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Pancreatic Neoplasms: HELP
Articles by Anne-Marie Lennon
Based on 60 articles published since 2010
(Why 60 articles?)
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Between 2010 and 2020, A. Lennon wrote the following 60 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Guideline ACG Clinical Guideline: Diagnosis and Management of Pancreatic Cysts. 2018

Elta, Grace H / Enestvedt, Brintha K / Sauer, Bryan G / Lennon, Anne Marie. ·Division of Gastroenterology, University of Michigan Medical Center, Ann Arbor, Michigan, USA. · Division of Gastroenterology, Oregon Health and Sciences University, Portland, Oregon, USA. · Division of Gastroenterology, University of Virginia, Charlottesville, Virginia, USA. · Division of Gastroenterology, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA. ·Am J Gastroenterol · Pubmed #29485131.

ABSTRACT: Pancreatic cysts are very common with the majority incidentally identified. There are several types of pancreatic cysts; some types can contain cancer or have malignant potential, whereas others are benign. However, even the types of cysts with malignant potential rarely progress to cancer. At the present time, the only viable treatment for pancreatic cysts is surgical excision, which is associated with a high morbidity and occasional mortality. The small risk of malignant transformation, the high risks of surgical treatment, and the lack of high-quality prospective studies have led to contradictory recommendations for their immediate management and for their surveillance. This guideline will provide a practical approach to pancreatic cyst management and recommendations for cyst surveillance for the general gastroenterologist.

2 Editorial Chronic pancreatitis-like changes in individuals at high risk for the development of pancreatic cancer: What is the significance? 2019

Brewer Gutierrez, Olaya I / Lennon, Anne Marie. ·Division of Gastroenterology and Hepatology, Johns Hopkins Medical Institution, Baltimore, Maryland, USA. ·Gastrointest Endosc · Pubmed #30902206.

ABSTRACT: -- No abstract --

3 Review Pancreatic Cysts: Sinister Findings or Incidentalomas? 2019

Brewer Gutierrez, Olaya I / Lennon, Anne Marie. ·Division of Gastroenterology and Hepatology, Johns Hopkins Medical Institution, The Johns Hopkins Hospital, Sheikh Zayed Building, 1800 Orleans Street, Suite M2058, Baltimore, MD 21287, USA. · Medicine, Multidisciplinary Pancreatic Cyst Clinic, The Johns Hopkins Medical Institutions, 1800 Orleans Street, Room 7125J, Baltimore, MD 21231, USA; Surgery, Multidisciplinary Pancreatic Cyst Clinic, The Johns Hopkins Medical Institutions, 1800 Orleans Street, Room 7125J, Baltimore, MD 21231, USA; Oncology, Multidisciplinary Pancreatic Cyst Clinic, The Johns Hopkins Medical Institutions, 1800 Orleans Street, Room 7125J, Baltimore, MD 21231, USA; Radiology, Multidisciplinary Pancreatic Cyst Clinic, The Johns Hopkins Medical Institutions, 1800 Orleans Street, Room 7125J, Baltimore, MD 21231, USA. Electronic address: amlennon@jhmi.edu. ·Med Clin North Am · Pubmed #30466673.

ABSTRACT: Pancreatic cysts are common and are incidentally detected in up to 13.5% of individuals. Intraductal papillary mucinous neoplasm (IPMN) and mucinous cystic neoplasm (MCN) are precursors to pancreatic adenocarcinoma. Most will never develop into pancreatic cancer. Several types of pancreatic cysts have no malignant potential. Solid tumors can present as a pancreatic cysts. Guidelines recommend surveillance. Management includes differentiating IPMNs and MCNs from other types, identifying those at highest risk of harboring pancreatic cancer or high-grade dysplasia, and referral to a multidisciplinary group for evaluation and consideration of surgical resection.

4 Review Lessons learned from 29 lymphoepithelial cysts of the pancreas: institutional experience and review of the literature. 2018

Groot, Vincent P / Thakker, Sameer S / Gemenetzis, Georgios / Noë, Michaël / Javed, Ammar A / Burkhart, Richard A / Noveiry, Behnoud B / Cameron, John L / Weiss, Matthew J / VandenBussche, Christopher J / Fishman, Elliot K / Hruban, Ralph H / Wolfgang, Christopher L / Lennon, Anne Marie / He, Jin. ·Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Surgery, UMC Utrecht Cancer Center, University Medical Center Utrecht, Utrecht, The Netherlands. · Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Gastroenterology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Radiology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Gastroenterology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Radiology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: jhe11@jhmi.edu. ·HPB (Oxford) · Pubmed #29530477.

ABSTRACT: BACKGROUND: Lymphoepithelial cysts (LECs) are rare pancreatic cystic lesions. Since LECs are benign, preoperative diagnosis is important to differentiate from a cystic neoplasm and avoid unnecessary surgery. The aim of this study was to identify clinical, radiographic and cytopathologic features associated with LECs. METHODS: A retrospective review was performed of patients diagnosed with LEC between 1995 and 2017 at our hospital. Clinicopathologic and radiographic imaging features were documented. RESULTS: Of 29 patients with pancreatic LEC, 22 underwent surgical resection. The majority were male (n = 24) with a median age of 55 years (range, 21-74). During the evaluation, all patients underwent a CT, with endoscopic ultrasound (EUS) guided fine needle aspiration (FNA) biopsy (n = 22) and/or MRI/MRCP (n = 11) performed in a smaller number of patients. A combination of exophytic tumor growth on imaging and the presence of specific cytomorphologic features on the EUS-FNA cytology biopsy led to the correct diagnosis of LEC and prevention of unnecessary surgery in 7 patients. DISCUSSION: Differentiating LECs from premalignant pancreatic cystic neoplasms remains difficult. Findings of an exophytic growth pattern of the lesion on abdominal imaging and the presence of specific cytomorphologic features in the EUS-FNA biopsy could help clinicians diagnose LEC preoperatively.

5 Review Pancreatic Cysts - Part 2: Should We Be Less Cyst Centric? 2017

Lennon, Anne Marie / Canto, Marcia Irene. ·From the Department of Medicine, Division of Gastroenterology, The Johns Hopkins Medical Institutions, Baltimore, MD. ·Pancreas · Pubmed #28609361.

ABSTRACT: The management of pancreatic cysts is a common problem faced by physicians and surgeons. Pancreatic cysts are important because some of them are mucin-producing cysts (MPCs), which may harbor or develop pancreatic ductal adenocarcinoma. Thus, accurate classification of pancreatic cysts and diagnosis of MPCs offer a potential for the prevention or early detection of pancreatic cancer. However, the diagnosis and management of asymptomatic pancreatic cysts are complicated by 2 factors. First, incidentally detected pancreatic cysts are often misdiagnosed as branch duct intraductal papillary mucinous neoplasms. Although most are MPCs, there are other types of cysts, such as serous cystadenomas, which are managed differently. Second, only a minority of MPCs will ultimately develop into invasive pancreatic ductal adenocarcinoma. Thus, on the one hand, pancreatic cysts offer a unique opportunity to identify precursors to pancreatic cancer and improve outcomes. On the other hand, misdiagnosis and overzealous testing or unnecessary surgery may lead to high cost and harm to patients. Several guidelines have been developed by various groups for the management of pancreatic cysts. In this article, we review the strengths and weaknesses of the American Gastroenterology Association guidelines, highlight key recommendations requiring further validation, and provide our balanced approach to diagnosing and managing pancreatic cysts.

6 Review Solid-pseudopapillary neoplasm of the pancreas: cytomorphologic findings and literature review. 2014

Bhatnagar, Ramneesh / Olson, Matthew T / Fishman, Elliot K / Hruban, Ralph H / Lennon, Anne M / Ali, Syed Z. ·Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Md., USA. ·Acta Cytol · Pubmed #24969629.

ABSTRACT: BACKGROUND: Solid-pseudopapillary neoplasm (SPN) is a rare pancreatic malignancy with an excellent prognosis. It is most commonly diagnosed in young women. This article comprehensively reviews the clinical, pathological and radiological features of this neoplasm, as well as its clinical management. METHODS: A literature review of SPN was performed of all articles published in the English language in PubMed prior to November 1, 2013. Cytomorphological features, histopathology, immunohistochemistry, patient general demographics, molecular studies, radiologic imaging and clinical management were reviewed. RESULTS: SPN displays distinct cytomorphological features on fine-needle aspiration - thin, delicate, branching vessels in a 'Chinese character' pattern lined by one to several layers of loosely cohesive neoplastic cells. Nuclear features include indented or grooved nuclei with an evenly distributed chromatin pattern and small inconspicuous nucleoli. SPN is characteristically immunoreactive for CD10, β-catenin (in an abnormal nuclear pattern), CD99 in a perinuclear dot-like pattern, α1-antitrypsin, and progesterone receptor. Almost all SPNs harbor an activating point mutation in exon 3 of the β-catenin gene (CTNNB1). Clinicopathological features generally do not correlate with prognosis, and most patients experience excellent long-term survival. CONCLUSIONS: SPN can mimic other neoplasms of the pancreas, which can lead to diagnostic challenges in a limited cytologic specimen. Distinct cytomorphological features can help distinguish SPNs from other pancreatic neoplasms. Complete surgical resection as well as resection of metastatic disease is preferred given a low rate of tumor recurrence and long periods of disease-free intervals.

7 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.

8 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.

9 Review Management of pancreatic cysts: a multidisciplinary approach. 2013

Law, Joanna K / Hruban, Ralph H / Lennon, Anne Marie. ·Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. ·Curr Opin Gastroenterol · Pubmed #23872487.

ABSTRACT: PURPOSE OF REVIEW: An increasing number of patients are being diagnosed with pancreatic cysts. Pancreatic cysts are best evaluated by a team of healthcare professionals that includes gastroenterologists, surgeons, radiologists, pathologists, oncologists and geneticists. RECENT FINDINGS: The international consensus guidelines for the management of intraductal papillary mucinous neoplasm (IPMN) and mucinous cystic neoplasm were updated in 2012, incorporating research that had been reported over a 5-year span since the publication of the previous guidelines. There are significant changes in the new guidelines, which include redefining main duct IPMN and removing the recommendation for surgical resection based on size alone. In addition, the discovery of molecular markers of cyst type promises to revolutionize the way patients are diagnosed and managed. SUMMARY: The diagnosis and management of patients with pancreatic cysts have progressed significantly in recent years. Large prospective, multicenter trials are now needed to validate the new international consensus guidelines and to assess the accuracy of new molecular markers.

10 Review Precancerous lesions of the pancreas. 2013

Zamboni, Giuseppe / Hirabayashi, Kenichi / Castelli, Paola / Lennon, Anne Marie. ·Department of Pathology, University of Verona, Verona, Italy; Department of Pathology, Ospedale Sacro Cuore-Don Calabria, Via don Sempreboni, 5, Negrar, 37024 Verona, Italy. giuseppe.zamboni@sacrocuore.it ·Best Pract Res Clin Gastroenterol · Pubmed #23809247.

ABSTRACT: Pancreatic cancer has a very poor prognosis, with a five year survival of only 5%. New studies have shown that it takes over 11 years for cells to develop invasive capability. This provides an opportunity to intervene if precursor lesions can be detected. This paper reviews the molecular, pathological, clinical findings and management of pancreatic intraepithelial neoplasia (PanIN), intraductal pancreatic mucinous neoplasm (IPMN) and mucinous cystic neoplasm (MCN), three precursor lesions which can give rise to invasive carcinoma of the pancreas.

11 Review Cystic neoplasms of the pancreas. 2013

Lennon, Anne Marie / Wolfgang, Christopher. ·The Johns Hopkins Hospital, Baltimore, MD, USA. amlennon@jhmi.edu ·J Gastrointest Surg · Pubmed #23340991.

ABSTRACT: Pancreatic cysts are being identified with increasing frequency due to a combination of increased awareness and more frequent use of cross sectional imaging. Cystic neoplasms of the pancreas range from completely benign to frankly malignant. Identifying pre-malignant cysts offers the opportunity to prevent the development of pancreatic cancer. This article reviews the presentation, workup, and non-operative and operative management of premalignant and malignant pancreatic cysts.

12 Clinical Trial Stylet slow-pull versus standard suction for endoscopic ultrasound-guided fine-needle aspiration of solid pancreatic lesions: a multicenter randomized trial. 2018

Saxena, Payal / El Zein, Mohamad / Stevens, Tyler / Abdelgelil, Ahmed / Besharati, Sepideh / Messallam, Ahmed / Kumbhari, Vivek / Azola, Alba / Brainard, Jennifer / Shin, Eun Ji / Lennon, Anne Marie / Canto, Marcia I / Singh, Vikesh K / Khashab, Mouen A. ·Division of Gastroenterology, Department of Medicine, Johns Hopkins Hospital, Baltimore, Maryland, United States. · Division of Gastroenterology, Department of Medicine, Royal Prince Alfred Hospital, Sydney, Australia. · Digestive Disease Institute, Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, Ohio, United States. · Pathology and Laboratory Medicine Institute, Department of Anatomic Pathology, Cleveland Clinic, Cleveland, Ohio, United States. ·Endoscopy · Pubmed #29272906.

ABSTRACT: BACKGROUND AND STUDY AIM: Standard endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) procedures involve use of no-suction or suction aspiration techniques. A new aspiration method, the stylet slow-pull technique, involves slow withdrawal of the needle stylet to create minimum negative pressure. The aim of this study was to compare the sensitivity of EUS-FNA using stylet slow-pull or suction techniques for malignant solid pancreatic lesions using a standard 22-gauge needle. PATIENTS AND METHODS: Consecutive patients presenting for EUS-FNA of pancreatic mass lesions were randomized to the stylet slow-pull or suction techniques using a 22-gauge needle. Both techniques were standardized for each pass until an adequate specimen was obtained, as determined by rapid on-site cytology examination. Patients were crossed over to the alternative technique after four nondiagnostic passes. RESULTS: Of 147 patients screened, 121 (mean age 64 ± 13.8 years) met inclusion criteria and were randomized to the stylet slow-pull technique (n = 61) or the suction technique (n = 60). Technical success rates were 96.7 % and 98.3 % in the slow-pull and suction groups, respectively ( CONCLUSIONS: The stylet slow-pull and suction techniques both offered high and comparable diagnostic sensitivity with a mean of 2 passes required for diagnosis of solid pancreatic lesions. The endosonographer may choose either technique during FNA.

13 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.

14 Article Recurrent Rearrangements in PRKACA and PRKACB in Intraductal Oncocytic Papillary Neoplasms of the Pancreas and Bile Duct. 2020

Singhi, Aatur D / Wood, Laura D / Parks, Emma / Torbenson, Michael S / Felsenstein, Matthäus / Hruban, Ralph H / Nikiforova, Marina N / Wald, Abigail I / Kaya, Cihan / Nikiforov, Yuri E / Favazza, Laura / He, Jin / McGrath, Kevin / Fasanella, Kenneth E / Brand, Randall E / Lennon, Anne Marie / Furlan, Alessandro / Dasyam, Anil K / Zureikat, Amer H / Zeh, Herbert J / Lee, Kenneth / Bartlett, David L / Slivka, Adam. ·Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; Pittsburgh Liver Research Center, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. Electronic address: singhiad@upmc.edu. · Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland. · Carnegie Mellon University, Pittsburgh, Pennsylvania. · Department of Laboratory Medicine and Pathology, Mayo Clinic Rochester, Rochester, Minnesota. · Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Surgery, Charité-Universitätsmedizin Berlin, Berlin, Germany. · Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. · Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland. · Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. · Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland. · Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. · Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. · Department of Surgery, University of Texas Southwestern, Dallas, Texas. ·Gastroenterology · Pubmed #31678302.

ABSTRACT: BACKGROUND & AIMS: Intraductal oncocytic papillary neoplasms (IOPNs) of the pancreas and bile duct contain epithelial cells with numerous, large mitochondria and are cystic precursors to pancreatic ductal adenocarcinoma (PDAC) and cholangiocarcinoma (CCA), respectively. However, IOPNs do not have the genomic alterations found in other pancreatobiliary neoplasms. In fact, no recurrent genomic alterations have been described in IOPNs. PDACs without activating mutations in KRAS contain gene rearrangements, so we investigated whether IOPNs have recurrent fusions in genes. METHODS: We analyzed 20 resected pancreatic IOPNs and 3 resected biliary IOPNs using a broad RNA-based targeted sequencing panel to detect cancer-related fusion genes. Four invasive PDACs and 2 intrahepatic CCAs from the same patients as the IOPNs, were also available for analysis. Samples of pancreatic cyst fluid (n = 5, collected before surgery) and bile duct brushings (n = 2) were analyzed for translocations. For comparison, we analyzed pancreatobiliary lesions from 126 patients without IOPN (controls). RESULTS: All IOPNs evaluated were found to have recurring fusions of ATP1B1-PRKACB (n = 13), DNAJB1-PRKACA (n = 6), or ATP1B1-PRKACA (n = 4). These fusions also were found in corresponding invasive PDACs and intrahepatic CCAs, as well as in matched pancreatic cyst fluid and bile duct brushings. These gene rearrangements were absent from all 126 control pancreatobiliary lesions. CONCLUSIONS: We identified fusions in PRKACA and PRKACB genes in pancreatic and biliary IOPNs, as well as in PDACs and pancreatic cyst fluid and bile duct cells from the same patients. We did not identify these gene fusions in 126 control pancreatobiliary lesions. These fusions might be used to identify patients at risk for IOPNs and their associated invasive carcinomas.

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

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

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

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

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

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

17 Article Circulating tumor DNA as a potential marker of adjuvant chemotherapy benefit following surgery for localized pancreatic cancer. 2019

Lee, B / Lipton, L / Cohen, J / Tie, J / Javed, A A / Li, L / Goldstein, D / Burge, M / Cooray, P / Nagrial, A / Tebbutt, N C / Thomson, B / Nikfarjam, M / Harris, M / Haydon, A / Lawrence, B / Tai, D W M / Simons, K / Lennon, A M / Wolfgang, C L / Tomasetti, C / Papadopoulos, N / Kinzler, K W / Vogelstein, B / Gibbs, P. ·Division of Systems Biology and Personalised Medicine, Walter & Eliza Hall Institute (WEHI), Melbourne; Department of Medical Oncology, Royal Melbourne Hospital, Melbourne; Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne. Electronic address: lee.b@wehi.edu.au. · Department of Medical Oncology, Royal Melbourne Hospital, Melbourne; Department of Medical Oncology, Western Health, Melbourne; Department of Medical Oncology, Cabrini Health, Malvern, Australia. · Ludwig Centre and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Centre, Baltimore. · Division of Systems Biology and Personalised Medicine, Walter & Eliza Hall Institute (WEHI), Melbourne; Department of Medical Oncology, Royal Melbourne Hospital, Melbourne; Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne; Department of Medical Oncology, Western Health, Melbourne. · Division of Biostatistics and Bioinformatics, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, USA. · Department of Medical Oncology, Prince of Wales Hospital, Randwick. · Department of Medical Oncology, Royal Brisbane Hospital, Brisbane. · Department of Medical Oncology, Eastern Health, Melbourne. · Department of Medical Oncology, Crown Princess Mary Cancer Centre Westmead, Westmead. · Department of Medical Oncology, Olivia Newton-John Cancer and Wellness Centre, Melbourne. · Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne; Department of Surgery, Royal Melbourne Hospital, Melbourne. · Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne; Department of Medical Oncology, Olivia Newton-John Cancer and Wellness Centre, Melbourne. · Department of Medical Oncology, Monash Medical Centre, Clayton. · Department of Medical Oncology, Alfred Hospital, Melbourne, Australia. · Department of Medical Oncology, Auckland City Hospital, Auckland, New Zealand. · Department of Medical Oncology, National Cancer Centre, Singapore. · Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne; Centre for Epidemiology & Biostatistics, University of Melbourne, Melbourne, Australia. · Ludwig Centre and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Centre, Baltimore; Division of Biostatistics and Bioinformatics, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, USA. ·Ann Oncol · Pubmed #31250894.

ABSTRACT: BACKGROUND: In early-stage pancreatic cancer, there are currently no biomarkers to guide selection of therapeutic options. This prospective biomarker trial evaluated the feasibility and potential clinical utility of circulating tumor DNA (ctDNA) analysis to inform adjuvant therapy decision making. MATERIALS AND METHODS: Patients considered by the multidisciplinary team to have resectable pancreatic adenocarcinoma were enrolled. Pre- and post-operative samples for ctDNA analysis were collected. PCR-based-SafeSeqS assays were used to identify mutations at codon 12, 13 and 61 of KRAS in the primary pancreatic tumor and to detect ctDNA. Results of ctDNA analysis were correlated with CA19-9, recurrence-free and overall survival (OS). Patient management was per standard of care, blinded to ctDNA data. RESULTS: Of 112 patients consented pre-operatively, 81 (72%) underwent resection. KRAS mutations were identified in 91% (38/42) of available tumor samples. Of available plasma samples (N = 42), KRAS mutated ctDNA was detected in 62% (23/37) pre-operative and 37% (13/35) post-operative cases. At a median follow-up of 38.4 months, ctDNA detection in the pre-operative setting was associated with inferior recurrence-free survival (RFS) [hazard ratio (HR) 4.1; P = 0.002)] and OS (HR 4.1; P = 0.015). Detectable ctDNA following curative intent resection was associated with inferior RFS (HR 5.4; P < 0.0001) and OS (HR 4.0; P = 0.003). Recurrence occurred in 13/13 (100%) patients with detectable ctDNA post-operatively, including in seven that received gemcitabine-based adjuvant chemotherapy. CONCLUSION: ctDNA studies in localized pancreatic cancer are challenging, with a substantial number of patients not able to undergo resection, not having sufficient tumor tissue for analysis or not completing per protocol sample collection. ctDNA analysis, pre- and/or post-surgery, is a promising prognostic marker. Studies of ctDNA guided therapy are justified, including of treatment intensification strategies for patients with detectable ctDNA post-operatively who appear at very high risk of recurrence despite gemcitabine-based adjuvant therapy.

18 Article Intraductal Papillary Mucinous Neoplasms Arise From Multiple Independent Clones, Each With Distinct Mutations. 2019

Fischer, Catherine G / Beleva Guthrie, Violeta / Braxton, Alicia M / Zheng, Lily / Wang, Pei / Song, Qianqian / Griffin, James F / Chianchiano, Peter E / Hosoda, Waki / Niknafs, Noushin / Springer, Simeon / Dal Molin, Marco / Masica, David / Scharpf, Robert B / Thompson, Elizabeth D / He, Jin / Wolfgang, Christopher L / Hruban, Ralph H / Roberts, Nicholas J / Lennon, Anne Marie / Jiao, Yuchen / Karchin, Rachel / Wood, Laura D. ·Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. · Institute for Computational Medicine, Johns Hopkins University, Baltimore, Maryland; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland. · Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland. · McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland. · State Key Lab of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. · Department of Surgery, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. · Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. · Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; Ludwig Center for Cancer Genetics and Therapeutics, Johns Hopkins University School of Medicine, Baltimore, Maryland. · Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; Sidney Kimmel Comprehensive Cancer 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. · Institute for Computational Medicine, Johns Hopkins University, Baltimore, Maryland; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: karchin@jhu.edu. · Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: ldwood@jhmi.edu. ·Gastroenterology · Pubmed #31175866.

ABSTRACT: BACKGROUND & AIMS: Intraductal papillary mucinous neoplasms (IPMNs) are lesions that can progress to invasive pancreatic cancer and constitute an important system for studies of pancreatic tumorigenesis. We performed comprehensive genomic analyses of entire IPMNs to determine the diversity of somatic mutations in genes that promote tumorigenesis. METHODS: We microdissected neoplastic tissues from 6-24 regions each of 20 resected IPMNs, resulting in 227 neoplastic samples that were analyzed by capture-based targeted sequencing. Somatic mutations in genes associated with pancreatic tumorigenesis were assessed across entire IPMN lesions, and the resulting data were supported by evolutionary modeling, whole-exome sequencing, and in situ detection of mutations. RESULTS: We found a high prevalence of heterogeneity among mutations in IPMNs. Heterogeneity in mutations in KRAS and GNAS was significantly more prevalent in IPMNs with low-grade dysplasia than in IPMNs with high-grade dysplasia (P < .02). Whole-exome sequencing confirmed that IPMNs contained multiple independent clones, each with distinct mutations, as originally indicated by targeted sequencing and evolutionary modeling. We also found evidence for convergent evolution of mutations in RNF43 and TP53, which are acquired during later stages of tumorigenesis. CONCLUSIONS: In an analysis of the heterogeneity of mutations throughout IPMNs, we found that early-stage IPMNs contain multiple independent clones, each with distinct mutations, indicating their polyclonal origin. These findings challenge the model in which pancreatic neoplasms arise from a single clone. Increasing our understanding of the mechanisms of IPMN polyclonality could lead to strategies to identify patients at increased risk for pancreatic cancer.

19 Article Cross Validation of the Monoclonal Antibody Das-1 in Identification of High-Risk Mucinous Pancreatic Cystic Lesions. 2019

Das, Koushik K / Geng, Xin / Brown, Jeffrey W / Morales-Oyarvide, Vicente / Huynh, Tiffany / Pergolini, Ilaria / Pitman, Martha B / Ferrone, Cristina / Al Efishat, Mohammad / Haviland, Dana / Thompson, Elizabeth / Wolfgang, Christopher / Lennon, Anne Marie / Allen, Peter / Lillemoe, Keith D / Fields, Ryan C / Hawkins, William G / Liu, Jingxia / Castillo, Carlos Fernandez-Del / Das, Kiron M / Mino-Kenudson, Mari. ·Division of Gastroenterology, Washington University, St Louis, Missouri. Electronic address: k.das@wustl.edu. · Division of Gastroenterology, Rutgers-Robert Wood Johnson Medical School, New Brunswick, New Jersey. · Division of Gastroenterology, Washington University, St Louis, Missouri. · Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts. · Deparment of Pathology, Massachusetts General Hospital, Boston, Massachusetts. · Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York. · Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland. · Department of Surgery Johns Hopkins School of Medicine, Baltimore, Maryland. · Division of Gastroenterology, Johns Hopkins School of Medicine, Baltimore, Maryland. · Department of Surgery, Washington University, St Louis, Missouri. · Deparment of Pathology, Massachusetts General Hospital, Boston, Massachusetts. Electronic address: mminokenudson@partners.org. ·Gastroenterology · Pubmed #31175863.

ABSTRACT: BACKGROUND & AIMS: Although pancreatic cystic lesions (PCLs) are frequently and incidentally detected, it is a challenge to determine their risk of malignancy. In immunohistochemical and enzyme-linked immunosorbent assay (ELISA) analyses of tissue and cyst fluid from pancreatic intraductal papillary mucinous neoplasms, the monoclonal antibody Das-1 identifies those at risk for malignancy with high levels of specificity and sensitivity. We aimed to validate the ability of Das-1 to identify high-risk PCLs in comparison to clinical guidelines and clinical features, using samples from a multicenter cohort. METHODS: We obtained cyst fluid samples of 169 PCLs (90 intraductal papillary mucinous neoplasms, 43 mucinous cystic neoplasms, and 36 non-mucinous cysts) from patients undergoing surgery at 4 tertiary referral centers (January 2010 through June 2017). Histology findings from surgical samples, analyzed independently and centrally re-reviewed in a blinded manner, were used as the reference standard. High-risk PCLs were those with invasive carcinomas, high-grade dysplasia, or intestinal-type intraductal papillary mucinous neoplasms with intermediate-grade dysplasia. An ELISA with Das-1 was performed in parallel using banked cyst fluid samples. We evaluated the biomarker's performance, generated area under the curve values, and conducted multivariate logistic regression using clinical and pathology features. RESULTS: The ELISA for Das-1 identified high-risk PCLs with 88% sensitivity, 99% specificity, and 95% accuracy, at a cutoff optical density value of 0.104. In 10-fold cross-validation analysis with 100 replications, Das-1 identified high-risk PCLs with 88% sensitivity and 98% specificity. The Sendai, Fukuoka, and American Gastroenterological Association guideline criteria identified high-risk PCLs with 46%, 52%, and 74% accuracy (P for comparison to Das-1 ELISA <.001). When we controlled for Das-1 in multivariate regression, main pancreatic duct dilation >5 mm (odds ratio, 14.98; 95% confidence interval, 2.63-108; P < .0012), main pancreatic duct dilation ≥1 cm (odds ratio, 47.9; 95% confidence interval, 6.39-490; P < .0001), and jaundice (odds ratio, 6.16; 95% confidence interval, 1.08-36.7; P = .0397) were significantly associated with high-risk PCLs. CONCLUSIONS: We validated the ability of an ELISA with the monoclonal antibody Das-1 to detect PCLs at risk for malignancy with high levels of sensitivity and specificity. This biomarker might be used in conjunction with clinical guidelines to identify patients at risk for malignancy.

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

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

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

21 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.

22 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.

23 Article Pancreatic Juice Mutation Concentrations Can Help Predict the Grade of Dysplasia in Patients Undergoing Pancreatic Surveillance. 2018

Suenaga, Masaya / Yu, Jun / Shindo, Koji / Tamura, Koji / Almario, Jose Alejandro / Zaykoski, Christopher / Witmer, P Dane / Fesharakizadeh, Shahriar / Borges, Michael / Lennon, Anne-Marie / Shin, Eun-Ji / Canto, Marcia Irene / Goggins, Michael. ·Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland. · Center for Inherited Disease Research (CIDR), Baltimore, Maryland. · Department of Medicine, 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 Oncology, 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. mgoggins@jhmi.edu. ·Clin Cancer Res · Pubmed #29301828.

ABSTRACT:

24 Article Combined circulating tumor DNA and protein biomarker-based liquid biopsy for the earlier detection of pancreatic cancers. 2017

Cohen, Joshua D / Javed, Ammar A / Thoburn, Christopher / Wong, Fay / Tie, Jeanne / Gibbs, Peter / Schmidt, C Max / Yip-Schneider, Michele T / Allen, Peter J / Schattner, Mark / Brand, Randall E / Singhi, Aatur D / Petersen, Gloria M / Hong, Seung-Mo / Kim, Song Cheol / Falconi, Massimo / Doglioni, Claudio / Weiss, Matthew J / Ahuja, Nita / He, Jin / Makary, Martin A / Maitra, Anirban / Hanash, Samir M / Dal Molin, Marco / Wang, Yuxuan / Li, Lu / Ptak, Janine / Dobbyn, Lisa / Schaefer, Joy / Silliman, Natalie / Popoli, Maria / Goggins, Michael G / Hruban, Ralph H / Wolfgang, Christopher L / Klein, Alison P / Tomasetti, Cristian / Papadopoulos, Nickolas / Kinzler, Kenneth W / Vogelstein, Bert / Lennon, Anne Marie. ·The Ludwig Center, The Johns Hopkins Medical Institutions, Baltimore, MD 21287. · Howard Hughes Medical Institute, The Johns Hopkins Medical Institutions, Baltimore, MD 21287. · Sidney Kimmel Cancer Center at Johns Hopkins, The Johns Hopkins Medical Institutions, Baltimore, MD 21287. · The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Medical Institutions, Baltimore, MD 21287. · Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205. · Department of Surgery, The Johns Hopkins Medical Institutions, Baltimore, MD 21287. · Division of Systems Biology and Personalized Medicine, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3021, Australia. · Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, VIC 3010, Australia. · Department of Medical Oncology, Western Health, Melbourne, VIC 3021, Australia. · Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202. · Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202. · Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10065. · Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065. · Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15260. · Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15260. · Department of Epidemiology, Mayo Clinic, Rochester, MN 55902. · Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea. · Department of Hepatobiliary and Pancreas Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea. · Division of Pancreatic Surgery, Department of Surgery, San Raffaele Scientific Institute Research Hospital, 20132 Milan, Italy. · Department of Pathology, San Raffaele Scientific Institute Research Hospital, 20132 Milan, Italy. · The Sheikh Ahmed Center for Pancreatic Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, TX 77030. · Department of Biostatistics, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205. · Department of Medicine, The Johns Hopkins Medical Institutions, Baltimore, MD 21287. · Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD 21287. · Department of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205. · Division of Biostatistics and Bioinformatics, Department of Oncology, The Johns Hopkins Medical Institutions, Baltimore, MD 21287. · The Ludwig Center, The Johns Hopkins Medical Institutions, Baltimore, MD 21287; bertvog@gmail.com amlennon@jhmi.edu. · The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Medical Institutions, Baltimore, MD 21287; bertvog@gmail.com amlennon@jhmi.edu. ·Proc Natl Acad Sci U S A · Pubmed #28874546.

ABSTRACT: The earlier diagnosis of cancer is one of the keys to reducing cancer deaths in the future. Here we describe our efforts to develop a noninvasive blood test for the detection of pancreatic ductal adenocarcinoma. We combined blood tests for

25 Article Circulating Epithelial Cells in Intraductal Papillary Mucinous Neoplasms and Cystic Pancreatic Lesions. 2017

Poruk, Katherine E / Valero, Vicente / He, Jin / Ahuja, Nita / Cameron, John L / Weiss, Matthew J / Lennon, Anne Marie / Goggins, Michael / Wood, Laura D / Wolfgang, Christopher L. ·From the Departments of *Surgery, †Gastroenterology, and ‡Pathology, The Johns Hopkins Hospital, Baltimore, MD. ·Pancreas · Pubmed #28697136.

ABSTRACT: OBJECTIVES: Circulating epithelial cells (CECs) are identified in the blood of patients with intraductal papillary mucinous neoplasms (IPMNs) despite the absence of malignancy. We assessed the blood of patients undergoing resection for IPMN or other benign pancreatic lesions for CECs. METHODS: Peripheral blood was collected from 26 patients prior to pancreatic resection and filtered by the ISET (Isolation by Size of Epithelial Tumor Cells) method. Circulating epithelial cells were identified with antibodies to cytokeratin and Pdx1 (pancreas and duodenal homeobox protein 1), a pancreas marker. RESULTS: Nineteen patients underwent resection of an IPMN without associated malignancy. Eleven patients (58%) had cytokeratin-positive CECs. Circulating epithelial cells were significantly more likely to be found in patients with IPMNs with high-grade dysplasia (P = 0.04). In addition, 10 of the 11 patients with cytokeratin-positive CECs also had separate populations of cytokeratin-positive, Pdx1-positive CECs, suggesting a pancreatic source. Dual-staining CECs were more frequently found in patients with high-grade dysplasia (P = 0.04). Patients with IPMNs were significantly more likely to have pan-cytokeratin CECs in the blood compared with those without IPMNs (P = 0.01). CONCLUSIONS: Circulating epithelial cells staining with potential pancreas-specific markers have been found in patients with IPMNs, even without malignancy. Circulating epithelial cells may help to differentiate patients with high-grade IPMN from lower grades of dysplasia and other pancreatic cysts.

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