Propranolol for the prevention of first esophageal variceal hemorrhage: a lifetime commitment?

Although beta blockers have had significant impact in the treatment of portal hypertension, the question of how long they should be continued for prevention of variceal hemorrhage remains unknown. Prospective studies on beta blockers to prevent variceal hemorrhage lack long-term follow-up, and indefinite administration of beta blockers for primary prevention of variceal bleeding has become standard practice. The aim of this study was to determine the outcomes of patients in whom beta blocker therapy was discontinued. Patients completing a prospective, randomized, double-blind, placebo-controlled trial of propranolol for the primary prevention of variceal hemorrhage were tapered off of propranolol and placebo and followed prospectively for subsequent events. Of the 49 patients in the follow-up study (25 former propranolol, 24 former placebo), 9 experienced variceal hemorrhage (6 former propranolol, 3 former placebo). Following withdrawal of propranolol, the freedom from variceal bleeding was not significantly different between these 2 groups of patients, suggesting that the protective effect of propranolol against variceal hemorrhage, noted previously, was no longer present. Seventeen patients died (12 former propranolol, 5 former placebo) during the follow-up study. Cumulative survival was longer in the placebo group. These trends for EVH and survival were opposite to those observed in the original study population while patients were taking medication. When propranolol is withdrawn, the risk of variceal hemorrhage returns to what would be expected in an untreated population. Patients who discontinue beta blockers experience increased mortality compared with an untreated population. These observations support the current practice of indefinite prophylactic therapy.

Intestinal transplantation for the treatment of desmoid tumors associated with familial adenomatous polyposis.

BACKGROUND: Desmoid tumors associated with familial adenomatous polyposis (FAP) are locally invasive. Often occurring in the mesentery of the intestine, they sometimes recur after resection. Complications can include intestinal failure and dependence on parenteral nutrition. We describe 9 patients who underwent intestinal transplantation for the treatment of desmoid tumors associated with FAP. METHODS: Records of patients undergoing intestinal transplantation for desmoid tumors at 2 transplant centers were reviewed for patient age, sex, type of graft, procedure date, tumor site, desmoid complications, medications, extracolonic manifestations, status at follow-up, and length of survival. RESULTS: Nine patients with FAP and intestinal failure caused by desmoid tumors were treated with isolated intestinal (n = 6), multivisceral (n = 2), or combined liver-intestinal transplantation (n = 1). Desmoid tumors recurred in the abdominal walls of 2 patients. Two patients died: one as a result of sepsis, the other because of a rupture of a mycotic aneurysm of the aortic anastomosis. One graft lost to severe rejection was replaced with a second intestinal graft. Eleven to 53 months after transplantation, 7 patients were alive, well, independent of parenteral treatment, and leading apparently normal lifestyles. CONCLUSIONS: Transplantation of the intestine alone or as part of a multivisceral transplantation may help rescue otherwise untreatable patients with complicated desmoid tumors.

Hyperammonemia and intracranial hypertension: lying in wait for patients with hepatic disorders?

In the past decade, a dozen patients with acute liver injury, with idiopathic hyperammonemia and intracranial hypertension in the absence of acute liver failure have been reported, as discussed below. If one combines these patients to those with acute liver failure and Reye's syndrome, in both of which cerebral herniation is a common complication, liver disease may be one of the most common causes of cerebral herniation. Indeed, these reports have similarities to the patients of Clemmesen et al. who found that increased blood ammonia levels are frequently elevated, which led to the observation that increased blood ammonia concentrations may be early warning signs of impending cerebral herniation.

Portal hypertension, varices, and transjugular intrahepatic portosystemic shunts.

Transjugular intrahepatic protosystemic shunts (TIPS) is the newest and the least invasive method of eradicating varices. This article defines portal hypertension succinctly, describes how it gives rise to varices and their consequences, and briefly reviews the development, short experience with, and current status of TIPS.

Recurrent Crohn's disease in transplanted bowel.

BACKGROUND: Intestinal transplantation is used in patients with short-bowel syndrome after repeated resections for Crohn's disease. We report the apparent clinical recurrence of Crohn's disease in a transplanted intestine. METHODS AND FINDINGS: The patient, a 33-year-old Hispanic woman, underwent small-bowel transplantation in December, 1994. Immunosuppression with tacrolimus, methylprednisolone, bone-marrow infusions, and OKT3 was given. In July, 1995, the patient had recurrent abdominal symptoms. The histological diagnosis of Crohn's disease was established by the independent interpretations of four experienced gastrointestinal histopathologists. INTERPRETATION: The prompt appearance of this autoimmune disorder (within 6 months of transplantation), despite massive immunosuppression may provide important insights into the nature of Crohn's disease and of the recurrence of autoimmune disease during immunosuppression.

Interpretation of data from multiple trials: a critical review.

The objective was to review the current status of meta-analysis, the process of combining the results of similar investigations, which was described in 1976. It has evolved rapidly, and thousands have already been published. Meta-analysis may be performed in a narrative form or in the preferred statistical format, which is more rigorous and demanding. The criteria for designing and performing a meta-analysis of high quality are presented and discussed in detail, including selection criteria, quality, biases and heterogeneity, both of component studies and of results. Critical reviews of meta-analyses are presented. Examples are given from my own field--hepatology--and from my own research experience. Although meta-analysis is simple in concept, it is complex in execution. If performed with insufficient insight or attention to detail, it may give ambiguous or erroneous results.

The treatment of oesophageal varices: a debate and a discussion.

At the Biennial Meeting of the International Association for the Study of the Liver, in Cape Town, South Africa, 20-24 February 1996, the treatment of oesophageal varices was selected as a subject for the discussion of controversies in portal hypertension. This review gives a summary of that discussion. Dr Didier LeBrec gave a broad overview of the medical management of oesophageal varices by presenting a list of 52 pharmacological agents that reduce portal venous pressure and presented the advantages and disadvantages of each. He emphasized that recent randomized clinical trials (RCT) have demonstrated that propranolol delays and decreases the occurrence of haemorrhage from varices in patients who have not previously suffered such complications. He also reported that isosorbidemononitrate is equally effective and further enhances the effect of propranolol. He also reported that the effects of propranolol plus endoscopic sclerotherapy (EST) were more effective than EST alone in preventing haemorrhage, but not in improving survival. Finally he noted that propranolol in high dosage did not prevent the development of large varices in cirrhotic patients with small or undetectable varices. Dr John Terblanche compared the efficacy of EST and endoscopic ligation of varices (ELV) and reported that all four RCTs found ELV to be superior. He discussed portacaval anastomosis (PCA) and concluded that only emergency PCA as reported by Orloff, is thought to be truly beneficial, and suggested that EST, plus ELV may be the treatment of choice. Dr Harold O. Conn, who served as the moderator of this session summarized the presentations and pointed out that liver transplantation is the most effective form of therapy of all, albeit extremely complex and expensive. He discussed transjugular intrahepatic portosystemic shunts (TIPS), the newest form of therapy, and emphasized its virtues (immediate reduction of portal venous pressure) and its limitations (frequent portosystemic encephalopathy and frequent spontaneous stenoses). He presented a brief discussion of the prevention of the development of the varices themselves, currently termed "pre-primary prophylaxis', a hope for the future. He ended with "Predictions' which if proven correct will give a preview of portal hypertension in the 21st century.

A clinical hepatologist's predictions about non-absorbed carbohydrates for the early twenty-first century.

To put these predictions into perspective, the primary indication for lactulose therapy in the treatment of HE and SHE is presented and discussed. Six secondary indications for lactulose therapy are also listed and briefly commented upon. A dozen predictions about the status of lactulose are presented and briefly discussed. A. Lactulose will be the treatment of choice for HE.B. TIPS will be the most common cause of HE.C. Lactulose will not be approved in Mexico. D. Lactulose plus anti-diarrheal drugs will be agents for treatment of HE. E. Lactulose will not be the treatment of choice for constipation. F. Lactulose will not be used for Salmonella or Shigella carrier states. G. Lactulose will be routinely administered prophylactically after TIPS. H. Lactulose will be administered prophylactically to cirrhotic patients with portal hypertension. I. Lactulose plus anti-diarrheal drugs will be used for a variety of diverse purposes: (i) Suppression of bacterial growth; (ii) prevention of bacteriuria; (iii) diminution of cholesterol saturation of bile; (iv) adjunct treatment of gallstones with ursodeoxycholic acid; (v) Prevention of colon carcinoma.

Determination of ammonia in ear-lobe capillary blood is an alternative to arterial blood ammonia.

Blood ammonia determination is a laboratory test to diagnose hepatic encephalopathy. Arterial blood is superior to peripheral venous blood ammonia because of ammonia metabolism in muscle. We have compared capillary with arterial whole blood ammonia as capillary sampling is an attractive alternative. Ear-lobe capillary blood ammonia (ECA) was determined in all 173 persons studied, fingertip capillary blood ammonia (FCA) in 46 of these and arterial blood ammonia (AA) in 113. Of the 173, 60 were healthy (H), 64 were patients, not liver diseased (NLD) and 49 had liver disease (LD). Reference values, median and ranges, mumol NH3-N/l: AA, NLD, n = 64: 17 (7-42); ECA, H = NLD (P = 0.9), n = 124: 20 (7-45); FCA, H = NLD (P = 0.8), n = 33: 70 (29-151). Within the NLD group (n = 64) AA values (range 7-42) were little but significantly lower than the ECA values (range 7-45, P = 0.002). FCA NLD > AA NLD (n = 14, P < 0.0001); FCA H+NLD > ECA (n = 33, P < 0.0001). AA correlated very well with ECA, r = 0.87 (n = 113, P < 0.0001) and less well with FCA, r = 0.56 (n = 27, P < 0.01). ECA correlated with FCA, r = 0.51 (n = 46, P < 0.001). Ear-lobe capillary blood ammonia thus accurately reflects arterial ammonia and is an attractive alternative. The higher fingertip ammonia may be due to contamination with ammonia-rich sweat from finger grooves, regardless of the precautions taken.