Esophageal Cancer: Overview of Risk Factors, Diagnosis and Management

Esophageal CancerEsophageal Cancer
Written by: Krystie Linares
Krystie Linares is a physician with 10 years of experience as a family practitioner and occupational health specialist. She has collaborated with several companies, startups, and individuals, by doing research, developing educational content, managing medical libraries, and working as a database curator.
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Esophageal Cancer: Overview of Risk Factors, Diagnosis, and Management

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Summary

Several forms of esophageal cancer can occur; the most common subtype around the world is squamous cell carcinoma (SCC), while adenocarcinoma (AC) is the most frequent subtype found in the Western world. SCC arises in the squamous epithelial lining of the esophagus due to dysplasia caused by inflammatory changes, while AC usually originates in the columnar glandular metaplastic cells that replace the squamous epithelium, and it is a consequence of Barrett’s esophagus.

Esophageal cancer has become the sixth cause of cancer-related deaths in the world and has an overall poor survival rate. Risk factors for esophageal cancer include GERD, Barrett’s esophagus, obesity, male gender, advanced age, smoking, alcohol consumption, and a poor diet. An adequate intake of fruits, vegetables, and fiber has been shown to protect against the disease. The standard treatment for all stages of esophageal cancer is esophagectomy; however, other treatment options have been sought to decrease the high rates of morbidity and mortality associated with this surgery.

Physiopathology of Esophageal Cancer

Esophageal cancer can occur in several forms, the most common subtypes are squamous cell carcinoma (SCC) and adenocarcinoma (AC), but other rare and less common subtypes include small cell carcinomas, sarcomas, melanomas, leiomyosarcomas, and lymphomas. (1-4)

Tumorigenesis of esophageal cancer differs significantly depending on the type of affected cell. For instance, SCC originates in the stratified squamous epithelial lining of the esophagus due to dysplasia caused by undergoing inflammatory changes, which ultimately leads to in situ malignant changes. Therefore, SCC often occurs in the cervical, upper thoracic, or middle thoracic portions of the esophagus. While AC usually originates in the columnar glandular metaplastic cells that replace the squamous epithelium, which is mainly found in the lower thoracic portion of the esophagus. This is commonly known as Barrett’s esophagus. Additionally, AC occurring in the gastroesophageal (GE) junction is typically also classified as esophageal cancer. (2, 5)

Epidemiology of Esophageal Cancer

Esophageal cancer is the seventh most common type of cancer worldwide, with approximately 604,000 new cases per year, and due to its aggressiveness and often late diagnosis, it has become the sixth cause of cancer-related deaths in the world, having a poor survival rate of around 15 to 25% at 5 years after diagnosis. (6-10)

The majority of cases of esophageal cancer worldwide are due to SCC. However, AC is most frequent in the Western world, including the United States and Western Europe, probably related to the increase in risk factors associated with Barrett’s esophagus. (11-14)

Nevertheless, esophageal cancers are still relatively infrequent in the United States. (15-17)

Risk Factors

Gastroesophageal Reflux Disease (GERD)

Although GERD does not represent a risk factor for esophageal cancer by itself, it has been demonstrated that it can damage the lining of the esophagus, which in turn increases the risk of developing Barrett’s esophagus, which can eventually lead to AC of the esophagus. Patients who experience weekly symptoms of GERD have a five-fold risk of developing esophageal cancer, whereas patients who experience daily symptoms of GERD have their odds increased by sevenfold. (18-21)

Barrett’s Esophagus

Barrett’s esophagus happens in approximately 6% to 14% of patients with long-term untreated GERD, and it is characterized by mucosal dysplasia that extends proximally from the GE junction into the normal mucosa of the esophagus. (18-20, 22)

It has been identified an increased risk of 50 to 100 times suffering from AC in the context of Barret’s esophagus (4). However, despite this significant increase in risk, most patients do not develop cancer of the esophagus, and the overall risk of AC among patients with Barrett’s esophagus has been reported to be around 0.5% to 1%. (22)

Obesity

A high body mass index (BMI) has been linked to an increased risk of esophageal cancer, especially AC. Patients with a BMI of 30 or more have a 16-fold risk of developing esophageal cancer when compared to patients with a BMI of 22 or less. Furthermore, an increased waist circumference is an independent risk factor for esophageal cancer, despite BMI. (23, 24)

Although it has not yet been precisely elucidated why obesity and an increased waist circumference are risk factors for developing esophageal cancer, suggested explanations include that an elevated intra-abdominal pressure due to obesity can lead to gastroesophageal reflux and esophagitis, which increases the risk of Barrett’s esophagus and subsequent AC. Additionally, obesity can also cause hormonal imbalances that have carcinogenic effects.

Gender

Since males tend to have a greater waist circumference than females, and knowing that obesity and an increased waist circumference are independent risk factors for esophageal cancer, this may explain why men have a 2-fold to 3-fold risk of developing esophageal cancer when compared to women, especially in the AC histologic type. (10, 18, 22, 25)

Age

The incidence of esophageal cancer is highest in patients who are in their sixth and seventh decades of life. As age increases, the likelihood of developing this disease also increases significantly, with patients older than 65 years being approximately 20 times more prone than those below that age. Diagnosis of esophageal cancer occurs at a median age of 68 years. (22)

Smoking and Alcohol Consumption

Tobacco and alcohol intake are two of the leading causes of esophagus cancer, especially SCC. There is a direct correlation between esophageal cancer and the weekly volume of alcohol ingested per week. On the other side, tobacco increases the risk of esophageal cancer due to the number of carcinogens, particularly nitrosamines, that come into contact with the esophageal mucosa when smoking. There is also a strong direct correlation between the number of cigarettes smoked per day and the length of time a patient has been smoking, with the risk of developing esophageal cancer. (22, 26-28)

Poor Diet

A diet rich in fruits, vegetables, and fiber has been shown to protect against the development of esophageal cancer. (22)

However, frequent consumption of foods rich in nitrogenous compounds, like pickled vegetables, and very hot beverages like coffee, tea, and especially mate, have been linked to the development of the disease. (22, 29, 30)

Tylosis

Tylosis is a rare autosomal dominant syndrome caused by a gene mutation in chromosome 17q25. This syndrome has been strongly linked to an increased lifetime risk of developing esophageal SCC (approximately 40% to 90% by 70 years of age), and it is characterized by hyperkeratosis of the palms and soles and oral precursor lesions. (22, 31, 32)

Signs and Symptoms of Esophageal Cancer

Patients with esophageal cancer are usually asymptomatic in the early stages of the disease, whereas patients with advanced disease may present with progressive dysphagia (first solids and then liquids), unintentional weight loss, odynophagia, new-onset dyspepsia, chest pain, and less commonly hoarseness, cervical adenopathy, and signs of blood loss. (33-35).

Diagnosis

The initial diagnostic evaluation in these patients should be upper endoscopy and biopsy. Once the diagnosis of esophageal cancer has been confirmed, clinical staging should be performed using imaging techniques such as computed tomography (CT) and positron-emission tomography (PET). (33-38)

CT scanning

Abdominal and chest CT scans are useful to help exclude the presence of metastases and to help determine if the tumor has invaded adjacent structures. (39)

PET scanning

Positron emission tomography is useful to detect occult distant lymph node metastases and bone spread, thus, aiding with staging. (40)

Endoscopic ultrasound

Endoscopic ultrasound (EUS) is a useful test that can help determine the depth of tumor penetration and the presence of peri-esophageal nodal disease. When used along with fine needle aspiration (FNA) biopsy, EUS can be significantly more accurate in evaluating lymph node metastasis. (41, 42)

Bronchoscopy

Bronchoscopy can be used to help exclude invasion of the trachea or bronchi in patients with cancer of the middle and upper third of the thoracic esophagus only in the absence of M1 disease.

Treatment

Treatment of esophageal cancer varies according to the stage and histologic subtype. According to the National Comprehensive Cancer Network (NCCN) Guidelines, esophagectomy is the mainstay of treatment for all stages of esophageal cancer; however, it is a very invasive and challenging surgery that is associated with a high incidence of morbidity and mortality. Furthermore, symptoms derived from the surgery, such as hyporexia, dysphagia, reflux, and early satiety, can decrease the quality of life of the patient. (43-45)

Therefore, other treatment modalities are available for patients who are unwilling or unable to go through esophagectomy and for those patients with early esophageal cancer. These treatments include:

  • Endoscopic submucosal dissection;
  • Endoscopic mucosal resection;
  • Photodynamic therapy;
  • Radiofrequency ablation.

Furthermore, over the last few years important progress has been made in esophagectomy with the introduction of minimally invasive esophagectomy (MIE), which allows for the length reduction of the surgical incision and minimizes postoperative morbidity and mortality by using thoracoscopy and laparoscopy for the thoracic and abdominal stages of the procedure. (46)

Unfortunately, esophageal cancer is usually diagnosed at an advanced stage when the patient presents with symptoms such as dysphagia. In these cases, the disease is already at T2 or T3; therefore, a cure cannot be achieved with surgery alone. (47, 48)

Prevention

In the Western world, screening for esophageal cancer is not feasible and neither cost-effective due to the relatively low incidence of the disease and the lack of early symptomatology. However, some preventive measures can be taken to decrease the overall risk of esophageal cancer: (1, 49)

Squamous Cell Carcinoma

  • Smoking cessation;
  • Reducing alcohol intake;
  • Eating a diet rich in fruits, vegetables, and fiber.

 Esophageal Adenocarcinoma

Prevention should be aimed at controlling GERD to prevent the development of Barrett’s esophagus and subsequent metaplasia to high-grade dysplasia cascade. In these patients, endoscopic follow-up evaluations should be performed periodically to allow for the early detection of dysplasia, allowing appropriate intervention before cancer develops.

Disclosures

The author does not report any conflict of interest

Disclaimer

This information is for educational purposes, not to treat disease or supplant professional medical judgment. Physicians should follow local policy regarding the diagnosis and management of medical conditions.

See Also

Malabsorption Syndrome

Peptic Ulcer Disease

Acute Diarrhea in Adults

Acute Abdomen

Overview of Lung Cancer

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