A liver metastasis is a malignant tumor in the liver that has spread from another organ that is affected by cancer. This can also be called secondary liver cancer or metastatic liver disease. The

liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...

is a common site for metastatic disease because of its rich, dual blood supply (the liver receives blood via the hepatic artery and portal vein). Metastatic tumors in the liver are 20 times more common than primary liver tumors (tumors that originate in the liver). In 50% of all cases the primary tumor is of the

gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the Digestion, digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascula ...

; other common sites include the

breast The breasts are two prominences located on the upper ventral region of the torso among humans and other primates. Both sexes develop breasts from the same embryology, embryological tissues. The relative size and development of the breasts is ...

ovaries The ovary () is a gonad in the female reproductive system that produces ova; when released, an ovum travels through the fallopian tube/oviduct into the uterus. There is an ovary on the left and the right side of the body. The ovaries are endocr ...

bronchus A bronchus ( ; : bronchi, ) is a passage or airway in the lower respiratory tract that conducts air into the lungs. The first or primary bronchi to branch from the trachea at the carina are the right main bronchus and the left main bronchus. T ...

and

kidney In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...

. People with

colorectal cancer Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the Colon (anatomy), colon or rectum (parts of the large intestine). Signs and symptoms may include Lower gastrointestinal ...

are at risk of liver metastases.

Signs and symptoms

The signs and symptoms of secondary liver cancer are usually fairly non-specific (they can also be caused by other things). The following is a list of possible signs and symptoms of liver metastasis: *

Hepatomegaly Hepatomegaly is enlargement of the liver. It is a non-specific sign (medicine), medical sign, having many causes, which can broadly be broken down into infection, hepatic tumours, and metabolic disorder. Often, hepatomegaly presents as an abdomin ...

(liver enlargement) * Tenderness on the right side of the stomach * Cachexic (muscle loss) * Weight loss and low appetite * Ascites (fluid buildup in the stomach area) *

Jaundice Jaundice, also known as icterus, is a yellowish or, less frequently, greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving ...

(yellowing of the skin) * Pyrexia, or fever, in up to 10% of people with liver metastasis Clinical signs include: *Higher levels of alkaline phosphatase ( ALP) and

gamma glutamyl transpeptidase Gamma-glutamyltransferase (also γ-glutamyltransferase, GGT, gamma-GT, gamma-glutamyl transpeptidase; ) is a transferase (a type of enzyme) that catalysis, catalyzes the transfer of gamma-glutamic acid, glutamyl functional groups from molecu ...

(GGT), and positive findings on Ultrasound scan and

CT scan A computed tomography scan (CT scan), formerly called computed axial tomography scan (CAT scan), is a medical imaging technique used to obtain detailed internal images of the body. The personnel that perform CT scans are called radiographers or ...

Causes

Liver metastasis is common in people with metastatic cancer. The rich blood supply in the liver, the role of filtering the blood from the digestive organs lead to the liver, and diverse cell types make the liver a common place for cancer metastasis. Metastases to the liver are more frequently diagnosed in people than primary liver cancers such as

hepatocellular carcinoma Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and is currently the most common cause of death in people with cirrhosis. HCC is the third leading cause of cancer-related deaths worldwide. HCC most common ...

or cholangiocarcinoma. Most hepatic metastases originate from

adenocarcinomas Adenocarcinoma (; plural adenocarcinomas or adenocarcinomata ; AC) is a type of cancerous tumor that can occur in several parts of the body. It is defined as neoplasia of epithelial tissue that has glandular origin, glandular characteristics, o ...

, though other less common types such as

squamous cell carcinoma Squamous-cell carcinoma (SCC), also known as epidermoid carcinoma, comprises a number of different types of cancer that begin in squamous cells. These cells form on the surface of the skin, on the lining of hollow organs in the body, and on the ...

, neuroendocrine tumors,

lymphoma Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). The name typically refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enlarged lymph node ...

sarcoma A sarcoma is a rare type of cancer that arises from cells of mesenchymal origin. Originating from mesenchymal cells means that sarcomas are cancers of connective tissues such as bone, cartilage, muscle, fat, or vascular tissues. Sarcom ...

, and

melanoma Melanoma is the most dangerous type of skin cancer; it develops from the melanin-producing cells known as melanocytes. It typically occurs in the skin, but may rarely occur in the mouth, intestines, or eye (uveal melanoma). In very rare case ...

are also found.

Mechanism

Different cell types in the liver are involved in promoting and then sustaining the cancer metastasis in the liver. Cell types include: Kupffer cells,

parenchymal upright=1.6, Lung parenchyma showing damage due to large subpleural bullae. Parenchyma () is the bulk of functional substance in an animal organ such as the brain or lungs, or a structure such as a tumour. In zoology, it is the tissue that ...

hepatocytes, sinusoidal endothelial cells in the liver,

dendritic cells A dendritic cell (DC) is an antigen-presenting cell (also known as an ''accessory cell'') of the mammalian immune system. A DC's main function is to process antigen material and present it on the cell surface to the T cells of the immune system ...

, and blood based immune cells (

monocytes Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and monocyte-derived dendritic cells. As a part of the vertebrate innate immune system monocytes also i ...

macrophages Macrophages (; abbreviated MPhi, φ, MΦ or MP) are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that ...

, neutrophils). The metastasis develops in four phases:1) microvascular development, 2) pre-angiogenic phase, 3) angiogenic phase (growth of blood vessels), and 4), growth of the tumor phase. Tumor

emboli An embolism is the lodging of an embolus, a blockage-causing piece of material, inside a blood vessel. The embolus may be a blood clot (thrombus), a fat globule (fat embolism), a bubble of air or other gas ( gas embolism), amniotic fluid (amnio ...

entering the sinusoids through the liver blood supply appear to be physically obstructed by the Kupffer cells, but if tumor

are larger, they tend to become lodged in the portal venous branches.

Diagnosis

Imaging such as triple-phase

s or

MRI Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to generate pictures of the anatomy and the physiological processes inside the body. MRI scanners use strong magnetic fields, magnetic field gradients, and rad ...

's are required to evaluate and diagnose a suspected metastasis on the liver. The imaging may also provide information about the source of the primary disease. Other diagnostic criteria include: *

Hemoglobin Hemoglobin (haemoglobin, Hb or Hgb) is a protein containing iron that facilitates the transportation of oxygen in red blood cells. Almost all vertebrates contain hemoglobin, with the sole exception of the fish family Channichthyidae. Hemoglobin ...

decrease *

Liver function test Liver function tests (LFTs or LFs), also referred to as a hepatic panel or liver panel, are groups of blood tests that provide information about the state of a patient's liver. These tests include prothrombin time (PT/INR), activated partial ...

: ALP elevated,

bilirubin Bilirubin (BR) (adopted from German, originally bili—bile—plus ruber—red—from Latin) is a red-orange compound that occurs in the normcomponent of the straw-yellow color in urine. Another breakdown product, stercobilin, causes the brown ...

elevated,

albumin Albumin is a family of globular proteins, the most common of which are the serum albumins. All of the proteins of the albumin family are water- soluble, moderately soluble in concentrated salt solutions, and experience heat denaturation. Alb ...

decrease *

Carcinoembryonic antigen Carcinoembryonic antigen (CEA) describes a set of highly-related glycoproteins involved in cell adhesion. CEA is normally produced in gastrointestinal tissue during fetal development, but the production stops before birth. Consequently, CEA is us ...

for colorectal secondary metastasis * Ultrasound scan *

Biopsy A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, an interventional radiologist, or an interventional cardiology, interventional cardiologist. The process involves the extraction of sampling (medicine), sample ...

under

ultrasound Ultrasound is sound with frequency, frequencies greater than 20 Hertz, kilohertz. This frequency is the approximate upper audible hearing range, limit of human hearing in healthy young adults. The physical principles of acoustic waves apply ...

control Image:Adenocarcinoma liver metastasis.jpg,

Micrograph A micrograph is an image, captured photographically or digitally, taken through a microscope or similar device to show a magnify, magnified image of an object. This is opposed to a macrograph or photomacrograph, an image which is also taken ...

of a

core needle biopsy showing metastatic cancer. File:Secondary tumor deposits in the liver from a primary cancer of the pancreas.jpg, Cross section of a human liver, taken at autopsy examination, showing multiple large pale tumor deposits. The tumor is an adenocarcinoma derived from a primary lesion in the body of the pancreas. File:Metastasis sites for common cancers.svg, Main sites of metastases for some common cancer types, showing liver as the target for many types. Primary cancers are denoted by "''...cancer''" and their main metastasis sites are denoted by "''...metastases''". File:MetstoLiver.png, Metastatic disease to the liver

Treatment

The first line of treatment is surgical resection of the affected tissue( hepatectomy). Other treatments include

chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...

and/or therapies specifically aimed at the liver like

radiofrequency ablation Radiofrequency ablation (RFA), also called fulguration, is a medical procedure in which part of the electrical conduction system of the heart, tumor, sensory nerves or a dysfunctional tissue is ablated using the heat generated from medium fre ...

, transcatheter arterial chemoembolization, selective internal radiation therapy and irreversible electroporation. For most patients no effective treatment exists because both lobes are usually involved, making surgical resection impossible. Younger patients with

metastases Metastasis is a pathogenic agent's spreading from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, ...

from

confined to one lobe of the liver and up to 4 in number may be treated by partial hepatectomy. In selected cases,

may be given systemically or via hepatic artery. In some tumors, notably those arising from the colon and

rectum The rectum (: rectums or recta) is the final straight portion of the large intestine in humans and some other mammals, and the gut in others. Before expulsion through the anus or cloaca, the rectum stores the feces temporarily. The adult ...

, apparently solitary

or metastases to one or other lobes may be resected. A careful search for other

is required, including local recurrence of the original primary tumor (e.g., via

colonoscopy Colonoscopy () or coloscopy () is a medical procedure involving the Endoscopy, endoscopic examination of the large bowel (colon) and the distal portion of the small bowel. This examination is performed using either a Charge-coupled device, CCD ...

) and dissemination elsewhere (e.g., via CT of the

thorax The thorax (: thoraces or thoraxes) or chest is a part of the anatomy of mammals and other tetrapod animals located between the neck and the abdomen. In insects, crustaceans, and the extinct trilobites, the thorax is one of the three main di ...

). 5-year survival rates of 30-40% have been reported following resection. When resection for cure is not possible (R0 resection), percutaneous ethanol injection has been suggested to dehydrate and kill the tumour cells, however there is not enough evidence to determine the effectiveness and safety of this approach. Newer therapeutic approaches include full body ( systemic) therapies, bevacizumab, cetuximab, and

immunomodulator Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as ''activation immunotherapies,'' while immunotherap ...

medications.

Epidemiology

Over 5% of people with primary cancer developed liver metastasis. In 70% to 80% of metastatic colorectal cancer cases, the spread is limited to the liver. The overall survival at 1-year has been estimated to be about 15%. Overall, survival may be lower in people with primary cancer in the testis, breast, prostate, anus, and people with melanoma.

References

External links

{{Medical resources , DiseasesDB = , ICD10 = {{ICD10, Xxx.x , ICD9 = {{ICD9, xxx , ICDO = , OMIM = , MedlinePlus = , MeSH = , GeneReviewsNBK = , GeneReviewsName = , Orphanet = Hepatology Digestive system neoplasia