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Pancreatic Neoplasms: HELP
Articles by David S. Klimstra
Based on 104 articles published since 2008
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Between 2008 and 2019, D. Klimstra wrote the following 104 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5
1 Guideline Pathologic Evaluation and Reporting of Intraductal Papillary Mucinous Neoplasms of the Pancreas and Other Tumoral Intraepithelial Neoplasms of Pancreatobiliary Tract: Recommendations of Verona Consensus Meeting. 2016

Adsay, Volkan / Mino-Kenudson, Mari / Furukawa, Toru / Basturk, Olca / Zamboni, Giuseppe / Marchegiani, Giovanni / Bassi, Claudio / Salvia, Roberto / Malleo, Giuseppe / Paiella, Salvatore / Wolfgang, Christopher L / Matthaei, Hanno / Offerhaus, G Johan / Adham, Mustapha / Bruno, Marco J / Reid, Michelle D / Krasinskas, Alyssa / Klöppel, Günter / Ohike, Nobuyuki / Tajiri, Takuma / Jang, Kee-Taek / Roa, Juan Carlos / Allen, Peter / Fernández-del Castillo, Carlos / Jang, Jin-Young / Klimstra, David S / Hruban, Ralph H / Anonymous6200823. ·*Department of Pathology, Emory University School of Medicine and Winship Cancer Institute, Atlanta, GA †Department of Pathology, Massachusetts General Hospital, Boston, MA ‡Department of Pathology, Tokyo Women's Medical University, Tokyo, Japan §Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY ¶Department of Pathology, University of Verona, Verona, Italy ||Department of Surgery, Massachusetts General Hospital, Boston, MA **Department of Surgery, University of Verona, Verona, Italy ††Department of Surgery, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD ‡‡Departments of Surgery, University of Bonn, Bonn, Germany §§Departments of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands ¶¶Department of Surgery, Edouard Herriot Hospital, HCL, Lyon, France ||||Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands ***Departments of Pathology, Technical University, Munich, Germany †††Department of Pathology, Showa University Fujigaoka Hospital, Yokohama, Japan ‡‡‡Department of Pathology, Tokai University Hachioji Hospital, Tokyo, Japan §§§Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea ¶¶¶Department of Pathology, Pontificia Universidad Católica de Chile, Santiago, Chile ||||||Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY ****Department of Surgery, Massachusetts General Hospital, Boston, MA ††††Department of Surgery, Seoul National University Hospital, Seoul, Korea ‡‡‡‡Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD. ·Ann Surg · Pubmed #25775066.

ABSTRACT: BACKGROUND: There are no established guidelines for pathologic diagnosis/reporting of intraductal papillary mucinous neoplasms (IPMNs). DESIGN: An international multidisciplinary group, brought together by the Verona Pancreas Group in Italy-2013, was tasked to devise recommendations. RESULTS: (1) Crucial to rule out invasive carcinoma with extensive (if not complete) sampling. (2) Invasive component is to be documented in a full synoptic report including its size, type, grade, and stage. (3) The term "minimally invasive" should be avoided; instead, invasion size with stage and substaging of T1 (1a, b, c; ≤ 0.5, > 0.5-≤ 1, > 1 cm) is to be documented. (4) Largest diameter of the invasion, not the distance from the nearest duct, is to be used. (5) A category of "indeterminate/(suspicious) for invasion" is acceptable for rare cases. (6) The term "malignant" IPMN should be avoided. (7) The highest grade of dysplasia in the non-invasive component is to be documented separately. (8) Lesion size is to be correlated with imaging findings in cysts with rupture. (9) The main duct diameter and, if possible, its involvement are to be documented; however, it is not required to provide main versus branch duct classification in the resected tumor. (10) Subtyping as gastric/intestinal/pancreatobiliary/oncocytic/mixed is of value. (11) Frozen section is to be performed highly selectively, with appreciation of its shortcomings. (12) These principles also apply to other similar tumoral intraepithelial neoplasms (mucinous cystic neoplasms, intra-ampullary, and intra-biliary/cholecystic). CONCLUSIONS: These recommendations will ensure proper communication of salient tumor characteristics to the management teams, accurate comparison of data between analyses, and development of more effective management algorithms.

2 Guideline NANETS treatment guidelines: well-differentiated neuroendocrine tumors of the stomach and pancreas. 2010

Kulke, Matthew H / Anthony, Lowell B / Bushnell, David L / de Herder, Wouter W / Goldsmith, Stanley J / Klimstra, David S / Marx, Stephen J / Pasieka, Janice L / Pommier, Rodney F / Yao, James C / Jensen, Robert T / Anonymous4950666. ·Department of Medical Oncology, Dana-Farber Cancer Institute, Boston MA 02115, USA. Matthew_kulke@dfci.harvard.edu ·Pancreas · Pubmed #20664472.

ABSTRACT: Well-differentiated neuroendocrine tumors (NETs) of the stomach and pancreas represent 2 major subtypes of gastrointestinal NETs. Historically, there has been little consensus on the classification and management of patients with these tumor subtypes. We provide an overview of well-differentiated NETs of the stomach and pancreas and describe consensus guidelines for the treatment of patients with these malignancies.

3 Editorial Reassessing the grade of gastroenteropancreatic neuroendocrine neoplasms. 2016

Klimstra, David S. ·Department of Pathology, James Ewing Alumni Chair in Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, USA. klimstrd@mskcc.org. · Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, NY, 10065, USA. klimstrd@mskcc.org. ·Endocrine · Pubmed #27150611.

ABSTRACT: -- No abstract --

4 Editorial Introduction. 2014

Hruban, Ralph H / Klimstra, David S. · ·Semin Diagn Pathol · Pubmed #25441312.

ABSTRACT: -- No abstract --

5 Editorial The ENETS and AJCC/UICC TNM classifications of the neuroendocrine tumors of the gastrointestinal tract and the pancreas: a statement. 2010

Klöppel, Günter / Rindi, Guido / Perren, Aurel / Komminoth, Paul / Klimstra, David S. · ·Virchows Arch · Pubmed #20422210.

ABSTRACT: -- No abstract --

6 Review Well-differentiated pancreatic neuroendocrine tumours (PanNETs) and poorly differentiated pancreatic neuroendocrine carcinomas (PanNECs): concepts, issues and a practical diagnostic approach to high-grade (G3) cases. 2018

Singhi, Aatur D / Klimstra, David S. ·Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. · Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. ·Histopathology · Pubmed #29239037.

ABSTRACT: With increasing accessibility and advancements in abdominal imaging modalities, the incidence of pancreatic neuroendocrine neoplasms has increased steadily during the past few decades. By definition, neuroendocrine neoplasms of the pancreas show neuroendocrine differentiation, but they represent a broad and heterogeneous group of neoplasms with diverse clinical and pathological characteristics. The majority of pancreatic neuroendocrine neoplasms can be classified as well-differentiated pancreatic neuroendocrine tumours (PanNETs) or poorly differentiated pancreatic neuroendocrine carcinomas (PanNECs). While PanNETs and PanNECs are distinct entities with respect to clinical presentation, outcome and therapeutic approach, they may exhibit overlapping histopathological features. Moreover, the frequent modifications in nomenclature and prognostic grading systems over the years of not only pancreatic neuroendocrine neoplasms, but neuroendocrine neoplasms from other organ sites, has created confusion for both pathologists and clinicians as to the appropriate use of terminology and grading when evaluating these neoplasms. This review examines the current concepts and issues of nomenclature and grading of PanNETs and PanNECs. In addition, considering the morphological overlap between high-grade (G3) PanNETs and PanNECs, we discuss an integrative and practical diagnostic approach to aid in discriminating challenging cases.

7 Review Acinar neoplasms of the pancreas-A summary of 25 years of research. 2016

Klimstra, David S / Adsay, Volkan. ·Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065. Electronic address: klimstrd@mskcc.org. · Department of Anatomic Pathology, Emory University, Atlanta, GA. ·Semin Diagn Pathol · Pubmed #27320062.

ABSTRACT: Our understanding about the family of acinar neoplasms of the pancreas has grown substantially over the past 25 years. The prototype is acinar cell carcinoma, an uncommon variant of pancreatic carcinoma that demonstrates production of pancreatic exocrine enzymes, verifiable using immunohistochemistry, and exhibits characteristic histologic features. Related neoplasms include mixed acinar carcinomas such as mixed acinar neuroendocrine carcinoma and mixed acinar ductal carcinoma. In the pediatric age group, pancreatoblastoma is also closely related. Cystic and extrapancreatic forms have been described. These neoplasms share molecular alterations that are distinct from the more common ductal and neuroendocrine neoplasms of the pancreas. Although there is a broad range of genetic findings, a number of potential therapeutic targets have emerged. This review explores the clinical and pathologic features of pancreatic acinar neoplasms along with their more common molecular phenotypes. The differential diagnosis with other pancreatic neoplasms is explored as well.

8 Review Pathologic Classification of Neuroendocrine Neoplasms. 2016

Klimstra, David S. ·Weill Cornell Medical College, 1305 York Avenue, New York, NY 10021, USA; Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. Electronic address: klimstrd@mskcc.org. ·Hematol Oncol Clin North Am · Pubmed #26614366.

ABSTRACT: The pathologic classification of neuroendocrine neoplasms has evolved over the past decades, as new understanding of the biological behavior, histologic characteristics, and genetic features have emerged. Nonetheless, many aspects of the classification systems remain confusing or controversial. Despite these difficulties, much progress has been made in determining the features predicting behavior. Genetic findings have helped establish relationships among different types of neuroendocrine neoplasms and revealed potential therapeutic targets. This review summarizes the current approach to the diagnosis, classification, grading, and therapeutic stratification of neuroendocrine neoplasms, with a focus on those arising in the lung and thymus, pancreas, and intestines.

9 Review The spectrum of neuroendocrine tumors: histologic classification, unique features and areas of overlap. 2015

Klimstra, David S / Beltran, Himisha / Lilenbaum, Rogerio / Bergsland, Emily. ·From the Memorial Sloan Kettering Cancer Center, New York, NY; Weill Cornell Medical College, New York, NY; Yale Cancer Center, New Haven, CT; UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA. ·Am Soc Clin Oncol Educ Book · Pubmed #25993147.

ABSTRACT: Neuroendocrine neoplasms are diverse in terms of sites of origin, functional status, and degrees of aggressiveness. This review will introduce some of the common features of neuroendocrine neoplasms and will explore the differences in pathology, classification, biology, and clinical management between tumors of different anatomic sites, specifically, the lung, pancreas, and prostate. Despite sharing neuroendocrine differentiation and histologic evidence of the neuroendocrine phenotype in most organs, well-differentiated neuroendocrine tumors (WD-NETs) and poorly differentiated neuroendocrine carcinomas (PD-NECs) are two very different families of neoplasms. WD-NETs (grade 1 and 2) are relatively indolent (with a natural history that can evolve over many years or decades), closely resemble non-neoplastic neuroendocrine cells, and demonstrate production of neurosecretory proteins, such as chromogranin A. They arise in the lungs and throughout the gastrointestinal tract and pancreas, but WD-NETs of the prostate gland are uncommon. Surgical resection is the mainstay of therapy, but treatment of unresectable disease depends on the site of origin. In contrast, PD-NECs (grade 3, small cell or large cell) of all sites often demonstrate alterations in P53 and Rb, exhibit an aggressive clinical course, and are treated with platinum-based chemotherapy. Only WD-NETs arise in patients with inherited neuroendocrine neoplasia syndromes (e.g., multiple endocrine neoplasia type 1), and some common genetic alterations are site-specific (e.g., TMPRSS2-ERG gene rearrangement in PD-NECs arising in the prostate gland). Advances in our understanding of the molecular basis of NETs should lead to new diagnostic and therapeutic strategies and is an area of active investigation.

10 Review Early detection of sporadic pancreatic cancer: summative review. 2015

Chari, Suresh T / Kelly, Kimberly / Hollingsworth, Michael A / Thayer, Sarah P / Ahlquist, David A / Andersen, Dana K / Batra, Surinder K / Brentnall, Teresa A / Canto, Marcia / Cleeter, Deborah F / Firpo, Matthew A / Gambhir, Sanjiv Sam / Go, Vay Liang W / Hines, O Joe / Kenner, Barbara J / Klimstra, David S / Lerch, Markus M / Levy, Michael J / Maitra, Anirban / Mulvihill, Sean J / Petersen, Gloria M / Rhim, Andrew D / Simeone, Diane M / Srivastava, Sudhir / Tanaka, Masao / Vinik, Aaron I / Wong, David. ·From the *Department of Medicine, Mayo Clinic, Rochester, MN; †Department of Biomedical Engineering, University of Virginia, Charlottesville, VA; Departments of ‡Biochemistry and Molecular Biology, §Pathology and Microbiology, and ∥Surgery, Fred & Pamela Buffett Cancer Center, University of Nebraska, Omaha, NE; ¶Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, MD; #Division of Gastroenterology, University of Washington, Seattle, WA; **Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, MD; ††Sawgrass Leadership Institute, Ponte Vedra Beach, FL; ‡‡Department of Surgery, University of Utah, Salt Lake City, UT; §§Department of Radiology, Stanford University School of Medicine, Stanford; ∥∥Department of Medicine, David Geffen School of Medicine, and ¶¶General Surgery, University of California Los Angeles, Los Angeles, CA; ##Kenner Family Research Fund; ***Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY; †††Department of Internal Medicine, University of Greifswald, Greifswald, Germany; ‡‡‡Division of Pathology and Laboratory Medicine, University of Texas MD Anderson Cancer Center, Houston, TX; §§§Department of Health Sciences Research, Mayo Clinic, Rochester, MN; ∥∥∥Gastroenterology Division, Department of Internal Medicine and Comprehensive Cancer Center, and ¶¶¶Department of Surgery, School of Medicine, University of Michigan, Ann Arbor, MI; ###Cancer Biomarkers Research Group, Division of Cancer Prevention, National Cancer Institute, Rockville, MD; ****Departments of Surgery and Oncology, Kyushu University, Fukuoka, Japan; ††††Department of Medicine, Eastern Virginia Medical School, Norfolk, VA; and ‡‡‡‡Division of Oral Biology and Medicine, CLA School of Dentistry, Jonnson Comprehensive Cancer Center, University of California Los Angeles, L ·Pancreas · Pubmed #25931254.

ABSTRACT: Pancreatic cancer (PC) is estimated to become the second leading cause of cancer death in the United States by 2020. Early detection is the key to improving survival in PC. Addressing this urgent need, the Kenner Family Research Fund conducted the inaugural Early Detection of Sporadic Pancreatic Cancer Summit Conference in 2014 in conjunction with the 45th Anniversary Meeting of the American Pancreatic Association and Japan Pancreas Society. This seminal convening of international representatives from science, practice, and clinical research was designed to facilitate challenging interdisciplinary conversations to generate innovative ideas leading to the creation of a defined collaborative strategic pathway for the future of the field. An in-depth summary of current efforts in the field, analysis of gaps in specific areas of expertise, and challenges that exist in early detection is presented within distinct areas of inquiry: Case for Early Detection: Definitions, Detection, Survival, and Challenges; Biomarkers for Early Detection; Imaging; and Collaborative Studies. In addition, an overview of efforts in familial PC is presented in an addendum to this article. It is clear from the summit deliberations that only strategically designed collaboration among investigators, institutions, and funders will lead to significant progress in early detection of sporadic PC.

11 Review ACTH-secreting pancreatic neoplasms associated with Cushing syndrome: clinicopathologic study of 11 cases and review of the literature. 2015

Maragliano, Roberta / Vanoli, Alessandro / Albarello, Luca / Milione, Massimo / Basturk, Olca / Klimstra, David S / Wachtel, Antonio / Uccella, Silvia / Vicari, Emanuela / Milesi, Marina / Davì, Maria Vittoria / Scarpa, Aldo / Sessa, Fausto / Capella, Carlo / La Rosa, Stefano. ·*Department of Surgical and Morphological Sciences, University of Insubria, Varese, Italy ‡‡Department of Pathology, Ospedale di Circolo, Varese, Italy †Department of Molecular Medicine, University of Pavia, Pavia, Italy ‡Department of Pathology, San Raffaele Hospital, Milan, Italy §Department of Pathology, National Institute of Cancer, Milan, Italy #Department of Pathology, Multimedica, Milan, Italy **Department of Medicine, "G.B. Rossi" University Hospital, Verona, Italy ††ARC-NET Research Center and Department of Pathology and Diagnostics, University of Verona, Verona, Italy ∥Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY ¶Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru. ·Am J Surg Pathol · Pubmed #25353285.

ABSTRACT: Adrenocorticotropic hormone (ACTH)-secreting pancreatic neuroendocrine tumors (PanNETs), although rare, are responsible for about 15% of ectopic Cushing syndrome (CS). They represent a challenging entity because their preoperatory diagnosis is frequently difficult, and clear-cut morphologic criteria useful to differentiate them from other types of PanNETs have not been defined. Ectopic ACTH secretion associated with CS can also be rarely due to pancreatic acinar cell carcinoma (ACC) and pancreatoblastoma, rare tumor types with morphologic features sometimes overlapping those of PanNETs and, for this reason, representing a diagnostic challenge for pathologists. We herein describe the clinicopathologic and immunohistochemical features of 10 PanNETs and 1 ACC secreting ACTH and associated with CS together with an extensive review of the literature to give the reader a comprehensive overview on ACTH-producing pancreatic neoplasms. ACTH-secreting PanNETs are aggressive neoplasms with an immunohistochemical profile that partially overlaps that of pituitary corticotroph adenomas. They are generally large and well-differentiated neoplasms without distinctive histologic features but with signs of aggressiveness including vascular and perineural invasion. They are more frequent in female individuals with a mean age of 42 years. At 5 and 10 years after diagnosis, 35% and 16.2% of patients, respectively, were alive. ACTH-secreting ACCs and pancreatoblastomas are very aggressive pediatric tumors with a poor prognosis. Using an appropriate immunohistochemical panel including ACTH, β-endorphin, trypsin, and BCL10 it is possible to recognize ACTH-secreting PanNETs and to distinguish them from the very aggressive ACTH-secreting ACCs.

12 Review Adenocarcinoma of the pancreas. 2014

Hruban, Ralph H / Klimstra, David S. ·Department of Pathology, the Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Weinberg 2242, 401 N Broadway, Baltimore, Maryland 21231; Department of Oncology, the Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: rhruban@jhmi.edu. · Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York. ·Semin Diagn Pathol · Pubmed #25441308.

ABSTRACT: Infiltrating ductal adenocarcinoma of the pancreas is a real enigma. On one hand, it is one of the most deadly of all of the solid malignancies. On the other hand, the neoplastic glands can be remarkably well-differentiated, and it can be difficult to distinguish between a reactive non-neoplastic gland and a gland of invasive adenocarcinoma. In this review, we will present diagnostic criteria that one can "hang your hat on" when establishing the diagnosis of infiltrating ductal adenocarcinoma of the pancreas. We will also review clinically important features of the disease, and, with the impending incorporation of molecular genetics into everyday practice, we will emphasize clinical applications of cancer genetics.

13 Review Gastroenteropancreatic high-grade neuroendocrine carcinoma. 2014

Sorbye, Halfdan / Strosberg, Jonathan / Baudin, Eric / Klimstra, David S / Yao, James C. ·Department of Oncology, Haukeland University Hospital, Bergen, Norway. ·Cancer · Pubmed #24771552.

ABSTRACT: Gastroenteropancreatic (GEP) neuroendocrine neoplasms are classified as low-grade, intermediate-grade, and high-grade tumors based on morphologic criteria and the proliferation rate. Most studies have been conducted in patients with well differentiated (low-grade to intermediate-grade) neuroendocrine tumors. Data are substantially scarcer on poorly differentiated, high-grade neuroendocrine carcinoma (NEC), which includes the entities of small cell carcinoma and large cell NEC. A literature search of GEP-NEC was performed. Long-term survival was poor even among patients who presented with localized disease. Several studies highlighted heterogeneity within the high-grade NEC category and a need for the further identification of discreet prognostic and predictive groups. Tumors with a Ki-67 proliferation index <55% were less responsive to platinum-based chemotherapy, and patients with such tumors or with well differentiated morphology had better survival than patients who had tumors with poorly differentiated morphology or a higher Ki-67 index. Treatment options beyond platinum-based chemotherapy are emerging. A revision of the World Health Organization high-grade NEC classification seems to be necessary based on recent data. Platinum-based chemotherapy may not be the optimal treatment for patients who have GEP-NEC with a moderately high proliferation rate. Adequate diagnostic and prognostic stratifications constitute the basis for future progress.

14 Review Gastroenteropancreatic neuroendocrine neoplasms: historical context and current issues. 2013

Yang, Zhaohai / Tang, Laura H / Klimstra, David S. ·Department of Pathology, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania. ·Semin Diagn Pathol · Pubmed #24144288.

ABSTRACT: The digestive organs contain a large number of neuroendocrine cells as part of the diffuse neuroendocrine system. Neuroendocrine tumors can occur in every digestive organ. It has long been recognized that this is a diverse group of tumors with very different clinical outcomes; however, well-recognized prognostic parameters had been elusive until recently. Over the years, there have been several different classification schemes, each with different strengths and weaknesses. In an effort to standardize the classification and grading criteria for gastroenteropancreatic neuroendocrine tumors, the current World Health Organization classification includes a histologic grade based on proliferative rate (mitotic rate and Ki67 index) and a TNM stage that varies from organ to organ. The prognostic value of both the grade and stage has been validated in multiple studies. However, several issues remain, including the lack of standardized methods to assess proliferative rate, potential discrepancies between the mitotic count and the Ki67 index; intratumoral heterogeneity in proliferative rate; and the need for refinement in proliferative cut-points to define the grades. More studies are needed to further improve the classification of neuroendocrine tumors, thus guiding optimal treatment for these tumors.

15 Review Changing the way we do business: recommendations to accelerate biomarker development in pancreatic cancer. 2013

Tempero, Margaret A / Klimstra, David / Berlin, Jordan / Hollingsworth, Tony / Kim, Paula / Merchant, Nipun / Moore, Malcolm / Pleskow, Doug / Wang-Gillam, Andrea / Lowy, Andrew M. ·Pancreas Center, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA 94115, USA. mtempero@medicine.ucsf.edu ·Clin Cancer Res · Pubmed #23344262.

ABSTRACT: Pancreatic ductal adenocarcinoma is the most aggressive of all epithelial malignancies. In contrast to the favorable trends seen in most other common malignancies, the five-year survival of patients with this disease remains only 6%, a statistic that has changed minimally for decades. Only two drugs have been approved by the U.S. Food and Drug Administration (FDA) for use in pancreatic cancer in the last 15 years, and there are no established strategies for early detection.

16 Review Unusual DNA mismatch repair-deficient tumors in Lynch syndrome: a report of new cases and review of the literature. 2012

Karamurzin, Yevgeniy / Zeng, Zhaoshi / Stadler, Zsofia K / Zhang, Liying / Ouansafi, Ihsane / Al-Ahmadie, Hikmat A / Sempoux, Christine / Saltz, Leonard B / Soslow, Robert A / O'Reilly, Eileen M / Paty, Philip B / Coit, Daniel G / Shia, Jinru / Klimstra, David S. ·Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. ·Hum Pathol · Pubmed #22516243.

ABSTRACT: Immunohistochemical detection of DNA mismatch repair proteins and polymerase chain reaction detection of microsatellite instability have enhanced the recognition of mismatch repair-deficient neoplasms in patients with Lynch syndrome and, consequently, led to the identification of tumors that have not been included in the currently known Lynch syndrome tumor spectrum. Here, we report 4 such unusual tumors. Three of the 4, a peritoneal mesothelioma, a pancreatic acinar cell carcinoma, and a pancreatic well-differentiated neuroendocrine tumor, represented tumor types that, to the best of our knowledge, have not been previously reported in Lynch syndrome. The fourth tumor was an adrenocortical carcinoma, which has rarely been reported previously in Lynch syndrome. Three of our 4 patients carried a pathogenic germ-line mutation in a mismatch repair gene. The unusual tumor in each of the 3 patients showed loss of the mismatch repair protein corresponding to the mutation. The fourth patient did not have mutation information but had a history of colonic and endometrial carcinomas; both lacked MSH2 and MSH6 proteins. Interestingly, none of the 4 unusual tumors revealed microsatellite instability on polymerase chain reaction testing, whereas an appendiceal carcinoma from 1 of the study patients who was tested simultaneously did. The recognition of such tumors expands the repertoire of usable test samples for the workup of high-risk families. As yet, however, there are no data to support the inclusion of these tumors into general screening guidelines for detecting Lynch syndrome, nor are there data to warrant surveillance for these tumors in patients with Lynch syndrome.

17 Review Localized intrapancreatic malignant mesothelioma: a rare entity that may be confused with other pancreatic neoplasms. 2010

Espinal-Witter, Rosanny / Servais, Elliot L / Klimstra, David S / Lieberman, Michael D / Yantiss, Rhonda K. ·Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, 525 East 68th Street, New York, NY 10021, USA. roe2005@nyp.org. ·Virchows Arch · Pubmed #20148337.

ABSTRACT: Malignant mesothelioma usually presents with diffuse involvement of the pleura or peritoneum. Circumscribed or localized malignant mesothelioma has been described in these locations, as well as the viscera, in which case it may cause diagnostic confusion with other, more common entities. Herein, we describe the first well-documented case of primary intrapancreatic malignant mesothelioma in the English literature. The patient was an otherwise healthy 39-year-old woman who presented with a symptomatic mass in the head of the pancreas that was completely resected via pancreaticoduodenectomy. The tumor was composed of cysts, papillae, and tubules lined by cells with abundant eosinophilic cytoplasm and immunohistochemically expressed CA-125, calretinin, and D2-40. Follow-up revealed no evidence of residual or recurrent disease 32 months after surgery. This report also describes the clinical and pathologic characteristics of an intrapancreatic mesothelioma and provides a review of the literature regarding entities that may be considered in the differential diagnosis of this tumor.

18 Review An algorithmic approach to the diagnosis of pancreatic neoplasms. 2009

Klimstra, David S / Pitman, Martha B / Hruban, Ralph H. ·Department of Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065, USA. klimstrd@mskcc.org ·Arch Pathol Lab Med · Pubmed #19260750.

ABSTRACT: CONTEXT: The pancreas gives rise to an array of distinct neoplasms that can be solid, cystic, or intraductal and can recapitulate the various lines of differentiation present in the normal gland. OBJECTIVE: To develop an algorithmic approach to the diagnosis of pancreatic neoplasms that simplifies their pathologic evaluation. DATA SOURCES: We reviewed literature related to the classification of pancreatic neoplasms on the basis of their gross, histologic, and immunohistochemical features. CONCLUSIONS: By using a series of dichotomous decisions, the differential diagnosis of a pancreatic neoplasm can be narrowed, and in cases of the more common neoplasms, accurate classification can be achieved. Uncommon neoplasms not accounted for by this approach are also discussed, and the additional diagnostic information needed for complete pathologic reporting is presented.

19 Review Intraductal papillary mucinous neoplasms of the pancreas: clinical and pathological features and diagnostic approach. 2008

Katabi, N / Klimstra, D S. ·Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. klimstrd@mskcc.org ·J Clin Pathol · Pubmed #18703569.

ABSTRACT: Pancreatic intraductal papillary mucinous neoplasms (IPMNs) are mucin-producing neoplasms with a frequent papillary architecture that arise within the pancreatic ducts and are increasingly being recognised. Because they exhibit a spectrum of dysplasia ranging from low grade to high grade and may also have associated invasive carcinoma, and because they are clinically detectable, they are now intensively studied. There is marked overlap between IPMNs and pancreatic intraepithelial neoplasia (PanIN), such that the distinction between these two lesions is nearly impossible in certain cases. In addition, IPMNs sometimes can be confused with other primary cystic lesions of the pancreas. As a result, the correct diagnosis of IPMN can be challenging. This review addresses the clinical and pathological features of IPMNs, emphasising their diagnostic criteria, differential diagnosis and biological behaviour. Problematic issues in the pathological evaluation of IPMNs are discussed.

20 Clinical Trial A single-arm, nonrandomized phase II trial of neoadjuvant gemcitabine and oxaliplatin in patients with resectable pancreas adenocarcinoma. 2014

OʼReilly, Eileen M / Perelshteyn, Anna / Jarnagin, William R / Schattner, Mark / Gerdes, Hans / Capanu, Marinela / Tang, Laura H / LaValle, Joseph / Winston, Corinne / DeMatteo, Ronald P / DʼAngelica, Michael / Kurtz, Robert C / Abou-Alfa, Ghassan K / Klimstra, David S / Lowery, Maeve A / Brennan, Murray F / Coit, Daniel G / Reidy, Diane L / Kingham, T Peter / Allen, Peter J. ·*Gastrointestinal Oncology Service †Department of Medicine ‡Hepatopancreaticobiliary Surgery Service §Gastroenterology and Nutrition Service Departments of ¶Epidemiology and Biostatistics ‖Pathology **Radiology ††Surgery; and ‡‡Gastric and Mixed Tumor Service, Memorial Sloan-Kettering Cancer Center, New York, NY. ·Ann Surg · Pubmed #24901360.

ABSTRACT: BACKGROUND: The role for neoadjuvant systemic therapy in resectable pancreas adenocarcinoma remains undefined. OBJECTIVE: We evaluated the efficacy of gemcitabine and oxaliplatin administered as preoperative therapy in patients with resectable pancreas adenocarcinoma. METHODS: Eligible patients were screened using computed tomography-pancreas angiography, laparoscopy, endoscopic ultrasonography, and fine-needle aspiration cytology to identify 38 patients who received 4 cycles of neoadjuvant gemcitabine 1000 mg/m intravenously over 100 minutes and oxaliplatin 80 mg/m intravenously over 2 hours, every 2 weeks. Patients whose tumors remained resectable at restaging proceeded to operation and subsequently received 5 cycles of adjuvant gemcitabine (1000 mg/m intravenously over 30 minutes days 1, 8, and 15 every 4 weeks). The primary endpoint was 18-month overall survival and secondary endpoints included radiological, tumor marker and pathological response to neoadjuvant therapy, time to recurrence, patterns of failure, and feasibility of obtaining preoperative core biopsies. RESULTS: Thirty-five of 38 patients (92%) completed neoadjuvant therapy. Twenty-seven patients underwent tumor resection (resectability rate 71%), of which 26 initiated adjuvant therapy for a total of 23 patients (60.5%) who completed all planned therapy. The 18-month survival was 63% (24 patients alive). The median overall survival for all 38 patients was 27.2 months (95% confidence interval: 17-NA) and the median disease-specific survival was 30.6 months (95% confidence interval: 19-NA). CONCLUSIONS: This study met its endpoint and provided a signal suggesting that exploration of neoadjuvant systemic therapy is worthy of further investigation in resectable pancreas adenocarcinoma. Improved patient selection and more active systemic regimens are key. Clinical trials identification: NCT00536874.

21 Clinical Trial Survival after resection of pancreatic adenocarcinoma: results from a single institution over three decades. 2012

Winter, Jordan M / Brennan, Murray F / Tang, Laura H / D'Angelica, Michael I / Dematteo, Ronald P / Fong, Yuman / Klimstra, David S / Jarnagin, William R / Allen, Peter J. ·Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. winterj@mskcc.org ·Ann Surg Oncol · Pubmed #21761104.

ABSTRACT: BACKGROUND: Randomized trials have demonstrated a benefit associated with adjuvant therapy for pancreatic cancer, and retrospective studies have demonstrated improvements in postoperative mortality. The purpose of this study was to evaluate whether these improvements could be identified in a cohort of patients who underwent resection for pancreatic cancer at a single institution over three decades. METHODS: Short- (30 days), intermediate- (1 year), and long-term survival were compared between decades. Long-term survival focused on patients who survived at least 1 year to minimize the effects of perioperative mortality and patient selection. RESULTS: Between 1983 and 2009, 1147 pancreatic resections were performed for ductal adenocarcinoma, including 123 resections in the 1980s, 399 in the 1990s, and 625 in the 2000s. The 30-day mortality rates were 4.9%, 1.5% (P = 0.03 vs. 1980s), and 1.3% (P = 0.007 vs. 1980s). The 1-year mortality rates were 42%, 31% (P < 0.001 vs. 1980s), and 24% (P < 0.001 vs. 1980s and 1990s). In the group of patients who survived 1 year, the overall survivals were 23.2 months, 25.6 months (P = 0.6 vs. 1980s), and 24.5 months (P = 0.2 vs. 1980s). In a multivariate analysis adjusted for pathologic features, the decade of resection was not a significant predictor of long-term survival (hazard ratio = 1.1, P = 0.3). CONCLUSIONS: Patients who underwent resection for pancreatic cancer between 2000 and 2009 experienced improved operative mortality and 1-year survival compared to those who underwent resection in the 1980s, while the long-term survival was similar over all three decades. These results underscore the need for early detection strategies and more effective adjuvant therapies for patients with pancreatic cancer.

22 Article Precancerous neoplastic cells can move through the pancreatic ductal system. 2018

Makohon-Moore, Alvin P / Matsukuma, Karen / Zhang, Ming / Reiter, Johannes G / Gerold, Jeffrey M / Jiao, Yuchen / Sikkema, Lisa / Attiyeh, Marc A / Yachida, Shinichi / Sandone, Corinne / Hruban, Ralph H / Klimstra, David S / Papadopoulos, Nickolas / Nowak, Martin A / Kinzler, Kenneth W / Vogelstein, Bert / Iacobuzio-Donahue, Christine A. ·The David M. Rubenstein Center for Pancreatic Cancer Research, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Department of Pathology, University of California, Davis, Sacramento, CA, USA. · The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Canary Center for Cancer Early Detection, Department of Radiology, Stanford University School of Medicine, Palo Alto, CA, USA. · Program for Evolutionary Dynamics, Harvard University, Cambridge, MA, USA. · The Ludwig Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · VU University Amsterdam, Master's Oncology Program, VU University Medical Center, Amsterdam, The Netherlands. · Department of Cancer Genome Informatics, Graduate School of Medicine, Osaka University, Osaka, Japan. · Department of Art as Applied to Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Department of Mathematics, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA, USA. · Howard Hughes Medical Institute, The Johns Hopkins Kimmel Cancer Center, Baltimore, MD, USA. · The David M. Rubenstein Center for Pancreatic Cancer Research, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA. iacobuzc@mskcc.org. · Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. iacobuzc@mskcc.org. ·Nature · Pubmed #30177826.

ABSTRACT: Most adult carcinomas develop from noninvasive precursor lesions, a progression that is supported by genetic analysis. However, the evolutionary and genetic relationships among co-existing lesions are unclear. Here we analysed the somatic variants of pancreatic cancers and precursor lesions sampled from distinct regions of the same pancreas. After inferring evolutionary relationships, we found that the ancestral cell had initiated and clonally expanded to form one or more lesions, and that subsequent driver gene mutations eventually led to invasive pancreatic cancer. We estimate that this multi-step progression generally spans many years. These new data reframe the step-wise progression model of pancreatic cancer by illustrating that independent, high-grade pancreatic precursor lesions observed in a single pancreas often represent a single neoplasm that has colonized the ductal system, accumulating spatial and genetic divergence over time.

23 Article Hepatobiliary and Pancreatic: Primary acinar cell carcinoma of the liver showing good response to chemotherapy. 2018

Laino, M E / Ragucci, M / Klimstra, D S / Mannelli, L. ·Department of Radiology, Catholic University of the Sacred Heart, Rome, Italy. · Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · IRCCS SDN, Naples, Italy. · Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. ·J Gastroenterol Hepatol · Pubmed #29659083.

ABSTRACT: -- No abstract --

24 Article Progression Patterns in the Remnant Pancreas after Resection of Non-Invasive or Micro-Invasive Intraductal Papillary Mucinous Neoplasms (IPMN). 2018

Al Efishat, Mohammad / Attiyeh, Marc A / Eaton, Anne A / Gönen, Mithat / Basturk, Olca / Klimstra, David / D'Angelica, Michael I / DeMatteo, Ronald P / Kingham, T Peter / Balachandran, Vinod / Jarnagin, William R / Allen, Peter J. ·Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Department of Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA. allenp@mskcc.org. ·Ann Surg Oncol · Pubmed #29589164.

ABSTRACT: BACKGROUND: Although IPMN are thought to represent a whole-gland disease, segmental resection remains the most frequently performed treatment. We sought to determine the rates, patterns, and predictors of IPMN progression in the pancreatic remnant following segmental resection of noninvasive or microinvasive IPMN. METHODS: A prospectively maintained database was queried to identify all patients who underwent resection of noninvasive or microinvasive IPMN (≤ 10 mm of invasive component) between 1989 and 2015. Progression (recurrence) was defined as either the development of cancer, a new IPMN cystic lesion > 1 cm or ≥ 50% increase in the diameter of residual IPMN lesions in the remnant. Univariate and multivariate cox regression models were created to determine predictors of progression. RESULTS: A total of 319 patients underwent resection for noninvasive and microinvasive IPMN. The median age was 68, 53% had branch-duct (BD) IPMN, and 6% had microinvasive disease. After a median follow-up of 42 months, 71 patients (22%) experienced IPMN progression. Within this group of 71 patients, 11 (16% of recurrence) developed invasive cancer in the pancreatic remnant after a median of 28 months. Twelve patients (17%) experienced progression > 5 years following initial resection. On multivariate analysis, a distal location of the initial lesion was associated with an increased risk of progression (multivariate hazards ratio = 2.43, confidence interval 1.47-4.0, p < 0.001). CONCLUSIONS: In this study, 22% of patients had disease progression following resection of noninvasive or microinvasive IPMN; 16% of these progressions represented invasive disease. These patients represent a high-risk group and should undergo long-term radiographic surveillance.

25 Article Assessment of cytologic differentiation in high-grade pancreatic neuroendocrine neoplasms: A multi-institutional study. 2018

Sigel, Carlie S / Krauss Silva, Vitor Werneck / Reid, Michelle D / Chhieng, David / Basturk, Olca / Sigel, Keith M / Daniel, Tanisha D / Klimstra, David S / Tang, Laura H. ·Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York. · Department of Pathology, Emory University Hospital, Atlanta, Georgia. · Department of Pathology, University of Washington, Seattle, Washington. · Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York. ·Cancer Cytopathol · Pubmed #29044913.

ABSTRACT: BACKGROUND: Well-differentiated (WD) and poorly differentiated (PD) pancreatic neuroendocrine neoplasms are biologically distinct entities with different therapies and prognoses. WD neoplasms with elevated proliferation (Ki-67 > 20%) have been shown to have an overlapping histology with PD neuroendocrine carcinomas. This study compared expert cytomorphologic assessments of differentiation in pancreatic neuroendocrine neoplasms in a multi-institutional study. METHODS: Fine-needle aspiration specimens from pancreatic neuroendocrine neoplasms (grade 2 [G2] and grade 3 [G3] according to the 2017 World Health Organization classification; n = 72) were diagnosed independently by 3 cytopathologists as WD or PD (poorly differentiated large cell type [PD-L] or poorly differentiated small cell type [PD-S]) purely on the basis of cytomorphology. Their diagnoses were compared with a final classification supported by immunohistochemistry (retinoblastoma (RB), death domain- associated protein (DAXX), and α thalassemia/mental retardation syndrome X-linked (ATRX) protein expression), targeted mutation analysis (Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets), prior history of G1/G2 histology, and consensus. RESULTS: The rate of agreement on differentiation was 38% (15 WD cases and 12 PD cases) for the 70 cases included (55 WD cases [n = 19 G2, n = 31 G3, and n = 5 could not be graded] and 15 PD cases [n = 6 PD-S, n = 6 PD-L, and n = 3 PD, not otherwise specified). Two cases could not be classified by the employed methods. PD carcinomas had a higher rate of agreement (10 of 15 [67%]) than WD neoplasms (15 of 55 [27%]). Round nuclei and plasmacytoid cells were associated with agreement for WD cases, whereas apoptosis and angulated nuclei were associated with disagreement. Necrosis was associated with agreement for PD cases. CONCLUSIONS: A purely morphologic approach to the distinction between G2 and G3 pancreatic neuroendocrine neoplasms based on cytology can be challenging, with disagreement found among experienced cytopathologists. Cancer Cytopathol 2018;126:44-53. © 2017 American Cancer Society.

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