Endoscopic sclerotherapy compared with no specific treatment for the primary prevention of bleeding from esophageal varices. A randomized controlled multicentre trial [ISRCTN03215899]

BACKGROUND: Since esophageal variceal bleeding is associated with a high mortality rate, prevention of bleeding might be expected to result in improved survival. The first trials to evaluate prophylactic sclerotherapy found a marked beneficial effect of prophylactic treatment. These results, however, were not generally accepted because of methodological aspects and because the reported incidence of bleeding in control subjects was considered unusually high. The objective of this study was to compare endoscopic sclerotherapy (ES) with nonactive treatment for the primary prophylaxis of esophageal variceal bleeding in patients with cirrhosis. METHODS: 166 patients with esophageal varices grade II, III of IV according to Paquet's classification, with evidence of active or progressive liver disease and without prior variceal bleeding, were randomized to groups receiving ES (n = 84) or no specific treatment (n = 82). Primary end-points were incidence of bleeding and mortality; secondary end-points were complications and costs. RESULTS: During a mean follow-up of 32 months variceal bleeding occurred in 25% of the patients of the ES group and in 28% of the control group. The incidence of variceal bleeding for the ES and control group was 16% and 16% at 1 year and 33% and 29% at 3 years, respectively. The 1-year survival rate was 87% for the ES group and 84% for the control group; the 3-year survival rate was 62% for each group. In the ES group one death occurred as a direct consequence of variceal bleeding compared to 9 in the other group (p = 0.01, log-rank test). Complications were comparable for the two groups. Health care costs for patients assigned to ES were estimated to be higher. Meta-analysis of a large number of trials showed that the effect of prophylactic sclerotherapy is significantly related to the baseline bleeding risk. CONCLUSION: In the present trial, prophylactic sclerotherapy did not reduce the incidence of bleeding from varices in patients with liver cirrhosis and a low to moderate bleeding risk. Although sclerotherapy lowered mortality attributable to variceal bleeding, overall survival was not affected. The effect of prophylactic sclerotherapy seems dependent on the underlying bleeding risk. A beneficial effect can only be expected for patients with a high risk for bleeding

Advances in MRI Assessment of Gliomas and Response to Anti-VEGF Therapy

Bevacizumab is thought to normalize tumor vasculature and restore the blood–brain barrier, decreasing enhancement and peritumoral edema. Conventional measurements of tumor response rely upon dimensions of enhancing tumor. After bevacizumab treatment, glioblastomas are more prone to progress as nonenhancing tumor. The RANO (Response Assessment in Neuro-Oncology) criteria for glioma response use fluid-attenuated inversion recovery (FLAIR)/T2 hyperintensity as a surrogate for nonenhancing tumor; however, nonenhancing tumor can be difficult to differentiate from other causes of FLAIR/T2 hyperintensity (eg, radiation-induced gliosis). Due to these difficulties, recent efforts have been directed toward identifying new biomarkers that either predict treatment response or accurately measure response of both enhancing and nonenhancing tumor shortly after treatment initiation. This will allow for earlier treatment decisions, saving patients from the adverse effects of ineffective therapies while allowing them to try alternative therapies sooner. An active area of research is the use of physiologic imaging, which can potentially detect treatment effects before changes in tumor size are evident

Endoscopic scoring of late rectal mucosal damage after conformal radiotherapy for prostatic carcinoma

Purpose: To describe rectal mucosal damage in an endoscopic study after conformal radiotherapy of prostate cancer and to correlate this with clinical outcome. Materials and methods: Flexible rectosigmoidoscopy was performed on 44 patients who voluntarily accepted the examination. The median follow-up was 29 months (20-41 months) after 3-D-planned conformal radiotherapy of prostate cancer (66 Gy at the ICRU Reference point, 2 Gy per fraction). To enable a systematic topographic description of endoscopic findings the rectum was divided into four sections, Additionally we differentiated between anterior, posterior, right and left lateral rectal wall. Due to the lack of an existing valid graduation system for radiation induced proctitis, pie introduced a six-scaled rectoscopy score for describing and reporting endoscopic findings based on the standardization of the endoscopic terminology published by the ESGE (European Society for Gastrointestinal Endoscopy). Endoscopic findings were compared to the EORTC/RTOG morbidity score. In addition, since 3-D dose distribution of organs at risks was available, a correlation could be made between the location of the rectal lesions and the absorbed dose at that level. Results: In general, endoscopic findings increased from the proximal rectum to the anorectal transition, as well as from the posterior to the anterior rectum wall. Telangiectasia grade 1 and 2 were observed at the whole circumference, only telangiectasia grade 3 were limited to the high dose region at the anterior rectum wall. Similar results were found for congested mucosa (reddening and edematous mucosa). Correlation with symptoms, 7/9 patients who suffered from intermittent rectal bleeding (EORTC/RTOG grade 2) had multiple telangiectasia grade 2-3 and/or congested mucosa grade 3 and microulcerations. However, the same extent of mucosal damage (rectoscopy score 2-3) was found in seven out of 35 patients who have never developed a period of macroscopic rectal bleeding. Conclusion: Rectoscopy offers the possibility of detecting signs of tissue dysfunction below the level of subjective symptoms. Systematic analytic examinations such as rectoscopy, in addition to clinical examinations. as already foreseen in the LENT-SOMA-score, will be necessary due to the fact that even telangiectatic lesions have been observed for asymptomatic patients. For the opportunity of sharing and comparing data collected from endoscopy after radiotherapy a graduation system as proposed based on a standardisation of the endoscopic terminology will be necessary. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved

Rectal sequelae after conformal radiotherapy of prostate cancer: dose-volume histograms as predictive factors

Purpose: To identify clinically relevant parameters predictive of late rectal bleeding derived from cumulative dose-volume histograms (DVHs) of the rectum after conformal radiotherapy of prostate cancer. Materials and methods: One hundred and nine patients treated with 3D conformal radiotherapy between 1/1994 and 1/1996 for localized prostate cancer (clinical stage T1-T3) were available for analysis. All patients received a total dose of 66 Gy/2 Gy per fraction (specified at the International Commission on Radiation Units and Measurements ICRU reference point). DVHs of the contoured rectum were analyzed by defining the absolute (aV) and relative (rV) rectum volume that received more than 30% (V-30), 50% (V-50), 70% (V-70) 80% (V-80), 90% (V-90) and 100% (V-100) of the prescribed dose. Additionally, a new aspect of DVH analysis was investigated by calculation of the area under the DVH-curve between several dose levels (area under the curve (AUC)-DVH). DVH-variables were correlated with radiation side effects evaluated in 3-6 months intervals and graded according to the EORTC/RTOG score. The median follow-up was 30 months (12-60 months). Results: Univariate and multivariate stepwise Cox-Regression analysis including age, PTV, rectum size, rV(100), rV(90), rV(80), rV(70); rV(50) rV(30) and aV(30), to aV(100) were calculated. Late rectal bleeding (EORTC/RTOG grade 2) was significantly correlated with the percentage of rectum volume receiving greater than or equal to 90% of the prescribed dose (rV(90)) (P = 0.007) and inversely correlated in a significant way with the size of contoured rectum (P = 0.006) in multivariate analysis. In our series, a proportion of the rectum volume greater than or equal to 57% were included in the 90%-isodose (rV(90) greater than or equal to 57%) in one half of the patients, with an actuarial incidence of 31% of late rectal bleeding at 3 years. In the other half of the patients, when rV(90) < 57%, the 3-year actuarial incidence was 11% (P < 0.03). Conclusion: Our data demonstrate a dose-volume relationship at the reference dose of 60 Gy (similar to 90% of the prescribed dose) with respect to late rectal toxicity. The rV(90) seems to be the most useful and easily obtained parameter when comparing treatment plans to evaluate the risk of rectal morbidity. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved