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Pancreatic Neoplasms: HELP
Articles by Antongiulio Faggiano
Based on 19 articles published since 2009
(Why 19 articles?)
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Between 2009 and 2019, A. Faggiano wrote the following 19 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Review The management of neuroendocrine tumours: A nutritional viewpoint. 2019

Gallo, Marco / Muscogiuri, Giovanna / Pizza, Genoveffa / Ruggeri, Rosaria Maddalena / Barrea, Luigi / Faggiano, Antongiulio / Colao, Annamaria / Anonymous561555. ·a Oncological Endocrinology Unit, Department of Medical Sciences , University of Turin , AOU Città della Salute e della Scienza di Torino, Turin , Italy. · b Ios and Coleman Medicina Futura Medical Centre , Naples , Italy. · c Unit of Internal Medicine, Landolfi Hospital , Solofra , Avellino , Italy. · d Department of Clinical and Experimental Medicine , Unit of Endocrinology, University of Messina , Messina , Italy. · e Department of Clinical Medicine and Surgery , University "Federico II" of Naples , Naples , Italy. ·Crit Rev Food Sci Nutr · Pubmed #29020456.

ABSTRACT: Nutritional status in patients with neuroendocrine tumours (NETs), especially of gastroenteropancreatic origin, can be deeply affected by excessive production of gastrointestinal hormones, peptides, and amines, which can lead to malabsorption, diarrhoea, steatorrhea, and altered gastrointestinal motility. Besides, the surgical and/or medical management of NETs can lead to alteration of gastrointestinal secretory, motor, and absorptive functions, with both dietary and nutritional consequences. Indeed, disease-related malnutrition is a frequently encountered yet both underrecognized and understudied clinical phenomenon in patients with NETs, with substantial prognostic and socioeconomic consequences. Most of these conditions can be alleviated by a tailored nutritional approach, also with the aim of improving the efficacy of cancer treatments. In this setting, skilled nutritionists can play a fundamental role in the multidisciplinary health care team in NETs management and their presence should be recommended. The aim of this review is to provide dietary advices for each specific condition in patients with NETs, underlining the importance of a nutritional approach to treat malnutrition in this setting. Further, we will provide preliminary evidence coming from our data on the assessment of nutritional status in a single cohort of patients with NETs.

2 Review Diabetes and pancreatic neuroendocrine tumours: Which interplays, if any? 2018

Gallo, Marco / Ruggeri, Rosaria Maddalena / Muscogiuri, Giovanna / Pizza, Genoveffa / Faggiano, Antongiulio / Colao, Annamaria / Anonymous6120946. ·Oncological Endocrinology Unit, Department of Medical Sciences, University of Turin, AOU Città della Salute e della Scienza di Torino, Turin, Italy. Electronic address: mgallo4@cittadellasalute.to.it. · Department of Clinical and Experimental Medicine, Unit of Endocrinology, University of Messina, Italy. · Ios and Coleman Medicina Futura Medical Centre, Naples, Italy. · Unit of Internal Medicine, Landolfi Hospital, Solofra, Avellino, Italy. · Department of Clinical Medicine and Surgery, University "Federico II", Naples, Italy. ·Cancer Treat Rev · Pubmed #29746922.

ABSTRACT: Pancreatic neuroendocrine tumours (PanNETs) represent an uncommon type of pancreatic neoplasm, whose incidence is increasing worldwide. As per exocrine pancreatic cancer, a relationship seems to exist between PanNETs and glycaemic alterations. Diabetes mellitus (DM) or impaired glucose tolerance often occurs in PanNET patients as a consequence of hormonal hypersecretion by the tumour, specifically affecting glucose metabolism, or due to tumour mass effects. On the other hand, pre-existing DM may represent a risk factor for developing PanNETs and is likely to worsen the prognosis of such patients. Moreover, the surgical and/or pharmacological treatment of the tumour itself may impair glucose tolerance, as well as antidiabetic therapies may impact tumour behaviour and patients outcome. Differently from exocrine pancreatic tumours, few data are available for PanNETs as yet on this issue. In the present review, the bidirectional association between glycaemic disorders and PanNETs has been extensively examined, since the co-existence of both diseases in the same individual represents a further challenge for the clinical management of PanNETs.

3 Review The Zollinger-Ellison syndrome: is there a role for somatostatin analogues in the treatment of the gastrinoma? 2018

Guarnotta, Valentina / Martini, Chiara / Davì, Maria Vittoria / Pizza, Genoveffa / Colao, Annamaria / Faggiano, Antongiulio / Anonymous10670923. ·Biomedical Department of Internal and Specialist Medicine (DIBIMIS), Section of Endocrine-Metabolic Diseases, University of Palermo, Palermo, Italy. · Clinica Medica 3^, Department of Medicine, DIMED, University of Padova, Padova, Italy. chiara.martini@aopd.veneto.it. · Section of Endocrinology, Medicina Generale e Malattie Aterotrombotiche e Degenerative, Department of Medicine, University of Verona, Verona, Italy. · Department of Clinical Medicine and Surgery, "Federico II" University of Naples, Naples, Italy. · Thyroid and Parathyroid Surgery Unit, Istituto Nazionale per lo studio e la cura dei tumori "Fondazione G. Pascale" - IRCCS, Naples, Italy. ·Endocrine · Pubmed #29019150.

ABSTRACT: PURPOSE: Analyze the role of somatostatin analogues (SSAs) in the treatment of sporadic and MEN1-related gastrinomas, trying to define whether recent trials have changed the landscape of gastrinoma therapy. METHODS: We evaluate the rationale of SSA use in the treatment of gastrinomas, summarize the current literature concerning the effect of SSAs on the control of Zollinger-Ellison syndrome (ZES) and gastrinomas tumor progression and discuss their role in the most recent guidelines. RESULTS: The medical treatment of gastrinoma and related ZES is aimed at controlling acid hypersecretion and tumor progression, in inoperable patients. The use of proton pump inhibitors (PPIs) to control the syndrome is a cornerstone in the ZES therapy. SSAs are not usually indicated for antisecretory purpose, because PPIs are considered the treatment of choice, due to their long lasting high efficacy and oral availability. The antiproliferative effect of SSAs has been established by two placebo-controlled trials that have clearly demonstrated a significant increase in progression free survival in patients affected by non-functioning well-differentiated advanced neuroendocrine tumors (NETs). The recent ENETS guidelines recommend the use of SSAs in advanced well differentiated NETs as antiproliferative agents. CONCLUSIONS: The high sstr-expression in gastrinomas make them highly responsive to SSAs and support the use of such drugs to counteract the tumour growth in patients not amenable to surgical cure. Unfortunately, limited data, mainly case reports or small series, support the use of SSAs in advanced gastrinomas, therefore, it is difficult to quantify their ability to control tumour growth and disease progression.

4 Review Everolimus as first line therapy for pancreatic neuroendocrine tumours: current knowledge and future perspectives. 2017

Gallo, Marco / Malandrino, Pasqualino / Fanciulli, Giuseppe / Rota, Francesca / Faggiano, Antongiulio / Colao, Annamaria / Anonymous2710903. ·Oncological Endocrinology Unit, Department of Medical Sciences, University of Turin, AOU Città della Salute e della Scienza di Torino, Via Genova 3, 10126, Turin, Italy. mgallo4@cittadellasalute.to.it. · Endocrinology Unit, Garibaldi Nesima Medical Center, Catania, Italy. · Neuroendocrine Tumours Unit, Department of Clinical and Experimental Medicine, University of Sassari, AOU Sassari, Sassari, Italy. · Endocrinology Unit, Regina Elena National Cancer Institute, Rome, Italy. · Thyroid and Parathyroid Surgery Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione G. Pascale", IRCCS, Naples, Italy. · Department of Clinical Medicine and Surgery, University "Federico II", Naples, Italy. ·J Cancer Res Clin Oncol · Pubmed #28405826.

ABSTRACT: PURPOSE: Everolimus has been shown to be effective for advanced pancreatic neuroendocrine tumours (pNETs), but its positioning in the therapeutic algorithm for pNETs is matter of debate. METHODS: With the aim to shed light on this point, we performed an up-to-date critical review taking into account the results of both retrospective and prospective published studies, and the recommendations of international guidelines. In addition, we performed an extensive search on the Clinical Trial Registries databases worldwide, to gather information on the ongoing clinical trials related to this specific topic. RESULTS: We identified eight retrospective published studies, two prospective published studies, and five registered clinical trials. Moreover, we analyzed the content of four widespread international guidelines. CONCLUSIONS: Our critical review confirms the lack of high-quality data to recommend everolimus as the first line therapy for pNETs. The ongoing clinical trials reported in this review will hopefully help clinicians, in the near future, to better evaluate the role of everolimus as the first line therapy for pNETs. However, at the moment, there is already enough evidence to recommend everolimus as the first line therapy for patients with symptomatic malignant unresectable insulin-secreting pNETs, to control the endocrine syndrome regardless of tumour growth.

5 Review Incidence of gastroenteropancreatic neuroendocrine tumours: a systematic review of the literature. 2014

Fraenkel, M / Kim, M / Faggiano, A / de Herder, W W / Valk, G D / Anonymous2690778. ·Endocrinology, Soroka University Medical Center and the Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheeba, Israel Mount Sinai Medical Center, New York, New York, USA Department of Clinical Medicine and Surgery, University Federico II, Naples, Italy Endocrinology, National Cancer Institute, Fondazione G. Pascale, Naples, Italy Erasmus MC, Rotterdam, The Netherlands Department of Internal Medicine, Division of Gastroenterology, University Medical Center Utrecht, Utrecht, The Netherlands. ·Endocr Relat Cancer · Pubmed #24322304.

ABSTRACT: Based on the current medical literature, the worldwide incidence of neuroendocrine tumours (NETs) seems to have increased; however, a systematic literature overview is lacking. This study aimed to collect all available data on the incidence of gastroenteropancreatic (GEP)-NETs and characteristics of population to establish their epidemiology. A sensitive MEDLINE search was carried out. The papers were selected via a cascade process that restricted the initial pool of 7991 articles to 33, using predefined inclusion and exclusion criteria. Original articles evaluating the incidence of sporadic GEP-NETs in regional, institutional and national registries were considered. The majority of data originated from the US National Cancer Institute Surveillance, Epidemiology and End Results database and from national cancer registries in Western Europe. Generally, because of the retrospective nature of existing databases the outcomes of studies might be biased, which hinders the drawing of firm conclusions. The age-adjusted incidence of GEP-NETs has increased steadily over the past four decades (1973-2007), increasing 3.65-fold in the USA and 3.8- to 4.8-fold in the UK. Incidence has changed variably from one anatomical site to another. The greatest increase in incidence occurred for gastric and rectal NETs, while the smallest increase occurred for small intestine NETs. There were gender and racial differences, which differed site by site and, in some cases, changed over time. The incidence rates (IRs) of GEP-NETs have increased significantly in the last 40 years. Data are only available from North America, Western Europe and Japan. A site-by-site analysis revealed that the IRs of some NETs increased more than those of others.

6 Review Epidemiology of gastroenteropancreatic neuroendocrine tumours. 2012

Fraenkel, M / Kim, M K / Faggiano, A / Valk, G D. ·Endocrinology Unit, Soroka University Medical Center and the Faculty of Health Sciences, Ben-Gurion University of the Negev, Yitzchag Rager, Beer Sheva, Israel. meravfra@gmail.com ·Best Pract Res Clin Gastroenterol · Pubmed #23582913.

ABSTRACT: Gastroenteropancreatic neuroendocrine tumours are a heterogeneous group of tumours arising from diffuse endocrine cells, causing unique clinical syndromes. These tumours, formerly named carcinoid, can involve any part of the gastrointestinal tract and the endocrine pancreas and have a wide range of malignant potential: from benign to poorly differentiated tumours. In this review we will summarize the data available on the epidemiology of gastroenteropancreatic tumours as it is reported from around the world. This includes annual incidence rates at the various anatomic sites, and trends in incidence rates with time. In addition age and stage at presentation, gender and racial differences and finally prognosis and survival were collected when reported.

7 Clinical Trial Real-world study of everolimus in advanced progressive neuroendocrine tumors. 2014

Panzuto, Francesco / Rinzivillo, Maria / Fazio, Nicola / de Braud, Filippo / Luppi, Gabriele / Zatelli, Maria Chiara / Lugli, Francesca / Tomassetti, Paola / Riccardi, Ferdinando / Nuzzo, Carmen / Brizzi, Maria Pia / Faggiano, Antongiulio / Zaniboni, Alberto / Nobili, Elisabetta / Pastorelli, Davide / Cascinu, Stefano / Merlano, Marco / Chiara, Silvana / Antonuzzo, Lorenzo / Funaioli, Chiara / Spada, Francesca / Pusceddu, Sara / Fontana, Annalisa / Ambrosio, Maria Rosaria / Cassano, Alessandra / Campana, Davide / Cartenì, Giacomo / Appetecchia, Marialuisa / Berruti, Alfredo / Colao, Annamaria / Falconi, Massimo / Delle Fave, Gianfranco. ·Digestive and Liver Disease, Sapienza University of Rome, Sant'Andrea Hospital, Rome, Italy; Unit of Gastrointestinal and Neuroendocrine Tumors, European Institute of Oncology, Milan, Italy; Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy; Oncology and Hematology, Policlinico di Modena, Italy; Section of Endocrinology and Internal Medicine, Department of Medical Sciences, University of Ferrara, Ferrara, Italy; Departments of Endocrinology and Oncologia Medica, Università Cattolica del S. Cuore, Rome, Italy; Departments of Medical and Surgical Sciences and Medical Oncology, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy; Oncology, Antonio Cardarelli Hospital, Naples, Italy; Division of Medical Oncology and Endocrinology Unit, Regina Elena National Cancer Institute Rome, IRCCS, Rome, Italy; Oncology, San Luigi Gonzaga Hospital, Orbassano, Torino, Italy; Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples, Italy; Oncology, Fondazione Poliambulanza, Brescia, Italy; Oncology, Istituto Oncologico Veneto, Padova, Italy; Departments of Medical Oncology and Pancreatic Surgery, AOU Ospedali Riuniti, Università Politecnica delle Marche, Ancona, Italy; Oncology, S. Croce e Carle Hospital, Cuneo, Italy; Department of Medical Oncology A, IRCCS AOU San Martino-IST, Genova, Italy; Oncologia Medica 1, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy; Oncology, Niguarda Cancer Center, Ospedale Niguarda Ca' Granda, Milan, Italy; Oncologia, Spedali Civili di Brescia, University of Brescia, Brescia, Italy. · Digestive and Liver Disease, Sapienza University of Rome, Sant'Andrea Hospital, Rome, Italy; Unit of Gastrointestinal and Neuroendocrine Tumors, European Institute of Oncology, Milan, Italy; Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy; Oncology and Hematology, Policlinico di Modena, Italy; Section of Endocrinology and Internal Medicine, Department of Medical Sciences, University of Ferrara, Ferrara, Italy; Departments of Endocrinology and Oncologia Medica, Università Cattolica del S. Cuore, Rome, Italy; Departments of Medical and Surgical Sciences and Medical Oncology, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy; Oncology, Antonio Cardarelli Hospital, Naples, Italy; Division of Medical Oncology and Endocrinology Unit, Regina Elena National Cancer Institute Rome, IRCCS, Rome, Italy; Oncology, San Luigi Gonzaga Hospital, Orbassano, Torino, Italy; Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples, Italy; Oncology, Fondazione Poliambulanza, Brescia, Italy; Oncology, Istituto Oncologico Veneto, Padova, Italy; Departments of Medical Oncology and Pancreatic Surgery, AOU Ospedali Riuniti, Università Politecnica delle Marche, Ancona, Italy; Oncology, S. Croce e Carle Hospital, Cuneo, Italy; Department of Medical Oncology A, IRCCS AOU San Martino-IST, Genova, Italy; Oncologia Medica 1, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy; Oncology, Niguarda Cancer Center, Ospedale Niguarda Ca' Granda, Milan, Italy; Oncologia, Spedali Civili di Brescia, University of Brescia, Brescia, Italy gianfranco.dellefave@uniroma1.it. ·Oncologist · Pubmed #25117065.

ABSTRACT: Everolimus is a valid therapeutic option for neuroendocrine tumors (NETs); however, data in a real-world setting outside regulatory trials are sparse. The aim of this study was to determine everolimus tolerability and efficacy, in relation to previous treatments, in a compassionate use program. A total of 169 patients with advanced progressive NETs treated with everolimus were enrolled, including 85 with pancreatic NETs (pNETs) and 84 with nonpancreatic NETs (non-pNETs). Previous treatments included somatostatin analogs (92.9%), peptide receptor radionuclide therapy (PRRT; 50.3%), chemotherapy (49.7%), and PRRT and chemotherapy (22.8%). Overall, 85.2% of patients experienced adverse events (AEs), which were severe (grade 3-4) in 46.1%. The most frequent severe AEs were pneumonitis (8.3%), thrombocytopenia (7.7%), anemia (5.3%), and renal failure (3.5%). In patients previously treated with PRRT and chemotherapy, a 12-fold increased risk for severe toxicity was observed, with grade 3-4 AEs reported in 86.8% (vs. 34.3% in other patients). In addition, 63.3% of patients required temporarily everolimus discontinuation due to toxicity. Overall, 27.8% of patients died during a median follow-up of 12 months. Median progression-free survival (PFS) and overall survival (OS) were 12 months and 32 months, respectively. Similar disease control rates, PFS, and OS were reported in pNETs and non-pNETs. In the real-world setting, everolimus is safe and effective for the treatment of NETs of different origins. Higher severe toxicity occurred in patients previously treated with systemic chemotherapy and PRRT. This finding prompts caution when using this drug in pretreated patients and raises the issue of planning for everolimus before PRRT and chemotherapy in the therapeutic algorithm for advanced NETs.

8 Article Impact of Nutritional Status on Gastroenteropancreatic Neuroendocrine Tumors (GEP-NET) Aggressiveness. 2018

Barrea, Luigi / Altieri, Barbara / Muscogiuri, Giovanna / Laudisio, Daniela / Annunziata, Giuseppe / Colao, Annamaria / Faggiano, Antongiulio / Savastano, Silvia. ·Dipartimento di Medicina Clinica e Chirurgia, Unit of Endocrinology, Federico II University Medical School of Naples, Via Sergio Pansini, 5, 80131 Naples, Italy. luigi.barrea@unina.it. · Dipartimento di Medicina Clinica e Chirurgia, Unit of Endocrinology, Federico II University Medical School of Naples, Via Sergio Pansini, 5, 80131 Naples, Italy. altieri.barbara@gmail.com. · Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Hospital, University of Wuerzburg, 97080 Wuerzburg, Germany. altieri.barbara@gmail.com. · Dipartimento di Medicina Clinica e Chirurgia, Unit of Endocrinology, Federico II University Medical School of Naples, Via Sergio Pansini, 5, 80131 Naples, Italy. giovanna.muscogiuri@gmail.com. · Dipartimento di Medicina Clinica e Chirurgia, Unit of Endocrinology, Federico II University Medical School of Naples, Via Sergio Pansini, 5, 80131 Naples, Italy. daniela.laudisio@libero.it. · Department of Pharmacy, University of Naples "Federico II", Italy; Via Domenico Montesano, 49, 80131 Naples, Italy. giuseppe.annunziata@unina.it. · Dipartimento di Medicina Clinica e Chirurgia, Unit of Endocrinology, Federico II University Medical School of Naples, Via Sergio Pansini, 5, 80131 Naples, Italy. colao@unina.it. · Dipartimento di Medicina Clinica e Chirurgia, Unit of Endocrinology, Federico II University Medical School of Naples, Via Sergio Pansini, 5, 80131 Naples, Italy. afaggian@unina.it. · Dipartimento di Medicina Clinica e Chirurgia, Unit of Endocrinology, Federico II University Medical School of Naples, Via Sergio Pansini, 5, 80131 Naples, Italy. sisavast@unina.it. ·Nutrients · Pubmed #30513732.

ABSTRACT: Neuroendocrine tumors (NETs) are rare neoplasms mostly originating from the gastroenteropancreatic tract (GEP-NETs). Data regarding nutritional status in GEP-NET patients are limited. The aim of the study was to investigate the nutritional status and adherence to the Mediterranean Diet (MD) in GEP-NET patients and to correlate them with tumor aggressiveness. A cross-sectional case-control observational study was conducted enrolling 83 patients with well-differentiated G1/G2 GEP-NETs after resection, as well as 83 healthy subjects, age, sex and body mass index-matched. Nutritional status was assessed by evaluating with Bioelectrical Impedance analysis and its phase angle (PhA), adherence to the MD according to PREDIMED score, dietary assessment, anthropometric parameters, and clinico-pathological characteristics. GEP-NET patients consumed less frequently vegetables, fruits, wine, fish/seafood, nuts, and more frequently red/processed meats, butter, cream, margarine, and soda drinks than controls. Patients with more aggressive disease presented a lower adherence to MD according to PREDIMED categories in comparison to G1, localized and free/stable disease status. A smaller PhA value and a lower PREDIMED score were significantly correlated with G2 tumor, metastases, and progressive disease. To the best of our knowledge, this is the first study reporting an association between nutritional status and tumor aggressiveness in a selected group of GEP-NETs. Moreover, higher intakes of food of MD, may represent a potential tool for prevention of tumor aggressiveness. Thus, a skilled nutritionist should be an integral part of the multidisciplinary management of GEP-NET patients.

9 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.

10 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.

11 Article Role of contrast-enhanced ultrasound to define prognosis and predict response to biotherapy in pancreatic neuroendocrine tumors. 2017

Del Prete, M / Di Sarno, A / Modica, R / Lassandro, F / Giorgio, A / Bianco, A / Muto, M / Gasperi, M / Del Prete, F / Colao, A / Montesarchio, V / Faggiano, A / Anonymous5830911. ·Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy. michidelpre@gmail.com. · UOC of Oncology, A.O. dei Colli, Monaldi Unit, Naples, Italy. · Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy. · UOC of Radiology, A.O. dei Colli, Monaldi Unit, Naples, Italy. · Interventional Unit Ultrasound, A.O. dei Colli, D. Cotugno Unit, Naples, Italy. · Department of Medicine and Health Sciences, Section of Endocrinology, University of Molise, Campobasso, Italy. · Centre for Economic and International Studies, University of Rome "Tor Vergata", Rome, Italy. · Thyroid and Parathyroid Surgery Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione G. Pascale"-IRCCS, Naples, Italy. ·J Endocrinol Invest · Pubmed #28667452.

ABSTRACT: PURPOSE: The incidence of neuroendocrine tumors (NETs) is progressively increasing. Most cases arise from the digestive system, where ileum, rectum and pancreas represent the commonest site of origin. Liver metastases are frequently detected at diagnosis or during the follow-up. Contrast-enhanced ultrasound (CEUS) is used in patients with pancreatic NETs (P-NETs) and liver metastases from P-NET but its role has not been standardized. The aim of this retrospective study was to investigate CEUS in patients with P-NETs and liver metastases from P-NET both as prognostic factor and predictor of response to therapy with somatostatin analogues (SSAs). METHODS: CEUS was performed at the diagnosis of NET and 3, 6 and 12 months after the beginning of SSAs. CEUS pattern was compared with contrast-enhanced computed tomography (CT) pattern. RESULTS: There was a significant association between CEUS and CT pattern (X CONCLUSIONS: In patients with P-NET, CEUS pattern correlates with tumor grading, being homogeneous in G1-G2 but not in G3 tumors. After therapy with SSAs, CEUS is predictive of response to SSAs. These findings seem to support a role of CEUS as prognostic and predictive factor of response.

12 Article Italian Association of Clinical Endocrinologists (AME) position statement: a stepwise clinical approach to the diagnosis of gastroenteropancreatic neuroendocrine neoplasms. 2014

Grimaldi, Franco / Fazio, Nicola / Attanasio, Roberto / Frasoldati, Andrea / Papini, Enrico / Angelini, Francesco / Baldelli, Roberto / Berretti, Debora / Bianchetti, Sara / Bizzarri, Giancarlo / Caputo, Marco / Castello, Roberto / Cremonini, Nadia / Crescenzi, Anna / Davì, Maria Vittoria / D'Elia, Angela Valentina / Faggiano, Antongiulio / Pizzolitto, Stefano / Versari, Annibale / Zini, Michele / Rindi, Guido / Oberg, Kjell. ·Endocrinology and Metabolic Disease Unit, Azienda Ospedaliero-Universitaria "S. Maria della Misericordia", P.le S.M. della Misericordia, 15-33100, Udine, Italy, franco.grimaldi@aliceposta.it. ·J Endocrinol Invest · Pubmed #25038902.

ABSTRACT: -- No abstract --

13 Article Combined biological therapy with lanreotide autogel and cabergoline in the treatment of MEN-1-related insulinomas. 2014

Marciello, Francesca / Di Somma, Carolina / Del Prete, Michela / Marotta, Vincenzo / Ramundo, Valeria / Carratù, Annachiara / de Luca di Roseto, Chiara / Camera, Luigi / Colao, Annamaria / Faggiano, Antongiulio. ·Division of Endocrinology, Department of Clinical Medicine and Surgery, University of Naples "Federico II", Naples, Italy, francesca.marciello@libero.it. ·Endocrine · Pubmed #24385268.

ABSTRACT: Multiple endocrine neoplasia type 1 (MEN1) is a hereditary syndrome associated with the development of many endocrine tumors, involving mainly pituitary, parathyroids, pancreas, although a proliferative state interests all neuroendocrine system. MEN1 pancreatic neuroendocrine tumors (pNETs) are multiples and can secrete different hormones. The therapeutic approach is based on surgery which usually is followed by tumor relapse or persistence unless to be highly aggressive. Biotherapy with somatostatin analogs and dopamine agonists could be of great benefit to manage these patients without altering their life quality. We report a case of a 36-year-old MEN1 man affected with multicentric pNETs associated with insulinoma syndrome. Therapy with symptomatic agents (diazoxide), as well as biotherapy (lanreotide, cabergoline) was started. At 6-month follow-up, symptomatic agents were stopped and disease control was only based on lanreotide plus cabergoline. This combined biotherapy was able to control endocrine syndromes and tumor growth. Subsequently, a safer and selective surgical intervention on pNETs was performed. An excellent response to therapy with lanreotide autogel and cabergoline has been observed in a MEN1 patient with pNETs associated with insulinoma syndrome. The potential synergistic effects of lanreotide autogel and cabergoline on insulin-secreting neuroendocrine tumors are discussed.

14 Article Transarterial embolization (TAE) is equally effective and slightly safer than transarterial chemoembolization (TACE) to manage liver metastases in neuroendocrine tumors. 2014

Fiore, Francesco / Del Prete, Michela / Franco, Renato / Marotta, Vincenzo / Ramundo, Valeria / Marciello, Francesca / Di Sarno, Antonella / Carratù, Anna Chiara / de Luca di Roseto, Chiara / Colao, Annamaria / Faggiano, Antongiulio. ·Interventional Radiology, National Cancer Institute, Fondazione "G. Pascale", Naples, Italy, doc.fiore@virgilio.it. ·Endocrine · Pubmed #24385266.

ABSTRACT: Liver metastases from neuroendocrine tumor (NET) can be treated by transarterial embolization (TAE) or transarterial chemoembolization (TACE). The goal of TAE and TACE is to reduce blood flow to the tumor resulting in tumor ischemia and necrosis. In this retrospective study, the effectiveness and safety of TAE-TACE in the treatment of liver metastases in patients with NET was compared. Thirty patients with a histologically confirmed gastro-entero-pancreatic NET with liver metastases were retrospectively investigated. Seventeen patients underwent TAE, while 13 patients underwent TACE. Tumor response, degree of devascularization in treated lesions, and progression free survival (PFS) were evaluated in the whole population and then separately in TAE and TACE subgroups. In all patients treated with TAE and TACE, there was a significant size reduction of lesions as compared to baseline. Per lesion reduction was 2.2 ± 1.4 versus 3.3 ± 1.5 cm for TAE (p < 0.001) and 2.2 ± 1.5 versus 3.4 ± 1.7 cm for TACE (p < 0.001). In the whole population, the median PFS for all patients was 36 months (16.2-55.7 CI), without significant difference between TAE and TACE. In no patient did adverse events grade 3 and 4 as well as TAE/TACE-related death occurred, while the post-embolization syndrome occurred in 41 % of patients treated with TAE and 61 % of those treated with TACE. TAE and TACE are both effective in NET patients with liver metastases. TAE should be preferred to TACE in light of its similar anti-tumor effects and slightly better toxicity profile.

15 Article Assessment and clinical implications of RANK/RANKL/OPG pathway as markers of bone tumor progression in patients with NET harboring bone metastases. 2013

Milone, F / Pivonello, C / Cariati, F / Sarnataro, M / Ramundo, V / Marotta, V / Jann, H / Pape, U-F / Wiedenmann, B / Colao, A / Pavel, M / Faggiano, A. ·Department of Molecular and Clinical Endocrinology and Oncology, Federico II University, Naples, Italy. ·Biomarkers · Pubmed #23336103.

ABSTRACT: INTRODUCTION: The impact on the survival of bone metastases (BM) in patients with neuroendocrine tumor (NET) is a matter of debate. BM have a key role in causing symptoms and in decreasing patients' quality of life. Although the mechanisms of the development of BM are not completely clear, it is now well understood that the Receptor Activator of Nuclear factor Kappa-B-/Ligand (RANK/RANKL)/osteoprotegerin (OPG) pathway plays a relevant role. AIM: To characterize the RANK/RANKL/OPG pathway in patients affected with NET. PATIENTS AND METHODS: Two cohorts of 15 patients each were enrolled in the study; one cohort was affected with NET without BM and the second cohort was affected with NET with BM. The serum RANK/RANKL/OPG pathway was assessed in both the groups. RESULTS: Serum OPG levels and RANKL/OPG ratio were lower and higher, respectively, in NET patients harboring BM than in those without BM. During the ROC analysis, a cut-off value of 1071 pg/ml for OPG and 0.62 for RANKL/OPG ratio were able to significantly distinguish between the two groups. CONCLUSIONS: This study indicates that RANK/RANKL/OPG pathway is imbalanced in patients with NET harboring BM. Specific alterations of this pathway could predict an early development of BM.

16 Article Limitations of Chromogranin A in clinical practice. 2012

Marotta, Vincenzo / Nuzzo, Vincenzo / Ferrara, Teresa / Zuccoli, Alfonso / Masone, Milena / Nocerino, Lorenzo / Del Prete, Michela / Marciello, Francesca / Ramundo, Valeria / Lombardi, Gaetano / Vitale, Mario / Colao, Annamaria / Faggiano, Antongiulio. ·Department of Molecular and Clinical Endocrinology and Oncology, Federico II University of Naples, Italy. ·Biomarkers · Pubmed #22303881.

ABSTRACT: CONTEXT: Usefulness of circulating Chromogranin A (CgA) for the diagnosis of neuroendocrine tumors (NEN) is controversial. The aim of the present study was to assess the actual role of this marker as diagnostic tool. METHODS: Serum blood samples were obtained from 42 subjects affected with NEN, 120 subjects affected with non-endocrine neoplasias (non-NEN) and 100 non-neoplastic subjects affected with benign nodular goitre (NNG). Determination of CgA was performed by means of immunoradiometric assay. RESULTS: The CgA levels among NEN-patients were not significantly different from NNG and non-NEN subjects. The Receiver operating characteristic (ROC) curves analysis failed to identify a feasible cut-off value for the differential diagnosis between NEN and the other conditions. CONCLUSION: Serum CgA is not helpful for the first-line diagnosis of NEN.

17 Article Natural history of gastro-entero-pancreatic and thoracic neuroendocrine tumors. Data from a large prospective and retrospective Italian epidemiological study: the NET management study. 2012

Faggiano, A / Ferolla, P / Grimaldi, F / Campana, D / Manzoni, M / Davì, M V / Bianchi, A / Valcavi, R / Papini, E / Giuffrida, D / Ferone, D / Fanciulli, G / Arnaldi, G / Franchi, G M / Francia, G / Fasola, G / Crinò, L / Pontecorvi, A / Tomassetti, P / Colao, A. ·Department of Molecular and Clinical Endocrinology and Oncology, Section of Endocrinology, University of Naples "Federico II", Italy. ·J Endocrinol Invest · Pubmed #22080849.

ABSTRACT: BACKGROUND: The few epidemiological data available in literature on neuroendocrine tumors (NET) are mainly based on Registry databases, missing therefore details on their clinical and natural history. AIM: To investigate epidemiology, clinical presentation, and natural history of NET. DESIGN AND SETTING: A large national retrospective survey was conducted in 13 Italian referral centers. Among 1203 NET, 820 originating in the thorax (T-NET), in the gastro-enteropancreatic tract (GEP-NET) or metastatic NET of unknown primary origin (U-NET) were enrolled in the study. RESULTS: 93% had a sporadic and 7% a multiple endocrine neoplasia type 1 (MEN1)-associated tumor; 63% were GEP-NET, 33% T-NET, 4% U-NET. Pancreas and lung were the commonest primary sites. Poorly differentiated carcinomas were <10%, all sporadic. The incidence of NET had a linear increase from 1990 to 2007 in all the centers. The mean age at diagnosis was 60.0 ± 16.4 yr, significantly anticipated in MEN1 patients (47.7 ± 16.5 yr). Association with cigarette smoking and other non-NET cancer were more prevalent than in the general Italian population. The first symptoms of the disease were related to tumor burden in 46%, endocrine syndrome in 23%, while the diagnosis was fortuity in 29%. Insulin (37%) and serotonin (35%) were the most common hormonal hypersecretions. An advanced tumor stage was found in 42%, more frequently in the gut and thymus. No differences in the overall survival was observed between T-NET and GEP-NET and between sporadic and MEN1-associated tumors at 10 yr from diagnosis, while survival probability was dramatically reduced in U-NET. CONCLUSIONS: The data obtained from this study furnish relevant information on epidemiology, natural history, and clinico-pathological features of NET, not available from the few published Register studies.

18 Article Screening of pancreaticoduodenal endocrine tumours in patients with MEN 1: multidetector-row computed tomography vs. endoscopic ultrasound. 2011

Camera, L / Paoletta, S / Mollica, C / Milone, F / Napolitano, V / De Luca, L / Faggiano, A / Colao, A / Salvatore, M. ·Dipartimento di Scienze Bio-Morfologiche e Funzionali, Sez. di Diagnostica per Immagini e Radioterapia (Ed. 10), Università degli Studi di Napoli Federico II, Via S. Pansini 5, 80131, Napoli, Italy. camera@unina.it ·Radiol Med · Pubmed #21286942.

ABSTRACT: PURPOSE: The authors compared multidetector-row computed tomography (MDCT) and endoscopic ultrasound (EUS) in the identification of pancreaticoduodenal endocrine tumours (PETs) in patients with multiple endocrine neoplasia type 1 (MEN 1). MATERIALS AND METHODS: Fourteen consecutive patients (eight men and six women, aged 26-54 years) with MEN 1 underwent MDCT performed with a 4- (n=5) or 64- (n=9) detector-row system and EUS done with a radial transducer (7.5-20 MHz) within 7-28 days of each other. Prior to MDCT examination, patients were given 750 cc of water and asked to lie down in the right lateral decubitus for 15 min. Multiphase MDCT images were acquired both before and after the injection of nonionic iodinated contrast material (2 cc/kg) at an injection rate of 4 ml/s, with technical parameters and scan delay varying in relation to the system used. Images were all reconstructed at 3-mm intervals for the three phases (arterial, pancreatic and portal) and evaluated on a dedicated workstation. RESULTS: MDCT detected a total of 25 PETs (3-18 mm) in nine patients. Of these lesions, nine were situated within the duodenal wall and 16 in either the pancreatic head (n=3), body (n=7), or tail (n=6). Three additional lesions were detected retrospectively after EUS imaging. Most (18/22, 81%) were hypervascular nodules, and four appeared as either hypoattenuating or cystic lesions. EUS detected a total of 32 PETs (2-18 mm) in 11 patients. Most lesions (29/32, 90%) appeared hypoechoic and were situated in the duodenal wall (n=15) or in either the pancreatic head (n=10), body (n=6) or tail (n=1). CONCLUSIONS: Our preliminary data indicate that MDCT is complementary to EUS in the identification of PETs in MEN-1 patients.

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.