Prognostic capabilities and clinical utility of cell cycle progression testing, prostate imaging reporting and data system, version 2, and clinicopathologic data in management of localized prostate cancer.

OBJECTIVES: To compare the prognostic capabilities and clinical utility of the cell cycle progression (CCP) gene expression classifier test, multiparametric magnetic resonance imaging (mpMRI) with Prostate Imaging Reporting and Data System (PI-RADS) scoring, and clinicopathologic data in select prostate cancer (PCa) medical management scenarios. PATIENTS AND METHODS: Retrospective, observational analysis of patients (N = 222) ascertained sequentially from a single urology practice from January 2015 to June 2018. Men were included if they had localized PCa, a CCP score, and an mpMRI PI-RADS v2 score. Cohort 1 (n = 156): men with newly diagnosed PCa, with or without a previous negative biopsy. Cohort 2 (n = 66): men who initiated active surveillance (AS) without CCP testing, but who received the test during AS. CCP was combined with the UCSF Cancer of the Prostate Risk Assessment (CAPRA) score to produce a clinical cell-cycle risk (CCR) score, which was reported in the context of a validated AS threshold. Spearman's rank correlation test was used to evaluate correlations between variables. Generalized linear models were used to predict binary Gleason score category and medical management selection (AS or curative therapy). Likelihood-ratio tests were used to determine predictor significance in both univariable and multivariable models. RESULTS: In the combined cohorts, modest but significant correlations were observed between PI-RADS score and CCP (rs = 0.22, P = 8.1 × 10-4), CAPRA (rs= 0.36, P = 4.8 × 10-8), or CCR (rs = 0.37, P = 2.0 × 10-8), suggesting that much of the prognostic information captured by these measures is independent. When accounting for CAPRA and PI-RADS score, CCP was a significant predictor of higher-grade tumor after radical prostatectomy, with the resected tumor approximately 4 times more likely to harbor Gleason ≥4+3 per 1-unit increase in CCP in Cohort 1 (Odds Ratio [OR], 4.10 [95% confidence interval [CI], 1.46, 14.12], P = 0.006) and in the combined cohorts (OR, 3.72 [95% CI, 1.39, 11.88], P = 0.008). On multivariable analysis, PI-RADS score was not a significant predictor of post-radical prostatectomy Gleason score. Both CCP and CCR were significant and independent predictors of AS versus curative therapy in Cohort 1 on multivariable analysis, with each 1-unit increase in score corresponding to an approximately 2-fold greater likelihood of selecting curative therapy (CCP OR, 2.08 [95% CI, 1.16, 3.94], P = 0.014) (CCR OR, 2.33 [95% CI, 1.48, 3.87], P = 1.5 × 10-4). CCR at or below the AS threshold significantly reduced the probability of selecting curative therapy over AS (OR, 0.28 [95% CI, 0.13, 0.57], P = 4.4 × 10-4), further validating the clinical utility of the AS threshold. CONCLUSION: CCP was a better predictor of both tumor grade and subsequent patient management than was PI-RADS. Even in the context of targeted biopsy, molecular information remains essential to ensure precise risk assessment for men with newly diagnosed PCa.

Effects of aging on glomerular function and number in living kidney donors.

To elucidate the pathophysiologic changes in the kidney due to aging, we used physiological, morphometric, and imaging techniques to quantify GFR and its determinants in a group of 24 older (≥ 55 years) compared to 33 younger (≤ 45 years) living donors. Mathematical modeling was used to estimate the glomerular filtration coefficients for the whole kidney (K(f)) and for single nephrons (SNK(f)), as well as the number of filtering glomeruli (N(FG)). Compared to younger donors, older donors had a modest (15%) but significant depression of pre-donation GFR. Mean whole-kidney K(f), renocortical volume, and derived N(FG) were also significantly decreased in older donors. In contrast, glomerular structure and SNK(f) were not different in older and younger donors. Derived N(FG) in the bottom quartile of older donors was less than 27% of median-derived N(FG) in the two kidneys of younger donors. Nevertheless, the remaining kidney of older donors exhibited adaptive hyperfiltration and renocortical hypertrophy post-donation, comparable to that of younger donors. Thus, our study found the decline of GFR in older donors is due to a reduction in K(f) attributable to glomerulopenia. We recommend careful monitoring for and control of post-donation comorbidities that could exacerbate glomerular loss.

The dangling diaphragm sign: sensitivity and comparison with existing CT signs of blunt traumatic diaphragmatic rupture.

The objectives of our study were to describe a new CT sign of diaphragmatic injury, the "dangling diaphragm" sign, and assess its comparative utility relative to other signs in the diagnosis of diaphragmatic injury resulting from blunt trauma. CT scans of 16 blunt trauma patients (12 men and four women, mean age 36.6 years old) with surgically proven diaphragmatic injury and 32 blunt trauma patients (24 men and eight women; mean age 37.4 years old) without evidence of diaphragmatic injury at surgery were blindly reviewed by three board certified radiologists specializing in body imaging. Studies were evaluated for the presence of established signs of diaphragmatic injury, as well as the dangling diaphragm sign, in which the free edge of the torn hemidiaphragm curls inward from its normal course parallel to the body wall. The sensitivity and specificity of each sign were determined, as were the correlation between the signs and the interobserver agreement in evaluation of these findings. The radiologists' overall impression as to whether rupture was present was also recorded. In select cases, coronal and/or sagittal reformatted images were available, and they were reviewed following evaluation of the original axial images. Any change in interpretation due to these images was noted. The sensitivity of the radiologists' overall impression for detection of diaphragmatic injury was 77%, with 98% specificity. Individual signs of diaphragmatic injury had sensitivities ranging from 44% to 69%, with specificities of 98% to 100%. The dangling diaphragm sign had a sensitivity of 54% and a specificity of 98%, similar to the other signs. Multiple signs were present in most cases of diaphragmatic injury, and coronal and sagittal reformatted images had little impact. Diaphragmatic injury remains a challenging radiographic diagnosis. The dangling diaphragm is a conspicuous sign of diaphragmatic injury, and awareness of it may increase detection of diaphragmatic injury on CT studies.

An evaluation of multidetector computed tomography in detecting pancreatic injury: results of a multicenter AAST study.

BACKGROUND: Efforts to determine the suitability of low-grade pancreatic injuries for nonoperative management have been hindered by the inaccuracy of older computed tomography (CT) technology for detecting pancreatic injury (PI). This retrospective, multicenter American Association for the Surgery of Trauma-sponsored trial examined the sensitivity of newer 16- and 64-multidetector CT (MDCT) for detecting PI, and sensitivity/specificity for the identification of pancreatic ductal injury (PDI). METHODS: Patients who received a preoperative 16- or 64-MDCT followed by laparotomy with a documented PI were enrolled. Preoperative MDCT scans were classified as indicating the presence (+) or absence (-) of PI and PDI. Operative notes were reviewed and all patients were confirmed as PI (+), and then classified as PDI (+) or (-). As all patients had PI, an analysis of PI specificity was not possible. PI patients formed the pool for further PDI analysis. As sensitivity and specificity data were available for PDI, multivariate logistic regression was performed for PDI patients using the presence or absence of agreement between CT and operative note findings as an independent variable. Covariates were age, gender, Injury Severity Score, mechanism of injury, presence of oral contrast, presence of other abdominal injuries, performance of the scan as part of a dedicated pancreas protocol, and image thickness < or =3 mm or > or =5 mm. RESULTS: Twenty centers enrolled 206 PI patients, including 71 PDI (+) patients. Intravenous contrast was used in 203 studies; 69 studies used presence of oral contrast. Eight-nine percent were blunt mechanisms, and 96% were able to have their duct status operatively classified as PDI (+) or (-). The sensitivity of 16-MDCT for all PI was 60.1%, whereas 64-MDCT was 47.2%. For PDI, the sensitivities of 16- and 64-MDCT were 54.0% and 52.4%, respectively, with specificities of 94.8% for 16-MDCT scanners and 90.3% for 64-MDCT scanners. Logistic regression showed that no covariates were associated with an increased likelihood of detecting PDI for either 16- or 64-MDCT scanners. The area under the curve was 0.66 for the 16-MDCT PDI analysis and 0.77 for the 64-MDCT PDI analysis. CONCLUSION: Sixteen and 64-MDCT have low sensitivity for detecting PI and PDI, while exhibiting a high specificity for PDI. Their use as decision-making tools for the nonoperative management of PI are, therefore, limited.