Esophageal cancer

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Esophageal cancer
Classification & external resources

Endoscopic image of patient with esophageal adenocarcinoma seen at gastro-esophageal junction.
ICD-10	C15
ICD-9	150

Esophageal cancer is malignancy of the esophagus. There are various subtypes. Esophageal tumors usually lead to dysphagia (difficulty swallowing), pain and other symptoms, and are 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.^[1]

[edit] Signs and symptoms

Dysphagia (difficulty swallowing) is the first symptom in most patients. Odynophagia (painful swallowing) may 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 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. An early sign may be an unusually husky or raspy voice.

The presence of the tumor may disrupt normal peristalsis (the organised 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 superior vena cava syndrome. Fistulas may develop between the esophagus and the trachea, increasing the pneumonia risk; this symptom is usually heralded by cough, fever or aspiration.^[1]

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.

[edit] Cause and risk factors

[edit] 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.^[1] Some subtypes of cancer are linked to particular risk factors:

• Age. Most patients are over 60, and the median in US patients is 67.^[1]
• Gender. 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 or Parkia timoriana (found in southern Thailand diet).
• 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).
• Radiation therapy for other conditions in the mediastinum.^[1]
• Celiac disease and primary biliary cirrhosis predispose toward squamous cell carcinomas
• Gastroesophageal reflux disease (GERD) and its resultant Barrett's esophagus increase esophageal 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).^[2]
• According to one Italian study of "diet surveys completed by 5,500 Italians" — a study which has raised debates questioning its claims among cancer researchers cited in news reports about it — eating pizza more than once a week appears "to be a favorable indicator of risk for digestive tract neoplasms in this population."^[3]
• Recent epidemiologic studies have found that obesity (measured as BMI) is another strong risk factor for esophageal adenocarcinoma. ^[4]

[edit] Decreased risk

• Risk appears to be less in patients using aspirin or related drugs (NSAIDs).^[5]
• The role of Helicobacter pylori in progression to esophageal adenocarcinoma is still uncertain, but, on the basis of population data, it may carry a protective effect.^[6][7] It is postulated that H. pylori prevents chronic gastritis, which is a risk factor for reflux, which in turn is a risk factor for esophageal adenocarcinoma.^[8]
• According to the National Cancer Institute, "diets high in cruciferous (cabbage, broccoli, cauliflower) and green and yellow vegetables and fruits are associated with a decreased risk of esophageal cancer."^[9]
• Some scientific studies claim that various kinds of berries, particularly raspberries and black raspberries, have protective properties against cancer of the esophagus and other kinds of cancer.^[10]

[edit] Diagnosis

Endoscopy and radial endoscopic ultrasound images of submucosal tumour in mid-esophagus.

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.

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 CT scan is limited by its ability to detect masses (e.g. enlarged lymph nodes or involved organs) generally larger than 1cm. FDG-PET (positron emission tomography) scan is also being used to estimate whether enlarged masses are metabolically active, indicating faster-growing cells that might be expected in cancer. Esophageal endoscopic ultrasound (EUS) can provide staging information regarding the level of tumor invasion, and possible spread to regional lymph nodes.

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. Adenocarcinomas tend to occur distally and squamous cell carcinomas proximally, but the converse may also be the case.

[edit] Treatment

[edit] General approaches

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

Shows cancer blocking esophagus. Insets show enlarged area of cancer and a stent placed in the esophagus to keep it open.

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, a 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.

[edit] Tumor treatments

Surgery is possible if the disease is localised, which is the case in 20-30% of all patients. If the tumor is larger but localised, chemotherapy and/or radiotherapy may occasionally shrink the tumor to the extent that it becomes "operable"; however, this combination of treatments (referred to as neoadjuvant chemoradiation) is still somewhat controversial in most medical circles. Esophagectomy is the removal of a segment of the esophagus; as this shortens the distance between the throat and the stomach, some other segment of the digestive tract (typically the stomach or part of the colon) is placed in the chest cavity and interposed. If the tumor is metastatic, surgical resection is not considered worthwhile, but palliative surgery may offer some benefit.

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. In more recent studies, addition of epirubicin (ECF) was better than other comparable regimens in advanced nonresectable cancer.^[11] 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.

[edit] 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. Even in patients who undergo surgery with curative intent, the five year survival rate is only 25%, and prognosis is poorer in those who are not fit for surgery. Early emphasis on symptom control and palliative care may improve the quality of life.

[edit] 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.^[12]

Annual incidence is between 3-11 per 100,000 for males and 0.6-6 per 100,000 for females.^[12]

[edit] Incidence and Mortality

The American Cancer Society estimates that during 2007 approximately 15,560 new esophageal cancer cases will be diagnosed in the United States. In the U.S. an annual incidence of esophageal cancer of between 12,000 and 18,000 new cases. ^[13]

The esophageal cancer incidence and mortality rates for African Americans have been higher than the rate for Whites. ^[14] According to the NCI, incidence of adenocarcinoma of the esophagus, which is associated with Barrett's esophagus, is rising in the United States. This type is more common in Caucasian men over the age of 60.

Multiple reports indicate that esophageal adenocarcinoma incidence has increased during the past 20 yr, 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. ^[15]

Worldwide, the highest incidence of esophageal cancer is observed in Linxian, China, with an annual rate of more than 130 per 100,000 population. Other regions with high incidences of esophageal cancer include areas of Iran, Russia, Colombia, and South Africa. ^[4]

[edit] References

1. ^ ^{a b c d e} Enzinger PC, Mayer RJ. Esophageal cancer. N Engl J Med 2003;349:2241-52. PMID 14657432.
2. ^ Lagergren J, Bergstrom R, Lindgren A, Nyren O. Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. N Engl J Med 1999;340:825-31. PMID 10080844.
3. ^ Gallus S, Bosetti C, Negri E, Talamini R, Montella M, Conti E, Franceschi S, La Vecchia C. Does pizza protect against cancer? Int J Cancer 2003;107:283-4. PMID 12949808. Cited and qtd. by WebMD and BBC News.
4. ^ ^{a b} James C. Chou, MD & Frank G. Gress, MD. Esophageal Cancer Demographics & Epidemiology. Esophageal Cancer Overview (Cancer of the Esophagus). Retrieved on 2007-03-21.
5. ^ Corley DA, Kerlikowske K, Verma R, Buffler P. Protective association of aspirin/NSAIDs and esophageal cancer: a systematic review and meta-analysis. Gastroenterology 2003;124:47-56. PMID 12512029. See also NCI - "Esophageal Cancer (PDQ®): Prevention".
6. ^ Wong A, Fitzgerald RC. Epidemiologic risk factors for Barrett's esophagus and associated adenocarcinoma. Clin Gastroenterol Hepatol. 2005 Jan;3(1):1-10. PMID 15645398
7. ^ Ye W, Held M, Lagergren J, Engstrand L, Blot WJ, McLaughlin JK, Nyren O. Helicobacter pylori infection and gastric atrophy: risk of adenocarcinoma and squamous-cell carcinoma of the esophagus and adenocarcinoma of the gastric cardia. J Natl Cancer Inst. 2004 Mar 3;96(5):388-96. PMID 14996860
8. ^ Nakajima S, Hattori T. Oesophageal adenocarcinoma or gastric cancer with or without eradication of Helicobacter pylori infection in chronic atrophic gastritis patients: a hypothetical opinion from a systematic review. Aliment Pharmacol Ther. 2004 Jul;20 Suppl 1:54-61. PMID 15298606
9. ^ NCI Prevention: Dietary Factors, based on Chainani-Wu N. Diet and oral, pharyngeal, and esophageal cancer. Nutr Cancer 2002;44:104-26. PMID 12734057.
10. ^ See scientific studies cited by advocates of alternative natural foods cancer therapies, such as "Healing Fruits": Ellagic Acid" (Australia). For study conducted at the Comprehensive Cancer Center at the Ohio State University, see Abstract of article published by Tong Chen, Hyejeong Hwang, Miranda E. Rose, Ronald G. Nines, and Gary D. Stoner, "Epidemiology and Prevention: Chemopreventive Properties of Black Raspberries in N-Nitrosomethylbenzylamine-Induced Rat Esophageal Tumorigenesis: Down-regulation of Cyclooxygenase-2, Inducible Nitric Oxide Synthase, and c-Jun." Cancer Research 2006 Mar. 1; 66: 2853-59. Cf. online resources hosted by Oregon State University and sponsored by the Oregon berry industry; e.g., Berry Health Benefits Network and "How to Increase Your Health Vocabulary with Just One Bite" ("Natural Health Properties of Oregon Raspberries and Blackberries").
11. ^ Ross P, Nicolson M, Cunningham D, Valle J, Seymour M, Harper P, Price T, Anderson H, Iveson T, Hickish T, Lofts F, Norman A. Prospective randomized trial comparing mitomycin, cisplatin, and protracted venous-infusion fluorouracil (PVI 5-FU) with epirubicin, cisplatin, and PVI 5-FU in advanced esophagogastric cancer. J Clin Oncol 2002;20:1996-2004. PMID 11956258.
12. ^ ^{a b} Stewart BW, Kleihues P (editors). World cancer report. Lyon: IARC, 2003. ISBN 92-832-0411-5.
13. ^ What Are the Key Statistics About Cancer of the Esophagus?. Detailed Guide: Esophagus Cancer (Aug 2006). Retrieved on 2007-03-21.
14. ^ Incidence and Mortality Rate Trends. A Snapshot of Esophageal Cancer (Sep 2006). Retrieved on 2007-03-21.
15. ^ Kenneth J. Vega, M.D., M. Mazen JamaM.D.l (Sep 2000). Changing pattern of esophageal cancer incidence in New Mexico. Changing pattern of esophageal cancer incidence in New Mexico. Retrieved on 2007-03-21.

[edit] External links

• The Johns Hopkins Esophageal Cancer Web page
• Cathy's EC Cafe (Private support group resource)
• Esophageal Cancer Awareness Association
• "Learn More about Esophageal Cancer"
• MedlinePlus: Esophageal Cancer
• NCI Esophageal Cancer Home Page
• Oesophageal Cancer at Cancer Research UK
• Oesophageal Cancer Facts/ Resources (BBC) (Last updated: 30 Jan. 2004)
• Tea and Cancer Prevention Fact Sheet (NCI Fact Sheet)
• The UCLA Center for Esophageal Disorders