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Abstract.: Methods: The Japanese version (version 1.2) of the UCLA PCI was developed through a process of translation, back-translation, and refinement after interviewing patients. Reliability and validity were examined for 125 Japanese patients with localized prostate cancer. The patients simultaneously responded to the Japanese version of the RAND 36-Item Health Survey (SF-36) and five representative questions from the International Index of Erectile Function (IIEF). Results: Internal consistency reliability was very high for both urinary and sexual function scales, and lower for bowel function. The test-retest reliability of the urinary and sexual function scales and the urinary bother scales was stable, while that of the bowel function and bother scales was relatively unstable. Sexual function scores did not correlate highly with sexual bother scores. Furthermore, poor sexual function and bother had little association with the SF-36 scores. Missing data as to urinary and bowel function/bother scales were minimal (0.8%–2.4%), while those for sexual function and bother were relatively high (4.8%–11.2%). Conclusions: The results of this pilot study, together with the previous American study, suggest ethnic or cultural difference in how impaired sexual function is integrated into overall QOL. A future cross-cultural comparative study using the UCLA PCI and SF-36 will provide useful information about the influence of cultural or ethnic differences on health-related QOL in prostate cancer patients.

Objectives:The expression of p21WAF–1/CIP–1, a downstream regulator of p53, is a universal cycline–dependent kinase inhibitor. The aim of this study is to determine whether p21 expression could be used as a prognostic marker in urothelial carcinomas.Methods:By use of immunohistochemistry, we examined the expression of p21WAF–1/CIP–1 in 60 patients with urothelial carcinomas and compared the results with the status of nuclear p53 and mdm2 accumulation, expression of type IV collagen in the basement membranes and upregulation of metalloproteinases (MMP–1, MMP–2, MMP–9).Results:p21WAF–1/CIP–1 immunoreactivity was observed in 51.7% of the tumors, and in only 39% of the tumors with functional p53 loss (nuclear accumulation of p53 and/or mdm2). p21WAF–1/CIP–1 overexpression was not associated with grade and stage of the tumors and presence or absence of concomitant CIS. Moreover, p21WAF–1/CIP–1 overexpression was not associated with upregulation of metalloproteinases or destruction of type IV collagen of basement membranes.Conclusions:Our results suggest that p21WAF–1/CIP–1 expression is regulated by both p53–dependent and independent pathways and is not related to grade, stage or potential markers of invasion in urothelial carcinomas.

Purpose: Expression levels of the multidrug-resistance (mdr1), multidrug resistance-associated protein (MRP), glutathione-S-transferase-pi (GST-pi) and DNA topoisomerase II (Topo II) genes in normal kidney and renal cell carcinomas were analyzed to study the complexity of the roles of these genes. Materials and Methods: The reverse transcription-polymerase chain reaction (RT-PCR) assay was used with beta"2 microglobulin (beta"2 m) as the internal control. Results: In normal kidneys, the expression levels of the 4 genes in individual normal kidney samples correlated significantly with one another. Comparisons of the expression levels between normal kidneys and renal cell carcinomas showed that only the mean MRP gene expression level was higher in renal cell carcinomas than in normal kidneys (p = 0.018). The expression patterns of the 4 genes in renal cell carcinomas differed markedly for nonpapillary and papillary tumors. The mean MRP/beta"2 m ratio for the papillary type was significantly lower than that for the nonpapillary alveolar type carcinoma (p = 0.004). The 4 genes showed moderate positive correlations with one another in alveolar type renal carcinoma similar to the correlations observed in normal kidneys. In contrast, in papillary type, MRP expression was inversely correlated with mdr1 and Topo II expression. Conclusion: Differences in cytogenetic changes, origins and natural histories between papillary and nonpapillary carcinoma may be associated with these distinct expression patterns of the resistance-related genes. Further study is required to clarify whether the differences in the expression patterns between these 2 structural types of carcinoma affect their chemosensitivities and clinical outcomes.

The role of the renin-angiotensin system in blood pressure control and in the development of hypertension was investigated by generating transgenic mice carrying the rat renin or angiotensinogen gene or both genes under the control of the mouse metallothionein I promoter. The systolic blood pressure was significantly elevated in transgenic mice carrying both transgenes but was maintained normally in those bearing either of the transgenes. The transgene was effectively and properly transcribed to form the mature mRNA in the transgenic mice. The production of rat renin and angiotensinogen in the transgenic mice carrying the corresponding transgene was also verified by immunoanalyses of these proteins. Furthermore, the specific angiotensin-converting enzyme inhibitor captopril was effective in reducing the elevated blood pressure of the hypertensive transgenic mice. These results indicate that the combined action of the exogenous rat renin and angiotensinogen is responsible and necessary for elevation of blood pressure in the hypertensive transgenic mice.

P-glycoprotein modulators are respected to be multidrug resistance reversing agents in cancer chemotherapy. Some calcium channel blockers, calmodulin inhibitors or immunosuppressive agents have been used in clinical studies, although the dose of these drugs required to test in vitro experimental data might cause potent pharmacological effects which are not desirable in patients. By using LLC-GA5-COL150 cells that express P-glycoprotein specifically on the apical membranes, we examined the transport of anticancer drugs mediated by P-glycoprotein. Cepharanthin, a biscoclaurine alkaloid, potently inhibits the transport of vinblastine and daunorubicin, both commonly used anticancer agents. The 50% inhibitory concentration of cepharanthin on daunorubicin transport was 2.06 microM. Combined inhibitory effects on daunorubicin transport were observed when cepharanthin was used together with cyclosporin A, a potent immunosuppressive agent and P-glycoprotein modulator. Cepharanthin itself was transported by P-glycoprotein. Transcellular transport of cepharanthin across LLC-GA5-COL150 cell monolayers was saturable when its concentration was under 5 microM, and the transport was inhibited by P-glycoprotein modulators. These results indicate that cepharanthin can reverse multidrug resistance, and proper combination with other P-glycoprotein modulators could potentiate its inhibitory effect on expelling the anticancer drugs out of the cell via P-glycoprotein.

We report for the first time the frequency distributions of HLA-DRB1 and -DQB1 genes in 55 patients with testicular germ cell carcinoma (TGC) using the modified PCR-RFLP method and compare the results with those for 1216 healthy Japanese control subjects. The modified PCR-RFLP method produced accurate, reproducible cleavage patterns that are easily discriminated. HLA-DRB1*0410 was the susceptibility allele (RR = 3.26, P = 0.006) and DQB1*0602 appears to be a candidate protective allele (RR = 0.26, P = 0.02) for TGC in the Japanese. None of the HLA-DRB1 and -DQB1 alleles showed a specific tendency for histological type or clinical stage of the tumours. Previous studies based on serotyping methods failed to show these allelic associations. High-resolution genotyping is essential because the peptide-binding domain of MHC class II molecules is determined more precisely by their genotypes than by their serotypes. In addition, inherent technical difficulties and typing errors of up to 25% make serotyping inefficient. Our results suggest that high-resolution genotyping is a useful genetic marker to determine risk for TGC.

Purpose: Although urinary calculi have been frequent late complications of the Kock continent urinary diversion, they have not been regarded as significant problems in patients with the Indiana pouch because of the lack of foreign material present. However, stones developed in a significant percentage of our patients with an Indiana pouch. We investigated the characteristics of stone formation in patients with the Indiana pouch and compared them to those with a Kock pouch. Materials and Methods: Detailed clinical courses regarding stone formation were reviewed in 72 patients with a Kock pouch and 54 with an Indiana pouch who had a minimum followup of 12 months. Results: Stones developed in 7 of 54 patients (12.9 percent) with an Indiana pouch compared to 31 of 72 (43.1 percent) with a Kock pouch. The incidence gradually increased with longer followup but it was lower in the Indiana than in the Kock pouch group (5-year stone-free rate 84 percent versus 66 percent, respectively). Although the stones consisted principally of a mixture of struvite, carbonate apatite and ammonium hydrogen urate, variable amounts of calcium oxalate were identified in 50 percent of the Indiana pouch calculi. Conclusions: Not only urinary infections but also metabolic factors were considered to be involved in stone formation within the Indiana pouch. However, the substantially higher rate of stone formation in our Kock and Indiana pouch groups than has been reported in the United States suggested that no or infrequent pouch irrigations in our patients were important risk factors for urinary calculi.

Laparoscopic surgery has become a common modality in the urological field. However, a relatively high incidence of complications was reported due to the complexity of the laparoscopic approach. Herein we report the first case of retroperitoneal chylocoele following laparoscopic adrenalectomy.