Esophageal Cancer
An Article by Dr. William D. Lyday
The goal of this summary is to help those affected by esophageal cancer, their families and friends. This is a complicated disease and unless you went to medical school, it is pretty tough to read medical books and literature online and have it make any sense. Even if you have no medical knowledge , it is important to have a few basic facts straight that can make a huge difference in your care. We will start with this bullet point review and later, go into more discussion of the details.
Important Facts
- A test known as an EGD or upper endoscopy is needed to confirm the diagnosis of esophgeal cancer. Biopsies of your esopahgus are taken during this procedure and sent to a pathologist who looks under a microscope and confirms cancer is present.
- Esophageal cancer is sneaky and often silent until it is very advanced. In the United States and other Western countries, heartburn is the primary risk factor, particularly in white males over 40 yo.
- There are two main types of esophageal cancer and they have different treatments and outcomes. Make sure you know which one you have a) adenocarcinoma or b) squamous cell carcinoma. Adenocarcinoma tends to occur in the lower esophagus and is often assicated with a pre cancer known as Barrett’s esophagus. Barrett’s esophagus is commonly found in patients with heartburn and needs to be managed – more later. Adencarcinoma is most often caused by chronic acid reflux. On the other hand, squamous cell carcinoma tends to occur in a different location in the mid and upper esophagus. Squamous cancer is highly associated with alcohol use and smoking tobacco. Heartburn is not thought to cause this cancer.
- Following a diagnosis of esophageal cancer, several tests should be ordered: a CT scan of the chest, abdomen and pelvis, basic blood work and labs and possibly an endoscopic ultrasound (EUS) and PET scan. An EUS is able to determine how deep the tumor has invaded into the esophageal wall and a needle biosy can determine if tumor has spread to local lymph nodes. A PET scan is often used to be sure cancer has not spread to any distant locations within the body. Based on the results of the initial CT scan ,more decisions can be made for additional testing. Your doctor should explain all of this to you – its complicated.
- Find a team of doctors and get second opinions. It is not unusual for a patient to see one physician and never see other specialists. This might be ok, but it might not. A good care team would consist of a gastroenterologist, oncologist, radiation oncologist, thoracic surgeon, psychologist, nutrition specialist and possibly a pain specialist and naturopathic doctor. Second opinions are always a good idea, if possible. Why not be sure you are getting the right care? Try to resist the urge to painic and rush into treatment. There is always time to get good opinions before starting a treatment plan. If your gut instinicts tell you a doctor doesnt seem to care about you, move on and find someone who will provide good care. See if you can find doctors with a special interest in your condition.
- Let people in – friends , family, strangers, anyone who cares. This is no time to go it alone. No man is an island. Treatment of esophageal cancer can be a challenge. Let the fear of this disease motivate you to reach out to those around you. Mend broken relationships. reconnect with loved ones. People want to help. You are also going to need support to get through chemotherapy and surgery. Someone who can bring you to office visits and check ups is a great asset.
- After you find a great team and do your research, try not to obsess over the details. Focus on healing, following instructions, and taking care of yourself. Be more spiritual, read books, pray , meditate. Communicate with your medical team early when having problems.
- Last, have a long view of this. This is a marathon not a sprint. Value each day you have and take things one day at a time.
- Support research. Esophageal cancer is a tough disease. Breakthroughs are needed. Find good people who want to cure this disease and support them. Help the next person who may be affected by this cancer. Lets learn form each other.
More Reading and Review
Like all cancers, esophageal cancer has stages – from an early pre-cancer, also known as dysplasia to early cancer meaning the tumor is confined to the esophageal lining. Over time the tumor begins to penetrate deeper into the esophageal wall and may spread into neighboring lymph nodes, and adjacent organs. finally , distant sites such as the liver. so they may understand that anyone who has been diagnosed with esophageal cancer it is important to understand and there are many good resources for further reading and research. There are some important facts that anyone with esophageal cancer should understand. In this post we will try to shed more light on the causes of esophageal cancer, how it is detected, how it can be prevented, and how it is managed.
Who gets esophageal cancer?
Esophageal cancer that arises in the lining of the esophagus and usually goes undetected until it is advanced. Warning symptoms may include difficulty swallowing, pain with swallowing, loss of appetite, weight loss, anemia -blood loss. In the US, esophageal cancer is highly associated with chronic heartburn in white males. Screening for esophageal cancer is recommended in any individual with more than 5 years of regularly occurring heartburn and age >50 yo or any individual with “warning symptoms”. In the United States, over 16,000 individuals are diagnosed with esophageal cancer each year. Worldwide there were over 450, 000 cases based on 2012 studies.
Squamous Cell Cancer
Squamous cell carcinoma — The incidence of esophageal SCC varies considerably among geographic regions. The highest rates are found in Northern Iran, Central Asia, and North-Central China(the so-called “esophageal cancer belt”) [5,18,19]. Geographic variation has also been reported within individual countries [20]. Within China, for example, rates of esophageal cancer range from 1.4 to 140 per 100,000 in the Hebi and Hunyuan counties, respectively [21].
The authors estimated that a history of smoking, alcohol consumption, and diets low in fruits and vegetables accounted for almost 90 percent of esophageal SCC in the United States. The relative importance of specific risk factors may be substantially different in other parts of the world [22]. As noted above, the major risk factors for SCC in the “esophageal cancer belt” of Iran and Asia are not well understood, but are thought to include poor nutritional status, low intake of fruits and vegetables, and drinking beverages at high temperatures
The incidence is higher in urban areas (compared with rural areas) of the United States, particularly among African-American men. In one report, the incidence among African-American men in Washington D.C. was 28.6 per 100,000 [23]. This compares to an overall incidence of approximately 3 to 4 per 100,000 in other parts of the United States.
Smoking and alcohol are also risk factors for other aerodigestive cancers (head and neck and lung), as a result of field cancerization. Head and neck cancers are found in approximately 10 to 15 percent of patients diagnosed with esophageal cancer. In addition, patients with one aerodigestive malignancy have an increased risk of synchronous and second primary tumors of the aerodigestive tract compared with the age-matched general population. (See “Epidemiology and risk factors for head and neck cancer” and“Second primary malignancies in patients with head and neck cancers”.)
The type and quantity of alcoholic beverages consumed may affect the risk of esophageal SCC. Hard liquor may have a higher risk than wine or beer; however, the cumulative amount of alcohol rather than the type is probably more important [32,33]. Individual susceptibility to alcohol may also be involved [34-36]. In one report, for example, variations in the alcohol dehydrogenase genes were protective against aerodigestive cancers [35
Dietary factors — Several dietary associations with esophageal SCC have been uncovered in Asia. Foods containing N-nitroso compounds have long been implicated [37,38]. These compounds are carcinogens that may exert their mutagenic potential by inducing alkyl adducts in DNA [39]. Certain types of pickled vegetables and other food-products consumed in high-risk endemic areas are rich in N-nitroso compounds [40,41]. Toxin-producing fungi (eg, aflatoxin) have also been identified in food sources within endemic areas and may, in part, exert their mutagenic potential by reducing nitrates to nitroso compounds [42].
Chewing of areca nuts or betel quid (areca nuts wrapped in betel leaves), which is widespread in certain regions of Asia, has been implicated in the development of esophageal SCC [43,44]. The mechanism may involve the release of copper, with resulting induction of collagen synthesis by fibroblasts [45].
High temperature beverages and foods may increase the risk of esophageal cancer by causing thermal injury to the esophageal mucosa [46-48]. In a systematic review of 59 studies, more than 50 percent of the studies found that higher temperatures of fluid intake were associated with a statistically significant increase in the risk of esophageal cancer [46]. For coffee and tea, there was little evidence for an association between the amount of use (unrelated to temperature) and esophageal cancer risk. Few studies reported the results for SCC and adenocarcinoma separately. Chemical substances within the beverage likely confound this risk association.
An association with drinking hot tea was noted in a case-control study from northern Iran in which drinking hot tea (60 to 64°C) or very hot tea (≥65°C), and drinking tea within three minutes of its being poured was significantly associated with an increased risk of esophageal SCC [47].
Dietary Factors that Affect the Risk of Esophageal Cancer
Most of these studies come from regions with a high frequency of SCC. These include:
- A positive association between red meat intake and risk of esophageal SCC [49,50].
- Low selenium levels increase risk [51,52], while selenium supplementation has been associated with reduced risk [53-57].
- Zinc deficiency [58], which may act by enhancing the carcinogenic effects of nitrosamines [59-61] and by over-expression of cyclooxygenase (COX)-2 [62].
- An association between low intake of dietary folate and an increased risk of esophageal cancer has been reported [63,64].
- A meta-analysis of observational studies suggested a significant association between higher intake of fruits and vegetables and a reduced risk of esophageal SCC [65].
How is Esophageal Cancer Detected?
This cancer begins along the surface of the esophageal lining. As it grows larger it can invade into local structures and large lymph nodes may develop. In advanced cases, a CT scan or other imaging tests may be able to see the tumor. Ultimately, an upper endoscopy is required to directly visualize the cancer and take samples or biopsies. At the time of endoscopy, the tumor size can be measured and the degree of narrowing noted. Small samples taken during the procedure are sent to a pathologist for further study.The pathologist may perform special stains and tests
Underlying esophageal disease — The presence of specific preexisting esophageal diseases (such as achalasia and caustic strictures) increases the risk of esophageal SCC as illustrated by the following observations:
In a population-based study including 1062 patients with achalasia, the risk of esophageal SCC was increased more than 16-fold during the first 1 to 24 years following diagnosis. Cancer was detected an average of 14 years after the diagnosis of achalasia [66]. (See “Achalasia: Pathogenesis, clinical manifestations, and diagnosis”, section on ‘Natural history and prognosis’.)
In a review of 2414 patients with esophageal SCC, 63 had a history of caustic esophageal injury due to ingestion of lye during childhood. The average time to diagnosis of SCC was 41 years (range 13 to 71 years) following the ingestion [67]. (See “Caustic esophageal injury in adults”, section on ‘Esophageal squamous cell carcinoma’.)
Prior gastrectomy — Patients who have undergone a partial gastrectomy may be at increased risk of esophageal SCC. One series found that 12 of 115 patients with esophageal SCC (10 percent) had undergone a partial gastrectomy [68]. This may represent the co-existence of common risk factors for disorders predisposing to esophageal SCC and the need for partial gastrectomy such as smoking or alcohol. However, another report found that the risk of esophageal SCC and adenocarcinoma was not affected by prior gastric surgery [69].
Atrophic gastritis — Atrophic gastritis and other conditions that cause gastric atrophy are associated with an approximately twofold increased risk of esophageal SCC (but not adenocarcinoma) [70]. (See “Metaplastic (chronic) atrophic gastritis”, section on ‘Esophageal squamous cell carcinoma’.)
Human papillomavirus — Certain infectious agents have been implicated in the pathogenesis of esophageal SCC [71]. Human papillomavirus (HPV, particularly serotypes 16 and 18) has received the most scrutiny. More than 100 studies have investigated the relationship between HPV and esophageal SCC. (See “Human papillomavirus infections: Epidemiology and disease associations”, section on ‘Disease associations’.)
It seems unlikely that HPV represents an important risk factor for esophageal SCC, although certain subtypes may be involved in a small subset of cancers.
Tylosis — Tylosis is a rare disease associated with hyperkeratosis of the palms of the hands and soles of the feet, and a high rate of esophageal SCC (picture 1) [88]. The inherited type of tylosis (Howell-Evans syndrome) has been most strongly linked to esophageal SCC. The disease has an autosomal dominant mode of inheritance; a gene locus has been mapped to chromosome 17q25.1, which probably contains a tumor suppressor gene [89]. Deletions in this gene have also been implicated in sporadic forms of esophageal SCC, occurring in 70 percent of patients with esophageal SCC in one series [89]. (See “Cutaneous manifestations of internal malignancy”.)
A guideline issued by the American Society for Gastrointestinal Endoscopy recommends beginning endoscopic surveillance at age 30 [90]. The time interval of endoscopic surveillance is not yet established. Generally, endoscopic examination should not be conducted more frequently than every one to three years.
Bisphosphonates — Use of oral bisphosphonates has been linked to esophageal adenocarcinoma and SCC in post-marketing surveillance [91]. The finding of crystalline material similar to alendronate in biopsies of patients with drug-related erosive esophagitis, and the persistence of the abnormalities after healing of the esophagitis suggested the potential for carcinogenicity [92,93]. As a result of these observations, the FDA recommended that oral bisphosphonates not be used in patients with Barrett’s esophagus [91].
However, the association between oral bisphosphonates and esophageal cancer was called into question by a cohort study using the United Kingdom General Practice Research Database in which 41,826 members who were treated with oral bisphosphonates between 1996 and 2006 were compared with a one-to-one matched control group (same sex, year of birth, and general practice, regardless of bisphosphonate use) [94]. At a mean follow-up of over four years, there was no difference in the risk of esophageal or gastric cancer combined, or esophageal cancer alone (adjusted hazard ratio [HR] 1.07, 95% CI 0.77-1.49) between the cohorts for any bisphosphonate group.
Upper aerodigestive tract cancer — Several studies have described an association between a current or past history of SCC of the head and neck (ie, oral cavity, oropharynx, hypopharynx, or larynx), lung or esophagus with synchronous or metachronous SCC of the esophagus [90,95-102]. This probably reflects similar risk factors such as smoking or alcohol. In prospective studies of men with head and neck cancer, the incidence of synchronous or metachronous esophageal cancer has range from 3 to 14 percent [97-100,102,103]. Metachronous lesions appeared at varying time intervals and there is no clear decrease in risk with time.
These observations have led some authorities to recommend periodic screening endoscopy but the benefits of such an approach have not been established. A guideline issued by the American Society of Gastrointestinal Endoscopy recommends that there are insufficient data to support routine endoscopic surveillance for patients with previous aerodigestive SCC [90]. However, a single endoscopy may be indicated to identify synchronous esophageal cancer.
Cancer Types
There are two major cancer types in the esophagus:
- Adenocarcinoma
- Squamous
Most patients present to their family doctor or internist and then referred to a gastroenterologist (GI doctor) – a specialist in managing gastrointestinal conditions. The GI physician will usually perform an upper endoscopy to the esophagus directly.
90% of esophageal cancer cases in the US are either classified as either adenocarcinoma or squamous cell carcinoma. Worldwide, squamous cancer is more common, but in Western countries, adenocarcinoma predominates.
50-60% of patients discovered to have esophageal cancers are incurable.
Of patients with T3 disease or node positive, only 15% are alive at 5 years.
Imaging studies can detect esophageal cancer such as a barium swallow of CT scan.
However, biopsies or samples of the tumor must be obtained to confirm a diagnosis of cancer. This is usually achieved with an upper endoscopy and several samples taken for analysis in the laboratory
Staging of Esophageal Cancer
Staging of a cancer looks at three factors – how deep the tumor has penetrated into the wall of the esophagus, if tumor has spread into local lymph nodes, and if tumor has spread into other organs.
The symbols TNM are used when staging cancer and represent each of the factor listed
T= tumor depth of penetration
N= lymph nodes involved
M= metastasis (tumor has spread to other organs)
In order to obtain the T N M stage, a battery of tests must be ordered and usually include:
CT scan
Endoscopic Ultrasound
PET scan
These tests are able to determine if the tumor is confined to a single location, have spread to neighboring lymph nodes or into other regions of the body.
Treatment of the cancer will depend on the final stage provided by the TNM score
More about the TNM Criteria
Staging Squamous Tumors
The most widely used standard for staging cancers is provided by the AJCC (American Joint Committee on Cancer). Their most recent guidelines adopted in 2010 are as follows
T stage – the T stage can range from 0 to 4. Here are the individual T stages
T Stages
T0 – this means the tumor cannot be detected on the imaging test or on biospy. This might be an individual who had a previous positive biopsy of the esophagus, but the cancer was so early it can’t be seen on the CT scan or EUS exam
Tis – high grade dysplasia is found on biopsy. This is technically not a cancer, but a pre-cancer. A tumor with Tis stage could potentially be removed using the endoscope only without surgical intervention
T1 – Superficial Layers
T1a – tumor involves lamina propria. This tumor could potentially be removed through endoscopy alone rather than surgery
T1b – tumor has penetrated into submucosa. These tumors should be removed surgically if possible
T2 – tumor has penetrated into the muscular wall later – also known as muscularis propria.
T3 – tumor has penetrated through muscular wall of esophagus to outer wall layer
T4 – tumor is invading adjacent structures
T4a – tumor involves the pleura, pericardium or diaphragm and could be surgically removed
T4b –tumor involves the trachea, spine, aorta. Can not be removed surgically
Nodal Status
N0 – no nodes involved with cancer
N1 – 1-2 regional lymph nodes are involved
N2 – 3 to 6 regional lymph nodes are involved
N3 – 7 or more regional lymph nodes involved
M Status
M0 – no metastasis
M1 – there is spread of tumor to an organ outside of the esophagus
G Status
This is the tumor grade or the degree of abnormality with the tumor is examined under the microscope. The G status may range from G1- 4. The more irregular and distorted the higher the G score. Generally speaking, a G1 tumor may be less aggressive than a G3 tumor.
G1 – well differentiated tumor
G2 – moderately differentiated
G3 – poorly differentiated
G4 – undifferentiated
Putting it all Together
The Accurate Stages
You should be sure that all necessary tests have been performed in order to determine the T N and M stages and the G stage. This means you will have a reports from the CT scan, PET scan, Endoscopic ultrasound, and the pathologist. An accurate stage can now be given.
Stage 0 – this is a Tis N0 Mo Grade 1 – this means high grade dysplasia is present, no lymph nodes and no spread to other organs. The microscopic exam of the esophageal sample does not appear too abnormal – it still resembles a normal cellular pattern
Stage 1 – there are two categories.
- Stage 1A – T1 No Mo G1-2 this means the tumor is no deeper than the submucosa, no lymph nodes are involved and no metastasis. The G status shows mild to moderate disorganization of cellular structure but not extreme derangement
- Stage IB – T1 N0 M0 G3 or T2N0M0 G1-2
- For T1N0M0 G3 – this means the tumor penetrates no deeper than the submucosa, no lymph nodes are present , no metastasis but the G status is more advanced – cellular structure is very abnormal
For T2N0M0 G1-2 – the tumor penetrates into the muscular layer of the esophageal wall, no lymph nodes are involved, no metastasis. The G status shows mild to moderately abnormal appearing cells on microscopic exam
Stage II – there are two categories.
Stage II A – T2NOM0 G3 – this tumor has penetrated into the muscular wall layer, no lymph nodes are involved and cells are very distorted when viewed under the microscope
Stage IIB – T3N0M0 any G or T1-2 N1 M0 any G
- T3N0M0 any G – this indicates the tumor has penetrated through the outer wall of the esophagus, no lymph nodes are involved and no metastasis. The G status is not important
- T1-2 N1 M0 any G – the tumor is still confined to the muscular layer, N1 means cancer has spread to 1 or 2 regional lymph nodes , no metastasis and the G status is not important
Stage III – there are 3 categories – IIIA, IIIB, and IIIC
- IIIA – T1-2 N2 M0, any G
- T3 N1 M0
- T4a N0 M0
- IIIB – T3N2 M0, any G
- IIIC – T4a N1-2 M0, any G
- T4b any N , N0 M0 any G
- Any T N3 M0
Stage IV
Any T, Any N, M1 – this means that is spread of tumor to other organs, the stage is automatically a IV (4). It doesn’t matter what the T or N stage is at that point.
Lymph Nodes Important to Esophageal Cancer Staging
- 1R: Right lower cervical paratracheal nodes, between the supraclavicular paratracheal space and apex of the lung.
- 1L: Left lower cervical paratracheal nodes, between the supraclavicular paratracheal space and apex of the lung.
- 2R: Right upper paratracheal nodes, between the intersection of the caudal margin of the brachiocephalic artery with the trachea and the apex of the lung.
- 2L: Left upper paratracheal nodes, between the top of the aortic arch and the apex of the lung.
- 4R: Right lower paratracheal nodes, between the intersection of the caudal margin of the brachiocephalic artery with the trachea and cephalic border of the azygos vein.
- 4L: Left lower paratracheal nodes, between the top of the aortic arch and the carina.
- 7: Subcarinal nodes, caudal to the carina of the trachea.
- 8U: Upper thoracic paraesophageal lymph nodes, from the apex of the lung to the tracheal bifurcation.
- 8M: Middle thoracic paraesophageal lymph nodes, from the tracheal bifurcation to the caudal margin of the inferior pulmonary vein.
- 8Lo: Lower thoracic paraesophageal lymph nodes, from the caudal margin of the inferior pulmonary vein to the EGJ.
- 9R: Pulmonary ligament nodes, within the right inferior pulmonary ligament.
- 9L: Pulmonary ligament nodes, within the left inferior pulmonary ligament.
- 15: Diaphragmatic nodes, lying on the dome of the diaphragm and adjacent or to behind its crura.
- 16: Paracardial nodes, immediately adjacent to the gastroesophageal junction.
- 17: Left gastric nodes, along the course of the left gastric artery.
- 18: Common hepatic nodes, immediately on the proximal common hepatic artery.
- 19: Splenic nodes, immediately on the proximal common hepatic artery.
- 20: Celiac nodes, at the base of the celiac artery.
Dr William D. Lyday,
Gastroenterologist
Gastroenterology Atlanta
Our Specialty Services:
Heartburn – IBS – Weight Management
Nutritional Counseling – Colonoscopy
Cancer Screening – Genomic DNA Testing
Call us today to request an online virtual consultation or checkup with Dr. Lyday. We offer comprehensive medical evaluations from the comfort of your own home, including complete examinations, ordering of all tests, X-Rays & labs and prescriptions.
Call us at or click here to schedule your virtual appointment or office visit.
Dr William D. Lyday,
Gastroenterologist
Gastroenterology Atlanta
Our Specialty Services:
IBS
Heartburn
Colonoscopy
Cancer Prevention
Weight Management
Nutritional Counseling
Genomic DNA Testing
Call us today to request an online virtual consultation or checkup with Dr. Lyday. We offer comprehensive medical evaluations from the comfort of your own home, including complete examinations, ordering of all tests, X-Rays & labs and prescriptions.
Call us at or click here to schedule your virtual appointment or office visit.