Clinical study of steroid receptors in nonmuscle invasive bladder cancer: A domain worth revisiting.

Introduction: The prognostic significance of steroid receptors in bladder cancer remains controversial. This study was designed to determine the expression status of androgen receptor (AR), estrogen receptors (ERα and Erß), and its potential role in predicting survival in patients with nonmuscle invasive bladder cancer (NMIBC). Methods: Sixty patients of NMIBC were screened and 57 (41 males and 16 females) were included in our study. The tissue microarray slides were evaluated by pathologists blinded to the clinical information. Association of distribution of steroid receptors with stage, grade, progression, and recurrence was seen. Results: The mean age of the population was 60.9 ± 9.3 years. Pathologically, majority of the patients were Ta (Ta: T1 stage 61.4% vs. 38.6%). Nine (15.8%) of the tumors stained positive for AR while one (1.8%) tumor stained positive for ERα and 36 (63.2%) tumors stained for ERß. A higher proportion of male NMIBC stained positive for AR (19.5% vs. 6.2%, P = 0.420) while ERß positivity was higher in females (58.5% vs. and 75%,P = 0.247). AR-negative tumors showed higher recurrence (20/48%-42%) as compared to AR-positive tumors (2/9%-22%). ERß-positive tumors showed higher recurrence (15/36%-42% vs. 7/21%-33%, P = 0.179). Progression-free survival (PFS) was found to be significantly lower for ERß-negative group (log-rank test P = 0.035). Conclusion: AR and ERß positivity is found in NMIBC patients while ERα shows minimal staining in NMIBC patients. Although it did not reach a statistical significance, a higher proportion of AR-negative and ERß-positive tumors recurred as compared to AR-positive and ERß-negative patients. PFS was significantly lower in ERß-negative group. Further exploratory studies on larger sample sizes are required to validate these findings in NMIBC patients.

Penile Epithelioid Hemangioendothelioma in a Child.

An 8-year-old boy initially thought to have a penile arteriovenous malformation was later diagnosed with a rare vascular sarcoma, epithelioid hemangioendothelioma (EHE). Despite challenges in diagnosis, he underwent supraselective angioembolization and partial penectomy for oncological clearance. EHE, a low-grade malignancy, requires prompt identification and treatment due to potential systemic involvement.

68Ga-DOTANOC PET/CT in Adrenal Schwannoma.

ABSTRACT: Adrenal schwannoma is a rare adrenal incidentaloma. It is a benign tumor arising from the Schwann cells. Differentiating benign from malignant adrenal lesions requires a combination of clinical, biochemical, imaging, and histopathological findings. 68Ga-DOTANOC PET/CT is one of the sensitive imaging modalities to detect adrenal lesions such as pheochromocytoma. Multiple benign and malignant lesions show somatostatin receptor expression causing a high probability of false-positive findings on somatostatin receptor imaging. We present a case of adrenal incidentaloma positive on 68Ga-DOTANOC PET, which revealed a benign adrenal spindle cell tumor on histopathology.

Transurethral lidocaine (100 mg) bladder irrigation (TULI100) reduces the incidence of catheter related bladder discomfort in transurethral resection of bladder tumors: A randomized, double blind, controlled trial.

BACKGROUND: Transurethral resection of bladder tumors (TURBT) surgeries requires post-resection catheterization for continuous irrigation of the bladder. This indwelling catheter is associated with distressing catheter-related bladder discomfort (CRBD) and increases postoperative pain and agitation. OBJECTIVES: To prove the hypothesis that transurethral 100 mg lidocaine irrigation at the end of TURBT can reduce the frequency of moderate-to-severe postoperative CRBD. METHODS: 116 patients scheduled for TURBT were screened, 94 were recruited and completed the study. American Society of Anesthesiologists Physical Status I-II adult patients, 20-75 years of age undergoing elective TURBT surgery under general anesthesia were included. Transurethral normal saline with 0.01% lidocaine (100 mg in 1 L NS) was used for irrigation 30 min before the completion of surgery in group L, while only normal saline was used for transurethral irrigation in group N. The main outcomes were frequency of CRBD, pain and patient satisfaction at 0, 1, 2, and 6 h postoperatively. RESULTS: A total of 94 patients were analyzed in the study. The incidence of moderate-severe CRBD was significantly lower in group L as compared to group C at 0, 1, and 2 h (65.9% vs. 31.9%, p = 0.01; 31.9% vs. 10.6%, p = 0.012; 21.3% vs. 2.1%, p = 0.004, respectively). At the 6-h mark, the incidence of CRBD was lower in group L, although this did not achieve statistical significance (6.38% vs. 2.1%; p = 0.613). CONCLUSION: Irrigation with 0.01% lidocaine (100 mg) towards the end of TURBT reduces the incidence of moderate-severe CRBD by 52% and increases patient satisfaction.

Current practice patterns in the perioperative management of patients undergoing radical cystectomy: Results from a global survey.

OBJECTIVE: To determine current practice patterns and adherence to various components of enhanced recovery after surgery in cystectomy (ERAC) protocol for peri-operative management of radical cystectomy patients through a global survey. METHODS: A survey containing 25 questions and addressing 15 of the 22 items of the ERAC protocol was developed and disseminated through Email to the urologists with recent bladder cancer publications. The mailing list was generated by retrieving Email-ids of corresponding authors of articles using the keyword "cystectomy" in Scopus from January 2018 to October 2020. RESULTS: The survey was completed by 443 respondents across the globe. About 51.5% of respondents used some form of bowel preparation. A minority used carbohydrate loading (29.8%) and Alvimopan (13.3%). A short duration of nil by mouth was practised by 28.9%. For antibiotic prophylaxis, 51.7% used one, and 42% used two antibiotics. Duration of antibiotics was 24 hours, 48 hours, and >48 hours for 47.6%, 16.9%, and 35.4%, respectively. For peri-operative analgesia, 43.6% used non-steroidal anti-inflammatory drugs, 9.3% opioids and 40.6% combination of both. Pharmacological thrombo-prophylaxis was routinely used by 74.7% respondents. There was significant variability in ERAC and non-ERAC components according to region of practice; The open surgical approach was most commonly used in Africa (92%), whereas it was the robotic approach in North America (or America?) (41%). The use of bowel preparation was higher in Asia (58%) and Africa (65%). Alvimopan use was more common in North America (58%). Most used 1 or 2 prophylactic antibiotics but the duration was shorter (<24 hours) in the Americas and European (58%-83%) compared to Asia and Africa (15%-35%). CONCLUSION: There is high variability in the use of different ERAC components. Other than the timely removal of the abdominal drain and the use of thromboprophylaxis, the overall adherence of ERAC components is low.

External validation of SPARE nephrometery score in predicting overall complications, trifecta and pentafecta outcomes following robot-assisted partial nephrectomy.

BACKGROUND: There is an ongoing need and search for a simple yet accurate nephrometry scoring system for predicting the postoperative outcomes after partial nephrectomy (PN). Simplified PADUA Renal (SPARE) Nephrometry Scoring System, a simplified version of Preoperative Aspects and Dimensions Used for an Anatomical Classification (PADUA) has been proposed as a predictor of postoperative complications following PN recently. However, this score has never been externally validated and assessed as a predictor of trifecta and pentafecta outcomes of PN. In the current study, we applied the SPARE scoring system to our robot-assisted PN cohort (RAPN). METHODS: Prospectively maintained data of patients, who underwent RAPN from November 2014 to December 2018, was abstracted. Imaging was analyzed to calculate SPARE and RENAL nephrometry scores (RNS) by two urologists, independently. SPARE was compared with complications, trifecta outcomes, pentafecta outcomes, and RENAL nephrometry scoring (RNS). RESULTS: Data of 201 RAPN patients were analyzed. The mean SPARE score was 3 (range 0-11). One hundred thirteen patients were classified as low risk, 64 as intermediate risk, and 24 as high risks. On multivariate analysis SPARE score alone predicted complications (OR=1.37, P=0.014) and trifecta outcomes (OR=0.75, P=0.000) while age (OR=0.96, P=0.042), preoperative eGFR (OR=0.97, P=0.001) and SPARE scores (OR=0.81, P=0.016) were predictors for pentafecta outcomes. Receiver operated curve (ROC) analysis between SPARE and RNS in predicting the complications; trifecta and pentafecta outcomes had a comparable area under the curve. CONCLUSIONS: Our study validates the SPARE nephrometry scoring system in predicting postoperative complications, trifecta, and pentafecta outcomes in a RAPN cohort. The predictive accuracy of SPARE is similar to RNS.

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.

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

ABSTRACT 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.

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.

Does Miniaturization Actually Decrease Bleeding After Percutaneous Nephrolithotomy? A Single-Center Randomized Trial.

Introduction: Miniaturization of percutaneous nephrolithotomy (mPCNL) was proposed to decrease postoperative bleeding, as there is decreased parenchymal injury compared with standard percutaneous nephrolithotomy (SPCNL). Published randomized controlled trials (RCTs) evaluating bleeding after mPCNL have shown conflicting results. Hence, the evidence to say that mPCNL offers less postoperative bleeding is not robust. Materials and Methods: Prospective RCT was done by comparing mPCNL and SPCNL for treatment of renal stones of size 1 to 3 cm. Patients with active urinary tract infection, renal malformation, uncorrected coagulopathy, and raised serum creatinine (>1.5 mg/dL) were excluded. Blood loss was evaluated by measuring fall in hemoglobin and hematocrit on postoperative day 1. Postoperative pain was evaluated by visual analogue scale (VAS) score at 6, 24, and 48 hours. Results: A total of 60 patients (30 in each arm) were enrolled during the study period. All the baseline preoperative variables were comparable in both the groups. The SPCNL group had a significantly higher drop in hematocrit level as compared with mPCNL (4.6 ± 3.1% vs 3.1 ± 2.1%, p = 0.02). The mean fall in hemoglobin was higher in SPCNL as compared with mPCNL (1.61 ± 0.9 gm% vs 1.21 ± 0.7 gm%, p = 0.07), but it was not significant. Blood transfusion (BT) rate was comparable in both the groups (one patient in each group). The mPCNL group had significantly less VAS scores at 6 hours (3.27 ± 1.20 vs 4.40 ± 1.52, p = 0.002) and 24 hours (2.10 ± 0.54 vs 2.83 ± 1.05, p = 0.001) after surgery. Postoperative complications and hospital stay were comparable in both the arms. Conclusion: mPCNL is associated with less postoperative bleeding and pain than SPCNL. However, the small tract size does not prevent against the clinically significant bleeding requiring BT.

Prolonged natural history of a cystic renal cell carcinoma: A case report.

We describe the successful management of a 50-year male who presented with gradually progressive abdominal swelling for over 20 years. The highlights of the case are giant renal mass occupying the whole abdomen and the absence of metastasis despite a long history.

Trapped Flexible Ureteroscope in Ureteral Access Sheath During Retrograde Intrarenal Surgery: An Unexpected Problem.

Background: Instrument-related complications occur occasionally with the use of flexible ureteroscopes. In this study, we present a unique problem related to instrument malfunction of flexible ureteroscope during retrograde intrarenal surgery. Case Presentation: A 60-year-old male patient with a 1.2 cm left upper ureteral stone initially underwent semirigid ureteroscopic laser lithotripsy and during the procedure the stone got retropulsed into middle calix of the kidney. Subsequently, a 9.5F (internal diameter) ureteral access sheath was placed and using URF P6R flexible ureteroscope (Olympus) the stone was completely dusted with holmium laser. At the end of the procedure, the operating surgeon was unable to remove the ureteroscope out of the ureteral access sheath as it was getting stuck inside. On careful inspection under fluoroscopy, it was noticed that there was a partial break in the outer surface of the flexible ureteroscope at the level of the junction of the distal flexible part of the ureteroscope with the shaft. Since multiple attempts to retrieve the ureteroscope into the access sheath failed, a decision was made to pull the ureteroscope and ureteral access sheath as a whole over a 0.035″ terumo guidewire. Gentle traction was applied on the entire assembly and the instrument was withdrawn out of ureter over the guidewire under fluoroscopic guidance. A lateral angulation of the distal flexible portion with the shaft of the flexible ureteroscope caused by breakage of the fiber-optic cables led to this problem intraoperatively. Conclusion: Breakage of fiber-optic cables caused by excessive manipulation of flexible ureteroscope during retrograde intrarenal surgery can lead to entrapment of the ureteroscope within the ureteral access sheath. This problem might be solved by gently withdrawing the whole assembly out of the ureter over a guidewire.

Renal cell carcinoma in a pancake kidney: A rare entity.

Pancake kidney is a rare form of renal fusion anomaly. Renal cell carcinoma in such an entity is even rarer and poses a challenge in management due to anomalous vessels. We describe one such patient with an emphasis on successful performance of partial nephrectomy by meticulous planning, with good oncological and functional outcomes.

Primary seminal vesicle adenocarcinoma: A case report of rare entity and discussion of its differential diagnosis using immunohistochemical approach for the core biopsy specimen.

Primary seminal vesicle adenocarcinoma is a rare malignancy of the male genito-urinary system with only a few confirmed reported cases. Initial tissue diagnostic modality is often a core biopsy specimen. Here, we report this rare entity in a 50-year-old male, highlighting the histomorphological and immunohistochemical approach to the core biopsy specimen of the seminal vesicle mass. The patient presented with a history of haematospermia and gross haematuria for one year, and radiological workup was found to have a right seminal vesicle mass. A trans-rectal ultrasound guided core biopsy revealed a tumourous lesion with a predominant papillary architecture and cytological features of neoplasia. Based on positivity for CK7, PAX-8 and CA-125, and Ki-67 index of 30%-40% and negativity for PSA, AMACR, CK20, CDX-2, p63, GATA3, WT1 and calretinin, a diagnosis of primary seminal vesicle adenocarcinoma was offered. The diagnosis was also confirmed on the surgically resected specimen. This case depicts the approach of a pathologist to diagnose this rare entity on the core biopsy specimen and the possible differential diagnoses one must consider.

A brain-permeable inhibitor of the neurodegenerative disease target kynurenine 3-monooxygenase prevents accumulation of neurotoxic metabolites.

Dysregulation of the kynurenine pathway (KP) leads to imbalances in neuroactive metabolites associated with the pathogenesis of several neurodegenerative disorders, including Huntington's disease (HD). Inhibition of the enzyme kynurenine 3-monooxygenase (KMO) in the KP normalises these metabolic imbalances and ameliorates neurodegeneration and related phenotypes in several neurodegenerative disease models. KMO is thus a promising candidate drug target for these disorders, but known inhibitors are not brain permeable. Here, 19 new KMO inhibitors have been identified. One of these (1) is neuroprotective in a Drosophila HD model but is minimally brain penetrant in mice. The prodrug variant (1b) crosses the blood-brain barrier, releases 1 in the brain, thereby lowering levels of 3-hydroxykynurenine, a toxic KP metabolite linked to neurodegeneration. Prodrug 1b will advance development of targeted therapies against multiple neurodegenerative and neuroinflammatory diseases in which KP likely plays a role, including HD, Alzheimer's disease, and Parkinson's disease.