Low clinical stage renal cell carcinoma: relevance of microvascular tumor invasion as a prognostic parameter

PURPOSE: Renal cell carcinoma is a tumor with unpredictable behavior and defining reliable prognostic factors would be extremely valuable in the clinical setting. Tumor stage, nuclear grade and tumor cell type are the main prognostic clinical parameters available. In this study we evaluated the role of microvascular involvement in the primary lesion for predicting tumor behavior in patients with low stage clinical disease. MATERIALS AND METHODS: A total of 95 patients with clinically localized renal cell carcinoma (stages T1-T2 Nx M0) underwent radical nephrectomy and/or nephron sparing surgery, and were followed for a median of 45 months. The impact of microvascular tumor invasion on disease progression and its correlation with known pathological outcomes (tumor size, nuclear grade and cell type) were studied. RESULTS: Microvascular tumor invasion was observed in 24 patients (25%), of whom 50% had disease recurrence. Of the 71 patients without microvascular invasion only 4 (6%) showed tumor recurrence. When microvascular invasion was correlated with other histological parameters, a significant statistical association was noted with tumor diameter, perirenal fat invasion, macroscopic extension to the renal vein, nuclear grade, lymph node metastasis and sarcomatous elements in the tumor. Multivariate analysis showed that microvascular invasion and the involvement of regional lymph nodes were independent predictors of disease recurrence. Concerning cancer specific survival, microvascular invasion and perirenal fat infiltration were the only factors related to death. CONCLUSIONS: Microvascular invasion is an independent and relevant clinical prognostic parameter for low clinical stage renal cell carcinoma.     

Obesity Is Associated with Increased Prostate Growth and Attenuated Prostate Volume Reduction by Dutasteride

Background

Although obesity has been associated with larger prostate volumes (PV), few studies have actually investigated whether obesity enhances PV growth, especially among men using 5α-reductase inhibitors.

Objective

To examine whether obesity is associated with enhanced PV growth measured by serial transrectal ultrasound (TRUS) measurements.

Design, setting, and participants

We conducted a secondary analysis of the REduction by DUtasteride of prostate Cancer Events (REDUCE) trial, which was originally aimed at cancer risk reduction among high-risk men with a single negative prestudy biopsy.

Intervention

Per-protocol randomization to placebo or dutasteride and mandatory TRUS-guided biopsies at 2 yr and 4 yr.

Outcome measurements and statistical analysis

Percentage change in PV at 2 yr and 4 yr from baseline. We tested its association with baseline body mass index (BMI) groups of <25, 25–29.9, and ≥30 kg/m² using multivariable linear regression. Secondarily, we tested whether BMI was associated with the likelihood of having no PV reduction among men randomized to dutasteride using multivariable logistic regression.

Results and limitations

Of 8122 participants, we analyzed 71.8% and 54.5% with complete 2-yr and 4-yr PV data, respectively. In multivariable analysis, men on placebo with BMI ≥30 versus <25 kg/m² had enhanced PV growth from baseline (at 2 yr: 17.0% vs 10.7%, p < 0.001; at 4 yr: 29.4% vs 20.1%; p = 0.001). Men on dutasteride with BMI ≥30 versus <25 kg/m² had attenuated PV reduction from baseline (at 2 yr: −14.3% vs −18.5%; p = 0.002; at 4 yr: −13.2% vs −19.3%; p = 0.001) and higher likelihood of having no PV reduction (at 2 yr: odds ratio [OR]: 1.44; 95% confidence interval [CI], 1.08–1.93; p = 0.014; at 4 yr: OR: 1.62; 95% CI, 1.18–2.22; p = 0.003). We found no significant interactions between BMI and dutasteride on PV change at 2 yr and 4 yr (p interaction ≥0.36). No clinical outcomes or effects of weight change were assessed.

Conclusions

Obesity enhanced PV growth and attenuated PV reduction by dutasteride. The null interaction between obesity and dutasteride for PV change implies that the effect of obesity on dutasteride-treated men is likely a combination of dutasteride-driven PV reduction with obesity-driven PV growth rather than decreased dutasteride efficacy.

ClinicalTrials.gov identifier

NCT00056407.     

Serum Testosterone and Dihydrotestosterone and Prostate Cancer Risk in the Placebo Arm of the Reduction by Dutasteride of Prostate Cancer Events Trial

Background

Findings of studies on the association between androgens and prostate cancer (PCa) are mixed. Androgens may affect prostate-specific antigen (PSA) levels, thereby influencing biopsy recommendations. Also, androgens may stimulate prostate growth at very low levels with no additional effects at higher levels (saturation model).

Objective

To test whether androgens were associated with PCa risk in the placebo arm of a prospective study in which biopsies were performed regardless of PSA level.

Design, setting, and participants

Of 8122 men in the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial, 4073 men (50.1%) received placebo. Key entry criteria were PSA 2.5–10 ng/ml and one prior negative biopsy.

Intervention

Per-protocol biopsies at 2 and 4 yr; for-cause biopsies at physician discretion.

Outcome measurements and statistical analysis

Multivariable logistic regression was used to test the association between baseline log-transformed testosterone and dihydrotestosterone (DHT) levels and the risk of detecting either PCa or low-grade PCa (Gleason score <6) compared with high-grade PCa (Gleason score >7). In secondary analysis, we stratified the analysis by low baseline androgen levels (testosterone <10 nmol/l; DHT <0.76 nmol/l) compared with normal baseline androgen levels.

Results and limitations

Of 4073 men, 3255 (79.9%) had at least one biopsy after randomization and were analyzed. Androgen levels tested continuously or by quintiles were generally unrelated to PCa detection or grade. PCa detection was similar among men with low compared with normal baseline testosterone levels (25.5% and 25.1%; p = 0.831). In secondary analysis, higher testosterone levels at baseline were associated with higher PCa detection (odds ratio: 1.23; 95% confidence interval, 1.06–1.43; p = 0.006) only if men had low baseline testosterone (<10 nmol/l). For men with normal baseline testosterone (≥10 nmol/l), higher testosterone levels at baseline were unrelated to PCa risk (p = 0.33). No association was found for DHT and PCa (all p > 0.85).

Conclusions

Baseline serum testosterone and DHT levels were unrelated to PCa detection or grade. Our findings of the lowest testosterone levels being associated with the lowest PCa risk with no further changes with higher testosterone support a saturation model but must be confirmed in future studies using an a priori defined hypothesis.

ClinicalTrials.gov identifier

NCT00056407.     

Quercetin ameliorates polychlorinated biphenyls‐induced testicular DNA damage in rats

Polychlorinated biphenyls (PCBs) are a group of environmental contaminants widely reported to cause gonadal toxicity in both humans and animals. This study investigated the amelioratory role of quercetin in PCBs‐induced DNA damage in male Wistar rats. Polychlorinated biphenyls were administered intraperitoneally at a dose of 2 mg kg^?1 alone or in combination with quercetin (orally) at 50 mg kg^?1 for 25 days. Quercetin modulation of PCBs‐induced gonadal toxicity was evaluated using selected oxidative stress indices, comet assay, measurement of DNA concentration and histology of the testes. Administration of PCBs alone caused a significant (P < 0.05) depletion in the total thiol level in testes of treated rats. Conversely, the levels of reactive oxygen species (ROS) and thiobarbituric acid reactive substances (TBARS) production were markedly elevated in testes of PCBs‐treated rats compared with control. Further, PCBs exposure produced statistically significant increases in DNA tail migration, degraded double‐stranded DNA (dsDNA) concentration and histological alterations of testes of the treated rats compared to control. Quercetin cotreatment significantly improved the testicular antioxidant status, decreased DNA fragmentation and restored the testicular histology, thus demonstrating the protective effect of quercetin in PCBs‐treated rats.     

Effect of Rest Interval Length on the Volume Completed During Upper Body Resistance Exercise

The purpose of the current study was to compare the workout volume (sets x resistance x repetitions per set) completed during two upper body resistance exercise sessions that incorporated 1 minute versus 3 minute rest intervals between sets and exercises. Twelve trained men completed two experimental sessions that consisted of 5 upper body exercises (i.e. barbell bench press, incline barbell bench press, pec deck flye, barbell lying triceps extension, triceps pushdown) performed for three sets with an 8-RM load. The two experimental sessions differed only in the length of the rest interval between sets and exercises; one session with a 1-minute and the other session with a 3-minute rest interval. The results demonstrated that for each exercise, significantly greater workout volume was completed when resting 3 minutes between sets and exercises (p < 0.05). These results indicate that during a resistance exercise session, if sufficient time is available, resting 3 minutes between sets and exercises allows greater workout volume for the upper body exercises examined.

Key points

• The length of the rest interval between sets is an important variable when designing a resistance exercise program and may vary depending on the characteristic being emphasized (i.e. maximal strength, hypertrophy, localized muscular endurance, power).
• Although acknowledged, this variable is rarely monitored precisely in field settings.
• Previous studies that examined rest interval lengths from 1 to 5 minutes between sets for single exercises demonstrated significant differences in repetition performance and the exercise volume completed.
• There is a need for further research to compare the workout volume (sets x resistance x repetitions per set) completed over an entire resistance exercise session with different rest intervals between sets.
• The results of the current study indicate that during a resistance exercise session, if sufficient time is available, resting 3 minutes between sets and exercises allows greater workout volume for the upper body exercises examined.

Key words: Recovery, fatigue, strength, muscle endurance, weight training, strength training     

Effects of the use of oral contraceptives on hip and knee kinematics in healthy women during anterior stair descent

Purpose

Our aim was to evaluate the effects of the use of oral contraceptives (OC) on the hip and knee kinematics of healthy women during anterior stair descent.

Methods

Forty volunteers aged from 18 to 26 years were divided into two groups: 1—Group of women who had used OC for at least 3 months prior to evaluation (n = 20) and 2—Group of women who did not use OC (n = 20). The knee flexion/extension and abduction/adduction, hip flexion/extension, abduction/adduction and medial/lateral rotation excursions (degrees) were calculated for the dominant (supporting) limb during anterior stair descent. T tests for independent samples were used to compare the kinematic differences between the groups (α = 0.05).

Results

No significant difference was verified between the groups regarding the maximum excursion of knee flexion (n.s.) and abduction (n.s.) or hip flexion (n.s.), adduction (n.s.) and medial rotation (n.s.). When considering the knee flexion at 50°, no significant difference was verified between the groups regarding the excursion of knee abduction (n.s.) or hip flexion (n.s.) adduction (n.s.) and medial/lateral rotation (n.s.).

Conclusion

These results suggest that the use of OC does not influence the hip and knee kinematics during anterior stair descent. Therefore, the role of this medication as a protective factor against anterior cruciate ligament injuries remains questionable.

Level of evidence

III.     

Validation of the Pelvic Organ Prolapse Quantification Index (POP-Q-I): a novel interpretation of the POP-Q system for optimization of POP research

Even though very precise at describing pelvic organ position, our criticism to the Pelvic Organ Prolapse Quantification (POP-Q) system is its limited ability to quantify the prolapse itself, since it still classifies prolapse into four stages, almost the same way as Baden and Walker (Clin Obstet Gynecol 15(4):1070-1072, 1972) did in 1972. As a result, the same grade can include a wide prolapse intensity range. The objective of this study was to assess inter-observer reliability in the Pelvic Organ Prolapse Quantification Index (POP-Q-I; Lemos et al., Int Urogynecol J 18(6):609-611, 2007) on a prospective randomized trial. Fifty consecutive women were prospectively examined by two members of the urogynecology staff, blinded to each other's results. Spearman's rank correlation was used to assess inter-observer reliability. Excellent correlation coefficients were observed, with an overall coefficient of 96.5% (CI: 0.889-1.042; p < 0.0001). The POP-Q-I is a method that makes POP research more efficient by directly measuring prolapse as a continuous variable, which is statistically more powerful than the categorical variables proposed by the POP-Q system. This study suggests that the POP-Q-I is applicable to clinical POP research.     

Mycophenolate mofetil vs. sirolimus in kidney transplant recipients receiving tacrolimus-based immunosuppressive regimen

Abstract:  Mycophenolate mofetil (MMF) and sirolimus (SRL) are effective immunosuppressive drugs with distinct safety profile.
Methods:  Kidney transplant recipients receiving tacrolimus (TAC)-based immunosuppressive regimen were randomized to receive fixed daily doses of MMF (2 g/d, n = 50) or SRL (one loading dose of 15 mg, 5 mg/d till day 7 and 2 mg/d thereafter, n = 50) without induction therapy.
Results:  No differences were observed in the incidence of the composite (biopsy-confirmed acute rejection, graft loss or death) end-point (18% vs. 16%, p = 1.000), biopsy confirmed acute rejection (12% vs. 14%, p = 1.000), one-yr patient (94% vs. 98%, p = 0.308), graft (92% vs. 98%, p = 0.168), and death-censored graft survival (98% vs. 100%, p = 0.317) comparing patients receiving MMF or SRL respectively. Patients receiving SRL showed worse safety outcomes, higher mean creatinine (1.6 ± 0.5 mg/dL vs. 1.4 ± 0.3 mg/dL, p = 0.007), higher proportion of patients with proteinuria (52.0% vs. 10.7%, p = 0.041), higher mean urinary protein concentrations (0.3 ± 0.5 g/L vs. 0.1 ± 0.2 g/L, p = 0.012), higher mean cholesterol concentration (217 mg/dL vs. 190 mg/dL, p = 0.030), and higher proportion of patients prematurely discontinued from randomized therapy (26% vs. 8%, p = 0.031).
Conclusion:  In patients receiving TAC, MMF produced similar efficacy but superior safety profile compared with SRL.     

A nonlinear model predictive control strategy for trajectory tracking of a four‐wheeled omnidirectional mobile robot

This paper presents a nonlinear model‐based predictive controller (NMPC) for trajectory tracking of a four‐wheeled omnidirectional mobile robot. Methods of numerical optimization to perform real‐time nonlinear minimization of the cost function are used. The cost function penalizes the robot's position error, the robot's orientation angle error, and the control effort. Experimental results of the trajectories following and the performances of the methods of optimization are presented. Copyright © 2007 John Wiley & Sons, Ltd.