Genetic investigations on causes of male infertility in Western Saudi Arabia.

In recent years, genetic studies have yielded great progress in elucidating causes of male infertility. This investigation aims to identify frequent genetic abnormalities, that is, sex chromosome aneuploidies and Y-chromosome microdeletions among infertile men in Western Saudi Arabia. From a population of infertile patients, 88 male patients with either azoospermia or severe oligozoospermia (sperm concentration <5 million/ml) were selected. In addition to a thorough clinical workup, karyotypes and Y-chromosomal microdeletions were investigated. Among those 88 infertile patients, we detected six patients with Klinefelter syndrome, two with 47 XYY syndrome and two with Y-chromosome microdeletions AZFb,c. While the prevalence of sex chromosome aneuploidies was in the range of globally investigated populations, the microdeletions appeared to be less frequent in Western Saudi Arabia compared to other regions of the world. All genetically abnormal cases showed sperm concentration <1 million/ml, and hence, this appears to be the threshold for warranting genetic investigations in Western Saudi Arabia. Since Klinefelter and 47 XYY syndromes were only discovered late in life, upon an infertility investigation, sex chromosome aneuploidies due to their many-fold comorbidities require earlier medical attention. A neonatal screening programme is suggested for detection of these aneuploidies in Saudi Arabia for the general health benefit of these patients.

Extragastrointestinal stromal tumor of prostate.

Gastrointestinal stromal tumors (GISTs) that originate outside the GI tract are extremely uncommon. In this case report, we describe a GIST of primary origin in the prostate gland of an 84-year-old male who presented with severe urinary retention at King Abdulaziz University Hospital in Saudi Arabia. Diagnosis was based on patient history, radiological studies, pathologic findings, and immunohistochemical data. Digital rectal examination revealed a hugely enlarged prostate encroaching upon the rectal lumen with a smooth and firm surface. Transrectal ultrasound showed a markedly enlarged prostate with an estimated volume of 360 ml; prostate-specific antigen was 5.4 ng/ml. Immediate preoperative cystoscopy demonstrated only a moderate enlargement of the prostate, which was disproportionate to its actual size. Postoperative abdominal computed tomography showed residual prostatic tissue with an estimated weight of 78 g, multiple diffuse colonic diverticulosis, and scattered subcentimeter mesenteric lymph nodes. Histopathological examination of the prostatic tissue showed cellular spindle cell neoplastic proliferation which was diffusely positive for CD117 (c-kit), DOG1, and CD34. GISTs must be considered in the differential diagnosis of spindle cell tumors detected in the prostate.

Treatment of refractory category III nonbacterial chronic prostatitis/chronic pelvic pain syndrome with intraprostatic injection of onabotulinumtoxinA: a prospective controlled study.

INTRODUCTION: To evaluate the efficacy and safety of intraprostatic injections of onabotulinumtoxinA (onaBoNT-A) to treat refractory chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). MATERIALS AND METHODS: Prospective two-group controlled study. Treatment group included adult men with refractory category-III nonbacterial CP/CPPS who underwent transurethral intraprostatic injections of onaBoNT-A (200 U). Control group included comparable patients who underwent cystoscopy only. Primary outcome was the proportion of 6-point responders (≥ 6 points reduction of total score of National Institutes of Health-Chronic Prostatitis Symptom Index [NIH-CPSI]), at 3 months. Secondary outcomes included proportions of quality of life (QoL) responders (≤ 2 points in QoL domain), and global response assessment (GRA) responders (patients reporting moderately improved, or markedly improved), at 3 months. Other outcomes comprised changes from baseline NIH-CPSI scores, visual analog scale (VAS) sub-score of pain domain, PSA, prostate volume, post-void residual urine, and maximum flow rate. Significance was set at p < 0.05. RESULTS: Treatment group included 43 patients with mean age (SD) of 38.8 (7.3) years and mean duration of symptoms of 7.0 (2.9) years. At 3 months, the proportions of responders (NIH-CPSI 6-point, QoL, and GRA) were 72.1%, 69.8%, and 72.1%; which gradually declined to 37.2%, 25.7% and 27.9%, respectively, at 12 months. The baseline NIH-CPSI total score demonstrated -68.2% reduction at 3 months (-20.1 points; p < 0.0001); which gradually waned to -19% reduction (-5.6 points; p < 0.0001) at 12 months. Baseline VAS showed -79%, and -27.4% reductions at 3 and 12 months, respectively (p < 0.0001, each). None of control men has been 6-point, QoL nor GRA responder and none has demonstrated significant NIH-CPSI scores changes from baseline (p > 0.05, each). Compared to control, mean NIH-CPSI total scores of treated men at 1 and 3 months were significantly different (p < 0.001, each). CONCLUSION: OnaBoNT-A intraprostatic injections appeared to be effective and safe to ameliorate symptoms of refractory nonbacterial CP/CPPS; with pain most improved. The improvements gradually dwindled at 9-12 months.

Novel augmentation ileocystoplasty technique to manage non-compliant bladders in the presence of obstructed megaureters: the "fez procedure".

OBJECTIVES: To show the efficacy and safety of a novel modification of Studer's neobladder, herein defined as the "fez procedure." METHODS: The medical records of 21 children (mean age 9.4 ± 1.3 years) who underwent the "fez procedure" at King Abdulaziz University Hospital, Jeddah, Saudi Arabia, to manage refractory poorly-compliant bladders and concomitantly obstructed megaureters were retrospectively reviewed. The patients had been previously managed by either preliminary cutaneous ureterostomy (17 patients) or temporary nephrostomy (four patients) to improve and stabilize the renal functions. The "fez procedure" entailed augmentation ileocystoplasty and the use of an afferent tubularized ileal loop for direct ureteroileal anastomosis. The augmented bladder together with the tubularized loop were fashioned as a "fez" with its tassel. The outcome measures were changes in cystometric capacity, bladder compliance, glomerular filtration rate, serum creatinine, technetium 99m-diethylene triamine pentaacetic acid diuretic renography (T1/2), ureteral diameter, vesicoureteral reflux, febrile urinary tract infections, continence and complications. RESULTS: The mean study follow-up period was 52.5 ± 12.8 months. Means of changes of cystometric capacity (273.2 ± 60.9 mL) and bladder compliance (15.6 ± 4.2 mL/cm H2 O) were significant (P < 0.0001). Resolution of ureteral obstruction was documented with improved T1/2 and ureteral diameter (P < 0.0001, each) of all patients. The initially improved renal functions after ureterostomies or nephrostomies were maintained after "fez surgery," with non-significant changes in the improved glomerular filtration rate (P = 0.22) and serum creatinine (P = 0.18). None of the patients experienced ureteral restenosis, vesicoureteral reflux, febrile urinary tract infections, incontinence or significant complications. CONCLUSIONS: The "fez procedure" represents a versatile and successful surgical option for these selected patients, as it offers improved bladder capacity/compliance, resolution of ureteral obstruction and vesicoureteral reflux, preservation of the renal function, control of urinary tract infections and urinary continence, and acceptable morbidity.

Effects of varicocele on serum testosterone and changes of testosterone after varicocelectomy: a prospective controlled study.

OBJECTIVE: To examine the hypotheses that clinical varicoceles affect baseline serum total testosterone levels (T) and varicocelectomy improves T. MATERIALS AND METHODS: This prospective, nonrandomized, controlled study involved 4 groups of adult men. Varicocele-infertile treatment group (VIT) included 66 men who underwent varicocelectomy. Thirty-three varicocele-infertile control men (VIC) and 33 varicocele-fertile control men (VFC) were only observed. Normal-control (NC) group included 33 fertile men without varicocele. Varicocele groups were stratified into baseline hypogonadal (T <300 ng/dL) or eugonadal (T ≥300 ng/dL) subgroups. Main outcome measurements were between-group baseline T differences; and within-group T changes at 6- and 12-month follow-ups of men with varicocele. P <.05 was considered significant. RESULTS: Means (standard deviations) of baseline T in VIT, VIC, VFC, and NC were 347.4 (132.1), 339.7 (125.8), 396.6 (164.9), and 504.8 (149.7) ng/dL, respectively. The baseline T levels of varicocele groups were comparable, whereas they were significantly low compared with NC group. At 6-month follow-up, VIT demonstrated significant T improvements (mean change = 44.7 ng/dL; 12.9%; P <.0001). T changes were more remarkable among baseline hypogonadals (mean change = 93.7 ng/dL; 40.1%; P <.0001) compared with eugonadals (mean change = 8.6 ng/dL; 2.01%; P = .1223). These improvements were persistent at 12-month follow-up. Contrariwise, VIC and VFC exhibited nonsignificant T changes. Postvaricocelectomy T changes correlated significantly and inversely with baseline T (r = -0.689; P <.0001). This correlation was stronger and more significant among hypogonadals (r = -0.528; P = .004) than eugonadals (r = -0.400; P = .013). T improvements also exhibited significant positive correlations with preoperative and postoperative sperm concentrations. CONCLUSION: Baseline T was significantly low in men with varicocele compared with normal men. Varicocelectomy yielded significant T improvements among hypogonadal men but insignificant changes in eugonadals. T changes correlated strongly and significantly with baseline T and sperm concentrations.

Photoselective vaporization of the prostate using GreenLight 120-W lithium triborate laser to treat symptomatic benign prostatic hyperplasia: A single-centre prospective study.

OBJECTIVE: We evaluated the safety and efficacy of photoselective vaporization of the prostate (PVP) using GreenLight 120-W lithium triborate (LBO) laser to treat symptomatic small-to-medium sized benign prostatic hyperplasia (BPH). METHODS: This prospective non-controlled observational study included symptomatic BPH men ≥50 years with international prostate symptom score (IPSS) ≥14, prostate volume (PV) ≤80 cc and maximum flow rate (Q-max) ≤15 mL/s. PVP was performed using the GreenLight 120-W LBO laser machine. Patients were assessed at baseline and postoperatively at discharge, 2 weeks, and 3, 6 and 12 months. We measured changes in IPSS, PV, PSA, Q-max, post-void residual (PVR), hemoglobin (Hb), serum sodium (Na+) and reported complications. Statistical significance was p < 0.05. RESULTS: The study included 103 men with mean age of 67 (±standard deviation)±9.7 years. Thirty patients were on indwelling urethral catheters for refractory urinary retention and 12 on ongoing anticoagulants. The mean baseline IPSS, PV, PSA, Q-max and PVR parameters significantly improved at follow-up (p < 0.001; each). Mean measurements at baseline versus at six months were: IPSS 25.6 ± 4.2 vs. 7.4±2.3; PV 44.6 ± 9.2 vs. 21.6 ± 6.3 cc (51.6% reduction); Q-max 5.8 ± 3.4 vs. 20.4 ± 4.8 mL/s; PVR 110 ± 40 vs. 35 ± 9 cc. Mean baseline Hb and serum Na+ declined non-significantly (p > 0.05) at discharge and at 2 weeks. No patient needed a blood transfusion. Secondary procedures were needed in 2 patients for urethral and bladder neck strictures. The re-treatment rate for residual adenoma was 0.97%. CONCLUSION: PVP using the GreenLight 120-W LBO laser to treat small-to-medium sized symptomatic BPH demonstrated significant improvements in efficacy parameters and high safety profile within 12 months of follow-up. The procedure entails good hemostasis with minimal blood loss even in patients receiving ongoing anticoagulants.

Predictors of sperm recovery and azoospermia relapse in men with nonobstructive azoospermia after varicocele repair.

PURPOSE: In this study we determined the recoverability and sustainability of motile sperm in semen of men with nonobstructive azoospermia after varicocelectomy as related to different variables. MATERIALS AND METHODS: Men with documented infertility for more than 1 year, with nonobstructive azoospermia and clinically palpable varicoceles were included in this prospective noncontrolled study. Participants underwent simultaneous subinguinal microsurgical varicocelectomy and testicular biopsies. Preoperative as well as initial and late followup semen analyses were performed. Outcomes of sperm recovery and relapse of azoospermia were correlated with the variables of patient age, infertility duration, varicocele grade, laterality, follicle-stimulating hormone, testicular volume and testicular histology. RESULTS: The study included 31 men with a mean ± SD age of 34.9 ± 8.7 years and mean followup of 19.3 ± 3.3 months. Hypospermatogenesis, late maturation arrest, early maturation arrest and Sertoli-cell-only were observed in 13, 6, 2 and 10 patients, respectively. Overall, sperm recovery was evident in 10 of 31 (32.3%) patients (persistent recovery 19.4%, intermittent recovery 6.5%, relapse 6.5%). Sperm were recovered in patients with hypospermatogenesis (7 of 13, 53.8%) and late maturation arrest (3 of 6, 50%). No sperm were recovered in those with early maturation arrest or Sertoli-cell-only. Among the variables only histological patterns demonstrated a significant correlation with recovery (rho = 0.504, p = 0.004). None of variables was significantly correlated with relapse. Bilateral varicocele repair demonstrated a strong yet nonsignificant negative correlation with relapse (rho = -0.612, p = 0.06). CONCLUSIONS: Varicocelectomy could recover motile sperm in men with nonobstructive azoospermia, palpable varicoceles and hypospermatogenesis or late maturation arrest. No sperm was recovered with early maturation arrest or Sertoli-cell-only. Recovery might be persistent or intermittent, or involve relapse of azoospermia. Testicular histology was the sole parameter significantly correlated with recovery and no predictors of relapse could be identified. This prognostic role of testicular biopsy is imperative in couple counseling.

Does varicocele repair improve male infertility? An evidence-based perspective from a randomized, controlled trial.

BACKGROUND: Randomized controlled trials (RCTs) addressing varicocele treatment are scarce and have conflicting outcomes. OBJECTIVE: To determine whether varicocele treatment is superior or inferior to no treatment in male infertility from an evidence-based perspective. DESIGN, SETTING, AND PARTICIPANTS: A prospective, nonmasked, parallel-group RCT with a one-to-one concealed-to-random allocation was conducted at the authors' institution from February 2006 to October 2009. Married men 20-39 yr of age who had experience infertility ≥1 yr, had palpable varicoceles, and with at least one impaired semen parameter (sperm concentration <20 million/ml, progressive motility <50%, or normal morphology <30%) were eligible. Exclusions included subclinical or recurrent varicoceles, normal semen parameters, and azoospermia. Sample size analysis suggested 68 participants per arm. INTERVENTION: Participants were randomly allocated to observation (the control arm [CA]) or subinguinal microsurgical varicocelectomy (the treatment arm [TA]). Semen analyses were obtained at baseline (three analyses) and at follow-up months 3, 6, 9, and 12. The mean of each sperm parameter at baseline and follow-ups was determined. MEASUREMENTS: We measured the spontaneous pregnancy rate (the primary outcome), changes from baseline in mean semen parameters, and the occurrence of adverse events (AE-the secondary outcomes) during 12-mo follow-up; p<0.05 was considered significant. RESULTS AND LIMITATIONS: Analysis included 145 participants (CA: n=72; TA: n=73), with a mean age plus or minus standard deviation of 29.3±5.7 in the CA and 28.4±5.7 in the TA (p=0.34). Baseline characteristics in both arms were comparable. Spontaneous pregnancy was achieved in 13.9% (CA) versus 32.9% (TA), with an odds ratio (OR) of 3.04 (95% confidence interval [CI], 1.33-6.95) and a number needed to treat (NNT) of 5.27 patients (95% CI, 1.55-8.99). In CA within-arm analysis, none of semen parameters revealed significant changes from baseline (sperm concentration [p=0.18], progressive motility [p=0.29], and normal morphology [p=0.05]). Conversely, in TA within-arm analysis, the mean of all semen parameters improved significantly in follow-up versus baseline (p<0.0001). In between-arm analysis, all semen parameters improved significantly in the TA versus CA (p<0.0001). No AEs were reported. CONCLUSIONS: Our RCT provided level 1b evidence of the superiority of varicocelectomy over observation in infertile men with palpable varicoceles and impaired semen quality, with increased odds of spontaneous pregnancy and improvements in semen characteristics within 1-yr of follow-up.

Botulinum toxin-A injections into neurogenic overactive bladder--to include or exclude the trigone? A prospective, randomized, controlled trial.

PURPOSE: The short-term outcomes of initial detrusor injections vs combined detrusor-trigone botulinum toxin-A injections were determined in patients with spinal cord injury-neurogenic detrusor overactivity. MATERIALS AND METHODS: Adults with refractory spinal cord injury-neurogenic detrusor overactivity who strictly discontinued anticholinergics were recruited for the study. At a 1:1 ratio patients randomly received 300 U botulinum toxin-A intradetrusor injections excluding the trigone (detrusor arm) or 200 U intradetrusor plus 100 U intratrigonal injections (combined arm). Study end points were determination of the impact on incontinence episodes, complete dryness, quality of life, reusing anticholinergics, maximum detrusor pressure, reflex volume, maximum cystometric capacity, vesicoureteral reflux and adverse events. Patients were evaluated at baseline, and 2, 8, 12 and 18 weeks after injection. Statistical significance was considered at p<0.05. RESULTS: Analysis included 18 patients per arm with no significant baseline differences. On within group analysis all parameters improved significantly compared to baseline. On between group analysis in the detrusor vs the combined arm at week 8 incontinence decreased by 52.4% vs 80.9% (number needed to treat 1.91 vs 1.23 patients, p<0.001), complete dryness was achieved in 33.3% vs 66.7% of patients (number needed to treat 3 vs 1.5, p<0.001) and quality of life score was decreased by 46.76% vs 48.13% (number needed to treat 2.14 vs 2.08, p<0.44). The absolute difference was 60% vs 82.5% for reflex volume (p<0.001), 66.2% vs 68.4% for maximum cystometric capacity (p<0.22) and -42.3% vs -41.9% for maximum detrusor pressure (p<0.21). At week 18 anticholinergics were needed again in 9 (50%) and 4 patients (22.2%) patients, respectively. No patient showed new or upgraded vesicoureteral reflux or reported significant adverse events. CONCLUSIONS: In the short term all parameters improved significantly in each arm. The superiority of including rather than excluding the trigone was significant.

Tamsulosin to treat uncomplicated distal ureteral calculi: a double blind randomized placebo-controlled trial.

PURPOSE: To evaluate efficacy and outcome of tamsulosin therapy for 4 mm-10 mm uncomplicated distal ureteral stones. MATERIALS AND METHODS: A total of 150 patients (adults with newly diagnosed single unilateral distal ureteral 4 mm-10 mm stones) were double blindly randomized into GA or GB. All patients received traditional treatment of hydration and analgesia as needed. Additionally, patients received either placebo (GA) or 0.4 mg tamsulosin (GB) oral tablets once daily. Treatment and follow up were continued for up to 4 weeks. Endpoints were spontaneous stone passage rates (SPR) and passage time for different stone sizes within 4 weeks study period. RESULTS: Analysis included 75 patients, in each group, with comparable characteristics. Overall SPR was 56% in GA and 81.3% in GB; achieving significant absolute risk reduction (ARR = 25.3%; p < 0.01) and number needed to treat (NNT) of 3.95. SPR for stones

The clinicopathologic patterns of prostatic diseases and prostate cancer in Saudi patients.

OBJECTIVE: To determine the clinicopathologic patterns of prostatic diseases in Saudi patients, with special emphasis on prostate cancer (PCa). METHODS: The records of patients who underwent histopathological examinations of their prostatic specimens in King Abdulaziz University Medical City and King Faisal Specialist Hospital, Jeddah, Kingdom of Saudi Arabia, between June 2003 and June 2008 were reviewed retrospectively. The age, indications for biopsy, histological diagnosis, and Gleason grading of cancer patients, were studied. RESULTS: The study included 330 patients aged 37-100 years (median=68). Specimens included 233 transrectal ultrasound (TRUS) biopsies, 85 transurethral resection of the prostate (TURP), 8 simple prostatectomies, 3 radical prostatectomies, and one radical cystoprostatectomy. Indications for TRUS guided biopsy in PCa patients were elevated prostate specific antigen (PSA) (85.2%), abnormal digital rectal examination (5.5%) or both (9.3%). Prostate specific antigen values <4 ng/ml were found in 13.6% of PCa patients. Among others, adenocarcinoma was found in 28.5%, benign prostatic hyperplasia (BPH) alone in 43.3%, BPH with inflammation in 20.3% and inflammation alone in 4.2%. In specimens of TURP or simple prostatectomy for apparently benign disease, incidental PCa was detected in 14/93 (15%). The Gleason sum of > or = 6 was found in 92.8% of patients. CONCLUSION: The incidence of prostate cancer in Saudi Arabia is low compared to the western countries. However, incidental PCa detected in presumed benign disease appears to be rising. Further future studies addressing this issue are needed to confirm the potential rising trend, and its possible etiology. Our findings support the recommendations to lower the PSA cutoff value for prostatic biopsy to 2.5 rather than 4 ng/ml.

Prostate inflammation. Association with benign prostatic hyperplasia and prostate cancer.

OBJECTIVE: To study the association and possible relationship of prostate inflammation with benign prostatic hyperplasia (BPH), and prostate cancer. METHODS: The medical records and pathological findings of all Saudi patients who underwent transrectal ultrasound guided prostatic needle biopsies in King Abdulaziz University Medical City, Jeddah,Kingdom of Saudi Arabia from June 2003 to June 2008 were reviewed retrospectively. The indications for biopsy were elevated levels of serum prostate specific antigen, abnormal findings on digital rectal examination, or both. The specimens harboring inflammation, adenocarcinoma, BPH, or their combinations, were selected and included in the study. RESULTS: A total of 214 patients were selected with an age ranging from 37-100 years (median=68). Inflammation was histologically evident in 88 patients. Of them, only one demonstrated acute inflammation, while 87/88 demonstrated chronic inflammation with, or without acute inflammation. Histopathologic features were categorized into 3 main categories: inflammation alone (12/214, 5.6%), BPH category (126/214, 58.9%), and cancer category (76/214, 35.5%) patients. The last 2 categories also included cases associated with inflammation. In the overall analysis of 214 specimens, BPH with inflammation was more prevalent than cancer with inflammation (43/214 [20.1%] versus 33/214 [15.4%]). In a subgroup analysis within each category, inflammation was less prevalent in the BPH category compared to the cancer category (43/126 [34.1%] versus 33/76 [43.4%]). CONCLUSION: The association between chronic inflammation and both BPH and cancer is obvious in our study. Further studies are needed to substantiate this observation, and to clarify the magnitude of association of inflammation with BPH compared to cancer.