Effect of ureteric access sheath on outcomes of retrograde intrarenal surgery for renal stone disease: a randomized controlled trial.

BACKGROUND: The need of ureteric access sheath (UAS) in retrograde intrarenal surgery (RIRS) has been controversial for gaining high success in terms of stone free rate (SFR), reducing operative times and complications. There has been lack of high level of evidence in the literature on this topic. MATERIALS AND METHODS: This prospective randomized controlled trial (RCT) was conducted in the Department of Urology, PGIMER, Chandigarh from July 2019 to Dec 2021. The effect of UAS on the outcome of RIRS (SFR, operative time and complications) for renal stone disease was assessed. Ninety patients were randomized into two groups: 41 patients in Group 1 (RIRS with UAS) and 40 patients in Group 2(RIRS without UAS) were finally analyzed after exclusion. All the patients underwent preoperative double J stent placement at least 10 days prior to the definitive procedure. Operative time was recorded and postoperative pain was assessed by visual analogue scale(VAS) at 6 and 24 h postoperatively. Complications and emergency visits were recorded up to one month post procedure. SFR was assessed at 1 month using noncontrast CT KUB. Success was defined as absence of any residual fragment more than 3 mm in maximum diameter. RESULTS: Demographic parameters (age, body mass index, and comorbidities) and preoperative parameters (stone burden, proportion of recurrent stone formers and proportion of patients with inferior calyceal stones) were comparable between the two groups. Operative times (45.49 vs 48.38 min; p - 0.484) and VAS scores at 6 and 24 h post-op (p - 0.577) were also comparable between Group 1 and Group 2. SFR was comparable in Group 1 and Group 2 (78.05% vs 80%, p - 0.829). Postoperative complications were higher in the UAS group, but not statistically significant (4.88% vs 0%; p - 0.157). CONCLUSION: The use of UAS during RIRS is not associated with improved SFR. RIRS can be performed safely without the use of UAS and without increasing postoperative complications.

Safety and Diagnostic Yield of 68Ga Prostate-specific Membrane Antigen PET/CT-guided Robotic-assisted Transgluteal Prostatic Biopsy.

Background Transrectal US-guided biopsy with or without MRI fusion is performed for diagnosing prostate cancer (PCa) but has limitations. Gallium 68 (68Ga) prostate-specific membrane antigen (PSMA) PET/CT-guided targeted biopsy has the potential to improve diagnostic yield of PCa. Purpose To evaluate the safety and diagnostic yield of 68Ga PSMA PET/CT-guided, robotic-arm assisted transgluteal prostatic biopsy. Materials and Methods In this single-center nonrandomized prospective trial, participants with a clinical suspicion of PCa (serum prostate-specific antigen level > 4 ng/mL) were recruited from January 2019 to September 2020. After whole-body 68Ga PSMA PET/CT, participants with PSMA-avid intraprostatic lesions underwent PET-guided transgluteal biopsy by using an automated robotic arm. To assess safety and diagnostic yield, procedure-related complications and histopathologic results were documented. Pain during the procedure was scored by a visual analog scale. Descriptive statistics were applied; qualitative variables were reported in percentages. Results Seventy-eight participants (mean age, 66 years ± 7 [standard deviation]; 36 participants [46%] with prior negative results at transrectal US-guided biopsy) were enrolled. Fifty-six (72%) participants had PSMA-avid lesions (prior negative results at transrectal US-guided biopsy in 22 of 56 [39%]) and underwent targeted biopsy. PCa was confirmed in 54 of 56 (96%) participants, and clinically significant PCa (Gleason score ≥ 7) was confirmed in 24 of 54 (44%). Two participants had nonrepresentative samples that required rebiopsy. All participants experienced pain during the procedure, mild (median visual analog scale score, 1; interquartile range, 1-2) in 36 of 56 (64%) and moderate (median visual analog scale score, 5; interquartile range, 5-6) in 20 of 56 (36%). Postprocedure complications were noted in five of 56 (9%) participants and were minor (hematuria, four participants; hematospermia, one participant; and gluteal pain, two participants). No participant developed a postprocedural infection. Conclusion Transgluteal prostate-specific membrane antigen (PSMA) PET/CT-guided, robotic-targeted prostatic biopsy is safe with a high diagnostic yield of prostate cancer for PSMA-avid lesions. Clinical trial registration no. NCT05022576 © RSNA, 2022.

177Lu-PSMA-617 versus docetaxel in chemotherapy-naïve metastatic castration-resistant prostate cancer: a randomized, controlled, phase 2 non-inferiority trial.

PURPOSE: Lutetium-177 prostate-specific membrane antigen-617 (177Lu-PSMA-617) in end-stage metastatic castration-resistant prostate cancer (mCRPC) has reported favourable outcomes. In this study, we aimed to prospectively compare the efficacy and safety of 177Lu-PSMA-617 and docetaxel in chemotherapy-naïve mCRPC patients. METHODS: This was a randomized, parallel-group, open-label, phase 2, and non-inferiority trial. Chemotherapy-naïve patients with mCRPC and high PSMA-expressing lesions on 68 Ga-PSMA-11 PET/CT were randomly assigned in 1:1 ratio to 177Lu-PSMA-617 (6.0-7.4 GBq/cycle, every 8 weeks, up to 4 cycles) or docetaxel (75 mg/m2/cycle, every 3 weeks, up to 10 cycles). The primary end-point was best prostate-specific antigen response rate (PSA-RR), defined according to Prostate Cancer Clinical Trials Working Group-3 as proportion of patients achieving ≥ 50% decline in PSA from baseline. Non-inferiority margin of - 15% was pre-specified for PSA-RR. RESULTS: Between December 2019 and March 2021, 40 of the 45 patients assessed for eligibility underwent randomization. Fifteen of 20 patients in 177Lu-PSMA-617 arm and 20/20 patients in docetaxel arm received treatment per protocol. Of these, best PSA-RR in the 177Lu-PSMA-617 arm was 60% (9/15) versus 40% (8/20) in the docetaxel arm. The difference in the PSA-RRs between the two arms was 20% (95% confidence interval, CI: - 12-47, P = 0.25), meeting the pre-specified criterion for non-inferiority in per-protocol analysis. Further, progression-free survival rates at 6 months were 30% and 20% in the 177Lu-PSMA-617 and docetaxel arms respectively (difference 10%, 95% CI: - 18-38, P = 0.50). Overall, treatment-emergent grade ≥ 3 adverse events occurred less frequently with 177Lu-PSMA-617 than with docetaxel (6/20, 30% versus 10/20, 50%, respectively, P = 0.20). Quality-of-life outcomes improved significantly in 177Lu-PSMA-617 arm compared to docetaxel arm (P < 0.01). CONCLUSION: 177Lu-PSMA-617 was demonstrated to be safe and non-inferior to docetaxel in the treatment of mCRPC and could, thus, be potentially employed earlier in the disease course rather than being solely reserved for advanced end-stage disease. CLINICAL TRIAL REGISTRATION: Clinical Trials Registry-India, CTRI/2019/12/022282.

'Pee'BuSt Trial: A single-centre prospective randomized study comparing functional and anatomic outcomes after augmentation urethroplasty with penile skin graft versus buccal mucosa graft for anterior urethral stricture disease.

PURPOSE: To assess the surgical outcomes of augmentation urethroplasty (AU) using penile skin graft (PSG) compared to buccal mucosa graft (BMG) in anterior urethral stricture disease. METHOD: Between January 2018 and January 2019, 100 patients with anterior urethral stricture planned for AU were randomized into PSG or BMG arms (CTRI/2018/07/015028). Anatomic and functional variables were compared pre-operatively and post-operatively. Primary outcome was success rate at 18 months and it was defined if any of the three criteria were met, i.e. either maximum urinary flow (Qmax) > 15 ml/s or urethral calibration of 16 French or ability to traverse the repair with 17 French cystoscope. Secondary outcomes were functional parameters such as International Prostate Symptom Score (IPSS), International Index of Erectile Function (IIEF) Score, Male Sexual Health Questionnaire for Ejaculatory Dysfunction (MSHQ-EJD), and Urethral Stricture Surgery-Patient Related Outcome Measure (USS-PROM). RESULTS: Pre-operative variables were comparable between both the arms. Median duration of follow-up was 22 months (18-24 months). At 18 months, the success rates of AU with PSG and BMG were comparable (89% v/s 91%; p = 0.70, 95% CI-0.33 to 5.21). The improvements in Qmax (p = 0.06), IPSS (p = 0.43) and USS-PROM (p = 0.49) were comparable between the two arms. There was no statistically significant difference in the IIEF-Erectile domain (p = 0.07), IIEF-Orgasmic domain (p = 0.11) and MSHQ-EJD (p = 0.20) following AU at 18 months. Clavien-Dindo grade I complications were 12.7% in PSG and 16.7% in BMG. CONCLUSION: This study provides level 1 evidence of no statistical significant difference in outcomes of AU using BMG or PSG.

Spontaneous Erosion of Retained Bone Chip into Anal Canal Following Progressive Perineal Urethroplasty with Inferior Pubectomy: Lessons Learnt!

We present a never before reported delayed complication of progressive perineal urethroplasty with inferior pubectomy in a young male, where retained bone chip spontaneously erodes through anal canal. Our case cautions urologists doing inferior pubectomy for pelvic fracture urethral distraction defect to make sure that no loose bony fragment is left in the operative field. We also emphasize to make sure to nibble the sharp bony margins of the cut pubic bone after inferior pubectomy so that it will not impinge onto the anterior wall of rectum eliminating the risk of delayed perforation of rectum or anal canal.

Impact of pathological factors on survival in patients with upper tract urothelial carcinoma: a systematic review and meta-analysis.

INTRODUCTION: There is an ongoing need to identify various pathological factors that can predict various survival parameters in patients with upper tract urothelial carcinoma (UTUC). With this review, we aim to scrutinize the impact of several pathological factors on recurrence free survival (RFS), cancer-specific survival (CSS) and overall survival (OS) in patients with UTUC. MATERIALS AND METHODS: Systematic electronic literature search of various databases was conducted for this review. Studies providing multivariate hazard ratios (HR) for various pathological factors such as tumor margin, necrosis, stage, grade, location, architecture, lymph node status, lymphovascular invasion (LVI), carcinoma in situ (CIS), multifocality and variant histology as predictor of survival parameters were included and pooled analysis of HR was performed. RESULTS: In this review, 63 studies with 35.714 patients were included. For RFS, all except tumor location (HR 0.94, p=0.60) and necrosis (HR 1.00, p=0.98) were associated with worst survival. All the pathological variables except tumor location (HR 0.95, p=0.66) were associated with worst CSS. For OS, only presence of CIS (HR 1.03, p=0.73) and tumor location (HR 1.05, p=0.74) were not predictor of survival. CONCLUSIONS: We noted tumor grade, stage, presence of LVI, lymph node metastasis, hydronephrosis, variant histology, sessile architecture, margin positivity and multifocality were associated with poor RFS, CSS and OS. Presence of CIS was associated with poor RFS and CSS but not OS. Tumor necrosis was associated with worst CSS and OS but not RFS. Tumor location was not a predictor of any of the survival parameters.

Iatrogenic partial glanular amputation: A rare complication of circumcision.

Circumcision is a customary ritual across many cultures. However, the safety of such procedures remains a concern. A boy underwent circumcision in 2014 by a religious worker at the age of 7 years. Post circumcision, the patient had gradual narrowing of the penis, between the glans and the shaft, with an iatrogenic partial glanular amputation and presented to us at the age of 14 years. The patient underwent end-to-end urethroplasty and glansplasty. Postoperatively, the patient did well and the wound remained healthy. Circumcision has complications even in expert hands. Religious circumcision can result in dreadful complications in children and adolescents.

Long-term impact of testicular torsion and its salvage on semen parameters and gonadal function.

Introduction: Testicular torsion is a urological emergency, and long-term outcomes of testicular torsion on infertility, hormonal function, and salvaged testicular size are unclear. Materials and Methods: We conducted an ambispective, observational study from January 2014 to December 2019. Baseline demographics, time of presentation, clinical features, and management details of all the patients of testicular torsion were recorded from the database. All the patients were followed up in the outpatient clinic for testicular size, hormone levels, semen analysis, and erectile function. Results: Of 85 patients, only 67 could be contacted and included in the final analysis. Group 1(orchiectomy) comprised 44 patients, and Group 2(salvage) had 23 patients. Follow-up duration ranged from 2 to 6 years and mean follow-up was 42 ± 12 months. The median time to presentation was significantly higher in Group 1 (48 hours) as compared to Group 2 (12 hours). The rate of testicular salvage did not vary with age of the patients. Doppler ultrasonography of the scrotum detected 92.5% of all cases of torsion. Antisperm antibody levels were within normal range in all patients. Approximately 47% of patients in the salvage group developed testicular atrophy on follow-up. Serum testosterone level was significantly lower in Group 1 and the subset of patients with testicular atrophy. Rest of the hormonal parameters, semen analysis, and erectile function were comparable between two groups. Conclusion: The time between onset and presentation is an important contributing factor in guiding testicular salvage. Even after salvage, many testes may atrophy on follow-up. Orchiectomy and testicular atrophy in the long term have negative impact on serum testosterone. The patients should be counseled for a long-term follow-up for the risk of testicular atrophy and low testosterone levels.

Robot-assisted partial nephrectomy for moderate to highly complex renal masses. A systematic review and meta-analysis.

Introduction: Multiple studies have been published recently assessing feasibility of robot-assisted partial nephrectomy (RAPN) for moderate to highly complex renal masses. Some studies have even compared partial nephrectomy (PN) performed through various modalities such as open PN (OPN) versus RAPN and laparoscopic PN (LPN) versus OPN. The primary aim of this review was to analyze perioperative outcomes such as warm ischemia time (WIT), duration of surgery, estimated blood loss (EBL), complications, blood transfusion, length of stay, and margin status following RAPN for complex renal masses. Another objective was to compare perioperative outcomes following various surgical modalities, i.e., OPN, LPN, or RAPN. Methods: Literature search was conducted to identify studies reporting perioperative outcomes following RAPN for moderate (Radius, Endophytic/Exophytic, Nearness, Anterior/posterior location [RENAL] score 7-9 or Preoperative Aspects of Dimension used for anatomic classification [PADUA] score 8-9) to high complexity renal masses (RENAL or PADUA score ≥ 10). Meta-analysis of robotic versus OPN and robotic versus LPN was also performed. Study protocol was registered with PROPSERO (CRD42019121259). Results: In this review, 22 studies including 2,659 patients were included. Mean duration of surgery, WIT, and EBL was 132.5-250.8 min, 15.5-30 min, and 100-321 ml, respectively. From pooled analysis, positive surgical margin, need for blood transfusion, minor and major complications were seen in 3.9%, 5.2%, 19.3%, and 6.3% of the patients. No significant difference was noted between RAPN and LPN for any of the perioperative outcomes. Compared to OPN, RAPN had significantly lower EBL, complications rate, and need for transfusion. Conclusions: RAPN for moderate to high complexity renal masses is associated with acceptable perioperative outcomes. LPN and RAPN were equal in terms of perioperative outcomes for complex masses whereas, OPN had significantly higher blood loss, complications rate, and need for transfusion as compared to RAPN.

Dorsolateral inner preputial graft urethroplasty for anterior urethral strictures: long-term outcomes from a single tertiary care centre.

PURPOSE: Buccal mucosa graft (BMG) is long used as favoured substitute by most reconstructive surgeons for substitution urethroplasty (SU). Though inner preputial skin graft (IPG) was described even earlier than BMG, its usage lately has fallen out of favour. The aim of the study was to evaluate the outcome of a SU with IPG from a tertiary care centre. METHODS: A retrospective analysis of prospectively maintained clinical data was conducted at our tertiary care centre enrolling 80 patients with anterior urethral stricture from January 2015 to January 2018. Patients were evaluated for the aetiology, length and site of the urethral stricture. All patients underwent dorsolateral SU with IPG. Post-operative assessment including uroflowmetry and sexual outcomes using IIEF and MSHQ-EJD questionnaires was done at 3 weeks, 3 months, 12 months and half-yearly thereafter. Success was defined by the stable maximum urinary flow value > 14 ml/s or urethral calibration with 16 French Foley catheter. RESULTS: Mean age of patients was 40 years (18-69). The most common aetiology was post-instrumentation (65%) and 60% had stricture at penobulbar site. Mean stricture length was 65 mm. At a mean follow-up of 48 months (range 30-66 months), successful outcomes were seen in 69/80 (87%). Patients with failure were managed with optical internal urethrotomy (OIU). Uroflowmetry and obstructive symptoms significantly improved and sexual function remained unaffected using IPG for SU. CONCLUSIONS: Preputial graft is a tissue familiar to the urologist, located very close to the surgical field, easily harvested and operated under regional anaesthesia. Overall success outcomes are acceptable to BMG urethroplasty.

Primary primitive neuroectodermal tumour of the kidney in adults: Experience of managing 12 cases with systematic review and pooled analysis of literature.

INTRODUCTION: Primitive neuroectodermal tumor (PNET) of the kidney is unusual in adults. These tumours are diagnosed mainly on histopathology and that too sometimes has limitations. With this study, we aimed to review our clinical and histopathological data of patients with renal PNET and reviewing the world literature. METHODS: In this retrospective study, we reviewed our database from January 2006 to July 2018 to include all the cases of primary PNET of the kidney. We also performed systematic literature search to identify all the relevant series on renal PNET. RESULTS: A total of 12 patients including 5 men and 7 women were managed during the above mentioned period. Out of these 7 patients, 2 patients had metastasis at diagnosis, one had locally advanced disease, 6 underwent radical nephrectomy, 5 patients received adjuvant chemotherapy (two currently receiving) and only 1 patient received adjuvant radiotherapy (RT). On Immunohistochemistry (IHC), CD99 and FLI1 were positive in all the patients. Median survival was 10 months. In our review 10 studies were included, 38.6% of the patients had metastatic disease and 10.7% had locally advanced disease at diagnosis. Overall mean survival was 33.75 months. CD99 and FLI1 were positive in 94.3% and 78.5%, respectively. CONCLUSION: PNET remains a pathological diagnosis and IHC has important place in diagnosis of PNET. Locally advanced and metastatic disease is common at diagnosis leading to overall poor survival.

Development and validation of a novel prediction model for predicting renal function recovery after diversion in patients with obstructive uropathy.

OBJECTIVE: To develop and validate a novel prediction model predicting renal function recovery following diversion in patients with obstructive uropathy (OU) to the emergency department (ED). METHODS: After a systematic literature search, a novel prediction model called PGIMER Obstructive Uropathy Score (POUS) was constructed including five variables: age (<60 or >60 years), duration of symptoms (<4 or >4 weeks), presence of solitary functioning kidney, baseline hemoglobin levels and venous blood pH. This model was then validated in a prospective, observational single-center study of patients presenting with OU caused by various etiologies. Patients with OU and raised serum creatinine (>2 mg/dL) presenting to our ED were included. Renal function recovery was defined as creatinine value <1.5 mg/dL at 4 weeks following diversion. RESULTS: In this study, 174 consecutive patients with OU were recruited, and 74 (42.5%) patients had renal function recovery. All the variables included in the POUS were noted to be statistically significant on univariate analysis. On multivariate logistic regression analysis, only POUS was identified as an independent predictor of renal function recovery. On receiver operating curve analysis, the area under the curve for POUS was 0.832 for predicting recovery. A POUS of 5 or more had specificity and sensitivity of 83% and 73.6%, respectively, in predicting renal function recovery. The goodness of fit and calibration plots showed good concordance of the predicted values with the observed values. CONCLUSIONS: The POUS model is an accurate and simple-to-use tool for predicting renal function recovery. POUS model requires external validation prior to clinical use in different populations.

Teleconsultation for paraphimosis reduction in the geriatric population: Lessons from the COVID-19 pandemic.

The health-care sector has been drastically overwhelmed in the wake of prevailing COVID-19 pandemic, hampering elective and emergency medical services alike. The geriatric population is especially affected in this regard as they are the ones who need access to health care services the most, and unfortunately, they are the ones with the highest risk of cross infection and mortality with SARS-COV-2. Lockdown and public restrictions have made the accessibility even harder. Telemedicine has emerged as a useful tool that avoids the risk of cross infection during the face-to-face consultation. Numerous guidelines have been made regarding the implementation of teleconsultations during this pandemic. Through this report, we describe the "beyond guidelines" emergency management of paraphimosis in an aged, bedridden male with comorbidities, through teleconsultation amid the COVID-19 pandemic.

In vitro evidence of NLRP3 inflammasome regulation by histone demethylase LSD2 in renal cancer: a pilot study.

NLRP3 pathway plays a vital role in the pathogenesis of different human cancers but still the regulation of NLRP3 pathway largely unknown. Therefore, we examined the levels of NLRP3 and its downstream components (caspase-1 and IL-1ß) and its relationship with histone modifiers in renal cancer pathogenesis. Total 30 cases of clear cell renal cell carcinoma (ccRCC), were studied for NLRP3, caspase-1 and IL-1ß expression using real-time PCR, which showed the augmented levels of all the three components of NLRP3 inflammasome pathway in ccRCC. Next, role of the FAD dependent monoamine oxidases (LSD2) and jumonji C (JmjC)-domain-containing, iron-dependent dioxygenases (KDM5A) histone demethylases were evaluated in regulation of NLRP3 inflammasome pathway in-vitro using RCC cell line. It was observed that silencing of KDM5A didn't alter the levels of neither of the NLRP3 component but inhibition of LSD2 showed significant effect on NLRP3 expression while no change in caspase-1 and IL-1ß levels. This study suggests that rather LSD2 not KDM5A lysine demethylase family might be involved in the regulation of NLRP3 inflammasome in cancer cells which could be useful for deciphering the future therapeutic targets for the disease.

Spontaneous bilateral extraperitoneal ureteroinguinal herniation.

We describe the clinical and imaging findings of a 53-year-old male who presented with recurrent urinary tract infections with bilateral inguinoscrotal swelling, diagnosed as spontaneous bilateral extraperitoneal ureteroinguinal herniation.

Clinical spectrum, diagnosis, and sexual dysfunction after repair of fracture penis: Is no news good news?

INTRODUCTION: Penile fracture is a rare urological emergency, best managed by early surgical intervention, but the data on subsequent sexual function is sparse. This study was designed to analyze the clinical spectrum and sexual function after penile fracture repair at our tertiary care center. MATERIALS AND METHODS: Ambispective observational study was undertaken from July 2002 to August 2019 which included patients admitted with a history of trauma to the penis in the erect state. The clinical presentation, etiology and the details of the surgical management were noted. Patients were contacted telephonically and were called for follow-up. They were evaluated for the presence of penile nodules or curvature, and the erectile function was objectively recorded using the Sexual Health Inventory for Men (SHIM) questionnaire and the Erection Hardness Score (EHS). RESULTS: Median age at injury was 37 years, and injury during the sexual intercourse (33/43) was the most common etiology. Five patients presented with blood at the meatus. Ultrasound was performed in 27 patients and could detect the injury with a 55% sensitivity. All but one case were repaired through a subcoronal degloving incision. At a median follow-up of 36 months, follow-up data of 20 patients were available. Of the 20 patients, 14 were sexually active. The mean SHIM score was 21.36 ± 1.33 and the mean EHS was 3.21 ± 0.43. Four of the 20 patients developed penile nodule while 2 of them had penile curvature which was not bothersome. CONCLUSION: Penile fracture remains primarily a clinical diagnosis. Although prompt diagnosis and an emergent surgical exploration provides good outcomes in terms of preservation of erectile function, patients should be apprised about the problems of penile nodule and curvature.

The Urological Association of Asia clinical guideline for urinary stone disease.

The Urological Association of Asia, consisting of 25 member associations and one affiliated member since its foundation in 1990, has planned to develop Asian guidelines for all urological fields. The field of stone diseases is the third of its guideline projects. Because of the different climates, and social, economic and ethnic environments, the clinical practice for urinary stone diseases widely varies among the Asian countries. The committee members of the Urological Association of Asia on the clinical guidelines for urinary stone disease carried out a surveillance study to better understand the diversity of the treatment strategy among different regions and subsequent systematic literature review through PubMed and MEDLINE database between 1966 and 2017. Levels of evidence and grades of recommendation for each management were decided according to the relevant strategy. Each clinical question and answer were thoroughly reviewed and discussed by all committee members and their colleagues, with suggestions from expert representatives of the American Urological Association and European Association of Urology. However, we focused on the pragmatic care of patients and our own evidence throughout Asia, which included recent surgical trends, such as miniaturized percutaneous nephrolithotomy and endoscopic combined intrarenal surgery. This guideline covers all fields of stone diseases, from etiology to recurrence prevention. Here, we present a short summary of the first version of the guideline - consisting 43 clinical questions - and overview its key practical issues.

Efficacy of tamsulosin and tadalafil in relieving benign prostatic hyperplasia related symptoms: A randomized double blind placebo controlled cross-over study.

INTRODUCTION: Tadalafil and Tamsulosin have both been approved for use in the management of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). This study compared the differential effects of these two on BPH-LUTS using a cross over study design. METHODS: Men ≥45 years of age, with an International Prostate Symptom Score (IPSS) ≥8 due to BPH-LUTS were included. The patients were randomized into sequence AB (tadalafil 10 mg OD followed by tamsulosin 0.4 mg OD) or BA in a double blind manner. All patients received a placebo lead-in period for 2 weeks, followed by an active drug for 6 weeks; placebo wash out for 4 weeks and then crossed over to second active drug for another 6 weeks. IPSS scores, Uroflowmetry parameters and International Index of Erectile Function-5 scores were recorded. RESULTS: Out of the 40 patients, 36 completed the study. Demographic and baseline characteristics were comparable between the two groups (AB and BA). No significant placebo effects were observed. Tadalafil and tamsulosin significantly improved the total IPSS score and quality of life (P < 0.05) as compared to the baseline. However, there were no significant differences between the two drugs with respect to extent of observed effect and which drug was prescribed 1st in the sequence respectively (P > 0.05). Significant period effect was observed (P < 0.05) i.e., the symptoms did not return to the baseline before the second treatment. Half of the nonresponders to either of the drugs responded when the drug was changed to the other. Tadalafil showed better improvement in EF score as compared to Tamsulosin. CONCLUSION: Both Tadalafil and Tamsulosin improved LUTS and erectile function and those patients who did not respond to Tadalafil showed improvement with Tamsulosin and vice-a-versa.

Efficacy and safety of programmed cell death-1/programmed cell death ligand-1 inhibitors in advanced urothelial malignancy: A systematic review and meta-analysis.

INTRODUCTION: Programmed cell death-1/programmed cell death ligand-1 (PD-1/PDL-1) inhibitors are the newest class of approved drugs for advanced urothelial cancer (AdUC). This review aims to collate the evidence for their efficacy and safety in various treatment settings. METHODS: Extensive search of databases was performed (updated May 2018) and the protocol was registered on PROSPERO (CRD42017081568). The review was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis statement. STATA (v 12) and Revman 5.3.5 were used for data analysis. RESULTS: Ten nonrandomized, open-label clinical trials were included in this review. PD-1/PD-L1 inhibitors were used as second-line, stand-alone in eight trials and as first-line in cisplatin-ineligible in two trials. Heterogeneity was observed for study design, PDL-1 testing methods, cutoff criterias used and translational markers evaluated. The pooled objective response rate (ORR) was 18.2% (95% confidence interval [CI] 15.1-21.2, n = 1785) with PD-1/PDL-1 inhibitors in second-line settings as compared to 12.6% (95% CI 10.3-14.9, n = 736) with second-line chemotherapy and 23.7% (95% CI 19.9-27.4, n = 489) with PD-1/PDL-1 inhibitors as first-line therapy in cisplatin-ineligible patients. The median progression-free survival and overall survival was similar with PD-1/PD-L1 inhibitors in both second- and first-line treatment settings (1.5-2.9 vs. 2.0-2.7 months and 7.9-18.2 vs. 15.9 months) and second-line chemotherapy (3.3-4.0 months and 7.4-8 months). Odds of achieving ORR was 0.10 (95% CI 0.03-0.31, n = 229) in the second-line, stand-alone setting with a combined positive score (CPS) cutoff of 25% and was 0.34 (95% CI 0.19-0.62, n = 265) with a CPS cut-off of 10% in first-line setting in the cisplatin-ineligible. CONCLUSIONS: PD-1/PDL-1 inhibitors appear to be promising in the treatment of AdUC and CPS may be a potentially reliable biomarker for predicting response but needs validation. Caution needs to be exercised until more data are available on imAEs and further studies are required to prove their worth as the standard of care.

Perioperative outcomes of minimally invasive versus open radical cystectomy: A single-center experience.

INTRODUCTION: Open radical cystectomy (RC) is associated with significant morbidity and the role of minimally invasive surgery (MIS) in reducing morbidity of RC is controversial A direct comparison of various surgical modalities on perioperative outcomes is lacking in the Indian literature. We evaluated outcomes of minimally invasive (robotic and laparoscopic) versus open RC with pelvic lymph node dissection (PLND) performed at our institute from 2014 to 2016. METHODS: Eighty-three patients of RC with PLND were prospectively analyzed from December 2014 to February 2016. All patients of muscle invasive urothelial cancer of the bladder undergoing RC (open or MIS) were included in the study. Based on patients preference they were assigned to one of the three groups (Open RC, robot-assisted RC, or laparoscopic RC). Their demographic profile, preoperative disease stage, operative data like operative time, blood loss, intraoperative complications, histopathological data like pathological stage, lymph-node yield etc., postoperative complications if any and total duration of stay were recorded. These data of laparoscopic, open, and robotic cystectomies were compared in terms of various demographic, histopathologic parameters and perioperative outcomes. RESULTS: Twenty-nine patients (34.93%) underwent minimally invasive RC with PLND (5 laparoscopic and 24 robotic). The median age of patients was 58 years. Mean number of lymph nodes removed was 22.5 ± 14.6. The total number of lymph nodes removed in laparoscopic surgery was 104 with a yield of 20.6 per patient, in robotic surgery were 627 with a yield of 26.1 per patient, and in open surgery were 1119 with a yield of 20.7 per patient (P = 0.004). Clavien-Dindo Grade 2 and 3 complications were seen in 37.5% of robotic, 60% of laparoscopic, and 55.54% of open RC. Average blood loss and operative time in laparoscopic, robotic, and open RC were 511.53 ± 311.02 ml, 552.08 ± 267.63 ml, and 512.05 ± 213.9 ml and 8.23 ± 1.36 h (hrs), 7.53 ± 1.92 h, and 5.85 ± 1.76 h, respectively (P = 0.68 and <0.001, respectively). CONCLUSIONS: MIS is associated with significantly longer operative time than open RC. Robotic RC has significantly higher lymph node yield than open or laparoscopic RC. Minimally invasive RC is equivalent to open surgery in terms of perioperative morbidity, mortality, and blood loss.