• Clinical science

Esophageal cancer

Abstract

Esophageal cancer typically assumes the form of adenocarcinoma or squamous cell carcinoma, although there are some rarer tumors. Adenocarcinomas are considered the fastest growing neoplasia in Western countries, while squamous cell carcinoma is still most common in the developing world. Adenocarcinoma, which usually affects the lower third of the esophagus, may be preceded by Barrett's esophagus, a complication of gastroesophageal reflux disease (GERD). In addition to GERD, other risk factors include obesity and smoking. Squamous cell carcinomas mostly occur in the upper two-thirds of the esophagus. Known risk factors for squamous cell carcinoma include carcinogen exposure from alcohol and tobacco consumption, and dietary factors (e.g., diet low in fruits and vegetables). Esophageal cancers are often asymptomatic in early stages of the disease. Locally advanced disease is common at presentation, progressive dysphagia being the primary symptom. Hoarseness, weight loss, and hematemesis may also be present. Endoscopy is the primary diagnostic test, enabling direct visualization and biopsy of the lesion for histopathological confirmation. Curative surgical resection may be considered for locally invasive cancers. Esophageal cancer is unresectable at presentation in about 60% of patients. Chemotherapy, radiation, and palliative stenting play a role in the management of unresectable disease.

Epidemiology

  • Sex: > (3:1)
  • Peak incidence: 60–70 years of age
  • Adenocarcinoma: most common type of esophageal cancer in the United States
  • Squamous cell carcinoma (SCC): most common type worldwide

References:[1][2][3]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

Adenocarcinoma

Squamous cell carcinoma (SCC)

  • Risk factors
    • Alcohol consumption
    • Smoking
    • Diet low in fruits and vegetables
    • Drinking hot beverages
    • Diverticula (e.g., Zenker's diverticulum)
    • Achalasia
    • Nitrosamines exposure (e.g., cured meat, fish, bacon)
    • Radiotherapy
    • Esophageal web
    • Plummer-Vinson syndrome
    • Esophageal candidiasis
  • Localization: mostly in the upper ⅔ of the esophagus

The primary risk factors for squamous cell esophageal cancer are alcohol consumption, smoking, and dietary factors (e.g., diet low in fruits and vegetables)!

References:[4][5]

Clinical features

  • Early stages: Often asymptomatic but may present with swallowing difficulties or retrosternal discomfort, especially if the following occurs:
    • Early lymphogenous metastasis
    • Early infiltration of adjacent structures
  • Late stages
    • Common
      • Progressive dysphagia (from solids to liquids) with possible odynophagia
      • Weight loss
      • Retrosternal chest or back pain
      • Anemia
    • Less common

Esophageal cancer is a "silent" disease and typically becomes symptomatic at advanced stages!

References:[1][5][6][7]

Stages

TNM Classification of Malignant Tumors

TNM Description
T1 Infiltration of the lamina propria (T1a) and submucous layer (T1b)
T2 Infiltration of the muscularis propria
T3 Infiltration of the adventitia
T4

Infiltration of adjacent structures (T4a: pleura, pericardium, diaphragm; T4b: other structures, e.g., aorta, vertebral body, trachea)

N1 1–2 regional lymph nodes involved
N2 3–6 regional lymph nodes involved
N3 ≥ 7 regional lymph nodes involved
M1 Hematogenous metastasis or non-regional lymph nodes involved

UICC (Union for International Cancer Control) Staging System

Stage TNM
I IA T1, N0, M0
IB T2, N0, M0
II IIA T3, N0, M0
IIB up to T2, N1, M0
III

T4, N0, M0

from T3, N1, M0

from N2, M0

IV M1

Diagnostics

  • Esophagogastroduodenoscopy (best initial and confirmatory test)
    • Direct visualization of the tumor
    • Biopsy of any suspicious lesions
  • Barium swallow: asymmetrical and irregular borders of the esophagus with characteristic stenosis and proximal dilatation (apple core lesion)
    • Sensitive, but does not allow confirmation or staging of a malignancy. Inferior to endoscopy, but indicated in the case of:
      • Severe stricture that inhibits endoscopic evaluation
      • Suspected tracheoesophageal fistula due to esophageal cancer
  • Staging

References:[7][1][3][8]

Pathology

Adenocarcinoma

Squamous cell carcinoma

  • Histological characteristics
    • Breakdown of uniform tissue structure
    • Squamous cell carcinoma clusters with circular keratinization
    • Lymphocytic infiltration between the carcinoma clusters

Treatment

Curative

  • Indication
  • Methods
    • Endoscopic submucosal resection for removal of superficial, epithelial lesions
    • Subtotal or total esophagectomy with gastric pull-through procedure or colonic interposition
    • Neoadjuvant chemoradiation
      • For downstaging → potentially allows for later resection
      • As definitive treatment in patients with proven complete response (e.g., during endoscopy)

Palliative

  • Indication: patients with advanced disease (majority of patients)
  • Methods:
    • Chemoradiation
    • Stent placement
    • Other endoscopic treatments (e.g., laser therapy)

References:[2][9][1][10][11][12][8]

Complications

Esophageal cancer metastasizes early because of the absence of serosa in parts of the esophagus!

References:[12][8][5][13]

We list the most important complications. The selection is not exhaustive.

Prognosis

  • Generally poor prognosis because of late diagnosis
  • The more distal the tumor, the better the prognosis.

References:[2][7]