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.

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.

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.

Outcomes of endoscopic management of upper tract urothelial carcinoma.

While radical nephroureterectomy (RNU) remains the gold-standard treatment for upper tract urothelial carcinoma (UTUC), a growing volume of literature surrounding endoscopic, organ-sparing procedures has developed over the past few decades. Based on this, endoscopic management of UTUC has gained acceptance as a standard of care approach, particularly among those with low-risk disease or with imperative indications for organ preservation. As a rare disease, however, data is mostly restricted to retrospective single institution series with relatively small numbers. Therefore, comparative outcomes of endoscopic management to RNU remain incompletely defined. Furthermore, the comparative utility of endoscopic approaches (ureteroscopy versus percutaneous resection) and topical therapy following resection lacks prospective analysis. In this article we review the available literature on endoscopic management of UTUC.

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.

Advances in the management of upper tract urothelial carcinoma: improved endoscopic management through better diagnostics.

As a rare disease, the management of upper tract urothelial carcinoma (UTUC) continues to evolve. While radical nephroureterectomy remains the gold standard, there is a growing desire to pursue nephron-sparing approaches through endoscopic management, particularly for low-risk disease or in the setting of imperative indications. A particular challenge for those undertaking endoscopic management is appropriate grading and staging of tumors, and thereby appropriate patient selection. In this review we will cover the current state of diagnostics for UTUC as well as highlight the challenges in accurate diagnosis. Additionally, we will focus on emerging technologies to aid in optimizing diagnostic accuracy in UTUC. This will include discussion of narrow band imaging, photodynamic diagnosis, optical coherence tomography, and confocal laser endomicroscopy.

Intracavitary therapies for upper tract urothelial carcinoma.

INTRODUCTION: While radical nephroureterectomy remains the gold-standard for upper tract urothelial carcinoma (UTUC), there is a growing push for organ-sparing therapy in low-risk disease. Herein we review the use of intracavitary topical therapy for treatment of UTUC. Areas covered: A PubMed search was performed for studies pertaining to upper tract urothelial carcinoma, with 236 articles reviewed, and distilled for content pertinent to intracavitary therapy for UTUC. Topics discussed include agents used for management of UTUC, most commonly BCG, as well as techniques for administration. Additionally, we review the evidence for curative treatment for Cis versus adjuvant therapy for Ta/T1 disease. Finally, we discuss emerging technologies to improve agent delivery and efficacy in the upper tract. Expert commentary: No significant advances have occurred in topical management of UTUC in the past 2 decades. However, advances in diagnostic techniques such as modern ureteroscopes, and improved diagnostic imaging at the time of ureteroscopy may help improve our patient selection. Additional advances in topical therapy focused on increasing the duration of contact between agent delivered and the upper tract urothelium offer hope that a new leap forward in topical therapy is on the horizon.

Perioperative outcomes of robot-assisted laparoscopic partial cystectomy.

Reports of surgical outcomes after robotic partial cystectomy are limited. The objective of this study is to review surgical outcomes after robotic partial cystectomy at a large tertiary referral center and compare outcomes with patients undergoing open partial cystectomy. Patients undergoing robotic partial cystectomy between 2003 and 2014 were identified. Patients were matched 2:1 based on gender, age, and Charlson Comorbidity Score with patients undergoing open partial cystectomy during the same time period. Patient charts were reviewed for surgical outcomes. Conditional logistic regression adjusted for matching was used to compare outcomes. At our institution, 11 patients underwent robotic partial cystectomy between 2003 and 2014. Median operative time was significantly longer in the robotic group, 214 (IQR 93, 230) minutes, than the open group, 93 (IQR 58, 143) minutes (p = 0.01). There was no difference in median estimated blood loss (p = 0.1). No patient required transfusion. There were no intraoperative complications. Median hospital stay was significantly shorter in the robotic partial cystectomy group, 1 (IQR 1, 2) day, than the open partial cystectomy group, 2 (IQR 2, 4) days (p = 0.01). Median duration of catheterization and complications within 30 days of surgery were not statistically different between the two groups. Median follow-up was 15.5 (IQR 8.6, 19.7) months for the robotic partial cystectomy group and 40.7 (IQR 6.5, 69.4) months for the open partial cystectomy group. Robotic partial cystectomy is safe, effective, and is associated with minimal morbidity when performed in properly selected patients for benign and malignant indications. When compared with open partial cystectomy, robotic partial cystectomy is associated with a longer operative time, but results in a shorter postoperative hospital stay.

Same-Session Bilateral Ureteroscopy: Safety and Outcomes.

OBJECTIVE: To assess the complications and outcomes associated with same-session bilateral ureteroscopy in a tertiary referral center, as same-session bilateral ureteroscopy for stone disease has been critiqued for the theoretical risk of injury to both ureters with subsequent risk to renal function. METHODS: We retrospectively reviewed all cases of bilateral ureteroscopy performed for urolithiasis by a single surgeon at out institution between 2009 and 2014. These were compared to a prospective unilateral ureteroscopy database. RESULTS: There were 117 same-session bilateral ureteroscopic procedures performed in 113 patients totaling 234 ureteroscopies. A flexible ureteroscope was used in 228 ureters (97.4%), and 6 (2.6%) were semirigid only. Ureteral dilators were required in 8 (6.8%) cases. Pre-stenting was performed in 23 (19.6%) patients. Short-term complications were observed following 19 (16.2%) procedures, including 11 (9.4%) Clavien I, 4 (3.4%) Clavien II, and 4 (3.4%) Clavien III. Of the 84 (71.8%) patients who completed a 6-week follow-up, there were no long-term complications. Stone-free rates were 91.4% for patients imaged with abdominal x-ray and ultrasound, and 84.2% for those imaged with computed tomography scans. Neither complications nor re-admissions were significantly different in the unilateral group. Median length of follow-up for the entire cohort was 2.8 years (range 0-7 years). CONCLUSION: Bilateral ureteroscopy can be performed safely with short-term complications, consistent with published literature. We found no long-term complications and high stone-free rates. Bilateral ureteroscopy in a single procedure represents a viable standard of care for patients with bilateral stone disease.

Risk of Hypertension among First-Time Symptomatic Kidney Stone Formers.

BACKGROUND AND OBJECTIVES: Prior work has suggested a higher risk of hypertension in kidney stone formers but lacked disease validation and adjustment for potential confounders. Certain types of stone formers may also be at higher risk of hypertension. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In our study, incident symptomatic stone formers in Olmsted County from 2000 to 2011 were manually validated by chart review and age and sex matched to Olmsted County controls. We followed up patients through November 20, 2015. Hypertension was also validated by manual chart review, and the risk of hypertension in stone formers compared with controls was assessed both univariately and after adjusting for comorbidities. The risk of hypertension among different subtypes of stone formers was also evaluated. RESULTS: Among 3023 coded stone formers from 2000 to 2011, a total of 1515 were validated and matched to 1515 controls (mean age was 45 years old, and 56% were men). After excluding those with baseline hypertension (20% of stone formers and 18% of controls), 154 stone formers and 110 controls developed hypertension. Median follow-up time was 7.8 years in stone formers and 9.6 years in controls. Stone formers were found to have a higher risk of hypertension compared with controls (hazard ratio, 1.50; 95% confidence interval, 1.18 to 1.92), even after adjusting for age, sex, body mass index, serum creatinine, CKD, diabetes, gout, coronary artery disease, dyslipidemia, tobacco use, and alcohol abuse (hazard ratio, 1.58; 95% confidence interval, 1.12 to 2.21). Results were similar after excluding patients who were ever on a thiazide diuretic (hazard ratio, 1.65; 95% confidence interval, 1.16 to 2.38). Stone composition, radiographic stone burden, number of subsequent stone events, and stone removal surgeries were not associated with hypertension (P>0.05 for all). CONCLUSIONS: The risk of hypertension was higher after the first symptomatic kidney stone event. However, kidney stone severity, type, and treatment did not associate with hypertension.

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.

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.

Stone Composition Among First-Time Symptomatic Kidney Stone Formers in the Community.

OBJECTIVE: To determine the variation in kidney stone composition and its association with risk factors and recurrence among first-time stone formers in the general population. PATIENTS AND METHODS: Medical records were manually reviewed and validated for symptomatic kidney stone episodes among Olmsted County, Minnesota, residents from January 1, 1984, through December 31, 2012. Clinical and laboratory characteristics and the risk of symptomatic recurrence were compared between stone compositions. RESULTS: There were 2961 validated first-time symptomatic kidney stone formers. Stone composition analysis was obtained in 1508 (51%) at the first episode. Stone formers were divided into the following mutually exclusive groups: any brushite (0.9%), any struvite (0.9%), any uric acid (4.8%), and majority calcium oxalate (76%) or majority hydroxyapatite (18%). Stone composition varied with clinical characteristics. A multivariable model had a 69% probability of correctly estimating stone composition but assuming calcium oxalate monohydrate stone was correct 65% of the time. Symptomatic recurrence at 10 years was approximately 50% for brushite, struvite, and uric acid but approximately 30% for calcium oxalate and hydroxyapatite stones (P<.001). Recurrence was similar across different proportions of calcium oxalate and hydroxyapatite (P for trend=.10). However, among calcium oxalate stones, 10-year recurrence rate ranged from 38% for 100% calcium oxalate dihydrate to 26% for 100% calcium oxalate monohydrate (P for trend=.007). CONCLUSION: Calcium stones are more common (93.5% of stone formers) than has been previously reported. Although clinical and laboratory factors associate with the stone composition, they are of limited utility for estimating stone composition. Rarer stone compositions are more likely to recur.

Vascular complications after percutaneous nephrolithotomy: 10 years of experience.

OBJECTIVE: To provide a contemporary look at vascular complications after percutaneous nephrolithotomy (PNL) with access performed solely by a urologist using fluoroscopic guidance. METHODS: A retrospective review of 2792 patients who had 3338 PNLs at Indiana University Health Methodist Hospital and Mayo Clinic Rochester was performed. Patients who experienced significant bleeding requiring diagnostic renal angiography and superselective embolization (SSE) were reviewed and compared with the overall database. RESULTS: There were 15 patients (16 renal units) requiring renal angiography and SSE (0.48%). Mean time from PNL to bleeding was 7 days (range, 1-15 days) and to SSE was 9.6 days (range, 2-18 days). Mean drop in hemoglobin was 5.3 g/dL (range, 2-9 g/dL). Transfusion was needed in 9 patients (60%). There were no differences between the vascular complications group and the uneventful PNL group in mean age (55.06 vs 52.2 years; P = .519), UTI history (40% vs 38%; P = .92), mean operative time (125.8 vs 102.47 minutes; P = .192), the need for multiple access (18.75% vs 18%; P = .939), and access location. The vascular complications group had a lower stone burden than the uneventful PNL group (stones > 2 cm; 43.7% vs 74.03%; P = .014). CONCLUSION: The incidence of vascular complications in this contemporary series is one of the lowest reported to date. At our centers, vascular bleeding complications appear to be a random and rare event after PNL as we were unable to identify any specific risk factors. Early SSE avoided the need for blood transfusion in many patients.