Gastric Cancer 

  • Author: Elwyn C Cabebe, MD; Chief Editor: Jules E Harris, MD   more...
 
Updated: Jun 13, 2011
 

Background

Gastric cancer was once the second most common cancer in the world. In most developed countries, however, rates of stomach cancer have declined dramatically over the past half century. In the United States, stomach malignancy is currently the 14th most common cancer.

Decreases in gastric cancer have been attributed in part to widespread use of refrigeration, which has had several beneficial effects: increased consumption of fresh fruits and vegetables; decreased intake of salt, which had been used as a food preservative; and decreased contamination of food by carcinogenic compounds arising from the decay of unrefrigerated meat products. Salt and salted foods may damage the gastric mucosa, leading to inflammation and an associated increase in DNA synthesis and cell proliferation. Other factors likely contributing to the decline in stomach cancer rates include lower rates of chronic Helicobacter pylori infection, thanks to improved sanitation and use of antibiotics, and increased screening in some countries.[1]

Nevertheless, gastric cancer is still the second most common cause of cancer-related death in the world, and it remains difficult to cure in Western countries, primarily because most patients present with advanced disease. Even patients who present in the most favorable condition and who undergo curative surgical resection often die of recurrent disease. However, 2 studies have demonstrated improved survival with adjuvant therapy: a US study using postoperative chemoradiation[2] and a European study using preoperative and postoperative chemotherapy.[3]

Anatomic aspects

The molecular biology responsible for carcinogenesis, tumor biology, and response to therapy in stomach cancer are active areas of investigation but are not addressed in this review. Instead, this article focuses on clinical management, which first requires a thorough understanding of gastric anatomy.

An image depicting stomach anatomy can be seen below.

Stomach and duodenum, coronal section. Stomach and duodenum, coronal section.

The stomach begins at the gastroesophageal junction and ends at the duodenum. The stomach has 3 parts: the uppermost part is the cardia; the middle and largest part is the body, or fundus; and the distal portion, the pylorus, connects to the duodenum. These anatomic zones have distinct histologic features. The cardia contains predominantly mucin-secreting cells. The fundus contains mucoid cells, chief cells, and parietal cells. The pylorus is composed of mucus-producing cells and endocrine cells.

The stomach wall is made up of 5 layers. From the lumen out, the layers include the mucosa, the submucosa, the muscularis layer, the subserosal layer, and the serosal layer. The peritoneum of the greater sac covers the anterior surface of the stomach. A portion of the lesser sac drapes posteriorly over the stomach. The gastroesophageal junction has limited or no serosal covering. The right portion of the anterior gastric surface is adjacent to the left lobe of the liver and the anterior abdominal wall. The left portion of the stomach is adjacent to the spleen, the left adrenal gland, the superior portion of the left kidney, the ventral portion of the pancreas, and the transverse colon.

The site of stomach cancer is classified on the basis of its relationship to the long axis of the stomach. Approximately 40% of cancers develop in the lower part, 40% in the middle part, and 15% in the upper part; 10% involve more than one part of the organ. Most of the decrease in gastric cancer incidence and mortality in the United States has involved cancer in the lower part of the stomach; the incidence of adenocarcinoma in the cardia has actually shown a gradual increase.

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Pathophysiology

Ooi et al identified 3 oncogenic pathways that are deregulated in the majority (>70%) of gastric cancers: the proliferation/stem cell, NF-kappa β, and Wnt/beta-catenin pathways. Their study suggests that interactions between these pathways may play an important role in influencing disease behavior and patient survival.[4]

Understanding the vascular supply of the stomach allows understanding of the routes of hematogenous spread. The vascular supply of the stomach is derived from the celiac artery. The left gastric artery, a branch of the celiac artery, supplies the upper right portion of the stomach. The common hepatic artery branches into the right gastric artery, which supplies the lower portion of the stomach, and the right gastroepiploic branch, which supplies the lower portion of the greater curvature.

Understanding the lymphatic drainage can clarify the areas at risk for nodal involvement by cancer. The lymphatic drainage of the stomach is complex. Primary lymphatic drainage is along the celiac axis. Minor drainage occurs along the splenic hilum, suprapancreatic nodal groups, porta hepatis, and gastroduodenal areas.

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Epidemiology

Frequency

United States

The American Cancer Society estimates that 21,130 cases of gastric cancer will be diagnosed in 2009 (12,820 in men, 8,310 in women) and that 10,620 persons will die of the disease.[5] Gastric cancer is the seventh leading cause of cancer deaths.

International

Once the second most common cancer worldwide, stomach cancer has dropped to fourth place, after cancers of the lung, breast, and colon and rectum. However, stomach cancer remains the second most common cause of death from cancer. The American Cancer Society estimates that in 2007 there were an estimated one million new cases, nearly 70% of them in developing countries, and about 800,000 deaths.[1]

Tremendous geographic variation exists in the incidence of this disease around the world. Rates of the disease are highest in Asia and parts of South America and lowest in North America.[1] The highest death rates are recorded in Chile, Japan, South America, and the former Soviet Union.

Mortality/Morbidity

The 5-year survival rate for curative surgical resection ranges from 30-50% for patients with stage II disease and from 10-25% for patients with stage III disease. Because these patients have a high likelihood of local and systemic relapse, some physicians offer them adjuvant therapy. The operative mortality rate for patients undergoing curative surgical resection at major academic centers is less than 3%.

A review of 8 trials by Rothwell et al found allocation to aspirin reduced death caused by cancer. Individual patient data were available from 7 of the 8 trials. Benefit was apparent after 5 years of follow-up. The 20-year risk of cancer death was also lower in the aspirin group for all solid cancers. A latent period of 5 years was observed before risk of death was decreased for esophageal, pancreatic, brain, and lung cancers. A more delayed latent period was observed for stomach, colorectal, and prostate cancer. Benefit was only seen for adenocarcinomas in lung and esophageal cancers. The overall effect on 20-year risk of cancer death was greatest for adenocarcinomas.[6]

Race

The rates of gastric cancer are higher in Asian and South American countries than in the United States. Japan, Chile, and Venezuela have developed a very rigorous early screening program that detects patients with early stage disease (ie, low tumor burden). These patients appear to do quite well. In fact, in many Asian studies, patients with resected stage II and III disease tend to have better outcomes than similarly staged patients treated in Western countries. Some researchers suggest that this reflects a fundamental biologic difference in the disease as it manifests in Western countries.

In the United States, Asian and Pacific Islander males and females have the highest incidence of stomach cancer, followed by black, Hispanic, white, American Indian, and Inuit populations.

Sex

In the United States, gastric cancer affects slightly more men than women; the American Cancer Society estimates that in 2009, 12,820 new cases will occur in men and 8,310 in women.[5] Worldwide, however, gastric cancer rates are about twice as high in men as in women.[1]

Age

Most patients are elderly at diagnosis. The median age for gastric cancer in the United States is 70 years for males and 74 years for females. The gastric cancers that occur in younger patients may represent a more aggressive variant or may suggest a genetic predisposition to development of the disease.

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

George Fisher, MD, PhD 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, Professor, Department of Internal Medicine, Division of Hematology and Oncology, 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, Division of Hematology/Medical Oncology, Department of Internal Medicine, University of Arizona College of Medicine; Consulting Staff, 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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