Stomach Cancer

Risk factors for stomach cancer include the following:

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 Risk factor references 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... read more ).

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 Risk factor references 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... read more ). 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 Risk factor references 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... read more ). Breast cancer surveillance with annual breast MRI beginning at age 30 is also recommended for women with the CDH1 mutation (4 Risk factor references 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... read more ). 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 Risk factor references 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... read more ). Other genetic syndromes that predispose to stomach cancer include familial adenomatous polyposis Familial Adenomatous Polyposis Familial adenomatous polyposis is a hereditary disorder causing numerous colonic polyps and frequently results in colon carcinoma, often by age 40. Patients are usually asymptomatic but may... read more , Lynch syndrome Lynch Syndrome Lynch syndrome is an autosomal dominant disorder responsible for 2 to 3% of cases of colorectal cancer ( 1). Symptoms, initial diagnosis, and treatment are similar to other forms of colorectal... read more , juvenile polyposis syndrome, and Peutz-Jeghers syndrome Peutz-Jeghers Syndrome Peutz-Jeghers syndrome is an autosomal dominant disease with multiple hamartomatous polyps in the stomach, small bowel, and colon along with distinctive pigmented skin lesions. Most (66 to 94%)... read more .

Gastric adenocarcinomas can be classified by gross appearance:

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

Initial symptoms of stomach cancer are nonspecific, often consisting of dyspepsia Dyspepsia Dyspepsia is a sensation of pain or discomfort in the upper abdomen; it often is recurrent. It may be described as indigestion, gassiness, early satiety, postprandial fullness, gnawing, or burning... read more suggestive of peptic ulcer Peptic Ulcer Disease A peptic ulcer is an erosion in a segment of the gastrointestinal mucosa, typically in the stomach (gastric ulcer) or the first few centimeters of the duodenum (duodenal ulcer), that penetrates... read more . 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 Dysphagia Dysphagia is difficulty swallowing. The condition results from impeded transport of liquids, solids, or both from the pharynx to the stomach. Dysphagia should not be confused with globus sensation... read more 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.

Differential diagnosis of stomach cancer commonly includes peptic ulcer and its complications Complications A peptic ulcer is an erosion in a segment of the gastrointestinal mucosa, typically in the stomach (gastric ulcer) or the first few centimeters of the duodenum (duodenal ulcer), that penetrates... read more .

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.

Stomach cancer treatment decisions depend on tumor staging and the patient’s wishes (some may choose to forgo aggressive treatment—see Advance Directives Advance Directives Advance directives are legal documents that extend a person's control over health care decisions in the event that the person becomes incapacitated. They are called advance directives because... read more ).

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 (1 Treatment references 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... read more ) but has been refined to the current standard of care termed perioperative FLOT (5-fluorouracil, leucovorin, oxaliplatin, docetaxel) (2 Treatment references 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... read more ).

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

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, various combination chemotherapy regimens (5-fluorouracil, capecitabine, doxorubicin, mitomycin, cisplatin, oxaliplatin, irinotecan, paclitaxel, docetaxel, or leucovorin) may produce a temporary response and only a minor improvement in survival.

In recent years, targeted therapies using trastuzumab for tumors that overexpress human epidermal growth factor receptor 2 (HER2+) tumors and ramucirumab (a vascular endothelial growth factor [VEGF] inhibitor) in conjunction with chemotherapy have been used in advanced cancer. Immunotherapy such as with pembrolizumab is available for use in patients with programmed cell death ligand 1 (PD-L1)–positive advanced or metastatic gastric cancer. Programmed cell death receptor 1 inhibitors (eg, nivolumab) are available for use outside the United States for patients with advanced gastric cancer. Radiation therapy is of limited benefit for patients with metastases.

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 Prognosis references 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... read more , 2 Prognosis references 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... read more ). If the tumor is limited to the mucosa or submucosa, 5-year survival may be as high as 90% (3 Prognosis references 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... read more ). 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 Hodgkin Lymphoma Hodgkin lymphoma is a localized or disseminated malignant proliferation of cells of the lymphoreticular system, primarily involving lymph node tissue, spleen, liver, and bone marrow. Symptoms... read more and Non-Hodgkin Lymphomas Non-Hodgkin Lymphomas Non-Hodgkin lymphomas are a heterogeneous group of disorders involving malignant monoclonal proliferation of lymphoid cells in lymphoreticular sites, including lymph nodes, bone marrow, the... read more ).