Suberoylanilide Hydroxamic Acid Can Re-sensitize a Cisplatin-Resistant Human Bladder Cancer.

Cisplatin chemotherapy is the standard treatment for metastatic urothelial carcinoma. Although there are second-line chemotherapeutic agents approved by the U.S. Food and Drug Administration (FDA) such as those targeting programmed death-ligand 1 (PD-L1), more effective pharmacotherapy is required for cisplatin-resistant bladder cancer due to its limited overall survival and progression-free survival. The synergistic anti-cancer effect of cisplatin and suberoylanilide hydroxamic acid (SAHA) in cisplatin-resistant bladder cancer cells (T24R2) was examined. Tumor cell proliferation and cell cycle was examined using the cell counting kit (CCK)-8 assays and flow cytometry, respectively. Synergism was examined using the combination index (CI). CCK-8 assay and CI test were used to observe the strong synergistic anti-cancer effect between SAHA and cisplatin. Activation of caspase mediated apoptosis, down-regulated expression of the anti-apoptotic B-cell lymphoma-2 (Bcl-2) and up-regulated expression of pro-apoptotic Bcl-2-associated death promoter (BAD) were observed in Western blot. SAHA synergistically could partially re-sensitize cisplatin-resistant bladder cancer cells (T24R2) through the cell cycle arrest and induction of apoptosis pathway. SAHA-based treatment could be a potential treatment regimen in patients with cisplatin resistant bladder cancer.

Antitumor effects of MutT homolog 1 inhibitors in human bladder cancer cells.

As standard second-line regimen has not been established for patients who are refractory to or relapse with cisplatin-based chemotherapy, an effective class of novel chemotherapeutic agents is needed for cisplatin-resistant bladder cancer. Recent publications reported that MutT homolog 1 (MTH1) inhibitors suppress tumor growth and induce impressive therapeutic responses in a variety of human cancer cells. Few studies investigated the cytotoxic effects of MTH1 inhibitors in human bladder cancer. Accordingly, we investigated the antitumor effects and the possible molecular mechanisms of MTH1 inhibitors in cisplatin-sensitive (T24) and - resistant (T24R2) human bladder cancer cell lines. These results suggest that TH588 or TH287 may induce cancer cell suppression by off-target effects such as alterations in the expression of apoptosis- and cell cycle-related proteins rather than MTH1 inhibition in cisplatin-sensitive and - resistant bladder cancer cells.Abbreviations: MTH: MutT homolog; ROS: reactive oxygen species; CCK-8: cell counting kit-8; DCFH-DA: dichlorofluorescein diacetate; PARP: poly (ADP-ribose) polymerase.

Incidence and risk factors of 30-day early and 90-day late morbidity and mortality of radical cystectomy during a 13-year follow-up: a comparative propensity-score matched analysis of complications between neobladder and ileal conduit.

OBJECTIVE: We report on the short and late morbidity and mortality of ileal conduit and neobladder after radical cystectomy with their associated risk factors. METHODS: We retrospectively collected data on 308 non-metastatic bladder cancer patients who underwent radical cystectomy with either ileal conduit or neobladder for a curative intent from January 1999 to December 2011. Post-operative morbidity and mortality of 30-day (early) and 90-day (late) complication with their risk factors were examined in association with different types of urinary diversion. A comparative analysis using propensity-score matching was performed with matching variables of age, sex, number of underlying diseases and pathologic T and N stages, lymph node dissection, operative time and time of surgical year for comparison of the early and late morbidities between ileal conduit and neobladder. RESULTS: During the median follow-up of 46.6 months, early and late morbidities were 29.5% (n=91) and 19.8% (n=61), and complication-related mortalities were 2.2 and 6.6%, respectively. The type of urinary diversion significantly affected only the late complications (early: neobladder 57 vs. ileal conduit 47, P=0.096; late: neobladder 67 vs. ileal conduit 37, P<0.001). However, after propensity-score matching, no significant differences in early and late morbidities were observed between neobladder and ileal conduit. For risk factors of morbidity, number of removed lymph node states and hypertension were independently significant for both early and late complications (P<0.05). CONCLUSIONS: The type of urinary diversion affected only late complication, however, results of the matching analysis showed no significant differences in early and late morbidities between neobladder and ileal conduit.

Localized non-conventional renal cell carcinoma: prediction of clinical outcome according to histology.

OBJECTIVE: A wide variety of parameters have been investigated in the prognostic significance of non-conventional clear cell renal cell carcinoma. Aim of the present study was to compare its clinical outcome and to determine the independent prognostic factors according to the histology. METHODS: This retrospective study enrolled localized non-conventional clear cell renal cell carcinomas (T1a-T4N0M0), including Xp11.2 translocation (Xp11.2t), all surgically treated in a single institution between 1988 and 2011. The study statistically analyzed the clinicopathological parameters to compare the prognostic outcomes among the different histological subtypes of non-conventional clear cell renal cell carcinoma and to define any independent prognostic factors. RESULTS: A total of 374 cases were examined, including 126 papillary (33.7%), 164 chromophobe (43.9%), eight collecting duct (2.1%), 40 unclassified (10.7%), 16 Xp11.2t (4.3%), seven mucinous tubular and spindle cell (1.8%) renal cell carcinomas and 13 oncocytomas (3.5%). The mean follow up was 56.4 months, with s mean tumor size of 4.9 ± 3.4 cm. The 4-year recurrence-free survival, overall survival and cancer-specific survival were inversely related to the increase of pathological T stages (P < 0.001). For histological type other than 13 oncocytomas and seven mucinous tubular and spindle cell renal cell carcinomas, the chromophobe showed the best prognosis of survival, followed by papillary, Xp11.2t, unclassified and collecting duct renal cell carcinomas, in this order. All survival rates were significantly different, as according to the histology (P = 0.009). The significant prognostic factors were preoperative body mass index (hazard ratio 0.76), serum albumin (hazard ratio 0.64), T stage (hazard ratio 2.28), the sarcomatoid differentiation (hazard ratio 33.45) and lymphovascular invasion (hazard ratio 12.40) in pathology (P < 0.05). CONCLUSIONS: Different non-conventional clear cell renal cell carcinoma subtypes have significantly different clinical characteristics of prognosis with many suggestive predictive factors of survival.

The role of c-FLIP in cisplatin resistance of human bladder cancer cells.

PURPOSE: We investigated the mechanisms underlying cisplatin resistance in human bladder cancer cells to provide novel molecular targets for the treatment of cisplatin resistant bladder cancer. MATERIALS AND METHODS: The differential gene expression of cisplatin sensitive (T24) and resistant (T24R2) human bladder cancer cell lines was analyzed and validated by microarray and Western blot analysis. Changes in cisplatin sensitivity by c-FLIP knockdown and related mechanisms in T24R2 cells were assessed using the Cell Counting Kit-8 assay (Dojindo Molecular Technologies, Gaithersburg, Maryland) and Western blot. siRNA oligonucleotides that specifically target c-FLIP were prepared and siRNA transfection was done. RESULTS: Microarray analysis revealed that the expression of 1,086 and 322 genes showed more than twofold and fourfold changes in the T24R2 and T24 cell lines, respectively. Especially genes involved in the c-FLIP related death receptor apoptosis pathway, including caspase 2 and 9, NF-kB, BID, c-FLIP, XIAP, and cIAP1 and 2, showed differential expression in the 2 cell lines. Western blot demonstrated complete cisplatin mediated suppression of c-FLIP expression in T24 cells but no change in c-FLIP expression was observed in T24R2 cells after cisplatin treatment in the same dose range. Suppression of c-FLIP expression in T24R2 cells by siRNA transfection rendered these cells significantly more sensitive to cisplatin treatment than untransfected T24R2 cells (p <0.05). CONCLUSIONS: Results reveal that c-FLIP has an important role in the cisplatin resistance of human bladder cancer cells and c-FLIP modulation may at least partially reverse cisplatin resistance in bladder cancer cells.

Pazopanib in Locally Advanced or Metastatic Renal Cell Carcinoma: Results of a Randomized Phase III Trial.

PURPOSE: Pazopanib is an oral angiogenesis inhibitor targeting vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and c-Kit. This randomized, double-blind, placebo-controlled phase III study evaluated efficacy and safety of pazopanib monotherapy in treatment-naive and cytokine-pretreated patients with advanced renal cell carcinoma (RCC). PATIENTS AND METHODS: Adult patients with measurable, locally advanced, and/or metastatic RCC were randomly assigned 2:1 to receive oral pazopanib or placebo. The primary end point was progression-free survival (PFS). Secondary end points included overall survival, tumor response rate (Response Evaluation Criteria in Solid Tumors), and safety. Radiographic assessments of tumors were independently reviewed. RESULTS: Of 435 patients enrolled, 233 were treatment naive (54%) and 202 were cytokine pretreated (46%). PFS was significantly prolonged with pazopanib compared with placebo in the overall study population (median, PFS 9.2 v 4.2 months; hazard ratio [HR], 0.46; 95% CI, 0.34 to 0.62; P < .0001), the treatment-naive subpopulation (median PFS 11.1 v 2.8 months; HR, 0.40; 95% CI, 0.27 to 0.60; P < .0001), and the cytokine-pretreated subpopulation (median PFS, 7.4 v 4.2 months; HR, 0.54; 95% CI, 0.35 to 0.84; P < .001). The objective response rate was 30% with pazopanib compared with 3% with placebo (P < .001). The median duration of response was longer than 1 year. The most common adverse events were diarrhea, hypertension, hair color changes, nausea, anorexia, and vomiting. There was no evidence of clinically important differences in quality of life for pazopanib versus placebo. CONCLUSION: Pazopanib demonstrated significant improvement in PFS and tumor response compared with placebo in treatment-naive and cytokine-pretreated patients with advanced and/or metastatic RCC.

Gender-specific clinicopathological features and survival in patients with renal cell carcinoma (RCC).

UNLABELLED: There has been some controversy about the gender differences in survival in patients with RCC. Korean women with RCC had a lower proportion of clear cell histology and a higher proportion of chromophobe histology. This histological difference might have driven the better survival rates in Korean women. OBJECTIVE: To assess whether there are gender-specific differences in the clinicopathological features and prognosis in a large cohort of Korean patients with renal cell carcinoma (RCC) compared with Western patients. PATIENTS AND METHODS: Medical records of 1616 patients clinically diagnosed with RCC who underwent partial or radical nephrectomy were analysed between January 1988 and July 2009. In all, 1508 patients diagnosed with RCC based on pathology reports were included for evaluation. The mean follow-up period was 73.1 months. The gender-specific differences in the clinicopathological features and survival rates were evaluated using the Kaplan-Meier method and Cox proportional hazards models. RESULTS: Of the 1508 patients, 439 (29.1%) were women. Korean men had a higher proportion of clear cell histology (84.3% vs 72.0%, P < 0.001) and a lower percentage of chromophobe histology (5.2% vs 12.5%, P < 0.001) than Korean women. There were no gender-specific differences in pathological T stage, positive lymph nodes or distant metastases, or Fuhrman's nuclear grade (P > 0.05). For both cancer-specific and overall survival, Kaplan-Meier curves showed that women had a better survival rate than men (P = 0.039 and P = 0.015, respectively). CONCLUSIONS: Korean women with RCC had significantly better survival rates than Korean men. Additionally, Korean women with RCC had a lower proportion of clear cell histology and a higher proportion of chromophobe histology. This histological difference might have driven the better survival rates in Korean women.

Percent tumor volume predicts biochemical recurrence after radical prostatectomy: multi-institutional data analysis.

BACKGROUND: To investigate the prognostic significance of percent tumor volume (PTV) in relation to the surgical margin status in men with prostate cancer after radical prostatectomy (RP). METHODS: Clinical and pathological data from 1,567 patients treated with RP only between 1995 and 2007 at participating institutions were reviewed. PTV was determined by the sum of all visually estimated tumor foci on every section. Biochemical recurrence (BCR) was defined as 2 consecutive increases in prostate-specific antigen (PSA) > 0.2 ng/ml and various clinicopathological variables were tested for prognostication of recurrence-free survival. RESULTS: Serum PSA at surgery was 12.5 ± 16.8 ng/ml and pathological stage was T2 in 899 (57.4%) patients. Surgical Gleason score was 7 in 842 patients (53.7%), higher than 7 in 250 (16%) patients, and in 32% of the patients, surgical margin was positive. Mean PTV was 15.7% and demonstrated a significant positive correlation with serum PSA, all pathological variables and BCR. On multivariate analysis, preoperative PSA (p = 0.012), surgical Gleason score (p < 0.0001, HR 2.183, 95% CI 1.778-2.681), and PTV (≤5, 5.1-15, >15%; p < 0.0001, HR 1.393, 95% CI 1.183-1.641) were independently prognostic of recurrence-free survival. Pathological stage demonstrated a significant relationship with BCR but was not independently prognostic in the multivariate model. CONCLUSION: In men with prostate cancer, preoperative PSA, surgical Gleason score, and PTV are independent predictors of recurrence-free survival after RP.

Nomograms to predict the pathological stage of clinically localized prostate cancer in Korean men: comparison with western predictive tools using decision curve analysis.

OBJECTIVES: To develop and evaluate nomograms to predict the pathological stage of clinically localized prostate cancer after radical prostatectomy in Korean men. METHODS: We reviewed the medical records of 2041 patients who had clinical stages T1c-T3a prostate cancer and were treated solely with radical prostatectomy at two hospitals. Logistic regressions were carried out to predict organ-confined disease, extraprostatic extension, seminal vesicle invasion, and lymph node metastasis using preoperative variables and resulting nomograms. Internal validations were assessed using the area under the receiver operating characteristic curve and calibration plot, and then external validations were carried out on 129 patients from another hospital. Head-to-head comparisons with 2007 Partin tables and Cancer of the Prostate Risk Assessment score were carried out using the area under the curve and decision curve analysis. RESULTS: The significant predictors for organ-confined disease and extraprostatic extension were clinical stage, prostate-specific antigen, Gleason score and a percent positive core of biopsy. Significant predictors for seminal vesicle invasion were prostate-specific antigen, Gleason score and percent positive core, and those for lymph node metastasis were prostate-specific antigen and percent positive core. The area under the curve of established nomograms for organ-confined disease, extraprostatic extension, seminal vesicle invasion and lymph node metastasis were 0.809, 0.804, 0.889 and 0.838, respectively. The nomograms were well calibrated and externally validated. These nomograms showed significantly higher accuracies and net benefits than two Western tools in Korean men. CONCLUSION: This is the first study to have developed and fully validated nomograms to predict the pathological stage of prostate cancer in an Asian population. These nomograms might be more accurate and useful for Korean men than other predictive models developed using Western populations.

The Relationship between Children's School Adaptation, Academic Achievement, Happiness, and Problematic Smartphone Usage: A Multiple Informant Moderated Mediating Model.

The school environment is a primary realm of life for school-aged children and thus their adaptation to school and academic performance may affect their degree of happiness. The age of smartphone users has declined, and problematic smartphone usage has widely expanded such that young children are also affected by such devices. This study assessed adaptation to school, academic achievement, problematic smartphone usage, and general happiness in a panel data sample of 695 Korean 10-year-old children and their teachers and mothers, and a moderated mediation model of these variables was tested. Results revealed that school adaptation affected general happiness of children through academic performance, and problematic smartphone usage demonstrated significant moderating effects on the relationship between school adaptation and academic achievement. Specifically, in children with a high level of adaptation to school life, the difference in problematic smartphone usage did not affect academic performance. However, lower level of adaptation led to greater differences in academic performance depending on problematic smartphone usage, and children with high problematic smartphone usage showed poorer academic performance. This study is meaningful because variables related to adaptation of 10-year-old children were collected from multiple informants. In addition, this study focused on general happiness, a positive factor, as the outcome variable to test the effects of variables related to school and problematic smartphone usage. Limitations include that a causal relationship cannot be examined, and qualitative differences in smartphone usage were not measured. Supplementary Information: The online version contains supplementary material available at 10.1007/s11482-022-10080-w.

Prognostic value of body mass index in Korean patients with renal cell carcinoma.

PURPOSE: Whether body mass index is a prognostic factor in patients with renal cell carcinoma continues to be debated. We investigated the association between body mass index, and clinical/pathological features and prognosis in a large cohort of Korean patients with renal cell carcinoma. MATERIALS AND METHODS: The medical records of 1,017 patients with renal cell carcinoma who underwent curative surgery between 1988 and 2006 were reviewed. Mean followup was 76.9 months. We analyzed the association of body mass index at surgery with tumor pathological features, and its associations with cancer specific survival and overall survival were evaluated using the Kaplan-Meier method and Cox regression models. Additional survival analysis was performed in a subgroup of 897 patients with T1-4N0M0 disease. RESULTS: Of the 1,017 patients 363 (35.7%), 526 (51.7%) and 128 (12.6%) had a body mass index of less than 23 (normal), 23 to 27.5 (overweight) and 27.5 or greater (obese) kg/m(2), respectively. Overweight and obese patients had less aggressive tumors, such as less lymph node and/or distant metastases (p = 0.001), low pathological T stage (p = 0.047) and low Fuhrman grade (p = 0.033) vs normal weight patients. In terms of cancer specific survival and overall survival multivariate analysis showed that overweight (p = 0.040 and p = 0.047, respectively) and obese (p = 0.024 and p = 0.010, respectively) patients had good survival rates compared to those with a body mass index in the normal range in the cohort (T1-4NallMall) groups. In addition, overweight (p = 0.022 and p = 0.029, respectively) and obese (p = 0.009 and p = 0.002, respectively) status was significantly associated with cancer specific and overall survival in the T1-4N0M0 groups. CONCLUSIONS: Our findings suggest that overweight and obese Korean patients with renal cell carcinoma have more favorable pathological features and a better prognosis than those with a normal body mass index.

Long-term oncologic outcomes after radical prostatectomy in clinically localized prostate cancer: 10-year follow-up in Korea.

Purpose: The clinical behavior of prostate cancer differs by race and ethnicity; however, data on the Korean population are scarce. We assessed the long-term oncologic outcomes of clinically localized prostate cancer after radical prostatectomy in Korean men. Materials and Methods: We analyzed 786 clinically localized prostate cancer patients who underwent radical prostatectomy, from June 1993 to June 2008. Kaplan-Meier survival curve analysis and log-rank test were used to assess the oncologic outcomes. Results: The mean age of the patients was 64.9±6.6 years. Pelvic lymph node dissection was performed in 373 patients. Pathologic T and N stage cancer with local advancement and invasion were detected by radical prostatectomy in 307 and 22 patients, respectively. In total, 38 patients who underwent adjuvant therapy were excluded from the analysis of progression after biochemical recurrence (BCR), which occurred in 261 men. In total, 219 patients underwent salvage treatment. Local recurrence and distant metastasis occurred in 109 and 42 patients, respectively; 36 patients experienced metastasis with local recurrence. Castration-resistant prostate cancer developed in 22 patients, and overall and disease-specific mortality was noted in 148 and 23 patients, respectively. The median duration from operation to BCR, BCR to metastasis, and metastasis to disease-specific death was 25, 40, and 22 months, respectively. Conclusions: We demonstrated the long-term prognosis of localized prostate cancer after radical prostatectomy among Koreans. Our results differ from those reported in the Western literature, with a lower prevalence of distant metastasis and shorter time to metastasis after BCR.

Reevaluation of renal cell carcinoma and perirenal fat invasion only.

PURPOSE: Controversy continues over whether perirenal fat invasion in pT3a renal cell carcinoma is a prognostic factor. We investigated the prognosis of renal cell carcinoma with perirenal fat invasion compared to the prognosis of other pathological stages by tumor size. MATERIALS AND METHODS: We reviewed the medical records of 946 patients who underwent curative surgery for pT1-pT3bN0M0 renal cell carcinoma between 1988 and 2006. Patients with pT3a stage disease and perirenal fat invasion only were divided into 2 subgroups by a 7 cm tumor size cutoff. The prognostic impact of perirenal fat invasion on disease-free and cancer specific survival was investigated. RESULTS: Patients with perirenal fat invasion and lesions greater than 7 cm had lower 5-year disease-free (49.5% vs 77.2%, p = 0.004) and cancer specific (58.5% vs 95.6%, p = 0.003) survival than those with lesions 7 cm or less. Patients with perirenal fat invasion and lesions 7 cm or less had similar 5-year disease-free and cancer specific survival compared to those with pT1 tumors (p = 0.109 and 0.602, respectively). For tumors 7 cm or less multivariate analysis showed that perirenal fat invasion was not a significant predictor of disease-free (p = 0.119) or cancer specific (p = 0.208) survival. In contrast, perirenal fat invasion was an independent prognostic factor for disease-free (p = 0.002) and cancer specific (p = 0.027) survival in patients with tumors greater than 7 cm. CONCLUSIONS: Findings suggest that the prognostic significance of perirenal fat invasion depends on primary tumor size. Perirenal fat invasion included in the pT3a stage regardless of tumor size should be reevaluated by tumor size for a more accurate patient prognosis.

Perineural invasion is a prognostic factor for biochemical failure after radical prostatectomy.

OBJECTIVES: To identify the prognostic significance of lymphovascular invasion (LVI) and perineural invasion (PNI) in patients undergoing radical prostatectomy for prostate cancer. METHODS: Overall, 237 patients who had undergone radical prostatectomy for prostate cancer between 1995 and 2004 were analyzed for all clinical and pathological factors. The influence of these two pathological features on biochemical failure-free survival was evaluated by univariate and multivariate analysis. RESULTS: Lymphovascular and perineural invasion were identified in 41 (17.2%) and 100 (42.0%) patients, respectively. LVI and PNI were significantly associated with the preoperative prostate-specific antigen (PSA) level, a higher PSA density, a higher pathological stage, a higher Gleason score, a higher frequency of extracapsular extension, a higher frequency of seminal vesicle invasion, and a higher frequency of a positive resection margin. Positive resection margins (P = 0.001) and perineural invasion (P = 0.011) were identified as independent factors associated with biochemical failure-free survival by the multivariate analysis. CONCLUSIONS: In this series, PNI was associated with established parameters of biologically aggressive disease, and was an important prognostic factor for biochemical failure-free survival in patients undergoing radical prostatectomy. This finding supports routine evaluation of the PNI status in radical prostatectomy specimens and suggests that patients with PNI should be more closely followed after surgery.

Analysis of resistance-associated gene expression in docetaxel-resistant prostate cancer cells.

Docetaxel-based chemotherapy is the standard treatment for metastatic castration-resistant prostate cancer (CRPC). However, a number of patients with metastatic CRPC are refractory to docetaxel or develop docetaxel resistance. The underlying molecular mechanisms of docetaxel resistance remain unclear, which is a significant burden to the management of metastatic prostate cancer. In the present study, the differential gene expression between docetaxel-sensitive (PC3) and docetaxel-resistant (PC3DR2) prostate cancer cells was identified using DNA microarrays, western blot analysis and reverse transcription-quantitative polymerase chain reaction. Of the genes implicated in cancer-associated pathways, insulin-like growth factor 1 receptor, DBF4 homolog, sterile α motif and leucine zipper-containing kinase AZK, Patched 1, serpin peptidase inhibitor, clade E, member 1 and breast cancer 2 (BRCA2) were >3-fold upregulated in PC3DR2 cells compared with PC3 cells. BRCA2 knockdown with small interfering RNA decreased the docetaxel resistance of PC3DR2 cells. These results suggest that BRCA2 serves an important role in the docetaxel resistance of prostate cancer cells. In addition, BRCA2 modulation may be a strategy to partially reverse docetaxel resistance in prostate cancer.

Upregulated expression of BCL2, MCM7, and CCNE1 indicate cisplatin-resistance in the set of two human bladder cancer cell lines: T24 cisplatin sensitive and T24R2 cisplatin resistant bladder cancer cell lines.

PURPOSE: The mechanism of resistance to cisplatin during treatment of bladder cancer (BC) has been a subject of intense investigation in clinical research. This study aims to identify candidate genes associated with resistance to cisplatin, in order to understand the resistance mechanism of BC cells to the drug, by combining the use of microarray profiling, quantitative reverse transcription-polymerase chain reaction (RT-PCR), and Western blot analyses. MATERIALS AND METHODS: The cisplatin sensitive human BC cell line (T24) and the cisplatin resistant BC cell line, T24R2, were used for microarray analysis to determine the differential expression of genes that are significant in cisplatin resistance. Candidate upregulated genes belonging to three well-known cancer-related KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways (p53 tumor suppressor, apoptosis, and cell cycle) were selected from the microarray data. These candidate genes, differentially expressed in T24 and T24R2, were then confirmed by quantitative RT-PCR and western blot. A fold change ≥2 with a p-value <0.05 was considered significant. RESULTS: A total of 18 significantly upregulated genes were detected in the three selected cancer-related pathways in both microarray and RT-PCR analyses. These genes were PRKAR2A, PRKAR2B, CYCS, BCL2, BIRC3, DFFB, CASP6, CDK6, CCNE1, STEAP3, MCM7, ORC2, ORC5, ANAPC1, and ANAPC7, CDC7, CDC27, and SKP1. Western blot analyses also confirmed the upregulation of BCL2, MCM7, and CCNE1 at the protein level, indicating their crucial association with cisplatin resistance. CONCLUSIONS: The BCL2, MCM7, and CCNE1 genes might play distinctive roles in cisplatin resistance in BC.

Effect of preoperative urodynamic detrusor overactivity on post-prostatectomy incontinence: a systematic review and meta-analysis.

PURPOSE: To investigate whether preoperative urodynamic detrusor overactivity (DO) contributes to post-prostatectomy incontinence (PPI). METHODS: We systematically searched the online PubMed, Embase, and Cochrane Library databases spanning the period of January 1989 to December 2014. RESULTS: A total of nine articles met the eligibility criteria for this systematic review. The eligible studies included a total of 457 patients with a median number of 58 patients per study (range 17-92). Of the nine studies, five conducted open retropubic radical prostatectomy (RRP), two performed robot-assisted laparoscopic prostatectomy (RALP), and two others utilized multiple modalities. PPI was more likely to occur in patients with preoperative DO [pooled odds ratio (OR) 2.30; 95 % confidence interval (CI) 1.39-3.82; studies 9; participants 419], as compared to patients who were DO negative. Sensitivity analysis using the subgroups of RRP (OR 2.32; 95 % CI 1.11-4.85), RALP (OR 3.41; 95 % CI 1.55-7.47), DO defined as any amplitude of involuntary contraction (OR 2.32; 95 % CI 1.11-4.85), no postoperative intervention (OR 2.32; 95 % CI 1.11-4.85), and outcome evaluation after 6 months (OR 2.32; 95 % CI 1.11-4.85) demonstrated consistent results. Although some comparisons showed inter-study heterogeneity, there was no clear evidence of publication bias in this meta-analysis. CONCLUSIONS: Our meta-analysis results suggest that preoperative DO is another possible underlying mechanism for PPI.

The establishment of KORCC (KOrean Renal Cell Carcinoma) database.

PURPOSE: The purpose of this article is to report establishment of the 1st Web-based database (DB) system to collect renal cell carcinoma (RCC) data in Korea. MATERIALS AND METHODS: The new Web-based DB system was established to collect basic demographic and clinicopahtological characteristics of a large cohort of patients with RCC in Korea. Data from a total of 6,849 patients were collected from 8 tertiary care hospitals that agreed to participate in organizing the Korean Renal Cell Carcinoma (KORCC) study group as of 1 July 2015. Basic demographic and clinicopathological characteristics were collected. The data of patients who underwent surgical treatments were analyzed to characterize Korean RCC. RESULTS: We established the 1st Web-based DB of Korean RCC, a database comprising renal mass management cases from multiple centers in Korea. The data of 5,281 patients who underwent surgical management (mean follow-up, 32 months) were analyzed. The most common symptom was incidentally detected renal mass (76.9%). Clinical T1a was the most common (54.3%) stage and mean tumor size was 4.8±4.2 cm. Radical nephrectomy accounted for 62.7% of cases and an open approach was used in 50.7% and 52.2% of radical and partial nephrectomies, respectively. The 5-year overall, cancer-specific and recurrence-free survival rates were 88.1%, 92.2%, and 88.0%, respectively. CONCLUSIONS: We report the 1st establishment of a Web-based DB system to collect RCC data in Korea. This DB system will provide a solid basis for the characterization of Korean RCC.

Solitary squamous cell carcinoma in the kidney after metachronous development of esophageal and lung cancer.

Solitary metastatic renal tumors are rarely encountered clinically. We report the case of a 65-year-old man who developed a solitary renal metastasis after undergoing an esophagectomy for esophageal cancer and subsequent lobectomy for lung cancer. The present case serves to demonstrate that careful follow-up is needed for esophageal cancer patients with cancer of another organ.

Predictive and Prognostic Value of Ribonucleotide Reductase Regulatory Subunit M1 and Excision Repair Cross-Complementation Group 1 in Advanced Urothelial Carcinoma (UC) Treated with First-Line Gemcitabine Plus Platinum Combination Chemotherapy.

Preclinical and clinical studies have suggested that expression of ribonucleotide reductase regulatory subunit M1 (RRM1) and excision repair cross-complementation group 1 (ERCC1) is associated with resistance to gemcitabine and cisplatin, respectively. We evaluated the significance of RRM1 and ERCC1 expression to predict tumor response to gemcitabine plus platinum chemotherapy (GP) and survival in advanced UC. We retrospectively collected tumor samples and reviewed clinical data of 53 patients with unresectable or metastatic UC, who were treated with first-line GP. RRM1 and ERCC1 expression were measured by immunohistochemistry. Among 53 patients, 12 (22.6%) and 26 (49.1%) patients had tumors that demonstrated a high expression for RRM1 and ERCC1, respectively. Twenty-nine (70.7%) of 41 patients with low RRM1 expression achieved a clinical response (complete + partial responses), but only 3 (25.0%) of 12 patients with high RRM1 expression achieved a clinical response after GP (P=0.007). Nineteen (70.4%) of 27 patients with low ERCC1 expression achieved a clinical response, while 13 (50.0%) of 26 patients with high ERCC1 expression achieved a clinical response (P=0.130). High RRM1 expression was associated with shorter progression free survival and overall survival (PFS P=0.006, OS P=0.006). Multivariate analysis confirmed that patients with high RRM1 expression had a significantly greater risk of progression and death than those with low RRM1 expression. ERCC1 status was not a significant predictor for PFS and OS. RRM1 expression was predictive and prognostic of clinical outcome in advanced UC treated with gemcitabine plus platinum combination chemotherapy.