The Causes And Mechanism Of Gastric Cancer

Published Date: 02 Nov 2017

Stomach cancer, or gastric cancer, is the uncontrolled growth arising from any part of the stomach. Gastric cancer is a cause of substantial morbidity and mortality. According to global database, gastric cancer is the fourth most common cancer, with an incidence that varies greatly across different geographic locations. Gastric cancer is the most common gastrointestinal tumor after pancreatic and colorectal cancer. Incidence of stomach cancer is decreasing worldwide, but still stomach cancer causes 3% to 10% of all cancer-related deaths.

The stomach is an expanded part of the digestive tube that lies beneath the ribs. It receives the softened food from the esophagus. Mixing and partial digestion of the food is carried out in the stomach with the help of its gastric secretions and food is converted into a pulpy fluid which then passes into the small intestine for further digestion and absorption. Stomach consists of 5 layers; mucosa, submucosa, muscularis mucosae, muscular layer and serosa. Lining cells and glands secrete enzymes, muscular layer helps in food digestion and outermost layer gives protection.

Causes and Risk factors

Causes and mechanism of gastric cancer

Chronic gastritis associated with H. pylori infection is the major cause of stomach cancer. Gastritis is generally accompanied by loss of gastric cells and structure. The mechanisms of malignant transformation are not entirely clear. Chronic inflammation induced by H. pylori may release toxic substances, which eventually cause DNA damage.

Whatever the cause is the basic mechanism of cancerous growth is the same. Cancer is an uncontrolled growth and it starts with an error in the DNA. This error is called mutation. DNA is the genetic material of cell. When mutation occurs it causes cell to grow and divide at a very rapid rate that is uncontrolled. Rapidly growing cancer cells compromise the blood supply of normal cells, as a result normal cells die. These cancer cells accumulate to form a lump and can penetrate the surrounding tissues. The cancer cells can move through blood and other medium and spread throughout the body.

Among the cancers that occur in the stomach, adenocarcinoma is tremendously the most important and the most common (90% to 95%). Next in order of frequency are lymphomas (4%), carcinoids (3%), and stromal tumors (2%).

Types of gastric cancer

Stomach cancer is of following types;

Gastric adenocarcinoma

Gastric adenocarcinoma is of two types, called intestinal and diffuse. The intestinal type is characterized by expansile or ulcerative growth and arises from gastric mucous cells. Intestinal type of adenocarcinoma is associated with chronic gastritis caused by H. pylori infection. This pattern of cancer tends to have good prognosis. In contrast, the diffuse type exhibits inward and diffuse growth pattern and it has poor prognosis. The cause of diffuse type carcinoma is unknown. Whereas the intestinal-type carcinoma occurs primarily after age 50 years with a 2 : 1 male predominance, the diffuse carcinoma occurs at an earlier age with female predominance.

Carcinoid tumors

These tumors arises from hormone producing cells of stomach.The peak incidence of these neoplasms is in the sixth decade, but they may appear at any age.

Gastric MALT lymphomas

These tumors arise from immune cells, as a result of Helicobacter-associated chronic gastritis. Lymphomas arising from stomach generally have a better prognosis. This type of gastrointestinal lymphoma usually affects adults, lacks a sex predilection.

GISTs

GIST occurs most commonly in the stomach. GIST occurs uniformly across all geographic and ethnic groups, and affects men and women equally. It is predominantly seen in patients >40 years old and is only rarely reported in children.

Risk factors

Several major variables are thought to affect the growth of this form of cancer. Few risk factors of stomach cancer are as follow;

Chronic gastritis

Helicobacter pylori infection

Nitrites are derived from nitrates which are found in food and drinking water, and used as preservatives in prepared meats.

Diets containing smoked foods, pickled vegetables and excessive salt intake.

Partial gastrectomy

Pernicious anemia

Gastric polyps are small elevations from stomach inner lining.

Decreased intake of fresh vegetables and fruits

Smoking

Food contaminated with aflatoxin fungus

Family history of stomach cancer

Being older or male

Eating foods that have not been stored appropriately

Complications

The complications that can be experienced by patients of stomach cancer may include;

Malabsorption

When tumor mass blocks the food passage it results in decrease absorption of food.

Malnutrition

Malabsorption leads to loss of essential nutrients

Bowel obstruction

Extensive tumors can obstruct stomach and gastrointestinal tract. Food cannot pass through intestine which results in vomiting.

Gastrointestinal bleeding

This comprises of vomiting blood or passing blood through stool.

Weight loss

Gastric perforation

Stomach may rupture due to infiltration of cancer

Difficulty in swallowing

Swelling of lower abdomen

Abdominal bloating after eating

Metastasis

Stomach can spread throughout the body and this process is called metastasis. Cancer may spread to the liver and causes complications like jaundice (yellow discoloration of body) and ascites (fluid accumulation in the abdominal cavity)

Death

Advanced stomach cancer will severely affect digestion and nutrition and may spread to other parts of the body, finally causing death.

Pharmaceutical therapies

The treatment therapy for stomach cancer depends on the stage of the cancer and health of the patient.

Surgery

Surgery to remove the stomach which is called gastrectomy is the only treatment that can treat the condition. When the cancer is at stage 1 the doctors most likely use surgery to treat the cancer. Surgical options include;

Laparoscopy: A small incision to push a tube with camera inside your stomach to understand the location of the cancer is and to decide for the subsequent surgery.

Partial Gastrectomy: Remove a part of the stomach

Total Gastrectomy: Remove all of the stomach. This may even include surrounding area such as oesophagus, intestine or the spleen depending upon the spread of tumour.

Lymph node dissection: Remove some or all of the lymph nodes

Create a bypass from the esophagus straight to the intestine

Endoscopic Laser surgery

Gastrectomy is major surgery. For a certain period of time after the surgery, the patient's activities are restricted to allow healing to take place. After surgery patient is fed intravenously (through a vein) and after few days, patients are ready for liquids and then solid foods. Patients who have had their complete stomach resected cannot absorb vitamin B12 that is essential for healthy blood and nerves, so they get regular injections of vitamin B12. Patients may also need to change their diet. The doctor or a nutrition specialist will describe any required dietary changes.

After surgery many patients experience cramps, dizziness nausea and diarrhea shortly after eating because liquid and food directly enter the small intestine. These symptoms can be treated by altering the patient's diet. Patient is advised to eat small meals at several times throughout the day and to avoid foods that contain sugar. The symptoms typically disappear in 3 to 12 months, but in few cases they may be lasting.

For those patients who cannot have surgery, chemotherapy or radiotherapy can improve the symptoms and may extend survival, but will not cure the cancer. For some patients, a surgical bypass procedure may be helpful to relieve symptoms.

Radiotherapy

Radiotherapy is rarely used in the cure of stomach cancer because it damages the surrounding organs like the liver. The main purpose of its use is to stop bleeding, reduce the pain or to shrink the size of the tumor when it is blocking the stomach passage.

For some people, radiation therapy causes minimal no side effects. For others, the side effects can very severe. The side effects of radiation therapy differ according to type and location of cancer, treatment plan, and the patient's general health. Side effects to radiotherapy include infections, nausea, vomiting or diarrhea. The doctor may prescribe medicine or recommend dietary changes to relieve these symptoms. The skin, where radiotherapy was given, may become red, dry, painful to touch, and itchy. Patients should not wear those clothes that can rub; loose cotton clothes are generally best.

Chemotherapy

Chemotherapy is used only when the stomach cancer is difficult to operate; or when the cancer is in advance stage and has started to spread throughout the body. It can be used prior to surgery to reduce the size of the tumor, or after surgery to decrease the risk of recurrent cancer after surgery. It can also be used to slow down the spread of cancer and to improve the quality of life, if an operation to remove the cancer isn’t recommended.

Chemotherapy can be taken in forms of tablets, or can be given into a vein by means of intravenous injections or drips (infusions).The most common drugs used are Taxol, Cisplatin, Epirubicin, Lomustine, Fluorouracil, Methotrexate and Mitomycin. Capecitabine and oxaliplatin are the new drugs using now-a-days.

Chemotherapy can cause many side effects, but these can generally be controlled with medicines. The major side effects are lowered resistance to infections, feeling sick, diarrhea, nausea, vomiting, sore mouth, sore hands and feet, anemia, bruising, bleeding, hair loss, tiredness, numbness in hands and feet etc. These effects usually go away slowly after the stomach cancer treatments stop or during the recovery period between treatments.

Biological Immune Therapies

This is a new range of therapy. In this monoclonal antibodies or vaccines, which are prepared from the cancer cells, are injected in patient’s body to increase immune response to fight against cancer.

Treatment plan according to stage of stomach cancer

Stage 0

Cure of stage 0 is usually surgery that is total or subtotal gastrectomy

Stage I

Treatment of stage I gastric cancer includes:

Total or subtotal gastrectomy

Total or subtotal gastrectomy with subsequent chemotherapy and radiationtherapy.

A clinical trial of chemotherapy and radiationtherapy is also given before surgery.

Stage II

Treatment of stage II gastric cancer includes:

Total or subtotal gastrectomy

Total or subtotal gastrectomy with subsequent chemotherapy and radiation therapy or just chemotherapy

Chemotherapy should be given before and after surgery.

Stage III

Treatment of stage III gastric cancer includes the following:

Total gastrectomy

Surgery followed by chemotherapy and radiotherapy or just chemotherapy.

Chemotherapy should be given before and after surgery

Stage IV and Recurrent stomach Cancer

Treatment of stage IV or recurrent stomach cancer includes the following:

Chemotherapy to relieve symptoms and to improve the quality of life

Therapy with a monoclonal antibody combined with chemotherapy.

Laser therapy to reduce the size of tumor

Stent placement to relieve an obstruction in the stomach

Radiation therapy to stop bleeding, to relieve pain, or to shrink a tumor that is blocking the stomach

Surgery to stop bleeding or shrink the size of tumor that is blocking the stomach

Lifestyle factors, Support and Prevention

We are not sure about what is the cause of stomach cancer, therefore there's no approach to prevent it. But you can take few steps to decrease your risk of stomach cancer by creating minor changes to your everyday life. The following suggestions may help reduce your risk of gastric cancer and improve lifestyle:

Don't smoke

Eat a healthy and balanced diet that is rich in fruits and vegetables

Don’t take salty and smoked foods.

Take herbs and other foods that don't add sodium.

Take a medication to treat stomach disease

Eradication of H. pylori infection at early stage

Mass screening programs have been effective at identifying disease in the early stages. Consider regular endoscopy to look for stomach cancer

The Cabbage Diet alkalizes the body and maintains a normal pH in stomach. The cabbage is also anti-inflammatory and it helps in digestion. Cabbage can destroy the foreign and causal bacteria of stomach.

Support

After being diagnosed with stomach, try to learn about stomach cancer. Ask your doctor about the details of your cancer including its type, stage and treatment options. Converse your preferences and concerns about treatments with your doctor.

You can comfort the trauma of illness by joining any support group with supporters who share common problems and experiences.

Eating healthy and getting enough rest can help fight against the stress and fatigue of cancer. Stay active. If you are diagnosed with cancer it doesn't mean you have to end doing the things you enjoy or usually do.

Natural treatment

Aloe vera

Aloe vera is a medicinal plan. Aloe vera seems to prove beneficial in the treatment of stomach cancer. It kills H. pylori bacteria. Approximately 90% of patients with gastric cancer have H. pylori bacteria in their stomach. It also inhibits acid secretion from the stomach. Excess acid production causes gastritis. H. Pylori bacterias enhance inflammation in the stomach. Aloe vera prevents inflammation in many different means. Some of the ingredients that are found in aloe vera may have helpful effects on the body’s immune system and can shrink the size of cancers. Studies show that patients taking the aloe vera with chemotherapy had an improved quality of life and they had less chemotherapy side effects for example fatigue and numb fingers. There are no ill effects from the aloe vera. Patients who take the aloe vera have 3 years survival rate than patients who just have chemotherapy.

Black cumin

Black cumin seeds have been used for centuries to treat a variety of diseases. Its scientific name is "Nigella sativa," The crude oil and thymoquinone (TQ) obtained from its seeds are effective against several diseases like cancer, diabetes mellitus, cardiovascular complications, kidney disease, asthma etc. Research suggests that the black seed is an effective anti-tumor treatment for stomach cancer. Black cumin, have been experimented in the lab and found to have potent anti-cancer and antioxidant effects. Antioxidants are chemicals that cleared the body of free radicals that cause cell damage and stimulate disease. The oil, extract or TQ component can kill cancer cells and protect healthy tissues during treatment.

Curcumin

Curcumin is a polyphenol obtained from the plant Curcuma longa, generally called turmeric. It is also called diferuloylmethane. Extensive research of the last 50 years has showed that this polyphenol can both treat and prevent cancer. Several studies recommend that curcumin has massive potential in the prevention and therapy of stomach cancer. It inhibits growth and production of human gastric cancer and is mainly effective in preventing cancers that have developed resistance to chemotherapy. Infection with the Helicobacter pylori (H. pylori) bacterium is a well-known cause gastric cancer. Curcumin limits growth of H. pylori and diminishes the rate at which stomach cells react to infection by turning into cancer cells. Curcumin is found to be safe and has no side effects.

EGCG

Epigallocatechin gallate, or EGCG, is an antioxidant present in tea. Tea is one of the most widely consumed beverages, second only to water. The cancer-defending effects of green tea have been stated in several studies. Cancer rates are low in countries for example, Japan where green tea is consumed on a regular basis. Several animal and clinical studies propose that EGCG play a significant role in the prevention of stomach cancer. It has been recommended that EGCG and other tea constituents such as catechins suppress tumor progression by inhibiting the release of tumor factors. The exposure of human stomach cells to EGCG results in both growth inhibition and the stimulation of programmed cell death (apoptosis). EGCG have been shown to prevent DNA damage caused by free radicals. DNA damage can cause cells to malfunction and lead to a number of health issues including cancer. Studies involving large populations of people suggest that drinking green tea may be associated with a lower risk of some cancer types.

Quercetin

Quercetin is a plant-based chemical and also known as a flavonoid. Quercetin is a dietary antioxidant and found in many plants and foods. It is an important component of berries, red wine, onions, buckwheat, tea green tea and apples. Quercetin is used as a medicine and it also has anti-proliferative activities against gastric cancer. Quercetin is a cancer chemopreventive agent that prevents tumor promotion by causing cell cycle stop and promoting cell death. Quercetin appears to have with little toxicity when administered orally or intravenously.

Resveratrol

Resveratrol is a naturally occurring polyphenol with potent anticancer activity. It has since been found in many plants, including berries, grapes and peanuts. Studies suggested that resveratrol induces tumor cell death via reactive oxygen species. Resveratrol inhibit proliferation of a number of cell lines and exhibits anticancer properties, by its capability to decrease proliferation of different types of tumor cells, comprising lymphoma, melanoma, multiple myeloma, squamous cell carcinoma, cancers of the prostate, breast, stomach, ovary, cervix, colon, pancreas, and thyroid. Resveratrol might produce anticancer effects by its antioxidant action. It stimulates NOS to produce low levels of NO, which, in turn, exert antioxidant action. Consumption of a resveratrol rich diet is advised because of its protective role against gastric cancer. According to research resveratrol is pharmacologically safe and have no side effects.

There are a number of vitamins and supplements that may help in stomach cancer and enhance the immune system. Research suggested that vitamin D, fish oils and natural vitamins like vitamin E has anticancer effect in Gastro-intestinal cancers.