Biliary Tract Complications in Transplantation Under Cyclosporin-Steroid Therapy

S. Iwatsuki, B. W. Shaw, Jr., and T. E. Starzl

OMPLICATIONS of recon­ tube (usually infant ) was used as a stent. one C struction in are end passing through the papilla of Vater into the duode­ num (choledocho-choledochostomy with straight tube more frequent than those of vascular anasto­ stent. C-C-S), moses.I. 2 In earlier times, unrecognized bile End-to-side choledocho- in Roux-en-Y duct obstruction was frequently mistaken for with a straight tube stent (C-J-S) became the first choice graft rejection, and unwise decisions to when the recipient's bile duct was absent (in biliary increase immunosuppression often resulted in atresia) or diseased (in sclerosing cholangitis. bile duct cancer. or secondary biliary cirrhosis). When the donor's fatal septic complications. In other cases, bil­ common bile duct was used for bile duct reconstruction. iary leakage and peritonitis in the early post­ the was always removed, operative period limited the adequate use of Cholecysto-jejunostomy in Roux-en-Y (Cy-J). tube immunosuppression, resulting in acute graft . or tube choledochostomy were used only rejection superimposed on serious septic bil­ when the operation was so difficult and the patient was so unstable that better bile duct reconstruction could not be iary peritonitis. performed. The problems caused by biliary complica­ tions under conventional immunosuppression Case Materials have been reported in our series I and in the During the 29 months between March 1980 and July Cambridge series.2 These, directly or indirect­ 1982.78 patients received 90 orthotopic liver transplanta­ ly, caused death in many cases. In this article tions under cyclosporin-steroid therapy. Of the 78 the incidence, nature and management of patients 30 were 5.5 months to 18 years old and 48 were adults (19-57 years). Three pediatric and 5 adult patients biliary complications after liver transplanta­ underwent liver transplantation twice. and two more tion will be reported in patients under cyclo­ pediatric patients were transplanted three times. sporin-steroid therapy. The indications for operation in 30 pediatric patients were: biliary atresia or hypoplasia (I3 cases). alpha­ MATERIALS AND METHODS I-antitrypsin deficiency disease (4), chronic aggressive hepatitis (3), Byler's disease (3), and I case each of Methods of Bile Duct Reconstruction secondary biliary cirrhosis. Budd-Chiari syndrome. neo­ End-to-end choledocho-choledochostomy was the first natal hepatitis, Wilson's disease. tyrosinemia, type I choice of bile duct reconstruction whenever donor's and glycogen storage disease. and Sea-Blue Histiocyte syn­ recipient's common bile ducts were adequate in size and drome. Those for the 48 adult patients were chronic active quality. AT-tube was used as a stent through a small hepatitis (15 cases), malignancy (9). primary biliary choledochotomy on the recipient's common bile duct cirrhosis (8). sclerosing cholangitis (6), secondary biliary when both the donor's and recipient's common bile ducts cirrhosis (4). alpha-I-antitrypsin deficiency disease (2), were large enough to accept at least a French no. 8 T-tube Budd-Chiari syndrome (2). adenomatosis (1). and alco­ (choledocho-choledochostomy with T-tube stent, C-C-T). holic cirrhosis (I). Thus. 14 of 30 pediatric patients and When the bile ducts were too small to accept a T-tube. or 12 of 48 adult patients had absence of a primary disease when choledochotomy was considered unwise. a straight of the extrahepatic biliary system.

RESULTS From the Department of , University Health Choledocho-choledochostomy With T- Tube Center of Pillsburgh, Pillsburgh, Pa. Supported in part by NIH Grants AM 29961-02 and Stent AM 30183"()1. Choledocho-choledochostomy with T -tube Reprint requests should be addressed /0 Dr. S.lwatsu­ stent (C-C-T) was used in 29 liver transplants ki, University Health Center of Pittsburgh, 1084 Scaife (6 pediatric and 23 adult transplants). No Hall, Pittsburgh, Po. 15261. © 1983 by Grune & Stratton, Inc. complications related to bile duct reconstruc­ 0041-1345/83//501-0310101.00/0 tion have developed in 24 (83%) of 29 trans-

1288 Transplantation Proceedings, Vol. XV, No.1 (March), 1983 BILIARY TRACT IN LIVER TRANSPLANTS 1289 plants during the follow-up period. However, tion for postoperative hemorrhage within 24 in 5 (17%), complications have developed. In . hr after transplant. A straight tube stent was two (OT 218, 237), a small leakage of dye replaced by a T-tube inserted through the from a T-tube insertion site was discovered by donor common bile duct, and the duct anasto­ routine posttransplant mosis was repaired. This patient died on the within 2 weeks. Despite the absence of clinical third day from graft failure due to poor pres­ manifestation of bile leakage, the area was ervation. In two cases (OT 194, 210) choledo­ promptly drained by penrose drains through cho-choledochostomy broke down 5 days and the previous right subcostal incision. The bile 3 weeks after transplant. Revision of choledo­ leakage ceased within a week. cho-choledochostomy with T-tube in case OT In case OT 235, routine cholangiography 194 and a choledocho-jejunostomy in Roux­ revealed a significant leakage through the en-Y in case OT 210 have been successful for anastomosis. A small breakdown of choledo­ more than a year in the former and for 8 cho-choledochostomy was repaired and the months in the latter. A large infarct and a area was drained by penrose drains. A few breakdown of choledocho-choledochostomy days later, the repaired anastomosis broke occurred simultaneously in a pediatric recip­ down and a large amount of bile drained ient (OT 184) 17 days after transplant. The through penrose drains. The leak was finally abdominal incision was left wide open for controlled by excision of previous anastomosis adequate drainage for 2 weeks and then the and a new choledocho-choledochostomy with biliary system was reconstructed with hepati­ aT-tube stent. In case OT 221, routine post­ cojejunostomy in Roux-en-Y. This child has transplant cholangiography did not reveal any been well for almost 2 years after transplant leakage at 2 weeks, but 6 weeks after trans­ with a large area of diffuse calcification in the plant the abdomen was explored for abdomi­ central portion of the liver. nal abscess. At that time, bile leak through a Biliary obstruction developed in two cases T-tube insertion site was found. Two months after C-C-S. In case OT 181, a straight tube after drainage of abdominal abscess and con­ stent could not be passed through the papilla trol of bile leak, this patient was discharged of Vater. The tube remained within the bile with a granulating abdominal wound, but duct and caused biliary obstruction. The tube without bile leak. In case OT 230, routine was removed 10 months after transplant by cholangiography revealed that the proximal choledochotomy. In case OT 193, the stent tip of T-tube was in the donor cystic duct tube was passed out of the bile duct within 10 instead of hepatic duct, causing a mild degree days after transplant. There was no immedi­ of biliary obstruction. The T -tube was replace ate biliary complication, but biliary stricture by a transhepatic biliary . Two at the anastomosis was documented by trans­ months later, the catheter was removed with­ hepatic cholangiography in the eighth post­ out any further biliary complications. transplant month. The obstruction was relieved by choledocho-jejunostomy in Roux­ Choledocho-choledochostomy With Straight en-Y 5 months ago. TubeStent A fistula between the hepatic artery and the Choledocho-choledochostomy with straight common bile duct developed in case OT 208 2 tube stent (C-C-S) was used in 22 transplants months after transplant with C-C-S. This rare (1 °pediatric and 12 adult transplants). Fif­ complication was manifested initially by sep­ teen (68%) of the 22 C-C-S have been suc­ ticemia, and following intermittent massive cessful without complications, but 7 (32%) upper gastrointestinal hemorrhage. Endo­ resulted in the following' complications. In scopic examination did not reveal any source case OT 187, bile leak through the anastomo­ of hemorrhage except large amounts of blood sis was incidentally found during reexplora- clots. Angiography revealed an aneurysm of ------~~~~-~

1290 IWATSUKI. SHAW. JR .• AND STARZI..

the hepatic artery, which suggested hemobilia cho-jejunostomy in the second posttransplant as a cause of hemorrhage. An exploratory month without further biliary complication at disclosed blood clots in the bile least for a year. The obstruction in another duct and a mycotic aneurysm of the hepatic case (OT 188) was caused by a ligature of artery close to the choledocho-choledochosto­ donor distal common duct involving the my. The hepatic artery was resected and was entrance of the cystic duct. The obstruction replaced with an arterial homograft. One was recognized on the seventh day and week later, the patient developed further mas­ relieved by choledocho-jejunostomy. How­ sive hemorrhage and expired in the third ever, this patient died from pulmonary sepsis posttransplant month. and liver failure on the 23rd day. A large liver abscess developed in a pediatric case (OT Choiedoch(rjejunostomy in Roux-en-Y With 191) 2 weeks after transplant. This complica­ Straight Tube Stent tion was successfully treated by a second liver transplant with choledocho-jejunostomy in Choledocho-jejunostomy in Roux-en- Y Roux-en-Y 3 weeks after the first transplant. with straight tube stent (C-J-S) was used in Pathologic examination of the first graft 24 transplants (17 pediatric and 7 adult trans­ revealed a large fungal abscess with a commu­ plants). This method has been successful in 22 nication to the right hepatic duct. This liver (92%) of 24 transplants during the follow-up abscess could have been a result of poor organ period. However, complications have devel­ preservation or of biliary duct obstruction. oped in two cases (8%). Bile leaked through This child has been well without biliary com­ partially broken choledocho-jejunostomy on plication more than a year after the second the third posttransplant day in case OT 100. liver transplant. One patient died from a Revision of choledocho-jejunostomy at the combination of unrecognized bile leak due to new site had been without further complica­ faulty ligature of the donor distal common tion until the death from recurrent bile duct duct. abdominal sepsis. and graft failure on carcinoma 9 months after transplant. In the 12th day. another case (OT 201), bile leak from the anastomosis was not recognized until I month Others after transplant when a small abscess at the Bile duct reconstruction was further com­ hepatic hilum was suggested by a CT scan and promised to tube cholecystostomy or choledo­ a transhepatic cholangiography. An attempt chostomy in 4 transplants (1 pediatric and 3 to drain the small abscess and to reconstruct adult transplants). One patient (OT 178) died the biliary system resulted in a massive hem­ on the second day before final bile duct recon­ orrhage from the portal vein, and the child struction. A second patient (OT 220) required died during the operation on the 33rd post­ another liver transplant for graft failure 5 transplant day. days after the first. A third patient (OT 294) underwent choledocho-jejunostomy in Roux­ Choiecyst(rjejunostomy in Roux-en-Y en-Yon the eighth day. This patient survived Bile duct reconstruction was compromised abdominal sepsis due to breakdown of the to cholecysto-jejunostomy (Cy-J) in 6 trans­ Roux-en-Y jejunojejunostomy and other com­ plants (3 pediatric and 3 adult transplants). plications and is well without further biliary Five (83%) of 6 cholecysto-jejunostomies complications in the tenth posttransplant resulted in 3 cystic duct obstructions and one month. A fourth patient is recovering from each of liver abscess and biliary abdominal abdominal sepsis with a tube cholecystostomy sepsis. In two cases (OT 176, 190) the in the second transplant month. obstructions were at the cystic duct. In both Five patients died intraoperatively before cases the obstruction was relieved by choledo- bile duct reconstruction was achieved. BILIARY TRACT IN LIVER TRANSPLANTS 1291

Table 1. Primary Bile Duct Procedure. and Complication.

ChoIedoch<>- Choledoch<>- Choledoch<>- jejunostomy ChoIecyst<>- choledochostomy choledochostomy in RooK-en-Y J41junostomy With T-Tube With Internal Stant With Stant in Roux-en-Y (C-C-TI (C-C-S) (C-J-S) (Cy-J)

Numbers 29 22 24 6 Success 24(83%) 15 (68%) 22 (92%) 1 (17%) Failwe 5 7 2 5 Nature of failure Obstruction 1 2 0 4· Bile leakage 4 4 2 1 Arterioductal fistula 0 0 0 Cause of death 0

·One patient developed a large fungal liver abscess, which led to retransplantation. He is doing well with the second liver graft 1 year later.

DISCUSSION as a 5.5-month-old baby. Despite this, there were only two biliary complications, one of Choledocho-choledochostomy is the ideal which was unfortunately fatal. This method of method of bile duct reconstruction, when fea­ bile duct reconstruction is time consuming sible, because it is the simplest and most and requires microsurgical technique, partic­ physiologic. Use of T-tube stent provides a ularly in pediatric transplants, but this is a protection of anastomosis from leakage and sound alternative to duct-to-duct anastomo­ stricture as well as easy access to bile duct sis. examination. Early recognition of subclinical Cholecysto-jejunostomy was used in the bile leak and obstruction leads to proper most adverse circumstances in the present prompt treatment and thus prevents the devel­ series, usually as a means of quickly terminat­ opment of serious complications. None of the ing the operation. Five complications ensued, 29 patients so treated in the present series died of which four were treated successfully. Three with biliary complications. A straight tube patients lived at least 1 year without further internal stent was used in less satisfactory biliary complications. Together with external conditions of bile duct reconstructions. Proba­ tube drainage, cholecysto-jejunostomy can be bly because of this, bile leak and obstruction used under adverse circumstances. occurred more frequently with straight tube When the donor common duct was used for stent than with T-tube stent. However, only either choledocho-choledochostomy or chole­ one pateint (OT 208) with straight tube stent docho-jejunostomy in Roux-en-Y, biliary died with biliary complication. complications occurred in 14 (19%) of 75 Choledocho-jejunostomy in Roux-en-Y transplants under cyclosporin-steroid thera­ with a straight tube stent was used when py. However, 12 of 14 complications were recipient common bile duct was not available treated successfully, and in only two patients for duct-to-duct anastomosis. This method were the biliary complications the direct or was applied on 17 pediatric recipients as small indirect cause of death (Table 1).

REFERENCES I. Starzl TE, Putnam CW, Hansbrough JF, et al: 2. Caine RY, Williams R: Curr Probl Surg 16:3, Surgery 81 :2 \2, 1911 1979