Gastric Cancer

PATIENT HISTORY

A 72-year-old Japanese immigrant was brought in by his family with complaints of difficulty in eating, vague abdominal pain, and weight loss. Endoscopy and biopsy confirmed gastric adenocarcinoma (Figure1). Liver metastases were found on abdominal CT. The family and the patient chose only comfort measures and the patient died 6 months later.

Figure 1. Endoscopy show a raise and irregular
mass in the antrum of the stomach deforming the pylorus

INTRODUCTION

Gastric cancer is a malignant neoplasm of the stomach, usually adenocarcinoma.

ETIOLOGY AND PATHOPHYSIOLOGY

• Eighty-five percent of stomach cancers are adenocarcinomas with 15% lymphomas and GI stromal tumors. Adenocarcinoma is further divided into two types:
• Diffuse type—Characterized by absent cell cohesion, these tumors affect younger individuals infiltrating and thickening the stomach wall; the prognosis is poor. Several susceptibility genes have been identified for this type of cancer.
• Intestinal type—Characterized by adhesive cells forming tubular structures, these tumors frequently ulcerate.
• Tumor grade can be well (4.1%), moderate (23.1%), or poorly differentiated (54.9%), or undifferentiated (2.9%) (SEER data from 1988–2001; unknown type accounted for 15%).
• Most tumors are thought to arise from ingestion of nitrates that are converted by bacteria to carcinogens. Exogenous and endogenous factors (see “Risk Factors” below) contribute to this process.
• Exogenous sources of nitrates—Sources include foods that are dried, smoked, and salted. Helicobacter pylori infection may contribute to carcinogenicity by creating gastritis, loss of acidity, and bacterial growth
• Oncogenic pathways identified in most gastric cancers are the proliferation/stem cell, nuclear factor-κB, and Wnt/β-catenin; interactions between them appear to influence disease behavior and patient survival.
• Gastric tumors are classified for staging using the T (tumor) N (nodal involvement) M (metastases) system. Two important prognostic factors are depth of invasion through the gastric wall (less than T2 [tumor invades muscularis propria]) and presence or absence of regional lymph node involvement (N0). Changes made to the classification system in the seventh edition of the American Joint Commission’s Cancer Staging Manual for gastric cancer demonstrate better survival discrimination.
• Gastric cancer spreads in multiple ways:
• Local extension through the gastric wall to the perigastric tissues, omenta, pancreas, colon, or liver
• Lymphatic drainage through numerous pathways leads to multiple nodal group involvement (e.g., intraabdominal, supraclavicular) or seeding of peritoneal surfaces with metastatic nodules occurring on the ovary, periumbilical region, or peritoneal cul-de-sac.
• Hematogenous spread is also common with liver metastases.

RISK FACTORS

• Previous gastric surgery—As a result of alteration of the normal pH or with biopsy showing high-grade dysplasia.
• Other endogenous risk factors—Atrophic gastritis (including postsurgical vagotomized patients) and pernicious anemia are conditions that favor the growth of nitrate-converting bacteria. In addition, intestinal-type cells that develop metaplasia and possibly atypia can replace the gastric mucosa in these patients. Genetic polymorphisms (e.g., interleukin-1B-511, interleukin-1RN, and tumor necrosis factor-α) also appear to play a role. Familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer are also risk factors.
• Individuals infected with certain H. pylori bacteria (cytotoxinassociated gene A) are at increased risk of gastric adenocarcinoma (especially noncardia) and gastric mucosa-associated lymphoid tissue (MALT) lymphoma.
• Additional risk factors—Smoking, low socioeconomic class, lower educational level, exposure to certain pesticides (e.g., those who work in the citrus fruit industry in fields treated with 2,4-dichlorophenoxyacetic acid [2,4-D], chlordane, propargite, and triflurin), radiation exposure, and blood type A.

DIAGNOSIS

• Clinical features
• Asymptomatic, if superficial and/or early.
• Upper abdominal pain that ranges from vague to severe.
• Postprandial fullness.
• Anorexia and mild nausea are common
• Nausea and vomiting occur with pyloric tumors.
• Late symptoms include weight loss and a palpable mass (regional extension).
• Late complications include peritoneal and pleural effusions; obstruction of the gastric outlet; bleeding from esophageal varices or postsurgical site; and jaundice.
• Physical signs are also late features and include:
• Palpable enlarged stomach with succussion splash (splashing sound on shaking, indicative of the presence of fluid and air in a body cavity).
• Primary mass (rare).
• Enlarged liver.
• Enlarged, firm to hard, lymph nodes (i.e., left supraclavicular [Virchow]), periumbilical region (Sister Mary Joseph node), and peritoneal cul-de-sac (Blumer shelf; palpable on vaginal or rectal examination).

IMAGING AND ENDOSCOPY

• Diagnosis can be made on endoscopy (Figures 1 and 2) with biopsy of suspicious lesions. Confocal laser endomicroscopy may improve detection of early lesions.
• Urgent referral for endoscopy (within 2 weeks) is recommended for patients with dyspepsia who also have GI bleeding, dysphagia, progressive unexplained weight loss, persistent vomiting, irondeficiency anemia, epigastric mass, family history of gastric cancer (onset <50 years), or whose dyspepsia is persistent and they are older than age 55 years.
• Double-contrast radiography is an alternative to endoscopy and can detect large primary tumors but distinguishing benign from malignant disease is difficult.
• Although endoscopy is not necessary when radiography demonstrates a benign-appearing ulcer with evidence of complete healing at 6 weeks, some authors recommend routine endoscopy, biopsy, and brush cytology when any gastric ulcer is identified.
• Some gastric polyps (adenomas, hyperplastic) have malignant potential and should be removed.
• Work-up for metastases includes:
• Chest radiograph
• CT scan or MRI of the abdomen and pelvis



Figure 2: Endoscopy showing a deep ulcer with
yellow-brown exudate in the center of the mass,
consistent with cancer.

• Endoscopic sonography is useful as a staging tool when the CT scan fails to find evidence of locally advanced or metastatic disease.

LABORATORY STUDIES

• A hemoglobin or hematocrit can identify anemia, present in approximately 30% of patients.
• Electrolyte panels and liver function tests can assist in assessing the patient’s clinical state and any liver involvement.
• Carcinoembryonic antigen (CEA) is increased in about half of cases.

DIFFERENTIAL DIAGNOSIS

• Peptic ulcer—Typical symptoms include epigastric pain (described as a gnawing or burning), occurring 1 to 3 hours after meals and relieved by food or antacids. Patients may also have nausea and vomiting, bloating, abdominal distention, and anorexia. Endoscopy confirms diagnosis ( See Peptic Ulcer Disease )
• Nonulcer dyspepsia—Includes gastroesophageal reflux disease and functional dyspepsia. Classic symptoms of gastroesophageal reflux disease are heartburn (i.e., substernal pain that may be associated with acid regurgitation or a sour taste) aggravated by bending forward or lying down, especially after a large meal; individual symptoms, however, do not help to distinguish these patients from those with peptic ulcer disease. Endoscopy is considered if symptoms fail to respond to treatment (e.g., histamine-2 receptor agonist, proton pump inhibitor) or red flag signs/symptoms occur (e.g., bleeding, dysphagia, severe pain, weight loss).
• Chronic gastritis—Includes autoimmune (body-predominant) and H. pylori-related (antral-predominant) types; mucosal inflammation (primarily lymphocytes) may progress to atrophy and metaplasia. Abdominal pain and dyspepsia are common symptoms and patients may have pernicious anemia.
• Esophagitis—May be mechanical or infectious (primarily viral and fungal). Symptoms include heartburn (retrosternal wave-like pain that may radiate to the neck or jaw) and painful swallowing (odynophagia); regurgitation of sour or bitter tasting material may occur with obstruction. Barium swallow or esophagoscopy can be used to establish the diagnosis.
• Esophageal cancer—Relatively uncommon malignancy of two cell types: squamous cell cancers (largely related to smoking, excessive alcohol consumption, and other agents causing mucosal trauma) and adenocarcinomas (usually arising in the distal esophagus related to reflux disease). Symptoms include progressive dysphagia and weight loss; the diagnosis is confirmed on esophagoscopy and biopsy.

REFERENCE

• For Management and Treatment Please Read Full Information
• Ferri's Clinical Advisor
• American Family Physician Journal 
• The Washington Manual 
• Medscape
• The New England Journal of Medicine
• The Journal of American Medical Association

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