Genomic characterization of metastatic castration-resistant prostate cancer patients undergoing PSMA radioligand therapy: A single-center experience.

BACKGROUND: Genomic defects in DNA-damage repair (DDR) mechanisms have been proposed to affect the radiosensitivity of prostate cancers. In this study, we intended to evaluate the prevalence of genetic alterations in a cohort of metastatic castration-resistant prostate cancer (mCRPC) patients undergoing radioligand therapy (RLT) with prostate-specific membrane antigen (PSMA)-inhibitors as well as the impact of such mutations on treatment outcomes. METHODS: Data of consecutive mCRPC patients from 2017 to 2021 who were treated with PSMA-RLT and underwent next-generation sequencing (NGS) were collected and analyzed for response and survival outcomes. RESULTS: In 95 patients of mCRPC treated with PSMA-RLT, 15 patients (median age: 66 years, range: 50-73 years; [177 Lu]Lu-PSMA-617, n = 12; [225 Ac]Ac-PSMA-617, n = 3) underwent NGS. The median progression-free survival (PFS) of this cohort was 3 months (95% confidence interval: 1.6-4.4 months). On NGS, 21 genetic alterations were reported in 10/15 (67%) patients, of which 13 were DDR-associated alterations involving the genes: ATM (n = 3), BRCA2 (n = 3), TP53 (n = 2), PTEN (n = 2), FANCD2 (n = 1), FANCM (n = 1), and NBN (n = 1). Overall, 5/15 (33%) patients harbored six pathogenic variants (BRCA2, n = 2; ATM, n = 1; TP53, n = 1; PTEN, n = 2). No significant difference was noted for the biochemical response, radiological response, PFS, and overall survival between the patients with and without genetic alterations. CONCLUSIONS: Patients of mCRPC undergoing PSMA-RLT were frequently seen to harbor DDR-associated aberrations, albeit with no significant impact on treatment outcomes. Large prospective trials comparing PSMA-RLT-related outcomes in DDR-deficient and -proficient patients are required to bring out the differences, if any, in a more observable manner.

Utility of WhatsApp in emergency urological practice: An interrater reliability study.

INTRODUCTION: The messaging application 'WhatsApp' is used in clinical practice, often for communication between a medical trainee and a consultant. We designed this study to find the interrater reliability of the data transmitted through this application and validating its use in urological practice. MATERIALS AND METHODS: Clinical details and computerized tomographic (CT) images of 30 patients visiting the urology emergency were posted in a closed WhatsApp group involving three consultants (SKD, APS, and KC). The CT images were posted in the WhatsApp group as Whole Image (WI) and Image of Interest (IOI) format and rated on a scale of 1-5. The consultants formulated a provisional diagnosis and initial management strategy. The interrater reliability of these responses was analyzed in the study. RESULTS: Mean WI rating ranged from 3.03 ± 0.61 to 3.73 ± 0.64 (Cronbach alfa [α]-0.494, P = 0.006). Mean IOI rating ranged from 3.4 ± 0.56 to 4.13 ± 0.73 (α-0.824, P < 0.0001). For diagnosis, the proportion of observed agreement (P0) was 83.3% for SKD and APS, 76.6% for SKD and KC, and 73.3% for APS and KC. For management, P0 was 86.6% for APS and KC, 86.6% for SKD and APS, and 80% for SKD and KC. CONCLUSIONS: WhatsApp Messenger serves to transmit good quality pictures of CT scan images. A reasonable diagnosis and management strategy can be formulated using this app with fair inter-rater reliability.

Autophagy in cancer: Recent advances and future directions.

Autophagy is being explored as a potential therapeutic target for enhancing the cytotoxic effects of chemotherapeutic regimens in various malignancies. Autophagy plays a very important role in cancer pathogenesis. Here, we discuss the updates on the modulation of autophagy via dynamic interactions with different organelles and the exploitation of selective autophagy for exploring therapeutic strategies. We further discuss the role of autophagy inhibitors in cancer preclinical and clinical trials, novel autophagy inhibitors, and challenges likely to be faced by clinicians while inducting autophagy modulators in clinical practice.

Safety and efficacy of bipolar versus monopolar transurethral resection of bladder tumor: a systematic review and meta-analysis.

PURPOSE: Transurethral resection of bladder tumor is the standard of care for the management of patients with bladder mass. Primary objective of this study was to compare safety and efficacy of the two energy modalities used for TURBT (monopolar and bipolar). MATERIALS AND METHODS: Systematic literature search of various electronic databases was conducted to include all the randomized studies comparing two groups. Standard PRISMA (Preferred reporting Items for Systematic reviews and Meta-analysis) guidelines were pursued for this review and study protocol was registered with PROSPERO (CRD42019139987). RESULTS: In the present review, eight RCTs including 1147 patients were included. Resection time, hospital stay and catheter duration were significantly shorter with bipolar group. There was no significant difference in incidence of obturator reflex (OR 0.65, CI [0.35, 1.2], p = 0.17), whereas incidence of bladder perforation was significantly higher in the monopolar group (6.4% versus 3.3%, p = 0.01. However, sensitivity analysis including 3 high quality studies revealed equal incidence of bladder perforations. Need for blood transfusion was similar in the two groups but fall in hemoglobin was significantly lower in bipolar group (MD - 0.45 CI [- 0.72, - 0.18], p = 0.0009). Bipolar group was found to have significantly lower incidence of tissue artifacts due to thermal energy on pathological examination (OR 0.27 CI [0.15, 0.47], p < 0.00001). CONCLUSIONS: Bipolar and monopolar devices are equally safe in terms of obturator jerk and bladder perforation. Bipolar group was significantly better as compared to monopolar for hospital stay, catheter duration and fall in hemoglobin; however, the clinical relevance of most of these parameters is little.

Comparison of efficacy of various drugs used for medical expulsive therapy for distal ureter stones: A systematic review and network meta-analysis.

OBJECTIVES: Medical expulsive therapy has been found to be effective for distal ureteric stones; however, which drug is most efficacious in terms of stone expulsion rate (SER) and stone expulsion time (SET) is not known. With this review we aimed to compare the efficacy of various drug treatments for distal ureter stones used as medical expulsive therapy in terms of SER and SET. METHODS: Systematic literature search was conducted to include all the randomised study comparing various drug interventions for lower ureter stones. Standard preferred reporting items for systematic review and meta-analysis for network meta-analysis (PRISMA-NMA) were pursued. RESULTS: In this review, 50 randomised studies with 12,382 patients were included. For stone expulsion rate (SER), compared with placebo all the treatment groups were more effective except nifedipine and sildenafil. According to the SUCRA values obtained, naftopidil plus steroid was the highest rank and nifedipine lowest. For stone expulsion time (SET), compared with placebo only tadalafil plus silodosin, nifedipine plus steroid, alfuzosin, silodosin, tadalafil and tamsulosin were more effective. SUCRA values were highest for tadalafil plus silodosin and least for naftopidil plus steroid. From subgroup analysis with individual drugs for SER, SUCRA values were highest for naftopidil followed by silodosin and SET was highest for silodosin and least for naftopidil. CONCLUSION: For lower ureter stone, tadalafil plus silodosin is the best combination and silodosin best individual drug considering the SET and SER. Nifedipine as monotherapy is no more effective than control group.

Absence of SARS-CoV-2 infection in the semen of men recovering from COVID-19 infection: An exploratory study and review of literature.

The effect of COVID-19 on the male reproductive tract has been sparsely studied. This exploratory study was designed to determine the presence of SARS-CoV-2 in the semen of men recovering from COVID-19. A systematic literature review was also performed as per PRISMA guidelines to gather perspective on this topic. The prospective study included men 21 years and older recovering from COVID-19 with nasopharyngeal swab negative for SARS-CoV-2 or at least two weeks from the last COVID RT-PCR positivity. After clinical evaluation, freshly ejaculated semen sample by masturbation was collected in a sterile container. Samples were processed for the detection of SARS-CoV-2 by RT-PCR. Twenty-one patients were contacted for the study, 11 of which consented to provide a semen sample. The mean age of the cohort was 29.72 ± 4.52 years. None of the patients gave a history of epididymo-orchitis or sexual dysfunction at the time of assessment. None of the semen samples demonstrated SARS-CoV-2 on RT-PCR. Median duration of semen sample collection from the COVID positivity was 44 days (Range 19-59 days). Detailed literature review revealed that SARS-CoV-2 is not found in patients recovering from COVID-19 infection. We conclude that SARS-CoV-2 is not found in the semen of patients recovering from COVID-19.

Safety and efficacy of "on-demand" tramadol in patients with premature ejaculation: an updated meta-analysis.

INTRODUCTION: Tramadol has been used for the treatment of premature ejaculation, however, the studies published for the same are not well designed. The primary objective of this study was to explore the literature pertaining to the use of tramadol in patients with PE to determine its safety and efficacy in this population. Materials ande methods: Systematic literature search of various electronic databases was conducted to include all the randomized studies and quasi-randomized studies. Standard PRISMA (Preferred reporting Items for Systematic reviews and Meta-analysis) guidelines were pursued for this review and study protocol was registered with PROSPERO (CRD42019123381). RESULTS: Out of 9 studies included in this review, 5 were randomized controlled trials, and rests of the 4 studies were quasi-randomized studies. Tramadol resulted in significantly higher improvement of IELT with the mean difference (MD) of 139.6 seconds and confidence interval (CI) 106.5-172.6 seconds with a p-value of p < 0.00001. All dosages except 25mg fared well as compared to placebo. Tramadol fared better than placebo at 1 month, 2 months, and 3 months after initiation of therapy as compared to the placebo. Tramadol group had reported a significantly higher number of adverse events with treatment as compared to placebo but none of them were serious. CONCLUSION: Tramadol appears to be an effective drug for the management of PE with a low propensity for serious adverse events. However, evidence obtained from this study is of low to moderate quality. Furthermore, effective dose and duration of therapy remain elusive.

Trifecta and pentafecta outcomes following robot-assisted partial nephrectomy for hilar versus nonhilar tumors: A propensity-matched analysis.

INTRODUCTION: Hilar tumors are a unique subset of complex renal masses posing a potential surgical challenge during partial nephrectomy. The outcomes of hilar masses have not been compared to non-hilar renal masses of similar RENAL nephrometry score (RNS). In this study, we analyzed the outcomes of hilar versus nonhilar masses after a propensity score matching. METHODS: Prospectively maintained database of patients who underwent robot assisted PN between November 2014 and December 2018 was abstracted for hilar and nonhilar tumors. We performed propensity matching for baseline variables such as age, sex, body mass index, comorbidities, preoperative glomerular filtration rate, and RNS for each patient on the basis of propensity scores. RESULTS: We included 48 patients with hilar tumors and 153 with nonhilar tumors. On propensity matching, 41 patients were included in each group. The mean operative time (162.4 ± 48.9 min vs. 144.1 ± 38.8 min, P = 0.48), warm ischemia time (29.0 ± 8.8 min vs. 24.4 ± 8.2 min, P = 0.12), and the estimated blood loss (201.8 ± 184.7 ml vs. 150.6 ± 160.5 ml, P = 0.37) were not significantly different between the hilar and the nonhilar groups. Trifecta was achieved in only 14/41 (34.1%) of the patients in the hilar group as compared to 24/41 (58.5%) in the nonhilar group (P = 0.027). Logistic regression analysis identified that hilar location of the tumors was not an independent predictor of overall complications (OR 6.37, confidence interval [CI] 0.5-69.4, P = 0.4), trifecta (OR 0.38, CI 0.14-1.0, P = 0.051), and pentafecta outcomes (OR 0.4, CI 0.1-1.51, P = 0.17). CONCLUSIONS: Hilar location was associated with poorer trifecta outcomes compared to the nonhilar tumors. However, hilar location per se was not an independent predictor of overall complications and trifecta and pentafecta outcomes.

Role of phosphodiesterase inhibitors in stent-related symptoms: a systematic review and meta-analysis.

PURPOSE: Stent-related symptoms are frequent following stent placement for various indications. Use of PDE inhibitors has expanded beyond their classical indication and has been tried in patients with stent-related symptoms. The systematic review was conducted to ascertain the efficacy of PDE inhibitors in ameliorating stent-related symptoms. METHODS: We performed systematic review and metanalysis on the use of PDE inhibitors for stent-related symptoms in patients who underwent stent placement for various reasons (postpercutaneous nephrolithotomy or ureterorenoscopy). We followed PRISMA guidelines while conducting this review and study protocol was registered with PROSPERO (CRD42019121781) RESULTS: Three studies with 280 participants were included in this review. There was considerable heterogeneity across all the outcome parameters assessed; thus, random-effect model was used for analysis. Comparison of PDE inhibitors with control arm revealed that PDE inhibitors were significantly more effective than placebo in all but one domain (Work performance) of the USSQ. On comparison with alfa blockers, PDE inhibitors were found to be equally effective for urinary symptoms, general health, and body pain parameters, but sexual health parameters improved significantly with PDE inhibitors. CONCLUSION: PDE inhibitors can be considered an option for patients with stent-related symptoms especially in patients with sexual dysfunction. Due to various limitations of the studies included in this review, we recommend conducting further high-quality studies.

Phosphodiesterase inhibitors for lower urinary tract symptoms consistent with benign prostatic hyperplasia.

OBJECTIVES: To assess the effects of phosphodiesterase inhibitors (PDEI) compared to placebo and other standard of care drugs i.e alpha blockers (AB) and 5-alpha reductase inhibitors (5-ARI) in men with LUTS consistent with benign prostatic hyperplasia (BPH). METHODS: We conducted a systematic search of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Web of Science, and clinical trials registries of the World Health Organization (WHO) and the National Institutes of Health (NIH) (updated 2 August 2018). Citation tracking and hand-searching of abstracts and conference proceedings was done. We also attempted to contact the study authors in case additional information was needed. Randomised controlled trials (RCT) comparing PDEI versus placebo, AB, or 5-ARI used for at least four weeks in men with BPH-LUTS were included. Three review authors independently screened the literature and extracted data. Primary outcomes were effects on urinary symptoms as assessed by the International Prostate Symptom Score (IPSS-total; score ranging from 0 to 35, with higher values reflecting more symptoms), urinary bother as assessed by the Benign Prostatic Hyperplasia Impact Index (BPHII; score ranging from 0 to 13, with higher values reflecting more bother), and adverse events (AE). We used GRADE to rate the quality of evidence. We considered short-term (up to 12 weeks) and long-term (12 weeks or longer) results separately. RESULTS: We included a total of 16 randomised trials in this review. Primary outcomes: PDEI versus placebo: PDEI may result in a small improvement in IPSS-total score (mean difference (MD) 1.89 lower, 95% confidence interval (CI) 2.27 lower to 1.50 lower; n = 4293; low-quality evidence) compared to placebo, and may reduce the BPHII score slightly (MD 0.52 lower, 95% CI 0.71 lower to 0.33 lower; n = 3646; low-quality evidence). Rates of AEs may be increased (risk ratio (RR) 1.42, 95% CI 1.21 to 1.67; n = 4386; low-quality evidence). This corresponds to 95 more AEs per 1000 participants (95% CI 47 more to 151 more per 1000). Study results were limited to a treatment duration of six to 12 weeks. PDEI versus AB: PDEI and AB probably provide similar improvement in IPSS-total score (MD 0.22 higher, 95% CI 0.49 lower to 0.93 higher; n = 933; moderate-quality evidence) and may have a similar effect on BPHII score (MD 0.03 higher, 95% CI 1.10 lower to 1.16 higher; n = 550; low-quality evidence) and AE (RR 1.35, 95% CI 0.80 to 2.30; n = 936; low-quality evidence). This corresponds to 71 more AEs per 1000 participants (95% CI 41 fewer to 264 more per 1000). Study results were limited to a treatment duration of six to 12 weeks. PDEI and AB versus AB : The combination of PDEI and AB may provide a small improvement in IPSS-total score (MD 2.56 lower, 95% CI 3.92 lower to 1.19 lower; n = 193; low-quality evidence) compared to AB alone. We found no evidence for BPHII scores. AE may be increased (RR 2.81, 95% CI 1.53 to 5.17; n = 194; moderate-quality evidence). This corresponds to 235 more AE per 1000 participants (95% CI 69 more to 542 more per 1000). Study results were limited to treatment duration of four to 12 weeks. PDEI and AB versus PDEI alone: The combination of PDEI and AB may provide a small improvement in IPSS-total (MD 2.4 lower, 95% CI 6.47 lower to 1.67 higher; n = 40; low-quality evidence) compared to PDEI alone. We found no data on BPHII or AE. Study results were limited to a treatment duration of four weeks. PDEI and 5-ARI versus 5-ARI alone: in the short term (up to 12 weeks), the combination of PDEI and 5-ARI probably results in a small improvement in IPSS-total score (MD 1.40 lower, 95% CI 2.24 lower to 0.56 lower; n = 695; moderate-quality evidence) compared to 5-ARI alone. We found no evidence on BPHII scores or AE. In the long term (13 to 26 weeks), the combination of PDEI and 5-ARI likely results in a small reduction in IPSS-total score (MD 1.00 less, 95% CI 1.83 lower to 0.17 lower; n = 695; moderate-quality evidence). We found no evidence about effects on BPHII scores. There may be no difference in rates of AE (RR 1.07, 95% CI 0.84 to 1.36; n = 695; low-quality evidence). This corresponds to 19 more AE per 1000 participants (95% CI 43 fewer to 98 more per 1000). We found no trials comparing other combinations of treatments or comparing different PDEI for BPH-LUTS. CONCLUSIONS: Compared to placebo, PDEI likely leads to a small reduction in IPSS-total and BPHII sores, with a possible increase in AE. There may be no differences between PDEI and AB with regards to improvement in IPSS-total, BPHII, and incidence of AE. There appears to be no added benefit of PDEI combined with AB compared to PDEI or AB or PDEI combined with 5-ARI compared to ARI with regards to urinary symptoms. Most evidence was limited to short-term treatment up to 12 weeks and of moderate or low certainty.

Protocol-based perioperative antimicrobial prophylaxis in urologic surgeries: Feasibility and lessons learned.

INTRODUCTION: Rational use of antibiotics and strict adherence to practice guidelines is essential to prevent antibiotic resistance. The best surgical prophylaxis protocol requires tailoring of the available guidelines in accordance to the local bacterial flora. We designed a protocol for surgical prophylaxis to check the rampant abuse of antibiotics in the department of urology and evaluated its feasibility. MATERIALS AND METHODS: Patients admitted for elective major surgeries under a single unit of our department over a period of 5 months were included in the study. A protocol for antibiotic prophylaxis was designed based on the European Association of Urology guidelines and the local hospital antibiogram. Single-dose intravenous cefuroxime was administered to the patients undergoing clean and clean-contaminated surgeries. Extended protocols were formulated for contaminated surgeries. Postoperative course and complications were recorded. Effectiveness was defined as adherence to the protocol (without an addition or a change in antibiotic regimen) along with an uneventful postoperative course. Prospectively maintained data were analyzed using descriptive statistics. RESULTS: Data of 277 patients were analyzed. The mean age was 48.37 ± 17.39 years and 27.1% had comorbidities. Majority of the surgeries were clean contaminated (81%), and 60.3% of the total were endoscopic. The protocol was effective in 89.5% of the patients (248/277). The failure rate was higher for the contaminated procedures (41.7%) (odds ratio - 6.43; confidence interval = 1.51-27.2, P < 0.001). Post-operative sepsis with or without shock was the commonest cause (16/29, 55.2%) of protocol failure. Fourteen out of the 16 patients who developed sepsis had undergone endourological surgeries. CONCLUSIONS: Protocol-based perioperative antibiotic prophylaxis in urological surgeries is feasible. Similar protocols should be developed and validated at other major centers to limit the unnecessary use of antibiotics and prevent the emergence of antibiotic resistance.

Phosphodiesterase inhibitors for lower urinary tract symptoms consistent with benign prostatic hyperplasia.

BACKGROUND: Benign prostatic hyperplasia (BPH) refers to non-malignant enlargement of the prostate gland that may cause bothersome lower urinary tract symptoms (LUTS). Alpha-blockers (ABs) and 5-alpha reductase inhibitors (5-ARIs) are the mainstay of medical treatment. Recently, phosphodiesterase inhibitors (PDEIs) that so far have been used mainly to treat erectile dysfunction were introduced to treat male LUTS. OBJECTIVES: To assess the effects of PDEIs compared to placebo and other standard of care drugs (ABs and 5-ARIs) in men with LUTS consistent with BPH. SEARCH METHODS: We conducted a systematic search of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Web of Science, and clinical trials registries of the World Health Organization (WHO) and the National Institutes of Health (NIH) (updated 2 August 2018). We performed citation tracking and handsearching of abstracts and conference proceedings. We also contacted study authors to ask for additional information. SELECTION CRITERIA: We considered for inclusion in this systematic review randomised controlled trials (RCTs) comparing PDEIs versus placebo, ABs, or 5-ARIs for at least four weeks in men with BPH-LUTS. DATA COLLECTION AND ANALYSIS: Three review authors independently screened the literature and extracted data. Primary outcomes were effects on urinary symptoms as assessed by the International Prostate Symptom Score (IPSS-total; score ranging from 0 to 35, with higher values reflecting more symptoms), urinary bother as assessed by the Benign Prostatic Hyperplasia Impact Index (BPHII; score ranging from 0 to 13, with higher values reflecting more bother), and adverse events (AEs). We used GRADE to rate the quality of evidence. We considered short-term (up to 12 weeks) and long-term (12 weeks or longer) results separately. MAIN RESULTS: We included a total of 16 randomised trials in this review. The results for primary outcomes are as follows.PDEI versus placebo: PDEIs may result in a small improvement in IPSS-total score (mean difference (MD) 1.89 lower, 95% confidence interval (CI) 2.27 lower to 1.50 lower; n = 4293; low-quality evidence) compared to placebo, and may reduce the BPHII score slightly (MD 0.52 lower, 95% CI 0.71 lower to 0.33 lower; n = 3646; low-quality evidence). Rates of AEs may be increased (risk ratio (RR) 1.42, 95% CI 1.21 to 1.67; n = 4386; low-quality evidence). This corresponds to 95 more AEs per 1000 participants (95% CI 47 more to 151 more per 1000). Study results were limited to a treatment duration of six to 12 weeks.PDEI versus AB: PDEIs and ABs probably provide similar improvement in IPSS-total score (MD 0.22 higher, 95% CI 0.49 lower to 0.93 higher; n = 933; moderate-quality evidence) and may have a similar effect on BPHII score (MD 0.03 higher, 95% CI 1.10 lower to 1.16 higher; n = 550; low-quality evidence) and AEs (RR 1.35, 95% CI 0.80 to 2.30; n = 936; low-quality evidence). This corresponds to 71 more AEs per 1000 participants (95% CI 41 fewer to 264 more per 1000). Study results were limited to a treatment duration of six to 12 weeks.PDEI and AB versus AB alone: the combination of PDEI and AB may provide a small improvement in IPSS-total score (MD 2.56 lower, 95% CI 3.92 lower to 1.19 lower; n = 193; low-quality evidence) compared to AB alone. We found no evidence for BPHII scores. AEs may be increased (RR 2.81, 95% CI 1.53 to 5.17; n = 194; moderate-quality evidence). This corresponds to 235 more AEs per 1000 participants (95% CI 69 more to 542 more per 1000). Study results were limited to treatment duration of four to 12 weeks.PDEI and AB versus PDEI alone: the combination of PDEI and AB may provide a small improvement in IPSS-total (MD 2.4 lower, 95% CI 6.47 lower to 1.67 higher; n = 40; low-quality evidence) compared to PDEI alone. We found no data on BPHII or AEs. Study results were limited to a treatment duration of four weeks.PDEI and 5-ARI versus 5-ARI alone: in the short term (up to 12 weeks), the combination of PDEI and 5-ARI probably results in a small improvement in IPSS-total score (MD 1.40 lower, 95% CI 2.24 lower to 0.56 lower; n = 695; moderate-quality evidence) compared to 5-ARI alone. We found no evidence on BPHII scores or AEs. In the long term (13 to 26 weeks), the combination of PDEI and 5-ARI likely results in a small reduction in IPSS-total score (MD 1.00 less, 95% CI 1.83 lower to 0.17 lower; n = 695; moderate-quality evidence). We found no evidence about effects on BPHII scores. There may be no difference in rates of AEs (RR 1.07, 95% CI 0.84 to 1.36; n = 695; low-quality evidence). This corresponds to 19 more AEs per 1000 participants (95% CI 43 fewer to 98 more per 1000).We found no trials comparing other combinations of treatments or comparing different PDEI agents. AUTHORS' CONCLUSIONS: Compared to placebo, PDEI likely leads to a small reduction in IPSS-total and BPHII sores, with a possible increase in AEs. There may be no differences between PDEI and AB with regards to improvement in IPSS-total, BPHII, and incidence of AEs. There appears to be no added benefit of PDEI combined with AB compared to PDEI or AB alone or PDEI combined with 5-ARI compared to ARI alone with regards to urinary symptoms. Most evidence was limited to short-term treatment up to 12 weeks and of moderate or low certainty.

STAMPEDEing metastatic prostate cancer: CHAARTing the LATITUDEs.

With the emergence of recent landmark trials, the treatment for hormone-sensitive metastatic prostate cancer (hsMPC) is changing from androgen deprivation therapy (ADT) alone to combination therapy. Both, docetaxel chemotherapy and abiraterone in addition to ADT have been extensively studied in well-conducted randomized controlled trials and were shown to improve outcomes. However, this paradigm shift in the treatment has also raised some queries. This mini review reflects upon the four landmark trials and tries to provide some perspective about the decision-making process for the patients with hsMPC.

Comparison of RENAL, PADUA, and C-index scoring systems in predicting perioperative outcomes after nephron sparing surgery.

INTRODUCTION AND OBJECTIVE: The RENAL, PADUA and centrality index (C-index) nephrometry scoring systems (SS) have been individually evaluated for their role in predicting trifecta outcomes after nephron-sparing surgery (NSS). However, there is little data on their comparative superiority. The present study was designed to evaluate the predictive value of three SS and to assess interobserver reliability. MATERIALS AND METHODS: Fifty patients undergoing NSS at our center between January 2014 and April 2016 were included in the study. The demographic details were noted. Images (computed tomography [CT] scans or magnetic resonance imaging) were reviewed by a urologist and a radiologist independently and RENAL, PADUA, and C-index were calculated. The correlation between these scoring system and trifecta outcomes were calculated. RESULTS: The RENAL and PADUA score did not correlate with any of the perioperative parameters. However, C-index had a significant correlation with operative time (OT) (P = 0.02) and trifecta outcomes (P < 0.05). There was an excellent concordance between the two observers in scoring the RENAL score (α = 0.915; intraclass correlation coefficient [ICC] = 0.814) and PADUA score (α = 0.816; ICC = 0.689 [P < 0.001]). There was lesser although acceptable concordance in the calculation of C-index (ICC -0.552; α -0.711). CONCLUSIONS: There is good correlation among all the 3 SS. C-index has lower reproducibility due to difficult mathematical calculation but correlated best with trifecta outcomes.

Functional inhibition of Hsp70 by Pifithrin-µ switches Gambogic acid induced caspase dependent cell death to caspase independent cell death in human bladder cancer cells.

Heat shock protein-70kDa (Hsp70) is a member of molecular chaperone family, involved in the proper folding of various proteins. Hsp70 is important for tumor cell survival and is also reported to be involved in enhancing the drug resistance of various cancer types. Hsp70 controls apoptosis both upstream and downstream of the mitochondria by regulating the mitochondrial membrane permeabilization (MMP) and apoptosome formation respectively. In the present study, we have elucidated the role of Hsp70 in Gambogic acid (GA) induced apoptosis in bladder cancer cells. We observed that functional inhibition of Hsp70 by Pifithrin-µ switches GA induced caspase dependent (apoptotic) cell death to caspase independent cell death. However, this cell death was not essentially necrotic in nature, as shown by the observations like intact plasma membranes, cytochrome-c release and no significant effect on nuclear condensation/fragmentation. Inhibition of Hsp70 by Pifithrin-µ shows differential effect on MMP. GA induced MMP and cytochrome-c release was inhibited by Pifithrin-µ at 12h but enhanced at 24h. Pifithrin-µ also reverted back GA inhibited autophagy which resulted in the degradation of accumulated ubiquitinated proteins. Our results demonstrate that Hsp70 plays an important role in GA induced apoptosis by regulating caspase activation. Therefore, inhibition of Hsp70 may hamper with the caspase dependent apoptotic pathways induced by most anti-cancer drugs and reduce their efficacy. However, the combination therapy with Pifithrin-µ may be particularly useful in targeting apoptotic resistant cancer cells as Pifithrin-µ may initiate alternative cell death program in these resistant cells.

Robot-assisted vesicovaginal fistula repair: a safe and feasible technique.

INTRODUCTION AND HYPOTHESIS: Open transabdominal repair of vesicovaginal fistula (VVF) requires a long cystotomy incision, suprapubic drainage and delayed recovery. Laparoscopic repair is limited by difficult suturing in pelvic procedures. Therefore, the utility of robotic assistance is being increasingly explored. We share our initial experience of robot-assisted laparoscopic VVF repair. METHODS: The data from patients who underwent robot-assisted VVF repair from December 2014 to August 2016 were recorded and analyzed. Patients underwent standard preoperative evaluation. After cystovaginoscopy and placement of an access catheter across the fistula, a four-port transperitoneal approach was used. Following adhesiolysis, limited posterior cystotomy was performed. The vaginal and bladder flaps were separated and repaired in the transverse and vertical directions, respectively. V-Loc sutures were used for bladder closure. Omental/sigmoid colon epiploicae or a peritoneal flap was interposed. A pelvic drain was placed. RESULTS: During the study period, 30 patients underwent surgery, of whom 11 (36.7 %) had complex VVF (9 with failure of a previous repair, 1 following radiotherapy, and 1 with a large defect following obstructed labor), and 27 had supratrigonal VVF. The mean age of the patients was 43.5 ± 8.6 years. The mean operative time was 133 ± 48 min. Median blood loss was 50 ml (IQR 50 ml). No suprapubic catheter was placed. The median durations of drain placement and hospital stay were 3 days (IQR 2 days) and 7.5 days (IQR 4.5 days), respectively. The median duration of follow up was 38 weeks (IQR 46 weeks). No recurrence was seen in 28 patients (93.3 %). CONCLUSIONS: Current data suggest that robot-assisted VVF repair is safe and feasible and probides the advantages of minimally invasive surgery.

PREVALENCE AND PREDICTORS OF PRIMARY HYPERPARATHYROIDISM AMONG PATIENTS WITH UROLITHIASIS.

OBJECTIVE: Urolithiasis may be the only presenting manifestation of primary hyperparathyroidism (PHPT), and early detection of PHPT in such patients may prevent future urolithiasis and other PHPT complications. This study was performed to study the prevalence and predictors of PHPT in patients presenting with urolithiasis. METHODS: Consecutive patients presenting with urolithiasis were evaluated for clinical and biochemical manifestations of PHPT with serum and urine calcium (Ca), serum intact parathyroid hormone and 25 (OH) vitamin D. We then compared the clinical and biochemical characteristics of PHPT patients presenting with urolithiasis (group A) and without (group B). RESULTS: During the 3-year study period, 381 patients with urolithiasis were seen with a mean age of 38.5 ± 13.9 years. Nineteen of the 381 (5%) patients had histologically proven PHPT (group A). Four patients in group A (21%) and 8 in group B (2%) had nephrocalcinosis (P<.0001), multiple stones (≥3), calcific pancreatitis, and neuropsychiatric manifestations were more common in group A (P<.0001). Presence of multiple or bilateral stones, and recurrent stone episodes predicted PHPT (odds ratio [OR]: 3.06, confidence interval [CI]: 0.87, 0.7). CONCLUSION: One out of every 20 patients with urolithiasis had PHPT, which is higher than the prevalence of PHPT in general population. The presence of nephrocalcinosis and multiple, bilateral, and recurrent stone disease increased the risk of PHPT among stone formers. ABBREVIATIONS: Ca = calcium; CI = confidence interval; iPTH = intact parathyroid hormone; nPHPT = normocalcemic PHPT; OR = odds ratio; PHPT = primary hyperparathyroidism.

Initial experience of robotic nephron sparing surgery in cases of high renal nephrometry scores.

INTRODUCTION: The renal nephrometry scoring (RNS) system enables prediction the feasibility of nephron-sparing surgery (NSS) in renal masses. There is insufficient data regarding the outcome of robot-assisted NSS in tumors with RNS ≥10. We reviewed the trifecta outcomes of patients undergoing robotic NSS with high RNS and compare it with tumors of low and intermediate RNS. MATERIALS AND METHODS: Our prospectively maintained data of all robot-assisted NSS were reviewed, and those with RNS of ≥10 were identified. Patient data, outcomes and postoperative estimated glomerular filtration rate were compared between high, intermediate and low RNS patients. RESULTS: In high RNS group, the mean age of the patients was 53 years (male:female = 15:3). Mean diameter of tumors was 6.28 cm (3.0-10.5 cm). Mean operative time was 173.61 ± 52.66 min and mean warm ischemia time was 27.85 ± 5.27 min. Mean estimated blood loss (EBL) was 363.89 ± 296.45 ml. Mean hospital length of stay was 5.39 ± 1.91 days (3-9 days). When compared with low and intermediate RNS, only EBL and need for pelvicalyceal system repair was significantly higher in high RNS group. Postoperative complications, renal function preservation and oncological outcomes at 3 months were comparable in all the three groups. CONCLUSION: Robot-assisted NSS is feasible with comparable outcomes in tumors with high RNS.

Plateau pattern of detrusor contraction: A surrogate indicator of presence of external sphincter dysfunction during micturitional phase of urodynamic study.

INTRODUCTION: Dysfunctional voiding results from a disturbance in the coordination between sphincter relaxation and detrusor contraction. Video urodynamic studies with electromyography (EMG) are used for diagnosis but have limitations of availability and interpretation. We identified a plateau type voiding detrusor pressure tracing pattern in these patients with a potential of helping diagnosis. MATERIALS AND METHODS: Urodynamic data and tracings of adult patients having been diagnosed with external urethral sphincter dysfunction (EUSD) were retrospectively analyzed. The urodynamic studies comprised of pressure flow studies, micturitional urethral pressure profilometry, and voiding cystourethrogram (VCUG). Diagnosis of EUSD was based on the presence of intermittent or continuous narrowing in the region of EUS on VCUG along with a urethral-vesical pressure gradient of >20 cm H2O in males and >5 cm H2O in females. RESULTS: A total of 25 patients (14 men and 11 women) with a mean age 36.6 ± 16.5 years, presented with lower urinary tract symptoms (international prostate symptom score 18 ± 5) and were diagnosed with EUSD on urodynamics/cystourethrography. The cause of EUSD was neurogenic DESD in four, dysfunctional voiding in 20 and voluntary pelvic floor squeeze in one. Resting maximum urethral closure pressure at EUS was 142.2 ± 38.3 cmH2O in both sexes. Three patients had detrusor overactivity. EMG activity during voiding was high in 10 patients, low in three, inconclusive in seven, and not performed in three. A plateau type pattern of detrusor contraction was observed in all the patients. This was qualitatively different from the roughly bell-shaped curve of detrusor contraction in men with prostatic obstruction (n = 14) and women with stress urinary incontinence (n = 11). CONCLUSIONS: Patients with EUSD have a characteristic plateau pattern of detrusor contraction on urodynamics which can be used as a surrogate for urodynamic diagnosis of nonrelaxing EUSD.

Instrument malfunction during robotic surgery: A case report.

Robotic assistance is the new dimension of minimally invasive surgery. Despite being the state-of-the-art technology, newer technical problems still occur during robotic surgeries which are not addressed in the trouble shooting manual. We report one such problem being encountered with the tip cover accessory of monopolar scissors. In the current report, we discuss the technical fault and its correction. We feel that this problem needs to be registered into the trouble-shooting manual to prevent such incidents in future.