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Purpose: Ampullary neuroendocrine neoplasms (NENs) account for < 0.3% of gastrointestinal NENs. Surgical options include transduodenal ampullectomy/tumour excision or pancreaticoduodenectomy (PD). We report the experience of two high-volume pancreatic surgical centres of ampullary NENs.Methods: Clinical records of patients who underwent surgery for ampullary NENs (January 2007-November 2017) in the study centres were retrieved retrospectively. We evaluated clinical-pathological features, post-operative outcome and follow-up (FU).Results: Eighteen patients (9 M/9 F, averaging 62 years) were enrolled. All but one were non-functioning NENs; four (22%) patients presented with jaundice. Seven (39%) of the patients underwent ampullectomy/excision (median tumour size 1.5 cm), and 11 (61%) patients underwent PD (median tumour size 2.4 cm). The median operation time of ampullectomy/excision was 221 min with operative blood loss of 75 ml (vs. 506 min and 425 ml in PD). The median hospital stay was 10 days in both groups. Overall surgical morbidity was 33%, due to four biochemical leaks, one pancreatic fistula and one abdominal haemorrhage. No reoperations were needed. The median tumour size was 1.8 (range 0.5-6.7) cm. All G2-G3 NENs were N1 (vs. 1/7 in G1 NENs). Three (17%) cases were mixed exocrine/G3 NECs. After a median FU of 45 (up to 124) months, recurrence occurred in four G3 NEC (31%) patients (median disease-free survival 14 months) after an R0 PD. Disease-related survival was 93, 77 and 66% at 1, 3 and 5 years, respectively.Conclusion: Ampullary NENs are mostly G1-G2 neoplasms. Lymph node metastases rarely occur in G1 NENs < 2 cm in size, which may be treated with ampullectomy/excision. Survival is 66% 5 years after surgery. [ABSTRACT FROM AUTHOR]

The alpha-synuclein gene (SNCA) multiplication causes autosomal dominant Parkinson Disease (PD): triplication is associated with early-onset rapidly progressing parkinsonism with a strong likelihood of developing dementia, while duplication is associated with a less severe phenotype similar to idiopathic PD. We tested for SNCA multiplication 144 unrelated PD patients with a dominant family history. We identified one patient with SNCA duplication (0.7%). The SNCA-duplicated patient was a woman of 45 years of age with PD onset at 41 years of age. She experienced a rapidly progressive disease with early motor complications (on/off fluctuations and dyskinesias). Medical records confirmed that the proband's mother developed PD at 47 years of age and died at 63 with dementia. She experienced rapid progression in both motor and cognitive symptoms: development of dementia at 54 years of age, 7 years after onset. Although SNCA duplication is an unusual cause of familial PD testing for it is worthwhile. The clinical presentation of duplicated cases may be more aggressive than usual. [ABSTRACT FROM AUTHOR]

The antidiabetic drug metformin displays anticancer properties in several neoplasms. In pituitary NETs, aryl hydrocarbon receptor-interacting protein (AIP) is up-regulated by the somatostatin analog octreotide. Metformin inhibited QGP-1 cell proliferation in a dose- and time-dependent manner, at concentrations similar to those achievable in treated patients (−31 ± 12%, p < 0.05 vs basal at 100 μM). Moreover, metformin decreased pancreatic neuroendocrine tumors (PAN-NETs) cell proliferation (−62 ± 15%, p < 0.0001 vs basal at 10 mM), without any additive effect when combined with octreotide. Both octreotide and metformin induced AIP up-regulation. AIP silencing abolished the reduction of mTOR phosphorylation induced by metformin and octreotide. Moreover, metformin decreased HSP70, increased Zac1 and AhR expression; these effects were abolished in AIP silenced QGP-1 cells. In conclusion, metformin acts as an anticancer agent in PAN-NET cells, its activity is mediated by AIP and its interacting proteins. These findings provide a novel insight into the antitumorigenic mechanism of metformin. • Metformin acts as an anticancer agent in PAN-NET cells. • AIP interacts with HSP70, AHR and Zac1. • Metformin action is mediated by AIP and its interacting proteins. [ABSTRACT FROM AUTHOR]