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Hepatocellular Carcinoma (HCC) and Liver Metastases

Hepatocellular carcinoma (HCC) typically arises in a chronically diseased or cirrhotic liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy and is the most common primary liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy cancer. Diagnosis may include ultrasound, CT, MRI, biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma (if inconclusive imaging), and/or biomarkers. Treatment options include resection and chemo-/radiotherapy, and liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy transplantation in select cases.  Liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy metastases are much more common than primary liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy cancers and usually originate from colorectal, lung, breast, and pancreatic primary sites. Metastases are most commonly diagnosed by CT or PET PET An imaging technique that combines a positron-emission tomography (PET) scanner and a ct X ray scanner. This establishes a precise anatomic localization in the same session. Nuclear Imaging scans. Management depends on the type and stage of primary cancer.

Last updated: Sep 10, 2021

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Epidemiology and Etiology

Epidemiology

  • Hepatocellular carcinoma (HCC) accounts for 80% of primary liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy cancers in adults.
  • Mortality-to-incidence ratio (MIR): 0.95 (2nd-worst survival rate after pancreatic cancer) 
  • Worldwide:
    • 5.4% of all cancers
    • 4th most common cause of all cancer deaths
    • 85% of cases occur in Asia ASIA Spinal Cord Injuries and Sub-Saharan Africa:
      • Associated with a high rate of maternal-fetal transmission of hepatitis B Hepatitis B Hepatitis B virus (HBV) is a partially double-stranded DNA virus, which belongs to the Orthohepadnavirus genus and the Hepadnaviridae family. Most individuals with acute HBV infection are asymptomatic or have mild, self-limiting symptoms. Chronic infection can be asymptomatic or create hepatic inflammation, leading to liver cirrhosis and hepatocellular carcinoma (HCC). Hepatitis B Virus virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology ( HBV HBV Hepatitis B virus (HBV) is a partially double-stranded DNA virus, which belongs to the Orthohepadnavirus genus and the Hepadnaviridae family. Hepatitis B virus is transmitted by exposure to infectious blood or body fluids. Examples of types of exposure include sexual intercourse, IV drug use, and childbirth. Hepatitis B Virus)
      • Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency rates have decreased in areas with increased rates of HBV HBV Hepatitis B virus (HBV) is a partially double-stranded DNA virus, which belongs to the Orthohepadnavirus genus and the Hepadnaviridae family. Hepatitis B virus is transmitted by exposure to infectious blood or body fluids. Examples of types of exposure include sexual intercourse, IV drug use, and childbirth. Hepatitis B Virus vaccination Vaccination Vaccination is the administration of a substance to induce the immune system to develop protection against a disease. Unlike passive immunization, which involves the administration of pre-performed antibodies, active immunization constitutes the administration of a vaccine to stimulate the body to produce its own antibodies. Vaccination.
      • Age at diagnosis: 20–40 years 
      • Male-to-female ratio: 8:1
  • United States:
    • < 2.5% of all cancers
    • 5th most common cause of all cancer deaths
    • Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency is increasing (mostly due to non-alcoholic fatty liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy disease (NAFLD)).
    • Ethnic variations: Asians/Pacific Islanders > Blacks > Native Americans/Alaska Natives > Whites
    • Median Median After arranging the data from loWest to highest, the median is the middle value, separating the lower half from the upper half of the data set. Measures of Central Tendency and Dispersion age at diagnosis: 65 years
    • Male-to-female ratio: 3:1

Risk factors

Cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis:

One-third of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis will develop HCC during their lifetime, including those caused by:

  • Chronic HBV HBV Hepatitis B virus (HBV) is a partially double-stranded DNA virus, which belongs to the Orthohepadnavirus genus and the Hepadnaviridae family. Hepatitis B virus is transmitted by exposure to infectious blood or body fluids. Examples of types of exposure include sexual intercourse, IV drug use, and childbirth. Hepatitis B Virus
  • Chronic hepatitis C Hepatitis C Hepatitis C is an infection of the liver caused by the hepatitis C virus (HCV). The infection can be transmitted through infectious blood or body fluids and may be transmitted during childbirth or through IV drug use or sexual intercourse. Hepatitis C virus can cause both acute and chronic hepatitis, ranging from a mild to a serious, lifelong illness including liver cirrhosis and hepatocellular carcinoma (HCC). Hepatitis C Virus virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology ( HCV HCV Hepatitis C is an infection of the liver caused by the hepatitis C virus (HCV). Hepatitis C virus is an RNA virus and a member of the genus Hepacivirus and the family Flaviviridae. The infection can be transmitted through infectious blood or body fluids and may be transmitted during childbirth or through IV drug use or sexual intercourse. Hepatitis C Virus) infection
  • NAFLD (increased risk even without cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis)
  • Alcoholic Alcoholic Persons who have a history of physical or psychological dependence on ethanol. Mallory-Weiss Syndrome (Mallory-Weiss Tear) liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy disease
  • Hemochromatosis Hemochromatosis A disorder of iron metabolism characterized by a triad of hemosiderosis; liver cirrhosis; and diabetes mellitus. It is caused by massive iron deposits in parenchymal cells that may develop after a prolonged increase of iron absorption. Hereditary Hemochromatosis
  • α-1 antitrypsin (AAT) deficiency

Other:

  • Aflatoxin B1:
    • Toxin from Aspergillus Aspergillus A genus of mitosporic fungi containing about 100 species and eleven different teleomorphs in the family trichocomaceae. Echinocandins flavus and A. parasiticus fungi Fungi A kingdom of eukaryotic, heterotrophic organisms that live parasitically as saprobes, including mushrooms; yeasts; smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi, commonly known as molds, refer to those that grow as multicellular colonies. Mycology
    • Contaminates stored food products (e.g., peanuts, corn) 
    • Acts synergistically with HBV HBV Hepatitis B virus (HBV) is a partially double-stranded DNA virus, which belongs to the Orthohepadnavirus genus and the Hepadnaviridae family. Hepatitis B virus is transmitted by exposure to infectious blood or body fluids. Examples of types of exposure include sexual intercourse, IV drug use, and childbirth. Hepatitis B Virus infection and alcohol ingestion
  • Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases
  • Alcohol
  • Obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity
  • Wilson disease Wilson disease Wilson disease (hepatolenticular degeneration) is an autosomal recessive disorder caused by various mutations in the ATP7B gene, which regulates copper transport within hepatocytes. Dysfunction of this transport mechanism leads to abnormal copper accumulations in the liver, brain, eyes, and other organs, with consequent major and variably expressed hepatic, neurologic, and psychiatric disturbances. Wilson’s Disease
  • Chronic biliary disease
  • Autoimmune hepatitis Autoimmune hepatitis Autoimmune hepatitis (AIH) is a rare form of chronic liver disease in which the immune system attacks the liver causing inflammation. It predominantly affects women. Clinical presentation ranges from asymptomatic cases to patients that present with symptoms of acute liver failure (jaundice, right upper quadrant pain). Autoimmune Hepatitis

Pathogenesis and Pathology

Pathogenesis

  • HCC arising in chronic liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy disease with cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis (80% of cases):
    • Chronic injury → inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation → hepatocyte regeneration Regeneration The physiological renewal, repair, or replacement of tissue. Wound Healing → driver mutations of HCC 
    • Driver mutations and frequencies: 
      • β-catenin gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics (40%)
      • TERT gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics promoter → upregulates telomerase Telomerase An essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic chromosomes. DNA Replication activity (50-60%) 
      • TP53: inactivation mutations (60%)
  • HCC arising in noncirrhotic livers with preexisting chronic liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy disease:
    • Aflatoxin B1 → converted to toxic epoxide → damage to DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure (including p53)
    • Hepatocellular adenoma Hepatocellular adenoma A benign epithelial tumor of the liver. Benign Liver Tumors with β-catenin–activating mutations
    • Fibrolamellar type of HCC: fusion gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics forms → aberrant activity of protein kinase Protein kinase A family of enzymes that catalyze the conversion of ATP and a protein to adp and a phosphoprotein. Interferons A (PKA)→ abnormal activity of cAMP cAMP An adenine nucleotide containing one phosphate group which is esterified to both the 3′- and 5′-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and acth. Phosphodiesterase Inhibitors

Precursor (premalignant) lesions

Hepatocytes Hepatocytes The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. Liver: Anatomy show “large-cell change” and “small-cell change” with abnormal architecture (thick trabeculae) microscopically.

  • Large-cell change: enlarged hepatocytes Hepatocytes The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. Liver: Anatomy with large, multinucleated and pleomorphic Pleomorphic Bacteroides nuclei
  • Small-cell change: hepatocytes Hepatocytes The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. Liver: Anatomy with a high nuclear-to-cytoplasmic ratio, but mild nuclear change
  • Dysplastic nodules: often associated with small-cell change

Hepatocellular carcinoma (HCC)

Gross appearance:

  • Usually in a cirrhotic liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy
  • Single or multiple masses (discrete or infiltrative)
  • Extensive intrahepatic metastases are common.
  • Color:
  • Portal vein Portal vein A short thick vein formed by union of the superior mesenteric vein and the splenic vein. Liver: Anatomy invasion: common with extension Extension Examination of the Upper Limbs to the inferior vena cava Inferior vena cava The venous trunk which receives blood from the lower extremities and from the pelvic and abdominal organs. Mediastinum and Great Vessels: Anatomy and right side of the heart 
  • Vena cava invasion: HCC and renal cell carcinoma Renal cell carcinoma Renal cell carcinoma (RCC) is a tumor that arises from the lining of the renal tubular system within the renal cortex. Renal cell carcinoma is responsible for 80%-85% of all primary renal neoplasms. Most RCCs arise sporadically, but smoking, hypertension, and obesity are linked to its development. Renal Cell Carcinoma are the 2 carcinomas with a propensity to invade the vena cava as a growing thrombus.

Microscopic appearance:

  • Well-differentiated tumors:
    • Resemble normal hepatocytes Hepatocytes The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. Liver: Anatomy
    • Thickened trabeculae
    • Dilated and irregular canaliculi
    • Pseudoglandular spaces
  • Poorly-differentiated tumors:

Clinical Presentation

Four possible clinical presentations for HCC:

  1. Asymptomatic: HCC liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast is found incidentally on imaging.
  2. Cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis 1st:
    • Symptoms and signs of cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis appear 1st
    • The discovery of HCC follows
  3. Decompensated cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis in the presence of known cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis:
    • Variceal bleeding
    • Ascites Ascites Ascites is the pathologic accumulation of fluid within the peritoneal cavity that occurs due to an osmotic and/or hydrostatic pressure imbalance secondary to portal hypertension (cirrhosis, heart failure) or non-portal hypertension (hypoalbuminemia, malignancy, infection). Ascites
    • Extension Extension Examination of the Upper Limbs of HCC into the hepatic or portal veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins: Histology
  4. HCC 1st:
    • Symptoms and signs of HCC appear 1st
    • Abdominal pain Abdominal Pain Acute Abdomen/RUQ discomfort
    • Malaise Malaise Tick-borne Encephalitis Virus, fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia, weight loss Weight loss Decrease in existing body weight. Bariatric Surgery
    • Hepatomegaly, splenomegaly Splenomegaly Splenomegaly is pathologic enlargement of the spleen that is attributable to numerous causes, including infections, hemoglobinopathies, infiltrative processes, and outflow obstruction of the portal vein. Splenomegaly, palpable mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast
    • Tumor Tumor Inflammation rupture with intraperitoneal Intraperitoneal Peritoneum: Anatomy hemorrhage (life-threatening event)
    • Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever due to tumor Tumor Inflammation necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage
    • Obstructive jaundice Jaundice Jaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice
    • Extrahepatic metastases (10%–15% of cases): lung > regional lymph nodes Lymph Nodes They are oval or bean shaped bodies (1 – 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy > peritoneum Peritoneum The peritoneum is a serous membrane lining the abdominopelvic cavity. This lining is formed by connective tissue and originates from the mesoderm. The membrane lines both the abdominal walls (as parietal peritoneum) and all of the visceral organs (as visceral peritoneum). Peritoneum: Anatomy > bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types > adrenal gland

Diagnosis

Ultrasound

Surveillance Surveillance Developmental Milestones and Normal Growth screening Screening Preoperative Care by ultrasound every 6 months is recommended for patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship in the following high-risk groups:

  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis (annual incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency of HCC > 1.5%):
    • Least severe and moderately severe (Child-Pugh classification A and B)
    • Most severe (Child-Pugh classification C) if awaiting liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy transplantation
  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship without cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis (annual incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency of HCC > 0.2%) with HBV HBV Hepatitis B virus (HBV) is a partially double-stranded DNA virus, which belongs to the Orthohepadnavirus genus and the Hepadnaviridae family. Hepatitis B virus is transmitted by exposure to infectious blood or body fluids. Examples of types of exposure include sexual intercourse, IV drug use, and childbirth. Hepatitis B Virus infection, occurring in any of the following settings or patient types:
    • Active hepatitis (elevated serum alanine Alanine A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system. Synthesis of Nonessential Amino Acids aminotransferase and/or high viral load Viral load The quantity of measurable virus in a body fluid. Change in viral load, measured in plasma, is sometimes used as a surrogate marker in disease progression. HIV Infection and AIDS)
    • Family history Family History Adult Health Maintenance of HCC
    • Africans and African-Americans
    • Asian men > 40 years of age
    • Asian women > 50 years of age
  • Chronic HCV HCV Hepatitis C is an infection of the liver caused by the hepatitis C virus (HCV). Hepatitis C virus is an RNA virus and a member of the genus Hepacivirus and the family Flaviviridae. The infection can be transmitted through infectious blood or body fluids and may be transmitted during childbirth or through IV drug use or sexual intercourse. Hepatitis C Virus and advanced liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans (not included for surveillance Surveillance Developmental Milestones and Normal Growth screening Screening Preoperative Care by all experts)
  • Ultrasound findings:
Hcc on ultrasound

Hepatocellular carcinoma (HCC) on ultrasound: ultrasound images of HCC in the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy of a 31-year-old man with cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis
B1: conventional ultrasound showing the mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast as a poorly defined, hypoechoic Hypoechoic A structure that produces a low-amplitude echo (darker grays) Ultrasound (Sonography) nodule Nodule Chalazion
B2, B3, B4: time-sequenced contrast-enhanced ultrasound (CEUS) images after injection of a microbubble contrast agent
B2: typical hypervascularity (enhancement) of HCC during the arterial phase at 95 sec after injection of the contrast agent
B3, B4: mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast becoming hypoechoic Hypoechoic A structure that produces a low-amplitude echo (darker grays) Ultrasound (Sonography) in the portal and late phases
B4: late-phase image showing mild washout of contrast medium at 179 sec, which helps differentiate HCC from cholangiocarcinoma Cholangiocarcinoma A malignant tumor arising from the epithelium of the bile ducts. Rare Malignant Liver Tumors or metastatic tumor Tumor Inflammation (more rapid washout times)

Image: “Hepatocellular carcinoma (HCC) with moderate differentiation in a 31-year-old man with cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis” by Li R, Yuan MX, Ma KS KS Kallmann syndrome (KS), also called olfacto-genital syndrome, is a genetic condition that causes hypogonadotropic hypogonadism due to decreased secretion of gonadotropin-releasing hormone (GNRH) by the hypothalamus. The lack of sex hormones results in impaired pubertal development. Kallmann Syndrome, Li XW, Tang CL, Zhang XH, Guo DY, Yan XC. License: CC BY 4.0

CT or MRI

If ultrasound shows a lesion > 1 cm, dynamic contrast imaging by CT or MRI is performed.

  • Abdominal triphasic CT: confirmatory test showing enhancement in the arterial phase and washout during the portal venous phase with possible local invasion
  • MRI (with contrast): hypodense, irregular lesions

Biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma

If imaging results are unequivocal, a biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma is not always needed. 

  • Perform if the lesion is > 1 cm and tissue confirmation would change management.
  • Risk of bleeding and tumor Tumor Inflammation spread (< 3% cases)

Serum markers

  • Not used as stand-alone tests
  • Serum alpha-fetoprotein (AFP): insufficient sensitivity and specificity Sensitivity and Specificity Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. Epidemiological Values of Diagnostic Tests
  • Plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products microRNA (miRNA): shows promise as diagnostic and prognostic tools, but not sufficiently studied yet

Management and Complications

Nonsurgical options

  • Radiofrequency ablation (RFA), microwave ablation, and cryoablation Cryoablation Fibroadenoma
  • Irreversible electroporation (electropermeabilization with high-current electrical pulses)
  • Transarterial chemoembolization (TACE) and bland embolization Embolization A method of hemostasis utilizing various agents such as gelfoam, silastic, metal, glass, or plastic pellets, autologous clot, fat, and muscle as emboli. It has been used in the treatment of spinal cord and intracranial arteriovenous malformations, renal arteriovenous fistulas, gastrointestinal bleeding, epistaxis, hypersplenism, certain highly vascular tumors, traumatic rupture of blood vessels, and control of operative hemorrhage. Gastrointestinal Bleeding
  • Transarterial radioembolization (TARE)
  • Percutaneous ethanol Ethanol A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. Ethanol Metabolism or acetic acid ablation
  • Stereotactic radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma therapy
  • Systemic chemotherapy Chemotherapy Osteosarcoma and radiotherapy
  • Immunotherapy (studies in progress)

Surgical tumor Tumor Inflammation resection

  • Only 10% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship have resectable tumors. 
  • Eligibility limited by:
    • Cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis due to decreased hepatic reserve (limits resection)
    • Extensive tumor Tumor Inflammation present within the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy

Liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy transplantation

  • Absolute contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation: extrahepatic disease, vascular invasion
  • Bridging methods (usually with RFA or TACE) to prevent tumor Tumor Inflammation progression while awaiting a donor, and to downsize the tumor Tumor Inflammation to fit into eligibility criteria 

Complications

  • Paraneoplastic syndromes Paraneoplastic syndromes Paraneoplastic syndromes are a heterogeneous group of disorders caused by an abnormal immune response to a neoplasm. The substances produced are not due to the direct effect of the tumor, such as metastasis, mass effect, or invasion. Antibodies, hormones, cytokines, and other substances are generated and affect multiple organ systems. Paraneoplastic Syndromes (20%):
    • Hypoglycemia Hypoglycemia Hypoglycemia is an emergency condition defined as a serum glucose level ≤ 70 mg/dL (≤ 3.9 mmol/L) in diabetic patients. In nondiabetic patients, there is no specific or defined limit for normal serum glucose levels, and hypoglycemia is defined mainly by its clinical features. Hypoglycemia: due to high metabolism of the tumor Tumor Inflammation, or tumor Tumor Inflammation secretion Secretion Coagulation Studies of insulin-like growth factor-2
    • Hypercalcemia Hypercalcemia Hypercalcemia (serum calcium > 10.5 mg/dL) can result from various conditions, the majority of which are due to hyperparathyroidism and malignancy. Other causes include disorders leading to vitamin D elevation, granulomatous diseases, and the use of certain pharmacological agents. Symptoms vary depending on calcium levels and the onset of hypercalcemia. Hypercalcemia: due to osteolytic lesions, or tumor Tumor Inflammation secretion Secretion Coagulation Studies of parathyroid Parathyroid The parathyroid glands are 2 pairs of small endocrine glands found in close proximity to the thyroid gland. The superior parathyroid glands are lodged within the parenchyma of the upper poles of the right and left thyroid lobes; the inferior parathyroid glands are close to the inferior tips or poles of the lobes. Parathyroid Glands: Anatomy hormone-related protein
    • Erythrocytosis: likely due to tumor Tumor Inflammation secretion Secretion Coagulation Studies of erythropoietin Erythropoietin Glycoprotein hormone, secreted chiefly by the kidney in the adult and the liver in the fetus, that acts on erythroid stem cells of the bone marrow to stimulate proliferation and differentiation. Erythrocytes: Histology 
    • Diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea (may be intractable): likely due to secretion Secretion Coagulation Studies of peptides causing intestinal secretion Secretion Coagulation Studies (e.g., vasoactive intestinal polypeptide Vasoactive intestinal polypeptide A highly basic, 28 amino acid neuropeptide released from intestinal mucosa. It has a wide range of biological actions affecting the cardiovascular, gastrointestinal, and respiratory systems and is neuroprotective. It binds special receptors (receptors, vasoactive intestinal peptide). VIPoma, gastrin Gastrin A family of gastrointestinal peptide hormones that excite the secretion of gastric juice. They may also occur in the central nervous system where they are presumed to be neurotransmitters. Gastrointestinal Secretions, prostaglandin-like eicosanoids Eicosanoids Eicosanoids are cell-signaling molecules produced from arachidonic acid. With the action of phospholipase A2, arachidonic acid is released from the plasma membrane. The different families of eicosanoids, which are prostaglandins (PGs), thromboxanes (TXA2s), prostacyclin (PGI2), lipoxins (LXs), and leukotrienes (LTs), emerge from a series of reactions catalyzed by different enzymes. Eicosanoids)
    • Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions lesions (rare): dermatomyositis Dermatomyositis A subacute or chronic inflammatory disease of muscle and skin, marked by proximal muscle weakness and a characteristic skin rash. The illness occurs with approximately equal frequency in children and adults. The skin lesions usually take the form of a purplish rash (or less often an exfoliative dermatitis) involving the nose, cheeks, forehead, upper trunk, and arms. The disease is associated with a complement mediated intramuscular microangiopathy, leading to loss of capillaries, muscle ischemia, muscle-fiber necrosis, and perifascicular atrophy. The childhood form of this disease tends to evolve into a systemic vasculitis. Dermatomyositis may occur in association with malignant neoplasms. Paraneoplastic Syndromes, pemphigus foliaceus, Leser-Trélat sign Leser-Trélat Sign Paraneoplastic Syndromes (sudden appearance of multiple seborrheic keratoses, skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions tags, and acanthosis nigricans Acanthosis nigricans A circumscribed melanosis consisting of a brown-pigmented, velvety verrucosity or fine papillomatosis appearing in the axillae and other body folds. It occurs in association with endocrine disorders, underlying malignancy, administration of certain drugs, or as in inherited disorder. Diabetes Mellitus)
  • Tumor Tumor Inflammation rupture with intraperitoneal Intraperitoneal Peritoneum: Anatomy hemorrhage (an emergent, life-threatening event)
  • Budd-Chiari syndrome Budd-Chiari syndrome Budd-Chiari syndrome is a condition resulting from the interruption of the normal outflow of blood from the liver. The primary type arises from a venous process (affecting the hepatic veins or inferior vena cava) such as thrombosis, but can also be from a lesion compressing or invading the veins (secondary type). The patient typically presents with hepatomegaly, ascites, and abdominal discomfort. Budd-Chiari Syndrome: tumor Tumor Inflammation compresses and obstructs the hepatic veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins: Histology

Prognosis and Prevention

Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas

  • 4 important determinants of survival:
    • The severity of the underlying liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy disease
    • Tumor Tumor Inflammation size
    • Extension Extension Examination of the Upper Limbs of the tumor Tumor Inflammation into adjacent structures
    • Presence or absence of metastases
  • Treatment must be individualized: Some patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with poor prognostic determinants do well with aggressive therapy (including liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy transplantation).
  • Survival: 
    • Due to late-stage presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor, the 5-year survival rate is poor (10%–12%).
    • The 2nd-worst survival rate after pancreatic cancer
    • 5-year survival by determinants:
      • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy transplantation: 70%–75%
      • Tumor Tumor Inflammation limited to the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy: 30%
      • Regional extension Extension Examination of the Upper Limbs of tumor Tumor Inflammation: 12%
      • Distant metastases: 2.5%
    • Median Median After arranging the data from loWest to highest, the median is the middle value, separating the lower half from the upper half of the data set. Measures of Central Tendency and Dispersion survival:
      • < 3 months in parts of Africa
      • > 3 years in Taiwan and Japan

Prevention

  • HBV HBV Hepatitis B virus (HBV) is a partially double-stranded DNA virus, which belongs to the Orthohepadnavirus genus and the Hepadnaviridae family. Hepatitis B virus is transmitted by exposure to infectious blood or body fluids. Examples of types of exposure include sexual intercourse, IV drug use, and childbirth. Hepatitis B Virus vaccination Vaccination Vaccination is the administration of a substance to induce the immune system to develop protection against a disease. Unlike passive immunization, which involves the administration of pre-performed antibodies, active immunization constitutes the administration of a vaccine to stimulate the body to produce its own antibodies. Vaccination
  • Treatment for viral hepatitis: 
    • HBV HBV Hepatitis B virus (HBV) is a partially double-stranded DNA virus, which belongs to the Orthohepadnavirus genus and the Hepadnaviridae family. Hepatitis B virus is transmitted by exposure to infectious blood or body fluids. Examples of types of exposure include sexual intercourse, IV drug use, and childbirth. Hepatitis B Virus: Relative risk Relative risk Relative risk (RR) is the risk of a disease or condition occurring in a group or population with a particular exposure relative to a control (unexposed) group. Measures of Risk is reduced by 50%–60% with interferon or nucleoside derivatives.
    • HCV HCV Hepatitis C is an infection of the liver caused by the hepatitis C virus (HCV). Hepatitis C virus is an RNA virus and a member of the genus Hepacivirus and the family Flaviviridae. The infection can be transmitted through infectious blood or body fluids and may be transmitted during childbirth or through IV drug use or sexual intercourse. Hepatitis C Virus: Antiviral Antiviral Antivirals for Hepatitis B therapy decreases, but does not eliminate, risk.
  • Medications:
    • Statins Statins Statins are competitive inhibitors of HMG-CoA reductase in the liver. HMG-CoA reductase is the rate-limiting step in cholesterol synthesis. Inhibition results in lowered intrahepatocytic cholesterol formation, resulting in up-regulation of LDL receptors and, ultimately, lowering levels of serum LDL and triglycerides. Statins (HMGR inhibitors):
      • Most profound effect in East Asian men with chronic hepatitis
      • Statins Statins Statins are competitive inhibitors of HMG-CoA reductase in the liver. HMG-CoA reductase is the rate-limiting step in cholesterol synthesis. Inhibition results in lowered intrahepatocytic cholesterol formation, resulting in up-regulation of LDL receptors and, ultimately, lowering levels of serum LDL and triglycerides. Statins may indirectly reduce HCC by slowing the progression of cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis.
    • Aspirin Aspirin The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. Nonsteroidal Antiinflammatory Drugs (NSAIDs): Long-term, regular Regular Insulin use lowers the risk of HCC.
    • Metformin Metformin A biguanide hypoglycemic agent used in the treatment of non-insulin-dependent diabetes mellitus not responding to dietary modification. Metformin improves glycemic control by improving insulin sensitivity and decreasing intestinal absorption of glucose. Non-insulinotropic Diabetes Drugs: associated with lower overall cancer risk, including HCC
  • Lifestyle factors:
    • Physical activity: associated with lower risk of liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy cancer compared with a sedentary lifestyle
    • Diet consumption: White meat, fish FISH A type of in situ hybridization in which target sequences are stained with fluorescent dye so their location and size can be determined using fluorescence microscopy. This staining is sufficiently distinct that the hybridization signal can be seen both in metaphase spreads and in interphase nuclei. Chromosome Testing, omega-3 fatty acids Omega-3 fatty acids A group of unsaturated fatty acids occurring mainly in fish oils, with three double bonds at particular positions in the hydrocarbon chain. Lipid Control Drugs, vegetables, and vitamin E Vitamin E A generic descriptor for all tocopherols and tocotrienols that exhibit alpha-tocopherol activity. By virtue of the phenolic hydrogen on the 2h-1-benzopyran-6-ol nucleus, these compounds exhibit varying degree of antioxidant activity, depending on the site and number of methyl groups and the type of isoprenoids. Fat-soluble Vitamins and their Deficiencies are protective.
    • Coffee Coffee A beverage made from ground coffee beans (seeds) infused in hot water. It generally contains caffeine and theophylline unless it is decaffeinated. Constipation consumption: protective factor against HCC (contains abundant amounts of antioxidants Antioxidants Naturally occurring or synthetic substances that inhibit or retard oxidation reactions. They counteract the damaging effects of oxidation in animal tissues. Cell Injury and Death)

Liver metastases

  • 30x more common than primary liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy cancers
  • 40%–50% of people with death from malignancy Malignancy Hemothorax have a metastatic tumor Tumor Inflammation in the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy.
  • The most common types of cancer to spread to the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy are:
    • Colorectal
    • Lung
    • Breast
    • Pancreatic
    • Stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy
    • Melanoma Melanoma Melanoma is a malignant tumor arising from melanocytes, the melanin-producing cells of the epidermis. These tumors are most common in fair-skinned individuals with a history of excessive sun exposure and sunburns. Melanoma
    • Neuroendocrine
  • Diagnosis:
    • CT/ PET PET An imaging technique that combines a positron-emission tomography (PET) scanner and a ct X ray scanner. This establishes a precise anatomic localization in the same session. Nuclear Imaging scan while staging Staging Methods which attempt to express in replicable terms the extent of the neoplasm in the patient. Grading, Staging, and Metastasis the primary tumor Tumor Inflammation
    • Imaging usually shows multiple tumors with well-defined (noninfiltrative) borders.
    • Often with central umbilication due to central necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage
  • Management: 
    • Depends on the primary cancer site
    • Common treatment modalities:
      • Chemotherapy Chemotherapy Osteosarcoma
      • Targeted therapy Targeted Therapy Targeted therapy exerts antineoplastic activity against cancer cells by interfering with unique properties found in tumors or malignancies. The types of drugs can be small molecules, which are able to enter cells, or monoclonal antibodies, which have targets outside of or on the surface of cells. Targeted and Other Nontraditional Antineoplastic Therapy with monoclonal antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions
      • Immunotherapy 
    • Metastasectomy:
      • May be appropriate for some cancers:
        • For curative attempts
        • To reduce tumor burden Tumor burden The total amount (cell number, weight, size or volume) of tumor cells or tissue in the body. Tumor Lysis Syndrome and prolong survival in select tumors
      • Colorectal cancer Colorectal cancer Colorectal cancer (CRC) is the 2nd leading cause of cancer-related deaths in the United States. Colorectal cancer is a heterogeneous disease that arises from genetic and epigenetic abnormalities, with influence from environmental factors. Colorectal Cancer: The standard of care Standard of care The minimum acceptable patient care, based on statutes, court decisions, policies, or professional guidelines. Malpractice in select patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship is resection or ablation of colorectal liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy metastases (CRLM).
      • The 5-year survival rate for patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with resectable CRLM has doubled from 30% to 60% in the last 2 decades.
Metastases in the liver

Gross specimen of the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy showing multiple metastatic tumors

Image: “Secondary tumor Tumor Inflammation deposits in the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy from a primary cancer of the pancreas Pancreas The pancreas lies mostly posterior to the stomach and extends across the posterior abdominal wall from the duodenum on the right to the spleen on the left. This organ has both exocrine and endocrine tissue. Pancreas: Anatomy” by John Hayman. License: Public Domain

Differential Diagnosis

The following are important differential diagnoses of a solid mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast in the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy:

Benign Benign Fibroadenoma lesions:

  • Hepatic hemangioma Hemangioma A vascular anomaly due to proliferation of blood vessels that forms a tumor-like mass. The common types involve capillaries and veins. It can occur anywhere in the body but is most frequently noticed in the skin and subcutaneous tissue. Imaging of the Liver and Biliary Tract (also known as “cavernous hemangioma Hemangioma A vascular anomaly due to proliferation of blood vessels that forms a tumor-like mass. The common types involve capillaries and veins. It can occur anywhere in the body but is most frequently noticed in the skin and subcutaneous tissue. Imaging of the Liver and Biliary Tract”): the most common benign Benign Fibroadenoma liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy lesion. Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency is higher in women than men. Presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor is usually asymptomatic and the prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas is excellent.
  • Focal nodular hyperplasia Focal nodular hyperplasia Solitary or multiple benign hepatic vascular tumors, usually occurring in women of 20-50 years of age. The nodule, poorly encapsulated, consists of a central stellate fibrous scar and normal liver elements such as hepatocytes, small bile ducts, and kupffer cells among the intervening fibrous septa. The pale colored central scar represents large blood vessels with hyperplastic fibromuscular layer and narrowing lumen. Benign Liver Tumors (FNH): a proliferation of hyperplastic Hyperplastic Colon Polyps hepatocytes Hepatocytes The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. Liver: Anatomy surrounding a central stellate scar Scar Dermatologic Examination. Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency is higher in women than men.
  • Hepatocellular adenoma Hepatocellular adenoma A benign epithelial tumor of the liver. Benign Liver Tumors ( hepatic adenoma Hepatic adenoma A benign epithelial tumor of the liver. Benign Liver Tumors): solitary lesions developing in the normal liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy of young women using estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy medications, and patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with glycogen storage disease Glycogen storage disease A group of inherited metabolic disorders involving the enzymes responsible for the synthesis and degradation of glycogen. In some patients, prominent liver involvement is presented. In others, more generalized storage of glycogen occurs, sometimes with prominent cardiac involvement. Benign Liver Tumors or metabolic syndrome Metabolic syndrome Metabolic syndrome is a cluster of conditions that significantly increases the risk for several secondary diseases, notably cardiovascular disease, type 2 diabetes, and nonalcoholic fatty liver. In general, it is agreed that hypertension, insulin resistance/hyperglycemia, and hyperlipidemia, along with central obesity, are components of the metabolic syndrome. Metabolic Syndrome.
  • Regenerative nodules: proliferations of hepatocytes Hepatocytes The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. Liver: Anatomy and stroma usually seen in cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis as a response to liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy injury.

Malignant lesions:

Cholangiocarcinoma Cholangiocarcinoma A malignant tumor arising from the epithelium of the bile ducts. Rare Malignant Liver Tumors ( bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy duct cancer): arises from epithelial cells of the intrahepatic and extrahepatic bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy ducts. Risk factors in the United States include primary sclerosing cholangitis Primary Sclerosing Cholangitis Primary sclerosing cholangitis (PSC) is an inflammatory disease that causes fibrosis and strictures of the bile ducts. The exact etiology is unknown, but there is a strong association with IBD. Patients typically present with an insidious onset of fatigue, pruritus, and jaundice, which can progress to cirrhosis and complications related to biliary obstruction. Primary Sclerosing Cholangitis and fibropolycystic liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy disease (e.g., choledochal cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change). Hepatolithiasis Hepatolithiasis Rare Malignant Liver Tumors (recurrent pyogenic cholangitis) is the biggest risk factor for cholangiocarcinoma Cholangiocarcinoma A malignant tumor arising from the epithelium of the bile ducts. Rare Malignant Liver Tumors in Asia ASIA Spinal Cord Injuries.

References

  1. Gill, R.M., Kakar S. (2020). Liver and Gallbladder. In Kumar, V., Abbas, A. K., Aster, J.C., (Eds.), Robbins & Cotran Pathologic Basis of Disease. 10th ed. pp. 868–872. Elsevier, Inc.
  2. Schwartz, J.M., Carithers, R.L. (2020). Epidemiology and risk factors for hepatocellular carcinoma. UpToDate. Retrieved November 8, 2020, from https://www.uptodate.com/contents/epidemiology-and-risk-factors-for-hepatocellular-carcinoma
  3. Schwartz, J.M., Carithers, R.L., Sirlin, C.B. (2019). Clinical features and diagnosis of hepatocellular carcinoma. UpToDate. Retrieved November 9, 2020, from https://www.uptodate.com/contents/clinical-features-and-diagnosis-of-hepatocellular-carcinoma
  4. The Global Cancer Observatory. (2020). Number of new cases of cancer in the U.S.A. Globoscan 2018. International Agency of Research on Cancer, World Health Organization. Retrieved on November 8, 2020, from https://gco.iarc.fr/today/data/factsheets/populations/840-united-states-of-america-fact-sheets.pdf
  5. Sempokuya, T., Wong, L.L. (2019). Ten-year survival and recurrence of hepatocellular cancer. Hepatoma Research. 5, 38. https://doi.org/10.20517/2394-5079.2019.013

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