In vitro assessment of intra-operative and post-operative environment in reducing bladder cancer recurrence.

Urinary bladder cancer is a common cancer worldwide. Currently, the modality of treating and monitoring bladder cancer is wide. Nonetheless, the high recurrence rate of non-muscle-invasive bladder cancer after surgical resection is still unsatisfactory. Hereby, our study demonstrated whether the intra-operative and post-operative environments will affect bladder cancer recurrence utilizing in vitro cell line model. Bladder cancer cell lines were submerged in four different irrigating fluids for assessing their tumorigenic properties. Our results showed that sterile water performed the best in terms of the magnitude of cytotoxicity to cell lines. Besides, we also investigated cytotoxic effects of the four irrigating agents as well as mitomycin C (MMC) in normothermic and hyperthermic conditions. We observed that sterile water and MMC had an increased cytotoxic effect to bladder cancer cell lines in hyperthermic conditions. Altogether, our results could be translated into clinical practice in the future by manipulating the intra-operative and post-operative conditions in order to lower the chance of residual cancer cells reimplant onto the bladder, which in turns, reducing the recurrence rate of bladder cancers.

eLearning and transurethral prostate surgery: virtual tools for a real training.

PURPOSE OF REVIEW: In the recent two decades, technological breakthrough has tremendously expanded the scope of transurethral prostate surgery. New gadgets and energy devices keep emerging to tackle benign prostatic obstruction, which was dealt with mainly by transurethral resection of prostate in the old days. Although this trend appears fascinating, it also means that urologists need quality training to attain surgical safety in performing these new surgeries. E-learning and simulation training may play an important role in modern urology training. RECENT FINDINGS: In this review, we would describe, using up-to-date evidence, the key components of simulation training, the types of simulators currently in use and their respective advantages and limitations. SUMMARY: Modern simulation technology enables surgical training in a realistic, reproducible and risk-free environment. Simulation training has been proven to improve both performers' confidence and objective scores in various transurethral prostate surgeries. Its use should therefore be advocated.

Sectoral cancer detection and tolerability of freehand transperineal prostate biopsy under local anaesthesia.

BACKGROUND: To investigate the feasibility of a freehand transperineal (TP) systematic prostate biopsy protocol under local anaesthesia (LA) and the value of different sectors in diagnosing prostate cancer (PCa). METHODS: A total of 611 consecutive freehand TP biopsies under LA in 2 hospitals were prospectively evaluated. Cancer detection rate in each of the four different sectors (anterior, mid, posterior, basal) was recorded to evaluate the value of each sector. Procedure tolerability was assessed by pain score and complications were documented. RESULTS: Systematic biopsies were performed in 556 out of 611 men with a median of 20 (IQR 12-24) biopsy cores taken. The median PSA was 9.9 (Inter-quartile range[IQR] 6.4-16.2) ng/mL, and 89.0% were first biopsies. All PCa and ISUP grade group (GG) ≥ 2 PCa (HGPCa) were diagnosed in 41.4% (230/556) and 28.2% (157/556) biopsies respectively. 77.0% HGPCa was diagnosed in ≥2 sectors. Single-sector HGPCa was predominantly found in anterior or posterior sector. Omitting base sector would have missed 1.5% (1/65) HGPCa out of the 219 cases with ≥24-core biopsies performed. Further omission of mid sector would have missed 3.1% (2/65) HGPCa and 7.4% (7/94) ISUP GG1 PCa (in which 3/7 involved 2 sectors). LA TP biopsy was well tolerated and the mean pain scores of the different steps of the procedure were between 1.9-3.1 (out of 10). Post-biopsy fever occurred in 0.3% of patients (2/611) and no sepsis was reported. The risk of urinary retention in men with ≥20 cores in ≥60 ml prostate was 7.8% (14/179), compared with 1.7% (7/423) in other groups (p < 0.001). CONCLUSIONS: TP sectoral prostate biopsy under LA was well tolerated with minimal sepsis risk. Basal sector biopsies had minimal additional value to HGPCa detection and its omission can be considered.

Surgical training for anatomical endoscopic enucleation of the prostate.

Anatomical endoscopic enucleation of the prostate has been proposed as a potentially superior benign prostatic hyperplasia surgery than conventional transurethral resection of prostate. However, the learning curve of the procedure is steep, hence limiting its generalisability worldwide. In order to overcome the learning curve, a proper surgical training is extremely important. This review article discussed about various aspects of surgical training in anatomical endoscopic enucleation of the prostate. In summary, no matter what surgical technique or energy modality you use, the principle of anatomical enucleation should be followed. When one starts to perform prostate enucleation, a 50 to 80 g prostate appears to be the 'best case' to begin with. Mentorship is extremely important to shorten the learning curve and to prevent drastic complications from the procedure. A proficiency-based progression training programme with the use of simulation and training models should be the best way to teach and learn about prostate enucleation. Enucleation ratio efficacy is the preferred measure for assessing skill level and learning curve of prostate enucleation. Morcellation efficiency is commonly used to assess morcellation performance, but the importance of safety rather than efficiency must be emphasised.

Transurethral resection of prostate for acute urinary retention is linked to shorter survival in younger men.

It is largely unknown whether lower urinary tract symptoms (LUTS) or acute retention of urine (AROU) is linked to shorter life expectancy in men. We conducted a multicenter, retrospective database analysis of patients undergoing transurethral resection of prostate (TURP) to study their relationships. Multivariate Cox regression analysis and Kaplan-Meier analysis with stratification to age and indication of TURP were performed. We further performed an age- and sex-matched survival analysis with the general population using data from the Census and Statistics Department of the Hong Kong Special Administrative Region (Hong Kong, China). From January 2002 to December 2012, 3496 patients undergoing TURP were included in our study, with 1764 patients in the LUTS group and 1732 patients in the AROU group. Old age, ischemic heart disease, cerebrovascular accident, and AROU were risk factors of mortality. Patients aged <70 years (adjusted hazard ratio [HR]: 1.52, 95% confidence interval [CI]: 1.11-2.09, P = 0.010) and 70-80 years (adjusted HR: 1.39, 95% CI: 1.15-1.70, P = 0.001) in the AROU group had worse survival than those in the LUTS group, but such difference was not demonstrated in patients aged >80 years. Compared to the general population, younger patients in the LUTS group appeared to have better survival (<70 years, P = 0.091; 70-80 years, P = 0.011), but younger patients in the AROU group had worse survival (<70 years, P = 0.021; 70-80 years, P = 0.003). For patients aged >80 years, survival was similar with the general population in both the LUTS and AROU groups. In conclusion, AROU at young age was associated with mortality, while early detection and management of LUTS may improve survival.

The Role of Vitamin D Receptor Polymorphisms in Predicting the Response to Therapy for Nonmuscle Invasive Bladder Carcinoma.

PURPOSE: Clinical and pathological predictors of bladder carcinoma recurrence and progression are relatively well defined. However, there is a paucity of genetic data specifically on the association of single nucleotide polymorphisms in specific genes for predicting recurrence and progression following immunotherapy. The VDR gene was found to regulate the immunomodulatory effects of vitamin D and it enhances the innate immunity system. We evaluated 3 VDR single nucleotide polymorphisms and their predictive role on the response to immunotherapy. MATERIALS AND METHODS: Patients with bladder cancer at intermediate-high risk who underwent post-transurethral resection intravesical bacillus Calmette-Guérin in Singapore and Hong Kong from 1995 to 2014 were recruited for analysis. We evaluated 3 VDR single nucleotide polymorphisms using polymerase chain reaction. Kaplan-Meier survival curves and relationships with outcomes were analyzed by multivariable Cox regression. RESULTS: A total of 338 predominantly Chinese patients were included in study. Individuals carrying the VDR genotype Bsm A/G were significantly associated with lower time to recurrence after bacillus Calmette-Guérin therapy (p <0.001). On multivariable analysis the HR of recurrence in patients with the Bsm A allele was 3.95 times that in patients without the allele (p = 0.037). Patients with the VDR GATC subhaplotype were 3.05 times more likely than patients with other subhaplotypes to experience recurrences (p = 0.003). Study limitations include the small sample size and the lack of information on previous bacillus Calmette-Guérin vaccine exposure and on vitamin D levels. CONCLUSIONS: Our findings in this study suggest that various VDR single nucleotide polymorphisms are associated with recurrences after bacillus Calmette-Guérin immunotherapy. Further functional studies should be performed to elucidate the significance of the VDR gene in the management of bladder cancer and the potential therapy implications.

Bisphenol A and other environmental risk factors for prostate cancer in Hong Kong.

BACKGROUND: Environmental exposures are contributing factors to prostate cancer etiology, but these remain unclear. We aimed to document the associations between environmental risk factors and prostate cancer in Chinese, with special reference to bisphenol A (BPA). METHODS: We recruited 431 newly diagnosed prostate cancer cases and 402 age-matched controls from Prince of Wales Hospital in Hong Kong. We obtained each participant's clinical data and epidemiological information on chronic BPA exposure and other environmental risk factors (e.g., dietary habits, occupation and shift work) using a standard questionnaire. A new assessment tool of environmental BPA exposure was developed and replicated. Multiple logistic regression analysis was performed to examine odds ratio (OR) and 95% confidence interval (95% CI) for the association of prostate cancer with a novel cumulative BPA exposure index (CBPAI) and other environmental risk factors. RESULTS: Weekly consumption of deep fried food (OR=1.85, 95% CI: 1.15-2.95) and pickled vegetable (OR=1.87, 95% CI: 1.07-3.28) was significantly associated with excessive prostate cancer risk. Prostate cancer was positively associated with nightshift work (OR=1.76, 95% CI: 1.07-2.89) and it was negatively associated with green tea drinking (OR=0.56, 95% CI: 0.34-0.91). There was a positive exposure-response relationship between CBPAI and prostate cancer, with the greatest and significant risk in the high versus reference category (OR=1.57, 95% CI: 1.01-2.44). CONCLUSIONS: Frequent consumption of deep fried food and pickled vegetable, non-habitual green tea drinking and nightshift work are the contributing risk factors to prostate cancer in Hong Kong Chinese. More importantly, this study provides the first epidemiological evidence on carcinogenicity of BPA on the human prostate.

Short-stay transurethral prostate surgery: A randomized controlled trial comparing transurethral resection in saline bipolar transurethral vaporization of the prostate with monopolar transurethral resection.

OBJECTIVES: The aim of the present study was to establish the safety and efficacy profile of transurethral resection in saline (TURis) bipolar vaporization of the prostate relative to monopolar transurethral resection of prostate (TURP) and to test the hospital stay efficiency after TURis vaporization. MATERIALS AND METHODS: in this multicenter, double-blinded, prospective, randomized controlled trial, men aged 50-75 years old were randomized into two arms: TURis bipolar vaporization and monopolar TURP. Intraoperative details, perioperative parameters, and postoperative functional outcomes were assessed after intervention. Follow-up with symptom score assessment, prostate volume measurement, and uroflowmetry were performed at 3 and 6 months. RESULTS: Eighty-four patients (mean age, 65.0 ± 5.6 years) were randomized into each study arm. TURis bipolar vaporization had a longer operative time than monopolar TURP (51.6 ± 24.5 vs 38.5 ± 20.3 min, P < 0.001). Postoperatively, the TURis group had a shorter catheter time (33.6 ± 23.7 vs 40.8 ± 29.4 h, P = 0.013) and a shorter length of hospital stay (43.14 ± 18.79 vs 52.33 ± 30.58 h, P = 0.013). The postoperative dysuria score was higher in the TURis vaporization arm. There was no statistically significant difference between the two arms in terms of hemoglobin change and postoperative complication. No significant difference was observed in quality of life score at 3 and 6 months. CONCLUSIONS: TURis bipolar vaporization of the prostate is a safe and comparable alternative to monopolar TURP. It leads to a reduction in both catheter time and length of hospital stay.

Ginsenoside Rb3 attenuates oxidative stress and preserves endothelial function in renal arteries from hypertensive rats.

BACKGROUND AND PURPOSE: Panax ginseng is commonly used to treat cardiovascular conditions in Oriental countries. This study investigated the mechanisms underlying the vascular benefits of ginsenoside Rb3 (Rb3) in hypertension. EXPERIMENTAL APPROACH: Rings of renal arteries were prepared from spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats and were cultured ex vivo for 8 h. Contractile responses of the rings were assessed with myograph techniques. Expression of NADPH oxidases was assessed by Western blotting and immunohistochemistry. Reactive oxygen species (ROS) were measured using dihydroethidium fluorescence imaging and production of NO was determined using the fluorescent NO indicator DAF-FM diacetate in human umbilical vein endothelial cells. KEY RESULTS: Ex vivo treatment with Rb3 concentration-dependently augmented endothelium-dependent relaxations, suppressed endothelium-dependent contractions and reduced ROS production and expressions of NOX-2, NOX-4 and p67(phox) in arterial rings from SHR. Rb3 treatment also normalized angiotensin II (Ang II)-stimulated elevation in ROS and expression of NOX-2 and NOX-4 in arterial rings from WKY rats. Rb3 inhibited Ang II-induced reduction of NO production and phosphorylation of endothelial NOS in cultures of human umbilical vein endothelial cells. Rb3 also inhibited oxidative stress in renal arterial rings from hypertensive patients or in Ang II-treated arterial rings from normotensive subjects. CONCLUSION AND IMPLICATIONS: Ex vivo Rb3 treatment restored impaired endothelial function in arterial rings from hypertensives by reversing over-expression of NADPH oxidases and over-production of ROS, and improved NO bioavailability. Our findings suggest that medicinal plants containing Rb3 could decrease oxidative stress and protect endothelial function in hypertension.

Synergistic Cytotoxic Effects of Ganoderma lucidum and Bacillus Calmette Guérin on Premalignant Urothelial HUC-PC Cells and Its Regulation on Proinflammatory Cytokine Secretion.

Bacillus Calmette-Guérin (BCG) is conventionally used as an adjuvant immunotherapy to reduce the recurrence of bladder cancer. To address the issues of efficacy and safety, an ethanol extract of Ganoderma lucidum (GLe) was evaluated for its interaction with BCG. In a model of premalignant human uroepithelial cells (HUC-PC), GLe exerted immediate cytotoxic effects while BCG showed a delayed response, given that both were immunological active in inducing the secretion of interleukin (IL)-6, IL-8, and monocyte chemotactic protein-1 (MCP-1). Synergistic cytotoxic effects were observed when cells were either coincubated with both drugs or firstly preincubated with GLe. Synergism between GLe and BCG was demonstrated to achieve a complete cytostasis in 24 hours, and such effects were progressed in the subsequent 5 days. However, the pretreatment of GLe resulted in suppression of IL-6, IL-8, and MCP-1 secretions without affecting the cytotoxicity. Given that numerous proinflammatory cytokines are associated with the high side effects toll of BCG, results herein suggested the potential implications of GL to supplement the BCG immunotherapy in bladder cancer, for better efficacy and reducing side effects.

Randomized controlled trial of antibiotic prophylaxis regimens for transrectal ultrasound-guided prostate biopsy.

BACKGROUND: A prior study showed significant antibiotic resistance to quinolone in our population. In this study we aimed to evaluate and compare the efficacy of a single versus a combined prophylactic antibiotic regimen before transrectal ultrasound-guided prostate biopsy (TRUGPB). METHODS: A prospective randomized study was conducted at a university hospital. Patients undergoing TRUGPB were randomized into an amoxicillin-clavulanate alone (1 mg; one dose before and two doses after biopsy) or an amoxicillin-clavulanate + ciprofloxacin group (250 mg; one dose before and two doses after biopsy). Patients were surveyed for infection symptoms by phone on days 3 and 30 after TRUGPB. We defined an infective complication as the occurrence of symptoms including fever, chills or rigor within 30 days after prostate biopsy, requiring medical treatment or hospitalization, aided by a territory-wide electronic medical record system. RESULTS: Between November 2007 and July 2009, 367 patients were randomized to either amoxicillin-clavulanate alone or amoxicillin-clavulanate + ciprofloxacin group. The infection rates after TRUGPB were 3.91% in the former group (7 out of 179 patients) versus 0.53% (1 out of 188 patients) in the latter. Sixty-three percent (5/8) of patients with infective complications needed hospitalization. There was no intensive care unit admission or mortality during the study period. CONCLUSIONS: Combining prophylactic antibiotics with amoxicillin-clavulanate + ciprofloxacin significantly reduced the incidence of infective complications after TRUGPB. We recommended a combination regimen, especially in centre with high incidence of post-TRUGPB infection.

A randomized controlled trial comparing the efficacy of hybrid bipolar transurethral vaporization and resection of the prostate with bipolar transurethral resection of the prostate.

BACKGROUND AND PURPOSE: In comparison with monopolar transurethral resection of the prostate (TURP), bipolar TURP has been shown to have similar efficacy and complication profiles. Whether the hybrid technique of bipolar resection and vaporization of the prostate further improves catheterization time, dysuria, and complication profiles has not been defined, however. The objective of this study was to compare the efficacy and safety profile of bipolar hybrid prostate surgery using both resection and vaporization modes, with bipolar resection undertaken using the transurethral resection in saline bipolar system. PATIENTS AND METHODS: This was a randomized controlled trial that compared bipolar hybrid surgery and bipolar resection of the prostate among men aged ≥ 50 years with benign prostatic hyperplasia (BPH) whose course of medical therapy had failed or who had recurrent urinary retention (CUHK_CCT00623). Patients were randomly assigned to receive either bipolar hybrid surgery or bipolar resection of the prostate. Both patients and assessors were blinded to the type of surgery performed. The primary study end point was catheter time. The secondary end points included postoperative hospital stay and dysuria score. We report the interim results for 86 patients. RESULTS: Forty-six patients were in the hybrid group and 40 were in the resection group. There were no differences between the two groups in prostate volumes (61.5 cc, standard deviation [SD]=34.5 vs 61.0 cc, SD=23.8), preoperative prostate-specific antigen levels (8.7 ng/mL, SD=8.5 vs 9.5 ng/mL, SD=8.4), or preoperative retention status (56.5% vs 70%). The mean operative time was 46.2 minutes for the hybrid group (SD=20.2) and 39.2 minutes for the resection group (SD=17.5). The hybrid group had a significantly shorter postoperative catheter time (34.5 h, SD=15.8 vs 44.7 h, SD=24.5, P=0.027). There was a significant difference between the two groups in the postoperative pain score on day 1 postsurgery (3.5 in the hybrid group vs 1.0 in the resection group, P=0.028). There was no difference between the groups in terms of changes in serum hemoglobin and serum sodium levels or the reintervention rate. All patients voided well after operation, with maximal flow improvements of 9.9 mL/s (SD 8.1) and 8.2 mL/s (SD 10.0) for the hybrid and resection groups, respectively, 1 month postsurgery. CONCLUSION: Transurethral bipolar resection and vaporization of the prostate reduces catheterization time and facilitates postoperative care.