In patients with postprandial and/or fasting neuroglycopenia NIPHS may be suspected when insulin levels are low but inadequately suppressed and localization studies failed to show a distinct pancreatic tumor.

The rarity of malignant insulinoma limits reports on therapeutic strategies and outcome. The treatment and follow-up of 10 patients, all presenting an insulinoma with metastatic disease of the liver and newly diagnosed between 1992 and 2002, is reported. Pancreatic surgery with successful removal of the primary tumor preferentially located in the tail was performed in 7 women and 3 men, median age 55 years (range 36-82 years). If appropriate, 5 patients underwent additional hepatic surgery and lymph node resections. Liver metastases as the major cause of postoperatively persistent hypoglycemia were subsequently treated by repeated transarterial hepatic chemoembolization and chemoperfusion protocols using high-dose transhepatic streptozocin perfusions (3-4 g per session). The current median survival time for all 10 patients is 2.6 years (range: 1.6-9.7 years). Six patients are currently alive with a median survival of 3.7 years (1.7-9.7 years), five of them with stable disease and free of hypoglycemia. Four patients died after a median survival of 1.8 years (range: 1.6-7.5 years) from complications of unmanageable hypoglycemia. It is concluded that the necessity to treat debiliating and life-threatening hypoglycemia in metastatic malignant insulinoma warrants the option of radical endocrine surgery in combination with extended and repeated postoperative chemoembolization of liver metastases.

Clinical and molecular studies have implicated epidermal growth factor receptor (EGFR), insulin-like growth factor (IGF) and target of rapamycin (mTOR) signaling pathways in the regulation of pancreatic neuroendocrine tumor (PanNET) growth. Interpretation and comparison of these studies is complex due to clinical and molecular tumor heterogeneity. We therefore focused in this study on insulinomas, which we examined for mRNA and protein expression of EGFR, IGF and mTOR signaling pathway components by quantitative real-time PCR (n=48) and immunohistochemistry (n=86). Findings were compared with normal pancreatic islets and correlated with histopathological data and clinical outcome. Insulinomas showed low EGFR and high IGF2 expression. IGFBP2, IGFBP3 and IGFBP6 mRNA levels were 2-4 folds higher than in islets. High protein expression of IGF2, IGF1R and INSR (in 51-92% of the tumors) and low to moderate expression of mTORC1 pathway proteins p-PS6k and p-4EBP1 (7-28% of the tumors) were observed. Correlations were found between 1) ERK1 mRNA expression and that of numerous IGF pathway genes, 2) p-ERK and IGF1R protein expression and 3) decrease of IGF pathway components and both metastatic disease and shorter 10 years disease free survival. In conclusion, our observations suggest that high expression of IGF signaling pathway components is a hallmark of insulinomas, but does not necessarily lead to increased mTOR signaling. Reduced expression of IGF pathway components may be an adverse prognostic factor in insulinomas.

Background In patients with insulinoma, biochemical proof of inappropriately elevated insulin secretion during hypoglycemia is required prior to surgery. Because circulating insulin levels usually vary widely, we have used the combined OGTT-fasting test to define new normative criteria for a retrospective systematic analysis. Methods We retrospectively analyzed insulin concentrations from OGTT-fasting tests of 64 patients with surgically removed insulinomas. In addition, the response to intravenous somatostatin infusions was estimated. Normative criteria were defined to obtain comparable estimates of insulin concentrations: basal, glucose-stimulated maximum, postglucose plateau, and secretory bursts. Results Three types of insulin secretion patterns were identified: (1) the autonomous secretion pattern (type 1, N = 17) with basal and post-OGTT plateau insulin concentrations of approximately 50 mU/L, suppression after OGTT by 41%, virtual absence of distinctive secretory bursts, and resistance to somatostatin-mediated suppression (25 %); (2) the inadequate suppression pattern (type 2, N = 28) with moderately elevated basal and post-OGTT insulin concentrations of approximately 20 mU/L, suppression after OGTT by 73%, absence of secretory bursts, and incomplete somatostatin-induced suppression (56 %); (3) the late-burst secretion pattern (type 3, N = 19) with similar basal and post-OGTT insulin concentrations of 17 mU/L, suppression after OGTT by 76%, true insulin bursts of D 13 ± 11 mU/L (184%), and nearly complete somatostatininduced suppression by 64%. Conclusions By means of a new normative analysis of the combined OGTT-fasting test, three different patterns of insulin secretion can be described in patients with insulinoma: the autonomous secretion type, the inadequate suppression type, and the late-burst secretion type.

This case report deals with a 79-year-old patient with a gastrointestinal stromal tumor (GIST) of the anterior rectal wall which was unusually located between the rectum and the prostate gland. In addition, this patient suffered from subvesical obstruction accompanied by an elevated PSA level. These circumstances led to our decision to operate on the tumor via simultaneous radical retropubic prostatectomy. In our opinion this resection technique was easier and less traumatic for the patient compared to procedures performed via the abdomen and perineum. This case report demonstrates that in the case of tumors located between the rectum and the prostate gland the differential diagnosis should include not only prostate carcinoma but also rare tumor entities such as GIST.