Esophageal Ca

Introduction

  • Overall Mortality high —> ~80%
  • 50% of patients present with unresectable or metastatic disease

Anatomy

  • 25 cm in length
  • Stratified keratinized squamous epithelium
  • From the cricopharyngeus muscle at the level of the cricoid cartilage to the GEJ
  • Lower third (5-10 cm) may contain glandular elements

Barett's Esophagus

  • Replacement of the stratified squamous epithelium with columnar epithelium
  • Z-line
    • The line at which the columnar epithelium transitions to the squamous epithelium (squamocolumnar junction)
    • Normally: Z-line= GEJ
    • In Barrett’s esophagus: the columnar epithelium extends proximally up the esophagus
  • Four esophageal wall layers:
    • Epithelial layer
    • Inner circular muscle layer
    • Outer longitudinal muscle layer
    • Adventitia
    • No serosa
      • ==> facilitating extra esophageal spread of disease.
  • Carina —> 25 cm from the incisors
  • GEJ —> 40 cm from the incisors

Anatomic regions:

  • Cervical
    • Begins: Cricopharyngeus muscle (C7; 15 cm from the incisors)
    • To: Thoracic inlet (T3; 18 cm from the incisors, at the level of the suprasternal notch).
  • Thoracic
    • From: T3-T10 or T11
    • To: GEJ
      • Endoscopically:where the first gastric fold is encountered
      • Histologically: Squamocolumnar junction
    • Thoracic Esophagus is divided to:
      • Upper
      • Mid
      • Lower
  • GEJ Tumours:
    • >1 cm above GEJ
      • Type I AdenoCa
    • Within 1 cm cephalad to 2 cm caudad to GEJ
      • Type II
    • >2 cm of GEJ
      • Type III

Lymphatic Drainage

  • Extensive, longitudinal interconnecting system of lymphatics
  • In the mucosa and submucosa communicate with the lymphatic channels in the muscle layers throughout
  • Lymph can travel the entire length of the esophagus ==> thus the entire esophagus is at potential risk for lymphatic involvement
  • Up to 8 cm or more of “normal” tissue can exist between gross tumor and micrometastases “skip areas” secondary to this extensive lymphatic network
  • Drain into nodes that usually follow arteries
    • Inferior thyroid artery
    • Bronchial and esophageal arteries
    • Left gastric artery (celiac axis)

Epidemiology and Risk Factors

  • Uncommon
    • 1% of all Ca
    • 6% of all GI Ca
  • Recent dramatic rise in AdenoCa
    • Specially in white males the United States
    • From 1987 —> 30% to 50% now
      • 5-10% increase per year
    • Blacks still diagnosed more frequenlt with SCC
  • 5yr OS —> 10%
  • Median survival —> 9m
  • More common in: China, Iran, and Russia, near the Caspian Sea

Possible Risk Factors in these areas:

  • Arid climate and alkaline soil with these high-risk areas
  • Nitrosamines
  • Inversely to:
    • Riboflavin (B2)
    • Nicotinic acid
    • Magnesium
    • Zinc

Major risk Factors:

  • Smoking
  • Alcohol
  • Diets of corn, wheat, millet, scant amounts of fruits, vegetables, and animal products
  • Plummer-Vinson (Paterson-Kelly) syndrome
    • Iron deficiency anemia & low riboflavin(B2) levels
      • Increased risk for oral cavity, hypopharyngeal, and esophageal cancer
  • Nitrate rich food:
    • Nitrosamines & Nitrosamides
    • Pickled vegetables, alcoholic beverages, cured meats, and fish.
  • Achalasia
  • Caustic burns (especially lye corrosion)
  • Tylosis
    • Hyperkeratosis of the palms and soles
    • Papilloma of the esophagus
    • 38% risk in developing esophageal cancer at a mean age of 45 years
  • Barrett's Esophagus
    • 10-15% risk of developing esophageal adenocarcinoma lifetime
    • Most AdenoCa arise from the metaplastic columnar-lined epithelium
    • Severe & long-standing GERD
      • x44 timesfold risk of adenocarcinoma
  • Obesity
  • Hiatal Hernia

Pattern of spread

  • Upper esophagus tumours invade
    • Recurrent laryngeal nerves
    • Carotid arteries
    • Trachea
  • Middle Esophageal tumours in mediastinum:
    • Tracheoesophageal or bronchoesophageal fistula
  • Lower third of the esophagus
    • Aorta
      • ==> massive hemorrhae
    • Pericardium
      • ==> mediastinitis
    • Empyema

Chance of Nodal mets according to T-stage

Stage Risk of LN(+)
T1 20%
T2 60%
T3 90%
T4 100%

  • Most common sites of metastasis:
    • Lung
    • Liver
    • Bone

History and Ph/E

  • Symptoms usually occurs 3-4m before
  • Dysphagia(90%)
    • Onset; duration
    • Solids vs liquids
  • Odynophagia1 (50%)
  • Weight loss(50%)
    • Extent of weight loss is associated with prognosis
  • Hoarseness
  • Cough
  • Glossopharyngeal neuralgia
  • Hematemesis
  • Hemoptysis
  • Melena
  • Dyspnea
  • Persistent cough <— tracheoesophageal or bronchoesophageal fistula
  • Left recurrent laryngeal nerve or the phrenic nerves involvement ==>
    • Dysphonia or hemidiaphragm paralysis
  • SVCO
  • Horner's syndrome
  • Pleural effusion
  • Exsanguination resulting from aortic communication
  • Abdominal and back pain may occur with celiac axis nodal involvement with lower esophageal tumors.
  • History of alcohol and smoking
  • History of prior H&N Ca
  • Any contraindication for chemo/RT/prior RT

Ph/E

  • General
    • Performance Status
    • Cachetia
    • Anemia
    • Jaundice
  • Look for adenopathy
    • Cervical
    • Supraclavicular
    • Axillary
    • Inguinal
  • Head and Neck exam:
    • Hoarseness
    • Horner syndrom
    • Oral cavity, Oropharynx and Larynx
      • Chance of second Ca high
    • SVCO
    • Liver mass
    • Abdominal mass

Investigations:

  • Flexible Endoscopy
    • Assess
      • Size of the tumour
      • Location of the tumour related to GEJ
      • Brushing and Biopsy
  • Bronchoscopy
    • Invasion of Carina
    • Trachea
  • CT scan Chest and Abdomen
  • Endoscopic US
  • Nodal biopsy
  • If severe obstruction —> Feeding tube
    • Consider J-tube or NG tube
    • No PEG tube (as Stomach will be used as neo-esophagus)
  • CBC
    • Hgb
  • KFT
  • LFT
    • Albumin
  • Electrolytes

Pathology

  • Squamous cell carcinomas
    • Degree of cellular differentiation influences survival
    • Variants:
      • Pseudosarcoma
        • Poorly diff
        • spindle-shaped in the strom resembling fibroblasts
      • Verrucous carcinoma
        • Well differentiated
        • Papillary variant of squamous cell carcinoma
  • SCC in situ
  • Dysplasia
  • Adenocarcinoma
    • Now the predominant histologic type
    • May arise from:
      • Foci of ectopic gastric mucosa
      • Intrinsic esophageal glands
      • Barrett's esophagus
      • Adenoacanthoma
        • If a focus of squamous cell metaplasia is found in an adenocarcinoma
  • Adenoid cystic ca
    • Rare
    • 6th decade
    • Median Survival —> 9m
  • Mucoepidermoid tumors (adenosquamous carcinomas)
    • Aggressive
    • Poor prognosis
  • Small-cell carcinoma
    • 2%
    • Sixth to eighth decades of life
    • Middle to lower esophagus in males
    • Argyrophilic cells in the esophagus
    • Paraneoplastic syndromes
      • ADH
      • Hypercalcemia
  • Nonepithelial tumors
    • Rare
    • Leiomyosarcomas
      • Most common
      • 25% present with metastases
      • Interlacing bundles of spindle-shaped cells
      • Less aggressive
      • Fewer mitotic figures
      • More favorable than that of squamous cell carcinoma
    • In patients with Kaposi's sarcoma, gastrointestinal involvement of the esophagus can be seen
  • Malignant melanoma
    • Rare
    • Mean survival —> 7 months
  • Lymphoma
    • 1% of esophageal malignancies

Prognostic Factors

  • Stage is the most important prognostic factor
    • Increasing depth of penetration (T stage)
    • Nodal involvement (N stage)
    • Absence or presence of distant metastases (M stage)
  • Tumor location
    • Middle and lower third —> more localized (25-50%)
    • Upper third —> less localized (10-25%)
  • Tumor size
    • >5cm ==> ~75% metastatic
  • Resection margin
  • Histology
    • Adenoca better than SCC
    • 5-yr OS: 47% for adenoca vs 37% with SCC
  • Women better than men
  • Higher survival rates in Caucasians than African Americans
  • Age
    • >65yrs
  • Weight loss
  • Performance status
  • Deep ulceration of the tumor
  • Sinus tract formation
  • Fistula formation
  • LVI

Management of Esophageal Ca