Access to prior spatial information.

In six experiments, reading times and probe naming times were measured in order to examine the conditions under which spatial information became accessible and/or reactivated. In Experiments 1-4, reading times were measured for target sentences containing spatial inconsistencies. Spatial inconsistencies did not disrupt processing (Experiment 1) unless there were increases in task demands (Experiment 2), elaboration of the protagonist's location (Experiment 3), or both (Experiment 4). In Experiments 5 and 6, naming times were measured to directly assess the activation of spatial information, specifically objects associated with a protagonist. Spatial information was highly active in memory immediately after being read and less active after four intervening sentences (Experiment 5), but explicit cues (e.g., location or object) as well as references to the current situation model were effective in reactivating previously mentioned spatial information (Experiment 6). The combined results of six experiments are discussed within the context of the RI-Val model.

Patient-Reported Sexual Survivorship Following High-Dose Image-Guided Proton Therapy for Prostate Cancer.

OBJECTIVE: To help guide individualized treatment, we sought to identify baseline predictive factors that impact long-term erectile function following high-dose image-guided radiotherapy (HD-IGRT). METHODS: Potent men with localized prostate cancer treated with radiotherapy alone were enrolled in an institutional review board-approved prospective cohort study. Men received HD-IGRT as primary treatment of prostate cancer. Patient-reported inventories were used to assess erectile function at baseline, 6 months, 2 years, and 5 years after treatment. Long-term potency rates were compared to validated models, and baseline factors were used to create a novel, internally validated nomogram for predicting long-term function. RESULTS: 1,159 men were treated with HD-IGRT. Among 676 men who were potent at baseline and did not receive hormone therapy, the potency rates at 6 months, 2 years, and 5 years were 81%, 68%, and 61%. Recursive partitioning categorized patients into 3 groups based on two factors: baseline response to EPIC Q57 (ability to have an erection) and pre-existing heart disease. At 5 years, the most favorable group reported "very good" on Q57 and had an 80% potency rate (n = 137; p = 0.83); the intermediate group reported "good" on Q57 and had no baseline cardiac disease with a 62% potency rate (n = 145; p = 0.86); and the remaining poor risk group had a 37% potency rate (n = 117; p = 0.19). CONCLUSIONS: Patient-reported pretreatment sexual function and comorbidities enables stratification and prediction of erectile function. EPIC subset questions with baseline comorbidities may potentially serve as a quick and practical clinical tool for predicting sexual survivorship.

Serum Testosterone 60 Months after Passive-Scatter Proton Therapy for Localized Prostate Cancer.

Studies demonstrate a decline of ∼10% in serum testosterone (ST) level after X-ray radiotherapy for prostate cancer. We evaluated changes in ST for patients with low- and intermediate-risk prostate cancer receiving 70-82Gy(RBE) using passive-scatter proton therapy (PT). ST was checked at baseline (n = 358) and at 60+ months after PT (n = 166). The median baseline ST was 363.3 ng/dl (range, 82.0-974.0). The median ST 5 years after PT was 391.5 ng/dl (range, 108.0-1061.0). The difference was not statistically significant (p = 0.9341). Passive-scatter PT was not associated with testosterone suppression at 5 years, suggesting that protons may cause less out-of-field scatter radiation than X-rays.

Optimal medical management before lower extremity bypass for claudication in the veteran population.

OBJECTIVE: Optimizing medical management through glucose control, smoking cessation, and drug therapy (ie, antiplatelet and statin agents) is recommended as first-line therapy for patients with claudication. The aims of this study were to determine how frequently veterans with claudication received optimal medical management (OMM) before undergoing elective open lower extremity bypass procedures nationwide and whether preoperative OMM was associated with improved surgical outcomes. METHODS: We reviewed all patients within the Veterans Affairs (VA) Surgical Quality Improvement Program database who underwent elective open lower extremity bypass procedures for claudication at nationwide VA medical centers from 2005 until 2015. We defined OMM as a claudicant's having documentation of receiving all of the following within 12 months before surgery: prescriptions for antiplatelet, statin, and smoking cessation therapy (if a smoker) and monitoring of hemoglobin A1c (if diabetic). Outcome measures included occurrence of any 30-day VA Surgical Quality Improvement Program complication, amputation-free survival, and 30-day and 1-year mortality. We used multivariate regression and Cox proportional hazards models incorporating inverse probability treatment weighting to analyze the effect of OMM on outcome measures after adjusting for patient-level confounding. RESULTS: Among 10,271 lower extremity bypass procedures performed, 2265 (22%) were undertaken in claudicants with a median age of 63 years (interquartile range, 58-68 years). Of claudicants, 839 (37%) were diabetic, and 1333 (59%) patients smoked within 12 months before surgery. OMM was achieved in only 581 (26%) claudicants before they underwent surgery, although adherence to individual components was variable: antiplatelet, 55%; statin, 63%; smoking cessation, 58%; and hemoglobin A1c monitoring, 92%. In risk-adjusted analyses, there were no statistically significant differences in complication rates, amputation-free survival, or mortality outcomes among patients who received OMM compared with non-OMM patients. CONCLUSIONS: Only a quarter of veterans with claudication were documented as receiving OMM within the year before undergoing open lower extremity bypass across nationwide VA medical centers, highlighting the need for strategies to ensure that medical therapy is intensified before surgical revascularization. Nevertheless, our data showed that documentation of preoperative OMM did not lead to improved short- or long-term postoperative outcomes in these patients, suggesting that more objective measures of medical management are needed to ensure that peripheral arterial disease goals are achieved.

Rectal Culture and Sensitivity Analysis for Reducing Sepsis Risk After Fiducial Marker Placement.

PURPOSE: Placement of fiducial markers for prostate radiotherapy (RT) is associated with a 2% to 3% risk of bacterial urinary tract infection (UTI) that may progress to sepsis necessitating hospitalization. These bacterial UTIs are primarily due to flouroquinolone (FQ) resistant Escherichia coli (E. coli). The incidence of this complication has increased in recent years. The purpose of this study is to determine whether rectal culture and sensitivity (C&S) to identify FQ resistant E. coli obtained before placement of fiducial markers for prostate RT reduces the likelihood of this complication. METHODS: In total, 412 patients treated with RT at the University of Florida Proton Therapy Institute between 2015 and 2017 were included in the study. Rectal C&S were obtained at the time of initial consultation which preceded placement of fiducial markers for planning and realignment for prostate RT. Patients in whom resistant E. coli were identified had their prophylactic antibiotic regimen modified accordingly. Whether bacterial UTI requiring hospitalization following fiducial placement occurred was prospectively recorded in the medical record on the first day of RT. RESULTS: One of 412 patients (0.2%) developed bacterial sepsis requiring hospitalization after fiducial placement. CONCLUSION: Rectal C&S to identify FQ resistant E. coli before placement of fiducial markers for prostate RT likely reduces the risk of bacterial UTI necessitating hospitalization.

Validating semantic illusions: Competition between context and general world knowledge.

The RI-Val model of comprehension includes a validation process in which linkages formed by integration are matched against active memory. In five experiments, we investigated factors that influence validation. Reading times were measured on target sentences that contained either correct information or semantically related, but incorrect content. Experiment 1 demonstrated that strong contextual support for shared features between correct and incorrect terms delayed processing difficulty associated with incorrect information. Experiment 2 confirmed that contextual information needed to be available in memory in order to influence validation. Experiments 3a and 3b showed that strong contextual support for distinguishing features between correct and incorrect terms led to immediate processing difficulty associated with incorrect information, whereas features-in-common led to delayed difficulty. Experiments 4 and 5 showed that the timing of validation effects is sensitive to subtle changes in task demands. The combined results are consistent with the assumptions of the RI-Val model. (PsycINFO Database Record

Long-term supplementation of decaffeinated green tea extract does not modify body weight or abdominal obesity in a randomized trial of men at high risk for prostate cancer.

BACKGROUND: Evidence continues to demonstrate the role of obesity in prostate carcinogenesis and prognosis, underscoring the need to identify and continue to evaluate the effective interventions to reduce obesity in populations at high risk. The aim of the study was to determine the effect of daily consumption of decaffeinated green tea catechins (GTC) formulation (Polyphenon E® (PolyE)) for 1 year on biomarkers of obesity in men who are at high risk for prostate cancer. MATERIALS AND METHODS: A randomized, double-blinded trial was conducted targeting 97 men diagnosed with HGPIN or ASAP. Subjects were randomized to receive GTC (PolyE) (n = 49) or placebo (n = 48) for 1 year. Anthropometric data were collected at baseline, 6 and 12 months and data analyzed to observe change in weight, body mass index (indicator of obesity) and waist: hip ratio (indicator of abdominal obesity). RESULTS: Decaffeinated GTC containing 400 mgs of the bioactive catechin, EGCG administered for 1 year to men diagnosed with ASAP and HGPIN appears to be bioavailable, well tolerated but not effective in reducing biomarkers of obesity including body weight, body mass index and waist: hip ratio. CONCLUSIONS: The results of our trial demonstrates that men who are obese and at high risk for prostate cancer should resort to effective weight management strategies to reduce obesity and not resort to ineffective measures such as taking supplements of green tea to reduce biomarkers of obesity. Changes in body mass index and abdominal obesity seen in other studies were potentially due to caffeine and not GTC.

Effectiveness of open versus endovascular abdominal aortic aneurysm repair in population settings: A systematic review of statewide databases.

BACKGROUND: Patient outcomes after open abdominal aortic aneurysm and endovascular aortic aneurysm repair have been widely reported from several large, randomized, controlled trials. It is not clear whether these trial outcomes are representative of abdominal aortic aneurysm repair procedures performed in real-world hospital settings across the United States. This study was designed to evaluate population-based outcomes after endovascular aortic aneurysm repair versus open abdominal aortic aneurysm repair using statewide inpatient databases and examine how they have helped improve our understanding of abdominal aortic aneurysm repair. METHODS: A systematic search of MEDLINE, EMBASE, and CINAHL databases was performed to identify articles comparing endovascular aortic aneurysm repair and open abdominal aortic aneurysm repair using data from statewide inpatient databases. This search was limited to studies published in the English language after 1990, and abstracts were screened and abstracted by 2 authors. RESULTS: Our search yielded 17 studies published between 2004 and 2016 that used data from 29 different statewide inpatient databases to compare endovascular aortic aneurysm repair versus open abdominal aortic aneurysm repair. These studies support the randomized, controlled trial results, including a lower mortality associated with endovascular aortic aneurysm repair extended from the perioperative period up to 3 years after operation, as well as a higher complication rate after endovascular aortic aneurysm repair. The evidence from statewide inpatient database analyses has also elucidated trends in procedure volume, patient case mix, volume-outcome relationships, and health care disparities associated with endovascular aortic aneurysm repair versus open abdominal aortic aneurysm repair. CONCLUSION: Population analyses of endovascular aortic aneurysm repair and open abdominal aortic aneurysm repair using statewide inpatient databases have confirmed short- and long-term mortality outcomes obtained from large, randomized, controlled trials. Moreover, these analyses have allowed us to assess the effect of endovascular aortic aneurysm repair adoption on population outcomes and patient case mix over time.

Race Does Not Affect Tumor Control, Adverse Effects, or Quality of Life after Proton Therapy.

PURPOSE: To compare 5-year biochemical control, toxicity, and patient-reported quality of life (QOL) outcomes for African American and White patients treated with proton therapy (PT) for prostate cancer. MATERIALS AND METHODS: We reviewed the medical records of 1,066 men with clinically localized prostate cancer. Patients were treated with definitive PT between 2006 and 2010. Patients received a median radiation dose of 78 Gy (RBE) with conventional fractionation (1.8- 2 Gy [RBE] per fraction). Sixty-eight (6.4%) men self-identified as African American and 998 (93.6%) self-identified as White. Five-year rates of biochemical control, grade 3 genitourinary and gastrointestinal toxicity, and patient-reported QOL are reported and compared between African American and White patients. RESULTS: Median biochemical follow-up was 5.0 years for both African American and White patients. Median follow-up for toxicity was 5.0 and 5.2 years, respectively. On multivariate analysis, race was not a significant predictor for 5-year freedom from biochemical failure (HR 0.8, p=0.55). No significant association was found between race and grade 3 genitourinary toxicity on multivariate analysis at 5 years (HR 2.5, p=0.10). Patient-reported QOL using median EPIC bowel, urinary incontinence, and irritative summaries scores were not significantly different between the groups. African Americans had higher median sexual summary scores at 2 years than White patients (75 vs. 54, p=0.01) but by 5+ years, the sexual summary scores were no longer significantly different (63 vs. 53, p=0.35). CONCLUSION: With a median follow-up of 5 years, there were no racial disparities in biochemical control, grade 3 toxicity, or patient-reported QOL after PT for prostate cancer.

Five-Year Biochemical Results, Toxicity, and Patient-Reported Quality of Life After Delivery of Dose-Escalated Image Guided Proton Therapy for Prostate Cancer.

PURPOSE: To report clinical outcomes in patients treated with image guided proton therapy (PT) for localized prostate cancer. METHODS AND MATERIALS: The medical records of 1327 men were reviewed. Each man was enrolled on an outcomes tracking study. Dual enrollment on a prospective clinical trial was allowed. Each patient was treated for localized prostate cancer with PT at our institution between 2006 and 2010. Ninety-eight percent of patients received 78 Gy (radiobiological equivalent [RBE]) or higher; 18% received androgen deprivation therapy (ADT). The 5-year freedom from biochemical progression (FFBP), distant metastasis-free survival, and cause-specific survival rates are reported for each risk group. Data on patient-reported quality of life and high-grade toxicities were prospectively collected and reported. A multivariate analysis was performed to identify clinical predictors of biochemical failure and urologic toxicity. RESULTS: The median follow-up time was 5.5 years. The 5-year FFBP rates were 99%, 94%, and 74% in low-risk, intermediate-risk, and high-risk patients, respectively. The actuarial 5-year rates of late grade 3+ Common Terminology Criteria for Adverse Events, version 4.0, gastrointestinal (GI) and genitourinary (GU) toxicity were 0.6% and 2.9%, respectively. Multivariate analysis showed a significant correlation between grade 3+ GU toxicity and pretreatment prostate reductive procedures (P<.0001), prostate volume (P=.0085), pretreatment α-blockers (P=.0067), diabetes (P=.0195), and dose-volume histogram parameters (P=.0208). The median International Prostate Symptom Scores pretreatment scores and scores at 5 years after treatment were 7 and 7, respectively. The mean Expanded Prostate Cancer Index Composite (EPIC) scores significantly declined for sexual summary for patients not receiving ADT (from 67 to 53) between baseline and 5 years. CONCLUSIONS: Image guided PT provided excellent biochemical control rates for patients with localized prostate cancer. The actuarial rates of high-grade toxicity were low after PT. From pretreatment to 5 years of follow-up, a significant decline was found only in mean EPIC sexual summary scores. Prospective clinical studies are needed to determine the comparative effectiveness of PT and other radiation treatment strategies.

Proton Therapy as Salvage Treatment for Local Relapse of Prostate Cancer Following Cryosurgery or High-Intensity Focused Ultrasound.

PURPOSE: Local recurrence of prostate cancer after cryosurgery (CS) and high-intensity focused ultrasound (HIFU) is an emerging problem for which optimal management is unknown. Proton therapy (PT) may offer advantages over other local therapeutic options. This article reviews a single institution's experience using PT for salvage of local recurrent disease after HIFU or CS. METHODS AND MATERIALS: We reviewed the medical records of 21 consecutive patients treated with salvage PT following a local recurrence of prostate cancer after CS (n=12) or HIFU (n=9) between January 2007 and July 2014. Patients were treated to a median dose of 74 Gy(relative biological effectiveness [RBE]; range: 74-82 Gy[RBE]) and 8 patients received androgen deprivation therapy with radiation therapy. Patients were evaluated for quality of life (QOL) by using the Expanded Prostate Index Composite questionnaire and toxicity by using Common Terminology Criteria for Adverse Events, version 3.0, weekly during treatment, every 6 months for 2 years after treatment, and then annually. RESULTS: Median follow-up was 37 months (range: 6-95 months). The 3-year biochemical progression-free survival (bPFS) rate was 77%. The 3-year grade 3 toxicity rate was 17%; however, 2 of these patients had pre-existing grade 3 GU toxicities from their HIFU/CRYO prior to PT. At 1 year, bowel summary, urinary incontinence, and urinary obstructive QOL scores declined, but only the bowel QOL score at 12 months met the minimally important difference threshold. CONCLUSIONS: PT achieved a high rate of bPFS with acceptable toxicity and minimal changes in QOL scores compared with baseline pre-PT functions. Although most patients have done fairly well, the study size is small, follow-up is short, and early results suggest that outcomes with PT for salvage after HIFU or CS failure are inferior to outcomes with PT given in the de novo setting with respect to disease control, toxicity, and QOL.

The rapid identification of elution conditions for therapeutic antibodies from cation-exchange chromatography resins using high-throughput screening.

Cation-exchange chromatography is widely used in the purification of therapeutic antibodies, wherein parameters such as elution pH and counterion concentration require optimization for individual antibodies across different chromatography resins. With a growing number of antibodies in clinical trials and the pressure to expedite process development, we developed and automated a high-throughput batch-binding screen to more efficiently optimize elution conditions for cation-exchange chromatography resins. The screen maps the binding behavior of antibodies and impurities as a function of pH and counterion concentration in terms of a partition coefficient (Kp). Using this approach, the binding behavior of a library of antibodies was assessed on Poros 50HS and SP Sepharose Fast Flow resins. The diversity in binding behavior between antibodies and across resins translated to the requirement of a variable counterion concentration to elute each antibody. This requirement can be met through the use of a gradient elution. However, a gradient of increasing counterion concentration spans the transition from binding to non-binding for impurities as well as the antibody, resulting in the elution of impurities within the antibody elution peak. Step elution conditions that selectively elute the antibody while retaining impurities on the resin can now be rapidly identified using our high-throughput approach. We demonstrate that by correlating antibody Kp to elution pool volume and yield on packed-bed columns and through the calculation of a separation factor, we can efficiently optimize step elution conditions that maximize impurity clearance and yield for each antibody.

Randomized, placebo-controlled trial evaluating the safety of one-year administration of green tea catechins.

PURPOSE: Although preclinical, epidemiological and prior clinical trial data suggest that green tea catechins (GTCs) may reduce prostate cancer (PCa) risk, several preclinical studies and case reports have reported liver toxicities and acute gastrointestinal bleeding. Based on these observations, regulatory bodies have required stringent inclusion criteria with frequent, excessive toxicity monitoring and early stopping rules in clinical trials. These requirements have impeded recruitment and retention of subjects in chemoprevention trials and subsequent progress in agent development efforts. EXPERIMENTAL DESIGN: We conducted a placebo-controlled, randomized clinical trial of Polyphenon E® (PolyE®), a proprietary mixture of decaffeinated GTCs, containing 400 mg (-)-epigallocatechin-3-gallate (EGCG) per day, in 97 men with high-grade prostatic intraepithelial neoplasia (HGPIN) and/or atypical small acinar proliferation (ASAP). PolyE® containing 200 mg EGCG was administered with food, BID. A secondary study endpoint in this trial was a comparison of the overall one-year treatment related adverse events and grade 3 or higher adverse event on the two study arms. Monthly assessments of toxicity (CTCAE 4.0), concomitant medications and organ function, including hepatic panel, PT/PTT and LDH, were performed. RESULTS: Daily intake of a standardized, decaffeinated, catechin mixture containing 200 mg EGCG BID taken with food for 1 year accumulated in plasma and was well tolerated and did not produce treatment related adverse effects in men with baseline HGPIN or ASAP. CONCLUSION: The current data provides evidence of safety of decaffeinated, catechin mixture containing 200 mg EGCG BID to be further tested for prostate cancer prevention or other indications.

Patient-Reported Quality of Life in Men with Transurethral Resection of the Prostate Undergoing Proton Therapy for Management of Prostate Cancer.

PURPOSE: We report on quality of life (QOL) and early toxicity among men with prostate cancer who underwent transurethral resection of the prostate (TURP) before proton therapy. MATERIALS AND METHODS: Between 2006 and 2010, 1,289 patients were treated definitively with proton therapy for prostate cancer at our institution and enrolled on a prospective outcomes-tracking protocol. Ninety-six of the men had received a TURP before proton therapy, while 1,193 men had not. Baseline comorbidities, medications, expanded prostate index composite (EPIC) score, international prostate symptom score (IPSS), and CTCAE vs.3 toxicity assessment were collected prospectively. The Kaplan-Meier product limit method was used to estimate freedom from toxicity. RESULTS: Men who had TURP before proton therapy had lower baseline EPIC scores for urinary incontinence, bowel summary, and sexual summary compared with the non-TURP group, but no significant difference in urinary obstructive score was observed. After controlling for baseline scores, there was no significant difference in bowel summary or sexual summary scores between the two groups over time. There were, however, differences for urinary irritation/obstruction scores and urinary incontinence scores favoring those patients who did not have a TURP-like procedure. Toxicity assessment showed that the 2-year and 5-year rates of grade 3 genitourinary toxicity in the pretreatment TURP group were 12.3% and 17.2%, respectively. CONCLUSIONS: Pretreatment TURP was associated with both a high incidence of physician-assessed toxicity and inferior patient-reported QOL scores both before and after proton therapy treatment. Studies investigating QOL and toxicity after specific prostate cancer therapies should stratify patients by pretreatment TURP. Longer follow-up is needed to confirm if these differences ever resolve.

Bacterial Urinary Tract Infection after Transrectal Placement of Fiducial Markers prior to Proton Radiotherapy for Prostate Cancer.

PURPOSE: To determine the incidence of a bacterial urinary tract infection (UTI) necessitating hospitalization after transrectal placement of fiducial markers prior to proton radiotherapy (RT) for prostate cancer. MATERIALS AND METHODS: Six hundred sixty six patients returning for follow up after proton RT consented to participate in this institutional review board (IRB) approved study. Patients were queried whether they required hospitalization within 1 month of transrectal placement of fiducial markers. Patients were treated with proton RT between August 2006 and December 2014. Median International Prostate Symptom Score (IPSS) was 7. Sixty four patients (9.6%) had diabetes, 9 patients (1.4%) had chronic obstructive pulmonary disease, 6 patients (0.9%) had prior bladder surgery, 7 patients (1.1%) had a transurethral prostatectomy within 3 months, and 549 patients (82.4%) had a course of antibiotics within 6 months. Fifty five patients (8.3%) were taking tamsulosin, 16 patients (2.4%) were taking finasteride, and 62 patients (9.3%) were taking saw palmetto. The interval between the most recent prostate biopsy prior to fiducial placement and fiducial marker placement was less than 6 months in 609 patients (91.4%). No patient had a prior recent rectal culture. RESULTS: Ten patients (1.5%) developed a bacterial UTI necessitating hospitalization after transrectal placement of fiducial markers. A bacterial UTI occurred in 3 (0.7%) of 440 patients treated from 2006 to 2012 and in 7 (3.1%) of 226 patients treated from 2013 to 2014. Univariate analysis of potential association of a bacterial UTI with the following parameters revealed: IPSS less than or greater than the median (p=0.3400), diabetes (p=0.6099), tamsulosin (p=0.9999), saw palmetto (p=0.0093), interval between prostate biopsy and placement of fiducials (p=0.9999), year of treatment (p=0.0363), and antibiotics within 6 months (p=0.2233). A bacterial UTI was observed in 4 (6.5%) of 62 patients who were taking saw palmetto versus 6 (1.0%) of 604 patients who were not taking this medication. The incidence of a bacterial UTI between 2006 and 2012 was 3 (0.7%) of 440 patients and from 2013 to 2014 was 7 (3.1%) of 226 patients. Multivariate analysis revealed that the likelihood of a bacterial UTI was increased in patients taking saw palmetto (p=0.0044) and those treated in 2013-2014 (p=0.0303). CONCLUSION: The incidence of a bacterial UTI requiring hospitalization after transrectal placement of fiducial markers prior to proton RT was 1.5% and was impacted by taking saw palmetto and year of treatment. Patients treated during 2013 and 2014 had a significantly higher risk of a bacterial UTI requiring hospitalization.

En Bloc Robot-assisted Laparoscopic Partial Cystectomy, Urachal Resection, and Pelvic Lymphadenectomy for Urachal Adenocarcinoma.

Primary adenocarcinomas of the bladder and urachus are extremely rare, accounting for 0.5% to 2.0% of all bladder malignancies. During fetal development, the urachus develops into the median umbilical ligament that stretches from the umbilicus to the bladder. Adenocarcinoma accounts for 90% of all cases of urachal carcinoma. There is no consensus regarding the management of urachal carcinoma. Although the preferred treatment is wide local excision with partial or radical cystectomy, bladder-sparing management is increasing. We report a case of robot-assisted laparoscopic partial cystectomy with en bloc resection of the urachus and bilateral pelvic lymphadenectomy for urachal carcinoma. The robot-assisted laparoscopic approach allowed us to minimize surgical morbidity, postoperative pain, and convalescent time while maintaining the oncologic principle of wide local excision.

Randomized, Placebo-Controlled Trial of Green Tea Catechins for Prostate Cancer Prevention.

Preclinical, epidemiologic, and prior clinical trial data suggest that green tea catechins (GTC) may reduce prostate cancer risk. We conducted a placebo-controlled, randomized clinical trial of Polyphenon E (PolyE), a proprietary mixture of GTCs, containing 400 mg (-)-epigallocatechin-3-gallate (EGCG) per day, in 97 men with high-grade prostatic intraepithelial neoplasia (HGPIN) and/or atypical small acinar proliferation (ASAP). The primary study endpoint was a comparison of the cumulative one-year prostate cancer rates on the two study arms. No differences in the number of prostate cancer cases were observed: 5 of 49 (PolyE) versus 9 of 48 (placebo), P = 0.25. A secondary endpoint comparing the cumulative rate of prostate cancer plus ASAP among men with HGPIN without ASAP at baseline, revealed a decrease in this composite endpoint: 3 of 26 (PolyE) versus 10 of 25 (placebo), P < 0.024. This finding was driven by a decrease in ASAP diagnoses on the Poly E (0/26) compared with the placebo arm (5/25). A decrease in serum prostate-specific antigen (PSA) was observed on the PolyE arm [-0.87 ng/mL; 95% confidence intervals (CI), -1.66 to -0.09]. Adverse events related to the study agent did not significantly differ between the two study groups. Daily intake of a standardized, decaffeinated catechin mixture containing 400 mg EGCG per day for 1 year accumulated in plasma and was well tolerated but did not reduce the likelihood of prostate cancer in men with baseline HGPIN or ASAP.

Hemorrhagic radiation cystitis.

The optimal management of persistent hemorrhagic radiation cystitis is ill-defined. Various options are available and include oral agents (ie, sodium pentosan polysulfate), intravenous drugs (ie, WF10), topical agents (ie, formalin), hyperbaric oxygen, and endoscopic procedures (ie, electrical cautery, argon plasma coagulation, laser coagulation). In general, it is best to manage patients conservatively and intervene only when necessary with the option least likely to exacerbate the cystitis. More aggressive measures should be employed only when more conservative approaches fail. Bladder biopsies should be avoided, unless findings suggest a bladder tumor, because they may precipitate a complication.

Five-year outcomes from 3 prospective trials of image-guided proton therapy for prostate cancer.

PURPOSE: To report 5-year clinical outcomes of 3 prospective trials of image-guided proton therapy for prostate cancer. METHODS AND MATERIALS: A total of 211 prostate cancer patients (89 low-risk, 82 intermediate-risk, and 40 high-risk) were treated in institutional review board-approved trials of 78 cobalt gray equivalent (CGE) in 39 fractions for low-risk disease, 78 to 82 CGE for intermediate-risk disease, and 78 CGE with concomitant docetaxel therapy followed by androgen deprivation therapy for high-risk disease. Toxicities were graded according to Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Median follow-up was 5.2 years. RESULTS: Five-year rates of biochemical and clinical freedom from disease progression were 99%, 99%, and 76% in low-, intermediate-, and high-risk patients, respectively. Actuarial 5-year rates of late CTCAE, version 3.0 (or version 4.0) grade 3 gastrointestinal and urologic toxicity were 1.0% (0.5%) and 5.4% (1.0%), respectively. Median pretreatment scores and International Prostate Symptom Scores at >4 years posttreatment were 8 and 7, 6 and 6, and 9 and 8, respectively, among the low-, intermediate-, and high-risk patients. There were no significant changes between median pretreatment summary scores and Expanded Prostate Cancer Index Composite scores at >4 years for bowel, urinary irritative and/or obstructive, and urinary continence. CONCLUSIONS: Five-year clinical outcomes with image-guided proton therapy included extremely high efficacy, minimal physician-assessed toxicity, and excellent patient-reported outcomes. Further follow-up and a larger patient experience are necessary to confirm these favorable outcomes.

Comparative effectiveness study of patient-reported outcomes after proton therapy or intensity-modulated radiotherapy for prostate cancer.

BACKGROUND: Data continue to emerge on the relative merits of different treatment modalities for prostate cancer. The objective of this study was to compare patient-reported quality-of-life (QOL) outcomes after proton therapy (PT) and intensity-modulated radiation therapy (IMRT) for prostate cancer. METHODS: A comparison was performed of prospectively collected QOL data using the Expanded Prostate Cancer Index Composite (EPIC) questionnaire. QOL data were collected during the first 2 years after treatment for men who received PT and IMRT. PT was delivered to 1243 men at a single center at doses from 76 grays (Gy) to 82 Gy. IMRT was delivered to 204 men who were included in the Prostate Cancer Outcomes and Satisfaction with Treatment Quality Assessment (PROSTQA) study in doses from 75.6 Gy to 79.4 Gy. The Wilcoxon rank-sum test was used to compare EPIC outcomes by modality using baseline-adjusted scores at different time points. Individual questions were assessed by converting to binary outcomes and testing with generalized estimating equations. RESULTS: No differences were observed in summary score changes for bowel, urinary incontinence, urinary irritative/obstructive, and sexual domains between the 2 cohorts. However, more men who received IMRT reported moderate/big problems with rectal urgency (P = 0.02) and frequent bowel movements (P = 0.05) than men who received PT. CONCLUSIONS: There were no differences in QOL summary scores between the IMRT and PT cohorts during early follow-up (up to 2-years). Response to individual questions suggests possible differences in specific bowel symptoms between the 2 cohorts. These outcomes highlight the need for further comparative studies of PT and IMRT.