Gastric Carcinoma

Gastric Carcinoma

Gastric cancer has been between the second and fourth most frequent cancer worldwide for the last decade. A gastric carcinoma is a malignant tumor arising from the epithelium of the stomach. More than 90% of stomach cancers are adenocarcinomas. Non-Hodgkin lymphomas can be found in the muscles of the stomach. Carcinoid tumors can also occur in the stomach

Epidemiology

Gastric cancer is the seventh leading cause of cancer deaths. Gastric cancer is the third most common gastrointestinal malignancy in North America. The frequency of this disease varies hugely across different geographic locations.This form of gastric cancer is very common in Japan, Chile, and Iceland. Gastric cancer is responsible for 3% to 10% of all deaths due to cancer. Gastric cancer usually occurs after the age of 40. Worldwide, however, gastric cancer rates are about twice as high in men as in women. Gastric cancer is second to lung cancer in terms of mortality rate.

The sub-types of Gastric carcinoma

The Gastric adenocarcinomas can be classified under the following types:

1) Type 1: Intestinal type

  • Cohesive neoplastic cells forming gland like tubular structures.
  • Mostly ulcerative, occur in the distal stomach
  • Environmental association found
  • More common in males

2) Type 2: Diffuse type

  • Individual cells infiltrate and thicken the stomach wall without forming a discrete mass.
  • Develop throughout the stomach but especially in the cardia
  • Prognosis is worse than intestinal type.
  1. Etiology or Risk factorsChronic inflammation, exposure to diverse carcinogens, and genetic susceptibility are among factors associated with an increased risk of gastric cancer. The following factors are responsible for gastric carcinoma:Helicobacter pylori infection, chronic gastritis, intestinal metaplasia and ulcer

    Helicobacter pylori are bacteria that can survive and grow in the stomach. Chronic infection due to this bacterium can be a cause of gastric adenocarcinoma. A rare B cell tumor called MALT lymphoma may also develop in infected patients.

    H. pylori induced gastric carcinoma can be due to several factors. The exact mechanism is not yet certain. However, scientists believe that certain strains of these bacteria can secrete a virulent protein called Cag A in the gastric epithelial cells. Changes brought about by this protein may lead to gastric carcinoma. Another reason may be that prolonged infection leads to inflammation of the gastric mucosa, where a continuous secretion of some chemical messengers called cytokines takes place. These cytokines when present consistently for a long time can be a cause of cancer. H. pylori has been classified as a Group I carcinogen by the World Health Organization (WHO).

    Further, many cases of chronic gastritis caused due to H. pylori infection may lead to gastric carcinoma. Chronic gastritis may be of two types: atrophic and non-atrophic. Intestinal metaplasia, which develops as a result of chronic atrophic gastritis, increases the chances of gastric carcinoma significantly. But, studies suggest the extent of atrophic gastritis is a better indicator of gastric cancer risk than the detection of intestinal metaplasia.

    Gastric ulcers induced by H. pylori infection also show a moderate correlation with gastric carcinoma.

    Epstein-Barr virus (EBV) infection

    Epstein-Barr virus (EBV) is a virus that has been linked with gastric cancer. The mechanisms associated are not revealed yet. While most people have been infected with this virus by adulthood, few develop cancer.

    Dietary and Lifestyle Factors

    Polycyclic aromatic hydrocarbons present in smoked foods can be a cause of cancer. Irritation in stomach caused by salt damages the gastric mucosa which can lead to gastric cancer. N-nitroso compounds formed from nitrated foods are also a carcinogen. H. pylori can cause the conversion. Therefore, risk of cancer can be reduced by low intake of smoked, salted and nitrated foods.

    It is believed that much of the regional variation of rates of stomach cancer is due to these kinds of dietary factors, and that changes in diet can lower the risk of cancer.

    High intake of fruit and vegetables reduces the risk of developing stomach cancer significantly.

    Smokers have a high chance of developing gastric carcinoma. Gastric cancer cell proliferation is accelerated by cigarette smoke. Alcohol consumption is weakly correlated with gastric carcinoma.

    Exposure to ionizing radiation, organic and inorganic dusts, nitrate and nitrogen oxide precursors, leaded gasoline, crystalline silica, glycol ethers and hydraulic fluids in the work place have been suggested as occupational risk factors.

    Family history and Genetic polymorphisms

    8-10% of gastric cancer cases have been related to familial history. Although most gastric carcinomas arise sporadically, history of gastric carcinoma in the family can increase the risk of the disease.

    Type A blood group

    Gastric carcinomas and the blood group A have been correlated in a number of studies. The Lewisb blood group antigen and H.pylori interacts with each other leading to such complications.

    Previous gastric surgery

    Previous surgery is implicated as a risk factor. This is because the normal pH of the stomach changes, which may in cause metaplastic and dysplastic changes in luminal cells. Gastric polyp removal also causes cancer in some cases.

    Inherited cancer

    Hereditary Diffuse Gastric Cancer (HDGC): HDGC is an autosomal dominant inheritable disease, usually developing at an early age. It occurs due to germline mutations in the E-cadherin (CDH1) gene. Methylation of the promoter of this gene can also be the cause of gastric cancer. These are diffuse, poorly differentiated adenocarcinomas with an infiltrative growth pattern.

    Hereditary non-polyposis colorectal cancer (HNPCC) is also a risk factor for stomach cancer.

    Other risk factors:

    Pernicious anemia

    Menetrier disease (giant hypertrophic gastritis)

    Clinical presentation or Symptoms

    Most symptoms appear when the disease has advanced to a certain stage. Patients may complain of the following:

    1) Abdominal pain, from vague to severe

    2) Indigestion, heartburn, and vomiting

    3) Difficulty in swallowing

    4) Postprandial bloating

    5) Loss of appetite

    6) Black tarry feces (related to gastrointestinal bleeding)

    7) Hematemesis (related to gastrointestinal bleeding)

    8) Weight loss

    Symptoms at an advanced stage may be:

    1) Pleural effusions

    2) Gastric outlet obstruction

    3) Bleeding due to a number of causes

    4) Jaundice

    5) Cachexia of tumor origin, which means severe weight loss

    Diagnosis and Staging

    Physical exam: The doctor checks whether there is any abnormal swellings in the abdomen.

    Endoscopy: Endoscopy is the most sensitive diagnostic method for detecting gastric cancer. When combined with endoscopy and radiologic modalities, endoscopic ultrasound (EUS) can provide more information about depth of tumor invasion and evaluate the invasion of cancer into the lymph nodes.

    Imaging techniques: T staging can be studied with the help of MRI and CT scanning techniques. Other staging modalities include abdominal ultrasound and positron emission tomography scans.

    Biopsy: Tissue or cells removed from the tumor can be examined under a microscope in the laboratory for detecting malignancy.

    Treatment

    Surgery

    Surgery is the foremost treatment for localized gastric carcinoma. A partial or total gastrectomy depending on the size and location of the tumor with an embolic lymph node dissection is the standard treatment.

    Chemotherapy and Radiotherapy (adjuvant and neoadjuvant therapies)

    Chemotherapy or radiotherapy or their combination of the two can be used before (neoadjuvant) or after (adjuvant) the surgery (mainstay treatment).

    Chemotherapy has been shown to reduce the progress of the disease and increase survival in gastric cancer patients. Fluorouracil, cisplatin, doxorubicin and methotrexate are some of the chemotherapeutic agents used to treat this disease. Usually the drugs are used in combinations.

    New drugs targeted at the cells, like irinotecan, oxaliplatin and taxanes have provided better results in the metastatic setting.

    Patients with positive human epidermal growth factor receptor 2 (HER2) status, which is associated with increased aggressiveness and worse prognosis can be treated with trastuzumab in addition to the standard use of fluoropyrimidine and cisplatin.

    Radiotherapy may also be used to treat gastric carcinoma.

    Recently it has been shown in three trials: the American INT 0116 trial (adjuvant chemoradiation therapy); the European MAGIC trial, (perioperative combination chemotherapy) and the Japanese ACTS-GC trial (adjuvant monotherapy) that patients receiving adjuvant treatments show better rate of survival over surgery only.

    Prognosis

    The main prognosis is based on TNM staging (tumor stage, nodal stage and metastasis) and the presence and extent of lymph node metastases.

    Patients with localized tumors may have a five-year survival rate of 57% to 71% or even higher with new treatments. Those with advanced cancer have a five-year survival rate of only 4%.

    It is important to try and diagnose this cancer earlier, as well as use all possible means to lower risk factors.

    References

    1. Gastric Carcinoma – Molecular Aspects and Current Advances (2011) Ed. Dr. Mahmoud Lotfy, Publisher: InTech
    2. Sano T (2008) Adjuvant and neoadjuvant therapy of gastric cancer: a comparison of three pivotal studies. Curr Oncol Rep. ;10(3):191-8.
    3. Kelsen DP (1996) Adjuvant and neoadjuvant therapy for gastric cancer. Semin Oncol.; 23(3): 379-89.
    4. Stacy Carl-McGrath, Matthias Ebert and Christoph Röcken (2007) Gastric adenocarcinoma: epidemiology, pathology and pathogenesis. Cancer Therapy; 5: 877-894.
    5. Gastric Adenocarcinoma: Review and Considerations for Future Directions (2005) Dicken BJ, Bigam DL, Cass C, Mackey JR, Joy AA, Hamilton SM. Ann Surg. ; 241(1): 27–39.
    6. Khan FA, Shukla AN (2006) Pathogenesis and treatment of gastric carcinoma: “an up-date with brief review”. J Cancer Res Ther.;2(4): 196-9.
    7. American Cancer Society.: Cancer Facts and Figures 2010. Atlanta, Ga: American Cancer Society, 2010.
    8. This article was originally published on September 3, 2012 and last revision and update was 9/4/2015.