A prospective evaluation of the prostate microbiome in malignant and benign tissue using transperineal biopsy.

BACKGROUND: The link between the prostate microbiome and prostate cancer remains unclear. Few studies have analyzed the microbiota of prostate tissue, and these have been limited by potential contamination by transrectal biopsy. Transperineal prostate biopsy offers an alternative and avoids fecal cross-contamination. We aim to characterize the prostate microbiome using transperineal biopsy. METHODS: Patients with clinical suspicion for prostate cancer who were to undergo transperineal prostate biopsy with magnetic resonance imaging (MRI) fusion guidance were prospectively enrolled from 2022 to 2023. Patients were excluded if they had Prostate Imaging Reporting and Data System lesions with scores ≤ 3, a history of prostate biopsy within 1 year, a history of prostate cancer, or antibiotic use within 30 days of biopsy. Tissue was collected from the MRI target lesions and nonneoplastic transitional zone. Bacteria were identified using 16S ribosomal RNA gene sequencing. RESULTS: Across the 42 patients, 76% were found to have prostate cancer. Beta diversity indices differed significantly between the perineum, voided urine, and prostate tissue. There were no beta diversity differences between cancerous or benign tissue, or between pre- and postbiopsy urines. There appear to be unique genera more abundant in cancerous versus benign tissue. There were no differences in alpha diversity indices relative to clinical findings including cancer status, grade, and risk group. CONCLUSIONS: We demonstrate a rigorous method to better characterize the prostate microbiome using transperineal biopsy and to limit contamination. These findings provide a framework for future large-scale studies of the microbiome of prostate cancer.

F-SHARP: a Phase I/II trial of focal salvage high-dose-rate brachytherapy for Radiorecurrent prostate cancer.

BACKGROUND: Intraprostatic local radiorecurrence (LRR) after definitive radiation is being increasingly identified due to the implementation of molecular positron emission tomography (PET)/computed tomography (CT) imaging for the evaluation of biochemical recurrence. Salvage high-dose rate (HDR) brachytherapy offers a promising local therapy option, with encouraging toxicity and efficacy based on early series. Furthermore, the incorporation of advanced imaging allows for focal HDR to further reduce toxicity to maximise the therapeutic ratio. The objectives of the 'focal salvage HDR brachytherapy for locally recurrent prostate cancer in patients treated with prior radiotherapy' (F-SHARP) trial are to determine the acute and late toxicity and efficacy outcomes of focal salvage HDR brachytherapy for LRR prostate cancer. STUDY DESIGN: The F-SHARP is a multi-institutional two-stage Phase I/II clinical trial of salvage focal HDR brachytherapy for LRR prostate cancer enrolling patients at three centres. ENDPOINTS: The primary endpoint is the acute radiation-related Grade ≥3 Common Terminology Criteria for Adverse Events (CTCAE, version 4.03) genitourinary (GU) and gastrointestinal (GI) toxicity rate, defined as within 3 months of brachytherapy. Secondary endpoints include acute and late CTCAE toxicity, biochemical failure, patterns of clinical progression, disease-specific and overall survival, and health-related quality of life, as measured by the International Prostate Symptom Score and 26-item Expanded Prostate Cancer Index Composite instruments. PATIENTS AND METHODS: Key eligibility criteria include: biopsy confirmed LRR prostate adenocarcinoma after prior definitive radiation therapy using any radiotherapeutic modality, no evidence of regional or distant metastasis, and cT1-3a Nx or N0 prostate cancer at initial treatment. All patients will have multiparametric magnetic resonance imaging and molecular PET/CT imaging if possible. In Stage 1, seven patients will be accrued. If there are two or more GI or GU Grade ≥3 toxicities, the study will be stopped. Otherwise, 17 additional patients will be accrued (total of 24 patients). For Stage 2, the cohort will expand to 62 subjects to study the efficacy outcomes, long-term toxicity profile, quality of life, and compare single- vs multi-fraction HDR. Transcriptomic analysis of recurrence biopsies will be performed to identify potential prognostic and predictive biomarkers.

A prostate biopsy risk calculator based on MRI: development and comparison of the Prospective Loyola University multiparametric MRI (PLUM) and Prostate Biopsy Collaborative Group (PBCG) risk calculators.

OBJECTIVES: To develop and validate a prostate cancer (PCa) risk calculator (RC) incorporating multiparametric magnetic resonance imaging (mpMRI) and to compare its performance with that of the Prostate Biopsy Collaborative Group (PBCG) RC. PATIENTS AND METHODS: Men without a PCa diagnosis receiving mpMRI before biopsy in the Prospective Loyola University mpMRI (PLUM) Prostate Biopsy Cohort (2015-2020) were included. Data from a separate institution were used for external validation. The primary outcome was diagnosis of no cancer, grade group (GG)1 PCa, and clinically significant (cs)PCa (≥GG2). Binary logistic regression was used to explore standard clinical and mpMRI variables (prostate volume, Prostate Imaging-Reporting Data System [PI-RADS] version 2.0 lesions) with the final PLUM RC, based on a multinomial logistic regression model. Receiver-operating characteristic curve, calibration curves, and decision-curve analysis were evaluated in the training and validation cohorts. RESULTS: A total of 1010 patients were included for development (N = 674 training [47.8% PCa, 30.9% csPCa], N = 336 internal validation) and 371 for external validation. The PLUM RC outperformed the PBCG RC in the training (area under the curve [AUC] 85.9% vs 66.0%; P < 0.001), internal validation (AUC 88.2% vs 67.8%; P < 0.001) and external validation (AUC 83.9% vs 69.4%; P < 0.001) cohorts for csPCa detection. The PBCG RC was prone to overprediction while the PLUM RC was well calibrated. At a threshold probability of 15%, the PLUM RC vs the PBCG RC could avoid 13.8 vs 2.7 biopsies per 100 patients without missing any csPCa. At a cost level of missing 7.5% of csPCa, the PLUM RC could have avoided 41.0% (566/1381) of biopsies compared to 19.1% (264/1381) for the PBCG RC. The PLUM RC compared favourably with the Stanford Prostate Cancer Calculator (SPCC; AUC 84.1% vs 81.1%; P = 0.002) and the MRI-European Randomized Study of Screening for Prostate Cancer (ERSPC) RC (AUC 84.5% vs 82.6%; P = 0.05). CONCLUSIONS: The mpMRI-based PLUM RC significantly outperformed the PBCG RC and compared favourably with other mpMRI-based RCs. A large proportion of biopsies could be avoided using the PLUM RC in shared decision making while maintaining optimal detection of csPCa.

Risk of prostate cancer for men with prior negative biopsies undergoing magnetic resonance imaging compared with biopsy-naive men: A prospective evaluation of the PLUM cohort.

BACKGROUND: Men with prior negative prostate biopsies have a lower risk of being diagnosed with prostate cancer in comparison with biopsy-naive men. However, the relative clinical utility of identified lesions on multiparametric magnetic resonance imaging (mpMRI) is uncertain between the 2 settings. METHODS: Patients from the Prospective Loyola University mpMRI (PLUM) Prostate Biopsy Cohort (January 2015 to June 2020) were examined. The detection of any prostate cancer and clinically significant prostate cancer (Gleason score ≥ 3 + 4) was stratified by Prostate Imaging-Reporting and Data System (PI-RADS) scores in the prior negative and biopsy-naive settings. Multivariable logistic regression models (PLUM models) assessed predictors, and decision curve analyses were used to estimate the clinical utility of PI-RADS cutoffs relative to the models. RESULTS: Nine hundred men (420 prior negative patients and 480 biopsy-naive patients) were included. Prior negative patients had lower risks of any prostate cancer (27.9% vs 54.4%) and clinically significant prostate cancer (20.0% vs 38.3%) in comparison with biopsy-naive patients, and this persisted when they were stratified by PI-RADS (eg, PI-RADS 3: 13.6% vs 27.4% [any prostate cancer] and 5.2% vs 15.4% [clinically significant prostate cancer]). The rate of detection of clinically significant prostate cancer was 5.3% among men with prior negative biopsy and PI-RADS ≤ 3. Family history and Asian ancestry were significant predictors among biopsy-naive patients. PLUM models demonstrated a greater net benefit and reduction in biopsies (45.8%) without missing clinically significant cancer in comparison with PI-RADS cutoffs (PI-RADS 4: 34.0%). CONCLUSIONS: Patients with prior negative biopsies had lower prostate cancer detection by PI-RADS score category in comparison with biopsy-naive men. Decision curve analyses suggested that many biopsies could be avoided by the use of the PLUM models or a PI-RADS 4 cutoff without any clinically significant cancer being missed. LAY SUMMARY: Men with a prior negative prostate biopsy had a lower risk of harboring prostate cancer in comparison with those who never had a biopsy. This was true even when patients in each group had similar multiparametric magnetic resonance imaging (mpMRI) findings in terms of Prostate Imaging-Reporting and Data System (PI-RADS)-graded lesions. Decision curve analyses showed that many biopsies could be avoided by the use of the Prospective Loyola University mpMRI prediction models or a PI-RADS 4 cutoff for patients with prior negative biopsies.

Multi-institutional analysis of clinical and imaging risk factors for detecting clinically significant prostate cancer in men with PI-RADS 3 lesions.

BACKGROUND: Most Prostate Imaging-Reporting and Data System (PI-RADS) 3 lesions do not contain clinically significant prostate cancer (CSPCa; grade group ≥2). This study was aimed at identifying clinical and magnetic resonance imaging (MRI)-derived risk fac- tors that predict CSPCa in men with PI-RADS 3 lesions. METHODS: This study analyzed the detection of CSPCa in men who underwent MRI-targeted biopsy for PI-RADS 3 lesions. Multivariable logistic regression models with goodness-of-fit testing were used to identify variables associated with CSPCa. Receiver operating curves and decision curve analyses were used to estimate the clinical utility of a predictive model. RESULTS: Of the 1784 men reviewed, 1537 were included in the training cohort, and 247 were included in the validation cohort. The 309 men with CSPCa (17.3%) were older, had a higher prostate-specific antigen (PSA) density, and had a greater likelihood of an anteriorly located lesion than men without CSPCa (p < .01). Multivariable analysis revealed that PSA density (odds ratio [OR], 1.36; 95% confidence interval [CI], 1.05-1.85; p < .01), age (OR, 1.05; 95% CI, 1.02-1.07; p < .01), and a biopsy-naive status (OR, 1.83; 95% CI, 1.38-2.44) were independently associated with CSPCa. A prior negative biopsy was negatively associated (OR, 0.35; 95% CI, 0.24-0.50; p < .01). The application of the model to the validation cohort resulted in an area under the curve of 0.78. A predicted risk threshold of 12% could have prevented 25% of biopsies while detecting almost 95% of CSPCas with a sensitivity of 94% and a specificity of 34%. CONCLUSIONS: For PI-RADS 3 lesions, an elevated PSA density, older age, and a biopsy-naive status were associated with CSPCa, whereas a prior negative biopsy was negatively associated. A predictive model could prevent PI-RADS 3 biopsies while missing few CSPCas. LAY SUMMARY: Among men with an equivocal lesion (Prostate Imaging-Reporting and Data System 3) on multiparametric magnetic resonance imaging (mpMRI), those who are older, those who have a higher prostate-specific antigen density, and those who have never had a biopsy before are at higher risk for having clinically significant prostate cancer (CSPCa) on subsequent biopsy. However, men with at least one negative biopsy have a lower risk of CSPCa. A new predictive model can greatly reduce the need to biopsy equivocal lesions noted on mpMRI while missing only a few cases of CSPCa.

Systematic versus Targeted Magnetic Resonance Imaging/Ultrasound Fusion Prostate Biopsy among Men with Visible Lesions.

PURPOSE: Multiparametric magnetic resonance imaging (mpMRI)-ultrasound (US) fusion-guided biopsy may improve prostate cancer (PCa) detection and reduce grade misclassification. We compared PCa detection rates on systematic, magnetic resonance imaging-targeted, and combined biopsy with evaluation of important subgroups. MATERIALS AND METHODS: Men with clinical suspicion of harboring PCa from 2 institutions with visible Prostate Imaging-Reporting and Data System (PI-RADSTMv2) lesions receiving mpMRI-US fusion-guided prostate biopsy were included (2015-2020). Detection of PCa was categorized by grade group (GG). Clinically-significant PCa (csPCa) was defined as ≥GG2. Patients were stratified by biopsy setting and PI-RADS. RESULTS: Of 1,236 patients (647 biopsy-naïve) included, 626 (50.6%) harbored PCa and 412 (33.3%) had csPCa on combined biopsy. Detection of csPCa was 27.9% vs 23.3% (+4.6%) and GG1 PCa was 11.3% vs 17.8% (-6.5%) for targeted vs systematic cores. Benefit in csPCa detection was higher in the prior negative than biopsy-naïve setting (+7.8% [p <0.0001] vs +1.7% [p=0.3]) while reduction in GG1 PCa detection remained similar (-5.6% [p=0.0002] vs -7.3% [p=0.0001]). Targeted biopsy showed increased csPCa detection for PI-RADS 5, decrease in GG1 for PI-RADS 3, and both for PI-RADS 4 relative to systematic biopsy. Combined biopsy detected more csPCa (+10.0%) and slightly fewer GG1 PCa (-0.5%) compared to systematic alone. Upgrading to ≥GG2 by targeted biopsy occurred in 9.8% with no cancer and 23.6% with GG1 on systematic biopsy. CONCLUSIONS: Combined biopsy doubled the benefit of targeted biopsy alone in detection of csPCa without increasing GG1 PCa diagnoses relative to systematic biopsy. Utility of targeted biopsy was higher in the prior negative biopsy cohort, but advantages of combined biopsy were maintained regardless of biopsy history.

Imaging Features of Renal Masses to Select Optimal Candidates for Tumor Enucleation Partial Nephrectomy.

PURPOSE OF REVIEW: The goal of this paper was to critically evaluate preoperative findings that optimally select candidates for renal tumor enucleation partial nephrectomy. RECENT FINDINGS: Tumor enucleation has been widely accepted as a management option for patients with chronic kidney disease, hereditary renal cell carcinoma, or multifocal disease. Recent evidence suggests safety and efficacy in the management of routine small renal masses. With recent advances in imaging, the literature for ruling out aggressive renal cell carcinoma and selection for tumor enucleation is robust. As the incidence of renal cell carcinoma rises, partial nephrectomy continues to be the mainstay of treatment for localized renal cell carcinoma. Tumor enucleation maximizes preservation of renal parenchyma without hindering oncologic outcomes. It is important to recognize key tumor radiologic findings which urologists may use to optimize patient selection for tumor enucleation.

Predictors of Recurrence, and Progression-Free and Overall Survival following Open versus Robotic Radical Cystectomy: Analysis from the RAZOR Trial with a 3-Year Followup.

PURPOSE: The RAZOR (Randomized Open versus Robotic Cystectomy) trial revealed noninferior 2-year progression-free survival for robotic radical cystectomy. This update was performed with extended followup for 3 years to determine potential differences between the approaches. We also report 3-year overall survival and sought to identify factors predicting recurrence, and progression-free and overall survival. MATERIALS AND METHODS: We analyzed the per protocol population of 302 patients from the RAZOR study. Cumulative recurrence was estimated using nonbladder cancer death as the competing risk event and the Gray test was applied to assess significance in differences. Progression-free survival and overall survival were estimated by the Kaplan-Meier method and compared with the log rank test. Predictors of outcomes were determined by Cox proportional hazard analysis. RESULTS: Estimated progression-free survival at 36 months was 68.4% (95% CI 60.1-75.3) and 65.4% (95% CI 56.8-72.7) in the robotic and open groups, respectively (p=0.600). At 36 months overall survival was 73.9% (95% CI 65.5-80.5) and 68.5% (95% CI 59.8-75.7) in the robotic and open groups, respectively (p=0.334). There was no significant difference in the cumulative incidence rates of recurrence (p=0.802). Patient age greater than 70 years, poor performance status and major complications were significant predictors of 36-month progression-free survival. Stage and positive margins were significant predictors of recurrence, and progression-free and overall survival. Surgical approach was not a significant predictor of any outcome. CONCLUSIONS: This analysis showed no difference in recurrence, 3-year progression-free survival or 3-year overall survival for robotic vs open radical cystectomy. It provides important prospective data on the oncologic efficacy of robotic radical cystectomy and high level data for patient counseling.

Penile Prosthesis Implantation and Timing Disparities After Radical Prostatectomy: Results From a Statewide Claims Database.

BACKGROUND: Many patients with erectile dysfunction (ED) after radical prostatectomy (RP) improve with conservative therapy but some do not; penile prosthesis implantation rates have been sparsely reported, and have used nonrepresentative data sets. AIM: To characterize rates and timing of penile prosthesis implantation after RP and to identify predictors of implantation using a more representative data set. METHODS: The Healthcare Cost and Utilization Project State Inpatient and State Ambulatory Surgery databases for Florida from 2006 to 2015 were used. Patients undergoing RP (2006-2012) were tracked longitudinally for penile prosthesis implantation. Patient and clinical data were analyzed using multivariable logistic regression. OUTCOMES: The primary outcome was risk-adjusted predictors of prosthesis implantation, and the secondary outcome was predictors of the highest quartile of time between RP and penile prosthesis. RESULTS: Of 29,288 men who had RP, 1,449 (4.9%) patients underwent subsequent prosthesis. The mean time from RP to prosthesis was 2.6 years (median: 2.1; interquartile range [IQR]: 1.2-3.5). Adjusted predictors of prosthesis implantation included open RP (odds ratio [OR]: 1.5, P < .01), African American race (OR: 1.7, P < .01) or Hispanic ethnicity (OR: 3.2, P < .01), and Medicare (OR: 1.4, P < .01) insurance. Oler patients (age >70 years; OR: 0.7, P < .01) and those from the highest income quartile relative to the lowest (OR: 0.8, P < .05) were less likely to be implanted. Adjusted predictors of longer RP-to-implantation time (highest quartile: median: 4.7 years; IQR: 3.9-6.0 years) included open RP (OR: 1.78, P < .01), laparoscopic RP (OR: 4.67, P < .01), Medicaid (OR: 3.03, P < .05), private insurance (OR: 2.57, P < .01), and being in the highest income quartile (OR: 2.52, P < .01). CLINICAL IMPLICATIONS: These findings suggest ED treatment healthcare disparities meriting further investigation; upfront counseling on all ED treatment modalities and close monitoring for conservative treatment failure may reduce lost quality of life years. STRENGTHS & LIMITATIONS: This study is limited by its use of administrative data, which relies on accurate coding and lacks data on ED questionnaires/prior treatments, patient-level cost, and oncologic outcomes. Quartile-based analysis of income and time between RP and prosthesis limits the conclusions that can be drawn. CONCLUSION: Less than 5% of post-RP patients undergo penile prosthesis implantation, with open RP, Medicare, African American race, and Hispanic ethnicity predicting post-RP implantation; living in the wealthiest residential areas predicts lower likelihood of implantation compared to the least wealthy areas. Patients with the longest time between RP and prosthesis are more likely to live in the wealthiest areas or have undergone open/laparoscopic RP relative to robotic RP. Bajic P, Patel PM, Nelson MH, et al. Penile Prosthesis Implantation and Timing Disparities After Radical Prostatectomy: Results From a Statewide Claims Database. J Sex Med 2020;17:1175-1181.

Robot-assisted radical cystectomy versus open radical cystectomy in patients with bladder cancer (RAZOR): an open-label, randomised, phase 3, non-inferiority trial.

BACKGROUND: Radical cystectomy is the surgical standard for invasive bladder cancer. Robot-assisted cystectomy has been proposed to provide similar oncological outcomes with lower morbidity. We aimed to compare progression-free survival in patients with bladder cancer treated with open cystectomy and robot-assisted cystectomy. METHODS: The RAZOR study is a randomised, open-label, non-inferiority, phase 3 trial done in 15 medical centres in the USA. Eligible participants (aged ≥18 years) had biopsy-proven clinical stage T1-T4, N0-N1, M0 bladder cancer or refractory carcinoma in situ. Individuals who had previously had open abdominal or pelvic surgery, or who had any pre-existing health conditions that would preclude safe initiation or maintenance of pneumoperitoneum were excluded. Patients were centrally assigned (1:1) via a web-based system, with block randomisation by institution, stratified by type of urinary diversion, clinical T stage, and Eastern Cooperative Oncology Group performance status, to receive robot-assisted radical cystectomy or open radical cystectomy with extracorporeal urinary diversion. Treatment allocation was only masked from pathologists. The primary endpoint was 2-year progression-free survival, with non-inferiority established if the lower bound of the one-sided 97·5% CI for the treatment difference (robotic cystectomy minus open cystectomy) was greater than -15 percentage points. The primary analysis was done in the per-protocol population. Safety was assessed in the same population. This trial is registered with ClinicalTrials.gov, number NCT01157676. FINDINGS: Between July 1, 2011, and Nov 18, 2014, 350 participants were randomly assigned to treatment. The intended treatment was robotic cystectomy in 176 patients and open cystectomy in 174 patients. 17 (10%) of 176 patients in the robotic cystectomy group did not have surgery and nine (5%) patients had a different surgery to that they were assigned. 21 (12%) of 174 patients in the open cystectomy group did not have surgery and one (1%) patient had robotic cystectomy instead of open cystectomy. Thus, 302 patients (150 in the robotic cystectomy group and 152 in the open cystectomy group) were included in the per-protocol analysis set. 2-year progression-free survival was 72·3% (95% CI 64·3 to 78·8) in the robotic cystectomy group and 71·6% (95% CI 63·6 to 78·2) in the open cystectomy group (difference 0·7%, 95% CI -9·6% to 10·9%; pnon-inferiority=0·001), indicating non-inferiority of robotic cystectomy. Adverse events occurred in 101 (67%) of 150 patients in the robotic cystectomy group and 105 (69%) of 152 patients in the open cystectomy group. The most common adverse events were urinary tract infection (53 [35%] in the robotic cystectomy group vs 39 [26%] in the open cystectomy group) and postoperative ileus (33 [22%] in the robotic cystectomy group vs 31 [20%] in the open cystectomy group). INTERPRETATION: In patients with bladder cancer, robotic cystectomy was non-inferior to open cystectomy for 2-year progression-free survival. Increased adoption of robotic surgery in clinical practice should lead to future randomised trials to assess the true value of this surgical approach in patients with other cancer types. FUNDING: National Institutes of Health National Cancer Institute.

Preclinical efficacy of dual mTORC1/2 inhibitor AZD8055 in renal cell carcinoma harboring a TFE3 gene fusion.

BACKGROUND: Renal cell carcinomas (RCC) harboring a TFE3 gene fusion (TfRCC) represent an aggressive subset of kidney tumors. Key signaling pathways of TfRCC are unknown and preclinical in vivo data are lacking. We investigated Akt/mTOR pathway activation and the preclinical efficacy of dual mTORC1/2 versus selective mTORC1 inhibition in TfRCC. METHODS: Levels of phosphorylated Akt/mTOR pathway proteins were compared by immunoblot in TfRCC and clear cell RCC (ccRCC) cell lines. Effects of the mTORC1 inhibitor, sirolimus, and the dual mTORC1/2 inhibitor, AZD8055, on Akt/mTOR activation, cell cycle progression, cell viability and cytotoxicity were compared in TfRCC cells. TfRCC xenograft tumor growth in mice was evaluated after 3-week treatment with oral AZD8055, intraperitoneal sirolimus and respective vehicle controls. RESULTS: The Akt/mTOR pathway was activated to a similar or greater degree in TfRCC than ccRCC cell lines and persisted partly during growth factor starvation, suggesting constitutive activation. Dual mTORC1/2 inhibition with AZD8055 potently inhibited TfRCC viability (IC50 = 20-50 nM) due at least in part to cell cycle arrest, while benign renal epithelial cells were relatively resistant (IC50 = 400 nM). Maximal viability reduction was greater with AZD8055 than sirolimus (80-90% versus 30-50%), as was the extent of Akt/mTOR pathway inhibition, based on significantly greater suppression of P-Akt (Ser473), P-4EBP1, P-mTOR and HIF1α. In mouse xenograft models, AZD8055 achieved significantly better tumor growth inhibition and prolonged mouse survival compared to sirolimus or vehicle controls. CONCLUSIONS: Akt/mTOR activation is common in TfRCC and a promising therapeutic target. Dual mTORC1/2 inhibition suppresses Akt/mTOR signaling more effectively than selective mTORC1 inhibition and demonstrates in vivo preclinical efficacy against TFE3-fusion renal cell carcinoma.

Socioeconomic and patient-related factors for the management of male urethral stricture disease.

PURPOSE: We sought to determine the socioeconomic and patient factors that influence the utilization of urethroplasty and location of management in the treatment of male urethral stricture disease. METHODS: A retrospective review using the Healthcare Cost and Utilization Project State Inpatient and Ambulatory Surgery and Services Databases for California and Florida was performed. Adult men with a diagnosis of urethral stricture who underwent treatment with urethroplasty or endoscopic dilation/urethrotomy between 2007 and 2011 in California and 2009 and 2014 in Florida were identified by ICD-9 or CPT codes. Patients were categorized based on whether they had a urethroplasty or serial dilations/urethrotomies. Patients were assessed for age, insurance provider, median household income by zip code, Charlson Comorbidity Index, race, prior stricture management, and location of the index procedure. A multivariable logistic regression model was fit to assess factors influencing treatment modality (urethroplasty vs endoscopic management) and location (teaching hospital vs non-teaching hospital). RESULTS: Twenty seven thousand, five hundred and sixty-eight patients were identified that underwent treatment for USD. 25,864 (93.8%) treated via endoscopic approaches and 1704 (6.2%) treated with urethroplasty. Factors favoring utilization of urethroplasty include younger age, lower Charlson Comorbidity score, higher zip code median income quartile, private insurance, prior endoscopic treatment, and management at a teaching hospital. CONCLUSION: Socioeconomic predictors of urethroplasty utilization include higher income status and private insurance. Patient-specific factors influencing urethroplasty were younger age and fewer medical comorbidities. A primary driver of urethroplasty utilization was treatment at a teaching hospital. Older and Hispanic patients were less likely to seek care at these facilities.

Complications of Recognized and Unrecognized Iatrogenic Ureteral Injury at Time of Hysterectomy: A Population Based Analysis.

PURPOSE: Ureteral injury represents an uncommon but potentially morbid surgical complication. We sought to characterize the complications of iatrogenic ureteral injury and assess the effect of recognized vs delayed recognition on patient outcomes. MATERIALS AND METHODS: Patients who underwent hysterectomy were identified in the Healthcare Cost and Utilization Project California State Inpatient Database for 2007 to 2011. Ureteral injuries were identified and categorized as recognized-diagnosed/repaired on the day of hysterectomy and unrecognized-diagnosed/repaired postoperatively. We assessed the outcomes of 90-day hospital readmission as well as 1-year outcomes of nephrostomy tube placement, urinary fistula, acute renal failure, sepsis and overall mortality. The independent effects of recognized and unrecognized ureteral injuries were determined on multivariate analysis. RESULTS: Ureteral injury occurred in 1,753 of 223,872 patients (0.78%) treated with hysterectomy and it was unrecognized in 1,094 (62.4%). The 90-day readmission rate increased from a baseline of 5.7% to 13.4% and 67.3% after recognized and unrecognized injury, respectively. Nephrostomy tubes were required in 2.3% of recognized and 23.4% of unrecognized ureteral injury cases. Recognized and unrecognized ureteral injuries independently increased the risk of sepsis (aOR 2.0, 95% CI 1.2-3.5 and 11.9, 95% CI 9.9-14.3) and urinary fistula (aOR 5.9, 95% CI 2.2-16 and 124, 95% CI 95.7-160, respectively). During followup unrecognized ureteral injury increased the odds of acute renal insufficiency (aOR 23.8, 95% CI 20.1-28.2) and death (1.4, 95% CI 1.03-1.9, p = 0032). CONCLUSIONS: Iatrogenic ureteral injury increases the risk of hospital readmission and significant, potentially life threatening complications. Unrecognized ureteral injury markedly increases these risks, warranting a high level of suspicion for ureteral injury and a low threshold for diagnostic investigation.

Implications of postoperative pulmonary aspiration following major urologic surgery.

INTRODUCTION: The purpose of this article is to assess the incidence of pulmonary aspiration following major urologic surgery, predictors of an aspiration event, and subsequent clinical outcomes. MATERIALS AND METHODS: The Healthcare Cost and Utilization Project State Inpatient Database for California between 2007-2011 was used to identify cystectomy, prostatectomy, partial and radical nephrectomy patients. Aspiration events were identified within 30 days of surgery. The primary outcome was 30 day mortality and secondary outcomes included total length of stay, discharge location, and diagnoses of acute renal failure, pneumonia or sepsis. Descriptive statistics were performed. A multivariable logistic regression was performed to determine independent predictors of an aspiration event. A separate nonparsimonious logistic regression was fit to determine the independent effect of an aspiration event on 30 day mortality. RESULTS: Of 84,837 major urologic surgery patients 319 (0.4%) had an aspiration event. Risk factors for aspiration included ileus, congestive heart failure, paraplegia, chronic lung disease, and age = 80 years (all p < 0.01). Aspiration patients had higher rates of renal failure (36.1% versus 2.5%), pneumonia (36.1% versus 2.5%), sepsis (35.7% versus 0.7%), a prolonged length of stay (17 days versus 3 days), and discharge to nursing facility(26.3% vs 2.3%) (all p<0.001). The 30 day mortality rate following aspiration was 20.7% compared to 0.8% (p < 0.001). Aspiration independently increases the risk of 30 day mortality (OR 3.1 (95%CI 2.2-4.5). CONCLUSIONS: Postoperative aspiration following major urologic surgery is a devastating complication and precautions must be undertaken in high risk patient populations to avoid such an event.

Impact of Post-Hospital Syndrome on Outcomes Following Elective, Ambulatory Surgery.

OBJECTIVE: The aim of this study was to investigate whether post-hospital syndrome (PHS) places patients undergoing elective hernia repair at increased risk for adverse postoperative events. SUMMARY OF BACKGROUND DATA: PHS is a transient period of health vulnerability following inpatient hospitalization for acute illness. PHS has been well studied in nonsurgical populations, but its effect on surgical outcomes is unclear. METHODS: State-specific datasets for California in 2011 available through the Healthcare Cost and Utilization Project (HCUP) were linked. Patients older than 18 years who underwent elective hernia repair were included. The primary exposure variable was PHS, defined as any inpatient admission within 90 days of an elective hernia repair performed in an ambulatory surgery center. The primary outcome was an adverse event, defined as any unplanned emergency department visit or inpatient admission within 30 days postoperatively. Mixed-effects logistic models were used for multivariable analyses. RESULTS: A total of 57,988 patients met inclusion criteria. The 30-day risk-adjusted adverse event rate was significantly higher for PHS patients versus non-PHS patients (11.8% vs 5.8%, P < 0.001). PHS patients were more likely than non-PHS patients to experience postoperative complications (odds ratio 2.2, 95% confidence interval 1.6-3.0). Adverse events attributable to PHS cost an additional $63,533.46 per 100 cases in California. The risk of adverse events due to PHS remained elevated throughout the 90-day window between hospitalization and surgery. CONCLUSIONS: Patients hospitalized within 90 days of an elective surgery are at increased risk of adverse events postoperatively. The impact of PHS on outcomes is independent of baseline patient characteristics, medical comorbidities, quality of center performing the surgery, and reason for hospitalization before elective surgery. Adverse events owing to PHS are costly and represent a quality improvement target.

Rates and Risk Factors for Opioid Dependence and Overdose after Urological Surgery.

PURPOSE: Effective pain management is a critical component of the perioperative process with opioids representing a mainstay of therapy. The opioid epidemic is a growing concern in the United States. The goal of this study was to quantify the risk of opioid dependence or overdose among patients undergoing urological surgery and to identify risk factors of opioid dependence or overdose. MATERIALS AND METHODS: We retrospectively reviewed data on urological surgery from 2007 to 2011. Data sources included the HCUP (Healthcare Cost and Utilization Project) inpatient, ambulatory surgery and emergency department data sets. Outcomes of postoperative opioid dependence and overdose were identified by previously validated ICD-9 codes. Multivariable logistic regression adjusted for surgical procedure was performed to identify predictors of opioid dependence or overdose following urological surgery. RESULTS: Overall 675,527 patients underwent urological surgery, of whom 0.09% were diagnosed with opioid dependence or overdose. Patients in whom opioid dependence or overdose developed were younger (median age 51 vs 62 years), carried nonprivate insurance (69.6% vs 66%), underwent an inpatient procedure (81.0% vs 42.4%) and had a longer length of stay (median 3 vs 0 days) and a history of depression (14.4% vs 3.4%) or chronic obstructive pulmonary disease (20.3% vs 8.9%, all p <0.001). On adjusted multivariable analysis these factors remained independent risk factors for opioid dependence or overdose. CONCLUSIONS: Postoperative opioid dependence or overdose affects 1 of 1,111 urological surgery patients. Risk factors for opioid dependence or overdose included younger age, inpatient surgery and increasing hospitalization duration, baseline depression, tobacco use and chronic obstructive pulmonary disease as well as insurance provider, including Medicaid, Medicare (age less than 65 years) and noninsured status.

Postoperative Urinary Retention is an Independent Predictor of Short-Term and Long-Term Future Bladder Outlet Procedure in Men.

PURPOSE: Postoperative urinary retention is a common complication across surgical specialties. To our knowledge no literature to date has examined postoperative urinary retention as a predictor of long-term receipt of surgery for bladder outlet obstruction. MATERIALS AND METHODS: We retrospectively reviewed the records of inpatients who underwent nonurological surgery in California between 2008 and 2010. Postoperative urinary retention during the index admission was identified, as was receipt of a bladder outlet procedure (transurethral prostate resection, prostate photoselective vaporization or suprapubic prostatectomy) at a subsequent encounter. Patients were matched using propensity scoring of demographics, comorbidities and surgery type. Adjusted Kaplan-Meier analysis was performed to determine the cumulative incidence of subsequent bladder outlet procedures by patient group, including group 1-age 60 years or greater and postoperative urinary retention, group 2-age 60 years or greater and no postoperative urinary retention, group 3-age less than 60 years and postoperative urinary retention, and group 4-age less than 60 years and no postoperative urinary retention. RESULTS: Of 769,141 eligible male patients postoperative urinary retention developed in 8,051 (1.1%). Following hospital discharge 1,855 patients (0.24%) underwent a bladder outlet procedure. Those treated with a bladder outlet procedure were significantly more likely to have experienced postoperative urinary retention during the index admission (6.3% vs 1.0%, p <0.001). On matched analysis the bladder outlet procedure rate at 3 years was 7.1%, 2.2%, 0.8% and 0.0% in groups 1, 2, 3 and 4, respectively. CONCLUSIONS: In men 60 years old or older postoperative urinary retention identified those with an increased incidence of bladder outlet procedures within 3 years. Men younger than 60 years had a low rate of subsequent bladder outlet procedures regardless of a postoperative urinary retention diagnosis.

Standardized Reporting of Microscopic Renal Tumor Margins: Introduction of the Renal Tumor Capsule Invasion Scoring System.

PURPOSE: Renal tumor enucleation allows for maximal parenchymal preservation. Identifying pseudocapsule integrity is critically important in nephron sparing surgery by enucleation. Tumor invasion into and through the capsule may have clinical implications, although it is not routinely commented on in standard pathological reporting. We describe a system to standardize the varying degrees of pseudocapsule invasion and identify predictors of invasion. MATERIALS AND METHODS: We performed a multicenter retrospective review between 2002 and 2014 at Indiana University Hospital and Loyola University Medical Center. A total of 327 tumors were evaluated following removal via radical nephrectomy, standard margin partial nephrectomy or enucleation partial nephrectomy. Pathologists scored tumors using our i-Cap (invasion of pseudocapsule) scoring system. Multivariate analysis was done to determine predictors of higher score tumors. RESULTS: Tumor characteristics were similar among surgical resection groups. Enucleated tumors tended to have thinner pseudocapsule rims but not higher i-Cap scores. Rates of complete capsular invasion, scored as i-Cap 3, were similar among the surgical techniques, comprising 22% of the overall cohort. Papillary histology along with increasing tumor grade was predictive of an i-Cap 3 score. CONCLUSIONS: A capsule invasion scoring system is useful to classify renal cell carcinoma pseudocapsule integrity. i-Cap scores appear to be independent of surgical technique. Complete capsular invasion is most common in papillary and high grade tumors. Further work is warranted regarding the relevance of capsular invasion depth as it relates to the oncologic outcome for local recurrence and disease specific survival.

Discordance between surgical care improvement project adherence and postoperative outcomes: implications for new Joint Commission standards.

BACKGROUND: Infectious (INF) and venous thromboembolism (VTE) complication rates are targeted by surgical care improvement project (SCIP) INF and SCIP VTE measures. We analyzed how adherence to SCIP INF and SCIP VTE affects targeted postoperative outcomes (wound complication [WC], deep vein thrombosis, and pulmonary embolism [PE]) using all-payer data. MATERIALS AND METHODS: A retrospective review (2007-2011) was conducted using Healthcare Cost and Utilization Project State Inpatient Database Florida and Medicare's Hospital Compare. The association between SCIP adherence rates and outcomes across 355 included surgical procedures was measured using multilevel mixed-effects linear regression models. RESULTS: One hundred sixty acute care hospitals and 779,922 patients were included. Over 5 y, SCIP INF-1, -2, and -3 adherence improved by 12.5%, 8.0%, and 20.9%, respectively, whereas postoperative WC rate decreased by 14.8%. When controlling for time, SCIP INF-1 adherence was associated with improvement of postoperative WC rates (ß = -0.0044, P = 0.005), whereas SCIP INF-2 adherence was associated with increased WCs (ß = 0.0031, P = 0.018). SCIP VTE-1, -2 adherence improved by 14.6% and 20.2%, respectively, whereas postoperative deep vein thrombosis rate increased by 7.1% and postoperative PE rate increased by 3.7%. SCIP VTE-1 and -2 adherence were both associated with increased postoperative PE when controlling for time (SCIP VTE-1: ß = 0.0019, P < 0.001; SCIP VTE-2: ß = 0.0015, P < 0.001). Readmission analysis found SCIP INF-1 adherence to be associated with improved 30-d WC rates when controlling for patient and hospital characteristics (ß = -0.0021, P = 0.032), whereas SCIP INF-3 adherence was associated with increased 30-d WC rates when controlling for time (ß = 0.0007, P = 0.04). CONCLUSIONS: Only SCIP INF-1 adherence was associated with improved outcomes. The Joint Commission has retired SCIP INF-2, -3, and SCIP VTE-2 and made SCIP INF-1 and VTE-1 reporting optional. Our study supports continued reporting of SCIP INF-1.

Alcohol inhibits osteopontin-dependent transforming growth factor-ß1 expression in human mesenchymal stem cells.

Alcohol (EtOH) intoxication is a risk factor for increased morbidity and mortality with traumatic injuries, in part through inhibition of bone fracture healing. Animal models have shown that EtOH decreases fracture callus volume, diameter, and biomechanical strength. Transforming growth factor ß1 (TGF-ß1) and osteopontin (OPN) play important roles in bone remodeling and fracture healing. Mesenchymal stem cells (MSC) reside in bone and are recruited to fracture sites for the healing process. Resident MSC are critical for fracture healing and function as a source of TGF-ß1 induced by local OPN, which acts through the transcription factor myeloid zinc finger 1 (MZF1). The molecular mechanisms responsible for the effect of EtOH on fracture healing are still incompletely understood, and this study investigated the role of EtOH in affecting OPN-dependent TGF-ß1 expression in MSC. We have demonstrated that EtOH inhibits OPN-induced TGF-ß1 protein expression, decreases MZF1-dependent TGF-ß1 transcription and MZF1 transcription, and blocks OPN-induced MZF1 phosphorylation. We also found that PKA signaling enhances OPN-induced TGF-ß1 expression. Last, we showed that EtOH exposure reduces the TGF-ß1 protein levels in mouse fracture callus. We conclude that EtOH acts in a novel mechanism by interfering directly with the OPN-MZF1-TGF-ß1 signaling pathway in MSC.