Lipid biosynthesis perturbation impairs endoplasmic reticulum-associated degradation.

The relationship between lipid homeostasis and protein homeostasis (proteostasis) is complex and remains incompletely understood. We conducted a screen for genes required for efficient degradation of Deg1-Sec62, a model aberrant translocon-associated substrate of the endoplasmic reticulum (ER) ubiquitin ligase Hrd1, in Saccharomyces cerevisiae. This screen revealed that INO4 is required for efficient Deg1-Sec62 degradation. INO4 encodes one subunit of the Ino2/Ino4 heterodimeric transcription factor, which regulates expression of genes required for lipid biosynthesis. Deg1-Sec62 degradation was also impaired by mutation of genes encoding several enzymes mediating phospholipid and sterol biosynthesis. The degradation defect in ino4Δ yeast was rescued by supplementation with metabolites whose synthesis and uptake are mediated by Ino2/Ino4 targets. Stabilization of a panel of substrates of the Hrd1 and Doa10 ER ubiquitin ligases by INO4 deletion indicates ER protein quality control is generally sensitive to perturbed lipid homeostasis. Loss of INO4 sensitized yeast to proteotoxic stress, suggesting a broad requirement for lipid homeostasis in maintaining proteostasis. A better understanding of the dynamic relationship between lipid homeostasis and proteostasis may lead to improved understanding and treatment of several human diseases associated with altered lipid biosynthesis.

NCCN Guidelines® Insights: Bladder Cancer, Version 3.2024.

Bladder cancer, the sixth most common cancer in the United States, is most commonly of the urothelial carcinoma histologic subtype. The clinical spectrum of bladder cancer is divided into 3 categories that differ in prognosis, management, and therapeutic aims: (1) non-muscle-invasive bladder cancer (NMIBC); (2) muscle invasive, nonmetastatic disease; and (3) metastatic bladder cancer. These NCCN Guidelines Insights detail recent updates to the NCCN Guidelines for Bladder Cancer, including changes in the fifth edition of the WHO Classification of Tumours: Urinary and Male Genital Tumours and how the NCCN Guidelines aligned with these updates; new and emerging treatment options for bacillus Calmette-Guérin (BCG)-unresponsive NMIBC; and updates to systemic therapy recommendations for advanced or metastatic disease.

NCCN Guidelines® Insights: Bladder Cancer, Version 2.2022.

The NCCN Guidelines for Bladder Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with bladder cancer and other urinary tract cancers (upper tract tumors, urothelial carcinoma of the prostate, primary carcinoma of the urethra). These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines regarding the treatment of non-muscle-invasive bladder cancer, including how to treat in the event of a bacillus Calmette-Guérin (BCG) shortage; new roles for immune checkpoint inhibitors in non-muscle invasive, muscle-invasive, and metastatic bladder cancer; and the addition of antibody-drug conjugates for metastatic bladder cancer.

Epitaxial Growth of a Thin Layer of Putative Cancer Cells under Limited Resources and in the Presence of an Alkylating Agent.

The dynamics of the Eden cluster in a 32x32 lattice is implemented using a stochastic model. A single-type of cells solid tumor is assumed. Duplication is probabilistic, and occurs when there is room in the immediate surroundings of a cell, otherwise the cell is inhibited by contact. The growth is epitaxial, the shape of the cluster is disk-like; the ratio between the numbers of perimeter cells; and bulk cells decreases as the cluster grows. Percolation is flagged by an inflection in the rate of growth. We assume that the inflection point actually flags a shortage of nutrients, thereafter the rate of growth decreases to zero. Cancer cells in culture, when deprived of nutrients, actually exhibit a similar behavior. Under the logistic hypothesis, the lattice contains nutrients to sustain the growth up to 1024 cells. The model is expanded to include a drug that pollutes the environment. The drug is an alkylating agent that hinders duplication, eventually causing the death of the cell. The logistic equation accounts for drug consumption. The probability of duplication with the drug decreases as the drug is consumed, eventually leading to relapse. Relapses and survival times are investigated as a function of the dose injected.

Overlapping function of Hrd1 and Ste24 in translocon quality control provides robust channel surveillance.

Translocation of proteins across biological membranes is essential for life. Proteins that clog the endoplasmic reticulum (ER) translocon prevent the movement of other proteins into the ER. Eukaryotes have multiple translocon quality control (TQC) mechanisms to detect and destroy proteins that persistently engage the translocon. TQC mechanisms have been defined using a limited panel of substrates that aberrantly occupy the channel. The extent of substrate overlap among TQC pathways is unknown. In this study, we found that two TQC enzymes, the ER-associated degradation ubiquitin ligase Hrd1 and zinc metalloprotease Ste24, promote degradation of characterized translocon-associated substrates of the other enzyme in Saccharomyces cerevisiae Although both enzymes contribute to substrate turnover, our results suggest a prominent role for Hrd1 in TQC. Yeast lacking both Hrd1 and Ste24 exhibit a profound growth defect, consistent with overlapping function. Remarkably, two mutations that mildly perturb post-translational translocation and reduce the extent of aberrant translocon engagement by a model substrate diminish cellular dependence on TQC enzymes. Our data reveal previously unappreciated mechanistic complexity in TQC substrate detection and suggest that a robust translocon surveillance infrastructure maintains functional and efficient translocation machinery.

The Impact of Agent Orange Exposure on Prostate Cancer Outcomes.

PURPOSE: In this study we explored the effect of Agent Orange exposure on prostate cancer survival in VA (Veterans Affairs) patients receiving androgen deprivation therapy for advanced prostate cancer. MATERIALS AND METHODS: We retrospectively examined the association between Agent Orange exposure in men with prostate cancer in national VA databases who were being treated with androgen deprivation therapy. Patients were diagnosed with prostate cancer from 2000 to 2008 with followup through May 2016. Clinical, pathological and demographic variables were compared by Agent Orange exposure. Associations of Agent Orange with overall survival, skeletal related events and cancer specific survival were performed using adjusted Cox proportional hazard models after IPSW (inverse propensity score weighted) adjustment. RESULTS: Overall 87,344 patients were identified. The 3,475 Agent Orange exposed patients were younger (p <0.001), had lower prostate specific antigen (p = 0.002) and were more likely to receive local therapy and chemotherapy (p <0.001) than the 83,869 nonexposed patients. The Charlson comorbidity index was similar in the groups (p = 0.40). After IPSW adjustment Agent Orange exposure was associated with improved overall survival (HR 0.84, 95% CI 0.73-0.97, p = 0.02). However, no difference was observed in the risk of skeletal related events (HR 1.04, 95% CI 0.80-1.35, p = 0.77) or cancer specific survival (HR 0.79, 95% CI 0.60-1.03, p = 0.08). CONCLUSIONS: Agent Orange exposure was associated with a decreased risk of death in men receiving androgen deprivation therapy for advanced prostate cancer. It does not appear to be associated with worse oncologic outcomes.

Impact of bilateral biopsy-detected prostate cancer on an active surveillance population.

BACKGROUND: To assess factors that can predict active surveillance (AS) failure on serial transrectal ultrasound guided biopsies in patients with low-risk prostate cancer. METHODS: We evaluated the records of 144 consecutive patients enrolled in AS between 2007 and 2014 at a single academic institution. Low risk inclusion criteria included PSA < 10 ng/ml, cT1c or cT2a, Grade Group (GG) 1, < 3 positive cores, and < 50% tumor in a single core with the majority having a PSA density of < 0.15. AS reclassification was defined as progression to GG ≥2, 3 or more cores, or core tumor volume ≥ 50%. Univariate and multivariate Cox proportional hazards regression analysis was used to determine predictors of reclassification and a match-pair analysis performed on a control group of patients choosing surgery. RESULTS: Inclusion criteria were met by 130 men with a median follow-up of 52 months. The reclassification or AS failure rate was 38.5%, with the majority 41/50 (82%) finding GG ≥ 2 cancer. Most patients had unilateral disease on diagnostic biopsy (94.6%), but 40.7% had bilateral cancer detected during follow-up. Men with bilateral detected tumor were more likely to ultimately fail AS than patients with unilateral tumors (HR 4.089; P < 0.0001) and failed earlier with a reclassification-free survival of 32 vs 119 months respectively. In a matched-pair analysis using a population of 211 concurrent patients that chose radical prostatectomy rather than AS, 76% of patients with unilateral cancer on biopsy had bilateral cancer on final pathology. CONCLUSIONS: The finding of bilateral prostate cancer on biopsy is associated with earlier AS reclassification. Finding bilateral disease may not represent disease progression, but rather enhanced detection of more extensive disease highlighting the importance of confirmatory biopsy.

Reflex urine culture testing in an ambulatory urology clinic: Implications for antibiotic stewardship in urology.

OBJECTIVES: To evaluate the performance characteristics of urinalysis and urine microscopy parameters for predicting urine culture results and to implement a reflex urine culture program. METHODS: We reviewed the charts of all patients presenting to our clinic January-March 2013 and June-August 2014, excluding those who were catheter-dependent or with urinary diversions. We assessed the association of urinalysis and urine microscopy parameters on urine culture outcomes defining a positive urinalysis as nitrite-positive and/or the presence of ≥5 white blood cells per high-powered field with bacteria and a positive urine culture as ≥10 000 colony-forming units/mL excluding diphtheroids. We carried out logistic regression to assess for predictors of positive urine culture to inform implementation of a reflex urine culture program. RESULTS: A total of 2764 patients were evaluated. Logistic regression using urinalysis variables identified positive nitrites (odds ratio 18.6, P < 0.001) and large leukocyte esterase (odds ratio 41.8, P < 0.001) as the strongest predictors of positive urine culture. Logistic regression using urine microscopy variables identified >50 white blood cells per high-powered field (odds ratio 13.6, P < 0.001) and moderate/many bacteria (odds ratio 16.8, P < 0.001) as the strongest predictors of positive urine culture. We used our positive urinalysis definition to implement the reflex urine culture program and noted a 60% reduction in urine culture rates over the first 3 months of implementation. CONCLUSIONS: A urine positive for nitrites and/or ≥50 white blood cells per high powered field with bacteria seems to have a strong association with a positive urine culture and the best negative predictive value. A reflex urine culture program is an effective strategy to decrease the rates of unnecessary urine culture and their associated costs.

Metformin Use is Associated with Improved Survival for Patients with Advanced Prostate Cancer on Androgen Deprivation Therapy.

PURPOSE: Metformin is commonly prescribed for patients with type 2 diabetes mellitus. We hypothesized that metformin plus androgen deprivation therapy may be beneficial in combination. Our objective was to assess this combination in a retrospective cohort of patients with advanced prostate cancer. MATERIALS AND METHODS: Using national Veterans Affairs databases we identified all men diagnosed with prostate cancer between 2000 and 2008 who were treated with androgen deprivation therapy with followup through May 2016. Study exclusions included treatment with androgen deprivation therapy for 6 months or longer, or receipt of androgen deprivation therapy concurrently with localized radiation. Three patient cohorts were developed, including no diabetes mellitus, diabetes mellitus with no metformin and diabetes mellitus with metformin. Cox proportional HRs were calculated for overall survival, skeletal related events and cancer specific survival. RESULTS: After exclusions the cohort consisted of 87,344 patients, including 61% with no diabetes mellitus, 22% with diabetes mellitus and no metformin, and 17% with diabetes mellitus on metformin. Cox proportional hazard analysis of overall survival showed improved survival in men with diabetes mellitus on metformin (HR 0.82, 95% CI 0.78-0.86) compared to those with diabetes mellitus who were not on metformin (HR 1.03, 95% CI 0.99-1.08). The reference group was men with no diabetes mellitus. Cox proportional hazard analysis of predictors of skeletal related events revealed a HR of 0.82 (95% CI 0.72-0.93) in men with diabetes mellitus on metformin. Cox proportional hazard analysis of cancer specific survival showed improved survival in men with diabetes mellitus on metformin (HR 0.70, 95% CI 0.64-0.77) vs those with diabetes mellitus without metformin (HR 0.93, 95% CI 0.85- 1.00). The reference group was men with no diabetes mellitus. CONCLUSIONS: Metformin use in veterans with prostate cancer who receive androgen deprivation therapy is associated with improved oncologic outcomes. This association should be evaluated in a prospective clinical trial.

Reduced estimated glomerular filtration rate (eGFR <60 mL/min/1.73 m2 ) at first transurethral resection of bladder tumour is a significant predictor of subsequent recurrence and progression.

OBJECTIVE: To evaluate if moderate chronic kidney disease [CKD; estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 ] is associated with high rates of non-muscle-invasive bladder cancer (NMIBC) recurrence or progression. PATIENTS AND METHODS: A multi-institutional database identified patients with serum creatinine values prior to first transurethral resection of bladder tumour (TURBT). The CKD-epidemiology collaboration formula calculated patient eGFR. Cox proportional hazards models evaluated associations with recurrence-free (RFS) and progression-free survival (PFS). RESULTS: In all, 727 patients were identified with a median (interquartile range [IQR]) patient age of 69.8 (60.1-77.6) years. Data for eGFR were available for 632 patients. During a median (IQR) follow-up of 3.7 (1.5-6.5) years, 400 (55%) patients had recurrence and 145 (19.9%) patients had progression of tumour stage or grade. Moderate or severe CKD was identified in 183 patients according to eGFR. Multivariable analysis identified an eGFR of <60 mL/min/1.73 m2 (hazard ratio [HR] 1.5, 95% confidence interval [CI]: 1.2-1.9; P = 0.002) as a predictor of tumour recurrence. The 5-year RFS rate was 46% for patients with an eGFR of ≥60 mL/min/1.73 m2 and 27% for patients with an eGFR of <60 mL/min/1.73 m2 (P < 0.001). Multivariable analysis showed that an eGFR of <60 mL/min/1.73 m2 (HR 3.7, 95% CI: 1.75-7.94; P = 0.001) was associated with progression to muscle-invasive disease. The 5-year PFS rate was 83% for patients with an eGFR of ≥60 mL/min/1.73 m2 and 71% for patients with an eGFR of <60 mL/min/1.73 m2 (P = 0.01). CONCLUSION: Moderate CKD at first TURBT is associated with reduced RFS and PFS. Patients with reduced renal function should be considered for increased surveillance.

Prostate Biopsy in Active Surveillance Protocols: Immediate Re-biopsy and Timing of Subsequent Biopsies.

PURPOSE OF REVIEW: This manuscript reviews contemporary literature regarding prostate cancer active surveillance (AS) protocols as well as other tools that may guide the management of biopsy frequency and assess the possibility of progression in low-risk prostate cancer. RECENT FINDINGS: There is no consensus regarding the timing of surveillance biopsies; however, an immediate repeat biopsy within 12 months of diagnosis for patients considering AS confirms patients who have favorable risk disease yet also identifies patients who were undersampled initially. Studies regarding multiparametric MRI, nomograms, and biomarkers show promise in risk stratifying and counseling patients during AS. Further studies are needed to determine if these supplemental tests can decrease the frequency of surveillance biopsies. An immediate re-biopsy can help to reduce the risk of missing clinically significant disease. Other clinical tools, including mpMRI, exist that can be used as an adjunct to counsel patients and guide a personalized discussion regarding the frequency of surveillance biopsies.

Utility of routine urinalysis and urine culture testing in an ambulatory urology clinic: a quality improvement initiative in a Veterans healthcare facility.

INTRODUCTION: Urinalysis (UA) and urine culture (UCx) are commonly performed tests in the urology clinic. Many of these urine studies are performed prior to the patient visit may not always be indicated, thus contributing to unintended consequences such as antibiotic use and costs without enhancing patient care. Our objective was to perform a quality improvement initiative aimed to assess the utility of routine UA/UCx. MATERIALS AND METHODS: The practice pattern at our site's Veteran Affairs (VA) urology clinic prior to 2014 was to obtain routine UA/UCx on most clinic visits prior to patient evaluation. Starting in 2014, we designed an intervention whereby our nurse practitioner triaged all new patient referrals and selectively ordered UA/UCx. We performed multivariable logistic regression to assess for predictors of obtaining UA or UCx. RESULTS: A total of 1308 patients were seen in January-March 2013 and 1456 in June-August 2014 and were included in this analysis. Fewer patients in 2014 received UA (59.8% versus 70.0%, p < 0.001) and UCx (49.6% versus 64.2%, p < 0.001). There was a decreased odds of obtaining UA in 2014 (OR 0.52, p < 0.001) as well as a decreased odds of obtaining UCx in 2014 (OR0.38, p < 0.001) on multivariable logistic regression. The results of UA/UCx only rarely resulted in change of management in either cohort (3%). Selective ordering resulted in an estimated cost savings of $4915.08/month in UCx costs alone. CONCLUSIONS: Our quality improvement initiatives reduced rates of UA/UCx testing when providers assess patients prior to ordering these tests. The implication of this initiative is significant cost savings for the healthcare system.

Extreme obesity does not predict poor cancer outcomes after surgery for renal cell cancer.

OBJECTIVE: To assess whether extreme obesity (body mass index [BMI] ≥ 40 kg/m(2) ) is associated with peri-operative outcomes, overall survival (OS), cancer-specific survival (CSS), or recurrence-free survival (RFS) after surgical treatment for renal cell carcinoma (RCC). PATIENTS AND METHODS: After institutional review board approval, we used an institutional database to identify patients treated surgically between January 2000 and December 2014 with a pathological diagnosis of RCC. Comprehensive clinical and pathological data were reviewed. Kaplan-Meier analyses were used to estimate OS, RFS and CSS. Univariate and multivariate Cox proportional hazards analysis was used to evaluate associations with OS, CSS and RFS in patients with extreme obesity, among other known predictive variables. RESULTS: In all, 100 patients (11.9%) with a BMI ≥ 40 kg/m(2) and 743 patients (88.1%) with a BMI < 40 kg/m(2) who were treated surgically for RCC were identified. Morbid obesity was not associated with an increased risk of blood transfusion (odds ratio [OR] 1, 95% confidence interval [CI] 0.587-1.70; P = 1.0). The median (interquartile range) length of hospital stay (LOS) was 4 (3-6) days. Morbid obesity was not associated with longer LOS (P = 0.26) or 30-day hospital readmission rates (P = 1.0). Major complications (Clavien ≥ 3a) were recorded in 67 patients (7.95%). BMI ≥ 40 kg/m(2) was not a predictor of major complications (OR 0.58, 95% CI 0.227-1.47; P = 0.251) or 90-day mortality (P = 0.4067). BMI ≥ 40 kg/m(2) was not associated with worse OS (P = 0.7), CSS (P = 0.2) or RFS (P = 0.5). BMI ≥ 35 kg/m(2) was also not associated with worse OS, CSS or RFS (P = 0.3, 0.1, 0.5, respectively). The 5-year OS rate was 68.9% for the entire cohort, including 69 and 70% for patients with BMI < 40 kg/m(2) and BMI ≥ 40 kg/m(2) , respectively (P = 0.69). The 5-year CSS was 79.5% for the entire cohort, including 78.4 and 87.9% (P = 0.16) for patients with BMI < 40 kg/m(2) and BMI ≥ 40 kg/m(2) , respectively. The 5-year RFS rates for BMI < 40 kg/m(2) and BMI ≥ 40 kg/m(2) were 84.1 and 90.6%, respectively (P = 0.48). CONCLUSIONS: Extreme obesity is not associated with worse peri-operative or cancer outcomes after surgery for RCC. Surgery should remain a standard treatment option in well selected morbidly obese patients.

Surveillance following surgery for nonmetastatic renal cell carcinoma.

PURPOSE OF REVEIW: Approximately one in three patients with nonmetastatic renal cell carcinoma (RCC) at the time of surgery will subsequently develop local or metastatic recurrence. The purpose of this review is to examine the current rationale for surveillance, describe sites of RCC metastasis, evaluate the existing guidelines for postsurgical follow-up studies, and analyze the risk stratification systems following RCC surgery. RECENT FINDINGS: Although 75% of recurrences will be identified during the first 5 years following surgery, late recurrences are not uncommon. The risk of recurrence can be predicted from the tumor stage, grade, and other pathologic features. Advanced risk stratification will likely be possible in the future with increased use of molecular classification and serum biomarkers. Patient comorbidities, age, and individual recurrence risk should also be considered when designing individualized surveillance protocols. SUMMARY: Follow-up after surgery for RCC should focus on imaging of the chest and abdomen to detect common sites of recurrence. Patients should be stratified for risk, and surveillance imaging should be more frequent and intensive in healthy patients with higher risk. Future research is needed to define an optimal individualized surveillance strategy that balances the potential benefits of early cancer detection with the risks and cost of surveillance.

Urinary tract infection-like symptom is associated with worse bladder cancer outcomes in the Medicare population: Implications for sex disparities.

OBJECTIVES: To determine the time to bladder cancer diagnosis from initial infection-like symptoms and its impact on cancer outcomes. METHODS: Using Surveillance, Epidemiology and End Results-Medicare, we designed a retrospective cohort study identifying beneficiaries aged ≥ 66 years diagnosed with bladder cancer from 2007 to 2009. Patients were required to have a hematuria or urinary tract infection claim within 1 year of bladder cancer diagnosis (n = 21 216), and have 2 years of prior Medicare data (n = 18 956) without any precedent hematuria, bladder cancer or urinary tract infection claims (n = 12 195). The number of days to bladder cancer diagnosis was measured, as well as the impact of sex and presenting symptom on time to diagnosis, pathology, and oncological outcomes. RESULTS: The mean time to bladder cancer diagnosis was 72.2 days in women versus 58.9 days in men (P < 0.001). A logistic regression model identified the greatest predictors of ≥ pT2 pathology were both women (odds ratio 2.08, 95% confidence interval 1.70-2.55) and men (odds ratio 1.71, 95% confidence interval 1.49-1.97) presenting with urinary tract infection. Cox proportional hazards analysis identified an increased risk of mortality from bladder cancer and all causes in women presenting with urinary tract infection (hazard ratio 1.37, 95% confidence interval 1.10-1.71, and hazard ratio 1.47, 95% confidence interval 1.28-1.69) compared with women with hematuria. CONCLUSIONS: Women have a longer interval from urinary tract infection to diagnosis of bladder cancer. Urinary tract infection presentation can adversely affect time to diagnosis, pathology and survival. Time to diagnosis seems not to be an independent predictor of bladder cancer outcomes.

Population based analysis of incidence and predictors of open conversion during minimally invasive radical prostatectomy.

PURPOSE: We used population based data to measure the rates and risk factors of open conversion during minimally invasive radical prostatectomy in the United States. MATERIALS AND METHODS: We retrospectively analyzed the records of 87,415 patients in the NCDB who underwent minimally invasive radical prostatectomy between 2010 and 2011. We compared surgical outcomes and treatment facility characteristics between converted and nonconverted cases. Multivariable analysis was done to evaluate conversion risk factors. RESULTS: There were 82,338 robot-assisted (94%) and 5,077 laparoscopic (6%) radical prostatectomies, and 1,080 conversions (1.2%). Fewer robot-assisted cases were converted than laparoscopic cases (0.9% vs 6.5%, p <0.001). The median yearly treatment facility volume of minimally invasive radical prostatectomy was 32 (IQR 10-72). Patients who underwent conversion were more likely to be rehospitalized within 30 days (4.4% vs 2.7%, p = 0.002) and have a postoperative hospital stay of greater than 2 days (40.4% vs 15.1%, p <0.001) than those without conversion. Facilities in the lowest quartile of the yearly volume of the minimally invasive procedure represented 3.8% of minimally invasive radical prostatectomies but accounted for 22.9% of conversions. The second, third and fourth quartiles of yearly treatment facility minimally invasive volume predicted a lower likelihood of conversion compared to the first quartile (each p <0.001). Facility type (eg academic or community) did not predict conversion. Black race (vs white OR 1.52, 95% CI 1.24-1.86, p <0.001) and laparoscopic radical prostatectomy (OR 4.68, 95% CI 3.79-5.78, p <0.001) predicted higher odds of conversion. CONCLUSIONS: Open conversion during minimally invasive radical prostatectomy is a rare event. However, it is significantly more likely for pure laparoscopic surgery, in black men and at low volume facilities. Facility type did not affect conversion rates.

The importance of transurethral resection of bladder tumor in the management of nonmuscle invasive bladder cancer: a systematic review of novel technologies.

PURPOSE: Transurethral bladder tumor resection is one of the most commonly performed procedures by practicing urologists for the diagnosis, staging and treatment of nonmuscle invasive bladder cancer. There is wide variation in the technique and quality of transurethral bladder tumor resection among urologists. This is the first and critically important diagnostic and staging tool in the management of bladder cancer, which is a potentially lethal malignancy and the most costly urological malignancy to manage. In this review we provide an evidence-based rationale for the incorporation of novel technologies for transurethral resection of bladder tumor in the setting of previously set standards. MATERIALS AND METHODS: A systematic MEDLINE®/PubMed®, Cochrane Library and Ovid MEDLINE® search was performed using 2 separate search queries. The MEDLINE/PubMed search was performed using the key words "transurethral resection bladder tumor," filtering the search to include studies published within the last 5 years, English language and human species. A second search without filters was performed with the same key words in the Cochrane Library and Ovid MEDLINE. Study eligibility was defined based on patients with nonmuscle invasive bladder cancer, treatment with transurethral bladder tumor resection and with variable comparators based on novel technology used. All study designs were accepted except case reports, animal studies, editorials and review articles with various outcome measures reported including tumor detection, residual tumor detection, disease recurrence/progression and adverse events. RESULTS: The literature search ultimately yielded 971 manuscripts for review with 42 meeting inclusion criteria for systematic review. Refinements in technique and surgeon experience are critical for the performance of a thorough, complete, high quality transurethral bladder tumor resection. Recent technological advances including bipolar electrocautery and regional anesthetic techniques may help reduce the complications associated with transurethral bladder tumor resection. Photodynamic diagnosis may help increase the diagnostic accuracy, reduce the recurrence rate and decrease the cost of treating patients with nonmuscle invasive bladder cancer. Repeat transurethral bladder tumor resection and perioperative intravesical chemotherapy remain standard components in select patients with nonmuscle invasive bladder cancer. Appropriate clinical staging and treatment of patients with nonmuscle invasive bladder cancer remain a challenge. CONCLUSIONS: Recent advances in transurethral bladder tumor resection should aid its diagnostic accuracy, reduce recurrences, decrease complications and reduce the cost of management of nonmuscle invasive bladder cancer. Urologists should incorporate these evidence-based strategies into current guideline recommendations to improve patient outcomes following transurethral resection of bladder tumor in everyday practice.

Cystectomy and urinary diversion as management of treatment-refractory benign disease: the impact of preoperative urological conditions on perioperative outcomes.

OBJECTIVES: To investigate perioperative outcomes associated with cystectomy and urinary diversion for treatment-refractory benign urological disease. METHODS: A cohort of patients who underwent cystectomy for infection, fistula, bleeding, incontinence, neurogenic bladder or pain between January 2004 and June 2012 was established. Data included baseline demographics, indications for cystectomy and prior treatments, and complications at 30 and 90 days. Primary outcome measures were 30-day and 30 to 90-day complications. RESULTS: The study group comprised eight males and 18 females. The mean age was 57.8 years (95% CI 50.8-64.7). A total of 19 patients (73%) had resolution of their underlying urological pathology at 90 days. A total of 19 patients (73%) experienced a complication in the first 30 days, of which nine (47%) were Clavien grade III or higher. The most common 30-day complications were urinary tract infection (n = 6, 23%) and wound infection (n = 6, 23%). A total of 44% (4/9) of patients with neurogenic bladder experienced a complication within the first 30 days of cystectomy compared with 100% (8/8) of patients with radiation-induced fistula (P = 0.03) and 78% (7/9) of non-neurogenic, non-radiation-induced fistula patients (P = 0.34). CONCLUSIONS: Cystectomy with urinary diversion for benign disease might be successful, but is associated with a high rate of perioperative complications. Those with radiation-induced fistula are more likely to experience complications, whereas those with neurogenic bladder carry a lower risk. Patients should be counseled appropriately regarding expected postoperative outcomes.

Comparison of Work Relative Value Units Assigned to Urological and Gynecological Surgical Procedures.

INTRODUCTION: We sought to determine if work relative value unit differences exist between analogous, sex-specific procedures. METHODS: Representatives from the AUA and the American College of Obstetricians and Gynecologists independently reviewed the entire procedural code set and identified sex-specific procedures that had an analogous procedure in the opposite sex. These pairs were then evaluated and compared using current American Medical Association Relative Value Scale Update Committee methodology. Comparable code pair values were then examined to determine any systemic bias in the work relative value units assigned between the procedures. Mean differences and 95% confidence intervals were used to determine any differences in procedure or physician time values. The methodology used considered global period, intraservice time, total time, hospital days, postoperative office visits, and the date of the committee review. RESULTS: Of the 10 directly analogous code pairs reviewed, 7 of the female procedures had higher work relative value unit differences (range 0.29-6.47), and 3 of the male procedures had higher work relative value unit differences (range 1.23-2.34). There was no statistical difference between the code pair work relative value units. The work relative value unit per minute of intraservice time and total time were not statistically different. CONCLUSIONS: In this study, we compared operative procedures performed in women with clinically comparable operative procedures performed in men that had similar surgical approaches, global periods, and valuation methodologies. Overall, no statistical differences in work relative value units were demonstrated.

Shorter Ureters Lead to Fewer Strictures Following Cystectomy and Urinary Diversion.

OBJECTIVE: To identify the impact of length of distal ureteral resection on the risk of benign uretero-enteric anastomotic stricture (UEAS) formation following cystectomy and urinary diversion. METHODS: A database of patients who underwent cystectomy and urinary diversion from 2015 to 2022 was analyzed. Distal ureteral resections were sent for final pathology. The length of resected ureter was collected from pathology reports. Benign UEAS were confirmed with renal scintigraphy, antegrade nephrostogram, or endoscopic evaluation. The relationship between stricture formation and clinical parameters were assessed using T-tests, chi-square tests, and multivariable analysis. RESULTS: A total of 366 patients underwent cystectomy and urinary diversion. Of the cohort, 35 (9.5%) patients developed UEAS. Median time to stricture formation was 12.5months (IQR 4-30). Of the 711 uretero-enteric anastomoses, 40 (5.6%) ultimately formed a UEAS. Median distal ureteral resection was significantly longer among ureteral anastomoses which did not form a UEAS (2.3 cm vs 1.65 cm, P = .028). Multivariable logistic regression adjusting for surgical approach, prior radiation, ureteral side, and urinary diversion type demonstrated that longer distal ureteral resections were inversely associated with odds of UEAS formation (OR 0.73, 95% CI 0.58-0.92). Multivariable Cox regression analysis similarly showed that length of distal ureteral resection was inversely associated with time to stricture formation (HR 0.78, 95% CI 0.62-0.98). CONCLUSION: The etiology of benign UIA strictures is multifactorial. Vascular compromise is a critical hypothesis. We found that longer distal ureteral resections (and thus shorter ureters) were associated with a significantly lower risk of stricture formation in cystectomy patients.