GALLBLADDER CANCER TREATMENT INFORMATION

What does the Biliary System Do?

The gallbladder is an organ in the abdomen which collects bile drained by the liver into this sac,
which is connected to the liver by the cytic duct . It is then transported as needed, through the
common bile duct into the small intestine. It then travels to meet the draining pancreatic duct at
the "Ampulla of Vater". The bile and pancreatic secretions then pass into the first portion of the
small intestine ("duodenum") through the sphincter of Odi", a small drainage hole. Bile is a
putrid greenish substance which helps digest fats, by coating them and breaking them down. This
process is called emulsification. Digested fats can then be absorbed into the bloodstream and
used to make energy for the body. Any inflammation of the bile system is called "cholangitis",
while specific inflammation of the gallbladder only is called"cholescystitis".

Inflammation can be caused caused by germs, drugs, radiation, immune diseases, or most
commonly a blockage of the bile flow by gallstones or a tumor. When the bile flow is blocked,
for whatever reason, it tends to backflow into the bloodstream and remain unprocessed
("unconjugated") by the liver.

The form which bile takes in the bloodstream is called "bilirubin" and there is normally some
present (<1.4 mg/dL) in the blood serum. When the bilirubin increases, the whites of the eyes
("sclera") and then skin turn yellow, called "jaundice", while the stool becomes much lighter or
even white. Digestion of fats is impaired, leading to loose, smelly stools ("steatorrhea"). The
blockage may affect the pancreas, causing pancreatitis, and paralyze the local digestive tract
("gallstone ileus"). The biliary system is surrounded by important organs-- the pancreas,
esophagus, liver, bowel, spinal column, and major blood vessels. Infection or cancers can
directly invade these areas with relative ease ("local spread"). Furthermore, there is a system
of"lymph channels" draining blood serum from the liver and gallbladder, and transporting this
serum to nearby"lymph nodes".

The lymph nodes are normally pea-sized "filters", full of white blood blood cells, which purify
the blood serum. The lymph nodes are interconnected and eventually return the purified serum to
the bloodstream. When lymph nodes are invaded by infection or cancer, they swell
("lymphadenopathy") and when overwhelmed act as a route of spread ("lymphogenous spread") .
Moreover, the bile duct area, and digestive system in general, has a rich blood supply from both
major arteries and draining veins. These blood vessels can act to carry cancers or infections to
distant parts of the body ("hematogenous spread" ). The point is that initially local cancers of the
bile system may be spread through the body ("disseminated") with relative ease. Most non-
cancerous gallbladder and bile duct problems occur in women with the "Five F's"-- Female,
Forty to Fifty years old, Fertile, Fat, and Flatulent (a medical student's mnemonic). More rarely,
the "biliary system" (gallbladder and bile ducts) will be afflicted with cancer.

What is Biliary Cancer?

Like all organs, the biliary system is made up of individual "cells" which are arranged to form
"tissues". The cells in the bile duct system grow rapidly in womb life, childhood and through
puberty. In adulthood, they divide much more slowly, to replace those that die of injury or old
age. Like all cell division in the body, this process is tightly controlled to proceed in an orderly
manner. This control is exerted by the genetic material ("genes") in each cell, which are in turn
are made up of "DNA" . Biliary cancer starts within a single cell. Something changes the control
mechanisms within this cell, the genes become damaged, and it starts dividing in a rapid and
disorganized manner . Eventually these abnormal cells for a clump, or"tumor".

A tumor is merely a swelling, as isn't necessarily cancerous. A "benign" tumor just grows in it's
local area, and although it may become very large it doesn't spread and isn't cancer . By contrast,
a malignant tumor is cancer and has a capacity to spread to any area of the body. The process of
spread of called"metastasis" . Thus, any metastatic tumor is by definition cancerous. Only a
cancer which starts in the biliary system is called "primary" biliary cancer. A cancer that has
spread there from another area (i.e. lung, colon, ovary) is named for it's place of origination.

How Common is Biliary Cancer?

Hepatobiliary cancer (meaning in either the liver or bile ducts) occurs in 20,000 new patients and
causes 15,000 deaths each year in the United States. About 3000 of the cases are in the liver
itself, the remaining 17,000 cases are in the Gall Bladder and bile drainage ducts. Bile duct
cancer is equally common in males and females, and the average patient is 60 years old.
However, gall bladder cancer is three times more common in women than men, (similar to the
higher rate of gallstones in women). Any biliary cancer is rare (<1% of cases) in patients under
age 45.

What are the Types of Tumors?

The most common types of benign bile duct tumors are hemangiomas (which are a cluster of
abnormal blood vessels forming a swelling), and adenomas (which are clumps or knots of
tissue). The most common malignant bile duct cancer is adenocarcinoma (90% of cases) which
arises from the bile duct cells themselves. Cholangiocarcinoma (35% of cases) arises from bile
ducts in the liver as they proceed down toward the gallbladder. A Klatskin tumor is a
cholangiocarcinoma located nearby where the gallbladder meets the liver. Rarer types of bile
duct cancer include mixed hepatocellular carcinoma and adenocarcinoma (both liver and bile
duct cancer together),lymphomas (arising from the immune system cells) and sarcomas (from the
muscular wall of the gallbladder).

What are the symptoms of Biliary Cancer?

Very early biliary cancer will produce no symptoms, since the tumor is too small to interfere with
normal organ function. When symptoms do arise, they are commonly as resulting from a massive
tumor growing in the bile ducts, up into the liver, or even liver failure. Most patients have
advanced disease when diagnosed Symptoms include:
1.Pain in the right upper abdominal area caused by stretching of the liver's capsule, which is rich
in nerves. Also, a blocked, swollen gallbladder hurts.
2. Weight Loss and loss of appetite; the liver and biliary systems are digestive organs. Failure to
emulsify fats (at 9 Calories per gram) causes malnutrition.
3.Fatigue and eventually coma from liver failure, buildup of ammonia in the body.
The liver pulls ammonia off of amino acids (protein) we eat and turns it to urea.
4. Jaundice and light stools, from blockage of the bile draining system.
5. Itching ("pruritis") from buildup of bile ("bilirubin") in the blood.
6. Fever from secondary bacterial infection of the blocked biliary tract.
7. Digestion problems like diarrhea and gas when eating fatty foods.
8. Pancreatitis with blood sugar problems ("diabetes") and abdominal pain.
9. Liver failure in advanced disease, symptoms include body swelling, easy bruising, spider-like
veins on the skin, and breast growth in males.
10. Signs of Distant Spread such as bone pain or Neurological symptoms from spread to other
areas. Lung, liver, bone and brain are common sites to spread.

The time until the symptoms become noticeable tends to be longer with cancers in the lower
portion of the biliary system than in the upper portion (nearer the liver). About 70% of cancers
arise in the upper portion of the biliary system, and 15% each in the middle and lower portions
(close to the small bower).

Bile is manufactured in the liver and helps the body digest fats. The bile ducts course throughout
the liver collecting bile, then travel to the gall bladder where bile is stored. When bile is needed,
such as after a fatty meal, it is released into the small intestine via another duct which connects
the gallbladder to the small intestine.
Bile duct cancers, also called cholangiocarcinomas, may arise in many locations in and around
the liver. They are rare, affecting only 16,600 people in the United States per year. The only
definitive treatment is the complete surgical removal of the tumor, which is not often possible. If
the cancer cannot be entirely removed, the principal goals of therapy become the relief of
symptoms caused by the accumulation of bile, and relief from pain.

How It Spreads
Bile duct cancer tends to spread into the adjacent liver, along the bile duct surface and through
the lymph system to lymph nodes in the region of the liver. Tumors in the bile duct leading from
the gall bladder to the common bile duct (cystic duct) can spread to involve the gall bladder.
Ultimately, other lymph nodes as well as other organs within the abdomen may become
involved.

What Causes It
The cause is unknown although people with chronic inflammatory processes such as ulcerative
colitis or parasitic infections of the bile ducts, or with congenital abnormalities of the bile ducts
are at higher risk for developing this cancer. No one cause has been clearly demonstrated.

Common Signs and Symptoms

There are no signs or symptoms unique to bile duct cancer. Even if the findings associated with
bile duct cancer are present, other explanations, such as gallstones, are far more likely.
Symptoms generally develop slowly and are often subtle. Jaundice (the skin turning yellow) and
itching are the most common signs. Jaundice is caused by the accumulation in the skin of a
component of bile (bilirubin) that normally empties into the intestines after traveling through the
bile ducts.
Bloating, weight loss, decreased appetite, fever, nausea or an enlarging abdominal mass are all
signs that may be attributable to bile duct cancer. Pain usually signifies advanced disease.

Staging and Treatments

A TNM staging system is used for bile duct cancer, but when deciding which treatment option to
use there are really only two stages - localized and unresectable disease.
The optimal treatment for bile duct cancer is surgery. Unfortunately, by the time symptoms
develop, the cancer has usually spread throughout the bile ducts and into the liver, meaning that
the tumor cannot be entirely removed.
Chemotherapy and radiation therapy are occasionally useful to relieve symptoms. Although they
have not been shown to be effective in curing the cancer, these measures can be taken to
maintain the quality of life.

Signs and Diagnostic

Stage Treatments Survival
Symptoms Procedures

Early Generally No screening Surgery followed by radiation Unknown

none methods therapy
Tumor is isolated available
to the bile duct and
is generally too
small to be
detected

Resectable Generally Blood tests: Surgery: Surgery can be done 5 years:

none hemoglobin with hopes of a cure. The extent of less than
Tumor is confined (anemia); white surgery depends on the location 25%
to the bile duct. It blood count; and size of the tumor. If the tumor
is quite rare to find abnormal liver is isolated to either the right or left
a bile duct cancer function tests; bile duct, it may be possible to
at this limited stage abnormal clotting remove the tumor and its
because symptoms (PT, PTT) tests accompanying lobe of the liver.
of bile flow Tumor involving both ducts or
obstruction are rare Ultrasound: their junction create more
Enlarged bile problems and more difficult
duct due to operation. The overall health of
blockage the patient is important when
determining if surgery is possible.
MRI: May help Radiation therapy is often
determine if bile recommended following surgery
duct cancer can
be surgically Chemotherapy: Studies have not
removed shown that chemotherapy
prolongs survival. Mitomycin C or
PTC: An 5-FU, however, may cause tumor
injected dye shrinkage in 20-25% of patients.
Even with shrinkage, however,
 followed by x- patients may not be better off as
ray may reveal the tumor ultimately regrows and
site of blockage treatment has side effects.

ERCP: Along Radiation therapy: If the tumor

with PTC, this is fairly small, it may be treated
may help define with radiation without much
the site and cause damage to the surrounding liver. It
of obstruction may also apply to patients with
and correctly small or microscopic deposits of
predict the tumor following surgery
presence of
cancer 90% of
the time

Chest x-ray: If
cancer is
confirmed, this
should be done to
look for tumor
spread to the
lung

Unresectable Jaundice, There are no standard treatments, 2 years:

itching, bile so chemotherapy and/or radiation less than
Tumor has spread infections, therapy clinical trials should be 1%
to organs beyond pain, considered. Palliative measures,
the bile duct appetite, such as relieving symptoms of
(lymph nodes, edema, itching or infection by surgical
liver) and cannot nausea, bypass system for bile may be
be removed insomnia done.

Supportive Therapies.
Problems associated with jaundice can include severe itching and infections in the bile. If
the drainage procedures described above are not effective, itching will often be relieved by
Benadryl, Atarax or cholestyramine.

Large doses of narcotics may be needed to relieve pain. Such drugs may have excessive side
effects, since they are eliminated by the liver, which may not be functioning properly.

Non-steroidal anti-inflammatory drugs may be surprisingly effective even against the pain
associated with bile duct cancer.
Frequent small meals may be necessary to get enough nutrition since an abdominal mass
may reduce the size of the stomach.
Water pills (diuretics) can reduce fluid in the abdomen or legs. They may cause significant
imbalance in kidney function, however, and can create problems if not carefully monitored
and adjusted.

Nausea will often be relieved by standard medications, including suppositories.

Loss of appetite may be helped by a drug called Megace.

Sleep disturbances are common, but most sleeping pills are broken down by the liver, so
they should be used carefully.

The Most Important Questions to Ask Your Doctor.

1. Should I see another physician to confirm that this tumor can or cannot be removed?
2. Can the drainage of my bile ducts be done through my intestines so I won't have to have
a tube coming out through my skin?
3. Am I a candidate for an investigational therapy at another medical center?
4. How sick will radiation and/or chemotherapy make me, and does the potential benefit
make it worthwhile?
5. Is the treatment worthwhile if the tumor is too advanced for surgery?
6. Can anything be done to improve the quality of my life?

People don't think about their gallbladder unless it is diseased with gallstones, or it
develops cancer. In the past gallbladder cancer was almost always fatal, since it tended to
be advanced when first be diagnosed and effective treatments were not available.

There has been much research in the past decade on treating gallbladder and other biliary
tract cancers. It is crucial to make the right choices in treating this condition. It can make
the difference between life and death. Understanding your options for gallbladder cancer
will give you the peace-of-mind knowing that you have done everything possible to fight
this disease successfully.