Reduction of Morbidity and Mortality from Biliary Complications after Liver Transplantation s. KLEIN,' SCOTT SAVADER,' JAMES F. BURDICK,'JEFFREY FAIR,^ MACK MITCHELL,3 PAULCOLOMBANI,' BRUCEPERLER,~ FLOYD OSTERMAN' AND G. MELVILLE WILLIAMS^
From the Departments of 'Surgery, 2Radiology and 3Medicine, The Johns Hopkins Hospital, Baltimore, Maryland 21205
favor of choledochocholedochostomy or Row-en-Y choledochojejunostomy has dramatically decreased the incidence of postoperative biliary complications (3,4). The use of monofilament and absorbable suture material for biliary reconstruction has recently been shown to reduce further the incidence of anastomotic complications (5). Nevertheless, biliary tract complications remain a not infrequent cause of posttransplant morbidity and mortality (16.6% and 9.6%, respectively, in a recent large series) (4). Bile duct stricture, obstruction and leak account for most biliary complications, and the traditional approach to these problems has often necessitated reoperative surgery. Several institutions have reported successful treatment of these complications by percutaneous transhepatic cholangiography with drainage, dilatation and/or stenting (6-8).Endoscopic retrograde cholangiography with stenting, biliary drainage or both have also been useful in managing selected patients (9, 10). We report a series of 91 consecutive orthotopic liver transplant patients, six of whom developed postoperative biliary complications. Three patients had biliary stricture, one patient had bile duct obstruction after Over the last 27 years, orthotopic liver transplan- percutaneous biopsy-related hemobilia and one patient tation has evolved from an experimental operation with had biloma formation. In one patient the distal portion limited short-term survival to a well-accepted surgical of the T tube could not be dislodged from the intraabtherapy for selected patients with end-stage liver dominal and subcutaneous tract when removal was disease. The improved patient survival to its present attempted routinely at 4 mo. He required a surgical level of 70% to 85% (1) is attributable to advances in exploration to locate and extract the T-tube remnant. preoperative patient selection and preparation, surgical The other five patients were managed nonoperatively technique and intraoperative management, immuno- with the interventional radiology techniques described suppressive protocols and postoperative care. A sig- below. nificant incidence of morbidity and mortality after liver SUBJECTS AND METHODS transplantation has been attributed to biliary tract Between October 1986 and August 1990, 103 orthotopic complications. Early series in which the gallbladder was liver transplants were performed at the Johns Hopkins used as a conduit for biliary drainage to the duodenum or jejunum reported a 34% incidence of biliary ob- Hospital. Of the 91 patients transplanted, 81 were adults and struction or fistula formation (2). Abandonment of the 10 were children. The standard technique of orthotopic liver transplantation as described elsewhere (11)was used. Biliary cholecystoduodenostomy and cholecystojejunostomy in reconstruction consisted of end-to-end choledochocholedo-
Over a 4-yr period that began October 1, 1986, 103 orthotopic liver transplants were performed on 91 patients at the Johns Hopkins Hospital. Biliary reconstruction at the time of transplantationwas performed in standard fashion by an appropriately trained member of the surgical team. Six (7%) patients developed biliary complications, which included three cases of common bile duct stricture and one case each of bile duct obstruction caused by biopsy-related hemobilia, biloma and a retained fragment of a T tube after removal. Five of the six patients were treated successfully by nonoperative interventional radiological procedures performed under local anesthesia with light intravenous sedation. Reoperative surgery (to remove the T-tube fragment from subcutaneous tissue)was requiredfor only one patient, and no deaths (0 of 91) were attributable to biliary complications. All six patients are alive and well 6 to 33 mo after the operation with excellent liver function. Our findings would suggest that most biliary complications of orthotopic liver transplants are avoidable and that the few that do appear can usually be managed both safely and effectively by an interventional radiological ap1991;1 4 s18-823.) proach. (HEPATOLOGY
Received February 4, 1991; accepted June 19, 1991. Address reprint requests to: Dr. Andrew S. Klein, Department of Surgery, The Johns Hopkins Hospital,600 North Wolfe St., Baltimore, MD 21205. 31/1/32289
chostomy in 94 cases and Roux-en-Y choledochojejunostomy in 9 cases. The latter method was used for small children and for adults with sclerosing cholangitis or inadequate or diseased recipient common bile ducts. Biliary tract integrity was routinely assessed by intraoperative cholangiogram at the completion of the biliary anastomosis and 7 to 10 days after
Vol. 14, No. 5, 1991
REDUCED BILIARY COMPLICATIONS AFTER LIVER TRANSPLANT
FIG.2. Stricture was dilated with 7 mm angioplasty balloon and stented with 16 French Silastic drainage tube. Note postdilatation extravasation (short arrow) at angioplasty site.
FIG.1. Cholangiogram performed through T-tube tract 2 mo after liver transplant demonstrates high-grade stenosis (arrow)of common bile duct anastomosis.
the operation by T-tube cholangogram before internalization of the T tube. Patients were readmitted 4 mo after the operation for T-tube removal preceded by routine cholangiography. Those patients with no external access to their biliary tree (Row-en-Y choledochojejunostomies) underwent scintigraphic evaluation of their livers. No complications were seen among those patients who had reconstruction by way of choledochojejunostomy. The six patients reported in this series who had biliary complications develop were adults who had end-to-end choledochocholedochostomies performed with interrupted 5-0 Prolene sutures. The anastomoses were stented with No. 8 to No. 12 latex T tubes exited through the recipient common bile duct. Intraoperative and predischarge cholangiograms were interpreted as normal in all six patients who left the hospital with normal liver function. Median length of patient follow-up in this series was 25 mo.
RESULTS Of the three patients who had biliary strictures develop, one was asymptomatic with mild elevation of his serum transaminases. His stricture was discovered on routine T-tube cholangiography 5 mo after the
FIG.3. One month after stenting with 18F soft Silastic catheter. Catheter was withdrawn below stricture, and a cholangiogram was performed. Residual stenosis is appreciated, but intrahepatic biliary duct is rapidly drained through stenotic segment.
KLEIN ET AL.
FIGS.4 and 5.Anterior/posterior (Fig. 4) and left anterior oblique (Fig. 5) views from T-tube cholangiogram demonstrate significant extravasation (arrows) from the region of the bile duct anastomosis.
operation. Partial biliary obstruction was suspected in the remaining two patients who had marked elevations of their serum bilirubin and/or alkaline phosphatase develop 2 and 7 mo, respectively, after their liver transplants. All three patients were treated with balloon cholangioplasty and percutaneous stenting. The T-tube cholangiogram from the patient suspected of having biliary disease 2 mo after the operation demonstrated a tight stricture at the biliary anastomosis (Fig. 1). A 7 mm angioplasty balloon was used to dilate the stenotic segment that was then stented from below with a 16F soft Silastic tube (Fig. 2), subsequently upsized to an 18F Heyer-Schulte tube. Although residual stenosis was noted 7 mo after dilatation (Fig. 3), the intrahepatic biliary tree rapidly drained distal to the stricture. The patient remains clinically well with normal liver function tests 14 mo after stent removal. The two other patients with biliary strictures treated by balloon dilatation and stenting are also well with normal liver function 15and 16 mo, respectively, after stent removal. However, one of these patients has recently undergone successful endoscopic retrograde cholangiography and balloon dilatation of an asymptomatic recurrent bile duct stricture. The patient with the biloma presented to the transplant clinic within 3 mo of his transplant with fever, unexplained leukocytosis (WBC 30,000), alkaline phosphatase of 225 I U L and serum bilirubin of 2.7 mg/dl. A T-tube cholangiogram taken at that time demonstrated a leak from the region of the choledochocholedochostomy (Figs. 4 and 5 ) . The patient was allowed to
drain externally from his T tube for 8 days, after which time a repeat cholangiography showed no evidence of extravasation (Fig. 6). The T tube was removed 4 mo later, and the patient, who has returned to active duty with the local police force, has had no further difficulties over the last 15 mo. The remaining two patients in this study developed unusual biliary complications not related directly to intraoperative manipulation or reconstruction of their bile ducts. One man had hemobilia develop after percutaneous liver biopsy and required transfusion of 4 units of packed red cells for 48 hr. A source of bleeding could not be detected angiographically. An injectable guidewire was passed through the T-tube tract and positioned in the proximal right hepatic duct. Contrast injection demonstrated filling defects throughout the intrahepatic and extrahepatic biliary tree consistent with clot (Fig. 7). Percutaneous biliary drainage was established with an 8F multiple sidehole straight drain positioned above the anastomosis, and an 8F all-purpose drain was passed through the T-tube tract into the distal common bile duct to maintain patency of the tract (Fig. 8).The 8F multiple sidehole catheter was subsequently exchanged for a 10F straight drain positioned across both right and left ducts for increased external drainage (Fig. 9). Two months later all drains were removed, and no evidence of recurrence was seen at 3 mo follow-up. The remaining patient had a complication develop that was directly related to the mechanical failure of the T tube itself, which was retained internally after attempted removal. Endoscopic retrograde cholangiopan-
Vol. 14,No. 5, 1991
REDUCED BILIARY COMPLlCATIONS AFTER LlVER TRANSPLANT
FIG. 6. Follow-up T-tube cholangiogram obtained 8 days later demonstrates patent common bile duct anastomosis (arrow) and nondilated intrahepatic biliary tree. There is no evidence of cont.rast extravasation from the anastomosis.
FIG.7. Injectable guidewire (arrow)has been manipulated through the T-tube tract and positioned in proximal right hepatic duct. Contrast injection demonstrates filling defects throughout intrahepatic and extrahepatic biliary tree consistent with clot.
creatography failed to identify the tube within the bile duct, and the retained fragment appeared to be lodged intraabdominally. It was removed while the patient was under a general anesthetic, and the patient recovered without sequelae. DISCUSSION
Although biliary reconstruction is often considered the least technically demanding of the liver transplant anastomoses, it nonetheless remains a significant source of postoperative morbidity and mortality in many series. Strictures and leaks account for most of these complications, which are usually recognized within several weeks or months of the transplant procedure (4, 12). Such early presentation is similar to that previously documented for benign nontransplant postoperative biliary strictures, 70%of which are apparent by 6 mo and more than 80% of which are diagnosed by 1 yr (13). Although late biliary complications after bile duct injury are a recognized occurrence, a recent review by Stratta et al. (9) of 264 consecutive orthotopic liver transplants indicated a mean time for diagnosis of this occurrence of 49 days (range = 2 to 300 days). Ischemic injury to the extrahepatic biliary tree, which in the nontransplant patient is frequently attributed to the injudicious placement of ligatures, sutures or ligaclips, is also implicated as a causative factor in liver transplant biliary problems. Perfusion of the donor common bile duct is totally dependent on hepatic artery
FIG. 8. After opacification of biliary tree percutaneous biliary drainage has been performed with an 8F multiple sidehole straight drain (long arrow). Drain has been positioned above surgid anastomosis. Note clearing of clots from biliary tree that followed gentle flushing through straight drain. The 8F all-purpose drain (short arrow) has been passed through T-tube tract to level of common bile duct to maintain patency of tract.
KLEIN ET AL.
FIG.9. Ten days after percutaneous biliary drainage, 8F multiple sidehole catheter was exchanged for 10F straight drain (arrow) positioned across both right and left ducts to provide increased external drainage. No evidence of blood clots within the intrahepatic or extrahepatic biliary tree was noted at this time.
blood flow, and thus this structure is most susceptible to ischemic damage and the secondary development of strictures or leaks. A number of technical maneuvers have been suggested to decreasethe biliary complication rate related to liver transplants. Devascularization of the extrahepatic bile ducts can result from excessive dissection or stripping of the periductal tissues at the time of organ procurement. Extensive “cleaning” of either donor or recipient bile duct should be avoided, and, during the reimplantation phase, active bleeding from the cut ends of both structures should be confirmed before a choledochocholedochostomy is performed. When a choledochojejunostomy is necessary, one should not be concerned that the blood supply to the defunctionalized limb of the Roux-en-Y loop has been compromised. In either instance, control of excessive bleeding from the bile duct with fine monofilament sutures is preferable to the electrocautery, which may cause significantly more tissue necrosis than is immediately apparent. In the nontransplant patient, operative repair of bile duct strictures can be difficult. One review of 38 series reported a combined operative mortality of 8.3% (14). Reoperative biliary surgery after liver transplantation can be an even more formidable undertaking. Recent advances in the field of interventional radiology have provided nonoperative alternatives for many of these patients. Most procedures can be performed under local anesthesia with intravenous sedation, and thus the
patients can avoid the risks associated with a general anesthetic. Percutaneous transhepatic access to the biliary tree allows for rapid decompression of the obstructed bile duct(s) through external drainage. Balloon cholangioplasty can then be performed to dilate the stricture. Stents are left in place to maintain a luminal diameter during the healing process and also provide ready access for follow-up cholangiography, dilatation or both. The optimal length of time stents should be left in place is controversial. Pitt et al. (13) found that prolonged biliary stenting after operative repair of the bile duct decreased the incidence of recurrent stenosis. The three patients in this series who underwent balloon dilatation of their strictures were all stented for at least 6 mo. Stents were changed at 2-mo to 3-mo intervals to prevent biliary sludge accumulation, and when indicated the stents were upsized to a larger diameter catheter. No complications were seen associated with the interventional radiological procedures performed on the group of patients reported in this series. However, the risks of bleeding, hemobilia, cholangitis, pancreatitis and biliary fistula after percutaneous transhepatic cholangiography and balloon dilatation are well recognized (15). The fact that four of the five patients who were treated by the methods described above have not experienced recurrent biliary problems is encouraging, despite the relatively short follow-up interval of 16, 15, 14 and 5 mo, respectively. Other centers have reported favorable experience with the endoscopic approach to cholangiography and treatment of posttransplant biliary complications (10). It has been argued that such techniques avoid hepatic parenchymal trauma, are less painful and are tolerated better by the patient. We would agree that the endoscopic route may be preferable for selected cases, and, indeed, the single recurrent bile duct stenosis in this series was successfully managed by endoscopic retrograde cholangiography and dilatation. It must be recognized that such techniques carry their own set of associated risks, including pancreatitis, bile duct and duodenal perforation, endoprosthesis migration, the need for repeat endoscopy whenever follow-up imaging is necessary and lower probability of technical success (16, 17). This last problem was emphasized in several recent articles, including a review by Dondelinger and Kurdziel (161, which reported technical failure rates of 9%to 60%.In the final analysis, however, the decision between using either a percutaneous or an endoscopic approach to biliary complications may rest with the expertise available at a given transplant center. We would suggest that most biliary complications of liver transplantation are avoidable. The few that do appear can usually be managed by interventional radiological procedures, which offer an effective, low-risk alternative to reoperative surgery. REFERENCES 1. Eid A, Steffen R, Sterioff S, Porayko MK, Gross Jl3 Jr, Wiesner RH, Krom RAF. Long-term outcome after liver transplantation. Transplant Proc 1989;21:2409-2410.
Vol. 14, No. 5, 1991
REDUCED BILIARY COMPLICATIONS AFTER LIVER TRANSPLANT
2. Starzl TE, Putnam CW, Hansbrough JF, Porter KA, Reid HAS. Biliary complications after liver transplant with special reference to the biliary cast syndrome and techniques of secondary duct repair. Surgery 1977;81:212-221. 3. Wolff H, Otto G, David H. Biliary tract reconstruction in liver transplantation. Transplant Proc 1985;17:274-275. 4. Lerut J , Gordon RD, Iwatsuki S, Esquivel CO, Todo S, Tzakis A, Starzl TE. Biliary tract complications in human orthotopic liver transplantation. Transplantation 1987;43:47-51. 5. Wilson BJ, Marsh JW, Makowka L, Stieber AC, Koneru B, Todo S, Tzakis A, et al. Biliary tract complications in orthotopic adult liver transplantation. Am J Surg 1989;158:68-70. 6. Zajko AB, Campbell WL,Bron KM, Lecky JW, Iwatsuki S, Shaw BW J r , Starzl TE. Cholangiography and interventional biliary radiology in adult liver transplantation. AJR Am J Roentgenol 1985;144:127-133. 7. Zemel G, Zajko AB, Skolnick ML, Bron KM, Campbell WL. The role of sonography and transhepatic cholangiography in the diagnosis of biliary complications after liver transplantation. AJR Am J Roentgenol 1988;151:943-946. 8. Zajko AB, Bron KM, Campbell WL, Behal R, Van Thiel DH, Starzl TE. Percutaneous transhepatic cholangiography and biliary drainage &r liver transplantation: a five year experience. Gastrointest Radio1 1987;12:137-143. 9. Stratta RJ, Wood R, Langnas AN, Hollins RR, Bruder KJ, Donovan JP, Burnett DA, et al. Diagnosis and treatment of biliary tract complications of the orthotopic liver transplantation. Surgery 1989;106:675-683.
10. Ostroff JW, Roberts JP, Gordon RL, Ring EJ, Ascher NL. The management of t-tube leaks in orthotopic liver transplant recipients with endoscopically placed nasobiliary catheters. Transplantation 1990;49:922-924. 11. Gordon RD, Iwatsuki S, Esquivel CO, Makowka L, Tzakis AG, Todo S, Starzl TE. Liver transplantation. In: Cerilli GJ, ed.Organ transplantation and replacement. Philadelphia: JB Lippincott Co., 1988~521-526. 12. Wall WJ, Grant DR, Mimeault RE, Girvan DP, Duff JH. Biliary tract reconstruction in liver transplantation. Can J Surg 1989; 32:97-100. 13. Pitt HA, Miyamoto T, Parapatis SK, Tompkins RK, Longmire WPJ. Factors influencing outcome in patients with postoperative biliary strictures. Am J Surg 1982;144:14-21. 14. Warren KW, Christophi C, Armendin ZR. The evolution and current prospectives of the treatment of benign bile duct strictures: a review. Surg Gastroenterol 1982;1:141-154. 15. Pitt HA, Kaufman SL, Coleman J , White RI, Cameron JL. Benign postoperative biliary strictures: operate or dilate? Ann Surg 1989;210:417-427. 16. Dondelinger RF and Kurdziel CJ. Biliary endoprostheses in malignant obstruction. In: Dondelinger RF, Rossi P, Kurdziel JC, Wallace S, eds. Interventional radiology. New York Thieme Medical Publishers, Inc., 1990:200-208. 17. Lammer J, Neumayer K. Biliary drainage endoprostheses: experience with 201 placements. Radiology 1986;159:625-629.