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Esophageal Cancer

Esophageal Cancer

Esophageal cancer is 1 of the most common causes of cancer-related deaths worldwide. Nearly all esophageal cancers are either adenocarcinoma (commonly affecting the distal esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy) or squamous cell carcinoma Squamous cell carcinoma Cutaneous squamous cell carcinoma (cSCC) is caused by malignant proliferation of atypical keratinocytes. This condition is the 2nd most common skin malignancy and usually affects sun-exposed areas of fair-skinned patients. The cancer presents as a firm, erythematous, keratotic plaque or papule. Squamous Cell Carcinoma (SCC) (affecting the proximal two-thirds of the esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy). Major risk factors for adenocarcinoma include smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases, obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity, and Barrett’s esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy. For squamous cell carcinoma Squamous cell carcinoma Cutaneous squamous cell carcinoma (cSCC) is caused by malignant proliferation of atypical keratinocytes. This condition is the 2nd most common skin malignancy and usually affects sun-exposed areas of fair-skinned patients. The cancer presents as a firm, erythematous, keratotic plaque or papule. Squamous Cell Carcinoma (SCC), risk factors include smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases, alcohol consumption, and certain dietary factors. Early-stage cancer is often asymptomatic, with dysphagia Dysphagia Dysphagia is the subjective sensation of difficulty swallowing. Symptoms can range from a complete inability to swallow, to the sensation of solids or liquids becoming "stuck." Dysphagia is classified as either oropharyngeal or esophageal, with esophageal dysphagia having 2 sub-types: functional and mechanical. Dysphagia and weight loss Weight loss Decrease in existing body weight. Bariatric Surgery presenting as the disease progresses. Diagnosis is by endoscopic biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma or image-guided biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma of the metastatic site. Management depends on the disease stage. Options include surgical resection, chemotherapy Chemotherapy Osteosarcoma, and radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma. For unresectable esophageal cancers, palliative measures are provided for symptom relief and to prolong survival.

Last updated: 24 Aug, 2021

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Contents

Epidemiology and Etiology

Epidemiology

  • 8th-most common cancer worldwide and 6th-most common cause of cancer-related deaths
  • Risk increases with age, especially during the 6th to 7th decades of life
  • Males > females
  • Majority of cases fall under 2 types:
    • Adenocarcinoma (AC)
      • Most common form in the United States
      • Higher incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency in Caucasians
    • Squamous cell carcinoma Squamous cell carcinoma Cutaneous squamous cell carcinoma (cSCC) is caused by malignant proliferation of atypical keratinocytes. This condition is the 2nd most common skin malignancy and usually affects sun-exposed areas of fair-skinned patients. The cancer presents as a firm, erythematous, keratotic plaque or papule. Squamous Cell Carcinoma (SCC) (SCC)
      • Most common form worldwide
      • 90% of esophageal cancers occur in the “esophageal cancer belt” (northern Iran, northern China, Central Asia ASIA Spinal Cord Injuries, and southern Russia)
      • Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency decreasing in the United States
      • Higher incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency in African Americans and Asians

Etiology

  • Risk factors for adenocarcinoma:
    • Barrett’s esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy secondary to gastroesophageal reflux disease Gastroesophageal Reflux Disease Gastroesophageal reflux disease (GERD) occurs when the stomach acid frequently flows back into the esophagus. This backwash (acid reflux) can irritate the lining of the esophagus, causing symptoms such as retrosternal burning pain (heartburn). Gastroesophageal Reflux Disease (GERD) ( GERD GERD Gastroesophageal reflux disease (GERD) occurs when the stomach acid frequently flows back into the esophagus. This backwash (acid reflux) can irritate the lining of the esophagus, causing symptoms such as retrosternal burning pain (heartburn). Gastroesophageal Reflux Disease (GERD))
    • Obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity
    • Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases
  • Risk factors for squamous cell carcinoma Squamous cell carcinoma Cutaneous squamous cell carcinoma (cSCC) is caused by malignant proliferation of atypical keratinocytes. This condition is the 2nd most common skin malignancy and usually affects sun-exposed areas of fair-skinned patients. The cancer presents as a firm, erythematous, keratotic plaque or papule. Squamous Cell Carcinoma (SCC) (SCC):
    • Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases
    • Alcohol intake
    • Diet low in vegetables and fruits
    • Achalasia Achalasia Achalasia is a primary esophageal motility disorder that develops from the degeneration of the myenteric plexus. This condition results in impaired lower esophageal sphincter relaxation and absence of normal esophageal peristalsis. Patients typically present with dysphagia to solids and liquids along with regurgitation. Achalasia
    • Caustic injuries
    • Human papillomavirus Human papillomavirus Human papillomavirus (HPV) is a nonenveloped, circular, double-stranded DNA virus belonging to the Papillomaviridae family. Humans are the only reservoir, and transmission occurs through close skin-to-skin or sexual contact. Human papillomaviruses infect basal epithelial cells and can affect cell-regulatory proteins to result in cell proliferation. Papillomavirus (HPV) infection
    • Atrophic gastritis Gastritis Gastritis refers to inflammation of the gastric mucosa. Gastritis may occur suddenly (acute gastritis) or slowly over time (chronic gastritis). Gastritis may be asymptomatic or with symptoms, including burning abdominal pain (which either worsens or improves with eating), dyspepsia, nausea, and vomiting. Gastritis
    • Tylosis (Howel-Evans syndrome): autosomal dominant Autosomal dominant Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal dominant diseases are expressed when only 1 copy of the dominant allele is inherited. Autosomal Recessive and Autosomal Dominant Inheritance disease with hyperkeratosis Hyperkeratosis Ichthyosis Vulgaris of palm and sole 
    • Plummer-Vinson syndrome Plummer-Vinson syndrome A syndrome of dysphagia with iron-deficiency anemia that is due to congenital anomalies in the esophagus (such as cervical esophageal webs). It is known as patterson-kelly syndrome in the united kingdom. Iron Deficiency Anemia
    • Poor oral hygiene
    • Nitrosamine exposure Exposure ABCDE Assessment (e.g., cured meats)
    • Drinking scalding-hot liquids
    • Areca nut or betel quid chewing
Table: Epidemiology of and risk factors for esophageal cancer
Adenocarcinoma Squamous cell carcinoma Squamous cell carcinoma Cutaneous squamous cell carcinoma (cSCC) is caused by malignant proliferation of atypical keratinocytes. This condition is the 2nd most common skin malignancy and usually affects sun-exposed areas of fair-skinned patients. The cancer presents as a firm, erythematous, keratotic plaque or papule. Squamous Cell Carcinoma (SCC)
Sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria Male Male
Race Caucasians African Americans, Asians
Major risk factors Barrett’s esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy, smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases, obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases, alcohol consumption, low vegetable and fruit intake, drinking hot liquids, caustic strictures, achalasia Achalasia Achalasia is a primary esophageal motility disorder that develops from the degeneration of the myenteric plexus. This condition results in impaired lower esophageal sphincter relaxation and absence of normal esophageal peristalsis. Patients typically present with dysphagia to solids and liquids along with regurgitation. Achalasia

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6:16
Esophageal Cancer

Clinical Presentation and Complications

Clinical presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor

  • Asymptomatic in early stages 
  • Signs and symptoms:
    • Progressive dysphagia Dysphagia Dysphagia is the subjective sensation of difficulty swallowing. Symptoms can range from a complete inability to swallow, to the sensation of solids or liquids becoming “stuck.” Dysphagia is classified as either oropharyngeal or esophageal, with esophageal dysphagia having 2 sub-types: functional and mechanical. Dysphagia (from solids to liquids):
      • Due to obstruction by the tumor Tumor Inflammation
      • Noted when esophageal lumen is < 13 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma
    • Weight loss Weight loss Decrease in existing body weight. Bariatric Surgery (from dysphagia Dysphagia Dysphagia is the subjective sensation of difficulty swallowing. Symptoms can range from a complete inability to swallow, to the sensation of solids or liquids becoming “stuck.” Dysphagia is classified as either oropharyngeal or esophageal, with esophageal dysphagia having 2 sub-types: functional and mechanical. Dysphagia and tumor Tumor Inflammation-related anorexia Anorexia The lack or loss of appetite accompanied by an aversion to food and the inability to eat. It is the defining characteristic of the disorder anorexia nervosa. Anorexia Nervosa)
    • Odynophagia Odynophagia Epiglottitis in 20% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship
Table: Esophageal cancers—differences in presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor
Adenocarcinoma Squamous cell carcinoma Squamous cell carcinoma Cutaneous squamous cell carcinoma (cSCC) is caused by malignant proliferation of atypical keratinocytes. This condition is the 2nd most common skin malignancy and usually affects sun-exposed areas of fair-skinned patients. The cancer presents as a firm, erythematous, keratotic plaque or papule. Squamous Cell Carcinoma (SCC)
Location (major distinguishing factor) Distal â…“ of esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy Esophagogastric junction Esophagogastric junction The area covering the terminal portion of esophagus and the beginning of stomach at the cardiac orifice. Esophagus: Anatomy (EGJ) Proximal two-thirds of esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy
Early lesions
  • Mucosal irregularities, ulcer, or nodule Nodule Chalazion
  • Detected due to surveillance Surveillance Developmental Milestones and Normal Growth of Barrett’s esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy
Advanced lesions Ulcerated or exophytic Exophytic Retinoblastoma mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast with obstruction Infiltrating or ulcerated mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast, may be circumferential

Complications

  • Iron Iron A metallic element with atomic symbol fe, atomic number 26, and atomic weight 55. 85. It is an essential constituent of hemoglobins; cytochromes; and iron-binding proteins. It plays a role in cellular redox reactions and in the transport of oxygen. Trace Elements-deficiency anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types secondary to chronic gastrointestinal bleeding Gastrointestinal bleeding Gastrointestinal bleeding (GIB) is a symptom of multiple diseases within the gastrointestinal (GI) tract. Gastrointestinal bleeding is designated as upper or lower based on the etiology’s location to the ligament of Treitz. Depending on the location of the bleeding, the patient may present with hematemesis (vomiting blood), melena (black, tarry stool), or hematochezia (fresh blood in stools). Gastrointestinal Bleeding
  • Local tumor Tumor Inflammation spread:
    • Cough ( trachea Trachea The trachea is a tubular structure that forms part of the lower respiratory tract. The trachea is continuous superiorly with the larynx and inferiorly becomes the bronchial tree within the lungs. The trachea consists of a support frame of semicircular, or C-shaped, rings made out of hyaline cartilage and reinforced by collagenous connective tissue. Trachea: Anatomy)
    • Hoarseness Hoarseness An unnaturally deep or rough quality of voice. Parapharyngeal Abscess and vocal paralysis (recurrent laryngeal nerve)
    • Tracheoesophageal fistulas (direct invasion through the esophageal wall and main stem bronchus)
  • Metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis:
    • Compressive symptoms from lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs node metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis (aortic, liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy, lung, mediastinal)
    • SCC: usually intrathoracic
    • AC: usually intraabdominal

Diagnosis

Diagnosis

  • Initial work-up of dysphagia Dysphagia Dysphagia is the subjective sensation of difficulty swallowing. Symptoms can range from a complete inability to swallow, to the sensation of solids or liquids becoming “stuck.” Dysphagia is classified as either oropharyngeal or esophageal, with esophageal dysphagia having 2 sub-types: functional and mechanical. Dysphagia: 
  • Upper endoscopy Endoscopy Procedures of applying endoscopes for disease diagnosis and treatment. Endoscopy involves passing an optical instrument through a small incision in the skin i.e., percutaneous; or through a natural orifice and along natural body pathways such as the digestive tract; and/or through an incision in the wall of a tubular structure or organ, i.e. Transluminal, to examine or perform surgery on the interior parts of the body. Gastroesophageal Reflux Disease (GERD): 
  • Endoscopic biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma with brush cytology or image-guided biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma (for metastatic site):
    • Adenocarcinoma: 
    • SCC: 
      • Keratin Keratin A class of fibrous proteins or scleroproteins that represents the principal constituent of epidermis; hair; nails; horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms a coiled-coil alpha helical structure consisting of type I keratin and a type II keratin, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. Alpha-keratins have been classified into at least 20 subtypes. In addition multiple isoforms of subtypes have been found which may be due to gene duplication. Seborrheic Keratosis pearls: clusters of neoplastic cells with circular keratinization
      • Individual cell keratinization and intercellular bridges

Evaluation for regional disease and metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis

  • Endoscopic ultrasound (EUS):
  • Bronchoscopy Bronchoscopy Endoscopic examination, therapy or surgery of the bronchi. Laryngomalacia and Tracheomalacia:
  • Laryngoscopy:
    • Indicated for cervical SCC
    • Determines presence of concomitant SCC of the head and neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess
  • Chest and abdominal computed tomography (CT) and/or positron emission tomography ( PET PET An imaging technique that combines a positron-emission tomography (PET) scanner and a ct X ray scanner. This establishes a precise anatomic localization in the same session. Nuclear Imaging)
    • For detection of metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis
    • Integrated fluorodeoxyglucose (FDG)- PET PET An imaging technique that combines a positron-emission tomography (PET) scanner and a ct X ray scanner. This establishes a precise anatomic localization in the same session. Nuclear Imaging/CT available for occult metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis
  • Upper esophageal carcinoma

    Barium esophagogram: Left image shows an upper esophageal carcinoma (arrow). Right image shows the carcinoma downstaged effectively after neoadjuvant chemotherapy Neoadjuvant Chemotherapy Osteosarcoma.

    Image: “Upper esophageal carcinoma” by Department of Thoracic Surgery Thoracic Surgery Basic surgical intervention in the thoracic cavity has the primary goal of alleviating any malady that mechanically affects the function of the heart and lungs, which can be secondary to underlying pathologies or, most commonly, trauma. Interventions include tube thoracostomy, thoracentesis, and emergency thoracotomy. Thoracic Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China. License: CC BY 4.0
  • Late-stage squamous cell carcinoma of the esophagus

    Esophagogastroduodenoscopy (EGD) showing cancer outgrowth ( squamous cell carcinoma Squamous cell carcinoma Cutaneous squamous cell carcinoma (cSCC) is caused by malignant proliferation of atypical keratinocytes. This condition is the 2nd most common skin malignancy and usually affects sun-exposed areas of fair-skinned patients. The cancer presents as a firm, erythematous, keratotic plaque or papule. Squamous Cell Carcinoma (SCC)), causing a narrowing of the lumen

    Image: “A Late-Stage Squamous Cell Carcinoma Squamous cell carcinoma Cutaneous squamous cell carcinoma (cSCC) is caused by malignant proliferation of atypical keratinocytes. This condition is the 2nd most common skin malignancy and usually affects sun-exposed areas of fair-skinned patients. The cancer presents as a firm, erythematous, keratotic plaque or papule. Squamous Cell Carcinoma (SCC)” by Brooks PJ, Enoch M-A, Goldman D, Li T-K, Yokoyama A. License: C BY 2.5
  • Successfully treated advanced esophageal cancer

    PET PET An imaging technique that combines a positron-emission tomography (PET) scanner and a ct X ray scanner. This establishes a precise anatomic localization in the same session. Nuclear Imaging–CT findings of esophageal cancer.
    a. PET PET An imaging technique that combines a positron-emission tomography (PET) scanner and a ct X ray scanner. This establishes a precise anatomic localization in the same session. Nuclear Imaging–CT scan showing accumulation in the middle esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy, representing the squamous cell carcinoma Squamous cell carcinoma Cutaneous squamous cell carcinoma (cSCC) is caused by malignant proliferation of atypical keratinocytes. This condition is the 2nd most common skin malignancy and usually affects sun-exposed areas of fair-skinned patients. The cancer presents as a firm, erythematous, keratotic plaque or papule. Squamous Cell Carcinoma (SCC) (arrows).
    b. PET PET An imaging technique that combines a positron-emission tomography (PET) scanner and a ct X ray scanner. This establishes a precise anatomic localization in the same session. Nuclear Imaging–CT scan after 4 courses of chemotherapy Chemotherapy Osteosarcoma showing the disappearance of accumulation in the primary tumor Tumor Inflammation (arrows).
    c. PET PET An imaging technique that combines a positron-emission tomography (PET) scanner and a ct X ray scanner. This establishes a precise anatomic localization in the same session. Nuclear Imaging–CT scan showing accumulation in the left axillary lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs node (arrow).
    d. PET PET An imaging technique that combines a positron-emission tomography (PET) scanner and a ct X ray scanner. This establishes a precise anatomic localization in the same session. Nuclear Imaging–CT scan after 4 courses of treatment showing the disappearance of accumulation in the left axillary lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs node (arrow).

    Image: “ PET PET An imaging technique that combines a positron-emission tomography (PET) scanner and a ct X ray scanner. This establishes a precise anatomic localization in the same session. Nuclear Imaging–CT” by Department of Surgery, Iwate Medical University School of Medicine, Iwate, Japan. License: CC BY 4.0

Staging Staging Methods which attempt to express in replicable terms the extent of the neoplasm in the patient. Grading, Staging, and Metastasis

Tumor Tumor Inflammation, node, metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis (TNM) staging Staging Methods which attempt to express in replicable terms the extent of the neoplasm in the patient. Grading, Staging, and Metastasis:

  • T: extent of tumor Tumor Inflammation in the esophageal wall 
    • T1: mucosa (innermost layer) and submucosa
    • T2: muscularis propria
    • T3 T3 A T3 thyroid hormone normally synthesized and secreted by the thyroid gland in much smaller quantities than thyroxine (T4). Most T3 is derived from peripheral monodeiodination of T4 at the 5′ position of the outer ring of the iodothyronine nucleus. The hormone finally delivered and used by the tissues is mainly t3. Thyroid Hormones: adventitia (outermost layer)
    • T4 T4 The major hormone derived from the thyroid gland. Thyroxine is synthesized via the iodination of tyrosines (monoiodotyrosine) and the coupling of iodotyrosines (diiodotyrosine) in the thyroglobulin. Thyroxine is released from thyroglobulin by proteolysis and secreted into the blood. Thyroxine is peripherally deiodinated to form triiodothyronine which exerts a broad spectrum of stimulatory effects on cell metabolism. Thyroid Hormones: involves adjacent structures of the esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy
  • N: regional lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs nodes involved
  • M: presence of distant metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis
Esophageal cancer staging

Locoregional esophageal cancer staging Staging Methods which attempt to express in replicable terms the extent of the neoplasm in the patient. Grading, Staging, and Metastasis: The cancer is seen as the lesion penetrating the esophageal wall. Illustration depicts the staging Staging Methods which attempt to express in replicable terms the extent of the neoplasm in the patient. Grading, Staging, and Metastasis from T1 (mucosa and submucosa) to advanced disease, involving adjacent structures in T4 T4 The major hormone derived from the thyroid gland. Thyroxine is synthesized via the iodination of tyrosines (monoiodotyrosine) and the coupling of iodotyrosines (diiodotyrosine) in the thyroglobulin. Thyroxine is released from thyroglobulin by proteolysis and secreted into the blood. Thyroxine is peripherally deiodinated to form triiodothyronine which exerts a broad spectrum of stimulatory effects on cell metabolism. Thyroid Hormones and the lymph nodes Lymph Nodes They are oval or bean shaped bodies (1 – 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy (N).

Image by Lecturio.

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2:38
Esophageal Cancer with Case

Management and Prognosis

Curative treatment options

  • Endoscopic mucosal resection: 
    • For early cancer (limited to mucosa) or high-grade dysplasia Dysplasia Cellular Adaptation (HGD) in Barrett’s esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy
    • Lesion with diameter ≤ 2 cm
    • < â…“ of the circumference of the esophageal wall involved
  • Surgery:
    • Esophagectomy:
      • Lesion penetrating up to the submucosa (T1 with no regional lymph nodes Lymph Nodes They are oval or bean shaped bodies (1 – 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy, no metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis)
      • In some centers, lesions penetrating up to muscularis propria (T2) can be resected.
    • Esophagectomy following neoadjuvant chemotherapy Neoadjuvant Chemotherapy Osteosarcoma or followed by chemoradiotherapy:
      • For locally advanced tumors ( T3 T3 A T3 thyroid hormone normally synthesized and secreted by the thyroid gland in much smaller quantities than thyroxine (T4). Most T3 is derived from peripheral monodeiodination of T4 at the 5′ position of the outer ring of the iodothyronine nucleus. The hormone finally delivered and used by the tissues is mainly t3. Thyroid Hormones) with or without nodal disease
      • Selected patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with T4 T4 The major hormone derived from the thyroid gland. Thyroxine is synthesized via the iodination of tyrosines (monoiodotyrosine) and the coupling of iodotyrosines (diiodotyrosine) in the thyroglobulin. Thyroxine is released from thyroglobulin by proteolysis and secreted into the blood. Thyroxine is peripherally deiodinated to form triiodothyronine which exerts a broad spectrum of stimulatory effects on cell metabolism. Thyroid Hormones disease
    • Contraindication to surgery: 
  • Chemoradiation:
    • Use of radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma therapy and chemotherapy Chemotherapy Osteosarcoma 
    • For downstaging the tumor Tumor Inflammation for later resection or as definitive treatment
    • 2–3 drug cytotoxic Cytotoxic Parvovirus B19 regimen used due to higher response rate

Palliative options

  • For advanced esophageal cancer (metastatic disease)
  • Goals:
    • Symptom palliation and comfort
    • Prolong survival 
  • Chemoradiation 
  • Assess for positive HER2 HER2 A cell surface protein-tyrosine kinase receptor that is overexpressed in a variety of adenocarcinomas. It has extensive homology to and heterodimerizes with the EGF receptor, the ERBB-3 receptor, and the ERBB-4 receptor. Activation of the erbB-2 receptor occurs through heterodimer formation with a ligand-bound erbB receptor family member. Targeted and Other Nontraditional Antineoplastic Therapy (human epidermal growth factor 2) status of adenocarcinoma: add trastuzumab Trastuzumab A humanized monoclonal antibody against the ErbB-2 receptor (HER2). As an antineoplastic agent, it is used to treat breast cancer where HER2 is overexpressed. Targeted and Other Nontraditional Antineoplastic Therapy, a monoclonal antibody targeting the HER2 HER2 A cell surface protein-tyrosine kinase receptor that is overexpressed in a variety of adenocarcinomas. It has extensive homology to and heterodimerizes with the EGF receptor, the ERBB-3 receptor, and the ERBB-4 receptor. Activation of the erbB-2 receptor occurs through heterodimer formation with a ligand-bound erbB receptor family member. Targeted and Other Nontraditional Antineoplastic Therapy receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors
  • Endoscopic procedures:
    • Dilation
    • Stenting
    • Laser ablation

Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas

  • Depends on the stage of disease
  • 50%–80% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship on presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor have locally advanced or metastatic esophageal cancer.
  • Low survival rate noted in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs node or distant metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis 
  • Overexpression of HER2 HER2 A cell surface protein-tyrosine kinase receptor that is overexpressed in a variety of adenocarcinomas. It has extensive homology to and heterodimerizes with the EGF receptor, the ERBB-3 receptor, and the ERBB-4 receptor. Activation of the erbB-2 receptor occurs through heterodimer formation with a ligand-bound erbB receptor family member. Targeted and Other Nontraditional Antineoplastic Therapy receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors: associated with aggressive cancer growth and poor survival

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Cardiothoracic Surgery: Esophageal Cancer

Differential Diagnosis

  • Barrett’s esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy: results from chronic gastroesophageal reflux disease Gastroesophageal Reflux Disease Gastroesophageal reflux disease (GERD) occurs when the stomach acid frequently flows back into the esophagus. This backwash (acid reflux) can irritate the lining of the esophagus, causing symptoms such as retrosternal burning pain (heartburn). Gastroesophageal Reflux Disease (GERD) ( GERD GERD Gastroesophageal reflux disease (GERD) occurs when the stomach acid frequently flows back into the esophagus. This backwash (acid reflux) can irritate the lining of the esophagus, causing symptoms such as retrosternal burning pain (heartburn). Gastroesophageal Reflux Disease (GERD)) leading to replacement of esophageal squamous epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium: Histology by gastric columnar epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium: Histology. Barrett’s esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy is a risk factor for esophageal adenocarcinoma. Surveillance Surveillance Developmental Milestones and Normal Growth is recommended to detect dysplasia Dysplasia Cellular Adaptation or adenocarcinoma early enough to provide treatment.
  • Esophageal stricture Stricture Primary Sclerosing Cholangitis: narrowing of the esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy that can result from GERD GERD Gastroesophageal reflux disease (GERD) occurs when the stomach acid frequently flows back into the esophagus. This backwash (acid reflux) can irritate the lining of the esophagus, causing symptoms such as retrosternal burning pain (heartburn). Gastroesophageal Reflux Disease (GERD), malignancies, and caustic ingestion Caustic Ingestion Caustic agents are acidic or alkaline substances that damage tissues severely if ingested. Alkali ingestion typically damages the esophagus via liquefactive necrosis, whereas acids cause more severe gastric injury leading to coagulative necrosis. Caustic Ingestion (Cleaning Products). The condition presents with dysphagia Dysphagia Dysphagia is the subjective sensation of difficulty swallowing. Symptoms can range from a complete inability to swallow, to the sensation of solids or liquids becoming “stuck.” Dysphagia is classified as either oropharyngeal or esophageal, with esophageal dysphagia having 2 sub-types: functional and mechanical. Dysphagia to solids, progressing to liquids. Barium swallow Barium Swallow Imaging of the Intestines study shows a narrowed luminal diameter. Upper endoscopy Endoscopy Procedures of applying endoscopes for disease diagnosis and treatment. Endoscopy involves passing an optical instrument through a small incision in the skin i.e., percutaneous; or through a natural orifice and along natural body pathways such as the digestive tract; and/or through an incision in the wall of a tubular structure or organ, i.e. Transluminal, to examine or perform surgery on the interior parts of the body. Gastroesophageal Reflux Disease (GERD) allows for biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma and dilation when necessary.
  • Esophageal spasm: presents with dysphagia Dysphagia Dysphagia is the subjective sensation of difficulty swallowing. Symptoms can range from a complete inability to swallow, to the sensation of solids or liquids becoming “stuck.” Dysphagia is classified as either oropharyngeal or esophageal, with esophageal dysphagia having 2 sub-types: functional and mechanical. Dysphagia to solids and liquids but is associated with sudden onset of chest pain Chest Pain Chest pain is one of the most common and challenging complaints that may present in an inpatient and outpatient setting. The differential diagnosis of chest pain is large and includes cardiac, gastrointestinal, pulmonary, musculoskeletal, and psychiatric etiologies. Chest Pain that is not exertion-related. There are 2 types of esophageal spasm: distal esophageal spasm and hypercontractile esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy. Manometry Manometry Measurement of the pressure or tension of liquids or gases with a manometer. Achalasia shows characteristic esophageal contractions with normal relaxation of the esophagogastric junction Esophagogastric junction The area covering the terminal portion of esophagus and the beginning of stomach at the cardiac orifice. Esophagus: Anatomy. 
  • Achalasia Achalasia Achalasia is a primary esophageal motility disorder that develops from the degeneration of the myenteric plexus. This condition results in impaired lower esophageal sphincter relaxation and absence of normal esophageal peristalsis. Patients typically present with dysphagia to solids and liquids along with regurgitation. Achalasia: an esophageal motility Esophageal Motility Gastrointestinal Motility disorder that develops from degeneration of the myenteric plexus Myenteric plexus One of two ganglionated neural networks which together form the enteric nervous system. The myenteric (Auerbach’s) plexus is located between the longitudinal and circular muscle layers of the gut. Its neurons project to the circular muscle, to other myenteric ganglia, to submucosal ganglia, or directly to the epithelium, and play an important role in regulating and patterning gut motility. Gastrointestinal Neural and Hormonal Signaling. There is impaired lower esophageal sphincter Lower Esophageal Sphincter Esophagus: Anatomy relaxation and absence of normal esophageal peristalsis Peristalsis A movement, caused by sequential muscle contraction, that pushes the contents of the intestines or other tubular organs in one direction. Gastrointestinal Motility. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship present with dysphagia Dysphagia Dysphagia is the subjective sensation of difficulty swallowing. Symptoms can range from a complete inability to swallow, to the sensation of solids or liquids becoming “stuck.” Dysphagia is classified as either oropharyngeal or esophageal, with esophageal dysphagia having 2 sub-types: functional and mechanical. Dysphagia to solids and liquids along with regurgitation Regurgitation Gastroesophageal Reflux Disease (GERD). Diagnosis is established by high-resolution manometry Manometry Measurement of the pressure or tension of liquids or gases with a manometer. Achalasia. 
  • Esophageal ring and web: thin structures that produce partial occlusion of the esophageal lumen. Plummer-Vinson syndrome Plummer-Vinson syndrome A syndrome of dysphagia with iron-deficiency anemia that is due to congenital anomalies in the esophagus (such as cervical esophageal webs). It is known as patterson-kelly syndrome in the united kingdom. Iron Deficiency Anemia consists of iron Iron A metallic element with atomic symbol fe, atomic number 26, and atomic weight 55. 85. It is an essential constituent of hemoglobins; cytochromes; and iron-binding proteins. It plays a role in cellular redox reactions and in the transport of oxygen. Trace Elements-deficiency anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types, dysphagia Dysphagia Dysphagia is the subjective sensation of difficulty swallowing. Symptoms can range from a complete inability to swallow, to the sensation of solids or liquids becoming “stuck.” Dysphagia is classified as either oropharyngeal or esophageal, with esophageal dysphagia having 2 sub-types: functional and mechanical. Dysphagia, and a cervical esophageal web. Schatzki’s ring is the most common type of esophageal ring. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship present with dysphagia Dysphagia Dysphagia is the subjective sensation of difficulty swallowing. Symptoms can range from a complete inability to swallow, to the sensation of solids or liquids becoming “stuck.” Dysphagia is classified as either oropharyngeal or esophageal, with esophageal dysphagia having 2 sub-types: functional and mechanical. Dysphagia to solids. Diagnosis is by barium swallow Barium Swallow Imaging of the Intestines study and upper endoscopy Endoscopy Procedures of applying endoscopes for disease diagnosis and treatment. Endoscopy involves passing an optical instrument through a small incision in the skin i.e., percutaneous; or through a natural orifice and along natural body pathways such as the digestive tract; and/or through an incision in the wall of a tubular structure or organ, i.e. Transluminal, to examine or perform surgery on the interior parts of the body. Gastroesophageal Reflux Disease (GERD).

References

  1. Abbas, G., Krasna, M. (2017). Overview of esophageal cancer. Ann Cardiothorac Surg 6(2):131–136. https://pubmed.ncbi.nlm.nih.gov/28447001/ 
  2. Gibson, M., Tanabe, K., Goldberg, R., Savarese, D. (2020). Epidemiology and pathobiology of esophageal cancer. UpToDate. Retrieved 14 Oct 2020, from https://www.uptodate.com/contents/epidemiology-and-pathobiology-of-esophageal-cancer
  3. Jain, S., Dhingra, S. (2017). Pathology of esophageal cancer and Barrett’s esophagus. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5387146/
  4. Kumar, V., Abbas, A.K., Aster, J. (2020). The gastrointestinal tract in Robbins and Cotran Pathologic Basis of Disease (10th ed., pp. 762–764), Elsevier, Inc.
  5. Masab, M., Espat, J. (2020) Esophageal cancer. Medscape. Retrieved 14 Oct 2020, from https://emedicine.medscape.com/article/277930-overview
  6. Recio-Boiles, A., Babiker, H. (2020). Esophageal cancer. https://www.ncbi.nlm.nih.gov/books/NBK459267/
  7. Saltzman, J., Howell, D., Goldberg, R., Savarese, D. (2018). Clinical manifestations, diagnosis, and staging of esophageal cancer. UpToDate. Retrieved 14 Oct 2020, from https://www.uptodate.com/contents/clinical-manifestations-diagnosis-and-staging-of-esophageal-cancer
  8. Smyth, E., Lagergren, J., Fitzgerald, R., Lordick, F., Shah, M., Lagergren, P, Cunningham, D. (2017). Oesophageal Cancer. doi: 10.1038/nrdp.2017.48
  9. Swofford, B., Dragovich, T. (2017). Durable and Complete Response to Herceptin Monotherapy in Patients with Metastatic Esophageal Cancer. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5803686/
  10. Wright, C., Saltzman, J., Tanabe, K., Savarese, D. (2020). Management of superficial esophageal cancer. Retrieved 14 Oct 2020, from https://www.uptodate.com/contents/management-of-superficial-esophageal-cancer
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