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Pancreatic Neoplasms: HELP
Articles by Anna Maria Colao
Based on 27 articles published since 2009
(Why 27 articles?)
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Between 2009 and 2019, A. Colao wrote the following 27 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Review Bone Metastases in Neuroendocrine Neoplasms: From Pathogenesis to Clinical Management. 2019

Altieri, Barbara / Di Dato, Carla / Martini, Chiara / Sciammarella, Concetta / Di Sarno, Antonella / Colao, Annamaria / Faggiano, Antongiulio / Anonymous5721562. ·Department of Clinical Medicine and Surgery, Federico II University, 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. · Department of Clinical Medicine, Bufalini Hospital, 47521 Cesena, Italy. didatocarla@gmail.com. · Clinica Medica 3, Department of Medicine, DIMED, University of Padova, 35128 Padova, Italy. chiara.martini@aopd.veneto.it. · Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, 37126 Verona, Italy. concetta.sciammarella@alice.it. · UOC of Oncology, AO dei Colli, Monaldi Unit, 80131 Naples, Italy. antonella.disarno@gmail.com. · Department of Clinical Medicine and Surgery, Federico II University, 80131 Naples, Italy. colao@unina.it. · Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy. antongiulio.faggiano@uniroma1.it. · Department of Clinical Medicine and Surgery, Federico II University, 80131 Naples, Italy. ·Cancers (Basel) · Pubmed #31500357.

ABSTRACT: Bone represents a common site of metastases for several solid tumors. However, the ability of neuroendocrine neoplasms (NENs) to localize to bone has always been considered a rare and late event. Thanks to the improvement of therapeutic options, which results in longer survival, and of imaging techniques, particularly after the introduction of positron emission tomography (PET) with gallium peptides, the diagnosis of bone metastases (BMs) in NENs is increasing. The onset of BMs can be associated with severe skeletal complications that impair the patient's quality of life. Moreover, BMs negatively affect the prognosis of NEN patients, bringing out the lack of curative treatment options for advanced NENs. The current knowledge on BMs in gastro-entero-pancreatic (GEP) and bronchopulmonary (BP) NENs is still scant and is derived from a few retrospective studies and case reports. This review aims to perform a critical analysis of the evidence regarding the role of BMs in GEP- and BP-NENs, focusing on the molecular mechanisms underlining the development of BMs, as well as clinical presentation, diagnosis, and treatment of BMs, in an attempt to provide suggestions that can be used in clinical practice.

2 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.

3 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.

4 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.

5 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.

6 Review Vitamin D and pancreas: The role of sunshine vitamin in the pathogenesis of diabetes mellitus and pancreatic cancer. 2017

Altieri, Barbara / Grant, William B / Della Casa, Silvia / Orio, Francesco / Pontecorvi, Alfredo / Colao, Annamaria / Sarno, Gerardo / Muscogiuri, Giovanna. ·a Institute of Medical Pathology, Division of Endocrinology and Metabolic Diseases, Catholic University of the Sacred Heart , Rome , Italy. · b Sunlight , Nutrition, and Health Research Center , San Francisco , California , USA. · c Endocrinology, Department of Sports Science and Wellness , Parthenope University , Naples , Italy. · d Fertility Techniques SSD , San Giovanni di Dio e Ruggi D'Aragona University Hospital , Salerno , Italy. · e Department of Clinical Medicine and Surgery, Section of Endocrinology , University "Federico II," Naples , Italy. · f Department of General Surgery and Transplantation Unit , San Giovanni di Dio e Ruggi D'Aragona University Hospital, Scuola Medica Salernitana , Salerno , Italy. · g Ios and Coleman Medicina Futura Medical Center , Naples , Italy. ·Crit Rev Food Sci Nutr · Pubmed #27030935.

ABSTRACT: Increasing evidence suggests that vitamin D exerts multiple effects beyond bone and calcium metabolism. Vitamin D seems to play a role in pancreatic disease, including type 1 and type 2 diabetes mellitus as well as pancreatic cancer. Vitamin D's immune-modulatory action suggests that it could help prevent type 1 diabetes. In type 2 diabetes, vitamin D may influence β-cell function, insulin sensitivity, and systematic inflammation-all characteristic pathways of that disease. Data from observational studies correlated vitamin D deficiency with risk of type 1 and type 2 diabetes. Prospective and ecological studies of pancreatic cancer incidence generally support a beneficial effect of higher 25-hydroxyvitamin D concentration as well as inverse correlations between UVB dose or exposure and incidence and/or mortality rate of pancreatic cancer. This review discusses the literature regarding vitamin D's role in risk of diabetes and pancreatic cancer. The results to date generally satisfy Hill's criteria for causality regarding vitamin D and incidence of these pancreatic diseases. However, large randomized, blinded, prospective studies are required to more fully evaluate the potential therapeutic role of vitamin D in preventing pancreatic diseases.

7 Review Efficacy and Safety of Everolimus in Extrapancreatic Neuroendocrine Tumor: A Comprehensive Review of Literature. 2016

Faggiano, Antongiulio / Malandrino, Pasqualino / Modica, Roberta / Agrimi, Daniela / Aversano, Maurizio / Bassi, Vincenzo / Giordano, Ernesto A / Guarnotta, Valentina / Logoluso, Francesco A / Messina, Erika / Nicastro, Vincenzo / Nuzzo, Vincenzo / Sciaraffia, Marcello / Colao, Annamaria. ·Thyroid and Parathyroid Surgery Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione G. Pascale" - IRCCS, Naples, Italy afaggian@unina.it. · Endocrinology Unit, Garibaldi Nesima Medical Center, Catania, Italy. · Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy. · District Hospital, Azienda Sanitaria Locale, Brindisi, Italy. · Endocrinology Unit, Azienda Sanitaria Locale Napoli 3, Naples, Italy. · Unit of Internal Medicine, San Giovanni Bosco Hospital, Naples, Italy. · Endocrinology Unit, Azienda Sanitaria Provinciale di Calabria, Reggio Calabria, Italy. · Biomedical Department of Internal and Specialist Medicine, Section of Endocrinology, University of Palermo, Palermo, Italy. · Endocrinology Unit, Azienda Ospedaliero-Universitaria Consorziale Policlinico, Bari, Italy. · Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy. · Azienda Ospedaliero-Universitaria "Ospedali Riuniti," Foggia, Italy. · Unit of Internal Medicine, San Gennaro Hospital, Naples, Italy. · Endocrinology Unit, SS Annunziata Hospital, Taranto, Italy. ·Oncologist · Pubmed #27053503.

ABSTRACT: BACKGROUND: Everolimus, an oral mTOR (mammalian target of rapamycin) inhibitor, is currently approved for the treatment of progressive pancreatic neuroendocrine tumors (NETs). Although promising, only scattered data, often from nondedicated studies, are available for extrapancreatic NETs. PATIENTS AND METHODS: A systematic review of the published data was performed concerning the use of everolimus in extrapancreatic NET, with the aim of summarizing the current knowledge on its efficacy and tolerability. Moreover, the usefulness of everolimus was evaluated according to the different sites of the primary. RESULTS: The present study included 22 different publications, including 874 patients and 456 extrapancreatic NETs treated with everolimus. Nine different primary sites of extrapancreatic NETs were found. The median progression-free survival ranged from 12.0 to 29.9 months. The median time to progression was not reached in a phase II prospective study, and the interval to progression ranged from 12 to 36 months in 5 clinical cases. Objective responses were observed in 7 prospective studies, 2 retrospective studies, and 2 case reports. Stabilization of the disease was obtained in a high rate of patients, ranging from 67.4% to 100%. The toxicity of everolimus in extrapancreatic NETs is consistent with the known safety profile of the drug. Most adverse events were either grade 1 or 2 and easy manageable with a dose reduction or temporary interruption and only rarely requiring discontinuation. CONCLUSION: Treatment with everolimus in patients with extrapancreatic NETs appears to be a promising strategy that is safe and well tolerated. The use of this emerging opportunity needs to be validated with clinical trials specifically designed on this topic. IMPLICATIONS FOR PRACTICE: The present study reviewed all the available published data concerning the use of everolimus in 456 extrapancreatic neuroendocrine tumors (NETs) and summarized the current knowledge on the efficacy and safety of this drug, not yet approved except for pancreatic NETs. The progression-free survival rates and some objective responses seem promising and support the extension of the use of this drug. The site-by-site analysis seems to suggest that some subtypes of NETs, such as colorectal, could be more sensitive to everolimus than other primary NETs. No severe adverse events were usually reported and discontinuation was rarely required; thus, everolimus should be considered a valid therapeutic option for extrapancreatic NETs.

8 Review Combined treatment with PPAR-γ agonists in pancreatic cancer: a glimmer of hope for cancer therapy? 2013

Dicitore, Alessandra / Caraglia, Michele / Colao, Annamaria / Zappavigna, Silvia / Mari, Daniela / Hofland, Leo J / Persani, Luca / Vitale, Giovanni. ·Laboratory of Experimental Endocrinology, Istituto Auxologico Italiano IRCCS, Milan, Italy. ·Curr Cancer Drug Targets · Pubmed #23617255.

ABSTRACT: Pancreas cancer is the fourth leading cause of cancer death due to the limited treatment success rate. The wide number of signalling pathway aberrations contributing to tumorigenesis, progression and drug resistance, is the main reason for unsuccessful treatments in pancreatic cancer. An additional and still under-investigated intracellular cancer target is the peroxisome proliferator activated receptor gamma (PPAR-γ). Several studies have shown the in vitro antitumor activity of PPAR-γ agonists in cancer cells but, if used in monotherapy, they were poorly effective in cancer treatment. The present review will focus on the potential therapeutic role of PPAR-γ agonists in combination with other drugs (type I interferons, gemcitabine and COX-2 inhibitors), highlighting molecular interactions and signalling pathways involved in pancreatic cancer cells. Understanding of the underlying molecular mechanisms and survival pathways activated in cancer cells should promote the development of more successful strategies based on the specific targeting of molecular pathways involved in the resistance to anti-cancer agents.

9 Review Metabolic syndrome and risk of cancer: a systematic review and meta-analysis. 2012

Esposito, Katherine / Chiodini, Paolo / Colao, Annamaria / Lenzi, Andrea / Giugliano, Dario. ·Department of Cardio-Thoracic and Respiratory Sciences, Second University of Naples, Naples, Italy. ·Diabetes Care · Pubmed #23093685.

ABSTRACT: OBJECTIVE: Available evidence supports the emerging hypothesis that metabolic syndrome may be associated with the risk of some common cancers. We did a systematic review and meta-analysis to assess the association between metabolic syndrome and risk of cancer at different sites. RESEARCH DESIGN AND METHODS: We conducted an electronic search for articles published through October 2011 without restrictions and by reviewing reference lists from retrieved articles. Every included study was to report risk estimates with 95% CIs for the association between metabolic syndrome and cancer. RESULTS: We analyzed 116 datasets from 43 articles, including 38,940 cases of cancer. In cohort studies in men, the presence of metabolic syndrome was associated with liver (relative risk 1.43, P < 0.0001), colorectal (1.25, P < 0.001), and bladder cancer (1.10, P = 0.013). In cohort studies in women, the presence of metabolic syndrome was associated with endometrial (1.61, P = 0.001), pancreatic (1.58, P < 0.0001), breast postmenopausal (1.56, P = 0.017), rectal (1.52, P = 0.005), and colorectal (1.34, P = 0.006) cancers. Associations with metabolic syndrome were stronger in women than in men for pancreatic (P = 0.01) and rectal (P = 0.01) cancers. Associations were different between ethnic groups: we recorded stronger associations in Asia populations for liver cancer (P = 0.002), in European populations for colorectal cancer in women (P = 0.004), and in U.S. populations (whites) for prostate cancer (P = 0.001). CONCLUSIONS: Metabolic syndrome is associated with increased risk of common cancers; for some cancers, the risk differs betweens sexes, populations, and definitions of metabolic syndrome.

10 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.

11 Article Biliary Stone Disease in Patients with Neuroendocrine Tumors Treated with Somatostatin Analogs: A Multicenter Study. 2019

Brighi, Nicole / Panzuto, Francesco / Modica, Roberta / Gelsomino, Fabio / Albertelli, Manuela / Pusceddu, Sara / Massironi, Sara / Lamberti, Giuseppe / Rinzivillo, Maria / Faggiano, Antongiulio / Spallanzani, Andrea / Ferone, Diego / Prinzi, Natalie / Rossi, Roberta Elisa / Annibale, Bruno / Colao, Anna Maria / Campana, Davide. ·NET Team Bologna ENETS Center of Excellence, S. Orsola-Malpighi University Hospital, Alma Mater Studiorum University of Bologna, Bologna, Italy. · Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. · Digestive Disease Unit, Sant'Andrea University Hospital, ENETS Center of Excellence, Rome, Italy. · Clinical Medicine and Surgery Department - Federico II University, Naples, Italy. · Department of Oncology and Hematology, University Hospital of Modena, Modena, Italy. · Endocrinology Department (DiMi), San Martino University Hospital, Genova, Italy. · Department of Medical Oncology, Fondazione IRCCS Istituto Tumori Milano, ENETS Center of Excellence, Milan, Italy. · Gastroenterology and Endoscopy Department, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy. · Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola-Malpighi University Hospital, Bologna, Italy. · Department of Experimental Medicine, Sapienza University, Rome, Italy. · NET Team Bologna ENETS Center of Excellence, S. Orsola-Malpighi University Hospital, Alma Mater Studiorum University of Bologna, Bologna, Italy davide.campana@unibo.it. · Department of Medical and Surgical Sciences, S. Orsola-Malpighi University Hospital, Bologna, Italy. ·Oncologist · Pubmed #31694893.

ABSTRACT: BACKGROUND: Somatostatin analogs (SSAs) are the mainstay of neuroendocrine tumor (NET) treatment. Biliary stone disease is reported as a common side effect of SSAs, with a frequency ranging from 10% to 63%. Studies on SSA-treated patients for acromegaly report an increased incidence of biliary stone disease compared with the general population, whereas data on patients with NETs are few. Guidelines are based on weak evidence, thus resulting in conflicting recommendations. The aim of the study is to evaluate biliary stone disease incidence, complications, and risk factors in a large population of SSA-treated patients with NETs. MATERIALS AND METHODS: A retrospective analysis of a prospectively collected database was performed. Patients with a diagnosis of NET in seven dedicated centers from 1995 to 2017 were included at the time of SSA start. RESULTS: A total of 754 SSA-treated patients were evaluated. Patients with history of cholecystectomy or with known biliary stone disease were excluded; 478 patients were included. Among them, 118 patients (24.7%) received prophylactic ursodeoxycholic acid (UDCA). During the study period, 129 patients (27.0%) developed biliary stone disease; of them, 36 (27.9%) developed biliary complications. On multivariate analysis, primary gastrointestinal (GI)-NET (hazard ratio [HR] 1.76) and related surgery (HR 1.58) were independent risk factors for biliary stone disease. CONCLUSION: We report a high incidence of biliary stone disease particularly in GI-NET or GI surgery. UDCA prophylaxis does not seem to have a protective role. Our data suggest that all patients with primary GI-NET or undergoing abdominal surgery should be considered for prophylactic cholecystectomy; no conclusion could be drawn on the indication of prophylactic cholecystectomy in patients with primary pancreatic or thoracic NET for whom abdominal surgery is not planned. IMPLICATIONS FOR PRACTICE: The results of this study confirm an increased rate of gallstones development and related complications in patients with neuroendocrine tumors (NETs) treated with somatostatin analogs (SSAs). NETs of the gastrointestinal (GI) tract and related surgery are independent risk factors for biliary stone disease development. Therefore, all patients with primary GI-NET or undergoing abdominal surgery should be considered for prophylactic cholecystectomy. Data on other subgroups are not exhaustive, and management also evaluating additional clinical features (life expectancy, surgical and anesthesiological risks) should be considered. Prophylactic treatment with ursodeoxycholic acid does not seem to be a protective factor for SSA-related biliary stone disease.

12 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.

13 Article Heterogeneity of Duodenal Neuroendocrine Tumors: An Italian Multi-center Experience. 2018

Massironi, Sara / Campana, Davide / Partelli, Stefano / Panzuto, Francesco / Rossi, Roberta Elisa / Faggiano, Antongiulio / Brighi, Nicole / Falconi, Massimo / Rinzivillo, Maria / Delle Fave, Gianfranco / Colao, Anna Maria / Conte, Dario. ·Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy. sara.massironi@policlinico.mi.it. · Department of Medical and Surgical Sciences, Bologna University St. Orsola-Malpighi Polyclinic Hospital, Bologna, Italy. · Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, "Vita-Salute" University, Milan, Italy. · Digestive and Liver Diseases Department, University "La Sapienza" of Rome Sant'Andrea Hospital, Rome, Italy. · Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy. · Division of Endocrinology, Department of Clinical Medicine and Surgery, University "Federico II" of Naples, Naples, Italy. ·Ann Surg Oncol · Pubmed #30054824.

ABSTRACT: BACKGROUND: The optimal management of duodenal neuroendocrine neoplasms (dNENs) is unclear, and endoscopic resection is increasingly performed instead of surgery. METHODS: This is a retrospective analysis of patients with histologically confirmed diagnosis of dNENs, managed at five Italian tertiary referral Centers in Italy. RESULTS: From 2000 to 2017, 108 patients (69 males, 39 females, median age 59.5 years) were included in this study. Seventy-one patients had G1, 21 G2, 4 G3 dNENs (12 Ki-67 not available). Fifty-four patients showed metastases at diagnosis, and 20 patients developed metachronous metastases. Thirty patients had a functioning dNEN (14 metastatic). Fifty-seven patients had the dNEN surgically resected, 16 endoscopically, 23 metastatic, received medical therapy + surgery or endoscopy. Seven patients underwent liver-directed therapies, and one patient had PRRT. Median OS was 187 months. During a median follow-up of 76 months, 20 patients died (19 of disease-related causes). At Cox's multivariate proportional hazard regression, grading and age were the only variables independently related to OS. Median PFS was 170 months. Grading and staging at the initial diagnosis were independently related to PFS. No differences in terms of OS and PFS were observed between patients treated surgically or endoscopically. CONCLUSIONS: dNENs prognosis may be highly variable. These tumors can be metastatic in up to 50% of cases at the time of first diagnosis and can develop metastases thereafter. Functioning neoplasms express high metastatic potential. Nuclear imaging should be performed to exclude distant metastases in all dNENs. Endoscopy and surgery play a primary role in the management of the disease. Further prospective studies are needed.

14 Article Emerging multitarget tyrosine kinase inhibitors in the treatment of neuroendocrine neoplasms. 2018

Grillo, Federica / Florio, Tullio / Ferraù, Francesco / Kara, Elda / Fanciulli, Giuseppe / Faggiano, Antongiulio / Colao, Annamaria / Anonymous1781322. ·Pathology UnitDepartment of Surgical Sciences and Integrated Diagnostics (DISC), University of Genova, Genova, Italy federica.grillo@unige.it. · Ospedale Policlinico San Martino IRCCSGenova, Italy. · Pharmacology UnitDepartment of Internal Medicine (DIMI), University of Genova, Genova, Italy. · Department of Human Pathology of Adulthood and ChildhoodUniversity of Messina, Messina, Italy. · Unit of EndocrinologyMetabolism, Diabetology and Nutrition, Azienda Sanitaria Universitaria Integrata di Udine, Ospedale Santa Maria della Misericordia, Udine, Italy. · Neuroendocrine Tumours UnitDepartment of Clinical and Experimental Medicine, University of Sassari - AOU Sassari, Sassari, Italy. · Department of Clinical Medicine and SurgeryUniversity 'Federico II', Naples, Italy. ·Endocr Relat Cancer · Pubmed #29769293.

ABSTRACT: In the last few years, the therapeutic approach for neuroendocrine neoplasms (NENs) has changed dramatically following the approval of several novel targeted treatments. The multitarget tyrosine kinase inhibitor (MTKI), sunitinib malate, has been approved by Regulatory Agencies in pancreatic NENs. The MTKI class, however, includes several other molecules (approved for other conditions), which are currently being studied in NENs. An in-depth review on the studies published on the MTKIs in neuroendocrine tumors such as axitinib, cabozantinib, famitinib, lenvatinib, nintedanib, pazopanib, sorafenib and sulfatinib was performed. Furthermore, we extensively searched on the Clinical Trial Registries databases worldwide, in order to collect information on the ongoing clinical trials related to this topic. Our systematic analysis on emerging MTKIs in the treatment of gastroenteropancreatic and lung NENs identifies

15 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.

16 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.

17 Article Role of (68)Ga-DOTATATE PET/CT in patients with multiple endocrine neoplasia type 1 (MEN1). 2016

Lastoria, Secondo / Marciello, Francesca / Faggiano, Antongiulio / Aloj, Luigi / Caracò, Corradina / Aurilio, Michela / D'Ambrosio, Laura / Di Gennaro, Francesca / Ramundo, Valeria / Camera, Luigi / De Luca, Leonardo / Fonti, Rosa / Napolitano, Vincenzo / Colao, Annamaria. ·Division of Nuclear Medicine, Department of Diagnostic Imaging and Radiotherapy, Istituto Nazionale Tumori "Fondazione G.Pascale" - IRCCS Napoli, Naples, Italy. s.lastoria@istitutotumori.na.it. · Division of Endocrinology, Department of Clinical Medicine and Surgery, "Federico II" University of Napoli, Via Sergio Pansini 5, 80131, Naples, Italy. francescamarciello81@gmail.com. · Division of Endocrinology, Department of Clinical Medicine and Surgery, "Federico II" University of Napoli, Via Sergio Pansini 5, 80131, Naples, Italy. · Division of Nuclear Medicine, Department of Diagnostic Imaging and Radiotherapy, Istituto Nazionale Tumori "Fondazione G.Pascale" - IRCCS Napoli, Naples, Italy. · Department of Biomorphological and Functional Sciences, "Federico II" University of Napoli, Naples, Italy. · Gastrointestinal Unit, "Pellegrini Hospital", Naples, Italy. · Istitute of Biostructures and Bioimages (IBB), National Research Council, Naples, Italy. · Department of General and Specialistic Surgery, Second University of Napoli, Caserta, Italy. ·Endocrine · Pubmed #26242621.

ABSTRACT: Multiple endocrine neoplasia type 1 (MEN1) is a hereditary syndrome predisposing to many endocrine and neuroendocrine tumors (NET). Conventional imaging (CI) cannot provide satisfactory results for all the different types of MEN1-related tumors. Objective of this prospective observational study was to evaluate the role of (68)Ga-DOTATATE PET/CT in MEN1 compared to CI. Diagnostic performance of (68)Ga-DOTATATE PET/CT for the detection of NET was evaluated as well as the prognostic role of SUVmax. Eighteen patients with genetically confirmed MEN1 were evaluated by (68)Ga-DOTATATE PET/CT, endoscopic ultrasounds, multidetector-row computed tomography, magnetic resonance imaging, and hormone/markers serum measurements. Four MEN1-related tumor sites (pancreas, pituitary, parathyroids, adrenals) were considered. Sensitivity and specificity of (68)Ga-DOTATATE PET/CT for the detection of NET were calculated. There was (68)Ga-DOTATATE PET/CT uptake in 11/11 patients with pancreatic lesions, in 9/12 with pituitary adenoma, in 5/15 with parathyroid enlargements, and in 5/7 with adrenal lesions. (68)Ga-DOTATATE PET/CT showed sensitivity and specificity of 100 and 100 % in pancreas, 75 and 83 % in pituitary, 28 and 100 % in parathyroids, and 62.5 and 100 % in adrenals, respectively. Compared with CI, no significant difference in sensitivity for pancreas, pituitary, and adrenals was found, while CI had a better sensitivity for parathyroids (p = 0.002). On the ROC analysis, progression of pancreatic lesions was significantly associated to SUVmax <12.3 (p < 0.05). (68)Ga-DOTATATE PET/CT is greatly helpful in the work-up of MEN1 providing a panoramic view of MEN1-related lesions. There is also a prognostic role of (68)Ga-PET in patients with MEN1-pancreatic lesions.

18 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.

19 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.

20 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.

21 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.

22 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.

23 Article Immunohistochemical localization and quantitative expression of somatostatin receptors in normal human spleen and thymus: Implications for the in vivo visualization during somatostatin receptor scintigraphy. 2012

Ferone, D / Pivonello, R / Kwekkeboom, D J / Gatto, F / Ameri, P / Colao, A / de Krijger, R R / Minuto, F / Lamberts, S W J / van Hagen, P M / Hofland, L J. ·Department of Endocrinological and Medical Sciences and Center of Excellence for Biomedical Research, University of Genoa, Viale Benedetto XV, 6-16132-Genoa, Italy. ferone@unige.it ·J Endocrinol Invest · Pubmed #21765239.

ABSTRACT: BACKGROUND: [111In-DTPA-D-Phe1]-octreotide scintigraphy allows the visualization of SRIF receptor (SSR)-expressing tumors, including thymic tumors, and normal tissues. While the spleen is clearly visualized, the thymus is not depicted, although both contain SSR. AIM: We evaluated whether the heterogeneity, the type, and the amount of SSR might explain this contrasting finding. MATERIALS, METHODS, AND RESULTS: By ligand-binding the number of [125I-Tyr11]-SRIF- 14 binding sites resulted comparable between the two tissues, whereas the number of [125I-Tyr3]-octreotide sites was significantly higher in the spleen (p<0.001). Quantitative RTPCR showed a significantly higher expression of sst2A mRNA in the spleen, whereas a significantly higher expression of SRIF and sst3 in the thymus. The highest density of sst2A in the spleen is in line with the in vivo uptake of [111In-DTPA-D-Phe1]- octreotide, which is considered a sst2-preferring ligand. The specificity is confirmed by the evidence that in vivo [111In-DTPA- D-Phe1]-octreotide uptake can be abolished during chronic administration of "cold" octreotide. Immunohistochemistry confirmed a preferential expression of sst2A on microenvironmental cells and of sst3 on lymphoid cells. CONCLUSIONS: The heterogeneity of SSR expression and the higher SRIF content explain the lack of thymus visualization during scintigraphy, whereas thymic tumors, which do not express SRIF, are visualized. Apart from the affinity of the radioligand, also the efficacy of the internalization is crucial for the in vivo uptake, and both heterogeneity and SRIF content affect this process. These observations might have an important impact when interpretating in vivo visualization of SSR-positive lesions, and when treatment with novel SRIF analogs is considered.

24 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.

25 Article CDKN1B V109G polymorphism a new prognostic factor in sporadic medullary thyroid carcinoma. 2011

Pasquali, Daniela / Circelli, Luisa / Faggiano, Antongiulio / Pancione, Massimo / Renzullo, Andrea / Elisei, Rossella / Romei, Cristina / Accardo, Giacomo / Coppola, Viviana Raffaella / De Palma, Maurizio / Ferolla, Piero / Grimaldi, Franco / Colao, Annamaria / Colantuoni, Vittorio. ·Dipartimento Medico-Chirurgico di Internistica Clinica e Sperimentale F. Magrassi e A. Lanzara, Seconda Università di Napoli, 80131 Napoli, Italy. ·Eur J Endocrinol · Pubmed #21177330.

ABSTRACT: CONTEXT: CDKN1B encodes the cyclin-dependent kinase inhibitor p27Kip1 and is mutated in multiple endocrine neoplasia-like syndromes. CDKN1B also harbors single nucleotide polymorphisms; the T/G transversion at nucleotide 326 (the V109G variant) has been reported to be protective in breast, hereditary prostate, and pancreatic tumors. Association of CDNK1B mutations or polymorphisms with sporadic medullary thyroid carcinoma (MTC) has not been investigated yet. OBJECTIVE AND DESIGN: We screened germline DNA from 84 patients affected by sporadic MTC and 90 healthy age- and gender-matched controls for CDKN1B mutations or polymorphisms by PCR amplification and sequencing of the amplicons. We also tested all germline and 50 tumor tissue DNA for RET proto-oncogene mutations. Computed tomography, ultrasound scans, and serum calcitonin were carried out before surgery and during the follow-up and associated with CDKN1B polymorphism and disease remission. RESULTS: The T/G transversion at nucleotide 326 was the only DNA variation detected. The overall frequency of the T/G and G/G alleles in combination was 46.4%. This variant (V109G) was correlated with post-operative calcitonin levels in the normal range and biochemical remission. Conversely, the wild-type (T/T) allele was associated with post-operative calcitonin levels above normal and a higher risk to develop clinical recurrence and distant metastases. Somatic RET mutations were significantly associated with a more aggressive behavior especially in wild-type allele-bearing patients. CONCLUSIONS: Collectively, in sporadic MTC, the CDKN1B V109G polymorphism correlates with a more favorable disease progression than the wild-type allele and might be considered a new promising prognostic marker.

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