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Pancreatic Neoplasms: HELP
Articles by Ugo Boggi
Based on 45 articles published since 2010
(Why 45 articles?)
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Between 2010 and 2020, U. Boggi wrote the following 45 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Review Robotic pancreatoduodenectomy with vascular resection. 2016

Kauffmann, Emanuele F / Napoli, Niccolò / Menonna, Francesca / Vistoli, Fabio / Amorese, Gabriella / Campani, Daniela / Pollina, Luca Emanuele / Funel, Niccola / Cappelli, Carla / Caramella, Davide / Boggi, Ugo. ·Division of General and Transplant Surgery, University of Pisa and Azienda Ospedaliero Universitaria Pisana, Via Paradisa 2, 56124, Pisa, Italy. · Division of Anesthesia and Intensive Care, University of Pisa and Azienda Ospedaliero Universitaria Pisana, Pisa, Italy. · Division of Pathology, University of Pisa and Azienda Ospedaliero Universitaria Pisana, Pisa, Italy. · Division of Radiology, University of Pisa and Azienda Ospedaliero Universitaria Pisana, Pisa, Italy. · Division of General and Transplant Surgery, University of Pisa and Azienda Ospedaliero Universitaria Pisana, Via Paradisa 2, 56124, Pisa, Italy. u.boggi@med.unipi.it. ·Langenbecks Arch Surg · Pubmed #27553112.

ABSTRACT: PURPOSE: This study aims to define the current status of robotic pancreatoduodenectomy (RPD) with resection and reconstruction of the superior mesenteric/portal vein (RPD-SMV/PV). METHODS: Our experience on RPD, including RPD-SMV/PV, is presented along with a description of the surgical technique and a systematic review of the literature on RPD-SMV/PV. RESULTS: We have performed 116 RPD and 14 RPD-SMV/PV. Seven additional cases of RPD-SMV/PV were identified in the literature. In our experience, RPD and RPD-SMV/PV were similar in all baseline variables, but lower mean body mass and higher prevalence of pancreatic cancer in RPD-SMV/PV. Regarding the type of vein resection, there were one type 2 (7.1 %), five type 3 (35.7 %) and eight type 4 (57.2 %) resections. As compared to RPD, RPD-SMV/PV required longer operative time, had higher median estimated blood loss, and blood transfusions were required more frequently. Incidence and severity of post-operative complications were not increased in RPD-SMV/PV, but post-pancreatectomy hemorrhage occurred more frequently after this procedure. In pancreatic cancer, RPD-SMV/PV was associated with a higher mean number of examined lymph nodes (60.0 ± 13.9 vs 44.6 ± 11.0; p = 0.02) and with the same rate of microscopic margin positivity (25.0 % vs 26.1 %). Mean length or resected vein was 23.1 ± 8.08 mm. Actual tumour infiltration was discovered in ten patients (71.4 %), reaching the adventitia in four patients (40.0 %), the media in two patients (20.0 %), and the intima in four patients (40.0 %). Literature review identified seven additional cases, all reported to have successful outcome. CONCLUSIONS: RPD-SMV/PV is feasible in carefully selected patients. The generalization of these results remains to be demonstrated.

2 Review Critical role of laser microdissection for genetic, epigenetic and proteomic analyses in pancreatic cancer. 2011

Funel, Niccola / Giovannetti, Elisa / Pollina, Luca E / del Chiaro, Marco / Mosca, Franco / Boggi, Ugo / Campani, Daniela. ·Department of Surgery, Unit of Experimental Surgical Pathology, University Hospital of Pisa, Via Paradisa 2, 56124 Pisa, Italy. niccolafunel@blu.it ·Expert Rev Mol Diagn · Pubmed #21902531.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease, and molecular studies to unravel novel biomarkers and therapeutic targets are warranted. However, PDAC is characterized by different precursor lesions, as well as by an intense desmoplastic reaction, with islet of neoplastic cells often representing a minor population. Moreover, normal ductal cells, which are considered to be the normal counterpart of pancreatic adenocarcinoma cells, comprise approximately 5% of the total population of cells making up this organ. For all these reasons, molecular techniques to identify critical mutations, as well as the pattern of altered mRNA/microRNA/protein expression should be performed on selected pancreatic cell subpopulations. Therefore, the use of the newest laser microdissection techniques is critical for the analysis of PDAC biological characteristics. This article highlights the most recent and clinically relevant aspects of genetic, epigenetic and proteomic analyses of PDAC from the perspective of the application of laser microdissection.

3 Clinical Trial Adjuvant chemoradiotherapy (gemcitabine-based) in pancreatic adenocarcinoma: the Pisa University experience. 2017

Sainato, Aldo / Montrone, Sabrina / Pasqualetti, Francesco / Coppola, Marianna / Cernusco, Nunzia L V / Panichi, Marco / Gonnelli, Alessandra / Vasile, Enrico / Morganti, Riccardo / Falcone, Alfredo / Boggi, Ugo / Paiar, Fabiola. ·Department of Radiotherapy, Pisa University, Pisa - Italy. · Department of Medical Oncology, Pisa University, Pisa - Italy. · Biostatistical Consulting Department of Oncology, Pisa University, Pisa - Italy. · Department of Surgery and Transplants, Pisa University, Pisa - Italy. ·Tumori · Pubmed #28708229.

ABSTRACT: INTRODUCTION: The role of adjuvant chemoradiotherapy in patients with pancreatic adenocarcinoma (PA) is controversial. In this study we aimed to assess the feasibility, disease-free survival (DFS) and overall survival (OS) of adjuvant chemoradiotherapy (gemcitabine based) in patients with resected PA and their correlation with prognostic factors. METHODS: 122 resected patients (stage ≥IIa) treated between February 1999 and December 2013 were analyzed. Two cycles of gemcitabine (1,000 mg/m2 on days 1, 8 and 15 every 28 days) were administered before concomitant radiotherapy (45 Gy/25 fractions) and chemotherapy (gemcitabine 300 mg/m2 weekly). RESULTS: Median follow-up was 22.7 months (range 4-109). Gastrointestinal toxicity (G3), neutropenia (G3-G4) and cardiac toxicity (G2-G3) were observed in 2.4%, 10.6% and 1.6% of patients, respectively. OS at 12, 24 and 60 months was 79%, 55% and 31%, respectively (median 25 months). Two-year OS in patients with postoperative Karnofsky performance status (KPS) ≤70 and ≥80 was 37.1% and 62.3%, respectively (p<0.0001). OS was better in the group of patients with a postoperative CA 19-9 level ≤100 U/mL (p = 0.014). Median DFS was 17 months. CONCLUSIONS: The combination of concomitant gemcitabine and radiotherapy in patients with radically resected PA was well tolerated and associated with a low incidence of local recurrences. Five-year OS was significantly influenced by postoperative KPS and CA 19-9 values.

4 Article Tumor Regression Grading Assessment in Locally Advanced Pancreatic Cancer After Neoadjuvant FOLFIRINOX: Interobserver Agreement and Prognostic Implications. 2020

Cacciato Insilla, Andrea / Vivaldi, Caterina / Giordano, Mirella / Vasile, Enrico / Cappelli, Carla / Kauffmann, Emanuele / Napoli, Niccolò / Falcone, Alfredo / Boggi, Ugo / Campani, Daniela. ·Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy. · Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, Pisa, Italy. · Division of Medical Oncology, Pisa University Hospital, Pisa, Italy. · Diagnostic and Interventional Radiology, Pisa University Hospital, Pisa, Italy. · Department of Transplant and General Surgery, University of Pisa, Pisa, Italy. ·Front Oncol · Pubmed #32117724.

ABSTRACT: Neoadjuvant therapy represents an increasingly used strategy in pancreatic cancer, and this means that more pancreatic resections need to be evaluated for therapy effect. Several grading systems have been proposed for the histological assessment of tumor regression in pre-treated patients with pancreatic cancer, but issues like practical application, level of agreement and prognostic significance are still debated. To date, a standardized and widely accepted score has not been established yet. In this study, two pathologists with expertise in pancreatic cancer used 4 of the most frequently reported systems (College of American Pathologists, Evans, MD Anderson, and Hartman) to evaluate tumor regression in 29 locally advanced pancreatic cancers previously treated with modified FOLFIRINOX regimen, to establish the level of agreement between pathologists and to determine their potential prognostic value. Cases were additionally evaluated with a fifth grading system inspired to the Dworak score, normally used for colo-rectal cancer, to identify an alternative, relevant option. Results obtained for current grading systems showed different levels of agreement, and they often proved to be very subjective and inaccurate. In addition, no significant correlation was observed with survival. Interestingly, Dworak score showed a higher degree of concordance and a significant correlation with overall survival in individual assessments. These data reflect the need to re-evaluate grading systems for pancreatic cancer to establish a more reproducible and clinically relevant score.

5 Article Early Tumor Shrinkage and Depth of Response Evaluation in Metastatic Pancreatic Cancer Treated with First Line Chemotherapy: An Observational Retrospective Cohort Study. 2019

Vivaldi, Caterina / Fornaro, Lorenzo / Cappelli, Carla / Pecora, Irene / Catanese, Silvia / Salani, Francesca / Cacciato Insilla, Andrea / Kauffmann, Emanuele / Donati, Francescamaria / Pasquini, Giulia / Massa, Valentina / Napoli, Niccolò / Lencioni, Monica / Boraschi, Piero / Campani, Daniela / Boggi, Ugo / Caramella, Davide / Falcone, Alfredo / Vasile, Enrico. ·Department of Translational Research and New Surgical and Medical Technologies, University of Pisa, Via Savi 6, 56126 Pisa, Italy. caterinavivaldi@gmail.com. · Division of Medical Oncology, Pisa University Hospital, Via Roma 67, 56126 Pisa, Italy. caterinavivaldi@gmail.com. · Division of Medical Oncology, Pisa University Hospital, Via Roma 67, 56126 Pisa, Italy. · Department of Diagnostic Imaging, Pisa University Hospital, Via Paradisa 2, 56124 Pisa, Italy. · Department of Surgical, Medical, Molecular Pathology and Critical Area, Division of Surgical Pathology, Pisa University Hospital, Via Paradisa 2, 56124 Pisa, Italy. · Department of Transplant and General Surgery, Pisa University Hospital, Via Paradisa 2, 56124 Pisa, Italy. · Diagnostic and Interventional Radiology, University of Pisa, Via Paradisa 2, 56124 Pisa, Italy. · Department of Translational Research and New Surgical and Medical Technologies, University of Pisa, Via Savi 6, 56126 Pisa, Italy. ·Cancers (Basel) · Pubmed #31277449.

ABSTRACT: Early tumor shrinkage (ETS) and depth of response (DoR) predict favorable outcomes in metastatic colorectal cancer. We aim to evaluate their prognostic role in metastatic pancreatic cancer (PC) patients treated with first-line modified-FOLFIRINOX (FOLFOXIRI) or Gemcitabine + Nab-paclitaxel (GemNab). Hence, 138 patients were tested for ETS, defined as a ≥20% reduction in the sum of target lesions' longest diameters (SLD) after 6-8 weeks from baseline, and DoR, i.e., the maximum percentage shrinkage in the SLD from baseline. Association of ETS and DoR with progression-free survival (PFS) and overall survival (OS) was assessed. ETS was reached in 49 patients (39.5% in the FOLFOXIRI, 29.8% in the GemNab group;

6 Article Short-term and long-term outcomes after robot-assisted versus laparoscopic distal pancreatectomy for pancreatic neuroendocrine tumors (pNETs): a multicenter comparative study. 2019

Alfieri, Sergio / Butturini, Giovanni / Boggi, Ugo / Pietrabissa, Andrea / Morelli, Luca / Vistoli, Fabio / Damoli, Isacco / Peri, Andrea / Fiorillo, Claudio / Pugliese, Luigi / Ramera, Marco / De Lio, Nelide / Di Franco, Gregorio / Esposito, Alessandro / Landoni, Luca / Rosa, Fausto / Menghi, Roberta / Doglietto, Giovanni Battista / Quero, Giuseppe / Anonymous2211048. ·Fondazione Policlinico "A.Gemelli" IRCCS of Rome, CRMPG (Gemelli Pancreatic Advanced Research Center), Università Cattolica del Sacro Cuore of Rome, Largo Agostino Gemelli 8, 00166, Rome, Italy. · Casa di Cura Pederzoli, Via Monte Baldo 24, 37019, Peschiera del Garda, Verona, Italy. · Chirurgia Generale Universitaria dell'Ospedale di Cisanello, Via Paradisa, 2, 56124, Pisa, Italy. · Fondazione IRCCS Policlinico San Matteo, Viale Camillo Golgi, 19, 27100, Pavia, Italy. · Dipartimento di Chirurgia Generale e Pancreatica, Policlinico G.B. Rossi, Piazzale Ludovico Antonio Scuro 10, 37134, Verona, Italy. · Fondazione Policlinico "A.Gemelli" IRCCS of Rome, CRMPG (Gemelli Pancreatic Advanced Research Center), Università Cattolica del Sacro Cuore of Rome, Largo Agostino Gemelli 8, 00166, Rome, Italy. giuseppe.quero@policlinicogemelli.it. · Digestive Surgical Unit, Department of Surgery, Fondation "A.Gemelli" Hospital of Rome, Catholic University of Sacred Hearth, Largo Agostino Gemelli, 8, 00168, Rome, Italy. giuseppe.quero@policlinicogemelli.it. ·Langenbecks Arch Surg · Pubmed #31055639.

ABSTRACT: PURPOSE: Minimally invasive surgery has increasingly gained popularity as a treatment of choice for pancreatectomy with encouraging initial results in robotic distal pancreatectomy (RDP). However, few data are available on the comparison between RDP and laparoscopic distal pancreatectomy (LDP) for pancreatic neuroendocrine tumors (pNETs). Our aim, thus, is to compare perioperative and long-term outcomes as well as total costs of RDP and LDP for pNETs. METHODS: All RDPs and LDPs for pNETs performed in four referral centers from 2008 to 2016 were included. Perioperative outcomes, histopathological results, overall (OS) and disease-free survival (DFS), and total costs were evaluated. RESULTS: Ninety-six RDPs and 85 LDPs were included. Demographic and clinical characteristics were comparable between the two cohorts. Operative time was 36.5 min longer in the RDP group (p = 0.009) but comparable to LDP after removing the docking time (247.9 vs 233.7 min; p = 0.6). LDP related to a lower spleen preservation rate (44.7% vs 65.3%; p < 0.0001) and higher blood loss (239.7 ± 112 vs 162.5 ± 98 cc; p < 0.0001). Advantages in operative time for RDP were documented in case of the spleen preservation procedures (265 ± 41.52 vs 291 ± 23 min; p = 0.04). Conversion rate, postoperative morbidity, and pancreatic fistula rate were similar between the two groups, as well as histopathological data, OS, and DFS. Significant advantages were evidenced for LDP regarding mean total costs (9235 (± 1935) € vs 11,226 (± 2365) €; p < 0.0001). CONCLUSIONS: Both RDP and LDP are safe and efficacious for pNETs treatment. However, RDP offers advantages with a higher spleen preservation rate and lower blood loss. Costs still remain the main limitation of the robotic approach.

7 Article 3 T MR perfusion of solid pancreatic lesions using dynamic contrast-enhanced DISCO sequence: Usefulness of qualitative and quantitative analyses in a pilot study. 2019

Donati, Francescamaria / Boraschi, Piero / Cervelli, Rosa / Pacciardi, Federica / Lombardo, Carlo / Boggi, Ugo / Falaschi, Fabio / Caramella, Davide. ·Department of Diagnostic Imaging, Pisa University Hospital, Via Paradisa 2, 56124 Pisa, Italy. · Department of Diagnostic Imaging, Pisa University Hospital, Via Paradisa 2, 56124 Pisa, Italy. Electronic address: p.boraschi@do.med.unipi.it. · Diagnostic and Interventional Radiology, University of Pisa, Via Paradisa 2, 56124 Pisa, Italy. · Division of General and Transplant Surgery, University of Pisa, Via Paradisa 2, 56124 Pisa, Italy. · Division of General and Transplant Surgery, University of Pisa, Via Paradisa 2, 56124 Pisa, Italy. Electronic address: u.boggi@med.unipi.it. · Department of Diagnostic Imaging, Pisa University Hospital, Via Paradisa 2, 56124 Pisa, Italy. Electronic address: f.falaschi@ao-pisa.toscana.it. · Diagnostic and Interventional Radiology, University of Pisa, Via Paradisa 2, 56124 Pisa, Italy. Electronic address: davide.caramella@med.unipi.it. ·Magn Reson Imaging · Pubmed #30878601.

ABSTRACT: PURPOSE: To assess the usefulness of qualitative and quantitative analyses of pancreatic focal diseases by using the dynamic contrast-enhanced Differential Subsampling with Cartesian Ordering (DISCO) sequence at 3 T MR device. MATERIALS AND METHODS: Ten patients without pancreatic diseases and twenty-five patients with pathologically confirmed pancreatic focal disease (ductal adenocarcinoma, n = 14; endocrine tumour, n = 8; focal chronic pancreatitis, n = 3), underwent MRI by 3 T-device. Multiphasic contrast-enhanced MR perfusion, consisting of a 3D axial navigator, based free-breathing T1-weighted DISCO sequence, was repeated for 5 min. A dose of 0.1 mL/kg of Gadobutrolo with a 20 mL saline flush was injected at a flow rate of 5 mL/s. Perfusion MRI were processed using a dedicated software package (GeniQ; GE Healthcare), obtaining both a time-signal-intensity curve (TSIC) and perfusion maps for each healthy pancreatic parenchyma and focal disease. The TSIC were grouped into four types according to their shapes and the MR perfusion parameters (Ktrans, Kep, Ve, IAUGC) were calculated. The one-way analysis of variance and the Student's t-test were used to correlate the quantitative and qualitative parameters with the tissue histology. RESULTS: All 10 patients with healthy pancreas presented a TSIC-type 1; TSIC-type 2 was observed in all 14 ductal adenocarcinomas and in one neuroendocrine tumour; TSIC-type 3 was recognized in the remaining 7 neuroendocrine neoplasms; TSIC-type 4 was identified in all 3 focal chronic pancreatitis. All perfusion parameters were significantly different (p < 0.0001) for each type of lesion. Furthermore, Ve was also very useful to discriminate between normal and pathological tissues (p = 0.0005). CONCLUSION: Qualitative and quantitative analyses of contrast-enhanced 3 T MR perfusion, using the dynamic contrast-enhanced DISCO sequence, could be considered an interesting tool to improve the diagnosis of focal pancreatic diseases, of solid lesions in particular. Further investigations with prospective larger sample studies are required to confirm these preliminary results.

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

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

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

9 Article Outcomes and Risk Score for Distal Pancreatectomy with Celiac Axis Resection (DP-CAR): An International Multicenter Analysis. 2019

Klompmaker, Sjors / Peters, Niek A / van Hilst, Jony / Bassi, Claudio / Boggi, Ugo / Busch, Olivier R / Niesen, Willem / Van Gulik, Thomas M / Javed, Ammar A / Kleeff, Jorg / Kawai, Manabu / Lesurtel, Mickael / Lombardo, Carlo / Moser, A James / Okada, Ken-Ichi / Popescu, Irinel / Prasad, Raj / Salvia, Roberto / Sauvanet, Alain / Sturesson, Christian / Weiss, Matthew J / Zeh, Herbert J / Zureikat, Amer H / Yamaue, Hiroki / Wolfgang, Christopher L / Hogg, Melissa E / Besselink, Marc G / Anonymous4750974. ·Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. · Department of Surgery, Johns Hopkins Hospital, Baltimore, MD, USA. · Department of Surgery, University of Utrecht Medical Center, Utrecht, The Netherlands. · Department of Surgery, Pancreas Institute University of Verona, Verona, Italy. · Division of General and Transplant Surgery, University of Pisa, Pisa, Italy. · Department of General, Visceral and Transplantation Surgery, Heidelberg University, Heidelberg, Germany. · Department of Visceral, Vascular and Endocrine Surgery, Martin-Luther-University Halle-Wittenberg, Halle, Saale, Germany. · Second Department of Surgery, Wakayama Medical University, Wakayama, Japan. · Department of Surgery and Liver Transplantation, Croix-Rousse University Hospital, Hospices Civils de Lyon, University of Lyon I, Lyon, France. · The Pancreas and Liver Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. · Center of General Surgery and Liver Transplant, Fundeni Clinical Institute, Bucharest, Romania. · Department of HPB and Transplant Services, National Health Service, Leeds, UK. · Department of HPB Surgery, Hôpital Beaujon, APHP, University Paris VII, Clichy, France. · Division of Surgery, Department for Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden. · Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA. · Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. · Department of Surgery, Northshore University HealthSystem, Chicago, IL, USA. · Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. m.g.besselink@amc.nl. ·Ann Surg Oncol · Pubmed #30610560.

ABSTRACT: BACKGROUND: Distal pancreatectomy with celiac axis resection (DP-CAR) is a treatment option for selected patients with pancreatic cancer involving the celiac axis. A recent multicenter European study reported a 90-day mortality rate of 16%, highlighting the importance of patient selection. The authors constructed a risk score to predict 90-day mortality and assessed oncologic outcomes. METHODS: This multicenter retrospective cohort study investigated patients undergoing DP-CAR at 20 European centers from 12 countries (model design 2000-2016) and three very-high-volume international centers in the United States and Japan (model validation 2004-2017). The area under receiver operator curve (AUC) and calibration plots were used for validation of the 90-day mortality risk model. Secondary outcomes included resection margin status, adjuvant therapy, and survival. RESULTS: For 191 DP-CAR patients, the 90-day mortality rate was 5.5% (95 confidence interval [CI], 2.2-11%) at 5 high-volume (≥ 1 DP-CAR/year) and 18% (95 CI, 9-30%) at 18 low-volume DP-CAR centers (P = 0.015). A risk score with age, sex, body mass index (BMI), American Society of Anesthesiologists (ASA) score, multivisceral resection, open versus minimally invasive surgery, and low- versus high-volume center performed well in both the design and validation cohorts (AUC, 0.79 vs 0.74; P = 0.642). For 174 patients with pancreatic ductal adenocarcinoma, the R0 resection rate was 60%, neoadjuvant and adjuvant therapies were applied for respectively 69% and 67% of the patients, and the median overall survival period was 19 months (95 CI, 15-25 months). CONCLUSIONS: When performed for selected patients at high-volume centers, DP-CAR is associated with acceptable 90-day mortality and overall survival. The authors propose a 90-day mortality risk score to improve patient selection and outcomes, with DP-CAR volume as the dominant predictor.

10 Article A propensity score-matched analysis of robotic versus open pancreatoduodenectomy for pancreatic cancer based on margin status. 2019

Kauffmann, Emanuele F / Napoli, Niccolò / Menonna, Francesca / Iacopi, Sara / Lombardo, Carlo / Bernardini, Juri / Amorese, Gabriella / Cacciato Insilla, Andrea / Funel, Niccola / Campani, Daniela / Cappelli, Carla / Caramella, Davide / Boggi, Ugo. ·Division of General and Transplant Surgery, University of Pisa, Pisa, Italy. · Division of Anesthesia and Intensive Care, University of Pisa, Pisa, Italy. · Division of Pathology, University of Pisa, Pisa, Italy. · Division of Radiology, University of Pisa, Pisa, Italy. · Division of General and Transplant Surgery, University of Pisa, Pisa, Italy. u.boggi@med.unipi.it. · Azienda Ospedaliera Universitaria Pisana, Università di Pisa, Via Paradisa 2, 56124, Pisa, Italy. u.boggi@med.unipi.it. ·Surg Endosc · Pubmed #29943061.

ABSTRACT: BACKGROUND: No study has shown the oncologic non-inferiority of robotic pancreatoduodenectomy (RPD) versus open pancreatoduodenectomy (OPD) for pancreatic cancer (PC). METHODS: This is a single institution propensity score matched study comparing RPD and ODP for resectable PC, based on factors predictive of R1 resection (≤ 1 mm). Only patients operated on after completion of the learning curve in both procedures and for whom circumferential margins were assessed according to the Leeds pathology protocol were included. The primary study endpoint was the rate of R1 resection. Secondary study endpoints were as follows: number of examined lymph nodes (N), rate of perioperative transfusions, percentage of patients receiving adjuvant therapies, occurrence of local recurrence, overall survival, disease-free survival, and sample size calculation for randomized controlled trials (RCT). RESULTS: Factors associated with R1 resection were tumor diameter, number of positive N, N ratio, logarithm odds of positive N, and duodenal infiltration. The matching process identified 20 RPDs and 24 OPDs. All RPDs were completed robotically. R1 resection was identified in 11 RPDs (55.0%) and in 10 OPDs (41.7%) (p = 0.38). There was no difference in the rate of R1 at each margin as well as in the proportion of patients with multiple R1 margins. RPD and OPD were also equivalent with respect to all secondary study endpoints, with a trend towards lower rate of blood transfusions in RPD. Based on the figures presented herein, a non-inferiority RCT comparing RPD and OPD having the rate of R1 resection as the primary study endpoint requires 3355 pairs. CONCLUSIONS: RPD and OPD achieved the same rate of R1 resections in resectable PC. RPD was also non-inferior to OPD with respect to all secondary study endpoints. Because of the high number of patients required to run a RCT, further assessment of RPD for PC would require the implementation of an international registry.

11 Article Minimally Invasive versus Open Distal Pancreatectomy for Ductal Adenocarcinoma (DIPLOMA): A Pan-European Propensity Score Matched Study. 2019

van Hilst, Jony / de Rooij, Thijs / Klompmaker, Sjors / Rawashdeh, Majd / Aleotti, Francesca / Al-Sarireh, Bilal / Alseidi, Adnan / Ateeb, Zeeshan / Balzano, Gianpaolo / Berrevoet, Frederik / Björnsson, Bergthor / Boggi, Ugo / Busch, Olivier R / Butturini, Giovanni / Casadei, Riccardo / Del Chiaro, Marco / Chikhladze, Sophia / Cipriani, Federica / van Dam, Ronald / Damoli, Isacco / van Dieren, Susan / Dokmak, Safi / Edwin, Bjørn / van Eijck, Casper / Fabre, Jean-Marie / Falconi, Massimo / Farges, Olivier / Fernández-Cruz, Laureano / Forgione, Antonello / Frigerio, Isabella / Fuks, David / Gavazzi, Francesca / Gayet, Brice / Giardino, Alessandro / Groot Koerkamp, Bas / Hackert, Thilo / Hassenpflug, Matthias / Kabir, Irfan / Keck, Tobias / Khatkov, Igor / Kusar, Masa / Lombardo, Carlo / Marchegiani, Giovanni / Marshall, Ryne / Menon, Krish V / Montorsi, Marco / Orville, Marion / de Pastena, Matteo / Pietrabissa, Andrea / Poves, Ignaci / Primrose, John / Pugliese, Raffaele / Ricci, Claudio / Roberts, Keith / Røsok, Bård / Sahakyan, Mushegh A / Sánchez-Cabús, Santiago / Sandström, Per / Scovel, Lauren / Solaini, Leonardo / Soonawalla, Zahir / Souche, F Régis / Sutcliffe, Robert P / Tiberio, Guido A / Tomazic, Aleš / Troisi, Roberto / Wellner, Ulrich / White, Steven / Wittel, Uwe A / Zerbi, Alessandro / Bassi, Claudio / Besselink, Marc G / Abu Hilal, Mohammed / Anonymous5620925. ·Department of Surgery, Cancer Center Amsterdam, Academic Medical Center, Amsterdam, the Netherlands. · Department of Surgery, Southampton University Hospital NHS Foundation Trust, Southampton, United Kingdom. · Department of Surgery, San Raffaele Hospital, Milan, Italy. · Department of Surgery, Morriston Hospital, Swansea, United Kingdom. · Department of Surgery, Virginia Mason Medical Center, Seattle, United States. · Department of Surgery, Karolinska Institute, Stockholm, Sweden. · Department of General and HPB surgery and liver transplantation, Ghent University Hospital, Ghent, Belgium. · Department of Surgery, Linköping University, Linköping, Sweden. · Department of Surgery, Universitá di Pisa, Pisa, Italy. · Department of Surgery, Pederzoli Hospital, Peschiera, Italy. · Department of Surgery, S. Orsola-Malpighi Hospital, Bologna, Italy. · Department of Surgery, Universitätsklinikum Freiburg, Freiburg, Germany. · Department of Surgery, Maastricht University Medical Center, Maastricht, the Netherlands. · Department of Surgery, Pancreas Institute, Verona University Hospital, Verona, Italy. · Department of Surgery, Hospital of Beaujon, Clichy, France. · Department of Surgery, Oslo University Hospital and Institute for Clinical Medicine, Oslo, Norway. · Department of Surgery, Erasmus MC, Rotterdam, the Netherlands. · Department of Surgery, Hopital Saint Eloi, Montpellier, France. · Department of Surgery, Hospital Clínic de Barcelona, Barcelona, Spain. · Department of Surgery, Niguarda Ca' Granda Hospital, Milan, Italy. · Department of Surgery, Institut Mutualiste Montsouris, Paris, France. · Department of Surgery, Humanitas University Hospital, Milan, Italy. · Department of Surgery, Heidelberg University Hospital, Heidelberg, Germany. · Department of Surgery, Oxford University Hospital NHS Foundation Trust, Oxford, United Kingdom. · Clinic for Surgery, UKSH Campus Lübeck, Lübeck, Germany. · Department of Surgery, Moscow Clinical Scientific Center, Moscow, Russian Federation. · Department of Surgery, University Medical Center Ljubljana, Ljubljana, Slovenia. · Department of Surgery, King's College Hospital NHS Foundation Trust, London, United Kingdom. · Department of Surgery, University hospital Pavia, Pavia, Italy. · Department of Surgery, Hospital del Mar, Barcelona, Spain. · Department of Surgery, University Hospital Birmingham, Birmingham, United Kingdom. · Surgical Clinic, Department of clinical and experimental sciences, University of Brescia, Brescia, Italy. · Department of Surgery, The Freeman Hospital Newcastle Upon Tyne, Newcastle, United Kingdom. ·Ann Surg · Pubmed #29099399.

ABSTRACT: OBJECTIVE: The aim of this study was to compare oncological outcomes after minimally invasive distal pancreatectomy (MIDP) with open distal pancreatectomy (ODP) in patients with pancreatic ductal adenocarcinoma (PDAC). BACKGROUND: Cohort studies have suggested superior short-term outcomes of MIDP vs. ODP. Recent international surveys, however, revealed that surgeons have concerns about the oncological outcomes of MIDP for PDAC. METHODS: This is a pan-European propensity score matched study including patients who underwent MIDP (laparoscopic or robot-assisted) or ODP for PDAC between January 1, 2007 and July 1, 2015. MIDP patients were matched to ODP patients in a 1:1 ratio. Main outcomes were radical (R0) resection, lymph node retrieval, and survival. RESULTS: In total, 1212 patients were included from 34 centers in 11 countries. Of 356 (29%) MIDP patients, 340 could be matched. After matching, the MIDP conversion rate was 19% (n = 62). Median blood loss [200 mL (60-400) vs 300 mL (150-500), P = 0.001] and hospital stay [8 (6-12) vs 9 (7-14) days, P < 0.001] were lower after MIDP. Clavien-Dindo grade ≥3 complications (18% vs 21%, P = 0.431) and 90-day mortality (2% vs 3%, P > 0.99) were comparable for MIDP and ODP, respectively. R0 resection rate was higher (67% vs 58%, P = 0.019), whereas Gerota's fascia resection (31% vs 60%, P < 0.001) and lymph node retrieval [14 (8-22) vs 22 (14-31), P < 0.001] were lower after MIDP. Median overall survival was 28 [95% confidence interval (CI), 22-34] versus 31 (95% CI, 26-36) months (P = 0.929). CONCLUSIONS: Comparable survival was seen after MIDP and ODP for PDAC, but the opposing differences in R0 resection rate, resection of Gerota's fascia, and lymph node retrieval strengthen the need for a randomized trial to confirm the oncological safety of MIDP.

12 Article Management of pregnancy-associated pancreatic cystic tumors: Review of the literature and results of a Pancreas Club Inc. Survey. 2018

Iacopi, Sara / Lombardo, Carlo / Menonna, Francesca / Mazzeo, Salvatore / Caramella, Davide / Amorese, Gabriella / Vistoli, Fabio / Boggi, Ugo. ·Division of General and Transplant Surgery, University of Pisa, Pisa, Italy. · Division of Radioloy, University of Pisa, Pisa, Italy. · Division of Anesthesia and Intensive Care, University of Pisa, Pisa, Italy. · Division of General and Transplant Surgery, University of Pisa, Pisa, Italy. Electronic address: u.boggi@med.unipi.it. ·Pancreatology · Pubmed #30274883.

ABSTRACT: BACKGROUND/OBJECTIVES: Management of patients with pregnancy-associated cyst pancreatic cystic tumors (PA-PCT) is complicated by lack of large series. METHODS: A systematic literature review was conducted to extrapolate data on management of PA-PCT, and make a questionnaire on pending issues to be administered to the members of the Pancreas Club Inc. RESULTS: The literature review demonstrated a total of 35 PA-PCT in 34 women, described exclusively in the form of case reports, and permitted the identification of eleven key questions to be addressed in the survey. The combined analysis of literature review and survery responses provided several information. First, PA-PCT are predominantly located in the body-tail of the pancreas, cause non-specific symptoms, are of large size (mean size: 11.2 ± 4.5 cm), and are nearly always malignant or premalignant, making timing of surgery, and not indication for surgery, the main issue in the management of these tumors. Second, there is a risk of PA-PCT rupture during pregnancy. Ruptured PA-PCT had a mean size 13.5 ± 4.9 cm, but no prognostic factor could be identified. Survey opinions suggested that this occurrence is quite rare, even for large tumors. Third, most pregnancies were conducted to term (mean gestational age: 40.5 ± 0.7 weeks), with a vaginal delivery. Fourth, all procedures were carried out through an open approach and the spleen was rarely preserved. Survey indicated instead that laparoscopy could play a role, and that the spleen should be preserved when feasible. CONCLUSIONS: PA-PCT require individualized treatment. The definition of a management algorithm requires the implementation of an International Registry.

13 Article Distal Pancreatectomy with Celiac Axis Resection (DP-CAR) for Pancreatic Cancer. How I do It. 2018

Klompmaker, Sjors / Boggi, Ugo / Hackert, Thilo / Salvia, Roberto / Weiss, Matthew / Yamaue, Hiroki / Zeh, Herbert J / Besselink, Marc G. ·Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands. · Division of General and Transplant Surgery, University of Pisa, Pisa, Italy. · Department of General, Visceral and Transplantation Surgery, Heidelberg University, Heidelberg, Germany. · Department of Surgery, University of Verona, Verona, Italy. · Department of Surgery, Johns Hopkins Hospital, Baltimore, MD, USA. · Second Department of Surgery, Wakayama Medical University, Wakayama, Japan. · Department of Surgery, UT Southwestern Medical Center, Dallas, TX, USA. · Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands. m.g.besselink@amc.nl. ·J Gastrointest Surg · Pubmed #30105677.

ABSTRACT: Approximately 30% of all pancreatic cancer patients have locally advanced (AJCC stage 3) disease. A sub-group of these patients-where the cancer only involves the celiac axis-may benefit from distal pancreatectomy with celiac axis resection (DP-CAR). Previous studies have shown that DP-CAR offers a survival benefit to a selected group of patients with otherwise unresectable pancreatic cancer, when performed by experienced pancreatic cancer treatment teams at high-volume centers. This article proposes a standardized approach to DP-CAR, including routine neoadjuvant (FOLFIRINOX) chemotherapy. This approach to selecting patients and performing DP-CAR has the potential to improve short-term outcomes and overall survival in selected patients, but it should be reserved for high-volume centers.

14 Article Evolution of pancreatectomy with en bloc venous resection for pancreatic cancer in Italy. Retrospective cohort study on 425 cases in 10 pancreatic referral units. 2018

Nigri, Giuseppe / Petrucciani, Niccolò / Pinna, Antonio Daniele / Ravaioli, Matteo / Jovine, Elio / Minni, Francesco / Grazi, Gian Luca / Chirletti, Piero / Balzano, Gianpaolo / Ferla, Fabio / De Carlis, Luciano / Tisone, Giuseppe / Napoli, Niccolò / Boggi, Ugo / Ramacciato, Giovanni. ·General Surgery and Hepato-pancreato-biliary Unit, Sapienza University of Rome, Sant'Andrea Hospital, Rome, Italy. Electronic address: giuseppe.nigri@uniroma1.it. · General Surgery and Hepato-pancreato-biliary Unit, Sapienza University of Rome, Sant'Andrea Hospital, Rome, Italy. · General Surgery and Transpantation Unit, University of Bologna, Policlinico Sant'Orsola Malpighi, Bologna, Italy. · General Surgery Unit, Ospedale Maggiore di Bologna, Italy. · General Surgery Unit, Policlinico Sant'Orsola Malpighi, Bologna, Italy. · Hepato-pancreato-biliary Surgery, IRCCS Regina Elena National Cancer Institute, Rome, Italy. · General Surgery Unit, Sapienza University of Rome, Policlinico Umberto I, Rome, Italy. · Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy. · Department of General Surgery and Transplantation, Niguarda Ca' Granda Hospital, Milan, Italy. · Transplantation Unit, University of Tor Vergata, Policlinico Tor Vergata, Roma, Italy. · General Surgery and Transplantation Unit, University of Pisa, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy. ·Int J Surg · Pubmed #29803770.

ABSTRACT: INTRODUCTION: The aim of this study is to analyze the evolution of pancreatectomy with venous resection in 10 referral Italian centers in the last 25 years. METHODS: A multicenter database of 425 patients submitted to pancreatectomy with venous resection between 1991 and 2015 was retrospectively analyzed. Patients were classified in 5 periods: 1 (1991-1995); 2 (1996-2000); 3 (2001-2005); 4 (2006-2010); 5 (2011-2015). Indications and outcomes were compared according to the period of surgery. RESULTS: Nineteen patients were operated in period 1, 28 in period 2, 91 in period 3, 140 in period 4, and 147 in period 5. Use of neoadjuvant therapy increased from 0% in period 1 and 2-12.1% in period 5. Postoperative complications ranged from 46.3% to 67.8%, and mortality from 5.3% to 9.2%. Median survival progressively increased, from 6 months in period 1-16 months in period 2, 24 months in period 3 and 4 and 35 months in period 5 (p = 0.004). Period, venous and nodal invasion were significant prognostic factors for survival. CONCLUSION: Management and outcomes of pancreatectomy with venous resection have evolved in the last 25 years in Italy. Improvement in patients' multidisciplinary management has lead to significant improvement of median survival.

15 Article Outcomes After Distal Pancreatectomy with Celiac Axis Resection for Pancreatic Cancer: A Pan-European Retrospective Cohort Study. 2018

Klompmaker, Sjors / van Hilst, Jony / Gerritsen, Sarah L / Adham, Mustapha / Teresa Albiol Quer, M / Bassi, Claudio / Berrevoet, Frederik / Boggi, Ugo / Busch, Olivier R / Cesaretti, Manuela / Dalla Valle, Raffaele / Darnis, Benjamin / De Pastena, Matteo / Del Chiaro, Marco / Grützmann, Robert / Diener, Markus K / Dumitrascu, Traian / Friess, Helmut / Ivanecz, Arpad / Karayiannakis, Anastasios / Fusai, Giuseppe K / Labori, Knut J / Lombardo, Carlo / López-Ben, Santiago / Mabrut, Jean-Yves / Niesen, Willem / Pardo, Fernando / Perinel, Julie / Popescu, Irinel / Roeyen, Geert / Sauvanet, Alain / Prasad, Raj / Sturesson, Christian / Lesurtel, Mickael / Kleeff, Jorg / Salvia, Roberto / Besselink, Marc G / Anonymous5490939. ·Department of Surgery, Cancer Center Amsterdam, Academic Medical Center, Amsterdam, the Netherlands. · Department of Digestive Surgery, E. Herriot Hospital, HCL, UCBL1, Lyon, France. · Department of Surgery, Hospital Universitari de Girona Dr. Josep Trueta, Girona, Spain. · Department of Surgery, University of Verona, Verona, Italy. · Department of General and HPB Surgery, Ghent University Hospital, Ghent, Belgium. · Division of General and Transplant Surgery, University of Pisa, Pisa, Italy. · Department of HPB Surgery, Hôpital Beaujon, Clichy Cedex, France. · Hepato-Pancreato-Biliary Unit, Parma University Hospital, Parma, Italy. · Department of Surgery and Liver Transplantation, Croix-Rousse University Hospital, Hospices Civils de Lyon, University of Lyon I, Lyon, France. · Department of Clinical Science, Intervention and Technology, Karolinska University Hospital, Stockholm, Sweden. · Department of Surgery, University Hospital Erlangen, Erlangen, Germany. · Department of General, Visceral and Transplantation Surgery, Heidelberg University, Heidelberg, Germany. · Center of General Surgery and Liver Transplant, Fundeni Clinical Institute, Bucharest, Romania. · Department of Surgery, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany. · Department of Abdominal and General Surgery, University Medical Centre Maribor, Maribor, Slovenia. · Second Department of Surgery, Democritus University of Thrace, Alexandroupolis, Greece. · HPB Surgery and Liver Transplantation Unit, Royal Free Hospital, London, UK. · Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Oslo, Norway. · Department of HPB and Transplant Surgery, Clínica Universidad de Navarra, Pamplona, Spain. · Department of Hepatobiliary, Endocrine and Transplantation Surgery, Antwerp University Hospital, Antwerp, Belgium. · Department of HPB and Transplant Services, National Health Service, Leeds, UK. · Department of Surgery, Skåne University Hospital, Lund, Sweden. · Department of Visceral, Vascular and Endocrine Surgery, Martin-Luther-University Halle-Wittenberg, Halle, Germany. · Department of Surgery, Cancer Center Amsterdam, Academic Medical Center, Amsterdam, the Netherlands. m.g.besselink@amc.nl. ·Ann Surg Oncol · Pubmed #29532342.

ABSTRACT: BACKGROUND: Western multicenter studies on distal pancreatectomy with celiac axis resection (DP-CAR), also known as the Appleby procedure, for locally advanced pancreatic cancer are lacking. We aimed to study overall survival, morbidity, mortality and the impact of preoperative hepatic artery embolization (PHAE). METHODS: Retrospective cohort study within the European-African Hepato-Pancreato-Biliary-Association, on DP-CAR between 1-1-2000 and 6-1-2016. Primary endpoint was overall survival. Secondary endpoints were radicality (R0-resection), 90-day mortality, major morbidity, and pancreatic fistulae (grade B/C). RESULTS: We included 68 patients from 20 hospitals in 12 countries. Postoperatively, 53% of patients had R0-resection, 25% major morbidity, 21% an ISGPS grade B/C pancreatic fistula, and 16% mortality. In total, 82% received (neo-)adjuvant chemotherapy and median overall survival in 62 patients with pancreatic ductal adenocarcinoma patients was 18 months (CI 10-37). We observed no impact of PHAE on ischemic complications. CONCLUSIONS: DP-CAR combined with chemotherapy for locally advanced pancreatic cancer is associated with acceptable overall survival. The 90-day mortality is too high and should be reduced. Future studies should investigate to what extent increasing surgical volume or better patient selection can improve outcomes.

16 Article Multicenter outcomes of robotic reconstruction during the early learning curve for minimally-invasive pancreaticoduodenectomy. 2018

Watkins, Ammara A / Kent, Tara S / Gooding, William E / Boggi, Ugo / Chalikonda, Sri / Kendrick, Michael L / Walsh, R Matthew / Zeh, Herbert J / Moser, A James. ·Pancreas and Liver Institute, Beth Israel Deaconess Medical Center, Boston, MA, USA. · The University of Pittsburgh Cancer Institute Biostatistics Facility, Pittsburgh, PA, USA. · University of Pisa, Pisa, Italy. · Departments of Surgery, Cleveland Clinic Foundation, Cleveland, OH, USA. · Mayo Clinic, Rochester, MN, USA. · University of Pittsburgh Medical Center, Pittsburgh, PA, USA. · Pancreas and Liver Institute, Beth Israel Deaconess Medical Center, Boston, MA, USA. Electronic address: ajmoser@bidmc.harvard.edu. ·HPB (Oxford) · Pubmed #28966031.

ABSTRACT: BACKGROUND: Perceived excess morbidity during the early learning curve of minimally-invasive pancreaticoduodenectomy (MIPD) has limited widespread adoption. It was hypothesized that robot-assisted reconstruction (RA) after MIPD allows anastomotic outcomes equivalent to open pancreaticoduodenectomy (PD). METHODS: Intent to treat analysis of centrally audited data accrued during early adoption of RA-MIPD at five centers. RESULTS: CUSUM analysis of operating times at each center identified 92 RA-MIPD during the early learning curve. Mean age was 65 ± 12 years with body mass index 25.8 ± 5.0. Surgical indications included malignant (60%) and premalignant (38%) lesions. Median operating time was 504 min (interquartile range 133) with 242 ml median estimated blood loss (IQR 398) and twelve (13%) conversions to open PD. Major complication rate (Clavien-Dindo III/IV) was 24% with 2 (2.2%) deaths and ten (10.9%) reoperations. Nine (9.9%) clinically significant pancreatic fistulae were observed (4 grade B; 5 grade C). Margin negative resection rate for malignancy was 90% (75% for PDA) with mean harvest of 16 ± 8 lymph nodes. CONCLUSIONS: These multicenter data during the early learning curve for RA-MIPD do not demonstrate excess anastomotic morbidity compared to open. Further studies are required to determine whether surgeon proficiency and evolving technique improve anastomotic outcomes compared to open.

17 Article Prognostic role of nodal ratio, LODDS, pN in patients with pancreatic cancer with venous involvement. 2017

Ramacciato, Giovanni / Nigri, Giuseppe / Petrucciani, Niccolo' / Pinna, Antonio Daniele / Ravaioli, Matteo / Jovine, Elio / Minni, Francesco / Grazi, Gian Luca / Chirletti, Piero / Tisone, Giuseppe / Ferla, Fabio / Napoli, Niccolo' / Boggi, Ugo. ·Department of Medical and Surgical Sciences and Translational Medicine, Faculty of Medicine and Psychology, St Andrea Hospital, Sapienza University, General Surgery Unit, Via di Grottarossa 1037, 00189, Rome, Italy. · Department of Medical and Surgical Sciences and Translational Medicine, Faculty of Medicine and Psychology, St Andrea Hospital, Sapienza University, General Surgery Unit, Via di Grottarossa 1037, 00189, Rome, Italy. giuseppe.nigri@uniroma1.it. · Department of Medical and Surgical Sciences-DIMEC, S. Orsola-Malpighi Hospital, Alma Mater Studiorum, University of Bologna, General Surgery and Transplantation Unit, Bologna, Italy. · General Surgery Unit, 'Maggiore' Hospital, Bologna, Italy. · Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, S. Orsola-Malpighi Hospital, University of Bologna, General Surgery Unit, Bologna, Italy. · Regina Elena National Cancer Institute IFO, Hepato-pancreato-biliary Surgery Unit, Rome, Italy. · Department of Surgical Sciences, Sapienza University of Rome, Policlinico Umberto I Hospital, General Surgery Unit, Rome, Italy. · Department of Experimental Medicine and Surgery, Liver Unit, Tor Vergata University of Rome, Rome, Italy. · Division of General Surgery and Transplantation Surgery, Niguarda Hospital, Milan, Italy. · Division of General Surgery and Transplantation Surgery, Pisa University Hospital, Pisa, Italy. ·BMC Surg · Pubmed #29169392.

ABSTRACT: BACKGROUND: The UICC/AJCC TNM staging system classifies lymph nodes as N0 and N1 in pancreatic cancer. Aim of the study is to determine whether the number of examine nodes, the nodal ratio (NR) and the logarithm odds of positive lymph nodes (LODDS) may better stratify the prognosis of patients undergoing pancreatectomy combined with venous resection for pancreatic cancer with venous involvement. METHODS: A multicenter database of 303 patients undergoing pancreatectomy in 9 Italian referral centers was analyzed. The prognostic impact of number of retrieved and examined nodes, NR, LODDS was analyzed and compared with ROC curves analysis, Pearson test, univariate and multivariate analysis. RESULTS: The number of metastatic nodes, pN, the NR and LODDS was significantly correlated with survival at multivariate analyses. The corresponding AUC for the number of metastatic nodes, pN, the NR and LODDS were 0.66, 0.69, 0.63 and 0.65, respectively. The Pearson test showed a significant correlation between the number of retrieved lymph nodes and number of metastatic nodes, pN and the NR. LODDS had the lower coefficient correlation. Concerning N1 patients, the NR, the LODDS and the number of metastatic nodes were able to significantly further stratify survival (p = 0.040; p = 0.046; p = 0.038, respectively). CONCLUSIONS: The number of examined lymph nodes, the NR and LODDS are useful for further prognostic stratification of N1 patients in the setting of pancreatectomy combined with PV/SMV resection. No superiority of one over the others methods was detected.

18 Article Phospho-Akt overexpression is prognostic and can be used to tailor the synergistic interaction of Akt inhibitors with gemcitabine in pancreatic cancer. 2017

Massihnia, Daniela / Avan, Amir / Funel, Niccola / Maftouh, Mina / van Krieken, Anne / Granchi, Carlotta / Raktoe, Rajiv / Boggi, Ugo / Aicher, Babette / Minutolo, Filippo / Russo, Antonio / Leon, Leticia G / Peters, Godefridus J / Giovannetti, Elisa. ·Department of Medical Oncology VU University Medical Center, Cancer Center Amsterdam, CCA room 1.52, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. · Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy. · Metabolic syndrome Research center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. · Cancer Pharmacology Lab, AIRC Start Up Unit, University of Pisa, Pisa, Italy. · Department of Pharmacy, University of Pisa, Pisa, Italy. · Department of Surgery, University of Pisa, Pisa, Italy. · Æterna Zentaris GmbH, Frankfurt am Main, Frankfurt, Germany. · Department of Medical Oncology VU University Medical Center, Cancer Center Amsterdam, CCA room 1.52, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. e.giovannetti@vumc.nl. · Cancer Pharmacology Lab, AIRC Start Up Unit, University of Pisa, Pisa, Italy. e.giovannetti@vumc.nl. ·J Hematol Oncol · Pubmed #28061880.

ABSTRACT: BACKGROUND: There is increasing evidence of a constitutive activation of Akt in pancreatic ductal adenocarcinoma (PDAC), associated with poor prognosis and chemoresistance. Therefore, we evaluated the expression of phospho-Akt in PDAC tissues and cells, and investigated molecular mechanisms influencing the therapeutic potential of Akt inhibition in combination with gemcitabine. METHODS: Phospho-Akt expression was evaluated by immunohistochemistry in tissue microarrays (TMAs) with specimens tissue from radically-resected patients (n = 100). Data were analyzed by Fisher and log-rank test. In vitro studies were performed in 14 PDAC cells, including seven primary cultures, characterized for their Akt1 mRNA and phospho-Akt/Akt levels by quantitative-RT-PCR and immunocytochemistry. Growth inhibitory effects of Akt inhibitors and gemcitabine were evaluated by SRB assay, whereas modulation of Akt and phospho-Akt was investigated by Western blotting and ELISA. Cell cycle perturbation, apoptosis-induction, and anti-migratory behaviors were studied by flow cytometry, AnnexinV, membrane potential, and migration assay, while pharmacological interaction with gemcitabine was determined with combination index (CI) method. RESULTS: Immunohistochemistry of TMAs revealed a correlation between phospho-Akt expression and worse outcome, particularly in patients with the highest phospho-Akt levels, who had significantly shorter overall and progression-free-survival. Similar expression levels were detected in LPC028 primary cells, while LPC006 were characterized by low phospho-Akt. Remarkably, Akt inhibitors reduced cancer cell growth in monolayers and spheroids and synergistically enhanced the antiproliferative activity of gemcitabine in LPC028, while this combination was antagonistic in LPC006 cells. The synergistic effect was paralleled by a reduced expression of ribonucleotide reductase, potentially facilitating gemcitabine cytotoxicity. Inhibition of Akt decreased cell migration and invasion, which was additionally reduced by the combination with gemcitabine. This combination significantly increased apoptosis, associated with induction of caspase-3/6/8/9, PARP and BAD, and inhibition of Bcl-2 and NF-kB in LPC028, but not in LPC006 cells. However, targeting the key glucose transporter Glut1 resulted in similar apoptosis induction in LPC006 cells. CONCLUSIONS: These data support the analysis of phospho-Akt expression as both a prognostic and a predictive biomarker, for the rational development of new combination therapies targeting the Akt pathway in PDAC. Finally, inhibition of Glut1 might overcome resistance to these therapies and warrants further studies.

19 Article Indications, technique, and results of robotic pancreatoduodenectomy. 2016

Napoli, Niccolò / Kauffmann, Emanuele F / Menonna, Francesca / Perrone, Vittorio Grazio / Brozzetti, Stefania / Boggi, Ugo. ·Division of General and Transplant Surgery, University of Pisa, Pisa, Italy. · Pietro Valdoni Department of Surgery, University of Rome La Sapienza, Rome, Italy. · Division of General and Transplant Surgery, University of Pisa, Pisa, Italy. u.boggi@med.unipi.it. ·Updates Surg · Pubmed #27614901.

ABSTRACT: Robotic assistance improves surgical dexterity in minimally invasive operations, especially when fine dissection and multiple sutures are required. As such, robotic assistance could be rewarding in the setting of robotic pancreatoduodenectomy (RPD). RPD was implemented at a high volume center with preemptive experience in advanced laparoscopy. Indications, surgical technique, and results of RPD are discussed against the background of current literature. RPD was performed in 112 consecutive patients. Conversion to open surgery was required in three patients, despite nine required segmental resection and reconstruction of the superior mesenteric/portal vein. No patient was converted to laparoscopy. A pancreato-jejunostomy was created in 106 patients (94.6 %), using either a duct-to-mucosa (n = 82; 73.2 %) or an invaginating (n = 24; 21.4 %) technique. Pancreato-gastrostomy was performed in one patient, the pancreatic duct was occluded in two patients, and a pancreatico-cutaneous fistula was created in three patients. Mean operative time was 526.3 ± 102.4 in the entire cohort and reduced significantly over the course of time. Experience was also associated with reduced rates of delayed gastric emptying and increased proportion of malignant tumor histology. Ninety day mortality was 3.6 %. Postoperative complications occurred in 83 patients (74.1 %) with a median comprehensive complication index of 20.9 (0-30.8). Clinically relevant pancreatic fistula occurred in 19.6 % of the patients. No grade C pancreatic fistula was noted in the last 72 consecutive patients. RPD is safely feasible in selected patients. Implementation of RPD requires sound experience with open pancreatoduodenectomy and advanced laparoscopic procedures, as well as specific training with the robotic platform.

20 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.

21 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.

22 Article Robotic-Assisted Pancreatic Resections. 2016

Boggi, Ugo / Napoli, Niccolò / Costa, Francesca / Kauffmann, Emanuele F / Menonna, Francesca / Iacopi, Sara / Vistoli, Fabio / Amorese, Gabriella. ·Division of General and Transplant Surgery, University of Pisa, Pisa, Italy. u.boggi@med.unipi.it. · Division of General and Transplant Surgery, University of Pisa, Pisa, Italy. · Division of Anesthesia and Intensive Care, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy. ·World J Surg · Pubmed #27206401.

ABSTRACT: BACKGROUND: Robotic assistance enhances surgical dexterity and could facilitate wider adoption of laparoscopy for pancreatic resections (PR). METHODS: Data were prospectively entered into a database and analyzed retrospectively to assess feasibility and safety of robotic-assisted PR (RAPR). Additionally, robotic-assisted pancreaticoduodenectomy (RAPD) was compared to a contemporary group of open pancreaticoduodenectomies (OPD). RESULTS: Between October 2008 and October 2014, 200 consecutive patients underwent RAPR. Three procedures were converted to open surgery (1.5 %), despite 14 patients required associated vascular procedures. RAPD was performed in 83 patients (41.5 %), distal pancreatectomy in 83 (41.5 %), total pancreatectomy in 17 (8.5 %), tumor enucleation in 12 (6 %), and central pancreatectomy in 5 (2.5 %). Thirty-day and 90-day mortality rates were 0.5 and 1 %, respectively. Both deaths occurred after RAPD with vein resection. Complications occurred in 63.0 % of the patients (≥Clavien-Dindo grade IIIb in 4 %). Median comprehensive complication index was 20.9 (0-26.2). Incidence of grade B/C pancreatic fistula was 28.0 %. Reoperation was required in 14 patients (7.0 %). The risk of reoperation decreased after post-operative day 20 (OR 0.072) (p = 0.0015). When compared to OPD, RAPD was associated with longer mean operative time (527.2 ± 166.1 vs. 425.3 ± 92.7; <0.0001) but had an equivalent safety profile. The median number of examined lymph nodes (37; 28.8-45.3 vs. 36; 28-52.8) and the rate of margin positivity in patients diagnosed with pancreatic cancer were also similar (12.5 vs. 45.5 %). CONCLUSIONS: RAPR, including RAPD, are safely feasible in selected patients. The results of RAPD in pancreatic cancer are encouraging but deserve further investigation.

23 Article Pancreatectomy with Mesenteric and Portal Vein Resection for Borderline Resectable Pancreatic Cancer: Multicenter Study of 406 Patients. 2016

Ramacciato, Giovanni / Nigri, Giuseppe / Petrucciani, Niccolò / Pinna, Antonio Daniele / Ravaioli, Matteo / Jovine, Elio / Minni, Francesco / Grazi, Gian Luca / Chirletti, Piero / Tisone, Giuseppe / Napoli, Niccolò / Boggi, Ugo. ·Department of Medical and Surgical Sciences and Translational Medicine, Faculty of Medicine and Psychology, St Andrea Hospital, Sapienza University, General Surgery Unit, Rome, Italy. · Department of Medical and Surgical Sciences and Translational Medicine, Faculty of Medicine and Psychology, St Andrea Hospital, Sapienza University, General Surgery Unit, Rome, Italy. giuseppe.nigri@uniroma1.it. · Department of Medical and Surgical Sciences-DIMEC, S. Orsola-Malpighi Hospital, Alma Mater Studiorum, University of Bologna, General Surgery and Transplantation Unit, Bologna, Italy. · General Surgery Unit, 'Maggiore' Hospital, Bologna, Italy. · Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, S. Orsola-Malpighi Hospital, University of Bologna, General Surgery Unit, Bologna, Italy. · Regina Elena National Cancer Institute IFO, Hepato-pancreato-biliary Surgery Unit, Rome, Italy. · Department of Surgical Sciences, Sapienza University of Rome, Policlinico Umberto I Hospital, General Surgery Unit, Rome, Italy. · Department of Experimental Medicine and Surgery, Liver Unit, Tor Vergata University of Rome, Rome, Italy. · Division of General and Transplant Surgery, Pisa University Hospital, Pisa, Italy. ·Ann Surg Oncol · Pubmed #26893222.

ABSTRACT: PURPOSE: The role of pancreatectomy with en bloc venous resection and the prognostic impact of pathological venous invasion are still debated. The authors analyzed perioperative, survival results, and prognostic factors of pancreatectomy with en bloc portal (PV) or superior mesenteric vein (SMV) resection for borderline resectable pancreatic carcinoma, focusing on predictive factors of histological venous invasion and its prognostic role. METHODS: A multicenter database of 406 patients submitted to pancreatectomy with en bloc SMV and/or PV resection for pancreatic adenocarcinoma was analyzed retrospectively. Univariate and multivariate analysis of factors related to histological venous invasion were performed using logistic regression model. Prognostic factors were analyzed with log-rank test and multivariate proportional hazard regression analysis. RESULTS: Complications occurred in 51.9 % of patients and postoperative death in 7.1 %. Histological invasion of the resected vein was confirmed in 56.7 % of specimens. Five-year survival was 24.4 % with median survival of 24 months. Vein invasion at preoperative computed tomography (CT), N status, number of metastatic lymph nodes, preoperative serum albumin were related to pathological venous invasion at univariate analysis, and vein invasion at CT was independently related to venous invasion at multivariate analysis. Use of preoperative biliary drain was significantly associated with postoperative complications. Multivariate proportional hazard regression analysis demonstrated a significant correlation between overall survival and histological venous invasion and administration of adjuvant therapy. CONCLUSIONS: This study identifies predictive factors of pathological venous invasion and prognostic factors for overall survival, including pathological venous invasion, which may help with patients' selection for different treatment protocols.

24 Article Prognostic factors for pancreatic neuroendocrine neoplasms (pNET) and the risk of small non-functioning pNET. 2015

Lombardi, M / De Lio, N / Funel, N / Sardella, C / Russo, D / Urbani, C / Rossi, G / Campani, D / Martino, E / Marcocci, C / Boggi, U / Bogazzi, F. ·Department of Clinical and Experimental Medicine, University of Pisa, Ospedale Cisanello, Via Paradisa 2, 56124, Pisa, Italy. marty81@tiscali.it. · Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy. · Department of Surgical, Medical and Molecular Pathology of Critical Area, University of Pisa, Pisa, Italy. · Department of Clinical and Experimental Medicine, University of Pisa, Ospedale Cisanello, Via Paradisa 2, 56124, Pisa, Italy. · Unit of Epidemiology and Biostatistics, Institute of Clinical Physiology, National Research Council, Pisa, Italy. ·J Endocrinol Invest · Pubmed #25501604.

ABSTRACT: BACKGROUND: Non-functioning (NF) pancreatic neuroendocrine tumors (pNET) often have an indolent outcome. A consensus to submit patients with large (>2 cm) NF-pNET to surgery already exists; but a conservative approach for small (≤2 cm) NF neoplasms has been proposed. AIM: To identify prognostic factors for survival and progression free survival (PFS) of NF-pNET, evaluating whether surgery may be avoided for small NF-pNET. SUBJECTS AND METHODS: Retrospective study of 77 consecutive patients with pNET submitted to surgery, of which 60 were NF. Pathological tissues were revised according to the 2000 and 2010 WHO classifications. Risk factors for survival and PFS were evaluated using the Kaplan-Meier method and the Cox regression model. RESULTS: The 8-year cause-specific survival of NF-pNET was 79.3%. At univariate analysis, high grading, high staging, large tumors, angioinvasion and peri-pancreatic infiltration were significantly associated with a shorter survival; at multivariate analysis only peri-pancreatic infiltration was significantly associated with a shorter NF-pNET survival. Most small NF-pNET were grade 1 (74%), compared to large NF-pNET (27%). Distant metastases were present in 29.7% (n = 11) and 17.4% (n = 4) of patients with large or small NF-pNET, respectively; among the 19 small NF-pNET without metastasis, five had a local malignancy (lymph node metastasis or local infiltration); thus, 39% of the 23 NF-pNET, turned out to have a malignant potential. CONCLUSIONS: Among NF-pNET, large neoplasms were associated with worse outcomes; however, small NF-pNET do not seem to have an invariable benign behavior. Whether surgery should be avoided in all patients with small NF-pNET is questionable.

25 Article Contrast enhancement pattern on multidetector CT predicts malignancy in pancreatic endocrine tumours. 2015

Cappelli, Carla / Boggi, Ugo / Mazzeo, Salvatore / Cervelli, Rosa / Campani, Daniela / Funel, Niccola / Contillo, Benedetta Pontillo / Bartolozzi, Carlo. ·Diagnostic and Interventional Radiology, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy, carlacappelli1@gmail.com. ·Eur Radiol · Pubmed #25447971.

ABSTRACT: OBJECTIVES: Preoperative suspicion of malignancy in pancreatic neuroendocrine tumours (pNETs) is mostly based on tumour size. We retrospectively reviewed the contrast enhancement pattern (CEP) of a series of pNETs on multiphasic multidetector computed tomography (MDCT), to identify further imaging features predictive of lesion aggressiveness. METHODS: Sixty pNETs, diagnosed in 52 patients, were classified based on CEP as: type A showing early contrast enhancement and rapid wash-out; type B presenting even (B1) or only (B2) late enhancement. All tumours were resected allowing pathologic correlations. RESULTS: Nineteen pNETs showed type A CEP (5-20 mm), 29 type B1 CEP (5-80 mm) and 12 type B2 (15-100 mm). All tumours were classified as well differentiated tumours, 19 were benign (WDt-b), 15 with uncertain behaviour (WDt-u) and 26 carcinomas (WDC). None of A lesions were malignant (12 WDt-b; 7 WDt-u), all B2 lesions were WDC, 7 B1 lesions were WDt-b, 8 WDt-u and 14 WDC; 4/34 (12 %) lesions ≤2cm were WDC. CEP showed correlation with all histological prognostic indicators. CONCLUSIONS: Correlating with the lesion grading and other histological prognostic predictors, CEP may preoperatively suggest the behaviour of pNETs, assisting decisions about treatment. Moreover CEP allows recognition of malignant small tumours, incorrectly classified on the basis of their dimension.

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