Race-insurance disparities in prostate patients' magnetic resonance imaging biopsies and their subsequent cancer care: a New York State cohort study.

For organ-confined prostate cancer, socioeconomic factors influencing Magnetic Resonance Imaging (MRI)-guided biopsy utilization and downstream prostate cancer patients' care are unknown. This retrospective, observational cohort study used the New York Statewide Planning and Research Cooperative System (SPARCS) billing-code driven database to examine the impact of prostate patients' socioeconomic characteristics on prostate cancer care defined as initial biopsy, 2-month post-biopsy cancer diagnoses, and within 1-year cancer-related intervention, controlling for other risk factors. From 2011-2017, the population studied (n = 18,253) included all New York State-based, male, residents aged 18 to 75 without a prior prostatectomy receiving a first-time biopsy; 760 such patient records in 2016 were removed due to data quality concerns. Major exposures included patient age, race, ethnicity and insurance. The major outcome included receipt of MRI biopsy versus standard biopsy and for these sub-populations, subsequent 2-month post-biopsy metastatic versus non-metastatic prostate cancer diagnosis and within 1-year prostate cancer treatment (prostatectomy with or without radiation versus prostatectomy-only) were compared using dichotomous (primary) and time-to-event (secondary) endpoints. Of 17,493 patients with a first-time prostate biopsy, 3.89% had MRI guided biopsies; of the 17,128 patients with no pre-biopsy cancer diagnosis, the subsequent prostate cancer diagnosis rate was 42.59%. For 6,754 non-metastatic prostate cancer patients with 1-year follow-up, 1,674 (24.79%) received surgery (with or without radiation) and 495 (7.33%) received radiation-only. Holding other factors constant, multivariable regression models identified that race-insurance was a primary predictor of MRI-guided biopsy use. Compared to commercially insured White patients, Black patients across all insurance categories received MRI-guided biopsies less frequently; Commercially insured and self-pay Black patients also had increased chance of prostate cancer diagnosis. Across all insurers, Black patients had lower likelihood of prostatectomies. In contrast, Black and White patients with government insurance were more likely to have within 1-year radiation-only treatments versus commercially insured White patients. Thus, across the prostate cancer care continuum, race-insurance affected prostate cancer-related service utilization. Future research should evaluate the generalizability of these New York State findings.

Keratin 17 is a sensitive and specific biomarker of urothelial neoplasia.

There is a clinical need to identify novel biomarkers to improve diagnostic accuracy for the detection of urothelial tumors. The current study aimed to evaluate keratin 17 (K17), an oncoprotein that drives cell cycle progression in cancers of multiple anatomic sites, as a diagnostic biomarker of urothelial neoplasia in bladder biopsies and in urine cytology specimens. We evaluated K17 expression by immunohistochemistry in formalin-fixed, paraffin embedded tissue specimens of non-papillary invasive urothelial carcinoma (UC) (classical histological cases), high grade papillary UC (PUC-LG), low grade papillary UC (PUC-HG), papillary urothelial neoplasia of low malignant potential (PUNLMP), and normal bladder mucosa. A threshold was established to dichotomize K17 status in tissue specimens as positive vs. negative, based on the proportion of cells that showed strong staining. In addition, K17 immunocytochemistry was performed on urine cytology slides, scoring positive test results based on the detection of K17 in any urothelial cells. Mann-Whitney and receiver operating characteristic analyses were used to compare K17 expression between histologic diagnostic categories. The median proportion of K17 positive tumor cells was 70% (range 20-90%) in PUNLMP, 30% (range 5-100%) in PUC-LG, 20% (range 1-100%), in PUC-HG, 35% (range 5-100%) in UC but staining was rarely detected (range 0-10%) in normal urothelial mucosa. Defining cases in which K17 was detected in ≥10% of cells were considered positive, the sensitivity of K17 in biopsies was 89% (95% CI: 80-96%) and the specificity was 88% (95% CI: 70-95%) to distinguish malignant lesions (PUC-LG, PUC-HG, and UC) from normal urothelial mucosa. Furthermore, K17 immunocytochemistry had a sensitivity of 100% and a specificity of 96% for urothelial carcinoma in 112 selected urine specimens. Thus, K17 is a sensitive and specific biomarker of urothelial neoplasia in tissue specimens and should be further explored as a novel biomarker for the cytologic diagnosis of urine specimens.

Does increasing the nodal yield improve outcomes in patients without nodal metastasis at radical cystectomy?

PURPOSE: To determine whether the number of lymph nodes (LNs) examined is associated with outcomes in patients without nodal metastasis after radical cystectomy (RC). PATIENTS AND METHODS: We retrospectively analyzed data from 4,188 patients treated at 12 centers with RC and pelvic lymphadenectomy without neo-adjuvant chemotherapy for urothelial carcinoma of the bladder (UCB). Outcomes of patients without LN metastasis (n = 3,088) were examined according to the LN yield analyzed as continuous variable, tertiles, and using the cutoffs of ≥ 9 and ≥ 20. RESULTS: The median nodal yield was 18 (range 1-123; IQR:20). A total of 2591 (84 %) and 1445 (47 %) patients had a LN yield ≥ 9 and ≥ 20, respectively. Median follow-up was 47 months (IQR:70). In multivariable analyses that adjusted for the standard clinicopathologic factors, higher LN yield was associated with a decreased risk of disease recurrence (continuous: HR = 0.996, p = 0.05; 3rd vs 1st tertile: HR = 0.853, p = 0.048; cutoff ≥ 20: HR = 0.851, p = 0.032). In the subgroups of patients with muscle-invasive UCB or those with ≥ 9 LN removed, LN yield was not associated with outcomes (p values >0.05). CONCLUSIONS: In this large multicenter cohort of patients with node-negative UCB, higher nodal yield improved recurrence-free survival when all patients were analyzed. Patients with a high LN yield (≥ 20 LN removed or 3rd tertile) had the largest benefit. The lack of prognostic significance of LN yield in patients with muscle-invasive UCB or those stratified by 9 LNs removed suggests that this effect is weak. Further prospective studies are needed to help identify preoperatively the optimal template for each patient.

Nox4 mediates renal cell carcinoma cell invasion through hypoxia-induced interleukin 6- and 8- production.

BACKGROUND: Inflammatory cytokines are detected in the plasma of patients with renal cell carcinoma (RCC) and are associated with poor prognosis. However, the primary cell type involved in producing inflammatory cytokines and the biological significance in RCC remain unknown. Inflammation is associated with oxidative stress, upregulation of hypoxia inducible factor 1-alpha, and production of pro-inflammatory gene products. Solid tumors are often heterogeneous in oxygen tension together suggesting that hypoxia may play a role in inflammatory processes in RCC. Epithelial cells have been implicated in cytokine release, although the stimuli to release and molecular mechanisms by which they are released remain unclear. AMP-activated protein kinase (AMPK) is a highly conserved sensor of cellular energy status and a role for AMPK in the regulation of cell inflammatory processes has recently been demonstrated. METHODS AND PRINCIPAL FINDINGS: We have identified for the first time that interleukin-6 and interleukin-8 (IL-6 and IL-8) are secreted solely from RCC cells exposed to hypoxia. Furthermore, we demonstrate that the NADPH oxidase isoform, Nox4, play a key role in hypoxia-induced IL-6 and IL-8 production in RCC. Finally, we have characterized that enhanced levels of IL-6 and IL-8 result in RCC cell invasion and that activation of AMPK reduces Nox4 expression, IL-6 and IL-8 production, and RCC cell invasion. CONCLUSIONS/SIGNIFICANCE: Together, our data identify novel mechanisms by which AMPK and Nox4 may be linked to inflammation-induced RCC metastasis and that pharmacological activation of AMPK and/or antioxidants targeting Nox4 may represent a relevant therapeutic intervention to reduce IL-6- and IL-8-induced inflammation and cell invasion in RCC.

Management of post-chemotherapy residual mass in patients with metastatic nonseminomatous germ cell tumors of the testis.

The basis of treatment for advanced germ cell tumors is chemotherapy and surgical resection of residual disease. Surgery has maintained its role in staging and therapeutic management. Despite these advances, much of the outcomes depend on proper patient selection. Complete removal of all post-chemotherapy residual masses remains the standard of care in the treatment of advanced nonseminomatous germ cell tumors both within and outside of the retroperitoneum.

Atorvastatin ameliorates tubulointerstitial fibrosis and protects renal function in chronic partial ureteral obstruction cases.

PURPOSE: Tubulointerstitial fibrosis, the histological feature of chronic obstructive nephropathy, is delineated in complete unilateral ureteral obstruction models. Histological changes during chronic partial ureteral obstruction are not well studied. We describe changes in a rat model of partial ureteral obstruction. We examined the effects of atorvastatin on histological alterations, fibrosis and function in this model. MATERIALS AND METHODS: All rats underwent right nephrectomy. To create partial ureteral obstruction the left ureter was incorporated into the psoas muscle, which was split and reapproximated. Excretory urogram, histology, Western blot of alpha-smooth muscle actin and renal clearance were examined in rats with sham, 14-day or 30-day partial ureteral obstruction. Obstructed rats received a regular or a diet supplemented with 50 mg/kg body weight atorvastatin per day. RESULTS: At 14 days of partial ureteral obstruction pyelogram showed hydronephrosis, which was more pronounced on obstruction day 30. Histological studies on obstruction days 14 and 30 revealed tubulointerstitial fibrosis in the medulla and cortex. Atorvastatin significantly decreased tubulointerstitial fibrosis seen in alpha-smooth muscle actin expression. On obstruction day 14 or 30 the glomerular filtration rate in rats on a regular diet was significantly lower than in sham PUO rats or rats on atorvastatin. CONCLUSIONS: This model of partial ureteral obstruction enables chronic studies of morphological and histological changes of the obstructed kidney. It showed progressive fibrosis and decreased filtration function. Atorvastatin ameliorated fibrosis and helped preserve kidney filtration function.

Understanding attitudes towards use of medication in substance abuse treatment: A multilevel approach.

Individual and organizational variables influence attitudes towards use of naltrexone, methadone, and buprenorphine for the treatment of alcohol and drug disorders. Prior research has not considered both sets of influences simultaneously. Hierarchical linear modeling tested the contribution of individual and organizational variables using data from the National Drug Abuse Treatment Clinical Trials Network treatment unit and workforce surveys (n = 2,269 staff nested within 247 treatment units). Individual-level variables consistently had more influence on attitudes, but a unique blend of variables existed for each medication. One predictor, support for psychiatric medications, influenced attitudes across all medications. Staff attitudes towards addiction medications varied significantly between treatment units. Implications for increasing the appropriate use of addiction medications are discussed.