Chappet1 in 1894 was the first to report and Caroli et al.2 in 1959 was the first to give the anatomic description of biliary papillomatosis. Since then, approximately 60 cases have been reported in the literature worldwide; to our knowledge, only 6 cases have been reported to be treated with liver transplantation.3–8 This rare disease is seen more often in the middle-aged and elderly adults; the male/female ratio is 2:1. The disease is considered idiopathic even in cases that coexist with chronic biliary lithiasis, Caroli disease, clonorchis infestation, polyposis coli, and hepatitis B or C.9 It is characterized by relapsing episodes of obstructive jaundice and cholangitis. The latter could lead to secondary cirrhosis and death from sepsis or liver failure, and it is regarded as premalignant lesion because of the high rate of malignant transformation (25-50%).6, 8, 10 It is accompanied by poor 5-year survival (40%).6, 11
Approximately 60 cases of biliary papillomatosis have been reported in the world literature, while only 6 cases have been reported to be treated with liver transplantation. This rare disease, which is characterized by relapsing episodes of obstructive jaundice and cholangitis that lead to secondary cirrhosis and death from sepsis or liver failure, it is also considered premalignant because of its frequent malignant transformation (25–50%). We present a case of a 43-year-old white man with papillomatosis of intra- and extrahepatic biliary tree who sought care for repeated episodes of obstructive jaundice and cholangitis. The diagnosis was suspected after endoscopic retrograde cholangiopancreatography and confirmed by liver and common bile duct biopsies. The patient underwent orthotopic liver transplantation with Roux-en-Y hepatico-jejunostomy to treat end-stage liver cirrhosis. Fifteen months' follow-up revealed a patient with normal graft function and with no clinically or laboratory findings of disease recurrence or cancer development. Liver Transpl 13:1045–1048, 2007. © 2007 AASLD.
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A 43-year-old white man sought care at our department for papillomatosis of the intra- and extrahepatic biliary tree. During the last 4 years, the patient had experienced repeated episodes of obstructive jaundice and recurrent cholangitis.
The patient's medical history included 3 related surgeries. In 2001, the patient sought care for obstructive jaundice, with serum bilirubin peaking at 24 mg/dL, and underwent cholecystectomy elsewhere. In 2002, a stent was inserted in the common bile duct during endoscopic retrograde cholangiopancreatography, and in 2004, an exploratory laparotomy was performed for repeated episodes of cholangitis. During the last operation, a choledochotomy and cholangioscopy were performed, which revealed extensive masses and stones in the left and right intra- and extrahepatic bile ducts, into which they had abstracted; nevertheless, all the intrahepatic papillomas were not removed. At the same time, a postoperative omphalocele and celiocele at the right side of the abdominal wall were restored. At the time of the last operation, total serum bilirubin was 12.8 mg/dL, direct serum bilirubin was 9.8 mg/dL, and alkaline phosphatase and gamma glutamyl transferase were 2- and 6-fold beyond normal values, respectively. Aspartate aminotransferase, alanine aminotransferase, carcinoembryonic antigen, and alfa-fetoprotein were within normal values; CA 19-9 was increased 6-fold.
Family medical history was free of papillomatosis, polypoidosis, and gastrointestinal tumors. Pretransplantation evaluation revealed a patient with Child-Pugh class A liver cirrhosis. Preoperative workup failed to reveal any marked alterations in aspartate aminotransferase, alanine aminotransferase, and gamma glutamyl transferase except a 2-fold increase in alkaline phosphatase levels. A new endoscopic retrograde cholangiopancreatography (Fig. 1) revealed velvety papillary growths with small, oval, soft, white to red masses filling the dilated ducts. Common bile duct biopsy revealed papillomatosis with mild dysplasia of the epithelium.
The patient underwent a piggyback orthotopic liver transplantation in July 2005 with Roux-en-Y hepatico-jejunostomy (Fig. 2).
Liver sections from the right and left lobe showed severe papillomatosis with moderate epithelial dysplasia in many bile ducts (this feature is not demonstrated in the images because of the low power of the photomicrographs), mainly located in the hilar region (Figs. 3 and 4).
Roux-en-Y hepatico-jejunostomy was preferred to duct-to-duct anastomosis because of the increased risk of recurrence. At the time of transplantation, the disease did not extend to the pancreatic duct, and pancreatoduodenectomy was avoided. The patient had an uneventful postoperative course and was discharged at on postoperative day 30. At 15 months' follow-up, the patient had normal graft function and showed no signs of recurrence or cancer. Follow-up consists of physical examination, laboratory studies, and imaging with regular computed tomography of the liver, and magnetic resonance imaging cholangiopancreatography every 6 months during the first 2 years and once a year after that.
Biliary papillomatosis is regarded as a rare entity, and it remains a disease of unknown cause and pathogenesis, with no established relationship with other diseases of the biliary tract.12 Zen et al.,13 using a considerable number of biliary papillary tumors and intraductal papillary mucinous neoplasm, showed sufficient evidence that biliary papillomatosis and papillary-cholangiocarcinoma with or without mucus hypersecretion potentially belong to a single tumor entity of intraductal papillary neoplasm of the bile duct. Biliary papillomatosis is considered an extremely rare disorder and is characterized by the presence of numerous mucin-secreting papillary adenomas within the extrahepatic and/or intrahepatic biliary tree. Lee et al.14 proposed that biliary papillomatosis should not be regarded as a benign disease with low malignant potential, but rather as a premalignant lesion with high malignant potential, and that the pathogenesis of progression from benign to malignant disease may follow the adenoma-carcinoma sequence. It typically presents with relapsing bouts of obstructive jaundice and cholangitis thought to be caused by intermittent biliary obstruction from secreted mucus or sloughed tumour fragments. Topographic distribution of the papillary tumors at the time of diagnosis in the biliary tree consists in extra- and intrahepatic localization in 58%, exclusively intrahepatic in 22%, exclusively extrahepatic in 14%, only in 3%, and extrahepatic biliary tract and pancreatic duct in 3%.11,15.16 Clinically, papillomatosis manifests as obstructive jaundice attacks and/or relapsing cholangitis. The obstruction of the biliary tree is attributed to either the adenomas themselves or to the produced debris of cells and mucus. Mucus can be detected by duodenoscopy and endoscopic retrograde cholangiopancreatography, which is strongly indicative of biliary papillomatosis.
Resection is still considered to be the treatment of choice when macroscopic disease is localized and the patient is able to withstand major surgery. On the other hand, surgical treatment can be considered controversial because of the associated high incidence of recurrence of local disease and frequent transformation to malignancy, which increases the need for reoperation.10, 11, 17 Survivals of more than 12 months are exceedingly rare. Dumortier et al.5 were the first to report a patient with biliary papillomatosis treated with orthotopic liver transplantation, which has been proposed as the only way to avoid recurrence and degeneration. The above-mentioned group proceeded with a Whipple pancreatoduodenectomy to rule out any possibility of recurrence.
In our case, papillomatosis was predominantly localized in the intrahepatic biliary tree bilaterally, and it was decided to manage the patient with orthotopic liver transplantation. At the time of surgery, a Whipple pancreatoduodenectomy was avoided because of lack of evidence of pancreatic duct involvement. Even though our patient has had, as of this writing, 15 months of follow-up without recurrence, long-term follow-up is still warranted for these patients to see whether liver transplantation could be the treatment of choice for biliary papillomatosis.