Gastric Adenocarcinoma

Epidemiology

In 2016, the American Cancer Society estimated that in the United States 26,370 people will be diagnosed with gastric cancer with 10,730 deaths. Worldwide, however, gastric cancer remains the fifth most common cancer and a leading cause of cancer mortality. The incidence of gastric cancer has considerable geographic variability with a significantly higher occurrence in Asia and Latin America than in North America and Europe.

The average age of diagnosis in the United States is 69 years of age with the majority of patients diagnosed in the seventh decade of life and later. Men are more likely to have gastric cancer than women, and Hispanic Americans, African Americans, and Asian/Pacific Islanders are more frequently affected than non-Hispanic whites. Individuals with lower socioeconomic status are more likely to be affected in both the United States and in developing countries.

Since 1930, the incidence of gastric cancer has decreased significantly, although the reasons for this change are unclear. The incidence of tumors located distally within the stomach have decreased, whereas the incidence of more proximal gastric tumors has increased. Despite the decreasing incidence, gastric cancer remains highly lethal in the United States with an anticipated overall 5-year survival rate of 29%.

Risk Factors

Known risk factors for gastric adenocarcinoma include Helicobacter pylori infection, a history of mucosa-associated lymphoid tissue (MALT) lymphoma, the presence of adenomatous gastric polyps, previous gastric operations, pernicious anemia, atrophic gastritis, intestinal metaplasia, exposure to nitrosamines from cured or smoked foods, tobacco use, and family history. A relationship between obesity and gastric cancer has not been identified definitively, although a hypothesis exists that increasing rates of gastroesophageal reflux disease (GERD) associated with obesity may predispose individuals to more proximal tumors. In addition, lower rates of gastric cancer are observed in individuals with a diet high in fresh fruits and vegetables.

Certain ethnicities are at risk for the development of gastric adenocarcinoma. Japanese, Koreans, Vietnamese, Native Americans, and people of Pacific Island descent are at the greatest risk. In contrast, Filipinos and Caucasians are at the lowest risk, and Chinese, Latinos, and people of African descent are at intermediate risk.

Familial syndromes such as Peutz-Jeghers and familial adenomatous polyposis (FAP) harbor an increased risk of gastric cancer. Mutations in proteins such as E-cadherin, p53, and BRCA2 have also been shown to increase the potential for the development of gastric adenocarcinoma. A complete list of risk factors is presented in Table 61.1 .

Pathology

Ninety to 95% of gastric cancers are adenocarcinoma with the remainder being attributed to lymphoma, gastrointestinal stromal tumors, and carcinoid tumors. Although several histopathology classification systems exist, the most frequently used is the Lauren classification. This classifies gastric adenocarcinomas as intestinal (well differentiated) and diffuse (poorly differentiated).

Intestinal-type adenocarcinomas are derived from the gastric mucosa and form glands. They are more frequently associated with hematogenous metastases and are observed in elderly patients, men, or those individuals in high-risk populations. They are also more common in the distal portion of the stomach. This type of adenocarcinoma is associated with the risk factors of H. pylori infection, chronic atrophic gastritis, intestinal metaplasia, and diets high in nitrosamines.

Diffuse-type adenocarcinoma arises from the lamina propria and spreads through the submucosa. Lymphatic metastases are more common with diffuse-type cancers, which are more predominant in younger patients and women. In contrast to intestinal type, diffuse-type adenocarcinomas are not gland-forming and are more frequently observed in the proximal stomach. In addition, diffuse-type cancers may have transmural extension, develop peritoneal metastases, and are more aggressive overall. Linitis plastica , involvement of the entire stomach, is a rare and aggressive form of diffuse-type cancer that constitutes less than 10% of all gastric adenocarcinomas.

Diagnosis

The early signs and symptoms of gastric cancer are nonspecific and include nausea and epigastric pain. As a result, the majority of cancers are diagnosed at advanced stages. Physical exam findings are also nonspecific, but may include palpable lymph nodes such as the Sister Mary Joseph node in the periumbilical region, the Virchow node in the left supraclavicular region, or the Blumer shelf, which is a palpable prerectal drop metastases that may be evident on digital rectal exam. Development of a palpable abdominal mass or ascites are findings of advanced disease.

As with all suspected malignancies, a complete history and physical examination are essential. Laboratory values including a complete blood count and chemistry and nutritional parameters should be obtained. Many tumor markers may be elevated in the setting of gastric cancer, including carcinoembryonic antigen (CEA), CA-125, CA 19-9, and β-HCG. These biomarkers, however, lack sufficient sensitivity and specificity to establish a diagnosis. Imaging with computed tomography (CT) of the chest, abdomen, and pelvis with oral and intravenous contrast should be obtained, but the diagnosis is established definitively with an upper endoscopy and biopsy confirmation of an adenocarcinoma. Endoscopic ultrasound (EUS) accurately assesses the depth of tumor invasion and enlargement of perigastric lymph nodes, although this technology may not be available in all facilities.

Cross-sectional imaging with CT scan or magnetic resonance imaging (MRI) is useful for the evaluation of metastatic disease. Positron emission tomography (PET) may also be used, as most gastric cancers are PET avid. Both MRI and PET scans, however, may be cost-prohibitive, not universally available, and unnecessary in the presence of a high-quality CT. If metastatic disease is identified, human epidermal growth factor receptor 2 (HER2-neu) testing is recommended. In addition, screening for family history and smoking cessation are important points of assessment during the initial diagnosis.

Diagnostic laparoscopy and peritoneal washings may be useful in identifying small-volume metastatic disease that is not obvious with other diagnostic modalities. In recent studies, it was reported that 30% of patients were upstaged after diagnostic laparoscopy, thereby changing the overall management. National Comprehensive Cancer Network (NCCN) recommendations include the use of diagnostic laparoscopy and peritoneal washings for cytology for all tumors stage IB or higher when resection is considered.

Gastric cancers and esophageal cancers are managed differently with respect to neoadjuvant, adjuvant, and surgical therapy. Esophagogastric junction (EGJ) tumors are assessed using the Siewert classification, which for gastric adenocarcinoma includes only the Siewert type III lesions. These tumors are defined as subcardial carcinomas with the tumor epicenter located 2 to 5 cm below the EGJ with infiltration of the EGJ and esophagus from below. Siewert type I and II lesions are considered esophageal cancers and their management is beyond the scope of this chapter.

Endoscopic screening programs in endemic areas are recommended and have been shown to diagnose tumors at an earlier stage. This practice is not applicable to areas where the incidence of gastric cancer is low, and thus, screening is not currently recommended in the United States.

Staging

The American Joint Committee on Cancer (AJCC) TNM system is the most widely used staging system for gastric cancer. The system assesses the primary tumor (T), the presence of lymph node involvement (N), and the presence of metastatic disease (M). T stage is based on the depth of invasion of the tumor. N stage identifies lymph node involvement and requires assessment of at least 15 lymph nodes. Metastatic disease is identified as distant metastasis including positive cytology from peritoneal washings. Complete descriptions of all TNM levels and stages are presented in Tables 61.2 and 61.3 .