What is the Esophagus?
The esophagus is a muscular tube-like structure that connects the mouth to the stomach in the digestive system. It is approximately 25 centimeters long and runs behind the trachea (windpipe) and in front of the spinal column.
When a person swallows, muscles in the esophagus contract to move food or liquids down towards the stomach through a process called peristalsis. The esophageal sphincter, a ring of muscle at the bottom of the esophagus, relaxes to allow the food to enter the stomach and then contracts to prevent stomach contents from flowing back into the esophagus.
What is Esophageal Cancer?
Esophageal cancer, also called esophagus cancer, begins in the cells that line the esophagus.
Specifically, cancer of the esophagus begins in the inner layer of the esophageal wall and grows outward. If it spreads through the esophageal wall, it can travel to lymph nodes, which are the small, bean-shaped organs that help fight infection, as well as the blood vessels in the chest and other nearby organs. Esophageal cancer can also spread to the lungs, liver, stomach, and other parts of the body.
Types of Esophageal Cancer
There are two main types of esophageal cancer –
Small cell carcinoma
This type of cancer starts in the squamous cells, which are flat, thin cells that line the upper part of the esophagus. Squamous cell carcinoma is usually found in the upper and middle parts of the esophagus and is often linked to smoking and heavy alcohol consumption.
Adenocarcinoma
This type of cancer starts in the glandular cells that produce mucus and other fluids. Adenocarcinoma is typically found in the lower part of the esophagus near the stomach and is often associated with gastroesophageal reflux disease (GERD) and Barrett’s esophagus, a condition in which the lining of the esophagus is damaged by stomach acid and undergoes changes that increase the risk of cancer.
Less common types of esophageal cancer include small cell carcinoma, which is a type of neuroendocrine tumour, and sarcoma, which affects the connective tissues in the esophagus. These types of esophageal cancer are usually treated differently from squamous cell carcinoma and adenocarcinoma.
Risk Factors of Esophageal Cancer
There are several risk factors that can increase a person’s likelihood of developing esophageal cancer. Some of the most common risk factors include –
Tobacco
Using any form of tobacco, such as cigarettes, cigars, pipes, chewing tobacco, and snuff raises the risk of esophageal cancer, especially squamous cell carcinoma.
Alcohol
Drinking alcohol in large amounts on a regular basis can increase the risk of esophageal cancer.
Barrett's esophagus
This condition can develop in some people who have chronic gastroesophageal reflux disease (GERD) or inflammation of the esophagus called esophagitis, even when a person does not have symptoms of chronic heartburn. Damage to the lining of the esophagus causes the squamous cells in the lining of the esophagus to turn into glandular tissue. People with Barrett’s esophagus are more likely to develop adenocarcinoma of the esophagus, but the risk of developing esophageal cancer is still fairly low.
Obesity
A diet that is low in fruits and vegetables and high in processed foods and red meat may increase the risk of esophageal cancer.
Human papillomavirus (HPV)
Researchers are investigating HPV as a possible risk factor for esophageal cancer, but there is no clear link that squamous cell esophageal cancer is related to HPV. Sexual activity with someone who has HPV is the most common way someone gets HPV.
It’s important to note that having one or more of these risk factors does not necessarily mean that a person will develop esophageal cancer, and some people who develop the disease may not have any known risk factors.
Symptoms of Esophageal Cancer
Esophageal cancer may not cause any symptoms in its early stages, which can make it difficult to detect. As the cancer grows, it can cause a range of symptoms, including –
- Difficulty swallowing (dysphagia): This is the most common symptom of esophageal cancer. It may start with difficulty swallowing solid foods, and eventually progress to difficulty swallowing liquids as well.
- Painful swallowing: Some people may experience pain when swallowing food or liquids.
- Chest pain: Esophageal cancer can cause a burning or aching sensation in the chest.
- Unintentional weight loss: People with esophageal cancer may lose weight without trying.
- Hoarseness: Cancer in the esophagus can affect the nerves that control the vocal cords, leading to hoarseness.
- Coughing: Some people with esophageal cancer may develop a persistent cough.
- Vomiting or coughing up blood: Advanced esophageal cancer can cause bleeding in the esophagus, which may result in vomiting or coughing up blood.
Solid food followed by liquid food dysphagia is the most common complaint. Symptoms unfortunately only become apparent when the disease is advanced. Physical findings other than cachexia and palpable supraclavicular lymph nodes are rare.
Diagnoses of Esophageal Cancer
If esophageal cancer is suspected based on a person’s symptoms or risk factors, several diagnostic tests may be used to confirm the diagnosis and determine the extent of the cancer. These tests may include –
Preliminary studies:
These include physical examination, CBC, LFT, chest radiograph, esophagoscopy, and barium esophagogram. Brushings can be obtained, and lesions can undergo biopsy using endoscopy.
CT scan:
staging predicts invasion or metastases with an accuracy rate of >90% for the aorta, tracheobronchial tree, pericardium, liver, and adrenal glands; 85% for abdominal nodes; and 50% for paraesophageal nodes.
Endoscopic ultrasound (EUS):
EUS is more accurate than CT in assessing tumour depth and allows for lymph node sampling.
Positron emission tomography (PET):
PET is a useful diagnostic tool and has a greater sensitivity for the detection of nodal metastases when compared with CT. It has now become part of the diagnostic workup of patients with esophageal cancers.
Laparoscopy:
This allows assessment of subdiaphragmatic, peritoneal, liver, and lymph node metastases. In patients who are getting chemotherapy and radiation, either preoperatively or in lieu of surgery, placement of a jejunostomy tube (and not gastrostomy tube if an esophagectomy with stomach pull-up is planned) for enteral alimentation during laparoscopy is clinically useful. Thoracoscopy can allow patients who are noted to have intrathoracic dissemination to be spared radical resections.
Preventions and Treatments for Esophageal Cancer
Preventions to be considered are as follows
There is no guaranteed way to prevent esophageal cancer, but there are steps people can take to reduce their risk. Some preventive measures include –
- Stop smoking: Smoking is a major risk factor for esophageal cancer, so quitting smoking or not starting in the first place can help reduce the risk.
- Limit alcohol consumption: Heavy alcohol consumption is also a risk factor for esophageal cancer. Reducing or eliminating alcohol consumption can help lower the risk.
- Eat a healthy diet: Eating a diet rich in fruits, vegetables, whole grains, and lean protein sources can help reduce the risk of esophageal cancer. Avoiding processed foods and red meat may also be beneficial.
- Manage acid reflux: Chronic acid reflux, which is a risk factor for esophageal cancer, can be managed with lifestyle changes and medications prescribed by a doctor.
- Treat Barrett’s esophagus: People with Barrett’s esophagus, which is a precancerous condition, may need regular monitoring and treatment to prevent the development of esophageal cancer.
- Get regular screenings: People who are at higher risk of esophageal cancer may benefit from regular screenings to detect any changes in the esophagus early on.
Treatments required for Esophageal Cancer
The choice of treatment for esophageal cancer depends on the stage of the cancer, the location of the tumor, and the overall health of the patient. Treatment options for esophageal cancer may include –
Surgery is the removal of the tumor and some surrounding healthy tissue during an operation. A surgical oncologist is a doctor who specializes in treating cancer using surgery. Surgery has traditionally been the most common treatment for esophageal cancer. However, currently, surgery without previous chemotherapy or chemoradiotherapy is only used as the main treatment in specific situations.
For most people with locally advanced esophageal cancer, ASCO recommends chemoradiotherapy or chemotherapy before surgery because combined therapy has been shown to help people live longer (see below). After chemoradiotherapy and surgery, immunotherapy may be recommended if tumor cells are still found in the tissue removed during surgery. If surgery is not possible, the best treatment option is often a combination of chemotherapy and radiation therapy.
The following treatments use a long, flexible tube called an endoscope to treat the symptoms associated with esophageal cancer and to manage side effects caused by the tumour.
- Endoscopy and dilation. This procedure expands the esophagus. It may have to be repeated if the tumour grows.
- Endoscopy with stent placement. This procedure uses an endoscopy to insert a stent in the esophagus. An esophageal stent is a metal, mesh device that is expanded to keep the esophagus open.
- This type of palliative treatment helps destroy cancer cells by heating them with an electric current. This is sometimes used to help relieve symptoms by removing a blockage caused by the tumor.
- This is a type of palliative treatment that uses an endoscope with a probe attached that can freeze and remove tumour tissue. It can be used to reduce the size of a tumour to help a patient swallow easier.
Radiation therapy is the use of high-energy x-rays or other particles to destroy cancer cells. A doctor who specializes in giving radiation therapy to treat cancer is called a radiation oncologist. A radiation therapy regimen, or schedule, usually consists of a specific number of treatments given over a set period of time. The most common type of radiation treatment is called external-beam radiation therapy, which is radiation therapy given from a machine outside the body.
When radiation treatment is given directly inside the body, it is called internal radiation therapy or brachytherapy. For esophageal cancer, this involves temporarily inserting a radioactive wire into the esophagus using an endoscope.
There are different types of immunotherapy drugs that are approved to treat both adenocarcinoma and squamous cell carcinoma of the esophagus and the gastroesophageal junction, which is cancer that grows where the stomach and esophagus meet. Pembrolizumab (Keytruda) and nivolumab (Opdivo) are both checkpoint inhibitors that target the PD-1/PD-L1 pathway.
- Pembrolizumab (Keytruda):
- As a first-line treatment in combination with chemotherapy for incurable locally advanced or metastatic esophageal and gastroesophageal junction adenocarcinoma and squamous cell carcinoma, regardless of PD-L1 expression.
- As a first-line treatment in combination with chemotherapy and trastuzumab for HER2-positive incurable locally advanced or metastatic esophageal and gastroesophageal junction adenocarcinoma, regardless of PD-L1 expression.
- As a second-line treatment for esophageal squamous cell carcinoma that tests CPS positive at 10% or higher. CPS stands for “combined positive score” and it is a way to measure how many cells express the PD-L1 protein.
- It is also approved to treat gastroesophageal junction adenocarcinoma that tests positive for MSI-H or has mismatch repair deficiency after 1 or more chemotherapy treatments have not stopped the cancer.
- Denvax Immunotherapy:
Denvax is a treatment known as cancer immunotherapy. It boosts the immune system to fight against cancer, mostly solid tumours. Denvax is targeted therapy and comes under the 4th modality of cancer treatment called cancer Immunotherapy.
Dendritic cells are cells of the immune system that help in the fight against cancer. Denvax treatment is customized dendritic cell-based cancer immunotherapy. Denvax shows the most promise at preventing a recurrence of cancer after surgery, chemotherapy or radiation because the immune system will need to recognize and attack a smaller number of cancer cells.
- Nivolumab (Opdivo):
- As a first-line treatment in combination with chemotherapy for esophageal or gastroesophageal junction adenocarcinoma, regardless of PD-L1 expression.
- As a second-line treatment for esophageal squamous cell carcinoma, regardless of PD-L1 expression.
- As a post-surgery adjuvant treatment after chemotherapy, radiation, and surgery in esophageal and gastroesophageal adenocarcinoma and squamous cell carcinoma if any cancer cells remain in the tissue removed during surgery. Some research suggests that people with tumors with higher PD-L1 expression may have a greater benefit from adjuvant nivolumab, but this requires further study.
Chemotherapy alone is seldom an effective palliative modality of the primary tumor in patients with esophageal cancer. When chemotherapy is employed, it should be coupled with mechanical or radiotherapeutic approaches for palliation of dysphagia. As in gastric cancer, discussed later, multiagent chemotherapy-induced responses tend to be short-lived.
References:
- Manual of Clinical Oncology by Bartosz Chmeilowski and Mary Territo
- cancer.net
What is the Esophagus?
The esophagus is a muscular tube-like structure that connects the mouth to the stomach in the digestive system. It is approximately 25 centimeters long and runs behind the trachea (windpipe) and in front of the spinal column.
When a person swallows, muscles in the esophagus contract to move food or liquids down towards the stomach through a process called peristalsis. The esophageal sphincter, a ring of muscle at the bottom of the esophagus, relaxes to allow the food to enter the stomach and then contracts to prevent stomach contents from flowing back into the esophagus.
What is Esophageal Cancer?
Esophageal cancer, also called esophagus cancer, begins in the cells that line the esophagus.
Specifically, cancer of the esophagus begins in the inner layer of the esophageal wall and grows outward. If it spreads through the esophageal wall, it can travel to lymph nodes, which are the small, bean-shaped organs that help fight infection, as well as the blood vessels in the chest and other nearby organs. Esophageal cancer can also spread to the lungs, liver, stomach, and other parts of the body.
Types of Esophageal Cancer
There are two main types of esophageal cancer –
Small cell carcinoma
This type of cancer starts in the squamous cells, which are flat, thin cells that line the upper part of the esophagus. Squamous cell carcinoma is usually found in the upper and middle parts of the esophagus and is often linked to smoking and heavy alcohol consumption.
Adenocarcinoma
This type of cancer starts in the glandular cells that produce mucus and other fluids. Adenocarcinoma is typically found in the lower part of the esophagus near the stomach and is often associated with gastroesophageal reflux disease (GERD) and Barrett’s esophagus, a condition in which the lining of the esophagus is damaged by stomach acid and undergoes changes that increase the risk of cancer.
Less common types of esophageal cancer include small cell carcinoma, which is a type of neuroendocrine tumour, and sarcoma, which affects the connective tissues in the esophagus. These types of esophageal cancer are usually treated differently from squamous cell carcinoma and adenocarcinoma.
Risk Factors of Esophageal Cancer
There are several risk factors that can increase a person’s likelihood of developing esophageal cancer. Some of the most common risk factors include –
Tobacco
Using any form of tobacco, such as cigarettes, cigars, pipes, chewing tobacco, and snuff raises the risk of esophageal cancer, especially squamous cell carcinoma.
Alcohol
Drinking alcohol in large amounts on a regular basis can increase the risk of esophageal cancer.
Barrett's esophagus
This condition can develop in some people who have chronic gastroesophageal reflux disease (GERD) or inflammation of the esophagus called esophagitis, even when a person does not have symptoms of chronic heartburn. Damage to the lining of the esophagus causes the squamous cells in the lining of the esophagus to turn into glandular tissue. People with Barrett’s esophagus are more likely to develop adenocarcinoma of the esophagus, but the risk of developing esophageal cancer is still fairly low.
Obesity
A diet that is low in fruits and vegetables and high in processed foods and red meat may increase the risk of esophageal cancer.
Human papillomavirus (HPV)
Researchers are investigating HPV as a possible risk factor for esophageal cancer, but there is no clear link that squamous cell esophageal cancer is related to HPV. Sexual activity with someone who has HPV is the most common way someone gets HPV.
It’s important to note that having one or more of these risk factors does not necessarily mean that a person will develop esophageal cancer, and some people who develop the disease may not have any known risk factors.
Symptoms of Esophageal Cancer
Esophageal cancer may not cause any symptoms in its early stages, which can make it difficult to detect. As the cancer grows, it can cause a range of symptoms, including –
- Difficulty swallowing (dysphagia): This is the most common symptom of esophageal cancer. It may start with difficulty swallowing solid foods, and eventually progress to difficulty swallowing liquids as well.
- Painful swallowing: Some people may experience pain when swallowing food or liquids.
- Chest pain: Esophageal cancer can cause a burning or aching sensation in the chest.
- Unintentional weight loss: People with esophageal cancer may lose weight without trying.
- Hoarseness: Cancer in the esophagus can affect the nerves that control the vocal cords, leading to hoarseness.
- Coughing: Some people with esophageal cancer may develop a persistent cough.
- Vomiting or coughing up blood: Advanced esophageal cancer can cause bleeding in the esophagus, which may result in vomiting or coughing up blood.
Solid food followed by liquid food dysphagia is the most common complaint. Symptoms unfortunately only become apparent when the disease is advanced. Physical findings other than cachexia and palpable supraclavicular lymph nodes are rare.
Diagnoses of Esophageal Cancer
If esophageal cancer is suspected based on a person’s symptoms or risk factors, several diagnostic tests may be used to confirm the diagnosis and determine the extent of the cancer. These tests may include –
Preliminary studies:
These include physical examination, CBC, LFT, chest radiograph, esophagoscopy, and barium esophagogram. Brushings can be obtained, and lesions can undergo biopsy using endoscopy.
CT scan:
staging predicts invasion or metastases with an accuracy rate of >90% for the aorta, tracheobronchial tree, pericardium, liver, and adrenal glands; 85% for abdominal nodes; and 50% for paraesophageal nodes.
Endoscopic ultrasound (EUS):
EUS is more accurate than CT in assessing tumour depth and allows for lymph node sampling.
Positron emission tomography (PET):
PET is a useful diagnostic tool and has a greater sensitivity for the detection of nodal metastases when compared with CT. It has now become part of the diagnostic workup of patients with esophageal cancers.
Laparoscopy:
This allows assessment of subdiaphragmatic, peritoneal, liver, and lymph node metastases. In patients who are getting chemotherapy and radiation, either preoperatively or in lieu of surgery, placement of a jejunostomy tube (and not gastrostomy tube if an esophagectomy with stomach pull-up is planned) for enteral alimentation during laparoscopy is clinically useful. Thoracoscopy can allow patients who are noted to have intrathoracic dissemination to be spared radical resections.
Preventions and Treatments for Esophageal Cancer
Preventions to be considered are as follows
There is no guaranteed way to prevent esophageal cancer, but there are steps people can take to reduce their risk. Some preventive measures include –
- Stop smoking: Smoking is a major risk factor for esophageal cancer, so quitting smoking or not starting in the first place can help reduce the risk.
- Limit alcohol consumption: Heavy alcohol consumption is also a risk factor for esophageal cancer. Reducing or eliminating alcohol consumption can help lower the risk.
- Eat a healthy diet: Eating a diet rich in fruits, vegetables, whole grains, and lean protein sources can help reduce the risk of esophageal cancer. Avoiding processed foods and red meat may also be beneficial.
- Manage acid reflux: Chronic acid reflux, which is a risk factor for esophageal cancer, can be managed with lifestyle changes and medications prescribed by a doctor.
- Treat Barrett’s esophagus: People with Barrett’s esophagus, which is a precancerous condition, may need regular monitoring and treatment to prevent the development of esophageal cancer.
- Get regular screenings: People who are at higher risk of esophageal cancer may benefit from regular screenings to detect any changes in the esophagus early on.
Treatments required for Esophageal Cancer
The choice of treatment for esophageal cancer depends on the stage of the cancer, the location of the tumor, and the overall health of the patient. Treatment options for esophageal cancer may include –
Surgery is the removal of the tumor and some surrounding healthy tissue during an operation. A surgical oncologist is a doctor who specializes in treating cancer using surgery. Surgery has traditionally been the most common treatment for esophageal cancer. However, currently, surgery without previous chemotherapy or chemoradiotherapy is only used as the main treatment in specific situations.
For most people with locally advanced esophageal cancer, ASCO recommends chemoradiotherapy or chemotherapy before surgery because combined therapy has been shown to help people live longer (see below). After chemoradiotherapy and surgery, immunotherapy may be recommended if tumor cells are still found in the tissue removed during surgery. If surgery is not possible, the best treatment option is often a combination of chemotherapy and radiation therapy.
The following treatments use a long, flexible tube called an endoscope to treat the symptoms associated with esophageal cancer and to manage side effects caused by the tumour.
- Endoscopy and dilation. This procedure expands the esophagus. It may have to be repeated if the tumour grows.
- Endoscopy with stent placement. This procedure uses an endoscopy to insert a stent in the esophagus. An esophageal stent is a metal, mesh device that is expanded to keep the esophagus open.
- This type of palliative treatment helps destroy cancer cells by heating them with an electric current. This is sometimes used to help relieve symptoms by removing a blockage caused by the tumor.
- This is a type of palliative treatment that uses an endoscope with a probe attached that can freeze and remove tumour tissue. It can be used to reduce the size of a tumour to help a patient swallow easier.
Radiation therapy is the use of high-energy x-rays or other particles to destroy cancer cells. A doctor who specializes in giving radiation therapy to treat cancer is called a radiation oncologist. A radiation therapy regimen, or schedule, usually consists of a specific number of treatments given over a set period of time. The most common type of radiation treatment is called external-beam radiation therapy, which is radiation therapy given from a machine outside the body.
When radiation treatment is given directly inside the body, it is called internal radiation therapy or brachytherapy. For esophageal cancer, this involves temporarily inserting a radioactive wire into the esophagus using an endoscope.
There are different types of immunotherapy drugs that are approved to treat both adenocarcinoma and squamous cell carcinoma of the esophagus and the gastroesophageal junction, which is cancer that grows where the stomach and esophagus meet. Pembrolizumab (Keytruda) and nivolumab (Opdivo) are both checkpoint inhibitors that target the PD-1/PD-L1 pathway.
- Pembrolizumab (Keytruda):
- As a first-line treatment in combination with chemotherapy for incurable locally advanced or metastatic esophageal and gastroesophageal junction adenocarcinoma and squamous cell carcinoma, regardless of PD-L1 expression.
- As a first-line treatment in combination with chemotherapy and trastuzumab for HER2-positive incurable locally advanced or metastatic esophageal and gastroesophageal junction adenocarcinoma, regardless of PD-L1 expression.
- As a second-line treatment for esophageal squamous cell carcinoma that tests CPS positive at 10% or higher. CPS stands for “combined positive score” and it is a way to measure how many cells express the PD-L1 protein.
- It is also approved to treat gastroesophageal junction adenocarcinoma that tests positive for MSI-H or has mismatch repair deficiency after 1 or more chemotherapy treatments have not stopped the cancer.
- Denvax Immunotherapy:
Denvax is a treatment known as cancer immunotherapy. It boosts the immune system to fight against cancer, mostly solid tumours. Denvax is targeted therapy and comes under the 4th modality of cancer treatment called cancer Immunotherapy.
Dendritic cells are cells of the immune system that help in the fight against cancer. Denvax treatment is customized dendritic cell-based cancer immunotherapy. Denvax shows the most promise at preventing a recurrence of cancer after surgery, chemotherapy or radiation because the immune system will need to recognize and attack a smaller number of cancer cells.
- Nivolumab (Opdivo):
- As a first-line treatment in combination with chemotherapy for esophageal or gastroesophageal junction adenocarcinoma, regardless of PD-L1 expression.
- As a second-line treatment for esophageal squamous cell carcinoma, regardless of PD-L1 expression.
- As a post-surgery adjuvant treatment after chemotherapy, radiation, and surgery in esophageal and gastroesophageal adenocarcinoma and squamous cell carcinoma if any cancer cells remain in the tissue removed during surgery. Some research suggests that people with tumors with higher PD-L1 expression may have a greater benefit from adjuvant nivolumab, but this requires further study.
Chemotherapy alone is seldom an effective palliative modality of the primary tumor in patients with esophageal cancer. When chemotherapy is employed, it should be coupled with mechanical or radiotherapeutic approaches for palliation of dysphagia. As in gastric cancer, discussed later, multiagent chemotherapy-induced responses tend to be short-lived.
References:
- Manual of Clinical Oncology by Bartosz Chmeilowski and Mary Territo
- cancer.net
