About Stomach Cancer

Gastric cancers - those that begin in the stomach, esophagus or the junctions of those two organs - account for 37,600 new cancer cases in the United States each year and 25,150 deaths.  Of these, 21,000 are stomach cancers resulting in 10,600 deaths each year.  While the incidence of stomach cancer has been dropping steadily in this country since World War II, it remains a major global health problem and is estimated to be the fourth most common cancer worldwide and the second leading cause of death.  Japan, China, Korea, Taiwan, Costa Rica, Peru, Brazil, Chile, and the former Soviet Union all have a very high incidence of gastric cancer.  This high incidence is believed to be related to eating a diet consisting of heavily smoked, salted, and pickled foods. 

The primary risk factors for stomach cancer are:
-       Infection with a bacteria known as Helicobacter pylori (H pylori) which is associated with gastric ulcers and a condition known as chronic atrophic gastritis.  The exact role of H pylori remains unclear, but it is thought that it causes an inflammation of the stomach which can lead to the loss of secretory cells which eventually results in cancer.
-       Pernicious anemia is an autoimmune disease in which the stomach does not produce stomach acid.  This condition has also been linked to stomach cancer.
-       Genetic factors including hereditary nonpolyposis colorectal cancer, familial adenomatous polyposis, and Peutz Jeghers syndrome all predispose people to stomach cancer.  It also appears that people with type A blood are at increased risk.
-       Being of Asian descent although the incidence of stomach cancer declines sharply in second and third generation Japanese and Chinese immigrants to the United States.
-       Diets heavy in salt and smoked foods, smoking and tobacco use

Virtually all stomach cancers are adenocarcinomas, meaning that the cancer begins in the glandular tissue that lines the inside of the stomach.  Adenocarcinomas are further classified as either intestinal or diffuse.  This is important because the classification influences the treatment and outcome of the disease.
-       Intestinal gastric cancer (also known as non-cardia gastric cancer) is thought to result from chronic inflammation, such as that caused by infection with H pylori bacteria, and to follow a step-by-step progression from chronic gastritis to malignancy.  Environmental factors such as smoking, high salt intake, and alcohol consumption are all risk factors for this type of stomach cancer.
-       Diffuse gastric cancer does not begin with a pre-malignant condition and does not appear to be related to environmental factors such as diet or smoking, although infection with Helicobacter pylori raises the risk of this disease as well.  The most important factor in diffuse gastric cancer is a genetic mutation that silences a gene called E-cadherin.  Approximately 50% of patients with this type of stomach cancer have this gene mutation.  There is also a hereditary form of diffuse gastric cancer (HDGC) which is caused by the loss of function in the CDH1 gene.  People with this syndrome have a very high risk of stomach cancer.

In parts of Asia where stomach cancer is highly prevalent, aggressive screening programs have had some success in detecting early cancers and improving the outcomes, but in the United States there are no effective screening methods and no established programs for primary prevention or early detection.  In addition, the symptoms of stomach cancer are not specific and are common to many gastric problems such as ulcers and gastritis.  They include abdominal discomfort, indigestion, loss of appetite, occasional vomiting, and a feeling of fullness after eating small amounts of food. Up to 25% of patients will have a history of gastric ulcers. 
Up to now screening programs have relied on tests known as "upper GIs" or barium swallows and upper endoscopies.  These procedures are somewhat analogous to the use of colonoscopy to detect pre-cancerous and early cancerous colon and rectal lesions.  Because of the low incidence of stomach cancer in this country combined with the high cost of these tests, most experts believe that wide-scale screening for stomach cancer would cause more problems than it would solve.  More recent studies have investigated the use of a blood marker called the serum pepsinogen I/II ratio to detect atrophic gastritis and gastric cancer, but this approach is still in the very early stages of investigation.

The most common procedure used to diagnose gastric cancer is upper endoscopy.  Using this method, a doctor can visualize the gastrointestinal tract, obtain a biopsy of the tumor, and diagnose up to 95% of gastric cancer cases.  This is often combined with ultrasound to identify how deeply the cancer has penetrated the wall of the stomach and whether the tumor has spread to adjoining lymph nodes, both very important factors in determining the stage of the disease and deciding on appropriate treatment.  Other tests used to establish the stage of the disease are CAT scans of the abdomen and chest, PET scans, MRIs, and laparoscopy, which is a surgical procedure that uses a fiber optic camera to view the organs and tissues directly.

Stomach cancer is a very serious disease.  Its diagnosis, staging, and treatment are all complex and require an experienced, skilled team of medical professionals working together.  This team includes surgeons, pathologists, radiologists, oncologists, radiation therapists, gastroenterologists, and support personnel to deal with the many physical and psychosocial challenges posed by gastric cancer.  For this reason, it is very important for patients to have at least the initial phases of their staging and treatment at a cancer center or academic medical center which treats a large number of gastric cancers and can offer this multidisciplinary approach.  Once the initial treatment is complete, it may be possible for many patients to return to their community hospitals to receive their follow-up care in that setting.

Staging is the process by which doctors determine the extent to which a cancer has spread. This is critical in deciding on the appropriate course of treatment.  Staging is generally done by classifying the cancer in three ways: the nature and extent of the tumor, the T in staging; its spread to lymph nodes, the N in staging; and its spread to other parts or organs in the body, the M in staging.  Staging for gastric cancers is complex and includes many factors, but overall, cancers are described on scale of I-IV based on the combination of the T N and M, with I being the earliest or most limited form of the disease and IV the most advanced. 
-       Stage IA: The cancer is confined to the stomach and may have invaded the inner layer of the stomach wall but has not spread to any lymph nodes or other organs.
-       Stage IB: The cancer has grown into the inner layers of the stomach wall and has spread to one or two lymph nodes but not anywhere else, or the cancer has grown into the outer muscular layers of the stomach but has not spread to the lymph nodes or other organs. (T2, N0, M0)
-       Stage IIA: The cancer has invaded the inner layer of the stomach and has spread to three to six lymph nodes; or the cancer has invaded the outer layers of the wall and has spread to one to two lymph nodes; or the cancer has grown through all the layers of muscle into the connective tissue outside the stomach but has not penetrated the peritoneal lining or spread to any lymph nodes or to surrounding organs.
-       Stage IIB: The cancer has invaded the inner layers of the wall of the stomach and spread to six or seven lymph nodes; or has invaded the outer layers and spread to three to six lymph nodes; or has spread to the connective tissue outside the stomach but not penetrated the peritoneum and has spread to one or two lymph nodes; or has penetrated the peritoneum but not spread to any lymph nodes.
-       Stage IIIA: The cancer has invaded the outer muscular layers of the stomach and has spread to six or more lymph nodes; or has grown through all the muscular layers of the stomach, has not penetrated the peritoneum, but has spread to three to six lymph nodes; or the cancer has penetrated the peritoneum and has spread to one to two lymph nodes but not other organs.
-       Stage IIIB: The cancer has grown through all the layers of the muscle into the connective tissue outside the stomach, has not penetrated the peritoneal lining, but has spread to seven or more lymph nodes; or the cancer has grown through all the layers of muscle, has penetrated the peritoneal lining and has spread to three to six lymph nodes; or the cancer has grown through all the layers of muscle into the connective tissue outside the stomach, has invaded nearby organs or structures and may or may not have spread to one to two lymph nodes.
-       Stage IV: The cancer has spread to distant parts of the body besides the area around the stomach.
When a cancer returns or recurs after initial treatment, the staging usually changes to reflect the extent of the disease.  Recurrences can be local, meaning that they occur at or near the site of the original tumor, or may be a distant metastasis, meaning that the cancer appears in another part of the body.

The treatment for stomach cancer depends on its stage--the size and location of the tumor, whether the cancer has spread, and the patient's overall health.  Surgery is the essential component to all curative treatments for gastric cancer.  The goal of surgery for potentially curable stomach cancer is to remove all of the cancer while preserving as much of the patient's normal function as possible.  All stomach cancer surgery is complex and should be performed by an experienced surgical oncologist.
When the cancer is confined to the stomach, the surgery usually consists of removing the affected portion of the stomach and the nearby lymph nodes, a procedure known as gastrectomy.  Gastrectomy can be either partial or total removal of the entire stomach.  The surgical decision is based on the location of the tumor and the type of stomach cancer involved.
Although surgery is an essential part of any curative approach to stomach cancer, surgery alone is often not enough.  Most patients with potentially curable gastric cancer, Stages IB and II, will require additional therapy to prevent the cancer from recurring or coming back.  These patients receive radiation or chemotherapy to kill any cancer cells that might remain after surgery.  These additional, or adjuvant, treatments are sometimes used prior to surgery to shrink the tumor.  According to current guidelines, the standard of care for stomach cancer patients with potentially curable disease who are stage IB or higher is surgery to remove all of the cancer and the adjacent lymph nodes; radiation therapy beginning 4-6 weeks after surgery; and chemotherapy given during and after the radiation or sometimes before beginning radiation.  This approach has been shown to significantly reduce the recurrence rate in stomach cancer patients.
For more advanced disease, Stages III and IV, the basic approach to initial treatment is the same: surgery to reduce the amount of tumor, radiation, and chemotherapy.  These cancers, however, will not be cured by surgery.  The goal of treatment in these cases is to control the growth of the cancer for as long as possible and to reduce or relieve any symptoms that result from the cancer.  The amount and type of treatment depend on the extent of the cancer and the overall health of the patient.

Patients with advanced or metastatic gastric cancer can benefit from chemotherapy in managing both their disease and its symptoms.  A number of studies have shown that patients undergoing chemotherapy had a higher quality of life than those receiving best supportive care. There are currently a number of drugs, combinations of drugs, and targeted therapies that have been shown to be effective in extending the lives of patients with advanced gastric cancer.  There are also multiple clinical trials underway designed to test new agents and improve the uses of established ones.  Choosing the right chemotherapy regimen depends on a number of factors including the location and extent of the disease, its molecular profile, previous treatment, potential side effects or toxicity, and the overall health of the patient.  Many patients with advanced gastric cancer suffer from significant physical symptoms related to their cancer and may not be candidates for some types of chemotherapy.
One of the major limiting factors in cancer treatment is a phenomenon known as drug resistance.  This occurs when a drug or drugs that have been effective in controlling a cancer stop working. The reasons for this are very complex and are being studied by researchers around the world.  For gastric cancer, there are second and third line chemotherapy regimens that can be used once the first line therapy fails. 
Patients should be seen in cancer centers that can provide multidisciplinary approaches, see a high volume of gastric cancer patients and have the ability to address the multiple symptoms and side effects that are consequences of both the cancer and its treatment.  Patients should also be aware of the possibility of enrolling in clinical trials and discuss these options with their treatment team.  As with all treatment options for gastric cancer, especially in its advanced stages, the decisions regarding appropriate therapy are complicated.

Sources for this information:
-       cantstomachcancer.org
-    cancer.net
-       oncolink.org
-       mayoclinic.org
-       NCCN Clinical Practice Guidelines for Gastric Cancer
-       Gastric Cancer: A Primer on the Epidemiology and Biology of the Disease and an Overview of the Medical Management of Advanced Disease, Manish A. Shah and David P. Kelsen, JNCCN, Vol.8, Number 4, April 2010
-       Multimodality Approaches to Localized Gastric Cancer, Prajnan Da, Yixing Jiang, Jeffrey H. Lee, S. Bhutai, William A. Ross, Paul F. Mansfield, Jaffer A. Ajani, JNCCN, Vol. 8, Number 4, April, 2010
-       Update on Gastric Cancer: Molecular Pthology and Targeted Therapies; Antonia R. Sepulveda, PhD.; USGIPS.com/documents