Angiotensin-Converting Enzyme Inhibitor,Captopril, Improves Scar Healing in Hypertensive Rats

Pathological cutaneous scars, with aberrant extracellular matrix accumulation, have multiple origins. Antihypertensive medications, such as calcium channel blockers, have been used to treat pathological scars. However, a relationship between angiotensin-converting enzyme (ACE) inhibitors, pathological scars, and blood pressure (BP) has never been reported. Here, we aimed to compare the differences in scar development and the effects of the administration of systemic ACE inhibitor on scar tissue in a normotensive rat, the Wistar Kyoto rat (WKY), a hypertensive rat, and the spontaneously hypertensive rat (SHR). Using an 8-mm punch, we created two full-thickness skin defects in a total of 32 rats (16 WKY and 16 SHR) to obtain a total of 64 wounds. We established control WKY (n = 16), captopril-treated WKY (n = 16), control SHR (n = 16), and captopril-treated SHR (n = 16) groups and started captopril (100 mg/g per day) treatment on day 21 in the appropriate groups. The BP of all groups was measured at 0, 3, and 5 weeks. The scar area was measured by histopathological examination, and scarring was expressed in terms of scar area and fibroblast and capillary counts. The expression of heat shock protein (HSP) 47, type I and III collagens, alpha-smooth muscle actin (α-SMA), Ki67, and vascular endothelial growth factor (VEGF) was investigated using immunohistochemistry. The scar area and fibroblast count were significantly higher in control SHR than in control WKY. The scar area, fibroblast count, and capillary count were significantly smaller in captopril-treated SHR than in control SHR. Immunostaining for α-SMA, Ki67, and VEGF also showed a noticeable decrease in scarring in the treated SHR compared with that in control SHR. Thus, BP affects scar development in a rat model, and an ACE inhibitor is more effective at reducing scars in hypertensive rats than in normotensive rats.     

Charlson Comorbidity Index Is an Important Prognostic Factor for Long-Term Survival Outcomes in Korean Men with Prostate Cancer after Radical Prostatectomy

Purpose

To analyze overall survival (OS), prostate cancer (PCa)-specific survival (PCaSS), and non-PCaSS according to the Charlson Comorbidity Index (CCI) after radical prostatectomy (RP) for PCa.

Materials and Methods

Data from 336 patients who had RP for PCa between 1992 and 2005 were analyzed. Data included age, preoperative prostate-specific antigen (PSA), prostate volume, clinical stage, and pathologic stage. Pre-existing comorbidities were evaluated by the CCI, and patients were classified into two CCI score categories (0, ≥1).

Results

The mean age of patients was 64.31±6.12 years. The median PSA value (interquartile range, IQR) was 11.30 (7.35 and 21.02) ng/mL with a median follow-up period (IQR) of 96.0 (85.0 and 121.0) months. The mean CCI was 0.28 (0-4). Five-year OS, PCaSS, and non-PCaSS were 91.7%, 96.3%, and 95.2%, respectively. Ten-year OS, PCaSS, and non-PCaSS were 81.9%, 92.1%, and 88.9%, respectively. The CCI had a significant influence on OS (p=0.022) and non-PCaSS (p=0.008), but not on PCaSS (p=0.681), by log-rank test. In multivariate Cox regression analysis, OS was independently associated with the CCI [hazard ratio (HR)=1.907, p=0.025] and Gleason score (HR=2.656, p<0.001). PCaSS was independently associated with pathologic N stage (HR=2.857, p=0.031), pathologic T stage (HR=3.775, p=0.041), and Gleason score (HR=4.308, p=0.001). Non-PCaSS had a significant association only with the CCI (HR=2.540, p=0.009).

Conclusion

The CCI was independently associated with both OS and non-PCaSS after RP, but the CCI had no impact on PCaSS. The comorbidities of a patient should be considered before selecting RP as a curative modality for PCa.     

A comparison between central blood pressure values obtained by the Gaon system and the SphygmoCor system

Central pulse pressure is correlated with carotid atherosclerosis and the incidence of cardiovascular events more significantly than brachial pulse pressure. Augmentation index (Aix) has been shown to be an independent predictor of cardiovascular morbidity and mortality. Pulse wave analysis using the Gaon system allows for the estimation of central blood pressure (CBP), corrected augmentation index (Aix@HR75), ejection duration (ED) and subendocardial viability ratio (SEVR), and is widely used in clinical research in Korea. However, the accuracy of this system is controversial. From February 2008 to March 2011, 99 patients were recruited for this study. Measurements were taken both by the Gaon system and the SphygmoCor system on the same day for all study participants. The estimated values of CBP, Aix@HR75, ED and SEVR for the two systems were compared using paired t-tests, simple correlation analyses and Bland-Altman plots. Systolic blood pressure (SBP) estimated by the two systems was significantly (P<0.001) correlated; the coefficient was 0.982. The two s.d. of the difference in SBP between these systems was quite small--<7?mm?Hg. Aix@HR75, ED and SEVR as estimated by the two systems were also significantly correlated, although they, especially SEVR, showed much weaker correlations than were observed in SBP: coefficients for Aix@HR75, ED and SEVR were 0.727, 0.648 and 0.230, respectively. We assessed the CBP of Korean patients estimated by the two systems and observed that the correlations of Aix, ED and SEVR were weaker than that of CBP. Such variations may be due to the difference in measuring methods between the devices. As even a slight change in pulse waveforms may result in a large difference in estimations, parameters, including Aix@HR75, ED and SEVR, should be carefully interpreted by experienced clinicians.     

External validation of the RENAL nephrometry score nomogram for predicting high-grade renal cell carcinoma in solid, enhancing, and small renal masses

Purpose

To confirm predictive accuracies of the RENAL nephrometry score (RNS) nomogram for identifying malignancy and high-grade renal cell carcinoma (RCC) in an external cohort of small renal masses (SRMs).

Methods

A total of 1,129 patients who underwent extirpative renal surgery for solid and enhancing cT1 renal tumors between 2005 and 2012 at a single institution were included in the validation cohort. A single uro-radiologist utilized computed tomography image reconstruction to classify tumors according to the RNS. The area under the curve (AUC) and calibration plots were used to determine predictive accuracies of malignancy and high-grade models of the RNS nomogram.

Results

Malignant and high-grade tumors were identified in 1,012 (89.6 %) and 389 (38.4 %) patients with cT1 tumors, and in 658 (87.3 %) and 215 (32.6 %) patients with cT1a tumors, respectively. Predictive performances of the nomogram for malignancy and high-grade models revealed AUCs of 0.722 and 0.574 for cT1 tumors, and 0.727 and 0.495 for cT1a tumors, respectively. The predictive value of the malignancy model was comparable to that of the model-development cohort (AUC = 0.76); however, the predictive value of the high-grade model was inferior to that of the model-development cohort (AUC = 0.73).

Conclusions

Unlike previous validation studies, we report inferior predictive performance of the RNS nomogram for discriminating high-grade RCC in solid and enhancing SRMs. This suggests that the RNS nomogram may be unreliable for preoperatively predicting high-grade RCC in SRMs, in which tumor size, the key determinant of high-grade RCC, is a limiting factor.