Chaochen You

Variation in the intensity of hematuria evaluation: a target for primary care quality improvement

BACKGROUND Hematuria is a common clinical finding and represents the most frequent presenting sign of bladder cancer. The American Urological Association recommends cystoscopy and abdomino-pelvic imaging for patients aged more than 35 years. Nonetheless, less than half of patients presenting with hematuria undergo proper evaluation. We sought to identify clinical and nonclinical factors associated with evaluation of persons with newly diagnosed hematuria. METHODS We performed a retrospective cohort study, using claims data and laboratory values. The primary exposure was practice site, as a surrogate for nonclinical, potentially modifiable sources of variation. Primary outcomes were cystoscopy or abdomino-pelvic imaging within 180 days after hematuria diagnosis. We modeled the association between clinical and nonclinical factors and appropriate hematuria evaluation. RESULTS We identified 2455 primary care patients aged 40 years or more and diagnosed with hematuria between 2004 and 2012 in the absence of other explanatory diagnosis; 13.7% of patients underwent cystoscopy within 180 days. Multivariate logistic regression revealed significant variation between those who did and did not undergo evaluation in age, gender, and anticoagulant use (P < .001, P = .036, P = .028, respectively). Addition of practice site improved the predictive discrimination of each model (P < .001). Evaluation was associated with a higher rates of genitourinary neoplasia diagnosis. CONCLUSIONS Patients with hematuria rarely underwent complete evaluation. Although established risk factors for malignancy were associated with increasing use of diagnostic testing, factors unassociated with risk, such as practice site, also accounted for significant variation. Inconsistency across practice sites is undesirable and may be amenable to quality improvement interventions.

Racial variation in the quality of surgical care for bladder cancer

Differences in quality of care may contribute to racial variation in outcomes of bladder cancer (BCa). Quality indicators in patients undergoing surgery for BCa include the use of high‐volume surgeons and high‐volume hospitals, and, when clinically indicated, receipt of pelvic lymphadenectomy, receipt of continent urinary diversion, and undergoing radical cystectomy instead of partial cystectomy. The authors compared these quality indicators as well as adverse perioperative outcomes in black patients and white patients with BCa.

Incidence and predictors of understaging in patients with clinical T1 urothelial carcinoma undergoing radical cystectomy

To evaluate predictors of understaging in patients with presumed non‐muscle‐invasive bladder cancer (NMIBC) identified on transurethral resection of bladder tumour (TURBT) who underwent radical cystectomy (RC) with attention to the role of a restaging TURBT.

Loss of FOXA1 Drives Sexually Dimorphic Changes in Urothelial Differentiation and Is an Independent Predictor of Poor Prognosis in Bladder Cancer.

We previously found loss of forkhead box A1 (FOXA1) expression to be associated with aggressive urothelial carcinoma of the bladder, as well as increased tumor proliferation and invasion. These initial findings were substantiated by The Cancer Genome Atlas, which identified FOXA1 mutations in a subset of bladder cancers. However, the prognostic significance of FOXA1 inactivation and the effect of FOXA1 loss on urothelial differentiation remain unknown. Application of a univariate analysis (log-rank) and a multivariate Cox proportional hazards regression model revealed that loss of FOXA1 expression is an independent predictor of decreased overall survival. An ubiquitin Cre-driven system ablating Foxa1 expression in urothelium of adult mice resulted in sex-specific histologic alterations, with male mice developing urothelial hyperplasia and female mice developing keratinizing squamous metaplasia. Microarray analysis confirmed these findings and revealed a significant increase in cytokeratin 14 expression in the urothelium of the female Foxa1 knockout mouse and an increase in the expression of a number of genes normally associated with keratinocyte differentiation. IHC confirmed increased cytokeratin 14 expression in female bladders and additionally revealed enrichment of cytokeratin 14-positive basal cells in the hyperplastic urothelial mucosa in male Foxa1 knockout mice. Analysis of human tumor specimens confirmed a significant relationship between loss of FOXA1 and increased cytokeratin 14 expression.

SOX2 expression in the developing, adult, as well as, diseased prostate.

Background:SOX2 is a member of SOX (SRY-related high mobility group box) family of transcription factors.Methods:In this study, we examined the expression of SOX2 in murine and human prostatic specimens by immunohistochemistry.Results:We found that SOX2 was expressed in murine prostates during budding morphogenesis and in neuroendocrine (NE) prostate cancer (PCa) murine models. Expression of SOX2 was also examined in human prostatic tissue. We found that SOX2 was expressed in 26 of the 30 BPH specimens. In these BPH samples, expression of SOX2 was limited to basal epithelial cells. In contrast, 24 of the 25 primary PCa specimens were negative for SOX2. The only positive primary PCa was the prostatic NE tumor, which also showed co-expression of synaptophysin. Additionally, the expression of SOX2 was detected in all prostatic NE tumor xenograft lines. Furthermore, we have examined the expression of SOX2 on a set of tissue microarrays consisting of metastatic PCa tissues. Expression of SOX2 was detected in at least one metastatic site in 15 of the 24 patients with metastatic castration-resistant PCa; and the expression of SOX2 was correlated with synaptophysin.Conclusions:SOX2 was expressed in developing prostates, basal cells of BPH, as well as prostatic NE tumors.

Variation in the Diagnostic Evaluation among Persons with Hematuria: Influence of Gender, Race and Risk Factors for Bladder Cancer

Purpose: We sought to determine whether race, gender and number of bladder cancer risk factors are significant predictors of hematuria evaluation. Materials and Methods: We used self‐reported data from SCCS (Southern Community Cohort Study) linked to Medicare claims data. Evaluation of subjects diagnosed with incident hematuria was considered complete if imaging and cystoscopy were performed within 180 days of diagnosis. Exposures of interest were race, gender and risk factors for bladder cancer. Results: Of the 1,412 patients evaluation was complete in 261 (18%). On our adjusted analyses African American patients were less likely than Caucasian patients to undergo any aspect of evaluation, including urology referral (OR 0.72, 95% CI 0.56–0.93), cystoscopy (OR 0.67, 95% CI 0.50–0.89) and imaging (OR 0.75, 95% CI 0.59–0.95). Women were less likely than men to be referred to a urologist (OR 0.59, 95% CI 0.46–0.76). Also, although all patients with 2 or 3 risk factors had 31% higher odds of urology referral (OR 1.31, 95% CI 1.02–1.69), adjusted analyses indicated that this effect was only apparent among men. Conclusions: Only 18% of patients with an incident hematuria diagnosis underwent complete hematuria evaluation. Gender had a substantial effect on referral to urology when controlling for socioeconomic factors but otherwise it had an unclear role on the quality of evaluation. African American patients had markedly lower rates of thorough evaluation than Caucasian patients. Number of risk factors predicted referral to urology among men but it was otherwise a poor predictor of evaluation. There is opportunity for improvement by increasing the completion of hematuria evaluations, particularly in patients at high risk and those who are vulnerable.

Benchmarking the Use of a Rapid Response Team by Surgical Services at a Tertiary Care Hospital

BACKGROUND Rapid response teams (RRT) are used to prevent adverse events in patients with acute clinical deterioration, and to save costs of unnecessary transfer in patients with lower-acuity problems. However, determining the optimal use of RRT services is challenging. One method of benchmarking performance is to determine whether a departments event rate is commensurate with its volume and acuity. STUDY DESIGN Using admissions between 2009 and 2011 to 18 distinct surgical services at a tertiary care center, we developed logistic regression models to predict RRT activation, accounting for days at-risk for RRT and patient acuity, using claims modifiers for risk of mortality (ROM) and severity of illness (SOI). The model was used to compute observed-to-expected (O/E) RRT use by service. RESULTS Of 45,651 admissions, 728 (1.6%, or 3.2 per 1,000 inpatient days) resulted in 1 or more RRT activations. Use varied widely across services (0.4% to 6.2% of admissions; 1.39 to 8.73 per 1,000 inpatient days, unadjusted). In the multivariable model, the greatest contributors to the likelihood of RRT were days at risk, SOI, and ROM. The O/E RRT use ranged from 0.32 to 2.82 across services, with 8 services having an observed value that was significantly higher or lower than predicted by the model. CONCLUSIONS We developed a tool for identifying outlying use of an important institutional medical resource. The O/E computation provides a starting point for further investigation into the reasons for variability among services, and a benchmark for quality and process improvement efforts in patient safety.

Predictors of recurrence in patients with high-risk pathology after prostatectomy

Background: To determine the pattern of recurrence in patients with high-risk pathology at radical prostatectomy and to identify disease characteristics associated with clinical and biochemical recurrence (BCR). Methods: We identified 893 patients who underwent radical prostatectomy between January 2000 and June 2009 with pathologic T3N0 disease or T2N0 disease and positive surgical margins who did not receive adjuvant radiotherapy. We evaluated univariate relationships between individual covariates and risk of BCR. We then fit a multivariable Cox regression model to evaluate the independent predictive power of relevant covariates, and utilized the multivariate model to demonstrate the risk of BCR. Results: Of the 893 patients, 519 (58.1%) had pT3 disease while 374 (41.9%) had pT2 disease with positive surgical margins. Within the cohort, 26.0% sustained BCR during a median follow up of 55.0 months (IQR 39.5-78.8). Pre-operative PSA, Gleason score, extraprostatic extension and seminal vesicle invasion were independently associated with time to recurrence, while surgical margin status was not. Five-year BCR-free survival was 79% for pT2 margin+, 67% for pT3a and 54% for pT3b; 88% for Gleason 5-6, 69% for Gleason 7, and 51% for Gleason 8-10. Conclusions: BCR is common in patients with high-risk pathologic features, but many such patients exhibit long-term diseasefree survival. By using common clinicopathologic features, it is possible to risk stratify this heterogeneous group of patients to facilitate early radiotherapy for those at high-risk of recurrence while minimizing morbidity in those who stand to gain little from additional treatment.