What is the Pancreas?

The pancreas is a digestive organ attached to the small intestine. It literally means "all meat" since it looks like a piece of beef. It is about 4 inches long, and has a thicker "head" portion near where it connects to the small intestine, and a thinner "tail" which meets the spleen. The area between the head and tail is called the "body" of the pan-creas.

The pancreas assists digestion in two ways. The first is it's"endocrine" activity which means that it makes hormones secreted into the bloodstream. A hormone is a chemical messenger which controls some activity distantly from where it is secreted. The most important hormones of the pancreas areinsulin and glucagon. Insulin lowers the blood sugar by causing the body's cells to uptake sugar from the bloodstream. It also allows the sugars to be stored and turned into fats. A lack of insulin, or the body's cells being insensitive to it, leads to high blood sugar ("diabetes"). Chronically high blood sugar damages the kidneys, nerves and eyes ("triopathy"). Glucagon has just the opposite effect, it causes sugars to be released into the bloodstream from the cells to raise the blood sugar, and breaks down fat to be used for energy. This is crucial to prevent the blood sugar from becoming to low, since the brain is dependent upon sugar to remain conscious. Thus, both high blood sugar ("hyperglycemia") and low blood sugar ("hypoglycemia") are harmful, and should be immediately corrected by a properly functioning pancreas.

Secondly, the pancreas has "exocrine" activity meaning that it makes substances which are excreted directly into the small intestine, through the "pancreatic duct". This duct meets with the common bile duct from the gallbladder, which also excretes important substances to assist digestion by breaking down ("emulsifying") fats. The area where these ducts meet is called the "Ampulla of Vater". Exocrine substances from the pancreas includeenzymes, such as amylase and lipase, which break down complex sugars and fats into simpler forms allowing them to be easily digested. It also makesbicarbonate to help neutralize the hydrochloric acid produced by the stomach. All these chemicals are essential for digestion, both within the intestines and even within all the body's billions of cells. A person cannot live without these activities, either from the pancreas itself or by giving replacement drugs. Fortunately, we are now able to replace enough of the pancreas' function to keep a person alive without a pancreas!

Since the pancreas is a major digestive organ, it has a very important place in the central upper portion of the abdomen, surrounded by the stomach, liver, spleen and small intestine. It receives blood from a major arterial trunk ("celiac") off of the body's main artery, the aorta. It shares both its blood supply and it's venous drainage with the small intestine, liver and spleen. Also, a separate system of tiny "lymph channels" drain blood serum from the pancreas, filtering it in nearby "lymph nodes" to purify it. Lymph nodes contain clusters of white blood cells to kill germs. The lymph nodes are connected to each other via elaborate channels, which ultimately return the purified serum to the bloodstream. Lymph nodes are normally pea-sized, but can swell up ("lymphadenopathy") when exposed to germs or cancer cells. The pancreas can becomes inflamed from backup of it's products owing to duct blockage by a bile-stone ("gallstone ileus"), by viruses or bacteria, or by excessive alcoholic beverage consumption. To say the pancreas is inflamed does not specify it's cause, but is generally called "pancreatitis" . Both acute and chronic forms of pancreatis exist, and the disease is made known by abdominal pain, digestive problems, and failure of the pancreas to perform its exocrine and endocrine functions. Pancreatitis is the most common problem with the organ. More rarely, the pancreas can be afflicted by cancer.

What is Pancreas Cancer?

Like all organs, the pancreas is made up of individual living cells. These cells are joined to form the "tissues" of the pancreas. There are several different types of cells in the pancreas to accomplish it's functions. The these cells divided rapidly while the pancreas was growing in the womb, childhood and through puberty. As adults, they only divide rarely to replace old, dying cells or injured ones. Cell division is normally under very tight control by the genetic material ("genes") inside each cell. Pancreas cancer begins in a single cell. A change occurs in the genes of this cell, which loses it's controls to prevent haphazard division. The abnormal cell starts dividing rapidly, makes millions and billions of copies of itself. Soon a clump of abnormal cells is produced, called a"tumor". A tumor simply means a swelling, and is not necessarily cancerous. When the cells in the tumor just grow in their local area, and don't ever spread elsewhere, then the tumor is "benign". However, when the tumor's cells, which are dividing out of control, have the capacity to spread to distant body areas, this is a"malignant" whichis cancer . Malignant tumors can spread to any area of the body, the process of distant spread is called metastasis. The cancer at first grows in it's local area and interferes with the pancreas' functions. When cancer metastasizes, it can grow in vital organs, cause symptoms there, and eventually kill the patient.

How Common is Pancreas Cancer?

There were about 27,500 new cases of Pancreas Cancer in the U.S.A. in 1996, and 26,000 deaths. It is the 2nd most common gastrointestinal cancer after colo-rectal cancer. Pancreas cancer accounts for 2% of the new cancers each year in the U.S.A. and 5% of cancer deaths. Men and Women are equally affected, and the average patient is 65 years old. It is rare (<1%) in patients under 45 years old. Black individuals are affected almost twice as commonly as Whites. The number of new patients per year in the U.S.A. has remained steady over the past 25 years.

What Causes or Increases the Risk for Pancreas Cancer?

No one knows why any particular person gets pancreas cancer and another does not. However, certain things have been shown to increase the risk of getting it:

1. Cigarette smoking is a factor in over 1/2 of deaths from pancreas cancer. The risk gradually returns to normal after quitting smoking for 5 years.
2. Alcoholism can cause pancreatitis ( inflammation) which is strongly connected to pancreas cancer.
3. Chronic Inflammation of the pancreas from any source, including a blocked pancreatic duct, hereditary pancreatitis, or viruses increase cancer risk.
4. Carcinogens are chemicals that increase cancer risk. Workers in coke plants or those exposure to naptha or benzene get more pancreas cancer. The DDT pesticide is linked to a 7 times increase in pancreas cancer risk.
5. Diet is linked to many gastrointestinal cancers. High fat, low fiber diets may increase risk of pancreas cancer. Caffeine has not been proven to increase risk.
6. Diabetes is weakly linked to pancreas cancer, but pancreas cancer can also cause diabetes.
7. Surgery which has removed part or all of the stomach ("gastrectomy") raises the risk of pancreas cancer by 5 times over the following 20 years.

Pancreas Cancer is not normally hereditary and is not contagious .

As you can see, something that most of the above "risk factors" have in common is that they stimulate the growth of pancreas cells through irritation or injury. The more often cells divide, the higher the chance that a mistake will occur in their genetic code (a "gene mutation") leading to a "transformed" cell which is cancerous.

Can Pancreas Cancer Be Prevented?

While pancreas cancer cannot be entirely prevented, the risk to get it may be lowered by avoiding cigarettes, using alcohol only in moderation, and lowering dietary fat. There is some evidence that vitamins "A" and"E", found in fresh vegetables and fruits, lowers the risk for all "gastro-intestinal" cancers. Interestingly, getting one's tonsils removed ("tonsillectomy") appears protective against pancreas cancer.

What are the Symptoms of Pancreas Cancer?

The symptoms of pancreas cancer depend upon where the pancreas it starts. In the tail of the pancreas, the tumor can grow very large with no symptoms at all until it spreads. In the "head" of the pancreas, closer to the small intestine, it is usual to see some jaundice (below) as the cancer closes off bile ducts. The most common symptoms for cancer in the head or body include:

1. Weight loss and decreased appetitein 3/4 of patients.
2. Abdominal pain in 2/3 of patients. This pain is gnawing, and may be relieved by leaning forward. In general, it radiates to the patient's back.
3. Jaundice means a yellowing of the whites of the eyes, then the skin, caused by backup of bile into the bloodstream. The gall bladder and the pancreas empty into the same area of the small intestine, so a pancreas tumor can block-up the bile drainage and force it to backwash into the blood. The yellow-green bile causes the yellowing of the patient, in 1/2 of these cancer patients.
4. Bleeding into the intestines is seen in about 1/3 of patients. This may be seen as thick, tarry stools (also see below), since blood released into the upper intestine will appear black ("melena") by the time it passes through the anus.
5. Itching ("pruritis") especially in the palms and soles shows advanced cancer. The pruritis usually goes along with jaundice, from buildup of blood "bilirubin".
6. Diabetes is caused by loss of the pancreas' ability to secrete insulin.
7. Loose, smelly stools ("steatorrhea") is caused by loss of the pancreas' ability to excrete the enzymes (amylase and lipase) necessary for proper digestion.
8. Liver Symptoms (right upper abdomen pain) from liver spread and swelling it.
9. Hoarsenes s is found in one-quarter of patients.
10. Paraneoplastic syndromes means unusual conditions caused by the cancer releasing (or causing to be released) chemicals. For instance, skin color may start darkening, fat in the body decomposing or shifting location, blood clots may form, new hair may develop, are arthritis may set in - all due to cancer.
11. Depression, unexplained for other reasons, may herald pancreas cancer. It is critical for a psychiatrist to realize that new onset depression, especially in the older patient, may presage cancer.

Any of the above symptoms are much more likely to represent a benign condition than pancreas cancer. Nevertheless, they should not be ignored but brought to medical attention - if it is cancer, then early detection is crucial .

What are the types of Pancreas Cancer?

The most common type of pancreas cancer by far is adenocarcinoma (95% of cases) which comes from the glands of the pancreas. About 2/3 of these occur in the head and body of the pancreas, and 1/3 in it's tail. While there are several subtypes of adenocarcinoma (i.e. clear cell, mucinous, giant cell, adenosquamous) only two subtypes make an actual difference in survival. One is "anaplastic" adenocarcinoma, more likely to occur in the body or tail; it is highly aggressive, The other subtype is cystadenocarcinoma which is more curable than regular adenocarcinoma; it may remain non-aggressive ("indolent") for many years. Other rare types of pancreas cancer include lymphoma (from the pancreas immune cells), sarcomas (from the soft tissue of the pancreas) and hormone secreting tumors ("insulinoma" or "glucagonoma" ), that are often benign but cause blood sugar problems.

It is crucial to note that only 1/4 of tumors found in the pancreas are "primary pancreas cancer" - the other 3/4 have started elsewhere (i.e. breast, lung, skin) and have metastasized to the pancreas . In fact, the origin of a tumor found in the pancreas may never become known ("cancer of unknown origin"). Thus, it is important to look for cancers starting elsewhere in the body when a new "pancreas cancer" is found.

How is Pancreas Cancer Detected and Evaluated?

There is no routine or screening test just for pancreas cancer . If a patient comes to the doctor with symptoms suspicious for pancreas cancer, the following are done:

Complete History and Physical - Many conditions can cause the abdominalpain, jaundice and depression seen in pancreas cancer, including simple pancreatitis, gallstones and viruses. These are all more common than a pancreas cancer. However, early diagnosis is essential to cure pancreas
cancer so prompt evaluation to "rule it out" is mandatory. Abdominal exam includes feeling for masses lying underneath the low part of the breast-bone and detecting gallbladder, liver, or spleen enlargement. The area around the navel and flanks is checked for skin darkening which can indicate pancreas problems. The lymph glands in the armpit ("axilla"), above the collarbone ("supraclavicular"), in the navel and groin ("inguinal") are checked for any enlargement ("lymphadenopathy"). The white of the eyes ("sclera") are checked for yellowing ("jaundice"). The quality of the voice is checked for hoarseness, and the mouth for dryness ("xerostomia") often seen with pancreas disease. Signs of recent weight loss, cough, fever and swallowing problems are checked for. Since most cancers in the pancreas originated elsewhere and spread to the pancreas, complete exam of the skin, rectum, breasts and pelvis in women, and prostate in men is appropriate.

Blood and Urine Tests are standard pre-operative ones to assess general health; there are no special blood tests ("tumor markers") yet to detect spread of adenocarcinoma as there are for some other cancers. Routine tests include Complete Blood Count("CBC") to look for anemia and infection. A Blood Chemistry Panel ("SMA") measures sodium, potassium, blood sugar, cholesterol and liver and kidney function. Some pancreas cancers cause blood calcium to be elevated and phosphorus to be lowered, these are part or the panel. Very important special blood enzyme tests for pancreas function are amylase and lipase. These will be high in acute pancreatitis, and in most pancreatic cancer where the ducts are being blocked. On the other hand, they may be low in chronic pancreatitis since the pancreas is "burned out" and will not produce it's proper enzymes. If a major surgery is contemplated, blood tests for clotting ability (PT, PTT and bleeding time ) are standard. Urinalysis (UA) to check for protein, blood or infection is routine. While Carcino-Embryonic Antigen (CEA) or CA 19-9 blood tests may be elevated in 40% of patients with pancreas cancer, they are not specific for this condition. Thus, they would not make good screening tests. However, if they are elevated, they may be used a marker for successful treatment.

Radiology Tests include plainChest X-ray which may show tumors over about 1/2 inch, signs of infection, and signs of lung obstruction or collapse. Failure to see anything on plain X-ray does not rule out spread to lung, but says that the cancer, if present, is small. A chest X-ray may miss a small tumor hidden by a rib or the silhouette of the heart. More accurate is a CT scan of the chest, which can detect tumors over about 1 cm. in any chest location. CT scan can also pick up enlarged lymph nodes in the mediastinum (middle of the chest). Lymph nodes larger than 1 cm. are suspicious; those over 2 cm. certainly have something wrong with them (infection and/or cancer). If a CT scan is given with "contrast dye" (injected into an arm vein) it helps highlight the blood vessels and is somewhat more accurate. It is worthwhile to insist on"omnipaque" dye or equivalent, it is more expensive but also more comfortable and less likely to cause an allergic reaction or kidney problems. CT scan is also used for the abdomen to demonstrate a tumor in the pancreas, it's excellent for showing spread to the liver, or to the adrenal glands above each kidney. Ultrasound used to be the first test to look for masses in the pancreas or liver, it is painless and uses sound waves that distinguish fluid from solid tissue. However, it very "operator dependent" (it's accuracy depends upon the technician) and so has mostly been replaced by CT scan of the abdomen when looking for pancreas cancer. A mass in the pancreas of at least 2 cm (about 1 inch) is seen in 95% of patients with pancreas cancer, while dilated ducts within the pancreas are seen in about 90% of patients. The test may also detect lymph glands enlarged from spread of cancer to them. Smaller tumors may still go undetected with CT scan, which is inaccurate in looking for tumors smaller than 1 cm. (about 1/2 inch).

Magnetic Resonance Imaging ("MRI") is a newer method that uses magnetism instead of radiation, it is great for looking at soft tissues in the abdomen. A contrast material called "gadolinium" can be injected into an arm vein prior to MRI to increase it's accuracy. MRI costs about $1000, 3 times more than CT. Other more exotic radiology tests are only done for specific symptoms, or if the treatment is expected to change depending upon the outcome. Brain CT will be ordered if the is suspicion of spread there.. Bone Scan involves injecting some radioactive dye into a vein; the dye has a propensity to accumulate in damaged or cancerous bone areas, which are detected by a scan. It is gotten to help rule out spread to bone, especially if new bone pain is noted and surgery is contemplated. Bone Scan is much more accurate than plain X-rays of bone in picking up cancer spread, but also more time consuming, uncomfortable and expensive. Possible appropriate tests include barium swallow to check the esophagus and stomach andbarium enema to check the rectum. For women, a mammogram is routine.

Endoscopy means placing an illuminated tube down the throat, through the stomach and into the small intestine. The area where the pancreas drains in the first portion of the small intestine ("duodenum") can be examined, and dye can even be shot up into the pancreas and pictures taken. This can also be done for the common bile duct originating in the liver. This procedure's name is "ERCP" (Endoscopic Retrograde Cholangio Pancreatography). The endoscope can also be used to sample ("biopsy") any visible tumor with a special scissors it has.

Biopsy (sampling) of the tumor is the only way to absolutely prove any cancer. Either CT scan or Ultrasound can be used to guide a fine needle into the pancreas which is done in the radiology department on an outpatient basis. The biopsy material is examined by a pathologist (a physician who specializes in diagnosing disease from tissue samples). Fine-needle biopsy is conclusive for over 90% of cancer patients. If tumor has spread to the liver, this can also be biopsied with CTscan guidance. For patient's in whom the diagnosis is still uncertain, the ERCP mentioned above can be used to look directly into the pancreas. Samples of pancreatic tissue can be biopsied with the scissors on this tube, and an accurate diagnosis can be gotten 90% of the time. Sometimes an angiography is ordered, which can help tell if the tumor can be removed surgically. For this test some contrast dye is placed into the patient's veins, and special pictures of the pancreas area are taken to visualize it's blood supply, which may be distorted by a cancer. If all else fails to diagnose suspected pancreas cancer, a laparoscopy may be performed, which is a small surgical operation to examine the pancreas via a hole made in the abdomen, or even an open-biopsy where the patient is surgically explored under general anesthesia may be appropriate.

However the biopsy material is obtained, it is sent to a "pathologist" ( a doctor who specializes in the diagnosis of disease from tissue samples). The pathologist stains the sample and determines it's organ of origin from appearance under the microscope. S(he) determines if it is cancerous by observing how frequently the cells divide, how their centers ("nuclei") look, and whether they are invading neighboring tissue. If it is cancerous, the pathologist states what type it is and how aggressive it appears. It usually takes several days of (anxious) waiting for the pathologist's report to deny or confirm cancer.

How is the Extent of Pancreas Cancer Gauged?

As for other cancers, the extent of pancreas cancer is given by the "stage" . These
stages were developed by the American Joint Cancer Committee (AJCC) :

"Stage I" means the cancer is within the pancreas or the nearby bowel or stomach, but can still be surgically removed.
"Stage II" means the cancer has extended to further areas in the abdomen, and cannot be surgically removed.
"Stage III" means the local lymph glands are involved by cancer.
"Stage IV" means the cancer has spread to other major organs or distant sites like liver, bone, lung or brain .

How Does Pancreas Cancer Spread?

As mentioned, pancreas cancer starts in a single abnormal cell. That cell ultimately makes millions of copies of itself, forming a "tumor" clump. These cells erode into the normal tissues of the pancreas, and block ducts, eventually interfering with drainage. The cancer cells get into the draining lymph channels, and are carried to lymph nodes around the pancreas ("lymphogenous metastasis") . These lymph nodes enlarge when invaded by cancer cells. The cells also get into small blood drainage channels ("venules") which carry them to both local and distant organs("hematogenous metastasis") . The original cancer within the pancreas ("primary site") can continue to grow, penetrate the wall of the pancreas, and invade nearby organs (liver, spleen, bowel, stomach, spinal column, kidney) - this is called "local or regional spread" . Meanwhile, the cancer cells that shed off into the bloodstream to be transported to distant organs implant there ("micrometastasis") and grow into large tumors. Pancreas cancer has a predilection to spread to liver, lung bone, brain, and rectum.

How Curable is Pancreas Cancer?

Unfortunately, pancreas cancer remains one the of hardest cancers to cure, in part because it is an aggressive malignancy that spreads very rapidly. If the tumor can be completely removed at surgery (stage I) then historic survival has been about 15% For more extensive cancers, only about 2% of patients have survived for 5 years. The results have been better for patients with cystadenocarcinoma, those with cancers of the endocrine pancreas (i.e. insulinoma, glucagonoma, vipoma) and those with cancer of the ampulla of Vater. These patients survival averages 40% or better at 5 years, but they represent only 10% of patients with pancreas cancer. It is important to note that cancer survival statistics include death from all causes (i.e. heart attacks, accidents, a different cancer) and many cancer patients are elderly and have other ("comorbid") medical conditions. Furthermore, newer approaches are improving survival in pancreas cancer. Moreover, it is important to remember that many patients live much longer than expected with any cancer, and that no doctor can say precisely how long any patient is expected to live. We are M.D.'s, not M.Dieties!

What is the Conventional Treatment for Pancreas Cancer?

Surgery is the historic treatment for pancreas cancer. This surgery may be either curative or palliative (symptom relieving) in intent. For curative surgery, the standard operation is theWhipple procedure. In this drastic operation, a large part of the pancreas is removed, along with a section of the small intestine and the bottom portion of the stomach. The stomach is sewn back onto the remaining small bowel. While 40% of patients used to die from complications of the Whipple (infection, leak- age, diabetes) the death rate from the operation has decreased to 10% . Only about 20% of patients with the most common type of pancreatic cancer are eligible for the Whipple, (meaning their cancer is "resectable") and 15% of these survive for 5 years. Some reasons for patients being inoperable ("unresectable") include stomach, liver or large bowel invasion, "encasement" of major blood vessels (i.e. mesenteric vein), or distant spread . Careful pre-operative evaluation has reduced the chance for inappropriate surgery from 30% to 5%, upping the "resectability rate" from 5% to 20%.

Aside from the mortality risk with major surgery, there is also the complication risk ("morbidity") of infection (10%), pneumonia, heart attack, stroke or blood clots (10%), wound breakage ("dehiscence") 5%, and the risk of not being able to resect the cancer. The outcome is better, and the complication rate less, if the surgery is done is a Major University Academic Hospital where it is performed frequently. The recovery time from major abdominal surgery averages three weeks, after which the tissue are 75% of their normal strength, and lifting weight is again possible. Since part of the pancreas is removed at Whipple, the patient will forever need to take enzyme pills ("Pancrease") for proper digestion. They may be diabetic and require close blood sugar monitoring and insulin injections (depending upon how much of the pancreas was removed). Alternatively, the patient may get an operation to palliate the symptoms of pancreas cancer. A stent tube can be placed in drainage ducts to relieve jaundice and itching, or a tumor may be removed to relieve blockage of the bowel. These operations do not improve survival, which averages just 6 months, but do make the patient comfortable.

Radiation Therapy to the pancreas has been used for patients who are "unresectable" or could not tolerate surgery, to shrink the tumor and relieve jaundice and pain. 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 pancreas include the liver, stomach, 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 a "radiation oncologist",
a cancer physician who specializes in administering radiation. S(he) 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 pancreas cancer is ~60 Gray (units of radiation) given at about 2 Gray per day over 5 to 7 weeks. Often, a larger area of the chest 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 "radioactive", have holes burned in them, or lose their scalp hair from radiation to the abdomen. The side effects from pancreatic irradiation 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 include some nausea, vomiting, skin redness and fatigue, but these resolve after treatment. Late effects are more worrisome, since if they manifest they are often permanent. Rare later effects (months to years later) are principally intestinal obstruction, stomach bleeding, liver damage and spinal cord damage; modern radiation techniques make these serious problems rare (<5%). Breaking the treatments into many"fractions" (instead of giving it all at one time) helps reduce the chance of late effects. In general, radiation alone is well tolerated, helps symptoms, but is extremely unlikely to cure the cancer. CancerAnswers offers an In-Depth Transcript on "Understanding Radiation Therapy" available through our Web Site.

Chemotherapy alone has likewise been disappointing when used alone, or after surgery, for curing pancreas cancer. Drugs used include 5-Fluorouracil (5-FU ), Adriamycin, Streptazotocin and Mitomycin-C . When used alone, about 20% of cancers show some response, but this is usually temporary. When used in combination (several drugs together) response is about 35%, but this is also short-lived. Pancreas cancer quickly develops resistance to chemotherapy, much like bacteria develop resistance to antibiotics. Chemotherapy has side effects of anemia, infections, hair loss and mouth sores. Blood counts and must be carefully monitored during chemotherapy, and any fevers promptly evaluated. Unfortunately, current chemotherapy isnot curative when used alone, but can help alleviate symptoms .

Latest Effective Treatment for Pancreas Cancer:

Recent approaches involve combining the conventional treatments to get better results than using any single method alone. There have been continuing improvements in surgery so that about 1/4 of patients can go to surgery for complete removal of their tumor. If CT scan, angiography and laparoscopy (putting in a tube through a small incision in the abdomen and looking around) all show the tumor is operable, the chance of successful operation is over 80%. A crucial factor for long term survival is whether the lymph nodes are involved; if they are not the survival with the Whipple approaches 50% at 5 years. Unfortunately, very extensive removing of lymph nodes in the abdomen("lymphadenectomy") done is Japan have not improved survival. Nevertheless, obviously enlarged lymph nodes should be removed at surgery. An important surgical advancement is the"Modified Whipple" where the pyloris (lower portion of the stomach) is spared. This has led to less problems with stomach emptying ("gastrectomy syndrome") and suture breakdown. Over 90% of patients who die of pancreas cancer will have some element of failure around the area of the pancreas ("local failure"), and since radiation treats the local area, it should help prevent failures. On the other hand, most patients who die of pancreas cancer also have spread of the disease to distant areas, which will only be helped by chemotherapy which travels all over the body. Thus it makes sense to combine treatment for both the local area, such as surgery and radiation, in addition to the most effective chemotherapy.

The Gastro-Intestinal Study Group (GITSG) has done studies showing that in patients who have had a complete surgery, adding adjuvant (additional) therapy with 5-Fluorouracil combined with radiation to 40 Gray (units of radiation) doubled average survival from 11 months to 21 months. Using this strategy, the GITSG has found that 40% of these patients survive 2 years, while 20% live at least 5 years. For the 75% of patients who cannot have curative surgery, using the same treatment with 5-FU and 40 Gray of radiation doubles average survival from 5 months to 10 months, and produces occasional cures . It is also very helpful for relieving cancer symptoms.

Another approach is to use radiation prior to surgery ("pre-operative radiation") to try to convert unremovable cancers to resectable ones . It appears to convert about 40% of patients to allow resection, and over 30% of these will survive for 5 years! In the past, patients who were "unresectable" when they first came to medical attention were simply made comfortable, in the belief that death was inevitable. Now this attitude has changed - "pre-operative chemoradiation" can shrink the tumor, allowing for surgical resection in nearly 50% of patients. If all of the apparent tumor is then removed at surgery ("negative margins of resection") then 60% of these patients are alive 2 years later. This is a big improvement over the past average survival of only 6 months for these "unresectable" patients! In addition, radiation can also be used during the time of operation when the abdominal organs are exposed. This treatment, given with a beam of electrons in a special operating suite, is called "Intra-Operative Radiation Therapy" or IORT for short. In studies at the Mayo Clinic and Massachusetts General Hospital, 2-year survival was as high as 66% using IORT . However, not all studies show a survival improvement with IORT (i.e. RTOG 8508). The main area of failure with this treatment is in the liver or abdominal cavity, for which improved chemotherapy is necessary. IORT appears to up survival with liver or stomach spread.

If a local institution does not have IORT facilities, the benefit of directly targeted ra- diation may be gotten if the surgeon places radioactive seeds of Iodine-125 into the tumor area. This lowers the cancer coming back in the pancreas (but not other) areas.

Unfortunately, using exotic forms of radiation such as neutron beams, helium or heavy-ion beams have not improved survivals compared to conventional photon treatments which are available in many hundreds of oncology facilities. These beams are very expensive, and actually increase the side-effects of radiation treatments, without any proven superiority. This was shown in part in the TAMVEC trials, where patients were treated with neutrons and photons compared to photons only, with no improvements in results. Similarly, using multiple treatments of radiation each day (hyperfractionated radiation) has not improved survival compared to conventional treatment (although it does reduce late effects and allow a higher dose to be given). Any patient with pancreas cancer who seeks life-prolongation, relief of symptoms, or possible cure should be seen by an up to date radiation oncologist! Younger radiation oncologists tend to have had more training and be aggressive than the older breed (of course there are exceptions), the field has gained much prestige in the past two decades and become much more difficult to enter and certify in. Thus, a younger radiation oncologist can be better suited to the patient who wishes to be aggressive, and is more likely to offer potentially curative "chemoradiation" in conjunction with the medical oncologist, and suggest pre-operative therapy to enhance surgical success.

How About Pancreas Cancer Spread to the Liver?

Since the pancreas is so close to the liver, and the ducts from both the liver and pancreas empty into the same place in small intestine, cancer can directly spread ("extend") from the pancreas to the liver. Also, blood from the intestinal veins is drained into the liver, which basically filters and processes all of the digestive blood. When pancreas cancer cells break off of the main tumor, they go into the bloodstream and take a route which puts them into the liver. Thus, after spread to lymph nodes, stomach and small intestine, the liver it is the most common site of spread for"locally advanced" pancreas cancer. This is considered Stage "D" or "IV" disease, but there are long-term survivors, and possibly even cures, for patients with digestive organ cancers and distant spread ONLY to the liver . Any "seed" of pancreas which gets into the bloodstream can readily get trapped in the liver, since it is a dense, fibrous organ. Once it gets trapped, it is encouraged to grow into a large tumor, since the liver has a rich blood supply and is readily expandable by a growing tumor. Usually, there are several sites of spread, or"metastasis" to the liver, and they are easily seen on a CT scan of the abdomen. These tumors can grow to very large sizes, stretch the liver capsule, and cause pain (the liver's nerves are in it's capsule). The liver is normally situated underneath the right chest ribcage. It can expand due to inflammation ("hepatitis") from an infection or having it's bile drainage blocked (by gallstones or tumor). Also, it can expand from any "infiltrative" process (something growing in the liver), such as fat cells ("steatosis"), fiber cells ("amyloid") or cancers. As the liver expands, it causes dull pain in the "right upper quadrant" (under the right ribcage) and it's edge starts poking down below the ribcage. This expansion is called "hepatomegaly" (which just means enlarged liver).

The liver is a remarkably resilient organ and only 10% of it's normal function is needed to survive. In fact part of the liver can be cut out of an adult, and it will actually regrow! This is a unique capability not seen in other human organs. The liver is an astounding laboratory sustaining metabolism. Among it's functions are purification of the blood, by detoxifying alcohol and drugs, controlling the body's sugar and cholesterol balance, making bile to digest fats, forming clotting factors for the blood and generating new blood cells. This myriad of functions makes clear why the liver is essential to life. The earliest signs of liver failure do to cancer invasion are jaundice, (seen first as a yellowing of the whites (sclera) of the eyes, easy bruising, digestive problems with fatty foods ("steatorrhea") and fatigue . With progressive liver damage, the stool turns whiter (since it is not being "emulsified" by the liver produced bile", and the patient turns yellower. Oftentimes, pain from liver capsule stretching is not seen until very large parts of the liver are involved. Ultimately, total liver failure is manifested by raising levels of ammonia in the bloodstream (since the liver normally processes off the ammonia from proteins and turns it into urea, to be excreted out of the body by the kidneys as "urine"). High levels of ammonia effect the brain, causing "hepatic encephalopathy", leading in hand flapping ("asterixis"), stupor, coma, and eventual death. Certain drugs (lactulose or neomycin) can help lower the high blood ammonia level seen with liver failure, providing temporary relief.

If there are only a few discreet "metastasis" to the liver (four or less), and the patient is medically suitable for surgery, then survival is often improved if these tumors are removed surgically, called a"metastastectomy". This is true only if the disease in the pancreas itself has been controlled ("local control"). This was demonstated in a large trial comparing surgical removal (of colon cancer spread to the liver) to "conservative therapy" (i.e. pain medicine) only. If those tumors cannot be removed surgically, then they may be shrunk by injecting ethyl alcohol into the tumors under radiographic ("fluoroscopy") guidance. Although unconfirmed in America, Japanese investigators have injected ethanol (ingestable alcohol) directly into the liver under ultrasound guidance (with a needle placed through the skin of the chest) and found a5-year survival rate of nearly 80% in patients with local liver disease only. This was even more effective than surgery for patients with operable cancers invading the liver! Also, liver tumors can be "embolized" by using gels injected into major blood vessels in the liver, this cuts off the tumors blood supply and stymies it's growth.

Radiation Therapy advances focus on delivering high dose treatment directly to the site of liver tumor. Unfortunately, the normal liver has a poor general tolerance for radiation. Also, the the nearby critical structures (lung and spinal cord) again don't tolerate high dose treatment, and this had limited the usefullnes of the conventional "Exernal Beam" treatments given in standard Radiation Therapy departments. It can provide some relief from pain from capsule streching by growing tumor, but with a dose limited to about 30 Gray cannot cure tumor spread to the liver. Also, there is usually lots of nausea and fatigue when treating large liver areas with radiation, making it very unpleasant. Futhermore, the liver can get "radiation hepatitis" from doses higher than about 25 Gray, with progressive liver failure as a result. Thus, conventional radiation is not considered a good option today for patients with spread of pancreas cancer to the liver. In fact, while irradiating the pancreas, Radiation Oncologists tend to be cautious and block as much liver out of the field as possible. However, large portions of the liver can be included with Intra-Operative Radiation Therapy, since the total dose is given at one time and a lower dose is used. Also, catheters (tubes) with radioactive sources, such as Cesium-137, can be threaded up though the liver's blood vessels, be placed closeby tumors, and left in place for a specified time to shrink them. This form of radiation is called "Brachytherapy" and is generally much better tolerated than "External Beam" therapy.

Chemotherapy has been given directly into the main artery of the liver, the "hepatic artery", to treat metastasis, and has shown some impressive shrinkage of liver tumors. Unfortunately, it has not been proven that "Hepatic Arterial Infusion" (of 5-FU) extends survival compared to conventional administration of the drug into the veins. Also,liver transplant has not been shown to increase survival for pancreas cancer.

Current experimental therapies for advanced pancreas cancer include use of the chemotherapy drug "Gemcitabine"("Gemzar") which was approved by the FDA in 1996 for advanced pancreatic cancer. There is a study at the University of Chicago using this drug sponsored by the American National Cancer Institute (NCI). Another interesting study (for colo-rectal cancer metastatic to the liver) is using the durg Flucyosine (5FC) with a "Replication Deficient Adenovirus Vector" containing the "Cytosine Deaminase Gene" - this study is being done at Cornell University in New York for patients aged 18 to 70, and combines chemotherapy with gene therapy. Another study at the Mayo Clinic in Minneapolis, Minnesota is using a Seven Day course of an oral chemotherapy drug "Ethynyluracil" along with 5-FU in patients with unresectable or metastatic digestive organ cancer, for patients aged 18 and over. This new drug is also being used at the University of Chicago along with Leukovorin calcium and 5-FU in an NCI sponsored study for advanced digestive organ cancer. There areGene Therapy protocols sponsored by the National Institute of Health for any advanced cancer, and while these have shown success in shrinking tumors they have not yet been a total cure.CancerAnswers has an available transcript on In-Depth Gene therapy available through our Website .

What About Advanced Pancreas Cancer?

It must be recognized that many patients have pancreas 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 pancreas 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". For severe pain a good option may be "Fentanyl Patches", which are placed on the skin and replaced every 3 days, they are much stronger than regular morphine and keep a more constant blood level of narcotic - helping to avoid the "highs and low" of pain relief therapy. 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 is safe and effective, but only lasts 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 stomach 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.

Radiation Treatment can be very helpful for metastatic pancreas 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 may be followed by 10 to 20 sessions of conventional External Beam Radiation. The advantage of Stereotactic Radiosurgery is that it gives a very high dose of radiation to area(s) of brain spread, and possibly enhance survival for these patients, without the risk of an open brain surgery from a neurosurgeon. If the pancreas area has had maximal radiation, and is still obstructed, a "stent" tube may be put in to bypass the tumor and allow the pancreas to drain. This can help relieve jaundice and itching ("pruritis"), improve digestion, overall helping the patient feel better. While not proven to increase survival, it helps quality of life.

The patient with newly diagnosed pancreas 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.

Again, FDA has approved Gemzar (gemcitabine) for advanced pancreatic cancer as of July 1996. It is recommended for patients with inoperable or metastatic pancreatic cancer, where it helps relieve symptoms, as well as for patients that have failed 5-FU treatment. It is the first new treatment for pancreatic cancer in a decade.

Our conclusion is that while pancreatic cancer is inarguably a very serious disease, aggressive treatment is saving more lives than ever before, and better techniques for symptom relief should at least improve quality of life for all patients.Patient's in otherwise good health owe themselves a consultation with a doctor in a University Hospital setting, affiliated with a medical school, who is familiar with current clinical trials. With today's technology, no one should suffer the full brunt of untreated pancreas cancer. The future has never looked brighter for pancreas cancer patients

This is the full transcript, offered freely in the spirit of internet sharing, of CancerAnswers' report on Pancreas Cancer. Much more, including latest additional treatments for Pancreas Cancer can be found on our order page. Thank you for using CancerAnswers as your information resource.