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Pancreatic Neoplasms: HELP
Articles by Sara Massironi
Based on 17 articles published since 2008

Between 2008 and 2019, Sara Massironi wrote the following 17 articles about Pancreatic Neoplasms.
+ Citations + Abstracts
1 Guideline None 2018

Grimaldi, Franco / Fazio, Nicola / Attanasio, Roberto / Frasoldati, Andrea / Papini, Enrico / Cremonini, Nadia / Davi, Maria V / Funicelli, Luigi / Massironi, Sara / Spada, Francesca / Toscano, Vincenzo / Versari, Annibale / Zini, Michele / Falconi, Massimo / Oberg, Kjell. ·Endocrinology and Metabolic Disease Unit, Azienda Sanitaria Universitaria Integrata di Udine, Udine, Italy. · Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumor, European Institute of Oncology, Milan, Italy. · Endocrinology Service, Galeazzi Institute IRCCS, Milan, Italy. · Endocrinology Unit, Azienda Ospedaliera S. Maria Nuova IRCCS, Reggio Emilia, Italy. · Department of Endocrinology and Metabolic Diseases, Regina Apostolorum Hospital, Albano Laziale (Rome), Italy. · Endocrinology Clinics, Clinica Villalba, Bologna, Italy. · Section of Endocrinology, Medicina Generale e Malattie Aterotrombotiche e Degenerative, Azienda Ospedaliera Universitaria Integrata, Verona, Italy. · Division of Radiology, European Institute of Oncology, Milan, Italy. · Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy. · Endocrinology, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy. · Nuclear Medicine Unit, Azienda Ospedaliera S. Maria Nuova IRCCS, Reggio Emilia, Italy. · Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Vita e Salute University, Milan, Italy. · Department of Endocrine Oncology, University Hospital, Uppsala, Sweden. ·Endocr Metab Immune Disord Drug Targets · Pubmed #29237387.

ABSTRACT: Well-established criteria for evaluating the response to treatment and the appropriate followup of individual patients are critical in clinical oncology. The current evidence-based data on these issues in terms of the management of gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN) are unfortunately limited. This document by the Italian Association of Clinical Endocrinologists (AME) on the criteria for the follow-up of GEP-NEN patients is aimed at providing comprehensive recommendations for everyday clinical practice based on both the best available evidence and the combined opinion of an interdisciplinary panel of experts. The initial risk stratification of patients with NENs should be performed according to the grading, staging and functional status of the neoplasm and the presence of an inherited syndrome. The evaluation of response to the initial treatment, and to the subsequent therapies for disease progression or recurrence, should be based on a cost-effective, risk-effective and timely use of the appropriate diagnostic resources. A multidisciplinary evaluation of the response to the treatment is strongly recommended and, at every step in the follow-up, it is mandatory to assess the disease state and the patient performance status, comorbidities, and recent clinical evolution. Local expertise, available technical resources and the patient preferences should always be evaluated while planning the individual clinical management of GEP-NENs.

2 Review Duodenal neuroendocrine neoplasms: a still poorly recognized clinical entity. 2018

Rossi, Roberta Elisa / Rausa, Emanuele / Cavalcoli, Federica / Conte, Dario / Massironi, Sara. ·a Department of Gastroenterology and Endoscopy , Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico , Milan , Italy. · b Department of Pathophysiology and Organ Transplant , Università degli Studi di Milano , Milan , Italy. · c General and Emergency Surgery Department , ASST Trauma Center "Papa Giovanni XXIII" Hospital , Bergamo , Italy. ·Scand J Gastroenterol · Pubmed #29726295.

ABSTRACT: BACKGROUND: Duodenal neuroendocrine neoplasms (dNENs) are rare tumors, which usually show good prognosis. The optimal management of these tumors is still far from being clearly understood because of their rarity and the poor level of knowledge about their natural history. Herein, we have reviewed the literature on dNENs to collect and analyze the current data on epidemiology, diagnosis and management of these rare tumors. METHODS: Bibliographical searches were performed in PubMed, using the following keywords: duodenal neuroendocrine neoplasm; duodenum; gastrinoma; diagnosis; therapy; guidelines. We searched for all relevant articles published over the last 15 years. Non-English language papers were excluded. RESULTS: We reviewed the pertinent articles about dNENs. Upper gastrointestinal endoscopy with biopsy is the cornerstone of the dNENs diagnostic process. Endoscopic ultrasound with fine-needle aspiration/biopsy should be performed in order to locally stage the disease and in all cases of non-diagnostic endoscopy. Endoscopic or complete surgical removal of the primary lesion is the recommended treatment and is generally achievable for the majority of the patients. A less aggressive approach may be suggested for well-differentiated low-stage tumors. After NEN removal, patients should be closely followed-up especially during the first 3 years by endoscopic examination, imaging tests and CgA measurements. CONCLUSIONS: The multi-disciplinary approach and the preservation of the quality of life of the patients play a key role in the therapeutic process for dNENs. Further studies are needed to better define standardized guidelines specific to dNENs, including optimal management approaches and follow-up intervals.

3 Review Somatostatin analogues in functioning gastroenteropancreatic neuroendocrine tumours: literature review, clinical recommendations and schedules. 2016

Massironi, Sara / Conte, Dario / Rossi, Roberta Elisa. ·a Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico , Milan , Italy ; · b Department of Pathophysiology and Transplantation , Università Degli Studi Di Milano , Milan , Italy. ·Scand J Gastroenterol · Pubmed #26605828.

ABSTRACT: OBJECTIVE: Neuroendocrine tumours (NETs) represent a heterogeneous group of neoplasms, which include functioning and non-functioning forms. Somatostatin analogues (SSAs) play a key role in the management of these tumours. Herein, we aimed at reviewing the current evidence about the role of SSAs in the treatment of gastro-entero-pancreatic (GEP)-NETs. MATERIAL AND METHODS: An extensive bibliographical search was performed in PubMed using the following keywords: gastro-entero-pancreatic neuroendocrine tumours, somatostatin analogues, octreotide, lanreotide, in order to identify all the pertinent English-written articles published between 1990 and 2015. RESULTS: SSAs have shown to help the symptomatic and biochemical improvement of patients with NETs and to exhibit a good safety profile. Recent studies have also reported a role for SSAs in tumour growth control, although the results are less impressive and the underlying mechanisms are not fully understood. CONCLUSIONS: SSAs are well known as a symptomatic and, to lesser extent, anti-proliferative treatment in GEP-NETs. However, some issues, including optimal dosage, benefits and adverse events of combination with other molecules, and the role of new analogues, remain to be elucidated in further randomised studies.

4 Review An esophageal gastrointestinal stromal tumor in a patient with MEN1-related pancreatic gastrinoma: an unusual association and review of the literature. 2014

Massironi, Sara / Rossi, Roberta E / Ferrero, Stefano / Cavalcoli, Federica / Spampatti, Matilde P / Conte, Dario / Corbetta, Sabrina / Peracchi, Maddalena. ·Gastroenterology and Endoscopy Unit, Department of Pathophysiology and Transplant, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Italy. ·J Cancer Res Ther · Pubmed #25022420.

ABSTRACT: Both multiple endocrine neoplasia type 1 (MEN1)-related gastrinomas and gastrointestinal stromal tumors (GISTs) are rare neoplasms, and their association has been rarely reported. We describe an unusual association between a GIST and a MEN1-related gastrinoma. A 44-year-old man had undergone surgical removal of a pancreatic gastrinoma in 2004 and was then administered long-term somatostatin analogs, and diagnosed as having MEN1 syndrome. Following an uneventful follow-up, in April 2009, an upper gastrointestinal tract endoscopy showed esophageal narrowing, with evidence of a 2-cm solid mass on endoscopic ultrasonography. Histology revealed a tumor composed of elongated cells with plump cytoplasm arranged in a storiform pattern. The immunophenotype of the lesion was CD117 and Platelet Derived Growth Factor (PDGF) positive, whereas alpha-1 muscle actin and S-100 protein were negative. Due to morphological and immunohistochemical results, a final diagnosis of esophageal GIST was made. The association between GISTs and MEN1 could be casual, although a single case of the coexistence of a GIST and a MEN1-related gastrinoma has already been reported. A role of the MEN1 gene in the pathogenesis of GISTs could be hypothesized.

5 Review Gastrinoma and neurofibromatosis type 2: the first case report and review of the literature. 2014

Massironi, Sara / Zilli, Alessandra / Rossi, Roberta Elisa / Cavalcoli, Federica / Conte, Dario / Peracchi, Maddalena. ·Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Università degli Studi di Milano, Via F, Sforza 35, Milano 20122, Italy. sara.massironi@policlinico.mi.it. ·BMC Gastroenterol · Pubmed #24961548.

ABSTRACT: BACKGROUND: Gastroenteropancreatic neuroendocrine tumors have occasionally been described in association with neurofibromatosis type 1, whereas an association with neurofibromatosis type 2 has never been reported. CASE PRESENTATION: This report refers to an Italian 69 year old woman with neurofibromatosis type 2 and a pancreatic gastrinoma. In the past she had encephalic meningiomas, a tongue schwannoma and bilateral acoustic neurinomas. She presented with weight loss and a long-term history of diarrhea, responsive to proton pump inhibitors. Upper gastrointestinal endoscopy revealed peptic ulcer of the duodenal bulb. Blood tests were normal, except for the elevation of plasma gastrin (1031 pg/ml; reference value <108) and chromogranin A (337 U/L; reference value <36). After secretin stimulation testing, the plasma gastrin level rose to 3789 pg/ml. The abdomen magnetic resonance imaging and gallium68-DOTATOC positron emission tomography scan demonstrated the presence of a 1.2 x 2 cm lesion in the pancreatic head and a liver metastatis. Pancreatic endoscopic ultrasound with fine needle aspiration revealed cytomorphologic features suggestive of pancreatic gastrinoma. Brain magnetic resonance showed a pituitary microadenoma. There was no evidence of hyperparathyroidism. The genetic test for multiple endocrine neoplasia type 1 syndrome mutation was negative. CONCLUSION: This report focuses on the first case of coexistence of gastrinoma with neurofibromatosis type 2. Although the clinical relevance of this association remains to be determined, our case report will surely give cause for due consideration.

6 Review Neuroendocrine tumors of the gastro-entero-pancreatic system. 2008

Massironi, Sara / Sciola, Valentina / Peracchi, Maddalena / Ciafardini, Clorinda / Spampatti, Matilde Pia / Conte, Dario. ·Gastroenterology Unit II, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Via Sforza 35, Milan, Italy. ·World J Gastroenterol · Pubmed #18803349.

ABSTRACT: Gastro-entero-pancreatic (GEP) neuroendocrine tumors (NETs) are rare neoplasms, although their prevalence has increased substantially over the past three decades. Moreover, there has been an increased clinical recognition and characterization of these neoplasms. They show extremely variable biological behavior and clinical course. Most NETs have endocrine function and secrete peptides and neuroamines that cause distinct clinical syndromes, including carcinoid syndrome; however, many are clinically silent until late presentation with mass effects. Investigation and management should be individualized for each patient, taking into account the likely natural history of the tumor and general health of the patient. Management strategies include surgery for cure or palliation, and a variety of other cytoreductive techniques, and medical treatment including chemotherapy, and biotherapy to control symptoms due to hormone release and tumor growth, with somatostatin analogues (SSAs) and alpha-interferon. New biological agents and somatostatin-tagged radionuclides are under investigation. Advances in the therapy and development of centers of excellence which coordinate multicenter studies, are needed to improve diagnosis, treatment and therefore survival of patients with GEP NETs.

7 Article Chromogranin A in the Follow-up of Gastroenteropancreatic Neuroendocrine Neoplasms: Is It Really Game Over? A Systematic Review and Meta-analysis. 2018

Rossi, Roberta Elisa / Ciafardini, Clorinda / Sciola, Valentina / Conte, Dario / Massironi, Sara. ·From the Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Department of Pathofisiology and Transplantation, Università degli Studi di Milano, Milan, Italy. ·Pancreas · Pubmed #30325865.

ABSTRACT: OBJECTIVES: Little is known about chromogranin A (CgA) during follow-up of gastroenteropancreatic neuroendocrine neoplasms. We hypothesized that serial CgA monitoring might be useful for the assessment of tumor progression, and we performed a systematic review of the literature and meta-analysis. METHODS: A bibliographical search was performed in PubMed using "chromogranin A" and "neuroendocrine tumors" and "follow-up" and "biomarker" to identify all pertinent articles published in the last 10 years. RESULTS: Eight studies were included in current meta-analysis. Chromogranin A as a follow-up marker shows sensitivity between 46% and 100% and specificity between 68% and 90%. The meta-analysis results showed an overall accuracy of 84% (95% confidence interval [CI], 81-86.6), a cumulative sensitivity of 74.6% (95% CI, 61.9-85.4), and a cumulative specificity of 84.7% (95% CI, 81.3-87.7). These data indicate that circulating CgA has a better overall accuracy in the follow-up setting; it can be used to rule the diagnosis of recurrence/progression in, rather than to rule it out. CONCLUSIONS: Chromogranin A is more reliable when used to monitor disease progression and response to treatment and for the early detection of recurrence after treatment rather than in the diagnostic setting. It is more sensible to use this marker in those cases where the initial values were impaired.

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

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

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

9 Article Vasostatin-1: A novel circulating biomarker for ileal and pancreatic neuroendocrine neoplasms. 2018

Corsello, Andrea / Di Filippo, Luigi / Massironi, Sara / Sileo, Federica / Dolcetta Capuzzo, Anna / Gemma, Marco / Carlucci, Claudia / Cusini, Claudio / Colombo, Barbara / Dallatomasina, Alice / Franchi, Giulia Maria / Corti, Angelo / Manzoni, Marco Federico. ·Department of General Medicine and Endocrine Tumor Unit, San Raffaele Scientific Institute, Milan, Italy. · Department of Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. · Department of Neurointensive Care, San Raffaele Scientific Institute, Milan, Italy. · Clinical study & Data Management Unit, Haematology Project Foundation, Vicenza, Italy. · Division of Experimental Oncology, San Raffaele Scientific Institute, Milan, Italy. · San Raffaele Vita-Salute University, Milan, Italy. ·PLoS One · Pubmed #29723285.

ABSTRACT: BACKGROUND: Chromogranin A (CgA) is a plasma biomarker widely used in the follow-up of patients with neuroendocrine neoplasms (NENs). However, its accuracy as a tumor biomarker is relatively low because plasma CgA can increase also in patients with other diseases or in subjects treated with proton-pump inhibitors (PPIs), a class of widely-used drugs. METHODS: In the attempt to identify a more reliable biomarker for NENs, we investigated, by ELISA, the circulating levels of full-length CgA (CgA1-439) and of various CgA-derived fragments in 17 patients with ileal or pancreatic NENs, 10 healthy controls, and 21 healthy volunteers before and after treatment with PPIs. RESULTS: Patients with ileal or pancreatic NENs showed increased plasma levels of total-CgA and CgA1-76 fragment (vasostatin-1, VS-1) compared to controls [median (25th-75th-percentiles); total-CgA: 1.85 nM (1.01-4.28) vs 0.75 nM (0.52-0.89), p = 0.004; VS-1: 2.76 nM (1.09-7.10) vs 0.29 nM (0.26-0.32), p<0.001, respectively], but not of CgA1-439 or CgA1-373 fragment. VS-1 positively correlated with total-CgA (r = 0.65, p<0.001). The Receiver Operating Characteristic area under the curve was 0.9935 for VS-1 and 0.8824 for total-CgA (p = 0.067). Treatment of patients with somatostatin analogues decreased both total-CgA and VS-1. In contrast, administration of PPIs increased the plasma levels of total-CgA, but not of VS-1. CONCLUSION: These findings suggest that plasma VS-1 is a novel biomarker for ileal and pancreatic NENs. Considering that VS-1 is a well-defined fragment not induced by proton-pump inhibitors, this polypeptide might represent a biomarker for NENs diagnosis and follow-up more accurate and easier to standardize than CgA.

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

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

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

11 Article A case of positive 2018

Zilli, Alessandra / Fanetti, Ilaria / Conte, Dario / Massironi, Sara. ·Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milan, Italy; Postgraduate School of Gastroenterology, Università degli Studi di Milano, Milan, Italy. · Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milan, Italy. Electronic address: sara.massironi@policlinico.mi.it. ·Clin Imaging · Pubmed #29529451.

ABSTRACT: Gallium-68 DOTA-peptide positron emission tomography/computed tomography (

12 Article Impact of Vitamin D on the Clinical Outcome of Gastro-Entero-Pancreatic Neuroendocrine Neoplasms: Report on a Series from a Single Institute. 2017

Massironi, Sara / Zilli, Alessandra / Bernasconi, Susanna / Fanetti, Ilaria / Cavalcoli, Federica / Ciafardini, Clorinda / Felicetta, Irene / Conte, Dario. ·Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. ·Neuroendocrinology · Pubmed #28122374.

ABSTRACT: BACKGROUND/AIMS: Vitamin D deficiency is hypothesized to represent a risk factor in several neoplasms. The aim of this study was to determine whether serum 25-hydroxyvitamin D (25-OHvitD) deficiency represents a risk factor for neuroendocrine neoplasms (NENs) and can be associated with overall survival (OS) and progression-free survival (PFS). METHODS: From 2010 to 2015, 138 patients with gastro- entero-pancreatic NENs (61 females; median age, 63 years) were included in the study. Serum 25-OHvitD levels, which were measured at baseline, were defined as deficient if ≤20 ng/mL. In such cases, 25-OHvitD supplementation was administered to the patients. The possible associations between 25-OHvitD levels and disease grading, staging, overall OS, and PFS were considered. Furthermore, the possible association between 25-OHvitD supplementation and PFS or OS was evaluated by Cox proportional hazards regression. RESULTS: Median 25-OHvitD levels were 12.9 ng/mL (range 2-32); in detail, 94 patients (68%) had ≤20 ng/mL, with 46 cases (33%) having ≤10 ng/mL. An inverse correlation was observed between 25-OHvitD levels and OS (p = 0.03, rs = -0.18) and PFS (p = 0.01, rs = -0.22). At Cox proportional hazards regression, mortality was not related to 25-OHvitD levels; however, there was an association between 25-OHvitD supplementation and OS (p < 0.002). CONCLUSIONS: Vitamin D deficiency is highly prevalent among NEN patients. 25-OHvitD supplementation potentially plays an important role in the correction of 25-OHvitD values, and has an influence on the clinical outcome. However, further studies are needed to confirm this observation.

13 Article A wait-and-watch approach to small pancreatic neuroendocrine tumors: prognosis and survival. 2016

Massironi, Sara / Rossi, Roberta Elisa / Zilli, Alessandra / Casazza, Giovanni / Ciafardini, Clorinda / Conte, Dario. ·Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. · Postgraduate School of Gastroenterology, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy. · Department of Biomedical and Clinical Sciences "L. Sacco", University of Milan, Milan, Italy. ·Oncotarget · Pubmed #26959887.

ABSTRACT: BACKGROUND: Whether all the small (ø≤20mm) non-functional pancreatic neuroendocrine neoplasms (pNENs) should be routinely resected is unclear. AIM: To assess the overall survival (OS) and progression-free survival (PFS) of patients with small pNENs, followed-up with different management options. MATERIAL AND METHODS: Between 2007-2014, 51 patients were newly diagnosed with pNEN. 15 patients with pNENs ø ≤20 mm underwent an intensive follow-up at 3-month intervals during the first year and then every 6 months (FU pNEN group). They were all at TNM stage I, except for one patient at stage IIA. 21 patients underwent surgical resection (SR pNEN group): 2 patients were at TNM stage I, 9 IIA, one IIIB, 9 IV. 15 patients received systemic therapy (ST pNEN group) due to advanced disease or contraindications to surgery: 5 were at stage IIA, 2 IIB, 8 IV. RESULTS: The median follow-up for the entire cohort was 50 months. Survival was similar in the FU and SR pNEN groups, but significantly worst in the ST pNEN patients (log-rank test P <0.05). The 4-year survival rate was 100% in the FU pNEN group, 90.5% among the SR pNEN patients, 61% for the ST pNEN ones (p <0.0001). The disease remained stable in all but one patient in the FU pNEN group, whereas six patients in the SR group and five in the ST group showed disease progression. CONCLUSIONS: The "wait-and-watch" approach to early-stage small pNENs appears to be safe although further studies are needed to confirm these results in larger cohorts of patients.

14 Article Sunitinib-induced complete response in metastatic renal cancer expressing neuroendocrine markers: a new predictive factor? 2014

Gambini, Donatella / Locatelli, Elisa / Gianelli, Umberto / Bareggi, Claudia / Galassi, Barbara / Visintin, Roberto / Massironi, Sara / Dell'orto, Paolo G / Tomirotti, Maurizio. ·Unit of Medical Oncology, IRCCS Ca' Granda - Maggiore Policlinico Hospital Foundation, Milan, Italy gambini.donatella@policlinico.mi.it. · Unit of Medical Oncology, IRCCS Ca' Granda - Maggiore Policlinico Hospital Foundation, Milan, Italy. · Hematopathology Section, Pathology Unit, Department of Pathophysiology and Transplantation, University of Milan School of Medicine, Milan, Italy. · Unit of Gastroenterology and Endoscopy, IRCCS Ca' Granda - Maggiore Policlinico Hospital Foundation, Milan, Italy. · Urology Unit, Clinical Surgery I, University Milan School of Medicine, IRCCS Ca' Granda - Maggiore Policlinico Hospital Foundation, Milan, Italy. ·Anticancer Res · Pubmed #25503173.

ABSTRACT: BACKGROUND: To date, no predictive factors are recognized and applied in the therapeutic choice for metastatic renal cell carcinoma. Due to significant side-effects and costs, which are relevant issues in this setting, optimization of treatments has become a priority. CASE REPORT: We herein report a case of complete remission of metastatic renal cell carcinoma after 1 year of treatment with sunitinib. Since pancreatic metastases were detected by a 68Ga-DOTA-NOC positron emission tomography, it was decided to perform a histological revision of the specimens, with immunohistochemical staining for neuroendocrine markers on the primary tumor. CONCLUSION: On the basis of the detection of neuroendocrine markers on the primary neoplasm, together with pancreatic metastases positive on a 68Ga-DOTA-NOC positron emission tomography (PET), we hypothesize and discuss about a potential role of specific neuroendocrine markers as predictive indicators of response to sunitinib (and allegedly to other target therapies) in the treatment of this neoplasm.

15 Article Chromogranin A in diagnosing and monitoring patients with gastroenteropancreatic neuroendocrine neoplasms: a large series from a single institution. 2014

Massironi, Sara / Rossi, Roberta Elisa / Casazza, Giovanni / Conte, Dario / Ciafardini, Clorinda / Galeazzi, Marianna / Peracchi, Maddalena. ·Division of Gastroenterology and Digestive Endoscopy, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. ·Neuroendocrinology · Pubmed #25428270.

ABSTRACT: BACKGROUND/AIMS: Plasma chromogranin A (CgA) is the most widely used biochemical biomarker in the diagnostic workup and follow-up of gastroenteropancreatic neuroendo- crine neoplasms (GEP-NENs). Herein, we assessed the clinical utility of CgA in diagnosing and monitoring a large series of GEP-NENs. PATIENTS AND METHODS: A total of 181 GEP-NEN patients (87 males, 94 females) with pancreatic (n = 81) and gastrointestinal neoplasms (n = 100) were included; 99 patients had grade (G)1 NENs (Ki-67 ≤2%), 57 G2 NENs (Ki-67 3-20%) and 25 G3 NENs (Ki-67 >20%); 81 patients had tumor-node-metastasis (TNM) stage I, 14 stage II, 17 stage III and 69 stage IV cancer. For every patient, CgA values were assessed at diagnosis and during follow-up. RESULTS: At diagnosis, the CgA values were above the upper reference limit in 148 patients (82%); the median CgA levels were significantly higher in functioning than in nonfunctioning tumors (295 vs. 43 U/l; p = 0.0001) as well as significantly higher in patients with metastases than in those without metastases (324.5 vs. 42 U/l; p = 0.0001). In logistic regression analysis, baseline CgA levels were significantly associated with Ki-67 index (p < 0.0001) and TNM stage (p < 0.0001) independently of the age and sex of the patient and the primary site of the tumor. The overall 5- and 10-year survival rates were 74 and 64.5%, respectively. A low Ki-67 index, the type of treatment and an early CgA decrease after treatment were positively correlated with the survival rate. After radical surgery, 15/95 patients relapsed, and an increase in CgA values anticipated the clinical and objective disease recurrence after a period of 9-12 months. CONCLUSIONS: In GEP-NENs, plasma CgA has a significant prognostic relevance.

16 Article Plasma chromogranin A response to octreotide test: prognostic value for clinical outcome in endocrine digestive tumors. 2010

Massironi, Sara / Conte, Dario / Sciola, Valentina / Spampatti, Matilde Pia / Ciafardini, Clorinda / Valenti, Luca / Rossi, Roberta Elisa / Peracchi, Maddalena. ·Gastroenterology Unit II, Fondazione IRCCS Policlinico, Mangiagalli e Regina Elena, Milan, Italy. sara.massironi@libero.it ·Am J Gastroenterol · Pubmed #20372113.

ABSTRACT: OBJECTIVES: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) expressing somatostatin receptors may be treated with somatostatin analogs (SSAs). Selection criteria are a positive Octreoscan or a >50% hormone level decrease after octreotide subcutaneous (s.c.) injection (octreotide test) (OT). Plasma chromogranin A (CgA) is the best general GEP-NET marker, but data on CgA response to OT are scanty. Thus, we evaluated whether plasma CgA response to OT could predict the clinical response to SSAs. METHODS: At diagnosis, 38 GEP-NET patients received octreotide 200 microg s.c., with plasma CgA determination at 0, 3, and 6 h. Long-term SSA treatment was then given by monitoring symptomatic, biochemical, and objective responses, and survival. RESULTS: Basal plasma CgA levels were significantly higher in patients with functioning than non-functioning tumors (median (range): 220 (18-2,230) vs. 46 (25-8,610) U/l, P=0.03) and in those with than without metastases (171 (18-8,610) vs. 43 (28-220) U/l, P=0.04). CgA levels significantly correlated with WHO classification, clinical TNM staging, and Ki-67 proliferative index. After OT, CgA levels decreased from 146 (18-8,610) to 61 (10-8,535) U/l (basal and nadir values), P<0.001. In patients responsive to OT, a successful objective response occurred in 21/31 patients (68%). Successful symptomatic response occurred in 13/18 patients (72%), biochemical response in 25/31 (81%), and objective response in 21/31 (68%). In the remaining seven unresponsive cases, with CgA decrement <30%, disease progressed to death in six (86%). Median survival from enrollment was 48 months (6-138) in responsive and 6 (6-30) in unresponsive patients (P=0.0005). CONCLUSIONS: In GEP-NETs, plasma CgA is a reliable marker, and a >30% decrease after OT has a relevant prognostic meaning allowing the identification of the subgroup of patients most likely to be responsive to chronic SSAs.

17 Article Contrast-enhanced ultrasonography in evaluating hepatic metastases from neuroendocrine tumours. 2010

Massironi, Sara / Conte, Dario / Sciola, Valentina / Pirola, Lorena / Paggi, Silvia / Fraquelli, Mirella / Ciafardini, Clorinda / Spampatti, Matilde P / Peracchi, Maddalena. ·Gastroenterology Unit II, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Via F Sforza 35, 20122 Milano, Italy. sara.massironi@libero.it ·Dig Liver Dis · Pubmed #20172770.

ABSTRACT: OBJECTIVES: At presentation, gastroenteropancreatic neuroendocrine tumours (GEP NETs) frequently show prognostically negative hepatic involvement. The aim of this study was to characterise hepatic metastases of GEP NETs as revealed by contrast-enhanced ultrasonography (CEUS), which allows the fine definition of the microvascular system, and to correlate these findings to the biological behaviour of the tumour. METHODS: Eighteen out of 62 GEP NET patients examined between January 2007 and September 2008 had histologically proven hepatic metastases from primary ileal (#6), gastric (#1) or rectal (#1) carcinoids, pancreatic tumours (#7), or primary duodenal (#2) or occult gastrinomas (#1), and all underwent low mechanical index real-time CEUS with SonoVue injection. RESULTS: Strong early enhancement in the arterial phase was observed in 15 cases (83%), and a rapid wash-out in the portal venous phase in 14 (78%). In the late venous phase, the lesions were hypoechoic in 12 cases (67%), isoechoic in five (28%), and hyperechoic in one (0.05%). The time of arterial enhancement correlated with the Ki-67 proliferative index (r(s)=0.516; p=0.028). CONCLUSIONS: Most of the neuroendocrine liver metastases showed increased arterial enhancement at CEUS, a behaviour that is similar to that of hepatocellular carcinomas and the opposite of that of other metastases. CEUS can be a useful diagnostic means of characterising such metastases.