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Encyclopedia > Cholangiocarcinoma
Cholangiocarcinoma
Classification & external resources
Digestive system diagram showing bile duct location
ICD-10 C22.1
ICD-9 155.1, 156.1
ICD-O: 8160/3
DiseasesDB 2505
MedlinePlus 000291
eMedicine med/343  radio/153
MeSH D018281

Cholangiocarcinoma is a cancer of the bile ducts, which drain bile from the liver into the small intestine. It is a relatively rare cancer, with an annual incidence of 1–2 cases per 100,000 in the Western world,[1] but rates of cholangiocarcinoma have been rising worldwide over the past several decades.[2] Risk factors for cholangiocarcinoma include primary sclerosing cholangitis (an inflammatory disease of the bile ducts), congenital liver malformations, infection with the parasitic liver flukes Opisthorchis viverrini or Clonorchis sinensis, and exposure to Thorotrast (thorium dioxide), a chemical previously used in medical imaging. The symptoms of cholangiocarcinoma include jaundice, weight loss, and sometimes generalized itching. The disease is diagnosed through a combination of blood tests, imaging, endoscopy, and sometimes surgical exploration. Image File history File links Digestive_system_showing_bile_duct. ... The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify diseases and a wide variety of signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or disease. ... The International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) is a coding of diseases and signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or diseases, as classified by the World Health Organization (WHO). ... // C00-D48 - Neoplasms (C00-C14) Malignant neoplasms, lip, oral cavity and pharynx (C00) Malignant neoplasm of lip (C01) Malignant neoplasm of base of tongue (C02) Malignant neoplasm of other and unspecified parts of tongue (C03) Malignant neoplasm of gum (C04) Malignant neoplasm of floor of mouth (C05) Malignant neoplasm of... The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify diseases and a wide variety of signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or disease. ... The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. ... The International Classification of Diseases for Oncology (ICD-O) is a domain specific extension of the International Statistical Classification of Diseases and Related Health Problems for tumor diseases. ... The Disease Bold textDatabase is a free website that provides information about the relationships between medical conditions, symptoms, and medications. ... MedlinePlus (medlineplus. ... eMedicine is an online clinical medical knowledge base that was founded in 1996. ... Medical Subject Headings (MeSH) is a huge controlled vocabulary (or metadata system) for the purpose of indexing journal articles and books in the life sciences. ... Cancer is a class of diseases or disorders characterized by uncontrolled division of cells and the ability of these to spread, either by direct growth into adjacent tissue through invasion, or by implantation into distant sites by metastasis (where cancer cells are transported through the bloodstream or lymphatic system). ... A bile duct is any of a number of long tube-like structures that carry bile. ... Bile (or gall) is a bitter, yellow or green alkaline fluid secreted by hepatocytes from the liver of most vertebrates. ... For the bird, see Liver bird. ... In biology the small intestine is the part of the gastrointestinal tract (gut) between the stomach and the large intestine and includes the duodenum, jejunum, and ileum. ... The incidence of disease is defined as the number of new cases of disease occurring in a population during a defined time interval. ... Primary sclerosing cholangitis (PSC) is a form of cholangitis due to an autoimmune reaction. ... Liver flukes are a polyphyletic group of a trematodes (a kind of flatworm). ... Opisthorchis viverrini - Wikipedia, the free encyclopedia /**/ @import /skins-1. ... }} The Clonorchis sinensis is a human liver fluke in the class Trematoda, Phylum Platyhelminthes. ... Thorotrast bottle. ... Thorium dioxide (ThO2), also called thorium(IV) oxide (IUPAC) is a white, crystalline powder. ... Medical imaging designates the ensemble of techniques and processes used to create images of the human body (or parts thereof) for clinical purposes (medical procedures seeking to reveal, diagnose or examine disease) or medical science (including the study of normal anatomy and function). ... Jaundice, also known as icterus (attributive adjective: icteric), is a yellowing of the skin, conjunctiva (a clear covering over the sclera, or whites of the eyes) and mucous membranes caused by hyperbilirubinemia (increased levels of bilirubin in red blooded animals). ... Weight loss, in the context of medicine or health or physical fitness, is a reduction of the total body weight, 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. ... Pruritis is a misspelling of the medical condition pruritus. ... Blood tests are laboratory tests done on blood to gain an appreciation of disease states and the function of organs. ... Endoscopic images of a duodenal ulcer A flexible endoscope. ...


Surgery is the only potentially curative treatment, but most patients have advanced and inoperable disease at the time of diagnosis. After surgery, adjuvant chemotherapy or radiation therapy may be given to increase the chances of cure. Patients with advanced and inoperable cholangiocarcinoma are generally treated with chemotherapy and palliative care measures. Areas of ongoing medical research in cholangiocarcinoma include the use of newer targeted therapies (such as erlotinib) and the use of photodynamic therapy. In medicine, adjuvants are agents which modify the effect of other agents while having few if any direct effects when given by themselves. ... Chemotherapy is the use of chemical substances to treat disease. ... Varian Clinac 2100C Linear Accelerator Radiation therapy (or radiotherapy) is the medical use of ionizing radiation as part of cancer treatment to control malignant cells (not to be confused with radiology, the use of radiation in medical imaging and diagnosis). ... Palliative care (from Latin palliare, to cloak) is any form of medical care or treatment that concentrates on reducing the severity of disease symptoms, rather than providing a cure. ... Medical research (or experimental medicine) is basic research and applied research conducted to aid the body of knowledge in the field of medicine. ... Targeted cancer therapy is a type of chemotherapy which blocks the growth of cancer cells by interfering specific targeted molecules needed for carcinogenesis and tumor growth. ... Erlotinib hydrochloride (trade name Tarceva, Genentech/OSIP, originally coded as OSI-774) is a drug used to treat non-small cell lung cancer, pancreatic cancer and several other types of cancer. ... Shown is close up of surgeons hands in an operating room with a beam of light traveling along fiber optics for photodynamic therapy. ...

Contents

Symptoms

Yellowing of the skin and eyes (jaundice)

The most common symptom of cholangiocarcinoma is jaundice (yellowing of the eyes and skin), which occurs when bile ducts are blocked by the tumor. Other common symptoms include, in order of frequency: generalized itching (66%), abdominal pain (30%–50%), weight loss (30%–50%), and fever (up to 20%).[3] 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.[4] Image File history File links PHIL_2860_lores. ... Image File history File links PHIL_2860_lores. ... Jaundice, also known as icterus (attributive adjective: icteric), is a yellowing of the skin, conjunctiva (a clear covering over the sclera, or whites of the eyes) and mucous membranes caused by hyperbilirubinemia (increased levels of bilirubin in red blooded animals). ... Pruritis is a misspelling of the medical condition pruritus. ... Abdominal pain can be one of the symptoms associated with transient disorders or serious disease. ... Weight loss, in the context of medicine or health or physical fitness, is a reduction of the total body weight, 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. ... This article needs additional references or sources for verification. ...


Blood tests of liver function in patients with cholangiocarcinoma often reveal a so-called "obstructive picture", with elevated bilirubin, alkaline phosphatase, and gamma glutamyl transferase levels and relatively normal transaminase levels. Such laboratory findings suggest obstruction of the bile ducts, rather than inflammation or infection of the liver, as the primary cause of the jaundice.[5] Liver function tests (LFTs or LFs), which include liver enzymes, are groups of clinical biochemistry laboratory blood assays designed to give information about the state of a patients liver. ... Bilirubin is a yellow breakdown product of normal heme catabolism. ... Ball and stick model of alkaline phosphatase Alkaline phosphatase (ALP) (EC 3. ... Gamma glutamyl transferase (GGT or GGTP, or Gamma-GT) (EC 2. ... 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. ... An abscess on the skin, showing the redness and swelling characteristic of inflammation. ...


Epidemiology

Age-standardized mortality rates from intrahepatic (IC) and extrahepatic (EC) cholangiocarcinoma for men and women, by country. Source: Khan et al, 2002.[6]
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 of 1–2 cases per 100,000 people.[1] Autopsy series have reported a prevalence of 0.01% to 0.46%.[7] 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, a major risk factor, in men).[8] The prevalence of cholangiocarcinoma in patients with primary sclerosing cholangitis may be as high as 30%, based on autopsy studies.[9] Age Standardized Mortality Rates are used to compare the mortality rates of places without being skewed by the difference in age distributions from place to place. ... The incidence of disease is defined as the number of new cases of disease occurring in a population during a defined time interval. ... Post-mortem, postmortem and post mortem redirect here. ... In epidemiology, the prevalence of a disease in a statistical population is defined as the total number of cases of the disease 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. ... Primary sclerosing cholangitis (PSC) is a form of cholangitis due to an autoimmune reaction. ...


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, Europe, Asia, and Australia.[10] 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, has also been increasing during this time frame.[11] North America North America is a continent[1] in the Earths northern hemisphere and (chiefly) western hemisphere. ... For other uses, see Europe (disambiguation). ... For other uses, see Asia (disambiguation). ... Species Human immunodeficiency virus 1 Human immunodeficiency virus 2 Human immunodeficiency virus (HIV) is a retrovirus that causes acquired immunodeficiency syndrome (AIDS, a condition in humans in which the immune system begins to fail, leading to life-threatening opportunistic infections). ...


Risk factors

Life cycle of Clonorchis sinensis, a liver fluke associated with cholangiocarcinoma
Life cycle of Clonorchis sinensis, a liver fluke associated with cholangiocarcinoma

A number of risk factors for the development of cholangiocarcinoma have been described; in the Western world, the most common of these is primary sclerosing cholangitis (PSC), an inflammatory disease of the bile ducts which is in turn closely associated with ulcerative colitis (UC).[12] Epidemiologic studies have suggested that the lifetime risk of developing cholangiocarcinoma for a person with PSC is 10%–15%,[13] although autopsy series have found rates as high as 30% in this population.[9] The mechanism by which PSC increases the risk of cholangiocarcinoma is not well-understood. Image File history File links No higher resolution available. ... Image File history File links No higher resolution available. ... }} The Clonorchis sinensis is a human liver fluke in the class Trematoda, Phylum Platyhelminthes. ... Liver flukes are a polyphyletic group of a trematodes (a kind of flatworm). ... A risk factor is a variable associated with an increased risk of disease or infection but risk factors are not necessarily causal. ... Primary sclerosing cholangitis (PSC) is a form of cholangitis due to an autoimmune reaction. ... An abscess on the skin, showing the redness and swelling characteristic of inflammation. ...


Certain parasitic liver diseases may be risk factors as well. Colonization with the liver flukes Opisthorchis viverrini (found in Thailand, Laos, and Malaysia) or Clonorchis sinensis (found in Japan, Korea, and Vietnam) has been associated with the development of cholangiocarcinoma.[14][15][16] Patients with chronic liver disease, whether in the form of viral hepatitis (e.g. hepatitis B or C),[17][18][19] alcoholic liver disease, or cirrhosis from other causes, are at increased risk of cholangiocarcinoma.[11][20] HIV infection was also identified in one study as a potential risk factor for cholangiocarcinoma, although it was unclear whether HIV itself or correlated factors (e.g. hepatitis C infection) were responsible for the association.[11] A parasitic disease is a disease caused or transmitted by a parasite. ... Liver flukes are a polyphyletic group of a trematodes (a kind of flatworm). ... Opisthorchis viverrini - Wikipedia, the free encyclopedia /**/ @import /skins-1. ... }} The Clonorchis sinensis is a human liver fluke in the class Trematoda, Phylum Platyhelminthes. ... This article is about the Korean peninsula and civilization. ... “HBV” redirects here. ... This page is for the disease. ... Cirrhosis is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrotic scar tissue as well as regenerative nodules, leading to progressive loss of liver function. ... Species Human immunodeficiency virus 1 Human immunodeficiency virus 2 Human immunodeficiency virus (HIV) is a retrovirus that causes acquired immunodeficiency syndrome (AIDS, a condition in humans in which the immune system begins to fail, leading to life-threatening opportunistic infections). ...


Congenital liver abnormalities, such as Caroli's syndrome or choledochal cysts, have been associated with an approximately 15% lifetime risk of developing cholangiocarcinoma.[21][22] The rare inherited disorders Lynch syndrome II and biliary papillomatosis are associated with cholangiocarcinoma.[23][24] The presence of gallstones (cholelithiasis) is not clearly associated with cholangiocarcinoma. However, intrahepatic stones (so-called hepatolithiasis), which are rare in the West but common in parts of Asia, have been strongly associated with cholangiocarcinoma.[25][26][27] Exposure to Thorotrast, a form of thorium dioxide which was used as a radiologic contrast medium, 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.[28][29] A congenital disorder is any medical condition that is present at birth. ... Caroli disease is a rare congenital disease. ... Hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome, is characterized by an increased risk of colorectal cancer and other cancers such as endometrium, ovary, stomach, small intestine, hepatobiliary tract, upper urinary tract, brain, and skin. ... In medicine, gallstones are crystalline bodies formed within the body by accretion or concretion of normal or abnormal bile components. ... Thorotrast bottle. ... Thorium dioxide (ThO2), also called thorium(IV) oxide (IUPAC) is a white, crystalline powder. ... Radiocontrast agents (or simply contrast agents) are compounds used to improve the visibility of internal bodily structures in an X-ray image. ... In pathology, a carcinogen is any substance or agent that promotes cancer. ...


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 may be referred to eponymously as a Klatskin tumor.[30] Bile, which is synthesized in the liver, is carried to the right and left hepatic ducts, which converge to form the common hepatic duct. ... An eponym is the name of a person, whether real or fictitious, who has (or is thought to have) given rise to the name of a particular place, tribe, discovery, or other item. ... A Klatskin tumor is a cholangiocarcinoma (cancer of the biliary tree) occurring at the confluence of the right and left intrahepatic bile ducts. ...


The cell of origin of cholangiocarcinoma is unknown, although recent evidence has suggested that it may arise from a pluripotent hepatic stem cell.[31][32][33] Cholangiocarcinoma is thought to develop through a series of stages — from early hyperplasia and metaplasia, through dysplasia, to the development of frank carcinoma — in a process similar to that seen in the development of colon cancer.[34] Chronic inflammation and obstruction of the bile ducts, and the resulting impaired bile flow, are thought to play a role in this progression.[34][35][36] In cell biology, a pluripotent cell is one able to differentiate into many cell types. ... Stem cell division and differentiation. ... Hyperplasia (or hypergenesis) is a general term for an increase in the number of the cells of an organ or tissue causing it to increase in size. ... Metaplasia is the replacement of one differentiated cell type with another differentiated cell type. ... Dysplasia (from Greek, roughly: bad form) is a term used in pathology to refer to an abnormality in maturation of cells within a tissue. ... In medicine, carcinoma is any cancer that arises from epithelial cells. ... Diagram of the stomach, colon, and rectum Colorectal cancer includes cancerous growths in the colon, rectum and appendix. ... An abscess on the skin, showing the redness and swelling characteristic of inflammation. ...


Histologically, cholangiocarcinomas may vary from undifferentiated to well-differentiated. They are often surrounded by a brisk fibrotic or desmoplastic tissue response; in the presence of extensive fibrosis, it can be difficult to distinguish well-differentiated cholangiocarcinoma from normal reactive epithelium. There is no entirely specific immunohistochemical stain that can distinguish malignant from benign biliary ductal tissue, although staining for cytokeratins, carcinoembryonic antigen, and mucins may aid in diagnosis.[37] Most tumors (>90%) are adenocarcinomas.[38] A thin section of lung tissue stained with hematoxylin and eosin. ... Embryonic stem cells differentiate into cells in various body organs. ... Fibrosis is the formation or development of excess fibrous connective tissue in an organ or tissue as a reparative or reactive process, as opposed to a formation of fibrous tissue as a normal constituent of an organ or tissue. ... This article is being considered for deletion in accordance with Wikipedias deletion policy. ... This article is about the epithelium as it relates to animal anatomy. ... Immunohistochemistry or IHC refers to the process of localizing proteins in cells of a tissue section exploiting the principle of antibodies binding specifically to antigens in biological tissues. ... In medicine, malignant is a clinical term that means to be severe and become progressively worse, as in malignant hypertension. ... Look up Benign in Wiktionary, the free dictionary. ... Categories: Cell biology stubs | Keratins ... Carcinoembryonic antigen (CEA) is a glycoprotein involved in cell adhesion. ... Mucins are a family of large, heavily glycosylated proteins. ... Adenocarcinoma is a form of carcinoma that originates in glandular tissue. ...


Diagnosis

Cholangiocarcinoma is definitively diagnosed from tissue, i.e. it is proven by biopsy 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. Jaundice, also known as icterus (attributive adjective: icteric), is a yellowing of the skin, conjunctiva (a clear covering over the sclera, or whites of the eyes) and mucous membranes caused by hyperbilirubinemia (increased levels of bilirubin in red blooded animals). ...


Blood tests

There are no specific blood tests that can diagnose cholangiocarcinoma by themselves. Serum levels of carcinoembryonic antigen (CEA) and CA19-9 are often elevated, but are not sensitive or specific enough to be used as a general screening tool. However, they may be useful in conjunction with imaging methods in supporting a suspected diagnosis of cholangiocarcinoma.[39] Blood tests are laboratory tests done on blood to gain an appreciation of disease states and the function of organs. ... Carcinoembryonic antigen (CEA) is a glycoprotein involved in cell adhesion. ... The sensitivity of a binary classification test or algorithm, such as a blood test to determine if a person has a certain disease, or an automated system to detect faulty products in a factory, is a parameter that expresses something about the tests performance. ... The specificity is a statistical measure of how well a binary classification test correctly identifies the negative cases, or those cases that do not meet the condition under study. ... Screening, in medicine, is a strategy used to identify disease in an unsuspecting population. ... Medical imaging designates the ensemble of techniques and processes used to create images of the human body (or parts thereof) for clinical purposes (medical procedures seeking to reveal, diagnose or examine disease) or medical science (including the study of normal anatomy and function). ...


Abdominal imaging

CT scan showing cholangiocarcinoma

Ultrasound of the liver and biliary tree is often used as the initial imaging modality in patients with suspected obstructive jaundice.[40][41] Ultrasound can identify obstruction and ductal dilatation and, in some cases, may be sufficient to diagnose cholangiocarcinoma.[42] Computed tomography (CT) scanning may also play an important role in the diagnosis of cholangiocarcinoma.[43][44][45] Image File history File links Size of this preview: 800 × 534 pixelsFull resolution (886 × 591 pixel, file size: 51 KB, MIME type: image/jpeg) CT scan showing cholangiocarcinoma. ... Image File history File links Size of this preview: 800 × 534 pixelsFull resolution (886 × 591 pixel, file size: 51 KB, MIME type: image/jpeg) CT scan showing cholangiocarcinoma. ... negron305 Cat scan redirects here. ... For other uses, see Ultrasound (disambiguation). ... For the bird, see Liver bird. ... A bile duct is any of a number of long tube-like structures that carry bile. ... negron305 Cat scan redirects here. ...


Imaging of the biliary tree

ERCP image of cholangiocarcinoma, showing common bile duct stricture and dilation of the proximal common bile duct

While abdominal imaging can be useful in the diagnosis of cholangiocarcinoma, direct imaging of the bile ducts is often necessary. Endoscopic retrograde cholangiopancreatography (ERCP), an endoscopic 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 and to place stents or perform other interventions to relieve biliary obstruction.[5] Endoscopic ultrasound can also be performed at the time of ERCP and may increase the accuracy of the biopsy and yield information on lymph node invasion and operability.[46] As an alternative to ERCP, percutaneous transhepatic cholangiography (PTC) may be utilized. Magnetic resonance cholangiopancreatography (MRCP) is a non-invasive alternative to ERCP.[47][48][49] 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.[50][51][52] Image File history File links No higher resolution available. ... Image File history File links No higher resolution available. ... Endoscopic retrograde cholangiopancreatography (ERCP) is endoscopy of the biliary tree and the pancreatic duct. ... A bile duct is any of a number of long tube-like structures that carry bile. ... Duodenoscopic image of two pigment stones extracted from common bile duct after sphincterotomy Fluoroscopic image of common bile duct stone seen at the time of ERCP. The stone is impacted in the distal common bile duct. ... Endoscopic images of a duodenal ulcer A flexible endoscope. ... Gastroenterology or Gastrology might be better described as the field of digestive diseases, which are traditionally separated by anatomic or functional category. ... Brain biopsy A biopsy (in Greek: bios = life and opsy = look/appearance) is a medical test involving the removal of cells or tissues for examination. ... Endoscopic image of self-expanding metallic stent in esophagus, which was used to palliatively treat esophageal cancer. ... Endoscopic ultrasound is an ultrasound that is placed into the stomach and duodenum via the upper GI tract. ... Lymph nodes are components of the lymphatic system. ... Percutaneous transhepatic cholangiography (PTHC) is a diagnostic test used to visualize the anatomy of the biliary tract. ... MRCP is an imaging technique which detects biliary and pancreatic ducts in a non-invasive manner, moreover, after secretin stimulation, dynamic MRCP images of the pancreatic duct can be acquired. ... The term non-invasive in Medicine has two meanings: A medical procedure which does not penetrates or breaks the skin or a body cavity, i. ...


Surgery

Surgical exploration may be necessary to obtain a suitable biopsy and to accurately stage a patient with cholangiocarcinoma. Laparoscopy can be used for staging purposes and may avoid the need for a more invasive surgical procedure, such as laparotomy, in some patients.[53][54] Surgery is also the only curative option for cholangiocarcinoma, although it is limited to patients with early-stage disease (see below). “Surgeon” redirects here. ... Brain biopsy A biopsy (in Greek: bios = life and opsy = look/appearance) is a medical test involving the removal of cells or tissues for examination. ... The stage of a cancer is a descriptor (usually numbers I to IV) of how much the cancer has spread. ... Laparoscopic surgery, also called keyhole surgery (when natural body openings are not used), bandaid surgery, or minimally invasive surgery (MIS), is a surgical technique. ... A laparotomy is a surgical maneuver involving an incision through the abdominal wall to gain access into the abdominal cavity. ...


Pathology

Histologically, cholangiocarcinomas are classically well to moderately differentiated. Immunohistochemistry is useful in the diagnosis and can be used to differentiate a cholangiocarcinoma primary tumour from metastasis of most other gastrointestinal tumours.[55] Cytological scrappings are often non-diagnostic.[56] Immunohistochemistry or IHC refers to the process of localizing proteins in cells of a tissue section exploiting the principle of antibodies binding specifically to antigens in biological tissues. ...


Staging

Although there are at least 3 staging systems for cholangiocarcinoma (e.g. Bismuth, Blumgart, American Joint Committee on Cancer) none have been shown to be useful in predicting survival.[57] The most important staging issue is whether the tumor can be surgically removed, or whether it is too advanced or invasive for surgical treatment. Often, this determination can only be made at the time of surgery.[5] The stage of a cancer is a descriptor (usually numbers I to IV) of how much the cancer has spread. ... The American Joint Committee on Cancer (AJCC) is an organization best known for defining and popularizing cancer staging standards. ... Resection is a method of orientation (direction or position finding) using a compass and topographic map. ...


General guidelines for operability include:[58][59]

  • Absence of lymph node or liver metastases
  • Absence of involvement of the portal vein
  • Absence of direct invasion of adjacent organs
  • Absence of widespread metastatic disease

Lymph nodes are components of the lymphatic system. ... For the musical composition, see Metastasis (Xenakis composition). ... The portal vein is a major vein in the human body draining blood from the digestive system and its associated glands. ...

Prognosis

Surgical resection offers the only potential chance of cure in cholangiocarcinoma. 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) are generally treated 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 nodes.[60] Intrahepatic cholangiocarcinomas (those arising from the bile ducts within the liver) are usually treated with partial hepatectomy. 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.[61] 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 and potentially part of the liver. In patients with operable perihilar tumors, reported 5-year survival rates range from 20%–50%.[62] Bile, which is synthesized in the liver, is carried to the right and left hepatic ducts, which converge to form the common hepatic duct. ... It has been suggested that this article or section be merged into Pancreaticoduodenectomy. ... Prognosis (older Greek πρόγνωσις, modern Greek πρόγνωση - literally fore-knowing, foreseeing) is a medical term denoting the doctors prediction of how a patients disease will progress, and whether there is chance of recovery. ... Lymph nodes are components of the lymphatic system. ... For the bird, see Liver bird. ... Hepatectomy consists on the surgical resection of the liver. ... Laparoscopic Cholecystectomy as seen through laparoscope X-Ray during Laparoscopic Cholecystectomy Cholecystectomy (, plural: cholecystectomies,) is the surgical removal of the gallbladder. ...


The prognosis may be worse for patients with primary sclerosing cholangitis who develop cholangiocarcinoma, likely because the cancer is not detected until it is advanced.[9][63] Some evidence suggests that outcomes may be improving with more aggressive surgical approaches and adjuvant therapy.[64] Prognosis (older Greek πρόγνωσις, modern Greek πρόγνωση - literally fore-knowing, foreseeing) is a medical term denoting the doctors prediction of how a patients disease will progress, and whether there is chance of recovery. ... In medicine, adjuvants are agents which modify the effect of other agents while having few if any direct effects when given by themselves. ...


Treatment

Cholangiocarcinoma is considered curable only by surgical removal. Without surgery, it is a rapidly fatal disease with 5-year survival rates of less than 5%.[65] Often, the operability of the tumor can only be assessed at the time of surgery;[66] therefore, most patients undergo exploratory surgery unless there is a clear-cut indication that the tumor is inoperable.[5] Resection is a method of orientation (direction or position finding) using a compass and topographic map. ...


Adjuvant therapy followed by liver transplantation may have a role in treatment of certain unresectable cases.[67]


Adjuvant chemotherapy and radiation therapy

If the tumor can be removed surgically, patients may receive adjuvant chemotherapy or 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), adjuvant therapy is of uncertain benefit. Both positive[68][69] and negative[4][70][71] results have been reported with adjuvant radiation therapy in this setting, and no prospective randomized controlled trials have been conducted as of March 2007. Adjuvant chemotherapy appears to be ineffective in patients with completely resected tumors.[72] 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.[73] In medicine, adjuvants are agents which modify the effect of other agents while having few if any direct effects when given by themselves. ... Chemotherapy is the use of chemical substances to treat disease. ... Varian Clinac 2100C Linear Accelerator Radiation therapy (or radiotherapy) is the medical use of ionizing radiation as part of cancer treatment to control malignant cells (not to be confused with radiology, the use of radiation in medical imaging and diagnosis). ... Excision means to remove as if by cutting. It can be a euphemism for Female circumcision. ... A randomized controlled trial (RCT) is a form of clinical trial, or scientific procedure used in the testing of the efficacy of medicines or medical procedures. ...


Treatment of advanced disease

The majority of cases of cholangiocarcinoma present as unresectable disease.[74] If the tumor cannot be surgically removed, patients are often treated with palliative chemotherapy with or without radiotherapy. Chemotherapy has been shown in a randomized controlled trial to improve quality of life and extend survival in patients with inoperable cholangiocarcinoma.[75] There is no single chemotherapy regimen which is universally used, and enrollment in clinical trials is often recommended when possible.[73] Chemotherapy agents used to treat cholangiocarcinoma include 5-fluorouracil with leucovorin,[76] gemcitabine as a single agent,[77] or gemcitabine plus cisplatin,[78] irinotecan,[79] or capecitabine.[80] A small pilot study suggested possible benefit from the tyrosine kinase inhibitor erlotinib in patients with advanced cholangiocarcinoma.[81] Palliative care (from Latin palliare, to cloak) is any form of medical care or treatment that concentrates on reducing the severity of disease symptoms, rather than providing a cure. ... Chemotherapy is the use of chemical substances to treat disease. ... Radiation therapy (or radiotherapy) is the medical use of ionizing radiation as part of cancer treatment to control malignant cells (not to be confused with radiology, the use of radiation in medical imaging and diagnosis). ... A randomized controlled trial (RCT) is a form of clinical trial, or scientific procedure used in the testing of the efficacy of medicines or medical procedures. ... The well-being or quality of life of a population is an important concern in economics and political science. ... In health care, including medicine, a clinical trial (synonyms: clinical studies, research protocols, medical research) is a process in which a medicine or other medical treatment is tested for its safety and effectiveness, often in comparison to existing treatments. ... Fluorouracil (5-FU) is a drug that is used in the treatment of cancer. ... Folinic acid, generally administered as calcium folinate, is an adjuvant used in cancer chemotherapy involving the drug methotrexate. ... Gemcitabine is a nucleoside used as chemotherapy. ... Cisplatin, cisplatinum or cis-diamminedichloroplatinum(II) (CDDP) is a platinum-based chemotherapy drug used to treat various types of cancers, including sarcomas, some carcinomas (e. ... Irinotecan is a chemotherapy agent that is a topoisomerase 1 inhibitor. ... Capecitabine (INN) (IPA: ) is an orally-administered chemotherapeutic agent used in the treatment of metastatic breast and colorectal cancers. ... Tyrosine kinases are a subclass of protein kinase, see there for the principles of protein phosphorylation A tyrosine kinase (EC 2. ... Erlotinib hydrochloride (trade name Tarceva, Genentech/OSIP, originally coded as OSI-774) is a drug used to treat non-small cell lung cancer, pancreatic cancer and several other types of cancer. ...


Photodynamic therapy, an experimental approach in which patients are injected with a light-sensitizing agent and light is then applied endoscopically directly to the tumor, has shown promising results compared to supportive care in two small randomized controlled trials. However, its ultimate role in the management of cholangiocarcinoma is unclear at present.[82][83] Shown is close up of surgeons hands in an operating room with a beam of light traveling along fiber optics for photodynamic therapy. ... Endoscopic images of a duodenal ulcer A flexible endoscope. ... A randomized controlled trial (RCT) is a form of clinical trial, or scientific procedure used in the testing of the efficacy of medicines or medical procedures. ...


Notes

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  2. ^ Patel T. "Worldwide trends in mortality from biliary tract malignancies". BMC Cancer 2: 10. PMID 11991810. 
  3. ^ Nagorney D, Donohue J, Farnell M, Schleck C, Ilstrup D (1993). "Outcomes after curative resections of cholangiocarcinoma". Arch Surg 128 (8): 871–7; discussion 877-9. PMID 8393652. 
  4. ^ a b Nakeeb A, Pitt H, Sohn T, Coleman J, Abrams R, Piantadosi S, Hruban R, Lillemoe K, Yeo C, Cameron J (1996). "Cholangiocarcinoma. A spectrum of intrahepatic, perihilar, and distal tumors". Ann Surg 224 (4): 463–73; discussion 473-5. PMID 8857851. 
  5. ^ a b c d Feldman, pp. 1493–1496.
  6. ^ Khan S, Taylor-Robinson S, Toledano M, Beck A, Elliott P, Thomas H (2002). "Changing international trends in mortality rates for liver, biliary and pancreatic tumours". J Hepatol 37 (6): 806-13. PMID 12445422. 
  7. ^ Vauthey J, Blumgart L (1994). "Recent advances in the management of cholangiocarcinomas". Semin Liver Dis 14 (2): 109-14. PMID 8047893. 
  8. ^ Henson D, Albores-Saavedra J, Corle D (1992). "Carcinoma of the extrahepatic bile ducts. Histologic types, stage of disease, grade, and survival rates". Cancer 70 (6): 1498-501. PMID 1516001. 
  9. ^ a b c Rosen C, Nagorney D, Wiesner R, Coffey R, LaRusso N (1991). "Cholangiocarcinoma complicating primary sclerosing cholangitis". Ann Surg 213 (1): 21-5. PMID 1845927. 
  10. ^ Multiple independent studies have documented a steady increase in the worldwide incidence of cholangiocarcinoma. Some relevant journal articles include:
    • Patel T. "Worldwide trends in mortality from biliary tract malignancies". BMC Cancer 2: 10. PMID 11991810. 
    • Patel T (2001). "Increasing incidence and mortality of primary intrahepatic cholangiocarcinoma in the United States". Hepatology 33 (6): 1353–7. PMID 11391522. 
    • Shaib Y, Davila J, McGlynn K, El-Serag H (2004). "Rising incidence of intrahepatic cholangiocarcinoma in the United States: a true increase?". J Hepatol 40 (3): 472-7. PMID 15123362. 
    • West J, Wood H, Logan R, Quinn M, Aithal G (2006). "Trends in the incidence of primary liver and biliary tract cancers in England and Wales 1971–2001". Br J Cancer 94 (11): 1751–8. PMID 16736026. 
    • Khan S, Taylor-Robinson S, Toledano M, Beck A, Elliott P, Thomas H (2002). "Changing international trends in mortality rates for liver, biliary and pancreatic tumours". J Hepatol 37 (6): 806-13. PMID 12445422. 
    • Welzel T, McGlynn K, Hsing A, O'Brien T, Pfeiffer R (2006). "Impact of classification of hilar cholangiocarcinomas (Klatskin tumors) on the incidence of intra- and extrahepatic cholangiocarcinoma in the United States". J Natl Cancer Inst 98 (12): 873-5. PMID 16788161. 
  11. ^ a b c Shaib Y, El-Serag H, Davila J, Morgan R, McGlynn K (2005). "Risk factors of intrahepatic cholangiocarcinoma in the United States: a case-control study". Gastroenterology 128 (3): 620-6. PMID 15765398. 
  12. ^ Chapman R. "Risk factors for biliary tract carcinogenesis". Ann Oncol 10 Suppl 4: 308-11. PMID 10436847. 
  13. ^ Epidemiologic studies which have addressed the incidence of cholangiocarcinoma in people with primary sclerosing cholangitis include the following:
    • Bergquist A, Ekbom A, Olsson R, Kornfeldt D, Lööf L, Danielsson A, Hultcrantz R, Lindgren S, Prytz H, Sandberg-Gertzén H, Almer S, Granath F, Broomé U (2002). "Hepatic and extrahepatic malignancies in primary sclerosing cholangitis". J Hepatol 36 (3): 321-7. PMID 11867174. 
    • Bergquist A, Glaumann H, Persson B, Broomé U (1998). "Risk factors and clinical presentation of hepatobiliary carcinoma in patients with primary sclerosing cholangitis: a case-control study". Hepatology 27 (2): 311-6. PMID 9462625. 
    • Burak K, Angulo P, Pasha T, Egan K, Petz J, Lindor K (2004). "Incidence and risk factors for cholangiocarcinoma in primary sclerosing cholangitis". Am J Gastroenterol 99 (3): 523-6. PMID 15056096. 
  14. ^ Watanapa P (1996). "Cholangiocarcinoma in patients with opisthorchiasis". Br J Surg 83 (8): 1062–64. PMID 8869303. 
  15. ^ Watanapa P, Watanapa W (2002). "Liver fluke-associated cholangiocarcinoma". Br J Surg 89 (8): 962-70. PMID 12153620. 
  16. ^ Shin H, Lee C, Park H, Seol S, Chung J, Choi H, Ahn Y, Shigemastu T (1996). "Hepatitis B and C virus, Clonorchis sinensis for the risk of liver cancer: a case-control study in Pusan, Korea". Int J Epidemiol 25 (5): 933-40. PMID 8921477. 
  17. ^ Kobayashi M, Ikeda K, Saitoh S, Suzuki F, Tsubota A, Suzuki Y, Arase Y, Murashima N, Chayama K, Kumada H (2000). "Incidence of primary cholangiocellular carcinoma of the liver in Japanese patients with hepatitis C virus-related cirrhosis". Cancer 88 (11): 2471–7. PMID 10861422. 
  18. ^ Yamamoto S, Kubo S, Hai S, Uenishi T, Yamamoto T, Shuto T, Takemura S, Tanaka H, Yamazaki O, Hirohashi K, Tanaka T (2004). "Hepatitis C virus infection as a likely etiology of intrahepatic cholangiocarcinoma". Cancer Sci 95 (7): 592-5. PMID 15245596. 
  19. ^ Lu H, Ye M, Thung S, Dash S, Gerber M (2000). "Detection of hepatitis C virus RNA sequences in cholangiocarcinomas in Chinese and American patients". Chin Med J (Engl) 113 (12): 1138–41. PMID 11776153. 
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  23. ^ Mecklin J, Järvinen H, Virolainen M (1992). "The association between cholangiocarcinoma and hereditary nonpolyposis colorectal carcinoma". Cancer 69 (5): 1112–4. PMID 1310886. 
  24. ^ Lee S, Kim M, Lee S, Jang S, Song M, Kim K, Kim H, Seo D, Song D, Yu E, Lee S, Min Y (2004). "Clinicopathologic review of 58 patients with biliary papillomatosis". Cancer 100 (4): 783-93. PMID 14770435. 
  25. ^ Lee C, Wu C, Chen G (2002). "What is the impact of coexistence of hepatolithiasis on cholangiocarcinoma?". J Gastroenterol Hepatol 17 (9): 1015–20. PMID 12167124. 
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  28. ^ Sahani D, Prasad S, Tannabe K, Hahn P, Mueller P, Saini S. "Thorotrast-induced cholangiocarcinoma: case report". Abdom Imaging 28 (1): 72-4. PMID 12483389. 
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  31. ^ Roskams T (2006). "Liver stem cells and their implication in hepatocellular and cholangiocarcinoma". Oncogene 25 (27): 3818–22. PMID 16799623. 
  32. ^ Liu C, Wang J, Ou Q (2004). "Possible stem cell origin of human cholangiocarcinoma". World J Gastroenterol 10 (22): 3374–6. PMID 15484322. 
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  35. ^ Holzinger F, Z'graggen K, Büchler M. "Mechanisms of biliary carcinogenesis: a pathogenetic multi-stage cascade towards cholangiocarcinoma". Ann Oncol 10 Suppl 4: 122-6. PMID 10436802. 
  36. ^ Gores G (2003). "Cholangiocarcinoma: current concepts and insights". Hepatology 37 (5): 961-9. PMID 12717374. 
  37. ^ de Groen P, Gores G, LaRusso N, Gunderson L, Nagorney D (1999). "Biliary tract cancers". N Engl J Med 341 (18): 1368–78. PMID 10536130. 
  38. ^ Henson D, Albores-Saavedra J, Corle D (1992). "Carcinoma of the extrahepatic bile ducts. Histologic types, stage of disease, grade, and survival rates". Cancer 70 (6): 1498-501. PMID 1516001. 
  39. ^ Studies of the performance of serum markers for cholangiocarcinoma (such as carcinoembryonic antigen and CA19-9) in patients with and without primary sclerosing cholangitis include the following:
    • Nehls O, Gregor M, Klump B (2004). "Serum and bile markers for cholangiocarcinoma". Semin Liver Dis 24 (2): 139-54. PMID 15192787. 
    • Siqueira E, Schoen R, Silverman W, Martin J, Rabinovitz M, Weissfeld J, Abu-Elmaagd K, Madariaga J, Slivka A, Martini J (2002). "Detecting cholangiocarcinoma in patients with primary sclerosing cholangitis". Gastrointest Endosc 56 (1): 40-7. PMID 12085033. 
    • Levy C, Lymp J, Angulo P, Gores G, Larusso N, Lindor K (2005). "The value of serum CA 19-9 in predicting cholangiocarcinomas in patients with primary sclerosing cholangitis". Dig Dis Sci 50 (9): 1734–40. PMID 16133981. 
    • Patel A, Harnois D, Klee G, LaRusso N, Gores G (2000). "The utility of CA 19-9 in the diagnoses of cholangiocarcinoma in patients without primary sclerosing cholangitis". Am J Gastroenterol 95 (1): 204-7. PMID 10638584. 
  40. ^ Saini S (1997). "Imaging of the hepatobiliary tract". N Engl J Med 336 (26): 1889–94. PMID 9197218. 
  41. ^ Sharma M, Ahuja V. "Aetiological spectrum of obstructive jaundice and diagnostic ability of ultrasonography: a clinician's perspective". Trop Gastroenterol 20 (4): 167-9. PMID 10769604. 
  42. ^ Bloom C, Langer B, Wilson S. "Role of US in the detection, characterization, and staging of cholangiocarcinoma". Radiographics 19 (5): 1199-218. PMID 10489176. 
  43. ^ Valls C, Gumà A, Puig I, Sanchez A, Andía E, Serrano T, Figueras J. "Intrahepatic peripheral cholangiocarcinoma: CT evaluation". Abdom Imaging 25 (5): 490-6. PMID 10931983. 
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  45. ^ Zhang Y, Uchida M, Abe T, Nishimura H, Hayabuchi N, Nakashima Y. "Intrahepatic peripheral cholangiocarcinoma: comparison of dynamic CT and dynamic MRI". J Comput Assist Tomogr 23 (5): 670-7. PMID 10524843. 
  46. ^ Sugiyama M, Hagi H, Atomi Y, Saito M. "Diagnosis of portal venous invasion by pancreatobiliary carcinoma: value of endoscopic ultrasonography". Abdom Imaging 22 (4): 434-8. PMID 9157867. 
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  59. ^ Rajagopalan V, Daines W, Grossbard M, Kozuch P (2004). "Gallbladder and biliary tract carcinoma: A comprehensive update, Part 1". Oncology (Williston Park) 18 (7): 889-96. PMID 15255172. 
  60. ^ Studies of surgical outcomes in distal cholangiocarcinoma include:
    • Nakeeb A, Pitt H, Sohn T, Coleman J, Abrams R, Piantadosi S, Hruban R, Lillemoe K, Yeo C, Cameron J (1996). "Cholangiocarcinoma. A spectrum of intrahepatic, perihilar, and distal tumors". Ann Surg 224 (4): 463–73; discussion 473-5. PMID 8857851. 
    • Nagorney D, Donohue J, Farnell M, Schleck C, Ilstrup D (1993). "Outcomes after curative resections of cholangiocarcinoma". Arch Surg 128 (8): 871–7; discussion 877-9. PMID 8393652. 
    • Jang J, Kim S, Park D, Ahn Y, Yoon Y, Choi M, Suh K, Lee K, Park Y (2005). "Actual long-term outcome of extrahepatic bile duct cancer after surgical resection". Ann Surg 241 (1): 77–84. PMID 15621994. 
    • Bortolasi L, Burgart L, Tsiotos G, Luque-De León E, Sarr M (2000). "Adenocarcinoma of the distal bile duct. A clinicopathologic outcome analysis after curative resection". Dig Surg 17 (1): 36–41. PMID 10720830. 
    • Fong Y, Blumgart L, Lin E, Fortner J, Brennan M (1996). "Outcome of treatment for distal bile duct cancer". Br J Surg 83 (12): 1712–5. PMID 9038548. 
  61. ^ Studies of outcome in intrahepatic cholangiocarcinoma include:
    • Nakeeb A, Pitt H, Sohn T, Coleman J, Abrams R, Piantadosi S, Hruban R, Lillemoe K, Yeo C, Cameron J (1996). "Cholangiocarcinoma. A spectrum of intrahepatic, perihilar, and distal tumors". Ann Surg 224 (4): 463–73; discussion 473-5. PMID 8857851. 
    • Lieser M, Barry M, Rowland C, Ilstrup D, Nagorney D (1998). "Surgical management of intrahepatic cholangiocarcinoma: a 31-year experience". J Hepatobiliary Pancreat Surg 5 (1): 41-7. PMID 9683753. 
    • Valverde A, Bonhomme N, Farges O, Sauvanet A, Flejou J, Belghiti J (1999). "Resection of intrahepatic cholangiocarcinoma: a Western experience". J Hepatobiliary Pancreat Surg 6 (2): 122-7. PMID 10398898. 
    • Nakagohri T, Asano T, Kinoshita H, Kenmochi T, Urashima T, Miura F, Ochiai T (2003). "Aggressive surgical resection for hilar-invasive and peripheral intrahepatic cholangiocarcinoma". World J Surg 27 (3): 289-93. PMID 12607053. 
    • Weber S, Jarnagin W, Klimstra D, DeMatteo R, Fong Y, Blumgart L (2001). "Intrahepatic cholangiocarcinoma: resectability, recurrence pattern, and outcomes". J Am Coll Surg 193 (4): 384-91. PMID 11584966. 
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References

  • Feldman: Sleisenger & Fordtran's Gastrointestinal and Liver Disease. 8th ed., copyright © 2006 Saunders, An Imprint of Elsevier. ISBN 1416002456

External links


 
 

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