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.
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 causes15,000 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 Causes or Increases Risk for Bile Duct Cancer?
The exact reason why any one person gets bile duct cancer and another doesn't is
unknown . However, the below"risk factors" have been noted in many patients:
Risk Factors for Biliary Cancer:
Chronic Inflammation of the bile duct system is associated with bile duct cancer:
a.Liver Flukes (worms) are the most common cause of bile duct cancers worldwide. Specifically, these worms are Clonorchis sinensis
and Opisthorchis
viverrini.
However, these are rare in the U.S.A.
b. Liver Stones of the bile duct system ("hepatolithiasis") caused by the bile drying
up and forming a hard stone, much like a gallstone.
c. Ulcerative Colitis can lead to inflammation around the bile ducts, but less than
1% of patients with ulcerative colitis get bile duct cancers.
d. Gallstones are found in up to 90% of patients with gall-bladder cancer.
e. Calcification of the gallbladder forms a "porcelain gallbladder" can lead to bile
cancer in 60% of patients with this condition.
f. Congenital malformation (from birth) of the biliary tract is a risk for later
cancer.
For the mixed forms (liver cancer and bile duct cancer) risk is increased by:
1. Chronic Hepatitis can lead to changes in the liver cells associated
with the most common type of liver cancer, hepatocellular carcinoma (HCC).
a)Hepatitis B -- evidence of prior infection is found in 75% of liver cancer
patients worldwide. It can lead to cirrhosis, below. The
more common
Hepatitis Aisn't associated with liver cancer.
b)Carcinogens (chemicals inducing cancer) such as aflatoxin food
contamination (used by Iraq on the Kurds) and nitrosamines.
2. Cirrhosis of the liver (the liver can shrink up and become fibrous and fatty
in response to chronic irritation). Causes of cirrhosis include:
a) Alcoholism-- alcoholic cirrhosis leads to 5% of liver cancer.
b)Hemochromatosis is an overload of iron in the liver. 20% of patients
who get cirrhosis from the overload may develop HCC.
c)Alpha1- antitrypsin deficiency is a rare condition where a necessary
enzyme is lacking to break down waste products in the
liver and lung.
HCC can develop in 40% of patients who get this type
of cirrhosis.
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.
Liver failure in advanced disease, symptoms include body swelling, easy
bruising, spider-like veins on the skin, and breast growth in males.
9.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).
How is Biliary Cancer Diagnosed and Evaluated?
Since biliary cancer is unusual, and it's symptoms mimic many other conditions,
there is commonly a delay in making the diagnosis while the cancer grows larger. Unfortunately, most patients have advanced disease by the time the diagnosis is made.
Important steps to diagnosing liver cancer include:
1 . A high"index of suspicion" in patients with a history of chronic gallstones,
toxin exposure, ulcerative colitis or chronic hepatitis.
2 . A complete physical exam especially looking for signs of a tumor in the upper
right abdomen, gallbladder enlargement, liver swelling ("hepatomegaly"),
yellow
sclera (early jaundice), and signs of liver failure like body swelling and
bruising.
The physician looks for enlarged lymph nodes in the armpit ("axillary") and
area
above the collarbone ("supraclavicular") and navel ("umbilical") nodes.
3 . Blood tests including a complete blood count (CBC) to look for anemia or infection, and blood chemistries which tell about liver and bile drainage. The
most
commonly elevated blood tests with jaundice are bilirubin and alkaline phosphatase, with liver damage they are AST, ALT, and GGT. Also, a hepatitis panel
is appropriate. In patients with HCC, a "tumor marker" blood test called"AFP"
(alpha-fetoprotein) elevated in over 50%, but not in patients with pure biliary
adenocarcinoma. Another tumor marker called CA19-9 is high in 90% of patients
with cholangiocarcinoma, but is normal in patients with pure liver HCC. Unfortunately, it is not specific for biliary cancer since it may be high in pancreas
cancer.
4 . Radiologic tests, like Ultrasound, are useful for looking at the shape of the liver,
the bile duct system, identifying a tumor, and tracking the progress of
therapy.
Ultrasound doesn't use any radiation (just sound waves) and is very safe
in
children and pregnant women. However, the results are very dependent upon
the skill of the technician performing the test, and if something is found
then a
CT scan will be ordered anyway. A CT scan is very accurate for detecting
tumors larger than 1 cm, it does use radiation like a series of multiple X-rays
which are joined together. The CT scan is not technician dependent, and
is
very good for showing extension of the tumor into other organs and enlarged
lymph glands in the vicinity of the tumor, which can represent spread to
them. One-half of all patients with biliary cancer have lymph node spread at diagnosis.
The CT scan may be done with "contrast" injected into an arm vein, highlighting
the blood vessels for a better view. Insist on"omnipaque" brand contrast or
equivalent, it's more expensive but more comfortable and less likely to
cause
allergic reactions or kidney problems.
Other tests to visualize the tumor are arteriography, where some contrast dye
is injected and special X-rays taken that show the shape of the tumor's
blood
vessels. Another test is theMRI scan which uses no radiation, shows organs in
the abdomen very clearly, but is expensive ($1000) and requires the patient
to lie
almost perfectly still for an hour to be accurate. Contrast may also be
used for
the MRI to highlight blood vessels, it is called"gadolinium" and put into a vein.
These tests are gotten to evaluate a patient for possible surgery or check
their
response to therapy. A percutaneous cholangiography (PTC) test is where
some dye is injected directly into the bile duct system and special X-rays
are
taken to visualize the ducts. Blockages from tumor may be seen, analogous
to a cardiac catheterization looking for blockages in the heart. More common
for initial d diagnosis is anEndoscopic Retrograde Cholangiopancreatograpy
(ERCP) where a tube is placed through the mouth, down into the stomach and
small intestine, and guided into the common bile duct. The surgeon can
then
see a tumor there and even take cuttings or brushings of it for a sample.
5 . The only way to absolutely diagnose any cancer is by getting a piece of it for
analysis, that is a biopsy of the tumor. This biopsy may be obtained by afine-needle under local anesthesia, in the radiology department using ultrasound
or CT scan to guide the needle into the tumor. Several samples are usually
taken for accuracy. Risks of biopsy include spilling the tumor or bleeding
the
from puncturing blood vessels in the tumor, this may require an emergency
operation to stop bleeding. Overall fine-needle biopsy is safe and effective.
Alternatively, theERCP test described above can be used to get a biopsy.
The biopsy material is examined by a "pathologist", a physician specializing
in diagnosing disease from tissue samples. The pathologist stains the
tissue
samples and examines them under a microscope. If cancer is detected,
(s)he
will specify the particular type, and the grade (I,II or III) which tells how aggressive the cancer is likely to be. Higher grade cancers (III) are worse
than lower
grade (I) ones, since they are more likely to spread. It is important
to absolutely
identify the tumor as malignant, for otherwise 10% of patients who have
only
benign bile duct stricture or other non-cancerous conditions will get
unnecessary treatment.
How is the Extent of Biliary Cancer Gauged?
As for all cancers, the extent of biliary cancer is given by the "Stage" . The staging most commonly used is from the American Joint Cancer Committee ("AJCC"):
For Gallbladder Cancer:
Stage I means the cancer involves the gallbladder's linings, either the inner lining
("mucosa") or the middle muscular lining ("muscularis").
Stage II means cancer involves even the outer lining
("serosa") but has not spread
beyond the gallbladder proper.
Stage III means cancer either involves one organ directly outside the gallbladder
(up to 2 cm. into the liver), or local lymph nodes, or both.
Stage IVA means the cancer invades more than 2 cm. up into the liver or invades
more than one local organ
(i.e. stomach, duodenum, colon, pancreas).
Stage IVB means the cancer has spread to distant lymph nodes
or distant organs
.
For Bile Duct Cancer
Stage I means the cancer invades the duct linings
only (inner "mucosa" or middle
"muscularis")
Stage II means the cancer invades the immediate area outside a muscular lining
.
Stage III means the cancer invades local lymph nodes
.
Stage IVA means a cancer invades nearby organs
(e.g. pancreas, liver, stomach,
small bowel, colon, gallbladder) and may also invade lymph nodes
.
Stage IVB means the cancer has spread to distant organs
(i.e. lung, liver, bone).
***The above stagings depend upon physical exam and imaging studies ("clinical staging"), and in many cases upon pathological examination of the removed ("resected") cancer
("pathological staging") . It is important to note that clinical staging alone may underestimate
the stage of the cancer.
What is the Conventional Treatment For Biliary Cancer?
Surgery has been the conventional treatment for biliary cancer. The actual surgery
performed depends upon the site and size of the tumor; as do the results. The best
results are when a gallbladder cancer is "incidentally" discovered while the
patient is having their gallbladder removed("cholecystectomy") for gallstones. These patient's often have very small cancers, and don't require
any further therapy, and are considered ed cured. On the other hand, if a patient
has a "Klatskin" tumor at the base of the liver where the bile ducts converge to
drain into the cytic duct (then into the gallbladder) then surgery to remove it is a very
major operation with large areas of liver to be removed. Even with this surgery,
the chance of surviving 5 years is less than 5% given the nature of this cancer to
have already spread prior to surgery, other therapy (called "adjuvant" treatment) such as chemotherapy and/or radiation will be necessary to increase the
chance for cure. It is important at surgery for any obstruction of bile flow to
be relieved, since it will back-up and cause jaundice if not.
"Stents" are tubes to allow bile drainage and bypass blocked areas, these don't improve survival
but make the patient much more comfortable, relieving the fatigue and itching jaundice
causes. The risks of surgery
include a death rate of 2 - 10% (depending upon the extent), an infection risk of
10%, "perioperative complications" such as heart attack, stroke, pneumonia or blood
clots totaling 10%, and bleeding or bile leakage into the abdomen after surgery (5%).
Careful surgical technique is critical to help prevent "seeding" or "spillage" of
the tumor, which makes it's chance of coming back in the local area much higher. Lymph nodes are involved in 50% patients with biliary cancers, and any suspicious nodes (larger than 1 cm) or in the area of the tumor should be
removed. Recall that the liver can regenerate and that only 10% liver function is
necessary for life, but the patient may need more liver reserve if they are to be
getting further treatment. The normal recovery time from major abdominal surgery is 3 weeks,
after which the tissues are healed to 75% of their former strength and lifting weight
is again possible. Long term digestive problems, such as loose, foul smelling stools
("steatorrhea") or difficulty gaining weight are possible after surgical manipulation
of the bile ducts. Pancreas function (digestive enzymes and blood sugar) may not
return to normal after surgery, in which case long term supplementation (i.e. insulin
injections and/or Pancrease pills) may be needed.
Radiation has been standardly used in biliary cancers, both for potentially curative and palliative
(symptom relieving) effects. Radiation treatments are prescribed by a "Radiation Oncologist", a cancer physician who specializes in administering radiation. There are 2 standard
ways of getting radiation--either as"External Beam" and "Brachytherapy". External Beam is the more common type and shines a beam of photons or electrons onto
a predesignated area of the patient's upper abdomen. Thus, it can cover a large
area of possible cancer spread. For Brachytherapy, tubes with radioactive sources are fed up into the biliary tract for a certain number
of days and then removed. Sometimes patients get both forms of radiation.
Radiation kills cancer cells by damaging their DNA, they die when they try to
divide. Thus, damaged cancer cells die even after the treatment is complete. Radiation
will also kill normal cells, which limits the amount that can be given. However,
it usually takes more radiation to kill normal cells than cancer cells, and normal cells
can often repair the radiation damage, while cancer cells can not. Nevertheless,
it is important to be as exacting as possible in the administration and dose of radiation,
so as to minimize the injury to adjacent normal cells. Particular areas of concern
when radiating the biliary tract include the liver, heart, lung, right kidney, bowel
and spinal cord. The doses to each of these areas must be carefully limited to avoid
unnecessary injury.
To receive therapy, a patient is first seen in "consult" by the radiation oncologist, who reviews the patient's medical record, complaints,
and radiology films. After explaining the possible benefits and side-effects of radiation,
the patient is scheduled for a "simulation" . This means the area to be treated is marked out on a replica treatment machine,
and films are taken. Watercolor marks are painted on the patient
to denote the treatment area, and eventually small, permanent tattoos are placed on
the skin. Sometimes the patient is sent for a CT scan along with the simulation,
the whole process takes less than 2 hours, and is painless. Information from the
simulation and relevant scans is placed into a "treatment planning computer", which generates a"plan" . This plan tells how much radiation is going to the tumor area, and how much to adjoining
normal tissues. The plan is reviewed by the radiation oncologist and also by a specially
licensed Radiation Physicist prior to starting therapy. The patient then comes in for their "treatment start" . They are placed on a hard, flat table in a specially shielded room and aligned with
laser lights. The actual treatments are given by "Radiation Therapists", or"R.T.T's", who are first certified for diagnostic X-rays and then get additional training to
deliver therapy. For the first treatment, "verification films" are taken to ensure proper positioning; they do not
tell anything about the cancer. The actual treatment only takes a couple of minutes
and is given with a "Linear Accelerator" (aka "LINAC" ), or older Cobalt-60 technology, which precisely aims a beam of photons at the treatment
area. The head of the machine can swivel about the patient, to give the treatment
from several angles. The patient needs only to lie still. Areas that are not to be
treated can be "blocked" with special lead-type blocks in the head of the treatment machine. Normally, patients
are treated 5 days a week, Monday through Friday, taking only several minutes each
day.
The usual dose of radiation for bile duct cancer with External Beam is 40 Gray (units
of radiation) given at about 2 Gray per day over 4 to 6 weeks. Often, a larger area
of the upper abdomen is treated initially, and then a "cone down" or "boost" is used to narrow the high dose treatment to the specific tumor area as seen on X-ray.
Treatment itself is painless, the patient does not
become sick, "radioactive", or lose their scalp hair from radiation to the upper
abdomen. The side effects from chest radiation for this cancer are divided into two general categories, "acute" and"late" effects."Acute" effects occur during the treatment period, and commonly resolve afterward. "Late" effects may occur months to years after treatment, and may improve very slowly or
never resolve. Typical "acute" effects are skin redness within the treatment area,
difficulty or pain on swallowing as the esophagus is treated, and general fatigue.
There may be some nausea or vomiting depending upon how much bowel is in the "radiation field",
and the daily dose given. Reducing the daily dose can help relieve nausea. Acute
reactions gradually abate after treatment is complete. Possible "late" effects include damage to the liver, which only tolerates about 30 Gray of whole
organ radiation. Smaller areas of the organ tolerate more, perhaps 45 to 55 Gray.
Whenever high dose radiation is given to a substantial portion of the liver, there
is a risk of developing"radiation hepatitis" with subsequent liver failure. This is more likely if chemotherapy is being used along
with aggressive radiation. Steroid medications may help, but severe radiation hepatitis
may be irreversible and fatal.
Another feared complication of chest radiation is spinal cord damage, since the spinal
cord is located in the spinal column closeby the common bile duct. Spinal cord damage
may be reversible, such as a temporary sensation of "electric shocks" shooting down down the body with neck flexion ("Lhermitte's sign") which is scary but commonly
resolves. Worse but very rare
with modern techniques is "transverse myelopathy", which means severing the spinal
cord from too much radiation-- this will cause permanent paralysis below the injury.
The spinal cord tolerates about 45 Gray with less than 1% chance of damage, and this
is a reason why careful "simulation" and review by a radiation physicist is crucial
to ensure that the "cord" is not being overdosed. As mentioned, this is very rare
with today's technology and training. Radiation can also cause heart damage, such
as irritation of the fluid-filled sac around the heart ("pericarditis") which may cause chest
pain and fever, and need a surgical procedure to drain excess fluid. Lung damage
may manifest as "radiation pneumonitis" if a substantial amount of lung is treated,
especially in patients who have been on steroids, long term smokers, or if chemotherapy
is also give. Since the heart and lung normally receives only a small dose of radiation
when treating for bile duct cancer, damage to those organs is very rare. Overall,
External Beam radiation is well tolerated and increases survival in compared to no
therapy.
The results of radiation for Klatskin and other bile duct tumors show an approximate
doubling of survival (from 6 to 12 months) when 40 Gray of radiation is given compared
with none
. Patients may get surgery to "debulk" the tumor followed by radiation, this approach
has increased average survival from 8 months with surgery alone to 19 months when
"post-operative" radiation is given.
Brachytherapy has been used for both primary radiation treatment and also for giving "extra" radiation
called a"boost" just to the local area of the tumor. Brachytherapy is capable of giving a very high
dose closeby it's radiation source, and minimal dose just a few inches away. This
helps spare nearby normal tissue, but does not give nearly as broad coverage as External
Beam treatment. A "catheter" tube can be surgically implanted into the bile ducts at
the time a draining stent is placed, and this tube is led out through the skin of
the abdomen ("externalized"). Radioactive sources (Cesium-137 or Iridium-192 wire)
are placed into the catheter and moved up into the bile ducts; they can remain in place for
several days to give 20 to 30 Gray (while the patient is hospitalized in a special
room). The sources are then removed and the patient goes home. In some studies the survival has been increased with this boost (from 7 to 15 months)
while in others it hasn't made any difference.
What is clear is that regular external beam treatment is necessary for all patients
getting radiation therapy, since survival was just 4 months for patients who got
brachytherapy alone compared with 14 months when both types of radiation treatment
are given. Thus, brachytherapy alone is too likely to miss regional spread of cancer and is not recommended
. However, it makes sense to boost up the dose to the tumor area.
Chemotherapy has not been studied on large numbers of patients with biliary cancers, agents
used include5-Fluorouracil, Doxorubicin, and Cisplatin. The response rate to each of these drugs is about 18%. Unfortunately, the cancer tends
to
develop resistance to this chemotherapy, much as bacteria develop resistance to antibiotics.
Thus, the patient may have an initial "good response" just to relapse a couple months
later. Side effects of chemotherapy include anemia, infection, mouth sores, diarrhea, and baldness. Doxorubicin can cause heart and lung damage while Cisplatin
causes nerve and kidney damage. Newer therapy involves using these drugs together,
which results in response of about 35% (but the side effects are also greater). Chemotherapy alone is not curative for biliary cancer, but it may cure combined with other therapy. Both Surgery and Radiation Therapy
are local, or at best regional, treatments. Chemotherapy is the only way of treating
the entire body ("systemic treatment") to kill unrecognized cancer cells that have shed off of the main tumor and implanted
in distant areas ("micrometastasis") . It makes sense to both aggressively treat local tumor with local methods, and treat
possible distant spread when it is at it's smallest, and thus most amenable to treatment,
with chemotherapy. Using more than one treatment method together is called "multi-modality" treatment and is becoming the conventional treatment for most cancers.
Results of the Conventional Treatment:
In general, by stage: 5-year Survival
Stage I 75%
Stage II
40%
Stage III
15%
Stage IV
5%
**Cancers nearer to the gallbladder have a better survival (40%+) than cancers nearer
the liver (10%). It is important to note, when looking at survival statistics, that
they include demise from all causes (e.g. heart attack, accidents, a different cancer).
Many patients with bile duct cancer are elderly and have other ("comorbid") conditions that contribute to overall mortality. The above textbook statistics do not tell
that many live live many productive years with their cancer, by controlling it's
symptoms.
Latest, Effective Treatment for Biliary Cancer:
Fortunately, there have been significant improvements in all of the modalities used
for biliary cancer:
For surgery newer operating techniques allow more complete removals of the cancer. This is important,
as few patients live more than 5 years without a surgical resection tion. The mortality
(death rate) of surgery in this area has decreased to as low as 3%, compared with 30% in past decades. While the gallbladder is expendable, bile cancers spread
up and infiltrate the liver, and so drastic operations may be needed to remove all
the local cancer. For gallbladder cancer, it may spread down the common bile duct to invade the small bowel ("duodenum") or pancreas. Pieces of these
organs can be removed by an aggressive surgeon. While removed liver will regenerate,
pancreas and bowel do not, so keen judgment is required for such major operations.
Most drastic, the newest treatment in surgery is liver transplant. This treatment is
more successful when given in conjunction with chemotherapy and radiation treatments
and has resulted in 70% survival at 3 years for patients with cholangiocarcinoma.
Dr. Starzl at the University of Pennsylvania has been a pioneer in liver transplant, which
although drastic is much more successful today than when first developed in the 1970's.
Of course it requires a matched donor, and there is a National Tissue Bank registry, along with prioritized waiting list, for getting organs such as livers. Another option
is getting a close, well matched living relative to give a piece
of their liver, which may be sufficient to sustain the life of another when transplanted.
Most people need only 10% of their liver function to survive.
Forradiation therapy the newest approach is Intra-Operative Radiation Therapy (IORT). This is a beam of electrons that is shone on the tumor, during surgery, in a
specially equipped operating room. The advantage to this is a decreased amount of
normal tissue irradiated. The usual dose forIORT is 15 - 25 Gray, given as one single treatment. This is usually followed by further
external beam radiation treatment. The results ofIORT show up to 20% survival 2 years for patients who have non-curative resections,
with control of the disease in it's local area in 50%. Some patients will live much
longer.
Side effects of IORT include narrowing of the bile ducts, and possible liver and nerve damage, but it
is generally well tolerated. It can be added to conventional external beam treatment,
so long as maximum tissue tolerance for radiation is respected. It is offered at
University Hospitals such as M.D Anderson and the Mayo clinic.
For chemotherapy the treatment may now be given into an artery that goes directly
into the liver and delivers the drug in the vicinity of the tumor. This is called
hepatic intra-arterial infusion. The response of single conventional chemotherapy agents is only 20%, but with
hepatic artery infusion it averages 50%. A big advantage of this intra-arterial
infusion technique is that it puts higher amounts of the drug into the cancer than
could be fed through the entire bloodstream without being extremely toxic. The liver is
the organ where most chemotherapy drugs are broken down anyway, to then be excreted
out by the kidneys. When giving a drug through an arm vein, for instance, it has
to pass through all the normal body areas before getting cleared by the liver. The idea of
intra-arterial therapy has been used for other cancers, successfully. Thus, it is
targeting the chemotherapy toward the cancer. The disadvantage is that it requires
a small surgery to get a catheter into the hepatic artery ("canulation") to feed the drug
to the tumor. This can be done under "fluorscopic guidance" in a radiology suite
by an interventional radiologist. The usual drug administered is 5-FU, which has been show to have good activity in many bowel cancers. Overall, for a gallbladder cancer confined to the inner lining ("mucosa")
the response rate is over 60%, but if it extends through the outer lining ("serosa")
or up into the liver, it is less than half of that. The most effective treatment ( Reported by Dr. Todoroki in Japan) for stage IV cancer of the gallbladder is using
30 Gray of IORT, combined with 36 Gray of external beam and radiation, and then adding
chemotherapy. This led to long-term survival in some of their patients, compared
to none for just surgery alone. For cancer of the bile ducts, (Reported by Dr. Fields at
Washington University in St. Louis) survival is best increased (roughly doubled)
by combination of external beam radiation and brachytherapy. It is critical for
the patient with bile-duct or gallbladder cancer to be seen by a radiation oncologist!
Using"monoclonal antibodies", that is specially designed antibodies to find find and connect to the cancer, has
been useful for detecting spread of the cancer when the monoclonals are linked
to a radioactive substance which can be scanned for. The
future idea is to put packages of strong chemotherapy or radiation on these monoclonal antibodies to target them to the cancer, but so far this approach has disappointed an not lived up to it's original expectations
.
Ultimately, gene therapy where a message is packaged in a virus to tell the
cancer
cells to "turn off" may be the cure for cancer, but we do not yet have the technology
for
this. When we do, we will be able to cure AIDS, genetic diseases and change the look
(i.e. eye color) of unborn babies as well as affect cancers. Obviously, this therapy
will
bring many new questions along with it's answers!
What about Advanced Bile Duct Cancer?
It must be recognized that many patients have biliary cancer beyond cure with
our current technology. While hope must never be abandoned, it is appropriate to
make the patient as symptom-free as possible. When bile duct cancer is stage IV,
the most advanced type with distant disease spread through the body, the objective is no
longer cure but palliation (meaning relief of pain and other symptoms). The patient should be made as comfortable
as possible, and narcotic medicines like morphine (which Osler called "G-d's own
medicine) should never be withheld for fear of causing "addiction". A convenient way of getting narcotic
relief is "Fentanyl Patches" which apply to the skin and give relatively constant
levels of the drug, mitigating the "highs and lows" common with narcotics. They are
also less likely to be "appropriated" by other people seeking narcotics. While narcotic medicines
provide necessary pain relief in over 75% of patients, they do not work for everyone.
A celiac plexus nerve block is where alcohol or phenol is placed under radiologic guidance into a bundle of nerves
in the abdomen which sense pain signals from the pancreas. It's safe and effective,
but last for about 6 months and so may need to be repeated.
Importantly, Radiation Treatment can help relieve abdominal pain, bone pain,
digestive obstruction and vomiting up of blood in up to 90% of patients. It is also
useful for reducing the symptoms, and even extending survival, in patients with spread to the brain. Sometimes radiation therapy is used as an emergency measure when
the cancer spreads to the spinal column and threatens to cause paralysis by pressing
upon the spinal cord. Any patient with biliary cancer who experiences new weakness of the extremities, numbness,
or loss of bowel or bladder function must be brought into the Emergency Room immediately
to see whether the tumor is compressing the spinal cord causing these symptoms
. Up to 60% of new back pain in a cancer patient is caused by spread of cancer there.
The patient is given a painless Magnetic Resonance Imaging (MRI) scan to check for
"epidural spinal cord compression". If this is caught early, and treatment is given,
permanent paralysis may be prevented. It is unfortunately uncommon to reverse symptoms
of paralysis once they have set it, however, so quick recognition is essential
As mentioned, radiation treatment can be very helpful for metastatic bile duct
cancer. A relatively new method of radiation for spread to thebrain is "Stereotactic Radiosurgery", where multiple beams of convergent radiation are aimed onto the area(s) of spread
in brain, in a single painless session of one afternoon. This is usually followed
by 10 to 20 sessions of conventional External Beam Radiation. The advantage of Stereotactic Radiosurgery is that it can give a very high dose of radiation to areas of brain
metastasis, and possibly enhance survival for these patients, without the risk of
an open brain surgery from a neurosurgeon.
If the bile duct area has had maximal radiation, and is still obstructed,
a "stent" tube may be put in to bypass the tumor and allow the liver to drain. This can help
relieve jaundice and itching ("pruritis"), improve digestion, and generally feel
better.
Conclusions:
The patient with newly diagnosed biliary cancer should not rely on any
one therapy, such as a pill or ray, but instead should use a combination approach
to maximize the chance for success. Specifically, besides the conventional medical
therapies mentioned above, consider the use of a non-toxic, not over-expensive alternative
therapy that you believe in, a program of spiritual renewal, "mind over cancer',
nutritional therapy and exercise. Keep the most positive attitude possible-- research
has shown this to be an important factor in survival. Using a true "multi-modality" approach will give the confidence that you have done everything possible for a happy
outcome, and certainly improve the current quality of life. CancerAnswers has a transcript on reasonable alternative therapies available through
mail or our web site
. If cure is the objective, consider getting treatments at a University Academic Center
and joining ongoing research trials which offer the latest therapies. The National
Cancer Institute has a list of open research trials on it's website, they change
periodically. Understand that particular trials are only offered at particular institutions
and patients must meet the "entrance criteria" to enroll. Also, by joining a trial
the patient may be giving up their choice for the most effective therapy. However,
new treatments give new and better hope to biliary cancer patients than ever before!
Overall, there is more hope than ever before for the patient with gallbladder
or bile duct cancer who wishes to be aggressive with treatment. Whatever the therapy
selected , it is advisable to combine it with a solid nutritional, exercise, emotional, and spiritual approach to maximize the chance of success.
This is the full transcript, offered freely in the spirit of internet sharing, of CancerAnswers' report on Gallbladder Cancer. Much more, including latest additional treatments for Gallbladder Cancer can be found on our order page. Thank you for using CancerAnswers as your information resource.
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ADDITIONAL TOPICS
Acute Leukemia
Anal Cancer
Bladder Cancer
Bone Cancer
Brain Cancer
Breast Cancer: Early
Breast Cancer: Advanced
Cartilage Cancer
Cervical Cancer
Chronic Leukemia
Colo-rectal Cancer
Esophagus Cancer
Fat Cancer
Gall-Bladder Cancer
Hodgkin's disease
Kidney Cancer
Larynx Cancer
Liver Cancer
Lung Cancer
Lung "small cell" Cancer
Lymphoma
Melanoma
Mesothelioma
Mouth Cancer
Multiple Myeloma
Muscle Cancer
Muscle and Fat Tumors
Nasal Cavity Cancer
Nasopharynx Cancer
Ovarian Cancer
Pancreas Cancer
Penile Cancer
Plasmacytomia
Prostate Cancer
Skin Cancer
Stomach Cancer
Testicle Cancer
Thyroid Cancer
Tongue Base and Tonsil
Cancer of Unknown Origin
Uterine Cancer
Vaginal Cancer
Vulvar Cancer
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