Prospective Multicenter Evaluation of Pain Before and After Removal of Nonobstructing Renal Calculi: A CoRE Initiative.

PURPOSE: Flank pain associated with stone disease is typically caused by a stone that obstructs urine flow. However, it is plausible that nonobstructing kidney stones may still cause pain. We performed a multicenter, observational trial to evaluate whether treatment of small nonobstructing calyceal stones improves pain and kidney stone-specific health-related quality of life. MATERIALS AND METHODS: Patients aged 18 years or older with nonobstructing renal stone(s) up to 10 mm in longest diameter and moderate to severe pain were recruited. All participants completed 3 questionnaires: the Brief Pain Inventory (BPI), the Patient-Reported Outcomes Measurement Information System pain interference form 6a, and the Wisconsin Stone Quality of Life questionnaire. Thereafter, all participants underwent ureteroscopy for renal stone treatment. All 3 questionnaires were repeated at 2, 6 to 8, and at 12 weeks postprocedure. The primary outcomes were change in preoperative to 12-week postoperative mean BPI score and worst BPI pain score. RESULTS: A total of 43 patients with nonobstructing kidney stones and associated flank pain were recruited. All stones were removed. Preoperatively, BPI scores for mean pain and worst pain were 5.5 and 7.2, respectively which decreased to 1.8 and 2.8 respectively at 12 weeks postoperatively. Wisconsin Stone Quality of Life questionnaire mean score increased from 70.4 to 115.3 at 12 weeks postoperatively. A total of 86% and 69% of patients had at least a 20% and 50% reduction in their mean pain scores, respectively. CONCLUSIONS: This study determined that patients benefit significantly from the removal of calyceal nonobstructing kidney stones for at least 12 weeks with a reduction in pain and an increase in quality of life. Therefore, surgical removal of these stones in this patient population should be offered as a treatment option.

Durability of Response to Primary Chemoablation of Low-Grade Upper Tract Urothelial Carcinoma Using UGN-101, a Mitomycin-Containing Reverse Thermal Gel: OLYMPUS Trial Final Report.

PURPOSE: Our goal was to evaluate long-term safety and durability of response to UGN-101, a mitomycin-containing reverse thermal gel, as primary chemoablative treatment for low-grade upper tract urothelial carcinoma. MATERIALS AND METHODS: In this open-label, single-arm, multicenter, phase 3 trial (NCT02793128), patients ≥18 years of age with primary or recurrent biopsy-proven low-grade upper tract urothelial carcinoma received 6 once-weekly instillations of UGN-101 via retrograde catheter to the renal pelvis and calyces. Those with complete response (defined as negative ureteroscopic evaluation, negative cytology and negative for-cause biopsy) 4-6 weeks after the last instillation were eligible for up to 11 monthly maintenance instillations and were followed for ≥12 months with quarterly evaluation of response durability. Durability of complete response was determined by ureteroscopic evaluation; duration of response was estimated by the Kaplan-Meier method. Treatment-emergent adverse events (TEAEs) were monitored. RESULTS: Of 71 patients who initiated treatment, 41 (58%) had complete response to induction therapy and consented to long-term followup; 23/41 patients (56%) remained in complete response after 12 months (95% CI 40, 72), comprising 6/12 (50%) who did not receive any maintenance instillations and 17/29 (59%) who received ≥1 maintenance instillation. Kaplan-Meier analysis of durability was estimated as 82% (95% CI 66, 91) at 12 months. Ureteric stenosis was the most frequently reported TEAE (31/71, 44%); an increasing number of instillations appeared to be associated with increased incidence of urinary TEAEs. CONCLUSIONS: Durability of response to UGN-101 with or without maintenance treatment is clinically meaningful, offering a kidney-sparing therapeutic alternative for patients with low-grade disease.

Endoscopic management of colovesical and colovaginal fistulas with over-the-scope clips: A single-institution case series.

AIM: Conventional surgical management of colovesical and colovaginal fistulas can be morbid and is contraindicated in many patients. Our aim in this work is to evaluate our experience in the management of colovesical and colovaginal fistulas with endoscopic over-the-scope (OTS) clips. METHOD: A retrospective review of all patients who underwent attempted endoscopic OTS clip management of colovesical and colovaginal fistulas between 2013 and 2020 was performed. Preoperative risk factors, operative details and postoperative outcomes are reported. RESULTS: Ten patients were identified. Fistula types were: colovesical (five), rectovesical (two), colovaginal (two) and rectovaginal (one). The aetiology of the fistula was diverticular disease in seven (70%) cases and surgical complication of pelvic surgery in three (30%). The mean defect age was 157 ± 98 days, the mean defect diameter was 4.5 mm (range 2-10 mm) and the mean fistula length was 15 mm (range 2-25 mm). In nine (90%) cases, fistula identification and cannulation were performed through the nonenteric lumen of the fistula. Initial management with an OTS clip was technically successful in eight (80%) patients. Of the eight patients who underwent OTS clip placement, long-term success (mean follow-up 218 days, range 25-673 days) was achieved after initial intervention in four (50%) patients. One patient underwent serial OTS clip procedures and achieved long-term success after four interventions; three patients have not undergone a repeat procedure after initial failure. CONCLUSION: Endoscopic management of colovesical and colovaginal fistulas with OTS clips offers a promising therapeutic option for patients with contraindications to conventional surgical management. Immediate technical success and long-term success rates are similar to other gastrointestinal tract applications of OTS clips.

Primary chemoablation of low-grade upper tract urothelial carcinoma using UGN-101, a mitomycin-containing reverse thermal gel (OLYMPUS): an open-label, single-arm, phase 3 trial.

BACKGROUND: Most patients with low-grade upper tract urothelial cancer are treated by radical nephroureterectomy. We aimed to assess the safety and activity of a non-surgical treatment using instillation of UGN-101, a mitomycin-containing reverse thermal gel. METHODS: In this open-label, single-arm, phase 3 trial, participants were recruited from 24 academic sites in the USA and Israel. Patients (aged ≥18 years) with primary or recurrent biopsy-proven, low-grade upper tract urothelial cancer (measuring 5-15 mm in maximum diameter) and an Eastern Cooperative Oncology Group performance status score of less than 3 (Karnofsky Performance Status score >40) were registered to receive six instillations of once-weekly UGN-101 (mitomycin 4 mg per mL; dosed according to volume of patient's renal pelvis and calyces, maximum 60 mg per instillation) via retrograde catheter to the renal pelvis and calyces. All patients had a planned primary disease evaluation 4-6 weeks after the completion of initial therapy, in which the primary outcome of complete response was assessed, defined as negative 3-month ureteroscopic evaluation, negative cytology, and negative for-cause biopsy. Activity (complete response, expected to occur in >15% of patients) and safety were assessed by the investigator in all patients who received at least one dose of UGN-101. Data presented are from the data cutoff on May 22, 2019. This study is registered with ClinicalTrials.gov, NCT02793128. FINDINGS: Between April 6, 2017, and Nov 26, 2018, 71 (96%) of 74 enrolled patients received at least one dose of UGN-101. 42 (59%, 95% CI 47-71; p<0·0001) patients had a complete response at the primary disease evaluation visit. The median follow-up for patients with a complete response was 11·0 months (IQR 5·1-12·4). The most frequently reported all-cause adverse events were ureteric stenosis in 31 (44%) of 71 patients, urinary tract infection in 23 (32%), haematuria in 22 (31%), flank pain in 21 (30%), and nausea in 17 (24%). 19 (27%) of 71 patients had study drug-related or procedure-related serious adverse events. No deaths were regarded as related to treatment. INTERPRETATION: Primary chemoablation of low-grade upper tract urothelial cancer with intracavitary UGN-101 results in clinically significant disease eradication and might offer a kidney-sparing treatment alternative for these patients. FUNDING: UroGen Pharma.

Treatment of non-obstructive, non-struvite urolithiasis is effective in treatment of recurrent urinary tract infections.

PURPOSE: To determine if treatment of non-obstructing urolithiasis is effective in management of recurrent UTI. MATERIALS AND METHODS: A retrospective review was performed of patients undergoing elective management of non-struvite upper tract urinary calculi with recurrent UTI from 2009 to 2016. Recurrent UTI was defined at ≥ 3 UTI in 12 months, with symptoms and documented urine culture. Preoperative CT was performed in all patients to determine stone burden. All patients had postoperative imaging and ≥ 12 months of follow-up. Pre- and postoperative variables were between patients who had recurrent UTI after treatment versus those who did not. RESULTS: 46 patients met inclusion criteria. 42 (91.3%) were female. Median age was 63.7 years (IQR 49.1, 73.4) and median total stone burden was 20 mm (IQR 14-35). Within the cohort, 20 (43.5%) underwent ureteroscopy only, 26 (56.5%) underwent PCNL ± URS, and none underwent ESWL. Median postoperative follow-up was 2.9 years (IQR 2.0, 4.3). Only five patients (10.9%) had recurrent UTI after treatment. 80% were with the preoperative pathogen. The presence of residual stone was an independent risk factor for recurrent UTI after treatment (p < 0.046). Diabetes, hypertension, immunosuppression and chronic kidney disease were not. CONCLUSIONS: Stone removal for patients with recurrent UTIs was associated with a high rate of success (89.1%) in elimination of further recurrent UTIs. Residual fragments are independently associated with persistent recurrent UTIs and thus, complete stone removal is of paramount importance in treatment of this patient population.

Intravesical gemcitabine in combination with mitomycin C as salvage treatment in recurrent non-muscle-invasive bladder cancer.

OBJECTIVES: To evaluate oncological outcomes after combination intravesical therapy with gemcitabine (GC) and mitomycin C (MMC) in the setting of recurrent non-muscle-invasive bladder cancer (NMIBC) after failure of previous intravesical therapy. PATIENTS AND METHODS: We retrospectively identified patients with recurrent NMIBC after previous intravesical therapy, who refused or were not candidates for cystectomy, between 2005 and 2011. GC and MMC were sequentially instilled weekly for 6-8 weeks. Data were collected regarding patient demographics, bladder cancer history, and number and type of intravesical therapies before GC/MMC. Outcomes evaluated included time to recurrence and/or progression after GC/MMC. Recurrence-free outcomes were estimated using the Kaplan-Meier method, and Cox proportional hazards regression models were used to test the association of clinicopathological features with outcomes. RESULTS: In all, 27 patients were identified, 23 with high-risk disease (high-grade or carcinoma in situ) and four with intermediate-risk disease (multifocal or recurrent low-grade). All patients received prior intravesical therapy, and 17 patients (63%) received multiple courses. Twenty-four patients were treated with BCG. The median (range) disease-free survival of all patients was 15.2 (1.7-39.3) months. Seventeen patients (63%) developed recurrent bladder cancer, a median of 15.2 months after therapy. One patient progressed to muscle-invasive disease 5 months after treatment, and one developed metastatic disease 22 months after treatment. Three patients went on to cystectomy. Ten patients (37%) had no evidence of disease at last follow-up, with a median follow-up of 22.1 months. CONCLUSION: The combination of intravesical GC and MMC could offer durable recurrence-free survival to some patients with recurrent NMIBC who are not candidates for, or refuse, cystectomy.

Management of a vesicovaginal fistula using holmium laser ablation.

INTRODUCTION AND HYPOTHESIS: The objective was to demonstrate a surgical technique for the management of a small vesicovaginal fistula (VVF) involving a combination of cystoscopic holmium laser ablation and vaginal repair. METHODS: A 55-year-old morbidly obese female presented with complaints of menometrorrhagia and complex adnexal mass. She underwent an attempted robotic hysterectomy, which was converted to open hysterectomy, omentectomy, and lymphadenectomy owing to an intraoperative diagnosis of endometrioid carcinoma of the endometrium and dense pelvic adhesions. Postoperatively, the patient developed intermittent urinary leakage associated with position change. On evaluation, a speculum examination did not reveal any fistulous tract or leakage of fluid in the vagina. A tampon test was positive, but no evidence of a fistula was noted on a CT urogram. Cystourethroscopy was performed and identified a small VVF. The patient subsequently underwent repair of her VVF using a combination of cystoscopic holmium laser ablation and transvaginal excision of the suspected fistula opening. RESULTS: About 2 weeks after the surgery, a tampon test was negative and cystourethroscopy revealed healing bladder mucosa. The patient remains fistula-free at 12 months post-operatively. CONCLUSION: Holmium laser ablation combined with partial vaginal excision may be considered as a management option for a small VVF.

Buckshot colic: utilizing holmium:yag laser for ureteroscopic removal of a bullet fragment within the proximal ureter.

Buckshot colic is a rare phenomenon, presenting as firearm-induced urinary tract obstruction. We present a case of gunshot-induced ureteral obstruction in a 49-year-old male, treated endoscopically with the holmium:YAG (holmium) laser. CT revealed a 1 cm bullet fragment within the left proximal ureter. A percutaneous nephrolithotomy was performed utilizing the holmium laser to fragment the metal into basket-retrievable pieces. At 4 month follow up the patient is without evidence of stricture. To our knowledge, this is the first reported utilization of the holmium laser to treat "buckshot colic". Endoscopy with holmium laser appears a feasible and safe treatment option.

Organ-sparing surgery in urology: partial cystectomy.

PURPOSE OF REVIEW: While radical cystectomy continues to be the gold standard for surgical management of muscle invasive bladder cancer, there has been a renewed interest in partial cystectomy as a viable treatment alternative. The purpose of this review is to summarize and discuss the recent literature regarding partial cystectomy for bladder cancer. RECENT FINDINGS: Utilization of partial cystectomy has remained stable, at a rate of 7-10% of all cystectomies performed nationally. Additionally, recent population-based series as well as single institution cohorts have found that partial cystectomy did not compromise survival when compared to radical cystectomy. While patients may recur, those with organ-confined disease had no difference in survival following salvage cystectomy when compared to primary radical cystectomy. Current data indicate 14% of patients experience an in-hospital complication, which is a marked decrease compared to radical cystectomy. Finally, innovations in surgical technique, such as robotics, as well as the inclusion of partial cystectomy into trimodal therapy, offer exciting new frontiers in bladder cancer treatment. SUMMARY: Once maligned, partial cystectomy now represents a standard-of-care option for management of bladder cancer. Although additional research is needed to clarify patient selection and outcomes, partial cystectomy is an important treatment option for appropriately selected patients.

Thiazide diuretic prophylaxis for kidney stones and the risk of diabetes mellitus.

PURPOSE: Thiazide diuretics used to treat hypertension are associated with a modest risk of diabetes mellitus. It is unknown if there is a similar risk with kidney stone prevention. MATERIALS AND METHODS: We identified and validated incident stone formers in Olmsted County, Minnesota from 1984 to 2011 with manual review of medical records using the Rochester Epidemiology Project. The risk of diabetes mellitus after thiazide therapy was evaluated with and without multivariate adjustment for hypertension, age, gender, race, family history of stones, body mass index and number of stone events. RESULTS: Among 2,350 incident stone formers with a median followup of 10 years, 332 (14%) were treated with thiazide diuretics at some point after the first stone event and 84 (3.6%) received the thiazide diuretic only for kidney stone prevention. Stone formers who received thiazide diuretics were more likely to be older, have hypertension, have higher body mass index and have more stone events. The incidence of diabetes mellitus at 10 years after the first stone event was 9.2% in the group that received thiazide diuretics vs 4.2% in those who did not (HR 2.91; 95% CI 2.02, 4.20). After multivariate adjustment the risk of diabetes mellitus was attenuated (HR 1.20; 95% CI 0.78, 1.83). The risk of diabetes mellitus among those receiving thiazide diuretics solely for kidney stones was further attenuated (multivariate adjusted HR 0.80; 95% CI 0.28, 2.23). CONCLUSIONS: Thiazide diuretic use for kidney stone prophylaxis was not associated with a high risk of diabetes mellitus. Larger studies are needed to determine if there is a modest risk of diabetes mellitus with thiazide diuretics.

Urothelial carcinoma involving the prostate: the association of revised tumour stage and coexistent bladder cancer with survival after radical cystectomy.

OBJECTIVE: To evaluate survival among patients with urothelial carcinoma (UC) within the prostate in order to assess the impact of depth of tumour invasion as well as the importance of a concurrent bladder tumour. PATIENTS AND METHODS: We identified 201 patients who underwent radical cystectomy (RC) between 1980 and 2006 and were found to have UC involving the prostate. All specimens were re-reviewed by a genitourinary pathologist. Survival was estimated using the Kaplan-Meier method and compared with the log-rank test. Cox hazard regression models tested the association of clinicopathological variables with outcome. RESULTS: In all, 93 patients had pTis disease in the prostate, 43 had pT2 tumours, and 66 patients were pT4a. The median follow-up was 10.5 years. The 5-year cancer-specific survival for patients with pTis, pT2, and pT4a prostate UC was 73%, 57%, and 21% respectively (P < 0.001). On multivariable analysis, higher prostate tumour stage (hazard ratio [HR] 2.09; P = 0.01), positive lymph node status (HR 2.09; P = 0.002), and concurrent ≥pT3 bladder cancer (HR 4.16; P < 0.001) were significantly associated with an increased risk of death from UC. CONCLUSIONS: Among patients with prostatic UC involvement, depth of tumour invasion was significantly associated with cancer-specific mortality, validating the staging reclassification. Concurrent locally advanced bladder cancer also negatively impacted survival, suggesting the potential prognostic value of reporting a secondary tumour stage in such cases.

Population-based comparison of laparoscopic and open pyeloplasty in paediatric pelvi-ureteric junction obstruction.

OBJECTIVE: To describe the extent of use and in-hospital outcomes of open and laparoscopic pyeloplasty for paediatric pelvi-ureteric junction (PUJ) obstruction in the USA. PATIENTS AND METHODS: Using the 2004-2008 Nationwide Inpatient Sample, we identified 4590 paediatric patients (≤18 years old) who underwent open or laparoscopic pyeloplasty for PUJ obstruction at 195 hospitals. Multivariable regression models were used to test the associations between hospital and patient covariates (age, gender, race, primary health insurance), type of admission (emergent vs elective), and hospital characteristics (teaching vs non-teaching status; rural vs urban location) with complications, length of stay (LOS), and total hospitalization costs. RESULTS: During the 5-year study interval, 4426 (96.4%) and 164 (3.6%) paediatric patients diagnosed with PUJ obstruction underwent open and laparoscopic pyeloplasty, respectively. The proportion of patients undergoing laparoscopic pyeloplasty gradually increased from 2.4% in 2004 to 4.4% in 2008, but this increase was not significant (P = 0.22 for trend). On multivariable analysis, laparoscopic pyeloplasty was observed to have rates of postoperative complications (2.51 vs 5.00; P = 0.67), LOS (2.42 vs 2.75; P = 0.33) and total hospitalization cost ($9755 vs $8537; P = 0.24) similar to those of open pyeloplasty. CONCLUSIONS: While laparoscopic pyeloplasty was generally an infrequent operation performed for paediatric PUJ obstruction during the period studied, this minimally invasive surgery provided similar outcomes in terms of in-hospital complications, LOS and total hospitalization costs. The results of this study inform policymakers about the comparative effectiveness of laparoscopic and open pyeloplasty.

Synchronous melanosis of upper and lower urinary tract.

Urothelial melanosis is an exceptionally rare diagnosis, with less than 25 cases being reported in the literature. Melanosis of the urothelium is characterized by abnormal melanin deposition within tissues, producing a black, velvety appearance to the urothelial mucosa. We present a 67-year-old male undergoing cystoscopy during a routine percutaneous nephrolithotomy (PCNL), who was found to have diffuse bladder melanosis extending up the ureter and into the renal pelvis. To our knowledge, this is the first reported case of synchronous melanosis of upper and lower urinary tract.

Does partial cystectomy compromise oncologic outcomes for patients with bladder cancer compared to radical cystectomy? A matched case-control analysis.

PURPOSE: To our knowledge long-term oncologic outcomes following partial cystectomy for urothelial carcinoma remain to be defined. We evaluated patterns of recurrence and survival among matched patients treated with partial vs radical cystectomy for bladder cancer. MATERIALS AND METHODS: We identified 86 patients who underwent partial cystectomy for pT1-4N0-1Mx urothelial carcinoma between 1980 and 2006 at our institution. They were matched 1:2 to patients undergoing radical cystectomy based on age, gender, pathological T stage and receipt of neoadjuvant chemotherapy. Survival was estimated using Kaplan-Meier analysis and compared with the log rank test. RESULTS: Median postoperative followup was 6.2 years (range 0 to 27). No difference was noted for 10-year distant recurrence-free survival (61% vs 66%, p = 0.63) or cancer specific survival (58% vs 63%, p = 0.67) between patients treated with partial and radical cystectomy, respectively. Interestingly, 4 of 86 patients (5%) who underwent partial cystectomy showed extravesical pelvic tumor recurrence postoperatively vs 29 of 167 (17%) who underwent radical cystectomy (p = 0.004). In addition, 33 of 86 patients (38%) were diagnosed with intravesical recurrence of tumor after partial cystectomy and 16 of 86 (19%) initially treated with partial cystectomy ultimately underwent radical cystectomy. CONCLUSIONS: Our matched analysis demonstrated no difference in metastasis-free or cancer specific survival between select patients undergoing partial cystectomy and those undergoing radical cystectomy. Nevertheless, patients treated with partial cystectomy remain at risk for intravesical recurrence and, thus, they should be counseled and surveilled accordingly.

Over-the-Counter Alkali Agents to Raise Urine pH and Citrate Excretion: A Prospective Crossover Study in Healthy Adults.

OBJECTIVE: To assess the effect of 2 over-the-counter alkalizing agents on 24 hour urinary parameters. MATERIALS AND METHODS: Ten healthy volunteers without a history of kidney stones were recruited to complete a baseline 24 hour urinalysis with a 4 day diet inventory. Participants then maintained the same diet on either LithoLyte (20 mEq 2 times per day) or KSPtabs (1 tablet 2 times per day) and submitted another 24 hour urinalysis. The process was repeated with the other supplement. Urinary alkali parameters were compared to baseline, and side effects were elicited with a questionnaire. RESULTS: LithoLyte intake resulted in a non-significant increase in citrate (597-758 mg/day, P =.058, an increase in urine pH (6.46-6.66, P =.028), and a decrease in urine ammonium (41-36 mmol/day, P =.005) compared to baseline. KSPtabs resulted in an increase in citrate (597-797 mg/day, P =.037) and urine pH (6.46-6.86, P =.037), with a non-significant decrease in ammonium (41-34 mmol/day, P =.059). No significant differences were seen comparing urinary analytes between LithoLyte and KSPtabs. With Litholyte, no side effects, mild, moderate, and severe side effects were seen in 50%, 40%, 10%, and 0%, respectively. With KSPtabs, rates were 60%, 20%, 10%, and 10%, respectively. CONCLUSION: In healthy participants without a history of kidney stones, LithoLyte and KSPtabs are effective over-the-counter alkali supplements, with a similar side effect profile to prescription potassium citrate.

Topical antiseptic at time of transrectal ultrasound prostate biopsy is associated with fewer severe clinical infections and improves antibiotic stewardship.

BACKGROUND: The 2017 AUA White Paper on prevention of prostate needle biopsy (PNB) complications highlights an algorithm for reducing procedural related infections. The incorporation of topical rectal antiseptic (TRS) at time of transrectal PNB is listed as one such modality. We present data on over 1000 transrectal PNB procedures to determine the impact of TRS on 1) infectious complications and 2) use of augmented procedural antibiotics. METHODS: The records of 1181 transrectal PNB procedures performed over a 10-year period were reviewed. In 2013, TRS with either 10% povidone iodine or 4% chlorhexidine was more regularly incorporated into PNB procedures. Clinical and procedural factors were analyzed for association with post-procedure infections. Infectious complications outcomes were compared in patients receiving TRS (n = 566) versus those who had not (n = 615). RESULTS: A total of 990 men underwent 1181 transrectal PNB procedures. Median age of the cohort was 63 years with a median PSA of 7 ng/dL. Of them, 86% of the men were Caucasian, 28% had undergone at least one prior biopsy, 14% were diabetic, and 6% had prior hospitalization within 6 months of the procedure. Five hundred sixty-six patients (48%) received TRS at time of biopsy. Perioperative IV adjunctive antibiotics were used less frequently in patients receiving TRS (13.4% vs. 28.6%, p < 0.001). Furthermore, patients receiving TRS experienced lower rates of clinical infections (1.2% vs. 2.4%, p = 0.14), as well as lower likelihood of severe infections evidenced by decreased rates of hospital admission (0.5% vs. 2.3%, p = 0.013). Rectal vault bacteriology obtained before and after TRS was available in 180 men noting a 98.1% decrease in colony counts after local treatment. CONCLUSIONS: TRS at time of transrectal PNB was associated with decreased use of IV procedural antibiotics as well as decreased severity of infections post-biopsy. This simple technique enhances antibiotic stewardship while simultaneously improving quality outcomes of the procedure.