OVERVIEW OF GASTRIC CANCER

Gastric (stomach) cancer is one of the most common cancers in the world. It remained the most popular cancer in terms of incidence and fatalities in the world until lung cancer emerged finally as the most common. It is known to be very common in Japan. It affects males more than females. Cancer of the stomach should not be misappropriated for other cancers that are found in the abdomen.

The stomach is an opened, hollow, and pouch-like structure of the digestive tract that holds and stores food for chemical digestion by enzymes. Anatomical the stomach is made up of; cardia(Immediate part of reception from the esophageal), fundus, body(the main part which stores ingested food or central the part of the organ), pyloric region(contains the pyloric antrum and the pyloric canal). Malignant changes of the stomach can occur at any part of the stomach. The layers of the stomach from outside to inside is; serous layers, subserous, muscular layer, submucous layer, mucous layer.

When gastric cancers grow deep from the mucous membrane into the submucosa or further, the prognosis progressively becomes worse and poor. The epithelial cells are the main origin of stomach cancers. Each clinical presentation differs with respect to the functional proliferating cell; peptic or zymogenic cells(also called chief cells), parietal cells(oxyntic cells), mucous Cells, and enteroendocrine cells. Statistics prove that most gastric cancers are Adenocarcinomas. Gastric cancer can easily be cured surgically provided it is detected early. The early detection of gastric cancer is difficult due to the location of the stomach hence, mostly diagnosed in its metastatic stage with a worse prognosis.

Most common causes of gastric cancer are; Genetic mutations, chronic Helicobacter pylori infection, and diets. Aside from surgery, there are other treatment modalities for gastric cancer. Example; Radiotherapy and Chemotherapy.

WHAT IS GASTRIC CANCER?

Gastric or stomach cancer refers to cancer that originates from the cells of the stomach. It is defined as the abnormal growth of the cells in the stomach and the ability of the abnormal cells to invade nearby tissues or spread to distant organs.

This abnormal malignancy normally forms in the glandular epithelial layer of the stomach. Gastric cancer mostly occurs in pyloric area (65%), the body (25%), and the fundus.

 TYPES OF GASTRIC CANCERS

 

1. CLASSIFICATION BASED ON HISTOLOGY

This is the histological classification of gastric cancer under a microscopic study.

A. Adenocarcinoma of the stomach:

This refers to the type of gastric cancers that develop from the glandular epithelial cells. This is the most common type of gastric cancer. It accounts for about 95% of all gastric cancers diagnosed in the world. This type of gastric cancer normally occurs in the inner layer of the stomach called the mucosa layer. There are several subtypes of gastric adenocarcinoma, some of these are;

i. Papillary Gastric Adenocarcinoma:

This is one of the most common adenocarcinoma subtypes. It mostly originates from the proximal parts of the stomach. Spread is usually to the liver and does not invade the serous membrane of the stomach. It is known by abnormal cells with round finger-like projections called papillae. These projections grow and point into the stomach cavity. Also, it mostly affects the old aged than the young.

ii. Tubular Gastric Adenocarcinoma:

This type of adenocarcinoma is known by abnormal gastric cells with tube-shaped branches called tubules. It is one of the most common types of adenocarcinomas which does not invade the muscular layers or serous layer of the stomach. The tubular branches look like polyps or look like a growing fungus under the microscope. It can cause necrosis and ulceration of the gastric mucosa and submucosa.

iii. Signet-Ring Gastric Adenocarcinoma:

The cells in this subtype of adenocarcinoma does not form connections with each other or do not interact. This phenomenon is called Poor Cohesion. The abnormal gastric cells have a large vacuole and these cells are called signet ring cells. The structure of these cells is like lymphocytes, plasma cells, and histiocytes. The cells form a gland-like structures that can produce mucin. Also, fibrous connective tissues grow around the tumor cells and this process is called Desmoplasia.

 iv. Mucinous Gastric Adenocarcinoma:

This adenocarcinoma subtype cells are normally found dispersed inside pools of mucin. The tumor cells can form glandular structures which clump together with a lot of mucin.

B. Squamous Cell Carcinoma of Stomach:

It is a very rare form of gastric cancer. It happens in the thin-flattened epithelial cells of the stomach called squamous epithelial cells. This kind of cancer is highly malignant and usually has a very bad prognosis. It normally happens at the point where the distal part of esophagus joins the stomach called Esophageal-gastric junction.

C. Mixed Cells Carcinoma:

This type of gastric cancer is made up of both glandular epithelial cells and squamous epithelial cells. This type of stomach cancer is known as Adenosquamous Carcinoma of the stomach. This kind of cancer mostly has a bad prognosis.

D. Lymphoma Of Stomach:

This kind of cancer normally affects the lymphatic system of the stomach. It is a very rare cancer type which affects the stomach. This type originates from the cells found in the lymph nodes of the stomach.

E. Carcinoid Tumors of the stomach:

This kind of tumors originate in cells that produce hormones in the stomach. This is a very rare type and not highly malignant. These tumors grow in a slow manner and they are known as neuroendocrine tumors. This because they contain secretory granules which respond to stimulation from the brain to secrete ectopic hormones.

F. Gastrointestinal Stromal Tumors (GIST):

This type of gastric cancer affects the cells that are situated in the outer space between the cells of the stomach. These cells are called the Interstitial Cells of Cajal. These cells provide motor innervation to the smooth muscles of the stomach and also stimulate the smooth muscles causing contraction. This is a rare type of gastric cancer and it is not always malignant.

 2. CLASSIFICATION BASED ON DEPTH OF CANCER GROWTH

1. Early Gastric Carcinoma:

This type of gastric cancer only occurs in the mucosal layer of the stomach. It sometimes may or may not invade the submucosal layer or lymph nodes of the Stomach. The tumor may invade lymph nodes or not. The tumor is mostly of a very small size accounting for its minor invasive action. It is grouped into subtypes according to the growth pattern of cancer.

A. Protruded Early Gastric Cancer:

This type of cancer grows on top of the mucous layer of the stomach and project into the cavity of the stomach.

B. Superficial Early Gastric Cancer:

This type of cancer is found on the upper part of the mucous membrane. But unlike the protruded type, it does not project into the gastric cavity. It is also grouped into three types.

• Superficial Flat:

This type is of the same level as the mucous membrane. It is not higher than the mucous membrane nor pushed down inside it.

• Superficial Elevated:

This type of Superficial early cancer of the stomach is slightly raised above the mucous membrane of the stomach but doesn’t protrude nor project into the gastric cavity.

• Superficial Depressed:

This type of cancer grows into the mucosal layer burying or sinking into it. The cancer is lower than the mucous membrane of the stomach.

C. Excavated Early Gastric Cancer:

This type of gastric cancer digs deep down and invade the submucosa layer of the stomach.

2. Advanced Gastric Carcinoma:

This type of cancer grows deeper than early cancers. As cancer progresses it invades the mucosal layer through to the serous layer of the stomach. It can penetrates or invade lymph nodes or not.

This type is also grouped into subtypes based on the growth pattern of cancer.

A. Single polyploid carcinoma:

This type of advanced cancer though it grows deep into the stomach layers, it also projects up into the cavity of the stomach. It is just like a gastric polyp.

B. Ulcerative Carcinoma with a clear margin:

This type of cancer wears out and ulcerate the layers of the stomach. The ulcerations in the layers of the stomach have well-defined borders with accurate demarcations.

C. Ulcerative Carcinoma with an unclear margin:

Cancer forms ulcerations in the gastric layers. The point in this type of cancers is that the ulcers have irregular and scattered margins without any appropriate demarcations.

D. Diffuse Advanced Carcinoma:

This type of cancer grows and infiltrate the layers of the stomach. It extends throughout the layers of the stomach where it is located and even extend beyond.

EPIDEMIOLOGY

Gastric or stomach cancer is one of the most common cancers in the world. It was the most frequently occurring type of cancer with the highest number of fatalities recorded before the 1980s.

In the United States, about 22,000 new cases of gastric cancer are recorded and an estimated number of people who died among the diagnosed cases is 11,000 in a year. In the United Kingdom, gastric cancer ranks as the 15th most common cancer with about 7000 new cases diagnosed in 2011. In terms of fatalities, it ranks as the 10th most common cancer in the United Kingdom with about 5000 fatalities recorded in the year 2011.
Stomach cancer caused the death of 13,300 people in the year 2014 with a percentage of about 0.6. In the world, gastric cancer is ranked as the 5th commonest cancer.

This is because, there was about 950,000 incidence of new cases of gastric cancer in the year 2012. It is recorded as the 4th most frequent and common cancer in men recording about 9% of all cancer-related cases among men. Generally, gastric cancer is more common in men than in women. About 700,000 fatalities were recorded in the year 2012 in favor of gastric cancer. This year gastric cancer was ranked as the third most deadly cancer in the world behind lung and liver cancers respectively.

Gastric cancer is very common in some parts of China like Mongolia where there were about 30 cases per every 100,000 people. About 325,000 people were recorded dead due to gastric cancer in China in the year 2014. This is about 3.6% making gastric cancer of a very high incidence and fatality rate in China.
In addition to this, Japan has a very high incidence of gastric cancer per year. It is stated that about 70 people out of 100,000 people’s are diagnosed with gastric cancer per year. Because it is common in Japan it is normally detected and managed early. About 50% of gastric cancers treated in Japan are early gastric cancers which are not allowed to reach their advanced stages.

Gastric cancer normally affects old people than young adults. The percentage of young people diagnosed with gastric cancer is about 5%. Out of this 5% about 80% affects people in their 40s and below and the remaining 20% affects people above age 20 onwards to 30.
The incidence rate of gastric cancer is very low as compared to that of other countries. Mali records about 0.3 to 100,000 people and Botswana records about 20.3 among 100,000.

CANCER RESEARCH BUDGET PER YEAR

A lot of money is generated and used in the funding of research programs into different forms of disease and cancers.

The incidences of cancers and the fatalities of cancers recorded per year scares the whole world and prompt attention is given to reducing it. Because of this, the American government generates money for effective research into these cancers in order to find new means of detection and diagnostic processes which will help in the accurate management of the cancers. When these tools are put in action they help reduce the frequency of occurrence of these cancers as well as the number of lives claimed per year by these malignancies.

In furtherance of this, different and specific types of cancers receive specific amounts of money for their research procedures. The total amount used for research by the National Cancer Institute of America from the years 2012 to 2017 is about 75 million US dollars.

The estimated average amount of money used per year for gastric cancer is about 12million US dollars. In totality, the National Institute of Health allocated an estimate of 5,600 billion US dollars for cancer research procedures only in the year 2017.

The determination of the amount of money that should be given into a particular kind of cancer for its research procedures is based on some these factors;

1. If the research into that particular cancer has the tendency to provide very useful clinically applicable results.
2. If the agency generating the money gets the findings which will in return make enough money out of the research being made.
3. If there is an already active and famous research already going on purposely for that kind of cancer.
4. If there is an already established organization which is solely working on the particular kind of cancer.
For these reasons stated above and others, not all type of cancers receives the same amount of funding for research. Even the funding process is not done blindly just because a particular cancer is of a high incidence and fatalities.

CAUSES OF GASTRIC CANCER

All cancers are caused due to mutations or alterations of genes that regulate and control the growth and proliferation as well as the death of old cells in the body.

To further elaborate on this, all cancers are caused due to genetic mutation notwithstanding the chief precipitating factor. Based on this, the two main forms of genetic mutation which affects tumor suppressor genes activities are;

1. Inherited mutations:

This type of mutations are called spontaneous mutations which occurs due to mutations in the sex cell or gamete producing cells (Germ Cells) during the formation of a baby. This type of mutations or gene defects is mostly taken from the parents. To add up, some of these mutations happen in intrauterine life but are not inherited from the parents because these mutations are not from germ cells. These mutations are called Acquired in intrauterine life mutations. This form of mutations affects the child mainly because of the things that happen to the mother or what she does during pregnancy.

2. Acquired Extrauterine life mutations:

These are mutations are obtained by a person based on the environmental influences. This kind of mutation is normally due to lifestyle, health conditions, and work. It is called Induced mutations.

PATHOPHYSIOLOGY

When the normal regulators of cell division, growth, and maturation are inactivated, the cell cycle goes wild and out of control.

Mutations that happen in genes that provide cell growth regulators is the main platform for cancer development. Tumor suppressor genes like p53 genes are inactive due to mutation and so oncogenic materials are able to cause cancers.

Mutations of the cells in the stomach result in cell division abnormally and rapid growth more than needed. These cells accumulate and refuse to die when they are supposed to mutation. These cells start growing more and bigger and invade nearby tissues of the stomach and spread to distant organs as well.

Helicobacter pylori infections that cause gastric ulcers is a very high ranked risk factor for developing gastric cancers.

Thus, when it becomes chronic and causes chronic inflammation to the stomach walls. This process of change of the epithelial cells of the stomach form normal to abnormal cancerous cells is called Correa Cycle. The mechanism in this cycle is caused mostly when the H.pylori is able to form a protein called Cytotoxin-associated gene protein A (Cag A).

This gene is able to interact with the intestinal cells and cause chronic gastritis which in turn will induce epithelial cellular changes and precancerous abnormalities.

The process in this cycle are;
1. Chronic inflammation and irritation of gastric cells of the stomach lining (Chronic gastritis).
2. Continuous Inflammation of gastric mucosal layer with depletion of glandular epithelium with fibrous tissues deposition (Atrophic gastritis).
3. Change and replacement of the glandular mucin epithelial cells of the stomach lining for columnar shaped intestinal goblet cells (Intestinal metaplasia).
4. Abnormal growth of the cells of the stomach which are precancerous(High-grade Dysplasia).
5. Cancerous cells or tumor that stays in a particular part of the stomach lining forms (Carcinoma In situ).
6. Cancerous cells that invade and spread to other tissues (Invasive or metastatic Carcinoma).

RISK FACTORS

1. Genetic factors; p53 gene mutations.
2. Family history of gastric cancer.
3. Persistent H.pylori infection (Cag A strains).
4. High salty and smoked fishes diet.
5. Autoimmune Gastric inflammations.
6. Diets that are low in fruits and vegetables.
7. Being male.
8. Chronic alcohol abuse.
9. Chronic smoking of tobacco products.
10. Being of old age.

CLINICAL MANIFESTATIONS 

1. Unexplained weight loss.
2. Loss of appetite.
3. Persistent fatigue.
4. Persistent Vomiting with or without blood.
5. Nausea.
6. Abdominal Pain.
7. Quick and easy satiety after eating a small amount of food.
8. Gastrointestinal bleeding.
9. Dark tarry stools are seen due to blood mixed in feces.
10. Anemia due to frequent loss of blood.

COMPLICATIONS OF GASTRIC CANCER

1. There can be Gastric perforations by invasive cancers.
2. There can be an infection in the large tumor cells which can cause peritonitis.
3. There is anxiety and stress caused by cancer.
4. Other body organs like the liver are affected due to the spread of cancer cells.
5. Destruction of vital organs like; nerves, blood vessels, and muscles by cancer and also surgical procedures.
6. Radiation therapy used for management, is poisonous to the body.
7. Infections caused due to the suppression of the bone marrow by chemotherapy.

PROGNOSIS

Just like all other cancers, gastric cancer outcome of treatment is dependent on the stage of diagnosis or detection.

Gastric cancer generally has a very poor prognosis due to the fact that they are mostly detected in very late stages either highly invasive and/or metastatic forms. The five-year survival rate for gastric cancer on the average is only about 5-10 %. Another reason why the prognosis of gastric is extremely poor is that, most of the cases are diagnosed in aged patients (70years and above).

The health status of these patients is generally low. Hence, treatment does not produce the expected effects. On the other hand, gastric cancers diagnosed in their early stages have a survival rate of about 95%. This is because non-invaded gastric cancers are easily managed by Surgery with a low probability of recurrence. As cancer invades deep into the submucosa and the muscular layers of the stomach, treatment becomes very difficult and almost ineffective.

Also, the prognosis becomes poorer. Metastatic gastric cancers are difficult to manage and the prognosis is very poor. Some of the prognostic factors of gastric cancer are; stage of cancer, the general health status of the person, type of cancer determined under a microscopic investigation, the age of the individual, the possibility of surgical intervention and overall response to treatment.

ROUTES OF METASTASIS OF GASTRIC CANCERS

1. Direct invasion or spread:

a) Cancer digs into the mucous layer, submucosa, muscular layer, and even the serous layer (horizontal invasion).

b) Cancer invades nearby organs like; colon, pancreas, and liver (vertical invasion).

2. Hematogenous spread:

Cancer Cells spread through blood primarily to the liver and then to other organs.

3. Lymphatic spread:

Cancerous cells penetrate and invade lymphatic vessels into lymph nodes found in the; sub-pyloric, gastric, pancreatic, duodenal, coeliac, aortic, left supraclavicular lymph nodes. These cancers mostly end up in the lungs and bone marrow.

4. Transperitoneal Spread:

Gastric cancers mostly spread through the peritoneal cavity after it has invaded into the serous membrane. It normally happens with fluid accumulation in the peritoneal cavity (ascites). These cancers can further invade other organs like the ovaries through the peritoneal cavity this is also called transcoelomic spread. Cancers in this stage are very advanced and are difficult to manage with very poor prognosis.

 STAGES OF GASTRIC CANCER

The staging of gastric cancer is very important and a key factor in deciding the management approach and prognosis. It also predicts the outcome of the disease most often before treatment is started. The TNM cancer staging system is used; the size of the tumor(T), number of lymph node invasion(N), and metastasis of the tumor(M).

1. Stage 0 (Tis, N0, M0): Abnormal cells are detected in the stomach lining. These abnormal or cancerous cells remain in the mucous membrane of the stomach alone with no lymph node invasion or distant spread. It is called cancer in its original place (Carcinoma In situ).

2. Stage 1

• Stage 1A(T1, N0, M0): Cancer size is growing bigger and invading the layers of the mucosal membrane, the lamina propria (loose connective tissue layer of the mucous), and muscular layer of the mucous layer. Cancer also invades the submucosa to some extent in this layer. There is no lymph node invasion or metastasis.

• Stage 1B(T2, N0, M0): Cancers in this stage invade the mucous, submucous, and muscular layer of the stomach with no lymph nodes invasion nor distant spread. The tumor size is bigger in this stage than before.

3. Stage 2
• Stage 2A(T2, N1, M0/T1, N2, M0/T3, N0, M0): This kind of cancer has invaded the muscular layer of the stomach and has spread to about 2 nearby lymph nodes. This cancer grows only to the extent of the submucous membrane and has spread to about 6 nearby lymph nodes. This cancer as well can be found growing into the subserous layer with no lymph node invasion. There is no distant metastasis in this stage.

• Stage 2B(T1, N3, M0,/T2, N2, M0/T3, N1, M0/T4, N0, M0): The cancerous cells have grown into the submucous membrane with about 15 neighboring lymph nodes invasion and no distant spread. Cancer can also be seen to have grown into the muscular layer with about 6 nearby lymph nodes. Also, cancer in this stage can grow into the layer beneath the serous layer with about 2 lymph nodes invasion and no spread to distant organs. Lastly, cancer can also grow into the serous layer of the stomach with no lymph node or distant spread.

4. Stage 3
• Stage 3A(T2, N3, M0/T3, N2, M0/T4a, N1, M0): Cancer in this stage has grown into the muscular layer with about 15 lymph node invasions and has no distant spread. Cancer in this stage is seen to have grown into the subserous layer with about 6 nearby lymph nodes invasion with no distant spread. Cancer cells have invaded the serous layer of the stomach and visceral peritoneal layer with about 2 nearby lymph nodes invasion with no distant spread.

• Stage 3B(T3, N3, M0/T4a, N2, M0/T4b, N2-N1, M0): Cancer has invaded the subserous layer with about 15 nearby lymph nodes invasion with no distant spread. Also, cancer in this stage has invaded the serous layer and the visceral peritoneum with about 6 lymph nodes invasion with no distant organ spread. Cancer in this stage has invaded the serous and visceral layers of the stomach and invaded adjacent structures to the stomach with about 6 to 15 lymph nodes invasion.

• Stage 3C(T4a, N3b, M0/T4b, N3a-N3b, M0): This cancer has invaded the entire stomach wall into the visceral layer of the peritoneum but it has not invaded nearby organs. It has invaded about 15 neighboring lymph nodes with no distant metastasis. In addition, this kind of cancers has invaded the serous and visceral layers with nearby organs invasion. It has also invaded about 16 nearby lymph nodes with no distant metastasis.

5. Stage 4(AnyT, AnyN, M1): This type of cancer has variant cell sizes with any number of lymph node invasions. The most recognizable and important feature of cancer at this stage is distant spread to organs like the liver, lungs, and bones. At this stage, the cancer is more aggressive and difficult to control by almost all treatment modalities. It is a systemic disease at this stage.

 

DIAGNOSIS OF GASTRIC CANCER

1. Gastrointestinal Endoscopy:

A a small camera called an endoscope is used to examine the stomach lining for the presence of abnormalities (ulcers, polyps, bleeders, etc).

2. Imaging Techniques:

CT-scan, Ultrasonography of the stomach, Contrast media X-ray (Barium enema or swallow), Positron Emission Tomography (PET).

3. Tissue biopsy:

A sample of stomach cells are taken for close examination in the lab.

4. Esophagogastroduodenoscopy (EGD):

A special endoscope is used to check for abnormalities in the esophagus, stomach, and duodenum.

5. Exploratory laparoscopy:

A minimally invasive surgical technique used to examine the stomach and other nearby organs for abnormalities. Samples can be also taken for biopsy studies in this process.

PREVENTION

1. Eat food with enough fruits and vegetables.
2. Quickly treat of H.pylori infections and check up to avoid the relapse of the infection.
3. Avoid tobacco smoking.
4. Avoid alcohol abuse.
5. Physical exercise to help maintain general health.
6. Reduce fat intake and eat balanced diets.
7. Maintain normal body weight.
8. People with a family history should do genetic testing and receive counseling.

TREATMENT OF GASTRIC CANCER

1. Surgery:

It is the main curative treatment for early detected gastric cancers.
• Partial or sub-total gastrectomy: A part of the stomach with surrounding lymph nodes are removed.
• Total gastrectomy: The whole organ is removed and the esophagus is joined to the intestines directly.

2. Chemotherapy:

Drugs are used both before and after surgical procedures to kill cancer cells and to prevent reoccurrence. When used before surgery it shrinks cancer cells so that cancer can be easily removed.

3. Radiotherapy:

High energy beam of light is used to kill cancer cells. The source of the light can be from outside the body (external radiotherapy) or inside the tumor cells (brachytherapy or internal radiotherapy)

4. Immunotherapy:

This procedures use drugs to enhance the body’s own immune cells to target and kill cancer cells. This is also called biological therapy.

5. Targeted therapy:

This is the use of drugs to target and destroy the features which allow cancerous cells to grow rapidly without control and also refuse to die. These drugs can arrest the cancer cells cycle and prevent their proliferation. Examples; Imatinib and trastuzumab.