Voiding and renal function 10 years after radical cystectomy and orthotopic neobladder in women.

OBJECTIVES: To assess long-term voiding and renal function (RF) changes after radical cystectomy (RC) and orthotopic neobladder (ONB) surgery in women without disease recurrence. MATERIAL AND METHODS: Women who underwent RC and ONB reconstruction between 1995 and 2011 were included in this study. Patients who developed disease failure or were lost to follow-up were excluded. The study outcomes were long-term voiding function and the incidence and predictors of RF deterioration (defined as >20% decline of baseline). Analysis was performed using the log-rank test and Cox regression analysis. RESULTS: The study included 195 patients with a median (interquartile range) follow-up of 98 (53-151) months, of whom 95 had >10 years of follow-up. Daytime continence, night-time continence and chronic urine retention (CUR) were identified in 170 (87%), 134 (69%) and 52 patients (27%), respectively. Among patients with >10 years of follow-up, 82 (86%), 66 (70%) and 31 (33%) had daytime continence, night-time continence and CUR at the last follow-up visit, respectively. RF deterioration events occurred in 74 patients throughout the follow-up and chronic kidney disease (CKD) stage III-V developed in 80 patients. Patients' age (hazard ratio [HR] 1.41, 95% confidence interval [CI]1.06-1.89; P = 0.02) and serous-lined extramural tunnel diversion (HR 0.43, 95% CI 0.19-0.86; P = 0.02) were the independent predictors of RF deterioration. Among patients with >10 years of follow-up, RF deteriorated in 46 patients (49%) and CKD stage III-V developed in 40 (42%). CONCLUSION: Women surviving more than 10 years after RC and ONB maintained acceptable continence status, apart from having a higher CUR rate, compared to those followed for <10 years. However, RF deterioration developed in nearly half of them.

The short-term effects of tolterodine on nocturnal incontinence after ileal orthotopic neobladder: a randomised crossover placebo-controlled study.

OBJECTIVES: To assess the effect of tolterodine in the treatment of nocturnal urinary incontinence (NUI) after ileal orthotopic neobladder (ONB). PATIENTS AND METHODS: This is a prospective randomised placebo-controlled crossover study (clinicaltrials.gov: NCT02877901). Patients with NUI after ONB were randomly allocated into two equal groups. Group T received 4 mg extended-release tolterodine at bed-time and Group P received placebo for 4 weeks followed by 2 weeks of washout, then crossed over to the alternate therapy for 4 weeks. Patients were assessed by the number of pads used per night (PPN) and with the Arabic version of the International Consultation on Incontinence Modular Questionnaire-Short Form (ICIQ-SF) at both phases of the study. The outcomes were the rate of NUI improvement and medication adverse events. RESULTS: Out of 172 patients, 150 and 122 patients were evaluated at both phases of the study. The mean ICIQ-SF scores and PPN were significantly decreased in Group T compared to Group P in both study phases (P < 0.001). In Group T, 15 (10%) and 11 (9%) patients became dry after the first allocation and crossover, respectively. In Group T, 60 (77.9%) patients reported improvement vs four (5.5%) in Group P (P < 0.001) after the first allocation. Similarly, 46 (73%) and seven (11.9%) patients showed improvement in groups T and P after the crossover, respectively (P < 0.001). Dry mouth occurred in 31 (20.8%) patients. CONCLUSIONS: Tolterodine seems to be a good choice for treatment of NUI after radical cystectomy and ONB. However, further studies are needed to delineate the long-term effects and the associated urodynamic characteristics.

Acute kidney injury following radical cystectomy and urinary diversion: predictors and associated morbidity.

INTRODUCTION: Acute kidney injury (AKI) after major surgeries is associated with significant morbidity and mortality. We aim to report incidence, predictors and associated comorbidities of AKI after radical cystectomy in a large cohort of patients. MATERIALS AND METHODS: We conducted a retrospective analysis of 1000 patients who underwent open radical cystectomy in a tertiary referral center. Perioperative serum creatinine measurements were used to define AKI according to the RIFLE criteria (as Risk, Injury and Failure). The predictors of AKI after surgery were determined using univariate and multivariate analyses. RESULTS: Out of 988 evaluable patients, AKI developed in 46 (4.7%). According to RIFLE criteria; AKI-Risk, AKI-Injury and AKI-Failure occurred in 26 (2.6%), 9 (0.9%) and 11 (1.1%) patients, respectively. Multivariate analysis showed that performing nephroureterectomy with cystectomy (Odds ratio [OR]: 4.3; 95% Confidence interval [CI]: 1.3-13.6; p=0.01) and the development of high grade complications (OR: 3.8; 95% CI 1.9-7.2; p<0.0001) were independently associated with AKI. CONCLUSIONS: AKI is a significant morbidity after radical cystectomy and the term should be included during routine cystectomy morbidity assessment.

Residual stones after percutaneous nephrolithotomy: comparison of intraoperative assessment and postoperative non-contrast computerized tomography.

OBJECTIVES: To compare the intraoperative surgeon perspective for detection of residual fragments (RFs) after percutaneous nephrolithotomy (PNL) with postoperative NCCT. METHODS: A prospective study of adult patients who underwent PNL between March and September 2014 was conducted. Stone complexity was evaluated using the Guy's stone score (GSS). All patients were evaluated by pre- and postoperative NCCT. After the procedure, the surgeon had been asked whether there were residual stones or not. The sensitivity, specificity and predictive values were tested against postoperative NCCT. Predictors of accurate intraoperative assessment were determined using univariate and multivariate statistical analyses. RESULTS: The study included 306 consecutive patients. The surgeons reported no residual stones in 236 procedures; of whom 170 (72%) were reported stone-free by NCCT. On the other hand, 65 out of 70 procedures (93%) reported with residual stones by the surgeons were true by NCCT. The sensitivity was 50% and the NPV was 72%, while the specificity was 97% and the PPV was 93%. On multivariate analysis, only lower GSS (p < 0.001) was independently associated with true negative surgeon opinion. CONCLUSIONS: Although there was a high surgeon ability to detect post-PNL residual stones, postoperative imaging is mandatory because of the high false negative rates and low NPV. The surgeon opinions can be judged only in stones with lower GSS. The NPV could be enhanced if a consistent definition of clinically significant RFs is introduced.

Modulation of renal ischemia/reperfusion in rats by a combination of ischemic preconditioning and adipose-derived mesenchymal stem cells (ADMSCs).

The present study investigated the effects of combination of ischemic preconditioning (Ipre) and adipose-derived mesenchymal stem cells (ADMSCs) on renal ischemia-reperfusion (I-R) injury in rats. 90 male Sprague Dawley rats were divided into 5 equal groups; sham operated, control (45 min left renal ischemia), Ipre group as control group with 3 cycles of Ipre just before renal ischemia, ADMSCs-treated group (as control with ADMSCs 10(6) cells in 0.1 mL via penile vein 60 min before ischemia time), and Ipre + ADMSCs group as ADMCs group with 3 cycles of Ipre. Ipre and ADMSCs groups showed significant decrease in serum creatinine and blood urea nitrogen (BUN) and caspase-3 and CD45 expression in kidney and significant increase in HIF-1α, SDF-1α, CD31, and Ki67 expressions in kidney compared with the control group (p < 0.05). Moreover, the Ipre + ADMSCs group showed significant decrease in serum BUN and caspase-3 and CD45 expression in kidney with significant increase in HIF-1α, SDF-1α, CD31, and Ki67 expression in kidney compared with the Ipre and ADMCs groups (p < 0.05). We concluded that Ipre potentiates the renoprotective effect of ADMSCs against renal I/R injury probably by upregulation of HIF-1α, SDF-1α, CD31, and Ki67 and downregulation of caspase-3 and CD45.

A Review Comparing Experience and Results with Bipolar Versus Monopolar Resection for Treatment of Bladder Tumors.

The standard treatment of non-muscle invasive bladder cancer (NMIBC) is transurethral resection (TUR) commonly using a monopolar electrocautery system. This system requires high energy and voltage to allow an electric current to run from the loop to the patient's skin. The heat generated leads to desiccation of small cells and difficulty to perform adequate histological analysis for severely cauterized pieces of tissues. On contrary, the electric current in bipolar systems does not traverse the patient and hence lower energy and voltage are used and minimal tissue damage is anticipated. In addition, the use of saline as an irrigant fluid eliminates the potential TUR syndrome from excess hypotonic fluid reabsorption. Furthermore, the lower energy dissipates as heat in tissues contributing to adequate hemostasis. This review presents the most recent studies and evidence on the differences between monopolar and bipolar systems for TUR of NMIBC as regards the perioperative and long-term outcomes.

Remote limb ischemic preconditioning (rIPC) activates antioxidant and antiapoptotic genes and inhibits proinflammatory cytokine genes in renal ischemia/reperfusion injury.

The mechanisms underlying the renoprotective effect for remote limb ischemic preconditioning (rIPC) against renal ischemia/reperfusion injury need further elucidation. In our work, one hundred and twenty male Sprague Dawley rats were randomized into 3 groups; sham, I/R group (left renal 45 min ischemia) and rIPC (as I/R group with 3 cycles of left femoral ischemic PC just before renal ischemia). Rats were sacrificed at 2 h, 24 h, 48 h and 7 days. Serum creatinine and urea were measured at the baseline and endpoints. Also, histopathological examination and assessment of the expression of inflammatory cytokines e.g. TNF-α, IL-1ß and ICAM-1 and antioxidant genes: Nrf2, HO-1 and NQO-1 and anti-apoptotic gene Bcl-2 in left kidney were done by the end of experiment. The results of this study demonstrated that, rIPC caused significant improvement in serum creatinine and BUN levels and in the expression of antioxidant genes and Bcl-2 antiapoptotic gene with significant attenuation of pro-inflammatory cytokines and histopathological damage score at all-time points compared to I/R group (p ≤ 0.05). In conclusion, inhibition of inflammatory cytokine (TNF-α, IL-1ß and ICAM-1) formation and activation of antioxidant genes: Nrf2, HO-1 and NQO-1 and anti-apoptotic gene Bcl-2 could be possible underlying mechanisms for the renoprotective effect of rIPC.

External stent versus double J drainage in patients with radical cystectomy and orthotopic urinary diversion: A randomized controlled trial.

OBJECTIVES: To compare treatment-related outcomes of ureteral stenting with an external versus double J stent in patients with orthotopic reservoirs after radical cystectomy. METHODS: Patients undergoing radical cystectomy and orthotopic neobladder were randomized into two groups; group I patients received external stents, whereas group II received double J stents. In both groups, preoperative parameters were recorded, and patients were assessed regarding urinary tract infection, urinary leakage, upper tract deterioration, readmission and hospital stay. RESULTS: A total of 48 and 45 patients were randomized in the external stent group and double J group, respectively. Both groups were comparable in terms of age, sex, associated comorbidity and oncological status. Early urinary leak was observed in two patients (4.2%) in the external stent group, and in two patients (4.4%) in the double J group (P = 0.95). None of our patients developed ureteral strictures in the external stent group, and one patient did in the double J group (P = 0.3). Positive urine culture (58.3%, 51.1%) as well as febrile urinary tract infections (2.1%, 6.7%) were comparable between both groups, respectively (P = 0.43, 0.28). Wound complications (12.5%, 8.9%) and stent-related complications (2.1%, 0%) were comparable between both groups, respectively (P = 0.57, 0.33). The mean hospital stay was 17.5 days (range 14-32 days) and 14.6 days (range 10-42 days) in both groups, respectively (P = 0.001), with comparable re-admission rates (P = 0.95). CONCLUSIONS: Incorporation of double J stents in orthotopic urinary diversion is a safe alternative to the routinely used external stenting.

Risk factors of hospital readmission after radical cystectomy and urinary diversion: analysis of a large contemporary series.

OBJECTIVES: To determine the incidence, risk factors and causes of hospital readmission in a large series of patients who underwent radical cystectomy (RC) and urinary diversion. PATIENTS AND METHODS: We retrospectively analysed the data of 1000 patients who underwent RC and urinary diversion between January 2004 and September 2009 in our tertiary referral centre. Patients stayed in hospital for 21 and 11 days for orthotopic and ileal conduit diversions, respectively. The primary outcome was the development of a complication requiring hospital readmission at ≤3 months (early) and >3 months (late). Causes of hospital readmissions were categorised according to frequency of readmissions. Predictors were determined using univariate and multivariate logistic regression models. RESULTS: In all, 895 patients were analysed excluding 105 patients because of perioperative mortality and loss to follow-up. Early and late readmissions occurred in 8.6% and 11% patients, respectively. The commonest causes of first readmission were upper urinary tract obstruction (UUO, 13%) and pyelonephritis (12.4%) followed by intestinal obstruction (11.9%) and metabolic acidosis (11.3%). The development of postoperative high-grade complications (odds ratio [OR] 1.955; 95% confidence interval [CI] 1.254-3.046; P = 0.003) and orthotopic bladder substitution (OR 1.585; 95% CI 1.095-2.295; P = 0.015) were independent predictors for overall hospital readmission after RC. Postoperative high-grade complications (OR 2.488; 95% CI 1.391-4.450; P = 0.002), orthotopic bladder substitution (OR 2.492; 95% CI 1.423-4.364; P = 0.001) and prolonged hospital stay (OR 1.964; 95% CI:1.166-3.308; P = 0.011) were independent predictors for early readmission while hypertension (OR 1.670; 95% CI 1.007-2.769; P = 0.047) was an independent predictor for late readmission. CONCLUSION: Hospital readmissions are a significant problem after RC. In the present study, UUO, pyelonephritis, metabolic acidosis and intestinal obstruction were the main causes of readmission. Orthotopic bladder substitution and development of postoperative high-grade complications were significant predictors for overall readmission.

Can computerized tomography accurately stage childhood renal tumors?

PURPOSE: Staging of childhood renal tumors is crucial for treatment planning and outcome prediction. We sought to identify whether computerized tomography could accurately predict the local stage of childhood renal tumors. MATERIALS AND METHODS: We retrospectively reviewed our database for patients diagnosed with childhood renal tumors and treated surgically between 1990 and 2013. Inability to retrieve preoperative computerized tomography, intraoperative tumor spillage and nonWilms childhood renal tumors were exclusion criteria. Local computerized tomography stage was assigned by a single experienced pediatric radiologist blinded to the pathological stage, using a consensus similar to the Children's Oncology Group Wilms tumor staging system. Tumors were stratified into up-front surgery and preoperative chemotherapy groups. The radiological stage of each tumor was compared to the pathological stage. RESULTS: A total of 189 tumors in 179 patients met inclusion criteria. Computerized tomography staging matched pathological staging in 68% of up-front surgery (70 of 103), 31.8% of pre-chemotherapy (21 of 66) and 48.8% of post-chemotherapy scans (42 of 86). Computerized tomography over staged 21.4%, 65.2% and 46.5% of tumors in the up-front surgery, pre-chemotherapy and post-chemotherapy scans, respectively, and under staged 10.7%, 3% and 4.7%. Computerized tomography staging was more accurate in tumors managed by up-front surgery (p <0.001) and those without extracapsular extension (p <0.001). CONCLUSIONS: The validity of computerized tomography staging of childhood renal tumors remains doubtful. This staging is more accurate for tumors treated with up-front surgery and those without extracapsular extension. Preoperative computerized tomography can help to exclude capsular breach. Treatment strategy should be based on surgical and pathological staging to avoid the hazards of inaccurate staging.

Impact of the type of ureteroileal anastomosis on renal function measured by diuretic scintigraphy: long-term results of a prospective randomized study.

OBJECTIVE: To determine the long-term effects of the direct refluxing-type ureteroileal anastomosis technique with those of an antireflux technique on individual renal units, using diuretic scintigraphy in a prospectively randomized study. PATIENTS AND METHODS: Between 2002 and 2006, a prospective randomized study was conducted on 102 patients undergoing radical cystectomy and urinary diversion. In every patient, both ureters were randomized to be implanted using a direct refluxing technique or an antireflux, serous-lined extramural tunnel (SLET) technique. Renal function (RF) was evaluated using (99m)Tc-MAG-3 diuretic scintigraphy. The serial changes in corrected glomerular filtration rate (cGFR) for each technique and for each side were compared. RESULTS: Over a median follow-up of 6 years, the patients in both the direct refluxing and the SLET technique groups were found to have a significant reduction in mean (SD) cGFR between baseline and last follow-up: cGFR decreased from 59.4 (12.4) to 45.6 (15.3) mL/min (P < 0.001) and from 54.3 (11.2) to 46.3 (12.8) mL/min (P = 0.002), respectively. Five patients (4.9%) in the SLET group developed obstruction (four left-sided and one right-sided) compared with one (0.9%) in the direct refluxing group (right-sided). The onset of obstruction was noted 1-7 months after radical cystectomy. There was no significant difference between the groups in reductions in cGFR across the timepoints. Comparison of the two techniques according to the side of ureter implantation showed that the direct refluxing technique trended towards better functional outcomes on the left side. CONCLUSIONS: There was no observed difference in the RF of individual renal units between the SLET and the direct refluxing groups in the long term. The need to incorporate an antireflux technique should be questioned and tailored according to the surgeon's experience and confidence.

Renal function evaluation in patients undergoing orthotopic bladder substitution: a systematic review of literature.

Renal function (RFn) after orthotopic bladder substitution (OBS) is a critical point to be assessed. We performed a systematic review of MEDLINE for full length peer reviewed English articles from the year 2000 till January 2013. We included only original articles and excluded reviews, editorials and replies and abstracts presented in conferences. The outcome is formulated in research questions; what is the status of RFn after OBS? Which is better, the direct free-refluxing or anti-refluxing ureteroileal anastomosis (UIA) techniques? Studies reporting RFn as secondary outcome were also reported. A total of 129 publications were reviewed for full text and only 41 were included in this review. All studies were of low level of evidence and grade of recommendations. Only 3 randomized controlled trials were included and were of poor quality. Renal function after OBS was poorly described in the literature with no universal definition about RFn deterioration or outcome with no consensus on the best evaluation method. Urinary obstruction, chemotherapy and pyelonephritis appeared significant factors but with insufficient evidence. There is a universal trend to use the free refluxing technique for UIA to avoid complications of anti-refluxing techniques. However, the anti-reflux technique proved acceptable outcome in experienced hands. There is marked heterogeneity and underestimation of RFn evaluation among reported outcomes after OBS with most publications reporting the incidence of UIA and pyelonephritis with paucity reporting absolute figures about RFn measurements. In conclusion, urinary tract obstruction remains the main factor of RFn deterioration after OBS. Methods evaluating RFn, definitions of RFn outcome and factors predicting it are poorly studied in the literature and the current evidence is relatively weak to draw solid conclusions. Further well-designed studies and consensus about method of assessment and definitions of RFn are warranted.

Evaluation of factors predicting recoverability of renal function after pyeloplasty in adults.

AIM: To analyze the status of renal function after pyeloplasty in a large contemporary adult series and to detect which variables predict improvement of renal function. MATERIALS AND METHODS: 85 adult patients were retrospectively identified who had undergone pyeloplasty between January 2002 and May 2011 with available pre- and postoperative diuretic scintigraphy. Preoperative differential renal function (DRF) and single-kidney GFR (SKGFR) were obtained by (99m)Tc-MAG-3 diuretic scintigraphy. Baseline-weighted (bw-) DRF and SKGFR were calculated between baseline conditions and time of last follow-up. Factors that explain the variance of bw-DRF and bw-SKGFR were determined. RESULTS: The mean (SD) preoperative DRF significantly increased from 34% (11.6) to 37.2% (11.8) after pyeloplasty (p < 0.001). Similarly, mean (SD) SKGFR showed a significant improvement from 31.2 (12.9) to 35.9 (15) ml/min (p < 0.001). Patients with a lower baseline DRF (≤40%) showed a significant improvement as opposed to those with a higher baseline DRF (>40%) (p < 0.001 and 0.3, respectively). Baseline DRF and cortical thickness explained the variance in bw-DRF and bw-SKGFR with more contribution of baseline DRF. CONCLUSIONS: Renal function showed improvement after pyeloplasty in adults and preoperative DRF and cortical thickness were the predicting variables.

Salvage of grafts with vascular thrombosis during live donor renal allotransplantation: a critical analysis of successful outcome.

OBJECTIVES: To report a high-volume institution experience with salvage techniques for vascular accidents during live donor renal allotransplantation. METHODS: Between March 1976 and January 2011, 2208 recipients underwent live donor renal allotransplantation. A retrospective review of recipients with vascular accidents - renal artery thrombosis and renal vein thrombosis - was carried out. Salvage procedures were recorded and their outcomes were assessed. RESULTS: A total of 23 (1%) vascular accidents occurred, including renal artery thrombosis and renal vein thrombosis in 19 (0.8%) and four (0.18%) recipients, respectively. All renal artery thrombosis patients were treated by open revascularization and the graft was salvaged in 12 patients (63%). Two renal vein thrombosis events were resolved by percutaneous catheter-directed thrombolytic therapy. Of the other two allografts, one was salvaged by thrombectomy and revascularization, and the other was lost. On univariable analysis, older recipients (P = 0.003), pretransplant hypertension (P = 0.001), more human leukocyte antigen mismatches (≥3; P = 0.036), shorter ischemia time (≤45 min; P = 0.004) and longer time to diagnosis (>3.5 days; P = 0.013) were significantly associated with non-salvage of the graft after vascular accidents. Nevertheless, none of these variables were significant on the multivariable analysis. Over a median follow up of 35 months, the median (range) serum creatinine was 2 mg/dL (range 0.8-8.8 mg/dL), and 11 (79%) recipients were living with functioning grafts. CONCLUSIONS: Despite the devastating complications, vascular accidents are salvageable and revascularization is crucial for graft salvage. Angiographic percutaneous techniques are viable alternatives for renal vein thrombosis.

The impact of chemotherapy-naïve open radical cystectomy delay and perioperative transfusion on the recurrence-free survival: A perioperative parameters-based nomogram.

Objective: To develop and internally validate a nomogram to predict recurrence-free survival (RFS) including the time to radical cystectomy (RC) and perioperative blood transfusion (PBT) as potential predictors. Methods: Patients who underwent open RC and ileal conduit between January 1996 to December 2016 were split into developing (n=948) and validating (n=237) cohorts. The time to radical cystectomy (TTC) was defined as the interval between the onset of symptoms and RC. The regression coefficients of the independent predictors obtained by Cox regression were used to construct the nomogram. Discrimination, validation, and clinical usefulness in the validation cohort were assessed by the area under the curve, the calibration plot, and decision curve analysis. Results: In the developing dataset, the 1-, 5-, and 10-year RFS were 83.0%, 47.2%, and 44.4%, respectively. On multivariate analysis, independent predictors were TTC (hazards ratio [HR] 1.07, 95% confidence interval [CI] 1.05-1.08, p<0.001), PBT (one unit: HR 1.40, 95% CI 1.03-1.90, p=0.03; two or more units: HR 1.72, 95% CI 1.29-2.29, p<0.001), bilateral hydronephrosis (HR 1.54, 95% CI 1.21-1.97, p<0.001), squamous cell carcinoma (HR 0.60, 95% CI 0.45-0.81, p=0.001), pT3-T4 (HR 1.77, 95% CI 1.41-2.22, p<0.001), lymph node status (HR 1.53, 95% CI 1.21-1.95, p<0.001), and lymphovascular invasion (HR 1.28, 95% CI 1.01-1.62, p=0.044). The areas under the curve in the validation dataset were 79.3%, 69.6%, and 76.2%, for 1-, 5-, and 10-year RFS, respectively. Calibration plots showed considerable correspondence between predicted and actual survival probabilities. The decision curve analysis revealed a better net benefit of the nomogram. Conclusion: A nomogram with good discrimination, validation, and clinical utility was constructed utilizing TTC and PBT in addition to standard pathological criteria.

Anti-sperm Antibody Positivity in Men with Varicocele: A Systematic Review and Meta-Analysis.

PURPOSE: Despite the significant role of varicocele in the pathogenesis of male infertility, its association with anti-sperm antibodies (ASA) remains controversial. This systematic review and meta-analysis (SRMA) aims to investigate the frequency of ASA positivity in men with varicocele. MATERIALS AND METHODS: This SRMA is conducted in accordance with the Meta-analysis of Observational Studies in Epidemiology guidelines. We investigated the frequency of ASA positivity in ejaculates or serum of men with varicocele as compared to men without varicocele (controls). A literature search was performed using the Scopus and PubMed databases following the Population Exposure Comparison Outcome, Study Design model. Data extracted from eligible studies were meta-analyzed and expressed as odds ratios (ORs) and confidence intervals (CIs). RESULTS: Out of 151 abstracts identified during the initial screening, 6 articles met the inclusion criteria and were included in the meta-analysis. Using mixed antiglobulin reaction (MAR) assay, 61 out of the 153 (39.8%) patients with varicocele tested positive for ASA in their ejaculates as compared to 22 out of the 129 control subjects (17%, OR=4.34 [95% CI: 1.09-17.28]; p=0.04). Using direct or indirect immunobead test, 30 out of 60 cases diagnosed with varicocele (50%) had shown ASA positivity in their ejaculates as compared to 16 out of 104 controls (15.4%, OR=3.57 [95% CI: 0.81-15.68]; p=0.09). Using enzyme-linked immunosorbent assay (ELISA), out of 89 varicocele patients, 33 (37.1%) tested positive for serum ASA as compared to 9 out of 57 participants in the control group (15.8%, OR=7.87 [95% CI: 2.39-25.89]; p<0.01). CONCLUSIONS: This SRMA indicates that ASA positivity is significantly higher among men with varicocele when tested by direct method (MAR) or indirect method (ELISA). This data suggests an immunological pathology in infertile men with varicocele and may have implications for the management of these patients.

Impact of Varicocele on Testicular Oxidative Stress and Sperm Parameters in Experimental Animals: A Systematic Review and Meta-Analysis.

PURPOSE: Varicocele has been associated with high seminal oxidative stress (OS), impaired semen quality, and reduced male fertility potential. However, the exact mechanism(s) underlying the development of varicocele-mediated infertility and the cause-effect relationship between varicocele and testicular dysfunction are not fully understood. The aim of this systematic review and meta-analysis (SRMA) is to investigate the impact of varicocele on testicular OS markers and sperm parameters in experimental animals with varicocele as compared to animals without varicocele. MATERIALS AND METHODS: A literature search was performed using the Scopus and PubMed databases on studies that investigated testicular OS markers and sperm parameters in animals with varicocele. The primary outcomes included malondialdehyde (MDA) (nmol/mg) levels whereas the secondary outcomes included total sperm count (×106), sperm vitality (%), total sperm motility (%), and sperm DNA fragmentation (SDF) (%). Standardized mean difference (SMD) (95% confidence interval [CI]) was chosen to express the effect size. The quality of the included studies was evaluated using the Cambridge Quality Checklist. RESULTS: Out of 76 identified articles, 6 studies on rats were included in the meta-analysis. The analysis showed a significant increase of MDA (SMD: 15.61 [1.93, 29.29]; p=0.03) in rats with varicocele vs. controls. We also observed a significant decrease in total sperm count (SMD: -17.45 [-28.97, -5.93]; p<0.01), sperm vitality (SMD: -16.41 [-26.30, -6.52]; p<0.01), total sperm motility (SMD: -17.67 [-24.90, -10.44]; p<0.01), and a significant increase of SDF (SMD: 7.41 [1.23, 13.59]; p=0.02), in rats with varicocele vs. controls. The quality of the included studies was ranked as high. CONCLUSIONS: This SRMA indicates a significant increase in levels of testicular MDA and SDF and a reduction of sperm quality in experimental animals with varicocele. These findings support the potential role of testicular OS in the development of varicocele-induced testicular damage.

Effects of Varicocele Repair on Sperm DNA Fragmentation and Seminal Malondialdehyde Levels in Infertile Men with Clinical Varicocele: A Systematic Review and Meta-Analysis.

PURPOSE: Varicoceles can be a source of elevated seminal oxidative stress (OS) and sperm DNA fragmentation (SDF). However, it remains unclear whether varicocele repair (VR) could reduce these parameters. This systematic review and meta-analysis (SRMA) aims to investigate the impact of VR on SDF and seminal malondialdehyde (MDA). MATERIALS AND METHODS: A literature search was performed in Scopus, PubMed, Ovid, Embase, and Cochrane databases. This SRMA included randomized controlled trials and observational studies reporting the pre- and postoperative levels of SDF and seminal OS in infertile men with clinical varicocele that underwent VR. Subgroup analyses included techniques of VR and SDF testing. The effect size was expressed as standardized mean difference (SMD). RESULTS: Out of 1,632 abstracts assessed for eligibility, 29 studies with 1,491 infertile men were included. The analysis showed a significant reduction in SDF after VR, compared to preoperative values (SMD -1.125, 95% confidence interval [CI] -1.410, -0.840; p<0.0001) with high inter-study heterogeneity (I²=90.965%). Reduction in SDF was evident with microsurgical technique and non-microsurgical inguinal approaches (SMD -1.014, 95% CI -1.263, -0.765; p<0.0001, and SMD -1.495, 95% CI -2.116, -0.873; p<0.0001), respectively. Reduction in SDF was significant irrespective of testing was done by sperm chromatin dispersion (SMD -2.197, 95% CI -3.187, -1.207; p<0.0001), sperm chromatin structure assay (SMD -0.857, 95% CI -1.156, -0.559; p<0.0001) or TUNEL (SMD -1.599, 95% CI -2.478, -0.719; p<0.0001). A significant decrease in seminal MDA levels was observed following VR (SMD -2.450, 95% CI -3.903 to -0.997, p=0.001) with high inter-study heterogeneity (I²=93.7%). CONCLUSIONS: Using pre- and post-intervention data, this SRMA indicates a significant reduction in SDF and seminal MDA levels in infertile men with clinical varicocele treated with VR. These findings may have important implications for the future management of this selected group of infertile patients.

Technical Aspects and Clinical Limitations of Sperm DNA Fragmentation Testing in Male Infertility: A Global Survey, Current Guidelines, and Expert Recommendations.

PURPOSE: Sperm DNA fragmentation (SDF) is a functional sperm abnormality that can impact reproductive potential, for which four assays have been described in the recently published sixth edition of the WHO laboratory manual for the examination and processing of human semen. The purpose of this study was to examine the global practices related to the use of SDF assays and investigate the barriers and limitations that clinicians face in incorporating these tests into their practice. MATERIALS AND METHODS: Clinicians managing male infertility were invited to complete an online survey on practices related to SDF diagnostic and treatment approaches. Their responses related to the technical aspects of SDF testing, current professional society guidelines, and the literature were used to generate expert recommendations via the Delphi method. Finally, challenges related to SDF that the clinicians encounter in their daily practice were captured. RESULTS: The survey was completed by 436 reproductive clinicians. Overall, terminal deoxynucleotidyl transferase deoxyuridine triphosphate Nick-End Labeling (TUNEL) is the most commonly used assay chosen by 28.6%, followed by the sperm chromatin structure assay (24.1%), and the sperm chromatin dispersion (19.1%). The choice of the assay was largely influenced by availability (70% of respondents). A threshold of 30% was the most selected cut-off value for elevated SDF by 33.7% of clinicians. Of respondents, 53.6% recommend SDF testing after 3 to 5 days of abstinence. Although 75.3% believe SDF testing can provide an explanation for many unknown causes of infertility, the main limiting factors selected by respondents are a lack of professional society guideline recommendations (62.7%) and an absence of globally accepted references for SDF interpretation (50.3%). CONCLUSIONS: This study represents the largest global survey on the technical aspects of SDF testing as well as the barriers encountered by clinicians. Unified global recommendations regarding clinician implementation and standard laboratory interpretation of SDF testing are crucial.

Artificial Intelligence in Andrology: From Semen Analysis to Image Diagnostics.

Artificial intelligence (AI) in medicine has gained a lot of momentum in the last decades and has been applied to various fields of medicine. Advances in computer science, medical informatics, robotics, and the need for personalized medicine have facilitated the role of AI in modern healthcare. Similarly, as in other fields, AI applications, such as machine learning, artificial neural networks, and deep learning, have shown great potential in andrology and reproductive medicine. AI-based tools are poised to become valuable assets with abilities to support and aid in diagnosing and treating male infertility, and in improving the accuracy of patient care. These automated, AI-based predictions may offer consistency and efficiency in terms of time and cost in infertility research and clinical management. In andrology and reproductive medicine, AI has been used for objective sperm, oocyte, and embryo selection, prediction of surgical outcomes, cost-effective assessment, development of robotic surgery, and clinical decision-making systems. In the future, better integration and implementation of AI into medicine will undoubtedly lead to pioneering evidence-based breakthroughs and the reshaping of andrology and reproductive medicine.