Wei Shen Tan

Efficacy and safety of long-acting intramuscular testosterone undecanoate in aging men: a randomised controlled study

To evaluate the efficacy and safety of long‐acting i.m. testosterone undecanoate (TU) in Malaysian men with testosterone deficiency (TD).

Management of non-muscle invasive bladder cancer: A comprehensive analysis of guidelines from the United States, Europe and Asia

Bladder cancer is the 8th most common cancer with 74,000 new cases in the United States in 2015. Non-muscle invasive bladder cancer (NMIBC) accounts for 75% of all bladder cancer cases. Transurethral resection and intravesical treatments remain the main treatment modality. Up to 31-78% of cases recur, hence the need for intensive treatment and surveillance protocols which makes bladder cancer one of the most expensive cancers to manage. The purpose of this review is to compare contemporary guidelines from Europe, (European Association of Urology), the United States (National Comprehensive Cancer Network), the United Kingdom (National Institute for Health and Care Excellence), Japan (Japanese Urological Association) and the International Consultation on Bladder Cancer (ICUD). We compare and contrast the different guidelines and the evidence on which their recommendations are based.

Robot-assisted intracorporeal pyramid neobladder

To describe a robot‐assisted intracorporeal pyramid neobladder reconstruction technique and report operative and perioperative metrics, postoperative upper tract imaging, neobladder functional outcomes, and oncological outcomes.

Epigenetics Markers of Metastasis and HPV-Induced Tumorigenesis in Penile Cancer

Purpose: Penile cancer is a rare malignancy in the developed world with just more than 1,600 new cases diagnosed in the United States per year; however, the incidence is much higher in developing countries. Although HPV is known to contribute to tumorigenesis, little is known about the genetic or epigenetic alterations defining penile cancer. Experimental Design: Using high-density genome-wide methylation arrays, we have identified epigenetic alterations associated with penile cancer. Q-MSP was used to validate lymph node metastasis markers in 50 cases. A total of 446 head and neck squamous cell carcinoma (HNSCC) and cervical squamous cell carcinoma (CESCC) samples were used to validate HPV-associated epigenetic alterations. Results: We defined 6,933 methylation variable positions (MVP) between normal and tumor tissue, which includes 997 hypermethylated differentially methylated regions associated with tumor supressor genes, including CDO1, AR1, and WT1. Analysis of penile cancer tumors identified a 4 gene epi-signature which accurately predicted lymph node metastasis in an independent cohort (AUC of 89%). Finally, we explored the epigenetic alterations associated with penile cancer HPV infection and defined a 30 loci lineage-independent HPV specific epi-signature which predicts HPV status and survival in independent HNSCC, CESC cohorts. Epi-signature–negative patients have a significantly worse overall survival [HNSCC P = 0.00073; 95% confidence interval (CI), 0.021–0.78; CESC P = 0.0094; HR = 3.91, 95% CI = 0.13–0.78], HPV epi-signature is a better predictor of survival than HPV status alone. Conclusions: These data demonstrate for the first time genome-wide epigenetic events involved in an aggressive penile cancer phenotype and define the epigenetic alterations common across multiple HPV-driven malignancies. Clin Cancer Res; 21(5); 1196–206. ©2014 AACR.

The triad of erectile dysfunction, testosterone deficiency syndrome and metabolic syndrome: findings from a multi-ethnic Asian men study (The Subang Men’s Health Study)

The etiology of erectile dysfunction (ED) is multi-factorial. This paper examines the association between ED, testosterone deficiency syndrome (TDS) and metabolic syndrome (MS) in Malaysian men in an urban setting. One thousand and forty-six men aged ≥40 years from Subang Jaya, Malaysia were randomly selected from an electoral-roll list. The men completed questionnaires that included: socio-demographic data, self-reported medical problems and the International Index of erectile function (IIEF-5). Physical examination and the following biochemical tests were performed: lipid profile, fasting blood glucose (FBG) and total testosterone. The response rate was 62.8% and the mean age of men was 55.8 ± 8.4 (41–93) years. Ethnic distribution was Chinese, 48.9%; Malay, 34.5%; Indian, 14.8%. The prevalence of moderate–severe ED was 20.0%, while 16.1% of men had TDS (<10.4 nmol/L) and 31.3% of men had MS. Indian and Malay men were significantly more likely to have ED (p = 0.001), TDS (p < 0.001) and MS (p < 0.001) than the Chinese. Multivariate regression analysis showed that elevated blood pressure, elevated FBG, low high-density lipoprotein and heart disease were predictors of ED while all MS components were independently associated with TDS. Malay and Indian men have a higher disease burden compared to Chinese men and were more likely to suffer with ED, TDS and MS. MS components were closely related to TDS and ED.

Robotic Assisted Radical Cystectomy with Extracorporeal Urinary Diversion Does Not Show a Benefit over Open Radical Cystectomy: A Systematic Review and Meta-Analysis of Randomised Controlled Trials

Background The number of robotic assisted radical cystectomy (RARC) procedures is increasing despite the lack of Level I evidence showing any advantages over open radical cystectomy (ORC). However, several systematic reviews with meta-analyses including non-randomised studies, suggest an overall benefit for RARC compared to ORC. We performed a systematic review with meta-analysis of randomised controlled trials (RCTs) to evaluate the perioperative morbidity and efficacy of RARC compared to ORC in patients with bladder cancer. Methods Literature searches of Medline/Pubmed, Embase, Web of Science and clinicaltrials.gov databases up to 10th March 2016 were performed. The inclusion criteria for eligible studies were RCTs which compared perioperative outcomes of ORC and RARC for bladder cancer. Primary objective was perioperative and histopathological outcomes of RARC versus ORC while the secondary objective was quality of life assessment (QoL), oncological outcomes and cost analysis. Results Four RCTs (from 5 articles) met the inclusion criteria, with a total of 239 patients all with extracorporeal urinary diversion. Patient demographics and clinical characteristics of RARC and ORC patients were evenly matched. There was no significant difference between groups in perioperative morbidity, length of stay, positive surgical margin, lymph node yield and positive lymph node status. RARC group had significantly lower estimated blood loss (p<0.001) and wound complications (p = 0.03) but required significantly longer operating time (p<0.001). QoL was not measured uniformly across trials and cost analysis was reported in one RCTs. A test for heterogeneity did highlight differences across operating time of trials suggesting that surgeon experience may influence outcomes. Conclusions This study does not provide evidence to support a benefit for RARC compared to ORC. These results may not have inference for RARC with intracorporeal urinary diversion. Well-designed trials with appropriate endpoints conducted by equally experienced ORC and RARC surgeons will be needed to address this.

Early Oncologic Failure after Robot-Assisted Radical Cystectomy: Results from the International Robotic Cystectomy Consortium

Purpose: We sought to investigate the prevalence and variables associated with early oncologic failure. Materials and Methods: We retrospectively reviewed the IRCC (International Radical Cystectomy Consortium) database of patients who underwent robot‐assisted radical cystectomy since 2003. The final cohort comprised a total of 1,894 patients from 23 institutions in 11 countries. Early oncologic failure was defined as any disease relapse within 3 months of robot‐assisted radical cystectomy. All institutions were surveyed for the pneumoperitoneum pressure used, breach of oncologic surgical principles, and techniques of specimen and lymph node removal. A multivariate model was fit to evaluate predictors of early oncologic failure. The Kaplan‐Meier method was applied to depict disease specific and overall survival, and Cox proportional regression analysis was used to evaluate predictors of disease specific and overall survival. Results: A total of 305 patients (22%) experienced disease relapse, which was distant in 220 (16%), local recurrence in 154 (11%), peritoneal carcinomatosis in 17 (1%) and port site recurrence in 5 (0.4%). Early oncologic failure developed in 71 patients (5%) at a total of 10 institutions. The incidence of early oncologic failure decreased from 10% in 2006 to 6% in 2015. On multivariate analysis the presence of any complication (OR 2.87, 95% CI 1.38–5.96, p = 0.004), pT3 or greater disease (OR 3.73, 95% CI 2.00–6.97, p <0.001) and nodal involvement (OR 2.14, 95% CI 1.21–3.80, p = 0.008) was a significant predictor of early oncologic failure. Patients with early oncologic failure demonstrated worse disease specific and overall survival (23% and 13%, respectively) at 1 and 3 years compared to patients who experienced later or no recurrences (log rank p <0.001). Conclusions: The incidence of early oncologic failure following robot‐assisted radical cystectomy has decreased with time. Disease related rather than technical related factors have a major role in early oncologic failure after robot‐assisted radical cystectomy.

Analysis of open and intracorporeal robotic assisted radical cystectomy shows no significant difference in recurrence patterns and oncological outcomes.

OBJECTIVES To report and compare early oncological outcomes and cancer recurrence sites among patients undergoing open radical cystectomy (ORC) and robotic-assisted radical cystectomy with intracorporeal urinary diversion (iRARC). METHODS AND MATERIALS A total of 184 patients underwent radical cystectomy for bladder cancer. ORC cases (n = 94) were performed between June 2005 and July 2014 while iRARC cases (n = 90) were performed between June 2011 and July 2014. Primary outcome was recurrence free survival (RFS). Secondary outcomes were sites of local and metastatic recurrence, cancer specific survival (CSS) and overall survival (OS). RESULTS Median follow-up for patients without recurrence was 33.8 months (interquartile range [IQR]: 20.5-45.4) for ORC; and 16.1 months (IQR: 11.2-27.0) for iRARC. No significant difference in age, sex, precystectomy T stage, precystectomy grade, or lymph node yield between ORC and iRARC was observed. The ORC cohort included more patients with≥pT2 (64.8% ORC vs. 38.9% iRARC) but fewer pT0 status (8.5% ORC vs.vs. 22.2% iRARC) due to lower preoperative chemotherapy use (22.3% ORC vs. 34.4% iRARC). Positive surgical margin rate was significantly higher in the ORC cohort (19.3% vs. 8.2%; P = 0.042). Kaplan-Meir analysis showed no significant difference in RFS (69.5% ORC vs. 78.8% iRARC), cancer specific survival (80.9% ORC vs. 84.4% iRARC), or OS (73.5% ORC vs.vs. iRARC 83.8%) at 24 months. Cox regression analysis showed RFS, cancer specific survival and OS were not influenced by cystectomy technique. No significant difference between local and metastatic RFS between ORC and iRARC was observed. CONCLUSION This study has found no difference in recurrence patterns or oncological outcomes between ORC and iRARC. Recurrent metastatic sites vary, but are not related to surgical technique.

Benefits of robotic cystectomy with intracorporeal diversion for patients with low cardiorespiratory fitness: A prospective cohort study

BACKGROUND Patients undergoing radical cystectomy have associated comorbidities resulting in reduced cardiorespiratory fitness. Preoperative cardiopulmonary exercise testing (CPET) measures including anaerobic threshold (AT) can predict major adverse events (MAE) and hospital length of stay (LOS) for patients undergoing open and robotic cystectomy with extracorporeal diversion. Our objective was to determine the relationship between CPET measures and outcome in patients undergoing robotic radical cystectomy and intracorporeal diversion (intracorporeal robotic assisted radical cystectomy [iRARC]). METHODS A single institution prospective cohort study in patients undergoing iRARC for muscle invasive and high-grade bladder cancer. INCLUSION patients undergoing standardised CPET before iRARC. EXCLUSIONS patients not consenting to data collection. Data on CPET measures (AT, ventilatory equivalent for carbon dioxide [VE/VCO2] at AT, peak oxygen uptake [VO2]), and patient demographics prospectively collected. Outcome measurements included hospital LOS; 30-day MAE and 90-day mortality data, which were prospectively recorded. Descriptive and regression analyses were used to assess whether CPET measures were associated with or predicted outcomes. RESULTS From June 2011 to March 2015, 128 patients underwent radical cystectomy (open cystectomy, n = 17; iRARC, n = 111). A total of 82 patients who underwent iRARC and CPET and consented to participation were included. Median (interquartile range): age = 65 (58-73); body mass index = 27 (23-30); AT = 10.0 (9-11), Peak VO2 = 15.0 (13-18.5), VE/VCO2 (AT) = 33.0 (30-38). 30-day MAE = 14/111 (12.6%): death = 2, multiorgan failure = 2, abscess = 2, gastrointestinal = 2, renal = 6; 90-day mortality = 3/111 (2.7%). AT, peak VO2, and VE/VCO2 (at AT) were not significant predictors of 30-day MAE or LOS. The results are limited by the absence of control group undergoing open surgery. CONCLUSIONS Poor cardiorespiratory fitness does not predict increased hospital LOS or MAEs in patients undergoing iRARC. Overall, MAE and LOS comparable with other series.

Evolution of the neobladder: A critical review of open and intracorporeal neobladder reconstruction techniques

Abstract Orthotopic neobladder is an attractive alternative to the ileal conduit following radical cystectomy. Robotic cystectomy is gaining popularity although the uptake of neobladder reconstruction is low, with the majority of cases being constructed extracorporeally via a mini-laparotomy. Minimally invasive cystectomy using the robotic platform facilitates intracorporeal neobladder reconstruction and several techniques have been described. This review discusses issues relating to patient selection, and describes existing techniques of open surgical neobladder reconstruction and their evolution to suit an intracorporeal approach. A Medline search for publications from January 1970 to September 2015 with the following keyword search criteria was performed: radical cystectomy, robotic cystectomy, intracorporeal, neobladder, orthotopic bladder reconstruction, surgical technique, patient selection and ureteric–ileal anastomosis.