What are the types of oesophageal cancer and where do they occur?
Oesophageal cancers are grouped by histology into squamous cell carcinoma (SCC) and adenocarcinoma. Worldwide SCC predominates, especially in the 'oesophageal cancer belt' (northern Iran, southern Russia, central Asia and northern China), where it accounts for about 90% of cases. In Western countries SCC has been falling while adenocarcinoma has risen sharply, parallel with the rise of GERD and obesity.
| Feature | Squamous cell carcinoma | Adenocarcinoma |
|---|---|---|
| Usual site | Mostly upper and middle oesophagus (about 58% middle thoracic, 10% upper thoracic, about 32% lower thoracic) | Lower third and gastro-oesophageal junction (about 96% in the lower oesophagus) |
| Precursor | Squamous dysplasia | Barrett's oesophagus (intestinal metaplasia) |
| Risk factors | Smoking, alcohol, hot beverages, poor diet, achalasia, caustic injury, tylosis, Plummer-Vinson syndrome, HPV, previous head and neck SCC | Chronic GERD, Barrett's, obesity, smoking, male sex, white race; alcohol is not a risk factor |
| Trend | Falling in developed countries; dominant in developing regions | Rising in the Western world |
| Other epidemiology | Linked to low economic status and lack of refrigeration (nitrosamine exposure from cured meat) | Strong male predominance (about 9:1 male to female) |
What is Barrett's oesophagus?
Barrett's oesophagus is a premalignant condition: salmon-coloured mucosa extending at least 1 cm above the gastro-oesophageal junction (top of the gastric folds), with biopsies showing columnar epithelium with goblet cells (intestinal metaplasia). It is acquired, usually from long-standing GERD, and is found in 5% to 12% of patients with chronic reflux symptoms. It is the only known endoscopically identifiable precursor of oesophageal adenocarcinoma.
Chronic acid and bile exposure inflames the squamous epithelium and, through intestinal differentiation factors (CDX2, MUC2), replaces it with intestinal-type columnar cells. Early molecular changes include CDX2 and TP53 mutations, and up to 90% of patients show a clonal abnormality of the p16 tumour suppressor gene.
| Risk factor | Notes |
|---|---|
| Chronic GERD | Present in most patients |
| Male sex, white race, age over 50 | Barrett's is about twice as common in men; adenocarcinoma about 9 times |
| Central obesity, smoking | Added risk |
| Family history | First-degree relative with Barrett's or oesophageal adenocarcinoma |
How is Barrett's diagnosed, graded and kept under surveillance?
Upper GI endoscopy with forceps biopsy is the gold-standard test. Diagnosis needs at least 1 cm of columnar-lined oesophagus with intestinal metaplasia (goblet cells) on biopsy. The British Society of Gastroenterology and Japanese guidelines do not insist on goblet cells. The ACG (2022) advises screening in people with chronic GERD symptoms plus at least 3 other risk factors (male sex, age over 50, white race, smoking, central obesity, family history).
- Biopsy protocol: at least 8 biopsies (2 per quadrant) at 2 cm intervals for short segments. Seattle protocol for segments over 4 cm: four-quadrant biopsies every 2 cm (every 1 cm if dysplasia is known or suspected). Visible lesions are biopsied first; exophytic lesions are endoscopically resected.
- Prague criteria: C = circumferential extent and M = maximal extent above the gastric folds. A circumferential 6 cm and maximal 8 cm segment is C6M8. Islands of metaplasia are ignored.
- Dysplasia: intestinal-type is graded low-grade or high-grade. Diagnosis of dysplasia should be confirmed by a second expert pathologist. High-grade dysplasia and intramucosal carcinoma are hard to tell apart (observer variability).
- Acid suppression: long-term PPI is advised in all Barrett's patients, with a possible chemopreventive effect.
| Histology | Annual cancer risk | Management |
|---|---|---|
| No dysplasia | 0.1% to 0.5% per year | Endoscopy every 5 years if segment under 3 cm; every 3 years if 3 cm or longer |
| Indefinite dysplasia | - | Repeat endoscopy in 6 months on twice-daily PPI; if unchanged, then annually |
| Low-grade dysplasia | Variable, 1% to 43% per year | Endoscopic eradication therapy (EET); if declined, repeat at 6 and 12 months, then annually |
| High-grade dysplasia | 23% to 60% per year | EET (esophagectomy no longer first choice); surgery for poor prognostic features or submucosal invasion |
How is Barrett's with dysplasia treated?
Endoscopic eradication therapy (EET) treats low-grade dysplasia, high-grade dysplasia and early adenocarcinoma, and is preferable to surveillance with acid suppression alone. It combines resection of visible lesions with ablation of the remaining Barrett's mucosa.
| Technique | Use and complications |
|---|---|
| Radiofrequency ablation (RFA) | Preferred ablation for flat dysplasia, usually 3 to 4 sessions. Chest pain up to 14 days; strictures, perforation, bleeding less commonly |
| Cryotherapy | Liquid nitrogen spray or balloon cryoablation |
| Hybrid argon plasma coagulation | Small islands; high stricture rate if used circumferentially |
| EMR / ESD | For nodules or masses; EMR for small, superficial neoplasia, ESD for larger lesions or when T1b invasion is suspected; ablation of the remainder follows |
What are the clinical features and how is oesophageal cancer diagnosed?
Early disease is silent. The classic presentation is progressive dysphagia, first to solids then to liquids, with weight loss; odynophagia, chest pain (mid or lower tumours), anaemia from chronic blood loss and hoarseness (recurrent laryngeal nerve invasion) indicate advanced disease. Examination may show cachexia, supraclavicular or cervical nodes, hepatomegaly (metastases) and iron-deficiency anaemia.
- Upper GI endoscopy with biopsy - histological diagnosis.
- CT chest, abdomen and pelvis - extent and distant metastases.
- Endoscopic ultrasound (EUS) - depth of invasion (T stage) and nodal biopsy if no metastases.
- PET scan - lymph nodes and occult metastases.
- Diagnostic laparoscopy - for distal junctional tumours and cardia tumours of stage III or node-positive, to find occult peritoneal disease.
Staging follows the AJCC 8th edition, with separate systems for SCC and for oesophageal and junctional adenocarcinoma, and separate clinical (cTNM), post-neoadjuvant (ypTNM) and pathological stages. Common sites of spread are liver, lungs, distant lymph nodes, bones and peritoneum; peritoneal carcinomatosis occurs in about 10% to 15% of junctional adenocarcinomas, especially signet-ring types.
How is oesophageal cancer treated?
Treatment depends on accurate pre-treatment staging. About 22% of cases are localised and resectable and a further 30% have regional nodes.
| Disease | Treatment |
|---|---|
| Superficial (lamina propria or muscularis mucosae) | Endoscopic resection (EMR, ESD) with or without ablation |
| T1bN0, low risk, well differentiated, under 3 cm | Esophagectomy with lymphadenectomy |
| T2 node-positive, T3, selected T4a | Neoadjuvant chemoradiation then esophagectomy (CROSS regimen: carboplatin and paclitaxel with 41.4 Gy) |
| Unresectable T4b, or surgery declined | Definitive chemoradiation (cisplatin and 5-FU with 50 Gy, from RTOG 85-01) |
| Metastatic | Palliative systemic therapy; stents, laser, dilation or feeding tube for dysphagia |
- Surgical approaches for middle and lower thoracic tumours: transhiatal, transthoracic (Ivor-Lewis) and tri-incisional. Cervical tumours need partial removal of larynx, pharynx and thyroid; junctional tumours need total oesophagectomy with partial gastrectomy.
- Lymph nodes: at least 15 nodes should be resected for adequate staging; survival rises with the number resected.
- CROSS trial: neoadjuvant chemoradiation gave R0 resection in 92%, pathological complete response 29% (49% in SCC, 23% in adenocarcinoma), and 5-year survival 47% vs 34% with surgery alone.
- A positive circumferential resection margin raises the odds of mortality about four-fold (OR 4.02).
- Metastatic disease to other organs or non-regional nodes is an absolute contraindication to esophagectomy.
For the acute complication of oesophageal rupture see Boerhaave syndrome, and for downstream nutritional consequences of gastric surgery see post-gastrectomy syndromes.
What are the common exam traps?
- Commonest oesophageal cancer worldwide: SCC; commonest in the West now: adenocarcinoma. Do not mix up the site: SCC mid-oesophagus, adenocarcinoma lower third.
- Barrett's = intestinal metaplasia with goblet cells, at least 1 cm; it is metaplasia, not dysplasia, and not itself malignant.
- Alcohol is a risk factor for SCC, not for adenocarcinoma.
- Prague criteria C and M express circumferential and maximal length.
- Gold standard for Barrett's: endoscopy with biopsy (Seattle protocol).
- Surveillance interval without dysplasia: 5 years if under 3 cm, 3 years if 3 cm or more.
- Preferred ablation for flat dysplasia: radiofrequency ablation. Nodule: EMR or ESD first.
- Neoadjuvant chemoradiation (CROSS) is the standard for T2 node-positive and T3 resectable tumours.
Practise in the NEET PG Surgery PYQs, the INI-CET PYQs and the most repeated topics.