Signs and Symptoms
Most gastric cancers in Western societies are diagnosed at an advanced stage. Presenting signs and symptoms are often nonspecific and typically include pain, weight loss, vomiting, and anorexia.
Hematemesis is present in 10% to 15% of patients.
Peritoneal implants to the pelvis may be palpable on rectal examination (Blumer's shelf). Extension of disease to the liver may be appreciated as hepatomegaly on physical examination. Nodal metastases can be found in the supraclavicular fossa (Virchow's node), axilla, or umbilical region. Ascites can accompany advanced intraperitoneal spread of disease.
Routine screening for gastric cancer is generally not performed in Western countries because the disease is so uncommon. However, screening appears more effective in high-incidence areas. Mass screening, as has been practiced in Japan since the 1960s, has probably contributed to the 2.5-fold improvement in long-term survival compared with Western countries, though differences in surgical technique and biology may also play a role.
Endoscopy and Barium X-rays
The diagnosis of gastric cancer in a patient presenting with any constellation of the symptoms previously described revolves around the use of upper endoscopy or double-contrast barium X-rays. The advantage of endoscopy is that it allows for direct visualization of abnormalities and directed biopsies. Barium X-rays do not facilitate biopsies but are less invasive and may provide information regarding motility.
Once a diagnosis has been established and careful physical examination and routine blood tests have been performed, a CT scan of the chest, abdomen, and pelvis should be obtained to help assess tumor extent, nodal involvement, and metastatic disease. CT may demonstrate an intraluminal mass arising from the gastric wall or focal or diffuse gastric wall thickening. It is not useful in determining the depth of tumor penetration unless the carcinoma has extended through the entire gastric wall. Direct extension of the gastric tumor to the liver, spleen, or pancreas can be visualized on CT, as can metastatic involvement of celiac, retrocrural, retroperitoneal, and porta hepatis nodes. Ascites, intraperitoneal seeding, and distant metastases (liver, lungs, bone) can also be detected.
Endoscopic ultrasonography (EUS) is a staging technique that complements information gained by CT. Specifically, depth of tumor invasion, including invasion of nearby organs, can be assessed more accurately by EUS than by CT, and EUS is particularly accurate in differentiating early T-stage from late T-stage disease. Furthermore, perigastric regional nodes (including the celiac access) are more accurately evaluated by EUS, whereas regional nodes farther from the primary tumor are more accurately evaluated by CT. Specific ultrasonographic features may aid in the diagnosis and staging of patients with gastric lymphomas.
Laparoscopy is particularly suited to detect small-volume visceral and peritoneal metastases missed on a CT scan. It should be performed prior to curative-intent locoregional therapy or preoperative chemoradiation therapy.
A bone scan should be obtained if the patient has bony pain or an elevated alkaline phosphatase level.
Positron emission tomographic (PET) scanning may be used to show distant metastatic disease and may also be helpful in assessing response to neoadjuvant therapy. In the latter setting, PET response correlates with better survival. As many as 40% of gastric cancers may not be detected by PET, and this modality may not be optimal for staging tumors of mucinous histology. It does not have an established role in routine preoperative imaging of potentially resectable patients, but may be of use when combined with CT imaging.
Adenocarcinoma is the predominant form of gastric cancer, accounting for approximately 95% of cases. Histologically, adenocarcinomas are classified as intestinal or diffuse; mixed types occur but are rare. Intestinal-type cancers are characterized by cohesive cells that form glandlike structures and are often preceded by intestinal metaplasia. Diffuse-type cancers are composed of infiltrating gastric mucous cells that infrequently form masses or ulcers.
Primary lymphoma of the stomach is increasing in frequency and, occasionally, may be difficult to distinguish from adenocarcinoma.
GI stromal tumors (GISTs) are mesenchymal tumors of the GI tract, most commonly arising from the stomach. These tumors share an ancestor with, or arise from, the interstitial cells of Cajal (the pacemaker cells of the gut). GISTs commonly express KIT (CD117), but this is not required for diagnosis. Most GISTs have mutations in either the KIT or PDGFR (platelet-derived growth factor receptor) genes.
Other Histologic Types
Infrequently, other histologic types are found in the stomach, such as squamous cell carcinomas, small-cell carcinomas, and carcinoid tumors.
Metastatic spread of disease from primaries in other organs (eg, breast cancer and melanoma) is also seen occasionally.
Gastric carcinomas spread by direct extension (lesser and greater omentum, liver and diaphragm, spleen, pancreas, transverse colon); regional and distant nodal metastases; hematogenous metastases (liver, lungs, bone, brain); and peritoneal metastases. Multicentricity characterizes up to 20% of gastric cancers. In younger women, the ovaries are at risk (Krukenberg tumors).
At present, epithelial gastric cancers are most commonly staged by the tumor-node-metastasis staging system (TNM) system (Table 1). Lymphomas, carcinoids, and sarcomas are not covered by these TNM criteria. The most recent update of the TNM does include a system encompassing GISTs, but this system is not yet widely used.
A more detailed Japanese staging system has been shown to have prognostic importance in gastric cancer. However, these results have not yet been duplicated in the United States, and this system is not widely used around the world. Resected GISTs can be assigned a numeric risk of recurrence based on tumor size, mitotic rate, and location of the primary.
Aneuploidy may predict a poor prognosis in patients with adenocarcinoma of the distal stomach. High plasma levels of vascular endothelial growth factor (VEGF) and the presence of carcinoembryonic antigen (CEA) in peritoneal washings predict poor survival in surgically resected patients. As with colorectal cancer, intratumoral levels of dihydropyrimidine dehydrogenase (DPD) may be prognostic of gastric cancer; low levels appear to predict better response to fluorouracil(Drug information on fluorouracil) (5-FU)-based chemotherapy and longer survival. The prognostic implications of tumor-suppressor genes and oncogenes are an area of active investigation. Patients with cancers of the diffuse type fare worse than those with intestinal-type lesions.
It has long been known that survival rates for patients with gastric cancers are higher in Asian nations than in the United States, but it was not clear whether this represents results of superior surgical techniques or racial differences in underlying biology. Recent analysis of outcomes in Asian Americans vs white patients suggests that true differences exist in tumor biology, though the specifics have not yet been identified.