Cholangiocarcinoma

Content of This Page

1- Introduction

2- Pathophysiology

3- Symptoms

4- Stages of The Disease

5- Investigations

6- Treatment

7- What Should You Avoid

Introduction

Cholangiocarcinoma (CCA) is a rare and aggressive cancer arising from the epithelial cells of the bile ducts. It can occur anywhere along the biliary tree:

  • Intrahepatic (20–25%) – within the liver

  • Perihilar (50–60%) – at the junction of right and left hepatic ducts (also called Klatskin tumours)

  • Distal (20%) – lower bile duct near the pancreas

 

Although it makes up only 1.5% of all cancers, its incidence is increasing, particularly in regions with specific risk exposures.

© image from Wikimedia Commons

Pathophysiology

  1. Chronic Biliary Inflammation

    • Triggered by conditions such as:

      • Primary sclerosing cholangitis (PSC)

      • Choledochal cysts

      • Liver fluke infection (Clonorchis sinensis)

      • *Gallstones and biliary strictures

    • Inflammatory damage leads to cycles of injury and repair, promoting:

      • Biliary epithelial hyperplasia

      • Dysplasia (pre-cancerous change)

      • Genetic and epigenetic alterations in key signalling pathways

  1. Genetic Mutations and Dysplasia

    • Chronic injury fosters mutations in oncogenes and tumour suppressor genes (not detailed in Davidson).

    • Biliary dysplasia progresses through:

      • Low-grade → high-grade → invasive adenocarcinoma

  1. Local Invasion and Spread

    • Tumours commonly show:

      • Perineural invasion (into nerves)

      • Lymphatic and vascular infiltration

    • Aggressive local growth causes bile duct obstruction (leading to jaundice) and early metastasis.

© image from Wikimedia Commons

Symptoms

1-Painless obstructive jaundice – most common symptom (especially in perihilar/distal types).
2-Right upper quadrant (RUQ) pain – due to local tumour invasion.
3-Weight loss and fatigue – common systemic features.
4-Dark urine, pale stools, pruritus – signs of bile duct obstruction.
5-Less common: fever (with cholangitis), palpable gallbladder, hepatomegaly.

Stages of The Disease

1. Anatomical Subtypes (Not Formal Staging):

  • Intrahepatic: Within liver bile ducts

  • Perihilar (Klatskin tumours): At the bile duct confluence

  • Distal: Near the pancreas/common bile duct

2. Clinical Progression Stages (Implied):

StageFeatures
LocalisedTumour confined to bile ducts, resectable in ~20% of cases
Locally AdvancedInvasion of lymphatics, perineural tissues, adjacent organs or vessels
UnresectableWidespread local disease or multifocal liver involvement
MetastaticDistant spread (e.g. liver, peritoneum, lungs)

Key Prognostic Notes

  • Surgical resection offers 5-year survival of 20–40%, but is only possible in a minority.

  • Palliation with stenting or chemotherapy is used for unresectable stages.

Investigations

1-Blood Tests:

  • Liver function tests show cholestasis (↑ ALP, bilirubin)
  • CA 19-9 may be elevated but is not specific

2-Imaging:

  • MRCP: Best non-invasive biliary imaging
  • CT/MRI: Assess tumour extent and staging
  • EUS + FNA: For sampling suspicious masses or lymph nodes

3-Biliary Sampling:

  • ERCP with brush cytology: Allows diagnosis and drainage
  • Cholangioscopy: Direct biopsy in specialist centres

4-Histology:

  • Biopsy may not be needed if imaging is typical
  • Avoid percutaneous biopsy in surgical candidates (risk of tumour seeding)

Treatment

1-Surgical Resection:

  • Only curative option, but feasible in ~20% of cases
  • Involves bile duct and possible liver resection with biliary reconstruction
  • 5-year survival: 20–40%

2-Liver Transplantation:

  • Generally not recommended
  • Considered only in selected perihilar cases with neoadjuvant therapy

3-Palliative Biliary Drainage:

  • For unresectable cases with jaundice
  • Via endoscopic or percutaneous stents

4-Chemotherapy:

  • For advanced/unresectable cases
  • Common regimen: gemcitabine + cisplatin

5-Radiotherapy / Chemo-radiotherapy:

  • Used in select cases for local control

6-Photodynamic Therapy (PDT):

  • Palliative option in extrahepatic tumours to relieve obstruction

What Should You Avoid

1. Delayed Diagnosis

  • Avoid assuming jaundice is benign; early imaging (MRCP, CT) is essential to detect resectable disease.

2. Percutaneous Biopsy in Surgical Candidates

  • Avoid percutaneous liver or bile duct biopsy in patients with potentially resectable disease.

    • Risk: tumour seeding along the biopsy tract

    • Use EUS-guided FNA or ERCP-based sampling instead.

3. Unnecessary Surgery in Unresectable Cases

  • Avoid exploratory surgery unless full staging confirms operability.

    • Many patients present with advanced disease and won’t benefit from resection.

4. Inappropriate Use of Tumour Markers Alone

  • Avoid over-reliance on CA 19-9

    • It can be falsely elevated in benign cholestasis and lacks specificity.

5. Ineffective or Risky Herbal Therapies

  • Avoid unverified alternative treatments that may harm liver function or delay proper care.

6. Skipping Biliary Drainage in Obstructive Jaundice

 

  • Avoid leaving obstructed bile ducts untreated—can lead to infection and liver failure.

    • Use endoscopic or percutaneous drainage when needed.

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