How and Where does the Stomach Work?

The stomach is an expandable sack located mostly under the left lung, between the muscular "diaphragm" which pushes up the lung, and the coiled small intestine. The stomach is close-by important organs in the abdomen. To it's right is the liver, to it's lower left is the spleen, and underneath it is the pancreas . The esophagus enters the stomach at the "gastro-esophageal"junction, while the small intestine exits it at the lowermost "antrum". The front of the stomach rests on the abdominal wall, and lower parts of it also contact the upper left kidney and "transverse" colon. You can see that the stomach is in the midst of many vital organs, and infections or cancers can spread to these organs. Important areas of the stomach itself (besides the antrum and gastro-esophageal junction) are the "greater curvature" (basically the left wall of the stomach), the "lesser curvature" (the right wall), the "fundus" (main body of the stomach) and the "cardia" (uppermost portion). The stomach has a delicate inner lining, made up of "columnar epithelial cells", and acid secreting cells called "parietal cells" . This lining is protected chemicals called "prostaglandins''.

The stomach has an impressive blood supply, mainly from the "celiac artery" which comes off of the main artery, the aorta . There is also venous drainage of blood to the spleen and liver. A secondary drainage system, called the "lymph system", filters the blood in normally pea-sized lymph nodes. These are connected to lymphatics in other abdominal areas by "lymph channels" . Lymph nodes are full of white blood cells that help purify the blood serum; lymph nodes often enlarge when they detect spread of diseases.The point is that the stomach's rich blood supply and many drainage paths can act as conduits for spread of infections or cancers.

Of course, the main purpose for the stomach is digestion of foods, a process that begins with the saliva in the mouth. The stomach activates Vitamin B12 from our diet, secretes hydrochloric acid to break down food, and churns the food into pulp. It can also directly absorb substances like alcohol and caffeine. The stomach is susceptible to an increase in the concentration of hydrochloric acid brought on by stress, certain foods, and the effects of tobacco smoke. While the stomach is normally protected against it's own acid by an inner membrane, breakdown of this membrane leads to inflammation of the stomach, called "gastritis" . An area that loses it's membrane is also at risk to get an actual hole, called an "ulcer" . An ulcer may be shallow, and heal quickly, or it may be very deep and even "perforate" the outer stomach wall. Perforation is a surgical emergency. Fortunately, there are many medications now available which help reduce stomach acid concentration (i.e. Zantac, Pepcid, Tagamet), helping ulcers heal and preventing formation of new ones. Also, soothing protectants (Carafate) and even artificial prostaglandins can be given. These medications are often given preventively ("prophylactically") when the body is under great stress, such as after major surgery. While most stomach problems are minor ones, such as a mild virus or indigestion, occasionally serious disease strikes the stomach.

What is Stomach Cancer?

The stomach is composed of various "cells", which are intricately combined together into "tissues"which form the "organ" . These cells divide to produce new ones, and grow very rapidly during womb life, early childhood and puberty. In adulthood, new cells are produced only to replace those that die of old age, injury or disease. Normally, division of cells is under very tight control. This control is exerted by the "genes" inside each cell, which are housed in long clumps forming "chromosomes", which are visible under a light microscope. The genes themselves are made up of DNA, the master genetic code material. If the genes are damaged, say by chemicals or radiation, the control over cell division may be lost in one particular cell. Ultimately, cancer is considered a disease of the DNA.Stomach cancer starts in a single lung cell . That cell starts dividing haphazardly, making millions and billions of copies of itself. It takes up the nourishment needed by other cells, depriving them so the cancer can continue to grow. Quickly growing cells can clump up to form a "tumor" . A tumor simply means a swelling, it can be caused by inflammation or infection. A "benign" tumor only grows in it's local area (although it may get quite large)-- it cannot spread and is not cancer. By contrast, a tumor which can spread to other body areas is called "malignant" and this is cancer . The process of cancer spread to other areas is called "metastasis", so only malignant tumors (i.e. cancer) can metastasize. Theoretically, cancer can spread to any area of the body, and it often grows better in it's area of spread than in it's area of origin ("primary site"). It is this capacity for spread that makes cancer so dangerous. If not treated successfully, it ultimately kills by debility, anemia, infection, and compromise of normal body functions.

How Common is Stomach Cancer?

Stomach cancer is the most common cancer in the world (after skin cancer). In the U.S.A. it is much less common, with 25,000 new cases per year causing 14,000 deaths. This means it is about 3% of new cancers in the U.S.A. each year. Stomach cancer has decreased 5-fold in the U.S.A. over the past 50 years. It is more common in males, extremely rare in children, and the average patient is 55 years old.

What Causes, or Increases the Risk for Stomach Cancer?

As for any cancer, the exact reason why one person gets stomach cancer and another does not remains unknown . However, several things have been noted, when looking at groups of patients, that increase cancer risk. These "risk factors" are:

Lack of Refrigeration is seen in countries with a high level of stomach cancer, as used to be the situation in the U.S.A. prior to 1940 (when cases were very high). Preservatives like nitrates, which were commonly used before refrigerators, may be contributory.

Increased Smoked and Salted Food intake appears related to stomach cancer, and may be related to lack of refrigeration in third-world countries today.

Low Fruits and Vegetables in the diet, and high fat, is related to many "aerodigestive" (mouth, throat, lungs and gastrointestinal system) cancers, possibly by depriving the body of vitamins like "A" and "E" which appear protective for cancers. On the other hand, lots of fruits and vegetables appear to lower risk.

Chemical "Carcinogens" like rubber by-products, coal tar and asbestos have increased cancers in industrial workers. However, Alcohol and Tobacco do not seem to increase stomach cancer risk.

Long Standing Ulcers, especially those on the lower curvature, may become malignant over time. A common bacteria, called Heliobacter Pylori, is found in many ulcers and may increase cancer risk over time. Overall, however, less than 2% of ulcers ever become cancerous.

Prior Stomach Surgery, where part of the stomach is removed ("partial gastrectomy") for bleeding ulcers, has about a 5% chance of stomach cancer after a "latent period" of as much as 40 years.
Achlorhydria means no stomach acid, this is seen in a rare syndrome called "achlorhydria-gastric polyposis"-- these patients have a 30% chance of getting stomach cancer. Any ulcer in a patient with no stomach acid has almost a 100% chance of being cancerous!

Rare Genetic Diseases such as Plummer-Vinson syndrome (10% lifetime risk) and Peutz-Jeghers syndrome with multiple polyps have a higher risk. Any polyps in the stomach that are "villous" (as opposed to the more common harmatomatous type) have increased risk for becoming cancerous, just like for colon cancer. However, villous polyps in the stomach are quite rare. Pernicious anemia is caused by the failure of parietal cells in the stomach to secrete the "intrinsic factor" needed by the intestine to uptake vitamin B12; then cancer risk is increased.

Race Even after equalizing all of the above factors, Orientals, Blacks and Hispanic individuals get stomach cancer more commonly than Whites. This may be due to some pre-existing genetic susceptibility to stomach cancer.

What is the Location of Stomach Cancers?

Overall, 50% are in the lower stomach ("pyloris and antrum"), 20% are in the body of the stomach ("fundus"), 20% are in the lesser curvature, 10% at the cardia, and 3% at the greater curvature. The lower stomach ("distal") is more commonly involved in Black individuals, while the upper stomach ("proximal") is more common for Whites.

What are the Symptoms of Stomach Cancer?

As for any cancer, very early stomach cancer will produce no symptoms, since the disease is too small to interfere with normal functions. When the disease gets large enough to be noticed, it is usually still some time before it comes to medical attention, since the initial symptoms are usually mild and non-specific. The average "delay to diagnosis" is 6 months. Common symptoms of stomach cancer include:

Symptoms of Stomach Cancer:

Pain in the "epigastric" area, that is below the breastbone ("sternum") where the chest joins the abdomen, is seen in 90% of patients when they first come for medical help (called "presentation"). This is the most common symptom, and the pain is usually gnawing and may radiate toward the back. It may be partly relieved by anti-acids, but gets worse over weeks to months.

Weight Loss is seen in 80% of patients, they do not feel hungry and feel full after a small intake of food ("early satiety"). Also, a growing cancer burns calories.

Anemia means lowered Red Blood Cell ("RBC") counts from either tumor bleeding, malnutrition or both. Actual vomiting up of blood ("hematemesis") is seen with cancers which erode deeply into the stomach wall. Symptoms of anemia are progressive fatigue and paleness, and black "tarry" stools.

Nausea and Vomiting appears in 50% of patients. This can be from mechanical blockage, called "obstruction", of the inlet or outlet of the stomach by a growing tumor. Projectile vomiting is characteristic for stomach outlet obstruction.

Paraneoplastic Syndromes are conditions caused either by some substance a cancer is secreting, or by the tumor itself. They are rare, but seen, in stomach cancers and include body pigment changes ("acanthosis nigricans"), walking unsteadiness ("cerebellar ataxia"), vein inflammations ("thrombophlebitis).

Symptoms of Disease Spread include bone pain, brain symptoms (memory lapse, coordination difficulties, numbness, partial paralysis, seizures), liver pain from stretching of the liver capsule from metastasis, and abdominal swelling. Lymph glands in the left armpit ("Irishes' node"), left collarbone ("Virchows node") or belly button (Sister Mary Joseph's node") may swell ("lymphadenopathy"). The disease may ultimately spread to any body area. It can cause ovarian swelling or even meningitis.

Only 1% of patients have no symptoms, with the disease found coincidentally.

What are the Types of Stomach Cancer?

This is actually two different questions. The first asks what are the types of cells, as seen under the microscope, that give rise to stomach cancer? The vast majority of stomach cancers (over 95%) areADENOCARCINOMAS, meaning that they arise from the stomach's inner lining glandular cells. Of the 5 remaining cases per 100, three will be lymphoma (arising from the stomach's immune cells), one will be leiomyosarcoma (from muscle cells) and one will be "undifferentiated" (origin not identifiable). This paper deals only with treatment for adenocarcinomas . The other rare types are dealt with in the "Non-Hodgkin's Lymphoma" and "Muscle Cancer" transcripts.

The second question is what the cancer actually looks like to the eye, that is it's "gross appearance". Three quarters of stomach cancer looks like an pit (ulcerative"), and may have a raised border. 20% grow as raised lumps along the stomach's inner lining ("polypoid"). Sometimes the entire stomach lining may be involved ("linitis plastica") causing loss of elasticity. The cancer spreads only superficially in 5% of pts.

How Does Stomach Cancer Grow and Spread?

As mentioned, stomach cancer starts in a single abnormal cell. This cell divides to make millions and billions of copies of itself, forming a tumor. A malignant tumor erodes into the lining of the stomach, and into the "submucosal" and "muscular" layers. There, it sheds cells into the lymph channels which spread to local lymph nodes, causing them to swell ("lymphadenopathy"). Cancer cells shed into the tiny draining veins of the stomach, where they can travel to the spleen, liver, bone, lung and brain. The original tumor (called the "primary site") continues to grow, it can penetrate the outer wall of the stomach to erode into the liver, kidney, pancreas or intestines. The cancer can actually encase the entire bowel by spreading via the intestinal surfaces ("peritoneal spread"). The cancer may travel up the stomach to invade the esophagus, or down to invade the small intestine ("duodenum"). As it invades nerve bundles, it causes pain. While the cancer may spread to any organ, over 90% of patients succumbing to stomach cancer have disease remaining in the stomach area ("local disease") at their time of demise.

How is Stomach Cancer Diagnosed and Evaluated?

Like any cancer, the only absolute way that stomach cancer can be diagnosed with certainty is by getting a sample piece of it, called a "BIOPSY", for examination. The biopsy material is studied under the microscope by a "Pathologist", a physician who specializes in diagnosing diseases through tissue samples. If a patient comes to their doctor with symptoms or signs suggestive of stomach cancer, the following evaluation is standardly done:

Complete History and Physical Examination with special attention to the head and neck, chest, and abdominal areas. The patient is carefully questioned about abdominal pain, nausea, and bowel movements. Signs of anemia, infection, and recent weight loss are noted. The abdomen is examined for liver and spleen swelling (hepato-splenomegaly") as are the armpits ("axilla") and area above the clavicles ("supraclavicular") for lymph node enlargement. Neurologic exam is done; the male prostate is checked, as are the pelvis and breasts in females.

Endoscopic Examination means placing a visualization tube under light local anesthesia into the nose and down the throat, into the esophagus and then into the stomach. This procedure is usually performed by a "Gastro-enterologist", a physician specializing in care of the digestive organs. Direct endoscopic visualization of the stomach is "direct gastroscopy" and is performed after first spraying some mild numbing medicine (lidocaine) into the throat to help prevent irritation and gagging. A mild mixture of demerol and valium may be used for a light ("twilight") anesthesia. The general condition of the stomach is noted, with attention to the gastro-esophageal junction, cardia, antrum, and any ulcers or tumors. A diagram is marked into the medical record to show the location of any abnormalities. A biopsy is taken of any suspicious areas, and sometimes "blind biopsies" are taken of areas most likely to develop cancer ( i.e. lesser curvature).

The endoscope can look at many areas of the head and neck, throat, lungs, and digestive system. It is appropriate to check any suspicious area, since 5% of patients will be found to have a "second primary" when they first come to medical attention-- that means another simultaneous cancer. Endoscopy is a very safe procedure, it can easily take small biopsies, and is the clearest way (besides open surgery) to actually look at tissues of the aero-digestive tract.

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 stomach adenocarcinoma as for some other cancers. Routine tests will 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. If a major surgery is contemplated, blood tests for clotting ability ( PT, PTT and bleeding time ) are standard. A Urinalysis (UA) to check for protein, blood or infection completes the lab tests.

Imaging Tests are done in the radiology department and standardly include a Chest X-ray to look for signs of infection or lung tumors. Also free air in the chest is seen if the tumor has penetrated the stomach. Barium Swallow has been the conventional test to see if there is a tumor in the stomach area, and today is still often done prior to endoscopy. The patient drinks some thick barium contrast material, and a series of X-rays are taken. Air may also be pumped into the stomach, this enhances the resolution of the test and is then called a "double contrast" study. This outlines any noticeable abnormality in the stomach or the the hollow ("lumen") of the esophagus. It will outline any ulcers and show if there is any tumor or blockage of the stomach. If there is any problem swallowing, it is CRITICAL to do a "MODIFIED" (instead of the "regular") barium swallow, since if a large quantity of barium is swallowed, it may be shunted ("aspirated") into the lungs causing chemical pneumonia. CT scan in "thin slices" of the tumor area helps define the extent of the tumor, and is excellent for looking for spread to lymph nodes around the stomach which cannot be detected on standard physical exam.

Another excellent test to study the soft tissues in the abdomen is the expensive Magnetic Resonance Imaging (MRI) scan. MRI, which uses magnetism instead of radiation, allows the area to be viewed in three dimensions. It is great for looking at the tumor as well as checking local muscle, fat and nerves for signs of invasion by cancer. Contrast material can be injected into the bloodstream prior to either CT scan or MRI, the contrast runs through and highlights blood vessels. If getting a CT with contrast, ask for "omnipaque" contrast; other types are less expensive but more likely to cause an allergic reaction. For MRI scans, a different type of contrast, called "gadolinium" is used. Other more exotic tests are only obtained in the presence of suspicious symptoms. For instance, a bone scan is gotten if there is new bone pain, a CT of the chest is ordered when the plain Chest X-ray appears to show tumor in the lung, and a CT of the Brain is gotten if new neurological symptoms occur. Certainly, other areas of the gastrointestinal tract (such as the colon and rectum) may need to be examined. If major surgery is contemplated, Lung Function Tests ("FEV") are done in the pulmonology dept. to assess lung capacity. An EKG is gotten to rule-out recent heart attack, and if heart abnormalities are suspected a stress-thallium and/or echocardiogram look at the heart. Tests can be ordered to look at any area of the body-- but only if necessary.

Biopsy (sampling) is crucial, since only by examining an actual piece of the tumor under the microscope can a diagnosis of cancer be made, and then the particular type known with certainty. For a very small tumor, the whole of it may be removed, along with a "safety margin" of surrounding normal tissue, and sent for evaluation ("Excisional Biopsy"). For a larger tumor, a cut is made into it so some tissue can be removed for examination ("Incisional Biopsy"). It usually takes several days (of anxious waiting) for the pathology report to come back.

A pathologist is a physician who specializes in diagnosing disease from tissue samples. The pathologist will confirm or deny cancer in the "biopsy specimen", and name the particular type and"grade" if cancer is found. "Grades" are given as I, II or III and indicate the probable aggressiveness of the cancer. "Grade III" is "high grade", shows rapid cell divisions, and doesn't look much like normal esophagus tissue. It is likely to be aggressive. The most aggressive type tend to be "undifferentiated" carcinomas who's cell of origin is unclear. On the other hand, "Grade I " will look a lot like the normal tissue it arose from, have relatively few cell divisions, and tend to be more "indolent" (slower to grow and spread). "Grade II" is intermediate in behavior. The pathologist may need special stains and even an electron microscope to precisely characterize the cancer; there may be more than one type of cancer or grade within a given tumor ("mixed tumor").

The only sure way of accurately gauging the extent of cancer is by surgical exploration of the abdomen ("exploratory laparotomy") --details to follow.

How is the Extent of Stomach Cancer Gauged?

As for other cancers, the extent of stomach cancer is described by the "stage" . The American Joint Cancer Committee ("AJCC") staging has become standard, and is based upon what is seen at surgery :

Stage I means the cancer may penetrate in the the stomach muscle, and local lymph glands (within 3 cm. or about 1 and 1/2 inches) may be involved.
Stage II means the cancer can penetrate through the outer lining of the stomach ("serosa") or lymph glands further than 3 cm. from the tumor are involved.
Stage III means the cancer has spread to other local organs, or penetrates the outer lining andlymph glands further than 3 cm. from tumor are involved.
Stage IV means the cancer has spread to distant organs, i.e. bone or brain.

What is the Survival with Stomach Cancer?

This depends upon many factors, such as the cancer's stage, the treatment selected, and the general condition of the patient. The survivals by stage, given in textbooks, for conventionally treated patients are:

Note that the above survivals include death from all causes in stomach cancer patients, including heart attack, accidents, other cancers, etc. Many stomach cancer patients are elderly and have other medical ("co-morbid") conditions. Furthermore, many patients live high quality lives with incurable stomach cancer, if the symptoms are properly treated ("palliation"). Moreover, as will be seen, the latest therapies appear to boost the above survival rates considerably.

What is the Conventional Treatment for Stomach Cancer?

Conventional treatments for stomach cancer include Surgery, Radiation Therapy, and Chemotherapy. The latest effective treatments have improved all of these therapies and often use them in combination, as will be seen.

Surgery has been, and remains, the main treatment for early stomach cancer. It is the only treatment absolutely proven to improve survival in stomach cancer, although new therapies appear very promising, as will be shown. Surgery involves slicing into the abdomen ("laparotomy"), determining the extent of the cancer, and removing it if possible. A steady increase in safety has meant more patients are "surgically staged" using laparotomy, whether or not curative surgery is possible. Even if curative surgery is not possible, valuable information is obtained for other therapies (i.e. tailoring radiation therapy fields). If the disease is obviously massive on CT scan or MRI, there is no point to doing laparotomy. If, however, the extent of cancer remains in doubt, it is a normal part of the"staging evaluation", (provided the patient can tolerate surgery). Moreover, it will be therapeutic if curative surgery can be done.

In the 1940's, only 30% of stomach cancers were found to be "operable" when the patient was opened at surgery. Today, improved surgical techniques now allow 60% of patients to be "operable" at surgery! The extent of surgery has been looked at carefully to determine what works best. It might seem that the more extensive ("radical") the surgery is, the better the patient will do. This is not necessarily so, since patients who get radical surgery may have more extensive disease to start with. Of patients who have their whole stomach removed ("radical gastrectomy") only 10% were alive 10 years later, while if only part of the stomach was removed ("subtotal gastrectomy") 40% were alive 10 years later! In fact, for the most radical operation, in which both the stomach and the esophagus were completely removed ("esophagogastrectomy") only 2% of those patients were alive 10 years later. Thus, the operation with the best long term survival has been Subtotal Gastrectomy.

This has become the most common surgery for stomach cancer in the United States today. The patient has the advantage of retaining some stomach, and less surgical problems. In general, there is a 3% chance of surgical death, 10% infection risk, 10% blood clot risk, and a 3 week recovery time from subtotal gastrectomy. After 3 weeks, the scar is 75% healed and lifting weight again allowable.

Another important question for the extent of surgery has been how much lymph node removal to perform. Recall that the area around the stomach is rich in draining lymph nodes, which can be a conduit for cancer spread. In fact, lymph nodes are the most common site of early spread beyond the stomach proper. In Japan, where stomach cancer is more common and often detected early, researchers have claimed that extensive removal of local lymph glands increases survival. This is called an "R3" dissection. In the U.S.A., only a lesser "R1" lymph node dissection is usually done. This is because a large study in Britain, by a Dr. Dent in 1988, showed no survival advantage to more surgery. The "R2" dissection is more extensive than the "R1" but less than the "R3" . At the Mayo Clinic, even patients who had "R2" or "R3" lymph node dissections still often had recurrence of the cancer right in the area of surgery! This shows the difficulty of doing a complete lymph gland removal in this area. At best, surgery can only be a local therapy, it does nothing for spread of disease. However, it remains the best current treatment for operable stomach cancer. The 5-year survival with surgery alone ranges from 25% for stage III to nearly 100% for stage I, especially if the lymph nodes are not involved.

Radiation Therapy alone has been used for patients who cannot tolerate surgery, or for those in whom surgery could not possibly remove all of the cancer. Radiation alone can cure a small but reproducible percentage of patients with locally advanced stomach cancer. Like surgery, radiation therapy is a local treatment, but a wider "field" may be radiated than removed surgically. As will be seen, it can be combined with other therapies to increase "local control" of stomach cancer, since return of stomach are disease has been a major problem for unsuccessfully treated patients. Radiation Therapy can also help relieve ("palliate") the symptoms caused by distant spread of the disease. Treatment is administered under a "Radiation Oncologist", a cancer doctor who specializes in utilizing 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 stomach include the liver, heart, lung and spinal cord. The doses to each of these areas must be carefully limited to avoid unnecessary injury. This is the art and science of proper treatment.

To receive therapy, a patient is first seen in "consult" by the radiation oncologist, who reviews the patients 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 alone for stomach cancer is ~60 Gray (units of radiation) given at about 2 Gray per day over 5 to 7 weeks. Lesser doses are used when simultaneous chemotherapy is given. Often, a larger area of the 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 ispainless, the patient does not become "radioactive", or lose their scalp hair from radiation to the chest. 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, nausea, diarrhea, difficulty or pain on swallowing as the esophagus is treated, and general fatigue. Possible "late"effects include damage to normal lung ("radiation pneumonitis") which causes cough, fever and shortness of breath. It only occurs in about 10% of patients and is often treatable with steroids. However, it is occasionally fatal. Treating large areas of lung, and/or giving chemotherapy along with chest radiation, increases the chance for radiation pneumonitis. Treating the liver too aggressively can inflame it ("radiation hepatitis"), which may or may not resolve with steroids, or damage to the liver's draining sinusoidal pathways ("veno-occlusive disease") which may also be fatal. Another feared complication of chest radiation is spinal cord damage, since the spinal cord is located in the spinal column behind the stomach. 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 cause later small bowel obstruction requiring surgery in about 3% of patients. . It 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. This is also very rare. Therapy can cause a big decrease in stomach acid production in 25% of patients by damaging the parietal cells which secrete hydrochloric acid. In fact, it was used for ulcer disease before better medicines became available to reduce stomach acid. Overall, conventional "External Beam" chest radiation is well tolerated, and acute side effects can be relieved by anti-acids like Zantac and anti-nauseates like compazine or Zofran. Radiation often increases survival in stomach cancer, compared to no therapy.

There is no question that local radiation is very valuable in relieving symptoms of esophageal cancer, whether from pain from spread to ribs (or other bone) or helping reduce the vomiting up of blood (hematemesis) from the cancer. It can be used to relieve neurological symptoms from spread to the brain, or dangerous pressure upon the spinal cord from metastasis. Thus, radiation therapy is almost always used in advanced cancer to relieve symptoms, with up to 90% effectiveness.

Chemotherapy alone stomach adenocarcinoma has been very disappointing, and today it is often combined with radiation therapy. From large trials at the Mayo Clinic, there is evidence thatchemotherapy combined with radiation works better than either "modality" alone. Usual chemotherapy "agents" include 5-Fluorouracil ("5-FU"), Adriamycin, and Mitomycin-C . When all these agents are combined together it is called the "FAM" regimen for short. As we have seen, surgery is only local therapy and we have historically had problems with both local disease left at surgery and distant spread of stomach cancer. Chemotherapy is "systemic" treatment, that is it circulates through the entire body. It may thus treat any unnoticed cancer cells which have shed to distant areas ("micrometastasis') . Initially, this spread will be too small to be detected by any imaging scan, and this is precisely when chemotherapy can be most effective at eradicating it.

Chemotherapy has been given after surgery to "mop up" any cancer cells that might be remaining even after apparently curative operation. In this context, chemotherapy is called "adjuvant" (meaning "extra") therapy. A combined group of American researchers, called the "Gastro-Intestinal Study Group" ("GITSG") found 60% of patients who got adjuvant chemotherapy after surgery lived at least 5 years, compared to just 45% of patients who did not get chemotherapy after surgery. This represented a 25% improvement in net survival with adjuvant chemotherapy!

Combination Therapy looked at combining all three conventional methods together. That is, patients first received surgery , then had both chemotherapy AND radiation therapy as "adjuvant" treatment. The overall conclusion was an up to 20% increase not be the most optimum way to give combination therapy, however. It is possible that survival would have been increased even more if chemotherapy and radiation therapy had been given together first, to shrink the cancer, with surgery added afterwards to remove any residual. This method has gained wide acceptance in esophagus cancer and is called "neo-adjuvant pre-operative chemo-radiation"and is being investigated.

The side-effects of chemotherapy agents, which are given into the veins, include:

1) 5-FU, the most common agent for Gastro-Intestinal cancers, lowers blood counts (remember 80% of stomach cancer patients are already anemic), and can cause mouth sores, nausea and diarrhea. It is given either as single, large doses ("bolus"), or as a sustained drip into the veins ("infusion"). Studies for cancers in other areas have shown some advantage to the infusion method.

2) Adriamycin is a bright red liquid which can cause heart and lung damage; the dose is limited to 500 mg. per square meter of patient body area (people are 1 to 2 square meters). It is routine to get a heart scan called a "MUGA" test before giving adriamycin. Lowered blood counts and hair loss ("alopecia") are expected with adriamycin. Patients get more skin redness and irritation (called a "recall reaction") if radiation is also given, even months later.

3) Mitomycin-C lowers blood counts, and causes lung and kidney damage. The lower red blood cell count leads to anemia with paleness and fatigue, and may require transfusions or injection of "erythopoeitin" (Epogen) which stimulates red blood cell counts. Lowering of the white blood cell count can lead to fever and infections called "febrile neutropenia"; white blood counts can be stimulated with "colony stimulating factors" (Neupogen). Drops in platelet counts lead to easy bruising or even internal bleeding. Platelet transfusions are given if the count drops below 20,000 to prevent massive hemorrhage. Lowering of blood counts is more severe if radiation is also given, so patients should be carefully monitored with at least weekly blood counts.

What is the Latest, Effective Treatment?

Advances in surgery, radiation and chemotherapy have improved all of these modalities. Recall that now over 60% of patients are operable, more than double that of just 40 years ago. It took studies and time to understand that more surgery is not necessarily better; that more limited procedures like "subtotal gastrectomy" and less extensive lymph node dissection patients did better than with the most aggressive surgery. Radiation improvements have included using sophisticated "conformal three-dimensional treatment planning" to maximize the dose to the tumor and minimize it to surrounding normal structures, and higher energy machines that more evenly treat the tumor area while sparing the skin and underlying muscle. Chemotherapy has advanced considerably with availability stimulating factors to correct low red and white blood cell counts, and better anti-emetics like Zofran to reduce nausea and vomiting. The idea of using combination therapies, to get the best benefits of each and extend survival, has become commonplace treatment.

One of the most exciting areas of new therapy for stomach cancer comes from the Far East. Recall that the disease is more common in Orientals, and a lot of quality
research has come from Japan. The Japanese (Kyoto Trial) and the Chinese (Beijing Trial) have found MUCH BETTER SURVIVAL in relatively advanced stomach cancer if patients are given "Intra-Operative Radiation Therapy" ("IORT") during surgery to remove the cancer. The dose of IORT, which is given with an electron beam in a specially equipped operating room, is between 25 and 40 Gray. There are facilities in the U.S.A. to give this treatment, at some large University Hospitals like Harvard and the Mayo Clinic. The Japanese and Chinese have shown a 20 - 30% improvement in survival when IORT was given, compared to none. In Japan, for stage III disease 62% of patients survived for 5 years after surgery with IORT, compared to just 37% for surgery alone. In China for stage III disease survival was 65% if IORTIORT, but could not prove improved survival-- but this trial was flawed since no patient got surgery alone. Again, more American Institutions are gettingIORT surgery suites; it should definitely be considered for the patient who wishes to be aggressive.

There is a Radiation Therapy Oncology Group ("RTOG") pilot study to see the results of maximizing available therapies for stomach cancer. Patients get 2 "cycles" of FAM neoadjuvant chemotherapy, maximal surgery to remove cancer, IORT, and then External Beam radiation with simultaneous 5-FU chemotherapy . It will be interesting to see if this drastic therapy significantly improves survival in stomach cancer. If so, it may become standard in those who can tolerate it.

What About Advanced Stomach Cancer?

When stomach 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". 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

As mentioned, radiation treatment can be very helpful for metastatic stomach cancer. A relatively new method of radiation for spread to the brain 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 stomach has had maximal radiation, and is still obstructed, a "stent" tube may be put in to bypass the tumor and still allow for mouth feedings, or a feeding tube may be placed directly into the intestine. Placement of a permanent feeding tube for unreliable obstruction is a choice to be made by the patient, family, and clergy.

The patient with newly diagnosed stomach 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.