Skip to content

Biliary Tract Tumors

Biliary Tract Tumors Revision Notes

Benign Gallbladder Tumors

Types of Benign Tumors

  • Epithelial Tumors
    • Adenomas
      • Account for approximately 4% of gallbladder polyps.
      • Thought by some to be neoplastic.
      • Most gallbladder cancers do not arise from precursor adenomas.
  • Mesenchymal Tumors
    • Fibromas
    • Lipomas
    • Hemangiomas
  • Pseudotumors
    • Cholesterol Polyps
      • Most common benign gallbladder tumor (≈60% of polyps).
    • Inflammatory Polyps
    • Adenomyomas
      • Make up about 25% of gallbladder polyps.
      • Can appear polypoid or infiltrative.
      • Associated with biliary colic–like symptoms.

Clinical Presentation

  • Varies Widely
    • Many polyps are found incidentally during imaging for unrelated issues.
    • Symptoms may include:
      • Abdominal pain.
      • Liver function test abnormalities.
      • Biliary colic–like symptoms (especially with adenomyomas).

Risk of Malignancy

  • Increases with:
    • Polyp Size
      • Polyps ≥1 cm have a higher risk.
    • Solitary Polyps
      • Multiple small polyps are less suspicious.
  • Associated Factors:
    • Age >50 years
    • Primary Sclerosing Cholangitis
    • Congenital Polyposis Syndromes
    • Chronic Hepatitis B

Management

  • Cholecystectomy Indications:
    • Symptomatic Patients
      • Any symptoms referable to gallbladder polyps warrant surgery.
    • Suspicious Polyps
      • Size >10 mm
      • Number <3
      • Sessile Lesions
      • Sonographic Evidence of Mucosal Invasion
  • Surgical Considerations:
    • Laparoscopic Cholecystectomy
      • Acceptable but minimize risk of tumor spillage.
    • Intraoperative Frozen-Section Analysis
      • Recommended if there's a high suspicion of malignancy.
      • Confirmation of cancer may require an extended oncologic resection.
  • Non-Surgical Management:
    • Close Radiographic Follow-Up
      • For borderline polyps not undergoing surgery.
      • Serial ultrasounds every 6–12 months to monitor for rapid growth.

Gallbladder Cancer

Overview

  • Most Common Biliary Malignancy
  • Fifth Most Common Gastrointestinal Cancer
  • Aggressive Nature
    • Propensity for:
      • Nodal metastases.
      • Direct hepatic invasion.
      • Seeding of peritoneal surfaces.
  • Poor Prognosis
    • Median survival <6 months.
    • Possibility of cure exists for a subset of patients.

Epidemiology

  • Incidence Varies Geographically
    • Highest: South America, Delhi (up to 22 per 100,000 women).
    • Intermediate: Europe.
    • Lower: United States and United Kingdom (1–2 per 100,000).
  • Risk Factors:
    • Chronic Gallbladder Irritation and Inflammation
      • History of biliary disease.
      • Mirizzi Syndrome
        • Compression of the common hepatic duct by a gallstone in the gallbladder neck or cystic duct.
      • Porcelain Gallbladder
        • Calcification of the gallbladder wall due to chronic inflammation.
        • Cancer incidence in porcelain gallbladder is 7–25%.
    • Demographics and Lifestyle:
      • Age (more common in older individuals).
      • Female Gender
      • Obesity
      • High Carbohydrate Diet
      • Ethanol and Tobacco Abuse
    • Anomalous Pancreaticobiliary Duct Junction
      • Associated with choledochal cyst disease.

Anatomy Relevant to Gallbladder Cancer

  • Gallbladder Fossa
    • Located beneath hepatic segments IVB and V.
    • Implications for Surgery:
      • Tumors may require resection of these liver segments due to direct invasion.
  • Infundibulum Proximity
    • Adjacent to the right portal pedicle.
    • Advanced Tumors:
      • May invade the right portal pedicle.
      • Surgical Resection:
        • May necessitate a right trisectionectomy.
  • Gallbladder Wall Structure
    • Thin Wall
      • Composed of:
        • Inner mucosa.
        • Thin lamina propria.
        • Single muscularis layer (unlike other hollow organs with two layers).
    • Surgical Considerations:
      • Serosa is often opened during cholecystectomy.
      • Mucosal tumors can invade across the serosa, leading to positive margins.

Lymphatic Drainage

  • Primary Drainage:
    • Cystic [12c] and Pericholedochal [12b]Lymph Nodes
  • Secondary Drainage:
    • Hepatoduodenal Ligament Nodes
      • Posterior pancreaticoduodenal nodes. [13]
      • Periportal nodes. [12p]
      • Common hepatic artery nodes. [8]
  • No Ascending Drainage
    • No lymphatic flow into the liver hilum.
  • Surgical Importance:
    • Meticulous Lymphadenectomy in the hepatoduodenal ligament is critical.
    • Challenges:
      • Direct drainage to aortocaval nodes complicates complete removal of lymphatic metastases.

Pathology

  • Tumor Locations:
    • Fundus: ~60%.
    • Body: ~30%.
    • Neck: ~10%.
  • Types of Tumor Growth:
    • Infiltrative Tumors
      • Most common.
      • Indurate areas of wall thickening.
      • Spread into the subserosal plane.
    • Nodular Tumors
      • Invade adjacent structures.
      • Sharply defined borders.
    • Papillary Tumors
      • Grow polypoid into the lumen.
      • Minimal wall invasion.
      • Associated with better prognosis.
  • Histology:
    • Adenocarcinoma: Most common subtype.
    • Other Subtypes:
      • Adenosquamous carcinoma.
      • Oat cell carcinoma.
      • Sarcoma.
      • Carcinoid.
      • Lymphoma.
      • Melanoma.
  • Histologic Grading:
    • G1: Well-differentiated.
    • G4: Undifferentiated.
    • Most patients present with G3 (poorly differentiated) tumors.
  • Metastasis and Invasion:
    • Early penetration beyond the muscle layer.
    • Common Findings at Diagnosis:
      • Direct hepatic invasion (59%).
      • Lymph node metastases (45%).
      • Distant metastases (20%).

Mutations and Targeted Therapies

  • Limited Understanding of Carcinogenesis
    • Heterogeneous pathways lead to gallbladder cancer.
  • Identified Mutations:
    • BRAF Mutations in approximately 33% of specimens.
    • K-ras mutations less commonly associated.
  • Challenges in Targeted Therapy:
    • Lack of uniform mutations makes targeted therapy difficult.
    • Future Directions:
      • More research needed to understand mechanisms.
      • Potential for promising targeted therapies.

Diagnosis

Clinical Presentation

  • Symptoms Similar to Benign Biliary Colic
    • May delay diagnosis.
  • Advanced Disease Indicators:
    • Persistent Pain
    • Weight Loss
    • Anorexia
    • Jaundice
      • Associated with unresectable disease in 95% of jaundiced patients.
    • Palpable Right Upper Quadrant Mass

Tumor Markers

  • Carcinoembryonic Antigen (CEA)
    • >4 ng/mL suggests gallbladder cancer.
    • Sensitivity: 50%.
    • Specificity: 93%.
  • Carbohydrate Antigen (CA) 19-9
    • >20 U/mL indicates higher risk.
    • Sensitivity: 79.4%.
    • Specificity: 79.2%.

Imaging Studies

  • Ultrasound Findings:
    • Polypoid Gallbladder Mass (27% of cases).
    • Invasive Lesion (50% of cases).
    • Other Signs:
      • Discontinuous mucosa.
      • Echogenic mucosa.
      • Submucosal echolucency.
  • Computed Tomography (CT) Findings:
    • Mass Filling the Gallbladder Lumen (42%).
    • Polypoid Mass (26%).
    • Mass in Gallbladder Fossa without recognizable gallbladder (26%).
    • Diffuse Wall Thickening (6%).
    • Example Image: CT scan showing a mass in the gallbladder fossa.
  • Magnetic Resonance Imaging (MRI) and MRCP:
    • Excellent for detecting:
      • Small hepatic metastases.
      • Common bile duct involvement.

Challenges in Lymph Node Assessment

  • Difficulty Identifying Metastases Preoperatively
    • Enlarged nodes may be reactive rather than metastatic.
  • Imaging Limitations:
    • CT scans may miss metastatic nodes less than 10 mm.
    • PET scans useful for distant metastases but limited for nodes.
  • Endoscopic Ultrasound:
    • May help assess peripancreatic and periportal nodes.

Biopsy Considerations

  • Risk of Tumor Seeding
    • Percutaneous Core Biopsy: Higher risk of spreading cancer cells.
  • Fine-Needle Aspiration (FNA):
    • Lower risk of seeding.
    • Provides diagnostic material.
    • Used when surgery is not an option.
  • Bile Cytology:
    • Low sensitivity (~50%).
    • Not routinely helpful for diagnosis.

Summary

  • Benign gallbladder tumors are common and include cholesterol polyps, adenomyomas, and adenomas.
  • Risk factors for malignancy in gallbladder polyps include size ≥1 cm, solitary polyps, and patient age >50 years.
  • Gallbladder cancer is aggressive with poor prognosis but may be curable in early stages.
  • Risk factors for gallbladder cancer involve chronic inflammation, gallstones, and certain anatomical anomalies.
  • Diagnosis relies on imaging and tumor markers, but detection of metastases remains challenging.
  • Surgical management requires careful planning due to the gallbladder's anatomy and lymphatic drainage patterns.

Gallbladder Cancer Staging and Management Revision Notes

Staging

Overview

  • Tumor stage is the most accurate predictor of outcome in gallbladder cancer.
  • Advances in surgical therapy have evolved staging criteria.
    • Previous AJCC Staging: Tumors extending into the liver were considered unresectable Stage IV.
    • Current AJCC Staging: Tumors invading the liver are categorized as Stage III due to improved resection techniques.

AJCC Staging System (7th Edition)

Tumor (T) Classification

  • T1a: Tumor invades lamina propria of gallbladder wall.
  • T1b: Tumor invades muscular layer of gallbladder wall.
  • T2: Tumor invades perimuscular connective tissue but not across serosa.
  • T3: Tumor invades across serosa and/or into the liver or one adjacent organ.
  • T4: Tumor invades main portal vein or hepatic artery, or two or more extrahepatic structures.

Node (N) Classification

  • N0: No lymph node involvement.
  • N1: Lymph node involvement within the hepatoduodenal ligament. now changed to 1-3 Ln’s
  • N2: Lymph node involvement beyond the hepatoduodenal ligament. now changed to ≥ 4 regional

Metastasis (M) Classification

  • M0: No distant metastases.
  • M1: Presence of distant metastases.

Stages

  • Stage IA: T1 N0 M0
  • Stage II: T2 N0 M0
  • Stage IIIA: T3 N0 M0
  • Stage IIIB: T1-3 N1 M0
  • Stage IVA: T4 N0-1 M0
  • Stage IVB: T1-4 N2 M0 or T1-4 N0-2 M1

Importance of Lymphadenectomy

  • Thorough lymphadenectomy is crucial due to prognostic implications.
  • N1 Nodes: Cystic duct, common bile duct, hepatic artery, periportal lymph nodes.
  • N2 Nodes: Paraaortic, paracaval, superior mesenteric artery, and celiac lymph nodes.
  • Standard lymphadenectomy is limited to the hepatoduodenal ligament.
    • Complete clearance of N2 nodes is avoided to reduce morbidity.
  • Imaging Modalities: CT, MRI, and PET scans are essential for surgical planning and staging.

Stage I Gallbladder Cancer

  • Often discovered incidentally after routine cholecystectomy for presumed benign disease.
  • T1a Tumors:
    • Invade the lamina propria.
    • Simple cholecystectomy is usually curative.
    • Low likelihood of N1 disease.
  • T1b Tumors:
    • Invade the muscular layer.
    • Management is debated.
    • Up to 20% may have lymph node metastases.
    • Many advocate for radical resection.

Stage II Gallbladder Cancer

  • T2 Tumors:
    • Invade perimuscular connective tissue.
    • Simple cholecystectomy often results in margin positivity (40-50%).
    • Approximately 50% have nodal metastases.
  • Extended cholecystectomy with portal lymphadenectomy is recommended.
    • Results in 5-year survival rates of 70-90%.
    • Simple cholecystectomy alone results in 20-40% survival, with no survivors if margins are positive.

Stage III Gallbladder Cancer

  • T3 Tumors:
    • Invade across serosa and/or into liver or one adjacent organ.
  • Extended cholecystectomy improves survival (33-67% 5-year survival).
  • Tumors in the infundibulum may require:
    • Right hemiliver removal.
    • Resection of segment IVA.
    • Procedures like extended right hepatectomy or right trisectionectomy.

Stage IV Gallbladder Cancer

  • T4 Tumors or N2/M1 Disease.
  • No long-term survival observed.
  • Indicates aggressive tumor biology.
  • Involvement of N2 nodes or distant metastases signifies advanced disease.

Surgical Management

Radical (Extended) Cholecystectomy

  • Standard template for gallbladder cancer surgery.
  • Includes:
    • Cholecystectomy with en bloc resection of liver segments IVB and V.
    • Lymphadenectomy of cystic, pericholedochal, periportal, posterior pancreaticoduodenal, and local aortocaval lymph nodes.

Tailoring Surgical Therapy

  • Surgical approach depends on tumor stage and patient factors.
  • Lymphadenectomy may involve skeletonizing the porta hepatis.
  • Additional Procedures:
    • Resection of extrahepatic biliary system with Roux-en-Y hepaticojejunostomy may be necessary.
    • Especially in cases with:
      • Prior dissection.
      • Tumor extension into the common bile duct.
      • Obesity.

Incidentally Discovered Gallbladder Cancer

  • Often diagnosed after routine cholecystectomy.
  • If discovered during surgery:
    • Surgeon should discuss with patient's family.
    • Options:
      • Convert to open exploration for extended cholecystectomy.
      • Abort procedure for later reexploration or referral.
  • Minimally invasive resection may be possible at specialty centers.
  • Re-exploration Outcomes:
    • 66% eligible for re-exploration.
    • 62% underwent curative (R0) resections.
    • Presence of residual disease post-resection correlates with poor survival.

Adjuvant Therapy

Current Evidence

  • Gallbladder cancer is resistant to chemotherapy.
  • Radiation therapy effectiveness is limited due to diffuse peritoneal spread.
  • Studies show mixed outcomes with adjuvant therapy.
  • Phase III Trial Findings:
    • 5-FU/mitomycin improved 5-year overall survival (26% vs. 14%).
    • Improved 5-year disease-free survival (20% vs. 11%).
    • No benefit observed in other pancreaticobiliary malignancies.
  • Meta-analyses suggest a small survival benefit with radiotherapy.

Clinical Practice

  • Adjuvant therapy often offered to patients with:
    • Positive resection margins.
    • Nodal metastases.
  • No large randomized trials to establish definitive recommendations.

Palliation

Need for Palliative Care

  • High likelihood of surgical unresectability.
  • Median survival for unresectable disease: 2-4 months.
  • Goals:
    • Minimize morbidity.
    • Improve quality of life.

Methods of Palliation

  • Surgical Palliation:
    • Segment III biliary bypass for biliary decompression.
    • Avoids gallbladder and hepatic hilum.
  • Percutaneous Biliary Drainage:
    • Preferred in advanced disease with limited survival expectancy.
  • Resection of Port Site Recurrences:
    • Can alleviate pain and prevent complications from necrotic wounds.
  • Chemotherapy and Radiation:
    • No consistent benefit in palliation.

Surgical Technique for Gallbladder Cancer

Operative Strategy

  1. Exploratory Laparoscopy:
    • Assess for peritoneal or hepatic spread.
  2. Abdominal Exploration:
    • Through bilateral subcostal or right transverse incision.
  3. Lymphadenectomy:
    • Mobilize duodenal sweep with Kocher maneuver.
    • Harvest retroduodenal lymphatic tissue, including aortocaval and superior mesenteric nodes.
    • Skeletonize portal lymphatic tissue off extrahepatic biliary system.
    • May require excision of extrahepatic bile ducts in certain cases.

Hepatic Resection

  • Lower hilar plate by incising Glisson capsule at segment IVB base.
  • Determine extent of hepatic resection needed.
    • May involve extended right hemihepatectomy or right trisectionectomy.
  • Maintain low central venous pressure and Trendelenburg position during hepatectomy.
  • Inflow Control:
    • Segment IVB: Dissect umbilical fissure vessels.
    • Segment V: Control vessels during parenchymal transection.
  • Avoid Injury:
    • Middle hepatic vein between segments IVA and VIII.
  • Intraoperative Ultrasonography:
    • Aids in identifying vessel anatomy.

Reconstruction

  • If extrahepatic biliary resection performed:
    • Construct retrocolic Roux-en-Y hepaticojejunostomy.
  • Port Site Excision:
    • Optional removal of skin and fascia from laparoscopic port sites for staging.

Benign Biliary Tumors

Types of Benign Biliary Tumors

  • Common Benign Tumors:
    • Papillomas
    • Adenomas
  • Less Common Tumors:
    • Granular cell myoblastomas
    • Neural tumors
    • Endocrine tumors
    • Leiomyomas

Clinical Presentation

  • Often located near the ampulla of Vater or common bile duct.
  • Symptoms include:
    • Progressive or intermittent jaundice.
    • Similar to symptoms of malignant biliary obstruction.

Treatment

  • Local excision with removal of a portion of the duct wall.
  • Important to prevent local recurrences.

Specific Benign Tumors

Bile Duct Adenomas

  • Benign intrahepatic tumors.
  • Found incidentally during surgery.
  • Appearance:
    • Well-demarcated, white, subcapsular lesions.
    • Size ranges from a few millimeters to 1-2 cm.
  • Histology:
    • Well-differentiated bile duct structures with fibrous stroma.
  • Clinical Significance:
    • Generally asymptomatic.
    • Not proven to be precancerous.

Biliary Cystadenomas

  • Unusual benign tumors with multiloculated cystic appearance.
  • Types:
    • Mucinous cystadenomas (most common).
      • May be associated with pancreatic mucinous cystic neoplasms.
      • Associated with ovarian-like stroma in females.
    • Serous cystadenomas (less common).
  • Malignant Potential:
    • Occasional presence of dysplasia.
    • Potential to transform into biliary cystadenocarcinomas.

Differential Diagnosis of Obstructing Lesions

  • Primary Sclerosing Cholangitis:
    • Idiopathic, premalignant disorder.
    • Progressive biliary fibrosis.
    • Mimics malignant biliary disease on imaging.
  • Mirizzi Syndrome:
    • Impacted gallstone in gallbladder neck compresses common bile duct.
    • Causes pericholecystic inflammation and biliary obstruction.
  • Benign Idiopathic Focal Stenosis (Malignant Masquerade):
    • Benign fibroproliferative disorder.
    • Often involves hepatic duct confluence.
    • Indistinguishable from cholangiocarcinoma without surgery.

Summary

  • Tumor staging is crucial for prognosis and management of gallbladder cancer.
  • Extended cholecystectomy with lymphadenectomy is standard for stages beyond T1a.
  • Adjuvant therapy has limited evidence but is often considered for high-risk patients.
  • Palliative care focuses on symptom relief due to poor prognosis in unresectable cases.
  • Benign biliary tumors, though rare, require differentiation from malignant lesions and appropriate management.

Cholangiocarcinoma Revision Notes

Overview

  • Cholangiocarcinoma is an uncommon cancer arising from the biliary epithelium.
  • Accounts for 2% of all reported malignancies.
  • Incidence in the United States: 1–2 per 100,000.
  • Can develop anywhere along the biliary system.

Classification

  • Hilar Cholangiocarcinomas (40–60%)
    • Located at the liver hilum.
  • Distal Cholangiocarcinomas (20–30%)
    • Occur in the lower biliary tract.
  • Intrahepatic Cholangiocarcinomas (10%)
    • Also known as peripheral cholangiocarcinomas.
  • Diffuse or Multifocal (<10%)
    • Spread throughout the biliary system.

Epidemiology

  • Higher incidence among Native Americans and Japanese Americans.
  • Peak incidence in the eighth decade of life.
  • Men slightly more affected by intrahepatic cholangiocarcinoma.
  • Risk Factors:
    • Primary sclerosing cholangitis
    • Choledochal cyst disease
    • Chronic viral hepatitis (B and C)
    • Cirrhosis
    • Prior transduodenal sphincteroplasty
    • Chronic biliary parasitic infestations (e.g., Opisthorchis viverrini)
    • Exposure to thorotrast, asbestos, dioxin, nitrosamines

Pathology

Intrahepatic Cholangiocarcinoma

  • Gross Appearance:
    • Scirrhous lesions with non-encapsulated infiltrative growth.
    • Poorly defined tumor margins.
  • Histology:
    • Usually poorly differentiated adenocarcinoma.
    • Can be misdiagnosed as metastatic adenocarcinomas.
    • Variants include:
      • Papillary carcinoma
      • Signet ring cells
      • Squamous cells
      • Mucoepidermoid cells
      • Spindle cells

Hilar and Extrahepatic Cholangiocarcinoma

  • Macroscopic Subtypes:
    • Sclerosing (70%)
      • Circumferential ductal thickening.
      • Periductal fibrosis and inflammation.
      • Usually hilar in location.
    • Nodular (20%)
      • Firm tumors extending irregularly into the duct lumen.
    • Papillary (5–10%)
      • Soft, friable tumors projecting into the duct lumen.
      • Usually distal in location.
      • Associated with higher resectability and better outcomes.
  • Growth Pattern:
    • Longitudinal spread beneath normal ductal epithelium.
    • Requires careful microscopic examination of margins during surgery.
  • Desmoplastic Reaction:
    • Dense fibrotic stroma with small foci of malignant cells.
    • Makes needle biopsy challenging.
  • Perineural and Lymphovascular Spread:
    • Common, leading to hepatic atrophy.
    • Up to one-third present with nodal metastases.

Clinical Presentation

Intrahepatic Cholangiocarcinoma

  • Symptoms:
    • Nonspecific: Malaise, abdominal pain.
    • Jaundice is uncommon.

Hilar and Distal Cholangiocarcinoma

  • Symptoms:
    • Pain, anorexia, weight loss.
    • Pruritus (common, often precedes jaundice).
    • Jaundice due to biliary obstruction.
    • Abnormal liver enzymes.
  • Bilirubin Levels:
    • Malignant obstruction: >10 mg/dL (mean ~18 mg/dL).
    • Benign obstruction: 2–4 mg/dL, rarely >15 mg/dL.
  • Cholangitis:
    • Rare at presentation but can occur after biliary instrumentation.
  • Coexisting Conditions:
    • May coexist with benign gallstone disease.
  • Distal Cholangiocarcinoma:
    • Can mimic other periampullary neoplasms.
  • Hepatic Atrophy:
    • Indicative of chronic biliary obstruction (gradual) or portal obstruction (rapid).

Diagnosis

Laboratory Tests

  • Tumor Markers:
    • CA 19-9:
      • Levels >100 U/mL suggest cholangiocarcinoma.
      • Sensitivity: 89%, Specificity: 86%.
      • False Elevations: Occur with biliary obstruction; assess after decompression.
      • Lewis Antigen Non-producers: (~10% of patients) may have undetectable levels.
  • Other Tests:
    • CEA: To help differentiate from other malignancies.
    • Alpha-fetoprotein: To rule out hepatocellular carcinoma.
    • Viral Serologies: Hepatitis B and C.

Imaging Studies

  • Ultrasound:
    • Initial assessment.
    • Duplex ultrasonography evaluates biliary ductal and vascular involvement.
  • Computed Tomography (CT):
    • High-resolution, thin-section CT with arterial and portovenous phases.
    • Intrahepatic Cholangiocarcinoma:
      • Hypodense mass with irregular margins.
      • Peripheral rim enhancement in arterial phase.
      • Progressive hyperattenuation in venous and delayed phases.
  • Magnetic Resonance Imaging (MRI) and MRCP:
    • MRI:
      • Better delineates intrahepatic tumor extension.
      • Limited in vascular assessment.
    • MRCP:
      • Noninvasive biliary imaging.
      • Avoids complications of invasive procedures.
  • Endoscopic Retrograde Cholangiopancreatography (ERCP):
    • Useful for distal cholangiocarcinoma.
    • Allows for brushings and biliary cytology (low sensitivity).
  • Endoscopic Ultrasound (EUS):
    • Assesses small distal lesions.
    • Can obtain tissue samples.
  • PET Scan:
    • May detect distant metastases.
    • Not routinely recommended due to limited impact on management.

Biopsy and Histology

  • Challenges:
    • Desmoplastic reaction can lead to sampling errors.
    • Needle biopsies may be inconclusive.
  • Fluorescence In Situ Hybridization (FISH):
    • Aids diagnosis in conditions like primary sclerosing cholangitis.
    • Specificity: 93%, Sensitivity: 51%.
  • Preoperative Tissue Diagnosis:
    • Not always required if benign causes are excluded.
    • Avoid percutaneous/laparoscopic biopsies in potential transplant candidates.
  • Immunostains:
    • Differentiate from other adenocarcinomas or mixed tumors.
    • Essential for intrahepatic cholangiocarcinoma diagnosis.

Differential Diagnosis

  • Metastatic Adenocarcinoma:
    • Rule out primary tumors elsewhere (e.g., colorectal cancer).
  • Hepatocellular Carcinoma:
    • Differentiated via alpha-fetoprotein levels and imaging.
  • Benign Biliary Obstruction:
    • Gallstones, strictures.

Key Points

  • Late Presentation:
    • Most patients present with advanced disease not amenable to surgery.
  • Surgical Resection:
    • Only potential cure but feasible in a minority.
  • Imaging:
    • Critical for assessing resectability.
    • Cross-sectional imaging prior to biliary instrumentation is preferred.
  • Symptoms:
    • Often nonspecific, leading to delayed diagnosis.
  • Growth Pattern:
    • Insidious and longitudinal, making complete surgical removal challenging.
  • Importance of Margins:
    • Careful examination during surgery due to subepithelial spread.
  • Public Health Efforts:
    • Reduction of parasitic infestations (e.g., O. viverrini in Thailand) may decrease incidence over time.

Summary

Cholangiocarcinoma is a rare bile duct cancer with various subtypes based on location. Risk factors include chronic biliary diseases, parasitic infections, and exposure to certain chemicals. Diagnosis relies on imaging and tumor markers, but tissue diagnosis can be difficult due to the tumor's desmoplastic nature. Early detection is rare, and prognosis is generally poor due to late presentation and advanced disease at diagnosis.

Cholangiocarcinoma Staging & Management

Overview

  • Cholangiocarcinoma: A rare cancer of the bile ducts, accounting for 2% of all malignancies.
  • Incidence: 1–2 per 100,000 in the U.S.
  • Types based on location:
    • Hilar Cholangiocarcinoma (40–60%)
    • Distal Cholangiocarcinoma (20–30%)
    • Intrahepatic Cholangiocarcinoma (10%)
    • Diffuse or Multifocal (<10%)

Staging Systems

Bismuth-Corlette System

  • Anatomically based, focuses on the location of the tumor within the biliary tree.
  • Not highly predictive of patient outcomes.

AJCC Staging System (7th Edition)

  • Differentiates between hilar, intrahepatic, and distal cholangiocarcinoma.
  • Incorporates surgical resectability and prognostic factors.

  • Stages for Hilar Cholangiocarcinoma:

    • T1: Tumor confined to the bile duct.
    • T2: Tumor invades beyond the bile duct.
    • T3: Tumor invades unilateral branches of the portal vein or hepatic artery.
    • T4: Tumor invades main portal vein or hepatic artery or involves both lobes.

    image.png

Factors Influencing Prognosis

  • R0 Resection: Complete removal with negative margins is critical.
  • Other Factors:
    • Number of tumors.
    • Vascular invasion.
    • Lymph node metastases.
    • Nodal status is significant for survival.

Criteria for Unresectability (Box 112.1)

  • Medical Contraindications: Poor health, advanced cirrhosis, portal hypertension.
  • Anatomic Factors:
    • Bilateral second-order biliary radicle involvement.
    • Bilateral hepatic artery and/or portal venous branch involvement.
    • Main portal vein involvement or encasement.
    • Lobar atrophy with contralateral involvement.

  • Distant Disease:

    • N2 nodal involvement (beyond regional nodes).
    • Distant metastases.

    image.png

Surgical Management

Goal of Surgery

  • Achieve a complete R0 resection for potential cure.

Intrahepatic Cholangiocarcinoma

  • Surgical Approach:
    • Anatomic hepatic resection similar to other liver cancers.
  • Outcomes:
    • 5-year survival: 30–40%.
  • Predictors of Poor Survival:
    • Vascular invasion.
    • Positive margins.
    • Multiple tumors.
    • Large tumor size (>5 cm).
    • Regional nodal involvement.

Hilar Cholangiocarcinoma

  • Surgical Strategy:
    • Extrahepatic bile duct excision with partial hepatectomy.
    • Hepaticojejunostomy for biliary reconstruction.
  • Preoperative Assessment:
    • Laparoscopy can identify unresectable disease.
  • Importance of Partial Hepatectomy:
    • Improves chances of negative margins.
    • Caudate lobectomy often required due to tumor proximity.
  • Outcomes:
    • Margin-negative resection achievable in 70–80% of cases.
    • 5-year survival: 25–50%.
  • Predictors of Improved Survival:
    • Well-differentiated tumors.
    • Negative margins.
    • Concomitant hepatic resection.

Distal Cholangiocarcinoma

  • Surgical Approach:
    • Pancreaticoduodenectomy (Whipple procedure).
  • Clinical Presentation:
    • Similar to other periampullary tumors.
  • Outcomes:
    • Historically thought better than pancreatic cancer, but recent studies show no significant difference.

Orthotopic Liver Transplantation

  • Traditional Outcomes: Suboptimal survival rates.
  • Mayo Clinic Protocol:
    • Neoadjuvant chemoradiation followed by transplantation.
    • Eligibility Criteria:
      • Tumor ≤3 cm.
      • No metastases.
      • Unresectable but localized disease.
  • Results:
    • 5-year survival: 73%.
    • Better outcomes in patients with primary sclerosing cholangitis.

Adjuvant Therapy

Systemic Chemotherapy

  • Evidence Limited due to rare disease and heterogeneous studies.
  • ABC-02 Trial:
    • Cisplatin and gemcitabine vs. gemcitabine alone.
    • Median survival benefit: 11.7 vs. 8.1 months.

Locoregional Therapy

  • Rationale: High rate of locoregional recurrence.
  • Postoperative Chemoradiotherapy:
    • May improve locoregional control and survival.
    • Controversial, with mixed study results.

Molecular Targeted Therapy

  • Genomic Classes:
    • Inflammatory pathway activation.
    • Proliferative oncogene pathway activation (worse prognosis).
  • Molecular Markers:
    • K-ras mutations associated with poor survival.
  • Current Status:
    • Limited success with targeted therapies in trials.
    • Future Directions:
      • Mutation profiling to guide personalized therapy.
      • Clinical responses observed with specific inhibitors (e.g., EGFR, FGFR).

Palliation

Indications

  • Refractory malignant jaundice causing:
    • Cholangitis.
    • Intractable pruritus.
    • Need to optimize liver function before chemotherapy.

Principles

  • Effective Decompression:
    • Must drain >1/3 of functional liver mass.
  • Avoid Decompression of atrophic segments.
  • Recognize Jaundice from non-biliary causes (e.g., portal vein obstruction).

Methods

Operative Bypass

  • Procedures:
    • Hepaticojejunostomy for hilar tumors.
    • Choledochoenterostomy for distal tumors.
  • Considerations:
    • High durability and patency.
    • Higher morbidity and longer recovery.
    • Reserved for expected survival >6 months.

Nonoperative Drainage

  • Options:
    • Percutaneous biliary drainage.
    • Endoscopic stenting.
  • Stent Types:
    • Metallic stents: Longer patency (8–10 months).
    • Plastic stents: Shorter patency (4–5 months).
  • Adjunct Therapies:
    • Intraluminal brachytherapy: May prolong stent patency.

Surgical Techniques for Cholangiocarcinoma

Intrahepatic Cholangiocarcinoma

  • Standard Hepatic Resection:
    • Anatomic resection based on tumor location.
    • Ensure negative margins.

Distal Cholangiocarcinoma

  • Pancreaticoduodenectomy:
    • Removal of the distal bile duct, duodenum, pancreatic head, and gallbladder.

Hilar Cholangiocarcinoma

Preoperative Preparation

  • Imaging to assess resectability.
  • Possible Laparoscopy to detect metastases.

Surgical Steps

  1. Abdominal Exploration:
    • Through a bilateral subcostal or right transverse incision.
  2. Inspection:
    • Check for distant metastases and N2 nodal involvement.
  3. Vascular Control:
    • Maintain low central venous pressure.
    • Position patient in Trendelenburg to prevent air embolism.
  4. Bile Duct Division:
    • Divide supraduodenal bile duct.
    • Perform cholecystectomy.
  5. Dissection:
    • Free bile duct from portal vein and hepatic artery.
  6. Assess Need for Hepatectomy:
    • Based on biliary and vascular involvement.
  7. Partial Hepatectomy (if needed):
    • Mobilize liver by dividing peritoneal attachments.
    • Divide hepatic artery and portal vein to affected lobe.
    • Transect hepatic parenchyma.
  8. Reconstruction:
    • Roux-en-Y hepaticojejunostomy to restore biliary continuity.
    • Anastomose multiple ducts if necessary.

Central or Mesohepatectomy

  • Resection of Segments:
    • IVA, IVB, V, and VIII.
  • Indications:
    • Tumor location or insufficient future liver remnant.
  • Risks:
    • High morbidity (up to 55%).
    • Mortality around 6%.

Key Takeaways

  • Complete R0 resection is crucial for the best outcomes in cholangiocarcinoma.
  • Partial hepatectomy enhances the chance of negative margins, especially in hilar tumors.
  • Adjuvant therapies show promise but require more research for definitive guidelines.
  • Palliation focuses on relieving jaundice and maintaining quality of life.
  • Molecular profiling may guide future targeted therapies for personalized treatment.

Summary

Cholangiocarcinoma is a rare but serious cancer with varied presentations based on its location in the biliary system. Early diagnosis and achieving a complete surgical resection are critical for improving patient outcomes. Understanding the staging, surgical options, and potential adjuvant therapies is essential for managing this complex disease. Advances in molecular profiling hold promise for future targeted treatments.