Diagnostic value of MRI-based PSA density in predicting transperineal sector-guided prostate biopsy outcomes

PURPOSE: Prostate-specific antigen (PSA) density (PSAD) has potential to increase the diagnostic utility of PSA, yet has had poor uptake in clinical practice. We aimed to determine the diagnostic value of magnetic resonance imaging-derived PSAD (MR-PSAD) in predicting transperineal sector-guided prostate biopsy (TPSB) outcomes. MATERIALS AND METHODS: Men presenting for primary TPSB from 2007 to 2014 were considered. Histological outcomes were assessed and defined as: presence of any cancer or significant cancer defined as presence of Gleason 4 and/or maximum tumour core length (MCCL) ≥ 4 mm (G4); or Gleason 4 and/or MCCL ≥ 6 mm (G6). Sensitivity, specificity and positive and negative predictive values were calculated, and receiver operating characteristics (ROC) curves were generated to compare MR-PSAD and PSA. RESULTS: Six hundred fifty-nine men were evaluated with mean age 62.5 ± 9 years, median PSA 6.7 ng/ml (range 0.5-40.0), prostate volume 40 cc (range 7-187) and MR-PSAD 0.15 ng/ml/cc (range 0.019-1.3). ROC area under the curve (95% CI) was significantly better for MR-PSAD than PSA for all cancer definitions (p < 0.001): 0.73 (0.70-0.76) versus 0.61 (0.57-0.64) for any cancer; 0.75 (0.71-0.78) versus 0.66 (0.62-0.69) for G4; and 0.77 (0.74-0.80) versus 0.68 (0.64-0.71) for G6. Sensitivities for MR-PSAD < 0.1 ng/ml/cc were 85.0, 89.9 and 91.9% for any, G4 and G6 cancer, respectively. CONCLUSION: MR-PSAD may be better than total PSA in determining risk of positive biopsy outcome. Its use may improve risk stratification and reduce unnecessary biopsies

Pre-prostatectomy membranous urethral length as a predictive factor of post prostatectomy incontinence requiring surgical intervention with an artificial urinary sphincter or a male sling

AIMS: To ascertain whether the membranous urethral length (MUL) is predictive of postprostatectomy incontinence (PPI) that requires surgery such as artificial urinary sphincter (AUS) or male sling (MS). METHODS: Men who had undergone AUS or MS for PPI were identified from a prospectively maintained database and compared to a control group of men who were continent at 12 months after radical prostatectomy. MUL in sagittal and coronal planes, sphincter height and width were measured on prebiopsy T2‐weighted MRI scans. Sphincter volume was estimated as an ellipsoid cylinder. RESULTS: A total of 95 patients (64 AUS and 31 MS) were compared to 60 continent controls. There was no statistical difference in presenting PSA, prostate volume, and T‐stage. The mean MUL in sagittal and coronal planes was 11.31 mm (SD: 2.6, range: 6–17 mm) and 11.43 mm (SD: 2.94, range: 5–17 mm) in patients who had AUS and MS, respectively; 15.23 mm (SD: 4.2, range: 8.25–25 mm) and 15.75 mm (SD: 4.1, range: 8–24 mm) in controls (p 17 mm compared to 35% (20/57 sagittal, 20/58 coronal) of controls. The odds ratio for requiring surgery for PPI was 13.4 for sagittal MUL 17 mm are unlikely to require surgery for PPI whereas an MUL <12 mm significantly increases the risk of requiring surgery for PPI. MUL should be considered when discussing treatment options for prostate cancer

Diagnostic value of MRI-based PSA density in predicting transperineal sector-guided prostate biopsy outcomes

PURPOSE: Prostate-specific antigen (PSA) density (PSAD) has potential to increase the diagnostic utility of PSA, yet has had poor uptake in clinical practice. We aimed to determine the diagnostic value of magnetic resonance imaging-derived PSAD (MR-PSAD) in predicting transperineal sector-guided prostate biopsy (TPSB) outcomes. MATERIALS AND METHODS: Men presenting for primary TPSB from 2007 to 2014 were considered. Histological outcomes were assessed and defined as: presence of any cancer or significant cancer defined as presence of Gleason 4 and/or maximum tumour core length (MCCL) ≥ 4 mm (G4); or Gleason 4 and/or MCCL ≥ 6 mm (G6). Sensitivity, specificity and positive and negative predictive values were calculated, and receiver operating characteristics (ROC) curves were generated to compare MR-PSAD and PSA. RESULTS: Six hundred fifty-nine men were evaluated with mean age 62.5 ± 9 years, median PSA 6.7 ng/ml (range 0.5-40.0), prostate volume 40 cc (range 7-187) and MR-PSAD 0.15 ng/ml/cc (range 0.019-1.3). ROC area under the curve (95% CI) was significantly better for MR-PSAD than PSA for all cancer definitions (p < 0.001): 0.73 (0.70-0.76) versus 0.61 (0.57-0.64) for any cancer; 0.75 (0.71-0.78) versus 0.66 (0.62-0.69) for G4; and 0.77 (0.74-0.80) versus 0.68 (0.64-0.71) for G6. Sensitivities for MR-PSAD < 0.1 ng/ml/cc were 85.0, 89.9 and 91.9% for any, G4 and G6 cancer, respectively. CONCLUSION: MR-PSAD may be better than total PSA in determining risk of positive biopsy outcome. Its use may improve risk stratification and reduce unnecessary biopsies

IL-27 signaling is crucial for survival of mice infected with African trypanosomes via preventing lethal effects of CD4+ T cells and IFNγ

African trypanosomes are extracellular protozoan parasites causing a chronic debilitating disease associated with a persistent inflammatory response. Maintaining the balance of the inflammatory response via downregulation of activation of M1-type myeloid cells was previously shown to be crucial to allow prolonged survival. Here we demonstrate that infection with African trypanosomes of IL-27 receptor-deficient (IL-27R(-/-)) mice results in severe liver immunopathology and dramatically reduced survival as compared to wild-type mice. This coincides with the development of an exacerbated Th1-mediated immune response with overactivation of CD4(+) T cells and strongly enhanced production of inflammatory cytokines including IFN-gamma. What is important is that IL-10 production was not impaired in infected IL-27R(-/-) mice. Depletion of CD4(+) T cells in infected IL-27R(-/-) mice resulted in a dramatically reduced production of IFN-gamma, preventing the early mortality of infected IL-27R(-/-) mice. This was accompanied by a significantly reduced inflammatory response and a major amelioration of liver pathology. These results could be mimicked by treating IL-27R(-/-) mice with a neutralizing anti-IFN-gamma antibody. Thus, our data identify IL-27 signaling as a novel pathway to prevent early mortality via inhibiting hyperactivation of CD4(+) Th1 cells and their excessive secretion of IFN-gamma during infection with African trypanosomes. These data are the first to demonstrate the essential role of IL-27 signaling in regulating immune responses to extracellular protozoan infections

Evaluation of prognostic risk models for postoperative pulmonary complications in adult patients undergoing major abdominal surgery: a systematic review and international external validation cohort study

Background Stratifying risk of postoperative pulmonary complications after major abdominal surgery allows clinicians to modify risk through targeted interventions and enhanced monitoring. In this study, we aimed to identify and validate prognostic models against a new consensus definition of postoperative pulmonary complications. Methods We did a systematic review and international external validation cohort study. The systematic review was done in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched MEDLINE and Embase on March 1, 2020, for articles published in English that reported on risk prediction models for postoperative pulmonary complications following abdominal surgery. External validation of existing models was done within a prospective international cohort study of adult patients (≥18 years) undergoing major abdominal surgery. Data were collected between Jan 1, 2019, and April 30, 2019, in the UK, Ireland, and Australia. Discriminative ability and prognostic accuracy summary statistics were compared between models for the 30-day postoperative pulmonary complication rate as defined by the Standardised Endpoints in Perioperative Medicine Core Outcome Measures in Perioperative and Anaesthetic Care (StEP-COMPAC). Model performance was compared using the area under the receiver operating characteristic curve (AUROCC). Findings In total, we identified 2903 records from our literature search; of which, 2514 (86·6%) unique records were screened, 121 (4·8%) of 2514 full texts were assessed for eligibility, and 29 unique prognostic models were identified. Nine (31·0%) of 29 models had score development reported only, 19 (65·5%) had undergone internal validation, and only four (13·8%) had been externally validated. Data to validate six eligible models were collected in the international external validation cohort study. Data from 11 591 patients were available, with an overall postoperative pulmonary complication rate of 7·8% (n=903). None of the six models showed good discrimination (defined as AUROCC ≥0·70) for identifying postoperative pulmonary complications, with the Assess Respiratory Risk in Surgical Patients in Catalonia score showing the best discrimination (AUROCC 0·700 [95% CI 0·683–0·717]). Interpretation In the pre-COVID-19 pandemic data, variability in the risk of pulmonary complications (StEP-COMPAC definition) following major abdominal surgery was poorly described by existing prognostication tools. To improve surgical safety during the COVID-19 pandemic recovery and beyond, novel risk stratification tools are required. Funding British Journal of Surgery Society