Timothy V. Johnson

Absolute Preoperative C-Reactive Protein Predicts Metastasis and Mortality in the First Year Following Potentially Curative Nephrectomy for Clear Cell Renal Cell Carcinoma

PURPOSE C-reactive protein is an inflammatory biomarker associated with tumor burden and metastasis in renal cell carcinoma. Recent studies suggest that preoperative C-reactive protein predicts metastasis and mortality after nephrectomy for localized renal cell carcinoma. However, these studies dichotomized C-reactive protein (typically 10 mg/l or greater vs less than 10 mg/l). Considering the continuous range of C-reactive protein (less than 1 mg/l to greater than 100 mg/l) we assessed the ability of absolute preoperative C-reactive protein to predict metastases and mortality as a continuous variable. MATERIALS AND METHODS Patients with clinically localized (T1-T3N0M0) clear cell renal cell carcinoma were followed for 1 year postoperatively. Metastases were identified radiologically and mortality was determined by death certificate. Univariate and multivariate binary logistic regression analyses examined 1-year relapse-free survival and overall relative survival across patient and disease characteristics. RESULTS Of the 130 patients in this study metastases developed in 24.6% and 10.8% of the patients died. Mean (SD) preoperative C-reactive protein for patients in whom metastases did and did not develop was 89.17 (74.17) and 9.16 (30.62) mg/l, respectively. Mean preoperative C-reactive protein for patients who did and did not die was 102.61 (77.32) and 19.52 (46.10) mg/l, respectively. On multivariate analysis SSIGN score (p <0.001) and preoperative C-reactive protein (B 0.027, SE 0.003, p <0.001) were significant predictors of relapse-free survival, and preoperative platelets (p = 0.009) and preoperative C-reactive protein (B 0.011, SE 0.008, p <0.001) were significant predictors of overall relative survival. CONCLUSIONS Absolute preoperative C-reactive protein is a robust predictor of metastasis and mortality after nephrectomy for localized renal cell carcinoma. Clinicians should consider absolute preoperative C-reactive protein to identify high risk patients for closer surveillance or additional therapy. In addition, predictive algorithms and models of metastasis should consider incorporating C-reactive protein as a continuous variable to maximize predictive ability.

Extensive Inguinal Lymphadenectomy Improves Overall 5-Year Survival in Penile Cancer Patients: Results From the Surveillance, Epidemiology, and End Results Program

European Urological Association guidelines recommend potentially curative inguinal lymphadenectomy for certain cases of penile cancer such as grade 3 and pT2‐4 lesions, among others. Anecdotally, the authors have noticed that few patients undergo inguinal lymphadenectomy. Therefore, they assessed the frequency of inguinal lymphadenectomy and the impact of dissection extent on survival using the Surveillance, Epidemiology, and End Results (SEER) database.

Review of the Relationship between C-Reactive Protein and Exercise

C-reactive protein (CRP), an acute phase reactant, is associated with systemic inflammation. Many studies have demonstrated that CRP levels have important prognostic implications for patients. For example, individuals with elevated CRP levels have an increased risk of cardiovascular events. The JUPITER study showed that reducing CRP levels can mitigate this risk. Various trials have investigated the effect of lifestyle modifications on serum CRP levels. Specifically, the impact of different exercise-based protocols on CRP levels has been researched. This review article evaluates the response of CRP levels to aerobic-based, resistance-based, and combination exercise protocols. Furthermore, it examines the impact of such regimens in children, adults, and the elderly.No definitive answers exist regarding the relationship between exercise and CRP levels. Significant reductions in CRP levels were noted in 11 of 25 trials of aerobic-based regimens, two of five studies of combination protocols, and neither of two trials of resistance-based regimens. Similar findings were seen across all age groups. There were significant CRP reductions in nine of 18 adult studies, four of ten child studies, and one of three elderly studies. Mixed results reflect uncertainty about the ability of exercise to reduce inflammation. Various mechanisms, including increased protein synthesis and fat loss, have been proposed to explain the potential anti-inflammatory effects of exercise.While exercise-based regimens have produced inconsistent results, lifestyle modifications do appear to have significant anti-inflammatory effects. This was particularly evident in studies that utilized combined diet/exercise programs. Significant CRP reductions were seen in five of seven such trials. Interestingly, both studies with failed combination protocols achieved substantial CRP reductions in their diet-only groups. These findings suggest that weight loss is important in reducing inflammation. Additionally, they indicate that combined diet/exercise protocols should be part of any lifestyle intervention program. Further research will be needed to identify optimal regimens for achieving anti-inflammatory benefits.

Postoperative Better Than Preoperative C-reactive Protein at Predicting Outcome After Potentially Curative Nephrectomy for Renal Cell Carcinoma

OBJECTIVES Preoperative C-reactive protein (CRP) predicts metastasis and mortality in localized renal cell carcinoma (RCC). However, the predictive potential of after resection of localized RCC remains unclear. Therefore, we assessed the absolute ability of postoperative CRP to predict metastases and mortality as a continuous variable. METHODS Patients with clinically localized (T1-T3N0M0) clear-cell RCC were followed for 1 year postoperatively. Metastases were identified radiologically and mortality by death certificate. Univariate and multivariate binary logistic regression analyses examined 1 year relapse-free survival (RFS) and overall survival (OS) across patient and disease characteristics. RESULTS Of the 110 patients in this study, 16.4% developed metastases and 6.4% died. Mean (SD) postoperative CRP for patients who did and did not develop metastases were 69.06 (73.55) mg/L and 5.27 (7.80), respectively. Mean (SD) postoperative CRP for patients who did and did not die were 89.31 (69.51) mg/L and 10.88 (30.32), respectively. In multivariate analysis, T-stage (OR: 12.452, 95% CI: 2.889-53.660) and postoperative CRP ((B: .080, SE: .025; P < .001) were significant predictors of RFS. T-Stage (OR: 11.715; 95% CI: 1.102-124.519) and postoperative CRP (B: .017; SE: .007; P < .001) were also significant predictors of OS. After adjusting for postoperative CRP, preoperative CRP was not predictive of these outcomes. CONCLUSIONS Postoperative, not preoperative, CRP is the better predictor of metastasis and mortality following nephrectomy for localized RCC. Clinicians should consider absolute postoperative CRP to identify high-risk patients for closer surveillance or additional therapy. Predictive algorithms should consider incorporating postoperative CRP as a continuous variable to maximize predictive ability.

Preoperative Erythrocyte Sedimentation Rate Independently Predicts Overall Survival in Localized Renal Cell Carcinoma following Radical Nephrectomy

Objectives. To determine the relationship between preoperative erythrocyte sedimentation rate (ESR) and overall survival in localized renal cell carcinoma (RCC) following nephrectomy. Methods. 167 patients undergoing nephrectomy for localized RCC had ESR levels measured preoperatively. Receiver Operating Characteristics curves were used to determine Area Under the Curve and relative sensitivity and specificity of preoperative ESR in predicting overall survival. Cut-offs for low (0.0–20.0 mm/hr), intermediate (20.1–50.0 mm/hr), and high risk (>50.0 mm/hr) groups were created. Kaplan-Meier analysis was conducted to assess the univariate impact of these ESR-based groups on overall survival. Univariate and multivariate Cox regression analysis was conducted to assess the potential of these groups to predict overall survival, adjusting for other patient and tumor characteristics. Results. Overall, 55.2% were low risk, while 27.0% and 17.8% were intermediate and high risk, respectively. Median (95% CI) survival was 44.1 (42.6–45.5) months, 35.5 (32.3–38.8) months, and 32.1 (25.5–38.6) months, respectively. After controlling for other patient and tumor characteristics, intermediate and high risk groups experienced a 4.5-fold (HR: 4.509, 95% CI: 0.735–27.649) and 18.5-fold (HR: 18.531, 95% CI: 2.117–162.228) increased risk of overall mortality, respectively. Conclusion. Preoperative ESR values represent a robust predictor of overall survival following nephrectomy in localized RCC.

Patient misunderstanding of the individual questions of the American Urological Association symptom score.

PURPOSE Lower urinary tract symptoms are often assessed using the American Urological Association symptom score. However, some patients may experience difficulty completing the AUA questionnaire. We hypothesized that certain individual questions may generate more misunderstanding than others. MATERIALS AND METHODS This study involved patients at 2 hospitals who completed the American Urological Association symptom score twice, that is 1) self-administered and 2) physician assisted. Analyses compared self-reported and physician obtained responses to each individual question. One-way ANOVA with the Tukey HSD post hoc test was done to assess whether mean disagreements between self-reported and physician administered American Urological Association symptom scores differed significantly by patient education level. RESULTS The study group consisted of 998 patients. For each symptom score question we found an inverse relationship between education level and symptom misrepresentation. This discrepancy was the largest for questions on frequency (question 2) and urgency (question 4), which are related to irritative symptoms. Mean misrepresentation of the total American Urological Association symptom score was 2.42 and 5.33 for patients with greater than 12 and fewer than 9 years of education, respectively (p <0.001). Of patients with more than 12 years of education 28% misreported their symptoms by 4 points or greater and 1% misreported them by 10 points or greater, while 58% with fewer than 9 years of education misreported their total score by 4 points or greater and 21% misreported it by greater than 10 points. CONCLUSIONS While the American Urological Association symptom score is a useful tool for the rapid diagnosis of benign prostatic hyperplasia, patients with low education misrepresent their scores more often and to a higher degree, possibly predisposing them to inappropriate care.

Systematic Review of the Evidence of a Relationship Between Chronic Psychosocial Stress and C-Reactive Protein

IntroductionC-reactive protein (CRP) is an acute-phase reactant with an increasing number of clinical functions. Studies in recent years have identified several social, economic, demographic, and psychological factors that contribute to baseline inflammation. Psychosocial stress represents a significant contributor to baseline inflammation. Given the importance of understanding background drivers of CRP levels, we conducted this review to assess the impact of chronic psychosocial stress on CRP levels.MethodsMedline was searched through February 2013 for human studies examining CRP levels with respect to chronic psychosocial stress.ResultsThe initial search identified 587 articles from which 129 potentially appropriate articles were reviewed. Of these 129 articles, 41 articles were included in the review. These studies were published between 2003 and 2013. Of these studies, 6 analyzed employment stress, 2 analyzed unemployment stress, 6 analyzed burnout and vital exhaustion, 6 analyzed caregiver stress, 3 analyzed interpersonal stress, 17 analyzed socioeconomic position, and 2 analyzed discrimination.ConclusionWe conclude that psychosocial stress significantly impacts CRP and should be considered when interpreting the meaning of CRP elevations.

Exercise is Associated with Better Erectile Function in Men Under 40 as Evaluated by the International Index of Erectile Function

INTRODUCTION Studies have shown an association between erectile dysfunction and sedentary lifestyle in middle-aged men, with a direct correlation between increased physical activity and improved erectile function. Whether or not this relationship is present in young, healthy men has yet to be demonstrated. AIM The aim of this study was to assess the association between physical activity and erectile function in young, healthy men. MAIN OUTCOME MEASURES The primary end points for our study were: (i) differences in baseline scores of greater than one point per question for the International Index of Erectile Function (IIEF); (ii) differences in baseline scores of greater than one point per question for each domain of the IIEF; (iii) exercise energy expenditure; and (iv) predictors of dysfunction as seen on the IIEF. METHODS The participants were men between the ages of 18 and 40 years old at an academic urology practice. Patients self-administered the Paffenbarger Physical Activity Questionnaire and the IIEF. Patients were stratified by physical activity into two groups: a sedentary group (≤1,400 calories/week) and an active group (>1,400 calories/week). Men presenting for the primary reason of erectile dysfunction or Peyronies disease were excluded. RESULTS Seventy-eight patients had complete information in this study: 27 patients (34.6%) in the sedentary group (≤1,400 kcal/week) and 51 patients (65.4%) in the active group (>1,400 kcal/week). Sedentary lifestyle was associated with increased dysfunction in the following domains of the IIEF: erectile function (44.4% vs. 21.6%, P = 0.04), orgasm function (44.4% vs. 17.7%, P = 0.01), intercourse satisfaction (59.3% vs. 35.3%, P = 0.04), and overall satisfaction (63.0% vs. 35.3%, P = 0.02). There was a trend toward more dysfunction in the sedentary group for total score on the IIEF (44.4% vs. 23.5%, P = 0.057), while sexual desire domain scores were similar in both groups (51.9% vs. 41.2%, P = 0.37). CONCLUSIONS We have demonstrated that increased physical activity is associated with better sexual function measured by a validated questionnaire in a young, healthy population. Further studies are needed on the long-term effects of exercise, or lack thereof, on erectile function as these men age.

Peak window of suicides occurs within the first month of diagnosis: implications for clinical oncology

Objective: A diagnosis of cancer can provoke painful emotional reactions and possibly suicidal thoughts in a patient. Consequently, cancer patients carry a twofold increased lifetime risk of suicide. This risk is much higher within 1 year of diagnosis. However, it remains largely unknown whether suicide frequency remains constant within the first year. Therefore, we sought to characterize the distribution of suicides in order to potentially identify a clinically important window of peak suicide risk.

Multimedia Version of a Standard Medical Questionnaire Improves Patient Understanding Across All Literacy Levels

PURPOSE Low health literacy is a significant problem in the United States. At the same time written screening tools such as the American Urological Association symptom score are used more frequently at hospitals and clinics. We previously reported that many patients do not fully understand this tool and often provide inaccurate information. To combat this problem we developed a novel multimedia version of the American Urological Association symptom score. MATERIALS AND METHODS In this randomized, controlled trial we divided 232 patients into a control arm that self-administered the traditional written version of the symptom score and an experimental arm that self-administered the new multimedia version. Patients in each arm were later administered the tool a second time by an interviewer for comparison. Using multivariate analysis we measured disagreement between the self-administered and interviewer administered scores, and compared the 2 arms. RESULTS Patients assigned the written and the multimedia version showed an average error of 3.48 and 1.97, respectively (p <0.001), for a 43% decrease. Improvement was noted regardless of patient literacy. Errors by patients with low and high literacy decreased from 4.55 to 2.24 and 3.10 to 1.86 (p = 0.03 and <0.001, respectively). CONCLUSIONS As a model, the American Urological Association symptom score multimedia version represents an exciting opportunity to improve many other written screening tools since it increased understanding and decreased scoring errors across all literacy levels, possibly allowing physicians to treat patients more effectively.