Metabolic syndrome and the urinary microbiome of patients undergoing percutaneous nephrolithotomy.

Objective: To identify possible stone-promoting microbes, we compared the profiles of microbes grown from stones of patients with and without metabolic syndrome (MetS). The association between MetS and urinary stone disease is well established, but the exact pathophysiologic relationship remains unknown. Recent evidence suggests urinary tract dysbiosis may lead to increased nephrolithiasis risk. Methods: At the time of percutaneous nephrolithotomy, bladder urine and stone fragments were collected from patients with and without MetS. Both sample types were subjected to expanded quantitative urine culture (EQUC) and 16 S ribosomal RNA gene sequencing. Results: Fifty-seven patients included 12 controls (21.1%) and 45 MetS patients (78.9%). Both cohorts were similar with respect to demographics and non-MetS comorbidities. No controls had uric acid stone composition. By EQUC, bacteria were detected more frequently in MetS stones (42.2%) compared to controls (8.3%) (p=0.041). Bacteria also were more abundant in stones of MetS patients compared to controls. To validate our EQUC results, we performed 16 S ribosomal RNA gene sequencing. In 12/16 (75.0%) sequence-positive stones, EQUC reliably isolated at least one species of the sequenced genera. Bacteria were detected in both "infectious" and "non-infectious" stone compositions. Conclusion: Bacteria are more common and more abundant in MetS stones than control stones. Our findings support a role for bacteria in urinary stone disease for patients with MetS regardless of stone composition.

Impact of intravesical Bacillus Calmette-Guérin and chemotherapy on the bladder microbiome in patients with non-muscle invasive bladder cancer.

Introduction: Intravesical therapy (IVT), including Bacillus Calmette-Guérin (BCG), is the standard of care for high grade (HG) non-muscle invasive bladder cancer (NMIBC). Despite the use of IVT, many patients recur after treatment. The bladder microbiome and its role in disease processes has recently risen to prominence. We aim to characterize changes that occur in the bladder microbiome over the course of intravesical therapy and assess whether these changes correlate with outcomes in patients with NMIBC. Methods: Patients with NMIBC undergoing induction BCG or intravesical therapy were prospectively enrolled from January 2019 to March 2020. Patients with clinical T2 or greater pathology or active urinary tract infection at enrollment were excluded. Twenty-nine patients had catheterized (bladder) urine samples collected prior to induction intravesical therapy and prior to each IVT instillation. Twenty-seven received BCG while 2 received intravesical gemcitabine. Bacteria were identified using 16S ribosomal RNA gene sequencing. Bladder microbiome changes were evaluated and differences between patients who recurred and patients who did not recur after IVT were investigated. Results: Across the 29 patients analyzed, bacterial richness decreased significantly following intravesical therapy (Richness, P=0.01). Evenness and overall diversity did not change significantly (Pielou, P=0.62; Shannon, P=0.13). Patients who experienced recurrence had a higher relative abundance of Aerococcus in their urine (P<0.01), while those who did not recur had significantly more Ureaplasma (P=0.01) and Escherichia/Shigella species (P=0.05). Patients with decreased levels of alpha diversity were more likely to fall within the non-recurrence cohort. Conclusion: IVT for NMIBC appears to change the urinary microbiome by decreasing richness while not altering evenness or overall diversity. The presence of Aerococcus species may be predictive of a poor cancer response to IVT, while the presence of Ureaplasma and Escherichia/Shigella may predict a favorable response to IVT. Further studies are warranted to elucidate and confirm the significance of changes in the bladder microbiome.

African American Men have Increased Risk of Prostate Cancer Detection Despite Similar Rates of Anterior Prostatic Lesions and PI-RADS Grade on Multiparametric Magnetic Resonance Imaging.

OBJECTIVE: To determine whether the frequency of anterior prostate lesions (APL) on multiparametric magnetic resonance imaging (mpMRI) prior to biopsy differed between African American (AA) and non-AA men and evaluate implications of race and tumor location for prostate cancer (PCa) detection. METHODS: Patients from the Prospective Loyola University mpMRI (PLUM) Prostate Biopsy Cohort (January 2015-December 2020) without prior diagnosis of PCa were evaluated for APLs by race. Multivariable logistic regression models evaluated predictors of APLs and associations of APLs and race with detection of any PCa (grade group 1+) and clinically significant PCa (csPCa; grade group 2+). Additional stratified and propensity score matched analyses were conducted. RESULTS: Of 1,239 men included, 190 (15.3%) were AA and 302 (24.4%) had at least one APL with no differences by race on multivariable analysis. While men with APLs were twice as likely to harbor PCa or csPCa, the unadjusted proportion of targeted biopsy-confirmed APL PCa (12.6% vs 12.0%) or csPCa (8.4% vs 8.9%) were similar for AA and non-AA men. AA men had higher risk of prostate cancer on targeted cores (OR 1.66 (95%CI 1.06 - 2.61), P = 0.026) which was independent of lesion location or PI-RADS. CONCLUSION: AA men were found to have similar rates of APLs on mpMRI to non-AA men indicating access to mpMRI may mitigate some of the historical racial disparity based on lesion location. AA men have increased risk of PCa detection compared to non-AA men independent of anterior location or lesion grade on mpMRI reinforcing the importance of identifying genetic, biologic, and socioeconomic drivers.

Four versus 3 Cycles of Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer: Implications for Pathological Response and Survival.

PURPOSE: The ideal number of neoadjuvant chemotherapy (NAC) cycles for muscle-invasive bladder cancer is uncertain with 3 to 4 representing the standard of care (SOC). We compared ypT0 rates and survival between patients receiving 4 versus 3 cycles of NAC with evaluation of chemotherapy-related toxicity for correlation with tumor chemosensitivity and pathological response. MATERIALS AND METHODS: Patients receiving NAC followed by radical cystectomy for cT2-4N0M0 urothelial carcinoma from 2 institutions were included. Primary study groups included 4 cisplatin-based NAC cycles, 3 cisplatin-based NAC cycles, and nonSOC NAC (1-2 cycles or noncisplatin-based) to compare ypT0/≤ypT1 rates and survival. A cohort of patients not receiving NAC was included for pathological reference. RESULTS: Of 693 total patients, 318 (45.9%) received NAC. ypT0 and ≤ypT1 rates were 42/157 (26.8%) and 86/157 (54.8%) for 4 cycles, 38/114 (33.3%) and 71/114 (62.3%) for 3 cycles, and 6/47 (12.8%) and 13/47 (27.7%) for nonSOC (p=0.03 and p <0.01, respectively). Pathological response appeared higher among patients receiving 3 cycles due to toxicity (ypT0: 29/77 [37.7%]; ≤ypT1: 51/77 [66.2%]) but did not reach statistical significance. Toxicities leading to treatment modifications were thrombocytopenia (32.1%), neutropenia (27.2%), renal insufficiency (22.2%), and constitutional symptoms (18.5%). NonSOC patients had lower Kaplan-Meier survival (cT2-cT4N0M0: log-rank p=0.07; cT2N0M0: log-rank p=0.02). There were no statistically significant differences in survival between 4 and 3 cycles (HR 1.00 [95% CI 0.57-1.74], p=0.99). CONCLUSIONS: Patients completing 3 cycles of cisplatin-based NAC have similar pathologic response and short-term survival compared to 4 cycles. Further evaluation of patients experiencing toxicity as a potential marker of tumor chemosensitivity is needed.

Bridging the Telemedicine Gap Among Seniors During the COVID-19 Pandemic.

At the onset of the COVID-19 pandemic, many senior patients in the USC-Keck Family Medicine clinics were limited or lacking in telemedicine participation. Three factors contributed: lack of video-enabled devices, technological literacy, and/or absence of Wi-Fi connectivity. We addressed the first 2 of these factors. Via phone contact, 9 patients agreed to receive donated Android or Apple devices and to trial instruction manuals for use. Donated equipment and instructions were prepared and delivered in accordance with pandemic guidelines. Follow-up calls indicated that 4 participants were able to set up their devices and 3 of whom had connected with their providers. The remaining 5 participants had not set up their devices by the end of the follow-up period, had difficulty with device setup, accessing applications necessary for telemedicine, or had limited access to Wi-Fi. This project highlights some telemedicine barriers that senior patients may overcome with the additional support of care providers.

Near-infrared Fluorescence Imaging of Ureters With Intravenous Indocyanine Green During Radical Cystectomy to Prevent Ureteroenteric Anastomotic Strictures.

OBJECTIVE: To determine whether intraoperative near-infrared fluorescence imaging of the distal ureter using intravenous indocyanine green (ICG) could provide assessment of vascular adequacy and potentially decrease the risk of ureteroenteric anastomotic stricture (UAS). METHODS: A retrospective chart review was performed of all patients undergoing open radical cystectomy by a single surgeon over a 2-year period. Patients were divided into ICG and non-ICG cohorts based on utilization of ICG. For the ICG group, adequacy of ureteral perfusion was based on visual inspection and the ureter was cut back proximally accordingly prior to anastomosis. Follow-up encounters were reviewed to determine development of benign UAS. RESULTS: A total of 30 and 31 patients were in the non-ICG and ICG cohorts, respectively. There were no differences in baseline demographic and operative data including operative time. Median follow-up was 23.2 months (interquartile range [IQR] 7-29.3) in the non-ICG group compared to 15.8 months (IQR 12.2-18.1) in the ICG group. In the non-ICG cohort, 5 of 30 (16.7%) patients were diagnosed with UAS compared to 1 of 31 (3.2%) in the ICG cohort. The median time to stricture formation for non-ICG cohort was 5.7 months (IQR 3.6-6.6) compared to 7.5 months in the ICG cohort. CONCLUSION: The use of near-infrared fluorescence imaging with intravenous ICG to assess ureteral vascularity prior to ureteroenteric anastomosis may reduce the risk of UAS.

Optimal Cystectomy Outcome: A Composite Measurement Evaluating Quality of Care and Mortality Benefit.

OBJECTIVES: To evaluate the incidence and impact of an "optimal cystectomy outcome" (OCO), a simplified performance metric that encompasses multiple patient-centered outcomes. METHODS: We identified patients in the National Cancer Center Database undergoing radical cystectomy for stage cT2-cT3 urothelial carcinoma (2006-2014). OCO was defined as negative resection margin, adequate lymphadenectomy (>10 nodes), no prolonged length-of-stay (<75th percentile), no 30-day-readmission, and no 30-day-mortality. We used multivariable logistic regression and Cox proportional-hazards models to identify factors associated with OCO and overall survival (OS). RESULTS: Among 12,997 patients who fit the inclusion criteria, individual OCO components were attained at a relatively high rate; however, only 37.6% of patients met all 5 OCO criteria. Patients who underwent surgery at a high-volume (OR 2.45) academic facility (OR 1.60) using a minimally-invasive approach (OR 1.32) were more likely to receive an OCO. Patients were less likely to receive an OCO if they were older (OR 0.98), African American (OR 0.71), had Medicaid insurance (OR 0.66), or more comorbidities (OR 0.48) (all P <0.05). Patients who received an OCO were found to have a significantly lower risk of overall mortality (HR 0.69, P <0.05). CONCLUSION: Various patient- and hospital-specific factors affect a system's ability to achieve OCO in patients undergoing radical cystectomy. OCO is directly associated with improved OS and has the potential to function as a composite performance metric for the quality of care in bladder cancer.

Implications of the Genitourinary Microbiota in Prostatic Disease.

PURPOSE OF REVIEW: To summarize recent investigation into associations between the genitourinary microbiota and prostatic disease. RECENT FINDINGS: The genitourinary tract is not sterile. There are microbial communities (microbiota) in each niche of the genitourinary tract including the bladder, prostate, and urethra, which have been the subject of increasing scientific interest. Investigators have utilized several unique methods to study them, resulting in a highly heterogeneous body of literature. To characterize these genitourinary microbiota, diverse clinical specimens have been analyzed, including urine obtained by various techniques, seminal fluid, expressed prostatic secretions, and prostatic tissue. Recent studies have attempted to associate the microbiota detected from these samples with urologic disease and have implicated the genitourinary microbiota in many common conditions, including benign prostatic hyperplasia (BPH), prostate cancer, and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). In this review, we summarize the recent literature pertaining to the genitourinary microbiota and its relationship to the pathophysiology and management of three common prostatic conditions: BPH, prostate cancer, and CP/CPPS.

Urothelial Carcinoma Recurrence in an Orthotopic Neobladder without Urethral or Upper Urinary Tract Involvement.

We describe a case of a 71-year-old male with an isolated recurrence of urothelial carcinoma in an ileal neobladder without involvement of the upper urinary tract or urethra. He was diagnosed with high grade urothelial carcinoma involving a bladder diverticulum with associated carcinoma in situ. He underwent a radical cystectomy and orthotopic Studer ileal neobladder. On routine follow-up, 11 years following cystectomy, voided urine cytology was positive for high grade urothelial carcinoma. Further workup revealed normal upper urinary tracts, normal urethra, and a solitary lesion at the left anteroinferior wall of the neobladder. He subsequently underwent resection of the neobladder and conversion to an ileal conduit with pathology confirming the diagnosis of high grade urothelial carcinoma. Isolated recurrence of urothelial carcinoma within a neobladder without involvement of the upper urinary tract or urethra is rare. No guidelines exist regarding its management. Herein we present our management as well as the current literature published on this topic.

Concomitant Left Atrial Reduction in Rheumatic Mitral Valve Disease With Giant Left Atrium: Our Technique With Midterm Results.

OBJECTIVE: The giant left atrium is a frequent finding with rheumatic heart disease. The enlarged left atrium was found to be a risk factor for early mortality and postoperative higher thromboembolic events, but its management remains controversial. Most of the surgeons just do the mitral valve procedure without any intervention for enlarged left atrium. We present our center's experience of patients with giant left atrium who underwent a newer technique of left atrium reduction concomitant with mitral valve procedure. METHODS: Between January 2012 and February 2015, 25 patients, who underwent surgery for concomitant left atrium reduction with mitral valve disease, were included in the study after institute's ethics committee clearance. Patients having combined aortic and mitral valve disease were excluded. Preoperative, intraoperative, and postoperative data were collected. All the patients were also followed up clinically and echocardiographically in postoperative period. RESULTS: There were 15 (60%) females. The mean ± SD age of the patients was 36.92 ± 5.4 years. Preoperatively, all patients were in long-standing persistent atrial fibrillation. The mean ± SD bypass and aortic cross-clamp time were 74.56 ± 3.85 and 51.72 ± 4.32 minutes, respectively. There was a significant reduction of left atrium diameter and volume from 94.48 ± 11.0 mm to 40.08 ± 1.35 mm and 348.3 ± 121.1 to 26.57 ± 2.9 mL/m, respectively. There was no early or late mortality. At a mean ± SD follow-up of 42.28 ± 12.1 months, all patients were in New York Heart Association I or II class and 24 (96%) patients were in normal sinus rhythm. CONCLUSIONS: Concurrent left atrium reduction with mitral valve procedure is a feasible and effective technique for event-free survival of the patients having giant left atrium with mitral disease.

Direct Femoral Cannulation in Minimal Invasive Pediatric Cardiac Surgery: Our Experience With Midterm Result.

OBJECTIVE: One of the major challenges faced in minimally invasive pediatric cardiac surgery is cannulation strategy for cardiopulmonary bypass. Central aortic cannulation through the same incision has been the usual strategy, but it has the disadvantage of cluttering of the operative field. We hereby present the results of femoral cannulation in minimally invasive pediatric cardiac surgery in terms of adequacy and safety. METHODS: From January 2013 to June 2016, 200 children (122 males) with mean ± SD age of 9.2 ± 4.51 years (median = 6 years, range = 3-18 years) and weight of 19.22 ± 8.49 kg (median = 15 kg, range = 8-45 kg) were operated for congenital cardiac defects through anterolateral thoracotomy. The most common diagnosis was atrial septal defect (144 patients). In all the patients, femoral artery and femoral vein were cannulated along with direct superior vena cava cannulation for institution of cardiopulmonary bypass. RESULTS: There were no deaths or any major complications related to femoral cannulation. Femoral artery cannulation provided adequate arterial inflow, whereas femoral vein with direct superior vena cava cannulation provided adequate venous return in all the patients. No patient required vacuum-assisted venous drainage. No patient required conversion to sternotomy or developed vascular, neurological complications. At discharge and at 1-year follow-up, both femoral artery and vein were patent without a significant stenosis on color Doppler ultrasonography in all the patients. At mean ± SD follow-up period of 30.63 ± 10.09 months, all the patients were doing well without any wound-related, neurological, or vascular complications. CONCLUSIONS: Femoral arterial and venous cannulation is a feasible, reliable, and efficient method for institution of cardiopulmonary bypass in minimally invasive pediatric cardiac surgery.