Etiology of stomach cancer is multifactorial, but Helicobacter pylori plays a significant role. Symptoms include early satiety, obstruction, and bleeding but tend to occur late in the disease. Diagnosis is by endoscopy, followed by CT and endoscopic ultrasonography for staging. Treatment is mainly surgery; chemotherapy may provide a temporary response. Long-term survival is poor except for patients with local disease.

Stomach cancer accounts for an estimated 21,000 cases and about 11,000 deaths in the US annually. Gastric adenocarcinoma accounts for 95% of malignant tumors of the stomach; less common are localized gastric lymphomas (see Lymphomas) and leiomyosarcomas. Stomach cancer is the 2nd most common cancer worldwide, but the incidence varies widely; incidence is extremely high in Japan, China, Chile, and Iceland. In the US, incidence has declined in recent decades to the 7th most common cause of death from cancer. In the US, it is most common among blacks, Hispanics, and American Indians. Its incidence increases with age; > 75% of patients are > 50 yr.

Etiology

Helicobacter pylori infection is the cause of most stomach cancer. Autoimmune atrophic gastritis (see Gastritis and Peptic Ulcer Disease: Autoimmune Metaplastic Atrophic Gastritis) and various genetic factors (see Tumors of the GI Tract: Gastrointestinal Stromal Tumors) are also risk factors. Dietary factors are not proven causes.

Gastric polyps can be precursors of cancer. Inflammatory polyps may develop in patients taking NSAIDs, and fundic foveolar polyps are common among patients taking proton pump inhibitors. Adenomatous polyps, particularly multiple ones, although rare, are the most likely to develop cancer. Cancer is particularly likely if an adenomatous polyp is > 2 cm in diameter or has a villous histology. Because malignant transformation cannot be detected by inspection, all polyps seen at endoscopy should be removed. The incidence of stomach cancer is generally decreased in patients with duodenal ulcer.

Pathophysiology

Gastric adenocarcinomas can be classified by gross appearance:

• Protruding: The tumor is polypoid or fungating.
• Penetrating: The tumor is ulcerated.
• Superficial spreading: The tumor spreads along the mucosa or infiltrates superficially within the wall of the stomach.
• Linitis plastica: The tumor infiltrates the stomach wall with an associated fibrous reaction that causes a rigid “leather bottle” stomach.
• Miscellaneous: The tumor shows characteristics of ≥ 2 of the other types; this classification is the largest.

Prognosis is better with protruding tumors than with spreading tumors because protruding tumors become symptomatic earlier.

Stomach Cancer

Symptoms and Signs

Initial symptoms are nonspecific, often consisting of dyspepsia suggestive of peptic ulcer. Patients and physicians alike tend to dismiss symptoms or treat the patient for acid disease. Later, early satiety (fullness after ingesting a small amount of food) may occur if the cancer obstructs the pyloric region or if the stomach becomes nondistensible secondary to linitis plastica. Dysphagia may result if cancer in the cardiac region of the stomach obstructs the esophageal outlet. Loss of weight or strength, usually resulting from dietary restriction, is common. Massive hematemesis or melena is uncommon, but secondary anemia may follow occult blood loss. Occasionally, the first symptoms are caused by metastasis (eg, jaundice, ascites, fractures).

Physical findings may be unremarkable or limited to heme-positive stools. Late in the course, abnormalities include an epigastric mass; umbilical, left supraclavicular, or left axillary lymph nodes; hepatomegaly; and an ovarian or rectal mass. Pulmonary, CNS, and bone lesions may occur.

Diagnosis

• Endoscopy with biopsy
• Then CT and endoscopic ultrasonography

Differential diagnosis commonly includes peptic ulcer and its complications.

Patients suspected of having stomach cancer should have endoscopy with multiple biopsies and brush cytology. Occasionally, a biopsy limited to the mucosa misses tumor tissue in the submucosa. X-rays, particularly double-contrast barium studies, may show lesions but rarely obviate the need for subsequent endoscopy.

Patients in whom cancer is identified require CT of the chest and abdomen to determine extent of tumor spread. If CT is negative for metastasis, endoscopic ultrasonography should be done to determine the depth of the tumor and regional lymph node involvement. Findings guide therapy and help determine prognosis.

Basic blood tests, including CBC, electrolytes, and liver function tests, should be done to assess anemia, hydration, general condition, and possible liver metastases. Carcinoembryonic antigen (CEA) should be measured before and after surgery.

Screening: Screening with endoscopy is used in high-risk populations (eg, Japanese) but is not recommended in the US. Follow-up screening for recurrence in treated patients consists of endoscopy and CT of the chest, abdomen, and pelvis. If an elevated CEA dropped after surgery, follow-up should include CEA levels; a rise signifies recurrence.

Prognosis

Prognosis depends greatly on stage but overall is poor (5-yr survival: < 5 to 15%) because most patients present with advanced disease. If the tumor is limited to the mucosa or submucosa, 5-yr survival may be as high as 80%. For tumors involving local lymph nodes, survival is 20 to 40%. More widespread disease is almost always fatal within 1 yr. Gastric lymphomas have a better prognosis and are discussed in Lymphomas.

Treatment

• Surgical resection, sometimes combined with chemotherapy, radiation, or both

Treatment decisions depend on tumor staging and the patient's wishes (some may choose to forgo aggressive treatment—see Medicolegal Issues: Advance Directives).

Curative surgery involves removal of most or all of the stomach and adjacent lymph nodes and is reasonable in patients with disease limited to the stomach and perhaps the regional lymph nodes (< 50% of patients). Adjuvant chemotherapy or combined chemotherapy and radiation therapy after surgery may be beneficial if the tumor is resectable.

Resection of locally advanced regional disease results in a 10-mo median survival (vs 3 to 4 mo without resection).

Metastasis or extensive nodal involvement precludes curative surgery, and, at most, palliative procedures should be undertaken. However, the true extent of tumor spread often is not recognized until curative surgery is attempted. Palliative surgery typically consists of a gastroenterostomy to bypass a pyloric obstruction and should be done only if the patient's quality of life can be improved. In patients not undergoing surgery, combination chemotherapy regimens (5-fluorouracilSome Trade Names
ADRUCIL
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, doxorubicinSome Trade Names
ADRIAMYCIN
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, mitomycinSome Trade Names
MUTAMYCIN
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, cisplatinSome Trade Names
PLATINOL
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, or leucovorin in various combinations) may produce temporary response but little improvement in 5-yr survival. Radiation therapy is of limited benefit.

Key Points

• Helicobacter pylori infection is the cause of most stomach cancer.
• Initial symptoms are nonspecific and often resemble those of peptic ulcer disease.
• Screening with endoscopy is used in high-risk populations (eg, Japanese) but is not recommended in the US.
• Overall, survival is poor (5-yr survival: 5 to 15%) because many patients present with advanced disease.
• Curative surgery, perhaps with combined chemotherapy and radiation therapy, is reasonable in patients with disease limited to the stomach and perhaps the regional lymph nodes.

Last full review/revision October 2012 by Elliot M. Livstone, MD

Content last modified November 2012