Clinical characteristics and management of insulin-producing neuroendocrine carcinomas.

BACKGROUND AND AIMS: Due to rarity of insulin-producing pancreatic neuroendocrine carcinomas, no large, nor randomized studies of the clinical course, treatment options and outcome are available. Therefore, we want to share our personal experience and we retrospectively reviewed a cohort of five patients. PATIENTS AND METHODS: This study reports on the clinical characteristics, disease course, management and outcome of five patients with an advanced pancreatic neuroendocrine carcinoma with insulin production, which we followed recently in our center (between 2006 and 2015). Extraordinary for our cohort is that, except for one patient, which was diagnosed with a de novo malignant insulinoma, all other patients were diagnosed with a non-functional pancreatic neuroendocrine tumor which evolved during the disease course to a malignant insulinoma. RESULTS: Although various treatment strategies, both surgical and medical, are used to prolong survival and prevent hypoglycemic events, long-term prognosis of these patients remains poor, especially after transformation of a non-functional pancreatic neuroendocrine tumor to an insulin-producing neuroendocrine carcinoma. Of all five patients, only one is still alive, the other four died 25, 17, 3 and 1 month(s) after diagnosis of the malignant insulinoma. In general, prognosis is determined by early diagnosis and treatment, and by resectability of the tumor and its biological behavior. CONCLUSION: Management of a malignant insulinoma is very challenging and a better understanding of the underlying mechanisms of this disease entity and its biological behavior is absolutely necessary to improve diagnostic tools, treatment and outcome in the future. (Acta gastro-enterol. belg., 2016, 79, 321-327).

Fructose consumption impairs serotonergic signaling in the murine enteric nervous system.

The intake of free fructose has increased substantially since the development of high-fructose corn syrup. This has not only been associated with metabolic disorders but recent evidence also indicates that chronic fructose consumption can affect neuronal and cognitive function. In this study we investigated the effects of fructose consumption on serotonergic signaling and neuronal activity in the mouse submucous plexus. Male mice were put on a control or fructose (23% solution) diet for 6 weeks or were assigned to a recovery group that received normal water (2 weeks) after 4 weeks of fructose. At the end of the diet, gene expressions and enteric neuronal activity, after depolarization with high K(+) and 5-HT, were measured using Ca(2+) imaging and RT-qPCR, respectively. Even in the lack of gain weight and the absence of changes in duodenal permeability, the total number of 5-HT-responding neurons and the depolarization and 5-HT-evoked Ca(2+) amplitudes were significantly lower after fructose consumption. Expression of synaptobrevin CaV 2.1 and CaV 2.2 mRNA did not differ after fructose intake; however, CaV 2.1 mRNA levels were significantly higher in the recovery animals. SERT mRNA concentration, isolated from submucosal plexus containing mucosal epithelium, was significantly decreased after fructose consumption. Chronic fructose consumption impairs serotonergic signaling in the mouse submucous plexus, prior to weight gain and detectable intestinal permeability problems.