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Pancreatic Neoplasms: HELP
Articles by Davide Campana
Based on 28 articles published since 2008
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Between 2008 and 2019, D. Campana wrote the following 28 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Review Sporadic Small (≤20 mm) Nonfunctioning Pancreatic Neuroendocrine Neoplasm: is the Risk of Malignancy Negligible When Adopting a More Conservative Strategy? A Systematic Review and Meta-analysis. 2017

Ricci, Claudio / Casadei, Riccardo / Taffurelli, Giovanni / Pacilio, Carlo Alberto / Campana, Davide / Ambrosini, Valentina / Donatella, Santini / Minni, Francesco. ·Department of Internal Medicine and Surgery (DIMEC), Chirurgia Generale-Minni, Alma Mater Studiorum-Università di Bologna, Bologna, Italy. claudio.ricci6@unibo.it. · Department of Internal Medicine and Surgery (DIMEC), Chirurgia Generale-Minni, Alma Mater Studiorum-Università di Bologna, Bologna, Italy. · Department of Specialized Diagnostic and Experimental Medicine (DIMES), Bologna, Italy. ·Ann Surg Oncol · Pubmed #28681158.

ABSTRACT: BACKGROUND: The management of small (≤20 mm), nonfunctioning pancreatic neuroendocrine neoplasms (pNENs) remains under debate. The European Neuroendocrine Tumor Society guidelines advocate the possibility of a conservative approach. METHODS: A systematic literature search was conducted to identify all studies comparing the risk of malignancy in small pNENs with respect to large ones (>20 mm). Malignancy was defined based on the presence of nodal metastases. Distant metastases, tumor grading (G2-3), vascular microscopic invasion, stage III-IV, and overall and disease-free survival also were evaluated. The data were reported in two ways: using the risk difference (RD) and the likelihood of being helped or harmed (LHH). RESULTS: The search identified only 6 eligible studies with an overall population of 1697 resected pNENs: 382 (22.5%) small and 1315 (77.5%) large. The RD of lymph nodal metastases was -0.26 (95% confidence interval (CI): -0.31 to -0.22; P < 0.001). The LHH was 0.34, suggesting that the risk of leaving a malignancy during follow-up due to the adoption of a conservative strategy was three times higher than the benefits. The risk difference of distant metastases, G3 lesions, G2-G3 lesions, stage III/IV, microscopic vascular invasion, death, and recurrence of the disease were lower in small NF-PNETs than large ones. The related LHH values suggested that a watch-and-wait policy never provided a benefit. CONCLUSIONS: Even if the malignancy rate in sporadic, small pancreatic neuroendocrine neoplasms was lower than in large ones, this difference did not justify a watch-and-wait policy.

2 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.

3 Clinical Trial Pancreatic endocrine tumors less than 4 cm in diameter: resect or enucleate? a single-center experience. 2010

Casadei, Riccardo / Ricci, Claudio / Rega, Daniela / D'Ambra, Marielda / Pezzilli, Raffaele / Tomassetti, Paola / Campana, Davide / Nori, Francesca / Minni, Francesco. ·Dipartimento di Scienze Chirurgiche e Anestesiologiche, Policlinico S. Orsola-Malpighi, Alma Mater Studiorum Università di Bologna, Bologna, Italy. riccardo.casadei@aosp.bo.it ·Pancreas · Pubmed #20431423.

ABSTRACT: OBJECTIVE: Pancreatic endocrine tumors (PETs) are usually small, benign or low-grade malignant, and surgery should preserve the pancreatic parenchyma as much as possible. The aim of the study was to evaluate the postoperative and long-term survival of patients undergoing enucleation in small PETs. METHODS: Of 82 patients having PETs, 46 with tumor less than 4 cm in diameter, without distant metastases and with R0 resection by final pathologic examination, were included in this study. Enucleation was performed when the tumor did not involve the main pancreatic duct and in the absence of peripancreatic lymphadenopathy (group A); a typical resection was carried out in all other cases (group B). The 2 groups were compared regarding postoperative mortality and morbidity, pancreatic fistula, postoperative hospital stay, reoperation, World Health Organization classification, TNM stage, recurrence, and long-term survival. RESULTS: There were 15 patients (32.6%) in group A and 31 (67.4%) in group B. Postoperative and long-term results were similar in the 2 groups, whereas World Health Organization classification was significantly different; enucleation was performed more frequently than typical R0 resection in benign tumors (P = 0.009). CONCLUSIONS: Enucleation should be reserved for patients having benign PETs less than 4 cm in diameter and far from the main pancreatic duct.

4 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.

5 Article Is radical surgery always curative in pancreatic neuroendocrine tumors? A cure model survival analysis. 2018

Ricci, Claudio / Casadei, Riccardo / Taffurelli, Giovanni / Campana, Davide / Ambrosini, Valentina / Pacilio, Carlo Alberto / Santini, Donatella / Brighi, Nicole / Minni, Francesco. ·Department of Internal Medicine and Surgery (DIMEC), Italy. Electronic address: claudiochir@gmail.com. · Department of Internal Medicine and Surgery (DIMEC), Italy. · Department of Haematology and Oncology (DIMES), Alma Mater Studiorum, University of Bologna, S.Orsola-Malpighi Hospital, Italy. ·Pancreatology · Pubmed #29487026.

ABSTRACT: BACKGROUND: Adjuvant therapy after curative surgery for sporadic pancreatic neuroendocrine tumor (pNETs) is not currently recommended, assuming that all patients could be cured by a radical resection. The aim of our study is to establish how many and which kind of patients remained uncured after radical resection of pNET. METHODS: Retrospective study involving 143 resected sporadic pNETs. The survival analysis was carried out using the cure model, describing the cure fraction and the excess of risk recurrence. Multivariate analyses were made in order to evaluate the non negligible effect of demographics, clinical and pathological factors on survival parameters. The results were reported as percentages, fractions, ORs and HRs with 95% confidence interval (95 CI %). RESULTS: The cure fraction and the excess of hazard rate of the whole population were 57.1% (37.4-74.6, 95% CI) and 0.06 (0.03-0.07, 95% CI), respectively. Two independent factors were related to the cure fraction: TNM stage (OR 0.27 ± 0.17; P = 0.002) and grading (OR 0.11 ± 0.18; P = 0.004). Considering the excess of hazard rate, only two independent factors were related to an increased risk of recurrence: TNM stage (HR 3.49 ± 1.12; P = 0.004) and grading (HR 4.93 ± 1.82; P < 0.001). CONCLUSION: The radical surgery has a high probability of cure in stages I-II or in grading 1 while, in stages III-IV or in grading 3 tumors, surgery alone failed to achieve a "cure". A multimodal treatment should be employed in order to avoid a recurrence of the disease.

6 Article Sunitinib in patients with pre-treated pancreatic neuroendocrine tumors: A real-world study. 2018

Rinzivillo, Maria / Fazio, Nicola / Pusceddu, Sara / Spallanzani, Andrea / Ibrahim, Toni / Campana, Davide / Marconcini, Riccardo / Partelli, Stefano / Badalamenti, Giuseppe / Brizzi, Maria Pia / Catena, Laura / Schinzari, Giovanni / Carnaghi, Carlo / Berardi, Rossana / Faggiano, Antongiulio / Antonuzzo, Lorenzo / Spada, Francesca / Gritti, Sara / Femia, Daniela / Gelsomino, Fabio / Bongiovanni, Alberto / Ricci, Sergio / Brighi, Nicole / Falconi, Massimo / Delle Fave, Gianfranco / Panzuto, Francesco. ·Digestive and Liver Disease, ENETS Center of Excellence Sant'Andrea Hospital - Sapienza University of Rome, Italy. · Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, ENETS Center of Excellence IEO, Milan, Italy. · Department of Medical Oncology, Fondazione IRCCS Istituto Tumori Milano, ENETS Center of Excellence, Milan, Italy. · Division of Oncology, Department of Oncology and Haematology, University Hospital of Modena, Modena, Italy. · Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. · Department of Medical and Surgical Sciences, S.Orsola-Malpighi University Hospital, Bologna, Italy. · Department of Oncology, Azienda Ospedaliero-Universitaria Pisana and University of Pisa, Istituto Toscano Tumori, Santa Chiara Hospital, Pisa, Italy. · Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Vita e Salute University, Milan, Italy. · Department of Surgical and Oncological Sciences, University of Palermo, Palermo, Italy. · Medical Oncology, AOU S. Luigi Gonzaga Regione Gonzole 10, Orbassano, Italy. · Struttura di Oncologia Policlinico di Monza, Monza, MB, Italy. · Medical Oncology, Università Cattolica del Sacro Cuore, Rome, Italy. · Oncology Unit, Humanitas Clinical and Research Centre, Rozzano, Italy. · Medical Oncology, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I, Ancona, Italy. · Divisione di Endocrinologia, Dipartimento di Medicina Clinica e Chirurgia, Università di Napoli Federico II, ENETS Center of Excellence Naples, Italy. · S.C di Oncologia Medica, AOU Careggi Florence, Italy. · Department of Experimental, Diagnostic and Specialty Medicine, S.Orsola-Malpighi University Hospital, Bologna, Italy. · Digestive and Liver Disease, ENETS Center of Excellence Sant'Andrea Hospital - Sapienza University of Rome, Italy. Electronic address: fpanzuto@ospedalesantandrea.it. ·Pancreatology · Pubmed #29361429.

ABSTRACT: INTRODUCTION: Besides data reported in a Phase-III trial, data on sunitinib in pancreatic Neuroendocrine Tumors (panNETs) are scanty. AIM: To evaluate sunitinib efficacy and tolerability in panNETs patients treated in a real-world setting. PATIENTS AND METHODS: Retrospective analysis of progressive panNETs treated with sunitinib. Efficacy was assessed by evaluating progression-free survival, overall survival, and disease control (DC) rate (stable disease (SD) + partial response + complete response). Data are reported as median (25th-75th IQR). RESULTS: Eighty patients were included. Overall, 71.1% had NET G2, 26.3% had NET G1, and 2.6% had NET G3 neoplasms. A total of 53 patients (66.3%) had received three or more therapeutic regimens before sunitinib, with 24 patients (30%) having been treated with four previous treatments. Median PFS was 10 months. Similar risk of progression was observed between NET G1 and NET G2 tumors (median PFS 11 months and 8 months, respectively), and between patients who had received ≥ 3 vs ≤ 2 therapeutic approaches before sunitinib (median PFS 9 months and 10 months, respectively). DC rate was 71.3% and SD was the most frequent observed response, occurring in 43 pts (53.8%). Overall, 59 pts (73.8%) experienced AEs, which were grade 1-2 in 43 of them (72.9%), grade 3 in 15 pts (25.4%), and grade 4 in one patient (1.7%). Six pts (7.5%) stopped treatment due to toxicity. CONCLUSIONS: The present real-world experience shows that sunitinib is a safe and effective treatment for panNETs, even in the clinical setting of heavily pre-treated, progressive diseases.

7 Article Correlation between MGMT promoter methylation and response to temozolomide-based therapy in neuroendocrine neoplasms: an observational retrospective multicenter study. 2018

Campana, Davide / Walter, Thomas / Pusceddu, Sara / Gelsomino, Fabio / Graillot, Emmanuelle / Prinzi, Natalie / Spallanzani, Andrea / Fiorentino, Michelangelo / Barritault, Marc / Dall'Olio, Filippo / Brighi, Nicole / Biasco, Guido. ·Department of Medical and Surgical Sciences, S.Orsola-Malpighi University Hospital, Bologna, Italy. davide.campana@unibo.it. · Hospices Civils de Lyon, University Hospital of Lyon, Lyon, France. · Department of Medical Oncology, ENETS Center of Excellence, Fondazione IRCCS 'Istituto Nazionale dei Tumori', Milan, Italy. · Department of Oncology and Haematology, Division of Oncology, University Hospital of Modena, Modena, Italy. · Department of Experimental, Diagnostic and Specialty Medicine, S.Orsola-Malpighi University Hospital, Bologna, Italy. ·Endocrine · Pubmed #29150792.

ABSTRACT: PURPOSE: Temozolomide (TEM) based therapy has been reported being effective in the treatment of metastatic neuroendocrine neoplasms (NEN), with response rates ranging from 30 to 70%. Among patients affected by advanced glioblastoma or melanoma and treated with TEM, loss of tumoral O6-methylguanine DNA methyltransferase (MGMT) is correlated with improved survival. In NEN patients, the role of MGMT deficiency in predicting clinical outcomes of TEM treatment is still under debate. METHODS: In this study we evaluated 95 patients with advanced NENs undergoing treatment with TEM-based therapy. MGMT promoter methylation status was evaluated with two techniques: methylation specific-polymerase chain reaction or pyrosequencing. RESULTS: Treatment with TEM-based therapy was associated with an overall response rate of 27.4% according to RECIST criteria (51.8% of patients with and 17.7% without MGMT promoter methylation). Response to therapy, progression free survival and overall survival was correlated to MGMT status at univariate and multivariate analysis. Methylation of MGMT promoter could be a strong predictive factor of objective response and an important prognostic factor of a longer PFS and OS. CONCLUSION: According to our results, MGMT methylation status, evaluated with methylation specific-polymerase chain reaction or pyrosequencing, should have an important role in patients with metastatic NENs, in order to guide therapeutic options. These results need further confirmation with prospective studies.

8 Article Good performance of platinum-based chemotherapy for high-grade gastroenteropancreatic and unknown primary neuroendocrine neoplasms. 2018

Brandi, Giovanni / Paragona, Marco / Campana, Davide / Brighi, Nicole / Bondi, Arrigo / Pantaleo, Maria Abbondanza / Corbelli, Jody / Barbera, Maria Aurelia / Biasco, Guido. ·a Department of Experimental, Diagnostic and Speciality Medicine , 'L. & A. Seragnoli' Institute of Hematology and Medical Oncology, Sant'Orsola-Malpighi Hospital , Bologna , Italy. · b Interdepartmental Center for Cancer Research (CIRC) , Sant'Orsola-Malpighi Hospital , Bologna , Italy. · c Internal Medicine Unit, Medical and Surgical Sciences Department , Sant'Orsola-Malpighi Hospital , Bologna , Italy. · d Cytological and Pathological Anatomy Unit , Maggiore Hospital , Bologna , Italy. ·J Chemother · Pubmed #28641483.

ABSTRACT: To evaluate efficacy and safety of platinum and etoposide combination in the treatment of advanced gastroenteropancreatic (GEP) and unknown primary (CUP) neuroendocrine carcinomas (NEC), we analysed the records of 21 consecutive patients treated with this regimen from 1999 to 2012. Objective responses were obtained in 11 patients (52%) and disease stability (DS) in 5 (24%). Median progression-free survival (PFS) was 7 months (95% CI, 5.33-8.66). Median overall survival (OS) was 16 months (95% CI, 14.97-17.03). Patients with limited liver disease had a significantly (p = 0.002) better PFS than patients with extrahepatic disease at diagnosis with 9 months (95% CI, 7.14-10.85) vs. 4 months (95% CI, 1.60-6.40). Two patients experienced durable complete response (30 and 90 months). The most common grade 3-4 toxicities were neutropenia (61%), anaemia (50%), nausea and vomiting (27%) and fatigue (22%). The platinum plus etoposide regimen has an acceptable toxicity profile and is effective in patients with GEP and CUP-NECs.

9 Article Is surgery the best treatment for sporadic small (≤2 cm) non-functioning pancreatic neuroendocrine tumours? A single centre experience. 2017

Ricci, Claudio / Taffurelli, Giovanni / Campana, Davide / Ambrosini, Valentina / Pacilio, Carlo Alberto / Pagano, Nico / Santini, Donatella / Brighi, Nicole / Minni, Francesco / Casadei, Riccardo. ·Department of Internal Medicine and Surgery (DIMEC), Alma Mater Studiorum, University of Bologna, S.Orsola-Malpighi Hospital, Italy. · Department of Haematology and Oncology (DIMES), Alma Mater Studiorum, University of Bologna, S.Orsola-Malpighi Hospital, Italy. · Department of Internal Medicine and Surgery (DIMEC), Alma Mater Studiorum, University of Bologna, S.Orsola-Malpighi Hospital, Italy. Electronic address: riccardo.casadei@unibo.it. ·Pancreatology · Pubmed #28320587.

ABSTRACT: BACKGOUND: There is currently there is substantial controversy regarding the best management of non-functioning pancreatic neuroendocrine tumours ≤2 cm. METHODS: Retrospective study involving 102 surgically treated patients affected by non-functioning pancreatic neuroendocrine tumours. Patients having small tumours (≤2 cm) (Group A) and those having large tumours (>2 cm) (Group B) were compared regarding demographics, clinical and pathological factors with the aim of evaluating the risk of malignancy and survival times. RESULTS: The small tumours were T3-4 in 11% and G2-3 in 36.6% of cases; lymph node and distant metastases were present in 31% and 8% of the cases, respectively. When small and large tumours were compared, significant differences were found in relation to the presence of symptoms (P = 0.012), tumour status (P > 0.001), grading (P > 0.001) and years lost due to disability (P = 0.002). Multivariate analysis of the factors predicting malignancy and survival times showed that tumour size was related only to grading (P < 0.001). The years of life lost and disability adjusted life years were influenced by age at of diagnosis, the presence of symptoms and years lost due to disability only by grading. CONCLUSIONS: Tumour size alone did not seem to be reliable in predicting malignancy because, first, small tumours (≤2 cm) could present lymph node or distant metastases, and could be G2-3 in a non-negligible percentage of cases and second, their risk of malignancy and survival time are similar to large tumours. Additional parameters have to be considered in order to establish the proper management of small tumours, such as age at diagnosis, presence of symptoms and grading.

10 Article Everolimus in Pancreatic Neuroendocrine Carcinomas G3. 2017

Panzuto, Francesco / Rinzivillo, Maria / Spada, Francesca / Antonuzzo, Lorenzo / Ibrahim, Toni / Campana, Davide / Fazio, Nicola / Delle Fave, Gianfranco. ·From the *Digestive and Liver Diseases, Sant'Andrea Hospital-Sapienza University of Roma, Rome; †Unit of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, Milan; ‡Medical Oncology, Azienda Ospedaliero-Universitaria Careggi, Florence, and Department of Medical Biotechnologies, University of Siena, Siena; §Osteoncology and Rare Tumors Center, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), Meldola (FC); and ∥Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy. ·Pancreas · Pubmed #28099254.

ABSTRACT: OBJECTIVE: The aim of this study was to investigate everolimus efficacy in well-moderately differentiated pancreatic NEC (pNEC) G3. METHODS: This was a retrospective analysis of patients with pNEC G3 and Ki67 20% to 55% treated with everolimus. RESULTS: Fifteen patients with median Ki67 30% and Eastern Cooperative Oncology Group performance status 0 to 1 were evaluated. Of these, 4 patients received everolimus as first-line treatment, whereas 11 had been pretreated with chemotherapy or peptide receptor radionuclide therapy. Median progression-free survival was 6 months, and median overall survival was 28 months. Eleven patients achieved disease stabilization (DS) at 3 month follow-up. Six patients (40%) maintained DS for at least 12 months. Three of 4 patients who received everolimus as first-line therapy had sustained DS (progression-free survival, 12, 17, and 22 months). The safety profile was consistent with that previously reported, with adverse events occurring in 9 patients (66.7%). CONCLUSIONS: This study suggests that everolimus is active in pNEC G3 with well-moderately differentiated morphology and Ki67 less than 55%, in which more toxic systemic chemotherapy is, to date, the only available treatment.

11 Article Validation of the 2010 WHO classification and a new prognostic proposal: A single centre retrospective study of well-differentiated pancreatic neuroendocrine tumours. 2016

Ricci, Claudio / Casadei, Riccardo / Taffurelli, Giovanni / Campana, Davide / Ambrosini, Valentina / Pagano, Nico / Santini, Donatella / De Giorgio, Roberto / Ingaldi, Carlo / Tomassetti, Paola / Zani, Elia / Minni, Francesco. ·Department of Internal Medicine and Surgery (DIMEC), Alma Mater Studiorum, University of Bologna, S.Orsola-Malpighi Hospital, Italy. Electronic address: claudiochir@gmail.com. · Department of Internal Medicine and Surgery (DIMEC), Alma Mater Studiorum, University of Bologna, S.Orsola-Malpighi Hospital, Italy. · Department of Haematology and Oncology (DIMES), Alma Mater Studiorum, University of Bologna, S.Orsola-Malpighi Hospital, Italy. ·Pancreatology · Pubmed #26924664.

ABSTRACT: BACKGOUND: In 2010, the World Health Organization (WHO) modified the classification for pancreatic neuroendocrine tumours (NETs). Recently, some modifications were proposed to improve its prognostic value. The aim of this study was to test the prognostic value of both the original and the modified 2010 WHO grading systems. METHODS: One hundred and twenty consecutive patients surgically resected for well-differentiated NETs were evaluated in multivariate Cox regression models. Age, sex, hormonal status, size, lymph node ratio, stage, margin status and grading were evaluated in order to predict disease-free survival (DFS). Four models were evaluated: model 1: grading according to the 2010 WHO; model 2: modified grading with cut-off at 5% of the Ki-67 index; model 3: modified grading in which the G2 category was divided into two subgroups (2-5% and 5-20%) and model 4: the Ki-67 index as a continuous variable. Decision curve analysis (DCA) was carried out to evaluate the clinical utility of the various cut-offs. RESULTS: All the grading systems remained independent factors in predicting DFS. Model 2 (c index = 0.814 and P = 0.012) and model 3 (c index = 0.865 and P = 0.015) showed higher predictive powers with respect to model 1 (c index = 0.799). Model 4 had a high predictive value (c index 0.848, P = 0.013). Decision curve analysis confirmed that biological behaviour represented the best prognostic parameter. CONCLUSION: This study presented some limitations: single centre, retrospective design and a long period of enrolment. The result showed that, by increasing the cut-off of the G2 category to 5% or by creating two subgroups in the G2 category, it was possible to obtain a better stratification of patients.

12 Article Prognostic Value of 68Ga-DOTANOC PET/CT SUVmax in Patients with Neuroendocrine Tumors of the Pancreas. 2015

Ambrosini, Valentina / Campana, Davide / Polverari, Giulia / Peterle, Chiara / Diodato, Stefania / Ricci, Claudio / Allegri, Vincenzo / Casadei, Riccardo / Tomassetti, Paola / Fanti, Stefano. ·Nuclear Medicine, Department of Experimental Diagnostic and Specialized Medicine, University of Bologna and S. Orsola-Malpighi Hospital, Bologna, Italy; and valentina.ambrosini@unibo.it. · Department of Medical and Surgical Sciences, S. Orsola-Malpighi University Hospital, Bologna, Italy. · Nuclear Medicine, Department of Experimental Diagnostic and Specialized Medicine, University of Bologna and S. Orsola-Malpighi Hospital, Bologna, Italy; and. ·J Nucl Med · Pubmed #26405169.

ABSTRACT: METHODS: Among the patients who underwent (68)Ga-DOTANOC PET/CT, we retrospectively collected the data of those who had G1 or G2 pNET (2010 World Health Organization classification), presented with disease on PET/CT and CT, and had at least 6 mo of follow-up. Patients with multiple endocrine neoplasia were excluded. RESULTS: Overall, 43 patients were included. No significant differences in SUVmax were observed with respect to sex, tumor syndrome, stage, World Health Organization classification, or Ki-67. During follow-up (median, 20 mo), 11 patients (35.6%; median, 33 mo; interquartile range, 20-48 mo) had stable disease and 32 (74.4%; median, 19 mo; interquartile range, 14-26 mo) had progressive disease. SUVmax at 24 mo of follow-up was significantly higher (P = 0.022) in patients with stable disease than in patients with progressive disease. The best SUVmax cutoff ranged from 37.8 to 38.0. The major risk factors for progression included an SUVmax of no more than 37.8 (hazard ratio, 3.09; P = 0.003), a Ki-67 of more than 5% (hazard ratio, 2.89; P = 0.009), and medical therapy alone (hazard ratio, 2.36; P = 0.018). Advanced stage (IV) (P = 0.026), an SUVmax of less than 37.8 (P = 0.043), and medical therapy alone (P = 0.015) were also confirmed at multivariate analysis. Median progression-free survival was 23 mo. Significant differences in progression-free survival were observed in relationship to Ki-67 (median, 45 mo for Ki-67 ≤ 5% and 20 mo for Ki-67 > 5%; P = 0.005), SUVmax (<37.8 vs. >38.0: 16.0 vs. 27.0 mo; P = 0.002), and type of therapy (medical vs. peptide receptor radionuclide therapy: 16.0 vs. 26.0 mo; P = 0.014). CONCLUSION: (68)Ga-DOTANOC SUVmax is a relevant prognostic factor in patients with G1 and G2 pNET, and its routine use will improve disease characterization and management in these patients, who may present with atypical cases showing heterogeneous clinical behavior.

13 Article Efficacy and cost-effectiveness of immediate surgery versus a wait-and-see strategy for sporadic nonfunctioning T1 pancreatic endocrine neoplasms. 2015

Cucchetti, Alessandro / Ricci, Claudio / Ercolani, Giorgio / Campana, Davide / Cescon, Matteo / D'Ambra, Marielda / Pinna, Antonio Daniele / Minni, Francesco / Casadei, Riccardo. ·Department of Medical and Surgical Sciences - DIMEC, S. Orsola-Malpighi Hospital, Alma Mater Studiorum, University of Bologna, Bologna, Italy. ·Neuroendocrinology · Pubmed #25228538.

ABSTRACT: BACKGROUND: Whether patients with small (<2 cm), sporadic nonfunctioning pancreatic endocrine tumors (NF-PETs) should directly undergo pancreatic surgery or should be followed longitudinally to detect growth and malignancy still has to be defined. STUDY DESIGN: Based on the pertinent literature of the past decade, a Markov model was developed to investigate this issue. In the wait-and-see strategy arm, surgery was performed if the tumor attained a size ≥2 cm or surpassed 20% of the initial size. In a Monte Carlo probabilistic analysis, 100 hypothetical patients undergoing a wait-and-see strategy were compared to 100 patients directly undergoing surgery, with the aim of investigating the efficacy and cost-effectiveness of the two strategies. RESULTS: During the postdiagnostic lifetime, 63 NF-PETs in the wait-and-see group showed significant growth and underwent surgery: 38 were stage I, 10 were stage II, 15 were stage III and none were stage IV. In the base-case scenario, the mean life expectancy and quality-adjusted life expectancy were found to be superior after immediate surgery [26.1 years and 11.8 quality-adjusted life years (QALYs)] than with the wait-and-see strategy (22.1 years and 8.3 QALYs) as the consequence of ageing during the wait-and-see follow-up which increased mortality due to surgery, when surgery was needed. The model was sensitive to starting age and length of follow-up; in particular, for patients >65 years of age, the two strategies provided similar results but the wait-and-see strategy was more cost-effective. CONCLUSIONS: The wait-and-see strategy for NF-PETs <2 cm represents a reasonable approach in patients over 65 years of age; otherwise, immediate surgery is preferable.

14 Article 68Ga DOTANOC PET/CT detects primary malignant insulinoma. 2015

Ambrosini, Valentina / Campana, Davide / Nanni, Cristina / Marzola, Maria Cristina / Rubello, Domenico / Fanti, Stefano. ·From the Departments of *Nuclear Medicine, and †Internal Medicine, Sant'Orsola-Malpighi University Hospital, Bologna; and ‡Department of Nuclear Medicine, Santa Maria della Misericordia, Rovigo, Italy. ·Clin Nucl Med · Pubmed #24830876.

ABSTRACT: Malignant insulinoma is an extremely rare pancreatic tumor variant characterized by an aggressive clinical behavior with local and distant spread. Delays in the diagnosis are common because symptoms usually precede tumor detection and may be misattributed. Aggressive surgical resection is the primary treatment option; therefore accurate tumor localization is important for appropriate management. Although somatostatin receptor imaging has a limited role in the visualization of benign insulinoma (characterized by a low expression of somatostatin receptors), it can still have a role in the detection of malignant forms.

15 Article The role of lymph node ratio in recurrence after curative surgery for pancreatic endocrine tumours. 2013

Ricci, Claudio / Casadei, Riccardo / Taffurelli, Giovanni / Buscemi, Salvatore / D'Ambra, Marielda / Monari, Francesco / Santini, Donatella / Campana, Davide / Tomassetti, Paola / Minni, Francesco. ·Department of Internal Medicine, Emergency and Surgery (DIMES), Alma Mater Studiorum, University of Bologna, S.Orsola-Malpighi Hospital, Italy. Electronic address: claudiochir@gmail.com. ·Pancreatology · Pubmed #24280574.

ABSTRACT: BACKGROUND: The prognostic role of lymph nodes metastasis in pancreatic neuroendocrine tumours is unclear. METHODS: Retrospective study of 53 patients who underwent a curative standard resection for pancreatic neuroendocrine tumours. The endpoint was to define the role of the lymph nodes ratio in recurrence after curative surgery. The following data were considered as possible factors for predicting the risk of recurrence: gender, age, presence of symptoms, hormonal status, site of tumours, type of resection, size of the tumours, radical resection, pathological T, N and M stage, the Ki67 index, the number of lymph nodes harvested, the number of metastatic lymph nodes and the lymph node ratio. Recurrence rate and time of recurrence were evaluated. RESULTS: Twelve (26.4%) patients developed a recurrence with a median time of 42.8 (1-305) months. At multivariate analysis, the only factors related to recurrence were: size of lesions (HR 1.1, C.I. 95% 1.0-1.1, P = 0.011), Ki67 ≥ 5% (HR 3.6, C.I. 95% 1.3-10, P = 0.014) and LNR > 0.07 (HR 5.2, C.I. 95% 1.1-25, P = 0.045). CONCLUSIONS: Our study confirmed that the lymph nodes ratio played an important role in the recurrence rate and suggested that a low number of metastatic lymph nodes reduced the disease free survival.

16 Article Radiolabelled somatostatin analogue treatment in gastroenteropancreatic neuroendocrine tumours: factors associated with response and suggestions for therapeutic sequence. 2013

Campana, Davide / Capurso, Gabriele / Partelli, Stefano / Nori, Francesca / Panzuto, Francesco / Tamburrino, Domenico / Cacciari, Giulia / Delle Fave, Gianfranco / Falconi, Massimo / Tomassetti, Paola. ·Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy. davide.campana@unibo.it ·Eur J Nucl Med Mol Imaging · Pubmed #23619938.

ABSTRACT: PURPOSE: Peptide receptor radionuclide therapy (PRRT) is a relatively new treatment modality for patients with unresectable or metastatic gastroenteropancreatic neuroendocrine tumours (GEP NETs). The aim of this study was to determine the time to progression of patients treated with PRRT and to identify the prognostic factors related to treatment response. METHODS: Patients with sporadic GEP NETs prospectively treated with PRRT were retrospectively analysed. The primary end point was progression-free survival (PFS). RESULTS: A total of 69 patients (37 men and 32 women; 45 with pancreatic and 24 with gastrointestinal lesion; 22 NET G1 and 41 NET G2) were treated with (90)Y or (177)Lu. The objective response rate was 27.5% (partial response, PR), while 50.7% had stable disease and 23.2% had progressive disease. Significant differences in PFS were observed in relationship to the stage of the disease (44 months for stage III, 23 months for stage IV), the evidence of a PR 6 months after the end of the PRRT (39 months in patients with a PR, 22 months in patients without a PR) and previous transarterial chemoembolization (TACE, yes 13 months vs no 31 months). Stage IV, NET G2 and previous TACE were found to be significant factors for tumour progression at multivariate analysis. CONCLUSION: Low tumour burden and a low proliferation index represent independent prognostic factors for long PFS, while previous chemoembolization techniques represent independent prognostic factors for early tumour progression and shorter PFS. Our data suggest that chemoembolization techniques to reduce the hepatic tumour burden should be avoided.

17 Article Treatment of malignant pancreatic neuroendocrine neoplasms: middle-term (2-year) outcomes of a prospective observational multicentre study. 2013

Zerbi, Alessandro / Capitanio, Vanessa / Boninsegna, Letizia / Delle Fave, Gianfranco / Pasquali, Claudio / Rindi, Guido / Campana, Davide / Falconi, Massimo / Anonymous1740752. ·Pancreatic Surgery, Department of Surgery, Humanitas Clinical and Research Center, Milan, Italy. ·HPB (Oxford) · Pubmed #23472667.

ABSTRACT: BACKGROUND: Information on malignant pancreatic neuroendocrine neoplasms (pNENs) is mostly from retrospective studies in highly selected patients. The aim of this prospective, multicentre study was to assess treatment and outcomes of malignant pNENs in clinical practice. PATIENTS AND METHODS: Consecutive patients with newly diagnosed, histologically-proven pNENs were included and followed-up for 2 years. Tumours were defined as malignant when nodal or distant metastases were present or invasion of extrapancreatic structures/organs was evident. RESULTS: A total of 140 patients with malignant pNENs were included. Ninety-eight patients (70.0%) underwent a surgical resection (76 radical and 22 palliative). Other non-surgical treatments were used in 101 patients (72.1%): somatostatin analogues (n = 63), chemotherapy (n = 30), ablative treatments (n = 15) and peptide-receptor radionuclide therapy (n = 14). No relationship was observed between the 2010 WHO classification and type of treatment. A surgical resection was more often performed in incidentally detected tumours located in the pancreas body tail. Two-year progression-free survival was 63.8%: 82% after a radical resection, 44% after a palliative resection and 41% without a resection. A radical resection and Ki67 proliferative index >5% and >10% were the only significant prognostic determinants in multivariate analysis. CONCLUSIONS: A radical resection is the cornerstone treatment of malignant pNENs and represents, together with Ki67 assessment, the most powerful prognostic factor for 2-year outcomes.

18 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.

19 Article Metastatic and locally advanced pancreatic endocrine carcinomas: analysis of factors associated with disease progression. 2011

Panzuto, Francesco / Boninsegna, Letizia / Fazio, Nicola / Campana, Davide / Pia Brizzi, Maria / Capurso, Gabriele / Scarpa, Aldo / De Braud, Filippo / Dogliotti, Luigi / Tomassetti, Paola / Delle Fave, Gianfranco / Falconi, Massimo. ·II School of Medicine, Sapienza University of Roma, Sant'Andrea Hospital, Via di Grottarossa 1035, Rome, Italy. ·J Clin Oncol · Pubmed #21555696.

ABSTRACT: PURPOSE: Knowledge of clinical course of pancreatic endocrine carcinomas (PECs) is poor. This study aimed to determine the time to progression of advanced PECs, and to identify predictors capable of selecting subgroups with higher risk of progression. PATIENTS AND METHODS: In this multicenter retrospective analysis, patients with advanced PECs were enrolled. Staging was according to European Neuroendocrine Tumors Society guidelines. Grading was based on proliferation index using Ki67 immunohistochemistry. The primary end point was progression-free survival (PFS), which was assessed using the Kaplan-Meier method. The Cox regression proportional hazard model was used to identify predictors for tumor progression. RESULTS: Two hundred two patients with PECs were enrolled, including 172 with well-differentiated and 30 with poorly differentiated endocrine carcinomas. There were 34 patients with stage III and 168 with stage IV tumors. G1 tumors were present in 19.7% of patients, whereas 60.1% of patients had G2 tumors, and the remaining 20.2% had G3 tumors. Disease progression occurred in 166 patients (82.2%), at a median interval of 10 months (interquartile range, 5 to 22) from diagnosis. Median PFS was 14 months. Different PFS were observed depending on G grade (P < .001) and tumor differentiation (P < .001) and in patients who did not receive any antitumor treatment (P = .002). The major risk factor for progression was the proliferation index Ki67 (hazard ratio, 1.02 for each increasing unit; P < .001). Overall 5-year survival was 44.1%. CONCLUSION: The vast majority of patients with advanced PECs undergo disease progression. The major risk factor for progression is Ki67 index, which should lead physicians dealing with PECs to plan appropriate follow-up programs and therapeutic strategies.

20 Article Are there prognostic factors related to recurrence in pancreatic endocrine tumors? 2010

Casadei, Riccardo / Ricci, Claudio / Pezzilli, Raffaele / Campana, Davide / Tomassetti, Paola / Calculli, Lucia / Santini, Donatella / D'Ambra, Marielda / Minni, Francesco. ·Dipartimenti di Scienze Chirurgiche, Alma Mater Studiorum, Università di Bologna, Bologna, Italy. riccardo.casadei@aosp.bo.it ·Pancreatology · Pubmed #20299821.

ABSTRACT: AIMS: The aim of this study was to evaluate the rate, site, time of recurrence and prognostic factors related to the appearance of recurrences in patients affected by pancreatic endocrine tumors (PETs). METHODS: Data from 67 consecutive patients with PETs who underwent R0 resection were analyzed. The prognostic factors considered were: gender, age, type of tumor, presence of symptoms, size of tumor, tumor node metastasis (TNM) stage, WHO classification and adjuvant therapy. RESULTS: The recurrence rate was 24.6%, with a mean time of 7.3 +/- 4.5 years. The majority were in the liver (75% of cases) and were rarely local (25%). Univariate analysis of the prognostic factors showed that the risk of recurrences is significantly higher in PETs in MEN-1 syndrome, in tumor size > or =4 cm, in the presence of liver metastases, in TNM stages III-IV and, finally, in PD-Cas and WD-Cas. Multivariate Cox regression analysis showed that only MEN-1 syndrome and the WHO classification were independent predictors of an increased risk of recurrence. CONCLUSIONS: Several prognostic factors were related to recurrences in PETs. MEN-1 syndrome and the WHO classification can be considered independent factors of an increased risk of recurrence. and IAP.

21 Article Serum leptin, but not adiponectin and receptor for advanced glycation end products, is able to distinguish autoimmune pancreatitis from both chronic pancreatitis and pancreatic neoplasms. 2010

Pezzilli, Raffaele / Barassi, Alessandra / Corsi, Massimiliano M / Morselli-Labate, Antonio M / Campana, Davide / Casadei, Riccardo / Santini, Donatella / Corinaldesi, Roberto / D'Eril, Gianvico Melzi. ·Department of Digestive Diseases and Internal Medicine, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy. raffaele.pezzilli@aosp.bo.it ·Scand J Gastroenterol · Pubmed #19883273.

ABSTRACT: OBJECTIVE: Serum leptin and adiponectin determinations have been proposed as markers for distinguishing pancreatic cancer and chronic pancreatitis from autoimmune pancreatitis; however, no studies exist in patients with autoimmune pancreatitis and in those with intraductal papillary mucinous tumors of the pancreas. The aim of this paper was to evaluate the circulating concentrations of receptor for advanced glycation end products (RAGE), leptin and adiponectin in patients with chronic pancreatic diseases. MATERIAL AND METHODS: Seventy-five consecutive patients with chronic pancreatic diseases (47 males, 28 females; mean age 67.0 +/- 13.2 years; range 37-97 years) were studied: six (8.0%) had autoimmune pancreatitis, 23 (30.7%) had chronic pancreatitis, 34 (45.3%) had pancreatic cancer and the remaining 12 (16.0%) had intraductal papillary mutinous tumors of the pancreas. Leptin, adiponectin and RAGE were determined in serum using commercially available kits. The leptin concentrations were normalized to the lower and upper reference limits because of the different gender reference ranges. RESULTS: Normalized leptin concentrations were significantly lower in chronic pancreatitis patients (0.53 +/- 1.28; p = 0.008) and in those with pancreatic cancer (0.12 +/- 0.33; p < 0.001) compared to the overall population (0.58 +/- 1.23), whereas autoimmune pancreatitis patients had significantly higher concentrations of this protein (2.18 +/- 2.56; p = 0.004) compared to the overall population. RAGE and adiponectin concentrations were similar among the four groups of patients studied. Among the clinical variables considered, only pain was significantly related to leptin concentrations (patients with pain 0.18 +/- 0.54, patients without pain 1.07 +/- 1.64; p = 0.001). CONCLUSION: Serum leptin seems to be a good serum marker for differentiating autoimmune pancreatitis patients from those with chronic pancreatitis and pancreatic cancer.

22 Article Patient-reported outcomes in subjects with neuroendocrine tumors of the pancreas. 2009

Pezzilli, Raffaele / Campana, Davide / Morselli-Labate, Antonio-M / Fabbri, Maria-C / Brocchi, Emilio / Tomassetti, Paola. ·Department of Digestive Diseases and Internal Medicine, Sant'Orsola-Malpighi Hospital, University of Bologna, Via Massarenti, 9, Bologna 40138, Italy. raffaele.pezzilli@aosp.bo.it ·World J Gastroenterol · Pubmed #19860000.

ABSTRACT: AIM: To assess the patient-reported outcomes (PROs) of pancreatic neuroendocrine tumor (PNET) patients. METHODS: Fifty-one consecutive patients (21 male, 30 female, 61.0 +/- 10.3 years) with proven PNETs were studied. An SF-12 questionnaire capable of exploring the physical (PCS) and mental (MCS) aspects of daily life was used. Four questionnaires were also used [12 items General Health Questionnaire (GHQ-12) for non-psychotic psychiatric disorders, State Trait Anxiety Inventory (STAI) Y-1 and Y-2 for anxiety and BDI-II for depressive symptoms] to explore the psychological aspects of the disease. Forty-four sex- and age-matched Italian normative subjects were included and evaluated using the SF-12, STAI Y-1 and Y-2 questionnaires. RESULTS: Seven patients refused to participate to the study; they were clinically similar to the 44 participants who agreed to complete the questionnaires. PNET patients had a PCS score (44.7 +/- 11.0) were not significantly different from the norms (46.1 +/- 9.9, P = 0.610), whereas the MCS score was significantly lower in patients (42.4 +/- 13.0) as compared to the norms (48.2 +/- 9.8, P = 0.036). GHQ-12 identified 11 patients (25.0%) as having non-psychotic psychiatric disorders. The STAI scores were similar in the patients and in the normative population. Finally, BDI-II identified eight patients (18.2%) with moderate depression and 9 (20.5%) with mild depression whereas 27 patients (61.4%) had no depression. CONCLUSION: The PNET patients had a good physical but an impaired mental component of their quality of life; in addition, mild or moderate depressive symptoms are present in about 40% of PNET patients.

23 Article Value of both WHO and TNM classification systems for patients with pancreatic endocrine tumors: results of a single-center series. 2009

Casadei, Riccardo / Ricci, Claudio / Pezzilli, Raffaele / Campana, Davide / Tomassetti, Paola / Calculli, Lucia / Santini, Donatella / Antonacci, Nicola / Minni, Francesco. ·Dipartimento di Scienze Chirurgiche e Anestesiologiche, Chirurgia Generale-Minni, Alma Mater Studiorum, Università di Bologna, Policlinico S.Orsola-Malpighi, Via Massarenti n.9, 40138 Bologna, Italy. riccardo.casadei@aosp.bo.it ·World J Surg · Pubmed #19655196.

ABSTRACT: OBJECTIVES: This study was designed to evaluate the clinical relevance of the World Health Organization (WHO) and tumor node metastasis (TNM) classifications in patients affected by pancreatic endocrine tumors. METHODS: Data from 76 consecutive patients with pancreatic endocrine tumors who underwent surgery were analyzed. RESULTS: Well-differentiated tumors were observed more frequently (57.9%) than well or poorly differentiated carcinomas (26.3% and 15.8%, respectively). The TNM stage was I in 27.6%, II in 39.5%, III in 19.7%, and IV in 13.2%. Univariate analysis of disease-specific survival showed that patients with stages I-II had a significantly better survival rate than those with stages III-IV (hazard ratio (HR), 12.46; 95% confidence interval (CI), 1.53-101.32; P = 0.018; HR, 25.74; 95% CI, 3.07-216.07; P = 0.003, respectively). Regarding the WHO classification, poorly differentiated carcinomas had the worst prognosis (HR, 79.13; 95% CI, 9.99-626.60; P < 0.001). Multivariate Cox regression analysis of disease-specific survival showed that the WHO classification is the only independent factors of improved survival: both poorly and well-differentiated carcinomas had an increased risk of death compared with WDTs (HR, 100.42; 95% CI, 12.16-829.40; P < 0.001; HR, 10.73; 95% CI, 1.12-104.17; P = 0.040, respectively). TNM classification and the WHO system are highly correlated (P < 0.001). CONCLUSIONS: TNM stage and the WHO classification seems to be equally reliable, even if TNM classification tends to understage the patients classified using the WHO system.

24 Article Comparison between 68Ga-DOTA-NOC and 18F-DOPA PET for the detection of gastro-entero-pancreatic and lung neuro-endocrine tumours. 2008

Ambrosini, Valentina / Tomassetti, Paola / Castellucci, Paolo / Campana, Davide / Montini, Giancarlo / Rubello, Domenico / Nanni, Cristina / Rizzello, Anna / Franchi, Roberto / Fanti, Stefano. ·Unità Operativa di Medicina Nucleare, Azienda Ospedaliero Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Padiglione 30, Via Massarenti 9, 40138, Bologna, Italy. valentina.ambrosini@aosp.bo.it ·Eur J Nucl Med Mol Imaging · Pubmed #18418596.

ABSTRACT: PURPOSE: (18)F-FDG positron emission tomography (PET) value for the assessment of neuro-endocrine tumours (NET) is limited. Preliminary studies indicate that (18)F-DOPA and (68)Ga-DOTA-NOC are more accurate for disease assessment and (68)Ga-DOTA peptides provide additional data on receptor status that are crucial for targeted radionuclide therapy. At present, there are no comparative studies investigating their role in NET. AIM: The aim of this study was to compare (68)Ga-DOTA-NOC and (18)F-DOPA for the evaluation of gastro-entero-pancreatic and lung neuro-endocrine tumours. MATERIALS AND METHODS: Thirteen patients with biopsy-proven NET (gastro-entero-pancreatic or pulmonary) were prospectively enrolled and scheduled for (18)F-DOPA and (68)Ga-DOTA-NOC PET. PET results obtained with both tracers were compared with each other, with other conventional diagnostic procedures (CT, ultrasound) and with follow-up (clinical, imaging). RESULTS: The most common primary tumour site was the pancreas (8/13) followed by the ileum (2/13), the lung (2/13) and the duodenum (1/13). The carcinoma was well differentiated in 10/13 and poorly differentiated in 3/13 cases. (68)Ga-DOTA-NOC PET was positive, showing at least one lesion, in 13/13 cases while (18)F-DOPA PET was positive in 9/13. On a lesions basis, (68)Ga-DOTA-NOC identified more lesions than (18)F-DOPA (71 vs 45), especially at liver, lung and lymph node level. (68)Ga-DOTA-NOC correctly identified the primary site in six of eight non-operated cases (in five cases, the primary was surgically removed before PET), while (18)F-DOPA identified the primary only in two of eight cases. CONCLUSIONS: Although the patients studied are few and heterogeneous, our data show that (68)Ga-DOTA-NOC is accurate for the detection of gastro-entero-pancreatic and lung neuro-endocrine tumours in either the primary or metastatic site and that it offers several advantages over (18)F-DOPA.

25 Article Multiple gastric endocrine tumours and gastrinomas of the duodenum in a patient with ZES MEN 1. 2008

Campana, D / Brocchi, E / Tomassetti, P. ·Department of Internal Medicine and Gastroenterology, University of Bologna, S.Orsola Malpighi Hospital, Via Massarenti 9, 40138 Bologna, Italy. ·Dig Liver Dis · Pubmed #18282753.

ABSTRACT: -- No abstract --

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