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Pancreatic Neoplasms: HELP
Articles by Steven E. Kalloger
Based on 6 articles published since 2009
(Why 6 articles?)
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Between 2009 and 2019, Steve E. Kalloger wrote the following 6 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Article Molecular characterization of metastatic pancreatic neuroendocrine tumors (PNETs) using whole-genome and transcriptome sequencing. 2018

Wong, Hui-Li / Yang, Kevin C / Shen, Yaoqing / Zhao, Eric Y / Loree, Jonathan M / Kennecke, Hagen F / Kalloger, Steve E / Karasinska, Joanna M / Lim, Howard J / Mungall, Andrew J / Feng, Xiaolan / Davies, Janine M / Schrader, Kasmintan / Zhou, Chen / Karsan, Aly / Jones, Steven J M / Laskin, Janessa / Marra, Marco A / Schaeffer, David F / Gorski, Sharon M / Renouf, Daniel J. ·Division of Medical Oncology, BC Cancer Agency, Vancouver, British Columbia V5Z 4E6, Canada. · Pancreas Centre BC, Vancouver, British Columbia V5Z 4E6, Canada. · Department of Molecular Biology and Biochemistry, Simon Fraser University, Vancouver, British Columbia V5A 1S6, Canada. · Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, British Columbia V5Z 4S6, Canada. · Division of Anatomical Pathology, Vancouver General Hospital, Vancouver, British Columbia V5Z 1M9, Canada. · Vancouver Island Centre, British Columbia Cancer Agency, Vancouver, British Columbia V8R 6V5, Canada. · Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada. ·Cold Spring Harb Mol Case Stud · Pubmed #29092957.

ABSTRACT: Pancreatic neuroendocrine tumors (PNETs) are a genomically and clinically heterogeneous group of pancreatic neoplasms often diagnosed with distant metastases. Recurrent somatic mutations, chromosomal aberrations, and gene expression signatures in PNETs have been described, but the clinical significance of these molecular changes is still poorly understood, and the clinical outcomes of PNET patients remain highly variable. To help identify the molecular factors that contribute to PNET progression and metastasis, and as part of an ongoing clinical trial at the BC Cancer Agency (clinicaltrials.gov ID: NCT02155621), the genomic and transcriptomic profiles of liver metastases from five patients (four PNETs and one neuroendocrine carcinoma) were analyzed. In four of the five cases, we identified biallelic loss of

2 Article Programmed cell death ligand 1 cut-point is associated with reduced disease specific survival in resected pancreatic ductal adenocarcinoma. 2017

Tessier-Cloutier, Basile / Kalloger, Steve E / Al-Kandari, Mohammad / Milne, Katy / Gao, Dongxia / Nelson, Brad H / Renouf, Daniel J / Sheffield, Brandon S / Schaeffer, David F. ·Division of Anatomical Pathology, Vancouver General Hospital, Vancouver, British Columbia, Canada. · Department of Pathology & Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada. · Department of Pathology & Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada. skalloger@mac.com. · Pancreas Centre BC, Vancouver, British Columbia, Canada. skalloger@mac.com. · Division of Medical Oncology, British Columbia Cancer Agency, Vancouver, British Columbia, Canada. skalloger@mac.com. · Department of Anatomical Pathology, Abbotosford Regional Hospital and Cancer Centre, Abbotsford, British Columbia, Canada. skalloger@mac.com. · Deeley Research Centre, British Columbia Cancer Agency, Victoria, British Columbia, Canada. · Division of Medical Oncology, University of British Columbia , Vancouver, British Columbia, Canada. · Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada. · Pancreas Centre BC, Vancouver, British Columbia, Canada. · Division of Medical Oncology, British Columbia Cancer Agency, Vancouver, British Columbia, Canada. · Department of Anatomical Pathology, Abbotosford Regional Hospital and Cancer Centre, Abbotsford, British Columbia, Canada. · Genetic Pathology Evaluation Centre, University of British Columbia, Vancouver, British Columbia, Canada. ·BMC Cancer · Pubmed #28870260.

ABSTRACT: BACKGROUND: Programmed cell death 1 (PD1) inhibitors have recently shown promising anti-cancer effects in a number of solid tumor types. A predictive biomarker to this class of drugs has not been clearly identified; however, overexpression of the PD1 ligand (PD-L1) has shown particular promise in lung adenocarcinoma. In this study, we explore the staining characteristics, prevalence, and clinico-molecular correlates of PD-L1 overexpression in pancreatic ductal adenocarcinoma (PDAC). METHODS: A tissue microarray (TMA) was constructed from cases of resected PDAC. PD-L1 immunohistochemistry (IHC) was performed using the SP142 primary antibody. Immunohistochemical assessment for deficient mismatch repair status (MMRd), CD3 and CD8 were performed. All biomarkers were assessed independently by two anatomical pathologists and consensus achieved on all cases. Survival analysis was performed using three thresholds (> = 1%, >5% and >10%) for tumor cell membrane staining. RESULTS: Two-hundred fifty-two cases were included in the TMA and evaluable by IHC. Thirty-one (12%), 17 (7%), 12(5%) cases were positive at percentage cut offs of >0, >5, and >10% respectively. Increased PD-L1 expression was associated with inferior prognosis (p = 0.0367). No statistically significant association was identified between PD-L1 status and MMR status or tumor infiltrating lymphocytes. CONCLUSIONS: This data suggests that there is an inverse relationship between PD-L1 expression and disease specific survival times in resected PDAC. Consequently, this association may represent a phenotype where increased PD-L1 expression has an effect on tumor biology and could therefore identify a subgroup where PD1 blockade could have enhanced effectiveness.

3 Article Immunophenotyping of ampullary carcinomata allows for stratification of treatment specific subgroups. 2016

Leo, Joyce M / Kalloger, Steve E / Peixoto, Renata D / Gale, Nadia S / Webber, Douglas L / Owen, David A / Renouf, Daniel / Schaeffer, David F. ·Division of Anatomic Pathology, Vancouver General Hospital, Vancouver, British Columbia, Canada The University of British Columbia, Vancouver, British Columbia, Canada. · The University of British Columbia, Vancouver, British Columbia, Canada Pancreas Centre BC, Vancouver, British Columbia, Canada. · Division of Medical Oncology, BC Cancer Agency, Vancouver, British Columbia, Canada. · Anatomical Pathology, BC Cancer Agency, Vancouver, British Columbia, Canada. · Division of Anatomic Pathology, Vancouver General Hospital, Vancouver, British Columbia, Canada The University of British Columbia, Vancouver, British Columbia, Canada Pancreas Centre BC, Vancouver, British Columbia, Canada. · The University of British Columbia, Vancouver, British Columbia, Canada Pancreas Centre BC, Vancouver, British Columbia, Canada Division of Medical Oncology, BC Cancer Agency, Vancouver, British Columbia, Canada. ·J Clin Pathol · Pubmed #26500334.

ABSTRACT: BACKGROUND: Ampullary carcinomata (AC) can be separated into intestinal (IT) or pancreatobiliary (PB) subtypes. Although morphological, immunohistochemical and molecular differentiation of IT and PB have been well documented; the prognostic significance of histological subtype and whether patients with either subtype benefit from differential chemotherapeutic regimens remains unclear. METHODS: As part of a larger cohort study, patients who underwent resection for AC or pancreatic ductal adenocarcinoma (PDAC) were retrospectively identified. Clinicopathological covariates and outcome were obtained and MUC1, MUC2, CDX2 and CK20 were assessed with immunohistochemistry. RESULTS: Of 99 ACs, the resultant immunophenotypes indicated 48% and 22% were IT and PB, respectively. Thirty (30%) cases were quadruple negative (QN). Within the PDAC cohort (N = 257), the most prevalent immunophenotype was QN (53%). Subsequently, all QN ACs were classified as PB immunohistochemically yielding 47.5% and 52.5% classified as IT and PB, respectively. Involved regional lymph nodes and elevated T-stage were significantly associated with PB compared with IT AC (p = 0.0032 and 0.0396, respectively). Progression-free survival revealed inferior survival for PB versus IT AC (p = 0.0156). CONCLUSIONS: AC can be classified into prognostic groups with unique clinicopathological characteristics using immunohistochemistry. Immunophenotypical similarity of PB and PDAC suggests that treatment regimens similar to those used in PDAC should be explored.

4 Article Ductal pancreatic cancer modeling and drug screening using human pluripotent stem cell- and patient-derived tumor organoids. 2015

Huang, Ling / Holtzinger, Audrey / Jagan, Ishaan / BeGora, Michael / Lohse, Ines / Ngai, Nicholas / Nostro, Cristina / Wang, Rennian / Muthuswamy, Lakshmi B / Crawford, Howard C / Arrowsmith, Cheryl / Kalloger, Steve E / Renouf, Daniel J / Connor, Ashton A / Cleary, Sean / Schaeffer, David F / Roehrl, Michael / Tsao, Ming-Sound / Gallinger, Steven / Keller, Gordon / Muthuswamy, Senthil K. ·Princess Margaret Cancer Center, University Health Network (UHN), University of Toronto, Toronto, Ontario, Canada. · McEwen Center for Regenerative Medicine, University Health Network, Toronto, Ontario, Canada. · Department of Physiology, Western University, London, Ontario, Canada. · Department of Pharmacology, Western University, London, Ontario, Canada. · Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan. · Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan. · Structural Genomics Consortium, Toronto, Ontario, Canada. · Division of Anatomic Pathology, Vancouver General Hospital, Vancouver, British Columbia, Canada. · Department of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada. · Pancreas Centre British Columbia, Vancouver, British Columbia, Canada. · Division of Medical Oncology, British Columbia Cancer Agency, Vancouver, British Columbia, Canada. · Division of General Surgery, University of Toronto, Toronto, Ontario, Canada. · Department of Pathology, University Health Network, Toronto, Ontario, Canada. ·Nat Med · Pubmed #26501191.

ABSTRACT: There are few in vitro models of exocrine pancreas development and primary human pancreatic adenocarcinoma (PDAC). We establish three-dimensional culture conditions to induce the differentiation of human pluripotent stem cells into exocrine progenitor organoids that form ductal and acinar structures in culture and in vivo. Expression of mutant KRAS or TP53 in progenitor organoids induces mutation-specific phenotypes in culture and in vivo. Expression of TP53(R175H) induces cytosolic SOX9 localization. In patient tumors bearing TP53 mutations, SOX9 was cytoplasmic and associated with mortality. We also define culture conditions for clonal generation of tumor organoids from freshly resected PDAC. Tumor organoids maintain the differentiation status, histoarchitecture and phenotypic heterogeneity of the primary tumor and retain patient-specific physiological changes, including hypoxia, oxygen consumption, epigenetic marks and differences in sensitivity to inhibition of the histone methyltransferase EZH2. Thus, pancreatic progenitor organoids and tumor organoids can be used to model PDAC and for drug screening to identify precision therapy strategies.

5 Article Mismatch repair status may predict response to adjuvant chemotherapy in resectable pancreatic ductal adenocarcinoma. 2015

Riazy, Maziar / Kalloger, Steve E / Sheffield, Brandon S / Peixoto, Renata D / Li-Chang, Hector H / Scudamore, Charles H / Renouf, Daniel J / Schaeffer, David F. ·Division of Anatomic Pathology, Vancouver General Hospital, Vancouver, British Columbia, Canada. · Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada. · Pancreas Centre BC, Vancouver, British Columbia, Canada. · Division of Medical Oncology, BC Cancer Agency, Vancouver, British Columbia, Canada. · Division of General Surgery, Vancouver General Hospital, Vancouver, British Columbia, Canada. ·Mod Pathol · Pubmed #26226846.

ABSTRACT: 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.

6 Article Tumor budding is an independent adverse prognostic factor in pancreatic ductal adenocarcinoma. 2015

O'Connor, Kate / Li-Chang, Hector H / Kalloger, Steven E / Peixoto, Renata D / Webber, Douglas L / Owen, David A / Driman, David K / Kirsch, Richard / Serra, Stefano / Scudamore, Charles H / Renouf, Daniel J / Schaeffer, David F. ·Divisions of *Anatomic Pathology #General Surgery, Vancouver General Hospital †The University of British Columbia ‡Pancreas Centre BC §Division of Medical Oncology, BC Cancer Agency, Vancouver, BC ∥Department of Pathology, Western University, London ¶Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada. ·Am J Surg Pathol · Pubmed #25634751.

ABSTRACT: 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.