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Esophageal Cancer

Esophageal cancer is the sixth leading cause of cancer death worldwide. Eighty percent of deaths occur in developing countries (e.g., South Africa and China). In the United States, the incidence for the year 2000 was 12,300 new cases and 12,100 deaths; it is the seventh leading cause of cancer death in American men. In the last 25 years, there has been a significant increase in adenocarcinomas of the distal esophagus and gastroesophageal junction. In fact, between 1974 and 1994, the incidence of adenocarcinoma of the esophagus increased in white men by 450% and the incidence of squamous carcinoma of the esophagus has declined in white men by approximately 30%.

Predisposing factors

Chronic use of alcohol and smoking are associated with esophageal carcinoma. This may be due to chronic irritation of the esophageal mucosa with these agents. Other conditions with increased prevalence of esophageal carcinoma are lye strictures, achalasia, previous exposure to ionizing radiation, head and neck cancer, Plummer-Vinson syndrome, tylosis, celiac sprue, and Barrett’s epithelium.

Squamous cell carcinoma accounts for less than one half of esophageal carcinomas. Adenocarcinomas of the esophagus of the esophagus, which used to account for less than 10% of esophageal cancers, now account for greater than two thirds of all esophageal malignancies in the United States. Adenocarcinoma usually arises from metaplastic columnar epithelium (Barrett’s epithelium) and rarely from esophageal glands. Adenocarcinoma of the stomach may spread to the esophagus by extension.

Gastroesophageal reflux disease is though to be the major risk factor for esophageal adenocarcinoma. Recurrent symptoms of Gastroesophageal reflux disease seem to increase the risk of esophageal adenocarcinoma by 8-fold. The annual incidence of cancer in Barrett’s epithelium is approximately 0.8%. Anticholinergic calcium channel blockers, nitrates, and theophyllines by decreasing the lower esophageal sphincter tone, are thought to increase the risk of adenocarcinomas of the esophagus. In addition, obesity, which increases intraabdominal pressure and Gastroesophageal reflux disease, is an added risk factor.

Other less common tumors of the esophagus include lymphoma, carcinosarcoma, pseudosarcoma, squamous adenocarcinoma, melanoma, mucoepidermoid carcinoma, squamous cell papilloma, primary small cell carcinoma, verrucous carcinoma, and malignant carcinoid tumor the esophagus. Local spread from the lung and thyroid and metastasis from distant cancers may occur but is rare.

The prognosis for esophageal cancer is dismal. The 5-year survival even with the earliest stages of cancer is only 50% to 80% and with lymph node involvement it drops to below 25%. With locally advanced esophageal cancer the survival drops to 5% to 10% (with radiation or surgery alone) and with chemoradiation and surgery, it may be 25% to 27%.

Regardless of the histologic type, esophageal cancer usually is disseminated at the time of diagnosis. The rich esophageal lymphatics allow for early and extensive spread of the disease longitudinally and to contiguous organs. Esophagobronchial or esophagopleural fistulas may form and manifest as recurrent pneumonia or abscess. Erosion into the aorta may result in exsanguination.

Clinical features

Progressive dysphagia for less than a year, first with solids then with semisolids and liquids, is the most common symptom. Substernal pain, usually steady, radiating to the back may also be present and may suggest periesophageal spread of the tumor. Most patients complain of anorexia and profound weight loss. Patients may have iron-deficiency anemia from blood loss from the lesion, but brisk bleeding is rare. Hoarseness may result from involvement of the recurrent laryngeal nerve. If the lesion is obstructive, patients may aspirate esophageal contents.

Diagnosis

A barium swallow is usually the first noninvasive test ordered to establish the diagnosis of esophageal carcinoma. A double-contrast study may be helpful in identifying small, plaquelike lesions. The usual finding is an irregular luminal narrowing. There may be a ridge or shelf at the superior portion of the tumor. However, the differentiation of the tumor from a benign peptic stricture can be extremely difficult by radiography.

Endoscopy

Fiberoptic endoscopy allows direct localization and inspection of the lesion. Retroflexion of the endoscope in the fundus of the stomach allows visualization of lesions at the esophagogastric junction and cardia, which could not be done by rigid scopes. Direct biopsies and brushings provide tissue for histologic and cytologic examination.

Computed tomography is very helpful in determining the extent and spread of extramucosal tumor.

Endoscopic ultrasonography. Endoscopic ultrasonography, with its unique ability to define the gut wall in detail, offers the most accurate method for evaluating the depth of esophageal cancer invasion and detecting abnormal regional lymph nodes. Because esophageal carcinoma originates in the mucosa and progressively invades deeper layers of the wall, the TNM classification recommended by the International Union Against Cancer and the American Joint Committee on Cancer lends itself to accurate staging with endoscopic ultrasonography. T indicates depth of primary tumor invasion, N indicates spread of cancer to regional lymph nodes, and M indicates distant metastases.

Magnetic resonance imaging is a technique in longitudinal and cross-sectional body imaging. Currently, it offers no advantage over computed tomography in detecting infiltrating growth.

Treatment

The therapy for carcinoma of the esophagus is determined by the stage of the disease. The mainstay of therapy has been surgery, with or without radiotherapy and chemotherapy. Inoperable tumors have been treated by radiotherapy, because squamous carcinoma of the esophagus is relatively radiosensitive. Chemotherapy alone has not been very successful. Treatment protocols combining chemotherapy and radiation therapy before and after surgery offer somewhat better results than single-modality therapy. Most successful chemotherapeutic agents are the combination of cisplatin, 5-fluorouracil, paclitaxel, irinotecan hydrochloride, vinorelbine tartrate, and gemcitabine hydrochloride preoperatively and as neoadjuvant chemotherapy.

Surgery

Total esophagectomy is the surgical procedure of choice. Patients with lesions of the lower third that are less than 5 cm seem to do better. Because the cure rate has been so dismally low with «curative» surgery, palliative resection has been used to alleviate symptoms and allow patients to swallow.

The morbidity and mortality with a large thoracotomy are still very high in these patients. The esophageal resection and esophagogastric anastomosis may be done with a combined abdominal incision and a right thoracotomy. If the lesion is low enough, an abdominal approach may suffice. For most lesions, it is preferred to resect the involved portion of the esophagus with wide margins, bring the stomach into the chest, and create an anastomosis with the remaining esophagus. Colonic or jejunal segment interposition carries a high complication rate. For purposes of palliation, the stomach may be anastomosed to the esophagus in a side-to-side fashion to bypass the obstructed area.

Radiation therapy

Radiation therapy for squamous cell carcinoma of the esophagus has been used for attempted cure with unsatisfactory results. It is used in protocols before or after surgery and for palliation.

Presurgical radiation therapy alone has not been found to increase the cure rate.

Adenocarcinomas are resistant to radiation therapy.

Other palliative measures

  • Mechanical dilatation. When surgery and radiation therapy are contraindicated, or when these treatments have failed, mechanical dilatation of the esophageal lumen may be attempted with Savary or balloon dilators under endoscopic guidance. Because the risk of esophageal perforation is high in these patients, the dilatation should be done slowly and with great care.
  • Tube placement. If it becomes difficult to maintain a lumen at the area of the tumor, a stent (plastic or metal) may be placed in the lumen endoscopically. These tubes may also be used to close off, at least temporarily, a tracheoesophageal fistula. These tubes may erode into the esophageal wall, causing ulceration, bleeding, and perforation.

Yag-laser therapy has been found to be quite effective in palliation of patients with advanced obstructing esophageal tumors. These masses may be «pared down» by the laser to open the lumen. Lasers may also be useful in the treatment of very early lesions. Additional controlled studies need to be done using this technique.

Injection necrosis of fungating esophageal cancer can be accomplished with intratumoral injection of absolute alcohol or ethylene glycol with endoscopic visualization. In instances of luminal narrowing, malignant strictures may be dilated first, then injected concentrically to additionally «open up» the lumen.

These palliative measures are usually repeated as needed with progressive, repeated growth of the tumor.

Selection of therapy. Presently, the optimal therapy for esophageal cancer is unclear. A strong case can be made for establishing comparable diagnostic staging criteria and treating newly diagnosed patients according to well-designed, established research protocols whenever possible. If the use of research protocols is not feasible, a reasonable approach is to use resectional surgery for «resectable» tumors in the distal third of the esophagus (T1-3 N1) with pre- and neoadjuvant chemoradiation therapy. For patients who are poor candidates for surgery or who have obstructing tumors, one or more of the listed palliative measures may be used.

Prevention and surveillance. Patients with recurrent symptoms of Gastroesophageal reflux disease are recommended to have endoscopy and biopsies for the diagnosis of Barrett’s esophagus. Endoscopic surveillance will allow the diagnosis of earlier stage tumors and allow for improved survival. Patients should be advised to stop smoking and the use of alcohol in moderation. Current recommendations for patients with Barrett’s esophagus is biannual endoscopic surveillance and annually if there is low-grade dysplasia. Patients with high-grade dysplasia are recommended to undergo esophagectomy or mucosal ablation with photodynamic therapy.

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