Radiotherapy plus chemotherapy versus chemotherapy alone in penile cancer patients with extracapsular nodal extension after inguinal lymph node surgery: a multi-institutional study.

PURPOSE: Because there is a lack of evidence, it is not generally recommended to use adjuvant radiotherapy plus chemotherapy to treat lymph node disease in penile cancer. The aim of this study was to determine the benefit of using adjuvant radiotherapy after inguinal surgery for penile cancer. METHODS: Multi-institutional data were obtained from a total of nine centers from April 2003 to April 2015 and retrospectively analyzed. pN3 patients with an extracapsular nodal extension who received adjuvant therapy after inguinal surgery were included. Cancer-specific survival (CSS) was estimated using the Kaplan-Meier method. The multivariate analysis was performed using a Cox proportional hazards model. RESULTS: A total of 93 pN3 patients met the inclusion criteria. During the study period, 32 (34.4%) and 61 (65.6%) of these patients received adjuvant radiotherapy plus chemotherapy (AR + AC) or adjuvant chemotherapy alone (AC). The median CSS in all patients was 12.0 months (interquartile range [IQR] 7.5-16.5). The Kaplan-Meier estimated 3-year CSS rate was significantly longer in the AR + AC group (28.5%) than the AC group (16.2%) (p = 0.036). AC + AR was associated with an improvement in CSS by 7.7 months (17.7 [IQR 3.8-31.6] vs. 10.0 [IQR 6.6-13.4] months). In the Cox regression analysis, AR + AC was an independent predictor of CSS [model a: HR 0.486 (95% CI 0.258-0.916), model b: HR 0.527 (95% CI 0.286-0.972)]. CONCLUSION: In conclusions, AR + AC was associated with improved CCS in patients with penile cancer who displayed an extracapsular nodal extension after inguinal surgery. This hypothesis requires further confirmation.

Predictive value of single-nucleotide polymorphism signature for recurrence in localised renal cell carcinoma: a retrospective analysis and multicentre validation study.

BACKGROUND: Identification of high-risk localised renal cell carcinoma is key for the selection of patients for adjuvant treatment who are at truly higher risk of reccurrence. We developed a classifier based on single-nucleotide polymorphisms (SNPs) to improve the predictive accuracy for renal cell carcinoma recurrence and investigated whether intratumour heterogeneity affected the precision of the classifier. METHODS: In this retrospective analysis and multicentre validation study, we used paraffin-embedded specimens from the training set of 227 patients from Sun Yat-sen University (Guangzhou, Guangdong, China) with localised clear cell renal cell carcinoma to examine 44 potential recurrence-associated SNPs, which were identified by exploratory bioinformatics analyses of a genome-wide association study from The Cancer Genome Atlas (TCGA) Kidney Renal Clear Cell Carcinoma (KIRC) dataset (n=114, 906 600 SNPs). We developed a six-SNP-based classifier by use of LASSO Cox regression, based on the association between SNP status and patients' recurrence-free survival. Intratumour heterogeneity was investigated from two other regions within the same tumours in the training set. The six-SNP-based classifier was validated in the internal testing set (n=226), the independent validation set (Chinese multicentre study; 428 patients treated between Jan 1, 2004 and Dec 31, 2012, at three hospitals in China), and TCGA set (441 retrospectively identified patients who underwent resection between 1998 and 2010 for localised clear cell renal cell carcinoma in the USA). The main outcome was recurrence-free survival; the secondary outcome was overall survival. FINDINGS: Although intratumour heterogeneity was found in 48 (23%) of 206 cases in the internal testing set with complete SNP information, the predictive accuracy of the six-SNP-based classifier was similar in the three different regions of the training set (areas under the curve [AUC] at 5 years: 0·749 [95% CI 0·660-0·826] in region 1, 0·734 [0·651-0·814] in region 2, and 0·736 [0·649-0·824] in region 3). The six-SNP-based classifier precisely predicted recurrence-free survival of patients in three validation sets (hazard ratio [HR] 5·32 [95% CI 2·81-10·07] in the internal testing set, 5·39 [3·38-8·59] in the independent validation set, and 4·62 [2·48-8·61] in the TCGA set; all p<0·0001), independently of patient age or sex and tumour stage, grade, or necrosis. The classifier and the clinicopathological risk factors (tumour stage, grade, and necrosis) were combined to construct a nomogram, which had a predictive accuracy significantly higher than that of each variable alone (AUC at 5 years 0·811 [95% CI 0·756-0·861]). INTERPRETATION: Our six-SNP-based classifier could be a practical and reliable predictor that can complement the existing staging system for prediction of localised renal cell carcinoma recurrence after surgery, which might enable physicians to make more informed treatment decisions about adjuvant therapy. Intratumour heterogeneity does not seem to hamper the accuracy of the six-SNP-based classifier as a reliable predictor of recurrence. The classifier has the potential to guide treatment decisions for patients at differing risks of recurrence. FUNDING: National Key Research and Development Program of China, National Natural Science Foundation of China, Guangdong Provincial Science and Technology Foundation of China, and Guangzhou Science and Technology Foundation of China.

Correction to: Prognostic Role of the Immunoscore for Patients with Urothelial Carcinoma of the Bladder Who Underwent Radical Cystectomy.

In the original article, the word IMMUNOSCORE® was not displayed to reflect its trademark status. At every mention, IMMUNOSCORE® should be in all caps and with a registered trademark symbol.

Prognostic Role of the Immunoscore for Patients with Urothelial Carcinoma of the Bladder Who Underwent Radical Cystectomy.

BACKGROUND: Increasing evidence suggests that cancer progression is strongly influenced by the host immune response, which is represented by immune cell infiltrates. The T-lymphocyte-based Immunoscore is reported to be a reliable prognostic factor in colon cancer, but its significance in urothelial carcinoma of the bladder (UCB) is at an early stage of exploration. This study aimed to determine whether the tumor immune infiltrate, as evaluated by the Immunoscore, could act as a useful prognostic marker for UCB patients who have undergone radical cystectomy (RC). METHODS: In this study, immunohistochemistry was used to examine the Immunoscore of 221 UCB patients who underwent RC. The Immunoscore of the patients was determined by the densities of CD3+ and CD8+ T cells at the tumor center and the invasive margin. RESULTS: A highly significant association between a low Immunoscore and a shortened patient survival (P < 0.001, log-rank test) was demonstrated. In different subsets of UCB patients, a low Immunoscore also was a prognostic indicator of pT ≤ 2, pN(-)-status tumors, negative vascular invasion, or both (P < 0.05). Importantly, the Immunoscore together with the patient's pT status provided significant independent prognostic parameters in the multivariate analysis (P < 0.05). Furthermore, a significant correlation (P = 0.003) of a low Immunoscore with an increased UCB labeling index of Ki-67 (a cell proliferation marker) was observed in this UCB cohort. CONCLUSIONS: The findings suggest that the Immunoscore, as examined by immunohistochemistry, might serve as a novel prognostic marker for UCB patients who have undergone RC.

Relapse in children with clinical stage I testicular yolk sac tumors after initial orchiectomy.

PURPOSE: To evaluate risk factors of relapse in pediatric patients with clinical stage I (CS1) testicular yolk sac tumors. METHODS: With retrospective analysis, the medical records of children with pure testicular yolk sac tumors who were referred to Sun Yat-sen University Cancer Center and The First Affiliated Hospital from January 1995 to December 2015 were selected and recorded. Histopathology and staging were retrieved and multivariate analysis was performed with SPSS 20.0 software. RESULTS: 90 children with CS1 testicular yolk sac tumors were selected, and 21 of them underwent chemotherapy following initial orchiectomy. The median age of them was 17 months. With a median follow-up of 61 months (range 11-183 months), 84 patients were alive and 3 patients died, whereas the status was unknown in 3 patients. 30 patients experienced relapse within a median time of 4 months, including only 1 patient who underwent primary chemotherapy, and 28 of these patients underwent salvage chemotherapy. According to adjusted analysis, lymphovascular invasion (LVI) (P < 0.001), necrosis (P = 0.003) and primary chemotherapy (P = 0.008) were independent predictors of event-free survival. The 4-year event-free survival of high- and low-risk patients was 46.5% and 85.1%, respectively (P < 0.001). CONCLUSIONS: LVI and necrosis were independent risk factors for relapse in pediatric patients with CS1 testicular yolk sac tumors, and primary chemotherapy was effective. Thus, individualized management might be feasible for these patients according to risk classification.

[Incidence and Prognosis of Infections in the Elderly and Non-elderly Residents in a Community of Beijing].

Objective To compare the incidence and prognosis of infections between elderly and non-elderly residents in a community of Beijing. Method Adult inpatients during the study period(from July 1,2012 to June 30,2014)living in Yuetan Subdistrict of Beijing were screened for infections,and patients with infections were included into the analysis. Results A total of 19 472 patients were screened,and infections were found in 3449 patients(17.7%).The incidence was significantly higher in the elderly than that in the non-elderly patients(21.5%vs.10.5%,χ 2=362.202,P<0.001).Lower respiratory tract was the most commonly affected site,followed by genitourinary system.The mortalsity rate of the elderly patients with infections was significantly higher than that of the non-elderly patients with infections(13.6%vs.3.4%,χ 2=56.829,P<0.001)and increased with age.Logistic regression analysis found that older age,emergency surgery,comorbid cancer,chronic cardiac insufficiency,higher Charlson comorbidity index,intra-abdominal infection,gastrointestinal infection,bloodstream infection,lower respiratory infection,and hospital-acquired infection were independent risk factors of death for the elderly patients. Conclusion The incidence of infections in the elderly patients living in Yuetan Subdistrict of Beijing is much higher than that of the non-elderly patients,and elderly infected patients had longer hospital length of stays and higher mortality rates than non-elderly infected patients.

Efficacy and safety of first-line sunitinib in Chinese patients with metastatic renal cell carcinoma.

AIM: We report the first prospective study of sunitinib for metastatic renal cell carcinoma (mRCC) in China. METHODS: Chinese mRCC patients received first-line sunitinib 50 mg daily (4/2 regimen). Overall survival (OS), progression-free survival (PFS), objective response rate and safety were assessed. Potential efficacy biomarkers were explored in post hoc analyses. RESULTS: Median PFS was 61.7 weeks; median OS was 133.4 weeks; objective response rate was 31.1%. Most frequent adverse events (AEs) were: hand-foot syndrome (63.8%), decreased white blood cell count (52.4%), fatigue (51.4%) and decreased platelet count (51.4%). AEs were identified that predicted longer PFS and OS. CONCLUSION: Sunitinib showed efficacy and manageable AE profile in treatment-naive Chinese mRCC patients. Larger prospective studies are required to confirm identified AEs as predictors of efficacy.

[Independent external verification of the nomograms for predicting lymph node metastasis in penile cancer].

Objective: To evaluate the two newly established nomograms for predicting lymph node metastasis in penile cancer based on the clinical data on a large cohort of patients. METHODS: We retrospectively studied the clinical data on 93 patients with penile cancer treated in the Center for Tumor Prevention and Treatment. Using the two recently established nomograms (Bhagat nomogram and Zhu nomogram), we predicted lymph node metastasis in the patients, analyzed the differences between prediction and the results of postoperative pathology, and compared the accuracy of prediction between the two nomograms with the receiver operating characteristic (ROC) curve and the area under the curve (AUC). RESULTS: The median age of the patients was 55 (27－82) years. Positive lymph nodes were found in 31 cases (33.3%) postoperatively and in 9 (21.9%) of the 41 clinically negative cases. The AUC of the Bhagat nomogram was 0.739 and that of Zhu nomogram was 0.808, both of which were similar to the prediction accuracy of internal verification and manifested a medium predictive ability. CONCLUSIONS: The newly established Bhagat and Zhu nomograms can be used for predicting lymph node metastasis in penile cancer, but with a low precision, and therefore cannot be relied exclusively for the option of inguinal lymphadenectomy.

Chromobox homolog 8 is a predictor of muscle invasive bladder cancer and promotes cell proliferation by repressing the p53 pathway.

Chromobox homolog 8 (CBX8), also known as human polycomb 8, is a repressor that maintains the transcriptionally repressive state in various cellular genes, and has been reported to promote tumorigenesis. In the present study, we examined CBX8 expression in eight pairs of muscle invasive bladder cancer tissues and adjacent non-tumor tissues, and found that CBX8 was frequently upregulated in muscle invasive bladder cancer tissues when compared to adjacent non-tumor tissues. Analysis showed that high expression of CBX8 in 152 muscle invasive bladder cancer specimens was associated with progression of the T, N, and M stages (P = 0.004, 0.005, <0.001, respectively). Furthermore, Kaplan-Meier survival analysis and log-rank test showed that muscle invasive bladder cancer patients with high CBX8 expression had a poor rate of overall survival (P < 0.001) and 5-year recurrence-free survival (P < 0.001) compared to patients with low CBX8 expression. High CBX8 expression predicted poor overall survival and 5-year recurrence-free survival in T and N stages of muscle invasive bladder cancer patients. Moreover, knockdown of CBX8 inhibited cell proliferation of urothelial carcinoma of the bladder both in vitro and in vivo. In addition, CBX8 depletion resulted in cell cycle delay of urothelial carcinoma cells of the bladder at the G2/M phase by the p53 pathway. The data suggest that high expression of CBX8 plays a critical oncogenic role in aggressiveness of urothelial carcinoma cells of the bladder through promoting cancer cell proliferation by repressing the p53 pathway, and CBX8 could be used as a novel predictor for muscle invasive bladder cancer patients.

Trends of testis-sparing surgery for pediatric testicular tumors in South China.

BACKGROUND: Testis-sparing surgery is not popular in South China. This study aimed to investigate this procedure for pediatric testicular tumors. METHODS: Children with testicular benign tumors were retrospectively analyzed from January 2001 to June 2015 in the Sun Yat-sen University Cancer Center (SYSUCC) and the First Affiliated Hospital (SYSU-1st). Follow-up was performed until June 2016, and the proportions of TSS in the two hospitals during the different periods were compared. RESULTS: Forty-seven children with testicular benign tumors were enrolled, and 16 cases underwent testis-sparing surgery. All patients were cured and discharged, which included mature teratoma (n = 37), testicular adrenal rest tumors (n = 4), epidermal cysts (n = 3), granulomatous inflammation (n = 2) and adenomatoid tumors (n = 1). Inguinal testis-sparing surgery was performed in 16 children, and no recurrence was detected during follow-up. It was performed more frequently in SYSUCC than in SYSU-1st (P = 0.031), and the tumor size of these patients was smaller than those of patients who underwent radical orchiectomy (P = 0.044). Moreover, testis-sparing surgery has become more common in the past 5 years, although differences over time have not reached significance (P = 0.051). CONCLUSIONS: Testis-sparing surgery is reliable, and tumor size and special hospitals affect its success. Additionally, its use has become more popular in recent years. However, advocacy is still needed for the use of this technique in pediatric testicular benign tumors that are small sized.

Laparoscopic versus open nephroureterectomy to treat localized and/or locally advanced upper tract urothelial carcinoma: oncological outcomes from a multicenter study.

BACKGROUND: Many studies have reported the oncological outcomes between open radical nephroureterectomy (ONU) and laparoscopic radical nephroureterectomy (LNU) of upper tract urothelial carcinoma (UTUC). However, few data have focused on the oncological outcomes of LNU in the subgroup of localized and/or locally advanced UTUC (T1-4/N0-X). The purpose of this study was to compare the oncological outcomes of LNU vs. ONU for the treatment in patients with T1-4/N0-X UTUC. METHODS: We collected and analyzed the data and clinical outcomes retrospectively for 265 patients who underwent radical nephroureterectomy for T1-4/N0-X UTUC between April 2000 and April 2013 at two Chinese tertiary hospitals. Survival was estimated using the Kaplan-Meier method. Cox's proportional hazards model was used for univariate and multivariate analysis. RESULTS: The mean patient age was 62.0 years and the median follow-up was 60.0 months. Of the 265 patients, 213 (80.4%) underwent conventional ONU, and 52 (19.6%) patients underwent LNU. The groups differed significantly in their presence of previous hydronephrosis, presence of previous bladder urothelial carcinoma, and management of distal ureter (P < 0.05). The predicted 5-year intravesical recurrence- free survival (RFS) (79% vs. 88%, P = 0.204), overall RFS (47% vs. 59%, P = 0.076), cancer-specific survival (CSS) (63% vs. 70%, P = 0.186), and overall survival (OS) (61% vs. 55%, P = 0.908) rates did not differ between the ONU and LNU groups. Multivariable Cox proportional regression analysis showed that surgical approach was not significantly associated with intravesical RFS (odds ratio [OR] 1.23, 95% confidence interval [CI] 0.46-3.65, P = 0.622), Overall RFS (OR 0.99, 95% CI 0.54-1.83, P = 0.974), CSS (OR 1.38, 95% CI 0.616-3.13, P = 0.444), or OS (OR 1.61, 95% CI 0.81-3.17, P = 0.17). CONCLUSIONS: The results of this retrospective study showed no statistically significant differences in intravesical RFS, overall RFS, CSS, or OS between the laparoscopy and the open groups. Thus, LNU can be an alternative to the open procedure for T1-4/N0-X UTUC. Further studies, including a multi-institutional, prospective study are required to confirm these findings.

Clinical significance of preoperative C-reactive protein and squamous cell carcinoma antigen levels in patients with penile squamous cell carcinoma.

OBJECTIVE: To evaluate the relevance of C-reactive protein (CRP) and squamous cell carcinoma antigen (SCC-Ag) levels in relation to clinicopathological factors and prognosis in penile cancer. PATIENTS AND METHODS: A total of 124 Chinese patients with penile squamous cell carcinoma (SCC), treated between November 2007 and October 2014, were analysed retrospectively. Receiver-operating characteristic curves were used to identify the combination of markers with the best sensitivity and specificity for prognosis prediction. Statistical data analysis was performed using a non-parametric method, and survival analysis was performed using the log-rank test and Cox proportional hazard model. RESULTS: Levels of CRP ≥4.5 mg/L and SCC-Ag ≥1.4 ng/mL were both significantly associated with lymph node metastasis (LNM) laterality (chi-squared trend test, P = 0.041), extranodal extension (chi-squared trend test, P < 0.001), pelvic LNM (chi-squared trend test, P = 0.024), pathological tumour status (chi-squared trend test, P = 0.002), pathological nodal status (chi-squared trend test, P < 0.001), and disease-specific survival (DSS; log-rank test, P < 0.001). Moreover, the influence of CRP and SCC-Ag levels on DSS (P = 0.033, hazard ratio 3.390, 95% confidence interval 1.104-10.411) remained after adjusting for smoking history, phimosis, tumour status, tumour cell differentiation and nodal status. CONCLUSIONS: The present study shows that the combined measurement of preoperative CRP and SCC-Ag levels may serve as an independent biomarker for LNM, advanced tumour stage and DSS in patients with penile SCC.

The importance of extranodal extension in penile cancer: a meta-analysis.

BACKGROUND: The role of extranodal extension (ENE) in penile cancer is controversial and has not been well studied. The aim of this study was to investigate the importance of ENE in predicting prognosis and presence of pelvic lymph node metastasis (PLNM) in penile cancer patients. METHODS: We searched related studies in Medline, Embase, Cochrane Library, and Scopus database. Hazard ratio (HR) and odds ratio (OR) were directly extracted or indirectly estimated from the included studies. RESULTS: A total of ten studies with 1,142 patients were included in this meta-analysis. Patients with ENE showed a worse cancer-specific survival (CSS) (HR = 1.90, 95 % confidence interval [CI] = 1.35-2.67, P = 0.0002) and overall survival (HR = 4.04, 95 % CI = 1.02-16.1, P = 0.05) than those without ENE. Further subgroup analysis revealed that the predictive value of ENE for CSS in penile cancer patients was significant regardless of the study's country of origin, but not in the subgroup with shorter follow-up time (<36 months, P = 0.38). Patients with ENE also showed a higher incidence of presenting with PLNM (OR = 4.95, 95 % CI = 2.58-9.49, P < 0.001). A stratified analysis demonstrated that the predictive role of ENE for PLNM was only detected in studies with a larger sample size (> 100 cases). No significant publication bias was observed, as suggested by Begg's and Egger's tests. CONCLUSIONS: ENE is associated with worse prognosis and high risk of PLNM in penile cancer patients. Due to the limited number of studies included in this meta-analysis, a large-scale, well-designed study will be required to verify our results.

Tumor necrosis predicts poor clinical outcomes in patients with node-negative upper urinary tract urothelial carcinoma.

OBJECTIVE: Tumor necrosis has been indicated as a factor for the poor clinical outcome in human cancers. We aim to disclose the association between tumor necrosis and overall survival and recurrence-free survival in node-negative upper urinary tract urothelial carcinoma patients treated with radical nephroureterectomy. METHODS: A retrospective cohort of 100 patients with upper urinary tract urothelial carcinoma from January 1990 to June 2011 was enrolled in this study. Univariate analysis with Log-rank test and multivariate analysis with Cox proportional hazards regression models were conducted to determine the correlations of tumor necrosis with overall survival and recurrence-free survival. RESULTS: Tumor necrosis was presented in 48 patients with upper urinary tract urothelial carcinoma and was significantly associated with the advanced pathological stage (P < 0.001), high tumor grade (P < 0.001), subsequent bladder tumor (P = 0.018), vascular invasion (P < 0.001) and lymph node metastasis (P = 0.026). Multivariate analysis revealed tumor necrosis as an independent unfavorable predictor of overall survival in node-negative upper urinary tract urothelial carcinoma patients by multivariate analysis (hazard ratio = 9.23, 95% confidence interval = 1.05-80.89, P = 0.045). CONCLUSIONS: Tumor necrosis was an independent factor of adverse clinical outcomes in node-negative upper urinary tract urothelial carcinoma patients who received radical nephroureterectomy. Evaluation of tumor necrosis might be of clinical significance to determine whether patients with node-negative upper urinary tract urothelial carcinoma should be given further therapy after radical nephroureterectomy.

Influence of body mass index on oncological outcomes in patients with upper urinary tract urothelial carcinoma treated with radical nephroureterectomy.

OBJECTIVE: To investigate the association between body mass index and oncological outcomes in Chinese patients who had undergone radical nephroureterectomy for upper urinary tract urothelial carcinoma. METHODS: Between August 1998 and October 2009, 236 consecutive Chinese patients underwent radical nephroureterectomy for upper urinary tract urothelial carcinoma at Sun Yat-sen University Cancer Center (Guangzhou, China). Body mass index data were available for 230 (97.5%) of these patients. All 230 patients were classified into three groups according to the body mass index criteria for Asians, issued by the Asia Cohort Consortium: underweight, body mass index <18.5 kg/m(2) (n = 21, 9.1%); normal weight, body mass index ≥18.5 and <25 kg/m(2) (n = 151, 65.7%); and obesity, body mass index ≥25 kg/m(2), (n = 58, 25.2%). Spearman's rank correlation, Kaplan-Meier plots and Cox proportional hazards regression model were used to analyze the data. RESULTS: Being underweight was significantly associated with lymph node metastasis (P = 0.017) and Eastern Cooperative Oncology Group performance status (P = 0.003). Univariate analysis showed recurrence-free survival and cancer-specific survival were significantly worse in underweight patients than in patients with normal weight or obese patients. After adjustments for other clinicopathological variables, multivariate analysis confirmed that recurrence-free survival and cancer-specific survival were significantly worse in underweight patients than in patients with normal weight or obese patients (recurrence-free survival P = 0.014, cancer-specific survival P = 0.015). CONCLUSIONS: Preoperative underweight is an independent predictor of unfavorable recurrence-free survival and cancer-specific survival in Chinese patients with upper urinary tract urothelial carcinoma treated by radical nephroureterectomy, whereas obesity is associated with superior recurrence-free survival and cancer-specific survival. Further studies, including a multi-institutional, prospective, Asian cohort study, are required to confirm these findings.

Radical cystectomy for bladder cancer: oncologic outcome in 271 Chinese patients.

Few large scale studies have reported the oncologic outcome of radical cystectomy for treating bladder cancer in China; hence, we lack long-term prognostic information. The aim of the current study was to determine the survival rate and prognostic factors of patients who underwent radical cystectomy for bladder cancer in a Chinese medical center. We retrospectively analyzed clinicopathologic data from 271 bladder cancer patients who underwent radical cystectomy between 2000 and 2011. Univariate and multivariate analyses were conducted to identify independent prognostic predictors for this cohort. Median follow-up was 31.7 months (range, 0.2-139.1 months). Thirty-day mortality was (1.4%). The 5-year recurrence-free survival, cancer-specific survival (CSS), and overall survival rates were 61.6%, 72.9%, and 68.0%, respectively. The 5-year CSS rates of patients with T1-T4 disease were 90.7%, 85.0%, 51.0%, and 18.0%, respectively. Patients with organ-confined disease had a higher 5-year CSS rate than those with extravesical disease (81.4% vs. 34.9%, P < 0.001). For the 38 patients (14%) with lymph node involvement, the 5-year CSS rate was 27.7%-significantly lower than that of patients without lymph node metastasis (P < 0.001). The 5-year CSS rate was much higher in patients with low grade tumor than in those with high grade tumor (98.1% vs. 68.1%, P < 0.001). Multivariate Cox regression showed that patient age (hazard ratio, 2.045; P = 0.013) and T category (hazard ratio, 2.213; P < 0.001) were independent predictors for CSS. These results suggest that radical cystectomy is a safe and effective method for treating bladder cancer in Chinese patients. Old age and high T category were associated with poor prognosis in bladder cancer patients who underwent radical cystectomy.

PinX1 suppresses bladder urothelial carcinoma cell proliferation via the inhibition of telomerase activity and p16/cyclin D1 pathway.

BACKGROUND: PIN2/TRF1-interacting telomerase inhibitor1 (PinX1) was recently suggested as a putative tumor suppressor in several types of human cancer, based on its binding to and inhibition of telomerase. Moreover, loss of PinX1 has been detected in many human malignancies. However, the possible involvement of PinX1 and its clinical/prognostic significance in urothelial carcinoma of the bladder (UCB) are unclear. METHODS: The PinX1 expression profile was examined by quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, and immunohistochemistry (IHC) in UCB tissues and adjacent normal urothelial bladder epithelial tissues. PinX1 was overexpressed and silenced in UCB cell lines to determine its role in tumorigenesis, development of UCB, and the possible mechanism. RESULTS: PinX1 expression in UCB was significantly down-regulated at both mRNA and protein level as compared with that in normal urothelial bladder epithelial tissues. PinX1 levels were inversely correlated with tumor multiplicity, advanced N classification, high proliferation index (Ki-67), and poor survival (P < 0.05). Moreover, overexpression of PinX1 in UCB cells significantly inhibited cell proliferation in vitro and in vivo, whereas silencing PinX1 dramatically enhanced cell proliferation. Overexpression of PinX1 resulted in G1/S phase arrest and cell growth/proliferation inhibition, while silencing PinX1 led to acceleration of G1/S transition, and cell growth/proliferation promotion by inhibiting/enhancing telomerase activity and via the p16/cyclin D1 pathway. CONCLUSIONS: These findings suggest that down-regulation of PinX1 play an important role in the tumorigenesis and development of UCB and that the expression of PinX1 as detected by IHC is an independent molecular marker in patients with UCB.

Pericyte coverage of differentiated vessels inside tumor vasculature is an independent unfavorable prognostic factor for patients with clear cell renal cell carcinoma.

BACKGROUND: The objective of this study was to evaluate the effect of pericyte coverage (PC) of differentiated tumor microvessels on the prognosis of patients with clear cell renal cell carcinoma (CCRCC). METHODS: Samples from 2 cohorts of patients with CCRCC (101 Asian patients and 524 US patients) were prepared using 2 different histologic approaches: routine sectioning versus tissue microarray. Then, the samples were immunohistochemically doubled-stained for a pericyte marker (alpha smooth muscle actin [α-SMA]) and a differentiated vessel marker (cluster of differentiation 34 [CD34]), followed by multispectral image capturing and computerized image analyses to quantify the microvessel density (MVD) and the PC of differentiated vessels. The correlations of PC and the MVD:PC ratio with clinicopathologic characteristics were analyzed. RESULTS: There was an inverse correlation between differentiated MVD and PC. Higher PC correlated with more aggressive clinicopathologic characteristics of CCRCC in both cohorts, including more advanced T-classification, higher pathologic grades, and the occurrence of tumor necrosis. The MVD:PC ratio was an independent favorable prognostic factor for overall and recurrence-free survival in the Asian cohort and for recurrence-free survival in the US cohort. PC also was an independent prognostic factor, with higher PC predicting a poorer outcome. The combination of PC and MVD was better at distinguishing the outcome of patients with CCRCC. PC combined with differentiated MVD or with the MVD:PC ratio provided additional, independent prognostic information to the Leibovich risk model, and that information was used to generate improved risk models. CONCLUSIONS: The authors consistently observed that higher PC was correlated with more aggressive clinicopathologic characteristics. PC was an independent unfavorable prognostic factor. The authors concluded that pericytes should be considered for therapeutic targeting.

Overexpression of YAP 1 contributes to progressive features and poor prognosis of human urothelial carcinoma of the bladder.

BACKGROUND: Yes-associated protein 1 (YAP 1), the nuclear effector of the Hippo pathway, is a key regulator of organ size and a candidate human oncogene in multiple tumors. However, the expression dynamics of YAP 1 in urothelial carcinoma of the bladder (UCB) and its clinical/prognostic significance are unclear. METHODS: In this study, the methods of quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting and immunohistochemistry (IHC) were utilized to investigate mRNA/ protein expression of YAP 1 in UCBs. Spearman's rank correlation, Kaplan-Meier plots and Cox proportional hazards regression model were used to analyze the data. RESULTS: Up-regulated expression of YAP 1 mRNA and protein was observed in the majority of UCBs by qRT-PCR and Western blotting, when compared with their paired normal bladder tissues. By IHC, positive expression of YAP 1 was examined in 113/213 (53.1%) of UCBs and in 6/86 (7.0%) of normal bladder specimens tissues. Positive expression of YAP 1 was correlated with poorer differentiation, higher T classification and higher N classification (P < 0.05). In univariate survival analysis, a significant association between positive expression of YAP 1 and shortened patients' survival was found (P < 0.001). In different subsets of UCB patients, YAP 1 expression was also a prognostic indicator in patients with grade 2 (P = 0.005) or grade 3 (P = 0.046) UCB, and in patients in pT1 (P = 0.013), pT2-4 (P = 0.002), pN- (P < 0.001) or pT2-4/pN- (P = 0.004) stage. Importantly, YAP 1 expression (P = 0.003) together with pT and pN status (P< 0.05) provided significant independent prognostic parameters in multivariate analysis. CONCLUSIONS: Our findings provide evidences that positive expression of YAP 1 in UCB may be important in the acquisition of an aggressive phenotype, and it is an independent biomarker for poor prognosis of patients with UCB.

The risk factors for the presence of pelvic lymph node metastasis in penile squamous cell carcinoma patients with inguinal lymph node dissection.

OBJECTIVE: To evaluate factors in penile squamous cell carcinoma predictive of pelvic lymph node metastasis and survival. MATERIALS AND METHODS: Data were collected and analyzed retrospectively in 146 patients with squamous cell carcinoma of penis who underwent bilateral inguinal lymph node dissection in our center between January 1998 and April 2011. Variables recorded included serum squamous cell carcinoma antigen, primary tumor p53 immunoreactivity, histological grade, pathological tumor stage, lymphatic or vascular invasion, absent/unilateral or bilateral inguinal lymph node involvement, number of metastatic inguinal lymph nodes, presence of extracapsular growth and lymph node density. RESULTS: Seventy patients had inguinal lymph node metastasis (LNM). Of these, 33 (47.1%) had pelvic LNM. Primary tumor strong p53 expression, lymphatic or vascular invasion, involvement of more than two inguinal lymph nodes and 30% or greater lymph node density were significant predictors of pelvic LNM. Primary tumor strong p53 expression (odds ratio [OR] 5.997, 95% confidence intervals [CI] 1.615-22.275), presence of extracapsular growth (OR 2.209, 95% CI 1.166-4.184), involvement of more than two inguinal lymph nodes (OR 2.494, 95% CI 1.086-5.728) and pelvic lymph node involvement (OR 18.206, 95% CI 6.807-48.696) were independent prognostic factors for overall survival. CONCLUSIONS: Primary tumor expression of p53, lymphatic or vascular invasion, number of metastatic inguinal lymph nodes and lymph node density were all predictors of pathologic pelvic lymph node involvement. Patients with pelvic LNM had an adverse prognosis, with a 3-year overall survival rate of approximately 12.1%. Pelvic lymph node dissection should be considered in these cases.