Neoplasms/Malignancies

Hepatocellular Carcinoma

• HCC is a 3rd leading cancer cause worldwide.
• Incidence rates rising in Western countries, and 80% have cirrhosis.
• Risk factors: 
  • Male sex
  • Chronic Hep B/C infection.
  • Hemochromatosis
  • Alpha-1-antitrypsin deficiency 
  • (Any kind of cirrhosis)
• Screening / Surveillance
  • Cross-sectional imaging (Ultrasound is least epensive, CT - better resolution, detection of early stage).

• Screening guidelines for HCC: All patients with cirrhosis should be screened for HCC q6mo (every 6 months) with cross-sectional imaging. Serum AFP --> Not sufficient diagnostic accuracy alone for early detection. (Can do q12mo if hard to follow)

• Some patients do q12mo if hard to get back to clinic to do this screening.
• Diagnosis:
  • Lesions >2cm in diameter can be diagnosed with contrast enhanced CT/MRI/Angiography.
    • HCC derive their blood supply from neovascularization (from branches of hepatic artery).  This characteristic allows it to be identified by contrast-enhanced imaging (contrast CT or MRI). 
    • If positive for HCC --> can diagnose and treat as HCC. (Biopsy may not be required)
    • If negative --> does not rule out malignancy (can consider biopsy?)

    • Diagnosis of HCC: At least TWO imaging studies showing lesion with HCC features (Arterial hypervascularization with delayed venous contrast washout) OR If only one imaging study available, can diagnose if serum AFP level ≥ 400

  • Image guided biopsy: ONLY for patients in whom radiologic criteria are equivocal or inconsistent with HCC.
    • Negative biopsy result in cirrhosis does not confidently exlude HCC.
    • Tumor seeding from biopsy described, but rare.
  • 1 - 2 cm indeterminate lesions --> enhanced follow-up with more frequent imaging is required.
• Treatment:
  • Guided by Barcelona Classification for Liver Cancer (BCLC)  
    ---> see flow chart (look in  MKSAP16  PMID: 18477802)
    • Manage based on stage of liver disease (Childs-Pugh Classification - A/B/C/D)
    • Examples:
      • Early stage liver disease with small lesion + stable liver function: resect lesion. (enough liver preserved)
      • Multiple small lesions (3 of ≤ 3cm) and early stage disease --> liver transplant. 
      • Indeterminant stage or multinodular disease --> Transarterial hepatic artery chemoembolization (TACE)
      • Advanced stage, portal invasion --> Sorafenib
  • Transplantation is most effective for early disease.

Gallbaldder Cancer

• Most common biliary malignancy
• Risk Factors: >50yo, Female, Gall stones, obesity, gallbladder pollyps >1cm, chronic infection (salmonela typhii), porcelain gall bladder.

• To prevent gall bladder cancer, prophylactic cholecystectomy considered in: Gall bladder polyps >1cm Gall stones >3cm Porcelain gall bladder

• Uncommon, but fatal, diagnosed in advanced stage.
• Symptoms: Nonspecific: abdo discomfort, nausea, weight loss
• Labs: normal until obstructive jaundice develops
• Diagnosis:
  • Often diagnosed intra-op during cholecystectomy for gall bladder symptoms OR on abdo imaging.
  • U/S, CT, MRI can reveal abnormalities in gall bladder wall.
• Management:
  • Depends on stage.
  • Localized --> Open cholecystectomy.
  • Advanced Tumors --> Curative therapy not possible.
    • Palliative: operative diversion of bile flow, endoscopic stenting.
    • Chemotherapy/Radiation benefits not demonstrated.

Cholangiocarcinoma

• Cancer derived from biliary tree (not gall bladder or ampulla)
• Risk Factors: Primary sclerosing cholangitis, biliary atresia, chronic infection (liver flukes), biliary cists.
• Screening: No evidence for screening (imaging +/- tumor markers possible)
• Suspect in patients with PSC with signs of clinical decompensation.
• Management:
  • Classified:
    • Intrahepatic:
      • Often asymptomatic until advanced (RUQ discomfort, weight loss, fever, ALP can be up)
      • If advanced: poor prognosis, curative resection often not possible.  
    • Hilum (Klatskin tumor​) 
      • Jaundice (complete obstruction of biliary tree)
      • Suspect diagnosis: imaging shows bile duct dilatation + obstructing lesion
      • Diagnosis: Endoscopic cholangiography with brushings/biopsy
      • Management: Resection (if not invated intrahepatic ducts), poor survival
        • Liver transplant also done, but no data yet.
    • Extrahepatic (distal): 
      • ​Presentation / diagnosis is same as Hilum Tumor.
      • Management: resection (curative intent)
  • Chemo/Rads benefit unknown

Ampullary Adenocarcinoma

• RARE, often in hereditary polyposis syndromes (FAP).
• FAP patients should undergo regular endoscopy to screen.
• Presents: obstructive jaundice.  Dx: endoscopic biopsy and imaging with CT.
• Resectable, good prognosis. (Whipple procedure is recommended)

Biliary Cysts

• Diagnosis considered when dilatation of bile duct is found without evidence of obstructing lesion.
• Symptoms: chronic intermittent abdo pain, recurrent bouts of cholangitis / jaundice.
• Diagnosis:
  • Abdo CT / US can suggest cysts --> DO MRCP or ERCP
    • To diagnose use: MRCP, ERCP, or EUS (Endoscopic Ultrasound)
    • --> define cystic dilatation with no obstruction
• Management:
  • 20-fold increase risk of cholangiocarcinoma  --> should be resected.
    • Surgical resection of the entire cyst + hepaticojejunostomy formation indicated.
    • Reduces risk of malignancy and alleviates further cholangitis.