What are the other Names for this Condition? (Also known as/Synonyms)

• Adenocarcinoma of Oesophagus
• Esophageal Adenocarcinoma
• Oesophageal Adenocarcinoma

What is Adenocarcinoma of Esophagus? (Definition/Background Information)

• Adenocarcinoma of Esophagus is a malignant tumor of the epithelium with glandular differentiation, typically affecting middle-aged and older adult males. The esophagus is a part of the upper gastrointestinal tract and is also known as the ‘food-pipe’
• The worldwide distribution of this form of esophageal cancer varies from areas of higher incidence (some European countries and Australia) to areas of very low incidence (many countries of Asia, Africa, and South America)
• The primary risk factor for Adenocarcinoma of Esophagus is Barrett esophagus, a condition that affects the lining of the esophageal wall. Other predisposing factors include smoking, dietary habits that exclude fresh fruits and vegetables, and obesity
• The cause of the condition is generally unknown, but many genetic abnormalities and gene involvement are noted. The tumor may arise from premalignant lesions
• Most tumors are diagnosed at a later stage (with involvement of lymph nodes and/or metastasis to other body sites). Superficial tumors may be painless and asymptomatic, while advanced cases present swallowing difficulties and chest and upper abdominal pain
• The treatment of choice for Esophageal Adenocarcinoma is a surgical excision with clear margins followed by radiation therapy/chemotherapy. In case of spread of cancer to other regions, a combination of treatments may be considered by the healthcare provider
• The prognosis depends upon a set of several factors including the surgical resectability, stage of the tumor, the extent of tumor spread, and many other factors. In general, the prognosis of Adenocarcinoma of Esophagus is difficult to predict

Who gets Adenocarcinoma of Esophagus? (Age and Sex Distribution)

• Adenocarcinoma of Esophagus constitute between 50-70% of esophageal carcinomas
• It is normally observed in adults over the age of 50 years (average age of 60 years). However, individuals of a wide age range may be affected (including children)
• Both males and females are affected, though the condition is much more common in males. The male-female ratio is between 4:1 and 7:1, varying from one geographical region to another
• All races and ethnic groups are at risk for the condition, but an elevated number of cases are noted among Caucasians and high-income groups
• The geographical distribution varies widely:
  • The cancer prevalence is about 10-50 cases per million populations in Europe and USA (more than squamous cell carcinoma of esophagus)
  • Higher prevalence rates are noted in some European nations, such as UK and Netherlands, Australia, and USA
  • The incidence is seen to be increasing in well-developed countries of Europe and in USA (at 5% per year)
  • Fewer cases are reported from Denmark, Norway, Sweden, and Eastern Europe. And, it is rare in the continents of South America, Africa, and Asia

Note: High risk areas are showing decline in esophageal cancer rates (typically SCC type), while low risk populations (Caucasians of US and north Europe) are showing an increase of the adenocarcinoma type.

What are the Risk Factors for Adenocarcinoma of Esophagus? (Predisposing Factors)

The risk factors for Adenocarcinoma of Esophagus include the following: (a combination of factors may be present in some individuals)

• Barrett esophagus:
  • It is a condition that results in the transformation of the normal esophageal lining (squamous epithelial lining) to the lining that is similar to the intestinal lining (columnar epithelial lining). Barrett esophagus is asymptomatic in 9 out of 10 individuals; and when present, it shows symptoms of gastroesophageal reflux disease (GERD)
  • 10% individuals with Barrett esophagus can develop Esophageal Adenocarcinoma. There is a 5-10 times greater chance for cancer, when the condition shows frequent, chronic, and severe symptoms
  • Barrett esophagus is of 2-types - short-segment (less than 2 cm length of the esophagus is involved) and long-segment (over 3 cm length involved). The short-segment type has a lower risk than the long-segment type for Esophageal Adenocarcinoma
• Barrett esophagus (intestinal metaplasia precursor lesions): Long-standing GERD injures the mucosal surface repeatedly, leading to intestinal metaplasia. Chronic GERD is the most important risk factor for Barrett esophagus and the risk is known to increase 30-60 times. Intestinal metaplasia (Barrett esophagus) is seen in most individuals with Esophageal Adenocarcinoma
• Smoking tobacco is a major risk factor: There is a 2-times higher risk for Esophageal Adenocarcinoma and it is reported that nearly 2 out of 5 cases of the cancer are in individuals who smoke. The risk of cancer may remain for nearly 30 years, even after one quits smoking
• High BMI value: Individuals who are obese have a 2.4 to 2.8 times increased risk; and, those who are overweight have an increased risk between 1.5 to 1.9 times. Also, overweight and obese individuals have an increased risk for GERD and Barrett esophagus
• Diet: Lack of fresh vegetables and fruits, fish and fresh meat, dairy products, etc.; also, a high consumption of processed meat (such as barbecued meat)
• Nutritional deficiencies that include vitamins A, B1, B2, B6, and C, and minerals zinc and molybdenum
• Radiation therapy for breast cancer

Note:

• Alcohol consumption: There is no clearly established risk observed for adenocarcinoma, although studies have shown an increased risk for squamous cell carcinoma
• Some medications, such as H-2 receptor antagonists, calcium channel blockers, anti-asthmatics, and proton-pump inhibitors, are believed to increase the risk. However, various study reports indicate that it is the conditions the drugs are used to treat that increase the risk for Esophageal Adenocarcinoma

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Adenocarcinoma of Esophagus? (Etiology)

The exact cause of development of Adenocarcinoma of Esophagus is unknown. Some genetic defects and gene involvement are noted.

• Scientists believe that the fact that Barrett esophagus is predominantly noted in Caucasians, who are affected at an younger age, seems to point to the involvement of certain genetic factors
• Studies have indicated that some individuals show a clustering within families of the following conditions (indicating a genetic involvement):
  • Barrett esophagus
  • Gastroesophageal reflux disease (GERD)
  • Adenocarcinoma of Esophagus
• Genetic polymorphism: The involved genes include GSTP1 gene mutations when Barrett esophagus is seen (many other genetic and chromosomal alterations have been noted too)
• GSTM1 and GSTT1 gene mutations are associated with individuals in whom smoking as a risk factor
• Premalignant lesions, called dysplasia, are believed to be the point of origin for Esophageal Adenocarcinoma in a majority of cases. The greater the area involved, the higher is the risk for cancer. Dysplastic lesions are reported to show involvement of TP53 gene mutation

In general, it is known that cancers form when normal, healthy cells begin transforming into abnormal cells - these cancer cells grow and divide uncontrollably (and lose their ability to die), resulting in the formation of a mass or a tumor.

• Many cancer types are caused by genetic mutations. These can occur, due to inherited mutations, or mutations that occur due to environmental factors 
• The transformation of normally healthy cells into cancerous cells may be the result of genetic mutations. Mutations allow the cancer cells to grow and multiply uncontrollably to form new cancer cells
• These tumors can invade nearby tissues and adjoining body organs, and even metastasize and spread to other regions of the body

What are the Signs and Symptoms of Adenocarcinoma of Esophagus?

Adenocarcinoma of Esophagus may present the following signs and symptoms:

• When only the mucosal or submucosal surfaces are involved, it is known as a superficial tumor. Initial-stage superficial tumors may be asymptomatic
• Site of the tumor:
  • Mostly observed in the site of precancerous lesions; many are located in the distal esophagus (nearer to the esophagogastric junction and stomach)
  • Some cases are seen in the proximal region (middle-third region of esophagus)
  • Most arise in the lower-third portion of the esophagus (from the Barrett mucosa); rare case are seen in the upper-third portion of the esophagus
  • In the absence of Barrett esophagus, tumors are rarely noted in the upper/middle third portion of esophagus
• The dysplasia site may be irregular, flat, ulcerated/eroded, nodular, or even indistinguishable
• Tumors may be polypoid and cause narrowing of esophagus
• Commonly observed symptoms for advanced cancer are swallowing difficulties, chest pain (retrosternal pain), upper abdominal pain (epigastric pain), narrowing of esophagus that can cause regurgitation or vomiting sensation
• Advanced tumors invade into the esophageal wall beyond the submucosal surface. Early stage is stage 0, when only the mucosal surfaces are involved (and may be the submucosal surfaces too)
• Esophageal carcinomas spread up and down the food-pipe or around the GI tube. The spread during later stages occurs along the surface (expansively) or deeper into the tissue layers (infiltrative)
• Large tumors may cause a pressure effect by compressing adjoining structures and organs
• Large tumors may ulcerate and bleed and become painful
• Involvement of lymph nodes: Local spread and deep penetration leads to a greater chance of lymph node involvement. When the cancer is seen along-with Barrett esophagus, the spread is to lymph nodes of the mediastinal (chest), heart, and stomach region
• Signs and symptoms of underlying gastroesophageal reflux disease and/or Barrett esophagus may be noted

At diagnosis, most Adenocarcinomas of Esophagus are at advanced stages with deep penetration into the GI wall layers. Many tumors are flat and ulcerated; 35% of the tumors are polypoid in shape or fungating type.

How is Adenocarcinoma of Esophagus Diagnosed?

A diagnosis of Adenocarcinoma of Esophagus may involve the following:

• A thorough medical history and physical examination
• X-ray of the chest
• CT or MRI scan of the chest: For advanced cases and to check cancer growth and spread, including lymph node involvement
• Upper GI endoscopy: An endoscopic procedure is performed using an instrument called an endoscope, which consists of a thin tube and a camera. Using this technique, the radiologist can have a thorough examination of the insides of the upper gastrointestinal tract
• Endoscopic ultrasonography: During this procedure, fine needle aspiration biopsy (FNAB) can be performed on the affected area. This is a good technique for tumor detection, including tumor invasion parameters, and whether nearby lymph nodes are affected (tumor staging)
• Endocytoscopy: It is a non-invasive technique helpful for invasive carcinomas that are located superficially
• Early cancer lesions may be detected using narrow band imaging technique
• Barium swallow
• Whole body PET scans to determine how far the cancer has spread to other organ systems
• When Adenocarcinoma of Esophagus is observed superficially, it may be diagnosed following procedures for Barrett esophagus or GERD, based on symptom presentation

Note: Adenocarcinoma in situ and superficially-invasive Adenocarcinoma of Esophagus does not cause significant symptoms. Such tumors are diagnosed either during an endoscopy for GERD or during follow-up endoscopies for previously diagnosed Barrett esophagus (as part of surveillance process).

Although the above modalities can be used to make an initial diagnosis, a tissue biopsy of the tumor is necessary to make a definitive diagnosis to begin treatment. The tissue for diagnosis can be procured in multiple different ways which include: 

• Fine needle aspiration (FNA) biopsy of the tumor: A FNA biopsy may not be helpful, because one may not be able to visualize the different morphological areas of the tumor and the tumor may be misdiagnosed. Hence, a FNA biopsy as a diagnostic tool has certain limitations, and an open surgical biopsy is preferred
• Core biopsy of the tumor 
• Open biopsy of the tumor

Tissue biopsy:

• A tissue biopsy of the tumor is performed and sent to a laboratory for a pathological examination. A pathologist examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis. Examination of the biopsy under a microscope by a pathologist is considered to be gold standard in arriving at a conclusive diagnosis
• Biopsy specimens are studied initially using Hematoxylin and Eosin staining. The pathologist then decides on additional studies depending on the clinical situation
• Sometimes, the pathologist may perform special studies, which may include immunohistochemical stains, molecular testing, and very rarely, electron microscopic studies to assist in the diagnosis

Note:

• Esophageal carcinomas may be graded as well-differentiated, moderately-differentiated, poorly-differentiated, or undifferentiated carcinomas. The use of tumor grading in predicting prognosis is unclear and controversial
• Most Esophageal Adenocarcinomas are well- to moderately- differentiated, while some are poorly-differentiated or undifferentiated
• Esophageal biopsies with intestinal metaplasia may show no dysplasia, a low-grade dysplasia, or a high-grade dysplasia. Such findings help in establishing subsequent endoscopy surveillance procedures

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Adenocarcinoma of Esophagus?

The complications of Adenocarcinoma of Esophagus may include the following:

• Ulceration of the tumor can lead to secondary infections of bacteria and fungus
• Compression of the underlying nerve, which can affect nerve function
• Severe obstruction of the food-pipe with pain, leading to difficulties in eating. This can lead to extreme weight loss due to malnutrition
• Perforation or rupture of the esophagus can lead to the formation of tracheoesophageal fistula, which in turn can cause aspiration pneumonia. This is a life-threatening condition
• Stricture formation of esophagus
• Vocal cord paralysis
• Lung infection leading to pneumonia
• The tumor can metastasize to the local and distant lymph nodes
• When metastasis occurs, the sites involved are the stomach, lungs, bronchus, trachea, pleura, aorta, pericardium, heart, and the central nervous system
• Recurrence of the tumor is frequent following treatment
• Side effects of chemotherapy (such as toxicity) and radiation
• Damage to the muscles, vital nerves, and blood vessels, during surgery
• Post-surgical infection at the wound site is a potential complication

How is Adenocarcinoma of Esophagus Treated?

Surgery is very important for treating Adenocarcinoma of Esophagus for both the initial and later stage tumors. The treatment may also include a combination of radiation therapy and chemotherapy.

• When the tumor is confined to the esophageal surface, then endoscopic mucosal/submucosal resection (or surgical removal via endoscopy) is undertaken
• Esophagectomy or surgery to remove part (or all) of esophagus
• If the tumor has metastasized, then a combination of chemotherapy, radiation therapy, and invasive procedures may be used to treat the tumor
• Palliative care is provided for advanced cancer stages
• Follow-up care with regular screening and check-ups are very important and encouraged

Clinical trials: In advanced stages of cancer progression, there may be some newer treatment options currently on clinical trials, which can be considered for some patients depending on their respective risk factors.

How can Adenocarcinoma of Esophagus be Prevented?

Currently, there are no known methods to prevent Esophageal Adenocarcinoma occurrence. However, the risk for the condition may be lowered through the following considerations:

• Early diagnosis of Barrett esophagus is the best way to prevent it from progressing into esophageal cancer
• Treatment of GERD to reduce damage to the esophagus
• Bringing about certain lifestyle changes such as diet adjustments to reduce fatty food and caffeine intake, reduction of alcohol intake, and cessation of smoking
• Consuming a diet that is rich in whole grains, vegetables, and fruits
• Correcting any nutritional imbalances through adequate vitamin and mineral supplementation
• Taking foods rich in vitamin D and calcium
• Physical activities and regular exercising
• In order to avoid a relapse or be prepared for a recurrence, the entire diagnosis, treatment process, drugs administered, etc. should be well-documented and follow-up measures initiated

Regular medical screening at periodic intervals with blood tests, scans, and physical examinations, are mandatory, due to its metastasizing potential and possibility of recurrence. Often several years of active vigilance are necessary.

What is the Prognosis of Adenocarcinoma of Esophagus? (Outcomes/Resolutions)

• The prognosis of Adenocarcinoma of Esophagus is generally guarded. The 5-year survival rate is 41%, if the tumor is confined to the esophagus; 23%, when the local tissues, organs, and lymph nodes are involved; and 5%, if distant metastasis with involvement of organs away from the tumor site is noted
  • The surgical options (including capability of complete surgical resection) can sway prognosis favorably. If a complete regression of the tumor is noted, no lymph nodes are affected, and no metastasis is seen, then the prognosis is reportedly good
  • On the other hand, if surgery is not possible, then the prognosis is poor (the individual may survive for less than 5 years)
  • The prognosis also depends on the depth of tumor invasion
  • Genetic defects involving TP53, COX2, MMP1 genes, or ERBB2/HER2-neu amplification are negative prognostic indicators
• The prognosis of Adenocarcinoma of Esophagus depends upon a set of several factors, which include: 
  • Stage of tumor: With lower-stage tumors, when the tumor is confined to site of origin, the prognosis is usually excellent with appropriate therapy. In higher-stage tumors, such as tumors with metastasis, the prognosis is poor
  • Overall health of the individual: Individuals with overall excellent health have better prognosis compared with those with poor health
  • Age of the individual: Older individuals generally have poorer prognosis than younger individuals
  • The size of the tumor: Individuals with small-sized tumors fare better than those with large-sized tumors
  • Individuals with bulky disease may have a poorer prognosis
  • Involvement of vital organs may complicate the condition
  • The surgical resectability of the tumor (meaning, if the tumor can be removed completely)
  • Whether the tumor is occurring for the first time, or is a recurrent tumor. Recurring tumors have worse prognosis compared to tumors that do not recur 
  • Response to treatment: Tumors that respond to treatment have better prognosis compared to tumors that do not respond to treatment
  • Progression of the condition makes the outcome worse
• An early diagnosis and prompt treatment of the tumor generally yields better outcomes than a late diagnosis and delayed treatment
• The combination chemotherapy drugs used, may have some severe side effects (such as cardio-toxicity). This chiefly impacts the elderly adults, or those who are already affected by other medical conditions. Tolerance to the chemotherapy sessions is a positive influencing factor

Additional and Relevant Useful Information for Adenocarcinoma of Esophagus:

The following DoveMed website links are useful resources for additional information:

http://www.dovemed.com/diseases-conditions/cancer/