Esophageal cancer

The most common malignant tumor of the esophagus is squamous cell carcinoma, followed by adenocarcinoma. Symptoms of esophageal cancer include progressive dysphagia and weight loss. The diagnosis of esophageal cancer is made by endoscopy, followed by CT and endoscopic ultrasound to verify the stage of the process. Treatment of esophageal cancer depends on the stage and generally includes surgery with or without chemotherapy and radiation therapy. Long-term survival is observed in a small percentage of cases, except for patients with limited disease.

Each year in the United States, approximately 13,500 cases of esophageal cancer are diagnosed and 12,500 deaths occur.

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What causes esophageal cancer?

Squamous cell carcinoma of the esophagus

Approximately 8,000 cases are diagnosed in the United States each year. The disease is more common in parts of Asia and South Africa. In the United States, squamous cell carcinoma is 4 to 5 times more common among blacks than whites, and 2 to 3 times more common among men than women.

The primary risk factors are alcohol abuse and tobacco use in any form. Other risk factors include achalasia, human papillomavirus, chemical burn with alkali (resulting in stricture), sclerotherapy, Plummer-Vinson syndrome, irradiation of the esophagus and esophageal membrane. Genetic factors are unclear, but in patients with keratoderma (palmar and plantar hyperkeratosis), an autosomal dominant disorder, esophageal cancer occurs in 50% of patients at age 45 and in 95% of patients at age 55.

Adenocarcinoma of the esophagus

Adenocarcinoma affects the distal esophagus. The incidence is increasing; it accounts for 50% of esophageal cancers in whites and is four times more common in whites than in blacks. Alcohol is not a significant risk factor, but smoking contributes to the development of the tumor. Adenocarcinoma of the distal esophagus is difficult to differentiate from adenocarcinoma of the gastric cardia due to tumor invasion into the distal esophagus.

Most adenocarcinomas develop in Barrett's esophagus, which is a consequence of chronic gastroesophageal reflux disease and reflux esophagitis. In Barrett's esophagus, a columnar, glandular, enteric-like mucosa replaces the stratified squamous epithelium of the distal esophagus during the healing phase of acute esophagitis.

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Other malignant tumors of the esophagus

Rarer malignancies include spindle cell carcinoma (a poorly differentiated variant of squamous cell carcinoma), verrucous carcinoma (a well-differentiated variant of squamous cell carcinoma), pseudosarcoma, mucoepidermoid carcinoma, adenosquamous cell carcinoma, cylindroma (adenocystic carcinoma), primary oat cell carcinoma, choriocarcinoma, carcinoid tumor, sarcoma, and primary malignant melanoma.

Metastatic esophageal cancer accounts for 3% of esophageal cancer. Melanoma and breast cancer can metastasize to the esophagus; other sources include cancers of the head and neck, lung, stomach, liver, kidney, prostate, testicle, and bone. These tumors typically involve the loose connective tissue stroma around the esophagus, whereas primary esophageal cancers begin in the mucosa or submucosa.

Symptoms of Esophageal Cancer

The early stages of esophageal cancer are usually asymptomatic. Dysphagia occurs when the lumen of the esophagus becomes smaller than 14 mm. The patient first has difficulty swallowing solids, then semisolids, and finally liquids and saliva; this steady progression suggests a process of malignancy rather than spasm, benign Schatzki ring, or peptic stricture. Chest pain may be present, usually radiating posteriorly.

Weight loss, even in patients with a good appetite, is a nearly universal finding. Compression of the recurrent laryngeal nerve may result in vocal cord paralysis and hoarseness. Compression of the sympathetic nerves may result in Horner's syndrome, and compression of the nerve elsewhere may cause back pain, hiccups, or diaphragmatic paralysis. Pleural involvement with pleural effusion or pulmonary metastasis may cause dyspnea. Intraluminal tumor growth may cause odynophagia, vomiting, hematemesis, melena, iron deficiency anemia, aspiration, and cough. Fistulas between the esophagus and tracheobronchial tree may result in lung abscess and pneumonia. Other abnormalities that may be seen include superior vena cava syndrome, cancerous ascites, and bone pain.

Lymphatic metastasis to the internal jugular, cervical, supraclavicular, mediastinal, and celiac nodes is characteristic. The tumor usually metastasizes to the lungs and liver and occasionally to distant sites (e.g., bone, heart, brain, adrenal glands, kidneys, peritoneum).

Diagnosis of esophageal cancer

There are currently no screening tests. Patients with suspected esophageal cancer should undergo endoscopy with cytology and biopsy. Although a barium swallow may demonstrate an obstructive lesion, endoscopy is necessary for biopsy and tissue examination.

Patients with identified cancer should undergo chest CT and abdominal CT to determine the extent of tumor spread. If there are no signs of metastasis, endoscopic ultrasound should be performed to determine the depth of tumor invasion into the esophageal wall and regional lymph nodes. The data obtained help determine therapy and prognosis.

Basic blood tests should be performed, including complete blood count, electrolytes, and liver function tests.

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Treatment of esophageal cancer

Treatment of esophageal cancer depends on the stage of tumor growth, size, location and the patient's wishes (many refrain from aggressive treatment).

General principles of treatment of esophageal cancer

In patients with stages 0.1 and B, good results are achieved with surgical resection; chemotherapy and radiotherapy are not required. In stages IIb and III, surgical treatment alone is insufficient due to low survival; the effectiveness of surgery and survival are increased by preoperative (add-on) use of radiotherapy and chemotherapy to reduce the tumor volume before resection. Palliative combined treatment of esophageal cancer, including radiotherapy and chemotherapy, is indicated for patients who refuse surgery or have contraindications. The effectiveness of radiotherapy or chemotherapy alone is very low. Patients with stage IV disease require palliative therapy only and do not require surgical treatment.

Esophageal Cancer Stages

Stage	Tumor (maximum invasion)	Metastases to regional lymph nodes	Distant metastases
0	Tis	N0	M0
I	T1	N0	M0
IIa, b	T2 or T3	N0	M0
III	T3 or T4	N1	M0
IV	Any T	Any N	M1

¹ TNM classification: Tis - carcinoma in situ; T1 - lamina propria or submucosa; T2 - muscularis propria; T3 - adventitia; T4 - adjacent structures. N0 - none; N1 - present. M0 - none; M1 - present.

After treatment, patients are shown screening repeat endoscopic and CT examinations of the neck, chest and abdomen every 6 months for 3 years, and then once a year.

Patients with Barrett's esophagus require intensive long-term treatment for gastroesophageal reflux disease and endoscopic surveillance for malignant transformation over a 3- to 12-month interval, depending on the degree of metaplasia.

Surgical treatment of esophageal cancer

Treatment requires en bloc resection with removal of the entire tumor at the level of normal tissue distal and proximal to the tumor, as well as all potentially affected lymph nodes and part of the proximal stomach containing the distal lymphatic drainage pathway. The operation requires additional mobilization of the stomach upward with the formation of an esophagogastrostomy, mobilization of the small or large intestine. Pyloroplasty ensures mandatory drainage of the stomach, since removal of the esophagus is necessarily accompanied by bilateral vagotomy. Such extensive surgery is poorly tolerated by patients over 75 years of age, especially with concomitant underlying cardiac or pulmonary pathology [ejection fraction less than 40%, or FE^ (forced expiratory volume in 1 second) < 1.5 L/min]. Overall, operative mortality is approximately 5%.

Complications of the procedure include anastomotic leakage, fistulas and strictures, biliary gastroesophageal reflux, and dumping syndrome. Burning retrosternal pain due to bile reflux after distal esophagectomy may be more severe than the usual symptoms of dysphagia and may require reconstructive surgery with Roux-en-Y jejunostomy to divert bile. Interposition of a segment of small or large bowel into the chest cavity may cause disruption of the blood supply, torsion, ischemia, and gangrene of the bowel.

External beam radiation therapy

Radiation therapy is usually used in combination with chemotherapy in patients with questionable surgical efficacy or with comorbidities. Radiation therapy is contraindicated in patients with tracheoesophageal fistulas because tumor shrinkage leads to fistula enlargement. Similarly, in patients with vascular invasion, tumor shrinkage may lead to massive bleeding. In the early stages of radiation therapy, edema may lead to deterioration of esophageal patency, dysphagia, and pain when swallowing. This problem may require esophageal dilation or preliminary placement of a percutaneous gastrostomy tube for feeding. Other side effects of radiation therapy include nausea, vomiting, anorexia, malaise, esophagitis, excess mucus production in the esophagus, xerostomia (dry mouth), strictures, radiation pneumonitis, radiation pericarditis, myocarditis, and myelitis (inflammation of the spinal cord).

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Chemotherapy

Tumors are only poorly responsive to chemotherapy. The effect (defined as a tumor size reduction of >50%) is observed in 10-40%, but overall the effectiveness is insignificant (slight tumor shrinkage) and temporary. No differences in drug effectiveness are noted.

Cisplatin and 5-fluorouracil are commonly used in combination, although several other drugs, including mitomycin, doxorubicin, vindesine, bleomycin, and methotrexate, are also quite active against squamous cell carcinoma.

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Palliative treatment of esophageal cancer

Palliative treatment of esophageal cancer aims to reduce esophageal obstruction sufficiently to allow oral feeding. Symptoms of esophageal obstruction can be significant and include salivation and recurrent aspiration. Treatment options include dilation procedures (bougienage), oral stent placement, radiation therapy, laser photocoagulation, and photodynamic therapy. In some cases, cervical esophagostomy with jejunostomy for feeding is required.

The effectiveness of esophageal dilation lasts little more than a few days. A flexible metal stent loop is more effective in maintaining esophageal patency. Some plastic-coated models may be used to close tracheoesophageal fistulas, and some models may have a valve to prevent reflux if the stent needs to be placed near the lower esophageal sphincter.

Endoscopic laser photocoagulation may be effective in dysphagia, as it burns a central canal through the tumor and can be repeated if necessary. Photodynamic therapy involves the administration of sodium porfimer, a hematoporphyrin derivative that is taken up by the tissue and acts as an optical sensitizer. When activated by a laser beam directed at the tumor, this substance releases cytotoxic singlet oxygen, which destroys tumor cells. Patients receiving this treatment must avoid sun exposure for up to 6 weeks after treatment, as the skin also becomes sensitive to light.

Supportive care for esophageal cancer

Nutritional support with enteral or parenteral nutrition increases the sustainability and feasibility of all treatment options. Endoscopic or surgical intubation for feeding provides longer-term nutrition in case of esophageal obstruction.

Because almost all cases of esophageal cancer are fatal, end-of-life care should focus on reducing the effects of the disease, especially pain and inability to swallow. Most patients will require significant doses of opiates at some point. Patients should be advised to make management decisions during the course of the disease and to record their wishes if the disease becomes advanced.

What is the prognosis for esophageal cancer?

Esophageal cancer has a variable prognosis. It depends on the stage of the disease, but is generally not very good (5-year survival: less than 5%) because patients present with advanced disease. In patients with cancer limited to the mucosa, survival is approximately 80%, which decreases to less than 50% with submucosal involvement, 20% with the spread of the process to the muscularis propria, 7% with involvement of adjacent structures, and less than 3% with distant metastases.