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Pancreatic Neoplasms: HELP
Articles by Sangeetha N. Kalimuthu
Based on 4 articles published since 2009
(Why 4 articles?)
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Between 2009 and 2019, Sangeetha Kalimuthu wrote the following 4 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Review Intraductal tubular neoplasms of the pancreas: an overview. 2016

Chelliah, Adeline / Kalimuthu, Sangeetha / Chetty, Runjan. ·Department of Pathology, Laboratory Medicine Program, University Health Network and University of Toronto, Toronto, Canada. · Department of Pathology, Laboratory Medicine Program, University Health Network and University of Toronto, Toronto, Canada. Electronic address: runjan.chetty@gmail.com. ·Ann Diagn Pathol · Pubmed #27185640.

ABSTRACT: Intraductal lesions of the pancreas are an uncommon but increasingly recognized group of entities mainly because of advances in imaging technology. In the past, precise categorization and understanding of true pancreatic intraduct neoplasms were hampered not only by their relative rarity but also because of the plethora of terminology and criteria used in nomenclature and diagnosis. Although significant progress has been made in the characterization of some of these lesions, as exemplified by intraductal papillary mucinous neoplasms, understanding of the rare intraductal tubular adenoma (ITA) and intraduct tubular carcinoma (ITC) continues to evolve. By definition, these are a group of intraductal, radiologically detectable neoplasms that can progress to or be associated with invasive adenocarcinoma and, as such, are precursor lesions to pancreatic ductal adenocarcinoma. Their often shared clinical and radiological features make precise histological diagnosis essential for appropriate management and optimal outcome. We provide an overview of these neoplasms and highlight recent developments in the understanding of ITA and ITC which have led to ITA being considered a variant of gastric-type intraductal papillary mucinous neoplasms and ITC being encompassed within the intraductal tubulopapillary neoplasm category. We also emphasize the distinguishing histological features to aid diagnosis of these rare lesions.

2 Review The spectrum of histopathological changes encountered in pancreatectomy specimens after neoadjuvant chemoradiation, including subtle and less-well-recognised changes. 2016

Kalimuthu, Sangeetha N / Serra, Stefano / Dhani, Neesha / Chetty, Runjan. ·Departments of Pathology, Laboratory Medicine Program and *Medical Oncology, University Health Network and University of Toronto, Toronto, Canada. ·J Clin Pathol · Pubmed #26915370.

ABSTRACT: Preoperative (neoadjuvant) chemoradiation therapy/treatment (NCRT) is emerging as an important treatment modality in borderline resectable pancreatic ductal adenocarcinoma (PDAC). The constellation of histopathological changes secondary to chemoradiation is diverse and has been well documented, particularly in other gastrointestinal organs such as the oesophagus and colorectum. However, the histological changes specific to the pancreas have not been fully characterised and described. This review aims to provide a detailed catalogue of histological features associated with NCRT-treated PDAC and highlight any subtle, less-recognised changes.

3 Article Primary inferior vena cava smooth muscle tumor with diffuse bizarre giant nuclei and low mitotic rate: a nomenclatural conundrum. 2017

Chetty, Runjan / Kalimuthu, Sangeetha N / Heinonen, Hanna-Riikka. ·Department of Pathology, Laboratory Medicine Program, University Health Network and University of Toronto, Toronto M5G 2C4, Canada. Electronic address: runjan.chetty@gmail.com. · Department of Pathology, Laboratory Medicine Program, University Health Network and University of Toronto, Toronto M5G 2C4, Canada. · Department of Medical and Clinical Genetics and Genome-Scale Biology Research Program, P.O. Box 63, FIN-00014, University of Helsinki, Helsinki, Finland. ·Cardiovasc Pathol · Pubmed #28623706.

ABSTRACT: A male patient with obstructive jaundice was found to have an incidental nodule within the inferior vena cava (IVC), below the level of the renal vein, on abdominal imaging. At the time of the Whipple's procedure for pancreatic adenocarcinoma, the IVC mass measuring 3.4×2.7×2.2 cm was also removed. Histologically, the lesion was well circumscribed, composed focally of spindle-shaped cells with cigar-shaped nuclei reminiscent of smooth muscle and a dominant pervasive, pleomorphic, bizarre giant cell component. Two mitoses per 10 high-power fields were identified in the most mitotically active area of the entire tumor, with the vast majority of the tumor being mitotically inert. Additionally, no evidence of coagulative necrosis was noted. The bizarre giant cells had multi- and polylobated configurations, and several were replete with nuclear pseudoinclusions. Both the spindle cell and pleomorphic components displayed strong immunoreactivity for all smooth muscle markers. This lesion conformed morphologically to a smooth muscle tumor with bizarre nuclei or so-called symplastic/bizarre leiomyoma, as encountered in the uterus. However, current thinking based on location in the IVC and the presence of any mitotic activity with cellular atypia makes this lesion a leiomyosarcoma. Perhaps more pragmatic terminology would be smooth muscle tumor with bizarre nuclei and low malignant potential since the limited number of cases described thus far appear to have a more indolent course.

4 Article Association of Distinct Mutational Signatures With Correlates of Increased Immune Activity in Pancreatic Ductal Adenocarcinoma. 2017

Connor, Ashton A / Denroche, Robert E / Jang, Gun Ho / Timms, Lee / Kalimuthu, Sangeetha N / Selander, Iris / McPherson, Treasa / Wilson, Gavin W / Chan-Seng-Yue, Michelle A / Borozan, Ivan / Ferretti, Vincent / Grant, Robert C / Lungu, Ilinca M / Costello, Eithne / Greenhalf, William / Palmer, Daniel / Ghaneh, Paula / Neoptolemos, John P / Buchler, Markus / Petersen, Gloria / Thayer, Sarah / Hollingsworth, Michael A / Sherker, Alana / Durocher, Daniel / Dhani, Neesha / Hedley, David / Serra, Stefano / Pollett, Aaron / Roehrl, Michael H A / Bavi, Prashant / Bartlett, John M S / Cleary, Sean / Wilson, Julie M / Alexandrov, Ludmil B / Moore, Malcolm / Wouters, Bradly G / McPherson, John D / Notta, Faiyaz / Stein, Lincoln D / Gallinger, Steven. ·PanCuRx Translational Research Initiative, Ontario Institute for Cancer Research, Toronto, Ontario, Canada2Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada3Hepatobiliary/Pancreatic Surgical Oncology Program, University Health Network, Toronto, Ontario, Canada. · PanCuRx Translational Research Initiative, Ontario Institute for Cancer Research, Toronto, Ontario, Canada4Informatics and Bio-computing Program, Ontario Institute for Cancer Research, Toronto, Ontario, Canada. · PanCuRx Translational Research Initiative, Ontario Institute for Cancer Research, Toronto, Ontario, Canada4Informatics and Bio-computing Program, Ontario Institute for Cancer Research, Toronto, Ontario, Canada5Department of Statistical Science, University of Toronto, Toronto, Ontario, Canada. · PanCuRx Translational Research Initiative, Ontario Institute for Cancer Research, Toronto, Ontario, Canada6Genome Technologies Program, Ontario Institute for Cancer Research, Toronto, Ontario, Canada. · PanCuRx Translational Research Initiative, Ontario Institute for Cancer Research, Toronto, Ontario, Canada. · Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada. · Informatics and Bio-computing Program, Ontario Institute for Cancer Research, Toronto, Ontario, Canada. · PanCuRx Translational Research Initiative, Ontario Institute for Cancer Research, Toronto, Ontario, Canada2Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada. · Transformative Pathology, Ontario Institute for Cancer Research, Toronto, Ontario, Canada. · University of Liverpool, Liverpool, England. · Heidelberg University Hospital, Heidelberg, Germany. · Mayo Clinic, Rochester, Minnesota. · Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts. · University of Nebraska Medical Centre, Omaha, Nebraska. · Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada13Molecular Genetics Department, University of Toronto, Toronto, Ontario, Canada. · Division of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada. · Hepatobiliary/Pancreatic Surgical Oncology Program, University Health Network, Toronto, Ontario, Canada. · Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada15Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada. · PanCuRx Translational Research Initiative, Ontario Institute for Cancer Research, Toronto, Ontario, Canada15Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada16Department of Pathology, University Health Network, Toronto, Ontario, Canada17Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada18BioSpecimen Sciences Program, University Health Network, Toronto, Ontario, Canada. · PanCuRx Translational Research Initiative, Ontario Institute for Cancer Research, Toronto, Ontario, Canada3Hepatobiliary/Pancreatic Surgical Oncology Program, University Health Network, Toronto, Ontario, Canada. · Theoretical Biology and Biophysics (T-6), Los Alamos National Laboratory, Los Alamos, New Mexico20Center for Nonlinear Studies, Los Alamos National Laboratory, Los Alamos, New Mexico. · Department of Pathology, University Health Network, Toronto, Ontario, Canada. · Genome Technologies Program, Ontario Institute for Cancer Research, Toronto, Ontario, Canada17Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada. · Informatics and Bio-computing Program, Ontario Institute for Cancer Research, Toronto, Ontario, Canada13Molecular Genetics Department, University of Toronto, Toronto, Ontario, Canada. ·JAMA Oncol · Pubmed #27768182.

ABSTRACT: Importance: Outcomes for patients with pancreatic ductal adenocarcinoma (PDAC) remain poor. Advances in next-generation sequencing provide a route to therapeutic approaches, and integrating DNA and RNA analysis with clinicopathologic data may be a crucial step toward personalized treatment strategies for this disease. Objective: To classify PDAC according to distinct mutational processes, and explore their clinical significance. Design, Setting, and Participants: We performed a retrospective cohort study of resected PDAC, using cases collected between 2008 and 2015 as part of the International Cancer Genome Consortium. The discovery cohort comprised 160 PDAC cases from 154 patients (148 primary; 12 metastases) that underwent tumor enrichment prior to whole-genome and RNA sequencing. The replication cohort comprised 95 primary PDAC cases that underwent whole-genome sequencing and expression microarray on bulk biospecimens. Main Outcomes and Measures: Somatic mutations accumulate from sequence-specific processes creating signatures detectable by DNA sequencing. Using nonnegative matrix factorization, we measured the contribution of each signature to carcinogenesis, and used hierarchical clustering to subtype each cohort. We examined expression of antitumor immunity genes across subtypes to uncover biomarkers predictive of response to systemic therapies. Results: The discovery cohort was 53% male (n = 79) and had a median age of 67 (interquartile range, 58-74) years. The replication cohort was 50% male (n = 48) and had a median age of 68 (interquartile range, 60-75) years. Five predominant mutational subtypes were identified that clustered PDAC into 4 major subtypes: age related, double-strand break repair, mismatch repair, and 1 with unknown etiology (signature 8). These were replicated and validated. Signatures were faithfully propagated from primaries to matched metastases, implying their stability during carcinogenesis. Twelve of 27 (45%) double-strand break repair cases lacked germline or somatic events in canonical homologous recombination genes-BRCA1, BRCA2, or PALB2. Double-strand break repair and mismatch repair subtypes were associated with increased expression of antitumor immunity, including activation of CD8-positive T lymphocytes (GZMA and PRF1) and overexpression of regulatory molecules (cytotoxic T-lymphocyte antigen 4, programmed cell death 1, and indolamine 2,3-dioxygenase 1), corresponding to higher frequency of somatic mutations and tumor-specific neoantigens. Conclusions and Relevance: Signature-based subtyping may guide personalized therapy of PDAC in the context of biomarker-driven prospective trials.