OVERVIEW

What is cholangiocarcinoma?

Cholangiocarcinoma, also known as bile duct cancer, is a malignant tumor originating from the epithelial cells of the bile ducts. Based on anatomical location, the human bile ducts can be divided into intrahepatic bile ducts, hilar bile ducts, and distal bile ducts. Accordingly, cholangiocarcinoma is classified into three types: intrahepatic cholangiocarcinoma, hilar cholangiocarcinoma, and distal cholangiocarcinoma.

Is cholangiocarcinoma common?

Cholangiocarcinoma accounts for about 3% of all gastrointestinal malignancies, with a prevalence of 0.01% to 0.46% in autopsy studies.

For unknown reasons, over the past 20 years, the incidence of intrahepatic cholangiocarcinoma has been increasing in Europe, North America, Asia, Japan, and Australia (excluding Denmark), while the incidence of extrahepatic cholangiocarcinoma has been declining worldwide.

Which regions globally have a high incidence of cholangiocarcinoma?

• The highest incidence of cholangiocarcinoma occurs in Southeast Asia (including Guangdong, Guangxi, and Hainan in China). The primary reason is that this region is endemic for liver fluke infections, and locals often consume raw or undercooked fish, leading to a much higher prevalence of liver fluke infections compared to other regions globally. Liver fluke infection is a high-risk factor for cholangiocarcinoma.

• Next, East Asia (including most parts of China, Japan, and South Korea) also has a high incidence, mainly due to the high prevalence of gallstones in the region. Long-term irritation of the bile ducts by biliary stones, leading to chronic subclinical cholangitis, may be a risk factor for malignant tumors.

• Additionally, both East and Southeast Asia are high-incidence regions for chronic viral hepatitis, primarily hepatitis B and hepatitis C.

SYMPTOMS

What are the typical symptoms of cholangiocarcinoma patients?

• Extrahepatic cholangiocarcinoma: Symptoms usually appear when the tumor obstructs the biliary drainage system.

• Symptoms caused by biliary obstruction include jaundice, pruritus, clay-colored stools, and dark urine.

• Other common symptoms include abdominal pain (30%-50%), weight loss (30%-50%), and fever (up to 20%). The abdominal pain is often described as a persistent dull ache in the right upper quadrant.

• Patients may also experience malaise, fatigue, and night sweats.

• In rare cases, cholangitis may occur.

• Cholangiocarcinoma involving only the intrahepatic bile ducts: Patients are less likely to develop jaundice but often have a history of dull right upper quadrant pain, weight loss, and elevated alkaline phosphatase levels. Some patients may be asymptomatic.

CAUSES

What are the risk factors for cholangiocarcinoma?

Currently, primary sclerosing cholangitis (an autoimmune disease affecting the bile ducts), fibropolycystic liver disease (such as choledochal cysts), biliary stones, liver fluke infection, and chronic viral hepatitis are considered high-risk factors for cholangiocarcinoma.

Additionally, two genetic disorders (Lynch syndrome and biliary papillomatosis) can also increase the risk of developing cholangiocarcinoma.

DIAGNOSIS

What tests should individuals suspected of having cholangiocarcinoma undergo?

• The diagnosis of cholangiocarcinoma heavily relies on imaging examinations such as ultrasound, CT, and MRI, which can reveal bile duct dilation upstream of the tumor, tumor location, and signs of vascular invasion caused by cholangiocarcinoma.

• Initial tests typically include contrast-enhanced MRI/magnetic resonance cholangiopancreatography (MRCP) or multiphase contrast-enhanced multidetector computed tomography (MDCT).

• Imaging findings vary by tumor location:

• Distal extrahepatic cholangiocarcinoma: Intrahepatic and extrahepatic bile duct dilation. A sudden change in bile duct diameter may be observed.

• Perihilar cholangiocarcinoma: Intrahepatic bile duct dilation with normal extrahepatic bile duct diameter.

• Intrahepatic cholangiocarcinoma: Mass-forming lesions, usually in a non-cirrhotic liver.

Can cholangiocarcinoma be diagnosed based on elevated tumor markers in the blood?

Among commonly used tumor markers, abnormal elevation of carbohydrate antigen 19-9 (CA19-9) is known to correlate with cholangiocarcinoma. However, similar to other malignancies, elevated CA19-9 does not definitively indicate cholangiocarcinoma. Other biliary conditions, such as choledocholithiasis or acute/chronic cholangitis, may also cause a sharp rise in CA19-9, while many cholangiocarcinoma patients show no increase in CA19-9 levels.

Therefore, blood tumor markers serve only as a reference to alert physicians, patients, and families to the possibility of malignancy and cannot be used alone for definitive diagnosis.

TREATMENT

Which department should be consulted for cholangiocarcinoma?

Cholangiocarcinoma is a relatively rare malignant tumor, and standardized diagnosis and treatment consensus has not yet been established. However, the academic community generally agrees that radical surgery (complete tumor resection with routine lymph node dissection) and postoperative adjuvant therapies (such as radiotherapy, chemotherapy, and immunotherapy) are the most critical factors for achieving a cure and prolonging survival. Patients are advised to seek treatment from experienced surgeons in high-level medical centers, such as general surgery, hepatobiliary surgery, or hepatopancreatobiliary surgery departments.

How is the surgical approach for cholangiocarcinoma selected?

The surgical approach for cholangiocarcinoma should be determined based on factors such as tumor location, extent of liver involvement, and whether major blood vessels are invaded. The procedure may require resection of the extrahepatic bile ducts, affected liver tissue, and hilar lymph nodes. Patients with distal cholangiocarcinoma may need to undergo pancreaticoduodenectomy, which involves removing the extrahepatic bile ducts, gallbladder, duodenum, part of the pancreas, stomach, and small intestine.

After resection of the relevant organs, gastrointestinal, biliary-enteric, and pancreaticoenteric anastomoses are performed to reconstruct pathways for food passage and digestive fluid secretion.

In summary, cholangiocarcinoma surgery is highly traumatic, technically demanding, and carries a significant risk of postoperative complications, requiring advanced surgical skills and comprehensive hospital capabilities.

Can all cholangiocarcinoma cases be treated surgically?

When patients present with obvious symptoms such as jaundice and weight loss and are diagnosed with cholangiocarcinoma, approximately 60% are already in advanced stages and have lost the opportunity for radical surgery.

Therefore, early diagnosis of cholangiocarcinoma has long been a research focus in clinical medicine.

What treatment options are available for cholangiocarcinoma patients who cannot undergo surgery?

• Patients may receive radiotherapy, chemotherapy, or newer treatments such as targeted therapy and immunotherapy.

• To relieve jaundice, minimally invasive palliative procedures such as percutaneous biliary drainage, biliary stent placement, or biliary-enteric anastomosis can be performed to address the issue of bile obstruction and impaired digestion.

DIET & LIFESTYLE

What is the treatment efficacy for cholangiocarcinoma?

Previously, the prognosis of this disease was considered poor, with most patients experiencing recurrence and metastasis within 1–2 years after radical surgery.

This is mainly because the disease is often diagnosed at an advanced stage, with possible lymph node or intrahepatic metastasis, peritoneal dissemination, or even micrometastases in other organs, significantly reducing surgical efficacy. However, with increased health awareness and the widespread use of imaging techniques such as CT and MRI, the early diagnosis rate of cholangiocarcinoma is expected to rise markedly. Combined with comprehensive postoperative therapy, more patients will achieve radical cure or significantly prolonged survival.

For inoperable patients or those with postoperative recurrence, previous literature reported a survival period of 6–9 months. However, recent advancements in chemotherapy, radiotherapy, targeted therapy, and immunotherapy have significantly extended survival for these patients. Some highly treatment-responsive cases even achieve tumor downstaging, making radical surgery possible.

What promising advancements exist in cholangiocarcinoma treatment?

Cholangiocarcinoma was once considered a rare malignancy with extremely poor outcomes. However, with global aging and improved diagnostic and therapeutic standards, its incidence is now recognized as higher than previously thought, and the prognosis is no longer as bleak.

Thorough radical surgery and standardized adjuvant therapy have become widely accepted approaches to improving efficacy, though disparities in healthcare levels mean this concept still requires broader implementation.

The advent of precision medicine has provided cancer patients with additional options beyond traditional treatments, such as targeted therapy and immunotherapy. The application of these therapies in cholangiocarcinoma is a major research focus, and increasingly encouraging results are anticipated.

PREVENTION

Can Cholangiocarcinoma Be Prevented?

• Avoid consuming undercooked foods such as raw fish and oysters to prevent liver fluke infections. For those already infected, completing a full course of deworming treatment as prescribed by a doctor is one of the most effective measures to prevent cholangiocarcinoma.

• Due to the complex and unclear mechanisms behind gallstone formation, preventing cholangiocarcinoma by avoiding gallstones is currently not feasible. However, patients with gallstones are advised to undergo regular ultrasound examinations (1–2 times per year).