Gastric Cancer

What is Gastric Cancer?

Gastric cancer, also referred to as stomach cancer, is a cancer that starts in any part of the stomach and may spread to other parts of the stomach or to other organs at later stages. Depending on the section of the stomach where the cancer starts, the patient can be affected by different symptoms, and the treatment options available to them may vary. Stomach cancers tend to develop slowly over many years. Several pre-cancerous changes have to occur in the lining of the stomach for gastric cancer to manifest, and since these early changes are asymptomatic, they often go undetected. Between 90% and 95% of gastric tumors are adenocarcinomas, meaning that they develop from the mucosa of the stomach (the innermost lining).

Gastric cancer is the fourth most common cancer and second leading cause of cancer-related deaths in the world. It has been estimated that more than 989,600 new cases of gastric cancer are diagnosed each year worldwide, and at least 738,000 patients succumb to the disease. Although gastric cancer rates have decreased substantially in most parts of the world, it is still responsible for 10% of all cancer-related deaths. The increased use of refrigeration, availability of fresh fruit and vegetables, decreased reliance on salted and preserved foods and decreasing number of smokers worldwide have been mentioned as the main factors driving the decrease in gastric cancer incidence.

What Causes Gastric Cancer?

There is a general agreement in the medical community that infection with the bacterium Helicobacter pylori is the effective cause of most gastric cancers. The infection is typically acquired during childhood and can persist in the gastric ecosystem throughout the life span of the individual if untreated. H. pylori specifically colonizes the gastric mucosa and causes chronic gastritis. This may potentially evolve into more severe diseases such as atrophic gastritis, peptic ulcer, lymphoma of the lymphoid tissue associated with the mucosa, or gastric adenocarcinoma. According to some epidemiological studies, the risk for gastric cancer conferred by H. pylori is close to 75%. It is thought that H. pylori influences the early stages in the development of the gastric tumor, since its eradication only improves the outcome in patients without premalignant lesions at the time of diagnosis.

In addition to H. pylori infection, genetic factors also play an important role in the development of gastric tumors, with genetic variations in the genes DNMT3A, PSCA, VEGF and XRCC1 reported to be associated with the risk of gastric cancer. Whether the diet or other environmental factors also play a role is more controversial, but salt and salted food intake has been linked to an increased risk while an antioxidant diet rich in fruits and vegetables has been shown to reduce the risk. Tobacco smoking increases the risk dramatically, with the prevalence of gastric cancer in smokers reported to be twice as high compared to non-smokers.

Finally, the risk of developing gastric cancer is twice as high in males compared to females, leading to the speculation that some internal factor of male physiology contributes to the development of stomach tumors.

Symptoms of Gastric Cancer

Signs and symptoms that may be indicative of gastric cancer include:

• Poor appetite
• Unexplained weight loss
• Abdominal pain
• Vague discomfort in the abdomen, usually above the navel
• A sense of fullness in the upper abdomen after eating a small meal
• Heartburn, indigestion or ulcer-type symptoms
• Nausea
• Vomiting, with or without blood
• Swelling or fluid build-up in the abdomen

Although most of these symptoms can be caused by other conditions and their presence does not necessarily mean that the patient suffers from gastric cancer, if they persist for an extended period of time a professional should be consulted to rule out this possibility.

Diagnosis of Gastric Cancer

Symptoms of stomach cancer do not tend to become evident until the disease is advanced. This makes it particularly hard to detect it at an early stage and contributes to its difficult prognosis. In countries such as Japan, the implementation of mass serological screening has dramatically increased the number of gastric cancers detected at an early stage, and this in turn has contributed to a lower mortality rate. A protein called pepsinogen is usually used as a serological marker in combination with antibodies against H. pylori.

In countries where serological screening is not the norm, diagnosis of gastric cancer depends on a physical examination and critical evaluation of the patient’s medical history. If the physician determines that there are reasons to suspect the presence of a gastric tumor, the diagnosis has to be confirmed by endoscopy (insertion of a fiber optic camera into the stomach to visualize the lesion). Radiography (also known as barium roentgenogram) can be used for the same purpose, although it is considered less sensitive. The detection of an ulcer or a flat, thickened area of mucosa known as linitis plastica can raise suspicion of gastric cancer. If abnormal areas of these kinds are noted, a tissue sample is obtained (biopsy) and submitted to the pathologist for histological analysis. This would eventually confirm if there is any presence of cancerous cells.

Treatment of Gastric Cancer

Management strategies for gastric cancers depend critically on the stage of the disease at the time of diagnosis. Other factors such as the location of the lesion, the age and general state of health of the patient also come into play. Surgical resection still offers the best hope for a cure. In the past radical gastrectomy was advocated for all lesions, but today there is an array of less invasive methods available for treatment. For instance, endoscopic mucosal resection (a minimally invasive technique developed in Japan and Korea) is considered an effective treatment option for gastric cancer at an early stage. A slightly more aggressive version (endoscopic submucosal dissection) that involves the use of an electrocautery knife has also been developed.

When the disease is locally advanced or has already reached the metastatic stage, the benefits of surgery are much lower, but palliative surgery can nevertheless be offered to these patients to prevent gastric obstruction or bleeding and thus improve their quality of life.

Gastric cancers are not particularly sensitive to chemotherapy, and therefore its use is usually restricted to relieve symptoms of the disease and increase survival time. A combined regimen with the drugs epirubicin, cisplatin and fluorouracil has demonstrated the best results. Chemotherapy is also administered either after surgery (adjuvant treatment) or before surgery (neoadjuvant treatment). This combined strategy has been shown to improve treatment outcomes.

Prognosis of Gastric Cancer

The prognosis in gastric cancer is generally poor, unless it is detected at an early stage. In this latter case, up to half of the patients may expect to be cured from their disease without tumor recurrence. Unfortunately, the majority of patients in the U.S. already present late-stage or a metastatic disease at diagnosis, which is associated with a much more negative prognosis. The five-year survival rate has been estimated to be between 10% and 16% in Western countries.

Preventing Gastric Cancer

Given that the presence of H. pylori in the human gut is considered a key factor in the risk of developing gastric cancer. Eradication of the bacteria is an obvious way to prevent the disease. It is believed that the earlier the eradication, the more significant the decrease in the risk is, suggesting that a prophylactic vaccine against H. pylori administered at an early age could be an ideal strategy to prevent gastric cancer. Unfortunately, no effective vaccine against H. pylori is commercially available at present time, leaving antibiotics as the only alternative. However, the eradication rates attained using antibiotic regiments have been decreasing due to resistance.

Another effective way of preventing gastric cancer is by modifying daily habits that have been linked to an increased risk, such as excessive consumption of smoked and pickled foods, salted meats and fish, and tobacco smoking. A diet rich in fresh fruits and vegetables is recommended instead, along with food items with high levels of antioxidants such as green tea.

Living with Gastric Cancer

Those patients whose gastric tumor is detected at an early stage, and have a reasonable chance of recovery after treatment, can expect to have a good quality of life regardless of their disease. If they have had to undergo surgery, their eating habits would have to change to some degree and they may no longer be able to ingest large amounts of food at the same time. If the surgery was extensive (subtotal or total gastrectomy), the patient will need to take vitamin supplements regularly, including injections of vitamin B₁₂. In addition, a careful physical examination and review of symptoms every 4 to 6 months is recommended during the first three years after surgery.

If surgery failed to achieve total remission of the disease, the patient will need to get regular treatments with chemotherapy, radiation therapy, or other therapies aimed at keeping the tumor in check and preventing metastases. These sort of therapies are normally associated with weight loss, chronic lack of appetite and eating disorders, physical fatigue and mental depression. The emotional stress can be very high under these circumstances, just as with any other terminal illness.

Current Research of Gastric Cancer

Several advances in surgical methods are likely to improve the chances of complete remission after surgical treatment for gastric cancer in the near future. Laparoscopic surgery, in which the procedure is carried on through several small holes in the abdomen, is mostly restricted to Asian countries,  but it is slowly spreading to the Western world. Even more advanced alternatives to laparoscopy, such as Natural Orifice Translumenal Endoscopic Surgery (NOTES) and robotic surgery are leaving the developmental stage and being adopted as part of the standard toolbox against gastric cancer.

Targeted therapies with drugs such as bevacizumab (Avastin®), which prevents the development of blood vessels that supply nutrients to the tumor, are being tested in combination with standard chemotherapeutic agents, with promising results. Other drugs currently undergoing clinical trials act by boosting the ability of the patient’s own immune system to fight the tumor.