Cholangiocarcinoma - AbsoluteAstronomy.com

Cholangiocarcinoma is a cancer

Cancer

Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

of the bile duct

Bile duct

A bile duct is any of a number of long tube-like structures that carry bile.Bile, required for the digestion of food, is excreted by the liver into passages that carry bile toward the hepatic duct, which joins with the cystic duct to form the common bile duct, which opens into the intestine.The...

s which drain bile

Bile

Bile or gall is a bitter-tasting, dark green to yellowish brown fluid, produced by the liver of most vertebrates, that aids the process of digestion of lipids in the small intestine. In many species, bile is stored in the gallbladder and upon eating is discharged into the duodenum...

from the liver

Liver

The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...

into the small intestine

Small intestine

The small intestine is the part of the gastrointestinal tract following the stomach and followed by the large intestine, and is where much of the digestion and absorption of food takes place. In invertebrates such as worms, the terms "gastrointestinal tract" and "large intestine" are often used to...

. Other biliary tract cancers include pancreatic cancer

Pancreatic cancer

Pancreatic cancer refers to a malignant neoplasm of the pancreas. The most common type of pancreatic cancer, accounting for 95% of these tumors is adenocarcinoma, which arises within the exocrine component of the pancreas. A minority arises from the islet cells and is classified as a...

, gallbladder cancer

Gallbladder cancer

Gallbladder cancer is a relatively uncommon cancer. It has peculiar geographical distribution being common in central and South America, central and eastern Europe, Japan and northern India; it is also common in certain ethnic groups e.g. Native American Indians and Hispanics. If it is diagnosed...

, and cancer of the ampulla of Vater. Cholangiocarcinoma is a relatively rare adenocarcinoma

Adenocarcinoma

Adenocarcinoma is a cancer of an epithelium that originates in glandular tissue. Epithelial tissue includes, but is not limited to, the surface layer of skin, glands and a variety of other tissue that lines the cavities and organs of the body. Epithelium can be derived embryologically from...

(glandular cancer), with an annual incidence

Incidence (epidemiology)

Incidence is a measure of the risk of developing some new condition within a specified period of time. Although sometimes loosely expressed simply as the number of new cases during some time period, it is better expressed as a proportion or a rate with a denominator.Incidence proportion is the...

of 1–2 cases per 100,000 in the Western world, but rates of cholangiocarcinoma have been rising worldwide over the past several decades.

Prominent symptoms of cholangiocarcinoma include abnormal liver function tests, abdominal pain

Abdominal pain

Abdominal pain can be one of the symptoms associated with transient disorders or serious disease. Making a definitive diagnosis of the cause of abdominal pain can be difficult, because many diseases can result in this symptom. Abdominal pain is a common problem...

, jaundice

Jaundice

Jaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...

, weight loss

Weight loss

Weight loss, in the context of medicine, health or physical fitness, is a reduction of the total body mass, due to a mean loss of fluid, body fat or adipose tissue and/or lean mass, namely bone mineral deposits, muscle, tendon and other connective tissue...

, and sometimes generalized itching, fever

Fever

Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...

, or changes in stool

Human feces

Human feces , also known as a stool, is the waste product of the human digestive system including bacteria. It varies significantly in appearance, according to the state of the digestive system, diet and general health....

or urine

Urine

Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...

color. The disease is diagnosed through a combination of blood test

Blood test

A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a needle, or via fingerprick....

s, imaging, endoscopy

Endoscopy

Endoscopy means looking inside and typically refers to looking inside the body for medical reasons using an endoscope , an instrument used to examine the interior of a hollow organ or cavity of the body. Unlike most other medical imaging devices, endoscopes are inserted directly into the organ...

, and sometimes surgical exploration. Known risk factors for cholangiocarcinoma include primary sclerosing cholangitis

Primary sclerosing cholangitis

Primary sclerosing cholangitis is a chronic liver disease caused by progressive inflammation and scarring of the bile ducts of the liver. The inflammation impedes the flow of bile to the gut, which can ultimately lead to liver cirrhosis, liver failure and liver cancer...

(an inflammatory disease of the bile ducts), congenital liver malformations, infection with the parasitic liver fluke

Liver fluke

Liver flukes are a polyphyletic group of trematodes .Adults of liver flukes are localized in the liver of various mammals, including humans. These flatworms can occur in bile ducts, gallbladder, and liver parenchyma. They feed on blood...

s Opisthorchis viverrini
Opisthorchis viverrini
Opisthorchis viverrini, common name Southeast Asian liver fluke, is a trematode parasite from the family Opisthorchiidae that attacks the area of the bile duct. Infection is acquired when people ingest raw or undercooked fish. It causes the disease opisthorchiasis...

or Clonorchis sinensis
Clonorchis sinensis
Clonorchis sinensis, the Chinese liver fluke, is a human liver fluke in the class Trematoda, Phylum Platyhelminthes. This parasite lives in the liver of humans, and is found mainly in the common bile duct and gall bladder, feeding on bile...

, and exposure to Thorotrast

Thorotrast

Thorotrast is a suspension containing particles of the radioactive compound thorium dioxide, ThO2, used as a contrast medium in X-ray diagnostics in the 1930s and 40s ....

(thorium dioxide

Thorium dioxide

Thorium dioxide , also called thorium oxide is a white, crystalline powder. It was formerly known as thoria or thorina. It is produced mainly as a by-product of lanthanide and uranium production.[1]...

), a chemical formerly used in medical imaging

Medical imaging

Medical imaging is the technique and process used to create images of the human body for clinical purposes or medical science...

. However, most patients with cholangiocarcinoma have no specific risk factors.

Cholangiocarcinoma is considered to be an incurable and rapidly lethal

Lethal

Lethal is an adjective meaning capable of causing death.Lethal may also refer to:* Lethal , an American heavy metal band* Leigh Matthews, Australian rules footballer nicknamed "Lethal" or "Lethal" Leigh...

disease unless all of its tumors can be fully resected

Segmental resection

Segmental resection is a surgical procedure to remove part of an organ or gland. It may also be used to remove a tumor and normal tissue around it. In lung cancer surgery, segmental resection refers to removing a section of a lobe of the lung.- External links :* entry in the public domain NCI...

(cut out surgically). There is no potentially curative treatment except surgery, but most patients have advanced

Cancer staging

The stage of a cancer is a description of the extent the cancer has spread. The stage often takes into account the size of a tumor, how deeply it has penetrated, whether it has invaded adjacent organs, how many lymph nodes it has metastasized to , and whether it has spread to distant organs...

because of this inoperable disease after diagnosis. Patients with cholangiocarcinoma are generally managed, though never cured, with chemotherapy

Chemotherapy

Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....

or radiation therapy

Radiation therapy

Radiation therapy , radiation oncology, or radiotherapy , sometimes abbreviated to XRT or DXT, is the medical use of ionizing radiation, generally as part of cancer treatment to control malignant cells.Radiation therapy is commonly applied to the cancerous tumor because of its ability to control...

as well as palliative care

Palliative care

Palliative care is a specialized area of healthcare that focuses on relieving and preventing the suffering of patients...

measures, and these are also used as adjuvant therapies post-surgically in cases where resection has been successful. Some areas of ongoing medical research in cholangiocarcinoma include the use of newer targeted therapies

Targeted therapy

Targeted therapy is a type of medication that blocks the growth of cancer cells by interfering with specific targeted molecules needed for carcinogenesis and tumor growth, rather than by simply interfering with rapidly dividing cells...

(such as erlotinib

Erlotinib

Erlotinib hydrochloride is a drug used to treat non-small cell lung cancer, pancreatic cancer and several other types of cancer. It is a reversible tyrosine kinase inhibitor, which acts on the epidermal growth factor receptor . It is marketed in the United States by Genentech and OSI...

) or photodynamic therapy

Photodynamic therapy

Photodynamic therapy is used clinically to treat a wide range of medical conditions, including malignant cancers, and is recognised as a treatment strategy which is both minimally invasive and minimally toxic...

for treatment, and the concentration of byproducts of cancer stromal cell

Stromal cell

In cell biology, stromal cells are connective tissue cells of any organ, for example in the uterine mucosa , prostate, bone marrow, and the ovary. They are cells that support the function of the parenchymal cells of that organ...

formation in the blood for diagnosis

Medical diagnosis

Medical diagnosis refers both to the process of attempting to determine or identify a possible disease or disorder , and to the opinion reached by this process...

Staging

Although there are at least three staging systems

Cancer staging

for cholangiocarcinoma (e.g. Bismuth, Blumgart, American Joint Committee on Cancer

American Joint Committee on Cancer

The American Joint Committee on Cancer is an organization best known for defining and popularizing cancer staging standards, officially the AJCC staging system....

) none have been shown to be useful in predicting survival. The most important staging issue is whether the tumor can be surgically removed

Segmental resection

, or whether it is too advanced or invasive for surgical treatment. Often, this determination can only be made at the time of surgery.

General guidelines for operability include:

Absence of lymph node
Lymph node
A lymph node is a small ball or an oval-shaped organ of the immune system, distributed widely throughout the body including the armpit and stomach/gut and linked by lymphatic vessels. Lymph nodes are garrisons of B, T, and other immune cells. Lymph nodes are found all through the body, and act as...

or liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...

metastases
Metastasis
Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...
Absence of involvement of the portal vein
Hepatic portal vein
The hepatic portal vein is not a true vein, because it does not conduct blood directly to the heart. It is a vessel in the abdominal cavity that drains blood from the gastrointestinal tract and spleen to capillary beds in the liver...
Absence of direct invasion of adjacent organs
Absence of widespread metastatic disease

Signs and symptoms

The most common physical indications of cholangiocarcinoma are abnormal liver function tests

Liver function tests

Liver function tests , are groups of clinical biochemistry laboratory blood assays designed to give information about the state of a patient's liver. The parameters measured include PT/INR, aPTT, albumin, billirubin and others...

, jaundice

Jaundice

(yellowing of the eyes and skin), which occurs only, when bile ducts are blocked by the tumor, abdominal pain

Abdominal pain

(30%–50%), generalized itching (66%), weight loss

Weight loss

(30%–50%), fever

Fever

(up to 20%), or changes in stool

Human feces

or urine

Urine

color. To some extent, the symptoms depend upon the location of the tumor: Patients with cholangiocarcinoma in the extrahepatic bile ducts (outside the liver) are more likely to have jaundice, while those with tumors of the bile ducts within the liver often have pain without jaundice.

Blood tests of liver function

Liver function tests

in patients with cholangiocarcinoma often reveal a so-called "obstructive picture," with elevated bilirubin

Bilirubin

Bilirubin is the yellow breakdown product of normal heme catabolism. Heme is found in hemoglobin, a principal component of red blood cells. Bilirubin is excreted in bile and urine, and elevated levels may indicate certain diseases...

, alkaline phosphatase

Alkaline phosphatase

Alkaline phosphatase is a hydrolase enzyme responsible for removing phosphate groups from many types of molecules, including nucleotides, proteins, and alkaloids. The process of removing the phosphate group is called dephosphorylation...

, and gamma glutamyl transferase levels, and relatively normal transaminase

Transaminase

In biochemistry, a transaminase or an aminotransferase is an enzyme that catalyzes a type of reaction between an amino acid and an α-keto acid. To be specific, this reaction involves removing the amino group from the amino acid, leaving behind an α-keto acid, and transferring it to the...

levels. Such laboratory findings suggest obstruction of the bile ducts, rather than inflammation

Inflammation

Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...

or infection of the liver, as the primary cause of the jaundice. CA19-9

CA19-9

CA19-9 is a tumor marker that is used primarily in the management of pancreatic cancer.-History:...

is elevated in most cases.

Risk factors

Although most patients present without any known risk factors evident, a number of risk factor

Risk factor

In epidemiology, a risk factor is a variable associated with an increased risk of disease or infection. Sometimes, determinant is also used, being a variable associated with either increased or decreased risk.-Correlation vs causation:...

s for the development of cholangiocarcinoma have been described; in the Western world, the most common of these is primary sclerosing cholangitis

Primary sclerosing cholangitis

(PSC), an inflammatory disease of the bile ducts which is in turn closely associated with ulcerative colitis

Ulcerative colitis

Ulcerative colitis is a form of inflammatory bowel disease . Ulcerative colitis is a form of colitis, a disease of the colon , that includes characteristic ulcers, or open sores. The main symptom of active disease is usually constant diarrhea mixed with blood, of gradual onset...

(UC). Epidemiologic studies have suggested that the lifetime risk of developing cholangiocarcinoma for a person with PSC is 10%–15%, although autopsy series have found rates as high as 30% in this population. The mechanism by which PSC increases the risk of cholangiocarcinoma is not well understood.

Certain parasitic liver diseases

Parasitic disease

A parasitic disease is an infectious disease caused or transmitted by a parasite. Many parasites do not cause diseases. Parasitic diseases can affect practically all living organisms, including plants and mammals...

may be risk factors as well. Colonization with the liver fluke

Liver fluke

Thailand

Thailand , officially the Kingdom of Thailand , formerly known as Siam , is a country located at the centre of the Indochina peninsula and Southeast Asia. It is bordered to the north by Burma and Laos, to the east by Laos and Cambodia, to the south by the Gulf of Thailand and Malaysia, and to the...

, Laos

Laos

Laos Lao: ສາທາລະນະລັດ ປະຊາທິປະໄຕ ປະຊາຊົນລາວ Sathalanalat Paxathipatai Paxaxon Lao, officially the Lao People's Democratic Republic, is a landlocked country in Southeast Asia, bordered by Burma and China to the northwest, Vietnam to the east, Cambodia to the south and Thailand to the west...

, and Malaysia) or Clonorchis sinensis
Clonorchis sinensis
Clonorchis sinensis, the Chinese liver fluke, is a human liver fluke in the class Trematoda, Phylum Platyhelminthes. This parasite lives in the liver of humans, and is found mainly in the common bile duct and gall bladder, feeding on bile...

(found in Japan

Japan

Japan is an island nation in East Asia. Located in the Pacific Ocean, it lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south...

, Korea

Korea

Korea ) is an East Asian geographic region that is currently divided into two separate sovereign states — North Korea and South Korea. Located on the Korean Peninsula, Korea is bordered by the People's Republic of China to the northwest, Russia to the northeast, and is separated from Japan to the...

, and Vietnam

Vietnam

Vietnam – sometimes spelled Viet Nam , officially the Socialist Republic of Vietnam – is the easternmost country on the Indochina Peninsula in Southeast Asia. It is bordered by China to the north, Laos to the northwest, Cambodia to the southwest, and the South China Sea –...

) has been associated with the development of cholangiocarcinoma. Patients with chronic liver disease, whether in the form of viral hepatitis (e.g. hepatitis B or C

Hepatitis C

Hepatitis C is an infectious disease primarily affecting the liver, caused by the hepatitis C virus . The infection is often asymptomatic, but chronic infection can lead to scarring of the liver and ultimately to cirrhosis, which is generally apparent after many years...

), alcoholic liver disease

Alcoholic liver disease

Alcoholic liver disease is a term that encompasses the hepatic manifestations of alcohol overconsumption, including fatty liver, alcoholic hepatitis, and chronic hepatitis with hepatic fibrosis or cirrhosis. It is the major cause of liver disease in Western countries...

, or cirrhosis

Cirrhosis

Cirrhosis is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrosis, scar tissue and regenerative nodules , leading to loss of liver function...

from other causes, are at increased risk of cholangiocarcinoma. HIV infection was also identified in one study as a potential risk factor for cholangiocarcinoma, although it was unclear whether HIV

HIV

Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...

itself or correlated factors (e.g. hepatitis C infection) were responsible for the association.

Congenital

Congenital disorder

A congenital disorder, or congenital disease, is a condition existing at birth and often before birth, or that develops during the first month of life , regardless of causation...

liver abnormalities, such as Caroli's syndrome or choledochal cysts, have been associated with an approximately 15% lifetime risk of developing cholangiocarcinoma. The rare inherited disorders Lynch syndrome II and biliary papillomatosis are associated with cholangiocarcinoma. The presence of gallstones (cholelithiasis) is not clearly associated with cholangiocarcinoma. However, intrahepatic stones (so-called hepatolithiasis

Hepatolithiasis

Hepatolithiasis is the presence of gallstones in the biliary ducts of the liver. Treatment is usually surgical. It is rare in Western countries, but prevalent in East Asia....

), which are rare in the West but common in parts of Asia, have been strongly associated with cholangiocarcinoma. Exposure to Thorotrast

Thorotrast

Thorotrast is a suspension containing particles of the radioactive compound thorium dioxide, ThO2, used as a contrast medium in X-ray diagnostics in the 1930s and 40s ....

, a form of thorium dioxide

Thorium dioxide

which was used as a radiologic contrast medium

Radiocontrast

Radiocontrast agents are a type of medical contrast medium used to improve the visibility of internal bodily structures in an X-ray based imaging techniques such as computed tomography or radiography...

, has been linked to the development of cholangiocarcinoma as late as 30–40 years after exposure; Thorotrast was banned in the United States in the 1950s due to its carcinogenicity.

Pathophysiology

Cholangiocarcinoma can affect any area of the bile ducts, either within or outside the liver. Tumors occurring in the bile ducts within the liver are referred to as intrahepatic, those occurring in the ducts outside the liver are extrahepatic; and tumors occurring at the site where the bile ducts exit the liver may be referred to as perihilar. A cholangiocarcinoma occurring at the junction where the left and right hepatic ducts meet to form the common bile duct

Common bile duct

The common bile duct is a tube-like anatomic structure in the human gastrointestinal tract. It is formed by the union of the common hepatic duct and the cystic duct . It is later joined by the pancreatic duct to form the ampulla of Vater...

may be referred to eponym

Eponym

An eponym is the name of a person or thing, whether real or fictitious, after which a particular place, tribe, era, discovery, or other item is named or thought to be named...

ously as a Klatskin tumor

Klatskin tumor

A Klatskin tumor is a cholangiocarcinoma occurring at the confluence of the right and left hepatic bile ducts...

.

Although cholangiocarcinoma is known to be an adenocarcinoma

Adenocarcinoma

of the epithelial cells lining the biliary tract, the actual cell of origin is unknown, although recent evidence has suggested that it may arise from a pluripotent hepatic stem cell

Adult stem cell

Adult stem cells are undifferentiated cells, found throughout the body after embryonic development, that multiply by cell division to replenish dying cells and regenerate damaged tissues...

. Cholangiocarcinoma is thought to develop through a series of stages — from early hyperplasia

Hyperplasia

Hyperplasia means increase in number of cells/proliferation of cells. It may result in the gross enlargement of an organ and the term is sometimes mixed with benign neoplasia/ benign tumor....

and metaplasia

Metaplasia

Metaplasia is the reversible replacement of one differentiated cell type with another mature differentiated cell type. The change from one type of cell to another may generally be a part of normal maturation process or caused by some sort of abnormal stimulus...

, through dysplasia

Dysplasia

Dysplasia , is a term used in pathology to refer to an abnormality of development. This generally consists of an expansion of immature cells, with a corresponding decrease in the number and location of mature cells. Dysplasia is often indicative of an early neoplastic process...

, to the development of frank carcinoma

Carcinoma

Carcinoma is the medical term for the most common type of cancer occurring in humans. Put simply, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that generally arises from cells originating in the endodermal or ectodermal germ layer during...

— in a process similar to that seen in the development of colon cancer. Chronic inflammation

Inflammation

and obstruction of the bile ducts, and the resulting impaired bile flow, are thought to play a role in this progression.

Histologically

Histology

Histology is the study of the microscopic anatomy of cells and tissues of plants and animals. It is performed by examining cells and tissues commonly by sectioning and staining; followed by examination under a light microscope or electron microscope...

, cholangiocarcinomas may vary from undifferentiated to well-differentiated

Cellular differentiation

In developmental biology, cellular differentiation is the process by which a less specialized cell becomes a more specialized cell type. Differentiation occurs numerous times during the development of a multicellular organism as the organism changes from a simple zygote to a complex system of...

. They are often surrounded by a brisk fibrotic

Fibrosis

Fibrosis is the formation of excess fibrous connective tissue in an organ or tissue in a reparative or reactive process. This is as opposed to formation of fibrous tissue as a normal constituent of an organ or tissue...

or desmoplastic tissue response; in the presence of extensive fibrosis, it can be difficult to distinguish well-differentiated cholangiocarcinoma from normal reactive epithelium

Epithelium

Epithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands. Functions of epithelial cells include secretion, selective...

. There is no entirely specific immunohistochemical

Immunohistochemistry

Immunohistochemistry or IHC refers to the process of detecting antigens in cells of a tissue section by exploiting the principle of antibodies binding specifically to antigens in biological tissues. IHC takes its name from the roots "immuno," in reference to antibodies used in the procedure, and...

stain that can distinguish malignant

Malignant

Malignancy is the tendency of a medical condition, especially tumors, to become progressively worse and to potentially result in death. Malignancy in cancers is characterized by anaplasia, invasiveness, and metastasis...

from benign

Benign

A benign tumor is a tumor that lacks the ability to metastasize. Common examples of benign tumors include moles and uterine fibroids.The term "benign" implies a mild and nonprogressive disease. Indeed, many kinds of benign tumors are harmless to human health...

biliary ductal tissue, although staining for cytokeratin

Cytokeratin

Cytokeratins are proteins of keratin-containing intermediate filaments found in the intracytoplasmic cytoskeleton of epithelial tissue. The term "cytokeratin" began to be used in the late 1970s when the protein subunits of keratin intermediate filaments inside cells were first being identified and...

s, carcinoembryonic antigen

Carcinoembryonic antigen

Carcinoembryonic antigen is a glycoprotein involved in cell adhesion. It is normally produced during fetal development, but the production of CEA stops before birth. Therefore, it is not usually present in the blood of healthy adults, although levels are raised in heavy smokers...

, and mucin

Mucin

Mucins are a family of high molecular weight, heavily glycosylated proteins produced by epithelial tissues in most metazoans. Mucins' key characteristic is their ability to form gels; therefore they are a key component in most gel-like secretions, serving functions from lubrication to cell...

s may aid in diagnosis. Most tumors (>90%) are adenocarcinoma

Adenocarcinoma

Diagnosis

Cholangiocarcinoma is definitively diagnosed from tissue, i.e. it is proven by biopsy

Biopsy

A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...

or examination of the tissue excised at surgery. It may be suspected in a patient with obstructive jaundice. Considering it as the working diagnosis may be challenging in patients with primary sclerosing cholangitis (PSC); such patients are at high risk of developing cholangiocarcinoma, but the symptoms may be difficult to distinguish from those of PSC. Furthermore, in patients with PSC, such diagnostic clues as a visible mass on imaging or biliary ductal dilatation may not be evident.

Blood tests

There are no specific blood test

Blood test

A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a needle, or via fingerprick....

s that can diagnose cholangiocarcinoma by themselves. Serum levels of carcinoembryonic antigen

Carcinoembryonic antigen

(CEA) and CA19-9 are often elevated, but are not sensitive or specific enough to be used as a general screening

Screening (medicine)

Screening, in medicine, is a strategy used in a population to detect a disease in individuals without signs or symptoms of that disease. Unlike what generally happens in medicine, screening tests are performed on persons without any clinical sign of disease....

tool. However, they may be useful in conjunction with imaging methods

Medical imaging

Medical imaging is the technique and process used to create images of the human body for clinical purposes or medical science...

in supporting a suspected diagnosis of cholangiocarcinoma.

Abdominal imaging

Ultrasound

Ultrasound is cyclic sound pressure with a frequency greater than the upper limit of human hearing. Ultrasound is thus not separated from "normal" sound based on differences in physical properties, only the fact that humans cannot hear it. Although this limit varies from person to person, it is...

of the liver

Liver

and biliary tree

Biliary tree

The biliary tract is the common anatomical term for the path by which bile is secreted by the liver then transported to the first part of the small intestine, also known as the duodenum...

is often used as the initial imaging modality in patients with suspected obstructive jaundice. Ultrasound can identify obstruction and ductal dilatation and, in some cases, may be sufficient to diagnose cholangiocarcinoma. Computed tomography

Computed tomography

X-ray computed tomography or Computer tomography , is a medical imaging method employing tomography created by computer processing...

(CT) scanning may also play an important role in the diagnosis of cholangiocarcinoma.

Imaging of the biliary tree

While abdominal imaging can be useful in the diagnosis of cholangiocarcinoma, direct imaging of the bile duct

Bile duct

s is often necessary. Endoscopic retrograde cholangiopancreatography

Endoscopic retrograde cholangiopancreatography

Endoscopic retrograde cholangiopancreatography is a technique that combines the use of endoscopy and fluoroscopy to diagnose and treat certain problems of the biliary or pancreatic ductal systems...

(ERCP), an endoscopic

Endoscopy

procedure performed by a gastroenterologist or specially trained surgeon, has been widely used for this purpose. Although ERCP is an invasive procedure with attendant risks, its advantages include the ability to obtain biopsies

Biopsy

and to place stent

Stent

In the technical vocabulary of medicine, a stent is an artificial 'tube' inserted into a natural passage/conduit in the body to prevent, or counteract, a disease-induced, localized flow constriction. The term may also refer to a tube used to temporarily hold such a natural conduit open to allow...

s or perform other interventions to relieve biliary obstruction. Endoscopic ultrasound

Endoscopic ultrasound

Endoscopic ultrasound or echo-endoscopy is a medical procedure in endoscopy is combined with ultrasound to obtain images of the internal organs in the chest and abdomen. It can be used to visualize the wall of these organs, or to look at adjacent structures...

can also be performed at the time of ERCP and may increase the accuracy of the biopsy and yield information on lymph node

Lymph node

A lymph node is a small ball or an oval-shaped organ of the immune system, distributed widely throughout the body including the armpit and stomach/gut and linked by lymphatic vessels. Lymph nodes are garrisons of B, T, and other immune cells. Lymph nodes are found all through the body, and act as...

invasion and operability. As an alternative to ERCP, percutaneous transhepatic cholangiography

Percutaneous transhepatic cholangiography

Percutaneous transhepatic cholangiography or percutaneous hepatic cholangiogram is a radiologic technique used to visualize the anatomy of the biliary tract. A contrast medium is injected into a bile duct in the liver, after which X-rays are taken...

(PTC) may be utilized. Magnetic resonance cholangiopancreatography

Magnetic resonance cholangiopancreatography

Magnetic resonance cholangiopancreatography is a medical imaging technique that uses magnetic resonance imaging to visualise the biliary and pancreatic ducts in a non-invasive manner...

(MRCP) is a non-invasive alternative to ERCP. Some authors have suggested that MRCP should supplant ERCP in the diagnosis of biliary cancers, as it may more accurately define the tumor and avoids the risks of ERCP.

Surgery

Surgical exploration

Surgery

Surgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, or to help improve bodily function or appearance.An act of performing surgery may be called a surgical...

may be necessary to obtain a suitable biopsy

Biopsy

and to accurately stage

Cancer staging

a patient with cholangiocarcinoma. Laparoscopy

Laparoscopy

Laparoscopy is an operation performed in the abdomen or pelvis through small incisions with the aid of a camera...

can be used for staging purposes and may avoid the need for a more invasive surgical procedure, such as laparotomy

Laparotomy

A laparotomy is a surgical procedure involving a large incision through the abdominal wall to gain access into the abdominal cavity. It is also known as coeliotomy.- Terminology :...

, in some patients. Surgery is also the only curative option for cholangiocarcinoma, although it is limited to patients with early-stage disease.

Pathology

Histologically, cholangiocarcinomas are classically well to moderately differentiated. Immunohistochemistry

Immunohistochemistry

is useful in the diagnosis and can be used to differentiate a cholangiocarcinoma primary tumor from metastasis of most other gastrointestinal tumors. Cytological scrapings are often nondiagnostic.

Treatment

Cholangiocarcinoma is considered to be an incurable and rapidly lethal disease unless all the tumors can be fully resected

Segmental resection

(that is, cut out surgically). Since the operability of the tumor can only be assessed during surgery in most cases, a majority of patients undergo exploratory surgery unless there is already a clear indication that the tumor is inoperable.

Adjuvant therapy followed by liver transplantation

Liver transplantation

Liver transplantation or hepatic transplantation is the replacement of a diseased liver with a healthy liver allograft. The most commonly used technique is orthotopic transplantation, in which the native liver is removed and replaced by the donor organ in the same anatomic location as the original...

may have a role in treatment of certain unresectable cases.

Adjuvant chemotherapy and radiation therapy

If the tumor can be removed surgically, patients may receive adjuvant chemotherapy

Chemotherapy

Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....

or radiation therapy

Radiation therapy

after the operation to improve the chances of cure. If the tissue margins are negative (i.e. the tumor has been totally excised

Excision

Excision is the alias of Jeff Abel, a dubstep DJ and music boss from British Columbia, Canada. He frequently works with fellow Canadian dubstep producers Datsik and Downlink. As one of the first dubstep producers and DJs in North America, he has played a significant role in the genre's growth in...

), adjuvant therapy is of uncertain benefit. Both positive and negative results have been reported with adjuvant radiation therapy in this setting, and no prospective randomized controlled trial

Randomized controlled trial

A randomized controlled trial is a type of scientific experiment - a form of clinical trial - most commonly used in testing the safety and efficacy or effectiveness of healthcare services or health technologies A randomized controlled trial (RCT) is a type of scientific experiment - a form of...

s have been conducted as of March 2007. Adjuvant chemotherapy appears to be ineffective in patients with completely resected tumors. The role of combined chemoradiotherapy in this setting is unclear. However, if the tumor tissue margins are positive, indicating that the tumor was not completely removed via surgery, then adjuvant therapy with radiation and possibly chemotherapy is generally recommended based on the available data.

Treatment of advanced disease

The majority of cases of cholangiocarcinoma present as inoperable (unresectable) disease in which case patients are generally treated with palliative chemotherapy

Chemotherapy

Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....

, with or without radiotherapy. Chemotherapy has been shown in a randomized controlled trial

Randomized controlled trial

to improve quality of life

Quality of life

The term quality of life is used to evaluate the general well-being of individuals and societies. The term is used in a wide range of contexts, including the fields of international development, healthcare, and politics. Quality of life should not be confused with the concept of standard of...

and extend survival in patients with inoperable cholangiocarcinoma. There is no single chemotherapy regimen which is universally used, and enrollment in clinical trial

Clinical trial

Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...

s is often recommended when possible. Chemotherapy agents used to treat cholangiocarcinoma include 5-fluorouracil with leucovorin, gemcitabine as a single agent, or gemcitabine plus cisplatin

Cisplatin

Cisplatin, cisplatinum, or cis-diamminedichloroplatinum is a chemotherapy drug. It is used to treat various types of cancers, including sarcomas, some carcinomas , lymphomas, and germ cell tumors...

, irinotecan

Irinotecan

Irinotecan is a drug used for the treatment of cancer.Irinotecan prevents DNA from unwinding by inhibition of topoisomerase 1. In chemical terms, it is a semisynthetic analogue of the natural alkaloid camptothecin....

, or capecitabine. A small pilot study suggested possible benefit from the tyrosine kinase

Tyrosine kinase

A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to a protein in a cell. It functions as an "on" or "off" switch in many cellular functions....

inhibitor erlotinib

Erlotinib

in patients with advanced cholangiocarcinoma.

Photodynamic therapy

Photodynamic therapy

, an experimental approach in which patients are injected with a light-sensitizing agent and light is then applied endoscopically

Endoscopy

directly to the tumor, has shown promising results compared to supportive care in two small randomized controlled trial

Randomized controlled trial

s. However, its ultimate role in the management of cholangiocarcinoma is unclear at present.
Photodynamic Therapy

Photodynamic therapy

has been shown to improve survival and quality of life

Prognosis

Surgical resection offers the only potential chance of cure in cholangiocarcinoma. For non-resectable cases, the 5-year survival rate is 0% where the disease is inoperable because distal lymph nodes show metastases, and less than 5% in general. Overall median duration of survival is less than 6 months in inoperable, untreated, otherwise healthy patients with tumors involving the liver by way of the intrahepatic bile ducts

Intrahepatic bile ducts

Intrahepatic bile ducts are part of the outflow system of exocrine bile product from the liver.They can be divided into large and small ducts. Examples include:* Large: left and right hepatic ducts* Small: interlobular bile ducts...

and hepatic portal vein

Hepatic portal vein

The hepatic portal vein is not a true vein, because it does not conduct blood directly to the heart. It is a vessel in the abdominal cavity that drains blood from the gastrointestinal tract and spleen to capillary beds in the liver...

.

For surgical cases, the odds of cure vary depending on the tumor location and whether the tumor can be completely, or only partially, removed. Distal cholangiocarcinomas (those arising from the common bile duct

Common bile duct

) are generally treated surgically with a Whipple procedure; long-term survival rates range from 15%–25%, although one series reported a five-year survival of 54% for patients with no involvement of the lymph node

Lymph node

s. Intrahepatic cholangiocarcinomas (those arising from the bile ducts within the liver

Liver

) are usually treated with partial hepatectomy

Hepatectomy

Hepatectomy consists on the surgical resection of the liver. While the term is often employed for the removal of the liver from a liver transplant recipient, this article will focus on partial resections of hepatic tissue.-History:...

. Various series have reported survival estimates after surgery ranging from 22%–66%; the outcome may depend on involvement of lymph nodes and completeness of the surgery. Perihilar cholangiocarcinomas (those occurring near where the bile ducts exit the liver) are least likely to be operable. When surgery is possible, they are generally treated with an aggressive approach often including removal of the gallbladder

Cholecystectomy

Cholecystectomy is the surgical removal of the gallbladder. It is the most common method for treating symptomatic gallstones. Surgical options include the standard procedure, called laparoscopic cholecystectomy, and an older more invasive procedure, called open cholecystectomy.-Open surgery:A...

and potentially part of the liver. In patients with operable perihilar tumors, reported 5-year survival rates range from 20%–50%.

The prognosis

Prognosis

Prognosis is a medical term to describe the likely outcome of an illness.When applied to large statistical populations, prognostic estimates can be very accurate: for example the statement "45% of patients with severe septic shock will die within 28 days" can be made with some confidence, because...

may be worse for patients with primary sclerosing cholangitis who develop cholangiocarcinoma, likely because the cancer is not detected until it is advanced. Some evidence suggests that outcomes may be improving with more aggressive surgical approaches and adjuvant therapy.

Epidemiology

Cholangiocarcinoma is an adenocarcinoma

Adenocarcinoma

of the biliary tract, along with pancreatic cancer

Pancreatic cancer

(which occurs about 20 times more frequently), gall bladder cancer (which occurs twice as often), and cancer of the ampulla of Vater. Treatments and clinical trials for pancreatic cancer, being far more prevalent, are often taken as a starting point for managing cholangiocarcinoma, even though the biologies are different enough that chemotherapies can put pancreatic cancer into permanent remission whereas there are no reports in the literature of long-term survival due to chemotherapy or radiation applied to an inoperable cholangiocarcinoma case.

align="bottom" | *Age-standardized mortality rates from intrahepatic (IC) and extrahepatic (EC) cholangiocarcinoma for men and women, by country. Source: Khan et al., 2002.*
Country	IC (men/women)	EC (men/women)
U.S.A.	0.60 / 0.43	0.70 / 0.87
Japan	0.23 / 0.10	5.87 / 5.20
Australia	0.70 / 0.53	0.90 / 1.23
England/Wales	0.83 / 0.63	0.43 / 0.60
Scotland	1.17 / 1.00	0.60 / 0.73
France	0.27 / 0.20	1.20 / 1.37
Italy	0.13 / 0.13	2.10 / 2.60

Cholangiocarcinoma is a relatively rare form of cancer; each year, approximately 2,000 to 3,000 new cases are diagnosed in the United States, translating into an annual incidence

Incidence (epidemiology)

of 1–2 cases per 100,000 people. Autopsy

Autopsy

An autopsy—also known as a post-mortem examination, necropsy , autopsia cadaverum, or obduction—is a highly specialized surgical procedure that consists of a thorough examination of a corpse to determine the cause and manner of death and to evaluate any disease or injury that may be present...

series have reported a prevalence

Prevalence

In epidemiology, the prevalence of a health-related state in a statistical population is defined as the total number of cases of the risk factor in the population at a given time, or the total number of cases in the population, divided by the number of individuals in the population...

of 0.01% to 0.46%. There is a higher prevalence of cholangiocarcinoma in Asia, which has been attributed to endemic chronic parasitic infestation. The incidence of cholangiocarcinoma increases with age, and the disease is slightly more common in men than in women (possibly due to the higher rate of primary sclerosing cholangitis

Primary sclerosing cholangitis

, a major risk factor, in men). The prevalence of cholangiocarcinoma in patients with primary sclerosing cholangitis may be as high as 30%, based on autopsy studies.

Multiple studies have documented a steady increase in the incidence of intrahepatic cholangiocarcinoma over the past several decades; increases have been seen in North America

North America

North America is a continent wholly within the Northern Hemisphere and almost wholly within the Western Hemisphere. It is also considered a northern subcontinent of the Americas...

, Europe

Europe

Europe is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...

, Asia

Asia

Asia is the world's largest and most populous continent, located primarily in the eastern and northern hemispheres. It covers 8.7% of the Earth's total surface area and with approximately 3.879 billion people, it hosts 60% of the world's current human population...

, and Australia

Australia

Australia , officially the Commonwealth of Australia, is a country in the Southern Hemisphere comprising the mainland of the Australian continent, the island of Tasmania, and numerous smaller islands in the Indian and Pacific Oceans. It is the world's sixth-largest country by total area...

. The reasons for the increasing occurrence of cholangiocarcinoma are unclear; improved diagnostic methods may be partially responsible, but the prevalence of potential risk factors for cholangiocarcinoma, such as HIV infection

HIV

, has also been increasing during this time frame.

External links

American Cancer Society Detailed Guide to Bile Duct Cancer.
Patient information on extrahepatic bile duct tumors, from the National Cancer Institute
National Cancer Institute
The National Cancer Institute is part of the National Institutes of Health , which is one of 11 agencies that are part of the U.S. Department of Health and Human Services. The NCI coordinates the U.S...

.
Cancer.Net: Bile Duct Cancer
The Cholangiocarcinoma Foundation: a resource for patients, friends, caregivers and loved ones of those affected by bile duct cancer.
The Alan Morement Memorial Fund, the UK's only charity dedicated to the disease
Macmillan/Cancerbackup page on Cholangiocarcinoma

The source of this article is wikipedia, the free encyclopedia. The text of this article is licensed under the GFDL.