Inflammatory bowel disease induces inflammatory and pre-neoplastic changes in the prostate.

BACKGROUND: Inflammatory bowel disease (IBD) has been implicated as a risk factor for prostate cancer, however, the mechanism of how IBD leads to prostate tumorigenesis is not known. Here, we investigated whether chronic intestinal inflammation leads to pro-inflammatory changes associated with tumorigenesis in the prostate. METHODS: Using clinical samples of men with IBD who underwent prostatectomy, we analyzed whether prostate tumors had differences in lymphocyte infiltrate compared to non-IBD controls. In a mouse model of chemically-induced intestinal inflammation, we investigated whether chronic intestinal inflammation could be transferred to the wild-type mouse prostate. In addition, mouse prostates were evaluated for activation of pro-oncogenic signaling and genomic instability. RESULTS: A higher proportion of men with IBD had T and B lymphocyte infiltration within prostate tumors. Mice with chronic colitis showed significant increases in prostatic CD45 + leukocyte infiltration and elevation of three pro-inflammatory cytokines-TIMP-1, CCL5, and CXCL1 and activation of AKT and NF-kB signaling pathways. Lastly, mice with chronic colitis had greater prostatic oxidative stress/DNA damage, and prostate epithelial cells had undergone cell cycle arrest. CONCLUSIONS: These data suggest chronic intestinal inflammation is associated with an inflammatory-rich, pro-tumorigenic prostatic phenotype which may explain how gut inflammation fosters prostate cancer development in men with IBD.

Prior Placement of Male Urethral Slings Can Increase the Need for Revision of Artificial Urinary Sphincters.

BACKGROUND: Recurrent stress urinary incontinence (SUI) following male sling can be managed surgically with artificial urinary sphincter (AUS) insertion. Prior small, single-center retrospective studies have not demonstrated an association between having failed a sling procedure and worse AUS outcomes. The aim of this study was to compare outcomes of primary AUS placement in men who had or had not undergone a previous sling procedure. METHODS: A retrospective review of all AUS devices implanted at a single academic center during 2000-2018 was performed. After excluding secondary AUS placements, revision and explant procedures, 135 patients were included in this study, of which 19 (14.1%) patients had undergone prior sling procedures. RESULTS: There was no significant difference in demographic characteristics between patients undergoing AUS placement with or without a prior sling procedure. Average follow up time was 28.0 months. Prior sling was associated with shorter overall device survival, with an increased likelihood of requiring revision or replacement of the device (OR 4.2 (1.3-13.2), p = 0.015) as well as reoperation for any reason (OR 3.5 (1.2-9.9), p = 0.019). While not statistically significant, patients with a prior sling were more likely to note persistent incontinence at most recent follow up (68.8% vs. 42.7%, p = 0.10). CONCLUSIONS: Having undergone a prior sling procedure is associated with shorter device survival and need for revision or replacement surgery. When considering patients for sling procedures, patients should be counseled regarding the potential for worse AUS outcomes should they require additional anti-incontinence procedures following a failed sling.

Surgeon Scorecards Improve Muscle Sampling on Transurethral Resection of Bladder Tumor and Recurrence Outcomes in Patients with Nonmuscle Invasive Bladder Cancer.

PURPOSE: The presence of detrusor muscle is essential for accurate staging of T1 cancers. Detrusor muscle presence can be a quality indicator of transurethral resection of bladder tumor for nonmuscle invasive bladder cancer. We hypothesized that increasing surgeon awareness of personal and institutional detrusor muscle sampling rates could improve resection quality and long-term oncologic outcomes. MATERIALS AND METHODS: A retrospective review of transurethral resections of bladder tumor from 1/2006 to 2/2018 was performed. The presence of detrusor muscle in the pathology report and transurethral resection specimen were extracted from records. Individual surgeon scorecards were created and distributed. Rates of detrusor muscle sampling were compared prior to and 12 months after distribution. Chart review was done to compare 3-year recurrence and progression outcomes before and after distribution of scorecards. RESULTS: The rate of detrusor muscle sampling increased from 36% (1,250/3,488) to 54% (202/373) (p=0.001) in the 12 months after scorecard distribution, ie from 30% (448/1,500) to 55% (91/165) (p <0.001) in Ta tumors and from 47% (183/390) to 72% (42/58) (p <0.001) in T1 tumors. Pathological reporting of muscle also improved for all samples (73%, 2,530/3,488 to 90%, 334/373, p <0.001), Ta (75%, 1,127/1,500 to 94%, 155/165, p <0.001) and T1 (93%, 362/390 to 100%, 58/58, p=0.04). On multivariate Cox regression analysis, the surgeon scorecard was associated with decreased 3-year risk of recurrence (HR 0.63, 95% CI 0.40-0.99). CONCLUSIONS: Creation and distribution of individual surgeon scorecards improved detrusor muscle sampling on transurethral resection and was associated with decreased risk of disease recurrence. Quality evaluation of transurethral resection of bladder tumor may contribute to improved outcomes of patients with nonmuscle invasive bladder cancer.

Algorithms to Enhance Empiric Antimicrobial Choice for Outpatients With Afebrile Complicated Cystitis Reflects Importance of Status of the Urinary Tract and Patient Place of Residence.

OBJECTIVE: To determine predictive factors for antimicrobial resistance patterns and to develop an antimicrobial treatment algorithm for afebrile outpatients presenting with complicated cystitis. MATERIALS AND METHODS: We performed a retrospective, single-center, cross-sectional study of 2,891 outpatients with a diagnosed afebrile complicated cystitis from 2012 to 2018. For patients with confirmed urinary tract infection and antimicrobial sensitivities, univariate analyses and multivariable regression models were used to determine odds ratios for predicting resistance to trimethoprim-sulfamethoxazole, ciprofloxacin, nitrofurantoin, first-generation cephalosporin, and third-generation cephalosporin for the 2012-2016 data. Antimicrobial choice algorithms were created using 2012-2016 results and tested on 2017-2018 data. RESULTS: For afebrile outpatients presenting with complicated cystitis, overall prevalence of resistance for trimethoprim-sulfamethoxazole, ciprofloxacin, nitrofurantoin, first-generation cephalosporin, and third-generation cephalosporin was 25.6%, 19.5%, 19.1%, 15.0%, and 6.9%, respectively. Consistent predictive factors influencing resistance to all 5 antimicrobials were patient place of residence (ZIP code), status of host urinary tract (complicated vs uncomplicated), and prior resistance to the antimicrobial. Resulting treatment algorithm for complicated cystitis (whether or not prior microbiologic data was available) outperformed real-life provider choice and our previously published algorithm for uncomplicated cystitis. CONCLUSION: Treatment algorithms for urinary tract infections are dependent on patient place of residence (ZIP code), status of the host urinary tract (complicated or uncomplicated), and prior urine culture resistance data. When using our complicated cystitis treatment algorithm regardless of uropathogen, our results outperformed real-life scenario provider choice and our prior published algorithm for uncomplicated cystitis, which can help guide empiric antimicrobial choice.

Surgical versus Medical Castration for Metastatic Prostate Cancer: Use and Overall Survival in a National Cohort.

PURPOSE: Surgical castration for metastatic prostate cancer is used less frequently than medical castration yet costs less, requires less followup and may be associated with fewer adverse effects. We evaluated temporal trends and factors associated with the use of surgical castration. MATERIALS AND METHODS: This retrospective cohort study sampled 24,805 men with newly diagnosed (de novo) metastatic prostate cancer from a national cancer registry in the United States (2004 to 2016). Multivariable logistic regression assessed the association between sociodemographic factors and surgery. Multivariable Cox regression evaluated the association between castration type and overall survival. RESULTS: Overall 5.4% of men underwent surgical castration. This figure decreased from 8.5% in 2004 to 3.5% in 2016 (per year later OR 0.89, 95% CI 0.87-0.91, p <0.001). Compared to Medicare, private insurance was associated with less surgery (OR 0.73, 95% CI 0.61-0.87, p <0.001) while Medicaid or no insurance was associated with more surgery (OR 1.68, 95% CI 1.34-2.11, p <0.001 and OR 2.12, 95% CI 1.58-2.85, p <0.001, respectively). Regional median income greater than $63,000 was associated with less surgery (vs income less than $38,000 OR 0.61, 95% CI 0.43-0.85, p=0.004). After a median followup of 30 months castration type was not associated with differences in survival (surgical vs medical HR 1.02, 95% CI 0.95-1.09, p=0.6). CONCLUSIONS: In a contemporary, real-world cohort surgical castration use is low and decreasing despite its potential advantages and similar survival rate compared to medical castration. Men with potentially limited health care access undergo more surgery, perhaps reflecting a provider bias toward the perceived benefit of permanent castration.

Morbidity of urologic surgical procedures: an analysis of rates, risk factors, and outcomes.

OBJECTIVE: To quantify national complication rates, perioperative outcomes, and predictors for a broad range of urologic procedures to demonstrate background rates and discuss benchmarking. METHODS: Urologic procedures from the National Surgical Quality Improvement Program (2006-2011) were analyzed to identify 30-day rates of 21 complications; outcomes (length of stay, reoperation, and death); and predictors including resident involvement for 18 specific procedures. Multivariate logistic regression models assessed predictors for any complication and for Clavien grade IV or V complication. RESULTS: A total of 39,700 procedures were included with abdominopelvic operations more morbid than endoscopic, scrotal, incontinence, or prolapse procedures. Cystectomy had the highest morbidity (10.8 days length of stay and 3.2% mortality), with 56% experiencing any complication followed by nephrectomy (21%), retroperitoneal lymph node dissection (20%), and radical retropubic prostatectomy (19%). Transurethral resection of bladder tumor (11%) and transurethral resection of the prostate (10%) had the highest rates for endoscopic procedures. Older age, American Society of Anesthesiologists class, dependent functional status, acute kidney injury (odds ratio [OR], 2.70 [1.89-3.87]), and ≥5 units preoperative transfusion (OR, 4.44 [3.40-5.80]) were the strongest predictors of any complication. Higher ORs of similar predictors along with chronic obstructive pulmonary disorder (OR, 1.52 [1.21-1.92]) and steroid use (OR, 1.51 [1.07-2.14]) were associated with Clavien grade IV or V complication. Resident involvement increased odds of any complication (OR, 1.18 [1.09-1.29]), mostly for abdominopelvic and urogynecologic procedures, but not Clavien grade IV or V complication (P = .55). CONCLUSION: Complication rates of urologic procedures based on the retrospective experience of few surgeons do not allow for appropriate benchmarking. Baseline rates and benchmarks derived from the National Surgical Quality Improvement Program may help hospitals better track deficient areas and improvements in quality of care. Many predictors were similar across procedures, although magnitudes differed, and resident trainees did not impact rates of serious complications (Clavien-Dindo grade IV or V).

Fluoroquinolone resistance in the rectal carriage of men in an active surveillance cohort: longitudinal analysis.

PURPOSE: Rectal swabs can identify men with fluoroquinolone resistant bacteria and decrease the infection rate after transrectal ultrasound guided prostate biopsy by targeted antimicrobial prophylaxis. We evaluated the rate of fluoroquinolone resistance in an active surveillance cohort with attention to factors associated with resistance and changes in resistance with time. MATERIALS AND METHODS: We evaluated 416 men with prostate cancer on active surveillance who underwent rectal swabs to assess the rate of fluoroquinolone resistance compared to that in men undergoing diagnostic transrectal ultrasound guided prostate biopsy. The chi-square test and Student t-test were used to compare categorical and continuous variables, respectively. Poisson regression analysis was used for multivariate analysis. RESULTS: On the initial swab fluoroquinolone resistance was found in 95 of 416 men (22.8%) on active surveillance compared to 54 of 221 (24.4%) in the diagnostic biopsy cohort (p = 0.675). Diabetes was found in 4.0% of the fluoroquinolone sensitive group vs 14.7% of the resistant group (p <0.001). Biopsy history was not associated with resistance. Of those with a resistant first swab 62.9% had a resistant second swab and 88.9% of those with 2 resistant swabs showed resistance on the third swab. Of men with a sensitive first swab 10.6% showed resistance on the second swab and 10.6% of those with 2 sensitive swabs had resistant third swabs. CONCLUSIONS: One of 4 men who present for surveillance and diagnostic transrectal ultrasound guided prostate biopsy have rectal flora resistant to fluoroquinolone. Resistance is significantly associated with diabetes but the number of prior biopsies is not. Men with fluoroquinolone resistant flora tend to remain resistant with time.

Establishment of a new prostate cancer multidisciplinary clinic: Format and initial experience.

BACKGROUND: The use of multidisciplinary clinics (MDCs) for outpatient cancer evaluation is increasing. MDCs may vary in format, and data on whether MDCs change prostate cancer (PCa) care are limited. Here we report on the setup and design of a relatively new PCa MDC clinic. Because MDC evaluation was associated with a comprehensive re-evaluation of all patients' staging and risk stratification data, we studied the frequency of changes in PCa grade and stage upon MDC evaluation, which provides a unique estimate of the magnitude of pathology, radiology, and exam-based risk stratification in a modern tertiary setting. METHODS: In 2008-2012, 887 patients underwent consultation for newly diagnosed PCa at the Johns Hopkins Hospital (JHH) weekly MDC. In a same-day process, patients are interviewed and examined in a morning clinic. Examination findings, radiology studies, and biopsy slides are then reviewed during a noon conference that involves real-time collaboration among JHH attending specialty physicians: urologists, radiation oncologists, medical oncologists, pathologists, and radiologists. During afternoon consultations, attending physicians appropriate to each patient's eligible treatment options individually meet with patients to discuss management strategies and/or clinical trials. Retrospective chart review identified presenting tumor characteristics based on outside assessment, which was compared with stage and grade as determined at MDC evaluation. RESULTS: Overall, 186/647 (28.7%) had a change in their risk category or stage. For example, 2.9% of men were down-classified as very-low-risk, rendering them eligible for active surveillance. 5.7% of men thought to have localized cancer were up-classified as metastatic, thus prompting systemic management approaches. Using NCCN guidelines as a benchmark, many men were found to have undergone non-indicated imaging (bone scan 23.9%, CT/MRI 47.4%). The three most chosen treatments after MDC evaluation were external beam radiotherapy ± androgen deprivation (39.3%), radical prostatectomy (32.0%), and active surveillance/expectant management (12.9%). CONCLUSIONS: A once-weekly same-day evaluation that involves simultaneous data evaluation, management discussion, and patient consultations from a multidisciplinary team of PCa specialists is feasible. Comprehensive evaluation at a tertiary referral center, as demonstrated in a modern MDC setting, is associated with critical changes in presenting disease classification in over one in four men.

Trends in renal surgery: robotic technology is associated with increased use of partial nephrectomy.

PURPOSE: Underuse of partial vs radical nephrectomy for renal tumors was noted in recent population based analyses. An explanation is the learning curve associated with laparoscopic partial nephrectomy. We analyzed state trends in renal surgery and their relationship to the introduction of robotic technology. MATERIALS AND METHODS: We used the Maryland HSCRC (Health Services Cost Review Commission) database to identify patients who underwent radical or partial nephrectomy, or renal ablation from 2000 to 2011. Utilization trends, and associated patient and hospital factors were analyzed using multivariate logistic regression. ICD-9 robotic modifier codes were established in October 2008. RESULTS: Of the 14,260 patients included in analysis 11,271 (79.0%), 2,622 (18.4%) and 367 (2.6%) underwent radical and partial nephrectomy, and renal ablation, respectively. Partial nephrectomy increased from 8.6% in 2000 to 27% in 2011. Open radical nephrectomy decreased by 33%, while minimally invasive radical nephrectomy increased by 15%. Robot-assisted laparoscopic partial nephrectomy increased from 2008 to 2011, attaining a 14% rate at university and 10% at nonuniversity hospitals (p = 0.03). It was associated with increased partial nephrectomy (OR 9.67, p <0.001). Younger age, male gender and low patient complexity predicted partial nephrectomy on overall analysis, while higher hospital volume and university status were predictors only in earlier years. CONCLUSIONS: Partial nephrectomy use increased in Maryland from 2001 to 2011, which was facilitated by robotic technology. Associations with hospital factors decreased with time. These data suggest that robotic technology may enable surgeons across practice settings to more frequently perform nephron sparing surgery.

Towards prevention of acute lung injury: frequency and outcomes of emergency department patients at-risk - a multicenter cohort study.

BACKGROUND: Few emergency department (ED) evaluations on acute lung injury (ALI) have been carried out; hence, we sought to describe a cohort of hospitalized ED patients at risk for ALI development. METHODS: Patients presenting to the ED with at least one predisposing condition to ALI were included in this study, a subgroup analysis of a multicenter observational cohort study (USCIITG-LIPS 1). Patients who met ALI criteria within 6 h of initial ED assessment, received end-of-life care, or were readmitted during the study period were excluded. Primary outcome was frequency of ALI development; secondary outcomes were ICU and hospital mortality. RESULTS: Twenty-two hospitals enrolled 4,361 patients who were followed from the ED to hospital discharge. ALI developed in 303 (7.0 %) patients at a median onset of 2 days (IQR 2-5). Of the predisposing conditions, frequency of ALI development was highest in patients who had aortic surgery (43 %) and lowest in patients with pancreatitis (2.8 %). Compared to patients who did not develop ALI, those who did had higher ICU (24 % vs. 3.0 %, p < 0.001) and hospital (28 % vs. 4.6 %, p < 0.001) mortality, and longer hospital length of stay (16 vs. 5 days, p < 0.001). Among the 22 study sites, frequency of ALI development varied from less than 1 % to more than 12 % after adjustment for APACHE II. CONCLUSIONS: Seven percent of hospitalized ED patients with at least one predisposing condition developed ALI. The frequency of ALI development varied significantly according to predisposing conditions and across institutions. Further research is warranted to determine the factors contributing to ALI development.