Stomach Cancer

Risk factors for stomach cancer include the following:

• Helicobacter pylori infection (when it is associated with extensive gastric intestinal metaplasia)

• Autoimmune atrophic gastritis

• Smoking (and people who smoke may have an impaired response to treatment)

• Gastric polyps

• Genetic factors

Dietary factors are not proven causes; however, the World Health Organization (WHO) International Agency for Research on Cancer (IARC) has reported a positive association between consumption of processed meat and stomach cancer (1).

Gastric polyps can be precursors of cancer. Inflammatory polyps may develop in patients taking nonsteroidal anti-inflammatory drug (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.

Various genetic factors are also risk factors. Hereditary diffuse gastric cancer is associated with a mutation in the cadherin 1 gene (CDH1) and has no precursor lesion. This mutation is an autosomal dominant trait with high penetrance. Affected patients usually develop gastric cancer at an early age (average age 38) and have about an 80% lifetime risk of developing gastric cancer (2). Affected women are also at high risk of developing lobular breast cancer. Patients with personal or family history of diffuse gastric cancer and/or lobular breast cancer in multiple family members, especially if they were diagnosed before age 50, should be referred for genetic counseling and testing. Prophylactic gastrectomy should be offered to asymptomatic carriers of the CDH1 mutation between the ages of 18 and 40 (3). Breast cancer surveillance with annual breast MRI beginning at age 30 is also recommended for women with the CDH1 mutation (4). There are case reports of colorectal cancer in CDH1 mutation carriers. Data are insufficient to recommend colon cancer screening of all carriers or their families; however, if colon cancer has been diagnosed in a carrier, their family members should have colon cancer screening beginning at age 40 or at an age 10 years younger than when the youngest family member was diagnosed (4). Other genetic syndromes that predispose to stomach cancer include familial adenomatous polyposis, Lynch syndrome, juvenile polyposis syndrome, and Peutz-Jeghers syndrome.

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

Image

Image provided by David M. Martin, MD.

Initial symptoms of stomach cancer 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, central nervous system, and bone lesions may occur.

• Endoscopy with biopsy

• Then CT and endoscopic ultrasonography

Differential diagnosis of stomach cancer 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 complete blood count, electrolytes, and liver tests, should be done to assess anemia, hydration, general condition, and possible liver metastases. The carcinoembryonic antigen (CEA) level should be measured before and after surgery.

• Surgical resection, sometimes combined with chemotherapy, radiation, or both (chemoradiation)

Stomach cancer treatment decisions depend on tumor staging and the patient’s wishes (some may choose to forgo aggressive treatment—see Advance Directives).

Curative surgery involves removal of most (subtotal gastrectomy) or all (total gastrectomy) 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). Depending on the initial stage of the tumor, some patients receive chemotherapy before surgery and after surgery. This strategy, termed perioperative chemotherapy, was the standard of care (12).

For patients with inadequate lymphadenectomy or with node-positive or incompletely resected disease, adjuvant chemotherapy or chemoradiation is sometimes used.

Prognosis depends greatly on stage but overall is poor (5-year survival: < 5 to 15%) because most patients present with advanced disease. Median overall survival in well-selected patients after perioperative chemotherapy and surgery can be as high as 50 months based on modern randomized trials (1, 2). If the tumor is limited to the mucosa or submucosa, 5-year survival may be as high as 90% (3). For tumors involving local lymph nodes, survival is correlated with the number of involved nodes. More widespread disease is almost always fatal within 6 to 12 months.

Gastric lymphomas have a better prognosis (see Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma and Non-Hodgkin Lymphomas).