David A. Burnett

Shunt surgery versus endoscopic sclerotherapy for long-term treatment of variceal bleeding. Early results of a randomized trial

In September 1982, a prospective randomized trial comparing shunt surgery and endoscopic sclerotherapy for the elective management of variceal hemorrhage in patients with cirrhosis was initiated. Twenty-seven patients have received shunts (distal splenorenal = 23, nonselective = 4) and 30 patients have had chronic sclerotherapy. Eighty-six per cent of patients had alcoholic cirrhosis and 33% were Childs class C. After a mean follow-up of 25 months, 19% of shunt and 57% of sclerotherapy patients have had rebleeding (p = 0.003). Kaplan-Meier survival analysis reveals similar 2-year survival rates for shunt (65%) and sclerotherapy (61%) groups. Only two of 10 sclerotherapy failures have been salvaged by surgery. Posttherapy quantitative hepatic function, frequency of encephalopathy, and cumulative medical costs were similar for both groups. Hepatic portal perfusion and portal pressure at 1 year were better maintained by sclerotherapy than by distal splenorenal shunt. In conclusion, endoscopic sclerotherapy and shunt surgery provide similar results with respect to survival, hepatic function, frequency of encephalopathy, and costs. Sclerotherapy is an acceptable, but not superior, alternative to shunt surgery for treatment of variceal hemorrhage.

Distal spleno-renal shunt versus endoscopic sclerotherapy in the prevention of variceal rebleeding A meta-analysis of 4 randomized clinical trials

Meta-analysis was used to evaluate 4 clinical trials comparing distal spleno-renal shunt (DSRS) with endoscopic sclerotherapy (EVS) in the prevention of variceal rebleeding: the interval between bleeding and therapy ranges from < 14 days to > 100 days. A questionnaire was sent to each author of the published trials concerning methods, definitions and results of the trials in order to obtain more detailed and up-to-date information. The selected end-points for the meta-analysis were: rebleeding, mortality and chronic encephalopathy. Analysis of the results in the questionnaires was made using the method proposed by Collins. The pooled relative risk (i.e. the combined Odds ratio of each trial as an estimate of overall efficacy) of rebleeding was statistically reduced by DSRS (0.16; 95% confidence interval 0.10-0.27). Despite this, the overall risk of death following DSRS was only marginally decreased (0.78; 95% confidence interval 0.47-1.29); the lack of homogeneity in the results does not permit any significant conclusions on this end-point. However, in non-alcoholic patients, the decrease in risk of death was greater, and this without heterogeneity, following DSRS than EVS (0.59; 95% confidence interval 0.23-1.50). The overall risk of chronic encephalopathy was slightly increased after DSRS (1.86; 95% confidence interval 0.90-3.86). In conclusion, DSRS significantly reduced the risk of rebleeding compared to EVS without increasing the risk of chronic hepatic encephalopathy. However, DSRS did not significantly affect the overall death risk. Only in non-alcoholic disease did it seem to show an advantage over EVS.

Prothrombotic abnormalities in inflammatory bowel disease

Inflammatory bowel disease (IBD) is known to be associated with a thrombotic tendency, which is often attributed to thrombocytosis, elevated fibrinogen, or decreased antithrombin III. We prospectively studied eight patients with IBD, seven of whom had little or no disease activity, to determine if they had any laboratory abnormality known to be associated with an increased risk of thrombosis. Abnormalities in fibrinolysis were noted in five patients: four with high plasminogen activator inhibitor levels and one with poor release of tissue plasminogen activator following venous occlusion. Circulating immune complexes were present in the sera of five patients. Fibrinogen was mildly elevated in one patient, and two patients had mild thrombocytosis. Decreased levels of antithrombin III, protein C, or protein S were not observed. There appears to be a high incidence of abnormalities in fibrinolysis in inactive IBD, which may contribute to the high frequency of thrombosis seen in IBD. The presence of circulating immune complexes may contribute to vascular injury and thrombosis.

Shunt surgery versus endoscopic sclerotherapy for variceal hemorrhage: Late results of a randomized trial

Between September 1982 and April 1988, 60 cirrhotic patients with prior variceal hemorrhage were randomized to undergo the placement of an elective shunt (distal splenorenal: 26; nonselective: 4) or long-term endoscopic sclerotherapy (n = 30). Eighty-six percent of patients had alcoholic cirrhosis, and 33% were classified as Childs class C. After a mean follow-up of 87 months, 60% of patients undergoing sclerotherapy and 17% of shunt patients experienced rebleeding (p < 0.001). Shunt patients have survived longer than those who had sclerotherapy (6-year survival rates of 53% and 26%, respectively; p < 0.05). In part because of the wide geographic distribution of patients, only 4 of 13 patients in whom sclerotherapy failed (31%) could undergo salvage by shunt surgery. Although hepatic portal perfusion was better maintained after sclerotherapy, there were no major differences between the groups in terms of post-therapy hepatic or psychoneurologic function. In a predominantly alcoholic cirrhotic patient population (half non-urban), the results of elective shunt surgery were superior to those of chronic endoscopic sclerotherapy with respect to the prevention of recurrent variceal hemorrhage and survival.

Use of external shock-wave lithotripsy and adjuvant ursodiol for treatment of radiolucent gallstones: a national multicenter study

A prospective multicenter trial was performed to evaluate the use of external shockwave lithotripsy (ESL) and adjuvant medical therapy for the treatment of gallstones. A Medstone STS lithotripter was used together with ursodiol. Two hundred twenty-three patients were treated under general anesthesia (75%) or with intravenous analgesia (25%). Initial treatments were on an inpatient basis, but as centers gained experience, outpatient treatments became more common. Stone fragmentation and clearance were greatest in patients with solitary gallstones <2 cm in diameter. In this group of patients, stone fragmentation occurred in 97% of patients, and the cumulative stone-free rates at three and six months were 54% and 90%, respectively. These results indicate that fragmentation of gallstones can be achieved by a dry shock-wave lithotripter and that stone clearance is induced more rapidly by external shock-wave lithotripsy and adjuvant ursodiol therapy than by ursodiol therapy alone.

Radiographic demonstration of common bile duct varices.

Varicose veins may occur along the course of the common bile duct in patients with extrahepatic obstruction of the portal vein. These may cause partial biliary obstruction or excessive bleeding during biliary surgery. The cholangiographic appearance of choledochal varices is described.

Plasma postheparin diamine oxidase activity: development of a simple technique of assessing Crohn's disease

Plasma diamine oxidase (DAO) activity may reflect intestinal involvement in Crohns disease. The purpose of this study was to develop a simple heparin stimulation test for assessing postheparin plasma diamine oxidase activity in Crohns disease. Ten volunteers and five patients with Crohns disease received 1000 units and 3000 units of heparin intravenously and plasma samples were obtained at timed intervals. Plasma DAO activity increased significantly, compared with basal values, 30 minutes after 3000 units of heparin in both volunteers (26.2±5.0vs. 4.5±0.5 units/ml) and patients with Crohns disease (14.6±2.0vs. 4.0±1.1 units/ml,P<.05) and was significantly greater in the volunteers. There was no significant increase in DAO activity after 1000 units of heparin. Plasma DAO activity increased significantly within 15 minutes after 3000 units of heparin and remained at this high level at 60 minutes. Postheparin DAO activity correlated with the integrated area under the DAO activity curve. Plasma DAO activity correlated with the Crohns Disease Activity Index in the patients with Crohns disease. Plasma DAO activity, 30 minutes after the intravenous administration of 3000 units of heparin, should reflect intestinal involvement in Crohns disease.

Blood-group antigen expression during pancreatic cancer induction in hamsters

SummaryThe expression of blood group-related and tumor-associated antigens was examined in pancreatic adenocarcinomas and in the normal pancreas of hamsters to determine if this expression correlated with the host blood group and/or stage of carcinogenicity, respectively. Pancreatic tumors were induced by 4 weekly treatments of hamsters withN-nitrosobis(2-oxopropyl)amine (BOP) and analyzed immunohistochemically during different stages of tumor progression with polyclonal antibodies (PoAbs) and monoclonal antibodies (MoAbs) against A, B, O and Lewis (Le) isoantigens, including X, Y and CA 19-9 monosialoganglioside (gastrointestinal cancer antigen, GICA), as well as with PoAbs detecting human carcinoembryonic antigen (CEA), α-fetoprotein (AFP) and the Β-subunit of human chorionic gonadotropin (Β-HCG). The red blood cells of both control and tumor-bearing hamsters expressed AB and Le(a+b+)-like blood group types, as detected by polyvalent antisera. However, none of the MoAbs reacted with the hamster red blood cells. In the pancreas, all PoAbs against blood group antigens reacted with hyperplastic ducts and ductules at very early stages of carcinogenesis, as well as with neoplastic lesions, but not with normal pancreatic cells, except for the acinar cells, which were stained with PoAb-B, PoAb-Lea and PoAb-Leb. None of the MoAbs showed any affinity for the normal pancreatic cells; however, they reacted to various degrees with induced hyperplastic and neoplastic tissue. Reactivities of several MoAbs with malignant cells were greater than those with hyperplastic lesions: MoAb-B was highly reactive with all induced lesions, MoAb-A less reactive, and MoAb-H and MoAb-Ley (which has 6 sugar chains) detected only some cancer cells. Neither of the two MoAb-Lex (with 5 carbohydrate chains) reacted with carcinoma cells, although they did bind to a few hyperplastic cells. Neither MoAb-Lea and MoAb CA 19-9, nor PoAbs against CEA, AFP and Β-HCG, reacted with any normal, hyperplastic or malignant cells. These results demonstrate the differential reactivity of these PoAbs and MoAbs in normal and malignant pancreatic tissue and show that blood group antigens, especially the B isoantigens, are specific markers for induced pancreatic duct tumors in hamsters.

Nonoperative emergency treatment of variceal hemorrhage.

The nonoperative management of acute variceal hemorrhage can control acute hemorrhage and allow stabilization of the patient prior to definitive therapy to prevent further bleeding episodes. Balloon tamponade, endoscopic sclerotherapy, and pharmacotherapy can stop acute variceal bleeding. Endoscopic sclerotherapy has the highest reported success rate, decreases the incidence of early rebleeding, and is the recommended first method to control bleeding.

Presence of two distinct acinar cell populations in human pancreas based on their antigenicity

SummaryThe immunohistochemical localization of ABH- and Lewis (Le)-related blood group antigens, including CA 19-9, a sialylated Lea antigen, was examined using monoclonal antibodies (MoAbs) in 18 normal human pancreases and compared with ABH blood group antigenicity of the individuals. Acinar cells expressed ABH, Leb, Ley, and in some cases, Lex antigen in various proportions, but not Lea and CA 19-9. The reactivity of Leb and Ley was similar with regard to cellular localization and specificity. In all specimens but one, the distribution of Leb (and Ley) and H antigens on the one hand, and of A or B antigens on the other, showed a reciprocal relationship, in that one group of acini expressed Leb (and Ley) and H antigens, but lacked and A or B antigens (type 1 acinar cell); another group of acinar cells had A or B antigens, but expressed neither Leb (Ley) or H antigens (type 2 acinar cell). In ductal cells, four of eight individuals with blood group A, two of three with blood group B, and five of six with blood group O expressed the appropriate antigen, while the remainder did not. Lea antigen was expressed primarily by centroacinar and terminal ductular and ductal cells of medium-sized ducts of all specimens, whereas Leb was present in the cells of small and large ducts in all but four cases. The reactivity of ductal and ductular cells to Lex was negative, except for one case. MoAb-Ley and MoAb 19-9 reacted only with a few ductal cells in six (33%) and 12 cases (67%), respectively. There was no relationship in the expression of Le-related antigens between acinar and ductal/ductular cells; nor were there any sex difference with regard to the binding patterns of any antibodies. However, age appeared to influence the reactivity of some antibodies with acinar cells. Islet cells did not react with any of the antibodies. The results indicate that, although the antigenicity of epithelial cells can be affected by the host blood group types, there might be several regulatory systems for expression of blood group antigens in a cell-specific pattern.