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Supplementary Figure S1. CircPRMT5 is upregulated in UCB cells. Supplementary Figure S2. CircPRMT5 promotes migration and invasion of UCB cells. Supplementary Figure S3. CircPRMT5 contains multiple target sites of miRNAs. Supplementary Figure S4. CircPRMT5 promotes migration and invasion of UCB cells by reducing the inhibitory effect of miR-30c via sponge activity. Supplementary Figure S5. SNAIL1 is a target of miR-30c. Supplementary Figure S6. Representative images of SNAIL1 and E-cadherin expressions examined by IHC in UCB tissues with high (left) and low (right) expression of circPRMT5. Supplementary Figure S7. The correlation between expressions of SNAIL1 and miR-200 family in UCB tissues derived from TCGA database. Supplementary Figure S8. CircPRMT5 was secreted into exosomes derived from serum and urine of UCB patients. Supplementary Table S1. Correlation between expression of circPRMT5 and patients' clinicopathological variables in UCB patients Supplementary Table S2. The up-regulated and down-regulated circRNAs in UBCs Supplementary Table S3. Correlation of miR-30c expression with patients' clinicopathological variables in TCGA UCB cohorts Supplementary Table S4. Correlation of circPRMT5 expression in serum exosomes with patients' clinicopathological variables in 71 cases of UCB

Purpose: Circular RNAs (circRNAs), a novel class of noncoding RNAs, have recently drawn lots of attention in the pathogenesis of human cancers. However, the role of circRNAs in cancer cells epithelial–mesenchymal transition (EMT) remains unclear. In this study, we aimed to identify novel circRNAs that regulate urothelial carcinoma of the bladder (UCB) cells’ EMT and explored their regulatory mechanisms and clinical significance in UCBs.Experimental Design: We first screened circRNA expression profiles using a circRNA microarray in paired UCB and normal tissues, and then studied the clinical significance of an upregulated circRNA, circPRMT5, in a large cohort of patients with UCB. We further investigated the functions and underlying mechanisms of circPRMT5 in UCB cells’ EMT. Moreover, we evaluated the regulation effect of circPRMT5 on miR-30c, and its target genes, SNAIL1 and E-cadherin, in two independent cohorts from our institute and The Cancer Genome Atlas (TCGA).Results: We demonstrated that upregulated expression of circPRMT5 was positively associated with advanced clinical stage and worse survival in patients with UCB. We further revealed that circPRMT5 promoted UCB cell's EMT via sponging miR-30c. Clinical analysis from two independent UCB cohorts showed that the circPRMT5/miR-30c/SNAIL1/E-cadherin pathway was essential in supporting UCB progression. Importantly, we identified that circPRMT5 was upregulated in serum and urine exosomes from patients with UCB, and significantly correlated with tumor metastasis.Conclusions: CircPRMT5 exerts critical roles in promoting UCB cells’ EMT and/or aggressiveness and is a prognostic biomarker of the disease, suggesting that circPRMT5 may serve as an exploitable therapeutic target for patients with UCB.

Background Indoleamine 2,3‐dioxygenase 1 (IDO1) and tryptophan (Trp) catabolism have been demonstrated to play an important role in tumor immunosuppression. This study examined the expression and catalytic activity of IDO1 in penile squamous cell carcinoma (PSCC) and explored their clinical significance. Methods IDO1 expression level, serum concentrations of Trp and kynurenine (Kyn) were examined in 114 PSCC patients by immunohistonchemistry and solid‐phase extraction‐liquid chromatography‐tandem mass spectrometry. The survival was analyzed using Kaplan‐Meier method and the log‐rank test. Hazard ratio of death was analyzed via univariate and multivariate Cox regression. Immune cell types were defined by principal component analysis. The correlativity was assessed by Pearson's correlation analysis. Results The expression level of IDO1 in PSCC cells was positively correlated with serum Kyn concentration and Kyn/Trp radio (KTR; both P

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). 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. A highly significant association between a low Immunoscore and a shortened patient survival (P

Although 5-methylcytosine (m5C) is a widespread modification in RNAs, its regulation and biological role in pathological conditions (such as cancer) remain unknown. Here, we provide the single-nucleotide resolution landscape of messenger RNA m5C modifications in human urothelial carcinoma of the bladder (UCB). We identify numerous oncogene RNAs with hypermethylated m5C sites causally linked to their upregulation in UCBs and further demonstrate YBX1 as an m5C 'reader' recognizing m5C-modified mRNAs through the indole ring of W65 in its cold-shock domain. YBX1 maintains the stability of its target mRNA by recruiting ELAVL1. Moreover, NSUN2 and YBX1 are demonstrated to drive UCB pathogenesis by targeting the m5C methylation site in the HDGF 3' untranslated region. Clinically, a high coexpression of NUSN2, YBX1 and HDGF predicts the poorest survival. Our findings reveal an unprecedented mechanism of RNA m5C-regulated oncogene activation, providing a potential therapeutic strategy for UCB.

Purpose There are limited therapeutic options for patients with advanced penile squamous cell carcinoma (PSCC) after chemotherapy failure. Thus, we evaluated the feasibility of salvage treatment using the epidermal growth factor receptor (EGFR) mono-antibody nimotuzumab in chemotherapy-failed PSCC patients and explored potential response or resistance biomarkers. Materials and methods Six chemotherapy-failed PSCC patients with locally advanced disease or distant metastasis were enrolled consecutively to nimotuzumab treatment. Clinical responses and side effects were evaluated, and genetic characteristics of cancer specimens were analyzed through the next-generation sequencing of hotspot regions in cancer-related genes. Results Two of 6 patients showed partial responses, one was identified as having stable disease, while the other 3 had disease progression after nimotuzumab therapy. Side effects were all welltolerated. Genetic analysis revealed that TP53, CDKN2A, RB1, SMAD4, FLT3, and PIK3CA were the most frequently mutated genes in PSCC specimens, while altered KRAS, HRAS, EGFR, ERBB2, and FLT3 may be correlated with nimotuzumab resistance. Furthermore, 3 patients that were human papillomavirus-positive each showed clinical response or stable disease. Conclusions EGFR mono-antibody may be a potential modality for locally advanced PSCC patients after chemotherapy failure. Further large-scale clinical studies are needed to elucidate the role of human papillomavirus status and critical gene mutations in the clinical response to EGFR-targeted therapy.

Purpose: Circular RNAs (circRNAs), a novel class of noncoding RNAs, have recently drawn lots of attention in the pathogenesis of human cancers. However, the role of circRNAs in cancer cells epithelial–mesenchymal transition (EMT) remains unclear. In this study, we aimed to identify novel circRNAs that regulate urothelial carcinoma of the bladder (UCB) cells’ EMT and explored their regulatory mechanisms and clinical significance in UCBs. Experimental Design: We first screened circRNA expression profiles using a circRNA microarray in paired UCB and normal tissues, and then studied the clinical significance of an upregulated circRNA, circPRMT5, in a large cohort of patients with UCB. We further investigated the functions and underlying mechanisms of circPRMT5 in UCB cells’ EMT. Moreover, we evaluated the regulation effect of circPRMT5 on miR-30c, and its target genes, SNAIL1 and E-cadherin, in two independent cohorts from our institute and The Cancer Genome Atlas (TCGA). Results: We demonstrated that upregulated expression of circPRMT5 was positively associated with advanced clinical stage and worse survival in patients with UCB. We further revealed that circPRMT5 promoted UCB cell's EMT via sponging miR-30c. Clinical analysis from two independent UCB cohorts showed that the circPRMT5/miR-30c/SNAIL1/E-cadherin pathway was essential in supporting UCB progression. Importantly, we identified that circPRMT5 was upregulated in serum and urine exosomes from patients with UCB, and significantly correlated with tumor metastasis. Conclusions: CircPRMT5 exerts critical roles in promoting UCB cells’ EMT and/or aggressiveness and is a prognostic biomarker of the disease, suggesting that circPRMT5 may serve as an exploitable therapeutic target for patients with UCB.

Owing to the aggressive nature of radical nephroureterectomy (RNU), it is extremely important for the diagnostic modalities to be accurate. The European Association of Urology guidelines recommend that diagnostic ureteroscopy (URS) and biopsy be performed for upper urinary tract urothelial carcinomas (UUTCs). But that diagnostic URS adversely affects oncologic outcomes still exist. In the current systematic review and meta-analysis, we had attempted to evaluate oncologic outcome of diagnostic URS before RNU.All relevant articles were retrieved from PubMed, Embase, Web of Science, and the Cochrane Library. Endpoint events were recurrence-free survival, metastasis-free survival, cancer-specific survival, and overall survival.Compared with patients who underwent RNU alone, those who underwent diagnostic URS before RNU had significantly higher intravesical recurrence rate (HR = 1.42, 95% CI: 1.24-1.61, IDiagnostic URS before RNU does not seem to compromise long-term survival outcomes, even though it is associated with a higher rate of intravesical recurrence (IVR). Our findings suggest that further investigation, especially through prospective studies, should focus on decreasing the rate of IVR by administration of intravesical chemotherapy immediately after diagnostic URS.

Qiang-Hua Zhou,1,2,* Chuang-Zhong Deng,1,* Jie-Ping Chen,1 Kang-Bo Huang,1,2 Ting-Yu Liu,1,2 Kai Yao,1,2 Zhuo-Wei Liu,1,2 Zi-Ke Qin,1,2 Yong-Hong Li,1,2 Sheng-Jie Guo,1,2 Yun-Lin Ye,1,2 Fang-Jian Zhou,1,2 Wenlin Huang,1,3 Ran-Yi Liu,1 Hui Han1,2 1State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China; 2Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China; 3Guangdong Provincial Key Laboratory of Tumor Targeted Drugs, Guangzhou Enterprise Key Laboratory of Gene Medicine, Guangzhou Doublle Bioproducts Co. Ltd., Guangzhou, China *These authors contributed equally to this work Purpose: Molecular biomarkers, especially serologic factors, have been widely applied in cancer diagnosis and patient follow-up. However, there are few valuable prognostic factors in penile squamous cell carcinoma (PSCC). Here, the authors investigated whether laminin gamma 2 (LAMC2) expression, especially serum LAMC2 (sLAMC2) level, was a suitable prognostic factor that could aid in the prediction of survival in PSCC.Patients and methods: This study included 114 PSCC patients. Reverse transcription-quantitative polymerase chain reaction, Western blotting, and immunohistochemistry were performed to detect LAMC2 expression; enzyme-linked immunosorbent assays were used to test sLAMC2 concentration; and a Transwell assay and an in vivo experiment in nude mice were used to test PSCC cell migration, invasion, and metastasis. The chi-squared test was used to analyze the association between LAMC2 level and clinical parameters, the Cox proportional hazards regression model was used to evaluate the hazard ratio for death, and Kaplan–Meier analysis with a log-rank test was used for the survival analysis.Results: LAMC2 was overexpressed in PSCC tissues, and the LAMC2 expression level was higher in metastatic lymph node (LN) tissues than in primary cancer tissues; moreover, the LAMC2 levels in primary cancer tissues and sLAMC2 were higher in patients with LN metastasis than in those without LN metastasis. Upregulated LAMC2 facilitated the migration, invasion, and epithelial-to-mesenchymal transition of PSCC cells in vitro and promoted LN metastasis of PSCC cells in nude mice. Elevated LAMC2 levels were strongly correlated with advanced clinicopathologic parameters, especially LN metastasis, in PSCC patients and predicted shorter disease-specific survival. The predictive value of sLAMC2 is superior to that of C-reactive protein and squamous cell carcinoma antigen previously reported in PSCC patients, and a stratification analysis revealed that the level of sLAMC2 had a higher predictive value for disease-specific survival in early penile cancer (especially at the N0/X stage) than in later-stage penile cancer.Conclusion: These findings suggest that sLAMC2 is a potential serologic prognostic marker in PSCC and could aid in risk stratification in early-stage PSCC patients. Keywords: penile neoplasms, serum markers, laminin, gamma 2, neoplasm metastasis

// Zai-Shang Li 1, 2, 3, * , Chuang-Zhong Deng 1, 2, 3, * , Yun-Lin Ye 1, 2, 3, * , Kai Yao 1, 2, 3 , Sheng-Jie Guo 1, 2, 3 , Jie-Ping Chen 1, 2, 3 , Yong-Hong Li 1, 2, 3 , Zi-Ke Qin 1, 2, 3 , Zhuo-Wei Liu 1, 2, 3 , Bin Wang 4 , Qi Zhao 1, 2, 5 , Peng Chen 6 , Qi-Wu Mi 7 , Xiao-Feng Chen 8 , Hui Han 1, 2, 3 and Fang-Jian Zhou 1, 2, 3 1 Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China 2 State Key Laboratory of Oncology in Southern China, Guangzhou, P. R. China 3 Collaborative Innovation Center of Cancer Medicine, Guangzhou, P. R. China 4 Department of Urology, Cancer Center of Guangzhou Medical University, Guangzhou, P. R. China 5 School of Life Science, Sun Yat-sen University, Guangzhou, P. R. China 6 Department of Urology, Affiliated Tumor Hospital of Xinjiang Medical University, Urumchi, P. R. China 7 Department of Urology, Dong Guan People’s Hospital, Guang Dong, P. R. China 8 Department of Urology, The First People's Hospital of Chenzhou, Chenzhou, P. R. China * First authors, they contributed equally to this research Correspondence to: Hui Han, email: hanhui@sysucc.org.cn Fang-Jian Zhou, email: zhoufj@sysucc.org.cn Keywords: casein kinase 2α, penile neoplasm, squamous cell carcinoma Received: September 13, 2016 Accepted: February 21, 2017 Published: May 16, 2017 ABSTRACT Purpose: In this study, we assess the CK2α expression in human penile squamous cell carcinoma (SCC) and its clinical significance. Methods: A total of 157 human penile SCC tissue samples were immunohistochemically analyzed. In addition, 12 human penile SCC and adjacent normal tissues were examined for CK2α protein and mRNA expression by Western blotting and real-time quantitative PCR, respectively. Survival was analyzed using the Kaplan-Meier test and the log-rank test. Multivariate Cox proportional hazard regression analysis was performed to determine the impacts of CK2α expression and the clinicopathological features on patient disease-specific survival (DSS). Likelihood ratios (LRs), Akaike information criterion (AIC) values, and concordance indexes (C-indexes) were investigated to evaluate the accuracies of the factors. Bootstrap-corrected C-indexes were used for internal validation (with sampling 1000 times). Results: A significant difference in the distribution of CK2α was observed between the normal and penile carcinoma tissues ( P

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.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.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)].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.

Current guidelines recommend pelvic lymphadenectomy (PLND) for patients with pelvic lymph node metastasis and special state. However, these data and recommendations do not distinguish the role of PLND in different patient groups and confirm the final benefits. The aim of this study was to confirm the efficacy of pelvic lymphadenectomy (PLND) for the different groups of patients. Data obtained from 7 centers were retrospectively analyzed. Of the patients, 190 pN2-3 penile carcinoma patients confirmed by bilateral inguinal lymph node excision were included in this study. Sixty-nine and 121 of these patients did and did not undergo bilateral PLND, respectively. The baseline differences from the patients were matched by propensity score analysis. In this study, the Kaplan–Meier estimated disease-specific survival (DSS) was not significantly different between the PLND and no-PLND groups (P = 0.796). According to the propensity score matching for T stage, N stage, grade, adjuvant therapies, and lymph node stage (number of inguinal lymph node metastasis and extranodal extension), 48 patients were selected for each group. Among the pN2 patients, the PLND group showed higher DSS rates than the no-surgery group (P = 0.030). However, even after matching, survival did not differ between the PLND and no-PLND patients among all patients (P = 0.609) and pN3 patients (P = 0.417) with comparable DSS. Bilateral PLND may improve survival in pN2 patients. Men with pN3 may not benefit from bilateral PLND.

Object: In this study, we evaluated the role of lymph node density (LND) and validated whether LND increases the accuracy of survival prediction when combined with the American Joint Committee on Cancer (AJCC) pathological node (N) staging system for penile cancer (7th edition). Methods: A total of 270 Chinese penile cancer patients treated between March 1999 and October 2014 were retrospectively analyzed. LND was analyzed as a trichotomous variable for the prediction of DSS in this cohort. We developed a new prediction model, which we refer to as the ND staging system, that is based on LND and pathological N staging. The predictive accuracy of this model was further assessed using the concordance index. Results: LND was correlated with the laterality of lymph node metastasis, extranodal extension, pelvic lymph node metastases, and pathologic tumor (T) and N stages (P

To evaluate risk factors of relapse in pediatric patients with clinical stage I (CS1) testicular yolk sac tumors. 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. 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

Background The 8th American Joint Committee on Cancer tumor–node–metastasis (AJCC-TNM) staging system is based on a few retrospective single-center studies. We aimed to test the prognostic validity of the staging system and to determine whether a modified clinicopathological tumor staging system that includes lymphovascular embolization could increase the accuracy of prognostic prediction for patients with stage T2–3 penile cancer. Methods A training cohort of 411 patients who were treated at 2 centers in China and Brazil between 2000 and 2015 were staged according to the 8th AJCC-TNM staging system. The internal validation was analyzed by bootstrap-corrected C-indexes (resampled 1000 times). Data from 436 patients who were treated at 15 centers over four continents were used for external validation. Results A survivorship overlap was observed between T2 and T3 patients (P = 0.587) classified according to the 8th AJCC-TNM staging system. Lymphovascular embolization was a significant prognostic factor for metastasis and survival (all P

Cell line models are essential tools to study the molecular mechanisms underlying tumor initiation and progression. There are limited treatment options for penile squamous cell carcinoma (PSCC), accounting for 1–2% of male tumors in developing countries, and limited progress in preclinical research in PSCC due to lacking available models with identified genomic characteristics. Here, biological and molecular characteristics and whole-genomic alterations were analyzed in a panel of PSCC cell lines newly established in our laboratory. These cell lines were all human papillomavirus (HPV)-negative, epithelial-like, immortalized, and tumorigenic in nude mice, whereas they displayed different proliferation, migration and invasion capacities in vitro, and tumorigenic ability in nude mice. They were all cisplatin sensitive, anti-EGFR therapy resistant, and androgen irresponsive. Whole-genomic sequecing analysis revealed that transition mutations (C:G>T:A and T:A>C:G) were the most common substitution types in these cell lines, whereas ERCC5, TP53, PTH1, CLTCL1, NOTCH2, MAP2K3, CDK11A/B, USP6, ADCH5, BCLAF1, CDKN2A, FANCD2, HRAS, and NOTCH1 were the most frequently altered genes. Amplifications of MYC, PLAG1, NCOA2, RUNX1T1, COX6C, and EGFR and losses of FBXW7, TET2, XPC, and FANCE were frequently observed in cell lines. The exomic variations between cell lines and their corresponding cancer tissues were highly consistent. Genetic variations were mainly involved in the MAPK, Jak-STAT, TGF-beta, Notch, and apoptosis signaling pathways. Conclusively, these panel of PSCC cell lines established in our laboratory harbor some common or specific biological characteristics and genomic variations, and they may serve as optimal models to investigate the molecular mechanisms underlying the progression, metastasis, relapses, and treatment resistance of PSCC and to develop effective treatment strategy.

Clinically, most of human urothelial carcinoma of the bladder (UCB)-related deaths result from tumor metastasis, but the underlying molecular mechanisms are largely unknown. Recently, a growing number of tripartite motif (TRIM) family members have been suggested to be important regulators for tumorigenesis. However, the impact of most TRIM members on UCB pathogenesis is unclear. In this study, TRIM65 was first screened as an important oncogenic factor of UCB from the Cancer Genome Atlas (TCGA) database and was validated by a large cohort of clinical UCB tissues. By in vitro and in vivo experiments, we demonstrated that TRIM65 promotes UCB cell invasive and metastatic capacities. Notably, we showed that TRIM65 modulates cytoskeleton rearrangement and induces UCB cells epithelial-mesenchymal transition by the ubiquitination of ANXA2, ultimately leading to an enhanced invasiveness of UCB cells. Importantly, UCBs with high expression of TRIM65 and low expression of ANXA2 showed the poorest outcome. Collectively, our results suggest that the overexpression of TRIM65 has an essential oncogenic role via ubiquitination of ANXA2 in UCB pathogenesis, and that such could be used as a novel prognostic marker and/or therapeutic target for UCB.

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.

Objective To investigate the value of removed lymph node (LN) count and LN density (LND) for predicting disease-specific survival (DSS) rate following radical lymphadenectomy in patients with penile cancer. Methods We retrieved data from 146 patients who were surgically treated between 2002 and 2012. receiver-operating characteristic curve analysis was used to calculate the optimal cutoff value of LN count and LND for predicting DSS rate. LND was analyzed as a categorical variable by grouping patients with pN+tumors into 2 categories. Multivariate Cox regression analysis was used to test the effect of various variables on DSS rate based on collinearity in various models. Results Median follow-up was 42 months. Overall, 75 patients (51.4%) had pN0 disease, and 71 patients (48.6%) had pN+disease. The optimal cutoff value of LN count and LND were 16% and 16%, respectively. Among patients with pN0 tumors, the number of LNs removed (≥16 LNs) was an independent significant predictor of DSS rate in univariate and multivariate analyses (all P P Conclusions The removal of at least 16 LNs was associated with a significantly longer DSS rate in patients with pN0 penile cancer. Additionally, an LND above 16% is an independent predictor of DSS rate in patients with pN+tumors. Further independent validation is required to determine the clinical usefulness of LN count and LND in this patient population.

The prognosis of locally advanced or recurrent squamous cell carcinoma (SCC) of the penis after conventional treatment is dismal. This study aimed to evaluate the therapeutic effects of intraarterial chemotherapy with gemcitabine and cisplatin on locally advanced or recurrent SCC of the penis. Between April 1999 and May 2011, we treated 5 patients with locally advanced penile SCC and 7 patients with recurrent disease with intraarterial chemotherapy. The response rate and toxicity data were analyzed, and survival rates were calculated. After 2 to 6 cycles of intraarterial chemotherapy with gemcitabine and cisplatin, 1 patients with locoregionally advanced disease achieved a complete response, and 4 achieved partial response. Of the 7 patients with recurrent disease, 2 achieved complete response, 3 achieved partial response, 3 had stable disease, and 1 developed progressive disease. An objective tumor response was therefore achieved in 10 of the 12 patients. The median overall survival for the patients was 24 months (range, 10-50 months). Three out of 10 patients who responded were long-term survivors after intraarterial chemotherapy. Intraarterial chemotherapy with gemcitabine and cisplatin may be effective and potentially curative in locoregionally advanced or recurrent penile SCC. The contribution of this therapy in the primary management of advanced or recurrent penile SCC should be prospectively investigated.

Objective To investigate local groin recurrence and morbidity associated with fascia lata preservation during inguinal lymphadenectomy (LAD) for penile carcinoma. Methods Between January 2002 and December 2011, 201 inguinal dissections with preservation of the fascia lata were performed in 104 patients with clinical disease staged at ≤N2. The dissection boundaries were the same as those for radical inguinal LAD. All superficial inguinal nodes were removed en bloc. The cribriform fascia near the femoral canal was divided, and the deep inguinal lymph nodes were dissected. The fascia lata was completely preserved and sutured to the subcutaneous tissue. Sartorius muscle transposition was eliminated. Survival and morbidity data were retrospectively analyzed, and survival probabilities were calculated. Results The median operative time for unilateral inguinal LAD was 45 minutes (range, 40-60 minutes). Median follow-up was 36 months (range, 10-130 months). A mean number of 12.5 nodes were removed per groin. One patient (1%) had a recurrence outside the borders of the fascia lata after 7 months of follow-up. The 3-year disease-free survival rate was 92.1% (100% for pN0, 91.3% for pN1, 80% for pN2, and 33.3% for pN3 disease). A total of 59 complications (29.3%) occurred, including wound infection (2.5%), skin necrosis (5.5%), lymphedema (11.8%), seroma formation (1.5%), lymphocele (5%), paresthesia (3.5%), and deep venous thrombosis (0.5%). Conclusion Inguinal dissections with preservation of the fascia lata for penile carcinoma patients without extranodal extension is as effective as the classic dissection technique but decreases complications related to groin dissection.

The reporting of complications following transperitoneal and retroperitoneal open radical nephrectomy (RN) is nonstandardized. This study aimed to compare early complications between the two approaches using a standardized reporting methodology in a large contemporary cohort. Between 1996 and 2009, 558 patients underwent open RN for renal cell carcinoma (RCC) in our two centers (424 from Sun Yat-sen University Cancer Center and 134 from the First Affiliated Hospital of Sun Yat-sen University). Records were reviewed for clinicopathologic features and complications. Complications were graded using the Clavien system based on the severity of impact. One hundred and five patients (18.8%) had one or more early complications (168 complications overall). The overall rates of grades I to V complications were 5.6%, 10.8%, 2.2%, 0.4%, and 0.2%, respectively. Patients who underwent transperitoneal RN did not experience more overall or procedure-related complications than those who underwent retroperitoneal RN (P = 0.911 and P = 0.851, respectively). On subgroup analysis, neither grade I/II nor grades III-V complications were significantly different between the transperitonal RN and retroperitoneal RN groups. Multivariate analysis showed that for any grade of complication, age (P = 0.016) and estimated blood loss (P = 0.001) were significant predictors. We concluded that open RN is a safe procedure associated with low rates of serious morbidity and mortality. Compared with retroperitoneal RN, transperitoneal RN was not associated with more complications. Older patient and more blood loss at surgery were independent predictors for higher early postoperative complication rates.

This study assesses the long-term outcomes in Han Chinese patients with clinical stage I non-seminomatous germ cell testicular cancer (CSI NSGCT) treated with surveillance, retroperitoneal lymph node dissection (RPLND) and adjuvant chemotherapy. We retrospectively evaluated 89 patients with a mean age of 26.5 years. After orchiectomy, 37 patients were treated with surveillance, 34 underwent RPLND and 18 were managed with chemotherapy. The overall survival rate, the recurrence-free survival rate and the risk factors were evaluated. The median follow-up length was 92 months (range: 6–149 months). Thirteen of the 89 patients (14.6%) had relapses, and one died by the evaluation date. The overall survival rate was 98.9%. The cumulative 4-year recurrence-free rates were 80.2%, 92.0% and 100% for the surveillance, RPLND and chemotherapy groups, respectively. The disease-free period tended to be briefer in patients with a history of cryptorchidism and those with stage Is. Therefore, surveillance, RPLND and adjuvant chemotherapy might be reliable strategies in compliant patients with CSI NSGCT. Surveillance should be recommended for patients with the lowest recurrence rate, especially those without lymphovascular invasion. This study might aid the establishment of a standard therapy for CSI NSGCT in China.

During partial nephrectomy (PN), artery-only (AO) occlusion may mitigate ischemia/reperfusion injury because of retrograde venous flow. Using digital light processing-hyperspectral imaging (DLP(®)-HSI), we compared renal oxygenation during AO vs artery and vein (AV) occlusion in patients undergoing PN.Thirty-seven patients who were undergoing complex open PN (median R.E.N.A.L. nephrometry of 8) at our institution underwent renal oxygenation assessment using DLP-HSI. Percent renal parenchymal oxyhemoglobin (%HbO2) during AO vs AV occlusion was recorded and its correlation with postoperative estimated glomerular filtration rate (eGFR) was investigated using Pearson correlation. AO and AV occlusion was performed in 12 and 25 patients, respectively.Comparing AO vs AV, mean ischemia time was 41 vs 35 minutes (P=0.02). The %HbO2 at baseline was 73.6% vs 71% (P=0.23). After hilar occlusion, %HbO2 quickly reached an "ischemic plateau" in both groups, with mean ischemic %HbO2 measures of 59.7% vs 62.2% (P=0.19). In the AV group, a lower mean ischemic %HbO2 was associated with lower eGFR at the most recent follow-up (r=0.46, P=0.02) and remained significant on multivariable analysis (odds ratio 2.31; 95% confidence interval 0.29-4.32; P=0.03).In this pilot clinical study, renal oxygenation profiles during PN as assessed by DLP-HSI were similar for AO vs AV occlusion. Significant retrograde venous oxygen delivery using an AO occlusion technique could not be demonstrated. There was also no renal functional advantage for AO occlusion in this population of difficult PN where prolonged ischemia times may have mitigated any advantage. Further study in cases with shorter ischemia times is warranted.

To compare surgeon-assessed ergonomic and workload demands of magnetic anchoring and guidance system (MAGS) laparoendoscopic single-site surgery (LESS) nephrectomy with conventional LESS nephrectomy in a porcine model.Participants included two expert and five novice surgeons who each performed bilateral LESS nephrectomy in two nonsurvival animals using either the MAGS camera or conventional laparoscope. Task difficulty and workload demands of the surgeon and camera driver were assessed using the validated National Aeronautics and Space Administration Task Load Index (NASA-TLX) questionnaire. Surgeons were also asked to score 6 parameters on a Likert scale (range 1=low/easy to 5=high/hard): procedure-associated workload, ergonomics, technical challenge, visualization, accidental events, and instrument handling. Each step of the nephrectomy was also timed and instrument clashing was quantified.Scores for each parameter on the Likert scale were significantly lower for MAGS-LESS nephrectomy. Mean number of internal and external clashes were significantly lower for the MAGS camera (p0.001). Mean task times for each procedure were shorter for experts than for novices, but this was not statistically significant. NASA-TLX workload ratings by the surgeon and camera driver showed that MAGS resulted in a significantly lower workload than the conventional laparoscope during LESS nephrectomy (p0.05).The use of the MAGS camera during LESS nephrectomy lowers the task workload for both the surgeon and camera driver when compared to conventional laparoscope use. Subjectively, it appears to also improve surgeons' impressions of ergonomics and technical challenge. Pending approval for clinical use, further evaluation in the clinical setting is warranted.

To compare the ergonomics and workload of the surgeon during single-site suturing while using the magnetic anchoring and guidance system (MAGS) camera vs a conventional laparoscope.Seven urologic surgeons were enrolled and divided into an expert group (n=2) and a novice group (n=5) according to their laparoendoscopic single-site (LESS) experience. Each surgeon performed 2 conventional LESS and 2 MAGS camera-assisted LESS vesicostomy closures in a porcine model. A Likert scale (scoring 1-5) questionnaire assessing workload, ergonomics, technical difficulty, visualization, and needle handling, as well as a validated National Aeronautics and Space Administration Task Load Index (NASA-TLX) questionnaire were used to evaluate the tasks and workloads.MAGS LESS suturing was universally favored by expert and novice surgeons compared with conventional LESS in workload (3.4 vs 4.2), ergonomics (3.4 vs 4.4), technical challenge (3.3 vs 4.3), visualization (2.4 vs 3.3), and needle handling (3.1 vs 3.9 respectively; P.05 for all categories). Surgeon NASA-TLX assessments found MAGS LESS suturing significantly decreased the workload in physical demand (P=.004), temporal demand (P=.017), and effort (P=.006). External instrument clashing was significantly reduced in MAGS LESS suturing (P.001). The total operative time of MAGS LESS suturing was comparable to that of conventional LESS (P=.89).MAGS camera technology significantly decreased surgeon workload and improved ergonomics. Nevertheless, LESS suturing and knot tying remains a challenging task that requires training, regardless of which camera is used.

To evaluate the efficacy of periprostatic nerve block anesthesia (PPNB) for pain relief in transrectal ultrasound-guided systematic prostate biopsy (PBx).We reviewed the data of patients undergoing initial PBx at our center from November, 2013 to January, 2015. Only the patients with 12-core systemic PBx were included and 111 patients were eligible for this study, among whom 52 patients received PPNB and 59 did not. PPNB was achieved by an injection of 5 mL of 1% lidocaine at the angle between the seminal vesicle and base of the prostate on each side before biopsy. The DRE pain score, probe insert pain score, and biopsy pain score were assessed by visual analogue scale (VAS) immediately after the biopsy. The complications were recorded and evaluated immediately after and at 7 days after the biopsy.The mean age, prostate volume, total prostate specific antigen (tPSA), free PSA (fPSA), and abnormal DRE were comparable between the 2 groups (P0.05). Immediately after the biopsy, no difference was found between the 2 groups in DRE pain score (1.40±0.98 vs 1.39±0.91, P=0.102) or probe insert pain score (2.07±0.96 vs 2.03±0.90, P=0.960), but the biopsy pain score was significantly lower in PPNB group than in no PPNB group (2.54±1.42 vs 3.07±1.43, P=0.033). The incidence of the procedure-related complications was similar between the 2 groups (P0.05).PPNB can significantly lower the biopsy pain score in PBx without increasing the incidence of complications.

RNF2 (ring finger protein 2) is frequently overexpressed in several types of human cancer, but the status of RNF2 amplification and expression in urothelial carcinoma of the bladder (UCB) and its clinical/prognostic significance is unclear. In this study, immunohistochemical analysis and fluorescence in situ hybridization (FISH) were used to examine the expression and amplification of RNF2 in 184 UCB patients after radical cystectomy. Overexpression of RNF2 was observed in 44.0% of UCBs and was found to significantly associate with shortened overall and cancer-specific survival (P P P RNF2 in 8/79 (10.1%) of informative UCB cases. Additionally, RNF2 overexpression was significantly associated with RNF2 gene amplification (P = 0.004) and cell proliferation (P = 0.003). These findings suggested that overexpression of RNF2, as examined by immunohistochemical analysis, might serve as a novel prognostic biomarker and potential therapeutic target for UCB patients who undergo radical cystectomy.

The study aims to investigate the changes and regulation of androgen receptor and insulin-like growth factor-1 in the PC3 prostate cells treated with 5α-dihydrotestosterone, estrone, and flutamide. The PC3 cells were cultured and treated with 5α-dihydrotestosterone, estrone, and flutamide. Immunocytochemistry and Western blot were used to detect the expression of androgen receptor and insulin-like growth factor-1. The androgen receptor expression was analyzed by Western blot and optic density scan in the presence or absence of various kinase inhibitors. The statistical calculations were performed with the statistics-analyzing software package SPSS 13.0. A P

The prognostic features of T1N0M0 renal cell carcinoma (RCC) in Asian patients have not been well explored in large sample studies. In this study, we retrospectively analyzed the records of 713 patients undergoing nephrectomy for T1N0M0 RCC between 1991 and 2009 in three Asian hospitals. Univariate and multivariate analysis were performed to identify the independent predictive factors for T1N0M0 RCC prognosis among a series of Clinicopathological parameters, including age, gender, tumor size, Fuhrman grade, and histological classification. Our results showed that 388 of 713 patients had tumors 4.0 cm or smaller (stage T1a) and 325 of 713 patients had tumors 4.0–7.0 cm in size (stage T1b). Five-year cancer-specific survival (CSS) and recurrence-free survival (RFS) rates for this group of patients were 96.0% and 93.5%, respectively. The patients with T1b RCC had a significantly lower 5-year CSS and RFS rates than did those with T1a RCC (CSS, 93.1% vs. 98.6%, P = 0.026; RFS, 90.0% vs. 96.5%, P < 0.001). Patients with low grade (grades I–II) tumors had a higher 5-year CSS (97.8% vs. 91.2%, P = 0.001) and RFS (95.5% vs. 85.5%, P < 0.001) rate than did those with high grade (grades I–II) tumors. More interestingly, when stratifying patients to T1a and T1b groups, the role of grade in distinguishing prognosis could be only observed in patients with T1b disease. Cox regression showed tumor size and Fuhrman grade were significant in predicting CSS and RFS. Our study suggests that the prognosis of patients with T1N0M0 RCC is excellent, and these results are comparable to previously reported studies in Western patients. Furthermore, our data indicates that patients with T1b disease and high Fuhrman grade have high risk of tumor recurrence and death, thus requiring more frequent follow-up.

The aim of the present study was to assess the treatment outcomes in a cohort of adult patients with intratesticular rhabdomyosarcoma. Between 1999 and 2008, 296 patients underwent radical orchiectomy for intrascrotal mass. A retrospective chart review was carried out for adult patients diagnosed with intratesticular rhabdomyosarcoma. Overall, six patients (mean age 21 years, range 17-23) were included: five had embryonic rhabdomyosarcoma and one had pleomorphic rhabdomyosarcoma. Four patients underwent retroperitoneal lymph node dissection and five patients had postoperative chemotherapy. The mean length of follow up was 28 months (range 12-51 months). One patient was lost to follow up after 26 months, five cases remained alive at the end of the study. Surgical resection with chemotherapy was an effective way to achieve favorable outcomes and long-term survival in adult patients with metastases from intratesticular rhabdomyosarcoma.

Objective: To analyze the incidence of benign lesions in Chinese patients undergoing nephrectomies for renal masses identified as localized renal cell carcinoma (RCC) in preoperative imaging. Methods: Between 1999 and 2007, 303 patients (112 female, 191 male) with presumed localized RCC underwent nephrectomy (234 radical nephrectomies and 69 partial nephrectomies). Preoperative computed tomography images and pathological findings were reviewed and analyzed. Results: Pathological examinations revealed 31 (10.2%) benign lesions in the 303 patients. Among these 31 benign lesions, 15 (5.0%) were angiomyolipomas (AML) and only four (1.3%) were oncocytomas. Significantly, 20 (17.9%) of the 112 female patients had benign lesions compared with 11 (5.8%; P = 0.001) male patients. Benign renal lesions were found in five (25.0%) of the 20 patients with renal masses smaller than 2 cm, 13 (13.0%) of the 100 patients with renal masses 2–4 cm in size and 13 (7.1%) of the 183 patients with renal masses larger than 4 cm. Conclusions: Patients in the present study population show a low incidence of benign renal lesions, approximately half of them being AML. Female patients and patients with renal masses smaller than 4 cm are more likely to have benign renal lesions.

To introduce a modified technique for urethral anastomosis in orthotopic neobladder reconstruction.Between January 2002 and August 2008, about 141 consecutive patients (130 men and 11 women) underwent total cystectomy and orthotopic neobladder reconstruction in which a modified technique was used to anastomosed the caudal-most part of the intestinal neobladder directly to the urethral remnant. The emptying of the neobladder, the early and late complications at the urethral anastomosis was evaluated.Mean patient age at surgery was 58.4 years (range, 33-83) and median follow-up was 42 months (range, 4-83 months). Early urine leakage at the vesicourethral anastomosis developed in 1 patient, and was cured by extending catheter drainage. A total of 138 patients had good emptying of the neobladder, with residual urine volume50 mL. Three patients had residual urine volume100 mL, and achieved good emptying after intermittent catheterization once a week for 6-12 months. No late complications occurred at the urethral anastomosis site. Daytime continence was good or satisfactory in 97.0% of patients and night-time continence was good or satisfactory in 88.5% of patients.The clinical outcome of our modified technique for urethral anastomosis in orthotopic neobladder substitution was excellent, but the advantage of this technique needs prospective controlled study.

Objective We reviewed our experience with dilation of the upper urinary tract caused by the conglutination of distal ureters after orthotopic neobladder reconstruction using the split-cuff nipple ureteral reimplant technique. Materials and methods From January 2000 to April 2007, 250 consecutive patients underwent radical cystectomy and orthotopic neobladder reconstruction. Ureterointestinal anastomosis was performed using the split-cuff nipple technique in 291 renoureteral units. The patients from a single center were followed up for a mean period of 8 months (range 1–22) after surgery. We incised the conglutination band using a transurethral endoscope. Patient characteristics, endoscopic technique, measurement of serum creatinine levels, and results of ultrasonography, cystoscopy, and excretory urography were collected. Results Hydronephrosis was found in 8 patients (14 renoureteral units) due to the conglutination of the distal ureters to each other (n = 6) or to the neobladder wall (n = 2). After the incision procedure, seven patients had obvious improvement in renal function and hydronephrosis, and their symptoms disappeared. In 1 patient, hydronephrosis developed again because of ureteroenteric stenosis after 7 months and was resolved by open surgical revision. The hydronephrosis had improved greatly in this patient by 5 months after revision. Conclusion Conglutination of the distal ureters is a cause of hydronephrosis after orthotopic neobladder reconstruction using the reimplant technique with the split-cuff nipple. Cystoscopy is mandatory in following up patients who have hydronephrosis with the split-cuff nipple ureteral reimplant technique, not only to confirm the diagnosis but to treat the complication by incising the conglutination band. Continued follow-up is required to evaluate the long-term results of this treatment.

// Zhi Yong Li 1, 2, 3, * , Xin Xiang Fan 4, * , Yan Jun Wang 1, 2, 3, * , Kai Yao 1, 2, 3 , Zhuo Wei Liu 1, 2, 3 , Wen Tao Pan 1, 2, 3 , Yun Lin Ye 1, 2, 3 , Ping Yang 1, 2, 3 , Yi Chuan Huang 4 , Zhi Ming Wu 1, 2, 3 , Fang Jian Zhou 1, 2, 3 1 State Key Laboratory of Oncology in Southern China, Guangzhou, China 2 Department of Urology, Sun Yat-Sen University Cancer Center, Guangzhou, China 3 Collaborative Innovation Center for Cancer Medicine, Guangzhou, China 4 Department of Urology, Sun Yat-Sen Memorial Hospital, Guangzhou, China * These authors contributed equally to this work Correspondence to: Zhi Ming Wu, email: wuzhim@sysucc.org.cn Fang Jian Zhou, email: zhoufj@sysucc.org.cn Keywords: RCC, sorafenib, TKIs, CRVO, unilateral Received: December 07, 2015 Accepted: March 28, 2016 Published: May 11, 2016 ABSTRACT Background: Renal cell carcinoma (RCC) is the most common type of kidney tumor with increasing incidence. Tyrosine Kinase Inhibitors (TKIs) are considered important treatment in the management of metastatic RCC. Some previous studies demonstrated that sorafenib treatment is associated with a significantly increased risk of potentially life-threatening adverse events, like bleeding. But bleeding at the fundus site is the rarest type of hemorrhage. As for TKIs’ risk of bleeding, how we distinguish the degree of bleeding and what optimal strategies should we take to manage bleeding, needs to be studied systematically. Results: With a long-term exposure (17 months) to sorafenib, he experienced blurred vision in his right eye and was hospitalized. The patient’s diagnosis was central retinal vein occlusion (CRVO) of the right eye. Unfortunately sorafenib was terminated. Materials and Methods: The authors describe the first case of unilateral fundus hemorrhage induced by sorafenib. A 42-year-old man was diagnosed metastatic left RCC, with clinical stage and prognostic risk being assessed as T4N1M1 and intermediate. He received a radical left nephrectomy and retroperitoneal lymph node dissection, with taking the oral multi-targeted TKI, sorafenib (800 mg daily) from 7 months to 7 days before the surgery and 7 days after the surgery restarting again until the occurrence of fundus hemorrhage. Conclusions: In this patient, long-term exposure to sorafenib possibly has increased the risk of fundus hemorrhage. This article provides us a previously undescribed morbidity associated with sorafenib, which reminds us of understanding the risk of bleeding and how this complication might be managed systematically.

// Zai-Shang Li 1,2,3,* , Peng Chen 4,* , Kai Yao 1,2,3,* , Bin Wang 5,* , Jing Li 5 , Qi-Wu Mi 6 , Xiao-Feng Chen 7 , Qi Zhao 8 , Yong-Hong Li 1,2,3 , Jie-Ping Chen 1,2,3 , Chuang-Zhong Deng 1,2,3 , Yun-Lin Ye 1,2,3 , Ming-Zhu Zhong 9 , Zhuo-Wei Liu 1,2,3 , Zi-Ke Qin 1,2,3 , Xiang-Tian Lin 10 , Wei-Cong Liang 10 , Hui Han 1,2,3 and Fang-Jian Zhou 1,2,3 1 Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China 2 State Key Laboratory of Oncology in Southern China, Guangzhou, P. R. China 3 Collaborative Innovation Center of Cancer Medicine, Guangzhou, P. R. China 4 Department of Urology, Affiliated Tumor Hospital of Xinjiang Medical University, Urumchi, P. R. China 5 Department of Urology, Cancer Center of Guangzhou Medical University, Guangzhou, P. R. China 6 Department of Urology, Dong Guan People’s Hospital, Guang Dong, P. R. China 7 Department of Urology,The First People’s Hospital of Chenzhou, Chenzhou, P. R. China 8 School of Life Science, Sun Yat-sen University, School of Life Science, Guang Dong, P. R. China 9 Department of Urology, The People’s Hospital of Jiangmen, Jiangmen, P. R. China 10 Zhongshan School of Medicine, Sun Yat-sen University, Guang Dong, P. R. China * These authors have contributed equally to this work Correspondence to: Hui Han, email: // Fang-Jian Zhou, email: // Keywords : penile neoplasms, neoplasm staging, prognosis, body mass index, C-reactive protein Received : October 25, 2015 Accepted : January 24, 2016 Published : March 11, 2016 Abstract Purpose: To determine the predictive value and feasibility of the new outcome prediction model for Chinese patients with penile squamous cell carcinoma. Results: The 3-year disease-specific survival (DSS) was 92.3% in patients with < 8.70 mg/L CRP and 54.9% in those with elevated CRP ( P < 0.001). The 3-year DSS was 86.5% in patients with a BMI < 22.6 Kg/m2 and 69.9% in those with a higher BMI ( P = 0.025). In a multivariate analysis, pathological T stage ( P < 0.001), pathological N stage ( P = 0.002), BMI ( P = 0.002), and CRP ( P = 0.004) were independent predictors of DSS. A new scoring model was developed, consisting of BMI, CRP, and tumor T and N classification. In our study, we found that the addition of the above-mentioned parameters significantly increased the predictive accuracy of the system of the American Joint Committee on Cancer (AJCC) anatomic stage group. The accuracy of the new prediction category was verified. Methods: A total of 172 Chinese patients with penile squamous cell cancer were analyzed retrospectively between November 2005 and November 2014. Statistical data analysis was conducted using the nonparametric method. Survival analysis was performed with the log-rank test and the Cox proportional hazard model. Based on regression estimates of significant parameters in multivariate analysis, a new BMI-, CRP- and pathologic factors-based scoring model was developed to predict disease-specific outcomes. The predictive accuracy of the model was evaluated using the internal and external validation. Conclusion: The present study demonstrated that the TNCB score group system maybe a precise and easy to use tool for predicting outcomes in Chinese penile squamous cell carcinoma patients.

We have recently identified and characterized a novel oncogene, maelstrom (MAEL) from 1q24, in the pathogenesis of hepatocellular carcinoma. In this study, MAEL was investigated for its oncogenic role in urothelial carcinoma of the bladder (UCB) tumorigenesis/aggressiveness and underlying molecular mechanisms. Here, we report that overexpression of MAEL in UCB is important in the acquisition of an aggressive and/or poor prognostic phenotype. In UCB cell lines, knockdown of MAEL by short hairpin RNA is sufficient to inhibit cell growth, invasiveness/metastasis and suppressed epithelial-mesenchymal transition (EMT), whereas ectopic overexpression of MAEL promoted cell growth, invasive and/or metastatic capacity and enhanced EMT both in vitro and in vivo. We further demonstrate that MAEL could induce UCB cell EMT by downregulating a critical downstream target, the metastasis suppressor 1 (MTSS1) gene, ultimately leading to an increased invasiveness of cancer cells. Notably, overexpression of MAEL in UCB cells substantially enhanced the enrichment of DNA methyltrans-ferase (DNMT)3B and histone deacetylase (HDAC)1/2 on the promoter of the MTSS1, and thereby epigenetically suppressing the MTSS1 transcription. Downregulation of MTSS1 by MAEL in UCB cells is partially dependent on DNMT3B. Furthermore, we identify that beside the gene amplification of MAEL, miR-186 is a key negative regulator of MAEL and downregulation of miR-186 is another important mechanism for MAEL overexpression in UCBs. These data suggest that overexpression of MAEL, caused by gene amplification and/or decreased miR-186, has a critical oncogenic role in UCB pathogenesis by downregulation of MTSS1, and MAEL could be used as a novel prognostic marker and/or effective therapeutic target for human UCB.

Numerous experimental therapies to promote axonal regeneration have shown promise in animal models of acute spinal cord injury, but their effectiveness is often found to diminish with a delay in administration. We evaluated whether brain-derived neurotrophic factor (BDNF) application to the spinal cord injury site 2 months after cervical axotomy could promote a regenerative response in chronically axotomized rubrospinal neurons. BDNF was applied to the spinal cord in three different concentrations 2 months after cervical axotomy of the rubrospinal tract. The red nucleus was examined for reversal of neuronal atrophy, GAP43 and Talpha1 tubulin mRNA expression, and trkB receptor immunoreactivity. A peripheral nerve transplant paradigm was used to measure axonal regeneration into peripheral nerve transplants. Rubrospinal axons were anterogradely traced and trkB receptor immunohistochemistry performed on the injured spinal cord. We found that BDNF treatment did not reverse rubrospinal neuronal atrophy, nor promote GAP-43 and Talpha1 tubulin mRNA expression, nor promote axonal regeneration into peripheral nerve transplants. TrkB receptor immunohistochemistry demonstrated immunoreactivity on the neuronal cell bodies, but not on anterogradely labeled rubrospinal axons at the injury site. These findings suggest that the poor response of rubrospinal neurons to BDNF applied to the spinal cord injury site 2 months after cervical axotomy is not related to the dose of BDNF administered, but rather to the loss of trkB receptors on the injured axons over time. Such obstacles to axonal regeneration will be important to identify in the development of therapeutic strategies for chronically injured individuals.