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Background Local‐regional failure (LF) for locally advanced bladder cancer (LABC) after radical cystectomy (RC) is common even with chemotherapy and is associated with high morbidity/mortality. Postoperative radiotherapy (PORT) can reduce LF and may enhance overall survival (OS) but has no defined role. We hypothesized that the addition of PORT would improve OS in LABC in a large nationwide oncology database. Methods We identified ≥ pT3pN0‐3M0 LABC patients in the National Cancer Database diagnosed 2004‐2014 who underwent RC ± PORT. OS was calculated using Kaplan‐Meier and Cox proportional hazards regression modeling was used to identify predictors of OS. Propensity matching was performed to match RC patients who received PORT vs those who did not. Results 15,124 RC patients were identified with 512 (3.3%) receiving PORT. Median OS was 20.0 months (95% CI, 18.2‐21.8) for PORT vs 20.8 months (95% CI, 20.3‐21.3) for no PORT (P = 0.178). In multivariable analysis, PORT was independently associated with improved OS: hazard ratio 0.87 (95% CI, 0.78‐0.97); P = 0.008. A one‐to‐three propensity match yielded 1,858 patients (24.9% receiving PORT and 75.1% without). In the propensity‐matched cohort, median OS was 19.8 months (95% CI, 18.0‐21.6) for PORT vs 16.9 months (95% CI, 15.6‐18.1) for no PORT (P = 0.030). In the propensity‐matched cohort of urothelial carcinoma patients (N = 1,460), PORT was associated with improved OS for pT4, pN+, and positive margins (P

Objective To examine prostate cancer (PCa) incidence and mortality by arm in the randomized Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial. Patients and methods Patients aged 55-74 years at 10 screening centres were randomized between 1993 and 2001 to an intervention or usual care arm. Patients in the intervention arm received six annual prostate-specific antigen (PSA) tests and four annual digital rectal examinations. The patients were followed for PCa incidence and for mortality via active follow-up processes and by linkage to state cancer registries and the National Death Index. For cancers identified through active follow-up, trial abstractors recorded the mode of diagnosis (screen-detected, symptomatic, other). Results A total of 38 340 patients were randomized to the intervention arm and 38 343 to a usual care arm. The median follow-up for mortality was 16.9 (intervention) and 16.7 years (usual care). There were 333 (intervention) and 352 (usual care) PCa cancer deaths, giving rates (per 10 000 person-years) of 5.5 and 5.9, respectively, and a rate ratio (RR) of 0.93 (95% confidence interval [CI] 0.81-1.08; P = 0.38). The RR for overall PCa incidence was 1.05 (95% CI 1.01-1.09). The RRs by Gleason category were 1.17 (95% CI 1.11-1.23) for Gleason 2-6, 1.00 (95% CI 0.93-1.07) for Gleason 7 and 0.89 (95% CI 0.80-0.99) for Gleason 8-10 disease. By mode of detection, during the trial's screening phase, 13% of intervention arm vs 27% of usual care arm cases were symptomatic; post-screening, these percentages were 18% in each arm. Conclusion After almost 17 years of median follow-up, there was no significant reduction in PCa mortality in the intervention compared with the usual care arm. There was a significant increase in Gleason 2-6 disease and a significant reduction in Gleason 8-10 disease in the intervention compared with the usual care arm.

Objective To characterise the surgical feasibility and outcomes of robot-assisted radical cystectomy (RARC) for pathological T4 bladder cancer. Patients and Methods Retrospective evaluation of a prospectively maintained International Radical Cystectomy Consortium database was conducted for 1118 patients who underwent RARC between 2003 and 2012. We dichotomised patients based on pathological stage (≤pT3 vs pT4) and evaluated demographic, operative and pathological variables in relation to morbidity and mortality. Results In all, 1000 ≤pT3 and 118 pT4 patients were evaluated. The pT4 patients were older than the ≤pT3 patients (P = 0.001). The median operating time and blood loss were 386 min and 350 mL vs 396 min and 350 mL for p T4 and ≤pT3, respectively. The complication rate was similar (54% vs 58%; P = 0.64) among ≤pT3 and pT4 patients, respectively. The overall 30- and 90-day mortality rate was 0.4% and 1.8% vs 4.2% and 8.5% for ≤pT3 vs pT4 patients (P < 0.001), respectively. The body mass index (BMI), American Society of Anesthesiology score, length of hospital stay (LOS) >10 days, and 90-day readmission were significantly associated with complications in pT4 patients. Meanwhile, BMI, LOS >10 days, grade 3–5 complications, 90-day readmission, smoking, previous abdominal surgery and neoadjuvant chemotherapy were significantly associated with mortality in pT4 patients. On multivariate analysis, BMI was an independent predictor of complications in pT4 patients, but not for mortality. Conclusions RARC for pT4 bladder cancer is surgically feasible but entails significant morbidity and mortality. BMI was independent predictor of complications in pT4 patients.

BACKGROUND Follow-through of a positive screening test is necessary to reap the potential benefits of cancer screening. Racial variation in follow-through diagnostic care may underlie a proportion of the known disparity in prostate cancer mortality. The authors used data from the screening arm of the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial to determine whether race is associated with the use of follow-up diagnostic testing after a positive initial screening evaluation. METHODS Men who had a prostate-specific antigen (PSA) level >4 ng/mL at any time during the study were included. The proportion of men who underwent follow-up evaluation with a repeat PSA, a prostate biopsy, or either test within 9 months was determined, and the authors tested for differences in follow-through according to race using mixed-effects multivariate models with a random effect for accrual site to account for clustering. Models were stratified according to age (

BACKGROUND. Two recent chemoprevention trials demonstrated significant reductions in overall prostate cancer incidence. However, a possible increase in high-grade disease has raised concerns that the harms of the drugs, including mortality because of high-grade disease, may outweigh the benefits. The authors attempted to estimate the effect of these drugs on prostate cancer mortality to be able to better evaluate the cost-benefit tradeoff. METHODS. The authors analyzed prostate cancer incidence in the Prostate Cancer Prevention Trial (PCPT) and Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial, which evaluated finasteride and the related compound dutasteride, respectively (both vs placebo). They used 13-year prostate cancer survival data from the Prostate, Lung, Colorectal and Ovarian (PLCO) trial to project prostate cancer mortality from incidence patterns; survival rates were applied to incident cancers according to prognostic strata, which were defined by Gleason score, prostate-specific antigen level, and clinical stage. For PCPT, the analysis was performed using both original trial results and previously published adjusted analyses that attempted to account for artifacts related to the drugs' effect on prostate volume. RESULTS. For the PCPT trial, the estimated relative risk (RR) for prostate cancer mortality was 1.02 (95% confidence interval [95% CI], 0.85-1.23) using the original trial results and 0.87 (95% CI, 0.72-1.06) and 0.91 (95% CI, 0.76-1.09) based on the adjusted PCPT analyses. For the REDUCE trial, the RR for prostate cancer mortality was 0.93 (95% CI, 0.80-1.08). CONCLUSIONS. Projecting a mortality outcome of the PCPT and REDUCE trials as an approach to weighing benefits versus harms suggests at most a small increase in prostate cancer mortality in the treatment arms, and possibly a modest decrease. Cancer 2013. © 2012 American Cancer Society.

Objectives To investigate the relationship between non-steroidal anti-inflammatory drug (NSAID) use and the incidence of benign prostatic hyperplasia (BPH)-related outcomes and nocturia, a lower urinary tract symptom (LUTS) of BPH, in light of accumulating evidence suggesting a role for inflammation in BPH/LUTS development. Patients and methods At baseline, participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial completed questions on recent, regular aspirin and ibuprofen use, BPH surgery, diagnosis of an enlarged prostate/BPH, and nocturia. Participants in the intervention arm also underwent a digital rectal examination (DRE), from which prostate dimensions were estimated, as well as a prostate-specific antigen (PSA) test. Only participants in the intervention arm without BPH/LUTS at baseline were included in the analysis (n = 4771). During follow-up, participants underwent annual DREs and PSA tests, provided annual information on finasteride use, and completed a supplemental questionnaire in 2006–2008 that included additional questions on diagnosis of an enlarged prostate/BPH and nocturia. Information collected was used to investigate regular aspirin or ibuprofen use in relation to the incidence of six BPH/LUTS definitions: diagnosis of an enlarged prostate/BPH, nocturia (waking two or more times per night to urinate), finasteride use, any self-reported BPH/LUTS, prostate enlargement (estimated prostate volume ≥ 30 mL on any follow-up DRE) and elevation in PSA level (> 1.4 ng/mL on any follow-up PSA test). Results Generally, null results were observed for any recent, regular aspirin or ibuprofen use (risk ratio = 0.92–1.21, P = 0.043–0.91) and frequency of use (risk ratio for one category increase in NSAID use = 0.98–1.11, P-trends = 0.10–0.99) with incident BPH/LUTS. Conclusions The findings obtained in the present study do not support a protective role for recent NSAID use in BPH/LUTS development. Keywords: aspirin, benign prostatic hyperplasia, ibuprofen, lower urinary tract symptoms, non-steroidal anti-inflammatory drugs Introduction BPH is a common condition of ageing men characterized histologically by hyperplastic nodules in the peri-urethral region and transition zone of the prostate, and clinically by a palpably enlarged prostate and LUTS [1]. Accumulating evidence suggests that inflammation may be involved in BPH/LUTS development [2]. In rodent models, induced prostatic inflammation has been shown to contribute to prostatic hyperplasia [3,4], whereas, in humans, inflammatory infiltrates are frequently observed in prostate tissue specimens from men with BPH [5–8] and the presence or degree of inflammation has been found to be correlated with prostate volume/weight [8,9], LUTS severity [10] and surgery for acute urinary retention independent of urinary tract infection [9]. Finally, in a trial of BPH/LUTS therapy, chronic prostatic inflammation was associated with a greater risk of clinical BPH progression and subsequent acute urinary retention [11]. Given these observations suggesting that inflammation may contribute to BPH/LUTS, it is plausible to hypothesize that anti-inflammatory agents (e.g. NSAIDs) may reduce the risk of BPH/LUTS [12]. To our knowledge, only three previous studies have investigated the association between NSAID use and BPH/LUTS. The first of these studies observed no association between aspirin use and prevalent BPH/LUTS; however, the results were unstable as a result of low numbers of aspirin users [13]. The second study, conducted in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, observed a weak positive association between regular NSAID use and prevalent BPH/LUTS [14], whereas the third study, conducted in the Olmsted County Study of Urinary Symptoms and Health Status among Men, observed a strong inverse association between daily NSAID use and incident BPH/LUTS [12]. Given these strong latter findings for risk (as opposed to the prevalence) of BPH/LUTS, we have now extended the previous analysis in the PLCO to investigate NSAID use in relation to risk of BPH/LUTS.

Summary Purpose: The short-term efficacy and safety of epilepsy surgery relative to medical therapy has been established, but it remains underutilized. There is a lack of data regarding the long-term seizure-control rates and quality of life outcomes after epilepsy surgery. This study represents the longest follow-up study to date, with a mean follow-up duration of 26 years. Methods: We studied the seizure and health-related quality of life outcomes of patients who underwent epilepsy surgery by Dr. Sidney Goldring from 1967 to 1990. Retrospective clinical chart reviews gathered perioperative data and surveys obtained follow-up data. Seizure outcome was evaluated using the Engel classification system. Key Findings: Of 361 patients, 117 (32.4%) completed follow-up interviews. Fifty-six patients (48%) were Engel class I. Mean overall Quality of Life in Epilepsy (QOLIE-31) questionnaire score for the cohort was 68.2 ± 16. Eighty percent of patients reported their overall quality of life now as being better than before surgery. Seizure freedom was associated with better quality of life. We did not observe a statistically significant association between postoperative complications and long-term outcome. Patients who underwent temporal lobe resection achieved better seizure outcomes than those who underwent other types of procedures. Astatic seizures and bilateral surgery were associated with a worse Engel class outcome. Significance: Our study demonstrates that the beneficial effects of epilepsy surgery are sustained over decades, and that these beneficial effects are correlated with an improved quality of life. The confirmation of its durability makes us optimistic that the outcomes from modern epilepsy surgery will be even better and that our present enthusiasm for this treatment modality is not misplaced.

This review provides a perspective of spinal injuries related to invasive cardiology, an understanding of the anatomy and physiology of the spine, the etiology and pathophysiology of spinal injuries, and options for prevention and treatment. In this part of our review, conventional surgical and minimally invasive options are discussed as well as emerging techniques for the treatment of back pain. We also discuss methods of preventing back injuries by modifications to the work environment as well as preventive measures that may be practiced by the invasive cardiologist. Our final objective is to describe and illustrate proven techniques for strengthening the supportive musculature to avoid spinal injury as well as to reduce painful exacerbations.

OBJECTIVE To determine patterns of repeat prostate biopsy in a cohort of men undergoing prostate cancer screening who have a negative initial biopsy. SUBJECTS AND METHODS The Prostate, Colorectal, Lung, and Ovarian (PLCO) cancer screening trial is an ongoing study the prostate component of which consists of six annual screens with measurements of prostate-specific antigen (PSA) level and a digital rectal examination (DRE). The diagnostic follow-up of positive screening results is done by the subject's healthcare provider outside the purview of the PLCO. We analysed the experience of repeat biopsy in men in the PLCO with an initial negative biopsy. Men were divided by indication for initial biopsy into those with suspicious PSA levels and those with suspicious DRE findings. RESULTS The probability of having a repeat biopsy within 3 years of initial biopsy was 43% for 1736 men with suspicious PSA levels and 13% for 1025 men with suspicious DRE findings. Rates of third and fourth biopsy after a previous negative biopsy were similar to the initial repeat biopsy rate in PSA-positive men. Most men had a repeat biopsy only after having an additional round of screening. The PSA level and PSA velocity determined after initial biopsy were independent risk factors for a repeat biopsy, both in PSA-positive and DRE-positive men. High-grade prostatic intraepithelial neoplasia was a risk factor for repeat biopsy before any repeat PSA or DRE testing. CONCLUSION The experience of this cohort should be generally representative of patterns of care for repeat biopsy in men undergoing periodic screening. These data can provide context to the debate over optimum practices for repeat biopsy.

Reverse phase protein arrays represent a new proteomics microarray technology with which to study the fluctuating state of the proteome in minute quantities of cells. The activation status of cell signaling pathways controls cellular fate and deregulation of these pathways underpins carcinogenesis. Changes in pathway activation that occur between early stage prostatic epithelial lesions, prostatic stroma and the extracellular matrix can be analyzed by obtaining pure populations of cell types by laser capture microdissection (LCM) and analyzing the relative states of several key phosphorylation points within the cellular circuitry. We have applied reverse phase protein array technology to analyze the status of key points in cell signaling involved in pro-survival, mitogenic, apoptotic and growth regulation pathways in the progression from normal prostate epithelium to invasive prostate cancer. Using multiplexed reverse phase protein arrays coupled with LCM, the states of signaling changes during disease progression from prostate cancer study sets were analyzed. Focused analysis of phospho-specific endpoints revealed changes in cellular signaling events through disease progression and between patients. We have used a new protein array technology to study specific molecular pathways believed to be important in cell survival and progression from normal epithelium to invasive carcinoma directly from human tissue specimens. With the advent of molecular targeted therapeutics, the identification, characterization and monitoring of the signaling events within actual human biopsies will be critical for patient-tailored therapy.

Advanced tumors of the paranasal sinuses, parotid gland, orbit, parapharynx, and cranial cavity may invade the infratemporal fossa by direct extension or through natural anatomic pathways. The inability to control disease involving this region is reflected by the unacceptably high recurrence rates for both intracranial and extracranial neoplasms. Between 1983 and 1986, a pterional (or subtemporal) approach was combined with such conventional anterolateral procedures as a mandibulopharyngectomy, maxillectomy, orbitectomy, and parotidectomy in 13 patients with advanced skull base lesions. The tumor origin was extracranial in ten cases and intracranial in three patients. Seven of the neoplasms were malignant and six were histologically benign. Complete tumor removal was achieved in all patients. Repair of the ablative defect was achieved with a temporalis myogenous flap in ten patients, and primary closure or distant myocutaneous flaps in the remaining three patients. Postoperative complications included three lateral nasocutaneous fistulae secondary to temporalis myogenous flap necrosis and isolated cases of stroke, cerebral edema, pneumocephalus, and cerebrospinal fluid rhinorrhea. Twelve patients are alive without evidence of disease at a mean interval of 25 months. The remaining patient died from lung metastases 11 months after surgery.

A comprehensive analysis of cerebral hemodynamics and metabolism was carried out in 14 patients with pseudotumor cerebri. Tracer techniques were employed to measure cerebral blood flow (CBF) and vascular reactivity to acute changes in arterial carbon dioxide tension and blood pressure, cerebral blood volume (CBV), and the cerebral metabolic rate for oxygen and glucose. There was a small reduction (p less than 0.01) in CBF (44 +/- 7 ml/100 gm/min; normal, 54 +/- 9) with normal vascular reactivity; an increase (p less than 0.005) in CBV (4.8 +/- 0.8 ml/100 gm; normal, 3.6 +/- 0.5), and normal cerebral metabolism. We conclude that an abnormality of the cerebral microvasculature is responsible for an elevation in CBV, but the intracranial hypertension can be explained only by tissue swelling due to an increase in water content. The relationship between the vascular abnormality and the tissue swelling remains to be defined.

The technique of positron emission tomography was used to measure cerebral blood volume (CBV) in 10 normal right-handed human volunteers following inhalation of trace quantities of cyclotron-produced, 11C-labeled carbon monoxide. In scans obtained 4 cm above the orbitomeatal line, CBV was 4.3 ml per 100 gm of tissue, whereas in scans obtained 8 cm above the orbitomeatal line, CBV was significantly less (3.3 ml per 100 gm; p less than 0.001). This difference reflects the greater proportion of gray matter in the lower scan. Furthermore, the CBV was significantly larger (p less than 0.001) in the left cerebral hemisphere in the tomographic scans obtained 4 cm above the orbitomeatal line. These scans include the region of the superior surface of the temporal lobe (planum temporale), which is thought to be larger in individuals with left cerebral dominance for speech. This observation is the first in vivo demonstration of a structural correlate of a known functional difference in the cerebral hemispheres of man.