Diagnosis - Gallbladder & Bile Duct Cancer

Diagnosis

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Diagnosis

Many types of tests are used to help diagnose bile duct cancer. These can be grouped as radiology, serology, and pathology.

Radiology Tests ▼

1. Ultrasound

An improvement on the standard (transabdominal) ultrasound.

Ultrasonography of the liver and gallbladder is usually the first radiologic study used to evaluate jaundice or right-upper quadrant (abdominal) pain. During standard ultrasound the probe is placed externally on the abdomen which limits the resolution of the images. Ultrasound often detects large gallbladder cancers, but often misses smaller extrahepatic bile duct cancer. Standard CT images are often not optimal for diagnosing subtle abnormalities in the bile ducts and other organs. EUS is an improvement of this technique.

Procedure:
For an EUS, the ultrasound probe is placed in close proximity to the bile ducts by attaching it to the end of a standard gastrointestinal endoscope and passing the scope in the mouth, down the esophagus and into the stomach and duodenum . This produces a much clearer image than a transabdominal ultrasound.

Accuracy:
- EUS enables the investigator to identify abnormalities 1 cm or larger. There are small bile duct cancers that can be detected with EUS that cannot be visualized currently with a CT scan. Technological improvements are enabling a generation of more accurate images of the bile ducts and such improvements are expected to continue.
- It is the most accurate method for detecting the spread of cancer to the portal vein (not as accurate for arterial involvement).
- EUS will visualize masses of less than 1 cm but often will not be able to determine whether the mass is a cancerous. Fine needle aspiration done in conjunction with EUS may overcome this limitation.
- The main variable in the success of an EUS investigation is the experience of the endoscopist. The technique is difficult and the optimal use of this technique depends on the considerable skill of the endoscopist. Many centers now have endoscopists trained in the technique, but EUS is still not available at all medical centers.

Risks:
When done in conjunction with FNA there is a low risk of complication, 5 out of 124 patients 1.1%), all non-fatal complications. Fever, inflammation, perforation of duodenal or esophageal wall, hemorrhage of cystic tumor.

2. Computed Tomography (CT)

Scanning, which is essentially a detailed X-ray delineation of the body, is more sensitive for detecting both gallbladder and bile duct cancers.

3. MRI

Magnetic Resonance Imaging is becoming more sensitive than CT scanning, is less invasive and is slowly becoming more popular. CT and MRI have the added benefit of detecting enlarged lymph nodes near the tumors, which can suggest that a cancer has spread (metastasized) to the lymph nodes.

4. Endoscopic Retrograde Cholangio-Pancreaticography (ERCP)

Cholangiography, which involves the injection of a radioopaque dye into the biliary system, is the procedure of choice for determining the extent of tumor in the biliary tract. The procedure is done either through the skin (Percutaneous Transhepatic Cholangiography-PTC) or through an endoscope fed through the esophagus and into the duodenum.

During this procedure an X-ray is taken of the pancreatic duct and bile ducts. These ducts drain secretions from the pancreas and liver respectively. Obtaining such pictures requires that an endoscope be placed in the mouth through the esophagus and stomach, then into the duodenum.

Procedure:
The patient is sedated and given potent pain relievers (opiate) after on overnight fast. A local anesthetic is sprayed to the back of the throat. Frequently, muscle relaxants are used to relax the duodenum and ampulla (an anticholinergic drug, or glucagon, nitroglycerin). During the test patients are monitored to ensure that they are not over sedated. The monitoring includes a pulse oximeter (a probe fastened to the patient's finger that measures blood oxygen concentration) and a heart rate monitor. During the ERCP, the degree of sedation is much greater than that used for an EGD, so often the patient is asleep.

Using a modified endoscope, the investigator visualizes the duodenum on a monitor and finds the small opening where the bile duct and pancreatic duct empty into the duodenum (the ampulla of Vater). A thin catheter is passed through an opening in the endoscope and through the ampulla. Once the catheter has been placed through the opening (cannulated), a dye is injected into the pancreatic and bile ducts. This enables images of these ducts to be obtained. X-rays are taken of the abdomen over the area of the bile ducts and gallbladder and are examined on screen by the attending physicians.
Despite the medication, occasionally the patient may feel discomfort and may retch. If discomfort occurs additional pain relief is usually provided. Symptoms arising from complications may also rarely occur.

Accuracy:
Will show the indirect effects of bile duct cancer such as blockage or dilatation of the ducts and inflammation of the tissue. Similar symptoms can be caused by conditions such as chronic pancreatitis, sclerosing cholangitis, or stones in the pancreatic or bile ducts. By examining the pattern of these changes, it is possible to predict with a high degree of certainty if an abnormality is a cancer.
An ERCP can detect an abnormality suspicious of cancer in about 9 out of 10 patients who are investigated for possible adenocarcinoma. Patients who have very small cancers, less than 2 cm, that currently do not alter the main ducts of the pancreas or the bile duct will not be visible.
Occasionally, it can be very difficult to tell if an abnormality in the bile duct is due to cancer or inflammation. Tissue biopsy provides confirmation of the presence of cancer

Results:
If the test results are abnormal, a sample of biliary fluid from the bile duct or a sample of tissue by biopsy can be obtained if necessary. This can be done either during the ERCP by positioning a biopsy forceps while looking at it on screen. Alternatively, the fluid or tissue sample can be obtained by visualizing the are of concern using other imaging techniques and performing a needle biopsy (FNA).

As a Treatment:
Most importantly, if a bile duct cancer is present and the patient is not a candidate for curative surgery, therapeutic procedures can be performed using ERCP. These procedures can provide considerable relief for the patient with minimal inconvenience or risk. Bile duct cancers frequently block the bile duct that prevents the proper flow of bile from the liver. The therapeutic intervention typically alleviates symptoms caused by duct blockage such as jaundice, generalized and progressive itching, liver damage, inadequate digestion of food, a risk of bacterial infection of the blood and severe pain. Placing a stent into the bile duct to allow bile drainage can extend an individual's life and improve their quality of life. The patient does not feel the presence of the stent in their bile duct or pancreatic duct.

Risks:
The main complications of the ERCP as a diagnostic procedure are pancreatitis, infection and bleeding.

The insertion of a therapeutic stent can have complications such as bleeding, inflammation of the pancreas (pancreatitis), bile duct damage and leakage, and infection. Bleeding and pancreatitis is more likely if a large (wide-bore) stent is placed as it requires a cut to be made to enlarge the opening of the narrow ampulla where the bile and pancreatic fluid enters the duodenum (see figure). The cut primarily targets a small sphincter muscle surrounding the ampulla (hence, the procedure is termed a sphincterotomy).

Overall, less than 1 in 10 individuals will have such a complication and severe life-threatening complications are rarer (1-2%). The risk of a complication when a sphincterotomy is not performed is less (2-5%) and depends on the number and size of the stents inserted. Usually therapeutic ERCP can be done as a same day procedure without the need for an overnight hospital stay. If complications occur or are suspected hospitalization might be required. Biliary stents usually succumb to blockage after several months as a result of further cancer growth. This may require periodic stent replacement.

There is also a small risk of an allergic reaction to the dye, which contains iodine. Rarely, drugs used to relax the ampulla of Vater can have side effects such as nausea, dry mouth, flushing, urinary retention, rapid heart rate (sinus or supraventricular tachycardia), or a drop in blood pressure.

Serology Tests ▼

CA19-9

Serology refers to measurements of serum substances (markers) present in the blood which may predict the presence of tumor. The most commonly used marker is the serum CA19-9, which tends to be elevated in patients with bile duct cancer. However, this marker is not specific to bile duct cancer. It can be elevated in patients with other types of cancer and in patients without cancer. It is therefore not a very good screening test for the general public.

This is a tumor marker for bile duct cancer that is measured through a blood test. It is useful in assisting with an initial diagnosis. However, it is more useful in measuring the effectiveness of cancer treatment by studying the patient's CA19-9 levels over time.

In general, before surgery, the higher the CA19-9 level is (normal CA 19-9 level is 40 units per milliliter), the larger the tumor is and the less chance that the tumor is resectable. For the purposes of evaluating treatment, a decreasing or stable CA19-9 level generally indicates an improved prognosis and an increasing level indicates the progression of disease.

Currently, there are not sufficiently accurate diagnostic blood tests for bile duct cancer. Very few cancers, such as prostate and liver cancers, can be confidently diagnosed solely on the basis of blood test results. Perfecting a suitable blood test for bile duct cancer is an area of active research because it would enable screening for individuals considered at-risk.

Accuracy:
CA19-9 is elevated in the blood of about 90% of individuals with bile duct cancer. Other blood tests such as CEA can be used in combination with CA 19-9 to improve the accuracy of the test. Supplemental imaging studies and tissue samples are required with CA19-9 levels for a definitive diagnosis.

CA19-9 can be used to track treatment progress of previously diagnosed bile duct cancer patients. This blood test in conjunction with periodic CT scans will show whether the cancer is in remission or is continuing to grow.

Results:
If your doctor suspects bile duct cancer, an abnormal CA 19-9 blood level will increase the suspicion. However, there are benign diseases of the bile ducts and pancreas that occasionally result in elevated CA 19-9 levels. For this reason CA 19-9 is not considered a diagnostic test.

Pathology Tests ▼

Pathology is the gold standard for the diagnosis of cancer. The diagnosis can sometimes be made by cytopathology, the study of individual cells spread into a thin layer onto glass microscopic slides.

1. Fine Needle Aspiration (FNA)

Bile duct brushings can be performed through an endoscope (a special scope which is inserted into the mouth and passed into the first portion of the intestine) to detect malignant cells. If a mass is present, fine needle aspiration of it can be performed; this involves guiding a thin needle into the lesion, and gently sucking out cells for microscopic examination. These procedures have the benefit of not requiring an operation or general anesthesia.

A method to biopsy, obtain cells, for examination under the microsope.

FNA, performed in conjunction with a CT or MRI imaging, enables pathologists to determine the nature of a suspicious biliary tract abnormality.

Procedure:
It is a surprisingly safe procedure that involves passing a small needle directly through the skin or through an endoscope. The CT or MRI imaging allows the doctor to see where the needle is going. This is because the needle used has a very small bore. This sometimes means that the small amount of tissue obtained is insufficient for the pathologist to establish a diagnosis.

Accuracy:
A diagnosis of biliary cancer based on a FNA is highly accurate, approaching 99%. However, it is only between 50-70% accurate in determining whether the cancer is benign or malignant.
Because the amount of tissue obtained is so small, the absence of malignant cells in the sample cannot exclude the possibility of malignant disease altogether.

Risks:
Complications such as bleeding or infection occur very rarely, less than 1% of patients.

Note:
Another technique used to obtain cells from the biliary tree for examination is bile duct brushing. In this procedure, through an endoscope, a brush is used to remove cells from the inside of the bile duct. These cells are smeared onto a slide and examined under the microscope.

2. Biopsy

Biopsy of the biliary tract is the more common means of detecting these tumors. Sometimes the biopsies can be performed through the endoscope; other times exploratory laparotomy, in which the surgeon makes an incision in the abdominal wall and enters the abdomen, is performed, under general anesthesia.

A slender hollow tube inserted into the body to relieve a blockage. For example, bile duct cancers often narrow the bile duct. This can block the flow of bile and cause the patient to become jaundiced. In these cases the flow of bile can be reestablished by placing a stent into the bile duct, through the area of blockage.

Excessive amounts of fat in the stool. Sometimes this can appear as an oil slick on top of the toilet water after the patient has had a bowel movement.

Stage I - refers to tumors that are confined to the bile duct and its fibromuscular wall.

Stage II - refers to tumors that have extended into the connective tissues immediately around the bile duct.

Stage III - refers to tumors that have spread to regional lymph nodes.

Stage IV A - refers to tumors that have directly invaded an adjacent organ (like the liver, pancreas, duodenum, colon, or stomach).

Stage IV B - refers to tumors that have spread (metastasized) to distant sites.

Stage I - refers to tumors confined to the gallbladder and its muscular wall.

Stage II - cancers have extended into the tissues immediately around the gallbladder.

Stage III - tumors have spread to regional lymph nodes or are tumors which have directly invaded an adjacent organ.

Stage IV A - refers to tumors that extend more than 2 cm into the liver and/or into 2 or more adjacent organs.

Stage IV B - have spread (metastasized) to distant sites.

A classification system used to describe the extent of disease. In general, the lower the stage, the better the prognosis.

A flat, scale-like cell.

A maroon, rounded organ in the upper left part of the abdomen, near the tail of the pancreas. This organ is part of your immune system and filters the lymph and blood in your body.

A long (20 foot) tube that stretches from the stomach to the large intestine. It helps absorb nutrients from food as the food is transported to the large intestine. There are three sections: the duodenum, the jejunum and the ileum. Due to its proximity to the pancreas, the duodenum is the section most often affected by pancreatic and distal common bile duct cancers.

An infection of the blood.

A malignant tumor that mimics connective tissues (bone, cartilage, muscle) under the microscope.

An oblong organ located between the stomach and the spine. The pancreas secretes enzymes needed for the digestion of food and it produces hormones such as insulin and glucagon which help control blood sugar.

Any treatment that reduces the severity of a disease or its symptoms.

A term used to describe certain tumors which grow in finger-like projections. Pathologists mostly use this term.

A medical doctor specially trained to study disease processes.

Around the ampulla of Vater. The peri-ampullary region is comprised of 4 structures; the ampulla, the duodenum, the bile duct and the head of the pancreas. It is sometimes difficult to tell which structure a tumor originated in. In such cases the diagnosis will be a peri-ampullary tumor.

The biochemical study of plants; concerned with the identification, biosynthesis, metabolism of chemical constituents of plants; especially in regards to natural products.

A cancer found in the organ it started in. A primary cancer of the esophagus is one that started in the esophagus as opposed to a cancer that started somewhere else and only later spread to the esophagus.

A forecast for the probable outcome of a disease based on the experience of large numbers of other patients with similar stage disease. Importantly, making a prognosis is not an exact science. Some patients with poor prognosis beat the odds and live longer than anyone would have predicted. Steve Dunn's Cancer Guide has an excellent article on statistics and prognoses and stories of other cancer patients.

A thick ring of muscle (a sphincter) between the stomach and duodenum. This sphincter helps control the release of the stomach contents into the small intestine.

Able to be removed surgically.

The use of high-energy waves similar to x-rays to treat a cancer. Radiation therapy is usually used to treat a local area of disease and often is given in combination with chemotherapy.

The thin tip of gland in the left part of abdomen, near the spleen.

An inflammation of the veins accompanied by thrombus formation. It is sometimes referred to as Trousseau's sign.

A clot within the cardiovascular system. It may occlude (block) the vessel or may be attached to the wall of the vessel without blocking the blood flow.

This term simply refers to a mass or neoplasm. For example, a collection of pus is a tumor. This is a general term that can refer to benign or malignant growths.

A painless procedure in which high frequency sound waves are used to generate pictures of the inside of the body.

The part of the gland that bends backwards and underneath the body of the pancreas. Two very important blood vessels, the superior mesenteric artery and vein, cross in front of this process.

Unable to be surgically removed.

This is a new type of treatment, largely still experimental. It is a medication made of killed or weakened cells, organisms or manufactured materials, which is used to boost the body's immune system. Ideally, this will allow the body to fight and kill the cancer cells more effectively. Vaccines include whole killed cancer cells or specific proteins from the cancer.

There are several variations of this procedure. It typically involves the surgical removal of the head of the pancreas, a portion of the duodenum and a portion of the bile ducts.

A technique that surgeons can use to visualize and even biopsy (take tissue samples of) organs inside of the abdomen without making large incisions. Very small incisions are made in the belly and small tubes (called trocars) are then inserted. Gas is pumped in through one of the tubes to create enough space to work in. The surgeon inserts a small camera through one of the tubes and examines the lining and contents of the abdominal cavity by looking at the projected image on the television screen. With specially designed laparascopic instruments, biopsies and fluid samples can be taken for examination. Some surgeons feel that this technique can help "stage" a patient less invasively than with open surgery.

The largest organ in the body, located in the right upper part of the abdomen. It performs many life-maintaining functions including the production of bile. It detoxifies the blood of drugs, alcohol and other harmful chemical. It processes nutrients absorbed by the intestine and stores essential nutrients, vitamins and minerals. Bilirubin is a chemical produced when old or damaged blood cells breakdown. The liver chemically process the bilirubin so that it can dissolve in water and be excreted through the bile. When this process is disrupted, jaundice can develop.

A primary cancer that has spread to regional lymph nodes and/or resectable (removable) tissues. Removable tissues include some lymph nodes that are routinely removed in some surgical treatments for cancer.

Normal, round, raisin to grape-sized collections of lymphocytes (white blood cells) found throughout the body. Lymph nodes are connected to each other by lymphatic vessels. They normally help fight infection, but also are one of the first sites to which cancers spread. In general, the spread of cancer to lymph nodes portends a worse prognosis for the patient. There are exceptions to this.

A painless method for taking pictures of internal organs. A tube-like machine with a powerful magnet generates images of the inside of the body.

A cancer that has the potential of invading nearby tissues, spreading to other organs (metastasizing) and possibly leading to the patient's death.

A cancer that has spread from one organ to another. Bile duct and gallbladder cancers most frequently metastasize to the liver. In general, cancers that have metastasized are generally not treated surgically, but instead are treated with chemotherapy and/or radiation therapy.

An alteration in the DNA of a cell.

The thin section between the head and the body of the gland.

Chemotherapy and radiation therapy given to patients before surgery. Some centers feel that the use of neoadjuvant therapy improves local and regional control of disease and that it may make more patients surgical candidates.

An abnormal new growth of tissue that grows more rapidly than normal cells and will continue to grow if not treated. These growths will compete with normal cells for nutrients. This is a general term that can refer to benign or malignant growths. It is almost a synonym for the word tumor, which means a mass or growth.

A medical doctor who specializes in the treatment of tumors.

A surgically created opening in an organ that can also be referred to as an anastamosis.

The name given to cancers arising at the confluence of the left and right bile ducts of the liver (left and right hepatic ducts)

Yellowing of the skin or whites of the eyes caused by the accumulation of bile pigments. (usually due to an obstruction of the bile ducts.)

A hormone produced by the endocrine islets of Langerhans cells of the pancreas. It acts to lower blood sugar levels.

A term used to indicate that cancerous cells are present in the lining of an organ but have not spread to the "meat" of the tissue.

The widest part of the pancreas. It is found in the right part of abdomen, nestled in the curve of the duodenum, which forms an impression in the side of the pancreas.

Surgical removal of a structure or part of a structure. For example, pancreatectomy is the surgical removal of the pancreas (or a portion of it), and esophagectomy is removal of the esophagus.

These are specialized cells that produce hormones released into the bloodstream. For example, the islets of Langerhans are endocrine cells in the pancreas that produce the hormone insulin. This hormone helps control blood sugar(glucose) levels.

Some rare tumors of the pancreas, the endocrine (Islet Cell) tumors, can produce these same hormones. It is very important that these rare tumors be properly diagnosed because it will determine the treatment and prognosis.

A medical doctor who specializes in the treatment of hormonal abnormalities.

A chemical that causes a reaction in other substances, in this case as a part of the digestive process.

A test used to visualize and examine the pancreas and bile ducts. A tube is inserted through a patient's nose (or throat), down through the esophagus and stomach then into the small intestine (duodenum). There, a small probe is inserted into the ampulla of Vater. A dye is injected through the probe and into the pancreatic and bile ducts. X-rays are then taken and the pancreatic and bile ducts can be seen as white structures (this is because the injected dye is opaque. Because cancers often block the pancreatic and/or bile ducts, this technique can be useful in establishing a diagnosis of a cancer.

The exocrine cells (acinar cells) of the pancreas produce and transport chemicals that will exit the body through the digestive system.

The chemicals that the exocrine cells produce are called enzymes. They are secreted in the duodenum where they assist in the digestion of food.

A hormone produced by the endocrine (islets of Langerhans) cells of the pancreas. When blood sugar levels are low, glucagon acts to raise blood sugar levels.

The trade name for gemcitabine. A chemotherapy drug frequently used to treat pancreatic cancer. It has been shown, in controlled clinical trials, to improve quality of life.

A green pear-shaped organ located on the right side of the abdomen just under the liver. The gallbladder is essentially a reservoir for holding bile.

A chemotherapeutic drug used to treat pancreatic cancer.

The first portion of the small intestine. It is about 1 foot long.

A small anatomic structure. This is essentially a tube that carries various bodily fluids.

The part of every cell that carries all genetic information.

A dome shaped muscle that separates the lungs and heart from the abdomen. This muscle assists in breathing.

The condition or disease in which the body is unable to appropriately control blood sugar(glucose) levels. This may be caused by failure of the pancreas to produce adequate amounts of insulin.

A fluid filled sac. Some tumors of the biliary tree, including mucinous cystadenocarcinomas are cystic. These have a distinct appearance in CT scans. They are important to recognize because the treatment of cystic tumors can differ from that for solid tumors.

A dye, taken by mouth or injected, that is sometimes used during x-ray examinations to highlight areas that otherwise might not be seen.

A series of x-ray pictures taken by a machine that encircles the body like a giant tube. Computers are then used to generate cross-sectional images of the inside of the body.

Surgical removal of the gallbladder.

A cancer of the intrahepatic (within the liver) portion of the bile ducts.

The treatment of a cancer by chemicals. For bile duct and gallbladder cancers these include: 5-flurouracil, leukovorin, mitomicin C, and others.

A small, flexible tube inserted into the body to inject or suck out fluids.

A malignant (cancerous) new growth. These tumors infiltrate into surrounding tissues and, if untreated, will spread to other organs, and may eventually lead to the patient's death.

A cancer-causing agent.

A malignant tumor. It has the potential of invading into the adjacent tissues, spreading to other organs and may eventually lead to the patient's death.

A dramatic weight loss and general wasting that occurs during chronic disease.

A blood marker for pancreas and biliary cancers. It is not a good screening test for diagnosing possible cancers. However, it can be useful in following the progress of patients known to have a cancer by measuring how their cancer is responding to treatment.

The middle part of gland between the neck and the tail. The superior mesenteric blood vessels run behind this part of the gland.

A primitive tumor that develops in childhood.

The removal and microscopic examination of a tissue sample.

Relating to bile or the bile duct system.

A green fluid produced by the liver that helps digest fats. It is transported from the liver to the duodenum by the bile duct. When the flow of bile is blocked, patients may become jaundiced (yellow skinned).

Tumors which are non-cancerous. These generally grow slowly and do not invade adjacent organs or spread (metastasize) beyond the bile ducts or gallbladdder.

The collection of excess amounts of fluid in the abdominal cavity (belly). It often is a sign that the cancer has spread to either the liver or the portal vein that goes to the liver. If normal liver function is affected, a complex set of biochemical checks and balances is disrupted and abnormal amounts of fluid are retained.

The large artery that carries oxygen-rich blood from the heart. It descends into the abdomen where it gives off many branches to supply the organs. The superior mesenteric artery is a major branch of the aorta that is a common site of cancer metastases.

A radiographic technique used to visualize blood vessels. A contrast medium (a dye) is usually injected into the vessels to make them appear white on the x-rays.

A condition marked by a diminished apetite and aversion to food. Often results in physical signs of wasting.

A condition characterized by a deficiency in red blood cells. This can lead to fatigue among other symptoms.

A surgical joining of two hollow structures. It is similar to attaching two ends of a garden hose. For example, a gastrojejunostomy is a surgical procedure that connects the stomach and the jejunum (small intestine.)

This widening of the pancreatic duct is an landmark for physicians. It is where the bile duct and pancreatic duct join before draining into the duodenum (small intestine). Tumors in the head of the pancreas may squeeze this duct partially or completely closed. This can lead to problems with digestion and jaundice.

Chemotherapy given to patients after their cancers have been surgically removed. It is a secondary treatment given to supplement surgical treatment.

A benign (non-cancerous) tumor made up of cells that form glands (collections of cells surrounding an empty space.)

The form of cancer that most people are talking about when they refer to "cancer of the bile ducts."

Microscopically, adenocarcinomas form glands. These tumors can grow large enough to invade nerves which can cause back pain. They also frequently spread (metastasize) to the liver or lymph nodes. If this happens the tumor may be considered unresectable.

A pus-filled cavity.

The portion of the body between the diaphragm and the pelvis.