Definition

Esophageal cancer is an aggressive tumor with an increasing number of cases in the Western world. Esophageal cancer is the seventh leading cause of death from cancer among American men. Worldwide, esophageal cancer is the sixth leading cause of death from cancer. In the United States alone, the National Cancer Institute reported 13,900 new cases and 13,000 deaths from esophageal cancer in 2003, 16,470 new cases and 14,539 deaths in 2009, and an estimated 16,640 new cases and 14,500 deaths in 2010.

There are two common types of esophageal cancer: adenocarcinoma and squamous cell carcinoma. Historically, squamous cell carcinoma of the esophagus was the most common esophageal cancer, accounting for more than 90 percent of esophageal cancers in the world. In the last three decades, there has been a rapid rise in the incidence of esophageal adenocarcinoma. In fact, the rate of increase has been higher than for any other cancer in the United States. Esophageal adenocarcinoma is now the predominant esophageal cancer in the Western world. 

Causes

Adenocarcinoma of the Esophagus

The most common risk factors include:

Gastroesophageal reflux disease

• Patients with recurring symptoms of reflux have an eightfold increase in the risk of esophageal adenocarcinoma.  

Barrett’s esophagus

•  It is known that Barrett’s esophagus develops in approximately 5 percent to 8 percent of patients with gastroesophageal reflux disease (GERD). With continued irritation of the lining of the esophagus caused by GERD, some patients will develop further cellular damage. These changes happen in a sequence. The damage to the cells may progress to low-grade dysplasia (abnormal cells), which then transforms to high-grade dysplasia (precancerous cells), and finally to invasive adenocarcinoma. The incidence of low-grade dysplasia, high-grade dysplasia and esophageal adenocarcinoma is approximately 4 percent, 1 percent and 0.5 percent per year, respectively, in patients with Barrett’s esophagus.

Squamous Cell Carcinoma of the Esophagus

Any factor that causes damage to the lining of the esophagus appears to increase the risk of squamous cell carcinoma of the esophagus. The known risk factors include:

• Alcohol use
• Tobacco use  

Patients who use both tobacco and alcohol have a higher risk of developing squamous cell carcinoma of the esophagus.The risk of squamous cell carcinoma of the esophagus is higher in patients with achalasia.

Symptoms

At a very early stage, esophageal cancer may not show any symptoms and will only be detected during an upper endoscopy and biopsy.

At more advance stages, the following symptoms can be present: 

• Dysphagia (difficulty swallowing)
• Weight loss, fatigue, weakness, loss of appetite
• Odynophagia (painful swallowing)
• Hoarseness (change in voice)
• Cough
• Mass in the neck (due to enlarged lymph nodes)
• Pain behind the breast bone
• Blood in the stool (bleeding from the tumor into the intestines)

Diagnosis

Upper endoscopy

Upper endoscopy is the most important study for the diagnosis of esophageal cancer and shows the presence of a mass or a nodule (small mass) in the esophagus. Further, it allows obtaining biopsies to confirm the presence of cancer cells in the lining of the esophagus.

Computed tomography scan (CT scan)

A CT scan uses X-rays to make detailed pictures of the structures inside the body. It allows the physician to assess the spread of the tumor to other structures around the esophagus, to the lymph nodes and to other organs such as the liver.

FDG-PET (¹⁸F-Fluoro-2- Deoxy-D-Glucose positron emission tomography)

This study identifies tumor cells based on their uptake of glucose. The higher a cell’s uptake of glucose, the higher the chance for that cell to be cancerous. FDG-PET is used to better detect the presence of cancer cells in the lymph nodes or in other organs such as the liver.

Endoscopic ultrasound

Endoscopic ultrasound (EUS) is performed using a probe via an upper endoscopy to assess the depth of the tumor (how deep the tumor has penetrated into the wall of the esophagus) and the involvement of lymph nodes around the esophagus. Biopsies of the lymph nodes can be performed at the same time. Many masses may be largely protruding into the interior of the esophagus and surprisingly do not involve the entire wall of the esophagus. Therefore, this study allows a more accurate assessment of the depth of penetration of the tumor and a better assessment of lymph nodes.

Endoscopic mucosal resection

With this endoscopic technique, the part of the lining of the esophagus which contains abnormal or cancerous cells is removed.  This technique allows for a better examination of the lining of the esophagus and identifies with precision how deep the tumor has penetrated into the walls of the esophagus.

Flexible bronchoscopy

Flexible bronchoscopy should be performed for tumors located in the upper and middle thirds of the esophagus to look for tumor invasion into the trachea (windpipe).

Staging

Staging of the esophageal cancer is similar to other solid cancers and is based on the size of the tumor, involvement of lymph nodes and spread of the tumor to other organs such as the liver.

Esophageal cancer TNM classification

T: Size of the Tumor

N: Involvement of lymph Nodes

M: Presence of Metastasis (spread of the tumor to other organs such as the liver)

Surveillance (Early Detection)

It is known that Barrett’s esophagus develops in approximately 5 percent to 8 percent of patients with gastroesophageal reflux disease (GERD). With continued irritation of the lining of the esophagus caused by GERD, some patients will develop further cellular damage. These changes happen in a sequence. The damage to the cells may progress to low-grade dysplasia (abnormal cells), which then transforms to high-grade dysplasia (precancerous cells), and finally to adenocarcinoma. The incidence of low-grade dysplasia, high-grade dysplasia and esophageal adenocarcinoma is approximately 4 percent, 1 percent and 0.5 percent per year, respectively, in patients with Barrett’s esophagus.

The challenge in dealing with esophageal cancer is that half of the patients have advanced disease and unresectable tumor (the tumor cannot be removed) when diagnosed. If a screening program could detect the disease at an earlier stage, there could be a greater possibility of cure. The increasing awareness of Barrett’s esophagus as a precursor to esophageal adenocarcinoma has led to the development of surveillance programs, which has allowed earlier detection of esophageal cancer.

We advise our patients with Barrett’s esophagus to have yearly endoscopy, and we increase the frequency to every three to six months for patients with dysplasia (abnormal cells). The Practice Parameters Committee of the American College of Gastroenterology has recently suggested that surveillance may be extended to every two to three years in patients with Barrett’s esophagus without dysplasia. For patients with low-grade dysplasia, they recommend that surveillance endoscopy be performed at six-month intervals for the first year, and subsequently done once a year if there has been no change.

Treatment

Endoscopic Treatment 

Endoscopic mucosal resection (EMR)

With this endoscopic technique, the part of the lining of the esophagus which contains abnormal or cancerous cells is removed.  This technique is used in a selected group of patients with esophageal cancer with only small areas of superficial tumor or high-grade dysplasia (abnormal cells in the lining of the esophagus).  Following endoscopic mucosal resection, patients need to be followed very carefully with serial endoscopies and biopsies to assure that there is no residual tumor (tumor left behind) or recurrence of tumor growth in the esophagus.

Surgical Treatment

Esophagectomy

Esophagectomy, including complete removal of the tumor and the surrounding lymph nodes, is the primary curative therapy for patients with resectable esophageal cancer. It is known that complete removal of the tumor and the number of lymph nodes removed at the time of surgery, affect the survival of patients with esophageal cancer.

After removal of the esophagus, the stomach, the colon (large intestine), or small bowel in selected cases, are used to replace the esophagus. When the stomach is used to replace the esophagus, the procedure is called “esophagectomy and gastric pull-up.” When the colon is used to replace the esophagus, the procedure is called “esophagectomy and colon interposition.” When the small bowel is used to replace the esophagus, the procedure is called “esophagectomy and jejunal interposition.”

Advances in techniques of surgery and patient care following surgery have allowed esophagectomy to be performed with great safety and superior outcomes. The most important factor to improve survival of patients with esophageal cancer is to remove the entire tumor and all the lymph nodes around the esophagus. There have been an increasing number of reports from high-volume centers indicating improvement in outcome and survival of patients who undergo esophagectomy for esophageal cancer. Patients stay in the hospital for seven to 10 days, on average. They will be on a soft diet for about eight weeks, and then gradually return to their regular eating habits.

Types of esophagectomy

Different types of esophagectomy are performed based on the location of the tumor, the depth of the tumor (how deep the tumor has penetrated into the wall of the esophagus), the patient’s overall state of health and the surgeon’s preference.

The most common types of esophagectomy include:

1. Transthoracic esophagectomy

   Transthoracic esophagectomy is performed by removing the esophagus through an incision in the right chest.  A second incision is then made in the abdomen to use the stomach or the colon (large intestine) to replace the esophagus. To restore swallowing, the small remaining upper part of the esophagus is then connected to the stomach (a gastric pull-up procedure) or the colon (a colon interposition), either in the right chest or in the neck (by making a third incision in the neck).

   En-bloc esophagectomy is a transthoracic esophagectomy which involves removal of the esophagus and all the tissues and lymph nodes around the esophagus via an incision in the right chest. A second incision is then made in the abdomen to use the stomach or the colon (large intestines) to replace the esophagus. To restore swallowing, the small remaining upper part of the esophagus is then connected to the stomach (a gastric pull-up procedure) or the colon (a colon interposition) in the neck, by making a third incision in the neck.

2. Thoracoabdominal esophagectomy

   This technique is performed by making an incision in the left chest. The diaphragm is then opened and the incision is extended to the abdomen. The mid and the lower part of the esophagus are then removed. To restore swallowing, the stomach is then connected to the remaining upper part of the esophagus in the chest, a procedure called gastric pull-up.

3. Transhiatal esophagectomy

   Transhiatal esophagectomy is performed via an incision in the abdomen for removal of the esophagus. The stomach or the colon (large bowel) is then used to replace the esophagus. To restore swallowing, the small remaining upper part of the esophagus is then connected to the stomach (a gastric pull-up procedure) or the colon (a colon interposition) by making a second incision in the neck.

4. Vagal-sparing esophagectomy

Vagal-sparing esophagectomy removes the esophagus while preserving the vagus nerves. These nerves, called the vagal plexus, are located around the esophagus and, among other things, are responsible for the function of the stomach and small bowel.

The nerves of the vagal plexus around the esophagus are shown in the image below. 

Following vagal-sparing esophagectomy, patients will have a better eating ability and fewer problems with symptoms, such as diarrhea, which may be present after other types of esophagectomy. In this procedure, an incision is made in the abdomen and the esophagus is removed but the vagus nerves are preserved. To restore swallowing, the stomach or the colon (large bowel) is then used to replace the esophagus and is connected to the small remaining part of the esophagus in the neck via a neck incision. If the stomach is used, to replace the esophagus the procedure is called a gastric pull-up. If the colon is used to replace the esophagus, the procedure is called colon interposition.  

Schematic Presentation of Vagal Sparing Esophagectomy and Colon Interposition

5. Minimally invasive esophagectomy

   This approach is performed by making small incisions in the abdomen and in the chest for removal of the esophagus. The stomach is most commonly used for esophageal replacement. To restore swallowing, the stomach is then connected to the remaining part of the esophagus in the chest or in the neck via a neck incision, a procedure called gastric pull-up. Studies have shown that this procedure can be performed with less morbidity and comparable oncologic results, compared to a standard esophagectomy.

 

The graphic below shows the different types of esophagectomy.

Schematic Presentation of Different Types of Esophagectomy

Radiation Therapy

Radiation therapy, or radiotherapy, involves the use of high-energy rays to destroy cancer cells. Radiation therapy is commonly used to reduce the size of a tumor prior to surgery. In patients with squamous cell carcinoma located in the upper part of the esophagus, radiation therapy in combination with chemotherapy is used for definitive treatment.

Chemotherapy

Chemotherapy involves the use of drugs to destroy cancer cells. Chemotherapy is commonly used to reduce the size of a tumor prior to surgery or to destroy any tumor cells in the lymph nodes following surgery. In patients with squamous cell carcinoma located in the upper part of the esophagus, chemotherapy in combination with radiotherapy is used for definitive treatment.