Esophageal cancer is a malignant proliferation of esophageal cells. The most common types of esophageal cancers are squamous cell carcinoma and adenocarcinoma. It occurs as a result of uncontrolled growth and division of the mutated esophageal cells.

Risk factors for the development of esophageal cancer include Barrett’s esophagus, male gender, obesity, smoking, and alcohol consumption. Symptoms of esophageal cancer usually appear only when the cancer has reached an advanced stage. Patients usually complain of dysphagia (difficulty swallowing) which usually becomes worse over time. Other symptoms may include unintentional weight loss, heartburn, chronic cough, pneumonia and odynophagia (painful swallowing).

Multiple methods are used to diagnose esophageal cancer, including taking a patient’s medical history and performing a physical exam, imaging tests such as a CT scan, endoscopic procedures such as an upper gastrointestinal (GI) endoscopy and laboratory tests such as a complete blood count (CBC).

Treatment options for esophageal cancer vary depending on the stage and type of the cancer, the location of the tumor and the patient’s overall health. Treatment options are surgical (esophagectomy), radiation therapy, chemotherapy drugs taken either orally or intravenously, targeted therapy and endoscopic treatments.

Complications of esophageal cancer are generally a consequence of the treatment. Complications of radiotherapy and chemotherapy include fatigue (tiredness), nausea and vomiting. Complications of surgical options usually include leaks, voice changes, delayed emptying of the stomach and acid reflux.

The risk of developing esophageal cancer may be decreased by making lifestyle changes such as avoiding smoking and alcohol consumption, maintaining a healthy weight. Getting treatment for Barrett’s esophagus may also reduce the risk of developing esophageal cancer.

The prognosis of esophageal cancer depends on factors like the stage the cancer was detected. The overall 5-year survival rate in patients ranges from 5% to 30%. Esophageal cancer is the eighth most common cancer worldwide and is the sixth highest cause of cancer mortality.  According to the World Cancer Research Fund International, 456,000 new cases of esophageal cancer were diagnosed in 2012, accounting for 3.2% of all cancers  .

It is a malignant proliferation of esophageal cells that begins from inside the esophageal lumen (inner layer of cells), growing towards the outside.

The most common types of malignant esophageal tumors include squamous cell carcinoma and adenocarcinoma.

Squamous cell carcinoma

These cancers start in the squamous cells that comprise the inner lining of the esophagus. These cancers may occur anywhere along the esophagus but tend to develop in the upper and middle part. 

Adenocarcinoma

These cancers arise from the gland cells that produce mucus in the esophageal lining. These cancers mostly begin in the lower part of the esophagus and are the most common type of esophageal cancer. 

Rare malignancies affecting the esophagus include spindle cell carcinoma, lymphomas, melanomas, and sarcomas. 

No exact cause for esophageal cancer exists. Esophageal cancer happens when esophageal cells develop mutations (errors) in their DNA. The errors cause uncontrolled growth and division of the mutated cells. The accumulating mutated cells create a tumor in the esophagus that may metastasize to other parts of the body.

Risk factors for esophageal cancer development include: 

• Barrett’s esophagus (precancerous changes in the esophagus).
• Old age.
• Achalasia (an uncommon swallowing disorder).
• Smoking and/ or alcohol consumption. Together they have a synergistic effect where together they cause a significantly increased risk compared to than using either alone.
• Drinking very hot liquids regularly (temperatures of 65° C).
• Chemical injury to the esophagus by the accidental consumption of lye, a chemical found in household cleaners such as drain cleaners. .
• Some esophageal infections.
• Tylosis palmaris (a genetic disorder).
• Gastroesophageal reflux disease (GERD).
• Obesity.
• Having bile reflux.
• Undertaking radiation treatment to the chest or upper abdomen.
• Plummer-Vinson syndrome (a rare condition that causes swallowing problems ).
• Betel quid (a leaf that is chewed in some parts of the world, particularly east Asia).
• Family history of esophageal cancer.
• Males are three times more likely to develop esophageal cancer than female.
• History of certain other cancers such as lung, mouth and throat cancer.
• Human papilloma virus (HPV) infection.
• A Diet poor in fruits and vegetables.
• Exposure to dry cleaning chemicals.
• Eating red and processed meat.
• Gene mutations.
• Cystic fibrosis.
• Exposure to chemical fumes in the workplace such as solvents used for dry cleaning.

Repetitive exposure of the esophageal cells to irritative substances which damage the DNA in these cells may lead to uncontrolled proliferation of the cells by activation of the oncogene and repression of the tumor suppressor gene.

Stages of Esophageal Cancer

• Stage 0 (in situ): Cancerous cells may be seen microscopically on the superficial layers of the esophageal lining but have yet to spread to the deeper parts of the inner lining of the esophagus.
• Stage I: The cancer arises from the superficial layers and has started spreading to the first layers of the inner esophageal lining and may have invaded nearby lymph nodes.
• Stage II: The cancer has spread to the deeper muscular layers of the esophagus and could have invaded nearby lymph nodes.
• Stage III: The cancer has invaded the deepest layers of the esophageal wall and spread to neighboring tissues or lymph nodes.
• Stage IV :The cancer has metastasized to other parts of the body.

Early esophageal cancer does not usually cause signs or symptoms, which usually appear only when the cancer has reached an advanced stage. 

Patients of esophageal cancer usually complain of dysphagia (difficulty swallowing) which usually becomes worse over time. It usually starts for solid food then semi solid foods then liquids.

Patients may also complain of retrosternal chest pain, chest discomfort, unintentional weight loss, heartburn, chronic cough, pneumonia and odynophagia (painful swallowing).

Other symptoms of esophageal cancer may include hoarseness, vomiting, hiccups, bone pain and bleeding into the esophagus (detected by blood appearing in the stools) and possibly anemia as a result of the esophageal bleeding.

• Medical history and physical exam

Diagnosis of esophageal cancer begins by taking a detailed patient history and performing a physical examination. The physical exam may be not helpful except for metastatic cases where findings of hepatomegaly (enlarged liver) or enlarged lymph nodes may be present.

Patients who display abnormal physical exam results are referred for further treatment .

• Imaging tests

The imaging tests are primarily used to stage esophageal cancer.

• computed tomography (CT)  scan

A CT scan is not usually used to diagnose esophageal cancer. However, it may be used to determine the location of the cancer and whether the cancer has metastasized and to which nearby structures.

CT scans are used to guide a biopsy needle into an area of suspected cancer spread.

• positron emission tomography )PET( scan

PET scan may be useful in detecting occult distant lymph node metastases (metastases that are hidden or not easily seen) and whether the cancer has spread to the bones.

• Endoscopic ultrasound

Endoscopic ultrasound is the test with the best sensitivity to verify the depth of tumor penetration and the presence of enlarged lymph nodes surrounding the esophagus, important factors for staging of the cancer.

• Barium swallow 

Barium swallow is a test that may show any abnormal areas in the surface of the inner lining of the esophagus, as such it may be able to detect small early cancers. It is usually performed when a patient complains of difficulty swallowing. The test has a high sensitivity to detect strictures (narrowing of the esophagus) and intraluminal masses. The test does not help in staging the cancer as it cannot display if and how far the cancer has spread.

The test may be helpful for examining the distal anatomy in obstructive tumors that cannot be accessed by endoscopy.  It may also be used to detect the presence of a tracheo-esophageal fistula (a hole in the tissue separating the esophagus and trachea), which is a serious complication of esophageal cancer that may lead to consistent coughing and pneumonia.

• Magnetic resonance imaging (MRI) scan

MRI scans are useful in examining the brain and spinal cord, but they usually not required to determine the spread of esophageal cancer. 

• Endoscopic procedures:

• Upper gastrointestinal (GI) endoscopy and biopsy:

This test allows the physician to clearly the examine the wall of the esophagus and identify any abnormal areas.  The test also provides information regarding the size and spread of the tumor, which may be used to help ascertain if the tumor can be removed using surgery.  A biopsy may be taken during the endoscopy and analyzed.

• Bronchoscopy 

This test may be done for cancers that affect upper part of the esophagus. The test is used to determine whether the cancer has metastasized to the trachea or bronchi.

• Thoracoscopy and laparoscopy  

These test allow the physician to examine lymph nodes and other organs close to the esophagus inside the chest (by thoracoscopy) or the abdomen (by laparoscopy) using a hollow lighted tube.

• Laboratory Studies

Laboratory studies in patients with esophageal cancer primarily focus on factors that could affect treatment options. They include CBC, comprehensive metabolic panel (CMP), particularly in alcoholic patients. Nutritional status should be assessed in patients with dysphagia (difficulty swallowing).

The method of treatment for esophageal cancer depends on the stage of the cancer, involvement of other organs, the location of the tumor, the type of cancer, ability of the patient to tolerate major surgeries, chemotherapy or radiation therapy and the patient’s overall health.

• Surgical treatments

For certain early stage esophageal cancers, surgery may be an option to attempt to remove the cancer and some of the normal tissue surrounding the tumor. In some cases, other treatments such as chemotherapy and/or radiation therapy are used in addition to surgery.

• Esophagectomy

It is the most common surgical treatment for esophageal cancer. In an esophagectomy part of the esophagus is removed in addition to the lymph nodes nearby. Often, a small portion of the stomach is removed as well 

• Radiation therapy

Radiation therapy could be used as a treatment option for esophageal cancer. Radiation therapy can be used in different cases:

Radiation therapy may be used along with chemotherapy as the main treatment method (chemoradiation), usually for patients who are not healthy enough to tolerate surgery or for those who refuse to undergo surgery.

It may be used before surgery (with or without chemotherapy) to attempt to shrink the tumor, making it easier to take out (called neoadjuvant treatment).

 It may be used after surgery (possibly with chemotherapy), to try destroy any cancer cells that may have been left behind but are too small to see (called adjuvant therapy).

It could be used as part of palliative therapy, to reduce the symptoms of advanced esophageal cancer such as pain, bleeding, or trouble swallowing.

Two main types of radiation therapy are used to treat esophageal cancer, external-beam radiation therapy and internal radiation therapy (brachytherapy).

• External-beam radiation therapy

The type is the most commonly used type of radiation therapy for esophageal cancer patients. A machine outside the body focuses the radiation on the cancer cells.

• Internal radiation therapy (brachytherapy)

The radioactive material is placed inside the body, close to the cancer cells, for a short period of time by use of an endoscope.

• Chemotherapy 

Chemotherapy drugs are either taken orally or injected intravenously. 

Chemotherapy may be used at different times during treatment for esophageal cancer.

It may be used after surgery (possibly with radiotherapy), to try destroy any cancer cells that may have been left behind but are too small to see (called adjuvant therapy).

It may be used before surgery (usually with radiotherapy) to attempt to shrink the tumor, making it easier to take out (called neoadjuvant treatment). 

It could be used as part of palliative therapy for advanced cancers that have metastasized to reduce the symptoms. In these cases the chemotherapy is not expected to cure the cancer, however it usually helps patients live longer. 

The following are common chemotherapy medications and medication combinations used for the treatment of esophageal cancer :

• Carboplatin and paclitaxel (could be used with radiation).
• Cisplatin and 5-fluorouracil (5-FU) (frequently used with radiation).
• ECF: epirubicin, cisplatin, and 5-FU .
• DCF: docetaxel, cisplatin, and 5-FU.
• Cisplatin with capecitabine .
• Oxaliplatin and either 5-FU or capecitabine.
• Irinotecan .

• Targeted Therapy

Targeted drugs may be used either in combination with chemotherapy or alone if chemotherapy is not working anymore. Targeted drugs include trastuzumab (the most commonly used) and ramucirumab. These drugs target specific proteins involved in cancer cell growth, disabling further growth of these cells. The harm that occurs to normal cells from these drugs is limited . 

• Endoscopic Treatments

• Endoscopic mucosal resection

Endoscopic mucosal resection (EMR) may be used to treat dysplasia (pre-cancerous growths) and some small, very early stage, esophageal cancers. Using this method, a part of the inner esophageal lining is removed.

• Photodynamic therapy 

In Photodynamic therapy (PDT) a light-activated drug is used to destroy the cancerous cells.  PDT can be used to treat dysplasia (pre-cancerous growths), Barrett’s esophagus, and some small, very early stage, esophageal cancers. It may also be used to treat large cancers where the esophagus is blocked. In that case, PDT is not used to kill all the cancer, but to destroy enough of it to improve a person’s capacity to swallow.

• Radiofrequency ablation (RFA) 

This procedure can be used to treat dysplasia. It may decrease the possibility of cancer developing in that area. In RFA a high-frequency electrical current is used to destroy the precancerous cells.

• Laser ablation  

This procedure may be used to help open the esophagus if it is blocked by an advanced cancer. This can improve a person’s capacity to swallow.

• Argon plasma coagulation

This procedure may be used to help open the esophagus if it is blocked by an advanced cancer. This can improve a person’s capacity to swallow.

• Electrocoagulation (electrofulguration) 

This procedure may be used to help open a blocked esophagus. This can improve a person’s capacity to swallow.

• Esophageal stent

A stent is a tube is a tube inserted in the esophagus to keep it open.

Esophageal malignancies can lead to esophageal bleeding.  Complications may result as a consequence of chemotherapy, radiotherapy and surgery.

Side effects of radiation therapy

The most frequent side effects encountered by patients who undergo radiation are:

•             The skin changes in the location where the radiation is used.

•             Fatigue (tiredness) .

•             Nausea and vomiting.

•             Diarrhea.

•             Painful sores in the mouth and throat.

•             Dry mouth or thick saliva.

Side effects of chemotherapy

The most frequent side effects encountered by patients who undergo chemotherapy include:

•             Nausea and vomiting

•             Loss of appetite

•             Hair loss

•             Painful sores in the mouth

•             Diarrhea or constipation

•             Low blood counts

•             Increased chance of infection

•             Easy bleeding or bruising

•             Fatigue

Complications after surgery

Possible complications encountered by patients who undergo surgery include:

•             Weakness and fatigue

•             Eating problems

•             Infections

•             Leaks where the remainder of the esophagus is joined to the stomach or the bowel.

•             Breathing problems

•             Heart problems

•             Voice changes

•             Delayed emptying of the stomach and acid reflux

•             A leak in the thoracic duct, with chyle leaking into the chest as a result.

•             Excess bleeding

•             Blood clots in the lungs or elsewhere

•             Strictures (narrowing) can form where the esophagus is surgically connected to the stomach, which can cause problems swallowing for some patients.

The risk of developing esophageal cancer may be decreased by making lifestyle changes such as: 

• Avoiding smoking and alcohol.
• Increasing fruit and vegetable consumption.
• Maintaining a healthy weight.
• Receiveing treatment for gastroesophageal reflux disease or Barrett’s esophagus.
• Tring not to drink very hot beverages.
• Staing away from chewing betel quid.

The prognosis of esophageal cancer depends on factors like the stage the cancer was detected ، In the majority of cases, esophageal cancer is treatable, but seldom curable. The overall 5-year survival rate in patients who agree to follow the physician’s treatment plan ranges from 5% to 30%. Occasionally, the disease may be detected very early in some patients. These patients have a better chance of survival .   People with adenocarcinomas are usually thought to have a somewhat better prognosis overall compared to people with squamous cell carcinomas. 

Esophageal cancer is the eighth most common cancer worldwide and is the sixth highest cause of cancer mortality .  According to the World Cancer Research Fund International, 456,000 new cases of esophageal cancer were diagnosed in 2012, accounting for 3.2% of all cancers . Worldwide, 81% of cases occurred in less developed countries and the highest incidence of cancer was in Asia, Africa, and the lowest incidence in Northern America and Europe.