Reduced perioperative immune response in video-assisted versus open surgery in a rat model.

PURPOSE: To establish the best technique for thoracoscopic pneumonectomy in the rat and to analyze the differences in perioperative immune response between open and video-assisted thoracoscopic surgery (VATS) in a rat model. METHODS: The four experimental groups studied were as follows: VATS pneumonectomy, open pneumonectomy, thoracoscopic observation, and open observation. We measured the immunocyte counts and serum cytokine levels postoperatively in each group. RESULTS: The CD3+, CD4+, and CD8+ lymphocyte counts were decreased significantly 12-24 h postoperatively in all groups. Immunosuppression peaked later in the open approach groups than in the VATS groups. The interleukin-6 level was significantly higher in the open approach groups than in the VATS groups. CONCLUSIONS: From the viewpoint of immunity, in this rat model VATS was less invasive than open surgery, and open surgery caused greater immunosuppression than VATS, irrespective of organ resection.

Prognostic significance of p16(INK4a) hypermethylation in non-small cell lung cancer is evident by quantitative DNA methylation analysis.

BACKGROUND: p16(INK4a) is a tumor suppressor gene frequently inactivated by aberrant promoter hypermethylation. In the present study, p16(INK4a) methylation was evaluated in non-small cell lung cancer (NSCLC) using a quantitative assay and the clinical significance of the methylation was explored. MATERIALS AND METHODS: A total of 244 tumor samples from formalin-fixed paraffin-embedded archives were examined in this study. p16(INK4a) methylation was analyzed by the fluorescence-based, real-time methylation-specific PCR assay, MethyLight. The quantitative methylation value was expressed as the percentage of methylated reference (PMR). RESULTS: The median level of p16(INK4) methylation was 0.55 PMR (range 0.00-503.4). The p16(INK4) methylation value was significantly higher in males (p = 0.005) and in squamous cell carcinoma (p = 0.018). Prognostic analysis using the Cox proportional hazard model showed that the p16(INK4a) methylation value was a significant prognostic factor (odds ratio, 1.005; 95% CI, 1.003 to 1.008; p < 0.0001). The p16(INK4a) methylation value remained a significant prognostic factor (p = 0.0004) in multivariate analysis including age, gender, histological type and clinical stage. Specimens were then classified into hypermethylated or non-hypermethylated groups based on the p16(INK4a) methylation value using various cut-offs from 1 to 100 PMR. There was no significant difference in prognosis between the two groups using a cut-off value of 1 PMR. On the other hand, there was a significant difference using 6 PMR or more as the cut-off value (p < 0.01). CONCLUSION: These results provide clear evidence for the prognostic significance of p16(INK4a) methylation in NSCLC using quantitative DNA methylation analysis. Careful assessment of DNA methylation is needed because qualitative methylation analysis may overestimate low levels of methylation, which have less clinical significance.

Prognostic significance of the polymorphisms in thymidylate synthase and methylenetetrahydrofolate reductase gene in lung cancer.

BACKGROUND: Thymidylate synthase (TS) and methylenetetrahydrofolate reductase (MTHFR) play important roles in folate metabolism. Previous studies have suggested that TS expression is a prognostic factor in non-small cell lung cancer (NSCLC). The TS gene has a variable number of tandem repeats (VNTR) and single nucleotide polymorphism (SNP) in the 5'-untranslated region, which are associated with TS expression. This association suggests that the TS polymorphism is a novel prognostic factor in NSCLC. In the present study, multiple genetic polymorphisms, TS VNTR, TS SNP and MTHFR C677T, were analyzed in NSCLC and compared with clinicopathological features and patients' prognoses. MATERIALS AND METHODS: Genomic DNA was isolated from 294 surgically resected NSCLC tissues. The genotypes were determined by PCR and PCR-RFLP. The TS VNTR and SNP were combined, followed by functional stratification of H/H (3G/3G), H/L (2R/3G, 3G/3C) and L/L (2R/2R, 2R/3C, 3C/3C). Patients' prognoses were compared with TS and/or MTHFR genotype groups. TS was divided into the H- (H/H, H/L) and L-groups (L/L) according to functional stratification and MTHFR C677T was divided into C- (C/C) and T-groups (C/T, T/T). RESULTS: TS VNTR, the SNP and the TS functional type, along with MTHFR C677T, showed no significant association with clinicopathological factors. There were no differences in prognosis between each genotype or functional group when the TS and MTHFR groups were considered separately. However, we found a unique association between prognosis and the TS functional group in stage I NSCLC, taking both TS and MTHFR groups into consideration. The patients in the TS L-group survived longer than those in the H-group when limited to stage I and MTHFR C-group (p = 0.086). This relationship between the TS genotype group and prognosis was statistically significant in the subgroup of stage IB and MTHFR C-group (p = 0.030). In contrast, the patients in the TS H-group survived longer than those in the L-group when limited to stage I and MTHFR T-group (p = 0.052). CONCLUSION: The TS and MTHFR genotypes can be prognostic factors in NSCLC, where gene-gene interactions between the genotypes may occur. Further validation and investigation of the involvement of genotypes of folate metabolizing enzymes in the prognosis of NSCLC patients are required.

Efficacy of Stronger Neo-Minophagen C compared between two doses administered three times a week on patients with chronic viral hepatitis.

BACKGROUND: A daily injection of glycyrrhizin (Stronger Neo-Minophagen C (SNMC) containing 40 mg glycyrrhizin in a 20 mL ampoule) lowers alanine aminotransferase (ALT) levels in patients with chronic viral hepatitis. METHODS: The therapeutic effects of intermittent administration of SNMC three times a week for 12 weeks were evaluated and compared between two doses (40 and 100 mL) in a randomized clinical trial. RESULTS: Overall, the therapeutic response was better in the 53 patients allocated 100 mL than the 59 who were allocated to have 40 mL SNMC (P = 0.0243). At the completion of SNMC treatment, ALT levels decreased more extensively in the patients on 100 mL than those on 40 mL SNMC (-29 vs-50% in comparison with the baseline value, P = 0.0002). Minor side-effects occurred in both the patients on 100 mL (20%) and those on 40 mL (12%), but they did not require any therapies. CONCLUSIONS: Intermittent SNMC would be efficient in suppressing ALT levels in patients with chronic viral hepatitis in a dose-dependent manner. Taken along with infrequent and very mild side-effects, long-term intermittent SNMC would benefit patients with chronic hepatitis by maintaining their quality of life with easier compliance.