A non-insulin secreting malignant insulinoma of the pancreas.

We report a rare case of a non-insulin secreting malignant insulinoma of the pancreas and discuss its medical and surgical management. Surgical excision of malignant insulinoma produces good palliation and can increase survival.     

Effects of serial passage on the endocrine response and steroid metabolism of a rat mammary carcinoma.

A rat mammary carcinoma induced by 7-12 dimethylbenzanthracene was serially transplanted into successive generations of thymectomized host animals. After its 2nd passage, the growth of the tumour appeared hormone-dependent, regressing after oophorectomy and regrowing with administration of oestradiol 17 beta to the host. Third-generation transplanted tumours, however, showed only a transient regression after oophorectomy, and the growth of tumours after further passages appeared ovary-independent. Loss in hormone dependency was not accompanied by histological changes. There was however a progressive increase with successive transplantation in the ability of tumours to metabolize 7 alpha [3H] testosterone in vitro. This was accounted for by raised conversion to 5 alpha androstanediol.     

Effects of feeding partial and intermittent raw soya flour diets on the rat pancreas

Continuous administration of a diet consisting of raw soya flour produces pancreatic cancer in rats and sensitises the rat pancreas to the action of genotoxic carcinogens. We have therefore studied the effects of continuous feeding of diets containing lesser amounts of raw soya flour (5%, 25% and 50%) and feeding raw soya flour intermittently (2 days each week). The study has shown that a diet containing as little as 5% raw soya flour stimulates focal proliferation of the pancreatic acinar cells and sensitises to the action of azaserine. Similarly, intermittent feeding of raw soya flour induced focal proliferation of the acinar pancreas and, when 100% raw soya flour diet was fed for 2 days each week, resulted in the development of pancreatic cancer in some of the rats. We conclude that raw soya flour must be excluded from the diets of rats used in toxicological and carcinogenicity studies.     

An alteration of the endocrine pancreas involved in cancer

Tumor cells display hybrid metabolic features: some of their enzymes are phosphorylated as normally observed when catabolic hormones stimulate Gs-coupled receptors, whereas other enzymes adopt a configuration normally found in anabolic situations, mediated via tyrosine kinase receptors. Consequently, tumor cells have to rewire their metabolic pathways differently, whereas differentiated cells seem to respond preferentially to catabolic hormones. This gives mitotic cells a selective advantage since they deplete other cell reserves for their benefit. The pancreatic gamma aminobutyric acid selection switch between anabolism and catabolism explains the process, that is, a deficient release of gamma aminobutyric acid from beta cells leads to a concomitant release of catabolic glucagon and anabolic insulin and to a progressive desensitisation of insulin receptors on differentiated cells. New stem cells, with non-desensitised insulin receptors, respond to the dual anabolic and catabolic signals and rewire their metabolism in cancer mode. The aim of this letter was to discuss the causal pancreatic alteration of the anabolic–catabolic selection switch.     

Therapeutic effect of sunitinib malate and its influence on blood glucose concentrations in a patient with metastatic insulinoma

Standard cytotoxic chemotherapy has limited efficacy in advanced insulinomas, and control of blood glucose concentrations in these patients may be difficult. This article describes an elderly (74-year-old) man with metastatic insulinoma and severe hypoglycemia who was treated with repeated 6-week cycles of oral sunitinib malate (25 mg/day for 4 weeks, followed by 2 weeks off treatment). After treatment for more than 2 years, his condition improved and he continued to have a good quality of life with no evidence of tumor progression based on PET/CT findings. Although sunitinib treatment lowered the patient’s blood glucose concentrations further and induced repeated symptomatic hypoglycemic episodes, he was able to tolerate the treatment well after changing the timing of sunitinib dosing and adjusting his diet.     

Localization of endocrine tumors of the pancreas with endoscopic ultrasonography

High-frequency endoscopic ultrasonography (EUS) was used to image the pancreas through the wall of the stomach and duodenum in 12 patients with clinically suspected pancreatic endocrine tumors. In another patient, endocrine tumors in the wall of the duodenum were imaged by EUS. The findings were compared with those obtained by dynamic computed tomography (all patients) and selective angiography (eight patients). Laparotomy was done in eight patients. In our 13 patients, EUS detected endocrine tumors of the pancreas and duodenum in ten patients. More than one tumor was evident in five patients, including one of two patients with multiple endocrine neoplasia syndrome type I. In the eight patients treated surgically, there was one false-positive finding as a result of hypertrophic peripancreatic lymph nodes and one false-negative finding, in retrospect obviously imaged but incorrectly interpreted. The technique of EUS imaged small tumors in the pancreas (0.5 to 2.0 cm in diameter) in five patients where dynamic computed tomography and selective angiography were negative, but surgery and pathologic examination confirmed the EUS findings. This technique appears to be an important new addition to the battery of tests used for preoperative localization of endocrine tumors of the pancreas.     

Water-electrolyte homeostasis and hemostasis system after transurethral resection of the prostate

Changes in coagulogram and water-electrolyte homeostasis were studied in 89 patients surgically treated for prostatic adenoma (TUR). The patients were divided into 2 groups: group 1 (n=21) was operated with use of distilled water, group 2--with 5% glucose solution. The following examinations were made in all the patients: extended coagulogram, total blood count, concentration of electrolytes, creatinin, plasma urea and glucose, osmolality measurements. These were made thrice: before the operation, on postoperative day 1, postoperative day 3. Postoperative changes of hemostasis and water-electrolyte homeostasis of plasma were less significant in group 2. The risk of postoperative hemorrhage is higher in patients of group 1.     

The effect of ionizing radiation on the primate pancreas: An endocrine and morphologic study

In this study we evaluated the endocrine, biochemical, and haematological derangements as well as pancreatic and histological changes of the bone-marrow in the primate following external fractionated subtotal marrow irradiation without bonemarrow reconstitution. The irradiation was administered in preparation for pancreatic transplantation. Two groups of animals (ten in each group) received 800 rad (8 Gy) and 1,000 rad (10 Gy) respectively over 4 to 5 weeks. A maximum of 200 rads (2 Gy) were administered weekly as photons from a 6 MV linear accelerator. During irradiation the animals remained normoglycaemic in the presence of transiently elevated liver enzymes and serum amylase values, which returned to normal on completion of the irradiation. Insulin release was significantly reduced in both groups during irradiation and was associated with minimally decreased K-values in the presence of mild glucose intolerance. Pancreatic light morphologic changes included structural changes of both exocrine and endocrine elements and included necrosis of the islet cells and acinar tissue. Islet histology demonstrated striking cytocavitary network changes of alpha and beta cells, including degranulation, vacuolization, mitochondrial destruction, and an increase in lysosomes. A hypoplastic bonemarrow ranging from moderate to severe was observed in all irradiated recipients. Near total fractionated body irradiation in the primate is therefore associated with elevated liver enzymes, pancytopenia, transient hyperamylasaemia, hypoinsulinaemia, a varying degree of pancreatitis, and bonemarrow hypoplasia.     

Effects of amifostine on radiation-induced cardiac damage

The purpose of this study was to investigate whether administration of amifostine prior to irradiation could reduce radiation damage of the rat heart. Female Spraque-Dawley rats were randomized to receive single-dose irradiation (0-22.5 Gy) locally to the heart. Fifteen to twenty minutes before radiation exposure, the animals received either intraperitoneally administered amifostine (160 mg/kg) or buffered saline solution. At 6 months post-irradiation, cardiac function was assessed by the in vitro working rat heart preparation. The severity of interstitial and/or perivascular fibrosis in different anatomical regions of the rat heart was assessed using a semi-quantitative scoring system. Radiation exposure to doses ≥20 Gy markedly reduced coronary flow, aortic flow and cardiac output. Administration of amifostine prior to radiotherapy afforded protection against these effects and normal cardiac output was maintained, even after 22.5 Gy. A small, non-significant, reduction in histological damage (i.e. perivascular fibrosis and interstitial fibrosis) was also apparent in animals treated with amifostine. There was a clear protective effect of amifostine on the severity and extent of macroscopic damage in lung tissue included in the cardiac irradiation field. The findings of this study suggest that a single dose of amifostine administered prior to irradiation is effective in reducing cardiac damage.