D. Westaby

Randomised trial of variceal banding ligation versus injection sclerotherapy for bleeding oesophageal varices

Injection sclerotherapy of bleeding oesophageal varices is undoubtedly beneficial but it is associated with a substantial complication rate, and variceal rebleeding is common during the treatment period before variceal obliteration is achieved. We aimed to find out whether endoscopic variceal banding ligation is safer and more effective. The two methods were compared in a randomised controlled trial of 103 patients (54 assigned to banding ligation, and 49 to injection sclerotherapy) of whom 21 (39%) and 23 (47%), respectively, had active bleeding at index endoscopy. Both treatments were highly effective in controlling active haemorrhage (91% and 92% respectively). Variceal obliteration was not achieved for 22 patients in each group, but among those whose varices were eradicated, banding ligation achieved obliteration more quickly than did sclerotherapy (mean 39 [SD 4] vs 72 [7] days, p = 0.004) and in fewer endoscopy sessions (3.4 [2.2] vs 4.9 [3.5], p = 0.006). Rebleeding was less common in the banding ligation group than in the sclerotherapy group (16 [30%] vs 26 [53%], p < 0.05). There was no difference in outcome between the groups, but 14 sclerotherapy patients were withdrawn from the trial (7 for orthotopic liver transplantation) compared with only 5 (1 for liver transplantation) in the banding ligation group (p < 0.05). Complication rates were similar in the two groups. Variceal banding ligation is a safe and effective technique, which obliterates varices more quickly and with a lower rebleeding rate than injection sclerotherapy.

INCREASED LONG-TERM SURVIVAL IN VARICEAL HAEMORRHAGE USING INJECTION SCLEROTHERAPY: Results of a Controlled Trial

Analysis of 107 patients with cirrhosis and recent variceal haemorrhage included in a prospective randomised trial of endoscopic injection sclerotherapy showed that in the sclerotherapy group 22 (43%) of the 51 patients had episodes of haemorrhage during the period of treatment, but in only 4 did bleeding occur after the varices had been obliterated. This contrasts with episodes of bleeding in 42 (75%) of the 56 patients receiving standard medical management-a highly significant difference. The overall risk of bleeding per patient-month of follow-up was reduced threefold with sclerotherapy. Of 22 patients followed up for at least one year after obliteration of varices, 14 had no evidence of reappearance of varices within this period and, by means of cumulative life-analysis tables, survival was shown to be significantly improved in the sclerotherapy group.

PROSPECTIVE CONTROLLED TRIAL OF INJECTION SCLEROTHERAPY IN PATIENTS WITH CIRRHOSIS AND RECENT VARICEAL HÆMORRHAGE

64 patients with cirrhosis and recent variceal haemorrhage were studied in a prospective randomised trial of injection sclerotherapy by means of a flexible oesophageal sheath. 12 (33%) of the 36 patients in the sclerotherapy group, suffered further bleeds from varices compared with 19 (68%) of the 28 patients receiving standard medical treatment. The risk of bleeding per patient-month of follow up decreased more than threefold with sclerotherapy and the number of patients rebleeding after 2, 6, and 12 months was significantly reduced (p < 0.05). 1-year survival without further bleeding improved significantly with sclerotherapy (46% compared with 6%, p < 0.02), although the difference in overall survival assessed by cumulative life-table analysis was not statistically significant. The main complication of the technique was the development of oesophageal ulcers in some patients.

LIVER DISEASE AND BILEDUCT ABNORMALITIES IN ADULTS WITH CYSTIC FIBROSIS

A quarter of adults with cystic fibrosis, 57 of 233, had abnormal liver function. Patients with hepatic dysfunction were further investigated by ultrasound, hepatobiliary scintigraphy, and endoscopic retrograde cholangiography (ERC). 17 of the 23 patients studied had abnormalities on imaging. All 15 patients who underwent ERC had abnormal intrahepatic ducts, but only 2 had stricture of the common bile duct. These findings suggest that, in patients with cystic fibrosis, intrahepatic impairment of biliary drainage may be important in the pathogenesis of liver disease.

Endoscopic sclerotherapy in the management of gastric variceal haemorrhage

The value of injection sclerotherapy in the management of active gastric variceal bleeding is unclear. A retrospective study was therefore performed of 46 episodes of acute variceal haemorrhage in 41 patients who were treated by endoscopic sclerotherapy. The site of gastric variceal haemorrhage was the lesser curve (Group 1) in 13, within a hiatus hernia (Group 2) in six, and fundal with or without associated oesophageal varices (Type 3) in 22 cases. Haemostasis was achieved by sclerotherapy in 54%, 71.4% and 26%, respectively. After additional measures including balloon tamponade or surgery 85% of the Group 1 cases had stopped bleeding significantly more frequently than was observed in Group 3 (44.4%). More patients in Group 3 died due to uncontrolled bleeding (41%) than in Group I (7.7%). Hospital mortality depended on the severity of the liver disease with 15% of Childs grade A and 56% of grade C cases dying. It is concluded that endoscopic sclerotherapy of gastric varices should be reserved only for lesser curve or hiatal varices and that early surgery (or sclerotherapy using tissue adhesive) be considered for variceal haemorrhage originating from fundal varices.

Androgen Related Primary Hepatic Tumors in Non-Fanconi Patients

Three cases of androgen related primary hepatic tumor in non‐Fanconi patients are described in whom detailed information is available concerning histologic changes and clinical course over long periods. Two patients presented with hepatic rupture and hemoperitoneum requiring surgical intervention. In one case histologic assessment showed a hepatic adenoma which has almost completely regressed over four years since androgen withdrawal. In two patients there was a degree of nuclear pleomorphism not seen in ‘spontaneous’ adenomas and following androgen withdrawal there has been no evidence of progression or of metastases although the tumor has not regressed over a follow‐up period of two years.

Primary amyloidosis and severe intrahepatic cholestatic jaundice.

Liver involvement in systemic amyloidosis is frequent but is rarely of clinical importance. Five patients with severe cholestatic jaundice are described and an additional 20 from published reports are reviewed. The most frequent presenting symptoms were lethargy and abdominal pain, which were present for a median of 11 months before the onset of jaundice. Hepatomegaly, usually marked, was present in 92%, with ascites in 56% of the cases. The serum bilirubin concentration was noticeably high and the serum globulin low. Histology of the liver showed considerable perisinusoidal deposition with a slight predilection for the periportal area. Two patients presented with predominant centrilobular deposition. Congo red staining was not uniformly positive. A variety of treatment regimens was tried but median survival was only three months from the onset of jaundice.

Management of common bile duct stones with a biliary endoprosthesis. Report on 40 cases.

Endoscopic placement of a biliary endoprosthesis has been proposed for the management of choledocholithiasis when stone extraction is difficult or considered hazardous. Over a two year period this approach was used in 40 such patients. There were 24 women and 16 men with a median age of 76 years. In seven patients with severe cholangitis no attempt was made to extract the stones. Twenty three (57.5%) patients underwent a sphincterotomy and four (10%) needle knife papillotomy. The endoprosthesis insertion was considered a temporary measure in 13 (32.5%) patients and definitive treatment in 27 (67.5%). Bile duct drainage was established in all patients. Early complications occurred in six patients (15%), but were without sequelae. Late complications developed in eight (20%) of the patients and included biliary colic (four), cholangitis (three), and cholecystitis (one). Two patients (one cholangitis and one cholecystitis) died as a consequence of the complication. Only patients without a sphincterotomy developed cholangitis. A total of eight patients (20%) underwent surgery (one as an emergency) and nine a repeat endoscopic retrograde cholangio pancreatography (two as an emergency) to clear the duct. The remaining 23 patients are asymptomatic at a median of 13 months (range five to 24 months). Biliary endoprosthesis insertion for choledocholithiasis is an important alternative means of establishing drainage in selected cases, and is probably the optimum method of management for the elderly and or debilitated patients with previous cholecystectomy. Caution must be exercised, however, in patients with an in situ gall bladder.

Effect and mechanism of action of isosorbide-5-mononitrate.

Nitrates have been shown to decrease portal pressure in cirrhotic patients with portal hypertension and this has been attributed to decreased portal venous resistance. We studied the effect and mechanism of action of oral administration of isosorbide-5-mononitrate (Is-5-Mn) (20 mg), which, unlike the dinitrate, does not require hepatic biotransformation to a vasoactive metabolite on portal and systemic haemodynamics in 11 patients with portal hypertension complicating cirrhosis. A significant reduction in portal pressure gradient (WHVP-FHVP) (from 23.9 (3.4) to 21.8 (3.4) mmHg: p less than 0.005) occurred 60 minutes after Is-5-Mn due entirely to a fall in WHVP, associated with decreased estimated liver blood flow (from 1940 (159) to 1639 (179) ml/min: p less than 0.05). Right atrial and pulmonary artery pressures and cardiac index fell significantly whilst mean arterial pressure remained unaffected. Heart rate and the calculated systemic vascular resistance index increased significantly. Significant correlations existed between the reduction in portal pressure gradient and fall in cardiac index (r = 0.65, p less than 0.05) and increase in systemic vascular resistance index (r = 0.72, p less than 0.02). The observed decrease in estimated liver blood flow, in association with an increase in systemic vascular resistance index, suggests that baroreceptor mediated splanchnic vasoconstriction may be one of the factors responsible for the fall in portal pressure, rather than portal venous dilatation.

Pathophysiology of Portal Hypertension

Portal hypertension is characterised by alterations in the splanchnic and systemic circulation associated with the development of portosystemic collateral channels, the most important of which are found in lower oesophagus and stomach. Bleeding from these gastro-oesophageal varices represents the major clinical complication and over the last decade there has been considerable interest in the pharmacological management of this condition. The factors underlying the development and maintenance of portal hypertension and the pathogenesis of variceal rupture are as yet not fully understood. Whilst an increase in portal vascular resistance, as a consequence of liver disease, appears to be the primary event in the majority of cases, increasing attention has focused on the potential importance of enhanced circulating levels of vasoactive compounds coupled with a proposed reduction in vascular sensitivity to endogenous vasoconstrictors. Consequently, portal hypertension is now being more widely considered as a multi-organ disorder associated with changes in blood flow within both systemic and splanchnic vascular beds. This article reviews the factors currently implicated in the development and maintenance of portal hypertension and considers the pathogenesis of variceal bleeding.