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Pancreatic Neoplasms: HELP
Articles by Dr. M Falconi
Based on 20 articles published since 2010
(Why 20 articles?)

Between 2010 and 2020, M. Falconi wrote the following 20 articles about Pancreatic Neoplasms.
+ Citations + Abstracts
1 Guideline ENETS Consensus Guidelines Update for the Management of Patients with Functional Pancreatic Neuroendocrine Tumors and Non-Functional Pancreatic Neuroendocrine Tumors. 2016

Falconi, M / Eriksson, B / Kaltsas, G / Bartsch, D K / Capdevila, J / Caplin, M / Kos-Kudla, B / Kwekkeboom, D / Rindi, G / Klöppel, G / Reed, N / Kianmanesh, R / Jensen, R T / Anonymous1140854. · ·Neuroendocrinology · Pubmed #26742109.

ABSTRACT: -- No abstract --

2 Guideline Pancreatic cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. 2010

Cascinu, S / Falconi, M / Valentini, V / Jelic, S / Anonymous3370663. ·Department of Medical Oncology, Università Politecnica delle Marche, Ancona, Italy. ·Ann Oncol · Pubmed #20555103.

ABSTRACT: -- No abstract --

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

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

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

4 Review Systematic review of active surveillance versus surgical management of asymptomatic small non-functioning pancreatic neuroendocrine neoplasms. 2017

Partelli, S / Cirocchi, R / Crippa, S / Cardinali, L / Fendrich, V / Bartsch, D K / Falconi, M. ·Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Centre, San Raffaele Scientific Institute, 'Vita-Salute' University, Milan, Italy. · Department of Digestive and Liver Surgery Unit, St Maria Hospital, Terni, Italy. · Department of Surgery, Polytechnic University of Marche Region, Ancona, Italy. · Department of Visceral, Thoracic and Vascular Surgery, Philipps-University Marburg, Marburg, Germany. ·Br J Surg · Pubmed #27706803.

ABSTRACT: BACKGROUND: The incidence of asymptomatic, sporadic, small non-functioning pancreatic neuroendocrine neoplasms (NF-PNENs) has increased in recent decades. Conservative treatment has been advocated for these tumours. The aim of this study was systematically to evaluate the literature on active surveillance and to compare this with surgical management for asymptomatic sporadic small NF-PNENs. METHODS: PubMed, Embase and the Cochrane Library were searched systematically for studies that compared the active surveillance of asymptomatic, sporadic, small NF-PNENs with surgical management. PRISMA guidelines for systematic reviews were followed. RESULTS: After screening 3915 records, five retrospective studies with a total of 540 patients were included. Of these, 327 patients (60·6 per cent) underwent active surveillance and 213 (39·4 per cent) had surgery. There was wide variation in the tumour diameter threshold considered as inclusion criterion (2 cm to any size). The median length of follow-up ranged from 28 to 45 months. Measurable tumour growth was observed in 0-51·0 per cent of patients. Overall, 46 patients (14·1 per cent) underwent pancreatic resection after initial conservative treatment. In most patients the reason was an increase in tumour size (19 of 46). There were no disease-related deaths in the active surveillance group in any of the studies. CONCLUSION: This systematic review suggests that active surveillance of patients affected by sporadic, small, asymptomatic NF-PNENs may be a good alternative to surgical treatment.

5 Review Systematic review and meta-analysis of metal versus plastic stents for preoperative biliary drainage in resectable periampullary or pancreatic head tumors. 2016

Crippa, S / Cirocchi, R / Partelli, S / Petrone, M C / Muffatti, F / Renzi, C / Falconi, M / Arcidiacono, P G. ·Division of Pancreatic Surgery, Vita e Salute University, San Raffaele Scientific Institute, Milan, Italy. · Department of General and Oncologic Surgery, University of Perugia, St. Maria Hospital, Terni, Italy. · Division of Pancreato-Biliary Endoscopy and Endoscopic Ultrasound, San Raffaele Scientific Institute, Milan, Italy. · Department of General and Oncologic Surgery, University of Perugia, Perugia, Italy. · Division of Pancreatic Surgery, Vita e Salute University, San Raffaele Scientific Institute, Milan, Italy. Electronic address: falconi.massimo@hsr.it. ·Eur J Surg Oncol · Pubmed #27296728.

ABSTRACT: BACKGROUND: Preoperative biliary drainage (PBD) with stenting increases complications compared with surgery without PBD. Metallic stents are considered superior to plastic stents when considering stent-related complications. Aim of the present systematic review and meta-analysis is to compare the rate of endoscopic re-intervention before surgery and postoperative outcomes of metal versus plastic stents in patients with resectable periampullary or pancreatic head neoplasms. METHODS: We conducted a bibliographic research using the National Library of Medicine's PubMed database, including both randomized controlled trials (RCTs) and non-RCTs. Quantitative synthesis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Statistical heterogeneity was assessed using the I(2) tests. RESULTS: One RCT and four non-RCTs were selected, including 704 patients. Of these, 202 patients (29.5%) were treated with metal stents and 502 (70.5%) with plastic stents. The majority of patients (86.4%) had pancreatic cancer. The rate of endoscopic re-intervention after preoperative biliary drainage was significantly lower in the metal stent (3.4%) than in the plastic stent (14.8%) group (p < 0.0001). The rate of postoperative pancreatic fistula was significantly lower in the meta stent group as well (5.1% versus 11.8%, p = 0.04). The rate of post-operative surgical complications and of - post-operative mortality did not differ between the two groups. CONCLUSIONS: Although the present systematic review and meta-analysis demonstrates that metal stent are more effective than plastic stents for PBD in patients with resectable periampullary tumors, randomized controlled trials are needed in order to confirm these data with a higher level of evidence.

6 Review Molecular targeted therapy in enteropancreatic neuroendocrine tumors: from biology to clinical practice. 2014

Fazio, N / Scarpa, A / Falconi, M. ·Unit of Gastrointestinal and Neuroendocrine Tumor, European Institute of Oncology, Via Ripamonti 435 20141 Milan, Italy. nicola.fazio@ieo.it. ·Curr Med Chem · Pubmed #23992320.

ABSTRACT: Advanced enteropancreatic (EP) neuroendocrine tumors (NETs) can be treated with several different therapies, including chemotherapy, biotherapy, and locoregional treatments. Over the last few decades, impressive progress has been made in the biotherapy field. Three main druggable molecular targets have been studied and developed in terms of therapy: somatostatin receptor (sstr), mammalian target of rapamycin (mTOR), and angiogenic factors. In particular, research has moved from the old somatostatin analogs (SSAs), such as octreotide (OCT) and lanreotide (LAN), specifically binding to the sstr-2, to the newer pasireotide (PAS), which presents a wider sstr spectrum. Over the last ten years, several molecular targeted agents (MTAs) have been studied in phase II trials, and very few of them have reached phase III. The mTOR inhibitor everolimus and the multitargeted inhibitor sunitinib have been approved for clinical use by the FDA and EMA in advanced well/moderately-differentiated (WD, MD) progressive pancreatic neuroendocrine tumors (PNETs), on the basis of the positive results of two international large randomized phase III trials vs. placebo. Bevacizumab has been studied in a large US phase III trial vs. interferon (IFN)-alfa2b, and results are pending. In this review, the biological and clinical aspects of MTAs introduced into clinical practice or which are currently in an advanced phase of clinical investigation are addressed.

7 Review Imaging of neuroendocrine gastroenteropancreatic tumours. 2010

Graziani, R / Brandalise, A / Bellotti, M / Manfredi, R / Contro, A / Falconi, M / Boninsegna, L / Pozzi Mucelli, R. ·Dipartimento di Scienze Morfologico-Biomediche, Policlinico G.B. Rossi, Istituto di Radiologia, Verona, Italy. graziani.rossella@azosp.univr.it ·Radiol Med · Pubmed #20221711.

ABSTRACT: The role of imaging in functioning endocrine tumours (FETs) is primarily to detect the tumour, that is, to verify lesion number and location. Radiological detection of carcinoid tumours is limited by typical tumour location throughout the gastrointestinal tract or appendix and is therefore dependent on the tumour being large enough to make it recognisable in that site. The most common FET is insulinoma, which is commonly characterised by the typical appearance of a hypervascular lesion at multidetector-row computed tomography and magnetic resonance imaging. A particularly important role is played by intraoperative ultrasound in defining the exact number of lesions, their relationship with adjacent vascular structures and the pancreatic duct for the purposes of correct surgical planning (enucleation or resection). In the setting of nonfunctioning endocrine tumours (NFETs), which manifest late as large masses causing compression symptoms or as incidental findings, imaging is not primarily aimed at tumour detection, as this is relatively easy given the large size of the lesions. Rather, its role is to characterise the tumour and, in particular, to differentiate pancreatic NFET from ductal adenocarcinoma, as in comparison, malignant NFETs have a more favourable prognosis (5-year survival rate 40% compared with 3%-5% for adenocarcinoma) and therefore require different treatment approaches. As NFET are often malignant, they also require accurate staging and appropriate follow-up. In 80% of cases, NFETs have a "typical" imaging appearance: location in the pancreatic head, large dimensions (diameter between 5 and 15 cm, >10 cm in 30% of cases), capsule, sharp and regular margins owing to the expansile and noninfiltrative growth pattern, solid density and arterial hypervascularity. Some 20% of NFETs display different imaging characteristics ("atypical" appearance) as a result of arterial hypovascularity due to the presence of abundant fibrous stroma. Lastly, a small percentage of NFETs has yet a different appearance ("unusual") due to the cystic nature and/or diffuse location throughout the pancreatic parenchyma.

8 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.

9 Article Selecting patients for resection after primary chemotherapy for non-metastatic pancreatic adenocarcinoma. 2017

Reni, M / Zanon, S / Balzano, G / Nobile, S / Pircher, C C / Chiaravalli, M / Passoni, P / Arcidiacono, P G / Nicoletti, R / Crippa, S / Slim, N / Doglioni, C / Falconi, M / Gianni, L. ·Department of Oncology. · Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center. · Department of Radiotherapy. · Department of Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS. · Department of Radiology. · Department of Pathology, Pancreas Translational & Clinical Research Center, IRCCS Ospedale San Raffaele, Milan. · Department of Vita-Salute San Raffaele University, Milan, Italy. ·Ann Oncol · Pubmed #28945895.

ABSTRACT: Background: Patients with borderline (BL) or locally advanced (LA) pancreatic adenocarcinoma are usually treated with primary chemotherapy (CT), followed by resection when feasible. Scanty data are available about the criteria to candidate patients to resection after CT. Patients and methods: Between 2002 and 2016 overall 223 patients diagnosed with BL or LA pancreatic adenocarcinoma were primarily treated with Gemcitabine combination (4-drugs or nab-paclitaxel-gemcitabine) for 3-6 months followed by surgery and/or chemoradiation. Resection was carried out when radical resection could be predicted by imaging studies and intraoperative findings. The prognostic value of both pre-treatment factors and treatment response was retrospectively evaluated, searching for criteria that could improve the selection of patients for surgery. Results: Median survival (MS) for the whole population was 18.3 months. Surgical resection was carried out in 61 patients; MS in resected patients was significantly longer (30.0 months) as compared with 162 non-resected patients (16.5 months) (P < 0.00001). According to response criteria, 48% had a radiological partial response, 47% a stable disease and 5% a disease progression); CA19.9 response (reduction >50%) was obtained in 77.8% of patients. Among resected patients, neither pre-treatment factors, including BL/LA distinction, nor radiological response, were able to prognosticate survival differences. Survival of resected patients having no CA19.9 response was significantly lower as compared with responders (MS 15.0 versus 31.5 months, P = 0.04), and was similar to non-responders patients that did not undergo resection (MS 10.9 months, P= 0.25). Multivariate analysis carried out on the overall population, showed that Karnofsky performance status, T3-T4 status, resection and CA19.9 response were independent prognostic factors, while radiological response, BL/LA distinction and baseline CA19.9 had not significant influence on survival. Conclusions: CA19.9 response may allow a better selection of patients who will benefit from resection after primary CT for BL or LA pancreatic adenocarcinoma.

10 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.

11 Article Is there a role for surgical resection in patients with pancreatic cancer with liver metastases responding to chemotherapy? 2016

Crippa, S / Bittoni, A / Sebastiani, E / Partelli, S / Zanon, S / Lanese, A / Andrikou, K / Muffatti, F / Balzano, G / Reni, M / Cascinu, S / Falconi, M. ·Department of Surgery, IRCCS Ospedale San Raffaele, Vita-Salute University, Milan, Italy. · Department of Oncology, Ospedali Riuniti, Università Politecnica delle Marche, Ancona, Italy. · Department of Surgery, Ospedali Riuniti, Università Politecnica delle Marche, Ancona, Italy. · Department of Oncology, IRCCS Ospedale San Raffaele, Vita-Salute University, Milan, Italy. · Department of Surgery, IRCCS Ospedale San Raffaele, Vita-Salute University, Milan, Italy. Electronic address: falconi.massimo@hsr.it. ·Eur J Surg Oncol · Pubmed #27423449.

ABSTRACT: BACKGROUND: New chemotherapeutic regimens have improved survival for stage IV pancreatic ductal adenocarcinoma and occasionally major response of liver metastases can be observed. Aim of this work is to analyze the outcomes of patients undergoing primary chemotherapy for liver metastases from pancreatic cancer and to evaluate the results of surgical resection. METHODS: Retrospective analysis. EXCLUSION CRITERIA: patients with extra-hepatic metastases, patients with Eastern Cooperative Oncology Group performance status ≥3, patients undergoing supportive care alone. RESULTS: 127 patients were identified. Liver metastases were unilobar in 28.5% of patients. Chemotherapy regimens included gemcitabine alone or in association with other agents (44%), oxaliplatin, irinotecan, fluorouracil and leucovorin (FOLFIRINOX 8%), and cisplatin, gemcitabine plus capecitabine and epirubicin (PEXG) or capecitabine and docetaxel (PDXG) or epirubicin and fluorouracil (PEFG) (48%). 56 patients (44%) had a complete (7%) or partial response (37%). surgical resection was carried out in 11 patients (8.5%). Median overall survival was 11 months for the entire cohort and 15 months for those with partial/complete response. In this sub-group median survival was significantly longer (46 versus 11 months) for patients undergoing resection (P < 0.0001). Independent predictors of overall survival were chemotherapy with multiple agents (HR: 0.512), surgical resection (HR: 0.360), >5 liver metastases at diagnosis (HR: 3.515), and CA 19.9 reduction < 50% of baseline value (HR: 2.708). CONCLUSIONS: Surgical resection of primary pancreatic tumor with or without residual liver disease can be considered in selected cases after primary chemotherapy and it is associated with improved survival.

12 Article Intraductal papillary mucinous neoplasms of the pancreas with concurrent pancreatic and periampullary neoplasms. 2016

Sahora, K / Crippa, S / Zamboni, G / Ferrone, C / Warshaw, A L / Lillemoe, K / Mino-Kenudson, M / Falconi, M / Fernandez-del Castillo, C. ·Department of Surgery, Massachusetts General Hospital, Boston, USA; Department of Pathology, Massachusetts General Hospital, Boston, USA. · Department of Surgery, Ospedale Sacro Cuore Don Calabria, Negrar (VR), Italy; Department of Pathology, Ospedale Sacro Cuore Don Calabria, Negrar (VR), Italy. · Department of Pathology, Ospedale Sacro Cuore Don Calabria, Negrar (VR), Italy. · Department of Pathology, Massachusetts General Hospital, Boston, USA. · Department of Surgery, Massachusetts General Hospital, Boston, USA; Department of Pathology, Massachusetts General Hospital, Boston, USA. Electronic address: cfernandez@partners.org. ·Eur J Surg Oncol · Pubmed #26687069.

ABSTRACT: BACKGROUND: Intraductal papillary mucinous neoplasms (IPMN) have been reported to be associated with concurrent, distinct pancreatic ductal adenocarcinoma (con-PDAC) in about 8% (range, 4-10%) of resected branch duct (BD) lesions. In addition, other pancreatic and ampullary tumors are occasionally diagnosed with IPMN in patients undergoing pancreatic surgery. The objective of this study is to describe the prevalence, clinicopathologic characteristics and prognosis of IPMN with concurrent pancreatic and ampullary neoplasms, especially con-PDAC. METHODS: The combined databases of pancreatic resections from the Massachusetts General Hospital and the Negrar Hospital, Italy, were analyzed for patients who had been diagnosed with IPMN and concurrent pancreatic or ampullary neoplasms. RESULTS: 2762 patients underwent pancreatic surgery from January 2000 to December 2012. Sixteen percent (n = 441) had pathologically confirmed IPMN and 11% of these (n = 50) had a different distinct synchronous pancreatic neoplasm. The majority of these, 62%, were con-PDAC, followed by neuroendocrine neoplasms (10%) and ampullary carcinoma (10%). Less frequently, mucinous (6%) as well as serous cystic neoplasms (6%), adenosquamous carcinoma (4%) and distal bile duct cancer (2%) were diagnosed. Among all patients with synchronous neoplasms, 66% harbored BD-IPMN, 28% combined IPMN and 6% main duct IPMN. Abdominal pain and/or jaundice were the leading symptoms in half of patients. CONCLUSION: IPMN, mainly BD-IPMN, are associated with con-PDAC in about 7% of patients and account for 62% of all concurrent pancreatic/ampullary neoplasms. Other synchronous neoplasms may be found sporadically with IPMN without a suspected association.

13 Article Serous cystic neoplasm of the pancreas: a multinational study of 2622 patients under the auspices of the International Association of Pancreatology and European Pancreatic Club (European Study Group on Cystic Tumors of the Pancreas). 2016

Jais, B / Rebours, V / Malleo, G / Salvia, R / Fontana, M / Maggino, L / Bassi, C / Manfredi, R / Moran, R / Lennon, A M / Zaheer, A / Wolfgang, C / Hruban, R / Marchegiani, G / Fernández Del Castillo, C / Brugge, W / Ha, Y / Kim, M H / Oh, D / Hirai, I / Kimura, W / Jang, J Y / Kim, S W / Jung, W / Kang, H / Song, S Y / Kang, C M / Lee, W J / Crippa, S / Falconi, M / Gomatos, I / Neoptolemos, J / Milanetto, A C / Sperti, C / Ricci, C / Casadei, R / Bissolati, M / Balzano, G / Frigerio, I / Girelli, R / Delhaye, M / Bernier, B / Wang, H / Jang, K T / Song, D H / Huggett, M T / Oppong, K W / Pererva, L / Kopchak, K V / Del Chiaro, M / Segersvard, R / Lee, L S / Conwell, D / Osvaldt, A / Campos, V / Aguero Garcete, G / Napoleon, B / Matsumoto, I / Shinzeki, M / Bolado, F / Fernandez, J M Urman / Keane, M G / Pereira, S P / Acuna, I Araujo / Vaquero, E C / Angiolini, M R / Zerbi, A / Tang, J / Leong, R W / Faccinetto, A / Morana, G / Petrone, M C / Arcidiacono, P G / Moon, J H / Choi, H J / Gill, R S / Pavey, D / Ouaïssi, M / Sastre, B / Spandre, M / De Angelis, C G / Rios-Vives, M A / Concepcion-Martin, M / Ikeura, T / Okazaki, K / Frulloni, L / Messina, O / Lévy, P. ·Department of Gastroenterology and Pancreatology, Beaujon Hospital, AP-HP, Clichy, France. · The Pancreas Institute, G.B. Rossi Hospital, University of Verona Hospital Trust, Verona, Italy. · Division of Gastroenterology and Hepatology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA Division of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. · Departments of Surgery and Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. · Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. · First Department of Surgery, Yamagata University Faculty of Medicine, Yamagata, Japan. · Department of Surgery, Seoul National University College of Medicine, Seoul, Korea. · Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea. · Department of Surgery, Yonsei University College of Medicine, Pancreaticobiliary Cancer Clinic, Yonsei Cancer Center, Severance Hospital, Seoul, Korea. · Pancreatic Surgery Unit, Department of Surgery, Polytechnic University of Marche Region, Ancona-Torrette, Italy. · NIHR Pancreas Biomedical Research Unit, Department of Molecular and Clinical Cancer Medicine, Royal Liverpool University Hospital, Institute of Translational Medicine, University of Liverpool, Liverpool, UK. · Department of Surgery, Oncology and Gastroenterology, 3rd Surgical Clinic, University of Padua, Padua, Italy. · Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum-University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy. · Pancreatic Surgery Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy. · Hepato-Pancreato-Biliary Unit, Pederzoli Hospital, Peschiera del Garda, Italy. · Department of Gastroenterology, Hepatopancreatology and GI Oncology, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium. · Institute of Hepatopancreatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China. · Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. · Department of Pathology, Gyeongsang National University School of Medicine, Jinju, Korea. · Hepato-Pancreato-Biliary Unit, Freeman Hospital, Newcastle upon Tyne, UK. · National Institute of Surgery and Transplantology named after Shalimov, Kiev, Ukraine. · Division of Surgery, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet at Center for Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden. · Division of Gastroenterology, Brigham and Women's Hospital, Boston, Massachusetts, USA. · Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. · Hôpital Privé Mermoz, Gastroentérologie, Lyon, France. · Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan. · Gastroenterology Department, Hospital de Navarra, Pamplona, Spain. · Department of Gastroenterology and Hepatology, University College Hospital, London, UK. · Department of Gastroenterology, Hospital Clinic, CIBEREHD, IDIBAPS, University of Barcelona, Barcelona, Spain. · Department of Pancreatic Surgery, Humanitas Research Hospital, Rozzano, Milan, Italy. · Gastroenterology and Liver Services, Concord Hospital, Sydney, New South Wales, Australia. · Radiological Department, General Hospital Cá Foncello, Treviso, Italy. · Division of Gastroenterology and Gastrointestinal Endoscopy, San Raffaele Scientific Institute, Milan, Italy. · Department of Internal Medicine, Digestive Disease Center and Research Institute, SoonChunHyang University School of Medicine, Bucheon, Korea. · Department of Gastroenterology, Bankstown-Lidcombe Hospital, Bankstown, New South Wales, Australia. · Department of Digestive Surgery, Timone Hospital, Marseille, France. · Gastrohepatology Department, San Giovanni Battista Molinette Hospital, University of Turin, Turin, Italy. · Gastroenterology Department, Hospital de la Santa Creu i Sant Pau, Institut de Reçerca-IIB Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain. · The Third Department of Internal Medicine, Division of Gastroenterology and Hepatology, Kansai Medical University, Osaka, Japan. · Department of Medicine, Pancreas Center, University of Verona, Verona, Italy. ·Gut · Pubmed #26045140.

ABSTRACT: OBJECTIVES: Serous cystic neoplasm (SCN) is a cystic neoplasm of the pancreas whose natural history is poorly known. The purpose of the study was to attempt to describe the natural history of SCN, including the specific mortality. DESIGN: Retrospective multinational study including SCN diagnosed between 1990 and 2014. RESULTS: 2622 patients were included. Seventy-four per cent were women, and median age at diagnosis was 58 years (16-99). Patients presented with non-specific abdominal pain (27%), pancreaticobiliary symptoms (9%), diabetes mellitus (5%), other symptoms (4%) and/or were asymptomatic (61%). Fifty-two per cent of patients were operated on during the first year after diagnosis (median size: 40 mm (2-200)), 9% had resection beyond 1 year of follow-up (3 years (1-20), size at diagnosis: 25 mm (4-140)) and 39% had no surgery (3.6 years (1-23), 25.5 mm (1-200)). Surgical indications were (not exclusive) uncertain diagnosis (60%), symptoms (23%), size increase (12%), large size (6%) and adjacent organ compression (5%). In patients followed beyond 1 year (n=1271), size increased in 37% (growth rate: 4 mm/year), was stable in 57% and decreased in 6%. Three serous cystadenocarcinomas were recorded. Postoperative mortality was 0.6% (n=10), and SCN's related mortality was 0.1% (n=1). CONCLUSIONS: After a 3-year follow-up, clinical relevant symptoms occurred in a very small proportion of patients and size slowly increased in less than half. Surgical treatment should be proposed only for diagnosis remaining uncertain after complete workup, significant and related symptoms or exceptionally when exists concern with malignancy. This study supports an initial conservative management in the majority of patients with SCN. TRIAL REGISTRATION NUMBER: IRB 00006477.

14 Article Presentation, diagnostic features and glucose handling in a monocentric series of insulinomas. 2013

Toaiari, M / Davì, M V / Dalle Carbonare, L / Boninsegna, L / Castellani, C / Falconi, M / Francia, G. ·Department of Internal Medicine D, "G.B. Rossi" University Hospital, Verona, Italy. ·J Endocrinol Invest · Pubmed #23608735.

ABSTRACT: BACKGROUND: New aspects have emerged in the clinical and diagnostic scenarios of insulinoma: current guidelines have lowered the diagnostic insulin threshold to 3 μU/ml in the presence of hypoglycemia (<55 mg/dl); post-prandial hypoglycemia has been reported as the only presenting symptom; preexisting diabetes mellitus (DM) was recognized in some patients. AIM: To evaluate clinical features, diagnostic criteria and glucose metabolic profile in a monocentric series of patients affected by insulinomas including two subgroups: sporadic and multiple endocrine neoplasia type-1 syndrome (MEN-1). SUBJECTS AND METHODS: Clinical, pathological and biochemical data regarding 33 patients were analyzed. RESULTS: following the current guidelines the 72-h fasting test was initially positive in all cases but one. In this case the test, initially negative, became positive after a 2-yr follow-up. Nadir insulin level was ≥ 3 μU/ml but <6 μU/ml in 3 patients and ≥ 6 μU/ml in the remaining 30 cases. At presentation, 27 patients (82%) reported only fasting symptoms, 3 (9%) only post-prandial and 3 (9%) both. Seven cases (21%) had previously been affected by type 2 DM or impaired glucose metabolism. CONCLUSIONS: In our series the new cut-off of insulin increased the sensitivity of the 72-h fasting test from 87% to 97%. The absence of hypoglycemia during the test cannot definitively rule out the diagnosis and the test should be repeated in every highly suspicious case. Post-prandial hypoglycemia can be the only presenting symptom. DM may be associated with the occurrence of insulinoma. So that a possible diagnosis of insulinoma must not be ignored if previous impaired glucose handling is evident.

15 Article Perfusion CT can predict tumoral grading of pancreatic adenocarcinoma. 2013

D'Onofrio, M / Gallotti, A / Mantovani, W / Crosara, S / Manfrin, E / Falconi, M / Ventriglia, A / Zamboni, G A / Manfredi, R / Pozzi Mucelli, R. ·Department of Radiology, University Hospital G.B. Rossi Piazzale L.A. Scuro 10, 37134 University of Verona, Verona, Italy. mirko.donofrio@univr.it ·Eur J Radiol · Pubmed #23127804.

ABSTRACT: OBJECTIVES: To describe perfusion CT features of locally advanced pancreatic ductal adenocarcinoma and to evaluate correlation with tumor grading. METHODS: Thirty-two patients with locally advanced pancreatic adenocarcinoma were included in this study. Lesions were evaluated by P-CT and biopsy after patient's informed consent. P-CT parameters have been assessed on a large single and on 6 small intratumoral ROIs. Values obtained have been compared and related to the tumor grading using Mann-Whitney U test. Sensibility, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy in predicting tumor grading have been calculated for cut-off values chosen by using ROC curves. RESULTS: Out of 32 lesions, 12 were classified as low grade and 20 as high grade. A statistically significant difference between high and low grade neoplasms were demonstrated for PEI and BV parameters. PEI and BV cut-off values were respectively 17.8 HU and 14.8 ml/100g. PEI identified high grade neoplasms with a 65% sensitivity, 92% specificity, 93% PPV, 61% NPV and 75% accuracy. BV identified high grade neoplasms with a 80% sensitivity, 75% specificity, 84% PPV, 69% NPV, 78% accuracy. Considering both PEI and BV, P-CT identified high grade lesions with a 60% sensitivity, 100% specificity, 100% PPV, 60% NPV and 75% accuracy. CONCLUSIONS: PEI and BV perfusion CT parameters proved their efficiency in identifying high grade pancreatic adenocarcinoma.

16 Article Impact of lymphadenectomy on survival after surgery for sporadic gastrinoma. 2012

Bartsch, D K / Waldmann, J / Fendrich, V / Boninsegna, L / Lopez, C L / Partelli, S / Falconi, M. ·Department of Surgery, University Hospital Giessen and Marburg, Marburg, Germany. ·Br J Surg · Pubmed #22864882.

ABSTRACT: BACKGROUND: The study was undertaken to determine prognostic factors and the value of systematic lymphadenectomy on survival in sporadic gastrinoma. METHODS: Patients with sporadic gastrinoma who underwent initial surgery during a 21-year period in two tertiary referral centres were analysed retrospectively with respect to clinical characteristics, operative procedures and outcome. RESULTS: Forty-eight patients with a median age of 52 (range 22-73) years were analysed. Some 18 patients had pancreatic and 26 had duodenal gastrinomas, whereas the primary tumour remained unidentified in four patients. After a median postoperative follow-up of 83 (range 3-296) months, 20 patients had no evidence of disease, 13 patients were alive with disease, 11 patients had died from the disease and four had died from unrelated causes. In 41 patients who underwent potentially curative surgery, systematic lymphadenectomy with excision of more than ten lymph nodes resulted in a higher rate of biochemical cure after surgery than no or selective lymphadenectomy (13 of 13 versus 18 of 28 patients; P = 0·017), with a trend towards prolonged disease specific survival (P = 0·062) and disease-free survival (P = 0·120), and a reduced risk of death (0 of 13 versus 7 of 24 patients; P = 0·037). Negative prognostic factors for disease specific survival were pancreatic location (P = 0·029), tumour size equal to or larger than 25 mm (P = 0·003), Ki-67 index more than 5 per cent (P < 0·001), preoperative gastrin level 3000 pg/ml or more (P = 0·003) and liver metastases (P < 0·001). Sex, age, type of surgery and presence of lymph node metastases had no influence on disease free or disease specific survival. CONCLUSION: In sporadic gastrinoma, systematic lymphadenectomy during initial surgery may reduce the risk of persistent disease and improve survival.

17 Article TNM staging of neoplasms of the endocrine pancreas: results from a large international cohort study. 2012

Rindi, G / Falconi, M / Klersy, C / Albarello, L / Boninsegna, L / Buchler, M W / Capella, C / Caplin, M / Couvelard, A / Doglioni, C / Delle Fave, G / Fischer, L / Fusai, G / de Herder, W W / Jann, H / Komminoth, P / de Krijger, R R / La Rosa, S / Luong, T V / Pape, U / Perren, A / Ruszniewski, P / Scarpa, A / Schmitt, A / Solcia, E / Wiedenmann, B. ·Institute of Anatomic Pathology, Università Cattolica del Sacro Cuore, Histopathology and Cytodiagnosis Unit, Policlinico Gemelli, Largo A. Gemelli, 8, Roma I-00168, Italy. guido.rindi@rm.unicatt.it ·J Natl Cancer Inst · Pubmed #22525418.

ABSTRACT: BACKGROUND: Both the European Neuroendocrine Tumor Society (ENETS) and the International Union for Cancer Control/American Joint Cancer Committee/World Health Organization (UICC/AJCC/WHO) have proposed TNM staging systems for pancreatic neuroendocrine neoplasms. This study aims to identify the most accurate and useful TNM system for pancreatic neuroendocrine neoplasms. METHODS: The study included 1072 patients who had undergone previous surgery for their cancer and for which at least 2 years of follow-up from 1990 to 2007 was available. Data on 28 variables were collected, and the performance of the two TNM staging systems was compared by Cox regression analysis and multivariable analyses. All statistical tests were two-sided. RESULTS: Differences in distribution of sex and age were observed for the ENETS TNM staging system. At Cox regression analysis, only the ENETS TNM staging system perfectly allocated patients into four statistically significantly different and equally populated risk groups (with stage I as the reference; stage II hazard ratio [HR] of death = 16.23, 95% confidence interval [CI] = 2.14 to 123, P = .007; stage III HR of death = 51.81, 95% CI = 7.11 to 377, P < .001; and stage IV HR of death = 160, 95% CI = 22.30 to 1143, P < .001). However, the UICC/AJCC/WHO 2010 TNM staging system compressed the disease into three differently populated classes, with most patients in stage I, and with the patients being equally distributed into stages II-III (statistically similar) and IV (with stage I as the reference; stage II HR of death = 9.57, 95% CI = 4.62 to 19.88, P < .001; stage III HR of death = 9.32, 95% CI = 3.69 to 23.53, P = .94; and stage IV HR of death = 30.84, 95% CI = 15.62 to 60.87, P < .001). Multivariable modeling indicated curative surgery, TNM staging, and grading were effective predictors of death, and grading was the second most effective independent predictor of survival in the absence of staging information. Though both TNM staging systems were independent predictors of survival, the UICC/AJCC/WHO 2010 TNM stages showed very large 95% confidence intervals for each stage, indicating an inaccurate predictive ability. CONCLUSION: Our data suggest the ENETS TNM staging system is superior to the UICC/AJCC/WHO 2010 TNM staging system and supports its use in clinical practice.

18 Article Pancreatic endocrine tumours: mutational and immunohistochemical survey of protein kinases reveals alterations in targetable kinases in cancer cell lines and rare primaries. 2012

Corbo, V / Beghelli, S / Bersani, S / Antonello, D / Talamini, G / Brunelli, M / Capelli, P / Falconi, M / Scarpa, A. ·ARC-NET Center for the Applied Research on Cancer-Networking, Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy. ·Ann Oncol · Pubmed #21447618.

ABSTRACT: BACKGROUND: Kinases represent potential therapeutic targets in pancreatic endocrine tumours (PETs). PATIENTS AND METHODS: Thirty-five kinase genes were sequenced in 36 primary PETs and three PET cell lines: (i) 4 receptor tyrosine kinases (RTK), epithelial growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), tyrosine-protein kinase KIT (KIT), platelet-derived growth factor receptor alpha (PDGFRalpha); (ii) 6 belonging to the Akt/mTOR pathway; and (iii) 25 frequently mutated in cancers. The immunohistochemical expression of the four RTKs and the copy number of EGFR and HER2 were assessed in 140 PETs. RESULTS: Somatic mutations were found in KIT in one and ATM in two primary neoplasms. Among 140 PETs, EGFR was immunopositive in 18 (13%), HER2 in 3 (2%), KIT in 16 (11%), and PDGFRalpha in 135 (96%). HER2 amplification was found in 2/130 (1.5%) PETs. KIT membrane immunostaining was significantly associated with tumour aggressiveness and shorter patient survival. PET cell lines QGP1, CM and BON harboured mutations in FGFR3, FLT1/VEGFR1 and PIK3CA, respectively. CONCLUSIONS: Only rare PET cases, harbouring either HER2 amplification or KIT mutation, might benefit from targeted drugs. KIT membrane expression deserves further attention as a prognostic marker. ATM mutation is involved in a proportion of PET. The finding of specific mutations in PET cell lines renders these models useful for preclinical studies involving pathway-specific therapies.

19 Article Hyperinsulinemic hypoglycemia associated with ectopic Cushing's syndrome due to a pancreatic endocrine tumor in a Type 2 diabetes mellitus patient: clinical implications of a rare association. 2011

Filippella, M / Davì, M V / Doveri, G / Lillaz, E / Ciccarelli, A / Massimetti, E / Toaiari, M / Falconi, M / Colao, A / Faggiano, A. ·SC Internal Medicine Unit of Diabetology and Endocrinology, Parini Hospital, Aosta, Italy. ·J Endocrinol Invest · Pubmed #20386090.

ABSTRACT: BACKGROUND: The coexistence of insulin and ACTH hypersecretion in the same patient is extremely rare. A diabetic patient with a pancreatic endocrine tumor (PET) co-secreting insulin and ACTH is even rarer and has never been described. The combination of these two endocrine syndromes results in a peculiar clinical picture. AIM: To determine the cause of glycemic variations in a patient with previously stable diabetes mellitus. SUBJECTS AND METHODS: This is a clinical case report from the Endocrinology Unit of Aosta Hospital and Internal Medicine and Surgical Unit of Verona University. A 69-yr-old diabetic patient was hospitalized for recurrent severe hypoglycemic events persistent after withdrawal of anti-diabetic drugs. The causes of hypoglycemia and subsequent resumption of hyperglycemia were investigated. RESULTS: An insulin-secreting PET was diagnosed. Diazoxide and octreotide therapy initially was able to control hypoglycemic symptoms, then, a Cushing's syndrome occurred resulting in worsening of diabetes control. ACTH was found to be released by the PET previously diagnosed as an insulin-secreting tumor. The tumor was removed and the histology was consistent with a well differentiated endocrine carcinoma. After surgery, adrenal function was normal and insulin therapy was again necessary to control diabetes. CONCLUSIONS: A single PET may be responsible for both a hyperinsulinemic and a Cushing's syndrome. When this rare association occurs, each of the two syndromes may affect the other resulting in a peculiar clinical course. Finally, an insulin-secreting PET has to be kept in mind as a rare cause of hypoglycemia in diabetic patients.

20 Minor Implications of the new histological classification (WHO 2010) for pancreatic neuroendocrine neoplasms. 2012

Crippa, S / Partelli, S / Boninsegna, L / Falconi, M. · ·Ann Oncol · Pubmed #22753260.

ABSTRACT: -- No abstract --