Arthur J Geller

23.1. UPPER AND LOWER GASTROINTESTINAL ENDOSCOPY

In general, cancer must be ruled out in all patients awaiting organ transplantation. The endoscopist plays a definite role in this, especially in patients with end-stage liver disease. Upper gastrointestinal endoscopy is indicated in the preoperative evaluation of patients awaiting orthotopic liver transplantation. The rationale for performing this procedure in patients with advanced liver disease is to demonstrate the presence of lesions associated with portal hypertension, such as large esophageal varices, which may affect survival and may be treated with beta-blockers or band ligation.

The rationale for performing preoperative colonoscopy is to diagnose and to treat neoplastic lesions. If a cancer were diagnosed, curative resection, if possible, would be required prior to consideration of performing transplantation. Conversely, metastatic cancer is a contraindication to liver transplantation. Neither the underlying cause of the liver disease nor the Child-Pugh-Turcotte score apparently impacts the likelihood of finding a colon lesion. Thus, screening is carried out as it would be done in the general population, and patients older than 50 years should undergo screening examination of the colon. Preoperative colonoscopy should be performed in patients with primary sclerosing cholangitis and associated inflammatory bowel disease because of the increased risk of colonic dyspla-sia and cancer.

There are potentially increased risks in performing endoscopic procedures on patients who have advanced liver disease. Excessive bleeding may occur secondary to coagulopathy and to thrombocytopenia. Altered metabolism of sedative/ hypnotic medication may lead to oversedation and/or overt encephalopathy. Post-colonoscopy peritonitis in patients with ascites is another potential complication.

23.2. ROLE OF ENDOSCOPIC RETROGRADE CHOLANGIOGRAPHY (ERCP) IN LIVER TRANSPLANTATION

23.2.1. Preoperative Evaluation and Treatment

The endoscopic management of symptomatic dominant strictures in patients with primary sclerosing cholangitis includes balloon dilation and/or placement of a biliary endoprosthesis (stent). These interventions are successful in the majority of patients and have been demonstrated to delay the need for liver transplantation. In patients who are candidates for liver transplantation, endoscopic therapy of dominant strictures is clearly preferable to surgical reconstruction, because biliary surgery makes the subsequent transplant procedure more technically difficult. Endoscopic techniques used to demonstrate the presence of cholangiocarcinoma before transplantation include brush cytology and biopsy performed through the ERCP scope. Unfortunately, while the specificity is excellent, the sensitivity of these procedures is poor. Occult cholangiocarcinoma is thus found in the resected hepatectomy specimen in approximately 10% of transplants performed for endstage primary sclerosing cholangitis.

23.2.2. Postoperative Biliary Complications

Biliary complications may occur in up to one-third of liver transplant recipients. In the majority of adults undergoing liver transplantation, a choledocho-choledochostomy (CC) reconstruction is created in which there is a direct duct-to-duct anastomosis with or without a T tube. Conversely, in the vast majority of children, in all patients with primary sclerosing cholangitis, as well as a majority of those patients who require repeat transplantation, a choledochojejunostomy as Roux-en-Y (CJRY) is performed. The Roux limb varies typically between 20 and 40 cm of jejunum. This anatomy makes access to the anastomosis by ERCP difficult; therefore, a percutaneous transhepatic cholangiogram is usually required to evaluate biliary complications post-CJRY.

The risk of biliary complications posttransplant is increased in certain situations, including hepatic artery thrombosis, reduced-size grafts, prolonged allograft ischemia, and harvesting injuries. Hepatic artery thrombosis may occur in up to 10% of transplants in adults and a higher proportion in children. The donor common bile duct depends on the hepatic artery solely for its blood supply. Thus, bile duct ischemia is likely in the setting of hepatic artery thrombosis.

Reduced-size grafts are associated with a high frequency of biliary strictures. Possible causes for this association are prolonged ischemic time and chronic rejection. In itself, prolonged cold-ischemic time is associated with biliary complications such as stricture formation, epithelial sloughing, and biliary cast and sludge formation. The dissection performed during graft harvesting may compromise the blood supply to the proximal biliary tree of the donor liver in the absence of proximal hepatic artery obstruction. Portal vein thrombosis is also associated with a high frequency of biliary complications.

A donor cystic duct mucocele may develop as a result of continued mucous production in a segment of cystic duct ligated proximally and distally at a distance. The enlarging mass may cause a biliary obstruction in a manner analogous to Mirizzi's syndrome. The lesion may be demonstrated by ERCP but is not amenable to endoscopic therapy and requires surgery.

23.2.3. Management of Biliary Complications 23.2.3.1. Bile Leaks

Bile leaks (Fig. 23.1) are the most common type of biliary complication following liver transplantation. Multiple factors are believed to be responsible for the development of leaks in the early postoperative period. These early leaks are diagnosed in the initial hospitalization and typically occur at the anastomosis of a CC. The cause is related to poor healing, ischemia, and technical factors, such as tension on the anastomosis. Leakage at the T-tube insertion site may also occur early in the postoperative course. Other, less common causes are leaks related to the cut surface of a reduced-size graft, cystic duct leaks, and damage to accessory ducts. Leaks associated with the T tube typically occur approximately 4 months posttransplantation. The T tube is placed approximately 1 cm distal to the CC anastomosis on the contralateral side of the hepatic artery anastomosis. The routine use of T tubes has recently been called into question. Corticosteroids, used in the immunosuppressive protocol, are believed to play a role by inhibiting the formation of a mature fibrous tract, thus promoting the development of a leak.

Various endoscopic (ERCP) techniques have been employed in the management of bile leaks: sphincterotomy, nasobiliary tube placement, and endopros-thesis (stent) placement. In all of these therapies, the sphincter of Oddi pressure gradient is eliminated, equalizing the pressure in the common bile duct with that in the duodenum, and allowing bile to flow into the duodenum and away from the leak, permitting closure.

Bile Leak Ercp
Figure 23.1. ERCP image of a biliary leak with an associated anastomotic stenotic area.

Nasobiliary tube or stent placement without sphincterotomy is preferable because of the increased risks associated with sphincterotomy, such as bleeding, pancreatitis, and perforation. The advantage of the nasobiliary tube over the stent is the ability to perform interval cholangiograms easily and to remove the tube without a second endoscopic procedure. The majority of leaks (90%) can be successfully sealed with these techniques. The mean time to leak closure with the nasobiliary tube is approximately 5 days, with a range of 2-13 days. Stents have also been reported to treat leaks successfully after being left in place approximately 6-8 weeks.

23.2.3.2. Biliary Strictures

Postoperative biliary strictures (Fig. 23.2) may be classified as anastomotic or nonanastomotic. The pathogenesis of anastomotic strictures is related to technical factors as well as to local ischemia and fibrosis. Nonanastomotic strictures involve vascular and endothelial damage.

Hepatic artery thrombosis (HAT) is an important factor in the pathogenesis of strictures. Factors related to HAT include surgical technique, small vessel size, hypercoagulability, prolonged cold-ischemic time, and ABO blood group incompatibility. Immunologic injury may play a role in stricture formation. Patients with chronic ductopenic rejection and those transplanted with an ABO incompatible graft are at increased risk for the development of strictures. Patients who undergo transplantation because of primary sclerosing cholangitis are also at increased risk for the development of strictures.

Endoscopic management of biliary strictures is aimed at preventing complications of strictures such as choledocholithiasis, cholangitis, and biliary cirrhosis, while avoiding the need for surgery. Stricture dilation using balloon dilators is performed. Subsequently, stent placement is performed.

Bile Duct Stent Sizes

Nonanastomotic strictures (those involving the donor hepatic duct) are often associated with HAT, cholangitis, and choledocholithiasis, and are often multiple. These strictures are more difficult to treat and require more prolonged stenting. Rizk et al. (Gastrointest Endosc 1998;47:128-135), utilizing repeat ERCP and stent changes at 8- to 12-week intervals to prevent the complication of cholangitis secondary to stent occlusion, found that 22 months after the first ERCP procedure, 73% of patients with donor hepatic duct stricture were stent-free compared to 90% of patients with anastomotic stricture.

23.2.3.3. Bile Duct Dilatation

A mild increase of 1-2 mm in the caliber of the extrahepatic ducts has been reported posttransplantation. Biliary (Fig. 23.3) enlargement may be a benign finding or may indicate a pathological process. Sossenheimer et al. (Endoscopy 1996;25:565-571) have pointed out that although diffuse dilation of the bile duct is thought to be due to denervation of the native duct, normal sphincter of Oddi function has been demonstrated posttransplantation. Findings suggestive of obstruction are a larger duct caliber (> 12 mm), cystic duct remnant dilatation, and

Bile Duct Stent Complications
Figure 23.3. ERCP image of a benign biliary dilatation with stent placement.

abnormal liver enzymes. In this setting, a mechanical obstruction such as choledocholithiasis or sphincter of Oddi dysfunction (SOD) should be considered.

Liver enzyme improvement, with unclamping of the T tube, delayed contrast drainage on cholangiography, and delayed biliary drainage on hepatobiliary scin-tigraphy, supports the presence of an obstructive process. Performance of ERCP will rule out distal obstruction caused by stones, or distal strictures and sphincter of Oddi manometry may demonstrate SOD. Depending on the center and the allograft function, observation, endoscopic sphincterotomy, or CJRY may be performed for diffuse dilation of donor and recipient duct.

23.2.3.4. Choledocholithiasis and Biliary Sludge

Biliary calculi may be pigmented or cholesteric in nature. Predisposing factors are biliary obstruction, infection, and epithelial sloughing. Biliary sludge may be composed of unconjugated bilirubin or of casts of the duct comprising connective tissue and the lining wall of the bile duct. These are more common in cases of long-standing biliary obstruction or stenosis, HAT, prolonged cold preservation times (> 12 h), ABO-incompatible liver donors, or non-heart-beating liver donors. Endoscopic evaluation and treatment include ERCP to identify the debris and to assess for a predisposing obstructive lesion, such as a stricture. Endoscopic sphincterotomy and duct clearance are also performed at the time of ERCP to remove the debris. Alternatively, in the absence of HAT, CJRY reconstruction may be performed.

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