High ambient temperature impact on the pattern of emergency-room visits due to renal colic in the Middle East.

Urolithiasis has a seasonal pattern, with an established increase in incidence during the summer months. This study aims to assess the impact of high ambient temperatures on emergency room (ER) visits related to renal colic (RC) in a Middle Eastern country over the past decade. Population data were extracted using the MDClone Big Data platform. We recorded demographic and clinical data on all RC-associated ER visits from January 2012 to April 2023 and calculated the heat index (HI) that combines daily average coastal plane temperatures and humidity percentages. There was a total of 12,770 ER visits (median age 48 years, 9,236 (72%) males). The number of visits increased during the hottest months (July-October), with the highest numbers recorded during August. The number of visits remained stable throughout the study. We identified a linear association between humidity and the incidence of ER visits (p = 0.002), and a non-linear association between ambient temperature (p < 0.0001) and HI (p < 0.0001). There was a direct relationship between high temperatures and ER visits on the same day (risk ratio [RR]: 1.75, p = 0.036), with a 2-day lag (RR: 1.123, p = 0.024). In Conclusion, there is a significant relationship between temperature, humidity, HI, and the number of ER visits due to RC. Adjusted resource allocation and healthcare workforce availability are essential for managing additional cases during heat waves. Clinical implications: Increased demand is expected during heatwaves and within a 2-day lag, emphasizing the importance of proactive strategies to effectively manage RC patients.

Do Urine Cytology and FISH Analysis Have a Role in the Follow-Up Protocol of Upper Tract Urothelial Carcinoma?

BACKGROUND: Current guidelines recommend a stringent follow-up regimen that includes interval cystoureteronephscopy, CT urography, and selective urine cytology sampling for upper tract urothelial carcinoma (UTUC) patients undergoing endoscopic treatment and management. There are no recommendations regarding FISH analysis. Our purpose was to assess the efficacy of cytology and FISH as part of the follow-up protocol and its significance to clinical decision-making in this scenario. METHODS: The medical records of all patients who managed endoscopically for UTUC at our institute between 2014 and 2022 were retrospectively analyzed. Demographic and clinical data, histology, cytology, and FISH results were collected. FISH analysis was considered malignant according to Paris criteria. RESULTS: During the study period, 62 patients underwent 561 ureteroscopies as part of the treatment and follow-up regimen of low-grade UTUC. Urine from the affected upper tract was sampled for cytology in 377 procedures, and FISH analyses were performed in 273. In 75.4% of FISH analyses, the result was different from the cytology results: FISH found malignant aberrations in 15.5% of cases where cytology was benign. Furthermore, FISH classified all the cells defined as atypical via cytology as either benign or malignant. In only one case (0.17%), the urinary cytology report changed the follow-up regimen. CONCLUSION: Cytology may be omitted from the follow-up protocol of low-grade UTUC. In the handful of cases cytology does assist the diagnosis of UTUC, there is an additional benefit to performing FISH analysis, particularly when cellular atypia is reported in the cytology results.

Unveiling the Challenges in Tandem Ureteral Stent Management for Malignant Ureteral Obstruction: Failure Rate, Risk Factors, and Durability of Their Replacement.

BACKGROUND: Malignant ureteral obstruction (MUO) is a sequela of advanced malignant disease that requires renal drainage, with tandem ureteral stents (TUSs) being a viable option. This study aimed to evaluate the TUS failure rate, associated risk factors, and the feasibility of replacing failed TUSs with a new pair of stents. METHODS: A retrospective analysis of MUO patients treated with TUS insertion from 2014 to 2022 was conducted. TUS failure was defined as urosepsis, recurrent urinary tract infections, acute kidney failure, or new hydronephrosis on imaging. Cox proportional hazard regression analysis identified the independent predictors of TUS failure. RESULTS: A total of 240 procedures were performed on 186 patients, with TUS drainage failing in 67 patients (36%). The median time to failure was 7 months. Multivariate analysis revealed female gender (OR = 3.46, p = 0.002), pelvic mass (OR = 1.75, p = 0.001), and distal ureteral obstruction (OR = 2.27, p = 0.04) as significant risk factors for TUS failure. Of the failure group, 42 patients (22.6%) underwent TUS replacement for a new pair. Yet, 24 (57.2%) experienced a second failure, with a median time of 4.5 months. The risk factors for TUS second failure included a stricture longer than 30 mm (OR = 11.8, p = 0.04), replacement with TUSs of the same diameter (OR = 43, p = 0.003), and initial TUS failure within 6 months (OR = 19.2, p = 0.006). CONCLUSIONS: TUS insertion for the treatment of MUO is feasible and has good outcomes with a relatively low failure rate. Primary pelvic mass and distal ureteral obstruction pose higher risks for TUS failure. Replacing failed TUSs with a new pair has a success rate of 42.8%. Consideration should be given to placing larger diameter stents when replacing failed TUS.

Strategies of Endoscopic Management of Upper Tract Urothelial Carcinoma among Endourologists: A Global Survey.

Up-to-date guidelines on the management of upper tract urothelial carcinoma (UTUC) are continuously published. We aim to assess the variability of diagnosis and treatment strategies in the endoscopic management of UTUC and adherence to European Association of Urology and National Comprehensive Cancer Network guidelines. A 15-question survey was designed to query practitioners on approaches to clinical practice and knowledge about endoscopic treatment indications and techniques. It was emailed to all members of the Endourologic Society through the society's office, and to all Israeli non-member endourologists. Eighty-eight urologists participated in the survey. Adherence to guidelines on indications for endoscopic management was only 51%. Most of the survey respondents (87.5%) use holmium laser for tumor ablation, and ~50% use forceps for biopsy while the other half use baskets. Only 50% stated that they would use Jelmyto® for specific indications. Most (80%) indicated that they repeat the ureteroscopy 3 months after the first one, and 52.3% continue with follow-up ureteroscopy every 3 months during the first year after diagnosis. There is vast variability among endourologists in the technical aspects of UTUC, the indications for endoscopic management, and adherence to the available guidelines for managing UTUC.

Quality of life with tandem ureteral stents compared to percutaneous nephrostomy for malignant ureteral obstruction.

PURPOSE: Malignant ureteral obstruction (MUO) is treated with kidney decompression by a percutaneous nephrostomy (PCN) or internal ureteral stents. The objective of this study was to compare quality of life (QoL) with a PCN compared to tandem ureteral stents (TUS) in cases of MUO. METHODS: We reviewed the medical records of patients with MUO who were treated by PCN/TUS in our institution between June 2019 and May 2020. Patients were asked to fill out a QoL questionnaire, a tube-symptoms questionnaire, report a general health scale, and asked for a drain preference if they had experience with both drains. Scores of both groups were compared and predictors of all QoL and tube-symptoms measures were searched using multivariate analysis. RESULTS: Seventy-four patients with a PCN and 30 with TUS were included in the study. No statistically significant difference was found in all QoL and tube-symptoms measurements between the two drains. Type of drain was not found to be a predictor of QoL or tube-related symptoms. Eighty-four percent of patients (11/13) who have experience with both types of drains preferred TUS. CONCLUSION: TUS and PCN for relief of MUO have a negative and similar effect on various areas of QoL and urinary symptoms. Most patients who had experience with both types of drains preferred TUS over PCN. In this patient population with a grim prognosis, this negative effect must be communicated to patients, and calculated against the potential benefits of drainage.

Changing Trends in Surgical Management of Nephrolithiasis among Young Adults: A 15-Year Population-Based Study.

Background: Increases in obesity and diabetes rates among all ages have led to a greater prevalence of nephrolithiasis worldwide. We aimed to explore the changing trends in surgical management of nephrolithiasis in young adults over a 15 year period. Methods: We reviewed medical records of military personnel for information on the diagnosis and care of nephrolithiasis before and during active service between 2007−2021, divided into three 5 year periods: 2007−2011, 2012−2016, and 2017−2021. Demographic, clinical, radiological, and surgical data were retrieved for the analysis of changing trends. Results: The records of 1,117,692 recruits yielded 7383 (0.66%) with stone-related surgeries, of whom 1885 were operated during military service. Their median age was 19.6 years (interquartile range [IQR] 16.8−21.2), 829 (70%) were males, and the cohort's median body mass index was 23.6 (IQR 17.3−26.1). There was a dramatic decline in shock wave lithotripsy (SWL) prevalence (35.1%, 10.4%, and 4.4%, respectively) with a continually increasing prevalence of ureteroscopy (URS)/retrograde intrarenal surgery (RIRS) (62.7%, 88.5%, and 94.6%, p = 0.01). Percutaneous nephrolithotomy (PCNL) procedures have become nearly extinct over time (0.8% in 2017−2021). The number of median-sized stones treated by URS/RIRS increased (7.5 mm, 8.2 mm, and 9.7 mm, p = 0.044), but not those treated by SWL/PCNL. The median length of medical leave for URS/RIRS and PCNL decreased significantly (7 vs. 4 days, p = 0.05 and 10 vs. 6 days, p = 0.036, respectively), with no comparable change for SWL. There was a substantial decline in ancillary procedures in the URS/RIRS groups (9%, 6.8%, and 3.1%, p < 0.01), but not in the SWL/PCNL groups. Conclusions: Advancements in technology and surgical training are leading to the extinction of SWL and the adoption of URS/RIRS as the new standard of care for nephrolithiasis among young adults.

A machine learning model for predicting surgical intervention in renal colic due to ureteral stone(s) < 5 mm.

A 75-89% expulsion rate is reported for ureteric stones ≤ 5 mm. We explored which parameters predict justified surgical intervention in cases of pain caused by < 5 mm ureteral stones. We retrospectively reviewed all patients with renal colic caused by ureteral stone < 5 mm admitted to our urology department between 2016 and 2021. Data on age, sex, body mass index, the presence of associated hydronephrosis/stranding on images, ureteral side, stone location, medical history, serum blood count, creatinine, C-reactive protein, and vital signs were obtained upon admission. XGboost (XG), a machine learning model has been implemented to predict the need for intervention. A total of 471 patients (median age 49, 83% males) were reviewed. 74% of the stones were located in the distal ureter. 160 (34%) patients who sustained persistent pain underwent surgical intervention. The operated patients had proximal stone location (56% vs. 10%, p < 0.001) larger stones (4 mm vs. 3 mm, p < 0.001), longer length of stay (3.5 vs. 3 days, p < 0.001) and more emergency-room (ER) visits prior to index admission (2 vs. 1, p = 0.007) compared to those who had no surgical intervention. The model accuracy was 0.8. Larger stone size and proximal location were the most important features in predicting the need for intervention. Altogether with pulse and ER visits, they contributed 73% of the final prediction for each patient. Although a high expulsion rate is expected for ureteral stones < 5 mm, some may be painful and drawn out in spontaneous passage. Decision-making for surgical intervention can be facilitated by the use of the present prediction model.

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.

[ROBOT ASSISTED PYELOPLASTY IN ADULTS WITH URETERO-PELVIC JUNCTION OBSTRUCTION (UPJO)].

BACKGROUND: Robotic-pyeloplasty (RP) for uretero-pelvic-junction-obstruction (UPJO) has been performed in our institution since 2013. OBJECTIVES: To summarize the outcomes of RP in adults over 18 years of age. METHODS: Adult RP cases have been prospectively documented. Analysis included demographic data such as age, sex, American Association of Anesthesiology-ASA Score, surgical-side, pre-operative imaging. Operative time (OT), estimated blood loss (EBL), length of stay (LOS) and short-term complications were also recorded. In all cases a JJ-stent has been left in place and subsequently taken out. Complications were classified in accordance with the Clavien-Dindo classification criteria. Patients were seen periodically with repeat imaging. The renal scan was performed at least once during the post-operative follow-up. Results are given as median (inter-quartile range) or numeric values (%). RESULTS: A total of 32 patients aged 33.5 years (21-45.2) had RP between the years 2013-2020, among which 53% were females and 59% right sided. An ASA score of 1-2 has been observed in 87.5% of all cases. Skin-to-skin OT was 163 min (136-185), and EBL was 5 ml (0-30). Short-term post-operative complications were hematuria (3.1%), urinary leak/urinoma (12.5%), body temperature>38.30C (12.5%). In 2 cases (6.2%) the JJ-stent had been re-positioned in the operating-theater (Clavien-Dindo 3b). LOS was 3 days (2-4) and JJ-stent had been taken out 39 days (31.7-45.2) post-operatively. Median length of follow-up was 19.5 months (9.5-26.7). In 92.3% of cases an improvement in hydronephrosis has been observed in post-operative imaging. The renal scan did not demonstrate renal function deterioration. CONCLUSIONS: Adult robotic pyeloplasty for UPJO is safe and effective. Low complication rates and over 90% success rates have been observed. These findings are in line with those found in previous studies.

[UPPER TRACT UROTHELIAL CARCINOMA].

INTRODUCTION: Upper tract urothelial carcinoma is a relatively rare malignancy, but with an increasing prevalence. The main risk factor for the disease is smoking. The most common presentation is hematuria or flank pain. Workup is made by imaging of the upper tract - CTU/MRU (Computed Tomography-Urography/Magnetic resonance (MR) urography) and diagnostic uretero-nephroscopy with biopsy. In the past several years there is major advancement in our understanding of the disease and how to treat it, mainly in nephron-sparing treatments. A risk-stratification is usually conducted according to parameters such as tumor size, distribution, and pathologic diagnosis. The low-risk group is usually offered nephron-sparing treatments such as segmental ureterectomy, endoscopic treatments, and lately - local chemotherapy. The high-risk group is usually offered radical resection of the kidney and ureter, with the possible addition of new-adjuvant and adjuvant treatments. In this article we will review the epidemiology, risk factors, diagnosis, and treatment of this malignancy, with a distinction between the risk groups.

A single day fasting may increase emergency room visits due to renal colic.

We aimed to explore whether a single-day of fasting (SDF) increase emergency room (ER) visits due to renal colic (RC). We elected to concentrate on Yom-Kippur (i.e.: SDF), the holiest day in Judaism. Food and liquid consumption is prohibited during this day for 25 h, and an estimated 50-70% fasting rate is observed. SDF always takes place between mid-September and mid-October during which the temperature in the Middle-East ranges between 19 and 30 °C. ER visits for RC between 01/2012 and 11/2019 were reviewed, and the Gregorian days on which SDF occurred were retrieved. The number of ER visits for RC was compared between SDF and the surrounding days/months as well as to another single-day "standard" holiday (SDSH) that precedes SDF in 10 days and is not associated with fasting. Of 11,717 ER visits for RC, 8775 (74.9%) were males. Male:Female ratio was 3:1. The mean daily number of ER visits for RC during the 3 days following SDF was 6.66 ± 2.49, significantly higher compared with the mean annual daily visits (4.1 ± 2.27, p < 0.001), the mean daily visits during the week prior to SDF (5.27 ± 2.656, p = 0.032), and the mean daily visits during September (5.06 ± 2.659, p = 0.005), and October (4.78 ± 2.23, p < 0.001). The mean number of ER daily visits for RC during the 3 days following SDSH, 5.79 ± 2.84, did not differ compared with the mean daily visits during September and October (p = 0.207; p = 0.13, respectively). It was lower compared to SDF, however statistically insignificant (p = 0.285). A single-day fasting may increase ER visits for RC. The mechanism underlying this phenomenon is unknown.

Pharmacokinetics of UGN-101, a mitomycin-containing reverse thermal gel instilled via retrograde catheter for the treatment of low-grade upper tract urothelial carcinoma.

PURPOSE: To evaluate the pharmacokinetic properties of UGN-101, a mitomycin-containing reverse thermal gel used as primary chemoablative treatment for low-grade upper tract urothelial carcinoma (UTUC), in a subset of patients participating in a phase 3 clinical trial. METHODS: Pharmacokinetic parameters (Cmax, Tmax, AUC(0-6), λz, t½, and AUCinf) were evaluated in six participants (male or female, ≥ 18 years) with biopsy-proven, low-grade UTUC who received the first of 6 once-weekly instillations of UGN-101 to the renal pelvis and calyces via retrograde ureteral catheter. Plasma samples were collected prior to instillation and 30 min, 1, 2, 3, 4, 5, and 6 h post-instillation. Safety was assessed by laboratory evaluations, physical exam, and adverse event monitoring. RESULTS: The mean age of the six participants was 69 years; most were male (5/6) and Caucasian (5/6). Mean (SD) Cmax was 6.24 (4.11) ng/mL and mean Tmax was 1.79 (1.89) hours after instillation. Mean apparent t½ following instillation was 1.27 (0.63) hours. Mean total systemic exposure to mitomycin up to 6 h post-instillation was 20.30 (19.69) ng h/mL. At 6 h post-instillation, mitomycin plasma concentrations of 5/6 participants were < 2 ng/mL. There were no clinically important adverse events or changes in laboratory values in any participant after a single instillation of UGN-101. CONCLUSION: The reverse thermal gel formulation of UGN-101 is associated with higher concentration and extended dwell time of mitomycin in contact with the urothelium of the upper urinary tract while limiting systemic absorption of mitomycin. REGISTRATION: NCT02793128; registered June 8, 2016.

Tandem ureteral stents drainage lowers renal pelvis pressure in malignant ureteral obstruction: Experimental and computational models.

Malignant ureteral obstruction may lead to impaired renal function and requires drainage by a percutaneous nephrostomy tube or an internal ureteric stent. Usage of stiff tandem ureteral stents may decrease stent failure rates. In this paper we combined computational and in vitro models to examine the flow in a malignant ureteral obstruction (MUO) managed by 4 methods of drainage: single soft stent, single stiff stent, soft tandem ureteral stents, and stiff tandem ureteral stents. Pressure at the renal pelvis was the primary outcome of the computational and in vitro models. Different drainage modalities were compared using ANCOVA. Results of computational and in vitro models agreed completely. Drainage by stiff tandem ureteral stents provides lower renal pelvis pressure levels compared with single and soft stents (p < 0.001), especially for high levels of external pressure. Usage of stiff tandem ureteral stents may decrease stent-failure rates and postpone the need for percutaneous nephrostomy tube insertion.

The Impact of Dietary Modifications and Medical Management on 24-Hour Urinary Metabolic Profiles and the Status of Renal Stone Disease in Recurrent Stone Formers.

BACKGROUND: Dietary modifications and patient-tailored medical management are significant in controlling renal stone disease. Nevertheless, the literature regarding effectiveness is sparse. OBJECTIVES: To explore the impact of dietary modifications and medical management on 24-hour urinary metabolic profiles (UMP) and renal stone status in recurrent kidney stone formers. METHODS: We reviewed our prospective registry database of patients treated for nephrolithiasis. Data included age, sex, 24-hour UMP, and stone burden before treatment. Under individual treatment, patients were followed at 6-8 month intervals with repeat 24-hour UMP and radiographic images. Nephrolithiasis-related events (e.g., surgery, renal colic) were also recorded. We included patients with established long-term follow-up prior to the initiation of designated treatment, comparing individual nephrolithiasis status before and after treatment initiation. RESULTS: Inclusion criteria were met by 44 patients. Median age at treatment start was 60.5 (50.2-70.2) years. Male:Female ratio was 3.9:1. Median follow-up was 10 (6-25) years and 5 (3-6) years before and after initiation of medical and dietary treatment, respectively. Metabolic abnormalities detected included: hypocitraturia (95.5%), low urine volume (56.8%), hypercalciuria (45.5%), hyperoxaluria (40.9%), and hyperuricosuria (13.6%). Repeat 24-hour UMP under appropriate diet and medical treatment revealed a progressive increase in citrate levels compared to baseline and significantly decreased calcium levels (P = 0.001 and 0.03, respectively). A significant decrease was observed in stone burden (P = 0.001) and overall nephrolithiasis-related events. CONCLUSIONS: Dietary modifications and medical management significantly aid in correcting urinary metabolic abnormalities. Consequently, reduced nehprolithiasis-related events and better stone burden control is expected.

Very low-dose computerized tomography for confirmation of urinary stone presence.

PURPOSE: To determine whether a modified non-contrast very low-dose computed tomography (VLD-CT) protocol is applicable for confirmation of known urolithiasis. METHODS AND MATERIALS: Consecutive adult patients with a CT scan showing urinary tract stone(s) between 6/2017-12/2018 were included. They were referred to a modified VLD-CT protocol if stone presence was equivocal or if stone location needed reassessment before an endourological interventional procedure. The scanned area was limited to the level of initial stone location caudally. Data on patients' demographics andbody mass index, were collected. The scanned length and radiation dose were calculated. Images were reviewed by two radiologists who assessed stone size and location. Follow-up reference standard included stone passage, surgical removal, and other imaging and clinical information. RESULTS: Sixty-three patients [63 stones, mean BMI 28.7 (range 19-41.9)] were included. VLD-CTs revealed 31 stones in 31 patients, with a mean stone length of 5.5 mm. Fifteen stones remained at the same location, and 16 had migrated, of which two appeared in the bladder. Thirty-two stones were not observed on VLD-CT. The mean span scanned on the VLD-CT was 274 mm (± 80). The average radiation exposure was 1.47 mGy (range 1.09-3.3), and the absorbed dose was 0.77 mSv (range 0.39-1.43), compared to 10.24 mGy (range 1.75-28.9) and 7.87 mSv (range 1.44-18.5) in the previous scan. The mean radiation dose reduction between scans was 89%. On follow-up, all VLD-CT findings were confirmed. CONCLUSION: A modified imaging protocol is applicable for confirmation of stone presence and location by utilizing very low-dose radiation exposure.

Endoscopic Treatment for Large Multifocal Upper Tract Urothelial Carcinoma.

PURPOSE: We reviewed the oncologic and surgical outcomes of endoscopic treatments for low grade upper tract urothelial carcinoma, and assessed the prognostic significance of tumor size, location and multifocality. MATERIALS AND METHODS: We retrospectively reviewed all patients who underwent endoscopic treatment for low grade upper tract urothelial carcinoma at our institution between 2014 and 2019. Tumors were treated with a dual laser generator, which alternately produces holmium and neodymium lasers. A stringent ureteroscopic followup protocol was conducted. We looked for an association between outcome and tumor size, location or multifocality, and for predictive factors for time to local recurrence and progression. RESULTS: The cohort included 59 patients (62 renal units), 27% of tumors were multifocal and 40% were >2 cm. The median followup time was 22 months (IQR 11-41), and the median number of ureteroscopies was 5.5 (4-9). Local recurrence was observed in 46 renal units (74.1%) at a median of 6.5 months after initial surgery. Four patients (6.4%) developed disease progression and were referred for radical surgery: 2 had pathological progression and 2 had a rapid and high volume local recurrence, and 1 later developed metastatic disease. The progression-free rate was 93.2%. Tumor location in kidney (p=0.03, HR 1.95) and multifocality (p=0.005, HR 3.25) significantly predicted time to local recurrence. No factor predicted time to progression. CONCLUSIONS: Ureteroscopic treatment of large, multifocal, low grade upper tract urothelial carcinoma is feasible, does not involve significant complications and has good short-term oncologic outcomes, with a 93.2% progression-free survival rate. Tumors located in the kidney and multifocality yielded shorter time to local recurrence but not progression.

Endoscopic management of upper tract urothelial carcinoma-tips and tricks.

Ureteroscopic methods have been rapidly evolving in the last several decades. With advances in flexible devices, optics and laser technologies, the endourologic surgeon has now the tools to treat high-volume tumors, in difficult locations, with good oncologic outcome. This makes radical nephroureterectomy unnecessary in some cases. Endoscopy in the setting of UTUC will surely continue to evolve and become applicable to a wider selection of patients. In this review we describe the surgical technique and provide tips and tricks which we use in our practice of endoscopic retrograde treatment of upper-tract urothelial carcinoma.

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.

[THE EFFICACY OF ENDOSCOPIC DUAL LASER TREATMENT FOR LOW GRADE UPPER TRACT UROTHELIAL CARCINOMA].

INTRODUCTION: Until recently, radical nephroureterectomy was considered the gold standard treatment for upper tract urothelial carcinoma (UTUC). Post-operative complications, long-term adverse effects of nephrectomy as well as the risk of contralateral recurrence have led to the development of nephron-sparing techniques. OBJECTIVES: To evaluate the safety, complication rate, and oncologic outcomes of ureteroscopic nephron-sparing treatment for low-grade UTUC utilizing a hybrid laser system that incorporates two types of lasers: Nd:YAG and Ho:YAG. METHODS: We reviewed the files of patients who underwent ureteroscopic treatment for UTUC with the hybrid laser system between the years 2014-2018. Only cases of low-grade UTUC and follow-up time of at least 6 months were included in the present study. The following were analyzed: demographic data, tumor histologic characteristics, peri-operative complications, histologic upgrade, oncologic outcomes (i.e: local recurrence, local spread, metastatic progression). RESULTS: A total of 38 patients, who underwent 74 ureteroscopies, met inclusion criteria. Mean tumor size was 16.2 mm. No intra-operative complications were recorded. Two post-operative complications were recorded in one patient - hematuria and retroperitoneal bleeding - both had been treated conservatively. Mean follow-up time was 21.8 months. Local recurrence rate was 73%. Histologic upgrade has been observed in two patients. Four patients (10.5%) were referred to radical nephroureterectomy. There were no cases of local spread, distant metastases or death during the follow-up period. DISCUSSION: Endoscopic dual-laser treatment for low-grade UTUC is safe, surgically feasible and associated with good short-term oncologic outcome. Patient selection and strict follow-up are mandatory.