Luigi Pagliaro

Portal hypertension is a major complication of chronic liver disease. Its main clinical consequence, bleeding from ruptured esophagogastric varices, represents a dramatic medical emergency, with mortality rate ranging from 30% to 50%, and is one of the leading causes of death in patients with cirrhosis.'-'

Continuing advances in the knowledge of the pathophysiology of portal hypertension result in the progressive expansion of the spectrum of drugs with a potential role for clinical practice, with objectives that now tend to include the prevention of the enlargement or even the development of esophageal varices. This systematic review summarizes the evidence of efficacy of drug therapy for portal hypertension and draws recommendations for clinical practice. Although there is not yet enough evidence to support the treatment for the prevention of the development or enlargement of varices, nonselective beta-blockers are the first-choice therapy to prevent the first bleeding in patients with medium or large-sized varices and rebleeding in patients surviving a bleeding episode. The clinical role of isosorbide-5-mononitrate either alone or in association with beta-blockers still remains unsettled. Vasoactive drugs are generally effective and safe in controlling acute variceal bleeding, although the evidence is not equivalent for each of them.

CONTEXT: The benefit of adjuvant radiotherapy for resectable rectal cancer has been extensively studied, but data on survival are still equivocal despite a reduction in the rate of local recurrence. OBJECTIVE: To assess the effectiveness of preoperative radiotherapy followed by surgery in the reduction of overall and cancer-related mortality and in the prevention of local recurrence and distant metastases. DATA SOURCES: Computerized bibliographic searches of MEDLINE and CANCERLIT (1970 to December 1999), including non-English sources, were supplemented with hand searches of reference lists. The medical subject headings used were rectal cancer, radiotherapy, surgery, RCT, randomized, and clinical trial. STUDY SELECTION: Studies were included if they were randomized controlled trials (RCTs) comparing preoperative radiotherapy plus surgery with surgery alone and if they included patients with resectable histologically proven rectal adenocarcinoma, without metastatic disease. Fourteen RCTs were analyzed. DATA EXTRACTION: Data on population, intervention, and outcomes were extracted from each RCT according to the intention-to-treat method by 3 independent observers and combined using the DerSimonian and Laird method. DATA SYNTHESIS: Radiotherapy plus surgery compared with surgery alone significantly reduced the 5-year overall mortality rate (odds ratio [OR] 0.84; 95% confidence interval [CI], 0.72-0.98; P =.03), cancer-related mortality rate (OR, 0.71; 95% CI, 0.61-0.82; P<.001), and local recurrence rate (OR, 0.49; 95% CI, 0.38-0.62; P<.001). No reduction was observed in the occurrence of distant metastases (OR, 0.93; 95% CI, 0.73-1.18; P =.54). CONCLUSIONS: In patients with resectable rectal cancer, preoperative radiotherapy significantly improved overall and cancer-specific survival compared with surgery alone. The magnitude of the benefit is relatively small and criteria are needed to identify patients most likely to benefit from adjuvant radiotherapy. JAMA. 2000;284:1008-1015