Evaluating the size criterion for PI-RADSv2 category 5 upgrade: is 15 mm the best threshold?

Purpose

The purpose of the study was to determine if the ≥ 15 mm threshold currently used to define PIRADS 5 lesions is the optimal size threshold for predicting high likelihood of clinically significant (CS) cancers.

Materials

Three hundred and fifty-eight lesions that may be changed from category 4 to 5 or vice versa on the basis of the size criterion (category 4: n = 288, category 5: n = 70) from 255 patients were evaluated. Kendall’s tau-b statistic accounting for inter-lesion correlation, generalized estimation equation logistic regression, and receiver operating curve analysis evaluated two lesion size-metrics (lesion diameter and relative lesion diameter—defined as lesion diameter/prostate volume) for ability to identify CS (Gleason grade ≥ 3 + 4) cancer at targeted biopsy. Optimal cut-points were identified using the Youden index. Analyses were performed for the whole prostate (WP) and zone-specific sub-cohorts of lesions in the peripheral and transition zones (PZ and TZ).

Results

Lesion diameter showed a modest correlation with Gleason grade (WP: τB = 0.21, p < 0.0001; PZ: τB = 0.13, p = 0.02; TZ: τB = 0.32, p = 0.001), and association with CS cancer detection (WP: AUC = 0.63, PZ: AUC = 0.59, TZ: AUC = 0.74). Empirically derived thresholds (WP: 14 mm, PZ: 13 mm, TZ: 16 mm) performed similarly to the current ≥ 15 mm standard. Lesion relative lesion diameter improved identification of CS cancers compared to lesion diameter alone (WP: τB = 0.30, PZ: τB = 0.24, TZ: τB = 0.42, all p < 0.0001). AUC also improved for WP and PZ lesions (WP: AUC = 0.70, PZ: AUC = 0.68, and TZ: AUC = 0.74).

Conclusions

The current ≥ 15 mm diameter threshold is a reasonable delineator of PI-RADS category 4 and category 5 lesions in the absence of extraprostatic extension to predict CS cancers. Additionally, relative lesion diameter can improve identification of CS cancers and may serve as another option for distinguishing category 4 and 5 lesions.

     

Hepatic Hemodynamic Changes Following Stepwise Liver Resection

Aim

Extended liver resection has increased during the last decades. However, hepatic hemodynamic changes after resection and the consequent complications like post hepatectomy liver failure are still a challenging issue. The aim of this study was to systematically evaluate the role of stepwise liver resection on hepatic hemodynamic changes.

Methods

To evaluate this effect we performed 25, 50, and 75 % sequential liver resections in 10 pigs. Before and after each resection, the hepatic artery flow and portal vein flow in relation to the remnant liver volume (RLV) as well as hepatic vascular pressures were measured and compared between the groups.

Results

Following sequential liver resection, the hepatic artery flow /100 g decreases and the portal vein flow increases up to 17 and 167 % following extended liver resection (75 %), respectively. Also, during stepwise liver resection, the portal vein pressure increases gradually up to 33 % following extended hepatectomy (75 %).

Conclusion

Sequential decrease in the RLV decreases the hepatic artery flow /100 g and increases the portal vein flow /100 g and portal vein pressure. As the consequence, the liver goes under more poor-oxygenated blood supply and higher pressure. This may be one of the most important mechanisms of the post hepatectomy liver failure in case of extended liver resection.

     

Electrode adsorption method for determination of enzymatic activity

The paper describes an electrical method for the determination of enzymatic activity. It is based on the fact that certain peptides, which are hydrolysed by enzymes, adsorb on a metal electrode in such a way that the double-layer capacitance of the electrode is changed. The two parts of the hydrolysed peptide do not have this property. The capacitance change depends on the concentration of the peptide and can be used to measure it. We describe more specifically the use of the tripeptide Bz-Phe-Val-Arg-pNA, which is a substrate for enzymes like thrombin and trypsin. Some different ways to use the electrode method are described. The determination of antithrombin activity in plasma and whole blood is taken as a practical example. The necessary instrumentation is briefly described with special attention to an automated equipment, which controls the experimental conditions and reduces errors due to the operator. Experimental results from studies of the frequency dispersion of the electrode impedance are presented. A model for the influence of the adsorbed peptides on the electrical properties of the electrode is derived. Finally, some general remarks are made about the applicability of the electrode adsorption method.     

Functional status,healthcare utilization,and the costs of liver transplantation

The Model for End‐Stage Liver Disease (MELD) score predicts higher transplant healthcare utilization and costs; however, the independent contribution of functional status towards costs is understudied. The study objective was to evaluate the association between functional status, as measured by Karnofsky Performance Status (KPS), and liver transplant (LT) costs in the first posttransplant year. In a cohort of 598 LT recipients from July 1, 2009 to November 30, 2014, multivariable models assessed associations between KPS and outcomes. LT recipients needing full assistance (KPS 10%‐40%) vs being independent (KPS 80%‐100%) were more likely to be discharged to a rehabilitation facility after LT (22% vs 3%) and be rehospitalized within the first posttransplant year (78% vs 57%), all P < .001. In adjusted generalized linear models, in addition to MELD (P < .001), factors independently associated with higher 1‐year post‐LT transplant costs were older age, poor functional status (KPS 10%‐40%), living donor LT, pre‐LT hemodialysis, and the donor risk index (all P < .001). One‐year survival for patients in the top cost decile was 83% vs 93% for the rest of the cohort (log rank P < .001). Functional status is an important determinant of posttransplant resource utilization; therefore, standardized measurements of functional status should be considered to optimize candidate selection and outcomes.     

Patient‐reported outcomes from SYNERGY,a randomized,double‐blind,multicenter study evaluating combinations of mirabegron and solifenacin compared with monotherapy and placebo in OAB patients

Aims

To evaluate patient‐reported outcomes (PROs) of combinations of solifenacin and mirabegron compared with solifenacin and mirabegron monotherapy and with placebo in patients with overactive bladder (OAB) from the SYNERGY trial.

Methods

Following a 4‐week placebo run‐in, period patients (≥18 years) with OAB were randomized 2:2:1:1:1:1 to receive solifenacin 5 mg + mirabegron 25 mg (combination 5 + 25 mg), solifenacin 5 mg + mirabegron 50 mg, (combination 5 + 50 mg), solifenacin 5 mg, mirabegron 25 mg, mirabegron 50 mg or placebo for 12 weeks, followed by a 2‐week washout period. At each visit, PROs related to quality of life, symptom bother, and treatment satisfaction were assessed, including OAB‐q Symptom Bother score, health‐related quality of life (HRQOL) Total score, treatment satisfaction‐visual analogue scale (TS‐VAS), and patient perception of bladder condition (PPBC) questionnaires.

Results

Overall, 3527 patients were randomized into the study, with 3494 receiving double‐blind treatment. At end of treatment (EoT), both combination groups showed greater improvements in OAB‐q Symptom Bother score compared with the monotherapy groups (nominal P < 0.001). Statistically significant improvements in HRQOL Total scores were observed in the combination groups versus monotherapy groups (P ≤ 0.002). For both combination groups, the OAB‐q Symptom Bother score responder rates at EoT were statistically significantly higher versus mirabegron monotherapy (P < 0.05). The mean adjusted changes from baseline to EoT for PPBC were greater in the combination groups compared with monotherapy groups.

Conclusions

PROs showed that combination therapy provided clear improvements and an additive effect for many HRQOL parameters, including OAB‐q Symptom Bother score, HRQOL Total score, and PPBC.     

Ruling out clinically significant prostate cancer with negative multi-parametric MRI

Purpose

To evaluate the negative predictive value (NPV) of a negative prostate multi-parametric magnetic resonance imaging (mpMRI) in ruling out clinically significant prostate upon 12-core systematic biopsy.

Methods

We retrospectively reviewed 114 men evaluated at our institution who underwent systematic 12-core biopsy within 1 year of a negative prostate mpMRI. Clinicopathologic features were evaluated and NPV was calculated for detection of clinically significant (Gleason ≥ 7) cancer. Regression analysis was performed to identify clinical predictors of biopsy outcome.

Results

Overall, 88 (77.2%) patients in our cohort had no cancer detected upon biopsy. The highest pathologic grade was Gleason 6 (3 + 3) in 22 (19.3%) patients, and Gleason ≥ 7 in 4 (3.6%) patients. NPV for detecting Gleason ≥ 7 cancer was 96.5% (95% CI 93.1–99.9%) in the entire negative MRI cohort, 100% in those who were prostate biopsy naïve (n = 20), 100% in those with a prior negative biopsy (n = 53), and 90% in those who have had a previous positive biopsy and on active surveillance (n = 41). Regression analysis identified no predictors of significant cancer in our cohort.

Conclusion

In our cohort of men with no lesions detected on prostate mpMRI, we found very low rates of clinically significant cancer on systematic 12-core biopsy. In the few patients who diagnosed with prostate cancer, the majority had low-risk disease and could remain on active surveillance. Although validation studies and greater sample size is needed before clinical recommendations can be made, our data suggest patients with negative mpMRI evaluated by experienced radiologists may avoid unnecessary prostate biopsy and potential overtreatment.

     

A new future of forensic Y-chromosome analysis: rapidly mutating Y-STRs for differentiating male relatives and paternal lineages

The panels of 9-17 Y-chromosomal short tandem repeats (Y-STRs) currently used in forensic genetics have adequate resolution of different paternal lineages in many human populations, but have lower abilities to separate paternal lineages in populations expressing low Y-chromosome diversity. Moreover, current Y-STR sets usually fail to differentiate between related males who belong to the same paternal lineage and, as a consequence, conclusions cannot be drawn on the individual level as is desirable for forensic interpretations. Recently, we identified a new panel of rapidly mutating (RM) Y-STRs, composed of 13 markers with mutation rates above 1 × 10(-2), whereas most Y-STRs, including all currently used in forensics, have mutation rates in the order of 1 × 10(-3) or lower. In the present study, we demonstrate in 604 unrelated males sampled from 51 worldwide populations (HGDP-CEPH) that the RM Y-STRs provide substantially higher haplotype diversity and haplotype discrimination capacity (with only 3 haplotypes shared between 8 of the 604 worldwide males), than obtained with the largest set of 17 currently used Y-STRs (Yfiler) in the same samples (33 haplotypes shared between 85 males). Hence, RM Y-STRs yield high-resolution paternal lineage differentiation and provide a considerable improvement compared to Yfiler. We also find in this worldwide dataset substantially less genetic population substructure within and between geographic regions with RM Y-STRs than with Yfiler Y-STRs. Furthermore, with the present study we provide enhanced data evidence that the RM Y-STR panel is extremely successful in differentiating between closely and distantly related males. Among 305 male relatives, paternally connected by 1-20 meiotic transfers in 127 independent pedigrees, we show that 66% were separated by mutation events with the RM Y-STR panel whereas only 15% were with Yfiler; hence, RM Y-STRs provide a statistically significant 4.4-fold increase of average male relative differentiation relative to Yfiler. The RM Y-STR panel is powerful enough to separate closely related males; nearly 50% of the father and sons, and 60% of brothers could be distinguished with RM Y-STRs, whereas only 7.7% and 8%, respectively, with Yfiler. Thus, by introducing RM Y-STRs to the forensic genetic community we provide important solutions to several of the current limitations of Y chromosome analysis in forensic genetics.