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Purpose Current guidelines do not yet provide any recommendations for adjuvant chemotherapy in patients with upper tract urothelial carcinoma managed with radical nephroureterectomy. We evaluated whether an adjuvant chemotherapeutic regimen would affect the clinical outcome in patients with high risk upper tract urothelial carcinoma. Materials and Methods We identified 873 patients who had undergone radical nephrouretectomy for localized upper tract urothelial carcinoma at 14 Japanese institutions between 1993 and 2011. We assessed whether the type of regimen, such as methotrexate, vinblastine, doxorubicin and cisplatin, and gemcitabine and cisplatin, in an adjuvant setting, could affect the subsequent clinical outcome of patients with upper tract urothelial carcinoma. Results On multivariate analysis pathological T stage, tumor grade, lymphovascular invasion and lymph node involvement were prognostic factors for recurrence-free survival and cancer specific survival. We defined 229 patients with 3 or more of these factors as the high risk group. In an analysis according to adjuvant regimen, Kaplan-Meier curves showed that the 1 and 2-year recurrence-free survival rates in the methotrexate, vinblastine, doxorubicin and cisplatin treated group were 71.4% and 47.9%, which were significantly higher than in the gemcitabine and cisplatin treated group (48.2% and not reached, p=0.022) or those not treated with adjuvant chemotherapy (53.4% and 39.6%, p=0.039). Similar results were observed in terms of cancer specific survival. Conclusions Our study showed that pT3-4, tumor grade 3, positive lymphovascular invasion and lymph node involvement were independent risk factors for disease mortality in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy. In the high risk group methotrexate, vinblastine, doxorubicin and cisplatin adjuvant chemotherapy contributed to improve subsequent mortality compared to gemcitabine and cisplatin or no adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Purpose: Recently several prognostic nomograms have been developed to predict the prognosis of malignant diseases, including renal cell carcinoma. However, to our knowledge a preoperative prognostic nomogram that predicts survival in patients with renal cell carcinoma is not available. We developed a preoperative nomogram based on the TNM classification that predicts cause specific survival in patients with renal cell carcinoma. Materials and Methods: A total of 545 patients with renal cell carcinoma, including metastatic disease, who underwent radical nephrectomy or nephron sparing surgery at our institution were included in the study. Cases were staged according to the 2002 UICC TNM system, 6th edition. T, N and M factors were used as prognostic factors and a Cox proportional hazards regression model was developed to predict cause specific survival. A nomogram to predict cause specific survival was developed by repeating the analysis on 200 bootstrap samples. To validate the nomogram a concordance index was estimated and calibration was also examined by plotting the predictions made by the nomogram. Results: Overall 1, 3 and 5-year patient survival was 95.2%, 92.0% and 89.9%, respectively. T, N and M factors were significant prognostic factors in the Cox proportional hazards regression model. Using the combined TNM factors we developed a nomogram predicting 1, 3 and 5-year cause specific survival rates. The nomogram had excellent ability to discriminate, as evidenced by a concordance index of 0.81, and it was generally well calibrated. Conclusions: The preoperative information shown by this nomogram may be important for obtaining informed consent from patients with renal cell carcinoma who have indications for surgery. [Copyright &y& Elsevier]

Purpose: Recent studies suggest that alterations in chromatin structure by histone acetylation may have an important role in the neoplastic process. We evaluated histone H3 acetylation in renal cell carcinoma and the effects of a histone deacetylase inhibitor on renal cancer cell lines. Materials and Methods: The expression of acetylated histone H3 (Lys9) in renal cell carcinoma and corresponding nonneoplastic tissue specimens was evaluated. We next assessed immunohistologically the relationships between acetylated histone H3 expression and clinicopathological parameters in 44 cases of renal cell carcinoma. Furthermore, we evaluated the effects of the histone deacetylase inhibitor depsipeptide on the renal cancer cell lines Caki-1, ACHN, 769P and 786O (ATCC®). Results: Acetylated histone H3 expression was decreased in 85.0% of renal cell carcinomas compared to levels in nonneoplastic tissue. Decreased expression was related to high nuclear tumor grade and advanced pathological tumor stage (p = 0.048 and 0.032, respectively). Depsipeptide inhibited cell line proliferation in a time and dose dependent manner. Depsipeptide induced apoptosis in Caki-1, ACHN and 786O, and induced G2 cell cycle arrest in 769P. Concomitantly depsipeptide increased acetylated histone H3 and p21WAF/CIP1 expression, and induced Bcl-2 phosphorylation. Conclusions: These results suggest that the decreased acetylation of histone H3 is a common alteration in a malignant phenotype of renal cell carcinoma. Increasing the amount of acetylated histone H3 might be a therapeutic option for renal cell carcinoma. [Copyright &y& Elsevier]

Purpose: Extracorporeal shock wave lithotripsy is currently accepted as a first line treatment modality for urolithiasis. In obtaining informed consent it is important to inform patients of the stone-free rate with extracorporeal shock wave lithotripsy before surgery. The present study was performed to develop preoperative nomograms for predicting stone-free rates after extracorporeal shock wave lithotripsy. Materials and Methods: A total of 435 patients with 507 urinary stones were treated with extracorporeal shock wave lithotripsy with a Dornier Lithotripter D. Patient age, sex, body mass index, number of stone(s) in each treatment, stone length, side and location were evaluated before extracorporeal shock wave lithotripsy, and treatment efficacies were evaluated at 3 months after each session. The treated stones were divided into 2 groups, those in cases that were stone-free with a single extracorporeal shock wave lithotripsy session and those in all other cases. Multivariate analysis was performed using a logistic regression model. The nomograms were developed by repeating the analysis on 200 bootstrap samples. Results: Stone length, location and number were identified as significant variables on multivariate analysis, and a logistic regression model was developed using these variables. The nomograms predicting stone-free rate at 3 months after single extracorporeal shock wave lithotripsy treatment were finally developed from 200 bootstrap samples. In these nomograms the stone-free probability was highest for solitary proximal ureteral stones less than 5 mm in size (93.8%) and lowest for multiple caliceal stones greater than 21 mm (10.5%). Conclusions: This study demonstrated that stone size, location and number are significant predictors of extracorporeal shock wave lithotripsy outcome. We have developed nomograms for predicting the stone-free rate of extracorporeal shock wave lithotripsy, which is useful for counseling patients with urolithiasis before surgery. [Copyright &y& Elsevier]