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Orthotopic Liver Transplantation for Biliary Atresia Complicated by Incidental Cholangiocarcinoma

Vera, Alonso*; Villaveces, Daniel; López, Rocio*

Journal of Pediatric Gastroenterology and Nutrition: September 2012 - Volume 55 - Issue 3 - p 336–337
doi: 10.1097/MPG.0b013e318233ff17
Case Reports

*University Hospital Fundación Santa Fe de Bogotá

Andes University Medical School, Bogotá, Colombia.

Address correspondence and reprint requests to Alonso Vera, MD, University Hospital Fundación Santa Fe de Bogota, Av. Cra. 9 # 116-20 Cons 307, Bogotá, Colombia (e-mail:

Received 23 March, 2011

Accepted 22 August, 2011

The authors report no conflicts of interest.

Biliary atresia (BA) is a rare disorder of neonates, which leads to biliary cirrhosis of the liver. Although the primary treatment is Kasai portoenterostomy, 46% of patients ultimately undergo liver transplantation. BA has been associated with the development of malignant hepatic tumors in the pediatric population (1,2). We found a case of BA complicated by cholangiocarcinoma in an 11-year-old girl who died 1 week after being diagnosed (2). Despite the fact that BA is the most common indication for liver transplantation in children, there are no reported cases of transplantation for BA associated with cholangiocarcinoma in the literature. We describe a patient who underwent liver transplantation for BA and was found to have an incidental cholangiocarcinoma on pathologic examination of the explanted liver.

A 16-year-old girl underwent orthotopic liver transplantation for cirrhosis secondary to BA in September 2007. She was diagnosed with BA when she was 20 days old and underwent a successful Kasai portoenterostomy at 109 days of age. The patient remained clinically stable until she was 15 years old, when she developed multiple episodes of variceal hemorrhage and progression of cholestasis.

She was then referred to our center and assessed for liver transplantation in August 2006. Full evaluation was satisfactory. The radiologic workup included computed tomography (CT) scan of the abdomen, Doppler ultrasound of the liver and portal system, and chest x-ray; none of which showed any finding suggestive of a tumor. One month before transplantation, an abdominal ultrasound showed no evidence of abdominal mass.

At admission for transplantation, liver function tests showed total bilirubin 11.24 mg/dL (nl 0–1), predominantly conjugated (8 mg/dL); alkaline phosphatase 835 IU/L (nl <750); aspartate aminotransferase 313 U/L (nl 5–34); alanine transaminase 139 U/L (nl <55); albumin 2.60 g/dL (nl 3.80–5.40); international normalized ratio 1.1; and a fibrinogen level of 275 mg/dL (nl 200–400). These findings were compatible with CHILD B (score for chronic liver disease), and Model for End-Stage Liver Disease chronic cholestatic liver disease.

An uneventful orthotopic liver transplantation with a piggyback technique was carried out in September 2007. She had a typical postoperative recovery and was discharged on day 15 with immunosuppressive therapy consisting of tacrolimus, mycophenolate, and prednisolone.

The pathology report of the explanted liver showed a complete loss of normal hepatic architecture and severe cholestasis compatible with secondary biliary cirrhosis, along with an intrahepatic (40 × 25 × 15 mm) (Fig. 1), moderately differentiated cholangiocarcinoma, with invasion into the surrounding hepatic parenchyma (2 × 3 mm), without vascular invasion and Ki-67 expression of 5% to 7%. Immunohistochemical markers showed focal positivity for CK 7, intense and diffuse positivity for CK 19, CA 19-9, CEA, and EMA, and negativity for CA-125 and CK 20. It was classified as a stage I tumor (T1, N0, M0). With liver transplantation, a total hepatectomy renders to an R0 resection (microscopical margins free of tumor), so the oncology team considered that the patient did not require any adjuvant therapy.



The patient developed right lower chest pain 6 months after transplantation. A chest CT scan showed a mass located on the right seventh rib, measuring 90 × 38 × 36 mm (Fig. 2). The patient underwent extensive resection of 2 ribs with polypropylene mesh and latissimus dorsi muscle flap reconstruction 20 months after transplantation, which resulted in an R0 resection of the metastasis. The pathologist confirmed histologic appearance of moderate and poorly differentiated cholangiocarcinoma with hepatocellular and ductal component, bone and vascular invasion, and Ki-67 expression of 50%. Four months later, a bone scintigraphy and full body CT showed multiple metastases to the rib cage, iliac bones, and left tibia. The patient began receiving palliative care with GEMOX protocol and radiotherapy for pain relief.



The patient is alive 33 months after transplantation, with extensive bone metastases. She was switched to an immunosuppressant regimen based on sirolimus, mycophenolate mofetil, and prednisolone, given sirolimus's antiproliferative properties, and remains with normal liver function tests.

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BA is an uncommon destructive inflammatory obliterative cholangiopathy of neonates that affects both intrahepatic and extrahepatic bile ducts. The pathophysiology of BA is largely unknown, but several factors have been implicated including genetic, inflammatory, infective, and toxic insults. If left untreated, BA will invariably lead to hepatic cirrhosis and death by age 2. BA is treated primarily with Kasai portoenterostomy, but 46% of patients ultimately undergo liver transplantation, thus becoming the most common indication for liver transplantation in the pediatric population.

Associations of BA with malignant hepatic tumors have been published in the literature. We found 2 published cases of BA complicated by cholangiocarcinoma (1,2). Neither of these 2 patients was subjected to orthotopic liver transplantation (OLT) as part of their treatment. We report herein the first case of a patient with BA and cholangiocarcinoma who underwent OLT.

The incidental finding of cholangiocarcinoma at the time of OLT has been studied elsewhere, mainly in cases when OLT was carried out for primary sclerosing cholangitis. In a study done on adult patients who underwent OLT with incidental cholangiocarcinoma found on the hepatic explants (3), 8 of 10 patients showed recurrence of cholangiocarcinoma at a median time of 26 months (95% confidence interval 13%–37%). All of the tumors were stage I or II at the time of OLT, and no patient received adjuvant treatment. They found a median time to death of 30 months (95% confidence interval 28%–53%) and a 3-year survival of only 30%.

There are reports of only 8 patients with BA and malignant tumors who underwent OLT (Table 1) (4–8). Overall, these patients had a recurrence rate of 12.5% after a median follow-up of 25.5 months; as opposed to those with incidental cholangiocarcinoma (5), who had a recurrence rate of 80% after a median follow-up of 28 months.



In conclusion, we reported a case of an incidental cholangiocarcinoma complicating an OLT for BA. The present case supports the broadly quoted but poorly corroborated notion that BA is associated with cholangiocarcinoma. Furthermore, it provides the first available evidence of OLT for cholangiocarcinoma in the setting of BA, and it attests to the poor prognosis associated with cholangiocarcinoma even when diagnosed at an early stage.

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