Gastric Cancer Clinical Presentation

  • Author: Elwyn C Cabebe, MD; Chief Editor: Jules E Harris, MD   more...
 
Updated: Mar 2, 2012
 

History

In the United States, about 25% of stomach cancer patients present with localized disease, 31% present with regional disease, and 32% present with distant metastatic disease; the remainder of cases surveyed were listed as unstaged.

Early disease has no associated symptoms; however, some patients with incidental complaints are diagnosed with early gastric cancer. Most symptoms of gastric cancer reflect advanced disease. Patients may complain of indigestion, nausea or vomiting, dysphagia, postprandial fullness, loss of appetite, melena, hematemesis, and weight loss.

Late complications include pathologic peritoneal and pleural effusions; obstruction of the gastric outlet, gastroesophageal junction, or small bowel; bleeding in the stomach from esophageal varices or at the anastomosis after surgery; intrahepatic jaundice caused by hepatomegaly; extrahepatic jaundice; and inanition resulting from starvation or cachexia of tumor origin.

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Physical

All physical signs are late events. By the time they develop, the disease is almost invariably too far advanced for curative procedures.

Signs may include a palpable enlarged stomach with succussion splash; hepatomegaly; periumbilical metastasis (Sister Mary Joseph nodule); and enlarged lymph nodes such as Virchow nodes (ie, left supraclavicular) and Irish node (anterior axillary). Blumer shelf (ie, shelflike tumor of the anterior rectal wall) may also be present. Some patients experience weight loss, and others may present with melena or pallor from anemia.

Paraneoplastic syndromes such as dermatomyositis, acanthosis nigricans, and circinate erythemas are poor prognostic features.

Other associated abnormalities also include peripheral thrombophlebitis and microangiopathic hemolytic anemia.

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Causes

Gastric cancer may often be multifactorial, involving both inherited predisposition and environmental factors.[7] Environmental factors implicated in the development of gastric cancer include diet, Helicobacter pylori infection, previous gastric surgery, pernicious anemia, adenomatous polyps, chronic atrophic gastritis, and radiation exposure.

Diet

A diet rich in pickled vegetables, salted fish, salt, and smoked meats correlates with an increased incidence of gastric cancer.[7]

A diet that includes fruits and vegetables rich in vitamin C may have a protective effect.[8]

Smoking

Smoking is associated with an increased incidence of stomach cancer in a dose-dependent manner, both for number of cigarettes and for duration of smoking.

Smoking increases the risk of cardiac and noncardiac forms of stomach cancer.[9] Cessation of smoking reduces the risk.

A meta-analysis of 40 studies estimated that the risk was increased by approximately 1.5- to 1.6-fold and was higher in men.[10]

Helicobacter pylori infection

Chronic bacterial infection with H pylori is the strongest risk factor for stomach cancer.

H pylori may infect 50% of the world's population, but many fewer than 5% of infected individuals develop cancer. It may be that only a particular strain of H pylori is strongly associated with malignancy, probably because it is capable of producing the greatest amount of inflammation. In addition, full malignant transformation of affected parts of the stomach may require that the human host have a particular genotype of interleukin (IL) to cause the increased inflammation and an increased suppression of gastric acid secretion. For example, IL-17A and IL-17F are inflammatory cytokines that play a critical role in inflammation. Wu et al found that carriage of IL-17F 7488GA and GG genotypes were associated with an increased risk of gastric cancer.[11]

H pylori infection is associated with chronic atrophic gastritis, and patients with a history of prolonged gastritis have a sixfold increased risk of developing gastric cancer. Interestingly, this association is particularly strong for tumors located in the antrum, body, and fundus of the stomach but does not seem to hold for tumors originating in the cardia.[12]

Previous gastric surgery

Previous surgery is implicated as a risk factor. The rationale is that surgery alters the normal pH of the stomach, which may in turn lead to metaplastic and dysplastic changes in luminal cells.[13]

Retrospective studies demonstrate that a small percentage of patients who undergo gastric polyp removal have evidence of invasive carcinoma within the polyp. This discovery has led some researchers to conclude that polyps might represent premalignant conditions.

Genetic factors

Some 10% of stomach cancer cases are familial in origin.

Genetic factors involved in gastric cancer remain poorly understood, though specific mutations have been identified in a subset of gastric cancer patients. For example, germline truncating mutations of the E-cadherin gene (CDH1) are detected in 50% of diffuse-type gastric cancers, and families that harbor these mutations have an autosomal dominant pattern of inheritance with a very high penetrance.[14]

Other hereditary syndromes with a predisposition for stomach cancer include hereditary nonpolyposis colorectal cancer, Li-Fraumeni syndrome, familial adenomatous polyposis, and Peutz-Jeghers syndrome.

Epstein-Barr virus

The Epstein-Barr virus may be associated with an unusual (< 1%) form of stomach cancer, lymphoepithelioma-like carcinoma.

Pernicious anemia

Pernicious anemia associated with advanced atrophic gastritis and intrinsic factor deficiency is a risk factor for gastric carcinoma.

Gastric ulcers

Gastric cancer may develop in the remaining portion of the stomach following a partial gastrectomy for gastric ulcer.

Benign gastric ulcers may themselves develop into malignancy.

Obesity

Obesity increases the risk of gastric cardia cancer.

Radiation exposure

Survivors of atomic bomb blasts have had an increased rate of stomach cancer. Other populations exposed to radiation may also have an increased rate of stomach cancer.

Bisphosphonates

A large cohort study examined whether use of oral bisphosphonates was associated with an increased risk of esophageal or gastric cancers. No significant difference was observed for increased risk of esophageal or gastric cancers between the bisphosphonate cohort and the control group.[15]

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Contributor Information and Disclosures
Author

Elwyn C Cabebe, MD  Adjunct Clinical Faculty, Department of Internal Medicine, Division of Medical Oncology, Stanford University School of Medicine

Elwyn C Cabebe, MD is a member of the following medical societies: American Association for Cancer Research, American Society of Clinical Oncology, and Philippine Medical Society of Northern California

Disclosure: Nothing to disclose.

Coauthor(s)

Vivek K Mehta, MD  Radiation Oncologist, Director, Center for Advanced Targeted Radiotherapies, Department of Radiation Oncology, Swedish Cancer Institute, Seattle, Washington

Vivek K Mehta, MD is a member of the following medical societies: American Society for Therapeutic Radiology and Oncology, Phi Beta Kappa, and Sigma Xi

Disclosure: Nothing to disclose.

George Fisher Jr, MD  PhD, Associate Professor, Department of Internal Medicine, Division of Medical Oncology, Stanford University School of Medicine

George Fisher Jr, MD is a member of the following medical societies: American Cancer Society and American Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Michael Perry, MD, MS, MACP  Nellie B Smith Chair of Oncology Emeritus, Director, Division of Hematology and Medical Oncology, Deputy Director, Ellis Fischel Cancer Center, University of Missouri-Columbia School of Medicine

Michael Perry, MD, MS, MACP is a member of the following medical societies: Alpha Omega Alpha, American Association for Cancer Research, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Medical Association, American Society of Clinical Oncology, American Society of Hematology, International Association for the Study of Lung Cancer, and Missouri State Medical Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Benjamin Movsas, MD  Vice-Chairman, Department of Radiation Oncology, Fox Chase Cancer Center

Benjamin Movsas, MD is a member of the following medical societies: American College of Radiology, American Radium Society, and American Society for Therapeutic Radiology and Oncology

Disclosure: Nothing to disclose.

Rajalaxmi McKenna, MD, FACP  Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems

Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis

Disclosure: Nothing to disclose.

Chief Editor

Jules E Harris, MD  Clinical Professor of Medicine, Section of Hematology/Oncology, University of Arizona College of Medicine, Arizona Cancer Center

Jules E Harris, MD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Association of Immunologists, American Society of Hematology, and Central Society for Clinical Research

Disclosure: GlobeImmune Salary Consulting

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Stomach and duodenum, coronal section.
 
 
 
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