Esophageal cancer is the sixth most common cause of cancer-related deaths worldwide and fourth in developing countries. The esophagus, also known as food pipe, is a muscular hollow tube-like organ that provides passage to swallowed food up to the stomach.
Based on the type of cells affected, esophagus cancer can be divided into two major histology types:
- squamous cells carcinoma (affecting flat cells that line the inner side of the esophagus) and
- adenocarcinoma (affecting glandular cells that produce mucus and other fluids).
Causes of Esophageal Cancer
Patient with squamous cell carcinoma are usually thin built due to the significant weight loss, and patient with adenocarcinoma are usually obese.
Smoking is a risk factor for both. Cessation of smoking reduces the risk for squamous cell carcinoma but not for adenocarcinoma. Moreover, the chances of cancer increases with the duration and intensity of smoking.
Diet rich in red and processed meat, saturated fats or cholesterol, increases the risk, whereas diet rich in raw fruits and vegetables, grains, fibers or carotenoids, decrease the risk of SQUAMOUS CELL AND ADENOCARCINOMA of esophagus.
Excessive alcohol consumption is a risk factor for SQUAMOUS CELL carcinoma but not for ADENOCARCINOMA, moreover, the risk increases with the duration and intensity of drinking.
Excessive consumption of hot beverages like tea and coffee also increases the risk of squamous cell carcinoma of esophagus.
Industrial or occupational exposure to gases or heavy metals, also increases the risk of squamous cell carcinoma.
Achalasia cardia is a condition in which there is failure of lower esophageal sphincter to relax after taking food, due to which there is retention of food particles, leading to chronic irritation and squamous cell carcinoma.
Gastroesophageal reflux disease is a condition in which there is a reflux of gastric contents, including gastic acid, into the esophagus, causing changes in the epithelium leading to barret’s esophagus, and adenocarcinoma. So these were the risk factors for esophageal carcinoma.
Chronic tobacco chewing or cigarette smoking exposes the esophagus cells to carcinogenic chemicals, which increases the risk of esophageal cancer. This has been identified as one of the major risk factors for esophageal cancer.
Excessive Alcohol Consumption
Chronic alcohol use irritates the esophagus by itself or it may render the esophagus susceptible to other carcinogens. Various population-based studies worldwide have shown that alcohol use can increase the risk of esophageal cancer in a dose-dependent manner.
Excessive consumption of hot beverages
Excessive drinking of hot liquids or eating hot food can cause thermal injury to the esophagus leading to esophageal cancer.
Gastroesophageal reflux disease (GERD)
It is a disorder in which stomach’s acidic content reflux into the esophagus, generally due to malfunctioning of the lower esophageal sphincter. Unlike stomach cells, esophagus cells are not capable of withstanding the acidic conditions. Thus, prolonged exposure of the lower esophagus to stomach acid content causes irritation of the cells in that region, which may lead to cancerous changes in the cells.
Occupational exposure to heavy metals or harmful gases/fumes also increases the risk of esophageal cancer.
It is a condition characterized by the accumulation of food in the lower esophagus due to incomplete relaxation of the lower esophageal sphincter. This causes irritation of esophagus by the retained food and increases the risk of esophageal cancer by several folds.
It is a condition in which pre-cancerous changes take place in the lower esophagus by reflux of stomach acid for a long time. This condition may arise due to certain disorders like GERD. Patients with Barrett’s esophagus are at a higher risk of developing esophageal cancer.
Higher age individuals, especially men are at significantly higher risk of developing esophageal cancer.
Diet deficient in fruits and vegetables, obesity, low socioeconomic status, infection with Helicobacter pylori or human papillomavirus (HPV), and certain hereditary disorders like Plummer–Vinson syndrome and tylosis have also shown to increase the risk of esophagus cancer.
Symptoms and Signs of Esophageal Cancer
Esophageal cancer is only the fifth most common type of cancer of the gastrointestinal tract; yet, abundant cases are reported each year in the US. As per the most recent statistics, collected from published literature in the PubMed library, 16, 940 annual cases are recorded in the country.
There are two main types of cancer in the esophagus, the squamous cell carcinoma, esophageal adenocarcinoma; the incidence of the latter being on the rise. Both these neoplasms present with similar signs and symptoms, which will be listed in this article.
The most common symptom of esophageal cancer is dysphagia or difficulty in eating, which is the first reported sign among maximum number of patients.
This may be accompanied by pain or may be a general feeling of an inability to swallow.
Dysphagia primarily occurs because of the reduction of esophageal lumen of the patient by 50 % because of the massive growth of the tumor.
Nausea and vomiting are other very common signs and symptoms of esophageal cancer, which may actually precede the occurrence of tumor in many cases.
It has been reported in the medical literature that the risk of esophaegal cancer in patients with GERD (gastro – esophageal reflux disease) is approximately 5 times higher than in a healthy individual.
GERD is marked by repeated feelings of nausea and vomiting, especially after a recent meal, and the sensation of heartburn / pain in the chest, which may increase upon lying down.
Since it is associated with both early stages of cancer and is also a major risk factor, this is one early sign you must be watchful for.
Often, individuals with esophageal cancer present with anemia at the time of their diagnosis, which is because of repeated bleeding of the gastrointestinal lumen.
Gastrointestinal bleeding is a symptom of esophageal cancer, which may not be perceptible to you because there is no evidence of bloody stools until at a very advanced stage of tumor, where it has progressed to the surrounding structures.
At that stage, you may notice melena (black tarry tools) or simply a speck of blood in your stool.
The confirmatory diagnosis of anemia also requires lab evaluations. But, it can be more easily noted on the basis of routine signs and symptoms like pale skin and fatigue. On the basis of these signs and symptoms, you can schedule a physician visit.
Similar to other types of cancer, esophageal cancer is also associated with weight loss, which may be more severe because of inability of the individual to take regular meals.
Unexplained weight loss and loss of appetite are its common signs.
Change in Dietary Patterns
One of the most peculiar signs of esophageal cancer is change in the dietary patterns of the patient. An increased preference towards softer foods and more liquid foods may develop because of the inability to swallow hard foods.
This change may often occur without conscious knowledge of the patient as an adaptation to their physical pain.
Other dietary changes that one may notice are taking time longer to finish the meals, chewing more slowly to form a smooth paste of food, increasing the intake of liquids such as tea, milk or soda along with solid meals.
Gradually, the person will try to omit meats and breads from their diet because of their inability to swallow, and may sometimes complain that the ‘food is stuck in their throat’.
At this stage, the tumor, and it’s associated dysphagia has clinically advanced and medical assistance must not be neglected at all.
As mentioned, burning sensation in the chest is a common symptom of esophageal cancer.
Some individuals may perceive it as chest pain because of the chronicity of its occurrence and may even have the false suspicion of cardiovascular disorders.
One way to distinguish cardiovascular condition from esophageal cancer is that the former may be associated with a feeling of tightness of the chest and is most likely accompanied by dyspnea (difficulty in breathing) while the latter is commonly associated with dysphagia and/or nausea.
Hematemesis or the presence of blood in your vomit is another sign of esophageal cancer.
This may not be seen every day. It is quite possible that you may notice blood once in a few months or weeks.
You must know that the presence of blood in your vomitus is not a physiological occurrence under any circumstance and must see your doctor immediately in case of this sign.
Cough and Breathlessness
Cough and difficulty of breathing arise as symptoms of esophageal cancer because of the difficulty in swallowing food and regurgitation in respiratory tract.
It may also occur due to locoregional extension to lungs or metastasis to lungs or pleura.
The presence of these symptoms will most likely make you suspicious of a pulmonary disorder. And, in fact, in some cases, even pneumonia – like symptoms may be noted.
Bottom line is that esophageal cancer does not present with very specific signs and symptoms, which often delays its diagnosis at an early stage. In a large percentage of patients, it is recorded as a chance occurrence because the signs and symptoms are so general that there is no suspicion at the patient’s end. However, you must note that daily episodes of GERD are associated with an all the more higher risk of esophageal cancer, approximately seven – fold higher than a healthy person. So, it is recommended to seek immediate treatment if you are faced with its symptoms.
Esophageal Cancer Staging
In the chest cavity, this trachea lies in front which helps us breathing. As you can see, behind the trachea lies the esophagus.
Heart also lies in the chest cavity in front of esophagus.
And on both sides, lie the lungs.
And as you can see in the figure, esophagus crosses the diaphragm to enter into the abdomen, where it joins the stomach.
Esophagus starts at a distance of 15 cm from upper incisors, at the level of cricopharyngeus muscle.
And the lowest most end of the esophagus is at distance of 40 cm from upper incisors, at the level of gastroesophageal junction.
So the total length of the esophagus is 25 cm. The upper 3 cm of esophagus is called as cervical esophagus.
And below that esophagus maybe divided into 3 parts – upper, middle and lower esophagus, as you can see in the figure.
Carcinoma rising from the upper and middle esophagus is mostly squamous cell carcinoma. Adenocarcinoma is seen very rarely in this region.
Whereas, in the lower 1/3d of the esophagus, it is mostly adenocarcinoma, although squamous cell carcinoma may also be seen.
So after knowing the anatomy of esophagus, now let’s discuss the staging for esophageal cancer.
Esophageal Cancer Staging
Staging for esophageal cancer is called as TNM staging system. It helps in disease prognostication and choosing an appropriate treatment strategy.
To understand the staging better, let’s understand the various layers of the esophageal wall.
This diagram is a magnified image of a cross-section of the wall of esophageal. Imagine the upper part is the inner side and the lower part is the outer side. The innermost layer is called as epithelium, followed by this layer, called as lamina propria.
Outer to the lamina propria is this layer called muscularis mucosa.
Outer to which, lies this layer which is called as submucosa. Then lies muscularis propria.
And on the outermost aspect, lies this layer which is called as serosa or adventitia.
Now let’s understand the staging of esophageal cancer based on this.
N0 – No spread to regional lymph nodes
N1 – Involvement of 1 to 2 regional lymph nodes
N2 – Involvement of 3 to 6 regional lymph nodes
N3 – Involvement of 7 or more regional lymph nodes This figure shows the regional lymph nodes for esophagus.
M0 – Tumor has not spread to distant sites.
M1 – Tumor has spread to distant sites like lungs, pleura, peritoneum, liver, bones, etc
Esophageal Cancer Staging Investigations
In this test, a thick, viscous liquid containing barium (a heavy element that reflects x-rays) is first swallowed. Then, x-rays are obtained for the upper gastrointestinal system where any abnormal area is detected by the irregular barium coating.
Endoscopy is a diagnostic technique which uses an endoscope – a long, flexible, slender tube usually equipped with a camera, a light source, and some special instruments for biopsy or surgery. This enables the doctors to look inside the body parts such as the esophagus, stomach, and duodenum to determine the abnormalities.
Upper Endoscopy: This is generally the first diagnostic test performed on a patient presented with the symptoms of stomach cancer. In this technique, the doctor examines for any abnormal areas in the wall of the stomach using an endoscope. Biopsy samples are generally collected from abnormal areas using a special biopsy instrument in conjunction with the endoscope.
Endoscopic Ultrasound: In this technique, an ultrasound device is used along with an endoscope, to determine the location and extent of tumor invasion in the stomach wall and nearby lymph nodes. It can also signal the spread of disease to nearby organs; however, it cannot accurately determine the extent of disease spread to distant organs such as lungs or bones.
One or more of the imaging tests are required for staging and reassessment-
- Computed tomography (CT) scan
- Magnetic resonance imaging (MRI) scan
- Positron emission tomography (PET) scan
Esophageal Cancer Treatment
First, we will discuss the treatment for localized esophageal cancer. Earlier stages of esophageal cancer are carcinoma in situ (Tis) and T1a.
Endoscopic mucosal resection is used for the treatment of Tis and T1a disease.
As you can see in the figure, only the superficial cancerous portion is removed, while the remaining tissue remains unaffected.
Esophagectomy or removal of esophageal is also an option for the early-stage disease but is practiced less commonly. As you can see in the figure, in esophagectomy, most of the esophagus is removed. And the stomach is pulled up to be joined to the remaining part of the esophagus. Now we come to the treatment for T1b disease, or the disease that infiltrates into the submucosa, without the involvement of lymph nodes. For T1b disease without lymph nodes involvement, esophagectomy is the preferred treatment. Now, we will discuss the treatment of T2 or T3 disease. That is the disease which has infiltrated into muscularis propria or serosa. And for the treatment of esophageal cancer, which has spread to the regional lymph nodes. In these cases, surgery alone may not be sufficient for the treatment, so different combination of surgery, radiotherapy and/or chemotherapy are used. Combination of modalities to be used is decided by oncologist on an individual basis, depending upon the exact stage of the, the comorbidities and the performance status of the patient (see above). Now we come to the treatment for T4 disease, in which the disease extends to involve the adjacent structures. In this figure, the disease has extended to involve the heart or pericardium. And here, cancer has spread to the great vessels of the heart. Here, it invades the lungs or pleura. And here, cancer has infiltrated into the diaphragm. And here it has spread to the trachea. In some cases of T4 disease, surgery may not be possible, so a combination of chemotherapy and/or radiation therapy may be used. And if it is possible, then surgical resection of the tumor, with or without chemotherapy and radiation therapy is done.
In T4 disease also, the decision to do surgery or not, and to give chemotherapy or radiotherapy is taken by the oncologist on an individual patient basis after assessing the exact stage of the disease and understanding the comorbidities and the performance status of the patient.
Now we come to the treatment for the metastatic disease, that is, the disease which has spread to the other organs. In this figure, it has spread to the lungs. And here, it has spread to the liver. It may also spread to the bones. In all these cases of metastatic disease, chemotherapy, targeted therapy and/or immunotherapy is the treatment of choice. But other modalities like surgery, radiation therapy or bone-directed therapy may be used for palliation and relief of symptoms.
Always remember that the treatment for metastatic disease is not generally curative, so the intent of the treatment is prolongation of life, reduction of symptoms and improvement in the quality of life of the patient. So this completes the treatment for esophageal cancer.
Esophageal Cancer Treatment Options
Following are the various treatment options for early and advanced stage esophageal cancer.
Esophageal cancer treatment options according to stage
Tis or T1a
Endoscopic resection with or without ablation is considered as the first choice of treatment. Surgery can be employed if the patient is medically fit
T1b N0 M0
Surgical resection of esophagus is the preferred treatment. Chemotherapy with/without radiotherapy if surgically unresectable or inoperable.
T1b N1-2 M0, T2-T4a N0-2 M0
Surgical resection in combination with chemotherapy with/without radiotherapy is the preferred treatment. Chemotherapy with/without radiotherapy if surgically unresectable or inoperable.
Cervical esophagus inv. OR T4b N0-2 M0
Chemotherapy with/without radiotherapy is the standard treatment.
Any T Any N M1 (Metastatic disease)
Chemotherapy is the mainstay of treatment in case the disease has spread to distant body parts. Immunotherapy is also a treatment option in such cases. Along with the chemotherapy, radiotherapy and/or surgery may be employed as palliative therapy as and when required.
Endoscopic treatments for Early Stage Disease
Various endoscopic treatment options are now available for the treatment of some early-stage esophageal cancers or for providing symptomatic relief from advanced stage disease. Treatments like endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), and endoscopic ablation, mainly aim to treat very early stage esophageal cancers. Other treatments like laser ablation, esophageal stent or feeding tube placement, mainly aim to relieve symptoms of more advanced staged esophageal cancers.
Role of Targeted Therapy
Role of Immunotherapy
Pembrolizumab may be used as the second-line or subsequent line therapy for MSI-H or dMMR positive unresectable/metastatic esophagus/EGJ/gastric tumors that have progressed on prior treatment and for which no satisfactory alternative treatment option is available.
Role of Chemotherapy
Chemotherapy may be used for esophageal cancer treatment as neoadjuvant therapy (given before surgery to downstage the tumor), concurrent therapy (given along with radiation), adjuvant therapy (given after surgical resection of tumor) and palliative therapy (in cases of metastatic disease).
Some chemotherapy drugs used as a part of esophageal cancer treatment regimens are-
- Paclitaxel, Docetaxel
- Carboplatin, Cisplatin, Oxaliplatin
- 5 Fluorouracil
Best Esophageal Cancer Specialist in Delhi
Dr Sunny Garg is a renowned Medical Oncologist in New Delhi with an experience of around 10 years of treating esophageal cancer patients. He has treated esophageal cancer patients with Chemotherapy, Targeted Therapy, Immunotherapy and Personalized Cancer Treatment. He is currently practicing at Manipal Hospital, Dwarka.
Diagnostic modalities available at our hospital include Endoscopic biopsy, Endoscopic Ultrasound, Barium Swallow, Whole Body PET CT, etc. Other treatment facilities for Esophageal Cancer available are Esophagectomy, Transthoracic Esophagectomy, Transhiatal Esophagectomy, Endoscopic Mucosal Resection, Radiofrequency Ablation, Minimally Invasive Surgery, Radiation Therapy, etc.
Call +91 9686813020 for appointment.