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Pancreatic Neoplasms: HELP
Articles by Michael G. Goggins
Based on 132 articles published since 2010
(Why 132 articles?)
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Between 2010 and 2020, M. Goggins wrote the following 132 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 / Anonymous1461018. ·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 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:

18 Article Surgical Outcomes After Pancreatic Resection of Screening-Detected Lesions in Individuals at High Risk for Developing Pancreatic Cancer. 2019

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.

19 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.

20 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.

21 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.

22 Article Single-cell sequencing defines genetic heterogeneity in pancreatic cancer precursor lesions. 2019

Kuboki, Yuko / Fischer, Catherine G / Beleva Guthrie, Violeta / Huang, Wenjie / Yu, Jun / Chianchiano, Peter / Hosoda, Waki / Zhang, Hao / Zheng, Lily / Shao, Xiaoshan / Thompson, Elizabeth D / Waters, Kevin / Poling, Justin / He, Jin / Weiss, Matthew J / Wolfgang, Christopher L / Goggins, Michael G / Hruban, Ralph H / Roberts, Nicholas J / Karchin, Rachel / Wood, Laura D. ·Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD, USA. · Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA. · Department of Surgery, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA. · McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA. ·J Pathol · Pubmed #30430578.

ABSTRACT: Intraductal papillary mucinous neoplasms (IPMNs) are precursors to pancreatic cancer; however, little is known about genetic heterogeneity in these lesions. The objective of this study was to characterize genetic heterogeneity in IPMNs at the single-cell level. We isolated single cells from fresh tissue from ten IPMNs, followed by whole genome amplification and targeted next-generation sequencing of pancreatic driver genes. We then determined single-cell genotypes using a novel multi-sample mutation calling algorithm. Our analyses revealed that different mutations in the same driver gene frequently occur in the same IPMN. Two IPMNs had multiple mutations in the initiating driver gene KRAS that occurred in unique tumor clones, suggesting the possibility of polyclonal origin or an unidentified initiating event preceding this critical mutation. Multiple mutations in later-occurring driver genes were also common and were frequently localized to unique tumor clones, raising the possibility of convergent evolution of these genetic events in pancreatic tumorigenesis. Single-cell sequencing of IPMNs demonstrated genetic heterogeneity with respect to early and late occurring driver gene mutations, suggesting a more complex pattern of tumor evolution than previously appreciated in these lesions. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

23 Article Blood Type as a Predictor of High-Grade Dysplasia and Associated Malignancy in Patients with Intraductal Papillary Mucinous Neoplasms. 2019

Poruk, Katherine E / Griffin, James / Makary, Martin A / He, Jin / Cameron, John L / Weiss, Matthew J / Wood, Laura D / Goggins, Michael / Wolfgang, Christopher L. ·Department of Surgery, Johns Hopkins Hospital, 600 N. Wolfe Street Osler 624, Baltimore, MD, 21287, USA. · Department of Pathology, Johns Hopkins Hospital, Baltimore, MD, 21287, USA. · Department of Pathology, Johns Hopkins Hospital, Baltimore, MD, 21287, USA. mgoggins@jhmi.edu. · Department of Oncology and Medicine, the Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Hospital, Baltimore, MD, 21287, USA. mgoggins@jhmi.edu. · Department of Surgery, Johns Hopkins Hospital, 600 N. Wolfe Street Osler 624, Baltimore, MD, 21287, USA. cwolfga2@jhmi.edu. ·J Gastrointest Surg · Pubmed #30187322.

ABSTRACT: BACKGROUND: Intraductal papillary mucinous neoplasms (IPMNs) are precursor lesions to the development of pancreatic adenocarcinoma. We determined if non-O blood groups are more common in patients with IPMN and if blood group is a risk factor for progression to invasive pancreatic cancer among patients with IPMN. METHODS: The medical records were reviewed of all patients undergoing resection of an IPMN at Johns Hopkins Hospital from June 1997 to August 2016. Potential risk factors of high-grade dysplasia and associated adenocarcinoma were identified through a multivariate logistic regression model. RESULTS: Seven hundred and seventy-seven patients underwent surgical resection of an IPMN in which preoperative blood type was known. Sixty-two percent of IPMN patients had non-O blood groups (vs. 57% in two large US reference cohorts, P = 0.002). The association between non-O blood group was significant for patients with IPMN with low- or intermediate-grade dysplasia (P < 0.001), not for those with high-grade dysplasia (P = 0.68). Low- and intermediate-grade IPMNs were more likely to have non-type O blood compared to those with high-grade IPMN and/or associated invasive adenocarcinoma (P = 0.045). Blood type O was an independent predictor of having high-grade dysplasia without associated adenocarcinoma (P = 0.02), but not having associated invasive cancer (P = 0.72). The main risk factor for progression to invasive cancer after surgical resection was IPMN with high-grade dysplasia (P = 0.002). CONCLUSION: IPMN patients are more likely to have non-O blood groups than controls, but type O blood group carriers had higher odds of having high-grade dysplasia in their IPMN. These results indicate blood group status may have different effects on the risk and progression of IPMNs.

24 Article Primordial germ cells as a potential shared cell of origin for mucinous cystic neoplasms of the pancreas and mucinous ovarian tumors. 2018

Elias, Kevin M / Tsantoulis, Petros / Tille, Jean-Christophe / Vitonis, Allison / Doyle, Leona A / Hornick, Jason L / Kaya, Gurkan / Barnes, Laurent / Cramer, Daniel W / Puppa, Giacomo / Stuckelberger, Sarah / Hooda, Jagmohan / Dietrich, Pierre-Yves / Goggins, Michael / Kerr, Candace L / Birrer, Michael / Hirsch, Michelle S / Drapkin, Ronny / Labidi-Galy, Sana Intidhar. ·Division of Gynecologic Oncology, Department of Obstetrics and Gynecology and Reproductive Biology, Brigham and Women's Hospital, Boston, MA, USA. · Division of Gynecologic Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. · Harvard Medical School, Boston, MA, USA. · Department of internal medicine specialties, Facutly of Medicine, Université de Genève, Geneva, Switzerland. · Department of Oncology, Hôpitaux Universitaires de Genève, Geneva, Switzerland. · Division of Pathology, Hôpitaux Universitaires de Genève, Geneva, Switzerland. · Department of Obstetrics and Gynecology, Epidemiology Center, Brigham and Women's Hospital, Boston, MA, USA. · Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA. · Division of Dermatology, Hôpitaux Universitaires de Genève, Geneva, Switzerland. · Penn Ovarian Cancer Research Center, Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, PA, USA. · Department of Pathology, Johns Hopkins Hospital, Baltimore, MD, USA. · Department of Biochemistry and Molecular Biology, University of Maryland, Baltimore, MD, USA. · Division of Hematology-Oncology, University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, AL, USA. ·J Pathol · Pubmed #30229909.

ABSTRACT: Mucinous ovarian tumors (MOTs) morphologically and epidemiologically resemble mucinous cystic neoplasms (MCNs) of the pancreas, sharing a similar stroma and both occurring disproportionately among young females. Additionally, MOTs and MCNs share similar clinical characteristics and immunohistochemical phenotypes. Exome sequencing has revealed frequent recurrent mutations in KRAS and RNF43 in both MOTs and MCNs. The cell of origin for these tumors remains unclear, but MOTs sometimes arise in the context of mature cystic teratomas and other primordial germ cell (PGC) tumors. We undertook the present study to investigate whether non-teratoma-associated MOTs and MCNs share a common cell of origin. Comparisons of the gene expression profiles of MOTs [including both the mucinous borderline ovarian tumors (MBOTs) and invasive mucinous ovarian carcinomas (MOCs)], high-grade serous ovarian carcinomas, ovarian surface epithelium, Fallopian tube epithelium, normal pancreatic tissue, pancreatic duct adenocarcinomas, MCNs, and single-cell RNA-sequencing of PGCs revealed that both MOTs and MCNs are more closely related to PGCs than to either eutopic epithelial tumors or normal epithelia. We hypothesize that MCNs may arise from PGCs that stopped in the dorsal pancreas during their descent to the gonads during early human embryogenesis, while MOTs arise from PGCs in the ovary. Together, these data suggest a common pathway for the development of MCNs and MOTs, and suggest that these tumors may be more properly classified as germ cell tumor variants. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

25 Article Clinical and Radiographic Gastrointestinal Abnormalities in McCune-Albright Syndrome. 2018

Robinson, Cemre / Estrada, Andrea / Zaheer, Atif / Singh, Vikesh K / Wolfgang, Christopher L / Goggins, Michael G / Hruban, Ralph H / Wood, Laura D / Noë, Michaël / Montgomery, Elizabeth A / Guthrie, Lori C / Lennon, Anne Marie / Boyce, Alison M / Collins, Michael T. ·Skeletal Disorders and Mineral Homeostasis Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland. · Program in Developmental Endocrinology and Genetics, The Eunice Kennedy Shriver Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland. · Department of Pediatrics, Section of Endocrinology, Yale University School of Medicine, New Haven, Connecticut. · Division of Endocrinology and Diabetes, Children's National Health System, Washington, DC. · Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland. · Division of Gastroenterology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland. · Departments of Surgery, Radiology, and Oncology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland. · Department of Pathology, 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. ·J Clin Endocrinol Metab · Pubmed #30124968.

ABSTRACT: Context: McCune-Albright syndrome (MAS) is a rare disorder characterized by fibrous dysplasia of bone, café-au-lait macules, and hyperfunctioning endocrinopathies. It arises from somatic gain-of-function mutations in GNAS, which encodes the cAMP-regulating protein Gαs. Somatic GNAS mutations have been reported in intraductal papillary mucinous neoplasms (IPMNs) and various gastrointestinal (GI) tumors. The clinical spectrum and prevalence of MAS-associated GI disease is not well established. Objective: Define the spectrum and prevalence of MAS-associated GI pathology in a large cohort of patients with MAS. Design: Cross-sectional study. Setting: National Institutes of Health Clinical Center and The Johns Hopkins Hospital. Methods: Fifty-four consecutive subjects with MAS (28 males; age range, 7 to 67 years) were screened with magnetic resonance cholangiopancreatography (MRCP). Results: Thirty of 54 subjects (56%) had radiographic GI abnormalities. Twenty-five (46%) of the screened subjects had IPMNs (mean age of 35.1 years). Fourteen of the 25 had IPMNs alone, and 11 had IPMNs and abnormal hepatobiliary imaging. The 30 patients with MAS-associated GI pathology had a higher prevalence of acute pancreatitis, diabetes mellitus, and skeletal disease burden of fibrous dysplasia than patients without GI disease. Conclusions: A broad spectrum of GI pathology is associated with MAS. IPMNs are common and occur at a younger age than in the general population. Patients with MAS should be considered for screening with a focused GI history and baseline MRCP. Further determination of the natural history and malignant potential of IPMNs in MAS is needed.

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