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Objectives To determine the significance of molecular diagnosis of lymph node metastasis using quantitative reverse transcription polymerase chain reaction in patients with upper urinary tract urothelial cancer. Methods A total of 51 patients with upper urinary tract urothelial cancer who underwent extended lymphadenectomy were included in the present study. Retrieved lymph nodes from each patient were divided into two parts. One part was assessed by quantitative reverse transcription polymerase chain reaction assay for molecular staging, whereas the other one was assessed by routine histopathological examination. Four kinds of molecules (FXYD3, KRT19, KRT20 and UPK2) were selected as markers to detect urothelial cancer cells. Results The average number of retrieved lymph nodes was 18.3. As UPK2 showed the best discrimination ability among four markers, the patients were classified in three categories according to UPK2 expression: N(+)PCR(+) for patients who had lymph node metastasis by routine pathological diagnosis as well as quantitative reverse transcription polymerase chain reaction (n = 4); N(−)PCR(+) for patients who had lymph node metastasis by polymerase chain reaction but not by routine pathological diagnosis (n = 7); and N(−)PCR(−) for patients who showed no lymph node metastasis not only by routine pathological diagnosis but also by polymerase chain reaction (n = 40). The prognosis of the N(−)PCR(+) group was better than that of the N(+)PCR(+) group, and similar to that of the N(−)PCR(−) group. Conclusions Quantitative reverse transcription polymerase chain reaction could detect micrometastasis in patients with upper urinary tract urothelial cancer. However, the prognosis of patients with micrometastasis is better than patients with pathologically metastasized lymph nodes, and similar to patients without micrometastasis.

Objectives To identify biomarkers predicting prognosis in bladder cancer patients undergoing the gemcitabine and cisplatin regimen. Methods We studied 52 patients with metastatic bladder cancer treated with the gemcitabine and cisplatin regimen by evaluating the relationship between the expression of two biomarkers, ribonucleotide reductase subunit M1 and excision repair cross complementing 1, by immunohistochemistry and clinical outcomes. Results The patients with low expression of ribonucleotide reductase subunit M1 showed a higher objective response rate by the gemcitabine and cisplatin regimen than those with high expression of ribonucleotide reductase subunit M1 (80.0% and 45.5%, respectively). No differences were observed according to the expression level of excision repair cross complementing 1. Low expression of ribonucleotide reductase subunit M1 significantly prolonged overall survival and progression-free survival compared with the high expression group. Low expression of excision repair cross complementing 1 tended to prolong overall survival and progression-free survival, but there were no significant differences (P = 0.07 and 0.10, respectively). Multivariate analysis showed that the expression of ribonucleotide reductase subunit M1 was the only independent prognostic factor (P = 0.012). Conclusions The expressions of ribonucleotide reductase subunit M1 seem to be associated with clinical response and survival in patients with metastatic bladder cancer treated with gemcitabine and cisplatin-based chemotherapy.

Objectives To investigate the effect of weight loss intervention on the urinary stone risk parameters in a rat model of metabolic syndrome. Methods In a prevention study, 4-week-old male Otsuka Long-Evans Tokushima “Fatty” rats were randomly assigned to three groups: control, food-restricted and food-restricted + exercise-trained groups. In a treatment study, 24-week-old male Otsuka Long-Evans Tokushima “Fatty” rats that had already developed type 2 diabetes were randomly assigned to the same three groups. Blood and 24-h urine chemistry were measured after 16 weeks. Results In both studies, food-restricted and food-restricted + exercise-trained rats showed significantly higher urinary pH and higher excretion of urinary citrate than control rats. In the prevention study, ion-activity products of calcium oxalate in the food-restricted and food-restricted + exercise-trained groups were significantly lower than that of control rats. In the treatment study, ion-activity products of calcium oxalate index in food-restricted + exercise-trained rats was significantly lower than that of control rats. Conclusions Weight loss intervention seems to reduce the risk of uric acid stone formation by improving low urine pH and calcium oxalate stone formation by increasing urinary citrate excretion. The present study provides the first theoretical evidence to support weight loss intervention programs for nephrolithiasis patients with metabolic syndrome.

Objective To validate two prediction models (European Organization for Research and Treatment of Cancer and Spanish Urological Club for Oncological Treatment) for recurrence and progression of non-muscle invasive bladder cancer in Japanese patients who underwent bacillus Calmette–Guerin instillation therapy. Methods From March 1985 to April 2007, data were analyzed from 366 patients who underwent transurethral resection of bladder tumor followed by bacillus Calmette–Guerin instillation therapy. The ability of two scoring models to predict recurrence and progression was assessed by concordance index. Results For recurrence probability, the concordance index of the European Organization for Research and Treatment of Cancer and Spanish Urological Club for Oncological Treatment models was 0.514 and 0.576, respectively, which was lower than that (0.604) of a selected single prognostic factor (age) by our multivariate analysis. For progression probability, the concordance index of European Organization for Research and Treatment of Cancer and Spanish Urological Club for Oncological Treatment models was 0.693 and 0.764, respectively, which was higher than that (0.633) of a selected single factor (T stage) by our multivariate analysis. The Spanish Urological Club for Oncological Treatment scoring system resulted in better stratification of tumor recurrence and progression when compared with the European Organization for Research and Treatment of Cancer model, probably because more patients underwent bacillus Calmette–Guerin treatment in the Spanish Urological Club for Oncological Treatment cohort than in the European Organization for Research and Treatment of Cancer cohort. Conclusions The Spanish Urological Club for Oncological Treatment scoring system is a good predictor of tumor recurrence and progression in Japanese patients who underwent bacillus Calmette–Guerin immunotherapy. A large prospective study is warranted to confirm the efficacy of this system.

What’s known on the subject? and What does the study add? The expression of hENT1 was significantly associated with prolonged survival in advanced bladder cancer treated with gemcitabine–cisplatin-based combination chemotherapy. The mechanism-based approach to the chemotherapeutic agents may be helpful to personalize medicine for the individual advanced bladder cancer patient. OBJECTIVE To evaluate the expression of the human equilibrative nucleoside transporter 1 (hENT1) and excision repair cross complementing 1 (ERCC1) as possible prognostic factors for patients with metastatic bladder cancer treated with gemcitabine–cisplatin-based combination chemotherapy. PATIENTS AND METHODS The present study retrospectively evaluated the expression of hENT1 and ERCC1 by immunostaining in chemo-naive primary bladder tumour specimens from 40 patients with metastatic bladder cancer who received treatment with gemcitabine–cisplatin-based combination chemotherapy at Wakayama Medical University Hospital and affiliated hospitals from May 2002 to July 2009. Immunohistochemistry on formalin-fixed, paraffin-embedded tissues was performed with specific hENT1 and ERCC1 antibodies scored by two pathologists who were blinded to clinical outcomes. The clinical and histopathological variables were analyzed to evaluate predictive values for survival. RESULTS The median survival time in patients with high and low hENT1 expression was 17.3 and 11.6 months, respectively (log-rank test, P= 0.003). This contrasted with the median survival in patients with high and low ERCC1 expressions, which did not differ significantly (high ERCC1, 13.6 months; low ERCC1, 17.1 months; P= 0.178). In univariate Cox regression analyses for pretreatment clinicopathological variables, performance status (P= 0.02) and hENT1 expression (P= 0.004), but not ERCC1 expression (P= 0.182), were associated with overall survival. Multivariate analysis using a Cox proportional hazards model showed that hENT1 expression was an independent prognostic factor (P= 0.008). CONCLUSION The data obtained in the present study show that high expression of hENT1 in tumour cells is associated with prolonged survival in patients with metastatic bladder cancer treated with gemcitabine–cisplatin-based combination chemotherapy.

OBJECTIVE To investigate the association between metabolic syndrome and urinary stone disease, and whether insulin resistance associated with adiposity affects the risk of urinary stone formation, using a rat model of metabolic syndrome. MATERIALS AND METHODS Four-week-old male Otsuka Long-Evans Tokushima 'Fatty' (OLETF, a model of human type 2 diabetes and metabolic syndrome) rats, and Long-Evans Tokushima (LETO, a non-diabetic control) rats (10 each) were given a standardized diet and free access to water. Body weight and serum and urinary biochemistry were determined every 4 weeks. Ten-week-old male OLETF and LETO rats were divided into three groups of nine each and treated with vehicle or oral administration of 3 or 10 mg/kg/day pioglitazone, an agent that improves insulin resistance. After 4 weeks, body weight and serum and urinary biochemistry were determined. RESULTS The OLETF rats had significantly lower urinary pH and citrate excretion, and higher urinary uric acid and calcium excretion, than the LETO rats, with increases in body weight, serum triglyceride, glucose and insulin. The administration of pioglitazone to the OLETF rats for 4 weeks significantly increased urinary pH dose-dependently. There was no change in the urinary excretion of citrate, uric acid, calcium, oxalate or magnesium. CONCLUSION These results indicate that metabolic syndrome causes the changes in urinary constituents, leading to increased risk of both uric acid and calcium stone formation. Improvement in insulin resistance, a central cause of metabolic syndrome, might prevent uric acid stone formation by raising urinary pH.