Stomach cancer
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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 ultrasound for staging. Treatment is mainly surgery; chemotherapy may provide a temporary response. Long-term survival is poor except for those with local disease.
Stomach cancer accounts for about 21,000 cases and 12,000 deaths in the US annually. Gastric adenocarcinoma accounts for 95% of malignant tumors of the stomach; less common are localized gastric lymphomas and leiomyosarcomas. Stomach cancer is the 2nd most common cancer worldwide, but the incidence varies widely; it is extremely high in Japan, 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 in blacks, Hispanics, and American Indians. Its incidence increases with age; > 75% of patients are > 50 yr.
Etiology and Pathophysiology
H. pylori infection is the cause of most stomach cancer. Autoimmune atrophic gastritis and various genetic factors are also risk factors.
Gastric polyps can be precursors of cancer. Inflammatory polyps may develop in patients taking NSAIDs, and fundic foveolar polyps are common in patients taking proton pump inhibitors. Adenomatous polyps, particularly multiple ones, although rare, are the most likely to develop malignancy. Malignancy 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.
Gastric adenocarcinomas can be classified by gross appearance: (1) Protruding—the tumor is polypoid or fungating. (2) Penetrating—the tumor is ulcerated. (3) Superficial spreading—the tumor spreads along the mucosa or infiltrates superficially within the wall of the stomach. (4) Linitis plastica—the tumor infiltrates the stomach wall with an associated fibrous reaction that produces a rigid “leather bottle” stomach. (5) Miscellaneous—the tumor demonstrates characteristics of two or more of the other types; this classification is the largest. Protruding tumors have a better prognosis than spreading tumors because they become symptomatic earlier.
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
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 demonstrate 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 ultrasound should be performed 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 performed to assess anemia, hydration, general condition, and possible liver metastases. Carcinoembryonic antigen (CEA) should be measured before and after surgery.
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 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 Lymphomas.
Treatment
Treatment decisions depend on tumor staging and the patient’s wishes (some may choose to forgo aggressive treatment).
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 is of uncertain benefit.
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 performed only if the patient's quality of life can be improved. In patients not undergoing surgery, combination chemotherapy regimens (5-fluorouracil, doxorubicin, mitomycin, cisplatin, or leucovorin in various combinations) may produce temporary response but little improvement in 5-yr survival. Radiation therapy is of limited benefit.
K. Ozaki, T. Yamagami, K. Nomura and I. Narama
Research Institute of Drug Safety, Setsunan University, Hirakata, Osaka, Japan (KO, IN); and Marupi Lifetech Co., Ltd., Ikeda, Osaka, Japan (TY, KN)
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