Catheterization alters bladder ecology to potentiate Staphylococcus aureus infection of the urinary tract.

Methicillin-resistant Staphylococcus aureus (MRSA) is an emerging cause of catheter-associated urinary tract infection (CAUTI), which frequently progresses to more serious invasive infections. We adapted a mouse model of CAUTI to investigate how catheterization increases an individual's susceptibility to MRSA UTI. This analysis revealed that catheterization was required for MRSA to achieve high-level, persistent infection in the bladder. As shown previously, catheter placement induced an inflammatory response resulting in the release of the host protein fibrinogen (Fg), which coated the bladder and implant. Following infection, we showed that MRSA attached to the urothelium and implant in patterns that colocalized with deposited Fg. Furthermore, MRSA exacerbated the host inflammatory response to stimulate the additional release and accumulation of Fg in the urinary tract, which facilitated MRSA colonization. Consistent with this model, analysis of catheters from patients with S. aureus-positive cultures revealed colocalization of Fg, which was deposited on the catheter, with S. aureus Clumping Factors A and B (ClfA and ClfB) have been shown to contribute to MRSA-Fg interactions in other models of disease. We found that mutants in clfA had significantly greater Fg-binding defects than mutants in clfB in several in vitro assays. Paradoxically, only the ClfB- strain was significantly attenuated in the CAUTI model. Together, these data suggest that catheterization alters the urinary tract environment to promote MRSA CAUTI pathogenesis by inducing the release of Fg, which the pathogen enhances to persist in the urinary tract despite the host's robust immune response.

Fibrinogen Release and Deposition on Urinary Catheters Placed during Urological Procedures.

PURPOSE: Catheter associated urinary tract infections account for approximately 40% of all hospital acquired infections worldwide with more than 1 million cases diagnosed annually. Recent data from a catheter associated urinary tract infection animal model has shown that inflammation induced by catheterization releases host fibrinogen, which accumulates on the catheter. Further, Enterococcus faecalis catheter colonization was found to depend on EbpA (endocarditis and biofilm-associated pilus), a fibrinogen binding adhesin. We evaluated this mechanism in a human model. MATERIALS AND METHODS: Urinary catheters were collected from patients hospitalized for surgical or nonsurgical urological procedures. Catheters were subjected to immunofluorescence analyses by incubation with antifibrinogen antibody and then staining for fluorescence. Fluorescence intensity was compared to that of standard catheters. Catheters were incubated with strains of Enterococcus faecalis, Staphylococcus aureus or Candida to assess binding of those strains to fibrinogen laden catheters. RESULTS: After various surgical and urological procedures, 50 catheters were collected. In vivo dwell time ranged from 1 hour to 59 days. All catheters had fibrinogen deposition. Accumulation depended on dwell time but not on surgical procedure or catheter material. Catheters were probed ex vivo with E. faecalis, S. aureus and Candida albicans, which bound to catheters only in regions where fibrinogen was deposited. CONCLUSIONS: Taken together, these data show that urinary catheters act as a binding surface for the accumulation of fibrinogen. Fibrinogen is released due to inflammation resulting from a urological procedure or catheter placement, creating a niche that can be exploited by uropathogens to cause catheter associated urinary tract infections.

Tumor diameter accurately predicts perioperative outcomes in T1 renal cancer treated with robot-assisted partial nephrectomy.

PURPOSE: To compare diameter as a continuous variable with categorical R.E.N.A.L. nephrometry score (RNS) in predicting surgical outcomes of robotic partial nephrectomy (RPN). METHODS: We retrospectively reviewed consecutive patients receiving RPN at our institution between July 2007 and June 2014 (n = 286). Three separate multivariate analyses were performed to assess the relationship between RNS components (R = radius, E = endophyticity, N = nearness to collecting system, L = location relative to polar lines), total RNS, and diameter as a continuous variable with operating time, warm ischemia time (WIT), and estimated blood loss (EBL). Each linear regression model's quality of fit to the data was assessed with coefficients of determination (R 2). RESULTS: Continuous tumor diameter and total RNS were each significantly correlated to operative time, EBL, and WIT (p < 0.001). Categorical R related to operative time (R = 2 vs. R = 1, p = 0.001; R = 3 vs. R = 1, p = 0.001) and WIT (R = 2 vs. R = 1, p = 0.003; R = 3 vs. R = 1, p = 0.016), but not to EBL. For each of these outcomes, diameter outperformed both R and total RNS, as assessed by R 2. Age, body mass index, Charlson Comorbidity Index, and anterior versus posterior location did not correlate with surgical outcomes. CONCLUSIONS: In this series of RPN from a high-volume center, surgical outcomes more closely related to tumor diameter than RNS. While RNS provides surgeons a standardized tool for preoperative planning of renal masses, tumor size may be employed as a more familiar measurement when counseling patients on potential outcomes.

A prospective study of risk factors for nephrolithiasis after Roux-en-Y gastric bypass surgery.

PURPOSE: Roux-en-Y gastric bypass surgery has become an increasingly common form of weight management. Early retrospective reviews have suggested that new onset nephrolithiasis develops in some patients after undergoing Roux-en-Y gastric bypass. We present a prospective longitudinal study to assess risk factors for nephrolithiasis after Roux-en-Y gastric bypass. MATERIALS AND METHODS: A total of 45 morbidly obese patients scheduled to undergo Roux-en-Y gastric bypass surgery were enrolled in this prospective study between November 2006 and November 2007. Exclusion criteria included history of nephrolithiasis or inflammatory bowel disease. Serum uric acid, parathyroid hormone, calcium, albumin, and creatinine and 24-hour urine collections were obtained within 6 months before Roux-en-Y gastric bypass, and at 6 to 12 months postoperatively. A Wilcoxon signed-rank test was used to compare preoperative and postoperative serum laboratory values and 24-hour urine values. McNemar's test was used to determine if the percent of abnormal values underwent a statistically significant change after Roux-en-Y gastric bypass. For both statistical methods a p value was calculated for the change in each variable with p <0.05 considered statistically significant. RESULTS: Statistically significant changes included increased urinary oxalate and calcium oxalate supersaturation, and decreased urinary citrate and total urinary volume postoperatively. A statistically significant percentage of patients exhibited decreased urinary calcium, while a statistically significant percentage of patients experienced increased urinary oxalate and calcium oxalate supersaturation. CONCLUSIONS: Our prospective study demonstrated multiple factors that increase the relative risk of nephrolithiasis after Roux-en-Y gastric bypass. These changes may make stone formation after Roux-en-Y gastric bypass increasingly likely and pose an ongoing challenge in the realm of urology.

Metastatic clear cell renal cell carcinoma to the forearm without identifiable primary renal mass.

Kidney cancer is the ninth most common malignancy in the United States. Most kidney cancers are clear cell renal cell carcinoma (RCC) and arise as solid tumors from kidney parenchyma. In the setting of metastatic disease, a primary renal tumor is usually identified, and metastases are often to lung, bone, liver, and brain. Metastatic RCC without an identifiable solid kidney tumor is exceedingly rare. We report the case of a 52 year old male with a rare cutaneous RCC metastasis without an identifiable primary renal tumor.

Patient-reported quality of life recovery curves after robotic prostatectomy are similar across body mass index categories.

PURPOSE: To assess the impact of body mass index (BMI) on postoperative recovery curve of urinary and sexual function after robotic-assisted laparoscopic prostatectomy (RALP). We hypothesized that overweight and obese men have different recovery curves than normal weight men. MATERIALS AND METHODS: We reviewed preoperative and postoperative surveys from 691 men who underwent RALP from 2004-2014 in an integrated healthcare delivery system. Survey instruments included: sexual health inventory for men (SHIM), urinary behavior, leakage, and incontinence impact questionnaire (IIQ). A repeated measures analysis with autoregressive covariance structure was employed with linear splines with 2 knots for the time factor. We fit unadjusted and adjusted models and stratified by BMI (under/normal weight, overweight, and obese). Adjusted models included age, race/ethnicity, smoking status, diabetes, operation length, prostate-specific antigen, pathologic stage, nerve-sparing status, and surgery year. RESULTS: Mean age was 59 years. Most men were overweight (43%) and obese (42%). There were no significant differences in mean baseline SHIM, urinary behavior, leakage, and IIQ scores by BMI category. All groups had initial steep declines in urinary and sexual function in the first 3 months after RALP. There were no significant differences in postoperative urinary and sexual function score curves by BMI category. CONCLUSIONS: The pattern of urinary and sexual function recovery was similar across all BMI categories. Overweight and obese men may be counseled that urinary and sexual function recovery curves after surgery is similar to that of normal weight men.

Computed Tomography and Magnetic Resonance Findings of Fat-Poor Angiomyolipomas.

INTRODUCTION: Approximately 5% of angiomyolipomas (AMLs) are classified as "fat poor" due to lack of visually detectable fat on imaging, making them difficult to distinguish from renal cell carcinoma. Recent investigations have proposed CT and MR imaging features suggestive of fat-poor AML (fp-AML). Herein, we determined the frequency of these features in a cohort of fp-AMLs by retrospective review of preoperative imaging. METHODS: A pathology database query from January 2005 to August 2013 identified 49 renal specimens of AML with available imaging. A retrospective review of all CT and MR images of these 49 cases was conducted. Cases with visually detectable fat on imaging were excluded. RESULTS: A total of 26 fp-AMLs were identified. Thirteen lesions had available unenhanced CT images, of which eight (62%) were hyperdense compared to the adjacent renal parenchyma, while five (38%) were isodense. Twenty lesions had enhanced CT images: 14 (70%) and 6 (30%) with homogeneous and heterogeneous enhancement, respectively. Of the nine lesions with enhanced MR sequences, five (56%) were homogeneously enhancing, and four (44%) were heterogeneously enhancing. Eight of nine (89%) lesions had hypointense signal intensity (SI) on T2-weighted MR sequences, while one (11%) had hyperintense SI. None of the eight lesions displayed a decrease in signal on fat-suppressed sequences. CONCLUSIONS: In this study, we confirmed common imaging features of fp-AML: high attenuation on unenhanced CT sequences, homogeneous enhancement on CT, and hypointensity on T2-weighted MR. When these features are present, a renal mass biopsy may be prudent.

Evaluation of mechanical bowel preparation methods in urinary diversion surgery.

OBJECTIVES: We performed the first prospective, randomized, multi-center comparison of overall quality and patient tolerability of polyethylene glycol (PEG) and sodium phosphate (NaP) solution for mechanical bowel preparation prior to urinary diversion surgery. METHODS: Between 2001 and 2003, 36 patients at six institutions underwent major urological reconstructive surgery incorporating small intestine (35 radical cystectomy with urinary diversion and 1 bladder augmentation). Patients were prospectively randomized to receive either oral polyethylene glycol (group 1, n = 16) or sodium phosphate (group 2, n = 20) for mechanical bowel preparation prior to surgery, according to our multi-institutional IRB-approved protocol. All patients completed a questionnaire the morning of surgery to assess the tolerability and side effects of each agent. Quality of the bowel preparation was recorded based on intraoperative findings of the attending surgeon, who was blinded to the preparation method. RESULTS: Both bowel cleansing regimens were safe and well tolerated. Patient-reported ease of use and subjective incidence of side effects were statistically similar in the two groups, and a statistically non-significant trend to more bloating in the PEG group was also noted (p = 0.085). Surgeon-scored overall quality of preparation adequacy revealed no significant differences between oral sodium phosphate and polyethylene glycol solutions (p = 0.555). Postoperative complications were rare for each bowel preparation agent. CONCLUSIONS: Performance characteristics of oral sodium phosphate and polyethylene glycol bowel preparations appear to be similar. Each method is safe, efficacious, and well-tolerated when used prior to urinary diversion surgery. The cost for the NaP preparation was $1.40 versus $19.70 for the PEG bowel preparation. Sodium phosphate may have a slight advantage because of its convenience and economic advantage.

Is extended preoperative antibiotic prophylaxis for high-risk patients necessary before percutaneous nephrolithotomy?

PURPOSE: The goal of this study was to compare the rate of systemic inflammatory response syndrome (SIRS) in high-risk patients undergoing percutaneous nephrolithotomy (PCNL) between patients who received 7, 2, or 0 days of preoperative antibiotics. MATERIALS AND METHODS: We retrospectively reviewed a series of consecutive PCNLs performed at our institution. Patients with infected preoperative urine cultures were excluded. High-risk patients were defined as those with a history of previous urinary tract infection (UTI), hydronephrosis, or stone size ≥2 cm. Patients were treated with 7, 2, or 0 days of preoperative antibiotic prophylaxis prior to PCNL. All patients received a single preoperative dose of antibiotics within 60 minutes of the start of surgery. Fisher exact test was used to compare the rate of SIRS by preoperative antibiotic length. RESULTS: Of the 292 patients identified, 138 (47.3%) had sterile urine and met high-risk criteria, of which 27 (19.6%), 39 (28.3%), and 72 (52.2%) received 7, 2, and 0 days of preoperative antibiotics, respectively. The 3 groups were similar in age, sex, and duration of surgery (p>0.05). There was no difference in the rate of SIRS between the groups, with 1 of 27 (3.7%), 2 of 39 (5.1%) and 3 of 72 patients (4.2%) meeting criteria in the 7, 2, and 0 days antibiotic groups (p=~1). CONCLUSIONS: Extended preoperative antibiotic prophylaxis was not found to reduce the risk of SIRS after PCNL in our institutional experience of high-risk patients. For these patients, a single preoperative dose of antibiotics is sufficient.

Patient comorbidity predicts hospital length of stay after robot-assisted prostatectomy.

We sought to examine the impact of baseline patient characteristics and perioperative outcomes on postoperative hospital length of stay (LOS), following the robot-assisted radical prostatectomy (RARP). We retrospectively reviewed consecutive patients receiving RARP at our institution by two surgeons between January 2012 and March 2014 (n = 274). Baseline patient characteristics were collected, including Charlson comorbidity index (CCI). Discharge criteria were identical for all patients and included: return of bowel function, pain controlled with oral medications, and ambulation without assistance. LOS was calculated as the number of midnights spent in the hospital following surgery. Postoperative hospital LOS was equal to 1 day for 225 patients and >1 day for 49 patients. Baseline patient and tumor characteristics, including age, race, body-mass index (BMI), pathologic stage, and Gleason score, were not significantly different. Mean operative time was shorter for patients with LOS > 1 day (155 vs. 173 min, p < 0.01) on univariate analysis. Patients with LOS > 1 day were more likely to have had a complication: 8/49 (17 %) vs. 14/225 (6 %), p < 0.01. However, multivariate logistic regression found baseline CCI > 2 as the only independent predictor of LOS > 1 day (OR = 3.2, p = 0.03), controlling for age, race, BMI, Gleason score, tumor stage, blood loss, operative time, and occurrence of complication. In our experience, baseline patient comorbidity, quantified by CCI, was the only independent predictor of hospital LOS greater than 1 day following RARP. Preoperative assessment of patient comorbidity should be used to better counsel patients on their anticipated postoperative course.

Antibody-Based Therapy for Enterococcal Catheter-Associated Urinary Tract Infections.

Gram-positive bacteria in the genus Enterococcus are a frequent cause of catheter-associated urinary tract infection (CAUTI), a disease whose treatment is increasingly challenged by multiantibiotic-resistant strains. We have recently shown that E. faecalis uses the Ebp pilus, a heteropolymeric surface fiber, to bind the host protein fibrinogen as a critical step in CAUTI pathogenesis. Fibrinogen is deposited on catheters due to catheter-induced inflammation and is recognized by the N-terminal domain of EbpA (EbpANTD), the Ebp pilus's adhesin. In a murine model, vaccination with EbpANTD confers significant protection against CAUTI. Here, we explored the mechanism of protection using passive transfer of immune sera to show that antisera blocking EbpANTD-fibrinogen interactions not only is prophylactic but also can act therapeutically to reduce bacterial titers of an existing infection. Analysis of 55 clinical CAUTI, bloodstream, and gastrointestinal isolates, including E. faecalis, E. faecium, and vancomycin-resistant enterococci (VRE), revealed a diversity of levels of EbpA expression and fibrinogen-binding efficiency in vitro Strikingly, analysis of 10 strains representative of fibrinogen-binding diversity demonstrated that, irrespective of EbpA levels, EbpANTD antibodies were universally protective. The results indicate that, despite diversity in levels of fibrinogen binding, strategies that target the disruption of EbpANTD-fibrinogen interactions have considerable promise for treatment of CAUTI. IMPORTANCE: Urinary catheterization is a routine medical procedure, and it has been estimated that 30 million Foley catheters are used annually in the United States. Importantly, placement of a urinary catheter renders the patient susceptible to developing a catheter-associated urinary tract infection, accounting for 1 million cases per year. Additionally, these infections can lead to serious complications, including bloodstream infection and death. Enterococcus strains are a common cause of these infections, and management of enterococcal infections has been more difficult in recent years due to the development of antibiotic resistance and the ability of strains to disseminate, resulting in a major threat in hospital settings. In this study, we developed an antibiotic-sparing treatment that is effective against diverse enterococcal isolates, including vancomycin-resistant enterococci, during catheter-associated urinary tract infections.