| Gastric cancer | |
|---|---|
| Classification and external resources | |
A suspicious stomach ulcer that was diagnosed as cancer on biopsy and resected. Surgical specimen. |
|
| ICD-10 | C16 |
| ICD-9 | 151.9 |
| OMIM | 137215 |
| DiseasesDB | 12445 |
| eMedicine | med/845 |
| MeSH | D013274 |
Stomach cancer, or gastric cancer, refers to cancer arising from any part of the stomach. Stomach cancer causes about 800,000 deaths worldwide per year.[1]
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Stomach cancer is often asymptomatic or causes only nonspecific symptoms in its early stages. By the time symptoms occur, the cancer has often reached an advanced stage (see below), one of the main reasons for its poor prognosis. Stomach cancer can cause the following signs and symptoms:
Stage 1 (Early)
Stage 2 (Middle)
Stage 3 (Late)
Note that these can be symptoms of other problems such as a stomach virus, gastric ulcer or tropical sprue.
Infection by Helicobacter pylori is believed to be the cause of most stomach cancer while autoimmune atrophic gastritis, intestinal metaplasia and various genetic factors are associated with increased risk levels. The Merck Manual states that diet plays no role in the genesis of stomach cancer.[2] However, the American Cancer Society lists the following dietary risks, and protective factors, for stomach cancer: "smoked foods, salted fish and meat, and pickled vegetables (appear to increase the risk of stomach cancer.) Nitrates and nitrites are substances commonly found in cured meats. They can be converted by certain bacteria, such as H. pylori, into compounds that have been found to cause stomach cancer in animals. On the other hand, eating fresh fruits and vegetables that contain antioxidant vitamins (such as A and C) appears to lower the risk of stomach cancer."[3] A December 2009 article in American Journal of Clinical Nutrition found a statistically significant inverse correlation between higher adherence to a Mediterranean Dietary Pattern and stomach cancer.[4]
In more detail, H. pylori is the main risk factor in 65–80% of gastric cancers, but in only 2% of such infections.[5] Approximately ten percent of cases show a genetic component.[6] Some studies indicate that bracken consumption and spores are correlated with incidence of stomach cancer, though causality has yet to be established.[7]
A very important but preventable cause of gastric cancer is tobacco smoking. Smoking increases the risk of developing gastric cancer considerably; from 40% increased risk for current smokers to 82% increase for heavy smokers which is nearly twice the risk for non-smoking population. Gastric cancers due to smoking mostly occur in upper part of stomach near esophagus[8][3][9] Another lifestyle cause of gastric cancer besides smoking is consumption of alcohol.[10][11][12] Alcohol as cause of cancer along with tobacco smoking as cause of cancer increase the risk of developing other cancers as well.
Gastric cancer shows a male predominance in its incidence as up to three males are affected for every female. Estrogen may protect women against the development of this cancer form.[13] A very small percentage of diffuse-type gastric cancers (see Histopathology below) are thought to be genetic. Hereditary Diffuse Gastric Cancer (HDGC) has recently been identified and research is ongoing. However, genetic testing and treatment options are already available for families at risk.[14]
Some researchers[15][16][17][18][19][20] showed a correlation between Iodine deficiency or excess, iodine-deficient goitre and gastric cancer; a decrease of the incidence of death rate from stomach cancer after implementation of the effective I-prophylaxis was reported too.[21] The proposed mechanism of action is that iodide ion can function in gastric mucosa as an antioxidant reducing species that can detoxify poisonous reactive oxygen species, such as hydrogen peroxide.
The International Cancer Genome Consortium is leading efforts to map stomach cancer's complete genome.
To find the cause of symptoms, the doctor asks about the patient's medical history, does a physical exam, and may order laboratory studies. The patient may also have one or all of the following exams:
Abnormal tissue seen in a gastroscope examination will be biopsied by the surgeon or gastroenterologist. This tissue is then sent to a pathologist for histological examination under a microscope to check for the presence of cancerous cells. A biopsy, with subsequent histological analysis, is the only sure way to confirm the presence of cancer cells.
Various gastroscopic modalities have been developed to increased yield of detect mucosa with a dye that accentuates the cell structure and can identify areas of dysplasia. Endocytoscopy involves ultra-high magnification to visualize cellular structure to better determine areas of dysplasia. Other gastroscopic modalities such as optical coherence tomography are also being tested investigationally for similar applications.[22]
A number of cutaneous conditions are associated with gastric cancer. A condition of darkened hyperplasia of the skin, frequently of the axilla and groin, known as acanthosis nigricans, is associated with intra-abdominal cancers such as gastric cancer. Other cutaneous manifestations of gastric cancer include tripe palms (a similar darkening hyperplasia of the skin of the palms) and the sign of Leser-Trelat, which is the rapid development of skin lesions known as seborrheic keratoses.[23]
Various blood tests may be done; including: Complete Blood Count (CBC) to check for anemia. Also, a stool test may be performed to check for blood in the stool.
If cancer cells are found in the tissue sample, the next step is to stage, or find out the extent of the disease. Various tests determine whether the cancer has spread and, if so, what parts of the body are affected. Because stomach cancer can spread to the liver, the pancreas, and other organs near the stomach as well as to the lungs, the doctor may order a CT scan, a PET scan, an endoscopic ultrasound exam, or other tests to check these areas. Blood tests for tumor markers, such as carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) may be ordered, as their levels correlate to extent of metastasis, especially to the liver, and the cure rate.
Staging may not be complete until after surgery. The surgeon removes nearby lymph nodes and possibly samples of tissue from other areas in the abdomen for examination by a pathologist.
The clinical stages of stomach cancer are:[26][27]
The TNM staging system is also used.[28]
In a study of open-access endoscopy in Scotland, patients were diagnosed 7% in Stage I 17% in Stage II, and 28% in Stage III.[29] A Minnesota population was diagnosed 10% in Stage I, 13% in Stage II, and 18% in Stage III.[30] However in a high-risk population in the Valdivia Province of southern Chile, only 5% of patients were diagnosed in the first two stages and 10% in stage III.[31]
As with any cancer, treatment is adapted to fit each person's individual needs and depends on the size, location, and extent of the tumor, the stage of the disease, and general health. Cancer of the stomach is difficult to cure unless it is found in an early stage (before it has begun to spread). Unfortunately, because early stomach cancer causes few symptoms, the disease is usually advanced when the diagnosis is made. Treatment for stomach cancer may include surgery, chemotherapy, and/or radiation therapy. New treatment approaches such as biological therapy and improved ways of using current methods are being studied in clinical trials. An antibody-drug conjugate IMGN242 is in phase II clinical trials.[32][33] There is a well known remedy that eating jalapeño peppers daily can help reduce the pain of stomach cancer. Some think this is because it reduces the gastric acid in your stomach and helps numb the stomach walls.
Surgery is the most common treatment. The surgeon removes part or all of the stomach, as well as the surrounding lymph nodes, with the basic goal of removing all cancer and a margin of normal tissue. Depending on the extent of invasion and the location of the tumor, surgery may also include removal of part of the intestine or pancreas. Tumors in the lower part of the stomach may call for a Billroth I or Billroth II procedure.
Endoscopic mucosal resection (EMR)[34] is a treatment for early gastric cancer (tumor only involves the mucosa) that has been pioneered in Japan, but is also available in the United States at some centers. In this procedure, the tumor, together with the inner lining of stomach (mucosa), is removed from the wall of the stomach using an electrical wire loop through the endoscope. The advantage is that it is a much smaller operation than removing the stomach. Endoscopic submucosal dissection (ESD) is a similar technique pioneered in Japan, used to resect a large area of mucosa in one piece. If the pathologic examination of the resected specimen shows incomplete resection or deep invasion by tumor, the patient would need a formal stomach resection.
Surgical interventions are currently curative in less than 40% of cases, and, in cases of metastasis, may only be palliative.
The use of chemotherapy to treat stomach cancer has no firmly established standard of care. Unfortunately, stomach cancer has not been particularly sensitive to these drugs, and chemotherapy, if used, has usually served to palliatively reduce the size of the tumor, relieve symptoms of the disease and increase survival time. Some drugs used in stomach cancer treatment have included: 5-FU (fluorouracil) or its analog capecitabine, BCNU (carmustine), methyl-CCNU (Semustine), and doxorubicin (Adriamycin), as well as Mitomycin C, and more recently cisplatin and taxotere, often using drugs in various combinations. The relative benefits of these different drugs, alone and in combination, are unclear.[35] Clinical researchers have explored the benefits of giving chemotherapy before surgery to shrink the tumor, or as adjuvant therapy after surgery to destroy remaining cancer cells. Combination treatment with chemotherapy and radiation therapy has some activity in selected post surgical settings. For patients who have HER2 overexpressing metastatic gastric or gastroesophageal (GE) junction adenocarcinoma, who have not received prior treatment for their metastatic disease, the US Food and Drug Administration granted approval (2010 October) for trastuzumab (Herceptin, Genentech, Inc.) in combination with cisplatin and a fluoropyrimidine (capecitabine or 5-fluorouracil). This was based on an improvement of the median overall survival (OS) of 2.5 months[36] with trastuzumab plus chemotherapy treatment compared to chemotherapy alone (BO18255 ToGA trial). The combination of Herceptin with chemotherapy for treating metastatic gastric cancer was also sanctioned by the European regulatory authorities (2010 January). Doctors have also tested putting the anticancer drugs directly into the abdomen, often with warmed solutions of the medication (intraperitoneal hyperthermic chemoperfusion).[37]
Radiation therapy (also called radiotherapy) is the use of high-energy rays to damage cancer cells and stop them from growing. When used, it is generally in combination with surgery and chemotherapy, or used only with chemotherapy in cases where the individual is unable to undergo surgery. Radiation therapy may be used to relieve pain or blockage by shrinking the tumor for palliation of incurable disease.
While previous studies of multimodality therapy (combinations of surgery, chemotherapy and radiation therapy) gave mixed results, the Intergroup 0116 (SWOG 9008) study[38] showed a survival benefit to the combination of chemotherapy and radiation therapy in patients with nonmetastatic, completely resected gastric cancer. Patients were randomized after surgery to the standard group of observation alone, or the study arm of combination chemotherapy and radiation therapy. Those in the study arm receiving chemotherapy and radiation therapy survived on average 36 months; compared to 27 months with observation.
Stomach cancer is the fourth most common cancer worldwide with 930,000 cases diagnosed in 2002.[40] It is a disease with a high death rate (~800,000 per year) making it the second most common cause of cancer death worldwide after lung cancer.[1] It is more common in men and in developing countries.[40][41]
It represents roughly 2% (25,500 cases) of all new cancer cases yearly in the United States, but it is more common in other countries. It is the leading cancer type in Korea, with 20.8% of malignant neoplasms.
Metastasis occurs in 80-90% of individuals with stomach cancer, with a six month survival rate of 65% in those diagnosed in early stages and less than 15% of those diagnosed in late stages.
One in 50 patients of all ages who seek medical attention for burping and indigestion are diagnosed with stomach cancer.[42] Out of 10 million people in the Czech Republic, only 3 new cases of stomach cancer in people under 30 years of age in 1999 were diagnosed.[43] Other studies show that less than 5% of stomach cancers occur in people under 40 years of age with 81.1% of that 5% in the age-group of 30 to 39 and 18.9% in the age-group of 20 to 29.[44]
For Taiwan (statistic not shown on the above map), the mortality was 11.75 per 100,000 (1996).
The stomach is a muscular organ of the gastrointestinal tract that holds food and begins the digestive process by secreting gastric juice. The most common cancers of the stomach are adenocarcinomas but other histological types have been reported. Signs vary but may include vomiting (especially if blood is present), weight loss, anemia, and lack of appetite. Bowel movements may be dark and tarry in nature. In order to determine whether cancer is present in the stomach, special X-rays and/or abdominal ultrasound may be performed. Gastroscopy, a test using an instrument called endoscope to examine the stomach, is a useful diagnostic tool that can also take samples of the suspected mass for histopathological analysis to confirm or rule out cancer. The most definitive method of cancer diagnosis is through open surgical biopsy.[45] Most stomach tumors are malignant with evidence of spread to lymph nodes or liver, making treatment difficult. Except for lymphoma, surgery is the most frequent treatment option for stomach cancers but it is associated with significant risks.
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