PRSS8, encoding prostasin, is mutated in patients with autosomal recessive ichthyosis.

Ichthyosis is a genetically heterogeneous genodermatosis characterized by severely rough, dry and scaly skin. We report two consanguineous families with congenital ichthyosis. Combined positional mapping and exome sequencing of the two families revealed novel homozygous likely deleterious variants in PRSS8 (encoding prostasin) within a linkage locus on chromosome 16. One variant involved a canonical splice site and was associated with reduced abundance of the normal transcript, while the other was a missense variant that altered a highly conserved residue. The phenotype of Prss8 knockout mouse bears a striking resemblance to the one we describe in human patients, including the skin histopathology. Our data suggest a novel PRSS8-related ichthyosis disorder.

A genomics approach to male infertility.

PURPOSE: Male infertility remains poorly understood at the molecular level. We aimed in this study to investigate the yield of a "genomics first" approach to male infertility. METHODS: Patients with severe oligospermia and nonobstructive azoospermia were investigated using exome sequencing (ES) in parallel with the standard practice of chromosomal analysis. RESULTS: In 285 patients, 10.5% (n = 30) had evidence of chromosomal aberrations while nearly a quarter (n = 69; 24.2%) had a potential monogenic form of male infertility. The latter ranged from variants in genes previously reported to cause male infertility with or without other phenotypes in humans (24 patients; 8.4%) to those in novel candidate genes reported in this study (37 patients; 12.9%). The 33 candidate genes have biological links to male germ cell development including compatible mouse knockouts, and a few (TERB1 [CCDC79], PIWIL2, MAGEE2, and ZSWIM7) were found to be independently mutated in unrelated patients in our cohort. We also found that male infertility can be the sole or major phenotypic expression of a number of genes that are known to cause multisystemic manifestations in humans (n = 9 patients; 3.1%). CONCLUSION: The standard approach to male infertility overlooks the significant contribution of monogenic causes to this important clinical entity.

Comparison of sperm retrieval rate between superficial and deep dissection during microscopic testicular sperm extraction.

Objective: The purpose of the study was to compare the outcome of microscopic testicular sperm extraction (micro-TESE) between superficial and deep dissection on the same testicle in terms of sperm retrieval rate (SRR). Patients and Methods: In a retrospective study from June 2019 to October 2021, 44 patients with nonobstructive azoospermia who underwent micro-TESE with positive results (mature sperm identified) were included. Eight patients were excluded from the study due to deficient documentation on superficial and deep dissection. A total of 36 patients were included; 60 testicles were examined for superficial and deep biopsies. Testicular histopathology was performed in all patients, and a hormonal evaluation was obtained before the micro-TESE attempt. Results: Thirty-six patients and 60 testicles were included in the study. Of them, 47 (78.3%) testicles had positive results. Superficial TESE was positive in 38 (63.3%) testicles, and deep TESE was successful in 45 (75.0%) testicles. An improvement of 13.9% in the SRR was observed, following deep dissection. However, there was no statistically significant difference (P = 0.166). Rates of positive sperm retrieval (from any side) did not differ significantly based on patients' age, microdissection testicular sperm extraction sides, and hormonal concentrations; these differences were not apparent after superficial or deep TESE. Conclusion: The presented findings suggest that although successful SRRs of deep TESE were higher than that of its superficial counterpart, there was no significant statistical difference. A larger body of evidence is needed to provide a higher grade of recommendation.

Global Practice Patterns in the Evaluation of Non-Obstructive Azoospermia: Results of a World-Wide Survey and Expert Recommendations.

PURPOSE: Non-obstructive azoospermia (NOA) represents the persistent absence of sperm in ejaculate without obstruction, stemming from diverse disease processes. This survey explores global practices in NOA diagnosis, comparing them with guidelines and offering expert recommendations. MATERIALS AND METHODS: A 56-item questionnaire survey on NOA diagnosis and management was conducted globally from July to September 2022. This paper focuses on part 1, evaluating NOA diagnosis. Data from 367 participants across 49 countries were analyzed descriptively, with a Delphi process used for expert recommendations. RESULTS: Of 336 eligible responses, most participants were experienced attending physicians (70.93%). To diagnose azoospermia definitively, 81.7% requested two semen samples. Commonly ordered hormone tests included serum follicle-stimulating hormone (FSH) (97.0%), total testosterone (92.9%), and luteinizing hormone (86.9%). Genetic testing was requested by 66.6%, with karyotype analysis (86.2%) and Y chromosome microdeletions (88.3%) prevalent. Diagnostic testicular biopsy, distinguishing obstructive azoospermia (OA) from NOA, was not performed by 45.1%, while 34.6% did it selectively. Differentiation relied on physical examination (76.1%), serum hormone profiles (69.6%), and semen tests (68.1%). Expectations of finding sperm surgically were higher in men with normal FSH, larger testes, and a history of sperm in ejaculate. CONCLUSIONS: This expert survey, encompassing 367 participants from 49 countries, unveils congruence with recommended guidelines in NOA diagnosis. However, noteworthy disparities in practices suggest a need for evidence-based, international consensus guidelines to standardize NOA evaluation, addressing existing gaps in professional recommendations.

Global Practice Patterns and Variations in the Medical and Surgical Management of Non-Obstructive Azoospermia: Results of a World-Wide Survey, Guidelines and Expert Recommendations.

PURPOSE: Non-obstructive azoospermia (NOA) is a common, but complex problem, with multiple therapeutic options and a lack of clear guidelines. Hence, there is considerable controversy and marked variation in the management of NOA. This survey evaluates contemporary global practices related to medical and surgical management for patients with NOA. MATERIALS AND METHODS: A 56-question online survey covering various aspects of the evaluation and management of NOA was sent to specialists around the globe. This paper analyzes the results of the second half of the survey dealing with the management of NOA. Results have been compared to current guidelines, and expert recommendations have been provided using a Delphi process. RESULTS: Participants from 49 countries submitted 336 valid responses. Hormonal therapy for 3 to 6 months was suggested before surgical sperm retrieval (SSR) by 29.6% and 23.6% of participants for normogonadotropic hypogonadism and hypergonadotropic hypogonadism respectively. The SSR rate was reported as 50.0% by 26.0% to 50.0% of participants. Interestingly, 46.0% reported successful SSR in <10% of men with Klinefelter syndrome and 41.3% routinely recommended preimplantation genetic testing. Varicocele repair prior to SSR is recommended by 57.7%. Half of the respondents (57.4%) reported using ultrasound to identify the most vascularized areas in the testis for SSR. One-third proceed directly to microdissection testicular sperm extraction (mTESE) in every case of NOA while others use a staged approach. After a failed conventional TESE, 23.8% wait for 3 months, while 33.1% wait for 6 months before proceeding to mTESE. The cut-off of follicle-stimulating hormone for positive SSR was reported to be 12-19 IU/mL by 22.5% of participants and 20-40 IU/mL by 27.8%, while 31.8% reported no upper limit. CONCLUSIONS: This is the largest survey to date on the real-world medical and surgical management of NOA by reproductive experts. It demonstrates a diverse practice pattern and highlights the need for evidence-based international consensus guidelines.

Influence of microsurgical varicocelectomy on human sperm mitochondrial DNA copy number: a pilot study.

BACKGROUND: There is good evidence to show that varicocele repair can improve conventional sperm parameters, as well as, sperm DNA integrity, in infertile men with a clinical varicocele. OBJECTIVE: To examine the effect of varicocelectomy on sperm quality, specifically, sperm nuclear chromatin integrity and sperm mitochondrial DNA (mtDNA) copy number. DESIGN, SETTING, AND PARTICIPANTS: A prospective study done between March 2007 and January 2008. We evaluated a consecutive series of infertile men (n = 14) presenting to Ovo clinic with one year or more history of infertility, a clinically palpable varicocele and poor motility (<25 % rapid progressive and <50 % progressive). SURGICAL PROCEDURE: Microsurgical sub-inguinal varicocelectomy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Conventional sperm parameters, sperm mtDNA copy number (by real time PCR) and sperm chromatin structure assay (SCSA) parameters (%DFI,% HDS) before and 4 months after microsurgical varicocelectomy. RESULTS AND LIMITATIONS: Sperm concentration and SCSA parameters (%DFI and %HDS) improved significantly after surgery (P < 0.05). Sperm mitochondrial DNA copy number decreased significantly after surgery (27 ± 30 to 9 ± 6 copies per sperm, respectively, P = 0.032). There was a significant negative correlation between mitochondrial DNA copy number and sperm motility (r = - 0.71, P = 0.002). CONCLUSION: These findings support the concept that correction of a varicocele can improve spermatogenesis and sperm function, as mitochondrial DNA copy number has been suggested to reflect the efficiency of spermatogenesis and has been inversely related to sperm motility.

Fulminant corporal infection induced by Fournier gangrene: A case report with unusual presentation.

Fournier gangrene is a life-threatening surgical emergency caused by multiple infectious organism usually affecting the subcutaneous perineal, genital or perianal region with high incidence in immunocompromised patients. In very rare situations such our case when it involves the Deep perineal fascia and invading into the corporal body, the necrotizing tissue spread and control becomes more challenging and lead into devastating events with high mortality rate. Staged timely debridement with highly daily examination to rule out necrosis spread is highly recommended.

Spontaneous pregnancy post orchidopexy of bilateral retractile testes in an adult: A case report.

Retractile testes have been associated with male factor infertility. However, whether surgical correction is indicated in those males is unknown. Herein, we report a case of a 37 year old male with primary infertile for 7 years with no apparent cause other than retractile testes. Bilateral orchidopexy was done and his wife achieved spontaneous pregnancy and delivery of a healthy girl.

Bilateral persistent sinus tracts formation post bilateral microsurgical inguinal varicocelectomy: A case report.

Varicocele is a common case encountered in urology practice accounting for 15-20% of the general population. We are reporting a rare case of infected inguinal wounds post bilateral microsurgical varicocelectomy which led to persistent bilateral wound sinus formation. After multiple bedside wound debridement and sinus tract excision in operation theater, the patient's wounds were healed. We advise managing post-operative subcutaneous collections very closely to avoid such complications. When it happens and wound debridement is planned, we advise not to leave any dead space behind via using fat flaps.

Efficacy of follicle-stimulating hormone as a treatment of severe idiopathic oligospermia: A retrospective study.

INTRODUCTION: About 15% of couples are infertile, with the male factor being responsible for about 50% of these cases of infertility. Idiopathic oligospermia (IO) is a dilemma that faces every andrologist and yet is one of the most common causes of male infertility. Although studies have shed some light on multiple treatment modalities and their effectiveness, one of the most fascinating ones is follicle-stimulating hormone (FSH). METHODOLOGY: This is a single tertiary center retrospective study; all patients with severe IO (sperm count of <5 million/ml) from January 2016 till January 2018 were included in the study. We divided our retrospective population into 2 groups, Group 1 who received FSH 75 IU (Menogon®) twice a week and Group 2 who received FSH 150 IU (Menogon®) twice a week. Semen parameters were recorded pretreatment and posttreatment. RESULTS: Number of the patients included in the study was 32. Group 1 included 16 patients who received FSH 75 IU. Group 2 included 16 patients who received FSH 150 IU. After 4 months of treatment, the mean sperm count in Group 1 increased to 4.745 million/ml (pretreatment was 1.235 million/ml), while in Group 2, it was 1.516 million/ml (pretreatment was 0.578 million/ml). The mean total motility in Group 1 was 20.3%, while Group 2 mean total motility was 27.5%. CONCLUSION: In conclusion, our study elicited that a dose of FSH as low as 75 IU can improve sperm count significantly in patients with severe IO.

Infertility secondary to an infected hydrocele: A case report.

Hydroceles are one of the most common causes of scrotal swelling affecting around 1% of the adult population. While hydroceles are usually asymptomatic, some hydroceles can lead to infertility. We will present a case of a 34-year-old man who was referred to our center as a case of primary infertility (sever oligospermia 1.1 million/ml) for 4 years and was found to have bilateral hydroceles (infected right hydrocele). At 18 months post bilateral hydrocelectomy, the patient's total sperm count improved to 43 Million/ml. Therefore, we highly recommend considering hydrocele as an etiology in any patient with idiopathic infertility.

Splenogonadal fusion: A rare case report and literature review.

Splenogonadal fusion is a rare benign congenital anomaly with few cases described in the literature. It is 16 times more common in males than in females. A 22 year-old healthy male with cryptorchidism presented with preoperative imaging strongly suggestive of malignancy. Histopathology after left orchiectomy showed mixed splenic and testicular tissue with no sign of malignancy. Splenogonadal fusion is rarely diagnosed preoperatively. It should be included in differential diagnoses in patients presenting with a testicular or abdominal mass. Greater recognition of this rare anomaly may facilitate testis sparing surgery in future cases.

Intra-scrotal extra-testicular schwannoma: A case report and literature review.

Intra-scrotal schwannoma is a rare neoplasm and a few reports were describing this entity in the literature and mostly difficult to be diagnosed pre operatively(1) We recently treated a case of intra-scrotal extra-testicular schwannoma which was discovered in a patient with history of painless scrotal lesion for 5 years. paratesticular lesion excision was done which was result as schwannoma tissue. follow up with US scrotum was unremarkable for the patient. surgical excision will provide diagnostic and therapeutic goals. Even tough recurrence is rare a urologist should take care to ensure complete surgical resection.

A 3-piece penile prosthesis salvage in the presence of late-onset infected hematoma: Clinical, radiological and intraoperative findings-A case report.

INTRODUCTION: Erectile dysfunction (ED) is a common health problem affecting 30% of young men worldwide. Despite the availability of non-invasive lines of management, penile prosthesis insertion is considered as a definite solution for ED. Despite strict perioperative measures, infection still complicates around 3% of penile prosthesis surgeries. PRESENTATION OF CASE: This is a case of a 36-year-old male who had an infected scrotal hematoma that led to prosthesis malfunction due to the inability to locate the pump to activate and deactivate the device. Intraoperatively, the prosthesis was salvaged after hematoma evacuation and ensuring a good device functionality. DISCUSSION AND CONCLUSION: Infected penile prostheses are usually either removed completely with a new device insertion a few months later or exchanged at the same setting with vigorous wound washout. We suggest salvaging penile implants which are surrounded by infected hematomas in selected patients who don't manifest systemic signs of infection. This approach will help in cost reduction and avoiding further intraoperative complications.

Perioperative predictors for post-prostatectomy urinary incontinence in prostate cancer patients following robotic-assisted radical prostatectomy: Long-term results of a Canadian prospective cohort.

INTRODUCTION: We aimed to report the impact of perioperative factors that have not been well-studied on continence recovery following robotic-assisted radical prostatectomy (RARP). METHODS: We analyzed data of 322 men with localized prostate cancer who underwent RARP between October 2006 and May 2015 in a single Canadian centre. All patients were assessed at one, three, six, 12, and 24 months after surgery. We evaluated risk factors for post-prostatectomy urinary incontinence from a prospectively collected database in multivariate Cox regression analysis. The primary endpoint was continence, defined as 0 pad usage per day. RESULTS: 0-pad continence rates were 126/322 (39%), 187/321 (58%), 222/312 (71%), 238/294 (80%), and 233/257 (91%) at one, three, six, 12, and 24 months, respectively. Bladder neck preservation (hazard ratio [HR] 0.71; 95% confidence interval [CI] 0.5-0.99; p=0.04), and prostate size (HR 0.99; 95% CI 0.98-0.99; p=0.02) were independent predictors of continence recovery after RARP. Smoking at time of surgery predicted delayed continence recovery on multivariate analysis (HR 1.42; 95% CI 1.01-1.99; p=0.04). Neurovascular bundles preservation was associated with continence recovery after 24 months. No statistically significant correlation was found with other variables, such as age, body mass index, Charlson comorbidity index, preoperative oncological baseline parameters, presence of median lobe, or thermal energy use. CONCLUSIONS: Our results confirmed known predictors of postprostatectomy incontinence (PPI), namely bladder neck resection and large prostate volume. Noteworthy, cigarette smoking at the time of RARP was found to be a possible independent risk factor for PPI. This study is hypothesis-generating.

Microdissection testicular sperm extraction: Overall results and impact of preoperative testosterone level on sperm retrieval rate in patients with nonobstructive azoospermia.

OBJECTIVE: The main objective is to review the overall result and impact of preoperative testosterone level on sperm retrieval rate (SRR) by microdissection testicular sperm extraction (micro-TESE) in patients with nonobstructive azoospermia (NOA). MATERIALS AND METHODS: We retrospectively reviewed the files of patients who underwent micro-TESE for NOA from August 2013 to December 2014. All patients were evaluated with history, physical examination, and hormonal assessment. Patients who had previous micro-TESE, obstructive azoospermia, or who took hormone therapy were excluded from the study. Patients were classified into two groups. Group A included patients who had low testosterone (<10 nmol/L), and Group B included patients with normal testosterone (>10 nmol/L). The primary endpoint was to review the overall results of the procedure and the impact of preoperative testosterone level on sperm retrieval. RESULTS: A total of 264 patients with NOA underwent micro-TESE. Group A included 133 patients with low testosterone (<10 nmol/l) with a median age of 36 ± 6.59 years, and Group B included 131 patients with normal testosterone (>10 nmol/L) with a median age of 33 ± 7.88 years (P = 0.1350). There was no significant difference in follicle-stimulating hormone (P = 0.2467), luteinizing hormone (P = 0.1078), prolactin (P = 0.5619), and testicular volume (P = 0.4052), whereas a significant difference was found in testosterone level (P = 0.0001) in both groups. Overall, sperm were successfully retrieved in 48.8% of men. SRR in Group B was significantly higher (57.25%) than that in Group A (40.60%) (P = 0.0068). SRR in patients with Sertoli-cell-only pathology was 30.35%, hypospermatogenesis was 89.74%, and maturation arrest was 32.43%. CONCLUSION: Micro-TESE is a successful and safe procedure in NOA patients with a poor prognosis. Preoperative testosterone level has a significant impact in the SRR by micro-TESE.

Scrotal Abscess Precipitating Late Infection of a Malleable Penile Prosthesis: The Risk Never Evanesces.

Although infrequent, infections represent the dreadful complication of penile prosthesis implantation. The incidence substantially decreases after a few infection-free postoperative months. We report herein a case of a very late penile prosthesis infection from a fistualizing scrotal abscess in a 67-year-old man. The patient presented with a one-month history of persistent penile-base discharge from a right hemiscrotal swelling. On examination, mild penile tenderness and a discharging penoscrotal-junction sinus were noted. Microbiological wound culture was positive for Staphylococcus epidermidis. Magnetic resonance imaging revealed this multiloculated fluid collection's communication with the right corporal body. Removal of the prosthesis was performed. Pathological evaluation of the dissected fistula was suggestive of acute on top of chronic inflammatory reactions. To our knowledge, this is the first report of a scrotal abscess leading to penile prosthesis infection 15 years after an uneventful implantation.

Feasibility of planned mini-laparotomy and adhesiolysis at the time of robotic-assisted radical prostatectomy in patients with prior major abdominal surgery.

INTRODUCTION: Our aim was to report our experience on the feasibility of completing radical prostatectomy robotically after planned open adhesiolysis for prior major abdominal surgery with previous midline laparotomy scar. METHODS: We searched our prospectively collected database of robotic assisted-radical prostatectomy (RARP) performed between October 2006 and October 2012 by a single fellowship-trained surgeon to identify all patients who underwent planned initial mini-laparotomy for release of abdominal adhesions at time of RARP. Among 250 RARP patients, five patients fulfilled these criteria. RESULTS: All patients had prostatectomy completed robotically. The mean values of patients' demographics were as follows: Age 61.8 years (range 54-69), body mass index 30.7 (range 24.3-45.3), and prostate volume 41.5 ml (range 30.8-54). Mean operative time was 245 min (range 190-280) and estimated blood loss 410 ml (range 300-650). Median hospital stay was one day (range 1-7). Postoperatively, there was one prolonged ileus, which resolved spontaneously, and one myocardial infarction. CONCLUSIONS: Robotic completion of radical prostatectomy after open adhesiolysis is feasible. This approach maintains most minimally invasive advantages of RARP, despite a slightly longer hospital stay. In the best interest of patients, robotic surgeons are encouraged to finish the case robotically rather than attempting an open approach.

Predictors of early continence following robot-assisted radical prostatectomy.

INTRODUCTION: Functional outcomes after robot-assisted radical prostatectomy (RARP) greatly influence patient quality of life. Data regarding predictors of early continence, especially 1 month following RARP, are limited. Previous reports mainly address immediate or 3-month postoperative continence rates. We examine preoperative predictors of pad-free continence recovery at the first follow-up visit 1 month after RARP. METHODS: Between January 2007 and January 2013, preoperative and follow-up data were prospectively collected for 327 RARP patients operated on by 2 fellowship-trained surgeons (AEH and KCZ). Patient and operative characteristics included age, body mass index (BMI), staging, preoperative prostate-specific antigen (PSA), prostate weight, International Prostate Symptom Score (IPSS), Sexual Health Inventory for Men (SHIM) score and type of nerve-sparing performed. Continence was defined by 0-pad usage at 1 month follow-up. Univariate and multivariate logistic regression models were used to assess for predictors of early continence. RESULTS: Overall, 44% of patients were pad-free 1 month post-RARP. In multivariate regression analysis, age (odds ratio [OR] 0.946, confidence interval [CI] 95%: 0.91, 0.98) and IPSS (OR: 0.953, CI 95%: 0.92, 0.99) were independent predictors of urinary continence 1 month following RARP. Other variables (BMI, staging, preoperative PSA, SHIM score, prostate weight and type of nerve-sparing) were not statistically significant predictors of early continence. Limitations of this study include missing data for comorbidities, patient use of pelvic floor exercises and patient maximal activity. Moreover, patient-reported continence using a 0-pad usage definition represents a semiquantitative and subjective measurement. CONCLUSION: In a broad population of patients who underwent RARP at our institution, 44% of patients were pad-free at 1 month. Age and IPSS were independent predictors of early continence after surgery. Men of advanced age and those with significant lower urinary tract symptoms prior to RARP should be counselled on the increased risk of urinary incontinence in the early stages.

Oncological and functional outcomes of 722 robot-assisted radical prostatectomy (RARP) cases: The largest Canadian 5-year experience.

INTRODUCTION: While RARP (robotic-assisted radical prostatectomy) has become the predominant surgical approach to treat localized prostate cancer, there is little Canadian data on its oncological and functional outcomes. We describe the largest RARP experience in Canada. METHODS: Data from 722 patients who underwent RARP performed by 7 surgeons (AEH performed 288, TH 69, JBL 23, SB 17, HW 15, QT 7, and KCZ 303 patients) were collected prospectively from October 2006 to December 2013. Preoperative characteristics, as well as postoperative surgical and pathological outcomes, were collected. Functional and oncological outcomes were also assessed up to 72 months postoperative. RESULTS: The median follow-up (Q1-Q3) was 18 months (9-36). The D'Amico risk stratification distribution was 31% low, 58% intermediate and 11% high-risk. The median operative time was 178 minutes (142-205), blood loss was 200 mL (150-300) and the postoperative hospital stay was 1 day (1-23). The transfusion rate was only 1.0%. There were 0.7% major (Clavien III-IV) and 10.1% minor (Clavien I-II) postoperative complications, with no mortality. Pathologically, 445 men (70%) were stage pT2, of which 81 (18%) had a positive surgical margin (PSM). In addition, 189 patients (30%) were stage pT3 and 87 (46%) with PSM. Urinary continence (0-pads/day) returned at 3, 6, and 12 months for 68%, 80%, and 90% of patients, respectively. Overall, the potency rates (successful penetration) for all men at 6, 12, and 24 months were 37%, 52%, and 59%, respectively. Biochemical recurrence was observed in 28 patients (4.9%), and 14 patients (2.4%) were referred for early salvage radiotherapy. In total, 49 patients (8.4%) underwent radio-therapy and/or hormonal therapy. CONCLUSIONS: This study shows similar results compared to other high-volume RARP programs. Being the largest RARP experience in Canada, we report that RARP is safe with acceptable oncologic outcomes in a Canadian setting.