Long-term results of the surgical management of insulinoma patients with MEN1: a Groupe d'étude des Tumeurs Endocrines (GTE) retrospective study.

OBJECTIVE: Management of insulinomas in the context of MEN1 remains poorly studied. The aim of this study was to evaluate long-term results of various surgical approaches in a large cohort of insulinoma-MEN1 patients. DESIGN AND METHODS: Consecutive insulinoma-MEN1 patients operated on for a nonmetastatic insulinoma between 1957 and 2010 were retrospectively selected from the MEN1 database of the French Endocrine Tumor Group. The type of surgery was categorized as distal pancreatectomy (DP), total pancreatectomy/cephalic duodenopancreatectomy (TP/CDP), or enucleation (E). Primary endpoint was time until recurrence of hypoglycemia after initial surgery. Secondary endpoints were post-operative complications. RESULTS: The study included 73 patients (median age=28 years). Surgical procedures were DP (n=46), TP/CDP (n=9), or E (n=18). After a median post-operative follow-up of 9.0 years (inter-quartile range (IQR): 2.5-16.5 years), 60/73 patients (82.2%) remained hypoglycemia free. E and TP/CDP were associated with a higher risk of recurrent hypoglycemia episodes (unadjusted hazard ratio: 6.18 ((95% CI: 1.54-24.8); P=0.010) for E vs DP and 9.51 ((95% CI: 1.85-48.8); P=0.007) for TP/CDP vs DP. After adjustment for International Union against Cancer pTNM classification, enucleation remained significantly associated with a higher probability of recurrence. Long-term complications had occurred in 20 (43.5%) patients with DP, five (55.6%) with TP/CDP, but in none of the patients who have undergone E (P=0.002). CONCLUSION: In the French Endocrine database, DP is associated with a lower risk for recurrent hypoglycemia episodes. Due to lower morbidity, E alone might be considered as an alternative.

Digestive calcitonin-secreting tumors of the foregut: comparison with non-calcitonin-secreting tumors.

OBJECTIVES: Digestive calcitonin-secreting endocrine tumors are very rare lesions of the foregut. This study was undertaken to compare the characteristics and the prognosis of these tumors and those of non-calcitonin-secreting endocrine tumors. METHODS: All patients with a digestive endocrine tumor of the foregut followed up in Reims University Hospital and whose serum calcitonin levels were determined between 1988 and 2004 were included. Clinical and tumor characteristics of calcitonin-positive and calcitonin-negative patients were compared. RESULTS: Thirty-two patients were included. Among the five (15.6%) with high calcitonin levels (median: 340 pg/ml, range: 42-7460 pg/ml), only one tumor was functioning (diarrhea). Significant differences between patients with positive and negative calcitonin levels were, respectively: liver metastases [5 (100%) versus 11 (40.7%); P=0.04], type according to the World Health Organization 2000 histological classification [notably 4 (80%) versus 3 (12.5%) poorly differentiated endocrine carcinomas; P=0.02] and Ki67 proliferation index [median: 25% (range: 20-30%) versus 7% (0-80%); P=0.03]. The only calcitonin-positive well-differentiated endocrine carcinoma had a high proliferation index (30%). Survival also differed significantly (P=0.001), as all calcitonin-positive patients died, with a median survival of 22.6 months (range: 1.2-27.2 months), versus five (18.5%) calcitonin-negative patients. Median follow-up period for the latter was 42.3 months (range: 3.4-208 months). CONCLUSIONS: The secretion of calcitonin appears predictive of a poor prognosis. Digestive endocrine calcitonin-secreting tumors correspond histopathologically to poorly differentiated or well-differentiated carcinomas with high proliferation indexes.

Prevalence, characteristics and prognosis of MEN 1-associated glucagonomas, VIPomas, and somatostatinomas: study from the GTE (Groupe des Tumeurs Endocrines) registry.

UNLABELLED: Few studies have concerned the rare functioning endocrine pancreatic tumors associated with multiple endocrine neoplasia type 1 (MEN 1). When sporadic, these tumors have a poor prognosis. AIM: To analyze the frequency, characteristics and prognosis of MEN 1-associated glucagonomas, VIPomas and somatostatinomas recorded in the GTE (Groupe des Tumeurs Endocrines) registry. METHODS: Records of the patients whose GTE registry codes included glucagonoma, VIPoma or somatostatinoma were reviewed. The diagnosis was confirmed when there were clinical signs of a functioning tumor and/or when blood levels of the peptide were higher than twice the upper limit of normal. RESULTS: Among 580 patients with MEN 1, duodeno-pancreatic involvement was present in 307 (52.9%). Five (1.6%) had a glucagonoma, 3 (0.98%) a VIPoma and 2 (0.65%) a somatostatinoma. A clinical syndrome was present in 1 patient with glucagonoma, in the 3 with VIPomas and in 1 with somatostatinoma. Tumor size was greater than 3 cm more often for these rare tumours (67%) than in patients with other type of duodeno-pancreatic involvement (28%) (P=0.02) and visceral metastases were more frequent (40% vs 15%; P=0.056). Ten-year survival of patients with glucagonomas, VIPomas or somatostatinomas (53.8%; CI95%: 15.5-92.1) was poorer than that of patients with insulinomas (91.4%; CI95%: 83.399.5; P=0.01) or gastrinomas (81.7%; CI95%: 74.9-88.5; P=0.20) and close to that of patients with non-functioning tumors (62.2%, CI95%: 41.0-83.9; NS). CONCLUSION: Glucagonomas, VIPomas and somatostatinomas, especially the functioning type, are very rare in patients with MEN 1. Prognosis is poor, probably because of large tumor size and high rate of metastasis. Survival is similar to that in patients with non-functioning tumors.