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Bladder cancer is the 10th most prevalent cancer worldwide, with men having a lifetime risk of 1.1% and women 27%. The molecular mechanisms underlying the progression of bladder cancer from non-muscle invasive to muscle invasive are not well understood. This study used high-throughput RNA sequencing to identify differential gene expressions between the two types of bladder cancer. The researchers found that the upregulation of the PHB gene in muscle invasive bladder cancer tissues was associated with increased binding of the NADSYN1 mRNA to the PHB protein. Further experiments demonstrated that the interaction between PHB and NADSYN1 promoted bladder cancer progression. The study also identified Snai2 as a transcription factor that regulates the expression of NADSYN1, and its inhibition was associated with improved survival in bladder cancer patients. [Extracted from the article]

Objective: There is no consensus regarding the best interval time between transurethral resection of a bladder tumor and Bacillus Calmette‐Guerin (BCG) perfusion. This study was to explore whether the interval time has an impact on the prognosis and adverse effects. Methods: We retrospectively reviewed the clinical data of patients who received BCG intravesical perfusion at Sun Yat‐sen University Cancer Center (SYSUCC) from September 2015 to October 2021. Recurrence‐free survival (RFS) and progression‐free survival were the primary endpoints. Cox regression was used to explore independent predictors. The association between interval time and adverse effect grade was detected by logistic regression. Propensity score matching (PSM) was performed. Results: A total of 403 patients were enrolled, the median interval time was 24 days (6–163 days), and the follow‐up was 28 months (7–82 months). Eighty‐eight (20.9%) patients relapsed, and 40 patients (10.0%) suffered progression. The multivariate Cox regression analysis confirmed that interval time was an independent predictor of RFS (p = 0.017). Notably, when the interval time was less than or equal to 26 days, there was a trend toward better RFS, PSM resulted in 65 matched pairs in each group, and Kaplan–Meier analysis showed that there was a significant difference in RFS between groups (p = 0.009). The logistic regression analysis showed that there was no correlation between interval time and adverse effects and their grades (p > 0.05). Conclusions: We considered that the first BCG perfusion could be performed within 2–4 weeks after surgery. [ABSTRACT FROM AUTHOR]

Background: 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.Methods: 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.Results: 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, I2 = 37%). Overall, no significant difference was found in CSS (HR = 0.72, 95% CI: 0.51-1.03, I2 = 0%) and OS (HR = 0.73, 95% CI: 0.45-1.19, I2 = 0%) between patients who underwent diagnostic URS and those who did not. Meanwhile, there was lack of evidence indicating that the risk of tumor metastasis increased after diagnostic URS (HR = 0.97, 95% CI: 0.74-1.26, I2 = 0%).Conclusions: Diagnostic 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background and Purpose: 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. Patients and Methods: 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. Results: 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). Conclusions: 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. [ABSTRACT FROM AUTHOR]

Purpose: 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. Methods: 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. Results: 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 ( p<0.001). 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 ( p<0.05). Conclusions: 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]