Esophageal cancer

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Esophageal cancer
Classification and external resources

Endoscopic image of patient with esophageal adenocarcinoma seen at gastro-esophageal junction.
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Esophageal cancer
Classification and external resources

Endoscopic image of patient with esophageal adenocarcinoma seen at gastro-esophageal junction.
eMedicinearticle/277930 article/368206

Esophageal cancer (or oesophageal cancer) is malignancy of the esophagus. There are various subtypes, primarily squamous cell cancer (approx 90-95% of all esophageal cancer worldwide) and adenocarcinoma (approx. 50-80% of all esophageal cancer in the United States). Squamous cell cancer arises from the cells that line the upper part of the esophagus. Adenocarcinoma arises from glandular cells that are present at the junction of the esophagus and stomach.[1]

Esophageal tumors usually lead to dysphagia (difficulty swallowing), pain and other symptoms, and are diagnosed with biopsy. Small and localized tumors are treated surgically with curative intent. Larger tumors tend not to be operable and hence are treated with palliative care; their growth can still be delayed with chemotherapy, radiotherapy or a combination of the two. In some cases chemo- and radiotherapy can render these larger tumors operable. Prognosis depends on the extent of the disease and other medical problems, but is generally fairly poor.[2]



Micrograph of an esophageal adenocarcinoma (dark blue - upper-left of image) and normal squamous epithelium (upper-right of image). H&E stain.

Esophageal cancers are typically carcinomas which arise from the epithelium, or surface lining, of the esophagus. Most esophageal cancers fall into one of two classes: squamous cell carcinomas, which are similar to head and neck cancer in their appearance and association with tobacco and alcohol consumption, and adenocarcinomas, which are often associated with a history of gastroesophageal reflux disease and Barrett's esophagus. A general rule of thumb is that a cancer in the upper two-thirds is a squamous cell carcinoma and one in the lower one-third is an adenocarcinoma. Rare histologic types of esophageal cancer are different variants of the squamous cell carcinoma, and non-epithelial tumors, such as leiomyosarcoma, malignant melanoma, rhabdomyosarcoma, lymphoma and others.[3][4]

Signs and symptoms

Dysphagia (difficulty swallowing) and odynophagia (painful swallowing) are the most common symptoms of esophageal cancer. Dysphagia is the first symptom in most patients. Odynophagia may also be present. Fluids and soft foods are usually tolerated, while hard or bulky substances (such as bread or meat) cause much more difficulty. Substantial weight loss is characteristic as a result of reduced appetite, poor nutrition and the active cancer. Pain behind the sternum or in the epigastrium, often of a burning, heartburn-like nature, may be severe, present itself almost daily, and is worsened by swallowing any form of food. Another sign may be an unusually husky, raspy, or hoarse-sounding cough, a result of the tumor affecting the recurrent laryngeal nerve.

The presence of the tumor may disrupt normal peristalsis (the organized swallowing reflex), leading to nausea and vomiting, regurgitation of food, coughing and an increased risk of aspiration pneumonia. The tumor surface may be fragile and bleed, causing hematemesis (vomiting up blood). Compression of local structures occurs in advanced disease, leading to such problems as upper airway obstruction and superior vena cava syndrome. Fistulas may develop between the esophagus and the trachea, increasing the pneumonia risk; this condition is usually heralded by cough, fever or aspiration.[2]

Most of the people diagnosed with esophageal cancer have late-stage disease, because people usually do not have significant symptoms until half of the inside of the esophagus, called the lumen, is obstructed, by which point the tumor is fairly large. [5]

If the disease has spread elsewhere, this may lead to symptoms related to this: liver metastasis could cause jaundice and ascites, lung metastasis could cause shortness of breath, pleural effusions, etc.


Increased risk

Barrett's esophagus is considered to be a risk factor for esophageal adenocarcinoma.

There are a number of risk factors for esophageal cancer.[2] Some subtypes of cancer are linked to particular risk factors:

Decreased risk


Endoscopy and radial endoscopic ultrasound images of submucosal tumor in mid-esophagus.
Cancer of the esophagus, CT with contrast, axial image.
Esophageal cancer, CT scan with contrast, coronal image.

Clinical evaluation

Although an occlusive tumor may be suspected on a barium swallow or barium meal, the diagnosis is best made with esophagogastroduodenoscopy (EGD, endoscopy); this involves the passing of a flexible tube down the esophagus and examining the wall. Biopsies taken of suspicious lesions are then examined histologically for signs of malignancy.

Additional testing is usually performed to estimate the tumor stage. Computed tomography (CT) of the chest, abdomen and pelvis can evaluate whether the cancer has spread to adjacent tissues or distant organs (especially liver and lymph nodes). The sensitivity of a CT scan is limited by its ability to detect masses (e.g. enlarged lymph nodes or involved organs) generally larger than 1 cm. Positron emission tomography is also used to estimate the extent of the disease and is regarded more precise than CT alone. Esophageal endoscopic ultrasound can provide staging information regarding the level of tumor invasion, and possible spread to regional lymph nodes.

The location of the tumor is generally measured by the distance from the teeth. The esophagus (25 cm or 10 inches long) is commonly divided into three parts for purposes of determining the location. Adenocarcinomas tend to occur distally and squamous cell carcinomas proximally, but the converse may also be the case.


Self-expandable metallic stents are used for the palliation of esophageal cancer.

General approaches

Esophageal cancer affecting the lower esophageus. Insets show the tumor in more detail both before and after placement of a stent.

The treatment is determined by the cellular type of cancer (adenocarcinoma or squamous cell carcinoma vs other types), the stage of the disease, the general condition of the patient and other diseases present. On the whole, adequate nutrition needs to be assured, and adequate dental care is vital.

If the patient cannot swallow at all, an esophageal stent may be inserted to keep the esophagus patent; stents may also assist in occluding fistulas. A nasogastric tube may be necessary to continue feeding while treatment for the tumor is given, and some patients require a gastrostomy (feeding hole in the skin that gives direct access to the stomach). The latter two are especially important if the patient tends to aspirate food or saliva into the airways, predisposing for aspiration pneumonia.

Esophagectomy is the removal of a segment of the esophagus; as this shortens the length of the remaining esophagus, some other segment of the digestive tract (typically the stomach or part of the colon or jejunum) is pulled up to the chest cavity and interposed.[22] If the tumor is unresectable or the patient is not fit for surgery, palliative esophageal stenting can allow the patient to tolerate soft diet.

Types of esophagectomy:

Data are accumulating to indicate endoscopic therapy is a safe, less invasive, and effective therapy for very early esophageal cancer. The candidates for endoscopic therapy are Stage 1 patients with tumors invading into the lamina propria (T1 mucosal) or submucosa (T1 submucosal) that do not have regional or distant metastasis. Patients with carcinoma in situ or high-grade dysplasia can also be treated with endoscopic therapy. Submucosal cancers with increased risk of nodal metastases may not be as amenable to curative therapy.

Forms of endoscopic therapy have been used for Stage 0 and I disease: endoscopic mucosal resection (EMR) and mucosal ablation using radiofrequency ablation, photodynamic therapy, Nd-YAG laser, or argon plasma coagulation.

EMR has been advocated for early cancers (that is, those that are superficial and confined to the mucosa only) and has been shown to be a less invasive, safe, and highly effective nonsurgical therapy for early squamous cell esophageal cancer. It has also been shown to have be safe and effective for early adenocarcinoma arising in Barrett’s esophagus. The prognosis after treatment with EMR is comparable to surgical resection. This technique can be attempted in patients, without evidence of nodal or distant metastases, with differentiated tumors that are slightly raised and less than 2 cm in diameter, or in differentiated tumors that are ulcerated and less than 1 cm in diameter. The most commonly employed modalities of EMR include strip biopsy, double-snare polypectomy, resection with combined use of highly concentrated saline and epinephrine, and resection using a cap.

The strip biopsy method for endoscopic mucosal resection of esophageal cancer is performed with a double-channel endoscope equipped with grasping forceps and snare. After marking the lesion border with an electric coagulator, saline is injected into the submucosa below the lesion to separate the lesion from the muscle layer and to force its protrusion. The grasping forceps are passed through the snare loop. The mucosa surrounding the lesion is grasped, lifted, and strangulated and resected by electrocautery. The endoscopic double-snare polypectomy method is indicated for protruding lesions. Using a double-channel scope, the lesion is grasped and lifted by the first snare and strangulated with the second snare for complete resection.

Endoscopic resection with injection of concentrated saline and epinephrine is carried out using a double-channel scope. The lesion borders are marked with a coagulator. Highly concentrated saline and epinephrine are injected (15–20 ml) into the submucosal layer to swell the area containing the lesion and elucidate the markings. The mucosa outside the demarcated border is excised using a high-frequency scalpel to the depth of the submucosal layer. The resected mucosa is lifted and grasped with forceps, trapping and strangulating the lesion with a snare, and then resected by electrocautery.

Another method of EMR employs the use of a clear cap and prelooped snare inside the cap. After insertion, the cap is placed on the lesion and the mucosa containing the lesion is drawn up inside the cap by aspiration. The mucosa is caught by the snare and strangulated, and finally resected by electrocautery. This is called the "band and snare" or "suck and cut" technique. The resected specimen is retrieved and submitted for microscopic examination for determination of tumor invasion depth, resection margin, and possible vascular involvement. The resulting "ulcer" heals within three weeks.

EMR can also be used to debulk or completely treat polypoid dysplastic or malignant lesions in Barrett’s esophagus, the known precursor lesion to esophageal adenocarcinoma. In a preliminary report from Germany, EMR was performed as primary treatment or adjunctive therapy following photodynamic therapy for early adenocarcinomas in Barrett's esophagus. The "suck and cut" technique (with and without prior saline injection) was used, as well as the "band and cut" technique. Although all tumors were resected without difficulty, 12.5% developed bleeding (which was managed successfully by endoscopic therapy). Eighty-one percent of the lesions were completely resected. The other lesions were also treated with other endoscopic techniques.

The major complications of endoscopic mucosal resection include postoperative bleeding, perforation and stricture formation. During the procedure, an injection of 100,000 times diluted epinephrine into the muscular wall, along with high-frequency coagulation or clipping can be applied to the bleeding point for hemostasis. It is important to administer acid-reducing medications to prevent postoperative hemorrhage. Perforation may be prevented with sufficient saline injection to raise the mucosa containing the lesion. The "non-lifting sign" and complaints of pain when the snare strangulates the lesion are contrainidications of EMR. When perforation is recognized immediately after a procedure, the perforation should be closed by clips. Surgery should be considered in cases of endoscopic closure failure. The incidence of complications ranges from 0–50% and squamous cell recurrence rates range from 0–8%.

Laser therapy is the use of high-intensity light to destroy tumor cells; it affects only the treated area. This is typically done if the cancer cannot be removed by surgery. The relief of a blockage can help to reduce dysphagia and pain. Photodynamic therapy, a type of laser therapy, involves the use of drugs that are absorbed by cancer cells; when exposed to a special light, the drugs become active and destroy the cancer cells.

Chemotherapy depends on the tumor type, but tends to be cisplatin-based (or carboplatin or oxaliplatin) every three weeks with fluorouracil (5-FU) either continuously or every three weeks. In more recent studies, addition of epirubicin was better than other comparable regimens in advanced nonresectable cancer.[23] Chemotherapy may be given after surgery (adjuvant, i.e. to reduce risk of recurrence), before surgery (neoadjuvant) or if surgery is not possible; in this case, cisplatin and 5-FU are used. Ongoing trials compare various combinations of chemotherapy; the phase II/III REAL-2 trial – for example – compares four regimens containing epirubicin and either cisplatin or oxaliplatin, and either continuously infused fluorouracil or capecitabine.

Radiotherapy is given before, during or after chemotherapy or surgery, and sometimes on its own to control symptoms. In patients with localised disease but contraindications to surgery, "radical radiotherapy" may be used with curative intent.

Radiofrequency ablation is a new treatment modality for the treatment of Barrett's esophagus and dysplasia, and has been the subject of numerous published clinical trials. The findings demonstrate radiofrequency ablation has an efficacy of 80-90% or greater with respect to complete clearance of Barrett's esophagus and dysplasia with durability up to 5 years and a favorable safety profile.[24] [25] [26] [27] Recent clinical trials have shown that endoscopic resection of esophageal mucosal irregularities and nodules which contain dysplasia or carcinoma combined with subsequent radiofrequency ablation of the remaining flat Barrett's esophagus and dysplasia can effectively and safely eradicate the disease.[28] Further, a recent multicenter randomized control trial found that in patients with Barrett's esophagus containing nodules or mucosal irregularities which contained high grade dysplasia or cancer, subsequent radiofrequency ablation resulted not only in eradication of Barrett's esophagus and dysplasia, but had significantly less esophageal stricture versus patients who had circumferential endoscopic mucosal resection for their disease. [29]


Patients are followed up frequently after a treatment regimen has been completed. Frequently, other treatments are necessary to improve symptoms and maximize nutrition.


In general, the prognosis of esophageal cancer is quite poor, because most patients present with advanced disease. By the time the first symptoms such as dysphagia start manifesting themselves, the cancer has already well progressed. The overall five-year survival rate (5YSR) is approximately 15%, with most patients dying within the first year of diagnosis.[30]

Individualized prognosis depends largely on stage. Those with cancer restricted entirely to the esophageal mucosa have about an 80% 5YSR, but submucosal involvement brings this down to less than 50%. Extension into the muscularis propria (muscular layer of the esophageus) has meant a 20% 5YSR and extension to the structures adjacent to the esophagus results in a 7% 5YSR. Patients with distant metastases (who are not candidates for curative surgery) have a less than 3% 5YSR. .


Age-standardized death from esophagus cancer per 100,000 inhabitants in 2004[31]
  no data
  less than 3
  more than 35

Esophageal cancer is a relatively rare form of cancer, but some world areas have a markedly higher incidence than others: Belgium, China, Iran, Iceland, India, Japan, the United Kingdom appear to have a higher incidence, as well as the region around the Caspian Sea.[32] The American Cancer Society estimated that during 2007, approximately 15,560 new esophageal cancer cases will be diagnosed in the United States.[33]

In the United States, squamous cell carcinoma of the esophagus usually affects African American males with a history of heavy smoking or alcohol use. Until the 1970s, squamous cell carcinoma made up the vast majority of esophageal cancers in the United States. In recent decades, incidence of adenocarcinoma of the esophagus (which is associated with Barrett's esophagus) steadily rose in the United States to the point that it has now surpassed squamous cell carcinoma in this country. In contrast to squamous cell carcinoma, esophageal adenocarcinoma is more common in Caucasian men (over the age of 60) than it is in African Americans. Multiple reports indicate esophageal adenocarcinoma incidence has increased during the past 20 years, especially in non-Hispanic white men. Esophageal adenocarcinoma age-adjusted incidence increased in New Mexico from 1973 to 1997. This increase was found in non-Hispanic whites and Hispanics and became predominant in non-Hispanic whites.[34] Esophageal cancer incidence and mortality rates for African Americans continue to be higher than the rate for Causasians. However, incidence and mortality of esophageal cancer has significantly decreased among African Americans since the early 1980s, whereas with Caucasians, it has slightly increased.[35]


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