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Pancreatic Neoplasms: HELP
Articles by Angelo Andriulli
Based on 20 articles published since 2009
(Why 20 articles?)
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Between 2009 and 2019, Angelo Andriulli wrote the following 20 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Review Exploring the microbiota to better understand gastrointestinal cancers physiology. 2018

Panebianco, Concetta / Potenza, Adele / Andriulli, Angelo / Pazienza, Valerio. ·Gastroenterology Unit, IRCCS "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo (FG), Italy. · Dietetic and Clinical Nutrition Unit IRCCS "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo (FG), Italy. · Gastroenterology Unit, IRCCS "Casa Sollievo della Sofferenza" Hospital, Viale dei Cappuccini, 1, 71013 San Giovanni Rotondo (FG), Italy, Phone: +39-0882.416281, Fax: +39-0882.410271. ·Clin Chem Lab Med · Pubmed #29630505.

ABSTRACT: Gastrointestinal cancers account for around 40% of cancer-related deaths worldwide, representing a global health burden. There is a growing body of evidence highlighting the link between microbiota and gastrointestinal tumorigenesis and/or resistance to therapy. In the present manuscript, we reviewed the published studies on the relationship between the microbiota and the different gastrointestinal tumors, namely, gastric, colorectal and esophageal, including also the cancer of accessory organs such as liver and pancreas. There is an emergent interest in the manipulation of gastrointestinal microflora in order to understand the gastrointestinal tumorigenesis' processes and the establishment of chemoresistance mechanisms.

2 Review Neoadjuvant/preoperative gemcitabine for patients with localized pancreatic cancer: a meta-analysis of prospective studies. 2012

Andriulli, Angelo / Festa, Virginia / Botteri, Edoardo / Valvano, Maria R / Koch, Maurizio / Bassi, Claudio / Maisonneuve, Patrick / Sebastiano, Pierluigi Di. ·Division of Gastroenterology, "Casa Sollievo della Sofferenza" Hospital, IRCCS, San Giovanni Rotondo, Italy. ·Ann Surg Oncol · Pubmed #22012027.

ABSTRACT: BACKGROUND: Long-term prognosis for localized pancreatic cancer remains poor. We sought to assess the benefit of neoadjuvant/preoperative chemotherapy with or without radiotherapy. METHODS: Prospective studies where gemcitabine with or without radiotherapy was provided before surgery in patients with initially resectable or unresectable disease were reviewed by meta-analysis. Primary outcome was survival, and secondary outcomes were tumor response after therapy, toxicity, surgical exploration, and resection rates. RESULTS: Twenty independent studies with 707 participants were included, 366 with resectable lesions and 341 with unresectable lesions. Seven studies were phase I/II trials, 10 phase II, and 3 prospective cohort studies. Estimated 1- and 2-year survival probabilities after resection were 91.7% (95% confidence interval [CI] 75-100) and 67.2% (95% CI 38-87) for initially resectable patients, and 86.3% (95% CI 78-100) and 54.2% (95% CI 25-100) for initially unresectable patients. The complete/partial response rate was 12% (95% CI 4-23) and 27% (95% CI 18-38) in resectable and unresectable lesions, respectively. The rate of treatment-related grade 3-4 toxicity was 31% (95% CI 21-42). Of resectable patients evaluable after restaging, 91% (95% CI 83-97) underwent surgery, and 82% (95% CI 65-95) of explored patients underwent resection. R0 resections amounted to 89% (95% CI 83-94). Of unresectable patients evaluable after restaging, 39% (95% CI 28-50) underwent surgery, and 68% (95% CI 53-82) of explored patients were resected, with 60% (95% CI 50-71) R0 resections. CONCLUSIONS: Current analysis provides marginal support to the assumed benefits of neoadjuvant therapies for patients with resectable cancer, and indicates a potential advantage only for a minority of those with unresectable lesions.

3 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

4 Article Droplet digital PCR quantification of miR-1290 as a circulating biomarker for pancreatic cancer. 2018

Tavano, Francesca / Gioffreda, Domenica / Valvano, Maria R / Palmieri, Orazio / Tardio, Matteo / Latiano, Tiziana P / Piepoli, Ada / Maiello, Evaristo / Pirozzi, Felice / Andriulli, Angelo. ·Division of Gastroenterology and Research Laboratory, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), 71013, Italy. f.tavano@operapadrepio.it. · Division of Gastroenterology and Research Laboratory, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), 71013, Italy. · Department of Surgery, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), 71013, Italy. · Department of Oncology, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), 71013, Italy. ·Sci Rep · Pubmed #30401891.

ABSTRACT: Droplet digital PCR was used to validate miR-1290 as circulating biomarker for pancreatic cancer (PC). The diagnostic performance of miR-1290 was evaluate in 167 PC patients and 267 healthy subjects at clinical risk of developing the disease (HS). MiR-1290 plasma levels were compared to CA 19-9 determinations, and the combination of the two biomarkers was also taken into account. Plasma levels of miR-1290 were higher in PC patients compared to HS (p = 2.55 × 10

5 Article Influence of gemcitabine chemotherapy on the microbiota of pancreatic cancer xenografted mice. 2018

Panebianco, Concetta / Adamberg, Kaarel / Jaagura, Madis / Copetti, Massimiliano / Fontana, Andrea / Adamberg, Signe / Kolk, Kaia / Vilu, Raivo / Andriulli, Angelo / Pazienza, Valerio. ·Gastroenterology Unit, I.R.C.C.S. "Casa Sollievo della Sofferenza" Hospital, viale dei Cappuccini n.1, 71013, San Giovanni Rotondo, FG, Italy. · Department of Chemistry and Biotechnology, Tallinn University of Technology, Tallinn, Estonia. · Center of Food and Fermentation Technologies, University of Tallinn, Tallinn, Estonia. · Biostatistics Unit, I.R.C.C.S. "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo, FG, Italy. · Gastroenterology Unit, I.R.C.C.S. "Casa Sollievo della Sofferenza" Hospital, viale dei Cappuccini n.1, 71013, San Giovanni Rotondo, FG, Italy. pazienza_valerio@yahoo.it. ·Cancer Chemother Pharmacol · Pubmed #29473096.

ABSTRACT: BACKGROUND AND AIMS: Pancreatic ductal adenocarcinoma (PDAC) represents the fourth cause of cancer-related death. We aimed to evaluate whether gemcitabine treatment shapes the gut microbiota in a model of PDAC xenografted mice. MATERIALS AND METHODS: Pancreatic cancer xenograft mice were subjected to gemcitabine injection once per week for 3 weeks to assess the tumor volume as compared to control mice injected with normal saline solution. The composition of fecal microbiota, the activation of NF-kB pathway in cancer tissues and the serum metabolomics were further analyzed. RESULTS: Gemcitabine considerably decreases the proportion of Gram- positive Firmicutes (from about 39 to 17%) and the Gram- negative Bacteroidetes (from 38 to 17%) which are the two dominant phyla in the gut of tumor-bearing control mice. This downshift was replaced by an increase of Proteobacteria (Escherichia coli and Aeromonas hydrophila) from 15 up to 32% and Verrucomicrobia (Akkermansia muciniphila) from 5 to 33% in the gut of drug-receiving mice. An overall increase in inflammation-associated bacteria was observed upon gemcitabine. Consistently, activation of the NF-kB canonical pathway was found in cancer tissues from gemcitabine-treated mice. Serum metabolomics revealed a significant decrease of the purine compounds inosine and xanthine, and a decreasing trend for their metabolically-related molecule hypoxanthine. DISCUSSION: Understanding chemotherapy side effects may explain the lack of activity or the chemoresistant processes and it may help to set up strategies to improve the effectiveness of therapy.

6 Article Common genetic variants associated with pancreatic adenocarcinoma may also modify risk of pancreatic neuroendocrine neoplasms. 2018

Obazee, Ofure / Capurso, Gabriele / Tavano, Francesca / Archibugi, Livia / De Bonis, Antonio / Greenhalf, William / Key, Tim / Pasquali, Claudio / Milanetto, Anna Caterina / Hackert, Thilo / Fogar, Paola / Liço, Valbona / Dervenis, Christos / Lawlor, Rita T / Landoni, Luca / Gazouli, Maria / Zambon, Carlo Federico / Funel, Niccola / Strobel, Oliver / Jamroziak, Krzysztof / Cantù, Cinzia / Malecka-Panas, Ewa / Landi, Stefano / Neoptolemos, John P / Basso, Daniela / Talar-Wojnarowska, Renata / Rinzivillo, Maria / Andriulli, Angelo / Canzian, Federico / Campa, Daniele. ·Digestive and Liver Disease Unit, S. Andrea Hospital, 'Sapienza' University of Rome, Rome, Italy. · Division of Gastroenterology and Research Laboratory, San Giovanni Rotondo, Italy. · Department of Surgery, IRCCS Scientific Institute and Regional General Hospital "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy. · Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, UK. · Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK. · Pancreatic and Digestive Endocrine Surgery - Department of Surgery, Oncology and Gastroenterology -DiSCOG, University of Padova, Padova, Italy. · Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Im Neuenheimer Feld, Heidelberg, Germany. · Department of Laboratory Medicine, University Hospital of Padova, Padova, Italy. · Department of Surgical Oncology and Hepatobiliary Surgery, Metropolitan General Hospital, Pireas, Greece. · ARC-NET Center for Applied Research on Cancer, University and Hospital Trust of Verona, Verona, Italy. · Department of Surgery, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy. · Department of Basic Medical Sciences, Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. · Department of Medicine - DIMED, University of Padova, Padova, Italy. · Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy. · Department of Hematology, Medical University of Lodz, Lodz, Poland. · Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland. · Department of Biology, University of Pisa, Pisa, Italy. · Genomic Epidemiology Group, German Cancer Research Centre (DKFZ), Heidelberg, Germany ·Carcinogenesis · Pubmed #29309705.

ABSTRACT: Pancreatic neuroendocrine neoplasms (pNEN) account for less than 5% of all pancreatic neoplasms and genetic association studies on susceptibility to the disease are limited. We sought to identify possible overlap of genetic susceptibility loci between pancreatic ductal adenocarcinoma (PDAC) and pNEN; therefore, PDAC susceptibility variants (n = 23) from Caucasian genome-wide association studies (GWAS) were genotyped in 369 pNEN cases and 3277 controls from the PANcreatic Disease ReseArch (PANDoRA) consortium to evaluate the odds associated with pNEN risk, disease onset and tumor characteristics. Main effect analyses showed four PDAC susceptibility variants-rs9854771, rs1561927, rs9543325 and rs10919791 to be associated with pNEN risk. Subsequently, only associations with rs9543325, rs10919791 and rs1561927 were noteworthy with false positive report probability (FPRP) tests. Stratified analyses considering age at onset (50-year threshold), showed rs2736098, rs16986825 and rs9854771 to be associated with risk of developing pNEN at a younger age. Stratified analyses also showed some single nucleotide polymorphisms to be associated with different degrees of tumor grade, metastatic potential and functionality. Our results identify known GWAS PDAC susceptibility loci, which may also be involved in sporadic pNEN etiology and suggest that some genetic mechanisms governing pathogenesis of these two entities may be similar, with few of these loci being more influential in younger cases or tumor subtypes.

7 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

8 Article Functional single nucleotide polymorphisms within the cyclin-dependent kinase inhibitor 2A/2B region affect pancreatic cancer risk. 2016

Campa, Daniele / Pastore, Manuela / Gentiluomo, Manuel / Talar-Wojnarowska, Renata / Kupcinskas, Juozas / Malecka-Panas, Ewa / Neoptolemos, John P / Niesen, Willem / Vodicka, Pavel / Delle Fave, Gianfranco / Bueno-de-Mesquita, H Bas / Gazouli, Maria / Pacetti, Paola / Di Leo, Milena / Ito, Hidemi / Klüter, Harald / Soucek, Pavel / Corbo, Vincenzo / Yamao, Kenji / Hosono, Satoyo / Kaaks, Rudolf / Vashist, Yogesh / Gioffreda, Domenica / Strobel, Oliver / Shimizu, Yasuhiro / Dijk, Frederike / Andriulli, Angelo / Ivanauskas, Audrius / Bugert, Peter / Tavano, Francesca / Vodickova, Ludmila / Zambon, Carlo Federico / Lovecek, Martin / Landi, Stefano / Key, Timothy J / Boggi, Ugo / Pezzilli, Raffaele / Jamroziak, Krzysztof / Mohelnikova-Duchonova, Beatrice / Mambrini, Andrea / Bambi, Franco / Busch, Olivier / Pazienza, Valerio / Valente, Roberto / Theodoropoulos, George E / Hackert, Thilo / Capurso, Gabriele / Cavestro, Giulia Martina / Pasquali, Claudio / Basso, Daniela / Sperti, Cosimo / Matsuo, Keitaro / Büchler, Markus / Khaw, Kay-Tee / Izbicki, Jakob / Costello, Eithne / Katzke, Verena / Michalski, Christoph / Stepien, Anna / Rizzato, Cosmeri / Canzian, Federico. ·Department of Biology, University of Pisa, Pisa, Italy. · Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland. · Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania. · Institute for Health Research Liverpool Pancreas Biomedical Research Unit, University of Liverpool, Liverpool, United Kingdom. · Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany. · Institute of Experimental Medicine, Czech Academy of Science, Prague, Czech Republic. · Institute of Biology and Medical Genetics, 1st Medical Faculty, Charles University, Prague, Czech Republic. · Digestive and Liver Disease Unit, S. Andrea Hospital, 'Sapienza' University of Rome, Rome, Italy. · Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. · Department of Epidemiology and Biostatistics, The 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 Basic Medical Sciences, Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, Athens, Greece. · Oncological Department Massa Carrara Azienda USL Toscana Nord Ovest, Carrara, Italy. · Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy. · Division Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan. · Institute of Transfusion Medicine and Immunology, German Red Cross Blood Service Baden-Württemberg - Hessen gGmbH, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. · Laboratory of Toxicogenomics, National Institute of Public Health, Prague, Czech Republic. · Laboratory of Pharmacogenomics, Biomedical Center, Faculty of Medicine in Pilsen, Charles University in Prague, Pilsen, Czech Republic. · ARC-Net Research Centre, and Department of Diagnostics and Public Health University and Hospital Trust of Verona, Verona, Italy. · Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan. · Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. · Division of Gastroenterology and Research Laboratory, IRCCS Scientific Institute and Regional General Hospital "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy. · Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Nagoya, Japan. · Department of Pathology, Academic Medical Centre, Amsterdam, The Netherlands. · Biomedical Center, Faculty of Medicine in Pilsen, Charles University in Prague, Prague, Czech Republic. · Department of Medicine - DIMED, University of Padova, Padova, Italy. · Department of Surgery I, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic. · Epidemiology Unit Nuffield Department of Population Health University of Oxford, Oxford, UK. · Division of General and Transplant Surgery, Pisa University Hospital, Pisa, Italy. · Pancreas Unit, Department of Digestive System, Dant'Orsola-Malpighi Hospital, Bologna, Italy. · Department of Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland. · Department of Oncology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic. · Blood Transfusion Service, Azienda Ospedaliero Universitaria Meyer, Florence, Italy. · Department of Surgery, Academic Medical Centre, Amsterdam, The Netherlands. · Colorectal Unit, First Department of Propaedeutic Surgery, Athens Medical School, National and Kapodistrian University of Athens, Athens, Greece. · Department of Surgery, Oncology and Gastroenterology-DiSCOG, University of Padova, Padova, Italy. · Department of Laboratory Medicine, University-Hospital of Padova, Padova, Italy. · Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan. · Clinical Gerontology Unit, Addenbrooke’s Hospital, School of Clinical Medicine, University of Cambridge, Cambridge, UK. · Laboratory of Clinical, Transplant Immunology and Genetics, Copernicus Memorial Hospital, Lodz, Poland. · Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy. ·Oncotarget · Pubmed #27486979.

ABSTRACT: The CDKN2A (p16) gene plays a key role in pancreatic cancer etiology. It is one of the most commonly somatically mutated genes in pancreatic cancer, rare germline mutations have been found to be associated with increased risk of developing familiar pancreatic cancer and CDKN2A promoter hyper-methylation has been suggested to play a critical role both in pancreatic cancer onset and prognosis. In addition several unrelated SNPs in the 9p21.3 region, that includes the CDNK2A, CDNK2B and the CDNK2B-AS1 genes, are associated with the development of cancer in various organs. However, association between the common genetic variability in this region and pancreatic cancer risk is not clearly understood. We sought to fill this gap in a case-control study genotyping 13 single nucleotide polymorphisms (SNPs) in 2,857 pancreatic ductal adenocarcinoma (PDAC) patients and 6,111 controls in the context of the Pancreatic Disease Research (PANDoRA) consortium. We found that the A allele of the rs3217992 SNP was associated with an increased pancreatic cancer risk (ORhet=1.14, 95% CI 1.01-1.27, p=0.026, ORhom=1.30, 95% CI 1.12-1.51, p=0.00049). This pleiotropic variant is reported to be a mir-SNP that, by changing the binding site of one or more miRNAs, could influence the normal cell cycle progression and in turn increase PDAC risk. In conclusion, we observed a novel association in a pleiotropic region that has been found to be of key relevance in the susceptibility to various types of cancer and diabetes suggesting that the CDKN2A/B locus could represent a genetic link between diabetes and pancreatic cancer risk.

9 Article Support Vector Machine Based on microRNA Expression Profiles to Predict Histological Origin of Ampullary Carcinoma: Case Report of a Patient Affected From Adenocarcinoma of the Papilla of Vater With Lynch Syndrome. 2016

Tavano, Francesca / Copetti, Massimiliano / Piepoli, Ada / Carella, Massimo / Gentile, Annamaria / Burbaci, Francesca Paola / Fontana, Andrea / De Bonis, Antonio / di Mola, Fabio Francesco / di Sebastiano, Pierluigi / Andriulli, Angelo. ·From the *Division of Gastroenterology and Research Laboratory, †Unit of Biostatistics, ‡Unit of Medical Genetics, §Department of Surgery, IRCCS "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo (FG); and ∥Division of Surgical Oncology, "SS Annunziata" Hospital, Chieti, Italy. ·Pancreas · Pubmed #26954494.

ABSTRACT: Adenocarcinomas of Vater's papilla (PVAC) may originate from either the pancreatic duct or the intestinal epithelium. Conflicting data have been reported about the frequency of the 2 anatomical entities and their influence on patients' prognosis. To ascertain the anatomical origin of PVAC in a family member of a Lynch syndrome kindred, we searched for microRNA (miRNA) expression profiles on resected tumor specimens. The support vector machine was trained on our previous miRNAs expression data sets of pancreatic and colorectal tissue samples and used to classify the site of origin of the tumor in our patient. The support vector machine worked by contrasting the profiles of miRNAs in patients with pancreatic ductal and colorectal cancers to that of our patient, which was finally classified as pancreatic ductal adenocarcinoma accordingly to alterations of 55 miRNAs. The PVAC might be originated from ductal epithelium rather than from the intestinal mucosa of the papilla in the case at issue. Alteration of miR-548b-3p, miR-551a, miR-21, miR-92a, miR-let-7i, and miR-181a* emerged as potentially associated with cancer genetic susceptibility in PVAC.

10 Article Development of a metabolites risk score for one-year mortality risk prediction in pancreatic adenocarcinoma patients. 2016

Fontana, Andrea / Copetti, Massimiliano / Di Gangi, Iole Maria / Mazza, Tommaso / Tavano, Francesca / Gioffreda, Domenica / Mattivi, Fulvio / Andriulli, Angelo / Vrhovsek, Urska / Pazienza, Valerio. ·Unit of Biostatistics I.R.C.C.S. "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo (FG), Italy. · Department of Food Quality and Nutrition, Research and Innovation Centre, Fondazione Edmund Mach (FEM), San Michele all'Adige, Italy. · Unit of Bioinformatics, I.R.C.C.S. "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo (FG), Italy. · Gastroenterology Unit, I.R.C.C.S. "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo (FG), Italy. ·Oncotarget · Pubmed #26840268.

ABSTRACT: PURPOSE: Survival among patients with adenocarcinoma pancreatic cancer (PDCA) is highly variable, which ranges from 0% to 20% at 5 years. Such a wide range is due to tumor size and stage, as well other patients' characteristics. We analyzed alterations in the metabolomic profile, of PDCA patients, which are potentially predictive of patient's one-year mortality. EXPERIMENTAL DESIGN: A targeted metabolomic assay was conducted on serum samples of patients diagnosed with pancreatic cancer. Statistical analyses were performed only for those 27 patients with information on vital status at follow-up and baseline clinical features. Random Forest analysis was performed to identify all metabolites and clinical variables with the best capability to predict patient's mortality risk at one year. Regression coefficients were estimated from multivariable Weibull survival model, which included the most associated metabolites. Such coefficients were used as weights to build a metabolite risk score (MRS) which ranged from 0 (lowest mortality risk) to 1 (highest mortality risk). The stability of these weights were evaluated performing 10,000 bootstrap resamplings. RESULTS: MRS was built as a weighted linear combination of the following five metabolites: Valine (HR = 0.62, 95%CI: 0.11-1.71 for each standard deviation (SD) of 98.57), Sphingomyeline C24:1 (HR = 2.66, 95%CI: 1.30-21.09, for each SD of 20.67), Lysine (HR = 0.36, 95%CI: 0.03-0.77, for each SD of 51.73), Tripentadecanoate TG15 (HR = 0.25, 95%CI: 0.01-0.82, for each SD of 2.88) and Symmetric dimethylarginine (HR = 2.24, 95%CI: 1.28-103.08, for each SD of 0.62), achieving a very high discrimination ability (survival c-statistic of 0.855, 95%CI: 0.816-0.894). Such association was still present even after adjusting for the most associated clinical variables (confounders). CONCLUSIONS: The mass spectrometry-based metabolomic profiling of serum represents a valid tool for discovering novel candidate biomarkers with prognostic ability to predict one-year mortality risk in patients with pancreatic adenocarcinoma.

11 Article Metabolomic profile in pancreatic cancer patients: a consensus-based approach to identify highly discriminating metabolites. 2016

Di Gangi, Iole Maria / Mazza, Tommaso / Fontana, Andrea / Copetti, Massimiliano / Fusilli, Caterina / Ippolito, Antonio / Mattivi, Fulvio / Latiano, Anna / Andriulli, Angelo / Vrhovsek, Urska / Pazienza, Valerio. ·Department of Food Quality and Nutrition, Research and Innovation Centre, Fondazione Edmund Mach (FEM), San Michele all'Adige, TN, Italy. · Unit of Bioinformatics, I.R.C.C.S. "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo, FG, Italy. · Unit of Biostatistics I.R.C.C.S. "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo, FG, Italy. · Gastroenterology Unit, I.R.C.C.S. "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo, FG, Italy. ·Oncotarget · Pubmed #26735340.

ABSTRACT: PURPOSE: pancreatic adenocarcinoma is the fourth leading cause of cancer related deaths due to its aggressive behavior and poor clinical outcome. There is a considerable variability in the frequency of serum tumor markers in cancer' patients. We performed a metabolomics screening in patients diagnosed with pancreatic cancer. EXPERIMENTAL DESIGN: Two targeted metabolomic assays were conducted on 40 serum samples of patients diagnosed with pancreatic cancer and 40 healthy controls. Multivariate methods and classification trees were performed. MATERIALS AND METHODS: Sparse partial least squares discriminant analysis (SPLS-DA) was used to reduce the high dimensionality of a pancreatic cancer metabolomic dataset, differentiating between pancreatic cancer (PC) patients and healthy subjects. Using Random Forest analysis palmitic acid, 1,2-dioleoyl-sn-glycero-3-phospho-rac-glycerol, lanosterol, lignoceric acid, 1-monooleoyl-rac-glycerol, cholesterol 5α,6α epoxide, erucic acid and taurolithocholic acid (T-LCA), oleoyl-L-carnitine, oleanolic acid were identified among 206 metabolites as highly discriminating between disease states. Comparison between Receiver Operating Characteristic (ROC) curves for palmitic acid and CA 19-9 showed that the area under the ROC curve (AUC) of palmitic acid (AUC=1.000; 95% confidence interval) is significantly higher than CA 19-9 (AUC=0.963; 95% confidence interval: 0.896-1.000). CONCLUSION: Mass spectrometry-based metabolomic profiling of sera from pancreatic cancer patients and normal subjects showed significant alterations in the profiles of the metabolome of PC patients as compared to controls. These findings offer an information-rich matrix for discovering novel candidate biomarkers with diagnostic or prognostic potentials.

12 Article SIRT1 and circadian gene expression in pancreatic ductal adenocarcinoma: Effect of starvation. 2015

Tavano, Francesca / Pazienza, Valerio / Fontana, Andrea / Burbaci, Francesca Paola / Panebianco, Concita / Saracino, Chiara / Lombardi, Lucia / De Bonis, Antonio / di Mola, Fabio Francesco / di Sebastiano, Pierluigi / Piepoli, Ada / Vinciguerra, Manlio / Fracavilla, Massimo / Giuliani, Francesco / Rubino, Rosa / Andriulli, Angelo / Mazzoccoli, Gianluigi. ·Division of Gastroenterology, IRCCS Scientific Institute and Regional General Hospital "Casa Sollievo della Sofferenza" , San Giovanni Rotondo (FG) , Italy . ·Chronobiol Int · Pubmed #25798752.

ABSTRACT: Pancreatic cancer (PC), the fourth leading cause of cancer-related deaths, is characterized by high aggressiveness and resistance to chemotherapy. Pancreatic carcinogenesis is kept going by derangement of essential cell processes, such as proliferation, apoptosis, metabolism and autophagy, characterized by rhythmic variations with 24-h periodicity driven by the biological clock. We assessed the expression of the circadian genes ARNLT, ARNLT2, CLOCK, PER1, PER2, PER3, CRY1, CRY2 and the starvation-activated histone/protein deacetylase SIRT1 in 34 matched tumor and non-tumor tissue specimens of PC patients, and evaluated in PC derived cell lines if the modulation of SIRT1 expression through starvation could influence the temporal pattern of expression of the circadian genes. We found a significant down-regulation of ARNLT (p = 0.015), CRY1 (p = 0.013), CRY2 (p = 0.001), PER1 (p < 0.0001), PER2 (p < 0.001), PER3 (p = 0.001) and SIRT1 (p = 0.017) in PC specimens. PER3 and CRY2 expression levels were lower in patients with jaundice at diagnosis ( < 0.05). Having adjusted for age, adjuvant therapy and tumor stage, we evidenced that patients with higher PER2 and lower SIRT1 expression levels showed lower mortality (p = 0.028). Levels and temporal patterns of expression of many circadian genes and SIRT1 significantly changed upon serum starvation in vitro, with differences among four different PC cell lines examined (BXPC3, CFPAC, MIA-PaCa-2 and PANC-1). Serum deprivation induced changes of the overall mean level of the wave and amplitude, lengthened or shortened the cycle time and phase-advanced or phase-delayed the rhythmic oscillation depending on the gene and the PC cell line examined. In conclusion, a severe deregulation of expression of SIRT1 and circadian genes was evidenced in the cancer specimens of PC patients, and starvation influenced gene expression in PC cell lines, suggesting that the altered interplay between SIRT1 and the core circadian proteins could represent a crucial player in the process of pancreatic carcinogenesis.

13 Article Modeling interactions between Human Equilibrative Nucleoside Transporter-1 and other factors involved in the response to gemcitabine treatment to predict clinical outcomes in pancreatic ductal adenocarcinoma patients. 2014

Tavano, Francesca / Fontana, Andrea / Pellegrini, Fabio / Burbaci, Francesca Paola / Rappa, Francesca / Cappello, Francesco / Copetti, Massimiliano / Maiello, Evaristo / Lombardi, Lucia / Graziano, Paolo / Vinciguerra, Manlio / di Mola, Fabio Francesco / di Sebastiano, Pierluigi / Andriulli, Angelo / Pazienza, Valerio. · ·J Transl Med · Pubmed #25199538.

ABSTRACT: BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive malignancy, characterized by largely unsatisfactory responses to the currently available therapeutic strategies. In this study we evaluated the expression of genes involved in gemcitabine uptake in a selected cohort of patients with PDAC, with well-defined clinical-pathological features. METHODS: mRNA levels of hENT1, CHOP, MRP1 and DCK were evaluated by means of qRT-PCR in matched pairs of tumor and adjacent normal tissue samples collected from PDAC patients treated with gemcitabine after surgical tumor resection. To detect possible interaction between gene expression levels and to identify subgroups of patients at different mortality/progression risk, the RECursive Partitioning and Amalgamation (RECPAM) method was used. RESULTS: RECPAM analysis showed that DCK and CHOP were most relevant variables for the identification of patients with different mortality risk, while hENT1 and CHOP were able to identify subgroups of patients with different disease progression risk. CONCLUSION: hENT1, CHOP, MRP1 and DCK appear correlated to PDAC, and this interaction might influence disease behavior.

14 Article Influence of preoperative biliary drainage on surgical outcome after pancreaticoduodenectomy: single centre experience. 2014

di Mola, F Francesco / Tavano, Francesca / Rago, R Rita / De Bonis, Antonio / Valvano, M Rosa / Andriulli, Angelo / di Sebastiano, Pierluigi. ·Division of Surgical Oncology, "SS Annunziata" Hospital, 66100, Chieti, Italy. ·Langenbecks Arch Surg · Pubmed #24682374.

ABSTRACT: PURPOSE: Controversy prevails on the impact of preoperative biliary drainage (PBD) on postoperative complications and clinical outcome of pancreatic cancer. We determined whether PBD is associated with increased morbidity and mortality rates after pancreaticoduodenectomy. METHODS: A total of 131 consecutive patients who underwent pancreaticoduodenectomy (93 jaundiced, 38 with no jaundice) were included in this study. Overall, 57 % of jaundiced patients underwent PBD, while 43 % were not drained. The impact of PBD on postoperative morbidity and mortality was evaluated by means of logistic regression analysis. The Kaplan-Meier method was applied to determine the effect of PBD on survival of patients with malignant lesions. RESULTS: Mortality and morbidity rate was 3 % and 54.6 %, respectively. PBD was demonstrated to be the unique predictor of complications (odds ration [OR] = 10.18; 95 % confidence interval [CI], 3.65-28.39, p < 0.001). The jaundiced patients who were drained exhibited high frequencies of wound infection (p < 0.001), post-pancreatectomy haemorrhage (p = 0.0185) and hyperglycaemia (p < 0.001). In addition, an increased frequency of pancreatic fistula emerged among drained patients compared to those who were not drained (p = 0.036). PBD did not affect survival of patient with malignant lesions. CONCLUSIONS: With the exception of the classical indications, PBD should be carefully evaluated in patients with resectable pancreatic cancer.

15 Article Neoadjuvant chemo-radiotherapy for patients with borderline resectable pancreatic cancer: a meta-analytical evaluation of prospective studies. 2013

Festa, Virginia / Andriulli, Angelo / Valvano, Maria Rosaria / Uomo, Generoso / Perri, Francesco / Andriulli, Nicola / Corrao, Salvatore / Koch, Maurizio. ·Division of Gastroenterology, "San Filippo Neri" Hospital. Rome, Italy. v.festa@sanfilipponeri.roma.it. ·JOP · Pubmed #24216547.

ABSTRACT: CONTEXT: For patients with borderline resectable pancreatic cancer, the benefit of neoadjuvant therapy remains to be defined. OBJECTIVE: We did a systematic search of the literature on this topic. METHODS: Prospective studies where chemotherapy with or without radiotherapy was given before surgery to patients with borderline resectable cancer, were analyzed by a meta-analytical approach. MAIN OUTCOME MEASURES: Primary outcome was surgical exploration and resection rates; tumor response, therapy-induced toxicity, and survival were secondary outcomes. Data were expressed as weighted pooled proportions with 95% confidence intervals (95% CI). RESULTS: Ten studies with 182 participants were included. Following treatment, 69% of patients (95% CI: 56-80%) were brought to surgery and 80% (95% CI: 66-90%) of surgically-explored patients were resected. Eighty-three percent (95% CI: 74-90%) of resected specimens were deemed R0 resections. The weighted fractions of resected patients alive at 1 and 2 years were 61% (95% CI: 48-100%) and 44% (95% CI: 32-59%), respectively. At restaging following neoadjuvant therapy, weighted frequencies for complete/partial response were 16% (95% CI: 9-28%), 69% (95% CI: 60-76%) for stable disease, and 19% (95% CI: 13-25%) for progressive cancer. Treatment-related grade 3-4 toxicity was 32% (95% CI: 21-45%). CONCLUSION: This meta-analysis shows that downstaging of the lesion following neoadjuvant therapies is uncommon for patients with borderline resectable pancreatic cancer. A clear benefit of this regimen could be to spare surgery to patients with progressive disease during the frame-time chemo-radiotherapy is being delivered.

16 Article Cancer risk associated with STK11/LKB1 germline mutations in Peutz-Jeghers syndrome patients: results of an Italian multicenter study. 2013

Resta, Nicoletta / Pierannunzio, Daniela / Lenato, Gennaro Mariano / Stella, Alessandro / Capocaccia, Riccardo / Bagnulo, Rosanna / Lastella, Patrizia / Susca, Francesco Claudio / Bozzao, Cristina / Loconte, Daria Carmela / Sabbà, Carlo / Urso, Emanuele / Sala, Paola / Fornasarig, Mara / Grammatico, Paola / Piepoli, Ada / Host, Cristina / Turchetti, Daniela / Viel, Alessandra / Memo, Luigi / Giunti, Laura / Stigliano, Vittoria / Varesco, Liliana / Bertario, Lucio / Genuardi, Maurizio / Lucci Cordisco, Emanuela / Tibiletti, Maria Grazia / Di Gregorio, Carmela / Andriulli, Angelo / Ponz de Leon, Maurizio / Anonymous3090750. ·Department of Biomedical Sciences and Human Oncology, Medical Genetics Unit, Aldo Moro, University of Bari, Italy. nicoletta.resta@uniba.it ·Dig Liver Dis · Pubmed #23415580.

ABSTRACT: BACKGROUND: Germline mutations in the STK11/LKB1 gene cause Peutz-Jeghers syndrome, an autosomal-dominantly inherited condition characterized by mucocutaneous pigmentation, hamartomatous gastrointestinal polyposis, and an increased risk for various malignancies. We here report the results of the first Italian collaborative study on Peutz-Jeghers syndrome. AIMS: To assess cancer risks in a large homogenous cohort of patients with Peutz-Jeghers syndrome, carrying, in large majority, an identified STK11/LKB1 mutation. METHODS: One-hundred and nineteen patients with Peutz-Jeghers syndrome, ascertained in sixteen different Italian centres, were enrolled in a retrospective cohort study. Relative and cumulative cancer risks and genotype-phenotype correlations were evaluated. RESULTS: 36 malignant tumours were found in 31/119 (29 STK11/LKB1 mutation carriers) patients. The mean age at first cancer diagnosis was 41 years. The relative overall cancer risk was 15.1 with a significantly higher risk (p < 0.001) in females (22.0) than in males (8.6). Highly increased relative risks were present for gastrointestinal (126.2) and gynaecological cancers (27.7), in particular for pancreatic (139.7) and cervical cancer (55.6). The Kaplan-Meier estimates for overall cumulative cancer risks were 20%, 43%, 71%, and 89%, at age 40, 50, 60 and 65 years, respectively. CONCLUSION: Peutz-Jeghers syndrome entails markedly elevated cancer risks, mainly for pancreatic and cervical cancers. This study provides a helpful reference for improving current surveillance protocols.

17 Article Genetic susceptibility to pancreatic cancer and its functional characterisation: the PANcreatic Disease ReseArch (PANDoRA) consortium. 2013

Campa, Daniele / Rizzato, Cosmeri / Capurso, Gabriele / Giese, Nathalia / Funel, Niccola / Greenhalf, William / Soucek, Pavel / Gazouli, Maria / Pezzilli, Raffaele / Pasquali, Claudio / Talar-Wojnarowska, Renata / Cantore, Maurizio / Andriulli, Angelo / Scarpa, Aldo / Jamroziak, Krzysztof / Delle Fave, Gianfranco / Costello, Eithne / Khaw, Kay-Tee / Heller, Anette / Key, Tim J / Theodoropoulos, George / Malecka-Panas, Ewa / Mambrini, Andrea / Bambi, Franco / Landi, Stefano / Pedrazzoli, Sergio / Bassi, Claudio / Pacetti, Paola / Piepoli, Ada / Tavano, Francesca / di Sebastiano, Pierluigi / Vodickova, Ludmila / Basso, Daniela / Plebani, Mario / Fogar, Paola / Büchler, Markus W / Bugert, Peter / Vodicka, Pavel / Boggi, Ugo / Neoptolemos, John P / Werner, Jens / Canzian, Federico. ·German Cancer Research Center (DKFZ), Heidelberg, Germany. d.campa@dkfz.de ·Dig Liver Dis · Pubmed #23206934.

ABSTRACT: Pancreatic cancer is the fourth leading cause of cancer deaths in the European Union and in the USA, but little is known about its genetic susceptibility. The PANcreatic Disease ReseArch (PANDoRA) consortium was established to unite the efforts of different research groups; its aim is to create a large bio-database to uncover new genetic factors for pancreatic cancer risk, response to treatment, and patient survival. So far 2220 cases of pancreatic adenocarcinoma, a smaller number of cases of endocrine pancreatic tumours (n=86), chronic pancreatitis (n=272) and 3847 healthy controls have been collected. As a collective effort of the consortium, SNPs associated with pancreatic adenocarcinoma risk from a genome-wide association study performed in Caucasians were replicated. The possibility that the same genetic polymorphisms may influence patient survival as well was also addressed. This collective effort is particularly important for pancreatic cancer because it is a relatively rare disease for which little is known about aetiopathogenesis and risk factors. The recruitment of additional collaborators and partner institutions is continuously on-going.

18 Article Changes in miR-143 and miR-21 expression and clinicopathological correlations in pancreatic cancers. 2012

Tavano, Francesca / di Mola, Francesco Fabio / Piepoli, Ada / Panza, Anna / Copetti, Massimiliano / Burbaci, Francesca Paola / Latiano, Tiziana / Pellegrini, Fabio / Maiello, Evaristo / Andriulli, Angelo / di Sebastiano, Pierluigi. ·Department of Surgery, Casa Sollievo della Sofferenza Hospital, IRCCS, San Giovanni Rotondo, Italy. ·Pancreas · Pubmed #22836856.

ABSTRACT: OBJECTIVES: Despite advances in clinical management of pancreatic cancer (PC), there is still room for improvement in early detection, diagnosis, and treatment strategies. The role of microRNAs (miRNAs) in tumor biology might pinpoint an alteration in expression of miRNAs as new diagnostic/prognostic biomarkers. METHODS: Expression levels of miR-143 and miR-21 and correlations with clinicopathological features were analyzed in 26 matched pairs of tumor and adjacent noncancerous tissue samples collected from patients with PCs, including 18 pancreatic ductal adenocarcinomas (PDACs) and 8 adenocarcinomas of Vater's papilla (PVACs). RESULTS: Compared to normal tissues, miR-143 was up-regulated in both PDAC and PVAC tumor samples (P = 0.0028 and P = 0.039, respectively). Conversely, alterations in miR-21 expression were significantly different in PDAC versus PVAC samples (P = 0.0049). Tumor levels of miR-21 were associated with preoperative serum levels of CA 19-9 (r = 0.63, P = 0.0022), whereas miR-143 expression was negatively correlated to lymph node spreading (r = -0.64; P = 0.0004). Correlation between miR-143 and miR-21 expression levels in patients with PDAC was observed (r = 0.53, P = 0.023). CONCLUSIONS: Deregulation of miR-143 and miR-21 may reflect histological features and biological behavior of different PCs. Association data with clinical parameters might indicate a prognostic significance for miR-143 and miR-21 in PCs.

19 Article Mirna expression profiles identify drivers in colorectal and pancreatic cancers. 2012

Piepoli, Ada / Tavano, Francesca / Copetti, Massimiliano / Mazza, Tommaso / Palumbo, Orazio / Panza, Anna / di Mola, Francesco Fabio / Pazienza, Valerio / Mazzoccoli, Gianluigi / Biscaglia, Giuseppe / Gentile, Annamaria / Mastrodonato, Nicola / Carella, Massimo / Pellegrini, Fabio / di Sebastiano, Pierluigi / Andriulli, Angelo. ·Department and Laboratory of Gastroenterology, IRCCS Casa Sollievo della Sofferenza, Research Hospital, San Giovanni Rotondo, Italy. a.piepoli@operapadrepio.it ·PLoS One · Pubmed #22479426.

ABSTRACT: BACKGROUND AND AIM: Altered expression of microRNAs (miRNAs) hallmarks many cancer types. The study of the associations of miRNA expression profile and cancer phenotype could help identify the links between deregulation of miRNA expression and oncogenic pathways. METHODS: Expression profiling of 866 human miRNAs in 19 colorectal and 17 pancreatic cancers and in matched adjacent normal tissues was investigated. Classical paired t-test and random forest analyses were applied to identify miRNAs associated with tissue-specific tumors. Network analysis based on a computational approach to mine associations between cancer types and miRNAs was performed. RESULTS: The merge between the two statistical methods used to intersect the miRNAs differentially expressed in colon and pancreatic cancers allowed the identification of cancer-specific miRNA alterations. By miRNA-network analysis, tissue-specific patterns of miRNA deregulation were traced: the driving miRNAs were miR-195, miR-1280, miR-140-3p and miR-1246 in colorectal tumors, and miR-103, miR-23a and miR-15b in pancreatic cancers. CONCLUSION: MiRNA expression profiles may identify cancer-specific signatures and potentially useful biomarkers for the diagnosis of tissue specific cancers. miRNA-network analysis help identify altered miRNA regulatory networks that could play a role in tumor pathogenesis.

20 Article A modified fast-track program for pancreatic surgery: a prospective single-center experience. 2011

di Sebastiano, Pierluigi / Festa, Leonardina / De Bonis, Antonio / Ciuffreda, Andrea / Valvano, Maria Rosa / Andriulli, Angelo / di Mola, F Francesco. ·Department of Surgery, IRCCS-Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy. p.disebastiano@operapadrepio.it ·Langenbecks Arch Surg · Pubmed #20703500.

ABSTRACT: OBJECTIVE: The objective of this study is to evaluate the impact of a fast-track protocol in a high-volume center for patients with pancreatic disorders. BACKGROUND: The concept of fast-track surgery allowing accelerated postoperative recovery is accepted in colorectal surgery, but efficacy data are only preliminary for patients undergoing major pancreatic surgery. We aimed to evaluate the impact of a modified fast-track protocol in a high-volume center for patients with pancreatic disorders. METHODS: Between February 2005 and January 2010, 145 subjects had resective pancreatic surgery and were enrolled in the program. Essential features of the program were no preanaesthetic medication, upper and lower air-warming device, avoidance of excessive i.v. fluids perioperatively, effective control of pain, early reinstitution of oral feeding, and immediate mobilization and restoration of bowel function following surgery. Outcome measures were postoperative complications such as pancreatic fistula, delayed gastric emptying, biliary leak, intra-abdominal abscess, post-pancreatectomy hemorrhage, acute pancreatitis, wound infection, 30-day mortality, postoperative hospital stay, and readmission rates. RESULTS: On average, patients were discharged on postoperative day 10 (range 6-69), with a 30-day readmission rate of 6.2%. Percentage of patients with at least one complication was 38.6%. Pancreatic anastomotic leakage occurred in seven of 101 pancreatico-jejunostomies, and biliary leak in three of 109 biliary jejunostomies. Postoperative hemorrhage occurred in ten (6.9%) patients and wound infection in nine (6.2%) cases. In-hospital mortality was 2.7%. Fast-track parameters, such as normal food and first stool, correlated significantly with early discharge (<0.05). At multivariate analysis, lack of jaundice, and resumption of normal diet by the 5th postoperative day were independent factors of early discharge. CONCLUSION: Fast-track programs are feasible, easy, and also applicable for patients undergoing a major surgery such as pancreatic resection.