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Pancreatic Neoplasms: HELP
Articles by Stefano Partelli
Based on 85 articles published since 2010
(Why 85 articles?)
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Between 2010 and 2020, S. Partelli wrote the following 85 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4
26 Article Risk and Predictors of Postoperative Morbidity and Mortality After Pancreaticoduodenectomy for Pancreatic Neuroendocrine Neoplasms: A Comparative Study With Pancreatic Ductal Adenocarcinoma. 2019

Partelli, Stefano / Tamburrino, Domenico / Cherif, Rim / Muffatti, Francesca / Moggia, Elisabetta / Gaujoux, Sébastien / Sauvanet, Alain / Falconi, Massimo / Fusai, Giuseppe. ·Department of HPB and Liver Transplant Surgery, Royal Free Hospital, NHS Foundation Trust, London, United Kingdom. · Chirurgie Hépato-Bilio-Pancréatique, Beaujon Hospital, Paris. ·Pancreas · Pubmed #30946244.

ABSTRACT: OBJECTIVES: Pancreaticoduodenectomy (PD) is associated with a high risk of postoperative complications and mortality. The aim of this study was to compare postoperative morbidity after PD in patients undergoing resections for pancreatic neuroendocrine neoplasms (PanNENs) with patients undergoing the same resection for pancreatic ductal adenocarcinoma (PDAC). METHODS: Data of 566 patients from 3 European tertiary referral centers between 1998 and 2014 were considered. RESULTS: Overall, 566 patients (179 with PanNENs, 387 with PDAC) who underwent PD were analyzed. Patients with PanNENs were significantly younger (56 vs 64 years, P < 0.0001). The consistency of the pancreas was soft in 147 patients (82%) with PanNENs and in 162 patients (42%) with PDAC (P < 0.0001). Patients in the PanNENs group had a significantly higher rate of pancreatic fistula (P < 0.0001), bile leak (P = 0.004), abdominal collection (P = 0.017), and development of sepsis (P = 0.042). No differences in terms of overall postoperative complications, median length of stay, and in-hospital mortality were found. On multivariate analysis sex (male), PanNENs indication, blood transfusion, and a soft pancreatic texture were independent predictors of pancreatic fistula after PD. CONCLUSIONS: Pancreaticoduodenectomy for PanNENs is associated with higher rate of surgical-specific postoperative complications than those for PDAC.

27 Article Ct radiomic features of pancreatic neuroendocrine neoplasms (panNEN) are robust against delineation uncertainty. 2019

Mori, Martina / Benedetti, Giulia / Partelli, Stefano / Sini, Carla / Andreasi, Valentina / Broggi, Sara / Barbera, Maurizio / Cattaneo, Giovanni M / Muffatti, Francesca / Panzeri, Marta / Falconi, Massimo / Fiorino, Claudio / De Cobelli, Francesco. ·Medical Physics, San Raffaele Scientific Institute, Milano, Italy. · Radiology, San Raffaele Scientific Institute, Milano, Italy. · Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, Milano, Italy; Vita-Salute University, Milano, Italy. · Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, Milano, Italy. · Radiology, San Raffaele Scientific Institute, Milano, Italy; Vita-Salute University, Milano, Italy. · Medical Physics, San Raffaele Scientific Institute, Milano, Italy. Electronic address: fiorino.claudio@hsr.it. ·Phys Med · Pubmed #30738530.

ABSTRACT: PURPOSE: The aim of this study was to quantify the impact of CT delineation uncertainty of pancreatic neuroendocrine neoplasms (panNEN) on Radiomic features (RF). METHODS: Thirty-one previously operated patients were considered. Three expert radiologists contoured panNEN lesions on pre-surgical high-resolution contrast-enhanced CT images and contours were transferred onto pre-contrast CT. Volume agreement was quantified by the DICE index. After images resampling and re-binning, 69 RF were extracted and the impact of inter-observer variability was assessed by Intra-Class Correlation (ICC): ICC > 0.80 was considered as a threshold for "very high" inter-observer agreement. RESULTS: The median volume was 1.3 cc (range: 0.2-110 cc); a satisfactory inter-observer volume agreement was found (mean DICE = 0.78). Only 4 RF showed ICC < 0.80 (0.48-0.73), including asphericity and three RFs (of five) of the neighborhood intensity difference matrix (NID). CONCLUSIONS: The impact of inter-observer variability in delineating panNEN on RF was minimum, with the exception of the NID family and asphericity, showing a moderate agreement. These results support the feasibility of studies aiming to assess CT radiomic biomarkers for panNEN.

28 Article Association between preoperative Vasostatin-1 and pathological features of aggressiveness in localized nonfunctioning pancreatic neuroendocrine tumors (NF-PanNET). 2019

Andreasi, Valentina / Partelli, Stefano / Manzoni, Marco / Muffatti, Francesca / Colombo, Barbara / Corti, Angelo / Falconi, Massimo. ·Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy; "Vita e Salute" University, Milan, Italy. · Endocrinology Unit, San Raffaele Scientific Institute, Milan, Italy. · Experimental Oncology Division, San Raffaele Scientific Institute, Milan, Italy. · Experimental Oncology Division, San Raffaele Scientific Institute, Milan, Italy; "Vita e Salute" University, Milan, Italy. · Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy; "Vita e Salute" University, Milan, Italy. Electronic address: falconi.massimo@hsr.it. ·Pancreatology · Pubmed #30470614.

ABSTRACT: BACKGROUND: A reliable and accessible biomarker for nonfunctioning pancreatic neuroendocrine tumors (NF-PanNET) is currently unavailable. Chromogranin A (CgA) represents the best-described neuroendocrine biomarker, but its accuracy is low. Vasostatin-1 (VS-1), a fragment derived from the cleavage of CgA, was recently investigated and found to be more accurate as tumor biomarker in a cohort of patients affected by mainly metastatic small intestinal NET. METHODS: Patients submitted to surgery for sporadic localized NF-PanNET at San Raffaele Hospital were included. Preoperative plasma samples were prospectively collected. Circulating levels of total-CgA and VS-1 were retrospectively investigated by sandwich Enzyme-Linked ImmunoSorbent Assays. RESULTS: Overall, 50 patients were included. VS-1 value (P=0.0001) was the only preoperatively retrievable factor independently associated with NF-PanNET size. No significant correlation between CgA and tumor diameter was found (P = 0.057). A VS-1 value of 0.39 nM was identified as the optimal VS-1 cut-off accurately associated with NF-PanNET larger than 4 cm. Patients with VS-1 > 0.39 nM had a significantly higher frequency of microvascular invasion (P = 0.005) and nodal metastasis (P = 0.027). Median VS-1 plasma level was significantly higher in the presence of microvascular invasion (P = 0.001) and nodal metastasis (P = 0.012). PPI assumption significantly increased total-CgA levels, but not those of VS-1 (P = 0.111). CONCLUSIONS: In localized, non-metastatic NF-PanNET, VS-1 is strongly associated to tumor dimension and its plasma levels are significantly higher in the presence of microvascular invasion and nodal metastases; moreover, VS-1 value is not affected by the PPI use.

29 Article Competitive Testing of the WHO 2010 versus the WHO 2017 Grading of Pancreatic Neuroendocrine Neoplasms: Data from a Large International Cohort Study. 2018

Rindi, Guido / Klersy, Catherine / Albarello, Luca / Baudin, Eric / Bianchi, Antonio / Buchler, Markus W / Caplin, Martyn / Couvelard, Anne / Cros, Jérôme / de Herder, Wouter W / Delle Fave, Gianfranco / Doglioni, Claudio / Federspiel, Birgitte / Fischer, Lars / Fusai, Giuseppe / Gavazzi, Francesca / Hansen, Carsten P / Inzani, Frediano / Jann, Henning / Komminoth, Paul / Knigge, Ulrich P / Landoni, Luca / La Rosa, Stefano / Lawlor, Rita T / Luong, Tu V / Marinoni, Ilaria / Panzuto, F / Pape, Ulrich-Frank / Partelli, Stefano / Perren, Aurel / Rinzivillo, Maria / Rubini, Corrado / Ruszniewski, Philippe / Scarpa, Aldo / Schmitt, Anja / Schinzari, Giovanni / Scoazec, Jean-Yves / Sessa, Fausto / Solcia, Enrico / Spaggiari, Paola / Toumpanakis, Christos / Vanoli, Alessandro / Wiedenmann, Bertram / Zamboni, Giuseppe / Zandee, Wouter T / Zerbi, Alessandro / Falconi, Massimo. ·Institute of Pathology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma-Università Cattolica del Sacro Cuore, Roma ENETS Center of Excellence, Rome, Italyguido.rindi@unicatt.it. · Service of Biometry and Clinical Epidemiology, Research Department, and IRCCS Fondazione Policlinico San Matteo, Pavia, Italy. · Pathology Unit, San Raffaele Scientific Institute, Milan, Italy. · Department of Oncology, Cancer Campus, Villejuif, France. · Department of Endocrinology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma-Università Cattolica del Sacro Cuore, Roma ENETS Center of Excellence, Rome, Italy. · Department of Surgery, University Hospital Heidelberg, Neu Heidelberg, Germany. · Neuroendocrine Tumour Unit, Centre for Gastroenterology, London, United Kingdom. · Department of Pathology, Hopital Beaujon, Paris ENETS Center of Excellence, Clichy, France. · Section Endocrinology, Department of Internal Medicine, Erasmus University Medical Center and and Erasmus MC Cancer Institute Rotterdam, Rotterdam ENETS Center of Excellence, Rotterdam, The Netherlands. · Digestive and Liver Disease Unit, Sant'Andrea University Hospital, Roma ENETS Center of Excellence, Rome, Italy. · Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Copenhagen ENETS Center of Excellence, Copenhagen, Denmark. · Department of Surgery, University College, Royal Free Hospital, London ENETS Center of Excellence, London, United Kingdom. · Pancreatic Surgery, Humanitas Clinical and Research Center, Humanitas Milan ENETS Center of Excellence, Milan, Italy. · Department of Surgery, Rigshospitalet, Copenhagen University Hospital, Copenhagen ENETS Center of Excellence, Copenhagen, Denmark. · Institute of Pathology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma-Università Cattolica del Sacro Cuore, Roma ENETS Center of Excellence, Rome, Italy. · Department of Hepatology and Gastroenterology, Charité, Campus Virchow Klinikum and Charite Mitte, University Medicine Berlin, Berlin ENETS Center of Excellence, Berlin, Germany. · Institute of Pathology, Stadtspital Triemli, Zurich, Switzerland. · Department of Surgery and Oncology, General and Pancreatic Surgery, The Pancreas Institute, Verona ENETS Center of Excellence, Verona, Italy. · Department of Pathology, Ospedale di Circolo, Università dell'Insubria, Varese, Italy. · Section of Pathology and ARC-Net Research Centre, Department of Diagnostics and Public Health, University and Hospital Trust of Verona, Verona ENETS Center of Excellence, Verona, Italy. · Department of Pathology, University College, Royal Free Hospital, London ENETS Center of Excellence, London, United Kingdom. · Institute of Pathology, University of Bern, Bern, Switzerland. · Pancreatic Surgery Unit, San Raffaele Scientific Institute, Milan, Italy. · Department of Pathology, Marche Polytechnic University, Ancona, Italy. · Department of Gastroenterology and Pancreatology, Hopital Beaujon, Paris ENETS Center of Excellence, Clichy, France. · Department of Medical Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma-Università Cattolica del Sacro Cuore, Roma ENETS Center of Excellence, Rome, Italy. · Department of Medical Biology and Pathology, Cancer Campus, Villejuif, France. · Department of Molecular Medicine, University of Pavia, Pavia, Italy. · Pathology Department, Humanitas Clinical and Research Center, Humanitas Milan ENETS Center of Excellence, Milan, Italy. · Department of Pathology, Sacro Cuore-Don Calabria Hospital, Negrar, Italy. ·Neuroendocrinology · Pubmed #30300897.

ABSTRACT: BACKGROUND: The World Health Organization (WHO) and the American Joint Cancer Committee (AJCC) modified the grading of pancreatic neuroendocrine neoplasms from a three-tier (WHO-AJCC 2010) to a four-tier system by introducing the novel category of NET G3 (WHO-AJCC 2017). OBJECTIVES: This study aims at validating the WHO-AJCC 2017 and identifying the most effective grading system. METHOD: A total of 2,102 patients were enrolled; entry criteria were: (i) patient underwent surgery; (ii) at least 2 years of follow-up; (iii) observation time up to 2015. Data from 34 variables were collected; grading was assessed and compared for efficacy by statistical means including Kaplan-Meier method, Cox regression analysis, Harrell's C statistics, and Royston's explained variation in univariable and multivariable analyses. RESULTS: In descriptive analysis, the two grading systems demonstrated statistically significant differences for the major category sex but not for age groups. In Cox regression analysis, both grading systems showed statistically significant differences between grades for OS and EFS; however, no statistically significant difference was observed between the two G3 classes of WHO-AJCC 2017. In multivariable analysis for the two models fitted to compare efficacy, the two grading systems performed equally well with substantially similar optimal discrimination and well-explained variation for both OS and EFS. The WHO-AJCC 2017 grading system retained statistically significant difference between the two G3 classes for OS but not for EFS. CONCLUSIONS: The WHO-AJCC 2017 grading system is at least equally performing as the WHO-AJCC 2010 but allows the successful identification of the most aggressive PanNET subgroup. Grading is confirmed as probably the most powerful tool for predicting patient survival.

30 Article Endoscopic ultrasound appearance of pancreatic serotonin-staining neuroendocrine neoplasms. 2018

Massironi, Sara / Partelli, Stefano / Petrone, Maria C / Zilli, Alessandra / Conte, Dario / Falconi, Massimo / Arcidiacono, Paolo G. ·Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, 20122, Italy. Electronic address: sara.massironi@policlinico.mi.it. · Division of Pancreatic Surgery, Ospedale San Raffaele IRCCS, Università Vita-Salute San Raffaele, Milan, 20132, Italy. · Pancreato-Biliary Endoscopy and Endosonography Division, Ospedale San Raffaele IRCCS, Università Vita-Salute San Raffaele, Milan, 20132, Italy. · Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, 20122, Italy. ·Pancreatology · Pubmed #30115562.

ABSTRACT: BACKGROUND/OBJECTIVES: The pancreatic localization of serotonin-staining neuroendocrine neoplasms is extremely rare. This is a retrospective study aimed at analyzing the endoscopic ultrasound appearance of pancreatic serotoninoma. METHODS: Between 2010 and 2016, all consecutive patients with histologically proven pancreatic serotoninoma who had undergone endoscopic ultrasound were enrolled. RESULTS: Eight patients (six F, median age 68.5 years) had a diagnosis of pancreatic serotoninoma and underwent endoscopic ultrasound examinations. Median diameter of the lesion was ten mm. The nodule echotexture was hypoechoic in seven out of eight cases. The most frequent localization was the pancreatic neck (four); in three cases, the tumor was located in the pancreatic head and in one in the body. In seven cases the tumor caused a main pancreatic duct dilation; in three cases also the secondary ducts were dilated. In one case a dilation of the common bile duct was observed. At contrast-enhanced endoscopic ultrasound no one showed the typical contrast-enhancement. Elastography (available in two patients) showed a rigid pattern of the lesion. CONCLUSIONS: From this case series a specific endoscopic ultrasound appearance resulted for pancreatic serotoninoma, different from other types of pancreatic neuroendocrine neoplasm, but it is difficult to differentiate it from a pancreatic adenocarcinoma or an intraductal papillary mucinous neoplasm.

31 Article Recurrence of Pancreatic Neuroendocrine Tumors and Survival Predicted by Ki67. 2018

Genç, C G / Falconi, M / Partelli, S / Muffatti, F / van Eeden, S / Doglioni, C / Klümpen, H J / van Eijck, C H J / Nieveen van Dijkum, E J M. ·Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands. · Pancreatic Surgery Unit, Pancreas Translational and Research Institute, Scientific Institute, San Raffaele Hospital, University Vita e Salute, Milan, Italy. · Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands. · Department of Pathology, Scientific Institute, San Raffaele Hospital, University Vita e Salute, Milan, Italy. · Department of Medical Oncology, Academic Medical Center, Amsterdam, The Netherlands. · Cancer Center Amsterdam, Amsterdam, The Netherlands. · Department of Surgery, Erasmus Medical Center, Rotterdam, The Netherlands. · Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands. e.j.nieveenvandijkum@amc.uva.nl. ·Ann Surg Oncol · Pubmed #29789972.

ABSTRACT: BACKGROUND: Despite evidence of different malignant potentials, postoperative follow-up assessment is similar for G1 and G2 pancreatic neuroendocrine tumors (panNETs) and adjuvant treatment currently is not indicated. This study investigated the role of Ki67 with regard to recurrence and survival after curative resection of panNET. METHODS: Patients with resected non-functioning panNET diagnosed between 1992 and 2016 from three institutions were retrospectively analyzed. Patients who had G1 or G2 tumor without distant metastases or hereditary syndromes were included in the study. The patients were re-categorized into Ki67 0-5 and Ki67 6-20%. Cox regression analysis with log-rank testing for recurrence and survival was performed. RESULTS: The study enrolled 241 patients (86%) with Ki67 0-5% and 39 patients (14%) with Ki67 6-20%. Recurrence was seen in 34 patients (14%) with Ki67 0-5% after a median period of 34 months and in 16 patients (41%) with Ki67 6-20% after a median period of 16 months (p < 0.001). The 5-year recurrence-free and 10-year disease-specific survival periods were respectively 90 and 91% for Ki67 0-5% and respectively 55 and 26% for Ki67 6-20% (p < 0.001). The overall survival period after recurrence was 44.9 months, which was comparable between the two groups (p = 0.283). In addition to a Ki67 rate higher than 5%, tumor larger than 4 cm and lymph node metastases were independently associated with recurrence. CONCLUSIONS: Patients at high risk for recurrence after curative resection of G1 or G2 panNET can be identified by a Ki67 rate higher than 5%. These patients should be more closely monitored postoperatively to detect recurrence early and might benefit from adjuvant treatment. A clear postoperative follow-up regimen is proposed.

32 Article Impact of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR) single nucleotide polymorphisms on outcome in gastroenteropancreatic neuroendocrine neoplasms. 2018

Berardi, Rossana / Torniai, Mariangela / Partelli, Stefano / Rubini, Corrado / Pagliaretta, Silvia / Savini, Agnese / Polenta, Vanessa / Santoni, Matteo / Giampieri, Riccardo / Onorati, Sofia / Barucca, Federica / Murrone, Alberto / Bianchi, Francesca / Falconi, Massimo. ·Clinica di Oncologia Medica, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona, Ancona, Italy. · Chirurgia del Pancreas, Ospedale San Raffaele IRCCS, Università Vita e Salute, Milano, Italy. · Section of Pathological Anatomy and Histopathology, Deparment of Neuroscience, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona, Ancona, Italy. · Dipartimento di Chirurgia Generale, Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona, Ancona, Italy. ·PLoS One · Pubmed #29787601.

ABSTRACT: Angiogenesis represents a key event in cancer development, leading to local invasion e metastatization, and might be considered a basic feature in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) with a high expression of angiogenic molecules. We aimed to analyze the prognostic and predictive role of angiogenic factors in GEP-NENs through the analysis of single nucleotide polymorphisms (SNPs) of VEGF-A, VEGFR2 and VEGFR3. The genomic DNA of 58 consecutive patients with GEP-NENs treated at our Institution was extracted from peripheral blood. Two SNPs were identified respectively in VEGF-A (rs2010963G>C, rs699947A>C), VEGFR-2 (rs2305948C>T, rs1870377T>A), and VEGFR-3 (rs307821T>C, rs307826C>A) gene. Gene polymorphisms were determined by Real-Time PCR using TaqMan assays. Median age was 57 years (range 24-79 years); 32 patients were male and 77.5% of NENs were localized in the pancreas. The allele frequency of VEGFR-2 rs2305948T and of VEGF-A rs2010963C showed a trend of higher frequency than in general population (12.1% vs. 8.0% and 34.5% vs. 31.2%, respectively). Three out SNPs (VEGF-A rs699947C, VEGF-A rs2010963GC and VEGFR-3 rs307821C) showed a correlation with an increased risk of disease relapse. Moreover median PFS changes according to the presence of 0-1 SNPs (20.7% of cases; 61.9 months), 2 SNPs (25.9%; 49.2 months) and 3 SNPs (53.4%; 27.8 months) (p = 0.034). Results suggest, for the first time, that specific SNPs in VEGF-A and VEGFR-3 correlate with poor prognosis in GEP-NENs. The identification of this new prognostic factor might be helpful in order to optimize the management of these heterogeneous neoplasms.

33 Article Minimally Invasive Versus Open Treatment for Benign Sporadic Insulinoma Comparison of Short-Term and Long-Term Outcomes. 2018

Belfiori, Giulio / Wiese, Dominik / Partelli, Stefano / Wächter, Sabine / Maurer, Elisabeth / Crippa, Stefano / Falconi, Massimo / Bartsch, Detlef K. ·Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Center, Vita-Salute San Raffaele University, Milan, Italy. giulio_belfiori@live.it. · Department of Visceral, Thoracic and Vascular Surgery, Philipps University Marburg, 35041, Baldingerstrasse, Marburg, Germany. · Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Center, Vita-Salute San Raffaele University, Milan, Italy. ·World J Surg · Pubmed #29691623.

ABSTRACT: BACKGROUND: Benign insulinoma is the most common functioning neuroendocrine tumor of the pancreas, and its incidence is estimated at 0.4%. The treatment of choice is organ-preserving resection. The aim of this study was to compare short-term and long-term outcomes of minimally invasive laparoscopic or robotic enucleation (MIC-EN) and open enucleation (O-EN) for sporadic benign insulinoma. METHODS: A retrospective bi-institutional analysis of 71 patients who underwent an enucleation for sporadic benign insulinoma between 2003 and 2016 was performed. Patients were analyzed according to intention-to-treat principle. RESULTS: Fifteen (21%) patients underwent MIC-EN (three robotic and 12 laparoscopic) and 56 (79%) patients O-EN. In all MIC-EN patients, the insulinoma was localized by preoperative imaging compared to only 62.5% (35 of 56) patients in the O-EN group (p = 0.005). Three of the MIC-EN patients (20%) with insulinomas in the pancreatic head had to undergo a conversion. Excluding conversions, MIC-EN procedures were shorter (145 vs 180, p = 0.036) compared to O-EN surgery. Late complications and pathological data did not differ between groups, excluding margin status R1 MIC-EN (26.7%) compared to O-EN (10.7%, p = 0.115). After a median follow-up of 75 (range 1-151) months, all patients were alive, but four (5.6%) patients (one after MIC-EN and three after O-EN) developed a functional recurrence. No patient with a R1 resection had a disease recurrence. CONCLUSIONS: MIC-EN for benign sporadic insulinoma is a safe procedure with at least similar short-term and long-term postoperative outcomes as the open technique. Thus, preoperatively localized benign insulinoma should be approached laparoscopically, if technically feasible.

34 Article The number of positive nodes accurately predicts recurrence after pancreaticoduodenectomy for nonfunctioning neuroendocrine neoplasms. 2018

Partelli, Stefano / Javed, Ammar A / Andreasi, Valentina / He, Jin / Muffatti, Francesca / Weiss, Matthew J / Sessa, Fausto / La Rosa, Stefano / Doglioni, Claudio / Zamboni, Giuseppe / Wolfgang, Christopher L / Falconi, Massimo. ·Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, "Vita-Salute" University, Milan, Italy. · Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Medicine and Surgery, University of Insubria, Varese, Italy. · Service of Clinical Pathology, Lausanne University Hospital, Institute of Pathology, Lausanne, Switzerland. · Department of Pathology, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, "Vita-Salute" University, Milan, Italy. · Department of Pathology, Ospedale "Sacro Cuore-Don Calabria", Negrar, Italy. · Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, "Vita-Salute" University, Milan, Italy. Electronic address: falconi.massimo@hsr.it. ·Eur J Surg Oncol · Pubmed #29610023.

ABSTRACT: BACKGROUND: The most appropriate nodal staging for pancreatic neuroendocrine neoplasms (PanNENs) is unclear. Aim of the study was to evaluate the effect of the number of positive lymph nodes on prognosis after pancreaticoduodenectomy for PanNENs. METHODS: A retrospective analysis of pancreaticoduodenectomies for nonfunctioning PanNENs was performed. PanNENs with nodal metastases (N+) were classified into N1 (1 to 3 positive lymph nodes) and N2 (4 or more positive lymph nodes). Univariate and multivariate analyses of disease-free survival were performed. RESULTS: 157 patients were included. 99 patients (63%) had N0 PanNENs whereas 58 patients (37%) had nodal involvement (N+). Patients with N0 PanNENs had a 3-year disease-free survival rate of 89% compared with 83% and 75% in patients with N1 and N2 PanNENs, respectively (P < 0.0001). Independent predictors of disease-free survival were the presence of necrosis, lymph node ratio and nodal status. Factors positively correlated with the number of positive lymph nodes were the Ki67 value, the T stage and the number of examined lymph nodes. Similar percentage of N0 and N+ PanNENs was demonstrated for a cut-off of 13 examined lymph nodes. CONCLUSIONS: The number of positive lymph nodes is accurate in predicting recurrence for PanNENs. Thirteen examined lymph nodes seems to be the minimum number of lymph nodes to be resected/examined in patients who undergo pancreaticoduodenectomy for PanNENs.

35 Article Sunitinib in patients with pre-treated pancreatic neuroendocrine tumors: A real-world study. 2018

Rinzivillo, Maria / Fazio, Nicola / Pusceddu, Sara / Spallanzani, Andrea / Ibrahim, Toni / Campana, Davide / Marconcini, Riccardo / Partelli, Stefano / Badalamenti, Giuseppe / Brizzi, Maria Pia / Catena, Laura / Schinzari, Giovanni / Carnaghi, Carlo / Berardi, Rossana / Faggiano, Antongiulio / Antonuzzo, Lorenzo / Spada, Francesca / Gritti, Sara / Femia, Daniela / Gelsomino, Fabio / Bongiovanni, Alberto / Ricci, Sergio / Brighi, Nicole / Falconi, Massimo / Delle Fave, Gianfranco / Panzuto, Francesco. ·Digestive and Liver Disease, ENETS Center of Excellence Sant'Andrea Hospital - Sapienza University of Rome, Italy. · Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, ENETS Center of Excellence IEO, Milan, Italy. · Department of Medical Oncology, Fondazione IRCCS Istituto Tumori Milano, ENETS Center of Excellence, Milan, Italy. · Division of Oncology, Department of Oncology and Haematology, University Hospital of Modena, Modena, Italy. · Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. · Department of Medical and Surgical Sciences, S.Orsola-Malpighi University Hospital, Bologna, Italy. · Department of Oncology, Azienda Ospedaliero-Universitaria Pisana and University of Pisa, Istituto Toscano Tumori, Santa Chiara Hospital, Pisa, Italy. · Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Vita e Salute University, Milan, Italy. · Department of Surgical and Oncological Sciences, University of Palermo, Palermo, Italy. · Medical Oncology, AOU S. Luigi Gonzaga Regione Gonzole 10, Orbassano, Italy. · Struttura di Oncologia Policlinico di Monza, Monza, MB, Italy. · Medical Oncology, Università Cattolica del Sacro Cuore, Rome, Italy. · Oncology Unit, Humanitas Clinical and Research Centre, Rozzano, Italy. · Medical Oncology, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I, Ancona, Italy. · Divisione di Endocrinologia, Dipartimento di Medicina Clinica e Chirurgia, Università di Napoli Federico II, ENETS Center of Excellence Naples, Italy. · S.C di Oncologia Medica, AOU Careggi Florence, Italy. · Department of Experimental, Diagnostic and Specialty Medicine, S.Orsola-Malpighi University Hospital, Bologna, Italy. · Digestive and Liver Disease, ENETS Center of Excellence Sant'Andrea Hospital - Sapienza University of Rome, Italy. Electronic address: fpanzuto@ospedalesantandrea.it. ·Pancreatology · Pubmed #29361429.

ABSTRACT: INTRODUCTION: Besides data reported in a Phase-III trial, data on sunitinib in pancreatic Neuroendocrine Tumors (panNETs) are scanty. AIM: To evaluate sunitinib efficacy and tolerability in panNETs patients treated in a real-world setting. PATIENTS AND METHODS: Retrospective analysis of progressive panNETs treated with sunitinib. Efficacy was assessed by evaluating progression-free survival, overall survival, and disease control (DC) rate (stable disease (SD) + partial response + complete response). Data are reported as median (25th-75th IQR). RESULTS: Eighty patients were included. Overall, 71.1% had NET G2, 26.3% had NET G1, and 2.6% had NET G3 neoplasms. A total of 53 patients (66.3%) had received three or more therapeutic regimens before sunitinib, with 24 patients (30%) having been treated with four previous treatments. Median PFS was 10 months. Similar risk of progression was observed between NET G1 and NET G2 tumors (median PFS 11 months and 8 months, respectively), and between patients who had received ≥ 3 vs ≤ 2 therapeutic approaches before sunitinib (median PFS 9 months and 10 months, respectively). DC rate was 71.3% and SD was the most frequent observed response, occurring in 43 pts (53.8%). Overall, 59 pts (73.8%) experienced AEs, which were grade 1-2 in 43 of them (72.9%), grade 3 in 15 pts (25.4%), and grade 4 in one patient (1.7%). Six pts (7.5%) stopped treatment due to toxicity. CONCLUSIONS: The present real-world experience shows that sunitinib is a safe and effective treatment for panNETs, even in the clinical setting of heavily pre-treated, progressive diseases.

36 Article Peptide receptor radionuclide therapy as neoadjuvant therapy for resectable or potentially resectable pancreatic neuroendocrine neoplasms. 2018

Partelli, Stefano / Bertani, Emilio / Bartolomei, Mirco / Perali, Carolina / Muffatti, Francesca / Grana, Chiara Maria / Schiavo Lena, Marco / Doglioni, Claudio / Crippa, Stefano / Fazio, Nicola / Zamboni, Giuseppe / Falconi, Massimo. ·Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, "Vita-Salute" University, Milan, Italy. · Surgery Department, European Institute of Oncology, Milan, Italy. · Nuclear Medicine Department, "S. Anna" Hospital, Ferrara, Italy. · Nuclear Medicine Department, European Institute of Oncology, Milan, Italy. · Pathology Department, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, "Vita-Salute" University, Milan, Italy. · Oncology Department, European Institute of Oncology, Milan, Italy. · Pathology Department, "Sacro Cuore-Don Calabria" Hospital, Negrar, Italy. · Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, "Vita-Salute" University, Milan, Italy. Electronic address: falconi.massimo@hsr.it. ·Surgery · Pubmed #29284590.

ABSTRACT: BACKGROUND: Peptide receptor radionuclide therapy is a valid therapeutic option for pancreatic neuroendocrine neoplasms. The aim of this study was to describe an initial experience with the use of peptide receptor radionuclide therapy as a neoadjuvant agent for resectable or potentially resectable pancreatic neuroendocrine neoplasms. METHODS: The postoperative outcomes of 23 patients with resectable or potentially resectable pancreatic neuroendocrine neoplasms at high risk of recurrence who underwent neoadjuvant peptide receptor radionuclide therapy (peptide receptor radionuclide therapy group) were compared with 23 patients who underwent upfront surgical operation (upfront surgery group). Patients were matched for tumor size, grade, and stage. Median follow-up was 61 months. RESULTS: The size (median greatest width) of the primary pancreatic neuroendocrine neoplasms decreased after neoadjuvant peptide receptor radionuclide therapy (59 to 50 mm; P=.047). There were no differences in intraoperative and postoperative outcomes and there were no operative deaths, but the risk of developing a pancreatic fistula tended to be less in the peptide receptor radionuclide therapy group when compared to the upfront surgery group (0/23 vs 4/23; P < .02). The incidence of nodal metastases at the time of resection was also less in the peptide receptor radionuclide therapy group (n= 9/23 vs 17/23; P<.02). Neither median disease-specific survival (not reached in either group; P=.411) nor progression-free survival (52 vs 37 months; P>.2) differed between groups, but progression-free survival in the 31 patients who had an R0 resection seemed to be greater in the 15 patients in the peptide receptor radionuclide therapy group versus 16 patients the upfront group (median progression-free survival not reached vs 36 months; P<.05). CONCLUSION: Neoadjuvant peptide receptor radionuclide therapy for resectable or potentially resectable pancreatic neuroendocrine neoplasms in patients with high-risk features of recurrence seems to be beneficial, but well-designed and much larger prospective trials are needed to confirm the safety and the oncologic value of this approach.

37 Article A Systematic review and meta-analysis on the role of palliative primary resection for pancreatic neuroendocrine neoplasm with liver metastases. 2018

Partelli, Stefano / Cirocchi, Roberto / Rancoita, Paola M V / Muffatti, Francesca / Andreasi, Valentina / Crippa, Stefano / Tamburrino, Domenico / Falconi, Massimo. ·Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, "Vita-Salute" University, Milan, Italy. · Department of Digestive and Liver Surgery Unit, St Maria Hospital, Terni, Italy. · University Centre for Statistics in the Biomedical Sciences, "Vita-Salute" University, Milan, Italy. · Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, "Vita-Salute" University, Milan, Italy; Digestive Oncology PhD Program, La Sapienza University, Rome, Italy. · Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, "Vita-Salute" University, Milan, Italy. Electronic address: falconi.massimo@hsr.it. ·HPB (Oxford) · Pubmed #29196022.

ABSTRACT: BACKGROUND: Role of palliative pancreatic neuroendocrine neoplasm (PanNEN) resection (pPanNEN-R) is controversial. This study was designed as a meta-analysis of studies which allow a comparison of pPanNEN-R and non-surgical management (PanNEN-nR). METHODS: All published studies until 2017 allowing for the comparison of pPanNEN-R and PanNEN-nR were reviewed. Primary outcome was overall survival (OS). Secondary outcomes measures included postoperative morbidity, reoperation, readmission, length of hospital stay (LOS), and quality of life (QoL). Risk of death was compared by computing the odds-ratio (OR), while 5- and 10-year OS using weighted mean differences. RESULTS: Seven studies were included. A total of 885 patients were included, of whom 252 (28%) underwent pPanNEN-R and 633 (72%) underwent PanNEN-nR. Overall quality of included studies was fair. The risk of death was significantly reduced in patients who underwent pPanNEN-R compared to those who underwent PanNEN-nR (OR = 0.38, 95% CI 0.23-0.65). Data on postoperative morbidity, reoperation, readmission, LOS, and QoL were not adequately reported therefore a meta-analysis for the secondary outcomes was not performed. DISCUSSION: pPanNEN-R in patients with unresectable LM seems to be associated with a better OS compared to non-surgical management but the limitations of included studies does not allow firm conclusions.

38 Article Clinical Usefulness of 2018

Rinzivillo, Maria / Partelli, Stefano / Prosperi, Daniela / Capurso, Gabriele / Pizzichini, Patrizia / Iannicelli, Elsa / Merola, Elettra / Muffatti, Francesca / Scopinaro, Francesco / Schillaci, Orazio / Salgarello, Matteo / Falconi, Massimo / Delle Fave, Gianfranco / Panzuto, Francesco. ·Digestive and Liver Disease Unit, ENETS Center of Excellence, Sapienza University of Rome, Rome, Italy. · Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Vita e Salute University, Milan, Italy. · Department of Nuclear Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy. · Department of Radiology, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy. · Department of Nuclear Medicine, University of Tor Vergata, Rome, Italy. · Department of Nuclear Medicine, Ospedale Sacro Cuore Don Calabria, Negrar, Italy. · Digestive and Liver Disease Unit, ENETS Center of Excellence, Sapienza University of Rome, Rome, Italy fpanzuto@ospedalesantandrea.it. ·Oncologist · Pubmed #29118267.

ABSTRACT: BACKGROUND: The role of RESULTS: A total of 93 patients, including 69 patients with pancreatic NENs and 24 patients with small-intestine NENs, were included. At the time of study entry, 64 patients (68.8%) had PD, and the remaining 29 patients (31.2%) had SD. A total of 62 patients (66.7%) had positive IMPLICATIONS FOR PRACTICE: The findings of the present study may help physicians dealing with advanced neuroendocrine neoplasms to select patients for whom

39 Article SUVmax after (18)fluoro-deoxyglucose positron emission tomography/computed tomography: A tool to define treatment strategies in pancreatic cancer. 2018

Pergolini, Ilaria / Crippa, Stefano / Salgarello, Matteo / Belfiori, Giulio / Partelli, Stefano / Ruffo, Giacomo / Pucci, Alessandro / Zamboni, Giuseppe / Falconi, Massimo. ·Department of Surgery, Universita' Politecnica delle Marche, Ancona, Italy. · Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy. · Department of Nuclear Medicine, Ospedale Sacro Cuore-Don Calabria, Negrar, Italy. · Department of Surgery, Ospedale Sacro Cuore-Don Calabria, Negrar, Italy. · Department of Pathology, Ospedale Sacro Cuore-Don Calabria, Negrar, Italy. · Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy. Electronic address: falconi.massimo@hsr.it. ·Dig Liver Dis · Pubmed #29017830.

ABSTRACT: BACKGROUND: (18)fluoro-deoxyglucose positron emission tomography/computed tomography (18FDG-PET/CT) might be a useful tool in the management of pancreatic ductal adenocarcinoma (PDAC). AIMS: The aim of this study was to analyze maximum standard uptake value (SUVmax) after 18FDG-PET/CT as predictor of survival outcomes and method to determine treatment strategies. METHODS: A consecutive series of patients who underwent preoperative 18FDG-PET/CT and subsequent resection for PDAC were retrospectively reviewed. Patients who underwent neoadjuvant chemotherapy were excluded. RESULTS: 46 patients were included in the analysis. Median follow-up was 27 months (4-67). Patients who recurred within 12 months showed a significantly higher preoperative median SUVmax (8.1 vs 6.1, p=0.039). Receiver operating characteristics (ROC) curves for disease-free survival (DFS) and disease-specific survival (DSS) identified SUVmax of 6.0 as optimal cut-off. Multivariate analysis showed that SUVmax ≥ 6.0 was an independent predictor of poor DFS (HR 2.288, p=0.024) and DSS (HR 4.875, p<0.001). The combination of SUVmax ≥6.0 with CA19.9 ≥200U/ml was significantly associated with survival outcomes in comparison to patients without concordantly elevated values. CONCLUSION: SUVmax ≥6.0 is an independent predictor of DFS and DSS in resected PDAC. 18FDG-PET/CT might be considered in the preoperative evaluation of patients with pancreatic cancer.

40 Article Prognosis of sporadic resected small (≤2 cm) nonfunctional pancreatic neuroendocrine tumors - a multi-institutional study. 2018

Sallinen, Ville J / Le Large, Tessa Y S / Tieftrunk, Elke / Galeev, Shamil / Kovalenko, Zahar / Haugvik, Sven-Petter / Antila, Anne / Franklin, Oskar / Martinez-Moneo, Emma / Robinson, Stuart M / Panzuto, Francesco / Regenet, Nicolas / Muffatti, Francesca / Partelli, Stefano / Wiese, Dominik / Ruszniewski, Philippe / Dousset, Bertrand / Edwin, Bjørn / Bartsch, Detlef K / Sauvanet, Alain / Falconi, Massimo / Ceyhan, Güralp O / Gaujoux, Sebastien / Anonymous100922. ·Department of Abdominal Surgery, Helsinki University Hospital, University of Helsinki, Helsinki, Finland; Department of Transplantation and Liver Surgery, Helsinki University Hospital, University of Helsinki, Helsinki, Finland. Electronic address: ville.salinen@helsinki.fi. · Department of Surgery, VU University Medical Center, Amsterdam, The Netherlands. · Department of Surgery, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany. · General Surgery Department, Saint Luke's Clinical Hospital, Saint Petersburg, Russia. · Federal Medical and Rehabilitation Center, Department of Surgical Oncology, Moscow, Russia. · The Intervention Center, Oslo University Hospital, Oslo, Norway; Department of Surgery, Drammen Hospital, Vestre Viken Hospital Trust, Drammen, Norway. · Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland. · Department of Surgical and Perioperative Sciences, Umea University, Umea, Sweden. · Gastroenterology Department, Hospital Universitario Cruces, Barakaldo, Bizkaia, Spain. · Department of HPB Surgery, Freeman Hospital, Newcastle Upon Tyne, UK. · Digestive and Liver Disease Unit, Sant'Andrea Hospital - Sapienza University of Rome, Italy. · Department of Digestive and Endocrine Surgery, Institut des Maladies Digestives (IMAD), Nantes 44093, France. · Chirurgia Del Pancreas, Chirurgia Del Pancreas, Pancreas Translational & Clinical Research Center, Università Vita e Salute, Ospedale San Raffaele IRCC, Milano, Italy. · Department of Visceral, Thoracic and Vascular Surgery, Philipps University Marburg, Marburg, Germany. · Department of Gastroenterology, Pôle des Maladies de L'Appareil Digestif (PMAD), DHU Unity, Clichy 92110, France; Université Paris Diderot, Paris, France. · Department of Digestive, Pancreatic and Endocrine Surgery, Cochin Hospital, APHP, Paris, France; Faculté de Médecine Paris Descartes, Université Paris Descartes, Sorbonne Paris Cité, Paris, France. · The Intervention Center, Oslo University Hospital, Oslo, Norway; Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway. · Université Paris Diderot, Paris, France; AP-HP, Hôpital Beaujon, Department of Hepato-Pancreato-Biliary Surgery, Pôle des Maladies de L'Appareil Digestif (PMAD), DHU Unity, University Paris VII, AP-HP, Hôpital Beaujon, Clichy 92110, France. ·HPB (Oxford) · Pubmed #28988702.

ABSTRACT: BACKGROUND: Malignant potential of small (≤20 mm) nonfunctional pancreatic neuroendocrine tumors (sNF-PNET) is difficult to predict and management remain controversial. The aim of this study was to assess the prognosis of sporadic nonmetastatic sNF-PNETs. METHODS: Patients were identified from databases of 16 centers. Outcomes and risk factors for recurrence were identified by uni- and multivariate analyses. RESULTS: sNF-PNET was resected in 210 patients, and 66% (n = 138) were asymptomatic. Median age was 60 years, median tumor size was 15 mm, parenchyma-sparing surgery was performed in 42%. Postoperative mortality was 0.5% (n = 1), severe morbidity rate was 14.3% (n = 30), and 14 of 132 patients (10.6%) with harvested lymph nodes had metastatic lymph nodes. Tumor size, presence of biliary or pancreatic duct dilatation, and WHO grade 2-3 were independently associated with recurrence. Patients with tumors sized ≤10 mm were disease free at last follow-up. The 1-, 3- and 5-year disease-free survival rates for patients with tumors sized 11-20 mm on preoperative imaging were 95.1%, 91.0%, and 87.3%, respectively. CONCLUSIONS: In sNF-PNETs, the presence of biliary or pancreatic duct dilatation or WHO grade 2-3 advocate for surgical treatment. In the remaining patients, a wait-and-see policy might be considered.

41 Article A New Scoring System to Predict Recurrent Disease in Grade 1 and 2 Nonfunctional Pancreatic Neuroendocrine Tumors. 2018

Genç, Cansu G / Jilesen, Anneke P / Partelli, Stefano / Falconi, Massimo / Muffatti, Francesca / van Kemenade, Folkert J / van Eeden, Susanne / Verheij, Joanne / van Dieren, Susan / van Eijck, Casper H J / Nieveen van Dijkum, Elisabeth J M. ·Department of Surgery, Academic Medical Center, Amsterdam, the Netherlands. · Pancreatic Surgery Unit, Pancreas Translational & Research Institute, Scientific Institute San Raffaelle Hospital & University Vita e Salute, Milano, Italy. · Department of Pathology, Erasmus Medical Center, Rotterdam, the Netherlands. · Department of Pathology, Academic Medical Center, Amsterdam, the Netherlands. · Department of Methodology and Statistic CRU, Academic Medical Center, Amsterdam, the Netherlands. · Department of Surgery, Erasmus Medical Center, Rotterdam, the Netherlands. ·Ann Surg · Pubmed #28594340.

ABSTRACT: OBJECTIVE: The aim of this study was to predict recurrence in patients with grade 1 or 2 nonfunctioning pancreatic neuroendocrine tumors (NF-pNET) after curative resection. BACKGROUND: Surgical resection is the preferred treatment for NF-pNET; however, recurrence occurs frequently after curative surgery, worsening prognosis of patients. METHODS: Retrospectively, patients with NF-pNET of 3 institutions were included. Patients with distant metastases, hereditary syndromes, or grade 3 tumors were excluded. Local or distant tumor recurrence was scored. Independent predictors for survival and recurrence were identified using Cox-regression analysis. The recurrence score was developed to predict recurrence within 5 years after curative resection of grade 1 to 2 NF-pNET. RESULTS: With a median follow-up of 51 months, 211 patients with grade 1 to 2 NF-pNET were included. Thirty-five patients (17%) developed recurrence. The 5- and 10-year disease-specific/overall survival was 98%/91% and 84%/68%, respectively. Predictors for recurrence were tumor grade 2, lymph node metastasis, and perineural invasion. On the basis of these predictors, the recurrence score was made. Discrimination [c-statistic 0.81, 95% confidence interval (95% CI) 0.75-0.87] and calibration (Hosmer Lemeshow Chi-square 11.25, P = 0.258) indicated that the ability of the recurrence score to identify patients at risk for recurrence is good. CONCLUSIONS: This new scoring system could predict recurrence after curative resection of grade 1 and 2 NF-pNET. With the use of the recurrence score, less extensive follow-up could be proposed for patients with low recurrence risk. For high-risk patients, clinical trials should be initiated to investigate whether adjuvant therapy might be beneficial. External validation is ongoing due to limited availability of adequate cohorts.

42 Article Impact of Ki67 re-assessment at time of disease progression in patients with pancreatic neuroendocrine neoplasms. 2017

Panzuto, Francesco / Cicchese, Noemi / Partelli, Stefano / Rinzivillo, Maria / Capurso, Gabriele / Merola, Elettra / Manzoni, Marco / Pucci, Eugenio / Iannicelli, Elsa / Pilozzi, Emanuela / Rossi, Michele / Doglioni, Claudio / Falconi, Massimo / Delle Fave, Gianfranco. ·Digestive and Liver Disease Unit, Sant'Andrea Hospital Sapienza University of Rome, Roma, Italy. · Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, "Vita-Salute" University, Milan, Italy. · Department of Endocrinology and Internal Medicine, San Raffaele Hospital Scientific Institute, Milan, Italy. · Department of Experimental Medicine and Pathology, Sant'Andrea Hospital Sapienza University of Rome, Roma, Italy. · Department of Radiology, Sant'Andrea Hospital Sapienza University of Rome, Roma, Italy. · Department of Pathology, San Raffaele Scientific Institute, "Vita-Salute" University, Milan, Italy. ·PLoS One · Pubmed #28644861.

ABSTRACT: BACKGROUND: Although re-assessment of proliferative activity by K67 evaluation during the course of neuroendocrine neoplasms (NENs) is recommended in selected patients, its impact on patients' management is not clear due to the lack of data supporting this practice. AIM: To investigate Ki67 change at time of progressive disease (PD) in entero-pancreatic NENs (EP-NENs). PATIENTS AND METHODS: Retrospective analysis of sporadic EP-NENs which received histological re-assessment after PD once radiologically documented. RESULTS: Forty-three patients were evaluated, including 24 pancreatic NENs (PNENs), and 19 small intestine NENs (SI-NENs). At time of initial histological evaluation, 19 patients had grade 1 (G1) NETs (44.2%), and 24 grade 2 (G2) NETs (55.8%), overall median Ki67 being 3% (range 1%-20%). At time of PD, 13 patients had G1 NETs (30.2%), 26 G2 NETs (60.5%), and 4 had grade 3 (G3) NECs (9.3%), thus resulting in a significant median Ki67 increase (8%, range 1%-70%; p = 0.0006), and a G upgrading in 12 patients (27.9%). A statistically significant Ki67 increase and G grading change at time of PD was observed in PNENs (p = 0.0005 and p = 0.028, respectively). Conversely, no statistically significant change occurred in non-PNENs. CONCLUSIONS: In PNENs with documented PD, Ki67 increase occurs in a significant proportion of patients, providing useful information necessary to choose appropriate therapeutic options.

43 Article Prognostic impact of the cumulative dose and dose intensity of everolimus in patients with pancreatic neuroendocrine tumors. 2017

Berardi, Rossana / Torniai, Mariangela / Pusceddu, Sara / Spada, Francesca / Ibrahim, Toni / Brizzi, Maria Pia / Antonuzzo, Lorenzo / Ferolla, Piero / Panzuto, Francesco / Silvestris, Nicola / Partelli, Stefano / Ferretti, Benedetta / Freddari, Federica / Gucciardino, Calogero / Testa, Enrica / Concas, Laura / Murgioni, Sabina / Bongiovanni, Alberto / Zichi, Clizia / Riva, Nada / Rinzivillo, Maria / Brunetti, Oronzo / Giustini, Lucio / Di Costanzo, Francesco / Delle Fave, Gianfranco / Fazio, Nicola / De Braud, Filippo / Falconi, Massimo / Cascinu, Stefano. ·Clinica di Oncologia Medica, Università Politecnica delle Marche, AOU Ospedali Riuniti di, Ancona, Italy. · Medicina Oncologica 1, ENETS Center of excellence, Fondazione IRCCS Istituto Tumori, Milano, Italy. · Unità di Oncologia Medica Gastrointestinale e Tumori Neuroendocrini (Unit of Gastrointestinal Medical Oncology and Neuroendocrine Tumors), IEO Istituto Europeo di Oncologia, Milano, Italy. · Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. · Oncologia Medica, A.O.U. San Luigi, Orbassano (TO), Italy. · SC di Oncologia Medica, Azienda Opedaliero-Universitaria Careggi, Firenze, Italy. · Doctorate Course in Genetics, Oncology and Clinical Medicine, University of Siena, Siena, Italy. · Multidisciplinary NET Group, Umbria Regional Cancer Network, Perugia, Italy. · Digestive and Liver Disease, Sapienza University of Rome, Sant'Andrea Hospital, Rome, Italy. · Medical Oncology Unit, National Cancer Institute Giovanni Paolo II, Bari, Italy. · Chirurgia del Pancreas, Università Politecnica delle Marche, AOU Ospedali Riuniti di, Ancona, Italy. · Chirurgia del Pancreas, Ospedale San Raffaele IRCCS, Università Vita e Salute, Milano, Italy. · Oncologia Medica, Ospedale di San Severino, San Severino Marche (MC), Italy. · Oncologia Medica, Ospedale di Senigallia, Senigallia, Italy. · Oncologia Medica, Ospedale di Fermo, Fermo, Italy. · Oncologia Medica, Ospedale di Urbino, Urbino, Italy. · Oncologia Medica, Università di Modena e Reggio Emilia, Modena, Italy. ·Cancer Med · Pubmed #28547856.

ABSTRACT: The aim of this work is to assess if cumulative dose (CD) and dose intensity (DI) of everolimus may affect survival of advanced pancreatic neuroendocrine tumors (PNETs) patients. One hundred and sixteen patients (62 males and 54 females, median age 55 years) with advanced PNETs were treated with everolimus for ≥3 months. According to a Receiver operating characteristics (ROC) analysis, patients were stratified into two groups, with CD ≤ 3000 mg (Group A; n = 68) and CD > 3000 mg (Group B; n = 48). The response rate and toxicity were comparable in the two groups. However, patients in group A experienced more dose modifications than patients in group B. Median OS was 24 months in Group A while in Group B it was not reached (HR: 26.9; 95% CI: 11.0-76.7; P < 0.0001). Patients who maintained a DI higher than 9 mg/day experienced a significantly longer OS and experienced a trend to higher response rate. Overall, our study results showed that both CD and DI of everolimus play a prognostic role for patients with advanced PNETs treated with everolimus. This should prompt efforts to continue everolimus administration in responsive patients up to at least 3000 mg despite delays or temporary interruptions.

44 Article Functional Imaging in the Follow-Up of Enteropancreatic Neuroendocrine Tumors: Clinical Usefulness and Indications. 2017

Merola, Elettra / Pavel, Marianne E / Panzuto, Francesco / Capurso, Gabriele / Cicchese, Noemi / Rinke, Anja / Gress, Thomas M / Iannicelli, Elsa / Prosperi, Daniela / Pizzichini, Patrizia / Prasad, Vikas / Kump, Patrizia / Lipp, Rainer / Partelli, Stefano / Falconi, Massimo / Wiedenmann, Bertram / Delle Fave, Gianfranco. ·Digestive and Liver Diseases Unit, Sant'Andrea Hospital, 00189 Rome, Italy. · Department of Hepatology and Gastroenterology, Charité Universitätsmedizin, 13353 Berlin, Germany. · Department of Gastroenterology, University Hospital, 35043 Marburg, Germany. · Department of Radiology, Sant'Andrea Hospital, 00189 Rome, Italy. · Division of Nuclear Medicine, Sant'Andrea Hospital, 00189 Rome, Italy. · Department of Nuclear Medicine, Campus Virchow-Klinikum, Charité Universitätsmedizin, 13353 Berlin, Germany. · Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University, 8036 Graz Austria. · Division of Nuclear Medicine, Department of Radiology, Medical University, 8036 Graz Austria. · Pancreatic Surgery Unit, Vita-Salute University, San Raffaele Hospital Istituto di Ricovero e Cura a Carattere Scientifico, 20132 Milan, Italy. ·J Clin Endocrinol Metab · Pubmed #28324047.

ABSTRACT: Context: Functional imaging tests (FITs) detecting somatostatin receptor expression [i.e., somatostatin receptor scintigraphy, 68Ga-DOTA positron emission tomography/computed tomography (CT)] have a pivotal role in the diagnosis of neuroendocrine tumors (NETs), although their indication during follow-up still needs to be clarified. Objective: Investigate the role of FITs after diagnosis of metastatic enteropancreatic NETs, identifying patients who might benefit from these exams. Design: Multicenter retrospective analysis of metastatic enteropancreatic NETs. Setting: Analysis of imaging tests performed between January 1995 and December 2015 in Rome, Berlin, Milan, Marburg, or Graz. Subjects: One hundred forty-three patients with metastatic pancreatic NETs and small intestine NETs, at least 2-year follow-up, and positive FITs. Interventions: Patients had received CT every 6 months (unless clinical conditions and tumor behavior required shorter intervals) and FIT every 12 months. Main Outcome Measures: Clinical usefulness of FITs, defined as changes in patient management (indication to biopsy, medical therapy, surgery, or further imaging tests) due only to FITs. Results: FITs affected management in 73.4% of patients, mostly when G2 vs G1 [odds ratio (OR), 2.40; 95% confidence interval (CI), 1.09 to 5.27; P = 0.03]. Changes were observed in a 12-month time frame especially with pancreatic NETs vs small intestine NETs (OR, 2.89; 95% CI, 1.09 - 7.67; P = 0.03) or metastases since diagnosis vs developed during follow-up (OR, 4.00; 95% CI, 1.43 to 11.17; P < 0.01). Conclusions: FITs used in addition to CT in the follow-up of stage IV enteropancreatic NETs improve patient management (especially for G2 tumors). Follow-up program should be tailored according to tumor features.

45 Article Stage IV Gastro-Entero-Pancreatic Neuroendocrine Neoplasms: A Risk Score to Predict Clinical Outcome. 2017

Panzuto, Francesco / Merola, Elettra / Pavel, Marianne Ellen / Rinke, Anja / Kump, Patrizia / Partelli, Stefano / Rinzivillo, Maria / Rodriguez-Laval, Victor / Pape, Ulrich Frank / Lipp, Rainer / Gress, Thomas / Wiedenmann, Bertram / Falconi, Massimo / Delle Fave, Gianfranco. ·Department of Digestive and Liver Disease, Sapienza University of Rome - Sant'Andrea Hospital, Rome, Italy. · Department of Hepatology and Gastroenterology, Charité Campus Mitte and Virchow Clinic, Charité University Medicine, Berlin, Germany. · Department of Gastroenterology, Philipps-University of Marburg, Germany. · Clinical Division of Gastroenterology, Medical University Graz, Austria. · Division of Pancreatic Surgery, Vita-Salute University, San Raffaele Scientific Institute, Milan, Italy. · Department of Radiology Charité University, Campus Virchow Klinikum, Berlin, Germany. · Clinical Division of Oncology, Medical University Graz, Austria. · Department of Digestive and Liver Disease, Sapienza University of Rome - Sant'Andrea Hospital, Rome, Italy gianfranco.dellefave@uniroma1.it. ·Oncologist · Pubmed #28232598.

ABSTRACT: BACKGROUND: Several risk factors predict clinical outcome in gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs); however, the impact of their combination has not been investigated so far. PATIENTS AND METHODS: A retrospective analysis of stage IV GEP-NENs was performed. Multivariate analysis for progression of disease (PD) was performed by Cox proportional hazards method to obtain a risk score. Area under the curve obtained by receiver operating characteristic analysis was used to assess the score performance. Progression-free survival analysis was performed by Kaplan-Meier method. RESULTS: Two hundred eighty-three stage IV GEP-NENs were evaluated, including 93 grade 1 neuroendocrine tumors (32.9%), 153 grade 2 neuroendocrine tumors (54%), and 37 grade 3 neuroendocrine carcinomas (13.1%). Independent risk factors for PD were Ki67, proportion of metastatic liver involvement, and presence of extra-abdominal metastases. The risk score was calculated as follows: (0.025 × Ki67) + [(0 if no liver metastases or liver involvement <25%) OR (0.405 if liver involvement 25%-50%) OR (0.462 if liver involvement >50%)] + [(0 if no extra-abdominal metastases) OR (0.528 if extra-abdominal metastases present)]. The risk score accuracy to predict PD was superior compared with the G grading system (area under the curve: 0.705 and 0.622, respectively). Three subgroups of patients with low, intermediate, and high risk of PD according to risk score were identified, median progression-free survival being 26 months, 19 months, and 12 months, respectively. CONCLUSION: In stage IV GEP-NENs, a risk score able to predict PD was obtained by combining Ki67, proportion of metastatic liver involvement, and presence of extra-abdominal metastases. The score may help to discriminate patients with different progression risk level to plan tailored therapeutic approaches and follow-up programs.

46 Article Whole-genome landscape of pancreatic neuroendocrine tumours. 2017

Scarpa, Aldo / Chang, David K / Nones, Katia / Corbo, Vincenzo / Patch, Ann-Marie / Bailey, Peter / Lawlor, Rita T / Johns, Amber L / Miller, David K / Mafficini, Andrea / Rusev, Borislav / Scardoni, Maria / Antonello, Davide / Barbi, Stefano / Sikora, Katarzyna O / Cingarlini, Sara / Vicentini, Caterina / McKay, Skye / Quinn, Michael C J / Bruxner, Timothy J C / Christ, Angelika N / Harliwong, Ivon / Idrisoglu, Senel / McLean, Suzanne / Nourse, Craig / Nourbakhsh, Ehsan / Wilson, Peter J / Anderson, Matthew J / Fink, J Lynn / Newell, Felicity / Waddell, Nick / Holmes, Oliver / Kazakoff, Stephen H / Leonard, Conrad / Wood, Scott / Xu, Qinying / Nagaraj, Shivashankar Hiriyur / Amato, Eliana / Dalai, Irene / Bersani, Samantha / Cataldo, Ivana / Dei Tos, Angelo P / Capelli, Paola / Davì, Maria Vittoria / Landoni, Luca / Malpaga, Anna / Miotto, Marco / Whitehall, Vicki L J / Leggett, Barbara A / Harris, Janelle L / Harris, Jonathan / Jones, Marc D / Humphris, Jeremy / Chantrill, Lorraine A / Chin, Venessa / Nagrial, Adnan M / Pajic, Marina / Scarlett, Christopher J / Pinho, Andreia / Rooman, Ilse / Toon, Christopher / Wu, Jianmin / Pinese, Mark / Cowley, Mark / Barbour, Andrew / Mawson, Amanda / Humphrey, Emily S / Colvin, Emily K / Chou, Angela / Lovell, Jessica A / Jamieson, Nigel B / Duthie, Fraser / Gingras, Marie-Claude / Fisher, William E / Dagg, Rebecca A / Lau, Loretta M S / Lee, Michael / Pickett, Hilda A / Reddel, Roger R / Samra, Jaswinder S / Kench, James G / Merrett, Neil D / Epari, Krishna / Nguyen, Nam Q / Zeps, Nikolajs / Falconi, Massimo / Simbolo, Michele / Butturini, Giovanni / Van Buren, George / Partelli, Stefano / Fassan, Matteo / Anonymous6880896 / Khanna, Kum Kum / Gill, Anthony J / Wheeler, David A / Gibbs, Richard A / Musgrove, Elizabeth A / Bassi, Claudio / Tortora, Giampaolo / Pederzoli, Paolo / Pearson, John V / Waddell, Nicola / Biankin, Andrew V / Grimmond, Sean M. ·ARC-Net Centre for Applied Research on Cancer, University and Hospital Trust of Verona, Verona 37134, Italy. · Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona 37134, Italy. · Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1QH, UK. · West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow G31 2ER, UK. · The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research, University of New South Wales, 384 Victoria St, Darlinghurst, Sydney, New South Wales 2010, Australia. · Department of Surgery, Bankstown Hospital, Eldridge Road, Bankstown, Sydney, New South Wales 2200, Australia. · South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Liverpool, New South Wales 2170, Australia. · QIMR Berghofer Medical Research Institute, Herston Road, Brisbane 4006, Australia. · Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia. · Department of Surgery, Pancreas Institute, University and Hospital Trust of Verona, Verona 37134, Italy. · Medical Oncology, University and Hospital Trust of Verona, Verona, Italy. · Department of Pathology, General Hospital of Treviso, Department of Medicine, University of Padua, Italy. · Department of Medicine, Section of Endocrinology, University and Hospital Trust of Verona, Verona, Italy. · The University of Queensland, School of Medicine, Brisbane 4006, Australia. · Pathology Queensland, Brisbane 4006, Australia. · Royal Brisbane and Women's Hospital, Department of Gastroenterology and Hepatology, Brisbane 4006, Australia. · Institute of Health Biomedical Innovation, Queensland University of Technology, Brisbane, Australia. · School of Environmental &Life Sciences, University of Newcastle, Ourimbah, New South Wales 2258, Australia. · Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Centre for Cancer Bioinformatics, Peking University Cancer Hospital &Institute, Beijing 100142, China. · Department of Surgery, Princess Alexandra Hospital, Ipswich Rd, Woollongabba, Queensland 4102, Australia. · Department of Anatomical Pathology. St Vincent's Hospital, Sydney, New South Wales 2010, Australia. · Academic Unit of Surgery, School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow Royal Infirmary, Glasgow G4 OSF, UK. · Department of Pathology, Queen Elizabeth University Hospital, Greater Glasgow &Clyde NHS, Glasgow G51 4TF, UK. · Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, One Baylor Plaza, MS226, Houston, Texas 77030-3411, USA. · Michael E. DeBakey Department of Surgery and The Elkins Pancreas Center, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030-3411, USA. · Children's Hospital at Westmead, Westmead, New South Wales 2145, Australia. · Children's Medical Research Institute, The University of Sydney, Westmead, New South Wales 2145, Australia. · Department of Surgery, Royal North Shore Hospital, St Leonards, Sydney, New South Wales 2065, Australia. · University of Sydney. Sydney, New South Wales 2006, Australia. · Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, New South Wales 2050, Australia. · School of Medicine, Western Sydney University, Penrith, New South Wales 2175, Australia. · Department of Surgery, Fremantle Hospital, Alma Street, Fremantle, Western Australia 6160, Australia. · Department of Gastroenterology, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia 5000, Australia. · School of Surgery M507, University of Western Australia, 35 Stirling Highway, Nedlands, Western Australia 6009, Australia. · St John of God Pathology, 12 Salvado Rd, Subiaco, Western Australia 6008, Australia. · Bendat Family Comprehensive Cancer Centre, St John of God Subiaco Hospital, Subiaco, Western Australia 6008, Australia. · University of Melbourne Centre for Cancer Research, University of Melbourne, Melbourne, 3010, Victoria, Australia. ·Nature · Pubmed #28199314.

ABSTRACT: The diagnosis of pancreatic neuroendocrine tumours (PanNETs) is increasing owing to more sensitive detection methods, and this increase is creating challenges for clinical management. We performed whole-genome sequencing of 102 primary PanNETs and defined the genomic events that characterize their pathogenesis. Here we describe the mutational signatures they harbour, including a deficiency in G:C > T:A base excision repair due to inactivation of MUTYH, which encodes a DNA glycosylase. Clinically sporadic PanNETs contain a larger-than-expected proportion of germline mutations, including previously unreported mutations in the DNA repair genes MUTYH, CHEK2 and BRCA2. Together with mutations in MEN1 and VHL, these mutations occur in 17% of patients. Somatic mutations, including point mutations and gene fusions, were commonly found in genes involved in four main pathways: chromatin remodelling, DNA damage repair, activation of mTOR signalling (including previously undescribed EWSR1 gene fusions), and telomere maintenance. In addition, our gene expression analyses identified a subgroup of tumours associated with hypoxia and HIF signalling.

47 Article Assessing the role of primary tumour resection in patients with synchronous unresectable liver metastases from pancreatic neuroendocrine tumour of the body and tail. A propensity score survival evaluation. 2017

Bertani, E / Fazio, N / Radice, D / Zardini, C / Spinoglio, G / Chiappa, A / Ribero, D / Biffi, R / Partelli, S / Falconi, M. ·Division of Hepatobilio-Pancreatic Surgery, European Institute of Oncology, Italy. Electronic address: emilio.bertani@ieo.it. · Gastrointestinal Medical Oncology and Neuroendocrine Tumours Unit, European Institute of Oncology, Milano, Italy. · Division of Epidemiology and Biostatistics, European Institute of Oncology, Milano, Italy. · Department of Surgery, Ospedale Sacro Cuore Don Calabria, Negrar, Italy. · Division of Hepatobilio-Pancreatic Surgery, European Institute of Oncology, Italy. · Division of Digestive Surgery, European Institute of Oncology, Università Statale di Milano, Milano, Italy. · Division of Pancreatic Surgery, Ospedale San Raffaele IRCCS, Università Vita e Salute, Milano, Italy. ·Eur J Surg Oncol · Pubmed #27742480.

ABSTRACT: BACKGROUND: The role of primary tumour surgery in pancreatic neuroendocrine tumours (PNETs) with unresectable liver metastases is controversial and international guidelines do not recommend surgery in such cases. Resectability of the primary tumour has never been considered in outcome comparisons between operated and non-operated patients. METHODS: From two institutional prospective databases of patients affected by PNET and unresectable liver metastases, 63 patients who underwent a left-pancreatectomy at diagnosis were identified and compared with a group of 30 patients with a potentially resectable but not-resected primary tumour located in the body or tail. The endpoint was overall survival (OS). RESULTS: The two groups significantly differed at baseline with regard to liver tumour burden Ki-67 labelling index, site of pancreas, results of the CONCLUSION: In PNETs located in the body or tail and diffuse liver metastases distal pancreatectomy may be justified in selected patients. Randomized studies may be safely proposed in future on this topic.

48 Article Low progression of intraductal papillary mucinous neoplasms with worrisome features and high-risk stigmata undergoing non-operative management: a mid-term follow-up analysis. 2017

Crippa, Stefano / Bassi, Claudio / Salvia, Roberto / Malleo, Giuseppe / Marchegiani, Giovanni / Rebours, Vinciane / Levy, Philippe / Partelli, Stefano / Suleiman, Shadeah L / Banks, Peter A / Ahmed, Nazir / Chari, Suresh T / Fernández-Del Castillo, Carlos / Falconi, Massimo. ·Division of Pancreatic Surgery, Università Politecnica delle Marche, Ancona, Italy. · Division of Pancreatic Surgery, Università Vita-Salute, San Raffaele Scientific Institute, Milan, Italy. · Unit of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy. · Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. · Service de Gastroenterologie-Pancreatologie, Hopital Beaujon, APHP, Université Paris Diderot, DHU UNITY, Clichy, France. · Center for Pancreatic Disease, Brigham and Woman's Hospital, Harvard Medical School, Boston, Massachusetts, USA. · Division of Gastroenterology, Mayo Clinic, Rochester, Minnesota, USA. ·Gut · Pubmed #26743012.

ABSTRACT: OBJECTIVE: To evaluate mid-term outcomes and predictors of survival in non-operated patients with pancreatic intraductal papillary mucinous neoplasms (IPMNs) with worrisome features or high-risk stigmata as defined by International Consensus Guidelines for IPMN. Reasons for non-surgical options were physicians' recommendation, patient personal choice or comorbidities precluding surgery. METHODS: In this retrospective, multicentre analysis, IPMNs were classified as branch duct (BD) and main duct (MD), the latter including mixed IPMNs. Univariate and multivariate analysis for overall survival (OS) and disease-specific survival (DSS) were obtained. RESULTS: Of 281 patients identified, 159 (57%) had BD-IPMNs and 122 (43%) had MD-IPMNs; 50 (18%) had high-risk stigmata and 231 (82%) had worrisome features. Median follow-up was 51 months. The 5-year OS and DSS for the entire cohort were 81% and 89.9%. An invasive pancreatic malignancy developed in 34 patients (12%); 31 had invasive IPMNs (11%) and 3 had IPMN-distinct pancreatic ductal adenocarcinoma (1%). Independent predictors of poor DSS in the entire cohort were age >70 years, atypical/malignant cyst fluid cytology, jaundice and MD >15 mm. Compared with MD-IPMNs, BD-IPMNs had significantly better 5-year OS (86% vs 74.1%, p=0.002) and DSS (97% vs 81.2%, p<0.0001). Patients with worrisome features had better 5-year DSS compared with those with high-risk stigmata (96.2% vs 60.2%, p<0.0001). CONCLUSIONS: In elderly patients with IPMNs that have worrisome features, the 5-year DSS is 96%, suggesting that conservative management is appropriate. By contrast, presence of high-risk stigmata is associated with a 40% risk of IPMN-related death, reinforcing that surgical resection should be offered to fit patients.

49 Article mTOR inhibitors response and mTOR pathway in pancreatic neuroendocrine tumors. 2016

Falletta, Simona / Partelli, Stefano / Rubini, Corrado / Nann, Dominik / Doria, Andrea / Marinoni, Ilaria / Polenta, Vanessa / Di Pasquale, Carmelina / Degli Uberti, Ettore / Perren, Aurel / Falconi, Massimo / Zatelli, Maria Chiara. ·Department of Medical ScienceSection of Endocrinology and Internal Medicine, University of Ferrara, Ferrara, Italy. · Pancreatic Surgery UnitPancreas Translational and Research Institute, San Raffaele Hospital, Vita-Salute San Raffaele University, Milan, Italy. · Department of Biomedical Sciences and Public HealthPolytechnic University of Marche, Ancona, Italy. · Institut fur PathologieUniversity of Bern, Bern, Switzerland. · Department of Medical ScienceSection of Endocrinology and Internal Medicine, University of Ferrara, Ferrara, Italy ztlmch@unife.it. ·Endocr Relat Cancer · Pubmed #27697900.

ABSTRACT: Medical therapy of pancreatic neuroendocrine tumors (P-NET) may take advantage of Everolimus treatment. However, the extent of therapeutic response cannot be predicted. This study was aimed to identify the possible predictive markers of response to Everolimus in P-NET. We found that Everolimus reduced the cell viability and induced apoptosis in primary cultures of 6 P-NET (P-NET-R), where the proliferative and antiapoptotic effects of IGF1 were blocked by Everolimus. On the contrary, 14 P-NET primary cultures (P-NET-NR) were resistant to Everolimus and IGF1, suggesting an involvement of PI3K/AKT/mTOR pathway in the mechanism of resistance. The response to Everolimus in vitro was associated with an active AKT/mTOR pathway and seemed to be associated with a greater clinical aggressiveness. In addition, a patient sensitive to Everolimus in vitro was sensitive to this drug in vivo also and showed a positive p-AKT immunohistochemistry (IHC) at tissue level. Similarly, a patient resistant to Everolimus treatment after surgery was not sensitive to the drug in vitro and had a negative p-AKT IHC staining. Therefore, present data confirm that P-NET primary cultures may be considered a model for testing medical treatment efficacy and that IHC characterization of p-AKT might help in identifying human P-NET who can benefit from Everolimus treatment. These data encourage conducting a prospective multicenter study involving different groups of P-NET patients treated with Everolimus.

50 Article Resection of the Primary Tumor Followed by Peptide Receptor Radionuclide Therapy as Upfront Strategy for the Treatment of G1-G2 Pancreatic Neuroendocrine Tumors with Unresectable Liver Metastases. 2016

Bertani, Emilio / Fazio, Nicola / Radice, Davide / Zardini, Claudio / Grana, Chiara / Bodei, Lisa / Funicelli, Luigi / Ferrari, Carlo / Spada, Francesca / Partelli, Stefano / Falconi, Massimo. ·Division of Hepatobilio-pancreatic Surgery, European Institute of Oncology, Milan, Italy. emilio.bertani@ieo.it. · GI and Neuroendocrine Tumors Unit, European Institute of Oncology, Milan, Italy. · Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy. · Surgical Department, Sacro Cuore Hospital, Negrar, Italy. · Division of Nuclear Medicine, European Institute of Oncology, Milan, Italy. · Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, USA. · Division of Radiology, European Institute of Oncology, Milan, Italy. · Division of Digestive Surgery, European Institute of Oncology, Milan, Italy. · Division of Pancreatic Surgery, Ospedale San Raffaele IRCCS, Università Vita e Salute, Milan, Italy. ·Ann Surg Oncol · Pubmed #27613553.

ABSTRACT: BACKGROUND: A low burden of disease represents an independent favorable prognostic factor of response to peptide receptor radionuclide therapy (PRRT) in patients affected by gastro-entero-pancreatic neuroendocrine tumors. However, it is not clear whether this is due to a lower diffusion of the disease or thanks to debulking surgery. METHODS: From 1996 to 2013 those patients diagnosed with G1-G2 pancreatic neuroendocrine tumor (PNET) and synchronous liver metastases who were not deemed eligible for liver radical surgery but were eligible to receive upfront PRRT were prospectively included in the study. Two groups of comparison were identified: those submitted for primary tumor resection before PRRT and those who were not. The outcome was evaluated as: objective response to PRRT (OR), progression-free survival (PFS), and overall survival (OS). RESULTS: Of the 94 subjects, 31 were previously submitted for primary tumor resection. After propensity score adjustments, patients who underwent surgery before PRRT showed higher stabilization or objective responses after PRRT (p = .006), and this translated into a better median PFS (70 vs. 30 months; p = .002) and OS (112 vs. 65 months; p = .011), for operated versus nonoperated patients, respectively. At multivariate analysis, operated patients showed a statistically significantly improved PFS: HR, 5.11 (95 % CI 1.43-18.3); p = .012, whereas Ki-67 in continuous fashion was correlated significantly with OS: 1.13 (95 % CI 1-1.27); p = .048. CONCLUSIONS: Primary tumor resection prior to PRRT can be safely proposed in G1-G2 PNETs with diffuse liver metastases because it seems to enhance response to PRRT and to improve significantly PFS.

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