45. Oesophageal carcinoma

1. Definition

• Oesophageal carcinoma → malignant epithelial tumour of the oesophagus
• Two main types → squamous cell carcinoma (SCC) and adenocarcinoma
• Oesophagogastric junction (OGJ) tumour → centre within 2 cm of the junction; staged as oesophageal cancer

2. Epidemiology

• About the 7th most common cancer and 6th cause of cancer death worldwide
• SCC → most common type worldwide; "oesophageal cancer belt" from Iran to China
• Adenocarcinoma → most common type in the UK, USA and Western Europe; rising fast
• Men more than women → adenocarcinoma 5:1, SCC 3:1
• Age 60–70 years
• Most present late; 5-year survival about 20%

3. Aetiology and risk factors

Squamous cell carcinoma

• Smoking and alcohol → synergistic
• Hot drinks, nitrosamines, poor diet (low fruit and vegetables)
• Achalasia, caustic stricture
• Plummer-Vinson syndrome (iron deficiency, web)
• Tylosis (inherited palmar hyperkeratosis)
• Head and neck cancer, previous radiotherapy

Adenocarcinoma

• GORD → Barrett's oesophagus
• Obesity (central)
• Smoking
• Male sex, white ethnicity
• Helicobacter pylori → may protect

4. Pathogenesis

Adenocarcinoma

1. Chronic reflux injures the squamous lining
2. Intestinal metaplasia → Barrett's oesophagus (columnar lining with goblet cells)
3. Low-grade dysplasia → high-grade dysplasia (HGD) → invasive adenocarcinoma
4. Risk about 0.3% a year in non-dysplastic Barrett's; much higher with HGD

SCC

• Chronic irritation → squamous dysplasia → carcinoma; often multifocal ("field change")

Site

• SCC → upper and middle thirds
• Adenocarcinoma → lower third and OGJ

Spread

• Local → no serosa, so early spread to trachea, bronchus, aorta, recurrent laryngeal nerve, pericardium
• Lymphatic → rich submucosal lymphatics; skip lesions; nodes in neck, chest and abdomen (coeliac)
• Blood → liver, lung, bone, brain
• Peritoneum → OGJ tumours

5. Classification

Histology

• SCC
• Adenocarcinoma
• Rare → small cell carcinoma, melanoma, gastrointestinal stromal tumour (GIST), leiomyosarcoma
• Benign tumours → leiomyoma (most common), lipoma, polyps, granular cell tumour

TNM (AJCC 8th edition)

• Tis → HGD
• T1a → lamina propria or muscularis mucosae; T1b → submucosa
• T2 → muscularis propria
• T3 → adventitia
• T4a → pleura, pericardium, azygos vein, diaphragm, peritoneum (resectable); T4b → aorta, vertebra, trachea (unresectable)
• N1 1–2 nodes, N2 3–6, N3 ≥ 7
• M1 → distant metastases

Siewert (OGJ adenocarcinoma)

• Type I → centre 1–5 cm above the OGJ (distal oesophagus)
• Type II → 1 cm above to 2 cm below (true cardia)
• Type III → 2–5 cm below (subcardial stomach)

6. Clinical picture

Symptoms

• Progressive dysphagia → solids, then soft food, then liquids
• Weight loss, anorexia
• Odynophagia, retrosternal pain
• Regurgitation, cough on swallowing (tracheo-oesophageal fistula)
• Hoarseness → recurrent laryngeal nerve invasion
• Haematemesis, anaemia
• Early cancer → dyspepsia only, or found on Barrett's surveillance
• Red flag → new dysphagia at any age, or dyspepsia with weight loss over 55, needs urgent endoscopy (2-week wait)

Signs

• Often none
• Cachexia
• Supraclavicular node (Virchow's node, left)
• Hepatomegaly, ascites
• Horner's syndrome (rare)

7. Diagnosis

Endoscopy

• Upper GI endoscopy with multiple biopsies → test of choice
• Distance from incisors, length, relation to OGJ, Barrett's segment
• HER2 and PD-L1 testing on tissue (adenocarcinoma)

Staging

1. CT chest, abdomen and pelvis with contrast → metastases, local invasion
2. PET-CT → if curative treatment is planned; finds hidden metastases
3. Endoscopic ultrasound (EUS) → T and N stage; fine-needle aspiration of nodes
4. Staging laparoscopy → OGJ and Siewert II–III tumours; peritoneal spread
5. Bronchoscopy → upper and middle third tumours near the airway
6. Barium swallow → "apple core" or shouldered stricture; less used now

Fitness

• Performance status, cardiopulmonary exercise testing, spirometry, nutrition
• Decision by the upper GI MDT

8. Differential diagnosis

• Benign peptic stricture
• Achalasia and pseudoachalasia
• Leiomyoma, GIST
• External compression → lung cancer, nodes, aortic aneurysm
• Gastric cancer of the cardia

9. Treatment

Surgical

• Early disease (HGD, T1a) → endoscopic resection (EMR or ESD) + radiofrequency ablation of remaining Barrett's; cure rate > 90%
• T1b–T2 N0 → oesophagectomy (some T1b by endoscopy if low risk)
• Locally advanced (T3–T4a or N+) → neoadjuvant therapy, then oesophagectomy:
  • Adenocarcinoma → perioperative FLOT chemotherapy (FLOT4; ESOPEC 2024 favoured it over CROSS)
  • SCC → neoadjuvant chemoradiotherapy (CROSS); complete response in about half of SCC
  • Residual disease after CROSS → adjuvant nivolumab (CheckMate 577)
• Oesophagectomy → main types:
  • Ivor Lewis → laparotomy (or laparoscopy) + right thoracotomy; anastomosis in the upper chest; lower and middle third tumours
  • McKeown (three-stage) → right thoracotomy + abdomen + neck anastomosis; upper and middle third tumours
  • Transhiatal → abdomen + neck, no thoracotomy; fewer lung problems, less node clearance
  • Left thoracoabdominal → OGJ tumours
  • Minimally invasive or robotic → fewer lung complications
• Principles:
  • Margins → 5–10 cm proximal, 5 cm distal (longitudinal submucosal spread)
  • Two-field lymphadenectomy (abdominal and thoracic)
  • Conduit → stomach (gastric tube) on the right gastroepiploic artery; colon or jejunum if the stomach cannot be used
  • Pyloric drainage, feeding jejunostomy
  • Enhanced recovery, high-volume centres
• Operative mortality → 2–5% in high-volume centres

Conservative

• Definitive chemoradiotherapy → SCC of the cervical oesophagus, or patients unfit for or refusing surgery
• Palliation (most patients):
  • Self-expanding metal stent → fast relief of dysphagia; covered stent seals a TOF
  • Palliative radiotherapy, brachytherapy
  • Chemotherapy ± trastuzumab (HER2+) or immunotherapy (nivolumab, pembrolizumab)
  • Nutrition, dietitian, analgesia
  • Laser, argon plasma or photodynamic therapy for unfit patients
• Barrett's surveillance → endoscopy every 2–5 years; HGD treated by endoscopy

10. Complications

Of disease

• Malnutrition, aspiration pneumonia
• Tracheo-oesophageal fistula
• Bleeding, aorto-oesophageal fistula
• Recurrent laryngeal nerve palsy

Of oesophagectomy

• Pneumonia, respiratory failure → most common
• Anastomotic leak (5–15%) → neck leaks are easier to treat than chest leaks
• Conduit necrosis
• Atrial fibrillation
• Chylothorax (thoracic duct injury)
• Recurrent laryngeal nerve injury (neck anastomosis)
• Anastomotic stricture, reflux, delayed gastric emptying, dumping

11. Prognosis

• 5-year survival about 20% for all patients
• After neoadjuvant therapy and resection → about 45–50%
• T1a after endoscopic resection → > 90%
• Stage IV → median survival about 1 year with modern systemic therapy