Kiran Gollapudi

Correlates of Bother Following Treatment for Clinically Localized Prostate Cancer

PURPOSE We determined factors associated with bother, the distress patients experience as a result of functional detriments after treatment for localized prostate cancer. MATERIALS AND METHODS A prospective cohort of men treated for clinically localized prostate cancer completed a questionnaire comprising the UCLA-PCI, Medical Outcomes Study Short Form-36, American Urological Association Symptom Index and Memorial Anxiety Scale for Prostate Cancer fear of recurrence subscale. We used nonlinear mixed models to identify factors associated with severe urinary, sexual and bowel bother. RESULTS Worse function scores were associated with severe urinary, sexual and bowel bother following treatment (OR 0.88-0.94, p <0.001). Worse American Urological Association Symptom Index score was associated with severe urinary bother (OR 1.22, 95% CI 1.16-1.28). Time since treatment was inversely associated with urinary (OR 0.68, 95% CI 0.54-0.83) and bowel bother (OR 0.63, 95% CI 0.47-0.80) early after treatment but not for the entire 48-month study period. Receipt of concomitant androgen deprivation therapy was not associated with bother 48 months after radiation. CONCLUSIONS Addressing functional detriment may confer improvement in urinary, sexual and bowel bother. Patient distress related to dysfunction improves with time. Measuring health related quality of life after prostate cancer treatment should incorporate functional and bother assessments.

Effect of a low-fat fish oil diet on proinflammatory eicosanoids and cell-cycle progression score in men undergoing radical prostatectomy.

We previously reported that a 4- to 6-week low-fat fish oil (LFFO) diet did not affect serum insulin-like growth factor (IGF)-1 levels (primary outcome) but resulted in lower omega-6 to omega-3 fatty acid ratios in prostate tissue and lower prostate cancer proliferation (Ki67) as compared with a Western diet. In this post hoc analysis, the effect of the LFFO intervention on serum pro-inflammatory eicosanoids, leukotriene B4 (LTB4) and 15-S-hydroxyeicosatetraenoic acid [15(S)-HETE], and the cell-cycle progression (CCP) score were investigated. Serum fatty acids and eicosanoids were measured by gas chromatography and ELISA. CCP score was determined by quantitative real-time reverse transcriptase PCR (RT-PCR). Associations between serum eicosanoids, Ki67, and CCP score were evaluated using partial correlation analyses. BLT1 (LTB4 receptor) expression was determined in prostate cancer cell lines and prostatectomy specimens. Serum omega-6 fatty acids and 15(S)-HETE levels were significantly reduced, and serum omega-3 levels were increased in the LFFO group relative to the Western diet group, whereas there was no change in LTB4 levels. The CCP score was significantly lower in the LFFO compared with the Western diet group. The 15(S)-HETE change correlated with tissue Ki67 (R = 0.48; P < 0.01) but not with CCP score. The LTB4 change correlated with the CCP score (r = 0.4; P = 0.02) but not with Ki67. The LTB4 receptor BLT1 was detected in prostate cancer cell lines and human prostate cancer specimens. In conclusion, an LFFO diet resulted in decreased 15(S)-HETE levels and lower CCP score relative to a Western diet. Further studies are warranted to determine whether the LFFO diet antiproliferative effects are mediated through the LTB4/BLT1 and 15(S)-HETE pathways. Cancer Prev Res; 7(1); 97–104. ©2013 AACR.

Body mass index in ambulatory cerebral palsy patients

Malnutrition is a common problem in children with cerebral palsy. Although malnutrition is often recognized in patients with severe cerebral palsy, it can be unrecognized in less severely affected patients. The consequences of malnutrition are serious, and include decreased muscle strength, poor immune status, and depressed cerebral functioning. Low body mass index has been used as a marker for malnutrition. The purpose of this study was to determine which patients in an ambulatory cerebral palsy patient population were at risk for low body mass index. A retrospective chart review was performed on 75 patients. Age, sex, height, weight, type of cerebral palsy, and functional status [gross motor functional classification system (GMFCS) level] was recorded from the chart. Descriptive statistics with bivariate and multivariate regression analyses were performed. Thirty-eight boys and 37 girls with an average age of 8.11 years were included in the study. Unique to our patient population, all cerebral palsy patients were independent ambulators. Patients with quadriplegic cerebral palsy had a significantly lower body mass index than those with diplegic and hemiplegic cerebral palsy. Patients with a GMFCS III had significantly lower body mass index than those with GMFCS I and II. When multivariate regression analysis to control for age and sex was performed, low body mass index remained associated with quadriplegic cerebral palsy and GMFCS III. Malnutrition is a common health problem in patients with cerebral palsy, leading to significant morbidity in multiple organ systems. We found that in an ambulatory cerebral palsy population, patients with lower functional status or quadriplegia had significantly lower body mass index, suggesting that even highly functioning ambulatory cerebral palsy patients are at risk for malnutrition.

Reply to “Phase II prospective randomized trial of weight loss prior to radical prostatectomy”

BackgroundObesity is associated with poorly differentiated and advanced prostate cancer and increased mortality. In preclinical models, caloric restriction delays prostate cancer progression and prolongs survival. We sought to determine if weight loss (WL) in men with prostate cancer prior to radical prostatectomy affects tumor apoptosis and proliferation, and if WL effects other metabolic biomarkers.MethodsIn this Phase II prospective trial, overweight and obese men scheduled for radical prostatectomy were randomized to a 5–8 week WL program consisting of standard structured energy-restricted meal plans (1200–1500 Kcal/day) and physical activity or to a control group. The primary endpoint was apoptotic index in the radical prostatectomy malignant epithelium. Secondary endpoints were proliferation (Ki67) in the radical prostatectomy tissue, body weight, body mass index (BMI), waist to hip ratio, body composition, and serum PSA, insulin, triglyceride, cholesterol, testosterone, estradiol, leptin, adiponectin, interleukin 6, interleukin 8, insulin-like growth factor 1, and IGF binding protein 1.ResultsIn total 23 patients were randomized to the WL intervention and 21 patients to the control group. Subjects in the intervention group had significantly more weight loss (WL:−3.7 ± 0.5 kg; Control:−1.6 ± 0.5 kg; p = 0.007) than the control group and total fat mass was significantly reduced (WL:−2.1 ± 0.4; Control: 0.1 ± 0.3; p = 0.015). There was no significant difference in apoptotic or proliferation index between the groups. Among the other biomarkers, triglyceride, and insulin levels were significantly decreased in the WL compared with the control group.ConclusionsIn summary, this short-term WL program prior to radical prostatectomy resulted in significantly more WL in the intervention vs. the control group and was accompanied by significant reductions in body fat mass, circulating triglycerides, and insulin. However, no significant changes were observed in malignant epithelium apoptosis or proliferation. Future studies should consider a longer term or more intensive weight loss intervention.

Advanced skeletal maturity in ambulatory cerebral palsy patients.

Introduction: Both advanced and delayed bone age relative to chronological age have been described in non ambulatory children with moderate to severe cerebral palsy (CP). The purpose of our study was to assess skeletal maturation in an ambulatory CP population and determine the affects of body mass index (BMI), type of CP, and Gross Motor Function Classification System (GMFCS) on skeletal maturity. Methods: A retrospective chart and radiograph review was performed on 51 patients with ambulatory CP. A control group of 50 patients was also analyzed. Age, sex, height, weight, type of CP, and GMFCS were recorded from the chart. The height and weight were used to calculate BMI. Bone age was determined using the Oxford method. Statistical analysis for the data included descriptive statistics with bivariate and multivariate regression analyses. Significance was determined as P < 0.05. Results: There were 26 boys and 25 girls. All CP patients were independent ambulators. The mean chronological age was 7.1 years for boys and 8.6 years for girls. The mean bone age was 9.9 years for boys and 10.6 years for girls. Overall, 48 (94%) of 51 patients had advanced bone age compared with chronological age. Bone age was significantly advanced compared with chronological age for boys (P = 0.033) and showed a trend toward significance in girls (P = 0.079). Bone age was advanced compared with our control population in both sexes. In multivariate analysis, quadriplegic CP type showed a trend toward significance (P = 0.066), and GMFCS III was significantly associated with advanced bone age in boys (P = 0.011). In girls, quadriplegic CP type and BMI of less than 15 were significantly associated with advanced bone age (P < 0.05 in both). Conclusion: Our results demonstrated that most of the ambulatory CP patients had advanced bone age compared with chronological age. Quadriplegic CP type in boys and girls contributed to advanced bone age. GMFCS III and a low BMI also contributed to advanced bone age in boys and girls, respectively. Understanding factors that lead to either delayed or advanced skeletal maturation is important in planning the appropriate timing for orthopaedic surgical intervention.

Association between renal mass biopsy and upstaging to perinephric fat involvement in a contemporary cohort of patients with clinical T1a renal cell carcinoma

BACKGROUND Although tumor tract seeding from renal mass biopsy (RMB) is exceedingly rare, the possibility of tumor capsule violation from RMB leading to perinephric fat invasion has not been quantified. We evaluated the association between RMB and perinephric fat invasion in patients with clinical T1a renal cell carcinoma who underwent partial or radical nephrectomy. MATERIALS AND METHODS We reviewed the National Cancer Database from 2010-2013 and identified patients who underwent surgery for clinical T1a tumors. Patients were classified as upstaged only if final pathology demonstrated perinephric invasion only (pT3a). Mixed-effect logistic regression analysis was performed on inverse probability weighted matched groups to identify predictors of perinephric fat invasion. Multivariable Cox proportional hazards models and Kaplan-Meier survival curves were used to evaluate overall survival (OS). RESULTS A total of 24,548 patients met our inclusion criteria. Pathologic upstaging to pT3a perinephric fat involvement occurred in 1.2% of patients. This rate of upstaging was 1.1% in the no biopsy group compared with 2.1% in patients who underwent RMB (P < 0.01). In multivariable logistic model, RMB was associated with pT3a perinephric fat upstaging (OR 1.69, 95% CI 1.17-2.44, P < 0.01). Upstaging to pT3a was also associated with worse OS (HR 1.71, 95% CI 1.13-2.60, P = 0.01). Kaplan-Meier survival curves demonstrated similar OS estimates in patients upstaged to pT3a disease, irrespective of undergoing RMB or not (Log-Rank = 0.87). CONCLUSION RMB was associated with increased rate of upstaging to pT3a perinephric fat involvement in clinical T1a RCC. This effect is small with unclear clinical significance. This is perhaps balanced by the importance of the information acquired from biopsies. Future studies are needed to elucidate clinical significance of this finding.

Blood in Urine

A 68-year-old Caucasian man presents to the emergency department complaining of blood in his urine as well as small blood clots for 3 days. He denies dysuria, nocturia, urinary frequency or hesitancy, or a decreased urinary stream. He denies any fevers, chills, or weight loss. He has had similar episodes of visible blood in his urine in the last several months and has been treated twice with antibiotics for a possible urinary tract infection without improvement. He has a history of hypertension for which he takes a beta-blocker; otherwise he has had no surgeries and takes no other medications. He denies any family history of malignancy or renal disease. He denies any history of trauma and does not vigorously exercise. He has a 40-pack-year history of smoking and worked as a painter. On physical exam, he is afebrile with normal vital signs. His abdomen is soft, without any palpable masses. His genitourinary exam reveals a normal circumcised phallus without lesions and normal bilateral descended testicles. On digital rectal exam, his prostate is small without any nodularity, induration, or tenderness. On laboratory exam, his hematocrit is 42 %, creatinine is 1.0 mg/dL, INR and PTT are normal, and PSA is 2 ng/dL. His urinalysis shows a large number of red cells, no white cells, no casts, and no bacteria.

Is There a Role for Medications to Reduce the Need for Prostate Biopsy

The widespread use of prostate-specific antigen (PSA) screening has led to an increased incidence of prostate cancer, and the majority of prostate cancer cases are now detected at an early stage (Cooperberg et al. J Urol 170: S21–5, 2003). PSA can be elevated due to a number of noncancer-related conditions including benign prostatic hyperplasia (BPH), inflammation, infection, and trauma. Also, the PSA value fluctuates, and an elevated PSA can normalize on subsequent measurements (Eastham et al. JAMA 289(20): 2695–700, 2003). The lack of PSA specificity becomes especially apparent when evaluating patients with a mildly elevated PSA. Only 25–35 % of men undergoing prostate biopsy in the PSA “gray zone” of 4–10 ng/ml are found to have prostate cancer, leaving behind a significant portion of patients who undergo potentially unnecessary biopsy (Brawer et al. J Urol 150(1): 106–9, 1993; Catalona et al. J Urol 151(5):1283–90, 1994). Though prostate biopsy is generally safe, it is an invasive procedure invoking patient anxiety and can be associated with complications such as pain, bleeding, sepsis, and possibly impotence (Aus et al. Br J Urol 77(6): 851–5, 1996; Rietbergen et al. Urology 49(6): 875–80, 1997; Fujita et al. J Urol 182(6): 2664–9, 2009). Furthermore, infectious complications from prostate biopsy are increasing in prevalence due to fluoroquinolone resistance (Feliciano et al. J Urol 179(3):952–5, 2008). Hence, the challenge facing the referring physician or urologist is to determine the most appropriate candidates for prostate biopsy among patients who present with an abnormal PSA.