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Pancreatic Neoplasms: HELP
Articles by Raffaele Pezzilli
Based on 72 articles published since 2009
(Why 72 articles?)
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Between 2009 and 2019, R. Pezzilli wrote the following 72 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

Anonymous4750793 / Anonymous4760793 / 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 / Anonymous4770793. ·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 Editorial Pancreatic ductal adenocarcinoma screening: new perspectives. 2012

Pezzilli, Raffaele / Fabbri, Dario / Imbrogno, Andrea. · ·World J Gastroenterol · Pubmed #23049204.

ABSTRACT: Pancreatic ductal adenocarcinoma accounts for more than 90% of all pancreatic cancers and its incidence has increased significantly worldwide. Patients with pancreatic ductal adenocarcinoma have a poor outcome and more than 95% of the people affected die from the disease within 12 mo after diagnosis. Surgery is the first-line treatment in the case of resectable neoplasm, but only 20% of patients are candidates for this approach. One of the reasons there are few candidates for surgery is that, during the early phases of the disease, the symptoms are poor or non-specific. Early diagnosis is of crucial importance to improve patient outcome; therefore, we are looking for a good screening test. The screening test must identify the disease in an early stage in order to be effective; having said this, a need exists to introduce the concept of "early" ductal adenocarcinoma. It has been reported that at least five additional years after the occurrence of the initiating mutation are required for the acquisition of metastatic ability of pancreatic adenocarcinoma and patients die an average of two years thereafter. We have reviewed the most recent literature in order to evaluate the present and future perspectives of screening programs of this deadly disease.

3 Review Role of BAG3 in cancer progression: A therapeutic opportunity. 2018

De Marco, Margot / Basile, Anna / Iorio, Vittoria / Festa, Michelina / Falco, Antonia / Ranieri, Bianca / Pascale, Maria / Sala, Gianluca / Remondelli, Paolo / Capunzo, Mario / Firpo, Matthew A / Pezzilli, Raffaele / Marzullo, Liberato / Cavallo, Pierpaolo / De Laurenzi, Vincenzo / Turco, Maria Caterina / Rosati, Alessandra. ·BIOUNIVERSA s.r.l., R&D Division, Baronissi, SA, 84081, Italy; Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Baronissi, SA, 84081, Italy. · Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Baronissi, SA, 84081, Italy. · BIOUNIVERSA s.r.l., R&D Division, Baronissi, SA, 84081, Italy; Department of Pharmacy, University of Salerno, Fisciano, SA, 84084, Italy. · BIOUNIVERSA s.r.l., R&D Division, Baronissi, SA, 84081, Italy. · Department of Surgery, University of Utah Health Sciences, Salt Lake City, UT, USA. · Department of Digestive Diseases Sant'Orsola-Malpighi Hospital Bologna, Bologna, Italy. · Department of Phisics "E.Caianiello", University of Salerno, Fisciano, SA, 84084, Italy. · BIOUNIVERSA s.r.l., R&D Division, Baronissi, SA, 84081, Italy; Dipartimento di Scienze Mediche, Orali e Biotecnologiche, CeSI, Universita' 'G. D'Annunzio' di Chieti e Pescara, Pescara, Italy. · BIOUNIVERSA s.r.l., R&D Division, Baronissi, SA, 84081, Italy; Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Baronissi, SA, 84081, Italy. Electronic address: mcturco@unisa.it. ·Semin Cell Dev Biol · Pubmed #28864347.

ABSTRACT: BAG3 is a multifunctional protein that can bind to heat shock proteins (Hsp) 70 through its BAG domain and to other partners through its WW domain, proline-rich (PXXP) repeat and IPV (Ile-Pro-Val) motifs. Its intracellular expression can be induced by stressful stimuli, while is constitutive in skeletal muscle, cardiac myocytes and several tumour types. BAG3 can modulate the levels, localisation or activity of its partner proteins, thereby regulating major cell pathways and functions, including apoptosis, autophagy, mechanotransduction, cytoskeleton organisation, motility. A secreted form of BAG3 has been identified in studies on pancreatic ductal adenocarcinoma (PDAC). Secreted BAG3 can bind to a specific receptor, IFITM2, expressed on macrophages, and induce the release of factors that sustain tumour growth and the metastatic process. BAG3 neutralisation therefore appears to constitute a novel potential strategy in the therapy of PDAC and, possibly, other tumours.

4 Review Ki-67 prognostic and therapeutic decision driven marker for pancreatic neuroendocrine neoplasms (PNENs): A systematic review. 2016

Pezzilli, Raffaele / Partelli, Stefano / Cannizzaro, Renato / Pagano, Nico / Crippa, Stefano / Pagnanelli, Michele / Falconi, Massimo. ·Pancreas Unit, Department of Digestive System, Sant'Orsola-Malpighi Hospital, Bologna, Italy. · Pancreatic Surgery Unit, Department of Surgery, San Raffaele Hospital, Milan, Italy. · Department of Gastroenterology, National Cancer Institute, Aviano, Italy. · Pancreatic Surgery Unit, Department of Surgery, San Raffaele Hospital, Milan, Italy. Electronic address: falconi.massimo@hsr.it. ·Adv Med Sci · Pubmed #26774266.

ABSTRACT: BACKGROUND: We systematically evaluate the current evidence regarding Ki-67 as a prognostic factor in pancreatic neuroendocrine neoplasms to evaluate the differences of this marker in primary tumors and in distant metastases as well as the values of Ki-67 obtained by fine needle aspiration and by histology. METHODS: The literature search was carried out using the MEDLINE/PubMed database, and only papers published in the last 10 years were selected. RESULTS: The pancreatic tissue suitable for Ki-67 evaluation was obtained from surgical specimens in the majority of the studies. There was a concordance of 83% between preoperative and postoperative Ki-67 evaluation. Pooling the data of the studies which compared the Ki-67 values obtained in both cytological and surgical specimens, we found that they were not related. The assessment of Ki-67 was manual in the majority of the papers considered for this review. In order to eliminate manual counting, several imaging methods have been developed but none of them are routinely used at present. Twenty-two studies also explored the role of Ki-67 utilized as a prognostic marker for pancreatic neuroendocrine neoplasms and the majority of them showed that Ki-67 is a good prognostic marker of disease progression. Three studies explored the Ki-67 value in metastatic sites and one study demonstrated that, in metachronous and synchronous liver metastases, there was no significant variation in the index of proliferation. CONCLUSIONS: Ki-67 is a reliable prognostic marker for pancreatic neuroendocrine neoplasms.

5 Review Quality assessment of the guidelines on cystic neoplasms of the pancreas. 2015

Falconi, Massimo / Crippa, Stefano / Chari, Suresh / Conlon, Kevin / Kim, Sun-Whe / Levy, Philippe / Tanaka, Masao / Werner, Jens / Wolfgang, Christopher L / Pezzilli, Raffaele / Castillo, Carlos Fernandez-Del. ·Division of Pancreatic Surgery, Università Politecnica delle Marche, Ospedali Riuniti, Ancona, Italy. · Pancreas Interest Group, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA. · Department of Surgery, Trinity College, Dublin, Ireland. · Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea. · Pôle des Maladies de l'Appareil Digestif, Service de Gastroentérologie-Pancréatologie, Hospital Beaujon, APHP, Clichy Cedex, Faculté Denis Diderot, DHU Unity, France. · Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. · Department of Surgery, Ludwig-Maximilian University of Munich, Munich, Germany. · Department of Surgery and The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University, Baltimore, MD, USA. · Pancreas Unit, Department of Digestive System, Sant'Orsola-Malpighi Hospital, Via Massarenti 9, 40138 Bologna, Italy. Electronic address: raffaele.pezzilli@aosp.bo.it. · Pancreas and Biliary Program, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. ·Pancreatology · Pubmed #26100659.

ABSTRACT: BACKGROUND: Though cystic pancreatic neoplasms (CPNs) are being increasingly detected, their evaluation and management are still debated and have lead to publication of multiple guidelines for diagnostic work-up, indications for resection, and non-operative management with follow-up strategies of CPNs. AIMS: To analyze available guidelines in order to evaluate their overall quality and clinical applicability, indications for surgical resection and its extent, modalities and timing of follow-up when non-operative management is indicated. METHODS: After a systematic search of the English literature, we selected eight guidelines for assessment according to the Appraisal of Guidelines, Research and Evaluation in Europe (AGREE) II instrument. RESULTS: One guideline received the lower AGREE score regarding the "scope and purpose", "rigor of development" and "clarity and presentation" domains, whereas one received the best score for "stakeholder involvement" domain. No differences were found among different guidelines regarding the "applicability". The overall quality assessment score showed that only two guidelines were significantly lower than the others. According to the practical utilization recommendation score, four guidelines were considered as having full applicability in clinical practice. CONCLUSION: Existing guidelines provide adequate guidance, at least with the present knowledge, for the management of cystic pancreatic lesions; however, not any one was satisfactory to all aspects related to the management of CPN. An update of the existing guidelines should be considered if and when more evidence-based data are available.

6 Review Alcohol Abuse and Pancreatic Diseases: An Overview. 2015

Pezzilli, Raffaele. ·Pancreas Unit, Department of Digestive System, Sant'Orsola-Malpighi Hospital, Via Massarenti 9, 40138 Bologna, Italy. raffaele.pezzilli@aosp.bo.it. ·Recent Pat Inflamm Allergy Drug Discov · Pubmed #25925405.

ABSTRACT: BACKGROUND: Alcohol is one of the etiological factors of chronic pancreatitis and there is evidence that acute pancreatitis is the first episode of preexisting chronic pancreatitis and is sometimes not evident from a clinical point of view. The diagnosis of acute pancreatitis is based on the presence of abdominal pain, serum increase of pancreatic enzymes or their presence in urine and/or the presence of alterations of the pancreas imaging. AIMS: To revise actual knowledge on the relationship between alcohol use and pancreatic diseases benign as well as malignant. RESULTS: In occasional drinkers, levels of serum amylase were found to be abnormally high in approximately 13% of subjects, while pancreatic isoamylase and lipase were found to be abnormally high in serum in only 2%. The reason might be related to the fact that alcohol can affect the salivary glands. In chronic alcoholics without abdominal pain, amylase and lipase in serum are elevated in 14% of subjects and, in patients with alcoholic acute pancreatitis, pancreatic amylase and isoamylase are elevated in 94% of cases and lipase is generally more sensitive (100% of cases). CONCLUSIONS: Chronic abuse of alcohol, but not occasional alcoholic intoxication, causes pancreatic damage. Regarding pancreatic neoplasms, the role of alcohol is under debate in ductal pancreatic adenocarcinoma as well as in pancreatic neuroendocrine tumors. Few relevant patents are also described in this review.

7 Review Is diabetes mellitus a risk factor for pancreatic cancer? 2013

Pezzilli, Raffaele / Pagano, Nico. ·Department of Digestive Diseases and Internal Medicine, Sant'Orsola-Malpighi Hospital, 40138 Bologna, Italy. raffaele.pezzilli@aosp.bo.it ·World J Gastroenterol · Pubmed #23946590.

ABSTRACT: The relationship between diabetes mellitus and the risk of pancreatic cancer has been a matter of study for a long period of time. The importance of this topic is due to two main causes: the possible use of recent onset diabetes as a marker of the disease and, in particular, as a specific marker of pancreatic cancer, and the selection of a population at risk for pancreatic cancer. Thus, we decided to make an in-depth study of this topic; thus, we carried out an extensive literature search in order to re-assess the current knowledge on this topic. Even if diabetes is found a decade before the appearance of pancreatic cancer as reported in meta-analytic studies, we cannot select those patients already having non detectable pancreatic cancer, at least with the imaging and biological techniques available today. We believe that more studies are necessary in order to definitively identify diabetes mellitus as a risk factor for pancreatic cancer taking into consideration that approximately 10 years are needed to diagnose symptomatic pancreatic cancer. At present, the answer to the as to whether diabetes and pancreatic cancer comes first similar to the adage of the chicken and the egg is that diabetes is the egg.

8 Review Pancreatic mucinous cystic neoplasm in a male patient. 2012

Casadei, Riccardo / Pezzilli, Raffaele / Calculli, Lucia / Santini, Donatella / Taffurelli, Giovanni / Ricci, Claudio / D'Ambra, Marielda / Minni, Francesco. ·Department of Surgery, University of Bologna. Bologna, Italy. riccardo.casadei@unibo.it ·JOP · Pubmed #23183402.

ABSTRACT: CONTEXT: Mucinous cystic neoplasm (MCN) of the pancreas usually affects female patients and is characterized by an ovarian-type stroma. From literature review, only 9 cases of MCNs have been reported in male patients. CASE REPORT: We describe the 10th case of a MCN in a 65-year-old male patient who underwent a distal pancreatectomy with spleen resection and standard lymphadenectomy. CONCLUSIONS: MCN may rarely regard male patients, probably for embryological abnormalities.

9 Review Radiofrequency ablation for advanced ductal pancreatic carcinoma: is this approach beneficial for our patients? A systematic review. 2011

Pezzilli, Raffaele / Serra, Carla / Ricci, Claudio / Casadei, Riccardo / Monari, Francesco / D'Ambra, Marielda / Minni, Francesco. · ·Pancreas · Pubmed #21160378.

ABSTRACT: -- No abstract --

10 Review Total pancreatectomy: indications, operative technique, and results: a single centre experience and review of literature. 2010

Casadei, Riccardo / Monari, Francesco / Buscemi, Salvatore / Laterza, Marco / Ricci, Claudio / Rega, Daniela / D'Ambra, Marielda / Pezzilli, Raffaele / Calculli, Lucia / Santini, Donatella / Minni, Francesco. ·Dipartimento di Scienze Chirurgiche e Anestesiologiche, Chirurgia Generale-Minni, Alma Mater Studiorum, Università di Bologna, Policlinico S.Orsola-Malpighi, Via Massarenti n.9, 40138 Bologna, Italy. riccardo.casadei@aosp.bo.it ·Updates Surg · Pubmed #20845100.

ABSTRACT: The aims of this study were to identify the indications to perform a total pancreatectomy and to evaluate the outcome and quality of life of the patient who underwent this operation. A retrospective analysis of a prospective database, regarding all the patients who underwent total pancreatectomy from January 2006 to June 2009, was carried out. Perioperative and outcome data were analyzed in two different groups: ductal adenocarcinoma (group 1) and non-ductal adenocarcinoma (group 2). Twenty (16.9%) total pancreatectomies out of 118 pancreatic resections were performed. Seven (35.0%) patients were affected by ductal adenocarcinoma (group 1) and the remaining 13 (65.0%) by pancreatic diseases different from ductal adenocarcinoma (group 2) [8 (61.5%) intraductal pancreatic mucinous neoplasms, 2 (15.4%) well-differentiated neuroendocrine carcinomas, 2 (15.4%) pancreatic metastases from renal cell cancer and, finally, 1 (7.7%) chronic pancreatitis]. Eleven patients (55%) underwent primary elective total pancreatectomy; nine (45%) had a completion pancreatectomy previous pancreaticoduodenectomy. Primary elective total pancreatectomy was significantly more frequent in group 2 than in group 1. Early and long-term postoperative results were good without significant difference between the two groups except for the disease-free survival that was significantly better in group 2. The follow-up examinations showed a good control of the apancreatic diabetes and of the exocrine insufficiency without differences between the two groups. In conclusion, currently, total pancreatectomy is a standardized and safe procedure that allows good early and late results. Its indications are increasing because of the more frequent diagnose of pancreatic disease that involved the whole gland as well as intraductal pancreatic mucinous neoplasm, neuroendocrine tumors and pancreatic metastases from renal cell cancer.

11 Review Pancreatic cancer in chronic pancreatitis; aetiology, incidence, and early detection. 2010

Raimondi, Sara / Lowenfels, Albert B / Morselli-Labate, Antonio M / Maisonneuve, Patrick / Pezzilli, Raffaele. ·European Institute of Oncology, Milan, Italy. ·Best Pract Res Clin Gastroenterol · Pubmed #20510834.

ABSTRACT: Acute pancreatitis, chronic pancreatitis and pancreatic cancer are responsible for most of the burden of exocrine pancreatic disease. Glandular damage from recurrent bouts of acute pancreatitis can lead to irreversible changes characteristic of chronic pancreatitis. In recent decades accumulating evidence has defined longstanding pre-existing chronic pancreatitis as a strong risk factor for pancreatic cancer. The lag period between diagnosis of chronic pancreatitis and pancreatic cancer is usually one or two decades: pancreatitis appearing a year or two before the diagnosis of pancreatic cancer is often the result of tumour-related ductal obstruction. The risk of developing pancreatic cancer appears to be highest in rare types of pancreatitis with an early onset, such as hereditary pancreatitis and tropical pancreatitis. Even though there is a strong link between chronic pancreatitis and pancreatic cancer, over a 20 year period only around five percent of patients with chronic pancreatitis will develop pancreatic cancer. Until the development of more sophisticated screening procedures, screening is not recommended for patients with chronic pancreatitis.

12 Clinical Trial Pancreatic endocrine tumors less than 4 cm in diameter: resect or enucleate? a single-center experience. 2010

Casadei, Riccardo / Ricci, Claudio / Rega, Daniela / D'Ambra, Marielda / Pezzilli, Raffaele / Tomassetti, Paola / Campana, Davide / Nori, Francesca / Minni, Francesco. ·Dipartimento di Scienze Chirurgiche e Anestesiologiche, Policlinico S. Orsola-Malpighi, Alma Mater Studiorum Università di Bologna, Bologna, Italy. riccardo.casadei@aosp.bo.it ·Pancreas · Pubmed #20431423.

ABSTRACT: OBJECTIVE: Pancreatic endocrine tumors (PETs) are usually small, benign or low-grade malignant, and surgery should preserve the pancreatic parenchyma as much as possible. The aim of the study was to evaluate the postoperative and long-term survival of patients undergoing enucleation in small PETs. METHODS: Of 82 patients having PETs, 46 with tumor less than 4 cm in diameter, without distant metastases and with R0 resection by final pathologic examination, were included in this study. Enucleation was performed when the tumor did not involve the main pancreatic duct and in the absence of peripancreatic lymphadenopathy (group A); a typical resection was carried out in all other cases (group B). The 2 groups were compared regarding postoperative mortality and morbidity, pancreatic fistula, postoperative hospital stay, reoperation, World Health Organization classification, TNM stage, recurrence, and long-term survival. RESULTS: There were 15 patients (32.6%) in group A and 31 (67.4%) in group B. Postoperative and long-term results were similar in the 2 groups, whereas World Health Organization classification was significantly different; enucleation was performed more frequently than typical R0 resection in benign tumors (P = 0.009). CONCLUSIONS: Enucleation should be reserved for patients having benign PETs less than 4 cm in diameter and far from the main pancreatic duct.

13 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

14 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

15 Article Identification of Small Proteins and Peptides in the Differentiation of Patients with Intraductal Mucinous Neoplasms of the Pancreas, Chronic Pancreatitis and Pancreatic Adenocarcinoma. 2018

Fania, Chiara / Pezzilli, Raffaele / Melzi d'Eril, Gianvico / Gelfi, Cecilia / Barassi, Alessandra. ·Clinical Proteomics Unit, IRCCS Policlinico San Donato, San Donato Milanese, MI, Italy. · Pancreas Unit, Department of Digestive System, Sant'Orsola-Malpighi Hospital, Via Massarenti, 9, 40138, Bologna, Italy. raffaele.pezzilli@aosp.bo.it. · Department of Health Sciences, San Paolo Hospital, University of Milan, Milan, Italy. · Department of Biomedical Sciences for Health, University of Milan, Milan, Italy. ·Dig Dis Sci · Pubmed #29417328.

ABSTRACT: BACKGROUND: There are a limited number of studies investigating the type of serum proteins capable of differentiating intraductal papillary mucinous neoplasms from benign or malignant diseases of the pancreas. AIMS: To select proteins able to differentiate intraductal papillary mucinous neoplasms from benign and malignant pancreatic disease using semiquantitative proteomics. METHODS: Serum samples were obtained from 74 patients (19 with type II intraductal papillary mucinous neoplasms, 8 with type I/III intraductal papillary mucinous neoplasms, 24 with chronic pancreatitis, 23 with pancreatic ductal adenocarcinomas) and 21 healthy subjects. Small proteins and peptides were assayed by matrix-assisted laser desorption/ionization for the detection of differentially abundant species possibly related to tumor onset. Serum pancreatic amylase, lipase, carcinoembryonic antigen and carbohydrate antigen 19-9 (CA 19-9) were also assayed. RESULTS: Twenty-six of 84 peaks detected were dysregulated (7 more abundant and 19 less abundant in the type II intraductal papillary mucinous neoplasms, p < 0.05). Of the differentially abundant peaks, 17 were commonly dysregulated (3 peaks more abundant and 13 less abundant in type II intraductal papillary mucinous neoplasms, and one at  m/z = 9961 at variance), indicating a protein fingerprint shared by types I/III and type II intraductal papillary mucinous neoplasms and pancreatic ductal adenocarcinomas. CONCLUSIONS: These results suggest that our approach can be used to differentiate type II intraductal papillary mucinous neoplasms from type I/III neoplasms, and type II intraductal papillary mucinous neoplasms from pancreatic ductal adenocarcinomas.

16 Article Do pancreatic cancer and chronic pancreatitis share the same genetic risk factors? A PANcreatic Disease ReseArch (PANDoRA) consortium investigation. 2018

Campa, Daniele / Pastore, Manuela / Capurso, Gabriele / Hackert, Thilo / Di Leo, Milena / Izbicki, Jakob R / Khaw, Kay-Tee / Gioffreda, Domenica / Kupcinskas, Juozas / Pasquali, Claudio / Macinga, Peter / Kaaks, Rudolf / Stigliano, Serena / Peeters, Petra H / Key, Timothy J / Talar-Wojnarowska, Renata / Vodicka, Pavel / Valente, Roberto / Vashist, Yogesh K / Salvia, Roberto / Papaconstantinou, Ioannis / Shimizu, Yasuhiro / Valsuani, Chiara / Zambon, Carlo Federico / Gazouli, Maria / Valantiene, Irena / Niesen, Willem / Mohelnikova-Duchonova, Beatrice / Hara, Kazuo / Soucek, Pavel / Malecka-Panas, Ewa / Bueno-de-Mesquita, H B As / Johnson, Theron / Brenner, Herman / Tavano, Francesca / Fogar, Paola / Ito, Hidemi / Sperti, Cosimo / Butterbach, Katja / Latiano, Anna / Andriulli, Angelo / Cavestro, Giulia Martina / Busch, Olivier R C / Dijk, Frederike / Greenhalf, William / Matsuo, Keitaro / Lombardo, Carlo / Strobel, Oliver / König, Anna-Katharina / Cuk, Katarina / Strothmann, Hendrik / Katzke, Verena / Cantore, Maurizio / Mambrini, Andrea / Oliverius, Martin / Pezzilli, Raffaele / Landi, Stefano / Canzian, Federico. ·Department of Biology, University of Pisa, Pisa, Italy. · Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Digestive and Liver Disease Unit, S. Andrea Hospital 'Sapienza' University of Rome, Rome, Italy. · Department of General Surgery, University Hospital Heidelberg, Heidelberg, Germany. · Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan, Italy. · Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. · Clinical Gerontology Unit, Addenbrooke's Hospital, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom. · Division of Gastroenterology and Research Laboratory, Department of Surgery, IRCCS Scientific Institute and Regional General Hospital "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy. · Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania. · Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padova, Padova, Italy. · Institute of Experimental Medicine, Czech Academy of Sciences and Institute of Clinical and Experimental Medicine, Prague, Czech Republic. · Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. · MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, United Kingdom. · Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom. · Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland. · Department of Visceral Surgery, Kantonsspital Aarau AG, Aarau, Switzerland. · Department of Surgery, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy. · Second Department of Surgery, Aretaieion Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. · Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Nagoya, Japan. · Oncological Department, Azienda USL Toscana Nord Ovest, Oncological Unit of Massa Carrara, Carrara, Massa and Carrara, Italy. · Department of Medicine (DIMED), University of Padova, Padova, Italy. · Department of Basic Medical Sciences, Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. · Department of Oncology, Palacky University Medical School and Teaching Hospital, Olomouc, Czech Republic. · Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan. · Biomedical Center, Faculty of Medicine in Pilsen, Charles University in Prague, Pilsen, Czech Republic. · Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment, Bilthoven, The Netherlands. · Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, St Mary's Campus, London, United Kingdom. · Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. · Division of Clinical Epidemiology, 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. · Department of Laboratory Medicine, University-Hospital of Padova, Padova, Italy. · Division of Molecular and Clinical Epidemiology, Aichi Cancer Center Research Institute, Nagoya, Japan. · Department of Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan. · Department of Surgery, Academic Medical Centre, Amsterdam, the Netherlands. · Department of Pathology, Academic Medical Centre, Amsterdam, the Netherlands. · Institute for Health Research, Liverpool Pancreas Biomedical Research Unit, University of Liverpool, Liverpool, United Kingdom. · Division of General and Transplant Surgery, University of Pisa, Pisa, Italy. · Dipartimento di Ricerca Traslazionale e delle Nuove Tecnologie in Medicina e Chirurgia, University of Pisa, Pisa, Italy. · Transplant Surgery Department, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. · Pancreas Unit, Department of Digestive Diseases and Internal Medicine Sant'Orsola-Malpighi Hospital, Bologna, Italy. ·Int J Cancer · Pubmed #28913878.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is a very aggressive tumor with a five-year survival of less than 6%. Chronic pancreatitis (CP), an inflammatory process in of the pancreas, is a strong risk factor for PDAC. Several genetic polymorphisms have been discovered as susceptibility loci for both CP and PDAC. Since CP and PDAC share a consistent number of epidemiologic risk factors, the aim of this study was to investigate whether specific CP risk loci also contribute to PDAC susceptibility. We selected five common SNPs (rs11988997, rs379742, rs10273639, rs2995271 and rs12688220) that were identified as susceptibility markers for CP and analyzed them in 2,914 PDAC cases, 356 CP cases and 5,596 controls retrospectively collected in the context of the international PANDoRA consortium. We found a weak association between the minor allele of the PRSS1-PRSS2-rs10273639 and an increased risk of developing PDAC (OR

17 Article Response to Malleo et al. 2017

Crippa, Stefano / Pezzilli, Raffaele / Capurso, Gabriele / Ruffo, Giacomo / Falconi, Massimo. ·Department of Surgery, Sacro Cuore-Don Calabria Hospital, Verona, Italy. · Division of Pancreatic Surgery, Pancreas Translational &Clinical Research Center, Università Vita-Salute, San Raffaele Scientisfic Institute, Milan, Italy. · Department of Digestive System, Pancreas Unit, Sant'Orsola-Malpighi Hospital, Bologna, Italy. · Digestive and Liver Disease Unit, S. Andrea Hospital, University Sapienza, Rome, Italy. ·Am J Gastroenterol · Pubmed #28874865.

ABSTRACT: -- No abstract --

18 Article Comparison of Clinical Data and Scores of Quality of Life, Anxiety, and Depression in Patients With Different Types of Intraductal Papillary Mucinous Neoplasms: A Prospective Study. 2017

Pezzilli, Raffaele / Cucchetti, Alessandro / Calculli, Lucia. ·From the *Pancreas Unit, Department of Digestive System, Sant'Orsola-Malpighi Hospital; †Department of Medical and Surgical Sciences, University of Bologna; ‡Department of Diagnostic Medicine and Prevention, Sant'Orsola-Malpighi Hospital, Bologna, Italy. ·Pancreas · Pubmed #28787332.

ABSTRACT: OBJECTIVES: This study aims to evaluate the well-being of patients with main duct intraductal papillary mucinous neoplasms (MD-IPMNs) or mixed type IPMNs (mixed-IPMNs) of the pancreas. METHODS: Twenty-two patients with MD/mixed-IPMNs of the pancreas were studied, and an equal number of patients having branch duct IPMNs (BD-IPMNs) were used as controls. The short form (SF) -12 Health Survey, State Trait Anxiety Inventory Y-1 and Y-2, General Health Questionnaire, and Beck Depression Inventory II were used to evaluate the quality of life once a year for 2 consecutive years. RESULTS: At basal evaluation, the SF-12 Health Survey questionnaire administered to the 44 patients showed that the values of the physical component and mental component scores were similar between the 2 groups of patients studied. The State Trait Anxiety Inventory Y-1 and Y-2, General Health Questionnaire, and Beck Depression Inventory II scores were also similar in the 2 groups at basal evaluation. No differences were found between MD/mixed-IPMNs and BD-IPMNs at the 1-year and the 2-year evaluations. CONCLUSIONS: The well-being of patients with MD/mixed-IPMNs did not differ as compared with patients with BD-IPMNs.

19 Article Serum endocannabinoids in assessing pain in patients with chronic pancreatitis and in those with pancreatic ductal adenocarcinoma. 2017

Pezzilli, Raffaele / Ciuffreda, Pierangela / Ottria, Roberta / Ravelli, Alessandro / Melzi d'Eril, Gianvico / Barassi, Alessandra. ·a Department of Digestive Diseases , Sant'Orsola-Malpighi Hospital , Bologna , Italy. · b L. Sacco, Department of Biomedical and Clinical Sciences , University of Milan , Milan , Italy. · c Department of Biomedical, Surgical and Dental Sciences , University of Milan , Milan , Italy. · d Department of Health Sciences , San Paolo Hospital, University of Milan , Milan , Italy. ·Scand J Gastroenterol · Pubmed #28631495.

ABSTRACT: BACKGROUND: The endocannabinoid system plays a substantial role in analgesia. AIM: To analyze N-arachidonoylethanolamine (AEA), N-oleoylethanolamine (OEA), linoleoyl ethanolamide (LEA), α-linoleoyl ethanolamine (α-LNEA), N-palmitoylethanolamine (PEA) and N-stearoyl ethanolamine (SEA) in two groups of patients having chronic pancreatic diseases. PATIENTS AND METHODS: Twenty-six patients with chronic pancreatitis, 26 patients with pancreatic ductal adenocarcinoma and 36 healthy subjects were studied. The visual analogic scale (VAS) was used for assessing pain immediately before the venipuncture to obtain blood in all subjects. Six endocannabinoids were measured in serum of the patients enrolled. RESULTS: Only OEA, LEA and PEA serum levels were significantly higher in patients with pain as compared to those without. Using the cutoff values, the sensitivity and specificity of the various endocannabinoids in evaluating pain in patients with chronic pancreatitis and in those with pancreatic ductal adenocarcinoma were: 44.2% and 95.6% for AEA, 83.7% and 73.3% for LEA, 88.4% and 91.1% for LNEA, 81.4% and 82.2% for OEA, 81.4% and 88.9% for PEA, 86.0% and 88.9% for SEA, respectively. CONCLUSION: Endocannabinoids are not useful in assessing pain in patients with chronic pancreatic diseases and they cannot replace a simple method such as VAS for assessing the pain and its intensity.

20 Article SLC22A3 polymorphisms do not modify pancreatic cancer risk, but may influence overall patient survival. 2017

Mohelnikova-Duchonova, Beatrice / Strouhal, Ondrej / Hughes, David J / Holcatova, Ivana / Oliverius, Martin / Kala, Zdenek / Campa, Daniele / Rizzato, Cosmeri / Canzian, Federico / Pezzilli, Raffaele / Talar-Wojnarowska, Renata / Malecka-Panas, Ewa / Sperti, Cosimo / Federico Zambon, Carlo / Pedrazzoli, Sergio / Fogar, Paola / Milanetto, Anna Caterina / Capurso, Gabriele / Delle Fave, Gianfranco / Valente, Roberto / Gazouli, Maria / Malleo, Giuseppe / Teresa Lawlor, Rita / Strobel, Oliver / Hackert, Thilo / Giese, Nathalia / Vodicka, Pavel / Vodickova, Ludmila / Landi, Stefano / Tavano, Francesca / Gioffreda, Domenica / Piepoli, Ada / Pazienza, Valerio / Mambrini, Andrea / Pedata, Mariangela / Cantore, Maurizio / Bambi, Franco / Ermini, Stefano / Funel, Niccola / Lemstrova, Radmila / Soucek, Pavel. ·Department of Toxicogenomics, National Institute of Public Health, Prague, Czech Republic. · Department of Oncology, Palacky University Medical School and Teaching Hospital, Olomouc, Czech Republic. · Department of Physiology &Centre for Systems Medicine, Royal College of Surgeons in Ireland, Dublin 2, Ireland. · Institute of Hygiene and Epidemiology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic. · Department of Transplantation Surgery, Institute of Clinical and Experimental Medicine, Prague, Czech Republic. · Department of Surgery, The University Hospital and Faculty of Medicine, Brno Bohunice, Czech Republic. · Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Department of Biology, University of Pisa, Pisa, Italy. · Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy. · Department of Digestive Diseases, Sant'Orsola-Malpighi Hospital, Bologna, Italy. · Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland. · Department of Surgery, Oncology and Gastroenterology -DiSCOG, University of Padova, Italy. · Department of Medicine - DIMED, University of Padova, Italy. · Clinica Chirurgica 4, University of Padova, Italy. · Department of Laboratory Medicine, University-Hospital of Padova, Italy. · Digestive and Liver Disease Unit, S. Andrea Hospital, 'Sapienza' University of Rome, Rome, Italy. · Department of Basic Medical Sciences, Laboratory of Biology, School of Medicine, University of Athens, Athens, Greece. · Department of Surgery and Oncology, University and Hospital Trust of Verona, Verona, Italy. · ARC-NET Applied research on Cancer Centre, University and Hospital Trust of Verona, Verona, Italy. · Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany. · Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Science of Czech Republic, Prague, Czech Republic and First Faculty of Medicine, Charles University in Prague, Czech Republic. · Biomedical Centre, Faculty of Medicine in Pilsen, Charles University in Prague, Pilsen, Czech Republic. · Division of Gastroenterology and Research Laboratory, IRCCS Scientific Institute and Regional General Hospital "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy. · Department of Oncology, Azienda USL 1 Massa Carrara, Massa Carrara, Italy. · Blood Transfusion Service, Children's Hospital Meyer, Azienda Ospedaliero Universitaria, Florence, Italy. ·Sci Rep · Pubmed #28272475.

ABSTRACT: Expression of the solute carrier (SLC) transporter SLC22A3 gene is associated with overall survival of pancreatic cancer patients. This study tested whether genetic variability in SLC22A3 associates with pancreatic cancer risk and prognosis. Twenty four single nucleotide polymorphisms (SNPs) tagging the SLC22A3 gene sequence and regulatory elements were selected for analysis. Of these, 22 were successfully evaluated in the discovery phase while six significant or suggestive variants entered the validation phase, comprising a total study number of 1,518 cases and 3,908 controls. In the discovery phase, rs2504938, rs9364554, and rs2457571 SNPs were significantly associated with pancreatic cancer risk. Moreover, rs7758229 associated with the presence of distant metastases, while rs512077 and rs2504956 correlated with overall survival of patients. Although replicated, the association for rs9364554 did not pass multiple testing corrections in the validation phase. Contrary to the discovery stage, rs2504938 associated with survival in the validation cohort, which was more pronounced in stage IV patients. In conclusion, common variation in the SLC22A3 gene is unlikely to significantly contribute to pancreatic cancer risk. The rs2504938 SNP in SLC22A3 significantly associates with an unfavorable prognosis of pancreatic cancer patients. Further investigation of this SNP effect on the molecular and clinical phenotype is warranted.

21 Article Active Surveillance Beyond 5 Years Is Required for Presumed Branch-Duct Intraductal Papillary Mucinous Neoplasms Undergoing Non-Operative Management. 2017

Crippa, Stefano / Pezzilli, Raffaele / Bissolati, Massimiliano / Capurso, Gabriele / Romano, Luigi / Brunori, Maria Paola / Calculli, Lucia / Tamburrino, Domenico / Piccioli, Alessandra / Ruffo, Giacomo / Fave, Gianfranco Delle / Falconi, Massimo. ·Department of Surgery, Sacro Cuore-Don Calabria Hospital, Negrar, Verona, Italy. · Pancreas Translational &Clinical Research Center, Division of Pancreatic Surgery, Università Vita-Salute, San Raffaele Scientific Institute, Milan, Italy. · Pancreas Unit, Department of Digestive System, Sant'Orsola-Malpighi Hospital, Bologna, Italy. · Division of Transplant Surgery, San Raffaele Scientific Institute, Milan, Italy. · Digestive and Liver Disease Unit, S. Andrea Hospital, University Sapienza, Rome, Italy. · Department of Radiology, Sacro Cuore-Don Calabria Hospital, Negrar, Verona, Italy. · Division of Gastroenterology, Sacro Cuore-Don Calabria Hospital, Negrar, Verona, Italy. · Department of Radiology, Sant'Orsola-Malpighi Hospital, Bologna, Italy. · Department of Surgery, Università Politecnica delle Marche, Ancona, Italy. ·Am J Gastroenterol · Pubmed #28244498.

ABSTRACT: OBJECTIVES: To evaluate the results of active surveillance beyond 5 years in patients with branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) without worrisome features (WF) and high-risk stigmata (HRS) undergoing non-operative management. METHODS: Patients with a minimum follow-up of 5 years who underwent surveillance with at least yearly magnetic resonance imaging were included. New onset of and predictors of WF/HRS during follow-up as well as long-term survival were analyzed. RESULTS: In all, 144 patients were followed for a median of 84 months. At diagnosis multifocal BD-IPMNs were found in 53% of cases and mean size of the largest cyst was 15.5 mm. Changes during follow-up were observed in 69 patients (48%). New onset of WF/HRS were observed in 26 patients (18%) but the rate of HRS was only 4%. WF and HRS developed after a median follow-up of 71 and 77.5 months from diagnosis, respectively, and without previous changes in 19/26 patients. Independent predictors of WF/HRS development were size at diagnosis>15 mm, increase in number of lesions, main pancreatic duct growth rate ≥0.2 mm/year, cyst growth rate >1 mm/year. Overall, the rate of pancreatic invasive malignancy was 2% and the 12-year disease-specific survival was 98.6%. CONCLUSIONS: Long-term nonoperative management is safe for BD-IPMNs without WF and HRS. Discontinuation of surveillance cannot be recommended since one out of six patients developed WF/HRS far beyond 5 years of surveillance and without previous relevant modifications. An intensification of follow-up should be considered after 5 years.

22 Article The Health Gain Obtainable from Pancreatic Resection for Adenocarcinoma in the Elderly. 2017

Cucchetti, Alessandro / Ercolani, Giorgio / Pezzilli, Raffaele / Cescon, Matteo / Frascaroli, Giacomo / Pinna, Antonio Daniele. ·Department of Medical and Surgical Sciences - DIMEC, S.Orsola - Malpighi Hospital, Alma Mater Studiorum, University of Bologna, Bologna, Italy. aleqko@libero.it. · S. Orsola-Malpighi Hospital, Via Massarenti 9, 40138, Bologna, Italy. aleqko@libero.it. · Department of Medical and Surgical Sciences - DIMEC, S.Orsola - Malpighi Hospital, Alma Mater Studiorum, University of Bologna, Bologna, Italy. · Surgical Oncology Unit, General Hospital Morgagni - Pierantoni, Forlì, Italy. · S. Orsola-Malpighi Hospital, Via Massarenti 9, 40138, Bologna, Italy. ·World J Surg · Pubmed #27826771.

ABSTRACT: BACKGROUND: In treating pancreatic ductal adenocarcinoma (PDAC), age does not represent a contraindication to surgery, even if aging is known to increase postoperative mortality and morbidity. Furthermore, long-term outcome remains poor and there is much debate on whether to operate or not in elderly patients. The aim of this study was to provide a general framework to evaluate the health gain obtainable from surgery for PDAC in relationship with age and tumor stage. METHODS: A Monte Carlo simulation model was built taking into consideration pertinent literature from population-based studies regarding surgical and non-surgical outcomes for stages I-II PDAC. The health gain obtainable from surgery, in comparison to the choice of not resecting patients, was measured through number needed-to-treat (NNT) calculation. RESULTS: Considering the typical stage I-II PDAC characteristics, the model showed that the mean lifespan after surgery was 28.1 ± 3.9 months and 9.3 ± 1.5 months after non-surgical therapies. The NNT with surgery in order to prevent one death at 5 years was 6 (95% CI 4-10), indicating an overall high gain obtainable from surgery. Sensitivity analyses on patient age and tumor stage suggested that starting from 76 years onward, the NNT progressively increases, resulting in a low cure rate of surgery in the elderly and becoming potentially harmful for patients aged above 80 years. These figures were more pronounced for tumor stages IIA and IIB. CONCLUSIONS: The present general framework suggests that the lifespan benefit obtainable from pancreatectomy in elderly patients is uncertain especially with the advancing of the tumor stage.

23 Article Can Serum Pancreatic Amylase and Lipase Levels Be Used as Diagnostic Markers to Distinguish Between Patients With Mucinous Cystic Lesions of the Pancreas, Chronic Pancreatitis, and Pancreatic Ductal Adenocarcinoma? 2016

Pezzilli, Raffaele / Melzi dʼEril, Gianvico / Barassi, Alessandra. ·From the *Department of Digestive System, Sant'Orsola-Malpighi Hospital, Bologna; and †Department of Health Sciences, San Paolo Hospital, University of Milan, Milan, Italy. ·Pancreas · Pubmed #27776046.

ABSTRACT: OBJECTIVE: This study aimed to assess the presence of pancreatic hyperenzymemia in patients with pancreatic cystic lesions as compared to other chronic diseases of the pancreas. METHODS: Ninety-one patients were studied: 32 had mucinous cystic lesions, 35 had chronic pancreatitis (CP), and 24 had pancreatic ductal adenocarcinoma (PDAC). Surgery was carried out in 10 of the 32 patients with mucinous cystic lesion (7 of them had severe dysplasia), in 5 patients with CP, and in 9 patients with PDAC. RESULTS: Abnormally high serum pancreatic isoamylase activity was present in 11 (34.4%) patients with mucinous cystic lesions, in 14 (40.0%) patients with CP, and none in patients with PDAC (P = 0.002); whereas serum lipase activity was abnormally high in 8 (25.0%) patients with mucinous cystic lesion, in 17 (48.6%) patients with CP, and in 3 (12.5%) patients with PDAC (P = 0.009). In 7 patients with mucinous cystic lesions and histologically confirmed severe dysplasia, abnormally high levels of both serum pancreatic amylase and lipase were present in 3 (42.9%) patients. CONCLUSIONS: High serum concentrations of pancreatic amylase and lipase were found in no more than half of the patients with mucinous cystic lesions. High levels of pancreatic enzymes were not associated with a greater risk of malignancy.

24 Article Serum tumor markers not useful in screening patients with pancreatic mucinous cystic lesions associated with malignant changes. 2016

Pezzilli, Raffaele / Calculli, Lucia / Melzi d'Eril, Gianvico / Barassi, Alessandra. ·Department of Digestive System, Sant'Orsola-Malpighi Hospital, Via Massarenti 9, Bologna 40138, Italy. raffaele.pezzilli@aosp.bo.it. ·Hepatobiliary Pancreat Dis Int · Pubmed #27733327.

ABSTRACT: BACKGROUND: Serum cancer antigen 19-9 (CA19-9) provides additional information about mucinous cystic pancreatic neoplasm (MPN). This study was undertaken to assess both CA19-9 and carcinoembryonic antigen (CEA) serum concentrations in consecutive patients affected by MPNs and other chronic benign and malignant pancreatic diseases. We also evaluated whether serum CA19-9 and CEA determinations provide additional information such as the presence of invasive carcinoma in MPN patients. METHODS: Serum CA19-9 and CEA from 91 patients with pancreatic diseases were tested by commercially available kits at the time of diagnosis. The upper reference limit of serum CA19-9 was 37 U/mL and that of serum CEA was 3 ng/mL. RESULTS: Thirty-five patients was diagnosed with chronic pancreatitis (CP), 32 with MPN, and 24 with pancreatic ductal adenocarcinoma (PDAC) confirmed histologically. Surgery was carried out in 5 CP patients, in 10 MPN patients (7 of them had severe dysplasia), and in 9 PDAC patients. Serum CA19-9 activity was high in 12 (34.3%) CP patients, in 7 (21.9%) MPN patients, and in 12 (50.0%) PDAC patients (P=0.089). High serum CEA concentrations were noted in 6 (17.1%) CP patients, in 6 (18.8%) MPN patients, and in 12 (50.0%) PDAC patients (P=0.010). In the 7 MPN patients associated with histologically confirmed severe dysplasia, 3 (42.9%) patients had elevated serum activity of serum CA19-9, and 2 (28.6%) patients had high levels of CEA. CONCLUSION: Serum determination of oncological markers is not useful in selecting MPN patients with malignant changes.

25 Article Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21. 2016

Zhang, Mingfeng / Wang, Zhaoming / Obazee, Ofure / Jia, Jinping / Childs, Erica J / Hoskins, Jason / Figlioli, Gisella / Mocci, Evelina / Collins, Irene / Chung, Charles C / Hautman, Christopher / Arslan, Alan A / Beane-Freeman, Laura / Bracci, Paige M / Buring, Julie / Duell, Eric J / Gallinger, Steven / Giles, Graham G / Goodman, Gary E / Goodman, Phyllis J / Kamineni, Aruna / Kolonel, Laurence N / Kulke, Matthew H / Malats, Núria / Olson, Sara H / Sesso, Howard D / Visvanathan, Kala / White, Emily / Zheng, Wei / Abnet, Christian C / Albanes, Demetrius / Andreotti, Gabriella / Brais, Lauren / Bueno-de-Mesquita, H Bas / Basso, Daniela / Berndt, Sonja I / Boutron-Ruault, Marie-Christine / Bijlsma, Maarten F / Brenner, Hermann / Burdette, Laurie / Campa, Daniele / Caporaso, Neil E / Capurso, Gabriele / Cavestro, Giulia Martina / Cotterchio, Michelle / Costello, Eithne / Elena, Joanne / Boggi, Ugo / Gaziano, J Michael / Gazouli, Maria / Giovannucci, Edward L / Goggins, Michael / Gross, Myron / Haiman, Christopher A / Hassan, Manal / Helzlsouer, Kathy J / Hu, Nan / Hunter, David J / Iskierka-Jazdzewska, Elzbieta / Jenab, Mazda / Kaaks, Rudolf / Key, Timothy J / Khaw, Kay-Tee / Klein, Eric A / Kogevinas, Manolis / Krogh, Vittorio / Kupcinskas, Juozas / Kurtz, Robert C / Landi, Maria T / Landi, Stefano / Le Marchand, Loic / Mambrini, Andrea / Mannisto, Satu / Milne, Roger L / Neale, Rachel E / Oberg, Ann L / Panico, Salvatore / Patel, Alpa V / Peeters, Petra H M / Peters, Ulrike / Pezzilli, Raffaele / Porta, Miquel / Purdue, Mark / Quiros, J Ramón / Riboli, Elio / Rothman, Nathaniel / Scarpa, Aldo / Scelo, Ghislaine / Shu, Xiao-Ou / Silverman, Debra T / Soucek, Pavel / Strobel, Oliver / Sund, Malin / Małecka-Panas, Ewa / Taylor, Philip R / Tavano, Francesca / Travis, Ruth C / Thornquist, Mark / Tjønneland, Anne / Tobias, Geoffrey S / Trichopoulos, Dimitrios / Vashist, Yogesh / Vodicka, Pavel / Wactawski-Wende, Jean / Wentzensen, Nicolas / Yu, Herbert / Yu, Kai / Zeleniuch-Jacquotte, Anne / Kooperberg, Charles / Risch, Harvey A / Jacobs, Eric J / Li, Donghui / Fuchs, Charles / Hoover, Robert / Hartge, Patricia / Chanock, Stephen J / Petersen, Gloria M / Stolzenberg-Solomon, Rachael S / Wolpin, Brian M / Kraft, Peter / Klein, Alison P / Canzian, Federico / Amundadottir, Laufey T. ·Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. · Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. · Cancer Genomics Research Laboratory, National Cancer Institute, Division of Cancer Epidemiology and Genetics, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA. · Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. · Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Department of Oncology, the Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. · Department of Obstetrics and Gynecology, New York University School of Medicine, New York, New York, USA. · Department of Environmental Medicine, New York University School of Medicine, New York, New York, USA. · New York University Cancer Institute, New York, New York, USA,. · Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, USA. · Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. · Division of Aging, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. · Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Bellvitge Biomedical Research Institute (IDIBELL), Catalan Institute of Oncology (ICO), Barcelona, Spain. · Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada. · Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia. · Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria, Australia. · Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia. · Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. · Southwest Oncology Group Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. · Group Health Research Institute, Seattle, Washington, USA,. · Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, USA. · Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. · Genetic and Molecular Epidemiology Group, CNIO-Spanish National Cancer Research Centre, Madrid, Spain. · Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA. · Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. · Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. · Department of Epidemiology, University of Washington, Seattle, Washington, USA. · Division of Epidemiology, Vanderbilt University Medical Center, Nashville, Tennessee, USA. · Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA. · Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. · Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom. · Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. · Department of Laboratory Medicine, University Hospital of Padova, Padua, Italy,. · Inserm, Centre for Research in Epidemiology and Population Health (CESP), U1018, Nutrition, Hormones and Women's Health Team, F-94805, Villejuif, France. · University Paris Sud, UMRS 1018, F-94805, Villejuif, France. · IGR, F-94805, Villejuif, France. · Laboratory for Experimental Oncology and Radiobiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. · 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. · Department of Biology, University of Pisa, Pisa, Italy. · Digestive and Liver Disease Unit, 'Sapienza' University of Rome, Rome, Italy. · Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy. · Prevention and Cancer Control, Cancer Care Ontario, Toronto, Ontario, Canada. · Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada. · National Institute for Health Research Liverpool Pancreas Biomedical Research Unit, University of Liverpool, Liverpool, United Kingdom. · Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. · Department of Surgery, Unit of Experimental Surgical Pathology, University Hospital of Pisa, Pisa, Italy. · Massachusetts Veteran's Epidemiology, Research, and Information Center, Geriatric Research Education and Clinical Center, Veterans Affairs Boston Healthcare System, Boston, Massachusetts, USA. · Department of Basic Medical Sciences, Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, Athens, Greece. · Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA. · Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA. · Department of Pathology, Sidney Kimmel Cancer Center and Johns Hopkins University, Baltimore, Maryland, USA. · Department of Medicine, Sidney Kimmel Cancer Center and Johns Hopkins University, Baltimore, Maryland, USA. · Department of Oncology, Sidney Kimmel Cancer Center and Johns Hopkins University, Baltimore, Maryland, USA. · Laboratory of Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USA. · Preventive Medicine, University of Southern California, Los Angeles, California, USA. · Department of Gastrointestinal Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA. · Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. · Harvard School of Public Health, Boston, Massachusetts, USA. · Harvard Medical School, Boston, Massachusetts, USA. · Department of Hematology, Medical University of Łodz, Łodz, Poland. · International Agency for Research on Cancer (IARC), Lyon, France. · Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Cancer Epidemiology Unit, University of Oxford, Oxford, United Kingdom. · School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom. · Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio, USA. · Centre de Recerca en Epidemiologia Ambiental (CREAL), CIBER Epidemiología y Salud Pública (CIBERESP), Spain. · Hospital del Mar Institute of Medical Research (IMIM), Barcelona, Spain. · National School of Public Health, Athens, Greece. · Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. · Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania. · Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USA. · Oncology Department, ASL1 Massa Carrara, Massa Carrara, Italy. · National Institute for Health and Welfare, Department of Chronic Disease Prevention, Helsinki, Finland. · Department of Population Health, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. · Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA. · Dipartimento di Medicina Clinica E Chirurgia, Federico II Univeristy, Naples, Italy. · Epidemiology Research Program, American Cancer Society, Atlanta, Georgia, USA. · Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. · Pancreas Unit, Department of Digestive Diseases and Internal Medicine, Sant'Orsola-Malpighi Hospital, Bologna, Italy. · School of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain. · CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. · Public Health and Participation Directorate, Asturias, Spain. · ARC-NET: Centre for Applied Research on Cancer, University and Hospital Trust of Verona, Verona, Italy. · Laboratory of Pharmacogenomics, Biomedical Center, Faculty of Medicine in Pilsen, Charles University in Prague, Pilsen, Czech Republic. · Department of General Surgery, University Hospital Heidelberg, Heidelberg, Germany. · Department of Surgical and Peroperative Sciences, Umeå University, Umeå, Sweden. · Department of Digestive Tract Diseases, Medical University of Łodz, Łodz, Poland. · Division of Gastroenterology and Research Laboratory, IRCCS Scientific Institute and Regional General Hospital "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy. · Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark. · Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. · Hellenic Health Foundation, Athens, Greece. · Department of General, Visceral and Thoracic Surgery, University Hamburg-Eppendorf, Hamburg, Germany. · Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic. · Department of Social and Preventive Medicine, University at Buffalo, Buffalo, New York, USA. · New York University Cancer Institute, New York, New York, USA. · Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA,. · Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut, USA. · Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA. · Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA. · Department of Epidemiology, the Bloomberg School of Public Health, Baltimore, Maryland, USA. ·Oncotarget · Pubmed #27579533.

ABSTRACT: Genome-wide association studies (GWAS) have identified common pancreatic cancer susceptibility variants at 13 chromosomal loci in individuals of European descent. To identify new susceptibility variants, we performed imputation based on 1000 Genomes (1000G) Project data and association analysis using 5,107 case and 8,845 control subjects from 27 cohort and case-control studies that participated in the PanScan I-III GWAS. This analysis, in combination with a two-staged replication in an additional 6,076 case and 7,555 control subjects from the PANcreatic Disease ReseArch (PANDoRA) and Pancreatic Cancer Case-Control (PanC4) Consortia uncovered 3 new pancreatic cancer risk signals marked by single nucleotide polymorphisms (SNPs) rs2816938 at chromosome 1q32.1 (per allele odds ratio (OR) = 1.20, P = 4.88x10 -15), rs10094872 at 8q24.21 (OR = 1.15, P = 3.22x10 -9) and rs35226131 at 5p15.33 (OR = 0.71, P = 1.70x10 -8). These SNPs represent independent risk variants at previously identified pancreatic cancer risk loci on chr1q32.1 ( NR5A2), chr8q24.21 ( MYC) and chr5p15.33 ( CLPTM1L- TERT) as per analyses conditioned on previously reported susceptibility variants. We assessed expression of candidate genes at the three risk loci in histologically normal ( n = 10) and tumor ( n = 8) derived pancreatic tissue samples and observed a marked reduction of NR5A2 expression (chr1q32.1) in the tumors (fold change -7.6, P = 5.7x10 -8). This finding was validated in a second set of paired ( n = 20) histologically normal and tumor derived pancreatic tissue samples (average fold change for three NR5A2 isoforms -31.3 to -95.7, P = 7.5x10 -4-2.0x10 -3). Our study has identified new susceptibility variants independently conferring pancreatic cancer risk that merit functional follow-up to identify target genes and explain the underlying biology.

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