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

• Adenocarcinoma of Oesophagogastric Junction
• EGJ Adenocarcinoma
• Gastroesophageal Junction Adenocarcinoma

What is Adenocarcinoma of Esophagogastric Junction? (Definition/Background Information)

• Adenocarcinoma of Esophagogastric Junction (AEG) is a malignant tumor of the epithelium with glandular differentiation, typically affecting middle-aged and older adult males. A majority of the cancers of the esophagogastric junction are adenocarcinomas
• The esophagogastric junction (EGJ or gastroesophageal junction) is a short segment of the gastrointestinal tract that forms the junction of the esophagus (or food-pipe) and stomach. The EGJ is a muscular junction just below the diaphragm, at the mouth of the stomach/end of the esophagus
• Many researchers/medical professionals define the esophagogastric junction location in many terms, based on several different criteria/landmarks in the gastrointestinal tract. Thus, the exact diagnostic criteria, whether to term the cancer as esophageal, occurring at the esophagogastric junction, or gastric (stomach), may vary from one region to another
• Moreover, it is important to note that due to the presence of chronic gastroesophageal reflux disease (GERD) or other longstanding esophageal or stomach conditions, the mucosal/muscular surfaces of the end of the esophagus/the EGJ/the mouth of the stomach may be damaged, thus blurring the anatomic landmarks. Due to such damage in the esophagogastric junction area, the anatomical classification of where the cancer arises from, may also be difficult to determine
• However, from the point of view of treatment, it is not really important, whether the tumor arises from the lower esophagus, the EGJ, or from the proximal portion of stomach (nearer to the junction). Although, for pathologists and scientific researchers (and epidemiologists), an accurate determination of the site of origin of the tumor may be more important

Note: If even a small part of adenocarcinoma of esophagus crosses over to the esophagogastric junction, the cancer is called Adenocarcinoma of Esophagogastric Junction. But, if the entire cancer/tumor mass is above the esophagogastric junction, then it is called esophageal adenocarcinoma. And, if the tumor mass (malignancy) is entirely below the esophagogastric junction, then it is in the stomach and reportedly of gastric origin. In such cases, it is known as carcinoma of the proximal stomach.

• The incidence rate of Adenocarcinoma of Esophagogastric Junction is around the same as that of esophageal adenocarcinomas. The tumor type is observed at higher incidence rates among Caucasians (Europe and America)
• The primary risk factor for Adenocarcinoma of Esophagogastric Junction is Barrett esophagus, a condition that affects the lining of the esophageal wall. Other predisposing factors include obesity, chronic inflammation of the stomach, and smoking, to a lesser extent
• The cause of the condition is generally unknown, but the involvement of several genes and genetic abnormalities are noted. The tumor may arise from certain premalignant lesions (dysplasia) too
• 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, upper abdominal pain, and unintended loss of weight
• The treatment of choice 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, extent of tumor spread, and many other factors. In general, the prognosis of Adenocarcinoma of Esophagogastric Junction is difficult to predict

The following subtypes of Adenocarcinoma of Esophagogastric Junction are noted:

• Mucinous type of Adenocarcinoma of Esophagogastric Junction
• Tubular type of Adenocarcinoma of Esophagogastric Junction: This subtype is difficult to diagnose; it is often misdiagnosed as a premalignant lesion (dysplasia) or benign hyperplasia (enlargement of tissue due to cell proliferation)
• Papillary type of Adenocarcinoma of Esophagogastric Junction
• Signet-ring cell type of Adenocarcinoma of Esophagogastric Junction: It is not generally associated with chronic inflammation of the stomach (atrophic gastritis)
• Non signet-ring cell type of Adenocarcinoma of Esophagogastric Junction
• Mixed type of Adenocarcinoma of Esophagogastric Junction: In this type, histologically there may be different patterns noted when a tumor specimen is examined by a pathologist under the microscope

Who gets Adenocarcinoma of Esophagogastric Junction? (Age and Sex Distribution)

• Adenocarcinoma of Esophagogastric Junction 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 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 incidence of the cancer is seen to be increasing in well-developed countries (at 5% per year), such as USA, and many European nations

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

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

• Barrett esophagus: Intestinal metaplasia precursor lesions are seen in a majority of the individuals with this carcinoma type
  • Barrett esophagus 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)
  • Barrett esophagus showing frequent, chronic, and severe symptoms are at a greater risk for developing to Adenocarcinoma of EGJ. Chronic GERD is the most important risk factor for Barrett esophagus
• High BMI value (irrespective of GERD): Individuals, who are obese or those who are overweight, have an increased risk. Also, overweight and obese individuals have an increased risk for GERD and consequently Barrett esophagus
• Long-standing inflammation of the stomach leading to the thinning of the stomach lining (atrophic gastritis) may be a risk factor
• Smoking tobacco: Unlike esophageal adenocarcinoma where smoking is a significant risk factor, for Adenocarcinoma of Esophagogastric Junction, smoking is considered to be a ‘weak’ risk factor (lower risk)
• Diet: Lack of fresh vegetables and fruits, fish and fresh meat, dairy products; high consumption of processed meat (such as barbecued meat), may be risk factors for the condition
• Alcohol consumption: There is no clearly established risk observed
• Certain medications, such as H-2 receptor antagonists, calcium channel blockers, anti-asthmatics, and proton-pump inhibitors, may contribute to the risk

Note:

• Some reports indicate that the risk for Adenocarcinoma of Esophagogastric Junction may be lower, when individuals have intestinal metaplasia of stomach, than when compared to Barrett esophagus affecting the lower-third esophageal region
• Infection with Helicobacter pylori is not associated with increased risk for Adenocarcinoma of EGJ

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 Esophagogastric Junction? (Etiology)

The exact cause of development of Adenocarcinoma of Esophagogastric Junction is unknown.

• It is believed that the malignancy develops due to Barrett esophagus, or it can originate from the gastric region (stomach). The cancer shows an association with GERD in some cases
• Precursor lesions (intestinal metaplasia) are not always associated with Adenocarcinoma of Esophagogastric Junction. Some tumors are known to arise in the absence of such lesions
• Intestinal metaplasia occurring in the background of Barrett esophagus has a higher risk for developing adenocarcinoma, than short segment Barrett esophagus

Many genetic defects and gene involvement are noted, including loss or gains of chromosomal material.

• Over 40% of the tumors showed gains at the following chromosomal locations
  • 1q, 7q, 19q, and 20pq
  • 7p (with involvement of the EGFR gene)
  • 8q (with involvement of the MYC gene)
  • 17q (with involvement of the ERBB2 gene)
• In many cases, losses at the following chromosomal locations were noted
  • 3p, 4q, 5q31, and 9p
  • 5q21 (with involvement of APC gene and MCC gene)
  • 18q (with involvement of SMAD4 and DCC genes)
  • In males, Y chromosome 
• Also, in majority of tumors, genetic mutations involving the TP53 gene were noted
• Loss of heterozygosity (LOH) at 17p13 involving the TP53 gene was observed in about 46% of the cases

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 Esophagogastric Junction?

Adenocarcinoma of Esophagogastric Junction may present the following signs and symptoms:

• Normally, tumors in the initial stages are asymptomatic and do not present any significant symptoms
• Typical symptoms when the condition is severe, advanced, and/or presents as a bulky disease are:
  • Swallowing difficulties
  • Unexplained weight loss
  • Pain in the abdomen (epigastric pain)
• Chronic inflammation that leads to intestinal metaplasia affecting the esophagus or stomach is seen to occur prior to Esophagogastric Junction Adenocarcinoma
• Some individuals show a history of gastroesophageal reflux disease (GERD); while, some of peptic ulcer disease
• Large tumors may cause narrowing of esophagus
• Advanced tumors invade and may spread into the mucosal surfaces of the esophagus, to the stomach, to the mediastinal lymph nodes, or to the artery of stomach
• 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. They can ulcerate, bleed, and become painful
• Signs and symptoms of underlying gastroesophageal reflux disease and/or Barrett esophagus, if any present, may be noted

How is Adenocarcinoma of Esophagogastric Junction Diagnosed?

A diagnosis of Adenocarcinoma of Esophagogastric Junction 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 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

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:

• Adenocarcinoma of Esophagogastric Junction may be graded as well-differentiated, moderately-differentiated, or poorly-differentiated carcinomas. A majority of the tumors are believed to be poorly-differentiated tumors (high-grade)
• While examining the individual for Barrett esophagus on an endoscopy, the tumor is usually discovered during the early stages
• The staging criteria are based on where the epicenter of the tumor is located (whether it is nearer to the esophagus or to the stomach)
• Currently, no molecular markers for aiding in the treatment of the tumor have been found

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 Esophagogastric Junction?

The complications of Adenocarcinoma of Esophagogastric Junction 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 GI tract can lead to fistula formation, which can be life-threatening
• Stricture formation of the esophagogastric junction
• Lung infection leading to pneumonia
• The tumor can metastasize to the local/distant lymph nodes and to other organs
• 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
• Anastomotic leak; leakage of GI tract contents following surgical procedures, which can result in severe infection, sepsis, and even death

How is Adenocarcinoma of Esophagogastric Junction Treated?

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

• Any of the following surgical techniques may be employed based on the extent of the tumor and lymph node involvement:
  • Transthoracic en bloc esophagogastrectomy
  • Subtotal esophagectomy with resection of proximal stomach
  • Total gastrectomy with transhiatal resection of distal esophagus
  • Resection of the esophagogastric junction (limited)
• 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 Esophagogastric Junction be Prevented?

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

• Early diagnosis of Barrett esophagus is the best method to prevent it from progressing into cancer of the GI tract
• 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 is necessary.

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

• The prognosis of Adenocarcinoma of Esophagogastric Junction is generally guarded. It is described as being similar to esophageal adenocarcinoma (survival rates)
• 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
• In general, the prognosis of Adenocarcinoma of Esophagogastric Junction 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
  • Genetic abnormalities: When TP53 gene mutation was noted, studies showed poor prognosis from advanced disease. Also, mutations involving the COX2 gene has a poor prognosis
  • Histological subtype of the tumor
  • Involvement of the lymph nodes: Absence of lymph node metastasis is a favorable factor
  • 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 primary tumor can be removed completely): This is decidedly the most important prognostic factor
  • 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 and absence of post-operative complications: 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 Esophagogastric Junction:

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

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