Faculty Bibliography

OBJECTIVE:To report the outcomes and late toxicities in younger patients with long-term follow-up treated with brachytherapy with or without external beam radiotherapy for prostate adenocarcinoma. MATERIALS AND METHODS/METHODS:Patients treated with brachytherapy with or without external beam radiotherapy who were aged ≤ 60 years at treatment with ≥ 10 years of follow-up were selected from our database. The outcomes were analyzed regarding biochemical failure, distant metastases, and cause of death. Genitourinary outcomes were assessed using the International Prostate Symptom Score, Radiation Therapy Oncology Group, and Common Terminology Criteria for Adverse Events criteria. Gastrointestinal toxicity was measured using Radiation Therapy Oncology Group scales. Erectile dysfunction was measured using Sexual Health Inventory for Men and the Mount Sinai Erectile Function score. RESULTS:A total of 131 patients met the inclusion criteria, with a median age of 57 years at treatment and a median follow-up of 11.5 years. Of the patients in this cohort, 9.9% developed biochemical failure with 1 failure and 1 prostate cancer-related death after 10 years. The International Prostate Symptom Score were statistically unchanged after 10 years. Of 22 cases (17%) of grade 2 or greater genitourinary toxicities, only 6 (4.5%) continued after 10 years. Of 11 cases (8.3%) of grade 2 or greater gastrointestinal events, none persisted past 10 years. A significant decrease occurred in the mean Sexual Health Inventory for Men score from 19.5 to 15.3 (P = .008). Of the potent patients before treatment, 69% remained potent at last follow-up. A total of 4 second malignancies were detected, 2 of which were within the radiation field. CONCLUSION/CONCLUSIONS:Men <60 years old who underwent brachytherapy for prostate cancer can expect minimal late genitourinary and gastrointestinal toxicity after 10 years and excellent potency preservation.

PURPOSE/OBJECTIVE:To evaluate the efficacy of multimodality therapy consisting of hormone therapy (HT), brachytherapy (BT), and external beam radiotherapy (EBRT) in extraprostatic prostate cancer and identify factors with predictive value. METHODS AND MATERIALS/METHODS:Between June 1992 and October 2006, 97 patients with extraprostatic prostate cancer received permanent seed implant BT. Extraprostatic disease was defined by one or more of the following: positive seminal vesicle biopsy (n=56), positive lymph node dissection (n=8), or a clinical tumor stage of T3 (n=48). Treatment consisted of BT alone with (103)Pd or (125)I (n=4); HT and BT (n=3); BT and EBRT (n=2); or trimodality therapy with HT, BT, and EBRT (n=88). Median followup was 69 (range, 23-182) months. Freedom from biochemical failure (FBF) rates were calculated using the Phoenix criteria. RESULTS:The 7-year actuarial FBF, freedom from distant metastases, disease-specific survival, and overall survival rates were 67%, 82%, 96%, and 81%, respectively. Biologically effective dose (BED) was the only variable significantly impacting FBF rates. FBF at 7 years was 60% vs. 74% for BED below 200 and 200 or above, respectively (p=0.048). Trends toward worse outcomes were noted with increasing Gleason score, with 7-year FBF rates of 86% vs. 71% vs. 55% for scores of 6 or less, 7, and 8-10, respectively (p=0.090). BED was the only significant predictor of FBF in multivariate analysis (p=0.032). None of the predictors were significant in multivariable analyses for the other outcomes studied. CONCLUSIONS:Trimodality approach achieves durable biochemical control in most patients with historically poor prognosis T3 prostate cancer. BED above 200Gy was associated with superior FBF.

Acute lung injury remains a major cause of morbidity and mortality in paediatric intensive care units. Research over the past decade has altered our understanding of the pathophysiology of acute lung injury and the effects of mechanical ventilation on the lung. As a result, approaches to conventional mechanical ventilation of the injured lung are now largely centred around preservation of adequate gas exchange while protecting the lung from further ventilator-induced lung injury. Current techniques for accomplishing these goals include adjusting the ventilator based on the measurement and interpretation of pressure-volume curves, limitation of inspiratory tidal volumes, use of elevated levels of positive end-expiratory pressure, recruiting manoeuvres and prone positioning. The currently available data regarding the efficacy and appropriate use of these techniques are reviewed.

Endothelin (ET) may contribute to pulmonary edema formation, particularly under hypoxic conditions, and decreases in ET-B receptor expression can lead to reduced ET clearance. ET increases vascular endothelial cell growth factor (VEGF) production in vitro, and VEGF overexpression in the lung causes pulmonary edema in vivo. We hypothesized that pulmonary vascular ET-B receptor deficiency leads to increased lung ET, that excess ET increases lung VEGF levels, promoting pulmonary edema formation, and that hypoxia exaggerates these effects. We studied these hypotheses in ET-B receptor-deficient rats. In normoxia, homozygous ET-B-deficient animals had significantly more lung vascular leak than heterozygous or control animals. Hypoxia increased vascular leak regardless of genotype, and hypoxic ET-B-deficient animals leaked more than hypoxic control animals. ET-B-deficient animals had higher lung ET levels in both normoxia and hypoxia. Lung HIF-1alpha and VEGF content was greater in the ET-B-deficient animals in both normoxia and hypoxia, and both HIF-1alpha and VEGF levels were reduced by ET-A receptor antagonism. Both ET-A receptor blockade and VEGF antagonism reduced vascular leak in hypoxic ET-B-deficient animals. We conclude that ET-B receptor-deficient animals display an exaggerated lung vascular protein leak in normoxia, that hypoxia exacerbates that leak, and that this effect is in part attributable to an ET-mediated increase in lung VEGF content.