Overview of the affected part

The gall bladder and the bile duct are part of the digestive system. Together, the esophagus, stomach, large and small intestine, aided by the liver, gallbladder and pancreas convert the nutritive components of food into energy and break down the non-nutritive components into waste to be excreted.

Anatomy and Physiology of the Gallbladder and Bile Ducts

The anatomy of the biliary tree is a little complicated, but it is important to understand. The liver's cells (hepatocytes) excrete bile into canaliculi, which are intercellular spaces between the liver cells. These drain into the right and left hepatic ducts, after which bile travels via the common hepatic and cystic ducts to the gallbladder. The gallbladder, which has a capacity of 50 milliliters (about 5 tablespoons), concentrates the bile 10 fold by removing water and stores it until a person eats. At this time, bile is discharged from the gallbladder via the cystic duct into the common bile duct and then into the duodenum (the first part of the small intestine), where it begins to dissolve the fat in ingested food. The liver excretes approximately 500 to 1000 milliliters (50 to 100 tablespoons) of bile each day. Most (95%) of the bile that has entered the intestines is resorbed in the last part of the small intestine (known as the terminal ileum), and returned to the liver for reuse.

The many functions of bile are best understood by knowing the composition of bile: 1. Bile Salts (cholates, chenodeoxycholate, deoxycholate): these are produced by the liver's breakdown of cholesterol. They function in bile as detergents that dissolve dietary fat and allow it to be absorbed. Hence, disruption of bile excretion disrupts the normal absorption of fat, a process called malabsorption. Patients develop diarrhea because the fat is not absorbed (steatorrhea) , and develop deficiencies of the fat-soluble vitamins (A, D, E, and K). 2. Cholesterol and phospholipids-while only 4% of bile is cholesterol, the secretion of cholesterol and its metabolites (bile salts) into bile is the body's major route of elimination of cholesterol. Phospholipids, which are components of cell membranes, enhance the cholesterol solubilizing properties of bile salts. Inefficient excretion of cholesterol can cause an increased serum cholesterol. This predisposes to vascular disease (heart attacks, strokes, etc.) 3. Bilirubin-while this comprises only 0.3% of bile, it is responsible for bile's yellow color. Bilirubin is a product of the body's metabolism of hemoglobin, the carrier of oxygen in red blood cells. Disruption of the excretion of this component of bile leads to a yellow discoloration of the eyes and skin (jaundice). 4. Protein and miscellaneous components Bile production and recirculation is the main excretory function of the liver. Tumors that obstruct the flow of bile from the liver can also impair other liver functions. Therefore, it is necessary to understand these other functions to understand the symptoms that these tumors can cause. These include: Metabolic functions, such as the maintenance of glucose (blood sugar) levels Synthetic functions, such as the synthesis of serum proteins such as albumin, blood clotting (coagulation) factors, and complement (a mediator of inflammatory responses) Storage functions, such as the storage of sugar (glycogen), fat (triglycerides), iron, copper, and fat soluble vitamins (A, D, E, and K) Catabolic functions, such as the detoxification of drugs The biliary system is comprised of the organs and duct system that create, transport, store and release bile into the duodenum for digestion. Includes the liver, gallbladder and bile ducts (named the cystic, hepatic, common, and pancreatic duct).

the bile duct, which is a 4-inch to 5-inch tube that connects the liver and gallbladder to the small intestine. Within the liver, smaller tubes, similar to capillaries, drain bile from the cells in the liver into larger and larger branches, ending in a tube called the common bile duct. The bile duct allows bile, which is made in the liver and stored in the gallbladder, to flow into the small intestine. Bile is a liquid that helps to both break down fats found in foods and helps the body get rid of waste material filtered out of the bloodstream by the liver. http://www.youtube.com/attribution_link?u=%2Fwatch%3Fv%3D8YlPSOkwIRQ%26feature%3 Dshare&a=rK00QKZ11NS18Yzoq3EWOw VIDEO OF NORMAL BILE FLOW OVERVIEW ON CANCER The body is made up of trillions of living cells. Normal body cells grow, divide into new cells, and die in an orderly way. During the early years of a person's life, normal cells divide faster to allow the person to grow. After the person becomes an adult, most cells divide only to replace worn-out or dying cells or to repair injuries. Cancer begins when cells in a part of the body start to grow out of control. There are many kinds of cancer, but they all start because of out-ofcontrol growth of abnormal cells. Cancer cell growth is different from normal cell growth. Instead of dying, cancer cells continue to grow and form new, abnormal cells. Cancer cells can also invade (grow into) other tissues, something that normal cells cannot do. Growing out of control and invading other tissues are what makes a cell a cancer cell. Cells become cancer cells because of damage to DNA. DNA is in every cell and directs all its actions. In a normal cell, when DNA gets damaged the cell either repairs the damage or the cell dies. In cancer cells, the damaged DNA is not repaired, but the cell doesnt die like it should. Instead, this cell goes on making new cells that the body does not need. These new cells will all have the same damaged DNA as the first cell does.

People can inherit damaged DNA, but most DNA damage is caused by mistakes that happen while the normal cell is reproducing or by something in our environment. Sometimes the cause of the DNA damage is something obvious, like cigarette smoking. But often no clear cause is found. In most cases the cancer cells form a tumor. Some cancers, like leukemia, rarely form tumors. Instead, these cancer cells involve the blood and blood-forming organs and circulate through other tissues where they grow. Cancer cells often travel to other parts of the body, where they begin to grow and form new tumors that replace normal tissue. This process is called metastasis. It happens when the cancer cells get into the bloodstream or lymph vessels of our body. No matter where a cancer may spread, it is always named for the place where it started. For example, breast cancer that has pread to the liver is still called breast cancer, not liver cancer. Likewise, prostate cancer that has spread to the bone is metastatic prostate cancer, not bone cancer. Different types of cancer can behave very differently. For example, lung cancer and breast cancer are very different diseases. They grow at different rates and respond to different treatments. That is why people with cancer need treatment that is aimed at their particular kind of cancer. Not all tumors are cancerous. Tumors that arent cancer are called benign. Benign tumors can cause problems they can grow very large and press on healthy organs and tissues. But they cannot grow into (invade) other tissues. Because they cant invade, they also cant spread to other parts of the body (metastasize). These tumors are almost never life threatening.

http://www.youtube.com/attribution_link?a=ZRsFZZefSGR43q1XWq2rNw&u=%2Fwatch%3F v%3D8LhQllh46yI%26feature%3Dshare

video of a from a healthy cell to cancer cell

Cholangiocarcinoma is a medical term denoting a form of cancer that is composed of mutated epithelial cells (or cells showing characteristics of epithelial differentiation) that originate in the bile ducts which drain bile from the liver into the small intestine. Other biliary tract cancers include pancreatic cancer, gallbladder cancer, and cancer of the ampulla of Vater. Cholangiocarcinomas (CCCs) are malignancies of the biliary duct system that may originate in the liver and extrahepatic bile ducts, which terminate at the ampulla of Vater CCCs are encountered in 3 geographic regions: intrahepatic, extrahepatic (ie, perihilar), and distal extrahepatic. Perihilar tumors are the most common CCCs, and intrahepatic tumors are the least common. Perihilar tumors, also called Klatskin tumors (after Klatskin's description of them in 1965), occur at the bifurcation of right and left hepatic ducts. Distal extrahepatic tumors are located from the upper border of the pancreas to the ampulla. More than 95% of these tumors are ductal adenocarcinomas; many patients present with unresectable or metastatic disease. Cholangiocarcinoma is a relatively rare neoplasm that is classified as an adenocarcinoma (a cancer that forms glands or secretes significant amounts of mucins). It has an annual incidence rate of 12 cases per 100,000 in the Western world, but rates of cholangiocarcinoma have been rising worldwide over the past several decades.

Cancer can occur in any part of the bile duct. The part of the tube that is outside of the liver is called extrahepatic. It is in this portion of the bile duct where cancer usually arises. A perihilar cancer, also called a Klatskin tumor, begins where many small channels join into the bile duct at the point where it leaves the liver. About two-thirds of all cholangiocarcinomas occur here. Distal cholangiocarcinoma occurs at the opposite end of the duct from perihilar cancer, near where the bile duct empties into the small intestine. About one-fourth of all cholangiocarcinomas are distal cholangiocarcinomas. About 5% to 10% of cholangiocarcinomas are intrahepatic, or inside the liver. Adenocarcinoma is the most common type of extrahepatic cholangiocarcinoma, and accounting for up to 95% of all cholangiocarcinomas. Adenocarcinoma is cancer arising from the mucus glands lining the inside of the bile duct. Cholangiocarcinoma is another term that may be used to describe this type of cancer.

Pathophysiology
Cholangiocarcinoma is a tumor that arises from the intrahepatic or extrahepatic biliary epithelium. More than 90% are adenocarcinomas, and the remainder are squamous cell tumors. The etiology of most bile duct cancers remains undetermined. Long-standing inflammation, as with primary sclerosing cholangitis (PSC) or chronic parasitic infection, has been suggested to play a role by inducing hyperplasia, cellular proliferation, and, ultimately, malignant transformation. Intrahepatic cholangiocarcinoma may be associated with chronic ulcerative colitis and chronic cholecystitis. Cholangiocarcinomas tend to grow slowly and to infiltrate the walls of the ducts, dissecting along tissue planes. Local extension occurs into the liver, porta hepatis, and regional lymph nodes of the celiac and pancreaticoduodenal chains. Life-threatening infection (cholangitis) may occur that requires immediate antibiotic intervention and aggressive biliary drainage.

These tumors can be slow-growing tumors that spread locally via the lymphatic system, as well as involve local structures such as the blood vessels feeding the liver. Causes Cancerous tumors of the bile ducts are usually slow-growing and do not spread (metastasize) quickly. However, many of these tumors are already advanced by the time they are found. A cholangiocarcinoma may start anywhere along the bile ducts. These tumors block off the bile ducts. They affect both men and women. Most patients are older than 65. Risks for this condition include: Bile duct (choledochal) cysts Chronic biliary and liver inflammation History of infection with the parasitic worm, liver flukes Primary sclerosing cholangitis Ulcerative colitis

The etiology of most bile duct cancers remains undetermined. Currently, gallstones are not believed to increase the risk of cholangiocarcinoma. Chronic viral hepatitis and cirrhosis also do not appear to be risk factors.

Infections o In Southeast Asia, chronic infections with liver flukes, Clonorchis sinensis, and Opisthorchis viverrini have been causally related to cholangiocarcinoma. o Other parasites, such as Ascaris lumbricoides, have been implicated in the pathogenesis of cholangiocarcinoma. o Observations have raised the possibility that bacterial infections with Helicobacter species may play an etiologic role in biliary cancer.[9] Inflammatory bowel disease o A strong relationship exists between cholangiocarcinoma and primary sclerosing cholangitis. Cholangiocarcinoma generally develops in patients with longstanding ulcerative colitis and primary sclerosing cholangitis.[10] o The lifetime risk of developing this cancer in the setting of primary sclerosing cholangitis is 10-20%. At increased risk are patients with ulcerative colitis without symptomatic primary sclerosing cholangitis and a small subset of patients with Crohn disease. Chemical exposures o Certain chemical exposures have been implicated in the development of bile duct cancers, primarily in workers in the aircraft, rubber, and wood-finishing industries. o Cholangiocarcinoma occasionally has developed years after administration of the radiopaque medium thorium dioxide (ie, thorotrast). Congenital diseases of the biliary tree, including choledochal cysts and Caroli disease, have been associated with cholangiocarcinoma. Other conditions rarely associated with cholangiocarcinoma include bile duct adenomas, biliary papillomatosis, and alpha 1 -antitrypsin deficiency.

Symptoms

Chills Clay-colored stools Fever Itching Loss of appetite Pain in the upper right abdomen that may radiate to the back Weight loss Yellowing of the skin (jaundice)

Symptoms of Gallbladder and Bile Duct Cancer

Patients with bile duct cancer most often become symptomatic when the cancer obstructs (blocks) the drainage of bile. Because bile cannot be excreted into the bowel, the bilirubin pigments accumulate in the blood, causing jaundice (yellowing of the skin and the whites of the eyes) in 90% of patients. The jaundice is usually associated with itching of the skin (also called "pruritus"). The body compensates partially and excretes some of this bilirubin via the urine, so patients may have dark (cola colored) urine. Because bile cannot reach the intestine, the patient's stools become white (clay colored).

Other symptoms result from inflammation secondary to tumor obstruction. Patients with gallbladder cancer may have pain in the right upper portion of the abdomen. This pain is a result of inflammation of the gallbladder (cholecystitis) due to blockage of the cystic duct. In fact, approximately 1% of patients who undergo cholecystectomy (surgical removal of the gallbladder) for suspected cholecystitis prove to have unsuspected gallbladder carcinoma. Distal bile duct tumors near the ampulla of Vater, the point at which the bile drains into the bowel, obstruct the pancreatic duct and lead to inflammation of the pancreas (pancreatitis).

Symptoms of cholangiocarcinoma include jaundice, clay-colored stools, bilirubinuria (dark urine), pruritus, weight loss, and abdominal pain. Jaundice is the most common manifestation of bile duct cancer and, in general, is best detected in direct sunlight. The obstruction and subsequent cholestasis tend to occur early if the tumor is located in the common bile duct or common hepatic duct. Jaundice often occurs later in perihilar or intrahepatic tumors and is often a marker of advanced disease. The excess of conjugated bilirubin is associated with bilirubinuria and acholic stools. Pruritus usually is preceded by jaundice, but itching may be the initial symptom of cholangiocarcinoma. Pruritus may be related to circulating bile acids. Weight loss is a variable finding and may be present in one third of patients at the time of diagnosis. Abdominal pain is relatively common in advanced disease and often is described as a dull ache in the right upper quadrant. Statistics Primary cholangiocarcinoma is a rare disease. It is estimated that more than 2,500 new cases are diagnosed each year in the United States. However, the incidence of cholangiocarcinoma is increasing, mostly due to rising rates of intrahepatic cholangiocarcinoma that occurs in the liver. The reason for this increase is not known. It may be due to doctors having better tests to diagnose this type of cancer more accurately. Previously, they may have been thought to be a different sort of cancer. In some parts of the world, a parasite called liver flukes can infect the bile duct and cause cancer to form. Liver flukes are very common in Asia and the Middle East, and therefore cholangiocarcinoma is more common in these regions. Gall stones and inflammatory conditions of the gastrointestinal (GI) tract, such as ulcerative colitis or an associated condition called sclerosing cholangitis, increase the risk of cholangiocarcinoma. The five-year relative survival rate (the percentage of patients who survive at least five years after the cancer is detected, excluding those who die from other diseases) for people diagnosed with early-stage cholangiocarcinoma is about 30%. However, only about 20% of cholangiocarcinoma is found at an early stage. The five-year relative survival rate decreases if cancer has spread at the time of diagnosis. Cancer survival statistics should be interpreted with caution. These estimates are based on data from thousands of cases of this type of cancer in the United States and may not apply to a single

person. It is not possible to tell a person how long he or she will live with cholangiocarcinoma. Because the survival statistics are measured in five-year (or sometimes one-year) intervals, they may not represent advances made in the treatment or diagnosis of this cancer.

Epidemiology
Cholangiocarcinoma is an adenocarcinoma of the biliary tract,[85] along with pancreatic cancer (which occurs about 20 times more frequently),[86] 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. IC EC Country Cholangiocarcinoma is a relatively rare form of (men/women) (men/women) cancer; each year, approximately 2,000 to 0.60 / 0.43 0.70 / 0.87 U.S.A. 3,000 new cases are diagnosed in the United 0.23 / 0.10 5.87 / 5.20 Japan States, translating into an annual incidence of 0.70 / 0.53 0.90 / 1.23 Australia 12 cases per 100,000 people.[1] Autopsy series 0.43 / 0.60 England/Wales 0.83 / 0.63 have reported a prevalence of 0.01% to [88][89] 1.17 / 1.00 0.60 / 0.73 Scotland 0.46%. There is a higher prevalence of cholangiocarcinoma in Asia, which has been 0.27 / 0.20 1.20 / 1.37 France attributed to endemic chronic parasitic 0.13 / 0.13 2.10 / 2.60 Italy infestation. The incidence of Age-standardized mortality rates from cholangiocarcinoma increases with age, and intrahepatic (IC) and extrahepatic (EC) the disease is slightly more common in men cholangiocarcinoma for men and women, by than in women (possibly due to the higher rate country. Source: Khan et al., 2002.[87] of primary sclerosing cholangitis, a major risk factor, in men).[38] The prevalence of cholangiocarcinoma in patients with primary sclerosing cholangitis may be as high as 30%, based on autopsy studies.[12] 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.[90] 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.[19]

Epidemiology
Frequency

United States Each year, approximately 2500 cases of CCC occur, compared to 5000 cases of gallbladder cancer and 15,000 cases of hepatocellular cancer. Average incidence is 1 case per 100,000 persons per year. A study by Singal et al found that the frequency of intrahepatic cholangiocarcinoma has increased over time and is most commonly noted in females older than 60 years.[7] International Incidence in most Western countries ranges from 2 to 6 cases per 100,000 people per year. The highest annual incidences are in Japan, at 5.5 cases per 100,000 people, and in Israel, at 7.3 cases per 100,000 people.

Mortality/Morbidity
Despite aggressive anticancer therapy and interventional supportive care (ie, wall stents or percutaneous biliary drainage), median survival rate is low, since most patients (90%) are not eligible for curative resection. The overall survival is approximately 6 months.

Race
Native Americans have the highest annual incidence in North America, at 6.5 cases per 100,000 people. This rate is about 6 times higher than that in non Native American populations. The high prevalence of cholangiocarcinoma in people of Asian descent is attributable to endemic chronic parasitic infestation.

Sex
The male-to-female ratio for cholangiocarcinoma is 1:2.5 in patients in their 60s and 70s and 1:15 in patients younger than 40 years. According to the American Cancer Society, the number of new cases of liver and intrahepatic bile duct cancer in 2007 is estimated to be 13,650 for men and 5,510 for women, with estimated mortality of 11,280 and 5,500, respectively. The estimated number of new cases of gallbladder and other biliary cancers (extrahepatic cholangiocarcinoma) are 4,380 for men and 4,870 for women, with estimated mortality rates of 1,260 and 1,990, respectively.[8]

Age
Highest prevalence rate occurs in males and females in their 60s and 70s.

Staging

Staging is a way of describing a cancer, such as where it is located, if or where it has spread, and if it is affecting the functions of other organs in the body. Doctors use diagnostic tests to determine the cancer's stage, so staging may not be complete until all the tests are finished. Knowing the stage helps the doctor to decide what kind of treatment is best and can help predict a patient's prognosis (chance of recovery). There are different stage descriptions for different types of cancer. One tool that doctors use to describe the stage is the TNM system. This system uses three criteria to judge the stage of the cancer: the tumor itself, the lymph nodes around the tumor, and if the tumor has spread to the rest of the body. The results are combined to determine the stage of cancer for each person. There are five stages: stage 0 (zero) and stages I through IV (one through four). The stage provides a common way of describing the cancer so doctors can work together to plan the best treatments. TNM is an abbreviation for tumor (T), node (N), and metastasis (M). Doctors look at these three factors to determine the stage of cancer:

How large is the primary tumor and where is it located? (Tumor, T) Has the tumor spread to the lymph nodes? (Node, N) Has the cancer metastasized (spread) to other parts of the body? (Metastasis, M)

Intrahepatic cholangiocarcinoma (cancer that occurs in the bile duct within the liver) is staged using the same system as liver cancer. The staging of both intrahepatic and extrahepatic cholangiocarcinoma is below.

Intrahepatic cholangiocarcinoma staging Tumor. Using the TNM system, the "T" plus a letter or number (0 to 4) is used to describe the stage of intrahepatic cholangiocarcinoma. If there is more than one tumor, the lowercase letter "m" (multiple) is added to the "T" category. Specific tumor stage information is listed below: TX: The primary tumor cannot be assessed. T0: There is no evidence of a primary tumor. T1: The tumor is only a single tumor. It does not involve adjacent blood vessels. T2: Either of these conditions:

Any tumor that involves adjacent blood vessels is present. Multiple tumors, none larger than 5 centimeters (cm), are present.

T3: Either of these conditions:

More than one tumor larger than 5 cm is present. The tumor involves the major veins within the liver.

T4: Either of these conditions:

The tumor has spread to the organs near the liver (except the gallbladder). The tumor is present with perforation of the visceral peritoneum (layer of tissue that lines the abdomen).

Node. The "N" in the TNM staging abbreviation means node. Lymph nodes are tiny, beanshaped organs located all over the body that normally help fight infections and cancer as part of the body's immune system. Each type of tumor drains into lymph nodes nearby called regional lymph nodes. NX: The regional lymph nodes cannot be assessed. N0: Cancer has not spread to the regional lymph nodes. N1: The cancer has spread to the regional lymph nodes. Distant metastasis. The "M" in the TNM system indicates whether the cancer has spread to other parts of the body. MX: The tumor cannot be assessed. M0: The cancer has not metastasized. M1: There is metastasis to another part of the body.

Cancer stage grouping for intrahepatic cholangiocarcinoma Doctors assign the stage of the cancer by combining the T, N, and M classifications. Stage I: This is the earliest stage of intrahepatic cholangiocarcinoma. The tumor has not spread to the blood vessels, lymph nodes, or other parts of the body (T1, N0, M0). Stage II: The tumor involves nearby blood vessels, but has not spread to the regional lymph nodes or other parts of the body (T2, N0, M0).

Stage IIIA: The cancer has not spread beyond the liver, but the area of the cancer is larger than stage I or II, and it often has invaded nearby blood vessels (T3, N0, M0). Stage IIIB: The cancer has spread to organs near the liver, but has not spread to nearby lymph nodes or other parts of the body (T4, N0, M0). Stage IIIC: Any tumor that has spread to the regional lymph nodes, but not to other parts of the body (any T, N1, M0). Stage IV: Any tumor that has spread to other parts of the body (any T, any N, M1).

Extrahepatic cholangiocarcinoma staging Tumor. Using the TNM system, the "T" plus a letter or number (0 to 4) is used to describe the stage of extrahepatic cholangiocarcinoma. If there is more than one tumor, the lowercase letter "m" (multiple) is added to the "T" category. Specific tumor stage information is listed below: TX: The primary tumor cannot be assessed. T0: There is no evidence of a primary tumor. Tis: Refers to carcinoma (cancer) in situ. (Cancer is only in a single layer of cells lining the bile duct and not invading other parts of the bile duct wall.) T1: The tumor is confined to the bile duct. T2: The tumor has spread beyond the wall of the bile duct. T3: The tumor has spread to the liver, gallbladder, pancreas, and/or an unilateral branch (a single side) of the veins and/or arteries within the liver. T4: The tumor has spread bilaterally (both sides) to the veins or arteries within the liver and/or adjacent structures, such as the colon, stomach, duodenum, or abdominal wall. Node. The "N" in the TNM staging abbreviation means node. Lymph nodes are tiny, beanshaped organs located all over the body that normally help fight infections and cancer as part of the body's immune system. Each type of tumor drains into lymph nodes nearby called regional lymph nodes. NX: The regional lymph nodes cannot be assessed. N0: Cancer has not spread to the regional lymph nodes. N1: The cancer has spread to the regional lymph nodes.

Distant metastasis. The "M" in the TNM system indicates whether the cancer has spread to other parts of the body. MX: The tumor cannot be assessed. M0: The cancer has not metastasized. M1: There is metastasis to another part of the body.

Cancer stage grouping for extrahepatic cholangiocarcinoma Doctors assign the stage of the cancer by combining the T, N, and M classifications. Stage 0: This is the earliest stage of extrahepatic cholangiocarcinoma. The cancer is only found in one layer of cells, and has not spread (Tis, N0, M0). Stage IA: The tumor is confined to the bile duct (T1, N0, M0). Stage IB: The tumor has spread beyond the wall of the bile duct, but has not spread to the regional lymph nodes or other parts of the body (T2, N0, M0). Stage IIA: The tumor involves adjacent organs, such as the liver, gallbladder, pancreas, and/or unilateral branches of adjacent blood vessels, but has still not spread to the regional lymph nodes or other parts of the body (T3, N0, M0). Stage IIB: The tumor may or may not involve unilateral branches of adjacent blood vessels and/or the tumor involves nearby organs, such as the liver, gallbladder, and pancreas. The cancer has spread to nearby lymph nodes, but has not spread to other parts of the body (T1 or T2 or T3, N1, M0). Stage III: The tumor has spread bilaterally to adjacent blood vessels and/or adjacent structures, and may or may not have spread to the regional lymph nodes, but has not spread to other parts of the body (T4, any N, M0). Stage IV: Any tumor that has spread to other parts of the body (any T, any N, M1).

Exams and Tests

Your health care provider will perform a physical exam. Tests will be done to check for a tumor or blockage in the bile duct. These may include: Abdominal CT scan Abdominal ultrasound

CT scan-directed biopsy Cytology of samples from the bile duct Endoscopic retrograde cholangiopancreatography (ERCP) Magnetic resonance cholangiopancreatography (MRCP) Percutaneous transhepatic cholangiogram (PTCA)

Blood tests that may be done include: Liver function tests (especially alkaline phosphatase or bilirubin levels)

How is cholangiocarcinoma diagnosed?

When you see your physician you will have a routine examination. Your doctor will ask you questions about your general health and your family history of cancer and liver disease. You will also be asked about your lifestyle and habits, including drinking and smoking. Your physician may order the following tests:

Blood work. Blood tests may include a complete blood count, hematocrit, platelet count, liver function tests, Carcinoembriogenic antigen (CEA) and Carbohydrate antigen 19-9 (CA19-9), which may be elevated in patients with bile duct cancer. Abdominal ultrasound. This test helps the doctor see the tumor.

CT scan. This test identifies the tumor(s) and pinpoints their size and location in the liver, as well as their relation to the vascular / biliary structures. It also helps the doctor to determine the overall health of the liver.

Comparison of radiographic images showing cholangiocarcinoma; A, computed tomography (CT) image; B, cholangiogram (ERCP) image. Arrows designate the tumor.

MRI. This test identifies the tumor(s) and pinpoints their size and location in the liver, as well as their relation to the vascular / biliary structures. It also helps the doctor to determine the overall health of the liver. A doctor will determine whether to do a CT scan, an MRI or both. Endoscopy. Endoscopy is visual instrument that allows your physician to see the inside of the esophagus, stomach and beginning of the lower intestine without surgery.

Room setup and patient positioning for endoscopic retrograde cholangiopancreatography (ERCP)

Endoscopic Retrograde Cholangiopancreatography (ERCP). Endoscopic retrograde cholangiopancreatography is an endoscopic procedure that involves the use of fiberoptic endoscopes. You will be lightly sedated and your doctor will insert an endoscope through the mouth, down the esophagus, and into the stomach and small bowel. A smaller tube or catheter is passed through the endoscope and into the bile ducts. Dye is injected into the

ducts, and the doctor takes X-rays that can show whether a tumor is present in the bile ducts.

A, B, Position of the endoscope in the duodenum during ERCP

Percutaneous (through the skin) Transhepatic (through the liver) Cholangiogram. In this procedure, a thin needle is inserted through the skin and into the bile ducts. A dye is injected through the needle so that a contrast image will show up on X-rays. By looking at the X-rays, the doctor may be able to see whether there is a tumor in the bile ducts.

A, technique of transhepatic percutaneous cholangiography; B, corresponding percutaneous cholangiograph (after catheter is introduced)

What is the treatment for cholangiocarcinoma?

Treatment for bile duct cancer may include a combination of the following:

Surgery to remove the bile duct, and sometimes part of the liver Chemotherapy Radiation Stent placement. A stent is a tube that allows the bile, which is made by the liver, to drain more easily into the intestine if a tumor is blocking the bile duct.

A, point of percutaneous approach on a patient; B, right and left percutaneous transhepatic biliary drainage catheters restore patency around a hilar tumor VIDEO Billiary Drain: http://www.youtube.com/watch?v=dWyHMm... The subject of this short video is the Percutaneous Transhepatic Biliary Drain. The tube and the medical ... Surgical Therapy Removing biliary tract tumors surgically is the treatment of choice in cholangiocarcinoma as it is the only therapeutic option that offers the potential for cure. Surgical approaches have become increasingly sophisticated over the last decade. It has become apparent that curative treatment depends on expertise that often involves the removal of a major section of the liver. The objective is complete removal of the bile duct and tumor.

A, B, surgical technique for unilateral hepatojejunostomy with Roux-en-Y anastomosis and left hepatic lobectomy

Treatment

The treatment of cholangiocarcinoma depends on the size and location of the tumor, whether the cancer has spread, and the persons overall health. In many cases, a team of doctors will work with the patient to determine the best treatment plan. The main treatment for bile duct cancer is surgery. Radiation therapy and chemotherapy may be used if the cancer cannot be entirely removed with surgery and in cases where the edges of the tissues removed at the operation show cancer cells (also called a positive margin). Both stage III and stage IV cancers cannot be completely removed surgically. Surgery Due to the location and sensitivity of the bile duct area, surgery for cholangiocarcinoma can be difficult. If the cancer is near the liver, part of the liver will be removed, along with the bile duct, gallbladder, and sometimes part of the pancreas and small intestine. If the cancer is near the pancreas, the surgeon may need to remove some or all of the pancreas and some small intestine. In order to maintain appropriate flow of bile, the remaining part of the bile duct has to be connected to the small intestine. About 5% to 10% of people do not survive this complicated operation; others (25% to 45%) experience serious complications, such as bleeding, infection, or leaking of bile or pancreatic juices. In some cases, surgeons cannot completely remove the tumor. Therefore, the surgeon bypasses the blocked area by connecting part of the bile duct

before the blockage with a part of the small intestine beyond the blockage. The surgeon may insert a stent (a plastic or metal tube) into the bile duct to keep it open. If the doctors think that the tumor cannot be removed by surgery, a plastic or metal stent can be passed through the blockage either during the ERCP procedure or during a procedure similar to PTC. Although these procedures do not remove the tumor, they relieve its effects and people often experience long periods of time when all of their symptoms disappear and quality of life is much better. For both these procedures, the doctor will try to insert the stent internally, so the person will not be aware of its presence. Sometimes, this is not possible, and a tube will be passed through the liver to redirect the bile externally into a bag that will need regular changing. Some doctors suggest that in these situations people receive long-term antibiotics to guard against infection. Liver transplantation Complete removal of the liver and bile ducts followed by transplantation of a donor liver has been used to treat this type of cancer. This is a major procedure. Medical professionals are not in agreement about its usefulness for cholangiocarcinoma. Radiation therapy Radiation therapy uses high-energy x-rays to damage cancer cells, and several treatments may be needed. External-beam radiation (radiation given from a machine outside the body) is most often used to treat people with cholangiocarcinoma. Occasionally, internal radiation therapy may be used for cholangiocarcinomas; this involves inserting small radioactive pellets near or in the cancer by way of a tube. Side effects of radiation therapy include skin irritation, nausea, and fatigue. Radiation therapy can be used for treatment or to control symptoms and pain in advanced disease. Chemotherapy Chemotherapy is the use of drugs to kill cancer cells. Chemotherapy may be used before surgery to shrink the tumor or when surgery is not an option. In some cases, chemotherapy can shrink the tumor, but it has not yet been proven that this improves the quality of life or prolongs life. Drugs that have been used for cholangiocarcinoma include fluorouracil (5-FU, Adrucil, Efudex), cisplatin (Platinol), doxorubicin (Adriamycin, Rubex), and gemcitabine (Gemzar). Side effects depend on the drug and the dosage. Common side effects include nausea and vomiting, loss of appetite, diarrhea, fatigue, low blood count (which increases the body's susceptibility to infection), bleeding or bruising after minor cuts or injuries, numbness and tingling in the hands or feet, headaches, hair loss, and darkening of the skin and fingernails. Side effects usually go away when treatment is complete. Efforts to improve chemotherapy by investigating new drugs or new combinations of drugs are being made through clinical trials. This is often how patients with cholangiocarcinoma receive chemotherapy.

The medications used to treat cancer are continually being evaluated. Talking with your doctor is often the best way to learn about the medications youve been prescribed, their purpose, and their potential side effects or interactions with other medications. http://www.hopkinsmedicine.org/gastroenterology_hepatology/_pdfs/pancreas_biliary_trac t/cholangiocarcinoma.pdf for download of other diagnostic images