Somatostatin receptor expression in vivo and response to somatostatin analog therapy with or without other antineoplastic treatments in advanced medullary thyroid carcinoma.

The long-term treatment of metastatic medullary thyroid carcinoma (MTC) with somatostatin (SST) analogs was evaluated in 22 patients with persistant or relapsed disease and with in vivo positive SST receptor (SSTR) tumors. After surgical intervention all patients but one, initially or at a later time, had persistenly (15) or after relapse (7) elevated serum calcitonin (CT, 252-69482 pg/ml) and carcinoembryonic antigen (CEA, 8-1130 ng/ml) concentrations; also, all of them showed positive uptake in 111In-pentetreotide scanning. Daily doses of 0.4-1.0 mg octreotide subcutaneously, or monthly doses of 20-30 mg long-acting octreotide (LAR) intramuscularly for 3-21 months were administered. Systemic chemotherapy (Ch) with or without external radiotherapy (eRT) was given to 13 patients simultaneously. A beneficial effect on pre-existing diarrhea was observed in 8 patients (subjective partial remmission, sPR 36.4%); 10 other patients showed stable disease, while in 4 a worsening of pre-existing diarrhea was observed. CT and CEA concentrations decreased more than 25% in 4 out of 22 patients (18%) and 11 patients showed a decrease of less than 25% (biological SD). No objective response in tumour growth was demonstrated. Patients (10 survivors in group B) treated with Ch+eRT plus Octerotide showed higher sR (92.5%), lower mortality (23.1%), longer mean time to death (130 months) and longer mean total survival (mts) time (145 months) in comparison to group A patients who had 66.7% sR, 33.3% mortality, only 88.5 months mean time to death and 101 months mts-time. Long-term octreotide and octreotide-LAR treatment offers a subjective and biological partial remission in one third and in one fourth of the MTC patients respectively, but it does not improve the natural course of the tumor. It remains to be answered if these drugs, combined with other antineoplastic therapies, have a synergistic effect relating to treatment response and to patient survival and mortality.

Resistance to activated protein C and low levels of free protein S in Greek patients with inflammatory bowel disease.

OBJECTIVE: Patients with inflammatory bowel disease (IBD) frequently suffer from thromboembolic events. A recently identified mechanism for thrombophilia, the poor anticoagulant response to activated protein C, has been suggested as one of the leading risk factors for thrombosis. The aim of this study was to evaluate the frequency of thrombophilic abnormalities, including activated protein C-resistance (APCR), in Greek patients with ulcerative colitis (UC) and Crohn's disease (CD). METHODS: Forty-eight patients with UC, 36 with CD, and 61 matched healthy controls (HC) were studied. Cases with presence of lupus anticoagulant, use of anticoagulants or heparin, and pregnancy were excluded. Disease activity in CD was evaluated by use of the Crohns Disease Activity Index (CDAI) score and in UC by the Truelove-Witts grading system. Plasma levels of protein C, free protein S, antithrombin III (AT-III), activated protein C resistance (APCR), and fibrinogen were determined in IBD patients, as well as in HC. All the cases and controls with abnormal APCR were further studied by genetic testing for the factor V Leiden mutation. RESULTS: Mean fibrinogen levels in UC and CD patients were significantly elevated (p<0.0001), compared with HC. The mean values of free protein S, as well as mean APCR, were significantly lower in UC and CD patients than in the HC (p<0.0001). Seven (five UC and two CD) of 84 IBD patients (8.3%) and three of the HC (4.9%) had the factor V Leiden mutation. No significant difference was observed for the other thrombophilic parameters. Fibrinogen levels and profound free protein S deficiency were found related to disease activity. CONCLUSIONS: Thrombophilic defects are common in Greek patients with IBD and they could interfere either in the disease manifestation or in the thrombotic complications.