Liver and Biliary Tract Tumors for the ABIM
Liver and Biliary Tract Tumors
Liver Tumors
- Hepatocellular Carcinoma (HCC):
- Epidemiology:
- The most common primary liver cancer, accounting for 80-90% of primary liver tumors.
- Strongly associated with chronic liver disease such as cirrhosis from hepatitis B, hepatitis C, alcoholic liver disease, and nonalcoholic steatohepatitis (NASH).
- Hepatitis B carries a direct oncogenic risk, even without cirrhosis, whereas hepatitis C usually leads to HCC through cirrhosis.
- Risk Factors:
- Chronic hepatitis infections (HBV, HCV), alcohol use, NASH, aflatoxin exposure, and genetic conditions such as hereditary hemochromatosis.
- Metabolic syndromes, including diabetes and obesity, are also linked to HCC development.
- Pathogenesis:
- Repeated liver injury and regeneration from chronic inflammation lead to DNA damage and mutations in oncogenes and tumor suppressor genes (e.g., TP53).
- Clinical Presentation:
- Often asymptomatic in early stages.
- Symptoms include weight loss, abdominal pain, jaundice, and ascites in advanced disease.
- Common signs include hepatomegaly, an abdominal mass, or decompensated cirrhosis.
- Diagnosis:
- Imaging: Multiphasic CT scan or MRI with characteristic arterial enhancement and delayed washout in the venous phase is diagnostic.
- Alpha-fetoprotein (AFP): Elevated in 50-70% of cases, used as a tumor marker for diagnosis and monitoring.
- Biopsy is rarely needed if imaging is definitive.
- Staging:
- Staging systems include Barcelona Clinic Liver Cancer (BCLC) and TNM, taking into account tumor size, vascular invasion, and liver function (Child-Pugh score).
- Treatment:
- Curative options for early-stage disease include surgical resection, liver transplantation, or radiofrequency ablation (RFA).
- Transarterial chemoembolization (TACE) is used for intermediate disease.
- Systemic therapy: Sorafenib, a tyrosine kinase inhibitor, is used in advanced HCC. Newer agents include lenvatinib, atezolizumab, and nivolumab for immune checkpoint inhibition.
- Prognosis:
- Prognosis depends on stage at diagnosis and liver function. Early-stage HCC treated with resection or transplant has a 5-year survival rate of 50-70%.
- Hepatic Adenoma:
- Epidemiology:
- Benign liver tumor, more common in young women due to oral contraceptive use.
- Associated with anabolic steroid use and glycogen storage diseases.
- Clinical Presentation:
- Often asymptomatic, but large adenomas (>5 cm) may cause abdominal pain or rupture, leading to hemorrhage.
- Diagnosis:
- Imaging: MRI with gadolinium is preferred, showing hypervascularity and a central scar.
- Biopsy is indicated when imaging is inconclusive.
- Treatment:
- Discontinuation of oral contraceptives is first-line.
- Surgical resection is recommended for symptomatic, large (>5 cm), or beta-catenin–activated adenomas due to risk of malignant transformation.
- Focal Nodular Hyperplasia (FNH):
- Epidemiology:
- Benign liver lesion, second only to hepatic hemangiomas, often found incidentally in women.
- Not associated with oral contraceptive use or malignant transformation.
- Clinical Presentation:
- Typically asymptomatic.
- Diagnosis:
- Imaging: MRI shows a central scar with contrast enhancement.
- Treatment:
- No treatment is required unless symptomatic, as there is no risk of malignancy.
- Hepatic Hemangioma:
- Epidemiology:
- The most common benign liver tumor, often discovered incidentally.
- Typically occurs in women and remains asymptomatic.
- Clinical Presentation:
- Usually asymptomatic but can cause abdominal pain or compression of nearby structures when large.
- Diagnosis:
- Ultrasound or MRI shows characteristic findings of a well-demarcated lesion with slow contrast filling.
- Treatment:
- Observation is generally recommended unless symptomatic.
Biliary Tract Tumors
- Cholangiocarcinoma:
- Epidemiology:
- Cancer of the bile ducts, accounting for 3% of all gastrointestinal cancers.
- Two major types: intrahepatic and extrahepatic cholangiocarcinoma (including Klatskin tumors).
- Risk Factors:
- Chronic biliary inflammation from primary sclerosing cholangitis (PSC), liver fluke infections (e.g., Clonorchis sinensis), choledochal cysts, and chronic hepatitis B or C infections.
- Clinical Presentation:
- Painless jaundice is the hallmark symptom of extrahepatic cholangiocarcinoma.
- Other signs include pruritus, dark urine, pale stools, and weight loss.
- Intrahepatic cholangiocarcinoma presents with vague symptoms like abdominal pain and hepatomegaly.
- Diagnosis:
- Imaging: MRI/MRCP or CT scan identifies biliary obstruction and tumor extent.
- CA 19-9: A tumor marker often elevated but not specific to cholangiocarcinoma.
- Biopsy is required to confirm the diagnosis.
- Staging:
- TNM staging is based on tumor location, bile duct involvement, lymph node status, and distant metastasis.
- Treatment:
- Surgical resection is the only curative option but is limited to early-stage disease.
- Liver transplantation may be considered for select patients with early-stage hilar cholangiocarcinoma.
- Adjuvant chemotherapy (e.g., gemcitabine, cisplatin) is often used postoperatively.
- Palliative options include biliary stenting to relieve obstruction in advanced disease.
- Prognosis:
- The prognosis is poor, with a 5-year survival rate of less than 10% in advanced stages.
- Gallbladder Cancer:
- Epidemiology:
- Rare, but the most common malignancy of the biliary tract.
- Associated with chronic cholecystitis, gallstones, and porcelain gallbladder.
- More common in women and individuals of Native American descent.
- Risk Factors:
- Gallstones, chronic gallbladder inflammation, and choledochal cysts.
- Clinical Presentation:
- Often asymptomatic in early stages, with symptoms appearing late.
- When symptomatic, patients present with right upper quadrant pain, jaundice, weight loss, and a palpable gallbladder (Courvoisier sign).
- Diagnosis:
- Ultrasound or CT scan detects gallbladder masses.
- Biopsy is performed for confirmation.
- Treatment:
- Surgical resection is the primary treatment for localized disease, but it is often detected late.
- Adjuvant chemotherapy or radiation may be used in advanced disease.
- Prognosis:
- Gallbladder cancer has a poor prognosis, with a 5-year survival rate of less than 10% in advanced disease.
Key Points
- Hepatocellular carcinoma (HCC) is the most common primary liver malignancy, with cirrhosis from hepatitis B, C, and NASH as major risk factors. Early-stage disease may be treated with resection or liver transplantation, while systemic therapy is used for advanced cases.
- Hepatic adenoma is linked to oral contraceptive use and requires surgical resection if large or symptomatic, due to the risk of rupture or malignant transformation.
- Cholangiocarcinoma, a cancer of the bile ducts, presents with painless jaundice and has a poor prognosis. Early-stage disease may benefit from surgical resection or liver transplantation.
- Gallbladder cancer is associated with chronic gallbladder inflammation and gallstones, with poor outcomes due to late-stage diagnosis.
- Imaging techniques like CT, MRI, and tumor markers (e.g., AFP for HCC, CA 19-9 for cholangiocarcinoma) are crucial for diagnosis and staging of liver and biliary tract tumors.