Differences in Implementation Outcomes of a Shared Decision-Making Program for Men with Prostate Cancer between an Academic Medical Center and County Health Care System.

BACKGROUND: Shared decision making (SDM) has long been advocated as the preferred way for physicians and men with prostate cancer to make treatment decisions. However, the implementation of formal SDM programs in routine care remains limited, and implementation outcomes for disadvantaged populations are especially poorly described. We describe the implementation outcomes between academic and county health care settings. METHODS: We administered a decision aid (DA) for men with localized prostate cancer at an academic center and across a county health care system. Our implementation was guided by the Consolidated Framework for Implementation Research and the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework. We assessed the effectiveness of the DA through a postappointment patient survey. RESULTS: Sites differed by patient demographic/clinical characteristics. Reach (DA invitation rate) was similar and insensitive to implementation strategies at the academic center and county (66% v. 60%, P = 0.37). Fidelity (DA completion rate) was also similar at the academic center and county (77% v. 80%, P = 0.74). DA effectiveness was similar between sites, except for higher academic center ratings for net promoter for the doctor (77% v. 37%, P = 0.01) and the health care system (77% v. 35%, P = 0.006) and greater satisfaction with manner of care (medians 100 v. 87.5, P = 0.04). Implementation strategies (e.g., faxing of patients' records and meeting patients in the clinic to complete the DA) represented substantial practice changes at both sites. The completion rate increased following the onset of reminder calls at the academic center and the creation of a Spanish module at the county. CONCLUSIONS: Successful DA implementation efforts should focus on patient engagement and access. SDM may broadly benefit patients and health care systems regardless of patient demographic/clinical characteristics.

Trends in management of ureteral urothelial carcinoma and effects on survival: a hospital-based registry study.

BACKGROUND: High-risk ureteral tumors represent an understudied subset of upper tract urothelial carcinoma, whose surgical management can range from a radical nephroureterectomy (NU) to segmental ureterectomy (SU). OBJECTIVES: To evaluate contemporary trends in the management of high-risk ureteral tumors, the utilization of lymphadenectomy and peri-operative chemotherapy, and their impact on overall survival (OS). DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective cohort study of patients in the National Cancer Database from years 2006 to 2013 with clinically localized high-risk ureteral tumors treated with NU or SU. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Chi-squared tests were utilized to assess differences in clinicodemographic features and peri-operative treatment delivery between SU and NU cohorts. Cochran-Armitage tests and linear regressions were performed to evaluate temporal trends in treatment utilization. Multivariable logistic regression models were employed to assess predictors of treatment delivery. Multivariable Cox proportional hazards models evaluated associations with OS. RESULTS: Of the 1,962 patients included, NU was more commonly performed than SU (72.4%, 1,421/1,962 vs. 27.6%, 541/1,962). Only 22.7% (446/1,962) of the population underwent lymphadenectomy, and 24.8% (271/1,092) of those with advanced pathology (≥pT2 or pN+) received adjuvant chemotherapy. Lymphadenectomy was associated with improved OS in NU patients when more than 3 nodes were removed (hazard ratio [HR] 0.58, 95% confidence interval [CI] 0.39-0.89). Receipt of adjuvant chemotherapy for advanced pathology had no impact OS in both the NU (HR 1.10, 95% CI 0.84-1.44) and SU (HR 0.94, 95% CI 0.61-1.46) cohorts. Performance of SU was not associated with poorer OS on multivariable analysis (HR 1.02, 95% CI 0.89-1.21, P = 0.83). CONCLUSION: Our study suggests that SU may be an appropriate alternative to NU for the management of high-risk ureteral tumors. Further, lymphadenectomy may play an important role at the time of NU, and adjuvant chemotherapy is infrequently utilized in patients with advanced pathology.

Analysis of guideline recommended use of renal mass biopsy and association with treatment.

INTRODUCTION: Renal mass biopsy (RMB) may not be indicated when the results are unlikely to impact management, such as in young and/or healthy patients and in elderly and/or frail patients. We analyzed the utility of RMB in three patient cohorts stratified by age-adjusted Charlson comorbidity index score (ACCI). MATERIALS AND METHODS: We identified patients with cT1a renal tumors in the National Cancer Database from 2004-2014. We combined age and Charlson-Deyo scores to identify young and/or healthy patients ('healthy-ACCI'), elderly and/or frail patients ('frail-ACCI'), and a reference cohort. We performed multivariable logistic regression to identify predictors of RMB and treatment. We evaluated the impact of RMB on management by analyzing the proportion of high-grade disease on final pathology as a surrogate for risk stratification. RESULTS: We identified 36,720 healthy-ACCI, 2,516 frail-ACCI, and 18,989 reference-ACCI patients. Healthy-ACCI patients were less likely to undergo RMB (7.5% versus 10.8%; p < 0.001) while frail-ACCI patients underwent RMB at similar rates (11.8% versus 10.8%; p = 0.14) compared with reference-ACCI patients. On multivariable logistic regression, in both healthy-ACCI and frail-ACCI patients, RMB was associated with decreased odds of surgical treatment, and increased odds of ablation and surveillance (all p < 0.01). In the frail-ACCI patients, higher grade disease at surgery was identified in the RMB cohort (32.9% versus 23.5%, p = 0.05). CONCLUSIONS: RMB is performed less frequently in healthy-ACCI patients compared with the reference cohort. RMB is associated with decreased odds of surgical treatment and increased odds of surveillance and ablation in all cohorts. In frail-ACCI patients who underwent surgery, RMB may provide additional risk stratification as these patients had lower rates of low-grade disease.

Trends in palliative care interventions among patients with advanced bladder, prostate, or kidney cancer: A retrospective cohort study.

BACKGROUND: Palliative care has an established role in improving the quality of life in patients with advanced cancer, but little is known regarding its delivery among patients with urologic malignancies. OBJECTIVE: To determine trends in the utilization of palliative interventions among patients with advanced bladder, prostate, and kidney cancer. DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective cohort study of patients from years 2004 to 2013 in the National Cancer Database diagnosed with stage IV bladder (n = 17,997), prostate (n = 23,322), and kidney (n = 34,697) cancer, after excluding those with missing disease stage, treatment, and outcomes data. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Descriptive statistics and logistic regression were performed to evaluate utilization of palliative care intervention. Utilization was analyzed by cancer type and by overall survival strata (<6, 6-24, and >24 months). Kaplan-Meier and Cox proportional hazards models analyzed overall survival. RESULTS AND LIMITATIONS: Palliative interventions were utilized in 12.5% (2,257/17,997), 14.7% (3,442/23,322), and 19.9% (6,935/34,697) of advanced bladder, prostate, and kidney cancer patients, respectively. Older age and longer survival were associated with lower odds of palliative intervention utilization in each malignancy, as was minority race in kidney and bladder cancer patients. Palliative radiation was used most commonly, and utilization of any palliative intervention was associated with poorer overall survival. Limitations largely stem from imperfect data abstraction, and the analysis of interventions' incomplete reflection of palliative care. CONCLUSIONS: Palliative interventions were seldom used among patients with advanced urologic malignancies. Palliative interventions were less frequently used in older patients and minority races. Further study is warranted to define the role of palliative interventions in advanced urologic malignancies and guide their utilization.

Predictors of adequate lymph node dissection in patients with non-muscle invasive bladder cancer undergoing radical cystectomy and effect on survival.

INTRODUCTION: Radical cystectomy (RC) is the standard of care for refractory high-risk non-muscle invasive bladder cancer (NMIBC). We aim to identify predictors of adequate lymph node dissection (LND) in a cohort of NMIBC patients undergoing RC, as well as its impact on clinical outcomes. METHODS: The National Cancer Database was queried for patients who underwent RC for urothelial cell carcinoma for clinical stage Tis/a/1 N0M0 disease between 2004 and 2013. Patients were stratified by LND: none, inadequate (<10) or adequate (≥10 nodes). Factors associated with LND were analyzed. Inverse-probability weighted propensity score matching was used to assess the impact of adequate LND on overall survival. RESULTS: The final cohort of 3,226 patients had a median follow-up of 39.0 months, had a mean age of 65.3 years, was 70% male, and was 81% Caucasian. Overall, 16.6% received no LND, 28.5% inadequate LND, and 55.0% adequate LND. Treatment at an academic facility, Charlson-Deyo Comorbidity score of 1, and later year of treatment were significantly associated with adequate LND. Overall survival was significantly higher with adequate LND compared to a matched-cohort of inadequate LND patients (68.7% vs. 60.6% at 5 years, P < 0.01). CONCLUSIONS: Nearly half of NMIBC patients undergoing RC do not receive an adequate LND, despite an association with increased overall survival. Treatment at an academic facility was associated with increased likelihood of adequate LND. Initiatives to improve adequate LND in this population may be warranted.

Positive surgical margins at radical prostatectomy in the United States: Institutional variations and predictive factors.

INTRODUCTION: Positive surgical margins (PSMs) are associated with treatment failure after radical prostatectomy (RP) for patients with prostate cancer (CaP). We investigated institutional variations in PSM after RP, as well as clinical and demographic factors predicting PSM. PATIENTS AND METHODS: Patients undergoing RP for clinically localized CaP were identified in the National Cancer Database in 2010 to 2013 and clinicodemographics were recorded. Treating institution was defined as academic (AMC) or nonacademic medical centers (nAMC). The primary outcome was the PSM rate. Multivariable logistic regression and propensity matching with inverse probability treatment weighing were used to both compare outcomes between AMC and nAMC and to identify predictors of PSM following RP. RESULTS: A total of 167,260 patients met our inclusion criteria. PSM rate was significantly lower in patients treated at AMC (13,435, 18.9%) compared with 22,145 (23.0%) in those treated at nAMC (P < 0.01). The difference between PSM rate in AMC and nAMC was more pronounced in lower volume centers while it was not significant in higher volume centers. On multivariable analysis, age, race, prostate-specific antigen (PSA), biopsy Gleason score, comorbidity profile, insurance type, income, and treatment facility were significantly associated with PSM rate. CONCLUSION: PSM rates appear to be lower at AMC and higher volume facilities, which can potentially reflect institutional differences in surgical quality. In addition, we identified several socioeconomic and demographic factors that contribute to the likelihood of PSM following RP for localized CaP, suggesting potential systematic variation in the quality of surgical care. The cause of this variation warrants further investigation and evaluation.

Repair of iatrogenic ureteral injury secondary to breast cancer metastasis.

We present a case of unforeseen ureteral metastasis from a primary breast cancer. A ureteral injury leak was postoperatively recognized after a hysterectomy and bilateral oophorectomy were performed. Subsequent repair with a psoas hitch ureteral re-implant was performed and breast cancer metastasis was discovered in the ureteral stump specimen.

Cytoreductive nephrectomy in patients with metastatic renal cell carcinoma and venous thrombus-Trends and effect on overall survival.

PURPOSE: Patients with metastatic renal cell carcinoma (mRCC) commonly present with tumor thrombi in the renal vein and inferior vena cava (IVC). The benefit of cytoreductive nephrectomy (CN) in this population is unclear and the effect on overall survival (OS) has been incompletely evaluated. MATERIALS AND METHODS: We queried the National Cancer Database from 2010 to 2013 for patients diagnosed with mRCC and tumor thrombi, which was defined as renal vein, infradiaphragmatic IVC, or supradiaphragmatic IVC. Descriptive statistics were performed and associations between clinicopathologic variables and utilization of CN were analyzed. Patients were matched on the receipt of CN and Kaplan-Meier analyses and multivariable Cox proportional hazards models were used to estimate survival. RESULTS: In total, 8,629 patients were found to have mRCC during the study period. Approximately 27% (n = 2,376) had tumor thrombus. Tumor thrombus was associated with increased rates of CN utilization, however rates decreased as thrombus level increased. In a matched Kaplan-Meier analysis, CN was associated with improved OS in patients without thrombus, and with renal vein or infradiaphragmatic thrombus (all P < 0.01). Patients with supradiaphragmatic thrombus did not benefit from CN (P = 0.46). This effect was confirmed in a Cox proportional hazards model. CONCLUSIONS: Tumor thrombus is common in patients with mRCC. OS is poor, and patient and tumor specific factors influence the use of CN. Despite discrepancies in utilization, CN is associated with improved OS, although this effect appears to be limited to those with mRCC and tumor thrombus limited to the renal vein and infradiaphragmatic IVC.

Treatment utilization and overall survival in patients receiving radical nephroureterectomy versus endoscopic management for upper tract urothelial carcinoma: evaluation of updated treatment guidelines.

PURPOSE: While radical nephroureterectomy (RNU) is the gold standard treatment for upper tract urothelial carcinoma (UTUC), select patients may benefit from endoscopic treatment (ET). European Association of Urology guidelines recommend ET for patients with low-risk (LR) disease: unifocal, < 2 cm, low-grade lesions without local invasion. To inform the utility of ET, we compare the overall survival (OS) of patients receiving ET and RNU using current and previous guidelines of LR disease. MATERIALS AND METHODS: Patients with non-metastatic, cT1 or less UTUC diagnosed in 2004-2012 were collected from the National Cancer Database. OS was analyzed with inverse probability of treatment weighted Cox proportional hazard regression. Analyses were conducted for LR disease under updated (size < 2 cm) and previous guidelines (size < 1 cm). RESULTS: Patients who were older, healthier, and treated at an academic facility had higher odds of receiving ET. In 851 identified patients with LR disease, RNU was associated with increased OS compared with ET (p = 0.006); however, there was no difference between ET and RNU (p = 0.79, n = 202) under the previous guidelines (size < 1 cm). In, otherwise, LR patients, the largest tumor size with no difference between ET and RNU was ≤ 1.5 cm (p = 0.07). CONCLUSIONS: RNU is associated with improved survival when compared with ET in the management of LR UTUC using current guidelines with a size threshold of < 2 cm. In appropriately selected LR patients, we find no difference between RNU and ET up to a tumor size of ≤ 1.5 cm. However, in the absence of prospective studies, the usage of ET is best left up to clinician discretion.

Variation in surgical treatment patterns for patients with prostate cancer in the United States: Do patients in academic hospitals fare better?

INTRODUCTION: With prostate cancer (CaP) screening, overtreatment of low-risk CaP remains a concern. We investigated the patterns of radical prostatectomy (RP) for pathologic insignificant (iCaP) and significant CaP (sCaP) as well as variations between academic and nonacademic hospitals. PATIENTS AND METHODS: Patients undergoing RP for clinical T1c CaP were identified in the National Cancer Database between 2006 and 2013. The primary outcome was the trend of RP for insignificant prostate cancer (iCaP) and significant prostate cancer (sCaP) over the study period. The secondary outcome was to compare the RP rate in academic vs. nonacademic institutions. Univariable and multivariable analysis were utilized to evaluate the association between overtreatment and practice type. iCaP was defined as organ confined CaP with Gleason Score ≤6. RESULTS: The total number of RP increased from 17,970 cases in 2006 to 25,324 in 2013. The RP rate decreased for iCaP from 39.9% to 19.8%, while increasing for sCaP from 18% to 27% over the study period. Patients undergoing RP in academic settings were less likely to have iCaP (odds ratio 0.88, 95% confidence interval 0.80-0.97). Caucasian race, private insurance, younger age, and treatment in the Eastern United States were associated with higher rates of iCaP at RP. CONCLUSION: The rate of iCaP has declined over time in the United States for patients undergoing RP. Although RP in nonacademic setting was more likely to have iCaP on surgical pathology, this trend has been downward among practice types. Treatment appropriateness is an underrecognized, undermeasured, but increasingly important component of the high-value care discussion that warrants greater attention.

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.

Overall survival in patients with residual disease after radical cystectomy and neoadjuvant chemotherapy.

BACKGROUND: Neoadjuvant chemotherapy (NAC) has been shown to improve survival in patients with urothelial carcinoma (UC). However, there are a subset of patients who do not respond or progress despite systemic treatment. METHODS: Data from the National Cancer Database on patients who underwent a radical cystectomy (RC) with or without NAC from 2006 to 2013 were abstracted. Covariates were balanced using inverse probability weighting methods. The primary outcome of overall survival in patients with residual disease by stage was evaluated using 90-day conditional landmark analysis and Cox proportional hazards modeling. Secondary outcome of predictors of residual disease was evaluated using multivariable logistic regression analysis. RESULTS: A total of 20,128 patients met our inclusion criteria; 16,058 patients underwent RC only (80%) and 4070 underwent RC with NAC (20%). Patients who received NAC were younger and healthier, treated at an academic center, and presented with higher stage. NAC was associated with improved overall survival amongst patients with cT3-4aN0 (HR 0.84 95% CI 0.73-0.97; p = 0.02) and cN+ (HR 0.70, 95% CI 0.58-0.86; p = 0.001). Predictors of no residual disease were NAC (OR 0.17, 95% CI 0.14-0.21; p < 0.001) and treatment at an academic facility (OR 0.47, 95% CI 0.37-0.60; p < 0.001). Patients with cT3-4a or cN+ had increased odds of having residual UC (OR 2.01, 95% CI 1.53-2.64; p < 0.001, and OR 2.14, 95% CI 1.43-3.21; p < 0.001, respectively) compared with cT2. CONCLUSION: In patients with residual UC, NAC is associated with a significant survival benefit in higher stage disease only. Furthermore, those treated with NAC or at an academic center were less likely to have residual disease. Given the toxicity of NAC, more prudent patient selection for NAC is warranted and requires further study.

Trends in usage of cytoreductive partial nephrectomy and effect on overall survival in patients with metastatic renal cell carcinoma.

PURPOSE: Cytoreductive radical nephrectomy (cRN) improves survival in select patients with metastatic renal cell carcinoma (mRCC). It is unclear, however, whether cytoreductive partial nephrectomy (cPN) compromises oncologic efficacy. We evaluated trends in utilization of cPN and compared overall survival (OS) in patients who underwent cRN or cPN for mRCC. MATERIALS AND METHODS: We queried the National Cancer Database from 2006 to 2013 and identified patients who underwent cPN and cRN for mRCC. We analyzed rates of cPN over time. Logistic regression identified predictors of cPN. We matched patients based on propensity score for treatment. We used matched Kaplan-Meier survival analyses to compare OS, stratified by tumor size. We used multivariable Cox proportional hazards models to determine the effect of cPN and cRN on OS. RESULTS: A total of 10,144 patients met inclusion criteria, with 9,764 (96.2%) undergoing cRN and 381 (3.8%) undergoing cPN. Rates of cPN increased over time from 1.8% to 4.3% over the study period. Treatment at an academic/research facility, papillary and chromophobe histology, and more recent year of treatment were associated with increased odds of cPN. In a matched survival analysis, cPN was associated with improved OS compared with cRN (log rank, P = 0.001). This effect was limited to primary tumors<4cm. In a propensity-score adjusted multivariable Cox model, cPN was associated with improved OS (hazard ratio = 0.81; 95% CI: 0.71-0.93; P = 0.002). CONCLUSIONS: The use of cPN in patients with mRCC is increasing. cPN is associated with improved OS in patients with mRCC, although this effect is limited to patients with primary tumors<4cm.

Role of surgical approach on lymph node dissection yield and survival in patients with upper tract urothelial carcinoma.

OBJECTIVES: With increasing utilization of robot-assisted surgery in urologic oncology, robotic nephroureterectomy (RNU) is becoming the surgical modality of choice for patients with upper tract urothelial carcinoma (UTUC). The role of surgical approach on lymph node dissection (LND) and lymph node (LN) yield is unclear, and potential therapeutic effects are unknown. Here we analyze the effects of surgical approach on LN yield, performance of LND, and overall survival (OS). METHODS AND MATERIALS: Patients with UTUC who underwent nephroureterectomy from 2010 to 2013 were identified in the National Cancer Database. Outcomes of interest included rate of LND, LN yield, and OS. Logistic regression analyses were used to predict performance of LND. Negative binomial regression was used to derive incidence rate ratios for LN yield. Cox proportional hazards models were used to quantify survival outcomes. RESULTS: A total of 3,116 patients met inclusion criteria. LND was performed in 41% (314/762) of RNU, 27% (380/1385) of LNU cases, and 35% (340/969) of ONU (P<0.001). Compared with an ONU, patients who underwent a LNU had significantly lower odds of receiving a LND (OR = 0.70, 95% CI: 0.55-0.87) and had fewer LNs removed (IRR = 0.69, 95% CI: 0.60-0.80), while RNU trended toward increased LN yield (IRR = 1.14, 95% CI: 0.98-1.33). In a Cox proportional hazards model, increasing LN yield was associated with improved OS in patients with pN0 disease (HR = 0.97 per 1 unit increase in LN yield, 95% CI: 0.95-0.99). CONCLUSIONS: Compared with an ONU, RNU does not compromise performance of a LND and may be associated with improved LN yield. LNU is associated with the lowest rates of LND and LN yield. Increasing LN yield is associated with improved OS in patients with pN0 disease. Despite differential rates of LND and LN yield, surgical approach did not independently affect OS.

Phase II prospective randomized trial of weight loss prior to radical prostatectomy.

BACKGROUND: Obesity 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. METHODS: In 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. RESULTS: In 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. CONCLUSIONS: In 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.

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.

Association between tumor-associated macrophage infiltration, high grade prostate cancer, and biochemical recurrence after radical prostatectomy.

BACKGROUND: Tumor-associated macrophages (TAMs) are a key component of the inflammatory microenvironment. Their role in prostate cancer development and progression remains unclear. We examined whether the amount of TAMs in prostate cancer is: 1) higher than prostatic intraepithelial neoplasia (PIN) and benign tissue 2) associated with poorly differentiated disease, and 3) predictive of biochemical recurrence among surgically treated men. METHODS: A tissue microarray (TMA) of prostatectomy specimens from 332 patients was stained for CD68, a TAM marker. A separate TMA was used for validation. Associations between mean TAMs in cancer cores and PSA recurrence were determined by Cox proportional hazards models after adjusting for age, preoperative PSA, race, body mass index, pathologic Gleason sum, seminal vesicle invasion, extracapsular extension, and margin status. RESULTS: Mean TAM number was higher in cancer versus PIN and benign tissue (p<0.0001). Mean TAM number was higher in Gleason grade 4 cores vs. Gleason grade 3 cores (p=0.003). On multivariable analysis, no association was observed between mean TAM number per cancer core and biochemical recurrence in either cohort. CONCLUSION: Mean TAM number was higher in cancer cores vs. PIN and benign tissue, and higher in high grade prostate cancer supporting the potential role of TAMs in prostate cancer development. However, TAMs were not associated with biochemical recurrence after radical prostatectomy suggesting TAM counts do not provide independent prognostic value among surgically treated men. Further studies are required to elucidate the functional significance of TAMs in the prostate cancer microenvironment.

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.

Human palatine tonsil: a new potential tissue source of multipotent mesenchymal progenitor cells.

INTRODUCTION: Mesenchymal progenitor cells (MPCs) are multipotent progenitor cells in adult tissues, for example, bone marrow (BM). Current challenges of clinical application of BM-derived MPCs include donor site morbidity and pain as well as low cell yields associated with an age-related decrease in cell number and differentiation potential, underscoring the need to identify alternative sources of MPCs. Recently, MPC sources have diversified; examples include adipose, placenta, umbilicus, trabecular bone, cartilage, and synovial tissue. In the present work, we report the presence of MPCs in human tonsillar tissue. METHODS: We performed comparative and quantitative analyses of BM-MPCs with a subpopulation of adherent cells isolated from this lymphoid tissue, termed tonsil-derived MPCs (T-MPCs). The expression of surface markers was assessed by fluorescent-activated cell sorting analysis. Differentiation potential of T-MPCs was analyzed histochemically and by reverse transcription-polymerase chain reaction for the expression of lineage-related marker genes. The immunosuppressive properties of MPCs were determined in vitro in mixed lymphocyte reactions. RESULTS: Surface epitope analysis revealed that T-MPCs were negative for CD14, CD31, CD34, and CD45 expression and positive for CD29, CD44, CD90, and CD105 expression, a characteristic phenotype of BM-MPCs. Similar to BM-MPCs, T-MPCs could be induced to undergo adipogenic differentiation and, to a lesser extent, osteogenic and chondrogenic differentiation. T-MPCs did not express class II major histocompatibility (MHC) antigens, and in a similar but less pronounced manner compared with BM-MPCs, T-MPCs were immunosuppressive, inhibiting the proliferation of T cells stimulated by allogeneic T cells or by non-specific mitogenic stimuli via an indoleamine 2,3-dioxygenase-dependent mechanism. CONCLUSION: Human palatine T-MPCs represent a new source of progenitor cells, potentially applicable for cell-based therapies.