Endoscopic sclerotherapy plus propranolol versus propranolol alone in the primary prevention of bleeding in high risk cirrhotic patients with esophageal varices: a prospective multicenter randomized trial.

BACKGROUND: Analysis of primary prevention studies of the use of beta-blockers has shown clear reductions in variceal bleeding in cirrhotic patients with varices. In contrast, the usefulness of prophylactic endoscopic sclerotherapy, alone or in combination with propranolol, in the management of these patients is still under investigation. The present study compared the efficacy of combined sclerotherapy and propranolol versus propranolol alone in the primary prevention of hemorrhage in cirrhotic patients with varices and high (greater than 18 mm Hg) intraesophageal variceal pressure. METHODS: Patients were randomly assigned to propranolol (42 patients) or to propranolol plus sclerotherapy (44 patients). The mean duration of follow-up was 26.8 +/- 7.7 and 24.6 +/- 9.8 months, respectively. RESULTS: During this period 23% of the patients in the combination group experienced at least 1 episode of bleeding due to varices or congestive gastropathy as compared with 14% in the propranolol group (not significant). Twenty-three patients (52%) in the combination group developed complications as compared with 8 (19%) in the propranolol group (p = 0.002). The mortality rate was similar in both groups (14% and 18%, respectively). The only independent factor predictive of survival was the level of serum albumin. CONCLUSIONS: Endoscopic sclerotherapy should not be used for the primary prevention of hemorrhage in cirrhotic patients at high risk of variceal bleeding who are undergoing treatment with propranolol.

Endoscopic sclerotherapy versus variceal ligation in the long-term management of patients with cirrhosis after variceal bleeding. A prospective randomized study.

BACKGROUND/AIMS: Long-term endoscopic injection sclerotherapy of oesophageal varices prevents rebleeding in patients with cirrhosis surviving an acute variceal bleeding episode. However, this treatment is associated with a substantial complication rate. Endoscopic band ligation is a newly developed technique in an attempt to provide a safer alternative. The aim of this study was to compare the efficacy and safety of injection sclerotherapy versus variceal ligation in the management of patients with cirrhosis after variceal haemorrhage. METHODS: Seventy-seven patients with cirrhosis who proved to have oesophageal variceal bleeding were studied. After initial control of haemorrhage by sclerotherapy, 40 of the patients were randomly assigned to sclerotherapy and 37 to ligation. Both procedures were performed under midazolam sedation at intervals of 7-14 days until all varices in the distal oesophagus were eradicated or were too small to receive further treatment. RESULTS: The eradication of varices required a lower mean number of sessions with ligation (3.7 +/- 1.9) than with sclerotherapy (5.8 +/- 2.7, p = 0.002). The mean duration of follow-up was similar in both groups (15.6 months +/- 7.3 and 15 +/- 7.4, respectively). The proportion of patients remaining free from recurrent bleeding against time was significantly higher in the ligation group as compared to the sclerotherapy group (chi 2 = 3.86, p = 0.05). Only 13 patients (35%) developed complications in the ligation group as compared to 24 (60%, p = 0.05) in the sclerotherapy group. The mortality rate was similar in both groups (20% and 21%, respectively). CONCLUSIONS: Variceal ligation is better than sclerotherapy in the long-term management of patients with cirrhosis after variceal haemorrhage which was initially controlled with sclerotherapy.

Urinary gastrin output and serum gastrin in patients with liver cirrhosis. Urinary gastrin output in cirrhosis.

The aim of the present study was to examine the diurnal urinary gastrin output in cirrhotics and to clarify whether in patients with hepatorenal syndrome urinary gastrin output is reduced. Thirty-two cirrhotics and 25 age- and sex-matched, controls were studied. Cirrhotics were divided into 3 groups: (I: without ascites and normal serum creatinine; II: ascites and normal creatinine; III: ascites and increased creatinine). Mean fasting serum gastrin concentration was lower in the control group than in Group I, II (p < 0.01) or III (p < 0.001). In this latter group mean serum gastrin concentration was significantly higher (p < 0.001) than in the other two groups of cirrhotics. The mean 24 h urinary gastrin output was lower (p < 0.001) in Group III patients than in the other groups of subjects studied. Also in the controls urinary gastrin output was lower (p < 0.01) than in Groups I and II. These findings suggest that: a) in cirrhotics with normal serum creatinine the average serum gastrin levels over the course of the day are indeed higher than in normals and b) In cirrhotics with hepatorenal syndrome, impaired urinary gastrin output appears to contribute significantly to their hypergastrinemia.

Propranolol in the prevention of recurrent upper gastrointestinal bleeding in patients with cirrhosis undergoing endoscopic sclerotherapy. A randomized controlled trial.

The purpose of this study was to investigate the possible value of continuous administration of propranolol in the prevention of recurrent upper gastrointestinal bleeding in patients with cirrhosis undergoing chronic endoscopic sclerotherapy. Among 239 patients admitted for acute variceal bleeding, 85 with cirrhosis were randomized to receive sclerotherapy either alone (40) or in combination with propranolol (45). Sclerotherapy was carried out with an intravariceal injection of 5% ethanolamine oleate through a fiberoptic endoscope. The procedure was performed every week, until the esophageal varices at the gastroesophageal junction were too small for any further injections. Varices were reinjected if they recurred. Propranolol was given orally twice a day until heart rate was reduced by 25% in the resting position. The mean follow-up period was 23.2 and 24.2 months for sclerotherapy and the sclerotherapy plus propranolol groups, respectively. During this period a significant (P = 0.001) reduction in the recurrence of esophageal varices was observed in patients treated with the combination of sclerotherapy plus propranolol compared with those treated with sclerotherapy alone. However, the time of rebleeding from any source or from esophageal varices did not differ significantly between the two groups. In the sclerotherapy group 21 patients rebled (35 bleeding episodes) compared with 14 (22 episodes) in the combination therapy group. Patients in the sclerotherapy group were more prone to bleed from gastric varices and congestive gastropathy than patients treated with the combination of sclerotherapy plus propranolol (P = 0.012). Twenty-five patients in the endoscopic sclerotherapy group developed complications attributed to sclerotherapy compared with 23 patients in the sclerotherapy plus propranolol group. Complications directly attributable to propranolol were observed in 11 patients. Three of these patients stopped taking the drug due to heart failure (1) and flapping tremor (2). Eight patients (17.8%) died in the latter group while the corresponding figure in the sclerotherapy group was nine (22.5%). It is concluded that the continuous administration of propranolol may reduce incidences of recurrent upper gastrointestinal hemorrhage from gastric sources in patients with cirrhosis undergoing chronic sclerotherapy.

A prospective randomized trial comparing somatostatin, balloon tamponade and the combination of both methods in the management of acute variceal haemorrhage.

The aim of this study was to compare the efficacy of: (i) somatostatin infusion, (ii) balloon tamponade with the Sengstaken-Blakemore tube and (iii) the combination of both methods, in the management of acute variceal haemorrhage. Ninety-two consecutive patients with liver cirrhosis who proved to have active variceal bleeding on emergency endoscopy were studied. Thirty-one patients were randomly assigned to an intravenous infusion of 250 micrograms/h of somatostatin (Group I), 30 to the Sengstaken-Blakemore tube (Group II) and 31 to the combination of both methods (Group III). Somatostatin was administered for 24 h, while the gastric and esophageal balloons remained inflated for 48 and 24 h, respectively, then deflated. Patients were under observation for a further 24-h period after withdrawal of treatment. If bleeding recurred, the same treatment was repeated in each group. Following treatment the bleeding was controlled initially in 22 patients (71%) in Group I, in 24 (80%) in Group II and in 25 (80.6%) in Group III. In Group II a significantly (p less than 0.05) higher proportion of patients (14/24) rebled as compared to Groups I (5/22) and III (6/25). Bleeding was controlled following retreatment in four, ten and five patients of the three respective groups. There were marked differences, in the number of complications noticed with each form of therapy. Only three patients (9.7%) in Group I developed complications (p less than 0.05) as compared to ten (33%) in Group II and ten (32%) in Group III. Hospital mortality in all three treatment groups was not significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)

Duodenogastric reflux before and after surgical or medical therapy for duodenal ulcer.

Duodenogastric reflux was studied in 48 duodenal ulcer patients before and after medical (n = 8) or surgical therapy with either combined truncal vagotomy and gastrojejunostomy (n = 13) or pyloroplasty (n = 12), Polya partial gastrectomy (n = 8), or highly selective vagotomy (n = 7). Seven healthy subjects served as controls. The reflux was assessed both by using 99mTc diethyliminodiacetic acid (HIDA) scintigraphy and by measuring intragastric bile acid levels following endoscopic gastric juice aspiration. Before therapy, duodenal ulcer patients had significantly higher intragastric bile acid concentrations than did normal subjects (p less than 0.001). After truncal vagotomy and drainage, or partial gastrectomy, bile acid levels increased significantly, whereas they remained unchanged after medical therapy. Conversely, they were found to be significantly decreased after highly selective vagotomy. The results of HIDA scan measurements were compatible with those of gastric juice bile acids. We conclude that surgical treatment for duodenal ulcer by highly selective vagotomy is the only form of therapy, among the types considered, that leads to a reduction in duodenogastric reflux. It is of interest that medical therapy of the duodenal ulcer does not improve abnormal duodenogastric reflux, possibly contributing to both the failure of the medical treatment and recurrence of the ulcer.

A comparative trial of 400 mg cimetidine twice daily and 1000 mg daily in the short-term treatment of duodenal ulceration.

The therapeutic efficacy of cimetidine given as 400 mg twice daily was compared to that of cimetidine given as 1.0 g daily in 4 divided doses (200 mg 3-times daily and 400 mg at night) in two groups of 25 patients (total 50 patients) with active duodenal ulceration. After 4 weeks, healing rates of 72% and 76%, respectively, were observed for the two dosage regimens. Patients who remained unhealed at 4 weeks were treated for a further 4 weeks, after which cumulative healing rates of 84% and 92%, respectively, were obtained. None of the observed differences in healing rates were statistically significant. Symptomatic improvement was similar for the two dosage regimens. No significant adverse reactions were reported.

Bowel preparation and the risk of explosion during colonoscopic polypectomy.

Concentration of oxygen, methane, and hydrogen were measured in intracolonic gas samples aspirated through the colonoscope at the time of colonoscopy from 46 patients. Of the above patients 20 prepared either with mannitol (n = 10) or with castor oil (n = 10) had the instrument passed to the caecum without air insufflation or suction. After mannitol, mean intracolonic hydrogen concentration (4.07%) was significantly higher (p less than 0.001) than after castor oil (0.51%). Mean oxygen and methane concentrations were approximately similar. Potentially explosive concentrations of hydrogen (greater than 4.1%) and or methane (greater than 5%) were present in 6/10 patients given mannitol and 2/10 patients given castor oil. Nevertheless only one patient from each group had coexisting oxygen concentrations of more than 5% producing thus a combustile mixture. Routine colonoscopy (using air insufflation and suction) was performed in 26 patients prepared with mannitol. Mean intracolonic hydrogen and methane was 0.63% and 0.88% respectively. The highest recorded concentration of hydrogen was 2.6%, and of methane 2.1%, while all patients had oxygen concentrations of more than 5%. It is suggested, therefore, that routine insufflation and suction before colonoscopic electrosurgical polypectomy should result in safe levels of these gases. The remote possibility of pockets of undiluted gas in explosive concentration, however, indicates the use of an inert gas such as carbon dioxide if mannitol preparation is used before electrosurgery.

Plasma lipoprotein pattern in relation to liver histology after toxic hepatitis and experimental biliary obstruction in rabbits.

Plasma lipoproteins were studied in relation to liver histology in rabbits in the course of toxic hepatitis and compared to those after experimental biliary obstruction. The lipoprotein electrophoretic pattern became deeply abnormal during the acute phase of toxic hepatitis and correlated with the degree of liver injury, improving during recovery. Liver damage was more severe after carbon tetrachloride than after alcohol and milder after allylo-isopropyl-acetamide, a porphyrinogenic substance. Lipoprotein abnormalities were not followed by significantly reduced levels of cholesterol esters in the plasma. In comparison, animals with biliary obstruction developed milder liver damage presented gross abnormalities of plasma lipids and lipoproteins, followed by relative deficiency of cholesterol esterification. It is concluded that lipoprotein changes in acute liver injury, although non-specific, are a sensitive index of liver damage and recovery. Serious acute liver injury can exist without significant fall in cholesterol esters.