Gallbladder carcinoma and cholangiocarcinoma:�Investigations, staging and management

DR KGAKA

Gallbladder cancer

• Commonest Biliary tract cancers
• Incidence increases with age
• Female predilection
• Increasing in black females <45 years
• Location: Billiary (60%), Body (30%), Neck (20%)
• Type of differentiation: Billiary type, Intestinal type and Gastric-foveolar type
• Histopathological types: Papillary, mucinous, squamous, and adeno-squamous

Risk factors

• Cholelithiasis
• Porcelain gallbladder

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Other risk factors:

• anomalous pancreaticobiliary duct junction
• gallbladder polyps (>1 cm/>10mm)
• chronic typhoid infection
• primary sclerosing cholangitis
• inflammatory bowel disease
• Adenomyomatosis

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Diagnosis

• Usually diagnosed at an advanced stage –Asymptomatic

-Aggressive

• Clinical presentation mimics biliary colic and cholecystitits
• Diagnosis is usually incidental

Other possible clinical presentation:

• Suspicious mass detected on us
• Obstructive jaundice
• Chronic right upper quadrant pain

INVESTIGATIONS

1. Bloods

• LFTs
• CA 19-9 /CEA

2. Imaging

• Abdominal ultrasound: Screening tool
• CT scan of the abdomen: Identify tumour invasion outside of the gallbladder

-CT CHEST and Pelvis: Identify metastatic disease

• MRI-Liver: Helps define extent of invasion into the liver and differentiate benign from malignant disease. Diffusion weighted imaging is important
• PET CT scan: Has an advantage in resectable diseaseto pick up occult metastasis
• Endoscopic ultrasound: For diagnosis and staging

Staging

MANAGEMENT

CHOLANGIOCARCINOMA

Heterogenous group of tumours that arise from cholangiocytes that line the biliary tree

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Three divisions based on anatomic location:

• Hilar tumours: Between the main lobar extrahepatic

bile ducts and the cystic duct, the most common type

representing 50%-60% of cholangiocarcinoma)

• Distal bile duct tumours: Between the cystic duct

and the ampulla of Vater, representing 20%-30% of

cholangiocarcinoma)

• Intrahepatic tumours: Proximal to the extrahepatic

bile ducts, representing 10%-20% of cholangiocarcinoma)

• Second commonest primary liver malignancy
• Incidence increased by 22% between 1979 and 2004
• Mortality increased by 39%
• Mortality slightly greater in man vs women
• Intrahepatic cholangiocarcinoma <10% cases, peri-hilar CCA>50%and distal CCA <40% cases

Risk factors

• Sporadic
• Incidence vary among populations of different geographic regions
• Thailand incidence 113/100000 –hepatobiliary flukes
• Bile duct cystic disorders among Asians
• Sclerosing cholangitis
• Cirrhosis and hepatitis B, C
• Hepatolithiasis
• Biliary-enteric drainage
• Diabetes,obesity,alcohol and smoking-further evidence required

Histological types

Most cholangiocarcinomas are adenocarcinomas

• Nodular
• Sclerosing
• Papillary

Papillary tumors have the highest cure and resectability rates and is the least common type.

Intrahepatic cholangiocarcinoma

• Cholangiocarcinomas arising from the intrahepatic biliary tract
• Usual presentation: Intrahepatic mass lesion
• Intrahepatic mass lesion- Rule out other sources of malignancy
• If liver biopsy shows adenocarcinoma, rule out other primary tumours
• Adenorcinoma –commonest metastatic lesion of the liver

Macroscopic growth patterns:

• Mass forming: Commonest
• Peri-ductal: Infiltrating
• Intra-ductal
• Superficial spreading
• Undefined

Extrahepatic cholangiocarcinoma

• Diagnosis of this type of cholangiocarcinoma is difficult
• Currently there is no definitive high-yield test to confirm a histologic diagnosis of cholangiocarcinoma.

INVESTIGATIONS

1 Blood:

• LFT
• CA 19-9: 90% Sensitivity and 98% with levels of 100 U/ml. Levels >1000 U/ml are associated with occult metastasis
• CEA: Has prognostic value. Raised in locally advanced disease.
• Tumour mutation Testing: Genetic DNA testing, BRAFV600E, NTRK gene fusion (For targeted therapy)

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2. Ultrasound

• Often first to be ordered in the clinical setting in patients with RUQ pain or jaundice
• Used to visualize intrahepatic or extrahepatic biliary dilation.
• Contrast enhanced u/s: Shows gross lesions or solid mass with biliary dilatation.

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3. CT scan of the abdomen:

• Should be obtained before endoscopic or percutaneous intervention in the bile ducts.
• Characteristics of the primary tumour, relationship with adjacent structures, vascular invasion and metastasis. Poor sensitivity for nodal invasion compared to MRI

INVESTIGATIONS

4. MRI: Highly accurate, incorporates DWI and MRCP which is beneficial for pCCA staging. Unable to assess vascular invasion

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5. ERCP and percutaneous transhepatic cholangiogram

• Evaluate the etiology and level of duct obstruction
• Brushings for cytology obtained during these procedures have a low sensitivity (approximately 15%-25%)
• Additional diagnostic measures including fluorescence in situ hybridization (FISH, sensitivity as high as 69%)
• Spyglass (sensitivity as high as 68%-90%) have been shown to increase the diagnostic yield.

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6.EUS: Sensitivity up to 100% for dCCA and 83% for pCCA. Best for lymph node staging and bile duct brushing

STAGING

Staging is performed preoperatively with cross-sectional imaging:

• CT
• MRI
• MRCP
• PET CT scan-Recommended by NCCN guidelines

This can help identify occult metastases, multifocal tumors, or extension to blood vessels or second-order biliary radicals

Staging: Hilar cholangiocarcinoma

Blumgart staging system : Used pre-operatively and correlates with :

• Resectability, involvement of the portal system and associated liver atrophy
• Presence of nodal or distant metastatic disease

The Bismuth-Corlette classification uses pre-operative imaging :

• Describes longitudinal tumor extension along the biliary ducts -Does not consider radial growth.

AJCC staging is mainly used after surgical resection

Bismuth-Corlette classification

Staging laparoscopy

Staging laparoscopy is performed selectively or routinely to identify:

• Tumour resectability
• To exclude metastatic disease not detected on cross-sectional imaging

MANAGEMENT

• Principles of liver resection

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Assessment of resectability

Management

Chemotherapy principle and drugs

• Primary treatment for un-resectable and metastatic disease
• Preferred regimen: Gemcitabine plus cisplatin
• Subsequent line therapy for cancers if progression:
• Preferred regimen: FOLFOX
• Other recommendation: FOLFIRI, Regorafenib

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PALLIATION

Obstructive jaundice

• Intra-operative findings of un-resectability or positive distal CBD margin
• Biliary-enteric bypass
• Pre-operative:
• PTBD or ERCP

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Pain:

• Narcotics

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Duodenal obstruction:

• Duodenal stenting