Introduction
- Aggressive course due to lack of serosa in oesophageal wall
- Barret’s oesophagus is the only known precursor to adenocarcinoma
Epidemiology
- 8th M/C cancer worldwide
- 6th M/C cause of cancer-related deaths worldwide
Oesophageal cancer belt:
Stretches from northern China (where annual incidence rates are up to 100/100,000 population) through the central Asian republics to Northern Iran
Aetiology
Oesophageal squamous cell carcinoma (OSCC) (M/C, 70% worldwide)
A history of smoking, alcohol consumption, and a diet low in fruits and vegetables accounts for almost 90% of OSCC, usually in the upper 2⁄3 of oesophagus
- Poor nutritional status
- Low intake of fruit and vegetables
- Drinking beverages at high temperatures
- Human papillomavirus (HPV) infection
- Preexisting anatomical diseases: Achalasia, caustic strictures, gastrectomy, and atrophic gastritis
- Syndromic associations:
- Tylosis (40-90% risk by age 70): Rare autosomal dominant syndrome associated with non-epidermolytic palmoplantar keratosis (or Howel-Evans syndrome) due to TEC (tylosis with esophageal cancer) gene
- Bloom syndrome: Rare autosomal recessive syndrome associated with leukemia, lymphomas, and Wilms tumor (or chromosomal breakage syndrome) due to BLM gene mutation
- Fanconi anemia: Autosomal recessive disorder with congenital malformations, pancytopenia, and risk for hematologic malignancies
- Oral bisphosphonates have been linked to esophageal squamous cell carcinoma and adenocarcinoma.
Oesophageal adenocarcinoma (OAC) (M/C in USA)
Usually lower 1⁄3 of oesophagus
- Barrett’s oesophagus metaplasia (80% cases):
- Risk factors: History of smoking, high BMI, GERD, and low fruit and vegetable diet
- Alcohol intake not associated with adenocarcinoma
- Protective factors: High cereal diet, antioxidants, fruits and vegetables, folate, vitamin C, proton-pump inhibitors, and NSAIDs
- Associated with epidermal growth factor polymorphisms, Helicobacter pylori infection, and other conditions which increase esophageal acid exposure including (e.g., Zollinger-Ellison syndrome, scleroderma, lower esophageal sphincter relaxing drugs, or procedures)
- Risk factors: History of smoking, high BMI, GERD, and low fruit and vegetable diet
Pathophysiology
Oesophageal squamous cell carcinoma (OSCC): Arises from small polypoid excrescences, denuded epithelium, and plaques, commonly located at the mid-portion of the esophagus.
Early lesions: Subtle, and tissue staining with Lugol’s iodine should be used to stain normal squamous epithelium containing glycogen from malignant squamous glycogen-deprived cells to facilitate diagnosis.
Advance lesions are ulcerated, circumferential, infiltrate submucosa, and extend in a cephalad direction.
Spread occurs via the lymphatic system to regional lymph nodes, but a third of patients will have distant metastases to liver, lung, and bone including invasion of malignant cells to the bone marrow.
OAC: Approximately 60% of adenocarcinoma of the distal esophagus and more typically, GEJ cases, arise from Barrett’s esophagus metaplastic epithelium. The typical treatment for patients with Barrett’s esophagus is surveillance using upper endoscopy and biopsy to examine tissue for evidence of dysplasia. The incidence rate for adenocarcinoma among patients without dysplasia is 1.0 case per 1000 person-years; on the other hand, detection of low-grade dysplasia on the index endoscopy is associated with an adenocarcinoma incidence rate of 5.1 cases per 1000 person-years. The annual risk of esophageal adenocarcinoma is 0.12% (95% CI; 0.09, 0.15). High-grade dysplasia should be managed aggressively, including the possibility for surgical resection. Early metastases occur in adjacent or regional lymph nodes. Predictors such as tumor markers, (TP53), may indicate potential progression to malignant disease.
Clinical features
Common features:
- Progressive solid food dysphagia (M/C presentation in both types): Due to locally advanced cancer causing obstruction and dysphagia to liquid manifests in advanced stages.
- Cachexia and substantial weight loss: Consequences of dysphagia, and may also represent advanced disease
Other features:
- Non-specific symptoms: Retrosternal discomfort or burning sensation.
- Other features: Hematemesis, melena, anemia symptoms, regurgitation and aspiration pneumonia (rare)
- Tracheobronchial wall invasion causing fistulas can present clinically with laryngeal nerve paralysis, cough, and/or post-obstructive pneumonia.
Diagnosis
Chest radiograph:
Computed tomography (CT): Thorax & abdomen
Best initial modality for detection of the distant metastasis, gross direct invasion, and enlarged lymph nodes.
Endoscopic ultrasound (EUS):
Standard of therapy technique for locoregional staging, with up to 90% accuracy in assessing tumor depth and locoregional and mediastinal lymph nodes involvement. It is the most sensitive modality for assessment of the depth of invasion and regional enlarged lymph nodes.
Positron emission tomography CT (PET/CT):
PET can be useful for re-staging after the initial neoadjuvant therapy.
Endoscopy:
TNM staging:
A combination of CT scan, transesophageal ultrasound, and PET/CT scan are used for staging of the disease.
Management
Endoscopic resection:
For superficial, limited mucosa disease (< T1a)
- Alternative techniques: Endoscopic mucosal resection or endoscopic submucosal dissection or endoscopic ablation (cryoablation, radiofrequency ablation, and photodynamic therapy)
Surgical management:
Direct surgical resection with lymphadenectomy for lesions penetrating the submucosa with negative lymph nodes (> T1b)
Chemotherapy:
Neoadjuvant chemoradiation of resectable lesions invading muscularis propria with positive lymph nodes (< T2N1)
- Palliative systemic therapy for those locally advanced unresectable or metastatic disease
Summary
