January 16, 2007

Esophageal Cancer

Synonyms and related keywords: esophagus cancer, Barrett epithelium, Barrett's epithelium, Barrett esophagus, Barrett's esophagus, gastrointestinal reflux disease, GERD, esophageal adenocarcinoma, esophagus adenocarcinoma, esophagus carcinoma, esophageal carcinoma, reflux disease, squamous cell carcinoma, esophageal cancer


Background: Esophageal carcinoma was well described at the beginning of the 19th century, and the first successful resection was performed in 1913 by Frank Torek. In the 1930s, Ohsawa in Japan and Marshall in the United States were the first to perform successful 1-stage transthoracic esophagectomies with continent reconstruction.

Pathophysiology: Esophageal carcinoma arises in the mucosa. Subsequently, it tends to invade the submucosa and the muscular layer and, eventually, contiguous structures such as the tracheobronchial tree, the aorta, or the recurrent laryngeal nerve. The tumor also tends to metastasize to the periesophageal lymph nodes and, eventually, to the liver, lungs, or both.


  • In the US: In the United States, esophageal carcinoma accounts for 10,000 to 11,000 deaths per year. Adenocarcinoma of the esophagus has the fastest growing incidence rate of all cancers in the United States. The incidence of esophageal carcinoma is approximately 3-6 cases per 100,000 persons, although certain endemic areas appear to have higher per-capita rates. The age-adjusted incidence is 5.8 cases per 100,000 persons.

    The epidemiology of esophageal carcinoma has changed markedly over the past several decades in the United States. Until the 1970s, squamous cell carcinoma was the most common type of esophageal cancer (90-95%). It was located in the thoracic esophagus and affected mostly African American men who had a long history of smoking and alcohol consumption. Over the last 2 decades, the incidence of adenocarcinoma of the distal esophagus and gastroesophageal junction has progressively increased. Currently, it accounts for more than 50% of all new cases of esophageal cancer. Unlike squamous cell carcinoma, it affects mostly white men, and its pathogenesis is linked to gastroesophageal reflux disease (GERD) and the development of Barrett epithelium.

  • Internationally: Esophageal cancer is the seventh leading cause of cancer death worldwide. Incidence of esophageal carcinoma can be as high as 30-800 cases per 100,000 persons in particular areas of northern Iran, some areas of southern Russia, and northern China. Unlike in the United States, squamous cell carcinoma is responsible for 95% of all esophageal cancer worldwide.

Sex: Esophageal cancer generally is more common in men than in women, with a male-to-female ratio of 7:1.

Age: Esophageal cancer occurs most commonly during the sixth and seventh decades of life.





    • In 1952, Morson and Belcher first described a patient with adenocarcinoma of the esophagus arising in a columnar epithelium with goblet cells. In 1975, Naef et al emphasized the malignant potential of Barrett esophagus. With the premalignant nature of Barrett esophagus well established, many investigators have searched for markers of esophageal carcinoma that could facilitate earlier diagnosis and follow-up of tumor recurrence.
    • The risk of adenocarcinoma among patients with Barrett metaplasia has been estimated to be 30-60 times that of the general population.
    • The oncosuppressor gene TP53 and various oncogenes, particularly erb-b2, have been studied as potential markers. Casson and colleagues identified mutations in the TP53 gene in patients with Barrett epithelium associated with adenocarcinoma.
    • A nationwide population-based case-control study performed in Sweden found an odds ratio of 7.7 (95% confidence interval, 5.3-11.4) for adenocarcinoma among persons with recurrent symptoms of reflux, as compared with persons without such symptoms, and an odds ratio of 43.5 (95% confidence interval, 18.3-103.5) among patients with long-standing and severe symptoms of reflux.


Esophageal Stricture

Other Problems to be Considered:

Peptic strictures due to reflux
Benign esophageal tumors


Lab Studies:

Imaging Studies:

  • Performing esophagogastroduodenoscopy allows direct visualization and biopsies of the tumor.
  • Endoscopic ultrasound is the most sensitive test to help determine the depth of penetration of the tumor (T staging) and the presence of enlarged periesophageal lymph nodes (N staging).
  • Abdominal and chest CT scans are useful to help exclude the presence of metastases (M staging) to the lungs and liver and may be useful to help determine if adjacent structures have been invaded.
  • Bronchoscopy is indicated for cancers of the middle and upper third of the thoracic esophagus to help exclude invasion of the trachea or bronchi.
  • Bone scan is indicated in patients with complaints suggestive of bone metastases.
  • Laparoscopy and thoracoscopy have a greater than 92% accuracy in staging regional nodes.
  • A new modality for staging is positron emission tomography scanning, which can help elucidate hypermetabolic foci of disease activity.


Medical Care: Nonoperative therapy is usually reserved for patients who have esophageal carcinoma and are not candidates for surgery. The goal of therapy for these patients is palliation of dysphagia, allowing them to eat. A single best method of palliation cannot be applied to every situation. Most patients require more than one palliative method to sustain lumen patency during the course of their disease.

Surgical Care: Esophageal resection (esophagectomy) remains a crucial part of the treatment of esophageal cancer. It is used in patients who are considered candidates for surgery. It no longer is used for palliation of symptoms because other treatment modalities now are available for relieving dysphagia (see Medical Care). An esophagectomy can be performed by using an abdominal and a cervical incision with blunt mediastinal dissection through the esophageal hiatus (ie, transhiatal esophagectomy [THE]) or by using an abdominal and a right thoracic incision (ie, transthoracic esophagectomy [TTE]).

  • THE offers the advantage of avoiding a chest incision, which can be a prolonged cause of discomfort and can further aggravate the condition of patients with compromised respiratory function.
    • After removal of the esophagus, continuity of the gastrointestinal tract is usually reestablished by using the stomach.
    • Some authors have questioned the validity of THE as a cancer operation because part of the operation is not performed under direct vision and fewer lymph nodes are removed compared to TTE. However, many retrospective and 2 prospective studies have shown no difference in survival between the operations, suggesting that the type of operation is not the factor influencing survival but, rather, the stage of the cancer at the time the operation is performed.
    • The morbidity associated with the operation is due mostly to cardiac, respiratory, and septic complications. As with other complex operations (eg, cardiac operations, resection of the pancreas or liver), a low mortality rate is achieved in centers with personnel who have more clinical experience (ie, those in high-volume centers). The better results (as compared to low-volume centers) are due to a team approach, during which expert surgeons work with intensivists, cardiologists, pulmonologists, radiologists, and nurses who have experience and expertise. For instance, in California from 1990-1994, only 5 centers had a mortality rate of 5% or less for esophageal resection for cancer, while the average mortality rate in the state was approximately 18%.
  • Relevant anatomy includes the following:
    • The esophagus is a muscular tube that extends from the level of the seventh cervical vertebra to the 11th thoracic vertebra. The esophagus can be divided into 3 anatomic parts: the cervical esophagus, the thoracic esophagus, and the abdominal esophagus.
    • The blood supply of the cervical esophagus is derived from the inferior thyroid artery, while the blood supply for the thoracic esophagus comes from the bronchial arteries and the aorta. The abdominal esophagus is supplied by branches of the left gastric artery and inferior phrenic artery.
    • Venous drainage of the cervical esophagus is through the inferior thyroid vein, while the thoracic esophagus drains via the azygous vein, the hemiazygous vein, or the bronchial veins. The abdominal esophagus drains through the coronary vein.
    • The esophagus is characterized by a rich network of lymphatic channels in the submucosa that can facilitate the longitudinal spread of neoplastic cells along the esophageal wall. Lymphatic drainage is to cervical nodes, tracheobronchial and mediastinal nodes, and gastric and celiac nodes.
  • Indications for surgery include the following:
    • Diagnosis of esophageal cancer must be made in a patient who is a candidate for surgery.
    • Surgery is indicated when high-grade dysplasia is present in a patient with Barrett esophagus. As many as 50-70% of such patients are found to have cancer when the esophagus is resected.
  • Contraindications to surgery include the following:
    • Metastasis to N2 nodes (ie, celiac, cervical, or supraclavicular lymph nodes) or solid organs (eg, liver, lungs) is a contraindication.
    • Invasion of adjacent structures (eg, recurrent laryngeal nerve, tracheobronchial tree, aorta, pericardium) is a contraindication.
    • Severe associated comorbid conditions (eg, cardiovascular disease, respiratory disease) can decrease a patient's chances of surviving an esophageal resection.
    • Cardiac function and respiratory function are carefully evaluated preoperatively. A forced expiratory volume in 1 second of less than 1.2 L and a left ventricular ejection fraction of less than 0.4 are relative contraindications to the operation.
  • TTE involves the following:
    • The patient is placed supine on the operating room table. An arterial line, a central venous catheter, a Foley catheter, and a dual-lumen endotracheal tube are placed. Preoperative antibiotics are administered. An upper midline incision is made.
    • After exploring the peritoneal cavity for metastatic disease (if metastases are found, the operation is not continued), the stomach is mobilized. The right gastric and the right gastroepiploic arteries are preserved, while the short gastric vessels and the left gastric artery are divided.
    • Next, the gastroesophageal junction is mobilized, and the esophageal hiatus is enlarged. A pyloromyotomy is performed, and a feeding jejunostomy is placed for postoperative nutritional support.
    • After closure of the abdominal incision, the patient is repositioned in the left lateral decubitus position and a right posterolateral thoracotomy is performed in the fifth intercostal space.
    • The azygos vein is divided to allow full mobilization of the esophagus. The stomach is delivered into the chest through the hiatus and is then divided approximately 5 cm below the gastroesophageal junction.
    • An anastomosis (hand-sewn or stapled) is performed between the esophagus and the stomach at the apex of the right chest cavity. Then, the chest incision is closed.
  • THE involves the following:
    • Preoperative details are similar to those of TTE, with the exception of a single rather than a double-lumen endotracheal tube. The neck is prepared in the operative field.
    • The abdominal part of the operation is identical to the TTE; however, dissection of the esophagus is performed through the enlarged esophageal hiatus without opening the right chest. The esophagus is mobilized in this fashion all the way to the thoracic inlet.
    • Then, a 6-cm incision is made in the left side of the neck. The internal jugular vein and carotid artery are retracted laterally, and the esophagus is identified and isolated posterior to the airway. To prevent injury to the left recurrent laryngeal nerve, no mechanical retractors are used to retract the trachea.
    • Next, after resection of the proximal stomach and thoracic esophagus, the remaining stomach is pulled up through the posterior mediastinum until it reaches the remaining esophagus at the cervical level.
    • Then, a hand-sewn anastomosis is performed, and a small drain is placed in the neck alongside the anastomosis. The abdominal and neck incisions are closed.
  • Advantages of minimally invasive surgery include the following:
    • The use of laparoscopic or thoracoscopic techniques has revolutionized the treatment of benign esophageal disorders such as achalasia and GERD.
    • When compared to open surgery, the hospital stay is shorter, the postoperative discomfort is reduced, and the recovery time is much faster. In the near future, these techniques might find a place in the treatment of esophageal cancer, reducing the morbidity due to cardiac and respiratory complications.


Further Inpatient Care:

Further Outpatient Care:



  • THE and TTE have equivalent survival rates.
  • Squamous cell carcinoma and adenocarcinoma, stage-by-stage, have equivalent survival rates.

Patient Education:

  • For excellent patient education resources, visit eMedicine's Esophagus, Stomach, and Intestine Center. Also, see eMedicine's patient education article, Cancer of the Esophagus.


Special Concerns:

  • Follow-up of patients with Barrett esophagus includes the following:
    • For metaplasia, the common recommendation is to perform routine endoscopy every 12-24 months because no evidence suggests that either medical or surgical therapy can stop the progression to high-grade dysplasia and cancer. In addition, routine endoscopy can detect a tumor at an early stage, thereby increasing the possibility of a curative resection.
    • For high-grade dysplasia, the protocol suggested by investigators at the University of Washington in Seattle proposes endoscopy every 3 months with jumbo forceps and 4-quadrant biopsy samples taken at 1-cm intervals. The rationale is to avoid esophagectomy in patients who will not progress to cancer, based on the belief that this protocol will identify carcinoma in situ before it becomes invasive with lymph node metastases. This protocol has 2 major problems, as follows:
      • The protocol can rarely be followed in the average clinical practice, ie, outside of tertiary care centers, because of poor patient compliance and reluctance by the gastroenterologists to perform such extensive biopsies. In addition, there is a risk of missing an in situ lesion. Once the tumor is invasive, lymph node metastases are common and the chance of cure is lost.
      • When an esophagectomy is performed for high-grade dysplasia detected using endoscopy, adenocarcinoma is found in approximately 40% of cases (range of 30-73%).
    • Based on these considerations, the authors and others strongly recommend that esophagectomy be performed once high-grade dysplasia is detected. The operation must be performed by experienced surgeons in high-volume centers in order to keep the mortality rate at less than 5%.

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