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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.

BACKGROUND: Information on the treatment of pancreatic endocrine tumours (PETs) comes mostly from small, retrospective, uncontrolled studies. METHODS: Newly diagnosed, histologically proven PETs, observed from June 2004 to March 2007 in 24 Italian centres, were included in a specific dataset. RESULTS: Three-hundred and ten patients (mean age 57.6 years, females 46.6%) were analysed. At the time of recruitment, 262 (84.5%) underwent surgery. The percentage of operated patients was 91.9% and 62.0% in surgical and non-surgical centres, respectively. A curative resection was carried out in 83.6% (n = 219) of cases, a palliative resection (debulking) in 10.7% (n = 28), an exploratory laparotomy in 4.6% (n = 12), and a bypass procedure in 1.1% (n = 3). Laparoscopy was performed in 8.0% (n = 21) of cases. Resection consisted of a pancreatoduodenectomy in 46 cases (21.0%), a distal pancreatectomy in 95 (43.4%), an enucleation in 50 (22.8%), a middle pancreatectomy in 16 (7.3%) and a total pancreatectomy in 12 (5.5%). Liver resection was associated with pancreatic resection in 26 cases (9.9%). Post-operative mortality was 1.5% and morbidity 39.7%, respectively. A curative resection was performed more frequently in asymptomatic, small, non-metastatic, benign and at uncertain behaviour tumours, with low Ki67 values. CONCLUSIONS: This study strongly indicates the fact that surgical resection represents the cornerstone treatment of PETs.

Objectives: Information on pancreatic endocrine tumors (PETs) comes mostly from small, retrospective, uncontrolled studies conducted on highly selected patients. The aim of the study was to describe the clinical and pathological features of PETs in a prospective, multicenter study.Methods: Newly diagnosed, histologically proven, sporadic PETs observed from June 2004 to March 2007 in 24 Italian centers were included in a specific data set.Results: Two hundred ninety-seven patients (mean age 58.614.7 years, females 51.2%, males 48.8%) were analyzed. In 73 cases (24.6%), the tumor was functioning (F) (53 insulinomas, 15 gastrinomas, 5 other syndromes) and in 232 (75.4%) it was non-functioning (NF); in 115 cases (38.7%), the diagnosis was incidental. The median tumor size was 20 mm (range 2-150). NF-PETs were significantly more represented among carcinomas (P0.001). Nodal and liver metastases were detected in 84 (28.3%) and 85 (28.6%) cases, respectively. The presence of liver metastases was significantly higher in the NF-PETs than in the F-PETs (32.1% vs. 17.8%; P0.05), and in the symptomatic than in the asymptomatic patients (34.6% vs. 19.1%; P

To analyze the characteristics and outcomes following enucleation and pancreatic resections of insulinomas.Retrospective cohort study; prospective database.Academic, tertiary, and referral centers.Consecutive patients with insulinomas (symptoms of hyperinsulinism and positive fasting glucose test) who underwent surgical treatment between January 1990 and December 2009.Operative morbidity, tumor recurrence, and survival after treatment.A total of 198 patients (58.5\% women; median age, 48 years) were identified. There were 175 (88\%) neuroendocrine tumors grade G1 and 23 (12\%) neuroendocrine tumors grade G2. Malignant insulinomas defined by lymph node/liver metastases were found in 7 patients (3.5\%). Multiple insulinomas were found in 8\% of patients, and 5.5\% of patients had multiple endocrine neoplasia type 1. Surgical procedures included 106 enucleations (54\%) and 92 pancreatic resections (46\%). Mortality was nil. Rate of clinically significant pancreatic fistula was 18\%. Enucleations had a higher reoperation rate compared with pancreatic resections (8.5\% vs 1\%; P = .02). Multiple endocrine neoplasia type 1 was significantly associated with younger age at onset (P < .005) and higher rates of malignancies and multiple lesions. Median follow-up was 65 months. Six patients (3\%; 5 patients had neuroendocrine tumors grade G2) developed tumor recurrence. Four patients (2\%) died of disease. New exocrine (1.5\%) and endocrine (4\%) insufficiencies were associated only with pancreatic resections.Outcomes following surgical resection of insulinomas are satisfactory, with no mortality and good functional results. Recurrence is uncommon (3\%), and it is more likely associated with neuroendocrine tumors grade G2. Insulinomas in multiple endocrine neoplasia type 1 are at higher risk for being malignant and multifocal, requiring pancreatic resections.