The esophagus is the muscular tube that conveys food from the back of the throat to the stomach. It is located in the chest behind the sternum and the trachea, the main breathing tube leading to the lungs. The esophagus joins the stomach at the diaphragm, which is the breathing muscle separating the chest and lungs from the abdomen. The connection of the esophagus to the stomach at the diaphragm is called the gastro-esophageal junction. The gastro-esophageal junction serves as a one-way valve to keep stomach contents from being refluxed or regurgitated back into the esophagus.
Once food has emptied into the stomach, it is mixed with enzymes and acids from the stomach and gall bladder to enhance digestion. If stomach contents reflux or regurgitate back into the esophagus the surface lining can be damaged due to the acidity of these contents. One symptom of regurgitation of stomach contents into the lower esophagus is heartburn, which is a common condition occurring in approximately 10% of all people. Heartburn is often associated with a “hiatal hernia,” which is a condition where the upper part of the stomach pushes up above the diaphragm and into the chest. Normally, the esophagus is lined with squamous epithelial cells; however, when reflux occurs, these cells are replaced by columnar epithelium, which is prone to develop a type of cancer called adenocarcinoma. This phenomenon is known as Barrett’s esophagus.
Esophageal cancer is relatively common and is very deadly. Each year in the United States, there are roughly 17,000 new cases of esophageal cancer and 15,000 deaths from the disease.1
Most cancers of the upper two thirds of the esophagus arise from squamous cells and are called squamous cell or epidermoid cancers. Cancers of the lower esophagus most often arise from columnar epithelium and are called adenocarcinomas. In the recent past, squamous cell cancers made up more than 80% of all esophageal cancers. Over the past two decades, there has been a dramatic increase in the incidence of adenocarcinomas, which now account for one-third to one-half of all esophageal cancers. Most of the adenocarcinomas of the lower esophagus are thought to arise in the setting of Barrett’s esophagus, which is discussed below. Thus, the recent increase in the overall incidence of esophageal cancer is almost entirely due to the increase in adenocarcinomas.
Outcomes of treatment for squamous cell cancer and adenocarcinoma of the esophagus are very similar, except for the responsiveness of the cancer to some chemotherapy drugs. The results of treatment of squamous cell cancer and adenocarcinoma are included together unless otherwise specified.
The 5-year survival rate for all patients diagnosed with esophageal cancer is approximately 5%, with most survivors having cancer that has not spread outside the esophagus (stage 0-II). This low survival is due to a combination of factors including advanced age, with an average age of 69 years at diagnosis; the presence of local and distant spread of cancer at diagnosis; associated heart and lung disease and the fact that most patients have some minimal residual cancer remaining after primary treatment with surgical resection. In addition, the anatomical location of the esophagus makes surgical resection of cancer a technically difficult operation, with death rates following surgery ranging from 3-19% in theUnited States. Since it is a difficult surgery, esophagectomy (removal of the esophagus) should only be performed by a skilled team of surgeons, anesthesiologists and nurses.
HISTOLOGICAL TYPES OF ESOPHAGEAL CANCER
Barrett’s Esophagus: Barrett’s esophagus involves the abnormal presence of columnar epithelium in the surface lining of the lower esophagus, which should only contain squamous cells. This abnormal epithelium is prone to develop pre-cancerous, or pre-malignant, changes called dysplasia, which are further characterized as either low-grade or high-grade. Dysplasia is a term for abnormalities in cells that do not appear normal under the microscope, but are not yet characteristic of invasive cancer. Currently, physicians and researchers believe that under certain conditions, dysplasia in the esophagus may be reversed and the subsequent development of cancer prevented.
Squamous Cell Cancer: Squamous cell cancer arises from normal squamous epithelium of the esophagus.
Adenocarcinoma: Adenocarcinoma is a type of cancer that arises from columnar epithelium that is characteristic of the stomach and intestines. Adenocarcinoma of the lower esophagus is thought to usually arise from Barrett’s esophagus.
STAGING OF ESOPHAGEAL CANCER
If possible, it is important to determine the extent of cancer before treatment in order to select the best treatment option. Of particular concern is the presence of cancer in lymph nodes, spread of cancer to distant sites or local extension of cancer into surrounding structures, which might make attempts to remove all cancer with surgical resection impossible. Unfortunately, in many cases the true extent of spread of cancer can only be determined by surgical resection. Frequently, more advanced cancer is found at surgery than was detected by clinical tests.
Routine Staging: All patients with esophageal cancer undergo a routine chest x-ray examination and a barium swallow under fluoroscopy (direct x-ray examination of the esophagus) as part of initial staging evaluation. All patients have computerized tomography (CT) scans of the chest, upper abdomen and possibly the neck. Unfortunately, there can be considerable error in CT scanning in detecting the extent of local spread of esophageal cancer, but accuracy for detecting distant spread (metastasis) is good.
Esophagoscopy: An esophagoscopy is an examination performed through an endoscope, which is a flexible tube inserted through the esophagus that allows the physician to visualize, photograph and biopsy (sample) the cancer. All patients undergo an esophagoscopy with biopsy to determine the histology or appearance of the cancer under the microscope.
Thoracoscopy: A thoracoscopy is another procedure performed through an endoscope to examine the chest in order to determine the extent of spread of cancer in the chest.
Laparoscopy: Laparoscopy is a procedure that involves the insertion of an endoscope through a small incision in the abdomen. Laparoscopy is an important tool for staging and has proven to be more reliable than CT scanning in detecting spread of cancer to the liver and the lining of the abdomen (peritoneum).
Bronchoscopy: Bronchoscopy refers to the examination of the lungs and can be helpful in identifying involvement of the trachea when the primary cancer is advanced and located in the upper part of the esophagus.
Endosonography: Endosonography refers to an ultrasound test performed through an endoscope. Ultrasound tests utilize sound waves to detect different densities of tissue, including cancer. Endosonography can detect spread of cancer into various layers of the stomach, adjacent organs and lymph nodes better than CT scanning.
Positron emission tomography (PET): Positron emission tomography (PET) scanning has also been used to improve the detection of cancer in lymph nodes. One characteristic of living tissue is the metabolism of sugar. Prior to a PET scan, a substance containing a type of sugar attached to a radioactive isotope (a molecule that spontaneously emits radiation) is injected into the patient’s vein. The cancer cells “take up” the sugar and attached isotope, which emits positively charged, low energy radiation (positrons). The positrons react with electrons in the cancer cells, which creates the production of gamma rays. The gamma rays are then detected by the PET machine, which transforms the information into a picture. If no gamma rays are detected in the scanned area, it is unlikely that the mass in question contains living cancer cells. In one clinical study, PET scanning detected 85% of lymph nodes involved with cancer, which was significantly better than the detection rate with CT scanning.
Barrett’s Esophagus: There are essentially three categories of abnormal changes in the surface lining of the lower esophagus: (1) Barrett’s esophagus (presence of columnar epithelium) without other changes, (2) Barrett’s esophagus with low-grade dysplasia and (3) Barrett’s esophagus with high-grade dysplasia.
Stage 0: Cancer in situ is cancer that is limited to the surface epithelium. There can be extensive spread along the surface of the lining of the esophagus, but there is no spread of cancer below the surface into lymph nodes or to distant sites.
Stage I: Cancer invades beneath the surface lining, but does not invade the muscular part of the wall of the esophagus and there is no spread to lymph nodes or distant spread of cancer.
Stage II: Cancer invades into or through the muscle of the wall of the esophagus, but not into local structures (IIA). When there is regional lymph node involvement with any extent of primary cancer but no invasion of local structures, this is called stage IIB.
Stage III: Cancer invades through the muscular wall of the esophagus with lymph node spread and/or invasion of adjacent structures.
Stage IV: The cancer has spread to distant sites
Recurrent Cancer: The cancer has recurred after primary treatment.
The inherent inaccuracies of clinical staging have led to the use of other clinical categories of patients with cancer of the esophagus including:
Early or superficial cancer: Stage 0-I.
Localized Cancer: Stage 0-III.
Locally advanced cancer: Stage II and III.
Resectable cancer: Surgery was attempted and all visible cancer was removed.
Unresectable cancer: Surgery was attempted, but all visible cancer was not removed.
Inoperable cancer: Cancer was too widespread to attempt curative surgery.
Palliative surgery: Surgery was performed to relieve pain and/or difficulty swallowing, despite the fact that the cancer was too widespread to attempt curative surgery.
1 American Cancer Society. Cancer Facts & Figures 2012.
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