Peter Ka-Fung Chiu

A study based on whole-genome sequencing yields a rare variant at 8q24 associated with prostate cancer

In Western countries, prostate cancer is the most prevalent cancer of men and one of the leading causes of cancer-related death in men. Several genome-wide association studies have yielded numerous common variants conferring risk of prostate cancer. Here, we analyzed 32.5 million variants discovered by whole-genome sequencing 1,795 Icelanders. We identified a new low-frequency variant at 8q24 associated with prostate cancer in European populations, rs188140481[A] (odds ratio (OR) = 2.90; Pcombined = 6.2 × 10−34), with an average risk allele frequency in controls of 0.54%. This variant is only very weakly correlated (r2 ≤ 0.06) with previously reported risk variants at 8q24, and its association remains significant after adjustment for all known risk-associated variants. Carriers of rs188140481[A] were diagnosed with prostate cancer 1.26 years younger than non-carriers (P = 0.0059). We also report results for a previously described HOXB13 variant (rs138213197[T]), confirming it as a prostate cancer risk variant in populations from across Europe.

Genomewide bisulfite sequencing reveals the origin and time-dependent fragmentation of urinary cfDNA

Urinary cell-free (cf) DNA holds great potential as a completely noninvasive form of liquid biopsy. Knowledge of the composition of cfDNA by tissue of origin is useful for guiding its clinical uses. We conducted a global survey of urinary cfDNA composition using genomewide bisulfite sequencing. While previous studies focused on detecting cfDNA from a single source at a time, genomewide tissue specific methylation signatures allow us to simultaneously deduce the proportional contribution from each contributing tissue. The proportional contributions derived from methylation deconvolution are highly correlated with those calculated using allograft-derived donor-specific genetic markers in the urine of hematopoetic stem cell and renal transplant recipients. We found a large variation of proportional contributions from different tissues. We then assessed if cfDNA undergoes time-dependent fragmentation in urine by conducting in vitro incubation experiments. In vitro incubation at 37°C showed that urinary cfDNA concentration decreased under first order kinetics with a half-life of 2.6 to 5.1h. This is reflected in parallel by a decrease in the proportion of long fragments and increase in amplitude of 10bp periodicity seen in the cfDNA size profile. This global survey of urinary cfDNA has deepened our understanding of the composition, degradation and variation of cfDNA in the urinary tract and has laid a foundation for the use of genomewide urinary cfDNA sequencing as a molecular diagnostics tool.

Androgen deprivation therapy, diabetes and poor physical performance status increase fracture risk in Chinese men treated for prostate cancer

Abstract We investigated the fracture risk after androgen deprivation therapy (ADT) for prostate cancer in the Chinese population. All Chinese prostate cancer patients who were treated primarily by radical prostatectomy or radiotherapy, with or without further ADT, from year 2000 to 2009 were reviewed. We compared the fracture risk in patients who were given ADT (ADT group) with those who were not given any ADT (non-ADT group). Potential risk factors including age, diabetes mellitus, hypertension, hyperlipidemia, ischemic heart disease and performance status were reviewed. The fracture risk was analyzed with Kaplan–Meier and multivariate Cox regression analyses. Our cohort consisted of 200 patients in the non-ADT group and 252 patients in the ADT group. The ADT group was shown to have higher fracture risk (p = 0.036) upon Kaplan–Meier analysis. Upon multivariate Cox regression analyses, diabetes mellitus (HR 4.39, 95% CI 1.08–17.83, p = 0.039), poor performance status (HR 3.14, 95% CI 1.24–8.00, p = 0.016) and the use of ADT (HR 4.89, 95% CI 1.03–23.17, p = 0.045) were associated with increased fracture risk. In conclusion, the fracture risk should be considered while deciding on ADT in Chinese men, especially in diabetic patients with poor performance status.

Risk of new-onset diabetes after androgen deprivation therapy for prostate cancer in the Asian population

The associations of androgen deprivation therapy (ADT) with its adverse events in the Asian population remained largely unknown. We investigated the risk of new‐onset diabetes mellitus (DM) after ADT for prostate cancer in the Asian population.

Risk of ischemic stroke after androgen deprivation therapy for prostate cancer in the Chinese population living in Hong Kong

OBJECTIVE Previous reports on the risk of stroke after androgen deprivation therapy for prostate cancer were largely based on Caucasians. We investigated the risk of ischemic stroke after androgen deprivation therapy for prostate cancer in the Chinese population. METHODS All Chinese prostate cancer patients who were treated primarily with radical prostatectomy or radiotherapy, with (androgen deprivation therapy group) or without (non-androgen deprivation therapy group) further androgen deprivation therapy, at our hospital from year 2000-09 were reviewed. Potential risk factors of ischemic stroke including age, baseline prostate-specific antigen, Gleason score, clinical T stage, hypertension, diabetes mellitus, hyperlipidemia, ischemic heart disease, history of stroke, use of androgen deprivation therapy and duration of androgen deprivation therapy were reviewed. The risk of ischemic stroke after androgen deprivation therapy was analyzed with Kaplan-Meier and multivariate Cox regression analyses. RESULTS A total of 452 patients were included, consisting of 200 patients in the non-androgen deprivation therapy group and 252 patients in the androgen deprivation therapy group. The androgen deprivation therapy group appeared to have increased risk of ischemic stroke when compared with the non-androgen deprivation therapy group (P = 0.063) upon Kaplan-Meier analysis. Upon multivariate Cox regression analyses, older age (hazard ratio 1.13, 95% confidence interval 1.04-1.22, P = 0.003), hyperlipidemia (hazard ratio 4.61, 95% confidence interval 2.01-10.54, P < 0.001) and the use of androgen deprivation therapy (hazard ratio 3.32, 95% confidence interval 1.14-9.67, P = 0.028) were associated with increased risk of ischemic stroke. CONCLUSIONS There was increased risk of ischemic stroke after androgen deprivation therapy for prostate cancer in the Chinese population. The risk of ischemic stroke should be considered while deciding on androgen deprivation therapy, especially in older patients with known history of hyperlipidemia.

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.

Case-Control Study of Intra-arterial Verapamil for Intraprostatic Anastomoses to Extraprostatic Arteries in Prostatic Artery Embolization for Benign Prostatic Hypertrophy.

PURPOSE It is hypothesized that intra-arterial administration of verapamil is a safe and effective way to reverse the flow in intraprostatic anastomoses to extraprostatic arteries without compromising treatment outcomes in prostatic artery embolization (PAE) for benign prostatic hypertrophy (BPH). MATERIALS AND METHODS A prospective study of 62 prostate sides in 31 consecutive patients (median age, 66 y; range, 60-71 y) with symptomatic BPH was undertaken. Median prostate volume was 72.4 mL (range, 48.8-85.8 mL), median International Prostate Symptom Score was 21 (range, 15-23), and median urine peak flow rate was 4 mL/s (range, 2-6 mL/s). The arterial anastomoses were classified as types I-III according to vascular morphology. Treatment safety was assessed in terms of adverse events and complications, and treatment effectiveness was assessed in terms of success rate of angiographic flow reversal. RESULTS The PAE procedure was successfully completed in all 31 patients (100%). Adverse events in both groups were transient and mild and did not necessitate prolonged hospitalization. There was no clinical evidence of any significant nontarget ischemic complication in either group. Intraprostatic anastomosis was diagnosed in 19 of 31 patients (61.3%) and 22 of 62 prostate sides (35.5%). Success rates of verapamil treatment were 88.9% overall (20 of 22) and 100% (19 of 19) in type II and III anastomoses. There was no difference between the treatment group and the control group in clinical, urologic, and imaging outcomes of PAE. CONCLUSIONS Intra-arterial verapamil treatment was probably safe and effective in causing flow reversal in type II and III intraprostatic anastomoses and in preventing ischemic complications in PAE for BPH without compromising PAE outcomes.

“Aging males” symptoms and general health of adult males: a cross-sectional study

Abstract A cross-sectional study was conducted to explore the prevalence and severity of health-related complaints perceived by adult males of Hong Kong by using the Hong Kong Traditional Chinese versions of the Aging males’ symptoms (AMS) scale and the 5-dimensional and 3-level European Quality of life (EQ-5D-3L) questionnaire. A total of 825 adult males aged 40 years or above were surveyed, and observed that 80% of the population was living with little-to-mild levels of aging symptoms with mean total scores ranged between 26.02 ± 7.91 and 32.99 ± 7.91 in different age groups. Such symptoms were correlated with age, especially for the somato-vegetative and sexual symptoms. The most severe AMS symptoms were observed in the oldest age group at 70 years or above, with 76%, 34% and 70% living with moderate-to-severe levels of somato-vegetative, psychological and sexual symptoms, respectively. The result was highly correlated with the EQ-5D-3L questionnaire. Secondly, the Hong Kong Aging males’ symptoms (AMS) scale was shown to have good reliability with test–retest coefficient at 0.79 (ranged 0.66–0.87) and Cronbach’s alpha coefficient at 0.88 (ranged 0.70–0.84). In summary, the population of Hong Kong male adults was commonly living with little-to-mild levels of aging symptoms, whereas their severity was correlated with age.

The effect of renal cortical thickness on the treatment outcomes of kidney stones treated with shockwave lithotripsy.

Purpose Because the shock wave passes through various body tissues before reaching the stone, stone composition may affect the treatment efficacy of shock wave lithotripsy (SWL). We investigated the effect of various tissue components along the shock wave path on the success of SWL. Materials and Methods From October 2008 to August 2010, a total of 206 patients with kidney stones sized 5 to 20 mm were prospectively recruited for a study of the factors that affect the outcome of treatment with a Sonolith Vision lithotripter. Successful SWL was defined as either stone-free status or residual fragments <4 mm at 12 weeks. Logistic regression analysis was performed to assess the factors that predicted treatment outcomes. Potential predictors included the patients age, shock wave delivery rate, stone volume (SV), mean stone density (MSD), skin-to-stone distance (SSD), and the mean thickness of the three main components along the shock wave path: renal cortical thickness (KT), muscle thickness (MT), and soft-tissue thickness (ST). Results The mean age of the patients was 53.8 years (range, 25-82 years). The overall treatment success rate after one session of SWL was 43.2%. The mean KT, MT, and ST were 26.9, 16.6, and 40.8 mm, respectively. The logistic regression results showed that a slower shock wave delivery rate, smaller SV, a lower MSD, and a thicker KT were found to be significant predictors for successful SWL. SSD, MT, and ST were not predictors of successful treatment. Conclusions Among the main tissue components along the shock wave path, a thicker KT was a favorable factor for successful SWL after adjustment for SV, MSD, and the shock wave delivery rate.

Secondary hemorrhage after bipolar transurethral resection and vaporization of prostate

Introduction: We evaluated the factors associated with secondary hemorrhage after bipolar transurethral resection of prostate (TURP) and vaporization of prostate. Materials and Methods: The perioperative data of patients undergoing endoscopic surgery for benign prostatic hyperplasia (BPH) were prospectively collected. Procedures involved included bipolar TURP, bipolar vaporization of prostate, and hybrid bipolar TURP/vaporization of prostate. Secondary hemorrhage was defined as bleeding between 48 h and 30 days postsurgery requiring hospital attendance with or without admission. Risk factors for secondary hemorrhage were analyzed. Results: From 2010 to 2013, 316 patients underwent bipolar surgery for BPH. Bipolar TURP accounted for 48.1% of the procedures, bipolar vaporization accounted for 20.3% of the procedures, and the rest were hybrid TURP/vaporization of prostate. Among this cohort of patients, fifty patients had secondary hemorrhage with hospital attendance. Consumption of platelet aggregation inhibitors (PAIs) was found to be associated with secondary hemorrhage (P < 0.0005). Age, prostate volume, operation type, the use of 5-alpha reductase inhibitors, and being with a urethral catheter before operation were not found to be statistically significant risk factors for secondary hemorrhage. Conclusions: Secondary hemorrhage after bipolar surgery for BPH is a common event. Consumption of PAI is a risk factor for such complication.