Esophageal cancer

ALSO KNOWN AS: Cancer of the esophagus

RELATED CONDITIONS: Barrett's esophagus (BE)

DEFINITION: Esophageal cancer is a disease caused by a malignant tumor that forms in the tissues of the esophagus. The two main types are adenocarcinoma and squamous cell carcinoma.

Risk factors: Gastroesophageal reflux disease (heartburn) causes about one-third of all esophageal cancers, particularly adenocarcinoma. Barrett's esophagus, in particular, is associated with an increased risk of developing esophageal cancer. Tobacco use of any form and heavy alcohol consumption are major risk factors for squamous cell carcinoma of the esophagus. Individuals who both smoke and drink excessively have a synergistic (greater than additive) risk of developing esophageal cancer. People with a diet low in fruits and vegetables also have a higher incidence of esophageal cancer, and some evidence has suggested that a high intake of refined cereals and red and processed meats may contribute to cancer risk as well. Obesity also increases the risk for adenocarcinoma, primarily through an increased incidence of acid reflux disease.

Etiology and the disease process: The esophageal wall has several layers. The inner lining is called the mucosa and has two parts: the epithelium and lamina propria. The epithelium consists of thin, flat, squamous cells. The submucosa lies under the mucosa, followed by two layers of muscle. The esophageal wall is connected to various lymph nodes.

Esophageal tumors begin in the epithelial layer. Risk factors such as tobacco use and heavy alcohol consumption may cause squamous cell carcinoma. This cancer tends to spread linearly across the submucosal layer.

Adenocarcinoma occurs largely because of chronic acid reflux and develops mainly in the lower esophagus. Acid reflux occurs when the lower esophageal sphincter between the stomach and esophagus malfunctions, allowing gastric contents to reflux back into the esophagus. Acid reflux can cause inflammation and erosion of the epithelium. When the healing occurs, the squamous cells can be replaced by epithelial cells that look like those lining the intestine. This abnormal epithelium is termed Barrett's esophagus. Although this abnormal epithelium is more resistant to acid reflux, a person with the condition is at higher risk of developing adenocarcinoma. When adenocarcinoma develops, it spreads by penetration through the total thickness of the esophageal wall. Both types of esophageal cancer can spread via the lymph nodes and eventually throughout the body.

Incidence: Over 22,000 people in the United States are diagnosed with esophageal cancer, and more than 16,000 die of the disease each year. The risk of developing esophageal cancer increases with age, with the highest incidence between ages fifty-five and seventy. Less than 15 percent of cases are diagnosed in individuals under fifty-five. Men are three to four times more likely to contract the disease than women. Squamous cell carcinoma is more common among Black Americans, while adenocarcinoma is more common among White Americans. People with Barrett's esophagus have a highly increased risk of developing adenocarcinoma, estimated between thirty and one hundred times normal. Certain regions of the world have a much higher incidence of squamous cell carcinoma, such as Iran, India, southern Africa, and northern China.

Symptoms: Esophageal cancer is often asymptomatic in its early stages. The most common symptom of esophageal cancer is dysphagia—difficulty in swallowing. Dysphagia primarily involves solid foods and can progress rapidly in severity (over weeks to months). This symptom does not usually appear until the tumor blocks at least half of the esophagus. Unintended weight loss can occur because of reduced food intake or muscle wasting from cancer-caused changes in metabolism. Other symptoms such as hoarseness, pain in the chest or throat, persistent heartburn that is resistant to medical treatment, or vomiting of blood can be caused by tumor spread.

Screening and diagnosis: Many diagnostic tests are available when a patient complains of symptoms to their physician. A barium swallow begins with a patient drinking a barium solution that coats the usually smooth surface of the esophageal lining. Subsequent X-rays can reveal early cancers that appear as small, round bumps or flat, raised areas. Advanced cancers reveal larger irregular areas and a narrowing of the esophagus.

Upper endoscopy or esophagoscopy involves a flexible viewing tube called an endoscope. The doctor can view suspicious growths and abnormalities in the esophagus and take biopsies for laboratory examination. Endoscopic ultrasound involves attaching a small ultrasound probe to the endoscope. The probe sends very sensitive sound waves that penetrate deep into tissues. This technique can determine how far the tumor has spread into the tissues.

Computed tomography is used to determine the extent (stage) of the cancer rather than an initial diagnosis. The CT scan takes many X-ray images as it rotates around the body. A computer then translates this information into thin sections of the body. The scans can show tumors in the esophagus, lymph nodes, and other organs where the cancer may have spread.

A positron emission tomography (PET) scan involves injecting a small amount of radioactive glucose tracer into the patient’s vein. The tumors show up brighter on the resultant scan. The PET scan indicates the presence or absence of malignancy based on the increased metabolic activity of tumors. PET scans can detect cancer before the anatomic and structural changes shown by tumors have time to develop. This test is valuable in detecting cancer spread to distant lymph nodes or throughout the body.

The progression of esophageal cancer is described by staging classification systems. The National Cancer Institute uses the following staging system:

• • Stage 0: Abnormal cells are detected in the mucosa or submucosa layer of the esophagus. It is also called high-grade dysplasia.
• • Stage IA: Grade-1 cancer cells have formed the mucosa or submucosa layer.
• • Stage IB: Grade-2 or grade-3 cancer cells have formed the mucosa or submucosa layer; or grade-1 cancer cells have formed in the mucosa or submucosa layer and spread into the muscle or connective tissue layer.
• • Stage IIA: Cancer has spread to the muscle layer or to connective tissue layer of the esophagus.
• • Stage IIB: Cancer may have spread to any of the first three layers of the esophagus and to nearby lymph nodes.
• • Stage III: Cancer has spread to the outer walls of the esophagus and may have spread to tissues or lymph nodes near the esophagus.
• • Stage IV: Cancer has spread to other parts of the body.

Treatment and therapy: Surgery is the most common treatment for esophageal cancer; however, there are many risks involved. The surgeon removes the cancerous part of the esophagus and may remove lymph nodes and part of the stomach if the cancer is advanced. Surgery is mainly useful for Stages 0 to I when it is most likely curative. If surgery is contemplated for Stages III and IV, it is done in combination with other therapies such as chemotherapy and radiation. Surgery is not feasible for cancers that have spread beyond the esophagus. Radiation is most effective when used with other therapies. Radiation relieves symptoms of dysphagia or in combination with chemotherapy to shrink tumors before surgery. Radiation used alone is rarely curative.

Chemotherapy helps to sensitize cancer cells to radiation, so chemotherapeutic agents are often used in combination, with or without surgery. The most effective agents for patients with squamous cell carcinoma include oxaliplatin plus fluorouracil, carboplatin plus paclitaxel, and cisplatin plus fluorouracil. Chemotherapy alone is rarely curative.

Photodynamic therapy can treat early cancers on or just under the epithelial lining. It is also used for palliative treatment to alleviate dysphagia. A non-toxic chemical is injected into the blood and allowed to accumulate in the tumor. A special laser light is focused on the tumor through an endoscope. The light converts the chemical to a toxic form that kills tumor cells.

Prognosis, prevention, and outcomes: Esophageal cancer is a very deadly cancer. Localized cases of esophageal cancer have an overall five-year survival rate of 49 percent. However, most cases of esophageal cancer are found with regional or distant metastasis, which decreases the overall five-year survival rate to 28 and 6 percent, respectively. By the time symptoms appear, the disease is incurable in most cases. Monitoring patients with gastrointestinal reflux disease for the presence of Barrett's esophagus has not been shown to improve survival rates.

The best preventive measures are to minimize the risk factors by avoiding tobacco use and heavy alcohol consumption and maintaining a healthy weight.

Bibliography

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