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Esophageal Carcinoma

Updated : May 14, 2024





Background

Most esophageal cancers are histologically classified as either adenocarcinoma or squamous cell carcinoma. Over the past 30 years, the incidence rate of adenocarcinoma has increased by 60%, and the incidence rate of squamous cell carcinoma has decreased by 30% in the U.S.

When the incidence of adenocarcinoma of the distal esophagus and gastroesophageal junction (GEJ) is stratified by anatomic site, the incidence continues to rise significantly due to Barrett’s esophagus.

Epidemiology

Esophageal cancer is the sixth most common cancer in the world and fifth most prevalent cancer, with around 16,940 cases reported annually. The regions with the highest risk of esophageal cancer incidence include southern Russia, countries in Central Asia, Northern China, and some parts of northern Iran. 90% of cases in this “esophageal cancer belt” are because of squamous cell cancers.

In comparison, the United States is considered a low-risk area, with an increase in the incidence of esophageal adenocarcinoma owing to an increase in obesity and GERD, but a consistent decline in squamous cell carcinoma due to long-term cigarette and alcohol use reductions. Adenocarcinoma is a disease that primarily affects white, male men. On the other hand, the incidence of esophageal squamous cell carcinoma is higher among blacks and Asians.

Anatomy

Pathophysiology

Esophageal squamous cell carcinoma is characterized by tiny polypoid excrescences, denuded epithelium, and plaques that are most frequently found in the esophagus’s midsection. To aid in diagnosis, tissue staining with Lugol’s iodine should be utilized to differentiate normal squamous epithelium containing glycogen from malignant squamous glycogen-deprived cells.

Advance lesions are ulcerated and circumferential in nature, infiltrate the submucosa, and expand cephalad. Although lymphatic spread to regional lymph nodes occurs in about a third of patients, distant metastases to the liver, lung, and bone, including invasion of malignant cells into the bone marrow, occur in about a third of patients.

Around 60% of distal esophageal adenocarcinoma and, more commonly, GEJ cases develop from Barrett’s esophagus metaplastic epithelium. Typically, patients with Barrett’s esophagus are monitored via upper endoscopy and biopsy to look for indications of dysplasia. Adenocarcinoma has an incidence rate of 1.0 case per 1000 person-years in patients without dysplasia, however, discovery of low-grade dysplasia on the index endoscopy had an incidence rate of 5.1 cases per 1000 person-years.

The risk of developing esophageal cancer is 0.12 percent per year. High-grade dysplasia should be treated aggressively, including surgical excision as a possibility. Early metastases develop in lymph nodes adjacent to or regional to the primary site. Predictors such as tumor markers (TP53) may signal the possibility of the illness becoming malignant.

The human epidermal growth factor receptor 2 (HER2) gene and protein expression have been linked to tumor invasion and lymph node metastasis, both of which are associated with a poorer prognosis. HER2 is overexpressed at a higher rate (30%) in adenocarcinoma than in squamous cell carcinoma (13%). All metastatic adenocarcinomas should be evaluated for HER2, initially using an immunohistochemical score (negative for 0 or 1+ and positive for 3+, with reflex FISH for 2+).

Etiology

In the United States, a history of smoking, alcohol drinking, and a diet deficient in fruits and vegetables accounts for about 90% of esophageal squamous cell carcinoma cases. In poorer nations, risk factors for esophageal squamous cell carcinoma are less definite, but they do exist. Most of these risk factors are associated with poor nutrition, and an insufficient intake of vegetables and fruits.

Individuals infected with human papillomavirus experience higher incidence rates of upper esophageal squamous cell carcinoma. Achalasia, caustic strictures, gastrectomy, and atrophic gastritis are all linked to a higher incidence of esophageal squamous cell carcinoma. Current or prior squamous cell carcinoma of the aerodigestive tract could be linked with synchronous or metachronous esophageal squamous cell carcinoma.

A rare autosomal condition called Tylosis which is linked with Howel-evans syndrome is also strongly connected with esophageal squamous cell carcinoma and presents a 40%-90% chance of acquiring cancer by 70 years of age. The TEC gene is present on chromosome 17q25 and it is also been linked to sporadic squamous cell carcinoma.

In the US, most esophageal adenocarcinomas are caused by Barrett’s metaplasia, for which risk factors include history of chronic smoking, a high BMI, gastroesophageal reflux disease, and low fruit and vegetable intake. Barrett’s esophagus metaplasia is responsible for several conditions which are responsible for increasing esophageal acid exposure in the body. These include:

  • Sclerodoma
  • Medications which relax the lower esophageal sphincter
  • Zollinger-Ellison Syndrome
  • Certain medical procedures

Rare autosomal dominant susceptible alleles are mostly responsible for causing Familial Barrett’s esophagus. Patients with esophageal adenocarcinomas are also susceptible for the same, especially if white-skinned and over 40 years old. No interventions can prevent the onset of Familial Barrett’s esophagus, but some are known to curb the progression of the condition. Some of these are:

  • Vitamin C consumption
  • Folate consumption
  • Non-steroidal anti-inflammatory drugs
  • Proton-pump inhibitors
  • A diet high in cereal
  • Antioxidants

Genetics

Very few esophageal cancers develop due to inherited gene mutations. Four of the DNA changes and their effects on cellular growth have been studied in detail. These are:

  • Bloom syndrome- It is the result of mutations in the BLM gene. The BLM gene is required to produce a protein that stabilizes DNA during cell division. Without this protein, DNA can become damaged, potentially resulting in cancer. Bloom syndrome patients are at an increased risk of developing squamous cell esophageal cancer, as well as AML, ALL, and other lymphatic system cancers. Typically, a defective gene for this disease is inherited from both parents.
  • Howel-Evans syndrome or tylosis with esophageal cancer- This syndrome is caused because of inherited mutations in the RHBDF2 gene. Individuals with mutations in this gene are more prone to developing esophageal squamous cell carcinoma.
  • Familial Barrett’s Esophagus: This is a syndrome which is commonly noticed in families suffering from adenocarcinoma of the GE junction and the esophagus, and from Barrrett’s esophagus. Research is still being conducted to identify the exact genes which cause this illness.
  • Fanconi anemia: Fanconi anemia is a rare genetic disorder characterized by defective genes that are incapable of repairing damaged DNA. Mutations in various FANC genes can increase the chance of developing a variety of malignancies, including AML and esophageal squamous cell carcinoma.

In contrast to inherited gene mutations, acquired gene mutations are responsible for most cases of esophageal cancers. It is assumed that alcohol and tobacco use is connected to these mutations, but for now, what causes them is still a mystery.

Prognostic factors

The prognosis of esophageal cancer is dependent on a few factors such as:

  • The location of the tumor
  • The extent of its spread
  • The extent of surgical excision of the tumor

Greater extent of spread is associated with a poorer prognosis. On average, the 5-year survival rate for this condition is 20%, but it can range between 5%-47% based on the factors mentioned above.

Prognostic Factors

Clinical History

Physical Examination

Age group

Associated comorbidity

Associated activity

Acuity of presentation

Differential Diagnoses

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

Medication

 

tislelizumab (Pending FDA Approval) 

FDA approval is pending for unresectable recurrent locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) in persons who have previously had systemic therapy



 
 

Media Gallary

References

https://www.cancer.org/cancer/esophagus-cancer/causes-risks-prevention/what-causes.html

https://www.ncbi.nlm.nih.gov/books/NBK459267/

Esophageal Carcinoma

Updated : May 14, 2024




Most esophageal cancers are histologically classified as either adenocarcinoma or squamous cell carcinoma. Over the past 30 years, the incidence rate of adenocarcinoma has increased by 60%, and the incidence rate of squamous cell carcinoma has decreased by 30% in the U.S.

When the incidence of adenocarcinoma of the distal esophagus and gastroesophageal junction (GEJ) is stratified by anatomic site, the incidence continues to rise significantly due to Barrett’s esophagus.

Esophageal cancer is the sixth most common cancer in the world and fifth most prevalent cancer, with around 16,940 cases reported annually. The regions with the highest risk of esophageal cancer incidence include southern Russia, countries in Central Asia, Northern China, and some parts of northern Iran. 90% of cases in this “esophageal cancer belt” are because of squamous cell cancers.

In comparison, the United States is considered a low-risk area, with an increase in the incidence of esophageal adenocarcinoma owing to an increase in obesity and GERD, but a consistent decline in squamous cell carcinoma due to long-term cigarette and alcohol use reductions. Adenocarcinoma is a disease that primarily affects white, male men. On the other hand, the incidence of esophageal squamous cell carcinoma is higher among blacks and Asians.

Esophageal squamous cell carcinoma is characterized by tiny polypoid excrescences, denuded epithelium, and plaques that are most frequently found in the esophagus’s midsection. To aid in diagnosis, tissue staining with Lugol’s iodine should be utilized to differentiate normal squamous epithelium containing glycogen from malignant squamous glycogen-deprived cells.

Advance lesions are ulcerated and circumferential in nature, infiltrate the submucosa, and expand cephalad. Although lymphatic spread to regional lymph nodes occurs in about a third of patients, distant metastases to the liver, lung, and bone, including invasion of malignant cells into the bone marrow, occur in about a third of patients.

Around 60% of distal esophageal adenocarcinoma and, more commonly, GEJ cases develop from Barrett’s esophagus metaplastic epithelium. Typically, patients with Barrett’s esophagus are monitored via upper endoscopy and biopsy to look for indications of dysplasia. Adenocarcinoma has an incidence rate of 1.0 case per 1000 person-years in patients without dysplasia, however, discovery of low-grade dysplasia on the index endoscopy had an incidence rate of 5.1 cases per 1000 person-years.

The risk of developing esophageal cancer is 0.12 percent per year. High-grade dysplasia should be treated aggressively, including surgical excision as a possibility. Early metastases develop in lymph nodes adjacent to or regional to the primary site. Predictors such as tumor markers (TP53) may signal the possibility of the illness becoming malignant.

The human epidermal growth factor receptor 2 (HER2) gene and protein expression have been linked to tumor invasion and lymph node metastasis, both of which are associated with a poorer prognosis. HER2 is overexpressed at a higher rate (30%) in adenocarcinoma than in squamous cell carcinoma (13%). All metastatic adenocarcinomas should be evaluated for HER2, initially using an immunohistochemical score (negative for 0 or 1+ and positive for 3+, with reflex FISH for 2+).

In the United States, a history of smoking, alcohol drinking, and a diet deficient in fruits and vegetables accounts for about 90% of esophageal squamous cell carcinoma cases. In poorer nations, risk factors for esophageal squamous cell carcinoma are less definite, but they do exist. Most of these risk factors are associated with poor nutrition, and an insufficient intake of vegetables and fruits.

Individuals infected with human papillomavirus experience higher incidence rates of upper esophageal squamous cell carcinoma. Achalasia, caustic strictures, gastrectomy, and atrophic gastritis are all linked to a higher incidence of esophageal squamous cell carcinoma. Current or prior squamous cell carcinoma of the aerodigestive tract could be linked with synchronous or metachronous esophageal squamous cell carcinoma.

A rare autosomal condition called Tylosis which is linked with Howel-evans syndrome is also strongly connected with esophageal squamous cell carcinoma and presents a 40%-90% chance of acquiring cancer by 70 years of age. The TEC gene is present on chromosome 17q25 and it is also been linked to sporadic squamous cell carcinoma.

In the US, most esophageal adenocarcinomas are caused by Barrett’s metaplasia, for which risk factors include history of chronic smoking, a high BMI, gastroesophageal reflux disease, and low fruit and vegetable intake. Barrett’s esophagus metaplasia is responsible for several conditions which are responsible for increasing esophageal acid exposure in the body. These include:

  • Sclerodoma
  • Medications which relax the lower esophageal sphincter
  • Zollinger-Ellison Syndrome
  • Certain medical procedures

Rare autosomal dominant susceptible alleles are mostly responsible for causing Familial Barrett’s esophagus. Patients with esophageal adenocarcinomas are also susceptible for the same, especially if white-skinned and over 40 years old. No interventions can prevent the onset of Familial Barrett’s esophagus, but some are known to curb the progression of the condition. Some of these are:

  • Vitamin C consumption
  • Folate consumption
  • Non-steroidal anti-inflammatory drugs
  • Proton-pump inhibitors
  • A diet high in cereal
  • Antioxidants

Very few esophageal cancers develop due to inherited gene mutations. Four of the DNA changes and their effects on cellular growth have been studied in detail. These are:

  • Bloom syndrome- It is the result of mutations in the BLM gene. The BLM gene is required to produce a protein that stabilizes DNA during cell division. Without this protein, DNA can become damaged, potentially resulting in cancer. Bloom syndrome patients are at an increased risk of developing squamous cell esophageal cancer, as well as AML, ALL, and other lymphatic system cancers. Typically, a defective gene for this disease is inherited from both parents.
  • Howel-Evans syndrome or tylosis with esophageal cancer- This syndrome is caused because of inherited mutations in the RHBDF2 gene. Individuals with mutations in this gene are more prone to developing esophageal squamous cell carcinoma.
  • Familial Barrett’s Esophagus: This is a syndrome which is commonly noticed in families suffering from adenocarcinoma of the GE junction and the esophagus, and from Barrrett’s esophagus. Research is still being conducted to identify the exact genes which cause this illness.
  • Fanconi anemia: Fanconi anemia is a rare genetic disorder characterized by defective genes that are incapable of repairing damaged DNA. Mutations in various FANC genes can increase the chance of developing a variety of malignancies, including AML and esophageal squamous cell carcinoma.

In contrast to inherited gene mutations, acquired gene mutations are responsible for most cases of esophageal cancers. It is assumed that alcohol and tobacco use is connected to these mutations, but for now, what causes them is still a mystery.

Prognostic factors

The prognosis of esophageal cancer is dependent on a few factors such as:

  • The location of the tumor
  • The extent of its spread
  • The extent of surgical excision of the tumor

Greater extent of spread is associated with a poorer prognosis. On average, the 5-year survival rate for this condition is 20%, but it can range between 5%-47% based on the factors mentioned above.

tislelizumab (Pending FDA Approval) 

FDA approval is pending for unresectable recurrent locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) in persons who have previously had systemic therapy



https://www.cancer.org/cancer/esophagus-cancer/causes-risks-prevention/what-causes.html

https://www.ncbi.nlm.nih.gov/books/NBK459267/