OVERVIEW
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.
RISK FACTORS
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
DIFFERENT TYPES OF STOMACH CANCER
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.
SCREENING AND EARLY DETECTION
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.
DIAGNOSIS
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.
CHOOSING A TREATMENT FACILITY
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
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.
TREATMENT
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.
CHEMOTHERAPY
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
