Definition
A.Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer in adults.
B.Other cancers that begin in the liver include intrahepatic cholangiocarcinoma (about 10%–20%) and less common tumors such as angiosarcomas, hemangiosarcomas, hepatoblastomas, and malignant epithelioid hemangioendotheliomas.
Incidence
A.Liver cancer occurs primarily in people ages 55 to 64, with a median age of 63 at diagnosis.
B.Liver and bile duct cancers are relatively rare when compared with other cancers.
C.In 2016, an estimated 39,230 cases were diagnosed in the United States, and about 27,170 people died of liver and intrahepatic cholangiocarcinoma.
D.The survival rate among individuals with liver cancer varies based on staging at the time of diagnosis.
E.Surveillance, epidemiology, and end results (SEER) data estimates that 43% of patients present with localized disease (confined to the primary site), 27% have disease that has spread to regional lymph nodes, and 18% present with distant metastases.
F.The 5-year relative survival rates for each are 30.9%, 10.9%, and 3.1%, respectively.
G.The incidence and mortality rates of HCC are on the rise in the United States.
Pathogenesis
A.There is a strong association with inflammation, necrosis, fibrosis, and cirrhosis in the development of HCC.
B.Some gene mutations have been identified as the cause of uncontrolled division of cells in the liver, leading to development of cancer.
C.HCC has several different subtypes, each with different growth patterns.
Predisposing Factors
A.Male sex.
B.Chronic hepatitis B and C virus infections.
C.Alcohol-related cirrhosis.
D.Nonalcoholic fatty liver disease (NAFLD).
E.Exposure to certain chemicals (e.g., nitrites, hydrocarbons, and polychlorinated biphenyls).
F.Dietary intake of aflatoxins (toxic metabolites produced by certain fungi in foods and feeds).
G.Metabolic disorders such as hemochromatosis, Wilson’s disease, and Alpha-1 antitrypsin deficiency.
Presence of hepatocellular adenoma (unclear risk of malignant transformation to HCC).
Subjective Data
A.The presentation of liver cancer is dependent upon the stage of disease.
B.Common complaints/symptoms.
1.Fatigue.
2.Abdominal pain/bloating.
3.Palpable mass in the right upper quadrant.
4.Signs and symptoms of liver disease: Ascites, jaundice, splenomegaly, portal hypertension.
5.Nausea.
6.Decreased appetite and early satiety.
7.Unexplained weight loss.
8.Fever.
Physical Examination
A.Check vital signs.
B.Head and neck.
1.Evaluate for scleral icterus.
2.Palpate the neck and supraclavicular area for adenopathy. Look for jugular venous distention.
C.Pulmonary system.
1.Observe the patient for signs of dyspnea, increased work of breathing, or retractions.
2.Auscultate all lung fields.
D.Cardiovascular system: Auscultate heart sounds.
E.Gastrointestinal system.
1.Perform a thorough abdominal examination.
2.Pay close attention to the right upper quadrant.
3.Assess for a fluid wave/evidence of ascites, hepatomegaly, an umbilical hernia, and caput medusae.
F.Musculoskeletal system.
1.Observe for signs of muscle wasting and cachexia.
2.Evaluate lower extremities for pitting edema.
G.Central nervous system: Assess cranial nerves II−XII.
H.Skin: Assess for jaundice, palmar erythema, and spider angiomata.
Diagnostic Tests
A.Laboratory evaluation should include complete blood count (CBC), comprehensive metabolic panel (CMP), prothrombin time/partial thromboplastin time/international normalized ratio (PT/PTT/INR), and prealbumin.
B.Tumor markers: Alpha fetoprotein (AFP) and cancer antigen 19–9 (CA 19–9).
C.CT of the chest, abdomen, and pelvis with contrast.
D.MRI of the abdomen and chest x-ray in patients with PO/IV contrast allergy.
E.EKG if considering surgery.
F.Liver tumor biopsy is generally not necessary when considering surgery in the setting of classic imaging findings, elevated tumor markers, and the presence of known risk factors. Patients with fatty liver disease may be referred for biopsy of their underlying (nontumoral) liver to evaluate for percent steatosis and fibrosis, as this impacts their candidacy for surgical resection.
G.Diagnosis.
1.Diagnosis typically requires a combination of laboratory data, imaging, and biopsy results.
2.Laboratory data.
a.Tumor markers are often elevated in patients with liver cancer and can be followed to assess response to therapy or monitored for disease progression.
b.AFP, while neither specific nor sensitive for HCC, is elevated in 50% to 90% of all patients with HCC.
c.CA 19–9 is a useful tumor marker and often elevated in cholangiocarcinoma.
3.Imaging.
a.Ultrasonography may be used as the initial screening technique in patients being monitored for chronic hepatitis; however, surgical resectability and treatment planning is always based on dedicated, multiphasic imaging of the chest, abdomen, and pelvis.
b.Triple phase CT assesses the blood flow to liver tissue during early arterial, late arterial, and portal venous phases.
c.CT imaging typically shows arterial phase enhancement in HCC due to increased vascular supply of the tumor from the hepatic artery.
d.Metastatic adenocarcinomas and cholangiocarcinomas typically enhance during the portal phase on CT.
4.Biopsy.
a.Tissue sampling/biopsy is recommended if the patient is not a candidate for surgery and targeted therapy or systemic chemotherapy is being considered.
b.Tissue for pathologic confirmation can be obtained through a percutaneous image-guided biopsy of the liver nodule/mass.
H.Staging.
1.The staging of HCC, like the majority of cancers, follows the American Joint Committee on Cancer (AJCC) tumor, node, metastasis (TNM) system.
2.Higher numbers indicate more advanced disease.
Differential Diagnosis
1.Cirrhosis.
2.Hepatocellular adenoma.
3.Cholangiocarcinoma.
Evaluation and Management Plan
A.General plan.
1.Patients with HCC may be offered surgery, targeted therapy/chemotherapy, radiation therapy, liver-directed therapy, or referral for transplantation depending upon multiple factors present at diagnosis including:
a.Geographic distribution of disease.
b.The presence of metastatic disease.
c.Age and comorbidities.
d.Cirrhosis.
e.Liver reserve.
2.Surgery.
3.Targeted therapy/chemotherapy.
4.Radiation therapy.
5.Liver-directed therapy includes percutaneous treatments.
a.Radiofrequency/laser/microwave ablation.
b.Cryotherapy.
c.Ethanol injection.
d.Transarterial chemoembolization (TACE).
e.Radioembolization.
6.Liver transplantation.
B.Acute care issues in hepatic cancer.
1.Liver cancer patients are often only admitted to the hospital after surgical resection or transplantation.
2.Patients either undergo a partial hepatectomy (removal of a portion of the right or left liver, which may or may not require resection of an entire segment) or a complete right or left hepatectomy. These surgeries can be performed laparoscopically, open, or via a minimally invasive approach. The gallbladder is sometimes removed at the time of liver resection.
3.Liver-directed therapies are generally performed in the outpatient setting but can occasionally require hospital admission.
Follow-Up
A.Postoperative liver surgery patients, without complications, will spend an average of 3 to 7 days in the hospital, depending upon the type of surgery performed (laparoscopic vs. open).
B.The primary focus in the postoperative inpatient setting is pain control, early ambulation, monitoring blood counts and liver function tests, wound/drain management, pulmonary toileting to avoid pneumonia, and prevention of blood clots.
C.Patients are evaluated by the inpatient dietician who stresses the importance of adequate protein and fluid intake in the perioperative period and after discharge.
Consultation/Referral
A.Most patients are treated by a multidisciplinary team including both surgical and medical oncologists who formulate a treatment plan based upon clinical staging.
B.Radiation oncologists may be consulted if radiation therapy is being considered.
C.Prior to surgery, patients are often referred to internal medicine to optimize and manage medical comorbidities in the perioperative period.
D.Patients with active hepatitis virus infections are managed by either infectious disease or hepatology specialists.
Special/Geriatric Considerations
A.Surgical resection is the only potentially curative treatment for most hepatic cancers.
B.Decisions to aggressively treat or not treat hepatic cancer in the geriatric population should not be based on age alone.
C.Factors such as life expectancy, quality of life, and patient functional status should be taken into consideration.
Bibliography
National Cancer Institute. (2016, September 12). Surveillance, epidemiology, and end results program. Retrieved from https://seer.cancer.gov/faststats/selections.php?series=cancer