positive (P = .45) breast cancer. pCR in HER2-positive (nonluminal) and triple-negative tumors was associated with excellent prognosis. pCR defined as no invasive and no in situ residuals in breast and nodes can best discriminate between patients with favorable and unfavorable outcomes. Patients with noninvasive or focal-invasive residues or involved lymph nodes should not be considered as having achieved pCR. pCR is a suitable surrogate end point for patients with luminal B/HER2-negative, HER2-positive (nonluminal), and triple-negative disease but not for those with luminal B/HER2-positive or luminal A tumors.

Renal medullary carcinoma: molecular, pathological and clinical evidence for treatment with topoisomerase-inhibiting therapy.

PubMed

Schaeffer, Edward M; Guzzo, Thomas J; Furge, Kyle A; Netto, George; Westphal, Michael; Dykema, Karl; Yang, Ximing; Zhou, Ming; Teh, Bin Tean; Pavlovich, Christian P

2010-07-01

Aetiology (case series) Level of Evidence 4. To present the molecular rationale and potential clinical benefit of topoisomerase II (TopoII)-inhibiting therapy for renal medullary carcinoma (RMC), a rare but extremely lethal form of kidney cancer that classically afflicts young men with sickle-cell trait. The current therapeutic approach with these aggressive tumours is radical nephrectomy followed by systemic chemotherapy, but the prognosis remains dismal. The whole-genome expression was analysed in four RMC tumours. We also report a case of metastatic RMC in which a complete response was achieved for 9 months using a TopoII-inhibiting therapy. Expanded whole-genome expression analysis showed increases of TopoII in all cases. There was also overall deregulation of DNA remodelling and repair, and an ontological association between RMC and urothelial carcinoma. Using a TopoII-inhibiting agent, there was a complete response for 9 months in a patient with metastatic RMC. This report provides molecular evidence for the rational use of TopoII inhibitors in the treatment of RMC.

Non-Hodgkin's lymphomas of the tonsil: a retrospective analysis of twenty-eight patients with primary tonsillary lymphoma.

PubMed

Barişta, I; Tekuzman, G; Güllü, I; Baltali, E; Kars, A; Ozişik, Y; Güler, N; Celik, I; Atahan, I L; Firat, D

1995-01-01

To analyze the clinical and therapeutic aspects of patients with primary tonsillary non-Hodgkin's lymphoma. Twenty-eight patients with primary tonsillary non-Hodgkin's lymphoma who had been followed in the Hacettepe Oncology Institute between 1974 and 1992 were retrospectively analyzed. Fifteen patients were male, 13 were female. Median age was 55 years. Constitutional symptoms were present in 10 patients (35.7%). Stages according to the Ann Arbor classification were I and II in 12 and 16 patients, respectively. According to the Rappaport classification, poorly differentiated lymphocytic was the most common pathologic subgroup (42.9%). Grades according to the Working Formulation were low, intermediate and high in 3, 22 and 3 patients, respectively. Twenty-two patients had received chemotherapy. Cyclophosphamide, vincristine and prednisone (CVP), and cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) were the regimens most commonly employed. Eighteen patients received radiotherapy to Waldeyer's ring and neck. Eight patients achieved remission with chemotherapy plus radio-therapy, 7 patients with chemotherapy alone, and 5 patients with radiotherapy alone. In addition to the 20 patients who achieved complete remission, 3 patients achieved partial remission; the overall response rate was 82.1%. The response rates and survival attained with the combined modality, chemotherapy, or radiotherapy alone were not statistically different (P > 0.05). The median follow-up was 14 months. Overall and disease-free survival at 5 years were 62.6% and 77.6%, respectively. Pathologic grade was the most important prognostic factor influencing overall survival in the Cox multivariate model. Poorly differentiated lymphocytic lymphomas were the most common pathologic subtype, and pathologic grade was the most important prognostic factor to influence survival in the present study. Although combined modality treatment did not appear to be superior to chemotherapy or radiotherapy alone, a larger number of patients is needed to draw definite conclusions.

Impaired Decisional Impulsivity in Pathological Videogamers

PubMed Central

Irvine, Michael A.; Worbe, Yulia; Bolton, Sorcha; Harrison, Neil A.; Bullmore, Edward T.; Voon, Valerie

2013-01-01

Background Pathological gaming is an emerging and poorly understood problem. Impulsivity is commonly impaired in disorders of behavioural and substance addiction, hence we sought to systematically investigate the different subtypes of decisional and motor impulsivity in a well-defined pathological gaming cohort. Methods Fifty-two pathological gaming subjects and age-, gender- and IQ-matched healthy volunteers were tested on decisional impulsivity (Information Sampling Task testing reflection impulsivity and delay discounting questionnaire testing impulsive choice), and motor impulsivity (Stop Signal Task testing motor response inhibition, and the premature responding task). We used stringent diagnostic criteria highlighting functional impairment. Results In the Information Sampling Task, pathological gaming participants sampled less evidence prior to making a decision and scored fewer points compared with healthy volunteers. Gaming severity was also negatively correlated with evidence gathered and positively correlated with sampling error and points acquired. In the delay discounting task, pathological gamers made more impulsive choices, preferring smaller immediate over larger delayed rewards. Pathological gamers made more premature responses related to comorbid nicotine use. Greater number of hours played also correlated with a Motivational Index. Greater frequency of role playing games was associated with impaired motor response inhibition and strategy games with faster Go reaction time. Conclusions We show that pathological gaming is associated with impaired decisional impulsivity with negative consequences in task performance. Decisional impulsivity may be a potential target in therapeutic management. PMID:24146789

Host regulation of liver fibroproliferative pathology during experimental schistosomiasis via interleukin-4 receptor alpha.

PubMed

Nono, Justin Komguep; Ndlovu, Hlumani; Aziz, Nada Abdel; Mpotje, Thabo; Hlaka, Lerato; Brombacher, Frank

2017-08-01

Interleukin-4 receptor (IL-4Rα) is critical for the initiation of type-2 immune responses and implicated in the pathogenesis of experimental schistosomiasis. IL-4Rα mediated type-2 responses are critical for the control of pathology during acute schistosomiasis. However, type-2 responses tightly associate with fibrogranulomatous inflammation that drives host pathology during chronic schistosomiasis. To address such controversy on the role of IL-4Rα, we generated a novel inducible IL-4Rα-deficient mouse model that allows for temporal knockdown of il-4rα gene after oral administration of Tamoxifen. Interrupting IL-4Rα mediated signaling during the acute phase impaired the development of protective type-2 immune responses, leading to rapid weight loss and premature death, confirming a protective role of IL-4Rα during acute schistosomiasis. Conversely, IL-4Rα removal at the chronic phase of schistosomiasis ameliorated the pathological fibro-granulomatous pathology and reversed liver scarification without affecting the host fitness. This amelioration of the morbidity was accompanied by a reduced Th2 response and increased frequencies of FoxP3+ Tregs and CD1dhiCD5+ Bregs. Collectively, these data demonstrate that IL-4Rα mediated signaling has two opposing functions during experimental schistosomiasis depending on the stage of advancement of the disease and indicate that interrupting IL-4Rα mediated signaling is a viable therapeutic strategy to ameliorate liver fibroproliferative pathology in diseases like chronic schistosomiasis.

Quantifying the Benefit of a Pathologic Complete Response After Neoadjuvant Chemoradiotherapy in the Treatment of Esophageal Cancer

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

Scheer, Richard V.; Fakiris, Achilles J.; Johnstone, Peter A.S., E-mail: pajohnst@iupui.edu

Purpose: To better define the benefit of a pathologic complete response (pCR) after neoadjuvant chemoradiotherapy in the treatment of esophageal and gastroesophageal cancer, we undertook a comprehensive review of the literature to derive a pooled analysis of crude survival data and quantify the survival benefit of pCR vs. residual disease at esophagectomy. Methods and Materials: In all, 22 articles were reviewed. Crude overall survival data, stratified by patients with pCR vs. those with residual disease at esophagectomy, were collected and analyzed using a chi-square analysis. The relative and absolute survival benefit of achieving a pCR were calculated and analyzed. Finally,more » stratified median survival times were also analyzed. Results: Overall survival for patients with pCR was 93.1%, 75.0%, and 50.0% at 2, 3, and 5 years, respectively, whereas it was 36.8%, 29.0%, and 22.6% for patients with residual tumor (p < 0.025). The mean relative survival benefit of pCR at 2, 3, and 5 years was 2.05, 2.35, and 2.84, respectively. The mean absolute survival benefit of pCR was 35.66%, 33.79%, and 33.20%, respectively. Median survival times for patients with pCR were significantly longer than for those with residual tumor (p = 0.011). Conclusion: In esophageal and gastroesophageal cancers, pCR seems to significantly increase overall survival in patients undergoing neoadjuvant chemoradiotherapy. Specifically, the data suggest that patients with pCR are two to three times more likely to survive than are those with residual tumor at esophagectomy. Moreover, these data suggest that 33-36% more patients survive when pCR is achieved than when it is not.« less

Pathological complete response in breast cancer patients receiving anthracycline and taxane-based neoadjuvant chemotherapy: Evaluating the effect of race/ethnicity

PubMed Central

Chavez-MacGregor, Mariana; Litton, Jennifer; Chen, Huiqin; Giordano, Sharon H.; Hudis, Clifford A.; Wolff, Antonio C.; Valero, Vicente; Hortobagyi, Gabriel N.; Bondy, Melissa L.; Gonzalez-Angulo, Ana Maria

2010-01-01

Purpose To evaluate the influence of race/ethnicity and tumor subtype in pathological complete response (pCR) following treatment with neoadjuvant chemotherapy. Methods 2074 patients diagnosed with breast cancer between 1994 and 2008, treated with neoadjuvant anthracycline- and taxane-based chemotherapy, were included. pCR was defined as no residual invasive cancer in the breast and axilla. Kaplan-Meier product-limit was used to calculate survival outcomes. Cox proportional hazards models were fitted to determine the relationship of patient and tumor variables with outcome. Results Median age was 50 years, 14.6% patients were black, 15.2% Hispanic, 64.3% White, and 5.9% other race. There were no differences in pCR rates among race/ethnicity: (12.3% in black, 14.2% in Hispanics, 12.3% in whites and 11.5% in others, p=.788). Lack of pCR, breast cancer subtype, grade 3 tumors, and lymphovascular invasion were associated with worse RFS and OS (p≤.0001). Differences in RFS by race/ethnicity were seen in the patients with hormone receptor-positive disease, p=.007. In multivariate analysis, Hispanics had improved RFS (HR, 95% CI 0.69; 0.49-0.97) and OS (HR, 95% CI 0.63; 0.41-0.97); blacks had a trend to worse outcomes (RFS:HR, 95% CI 1.28; 0.97-1.68, OS:HR, 1.32; 95% CI; 0.97-1.81) when compared to whites. Conclusions In this cohort of patients, race/ethnicity was not significantly associated with pCR rates. In a multivariate analysis we observed improved outcomes in Hispanics and a trend towards worse outcomes in black patients, when compared to whites. Further research is needed to explore the potential differences in biology and outcomes. PMID:20564153

Quantifying the benefit of a pathologic complete response after neoadjuvant chemoradiotherapy in the treatment of esophageal cancer.

PubMed

Scheer, Richard V; Fakiris, Achilles J; Johnstone, Peter A S

2011-07-15

To better define the benefit of a pathologic complete response (pCR) after neoadjuvant chemoradiotherapy in the treatment of esophageal and gastroesophageal cancer, we undertook a comprehensive review of the literature to derive a pooled analysis of crude survival data and quantify the survival benefit of pCR vs. residual disease at esophagectomy. In all, 22 articles were reviewed. Crude overall survival data, stratified by patients with pCR vs. those with residual disease at esophagectomy, were collected and analyzed using a chi-square analysis. The relative and absolute survival benefit of achieving a pCR were calculated and analyzed. Finally, stratified median survival times were also analyzed. Overall survival for patients with pCR was 93.1%, 75.0%, and 50.0% at 2, 3, and 5 years, respectively, whereas it was 36.8%, 29.0%, and 22.6% for patients with residual tumor (p < 0.025). The mean relative survival benefit of pCR at 2, 3, and 5 years was 2.05, 2.35, and 2.84, respectively. The mean absolute survival benefit of pCR was 35.66%, 33.79%, and 33.20%, respectively. Median survival times for patients with pCR were significantly longer than for those with residual tumor (p = 0.011). In esophageal and gastroesophageal cancers, pCR seems to significantly increase overall survival in patients undergoing neoadjuvant chemoradiotherapy. Specifically, the data suggest that patients with pCR are two to three times more likely to survive than are those with residual tumor at esophagectomy. Moreover, these data suggest that 33-36% more patients survive when pCR is achieved than when it is not. Copyright © 2011 Elsevier Inc. All rights reserved.

Phase II Trial of Full-Dose Gemcitabine and Bevacizumab in Combination With Attenuated Three-Dimensional Conformal Radiotherapy in Patients With Localized Pancreatic Cancer

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

Small, William, E-mail: wsmall@nmff.or; Mulcahy, Mary F.; Rademaker, Alfred

Purpose: To evaluate response rate, survival, and toxicity in patients with nonmetastatic pancreatic cancer treated with gemcitabine, bevacizumab, and radiotherapy. Methods and Materials: Patients received three cycles of therapy over 10 weeks. In total, treatment consisted of intravenous (IV) gemcitabine, 1,000 mg/m{sup 2}, every 1 to 2 weeks (7 doses), IV bevacizumab, 10 mg/kg every 2 weeks (5 doses), and 36 Gy of radiotherapy (2.4-Gy fractions during cycle two). Response was assessed by cross-sectional imaging and carbohydrate antigen 19-9 (CA 19-9) levels. Patients with resectable tumors underwent surgery 6 to 8 weeks after the last dose of bevacizumab. Maintenance gemcitabinemore » and bevacizumab doses were delivered to patients who had unresected tumors and no progression. Results: Twenty-eight of the 32 enrolled patients completed all three cycles. The median follow-up was 11.07 months. Most grade 3 or 4 toxicities occurred in the initial treatment phase; the most frequent toxicities were leukopenia (21%), neutropenia (17%), and nausea (17%). At week 10, 1 patient (4%) had a complete response, 2 patients (7%) had partial responses, 21 patients (75%) had stable disease, and 4 patients (14%) had progressive disease. The median pretreatment and posttreatment CA 19-9 levels (25 patients) were 184.3 and 57.9 U/ml, respectively (p = 0.0006). One of 10 patients proceeding to surgery experienced a major complication. Two of 6 patients undergoing resection had complete pathologic responses. The median progression-free and overall survival durations were 9.9 months and 11.8 months, respectively. Conclusions: The combination of full-dose gemcitabine, bevacizumab, and radiotherapy was active and was not associated with a high rate of major surgical complications.« less

Biomaterials, fibrosis, and the use of drug delivery systems in future antifibrotic strategies.

PubMed

Love, Ryan J; Jones, Kim S

2009-01-01

All biomaterials, when implanted into the body, elicit an inflammatory response that evolves into fibrovascular tissue formation on and around the material. As a result, material scientists and tissue engineers should be concerned about host response to tissue-engineered constructs that have a biomaterial component, because the host response to this component will interfere with device function and reduce the lifespan of tissue engineering devices in vivo. The fibrotic response to biomaterials is not unlike pathological fibrosis of the liver, lung, kidney, and peritoneum in many ways: i) the presence of mononuclear leukocytes are common in the local environment of both pathological fibrosis and biomaterial-induced fibrosis even though cells of mesenchymal origin are responsible for laying the majority of the extracellular matrix; ii) paracrine-signaling molecules, such as transforming growth factor beta;1, are essential mediators of fibrosis, whether it is pathological or biomaterial induced; and iii) injury and/or the presence of foreign materials (including bacterial components, toxins, or man-made objects) are essential initiators for the development of the fibrotic response. This review discusses mechanisms and research methodology related to pathological fibrosis that is of interest to researchers focused on biomaterials. Potential research models for the study of fibrosis from the fields of biomaterials and drug delivery are also discussed, which may be of interest to scientists working on the pathology of fibrotic disease.

Evaluation of the fate and pathological response in the lung and pleura of brake dust alone and in combination with added chrysotile compared to crocidolite asbestos following short-term inhalation exposure

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

Bernstein, D.M., E-mail: davidb@itox.ch; Rogers, R.A., E-mail: rarogers5@yahoo.com; Sepulveda, R.

This study was designed to provide an understanding of the biokinetics and potential toxicology in the lung and pleura following inhalation of brake dust following short term exposure in rats. The deposition, translocation and pathological response of brake-dust derived from brake pads manufactured with chrysotile were evaluated in comparison to the amphibole, crocidolite asbestos. Rats were exposed by inhalation 6 h/day for 5 days to either brake-dust obtained by sanding of brake-drums manufactured with chrysotile, a mixture of chrysotile and the brake-dust or crocidolite asbestos. The chrysotile fibers were relatively biosoluble whereas the crocidolite asbestos fibers persisted through the life-timemore » of the animal. This was reflected in the lung and the pleura where no significant pathological response was observed at any time point in the brake dust or chrysotile/brake dust exposure groups through 365 days post exposure. In contrast, crocidolite asbestos produced a rapid inflammatory response in the lung parenchyma and the pleura, inducing a significant increase in fibrotic response in both of these compartments. Crocidolite fibers were observed embedded in the diaphragm with activated mesothelial cells immediately after cessation of exposure. While no chrysotile fibers were found in the mediastinal lymph nodes, crocidolite fibers of up to 35 μm were observed. These results provide support that brake-dust derived from chrysotile containing brake drums would not initiate a pathological response in the lung or the pleural cavity following short term inhalation. - Highlights: • Evaluated brake dust w/wo added chrysotile in comparison to crocidolite asbestos. • Persistence, translocation, pathological response in the lung and pleural cavity. • Chrysotile cleared rapidly from the lung while the crocidolite asbestos persisted. • No significant pathology in lung or pleural cavity observed at any time point in the brake-dust groups. • Crocidolite quickly produced pathological response in the lung and pleural cavity.« less

College Students' Gambling Behavior: When Does It Become Harmful?

ERIC Educational Resources Information Center

Weinstock, Jeremiah; Whelan, James P.; Meyers, Andrew

2008-01-01

Objective: The authors investigated behavioral indicators of pathological gambling in a college student sample. Participants and Methods: The authors administered a diagnostic interview for pathological gambling to 159 college students, who also completed a demographic questionnaire, and a self-report measure of psychological distress. Results:…

76 FR 19776 - Agency Information Collection Activities: Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-08

... Program to Provide Outpatient Physical Therapy and/or Speech Pathology Services, and (CMS-1893) Outpatient Physical Therapy--Speech Pathology Survey Report; Use: CMS-1856 is used as an application to be completed by providers of outpatient physical therapy and/or speech- [[Page 19777

Clinicopathological outcomes of preoperative chemoradiotherapy using S-1 plus Irinotecan for T4 lower rectal cancer.

PubMed

Beppu, Naohito; Yoshie, Hidenori; Kimura, Fumihiko; Aihara, Tsukasa; Doi, Hiroshi; Kamikonya, Norihiko; Matsubara, Nagahide; Tomita, Naohiro; Yanagi, Hidenori; Yamanaka, Naoki

2016-07-01

To investigate the clinicopathological outcomes of patients with T4 lower rectal cancer treated using preoperative chemoradiotherapy with S-1 plus Irinotecan. Between 2005 and 2011, 35 patients with T4M0 lower rectal cancer, diagnosed initially as T4a in 12 and as T4b in 23, were treated with 45 Gy of radiotherapy concomitantly with S-1 plus Irinotecan. The median follow-up period was 50.6 months (range 2-123 months). A total of 32 patients (91.4 %) completed the radiotherapy and 26 (74.3 %) completed the full chemotherapy regimen. Radical surgery was then performed in 33 (94.3 %) of the 35 patients after the exclusion of two patients, who had macroscopic residual disease. The pathological diagnosis was downstaged from T4a to ypT0-3 in all 12 of those patients (100 %) and from T4b to ypT0-4a in 20 of those 23 patients (87.0 %). The tumor regression grade of 1a/1b/2/3 (complete response) was 10/8/15/2, respectively. In terms of long-term survival, the 5-year local relapse-free survival rate was 74.8 % and the recurrence-free survival rate was 52.0 %. This regimen may result in favorable downstaging. Moreover, in this series, pathological evidence of involvement of adjacent organs was rare following preoperative chemoradiotherapy, in the patients with disease diagnosed as T4b at the initial staging.

Quantification of the pathological response and fate in the lung and pleura of chrysotile in combination with fine particles compared to amosite-asbestos following short-term inhalation exposure

PubMed Central

Bernstein, DM; Rogers, RA; Sepulveda, R; Donaldson, K; Schuler, D; Gaering, S; Kunzendorf, P; Chevalier, J; Holm, SE

2011-01-01

The marked difference in biopersistence and pathological response between chrysotile and amphibole asbestos has been well documented. This study is unique in that it has examined a commercial chrysotile product that was used as a joint compound. The pathological response was quantified in the lung and translocation of fibers to and pathological response in the pleural cavity determined. This paper presents the final results from the study. Rats were exposed by inhalation 6 h/day for 5 days to a well-defined fiber aerosol. Subgroups were examined through 1 year. The translocation to and pathological response in the pleura was examined by scanning electron microscopy and confocal microscopy (CM) using noninvasive methods.The number and size of fibers was quantified using transmission electron microscopy and CM. This is the first study to use such techniques to characterize fiber translocation to and the response of the pleural cavity. Amosite fibers were found to remain partly or fully imbedded in the interstitial space through 1 year and quickly produced granulomas (0 days) and interstitial fibrosis (28 days). Amosite fibers were observed penetrating the visceral pleural wall and were found on the parietal pleural within 7 days postexposure with a concomitant inflammatory response seen by 14 days. Pleural fibrin deposition, fibrosis, and adhesions were observed, similar to that reported in humans in response to amphibole asbestos. No cellular or inflammatory response was observed in the lung or the pleural cavity in response to the chrysotile and sanded particles (CSP) exposure. These results provide confirmation of the important differences between CSP and amphibole asbestos. PMID:21639706

Biopsy Specimens Obtained 7 Days After Starting Chemoradiotherapy (CRT) Provide Reliable Predictors of Response to CRT for Rectal Cancer

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

Suzuki, Toshiyuki; Sadahiro, Sotaro, E-mail: sadahiro@is.icc.u-tokai.ac.jp; Tanaka, Akira

2013-04-01

Purpose: Preoperative chemoradiation therapy (CRT) significantly decreases local recurrence in locally advanced rectal cancer. Various biomarkers in biopsy specimens obtained before CRT have been proposed as predictors of response. However, reliable biomarkers remain to be established. Methods and Materials: The study group comprised 101 consecutive patients with locally advanced rectal cancer who received preoperative CRT with oral uracil/tegafur (UFT) or S-1. We evaluated histologic findings on hematoxylin and eosin (H and E) staining and immunohistochemical expressions of Ki67, p53, p21, and apoptosis in biopsy specimens obtained before CRT and 7 days after starting CRT. These findings were contrasted with themore » histologic response and the degree of tumor shrinkage. Results: In biopsy specimens obtained before CRT, histologic marked regression according to the Japanese Classification of Colorectal Carcinoma (JCCC) criteria and the degree of tumor shrinkage on barium enema examination (BE) were significantly greater in patients with p21-positive tumors than in those with p21-negative tumors (P=.04 and P<.01, respectively). In biopsy specimens obtained 7 days after starting CRT, pathologic complete response, histologic marked regression according to both the tumor regression criteria and JCCC criteria, and T downstaging were significantly greater in patients with apoptosis-positive and p21-positive tumors than in those with apoptosis-negative (P<.01, P=.02, P=.01, and P<.01, respectively) or p21-negative tumors (P=.03, P<.01, P<.01, and P=.02, respectively). The degree of tumor shrinkage on both BE as well as MRI was significantly greater in patients with apoptosis-positive and with p21-positive tumors than in those with apoptosis-negative or p21-negative tumors, respectively. Histologic changes in H and E-stained biopsy specimens 7 days after starting CRT significantly correlated with pathologic complete response and marked regression on both JCCC and tumor regression criteria, as well as with tumor shrinkage on BE and MRI (P<.01, P<.01, P<.01, P<.01, and P=.03, respectively). Conclusions: Immunohistochemical expressions of p21 and apoptosis together with histologic changes on H and E-stained biopsy specimens obtained 7 days after starting CRT are strong predictors of the response to CRT.« less

Contrast-enhanced spectral mammography in neoadjuvant chemotherapy monitoring: a comparison with breast magnetic resonance imaging.

PubMed

Iotti, Valentina; Ravaioli, Sara; Vacondio, Rita; Coriani, Chiara; Caffarri, Sabrina; Sghedoni, Roberto; Nitrosi, Andrea; Ragazzi, Moira; Gasparini, Elisa; Masini, Cristina; Bisagni, Giancarlo; Falco, Giuseppe; Ferrari, Guglielmo; Braglia, Luca; Del Prato, Alberto; Malavolti, Ivana; Ginocchi, Vladimiro; Pattacini, Pierpaolo

2017-09-11

Neoadjuvant-chemotherapy (NAC) is considered the standard treatment for locally advanced breast carcinomas. Accurate assessment of disease response is fundamental to increase the chances of successful breast-conserving surgery and to avoid local recurrence. The purpose of this study was to compare contrast-enhanced spectral mammography (CESM) and contrast-enhanced-MRI (MRI) in the evaluation of tumor response to NAC. This prospective study was approved by the institutional review board and written informed consent was obtained. Fifty-four consenting women with breast cancer and indication of NAC were consecutively enrolled between October 2012 and December 2014. Patients underwent both CESM and MRI before, during and after NAC. MRI was performed first, followed by CESM within 3 days. Response to therapy was evaluated for each patient, comparing the size of the residual lesion measured on CESM and MRI performed after NAC to the pathological response on surgical specimens (gold standard), independently of and blinded to the results of the other test. The agreement between measurements was evaluated using Lin's coefficient. The agreement between measurements using CESM and MRI was tested at each step of the study, before, during and after NAC. And last of all, the variation in the largest dimension of the tumor on CESM and MRI was assessed according to the parameters set in RECIST 1.1 criteria, focusing on pathological complete response (pCR). A total of 46 patients (85%) completed the study. CESM predicted pCR better than MRI (Lin's coefficient 0.81 and 0.59, respectively). Both methods tend to underestimate the real extent of residual tumor (mean 4.1mm in CESM, 7.5mm in MRI). The agreement between measurements using CESM and MRI was 0.96, 0.94 and 0.76 before, during and after NAC respectively. The distinction between responders and non-responders with CESM and MRI was identical for 45/46 patients. In the assessment of CR, sensitivity and specificity were 100% and 84%, respectively, for CESM, and 87% and 60% for MRI. CESM and MRI lesion size measurements were highly correlated. CESM seems at least as reliable as MRI in assessing the response to NAC, and may be an alternative if MRI is contraindicated or its availability is limited.

Impulsivity and Stress Response in Pathological Gamblers During the Trier Social Stress Test.

PubMed

Maniaci, G; Goudriaan, A E; Cannizzaro, C; van Holst, R J

2018-03-01

Gambling has been associated with increased sympathetic nervous system output and stimulation of the hypothalamic-pituitary-adrenal axis. However it is unclear how these systems are affected in pathological gambling. This study aimed to investigate the effect of the Trier Social Stress Test (TSST) on cortisol and on cardiac interbeat intervals in relation to impulsivity, in a sample of male pathological gamblers compared to healthy controls. In addition, we investigated the correlation between the TSST, duration of the disorder and impulsivity. A total of 35 pathological gamblers and 30 healthy controls, ranging from 19 to 58 years old and all male, participated in this study. Stress response was measured during and after the TSST by salivary cortisol and cardiac interbeat intervals; impulsivity was assessed with the Barratt Impulsiveness Scale (BIS-11). Exposure to the TSST produced a significant increase in salivary cortisol and interbeat intervals in both groups, without differences between groups. We found a negative correlation between baseline cortisol and duration of pathological gambling indicating that the longer the duration of the disorder the lower the baseline cortisol levels. Additionally, we found a main effect of impulsivity across groups on interbeat interval during the TSST, indicating an association between impulsivity and the intensity of the neurovegetative stress response during the TSST. Involvement of the hypothalamic-pituitary-adrenal axis in pathological gambling was confirmed together with evidence of a correlation between length of the disorder and diminished baseline cortisol levels. Impulsivity emerged as a personality trait expressed by pathological gamblers; however the neurovegetative response to the TSST, although associated with impulsivity, appeared to be independent of the presence of pathological gambling.

The Role of Personality Pathology in Depression Treatment Outcome with Psychotherapy and Pharmacotherapy

ERIC Educational Resources Information Center

Levenson, Jessica C.; Wallace, Meredith L.; Fournier, Jay C.; Rucci, Paola; Frank, Ellen

2012-01-01

Background: Depressed patients with comorbid personality pathology may fare worse in treatment for depression than those without this additional pathology, and comorbid personality pathology may be associated with superior response in one form of treatment relative to another, though recent findings have been mixed. We aimed to evaluate the effect…

Analysis of outcomes achieved with squamous cell carcinomas of the anus in a single university hospital over the last two decades: Clinical response rate, relapse and survival of 190 patients.

PubMed

Gravante, Gianpiero; Stephenson, James Andrew; Elshaer, Mohamed; Osman, Ahmed; Vasanthan, Subramaniam; Mullineux, Joseph H; Gani, Mohamed Akil Dilawar; Sharpe, David; Yeung, Justin; Norwood, Michael; Miller, Andrew; Boyle, Kirsten; Hemingway, David

2018-02-01

We reviewed our series of anal squamous cell carcinomas (ASCC) treated over the last two decades. ASCC patients undergoing treatment at the Leicester Royal Infirmary between 1998 and 2016 were selected. Age, gender, pathological tumor characteristics, treatment adopted, the overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS) at 5-year follow-up were recorded and calculated. A total of 190 ASCC were reviewed, of these 64.2% (n = 122) received primary radical chemoradiotherapy. Complete response rate was 92.6% (n = 113) and four patients with residual disease underwent a salvage APER. Twenty-eight patients experienced recurrent disease (23.0%) either systemic (n = 8), local (n = 14), or both (n = 6); six had a salvage APER. Complete follow-up data are available for 63.1% patients (77/122). Overall, the locoregional failure rate of primary chemoradiotherapy (residual + recurrent disease) was present in 29 patients (29/122; 23.8%). OS was 41.6% CSS was 69.2% and DFS 60.0% at 5 years follow-up. In our series of ASCC primary chemoradiotherapy had achieved significant initial complete response rates, however, long term-follow ups still present systemic and local recurrences. APR is able to treat 30% of the pelvic recurrences (6/20), the others are either associated with systemic disease or locally inoperable masses. © 2017 Wiley Periodicals, Inc.

Lack of shunt response in suspected idiopathic normal pressure hydrocephalus with Alzheimer disease pathology.

PubMed

Hamilton, Roy; Patel, Sunil; Lee, Edward B; Jackson, Eric M; Lopinto, Joanna; Arnold, Steven E; Clark, Christopher M; Basil, Anuj; Shaw, Leslie M; Xie, Sharon X; Grady, M Sean; Trojanowski, John Q

2010-10-01

To determine the impact of cortical Alzheimer disease pathology on shunt responsiveness in individuals treated for idiopathic normal pressure hydrocephalus (iNPH), 37 patients clinically diagnosed with iNPH participated in a prospective study in which performance on neurologic, psychometric, and gait measures before and 4 months after shunting was correlated with amyloid β plaques, neuritic plaques, and neurofibrillary tangles observed in cortical biopsies obtained during shunt insertion. No complications resulted from biopsy acquisition. Moderate to severe pathology was associated with worse baseline cognitive performance and diminished postoperative improvement on NPH symptom severity scales, gait measures, and cognitive instruments compared to patients lacking pathology.

The value of forceps biopsy and core needle biopsy in prediction of pathologic complete remission in locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy.

PubMed

Tang, Jing-Hua; An, Xin; Lin, Xi; Gao, Yuan-Hong; Liu, Guo-Chen; Kong, Ling-Heng; Pan, Zhi-Zhong; Ding, Pei-Rong

2015-10-20

Patients with pathological complete remission (pCR) after treated with neoadjuvant chemoradiotherapy (nCRT) have better long-term outcome and may receive conservative treatments in locally advanced rectal cancer (LARC). The study aimed to evaluate the value of forceps biopsy and core needle biopsy in prediction of pCR in LARC treated with nCRT. In total, 120 patients entered this study. Sixty-one consecutive patients received preoperative forceps biopsy during endoscopic examination. Ex vivo core needle biopsy was performed in resected specimens of another 43 consecutive patients. The accuracy for ex vivo core needle biopsy was significantly higher than forceps biopsy (76.7% vs. 36.1%; p < 0.001). The sensitivity for ex vivo core needle biopsy was significantly lower in good responder (TRG 3) than poor responder (TRG ≤ 2) (52.9% vs. 94.1%; p = 0.017). In vivo core needle biopsy was further performed in 16 patients with good response. Eleven patients had residual cancer cells in final resected specimens, among whom 4 (36.4%) patients were biopsy positive. In conclusion, routine forceps biopsy was of limited value in identifying pCR after nCRT. Although core needle biopsy might further identify a subset of patients with residual cancer cells, the accuracy was not substantially increased in good responders.

The value of forceps biopsy and core needle biopsy in prediction of pathologic complete remission in locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy

PubMed Central

Gao, Yuan-Hong; Liu, Guo-Chen; Kong, Ling-Heng; Pan, Zhi-Zhong; Ding, Pei-Rong

2015-01-01

Patients with pathological complete remission (pCR) after treated with neoadjuvant chemoradiotherapy (nCRT) have better long-term outcome and may receive conservative treatments in locally advanced rectal cancer (LARC). The study aimed to evaluate the value of forceps biopsy and core needle biopsy in prediction of pCR in LARC treated with nCRT. In total, 120patients entered this study. Sixty-one consecutive patients received preoperative forceps biopsy during endoscopic examination. Ex vivo core needle biopsy was performed in resected specimens of another 43 consecutive patients. The accuracy for ex vivo core needle biopsy was significantly higher than forceps biopsy (76.7% vs. 36.1%; p < 0.001). The sensitivity for ex vivo core needle biopsy was significantly lower in good responder (TRG 3) than poor responder (TRG ≤ 2) (52.9% vs. 94.1%; p = 0.017). In vivo core needle biopsy was further performed in 16 patients with good response. Eleven patients had residual cancer cells in final resected specimens, among whom 4 (36.4%) patients were biopsy positive. In conclusion, routine forceps biopsy was of limited value in identifying pCR after nCRT. Although core needle biopsy might further identify a subset of patients with residual cancer cells, the accuracy was not substantially increased in good responders. PMID:26416245

Human induced pluripotent stem cells can reach complete terminal maturation: in vivo and in vitro evidence in the erythropoietic differentiation model

PubMed Central

Kobari, Ladan; Yates, Frank; Oudrhiri, Noufissa; Francina, Alain; Kiger, Laurent; Mazurier, Christelle; Rouzbeh, Shaghayegh; El-Nemer, Wassim; Hebert, Nicolas; Giarratana, Marie-Catherine; François, Sabine; Chapel, Alain; Lapillonne, Hélène; Luton, Dominique; Bennaceur-Griscelli, Annelise; Douay, Luc

2012-01-01

Background Human induced pluripotent stem cells offer perspectives for cell therapy and research models for diseases. We applied this approach to the normal and pathological erythroid differentiation model by establishing induced pluripotent stem cells from normal and homozygous sickle cell disease donors. Design and Methods We addressed the question as to whether these cells can reach complete erythroid terminal maturation notably with a complete switch from fetal to adult hemoglobin. Sickle cell disease induced pluripotent stem cells were differentiated in vitro into red blood cells and characterized for their terminal maturation in terms of hemoglobin content, oxygen transport capacity, deformability, sickling and adherence. Nucleated erythroblast populations generated from normal and pathological induced pluripotent stem cells were then injected into non-obese diabetic severe combined immunodeficiency mice to follow the in vivo hemoglobin maturation. Results We observed that in vitro erythroid differentiation results in predominance of fetal hemoglobin which rescues the functionality of red blood cells in the pathological model of sickle cell disease. We observed, in vivo, the switch from fetal to adult hemoglobin after infusion of nucleated erythroid precursors derived from either normal or pathological induced pluripotent stem cells into mice. Conclusions These results demonstrate that human induced pluripotent stem cells: i) can achieve complete terminal erythroid maturation, in vitro in terms of nucleus expulsion and in vivo in terms of hemoglobin maturation; and ii) open the way to generation of functionally corrected red blood cells from sickle cell disease induced pluripotent stem cells, without any genetic modification or drug treatment. PMID:22733021

Evaluation with 3.0-T MR imaging: predicting the pathological response of triple-negative breast cancer treated with anthracycline and taxane neoadjuvant chemotherapy.

PubMed

Kim, Min Jung; Kim, Eun-Kyung; Park, Seho; Moon, Hee Jung; Kim, Seung Il; Park, Byeong-Woo

2015-09-01

Triple-negative breast cancer (TNBC) which expresses neither hormonal receptors nor HER-2 is associated with poor prognosis and shorter survival. Several studies have suggested that TNBC patients attaining pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) show a longer survival than those without pCR. To assess the accuracy of 3.0-T breast magnetic resonance imaging (MRI) in predicting pCR and to evaluate the clinicoradiologic factors affecting the diagnostic accuracy of 3.0-T breast MRI in TNBC patients treated with anthracycline and taxane (ACD). This retrospective study was approved by the institutional review board; patient consent was not required. Between 2009 and 2012, 35 TNBC patients with 3.0-T breast MRI prior to (n = 26) or after (n = 35) NAC were included. MRI findings were reviewed according to pCR to chemotherapy. The diagnostic accuracy of 3.0-T breast MRI for predicting pCR and the clinicoradiological factors affecting MRI accuracy and response to NAC were analyzed. 3.0-T MRI following NAC with ACD accurately predicted pCR in 91.4% of TNBC patients. The residual tumor size between pathology and 3.0-T MRI in non-pCR cases showed a higher correlation in the Ki-67-positive TNBC group (r = 0.947) than in the Ki-67 negative group (r = 0.375) with statistical trends (P = 0.069). Pre-treatment MRI in the non-pCR group compared to the pCR group showed a larger tumor size (P = 0.030) and non-mass presentation (P = 0.015). 3.0-T MRI in TNBC patients following NAC with ACD showed a high accuracy for predicting pCR to NAC. Ki-67 can affect the diagnostic accuracy of 3.0-T MRI for pCR to NAC with ACD in TNBC patients. © The Foundation Acta Radiologica 2014.

Predictive value of PET-CT for pathological response in stages II and III breast cancer patients following neoadjuvant chemotherapy with docetaxel.

PubMed

García García-Esquinas, Marta A; Arrazola García, Juan; García-Sáenz, José A; Furió-Bacete, V; Fuentes Ferrer, Manuel E; Ortega Candil, Aída; Cabrera Martín, María N; Carreras Delgado, José L

2014-01-01

To prospectively study the value of PET-CT with fluorine-18 fluorodeoxyglucose (FDG) to predict neoadjuvant chemotherapy (NAC) response of locoregional disease of stages II and III breast cancer patients. A written informed consent and approval were obtained from the Ethics Committee. PET-CT accuracy in the prediction of pathologic complete response (pCR) after NAC was studied in primary tumors and lymph node metastasis in 43 women (mean age: 50 years: range: 27-71 years) with histologically proven breast cancer between December 2009 and January 2011. PET-CT was performed at baseline and after NAC. SUV(max) percentage changes (ΔSUV(max)) were compared with pathology findings at surgery. Receiver-operator characteristic (ROC) analysis was used to discriminate between locoregional pCR and non-pCR. In patients not achieving pCR, it was investigated if ΔSUV(max) could accurately identify the residual cancer burden (RCB) classes: RCB-I (minimal residual disease (MRD)), RCB-II (moderate RD), and RCB-III (extensive RD). pCR was obtained in 11 patients (25.6%). Residual disease was found in 32 patients (74.4%): 16 (37.2%) RCB-I, 15 (35.6%) RCB-II and 2 (4.7%) RCB-III. Sensitivity, specificity, and accuracy to predict pCR were 90.9%, 90.6%, and 90.7%, respectively. Specificity was 94.1% in the identification of a subset of patients who had either pCR or MRD. Accuracy of ΔSUV(max) in the locoregional disease of stages II and III breast cancer patients after NAC is high for the identification of pCR cases. Its specificity is potentially sufficient to identify a subgroup of patients who could be managed with conservative surgery. Copyright © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.

Combination chemotherapy of carboplatin and paclitaxel for advanced/metastatic salivary gland carcinoma patients: differences in responses by different pathological diagnoses.

PubMed

Nakano, Kenji; Sato, Yukiko; Sasaki, Tohru; Shimbashi, Wataru; Fukushima, Hirofumi; Yonekawa, Hiroyuki; Mitani, Hiroki; Kawabata, Kazuyoshi; Takahashi, Shunji

2016-09-01

A standard chemotherapy for recurrent/metastatic salivary gland cancers has not been established. Combination chemotherapy of carboplatin and paclitaxel should be evaluated as a treatment option. This study retrospectively reviewed salivary gland cancer patients who received combination chemotherapy of carboplatin and paclitaxel. The differences in objective responses and in the prognoses according to the different pathological diagnoses were evaluated. A total of 38 patients were enrolled in the study; of them, 18 had salivary duct carcinomas (SDCs), nine had adenoid cystic carcinomas (ACCs), and 11 had other pathological diagnoses. Objective responses were observed in 15 (39%) patients. The median progression-free survival (PFS) was 6.5 months, and the median overall survival (OS) was 26.5 months. ACC patients had relatively low response rates (9%), but there were no significant differences in PFS or OS compared to other sub-types. The treatment was well tolerated, with few adverse events. Salivary gland cancer patients showed a moderate clinical response to the combination chemotherapy of carboplatin and paclitaxel. The objective response rates differed according to the pathological diagnoses, but there were no significant differences in prognoses.

[A patient with thyroid cancer evaluated according to Response Evaluation Criteria in Solid Tumors during treatment for breast cancer recurrence in hepatic and cervical lymph nodes].

PubMed

Hayashi, Keiko; Enomoto, Takumo; Oshida, Sayuri; Habiro, Takeyoshi; Hatate, Kazuhiko; Sengoku, Norihiko; Watanabe, Masahiko

2013-11-01

We describe a case of a 69-year-old woman who underwent left breast-preserving surgery and axillary dissection for left-sided breast cancer at 60 years of age. The histopathological diagnosis was papillotubular carcinoma, luminal A (pathological T1N0M0).In the eighth year after surgery, computed tomography (CT) revealed recurrence in the liver and cervical lymph node metastasis. The patient did not respond to 3 months of treatment with letrozole (progressive disease [PD]). Six courses of chemotherapy with epirubicin and cyclophosphamide (EC) were administered. Subsequently, the attending physician was replaced while the patient was receiving paclitaxel( PTX).After 4 courses of treatment with PTX, the liver metastasis disappeared (complete response [CR]).However, the cervical lymph nodes did not shrink (PD).The cytological diagnosis was papillary thyroid cancer with associated cervical lymph node metastasis. Total thyroidectomy and D3b cervical lymph node dissection were performed. The pathological diagnosis was pEx0T1bN1Mx, pStage IVA disease. Replacement of the attending physician is a critical turning point for patients. During chemotherapy or hormone therapy for breast cancer, each organ should be evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST).In the case of our patient, thyroid cancer was diagnosed according to RECIST. Cancer specialists should bear in mind that the treatment policy may change dramatically depending on the results of RECIST assessment.

Characteristics of vestibular evoked myogenic potentials in children with enlarged vestibular aqueduct.

PubMed

Zhou, Guangwei; Gopen, Quinton

2011-01-01

To explore the characteristics of vestibular evoked myogenic potential (VEMP) in children with enlarged vestibular aqueduct (EVA) and to determine the diagnostic value of VEMP testing for this particular inner ear structural anomaly. Retrospective cohort study in a pediatric tertiary care facility. A total of 25 pediatric cases (37 ears) of EVA were identified with complete records, including otologic evaluation, CT scan of the temporal bone, and audiologic assessment. Results of audiometry, tympanometry, and VEMP testing were analyzed. Hearing loss was found in 97% (36/37) of the ears with EVA. Airbone gaps (conductive components) were found in all hearing losses with normal middle ear pressure and mobility. Abnormally low threshold VEMP responses were found in 92% (34/37) of the ears with EVA. VEMP responses were absent unilaterally in three EVA patients who had vestibular complaints. No clear correlation was found between the size of EVA and the audiologic findings. The presence of airbone gaps in children with EVA was found without apparent middle ear pathology. Characteristics of VEMP in EVA were lower thresholds and higher amplitudes despite of the presence of airbone gaps. The abnormally low threshold VEMP responses suggested a "third" window effect in the pathologic condition of EVA. Unilateral absence of VEMP may implicate peripheral vestibular impairment. The findings from our study are helpful in clinical evaluation of young children who usually give limited and ambiguous input regarding their hearing and vestibular problems.

Tumor response and negative distal resection margins of rectal cancer after hyperthermochemoradiation therapy.

PubMed

Tsutsumi, Soichi; Tabe, Yuichi; Fujii, Takaaki; Yamaguchi, Satoru; Suto, Toshinaga; Yajima, Reina; Morita, Hiroki; Kato, Toshihide; Shioya, Mariko; Saito, Jun-Ichi; Asao, Takayuki; Nakano, Takashi; Kuwano, Hiroyuki

2011-11-01

The safety of regional hyperthermia has been tested in locally advanced rectal cancer. The aim of this study was to assess the effects of shorter distal margins on local control and survival in rectal cancer patients who were treated with preoperative hyperthermochemoradiation therapy (HCRT) and underwent rectal resection by using the total mesorectal excision (TME) method. Ninety-three patients with rectal adenocarcinoma who received neoadjuvant HCRT (total radiation: 50 Gy) were included in this study. Surgery was performed 8 weeks after HCRT, and each resected specimen was evaluated histologically. Length of distal surgical margins, status of circumferential margins, pathological response, and tumor node metastasis stage were examined for their effects on recurrence and survival. Fifty-eight (62.4%) patients had tumor regression, and 20 (21.5%) had a pathological complete response. Distal margin length ranged from 1 to 55 mm (median, 21 mm) and did not correlate with local recurrence (p=0.57) or survival (p=0.75) by univariate analysis. Kaplan-Meier estimates of recurrence-free survival and local recurrence for the <10 mm versus ≥10 mm groups were not significantly different. Positive circumferential margins and failure of tumors to respond were unfavorable factors in survival. Distal resection margins that are shorter than 10 mm but are not positive appear to be equivalent to longer margins in patients who undergo HCRT followed by rectal resection with TME. To improve the down-staging rate, additional studies are needed.

Physician Scientist Research Pathway Leading to Certification by the American Board of Pathology.

PubMed

Weiss, Sharon W; Johnson, Rebecca L

2016-01-01

In 2014, the American Board of Pathology, in response to the pathology community, approved a physician scientist research pathway. This brief report summarizes the history of and objectives for creating the physician scientist research pathway and the requirements of the American Board of Pathology for the certification of physician scientist research pathway trainees.

The muscle findings in the neuroleptic malignant syndrome associated with lysergic acid diethylamide.

PubMed Central

Behan, W M; Bakheit, A M; Behan, P O; More, I A

1991-01-01

A detailed pathological description of the muscle findings in a case of the neuroleptic malignant syndrome (NMS) following ingestion of lysergic acid diethylamide (LSD) is given, including the first ultrastructural analysis. Focal necrosis, oedema, and hypercontraction of fibres with glycogen and lipid depletion, were identified, all of which had resolved completely a year later. The findings are compared with those in malignant hyperthermia. It is suggested that the results support the view that in NMS, the muscle rigidity is due to central mechanisms and, in both this disorder and malignant hyperthermia, it is responsible for the hyperpyrexia and its life-threatening complications. Images PMID:1940949

Successful Treatment of Aggressive Mature B-cell Lymphoma Mimicking Immune Thrombocytopenic Purpura.

PubMed

Ono, Koya; Onishi, Yasushi; Kobayashi, Masahiro; Ichikawa, Satoshi; Hatta, Shunsuke; Watanabe, Shotaro; Okitsu, Yoko; Fukuhara, Noriko; Ichinohasama, Ryo; Harigae, Hideo

2018-03-30

A 55-year-old woman suffered from hemorrhagic tendency. She had severe thrombocytopenia without any hematological or coagulatory abnormalities, and a bone marrow examination revealed an increased number of megakaryocytes without any abnormal cells or blasts. No lymphadenopathy or hepatosplenomegaly was observed on computed tomography. She was initially diagnosed with immune thrombocytopenic purpura (ITP). None of the treatments administered for ITP produced a response. However, abnormal cells were eventually found during the third bone marrow examination. The pathological diagnosis was mature B-cell lymphoma. Rituximab-containing chemotherapy produced a marked increase in the patient's platelet count, and her lymphoma went into complete remission.

Pathological Imitative Behavior and Response Preparation in Schizophrenia.

PubMed

Dankinas, Denisas; Melynyte, Sigita; Siurkute, Aldona; Dapsys, Kastytis

2017-08-01

Pathological imitative behavior (ehopraxia) is occasionally observed in schizophrenia patients. However, only a severe form of echopraxia can be detected with the help of a direct observation. Therefore, our goal was to study a latent form of pathological imitative behavior in this disorder, which is indicated by an increase of imitative tendencies. In our study, 14 schizophrenia patients and 15 healthy subjects were employed in two tasks: (a) in an imitative task they had to copy a hand action seen on a screen; (b) in a counter-imitative task they had to make a different movement (which involves an inhibition of prepotent imitative tendency that is impaired in case of pathological imitative behavior). Imitative tendencies were assessed by an interference score - a difference between counter-imitative and imitative response parameters. We also studied a response preparation in both groups by employing precueing probabilistic information. Our results revealed that schizophrenia patients were able to employ probabilistic information to prepare properly not only the imitative, but also the counter-imitative responses, the same as the healthy subjects did. Nevertheless, we detected increased prepotent imitative tendencies in schizophrenia patients, what indicates the latent pathological imitative behavior in case of this disorder. The obtained results suggest that in the case of schizophrenia problems with pathological imitative behavior more likely occurred in executive rather than in the preparatory stage of response. Our findings can help to detect a latent echopraxia in schizophrenia patients that cannot be revealed by direct observation. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Parameterizing the Logistic Model of Tumor Growth by DW-MRI and DCE-MRI Data to Predict Treatment Response and Changes in Breast Cancer Cellularity during Neoadjuvant Chemotherapy1

PubMed Central

Atuegwu, Nkiruka C; Arlinghaus, Lori R; Li, Xia; Chakravarthy, A Bapsi; Abramson, Vandana G; Sanders, Melinda E; Yankeelov, Thomas E

2013-01-01

Diffusion-weighted and dynamic contrast-enhanced magnetic resonance imaging (MRI) data of 28 patients were obtained pretreatment, after one cycle, and after completion of all cycles of neoadjuvant chemotherapy (NAC). For each patient at each time point, the tumor cell number was estimated using the apparent diffusion coefficient and the extravascular extracellular (ve) and plasma volume (vp) fractions. The proliferation/death rate was obtained using the number of tumor cells from the first two time points in conjunction with the logistic model of tumor growth, which was then used to predict tumor cellularity at the conclusion of NAC. The Pearson correlation coefficient between the predicted and the experimental number of tumor cells measured at the end of NAC was 0.81 (P = .0043). The proliferation rate estimated after the first cycle of therapy was able to separate patients who went on to achieve pathologic complete response from those who did not (P = .021) with a sensitivity and specificity of 82.4% and 72.7%, respectively. These data provide preliminary results indicating that incorporating readily available quantitative MRI data into a simple model of tumor growth can lead to potentially clinically relevant information for predicting an individual patient's response to NAC. PMID:23730404

The prevalence of proximal hamstring pathology on MRI in the asymptomatic population.

PubMed

Thompson, S M; Fung, S; Wood, D G

2017-01-01

Injury to the proximal hamstring complex (PHC) is becoming more frequently diagnosed. Patients attending our tertiary referral centre demonstrated 'pathological changes' in the unaffected normal contralateral PHC on MRI. The prevalence of PHC pathology, however, has not been previously documented in the literature in asymptomatic subjects. It is the hypothesis of this study that the natural history of asymptomatic pathological change on MRI in the PHC is not clear. The aim is to quantify the natural history of PHC degeneration. Two hundred and fifty-three consecutive patients with an asymptomatic PHC were reviewed retrospectively between 2009 and 2010. The PHC was assessed in multiple MRI planes by a specialist musculoskeletal consultant radiologist. Five hundred and six proximal hamstrings complexes were reviewed. Eighty-nine patients (35 %) were radiological normal both sides, median age 51 years (range 13-88). Thirty-four patients (13 %) had unilateral pathology, median age 55 years (range 25-89). Of these, 3 patients (1 %) had presence of a complete tear, median age 81 years (range 72-87). Sixteen patients (7 %) had tendinosis, median age 60 years (range 37-78). Fifteen patients (6 %) had a unilateral partial tear, median age 57 years (range 35-78). One hundred and thirty patients (52 %) had bilateral pathology, median age 65 years (range 25-89). Fifty-three patients (21 %) had the presence of bilateral tendinopathy alone, median age 56 years (range 25-89). Twenty-seven patients (11 %) had a partial tear on one side and tendinosis on the other, median age 68 years (range 38-89). Thirty-nine patients (15 %) had evidence of bilateral partial tears, median age 63 years (range 36-89), with 52 % demonstrating a torn conjoined and semi-membranosus tendon. The remaining 48 % had either an isolated tear of the conjoined or the semi-membranosus (the more commonly injured tendon 74 % of the time). Four patients (2 %) had bilateral complete ruptures with a median age of 68 years (range 59-78). Six patients (2 %) had a complete tear on one side and a partial tear on the other, median age 68 years (range 34-83). One patient had a complete tear on one side and tendinosis on the other, age 81 years. There is a higher prevalence of pathology in the asymptomatic population, 15 % have bilateral partial tears, and 2 % have bilateral complete tears. The semi-membranosus being the most affected, this may help clinically stratify the need for surgical intervention. I.

Predictive and Prognostic Molecular Biomarkers for Response to Neoadjuvant Chemoradiation in Rectal Cancer.

PubMed

Dayde, Delphine; Tanaka, Ichidai; Jain, Rekha; Tai, Mei Chee; Taguchi, Ayumu

2017-03-07

The standard of care in locally advanced rectal cancer is neoadjuvant chemoradiation (nCRT) followed by radical surgery. Response to nCRT varies among patients and pathological complete response is associated with better outcome. However, there is a lack of effective methods to select rectal cancer patients who would or would not have a benefit from nCRT. The utility of clinicopathological and radiological features are limited due to lack of adequate sensitivity and specificity. Molecular biomarkers have the potential to predict response to nCRT at an early time point, but none have currently reached the clinic. Integration of diverse types of biomarkers including clinicopathological and imaging features, identification of mechanistic link to tumor biology, and rigorous validation using samples which represent disease heterogeneity, will allow to develop a sensitive and cost-effective molecular biomarker panel for precision medicine in rectal cancer. Here, we aim to review the recent advance in tissue- and blood-based molecular biomarker research and illustrate their potential in predicting nCRT response in rectal cancer.

Hemoglobin level and XRCC1 polymorphisms to select patients with locally advanced rectal cancer candidate for neoadjuvant chemoradiotherapy with concurrent capecitabine and a platinum salt.

PubMed

Formica, Vincenzo; Benassi, Michaela; Del Vecchio Blanco, Giovanna; Doldo, Elena; Martano, Laura; Portarena, Ilaria; Nardecchia, Antonella; Lucchetti, Jessica; Morelli, Cristina; Giudice, Emilia; Rossi, Piero; Anselmo, Alessandro; Sileri, Pierpaolo; Sica, Giuseppe; Orlandi, Augusto; Santoni, Riccardo; Roselli, Mario

2018-05-02

A platinum salt (oxaliplatin or cisplatin) is widely used to enhance chemoradation (CRT) response. The potential of cisplatin in neoadjuvant CRT for locally advanced rectal cancer (LARC) has not been fully investigated. Consecutive patients with histologically confirmed LARC were treated with standard pelvic radiotherapy and concurrent cisplatin plus capecitabine (CisCape CRT). Surgery and eight cycles of adjuvant FOLFOX4 were offered to all patients after CRT. Common biochemical variables and key germline genetic polymorphisms were analyzed as predictors of pathological complete response (pCR). Fifty-one patients were enrolled. pCR (regression AJCC grade 0) was documented in 7 patients (14%), nearly complete response (AJCC grade 1) in 10 pts. There was a strong association between disease-free survival and AJCC grade (p 0.0047). Grade 3-4 toxicities (mainly diarrhea) was observed in 41% of patients. Among all analyzed variables, baseline hemoglobin (Hb) was significantly associated with AJCC grade 0-1 response (p 0.027). As for the pharmacogenetic analysis, XRCC1 rs25487 polymorphism was significantly associated with AJCC grade 0-1, Odds Ratio 25.8, p 0.049. AJCC grade 0-1 response rate for patients with high Hb and/or XRCC1 rs25487 G/G genotype was as high as 57%. Baseline Hb and XRCC1 polymorphisms are valuable selection criteria for the CisCape CRT regimen, given its otherwise meaningful toxicity.

TRPC6 fulfills a calcineurin signaling circuit during pathologic cardiac remodeling

PubMed Central

Kuwahara, Koichiro; Wang, Yanggan; McAnally, John; Richardson, James A.; Bassel-Duby, Rhonda; Hill, Joseph A.; Olson, Eric N.

2006-01-01

The heart responds to injury and chronic pressure overload by pathologic growth and remodeling, which frequently result in heart failure and sudden death. Calcium-dependent signaling pathways promote cardiac growth and associated changes in gene expression in response to stress. The calcium/calmodulin-dependent phosphatase calcineurin, which signals to nuclear factor of activated T cells (NFAT) transcription factors, serves as a transducer of calcium signals and is sufficient and necessary for pathologic cardiac hypertrophy and remodeling. Transient receptor potential (TRP) proteins regulate cation entry into cells in response to a variety of signals, and in skeletal muscle, expression of TRP cation channel, subfamily C, member 3 (TRPC3) is increased in response to neurostimulation and calcineurin signaling. Here we show that TRPC6 was upregulated in mouse hearts in response to activated calcineurin and pressure overload, as well as in failing human hearts. Two conserved NFAT consensus sites in the promoter of the TRPC6 gene conferred responsiveness to cardiac stress. Cardiac-specific overexpression of TRPC6 in transgenic mice resulted in heightened sensitivity to stress, a propensity for lethal cardiac growth and heart failure, and an increase in NFAT-dependent expression of β–myosin heavy chain, a sensitive marker for pathologic hypertrophy. These findings implicate TRPC6 as a positive regulator of calcineurin-NFAT signaling and a key component of a calcium-dependent regulatory loop that drives pathologic cardiac remodeling. PMID:17099778

Maximizing protection from use of oral cholera vaccines in developing country settings

PubMed Central

Desai, Sachin N; Cravioto, Alejandro; Sur, Dipika; Kanungo, Suman

2014-01-01

When oral vaccines are administered to children in lower- and middle-income countries, they do not induce the same immune responses as they do in developed countries. Although not completely understood, reasons for this finding include maternal antibody interference, mucosal pathology secondary to infection, malnutrition, enteropathy, and previous exposure to the organism (or related organisms). Young children experience a high burden of cholera infection, which can lead to severe acute dehydrating diarrhea and substantial mortality and morbidity. Oral cholera vaccines show variations in their duration of protection and efficacy between children and adults. Evaluating innate and memory immune response is necessary to understand V. cholerae immunity and to improve current cholera vaccine candidates, especially in young children. Further research on the benefits of supplementary interventions and delivery schedules may also improve immunization strategies. PMID:24861554

Neoadjuvant radiotherapy with or without chemotherapy followed by extrafascial hysterectomy for locally advanced endometrial cancer clinically extending to the cervix or parametria.

PubMed

Vargo, John A; Boisen, Michelle M; Comerci, John T; Kim, Hayeon; Houser, Christopher J; Sukumvanich, Paniti; Olawaiye, Alexander B; Kelley, Joseph L; Edwards, Robert P; Huang, Marilyn; Courtney-Brooks, Madeleine; Beriwal, Sushil

2014-11-01

For locally-advanced uterine cancer clinically extending to the cervix, two treatment paradigms exist: surgical staging radical hysterectomy with tailored adjuvant therapy or neoadjuvant therapy followed by a less extensive simple hysterectomy. Currently, insufficient data exists to guide consensus guidelines and practical application of preoperative radiotherapy. Retrospective IRB approved cohort study from 1999 to 2014 of 36 endometrial cancer patients with clinical involvement of cervix±parametria treated with neoadjuvant external beam radiotherapy (45-50.4Gy in 25-28 fractions) and image-based HDR brachytherapy (5-5.5Gy times 3-4 fractions)±chemotherapy followed by extrafascial hysterectomy performed at a median of 6weeks after radiotherapy. All patients had clinical cervical extension, 50% also had parametria extension, and 31% had nodal involvement. At the time of surgery 91% had no clinical cervical involvement, 58% had no pathologic cervical involvement, and all had margin negative resection. The pathologic complete response rate was 24%. Median follow-up from the time of surgery was 20months (range: 0-153). The 3-year local control, regional control, distant control, disease free survival and overall survival rates were 96%, 89%, 84%, 73%, and 100%. The 3-year rate of grade 3 complications was 11%, with no grade 4+ toxicity. Neoadjuvant radiation therapy±chemotherapy followed by extrafascial hysterectomy appears to be a viable option for patients with endometrial cancer clinically extending to the cervix and parametria. The HDR brachytherapy schema of 5-5.5Gy times 3-4 fractions, for a cumulative EQD2 of 60-70Gy, is well tolerated with high rates of clinical and pathological response. Copyright © 2014 Elsevier Inc. All rights reserved.

Factors that Enhance English-Speaking Speech-Language Pathologists' Transcription of Cantonese-Speaking Children's Consonants

ERIC Educational Resources Information Center

Lockart, Rebekah; McLeod, Sharynne

2013-01-01

Purpose: To investigate speech-language pathology students' ability to identify errors and transcribe typical and atypical speech in Cantonese, a nonnative language. Method: Thirty-three English-speaking speech-language pathology students completed 3 tasks in an experimental within-subjects design. Results: Task 1 (baseline) involved transcribing…

Employment Myths and Realities in Speech and Language Pathology.

ERIC Educational Resources Information Center

Chan, T. C.; Curran, Theresa; Deskin, Caroline

This study compared the professional expectations of graduate students in speech and language pathology (SLP) with the employment realities offered by the profession. A total of 89 graduate students enrolled in the SLP program at Valdosta State University (VSU) in Georgia during 1995-97 completed a seven-item questionnaire on employment prospects.…

Working Papers in Experimental Speech-Language Pathology and Audiology.

ERIC Educational Resources Information Center

Jablon, Ann, Ed.; And Others

Five papers describe clinical research completed by graduate students in speech-language pathology and audiology. The first study examines the linguistic input of three adults (a mother, teacher, and clinician) to a language impaired 8-year-old. The clinician's approach, less directive than that of the other two, facilitated spontaneous speech and…

Bone Marrow Synoptic Reporting for Hematologic Neoplasms: Guideline From the College of American Pathologists Pathology and Laboratory Quality Center.

PubMed

Sever, Cordelia; Abbott, Charles L; de Baca, Monica E; Khoury, Joseph D; Perkins, Sherrie L; Reichard, Kaaren Kemp; Taylor, Ann; Terebelo, Howard R; Colasacco, Carol; Rumble, R Bryan; Thomas, Nicole E

2016-09-01

-There is ample evidence from the solid tumor literature that synoptic reporting improves accuracy and completeness of relevant data. No evidence-based guidelines currently exist for synoptic reporting for bone marrow samples. -To develop evidence-based recommendations to standardize the basic components of a synoptic report template for bone marrow samples. -The College of American Pathologists Pathology and Laboratory Quality Center convened a panel of experts in hematopathology to develop recommendations. A systematic evidence review was conducted to address 5 key questions. Recommendations were derived from strength of evidence, open comment feedback, and expert panel consensus. -Nine guideline statements were established to provide pathology laboratories with a framework by which to develop synoptic reporting templates for bone marrow samples. The guideline calls for specific data groups in the synoptic section of the pathology report; provides a list of evidence-based parameters for key, pertinent elements; and addresses ancillary testing. -A framework for bone marrow synoptic reporting will improve completeness of the final report in a manner that is clear, succinct, and consistent among institutions.

The Impact of Residual Disease After Preoperative Systemic Therapy on Clinical Outcomes in Patients with Inflammatory Breast Cancer.

PubMed

Nakhlis, Faina; Regan, Meredith M; Warren, Laura E; Bellon, Jennifer R; Hirshfield-Bartek, Judith; Duggan, Margaret M; Dominici, Laura S; Golshan, Mehra; Jacene, Heather A; Yeh, Eren D; Mullaney, Erin E; Overmoyer, Beth

2017-09-01

Inflammatory breast cancer (IBC) is a rare and aggressive disease treated with multimodality therapy: preoperative systemic therapy (PST) followed by modified radical mastectomy (MRM), chest wall and regional nodal radiotherapy, and adjuvant biologic therapy and/or endocrine therapy when appropriate. In non-IBC, the degree of pathologic response to PST has been shown to correlate with time to recurrence (TTR) and overall survival (OS). We sought to determine if pathologic response correlates with oncologic outcomes of IBC patients. Following review of IBC patients' records (1997-2014), we identified 258 stage III IBC patients; 181 received PST followed by MRM and radiotherapy and were subsequently analyzed. Pathologic complete response (pCR) to PST, hormone receptor and human epidermal growth factor receptor 2 (HER2) status, grade, and histology were evaluated as predictors of TTR and OS by Cox model. Overall, 95/181 (52%) patients experienced recurrence; 93/95 (98%) were distant metastases (median TTR 3.2 years). Seventy-three patients (40%) died (median OS 6.9 years). pCR was associated with improved TTR (hazard ratio [HR] 0.20, 95% confidence interval [CI] 0.09-0.46, p < 0.01, univariate; HR 0.17, 95% CI 0.07-0.41, p < 0.0001, multivariate) and improved OS (HR 0.26, 95% CI 0.11-0.65, p < 0.01, univariate). In patients with pCR, grade III (HR 1.91, 95% CI 1.16-3.13, p = 0.01), and triple-negative phenotype (HR 3.54, 95% CI 1.79-6.98, p = 0.0003) were associated with shorter TTR, while residual ductal carcinoma in situ was not (HR 0.85, 95% CI 0.53-1.35, p = 0.48, multivariate). In stage III IBC, pCR was associated with prognosis, further influenced by grade, hormone receptor, and HER2 status. Investigating mechanisms that contribute to better response to PST could help improve oncologic outcomes in IBC.

Pathologic Response, When Increased by Longer Interval, Is a Marker but Not the Cause of Good Prognosis in Rectal Cancer: 17-year Follow-up of the Lyon R90-01 Randomized Trial

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

Cotte, Eddy, E-mail: eddy.cotte@chu-lyon.fr; Lyon 1 University, EMR 3738, Lyon-Sud/Charles Mérieux Medical University, Oullins; Passot, Guillaume

Purpose: The Lyon R90-01 randomized trial investigated whether the interval between preoperative radiation therapy and surgery influenced rectal cancer outcome. Long-term results are reported here after a median follow-up of 17 years. Methods and Materials: Between February 1991 and December 1995, 210 patients from 29 French centers were randomly assigned (ratio of 1:1) to groups that waited either 2 weeks (short interval [SI]) or 6 to 8 weeks (long interval [LI]) between neoadjuvant radiation therapy and surgery. The primary endpoint was sphincter-preserving surgery. Results: LI group showed a better pathologic response (complete response or few residual cells) after radiation therapy than the SImore » group (26% vs 10.3%, P=.015). A better pathologic response was associated in multivariate analysis with significant improvement of overall survival (pT: P=.0293 and pN: P=.0048) but it was irrespective of the interval duration. The median follow-up was 17.2 years. The 5-, 10-, 15-, and 17-year overall survival rates were, respectively, 66.8%, 48.7%, 40.0%, and 34.0% for the SI group and, respectively, 67.1%, 53.5%, 41.9%, and 34.0% for the LI group. There were no significant differences between groups in terms of survival (P=.7656) or local recurrence rates (SI: 14.4% vs LI: 12.1%, respectively; P=.6202). Of 24 local disease recurrences, 20 (83%) occurred during the first 2 postoperative years, and all but one (96%) occurred during the first 5 postoperative years. The rate of second new malignancies was 9.4% (19 patients). Conclusions: The radiation-induced sterilization rate of the preoperative cancer specimen was a marker of good prognosis. The interval duration (the treatment being the same) although it is modifying the sterilization rate has no impact on survival. Radiation therapy did not postpone local recurrence, because the rate of local relapse after 5 years was low. Radiation-induced cancers after radiation therapy were unusual and should not influence treatment decisions in adults.« less

Detection of residual disease after neoadjuvant chemoradiotherapy for oesophageal cancer (preSANO): a prospective multicentre, diagnostic cohort study.

PubMed

Noordman, Bo Jan; Spaander, Manon C W; Valkema, Roelf; Wijnhoven, Bas P L; van Berge Henegouwen, Mark I; Shapiro, Joël; Biermann, Katharina; van der Gaast, Ate; van Hillegersberg, Richard; Hulshof, Maarten C C M; Krishnadath, Kausilia K; Lagarde, Sjoerd M; Nieuwenhuijzen, Grard A P; Oostenbrug, Liekele E; Siersema, Peter D; Schoon, Erik J; Sosef, Meindert N; Steyerberg, Ewout W; van Lanschot, J Jan B

2018-05-31

After neoadjuvant chemoradiotherapy for oesophageal cancer, roughly half of the patients with squamous cell carcinoma and a quarter of those with adenocarcinoma have a pathological complete response of the primary tumour before surgery. Thus, the necessity of standard oesophagectomy after neoadjuvant chemoradiotherapy should be reconsidered for patients who respond sufficiently to neoadjuvant treatment. In this study, we aimed to establish the accuracy of detection of residual disease after neoadjuvant chemoradiotherapy with different diagnostic approaches, and the optimal combination of diagnostic techniques for clinical response evaluations. The preSANO trial was a prospective, multicentre, diagnostic cohort study at six centres in the Netherlands. Eligible patients were aged 18 years or older, had histologically proven, resectable, squamous cell carcinoma or adenocarcinoma of the oesophagus or oesophagogastric junction, and were eligible for potential curative therapy with neoadjuvant chemoradiotherapy (five weekly cycles of carboplatin [area under the curve 2 mg/mL per min] plus paclitaxel [50 mg/m 2 of body-surface area] combined with 41·4 Gy radiotherapy in 23 fractions) followed by oesophagectomy. 4-6 weeks after completion of neoadjuvant chemoradiotherapy, patients had oesophagogastroduodenoscopy with biopsies and endoscopic ultrasonography with measurement of maximum tumour thickness. Patients with histologically proven locoregional residual disease or no-pass during endoscopy and without distant metastases underwent immediate surgical resection. In the remaining patients a second clinical response evaluation was done (PET-CT, oesophagogastroduodenoscopy with biopsies, endoscopic ultrasonography with measurement of maximum tumour thickness, and fine-needle aspiration of suspicious lymph nodes), followed by surgery 12-14 weeks after completion of neoadjuvant chemoradiotherapy. The primary endpoint was the correlation between clinical response during clinical response evaluations and the final pathological response in resection specimens, as shown by the proportion of tumour regression grade (TRG) 3 or 4 (>10% residual carcinoma in the resection specimen) residual tumours that was missed during clinical response evaluations. This study was registered with the Netherlands Trial Register (NTR4834), and has been completed. Between July 22, 2013, and Dec 28, 2016, 219 patients were included, 207 of whom were included in the analyses. Eight of 26 TRG3 or TRG4 tumours (31% [95% CI 17-50]) were missed by endoscopy with regular biopsies and fine-needle aspiration. Four of 41 TRG3 or TRG4 tumours (10% [95% CI 4-23]) were missed with bite-on-bite biopsies and fine-needle aspiration. Endoscopic ultrasonography with maximum tumour thickness measurement missed TRG3 or TRG4 residual tumours in 11 of 39 patients (28% [95% CI 17-44]). PET-CT missed six of 41 TRG3 or TRG4 tumours (15% [95% CI 7-28]). PET-CT detected interval distant histologically proven metastases in 18 (9%) of 190 patients (one squamous cell carcinoma, 17 adenocarcinomas). After neoadjuvant chemoradiotherapy for oesophageal cancer, clinical response evaluation with endoscopic ultrasonography, bite-on-bite biopsies, and fine-needle aspiration of suspicious lymph nodes was adequate for detection of locoregional residual disease, with PET-CT for detection of interval metastases. Active surveillance with this combination of diagnostic modalities is now being assessed in a phase 3 randomised controlled trial (SANO trial; Netherlands Trial Register NTR6803). Dutch Cancer Society. Copyright © 2018 Elsevier Ltd. All rights reserved.

Exquisite Sensitivity of TP53 Mutant and Basal Breast Cancers to a Dose-Dense Epirubicin−Cyclophosphamide Regimen

PubMed Central

Espié, Marc; de Reyniès, Aurélien; Feugeas, Jean-Paul; Plassa, Louis-François; Soliman, Hany; Varna, Mariana; de Roquancourt, Anne; Lehmann-Che, Jacqueline; Beuzard, Yves; Marty, Michel; Misset, Jean-Louis; Janin, Anne; de Thé, Hugues

2007-01-01

Background In breast cancers, only a minority of patients fully benefit from the different chemotherapy regimens currently in use. Identification of markers that could predict the response to a particular regimen would thus be critically important for patient care. In cell lines or animal models, tumor protein p53 (TP53) plays a critical role in modulating the response to genotoxic drugs. TP53 is activated in response to DNA damage and triggers either apoptosis or cell-cycle arrest, which have opposite effects on cell fate. Yet, studies linking TP53 status and chemotherapy response have so far failed to unambiguously establish this paradigm in patients. Breast cancers with a TP53 mutation were repeatedly shown to have a poor outcome, but whether this reflects poor response to treatment or greater intrinsic aggressiveness of the tumor is unknown. Methods and Findings In this study we analyzed 80 noninflammatory breast cancers treated by frontline (neoadjuvant) chemotherapy. Tumor diagnoses were performed on pretreatment biopsies, and the patients then received six cycles of a dose-dense regimen of 75 mg/m2 epirubicin and 1,200 mg/m2 cyclophosphamide, given every 14 days. After completion of chemotherapy, all patients underwent mastectomies, thus allowing for a reliable assessment of chemotherapy response. The pretreatment biopsy samples were used to determine the TP53 status through a highly efficient yeast functional assay and to perform RNA profiling. All 15 complete responses occurred among the 28 TP53-mutant tumors. Furthermore, among the TP53-mutant tumors, nine out of ten of the highly aggressive basal subtypes (defined by basal cytokeratin [KRT] immunohistochemical staining) experienced complete pathological responses, and only TP53 status and basal subtype were independent predictors of a complete response. Expression analysis identified many mutant TP53-associated genes, including CDC20, TTK, CDKN2A, and the stem cell gene PROM1, but failed to identify a transcriptional profile associated with complete responses among TP53 mutant tumors. In patients with unresponsive tumors, mutant TP53 status predicted significantly shorter overall survival. The 15 patients with responsive TP53-mutant tumors, however, had a favorable outcome, suggesting that this chemotherapy regimen can overcome the poor prognosis generally associated with mutant TP53 status. Conclusions This study demonstrates that, in noninflammatory breast cancers, TP53 status is a key predictive factor for response to this dose-dense epirubicin–cyclophosphamide regimen and further suggests that the basal subtype is exquisitely sensitive to this association. Given the well-established predictive value of complete responses for long-term survival and the poor prognosis of basal and TP53-mutant tumors treated with other regimens, this chemotherapy could be particularly suited for breast cancer patients with a mutant TP53, particularly those with basal features. PMID:17388661

Confounders in interpreting pathology for safety and risk assessment

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

Wolf, Douglas C.; Mann, Peter C.

2005-02-01

The contribution of pathology to toxicity assessment is invaluable but often not clearly understood. Pathology endpoints are the central response around which human health risk assessment is frequently determined; therefore, it is important that the general toxicology community understand current concepts and nomenclature of toxicologic pathology. Toxicologic pathology encompasses the study of changes in tissue morphology that help define the risk of exposure to xenobiotics. Toxicologic pathology is a discipline that has changed and adapted over time including methods of analysis and nomenclature of lesions. As risk assessments are updated for chemicals in commerce, frequently the older literature must bemore » reviewed and reevaluated. When interpreting pathology data from animal studies, it is important to consider the biological significance of a lesion as well as its relationship to the ultimate adverse health effect. Assessing the potential for a chemical to cause harm to humans must include the examination of the entire pathology database in context of the study design, the mode of action of the chemical of concern, and using the most current interpretation of a lesion to determine the significance for human health effects of a particular tissue response.« less

Clinical outcome and prognosis of carbon ion radiotherapy on thoracic malignant tumors

NASA Astrophysics Data System (ADS)

Li, Sha

Objective To evaluate the therapeutic efficacy and side-response of high-LET carbon ion radiotherapy on thoracic malignant tumors. Methods Ten patients with pathological confirmed thoracic malignant tumors received treatment using heavy ion accelerator, which included 6 cases with non-small lung cancer, one case with small lung cancer, 2 cases with metastatic sarcomas and one case with invasive thymoma. The applied regimen included fractioned dose (5.5-6.8GyE/Fraction), one faction/day, and 7 fractions/week. The total dose ranged from 55 to 70 GyE. Results The short-term results showed that the response rate (the complete response (CR) rate +the partial response (PR) rate) was 10% at the first month, 40% at the third month and 90% at the sixth month. The overall response rate was 90% and the rate of stable disease was 10%. There was no relation between the response rate and tumor pathology (P>0.05) while significance between the response rate and the tumor volume.At median follow-up of 27 months (range, 6 to 36 months), the local control rate and free-disease rate were respectively 100% an 90% at the first year, 90% and 80% at the secondary year, 80% and 70% at the third year. The death rate due to disease progression was 20% and the non-specific death rate was 10%. Side and toxicity effects: Grade I skin effect occurred in three cases and Grade I lung effect occurred in two cases. The blood counts didn’t reach significance among pre-radiation course, peri-radiation course and post-radiation course (P>0.05). The subgoups of T cells detected in humoral immunity and cytoimmunity didn’t change between pre-radiation and post radiation(P>0.05). Conclusions Carbon ion radiotherapy is effective and safe in the management of patients with thoracic malignant tumors. There were no obvious side effects. The long term of clinical outcome and the late effect need to be further observed.

Lack of Shunt Response in Suspected Idiopathic Normal Pressure Hydrocephalus with Alzheimer Disease Pathology

PubMed Central

Hamilton, Roy; Patel, Sunil; Lee, Edward B.; Jackson, Eric M.; Lopinto, Joanna; Arnold, Steven E.; Clark, Christopher M.; Basil, Anuj; Shaw, Leslie M.; Xie, Sharon X.; Grady, M. Sean; Trojanowski, John Q.

2010-01-01

To determine the impact of cortical Alzheimer disease pathology on shunt responsiveness in individuals treated for idiopathic normal pressure hydrocephalus (iNPH), 37 patients clinically diagnosed with iNPH participated in a prospective study in which performance on neurologic, psychometric, and gait measures before and 4 months after shunting was correlated with amyloid β plaques, neuritic plaques, and neurofibrillary tangles observed in cortical biopsies obtained during shunt insertion. No complications resulted from biopsy acquisition. Moderate to severe pathology was associated with worse baseline cognitive performance and diminished postoperative improvement on NPH symptom severity scales, gait measures, and cognitive instruments compared to patients lacking pathology. PMID:20687117

[Learning pathologic anatomy during medical formation: Understanding the contribution of the motivation].

PubMed

Toquet, Claire; Normand, Adeline; Guihard, Gilles

2018-05-26

The motivations of medical students for Pathologic Anatomy are little known although they can strongly influence their academic performance. Our work focused on the analysis of the relationship between performance and motivation for Pathologic Anatomy. Second-year students (n=268) from the University of Nantes were contacted to complete a motivation questionnaire and to provide indicators of performance and attendance. The responses were analyzed in order to establish the psychometric reliability and the factorial structure of the questionnaire. The relationship between motivation and performance was explored by correlation and by linear regression studies. A cluster analysis was performed to specify the distribution of the two variables in our sample. The sample corresponded to 168 respondents with a F/M ratio similar to that of our population. Our data demonstrated the reliability of the questionnaire and a structure described by 5 motivation factors (self-determination, self-efficacy, career, grade and intrinsic motivation). The academic performance was not significantly correlated with the overall motivation or with student attendance. However, it was predicted by self-determination and self-efficacy. Our work revealed gender differences as well as the existence of two distinct clusters defined by the motivation and performance of the students. This work constitutes the first study of the motivations of French medical students for cyto-pathology. It validates a quantitative assessment tool for motivation. Finally, it explores the heterogeneity of the distribution of motivation and academic performance within a population of learners. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Human Colors-The Rainbow Garden of Pathology: What Gives Normal and Pathologic Tissues Their Color?

PubMed

Piña-Oviedo, Sergio; Ortiz-Hidalgo, Carlos; Ayala, Alberto G

2017-03-01

- Colors are important to all living organisms because they are crucial for camouflage and protection, metabolism, sexual behavior, and communication. Human organs obviously have color, but the underlying biologic processes that dictate the specific colors of organs and tissues are not completely understood. A literature search on the determinants of color in human organs yielded scant information. - To address 2 specific questions: (1) why do human organs have color, and (2) what gives normal and pathologic tissues their distinctive colors? - Endogenous colors are the result of complex biochemical reactions that produce biologic pigments: red-brown cytochromes and porphyrins (blood, liver, spleen, kidneys, striated muscle), brown-black melanins (skin, appendages, brain nuclei), dark-brown lipochromes (aging organs), and colors that result from tissue structure (tendons, aponeurosis, muscles). Yellow-orange carotenes that deposit in lipid-rich tissues are only produced by plants and are acquired from the diet. However, there is lack of information about the cause of color in other organs, such as the gray and white matter, neuroendocrine organs, and white tissues (epithelia, soft tissues). Neoplastic tissues usually retain the color of their nonneoplastic counterpart. - Most available information on the function of pigments comes from studies in plants, microorganisms, cephalopods, and vertebrates, not humans. Biologic pigments have antioxidant and cytoprotective properties and should be considered as potential future therapies for disease and cancer. We discuss the bioproducts that may be responsible for organ coloration and invite pathologists and pathology residents to look at a "routine grossing day" with a different perspective.

Difference of protein 53 expression based on radiation therapy response in cervical cancer

NASA Astrophysics Data System (ADS)

Pasaribu, H. P.; Lubis, L. I.; Dina, S.; Simanjuntak, R. Y.; Siregar, H. S.; Rivany, R.

2018-03-01

Cervical cancer is one of most common gynecological cancer in women and the leading cause of death in developing countries. An analytic study with the case-control design was conducted to determine the difference of p53 expression based on radiation therapy response in cervical cancer. The study was performed in Obstetric and Gynecology Department and Pathology Department of Adam Malik General Hospital Medan from January to February 2017. 15 paraffin blocks of acervical cancer patient with incomplete response were obtained as study samples, and 15 paraffin blocks of acervical cancer patient with complete response were obtained as control samples, The samples were collected by consecutive sampling, andan immunohistochemical assessment of p53 expression was done to assessapoptosis count and radiation response. Data were analyzed using Kruskal-Wallis with confidence interval 83.5% and p<0.05 was considered statistically significant. The study found that an increase of p53 expressionin samples with abundant apoptosis (≥5 apoptosis cells/5 HPF), p=0.033, and in incomplete response group, p=0.046. It means that p53 expression before radiation therapy can be used as an early marker for radiation therapy response in cervical cancer.

[Prevalence of pathological gambling in Lebanese students].

PubMed

Etel, C; Tabchi, S; Bou Khalil, R; Hlais, S; Richa, S

2013-02-01

Pathological gambling is a behavioral dependency on hazard games that is classified, in the DSM-IV, among impulse control disorders. According to many studies, the international prevalence of pathological ranges between 2 and 6%. This disorder is often accompanied by a considerable impact on patients' life as well as on the life of people surrounding them. Adolescents and young adults are considered to be a population at risk to develop this kind of behavioral dependency. The problem of pathological gambling is one of the major problems from which the Lebanese population of university students in Lebanese society suffers. The prevalence of pathological gambling in the Lebanese population of university students is lacking from the contemporary medical literature. In our study, five of the biggest private universities in Lebanon (Notre-Dame University of Louaizé [NDU], Lebanese American University [LAU], American University of Beirut [AUB], Saint-Joseph University [USJ] and Holy Spirit University of Kaslik [USEK]) were surveyed. Each questionnaire was based essentially on the South Oaks Gambling Screen (SOGS). Four hundred and seventy-seven questionnaires were completed in these universities. Among the 477 students that completed the questionnaire, 5.87% appeared to be suffering from pathological gambling; 25.15% of responding students presented some problems related to gambling while the rest of them, corresponding to 68.92%, had no problems related to gambling. This is the first study of its kind conducted in the Lebanon. Its interest lies in that it offers an important evaluation of the prevalence of pathological gambling in the Lebanese population of university students. According to this study, the prevalence of pathological gambling in Lebanese university students is high. Prevention programs and sensitization strategies are needed in order to prevent the occurrence of this disorder in the Lebanese young. More studies are needed in this domain in order to evaluate precisely the prevalence of pathological gambling in Lebanese university students. Copyright © 2012 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

Functional Assessment of Synoptic Pathology Reporting for Ovarian Cancer.

PubMed

Słodkowska, Janina; Cierniak, Szczepan; Patera, Janusz; Kopik, Jarosław; Baranowski, Włodzimierz; Markiewicz, Tomasz; Murawski, Piotr; Buda, Irmina; Kozłowski, Wojciech

2016-01-01

Ovarian cancer has one of the highest death/incidence rates and is commonly diagnosed at an advanced stage. In the recent WHO classification, new histotypes were classified which respond differently to chemotherapy. The e-standardized synoptic cancer pathology reports offer the clinicians essential and reliable information. The aim of our project was to develop an e-template for the standardized synoptic pathology reporting of ovarian carcinoma [based on the checklist of the College of American Pathologists (CAP) and the recent WHO/FIGO classification] to introduce a uniform and improved quality of cancer pathology reports. A functional and qualitative evaluation of the synoptic reporting was performed. An indispensable module for e-synoptic reporting was developed and integrated into the Hospital Information System (HIS). The electronic pathology system used a standardized structure with drop-down lists of defined elements to ensure completeness and consistency of reporting practices with the required guidelines. All ovarian cancer pathology reports (partial and final) with the corresponding glass slides selected from a 1-year current workflow were revised for the standard structured reports, and 42 tumors [13 borderline tumors and 29 carcinomas (mainly serous)] were included in the study. Analysis of the reports for completeness against the CAP checklist standard showed a lack of pTNM staging in 80% of the partial or final unstructured reports; ICD-O coding was missing in 83%. Much less frequently missed or unstated data were: ovarian capsule infiltration, angioinvasion and implant evaluation. The e-records of ovarian tumors were supplemented with digital macro- and micro-images and whole-slide images. The e-module developed for synoptic ovarian cancer pathology reporting was easily incorporated into HIS.CGM CliniNet and facilitated comprehensive reporting; it also provided open access to the database for concerned recipients. The e-synoptic pathology reports appeared more accurate, clear and conclusive than traditional narrative reports. Standardizing structured reporting and electronic tools allows open access and downstream utilization of pathology data for clinicians and tumor registries. © 2016 S. Karger AG, Basel.

Neural correlates of the impact of control on decision making in pathological gambling.

PubMed

Hudgens-Haney, Matthew E; Hamm, Jordan P; Goodie, Adam S; Krusemark, Elizabeth A; McDowell, Jennifer E; Clementz, Brett A

2013-02-01

Perceived control over a gambling outcome leads individuals to accept more and larger bets, increased risk-taking. Pathological gamblers, however, do not diminish risk-taking when control is absent, suggesting an illusion of control. To evaluate neural correlates of perceived control in gamblers, this study compared magnetoencephalography responses of 36 pathological (PG) and 36 non-pathological gamblers (NPG) during the Georgia Gambling Task. PGs exhibited greater activity in bilateral primary sensory regions. An interaction between pathology and control over the gambling task was observed bilaterally throughout dorsal and ventral visual processing streams, and lateral PFC. NPGs showed decreased activity when control was absent. Groups did not differ in response to potential bet cost. These findings provide neurophysiological evidence that PGs suffer from the pattern of risk-taking associated with perceived control, even when no control exists. They suggest that gambling pathology contributes to differential processing of gambling stimuli other than potential costs or rewards. Copyright © 2012 Elsevier B.V. All rights reserved.

Imbalance in the sensitivity to different types of rewards in pathological gambling.

PubMed

Sescousse, Guillaume; Barbalat, Guillaume; Domenech, Philippe; Dreher, Jean-Claude

2013-08-01

Pathological gambling is an addictive disorder characterized by a persistent and compulsive desire to engage in gambling activities. This maladaptive behaviour has been suggested to result from a decreased sensitivity to experienced rewards, regardless of reward type. Alternatively, pathological gambling might reflect an imbalance in the sensitivity to monetary versus non-monetary incentives. To directly test these two hypotheses, we examined how the brain reward circuit of pathological gamblers responds to different types of rewards. Using functional magnetic resonance imaging, we compared the brain responses of 18 pathological gamblers and 20 healthy control subjects while they engaged in a simple incentive task manipulating both monetary and visual erotic rewards. During reward anticipation, the ventral striatum of pathological gamblers showed a differential response to monetary versus erotic cues, essentially driven by a blunted reactivity to cues predicting erotic stimuli. This differential response correlated with the severity of gambling symptoms and was paralleled by a reduced behavioural motivation for erotic rewards. During reward outcome, a posterior orbitofrontal cortex region, responding to erotic rewards in both groups, was further recruited by monetary gains in pathological gamblers but not in control subjects. Moreover, while ventral striatal activity correlated with subjective ratings assigned to monetary and erotic rewards in control subjects, it only correlated with erotic ratings in gamblers. Our results point to a differential sensitivity to monetary versus non-monetary rewards in pathological gambling, both at the motivational and hedonic levels. Such an imbalance might create a bias towards monetary rewards, potentially promoting addictive gambling behaviour.

Practice of forensic medicine and pathology in Sri Lanka.

PubMed

Balachandra, A Thambirajah; Vadysinghe, Amal N; William, Anita L

2011-02-01

The practice of forensic medicine and pathology in Sri Lanka is based on the British model. Medical students during their third and fourth years receive approximately 50 hours of lectures and tutorials in forensic medicine and pathology and then undergo an examination. After completing an internship, these doctors are sent to various hospitals throughout Sri Lanka where they may be asked to perform medicolegal examinations on victims and suspects in rape cases, persons suspected of being under the influence of drugs and/or alcohol, and, injured live patients. As well, they may be asked to perform medicolegal autopsies. Depending upon their experience, some medical officers may be designated as judicial medical officers and appointed full time to do medicolegal work. Up until 1980, judicial medical officers with at least 2 years of work experience were allowed to obtain their postgraduate qualifications in the United Kingdom. However, since 1981 and the establishment of its own Postgraduate Institute of Medicine in Colombo, Sri Lanka, medical officers are offered 2 postgraduate programs in forensic medicine and pathology, a diploma in legal medicine and a doctorate in medicine (forensic medicine). After completing the doctorate in forensic medicine, doctors are allowed to train abroad for a further year in an approved center. Upon return they can then be appointed as consultant judicial medical officers. The practice of forensic medicine and pathology in Sri Lanka is unique and vibrant. However, due to the country's prevailing civil war, the practice of forensic medicine and pathology is suboptimal.

Assessment of the Radiation-Equivalent of Chemotherapy Contributions in 1-Phase Radio-chemotherapy Treatment of Muscle-Invasive Bladder Cancer

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

Plataniotis, George A., E-mail: george.plataniotis@nhs.net; Dale, Roger G.

2014-03-15

Purpose: To estimate the radiation equivalent of the chemotherapy contribution to observed complete response rates in published results of 1-phase radio-chemotherapy of muscle-invasive bladder cancer. Methods and Materials: A standard logistic dose–response curve was fitted to data from radiation therapy-alone trials and then used as the platform from which to quantify the chemotherapy contribution in 1-phase radio-chemotherapy trials. Two possible mechanisms of chemotherapy effect were assumed (1) a fixed radiation-independent contribution to local control; or (2) a fixed degree of chemotherapy-induced radiosensitization. A combination of both mechanisms was also considered. Results: The respective best-fit values of the independent chemotherapy-induced completemore » response (CCR) and radiosensitization (s) coefficients were 0.40 (95% confidence interval −0.07 to 0.87) and 1.30 (95% confidence interval 0.86-1.70). Independent chemotherapy effect was slightly favored by the analysis, and the derived CCR value was consistent with reports of pathologic complete response rates seen in neoadjuvant chemotherapy-alone treatments of muscle-invasive bladder cancer. The radiation equivalent of the CCR was 36.3 Gy. Conclusion: Although the data points in the analyzed radio-chemotherapy studies are widely dispersed (largely on account of the diverse range of chemotherapy schedules used), it is nonetheless possible to fit plausible-looking response curves. The methodology used here is based on a standard technique for analyzing dose-response in radiation therapy-alone studies and is capable of application to other mixed-modality treatment combinations involving radiation therapy.« less

Prolonged duration of response in lenvatinib responders with thyroid cancer.

PubMed

Gianoukakis, Andrew G; Dutcus, Corina E; Batty, Nicolas; Guo, Matthew; Baig, Mahadi

2018-06-01

We present an updated analysis of lenvatinib in radioiodine-refractory differentiated thyroid cancer (RR-DTC) with new duration of response (DOR) data unavailable for the primary analysis. In this randomized, double-blind, multicenter, placebo-controlled phase 3 study, patients ≥18 years old with measurable, pathologically confirmed RR-DTC with independent radiologic confirmation of disease progression within the previous 13 months were randomized 2:1 to oral lenvatinib 24 mg/day or placebo. The main outcome measures for this analysis are DOR and progression-free survival (PFS). The median DOR for all lenvatinib responders (patients with complete or partial responses; objective response rate: 60.2%; 95% confidence interval (CI) 54.2-66.1) was 30.0 months (95% CI 18.4-36.7) and was generally similar across subgroups. DOR was shorter in patients with greater disease burden and with brain and liver metastases. Updated median PFS was longer in the overall lenvatinib group vs placebo (19.4 vs 3.7 months; hazard ratio (HR) 0.24; 99% CI 0.17-0.35; nominal P  < 0.0001). In lenvatinib responders, median PFS was 33.1 months (95% CI 27.8-44.6) vs 7.9 months (95% CI 5.8-10.7) in non-responders. The median DOR of 30.0 months seen with patients who achieved complete or partial responses with lenvatinib (60.2%) demonstrates that lenvatinib responders can have prolonged, durable and clinically meaningful responses. Prolonged PFS (33.1 months) was also observed in these lenvatinib responders. © 2018 The authors.

Amplified Striatal Responses to Near-Miss Outcomes in Pathological Gamblers

PubMed Central

Sescousse, Guillaume; Janssen, Lieneke K; Hashemi, Mahur M; Timmer, Monique H M; Geurts, Dirk E M; ter Huurne, Niels P; Clark, Luke; Cools, Roshan

2016-01-01

Near-misses in gambling games are losing events that come close to a win. Near-misses were previously shown to recruit reward-related brain regions including the ventral striatum, and to invigorate gambling behavior, supposedly by fostering an illusion of control. Given that pathological gamblers are particularly vulnerable to such cognitive illusions, their persistent gambling behavior might result from an amplified striatal sensitivity to near-misses. In addition, animal studies have shown that behavioral responses to near-miss-like events are sensitive to dopamine, but this dopaminergic influence has not been tested in humans. To investigate these hypotheses, we recruited 22 pathological gamblers and 22 healthy controls who played a slot machine task delivering wins, near-misses and full-misses, inside an fMRI scanner. Each participant played the task twice, once under placebo and once under a dopamine D2 receptor antagonist (sulpiride 400 mg), in a double-blind, counter-balanced design. Participants were asked about their motivation to continue gambling throughout the task. Across all participants, near-misses elicited higher motivation to continue gambling and increased striatal responses compared with full-misses. Crucially, pathological gamblers showed amplified striatal responses to near-misses compared with controls. These group differences were not observed following win outcomes. In contrast to our hypothesis, sulpiride did not induce any reliable modulation of brain responses to near-misses. Together, our results demonstrate that pathological gamblers have amplified brain responses to near-misses, which likely contribute to their persistent gambling behavior. However, there is no evidence that these responses are influenced by dopamine. These results have implications for treatment and gambling regulation. PMID:27006113

Impact of the Addition of Carboplatin and/or Bevacizumab to Neoadjuvant Once-per-Week Paclitaxel Followed by Dose-Dense Doxorubicin and Cyclophosphamide on Pathologic Complete Response Rates in Stage II to III Triple-Negative Breast Cancer: CALGB 40603 (Alliance)

PubMed Central

Sikov, William M.; Berry, Donald A.; Perou, Charles M.; Singh, Baljit; Cirrincione, Constance T.; Tolaney, Sara M.; Kuzma, Charles S.; Pluard, Timothy J.; Somlo, George; Port, Elisa R.; Golshan, Mehra; Bellon, Jennifer R.; Collyar, Deborah; Hahn, Olwen M.; Carey, Lisa A.; Hudis, Clifford A.; Winer, Eric P.

2015-01-01

Purpose One third of patients with triple-negative breast cancer (TNBC) achieve pathologic complete response (pCR) with standard neoadjuvant chemotherapy (NACT). CALGB 40603 (Alliance), a 2 × 2 factorial, open-label, randomized phase II trial, evaluated the impact of adding carboplatin and/or bevacizumab. Patients and Methods Patients (N = 443) with stage II to III TNBC received paclitaxel 80 mg/m2 once per week (wP) for 12 weeks, followed by doxorubicin plus cyclophosphamide once every 2 weeks (ddAC) for four cycles, and were randomly assigned to concurrent carboplatin (area under curve 6) once every 3 weeks for four cycles and/or bevacizumab 10 mg/kg once every 2 weeks for nine cycles. Effects of adding these agents on pCR breast (ypT0/is), pCR breast/axilla (ypT0/isN0), treatment delivery, and toxicities were analyzed. Results Patients assigned to either carboplatin or bevacizumab were less likely to complete wP and ddAC without skipped doses, dose modification, or early discontinuation resulting from toxicity. Grade ≥ 3 neutropenia and thrombocytopenia were more common with carboplatin, as were hypertension, infection, thromboembolic events, bleeding, and postoperative complications with bevacizumab. Employing one-sided P values, addition of either carboplatin (60% v 44%; P = .0018) or bevacizumab (59% v 48%; P = .0089) significantly increased pCR breast, whereas only carboplatin (54% v 41%; P = .0029) significantly raised pCR breast/axilla. More-than-additive interactions between the two agents could not be demonstrated. Conclusion In stage II to III TNBC, addition of either carboplatin or bevacizumab to NACT increased pCR rates, but whether this will improve relapse-free or overall survival is unknown. Given results from recently reported adjuvant trials, further investigation of bevacizumab in this setting is unlikely, but the role of carboplatin could be evaluated in definitive studies, ideally limited to biologically defined patient subsets most likely to benefit from this agent. PMID:25092775

Web-based pathology practice examination usage.

PubMed

Klatt, Edward C

2014-01-01

General and subject specific practice examinations for students in health sciences studying pathology were placed onto a free public internet web site entitled web path and were accessed four clicks from the home web site menu. Multiple choice questions were coded into. html files with JavaScript functions for web browser viewing in a timed format. A Perl programming language script with common gateway interface for web page forms scored examinations and placed results into a log file on an internet computer server. The four general review examinations of 30 questions each could be completed in up to 30 min. The 17 subject specific examinations of 10 questions each with accompanying images could be completed in up to 15 min each. The results of scores and user educational field of study from log files were compiled from June 2006 to January 2014. The four general review examinations had 31,639 accesses with completion of all questions, for a completion rate of 54% and average score of 75%. A score of 100% was achieved by 7% of users, ≥90% by 21%, and ≥50% score by 95% of users. In top to bottom web page menu order, review examination usage was 44%, 24%, 17%, and 15% of all accessions. The 17 subject specific examinations had 103,028 completions, with completion rate 73% and average score 74%. Scoring at 100% was 20% overall, ≥90% by 37%, and ≥50% score by 90% of users. The first three menu items on the web page accounted for 12.6%, 10.0%, and 8.2% of all completions, and the bottom three accounted for no more than 2.2% each. Completion rates were higher for shorter 10 questions subject examinations. Users identifying themselves as MD/DO scored higher than other users, averaging 75%. Usage was higher for examinations at the top of the web page menu. Scores achieved suggest that a cohort of serious users fully completing the examinations had sufficient preparation to use them to support their pathology education.

Preoperative treatment with radiochemotherapy for locally advanced gastroesophageal junction cancer and unresectable locally advanced gastric cancer.

PubMed

Ratosa, Ivica; Oblak, Irena; Anderluh, Franc; Velenik, Vaneja; But-Hadzic, Jasna; Ermenc, Ajra Secerov; Jeromen, Ana

2015-06-01

To purpose of the study was to analyze the results of preoperative radiochemotherapy in patients with unresectable gastric or locoregionally advanced gastroesophageal junction (GEJ) cancer treated at a single institution. Between 1/2004 and 6/2012, 90 patients with locoregionally advanced GEJ or unresectable gastric cancer were treated with preoperative radiochemotherapy at the Institute of Oncology Ljubljana. Planned treatment schedule consisted of induction chemotherapy with 5-fluorouracil and cisplatin, followed by concomitant radiochemotherapy four weeks later. Three-dimensional conformal external beam radiotherapy was delivered by dual energy (6 and 15 MV) linear accelerator in 25 daily fractions of 1.8 Gy in 5 weeks with two additional cycles of chemotherapy repeated every 28 days. Surgery was performed 4-6 weeks after completing radiochemotherapy. Following the surgery, multidisciplinary advisory team reassessed patients for the need of adjuvant chemotherapy. The primary endpoints were histopathological R0 resection rate and pathological response rate. The secondary endpoints were toxicity of preoperative radiochemotherapy and survival. Treatment with preoperative radiochemotherapy was completed according to the protocol in 84 of 90 patients (93.3%). Twenty patients (22.2%) did not undergo the surgery because of the disease progression, serious comorbidity, poor performance status or still unresectable tumour. In 13 patients (14.4%) only exploration was performed because the tumour was assessed as unresectable or diffuse peritoneal carcinomatosis was established. Fifty-seven patients (63.4%) underwent surgery with the aim of complete removal of the tumour. Radical resection was achieved in 50 (55.6%) patients and the remaining seven (7.8%) patients underwent non-radical surgery (R1 in five and R2 in two patients). In this group of patients (n = 57), pathological complete response of tumour was achieved in five patients (5.6% of all treated patients or 8.8% of all operated patients). Down-staging was recorded in 49 patients (86%), in one patient (1.8%) the stage after radiochemotherapy was unchanged while in seven patients (12.3%) the pathological stage was higher than clinical, mainly due to higher pN stage. No death was recorded during preoperative radiochemotherapy. Most grade 3 and 4 toxicities were due to vomiting, nausea and bone marrow suppression (granulocytopenia). Twenty-six (45.6%) patients died due to GEJ or gastric carcinoma, one died because of septic shock following the surgery and a reason for two deaths was unknown. Twenty-eight patients (49.1%) were disease free at the time of analysis, while 29 patients (50.9%) developed the recurrence, mostly as distant metastases. At two years, locoregional control, disease-free survival, disease-specific survival and overall survival were 82.9%, 43.9%, 56.9% and 53.9%, respectively. Preoperative radiochemotherapy was feasible in our group of patients and had acceptable toxicity. Majority of patients achieved down-staging, allowing greater proportion of radical resections (R0), which are essential for patients' cure.

Relationship of Purported Measures of Pathological and Nonpathological Dissociation to Self-Reported Psychological Distress and Fantasy Immersion

ERIC Educational Resources Information Center

Levin, Ross; Spei, Ekaterina

2004-01-01

In order to investigate both the psychometric structure of the Dissociative Experiences Survey (DES) and the discriminant validity of the DES-Taxon (Waller, Putnam, & Carlson, 1996) as a specific marker of pathological dissociation, 376 non-clinical community based respondents completed the DES and a battery of psychopathology and imaginative…

Mitochondrial adaptations to physiological vs. pathological cardiac hypertrophy

PubMed Central

Abel, E. Dale; Doenst, Torsten

2011-01-01

Cardiac hypertrophy is a stereotypic response of the heart to increased workload. The nature of the workload increase may vary depending on the stimulus (repetitive, chronic, pressure, or volume overload). If the heart fully adapts to the new loading condition, the hypertrophic response is considered physiological. If the hypertrophic response is associated with the ultimate development of contractile dysfunction and heart failure, the response is considered pathological. Although divergent signalling mechanisms may lead to these distinct patterns of hypertrophy, there is some overlap. Given the close relationship between workload and energy demand, any form of cardiac hypertrophy will impact the energy generation by mitochondria, which are the key organelles for cellular ATP production. Significant changes in the expression of nuclear and mitochondrially encoded transcripts that impact mitochondrial function as well as altered mitochondrial proteome composition and mitochondrial energetics have been described in various forms of cardiac hypertrophy. Here, we review mitochondrial alterations in pathological and physiological hypertrophy. We suggest that mitochondrial adaptations to pathological and physiological hypertrophy are distinct, and we shall review potential mechanisms that might account for these differences. PMID:21257612

Major pathologic response to alectinib in ALK-rearranged adenocarcinoma of the lung.

PubMed

Imanishi, Naoko; Yoneda, Kazue; Taira, Akihiro; Ichiki, Yoshinobu; Sato, Naoko; Hisaoka, Masanori; Tanaka, Fumihiro

2018-03-09

Alectinib is a highly selective tyrosine kinase inhibitor of anaplastic lymphoma kinase (ALK) and provided a significantly prolonged progression-free survival compared with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) harboring rearrangements of the ALK gene. Here, we present the first surgical case of ALK-rearranged lung adenocarcinoma with major pathological response in resected specimens after treatment with alectinib. A 65-year-old female with clinical stage IIIA-N2 ALK-rearranged adenocarcinoma originating from the left lower lobe presented. Involvement of lower para-tracheal node was pathologically confirmed by endobronchial ultrasound-guided biopsy. Alectinib was prescribed, as the patient may not tolerate radiotherapy due to a mental illness. After 3 months' treatment with alectinib, a remarkable radiological and metabolic response was achieved. The patient did not tolerate further continuation of alectinib treatment, and surgery was performed without any morbidity. Only < 10% tumor cells were viable in all resected specimens, indicating major pathological response to alectinib. Salvage surgery after alectinib treatment may be safe and effective for initially unresectable NSCLC harboring ALK-rearrangements.

Complete remission in a colon cancer patient with a large, irresectable liver metastasis after XELOX/cetuximab/bevacizumab treatment.

PubMed

Weihrauch, Martin R; Stippel, Dirk; Fries, Jochen W U; Arnold, Dirk; Bovenschulte, Henning; Coutelle, Oliver; Hacker, Ulrich

2008-09-01

Stage IV colorectal cancer is usually an incurable disease. However, patients with resectable metastases have 5-year disease-free survival rates of up to 30%. Even with primarily irresectable disease, cure can be achieved in patients who become operable after neoadjuvant treatment. To improve the prognosis of these patients, highly effective neoadjuvant regimens need to be developed. Here, we report the case of a 62-year-old male patient who had been diagnosed with International Union against Cancer (UICC) stage III colon cancer 7 years previously and now presented with a large, irresectable liver metastasis and enlarged perihepatic lymph nodes. After neoadjuvant treatment with cetuximab, bevacizumab and XELOX, the patient showed a complete remission and underwent surgery. Histopathologically, the resected tissue and lymph nodes were free of residual tumor. To our knowledge, this is the first report of a complete pathological response in a patient with irresectable colorectal cancer after intensive chemotherapy/anti-EGFR/ VEGF antibody therapy. This combination regimen may help to improve the survival rates for patients with irresectable disease. Copyright 2008 S. Karger AG, Basel.

The influence of sleep on human hypothalamic-pituitary-adrenal (HPA) axis reactivity: A systematic review.

PubMed

van Dalfsen, Jens H; Markus, C Rob

2018-06-01

Inadequate sleep is highly prevalent and known to decline both physical- and mental health. Literature suggests that altered functioning of the hypothalamic-pituitary-adrenal (HPA) axis might underlie this association. This assumption is mainly based on changes in basal neuroendocrine activity and it is of equal importance to elucidate whether sleep may also influence HPA stress responsiveness. The present review provides a complete outline of recent human studies that have investigated how different aspects of sleep influence cortisol reactivity to laboratory stress. From the available data it can be concluded that both objective and subjective decrements in sleep quality potentiate the stress reactivity of the HPA axis. On the contrary, normal variations in sleep duration do not seem to influence cortisol stress responsiveness whereas excessive daytime sleepiness is associated with a blunting of the cortisol response. Given its well-established health consequences, sensitization of the HPA axis might well be a crucial component linking inadequate sleep to stress-related pathology. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mercury and neuromotor function among children in a rural town in Chile

PubMed Central

Huber, Stella Maria; Schomaker, Michael; Heumann, Christian; Schierl, Rudolf; Michalke, Bernhard; Jenni, Oskar G.; Caflisch, Jon; Muñoz, Daniel Moraga; von Ehrenstein, Ondine S.; Radon, Katja

2016-01-01

Background Mercury (Hg) exposure from artisanal gold mining has adverse effects on the neuromotor function in adults. However, few studies have examined this relationship in children. Objectives To investigate the impact of Hg exposure on children’s neuromotor function. Methods Cross-sectional data on Hg risk factors and demographics were collected from n = 288 children (response = 68.9%). Based on complete cases (CCs) (n = 130) and multiple imputations (n = 288), associations between fingernail Hg and four different neuromotor function components were calculated using multiple logistic regression adjusted for confounders. Results Of the children, 11.1, 14.9, 63.9, and 10.4% had pathologic pure motor skills, adaptive fine motor skills, adaptive gross motor skills, and static balance, respectively. No significant association between fingernail Hg and any neuromotor component was found. However, Hg burning in the household was significantly associated with children’s pathologic pure motor skills (OR 3.07 95% CI 1.03–9.18). Conclusion Elemental Hg exposure in the household might have adverse long-term effects on children’s pure motor skills. PMID:27078174

Predictions of the pathological response to neoadjuvant chemotherapy in patients with primary breast cancer using a data mining technique.

PubMed

Takada, M; Sugimoto, M; Ohno, S; Kuroi, K; Sato, N; Bando, H; Masuda, N; Iwata, H; Kondo, M; Sasano, H; Chow, L W C; Inamoto, T; Naito, Y; Tomita, M; Toi, M

2012-07-01

Nomogram, a standard technique that utilizes multiple characteristics to predict efficacy of treatment and likelihood of a specific status of an individual patient, has been used for prediction of response to neoadjuvant chemotherapy (NAC) in breast cancer patients. The aim of this study was to develop a novel computational technique to predict the pathological complete response (pCR) to NAC in primary breast cancer patients. A mathematical model using alternating decision trees, an epigone of decision tree, was developed using 28 clinicopathological variables that were retrospectively collected from patients treated with NAC (n = 150), and validated using an independent dataset from a randomized controlled trial (n = 173). The model selected 15 variables to predict the pCR with yielding area under the receiver operating characteristics curve (AUC) values of 0.766 [95 % confidence interval (CI)], 0.671-0.861, P value < 0.0001) in cross-validation using training dataset and 0.787 (95 % CI 0.716-0.858, P value < 0.0001) in the validation dataset. Among three subtypes of breast cancer, the luminal subgroup showed the best discrimination (AUC = 0.779, 95 % CI 0.641-0.917, P value = 0.0059). The developed model (AUC = 0.805, 95 % CI 0.716-0.894, P value < 0.0001) outperformed multivariate logistic regression (AUC = 0.754, 95 % CI 0.651-0.858, P value = 0.00019) of validation datasets without missing values (n = 127). Several analyses, e.g. bootstrap analysis, revealed that the developed model was insensitive to missing values and also tolerant to distribution bias among the datasets. Our model based on clinicopathological variables showed high predictive ability for pCR. This model might improve the prediction of the response to NAC in primary breast cancer patients.

Next-Generation Pathology.

PubMed

Caie, Peter D; Harrison, David J

2016-01-01

The field of pathology is rapidly transforming from a semiquantitative and empirical science toward a big data discipline. Large data sets from across multiple omics fields may now be extracted from a patient's tissue sample. Tissue is, however, complex, heterogeneous, and prone to artifact. A reductionist view of tissue and disease progression, which does not take this complexity into account, may lead to single biomarkers failing in clinical trials. The integration of standardized multi-omics big data and the retention of valuable information on spatial heterogeneity are imperative to model complex disease mechanisms. Mathematical modeling through systems pathology approaches is the ideal medium to distill the significant information from these large, multi-parametric, and hierarchical data sets. Systems pathology may also predict the dynamical response of disease progression or response to therapy regimens from a static tissue sample. Next-generation pathology will incorporate big data with systems medicine in order to personalize clinical practice for both prognostic and predictive patient care.

Immunohistochemical expression of CD-10, BCL-6 and MUM-1 antibodies and immediate clinical response in patients of diffuse large B-cell lymphomas after six cycles of chemotherapy.

PubMed

Hassan, Usman; Ishtiaq, Sheeba; Hussain, Mudassar

2014-10-01

To determine the expression of CD-10, BCL-6 and MUM-1 in patients with diffuse large B-cell lymphoma (DLBCL) and its association with immediate clinical response after six cycles of CHOP chemotherapy. Analytical study. Armed Forces Institute of Pathology (AFIP), Rawalpindi in collaboration with Nuclear medicine, Oncology and Radiotherapy Institute (NORI), Islamabad from September 2010 to September 2011. CD-10, BCL-6 and MUM-1 antibodies were applied on cases diagnosed as DLBCL. Immediate clinical response was noted after 6 cycles of chemotherapy with the help of oncologist and divided into complete response, partial response, stable disease and relapse/ progression. Patient's age, results of expression of CD-10, BCL-6 and MUM-1 and results of immediate clinical response to chemotherapy were noted. Regarding analysis of prognostic markers (CD-10, BCL-6 and MUM-1), chi-square test was used for immediate clinical response to chemotherapy in DLBCL. CD-10 was positive in 40% cases, BCL-6 in 58.7% cases and MUM-1 was positive in 46.7% cases. About 41.3% of patients showed complete response, 10.6% partial response, 17.3% stable disease and 30.8% showed relapse/progression. CD-10 expression in DLBCL was associated with better immediate clinical response (p=0.011) whereas MUM-1 expression in DLBCL was associated with poor immediate clinical response (p<0.0001). However, there was no statistically significant association of BCL-6 with immediate clinical response (p=0.22). DLBCL shows expression of CD-10, BCL-6 and MUM-1 in nearly fifty percent of the cases. CD-10 is associated with good whereas MUM is associated with poor response. However, there was no association of BCL-6 with immediate clinical response.

PC61 (Anti-CD25) Treatment Inhibits Influenza A Virus-Expanded Regulatory T Cells and Severe Lung Pathology during a Subsequent Heterologous Lymphocytic Choriomeningitis Virus Infection

PubMed Central

Kraft, Anke R. M.; Wlodarczyk, Myriam F.; Kenney, Laurie L.

2013-01-01

Prior immunity to influenza A virus (IAV) in mice changes the outcome to a subsequent lymphocytic choriomeningitis virus (LCMV) infection and can result in severe lung pathology, similar to that observed in patients that died of the 1918 H1N1 pandemic. This pathology is induced by IAV-specific memory CD8+ T cells cross-reactive with LCMV. Here, we discovered that IAV-immune mice have enhanced CD4+ Foxp3+ T-regulatory (Treg) cells in their lungs, leading us to question whether a modulation in the normal balance of Treg and effector T-cell responses also contributes to enhancing lung pathology upon LCMV infection of IAV-immune mice. Treg cell and interleukin-10 (IL-10) levels remained elevated in the lungs and mediastinal lymph nodes (mLNs) throughout the acute LCMV response of IAV-immune mice. PC61 treatment, used to decrease Treg cell levels, did not change LCMV titers but resulted in a surprising decrease in lung pathology upon LCMV infection in IAV-immune but not in naive mice. Associated with this decrease in pathology was a retention of Treg in the mLN and an unexpected partial clonal exhaustion of LCMV-specific CD8+ T-cell responses only in IAV-immune mice. PC61 treatment did not affect cross-reactive memory CD8+ T-cell proliferation. These results suggest that in the absence of IAV-expanded Treg cells and in the presence of cross-reactive memory, the LCMV-specific response was overstimulated and became partially exhausted, resulting in a decreased effector response. These studies suggest that Treg cells generated during past infections can influence the characteristics of effector T-cell responses and immunopathology during subsequent heterologous infections. Thus, in humans with complex infection histories, PC61 treatment may lead to unexpected results. PMID:24049180

Self-esteem and peer-perceived social status in early adolescence and prediction of eating pathology in young adulthood.

PubMed

Smink, Frédérique R E; van Hoeken, Daphne; Dijkstra, Jan Kornelis; Deen, Mathijs; Oldehinkel, Albertine J; Hoek, Hans W

2018-04-27

Self-esteem is implied as a factor in the development of eating disorders. In adolescence peers have an increasing influence. Support for the role of self-esteem in eating disorders is ambiguous and little is known about the influence of social status as judged by others. The present study investigates whether self-esteem and peer status in early adolescence are associated with eating pathology in young adulthood. This study is part of TRAILS, a longitudinal cohort study on mental health and social development from preadolescence into adulthood. At age 11, participants completed the Self-Perception Profile for Children, assessing global self-esteem and self-perceptions regarding social acceptance, physical appearance, and academic competence. At age 13, peer status among classmates was assessed regarding likeability, physical attractiveness, academic performance, and popularity in a subsample of 1,007 participants. The Eating Disorder Diagnostic Scale was administered at age 22. The present study included peer-nominated participants with completed measures of self-perception at age 11 and eating pathology at age 22 (N = 732; 57.8% female). In a combined model, self-perceived physical attractiveness at age 11 and peer popularity at age 13 were inversely correlated with eating pathology at 22 years, while likeability by peers at age 13 was positively related to eating pathology. Both self-perceptions and peer status in early adolescence are significant predictors of eating pathology in young adults. Specific measures of self-esteem and peer-perceived status may be more relevant to the prediction of eating pathology than a global measure of self-esteem. © 2018 The Authors International Journal of Eating Disorders Published by Wiley Periodicals, Inc.

Pathology reporting of malignant pleural mesothelioma first diagnosis: A population-based approach.

PubMed

Ascoli, Valeria; Minelli, Giada; Cozzi, Ilaria; Romeo, Elisa; Carnovale Scalzo, Caterina; Ancona, Laura; Forastiere, Francesco

2016-10-01

Accurate pathologic diagnosis and reporting in malignant pleural mesothelioma are essential for clinical care, and cancer registration. Practical guidelines for pathologists are provided in publications and textbooks but it is unclear how these recommendations are applied in routine practice. We investigated the characteristics of pathology reports, and the extent to which they meet guideline standards. We reviewed 819 pathology reports relating to a first diagnosis of malignant pleural mesothelioma. Data sources were a regional section of the Italian network of the Mesothelioma Registry (2001-2014) and a pathology archive (1990-2000). We evaluated tumor characteristics, the diagnosis field including terminology and immunohistochemistry (IHC) workup, and report completeness (the proportion of items recorded). We investigated also two IHC panels identified by the most used markers in current practical guidelines, one best suited for epithelioid mesotheliomas (combinations of at least 2 positive and at least 2 negative mesothelioma markers) and the other best suited for sarcomatoid mesotheliomas (positive mesothelioma markers plus cytokeratins). Reports (753 histology, 66 cytology, IHC-confirmed 86%) were 74% complete and always narrative. Missing data were related to clinical history (76%), tumor laterality (61%), specimen size (38%), and histological subtype (23%). The proportion of cases with IHC was higher for epithelioid (90%) than sarcomatoid mesothelioma (87%). Compliance to IHC recommendations was higher for epithelioid (59%) than sarcomatoid mesothelioma (11%). The mean number of stains was significantly higher for sarcomatoid than epithelioid mesothelioma (p<0.000; Kruskal-Wallis test). Our findings show that although guidelines are designed to improve actual reporting practices, there is ample room for improvement in their application to standardize the diagnosis of mesothelioma. Synoptic pathology reporting needs to be implemented to better utilize pathology information. Copyright © 2016 Elsevier GmbH. All rights reserved.

High-caloric and chocolate stimuli processing in healthy humans: an integration of functional imaging and electrophysiological findings.

PubMed

Asmaro, Deyar; Liotti, Mario

2014-01-10

There has been a great deal of interest in understanding how the human brain processes appetitive food cues, and knowing how such cues elicit craving responses is particularly relevant when current eating behavior trends within Westernized societies are considered. One substance that holds a special place with regard to food preference is chocolate, and studies that used functional magnetic resonance imaging (fMRI) and event-related potentials (ERPs) have identified neural regions and electrical signatures that are elicited by chocolate cue presentations. This review will examine fMRI and ERP findings from studies that used high-caloric food and chocolate cues as stimuli, with a focus on responses observed in samples of healthy participants, as opposed to those with eating-related pathology. The utility of using high-caloric and chocolate stimuli as a means of understanding the human reward system will also be highlighted, as these findings may be particularly important for understanding processes related to pathological overeating and addiction to illicit substances. Finally, research from our own lab that focused on chocolate stimulus processing in chocolate cravers and non-cravers will be discussed, as the approach used may help bridge fMRI and ERP findings so that a more complete understanding of appetitive stimulus processing in the temporal and spatial domains may be established.

Pharmacogenetics Biomarkers and Their Specific Role in Neoadjuvant Chemoradiotherapy Treatments: An Exploratory Study on Rectal Cancer Patients

PubMed Central

Dreussi, Eva; Cecchin, Erika; Polesel, Jerry; Canzonieri, Vincenzo; Agostini, Marco; Boso, Caterina; Belluco, Claudio; Buonadonna, Angela; Lonardi, Sara; Bergamo, Francesca; Gagno, Sara; De Mattia, Elena; Pucciarelli, Salvatore; De Paoli, Antonino; Toffoli, Giuseppe

2016-01-01

Background: Pathological complete response (pCR) to neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC) is still ascribed to a minority of patients. A pathway based-approach could highlight the predictive role of germline single nucleotide polymorphisms (SNPs). The primary aim of this study was to define new predictive biomarkers considering treatment specificities. Secondary aim was to determine new potential predictive biomarkers independent from radiotherapy (RT) dosage and cotreatment with oxaliplatin. Methods: Thirty germ-line SNPs in twenty-one genes were selected according to a pathway-based approach. Genetic analyses were performed on 280 LARC patients who underwent fluoropyrimidine-based CRT. The potential predictive role of these SNPs in determining pathological tumor response was tested in Group 1 (94 patients undergoing also oxaliplatin), Group 2 (73 patients treated with high RT dosage), Group 3 (113 patients treated with standard RT dosage), and in the pooled population (280 patients). Results: Nine new predictive biomarkers were identified in the three groups. The most promising one was rs3136228-MSH6 (p = 0.004) arising from Group 3. In the pooled population, rs1801133-MTHFR showed only a trend (p = 0.073). Conclusion: This exploratory study highlighted new potential predictive biomarkers of neoadjuvant CRT and underlined the importance to strictly define treatment peculiarities in pharmacogenetic analyses. PMID:27608007

Chronic obstructive pulmonary disease and asthma-associated Proteobacteria, but not commensal Prevotella spp., promote Toll-like receptor 2-independent lung inflammation and pathology.

PubMed

Larsen, Jeppe M; Musavian, Hanieh S; Butt, Tariq M; Ingvorsen, Camilla; Thysen, Anna H; Brix, Susanne

2015-02-01

Recent studies of healthy human airways have revealed colonization by a distinct commensal bacterial microbiota containing Gram-negative Prevotella spp. However, the immunological properties of these bacteria in the respiratory system remain unknown. Here we compare the innate respiratory immune response to three Gram-negative commensal Prevotella strains (Prevotella melaninogenica, Prevotella nanceiensis and Prevotella salivae) and three Gram-negative pathogenic Proteobacteria known to colonize lungs of patients with chronic obstructive pulmonary disease (COPD) and asthma (Haemophilus influenzae B, non-typeable Haemophilus influenzae and Moraxella catarrhalis). The commensal Prevotella spp. and pathogenic Proteobacteria were found to exhibit intrinsic differences in innate inflammatory capacities on murine lung cells in vitro. In vivo in mice, non-typeable H. influenzae induced severe Toll-like receptor 2 (TLR2)-independent COPD-like inflammation characterized by predominant airway neutrophilia, expression of a neutrophilic cytokine/chemokine profile in lung tissue, and lung immunopathology. In comparison, P. nanceiensis induced a diminished neutrophilic airway inflammation and no detectable lung pathology. Interestingly, the inflammatory airway response to the Gram-negative bacteria P. nanceiensis was completely TLR2-dependent. These findings demonstrate weak inflammatory properties of Gram-negative airway commensal Prevotella spp. that may make colonization by these bacteria tolerable by the respiratory immune system. © 2014 John Wiley & Sons Ltd.

Chronic obstructive pulmonary disease and asthma-associated Proteobacteria, but not commensal Prevotella spp., promote Toll-like receptor 2-independent lung inflammation and pathology

PubMed Central

Larsen, Jeppe M; Musavian, Hanieh S; Butt, Tariq M; Ingvorsen, Camilla; Thysen, Anna H; Brix, Susanne

2015-01-01

Recent studies of healthy human airways have revealed colonization by a distinct commensal bacterial microbiota containing Gram-negative Prevotella spp. However, the immunological properties of these bacteria in the respiratory system remain unknown. Here we compare the innate respiratory immune response to three Gram-negative commensal Prevotella strains (Prevotella melaninogenica, Prevotella nanceiensis and Prevotella salivae) and three Gram-negative pathogenic Proteobacteria known to colonize lungs of patients with chronic obstructive pulmonary disease (COPD) and asthma (Haemophilus influenzae B, non-typeable Haemophilus influenzae and Moraxella catarrhalis). The commensal Prevotella spp. and pathogenic Proteobacteria were found to exhibit intrinsic differences in innate inflammatory capacities on murine lung cells in vitro. In vivo in mice, non-typeable H. influenzae induced severe Toll-like receptor 2 (TLR2)-independent COPD-like inflammation characterized by predominant airway neutrophilia, expression of a neutrophilic cytokine/chemokine profile in lung tissue, and lung immunopathology. In comparison, P. nanceiensis induced a diminished neutrophilic airway inflammation and no detectable lung pathology. Interestingly, the inflammatory airway response to the Gram-negative bacteria P. nanceiensis was completely TLR2-dependent. These findings demonstrate weak inflammatory properties of Gram-negative airway commensal Prevotella spp. that may make colonization by these bacteria tolerable by the respiratory immune system. PMID:25179236

High-Caloric and Chocolate Stimuli Processing in Healthy Humans: An Integration of Functional Imaging and Electrophysiological Findings

PubMed Central

Asmaro, Deyar; Liotti, Mario

2014-01-01

There has been a great deal of interest in understanding how the human brain processes appetitive food cues, and knowing how such cues elicit craving responses is particularly relevant when current eating behavior trends within Westernized societies are considered. One substance that holds a special place with regard to food preference is chocolate, and studies that used functional magnetic resonance imaging (fMRI) and event-related potentials (ERPs) have identified neural regions and electrical signatures that are elicited by chocolate cue presentations. This review will examine fMRI and ERP findings from studies that used high-caloric food and chocolate cues as stimuli, with a focus on responses observed in samples of healthy participants, as opposed to those with eating-related pathology. The utility of using high-caloric and chocolate stimuli as a means of understanding the human reward system will also be highlighted, as these findings may be particularly important for understanding processes related to pathological overeating and addiction to illicit substances. Finally, research from our own lab that focused on chocolate stimulus processing in chocolate cravers and non-cravers will be discussed, as the approach used may help bridge fMRI and ERP findings so that a more complete understanding of appetitive stimulus processing in the temporal and spatial domains may be established. PMID:24434747

Translation and Validation of the Dutch Western Ontario Meniscal Evaluation Tool.

PubMed

van der Wal, Robert J P; Heemskerk, Bastiaan T J; van Arkel, Ewoud R A; Mokkink, Lidwine B; Thomassen, Bregje J W

2017-05-01

The aim of this study was to translate the Western Ontario Meniscal Evaluation Tool (WOMET) into Dutch, to evaluate the content validity, construct validity, reliability, and responsiveness, and to determine the minimal important change (MIC) of the Dutch version. The WOMET was translated into Dutch according to a standardized forward-backward translation protocol. A total of 86 patients (51 males, 35 females, median age 52 years [interquartile range, 43-60 years]) with isolated meniscal pathology were included. The WOMET was completed three times; at baseline, around 2 weeks, and after 3 months from the baseline. Knee injury and osteoarthritis outcome score, International Knee Documentation Committee subjective knee form, short-form 36, and an anchor question were also answered. There were good results for content validity (floor and ceiling effects [< 15%]), construct validity (79% of the predefined hypotheses were confirmed), internal consistency (Cronbach α = 0.87, 0.79, and 0.86 for each subscale score), test-retest reliability (intraclass correlation coefficient = 0.78 for total WOMET score), and responsiveness (79% of the predefined hypotheses were confirmed). The smallest detectable change and MIC for the Dutch WOMET are 20.5 and 14.7, respectively. The Dutch version of the WOMET is valid and reliable for assessing health-related quality of life in patients with meniscal pathology. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Physician scientist research pathway leading to certification by the American Board of Pathology.

PubMed

Weiss, Sharon W; Johnson, Rebecca L

2016-06-01

In 2014, the American Board of Pathology, in response to the pathology community, approved a physician scientist research pathway (PSRP). This brief report summarizes the history of and objectives for creating the physician scientist research pathway and the requirements of the American Board of Pathology for the certification of physician scientist research pathway trainees. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

[Role of locoregional radiation therapy in breast cancer patients with negative lymph nodes after preoperative chemotherapy and mastectomy. The Institut Curie-Hôpital René-Huguenin experience].

PubMed

Le Scodan, R; Bruant, S; Selz, J; Bollet, M-A; Daveau, C; de la Lande, B; Lerebours, F; Labib, A; Stevens, D

2011-12-01

Neoadjuvant chemotherapy generally induces significant changes in the pathological extent of disease and challenges the standard indications of adjuvant postmastectomy radiation therapy. We retrospectively evaluated the impact of postmastectomy radiation therapy in breast cancer patients with negative lymph nodes (pN0) after neoadjuvant chemotherapy. Among 1054 breast cancer patients treated with neoadjuvant chemotherapy in our institution between 1990 and 2004, 134 patients had pN0 status after neoadjuvant chemotherapy and mastectomy. Demographic data, tumor characteristics, metastatic sites, and treatments were prospectively recorded. The impact of postmastectomy radiation therapy on locoregional recurrence-free survival and overall survival was evaluated by multivariate analysis including known prognostic factors. Among 134 eligible patients, 78 patients (58.2%) received postmastectomy radiation therapy, and 56 patients (41.8%) did not. With a median follow-up time of 91.4 months, the 10-year locoregional recurrence-free survival and overall survival rates were 96.2% and 77.2% with postmastectomy radiation therapy and 86.8% and 87.7% without radiation therapy, respectively (no significant difference). In multivariate analysis, there was a trend towards poorer overall survival among patients who did not have a pathologically complete primary tumour response after neoadjuvant chemotherapy (hazard ratio [HR], 6.65; 95% CI, 0.82-54.12; P=0.076). Postmastectomy radiation therapy had no effect on either locoregional recurrence-free survival (HR, 0.37; 95% CI, 0.09-1.61; P=0.18) or overall survival (HR, 2.06; 95% CI, 0.71-6; P=0.18). There was a trend towards poorer overall survival among patients who did not have pathologically complete in-breast tumour response after neoadjuvant chemotherapy (HR, 6.65; 95% CI, 0.82-54.12; P=0.076). This retrospective study showed no increase in the risk of distant metastasis, locoregional recurrence or death when postmastectomy radiation therapy was omitted in breast cancer patients with pN0 status after neoadjuvant chemotherapy and mastectomy. Whether the omission of postmastectomy radiation therapy is acceptable for these patients should be addressed prospectively. Copyright © 2011 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

[MRI of the rotator cuff: evaluation of a new symptomatologic classification].

PubMed

Tavernier, T; Walch, G; Noël, E; Lapra, C; Bochu, M

1995-05-01

The different classifications use for the rotator cuff pathology seem to be incomplete. We propose a new classification with many advantages: 1) Differentiate the tendinopathy between less serious (grade 2A) and serious (grade 2B). 2) Recognize the intra-tendinous cleavage of the infra-spinatus associated with complete tear of the supra-spinatus. 3) Differentiate partial and complete tears of the supra-spinatus. We established this classification after a retrospective study of 42 patients operated on for a rotator cuff pathology. Every case had had a preoperative MRI. This classification is simple, reliable, especially for the associated intra tendinous cleavage.

Pathological documentation of complete elimination of Barrett's metaplasia following endoscopic multipolar electrocoagulation therapy

PubMed Central

Fennerty, M; Corless, C; Sheppard, B; Faigel, D; Lieberman, D; Sampliner, R

2001-01-01

The previous paradigm that Barrett's is an irreversible premalignant lesion has recently been challenged by a proliferation of reports documenting elimination of Barrett's by a variety of endoscopic techniques. Whether Barrett's is entirely eliminated is unknown as endoscopic biopsy samples the surface of the epithelium only. Numerous reports document underlying specialised columnar epithelium in many of these trials. Until now there have been no reports of pathological examination of the entire oesophagus as a specimen. This case documents complete elimination of intestinal metaplasia from the oesophagus and supports the biological plausibility of these research techniques.


Keywords: Barrett's oesophagus; endoscopy; multipolar electrocoagulation PMID:11413122

Retrospective review of positron emission tomography with contrast-enhanced computed tomography in the posttreatment setting in human papillomavirus-associated oropharyngeal carcinoma.

PubMed

Chan, Jason Y K; Sanguineti, Giuseppe; Richmon, Jeremy D; Marur, Shanthi; Gourin, Christine G; Koch, Wayne; Chung, Christine H; Quon, Harry; Bishop, Justin A; Aygun, Nafi; Agrawal, Nishant

2012-11-01

To determine the value of positron emission tomography (PET) with contrast-enhanced computed tomography (CT) in assessing the need for neck dissection by retrospectively reviewing the pathology reports of patients with human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (SCC). Retrospective cohort study. Tertiary medical center. Seventy-seven patients with HPV-related SCC. Seventy-seven consecutive patients with a diagnosis of HPV-related SCC who were treated with radiotherapy as the primary treatment between August 2007 and October 2010 were retrospectively evaluated for radiologic and pathologic rate of persistence of nodal metastasis after completion of definitive radiotherapy. Pretreatment and posttreatment imaging included contrast-enhanced CT and PET. Response to treatment was measured on CT, PET at standardized uptake value (SUV) thresholds of 2 and 2.5, and PET/CT by a neuroradiologist in a blinded fashion. Then, the pathology report of the patients who underwent neck dissections was reviewed for nodal status after resection and correlated with the imaging findings. Of the 77 patients, 67 met the study criteria, with an average follow-up PET/CT scan at 90.5 days after completion of radiotherapy. Ten patients did not undergo follow-up PET/CT imaging. Twenty patients underwent neck dissections after completion of radiation therapy. Of these 20 patients, 4 had persistent tumor and 16 did not have viable tumor. Using the final pathology report to correlate with imaging responses, CT had a negative predictive value (NPV) of 85.7% (95% CI, 48.7%-97.4%), PET with SUV thresholds of 2 had an NPV of 91.7% (95% CI, 64.6%-98.5%), PET with a cutoff SUV of 2.5 had an NPV of 85.7% (95% CI, 60.1%-96.0%), PET/CT with an SUV of 2 had an NPV of 100% (95% CI, 59.8%-100.0%), and PET/CT with an SUV of 2.5 had an NPV of 85.7% (95% CI, 48.7%-97.4%). The 47 patients who did not undergo neck dissection had a median follow-up of 26 months without an isolated neck failure. Analysis of all 67 patients in the cohort revealed the following values: CT had an NPV of 95.7% (95% CI, 85.8%-98.8%), PET with an SUV of 2 had an NPV of 98.2% (95% CI, 90.4%-99.7%), PET with an SUV of 2.5 had an NPV of 95.0% (95% CI, 86.3%-98.3%), PET/CT with an SUV of 2 had an NPV of 100.0% (95% CI, 92.0%-100.0%), and PET/CT with an SUV of 2.5 had an NPV of 95.7% (95% CI, 85.8%-98.8%). Positron emission tomography combined with contrast-enhanced CT has a better NPV than either imaging modality alone in patients with HPV-associated oropharyngeal SCC. Furthermore, PET/CT with an SUV threshold of 2 used in patients with HPV-related SCC offers an imaging modality with a high NPV that may obviate the need for unnecessary neck dissections.

A neurocognitive comparison of cognitive flexibility and response inhibition in gamblers with varying degrees of clinical severity.

PubMed

Odlaug, B L; Chamberlain, S R; Kim, S W; Schreiber, L R N; Grant, J E

2011-10-01

As a behavioral addiction with clinical and phenomenological similarities to substance addiction, recreational and pathological gambling represent models for studying the neurobiology of addiction, without the confounding deleterious brain effects which may occur from chronic substance abuse. A community sample of individuals aged 18-65 years who gamble was solicited through newspaper advertising. Subjects were grouped a priori into three groups (no-risk, at-risk, and pathological gamblers) based on a diagnostic interview. All subjects underwent a psychiatric clinical interview and neurocognitive tests assessing motor impulsivity and cognitive flexibility. Subjects with a current axis I disorder, history of brain injury/trauma, or implementation or dose changes of psychoactive medication within 6 weeks of study enrollment were excluded. A total of 135 no-risk, 69 at-risk and 46 pathological gambling subjects were assessed. Pathological gamblers were significantly older, and exhibited significant deficiencies in motor impulse control (stop-signal reaction times), response speed (median 'go' trial response latency) and cognitive flexibility [total intra-dimensional/extra-dimensional (IDED) errors] versus controls. The finding of impaired impulse control and cognitive flexibility was robust in an age-matched subgroup analysis of pathological gamblers. The no-risk and at-risk gambling groups did not significantly differ from each other on task performance. Impaired response inhibition and cognitive flexibility exist in people with pathological gambling compared with no-risk and at-risk gamblers. The early identification of such illness in adolescence or young adulthood may aid in the prevention of addiction onset of such disabling disorders.

The use of personalized biomarkers and liquid biopsies to monitor treatment response and disease recurrence in locally advanced rectal cancer after neoadjuvant chemoradiation.

PubMed

Carpinetti, Paola; Donnard, Elisa; Bettoni, Fabiana; Asprino, Paula; Koyama, Fernanda; Rozanski, Andrei; Sabbaga, Jorge; Habr-Gama, Angelita; Parmigiani, Raphael B; Galante, Pedro A F; Perez, Rodrigo O; Camargo, Anamaria A

2015-11-10

Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is the mainstay treatment for locally advanced rectal cancer. Variable degrees of tumor regression are observed after nCRT and alternative treatment strategies, including close surveillance without immediate surgery, have been investigated to spare patients with complete tumor regression from potentially adverse outcomes of radical surgery. However, clinical and radiological assessment of response does not allow accurate identification of patients with complete response. In addition, surveillance for recurrence is similarly important for these patients, as early detection of recurrence allows salvage resections and adjuvant interventions. We report the use of liquid biopsies and personalized biomarkers for monitoring treatment response to nCRT and detecting residual disease and recurrence in patients with rectal cancer. We sequenced the whole-genome of four rectal tumors to identify patient-specific chromosomal rearrangements that were used to monitor circulating tumor DNA (ctDNA) in liquid biopsies collected at diagnosis and during nCRT and follow-up. We compared ctDNA levels to clinical, radiological and pathological response to nCRT. Our results indicate that personalized biomarkers and liquid biopsies may not be sensitive for the detection of microscopic residual disease. However, it can be efficiently used to monitor treatment response to nCRT and detect disease recurrence, preceding increases in CEA levels and radiological diagnosis. Similar good results were observed when assessing tumor response to systemic therapy and disease progression. Our study supports the use of personalized biomarkers and liquid biopsies to tailor the management of rectal cancer patients, however, replication in a larger cohort is necessary to introduce this strategy into clinical practice.

Disrupted sensory gating in pathological gambling.

PubMed

Stojanov, Wendy; Karayanidis, Frini; Johnston, Patrick; Bailey, Andrew; Carr, Vaughan; Schall, Ulrich

2003-08-15

Some neurochemical evidence as well as recent studies on molecular genetics suggest that pathologic gambling may be related to dysregulated dopamine neurotransmission. The current study examined sensory (motor) gating in pathologic gamblers as a putative measure of endogenous brain dopamine activity with prepulse inhibition of the acoustic startle eye-blink response and the auditory P300 event-related potential. Seventeen pathologic gamblers and 21 age- and gender-matched healthy control subjects were assessed. Both prepulse inhibition measures were recorded under passive listening and two-tone prepulse discrimination conditions. Compared to the control group, pathologic gamblers exhibited disrupted sensory (motor) gating on all measures of prepulse inhibition. Sensory motor gating deficits of eye-blink responses were most profound at 120-millisecond prepulse lead intervals in the passive listening task and at 240-millisecond prepulse lead intervals in the two-tone prepulse discrimination task. Sensory gating of P300 was also impaired in pathologic gamblers, particularly at 500-millisecond lead intervals, when performing the discrimination task on the prepulse. In the context of preclinical studies on the disruptive effects of dopamine agonists on prepulse inhibition, our findings suggest increased endogenous brain dopamine activity in pathologic gambling in line with previous neurobiological findings.

Dissociation in undergraduate students: disruptions in executive functioning.

PubMed

Giesbrecht, Timo; Merckelbach, Harald; Geraerts, Elke; Smeets, Ellen

2004-08-01

The concept of dissociation refers to disruptions in attentional control. Attentional control is an executive function. Few studies have addressed the link between dissociation and executive functioning. Our study investigated this relationship in a sample of undergraduate students (N = 185) who completed the Dissociative Experiences Scale and the Random Number Generation Task. We found that minor disruptions in executive functioning were related to a subclass of dissociative experiences, notably dissociative amnesia and the Dissociative Experiences Scale Taxon. However, the two other subscales of the Dissociative Experiences Scale, measuring depersonalization and absorption, were unrelated to executive functioning. Our findings suggest that a failure to inhibit previous responses might contribute to the pathological memory manifestations of dissociation.

Neoadjuvant trials in ER+ breast cancer: A tool for acceleration of drug development and discovery

PubMed Central

Guerrero-Zotano, Angel L.; Arteaga, Carlos L.

2017-01-01

Neoadjuvant therapy trials offer an excellent strategy for drug development and discovery in breast cancer, particularly in triple negative and HER2-overexpressing subtypes, where pathologic complete response is a good surrogate of long term patient benefit. For estrogen receptor (ER)-positive breast cancers, however, use of this strategy has been challenging because of the lack of validated surrogates of long term efficacy and the overall good prognosis of the majority of patients with this cancer subtype. We review below the clinical benefits of neodjuvant endocrine therapy for ER+/HER2-negative breast cancer, its use and limitations for drug development, prioritization of adjuvant and metastatic trials, and biomarker discovery. PMID:28495849

Clinico-pathological correlation in adenylate kinase 5 autoimmune limbic encephalitis

PubMed Central

Ng, Adeline S.L.; Kramer, Joel; Centurion, Alejandro; Dalmau, Josep; Huang, Eric; Cotter, Jennifer A.; Geschwind, Michael D.

2016-01-01

Autoantibodies associated with autoimmune limbic encephalitis (ALE) have been well-characterized, with intracellular neuronal antibodies being less responsive to immunotherapy than antibodies to cell surface antigens. Adenylate kinase 5 (AK5) is a nucleoside monophosphate kinase vital for neuronal-specific metabolism and is located intracellularly in the cytosol and expressed exclusively in the brain. Antibodies to AK5 had been previously identified but were not known to be associated with human disease prior to the report of two patients with AK5-related ALE (Tuzun et al., 2007). We present the complete clinical picture for one of these patients and the first reported neuropathology for AK5 ALE. PMID:26439959

IL-10 restrains IL-17 to limit lung pathology characteristics following pulmonary infection with Francisella tularensis live vaccine strain.

PubMed

Slight, Samantha R; Monin, Leticia; Gopal, Radha; Avery, Lyndsay; Davis, Marci; Cleveland, Hillary; Oury, Tim D; Rangel-Moreno, Javier; Khader, Shabaana A

2013-11-01

IL-10 production during intracellular bacterial infections is generally thought to be detrimental because of its role in suppressing protective T-helper cell 1 (Th1) responses. Francisella tularensis is a facultative intracellular bacterium that activates both Th1 and Th17 protective immune responses. Herein, we report that IL-10-deficient mice (Il10(-/-)), despite having increased Th1 and Th17 responses, exhibit increased mortality after pulmonary infection with F. tularensis live vaccine strain. We demonstrate that the increased mortality observed in Il10(-/-)-infected mice is due to exacerbated IL-17 production that causes increased neutrophil recruitment and associated lung pathology. Thus, although IL-17 is required for protective immunity against pulmonary infection with F. tularensis live vaccine strain, its production is tightly regulated by IL-10 to generate efficient induction of protective immunity without mediating pathology. These data suggest a critical role for IL-10 in maintaining the delicate balance between host immunity and pathology during pulmonary infection with F. tularensis live vaccine strain. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

The hamster (Mesocricetus auratus) as an experimental model of toxocariasis: histopathological, immunohistochemical, and immunoelectron microscopic findings.

PubMed

da Silva, Ana Maria Gonçalves; Chieffi, Pedro Paulo; da Silva, Wellington Luiz Ferreira; Kanashiro, Edite Hatsumi Yamashiro; Rubinsky-Elefant, Guita; Cunha-Neto, Edécio; Mairena, Eliane Conti; De Brito, Thales

2015-03-01

Toxocariasis is a globally distributed parasitic infection caused by the larval stage of Toxocara spp. The typical natural hosts of the parasite are dogs and cats, but humans can be infected by the larval stage of the parasite after ingesting embryonated eggs in soil or from contaminated hands or fomites. The migrating larvae are not adapted to complete their life cycle within accidental or paratenic hosts like humans and laboratory animals, respectively, but they are capable of invading viscera or other tissues where they may survive and induce disease. In order to characterize hamsters (Mesocricetus auratus) as a model for Toxocara canis infection, histopathological and immunohistochemistry procedures were used to detect pathological lesions and the distribution of toxocaral antigens in the liver, lungs, and kidneys of experimentally infected animals. We also attempted to characterize the immunological parameters of the inflammatory response and correlate them with the histopathological findings. In the kidney, a correlation between glomerular changes and antigen deposits was evaluated using immunoelectron microscopy. The hamster is an adequate model of experimental toxocariasis for short-term investigations and has a good immunological and pathological response to the infection. Lung and liver manifestations of toxocariasis in hamsters approximated those in humans and other experimental animal models. A mixed Th2 immunological response to T. canis infection was predominant. The hamster model displayed a progressive rise of anti-toxocaral antibodies with the formation of immune complexes. Circulating antigens, immunoglobulin, and complement deposits were detected in the kidney without the development of a definite immune complex nephropathy.

Irf8-Regulated Genomic Responses Drive Pathological Inflammation during Cerebral Malaria

PubMed Central

Radovanovic, Irena; Tam, Mifong; MacMicking, John D.; Stevenson, Mary M.; Gros, Philippe

2013-01-01

Interferon Regulatory Factor 8 (IRF8) is required for development, maturation and expression of anti-microbial defenses of myeloid cells. BXH2 mice harbor a severely hypomorphic allele at Irf8 (Irf8R294C) that causes susceptibility to infection with intracellular pathogens including Mycobacterium tuberculosis. We report that BXH2 are completely resistant to the development of cerebral malaria (ECM) following Plasmodium berghei ANKA infection. Comparative transcriptional profiling of brain RNA as well as chromatin immunoprecipitation and high-throughput sequencing (ChIP-seq) was used to identify IRF8-regulated genes whose expression is associated with pathological acute neuroinflammation. Genes increased by infection were strongly enriched for IRF8 binding sites, suggesting that IRF8 acts as a transcriptional activator in inflammatory programs. These lists were enriched for myeloid-specific pathways, including interferon responses, antigen presentation and Th1 polarizing cytokines. We show that inactivation of several of these downstream target genes (including the Irf8 transcription partner Irf1) confers protection against ECM. ECM-resistance in Irf8 and Irf1 mutants is associated with impaired myeloid and lymphoid cells function, including production of IL12p40 and IFNγ. We note strong overlap between genes bound and regulated by IRF8 during ECM and genes regulated in the lungs of M. tuberculosis infected mice. This IRF8-dependent network contains several genes recently identified as risk factors in acute and chronic human inflammatory conditions. We report a common core of IRF8-bound genes forming a critical inflammatory host-response network. PMID:23853600

Treatment of AIDS related non-Hodgkin's lymphoma with combination mitoguazone dihydrochloride and low dose CHOP chemotherapy: results of a phase II study.

PubMed

Tulpule, Anil; Espina, Byron M; Pedro Santabarbara, A B; Palmer, Maria; Schiflett, Joanne; Boswell, William; Smith, Susan; Levine, Alexandra M

2004-01-01

To evaluate the response and side effects of combination therapy with low dose CHOP chemotherapy and mitoguazone dihydrochloride in patients with non-Hodgkin's lymphoma associated with the acquired immunodeficiency syndrome (AIDS-NHL). Eighteen patients newly diagnosed with intermediate or high-grade AIDS-NHL were treated with low dose CHOP as follows: day 1, cyclophosphamide 350 mg/m(2), intravenously (IV); doxorubicin 25mg/m(2) IV; vincristine 2mg IV; and prednisone 100mg given orally on days 1 through 5. In addition, mitoguazone dihydrochloride was given at a dose of 600 mg/m(2) IV on days 1 and 15 of each 28-day treatment cycle. Seventeen males and one female patient were accrued. Twelve patients had high-grade pathologies while the remainder had an intermediate grade pathology (diffuse large cell). The median CD4+ lymphocyte count was 98/dl (range 1-924). Three patients (17%) reported an AIDS-defining illness prior to lymphoma diagnosis. Of 14 evaluable patients, 6 (43%) achieved a complete remission and 5 (35%) a partial remission. The median failure free and overall survival times were 6.5 and 8.4 months, respectively. Major toxicity was hematologic with grade 3 or 4 neutropenia in 72%; two patients died of neutropenic sepsis. Mitoguazone in combination with low dose CHOP is a safe regimen, associated with a response rate of 79% (CR 43%, PR 36%, 95% CI=49-95%). These preliminary results suggest no major improvement in terms of response over use of CHOP without mitoguazone.

High production of pro-inflammatory cytokines by maternal blood mononuclear cells is associated with reduced maternal malaria but increased cord blood infection.

PubMed

Dobaño, Carlota; Berthoud, Tamara; Manaca, Maria Nelia; Nhabomba, Augusto; Guinovart, Caterina; Aguilar, Ruth; Barbosa, Arnoldo; Groves, Penny; Rodríguez, Mauricio H; Jimenez, Alfons; Quimice, Lazaro M; Aponte, John J; Ordi, Jaume; Doolan, Denise L; Mayor, Alfredo; Alonso, Pedro L

2018-05-10

Increased susceptibility to malaria during pregnancy is not completely understood. Cellular immune responses mediate both pathology and immunity but the effector responses involved in these processes have not been fully characterized. Maternal and fetal cytokine and chemokine responses to malaria at delivery, and their association with pregnancy and childhood outcomes, were investigated in 174 samples from a mother and child cohort from Mozambique. Peripheral and cord mononuclear cells were stimulated with Plasmodium falciparum lysate and secretion of IL-12p70, IFN-γ, IL-2, IL-10, IL-8, IL-6, IL-4, IL-5, IL-1β, TNF, TNF-β was quantified in culture supernatants by multiplex flow cytometry while cellular mRNA expression of IFN-γ, TNF, IL-2, IL-4, IL-6, IL-10 and IL-13 was measured by quantitative PCR. Higher concentrations of IL-6 and IL-1β were associated with a reduced risk of P. falciparum infection in pregnant women (p < 0.049). Pro-inflammatory cytokines IL-6, IL-1β and TNF strongly correlated among themselves (ρ > 0.5, p < 0.001). Higher production of IL-1β was significantly associated with congenital malaria (p < 0.046) and excessive TNF was associated with peripheral infection and placental lesions (p < 0.044). Complex network of immuno-pathological cytokine mechanisms in the placental and utero environments showed a potential trade-off between positive and negative effects on mother and newborn susceptibility to infection.

The combination of two Sle2 lupus-susceptibility loci and Cdkn2c deficiency leads to T cell-mediated pathology in B6.Faslpr mice

PubMed Central

Xu, Zhiwei; Croker, Byron P.; Morel, Laurence

2013-01-01

The NZM2410 Sle2c1 lupus susceptibility locus is responsible for the expansion of the B1a cell compartment and for the induction of T-cell induced renal and skin pathology on a CD95 deficient (Faslpr)-background. We have previously shown that deficiency in cyclin-dependent kinase inhibitor p18INK4c (p18) was responsible for the B1a cell expansion but was not sufficient to account for the pathology in B6.lpr mice. This study was designed to map the additional Sle2c1 loci responsible for autoimmune pathology when co-expressed with CD95 deficiency. The production, fine-mapping and phenotypic characterization of five recombinant intervals indicated that three interacting sub-loci were responsive for inducting autoimmune pathogenesis in B6.lpr mice. One of these sub-loci corresponds most likely to p18-deficiency. Another major locus mapping to a 2 Mb region at the telomeric end of Sle2c1 is necessary to both renal and skin pathology. Finally, a third locus centromeric to p18 enhances the severity of lupus nephritis. These results provide new insights into the genetic interactions leading to SLE disease presentation, and represent a major step towards the identification of novel susceptibility genes involved in T-cell mediated organ damage. PMID:23698709

Clinicopathologic characteristics and outcome of childhood and adolescent Ewing's sarcoma in center of Iran.

PubMed

Akhavan, A; Binesh, F; Hashemi, A; Shamshiri, H

2014-01-01

Ewing's sarcoma family is a group of small round cells tumors. The aim of this study is to evaluate clinicopathologic characteristics and outcome of Ewing's sarcoma in children and adolescents in Yazd, Iran. All patients under 19 years with documented pathology of Ewing's sarcoma family tumor who referred to Shahid Ramazanzadeh Radiotherapy center between 2002 to 2010 were enrolled in this retrospective study. Overall survival and disease free survival and prognostic factors were evaluated. Among approximately 80,000 patients who referred to Shahid Sadoughi pathology department, over an 8-year period, the total number of patients with Ewing sarcoma was 32, of which, 18 cases were under the age 19 . The mean age was 13.72 years. Five patients (27.8%) had metastatic disease at the time of diagnosis. Complete response had been achieved in 8 (44.4%) of the patients. Local recurrence occurred in 4 (22.2%) of the patients. During the follow up 13 (72.2%) of the patients showed metastases. The mean overall survival was 34.79 months (95% CI: 22.27-47.32) .One, two, four and five year survival was 72%, 39%, 25% and 17% respectively. Complete remission occurred in 10 patients (63.6%). A trend of better overall survival was found in these patients (p=0. 55). When the brain and bone metastases occurred, the overall survival decreased significantly (p=0. 003 ). The overall survival rate of Ewing's sarcoma is very low in comparison with other parts of the world.

Multicolor fluorescent intravital live microscopy (FILM) for surgical tumor resection in a mouse xenograft model.

PubMed

Thurber, Greg M; Figueiredo, Jose L; Weissleder, Ralph

2009-11-30

Complete surgical resection of neoplasia remains one of the most efficient tumor therapies. However, malignant cell clusters are often left behind during surgery due to the inability to visualize and differentiate them against host tissue. Here we establish the feasibility of multicolor fluorescent intravital live microscopy (FILM) where multiple cellular and/or unique tissue compartments are stained simultaneously and imaged in real time. Theoretical simulations of imaging probe localization were carried out for three agents with specificity for cancer cells, stromal host response, or vascular perfusion. This transport analysis gave insight into the probe pharmacokinetics and tissue distribution, facilitating the experimental design and allowing predictions to be made about the localization of the probes in other animal models and in the clinic. The imaging probes were administered systemically at optimal time points based on the simulations, and the multicolor FILM images obtained in vivo were then compared to conventional pathological sections. Our data show the feasibility of real time in vivo pathology at cellular resolution and molecular specificity with excellent agreement between intravital and traditional in vitro immunohistochemistry. Multicolor FILM is an accurate method for identifying malignant tissue and cells in vivo. The imaging probes distributed in a manner similar to predictions based on transport principles, and these models can be used to design future probes and experiments. FILM can provide critical real time feedback and should be a useful tool for more effective and complete cancer resection.

Greater occipital nerve neuralgia caused by pathological arterial contact: treatment by surgical decompression.

PubMed

Cornely, Christiane; Fischer, Marius; Ingianni, Giulio; Isenmann, Stefan

2011-04-01

Occipital nerve neuralgia is a rare cause of severe headache, and may be difficult to treat. We report the case of a patient with occipital nerve neuralgia caused by pathological contact of the nerve with the occipital artery. The pain was refractory to medical treatment. Surgical decompression yielded complete remission. © 2010 American Headache Society.

Phase II study of neoadjuvant treatment with doxorubicin, docetaxel, and capecitabine (ATX) in locally advanced or inflammatory breast cancer.

PubMed

Manga, Gumersindo Pérez; Shahi, Parham Khosravi; Ureña, Miguel Méndez; Pereira, Rosa Quiben; Plaza, María Isabel Palomero; Peron, Yann Izarzugaza; Val, Ricardo González Del; Carrión, Joaquín Belón; Cañón, Esperanza Pérez; Alfonso, Pilar García

2010-07-01

Pathologic complete response (pCR) after preoperative systemic chemotherapy (PSCh) is associated with better outcome in locally advanced breast cancer (LABC). PSCh included: doxorubicin (A) 50 mg/m(2) i.v. on day 1; docetaxel (T) 30 mg/m(2) i.v. on days 1, 8 and 15; and capecitabine (X) 1,500 mg/m(2)/day p.o. on days 1-14, in a 4-week course repeated for up to four cycles (ATX), followed by surgery. The primary end point of this study was to evaluate the pCR rate. Secondary endpoints included clinical response rate, disease-free survival (DFS), overall survival (OS), and the toxicity profile. A total of 60 patients were included in the analysis. Median age was 49 years, and 63.3% of patients were hormone receptor positive. The median number of cycles of PSCh was four (95% CI: 3-4). Five patients (8.3%) achieved pCR in both breast and nodes, and 16.7% reached pCR only in nodes. The clinical response rate was 77% (27% complete response), but only 18% of the patients underwent conservative surgery. With a median follow-up of 20 months, 3-year DFS and OS were 76 and 90%, respectively. Grade III/IV toxicity included neutropenia (74%), febrile neutropenia (9%), mucositis (12%), and diarrhea (12%). ATX every 28 days for four cycles is associated with a modest activity (low pCR rate) in the neoadjuvant setting of LABC.

Selective Memory to Apoptotic Cell-Derived Self-Antigens with Implications for Systemic Lupus Erythematosus Development.

PubMed

Duhlin, Amanda; Chen, Yunying; Wermeling, Fredrik; Sedimbi, Saikiran K; Lindh, Emma; Shinde, Rahul; Halaby, Marie Jo; Kaiser, Ylva; Winqvist, Ola; McGaha, Tracy L; Karlsson, Mikael C I

2016-10-01

Autoimmune diseases are characterized by pathogenic immune responses to self-antigens. In systemic lupus erythematosus (SLE), many self-antigens are found in apoptotic cells (ACs), and defects in removal of ACs from the body are linked to a risk for developing SLE. This includes pathological memory that gives rise to disease flares. In this study, we investigated how memory to AC-derived self-antigens develops and the contribution of self-memory to the development of lupus-related pathology. Multiple injections of ACs without adjuvant into wild-type mice induce a transient primary autoimmune response without apparent anti-nuclear Ab reactivity or kidney pathology. Interestingly, as the transient Ab response reached baseline, a single boost injection fully recalled the immune response to ACs, and this memory response was furthermore transferable into naive mice. Additionally, the memory response contains elements of pathogenicity, accompanied by selective memory to selective Ags. Thus, we provide evidence for a selective self-memory that underlies progression of the response to self-antigens with implications for SLE development therapy. Copyright © 2016 by The American Association of Immunologists, Inc.

The national DBS brain tissue network pilot study: need for more tissue and more standardization.

PubMed

Vedam-Mai, V; Krock, N; Ullman, M; Foote, K D; Shain, W; Smith, K; Yachnis, A T; Steindler, D; Reynolds, B; Merritt, S; Pagan, F; Marjama-Lyons, J; Hogarth, P; Resnick, A S; Zeilman, P; Okun, M S

2011-08-01

Over 70,000 DBS devices have been implanted worldwide; however, there remains a paucity of well-characterized post-mortem DBS brains available to researchers. We propose that the overall understanding of DBS can be improved through the establishment of a Deep Brain Stimulation-Brain Tissue Network (DBS-BTN), which will further our understanding of DBS and brain function. The objectives of the tissue bank are twofold: (a) to provide a complete (clinical, imaging and pathological) database for DBS brain tissue samples, and (b) to make available DBS tissue samples to researchers, which will help our understanding of disease and underlying brain circuitry. Standard operating procedures for processing DBS brains were developed as part of the pilot project. Complete data files were created for individual patients and included demographic information, clinical information, imaging data, pathology, and DBS lead locations/settings. 19 DBS brains were collected from 11 geographically dispersed centers from across the U.S. The average age at the time of death was 69.3 years (51-92, with a standard deviation or SD of 10.13). The male:female ratio was almost 3:1. Average post-mortem interval from death to brain collection was 10.6 h (SD of 7.17). The DBS targets included: subthalamic nucleus, globus pallidus interna, and ventralis intermedius nucleus of the thalamus. In 16.7% of cases the clinical diagnosis failed to match the pathological diagnosis. We provide neuropathological findings from the cohort, and perilead responses to DBS. One of the most important observations made in this pilot study was the missing data, which was approximately 25% of all available data fields. Preliminary results demonstrated the feasibility and utility of creating a National DBS-BTN resource for the scientific community. We plan to improve our techniques to remedy omitted clinical/research data, and expand the Network to include a larger donor pool. We will enhance sample preparation to facilitate advanced molecular studies and progenitor cell retrieval.

How Useful Are Indices of Personality Pathology when Assessing Domestic Violence Perpetrators?

ERIC Educational Resources Information Center

Gibbons, Peter; Collins, Marjorie; Reid, Corinne

2011-01-01

There has been considerable debate about profiling personality pathology when assessing and treating male perpetrators of domestic violence (DV). This study used the Millon Clinical Multiaxial Inventory (MCMI-III) to explore the severity and diversity of male perpetrator personality pathology and response bias in a group of DV perpetrators being…

Strategies for laboratory cost containment and for pathologist shortage: centralised pathology laboratories with microwave-stimulated histoprocessing and telepathology.

PubMed

Leong, Anthony S Y; Leong, F Joel W M

2005-02-01

The imposition of laboratory cost containment, often from external forces, dictates the necessity to develop strategies to meet laboratory cost savings. In addition, the national and worldwide shortage of anatomical pathologists makes it imperative to examine our current practice and laboratory set-ups. Some of the strategies employed in other areas of pathology and laboratory medicine include improvements in staff productivity and the adoption of technological developments that reduce manual intervention. However, such opportunities in anatomical pathology are few and far between. Centralisation has been an effective approach in bringing economies of scale, the adoption of 'best practices' and the consolidation of pathologists, but this has not been possible in anatomical pathology because conventional histoprocessing takes a minimum of 14 hours and clinical turnaround time requirements necessitate that the laboratory and pathologist be in proximity and on site. While centralisation of laboratories for clinical chemistry, haematology and even microbiology has been successful in Australia and other countries, the essential requirements for anatomical pathology laboratories are different. In addition to efficient synchronised courier networks, a method of ultra-rapid tissue processing and some expedient system of returning the prepared tissue sections to the remote laboratory are essential to maintain the turnaround times mandatory for optimal clinical management. The advent of microwave-stimulated tissue processing that can be completed in 30-60 minutes and the immediate availability of compressed digital images of entire tissue sections via telepathology completes the final components of the equation necessary for making centralised anatomical pathology laboratories a reality.

Association between radiation dose and pathological complete response after preoperative radiochemotherapy in esophageal squamous cell cancer.

PubMed

Ordu, Arif Deniz; Nieder, Carsten; Geinitz, Hans; Scherer, Vera; Kup, Philipp Günther; Schuster, Tibor; Combs, Stephanie E; Fakhrian, Khashayar

2014-12-01

This study was undertaken to examine the impact of radiation dose on pathological complete response (pCR) rates following neoadjuvant radiochemotherapy (N-RCT) for squamous cell esophageal cancer (ESCC). From 1988 to 2011, 218 patients were treated with 30-30.6 Gy (1.8-2 Gy per fraction), 39.6-40 Gy (1.8-2 Gy per fraction) or 44-45 Gy (1.8-2 Gy per fraction) and concomitant cisplatin ± 5-fluorouracil (5-FU), oxaliplatin + 5-FU or 5-FU alone. The most commonly used concomitant chemotherapy was continuous infusion of 5-FU-alone with a dose of 300 mg/m(2)/day during the whole course of treatment (n=111). To eliminate the dispersing effect of potentially different efficacy levels of these drug regimens on pCR, we excluded patients with regimens other than 5-FU-alone. Histomorphological regression grade 1a (0% residual tumor), 1b (<10% residual tumor), 2 (10-50% residual tumor) and 3 (>50% residual tumor) was observed in 26 (23%), 24 (22%), 36 (32%) and 25 (23%) patients, respectively. pCR was observed in 9 out of 71 (13%) patients treated with 30 Gy-30.6 Gy, 13 of 34 (38%) patients treated with 39.6-40 Gy and 4 of 6 (67%) patients treated with 44-45 Gy (p=0.001). Median follow-up time from the start of N-RCT was 191 months (range=2-262 months). The estimated 5-year overall survival (OS) was 33% for the whole cohort. OS at 5 years was 58% for patients with pCR compared to 25% for patients with less favorable response to N-RCT (p=0.009), respectively. The dose of radiation correlates significantly with the likelihood of achieving a pCR in stage II/III squamous cell esophageal cancer patients. Prospective randomized trials are required to definitively evaluate the impact of application of higher radiation doses on efficacy and safety/tolerability in the context of N-RCT on the clinical outcomes. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Immunodominance: a new hypothesis to explain parasite escape and host/parasite equilibrium leading to the chronic phase of Chagas' disease?

PubMed

Rodrigues, M M; Alencar, B C G de; Claser, C; Tzelepis, F

2009-03-01

Intense immune responses are observed during human or experimental infection with the digenetic protozoan parasite Trypanosoma cruzi. The reasons why such immune responses are unable to completely eliminate the parasites are unknown. The survival of the parasite leads to a parasite-host equilibrium found during the chronic phase of chagasic infection in most individuals. Parasite persistence is recognized as the most likely cause of the chagasic chronic pathologies. Therefore, a key question in Chagas' disease is to understand how this equilibrium is established and maintained for a long period. Understanding the basis for this equilibrium may lead to new approaches to interventions that could help millions of individuals at risk for infection or who are already infected with T. cruzi. Here, we propose that the phenomenon of immunodominance may be significant in terms of regulating the host-parasite equilibrium observed in Chagas' disease. T. cruzi infection restricts the repertoire of specific T cells generating, in some cases, an intense immunodominant phenotype and in others causing a dramatic interference in the response to distinct epitopes. This immune response is sufficiently strong to maintain the host alive during the acute phase carrying them to the chronic phase where transmission usually occurs. At the same time, immunodominance interferes with the development of a higher and broader immune response that could be able to completely eliminate the parasite. Based on this, we discuss how we can interfere with or take advantage of immunodominance in order to provide an immunotherapeutic alternative for chagasic individuals.

The Schedule for Nonadaptive and Adaptive Personality for Youth (SNAP-Y): a new measure for assessing adolescent personality and personality pathology.

PubMed

Linde, Jennifer A; Stringer, Deborah; Simms, Leonard J; Clark, Lee Anna

2013-08-01

The Schedule for Nonadaptive and Adaptive Personality-Youth Version (SNAP-Y) is a new, reliable self-report questionnaire that assesses 15 personality traits relevant to both normal-range personality and the alternative DSM-5 model for personality disorder. Community adolescents, 12 to 18 years old (N = 364), completed the SNAP-Y; 347 also completed the Big Five Inventory-Adolescent, 144 provided 2-week retest data, and 128 others completed the Minnesota Multiphasic Personality Inventory-Adolescent. Outpatient adolescents (N = 103) completed the SNAP-Y, and 97 also completed the Minnesota Multiphasic Personality Inventory-Adolescent. The SNAP-Y demonstrated strong psychometric properties, and structural, convergent, discriminant, and external validities. Consistent with the continuity of personality, results paralleled those in adult and college samples using the adult Schedule for Nonadaptive and Adaptive Personality-Second Edition (SNAP-2), from which the SNAP-Y derives and which has established validity in personality-trait assessment across the normal-abnormal continuum. The SNAP-Y thus provides a new, clinically useful instrument to assess personality traits and personality pathology in adolescents.

Behaviour, physiology and experience of pathological laughing and crying in amyotrophic lateral sclerosis.

PubMed

Olney, Nicholas T; Goodkind, Madeleine S; Lomen-Hoerth, Catherine; Whalen, Patrick K; Williamson, Craig A; Holley, Deborah E; Verstaen, Alice; Brown, Laurel M; Miller, Bruce L; Kornak, John; Levenson, Robert W; Rosen, Howard J

2011-12-01

Pathological laughing and crying is a disorder of emotional expression seen in a number of neurological diseases. The aetiology is poorly understood, but clinical descriptions suggest a disorder of emotion regulation. The goals of this study were: (i) to characterize the subjective, behavioural and physiological emotional reactions that occur during episodes of pathological laughing and crying; (ii) to compare responses during these episodes to those that occur when emotions are elicited under standard conditions (watching sad and amusing emotional films, being startled); and (iii) to examine the ability of patients with this disorder to regulate their emotions under standardized conditions. Twenty-one patients with pathological laughing and crying due to amyotrophic lateral sclerosis and 14 with amyotrophic lateral sclerosis but no pathological laughing and crying were studied. Emotional measures included self-reported emotional experience, video recordings of facial reactivity and peripheral physiological responses (skin conductance, heart rate and somatic activity). Nineteen of the 21 patients with histories of pathological laughing and crying had at least one episode in the laboratory that they agreed constituted pathological laughing or crying (a total of 56 episodes were documented). Compared with viewing sad and amusing films, the episodes were associated with greater facial and physiological activation. Contrary to many clinical descriptions, episodes were often induced by contextually appropriate stimuli and associated with strong experiences of emotion that were consistent with the display. When instructed to regulate their facial responses to emotion-eliciting films, patients with pathological laughing and crying showed impairments compared with patients who did not have a history of this disorder. These findings support the idea that pathological laughing and crying represents activation of all channels of emotional responding (i.e. behavioural, physiological and subjective). Furthermore, they support previously advanced theories that, rather than being associated with general emotional hyperreactivity, this disorder may be due to dysfunction in frontal neural systems that support voluntary regulation of emotion.

Behaviour, physiology and experience of pathological laughing and crying in amyotrophic lateral sclerosis

PubMed Central

Olney, Nicholas T.; Goodkind, Madeleine S.; Lomen-Hoerth, Catherine; Whalen, Patrick K.; Williamson, Craig A.; Holley, Deborah E.; Verstaen, Alice; Brown, Laurel M.; Miller, Bruce L.; Kornak, John; Levenson, Robert W.

2011-01-01

Pathological laughing and crying is a disorder of emotional expression seen in a number of neurological diseases. The aetiology is poorly understood, but clinical descriptions suggest a disorder of emotion regulation. The goals of this study were: (i) to characterize the subjective, behavioural and physiological emotional reactions that occur during episodes of pathological laughing and crying; (ii) to compare responses during these episodes to those that occur when emotions are elicited under standard conditions (watching sad and amusing emotional films, being startled); and (iii) to examine the ability of patients with this disorder to regulate their emotions under standardized conditions. Twenty-one patients with pathological laughing and crying due to amyotrophic lateral sclerosis and 14 with amyotrophic lateral sclerosis but no pathological laughing and crying were studied. Emotional measures included self-reported emotional experience, video recordings of facial reactivity and peripheral physiological responses (skin conductance, heart rate and somatic activity). Nineteen of the 21 patients with histories of pathological laughing and crying had at least one episode in the laboratory that they agreed constituted pathological laughing or crying (a total of 56 episodes were documented). Compared with viewing sad and amusing films, the episodes were associated with greater facial and physiological activation. Contrary to many clinical descriptions, episodes were often induced by contextually appropriate stimuli and associated with strong experiences of emotion that were consistent with the display. When instructed to regulate their facial responses to emotion-eliciting films, patients with pathological laughing and crying showed impairments compared with patients who did not have a history of this disorder. These findings support the idea that pathological laughing and crying represents activation of all channels of emotional responding (i.e. behavioural, physiological and subjective). Furthermore, they support previously advanced theories that, rather than being associated with general emotional hyperreactivity, this disorder may be due to dysfunction in frontal neural systems that support voluntary regulation of emotion. PMID:22155983

Evaluation of Response to Preoperative Chemotherapy Versus Surgery Alone in Gastroesophageal Cancer: Tumor Resectability, Pathologic Results and Post-Operative Complications.

PubMed

Kashefi Marandi, Aref; Shojaiefard, Abolfazl; Soroush, Ahmadreza; Ghorbani Abdegah, Ali; Jafari, Mehdi; Khodadost, Mahmoud; Mahmoudzade, Hossein

2016-01-01

Gastroesophageal cancer is one of the most common types of cancer worldwide. Despite significant developments in management, 5-year survival in the developing world is less than 20 percent. Due to restricted research about the impact of preoperative chemotherapy (POC) on tumor resection, pathological response and postoperative complications in Iran, we designed and implemented ‎the present retrospective cross- sectional study on 156 patients with gastroesophageal cancer (GEc) between 2013 and 2015 at Shariati Hospital of Tehran. Two groups were included, the first group had previously received preoperative chemotherapy and the second group had only undergone surgery. All patients were followed for at least one year after the operation in terms of tumor recurrence, relapse free survival and one-year survival. The two groups were eventually compared regarding tumor resection, pathological response, postoperative complications, recurrence rate and survival. The mean age was 66.5± 7.3 years and 78 percent were male. The tumor resectability, pathological response and postoperative complications in the group which received POC were 93.5%, 21.8% and 12.8%, respectively, and in the surgery alone group figures for tumor resection and postoperative complications were 76% and 29.5%, respectively. Also based on our study the 5-year survival in the POC group was better (79.5% vs. 66.5%). Using standard neoadjuvant regimens (preoperative chemotherapy/ chemoradiotherapy) beforesurgery could increase tumor resectability, pathological response, and improve the general status of the patients. Therefore using POC may be recommended over surgery alone.

Impact of extra-articular pathologies on groin pain: An arthroscopic evaluation.

PubMed

Kaya, Mitsunori

2018-01-01

For patients who have anterior hip pain evaluated by Patrick's test and tenderness at Scarpa's triangle, we perform periarticular debridement based on the hypothesis that extra-articular pathologies are responsible for the hip pain. The purpose of this study was to categorize the endoscopic extra-articular findings and to evaluate the clinical significance of periarticular pathologies in anterior hip pain. Arthroscopic findings of 77 patients who underwent periarthritic debridement were evaluated. As extra-articular pathologies, injuries of the direct head and reflective head of the rectus femoris muscle were evaluated. A thin layer of fat tissue normally exists on the anterior inferior iliac spine (AIIS), the attachment site of the direct head of the rectus femoris muscle. The macroscopic appearance of the fat pad on the AIIS was categorized as normal, blood vessel-rich adipose tissue or adipose tissue with fibrosis or scar formation and histologically confirmed. Adhesion of gluteal muscles to the joint capsule was also evaluated. Of the 77 patients, 75 had rupture of the direct head of the rectus femoris. In contrast, rupture of the reflective head was extremely rare. Seven patients had a normal fat pad on the AIIS, 11 had blood vessel-rich adipose tissue and 55 had adipose tissue with fibrosis. Fat tissue was completely replaced by fibrous scar tissue in another 4 patients. In 64 patients, adhesion between the anterior joint capsule and gluteus muscles was marked. Groin pain disappeared soon after the operation even when labral tears were not repaired and all patients returned to daily life and sports activities within 2 weeks after operation. Rectus femoris tendinosis, fibrosis of the AIIS fat pad, and adhesion of gluteal and rectus femoris muscles are common extra-articular pathologies in patients with anterior hip pain. Management of only these lesions induces rapid relief of anterior hip pain even in the absence of labral tear repair. My observations suggest that it is desirable to be aware of the presence of periarticular pathologies as a cause of groin pain.

Conductive hearing loss and middle ear pathology in young infants referred through a newborn universal hearing screening program in Australia.

PubMed

Aithal, Sreedevi; Aithal, Venkatesh; Kei, Joseph; Driscoll, Carlie

2012-10-01

Although newborn hearing screening programs have been introduced in most states in Australia, the prevalence of conductive hearing loss and middle ear pathology in the infants referred through these programs is not known. This study was designed to (1) evaluate the prevalence of conductive hearing loss and middle ear pathology in infants referred by a newborn hearing screening program in north Queensland, (2) compare prevalence rates of conductive hearing loss and middle ear pathology in indigenous and nonindigenous infants, and (3) review the outcomes of those infants diagnosed with conductive hearing loss and middle ear pathology. Retrospective chart review of infants referred to the Audiology Department of The Townsville Hospital was conducted. Chart review of 234 infants referred for one or both ears from a newborn hearing screening program in north Queensland was conducted. A total of 211 infants attended the diagnostic appointment. Review appointments to monitor hearing status were completed for 46 infants with middle ear pathology or conductive hearing loss. Diagnosis of hearing impairment was made using an age-appropriate battery of audiological tests. Results were analyzed for both initial and review appointments. Mean age at initial diagnostic assessment was 47.5 days (SD = 31.3). Of the 69 infants with middle ear pathology during initial diagnostic assessment, 18 had middle ear pathology with normal hearing, 47 had conductive hearing loss, and 4 had mixed hearing loss. Prevalence of conductive hearing loss in the newborns was 2.97 per 1,000 while prevalence of middle ear pathology (with or without conductive hearing loss) was 4.36 per 1,000. Indigenous Australians or Aboriginal and Torres Strait Islander (ATSI) infants had a significantly higher prevalence of conductive hearing loss and middle ear pathology than non-ATSI infants (35.19 and 44.45% vs 17.83 and 28.66%, respectively). ATSI infants also showed poor resolution of conductive hearing loss over time with 66.67% of ATSI infants reviewed showing persistent conductive hearing loss compared to 17.86% of non-ATSI infants. Medical management of 17 infants with persistent conductive hearing loss included monitoring, antibiotic treatment, examination under anesthesia, and grommet insertion. Conductive hearing loss was found to be a common diagnosis among infants referred through screening. ATSI infants had significantly higher rates of middle ear pathology and conductive hearing loss at birth and showed poor resolution of middle ear pathology over time compared to non-ATSI infants. Future research using a direct measure of middle ear function as an adjunct to the automated auditory brainstem response screening tool to distinguish conductive from sensorineural hearing loss may facilitate prioritization of infants for assessment, thus reducing parental anxiety and streamlining the management strategies for the respective types of hearing loss. American Academy of Audiology.

Pathological Narcissism and Interpersonal Behavior in Daily Life

PubMed Central

Roche, Michael J.; Pincus, Aaron L.; Conroy, David E.; Hyde, Amanda L.; Ram, Nilam

2014-01-01

The Cognitive-Affective Processing System (CAPS) has been proposed as a useful meta-framework for integrating contextual differences in situations with individual differences in personality pathology. In this article, we evaluated the potential of combining the CAPS meta-framework and contemporary interpersonal theory to investigate how individual differences in pathological narcissism influenced interpersonal functioning in daily life. University students (N = 184) completed event-contingent reports about interpersonal interactions across a 7-day diary study. Using multilevel regression models, we found that combinations of narcissistic expression (grandiosity, vulnerability) were associated with different interpersonal behavior patterns reflective of interpersonal dysfunction. These results are among the first to empirically demonstrate the usefulness of the CAPS model to conceptualize personality pathology through the patterning of if-then interpersonal processes. PMID:23205698

Do schema processes mediate links between parenting and eating pathology?

PubMed

Sheffield, Alex; Waller, Glenn; Emanuelli, Francesca; Murray, James; Meyer, Caroline

2009-07-01

Adverse parenting experiences are commonly linked to eating pathology. A schema-based model of the development and maintenance of eating pathology proposes that one of the potential mediators of the link between parenting and eating pathology might be the development of schema maintenance processes--mechanisms that operate to help the individual avoid intolerable emotions. To test this hypothesis, 353 female students and 124 female eating-disordered clients were recruited. They completed a measure of perceived parenting experiences as related to schema development (Young Parenting Inventory-Revised (YPI-R)), two measures of schema processes (Young Compensatory Inventory; Young-Rygh Avoidance Inventory (YRAI)) and a measure of eating pathology (Eating Disorders Inventory (EDI)). In support of the hypothesis, certain schema processes did mediate the relationship between specific perceptions of parenting and particular forms of eating pathology, although these were different for the clinical and non-clinical samples. In those patients where parenting is implicated in the development of eating pathology, treatment might need to target the cognitive processes that can explain this link. 2009 John Wiley & Sons, Ltd and Eating Disorders Association

Acculturative Stress, Self-Esteem, and Eating Pathology in Latina and Asian American Female College Students.

PubMed

Claudat, Kimberly; White, Emily K; Warren, Cortney S

2016-01-01

The overarching purpose of this study was to explore the relationships among acculturative stress, self-esteem, and eating pathology in Asian American and Latina female college students. Participants (N = 638, mean age = 19.88) completed self-report measures of the variables of interest online. Bivariate correlations indicated that for women of both ethnic groups, acculturative stress was negatively correlated with self-esteem and positively correlated with eating pathology. Multigroup structural equation modeling indicated that for Asian American and Latina women, self-esteem partially mediated the relationship between acculturative stress and eating pathology. However, self-esteem did not serve as a significant moderator of this relationship for either ethnic group. Overall, data suggest that acculturative stress is associated with increased eating pathology and self-esteem may mediate this relationship. These relationships suggest that assessment of eating pathology and self-esteem may be indicated for women presenting clinically with acculturative stress concerns. © 2015 Wiley Periodicals, Inc.

Deficits in oculomotor performance in pediatric epilepsy

PubMed Central

Asato, Miya R.; Nawarawong, Natalie; Hermann, Bruce; Crumrine, Patricia; Luna, Beatriz

2010-01-01

Summary Purpose Given evidence of limitations in neuropsychological performance in epilepsy, we probed the integrity of components of cognition, including speed of processing, response inhibition, and spatial working memory supporting executive function in pediatric epilepsy patients and matched controls. Methods A total of 44 pairs of controls and medically treated pediatric epilepsy patients with no known brain pathology completed cognitive oculomotor tasks, computerized neuropsychological testing, and psychiatric assessment. Results Patients showed slower reaction time to initiate a saccadic response compared to controls but had intact saccade accuracy. Cognitively driven responses including response inhibition were impaired in the patient group. Patients had increased incidence of comorbid psychopathology but comorbidity did not predict worse functioning compared to patients with no ADHD. Epilepsy type and medication status were not predictive of outcome. More complex neuropsychological performance was impaired in tasks requiring visual memory and sequential processing which was correlated with inhibitory control and antisaccade accuracy. Discussion Pediatric epilepsy may be associated with vulnerabilities that specifically undermine speed of processing and response inhibition but not working memory and may underlie known neuropsychological performance limitations. This particular profile of abnormalities may be associated with seizure-mediated compromises in brain maturation early in development. PMID:21087246

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

Igidbashian, Levon, E-mail: levonig@hotmail.co; Fortin, Bernard; Guertin, Louis

Purpose: To evaluate the role of neck dissection (ND) after chemoradiation therapy (CRT) for head and neck squamous cell carcinoma (HNSCC) with N3 disease. Methods and Materials: From March 1998 to September 2006, 70 patients with HNSCC and N3 neck disease were treated with concomitant CRT as primary therapy. Response to treatment was assessed using clinical examination and computed tomography 6 to 8 weeks posttreatment. Neck dissection was not routinely performed and considered for those with less than complete response. Of the patients, 26 (37.1%) achieved clinical complete response (cCR) after CRT. A total of 31 (44.3%) underwent ND aftermore » partial response (cPR-ND). Thirteen patients (29.5%) did not achieve cCR and did not undergo ND for the following reasons: incomplete response/progression at primary site, refusal/contraindication to surgery, metastatic progression, or death. These patients were excluded from the analysis. Outcomes were computed using Kaplan-Meier curves and were compared with log rank tests. Results: Comparing the cCR and cPR-ND groups at 2 years, the disease-free survival was respectively 62.7% and 84.9% (p = 0.048); overall survival was 63.0% and 79.4% (p = 0.26), regional relapse-free survival was 87.8% and 96.0% (p = 0.21); and distant disease-free survival was 67.1% and 92.6% (p = 0.059). In the cPR-ND group, 71.0% had no pathologic evidence of disease (PPV of 29.0%). Conclusions: Patients with N3 disease achieving regional cPR and primary cCR who underwent ND seemed to have better outcomes than patients achieving global cCR without ND. Clinical assessment with computed tomography is not adequate for evaluating response to treatment. Because of the inherent limitations of our study, further confirmatory studies are warranted.« less

Emergency Surgery for Refractory Status Epilepticus.

PubMed

Botre, Abhijeet; Udani, Vrajesh; Desai, Neelu; Jagadish, Spoorthy; Sankhe, Milind

2017-08-15

Management of refractory status epilepticus in children is extremely challenging. Two children with medically refractory status epilepticus, both of whom had lesional pathology on MRI and concordant data on EEG and PET scan. Emergency hemispherotomy performed in both patients. A complete, sustained seizure freedom obtained postoperatively. Emergency surgery is a treatment option in selected cases of drug refractory status epilepticus with lesional pathology and concordant data.

The accuracy of echocardiography versus surgical and pathological classification of patients with ruptured mitral chordae tendineae: a large study in a Chinese cardiovascular center

PubMed Central

2011-01-01

Background The accuracy of echocardiography versus surgical and pathological classification of patients with ruptured mitral chordae tendineae (RMCT) has not yet been investigated with a large study. Methods Clinical, hemodynamic, surgical, and pathological findings were reviewed for 242 patients with a preoperative diagnosis of RMCT that required mitral valvular surgery. Subjects were consecutive in-patients at Fuwai Hospital in 2002-2008. Patients were evaluated by thoracic echocardiography (TTE) and transesophageal echocardiography (TEE). RMCT cases were classified by location as anterior or posterior, and classified by degree as partial or complete RMCT, according to surgical findings. RMCT cases were also classified by pathology into four groups: myxomatous degeneration, chronic rheumatic valvulitis (CRV), infective endocarditis and others. Results Echocardiography showed that most patients had a flail mitral valve, moderate to severe mitral regurgitation, a dilated heart chamber, mild to moderate pulmonary artery hypertension and good heart function. The diagnostic accuracy for RMCT was 96.7% for TTE and 100% for TEE compared with surgical findings. Preliminary experiments demonstrated that the sensitivity and specificity of diagnosing anterior, posterior and partial RMCT were high, but the sensitivity of diagnosing complete RMCT was low. Surgical procedures for RMCT depended on the location of ruptured chordae tendineae, with no relationship between surgical procedure and complete or partial RMCT. The echocardiographic characteristics of RMCT included valvular thickening, extended subvalvular chordae, echo enhancement, abnormal echo or vegetation, combined with aortic valve damage in the four groups classified by pathology. The incidence of extended subvalvular chordae in the myxomatous group was higher than that in the other groups, and valve thickening in combination with AV damage in the CRV group was higher than that in the other groups. Infective endocarditis patients were younger than those in the other groups. Furthermore, compared other groups, the CRV group had a larger left atrium, higher aortic velocity, and a higher pulmonary arterial systolic pressure. Conclusions Echocardiography is a reliable method for diagnosing RMCT and is useful for classification. Echocardiography can be used to guide surgical procedures and for preliminary determination of RMCT pathological types. PMID:21801375

The effect of obesity on pathological complete response and survival in breast cancer patients receiving uncapped doses of neoadjuvant anthracycline-taxane-based chemotherapy.

PubMed

Farr, Alex; Stolz, Myriam; Baumann, Lukas; Bago-Horvath, Zsuzsanna; Oppolzer, Elisabeth; Pfeiler, Georg; Seifert, Michael; Singer, Christian F

2017-06-01

The effect of obesity in breast cancer patients undergoing neoadjuvant chemotherapy (NAC) remains controversial. The aim of this study was to determine the obesity-related effect on pathological complete response (pCR) and survival in women receiving full uncapped doses of NAC. We retrospectively analyzed the data of all consecutive women who underwent anthracycline-taxane-based NAC for primary breast cancer between 2005 and 2015 at the Department of Obstetrics and Gynecology, Medical University of Vienna. Following the WHO criteria, women with a body mass index (BMI) ≥30 kg/m 2 at baseline were considered obese, whereas those with a BMI <30 kg/m 2 were considered non-obese. Those with dose reductions or dose capping were not eligible for study inclusion. Cox regression and logistic regression were performed. The Kaplan-Meier method was used to analyze disease-free, progression-free, and overall survival. The pCR served as the main outcome measure. Among 120 women who received neoadjuvant epirubicin plus cyclophosphamide and docetaxel, 28 (23.3%) were obese and 92 (76.7%) were non-obese. In the multivariate logistic regression model that adjusted for potentially confounding variables, obesity had an independent positive predictive effect on pCR (OR 4.29, 95% CI, 1.42-13.91; p = 0.011), which was significant in the postmenopausal subgroup (OR 4.72, 95% CI, 1.47-15.84; p = 0.01). When comparing non-obese with obese women, we found that obese women experienced longer progression-free survival (HR 0.10, 95% CI, 8.448 × 10 -4 -0.81; p = 0.025). Obese women receiving full uncapped doses of anthracycline-taxane-based NAC have increased pCR and favorable progression-free survival. This could result from increased dose intensity with increased efficacy and toxicity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Tumour size is the only predictive factor of distant recurrence after pathological complete response to neoadjuvant chemotherapy in patients with large operable or locally advanced breast cancers: a sub-study of EORTC 10994/BIG 1-00 phase III trial.

PubMed

Fei, F; Messina, C; Slaets, L; Chakiba, C; Cameron, D; Bogaerts, J; Bonnefoi, H

2015-02-01

Although achieving a pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) in breast cancer predicts a better outcome, some patients still relapse. The objectives of this study were to describe the types of events in this group of patients and to identify predictive factors for relapse. Patients with large operable or locally advanced breast cancers (T4d tumours were excluded) were randomised to receive either six cycles of anthracycline-based chemotherapy or three cycles of docetaxel followed by three cycles of eprirubicin/docetaxel. pCR was defined as no evidence of residual invasive cancer (or very few scattered tumour cells) in the primary tumour and axillary lymph nodes at surgery. Two Cox regression analyses were performed to identify predictive factors of relapse: one for recurrence-free interval (RFI) and one for distant recurrence-free interval (DRFI). Out of 283 eligible patients who achieved a pCR, 40 (14.1%) and 28 (9.9%) presented an event of interest for the RFI and DRFI analyses, respectively. Five-year RFI, DRFI and overall survival (OS) were 85.3% (95% confidence interval (CI), 80.1-89.3), 89.6% (95% CI, 85.0-92.9) and 91.9% (95% CI, 87.2-94.9), respectively. No predictors for RFI after pCR were identified. For DRFI, tumour size was the only predictor: Hazard ratio (HR) T3 versus T1-2=3.62 (95% CI, 1.66-7.89); HR T4 versus T1-2: HR, 2.80 (95% CI, 0.62-12.64) p=0.0048. In this study, clinical tumour size emerged as the only predictor for DRFI after pCR, with T3 and T4 tumours having an increased risk for distant recurrence compared to T1-2 tumours. Copyright © 2014 Elsevier Ltd. All rights reserved.

Pathologic complete response and disease-free survival are not surrogate endpoints for 5-year survival in rectal cancer: an analysis of 22 randomized trials.

PubMed

Petrelli, Fausto; Borgonovo, Karen; Cabiddu, Mary; Ghilardi, Mara; Lonati, Veronica; Barni, Sandro

2017-02-01

We performed a literature-based analysis of randomized clinical trials to assess the pathologic complete response (pCR) (ypT0N0 after neoadjuvant therapy) and 3-year disease-free survival (DFS) as potential surrogate endpoints for 5-year overall survival (OS) in rectal cancer treated with neoadjuvant (chemo)radiotherapy (CT)RT. A systematic literature search of PubMed, EMBASE, the Web of Science, SCOPUS, CINAHL, and the Cochrane Library was performed. Treatment effects on 3-year DFS and 5-year OS were expressed as rates of patients alive (%), and those on pCR as differences in pCR rates (∆ pCR% ). A weighted regression analysis was performed at individual- and trial-level to test the association between treatment effects on surrogate (∆ pCR% and ∆ 3yDFS ) and the main clinical outcome (∆ 5yOS ). Twenty-two trials involving 10,050 patients, were included in the analysis. The individual level surrogacy showed that the pCR% and 3-year DFS were poorly correlated with 5-year OS (R=0.52; 95% CI, 0.31-0.91; P=0.002; and R=0.60; 95% CI, 0.36-1; P=0.002). The trial-level surrogacy analysis confirmed that the two treatment effects on surrogates (∆ pCR% and ∆ 3yDFS ) are not strong surrogates for treatment effects on 5-year OS % (R=0.2; 95% CI, -0.29-0.78; P=0.5 and R=0.64; 95% CI, 0.29-1; P=0.06). These findings were confirmed in neoadjuvant CTRT studies but not in phase III trials were 3-year DFS could still represent a valid surrogate. This analysis does not support the use of pCR and 3-year DFS% as appropriate surrogate endpoints for 5-year OS% in patients with rectal cancer treated with neoadjuvant therapy.

Value of FDG-PET/CT Volumetry After Chemoradiotherapy in Rectal Cancer.

PubMed

Okuno, Takayuki; Kawai, Kazushige; Koyama, Keitaro; Takahashi, Miwako; Ishihara, Soichiro; Momose, Toshimitsu; Morikawa, Teppei; Fukayama, Masashi; Watanabe, Toshiaki

2018-03-01

Neoadjuvant chemoradiotherapy followed by an optimal surgery is the standard treatment for patients with locally advanced rectal cancer. FDG-PET/CT is commonly used as the modality for assessing the effect of chemoradiotherapy. The purpose of this study was to investigate whether PET/CT-based volumetry could contribute to the prediction of pathological complete response or prognosis after neoadjuvant chemoradiotherapy. This was a retrospective cohort study. This study was conducted at a single research center. Ninety-one consecutive patients with locally advanced rectal cancer were enrolled between January 2005 and December 2015. Patients underwent PET/CT before and after neoadjuvant chemoradiotherapy. Maximum standardized uptake value and total lesion glycolysis on PET/CT before and after neoadjuvant chemoradiotherapy were calculated using isocontour methods. Correlations between these variables and clinicopathological factors and prognosis were assessed. PET/CT-associated variables before chemoradiotherapy were not correlated with either clinicopathological factors or prognosis. Maximum standardized uptake value was associated with pathological complete response, but total lesion glycolysis was not. Maximum standardized uptake value correlated with ypT, whereas total lesion glycolysis correlated with both ypT and ypN. High total lesion glycolysis was associated with a considerably poorer prognosis; the 5-year recurrence rate was 65% and the 5-year mortality rate 42%, whereas in lesions with low total lesion glycolysis, these were 6% and 2%. On multivariate analysis, high total lesion glycolysis was an independent risk factor for recurrence (HR = 4.718; p = 0.04). The gain in fluoro-2-deoxy-D-glucose uptake may differ between scanners, thus the general applicability of this threshold should be validated. In patients with locally advanced rectal cancer, high total lesion glycolysis after neoadjuvant chemoradiotherapy is strongly associated with a worse prognosis. Total lesion glycolysis after chemoradiotherapy may be a promising preoperative predictor of recurrence and death. See Video Abstract at http://links.lww.com/DCR/A464.

Proton therapy posterior beam approach with pencil beam scanning for esophageal cancer : Clinical outcome, dosimetry, and feasibility.

PubMed

Zeng, Yue-Can; Vyas, Shilpa; Dang, Quang; Schultz, Lindsay; Bowen, Stephen R; Shankaran, Veena; Farjah, Farhood; Oelschlager, Brant K; Apisarnthanarax, Smith; Zeng, Jing

2016-12-01

The aim of this study is to present the dosimetry, feasibility, and preliminary clinical results of a novel pencil beam scanning (PBS) posterior beam technique of proton treatment for esophageal cancer in the setting of trimodality therapy. From February 2014 to June 2015, 13 patients with locally advanced esophageal cancer (T3-4N0-2M0; 11 adenocarcinoma, 2 squamous cell carcinoma) were treated with trimodality therapy (neoadjuvant chemoradiation followed by esophagectomy). Eight patients were treated with uniform scanning (US) and 5 patients were treated with a single posterior-anterior (PA) beam PBS technique with volumetric rescanning for motion mitigation. Comparison planning with PBS was performed using three plans: AP/PA beam arrangement; PA plus left posterior oblique (LPO) beams, and a single PA beam. Patient outcomes, including pathologic response and toxicity, were evaluated. All 13 patients completed chemoradiation to 50.4 Gy (relative biological effectiveness, RBE) and 12 patients underwent surgery. All 12 surgical patients had an R0 resection and pathologic complete response was seen in 25 %. Compared with AP/PA plans, PA plans have a lower mean heart (14.10 vs. 24.49 Gy, P < 0.01), mean stomach (22.95 vs. 31.33 Gy, P = 0.038), and mean liver dose (3.79 vs. 5.75 Gy, P = 0.004). Compared to the PA/LPO plan, the PA plan reduced the lung dose: mean lung dose (4.96 vs. 7.15 Gy, P = 0.020) and percentage volume of lung receiving 20 Gy (V 20 ; 10 vs. 17 %, P < 0.01). Proton therapy with a single PA beam PBS technique for preoperative treatment of esophageal cancer appears safe and feasible.

The Effect of Mental Rotation on Surgical Pathological Diagnosis.

PubMed

Park, Heejung; Kim, Hyun Soo; Cha, Yoon Jin; Choi, Junjeong; Minn, Yangki; Kim, Kyung Sik; Kim, Se Hoon

2018-05-01

Pathological diagnosis involves very delicate and complex consequent processing that is conducted by a pathologist. The recognition of false patterns might be an important cause of misdiagnosis in the field of surgical pathology. In this study, we evaluated the influence of visual and cognitive bias in surgical pathologic diagnosis, focusing on the influence of "mental rotation." We designed three sets of the same images of uterine cervix biopsied specimens (original, left to right mirror images, and 180-degree rotated images), and recruited 32 pathologists to diagnose the 3 set items individually. First, the items found to be adequate for analysis by classical test theory, Generalizability theory, and item response theory. The results showed statistically no differences in difficulty, discrimination indices, and response duration time between the image sets. Mental rotation did not influence the pathologists' diagnosis in practice. Interestingly, outliers were more frequent in rotated image sets, suggesting that the mental rotation process may influence the pathological diagnoses of a few individual pathologists. © Copyright: Yonsei University College of Medicine 2018.

Interpersonal perception of pathological narcissism: a social relations analysis.

PubMed

Lukowitsky, Mark R; Pincus, Aaron L

2013-01-01

Impairments in self and interpersonal functioning are core features of personality pathology. Clinical theory and research indicate that compromised self-awareness and distorted interpersonal perceptions are particularly prominent in individuals exhibiting pathological narcissism and Narcissistic Personality Disorder. Therefore we conducted a study to gain a better understanding of interpersonal perception of pathological narcissism. A large sample (N=437) of moderately acquainted individuals assigned to 1 of 93 small mixed-sex groups completed self- and informant ratings on the Pathological Narcissism Inventory (PNI) in a round-robin design. The social relations model (SRM) was used to partition the variance in dyadic ratings to investigate several hypotheses about interpersonal perception of pathological narcissism. SRM analyses demonstrated evidence of assimilation (the tendency to perceive and rate others similarly) and consensus (the extent to which multiple observers form similar impressions of another person) in interpersonal perception of pathological narcissism. Results also indicated modest self-other agreement and assumed similarity (the tendency for people to perceive others as similar to themselves) for PNI higher order factors and subscale ratings. Finally, results suggested that individuals high in pathological narcissism had some awareness of how peers would rate them (metaperception) but believed that others would rate them similarly to how they rated themselves.

Rumination mediates the relationship between peer alienation and eating pathology in young adolescent girls.

PubMed

Hilt, Lori M; Roberto, Christina A; Nolen-Hoeksema, Susan

2013-09-01

This study examined whether rumination, the tendency to passively and repeatedly dwell on negative events, mediated the relationship between peer alienation and eating disorder symptoms among adolescent girls. Participants included 101 girls (ages 10-14; 47% Hispanic, 24% African American) who completed questionnaires regarding peer relationships, symptoms of eating pathology, rumination, and depressive symptoms. Girls who reported experiencing more peer alienation reported a higher degree of pathological eating symptoms. The relationship between peer alienation and eating pathology was mediated by rumination, even after controlling for depressive symptoms. This study extends previous work indicating that rumination is a cognitive mechanism that may contribute to the development and/or maintenance of eating pathology. The findings suggest that adolescents who feel alienated by their peers might be particularly susceptible to engaging in ruminative thinking that can lead to or exacerbate eating problems.

Serendipia: Castilla-La Mancha telepathology network

PubMed Central

Peces, Carlos; García-Rojo, Marcial; Sacristán, José; Gallardo, Antonio José; Rodríguez, Ambrosio

2008-01-01

Nowadays, there is no standard solution for acquiring, archiving and communication of Pathology digital images. In addition, there does not exist any commercial Pathology Information System (LIS) that can manage the relationship between the reports generated by the pathologist and their corresponding images. Due to this situation, the Healthcare Service of Castilla-La Mancha decided to create a completely digital Pathology Department, the project is called SERENDIPIA. SERENDIPIA project provides all the necessary image acquiring devices needed to cover all kind of images that can be generated in a Pathology Department. In addition, in the SERENDIPIA project an Information System was developed that allows, on the one hand, it to cover the daily workflow of a Pathology Department (including the storage and the manage of the reports and its images), and, on the other hand, the Information System provides a WEB telepathology portal with collaborative tools like second opinion. PMID:18673519

The impact of early symptom change and therapeutic alliance on treatment outcome in cognitive-behavioural therapy for eating disorders.

PubMed

Turner, Hannah; Bryant-Waugh, Rachel; Marshall, Emily

2015-10-01

The present study explored the impact of early symptom change (cognitive and behavioural) and the early therapeutic alliance on treatment outcome in cognitive-behavioural therapy (CBT) for the eating disorders. Participants were 94 adults with diagnosed eating disorders who completed a course of CBT in an out-patient community eating disorders service in the UK. Patients completed a measure of eating disorder psychopathology at the start of treatment, following the 6th session and at the end of treatment. They also completed a measure of therapeutic alliance following the 6th session. Greater early reduction in dietary restraint and eating concerns, and smaller levels of change in shape concern, significantly predicted later reduction in global eating pathology. The early therapeutic alliance was strong across the three domains of tasks, goals and bond. Early symptom reduction was a stronger predictor of later reduction in eating pathology than early therapeutic alliance. The early therapeutic alliance did not mediate the relationship between early symptom reduction and later reduction in global eating pathology. Instead, greater early symptom reduction predicted a strong early therapeutic alliance. Early clinical change was the strongest predictor of treatment outcome and this also facilitated the development of a strong early alliance. Clinicians should be encouraged to deliver all aspects of evidence-based CBT, including behavioural change. The findings suggest that this will have a positive impact on both the early therapeutic alliance and later change in eating pathology. Copyright © 2015 Elsevier Ltd. All rights reserved.

Next Generation Quality: Assessing the Physician in Clinical History Completeness and Diagnostic Interpretations Using Funnel Plots and Normalized Deviations Plots in 3,854 Prostate Biopsies.

PubMed

Bonert, Michael; El-Shinnawy, Ihab; Carvalho, Michael; Williams, Phillip; Salama, Samih; Tang, Damu; Kapoor, Anil

2017-01-01

Observational data and funnel plots are routinely used outside of pathology to understand trends and improve performance. Extract diagnostic rate (DR) information from free text surgical pathology reports with synoptic elements and assess whether inter-rater variation and clinical history completeness information useful for continuous quality improvement (CQI) can be obtained. All in-house prostate biopsies in a 6-year period at two large teaching hospitals were extracted and then diagnostically categorized using string matching, fuzzy string matching, and hierarchical pruning. DRs were then stratified by the submitting physicians and pathologists. Funnel plots were created to assess for diagnostic bias. 3,854 prostate biopsies were found and all could be diagnostically classified. Two audits involving the review of 700 reports and a comparison of the synoptic elements with the free text interpretations suggest a categorization error rate of <1%. Twenty-seven pathologists each read >40 cases and together assessed 3,690 biopsies. There was considerable inter-rater variability and a trend toward more World Health Organization/International Society of Urologic Pathology Grade 1 cancers in older pathologists. Normalized deviations plots, constructed using the median DR, and standard error can elucidate associated over- and under-calls for an individual pathologist in relation to their practice group. Clinical history completeness by submitting medical doctor varied significantly (100% to 22%). Free text data analyses have some limitations; however, they could be used for data-driven CQI in anatomical pathology, and could lead to the next generation in quality of care.

Progressive Primary Pulmonary Tuberculosis Presenting as the Sudden Unexpected Death in Infancy: A Case Report

PubMed Central

Dempers, Johan; Sens, Mary Ann; Wadee, Shabbir Ahmed; Kinney, Hannah C.; Odendaal, Hein J.; Wright, Colleen A.

2010-01-01

The classification of an unexpected infant death as the sudden infant death syndrome (SIDS) depends upon a complete autopsy and death scene investigation to exclude known causes of death. Here we report the death of a four-month-old infant in a tuberculosis endemic area that presented as a sudden unexpected death in infancy (SUDI) with no apparent explanation based on the death scene characteristics. The autopsy, however, revealed progressive primary pulmonary tuberculosis with intrathoracic adenopathy, compression of the tracheobronchial tree and miliary lesions in the liver. This case underscores the clinical difficulties in the diagnosis of infantile tuberculosis, as well as the possibility of sudden death as part of its protean manifestations. The pathology and clinical progression of tuberculosis in infants differs from older children and adults due to the immature immune response in infants. This case dramatically highlights the need for complete autopsies in all sudden and unexpected infant deaths, as well as the public health issues in a sentinel infant tuberculosis diagnosis. PMID:20705406

MRI Predictive Factors for Tumor Response in Rectal Cancer Following Neoadjuvant Chemoradiation Therapy - Implications for Induction Chemotherapy?

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

Yu, Stanley K.T.; Tait, Diana; Chau, Ian

2013-11-01

Purpose: Clinical and magnetic resonance imaging (MRI) characteristics at baseline and following chemoradiation therapy (CRT) most strongly associated with histopathologic response were investigated and survival outcomes evaluated in accordance with imaging and pathological response. Methods and Materials: Responders were defined as mrT3c/d-4 downstaged to ypT0-2 on pathology or low at risk mrT2 downstaged to ypT1 or T0. Multivariate logistic regression of baseline and posttreatment MRI: T, N, extramural venous invasion (EMVI), circumferential resection margin, craniocaudal length <5 cm, and MRI tumor height ≤5 cm were used to identify independent predictor(s) for response. An association between induction chemotherapy and EMVI statusmore » was analyzed. Survival outcomes for pathologic and MRI responders and nonresponders were analyzed. Results: Two hundred eighty-one patients were eligible; 114 (41%) patients were pathology responders. Baseline MRI negative EMVI (odds ratio 2.94, P=.007), tumor height ≤5 cm (OR 1.96, P=.02), and mrEMVI status change (positive to negative) following CRT (OR 3.09, P<.001) were the only predictors for response. There was a strong association detected between induction chemotherapy and ymrEMVI status change after CRT (OR 9.0, P<.003). ymrT0-2 gave a positive predictive value of 80% and OR of 9.1 for ypT0-2. ymrN stage accuracy of ypN stage was 75%. Three-year disease-free survival for pathology and MRI responders were similar at 80% and 79% and significantly better than poor responders. Conclusions: Tumor height and mrEMVI status are more important than baseline size and stage of the tumor as predictors of response to CRT. Both MRI- and pathologic-defined responders have significantly improved survival. “Good response” to CRT in locally advanced rectal cancer with ypT0-2 carries significantly better 3-year overall survival and disease-free survival. Use of induction chemotherapy for improving mrEMVI status and knowledge of MRI predictive factors could be taken into account in the pursuit of individualized neoadjuvant treatments for patients with rectal cancer.« less

Surgical excision of skin cancer: the importance of training.

PubMed

Salmon, P; Mortimer, N; Rademaker, M; Adams, L; Stanway, A; Hill, S

2010-01-01

Background Skin cancers are the most common malignancy in New Zealand and their treatment imparts a huge burden on the healthcare system both in terms of the cost of surgical intervention and in treatment delivery (estimates are in excess of NZ$33 million per annum for the year 2000). Currently in New Zealand, skin cancers are excised by dermatologists, general practitioners (GPs), GPs with a special interest in skin surgery (GPSIs) and specialist surgeons with diverse training backgrounds including ear, nose and throat, ophthalmic and general surgeons. To date there is scant literature evaluating complete excision rates following surgical treatment of skin cancer between these vocational groups. Objectives To review retrospectively pathology reports from all skin excisions sent to one private pathology laboratory over three consecutive months. The aim was to investigate the margins of excision and completeness of skin cancer surgery performed by each vocational group. Methods A retrospective analysis of skin pathology reports was undertaken for a 3-month period between April and June 2007. Raw data obtained from the pathology reports included diagnosis, completeness of excision, size of specimens, body site and vocational group of the medical practitioner performing the surgery. Results In total, 1532 lesions were excised: 432 benign and 1100 malignant. Six hundred and seven were from the head and neck. Dermatologists excised 276 lesions of which 93% were malignant, 55% were from the head and neck, and 0% were incompletely excised. GPs excised 633 lesions: 63% malignant, 30% head and neck, 23% incomplete excision of malignant lesions. GPSIs excised 368 lesions: 71% malignant, 35% head and neck, 21.5% incomplete malignant excision. Specialist surgeons excised 255 lesions: 72% malignant, 53% head and neck, 20% incomplete malignant excision. Conclusion GPs and GPSIs excised more benign lesions and had higher incomplete excision rates of skin cancer surgery than dermatologists. Incomplete excision rates for the vocational groups ranged from 0% to 45% depending on site and pathology.

Anatomy, pathology, and physiology of the tracheobronchial tree: emphasis on the distal airways.

PubMed

Hyde, Dallas M; Hamid, Qutayba; Irvin, Charles G

2009-12-01

This article covers the airway tree with respect to anatomy, pathology, and physiology. The anatomic portion discusses various primate groups so as to help investigators understand similarities and differences between animal models. An emphasis is on distal airway findings. The pathology section focuses on the inflammatory responses that occur in proximal and distal airways. The physiologic review brings together the anatomic and pathologic components to the functional state and proposes ways to evaluate the small airways in patients with asthma.

Pulmonary cryptococcosis in rheumatoid arthritis (RA) patients: comparison of imaging characteristics among RA, acquired immunodeficiency syndrome, and immunocompetent patients.

PubMed

Yanagawa, Noriyo; Sakai, Fumikazu; Takemura, Tamiko; Ishikawa, Satoru; Takaki, Yasunobu; Hishima, Tsunekazu; Kamata, Noriko

2013-11-01

The imaging characteristics of cryptococcosis in rheumatoid arthritis (RA) patients were analyzed by comparing them with those of acquired immunodeficiency syndrome (AIDS) and immunocompetent patients, and the imaging findings were correlated with pathological findings. Two radiologists retrospectively compared the computed tomographic (CT) findings of 35 episodes of pulmonary cryptococcosis in 31 patients with 3 kinds of underlying states (10 RA, 12 AIDS, 13 immunocompetent), focusing on the nature, number, and distribution of lesions. The pathological findings of 18 patients (8 RA, 2 AIDS, 8 immunocompetent) were analyzed by two pathologists, and then correlated with imaging findings. The frequencies of consolidation and ground glass attenuation (GGA) were significantly higher, and the frequency of peripheral distribution was significantly lower in the RA group than in the immunocompetent group. Peripheral distribution was less common and generalized distribution was more frequent in the RA group than in the AIDS group. The pathological findings of the AIDS and immunocompetent groups reflected their immune status: There was lack of a granuloma reaction in the AIDS group, and a complete granuloma reaction in the immunocompetent group, while the findings of the RA group varied, including a complete granuloma reaction, a loose granuloma reaction and a hyper-immune reaction. Cases with the last two pathologic findings were symptomatic and showed generalized or central distribution on CT. Cryptococcosis in the RA group showed characteristic radiological and pathological findings compared with the other 2 groups. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Pathology resident attitudes and opinions about pathologists' assistants.

PubMed

Grzybicki, Dana Marie; Vrbin, Colleen M

2003-06-01

Changes in health care economics and organization have resulted in increased use of nonphysician providers in most health care settings. Attitudinal acceptance of nonphysician providers is important in the current health care environment. To obtain descriptive information regarding pathology resident attitudes and opinions about pathologists' assistants in anatomic pathology practice and to assess the implications of resident attitudes and opinions for pathology practice and training. A self-administered, mailed, voluntary, anonymous questionnaire was distributed to a cross-sectional sample of pathology residents in the United States (2531 pathology residents registered as resident members of one of the national pathology professional organizations). The questionnaire contained (1) items relating to resident demographics and program characteristics, (2) Likert-scale response items containing positive and negative statements about pathologists' assistants, (3) a multiple-choice item related to pathologists' assistants scope of practice, and (4) an open-ended item inviting additional comments. Both quantitative and qualitative analysis of responses was performed. The overall response rate was 19.4% (n = 490); 50% of the respondents were women, and 77% reported use of pathologists' assistants in their program. Most respondents were 25 to 35 years old and in postgraduate years 3 through 5 of their training, and most were located in the Midwestern United States. The majority of residents expressed overall positive attitudes and opinions about pathologists' assistants and felt that pathologists' assistants enhanced resident training by optimizing resident workload. A minority (10%-20%) of residents expressed negative attitudes or opinions about pathologists' assistants. Additionally, some residents reported a lack of knowledge about pathologists' assistants' training or roles. Increased resident education and open discussion concerning pathologists' assistants may be beneficial for optimizing resident attitudes about and training experiences with pathologists' assistants.

The contribution of Chlamydia-specific CD8⁺ T cells to upper genital tract pathology.

PubMed

Vlcek, Kelly R; Li, Weidang; Manam, Srikanth; Zanotti, Brian; Nicholson, Bruce J; Ramsey, Kyle H; Murthy, Ashlesh K

2016-02-01

Genital chlamydial infections lead to severe upper reproductive tract pathology in a subset of untreated women. We demonstrated previously that tumor necrosis factor (TNF)-α-producing CD8(+) T cells contribute significantly to chlamydial upper genital tract pathology in female mice. In addition, we observed that minimal chlamydial oviduct pathology develops in OT-1 transgenic (OT-1) mice, wherein the CD8(+) T-cell repertoire is restricted to recognition of the ovalbumin peptide Ova(257-264), suggesting that non-Chlamydia-specific CD8(+) T cells may not be responsible for chlamydial pathogenesis. In the current study, we evaluated whether antigen-specific CD8(+) T cells mediate chlamydial pathology. Groups of wild-type (WT) C57BL/6J, OT-1 mice, and OT-1 mice replete with WT CD8(+) T cells (1 × 10(6) cells per mouse intravenously) were infected intravaginally with C. muridarum (5 × 10(4) IFU/mouse). Serum total anti-Chlamydia antibody and total splenic anti-Chlamydia interferon (IFN)-γ and TNF-α responses were comparable among the three groups of animals. However, Chlamydia-specific IFN-γ and TNF-α production from purified splenic CD8(+) T cells of OT-1 mice was minimal, whereas responses in OT-1 mice replete with WT CD8(+) T cells were comparable to those in WT animals. Vaginal chlamydial clearance was comparable between the three groups of mice. Importantly, the incidence and severity of oviduct and uterine horn pathology was significantly reduced in OT-1 mice but reverted to WT levels in OT-1 mice replete with WT CD8(+) T cells. Collectively, these results demonstrate that Chlamydia-specific CD8(+) T cells contribute significantly to upper genital tract pathology.

Treatment adherence and outcome in women with inflammatory breast cancer: does race matter?

PubMed

Andic, Fundagul; Godette, Karen; O'Regan, Ruth; Zelnak, Amelia; Liu, Tian; Rizzo, Monica; Gabram, Sheryl; Torres, Mylin

2011-12-15

The authors compared treatment adherence rates and outcome in Caucasian and African American patients with inflammatory breast cancer (IBC). The records of 55 (25 Caucasian and 30 African American) IBC patients treated with curative intent from 1995 to 2009 were reviewed. All patients received neoadjuvant doxorubicin (Adriamycin) and/or taxane-based chemotherapy, and mastectomy with or without radiotherapy. The median follow-up period for Caucasian and African American patients was similar (39.5 months and 36.1 months, respectively). There was no difference between races in median age, tumor size, grade, and receptor status at diagnosis. The number of patients who completed neoadjuvant chemotherapy, surgery, and radiotherapy did not differ by race (84% of Caucasians vs 86.7% of African Americans) nor did the median length of time to complete trimodality treatment (263 [range, 207-422] days for Caucasians vs 262 [range, 165-371] days for African Americans). There was a trend toward slightly higher pathological complete response rates in Caucasian than African American women (20% in Caucasians vs 6.7% in African Americans, P = .23). Despite slightly better response rates to neoadjuvant chemotherapy, Caucasian patients did not have higher 3-year local control rates (70% in Caucasians vs 64% in African Americans, P = .73). However, there was a trend toward higher 3-year overall survival in Caucasian versus African American patients (73% in Caucasians vs 55% in African Americans, P = .09) and higher distant metastasis-free survival (60% in Caucasians vs 40% in African Americans, P = .19). This study is among the largest to examine patients with IBC by race. Being Caucasian or African American did not appear to impact treatment adherence. However, African American patients tended to have poorer response to standard treatment and worse outcome than Caucasian patients. Copyright © 2011 American Cancer Society.

Neoadjuvant conformal chemoradiation with induction chemotherapy for rectal adenocarcinoma. A prospective observational study.

PubMed

Fekete, Zsolt; Muntean, Alina-Simona; Hica, Ştefan; Rancea, Alin; Resiga, Liliana; Csutak, Csaba; Todor, Nicolae; Nagy, Viorica Magdalena

2014-06-01

The purpose of this prospective observational study was to evaluate the rate and the prognostic factors for down-staging and complete response for rectal adenocarcinoma after induction chemotherapy and neoadjuvant chemoradiation followed by surgery, and to analyze the rate of sphincter-saving surgery. We included from March 2011 to October 2013 a number of 88 patients hospitalized with locally advanced rectal adenocarcinoma in the Prof. Dr. Ion Chiricuta Institute of Oncology, Cluj. The treatment schedule included 2-4 cycles of Oxaliplatin plus a fluoropyrimidine followed by concomitant chemoradiation with a dose of 50 Gy in 25 fractions combined with a fluoropyrimidine monotherapy. The rate of T down-staging was 49.4% (40/81 evaluable patients). Independent prognostic factors for T down-staging were: age >57 years (p<0.01), cN0 (p<0.01), distance from anal verge >5 cm (p<0.01), initial CEA <6.2 ng/ml (p<0.01), higher number of chemotherapy cycles with Oxaliplatin (pROC=0.05) and protraction of radiotherapy of >35 days (p<0.01). Nine patients from 81 (11.1%) presented complete response (7 pathological and 2 clinical); the independent prognostic factors were stage cT2 versus cT3-4 (p<0.01), initial tumor size ≤3.5 cm and distance from anal verge >5 cm (p=0.03). Sixty-eight patients (79.1%) underwent radical surgery and among them 35 patients (51.5 %) had a sphincter saving procedure. Induction chemotherapy with neoadjuvant chemoradiation produced important down-staging in rectal adenocarcinoma. Independent prognostic factors for T down-staging were: age, cN0, distance from anal verge, initial CEA, the number of Oxaliplatin cycles and duration of radiotherapy; for complete response: cT2, initial tumor size and distance from the anal verge.

Clinical results of definitive-dose (50 Gy/25 fractions) preoperative chemoradiotherapy for unresectable esophageal cancer.

PubMed

Ishikawa, Kazuki; Nakamatsu, Kiyoshi; Shiraishi, Osamu; Yasuda, Takushi; Nishimura, Yasumasa

2015-06-01

The clinical results of definitive-dose preoperative chemoradiotherapy (CRT) of 50 Gy/25 fractions/5 weeks for unresectable esophageal cancer were analyzed. Inclusion criteria were unresectable esophageal squamous cell carcinoma with T4b or mediastinal lymph nodes invading to the trachea or aorta. Radiation therapy of 50 Gy/25 fractions/5 weeks was combined concurrently with two courses of FP therapy (CDDP 70 mg/m(2) + 5-FU 700 mg/m(2)/d × 5 days: day 1-5, day 29-33). Tumor response was evaluated 4 weeks after completion of RT. Subtotal esophagectomy was planned 6-8 weeks after RT. Thirty patients (26 male and 4 female) aged from 50-78 years (median 66) were enrolled between 2008 and 2011. The clinical stages according to the 7th edition of UICC were stages II/III/IV, 1/23/6; T1/2/3/4, 1/1/4/24; and N0/1/2/3, 3/25/1/1. All 30 patients completed RT of 50 Gy/25 fractions. Initial tumor responses were 21 patients with resectable disease, 7 with unresectable disease, and 2 with progressive disease. Subtotal esophagectomy was performed in 18 (60%) of the 30 patients. Pathological complete response was obtained in five (28%) patients. There were two patients with hospitalization death after surgery (11%). Six of the 7 patients who still had unresectable disease were treated with 1-3 courses of docetaxel, CDDP and 5-FU. Three patients treated without surgery showed long-term survival. The 3-year loco-regional control rate and the 3-year overall survival rate for the 30 patients were 70 and 49%, respectively. Definitive-dose preoperative CRT was feasible, and is a promising treatment strategy for unresectable esophageal cancer.

Development of a New Subclavian Arterial Infusion Chemotherapy Method for Locally or Recurrent Advanced Breast Cancer Using an Implanted Catheter-Port System After Redistribution of Arterial Tumor Supply

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

Takizawa, Kenji, E-mail: taki-lrl@vy.catv.ne.jp; Shimamoto, Hiroshi, E-mail: hshima@k8.dion.ne.jp; Ogawa, Yukihisa, E-mail: yukky-p406c@nifty.com

Locally or recurrent advanced breast cancers can receive arterial blood supply from various arteries, such as the internal thoracic artery (ITA), the lateral thoracic artery, and the other small arterial branches originating from the subclavian artery. Failure to catheterize and subsequent formation of collateral arterial blood supply from various arteries are some of the reasons why the response to conventional selective transarterial infusion chemotherapy is limited and variable. To overcome this problem, we developed a new subclavian arterial infusion chemotherapy method using an implanted catheter-port system after redistribution of arterial tumor blood supply by embolizing the ITA. We named thismore » technique ('redistributed subclavian arterial infusion chemotherapy' (RESAIC)). Using RESAIC, patients can be treated on an outpatient basis for extended periods of time. Eleven patients underwent RESAIC, and the complete remission and partial response rate in 10 evaluable patients was 90%: complete remission [CR] n = 4, partial remission n = 4, stable disease n = 1, and not evaluable n = 1. Three of four patients with CR had no distant metastasis, and modified radical mastectomy was performed 1 month after conclusion of RESAIC. The resected specimens showed no residual cancer cells, and pathologically confirmed complete remission was diagnosed in each of these cases. Although temporary grade-3 myelosuppression was seen in three patients who were previously treated by systemic chemotherapy, there was no other drug-induced toxicity or procedure-related complications. RESAIC produced a better response and showed no major complications compared with other studies despite the advanced stage of the cancers.« less

Essential role of hippocampal noradrenaline in the regulation of spatial working memory and TDP-43 tissue pathology.

PubMed

Pintus, Roberta; Riggi, Margherita; Cannarozzo, Cecilia; Valeri, Andrea; de Leo, Gioacchino; Romano, Maurizio; Gulino, Rosario; Leanza, Giampiero

2018-05-01

Extensive loss of noradrenaline-containing neurons and fibers is a nearly invariant feature of Alzheimer's Disease (AD). However, the exact noradrenergic contribution to cognitive and histopathological changes in AD is still unclear. Here, this issue was addressed following selective lesioning and intrahippocampal implantation of embryonic noradrenergic progenitors in developing rats. Starting from about 3 months and up to 12 months post-surgery, animals underwent behavioral tests to evaluate sensory-motor, as well as spatial learning and memory, followed by post-mortem morphometric analyses. At 9 months, Control, Lesioned and Lesion + Transplant animals exhibited equally efficient sensory-motor and reference memory performance. Interestingly, working memory abilities were seen severely impaired in Lesion-only rats and fully recovered in Transplanted rats, and appeared partly lost again 2 months after ablation of the implanted neuroblasts. Morphological analyses confirmed the almost total lesion-induced noradrenergic neuronal and terminal fiber loss, the near-normal reinnervation of the hippocampus promoted by the transplants, and its complete removal by the second lesion. Notably, the noradrenergic-rich transplants normalized also the nuclear expression of the transactive response DNA-binding protein 43 (TDP-43) in various hippocampal subregions, whose cytoplasmic (i.e., pathological) occurrence appeared dramatically increased as a result of the lesions. Thus, integrity of ascending noradrenergic inputs to the hippocampus may be required for the regulation of specific aspects of learning and memory and to prevent TDP-43 tissue pathology. © 2018 Wiley Periodicals, Inc.

Acceleration of diabetic wound healing using a novel protease–anti-protease combination therapy

PubMed Central

Gao, Ming; Nguyen, Trung T.; Suckow, Mark A.; Wolter, William R.; Gooyit, Major; Mobashery, Shahriar; Chang, Mayland

2015-01-01

Nonhealing chronic wounds are major complications of diabetes resulting in >70,000 annual lower-limb amputations in the United States alone. The reasons the diabetic wound is recalcitrant to healing are not fully understood, and there are limited therapeutic agents that could accelerate or facilitate its repair. We previously identified two active forms of matrix metalloproteinases (MMPs), MMP-8 and MMP-9, in the wounds of db/db mice. We argued that the former might play a role in the body’s response to wound healing and that the latter is the pathological consequence of the disease with detrimental effects. Here we demonstrate that the use of compound ND-336, a novel highly selective inhibitor of gelatinases (MMP-2 and MMP-9) and MMP-14, accelerates diabetic wound healing by lowering inflammation and by enhancing angiogenesis and re-epithelialization of the wound, thereby reversing the pathological condition. The detrimental role of MMP-9 in the pathology of diabetic wounds was confirmed further by the study of diabetic MMP-9–knockout mice, which exhibited wounds more prone to healing. Furthermore, topical administration of active recombinant MMP-8 also accelerated diabetic wound healing as a consequence of complete re-epithelialization, diminished inflammation, and enhanced angiogenesis. The combined topical application of ND-336 (a small molecule) and the active recombinant MMP-8 (an enzyme) enhanced healing even more, in a strategy that holds considerable promise in healing of diabetic wounds. PMID:26598687

Acceleration of diabetic wound healing using a novel protease-anti-protease combination therapy.

PubMed

Gao, Ming; Nguyen, Trung T; Suckow, Mark A; Wolter, William R; Gooyit, Major; Mobashery, Shahriar; Chang, Mayland

2015-12-08

Nonhealing chronic wounds are major complications of diabetes resulting in >70,000 annual lower-limb amputations in the United States alone. The reasons the diabetic wound is recalcitrant to healing are not fully understood, and there are limited therapeutic agents that could accelerate or facilitate its repair. We previously identified two active forms of matrix metalloproteinases (MMPs), MMP-8 and MMP-9, in the wounds of db/db mice. We argued that the former might play a role in the body's response to wound healing and that the latter is the pathological consequence of the disease with detrimental effects. Here we demonstrate that the use of compound ND-336, a novel highly selective inhibitor of gelatinases (MMP-2 and MMP-9) and MMP-14, accelerates diabetic wound healing by lowering inflammation and by enhancing angiogenesis and re-epithelialization of the wound, thereby reversing the pathological condition. The detrimental role of MMP-9 in the pathology of diabetic wounds was confirmed further by the study of diabetic MMP-9-knockout mice, which exhibited wounds more prone to healing. Furthermore, topical administration of active recombinant MMP-8 also accelerated diabetic wound healing as a consequence of complete re-epithelialization, diminished inflammation, and enhanced angiogenesis. The combined topical application of ND-336 (a small molecule) and the active recombinant MMP-8 (an enzyme) enhanced healing even more, in a strategy that holds considerable promise in healing of diabetic wounds.

The "Pathological Gambling and Epidemiology" (PAGE) study program: design and fieldwork.

PubMed

Meyer, Christian; Bischof, Anja; Westram, Anja; Jeske, Christine; de Brito, Susanna; Glorius, Sonja; Schön, Daniela; Porz, Sarah; Gürtler, Diana; Kastirke, Nadin; Hayer, Tobias; Jacobi, Frank; Lucht, Michael; Premper, Volker; Gilberg, Reiner; Hess, Doris; Bischof, Gallus; John, Ulrich; Rumpf, Hans-Jürgen

2015-03-01

The German federal states initiated the "Pathological Gambling and Epidemiology" (PAGE) program to evaluate the public health relevance of pathological gambling. The aim of PAGE was to estimate the prevalence of pathological gambling and cover the heterogenic presentation in the population with respect to comorbid substance use and mental disorders, risk and protective factors, course aspects, treatment utilization, triggering and maintenance factors of remission, and biological markers. This paper describes the methodological details of the study and reports basic prevalence data. Two sampling frames (landline and mobile telephone numbers) were used to generate a random sample from the general population consisting of 15,023 individuals (ages 14 to 64) completing a telephone interview. Additionally, high-risk populations have been approached in gambling locations, via media announcements, outpatient addiction services, debt counselors, probation assistants, self-help groups and specialized inpatient treatment facilities. The assessment included two steps: (1) a diagnostic interview comprising the gambling section of the Composite International Diagnostic Interview (CIDI) for case finding; (2) an in-depth clinical interview with participants reporting gambling problems. The in-depth clinical interview was completed by 594 participants, who were recruited from the general or high-risk populations. The program provides a rich epidemiological database which is available as a scientific use file. Copyright © 2015 John Wiley & Sons, Ltd.

[Comorbid psychiatric symptoms in pathological gamblers: anxiety, depression and substance abuse].

PubMed

Dannon, Pinhas; Sason, Marina; Shalgi, Bosmat; Tusan, Lali; Sapir, Yafa; Kotler, Moshe

2004-09-01

Over the centuries, gambling behaviour has been well known and characterized by the combination of pleasure, luck and competition. Our study explored the relationship between pathological gambling, depression and anxiety. We also explored demographic findings and behavioural patterns of the pathological gamblers. Fourty-seven patients were included in this study and they anonymously completed questionnaires which included demographic findings, the Hamilton depression rating scale and the Hamilton anxiety rating scale. The study results demonstrated a strong correlation between depression, anxiety, substance abuse, and pathological gambling. It also presented lower income and higher anxiety levels associated with a higher tendency for gambling. The subjects suffering from depression and anxiety also showed higher levels of suicidality and other abuse dependencies. In order to confirm these preliminary results larger studies are needed in this field.

Residency choices by graduating medical students: why not pathology?

PubMed

Hung, Tawny; Jarvis-Selinger, Sandra; Ford, Jason C

2011-06-01

Pathology is an unpopular residency choice for medical students worldwide. In some countries, this has contributed to a crisis in pathologist human resources that has affected the quality of clinical laboratories. Several previous studies have used information from junior medical students and from residents to suggest ways of improving pathology recruitment. There are, however, no published studies of pathology residency choice that focus on the senior medical students who must be recruited. This study uses focus groups of senior medical students to explore both general and pathology-specific influences on residency choice. Several general influences are identified, including students' expectations for their future clinical practices, their own clinical rotation experiences, influences from other people including mentors, and their choice to reject certain fields. Several specific antipathology influences are also revealed, including negative stereotypes about pathologists, a perceived incompatibility of personality between most medical students (extroverted) and pathologists (introverted), and perceptions of pathologists as being in some ways nonmedical. The most important antipathology influence was that, from the students' perspective, pathology was utterly invisible in clinical practice. Most students did not consider and then reject a pathology residency: instead, pathology was completely ignored. Given the importance of clerkship electives in influencing medical student career choice, promoting clerkship experiences in pathology may improve recruitment. However, departments of pathology must first make pathology visible to students and teach them how pathologists contribute to clinical care. Copyright © 2011 Elsevier Inc. All rights reserved.

Immunotherapy of tuberculosis with Mycobacterium leprae Hsp65 as a DNA vaccine triggers cross-reactive antibodies against mammalian Hsp60 but not pathological autoimmunity.

PubMed

Doimo, Nayara T S; Zárate-Bladés, Carlos R; Rodrigues, Rodrigo F; Tefé-Silva, Cristiane; Trotte, Marcele N S; Souza, Patrícia R M; Soares, Luana S; Rios, Wendy M; Floriano, Elaine M; Brandão, Izaira T; Masson, Ana P; Coelho, Verônica; Ramos, Simone G; Silva, Celio L

2014-01-01

Despite substantial efforts in recent years toward the development of new vaccines and drugs against tuberculosis (TB), success has remained elusive. Immunotherapy of TB with mycobacterial Hsp65 as a DNA vaccine (DNA-hsp65) results in a reduction of systemic bacterial loads and lung tissue damage, but the high homology of Hsp65 with the mammalian protein raises concern that pathological autoimmune responses may also be triggered. We searched for autoimmune responses elicited by DNA-hsp65 immunotherapy in mice chronically infected with TB by evaluating the humoral immune response and comprehensive histopathology using stereology. Cross-reactive antibodies between mycobacterial and mammalian Hsp60/65 were detected; however, no signs of pathological autoimmunity were found up to 60 days after the end of the therapy.

Diet phytochemicals and cutaneous carcinoma chemoprevention: A review.

PubMed

Wang, Siliang; Shen, Peiliang; Zhou, Jinrong; Lu, Yin

2017-05-01

Cutaneous carcinoma, which has occupied a peculiar place among worldwide populations, is commonly responsible for the considerably increasing morbidity and mortality rates. Currently available medical procedures fail to completely avoid cutaneous carcinoma development or to prevent mortality. Cancer chemoprevention, as an alternative strategy, is being considered to reduce the incidence and burden of cancers through chemical agents. Derived from dietary foods, phytochemicals have become safe and reliable compounds for the chemoprevention of cutaneous carcinoma by relieving multiple pathological processes, including oxidative damage, epigenetic alteration, chronic inflammation, angiogenesis, etc. In this review, we presented comprehensive knowledges, main molecular mechanisms for the initiation and development of cutaneous carcinoma as well as effects of various diet phytochemicals on chemoprevention. Copyright © 2017 Elsevier Ltd. All rights reserved.

Additional 4-week capecitabine during the resting periods after 6-week neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer: long-term oncologic outcomes.

PubMed

Park, Sang Woo; Kim, Jin Soo; Kim, Ji Yeon; Lee, Kyung Ha

2018-06-01

The aim of this study was to evaluate the long-term outcome of additional 4-week chemotherapy with capecitabine during the resting periods following a 6-week neoadjuvant chemoradiotherapy (NCRT) regimen, in patients with locally advanced rectal cancer. Radiotherapy was delivered to the whole pelvis at a total dose of 50.4 Gy for 6 weeks. Oral capecitabine was administered at a dose of 825 mg/m 2 twice daily for 10 weeks. Surgery was performed 2-4 weeks following the completion of chemotherapy. Between January 2010 and September 2011, 41 patients completed the scheduled neoadjuvant therapy and surgery. The pathologic complete response rate, 5-year overall survival, and 5-year disease-free survival rates were 22%, 85.4%, and 78.0%, respectively. The 5-year systemic recurrence and 5-year local recurrence rates were 22% and 0%, respectively. Additional 4-week chemotherapy with capecitabine, during the resting periods following a 6-week NCRT regimen, has favorable long-term oncologic outcomes. Further randomized controlled trials are however necessary to evaluate if substantial improvement in local control is achieved with this additional chemotherapy modality for locally advanced rectal cancer.

Cross-protective immune responses between genotypically distinct lineages of infectious laryngotracheitis viruses.

PubMed

Lee, Sang-Won; Markham, Philip F; Coppo, Mauricio J C; Legione, Alistair R; Shil, Niraj K; Quinteros, José A; Noormohammadi, Amir H; Browning, Glenn F; Hartley, Carol A; Devlin, Joanne M

2014-03-01

Recent phylogenetic studies have identified different genotypic lineages of infectious laryngotracheitis virus (ILTV), and these lineages can recombine in the field. The emergence of virulent recombinant field strains of ILTV by natural recombination between commercial vaccines belonging to different genotypic lineages has been reported recently. Despite the use of attenuated ILTV vaccines, these recombinant viruses were able to spread and cause disease in commercial poultry flocks, raising the question of whether the different lineages of ILTV can induce cross-protective immune responses. This study examined the capacity of the Australian-origin A20 ILTV vaccine to protect against challenge with the class 8 ILTV recombinant virus, the genome of which is predominantly derived from a heterologous genotypic lineage. Following challenge, birds vaccinated via eyedrop were protected from clinical signs of disease and pathological changes in the tracheal mucosa, although they were not completely protected from viral infection or replication. In contrast, the challenge virus induced severe clinical signs and tracheal pathology in unvaccinated birds. This is the first study to examine the ability of a vaccine from the Australian lineage to protect against challenge with a virus from a heterologous lineage. These results suggest that the two distinct genotypic lineages of ILTV can both induce cross-protection, indicating that current commercial vaccines are still likely to assist in control of ILTV in the poultry industry, in spite of the emergence of novel recombinants derived from different genotypic lineages.

Radiation necrosis presenting as pseudoprogression (PsP) during alectinib treatment of previously radiated brain metastases in ALK-positive NSCLC: Implications for disease assessment and management.

PubMed

Ou, Sai-Hong Ignatius; Klempner, Samuel J; Azada, Michele C; Rausei-Mills, Veronica; Duma, Christopher

2015-06-01

Radiation necrosis presenting as pseudoprogression (PsP) is relatively common after radiation and temozolomide (TMZ) treatment in glioblastoma multiforme (GBM), especially among patients with GBM that harbors intrinsic increased responsiveness to TMZ (methylated O6-methylguanine-DNA methyltransferase [MGMT] promoter). Alectinib is a second generation ALK inhibitor that has significant CNS activity against brain metastases in anaplastic lymphoma kinase (ALK)-rearranged (ALK+) non-small cell lung cancer (NSCLC) patients. We report 2 ALK+ NSCLC patients who met RECIST criteria for progressive disease by central radiologic review due to increased in size from increased contrast enhancement in previously stereotactically radiated brain metastases with ongoing extra-cranial response to alectinib. In both patients alectinib was started within 4 months of completing stereotactic radiosurgery (SRS). The enlarging lesions in both patients were resected and found to have undergone extensive necrosis with no residual tumor pathologically. PsP was incorrectly classified as progressive disease even by central independent imaging review. Treatment-related necrosis of previously SRS-treated brain metastasis during alectinib treatment can present as PsP. It may be impossible to distinguish PsP from true disease progression without a pathologic examination from resected sample. High degree of clinical suspicion, close monitoring and more sensitive imaging modalities may be needed to distinguish PsP versus progression in radiated brain lesions during alectinib treatment especially if there is no progression extra-cranially. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Attention problems and pathological gaming: resolving the 'chicken and egg' in a prospective analysis.

PubMed

Ferguson, Christopher J; Ceranoglu, T Atilla

2014-03-01

Pathological gaming (PG) behaviors are behaviors which interfere with other life responsibilities. Continued debate exists regarding whether symptoms of PG behaviors are a unique phenomenon or arise from other mental health problems, including attention problems. Development of attention problems and occurrence of pathological gaming in 144 adolescents were followed during a 1-year prospective analysis. Teens and their parents reported on pathological gaming behaviors, attention problems, and current grade point average, as well as several social variables. Results were analyzed using regression and path analysis. Attention problems tended to precede pathological gaming behaviors, but the inverse was not true. Attention problems but not pathological gaming predicted lower GPA 1 year later. Current results suggest that pathological gaming arises from attention problems, but not the inverse. These results suggest that pathological gaming behaviors are symptomatic of underlying attention related mental health issues, rather than a unique phenomenon.

Commentary on "Prognostic effect of carcinoma in situ in muscle-invasive urothelial carcinoma patients receiving neoadjuvant chemotherapy."

PubMed

Thomas, D E; Kaimakliotis, H Z; Rice, K R; Pereira, J A; Johnston, P; Moore, M L; Reed, A; Cregar, D M; Franklin, C; Loman, R L; Koch, M O; Bihrle, R; Foster, R S; Masterson, T A; Gardner, T A; Sundaram, C P; Powell, C R; Beck, Sdw; Grignon, D J; Cheng, L; Albany, C; Hahn, N M

2018-07-01

Carcinoma in situ (CIS) is a poor prognostic finding in urothelial carcinoma. However, its significance in muscle-invasive urothelial carcinoma (MIUC) treated with neoadjuvant chemotherapy (NAC) is uncertain. We assessed the effect of CIS found in pretreatment transurethral resection of bladder tumor (TURBT) biopsies on the pathologic and clinical outcomes. Subjects with MIUC treated with NAC before cystectomy were identified. The pathologic complete response (pCR) rates stratified by TURBT CIS status were compared. The secondary analyses included tumor response, progression-free survival (PFS), overall survival (OS), and an exploratory post hoc analysis of patients with pathologic CIS only (pTisN0) at cystectomy. A total of 137 patients with MIUC were identified. TURBT CIS was noted in 30.7% of the patients. The absence of TURBT CIS was associated with a significantly increased pCR rate (23.2% vs. 9.5%; odds ratio = 4.08; 95% CI: 1.19-13.98; P = 0.025). Stage pTisN0 disease was observed in 19.0% of the TURBT CIS patients. TURBT CIS status did not significantly affect the PFS or OS outcomes. Post hoc analysis of the pTisN0 patients revealed prolonged median PFS (104.5 vs. 139.9 months; P = 0.055) and OS (104.5 vs. 152.3 months; P = 0.091) outcomes similar to those for the pCR patients. The absence of CIS on pretreatment TURBT in patients with MIUC undergoing NAC was associated with increased pCR rates, with no observed differences in PFS or OS. Isolated CIS at cystectomy was frequently observed, with lengthy PFS and OS durations similar to those for pCR patients. Further studies aimed at understanding the biology and clinical effect of CIS in MIUC are warranted. Copyright © 2018 Elsevier Inc. All rights reserved.

Outcomes After Diagnostic Hip Injection.

PubMed

Lynch, T Sean; Steinhaus, Michael E; Popkin, Charles A; Ahmad, Christopher S; Rosneck, James

2016-08-01

To provide a comprehensive review of outcomes associated with local anesthetic (LA) or LA and corticosteroid (CS) diagnostic hip injections, and how well response predicts subsequent operative success. A systematic review from database (PubMed, Medline, Scopus, Embase) inception to January 2015 for English-language articles reporting primary patient outcomes data was performed, excluding studies with >50% underlying osteoarthritis. Studies were assessed by 2 reviewers who collected pertinent data. Seven studies were included, reporting on a total 337 patients undergoing diagnostic hip injection. The mean age was 34.4 years, with 5 studies reporting 94 (35.2%) males and 173 (64.8%) females. One study examined the rate of pain relief with LA (92.5%); 2 CS studies reported relief on a scale from 0% to 100% (no to complete relief), ranging from 61% to 82.3%; and 3 studies used 10-point pain scales, with a CS study noting a pain score of 1.0, an LA study with a score of 3.03, and 1 study using either CS or LA scores of 3 to 5.6. Duration of pain relief was 9.8 (CS) and 2.35 days (LA). By pathology, greatest relief was achieved in acetabular chondral injury (93.3%) and least in cam impingement (81.6%), with clinical and imaging findings being unreliable predictors of relief. One study showed nonresponse to be a strong predictor of negative surgical outcome for femoroacetabular impingement. Diagnostic hip injections provide substantial pain relief for patients with various hip pathologies, with limited data to suggest greatest relief for those with chondral injury. Clinical and imaging findings are unreliable predictors of injection response, and nonresponse to injection is a strong negative predictor of surgical outcome. Future research should focus on elucidating differences by underlying pathology and predicting future operative success. Level IV, systematic review. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Intensity-Modulated Radiation Therapy With Concurrent Chemotherapy as Preoperative Treatment for Localized Gastric Adenocarcinoma

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

Chakravarty, Twisha; Crane, Christopher H.; Ajani, Jaffer A.

2012-06-01

Purpose: The goal of this study was to evaluate dosimetric parameters, acute toxicity, pathologic response, and local control in patients treated with preoperative intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy for localized gastric adenocarcinoma. Methods: Between November 2007 and April 2010, 25 patients with localized gastric adenocarcinoma were treated with induction chemotherapy, followed by preoperative IMRT and concurrent chemotherapy and, finally, surgical resection. The median radiation therapy dose was 45 Gy. Concurrent chemotherapy was 5-fluorouracil and oxaliplatin in 18 patients, capecitabine in 3, and other regimens in 4. Subsequently, resection was performed with total gastrectomy in 13 patients, subtotal gastrectomymore » in 7, and other surgeries in 5. Results: Target coverage, expressed as the ratio of the minimum dose received by 99% of the planning target volume to the prescribed dose, was a median of 0.97 (range, 0.92-1.01). The median V{sub 30} (percentage of volume receiving at least 30 Gy) for the liver was 26%; the median V{sub 20} (percentage of volume receiving at least 20 Gy) for the right and left kidneys was 14% and 24%, respectively; and the median V{sub 40} (percentage of volume receiving at least 40 Gy) for the heart was 18%. Grade 3 acute toxicity developed in 14 patients (56%), including dehydration in 10, nausea in 8, and anorexia in 5. Grade 4 acute toxicity did not develop in any patient. There were no significant differences in the rates of acute toxicity, hospitalization, or feeding tube use in comparison to those in a group of 50 patients treated with preoperative three-dimensional conformal radiation therapy with concurrent chemotherapy. R0 resection was obtained in 20 patients (80%), and pathologic complete response occurred in 5 (20%). Conclusions: Preoperative IMRT for gastric adenocarcinoma was well tolerated, accomplished excellent target coverage and normal structure sparing, and led to appropriate pathologic outcomes.« less

Prognostic Effect of Carcinoma In Situ in Muscle-invasive Urothelial Carcinoma Patients Receiving Neoadjuvant Chemotherapy.

PubMed

Thomas, Derek E; Kaimakliotis, Hristos Z; Rice, Kevin R; Pereira, Jose A; Johnston, Paul; Moore, Marietta L; Reed, Angela; Cregar, Dylan M; Franklin, Cindy; Loman, Rhoda L; Koch, Michael O; Bihrle, Richard; Foster, Richard S; Masterson, Timothy A; Gardner, Thomas A; Sundaram, Chandru P; Powell, Charles R; Beck, Stephen D W; Grignon, David J; Cheng, Liang; Albany, Costantine; Hahn, Noah M

2017-08-01

Carcinoma in situ (CIS) is a poor prognostic finding in urothelial carcinoma. However, its significance in muscle-invasive urothelial carcinoma (MIUC) treated with neoadjuvant chemotherapy (NAC) is uncertain. We assessed the effect of CIS found in pretreatment transurethral resection of bladder tumor (TURBT) biopsies on the pathologic and clinical outcomes. Subjects with MIUC treated with NAC before cystectomy were identified. The pathologic complete response (pCR) rates stratified by TURBT CIS status were compared. The secondary analyses included tumor response, progression-free survival (PFS), overall survival (OS), and an exploratory post hoc analysis of patients with pathologic CIS only (pTisN0) at cystectomy. A total of 137 patients with MIUC were identified. TURBT CIS was noted in 30.7% of the patients. The absence of TURBT CIS was associated with a significantly increased pCR rate (23.2% vs. 9.5%; odds ratio, 4.08; 95% confidence interval, 1.19-13.98; P = .025). Stage pTisN0 disease was observed in 19.0% of the TURBT CIS patients. TURBT CIS status did not significantly affect the PFS or OS outcomes. Post hoc analysis of the pTisN0 patients revealed prolonged median PFS (104.5 vs. 139.9 months; P = .055) and OS (104.5 vs. 152.3 months; P = .091) outcomes similar to those for the pCR patients. The absence of CIS on pretreatment TURBT in patients with MIUC undergoing NAC was associated with increased pCR rates, with no observed differences in PFS or OS. Isolated CIS at cystectomy was frequently observed, with lengthy PFS and OS durations similar to those for pCR patients. Further studies aimed at understanding the biology and clinical effect of CIS in MIUC are warranted. Copyright © 2016 Elsevier Inc. All rights reserved.

Neural correlates of an attentional bias to health-threatening stimuli in individuals with pathological health anxiety.

PubMed

Mier, Daniela; Bailer, Josef; Ofer, Julia; Kerstner, Tobias; Zamoscik, Vera; Rist, Fred; Witthöft, Michael; Diener, Carsten

2017-05-01

An attentional bias to health-threat stimuli is assumed to represent the primary pathogenetic factor for the development and maintenance of pathological health anxiety (PHA; formerly termed "hypochondriasis"). However, little is known about the neural basis of this attentional bias in individuals with PHA. A group of patients with PHA, a group of depressed patients and a healthy control group completed an emotional Stroop task with health-threat (body symptom and illness) words and neutral control words while undergoing functional MRI. We included 33 patients with PHA, 28 depressed patients and 31 controls in our analyses. As reflected in reaction times, patients with PHA showed a significantly stronger attentional bias to health-threat words than both control groups. In addition, patients with PHA showed increased amygdala and rostral anterior cingulate cortex activation for body symptom, but not for illness words. Moreover, only in patients with PHA amygdala activation in response to symptom words was positively associated with higher arousal and more negative valence ratings of the body symptom word material. A control group of patients with an anxiety disorder but without PHA would have helped to define the specificity of the results for PHA. The attentional bias observed in patients with PHA is associated with hyperactivation in response to body symptom words in brain regions that are crucial for an arousal-related fear response (e.g., the amygdala) and for resolving emotional interference (e.g., the rostral anterior cingulate cortex). The findings have important implications for the nosological classification of PHA and suggest the application of innovative exposure-based interventions for the treatment of PHA.

Neural correlates of an attentional bias to health-threatening stimuli in individuals with pathological health anxiety

PubMed Central

Mier, Daniela; Bailer, Josef; Ofer, Julia; Kerstner, Tobias; Zamoscik, Vera; Rist, Fred; Witthöft, Michael; Diener, Carsten

2017-01-01

Background An attentional bias to health-threat stimuli is assumed to represent the primary pathogenetic factor for the development and maintenance of pathological health anxiety (PHA; formerly termed “hypochondriasis”). However, little is known about the neural basis of this attentional bias in individuals with PHA. Methods A group of patients with PHA, a group of depressed patients and a healthy control group completed an emotional Stroop task with health-threat (body symptom and illness) words and neutral control words while undergoing functional MRI. Results We included 33 patients with PHA, 28 depressed patients and 31 controls in our analyses. As reflected in reaction times, patients with PHA showed a significantly stronger attentional bias to health-threat words than both control groups. In addition, patients with PHA showed increased amygdala and rostral anterior cingulate cortex activation for body symptom, but not for illness words. Moreover, only in patients with PHA amygdala activation in response to symptom words was positively associated with higher arousal and more negative valence ratings of the body symptom word material. Limitations A control group of patients with an anxiety disorder but without PHA would have helped to define the specificity of the results for PHA. Conclusion The attentional bias observed in patients with PHA is associated with hyperactivation in response to body symptom words in brain regions that are crucial for an arousal-related fear response (e.g., the amygdala) and for resolving emotional interference (e.g., the rostral anterior cingulate cortex). The findings have important implications for the nosological classification of PHA and suggest the application of innovative exposure-based interventions for the treatment of PHA. PMID:28234209

TGFbeta1 (Leu10Pro), p53 (Arg72Pro) can predict for increased risk for breast cancer in south Indian women and TGFbeta1 Pro (Leu10Pro) allele predicts response to neo-adjuvant chemo-radiotherapy.

PubMed

Rajkumar, Thangarajan; Samson, Mani; Rama, Ranganathan; Sridevi, Veluswami; Mahji, Urmila; Swaminathan, Rajaraman; Nancy, Nirmala K

2008-11-01

The breast cancer incidence has been increasing in the south Indian women. A case (n=250)-control (n=500) study was undertaken to investigate the role of Single Nucleotide Polymorphisms (SNP's) in GSTM1 (Present/Null); GSTP1 (Ile105Val), p53 (Arg72Pro), TGFbeta1 (Leu10Pro), c-erbB2 (Ile655Val), and GSTT1 (Null/Present) in breast cancer. In addition, the value of the SNP's in predicting primary tumor's pathologic response following neo-adjuvant chemo-radiotherapy was assessed. Genotyping was done using PCR (GSTM1, GSTT1), Taqman Allelic discrimination assay (GSTP1, c-erbB2) and PCR-CTPP (p53 and TGFbeta1). None of the gene SNP's studied were associated with a statistically significant increased risk for the breast cancer. However, combined analysis of the SNP's showed that p53 (Arg/Arg and Arg/Pro) with TGFbeta1 (Pro/Pro and Leu/Pro) were associated with greater than 2 fold increased risk for breast cancer in Univariate (P=0.01) and Multivariate (P=0.003) analysis. There was no statistically significant association for the GST family members with the breast cancer risk. TGFbeta1 (Pro/Pro) allele was found to predict complete pathologic response in the primary tumour following neo-adjuvant chemo-radiotherapy (OR=6.53 and 10.53 in Univariate and Multivariate analysis respectively) (P=0.004) and was independent of stage. This study suggests that SNP's can help predict breast cancer risk in south Indian women and that TGFbeta1 (Pro/Pro) allele is associated with a better pCR in the primary tumour.

Pre-operative assessment of residual disease in locally advanced breast cancer patients: A sequential study by quantitative diffusion weighted MRI as a function of therapy.

PubMed

Agarwal, Khushbu; Sharma, Uma; Sah, Rani G; Mathur, Sandeep; Hari, Smriti; Seenu, Vurthaluru; Parshad, Rajinder; Jagannathan, Naranamangalam R

2017-10-01

The potential of diffusion weighted imaging (DWI) in assessing pathologic response and surgical margins in locally advanced breast cancer patients (n=38) undergoing neoadjuvant chemotherapy was investigated. DWI was performed at pre-therapy (Tp0), after I (Tp1) and III (Tp3) NACT at 1.5T. Apparent diffusion coefficient (ADC) of whole tumor (ADC WT ), solid tumor (ADC ST ), intra-tumoral necrosis (ADC Nec ) was determined. Further, ADC of 6 consecutive shells (5mm thickness each) including tumor margin to outside tumor margins (OM1 to OM5) was calculated and the data analyzed to define surgical margins. Of 38 patients, 6 were pathological complete responders (pCR), 19 partial responders (pPR) and 13 were non-responders (pNR). Significant increase was observed in ADC ST and ADC WT in pCR and pPR following therapy. Pre-therapy ADC was significantly lower in pCR compared to pPR and pNR indicating the heterogeneous nature of tumor which may affect drug perfusion and consequently the response. ADC of outside margins (OM1, OM2, and OM3) was significantly different among pCR, pPR and pNR at Tp3 which may serve as response predictive parameter. Further, at Tp3, ADC of outside margins (OM1, OM2, and OM3) was significantly lower compared to that seen at Tp0 in pCR, indicating the presence of residual disease in these shells. Pre-surgery information may serve as a guide to define cancer free margins and the extent of residual disease which may be useful in planning breast conservation surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

Dyke-Davidoff-Masson syndrome: case report of fetal unilateral ventriculomegaly and hypoplastic left middle cerebral artery.

PubMed

Piro, Ettore; Piccione, Maria; Marrone, Gianluca; Giuffrè, Mario; Corsello, Giovanni

2013-05-14

Prenatal ultrasonographic detection of unilateral cerebral ventriculomegaly arises suspicion of pathological condition related to cerebrospinal fluid flow obstruction or cerebral parenchimal pathology. Dyke-Davidoff-Masson syndrome is a rare condition characterized by cerebral hemiatrophy, calvarial thickening, skull and facial asymmetry, contralateral hemiparesis, cognitive impairment and seizures. Congenital and acquired types are recognized and have been described, mainly in late childhood, adolescence and adult ages. We describe a female infant with prenatal diagnosis of unilateral left ventriculomegaly in which early brain MRI and contrast enhanced-MRI angiography, showed cerebral left hemiatrophy associated with reduced caliber of the left middle cerebral artery revealing the characteristic findings of the Dyke-Davidoff-Masson syndrome. Prenatal imaging, cerebral vascular anomaly responsible for the cerebral hemiatrophy and the early clinical evolution have never been described before in such a young child and complete the acquired clinical descriptions in older children. Differential diagnosis, genetic investigations, neurophysiologic assessments, short term clinical and developmental follow up are described. Dyke-Davidoff-Masson syndrome must be ruled out in differential diagnosis of fetal unilateral ventriculomegaly. Early clinical assessment, differential diagnosis and cerebral imaging including cerebral MRI angiography allow the clinicians to diagnose also in early infancy this rare condition.

Validity of a gambling scale for the addiction severity index.

PubMed

Petry, Nancy M

2003-06-01

This study assessed the validity of an adaptation of the Addiction Severity Index (ASI) for evaluating severity of gambling problems. Participants (N = 597) from four different populations (pathological gamblers enrolled in a treatment study, pathological gamblers initiating outpatient treatment at a community-based program, frequent gamblers recruited from advertisement, and substance abusers) completed the ASI, along with a supplemental gambling subscale (ASI-G). Internal consistency of the ASI-G was good (alpha =.90), and a principal components analysis indicated a single factor explained 73% of the variance in responses. ASI-G scores demonstrated excellent convergent validity with other measures of gambling and convergent validity with external sources, including collateral informant and clinician-rated reports. ASI-G scores discriminated among the samples tested. Temporal stability of ASI-G scores was high during a 1-month period for patients with substance abuse disorder who were not seeking gambling treatment. For treatment-seeking gamblers, the number of treatment sessions attended was significantly associated with reductions in ASI-G scores. Together, these data suggest that the ASI-G subscale may be a useful tool for assessing severity of gambling problems in a variety of populations.

Nomogram predicting response after chemoradiotherapy in rectal cancer using sequential PETCT imaging: a multicentric prospective study with external validation.

PubMed

van Stiphout, Ruud G P M; Valentini, Vincenzo; Buijsen, Jeroen; Lammering, Guido; Meldolesi, Elisa; van Soest, Johan; Leccisotti, Lucia; Giordano, Alessandro; Gambacorta, Maria A; Dekker, Andre; Lambin, Philippe

2014-11-01

To develop and externally validate a predictive model for pathologic complete response (pCR) for locally advanced rectal cancer (LARC) based on clinical features and early sequential (18)F-FDG PETCT imaging. Prospective data (i.a. THUNDER trial) were used to train (N=112, MAASTRO Clinic) and validate (N=78, Università Cattolica del S. Cuore) the model for pCR (ypT0N0). All patients received long-course chemoradiotherapy (CRT) and surgery. Clinical parameters were age, gender, clinical tumour (cT) stage and clinical nodal (cN) stage. PET parameters were SUVmax, SUVmean, metabolic tumour volume (MTV) and maximal tumour diameter, for which response indices between pre-treatment and intermediate scan were calculated. Using multivariate logistic regression, three probability groups for pCR were defined. The pCR rates were 21.4% (training) and 23.1% (validation). The selected predictive features for pCR were cT-stage, cN-stage, response index of SUVmean and maximal tumour diameter during treatment. The models' performances (AUC) were 0.78 (training) and 0.70 (validation). The high probability group for pCR resulted in 100% correct predictions for training and 67% for validation. The model is available on the website www.predictcancer.org. The developed predictive model for pCR is accurate and externally validated. This model may assist in treatment decisions during CRT to select complete responders for a wait-and-see policy, good responders for extra RT boost and bad responders for additional chemotherapy. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Molecular Mechanisms Underlying Cardiac Adaptation to Exercise

PubMed Central

Vega, Rick B.; Konhilas, John P.; Kelly, Daniel P.; Leinwand, Leslie A.

2017-01-01

Exercise elicits coordinated multi-organ responses including skeletal muscle, vasculature, heart and lung. In the short term, the output of the heart increases to meet the demand of strenuous exercise. Long term exercise instigates remodeling of the heart including growth and adaptive molecular and cellular re-programming. Signaling pathways such as the insulin-like growth factor 1/PI3K/Akt pathway mediate many of these responses. Exercise-induced, or physiologic, cardiac growth contrasts with growth elicited by pathological stimuli such as hypertension. Comparing the molecular and cellular underpinnings of physiologic and pathologic cardiac growth has unveiled phenotype-specific signaling pathways and transcriptional regulatory programs. Studies suggest that exercise pathways likely antagonize pathological pathways, and exercise training is often recommended for patients with chronic stable heart failure or following myocardial infarction. Herein, we summarize the current understanding of the structural and functional cardiac responses to exercise as well as signaling pathways and downstream effector molecules responsible for these adaptations. PMID:28467921

Signal Transducer and Activator of Transcription Factor 6 Signaling Contributes to Control Host Lung Pathology but Favors Susceptibility against Toxocara canis Infection

PubMed Central

Faz-López, Berenice; Ledesma-Soto, Yadira; Romero-Sánchez, Yolanda; Calleja, Elsa; Martínez-Labat, Pablo; Terrazas, Luis I.

2013-01-01

Using STAT6−/− BALB/c mice, we have analyzed the role of STAT6-induced Th2 response in determining the outcome of experimental toxocariasis caused by embryonated eggs of the helminth parasite Toxocara canis. Following T. canis infection wild-type BALB/c mice developed a strong Th2-like response, produced high levels of IgG1, IgE, and IL-4, recruited alternatively activated macrophages, and displayed a moderate pathology in the lungs; however, they harbored heavy parasite loads in different tissues. In contrast, similarly infected STAT6−/− BALB/c mice mounted a weak Th2-like response, did not recruit alternatively activated macrophages, displayed a severe pathology in the lungs, but efficiently controlled T. canis infection. These findings demonstrate that Th2-like response induced via STAT6-mediated signaling pathway mediates susceptibility to larval stage of T. canis. Furthermore, they also indicate that unlike most gastrointestinal helminths, immunity against larvae of T. canis is not mediated by a Th2-dominant response. PMID:23509764

Low Estrogen Receptor (ER)-Positive Breast Cancer and Neoadjuvant Systemic Chemotherapy: Is Response Similar to Typical ER-Positive or ER-Negative Disease?

PubMed

Landmann, Alessandra; Farrugia, Daniel J; Zhu, Li; Diego, Emilia J; Johnson, Ronald R; Soran, Atilla; Dabbs, David J; Clark, Beth Z; Puhalla, Shannon L; Jankowitz, Rachel C; Brufsky, Adam M; Ahrendt, Gretchen M; McAuliffe, Priscilla F; Bhargava, Rohit

2018-05-08

Pathologic complete response (pCR) rate after neoadjuvant chemotherapy was compared between 141 estrogen receptor (ER)-negative (43%), 41 low ER+ (13%), 47 moderate ER+ (14%), and 98 high ER+ (30%) tumors. Human epidermal growth factor receptor 2-positive cases, cases without semiquantitative ER score, and patients treated with neoadjuvant endocrine therapy alone were excluded. The pCR rate of low ER+ tumors was similar to the pCR rate of ER- tumors (37% and 26% for low ER and ER- respectively, P = .1722) but significantly different from the pCR rate of moderately ER+ (11%, P = .0049) and high ER+ tumors (4%, P < .0001). Patients with pCR had an excellent prognosis regardless of the ER status. In patients with residual disease (no pCR), the recurrence and death rate were higher in ER- and low ER+ cases compared with moderate and high ER+ cases. Low ER+ breast cancers are biologically similar to ER- tumors. Semiquantitative ER H-score is an important determinant of response to neoadjuvant chemotherapy.

Retrospective Review of Positron Emission Tomography With Contrast-Enhanced Computed Tomography in the Posttreatment Setting in Human Papillomavirus–Associated Oropharyngeal Carcinoma

PubMed Central

Chan, Jason Y. K.; Sanguineti, Giuseppe; Richmon, Jeremy D.; Marur, Shanthi; Gourin, Christine G.; Koch, Wayne; Chung, Christine H.; Quon, Harry; Bishop, Justin A.; Aygun, Nafi; Agrawal, Nishant

2013-01-01

Objective To determine the value of positron emission tomography (PET) with contrast-enhanced computed tomography (CT) in assessing the need for neck dissection by retrospectively reviewing the pathology reports of patients with human papillomavirus (HPV)- associated oropharyngeal squamous cell carcinoma (SCC). Design Retrospective cohort study. Setting Tertiary medical center. Patients Seventy-seven patients with HPV-related SCC. Main Outcome Measures Seventy-seven consecutive patients with a diagnosis of HPV-related SCC who were treated with radiotherapy as the primary treatment between August 2007 and October 2010 were retrospectively evaluated for radiologic and pathologic rate of persistence of nodal metastasis after completion of definitive radiotherapy. Pretreatment and posttreatment imaging included contrast-enhanced CT and PET. Response to treatment was measured on CT, PET at standardized uptake value (SUV) thresholds of 2 and 2.5, and PET/CT by a neuroradiologist in a blinded fashion. Then, the pathology report of the patients who underwent neck dissections was reviewed for nodal status after resection and correlated with the imaging findings. Results Of the 77 patients, 67 met the study criteria, with an average follow-up PET/CT scan at 90.5 days after completion of radiotherapy. Ten patients did not undergo follow-up PET/CT imaging. Twenty patients underwent neck dissections after completion of radiation therapy. Of these 20 patients, 4 had persistent tumor and 16 did not have viable tumor. Using the final pathology report to correlate with imaging responses, CT had a negative predictive value (NPV) of 85.7% (95% CI, 48.7%-97.4%), PET with SUV thresholds of 2 had an NPV of 91.7% (95% CI, 64.6%-98.5%), PET with a cutoff SUV of 2.5 had an NPV of 85.7% (95% CI, 60.1%-96.0%), PET/CT with an SUV of 2 had an NPV of 100% (95% CI, 59.8%-100.0%), and PET/CT with an SUV of 2.5 had an NPV of 85.7% (95% CI, 48.7%-97.4%). The 47 patients who did not undergo neck dissection had a median follow-up of 26 months without an isolated neck failure. Analysis of all 67 patients in the cohort revealed the following values: CT had an NPV of 95.7% (95% CI, 85.8%-98.8%), PET with an SUV of 2 had an NPV of 98.2% (95% CI, 90.4%-99.7%), PET with an SUV of 2.5 had an NPV of 95.0% (95% CI, 86.3%-98.3%), PET/CT with an SUV of 2 had an NPV of 100.0% (95% CI, 92.0%-100.0%), and PET/CT with an SUV of 2.5 had an NPV of 95.7% (95% CI, 85.8%-98.8%). Conclusions Positron emission tomography combined with contrast-enhanced CT has a better NPV than either imaging modality alone in patients with HPV-associated oropharyngeal SCC. Furthermore, PET/CT with an SUV threshold of 2 used in patients with HPV-related SCC offers an imaging modality with a high NPV that may obviate the need for unnecessary neck dissections. PMID:23165378

Neoadjuvant Sandwich Treatment With Oxaliplatin and Capecitabine Administered Prior to, Concurrently With, and Following Radiation Therapy in Locally Advanced Rectal Cancer: A Prospective Phase 2 Trial

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

Gao, Yuan-Hong; Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou; Lin, Jun-Zhong

Purpose: Systemic failure remains the major challenge in management of locally advanced rectal cancer (LARC). To optimize the timing of neoadjuvant treatment and enhance systemic control, we initiated a phase 2 trial to evaluate a new strategy of neoadjuvant sandwich treatment, integrating induction chemotherapy, concurrent chemoradiation therapy, and consolidation chemotherapy. Here, we present preliminary results of this trial, reporting the tumor response, toxicities, and surgical complications. Methods and Materials: Fifty-one patients with LARC were enrolled, among which were two patients who were ineligible because of distant metastases before treatment. Patients were treated first with one cycle of induction chemotherapy consistingmore » of oxaliplatin, 130 mg/m² on day 1, with capecitabine, 1000 mg/m² twice daily for 14 days every 3 weeks (the XELOX regimen), followed by chemoradiation therapy, 50 Gy over 5 weeks, with the modified XELOX regimen (oxaliplatin 100 mg/m²), and then with another cycle of consolidation chemotherapy with the XELOX regimen. Surgery was performed 6 to 8 weeks after completion of radiation therapy. Tumor responses, toxicities, and surgical complications were recorded. Results: All but one patent completed the planned schedule of neoadjuvant sandwich treatment. Neither life-threatening blood count decrease nor febrile neutropenia were observed. Forty-five patents underwent optimal surgery with total mesorectal excision (TME). Four patients refused surgery because of clinically complete response. There was no perioperative mortality in this cohort. Five patients (11.1%) developed postoperative complications. Among the 45 patients who underwent TME, pathologic complete response (pCR), pCR or major regression, and at least moderate regression were achieved in 19 (42.2%), 37 (82.2%), and 44 patients (97.8%), respectively. Conclusions: Preliminary results suggest that the strategy of neoadjuvant sandwich treatment using XELOX regimen as induction, concomitant, and consolidation chemotherapy to the conventional radiation is well tolerated. The strategy is highly effective in terms of pCR and major regression, which warrants further investigation.« less

A leadership-management training curriculum for pathology residents.

PubMed

Sims, K L; Darcy, T P

1997-07-01

Leadership and management skills are increasingly critical to the success of pathologists in and outside of academic centers. We describe a leadership and management curriculum in a combined anatomic and clinical pathology residency program. The mentor-based approach incorporates leadership and management skills throughout the residency with a dedicated 2-month rotation during the final year of training. This 2-month rotation is led by a senior faculty pathologist mentor and includes active participation in management activities, small group discussions, reading, and a management process project. The topics for the small group discussions, reading list, mentor-based activities, and completed management process projects are described. Outcomes and evaluations are reported for residents who have completed this curriculum in leadership and management.

Prevention of the Post-traumatic Fibrotic Response in Joints

DTIC Science & Technology

2014-10-01

an experimental model in mice. The American journal of forensic medicine and pathology . 1988; 9(4):310-2. 14 APPENDICES: An abstract...ongoing study addresses the critical clinical problem of posttraumatic joint stiffness, a pathology that reduces the range of motion (ROM) of injured...joints and contributes to the development of osteoarthritis. The fundamental hypothesis that drives the current study is that pathological fibrotic

Going fully digital: Perspective of a Dutch academic pathology lab

PubMed Central

Stathonikos, Nikolas; Veta, Mitko; Huisman, André; van Diest, Paul J.

2013-01-01

During the last years, whole slide imaging has become more affordable and widely accepted in pathology labs. Digital slides are increasingly being used for digital archiving of routinely produced clinical slides, remote consultation and tumor boards, and quantitative image analysis for research purposes and in education. However, the implementation of a fully digital Pathology Department requires an in depth look into the suitability of digital slides for routine clinical use (the image quality of the produced digital slides and the factors that affect it) and the required infrastructure to support such use (the storage requirements and integration with lab management and hospital information systems). Optimization of digital pathology workflow requires communication between several systems, which can be facilitated by the use of open standards for digital slide storage and scanner management. Consideration of these aspects along with appropriate validation of the use of digital slides for routine pathology can pave the way for pathology departments to go “fully digital.” In this paper, we summarize our experiences so far in the process of implementing a fully digital workflow at our Pathology Department and the steps that are needed to complete this process. PMID:23858390

[Depression, deliberate self-harm and suicidal behaviour in adolescents engaging in risky and pathological internet use].

PubMed

Fischer, Gloria; Brunner, Romuald; Parzer, Peter; Klug, Katja; Durkee, Tony; Carli, Vladimi; Wasserman, Danuta; Vonderlin, Eva; Resch, Franz; Kaess, Michael

2012-01-01

To investigate associations between risky and pathologic internet use with depression, deliberate self-harm and suicidal behaviour among a representative sample of German adolescents. A total of 1,435 students (48% boys, 52% girls) from the area of Heidelberg/Germany were recruited during the SEYLE study, a European school-based intervention study and completed an assessment of different questionnaires, including the Young Diagnostic Questionnaire for the assessment of risky and pathological internet use, the Beck Depression Inventory, the Deliberate Self Harm Inventory, and the Paykel Suicide Scale. 80.7% of the students reported regular, 14.5% risky, and 4.8% pathological internet use. The risky and the pathological internet users showed significant higher rates of depression, deliberate self-harm and suicidal behaviour compared to students with regular internet use. Remarkably, there were no significant differences of levels of depression and suicidal behaviour between risky and pathological users. These results suggest that not only pathologic internet use but also risky internet use is associated with symptoms of depression, self-harm and suicidal behaviour. Therefore, more attention should be paid to adolescents with risky internet use for the early recognition of depression, self-harm and suicidality in adolescence.

Food insecurity and eating disorder pathology.

PubMed

Becker, Carolyn Black; Middlemass, Keesha; Taylor, Brigitte; Johnson, Clara; Gomez, Francesca

2017-09-01

The primary aim of this study was to investigate eating disorder (ED) pathology in those living with food insecurity. A secondary aim was to investigate whether any-reason dietary restraint, weight self-stigma, and worry increased as level of food insecurity increased. Participants (N = 503) seeking food from food pantries completed questionnaires assessing level of food insecurity, demographics, ED pathology, dietary restraint, weight self-stigma, and worry. Consistent with hypotheses, participants with the highest level of food insecurity (i.e., adults who reported having hungry children in their household) also endorsed significantly higher levels of binge eating, overall ED pathology, any-reason dietary restraint, weight self-stigma, and worry compared to participants with lower levels of food insecurity. Contrary to hypotheses, compensatory behaviors also increased as level of food insecurity worsened. Overall, 17% of those in the child hunger food insecurity group reported clinically significant ED pathology. This is the first study to assess the full spectrum of ED pathology in a low-income, marginalized population with food insecurity. Given that food insecurity is a global concern, results from this study suggest that greater attention to the association between ED pathology and food insecurity is warranted by researchers around the world. © 2017 Wiley Periodicals, Inc.

TU-C-12A-09: Modeling Pathologic Response of Locally Advanced Esophageal Cancer to Chemo-Radiotherapy Using Quantitative PET/CT Features, Clinical Parameters and Demographics

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

Zhang, H; Chen, W; Kligerman, S

2014-06-15

Purpose: To develop predictive models using quantitative PET/CT features for the evaluation of tumor response to neoadjuvant chemo-radiotherapy (CRT) in patients with locally advanced esophageal cancer. Methods: This study included 20 patients who underwent tri-modality therapy (CRT + surgery) and had {sup 18}F-FDG PET/CT scans before initiation of CRT and 4-6 weeks after completion of CRT but prior to surgery. Four groups of tumor features were examined: (1) conventional PET/CT response measures (SUVmax, tumor diameter, etc.); (2) clinical parameters (TNM stage, histology, etc.) and demographics; (3) spatial-temporal PET features, which characterize tumor SUV intensity distribution, spatial patterns, geometry, and associatedmore » changes resulting from CRT; and (4) all features combined. An optimal feature set was identified with recursive feature selection and cross-validations. Support vector machine (SVM) and logistic regression (LR) models were constructed for prediction of pathologic tumor response to CRT, using cross-validations to avoid model over-fitting. Prediction accuracy was assessed via area under the receiver operating characteristic curve (AUC), and precision was evaluated via confidence intervals (CIs) of AUC. Results: When applied to the 4 groups of tumor features, the LR model achieved AUCs (95% CI) of 0.57 (0.10), 0.73 (0.07), 0.90 (0.06), and 0.90 (0.06). The SVM model achieved AUCs (95% CI) of 0.56 (0.07), 0.60 (0.06), 0.94 (0.02), and 1.00 (no misclassifications). Using spatial-temporal PET features combined with conventional PET/CT measures and clinical parameters, the SVM model achieved very high accuracy (AUC 1.00) and precision (no misclassifications), significantly better than using conventional PET/CT measures or clinical parameters and demographics alone. For groups with a large number of tumor features (groups 3 and 4), the SVM model achieved significantly higher accuracy than the LR model. Conclusion: The SVM model using all features including quantitative PET/CT features accurately and precisely predicted pathologic tumor response to CRT in esophageal cancer. This work was supported in part by National Cancer Institute Grant R21 CA131979 and R01 CA172638. Shan Tan was supported in part by the National Natural Science Foundation of China 60971112 and 61375018, and by Fundamental Research Funds for the Central Universities 2012QN086.« less

Pathological game use in adults with and without Autism Spectrum Disorder

PubMed Central

Engelhardt, Christopher R.

2017-01-01

This study tested whether adults with autism spectrum disorder (ASD) are at higher risk for pathological game use than typically developing (TD) adults. Participants included 119 adults with and without ASD. Participants completed measures assessing daily hours of video game use, percent of free time spent playing video games, and symptoms of pathological game use. The results indicated that adults with ASD endorsed more symptoms of video game pathology than did TD adults. This relationship was strong, enjoying 300,000-to-1 odds in Bayesian model comparison. Results also showed that adults with ASD spent more daily hours playing video games and spent a higher percent of their free time playing video games than did TD adults. Even after adjustment for these differences in daily video game hours and proportion of free time spent on games, model comparisons found evidence for a difference in game pathology scores associated with ASD status. Additionally, escapism motives for playing video games was associated with game pathology scores in both ASD and TD adults, replicating and extending a previous report. In conclusion, the risk for pathological game use appears larger in adults with ASD compared with TD adults. These findings point to pathological game use as a potentially important focus of clinical attention in adults with ASD. PMID:28663933

Pathological game use in adults with and without Autism Spectrum Disorder.

PubMed

Engelhardt, Christopher R; Mazurek, Micah O; Hilgard, Joseph

2017-01-01

This study tested whether adults with autism spectrum disorder (ASD) are at higher risk for pathological game use than typically developing (TD) adults. Participants included 119 adults with and without ASD. Participants completed measures assessing daily hours of video game use, percent of free time spent playing video games, and symptoms of pathological game use. The results indicated that adults with ASD endorsed more symptoms of video game pathology than did TD adults. This relationship was strong, enjoying 300,000-to-1 odds in Bayesian model comparison. Results also showed that adults with ASD spent more daily hours playing video games and spent a higher percent of their free time playing video games than did TD adults. Even after adjustment for these differences in daily video game hours and proportion of free time spent on games, model comparisons found evidence for a difference in game pathology scores associated with ASD status. Additionally, escapism motives for playing video games was associated with game pathology scores in both ASD and TD adults, replicating and extending a previous report. In conclusion, the risk for pathological game use appears larger in adults with ASD compared with TD adults. These findings point to pathological game use as a potentially important focus of clinical attention in adults with ASD.

Perfusion alterations converge with patterns of pathological spread in transactive response DNA-binding protein 43 proteinopathies.

PubMed

Ferraro, Pilar M; Jester, Charles; Olm, Christopher A; Placek, Katerina; Agosta, Federica; Elman, Lauren; McCluskey, Leo; Irwin, David J; Detre, John A; Filippi, Massimo; Grossman, Murray; McMillan, Corey T

2018-04-17

Amyotrophic lateral sclerosis (ALS) and the behavioral variant of frontotemporal dementia (bvFTD) commonly share the presence of transactive response DNA-binding protein 43 (TDP-43) inclusions. Structural magnetic resonance imaging studies demonstrated evidence for TDP-43 pathology spread, but while structural imaging usually reveals overt neuronal loss, perfusion imaging may detect more subtle neural activity alterations. We evaluated perfusion as an early marker for incipient pathology-associated brain alterations in TDP-43 proteinopathies. Cortical thickness (CT) and perfusion measurements were obtained in ALS (N = 18), pathologically and/or genetically confirmed bvFTD-TDP (N = 12), and healthy controls (N = 33). bvFTD showed reduced frontotemporal CT, hypoperfusion encompassing orbitofrontal and temporal cortices, and hyperperfusion in motor and occipital regions. ALS did not show reduced CT, but exhibited hypoperfusion in motor and temporal regions, and hyperperfusion in frontal and occipital cortices. Frontotemporal hypoperfusion and reduced CT correlated with cognitive and behavioral impairments as investigated using Mini-Mental State Examination and Philadelphia Brief Assessment of Cognition in bvFTD, and hypoperfusion in motor regions correlated with motor disability as measured by the ALS Functional Rating Scale-Revised in ALS. Hypoperfusion marked early pathologically involved regions, while hyperperfusion characterized regions of late pathological involvement. Distinct perfusion patterns may provide early markers of pathology distribution in TDP-43 proteinopathies. Copyright © 2018 Elsevier Inc. All rights reserved.

Effects of dual pathology on cognitive outcome following left anterior temporal lobectomy for treatment of epilepsy.

PubMed

Prayson, B E; Prayson, R A; Kubu, C S; Bingaman, W; Najm, I M; Busch, R M

2013-09-01

The objective of this retrospective study was to determine if dual pathology [DUAL - focal cortical dysplasia (FCD) and mesial temporal sclerosis (MTS)] in patients with left temporal lobe epilepsy is associated with greater risk for cognitive decline following temporal lobectomy than single pathology (MTS only). Sixty-three adults (Mage=36.5years, female: 52.4%) who underwent left anterior temporal lobectomy for treatment of epilepsy (MTS=28; DUAL=35) completed preoperative and postoperative neuropsychological evaluations. The base rate of dual pathology was 55.5%. Repeated measures ANOVAs yielded significant 2-way interactions (group×time) on most measures of language and memory with generally moderate effect sizes. Specifically, patients with MTS only demonstrated postoperative declines, while those with dual pathology remained unchanged or improved. Results suggest that dual pathology may be associated with better cognitive outcome following epilepsy surgery than MTS alone, possibly reflecting limited functionality of the resected tissue or intrahemispheric reorganization of function in the context of a developmental lesion. Copyright © 2013 Elsevier Inc. All rights reserved.

Cognitive distortions, anxiety, and depression among regular and pathological gambling online poker players.

PubMed

Barrault, Servane; Varescon, Isabelle

2013-03-01

The aims were to assess cognitive distortions and psychological distress (anxiety and depression) among online poker players of different levels of gambling intensity (non-pathological gamblers [NPG], problem gamblers [PbG], and pathological gamblers [PG]), and to examine the relationship between these variables and gambling pathology. Overall, 245 regular online poker players recruited on an Internet forum completed online self-report scales assessing pathological gambling (South Oaks Gambling Screen [SOGS]), psychological distress (Hospital Anxiety and Depression Scale [HADS]) and cognitive distortions (Gambling-Related Cognition Scale). Based on their SOGS scores, poker players were ranked into three groups: NPG (n=146), PbG (n=55), and PG (n=44). All poker players appeared to be more anxious than depressive. PG exhibited higher levels of depression and anxiety than did PbG and NPG. Cognitive distortions also significantly discriminated PG from PbG and NPG. A regression model showed that the perceived inability to stop gambling, the illusion of control, depression (HADS D), and anxiety were good predictors for pathological gambling among poker players. Our results suggest that cognitive distortions play an important role in the development and maintenance of gambling pathology. This study also underlines the role of anxiety and depression in pathological gambling among poker players. It seems relevant to take these elements into account in the research, prevention, and treatment of pathological gambling poker players.

The effect of three-monthly albendazole treatment on Th2 responses: Differential effects on IgE and IL-5.

PubMed

de Ruiter, K; Tahapary, D L; Wammes, L J; Wiria, A E; Hamid, F; van Lieshout, L; Smit, J W A; Houwing-Duistermaat, J J; Sartono, E; Supali, T; Yazdanbakhsh, M

2017-06-01

Helminth parasites induce a strong Th2 response, characterized by high levels of IgE and elevated signature cytokines such as IL-5. As many global deworming programmes are underway, there is concern that this might lead to emergence of Th1-mediated pathologies when the counterbalancing helminth-induced Th2 response is absent. Therefore, we assessed the effect of deworming on Th2-mediated responses in a household-clustered randomized controlled trial in Indonesia. Total plasma IgE and whole-blood IL-5 responses to mitogen phytohaemagglutinin (PHA) were measured in 1494 and 682 subjects, respectively, at baseline, 9 and 21 months after three-monthly single-dose treatment with albendazole or placebo. Anthelmintic treatment did not result in complete removal of helminth infections in the community. However, treatment significantly decreased IgE levels in albendazole- compared to placebo-treated subjects. IL-5 responses to PHA were not significantly affected by anthelmintic treatment and tended to increase in albendazole-treated subjects, indicating that intensive treatment of helminth parasites has different outcomes on B-cell (IgE levels) and T-cell (IL-5) responses. The data shows that 2 years of deworming can have differential effects on responses typified as Th2-mediated, which needs to be taken into account when examining the impact of helminths on noncommunicable diseases. © 2017 John Wiley & Sons Ltd.

Recirculant hyperthermic IntraVEsical chemotherapy (HIVEC) in intermediate-high-risk non-muscle-invasive bladder cancer.

PubMed

Sousa, Alejandro; Piñeiro, Idelfonso; Rodríguez, Silvia; Aparici, Vicente; Monserrat, Victor; Neira, Pilar; Carro, Enrique; Murias, Cármen; Uribarri, Carlos

2016-06-01

Purpose To examine the effectiveness of hyperthermic intravesical chemotherapy (HIVEC™) with mitomycin-C (MMC) for patients with intermediate-high-risk non-muscle invasive bladder cancer (NMIBC). Materials and methods From November 2010 to April 2015, 40 patients with intermediate-high-risk NMIBC received HIVEC™ treatment with a Combat BRS system. Of these patients, 24 received neoadjuvant HIVEC™ treatment (eight weekly instillations) before a transurethral resection of the bladder (TURBT) and 16 received adjuvant HIVEC™ treatment post-TURBT (four instillations weekly + six monthly). The pathological response of each tumour was evaluated after the neoadjuvant treatment. Recurrence rates and adverse effects were evaluated in both groups. Results A total of 40 patients completed the induction therapy: 24 patients received the Neoadjuvant HIVEC™ treatment. Of these patients, 15 (62.5%) showed a complete response. Eight patients (33.3%) showed a partial response, and one patient (4.1%) showed no response at all. The 4-year cumulative incidence of recurrence was 20.8%. The adjuvant HIVEC™ treatment was given to 16 patients. The 2-year cumulative incidence of recurrence was 12.5% for this group. The incidence and severity of side effects were slightly lower in the adjuvant group than in the neoadjuvant group. However, the difference was not statistically significant (p < 0.3). Most of the side effects were low grade and had virtually no effect on the treatment plan, and 97% of patients completed all of the HIVEC™ instillations scheduled. Conclusions The recirculation of hyperthermic MMC using Combat's HIVEC™ treatment is safe and effective and is capable of achieving good success rates in both neoadjuvant and adjuvant settings. This treatment seems to be appropriate for NMIBC intermediate-high-risk patients who cannot tolerate or have contraindications for standard BCG therapy or in cases in which there are supply issues or shortages of BCG.

Practice Patterns of Radiation Field Design for Sentinel Lymph Node-Positive Early-Stage Breast Cancer.

PubMed

Azghadi, Soheila; Daly, Megan; Mayadev, Jyoti

2016-10-01

Recent randomized trials have led to decreased use of completion axillary lymph node dissection (ALND) in early-stage breast cancer patients with a positive sentinel lymph node (SLN), causing controversy surrounding radiotherapy coverage of the axilla. We investigated the practice variation among radiation oncologists for regional nodal coverage for clinicopathologic scenarios and evaluated axillary field design decision-making processes. A customized, web-based questionnaire was e-mailed to 983 community (n = 617) and academic (n = 366) radiation oncologists with a breast cancer subspecialty practicing in the United States. The survey consisted of 18 multiple-choice questions evaluating general clinical preferences surrounding radiation therapy (RT) field design for patients with early-stage breast cancer and a positive SLN. Seven case scenarios were developed to investigate the field design in the setting of specific clinical and pathologic risk factors. Nodal coverage was classified as standard tangents (STs), high tangents (HTs), STs and a supraclavicular field (SCF), or STs and full axillary coverage (AX). A total of 145 evaluable responses were collected, with a response rate of 15.0%. Of the respondents, 12 (8.3%) reported using completion ALND for patients with 1 to 3 positive SLNs without extracapsular extension (ECE) and 66 (45.5%) performed ALND with 1 to 3 positive SLNs with ECE. For micrometastatic SLNs, with no lymphovascular system invasion, 115 (87.1%) used STs or HTs. The use of neoadjuvant chemotherapy (NAC) influenced RT field design for patients with a positive SLN without ECE, with 64 (48.5%) using STs and SCF or STs and AX treatment without NAC and 94 (70.7%) using SCF and AX after NAC. With macrometastatic SLN involvement, most respondents preferred SCF (45.27%) and AX (45.66%). In contrast, for micrometastatic involvement, HTs (43.61%) were frequently chosen. Forty (27.8%) reported using online predictive nomograms to predict further axillary involvement, with no difference between the academic and community radiation oncologists (P = .11). In SLN biopsy-positive early-stage breast cancer with omission of completion ALND, axillary RT is increasing used to cover the undissected axilla. Most respondents use SCF or AX for patients with low to intermediate pathologic features. Online prediction nomograms are used by a few practitioners to assist in clinical decision-making in this setting. Copyright © 2016 Elsevier Inc. All rights reserved.

Toxicologic Pathology: The Basic Building Block of Risk Assessment

EPA Science Inventory

Human health risk assessment is a critical factor in many risk management decisions. Evaluation of human health risk requires research the provides information that appropriately characterizes potential hazards from exposure. Pathology endpoints are the central response around ...

Role reversal method for treatment of food refusal associated with infantile feeding disorders.

PubMed

Segal, Idit; Tirosh, Anat; Sinai, Tali; Alony, Sari; Levi, Anat; Korenfeld, Lia; Zangen, Tsili; Mizrachi, Avi; Boaz, Mona; Levine, Arie

2014-06-01

Infantile feeding disorders (IFDs) are common causes of food refusal and failure to thrive, and are frequently encountered by primary care physicians and specialists. We have published the Wolfson criteria for IFD, which have eased the approach to the diagnosis of IFDs. Along with and complementary to the Wolfson criteria, we have also developed the role reversal treatment method for IFD, which has been briefly described earlier. The aim of this study was to validate the role reversal treatment method on a cohort of infants diagnosed as having IFD and to present a detailed description of this method for the first time. Parents of infants and children diagnosed as having IFD were invited to participate in the study; they were handed over a questionnaire comprising 6 categories of questions related to patient and parents behaviors, attitudes, and perceptions, which was completed at initiation and at the end of treatment. Full response was defined as improved normative feeding, cessation of abnormal parental feeding, and improved or normal growth patterns. A partial response was defined as success with two-third categories. We enrolled 38 patients, and 32 patients completed the study. Improved feeding occurred in 78%, full recovery was documented in 53% of infants by 6 months, and partial response was observed in another 25%. All forms of pathological feeding improved significantly (mechanistic, nocturnal, persecutory, forced feeding, and distraction). The role reversal treatment method is a simple and effective approach to the treatment of food refusal associated with IFD.

MiRNA Expression Analysis of Pretreatment Biopsies Predicts the Pathological Response of Esophageal Squamous Cell Carcinomas to Neoadjuvant Chemoradiotherapy.

PubMed

Wen, Jing; Luo, Kongjia; Liu, Hui; Liu, Shiliang; Lin, Guangrong; Hu, Yi; Zhang, Xu; Wang, Geng; Chen, Yuping; Chen, Zhijian; Li, Yi; Lin, Ting; Xie, Xiuying; Liu, Mengzhong; Wang, Huiyun; Yang, Hong; Fu, Jianhua

2016-05-01

To identify miRNA markers useful for esophageal squamous cell carcinoma (ESCC) neoadjuvant chemoradiotherapy (neo-CRT) response prediction. Neo-CRT followed by surgery improves ESCC patients' survival compared with surgery alone. However, CRT outcomes are heterogeneous, and no current methods can predict CRT responses. Differentially expressed miRNAs between ESCC pathological responders and nonresponders after neo-CRT were identified by miRNA profiling and verified by real-time quantitative polymerase chain reaction (qPCR) of 27 ESCCs in the training set. Several class prediction algorithms were used to build the response-classifying models with the qPCR data. Predictive powers of the models were further assessed with a second set of 79 ESCCs. Ten miRNAs with greater than a 1.5-fold change between pathological responders and nonresponders were identified and verified, respectively. A support vector machine (SVM) prediction model, composed of 4 miRNAs (miR-145-5p, miR-152, miR-193b-3p, and miR-376a-3p), were developed. It provided overall accuracies of 100% and 87.3% for discriminating pathological responders and nonresponders in the training and external validation sets, respectively. In multivariate analysis, the subgroup determined by the SVM model was the only independent factor significantly associated with neo-CRT response in the external validation sets. Combined qPCR of the 4 miRNAs provides the possibility of ESCC neo-CRT response prediction, which may facilitate individualized ESCC treatment. Further prospective validation in larger independent cohorts is necessary to fully assess its predictive power.

Immunotherapy of tuberculosis with Mycobacterium leprae Hsp65 as a DNA vaccine triggers cross-reactive antibodies against mammalian Hsp60 but not pathological autoimmunity

PubMed Central

Doimo, Nayara TS; Zárate-Bladés, Carlos R; Rodrigues, Rodrigo F; Tefé-Silva, Cristiane; Trotte, Marcele NS; Souza, Patrícia RM; Soares, Luana S; Rios, Wendy M; Floriano, Elaine M; Brandão, Izaira T; Masson, Ana P; Coelho, Verônica; Ramos, Simone G; Silva, Celio L

2014-01-01

Despite substantial efforts in recent years toward the development of new vaccines and drugs against tuberculosis (TB), success has remained elusive. Immunotherapy of TB with mycobacterial Hsp65 as a DNA vaccine (DNA-hsp65) results in a reduction of systemic bacterial loads and lung tissue damage, but the high homology of Hsp65 with the mammalian protein raises concern that pathological autoimmune responses may also be triggered. We searched for autoimmune responses elicited by DNA-hsp65 immunotherapy in mice chronically infected with TB by evaluating the humoral immune response and comprehensive histopathology using stereology. Cross-reactive antibodies between mycobacterial and mammalian Hsp60/65 were detected; however, no signs of pathological autoimmunity were found up to 60 days after the end of the therapy. PMID:24607935

Eating pathology in East African women: the role of media exposure and globalization.

PubMed

Eddy, Kamryn T; Hennessey, Moira; Thompson-Brenner, Heather

2007-03-01

Eating disorder (ED) pathology and its relation to media exposure and globalization were assessed in a sample of young Tanzanian females (N = 214; 19.4 years +/- 3.8 years). Participants completed Kiswahili versions of a DSM-IV ED symptom clinical interview, the Eating Disorder Inventory (EDI), and a media exposure/globalization questionnaire. One third endorsed cognitive ED symptoms; bingeing (10%) and purging (5%) were less common. Four women (1.9%) met modified criteria for anorexia nervosa, one for bulimia nervosa, and 10 (4.7%) reported clinically significant ED pathology consistent with an ED not otherwise specified diagnosis. Media exposure and Western exposure (e.g., travel abroad) were positively associated with ED symptoms. The intended factor structure of the EDI was not supported. Eating pathology is present in this developing nation and is most common in subpopulations with increased exposure to Western culture. Future research should replicate these findings to clarify the role of Western media in the development of ED pathology.

Eating disorder symptomatology among ballet dancers.

PubMed

Ringham, Rebecca; Klump, Kelly; Kaye, Walter; Stone, David; Libman, Steven; Stowe, Susan; Marcus, Marsha

2006-09-01

The current study sought to compare eating disorder symptomatology among ballet dancers and individuals with restricting anorexia nervosa (RAN), bulimia nervosa (BN), and no eating pathology. Twenty-nine female ballet dancers completed assessments and were compared with an archival dataset of 26 women with RAN, 47 women with BN, and 44 women with no eating pathology. Eating disorder diagnoses and behaviors were assessed with a semi-structured clinical interview, the Eating Disorder Inventory (EDI), and a weight history interview. Eighty-three percent of dancers met lifetime criteria for AN (6.9%), BN (10.3%), AN+BN (10.3%), or EDNOS (55.0%). Moreover, dancers looked more similar to eating-disordered individuals than to control individuals on measures of eating pathology. Despite previous emphasis on the pathology AN, the current findings suggest that dancers frequently engage in binge eating and purging behaviors. Moreover, it appears that their pathology is as severe as that of non-dancing women with eating disorders. Copyright (c) 2006 by Wiley Periodicals, Inc.

[Pathology websites in the World Wide Web. A guide for a specific research of pathology information on the Internet].

PubMed

Böhm, J

2008-05-01

Being a global information network, the internet has becoming increasingly important for pathologists as a medium for professional communication and information. Although a large number of pathology-specific websites (PSWs) are accessible on the internet, the potentials of PSWs are still barely known. Since there is no global catalog for all the pathology websites, certain PSWs are difficult to find on the internet. PSWs offer lavishly illustrated education material for undergraduates and postgraduates in pathology, but may also be very useful as reference books or as an instrument of continuing medical education (CME) for experienced pathologists. The spectrum of PSW media comprises electronic training manuals, journals, case collections, photo-archives, and even complete section series of virtual microscopy. PSWs are available at any time, can be updated permanently and linked to further online sources of information. We demonstrate how to find PSWs and present an annotated list of some 100 of the best PSWs.

Voice problems of group fitness instructors: diagnosis, treatment, perceived and experienced attitudes and expectations of the industry.

PubMed

Rumbach, Anna F

2013-11-01

To determine the anatomical and physiological nature of voice problems and their treatment in those group fitness instructors (GFIs) who have sought a medical diagnosis; the impact of voice disorders on quality of life and their contribution to activity limitations and participation restrictions; and the perceived attitudes and level of support from the industry at large in response to instructor's voice disorders and need for treatment. Prospective self-completion questionnaire design. Thirty-eight individuals (3 males and 35 females) currently active in the Australian fitness industry who had been diagnosed with a voice disorder completed an online self-completion questionnaire administered via SurveyMonkey. Laryngeal pathology included vocal fold nodules (N = 24), vocal fold cysts (N = 2), vocal fold hemorrhage (N = 1), and recurrent chronic laryngitis (N = 3). Eight individuals reported vocal strain and muscle tension dysphonia without concurrent vocal fold pathology. Treatment methods were variable, with 73.68% (N = 28) receiving voice therapy alone, 7.89% (N = 3) having voice therapy in combination with surgery, and 10.53% (N = 4) having voice therapy in conjunction with medication. Three individuals (7.89%) received no treatment for their voice disorder. During treatment, 82% of the cohort altered their teaching practices. Half of the cohort reported that their voice problems led to social withdrawal, decreased job satisfaction, and emotional distress. Greater than 65% also reported being dissatisfied with the level of industry and coworker support during the period of voice recovery. This study identifies that GFIs are susceptible to a number of voice disorders that impact their social and professional lives, and there is a need for more proactive training and advice on voice care for instructors, as well as those in management positions within the industry to address mixed approaches and opinions regarding the importance of voice care. Copyright © 2013 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

Inference of tumor evolution during chemotherapy by computational modeling and in situ analysis of genetic and phenotypic cellular diversity.

PubMed

Almendro, Vanessa; Cheng, Yu-Kang; Randles, Amanda; Itzkovitz, Shalev; Marusyk, Andriy; Ametller, Elisabet; Gonzalez-Farre, Xavier; Muñoz, Montse; Russnes, Hege G; Helland, Aslaug; Rye, Inga H; Borresen-Dale, Anne-Lise; Maruyama, Reo; van Oudenaarden, Alexander; Dowsett, Mitchell; Jones, Robin L; Reis-Filho, Jorge; Gascon, Pere; Gönen, Mithat; Michor, Franziska; Polyak, Kornelia

2014-02-13

Cancer therapy exerts a strong selection pressure that shapes tumor evolution, yet our knowledge of how tumors change during treatment is limited. Here, we report the analysis of cellular heterogeneity for genetic and phenotypic features and their spatial distribution in breast tumors pre- and post-neoadjuvant chemotherapy. We found that intratumor genetic diversity was tumor-subtype specific, and it did not change during treatment in tumors with partial or no response. However, lower pretreatment genetic diversity was significantly associated with pathologic complete response. In contrast, phenotypic diversity was different between pre- and posttreatment samples. We also observed significant changes in the spatial distribution of cells with distinct genetic and phenotypic features. We used these experimental data to develop a stochastic computational model to infer tumor growth patterns and evolutionary dynamics. Our results highlight the importance of integrated analysis of genotypes and phenotypes of single cells in intact tissues to predict tumor evolution. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Inference of tumor evolution during chemotherapy by computational modeling and in situ analysis of cellular diversity for genetic and phenotypic features

PubMed Central

Almendro, Vanessa; Cheng, Yu-Kang; Randles, Amanda; Itzkovitz, Shalev; Marusyk, Andriy; Ametller, Elisabet; Gonzalez-Farre, Xavier; Muñoz, Montse; Russnes, Hege G.; Helland, Åslaug; Rye, Inga H.; Borresen-Dale, Anne-Lise; Maruyama, Reo; van Oudenaarden, Alexander; Dowsett, Mitchell; Jones, Robin L.; Reis-Filho, Jorge; Gascon, Pere; Gönen, Mithat; Michor, Franziska; Polyak, Kornelia

2014-01-01

SUMMARY Cancer therapy exerts a strong selection pressure that shapes tumor evolution, yet our knowledge of how tumors change during treatment is limited. Here we report the analysis of cellular heterogeneity for genetic and phenotypic features and their spatial distribution in breast tumors pre- and post-neoadjuvant chemotherapy. We found that intratumor genetic diversity was tumor subtype-specific and it did not change during treatment in tumors with partial or no response. However, lower pre-treatment genetic diversity was significantly associated with complete pathologic response. In contrast, phenotypic diversity was different between pre- and post-treatment samples. We also observed significant changes in the spatial distribution of cells with distinct genetic and phenotypic features. We used these experimental data to develop a stochastic computational model to infer tumor growth patterns and evolutionary dynamics. Our results highlight the importance of integrated analysis of genotypes and phenotypes of single cells in intact tissues to predict tumor evolution. PMID:24462293

Inference of tumor evolution during chemotherapy by computational modeling and in situ analysis of genetic and phenotypic cellular diversity

DOE PAGES

Almendro, Vanessa; Cheng, Yu -Kang; Randles, Amanda; ...

2014-02-01

Cancer therapy exerts a strong selection pressure that shapes tumor evolution, yet our knowledge of how tumors change during treatment is limited. Here, we report the analysis of cellular heterogeneity for genetic and phenotypic features and their spatial distribution in breast tumors pre- and post-neoadjuvant chemotherapy. We found that intratumor genetic diversity was tumor-subtype specific, and it did not change during treatment in tumors with partial or no response. However, lower pretreatment genetic diversity was significantly associated with pathologic complete response. In contrast, phenotypic diversity was different between pre- and post-treatment samples. We also observed significant changes in the spatialmore » distribution of cells with distinct genetic and phenotypic features. We used these experimental data to develop a stochastic computational model to infer tumor growth patterns and evolutionary dynamics. Our results highlight the importance of integrated analysis of genotypes and phenotypes of single cells in intact tissues to predict tumor evolution.« less

Association of ABCB1 and ABCG2 single nucleotide polymorphisms with clinical findings and response to chemotherapy treatments in Kurdish patients with breast cancer.

PubMed

Ghafouri, Houshiyar; Ghaderi, Bayazid; Amini, Sabrieh; Nikkhoo, Bahram; Abdi, Mohammad; Hoseini, Abdolhakim

2016-06-01

The possible interaction between gene polymorphisms and risk of cancer progression is very interesting. Polymorphisms in multi-drug resistance genes have an important role in response to anti-cancer drugs. The present study was aimed to evaluate the possible effects of ABCB1 C3435T and ABCG2 C421A single nucleotide polymorphisms on clinical and pathological outcomes of Kurdish patients with breast cancer. One hundred breast cancer patients and 200 healthy controls were enrolled in this case-control study. Clinical and pathological findings of all individuals were reported, and immunohistochemistry staining was used to assess the tissue expression of specific breast cancer proteins. The ABCB1 C3435T and ABCG2 C421 genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP). The distribution of different genotypes between patient and control groups was only significant for ABCG2 C421A. A allele of ABCG2 C421A polymorphisms were significantly higher in patients than in controls. Patients with AA genotype of ABCG2 C421A were at higher risk of progressing breast cancer. Patients with A allele of ABCG2 had complete response to chemotherapeutic agents. There was no statistically significant association between ABCB1 C3435T and ABCG2 C421A polymorphisms and tissue expression of ER, PR, Her2/neu, and Ki67. The ABCB1 C3435T has no correlation with clinical findings and treatment with chemotherapy drugs. The A allele of ABCG2 C421A may be a risk factor for progression of breast cancer in Kurdish patients. In addition, breast cancer patients with C allele of this polymorphism have weaker response to treatments with anthracyclines and Paclitaxol.

DNA Mismatch Repair Deficiency in Rectal Cancer: Benchmarking Its Impact on Prognosis, Neoadjuvant Response Prediction, and Clinical Cancer Genetics

PubMed Central

de Rosa, Nicole; Rodriguez-Bigas, Miguel A.; Chang, George J.; Veerapong, Jula; Borras, Ester; Krishnan, Sunil; Bednarski, Brian; Messick, Craig A.; Skibber, John M.; Feig, Barry W.; Lynch, Patrick M.; Vilar, Eduardo

2016-01-01

Purpose DNA mismatch repair deficiency (dMMR) hallmarks consensus molecular subtype 1 of colorectal cancer. It is being routinely tested, but little is known about dMMR rectal cancers. The efficacy of novel treatment strategies cannot be established without benchmarking the outcomes of dMMR rectal cancer with current therapy. We aimed to delineate the impact of dMMR on prognosis, the predicted response to fluoropyrimidine-based neoadjuvant therapy, and implications of germline alterations in the MMR genes in rectal cancer. Methods Between 1992 and 2012, 62 patients with dMMR rectal cancers underwent multimodality therapy. Oncologic treatment and outcomes as well as clinical genetics work-up were examined. Overall and rectal cancer–specific survival were calculated by the Kaplan-Meier method. Results The median age at diagnosis was 41 years. MMR deficiency was most commonly due to alterations in MSH2 (53%) or MSH6 (23%). After a median follow-up of 6.8 years, the 5-year rectal cancer–specific survival was 100% for stage I and II, 85.1% for stage III, and 60.0% for stage IV disease. Fluoropyrimidine-based neoadjuvant chemoradiation was associated with a complete pathologic response rate of 27.6%. The extent of surgical resection was influenced by synchronous colonic disease at presentation, tumor height, clinical stage, and pelvic radiation. An informed decision for a limited resection focusing on proctectomy did not compromise overall survival. Five of the 11 (45.5%) deaths during follow-up were due to extracolorectal malignancies. Conclusion dMMR rectal cancer had excellent prognosis and pathologic response with current multimodality therapy including an individualized surgical treatment plan. Identification of a dMMR rectal cancer should trigger germline testing, followed by lifelong surveillance for both colorectal and extracolorectal malignancies. We herein provide genotype-specific outcome benchmarks for comparison with novel interventions. PMID:27432916

Maladaptive eating behavior assessment among bariatric surgery candidates: Evaluation of the Eating Disorder Diagnostic Scale.

PubMed

Williams, Gail A; Hawkins, Misty A W; Duncan, Jennifer; Rummell, Christina M; Perkins, Shannon; Crowther, Janis H

2017-07-01

Eating pathology among bariatric surgery candidates is common and associated with adverse outcomes. However, its assessment is complicated by the inconsistent use of standardized measures. We addressed this by examining the use of the Eating Disorder Diagnostic Scale (EDDS) in a large bariatric sample (N = 343). To evaluate the EDDS among bariatric surgery candidates via examination of: (1) Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision (DSM-IV-TR) and fifth edition (DSM-5) rates of binge eating disorder, bulimia nervosa, and maladaptive eating behaviors, and (2) the relationship between response biases and self-reported eating disorder symptoms. Participants were bariatric surgery candidates at a large public hospital in the Midwest. As part of a larger preoperative evaluation, 343 patients seeking bariatric surgery completed the EDDS and measures of problematic response bias. Approximately 16% of the sample met full threshold criteria for binge eating disorder using DSM-5 criteria. Using the DSM-IV-TR, rates were lower but still substantial at 13%. Rates for bulimia nervosa were 8% (DSM-5) and 6% (DSM-IV-TR). The majority (66.1%) of participants reported at least one binge-eating episode per week. The most commonly used compensatory behavior was fasting (20.4%), followed by excessive exercise (11.7%), laxative use (5.6%), and vomiting (1.8%). An inverse relationship between severity of the eating symptomatology and problematic response bias emerged. The EDDS shows promise as a screening tool that uses diagnostic criteria to provide rates of binge eating and eating psychopathology among surgical candidates. Our findings suggest that subsequent validation studies of this measure are needed, should address potential response bias concerns, and should employ clear definitions of binge eating to promote standardization of eating pathology assessment in the bariatric population. Copyright © 2017 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

Effect of long interval between hyperthermochemoradiation therapy and surgery for rectal cancer on apoptosis, proliferation and tumor response.

PubMed

Kato, Toshihide; Fujii, Takaaki; Ide, Munenori; Takada, Takahiro; Sutoh, Toshinaga; Morita, Hiroki; Yajima, Reina; Yamaguchi, Satoru; Tsutsumi, Soichi; Asao, Takayuki; Oyama, Tetsunari; Kuwano, Hiroyuki

2014-06-01

Neoadjuvant chemoradiotherapy is commonly used to improve the local control and resectability of locally advanced rectal cancer, with surgery performed after an interval of a number of weeks. We have been conducting a clinical trial of preoperative chemoradiotherapy in combination with regional hyperthermia (hyperthermo-chemoradiation therapy; HCRT) for locally advanced rectal cancer. In the current study we assessed the effect of a longer (>10 weeks) interval after neoadjuvant HCRT on pathological response, oncological outcome and especially on apoptosis, proliferation and p53 expression in patients with rectal cancer. Forty-eight patients with proven rectal adenocarcinoma who underwent HCRT followed by surgery were identified for inclusion in this study. Patients were divided into two groups according to the interval between HCRT and surgery, ≤ 10 weeks (short-interval group) and >10 weeks (long-interval group). Patients in the long-interval group had a significantly higher rate of pathological complete response (pCR) (43.5% vs. 16.0%) than patients of the short-interval group. Patients of the long-interval group had a significantly higher rate of down-staging of T-stage (78.3% vs. 36.0%) and relatively higher rate of that of N-stage (52.2% vs. 36.0%) than patients of the short-interval group. Furthermore, apoptosis in the long-interval group was relatively higher compared to that of the short-interval group, without a significant difference in the Ki-67 proliferative index and expression of p53 in the primary tumor. In conclusion, we demonstrated that a longer interval after HCRT (>10 weeks) seemed to result in a better chance of a pCR, a result confirmed by the trends in tumor response markers, including apoptosis, proliferation and p53 expression. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

DNA Mismatch Repair Deficiency in Rectal Cancer: Benchmarking Its Impact on Prognosis, Neoadjuvant Response Prediction, and Clinical Cancer Genetics.

PubMed

de Rosa, Nicole; Rodriguez-Bigas, Miguel A; Chang, George J; Veerapong, Jula; Borras, Ester; Krishnan, Sunil; Bednarski, Brian; Messick, Craig A; Skibber, John M; Feig, Barry W; Lynch, Patrick M; Vilar, Eduardo; You, Y Nancy

2016-09-01

DNA mismatch repair deficiency (dMMR) hallmarks consensus molecular subtype 1 of colorectal cancer. It is being routinely tested, but little is known about dMMR rectal cancers. The efficacy of novel treatment strategies cannot be established without benchmarking the outcomes of dMMR rectal cancer with current therapy. We aimed to delineate the impact of dMMR on prognosis, the predicted response to fluoropyrimidine-based neoadjuvant therapy, and implications of germline alterations in the MMR genes in rectal cancer. Between 1992 and 2012, 62 patients with dMMR rectal cancers underwent multimodality therapy. Oncologic treatment and outcomes as well as clinical genetics work-up were examined. Overall and rectal cancer-specific survival were calculated by the Kaplan-Meier method. The median age at diagnosis was 41 years. MMR deficiency was most commonly due to alterations in MSH2 (53%) or MSH6 (23%). After a median follow-up of 6.8 years, the 5-year rectal cancer-specific survival was 100% for stage I and II, 85.1% for stage III, and 60.0% for stage IV disease. Fluoropyrimidine-based neoadjuvant chemoradiation was associated with a complete pathologic response rate of 27.6%. The extent of surgical resection was influenced by synchronous colonic disease at presentation, tumor height, clinical stage, and pelvic radiation. An informed decision for a limited resection focusing on proctectomy did not compromise overall survival. Five of the 11 (45.5%) deaths during follow-up were due to extracolorectal malignancies. dMMR rectal cancer had excellent prognosis and pathologic response with current multimodality therapy including an individualized surgical treatment plan. Identification of a dMMR rectal cancer should trigger germline testing, followed by lifelong surveillance for both colorectal and extracolorectal malignancies. We herein provide genotype-specific outcome benchmarks for comparison with novel interventions. © 2016 by American Society of Clinical Oncology.

TDP-43 stage, mixed pathologies, and clinical Alzheimer’s-type dementia

PubMed Central

James, Bryan D.; Wilson, Robert S.; Boyle, Patricia A.; Trojanowski, John Q.; Bennett, David A.; Schneider, Julie A.

2016-01-01

Hyperphosphorylated transactive response DNA-binding protein 43 (TDP-43, encoded by TARDBP) proteinopathy has recently been described in ageing and in association with cognitive impairment, especially in the context of Alzheimer’s disease pathology. To explore the role of mixed Alzheimer’s disease and TDP-43 pathologies in clinical Alzheimer’s-type dementia, we performed a comprehensive investigation of TDP-43, mixed pathologies, and clinical Alzheimer’s-type dementia in a large cohort of community-dwelling older subjects. We tested the hypotheses that TDP-43 with Alzheimer’s disease pathology is a common mixed pathology; is related to increased likelihood of expressing clinical Alzheimer’s-type dementia; and that TDP-43 pathologic stage is an important determinant of clinical Alzheimer’s-type dementia. Data came from 946 older adults with (n = 398) and without dementia (n = 548) from the Rush Memory and Aging Project and Religious Orders Study. TDP-43 proteinopathy (cytoplasmic inclusions) was present in 496 (52%) subjects, and the pattern of deposition was classified as stage 0 (none; 48%), stage 1 (amygdala; 18%), stage 2 (extension to hippocampus/entorhinal; 21%), or stage 3 (extension to neocortex; 14%). TDP-43 pathology combined with a pathologic diagnosis of Alzheimer’s disease was a common mixed pathology (37% of all participants), and the proportion of subjects with clinical Alzheimer’s-type dementia formerly labelled ‘pure pathologic diagnosis of Alzheimer’s disease’ was halved when TDP-43 was considered. In logistic regression models adjusted for age, sex, and education, TDP-43 pathology was associated with clinical Alzheimer’s-type dementia (odds ratio = 1.51, 95% confidence interval = 1.11, 2.05) independent of pathological Alzheimer’s disease (odds ratio = 4.30, 95% confidence interval = 3.08, 6.01) or other pathologies (infarcts, arteriolosclerosis, Lewy bodies, and hippocampal sclerosis). Mixed Alzheimer’s disease and TDP-43 pathologies were associated with higher odds of clinical Alzheimer’s-type dementia (odds ratio = 6.73, 95% confidence interval = 4.18, 10.85) than pathologic Alzheimer’s disease alone (odds ratio = 4.62, 95% confidence interval = 2.84, 7.52). In models examining TDP-43 stage, a dose-response relationship with clinical Alzheimer’s-type dementia was observed, and a significant association was observed starting at stage 2, extension beyond the amygdala. In this large sample from almost 1000 community participants, we observed that TDP-43 proteinopathy was very common, frequently mixed with pathological Alzheimer’s disease, and associated with a higher likelihood of the clinical expression of clinical Alzheimer’s-type dementia but only when extended beyond the amygdala. PMID:27694152

Hematopoietic responses under protracted exposures to low daily dose gamma irradiation

NASA Astrophysics Data System (ADS)

Seed, T. M.; Fritz, T. E.; Tolle, D. V.; Jackson, W. E.

In attempting to evaluate the possible health consequences of chronic ionizing radiation exposure during extended space travel (e.g., Mars Mission), ground-based experimental studies of the clinical and pathological responses of canines under low daily doses of 60Co gamma irradiation (0.3-26.3 cGy d -1) have been examined. Specific reference was given to responses of the blood forming system. Results suggest that the daily dose rate of 7.5 cGy d -1 represents a threshold below which the hematopoietic system can retain either partial or full trilineal cell-producing capacity (erythropoiesis, myelopoiesis, and megakaryopoiesis) for extended periods of exposure (> 1yr). Trilineal capacity was fully retained for several years of exposure at the lowest dose-rate tested (0.3 cGy d -1) but was completely lost within several hundred days at the highest dose-rate (26.3 cGy d -1). Retention of hematopoietic capacity under chronic exposure has been demonstrated to be mediated by hematopoietic progenitors with acquired radioresistance and repair functions, altered cytogenetics, and cell-cycle characteristics. Radiological, biological, and temporal parameters responsible for these vital acquisitions by hematopoietic progenitors have been partially characterized. These parameters, along with threshold responses, are described and discussed in relation to potential health risks of the space traveler under chronic stress of low-dose irradiation.

38 CFR 4.87a - Schedule of ratings-other sense organs.

Code of Federal Regulations, 2010 CFR

2010-07-01

... ratings—other sense organs. Rating 6275Sense of smell, complete loss 10 6276Sense of taste, complete loss 10 Note: Evaluation will be assigned under diagnostic codes 6275 or 6276 only if there is an anatomical or pathological basis for the condition. (Authority: 38 U.S.C. 1155) [64 FR 25210, May 11, 1999...

Type 2 responses at the interface between immunity and fat metabolism.

PubMed

Odegaard, Justin I; Chawla, Ajay

2015-10-01

Adipose tissue resident leukocytes are often cast solely as the effectors of obesity and its attendant pathologies; however, recent observations have demonstrated that these cells support and effect 'healthy' physiologic function as well as pathologic dysfunction. Importantly, these two disparate outcomes are underpinned by similarly disparate immune programs; type 2 responses instruct and promote metabolic normalcy, while type 1 responses drive tissue dysfunction. In this Review, we summarize the literature regarding type 2 immunity's role in adipose tissue physiology and allude to its potential therapeutic implications. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Personality Inventory for DSM-5 Short Form (PID-5-SF): psychometric properties and association with big five traits and pathological beliefs in a Norwegian population.

PubMed

Thimm, Jens C; Jordan, Stian; Bach, Bo

2016-12-07

With the publication of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), an alternative model for personality disorders based on personality dysfunction and pathological personality traits was introduced. The Personality Inventory for DSM-5 (PID-5) is a 220-item self-report inventory designed to assess the personality traits of this model. Recently, a short 100-item version of the PID-5 (PID-5-SF) has been developed. The aim of this study was to investigate the score reliability and structure of the Norwegian PID-5-SF. Further, criterion validity with the five factor model of personality (FFM) and pathological personality beliefs was examined. A derivation sample of university students (N = 503) completed the PID-5, the Big Five Inventory (BFI), and the Personality Beliefs Questionnaire - Short Form (PBQ-SF), whereas a replication sample of 127 students completed the PID-5-SF along with the aforementioned measures. The short PID-5 showed overall good score reliability and structural validity. The associations with FFM traits and pathological personality beliefs were conceptually coherent and similar for the two forms of the PID-5. The results suggest that the Norwegian PID-5 short form is a reliable and efficient measure of the trait criterion of the alternative model for personality disorders in DSM-5.

Discovery of pathologies by orthodontists on lateral cephalograms.

PubMed

Moffitt, Allen Hall

2011-01-01

To determine the frequency of significant pathologies on lateral cephalograms discovered by orthodontists during their careers. A five-statement survey was sent to the 417 active and affiliate members of the Edward H. Angle Society of Orthodontists. The survey asked orthodontists to identify any significant radiographic pathology that they had discovered on lateral cephalograms during their careers to date. The data were analyzed statistically. Of the 417 surveys, 201 were returned for a 48% response rate. Ninety-nine respondents or 49.3% of the sample had discovered at least one significant pathology. Of the 1.3 million patients observed by the orthodontists in the sample, 268 patients (0.02%) with significant pathologies had been identified. Younger orthodontists had a statistically greater potential to discover pathologies than older orthodontists. The general types of pathologies discovered were musculoskeletal (38%), glandular (28%), and dental groups (12%). About 50% of orthodontists will likely discover a significant, potentially life-affecting pathology on a lateral cephalogram.

Pathological narcissism and somatic symptoms among men and women attending an outpatient mental health clinic.

PubMed

Kealy, David; Tsai, Michelle; Ogrodniczuk, John S

2016-09-01

To explore the relationship between types of pathological narcissism and somatic symptoms among psychiatric outpatients. Patients (N = 95) completed measures of somatic symptoms, narcissistic grandiosity and vulnerability, and psychiatric symptoms. Relationships among variables were analysed using t-tests and correlations, controlling for psychiatric distress. Somatic symptoms were positively associated with two types of narcissistic dysfunction. Among women there was a positive association between somatic symptoms and narcissistic vulnerability, but not grandiosity. Among men, somatic symptoms were positively associated with narcissistic grandiosity, but not vulnerability. The connection between narcissistic pathology and somatic symptom severity appears to differ based on gender. Further research is needed to confirm and extend this preliminary finding.

The role of animal models in tendon research

PubMed Central

Hast, M. W.; Zuskov, A.; Soslowsky, L. J.

2014-01-01

Tendinopathy is a debilitating musculoskeletal condition which can cause significant pain and lead to complete rupture of the tendon, which often requires surgical repair. Due in part to the large spectrum of tendon pathologies, these disorders continue to be a clinical challenge. Animal models are often used in this field of research as they offer an attractive framework to examine the cascade of processes that occur throughout both tendon pathology and repair. This review discusses the structural, mechanical, and biological changes that occur throughout tendon pathology in animal models, as well as strategies for the improvement of tendon healing. Cite this article: Bone Joint Res 2014;3:193–202. PMID:24958818

Neurological soft signs in individuals with pathological gambling.

PubMed

Elman, Igor; Gurvits, Tamara V; Tschibelu, Evelyne; Spring, Justin D; Lasko, Natasha B; Pitman, Roger K

2013-01-01

Increased neurological soft signs (NSSs) have been found in a number of neuropsychiatric syndromes, including chemical addiction. The present study examined NSSs related to perceptual-motor and visuospatial processing in a behavioral addiction viz., pathological gambling (PG). As compared to mentally healthy individuals, pathological gamblers displayed significantly poorer ability to copy two- and three-dimensional figures, to recognize objects against a background noise, and to orient in space on a road-map test. Results indicated that PG is associated with subtle cerebral cortical abnormalities. Further prospective clinical research is needed to address the NSSs' origin and chronology (e.g., predate or follow the development of PG) as well as their response to therapeutic interventions and/or their ability to predict such a response.

Endoplasmic Reticulum Stress in Arterial Smooth Muscle Cells: A Novel Regulator of Vascular Disease

PubMed Central

Furmanik, Malgorzata; Shanahan, Catherine M.

2017-01-01

Cardiovascular disease continues to be the leading cause of death in industrialised societies. The idea that the arterial smooth muscle cell (ASMC) plays a key role in regulating many vascular pathologies has been gaining importance, as has the realisation that not enough is known about the pathological cellular mechanisms regulating ASMC function in vascular remodelling. In the past decade endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) have been recognised as a stress response underlying many physiological and pathological processes in various vascular cell types. Here we summarise what is known about how ER stress signalling regulates phenotypic switching, trans/dedifferentiation and apoptosis of ASMCs and contributes to atherosclerosis, hypertension, aneurysms and vascular calcification.

Successful Use of Dose Dense Neoadjuvant Chemotherapy and Sodium Valproate with Minimal Toxicity in an Infant with Medulloblastoma in Extremely Poor General Condition.

PubMed

Gupta, Ajay; Kumar, Amit; Abrari, Andaleeb; Patir, Rana; Vaishya, Sandeep

2016-09-01

Medulloblastoma is the most common malignant brain tumor in children. Infants are in the high-risk category. Complete surgical resection is the single most important determinant of prognosis and survival in nonmetastatic disease. Infants with large primaries after incomplete resection/biopsy and poor general condition have bad prognosis. They are considered poor candidates for intensive chemotherapy involving high dose methotrexate/autologous stem cell transplantation as they are often unable to tolerate these aggressive regimens. The patient, withinfantile medulloblastoma, was supposed to have complete resection but only a biopsy could be attempted because of increased tumor vascularity. He was in very poor general condition after surgery and his parents declined aggressive chemotherapy and shunt surgery. He was given dose dense neo-adjuvant chemotherapy along with the histone deactylase inhibitor valproate for 5 cycles, with minimal toxicity, after which the tumor was resected. The examination of the resected specimen revealed a complete pathologic response. He then received a total of 18 cycles of chemotherapy and valproate to complete 1 year of systemic treatment. The child is now 6.5 years of age, disease-free, without evidence of any neurocognitive or developmental abnormalities. We suggest that the role of neoadjuvant chemotherapy should be explored in patients with infantile medulloblastoma in whom upfront complete resection is not possible, considering the gratifying results obtained in our case. Copyright © 2016 Elsevier Inc. All rights reserved.

Pathology economic model tool: a novel approach to workflow and budget cost analysis in an anatomic pathology laboratory.

PubMed

Muirhead, David; Aoun, Patricia; Powell, Michael; Juncker, Flemming; Mollerup, Jens

2010-08-01

The need for higher efficiency, maximum quality, and faster turnaround time is a continuous focus for anatomic pathology laboratories and drives changes in work scheduling, instrumentation, and management control systems. To determine the costs of generating routine, special, and immunohistochemical microscopic slides in a large, academic anatomic pathology laboratory using a top-down approach. The Pathology Economic Model Tool was used to analyze workflow processes at The Nebraska Medical Center's anatomic pathology laboratory. Data from the analysis were used to generate complete cost estimates, which included not only materials, consumables, and instrumentation but also specific labor and overhead components for each of the laboratory's subareas. The cost data generated by the Pathology Economic Model Tool were compared with the cost estimates generated using relative value units. Despite the use of automated systems for different processes, the workflow in the laboratory was found to be relatively labor intensive. The effect of labor and overhead on per-slide costs was significantly underestimated by traditional relative-value unit calculations when compared with the Pathology Economic Model Tool. Specific workflow defects with significant contributions to the cost per slide were identified. The cost of providing routine, special, and immunohistochemical slides may be significantly underestimated by traditional methods that rely on relative value units. Furthermore, a comprehensive analysis may identify specific workflow processes requiring improvement.

The Incremental Value of Subjective and Quantitative Assessment of 18F-FDG PET for the Prediction of Pathologic Complete Response to Preoperative Chemoradiotherapy in Esophageal Cancer.

PubMed

van Rossum, Peter S N; Fried, David V; Zhang, Lifei; Hofstetter, Wayne L; van Vulpen, Marco; Meijer, Gert J; Court, Laurence E; Lin, Steven H

2016-05-01

A reliable prediction of a pathologic complete response (pathCR) to chemoradiotherapy before surgery for esophageal cancer would enable investigators to study the feasibility and outcome of an organ-preserving strategy after chemoradiotherapy. So far no clinical parameters or diagnostic studies are able to accurately predict which patients will achieve a pathCR. The aim of this study was to determine whether subjective and quantitative assessment of baseline and postchemoradiation (18)F-FDG PET can improve the accuracy of predicting pathCR to preoperative chemoradiotherapy in esophageal cancer beyond clinical predictors. This retrospective study was approved by the institutional review board, and the need for written informed consent was waived. Clinical parameters along with subjective and quantitative parameters from baseline and postchemoradiation (18)F-FDG PET were derived from 217 esophageal adenocarcinoma patients who underwent chemoradiotherapy followed by surgery. The associations between these parameters and pathCR were studied in univariable and multivariable logistic regression analysis. Four prediction models were constructed and internally validated using bootstrapping to study the incremental predictive values of subjective assessment of (18)F-FDG PET, conventional quantitative metabolic features, and comprehensive (18)F-FDG PET texture/geometry features, respectively. The clinical benefit of (18)F-FDG PET was determined using decision-curve analysis. A pathCR was found in 59 (27%) patients. A clinical prediction model (corrected c-index, 0.67) was improved by adding (18)F-FDG PET-based subjective assessment of response (corrected c-index, 0.72). This latter model was slightly improved by the addition of 1 conventional quantitative metabolic feature only (i.e., postchemoradiation total lesion glycolysis; corrected c-index, 0.73), and even more by subsequently adding 4 comprehensive (18)F-FDG PET texture/geometry features (corrected c-index, 0.77). However, at a decision threshold of 0.9 or higher, representing a clinically relevant predictive value for pathCR at which one may be willing to omit surgery, there was no clear incremental value. Subjective and quantitative assessment of (18)F-FDG PET provides statistical incremental value for predicting pathCR after preoperative chemoradiotherapy in esophageal cancer. However, the discriminatory improvement beyond clinical predictors does not translate into a clinically relevant benefit that could change decision making. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Interoception in pathological health anxiety.

PubMed

Krautwurst, Susann; Gerlach, Alexander L; Witthöft, Michael

2016-11-01

According to cognitive-behavioral models, pathological health anxiety is triggered and maintained by the perception of mostly mild and benign bodily sensations that are misinterpreted as signs of illness. Arguably, abnormalities in interoception may account for this misguided preoccupation with somatic sensations. Using a multimethod approach, the current study investigated possible abnormalities in interoception in patients with pathological health anxiety (PHA; n = 51) and healthy participants (n = 56). Different types of interoception were assessed with a heartbeat-tracking task and a signal-detection task for nonspecific skin conductance fluctuations (NSCFs task). Patients compared with healthy participants showed a more liberal interoceptive response bias for NSCFs, t(79) = 2.32, p = .02, d = 0.53, 95% confidence interval (CI) (0.30, 0.68). Specifically, patients with a comorbid anxiety disorder compared with healthy participants exhibited a significantly higher interoceptive sensitivity for NSCFs, t(57) = 3.12, p < .01, d = 0.89, 95% CI (0.54, 1.12). No evidence for higher interoceptive sensitivity in PHA (neither in the heartbeat mental tracking task nor in the NSCF task) was observed after accounting for comorbid anxiety disorders. The findings suggest that higher interoceptive sensitivity might not be specific to health anxiety, but rather associated with factors shared with the anxiety disorders. Biased (i.e., more liberal) interoceptive processing appears more specific to health anxiety, but further studies using larger sample sizes and a multimethod approach for the assessment of interoception are needed to more completely unravel the role of interoception in health anxiety. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Chocolate craving and disordered eating. Beyond the gender divide?

PubMed

Hormes, Julia M; Orloff, Natalia C; Timko, C Alix

2014-12-01

Chocolate craving in women has previously been linked to disordered eating behaviors. A relatively higher prevalence of eating disorder pathology may account for the fact that chocolate craving is significantly more common in women in North America, compared to many other countries. While support for a causal role of disordered eating in the etiology of craving in women is growing, little is known about the extent to which food cravings are associated with disordered eating behaviors in men. This study was designed to systematically assess the impact of gender and chocolate craving on measures of attitudes to chocolate, responsiveness to food cues in the environment, body shape dissatisfaction, dietary restraint, and eating disorder and general pathology. Undergraduate men and women (n = 645, 37.2% male) were invited to complete self-report questionnaires assessing demographics, height and weight, food cravings, dietary attitudes and behaviors, along with eating disorder and general pathology. Data suggest that the relationship between chocolate craving and disordered eating behaviors in men is the opposite of what has previously been observed in women: compared to non-cravers, male chocolate cravers reported significantly more guilt related to craving, but were significantly less likely to diet and reported lower levels of dietary restraint, less frequent weight fluctuations, and fewer symptoms of eating disorders. Findings indicate that a positive relationship between disordered eating behaviors and chocolate craving may be unique to women (and potentially women in North America). Findings have important implications for our understanding of cultural and psychosocial factors involved in the etiology of food cravings. Copyright © 2014 Elsevier Ltd. All rights reserved.

Efficient and Reproducible Myogenic Differentiation from Human iPS Cells: Prospects for Modeling Miyoshi Myopathy In Vitro

PubMed Central

Tanaka, Akihito; Woltjen, Knut; Miyake, Katsuya; Hotta, Akitsu; Ikeya, Makoto; Yamamoto, Takuya; Nishino, Tokiko; Shoji, Emi; Sehara-Fujisawa, Atsuko; Manabe, Yasuko; Fujii, Nobuharu; Hanaoka, Kazunori; Era, Takumi; Yamashita, Satoshi; Isobe, Ken-ichi; Kimura, En; Sakurai, Hidetoshi

2013-01-01

The establishment of human induced pluripotent stem cells (hiPSCs) has enabled the production of in vitro, patient-specific cell models of human disease. In vitro recreation of disease pathology from patient-derived hiPSCs depends on efficient differentiation protocols producing relevant adult cell types. However, myogenic differentiation of hiPSCs has faced obstacles, namely, low efficiency and/or poor reproducibility. Here, we report the rapid, efficient, and reproducible differentiation of hiPSCs into mature myocytes. We demonstrated that inducible expression of myogenic differentiation1 (MYOD1) in immature hiPSCs for at least 5 days drives cells along the myogenic lineage, with efficiencies reaching 70–90%. Myogenic differentiation driven by MYOD1 occurred even in immature, almost completely undifferentiated hiPSCs, without mesodermal transition. Myocytes induced in this manner reach maturity within 2 weeks of differentiation as assessed by marker gene expression and functional properties, including in vitro and in vivo cell fusion and twitching in response to electrical stimulation. Miyoshi Myopathy (MM) is a congenital distal myopathy caused by defective muscle membrane repair due to mutations in DYSFERLIN. Using our induced differentiation technique, we successfully recreated the pathological condition of MM in vitro, demonstrating defective membrane repair in hiPSC-derived myotubes from an MM patient and phenotypic rescue by expression of full-length DYSFERLIN (DYSF). These findings not only facilitate the pathological investigation of MM, but could potentially be applied in modeling of other human muscular diseases by using patient-derived hiPSCs. PMID:23626698

Major histocompatibility complex class II molecule expression on muscle cells is regulated by differentiation: implications for the immunopathogenesis of muscle autoimmune diseases.

PubMed

Mantegazza, R; Gebbia, M; Mora, M; Barresi, R; Bernasconi, P; Baggi, F; Cornelio, F

1996-08-01

Major histocompatibility complex (MHC) class II molecules are expressed on myoblasts after interferon-gamma (IFN-gamma) treatment, suggesting a muscle cell involvement in antigen presentation in inflammatory myopathies. However, they were not observed on normal or pathological myofibers. This discrepancy might be related to different responsiveness of developmentally differentiated muscle cells to IFN-gamma. Myoblasts expressed class II transcripts and proteins after IFN-gamma, while myotubes and innervated contracting muscle cells did not show staining for class II molecules. At all cell stages no loss of IFN-gamma receptor was detected indicating that myofiber maturation blocks their capacity to express MHC class II molecules. This suggests that completely differentiated myofibers cannot participate in class II restricted immunological reactions.

Distinct chronology of neuronal cell cycle re-entry and tau pathology in the 3xTg-AD mouse model and Alzheimer's disease patients.

PubMed

Hradek, Alex C; Lee, Hyun-Pil; Siedlak, Sandra L; Torres, Sandy L; Jung, Wooyoung; Han, Ashley H; Lee, Hyoung-gon

2015-01-01

Cell cycle re-entry in Alzheimer's disease (AD) has emerged as an important pathological mechanism in the progression of the disease. This appearance of cell cycle related proteins has been linked to tau pathology in AD, but the causal and temporal relationship between the two is not completely clear. In this study, we found that hyperphosphorylated retinoblastoma protein (ppRb), a key regulator for G1/S transition, is correlated with a late marker for hyperphosphorylation of tau but not with other early markers for tau alteration in the 3xTg-AD mouse model. However, in AD brains, ppRb can colocalize with both early and later markers for tau alterations, and can often be found singly in many degenerating neurons, indicating the distinct development of pathology between the 3xTg-AD mouse model and human AD patients. The conclusions of this study are two-fold. First, our findings clearly demonstrate the pathological link between the aberrant cell cycle re-entry and tau pathology. Second, the chronological pattern of cell cycle re-entry with tau pathology in the 3xTg-AD mouse is different compared to AD patients suggesting the distinct pathogenic mechanism between the animal AD model and human AD patients.

Design and Implementation of the Retinoblastoma Collaborative Laboratory.

PubMed

Qaiser, Seemi; Limo, Alice; Gichana, Josiah; Kimani, Kahaki; Githanga, Jessie; Waweru, Wairimu; Dimba, Elizabeth A O; Dimaras, Helen

2017-01-01

The purpose of this work was to describe the design and implementation of a digital pathology laboratory, the Retinoblastoma Collaborative Laboratory (RbCoLab) in Kenya. The RbCoLab is a central lab in Nairobi that receives retinoblastoma specimens from all over Kenya. Specimens were processed using evidence-based standard operating procedures. Images were produced by a digital scanner, and pathology reports were disseminated online. The lab implemented standard operating procedures aimed at improving the accuracy, completeness, and timeliness of pathology reports, enhancing the care of Kenyan retinoblastoma patients. Integration of digital technology to support pathology services supported knowledge transfer and skills transfer. A bidirectional educational network of local pathologists and other clinicians in the circle of care of the patients emerged and served to emphasize the clinical importance of cancer pathology at multiple levels of care. A 'Robin Hood' business model of health care service delivery was developed to support sustainability and scale-up of cancer pathology services. The application of evidence-based protocols, comprehensive training, and collaboration were essential to bring improvements to the care of retinoblastoma patients in Kenya. When embraced as an integrated component of retinoblastoma care, digital pathology offers the opportunity for frequent connection and consultation for development of expertise over time.

Design and Implementation of the Retinoblastoma Collaborative Laboratory

PubMed Central

Qaiser, Seemi; Limo, Alice; Gichana, Josiah; Kimani, Kahaki; Githanga, Jessie; Waweru, Wairimu; Dimba, Elizabeth A.O.; Dimaras, Helen

2017-01-01

Purpose The purpose of this work was to describe the design and implementation of a digital pathology laboratory, the Retinoblastoma Collaborative Laboratory (RbCoLab) in Kenya. Method The RbCoLab is a central lab in Nairobi that receives retinoblastoma specimens from all over Kenya. Specimens were processed using evidence-based standard operating procedures. Images were produced by a digital scanner, and pathology reports were disseminated online. Results The lab implemented standard operating procedures aimed at improving the accuracy, completeness, and timeliness of pathology reports, enhancing the care of Kenyan retinoblastoma patients. Integration of digital technology to support pathology services supported knowledge transfer and skills transfer. A bidirectional educational network of local pathologists and other clinicians in the circle of care of the patients emerged and served to emphasize the clinical importance of cancer pathology at multiple levels of care. A ‘Robin Hood’ business model of health care service delivery was developed to support sustainability and scale-up of cancer pathology services. Discussion The application of evidence-based protocols, comprehensive training, and collaboration were essential to bring improvements to the care of retinoblastoma patients in Kenya. When embraced as an integrated component of retinoblastoma care, digital pathology offers the opportunity for frequent connection and consultation for development of expertise over time. PMID:28275608

Sustainable Development of Pathology in Sub-Saharan Africa: An Example From Ghana.

PubMed

Stalsberg, Helge; Adjei, Ernest Kwasi; Owusu-Afriyie, Osei; Isaksen, Vidar

2017-11-01

- Pathology services are poorly developed in Sub-Saharan Africa. Komfo Anokye Teaching Hospital in Kumasi, Ghana, asked for help from the pathology department of the University Hospital of North Norway, Tromsø. - To reestablish surgical pathology and cytology in an African pathology department in which these functions had ceased completely, and to develop the department into a self-supporting unit of good international standard and with the capacity to train new pathologists. - Medical technologists from Kumasi were trained in histotechnology in Norway, they were returned to Kumasi, and they produced histologic slides that were temporarily sent to Norway for diagnosis. Two Ghanaian doctors received pathology training for 4 years in Norway. Mutual visits by pathologists and technologists from the 2 hospitals were arranged for the introduction of immunohistochemistry and cytology. Pathologists from Norway visited Kumasi for 1 month each year during 2007-2010. Microscopes and immunohistochemistry equipment were provided from Norway. Other laboratory equipment and a new building were provided by the Ghanaian hospital. - The Ghanaian hospital had a surgical pathology service from the first project year. At 11 years after the start of the project, the services included autopsy, surgical pathology, cytopathology, frozen sections, and limited use of immunohistochemistry, and the department had 10 residents at different levels of training. - A Ghanaian pathology department that performed autopsies only was developed into a self-supported department with surgical pathology, cytology, immunohistochemistry, and frozen section service, with an active residency program and the capacity for further development that is independent from assistance abroad.

Correlation between expressions of ERCC1/TS mRNA and effects of gastric cancer to chemotherapy in the short term.

PubMed

Chen, Liqi; Li, Guoli; Li, Jieshou; Fan, Chaogang; Xu, Jian; Wu, Bo; Liu, Kun; Zhang, Caihua

2013-04-01

To study the correlation between expression levels of ERCC1/TS mRNA and the susceptibility of preoperative chemotherapy for patients with gastric cancer. A total of forty cases with advanced gastric cancer of T3-4N1-2M0 were treated with preoperative chemotherapy according to FLEEOX regimen based on endarterial-intravenous coadministration. Sufficient, fresh gastric tissue specimens were obtained with the help of gastroscope, and the expression levels of ERCC1/TS mRNA were detected by qRT-PCR before chemotherapy. The chemotherapeutic response was evaluated with Choi Criteria after chemotherapy, and pathologic remission extent was observed after surgery. The correlation between the expression levels of ERCC1/TS mRNA before chemotherapy and the chemotherapeutic effect based on imageology and pathology was analyzed. The response rate of Chemotherapy in this cohort was 80.0 % based on imageology and 51.43 % based on pathology. The expression levels of ERCC1/TS mRNA were significantly associated with imageology remission extent (P = 0.033, P = 0.025) and pathologic remission extent (P = 0.044, P = 0.016), respectively. The chemotherapeutic effect on patients with low-expression levels of ERCC1/TS mRNA was better. From the perspective of pathology and imageology evaluating the preoperative chemotherapeutic response for patients with gastric cancer, ERCC1 and TS were used as the molecular predictors and provided prognostic information in this study.

Underlying chronic inflammation alters the profile and mechanisms of acute neutrophil recruitment.

PubMed

Ma, Bin; Whiteford, James R; Nourshargh, Sussan; Woodfin, Abigail

2016-11-01

Chronically inflamed tissues show altered characteristics that include persistent populations of inflammatory leukocytes and remodelling of the vascular network. As the majority of studies on leukocyte recruitment have been carried out in normal healthy tissues, the impact of underlying chronic inflammation on ongoing leukocyte recruitment is largely unknown. Here, we investigate the profile and mechanisms of acute inflammatory responses in chronically inflamed and angiogenic tissues, and consider the implications for chronic inflammatory disorders. We have developed a novel model of chronic ischaemia of the mouse cremaster muscle that is characterized by a persistent population of monocyte-derived cells (MDCs), and capillary angiogenesis. These tissues also show elevated acute neutrophil recruitment in response to locally administered inflammatory stimuli. We determined that Gr1 low MDCs, which are widely considered to have anti-inflammatory and reparative functions, amplified acute inflammatory reactions via the generation of additional proinflammatory signals, changing both the profile and magnitude of the tissue response. Similar vascular and inflammatory responses, including activation of MDCs by transient ischaemia-reperfusion, were observed in mouse hindlimbs subjected to chronic ischaemia. This response demonstrates the relevance of the findings to peripheral arterial disease, in which patients experience transient exercise-induced ischaemia known as claudication.These findings demonstrate that chronically inflamed tissues show an altered profile and altered mechanisms of acute inflammatory responses, and identify tissue-resident MDCs as potential therapeutic targets. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Intraoperative optical assessment of photodynamic therapy response of superficial oral squamous cell carcinoma

NASA Astrophysics Data System (ADS)

Rohrbach, Daniel J.; Rigual, Nestor; Arshad, Hassan; Tracy, Erin C.; Cooper, Michelle T.; Shafirstein, Gal; Wilding, Gregory; Merzianu, Mihai; Baumann, Heinz; Henderson, Barbara W.; Sunar, Ulas

2016-01-01

This study investigated whether diffuse optical spectroscopy (DOS) measurements could assess clinical response to photodynamic therapy (PDT) in patients with head and neck squamous cell carcinoma (HNSCC). In addition, the correlation between parameters measured with DOS and the crosslinking of signal transducer and activator of transcription 3 (STAT3), a molecular marker for PDT-induced photoreaction, was investigated. Thirteen patients with early stage HNSCC received the photosensitizer 2-[1-hexyloxyethyl]-2-devinylpyropheophorbide-a (HPPH) and DOS measurements were performed before and after PDT in the operating room (OR). In addition, biopsies were acquired after PDT to assess the STAT3 crosslinking. Parameters measured with DOS, including blood volume fraction, blood oxygen saturation (StO2), HPPH concentration (cHPPH), HPPH fluorescence, and blood flow index (BFI), were compared to the pathologic response and the STAT3 crosslinking. The best individual predictor of pathological response was a change in cHPPH (sensitivity=60%, specificity=100%), while discrimination analysis using a two-parameter classifier (change in cHPPH and change in StO2) classified pathological response with 100% sensitivity and 100% specificity. BFI showed the best correlation with the crosslinking of STAT3. These results indicate that DOS-derived parameters can assess the clinical response in the OR, allowing for earlier reintervention if needed.

Entheseal changes and pathological lesions in draught reindeer skeletons - Four case studies from present-day Siberia.

PubMed

Salmi, Anna-Kaisa; Niinimäki, Sirpa

2016-09-01

Draught use and being ridden often result in typical pathological patterns in animal skeletons. Moreover, physical activity patterns may be reflected in bone biomechanical properties and entheseal changes at muscle attachment sites. This paper presents the pathologies and entheseal changes observed in four draught and/or racing reindeer skeletons against information on their life histories and discusses the probability of linking the observed changes to their use. The results of this study are a useful point of comparison to researchers working on reindeer and other species of draught animals. However, our results also emphasize that entheseal changes and many pathologies have multifactorial etiologies and that interpretation of skeletal change patterns is not straightforward, even when there is information on the life history of the animal and its complete skeleton can be examined. Copyright © 2016 Elsevier Inc. All rights reserved.

Eating Pathology, Emotion Regulation, and Emotional Overeating in Obese Adults with Binge Eating Disorder

PubMed Central

Gianini, Loren M.; White, Marney A.; Masheb, Robin M.

2013-01-01

Objective The purpose of the current study was to examine the relationship among emotional regulation, emotional overeating, and general eating pathology in a treatment seeking sample of adults with Binge Eating Disorder (BED). Method The sample was composed of 326 adults (248 women, 78 men) who were obese and met DSM-IV-TR criteria for BED. Prior to treatment, participants completed the Difficulties in Emotion Regulation Scale (DERS), Emotional Overeating Questionnaire (EOQ), Beck Depression Inventory (BDI), and Eating Disorder Examination-Questionnaire (EDE-Q) as part of a larger assessment battery. Results A series of hierarchical regression analyses indicated that difficulties with emotion regulation accounted for unique variance in both emotional overeating and general eating pathology above and beyond sex and negative affect. Discussion Emotion regulation may play a significant role in the maintenance of emotional overeating and eating pathology in obese adults with BED. PMID:23910772

Eating pathology, emotion regulation, and emotional overeating in obese adults with Binge Eating Disorder.

PubMed

Gianini, Loren M; White, Marney A; Masheb, Robin M

2013-08-01

The purpose of the current study was to examine the relationship among emotional regulation, emotional overeating, and general eating pathology in a treatment seeking sample of adults with Binge Eating Disorder (BED). The sample was composed of 326 adults (248 women, 78 men) who were obese and met DSM-IV-TR criteria for BED. Prior to treatment, participants completed the Difficulties in Emotion Regulation Scale (DERS), Emotional Overeating Questionnaire (EOQ), Beck Depression Inventory (BDI), and Eating Disorder Examination-Questionnaire (EDE-Q) as part of a larger assessment battery. A series of hierarchical regression analyses indicated that difficulties with emotion regulation accounted for unique variance in both emotional overeating and general eating pathology above and beyond sex and negative affect. Emotion regulation may play a significant role in the maintenance of emotional overeating and eating pathology in obese adults with BED. Copyright © 2013 Elsevier Ltd. All rights reserved.

Ventromedial prefrontal cortex activity and pathological worry in generalised anxiety disorder.

PubMed

Via, E; Fullana, M A; Goldberg, X; Tinoco-González, D; Martínez-Zalacaín, I; Soriano-Mas, C; Davey, C G; Menchón, J M; Straube, B; Kircher, T; Pujol, J; Cardoner, N; Harrison, B J

2018-05-09

Pathological worry is a hallmark feature of generalised anxiety disorder (GAD), associated with dysfunctional emotional processing. The ventromedial prefrontal cortex (vmPFC) is involved in the regulation of such processes, but the link between vmPFC emotional responses and pathological v. adaptive worry has not yet been examined.AimsTo study the association between worry and vmPFC activity evoked by the processing of learned safety and threat signals. In total, 27 unmedicated patients with GAD and 56 healthy controls (HC) underwent a differential fear conditioning paradigm during functional magnetic resonance imaging. Compared to HC, the GAD group demonstrated reduced vmPFC activation to safety signals and no safety-threat processing differentiation. This response was positively correlated with worry severity in GAD, whereas the same variables showed a negative and weak correlation in HC. Poor vmPFC safety-threat differentiation might characterise GAD, and its distinctive association with GAD worries suggests a neural-based qualitative difference between healthy and pathological worries.Declaration of interestNone.

RandomizEd controlled trial for pre-operAtive dose-escaLation BOOST in locally advanced rectal cancer (RECTAL BOOST study): study protocol for a randomized controlled trial.

PubMed

Burbach, J P Maarten; Verkooijen, Helena M; Intven, Martijn; Kleijnen, Jean-Paul J E; Bosman, Mirjam E; Raaymakers, Bas W; van Grevenstein, Wilhelmina M U; Koopman, Miriam; Seravalli, Enrica; van Asselen, Bram; Reerink, Onne

2015-02-22

Treatment for locally advanced rectal cancer (LARC) consists of chemoradiation therapy (CRT) and surgery. Approximately 15% of patients show a pathological complete response (pCR). Increased pCR-rates can be achieved through dose escalation, thereby increasing the number patients eligible for organ-preservation to improve quality of life (QoL). A randomized comparison of 65 versus 50Gy with external-beam radiation alone has not yet been performed. This trial investigates pCR rate, clinical response, toxicity, QoL and (disease-free) survival in LARC patients treated with 65Gy (boost + chemoradiation) compared with 50Gy standard chemoradiation (sCRT). This study follows the 'cohort multiple randomized controlled trial' (cmRCT) design: rectal cancer patients are included in a prospective cohort that registers clinical baseline, follow-up, survival and QoL data. At enrollment, patients are asked consent to offer them experimental interventions in the future. Eligible patients-histologically confirmed LARC (T3NxM0 <1 mm from mesorectal fascia, T4NxM0 or TxN2M0) located ≤10 cm from the anorectal transition who provided consent for experimental intervention offers-form a subcohort (n = 120). From this subcohort, a random sample is offered the boost prior to sCRT (n = 60), which they may accept or refuse. Informed consent is signed only after acceptance of the boost. Non-selected patients in the subcohort (n = 60) undergo sCRT alone and are not notified that they participate in the control arm until the trial is completed. sCRT consists of 50Gy (25 × 2Gy) with concomitant capecitabine. The boost (without chemotherapy) is given prior to sCRT and consists of 15 Gy (5 × 3Gy) delivered to the gross tumor volume (GTV). The primary endpoint is pCR (TRG 1). Secondary endpoints include acute grade 3-4 toxicity, good pathologic response (TRG 1-2), clinical response, surgical complications, QoL and (disease-free) survival. Data is analyzed by intention to treat. The boost is delivered prior to sCRT so that GTV adjustment for tumor shrinkage during sCRT is not necessary. Small margins also aim to limit irradiation of healthy tissue. The cmRCT design provides opportunity to overcome common shortcomings of classic RCTs, such as slow recruitment, disappointment-bias in control arm patients and poor generalizability. The Netherlands Trials Register NL46051.041.13. Registered 22 August 2013. ClinicalTrials.gov NCT01951521 . Registered 18 September 2013.

High wall shear stress and spatial gradients in vascular pathology: a review.

PubMed

Dolan, Jennifer M; Kolega, John; Meng, Hui

2013-07-01

Cardiovascular pathologies such as intracranial aneurysms (IAs) and atherosclerosis preferentially localize to bifurcations and curvatures where hemodynamics are complex. While extensive knowledge about low wall shear stress (WSS) has been generated in the past, due to its strong relevance to atherogenesis, high WSS (typically >3 Pa) has emerged as a key regulator of vascular biology and pathology as well, receiving renewed interests. As reviewed here, chronic high WSS not only stimulates adaptive outward remodeling, but also contributes to saccular IA formation (at bifurcation apices or outer curves) and atherosclerotic plaque destabilization (in stenosed vessels). Recent advances in understanding IA pathogenesis have shed new light on the role of high WSS in pathological vascular remodeling. In complex geometries, high WSS can couple with significant spatial WSS gradient (WSSG). A combination of high WSS and positive WSSG has been shown to trigger aneurysm initiation. Since endothelial cells (ECs) are sensors of WSS, we have begun to elucidate EC responses to high WSS alone and in combination with WSSG. Understanding such responses will provide insight into not only aneurysm formation, but also plaque destabilization and other vascular pathologies and potentially lead to improved strategies for disease management and novel targets for pharmacological intervention.

Cue-induced brain activity in pathological gamblers.

PubMed

Crockford, David N; Goodyear, Bradley; Edwards, Jodi; Quickfall, Jeremy; el-Guebaly, Nady

2005-11-15

Previous studies using functional magnetic resonance imaging (fMRI) have identified differential brain activity in healthy subjects performing gambling tasks and in pathological gambling (PG) subjects when exposed to motivational and emotional predecessors for gambling as well as during gambling or response inhibition tasks. The goal of the present study was to determine if PG subjects exhibit differential brain activity when exposed to visual gambling cues. Ten male DSM-IV-TR PG subjects and 10 matched healthy control subjects underwent fMRI during visual presentations of gambling-related video alternating with video of nature scenes. Pathological gambling subjects and control subjects exhibited overlap in areas of brain activity in response to the visual gambling cues; however, compared with control subjects, PG subjects exhibited significantly greater activity in the right dorsolateral prefrontal cortex (DLPFC), including the inferior and medial frontal gyri, the right parahippocampal gyrus, and left occipital cortex, including the fusiform gyrus. Pathological gambling subjects also reported a significant increase in mean craving for gambling after the study. Post hoc analyses revealed a dissociation in visual processing stream (dorsal vs. ventral) activation by subject group and cue type. These findings may represent a component of cue-induced craving for gambling or conditioned behavior that could underlie pathological gambling.