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Pancreatic Neoplasms: HELP
Articles by Vincenzo Mazzaferro
Based on 14 articles published since 2010
(Why 14 articles?)

Between 2010 and 2020, Vincenzo Mazzaferro wrote the following 14 articles about Pancreatic Neoplasms.
+ Citations + Abstracts
1 Review Entering the third decade of experience with octreotide LAR in neuroendocrine tumors: A review of current knowledge. 2019

Pusceddu, Sara / Prinzi, Natalie / Raimondi, Alessandra / Corti, Francesca / Buzzoni, Roberto / Di Bartolomeo, Maria / Seregni, Ettore / Maccauro, Marco / Coppa, Jorgelina / Milione, Massimo / Mazzaferro, Vincenzo / de Braud, Filippo. ·1 Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, ENETS Center of Excellence, Milan, Italy. · 2 Department of Nuclear Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, ENETS Center of Excellence, Milan, Italy. · 3 Department of Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, ENETS Center of Excellence, Milan, Italy. · 4 Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, ENETS Center of Excellence, Milan, Italy. · 5 University of Milan, Milan, Italy. ·Tumori · Pubmed #29714658.

ABSTRACT: Gastroenteropancreatic neuroendocrine tumors (NETs) are a relatively rare group of heterogeneous neoplasms. The most significant advance in therapy of NETs has been the advent of the somatostatin analog octreotide, which represents a cornerstone in their management and dramatically changed the therapeutic landscape. Octreotide long-acting release (LAR) was developed to overcome some of the limitations of octreotide. Several clinical studies, including PROMID and RADIANT-2, have validated the clinical benefits of octreotide LAR in NETs, with tumor shrinkage in about 10% of patients and tumor stabilization in roughly half of cases. While the use of octreotide LAR is well-consolidated in NETs, some open questions remain. These include the use of high-dose octreotide LAR, as there is evidence that higher dose may provide longer disease control, and nonstandard treatment schedules, with administration every 21 days instead of 28 days, as well as their use in combination with targeted agents or peptide receptor radiotherapy in clinical practice. After 3 decades of clinical experience with octreotide LAR, the drug has a well-established safety profile. It is well-tolerated and treatment discontinuations due to adverse events are uncommon. One exception is cholelithiasis, which may increase with longer duration of treatment. According to the literature data, octreotide LAR is currently recommended in both functioning and nonfunctioning advanced NETs. This review summarizes the available clinical data with octreotide LAR and also provides future perspectives on its possible uses in patients with NETs.

2 Review Metformin with everolimus and octreotide in pancreatic neuroendocrine tumor patients with diabetes. 2016

Pusceddu, Sara / Buzzoni, Roberto / Vernieri, Claudio / Concas, Laura / Marceglia, Sara / Giacomelli, Luca / Milione, Massimo / Leuzzi, Livia / Femia, Daniela / Formisano, Barbara / Mazzaferro, Vincenzo / de Braud, Filippo. ·Medical Oncology Unit 1, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. · Day Hospital/Outpatient Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. · IFOM, FIRC Institute of Molecular Oncology, 20139 Milan, Italy. · Department of Information & Bioengineering, Politecnico University, Milan, Italy. · Department of Surgical Sciences & Integrated Diagnostics, School of Medicine, Genova University, Genoa, Italy. · Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. · Gastro-Intestinal Surgery, Liver Transplantation & Hepatology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. ·Future Oncol · Pubmed #26890290.

ABSTRACT: A bidirectional relationship seems to exist between diabetes mellitus and development of pancreatic tumors. Metformin, the most widely used drug in the treatment of Type 2 diabetes mellitus, has recently emerged as a potentially active agent in cancer chemoprevention and treatment. In this article, we discuss the potential correlation between glycemic status, administration of antiglycemic treatments, such as metformin or insulin, and prognosis of pancreatic neuroendocrine tumors patients treated with everolimus and octreotide, on the basis of existing evidence and our experience.

3 Review Evolution in the treatment of gastroenteropancreatic-neuroendocrine neoplasms, focus on systemic therapeutic options: a systematic review. 2015

Pusceddu, Sara / De Braud, Filippo / Festinese, Fabrizio / Bregant, Cristina / Lorenzoni, Alice / Maccauro, Marco / Milione, Massimo / Concas, Laura / Formisano, Barbara / Leuzzi, Livia / Mazzaferro, Vincenzo / Buzzoni, Roberto. ·Department of Medical Oncology, ENETS Center of Excellence, Fondazione IRCCS 'Istituto Nazionale dei Tumori', Milan, Italy. · Department of Pharmacy, ENETS Center of Excellence, Fondazione IRCCS 'Istituto Nazionale dei Tumori', Milan, Italy. · Department of Nuclear Medicine, ENETS Center of Excellence, Fondazione IRCCS 'Istituto Nazionale dei Tumori', Milan, Italy. · Department of Pathology, ENETS Center of Excellence, Fondazione IRCCS 'Istituto Nazionale dei Tumori', Milan, Italy. · Department of Surgery & liver transplantation, ENETS Center of Excellence, Fondazione IRCCS 'Istituto Nazionale dei Tumori', Milan, Italy. ·Future Oncol · Pubmed #26161929.

ABSTRACT: Neuroendocrine neoplasms (NENs) are a group of heterogeneous tumors. The present review discusses current therapeutic strategies for the treatment of gastro-entero-pancreatic NEN. Several systemic options are currently available, including medical systemic chemotherapy, biological drugs, somatostatin analogs and peptide receptor radionuclide therapy. The carcinoid syndrome can be adequately controlled with somatostatin analogs; chemotherapy has shown positive outcomes in poor prognosis patients, and peptide receptor radionuclide therapy is a promising treatment based on the use of radioisotopes for advanced disease expressing somatostatin receptors. Targeted therapies, such as multikinase inhibitors and monoclonal antibodies are also recommended or under evaluation for the treatment of advanced NENs, but some critical issues in clinical practice remain unresolved. Depending upon the development of the disease, a multimodal approach is recommended. The treatment strategy for metastatic patients should be planned by a multidisciplinary team in order to define the optimal sequence of treatments.

4 Clinical Trial Permanent Pancreatic Duct Occlusion With Neoprene-based Glue Injection After Pancreatoduodenectomy at High Risk of Pancreatic Fistula: A Prospective Clinical Study. 2019

Mazzaferro, Vincenzo / Virdis, Matteo / Sposito, Carlo / Cotsoglou, Christian / Droz Dit Busset, Michele / Bongini, Marco / Flores, Maria / Prinzi, Natalie / Coppa, Jorgelina. ·Department of Oncology, University of Milan, Milan, Italy. · Hepato-Pancreatic-Biliary Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. · Clinical Oncology and Endocrinology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. ·Ann Surg · Pubmed #31567180.

ABSTRACT: OBJECTIVE: The aim of this study was to assess safety and efficacy of pancreatic duct occlusion (PDO) with neoprene-based glue in selected patients undergoing pancreatoduodenectomy (PD) at high risk of postoperative pancreatic fistula (POPF). BACKGROUND DATA: PD is the reference standard approach for tumors of the pancreaticoduodenal region. POPF is the most relevant complication after PD. PDO has been proposed as an alternative to anastomosis to manage the pancreatic stump. METHODS: A single-center, prospective, nonrandomized trial enrolled 100 consecutive PD for cancer. Patients at high risk for POPF according to Fistula Risk Score (FRS) >15% (≥6 points) were treated with PDO using neoprene glue (study cohort); patients with FRS ≤15% (≤5 points) received pancreaticojejunal anastomosis (PJA: control cohort). Primary endpoint was complication rate grade ≥3 according to Dindo-Clavien Classification (DCC). Other postoperative outcomes were monitored (ClinicalTrials.gov NCT03738787). RESULTS: Fifty-one patients underwent PDO and 49 PJA. DCC ≥3, postoperative mortality, and POPF grade B-C were 25.5% versus 24.5% (P = 0.91), 5.9% versus 2% (P = 0.62), and 11.8% versus 16.3% (P = 0.51) in the study versus control cohort, respectively. At 1 and 3 years, new-onset diabetes was diagnosed in 13.7% and 36.7% of the study cohort versu 4.2% and 12.2% in controls (P = 0.007). CONCLUSIONS: PDO with neoprene-based glue is a safe technique that equalizes early outcome of selected patients at high risk of POPF to those at low risk undergoing PJA. Neoprene-based PDO, however, triples the risk of diabetes at 1 and 3 years.

5 Article Somatostatin analogs in association with peptide receptor radionucleotide therapy in advanced well-differentiated NETs. 2019

Prinzi, Natalie / Raimondi, Alessandra / Maccauro, Marco / Milione, Massimo / Garanzini, Enrico / Torchio, Martina / Corti, Francesca / Nichetti, Federico / Russo, Giuseppe Lo / Giacomelli, Luca / Mazzaferro, Vincenzo / Bartolomeo, Maria Di / Seregni, Ettore / Braud, Filippo de / Pusceddu, Sara. ·Fondazione IRCCS Istituto Nazionale Tumori Milano, ENETS Center of Excellence, Department of Medical Oncology, Milan, Italy. · Postgraduation School in Radiodiagnostics, Università degli Studi di Milano, Milan, Italy. ·Future Oncol · Pubmed #31424273.


6 Article The Italian Rare Pancreatic Exocrine Cancer Initiative. 2019

Brunetti, Oronzo / Luchini, Claudio / Argentiero, Antonella / Tommasi, Stefania / Mangia, Anita / Aprile, Giuseppe / Marchetti, Paolo / Vasile, Enrico / Casadei Gardini, Andrea / Scartozzi, Mario / Barni, Sandro / Delfanti, Sara / De Vita, Fernando / Di Costanzo, Francesco / Milella, Michele / Cella, Chiara Alessandra / Berardi, Rossana / Cataldo, Ivana / Santini, Daniele / Doglioni, Claudio / Maiello, Evaristo / Lawlor, Rita T / Mazzaferro, Vincenzo / Lonardi, Sara / Giuliante, Felice / Brandi, Giovanni / Scarpa, Aldo / Cascinu, Stefano / Silvestris, Nicola. ·1 Medical Oncology Unit, IRCCS Cancer Institute "Giovanni Paolo II" of Bari, Bari, Italy. · 2 Department of Diagnostics and Public Health, Section of Pathology, University of Verona, Verona, Italy. · 3 Molecular Diagnostics and Pharmacogenetics Unit, IRCCS Istituto Tumori "Giovanni Paolo II", Bari, Italy. · 4 Functional Biomorphology Laboratory, IRCCS-Istituto Tumori, Bari, Italy. · 5 Medical Oncology Unit, Hospital of Vicenza, Vicenza, Italy. · 6 Medical Oncology Unit, Sant'Andrea Hospital, University of Rome La Sapienza, Rome, Italy. · 7 Medical Oncology Unit, University Hospital of Pisa, Pisa, Italy. · 8 Medical Oncology Unit, Scientific Institute of Romagna for the Study and Treatment of Cancer (IRST), Meldola, Italy. · 9 Medical Oncology Unit, University of Cagliari, Cagliari, Italy. · 10 Medical Oncology Unit, ASST Bergamo Ovest, Treviglio, Italy. · 11 Medical Oncology Unit, IRCCS Foundation Polyclinic San Matteo, Pavia, Italy. · 12 Medical Oncology Unit, II University of Naples, Naples, Italy. · 13 Medical Oncology Unit, Careggi University Hospital, Florence, Italy. · 14 Medical Oncology Unit, "Regina Elena" National Cancer Institute, Rome, Italy. · 15 Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology (IEO), Milan, Italy. · 16 Medical Oncology Unit, Polytechnic University of the Marche, "Ospedali Riuniti Ancona," Ancona, Italy. · 17 Department of Pathology and Diagnostics, University of Verona Hospital Trust, Policlinico GB Rossi, Verona, Italy. · 18 Medical Oncology Unit, University Campus Biomedico, Rome, Italy. · 19 Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy. · 20 Medical Oncology Unit, IRCCS "Casa Sollievo della Sofferenza" Foundation, San Giovanni Rotondo, Italy. · 21 Arc-Net Centre for Applied Research on Cancer, University and Hospital Trust of Verona, Verona, Italy. · 22 Hepato-Biliary-Pancreatic Surgery, University of Milan, Istituto Nazionale Tumori, Fondazione IRCCS, Milan, Italy. · 23 Medical Oncology Unit, IRCCS Veneto Institute of Oncology (IOV), Padua, Italy. · 24 Hepatobiliary Surgery Unit, IRCCS A. Gemelli Polyclinic Foundation, Catholic University of the Sacred Heart, Rome, Italy. · 25 Oncology Unit, Department of Experimental, Diagnostic and Specialty Medicine, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy. · 26 Medical Oncology Unit, Modena Cancer Center, University Hospital of Modena, Modena, Italy. · 27 Scientific Direction, IRCCS Cancer Institute "Giovanni Paolo II" of Bari, Bari, Italy. ·Tumori · Pubmed #30967031.

ABSTRACT: INTRODUCTION: Exocrine pancreatic cancers include common type pancreatic ductal adenocarcinoma and cystic neoplasms, which account for 85% and 10% of cases, respectively. The remaining 5% are rare histotypes, comprising adenosquamous carcinoma, acinar cell carcinoma, signet ring cell carcinoma, medullary carcinoma, pancreatoblastoma, hepatoid carcinoma, undifferentiated carcinoma and its variant with osteoclast-like giant cells, solid pseudopapillary carcinoma, and carcinosarcoma. Due to their low incidence, little knowledge is available on their clinical and molecular features as well as on treatment choices. The national initiative presented here aims at the molecular characterization of series of rare histotypes for which therapeutic and follow-up data are available. METHODS: A nationwide Italian Rare Pancreatic Cancer (IRaPaCa) task force whose first initiative is a multicentric retrospective study involving 21 Italian cancer centers to retrieve histologic material and clinical and treatment data of at least 100 patients with rare exocrine pancreatic cancers has been created. After histologic revision by a panel of expert pathologists, DNA and RNA from paraffin tissues will be investigated by next-generation sequencing using molecular pathway-oriented and immune-oriented mutational and expression profiling panels constructed availing of the information from the International Cancer Genome Consortium. Bioinformatic analysis of data will drive validation studies by immunohistochemistry and in situ hybridization, as well as nanostring assays. CONCLUSIONS: We expect to gather novel data on rare pancreatic cancer types that will be useful to inform the design of therapeutic choices.

7 Article Impact of systemic and tumor lipid metabolism on everolimus efficacy in advanced pancreatic neuroendocrine tumors (pNETs). 2019

Vernieri, Claudio / Pusceddu, Sara / Fucà, Giovanni / Indelicato, Pietro / Centonze, Giovanni / Castagnoli, Lorenzo / Ferrari, Elisa / Ajazi, Arta / Pupa, Serenella / Casola, Stefano / Foiani, Marco / Mazzaferro, Vincenzo / Pruneri, Giancarlo / Milione, Massimo / de Braud, Filippo. ·Medical Oncology Department, Fondazione IRCCS Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy. · IFOM, the FIRC Institute of Molecular Oncology, Milan, Italy. · Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy. · Molecular Targeting Unit, Department of Research, Fondazione IRCCS Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy. · Oncology and Haemato-Oncology Department, University of Milan, Milan, Italy. · Hepato-Bilio-Pancreatic Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy. · School of Medicine, University of Milan, Milan, Italy. ·Int J Cancer · Pubmed #30520016.

ABSTRACT: The mTOR inhibitor everolimus is effective against advanced pancreatic neuroendocrine tumors (pNETs). However, it can cause metabolic adverse events, such as hyperglycemia, hypertriglyceridemia and hypercholesterolemia. In this work we aimed at evaluating the impact of systemic and tumor lipid metabolism on everolimus efficacy. We carried out a monocentric, retrospective study to correlate plasma triglyceride and cholesterol levels with the progression free survival (PFS) of advanced pNET patients treated with everolimus. In formalin fixed, paraffin embedded (FFPE) tumor specimens, we also assessed by mRNA quantification and immunohistochemistry the expression of acetyl-CoA carboxylase 1 (ACC1) and fatty acid synthase (FASN), two enzymes crucially involved in fatty acid biosynthesis, and we analyzed their impact on PFS. We evaluated 58 consecutive pNET patients who started everolimus between December 2006 and January 2015. Patients with higher plasma triglycerides during the first 3 months of treatment had an increased risk of disease progression (aHR 3.08, 95% CIs 1.15-8.21; p = 0.025). In 23 FFPE tumor specimens amenable for IHC evaluations, we found a positive correlation between ACC1 and FASN at both mRNA (r = 0.87, p = 0.00045) and protein (r = 0.68, p = 0.0004) level. Patients with higher ACC1 protein expression in metastatic lesions had significantly lower PFS when compared to patients with lower ACC1 levels (5.5 vs. 36 months; aHR 4.49, 95% CIs 1.08-18.72; p = 0.039). In conclusion, systemic and tumor lipid metabolism are associated with the PFS of everolimus-treated patients with advanced pNETs; based on these findings, dietary and pharmacological interventions targeting lipid metabolism could improve everolimus efficacy in this patient population.

8 Article Ki-67 and presence of liver metastases identify different progression-risk classes in pancreatic neuroendocrine neoplasms (pNEN) undergoing resection. 2019

Milione, Massimo / Maisonneuve, Patrick / Pellegrinelli, Alessio / Spaggiari, Paola / Centonze, Giovanni / Coppa, Jorgelina / Delconte, Gabriele / Droz Dit Busset, Michele / Lanhazo, Oleksandra / Pruneri, Giancarlo / Mazzaferro, Vincenzo. ·Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy. · Division of Epidemiology and Biostatistics, IEO, European Institute of Oncology IRCCS, Milan, Italy. · Department of Pathology, Cancer Center Humanitas Research Hospital, Rozzano Milan, Italy. · Surgery and Neuroendocrine Tumor Group, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy. · Endoscopy, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy. · Surgery and Neuroendocrine Tumor Group, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy. Electronic address: michele.drozditbusset@istitutotumori.mi.it. · Department of Surgery, Transcarpathian Regional Hospital, Užhorod, Ukraine. · Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy; University of Milan, School of Medicine, Italy. · Surgery and Neuroendocrine Tumor Group, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy; University of Milan, School of Medicine, Italy. ·Eur J Surg Oncol · Pubmed #30366875.

ABSTRACT: In pancreatic neuroendocrine neoplasms (pNEN), size ≤2 cm and Ki-67 < 3% suggest indolent behavior, but no factor alone predicts prognosis. We investigated factors predictive of tumor progression in 80 pNENs surgically resected in a single Institution from 1995 to 2015. At multivariable analysis the only two independent variables related to PFS were Ki-67 (HR 2.97; 95%CI 1.26-7.02) and presence of synchronous liver metastases (HR 3.60; 95%CI 1.70-7.61). Using Ki-67 < 3% and M0 as reference, the HR for tumor progression was 3.21 (95%CI 1.18-8.74) for M0 patients with Ki-67 3-20%, 5.06 (2.29-11.2) for M1 patients with Ki-67 ≤ 20% and 24.3 (6.64-89.2) for those with Ki-67 > 20%. Tumor size (≤2 vs. >2 cm) was not a predictive factor at any analysis. Intra-class correlation of Ki-67 values on pre-surgical biopsies vs. surgical specimens was 0.99 and Ki-67 classes were correctly identified in 97% of biopsies. Ki-67 and presence of liver metastases are the major prognostic factors in pNEN and identify different progression risks regardless of tumor size. Pre-surgical pNEN biopsy for Ki-67 assessment should be included in the evaluation of patients with 1-2 cm tumors to help in the decision on whether to perform surgical resection.

9 Article Resection of pancreatic cancer in Europe and USA: an international large-scale study highlighting large variations. 2019

Huang, Lei / Jansen, Lina / Balavarca, Yesilda / Molina-Montes, Esther / Babaei, Masoud / van der Geest, Lydia / Lemmens, Valery / Van Eycken, Liesbet / De Schutter, Harlinde / Johannesen, Tom B / Fristrup, Claus W / Mortensen, Michael B / Primic-Žakelj, Maja / Zadnik, Vesna / Becker, Nikolaus / Hackert, Thilo / Mägi, Margit / Cassetti, Tiziana / Sassatelli, Romano / Grützmann, Robert / Merkel, Susanne / Gonçalves, Ana F / Bento, Maria J / Hegyi, Péter / Lakatos, Gábor / Szentesi, Andrea / Moreau, Michel / van de Velde, Tony / Broeks, Annegien / Sant, Milena / Minicozzi, Pamela / Mazzaferro, Vincenzo / Real, Francisco X / Carrato, Alfredo / Molero, Xavier / Besselink, Marc G / Malats, Núria / Büchler, Markus W / Schrotz-King, Petra / Brenner, Hermann. ·Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. · German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. · Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany. · Geneticand Molecular Epidemiology Group, Spanish National Cancer Research Centre (CNIO), CIBERONC, ISCIII, Madrid, Spain. · Netherlands Cancer Registry (NCR), Netherlands Comprehensive Cancer Organization (IKNL), Utrecht, Netherlands. · Belgian Cancer Registry (BCR), Brussels, Belgium. · Registry Department, The Cancer Registry of Norway (CRN), Oslo, Norway. · Danish Pancreatic Cancer Database (DPCD), Odense, Denmark. · Danish Pancreatic Cancer Group, HPB Section, Department of Surgery, Odense University Hospital, Odense, Denmark. · Epidemiology and Cancer Registry, Institute of Oncology Ljubljana, Ljubljana, Slovenia. · Clinical Cancer Registry, DKFZ and NCT, Heidelberg, Germany. · Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany. · Estonian Cancer Registry, National Institute for Health Development, Tallinn, Estonia. · Pancreatic Cancer Registry of Reggio Emilia Province, Unit of Gastroenterology and Digestive Endoscopy AUSL-RE, Local Health Authority-IRCCS, Reggio Emilia, Italy. · Department of Surgery, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany. · Departments of Epidemiology, Portuguese Oncology Institute of Porto (IPOP), Porto, Portugal. · Institute for Translational Medicine, University of Pécs, Pécs, Hungary. · Department of Oncology, St. Istvan and St. Laszlo Hospital and Out-Patient Department, Budapest, Hungary. · Department of Surgical Oncology, Jules Bordet Institute (IJB), Brussels, Belgium. · Biometrics Department, The Netherlands Cancer Institute (NKI), Amsterdam, Netherlands. · Analytical Epidemiology and Health Impact Unit, Department of Preventive and Predictive Medicine, Fondazione IRCCS, Istituto Nazionale dei Tumori (INT), Milan, Italy. · Hepato-Biliary Surgery Unit, Istituto Nazionale dei Tumori (INT), and University of Milan, Milan, Italy. · Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), CIBERONC, Madrid, Spain. · Department de Ciencies Experimentals i de la, Universitat Pompeu Fabra, Barcelona, Spain. · Department of Oncology, Ramon y Cajal University Hospital, IRYCIS, Alcala University, CIBERONC, Madrid, Spain. · Hospital Universitari Vall d'Hebron, Exocrine Pancreas Research Unit and Vall d'Hebron Research Institute (VHIR), Universitat Autonoma de Barcelona, Campus de la UAB, Barcelona, Spain. · CIBEREHD and CIBERESP, Madrid, Spain. · Dutch Pancreatic Cancer Group, Academic Medical Centre Amsterdam, Amsterdam, Netherlands. ·Gut · Pubmed #29158237.

ABSTRACT: OBJECTIVE: Resection can potentially cure resectable pancreatic cancer (PaC) and significantly prolong survival in some patients. This large-scale international study aimed to investigate variations in resection for PaC in Europe and USA and determinants for its utilisation. DESIGN: Data from six European population-based cancer registries and the US Surveillance, Epidemiology, and End Results Program database during 2003-2016 were analysed. Age-standardised resection rates for overall and stage I-II PaCs were computed. Associations between resection and demographic and clinical parameters were assessed using multivariable logistic regression models. RESULTS: A total of 153 698 records were analysed. In population-based registries in 2012-2014, resection rates ranged from 13.2% (Estonia) to 21.2% (Slovenia) overall and from 34.8% (Norway) to 68.7% (Denmark) for stage I-II tumours, with great international variations. During 2003-2014, resection rates only increased in USA, the Netherlands and Denmark. Resection was significantly less frequently performed with more advanced tumour stage (ORs for stage III and IV versus stage I-II tumours: 0.05-0.18 and 0.01-0.06 across countries) and increasing age (ORs for patients 70-79 and ≥80 versus those <60 years: 0.37-0.63 and 0.03-0.16 across countries). Patients with advanced-stage tumours (stage III-IV: 63.8%-81.2%) and at older ages (≥70 years: 52.6%-59.5%) receiving less frequently resection comprised the majority of diagnosed cases. Patient performance status, tumour location and size were also associated with resection application. CONCLUSION: Rates of PaC resection remain low in Europe and USA with great international variations. Further studies are warranted to explore reasons for these variations.

10 Article Metformin Use Is Associated With Longer Progression-Free Survival of Patients With Diabetes and Pancreatic Neuroendocrine Tumors Receiving Everolimus and/or Somatostatin Analogues. 2018

Pusceddu, Sara / Vernieri, Claudio / Di Maio, Massimo / Marconcini, Riccardo / Spada, Francesca / Massironi, Sara / Ibrahim, Toni / Brizzi, Maria Pia / Campana, Davide / Faggiano, Antongiulio / Giuffrida, Dario / Rinzivillo, Maria / Cingarlini, Sara / Aroldi, Francesca / Antonuzzo, Lorenzo / Berardi, Rossana / Catena, Laura / De Divitiis, Chiara / Ermacora, Paola / Perfetti, Vittorio / Fontana, Annalisa / Razzore, Paola / Carnaghi, Carlo / Davì, Maria Vittoria / Cauchi, Carolina / Duro, Marilina / Ricci, Sergio / Fazio, Nicola / Cavalcoli, Federica / Bongiovanni, Alberto / La Salvia, Anna / Brighi, Nicole / Colao, Annamaria / Puliafito, Ivana / Panzuto, Francesco / Ortolani, Silvia / Zaniboni, Alberto / Di Costanzo, Francesco / Torniai, Mariangela / Bajetta, Emilio / Tafuto, Salvatore / Garattini, Silvio Ken / Femia, Daniela / Prinzi, Natalie / Concas, Laura / Lo Russo, Giuseppe / Milione, Massimo / Giacomelli, Luca / Buzzoni, Roberto / Delle Fave, Gianfranco / Mazzaferro, Vincenzo / de Braud, Filippo. ·Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, ENETS Center of Excellence, Milan, Italy. Electronic address: sara.pusceddu@istitutotumori.mi.it. · Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, ENETS Center of Excellence, Milan, Italy; Fondazione Istituto FIRC di Oncologia Molecolare (IFOM), Milan, Italy. · Dipartimento di Oncologia, Università degli Studi di Torino, A. O. Ordine Mauriziano, Turin, Italy. · Dipartimento di Oncologia, Santa Chiara Hospital, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy. · IEO - Istituto Europeo di Oncologia, ENETS Center of Excellence, Milan, Italy. · Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy. · Centro di Osteoncologia e Tumori Rari, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. · Azienda Ospedaliera Universitaria San Luigi Gonzaga, Orbassano, Italy. · Policlinico Sant'Orsola Malpighi, Bologna, Italy. · Unità di chirurgia tiroidea e paratiroidea, Istituto Nazionale per lo studio e la cura dei tumori "Fondazione G. Pascale" - IRCCS, Naples, Italy. · IOM- Istituto Oncologico del Mediterraneo, Catania, Italy. · Azienda Ospedaliera Universitaria Sant'Andrea, ENETS Center of Excellence, Rome, Italy. · Azienda Ospedaliera Universitaria, Verona, Italy. · Fondazione Poliambulanza, Brescia, Italy. · A. O. U. Careggi, Firenze, Italy. · Azienda Ospedaliero Universitaria Ospedali Riuniti, Ancona, Italy. · Policlinico di Monza, Monza, Italy. · IRCCS Fondazione Pascale, ENETS Center of Excellence, Naples, Italy. · Azienda Ospedaliero Universitaria Santa Maria della Misericordia, Udine, Italy. · Fondazione IRCCS Policlinico San Matteo, SC oncologia, Pavia, Italy. · Policlinico di Modena, Italy. · Unit of Endocrinology, Ospedale Mauriziano, Torino, Italy. · Istituto Clinico Humanitas, Rozzano, ENETS Center of Excellence, Italy. · Ospedale Policlinico Borgo Roma, Verona, Italy. · Ospedale S Croce e Carle, Cuneo, Italy. · Ospedale Valduce Como, Italy. · Endocrinology Section, Department of Clinical Medicine and Surgery, "Federico II" University of Naples, Italy. · Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, ENETS Center of Excellence, Milan, Italy. · Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, ENETS Center of Excellence, Milan, Italy; Medical-Surgical Science and Traslational Medicine Departement, Sapienza University, Rome, Italy. · Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Italy. · Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, ENETS Center of Excellence, Milan, Italy; Universita' degli Studi di Milano, Milan, Italy. ·Gastroenterology · Pubmed #29655834.

ABSTRACT: BACKGROUND & AIMS: Metformin seems to have anticancer effects. However, it is not clear whether use of glycemia and metformin affect outcomes of patients with advanced pancreatic neuroendocrine tumors (pNETs). We investigated the association between glycemia and progression-free survival (PFS) of patients with pNETs treated with everolimus and/or somatostatin analogues, as well as the association between metformin use and PFS time. METHODS: We performed a retrospective analysis of 445 patients with advanced pNET treated at 24 medical centers in Italy from 1999 through 2015. Data on levels of glycemia were collected at time of diagnosis of pNET, before treatment initiation, and during treatment with everolimus (with or without somatostatin analogues), octreotide, or lanreotide. Diabetes was defined as prior or current use of glycemia control medication and/or fasting plasma glucose level ≥ 126 mg/dL, hemoglobin A1c ≥ 6.5% (48 mmol/L), or a random sample of plasma glucose ≥ 200 mg/dL (11.1 mmol/L), with reported classic symptoms of hyperglycemia or hyperglycemic crisis. Patients were assigned to groups based on diagnosis of diabetes before or during antitumor therapy. PFS was compared between patients with vs without diabetes. Among patients with diabetes, the association between metformin use and PFS was assessed. We performed sensitivity and landmark analyses to exclude patients who developed diabetes while receiving cancer treatment and to exclude a potential immortal time bias related to metformin intake. RESULTS: PFS was significantly longer in patients with diabetes (median, 32.0 months) than without diabetes (median, 15.1 months) (hazard ratio for patients with vs without diabetes, 0.63; 95% confidence interval, 0.50-0.80; P = .0002). PFS of patients treated with metformin was significantly longer (median PFS, 44.2 months) than for patients without diabetes (hazard ratio for survival of patients with diabetes receiving metformin vs without diabetes, 0.45; 95% confidence interval, 0.32-0.62; P < .00001) and longer than for patients with diabetes receiving other treatments (median PFS, 20.8 months; hazard ratio, 0.49; 95% confidence interval, 0.34-0.69; P < .0001). In multivariable analysis, adjusted for other factors associated with outcomes, metformin was associated with longer PFS but level of glycemia was not. Metformin was associated with increased PFS of patients receiving somatostatin analogues and in those receiving everolimus, with or without somatostatin analogues. Sensitivity and landmark analyses produced similar results. CONCLUSIONS: In a retrospective study of patients with pNETs, we found a significant association between metformin use and longer PFS.

11 Article The role of wireless capsule endoscopy (WCE) in the detection of occult primary neuroendocrine tumors. 2017

Furnari, Manuele / Buda, Andrea / Delconte, Gabriele / Citterio, Davide / Voiosu, Theodor / Ballardini, Giovanni / Cavallaro, Flaminia / Savarino, Edoardo / Mazzaferro, Vincenzo / Meroni, Emanuele. ·Department of Internal Medicine, Gastroenterology Unit, IRCCS, University of Genoa, Italy. manuelefurnari@gmail.com. · Gastroenterology Unit, Santa Maria Del Parato Hospital, Feltre, Italy. · Department of Surgery, Endoscopy and Gastrointestinal Surgery Units, Fondazione IRCCS Istituto Nazionale dei Tumori,Milan, Italy. · Department of Surgery, Endoscopy and Gastrointestinal Surgery Units, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. · Gastroenterology Department, Colentina Clinical Hospital, Bucharest, Romania. · Department of Surgery, Oncology and Gastroenterology, Gastroenterology Unit, University of Padua, Italy. · Regional Hospital Beata Vergine, EOC, Mendrisio, Switzerland. ·J Gastrointestin Liver Dis · Pubmed #28617885.

ABSTRACT: BACKGROUND AND AIMS: Neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms with unclear etiology that may show functioning or non-functioning features. Primary tumor localization often requires integrated imaging. The European Neuroendocrine Tumors Society (ENETS) guidelines proposed wireless-capsule endoscopy (WCE) as a possible diagnostic tool for NETs, if intestinal origin is suspected. However, its impact on therapeutic management is debated. We aimed to evaluate the yield of WCE in detecting intestinal primary tumors in patients showing liver NET metastases when first-line investigations are inconclusive. METHOD: Twenty-four patients with a histological diagnosis of metastatic NET from liver biopsy and no evidence of primary lesions at first-line investigations were prospectively studied in an ENETS-certified tertiary care center. Wireless-capsule endoscopy was requested before explorative laparotomy and intra-operative ultrasound. The diagnostic yield of WCE was compared to the surgical exploration. RESULTS: Sixteen subjects underwent surgery; 11/16 had positive WCE identifying 16 bulging lesions. Mini-laparotomy found 13 NETs in 11/16 patients (9 small bowel, 3 pancreas, 1 bile ducts). Agreement between WCE and laparotomy was recorded in 9 patients (Sensitivity=75%; Specificity=37.5%; PPV=55%; NPV=60%). Correspondence assessed per-lesions produced similar results (Sensitivity=70%; Specificity=25%; PPV=44%; NPV=50%). No capsule retentions were recorded. CONCLUSIONS: Wireless-capsule endoscopy is not indicated as second-line investigation for patients with gastro-entero-pancreatic NETs. In the setting of a referral center, it might provide additional information when conventional investigations are inconclusive about the primary site.

12 Article Clinical Impact of Pancreatic Metastases from Renal Cell Carcinoma: A Multicenter Retrospective Analysis. 2016

Grassi, Paolo / Doucet, Ludovic / Giglione, Palma / Grünwald, Viktor / Melichar, Bohuslav / Galli, Luca / De Giorgi, Ugo / Sabbatini, Roberto / Ortega, Cinzia / Santoni, Matteo / Bamias, Aristotelis / Verzoni, Elena / Derosa, Lisa / Studentova, Hana / Pacifici, Monica / Coppa, Jorgelina / Mazzaferro, Vincenzo / de Braud, Filippo / Porta, Camillo / Escudier, Bernard / Procopio, Giuseppe. ·Medical Oncology 1, Fondazione IRCCS Istituto Nazionale Tumori, via G. Venezian 1, 20133, Milano, Italy. · Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France. · Medical Oncology, IRCCS San Matteo University Hospital Foundation, Viale Camillo Golgi, 19, 27100, Pavia, Italy. · Clinic for Haematology, Hemostasis, Oncology and Stemcelltransplantation, Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany. · Dept of Oncology, Palacký University Medical School and Teaching Hospital, I.P. Pavlova 6, 775 20, Olomouc, Czech Republic. · Medical Oncology 2, A.O.U.P., Istituto Toscano Tumori, via Roma 67, 56126, Pisa, Italy. · Dept of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, via P. Maroncelli 40, 47014, Meldola, Italy. · Dept of Oncology and Haematology and Respiratory Disease, University Hospital, Via del Pozzo 71, 41124, Modena, Italy. · Medical Oncology 1 - Candiolo Cancer Institute-FPO, IRCCS, Strada Provinciale, 142 km 3,95, 10060, Candiolo, Italy. · Medical Oncology, AOU Ospedali Riuniti, Università Politecnica delle Marche, Via Conca, 71, 60126, Ancona, Italy. · Dept of Clinical Therapeutics, Alexandra General Hospital, V. Sofias and Lourou 1 11528, Athens, Greece. · Medical Statistics, Trial Center, Fondazione IRCCS Istituto Nazionale Tumori, via G. Venezian 1, 20133, Milano, Italy. · Gastrointestinal Surgery and Liver Transplantation Unit, Fondazione IRCCS Istituto Nazionale Tumori, via G. Venezian 1, 20133, Milano, Italy. ·PLoS One · Pubmed #27064898.

ABSTRACT: Pancreatic metastases from renal cell carcinoma are uncommon and their prognostic significance is not well defined. In this analysis we evaluated the outcome of patients with pancreatic metastases treated with either targeted therapies or local treatment to the pancreas. Patients with pancreatic metastases from renal cell carcinoma treated between 1993 and 2014 were identified from 11 European centers. Clinical records were retrospectively reviewed. Kaplan-Meier method and log-rank test were used to evaluate progression-free survival and overall survival. Cox's proportional hazard models were used for survival analysis. In total, 276 PM patients were evaluated, including 77 (28%) patients treated by either surgery or radiotherapy to the pancreas, and 256 (93%) who received systemic therapy. Median time from nephrectomy to diagnosis of pancreatic metastases was 91 months (IQR 54-142). Disease control rate after first-line TTs was 84%, with a median progression-free survival of 12 months (95% CI 10-14). Median overall survival was 73 months (95% CI 61-86) with a 5-year OS of 58%. Median OS of patients treated with local treatment was 106 months (95% CI 78-204) with a 5-year overall survival of 75%. On multivariable analysis, nephrectomy (HR 5.31; 95%CI 2.36-11.92; p<0.0001), Memorial Sloan Kettering/International Metastatic RCC Database Consortium prognostic score (HR 1.45, 95% CI 0.94-2.23 for intermediate vs good vs risk; HR 2.76 95%, CI 1.43-5.35 for poor vs good risk p = 0.0099) and pancreatic local treatment (HR 0.48; 95%CI 0.30-0.78 p = 0.0029) were associated with overall survival. Difference in median OS between patients with PM and that reported in a matched-control group of mRCC patients with extrapancreatic metastases was statistically significant (p < .0001). Pancreatic metastases from renal cell carcinoma usually occur years after nephrectomy, are associated with an indolent behavior and a prolonged survival. Targeted therapies and locoregional approaches are active and achieve high disease control rate.

13 Article Prognostic role of pancreatic metastases from renal cell carcinoma: results from an Italian center. 2013

Grassi, Paolo / Verzoni, Elena / Mariani, Luigi / De Braud, Filippo / Coppa, Jorgelina / Mazzaferro, Vincenzo / Procopio, Giuseppe. ·Medical Oncology Unit 1, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. ·Clin Genitourin Cancer · Pubmed #23791435.

ABSTRACT: BACKGROUND: Pancreatic metastasis accounts for 2% to 11% of all mRCC cases. The prognostic value of pancreatic metastases in the era of TTs is unclear. We evaluated outcomes in a cohort of mRCC patients with pancreatic metastases (PmRCC) who were treated with TTs. PATIENTS AND METHODS: We retrospectively reviewed the records of 354 mRCC patients treated at our institute between January 2005 and June 2012. Differences in terms of OS between this unselected cohort of mRCC patients and a subgroup of patients with PmRCC were investigated. Kaplan-Meier and log-rank test methods were used to evaluate OS. RESULTS: In total, 24 PmRCC (7%) patients were identified, and were compared with a cohort of 330 mRCC patients with metastasis at other sites. Pancreatic metastases were synchronous in 3 patients, and they were metachronous in 11 patients. Surgical resection of pancreatic metastases was performed in 2 (8%) patients. At a maximum follow-up of 89 months (median, 51 months), median OS was 39 months in PmRCC patients, vs. 23 months in the mRCC patient group (P = .0004). CONCLUSION: Among mRCC patients treated with TTs, the presence of pancreatic metastasis seems to be associated with a longer survival than the presence of metastasis at other sites.

14 Article Multidisciplinary approach for the treatment of neuroendocrine tumors. 2010

de Herder, Wouter W / Mazzaferro, Vincenzo / Tavecchio, Luca / Wiedenmann, Bertram. ·Department of Internal Medicine, Section of Endocrinology Erasmus MC, Rotterdam, The Netherlands. ·Tumori · Pubmed #21302641.

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