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.
Sankpal U.T.,Cancer Research Institute |
Maliakal P.,Cancer Research Institute |
Bose D.,Cancer Research Institute |
Bose D.,Pancreas Center |
And 7 more authors.
Current Medicinal Chemistry | Year: 2012
Pancreatic cancer is an aggressive malignancy with poor prognosis. Pancreatic adenocarcinoma is one of the leading causes of cancer-related deaths in the United States. Due to the aggressive nature of this malignancy, there is a serious concern for identifying effective targets, and adopting novel strategies for therapy. Members of the Specificity Protein (Sp) family of transcription factors, Sp1, Sp3, and Sp4 regulate the expression of a number of genes associated with cancer cell proliferation, differentiation, and metastasis. Sp1 levels are upregulated in pancreatic cancer cell lines, and surgically resected human pancreatic adenocarcinoma. Sp1 overexpression in tumor tissues is associated with aggressive disease, poor prognosis and inversely correlated with survival. Sp1 is also known to affect angiogenesis by regulating the expression of vascular endothelial growth factor and its receptors. Results from clinical studies suggest Sp1 as new biomarker to identify aggressive pancreatic ductal adenocarcinoma. The pharmacological inhibition of Sp1 using agents such as celecoxib, mithramycin, curcumin, and tolfenamic acid has showed promising results in pre-clinical studies and demonstrated Sp transcription factors as potential targets for pancreatic cancer therapy. This review summarizes studies showing the association of Sp proteins with this malignancy, with a special emphasis on pre-clinical studies that tested strategies to target Sp transcription factors for inhibiting human pancreatic cancer cell proliferation and tumor growth in laboratory animals. The results showed remarkable efficacy and suggest that such approaches have the potential for high success in developing clinically relevant strategies for treating pancreatic cancer. © 2012 Bentham Science Publishers.
Low-Risk Prostate Cancer and Tumor Upgrading to Higher Patterns in the Surgical Specimen. Analysis of Clinical Factors Predicting Tumor Upgrading to Higher Gleason Patterns in a Contemporary Series of Patients Who Have Been Evaluated According to the Modified Gleason Score Grading System
Porcaro A.B.,Urologic |
Porcaro A.B.,Pancreas Center |
Siracusano S.,Urologic |
De Luyk N.,Urologic |
And 10 more authors.
Urologia Internationalis | Year: 2016
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.
Robotic-assisted radical prostatectomy is less stressful than the open approach: results of a contemporary prospective study evaluating pathophysiology of cortisol stress-related kinetics in prostate cancer surgery
Porcaro A.B.,Urologic |
Porcaro A.B.,Pancreas Center |
Molinari A.,Urologic |
Terrin A.,Urologic |
And 9 more authors.
Journal of Robotic Surgery | Year: 2015
The objective of this study was to investigate the effects of prostate cancer (PCA) surgery on the stress system and to identify potential independent factors associating with stress recovery. The design of the study was prospective and PCA surgery included robot-assisted radical prostatectomy (RARP) or retro pubic radical prostatectomy. Between February and December 2013, 151 consecutive patients were evaluated. The effects of PCA surgery on the stress system were measured by cortisol serum levels before and after surgery on post-operative day (POD) 0, 1, 3, 5 and 45. Statistical methods were applied. RARP was performed in 71 % of cases. PCA surgery triggered the stress system which immediately (POD 0) responded by cortisol overproduction which induced the negative feedback mechanism that started on POD 1, continued on POD. © 2015, Springer-Verlag London.
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.
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.
Riazy M.,Vancouver General Hospital |
Riazy M.,University of British Columbia |
Kalloger S.E.,University of British Columbia |
Kalloger S.E.,Pancreas Center |
And 14 more authors.
Modern Pathology | Year: 2015
Deficiencies in DNA mismatch repair have been associated with inferior response to 5-FU in colorectal cancer. Pancreatic ductal adenocarcinoma is similarly treated with pyrimidine analogs, yet the predictive value of mismatch repair status for response to these agents has not been examined in this malignancy. A tissue microarray with associated clinical outcome, comprising 254 resected pancreatic ductal adenocarcinoma patients was stained for four mismatch repair proteins (MLH1, MSH2, MSH6 and PMS2). Mismatch repair deficiency and proficiency was determined by the absence or presence of uniform nuclear staining in tumor cells, respectively. Cases identified as mismatch repair deficient on the tissue microarray were confirmed by immunohistochemistry on whole slide sections. Of the 265 cases, 78 (29%) received adjuvant treatment with a pyrimidine analog and 41 (15%) showed a mismatch repair-deficient immunoprofile. Multivariable disease-specific survival in the mismatch repair-proficient cohort demonstrated that adjuvant chemotherapy, regional lymph-node status, gender, and the presence of tumor budding were significant independent prognostic variables (P≤0.04); however, none of the eight clinico-pathologic covariates examined in the mismatch repair-deficient cohort were of independent prognostic significance. Univariable assessment of disease-specific survival revealed an almost identical survival profile for both treated and untreated patients with a mismatch repair-deficient profile, while treatment in the mismatch repair-proficient cohort conferred a greater than 10-month median disease-specific survival advantage over their untreated counterparts (P=0.0018). In this cohort, adjuvant chemotherapy with a pyrimidine analog conferred no survival advantage to mismatch repair-deficient pancreatic ductal adenocarcinoma patients. Mismatch repair immunoprofiling is a feasible predictive marker in pancreatic ductal adenocarcinoma patients, and further prospective evaluation of this finding is warranted. © 2015 USCAP, Inc All rights reserved.
O'connor K.,Vancouver General Hospital |
O'connor K.,University of British Columbia |
Cheriyan D.G.,Vancouver General Hospital |
Cheriyan D.G.,University of British Columbia |
And 19 more authors.
Acta Cytologica | Year: 2015
Background: Endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA) is the preferred method for biopsying the gastrointestinal tract, and rapid on-site cytological evaluation is considered standard practice. Our institution does not perform on-site evaluation; this study analyzes our overall diagnostic yield, accuracy, and incidence of nondiagnostic cases to determine the validity of this strategy. Design: Data encompassing clinical information, procedural records, and cytological assessment were analyzed for gastrointestinal EUS-FNA procedures (n = 85) performed at Vancouver General Hospital from January 2012 to January 2013. We compared our results with those of studies that had on-site evaluation and studies that did not have on-site evaluation. Results: Eighty-five biopsies were performed in 78 patients, from sites that included the pancreas, the stomach, the duodenum, lymph nodes, and retroperitoneal masses. Malignancies were diagnosed in 45 (53%) biopsies, while 24 (29%) encompassed benign entities. Suspicious and atypical results were recorded in 8 (9%) and 6 (7%) cases, respectively. Only 2 (2%) cases received a cytological diagnosis of 'nondiagnostic'. Our overall accuracy was 72%, our diagnostic yield was 98%, and our nondiagnostic rate was 2%. Our results did not significantly differ from those of studies that did have on-site evaluation. Conclusion: Our study highlights that adequate diagnostic accuracy can be achieved without on-site evaluation. © 2015 S. Karger AG, Basel.
Gawlas I.,Columbia University Medical Center |
Sethi M.,Columbia University Medical Center |
Winner M.,Columbia University Medical Center |
Epelboym I.,Columbia University Medical Center |
And 8 more authors.
Annals of Surgical Oncology | Year: 2013
Background: Hospital readmission has been proposed as a metric for quality of medical and surgical care. We examined our institutional experience with readmission after pancreatic resection, and assessed factors predictive of readmission. Methods: We reviewed 787 pancreatic resections performed at a single institution between 2006 and 2010. Univariate and multivariate logistic regression models were used to assess the relationships between preoperative and postoperative characteristics and readmission. Reasons for hospital readmission were examined in detail. Results: We found the 30-day readmission rate after pancreatic resection to be 11.6 %. In univariate analysis, young age, pancreaticoduodenectomy versus other operations, open versus laparoscopic technique, fistula formation, the need for reoperation, and any complication during the index hospitalization were predictive of readmission. In multivariate analysis, only young age and postoperative complication were predictive of readmission. Vascular resection, postoperative ICU care, length of stay, and discharge disposition were not associated with readmission. The most common reasons for readmission were leaks, fistulas, abscesses, and wound infections (45.1 %), delayed gastric emptying (12.1 %), venous thrombosis (7.7 %), and GI bleeding (7.7 %). Conclusions: We found the vast majority of readmissions after pancreatic resection were to manage complications related to the operation and were not due to poor coordination of care or poor discharge planning. Because evidence-based measures to prevent these surgical complications do not exist, we cannot support the use of readmission rates themselves as a quality indicator after pancreatic surgery. © 2012 Society of Surgical Oncology.
PubMed | University of British Columbia, Pancreas Center and British Columbia Cancer Agency
Type: Journal Article | Journal: Cancer medicine | Year: 2015
Due to differences in natural history and therapy, clinical trials of patients with advanced pancreatic cancer have recently been subdivided into unresectable locally advanced pancreatic cancer (LAPC) and metastatic disease. We aimed to evaluate prognostic factors in LAPC patients who were treated with first-line chemotherapy and describe patterns of disease progression. Patients with LAPC who initiated first-line palliative chemotherapy, 2001-2011 at the BC Cancer Agency were included. A retrospective chart review was conducted to identify clinicopathologic variables, treatment, and subsequent sites of metastasis. Kaplan-Meier and Cox-regression survival analyses were performed. A total of 244 patients were included in this study. For the majority of patients (94.3%), first-line therapy was single-agent gemcitabine. About 144 (59%) patients developed distant metastatic disease and the most frequent metastatic sites included peritoneum/omentum (42.3%), liver (41%), lungs (13.9%), and distant lymph nodes (9%). Median overall survival (OS) for the entire cohort was 11.7 months (95% CI, 10.6-12.8). Development of distant metastases was associated with significantly inferior survival (HR 3.56, 95% CI 2.57-4.93), as was ECOG 2/3 versus 0/1 (HR 1.69, 95% CI 1.28-2.23), CA 19.9 > 1000 versus 1000 (HR 1.59, 95% CI 1.19-2.14) and female gender, (HR 1.57, 95% CI 1.19-2.08). In this population-based study, 41% of LAPC patients treated with first-line chemotherapy died without evidence of distant metastases. Prognostic factors for LAPC were baseline performance status, elevated CA 19.9, gender, and development of distant metastasis. Results highlight the heterogeneity of LAPC and the importance of locoregional tumor control.