Esophageal cancer

Esophageal cancer is malignancy of the esophagus. There are various subtypes. Esophageal tumors usually lead to dysphagia (difficulty swallowing), pain and other symptoms, and is diagnosed with biopsy. Small and localized tumors are treated with surgery, and advanced tumors are treated with chemotherapy, radiotherapy or combinations. Prognosis depends on the extent of the disease and other medical problems, but is fairly poor.

Contents

1 Signs and symptoms

2 Cause and risk factors

3 Diagnosis

4 Staging

5 Treatment

5.1 General approaches
5.2 Tumor treatments

6 Follow-up and prognosis

7 Epidemiology

8 References

9 External Links

Signs and symptoms

Dysphagia (difficulty swallowing) is the first symptom in most patients. 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 poor nutrition and the active cancer. Pain, often of a burning nature, may be severe and worsened by swallowing, and can be spasmodic in character.

The presence of the tumor may disrupt normal peristalsis (the organised swallowing reflex), leading to nausea and vomiting, 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 superior vena caval obstruction (SVCO).

If the disease has spread to 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.

Cause and risk factors

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

Age and sex. Most patients are over 60, and it is more common in men.
Tobacco smoking and heavy alcohol use increase the risk, and together appear to increase the risk more than these two individually.
Swallowing lye or other caustic substances
Particular dietary substances, such as nitrosamine
A medical history of other head and neck cancers increases the chance of developing a second cancer in the head and neck area, including esophageal cancer.
Plummer-Vinson syndrome (anemia and esophageal webbing)
Tylosis and Howel-Evans syndrome (hereditary thickening of the skin of the palms and soles)
Gastroesophageal reflux disease (GERD) and its resultant Barrett's esophagus increase oesophageal cancer risk due to the chronic irritation of the mucosal lining (adenocarcinoma is more common in this condition), while all other risk factors predispose more for squamous cell carcinoma.

Risk appears to be less in patients using aspirin or related drugs (NSAIDs). Statistically, it appears that Helicobacter pylori, known for increasing risk for gastric cancer, actually decreases the risk of esophageal cancer (O'Connor 1999); the exact cause for this phenomenon is unclear.

Diagnosis

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 visualising the wall. Biopsies taken of suspicious lesions are then examined histologically for signs of malignancy.

Most tumors of the esophagus are malignant. A very small proportion (under 10%) is leiomyoma (smooth muscle tumor) or gastrointestinal stromal tumor (GIST). Malignant tumors are generally adenocarcinomas, squamous cell carcinomas, and occasionally small-cell carcinomas. The latter share many properties with small-cell lung cancer, and are relatively sensitive to chemotherapy compared to the other types.

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.

Staging

If biopsy suggests esophageal cancer, treatment is determined by the stage of the disease. This is determined by staging, and usually involves computed tomography (CT scan) of the chest and abdomen. If bone metastasis is suspected (e.g. pain or fracture), a bone scan may be performed, and bronchoscopy may be performed if the tumor is suspected to involve the trachea or bronchi.

The TNM classification is used to express the extent of the cancer:

Tumor extent: TX (can't be assessed), T0 (cannot be detected), Tis (carcinoma in situ), T1 (invades lamina propria or submucosa), T2 (invades muscularis propria), T3 (invades adventitia), T4 (invades adjacent structures)
Lymph node involvement: NX (can't be assessed), N0 (none), N1 (present)
Metastasis elsewhere: M0 (no metastasis) or M1 (distal metastasis present). M1a is used for localised metastasis in some situations, with M1b indicating metastasis outside this area.

The TNM information is sometimes aggregated into AJCC stages:

Stage 0: Tis, N0, M0 (non-invasive tumor)
Stage I: T1, N0, M0
Stage IIA: T2 or T3, N0, M0
Stage IIB: T1 or T2, N1, M0
Stage III: T3, N1, M0 or T4, Any N, M0
Stage IV: Any T, Any N, M1
Stage IVA: Any T, Any N, M1a
Stage IVB: Any T, Any N, M1b

Treatment

General approaches

The treatment is determined by the cellular type of cancer (adenocarcinoma, squamous cell carcinoma etc), 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, a stent may be inserted to keep the esophagus patent. 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.

Tumor treatments

Surgery is possible if the disease is localised (T1 or T2). If the tumor is larger but localised, chemotherapy and/or radiotherapy may occasionally shrink the tumor to the extent that it becomes "operable". Esophagectomy is the removal of a segment of the esophagus; as this shortens the distance between the throat and the stomach, the stomach is either placed in the chest cavity or a piece of small intestine is interposed.

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 (PDT), 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. Chemotherapy may be given after surgery (adjuvant, i.e. to reduce risk of recurrence), before surgery (neoadjuvant) or if surgery is not possible. 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.

Follow-up and prognosis

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

Prognosis of esophageal cancer is fairly poor. Five-year prognosis is about 6-16%. Options are limited when the cancer recurs, and emphasis is on symptom control and palliative care when it does.

Epidemiology

Esophageal cancer is a relatively rare form of cancer, but some world areas have a markedly higher incidence than others: China, India and Japan, as well as the United Kingdom, appear to have a higher incidence, as well as the region around the Caspian Sea (IARC 2003).

Annual incidence is between 3-11 per 100,000 for males and 0.6-6 per 100,000 for females (IARC 2003).

References

O'Connor HJ. Helicobacter pylori and gastro-oesophageal reflux disease-clinical implications and management. Aliment Pharmacol Ther 1999;13:117-27. PMID 10102940.
Stewart BW, Kleihues P (editors). World cancer report. Lyon: IARC, 2003. ISBN 9283204115.