Stomach cancer overview
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Parminder Dhingra, M.D. [2] Mohammed Abdelwahed M.D[3]
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Overview
Stomach cancer (also called gastric cancer) can develop in any part of the stomach and may spread throughout the stomach and to other organs; particularly the esophagus and the small intestine. Stomach cancer causes nearly one million deaths worldwide per year.
Historical perspective
John Jones was the first to perform a gastric resection in animals. In 1881, Billroth’s first human operation has been done. In 1897, Schlatter has done the first esophago-enterostomy after gastrectomy. Between 1884 to 1929, Finney’s and Rienhoff were the first to perform partial gastrectomy showing less side effects and less mortality rates.
Classification
Stomach cancer may be classified into adenocarcinoma, lymphoma, gastrointestinal stromal tumor, and carcinoid tumor. Gastric cancer classifications are Padova classification that classified gastric cancer into five types according tot degree of dysplasia. Japanese classification subdivided gastric cancer according to the atypia degree to five types also.
Pathophysiology
There are many molecular causes of gastric cancer; H. pylori and gastric cancer has a strong correlation. This is related to nitric oxides accumulation produced by inflammatory cells responding to H. pylori infection. The pathophysiology of stomach cancer depends on histologic subtypes. K-ras mutations is found in invasive cancers and intestinal metaplasia. Inactivation of p53 in gastric epithelial cells reduce their ability to undergo apoptosis. DNA methylation of gene promoters can silence the expression of CDH1. Beta-catenin mutation is a frequent cause of Wnt pathway activation in gastric cancer. Diffuse gastric carcinomas do not have a precancerous lesion. They are highly metastatic with a poorer prognosis than intestinal cancers. When the entire stomach wall is infiltrated, it results in a rigid thickened stomach wall called linitis plastica. There are many associated diseases t gastric cancer; Hereditary diffuse gastric cancer, Gastric Adenocarcinoma and Proximal Polyposis of the Stomach, Lynch syndrome, Familial adenomatous polyposis, Li-Fraumeni syndrome, Peutz Jeghers syndrome, Juvenile polyposis, Hereditary breast and ovarian cancer syndrome, Cowden's syndrome. There are five gross pathology types of gastric cancer; superficial, ulcerative, infiltrative ulcerative, diffuse infiltrative, and unclassified. There are two major histological classifications for gastric cancer; Japanese classification and WHO classification. Generally, the main two types are; Intestinal type adenocarcinoma and diffuse type adenocarcinoma.
Differential diagnosis
Stomach cancer must be differentiated from gastric lymphoma, gastric metastasis, gastritis, benign gastric ulcer, menetrier disease.
Epidemiology and Demographics
Stomach cancer is the fifth most common cancer worldwide. In the United States, stomach cancer represents roughly 1.3% of all new cancer cases yearly. In 2011, the age-adjusted prevalence of stomach cancer was estimated to be 23.5 cases per 100,000 individuals in the United States. Stomach cancer is two times more common in men than in women, and the incidence increases with age. Incidence of gastric cancer under 65 years is 2.9 per 100,000.
Risk Factors
Risk factors vary according to the type of gastric cancer. Common risk factors for intestinal-type of stomach cancer are chronic superficial gastritis caused by; Helicobacter pylori infection, pernicious anemia, a high salt diet, chronic inflammation results in epithelial cell damage. Risk factors for diffuse-type gastric cancer are salt and salt-preserved foods, nitroso compounds, fruits and fibers, obesity, smoking, Helicobacter pylori, nonsteroidal antinflammatory, Ebstien-Barr virus, gastric surgery, irradiation, and familial predisposition.
Screening
The two main modalities for gastric cancer screening are upper endoscopy and contrast radiography. In countries with a high incidence, of gastric cancer such as east Asia countries, universal screening is recommended. In areas of low gastric cancer incidence, screening for gastric cancer with upper endoscopy should be reserved for specific high-risk subgroups. The sensitivity rates for upper endoscopy were 69 % and upper GI series were 37%. Both studies had a specificity of 96%.
Natural history, Complications and Prognosis
If left untreated, the five-year survival rates of gastric cancer range from almost no survival for patients with disseminated disease to almost 50% survival for patients with localized distal gastric cancers confined to resectable regional disease. Higher recurrence rates are seen with those who have piecemeal or incomplete resections. Depending on the extent of the tumor at the time of diagnosis, the prognosis may vary. However, the prognosis is generally regarded as poor. Complications of gastric cancer are ascites, gastrointestinal bleeding, distant metastasis to other organs, weight loss, recurrence, and treatment complications. The prognosis of patients with gastric cancer is related to tumor extent that includes direct tumor extension and lymph nodes involvement. The five-year survival rate for treated early gastric cancer is over 90 percent: nearly 100 percent for mucosal tumors, and 80 to 90 percent for submucosal tumors.
Staging
According to the American Joint Committee on Cancer, there are 4 stages of stomach cancer based on the tumor spread.
Symptoms
Symptoms of stomach cancer include abdominal pain, bloating, weight loss, hematemesis, melena, and dysphagia. Twenty-five percent of patients have a history of gastric ulcer.
Physical Examination
Patients with stomach cancer generally appear healthy. Common physical examination findings include abdominal distention, palpation of an abdominal mass, and pallor. Leser-Trelat sign and presence of Virchow's node (left supraclavicular lymphadenopathy), Sister Mary Joseph nodule (visible periumbilical nodule), Blumer's shelf (rectal mass/shelf on rectal exam) and/or Trousseau's syndrome (migratory phlebitis) on physical examination are highly suggestive of stomach cancer.
Endoscopy and Biopsy
Endoscopic ultrasonography (EUS) is the most reliable diagnostic technique for evaluating the depth of invasion of primary gastric cancers. Endoscopic ultrasonography is not the procedure of choice for detecting lymph nodes.
CT
Abdominal CT scan may be helpful in the diagnosis of stomach cancer. It is used to evaluate metastatic disease, especially hepatic or adnexal metastases, ascites, or distant nodal spread. Integrated PET/CT imaging can be useful to confirm malignant involvement of CT-detected lymphadenopathy. A negative PET CT is not helpful since even large tumors with a diameter of several centimeters can be falsely negative if the tumor cells have a fairly low metabolic activity.
Other imaging findings
Barium studies may be diagnostic of stomach cancer. The sensitivity of barium meals maybe 14%. False-negative barium studies can occur in 50 percent of cases. There are three types of results in early gastric cancer: polypoid, ulcerated, and superficial.
Other diagnostic studies
Laparoscopy has the advantage of directly visualizing the liver surface, the peritoneum, and local lymph nodes. Diagnostic laparoscopy is especially important for patients who are being considered for neoadjuvant therapy trials.
Medical therapy
The optimal therapy for stomach cancer depends on the stage at diagnosis. It is indicated for; patients with unresectable or recurrent disease, after non-curative R2 resection, patients with unresectable T4b disease, extensive nodal disease, Hepatic metastases, Peritoneal dissemination or other M1 disease. Response to the treatment should be evaluated by examinations that may include CT, endoscopy and contrast radiography. Adjuvant therapy includes one cycle of fluorouracil (425 mg/m2) + leucovorin calcium (20 mg/m2) for five days followed by radiation therapy for one month given with the same chemotherapy regimen on days 1 through 4 and the last three days of the month. For patients with potentially resectable disease not yet resected, neoadjuvant therapy is preferred over initial surgery. Another benefit of neoadjuvant chemotherapy is that patients who are at high risk of developing distant metastases may be spared the morbidity of unnecessary gastrectomy if evidence of distant metastases emerges after chemotherapy. Preoperative combined chemotherapy and radiation therapy is more commonly used for esophageal, esophagogastric junction, and gastric cardia cancers than for potentially resectable adenocarcinomas. For locally advanced unresectable and metastatic tumors, goals of chemotherapy include palliation of symptoms, improvement in the quality of life, and prolongation of survival. Patients with the presence of human epidermal growth factor receptor 2 (HER2) overexpression are potential candidates for trastuzumab.
Surgery
Surgery is the mainstay of treatment for stomach cancer. Endoscopic resection is suggested for early gastric cancer. There are criteria for endoscopic resection of early gastric cancer. Methods for endoscopic resection include endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). Side effects of endoscopy includes bleeding and perforation. For T1 tumors, a gross resection margin of 2 cm should be obtained. Proximal margin of at least 3 cm is recommended for T2 or deeper tumors with an expansive growth pattern and 5 cm for those with an infiltrative growth pattern. For tumors invading the esophagus, a 5-cm margin is not necessarily required, but frozen section examination of the resection line is desirable to ensure aR0 resection. There is a debate about optimal lymph nodes removal. D1 lymphadenectomy refers to a dissection of only the perigastric lymph nodes. D2 lymphadenectomy is an extended lymph node dissection, includes removal of nodes along the hepatic, left gastric, celiac, and splenic arteries, as well as those in the splenic hilum. D3 dissection is a super extended lymphadenectomy. The surgery includes D2 lymphadenectomy plus the removal of nodes within the porta hepatis and periaortic regions.
Primary prevention
Effective measures for the primary prevention of stomach cancer include smoking cessation, helicobacter pylori infection eradication, and having a balanced diet rich in fruits and vegetables. In areas of low gastric cancer incidence, screening for gastric cancer with upper endoscopy should be reserved for specific high-risk subgroups. Individuals at increased risk for gastric cancer include; gastric adenomas, pernicious anemia, gastric intestinal metaplasia, familial adenomatous polyposis, Lynch syndrome, Peutz-Jeghers syndrome, Juvenile polyposis syndrome.
Secondary prevention
Gastric cancer secondary prevention is indicated for all patients after gastric surgeries. Physical examination, complete blood count, imaging or endoscopy are indicated to decrease levels of recurrence.