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Pancreatic Neoplasms: HELP
Articles by Gabriele Capurso
Based on 67 articles published since 2010
(Why 67 articles?)
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Between 2010 and 2020, G. Capurso wrote the following 67 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Guideline Italian consensus guidelines for the diagnostic work-up and follow-up of cystic pancreatic neoplasms. 2014

Anonymous4770793 / Anonymous4780793 / Buscarini, Elisabetta / Pezzilli, Raffaele / Cannizzaro, Renato / De Angelis, Claudio / Gion, Massimo / Morana, Giovanni / Zamboni, Giuseppe / Arcidiacono, Paolo / Balzano, Gianpaolo / Barresi, Luca / Basso, Daniela / Bocus, Paolo / Calculli, Lucia / Capurso, Gabriele / Canzonieri, Vincenzo / Casadei, Riccardo / Crippa, Stefano / D'Onofrio, Mirko / Frulloni, Luca / Fusaroli, Pietro / Manfredi, Guido / Pacchioni, Donatella / Pasquali, Claudio / Rocca, Rodolfo / Ventrucci, Maurizio / Venturini, Silvia / Villanacci, Vincenzo / Zerbi, Alessandro / Falconi, Massimo / Anonymous4790793. ·Gastroenterology Unit, Maggiore Hospital, Crema, Italy. Electronic address: ebuscarini@rim.it. · Pancreas Unit, Department of Digestive Diseases and Internal Medicine, S. Orsola-Malpighi Hospital, Bologna, Italy. · Gastroenterology Unit, CRO-National Cancer Institute, Aviano, Italy. · Gastroenterology and Hepatology Department, A.O. San Giovanni Battista/Molinette, University of Turin, Turin, Italy. · Department of Clinical Pathology, AULSS 12, Venice, Italy. · Department of Diagnostic Radiology, Ospedale Cà Foncello, Treviso, Italy. · Department of Pathology, University of Verona, Verona, Italy. · Division of Gastroenterology and Gastrointestinal Endoscopy, Vita-Salute, Italy. · Department of Surgery, San Raffaele Scientific Institute, Milan, Italy. · Gastroenterology and Endoscopy Unit, ISMETT, Palermo, Italy. · Department of Laboratory Medicine, University Hospital, Padua, Italy. · Gastroenterology Unit, Ospedale Sacro Cuore-Don Calabria, Negrar, Verona, Italy. · Department of Radiology, S. Orsola-Malpighi Hospital, Bologna, Italy. · Digestive and Liver Disease Unit, Faculty of Medicine and Psychology, Sapienza University of Rome at S. Andrea Hospital, Rome, Italy. · Division of Pathology, CRO-National Cancer Institute, IRCCS, Aviano, Italy. · Department of Surgery, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy. · Department of Surgery, Pancreas Unit, Università Politecnica delle Marche, Ancona, Italy. · Department of Radiology, University Hospital G.B. Rossi, University of Verona, Verona, Italy. · Department of Surgical and Gastroenterological Sciences, University of Verona, Verona, Italy. · Department of Clinical Medicine, University of Bologna, Bologna, Italy. · Gastroenterology Unit, Maggiore Hospital, Crema, Italy. · Pathology Unit, A.O. San Giovanni Battista/Molinette, Turin, Italy. · Surgery Unit IV, Department of Medical and Surgical Sciences, University of Padua, Padua, Italy. · Gastroenterology Unit, Mauriziano Hospital, Turin, Italy. · Department of Internal Medicine and Gastroenterology, Bentivoglio Hospital, Bologna, Italy. · 2nd Pathology Section, Spedali Civili, Brescia, Brescia, Italy. · Pancreatic Surgery, Department of Surgery, Humanitas Clinical and Research Center, Milan, Italy. ·Dig Liver Dis · Pubmed #24809235.

ABSTRACT: This report contains clinically oriented guidelines for the diagnostic work-up and follow-up of cystic pancreatic neoplasms in patients fit for treatment. The statements were elaborated by working groups of experts by searching and analysing the literature, and then underwent a consensus process using a modified Delphi procedure. The statements report recommendations regarding the most appropriate use and timing of various imaging techniques and of endoscopic ultrasound, the role of circulating and intracystic markers and the pathologic evaluation for the diagnosis and follow-up of cystic pancreatic neoplasms.

2 Guideline Familial pancreatic cancer in Italy. Risk assessment, screening programs and clinical approach: a position paper from the Italian Registry. 2010

Del Chiaro, Marco / Zerbi, Alessandro / Capurso, Gabriele / Zamboni, Giuseppe / Maisonneuve, Patrick / Presciuttini, Silvano / Arcidiacono, Paolo Giorgio / Calculli, Lucia / Falconi, Massimo / Anonymous7420665. ·Division of General and Transplant Surgery, Pisa University Hospital, Via Paradisa 2, 56124 Cisanello, Pisa, Italy. m.delchiaro@ao-pisa.toscana.it ·Dig Liver Dis · Pubmed #20627831.

ABSTRACT: In Italy, pancreatic cancer is the fifth leading cause of tumor related death with about 7000 new cases per year and a mortality rate of 95%. In a recent prospective epidemiological study on the Italian population, a family history was found in about 10% of patients suffering from a ductal adenocarcinoma of the pancreas (PDAC). A position paper from the Italian Registry for Familial Pancreatic Cancer was made to manage these high-risk individuals. Even though in the majority of high-risk individuals a genetic test to identify familial predisposition is not available, a screening protocol seems to be reasonable for subjects who have a >10-fold greater risk for the development of PDAC. However this kind of screening should be included in clinical trials, performed in centers with high expertise in pancreatic disease, using the least aggressive diagnostic modalities.

3 Editorial New era for pancreatic endoscopic ultrasound: From imaging to molecular pathology of pancreatic cancer. 2019

Archibugi, Livia / Testoni, Sabrina Gloria Giulia / Redegalli, Miriam / Petrone, Maria Chiara / Reni, Michele / Falconi, Massimo / Doglioni, Claudio / Capurso, Gabriele / Arcidiacono, Paolo Giorgio. ·Pancreato-Biliary Endoscopy and EUS Division, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan 20132, Italy. · Pathology Department, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan 20132, Italy. · Department of Medical Oncology, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan 20132, Italy. · Pancreatic Surgery Department, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan 20132, Italy. · Pancreato-Biliary Endoscopy and EUS Division, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan 20132, Italy. capurso.gabriele@hsr.it. ·World J Gastrointest Oncol · Pubmed #31798775.

ABSTRACT: With recent advances in molecular pathology and the development of new chemotherapy regimens, the knowledge of the molecular alterations of pancreatic ductal adenocarcinoma (PDAC) is becoming appealing for stratifying patients for prognosis and response to a defined treatment. Archival formalin-fixed, paraffin-embedded samples are a useful source of genomic deoxyribonucleic acid; nevertheless, most studies employed formalin-fixed, paraffin-embedded samples deriving from surgical specimens, which are therefore representative of <20% of PDAC patients. Indeed, the development of a reliable methodology for endoscopic ultrasound-guided tissue acquisition, stabilization, and analysis is crucial for the development of molecular markers for clinical use in order to achieve "personalized medicine". With the development of new needles, this technique is able to retrieve a high quantity and quality of PDAC tissue that can be used not only for diagnosis but also for mutational and transcriptome evaluations and for the development of primary cell or tissue cultures. In the present editorial, we discuss the current knowledge regarding the use of endoscopic ultrasound as a tool to obtain samples for molecular analyses, its possible pitfalls, and its use for the development of disease models such as xenografts or organoids.

4 Review Pancreatic Enzyme Replacement Therapy in Pancreatic Cancer. 2020

Pezzilli, Raffaele / Caccialanza, Riccardo / Capurso, Gabriele / Brunetti, Oronzo / Milella, Michele / Falconi, Massimo. ·Gastroenterology Unit, San Carlo Hospital, Via P. Petrone, 85100 Potenza, Italy. · Clinical Nutrition and Dietetics Unit, Fondazione IRCCS Policlinico San Matteo, Viale Camillo Golgi 19, 27100 Pavia, Italy. · Clinical Research, Pancreato-Biliary Endoscopy and EUS Division, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milano, Italy. · Medical Oncology Unit, National Cancer Institute "Giovanni Paolo II", Viale O. Flacco 65, 70124 Bari, Italy. · Residency Program in Medical Oncology, University of Verona, Via S. Francesco 22, 37129 Verona, Italy. · AOUI Verona, Sede Policlinico Universitario G.B. Rossi Borgo Roma, P.le L.A. Scuro 10, 37134 Verona, Italy. · Pancreatic Surgery, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milano, Italy. ·Cancers (Basel) · Pubmed #31979186.

ABSTRACT: Pancreatic cancer is an aggressive malignancy and the seventh leading cause of global cancer deaths in industrialised countries. More than 80% of patients suffer from significant weight loss at diagnosis and over time tend to develop severe cachexia. A major cause of weight loss is malnutrition. Patients may experience pancreatic exocrine insufficiency (PEI) before diagnosis, during nonsurgical treatment, and/or following surgery. PEI is difficult to diagnose because testing is cumbersome. Consequently, PEI is often detected clinically, especially in non-specialised centres, and treated empirically. In this position paper, we review the current literature on nutritional support and pancreatic enzyme replacement therapy (PERT) in patients with operable and non-operable pancreatic cancer. To increase awareness on the importance of PERT in pancreatic patients, we provide recommendations based on literature evidence, and when data were lacking, based on our own clinical experience.

5 Review Exocrine pancreatic insufficiency: prevalence, diagnosis, and management. 2019

Capurso, Gabriele / Traini, Mariaemilia / Piciucchi, Matteo / Signoretti, Marianna / Arcidiacono, Paolo Giorgio. ·Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Centre, San Raffaele Scientific Institute, Vita Salute San Raffaele University, Milan, Italy, capurso.gabriele@hsr.it. · Digestive and Liver Disease Unit, Sant'Andrea Hospital, Sapienza University, Rome, Italy. ·Clin Exp Gastroenterol · Pubmed #30962702.

ABSTRACT: Exocrine pancreatic insufficiency (EPI) is a condition caused by reduced or inappropriate secretion or activity of pancreatic juice and its digestive enzymes, pancreatic lipase in particular. EPI can result in clinical manifestation and biochemical alterations causing reduced quality of life and life-threating complications. EPI is common in pancreatic disorders, where it should be suspected and actively investigated, and in many extrapancreatic conditions. There are various tests available to diagnose EPI, with indirect, noninvasive ones, such as concentration of fecal elastase being more commonly employed. Administration of pancreatic enzymes replacement therapy remains the mainstay of EPI treatment. The present review article will discuss current evidence regarding the prevalence of EPI, the available tests to diagnose it and its treatment.

6 Review Statin use is associated to a reduced risk of pancreatic cancer: A meta-analysis. 2019

Archibugi, Livia / Arcidiacono, Paolo Giorgio / Capurso, Gabriele. ·Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milan, Italy. · Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milan, Italy. Electronic address: capurso.gabriele@hsr.it. ·Dig Liver Dis · Pubmed #30314951.

ABSTRACT: BACKGROUND: Previous studies investigating the association between statin use and pancreatic cancer (PDAC) risk for a possible chemopreventive effect gathered heterogeneous results. AIMS: To conduct a systematic review and meta-analysis to clarify this association. METHODS: Comprehensive literature search of articles published up to February 2018, including case-control (CC),cohort studies (C), randomized controlled trials (RCTs) assessing association between statin use and PDAC risk. Studies had to report odds ratio (OR)/relative risk (RR), estimates with 95% confidence interval (CI), or provide data for their calculation. Pooled ORs with 95%CIs were calculated using random effects model, publication bias through Begg and Mazumdar test and heterogeneity by I RESULTS: 27 studies(13 CC, 9C, 5 RCTs) for a total population of 11,975 PDAC/3,433,175 controls contributed to the analysis. The overall pooled result demonstrated a reduced PDAC risk among statin users (OR 0.70; 95% CI 0.60-0.82; p < 0.0001), compared to non-users. Sensitivity analyses suggested the risk reduction to be more important in CC studies, studies conducted in Asia and Europe, in males and atorvastatin users. No publication bias found. CONCLUSIONS: The present meta-analysis suggests that statin use is associated with an overall PDAC risk reduction of 30%. Further studies are needed to clarify the association.

7 Review Results of surveillance in individuals at high-risk of pancreatic cancer: A systematic review and meta-analysis. 2018

Signoretti, Marianna / Bruno, Marco J / Zerboni, Giulia / Poley, Jan-Werner / Delle Fave, Gianfranco / Capurso, Gabriele. ·Digestive and Liver Disease Unit, S. Andrea Hospital, Rome, Italy. · Department of Gastroenterology and Hepatology, Erasmus Medical Center, University Medical Center, Rotterdam, The Netherlands. ·United European Gastroenterol J · Pubmed #29881603.

ABSTRACT: Background: Data on surveillance for pancreatic ductal adenocarcinoma (PDAC) in high-risk individuals (HRIs) with "familial pancreatic cancer" (FPC) and specific syndromes are limited and heterogeneous. Objective: We conducted a systematic review and meta-analysis of PDAC surveillance studies in HRIs. Methods: Prevalence of solid/cystic pancreatic lesions and of lesions considered a successful target of surveillance (proven resectable PDAC and high-grade precursors) was pooled across studies. The rate of lesions diagnosed by endoscopic ultrasonography (EUS)/magnetic resonance imaging (MRI) and across different HRI groups was calculated. Results: Sixteen studies incorporating 1588 HRIs were included. The pooled prevalence of pancreatic solid and cystic lesions was 5.8% and 20.2%, respectively. The pooled prevalence of patients with lesions considered a successful target of surveillance was 3.3%, being similar to EUS or MRI and varying across subgroups, being 3% in FPC, 4% in hereditary pancreatitis, 5% in familial melanoma, 6.3% in hereditary breast/ovarian cancer, and 12.2% in Peutz-Jeghers syndrome. The pooled estimated rate of lesions considered a successful target of surveillance during follow-up was 5/1000 person-years. Conclusion: Surveillance programs identify successful target lesions in 3.3% of HRIs with a similar yield of EUS and MRI and an annual risk of 0.5%. A higher rate of target lesions was reported in HRIs with specific DNA mutations.

8 Review Meta-analysis of mortality in patients with high-risk intraductal papillary mucinous neoplasms under observation. 2018

Vanella, G / Crippa, S / Archibugi, L / Arcidiacono, P G / Delle Fave, G / Falconi, M / Capurso, G. ·Digestive and Liver Disease Unit, Sant'Andrea Hospital, Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy. · Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Centre, San Raffaele Scientific Institute, 'Vita-Salute' University, Milan, Italy. · Pancreato-Biliary Endoscopy Division and Endosonography Division, Pancreas Translational and Clinical Research Centre, San Raffaele Scientific Institute, Milan, Italy. ·Br J Surg · Pubmed #29405253.

ABSTRACT: BACKGROUND: Although consensus guidelines suggest that patients with high-risk intraductal papillary mucinous neoplasms (IPMNs) should have surgery, a non-operative strategy is often selected in patients who are poor surgical candidates. The aim was to determine the risk of disease-related death from IPMN in patients with worrisome features or high-risk stigmata who were kept under observation. METHODS: A PubMed literature search was undertaken of articles published from August 1992 to June 2016 (updated October 2017). The methodology was developed from PRISMA and MOOSE checklists. Incidence proportions and rates of overall and IPMN-related deaths were calculated, with subgroup analyses for main-duct/mixed-type and branch-duct IPMNs. Quality of the studies, publication bias and heterogeneity were explored. RESULTS: Six studies reported data on overall mortality and eight described disease-specific mortality for 556 patients during follow-up ranging from 24·9 to 60·0 months. Pooled rates of overall and IPMN-related mortality were 30·9 (95 per cent c.i. 19·6 to 45·1) and 11·6 (6·0 to 21·2) per cent respectively. The pooled incidence rate for overall mortality was substantially higher than that for IPMN-related mortality: 78 (95 per cent c.i. 44 to 111) and 23 (9 to 37) per 1000 patient-years respectively. The pooled incidence rate for disease-specific mortality was considerably lower for branch-duct than for main-duct or mixed-type IPMNs: 5 (0 to 10) and 32 (12 to 52) per 1000 patient-years respectively. CONCLUSION: In patients unfit for surgery, IPMN-related mortality among patients with worrisome features and high-risk stigmata is low, and the risk of death from other causes much higher.

9 Review Endoscopy-guided ablation of pancreatic lesions: Technical possibilities and clinical outlook. 2017

Signoretti, Marianna / Valente, Roberto / Repici, Alessandro / Delle Fave, Gianfranco / Capurso, Gabriele / Carrara, Silvia. ·Marianna Signoretti, Roberto Valente, Gianfranco Delle Fave, Gabriele Capurso, Digestive and Liver Disease Unit, S.Andrea Hospital, University Sapienza, 00199 Rome, Italy. ·World J Gastrointest Endosc · Pubmed #28250896.

ABSTRACT: Endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP)-guided ablation procedures are emerging as a minimally invasive therapeutic alternative to radiological and surgical treatments for locally advanced pancreatic cancer (LAPC), pancreatic neuroendocrine tumours (PNETs), and pancreatic cystic lesions (PCLs). The advantages of treatment under endoscopic control are the real-time imaging guidance and the possibility to reach a deep target like the pancreas. Currently, radiofrequency probes specifically designed for ERCP or EUS ablation are available as well as hybrid cryotherm probe combining radiofrequency with cryotechnology. To date, many reports and case series have confirmed the safety and feasibility of that kind of ablation technique in the pancreatic setting. Moreover, EUS-guided fine-needle injection is emerging as a method to deliver ablative and anti-tumoral agents inside the tumuor. Ethanol injection has been proposed mostly for the treatment of PCLs and for symptomatic functioning PNETs, and the use of gemcitabine and paclitaxel is also interesting in this setting. EUS-guided injection of chemical or biological agents including mixed lymphocyte culture, oncolytic viruses, and immature dendritic cells has been investigated for the treatment of LAPC. Data on the long-term efficacy of these approaches, and large prospective randomized studies are needed to confirm the real clinical benefits of these techniques for the management of pancreatic lesions.

10 Review Gut microbiota and pancreatic diseases. 2017

Signoretti, Marianna / Roggiolani, Roberta / Stornello, Caterina / Delle Fave, Gianfranco / Capurso, Gabriele. ·Digestive and Liver Disease Unit, S. Andrea Hospital, Sapienza University, Rome, Italy. · Digestive and Liver Disease Unit, S. Andrea Hospital, Sapienza University, Rome, Italy - gabriele.capurso@gmail.com. ·Minerva Gastroenterol Dietol · Pubmed #28240004.

ABSTRACT: Changes in diet, lifestyle, and exposure to environmental risk factors account for the increased incidence of pancreatic disorders, including acute and chronic pancreatitis, and pancreatic cancer. The role of the microbiota in the development of pancreatic disorders is increasingly acknowledged. The translocation of gut bacteria and endotoxins following gut barrier failure is a key event contributing to the severity of acute pancreatitis, while small intestine bacterial overgrowth is common in patients with chronic pancreatitis and further worsens their symptoms and malnutrition. Specific molecular mimicry link the microbiota and Helicobacter pylori with autoimmune pancreatitis. Changes in the oral microbiota typical of periodontitis seem to be associated with an increased risk of developing pancreatic cancer. The composition of the gut microbiota is also unbalanced in the presence of risk factors for pancreatic cancer, such as obesity, smoking and diabetes. Helicobacter pylori infection, atrophic body gastritis and related decreased gastric acid secretion also seem associated with the risk of pancreatic cancer, although this area needs further research. The link between dysbiosis, immune response and proinflammatory status is most likely the key for these associations. The present review article will discuss current available evidence on the role of gut microbiota in pancreatic disorders, highlighting potential areas for future research.

11 Review Risk of pancreatic malignancy and mortality in branch-duct IPMNs undergoing surveillance: A systematic review and meta-analysis. 2016

Crippa, Stefano / Capurso, Gabriele / Cammà, Calogero / Fave, Gianfranco Delle / Castillo, Carlos Fernández-Del / Falconi, Massimo. ·Division of Pancreatic Surgery, Vita-Salute University, San Raffaele Scientific Institute, Milan, Italy. · Digestive and Liver Disease Unit, S. Andrea Hospital, Faculty of Medicine and Psychology, Sapienza University of Rome, Italy. · Gastroenterology Unit, Internal Medicine Department, University of Palermo, Palermo, Italy. · Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, USA. · Division of Pancreatic Surgery, Vita-Salute University, San Raffaele Scientific Institute, Milan, Italy. Electronic address: falconi.massimo@hsr.it. ·Dig Liver Dis · Pubmed #26965783.

ABSTRACT: BACKGROUND: Safety of non-operative management for low-risk branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) is debated. AIM: To perform a systematic review/meta-analysis to determine their risk of developing pancreatic malignancy and of pancreatic malignancy-related deaths. METHODS: A MEDLINE search was performed and methodology was based on PRISMA statement. Incidence rates of overall pancreatic malignancy, malignant BD-IPMN, IPMN-distinct PDAC, and of pancreatic malignancy-related death rates were calculated by dividing the total number of events by the total number of person-years (pyrs) of follow-up. Heterogeneity was determined by I(2) statistic. RESULTS: 20 studies including 2177 patients were included. Mean follow-up ranged from 29.3 to 76.7 months. Overall, 82 patients (3.7%) developed a pancreatic malignancy with a pooled estimate rate of 0.007/pyrs (I(2)=32.8%). The pooled estimate rate of malignant IPMN was 0.004/pyrs (I(2)=40.8%), and the pooled estimate rate of distinct PDAC 0.002/pyrs (I(2)=0%). The rate of death due to pancreatic malignancy during follow-up was 0.9%, with an overall pooled estimate rate of death of 0.002/pyrs (I(2)=0%). CONCLUSION: Non-operative management of low-risk BD-IPMN is safe, with a very low risk of malignant transformation of IPMN and of distinct PDAC. The rate of pancreatic malignancy-related mortality is low, particularly when compared with the mortality of pancreatic surgery.

12 Review Molecular pathogenesis and targeted therapy of sporadic pancreatic neuroendocrine tumors. 2015

Capurso, Gabriele / Archibugi, Livia / Delle Fave, Gianfranco. ·Digestive and Liver Disease Unit, Faculty of Medicine and Psychology, Sapienza University of Rome at S. Andrea Hospital, Rome, Italy. ·J Hepatobiliary Pancreat Sci · Pubmed #25619712.

ABSTRACT: Over the past few years, knowledge regarding the molecular pathology of sporadic pancreatic neuroendocrine tumors (PNETs) has increased substantially, and a number of targeted agents have been tested in clinical trials in this tumor type. For some of these agents there is a strong biological rationale. Among them, the mammalian target of rapamycin inhibitor Everolimus and the antiangiogenic agent Sunitinib have both been approved for the treatment of PNETs. However, there is lack of knowledge regarding biomarkers able to predict their efficacy, and mechanisms of resistance. Other angiogenesis inhibitors, such as Pazopanib, inhibitors of Src, Hedgehog or of PI3K might all be useful in association or sequence with approved agents. On the other hand, the clinical significance, and potential for treatment of the most common mutations occurring in sporadic PNETs, in the MEN-1 gene and in ATRX and DAXX, remains uncertain. The present paper reviews the main molecular changes occurring in PNETs and how they might be linked with treatment options.

13 Review Diabetes, smoking, alcohol use, and family history of cancer as risk factors for pancreatic neuroendocrine tumors: a systematic review and meta-analysis. 2015

Haugvik, Sven-Petter / Hedenström, Per / Korsæth, Emilie / Valente, Roberto / Hayes, Alastair / Siuka, Darko / Maisonneuve, Patrick / Gladhaug, Ivar Prydz / Lindkvist, Björn / Capurso, Gabriele. ·Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Oslo, Norway. ·Neuroendocrinology · Pubmed #25613442.

ABSTRACT: BACKGROUND AND AIMS: Risk factors for pancreatic neuroendocrine tumors (PNETs) are not well understood. The aim of this systematic review was to assess if diabetes mellitus, smoking, alcohol use, and family history of cancer are risk factors for PNETs. METHODS: MEDLINE and abstracts from the European and North American Neuroendocrine Tumor Societies (ENETS and NANETS) were searched for studies published until October 2013. Eligible studies were selected according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RESULTS: Five studies evaluating 4 individual populations were included (study accrual period 2000-2011) into the meta-analysis, involving 827 cases (range 160-309 per study) and 2,407 controls (range 233-924 per study). All studies had a case-control design and described regional series. The pooled adjusted odds ratio was 2.74 (95% CI: 1.63-4.62; p < 0.01; I(2) = 60.4%) for history of diabetes, 1.21 (95% CI: 0.92-1.58; p = 0.18; I(2) = 45.8%) for ever smoking, 1.37 (95% CI: 0.99-1.91; p = 0.06; I(2) = 0.0%) for heavy smoking, 1.09 (95% CI: 0.64-1.85; p = 0.75; I(2) = 85.2%) for ever alcohol use, 2.72 (95% CI: 1.25-5.91; p = 0.01; I(2) = 57.8%) for heavy alcohol use, and 2.16 (95% CI: 1.64-2.85; p < 0.01; I(2) = 0.0%) for first-degree family history of cancer. CONCLUSIONS: Diabetes mellitus and first-degree family history of cancer are associated with an increased risk of sporadic PNET. There was also a trend for diagnosis of sporadic PNET associated with heavy smoking. Alcohol use may be a risk factor for PNET, but there was considerable heterogeneity in the meta-analysis. These results suggest the need for a larger, homogeneous, international study for the clarification of risk factors for the occurrence of PNET.

14 Review Diagnostic and therapeutic role of endoscopy in gastroenteropancreatic neuroendocrine neoplasms. 2014

Attili, Fabia / Capurso, Gabriele / Vanella, Giuseppe / Fuccio, Lorenzo / Delle Fave, Gianfranco / Costamagna, Guido / Larghi, Alberto. ·Digestive Endoscopy Unit, Catholic University, Rome, Italy. · Division of Digestive and Liver Disease, University La Sapienza, Rome, Italy. · Division of Gastroenterology, S. Orsola-Malpighi Hospital, University of Bologna, Italy. · Digestive Endoscopy Unit, Catholic University, Rome, Italy. Electronic address: albertolarghi@yahoo.it. ·Dig Liver Dis · Pubmed #23731843.

ABSTRACT: Gastroenteropancreatic neuroendocrine neoplasms have substantially increased over the last decades. Because of the indolent clinical course of the disease even in advance stages and the rise in the incidental diagnosis of small asymptomatic lesions, the prevalence of gastroenteropancreatic neuroendocrine neoplasms is higher than that of pancreatic, gastric and oesophageal adenocarcinomas, making them the second most prevalent cancer type of the gastrointestinal tract. This increase in the overall prevalence of gastroenteropancreatic neuroendocrine neoplasms has been paralleled by a growth in the importance of the endoscopist in the care of these patients, who usually require a multidisciplinary approach. In this manuscript the diagnostic and therapeutic role of endoscopic for gastroenteropancreatic neuroendocrine neoplasms will be reviewed.

15 Review Signalling pathways passing Src in pancreatic endocrine tumours: relevance for possible combined targeted therapies. 2013

Capurso, Gabriele / Di Florio, Alessia / Sette, Claudio / Delle Fave, Gianfranco. ·Digestive and Liver Disease Unit, II Medical School, University of Rome La Sapienza, Rome, Italy. ·Neuroendocrinology · Pubmed #22441103.

ABSTRACT: The most frequent molecular abnormalities in pancreatic endocrine tumours (PETs) are mutations of the MEN1 gene, deregulation of the PI3K/AKT/mTOR signalling pathway and overactivation of growth factors and their receptors, such as the VEGF. On this basis, everolimus (Afinitor®; Novartis) and sunitinib (Sutent®; Pfizer) have both been approved by the FDA for the treatment of progressive, unresectable, locally advanced or metastatic PETs. However, molecular or surrogate markers able to predict the response of PET patients to treatment with these drugs are not available, and cancer cells treated with targeted therapies might develop escape pathways that evoke pro-survival feedback responses. The existence of cross-talk between different molecular pathways in PETs has been poorly investigated. In the present review, we present data supporting an important role for Src family kinases (SFKs) in PETs, together with the recent observation of a novel role for SFK in modulating the mTOR pathway activity. Of note, while treatment with everolimus triggered the activation of a survival response dependent on PI3K/AKT signalling in vitro, the simultaneous inhibition of SFKs blocked the activation of this unwanted escape signal. These studies might set the ground for the investigation of combined treatment of PETs with SFK and mTOR inhibitors.

16 Review Novel molecular targets for the treatment of gastroenteropancreatic endocrine tumors: answers and unsolved problems. 2012

Capurso, Gabriele / Fendrich, Volker / Rinzivillo, Maria / Panzuto, Francesco / Bartsch, Detlef K / Delle Fave, Gianfranco. ·Digestive and Liver Disease Unit, S. Andrea Hospital, Faculty of Medicine and Psychology, Sapienza University of Rome at S. Andrea Hospital, Via di Grottarossa 1035, 00189 Rome, Italy. gianfranco.dellefave@uniroma1.it. ·Int J Mol Sci · Pubmed #23344019.

ABSTRACT: As more knowledge on molecular alterations favoring carcinogenesis and spreading of gastroenteropancreatic endocrine tumors has become available, a number of targeted agents interfering with key growth and angiogenic pathways have been explored in preclinical and clinical studies. The mTOR inhibitor Everolimus, and the multi-target antiangiogenetic agent Sunitinib, have been shown to be effective and thus have been approved by the FDA for treatment of pancreatic endocrine tumors. However, there is little data on the primary resistance to targeted agents on these tumors. The goals of the present review are to elucidate the possible advantage of combined treatments in overcoming induced resistances, and to identify biomarkers able to predict clinical efficacy. Moreover, the role of interesting targets for which a strong biological rationale exists, and specific inhibitors are available, such as the Src Family Kinases and the Hedgehog Pathway, are discussed. There is now need for more preclinical studies on cell lines and animal models to provide a stronger preclinical background in this field, as well as clinical trials specifically comparing one targeted therapy with another or combining different targeted agents.

17 Review Molecular pathology and genetics of pancreatic endocrine tumours. 2012

Capurso, Gabriele / Festa, Stefano / Valente, Roberto / Piciucchi, Matteo / Panzuto, Francesco / Jensen, Robert T / Delle Fave, Gianfranco. ·Digestive and Liver Disease Unit, Faculty of Medicine and Psychology, S. Andrea Hospital, Sapienza University of Rome, Via di Grottarossa 1035, 00189 Rome, Italy. ·J Mol Endocrinol · Pubmed #22586144.

ABSTRACT: Pancreatic neuroendocrine tumours (PETs) are the second most frequent pancreatic neoplasms. Their poor chemosensitivity, high rate of metastatic disease and relatively long survival make PETs an ideal field to be explored for novel therapies based on specific molecular changes. PETs are generally sporadic but can also arise within hereditary syndromes, such as multiple endocrine neoplasia type 1, von Hippel-Lindau, neurofibromatosis type 1 and tuberous sclerosis complex, which represent a model for sporadic cases too. Among allelic imbalances, main genomic changes involve gain of 17q, 7q and 20q and loss of 11q, 6q and 11p, which identify regions of putative candidate oncogenes or tumour suppressor genes (TSGs), respectively, sometime with potential prognostic significance. Overexpression of Src-like kinases and cyclin D1 (CCND1) oncogene has been described. As for TSGs, P53 (TP53), DPC4/SMAD4 and RB (RB1) are not implicated in PET tumorigenesis, while for p16INK4a (CDKN2A), TIMP3, RASSF1A and hMLH1, more data are available, suggesting a role for methylation as a silencing mechanism. In the last decade, gene expression profile studies, analysis of microRNAs and, more recently, large-scale mutational analysis have highlighted commonly altered molecular pathways in the pathology of PETs. The roles of the mammalian target of rapamycin pathway, and its connection with Src kinases, and the activity of a number of tyrosine kinase receptors seem to be pivotal, as confirmed by the results of recent clinical trials with targeted agents. Mutations of DAXX and ATRX are common and related to altered telomeres but not to prognosis.

18 Review Role of resection of the primary pancreatic neuroendocrine tumour only in patients with unresectable metastatic liver disease: a systematic review. 2011

Capurso, Gabriele / Bettini, Rossella / Rinzivillo, Maria / Boninsegna, Letizia / Delle Fave, Gianfranco / Falconi, Massimo. ·Digestive and Liver Disease Unit, II School of Medicine, 'Sapienza' University of Rome, Rome, Italy. ·Neuroendocrinology · Pubmed #21358176.

ABSTRACT: BACKGROUND: Surgery remains the only curative option for pancreatic neuroendocrine tumours (PNETs), but its indication is limited by metastatic disease in most patients. Indication for removing the primary lesion only in the setting of unresectable liver disease is controversial. The present systematic review aims at determining the potential bene- fits (survival, progression-free survival) or harms (morbidity, mortality) of surgical resection of the primary lesion only in patients with PNETs and unresectable metastases. METHODS: Medline was queried for studies reporting the outcome of PNET patients with unresectable liver metastases whenever there was an explicit comparison between resection of the primary lesion only ('active treatment') and no resection ('non-active treatment'). The primary outcome was survival; possible secondary outcomes were progression-free survival, treatment-related mortality and morbidity, and relief of symptoms. RESULTS: Only 3 cohort studies found were eligible and analysed; no meta-analysis could be performed. The number of patients undergoing 'active treatment' varied from 16 to 20, with a percentage ranging from 17 to 39% of cohorts. Survival was longer in patients who received 'active treatment' in 2 studies, and the 5-year survival rate also seemed higher, without significant complications. DISCUSSION: Available data suggest a possible benefit of resection of the primary lesion only in this setting. However, a bias towards a more aggressive surgical approach in patients with a better performance status or less advanced disease seems likely, and no conclusion can be drawn except for the need of randomised trials. We calculated that such a trial would require at least 118 patients per arm.

19 Clinical Trial Ki-67 grading of nonfunctioning pancreatic neuroendocrine tumors on histologic samples obtained by EUS-guided fine-needle tissue acquisition: a prospective study. 2012

Larghi, Alberto / Capurso, Gabriele / Carnuccio, Antonella / Ricci, Riccardo / Alfieri, Sergio / Galasso, Domenico / Lugli, Francesca / Bianchi, Antonio / Panzuto, Francesco / De Marinis, Laura / Falconi, Massimo / Delle Fave, Gianfranco / Doglietto, Giovanni Battista / Costamagna, Guido / Rindi, Guido. ·Digestive Endoscopy Unit, Divisionof Digestive and Liver Disease, Catholic University, Rome, Italy. albertolarghi@yahoo.it ·Gastrointest Endosc · Pubmed #22898415.

ABSTRACT: BACKGROUND: Preoperative determination of Ki-67 expression, an important prognostic factor for grading nonfunctioning pancreatic endocrine tumors (NF-PETs), remains an important clinical challenge. OBJECTIVE: To prospectively evaluate the feasibility, yield, and clinical impact of EUS-guided fine-needle tissue acquisition (EUS-FNTA) with a large-gauge needle to obtain tissue samples for histologic diagnosis and Ki-67 analysis in patients with suspected NF-PETs. DESIGN: Prospective cohort study. SETTING: Tertiary-care academic medical center. PATIENTS: Consecutive patients with a single pancreatic lesion suspicious for NF-PET on imaging. INTERVENTION: EUS-FNTA with a 19-gauge needle. MAIN OUTCOME MEASUREMENTS: Feasibility and yield of EUS-FNTA for diagnosis and Ki-67 expression determination. RESULTS: Thirty patients (mean [± SD] age 55.7 ± 14.9 years), with a mean (± SD) lesion size of 16.9 ± 6.1 mm were enrolled. EUS-FNTA was successfully performed without complications in all patients, with a mean (± SD) of 2.7 ± 0.5 passes per patient. Adequate samples for histologic examination were obtained in 28 of the 30 patients (93.3%). Ki-67 determination could be performed in 26 of these 28 patients (92.9%, 86.6% overall), 12 of whom underwent surgical resection. Preoperative and postoperative Ki-67 proliferation indexes were concordant in 10 patients (83.3%), whereas 2 patients were upstaged from G1 to G2 or downstaged from G2 to G1, respectively. LIMITATIONS: Single center study with a single operator. CONCLUSION: In patients with suspected nonfunctioning low-grade to intermediate-grade pancreatic neuroendocrine tumors (p-NETs), retrieval of tissue specimens with EUS-FNTA by using a 19-gauge needle is safe, feasible, and highly accurate for both diagnosis and Ki-67 determination. A Ki-67 proliferative index acquired through this technique might be of great help for further therapeutic decisions.

20 Article Germline BRCA2 K3326X and CHEK2 I157T mutations increase risk for sporadic pancreatic ductal adenocarcinoma. 2019

Obazee, O / Archibugi, L / Andriulli, A / Soucek, P / Małecka-Panas, E / Ivanauskas, A / Johnson, T / Gazouli, M / Pausch, T / Lawlor, R T / Cavestro, G M / Milanetto, A C / Di Leo, M / Pasquali, C / Hegyi, P / Szentesi, A / Radu, C E / Gheorghe, C / Theodoropoulos, G E / Bergmann, F / Brenner, H / Vodickova, L / Katzke, V / Campa, D / Strobel, O / Kaiser, J / Pezzilli, R / Federici, F / Mohelnikova-Duchonova, B / Boggi, U / Lemstrova, R / Johansen, J S / Bojesen, S E / Chen, I / Jensen, B V / Capurso, G / Pazienza, V / Dervenis, C / Sperti, C / Mambrini, A / Hackert, T / Kaaks, R / Basso, D / Talar-Wojnarowska, R / Maiello, E / Izbicki, J R / Cuk, K / Saum, K U / Cantore, M / Kupcinskas, J / Palmieri, O / Delle Fave, G / Landi, S / Salvia, R / Fogar, P / Vashist, Y K / Scarpa, A / Vodicka, P / Tjaden, C / Iskierka-Jazdzewska, E / Canzian, F. ·Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Digestive and Liver Disease Unit, Pancreatic Disorders Clinic, S. Andrea Hospital, University of Sapienza, Rome, Italy. · Pancreatico/Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy. · Division of Gastroenterology and Research Laboratory, Department of Oncology, IRCCS Scientific Institute and Regional General Hospital "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy. · Laboratory of Pharmacogenomics, Biomedical Centre, Faculty of Medicine in Plzen, Charles University in Prague, Plzen, Czech Republic. · Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland. · Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania. · Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Department of Basic Medical Sciences, Laboratory of Biology, Medical School National and Kapodistrian University of Athens, Athens, Greece. · Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Heidelberg, Germany. · ARC-Net, Applied Research on Cancer Centre, University of Verona, Verona, Italy. · Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy. · Department of Surgery, Oncology and Gastroenterology -DiSCOG, University of Padova, Padova, Italy. · Institute for Translational Medicine and 1st Department of Medicine, University of Pécs, Pécs, Hungary. · Fundeni Clinical Institute, Bucharest, Romania. · First Propaedeutic Surgical Department, "Hippocratio" General Hospital Athens Medical School, National and Kapodistrian University of Athens, Athens, Greece. · Pathologisches Institut der Universität Heidelberg, Heidelberg, Germany. · Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany. · German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. · Institute of Biology and Medical Genetics, 1st Medical Faculty, Charles University, Prague and Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Prague, Czech Republic. · Dipartimento di Biologia, Università di Pisa, Pisa, Italy. · Pancreas Unit, Department of Digestive System, Sant'Orsola-Malpighi Hospital, Bologna, Italy. · Department of Massa Carrara Oncological, Azienda USL Toscana Nord Ovest, Carrara, Italy. · Department of Oncology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic. · Division of General and Transplant Surgery, Pisa University Hospital, Pisa, Italy. · Department of Oncology, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark. · Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark. · Department of Surgery, Konstantopouleion General Hospital of Athens, Athens, Greece. · Department of Laboratory Medicine, University-Hospital of Padova, Padova, Italy. · Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. · Department of Surgery, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy. · Section for Visceral Surgery, Department of Surgery, Kantonsspital Aarau AG, Aarau, Switzerland. · Institute of Experimental Medicine, Czech Academy of Science, Prague and Institute of Biology and Medical Genetics, 1st Medical Faculty, Charles University, Prague, Czech Republic. · Department of Hematology, Medical University of Lodz, Lodz, Poland. ·Int J Cancer · Pubmed #30672594.

ABSTRACT: Rare truncating BRCA2 K3326X (rs11571833) and pathogenic CHEK2 I157T (rs17879961) variants have previously been implicated in familial pancreatic ductal adenocarcinoma (PDAC), but not in sporadic cases. The effect of both mutations in important DNA repair genes on sporadic PDAC risk may shed light on the genetic architecture of this disease. Both mutations were genotyped in germline DNA from 2,935 sporadic PDAC cases and 5,626 control subjects within the PANcreatic Disease ReseArch (PANDoRA) consortium. Risk estimates were evaluated using multivariate unconditional logistic regression with adjustment for possible confounders such as sex, age and country of origin. Statistical analyses were two-sided with p values <0.05 considered significant. K3326X and I157T were associated with increased risk of developing sporadic PDAC (odds ratio (OR

21 Article Results of First-Round of Surveillance in Individuals at High-Risk of Pancreatic Cancer from the AISP (Italian Association for the Study of the Pancreas) Registry. 2019

Paiella, Salvatore / Capurso, Gabriele / Cavestro, Giulia Martina / Butturini, Giovanni / Pezzilli, Raffaele / Salvia, Roberto / Signoretti, Marianna / Crippa, Stefano / Carrara, Silvia / Frigerio, Isabella / Bassi, Claudio / Falconi, Massimo / Iannicelli, Elsa / Giardino, Alessandro / Mannucci, Alessandro / Laghi, Andrea / Laghi, Luigi / Frulloni, Luca / Zerbi, Alessandro. ·General and Pancreatic Surgery Department, Pancreas Institute, University of Verona, Verona, Italy. · Digestive and Liver Disease Unit, S. Andrea Hospital, University Sapienza, Rome, Italy. · Gastroenterology and Gastrointestinal Endoscopy Unit, IRCCS Ospedale San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy. · Pancreatic Surgery Unit, Casa di Cura Pederzoli Hospital, Peschiera del Garda, Italy. · Internal Medicine, University of Bologna, Bologna, Italy. · Pancreatic Surgery Unit, IRCCS Ospedale San Raffaele Scientific Institute, Vita Salute San Raffaele University, Milano, Italy. · Gastrointestinal Endoscopy, Istituto Clinico Humanitas, Milano, Italy. · Radiology Unit, S. Andrea Hospital, University Sapienza, Rome, Italy. · Hereditary Cancer Genetics Clinic, Humanitas Clinical and Research Center, Milano, Italy. · Gastroenterology B Unit, Pancreas Institute, University of Verona, Verona, Italy. · Pancreatic Surgery Unit, Humanitas Clinical and Research Center, Milano, Italy. ·Am J Gastroenterol · Pubmed #30538291.

ABSTRACT: INTRODUCTION: Surveillance programs on high-risk individuals (HRIs) can detect pre-malignant lesions or early pancreatic cancer (PC). We report the results of the first screening round of the Italian multicenter program supported by the Italian Association for the study of the Pancreas (AISP). METHODS: The multicenter surveillance program included asymptomatic HRIs with familial (FPC) or genetic frailty (GS: BRCA1/2, p16/CDKN2A, STK11/LKB1or PRSS1, mutated genes) predisposition to PC. The surveillance program included at least an annual magnetic resonance cholangio pancreatography (MRCP). Endoscopic ultrasound (EUS) was proposed to patients who refused or could not be submitted to MRCP. RESULTS: One-hundreds eighty-seven HRIs underwent a first-round screening examination with MRCP (174; 93.1%) or EUS (13; 6.9%) from September 2015 to March 2018.The mean age was 51 years (range 21-80).One-hundreds sixty-five (88.2%) FPC and 22 (11.8%) GF HRIs were included. MRCP detected 28 (14.9%) presumed branch-duct intraductal papillary mucinous neoplasms (IPMN), 1 invasive carcinoma/IPMN and one low-grade mixed-type IPMN, respectively. EUS detected 4 PC (2.1%): 1 was resected, 1 was found locally advanced intraoperatively, and 2 were metastatic. Age > 50 (OR 3.3, 95%CI 1.4-8), smoking habit (OR 2.8, 95%CI 1.1-7.5), and having > 2 relatives with PC (OR 2.7, 95%CI 1.1-6.4) were independently associated with detection of pre-malignant and malignant lesions. The diagnostic yield for MRCP/EUS was 24% for cystic lesions. The overall rate of surgery was 2.6% with nil mortality. DISCUSSION: The rate of malignancies found in this cohort was high (2.6%). According to the International Cancer of the Pancreas Screening Consortium the screening goal achievement was high (1%).

22 Article Impact of intensified chemotherapy in metastatic pancreatic ductal adenocarcinoma (PDAC) in clinical routine in Europe. 2019

Javed, Muhammad Ahsan / Beyer, Georg / Le, Nha / Vinci, Alessio / Wong, Helen / Palmer, Daniel / Morgan, Robert D / Lamarca, Angela / Hubner, Richard A / Valle, Juan W / Alam, Salma / Chowdhury, Sumsur / Ma, Yuk Ting / Archibugi, Livia / Capurso, Gabriele / Maisonneuve, Patrick / Neesse, Albrecht / Sund, Malin / Schober, Marvin / Krug, Sebastian. ·NIHR Liverpool Pancreas Biomedical Research Unit, Institute of Translational Medicine, Royal Liverpool University Hospital, United Kingdom. · Department of Medicine A, University Medicine Greifswald, Greifswald, Germany; Medical Department II, University Hospital, LMU, Munich, Germany. · Gastroenterology Division, Second Internal Medicine Department, Semmelweis University, Budapest, Hungary. · University of Pavia, Department of Surgery, S. Matteo University Hospital Foundation, Pavia, Italy. · Department of Quality and Information Intelligence, The Clatterbridge Cancer Centre NHS Foundation Trust, Wirral, United Kingdom. · Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, United Kingdom. · Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom. · Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom; Institute of Cancer Sciences, University of Manchester, Manchester, United Kingdom. · Department of Hepatobiliary Oncology, New Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom. · Digestive and Liver Disease Unit, S. Andrea Hospital, University Sapienza, Rome, Italy. · Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy. · University Medical Centre Göttingen, Department of Gastroenterology and Gastrointestinal Oncology, Göttingen, Germany. · University of Umea, Department of Surgical and Perioperative Sciences, Umea, Sweden. Electronic address: malin.sund@surgery.umu.se. · Department of Gastroenterology and Hepatology, Martin-Luther-University Halle-Wittenberg, Halle, Germany. ·Pancreatology · Pubmed #30529068.

ABSTRACT: BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis. Gemcitabine is the standard chemotherapy for patients with metastatic pancreatic adenocarcinoma (MPA). Randomized clinical trials evaluating intensified chemotherapies including FOLFIRINOX and nab-paclitaxel plus gemcitabine (NAB+GEM) have shown improvement in survival. Here, we have evaluated the efficacy of intensified chemotherapy versus gemcitabine monotherapy in real-life settings across Europe. METHODS: A retrospective multi-center study including 1056 MPA patients, between 2012 and 2015, from nine centers in UK, Germany, Italy, Hungary and the Swedish registry was performed. Follow-up was at least 12 months. Cox proportional Harzards regression was used for uni- and multivariable evaluation of prognostic factors. RESULTS: Of 1056 MPA patients, 1030 (98.7%) were assessable for survival analysis. Gemcitabine monotherapy was the most commonly used regimen (41.3%), compared to FOLFIRINOX (n = 204, 19.3%), NAB+GEM (n = 81, 7.7%) and other gemcitabine- or 5-FU-based regimens (n = 335, 31.7%). The median overall survival (OS) was: FOLFIRINOX 9.9 months (95%CI 8.4-12.6), NAB+GEM 7.9 months (95%CI 6.2-10.0), other combinations 8.5 months (95%CI 7.7-9.3) and gemcitabine monotherapy 4.9 months (95%CI 4.4-5.6). Compared to gemcitabine monotherapy, any combination of chemotherapeutics improved the survival with no significant difference between the intensified regimens. Multivariable analysis showed an association between treatment center, male gender, inoperability at diagnosis and performance status (ECOG 1-3) with poor prognosis. CONCLUSION: Gemcitabine monotherapy was predominantly used in 2012-2015. Intensified chemotherapy improved OS in comparison to gemcitabine monotherapy. In real-life settings, the OS rates of different treatment approaches are lower than shown in randomized phase III trials.

23 Article Genetic determinants of telomere length and risk of pancreatic cancer: A PANDoRA study. 2019

Campa, Daniele / Matarazzi, Martina / Greenhalf, William / Bijlsma, Maarten / Saum, Kai-Uwe / Pasquali, Claudio / van Laarhoven, Hanneke / Szentesi, Andrea / Federici, Francesca / Vodicka, Pavel / Funel, Niccola / Pezzilli, Raffaele / Bueno-de-Mesquita, H Bas / Vodickova, Ludmila / Basso, Daniela / Obazee, Ofure / Hackert, Thilo / Soucek, Pavel / Cuk, Katarina / Kaiser, Jörg / Sperti, Cosimo / Lovecek, Martin / Capurso, Gabriele / Mohelnikova-Duchonova, Beatrice / Khaw, Kay-Tee / König, Anna-Katharina / Kupcinskas, Juozas / Kaaks, Rudolf / Bambi, Franco / Archibugi, Livia / Mambrini, Andrea / Cavestro, Giulia Martina / Landi, Stefano / Hegyi, Péter / Izbicki, Jakob R / Gioffreda, Domenica / Zambon, Carlo Federico / Tavano, Francesca / Talar-Wojnarowska, Renata / Jamroziak, Krzysztof / Key, Timothy J / Fave, Gianfranco Delle / Strobel, Oliver / Jonaitis, Laimas / Andriulli, Angelo / Lawlor, Rita T / Pirozzi, Felice / Katzke, Verena / Valsuani, Chiara / Vashist, Yogesh K / Brenner, Hermann / Canzian, Federico. ·Department of Biology, University of Pisa, Pisa, Italy. · Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Institute for Health Research Liverpool Pancreas Biomedical Research Unit, University of Liverpool, Liverpool, United Kingdom. · Medical Oncology, Academic Medical Centre, Amsterdam, The Netherlands. · Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Pancreatic and Digestive Endocrine Surgery - Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padova, Padova, Italy. · Institute for Translational Medicine, University of Pécs, Pécs, Hungary. · First Department of Medicine, University of Szeged, Szeged, Hungary. · Oncological Department, Azienda USL Toscana Nord Ovest, Oncological Unit of Massa Carrara, Carrara, Italy. · Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Science of Czech Republic, Prague, Czech Republic. · Institute of Biology and Medical Genetics, 1st Medical Faculty, Charles University, Prague, Czech Republic. · Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic. · Department of Surgery, Unit of Experimental Surgical Pathology, University of Pisa, Pisa, Italy. · Pancreas Unit, Department of Digestive System, Sant'Orsola-Malpighi Hospital, Bologna, Italy. · Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. · Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands. · Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, United Kingdom. · Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. · Department of Laboratory Medicine, University-Hospital of Padova, Padua, Italy. · Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany. · Third Surgical Clinic - Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padova, Padova, Italy. · Department of Surgery I, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic. · Digestive and Liver Disease Unit, S. Andrea Hospital, 'Sapienza' University, Rome, Italy. · PancreatoBiliary Endoscopy and EUS Division, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Vita Salute San Raffaele University, Milan, Italy. · Department of Oncology, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic. · University of Cambridge School of Clinical Medicine Clinical Gerontology Unit, Addenbrooke's Hospital, Cambridge, United Kingdom. · Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania. · Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Blood Transfusion Service, Azienda Ospedaliero-Universitaria Meyer, Florence, Italy. · Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan, Italy. · MTA-SZTE Momentum Translational Gastroenterology Research Group, Szeged, Hungary. · Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. · Division of Gastroenterology and Molecular Biology Lab, IRCCS Ospedale Casa Sollievo Sofferenza, San Giovanni Rotondo, Italy. · Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland. · Institute of Hematology and Transfusion Medicine, Warsaw, Poland. · Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom. · ARC-NET, University and Hospital Trust of Verona, Verona, Italy. · Division of Abdominal Surgery, IRCCS Ospedale Casa Sollievo Sofferenza, San Giovanni Rotondo, Italy. · Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany. · German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. ·Int J Cancer · Pubmed #30325019.

ABSTRACT: Telomere deregulation is a hallmark of cancer. Telomere length measured in lymphocytes (LTL) has been shown to be a risk marker for several cancers. For pancreatic ductal adenocarcinoma (PDAC) consensus is lacking whether risk is associated with long or short telomeres. Mendelian randomization approaches have shown that a score built from SNPs associated with LTL could be used as a robust risk marker. We explored this approach in a large scale study within the PANcreatic Disease ReseArch (PANDoRA) consortium. We analyzed 10 SNPs (ZNF676-rs409627, TERT-rs2736100, CTC1-rs3027234, DHX35-rs6028466, PXK-rs6772228, NAF1-rs7675998, ZNF208-rs8105767, OBFC1-rs9420907, ACYP2-rs11125529 and TERC-rs10936599) alone and combined in a LTL genetic score ("teloscore", which explains 2.2% of the telomere variability) in relation to PDAC risk in 2,374 cases and 4,326 controls. We identified several associations with PDAC risk, among which the strongest were with the TERT-rs2736100 SNP (OR = 1.54; 95%CI 1.35-1.76; p = 1.54 × 10

24 Article Long-term follow-up of low-risk branch-duct IPMNs of the pancreas: is main pancreatic duct dilatation the most worrisome feature? 2018

Petrone, Maria Chiara / Magnoni, Pietro / Pergolini, Ilaria / Capurso, Gabriele / Traini, Mariaemilia / Doglioni, Claudio / Mariani, Alberto / Crippa, Stefano / Arcidiacono, Paolo Giorgio. ·Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Center, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy. petrone.mariachiara@hsr.it. · Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Center, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy. · Department of Surgery, Università Politecnica delle Marche, Ancona, Italy. · Digestive and Liver Disease Unit, S. Andrea University Hospital, Rome, Italy. · Department of Pathology, IRCCS San Raffaele Scientific Institute, Milan, Italy. · Pancreas Translational & Clinical Research Center, Division of Pancreatic Surgery, Università Vita-Salute, IRCCS San Raffaele Scientific Institute, Milan, Italy. ·Clin Transl Gastroenterol · Pubmed #29895904.

ABSTRACT: OBJECTIVES: The management of branch-duct IPMN remains controversial due to the relatively low rate of malignant degeneration and the uncertain predictive role of high-risk stigmata (HRS) and worrisome features (WFs) identified by the 2012 International Consensus Guidelines. Our aim was to evaluate the evolution of originally low-risk (Fukuoka-negative) BD-IPMNs during a long follow-up period in order to determine whether the appearance of any clinical or morphological variables may be independently associated with the development of malignancy over time. METHODS: A prospectively collected database of all patients with BD-IPMN referring to our Institute between 2002 and 2016 was retrospectively analyzed. Univariate and multivariate analysis of association between changes during follow-up, including appearance of HRS/WFs, and development of malignancy (high-grade dysplasia/invasive carcinoma) was performed. RESULTS: A total of 167 patients were selected for analysis, and seven developed malignant disease (4.2%). During a median follow-up time of 55 months, HRS appeared in only three cases but predicted malignancy with 100% specificity. Worrisome features, on the other hand, appeared in 44 patients (26.3%). Appearance of mural nodules and MPD dilatation >5 mm showed a significant association with malignancy in multivariate analysis (p = 0.004 and p = 0.001, respectively). MPD dilatation in particular proved to be the strongest independent risk factor for development of malignancy (OR = 24.5). CONCLUSIONS: The risk of pancreatic malignancy in this population is low but definite. The presence of major WFs, and especially MPD dilatation, should prompt a tighter follow-up with EUS and a valid cytological analysis whenever feasible.

25 Article Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer. 2018

Klein, Alison P / Wolpin, Brian M / Risch, Harvey A / Stolzenberg-Solomon, Rachael Z / Mocci, Evelina / Zhang, Mingfeng / Canzian, Federico / Childs, Erica J / Hoskins, Jason W / Jermusyk, Ashley / Zhong, Jun / Chen, Fei / Albanes, Demetrius / Andreotti, Gabriella / Arslan, Alan A / Babic, Ana / Bamlet, William R / Beane-Freeman, Laura / Berndt, Sonja I / Blackford, Amanda / Borges, Michael / Borgida, Ayelet / Bracci, Paige M / Brais, Lauren / Brennan, Paul / Brenner, Hermann / Bueno-de-Mesquita, Bas / Buring, Julie / Campa, Daniele / Capurso, Gabriele / Cavestro, Giulia Martina / Chaffee, Kari G / Chung, Charles C / Cleary, Sean / Cotterchio, Michelle / Dijk, Frederike / Duell, Eric J / Foretova, Lenka / Fuchs, Charles / Funel, Niccola / Gallinger, Steven / M Gaziano, J Michael / Gazouli, Maria / Giles, Graham G / Giovannucci, Edward / Goggins, Michael / Goodman, Gary E / Goodman, Phyllis J / Hackert, Thilo / Haiman, Christopher / Hartge, Patricia / Hasan, Manal / Hegyi, Peter / Helzlsouer, Kathy J / Herman, Joseph / Holcatova, Ivana / Holly, Elizabeth A / Hoover, Robert / Hung, Rayjean J / Jacobs, Eric J / Jamroziak, Krzysztof / Janout, Vladimir / Kaaks, Rudolf / Khaw, Kay-Tee / Klein, Eric A / Kogevinas, Manolis / Kooperberg, Charles / Kulke, Matthew H / Kupcinskas, Juozas / Kurtz, Robert J / Laheru, Daniel / Landi, Stefano / Lawlor, Rita T / Lee, I-Min / LeMarchand, Loic / Lu, Lingeng / Malats, Núria / Mambrini, Andrea / Mannisto, Satu / Milne, Roger L / Mohelníková-Duchoňová, Beatrice / Neale, Rachel E / Neoptolemos, John P / Oberg, Ann L / Olson, Sara H / Orlow, Irene / Pasquali, Claudio / Patel, Alpa V / Peters, Ulrike / Pezzilli, Raffaele / Porta, Miquel / Real, Francisco X / Rothman, Nathaniel / Scelo, Ghislaine / Sesso, Howard D / Severi, Gianluca / Shu, Xiao-Ou / Silverman, Debra / Smith, Jill P / Soucek, Pavel / Sund, Malin / Talar-Wojnarowska, Renata / Tavano, Francesca / Thornquist, Mark D / Tobias, Geoffrey S / Van Den Eeden, Stephen K / Vashist, Yogesh / Visvanathan, Kala / Vodicka, Pavel / Wactawski-Wende, Jean / Wang, Zhaoming / Wentzensen, Nicolas / White, Emily / Yu, Herbert / Yu, Kai / Zeleniuch-Jacquotte, Anne / Zheng, Wei / Kraft, Peter / Li, Donghui / Chanock, Stephen / Obazee, Ofure / Petersen, Gloria M / Amundadottir, Laufey T. ·Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, 21231, USA. aklein1@jhmi.edu. · Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, MD, 21287, USA. aklein1@jhmi.edu. · Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA. · Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, 06520, USA. · Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. · Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, 21231, USA. · Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. · Genomic Epidemiology Group, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany. · Department of Obstetrics and Gynecology, New York University School of Medicine, New York, NY, 10016, USA. · Department of Population Health, New York University School of Medicine, New York, NY, 10016, USA. · Department of Environmental Medicine, New York University School of Medicine, New York, NY, 10016, USA. · Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, 55905, USA. · Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, MD, 21287, USA. · Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, M5G 1×5, Canada. · Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, 94158, USA. · International Agency for Research on Cancer (IARC), 69372, Lyon, France. · Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany. · Division of Preventive Oncology, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany. · National Center for Tumor Diseases (NCT), 69120, Heidelberg, Germany. · Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), 3720 BA, Bilthoven, The Netherlands. · Department of Gastroenterology and Hepatology, University Medical Centre, 3584 CX, Utrecht, The Netherlands. · Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, SW7 2AZ, UK. · Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia. · Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, 02215, USA. · Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA. · Department of Biology, University of Pisa, 56126, Pisa, Italy. · Digestive and Liver Disease Unit, 'Sapienza' University of Rome, 00185, Rome, Italy. · Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy. · Cancer Genomics Research Laboratory, National Cancer Institute, Division of Cancer Epidemiology and Genetics, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, USA. · Cancer Care Ontario, University of Toronto, Toronto, Ontario, M5G 2L7, Canada. · Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, M5T 3M7, Canada. · Department of Pathology, Academic Medical Center, University of Amsterdam, 1007 MB, Amsterdam, The Netherlands. · Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Bellvitge Biomedical Research Institute (IDIBELL), Catalan Institute of Oncology (ICO), Barcelona, 08908, Spain. · Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, 65653, Brno, Czech Republic. · Yale Cancer Center, New Haven, CT, 06510, USA. · Department of Translational Research and The New Technologies in Medicine and Surgery, University of Pisa, 56126, Pisa, Italy. · Division of Aging, Brigham and Women's Hospital, Boston, MA, 02115, USA. · Boston VA Healthcare System, Boston, MA, 02132, USA. · Department of Basic Medical Sciences, Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, 106 79, Athens, Greece. · Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, VIC, 3004, Australia. · Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC, 3010, Australia. · Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, 3004, Australia. · Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA. · SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA. · Department of General Surgery, University Hospital Heidelberg, 69120, Heidelberg, Germany. · Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90032, USA. · Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, TX, 77230, USA. · First Department of Medicine, University of Szeged, 6725, Szeged, Hungary. · Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. · Department of Radiation Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, 21231, USA. · Institute of Public Health and Preventive Medicine, Charles University, 2nd Faculty of Medicine, 150 06, Prague 5, Czech Republic. · Epidemiology Research Program, American Cancer Society, Atlanta, GA, 30303, USA. · Department of Hematology, Institute of Hematology and Transfusion Medicine, 02-776, Warsaw, Poland. · Department of Epidemiology and Public Health, Faculty of Medicine, University of Ostrava, 701 03, Ostrava, Czech Republic. · Faculty of Medicine, University of Olomouc, 771 47, Olomouc, Czech Republic. · Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany. · School of Clinical Medicine, University of Cambridge, Cambridge, CB2 0SP, UK. · Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, 44195, USA. · ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), 08003, Barcelona, Spain. · CIBER Epidemiología y Salud Pública (CIBERESP), 08003, Barcelona, Spain. · Hospital del Mar Institute of Medical Research (IMIM), Universitat Autònoma de Barcelona, 08003, Barcelona, Spain. · Universitat Pompeu Fabra (UPF), 08002, Barcelona, Spain. · Department of Gastroenterology, Lithuanian University of Health Sciences, 44307, Kaunas, Lithuania. · Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. · ARC-NET: Centre for Applied Research on Cancer, University and Hospital Trust of Verona, 37134, Verona, Italy. · Department of Epidemiology, Harvard School of Public Health, Boston, MA, 02115, USA. · Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, 96813, USA. · Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center (CNIO), 28029, Madrid, Spain. · CIBERONC, 28029, Madrid, Spain. · Oncology Department, ASL1 Massa Carrara, Carrara, 54033, Italy. · Department of Public Health Solutions, National Institute for Health and Welfare, 00271, Helsinki, Finland. · Department of Oncology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital, 775 20, Olomouc, Czech Republic. · Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, 4029, Australia. · Department of General Surgery, University of Heidelburg, Heidelberg, Germany. · Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. · Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padua, 35124, Padua, Italy. · Pancreas Unit, Department of Digestive Diseases and Internal Medicine, Sant'Orsola-Malpighi Hospital, 40138, Bologna, Italy. · Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre-CNIO, 28029, Madrid, Spain. · Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, 08002, Barcelona, Spain. · Centre de Recherche en Épidémiologie et Santé des Populations (CESP, Inserm U1018), Facultés de Medicine, Université Paris-Saclay, UPS, UVSQ, Gustave Roussy, 94800, Villejuif, France. · Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA. · Department of Medicine, Georgetown University, Washington, 20057, USA. · Laboratory for Pharmacogenomics, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, 323 00, Pilsen, Czech Republic. · Department of Surgical and Perioperative Sciences, Umeå University, 901 85, Umeå, Sweden. · Department of Digestive Tract Diseases, Medical University of Łodz, 90-647, Łodz, Poland. · Division of Gastroenterology and Research Laboratory, IRCCS Scientific Institute and Regional General Hospital "Casa Sollievo della Sofferenza", 71013, San Giovanni Rotondo, FG, Italy. · Division of Research, Kaiser Permanente Northern California, Oakland, CA, 94612, USA. · Department of General, Visceral and Thoracic Surgery, University Hamburg-Eppendorf, 20246, Hamburg, Germany. · Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA. · Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, 142 20, Prague 4, Czech Republic. · Department of Epidemiology and Environmental Health, University at Buffalo, Buffalo, NY, 14214, USA. · Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA. · Department of Epidemiology, University of Washington, Seattle, WA, 98195, USA. · Perlmutter Cancer Center, New York University School of Medicine, New York, NY, 10016, USA. · Department of Biostatistics, Harvard School of Public Health, Boston, MA, 02115, USA. · Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. · Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. amundadottirl@mail.nih.gov. ·Nat Commun · Pubmed #29422604.

ABSTRACT: In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4). Here, we find significant evidence of a novel association at rs78417682 (7p12/TNS3, P = 4.35 × 10

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