9 Since Albright’s novel statement in 1941 about the humoral nature of tumor hypercalcemia,10 many efforts have been made to prove the secretion of either ectopic PTH

or a substance that has functional similarity to PTH. The enthusiasm and the ensuing hard work led to the discovery of PTHrP in 1988,11 which was a turning point in the correct Z-VAD-FMK chemical structure interpretation of tumor hypercalcemia.12 In an extensive review of the literature we could find 42 patients with pancreatic NET and hypercalcemia. Clinical and laboratory data of the reviewed cases as well as the present case are shown in table 1. The patients are 20 men and 22 women with a mean age of 45 years (age range 8-77 years). Inhibitors,research,lifescience,medical The largest size of the tumor was 3.9-18 cm with a mean of 10.2 cm. All patients were hypercalcemic with serum calcium concentrations ranging from 10.6-26.4 mg/dl with a mean of 15.5 mg/dl. Serum concentrations Inhibitors,research,lifescience,medical of PTH were low or undetectable in 31 cases, and within normal range in 11 cases. Of 25 patients whose serum PTHrP had been measured, 24 had elevated levels ranging from 2.3-40 pmol/L with a mean of 10.8 pmol/L, which was about 10 times the upper limit of normal range. Data for IHC, available for 17 patients, showed positivity for PTHrP in all except for two cases.13 chromogranin

(CgA), synaptophysin (Syn), neuron specific enolase (NSE), somatostatin (So) and calcitonin (Cal) were Inhibitors,research,lifescience,medical positive in varying combinations in all cases except two.14 Moreover, KI 67 in those who were analyzed was less than 10%, which was in agreement with the low growth rate and Inhibitors,research,lifescience,medical long survival of those patients. Table1 Clinical and laboratory data of 42 patients with pancreatic neuroendocrine tumor and hypercalcemia Surgical removal of the tumor was the main therapeutic option. However, complete removal of the tumor could be done in only seven cases because of multiple liver metastasis, local invasion and hypervascularity of the tumors. Indeed multiple liver metastases were seen in 80 % of the patients. Inhibitors,research,lifescience,medical In these cases, distal pancreatectomy and/or debulking were done. Due to such limitations

for surgery, nonsurgical treatment modalities are of utmost significance. Somatostatin analogues have been used in patients with NET for the last two decades. Their alleviating effects on hypercalcemia as well as their potential anti tumor effects have also been reported. In last couple of years, Sandostatin LAR or similar analogues have been much used in almost all cases in which complete surgical removal of the tumor has been impossible. It should be noted that anti proliferative effects of the drug is weak, and in some cases the tumor has progressed with time.15,16 Interferon α is another biotherapeutic agent approved for patients with NET. A previous study,16 reported that it was effective in reducing serum calcium and maintaining normocalcemia for a period of six months.