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Talhouk A.,University of British Columbia | Kommoss S.,University Hospital of Tuebingen | Mackenzie R.,University of British Columbia | Cheung M.,British Columbia Center for Disease Control | And 14 more authors.
PLoS ONE | Year: 2016

A major weakness in many high-throughput genomic studies is the lack of consideration of a clinical environment where one patient at a time must be evaluated. We examined generalizable and platform-specific sources of variation from NanoString gene expression data on both ovarian cancer and Hodgkin lymphoma patients. A reference-based strategy, applicable to single-patient molecular testing is proposed for batch effect correction. The proposed protocol improved performance in an established Hodgkin lymphoma classifier, reducing batch-to-batch misclassification while retaining accuracy and precision. We suggest this strategy may facilitate development of NanoString and similar molecular assays by accelerating prospective validation and clinical uptake of relevant diagnostics. © 2016 Talhouk et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Objective: To identify clinical factors associated with prostate cancer (PCA) upgrading to higher patterns of the surgical specimen in low-risk PCA. Materials and Methods: We evaluated the records of 438 patients. The multinomial logistic regression model was used. Results: Low-risk PCA included 170 cases (38.8%) and tumor upgrading was detected in 111 patients (65.3%) of whom 72 (42.4%) had pathological Gleason patterns (pGP) = 3 + 4 and 39 (22.9%) pGP >3 + 4. Prostate-specific antigen (PSA) and proportion of positive cores (P+) were independent predictors of tumor upgrading to higher patterns. The main difference between upgraded cancers related to PSA and to P+ >0.20. The population was stratified into risk classes by PSA ≤5 μg/l and P+ ≤0.20 (class A), PSA >5 μg/l and P+ ≤0.20 (class B), PSA ≤5 μg/l and P+ >0.20 (class C) and PSA >5 μg/l and P+ 0.20 (class D). Upgrading rates to pGP >3 + 4 were extremely low in class A (5.1%), extremely high in D (53.8%). Conclusions: Low-risk PCA is a heterogeneous population with significant rates of undetected high-grade disease. Significant clinical predictors of upgrading to higher patterns include PSA and P+, which identify a very high-risk class that needs repeat biopsies in order to reclassify tumor grade. © 2016 S. Karger AG, Basel. Copyright: All rights reserved.

Johung K.,Yale University | Saif M.W.,Columbia University | Saif M.W.,Pancreas Center | Chang B.W.,Yale University
International Journal of Radiation Oncology Biology Physics | Year: 2012

Pancreatic cancer remains associated with an extremely poor prognosis. Surgical resection can be curative, but the majority of patients present with locally advanced or metastatic disease. Treatment for patients with locally advanced disease is controversial. Therapeutic options include systemic therapy alone, concurrent chemoradiation, or induction chemotherapy followed by chemoradiation. We review the evidence to date regarding the treatment of locally advanced pancreatic cancer (LAPC), as well as evolving strategies including the emerging role of targeted therapies. We propose that if radiation is used for patients with LAPC, it should be delivered with concurrent chemotherapy and following a period of induction chemotherapy. © 2012 Elsevier Inc.

Hyun O J.,Johns Hopkins University | Lodge M.A.,Johns Hopkins University | Jagannath S.,Pancreas Center | Olagbemiro Y.,Johns Hopkins University | Wahl R.L.,Johns Hopkins University
Journal of Nuclear Medicine | Year: 2014

The purpose of this study was to develop a noninvasive imaging test of pancreatic exocrine function. Methods: In this pilot study, 5 healthy volunteers underwent two 60-min dynamic 11C-acetate PET studies, one before and one after intravenous secretin administration. Kinetic analysis of the pancreas was performed using a 1-compartment model and an image-derived input function. From summed images, standardized uptake values were measured from the pancreas and the liver, and the pancreas-to-liver ratio was computed. Results: The baseline k1 and k2 data for all 5 volunteers were consistent. After secretin stimulation, the k1 and k2 significantly increased (paired t test P = 0.046 and P = 0.023, respectively). In the summed PET images, the pancreas-to-liver ratio decreased (P = 0.037). Increased 11C-acetate activity was observed in the duodenum after secretin stimulation consistent with secretin-induced secretion. Conclusion: 11C-acetate PET studies with secretin stimulation show potential as a noninvasive method for assessing pancreatic exocrine function. Copyright © 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

O'Connor K.,Vancouver General Hospital | O'Connor K.,University of British Columbia | Li-Chang H.H.,Vancouver General Hospital | Li-Chang H.H.,University of British Columbia | And 21 more authors.
American Journal of Surgical Pathology | Year: 2015

Tumor budding is a well-established adverse prognostic factor in colorectal cancer. However, the significance and diagnostic reproducibility of budding in pancreatic carcinoma requires further study. We aimed to assess the prognostic significance of tumor budding in pancreatic ductal adenocarcinoma, determine its relationship with other clinicopathologic features, and assess interobserver variability in its diagnosis. Tumor budding was assessed in 192 archival cases of pancreatic ductal adenocarcinoma using hematoxylin and eosin (H&E) sections; tumor buds were defined as single cells or nonglandular clusters composed of <5 cells. The presence of budding was determined through assessment of all tumor-containing slides, and associations with clinicopathologic features and outcomes were analyzed. Six gastrointestinal pathologists participated in an interobserver variability study of 120 images of consecutive tumor slides stained with H&E and cytokeratin. Budding was present in 168 of 192 cases and was associated with decreased overall survival (P=0.001). On multivariable analysis, tumor budding was prognostically significantly independent of stage, grade, tumor size, nodal status, lymphovascular invasion, and perineural invasion. There was substantial agreement among pathologists in assessing the presence of tumor budding using both H&E (K=0.63) and cytokeratin (K=0.63) stains. The presence of tumor budding is an independent adverse prognostic factor in pancreatic ductal carcinoma. The assessment of budding with H&E is reliable and could be used to better risk stratify patients with pancreatic ductal adenocarcinoma. © 2015 Wolters Kluwer Health, Inc.

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