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CASE REPORT
Successful Orthotopic Liver Transplant for Diffuse Biliary Papillomatosis With Malignant Transformation: A Case Report With Long-Term Follow-Up

In patients with biliary papillomatosis, complete resection of the biliary tree (that is, liver transplant along with duodenocephalo-pancreatectomy) is considered the only potential curative treatment, given its diffuse pattern and likelihood of malignant transformation. Nevertheless, such a combined surgical approach can increase patient morbidity and mortality and should be considered only when the distal part of the common bile duct is involved. Here, we avoided duodenocephalo-pancreatectomy in a patient with distal common bile duct free from disease; this approach did not negatively influence survival and appeared to be safer during liver transplant.


Key words : Cholangiocarcinoma, Duodenocephalo-pancreatectomy, Liver transplantation

Introduction

Biliary papillomatosis is a rare disease of the biliary tract that was first reported in 1984 by Chappet and associates1 and later anatomically described in 1959 by Caroli and associates.2 To date, about 200 cases have been so far described.3 This disease, charac­terized by the presence of multiple papillary tumors of both intrahepatic and extrahepatic bile ducts, is more frequent in the sixth decade of life, and the male-to-female ratio is approximately 2:1.4 The cause remains unclear.

The typical clinical features of biliary papillo­matosis are abdominal pain, jaundice, and relapsing episodes of cholangitis, due to biliary tract occlusion by biliary stones, mucous plugs, tumor detritus, and blood clots.5 Hemobilia is rare in the setting of biliary papillomatosis.6,7 Recurrent superinfections of the biliary tract can lead to secondary biliary cirrhosis, with subsequent liver failure.8-11

Two striking features of the disease are the widespread pattern along the biliary tract, which is responsible for high rates of recurrence after resection, and the likelihood of malignant transformation.4 Accordingly, complete resection of the biliary tree, obtained with liver transplant accompanied by duodeno-cephalopancreatectomy (DCP), is the only potential curative treatment.12

We report the case of a young man with biliary papillomatosis without evidence of involvement of the distal part of the biliary tract who underwent liver transplant without DCP. Written informed consent was obtained from the patient for publication of this case report and any accompanying images.

Case Report

A 38-year-old man was admitted to the emergency unit of our hospital for obstructive jaundice without signs of cholangitis. Laboratory tests showed mild elevation of alanine aminotransferase and aspartate aminotransferase levels but highly elevated levels of bilirubin (26.5 mg/dL), gamma glutamyltransferase (670 mUI/mL), and alkaline phosphatase (1012 U/L). The patients also showed mild signs of hepatocellular necrosis. Serum alpha-fetoprotein, carcinoembryonic antigen, and carbohydrate antigen 19-9 levels were within the normal range. A chromogranin A serum level of 164 ng/mL (range from 19.4 to 98.14 ng/mL) was recorded. Tests for hepatitis B and C virus were negative.

Preoperatively, the patient underwent radiologic examinations (ultrasonography, computed tomog­raphy, and magnetic resonance imaging), which showed evidence of bilateral intrahepatic biliary tract dilatation due to the presence of a neoplasm located at the biliary convergence. However, there was no evidence of invasion of the liver pedicle or involve­ment of the common bile duct. An endoscopic retrograde cholangiopancreatography displayed a normal common bile duct with stenosis at the bile duct convergence and intrahepatic bile duct dilatation.

A diagnostic laparotomy with intrahepatic and extrahepatic biliary duct exploration by cho­langioscopy, cholecystectomy, T-tube drainage, and liver biopsy was performed. Biopsy results showed the histologic presence of an in situ papillary adenocarcinoma associated with biliary papillomatosis and secondary biliary cirrhosis. The gallbladder was free from disease.

Because of evidence of relapsing episodes of cholangitis but radiologic findings showing disease stability, we placed the patient on a liver transplant wait list. The patient then underwent liver transplant with choledochojejunostomy and Braun entero­enterostomy. The donor was both hepatitis C and hepatitis B positive (informed consent was obtained from the patient). Frozen sections of the common bile duct margin of resection were free from disease. Histologic examination of the specimen revealed the presence of a solid, grayish, 5-cm neoplasm in the hilar region and multiple neoplastic nodules in the remaining liver parenchyma (Figure 1). A diagnosis of well-differentiated multicentric adenocarcinoma of the intrahepatic biliary ducts was made. No lymphatic metastases were found. Induction immuno­suppression consisted of prednisone, tacrolimus, and mycophenolate mofetil. The posto­perative course was uneventful, and the patient was discharged on postoperative day 18.

During follow-up, at 3 years after liver transplant, a computed tomography scan showed an enlargement of the pancreatic head due to a formation, with fluid density and irregular contrast enhancement. An endoscopic ultrasonography was performed, and a hypoechoic cystic mass of the pancreatic head with a papillary hyperechoic intraluminal formation was revealed. Fine needle aspiration was performed, with results showing a cytologic pattern of papillomatosis without atypia. Given that a diagnosis of recurrent fibrosis F3/F4 of the graft was made, we decided not to perform DCP.

During follow-up, the lesion of the pancreatic head had slightly grown, but there was no evidence of recurrent disease (Figure 2). At the moment, the patient is asymptomatic.

Discussion

Biliary papillomatosis is a rare pathology of the biliary tract characterized by the presence of multiple papillary tumors in the biliary tree. To date, its cause and pathogenesis remain unclear, although an association between chronic inflammation due to stones, infections, and pancreatic juice and mucosal metaplasia and/or dysplasia has been previously suggested.13 According to the World Health Organization, given the similar behavior of biliary papillomatosis with its pancreatic counterpart, this entity has been renamed biliary intraepithelial papillary neoplasia.14 In 2004, Lee and associates reviewed 58 cases of biliary papillomatosis and reported an 83% rate of presence of malignant transformation in adenocarcinoma or mucous carcinoma in the setting of biliary adenomas, suggesting that, rather than previously believed on the basis of few anecdotal series, biliary papillomatosis should be considered as a premalignant condition with high malignant potential, in the setting of a continuous histologic spectrum ranging from dysplasia to carcinoma with biliary features.15 On the other hand, in 2003, Yeung and associates highlighted a transformation rate of 42% in 78 patients, and only 55% of patients could undergo curative resection at the moment of diagnosis.4

It is noteworthy that the spreading pattern of the disease along the biliary tract accounts for the high recurrence rate after resection.8,9,15 Those elements have led investigators to conclude that the only potentially curative treatment is the resection of the whole biliary tree, achieved with liver transplant plus DCP, when feasible. Nevertheless, in our patient, there were no signs of involvement of the distal part of the common bile duct at time of liver transplant; therefore, we decided not to perform DCP. Biliary reconstruction was made with a choledochojejunostomy and Braun enteroenterostomy to prevent the development of biliary obstruction in case of relapse of the disease in the distal stump of the common bile duct. Although recurrence developed 3 years after liver transplant, the patient has remained asymptomatic so far during follow-up, which has lasted for about 120 months.

In conclusion, DCP along with liver transplant for the treatment of biliary papillomatosis is mandatory when the distal part of the common bile duct is involved. However, DCP can be avoided, although with a risk of recurrence that will not cause cholestasis as long as the choice for biliary reconstruction is a choledochojejunostomy. Provided that there is strict patient follow-up, this approach does not seem to negatively influence survival, even when malignant transformation is present on histologic examination, and may be safer at the time of transplant.


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DOI : 10.6002/ect.2017.0134


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From the General Surgery and Organ Transplantation Unit, San Camillo Hospital, Rome, Italy
Acknowledgements: The authors have no sources of funding for this study and have no conflicts of interest to declare.
Corresponding author: Daniele Ferraro, General Surgery and Organ Transplantation Unit, San Camillo Hospital, Cir. ne Gianicolense, 87, 00152 Rome, Italy
Phone: +39 3497364780
E-mail: daniele.ferraro.md@gmail.com