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Pancreatic Neoplasms: HELP
Articles by Michael G. Goggins
Based on 138 articles published since 2010
(Why 138 articles?)
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Between 2010 and 2020, M. Goggins wrote the following 138 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6
1 Guideline Evaluating Susceptibility to Pancreatic Cancer: ASCO Provisional Clinical Opinion. 2019

Stoffel, Elena M / McKernin, Shannon E / Brand, Randall / Canto, Marcia / Goggins, Michael / Moravek, Cassadie / Nagarajan, Arun / Petersen, Gloria M / Simeone, Diane M / Yurgelun, Matthew / Khorana, Alok A. ·1 University of Michigan, Ann Arbor, MI. · 2 American Society of Clinical Oncology, Alexandria, VA. · 3 University of Pittsburgh, Pittsburgh, PA. · 4 Johns Hopkins University, Baltimore, MD. · 5 Pancreatic Cancer Action Network, Los Angeles, CA. · 6 Taussig Cancer Institute and Case Comprehensive Cancer Center, Cleveland Clinic, Cleveland, OH. · 7 Mayo Clinic, Rochester, MN. · 8 New York University Langone Health, New York, NY. · 9 Dana-Farber Cancer Institute, Boston, MA. ·J Clin Oncol · Pubmed #30457921.

ABSTRACT: PURPOSE: An ASCO provisional clinical opinion (PCO) offers timely clinical direction to ASCO's membership and other health care providers. This PCO addresses identification and management of patients and family members with possible predisposition to pancreatic adenocarcinoma. METHODS: ASCO convened an Expert Panel and conducted a systematic review of the literature published from January 1998 to June 2018. Results of the databases searched were supplemented with hand searching of the bibliographies of systematic reviews and selected seminal articles and contributions from Expert Panel members' curated files. PROVISIONAL CLINICAL OPINION: All patients diagnosed with pancreatic adenocarcinoma should undergo assessment of risk for hereditary syndromes known to be associated with an increased risk for pancreatic adenocarcinoma. Assessment of risk should include a comprehensive review of family history of cancer. Individuals with a family history of pancreatic cancer affecting two first-degree relatives meet criteria for familial pancreatic cancer (FPC). Individuals (cancer affected or unaffected) with a family history of pancreatic cancer meeting criteria for FPC, those with three or more diagnoses of pancreatic cancer in same side of the family, and individuals meeting criteria for other genetic syndromes associated with increased risk for pancreatic cancer have an increased risk for pancreatic cancer and are candidates for genetic testing. Germline genetic testing for cancer susceptibility may be discussed with individuals diagnosed with pancreatic cancer, even if family history is unremarkable. Benefits and limitations of pancreatic cancer screening should be discussed with individuals whose family history meets criteria for FPC and/or genetic susceptibility to pancreatic cancer. Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines .

2 Guideline International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer. 2013

Canto, Marcia Irene / Harinck, Femme / Hruban, Ralph H / Offerhaus, George Johan / Poley, Jan-Werner / Kamel, Ihab / Nio, Yung / Schulick, Richard S / Bassi, Claudio / Kluijt, Irma / Levy, Michael J / Chak, Amitabh / Fockens, Paul / Goggins, Michael / Bruno, Marco / Anonymous4740741. ·Division of Gastroenterology, Johns Hopkins University, The Sol Goldman Pancreatic Cancer Research Center, 1830 E Monument Street, Baltimore, MD 21205, USA. mcanto@jhmi.edu ·Gut · Pubmed #23135763.

ABSTRACT: BACKGROUND: Screening individuals at increased risk for pancreatic cancer (PC) detects early, potentially curable, pancreatic neoplasia. OBJECTIVE: To develop consortium statements on screening, surveillance and management of high-risk individuals with an inherited predisposition to PC. METHODS: A 49-expert multidisciplinary international consortium met to discuss pancreatic screening and vote on statements. Consensus was considered reached if ≥ 75% agreed or disagreed. RESULTS: There was excellent agreement that, to be successful, a screening programme should detect and treat T1N0M0 margin-negative PC and high-grade dysplastic precursor lesions (pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasm). It was agreed that the following were candidates for screening: first-degree relatives (FDRs) of patients with PC from a familial PC kindred with at least two affected FDRs; patients with Peutz-Jeghers syndrome; and p16, BRCA2 and hereditary non-polyposis colorectal cancer (HNPCC) mutation carriers with ≥ 1 affected FDR. Consensus was not reached for the age to initiate screening or stop surveillance. It was agreed that initial screening should include endoscopic ultrasonography (EUS) and/or MRI/magnetic resonance cholangiopancreatography not CT or endoscopic retrograde cholangiopancreatography. There was no consensus on the need for EUS fine-needle aspiration to evaluate cysts. There was disagreement on optimal screening modalities and intervals for follow-up imaging. When surgery is recommended it should be performed at a high-volume centre. There was great disagreement as to which screening abnormalities were of sufficient concern to for surgery to be recommended. CONCLUSIONS: Screening is recommended for high-risk individuals, but more evidence is needed, particularly for how to manage patients with detected lesions. Screening and subsequent management should take place at high-volume centres with multidisciplinary teams, preferably within research protocols.

3 Editorial Intercepting Pancreatic Cancer: Our Dream Team's Resolve to Stop Pancreatic Cancer. 2018

Goggins, Michael G / Lippman, Scott M / Constantinou, Pamela E / Jacks, Tyler / Petersen, Gloria M / Syngal, Sapna / Maitra, Anirban. ·Division of Hematology/Oncology, Department of Medicine, Moores Center for Personalized Cancer Therapy, University of California, San Diego, La Jolla, CA. · Sheikh Ahmed Center for Pancreatic Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, TX. · Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN. ·Pancreas · Pubmed #30325853.

ABSTRACT: -- No abstract --

4 Review Genetics of Familial and Sporadic Pancreatic Cancer. 2019

Wood, Laura D / Yurgelun, Matthew B / Goggins, Michael G. ·Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Oncology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: ldwood@jhmi.edu. · Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts; Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. Electronic address: Matthew_Yurgelun@dfci.harvard.edu. · Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Oncology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Medicine, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: mgoggins@jhmi.edu. ·Gastroenterology · Pubmed #30660730.

ABSTRACT: In the previous decade, comprehensive genomic analyses have yielded important insights about the genetic alterations that underlie pancreatic tumorigenesis. Whole-exome and whole-genome sequencing of pancreatic ductal adenocarcinomas have confirmed the critical driver genes altered in the majority of pancreatic cancers, as well as identified numerous less frequently altered driver genes, and have delineated cancer subgroups with unique biological and clinical features. It is now appreciated that pancreatic susceptibility gene alterations are often identified in patients with pancreatic cancer without family histories suggestive of a familial cancer syndrome, prompting recent efforts to expand gene testing to all patients with pancreatic cancer. Studies of pancreatic cancer precursor lesions have begun to elucidate the evolutionary history of pancreatic tumorigenesis and to help us understand the utility of biomarkers for early detection and targets to develop new therapeutic strategies. In this review, we discuss the results of comprehensive genomic characterization of pancreatic ductal adenocarcinoma and its precursor lesions, and we highlight translational applications in early detection and therapy.

5 Review The Gut Microbiome in Pancreatic Disease. 2019

Akshintala, Venkata S / Talukdar, Rupjyoti / Singh, Vikesh K / Goggins, Michael. ·Division of Gastroenterology, Department of Medicine, Johns Hopkins Medical Institution, Baltimore, Maryland. · Department of Medical Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, India; Wellcome DBT Laboratories, Asian Healthcare Foundation, Hyderabad, India. · Division of Gastroenterology, Department of Medicine, Johns Hopkins Medical Institution, Baltimore, Maryland; Department of Pathology, Johns Hopkins Medical Institution, Baltimore, Maryland; Department of Oncology, Johns Hopkins Medical Institution, Baltimore, Maryland; The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institution, Baltimore, Maryland. Electronic address: mgoggins@jhmi.edu. ·Clin Gastroenterol Hepatol · Pubmed #30144522.

ABSTRACT: The gut microbiome increasingly is recognized for its role in human health and disease. Initial evidence has indicated that gut microbial dysbiosis is associated with several pancreatic diseases. Although it is not known if these associations are causative, gut dysbiosis is hypothesized to mediate chronic proinflammatory changes in the pancreas. Further mechanistic and epidemiologic studies of the microbiome are needed. Ultimately, targeted modulation of the microbiota could have therapeutic value.

6 Review Diagnosis and Detection of Pancreatic Cancer. 2017

Chu, Linda C / Goggins, Michael G / Fishman, Elliot K. · ·Cancer J · Pubmed #29189329.

ABSTRACT: Computed tomography is the first-line imaging modality for suspected pancreatic cancer. Magnetic resonance cholangiopancreatography is a second-line modality for suspected pancreatic cancer and is usually reserved for equivocal cases. Both computed tomography and MR are highly sensitive in the detection of pancreatic cancer, with up to 96% and 93.5% sensitivity, respectively. Computed tomography is superior to MR in the assessment of tumor resectability, with accuracy rates of up to 86.8% and 78.9%, respectively. Close attention to secondary signs of pancreatic cancer, such as pancreatic duct dilatation, abrupt pancreatic duct caliber change, and parenchymal atrophy, are critical in the diagnosis of pancreatic cancer. Emerging techniques such as radiomics and molecular imaging have the potential of identifying malignant precursors and lead to earlier disease diagnosis. The results of these promising techniques need to be validated in larger clinical studies.

7 Review Role of hyaluronan in pancreatic cancer biology and therapy: Once again in the spotlight. 2016

Sato, Norihiro / Kohi, Shiro / Hirata, Keiji / Goggins, Michael. ·Department of Surgery 1, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan. · Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA. ·Cancer Sci · Pubmed #26918382.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) remains the most deadly disease worldwide, with the lowest survival rate among all cancer types. Recent evidence suggests that hyaluronan (HA), a major component of ECM, provides a favorable microenvironment for cancer progression. Pancreatic ductal adenocarcinoma is typically characterized by a dense desmoplastic stroma containing a large amount of HA. Accumulation of HA promotes tumor growth in mice and correlates with poor prognosis in patients with PDAC. Because HA is involved in various malignant behaviors of cancer (such as increased cell proliferation, migration, invasion, angiogenesis, and chemoresistance), inhibiting HA synthesis/signaling or depleting HA in tumor stroma could represent a promising therapeutic strategy against PDAC. In this review article, we summarize our current understanding of the role of HA in the progression of PDAC and discuss possible therapeutic approaches targeting HA.

8 Review Pathological and molecular evaluation of pancreatic neoplasms. 2015

Rishi, Arvind / Goggins, Michael / Wood, Laura D / Hruban, Ralph H. ·Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD. · Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD. · Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD. Electronic address: rhruban@jhmi.edu. ·Semin Oncol · Pubmed #25726050.

ABSTRACT: Pancreatic neoplasms are morphologically and genetically heterogeneous and include a wide variety of tumors ranging from benign to malignant with an extremely poor clinical outcome. Our understanding of these pancreatic neoplasms has improved significantly with recent advances in cancer sequencing. Awareness of molecular pathogenesis brings new opportunities for early detection, improved prognostication, and personalized gene-specific therapies. Here we review the pathological classification of pancreatic neoplasms from the molecular and genetic perspectives.

9 Review The early detection of pancreatic cancer: what will it take to diagnose and treat curable pancreatic neoplasia? 2014

Lennon, Anne Marie / Wolfgang, Christopher L / Canto, Marcia Irene / Klein, Alison P / Herman, Joseph M / Goggins, Michael / Fishman, Elliot K / Kamel, Ihab / Weiss, Matthew J / Diaz, Luis A / Papadopoulos, Nickolas / Kinzler, Kenneth W / Vogelstein, Bert / Hruban, Ralph H. ·Authors' Affiliations: Departments of Medicine; Surgery; · Surgery; Pathology; Oncology; · Authors' Affiliations: Departments of Medicine; · Pathology; Oncology; Department of Epidemiology, the Bloomberg School of Public Health, Baltimore, Maryland. · Oncology; Radiation Oncology; and. · Authors' Affiliations: Departments of Medicine; Pathology; Oncology; · Radiology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine; and. · Surgery; · Oncology; · Pathology; Oncology; · Pathology; Oncology; rhruban@jhmi.edu. ·Cancer Res · Pubmed #24924775.

ABSTRACT: Pancreatic cancer is the deadliest of all solid malignancies. Early detection offers the best hope for a cure, but characteristics of this disease, such as the lack of early clinical symptoms, make the early detection difficult. Recent genetic mapping of the molecular evolution of pancreatic cancer suggests that a large window of opportunity exists for the early detection of pancreatic neoplasia, and developments in cancer genetics offer new, potentially highly specific approaches for screening of curable pancreatic neoplasia. We review the challenges of screening for early pancreatic neoplasia, as well as opportunities presented by incorporating molecular genetics into these efforts.

10 Review A systematic review of solid-pseudopapillary neoplasms: are these rare lesions? 2014

Law, Joanna K / Ahmed, Aadil / Singh, Vikesh K / Akshintala, Venkata S / Olson, Matthew T / Raman, Siva P / Ali, Syed Z / Fishman, Elliot K / Kamel, Ihab / Canto, Marcia I / Dal Molin, Marco / Moran, Robert A / Khashab, Mouen A / Ahuja, Nita / Goggins, Michael / Hruban, Ralph H / Wolfgang, Christopher L / Lennon, Anne Marie. ·From the *Division of Gastroenterology, †Department of Pathology, ‡Department of Radiology, Johns Hopkins University School of Medicine, §Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, and ∥Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD. ·Pancreas · Pubmed #24622060.

ABSTRACT: OBJECTIVE: The aim of the study was to determine if there had been any change in the number of solid-pseudopapillary neoplasm (SPN) cases detected and their evaluation or management over time. METHODS: A systematic review of SPN was performed of all articles published in English in PubMed and Scopus. RESULTS: A total of 2744 patients with SPN were identified in 484 studies published between 1961 and 2012; 87.8% of the cases were reported between 2000 and 2012. A total of 2408 (87.8%) were females, and the mean age was 28.5 (SD, 13.7) years. The most common symptom was abdominal pain in 63.6% of the cases and incidentally detected in 38.1% of the cases. There were 2285 patients who underwent pancreatic resection. The mean tumor size was 8.6 (SD, 4.3) cm. Follow-up was reported for 1952 (90.5%) patients, with a mean follow-up of 36.1 (SD, 32.8) months. Disease-free survival was documented in 1866 (95.6%) patients with recurrence in 86 (4.4%) patients; the median time to recurrence was 50.5 months. CONCLUSIONS: The number of SPNs reported in the literature has seen a 7-fold increase in the number of cases reported since 2000 compared with before. Solid-pseudopapillary neoplasms continue to be primarily found in young women and present with nonspecific symptoms. Surgery remains the mainstay of treatment with an excellent long-term prognosis.

11 Review Molecular signatures of pancreatic cancer. 2011

Hong, Seung-Mo / Park, Jason Y / Hruban, Ralph H / Goggins, Michael. ·Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA. ·Arch Pathol Lab Med · Pubmed #21631264.

ABSTRACT: CONTEXT: The introduction of genome- and epigenome-wide screening techniques has dramatically improved our understanding of the molecular mechanisms underlying the development of pancreatic cancer. There are now 3 recognized histologic precursors of pancreatic cancer: pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasm, and mucinous cystic neoplasm. Each of these precursor lesions is associated with specific molecular alterations. OBJECTIVE: To understand the molecular characteristics of pancreatic ductal adenocarcinoma and its precursor lesions. DATA SOURCES: PubMed (US National Library of Medicine). CONCLUSIONS: In this review, we briefly summarize recent research findings on the genetics and epigenetics of pancreatic cancer. In addition, we characterize these molecular alterations in the context of the histologic subtypes of pancreatic cancer.

12 Review Pancreatic cancer. 2011

Vincent, Audrey / Herman, Joseph / Schulick, Rich / Hruban, Ralph H / Goggins, Michael. ·Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Johns Hopkins University, Baltimore, MD 21231, USA. ·Lancet · Pubmed #21620466.

ABSTRACT: Substantial progress has been made in our understanding of the biology of pancreatic cancer, and advances in patients' management have also taken place. Evidence is beginning to show that screening first-degree relatives of individuals with several family members affected by pancreatic cancer can identify non-invasive precursors of this malignant disease. The incidence of and number of deaths caused by pancreatic tumours have been gradually rising, even as incidence and mortality of other common cancers have been declining. Despite developments in detection and management of pancreatic cancer, only about 4% of patients will live 5 years after diagnosis. Survival is better for those with malignant disease localised to the pancreas, because surgical resection at present offers the only chance of cure. Unfortunately, 80-85% of patients present with advanced unresectable disease. Furthermore, pancreatic cancer responds poorly to most chemotherapeutic agents. Hence, we need to understand the biological mechanisms that contribute to development and progression of pancreatic tumours. In this Seminar we will discuss the most common and deadly form of pancreatic cancer, pancreatic ductal adenocarcinoma.

13 Review Update on familial pancreatic cancer. 2010

Hruban, Ralph H / Canto, Marcia I / Goggins, Michael / Schulick, Richard / Klein, Alison P. ·Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, 401 North Broadway, Weinberg 2242, Baltimore, MD 21231, USA. rhruban@jhmi.edu ·Adv Surg · Pubmed #20919528.

ABSTRACT: -- No abstract --

14 Clinical Trial Mutations in the pancreatic secretory enzymes 2018

Tamura, Koji / Yu, Jun / Hata, Tatsuo / Suenaga, Masaya / Shindo, Koji / Abe, Toshiya / MacGregor-Das, Anne / Borges, Michael / Wolfgang, Christopher L / Weiss, Matthew J / He, Jin / Canto, Marcia Irene / Petersen, Gloria M / Gallinger, Steven / Syngal, Sapna / Brand, Randall E / Rustgi, Anil / Olson, Sara H / Stoffel, Elena / Cote, Michele L / Zogopoulos, George / Potash, James B / Goes, Fernando S / McCombie, Richard W / Zandi, Peter P / Pirooznia, Mehdi / Kramer, Melissa / Parla, Jennifer / Eshleman, James R / Roberts, Nicholas J / Hruban, Ralph H / Klein, Alison Patricia / Goggins, Michael. ·Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205. · Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD 21205. · Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205. · The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21205. · Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205. · Health Sciences Research, Mayo Clinic, Rochester, MN 55905. · Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada M5G 1X5. · Population Sciences Division, Dana-Farber Cancer Institute, Boston, MA 02215. · Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213. · Division of Gastroenterology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104. · Department of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104. · Pancreatic Cancer Translational Center of Excellence, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104. · Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104. · Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10017. · Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109. · Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201. · The Research Institute of the McGill University Health Centre, McGill University, Montreal, QC, Canada H3H 2R9. · The Goodman Cancer Research Centre, McGill University, Montreal, QC, Canada H3A 1A3. · Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, MD 21287. · Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724. · InGenious Targeting Laboratory, Ronkonkoma, NY 11779. · Department of Epidemiology, Bloomberg School of Public Health, The Johns Hopkins University School of Medicine, Baltimore, MD 21205. · Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; mgoggins@jhmi.edu. ·Proc Natl Acad Sci U S A · Pubmed #29669919.

ABSTRACT: To evaluate whether germline variants in genes encoding pancreatic secretory enzymes contribute to pancreatic cancer susceptibility, we sequenced the coding regions of

15 Clinical Trial Role of a multidisciplinary clinic in the management of patients with pancreatic cysts: a single-center cohort study. 2014

Lennon, Anne Marie / Manos, Lindsey L / Hruban, Ralph H / Ali, Syed Z / Fishman, Elliot K / Kamel, Ihab R / Raman, Siva P / Zaheer, Atif / Hutfless, Susan / Salamone, Ashley / Kiswani, Vandhana / Ahuja, Nita / Makary, Martin A / Weiss, Matthew J / Hirose, Kenzo / Goggins, Michael / Wolfgang, Christopher L. ·Division of Gastroenterology and Hepatology, The Johns Hopkins Medical Institutions, Baltimore, MD. · Department of Surgery, The Johns Hopkins Medical Institutions, Baltimore, MD. · Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Medical Institutions, Baltimore, MD. · Department of Radiology, The Johns Hopkins Medical Institutions, Baltimore, MD. · Department of Oncology, The Johns Hopkins Medical Institutions, Baltimore, MD. ·Ann Surg Oncol · Pubmed #24806116.

ABSTRACT: BACKGROUND: Incidental pancreatic cysts are common, a small number of which are premalignant or malignant. Multidisciplinary care has been shown to alter management and improve outcomes in many types of cancers, but its role has not been examined in patients with pancreatic cysts. We assessed the effect of a multidisciplinary pancreatic cyst clinic (MPCC) on the diagnosis and management of patients with pancreatic cysts. METHODS: The referring institution and MPCC diagnosis and management plan were recorded. Patient were placed into one of five categories-no, low, intermediate, or high risk of malignancy within the cyst, and malignant cyst-on the basis of their diagnosis. Patients were assigned one of four management options: surveillance, surgical resection, further evaluation, or discharge with no further follow-up required. The MPCC was deemed to have altered patient care if the patient was assigned a different risk or management category after the MPCC review. RESULTS: Referring institution records were available for 262 patients (198 women; mean age 62.7 years), with data on risk category available in 138 patients and management category in 225. The most common diagnosis was branch duct intraductal papillary mucinous neoplasm. MPCC review altered the risk category in 11 (8.0%) of 138 patients. The management category was altered in 68 (30.2%) of 225 patients. Management was increased in 52 patients, including 22 patients who were recommended surgical resection. Management was decreased in 16 patients, including 10 who had their recommendation changed from surgery to surveillance. CONCLUSIONS: MPCC is helpful and alters the management over 30% of patients.

16 Article Management of patients with increased risk for familial pancreatic cancer: updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium. 2020

Goggins, Michael / Overbeek, Kasper Alexander / Brand, Randall / Syngal, Sapna / Del Chiaro, Marco / Bartsch, Detlef K / Bassi, Claudio / Carrato, Alfredo / Farrell, James / Fishman, Elliot K / Fockens, Paul / Gress, Thomas M / van Hooft, Jeanin E / Hruban, R H / Kastrinos, Fay / Klein, Allison / Lennon, Anne Marie / Lucas, Aimee / Park, Walter / Rustgi, Anil / Simeone, Diane / Stoffel, Elena / Vasen, Hans F A / Cahen, Djuna L / Canto, Marcia Irene / Bruno, Marco / Anonymous1881192. ·Pathology, Medicine Oncology, Johns Hopkins University, Baltimore, Maryland, USA mgoggins@jhmi.edu. · Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands. · Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA. · GI Cancer Genetics and Prevention Program, Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, USA. · Department of Surgery, Division of Surgical Oncology, Denver, Colorado, USA. · Division of Visceral, Thoracic and Vascular Surgery, University of Marburg, Marburg, Germany. · Department of Surgey, University of Verona, Verona, Italy. · Medical Oncology, Hospital Ramón y Cajal, Madrid, Spain. · Medicine, Yale University School of Medicine, New Haven, Connecticut, USA. · The Russell H Morgan Department of Radiology and Radiological Science, Baltimore, Maryland, USA. · Department of Gastroenterology & Hepatology, Amsterdam Gastroenterology & Metabolism, Amsterdam, The Netherlands. · Gastroenterology, Endocrinology, Metabolism and Infectiology, University of Marburg, Marburg, Germany. · Gastroenterology and Hepatology, Amsterdam University Medical Centres, Amsterdam, The Netherlands. · Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA. · Division of Digestive and Liver Diseases, Columbia University Medical Center, New York City, New York, USA. · Division of Digestive and Liver Diseases, Columbia University, New York City, New York, USA. · Oncology, Johns Hopkins University, Baltimore, Maryland, USA. · Medicine, Johns Hopkins University, Baltimore, Maryland, USA. · Gastroenterology, Icahn School of Medicine at Mount Sinai, New York City, New York, USA. · New York University Medical Center, New York City, New York, USA. · University of Michigan, Ann Arbor, Michigan, USA. · Gastroenterology and Hepatology, Leiden University, Leiden, The Netherlands. ·Gut · Pubmed #31672839.

ABSTRACT: BACKGROUND AND AIM: The International Cancer of the Pancreas Screening Consortium met in 2018 to update its consensus recommendations for the management of individuals with increased risk of pancreatic cancer based on family history or germline mutation status (high-risk individuals). METHODS: A modified Delphi approach was employed to reach consensus among a multidisciplinary group of experts who voted on consensus statements. Consensus was considered reached if ≥75% agreed or disagreed. RESULTS: Consensus was reached on 55 statements. The main goals of surveillance (to identify high-grade dysplastic precursor lesions and T1N0M0 pancreatic cancer) remained unchanged. Experts agreed that for those with familial risk, surveillance should start no earlier than age 50 or 10 years earlier than the youngest relative with pancreatic cancer, but were split on whether to start at age 50 or 55. Germline CONCLUSIONS: Pancreatic surveillance is recommended for selected high-risk individuals to detect early pancreatic cancer and its high-grade precursors, but should be performed in a research setting by multidisciplinary teams in centres with appropriate expertise. Until more evidence supporting these recommendations is available, the benefits, risks and costs of surveillance of pancreatic surveillance need additional evaluation.

17 Article Surgical Outcomes After Pancreatic Resection of Screening-Detected Lesions in Individuals at High Risk for Developing Pancreatic Cancer. 2020

Canto, Marcia Irene / Kerdsirichairat, Tossapol / Yeo, Charles J / Hruban, Ralph H / Shin, Eun Ji / Almario, Jose Alejandro / Blackford, Amanda / Ford, Madeline / Klein, Alison P / Javed, Ammar A / Lennon, Anne Marie / Zaheer, Atif / Kamel, Ihab R / Fishman, Elliot K / Burkhart, Richard / He, Jin / Makary, Martin / Weiss, Matthew J / Schulick, Richard D / Goggins, Michael G / Wolfgang, Christopher L. ·Division of Gastroenterology and Hepatology, Department of Medicine, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Blalock 407, Baltimore, MD, 21287, USA. mcanto1@jhmi.edu. · Division of Gastroenterology and Hepatology, Department of Medicine, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Blalock 407, Baltimore, MD, 21287, USA. · Department of Surgery, Thomas Jefferson University, Philadelphia, PA, USA. · Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA. · Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA. · Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA. · Department of Radiology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA. · Department of Surgery, University of Colorado School of Medicine, Denver, CO, USA. ·J Gastrointest Surg · Pubmed #31197699.

ABSTRACT: BACKGROUND: Screening high-risk individuals (HRI) can detect potentially curable pancreatic ductal adenocarcinoma (PDAC) and its precursors. We describe the outcomes of high-risk individuals (HRI) after pancreatic resection of screen-detected neoplasms. METHODS: Asymptomatic HRI enrolled in the prospective Cancer of the Pancreas Screening (CAPS) studies from 1998 to 2014 based on family history or germline mutations undergoing surveillance for at least 6 months were included. Pathologic diagnoses, hospital length of stay, incidence of diabetes mellitus, operative morbidity, need for repeat operation, and disease-specific mortality were determined. RESULTS: Among 354 HRI, 48 (13.6%) had 57 operations (distal pancreatectomy (31), Whipple (20), and total pancreatectomy (6)) for suspected pancreatic neoplasms presenting as a solid mass (22), cystic lesion(s) (25), or duct stricture (1). The median length of stay was 7 days (IQR 5-11). Nine of the 42 HRI underwent completion pancreatectomy for a new lesion after a median of 3.8 years (IQR 2.5-7.6). Postoperative complications developed in 17 HRI (35%); there were no perioperative deaths. New-onset diabetes mellitus after partial resection developed in 20% of HRI. Fourteen PDACs were diagnosed, 11 were screen-detected, 10 were resectable, and 9 had an R0 resection. Metachronous PDAC developed in remnant pancreata of 2 HRI. PDAC-related mortality was 4/10 (40%), with 90% 1-year survival and 60% 5-year survival, respectively. CONCLUSIONS: Screening HRI can detect PDAC with a high resectability rate. Surgical treatment is associated with a relatively short length of stay and low readmission rate, acceptable morbidity, zero 90-day mortality, and significant long-term survival. CLINICAL TRIAL REGISTRATION NUMBER: NCT2000089.

18 Article Lactate-mediated epigenetic reprogramming regulates formation of human pancreatic cancer-associated fibroblasts. 2019

Bhagat, Tushar D / Von Ahrens, Dagny / Dawlaty, Meelad / Zou, Yiyu / Baddour, Joelle / Achreja, Abhinav / Zhao, Hongyun / Yang, Lifeng / Patel, Brijesh / Kwak, Changsoo / Choudhary, Gaurav S / Gordon-Mitchell, Shanisha / Aluri, Srinivas / Bhattacharyya, Sanchari / Sahu, Srabani / Bhagat, Prafulla / Yu, Yiting / Bartenstein, Matthias / Giricz, Orsi / Suzuki, Masako / Sohal, Davendra / Gupta, Sonal / Guerrero, Paola A / Batra, Surinder / Goggins, Michael / Steidl, Ulrich / Greally, John / Agarwal, Beamon / Pradhan, Kith / Banerjee, Debabrata / Nagrath, Deepak / Maitra, Anirban / Verma, Amit. ·Albert Einstein College of Medicine, Montefiore Medical Center, New York, United States. · Department of Biomedical Engineering, University of Michigan, Ann Arbor, United States. · Rutgers University, New Brunswick, United States. · Department of Pathology, Sheikh Ahmed Pancreatic Cancer Research Center, UT MD Anderson Cancer Center, Houston, United States. · Department of Translational Molecular Pathology, Sheikh Ahmed Pancreatic Cancer Research Center, UT MD Anderson Cancer Center, Houston, United States. · Department of Medicine, Cleveland Clinic, Cleveland, United States. · University of Nebraska Medical Center, Omaha, United States. · Johns Hopkins, Baltimore, United States. · GenomeRxUs LLC, Secane, United States. · Biointerfaces Institute, University of Michigan, Ann Arbor, United States. ·Elife · Pubmed #31663852.

ABSTRACT: Even though pancreatic ductal adenocarcinoma (PDAC) is associated with fibrotic stroma, the molecular pathways regulating the formation of cancer associated fibroblasts (CAFs) are not well elucidated. An epigenomic analysis of patient-derived and de-novo generated CAFs demonstrated widespread loss of cytosine methylation that was associated with overexpression of various inflammatory transcripts including

19 Article Hyaluronan activated-metabolism phenotype (HAMP) in pancreatic ductal adenocarcinoma. 2019

Kudo, Yuzan / Kohi, Shiro / Hirata, Keiji / Goggins, Michael / Sato, Norihiro. ·Department of Surgery 1, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan. · Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. ·Oncotarget · Pubmed #31608136.

ABSTRACT:

20 Article Follow-up of Incidentally Detected Pancreatic Cystic Neoplasms: Do Baseline MRI and CT Features Predict Cyst Growth? 2019

Pandey, Pallavi / Pandey, Ankur / Luo, Yan / Aliyari Ghasabeh, Mounes / Khoshpouri, Pegah / Ameli, Sanaz / O'Broin-Lennon, Anne Marie / Canto, Marcia / Hruban, Ralph H / Goggins, Michael S / Wolfgang, Christopher / Kamel, Ihab R. ·From the Russell H. Morgan Department of Radiology and Radiological Sciences (P.P., A.P., Y.L., M.A.G., P.K., S.Z., I.R.K.) and the Departments of Medicine, Division of Gastroenterology and Hepatology (A.M.O.L., M.C., M.S.G.), Pathology (R.H.H., M.S.G.), and Surgery, Division of Surgical Oncology (C.W.), Johns Hopkins University School of Medicine, 600 N Wolfe St, Room 143, Baltimore, MD 21287. ·Radiology · Pubmed #31310174.

ABSTRACT: Background Incidental detection of pancreatic cystic neoplasm (PCN) has increased. Since a small percentage of PCNs possess malignant potential, management is challenging. The recently revised American College of Radiology (ACR) recommendations define PCN measurement and growth for different categories based on baseline cyst size. However, no data are available regarding PCN growth rate under the ACR-defined size categories. Purpose To assess growth of incidentally detected PCNs on long-term imaging follow-up using revised ACR recommendations and to evaluate the association between baseline imaging features and growth. Materials and Methods This retrospective study included PCNs with baseline imaging performed between January 2002 and May 2017, with two or more cross-sectional imaging studies performed at least 12 months apart. PCN assessment was based on ACR 2017 recommendations. Cyst features, including location, septations, and mural nodules and multiplicity, were noted. Time to cyst progression (growth by ACR criteria) was examined by using baseline PCN size, among other factors. Results A total of 646 cysts in 390 patients were followed up for a median of 50 months (range, 12-186 months). A total of 184 (28.5%) cysts increased in size, 52 (8.1%) decreased in size, and 410 (63.4%) remained stable. For groups in which baseline PCN size was smaller than 5 mm, 5-14 mm, 15-25 mm, and larger than 25 mm, growth was noted in seven (13.2%), 106 (28.9%), 49 (32.2%), and 22 (29.7%) cysts, respectively. ACR baseline size categories (subhazard ratio: 2.8 [5-14-mm PCN group], 3.4 [15-25-mm PCN group], and 2.7 [>25 mm group], as compared with the <5 mm PCN group;

21 Article The glycan CA19-9 promotes pancreatitis and pancreatic cancer in mice. 2019

Engle, Dannielle D / Tiriac, Hervé / Rivera, Keith D / Pommier, Arnaud / Whalen, Sean / Oni, Tobiloba E / Alagesan, Brinda / Lee, Eun Jung / Yao, Melissa A / Lucito, Matthew S / Spielman, Benjamin / Da Silva, Brandon / Schoepfer, Christina / Wright, Kevin / Creighton, Brianna / Afinowicz, Lauren / Yu, Kenneth H / Grützmann, Robert / Aust, Daniela / Gimotty, Phyllis A / Pollard, Katherine S / Hruban, Ralph H / Goggins, Michael G / Pilarsky, Christian / Park, Youngkyu / Pappin, Darryl J / Hollingsworth, Michael A / Tuveson, David A. ·Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA. · Lustgarten Foundation Pancreatic Cancer Research Laboratory, Cold Spring Harbor, NY 11724, USA. · Gladstone Institutes, San Francisco, CA 94158, USA. · David M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. · Joan and Sanford I. Weill Medical College, Cornell University, New York, NY 10065, USA. · Department of Surgery, Universitätsklinikum Erlangen, 91054 Erlangen, Germany. · Institute for Pathology, Universitätsklinikum Dresden, 01307 Dresden, Germany. · Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, PA 19104, USA. · Department of Epidemiology and Biostatistics, Institute for Human Genetics, Quantitative Biology Institute, Institute for Computational Health Sciences, and Chan Zuckerberg Biohub, University of California, San Francisco, San Francisco, CA 94158, USA. · Sidney Kimmel Cancer Center, The Sol Goldman Pancreatic Cancer Research Center, and Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, MD 21231, USA. · Departments of Medicine and Oncology, School of Medicine, Johns Hopkins University, Baltimore, MD 21231, USA. · Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USA. · Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA. dtuveson@cshl.edu. ·Science · Pubmed #31221853.

ABSTRACT: Glycosylation alterations are indicative of tissue inflammation and neoplasia, but whether these alterations contribute to disease pathogenesis is largely unknown. To study the role of glycan changes in pancreatic disease, we inducibly expressed human fucosyltransferase 3 and β1,3-galactosyltransferase 5 in mice, reconstituting the glycan sialyl-Lewis

22 Article Deleterious Germline Mutations Are a Risk Factor for Neoplastic Progression Among High-Risk Individuals Undergoing Pancreatic Surveillance. 2019

Abe, Toshiya / Blackford, Amanda L / Tamura, Koji / Ford, Madeline / McCormick, Patrick / Chuidian, Miguel / Almario, Jose Alejandro / Borges, Michael / Lennon, Anne Marie / Shin, Eun Ji / Klein, Alison P / Hruban, Ralph H / Canto, Marcia I / Goggins, Michael. ·1 Johns Hopkins Medical Institutions, Baltimore, MD. ·J Clin Oncol · Pubmed #30883245.

ABSTRACT: PURPOSE: To compare the risk of neoplastic progression by germline mutation status versus family history without a known germline mutation (familial risk) among individuals with an increased risk for pancreatic cancer who are undergoing surveillance. METHODS: Of 464 high-risk individuals in the Cancer of the Pancreas Screening program at Johns Hopkins Hospital who were undergoing pancreatic surveillance, 119 had a known deleterious germline mutation in a pancreatic cancer susceptibility gene; 345 met family history criteria for pancreatic surveillance but were not known to harbor a germline mutation. We used next-generation sequencing to identify previously unrecognized germline mutations among these 345 individuals. We compared the development of pancreatic cancer, high-grade dysplasia, or clinically worrisome features, adjusting for competing mortality, among all germline mutation carriers with the risk of progression in a cohort without a known germline mutation. RESULTS: Fifteen (4.3%) of 345 individuals classified as having familial risk had a previously unrecognized pancreatic cancer susceptibility gene mutation (nine that involved CONCLUSION: The cumulative incidence of pancreatic cancer is significantly higher among individuals with an identifiable deleterious germline mutation in a pancreatic cancer susceptibility gene than it is among individuals with a strong family history but no identified mutation. Gene testing of individuals who meet criteria for pancreatic surveillance on the basis of their family history may better define those most at risk for neoplastic progression.

23 Article Pancreatic Juice Exosomal MicroRNAs as Biomarkers for Detection of Pancreatic Ductal Adenocarcinoma. 2019

Nakamura, So / Sadakari, Yoshihiko / Ohtsuka, Takao / Okayama, Takafumi / Nakashima, Yohei / Gotoh, Yoshitaka / Saeki, Kiyoshi / Mori, Yasuhisa / Nakata, Kohei / Miyasaka, Yoshihiro / Onishi, Hideya / Oda, Yoshinao / Goggins, Michael / Nakamura, Masafumi. ·Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Departments of Pathology, Medicine, and Oncology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Medical Institutions, Baltimore, MD, USA. · Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. mnaka@surg1.med.kyushu-u.ac.jp. ·Ann Surg Oncol · Pubmed #30820789.

ABSTRACT: BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a lethal neoplasm because of difficulties in early detection. Several studies have recently suggested that exosomes may have potential as novel biomarkers. This study aimed to isolate exosomes from pancreatic juice and to investigate whether exosomal microRNAs (ex-miRs) could be used as biomarkers for PDAC. METHODS: Pancreatic juice was collected from patients with PDAC and chronic pancreatitis (CP) by endoscopic retrograde pancreatography. Exosomes were extracted by ultracentrifugation. The presence of exosomes was confirmed by electron microscopy and Western blotting using anti-CD63, -CD81, and -TSG101 antibodies. Relative levels of ex-miR-21 and ex-miR-155 were quantified and compared between PDAC and CP patients. RESULTS: A total of 35 pancreatic juice samples (27 PDAC and 8 CP) were collected. Relative levels of both ex-miR-21 and ex-miR-155 were significantly higher in PDAC patients compared with CP patients (p < 0.001 and p = 0.008, respectively). By contrast, no significant difference was apparent in relative levels of miR-21 and miR-155 in whole pancreatic juice from PDAC patients compared with CP patients (p = 0.08 and p = 0.61, respectively). Ex-miR-21 and ex-miR-155 levels discriminated PDAC patients from CP patients with area under the curve values of 0.90 and 0.89, respectively. The accuracies of ex-miR-21 levels, ex-miR-155 levels, and pancreatic juice cytology were 83%, 89%, and 74%, respectively. When combining the results of ex-miR profiling with pancreatic juice cytology, the accuracy was improved to 91%. CONCLUSIONS: We successfully extracted exosomes from pancreatic juice. Ex-miRs, including ex-miR-21 and ex-miR-155, in pancreatic juice may be developed as biomarkers for PDAC.

24 Article Direct Interactions With Cancer-Associated Fibroblasts Lead to Enhanced Pancreatic Cancer Stem Cell Function. 2019

Begum, Asma / McMillan, Ross H / Chang, Yu-Tai / Penchev, Vesselin R / Rajeshkumar, N V / Maitra, Anirban / Goggins, Michael G / Eshelman, James R / Wolfgang, Christopher L / Rasheed, Zeshaan A / Matsui, William. ·Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX. · Departments of Pathology and. · Surgery, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD. ·Pancreas · Pubmed #30747824.

ABSTRACT: OBJECTIVE: Cancer-associated fibroblasts (CAFs) play an important role in the progression of pancreatic ductal adenocarcinoma (PDAC) by promoting tumor cell migration and drug resistance. We determined the impact of CAFs on PDAC cancer stem cells (CSCs). METHODS: Fibroblast cell lines from patients' tumors were cocultured with PDAC cells and examined for clonogenic growth and self-renewal using colony-forming assays and migration in vitro. Changes in the frequency of CSCs was determined by flow cytometry. The effect of integrin-focal adhesion kinase (FAK) signaling on CAF-mediated clonogenic growth was evaluated using short hairpin RNAs against β1 integrin and FAK as well as a small-molecule FAK inhibitor. RESULTS: Cancer-associated fibroblasts enhanced PDAC clonogenic growth, self-renewal, and migration that was associated with an increase in the frequency of CSCs. These fibroblast cells were activated by PDAC cells and increased collagen synthesis resulting in FAK activation in PDAC cells. Knockdown of β1-integrin and FAK or the inhibition of FAK kinase activity in PDAC cells abrogated the impact of CAFs on clonogenic growth. CONCLUSION: Therefore, CAFs enhance PDAC clonogenic growth, self-renewal, and the frequency of CSCs through type I collagen production that enhances integrin-FAK signaling in PDAC cells.

25 Article Prevalence of Germline Mutations Associated With Cancer Risk in Patients With Intraductal Papillary Mucinous Neoplasms. 2019

Skaro, Michael / Nanda, Neha / Gauthier, Christian / Felsenstein, Matthäus / Jiang, Zhengdong / Qiu, Miaozhen / Shindo, Koji / Yu, Jun / Hutchings, Danielle / Javed, Ammar A / Beckman, Ross / He, Jin / Wolfgang, Christopher L / Thompson, Elizabeth / Hruban, Ralph H / Klein, Alison P / Goggins, Michael / Wood, Laura D / Roberts, Nicholas J. ·Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland. · Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Medical Oncology, Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China, Guangzhou, China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. · The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland. · Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland. · Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland; The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland. · Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland; The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland. · Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland; The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. · Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland; The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland. · Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland; The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: nrobert8@jhmi.edu. ·Gastroenterology · Pubmed #30716324.

ABSTRACT: BACKGROUND & AIMS: Many patients with pancreatic adenocarcinoma carry germline mutations associated with increased risk of cancer. It is not clear whether patients with intraductal papillary mucinous neoplasms (IPMNs), which are precursors to some pancreatic cancers, also carry these mutations. We assessed the prevalence of germline mutations associated with cancer risk in patients with histologically confirmed IPMN. METHODS: We obtained nontumor tissue samples from 315 patients with surgically resected IPMNs from 1997 through 2017, and we sequenced 94 genes with variants associated with cancer risk. Mutations associated with increased risk of cancer were identified and compared with individuals from the Exome Aggregation Consortium. RESULTS: We identified 23 patients with a germline mutation associated with cancer risk (7.3%; 95% confidence interval, 4.9-10.8). Nine patients had a germline mutation associated with pancreatic cancer susceptibility (2.9%; 95% confidence interval, 1.4-5.4). More patients with IPMNs carried germline mutations in ATM (P < .0001), PTCH1 (P < .0001), and SUFU (P < .0001) compared with controls. Patients with IPMNs and germline mutations associated with pancreatic cancer were more like to have concurrent invasive pancreatic carcinoma compared with patients with IPMNs without these mutations (P < .0320). CONCLUSIONS: In sequence analyses of 315 patients with surgically resected IPMNs, we found that almost 3% to carry mutations associated with pancreatic cancer risk. More patients with IPMNs and germline mutations associated with pancreatic cancer had concurrent invasive pancreatic carcinoma compared with patients with IPMNs without these mutations. Genetic analysis of patients with IPMNs might identify those at greatest risk for cancer.

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