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Pancreatic Neoplasms: HELP
Articles by Michael G. Goggins
Based on 148 articles published since 2009
(Why 148 articles?)
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Between 2009 and 2019, M. Goggins wrote the following 148 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 / Anonymous4730741. ·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 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.

6 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.

7 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.

8 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.

9 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.

10 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.

11 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.

12 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 --

13 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

14 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.

15 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;

16 Article Histomorphology of pancreatic cancer in patients with inherited ATM serine/threonine kinase pathogenic variants. 2019

Hutchings, Danielle / Jiang, Zhengdong / Skaro, Michael / Weiss, Matthew J / Wolfgang, Christopher L / Makary, Martin A / He, Jin / Cameron, John L / Zheng, Lei / Klimstra, David S / Brand, Randall E / Singhi, Aatur D / Goggins, Michael / Klein, Alison P / Roberts, Nicholas J / Hruban, Ralph H. ·Department of Pathology, the Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China. · Department of Surgery, the Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Oncology, the Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Department of Medicine, University of Pittsburgh Medical Center Health System, Pittsburgh, PA, USA. · Department of Pathology, University of Pittsburgh Medical Center Health System, Pittsburgh, PA, USA. · Department of Pathology, the Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins University School of Medicine, Baltimore, MD, USA. nrobert8@jhmi.edu. · Department of Oncology, the Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins University School of Medicine, Baltimore, MD, USA. nrobert8@jhmi.edu. · Department of Pathology, the Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins University School of Medicine, Baltimore, MD, USA. rhruban@jhmi.edu. · Department of Oncology, the Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins University School of Medicine, Baltimore, MD, USA. rhruban@jhmi.edu. ·Mod Pathol · Pubmed #31285527.

ABSTRACT: Germline pathogenic variants in the ATM serine/threonine kinase (ATM) gene are associated with an increased risk of pancreatic ductal adenocarcinoma. It is important to identify germline ATM pathogenic variants in pancreatic cancer patients because these alterations are potentially targetable with chemotherapeutic drugs and/or radiation and have implications for other family members. As germline pathogenic variants in other genes have been associated with distinct histologic subtypes of pancreatic cancer, we studied the histomorphology of pancreatic cancer in 23 patients with germline ATM pathogenic variants. The histologic subtype was ductal adenocarcinoma in 19/23 (83%) of the patients, adenosquamous carcinoma in 1/23 (4%), and colloid (mucinous non-cystic) carcinoma in 3/23 (13%). The percentage of colloid (mucinous non-cystic) carcinomas is higher than we have previously observed in patients with familial and sporadic pancreatic cancer (1 and 2% in prior reports, p < 0.01 and p < 0.01, respectively). Three carcinomas (2 colloid carcinomas, 1 ductal adenocarcinoma) arose in association with intraductal papillary mucinous neoplasms. Among the resected pancreata, non-invasive precursor lesions, including pancreatic intraepithelial neoplasia and incipient intraductal papillary mucinous neoplasms, were identified in 83%. We conclude that pancreatic cancers in patients with germline ATM pathogenic variants are more frequently of colloid (mucinous non-cystic) morphology but are overall morphologically diverse supporting the utility of universal germline genetic testing for patients with pancreatic cancer.

17 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.

18 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.

19 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.

20 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.

21 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.

22 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.

23 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.

24 Article Risk of Neoplastic Progression in Individuals at High Risk for Pancreatic Cancer Undergoing Long-term Surveillance. 2018

Canto, Marcia Irene / Almario, Jose Alejandro / Schulick, Richard D / Yeo, Charles J / Klein, Alison / Blackford, Amanda / Shin, Eun Ji / Sanyal, Abanti / Yenokyan, Gayane / Lennon, Anne Marie / Kamel, Ihab R / Fishman, Elliot K / Wolfgang, Christopher / Weiss, Matthew / Hruban, Ralph H / Goggins, Michael. ·Department of Medicine (Gastroenterology), The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland; Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland. Electronic address: mcanto@jhmi.edu. · Department of Medicine (Gastroenterology), The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland; Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland. · Department of Surgery, University of Colorado School of Medicine, Denver, Colorado. · Department of Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania. · Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland. · Department of Medicine (Gastroenterology), The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland. · The Johns Hopkins Biostatistics Center, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. · Department of Radiology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland. · Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland. · Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland. ·Gastroenterology · Pubmed #29803839.

ABSTRACT: BACKGROUND & AIMS: Screening of individuals who have a high risk of pancreatic ductal adenocarcinoma (PDAC), because of genetic factors, frequently leads to identification of pancreatic lesions. We investigated the incidence of PDAC and risk factors for neoplastic progression in individuals at high risk for PDAC enrolled in a long-term screening study. METHODS: We analyzed data from 354 individuals at high risk for PDAC (based on genetic factors of family history), enrolled in Cancer of the Pancreas Screening cohort studies at tertiary care academic centers from 1998 through 2014 (median follow-up time, 5.6 years). All subjects were evaluated at study entry (baseline) by endoscopic ultrasonography and underwent surveillance with endoscopic ultrasonography, magnetic resonance imaging, and/or computed tomography. The primary endpoint was the cumulative incidence of PDAC, pancreatic intraepithelial neoplasia grade 3, or intraductal papillary mucinous neoplasm with high-grade dysplasia (HGD) after baseline. We performed multivariate Cox regression and Kaplan-Meier analyses. RESULTS: During the follow-up period, pancreatic lesions with worrisome features (solid mass, multiple cysts, cyst size > 3 cm, thickened/enhancing walls, mural nodule, dilated main pancreatic duct > 5 mm, or abrupt change in duct caliber) or rapid cyst growth (>4 mm/year) were detected in 68 patients (19%). Overall, 24 of 354 patients (7%) had neoplastic progression (14 PDACs and 10 HGDs) over a 16-year period; the rate of progression was 1.6%/year, and 93% had detectable lesions with worrisome features before diagnosis of the PDAC or HGD. Nine of the 10 PDACs detected during routine surveillance were resectable; a significantly higher proportion of patients with resectable PDACs survived 3 years (85%) compared with the 4 subjects with symptomatic, unresectable PDACs (25%), which developed outside surveillance (log rank P < .0001). Neoplastic progression occurred at a median age of 67 years; the median time from baseline screening until PDAC diagnosis was 4.8 years (interquartile range, 1.6-6.9 years). CONCLUSIONS: In a long-term (16-year) follow-up study of individuals at high-risk for PDAC, we found most PDACs detected during surveillance (9/10) to be resectable, and 85% of these patients survived for 3 years. We identified radiologic features associated with neoplastic progression.

25 Article Genome-Wide Somatic Copy Number Alterations and Mutations in High-Grade Pancreatic Intraepithelial Neoplasia. 2018

Hata, Tatsuo / Suenaga, Masaya / Marchionni, Luigi / Macgregor-Das, Anne / Yu, Jun / Shindo, Koji / Tamura, Koji / Hruban, Ralph H / Goggins, Michael. ·Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. · Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. · Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. · Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. · Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Medicine, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: mgoggins@jhmi.edu. ·Am J Pathol · Pubmed #29684357.

ABSTRACT: To obtain a better understanding of the genetic alterations of high-grade pancreatic intraepithelial neoplasia (HG-PanIN), we performed whole-genome copy number analysis by using single nucleotide polymorphism microarrays and targeted next-generation sequencing of 11 microdissected HG-PanIN and two low-grade PanIN lesions associated with HG-PanIN. HG-PanIN mutation profiles were compared with those of their associated invasive pancreatic ductal adenocarcinoma. All PanIN lesions harbored somatic KRAS mutations. The most common copy number losses in the HG-PanIN were at the CDKN2A (9p21), TP53 (17p13), and SMAD4 (18q21) loci. Chromosomal losses in HG-PanIN were also found at 6p25-p24, 6q11-q27, 12q24, and 17q23-q24. Biallelic inactivation of CDKN2A and TP53 was detected in five of eight and in three of eight evaluable PanIN lesions, respectively. None of the HG-PanIN lesions had SMAD4 mutations or homozygous deletion. Copy number gains were noted at the MYC (8q24) and CCNE1 (19q12) loci and at 1q25-q31. Four HG-PanINs and one low-grade PanIN harbored chromothripsis-like regions. Five of seven pancreatic ductal adenocarcinomas evaluated had additional mutations that were not found in their associated HG-PanIN. HG-PanIN harbors widespread copy number alterations and commonly shows evidence of biallelic inactivation of CDKN2A and TP53 but not SMAD4. Chromothripsis events contribute to the copy number alterations of HG-PanIN.

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