Cancer Of The Stomach Biology Essay

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The stomach is a hollow,muscular organ just below the diaphragm that stores the food during eating, secretes digestive juice, mixes food with these juices, and propels partially digested food , called chime into the duodenum of the small intestine. Its major anatomic boundaries are the lower esophageal sphincter where food passess through the cardiac orifice into the stomach, greater and lesser curvatures, and the pyloric sphincter, which relaxes as food is propelled through the pylorus into the duodenum. Functional areas are the fundus, body and antrum.

Gastric motility increases with the initiations of peristaltic waves. The rate of peristaltic contractions is influenced by neural an hormonal activity

Due to eating stimulation, the stomach secretes large volumes of gastric juices including mucus, acid, enzymes,hormones, intrinsic factor and gastroferrin.

(Sue & Kathryn, 2008)

Terminology Of The Stomach Cancer

Cancer of the stomach is also known as stomach carcinoma or gastric carcinoma/cancer.

Adenocarcinoma is the most significant malignant tumor of the stomach and accounts for 97% of all malignant lesions in the stomach. This name implies that the cancer is located in the stomach (gastric), affects cells that would normally make up glands (adeno-) and has malignant potential (-carcinoma). Other forms of stomach cancer include lymphomas, which involve the lymphatic system and sarcomas, which involve the connective tissue (such as muscle, fat, or blood vessels).

Morphologically, gastric carcinoma is classified into four distinct types: (1) the fungating or polypoid type, which has the best prognosis; (2) the ulcerating type, which arises as growth away from the lumen and may be confused with a benign ulcer; it appears in the early life of the cancer and is the most common type of cancer, accounting for 30% of all the stomach cancers; (3) the superficial spreading type; and (4) a diffuse spreading type referred to as linitis plastic/ scirrhous carcinoma, which accounts for 10% of all gastric carcinomas. It is common for the diffuse type to infiltrate the walls before the layers bulge into the lumen. The involved part becomes contracted, thick-walled, and firm. It begins and encircles the pylorus and causes obstruction. The prognosis is extremely poor, and cure is rare because of the early disease advancement prior to detection. Gastric carcinoma metastasizes very early to the liver and other organ and structures including the lungs and bone. Metastases grow in the liver, and emboli are discharged and spread via the portal venous system to the lungs and eventually to the bone. . (PATHO FOR JXR,89)

Histologically, gastric cancers tend to fall into one of two types (Lauren Classification) : (1) intestinal, malignant cells arranged in acini invade through the muscle of the stomach wall ; (2) diffuse, typically seen in linitis plastic. These tumors consist of signet ring cells. Extracellular mucin may also be present. Globules of mucin push the nucleus to one side . (robin & Fiona)

Gastric carcinomas are aggressive tumors with both local and distant spread. Local spread to oesophagus, mucosal and submucosal lymphatic spread to duodenum, to draining lymph nodes, to adjacent viscera including liver. Distant spread by lymphatics to supraclavicular node, to lungs but usually to late, hematogenous to liver via portal vein and transcoelomic to ovaries. (robin & Fiona)



2.1 Causes

Helicobacter pylori infection is believed to be the cause of most stomach cancer while various genetic factors and autoimmune atrophic gastritis, intestinal metaplasia are associated with increased level of risks. Smoked foods, salted fish and meat, and pickled vegetables appear to increase the risk of stomach cancer. Nitrates and nitrites are found in cured meats. They can be converted by certain bacteria, such as into compounds that have been found to cause stomach cancer in animals.. In more detail, H. pylori are the main risk factor in 65-80% of gastric cancers, causes mechanism in which it induces stomach cancer potentially involves virulence factor or chroni inflammation.

Tobacco smoking is a very important but preventable cause of gastric cancer. 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. Alcohol and tobacco consumption are risk factors for the disease.

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.

2.2 Incidence

Stomach cancer is an important cause of death among patients with malignancies in Malaysia and ranked as the seventh most common cancer in males in Peninsular Malaysia and tenth among females pdf. Adenocarcinomas formed the majority (72.3%) of stomach cancers in Malaysia. Pdf.

The Malaysian National Cancer Registry (NCR) report for the period 2003-2005 shows an incidence of stomach cancer of 2.2 for Malay, 11.3 for Chinese and 11.9 for Indian males per 100,000 population. Malay (1.3), Chinese (7.2) and Indian (7.2) women have rates lower than men. Malays in Peninsular Malaysia have five times less stomach cancer than Chinese and Indians. This racial difference is more marked than that noted in the Singapore cancer registry. Regional data from Kelantan has an even lower rate for Malays there (1.5 for males and 0.9 for females per 100,000 population). The incidence of Helicobacter pylori infection, a known risk factor for stomach cancer, is low among Malays.

Gastric cancer incidence varies markedly with geography. In Japan, Chile, Costa Rica, and Eastern Europe, the incidence is up to 20-fold higher than in North America, northern Europe, Africa and Southeast Asia. Mass endoscopic screening programs can be successful in regions where the incidence is high, such as Japan, where 35% of newly detected cases are early gastric cancer, tumors limited to the mucosa and submucosa. Unfortunately, mass screening programs are not cost effective in regions where the incidence is low. And fewer than 20% of cases are detected at an early stage in North America and northern Europe. In the United States, gastric cancer rates dropped by over 85% during the twentieth century.

figure stomach cancer international comparisons

2.3 Mortality & Morbidity

This very important malignant tumor has an especially high incidence in Japan, Chile and Italy. Its incidence has fallen in the United Kingdom and the U.S.A. since the 1930s.

Gastric cancer is still the second most common fatal malignancy after lung cancer in the world, with an estimated three quarters of a million new cases diagnosed annually.

Adenocarcinoma of the stomach was the common cause of cancer death in the united states in 1930 and remains a leading cause of cancer death worldwide, but now accounts for fewer than 2.5% of cancer deaths in the United States .The age specific incidence curve increased exponentially with age. The sharp rise occurred after 60 years of age. The difference between the age specific incidence curve in males and females widened with increasing age. Survival of patients with gastric cancer is dependent on the stage at which diagnosis is made.

2.4 Signs And Symptoms

Stomach cancer in early stages often produce no noticeable symptoms (asymptomatic) or symptoms which are not specific to just stomach cancer (non specific symptoms), but also to other related or unrelated disorders. The cancer has often reached an advanced stage which may also metastasized and induced poor prognosis by the time the noticeable symptoms occur. (Internet ca 1)

Table : signs and symptoms of stomach cancer

Stage 1 ( Early)

Stage 2 (Middle)

Stage 3 (Late)

Indigestion , heartburn

which produces burning sensation

Appetite loss especially for meat

Irritation or abdominal discomfort

Fatigue and weakness

Bloating of the stomach usually after meals

Upper abdominal pain

Occasional vomiting and nausea

Constipation or diarrhea

Loss of weight

Blood present in vomitus referred to as hematemesis. This hemorrhage is usually from the stomach

Melena, the passage of dark, tarry stools


Dysphagia, this feature suggests a tumor in the cardia or extension of the gastric tumor in to the esophagus

2.5 Pathophysiology

H.pylori has now been accepted as the major of chronic gastritis, it is logical to implicate this infection in the causation of gastric cancer. The prevalence of H.pylori infection frequently runs parallel with the incidence of gastric cancer in the same populations. Long-term infection leads to glandular atrophy which leads to a gradual decline in acid secretion. Hypochlorhydria allows other bacteria to proliferate in the gastric juice; these bacteria are capable of reducing nitrate ions to nitrite and can catalyse nitrosation of amines and amides present in the diet to give rise to potentially carcinogenic compounds.

H.pylori is capable of producing acetaldehyde. Acetaldehyde is a highly reactive product which damages epithelial cells and can cause DNA damage and can be minimized by anti-oxidant vitamins. Diets rich in fresh fruits and vegetables as protective against gastric cancer.

The most important factor underlying the relationship between H.pylori and gastric cancer is a promotional effect through high cell turnover. The production of cytotoxins and ammonia by the organism, and indirect epithelial damage brought about by cytokines and polymorph products, induce increased cell turnover. DNA repair is compromised by increased cell proliferation,and the probability of a mutation escaping repair and being transmitted to daughter cells is increased.

Several molecular genetic changes have been demonstrated in gastric cancer. Mutations and deletions of tumor surpressor genes have been

However while some of these mutations are consistent with exogenous chemical carcinogens or exposure to endogenous free radical injury, one cannot infer the nature of the mutational agent from the genetic lesions with any certainty. Nevertheless the overall evidence favours link between H.pylori infection and gastric cancer.

2.6 Histopathology

Gastric adenocarcinomas are classified according to their location in the stomach.gastric cancer with diffuse infiltrative growth pattern are more often composed of signet ring cells. Although intestinal type adenocarcinomas may penetrate the gastric wall, they typically grow along broad cohesive fronts to form either an exophytic mass or an ulcerated tumor. The neoplastic cells often contain apical mucin vacuoles, and abundant mucin may be present in the gland lumens. In contrast, diffuse gastric cancer is generally composed of discohesive cells that do not form glands but instead have large mucin vacuoles that expand the cytoplasm and push the nucleus to the periphery, creating a signet-ring cell morphology. These cells permeate the mucosa and stomach wall individually or in small clusters, which makes tumor cells easy to confuse with inflammatory cells, such as macrophages,at low magnification. Extracellular mucin release in either type of gastric cancer can result in formation of large mucin lakes that dissect tissue planes. Kumar ababss

A mass may be difficult to appreciate in diffuse gastric cancer, but these infiltrative tumors often evoke a demoplastic reaction that stiffens the gastric wall and may provide a valuable diagnostic clue. When there are large areas of infiltration diffuse rugal thickening and a rigid, thickened wall may impart a leather bottle appearance termed linitis plastic. Breast and lung cancers that metastasize to the stomach may also create a linitis plastic-like appearance Kumar ababss

Figure Gastric signet ring cell carcinoma.

Figure Adenocarcinoma of the stomach and intestinal metaplasia.

2.7 Staging

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:[19][20]

Stage 0. Limited to the inner lining of the stomach. Treatable by endoscopic mucosal resection when found very early (in routine screenings); otherwise by gastrectomy and lymphadenectomy without need for chemotherapy or radiation.

Stage I. Penetration to the second or third layers of the stomach (Stage 1A) or to the second layer and nearby lymph nodes (Stage 1B). Stage 1A is treated by surgery, including removal of the omentum. Stage 1B may be treated with chemotherapy (5-fluorouracil) and radiation therapy.

Stage II. Penetration to the second layer and more distant lymph nodes, or the third layer and only nearby lymph nodes, or all four layers but not the lymph nodes. Treated as for Stage I, sometimes with additional neoadjuvant chemotherapy.

Stage III. Penetration to the third layer and more distant lymph nodes, or penetration to the fourth layer and either nearby tissues or nearby or more distant lymph nodes. Treated as for Stage II; a cure is still possible in some cases.

Stage IV. Cancer has spread to nearby tissues and more distant lymph nodes, or has metastatized to other organs. A cure is very rarely possible at this stage. Some other techniques to prolong life or improve symptoms are used, including laser treatment, surgery, and/or stents to keep the digestive tract open, and chemotherapy by drugs such as 5-fluorouracil, cisplatin, epirubicin, etoposide,docetaxel, oxaliplatin,



3.1 Upper GI Series

Radiography has limited diagnostic value in the diagnosis of gastric cancer. Although it suggests a high sensitivity of x-rays (80-95%), there are limitations. Upper gastrointestinal series may show thickened or enlarged gastric folds, filling defects that correspond to a mass or ulcer, or may demonstrate a failure of the stomach to distend normally to air and instilled barium but do not aid in accurate disease staging and do not allow differentiation of benign from malignant lesions

3.2 Endoscopy

It provides the most specific and sensitive means of diagnosis of gastric cancers. Gastrointestinal endoscopy allows the physician to visualize and biopsy the mucosa of the esophagus, stomach, duodenum, and most of the jejunum.

During these procedures, the patient is situated in the left lateral position and may be administered a topical anesthetic to help prevent gagging. Pain medication and a sedative may also be administered prior to the procedure.

The endoscope (a thin, flexible, lighted tube) is passed through the mouth and pharynx and into the esophagus. It transmits an image of the esophagus, stomach, and duodenum to a monitor visible to the physician. Air may be introduced into the stomach through the scope to expand the folds of tissue and enhance examination (Figure 14).

More than 90% of gastric cancers are detected by upper endoscopy and biopsy. Endoscopy facilitates accurate visualization, histological confirmation and typing. Tumor staging, localization and extent of tumor, and associated local complications may also be established during the procedure (Figure 15).   

In cases of known gastric cancer, endoscopy is helpful to establish treatment goals (cure or palliation), TNM stage, and assessment of response to previous therapeutic approaches. Biopsy leads to correct diagnosis in virtually 100% of cases when at least 7 specimens are obtained. The increasing use of endoscopy has resulted in detection of "early gastric cancer", which is amenable to endoscopic therapy.

3.3 Computed Tomography(CT)

CT is used preoperatively primarily to determine the stage and extragastric spread of a gastric carcinoma. This information is vital in deciding between palliative surgery and curative radical surgery Additionally, CT is used to monitor a patient's response to treatment.

CT scans may show polypoidal mass with or without ulceration, focal wall thickening with mucosal irregularity or ulceration or infiltrative lesions, marked contrast enhancement, mucinous carcinomas, which have low attenuation due to their high mucin content and which may contain calcification.

CT scanning has several pitfalls: A pseudomass as a result of a normal gastroesophageal junction may be seen, underdistension of the stomach may simulate wall thickening, and T2 and T3 lesions may be difficult to distinguish. CT may fail to depict tiny omental and peritoneal deposits; small pelvic deposits may be overlooked as well.

3.4 Magnetic Resonance Imaging

MRI studies in which a breath-hold, fast-imaging technique and water were used showed accuracy rates comparable to those of helical, biphasic CT scanning. The fast-imaging technique was superior to CT in detecting serosal invasion.

In T staging, the accuracy of MRI is 73%, compared with 67% for CT. In N staging, the accuracy of MRI is 55%, compared with 59% for CT.

MRI is limited by the presence of respiratory and peristaltic artifacts, the lack of suitable oral contrast media, and a higher cost than that of CT scanning.

3.5 Ultrasonography

The primary role of transabdominal ultrasonography (US) is to detect liver metastases. CT scanning is used first to stage the gastric carcinoma; if no metastases and no invasion of local organs are found, US is used to refine the local stage. The depth of tumor invasion is not accurately assessed with CT, and the investigation of choice for this indication is EUS.[2]

Gastric carcinomas are occasionally identified during US of the upper abdomen.US has improved the accuracy of local staging of gastric carcinomas. Its role is to assess the depth of local invasion and the presence or absence of perigastric nodes. Unlike CT and MRI, US can depict individual layers of the gastric wall. Diagnostic accuracy, In the detection of liver metastases, sensitivities as high as 85% have been reported.

Overstaging is due to the peritumoral inflammatory response.

In T staging, EUS is 89-92% accurate, and CT is 43-65% accurate; however, the accuracy of CT increases with the use of the helical biphasic technique. In N staging, EUS is 60-85% accurate, and CT is 48-70% accurate. Inflammation may cause enlarged nodes. EUS has a high specificity (90%) but low sensitivity (53-80%) because it has a range of 5 cm from the gastric wall for nodes of normal size; thus, it does not permit assessment of the full extent of lymphadenopathy. Involved small nodes are not detected.

Intraoperative US and laparoscopy have an accuracy of 81% in T staging and an accuracy of 93% in N staging; however, the necessary equipment and expertise are not widely available.

3.6 Nuclear Imaging

Fluorodeoxyglucose (FDG) positron-emission tomography (PET) scanning may be useful in the staging and postoperative assessment of gastric carcinomas. FDG-PET depicts the primary tumor, but involved perigastric lymph nodes are not identified separately from the primary tumor. Thus, the role of PET scanning is limited in staging. The use of combined PET-CT scanning may improve diagnostic accuracy.

Indium-111 (111 In) - labeled monoclonal antibody has been used for intraoperative imaging to detect nodes, with an accuracy of 72%.

FDG-PET may be useful in evaluating patients with recurrent gastric cancer; findings can help to localize the disease when CT findings are not diagnostic. Imaging evaluation with PET may also impact the clinical management of patients with recurrent gastric cancer.



Figure :This is a case of diffuse gastric adenocarcinoma (Lauren classification) presenting surgically as 'linitis plastica' (leather bottle stomach). Microscopic regional lymph node metastases were present.

Figure :Endoscopic view of an ulcerating adenocarcinoma

irregular stenosis with rigidity of the greater curvature of the stomach at prepyloric gastric antrum

Figure Barium irregular stenosis with rigidity of the greater curvature of the stomach at prepyloric gastric antrum

C:\Users\User\Desktop\internet\Gastric carcinoma Radiology Case Radiopaedia.org_files\5cc80d5d4fbcd283844c8784f3912e_big_gallery.jpg

Figure Double contrast images from a barium meal study showing an advanced gastric malignancy involving the body of stomach.

C:\Users\User\Desktop\internet\Gastric adenocarcinoma Radiology Case image_files\3db086d7a30cdca2b17b441c89a97a_big_gallery.jpg

Figure Large stomach adenocarcinoma, with heaped up edges and central ulceration, which is a feature of up to 70% of gastric adenocarcinomas.

Figure CT image showing gastric cancer

Figure : Stomach wall thickening with loss of gut signature sign is noted along lesser curvature. Stomach wall thickening with loss of gut signature sign is noted along lesser curvature.

C:\Users\User\Desktop\internet\Gastric cancer Radiology Case image_files\77015a432f84ff9f9afb9d3b348501_big_gallery.jpg

Figure : Abdomen CT demonstrates a subtle circumferential wall thickening involving the gastric cardia and gastroesophageal junction. High FDG uptake is noted at the gastric cardia confirm the presence of the tumour.





6.1 Treatments

6.1.1 Surgery

Endoscopic mucosal resection is a treatment for early gastric cancer removing tumor in the mucosa together with the inner lining of stomach from the wall of stomach using an electrical wire loop through the endoscope. It is a much smaller operation than removing the stomach thus advantageous, pioneered in Japan and also available in the United States.

Endoscopic submucosal dissection is also pioneered in Japan by using similar technique, resecting a large area of mucosa in one piece. The patient would need a formal stomach resection if the pathologic examination of the resected specimen shows incomplete resection or deep invasion by tumor.( Internet ca 1)

Other than that, a radical subtotal gastrectomy is usually the initial treatment of choice. This procedure involves the surgical removal of a large part of the stomach. It is indicated for gastric ulcers, which have a significant predisposition for eventually developing into cancer. At the same time, the surgeon may remove the spleen and resect the associated lymph nodes. Reconstruction is accomplished by a gastrojejunostomy or gastroduodenostomy. The remaining part of the stomach is anastomosed onto that of the jejunum. One of the more common procedures is the Billroth I or Billroth II gastrojejunostomy. Surgical interventions are currently curative in less than 40% of cases, and, may be palliative in cases of metastasis. (PATHO FOR JXR,89

6.1.2 Chemotherapy

Chemotherapy has no firmly established standard of care in treating stomach cancer. Stomach cancer has not been particularly sensitive to chemotherapy drugs and usually it serves to palliatively decrease the tumor size, relieve symptoms of the disease and increase survival rate. Clinical researchers have discovered the advantages of undergoing chemotherapy prior surgery to shrink the tumor, or as adjuvant therapy post surgery to destroy remaining cancer cells. .( Internet ca 1) thus far, chemotherapy has been somewhat successful when administered postoperatively or in cases that are inoperable. (PATHO FOR JXR,89)

6.1.3 Radiation Therapy

The usage of high-energy rays to destroy cancerous cells and stop their growth is how radiation therapy works. It is generally in combination with surgery and chemotherapy or only being used 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. .( Internet ca 1) relieve pain As a rule, radiation therapy is not effective in the treatment of gastric carcinoma. The therapeutic radiation dose is quite high, the tolerance level would be reached very fast and the side effects would be significant. Carcinoma of the stomach recurs in 50% to 80% of persons who have had a previous gastrectomy. Radiation therapy is usually administered after the second resection. (PATHO FOR JXR,89)


Most stomach cancers are advanced when they are diagnosed. Only about 20 out of 100 people are able to have surgery to try to cure their cancer. In the UK, overall about 15 out of every 100 people diagnosed (15%) live for at least 5 years. About 11 out of every 100 people diagnosed (11%) live for at least 10 years. Younger people tend to have longer survival compared to older people. In people aged under 50, between 16 to 22 out of 100 (16 to 22%) will live for more than 5 years compared to 5 to 12 out of 100 (5 to 12%) in people over 70. Some American studies have also shown that Asian people have better survival after stomach cancer treatment than people from other ethnic groups.

Prognosis for the different stages of stomach cancer:

Stage one

For stage one stomach cancers, about 8 out of 10 people (80%) live for at least 5 years after they are diagnosed. Unfortunately, very few people are diagnosed this early - probably only about 1 in 100 cases of stomach cancer are stage 1.

Stage two

About 6 out of every 100 stomach cancers are stage two when they are diagnosed. With a stage 2 cancer, more than 5 out of 10 people diagnosed (56%) will live at least 5 years.

Stage three

Stage three stomach cancers are slightly more common still. About 1 in 7 people are stage 3 at diagnosis. As you might expect, the survival statistics fall with this more advanced stage of cancer. With stage 3A stomach cancer about a third of people (38%) live at least 5 years. With stage 3B about 1 in 6 people (15%) live for more than 5 years.

Stage four

Unfortunately, about 8 out of 10 (80%) people diagnosed with stomach cancer are stage four, meaning the cancer has already spread when they are diagnosed. Understandably, the survival statistics are lower than for stage 3 stomach cancers. Doctors generally think a patient is doing very well if they are still alive two years after being diagnosed with stomach cancer that has spread. Fewer than 1 in 20 people (5%) live for at least 5 years if they have stage 4 stomach cancer when they are diagnosed.

The prognosis of gastric carcinoma is related to the stage of the disease at the time of diagnosis and to the histologic grade of the carcinoma.[1]

Pathologic staging of these neoplasms is based on tumor stage, nodal stage, and metastasis stage (TNM). The stages are as follows:

The T stage, representing the extent of penetration through the gastric wall, is categorized as follows:

Tis - Carcinoma in situ, intraepithelial tumor

T1 - Tumor extension to submucosa

T2 - Tumor extension to the muscularis propria or subserosa

T3 - Tumor penetration of the serosa

T4 - Tumor invasion of the adjacent organs

The N stage, representing the number and site of draining lymph nodes involved, is categorized as follows:

N0 - No lymph nodes involved

N1 - Metastases in 1-6 regional lymph nodes

N2 - Metastases in 7-15 regional lymph nodes

N3 - Metastases in >15 regional lymph nodes

The M stage, representing the presence of metastases, is categorized as follows:

M0 - No distant metastases

M1 - Distant metastases

Table : Staging and 5-Year survival rates


TNM Stage

5-Year Survival


T1N0M0, T1N1M0, or T2N0M0



T1N2M0, T2N1M0, or T3N0M0



T2N2M0, T3N1M0, or T4N0M0






T4N1-3M0, TxN3M0, or TxNxM1*


*Tx indicates any T stage; Nx, any N stage.