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Purpose: Few studies have evaluated changes in erectile function with time before and after prostate brachytherapy using the International Index of Erectile Function-15, a sensitive, validated tool for assessing male sexual dysfunction. In this prospective study we evaluated the natural history of erectile function after prostate brachytherapy without supplemental therapy (external beam radiotherapy, phosphodiesterase-5 inhibitors or androgen deprivation therapy) using the International Index of Erectile Function-15., Materials and Methods: We identified 119 patients who were followed at least 12 months after prostate brachytherapy between 2004 and 2010. Sexual and erectile function status were assessed before brachytherapy (baseline), and 3, 6, 12, 18, 24 and 36 months postoperatively using the International Index of Erectile Function-15., Results: Mean total International Index of Erectile Function-15 score, and scores on the erectile function, orgasmic function, sexual desire and intercourse satisfaction domains 3 months after brachytherapy were significantly lower than at baseline (p <0.05). They remained lower until 36 months after prostate brachytherapy. Erectile function was maintained 12 months after brachytherapy in 16 of the 48 men (33.3%) with a baseline erectile function domain score of 11 or greater. There was no significant difference in clinical features except the age of patients who maintained the erectile function domain score and their counterparts 12 months after brachytherapy. Multivariate analysis revealed that age 70 years or greater was the only predictive factor for deteriorating erectile function after brachytherapy (p = 0.035)., Conclusions: Findings indicate a global decrease in all domains of the International Index of Erectile Function-15 score 12 months after prostate brachytherapy. Also, patient age may influence the preservation of brachytherapy related potency., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: An increase in the pretreatment neutrophil-to-lymphocyte ratio is associated with poor prognosis for various cancers, including renal cell carcinoma. However, the clinical implication of a posttreatment change in the neutrophil-to-lymphocyte ratio in patients with cancer remains unclear., Materials and Methods: We reviewed the records of 250 patients with nonmetastatic clear cell renal cell carcinoma and analyzed associations among clinicopathological variables, the preoperative and postoperative neutrophil-to-lymphocyte ratio, and recurrence-free survival., Results: The 10-year recurrence-free survival rate for patients with a preoperative neutrophil-to-lymphocyte ratio of 2.7 or greater was significantly lower than that for those with a ratio of less than 2.7 (64.4% vs 83.7%, p = 0.0004). When combined with the postoperative ratio, patients with a preoperative ratio of 2.7 or greater could be further divided into 2 groups with a significantly different prognosis. The 10-year recurrence-free survival rate for patients with a preoperative neutrophil-to-lymphocyte ratio of 2.7 or greater and postoperative ratio of less than 2.7 was significantly lower than that for those with a preoperative and postoperative ratio of 2.7 or greater (52.0% vs 83.5%, p = 0.0487). The latter was similar to the 83.7% for patients with a preoperative ratio of less than 2.7. In patients with recurrence the ratio at recurrence was significantly increased compared with the postoperative ratio (mean ± SD 2.82 ± 1.63 vs 2.00 ± 0.90, p = 0.0090). Multivariate analysis showed that tumor size, pathological tumor stage and the neutrophil-to-lymphocyte ratio change (a combination of the preoperative and postoperative ratios) were independent predictors of recurrence. Using these 3 significant variables patients were stratified into low, intermediate and high risk groups, among which the recurrence-free survival rate significantly differed., Conclusions: The posttreatment neutrophil-to-lymphocyte ratio change was a significant prognostic factor for recurrence as well as tumor size and pathological tumor stage in patients with clear cell renal cell carcinoma., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: From the perspective of oncological and functional outcomes partial nephrectomy is considered standard surgery for small renal tumors 4 cm or less. However, radical nephrectomy is commonly done for small tumors. It is important to predict postoperative renal function in patients to choose the most optimal surgical procedure., Materials and Methods: We retrospectively reviewed the records of 271 patients treated with radical nephrectomy for renal cell carcinoma. Associations of tumor size and clinical variables with renal function were analyzed., Results: Preoperatively the mean ± SD glomerular filtration rate was 74.38 ± 17.70 ml per minute/1.73 m(2) and 56 patients (20%) had renal insufficiency (glomerular filtration rate less than 60 ml per minute/1.73 m(2)). The mean decrease in the glomerular filtration rate after radical nephrectomy was 24.2 ± 12.40 ml per minute/1.73 m(2) (31.5% ± 15%). Of 215 patients with a preoperative glomerular filtration rate of 60 ml per minute/1.73 m(2) or greater 165 (77%) had new onset renal insufficiency. Age, tumor size, preoperative glomerular filtration rate and hypertension were significantly associated with new onset renal insufficiency. Multivariate analysis revealed that age 60 years or greater, tumor size 7 cm or less and the preoperative glomerular filtration rate were independent risk factors for new onset renal insufficiency (p <0.05). Finally, we developed a predictive model for new onset renal insufficiency after radical nephrectomy., Conclusions: Tumor size 7 cm or less, age 60 years or greater and a decreased preoperative glomerular filtration rate were significant risk factors for new onset renal insufficiency in patients treated with radical nephrectomy. Partial nephrectomy might be considered an option according to the risk of postoperative renal insufficiency, especially in elderly patients with a tumor of 7 cm or less., (Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We investigated the prognostic significance of the neutrophil-to-lymphocyte ratio to predict recurrence in patients with nonmetastatic renal cell carcinoma., Materials and Methods: We retrospectively reviewed the records of 192 patients with nonmetastatic renal cell carcinoma (T1-4N0M0) who underwent nephrectomy between 1986 and 2000. Mean followup was 93 months (range 6 to 232) months. We assessed the prognostic value of the pretreatment neutrophil-to-lymphocyte ratio, and other clinical and laboratory parameters on univariate and multivariate analysis., Results: Presentation mode, tumor stage, C-reactive protein, lymphocyte count and the neutrophil-to-lymphocyte ratio significantly correlated with recurrence-free survival on univariate analysis. The recurrence-free survival rate in patients with a neutrophil-to-lymphocyte ratio of less than 2.7 was 93.7% at 5 years and 79.8% at 10 years, significantly higher than the 77.9% and 58.4%, respectively, in patients with a ratio of 2.7 or greater (p = 0.0205). Multivariate analysis revealed that T stage and the neutrophil-to-lymphocyte ratio were independent predictors of recurrence. The 10-year survival rate in patients at low risk (T2 or less and neutrophil-to-lymphocyte ratio less than 2.7), intermediate risk (T2 or less and ratio 2.7 or greater, or T3 or greater and ratio less than 2.7) and high risk (T3 or greater and ratio 2.7 or greater) was 82.0%, 63.6% and 33.0%, respectively, which were significantly different., Conclusions: An increased pretreatment neutrophil-to-lymphocyte ratio is an independent predictor of recurrence. The combination of T stage and the neutrophil-to-lymphocyte ratio can be used to stratify recurrence risk in patients with nonmetastatic renal cell carcinoma., (2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

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.

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.

Purpose: We investigated the prognostic impact of lymphovascular invasion (LVI) and traditional prognostic factors for survival in a large series of patients treated surgically for upper tract transitional cell carcinoma (TCC). We also developed a prognostic factors-based model for risk stratification of upper tract TCC., Materials and Methods: We identified a study population of 173 consecutive patients treated surgically for upper tract TCC at our institution between 1980 and 2002. We compared LVI with other pathological features and determined the disease specific survival rate., Results: LVI was found in 52 patients (30.1%). As tumor grade and pathological stage increased, the incidence of LVI increased significantly. LVI was found in 12 of 133 patients (9.0%) without lymph node metastasis compared with 40 of 40 patients (100%) with lymph node metastasis. Five and 10-year disease specific survival rates were 84.9% and 80.4% in the absence of LVI, and 40.2% and 21.1% in the presence of LVI, respectively (p <0.001). In multivariate analysis LVI, pathological T stage and tumor grade were independent predictors for disease specific survival. The relative risk of death could be expressed with the formula, exp(0.729 x tumor grade + 1.659 x pathological T stage + 1.160 x LVI). Using this equation the patients were stratified into low risk (grade 1 or 2, LVI negative, stage pT2 or lower), high risk (any tumor grade, LVI positive, stage pT3 or greater) and intermediate risk (all others) groups with significant differences in survival. Five and 10-year disease specific survival rates were 93.0% and 89.4% in the low risk group (82 patients), 66.8% and 62.9% in the intermediate risk group (53 patients), and 25.6% and 0% in the high risk group (38 patients), respectively., Conclusions: In addition to pathological stage and tumor grade, LVI is an independent prognostic factor for disease specific survival in upper tract TCC. Patients in the high and/or intermediate risk groups may benefit from integrated therapies with surgery and postoperative systemic chemotherapy.

Purpose: The indications for repeat prostate biopsy for persistently increased prostate specific antigen (PSA) in men with prostate cancer never detected on previous biopsy are not clear. In this study we determined that PSA adjusted for transition zone (TZ) epithelial volume is the most powerful predictor for detecting prostate cancer on repeat biopsy., Materials and Methods: Repeat prostate biopsies including additional TZ cores were performed in 75 men with PSA between 4.0 and 10.0 ng/ml. TZ epithelial volume was calculated by multiplying TZ volume by the percent of epithelium, which was measured by morphometric analysis using image analysis computer software., Results: Prostate cancer was detected on repeat biopsy in 19 of the 75 patients. Patients with prostate cancer had a significant smaller percent area of epithelium or glandular lumen than those without cancer. In patients without prostate cancer TZ epithelial volume significantly correlated with total PSA. According to ROC analysis PSA adjusted for TZ epithelial volume had the greatest AUC for cancer detection (0.879). This parameter was able to avoid more than 90% of unnecessary repeat biopsies with 90% sensitivity. Multiple logistic regression analysis showed that PSA complex adjusted for TZ epithelial volume was the significant independent predictor of cancer., Conclusions: PSA adjusted for TZ epithelial volume is the most powerful predictor of cancer in men who have undergone previous negative prostate biopsies and in whom PSA remains between 4.0 and 10.0 ng/ml.

Purpose: Since middle-aged and elderly patients seem to have risk factors affecting renal function, it is important to predict postoperative renal function prior to unilateral nephrectomy (UNx). We evaluated preoperative factors for predicting postoperative renal function in middle-aged and elderly patients with renal cell carcinoma (RCC) treated with radical nephrectomy (RNx)., Materials and Methods: In 201 patients who underwent RNx preoperative records and postoperative serum creatinine (SCR) 6 years after nephrectomy were available. Postoperative renal insufficiency was defined as serum creatinine 1.4 mg/dl or greater. The relationship of each preoperative and postoperative factor was analyzed. Logistic regression analysis was performed to evaluate preoperative factors for predicting postoperative SCR 1.4 mg/dl or greater after 6 years., Results: There was a significant difference in postoperative SCR between female and male patients, and between those with and without hypertension, diabetes and proteinuria (p <0.05). Age, hemoglobin, preoperative SCR, blood urea nitrogen, uric acid and K significantly correlated with postoperative SCR (p <0.05). The increase in SCR during 6 years after UNx was significantly higher in patients with hypertension, diabetes and proteinuria than in their respective counterparts (p <0.05). Multivariate stepwise logistic regression analysis demonstrated that preoperative serum creatinine, hypertension and proteinuria were significant independent factors predicting postoperative renal function 6 years after UNx in patients with RCC (p <0.05)., Conclusions: Preoperative SCR, hypertension and proteinuria are useful factors for predicting postoperative renal function after RNx in patients with RCC.

Purpose: Bcl-2 has been shown to prolong cancer cell survival by blocking apoptosis and have the function of scavenging reactive oxygen species. We assessed the efficacy of a novel strategy that relies on antisense bcl-2 oligodeoxynucleotides as well as a glutathione depletor combined with diethylstilbestrol (DES) for hormone independent prostate cancer., Materials and Methods: The cytotoxic effects of antisense bcl-2 oligodeoxynucleotides and DES on PC-3 cells were determined using spectrophotometry measurement. The expression of Bcl-2 protein was detected by Western blot analysis. Intracellular reactive oxygen species generation was estimated from the amount of intracellular dichlorofluorescein. Apoptosis was determined by the terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate-biotin nick end labeling assay., Results: Antisense bcl-2 oligodeoxynucleotides decreased Bcl-2 protein levels and significantly inhibited PC-3 cell growth in a dose dependent manner. Antisense bcl-2 oligodeoxynucleotides significantly enhanced DES induced cytotoxicity. A significant increase in apoptotic cells was induced by the combination of antisense bcl-2 oligodeoxynucleotides and DES compared with the oligodeoxynucleotides alone. The glutathione depletor buthionine sulfoximine significantly decreased the intracellular concentration of glutathione and augmented DES induced cytotoxicity and reactive oxygen species generation in PC-3 cells. Neither the generation of reactive oxygen species nor the intracellular concentration of glutathione was influenced by antisense bcl-2 oligodeoxynucleotide treatment., Conclusions: Antisense bcl-2 oligodeoxynucleotides significantly enhanced DES induced cytotoxicity in hormone independent prostate cancer cells through the apoptotic pathway independent of augmented reactive oxygen species generation, whereas the glutathione depletor augmented cytotoxicity and reactive oxygen species generation.

Purpose: To our knowledge the indications for repeat prostate needle biopsy in men whose previous transrectal ultrasound guided biopsy results revealed no evidence of cancer have not yet been defined. We identified the most effective method for detecting prostate cancer on repeat biopsy., Materials and Methods: One or more systematic repeat prostate biopsies were performed in 144 consecutive patients, including 86 with prostate specific antigen (PSA) levels between 4 and 10 ng./ml. at repeat biopsy. Men in whom cancer was detected on repeat biopsies were compared with their counterparts in terms of digital rectal examination findings, PSA based parameters and an atypical prostate on initial prostate biopsy., Results: Prostate cancer was detected on repeat biopsy in 39 of the 144 patients and in 19 on subset analysis of 86. Serum PSA levels at repeat biopsy did not differ significantly in patients with and without prostate cancer. According to receiver operating characteristics analysis the alpha1-antichymotrypsin-PSA complex adjusted for transition zone volume had the greatest area under the curve values, that is 0.756 for all 144 patients and 0.768 for the subset analysis of 86. Multiple logistic regression analysis of the subset of 86 patients showed that alpha1-antichymotrypsin-PSA complex adjusted for transition zone volume was the only significant independent predictor of cancer., Conclusions: alpha1-Antichymotrypsin-PSA complex adjusted for transition zone volume was the most powerful predictor of cancer in men who had undergone previous negative prostate biopsies. This parameter may be used to avoid more unnecessary repeat biopsies with an acceptable decrease in sensitivity.

Purpose: Although tumor necrosis factor-alpha (TNF-alpha) induces a strong cytotoxic effect on cell growth, many authors have reported that various cancer cells are resistant to TNF-alpha and the basis for this sensitivity or resistance to TNF-alpha remains to be elucidated. Since nuclear factor kappa B (NF-kappaB) activation has recently been reported to inhibit TNF-alpha-induced cell death, we studied whether NF-kappaB also assumes a protective role in TNF-alpha-induced cell death in prostate cancer cells., Materials and Methods: We used two human prostate cancer cell lines of DU145 and PC-3. We prepared two different NF-kappaB inhibitors, pyrrolidine dithiocarbamate (PDTC) and NF-kappaB decoy. NF-kappaB DNA binding activity was detected by electrophoretic mobility shift assay (EMSA). Cell survivals were measured by MTT assay. Induction of apoptosis was detected by nuclear staining and measured by fragmented DNA ELISA., Results: EMSA showed that NF-kappaB inhibitors continuously inhibited TNF-alpha-induced NF-kappaB activation. Cell growth was not inhibited by either TNF-alpha (50 ng./ml. or less) or NF-kappaB inhibitors. However, both PCA cells treated with TNF-alpha (20 ng./ml.) plus NF-kappaB inhibitors showed significant growth inhibition compared with controls (p<0.05). Nuclei of PCA cells appeared severely fragmented by this combination therapy. Furthermore, the levels of DNA fragmentation were significantly elevated in PCA cells treated with TNF-alpha (20 ng./ml.) plus NF-kappaB inhibitors compared with controls (p<0.05)., Conclusions: NF-kappaB activation is suggested to produce the resistance of DU145 and PC-3 to TNF-alpha and that the combination of TNF-alpha and NF-kappaB inhibitors could be constituted an effective therapy to TNF-alpha-resistant human prostate cancer cells.

Purpose: We reviewed 17 resected pheochromocytomas comprising 7 from symptomatic patients, and 10 unsuspected and incidentally discovered tumors. We compared various parameters concerning these 2 groups and investigated the features of the incidentally discovered pheochromocytoma., Materials and Methods: Patient gender and age, clinical symptoms and signs, tumor localization, detection methods, findings on imaging studies, urinary catecholamine concentrations, results of metoclopramide stimulation tests, treatments at operation and tumor size were evaluated. Furthermore, we compared the clinically diverse aspects arising between the symptomatic and incidentally discovered pheochromocytomas., Results: The 24-hour urinary noradrenaline and vanillylmandelic acid levels in the incidental cases tended to be lower than those in the symptomatic cases, while 24-hour urinary dopamine was significantly less (468 +/- 221 compared to 1,558 +/- 899 microg./day, respectively). Typical symptoms of pheochromocytoma were noted in 6 patients (60%) in the incidental tumor group. The incidental cases had a markedly high false-negative rate (71%) as noted by the metoclopramide stimulation test, although the symptomatic cases had a 100% positive rate. On the other hand, the average diameter of incidental tumors was significantly larger than that of the symptomatic lesions (55.5 +/- 19.1 versus 35.9 +/- 12.1 mm., respectively)., Conclusions: Clinical signs and findings in patients with incidental tumors were weaker than those with symptomatic disease although most incidental tumors functioned. Lower urinary catecholamine values in the incidental tumors were consistent with these results. However, the surgical risk for incidental tumors was the same as that for symptomatic lesions. Therefore, patients with incidentally discovered pheochromocytomas scheduled to undergo surgery should be treated accordingly.

Purpose: Carboxyterminal propeptide of type 1 procollagen (P1CP) is believed to be a marker of new bone formation. We investigated the possible application of serum P1CP as a biochemical marker for bone metastases in patients with prostate cancer., Materials and Methods: Prostate specific antigen (PSA), prostatic acid phosphatase (PAP), P1CP and alkaline phosphatase were measured in 136 serum samples from 79 patients with untreated prostate cancer, 29 with stage D2 disease in remission and 28 with progressive stage D2 carcinoma., Results: Serum P1CP and alkaline phosphatase were significantly elevated in untreated patients with a positive bone scan (278.9 +/- 61.9 ng./ml. and 826.5 +/- 176.3 international units per 1., respectively) compared to those with a negative bone scan (104.2 +/- 4.2 and 200.8 +/- 9.1, respectively, p <0.05). The areas under receiver operating characteristics curves were 0.86 for P1CP, 0.87 for alkaline phosphatase, 0.88 for PSA and 0.85 for PAP. The best accuracy rates for P1CP, alkaline phosphatase, PSA and PAP to predict bone lesions were 84, 87, 86 and 84%, respectively. P1CP provided a greater specificity and positive predictive value. These serum markers correlated significantly with the extent of disease on bone scan (p <0.05). The incidence of positive serum P1CP and alkaline phosphatase decreased significantly in response to endocrine therapy in patients with bone metastasis, and increased progressively in association with progression of the tumor (p <0.05) parallel to PSA and PAP., Conclusions: These findings suggest that serum P1CP is a useful indicator for predicting bone metastases.

We previously reported that flow cytometric bromodeoxyuridine/deoxyribonucleic acid (DNA) bivariate analysis can provide important information on the malignant potential of bladder cancer. Therefore, in the current study we further evaluated upper tract urothelial tumors to clarify whether DNA/bromodeoxyuridine bivariate analysis can provide additional prognostic information on patients with upper tract urothelial tumor. A total of 43 upper tract urothelial tumors that were resected by nephroureterectomy was analyzed. Flow cytometric DNA ploidy and bromodeoxyuridine labeling were determined by an in vitro bromodeoxyuridine labeling method. DNA diploid tumors were associated with an 85.9% 3-year survival rate compared to 36.5% for DNA aneuploid tumors. On the other hand, 11 high bromodeoxyuridine labeled tumors demonstrated a 16.4% 3-year survival rate compared to 82.4% for those with low bromodeoxyuridine labeled tumors. Multivariate survival analysis using the Cox proportional regression model was performed to identify the most informative factors for prognosis, with the single most important factor being histological tumor stage. Nearly as important and the next factor to be chosen was tumor grade, followed by bromodeoxyuridine labeling index status. DNA ploidy status did not influence clinical outcome. Thereafter, when actuarial 3-year survival rates according to the bromodeoxyuridine labeling index status in grade 3 tumors were estimated, 68.4% and 16.7% 3-year survival rates were observed in cases of low and high bromodeoxyuridine labeling index tumors, respectively. These results indicate that flow cytometric bromodeoxyuridine/DNA bivariate analysis may be useful in dividing patients with grade 3 upper tract urothelial carcinoma into 2 different prognosis groups.