Cholangiocarcinoma

• Talia Zenlea, M.D.
• Nadia Griller, M.D.

 Basic Information

Definition

Cholangiocarcinoma is a cancer that originates from the epithelial lining of bile ducts. Most commonly an adenocarcinoma, this tumor is classified based on its location within the biliary tree as intrahepatic, perihilar, or extrahepatic.

Synonyms

1. Bile duct carcinoma

ICD-10CM CODES
C22.1	Intrahepatic bile duct carcinoma
C24.0	Malignant neoplasm of extrahepatic bile duct

Epidemiology & Demographics

Incidence

1. •

   The incidence rate of cholangiocarcinoma varies by region. A low rate of 1-2 per 100,000 occurs in the United States, while incidence peaks at 80 per 100,000 in Thailand.

2. •

   Incidence rate of intrahepatic cholangiocarcinoma appears to be increasing.

3. •

   Higher incidence in Hispanic and Asian populations

Predominant Sex and Age

1. •

   Slightly more common in men

2. •

   Most often diagnosed between 50 and 70 years of age

3. •

   Patients with primary sclerosing cholangitis (PSC) can present as early as 30 years old

Risk factors

1. •

   PSC causes inflammation of the bile ducts leading to fibrosis and stricturing of the biliary tree. PSC is the most common risk factor for development of cholangiocarcinoma, with a lifetime risk of up to 15%

2. •

   Other risk factors include infection with hepatitis B and C, liver cirrhosis, chronic hepatolithiasis, choledochal cysts, and parasitic infections of the liver.

Physical Findings & Clinical Presentation

1. •

   With early-stage cholangiocarcinoma, the patient may be completely asymptomatic, and diagnosis is made incidentally on imaging or during the workup for elevation of liver enzymes.

2. •

   Later-stage cholangiocarcinoma may present as biliary obstruction.

3. •

   The clinical presentation is also dependent on the location of the tumor. Cholangiocarcinoma involving the intrahepatic ducts tends to cause nonspecific symptoms of dull, aching right upper quadrant pain and weight loss. A tumor of the extrahepatic ducts most often causes symptoms of biliary obstruction including jaundice, pale stools, and dark urine.

4. •

   Findings on physical examination may include jaundice, pain on palpation of the right upper quadrant, hepatomegaly, and fever.

Diagnosis

Differential Diagnosis

The differential diagnosis includes other conditions that may cause right upper quadrant pain, fever, and symptoms of biliary obstruction or those that present with a mass on imaging.

1. •

   Primary sclerosing cholangitis

2. •

   Choledocholethiasis

3. •

   Acute cholangitis

4. •

   Liver metastases

5. •

   Pancreatic head cancer

Workup

Fig. E1 describes an algorithm for the diagnosis of intrahepatic cholangiocarcinoma. The approach to the diagnosis of perihilar cholangiocarcinoma is summarized in Fig. E2. The Bismuth-Corlette classification of cholangiocarcinoma based on location is illustrated in Fig E3.

Laboratory Tests

1. •

   Liver enzymes

2. •

   INR

3. •

   Bilirubin

Blood work may reveal an “obstructive pattern” with predominant elevation of alkaline phosphatase and bilirubin.

Tumor markers

1. •

   CEA

2. •

   CA19-9

It is important to note that these tumor markers may be elevated even in the setting of benign inflammation of the biliary tree, for example, during an episode of acute cholangitis. These markers are neither sensitive nor specific for cholangiocarcinoma, but if they are elevated at the time of diagnosis, they may be helpful in tracking response to therapy or in monitoring for disease recurrence.

Imaging Studies

Abdominal ultrasound (Fig. E4)

1. •

   Initial test of choice in patients presenting with nonspecific symptoms of obstruction or elevated liver enzymes.

CT scan/magnetic resonance cholangiopancreatography (MRCP)

1. •

   Improved visualization of the biliary tree to allow for identification of the tumor, level of obstruction, and extent of disease.

Endoscopic retrograde cholangiopancreatography (ERCP) (Fig. E5)

1. •

   Can be used to obtain brushings or biopsies of the biliary tree, but diagnostic yield is poor, and there is a risk of cholangitis in patients with significant obstruction of bile drainage.

Endoscopic ultrasound (EUS)

1. •

   Allows fine-needle aspiration of distal biliary duct tumors and involved lymph nodes.

Treatment

Acute General Rx

1. •

   The only curative treatment option for cholangiocarcinoma is surgical extirpation. Eligibility for surgical resection with curative intent is based both on the location of the tumor and the stage of disease. Box E1 summarizes criteria for unresectability of perihilar cholangiocarcinoma.

   BOX E1Criteria for Unresectability of Perihilar Cholangiocarcinoma

   1. 1.

      Atrophy of one liver lobe with encasement of the contralateral portal vein branch

   2. 2.

      Atrophy of one liver lobe with contralateral secondary biliary radical involvement

   3. 3.

      Bilateral portal vein branch encasement

   4. 4.

      Bilateral hepatic artery encasement

   5. 5.

      Distant lymph node metastases

   6. 6.

      Hilar cholangiocarcinoma, Bismuth-Corlette type IV

   7. 7.

      Intrahepatic or distant metastases

   8. 8.

      Primary sclerosing cholangitis

   9. 9.

      Significant comorbid conditions

   From Feldman M et al [eds]: Sleisenger and Fordtran’s gastrointestinal and liver disease, ed 10, Philadelphia, 2016, Saunders.

2. •

   Surgical approaches include partial liver resection, pancreaticoduodenectomy, pancreaticojejunostomy, or even liver transplantation in carefully selected patients.

3. •

   Adjuvant chemotherapy, gemcitabine and cisplatin, has been shown to reduce mortality in patients with both positive margins post-resection and/or involved lymph nodes.

4. •

   The use of adjuvant radiation remains an area of controversy, but there is evidence of improved survival in inoperable patients with localized disease.

5. •

   In the setting of biliary obstruction, stenting or percutaneous drain insertion should be performed to facilitate bile flow and avoid stasis.

Disposition

1. •

   Surveillance imaging for recurrence is recommended every 6 months for a total of 2 years.

2. •

   Recurrence can occur locally or as metastatic disease, most commonly to liver, lung, or peritoneum.

3. •

   Five-year survival rates vary between 15% and 60% based on the stage of disease. Unfortunately, even those patients with node-negative disease who undergo resection with curative intent have a high rate of disease recurrence.

Referral

Referral should be made to a hepatobiliary surgeon for consideration of surgical resection and to a medical oncologist for possible adjuvant chemotherapy.

Suggested Readings

• V. Hrad, et al.: Risk and surveillance of cancers in primary biliary tract disease. Gastroenterol Res Pract. 2016 3432640

• M.W. Jackson, et al.: Treatment selection and survival outcomes with and without radiation for unresectable localized intrahepatic cholangiocarcinoma. Cancer J. 22:237 2016 27441741

• S. Onda, et al.: EUS-guided FNA for biliary disease as first-line modality to obtain histological evidence. Therap Adv Gastroenterol. 9:302 2016 27134660

• N. Razumilava, G.J. Gores: Cholangiocarcinoma. Lancet. 383:2168–2179 2014 24581682

• M. Squadroni, et al.: Cholangiocarcinoma. Crit Rev Oncol Hematol. 116:11–31 2017 28693792

• J.W. Valle, et al.: Biliary cancer: ESMO clinical practice guidelines. Ann Oncol. 27 (Suppl 5):v28–v37 2016 27664259

Related Content

1. Primary Sclerosing Cholangitis (Related Key Topic)