Special Surgery 13. Primary and Metastatic Tumors of the Liver: Symptoms, Diagnosis, Treatment

I. Hepatocellular Carcinoma (HCC)

Definition and Etiology

• HCC: malignant tumor of hepatocytes
• Most common primary malignant liver tumor in adults
• Male predominance
• Usually develops in chronic liver disease / cirrhosis
• Main etiologies:

• Cirrhosis: alcohol, NASH/NAFLD, autoimmune liver disease, chronic viral hepatitis
• HBV and HCV infection; HBV can cause HCC without established cirrhosis
• Aflatoxin exposure: Aspergillus contamination
• Hemochromatosis and other metabolic liver diseases

Screening and Clinical Features

• At-risk cirrhotic patients: ultrasound every 6 months ± AFP according to local protocol
• Early stage: often asymptomatic
• Symptoms/signs:

• RUQ/epigastric pain or tenderness
• Weight loss, anorexia, fatigue
• Hepatomegaly or palpable mass
• Jaundice, ascites or worsening liver decompensation
• Rare: fever or tumor rupture → hemoperitoneum/shock

• Complications/spread:

• Portal/hepatic vein invasion
• Budd-Chiari-like syndrome: hepatic venous outflow obstruction → hepatomegaly + ascites
• Intrahepatic satellite nodules common
• Hematogenous metastasis in advanced disease: lung, bone, adrenal gland

Diagnosis

• Labs: liver enzymes can increase, especially AST/GOT
• Liver function assessment: bilirubin, albumin, INR, platelets, Child-Pugh/MELD, portal hypertension signs
• AFP: supportive tumor marker and useful for follow-up if elevated; not diagnostic alone
• Surveillance US detects suspicious nodules
• Confirmatory imaging: multiphasic contrast CT or MRI
• Typical HCC pattern in at-risk liver: arterial hyperenhancement + portal venous/delayed washout
• Staging imaging: liver tumor number/size, vascular invasion, lymph node/distant metastasis
• Biopsy: usually avoided if imaging is diagnostic because of bleeding/seeding risk
• Biopsy indicated if imaging is atypical, no high-risk background exists, or histology is needed before systemic therapy

Treatment Principles

• Decision by hepatobiliary MDT / liver tumor board
• Treatment depends on:

• Tumor size and number
• Vascular invasion and extrahepatic metastasis
• Liver function and portal hypertension
• Performance status
• Future liver remnant

Curative / Local HCC Treatment

1. Radiofrequency ablation / microwave ablation

• Early small HCC, best for tumors <= 2-3 cm
• Only if localization allows safe ablation margin
• Limitation: near major bile duct, bowel or large vessel

2. Liver transplantation

• Best if early HCC + impaired liver function or clinically significant portal hypertension
• Treats both tumor and cirrhotic liver
• Milan criteria:

• Single tumor <= 5 cm
• Or up to 3 tumors, each <= 3 cm
• No macrovascular invasion
• No distant metastasis

3. Surgical resection

• Curative option for localized HCC with sufficient liver reserve
• Best candidates: non-cirrhotic liver or well-compensated cirrhosis, no significant portal hypertension, preserved bilirubin, no nodal/distant metastasis
• Not limited strictly to <2-3 cm; larger solitary tumors may be resectable if anatomy and liver function allow
• Future liver remnant assessment: CT volumetry, 99mTc-mebrofenin SPECT/CT where available, ICG clearance in some centers
• If remnant too small: portal vein embolization, portal vein ligation, two-stage hepatectomy or selected ALPPS

Non-Curative / Advanced HCC Treatment

4. Transarterial chemoembolization (TACE)

• Intermediate stage, liver-confined disease, preserved liver function
• Catheter into hepatic arterial tumor supply → chemotherapy + embolization → ischemic necrosis

5. Systemic and palliative treatment

• Advanced stage: vascular invasion, distant metastasis or progression after local therapy
• Systemic therapy: immunotherapy-based combinations or tyrosine kinase inhibitors in fit patients with preserved liver function
• End-stage / poor liver function / poor performance status: best supportive care, pain/ascites/jaundice control

II. Intrahepatic Cholangiocarcinoma

Basic Concept and Risk Factors

• Primary adenocarcinoma from intrahepatic bile ducts
• Risk factors:

• Primary sclerosing cholangitis
• Choledochal cysts
• Liver flukes
• Chronic biliary inflammation
• Cirrhosis/chronic viral hepatitis can contribute

Symptoms, Diagnosis and Treatment

• Symptoms: fatigue, weight loss, RUQ discomfort
• Jaundice, pruritus, dark urine, pale stool if hilar/ductal obstruction occurs
• Diagnosis: CT/MRI shows mass; MRCP maps duct involvement/stricture
• Tumor markers: CA 19-9 and CEA supportive, not diagnostic alone
• Biopsy: needed if diagnosis unclear or before systemic therapy
• Only curative treatment: surgical resection with negative margins if resectable and patient fit
• Liver transplantation: only selected cases under strict protocols
• Unresectable/metastatic disease: systemic therapy, biliary drainage if obstructed, palliative care

III. Metastatic Liver Tumors

Definition and Primary Tumors

• Metastatic liver tumors: most common malignant tumors of the liver overall
• Common primary sites:

• Colorectal cancer: most common and most important surgically
• Pancreatic cancer
• Gastric cancer
• Lung cancer
• Breast cancer
• Neuroendocrine tumors

Clinical Features and Diagnosis

• Early stage: often asymptomatic
• Often found during staging or follow-up of primary tumor
• Symptoms/signs: RUQ pain/fullness, hepatomegaly, weight loss, anorexia, fatigue
• Late signs: jaundice, ascites, cachexia, liver failure
• Labs: liver enzymes may be normal or cholestatic if extensive disease
• Tumor markers according to primary tumor: CEA in colorectal cancer, CA 19-9 in pancreatic/GI tumors, others by context
• Contrast CT: often multiple hypodense liver lesions
• Liver MRI: best for small lesions and preoperative mapping
• PET-CT: useful in selected colorectal and neuroendocrine tumors / occult extrahepatic disease
• Biopsy: sometimes needed if primary tumor is unknown or imaging is atypical

Treatment

• Treatment depends on primary tumor biology, extrahepatic disease, resectability, liver remnant and patient fitness
• Colorectal liver metastases:

• R0 liver resection can be potentially curative and improves survival
• Resectable if all visible disease can be removed/ablated while preserving adequate inflow, outflow, biliary drainage and future liver remnant
• Neoadjuvant/conversion or adjuvant chemotherapy often used, e.g. FOLFOX-based regimens
• Ablation or embolization for selected unresectable/small lesions or combined treatment

• Neuroendocrine liver metastases:

• Resection/debulking or ablation in selected liver-dominant disease
• Systemic and receptor-targeted therapy depending on grade and primary site

• Breast, lung, stomach, pancreas, esophagus metastases:

• Usually systemic therapy according to primary tumor
• Liver surgery only in highly selected oligometastatic cases after MDT discussion

IV. Exam Summary

• Most common primary liver malignancy: HCC
• Most common malignant liver tumor overall: metastasis
• HCC surveillance in cirrhosis: US every 6 months ± AFP
• Typical HCC imaging: arterial enhancement + venous/delayed washout
• HCC curative options: ablation, resection, transplantation
• Transplant is best when early HCC coexists with poor liver function/portal hypertension and Milan criteria are met
• Resection needs adequate liver function and future liver remnant
• TACE: intermediate HCC; systemic/palliative therapy: advanced/end-stage HCC
• Colorectal liver metastasis is the key metastasis where liver resection can be curative