Comparison of efficacy of three commonly used alpha-blockers as medical expulsive therapy for distal ureter stones: A systematic review and network meta-analysis

ABSTRACT Introduction: The efficacy of alpha-blockers as medical expulsive therapy (MET) is well established. However, it is not known which of the three most commonly used alpha-blockers (tamsulosin, alfuzosin and silodosin) is the most efficacious. With this study we aimed to assess the efficacy of the three commonly used alpha-blockers as MET for distal ureter stones. Materials and Methods: For this review, we searched multiple databases such as PubMed/Medline, Scopus, Embase, OviD SP, CINAHL, and web of science to identify all the relevant randomized studies comparing the efficacy of tamsulosin, alfuzosin, and silodosin. Preferred reporting items for systematic reviews for network meta-analysis (PRISMA-NMA) were followed while conducting this review and the study protocol was registered with PROSPERO (CRD42020175706). Results: In this review, 31 studies with 7077 patients were included. Compared to placebo all the treatment groups were more effective for both stone expulsion rate (SER) and stone expulsion time (SET). For both SER and SET, silodosin had the highest SUCRA (94.8 and 90.4) values followed by alfuzosin (58.8 and 64.9) and tamsulosin (46.2 and 44.5). The incidence of postural hypotension was similar with all the drugs, whereas, the incidence of retrograde ejaculation was significantly higher for silodosin. Overall confidence for each comparison group in this review ranged from "very low" to "moderate" according to the CINeMA approach. Conclusion: Among the three commonly used alpha-blockers silodosin is the most efficacious drug as MET for lower ureter stones followed by alfuzosin and tamsulosin.

Quality of Life, Efficacy, and Safety of Sequential Intravesical Gemcitabine + Docetaxel versus BCG for Non-Muscle Invasive Urinary Bladder Cancer: A Pilot Study.

PURPOSE: Bacille Calmette-Guerin (BCG) is considered the most effective agent for non-muscle invasive bladder cancer (NMIBC). However, due to BCG-related toxicity, multiple studies have suggested the role of newer chemotherapeutic drugs. The aim of our study was to evaluate intravesical gemcitabine + docetaxel (Gem/Doce) versus BCG with respect to quality of life (QOL), safety, and efficacy in NMIBC. METHODS: A total of 60 patients with NMIBC were evaluated between July 2019 and December 2020 in a prospective manner. The sample size calculation was done, keeping in mind the incidence of intravesical BCG-related complications of up to 50-60% and 20-30% for Gem/Doce combination. The p value of 0.05 was kept as statistically significant. The enrollment ratio was kept at 1, and power of study was aimed at 80%. The study population was alternatively assigned to two groups (BCG vs. Gem/Doce) of 30 patients each. Both the groups received 6 weekly doses of induction therapy followed by 6 monthly doses of maintenance therapy if no recurrence was noted at interim follow-up. QOL scores, safety, and efficacy were assessed at beginning of intravesical therapy, end of induction, and 6 months of maintenance therapy. Cystoscopy examination and cytology were performed at the end of induction therapy and 3-monthly thereafter. RESULT: The preliminary results at the end of 6 months following maintenance therapy showed that the demographic profile, histological stage, and grade were comparable between two groups. The QOL scores using QLQ-30 and QLQ-BLS-24 showed statistically significant differences with the Gem/Doce arm showing better outcomes. There were no progressions to higher stage, while one recurrence each was seen in both groups. Patient-related side effects measured by CTCAE (Common Terminology Criteria for Adverse Events)version 5 showed that the BCG group had higher toxicity profile as compared to Gem/Doce group. CONCLUSION: Gem/Doce combination intravesical therapy is a promising alternative to BCG for treatment of NMIBC, showing better QOL measures and lesser side effects.

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

ABSTRACT 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.

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.

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.

Comparison of efficacy of three commonly used alpha-blockers as medical expulsive therapy for distal ureter stones: A systematic review and network meta-analysis.

INTRODUCTION: The efficacy of alpha-blockers as medical expulsive therapy (MET) is well established. However, it is not known which of the three most commonly used alpha-blockers (tamsulosin, alfuzosin and silodosin) is the most efficacious. With this study we aimed to assess the efficacy of the three commonly used alpha-blockers as MET for distal ureter stones. MATERIALS AND METHODS: For this review, we searched multiple databases such as PubMed/Medline, Scopus, Embase, OviD SP, CINAHL, and web of science to identify all the relevant randomized studies comparing the efficacy of tamsulosin, alfuzosin, and silodosin. Preferred reporting items for systematic reviews for network meta-analysis (PRISMA-NMA) were followed while conducting this review and the study protocol was registered with PROSPERO (CRD42020175706). RESULTS: In this review, 31 studies with 7077 patients were included. Compared to placebo all the treatment groups were more effective for both stone expulsion rate (SER) and stone expulsion time (SET). For both SER and SET, silodosin had the highest SUCRA (94.8 and 90.4) values followed by alfuzosin (58.8 and 64.9) and tamsulosin (46.2 and 44.5). The incidence of postural hypotension was similar with all the drugs, whereas, the incidence of retrograde ejaculation was significantly higher for silodosin. Overall confidence for each comparison group in this review ranged from "very low" to "moderate" according to the CINeMA approach. CONCLUSION: Among the three commonly used alpha-blockers silodosin is the most efficacious drug as MET for lower ureter stones followed by alfuzosin and tamsulosin.

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.

Acute coronary syndrome in young males after a prolonged stay at high altitude.

The Indian population is predisposed to acute coronary syndrome at a younger age, but very few cases are reported at high altitude. Acute coronary syndrome is frequently associated with multiple cardiovascular risk factors. During management of seven young patients with acute coronary syndrome, it was found that none of them had conventional cardiovascular risk factors including recent physical exertion. It is a known fact that the risk of vascular thrombosis increases by 30 times in Indian soldiers after a long stay at high altitude. Therefore, it is necessary to carry out the tests for procoagulant markers to know whether the acute coronary syndrome was because of the prothrombotic state, and if yes, was high altitude responsible for the procoagulant state or whether the person per se had a procoagulant syndrome. With the absence of these tests at hospitals at high-altitude areas, it becomes difficult to ascertain the exact cause of acute coronary syndrome. This study highlights the importance of aggressively testing for procoagulant markers in young patients presenting with chest pain at high altitude, even in the absence of traditional risk factors.

Comparison of efficacy and safety of various management options for large upper ureteric stones a systematic review and network meta-analysis.

To compare the safety and efficacy of various surgical modalities to manage large (> 1 cm) upper ureter stones. Systematic literature search was conducted to include all randomized studies comparing various treatment options for large (> 1 cm) upper ureteric stones. This review included 13 randomized studies with 1871 patients. Laparoscopic ureterolithotomy (LUL) and percutaneous nephrolithotomy (PNL) were superior to ureteroscopy (URS) and shockwave lithotripsy (SWL) for stone-free rates and need for auxiliary treatments. LUL and PNL were equally effective for stone-free rates and the need for auxiliary treatments. According to SUCRA values for stone-free rates and the need for auxiliary treatments, LUL was the best, followed by PNL. For the duration of surgery, there was no significant difference among all the techniques on network analyses, and SWL was the best according to SUCRA values. Length of hospital stay was significantly shorter for URS than LUL and PNL from network analysis, but there was no significant difference for the rest of the comparisons. Overall complications were similar in all the groups. According to the CINeMa approach, the confidence rating ranged from "very low" to "moderate" for various comparisons. LUL followed by PNL is the most efficacious treatment modality for upper ureteric stones compared to SWL and URS in terms of stone-free rates. However, due to the poor quality of included studies, further high-quality randomized studies are needed.

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.

Lipid-rich variant of urothelial carcinoma: a lethal enigma.

Invasive urothelial carcinoma shows marked propensity for divergent differentiation. Several of these 'variant' morphologies have been described in literature and recognised in the 2004 WHO classification. In this report, we detail a case of bladder tumour, diagnosed to be a lipid-rich variant on histopathology after transurethral resection of bladder tumour. Our case encompasses the complete clinical spectrum of this rare and aggressive subtype of urothelial carcinoma starting from initial presentation to postoperative follow-up and recurrence. A keen eye for recognising these variants can ensure a timely diagnosis of these variant and administration of a therapy distinctive from that used in conventional invasive urothelial carcinoma.

IgG4-related Retroperitoneal Fibrosis: An Emerging Masquerader With a Sinister Presentation.

OBJECTIVE: Retroperitoneal fibrosis (RPF) is a rare proliferative fibro-inflammatory disease involving the soft tissues of the retroperitoneum. IgG4 related retroperitoneal fibrosis is an emerging entity which needs to be distinguished from idiopathic RPF. We describe a clinical case of IgG4 related RPF highlighting the importance of clinching this diagnosis. METHODS: A 70 year old female was referred to the outpatient department of our institute with complaints of fatigue, bilateral flank pain and loss of appetite for the past 1 month. The CT and PET scan demonstrated a uniformly enhancing bulky retroperitoneal mass causing bilateral hydroureteronephrosis. The biopsy from the mass lesion revealed IgG4 related disease. The patient was started on corticosteroids after percutaneous nephrostomy placement. RESULTS: Three months post induction of therapy, repeat PET-CT shows resolution of the mass with no FDG avid lesion. Serum IgG4 levels were reduced to normal (27 mg/dL) suggestive of response to treatment. The percutaneous nephrostomies were removed and the patient is doing well on maintenance dose of corticosteroids for her disease. CONCLUSION: The availability of serum IgG4 levels for monitoring treatment response and follow-up can curtail the repeated radiological imaging and associated contrast exposure as compared to idiopathic RPF. Secondly, the diagnosis of IgG4-related RPF shall alert the clinician to look out for extra-retroperitoneal diseases on follow up of this multi-organ disease.