Radiofrequency ablation combined with transarterial chemoembolization for liver metastases from gastrointestinal cancers.

Transarterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) has been reported to be effective for local control of different-sized hepatocellular carcinomas. However, it is unclear if these benefits could also be applicable to different-sized liver metastases from gastrointestinal cancers. The aim of this study was to evaluate the outcomes of TACE combined with RFA for liver metastases from gastrointestinal cancers. In this study, we retrospectively analyzed clinical data of 19 consecutive patients who had a total of 26 liver metastatic lesions from gastrointestinal cancers and underwent RFA followed by first-time TACE treatment. The tumor recurrence, overall survival rate and procedure-related complications were evaluated. Moreover, patients' demographics and tumor characteristics were analyzed to determine their impact on the outcomes. The technical success of TACE plus RFA was achieved with 2 major procedure-related complications found. The mean follow-up was 21.3 months. The total 1-, 2-, and 3-year survival rate was 89.4%, 52.6%, and 35.1%, respectively. It was found that the tumor size and the ratio of enhancement area were significant factors that influenced the overall survival. In conclusion, patients with gastrointestinal cancer-derived liver metastatic lesions of smaller size and larger enhancement area are considered appropriate candidates for TACE plus RFA.

Evaluation of 2 celecoxib derivatives: analgesic effect and selectivity to cyclooxygenase-2/1.

AIM: To evaluate the analgesic effects of 2 celecoxib derivatives and their inhibitory effects on cyclooxygenase (COX). METHODS: Four antinociceptive assays were used: the acetic acid-induced writhing test, hot plate test, hot tail-flick test and formalin test. Three doses were used in the analgesic assays and ED50 values were calculated. For the selectivity assay, macrophages were incubated with test compounds at various concentrations and then stimulated with calcimycin or lipopolysaccharide (LPS). The amounts of 6-keto-prostaglandin F1alpha(6-keto-PGF1alpha) and prostaglandin E2 (PGE2) in the supernatant were examined by radioimmunoassay (RIA). The selectivity of the test compounds was expressed as the IC(50,COX-1)/IC(50,COX-2) value. RESULTS: Celecoxib and its 2 derivatives had a significant analgesic effect. The ED50 values of celecoxib, PC-406 and PC-407 were 94.2, 67.9, and 63.3 mg/kg, respectively, for the acetic acid-induced writhing test; 104.7, 89.1, and 30.0 mg/kg, respectively, for the hot tail-flick response test; 60.7, 56.7, and 86.2 mg/kg, respectively, for the hot plate response test; 67.1, 55.8, and 68.8 mg/kg, respectively, for the formalin-induced response. That is, the ED50 of PC-406 was the lowest for the formalin and hot plate tests, which focus on changes above the spinal cord level; however, the ED50 of PC-407 was lowest for the tail-flick and writhing tests, which focus on changes at the spinal cord level. Celecoxib and PC-407 inhibited COX-1 with IC50 values of 39.8 and 27.5 nmol/L, respectively. PC-406 inhibited COX-1 with an IC50 value of more than 1000 nmol/L. The IC50 values for the effect of celecoxib, PC-406 and PC-407 on COX-2 were 4.8, 8.9, and 1.9 nmol/L respectively. The IC(50, COX-1)/IC(50,COX-2) ratios for celecoxib and PC-407 were 8.3 and 14.4, respec-tively. For PC-406, the ratio was greater than 112.2. CONCLUSION: Derivatives of celecoxib via substitution with an isopropyl or naphthyl group at the 5 position in the pyrazole ring still have analgesic effects and the ability to selectively inhibit COX-2. Substitution with a naphthyl group may have more effect on the peripheral pain pathway, whereas substitution with an isopropyl group may have more effect on the central pain pathway. This phenomenon occurs partly because substitution with an isopropyl group is more beneficial for COX-2 selectivity than is substitution with a naphthyl group.