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Biliary Diversion by Use of the Appendix (Cholecystoappendicostomy) in Progressive Familial Intrahepatic Cholestasis

1999; Lippincott Williams & Wilkins; Volume: 28; Issue: 2 Linguagem: Inglês

10.1097/00005176-199902000-00026

1536-4801

Winfried Rebhandl, Franz X. Felberbauer, Julia R. Turnbull, Kurosh Paya, Ulrich Barcik, W. Huber, Peter F. Whitington, Ernst Horcher,

Clinical Nutrition and Gastroenterology

Progressive familial intrahepatic cholestasis is among the five most common indications for orthotopic liver transplantation in children (1). The disease develops early in childhood as unremitting cholestasis without identifiable infectious, metabolic, or anatomic causes. Analysis of liver biopsy specimens is unspecific (2), but there is a typical pattern of laboratory findings in serum, especially low to normal level of γ-glutamyl transpeptidase (GGT), absent lipoprotein X, low cholesterol level, and high levels of bile acids (3). Recently, the responsible loci have been mapped in Amish (4) and Middle Eastern families (5), and a genetic diagnosis may therefore be possible in the near future. Bile acids seem to be the cause of hepatocellular injury (5) resulting in end-stage cirrhosis. Severe pruritus is another hallmark of the disease. Therefore, removal of abundant bile salts and other components of bile responsible for the pruritus is one of the principal intentions of therapy (6). Available medical approaches were ineffective in interrupting the fatal progression of the disease and in alleviating the pruritus (7). A surgical approach has become the therapy of choice. External diversion of bile by use of a 10-cm jejunal segment interposed between the fundus of the gallbladder and the abdominal skin partly interrupts the enterohepatic recirculation of bile salts (1,6). A success rate of 75% (delay or even reversion of hepatic injury) has been reported in patients who did not have cirrhosis at the time of surgery (1). However, even those patients in whom orthotopic liver transplantation cannot be avoided benefit, because the agonizing pruritus usually resolves and time is won until transplantation. As an alternative to the use of a small bowel segment, we report a case of successful biliary diversion by performing a cholecystoappendicocutaneostomy. CASE REPORT Patient's Data M. B. was a full-term (3420 g) Turkish boy who was the product of an uncomplicated pregnancy. His grandparents were consanguineous. From the third week of life, progressive jaundice developed. There was no indication of viral or autoimmune hepatitis. Analysis of specimens obtained in repeated biopsies showed severe ductal cholestasis and progressive biliary fibrosis. The boy was referred to the University Clinics of Pediatrics at the age of 10 years. Surgery was performed at 13 years because of deteriorating liver function parameters and itching that was refractive to therapy. On physical examination we noted jaundice, a remarkably thickened skin with mutilations, hemorrhage, and scarring, paw-like hands and short stature (below the 3rd percentile for Turkish boys). The face was characteristic as well: pointed chin, broad forehead, and fleshy ears. There was no mental retardation. Some serum values were slightly elevated: 27 U/l alanine aminotransferase, 37 U/l aspartate aminotransferase, and 5 mg/dl total and 3.4 mg/dl conjugated bilirubin; whereas others were normal: 13 U/l γ-glutamyl transpeptidase and 186 mg/dl cholesterol. Serum bile acids at 498 µmol/l were markedly elevated, whereas lipoprotein X was completely absent. Operative Procedure A pre-existing midline upper abdominal incision was used (an emergency laparotomy had been necessary after a liver biopsy at 2 years of age). On inspection, the liver was indurated, slightly enlarged, with sharp margins and a smooth surface. The gallbladder appeared unusually large but without signs of inflammation. The appendix, 10 cm long, was found lateral to the cecum, and a tension-free anastomosis between these organs therefore appeared feasible. The appendix was detached from the cecum, and the mesoappendix was mobilized to secure blood supply. The tip of the appendix was then amputated and the lumen calibrated. The base was brought up behind the cecum into the subhepatic area and anastomosed with the fundus of the gallbladder (Fig. 1). A "nipple" stoma was thereafter matured in the right lower abdominal quadrant. A 10 French catheter was placed as a stent in the appendicular conduit.FIG 1: The anastomosis of the appendix (2) to gallbladder (1) and abdominal wall (3).Results The pruritus (grade 4 + according to the scale of Whitington and Whitington [6]), which had been refractive to medical therapy, resolved completely (grade 0+) within 3 weeks. Fluid output through the stoma approximated 1200 ml/day immediately after surgery. Four weeks after the operation, it had increased to approximately 3000 ml/day so that intravenous fluid substitution for 3 days became necessary. Afterward, stomal output decreased again and is now between 600 ml and 1200 ml/day. Elevated liver function parameters have returned to normal. Serum bile acids reached a baseline of approximately 60 µmol/l after 2 months and vary now at approximately 150 µmol/l. Two complications were seen: a retraction of the nipple on the 14th postoperative day and a subcutaneous abscess near the stoma a few weeks later. The stent was removed after 2 months, and the conduit worked well thereafter. Twenty-four months after surgery the boy who had needed tutoring because of lengthy hospitalizations was able to attend a regular school. He copes with the stoma completely on his own, and he is able to regulate fluid intake in accordance with stomal output. DISCUSSION Defective primary bile acid secretion seems to be the underlying pathogenetic mechanism in Byler disease (8). No known medical therapy has been successful in lowering levels of bile salts; surgery, ideally performed early in life, is therefore the treatment of choice. Numerous procedures have been proposed for biliary diversion, but the jejunal conduit has more or less emerged as a standard approach because of several advantages (3). First, the stoma can be positioned below the belt line in the right lower quadrant. Second, the properistaltic function of the jejunum prevents reflux of contaminated bile from the external stoma into the biliary tree and thus reduces the risk of cholangitis (1). Although theoretically a direct anastomosis between the gallbladder and the skin (cholecystostomy) provides the most direct method of external diversion, there are several disadvantages that have been discussed in detail (3). Recently, ileal exclusion has been proposed as a stoma-free biliary diversion (9) in these patients, but this procedure has also been questioned because of persistent chologenic diarrhea (3) and because the long-term results remain uncertain. In 1980, Mitrofanoff (10) described the use of the appendix as a continent vesicostomy. He created a channel for a catheter between the abdominal wall and the urinary bladder. This urologic technique of a tunneled, nonrefluxing anastomosis has been adapted for biliary appendicoduodenostomy (11) and hepaticoportoappendicostomy in biliary atresia (12). We think that in selected cases a modified Mitrofanoff procedure may be applied for drainage of the gallbladder in Byler disease. The appendix provides an epithelialized, vascularized, isoperistaltic conduit with a smaller diameter than the jejunum. The appendix can be isolated more easily than the jejunum. A jejunal anastomosis with its potential complications is avoided, and the procedure interferes less with impending orthotopic liver transplantation (in which a Roux-en-Y choledochojejunostomy is often required). Although the lumen of the appendix is smaller than the diameter of the jejunum, cholangitis caused by possibly inadequate decompression has not been observed in our patient during the past 26 months. Peristalsis has been shown to propagate from the cecal end to the tip (13). Therefore, the appendix was interposed with its cecal end to the gallbladder and its tip to the abdominal wall. Preservation of the blood supply is critical to the success of the procedure. Rotation and tension at the mucocutaneous anastomosis should be avoided. Of course, this procedure can only be performed if the appendix is of appropriate length. We have learned that preparation of an adequate nipple is crucial: In our case, the nipple unfortunately retracted approximately 2 weeks after surgery. Several months after we had performed this operation, a report by Gauderer and Boyle (14) appeared describing a successful cholecystoappendicostomy in a child with Alagille syndrome. It was interesting to learn that their conclusions mainly support our views. Although our patient had a clear benefit from surgery because the pruritus he had had all his life was entirely and promptly resolved, the outcome was not completely satisfactory. Bile acids should have returned to normal levels. We ascribe this to the fact that he was referred to surgical therapy relatively late; a biopsy specimen obtained shortly before the operation showed the signs of already severe fibrosis. More than a liter of bile daily, although manageable, is a considerable loss of fluid in a child, and increased choleresis is a well-known sign of liver cirrhosis and ductular proliferation (15). However, his liver function, according to the results of biochemical tests, has remained stable since the operation, and progression to cirrhosis has at least been delayed. CONCLUSION As long as there is no specific medical therapy, surgery is the treatment of choice for progressive familial intrahepatic cholestasis. We hope that the use of the appendix for biliary diversion will extend the surgeon's ability to deal effectively with this disease.