CRYOTHERAPY OF HEPATIC METASTASES AND REGIONAL PERFUSION WITH LOW-DOSE STREPTOZOTOCIN IN THE MANAGEMENT OF METASTATIC MALIGNANT INSULINOMA

A 67-year-old man with intractable hypoglycaemia due to a malignant pa ncreatic insulinoma with multiple hepatic metastases is reported. Cont inuous intravenous infusion of dextrose was necessary to prevent life- threatening hypoglycaemia; high-dose parenteral octreotide was ineffec tive and oral diazoxide was associated with intolerable gastrointestin al side-effects. Preoperative imaging failed to identify the primary t umour with certainty. At laparotomy, the tumour was located in the pan creas and excised. Intraoperative cryotherapy was administered to hepa tic metastases inducing localised ice-ball formation and subsequent ne crosis of the lesions. These interventions led to prompt resolution of the hypoglycaemia with normalisation of plasma concentrations of isle t B-cell products. In an effort to consolidate the beneficial effects of surgery, chemotherapy was instituted post-operatively using the isl et B-cell toxin streptozotocin. In an innovative therapeutic approach, the drug was infused via the hepatic artery for 5 consecutive days at a reduced dose calculated to induce an insulitis in the residual hepa tic metastases analogous to that described in murine models of diabete s. The chemotherapy was well tolerated although the course of treatmen t was curtailed by problems with catheter placement. Nonetheless, the patient has, to date, remained well and free from hypoglycaemia during more than 3 years of follow-up. These therapeutic strategies appear t o merit further evaluation.