High-Risk Patients Undergoing Holmium Laser Enucleation of the Prostate Have Fewer Infections with a Longer Course of Preoperative Antibiotics.

Introduction: There are minimal data to guide antibiotic management of patients undergoing holmium laser enucleation of the prostate (HoLEP) for benign prostatic hyperplasia. Specifically, management of high-risk patients who are catheter dependent or have positive preoperative urine cultures varies widely. We aimed to evaluate the effect of preoperative antibiotic duration on infectious complications in high-risk patients undergoing HoLEP. Methods: A multi-institutional retrospective review of patients undergoing HoLEP between 2018 and 2023 at five institutions was performed. Patients were defined as high risk if they were catheter-dependent (indwelling urethral catheter, self-catheterization, or suprapubic tube) or had a positive preoperative urine culture. These patients were categorized into long course (>3 days) or short course (≤3 days) of preoperative antibiotics. The primary outcome was 30-day infectious complications defined as a positive urine culture with symptoms. A t-test or Wilcoxon rank-sum test was used for continuous variables and Fisher's exact test was used for categorical variables. Logistic regression analysis was conducted to identify associations with infectious complications. Results: Our cohort included 407 patients, of which 146 (36%) and 261 (64%) were categorized as short course and long course of preoperative antibiotics, respectively. Median preoperative antibiotic duration was 1 day (interquartile range [IQR]: 0, 3 days) and 7 days (IQR: 5, 7 days) in the short and long cohorts, respectively. Thirty-day postoperative infectious complications occurred in 11 (7.6%) patients who received a short course of antibiotics and 5 (1.9%) patients who received a long course of antibiotics (odds ratio 0.24, 95% confidence interval 0.07-0.67; p = 0.009). Variables such as age, positive urine culture, and postoperative antibiotic duration were not significantly associated with postoperative infection after propensity score weighting. Conclusion: In high-risk patients undergoing HoLEP, infectious complications were significantly lower with a long course vs short course of antibiotics. Further prospective trials are needed to identify optimal preoperative antibiotic regimens.

Natural language processing pipeline to extract prostate cancer-related information from clinical notes.

OBJECTIVES: To develop an automated pipeline for extracting prostate cancer-related information from clinical notes. MATERIALS AND METHODS: This retrospective study included 23,225 patients who underwent prostate MRI between 2017 and 2022. Cancer risk factors (family history of cancer and digital rectal exam findings), pre-MRI prostate pathology, and treatment history of prostate cancer were extracted from free-text clinical notes in English as binary or multi-class classification tasks. Any sentence containing pre-defined keywords was extracted from clinical notes within one year before the MRI. After manually creating sentence-level datasets with ground truth, Bidirectional Encoder Representations from Transformers (BERT)-based sentence-level models were fine-tuned using the extracted sentence as input and the category as output. The patient-level output was determined by compilation of multiple sentence-level outputs using tree-based models. Sentence-level classification performance was evaluated using the area under the receiver operating characteristic curve (AUC) on 15% of the sentence-level dataset (sentence-level test set). The patient-level classification performance was evaluated on the patient-level test set created by radiologists by reviewing the clinical notes of 603 patients. Accuracy and sensitivity were compared between the pipeline and radiologists. RESULTS: Sentence-level AUCs were ≥ 0.94. The pipeline showed higher patient-level sensitivity for extracting cancer risk factors (e.g., family history of prostate cancer, 96.5% vs. 77.9%, p < 0.001), but lower accuracy in classifying pre-MRI prostate pathology (92.5% vs. 95.9%, p = 0.002) and treatment history of prostate cancer (95.5% vs. 97.7%, p = 0.03) than radiologists, respectively. CONCLUSION: The proposed pipeline showed promising performance, especially for extracting cancer risk factors from patient's clinical notes. CLINICAL RELEVANCE STATEMENT: The natural language processing pipeline showed a higher sensitivity for extracting prostate cancer risk factors than radiologists and may help efficiently gather relevant text information when interpreting prostate MRI. KEY POINTS: When interpreting prostate MRI, it is necessary to extract prostate cancer-related information from clinical notes. This pipeline extracted the presence of prostate cancer risk factors with higher sensitivity than radiologists. Natural language processing may help radiologists efficiently gather relevant prostate cancer-related text information.

Access to Care and Health Care Utilization Among Patients With Nephrolithiasis.

OBJECTIVE: To characterize the impact of nephrolithiasis diagnosis and treatment on health care utilization and identify predictors of barriers to care in the patient population. METHODS: We conducted a retrospective cohort study using the All of Us Database, a National Institutes of Health database targeting recruitment of underrepresented populations. Patients with a diagnosis of kidney stones were included and matched to a control group. Primary outcomes were patients' self-reported health care access and utilization. Univariable and multivariable regression analyses were performed. RESULTS: 9173 patients with a diagnosis of nephrolithiasis were included and matched to 9173 controls without a diagnosis of nephrolithiasis. Patients with kidney stones were less likely to have had >1 year since last provider visit (1.7% vs 3.8%, P <.001), but did not report increased delays obtaining care (31%), inability to afford care (11.4%), or higher likelihood of skipping medications (12.9%). Among patients with stones, 1208 (13.2%) had been treated surgically. On multivariable analysis, younger age, female sex, lower income, lower education, non-insured status, and lower physical and mental health were all associated with delays obtaining care, difficulty affording care, skipping medications, and/or prolonged time since seeing a provider. CONCLUSION: A diagnosis of nephrolithiasis and subsequent surgical intervention were not associated with an increase in patient-reported barriers to care. However, among patients with nephrolithiasis, younger, comorbid, female patients from lower socioeconomic status are at significant risk of being unable to access and utilize treatment.

Are adverse events during surgery for benign prostatic hyperplasia device related? A review of the MAUDE database.

PURPOSE: The Manufacturer and User Facility Device Experience database contains anonymous, voluntary medical device reports. A review of device-related adverse events associated with Benign Prostatic Hyperplasia surgeries was completed. The objective was to evaluate the occurrence and contributing factors to clinically significant complications in a cohort of patients electing to undergo surgical intervention for Benign Prostatic Hyperplasia. METHODS: The Manufacturer and User Facility Device Experience database was queried for "Aquablation, Greenlight Laser, Holmium Laser, Morcellator, Water Vapor Thermal Therapy, Loop Resection, and Prostatic Urethral Lift" from 2018 through 2021. A complication classification system (Level I-IV) based on the Clavien-Dindo system was used to categorize events. These events were then correlated with procedural technology malfunctions and classified as "device related" and "non-device related." Chi squared analysis was performed to identify associations between procedural technology and complication classification distribution. RESULTS: A total of 873 adverse events were identified. The adverse events were classified into level I (minimal harm) versus levels II-IV (clinically significant). Aquablation (p < 0.017) and Water Vapor Thermal Therapy (p < 0.012) were associated with a higher proportion of reports with Level II-IV complications compared with other procedure types. Level II-IV complications were not associated with a reported device related malfunction. CONCLUSIONS: Aquablation and water vapor thermal therapy demonstrated noteworthy clinically significant complications which were not driven by device-related malfunctions.

The Impact of Standard vs Early Apical Release Holmium Laser Enucleation of the Prostate Technique on Postoperative Incontinence and Quality of Life.

OBJECTIVE: To investigate the difference in postoperative incontinence and quality of life comparing standard vs early apical release (EAR) Holmium Laser Enucleation of the Prostate (HoLEP). METHODS: A retrospective review was performed to identify patients who underwent HoLEP from December 2021 to December 2022 at a single tertiary referral center with two participating consultant urologists. Patients were assessed with questionnaires and evaluated clinically. We performed propensity score matching with a logistic regression and a 1:1 matching method. A propensity score-adjusted logistic regression (PSRM) was performed to compare the pads per day between surgical techniques controlling for age, prostate size, preoperative survey data, uroflow, and postvoid residual. RESULTS: One hundred fourteen patients underwent HoLEP, of which 60 patients were treated with EAR and 54 patients with standard technique. EAR technique demonstrated shorter operative times (P = .046). The EAR cohort demonstrated improved AUASS (P = .034, P = .001), QOL (P = .001, P <.001), and continence rates (P <.001, P <.001) at 6 and 12weeks postoperatively. PSRM showed that the standard HoLEP increased the risk of requiring ≥2 pads per day 4.2x (P = .031, HR 95%, CI=1.16, 15.35) and 8.3x (P <.001, HR 95% CI 3.17, 21.6) at 6 and 12weeks postoperatively. CONCLUSION: EAR technique promoted earlier return of continence and improved quality of life within 6weeks of surgery.

First analysis of the safety and efficacy of UGN-101 in the treatment of ureteral tumors.

OBJECTIVE: UGN-101 has been approved for the chemoablation of low-grade upper tract urothelial cancer (UTUC) involving the renal pelvis and calyces. Herein is the first reported cohort of patients with ureteral tumors treated with UGN-101. PATIENTS AND METHODS: We performed a retrospective review of patients treated with UGN-101 for UTUC at 15 high-volume academic and community centers focusing on outcomes of patients treated for ureteral disease. Patients received UGN-101 with either adjuvant or chemo-ablative intent. Response rates are reported for patients receiving chemo-ablative intent. Adverse outcomes were characterized with a focus on the rate of ureteral stenosis. RESULTS: In a cohort of 132 patients and 136 renal units, 47 cases had tumor involvement of the ureter, with 12 cases of ureteral tumor only (8.8%) and 35 cases of ureteral plus renal pelvic tumors (25.7%). Of the 23 patients with ureteral involvement who received UGN-101 induction with chemo-ablative intent, the complete response was 47.8%, which did not differ significantly from outcomes in patients without ureteral involvement. Fourteen patients (37.8%) with ureteral tumors had significant ureteral stenosis at first post-treatment evaluation, however, when excluding those with pre-existing hydronephrosis or ureteral stenosis, only 5.4% of patients developed new clinically significant stenosis. CONCLUSIONS: UGN-101 appears to be safe and may have similar efficacy in treating low-grade urothelial carcinoma of the ureter as compared to renal pelvic tumors.

Is Race Associated with the Surgical Treatment for Benign Prostatic Hyperplasia? An Analysis of 30,000 Medicare Lives.

BACKGROUNDS: With an increased prevalence and burden of benign prostatic hyperplasia (BPH), effective and equitable treatment is a priority. Limited data exist evaluating treatment disparities for patients with BPH by race. This study examined the association between race and BPH surgical treatment rates among Medicare beneficiaries. METHODS: Medicare claims data were used to identify men newly diagnosed with BPH from January 1, 2010 through December 31, 2018. Patients were followed until their first BPH surgery, a diagnosis of prostate/bladder cancer, termination of Medicare enrollment, death, or end of study. Cox proportional hazards regression compared the likelihood of BPH surgery between men of different races (White vs. Black, Indigenous, and People of Color (BIPOC)), controlling for patients' geographical region, Charlson comorbidity score, and baseline comorbidities. RESULTS: The study included 31,699 patients (13.7% BIPOC). BIPOC men had significantly lower BPH surgery rates (9.5% BIPOC vs. 13.4% White; p=0.02). BIPOC race was associated with a 19% lower likelihood of receiving BPH surgery than White race (HR, 0.81; 95% CI 0.70, 0.94). Transurethral resection of the prostate was the most common surgery for both groups (49.4% Whites vs. 56.8% BIPOC; p=0.052). A higher proportion of BIPOC men underwent procedures in inpatient settings compared to White men (18.2% vs. 9.8%; p<0.001). CONCLUSIONS: Among a cohort of Medicare beneficiaries with BPH, there were notable treatment disparities by race. BIPOC men had lower rates of surgery than White men and were more likely to undergo procedures in the inpatient setting. Improving patient access to outpatient BPH surgical procedures may help address treatment disparities.

Evaluation of Private Payer and Patient Out-of-Pocket Costs Associated With the Surgical Management of Benign Prostatic Hyperplasia.

OBJECTIVE: To evaluate and compare the financial burden of various surgical interventions for the management of benign prostatic hyperplasia (BPH). METHODS: We identified commercially insured men with a diagnosis of BPH who underwent a procedure of interest (simple prostatectomy (SP), transurethral resection of the prostate (TURP), holmium laser enucleation of the prostate (HoLEP), photovaporization of the prostate (PVP), prostatic urethral lift (PUL), or water vapor thermal therapy (WVTT)) between 2015 and 2021 with the OptumLabs Data Warehouse. Primary outcome was total health care costs (THC) which included both patient out-of-pocket (OOP) and health plan paid costs for the index procedure and combined follow-up years 1-5. A generalized linear model was used to estimate adjusted costs controlling for demographic and clinical characteristics. Patients undergoing WVTT were excluded from extended follow-up analyses due to limited data. RESULTS: Among 25,407 patients with BPH, 10,117 (40%) underwent TURP, 6353 (25%) underwent PUL, 5411 (21%) underwent PVP, 1319 (5%) underwent SP, 1243 (5%) underwent WVTT, and 964 (4%) underwent HoLEP. Index procedure costs varied significantly with WVTT being the least costly [THC: $2637 (95% confidence interval (CI): $2513-$2761)], and SP being the costliest [THC: $14,423 (95% CI: $12,772-$16,075)]. For aggregate index and 5-year follow-up costs, HoLEP ($31,926 [95% CI: $29,704-$34,148]) was the least costly and PUL ($36,596 [95% CI: $35,369-37,823]) was the costliest. CONCLUSION: BPH surgical treatment is associated with significant system-level health care costs. The level of impact varies between procedures. Minimally invasive options, such as WVTT, may offer initial cost reductions; however, HoLEP and SP are associated with lower follow-up costs.

From Consensus to Validation: A Multicenter Study for Design and Development of a Holmium Laser Enucleation of the Prostate Hydrogel Simulation Platform.

Background: Holmium laser enucleation of the prostate (HoLEP) has emerged as a new gold standard for treatment of benign prostatic hyperplasia; however, its steep learning curve hinders generalization of this technique. Therefore, there is a need for a benchtop HoLEP simulator to reduce this learning curve and provide training. We have developed a nonbiohazardous HoLEP simulator using modern education theory and validated it in a multicenter study. Materials and Methods: Six experts established key components for a HoLEP simulator through a Delphi consensus over three rounds including 250 questions. After consensus, a digital design was created and approved by experts, then used to fabricate a physical prototype using three-dimensional printing and hydrogel molding. After a process of iterative prototype testing, experts completed a survey assessing the simulator with a 5-point Likert scale for final approval. The approved model was validated with 56 expert and novice participants at seven institutions using subjective and objective performance metrics. Results: Consensus was reached on 85 of 250 questions, and experts found the physical model to adequately replicate 82.5% of required features. Objective metrics were statistically significant (p < 0.0001) when comparing experts and novices for enucleation time (37.4 ± 8.2 vs 16.7 ± 6.8 minutes), adenoma weight (79.6 ± 20.4 vs 36.2 ± 9.9 g), and complications (6 vs 22), respectively. Conclusion: We have effectively completed a multicenter study to develop and validate a nonbiohazardous benchtop simulator for HoLEP through modern education theory. A training curriculum including this simulator is currently under development.

Cancer Detection Rate and Abnormal Interpretation Rate of Prostate MRI Performed for Clinical Suspicion of Prostate Cancer.

PURPOSE: To report cancer detection rate (CDR) and abnormal interpretation rate (AIR) in prostate MRI performed for clinical suspicion of prostate cancer (PCa). MATERIALS AND METHODS: This retrospective single-institution, three-center study included patients who underwent MRI for clinical suspicion of PCa between 2017 and 2021. Patients with known PCa were excluded. Patient-level Prostate Imaging-Reporting and Data System (PI-RADS) score was extracted from the radiology report. AIR was defined as number of abnormal MRI (PI-RADS score 3-5) / total number of MRIs. CDR was defined as number of clinically significant PCa (csPCa: Gleason score ≥7) detected at abnormal MRI / total number of MRI. AIR, CDR, and CDR adjusted for pathology confirmation rate were calculated for each of three centers and pre-MRI biopsy status (biopsy-naive and previous negative biopsy). RESULTS: A total of 9,686 examinations (8,643 unique patients) were included. AIR, CDR, and CDR adjusted for pathology confirmation rate were 45.4%, 23.8%, and 27.6% for center I; 47.2%, 20.0%, and 22.8% for center II; and 42.3%, 27.2%, and 30.1% for center III, respectively. Pathology confirmation rate ranged from 81.6% to 88.0% across three centers. AIR and CDR for biopsy-naive patients were 45.5% to 52.6% and 24.2% to 33.5% across three centers, respectively, and those for previous negative biopsy were 27.2% to 39.8% and 11.7% to 14.2% across three centers, respectively. CONCLUSION: We reported CDR and AIR in prostate MRI for clinical suspicion of PCa. CDR needs to be adjusted for pathology confirmation rate and pre-MRI biopsy status for interfacility comparison.

Cancer Detection Rate and Abnormal Interpretation Rate of Prostate MRI in Patients With Low-Grade Cancer.

PURPOSE: The aim of this study was to evaluate the utility of cancer detection rate (CDR) and abnormal interpretation rate (AIR) in prostate MRI for patients with low-grade prostate cancer (PCa). METHODS: This three-center retrospective study included patients who underwent prostate MRI from 2017 to 2021 with known low-grade PCa (Gleason score 6) without prior treatment. Patient-level highest Prostate Imaging Reporting & Data System (PI-RADS®) score and pathologic diagnosis within 1 year after MRI were used to evaluate the diagnostic performance of prostate MRI in detecting clinically significant PCa (csPCa; Gleason score ≥ 7). The metrics AIR, CDR, and CDR adjusted for pathologic confirmation rate were calculated. Radiologist-level AIR-CDR plots were shown. Simulation AIR-CDR lines were created to assess the effects of different diagnostic performances of prostate MRI and the prevalence of csPCa. RESULTS: A total of 3,207 examinations were interpreted by 33 radiologists. Overall AIR, CDR, and CDR adjusted for pathologic confirmation rate at PI-RADS 3 to 5 (PI-RADS 4 and 5) were 51.7% (36.5%), 22.1% (18.8%), and 30.7% (24.6%), respectively. Radiologist-level AIR and CDR at PI-RADS 3 to 5 (PI-RADS 4 and 5) were in the 36.8% to 75.6% (21.9%-57.5%) range and the 16.3%-28.7% (10.9%-26.5%) range, respectively. In the simulation, changing parameters of diagnostic performance or csPCa prevalence shifted the AIR-CDR line. CONCLUSIONS: The authors propose CDR and AIR as performance metrics in prostate MRI and report reference performance values in patients with known low-grade PCa. There was variability in radiologist-level AIR and CDR. Combined use of AIR and CDR could provide meaningful feedback for radiologists to improve their performance by showing relative performance to other radiologists.

Decreased prostate MRI cancer detection rate due to moderate to severe susceptibility artifacts from hip prosthesis.

OBJECTIVES: To evaluate the impact of susceptibility artifacts from hip prosthesis on cancer detection rate (CDR) in prostate MRI. MATERIALS AND METHODS: This three-center retrospective study included prostate MRI studies for patients without known prostate cancer between 2017 and 2021. Exams with hip prosthesis were searched on MRI reports. The degree of susceptibility artifact on diffusion-weighted images was retrospectively categorized into mild, moderate, and severe (> 66%, 33-66%, and < 33% of the prostate volume are evaluable) by blind reviewers. CDR was defined as the number of exams with Gleason score ≥7 detected by MRI (PI-RADS ≥3) divided by the total number of exams. For each artifact grade, control exams without hip prosthesis were matched (1:6 match), and CDR was compared. The degree of CDR reduction was evaluated with ratio, and influential factors were evaluated by expanding the equation. RESULTS: Hip arthroplasty was present in 548 (4.8%) of the 11,319 MRI exams. CDR of the cases and matched control exams for each artifact grade were as follows: mild (n = 238), 0.27 vs 0.25, CDR ratio = 1.09 [95% CI: 0.87-1.37]; moderate (n = 143), 0.18 vs 0.27, CDR ratio = 0.67 [95% CI: 0.46-0.96]; severe (n = 167), 0.22 vs 0.28, CDR ratio = 0.80 [95% CI: 0.59-1.08]. When moderate and severe artifact grades were combined, CDR ratio was 0.74 [95% CI: 0.58-0.93]. CDR reduction was mostly attributed to the increased frequency of PI-RADS 1-2. CONCLUSION: With moderate to severe susceptibility artifacts from hip prosthesis, CDR was decreased to 74% compared to the matched control. CLINICAL RELEVANCE STATEMENT: Moderate to severe susceptibility artifacts from hip prosthesis may cause a non-negligible CDR reduction in prostate MRI. Expanding indications for systematic prostate biopsy may be considered when PI-RADS 1-2 was assigned. KEY POINTS: • We proposed cancer detection rate as a diagnostic performance metric in prostate MRI. • With moderate to severe susceptibility artifacts secondary to hip arthroplasty, cancer detection rate decreased to 74% compared to the matched control. • Expanding indications for systematic prostate biopsy may be considered when PI-RADS 1-2 is assigned.

Surgical Site Infections in Open and Laparoscopic Operations in Rooms With Open-floor Drainage Systems.

INTRODUCTION: Surgical site infections are common postoperative complications. Some operating rooms have open-floor drainage systems for fluid disposal during endourologic cases, although nonendoscopy cases are not always allowed in these rooms. We hypothesized that operating rooms with open-floor drainage systems would not materially affect risk of surgical site infections for patients undergoing open and laparoscopic procedures. METHODS: Patients who had surgical site infections from 2016 through 2020 were identified from data of the National Surgical Quality Improvement Program. Patients without surgical incisions, with open wounds, and with surgical site infections at surgery were excluded. The primary outcome was surgical site infection occurrence within 30 days of surgery. Multilevel multivariable logistic regression was used to estimate the observed-to-expected surgical site infection ratio for each operating room (2 with and 23 without open-floor drainage systems). RESULTS: We identified 8,419 surgical cases, of which 802 (9.5%) were performed in operating rooms with open-floor drainage systems; 166 patients (2.0%) had surgical site infections. Of the surgical site infections, 7 (4.2%) occurred in operating rooms with open-floor drainage systems. Surgical specialty, American Society of Anesthesiologists physical status, higher case acuity, dyspnea, immunosuppression, longer surgical duration, and wound classification were associated with surgical site infections (P < .05 for all). The observed-to-expected ratios of surgical site infections occurring in the 2 operating rooms with open-floor drainage systems were 0.85 and 1.15. The odds ratio of surgical site infections for urologic cases performed in room with vs without open-floor drainage systems was 1.30 (P = .65). CONCLUSIONS: Urology operating room designs often include open-floor drainage systems for water-based cases. These drainage systems were not associated with an increased risk of surgical site infections.

Route of Administration for UGN-101 and Impact on Oncological and Safety Outcomes.

BACKGROUND: UGN-101 can be used for chemoablation of low-grade upper tract urothelial carcinoma (UTUC). The gel can be administered via a retrograde route through a ureteral catheter or an antegrade route via a nephrostomy tube. OBJECTIVE: To report outcomes of UGN-101 by route of administration. DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective review of 132 patients from 15 institutions who were treated with UGN-101 for low-grade UTUC via retrograde versus antegrade administration. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Survival outcomes are reported per patient. Treatment, complications, and recurrence outcomes are reported per renal unit. Statistical analysis was performed for primary endpoints of oncological response and ureteral stricture occurrence. RESULTS AND LIMITATIONS: A total of 136 renal units were evaluated, comprising 78 retrograde and 58 antegrade instillations. Median follow-up was 7.4 mo. There were 120 cases (91%) of biopsy-proven low-grade UTUC. Tumors were in the renal pelvis alone in 89 cases (65%), in the ureter alone in 12 cases (9%), and in both in 35 cases (26%). Seventy-six patients (56%) had residual disease before UGN-101 treatment. Chemoablation with UGN-101 was used in 50/78 (64%) retrograde cases and 26/58 (45%) antegrade cases. A complete response according to inspection and cytology was achieved in 31 (48%) retrograde and 30 (60%) antegrade renal units (p = 0.1). Clavien grade 3 ureteral stricture occurred in 21 retrograde cases (32%) and only six (12%) antegrade cases (p < 0.01). Limitations include treatment bias, as patients in the antegrade group were more likely to undergo endoscopic mechanical ablation before UGN-101 instillation. CONCLUSIONS: These preliminary results show a significantly lower rate of stricture occurrence with antegrade administration of UGN-101, with no apparent impact on oncological efficacy. PATIENT SUMMARY: We compared results for two different delivery routes for the drug UGN-101 for treatment of cancer in the upper urinary tract. For the antegrade route, a tube is inserted through the skin into the kidney. For the retrograde route, a catheter is inserted past the bladder into the upper urinary tract. Our results show a lower rate of narrowing of the ureter (the tube draining urine from the kidney into the bladder) using the antegrade route, with no difference in cancer control.

Quick Sequential Organ Failure Assessment Score Is a Better Predictor of Septic Shock After Percutaneous Nephrolithotomy: A Secondary Analysis of Two Multicenter Prospective Trials.

Introduction: Recent retrospective literature suggests that the quick sequential organ failure assessment (qSOFA) scoring tool is a potentially superior tool over use of the systemic inflammatory response syndrome (SIRS) criteria to predict septic shock after percutaneous nephrolithotomy (PCNL) surgery. Here we examine use of qSOFA and SIRS to predict septic shock within data series collected prospectively on PCNL patients as part of a greater study of infectious complications. Materials and Methods: We performed a secondary analysis of two prospective multicenter studies including PCNL patients across nine institutions. Clinical signs informing SIRS and qSOFA scores were collected no later than postoperative day 1. The primary outcome was sensitivity and specificity of SIRS and qSOFA (high-risk score of greater-or-equal to two points) in predicting admission to the intensive care unit (ICU) for vasopressor support. Results: A total of 218 cases at 9 institutions were analyzed. One patient required vasopressor support in the ICU. The sensitivity/specificity was 100%/72.4% (McNemar's test p < 0.001) for SIRS and was 100%/90.8% (McNemar's test p < 0.001) for qSOFA. Conclusion: Although positive predictive value for both qSOFA and SIRS in prediction of post-PCNL septic shock is low, prospectively collected data demonstrate use of qSOFA may offer greater specificity than SIRS criteria when predicting post-PCNL septic shock.

The ablative effect of mitomycin reverse thermal gel: Expanding the role for nephron preservation therapy in low grade upper tract urothelial carcinoma.

PURPOSE: Assess the real-world ablative effect of mitomycin reverse thermal gel for low-grade upper tract urothelial carcinoma (UTUC) in patients who undergo biopsy only or partial ablation and evaluate utility of complete ablation prior to UGN-101. MATERIAL AND METHODS: We retrospectively reviewed low-grade UTUC patients treated with UGN-101 from 15 high-volume centers. Patients were categorized based on initial endoscopic ablation (biopsy only, partial ablation, or complete ablation) and by size of remaining tumor (complete ablation, <1cm, 1-3cm, or >3cm) prior to UGN-101. The primary outcome was rendered disease free (RDF) rate at first post-UGN-101 ureteroscopy (URS), defined as complete response or partial response with minimal mechanical ablation to endoscopically clear the upper tract of visible disease. RESULTS: One hundred and sixteen patients were included for analysis after excluding those with high-grade disease. At first post-UGN-101 URS, there were no differences in RDF rates between those who at initial URS (pre-UGN-101) had complete ablation (RDF 77.0%), partial ablation (RDF 55.9%) or biopsy only (RDF 66.7%) (P = 0.14). Similarly, a complimentary analysis focusing on tumor size (completely ablated, <1cm, 1-3cm or >3cm) prior to UGN-101 induction did not demonstrate significant differences in RDF rates (P = 0.17). CONCLUSION: The results of the early real-world experience suggest that UGN-101 may play a role in initial chemo-ablative cytoreduction of larger volume low-grade tumors that may not initially appear to be amenable to renal preservation. Further studies will help to better quantify the chemo-ablative effect and to identify clinical factors for patient selection.

Extensive intratumor regional epigenetic heterogeneity in clear cell renal cell carcinoma targets kidney enhancers and is associated with poor outcome.

BACKGROUND: Clear cell renal cell cancer (ccRCC), the 8th leading cause of cancer-related death in the US, is challenging to treat due to high level intratumoral heterogeneity (ITH) and the paucity of druggable driver mutations. CcRCC is unusual for its high frequency of epigenetic regulator mutations, such as the SETD2 histone H3 lysine 36 trimethylase (H3K36me3), and low frequency of traditional cancer driver mutations. In this work, we examined epigenetic level ITH and defined its relationships with pathologic features, aspects of tumor biology, and SETD2 mutations. RESULTS: A multi-region sampling approach coupled with EPIC DNA methylation arrays was conducted on a cohort of normal kidney and ccRCC. ITH was assessed using DNA methylation (5mC) and CNV-based entropy and Euclidian distances. We found elevated 5mC heterogeneity and entropy in ccRCC relative to normal kidney. Variable CpGs are highly enriched in enhancer regions. Using intra-class correlation coefficient analysis, we identified CpGs that segregate tumor regions according to clinical phenotypes related to tumor aggressiveness. SETD2 wild-type tumors overall possess greater 5mC and copy number ITH than SETD2 mutant tumor regions, suggesting SETD2 loss contributes to a distinct epigenome. Finally, coupling our regional data with TCGA, we identified a 5mC signature that links regions within a primary tumor with metastatic potential. CONCLUSION: Taken together, our results reveal marked levels of epigenetic ITH in ccRCC that are linked to clinically relevant tumor phenotypes and could translate into novel epigenetic biomarkers.

Mitomycin Gel (UGN-101) as a Kidney-sparing Treatment for Upper Tract Urothelial Carcinoma in Patients with Imperative Indications and High-grade Disease.

BACKGROUND: Intracavitary UGN-101 is approved for the treatment of low-grade noninvasive upper tract urothelial carcinoma (UTUC). Post-commercialization studies underscore the benefit of UGN-101 administration for patients with imperative indications for whom radical nephroureterectomy (RNU) is not a viable option. OBJECTIVE: To describe the use, efficacy, and safety of UGN-101 in patients with UTUC with imperative indications for renal preservation, including high-grade disease. DESIGN, SETTING, AND PARTICIPANTS: Patients receiving UGN-101 with imperative indications were retrospectively analyzed using a multicenter centralized registry from 15 high-volume academic and community centers. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We defined imperative indications as patients with a solitary kidney, the presence of chronic kidney disease (CKD) with a glomerular filtration rate <30 ml/min, bilateral UTUC, and patients unfit for or unwilling to undergo surgical extirpation. Tumor characteristics, disease progression/recurrence, and adverse events were recorded on a per-renal-unit basis. RESULTS AND LIMITATIONS: UGN-101 was instilled into 52 renal units (38%) in 48 patients for imperative indications, including 29 patients (56%) with a solitary kidney, 11 kidneys (21%) in the setting of bilateral UTUC, six patients (12%) with CKD, and six patients (12%) who were unfit for or unwilling to undergo RNU. Twelve renal units had biopsy-proven high-grade papillary disease. Tumors were completely ablated before induction therapy in 34% of cases, while 66% had tumor present. Following induction therapy, 17 patients (40%) had no evidence of disease (NED) on ureteroscopy, 88% of whom maintained this status at median follow-up of 10.8 mo. In the cohort with high-grade disease, five patients (45%) had NED at initial post-induction primary disease evaluation. Adverse events included pyelonephritis (8%), ureteral stenosis (8%), anemia (6%), and acute renal failure (4%). Limitations include the retrospective study design, the lack of long-term follow up, and patient selection bias. CONCLUSIONS: Intracavitary therapy with UGN-101 in patients with UTUC and imperative indications shows promise as a kidney-sparing treatment modality. While long-term follow-up is needed, this intracavitary treatment may help in prolonging time to RNU and delaying the morbidity of hemodialysis in this comorbid population. PATIENT SUMMARY: We reviewed results for patients with cancer in the upper urinary tract and an additional condition that would not allow kidney removal who received treatment with a gel called UGN-101. Our results suggest that UGN-101 shows promise as a kidney-sparing treatment. It may delay the time until kidney removal is needed in these patients and avoid the negative effects associated with dialysis.