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Pancreatic Neoplasms: HELP
Articles by Sarah P. Thayer
Based on 47 articles published since 2009
(Why 47 articles?)
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Between 2009 and 2019, Sarah Thayer wrote the following 47 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Guideline Pancreatic Adenocarcinoma, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology. 2017

Tempero, Margaret A / Malafa, Mokenge P / Al-Hawary, Mahmoud / Asbun, Horacio / Bain, Andrew / Behrman, Stephen W / Benson, Al B / Binder, Ellen / Cardin, Dana B / Cha, Charles / Chiorean, E Gabriela / Chung, Vincent / Czito, Brian / Dillhoff, Mary / Dotan, Efrat / Ferrone, Cristina R / Hardacre, Jeffrey / Hawkins, William G / Herman, Joseph / Ko, Andrew H / Komanduri, Srinadh / Koong, Albert / LoConte, Noelle / Lowy, Andrew M / Moravek, Cassadie / Nakakura, Eric K / O'Reilly, Eileen M / Obando, Jorge / Reddy, Sushanth / Scaife, Courtney / Thayer, Sarah / Weekes, Colin D / Wolff, Robert A / Wolpin, Brian M / Burns, Jennifer / Darlow, Susan. · ·J Natl Compr Canc Netw · Pubmed #28784865.

ABSTRACT: Ductal adenocarcinoma and its variants account for most pancreatic malignancies. High-quality multiphase imaging can help to preoperatively distinguish between patients eligible for resection with curative intent and those with unresectable disease. Systemic therapy is used in the neoadjuvant or adjuvant pancreatic cancer setting, as well as in the management of locally advanced unresectable and metastatic disease. Clinical trials are critical for making progress in treatment of pancreatic cancer. The NCCN Guidelines for Pancreatic Adenocarcinoma focus on diagnosis and treatment with systemic therapy, radiation therapy, and surgical resection.

2 Guideline Pancreatic Adenocarcinoma, version 2.2012: featured updates to the NCCN Guidelines. 2012

Tempero, Margaret A / Arnoletti, J Pablo / Behrman, Stephen W / Ben-Josef, Edgar / Benson, Al B / Casper, Ephraim S / Cohen, Steven J / Czito, Brian / Ellenhorn, Joshua D I / Hawkins, William G / Herman, Joseph / Hoffman, John P / Ko, Andrew / Komanduri, Srinadh / Koong, Albert / Ma, Wen Wee / Malafa, Mokenge P / Merchant, Nipun B / Mulvihill, Sean J / Muscarella, Peter / Nakakura, Eric K / Obando, Jorge / Pitman, Martha B / Sasson, Aaron R / Tally, Anitra / Thayer, Sarah P / Whiting, Samuel / Wolff, Robert A / Wolpin, Brian M / Freedman-Cass, Deborah A / Shead, Dorothy A / Anonymous1061005. ·UCSF Helen Diller Family Comprehensive Cancer Center. ·J Natl Compr Canc Netw · Pubmed #22679115.

ABSTRACT: The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Pancreatic Adenocarcinoma discuss the workup and management of tumors of the exocrine pancreas. These NCCN Guidelines Insights provide a summary and explanation of major changes to the 2012 NCCN Guidelines for Pancreatic Adenocarcinoma. The panel made 3 significant updates to the guidelines: 1) more detail was added regarding multiphase CT techniques for diagnosis and staging of pancreatic cancer, and pancreas protocol MRI was added as an emerging alternative to CT; 2) the use of a fluoropyrimidine plus oxaliplatin (e.g., 5-FU/leucovorin/oxaliplatin or capecitabine/oxaliplatin) was added as an acceptable chemotherapy combination for patients with advanced or metastatic disease and good performance status as a category 2B recommendation; and 3) the panel developed new recommendations concerning surgical technique and pathologic analysis and reporting.

3 Guideline Pancreatic adenocarcinoma. 2010

Tempero, Margaret A / Arnoletti, J Pablo / Behrman, Stephen / Ben-Josef, Edgar / Benson, Al B / Berlin, Jordan D / Cameron, John L / Casper, Ephraim S / Cohen, Steven J / Duff, Michelle / Ellenhorn, Joshua D I / Hawkins, William G / Hoffman, John P / Kuvshinoff, Boris W / Malafa, Mokenge P / Muscarella, Peter / Nakakura, Eric K / Sasson, Aaron R / Thayer, Sarah P / Tyler, Douglas S / Warren, Robert S / Whiting, Samuel / Willett, Christopher / Wolff, Robert A / Anonymous3820673. · ·J Natl Compr Canc Netw · Pubmed #20876541.

ABSTRACT: -- No abstract --

4 Review Management of the Primary Tumor and Limited Metastases in Patients With Metastatic Pancreatic Cancer. 2015

Herman, Joseph M / Hoffman, John P / Thayer, Sarah P / Wolff, Robert A. · ·J Natl Compr Canc Netw · Pubmed #26158133.

ABSTRACT: New combinations of cytotoxic chemotherapy have been proven to increase response rates and survival times compared with single-agent gemcitabine for patients with metastatic pancreatic cancer. These responses have been dramatic for a subset of patients, therefore raising questions about the management of limited metastatic disease with surgery or other ablative methods. Similarly, for patients having a complete radiographic response to chemotherapy in the metastatic compartment, whether to consider local therapy in the form of radiation or surgery for the primary tumor is now an appropriate question. Therefore, collaboration among experts in surgery, medical oncology, and radiation oncology has led to the development of guiding principles for local therapies to the primary intact pancreatic tumor for patients with limited metastatic disease and those who have had a significant response after systemic therapy.

5 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.

6 Review Intraductal papillary mucinous neoplasms: does a family history of pancreatic cancer matter? 2012

Nehra, Deepika / Oyarvide, Vicente Morales / Mino-Kenudson, Mari / Thayer, Sarah P / Ferrone, Cristina R / Wargo, Jennifer A / Muzikansky, Alona / Finkelstein, Dianne / Warshaw, Andrew L / Castillo, Carlos Fernández-del. ·Department of Surgery, Massachusetts General Hospital, Boston MA, USA. ·Pancreatology · Pubmed #22898638.

ABSTRACT: BACKGROUND/OBJECTIVES: The purpose of this study is to compare surgically resected intraductal papillary mucinous neoplasms (IPMNs) in patients with and without a family history of pancreatic cancer to gain insight into differences that may suggest the need for differential management. METHODS: A retrospective review of patients who underwent resection of an IPMN at the Massachusetts General Hospital (1990-2011) was conducted. Three hundred and twenty-four patients of whom 45 (13.9%) had a family history of pancreatic cancer were identified. Patients with (PFH) and without (NFH) a family history of pancreatic cancer were compared. RESULTS: There were no differences in demographic characteristics between groups. Extra-pancreatic malignancies diagnosed prior to the IPMN were more common in those with a PFH (35.6% vs 20.1%, p = 0.03). There were no differences in IPMN characteristics between groups including no difference in the presence of invasive disease (p = 0.55). Concurrent pancreatic ductal adenocarcinomas were more common in those with a PFH (11.1% vs 2.9%, p = 0.02). The survival in the PFH group was marginally lower than the NFH group, a difference found to be attributable to the higher prevalence of extra-pancreatic malignancies. CONCLUSION: Characteristics of surgically resected IPMNs are not different between patients with and without a family history of pancreatic cancer. Most importantly, the incidence of invasive disease is not different, suggesting that these lesions may not be more aggressive when they occur in the presence of a family history of pancreatic cancer.

7 Review Sonic Hedgehog in pancreatic cancer: from bench to bedside, then back to the bench. 2012

Rosow, David E / Liss, Andrew S / Strobel, Oliver / Fritz, Stefan / Bausch, Dirk / Valsangkar, Nakul P / Alsina, Janivette / Kulemann, Birte / Park, Joo Kyung / Yamaguchi, Junpei / LaFemina, Jennifer / Thayer, Sarah P. ·Pancreatic Biology Laboratory, Department of Surgery, Massachusetts General Hospital, Boston, MA, USA. ·Surgery · Pubmed #22770959.

ABSTRACT: -- No abstract --

8 Review Management of mucin-producing cystic neoplasms of the pancreas. 2009

Fritz, Stefan / Warshaw, Andrew L / Thayer, Sarah P. ·Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA. ·Oncologist · Pubmed #19211618.

ABSTRACT: During the last decade small lesions of the pancreas have been increasingly recognized in clinical practice. Among these lesions, mucin-producing cystic neoplasms represent a recently described and unique entity among pancreatic tumors. In 1996, the World Health Organization distinguished two different types of mucinous cystic tumors: intraductal papillary mucinous neoplasms (IPMNs) of the pancreas, which are characterized by mucin production, cystic dilation of the pancreatic ducts, and intrapapillary growth, and mucinous cystic neoplasms (MCNs), which are defined by ovarian-like stroma and in most cases do not communicate with pancreatic ducts. Further, IPMNs can be subdivided into main-duct type, mixed-type, and branch-duct type tumors. Older data did not distinguish among different subsets of cystic neoplasms of the pancreas, and consequently many databases were inconsistent. Histopathologically, both IPMNs and MCNs demonstrate a wide spectrum of cellular atypia ranging from mild mucinous hyperplasia to invasive adenocarcinoma. Because mucinous cystic neoplasms of the pancreas show significant differences in clinical behavior from patient to patient, knowledge of the clinicopathologic characteristics and natural history of specific subtypes of IPMNs and MCNs has become crucial for physicians working in the field of gastroenterology. The present work offers an overview of current and generally accepted clinical guidelines for the diagnosis and treatment of IPMNs and MCNs.

9 Clinical Trial Circulating tumor cells found in patients with localized and advanced pancreatic cancer. 2015

Kulemann, Birte / Pitman, Martha B / Liss, Andrew S / Valsangkar, Nakul / Fernández-Del Castillo, Carlos / Lillemoe, Keith D / Hoeppner, Jens / Mino-Kenudson, Mari / Warshaw, Andrew L / Thayer, Sarah P. ·From the *Department of Surgery and †Andrew L. Warshaw Institute for Pancreatic Cancer Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA; ‡Department of Surgery, University Hospital Freiburg, Freiburg, Germany; §Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA; and ║Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE. ·Pancreas · Pubmed #25822154.

ABSTRACT: OBJECTIVES: Isolation of circulating tumor cells (CTCs) holds the promise of diagnosing and molecular profiling cancers from a blood sample. Here, we test a simple new low-cost filtration device for CTC isolation in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: Peripheral blood samples drawn from healthy donors and PDAC patients were filtered using ScreenCell devices, designed to capture CTCs for cytologic and molecular analysis. Giemsa-stained specimens were evaluated by a pancreatic cytopathologist blinded to the histological diagnosis. Circulating tumor cell DNA was subjected to KRAS mutational analysis. RESULTS: Spiking experiments demonstrated a CTC capture efficiency as low as 2 cells/mL of blood. Circulating tumor cells were identified by either malignant cytology or presence of KRAS mutation in 73% of 11 patients (P = 0.001). Circulating tumor cells were identified in 3 of 4 patients with early (≤American Joint Committee on Cancer stage IIB) and in 5 of 7 patients with advanced (≥ American Joint Committee on Cancer stage III) PDAC. No CTCs were detected in blood from 9 health donors. CONCLUSIONS: Circulating tumor cells can be found in most patients with PDAC of any stage, whether localized, locally advanced, or metastatic. The ability to capture, cytologically identify, and genetically analyze CTCs suggests a possible tool for the diagnosis and characterization of genetic alterations of PDAC.

10 Article Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine. 2017

Geller, Leore T / Barzily-Rokni, Michal / Danino, Tal / Jonas, Oliver H / Shental, Noam / Nejman, Deborah / Gavert, Nancy / Zwang, Yaara / Cooper, Zachary A / Shee, Kevin / Thaiss, Christoph A / Reuben, Alexandre / Livny, Jonathan / Avraham, Roi / Frederick, Dennie T / Ligorio, Matteo / Chatman, Kelly / Johnston, Stephen E / Mosher, Carrie M / Brandis, Alexander / Fuks, Garold / Gurbatri, Candice / Gopalakrishnan, Vancheswaran / Kim, Michael / Hurd, Mark W / Katz, Matthew / Fleming, Jason / Maitra, Anirban / Smith, David A / Skalak, Matt / Bu, Jeffrey / Michaud, Monia / Trauger, Sunia A / Barshack, Iris / Golan, Talia / Sandbank, Judith / Flaherty, Keith T / Mandinova, Anna / Garrett, Wendy S / Thayer, Sarah P / Ferrone, Cristina R / Huttenhower, Curtis / Bhatia, Sangeeta N / Gevers, Dirk / Wargo, Jennifer A / Golub, Todd R / Straussman, Ravid. ·Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. · Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. · Institute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA. · Department of Radiology, Brigham and Women's Hospital, Boston, MA 02115, USA. · Joint Center for Cancer Precision Medicine, Dana-Farber Cancer Institute, Boston, MA 02215, USA. · Department of Mathematics and Computer Science, Open University of Israel, Raanana, Israel. · Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. · Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. · Department of Immunology, Weizmann Institute of Science, Rehovot, Israel. · Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel. · Department of Surgical Oncology, Massachusetts General Hospital, Boston, MA 02114, USA. · Massachusetts General Hospital Cancer Center, Boston, MA 02114, USA. · Small Molecule Mass Spectrometry Facility, Faculty of Arts and Sciences Division of Science, Harvard University, Cambridge, MA 02138, USA. · Life Sciences Core Facilities, Weizmann Institute of Science, Rehovot, Israel. · Department of Physics of Complex Systems, Weizmann Institute of Science, Rehovot, Israel. · Department of Biomedical Engineering, Columbia University, New York City, NY 10027, USA. · Ahmed Center for Pancreatic Cancer Research, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. · Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. · Harvard T. H. Chan School of Public Health, Departments of Immunology and Infectious Diseases and Genetics and Complex Diseases, Boston, MA 02115, USA. · Department of Pathology, Sheba Medical Center, Ramat Gan, Israel. · Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. · Department of Oncology, Sheba Medical Center, Ramat Gan, Israel. · Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA. · Dana-Farber Cancer Institute, Boston, MA 02115, USA. · Department of Surgery, University of Nebraska Medical Center, Omaha, NE 68198-6345, USA. · Pancreas and Biliary Surgery Program, Massachusetts General Hospital, Boston, MA 02114, USA. · Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115, USA. · Harvard-MIT Division of Health Sciences and Technology, MIT, Cambridge, MA 02139, USA. · Howard Hughes Medical Institute (HHMI), Institute for Medical Engineering and Science, MIT, Cambridge, MA 02139, USA. · Division of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. · Department of Electrical Engineering and Computer Science, MIT, Cambridge, MA 02139, USA. · Ludwig Center for Molecular Oncology, MIT, Cambridge, MA 02139, USA. · Marble Center for Cancer Nanomedicine, MIT, Cambridge, MA 02139, USA. · HHMI, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. · Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. · Harvard Medical School, Boston, MA 02115, USA. · Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. ravidst@weizmann.ac.il. ·Science · Pubmed #28912244.

ABSTRACT: Growing evidence suggests that microbes can influence the efficacy of cancer therapies. By studying colon cancer models, we found that bacteria can metabolize the chemotherapeutic drug gemcitabine (2',2'-difluorodeoxycytidine) into its inactive form, 2',2'-difluorodeoxyuridine. Metabolism was dependent on the expression of a long isoform of the bacterial enzyme cytidine deaminase (CDD

11 Article Tumor engraftment in patient-derived xenografts of pancreatic ductal adenocarcinoma is associated with adverse clinicopathological features and poor survival. 2017

Pergolini, Ilaria / Morales-Oyarvide, Vicente / Mino-Kenudson, Mari / Honselmann, Kim C / Rosenbaum, Matthew W / Nahar, Sabikun / Kem, Marina / Ferrone, Cristina R / Lillemoe, Keith D / Bardeesy, Nabeel / Ryan, David P / Thayer, Sarah P / Warshaw, Andrew L / Fernández-Del Castillo, Carlos / Liss, Andrew S. ·Department of Surgery and the Andrew L. Warshaw, MD Institute for Pancreatic Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America. · Department of Surgery, Universita' Politecnica delle Marche, Ancona, Italy. · Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America. · Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts, United States of America. ·PLoS One · Pubmed #28854237.

ABSTRACT: Patient-derived xenograft (PDX) tumors are powerful tools to study cancer biology. However, the ability of PDX tumors to model the biological and histological diversity of pancreatic ductal adenocarcinoma (PDAC) is not well known. In this study, we subcutaneously implanted 133 primary and metastatic PDAC tumors into immunodeficient mice. Fifty-seven tumors were successfully engrafted and even after extensive passaging, the histology of poorly-, moderately-, and well-differentiated tumors was maintained in the PDX models. Moreover, the fibroblast and collagen contents in the stroma of patient tumors were recapitulated in the corresponding PDX models. Analysis of the clinicopathological features of patients revealed xenograft tumor engraftment was associated with lymphovascular invasion (P = 0.001) and worse recurrence-free (median, 7 vs. 16 months, log-rank P = 0.047) and overall survival (median, 13 vs. 21 months, log-rank P = 0.038). Among successful engraftments, median time of growth required for reimplantation into new mice was 151 days. Reflective of the inherent biological diversity between PDX tumors with rapid (<151 days) and slow growth, differences in their growth were maintained during extensive passaging. Rapid growth was additionally associated with lymph node metastasis (P = 0.022). The association of lymphovascular invasion and lymph node metastasis with PDX formation and rapid growth may reflect an underlying biological mechanism that allows these tumors to adapt and grow in a new environment. While the ability of PDX tumors to mimic the cellular and non-cellular features of the parental tumor stroma provides a valuable model to study the interaction of PDAC cells with the tumor microenvironment, the association of successful engraftment with adverse clinicopathological features suggests PDX models over represent more aggressive forms of this disease.

12 Article Cytologic characteristics of circulating epithelioid cells in pancreatic disease. 2017

Rosenbaum, Matthew W / Cauley, Christy E / Kulemann, Birte / Liss, Andrew S / Castillo, Carlos Fernandez-Del / Warshaw, Andrew L / Lillemoe, Keith D / Thayer, Sarah P / Pitman, Martha B. ·Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts. · Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts. · Department of Surgery, University Hospital Freiburg, Freiburg, Germany. · Division of Surgical Oncology, Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska. ·Cancer Cytopathol · Pubmed #28257167.

ABSTRACT: BACKGROUND: Circulating epithelioid cells (CECs), also known as circulating tumor, circulating cancer, circulating epithelial, or circulating nonhematologic cells, are a prognostic factor in various malignancies that can be isolated via various protocols. In the current study, the authors analyzed the cytomorphologic characteristics of CECs isolated by size in a cohort of patients with benign and malignant pancreatic diseases to determine whether cytomorphological features could predict CEC origin. METHODS: Blood samples were collected from 9 healthy controls and 171 patients with pancreatic disease who were presenting for surgical evaluation before treatment. Blood was processed with the ScreenCell size-based filtration device. Evaluable CECs were analyzed in a blinded fashion for cytomorphologic characteristics, including cellularity; nucleoli; nuclear size, irregularity, variability, and hyperchromasia; and nuclear-to-cytoplasmic ratio. Statistical differences between variables were analyzed via the Fisher exact test. RESULTS: No CECs were identified among the 9 normal healthy controls. Of the 115 patients with CECs (positive or suspicious for), 25 had nonmalignant disease and 90 had malignancy. There were no significant differences in any of the cytologic criteria noted between groups divided by benign versus malignant, neoplastic versus nonneoplastic, or pancreatic ductal adenocarcinoma versus neuroendocrine tumor. CONCLUSIONS: CECs were observed in patients with malignant and nonmalignant pancreatic disease, but not in healthy controls. There were no morphologic differences observed between cells from different pancreatic diseases, suggesting that numerous conditions may be associated with CECs in the circulation and that care must be taken not to overinterpret cells identified by cytomorphology as indicative of circulating tumor cells of pancreatic cancer. Additional studies are required to determine the origin and clinical significance of these cells. Cancer Cytopathol 2017;125:332-340. © 2017 American Cancer Society.

13 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.

14 Article Loss of Trefoil Factor 2 From Pancreatic Duct Glands Promotes Formation of Intraductal Papillary Mucinous Neoplasms in Mice. 2016

Yamaguchi, Junpei / Mino-Kenudson, Mari / Liss, Andrew S / Chowdhury, Sanjib / Wang, Timothy C / Fernández-Del Castillo, Carlos / Lillemoe, Keith D / Warshaw, Andrew L / Thayer, Sarah P. ·Department of Surgery, Andrew L. Warshaw Institute for Pancreatic Cancer Research, Massachusetts General Hospital, Boston, Massachusetts. · Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts. · Division of Surgical Oncology and the Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, Nebraska. · Division of Digestive and Liver Diseases and Irving Cancer Research Center, Columbia University Medical Center, New York, New York. · Department of Surgery, Andrew L. Warshaw Institute for Pancreatic Cancer Research, Massachusetts General Hospital, Boston, Massachusetts; Division of Surgical Oncology and the Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, Nebraska. Electronic address: sarah.thayer@unmc.edu. ·Gastroenterology · Pubmed #27523981.

ABSTRACT: BACKGROUND & AIMS: Little is known about the origin of pancreatic intraductal papillary mucinous neoplasms (IPMN). Pancreatic duct glands (PDGs) are gland-like outpouches budding off the main pancreatic ducts that function as a progenitor niche for the ductal epithelium; they express gastric mucins and have characteristics of side-branch IPMNs. We investigated whether PDGs are a precursor compartment for IPMNs and the role of Trefoil factor family 2 (TFF2)-a protein expressed by PDGs and the gastric mucosa that are involved in epithelial repair and tumor suppression. METHODS: We obtained pancreatectomy specimens from 20 patients with chronic pancreatitis, 13 with low-grade side-branch IPMNs, and 15 patients with PDAC; histologically normal pancreata were used as controls (n = 18). Samples were analyzed by immunohistochemistry to detect TFF1 and TFF2 and cell proliferation. We performed mitochondrial DNA mutational mapping studies to determine the cell lineage and fate of PDG cells. Pdx1-Cre;LSL-KRAS RESULTS: Histologic analysis of human samples revealed gastric-type IPMN to comprise 2 molecularly distinct layers: a basal crypt segment that expressed TFF2 and overlying papillary projections. Proliferation occurred predominantly in the PDG-containing basal segments. Mitochondrial mutation mapping revealed a 97% match between the profiles of proliferating PDG cells and their overlying nonproliferative IPMN cells. In contrast to KC mice, 2-month-old KC/Tff2 CONCLUSIONS: In histologic analyses of human IPMNs, we found PDGs to form the basal segment and possibly serve as a progenitor compartment. TFF2 has tumor-suppressor activity in the mouse pancreas and prevents formation of mucinous neoplasms.

15 Article Regulation of GLI Underlies a Role for BET Bromodomains in Pancreatic Cancer Growth and the Tumor Microenvironment. 2016

Huang, Yinshi / Nahar, Sabikun / Nakagawa, Akifumi / Fernandez-Barrena, Maite G / Mertz, Jennifer A / Bryant, Barbara M / Adams, Curtis E / Mino-Kenudson, Mari / Von Alt, Kate N / Chang, Kevin / Conery, Andrew R / Hatton, Charlie / Sims, Robert J / Fernandez-Zapico, Martin E / Wang, Xingpeng / Lillemoe, Keith D / Fernández-Del Castillo, Carlos / Warshaw, Andrew L / Thayer, Sarah P / Liss, Andrew S. ·Departments of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, P.R. China. Department of Surgery and the Andrew L. Warshaw, MD, Institute for Pancreatic Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. · Department of Surgery and the Andrew L. Warshaw, MD, Institute for Pancreatic Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. · Division of Oncology Research, Schulze Center for Novel Therapeutics, Mayo Clinic, Rochester, Minnesota. · Constellation Pharmaceuticals, Cambridge, Massachusetts. · Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. · Departments of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, P.R. China. Departments of Gastroenterology, Shanghai First People's Hospital, Shanghai Jiatong University School of Medicine, Shanghai, P.R. China. · Department of Surgery and the Andrew L. Warshaw, MD, Institute for Pancreatic Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. aliss@mgh.harvard.edu sarah.thayer@unmc.edu. ·Clin Cancer Res · Pubmed #27169995.

ABSTRACT: PURPOSE: The initiation, progression, and maintenance of pancreatic ductal adenocarcinoma (PDAC) results from the interplay of genetic and epigenetic events. While the genetic alterations of PDAC have been well characterized, epigenetic pathways regulating PDAC remain, for the most part, elusive. The goal of this study was to identify novel epigenetic regulators contributing to the biology of PDAC. EXPERIMENTAL DESIGN: In vivo pooled shRNA screens targeting 118 epigenetic proteins were performed in two orthotopic PDAC xenograft models. Candidate genes were characterized in 19 human PDAC cell lines, heterotopic xenograft tumor models, and a genetically engineered mouse (GEM) model of PDAC. Gene expression, IHC, and immunoprecipitation experiments were performed to analyze the pathways by which candidate genes contribute to PDAC. RESULTS: In vivo shRNA screens identified BRD2 and BRD3, members of the BET family of chromatin adaptors, as key regulators of PDAC tumor growth. Pharmacologic inhibition of BET bromodomains enhanced survival in a PDAC GEM model and inhibited growth of human-derived xenograft tumors. BET proteins contribute to PDAC cell growth through direct interaction with members of the GLI family of transcription factors and modulating their activity. Within cancer cells, BET bromodomain inhibition results in downregulation of SHH, a key mediator of the tumor microenvironment and canonical activator of GLI. Consistent with this, inhibition of BET bromodomains decreases cancer-associated fibroblast content of tumors in both GEM and xenograft tumor models. CONCLUSIONS: Therapeutic inhibition of BET proteins offers a novel mechanism to target both the neoplastic and stromal components of PDAC. Clin Cancer Res; 22(16); 4259-70. ©2016 AACR.

16 Article Circulating Epithelial Cells in Patients with Pancreatic Lesions: Clinical and Pathologic Findings. 2015

Cauley, Christy E / Pitman, Martha B / Zhou, Jiahua / Perkins, James / Kuleman, Birte / Liss, Andrew S / Fernandez-Del Castillo, Carlos / Warshaw, Andrew L / Lillemoe, Keith D / Thayer, Sarah P. ·Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA; Warshaw Institute for Pancreatic Cancer Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA. Electronic address: ccauley@partners.org. · Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA. · Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA; Warshaw Institute for Pancreatic Cancer Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA. · Division of Surgical Oncology, Department of Surgery, University of Nebraska Medical Center, Omaha, NE. ·J Am Coll Surg · Pubmed #26209458.

ABSTRACT: BACKGROUND: Circulating epithelial cell (CEC) isolation has provided diagnostic and prognostic information for a variety of cancers, previously supporting their identity as circulating tumor cells in the literature. However, we report CEC findings in patients with benign, premalignant, and malignant pancreatic lesions using a size-selective filtration device. STUDY DESIGN: Peripheral blood samples were drawn from patients found to have pancreatic lesions on preoperative imaging at a surgical clinic. Blood was filtered using ScreenCell devices, which were evaluated microscopically by a pancreatic cytopathologist. Pathologic data and clinical outcomes of these patients were obtained from medical records during a 1-year follow-up period. RESULTS: Nine healthy volunteers formed the control group and were found to be negative for CECs. There were 179 patients with pancreatic lesions that formed the study cohort. Circulating epithelial cells were morphologically similar in patients with a variety of pancreatic lesions. Specifically, CECs were identified in 51 of 105 pancreatic ductal adenocarcinomas (49%), 7 of 11 neuroendocrine tumors (64%), 13 of 21 intraductal papillary mucinous neoplasms (62%), and 6 of 13 patients with chronic pancreatitis. Rates of CEC identification were similar in patients with benign, premalignant, and malignant lesions (p = 0.41). In addition, CEC findings in pancreatic ductal adenocarcinoma patients were not associated with poor prognosis. CONCLUSIONS: Although CECs were not identified in healthy volunteers, they were identified in patients with benign, premalignant, and malignant pancreatic lesions. The presence of CECs in patients presenting with pancreatic lesions is neither diagnostic of malignancy nor prognostic for patients with pancreatic ductal adenocarcinoma.

17 Article IPMN involving the main pancreatic duct: biology, epidemiology, and long-term outcomes following resection. 2015

Marchegiani, Giovanni / Mino-Kenudson, Mari / Sahora, Klaus / Morales-Oyarvide, Vicente / Thayer, Sarah / Ferrone, Cristina / Warshaw, Andrew L / Lillemoe, Keith D / Fernández-Del Castillo, Carlos. ·Departments of *Surgery; and †Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA. ·Ann Surg · Pubmed #24979607.

ABSTRACT: OBJECTIVES: To describe the characteristics of intraductal papillary mucinous neoplasms (IPMNs) with predominant involvement of the main pancreatic duct (MPD), analyzing predictors for survival and recurrence. BACKGROUND: IPMNs involving the MPD harbor a high likelihood of malignancy and different biological features. The appropriateness of including cases with minimal noncircumferential MPD involvement has been challenged because these show clinicopathological features that are similar to branch duct IPMN. Accordingly, their exclusion has led to a redefinition of MPD IPMN (MD-IPMN). METHODS: Retrospective review of resected MD-IPMN from 1990 to 2013. All slides were reviewed by a single pancreatic pathologist and classified on the basis of epithelial type and invasive component. RESULTS: A total of 223 patients underwent resection for IPMN involving the MPD. Of these, 50 were excluded because of minimal MPD involvement. Among the 173 patients analyzed, median age was 68 years and 55% were males. Predominant epithelial phenotype was intestinal (50%). Forty-eight patients (28%) had low- or intermediate-grade dysplasia, whereas 125 (72%) had either high-grade dysplasia (33%) or invasive carcinoma (39%). Of the 67 invasive IPMNs, 39 were tubular carcinomas (58%) and invasion was minimal (<5 mm) in 28 (42%). The 5-year overall survival rate was 69% and the disease-specific survival rate was 83%. The estimated recurrence rate at 10 years was 25%. Size and type of the invasive component, lymph node positivity, and a positive resection margin were predictors for both survival and recurrence (P < 0.05). CONCLUSIONS: MD-IPMN is mainly intestinal-type and malignant. After resection, it has a very favorable prognosis, especially in the absence of macroscopic invasive carcinoma.

18 Article Pancreatic adenocarcinoma, version 2.2014: featured updates to the NCCN guidelines. 2014

Tempero, Margaret A / Malafa, Mokenge P / Behrman, Stephen W / Benson, Al B / Casper, Ephraim S / Chiorean, E Gabriela / Chung, Vincent / Cohen, Steven J / Czito, Brian / Engebretson, Anitra / Feng, Mary / Hawkins, William G / Herman, Joseph / Hoffman, John P / Ko, Andrew / Komanduri, Srinadh / Koong, Albert / Lowy, Andrew M / Ma, Wen Wee / Merchant, Nipun B / Mulvihill, Sean J / Muscarella, Peter / Nakakura, Eric K / Obando, Jorge / Pitman, Martha B / Reddy, Sushanth / Sasson, Aaron R / Thayer, Sarah P / Weekes, Colin D / Wolff, Robert A / Wolpin, Brian M / Burns, Jennifer L / Freedman-Cass, Deborah A. ·From UCSF Helen Diller Family Comprehensive Cancer Center; Moffitt Cancer Center; St. Jude Children's Research Hospital/The University of Tennessee Health Science Center; Robert H. Lurie Comprehensive Cancer Center of Northwestern University; Memorial Sloan Kettering Cancer Center; Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance; City of Hope Comprehensive Cancer Center; Fox Chase Cancer Center; Duke Cancer Institute; Pancreatic Cancer Action Network (PanCAN); University of Michigan Comprehensive Cancer Center; Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; Stanford Cancer Institute; UC San Diego Moores Cancer Center; Roswell Park Cancer Institute; Vanderbilt-Ingram Cancer Center; Huntsman Cancer Institute at the University of Utah; The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute; Massachusetts General Hospital Cancer Center; University of Alabama at Birmingham Comprehensive Cancer Center; Fred & Pamela Buffett Cancer Center at The Nebraska Medical Center; University of Colorado Cancer Center; The University of Texas MD Anderson Cancer Center; Dana-Farber/Brigham and Women's Cancer Center; and National Comprehensive Cancer Network. ·J Natl Compr Canc Netw · Pubmed #25099441.

ABSTRACT: The NCCN Guidelines for Pancreatic Adenocarcinoma discuss the diagnosis and management of adenocarcinomas of the exocrine pancreas and are intended to assist with clinical decision-making. These NCCN Guidelines Insights summarize major discussion points from the 2014 NCCN Pancreatic Adenocarcinoma Panel meeting. The panel discussion focused mainly on the management of borderline resectable and locally advanced disease. In particular, the panel discussed the definition of borderline resectable disease, role of neoadjuvant therapy in borderline disease, role of chemoradiation in locally advanced disease, and potential role of newer, more active chemotherapy regimens in both settings.

19 Article High performing whipple patients: factors associated with short length of stay after open pancreaticoduodenectomy. 2014

Lee, Grace C / Fong, Zhi Ven / Ferrone, Cristina R / Thayer, Sarah P / Warshaw, Andrew L / Lillemoe, Keith D / Fernández-del Castillo, Carlos. ·Department of Surgery, Massachusetts General Hospital, Harvard Medical School, 15 Parkman Street, Boston, MA, 02114-3117, USA. ·J Gastrointest Surg · Pubmed #25091843.

ABSTRACT: INTRODUCTION: Despite the decreasing mortality of pancreaticoduodenectomy (PD), it continues to be associated with prolonged length of postoperative hospital stay (LOS). This study aimed to determine factors that could predict short LOS after PD. Additionally, as preliminary data of minimally invasive PD emerges, we sought to determine the average LOS after open PD at a high-volume center to set a standard to which minimally invasive PD can be compared. METHODS: A total of 634 consecutive patients who underwent open PD between January 2007 and December 2012 at the Massachusetts General Hospital comprised the study cohort. "High performers" were defined as patients with postoperative LOS ≤5 days. RESULTS: Median LOS was 7 days. A total of 61 patients (9.6%) had LOS ≤5 days and were deemed "high performing." In multivariate logistic regression analysis, male gender (p = 0.032), neoadjuvant chemoradiation (p = 0.001), epidural success (p = 0.019), epidural duration ≤3 days (p = 0.001), lack of complications (p < 0.001), surgery on Thursday or Friday (p = 0.001), and discharge on Monday through Wednesday (p < 0.001) were independently associated with LOS ≤5 days. Readmission rate, time to readmission, and mortality were not different between the two groups. The proportion of patients with pancreatic ductal adenocarcinoma who went on to receive adjuvant therapy was no different if LOS was ≤5 or >5 days, but high performance was predictive of beginning therapy <8 weeks after surgery (p = 0.010). CONCLUSION: In our experience, median LOS was 7 days, and early discharge (≤5 days) after open PD is safe and feasible in about 10 % of patients. These high performers are more likely to be male, have received neoadjuvant therapy, and had successful epidural analgesia. High performers with cancer are more likely to start chemotherapy <8 weeks after surgery. Minimally invasive PD should be compared to this high standard for median LOS, among other quality metrics, to justify its increased cost, operative duration, and learning curve.

20 Article Not all mixed-type intraductal papillary mucinous neoplasms behave like main-duct lesions: implications of minimal involvement of the main pancreatic duct. 2014

Sahora, Klaus / Fernández-del Castillo, Carlos / Dong, Fei / Marchegiani, Giovanni / Thayer, Sarah P / Ferrone, Cristina R / Sahani, Dushyant V / Brugge, William R / Warshaw, Andrew L / Lillemoe, Keith D / Mino-Kenudson, Mari. ·Department of Surgery, Massachusetts General Hospital, Boston, MA; Department of Surgery, Harvard Medical School, Boston, MA. · Department of Pathology, Massachusetts General Hospital, Boston, MA. · Department of Radiology, Massachusetts General Hospital, Boston, MA; Department of Radiology, Harvard Medical School, Boston, MA. · Division of Gastroenterology, Massachusetts General Hospital, Boston, MA; Department of Internal Medicine, Harvard Medical School, Boston, MA. · Department of Pathology, Massachusetts General Hospital, Boston, MA; Department of Pathology, Harvard Medical School, Boston, MA. Electronic address: mminokenudson@partners.org. ·Surgery · Pubmed #25081232.

ABSTRACT: BACKGROUND: The malignant potential of intraductal mucinous neoplasm of the pancreas (IPMN) is associated closely with main pancreatic duct (MPD) involvement. Because mixed-type IPMN is thought to have the same malignant potential as that of main-duct (MD)-IPMN, resection is recommended; however, the biological nature of mixed-type IPMN with only minimal involvement of MPD (min-mix-IPMN) may be different. METHODS: A prospective database of 404 resected IPMNs was re-reviewed to subclassify mixed-type IPMNs. We defined min-mix-IPMN as absence of gross abnormalities (except for dilatation) of MPD and noncircumferential microscopic involvement of MPD limited to few sections. RESULTS: We identified 46 min-mix-IPMNs, 163 IPMNs with extensive involvement of MPD (ex-mix-IPMN), 175 branch-duct (BD)-IPMNs, and 20 MD-IPMNs. The majority of min-mix-IPMNs were found incidentally and increased cyst size on surveillance was the leading operative indication. The median diameter of MPD was 2 mm in min-mix-IPMN versus 9 mm in ex-mix-IPMN (P < .0001), and cysts ≥10 mm were present in 62% of ex-mix-IPMNs versus 93% of min-mix-IPMNs (P < .0001). Most importantly, the vast majority of min-mix-IPMNs exhibited gastric-type epithelium, similar to BD-IPMNs, whereas intestinal-type epithelium was present in half of ex-mix-IPMNs, similar to MD-IPMNs. The prevalence of high-grade lesions was less in min-mix-IPMN than ex-mix-IPMN (P < .0001). These differences were reflected in better disease-specific outcomes of min-mix-IPMN compared with ex-mix-IPMN (P = .046). CONCLUSION: Min-mix-IPMN often presents with no MPD dilation and is an incidental finding by microscopic examination. min-mix-IPMN shares the pathologic features and less aggressive biology with BD-IPMN. We propose that min-mix-IPMN be categorized differently than ex-mix-IPMN.

21 Article Enhanced primary tumor delineation in pancreatic adenocarcinoma using ultrasmall super paramagnetic iron oxide nanoparticle-ferumoxytol: an initial experience with histopathologic correlation. 2014

Hedgire, Sandeep S / Mino-Kenudson, Mari / Elmi, Azadeh / Thayer, Sarah / Fernandez-del Castillo, Carlos / Harisinghani, Mukesh G. ·Department of Abdominal Imaging and Intervention, Massachusetts General Hospital, Boston, MA, USA. · Department of Pathology, Massachusetts General Hospital, Boston, MA, USA. · Department of Surgery, Massachusetts General Hospital, Boston, MA, USA. ·Int J Nanomedicine · Pubmed #24790431.

ABSTRACT: PURPOSE: To evaluate the role of ferumoxytol-enhanced magnetic resonance imaging (MRI) in delineating primary pancreatic tumors in patients undergoing preoperative neoadjuvant therapy. MATERIALS AND METHODS: Eight patients with pancreatic adenocarcinoma were enrolled in this study, and underwent MRI scans at baseline, immediate post, and at the 48 hour time point after ferumoxytol injection with quantitative T2* sequences. The patients were categorized into two groups; group A received preoperative neoadjuvant therapy and group B did not. The T2* of the primary pancreatic tumor and adjacent parenchyma was recorded at baseline and the 48 hour time point. After surgery, the primary tumors were assessed histopathologically for fibrosis and inflammation. RESULTS: The mean T2* of the primary tumor and adjacent parenchyma at 48 hours in group A were 22.11 ms and 16.34 ms, respectively; in group B, these values were 23.96 ms and 23.26 ms, respectively. The T2* difference between the tumor and adjacent parenchyma in group A was more pronounced compared to in group B. The tumor margins were subjectively more distinct in group A compared to group B. Histopathologic evaluation showed a rim of dense fibrosis with atrophic acini at the periphery of the lesion in group A. Conversely, intact tumor cells/glands were present at the periphery of the tumor in group B. CONCLUSION: Ferumoxytol-enhanced MRI scans in patients receiving preoperative neoadjuvant therapy may offer enhanced primary tumor delineation, contributing towards achieving disease-free margin at the time of surgery, and thus improving the prognosis of pancreatic carcinomas.

22 Article Branch duct intraductal papillary mucinous neoplasms: does cyst size change the tip of the scale? A critical analysis of the revised international consensus guidelines in a large single-institutional series. 2013

Sahora, Klaus / Mino-Kenudson, Mari / Brugge, William / Thayer, Sarah P / Ferrone, Cristina R / Sahani, Dushyant / Pitman, Martha B / Warshaw, Andrew L / Lillemoe, Keith D / Fernandez-del Castillo, Carlos F. ·Departments of *Surgery †Pathology ‡Gastroenterology and §Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA. ·Ann Surg · Pubmed #24022439.

ABSTRACT: OBJECTIVE: The aim of this study was to critically analyze the safety of the revised guidelines, with focus on cyst size and worrisome features in the management of BD-IPMN. BACKGROUND: The Sendai guidelines for management of branch duct (BD) intraductal papillary mucinous neoplasm (IPMN) espouse safety of observation of asymptomatic cysts smaller than 3 cm without nodules (Sendai negative). Revised international consensus guidelines published in 2012 suggest a still more conservative approach, even for lesions of 3 cm or larger. By contrast, 2 recent studies have challenged the safety of both guidelines, describing invasive carcinoma or carcinoma in situ in 67% of BD-IPMN smaller than 3 cm and in 25% of "Sendai-negative" BD-IPMN. METHODS AND RESULTS: Review of a prospective database identified 563 patients with BD-IPMN. A total of 240 patients underwent surgical resection (152 at the time of diagnosis and 88 after being initially followed); the remaining 323 have been managed by observation with median follow-up of 60 months. No patient developed unresectable BD-IPMN carcinoma during follow-up. Invasive cancer arising in BD-IPMN was found in 23 patients of the entire cohort (4%), and an additional 21 patients (3.7%) had or developed concurrent pancreatic ductal adenocarcinoma. According to the revised guidelines, 76% of resected BD-IPMN with carcinoma in situ and 95% of resected BD-IPMN with invasive cancer had high-risk stigmata or worrisome features. The risk of high-grade dysplasia in nonworrisome lesions smaller than 3 cm was 6.5%, but when the threshold was raised to greater than 3 cm, it was 8.8%, and 1 case of invasive carcinoma was found. CONCLUSIONS: Expectant management of BD-IPMN following the old guidelines is safe, whereas caution is advised for larger lesions, even in the absence of worrisome features.

23 Article Updated long-term outcomes and prognostic factors for patients with unresectable locally advanced pancreatic cancer treated with intraoperative radiotherapy at the Massachusetts General Hospital, 1978 to 2010. 2013

Cai, Sophie / Hong, Theodore S / Goldberg, Saveli I / Fernandez-del Castillo, Carlos / Thayer, Sarah P / Ferrone, Cristina R / Ryan, David P / Blaszkowsky, Lawrence S / Kwak, Eunice L / Willett, Christopher G / Lillemoe, Keith D / Warshaw, Andrew L / Wo, Jennifer Y. ·Harvard Medical School, Boston, Massachusetts. ·Cancer · Pubmed #24006012.

ABSTRACT: BACKGROUND: In the current study, the authors evaluated long-term outcomes, intraoperative radiotherapy (IORT)-related toxicity, and prognostic factors for overall survival (OS) among patients with unresectable locally advanced pancreatic cancer (LAPC) who received IORT as part of their treatment at the Massachusetts General Hospital (MGH). METHODS: Medical records were reviewed for 194 consecutive patients with unresectable LAPC who were treated with IORT at MGH between 1978 and 2010. OS was calculated using the Kaplan-Meier method. Prognostic factors were evaluated at the univariate level by the log-rank test and at the multivariate level by the Cox proportional hazards model. Rates of disease progression and treatment toxicity were calculated. RESULTS: The 1-year, 2-year, and 3-year survival rates were 49%, 16%, and 6%, respectively. Six patients (3%) survived for > 5 years. The median OS was 12.0 months. Among 183 patients with known post-IORT disease status, the 2-year local progression-free survival and distant metastasis-free survival rates were 41% and 28%, respectively. On multivariate analysis, an IORT applicator diameter ≤ 8 cm (hazards ratio [HR], 0.51; 95% confidence interval [95% CI], 0.30-0.84 [P = .009]), a Charlson age-comorbidity index ≤ 3 (HR, 0.47; 95% CI, 0.31-0.73 [P = .001]), and receipt of chemotherapy (HR, 0.46; 95% CI, 0.33-0.66 [P < .001]) predicted improved OS. The median OS for patients with all 3 positive prognostic factors was 21.2 months. CONCLUSIONS: Well-selected patients with LAPC with small tumors and low Charlson age-comorbidity indices can achieve good long-term survival outcomes with a treatment regimen that incorporates chemotherapy and IORT.

24 Article FOLFIRINOX in locally advanced pancreatic cancer: the Massachusetts General Hospital Cancer Center experience. 2013

Faris, Jason E / Blaszkowsky, Lawrence S / McDermott, Shaunagh / Guimaraes, Alexander R / Szymonifka, Jackie / Huynh, Mai Anh / Ferrone, Cristina R / Wargo, Jennifer A / Allen, Jill N / Dias, Lauren E / Kwak, Eunice L / Lillemoe, Keith D / Thayer, Sarah P / Murphy, Janet E / Zhu, Andrew X / Sahani, Dushyant V / Wo, Jennifer Y / Clark, Jeffrey W / Fernandez-del Castillo, Carlos / Ryan, David P / Hong, Theodore S. ·Department of Hematology/Oncology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. jfaris@partners.org ·Oncologist · Pubmed #23657686.

ABSTRACT: The objective of our retrospective institutional experience is to report the overall response rate, R0 resection rate, progression-free survival, and safety/toxicity of neoadjuvant FOLFIRINOX (5-fluorouracil [5-FU], oxaliplatin, irinotecan, and leucovorin) and chemoradiation in patients with locally advanced pancreatic cancer (LAPC). Patients with LAPC treated with FOLFIRINOX were identified via the Massachusetts General Hospital Cancer Center pharmacy database. Demographic information, clinical characteristics, and safety/tolerability data were compiled. Formal radiographic review was performed to determine overall response rates (ORRs). Twenty-two patients with LAPC began treatment with FOLFIRINOX between July 2010 and February 2012. The ORR was 27.3%, and the median progression-free survival was 11.7 months. Five of 22 patients were able to undergo R0 resections following neoadjuvant FOLFIRINOX and chemoradiation. Three of the five patients have experienced distant recurrence within 5 months. Thirty-two percent of patients required at least one emergency department visit or hospitalization while being treated with FOLFIRINOX. FOLFIRINOX possesses substantial activity in patients with LAPC. The use of FOLFIRINOX was associated with conversion to resectability in >20% of patients. However, the recurrences following R0 resection in three of five patients and the toxicities observed with the use of this regimen raise important questions about how to best treat patients with LAPC.

25 Article N0/N1, PNL, or LNR? The effect of lymph node number on accurate survival prediction in pancreatic ductal adenocarcinoma. 2013

Valsangkar, Nakul P / Bush, Devon M / Michaelson, James S / Ferrone, Cristina R / Wargo, Jennifer A / Lillemoe, Keith D / Fernández-del Castillo, Carlos / Warshaw, Andrew L / Thayer, Sarah P. ·Department of Surgery and Andrew L. Warshaw, M.D., Institute for Pancreatic Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. ·J Gastrointest Surg · Pubmed #23229885.

ABSTRACT: INTRODUCTION: We evaluated the prognostic accuracy of LN variables (N0/N1), numbers of positive lymph nodes (PLN), and lymph node ratio (LNR) in the context of the total number of examined lymph nodes (ELN). METHODS: Patients from SEER and a single institution (MGH) were reviewed and survival analyses performed in subgroups based on numbers of ELN to calculate excess risk of death (hazard ratio, HR). RESULTS: In SEER and MGH, higher numbers of ELN improved the overall survival for N0 patients. The prognostic significance (N0/N1) and PLN were too variable as the importance of a single PLN depended on the total number of LN dissected. LNR consistently correlated with survival once a certain number of lymph nodes were dissected (≥13 in SEER and ≥17 in the MGH dataset). CONCLUSIONS: Better survival for N0 patients with increasing ELN likely represents improved staging. PLN have some predictive value but the ELN strongly influence their impact on survival, suggesting the need for a ratio-based classification. LNR strongly correlates with outcome provided that a certain number of lymph nodes is evaluated, suggesting that the prognostic accuracy of any LN variable depends on the total number of ELN.

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