WebDoctor Encyclopedia

Gastrointestinal

Oesophagus

Encyclopedia entries in Oesophagus.

  1. Oesophagus

    Oesophageal adenocarcinoma

    Oesophageal adenocarcinoma arises in the lower oesophagus, usually after Barrett’s. This entry covers GORD, staging, and perioperative treatment.

    5,596 words

  2. Oesophagus

    Oesophageal squamous cell carcinoma

    Oesophageal squamous cell carcinoma arises from the squamous lining, often mid/upper oesophagus. This entry covers smoking, alcohol, and chemoradiation.

    4,984 words

Oesophageal cancer is the 7th most common cancer and the 6th leading cause of cancer death globally. It is characterized by two distinct histological entities—squamous cell carcinoma (SCC) and adenocarcinoma (AC)—with divergent epidemiologies, risk factors, and anatomical distributions. Despite advances in endoscopic resection, neoadjuvant therapy, and minimally invasive surgery, 5-year overall survival remains approximately 20–25%. This review summarizes current guidelines for screening, staging, and stage-directed multimodal management.

1. Epidemiology & Aetiology: A Tale of Two Diseases

Feature Squamous Cell Carcinoma (SCC) Adenocarcinoma (AC)
Global Incidence Predominant worldwide (90% of cases); high in “Asian Belt” (China, Iran), East Africa. Rising rapidly in Western nations; now >50% of cases in US/UK.
Anatomical Site Upper & Middle third (proximal 2/3). Distal third & Gastroesophageal Junction (GEJ/Siewert I/II).
Key Risk Factors Tobacco, Alcohol (synergistic), Achalasia, Tylosis, Caustic injury, Hot beverages (>60°C), HPV (controversial), Nutritional deficiencies. GERD/Barrett’s Oesophagus (major), Obesity (central adiposity), Tobacco, Male sex. Protective: H. pylori (cagA+), NSAIDs/Statins (observational).
Precursor Lesion Dysplasia (Low/High grade) → Carcinoma in situ. Barrett’s Oesophagus (Intestinal metaplasia) → Low-grade dysplasia (LGD) → High-grade dysplasia (HGD) → Intramucosal carcinoma.

Clinical Pearl: Siewert Classification for GEJ tumours dictates surgical approach:

  • Type I: Distal oesophagus (distal to GEJ) → Treat as oesophageal cancer.
  • Type II: True cardia (1cm above – 2cm below GEJ) → Treat as oesophageal cancer.
  • Type III: Subcardial (2–5cm below GEJ) → Treat as gastric cancer.

2. Clinical Presentation

Most patients present with advanced disease (dysphagia typically occurs when luminal diameter <13mm).

  • Progressive Dysphagia: Solids → Liquids (hallmark).
  • Odynophagia: Suggests local invasion/ulceration.
  • Weight Loss & Anorexia: >10% body weight = poor prognostic sign.
  • Atypical: Hoarseness (RLN palsy), Hiccups (phrenic nerve), Tracheoesophageal fistula (cough on swallowing), Metastatic symptoms (liver, lung, bone, supraclavicular nodes/Virchow’s node).

Red Flags for Urgent Endoscopy: New-onset dysphagia >55 yrs, unexplained weight loss + upper GI symptoms, persistent vomiting, iron deficiency anaemia (males/post-menopausal females).

3. Diagnostic Workup & Staging (AJCC 8th Ed. / TNM)

A. Tissue Diagnosis

  • Upper GI Endoscopy (EGD) with Biopsy: Gold standard. Minimum 6–8 biopsies (4 quadrants x 2 levels) + brush cytology.
  • Advanced Imaging: Narrow Band Imaging (NBI), Chromoscopy (Lugol’s iodine for SCC, Acetic acid/Indigo carmine for Barrett’s) improves detection of dysplasia/early cancer.

B. Local Staging (T & N Stage)

Modality Role Accuracy
Endoscopic Ultrasound (EUS) Gold standard for T-stage (depth) & N-stage. Allows FNA of suspicious nodes. T-stage: 80-90%; N-stage: 70-80% (CT/PET better for distant mets).
Contrast-Enhanced CT Chest/Abdomen/Pelvis Baseline for distant mets (M-stage), resectability assessment (aortic/tracheal invasion). Poor for T1/T2 differentiation.
PET-CT (FDG) Standard for M-staging. Detects occult distant mets (10-15% upstaging). Assesses metabolic response to neoadjuvant therapy. Low spatial resolution; false +ve in inflammation.

C. Staging Laparoscopy

  • Indicated for locally advanced (T3/T4 or N+) AC and GEJ tumours (Siewert II/III) to detect occult peritoneal carcinomatosis (15-20% yield) before committing to neoadjuvant therapy/surgery.

D. HER2 Testing (Mandatory for Metastatic/Unresectable AC)

  • IHC 3+ or IHC 2+/FISH+ → Eligible for Trastuzumab + Chemotherapy (ToGA regimen).
  • Not indicated for SCC.

E. Biomarkers (Emerging)

  • PD-L1 (CPS ≥ 10): Predicts benefit from Pembrolizumab/Nivolumab in 1L metastatic (KEYNOTE-590, CheckMate 648) and adjuvant settings (CheckMate 577).
  • MSI-H/dMMR: Rare (~2-3% AC); indicates immunotherapy eligibility.
  • ctDNA: Prognostic post-surgery; guides adjuvant therapy escalation/de-escalation (clinical trials ongoing).

4. Management by Stage & Histology

Multidisciplinary Tumour Board (MDT) discussion is mandatory for all non-metastatic cases.

Stage 0 / Tis (High-Grade Dysplasia / Intramucosal Carcinoma)

  • Endoscopic Eradication Therapy (EET):
    • Endoscopic Mucosal Resection (EMR): Visible lesions/nodules (diagnostic + therapeutic).
    • Endoscopic Submucosal Dissection (ESD): Preferred for lesions >2cm, fibrotic, or suspected sm1 invasion (en-bloc R0 resection).
    • Radiofrequency Ablation (RFA) / Cryotherapy: Ablation of residual flat Barrett’s/HGD post-EMR.
  • Surveillance: Intensive (3-6 mo initially) per ASGE/BCSG guidelines.

T1a (Mucosal) – No Lymphovascular Invasion (LVI), Well/Mod Differentiated

  • Endoscopic Resection (ESD preferred) curative if R0, <1000µm sm invasion (sm1), no LVI, G1/G2.
  • Surgery (Oesophagectomy) if high-risk features (sm2/3, LVI, G3, R1) or ESD not feasible.

T1b (Submucosal) / T2 (Muscularis Propria) / N+ (Locally Advanced Resectable)

Standard of Care: Neoadjuvant Therapy → Surgery

Histology Preferred Neoadjuvant Regimen Key Evidence
AC / GEJ (Siewert I/II) FLOT (5-FU/Leucovorin/Oxaliplatin/Docetaxel) x 4 cycles perioperatively (pre + post-op) FLOT4-AIO: Median OS 50 vs 35 mo (vs ECF/ECX). Current Global Standard.
CROSS (Carboplatin/Paclitaxel + 41.4 Gy RT) CROSS Trial: Pathologic Complete Response (pCR) 23% (AC), 49% (SCC). Preferred if concern for local control/positive margins.
SCC CROSS (Chemoradiation) NeoRes I / JCOG1109: Neoadjuvant Chemo (FP/DC) non-inferior to CRT for SCC? Controversial. CROSS remains standard in West; Neoadj Chemo standard in Asia (JCOG9907).
Definitive Chemoradiation (dCRT) Option for unresectable, cervical oesophagus, or patient refusal/unfit for surgery. Equivalent OS to trimodal in SCC (RTOG 8501, FFCD 9102), but higher local failure. Salvage surgery morbid.

Surgical Technique

  • Approach: Minimally Invasive Oesophagectomy (MIE – Thoracoscopic/Laparoscopic ± Robotic) = Standard of Care (TIME, ROMIO, MIRO trials: reduced pulmonary complications, equivalent oncologic outcomes).
  • Reconstruction: Gastric conduit (standard); Colon/Jejunum if stomach unavailable.
  • Anastomosis: Intrathoracic (Ivor Lewis/McKeown) vs Cervical (McKeown). Intrathoracic preferred for lower anastomotic leak severity; Cervical for proximal tumours.
  • Lymphadenectomy: 2-field (Mediastinal + Abdominal) standard. 3-field (add Cervical) for upper/mid SCC (improved staging, survival benefit debated, higher RLN palsy).

Adjuvant / Post-Operative Therapy

  1. Complete Neoadjuvant FLOT (AC): Complete remaining cycles post-op (total 8 cycles).
  2. Adjuvant Nivolumab (CheckMate 577): Indicated for AC/SCC (pN+ or R1) after Neoadjuvant CRT (CROSS) + Surgery. 1 year therapy. DFS benefit (22.4 vs 11.0 mo). Not indicated if FLOT used neoadjuvantly (no trial data).
  3. Adjuvant Chemoradiation (INT-0116 / ARTIST II): Historical control for upfront surgery patients (rare now). Not standard if neoadjuvant given.

Metastatic / Unresectable Disease (Stage IV)

  • 1st Line AC (HER2+): FOLFOX/CAPOX + Trastuzumab (+ Pembrolizumab if PD-L1 CPS ≥10 – KEYNOTE-811).
  • 1st Line AC (HER2-): FOLFOX/CAPOX + Nivolumab (CheckMate 649) or Pembrolizumab (KEYNOTE-590/859) if PD-L1 CPS ≥10 (or ≥1 for Pembro). Chemo alone if CPS <1/10.
  • 1st Line SCC: Cisplatin/5-FU (or Paclitaxel) + Pembrolizumab (KEYNOTE-590) or Nivolumab (CheckMate 648) regardless of PD-L1 (Nivo+Ipi also approved).
  • 2nd Line+:
    • Ramucirumab + Paclitaxel (RAINBOW) – AC standard.
    • Trastuzumab Deruxtecan (T-DXd) – New Standard for HER2+ AC post-Trastuzumab (DESTINY-Gastric01/02).
    • Pembrolizumab/Nivolumab – If MSI-H/dMMR or high TMB.
    • Clinical Trials: Claudin 18.2 (Zolbetuximab – SPOTLIGHT/GLOW), FGFR2b, KRAS G12C.

5. Management of Complications

Complication Management
Anastomotic Leak Contained/Stable: NPO, antibiotics, drainage (Endoscopic vac/stent/CT-guided), TPN/NJ feed. Unstable/Septic: Re-laparotomy/thoracotomy, diversion (cervical esophagostomy).
Stricture (Benign) Endoscopic dilation (bougie/balloon). Refractory: Steroid injection, Stent (temp), Incisional therapy.
Malignant Dysphagia (Palliation) Self-Expanding Metal Stents (SEMS) – Immediate relief. EBRT/Brachytherapy – Durable relief. Laser/APC – Debulking. Nutrition: PEG/Jejunostomy if stent fails/bridging.
Tracheoesophageal Fistula Covered SEMS (dual stenting oesophagus + trachea often needed). Palliative.
Chylothorax Conservative (NPO, TPN, Octreotide, Pleural drainage) → Surgical ligation (thoracoscopic) if >1L/day or persistent >5-7 days.

6. Surveillance & Survivorship

  • High Risk of Recurrence: Peak 2-3 years post-op.
  • Schedule (NCCN/ESMO):
    • Years 1-2: q3-6 months (History, Exam, Labs, CT Chest/Abd/Pelvis).
    • Years 3-5: q6-12 months.
    • Endoscopy: Annually (screen for metachronous gastric cancer, Barrett’s surveillance, anastomotic stricture).
  • Quality of Life Focus: Dumping syndrome, reflux (head elevation, PPI), nutritional support (small frequent meals, pancreatic enzymes), vocal cord palsy (speech therapy), psychological support.

7. Key Takeaways for the Clinician

  1. Histology dictates everything: SCC vs AC have different risk factors, staging nuances, and neoadjuvant standards.
  2. Early Detection = Cure: Endoscopic resection (ESD/EMR) for T1a is curative with organ preservation. Screen high-risk Barrett’s (Prague C&M criteria).
  3. Trimodal Therapy is Standard: Neoadjuvant FLOT (AC) or CROSS (SCC/AC) + MIE offers best survival for locally advanced disease.
  4. Adjuvant Nivolumab: Practice-changing for residual disease post-CROSS + Surgery.
  5. Biomarker-Driven Metastatic Care: HER2, PD-L1, MSI, Claudin 18.2 testing mandatory at diagnosis of Stage IV.
  6. Centralization Matters: High-volume centres (>20 resections/yr) have significantly lower mortality (1-3% vs 5-10%) and better long-term survival.

References

  1. AJCC Cancer Staging Manual, 8th Edition.
  2. NCCN Guidelines v.2.2024: Esophageal and Esophagogastric Junction Cancers.
  3. ESMO Clinical Practice Guidelines: Oesophageal Cancer (2023/2024 updates).
  4. FLOT4-AIO Trial: Al-Batran et al. Lancet Oncol 2019 / J Clin Oncol 2023 (OS update).
  5. CROSS Trial: Shapiro et al. NEJM 2012; van Hagen et al. NEJM 2012.
  6. CheckMate 577: Kelly et al. NEJM 2021 (Adjuvant Nivolumab).
  7. CheckMate 648 / KEYNOTE-590 / CheckMate 649: 1st Line Immunotherapy combinations.
  8. DESTINY-Gastric01/02: Shitara et al. NEJM 2020 / Lancet 2022 (T-DXd).
  9. SPOTLIGHT / GLOW: Shah et al. Lancet 2023 / Janjigian et al. Lancet 2023 (Zolbetuximab).
  10. TIME / ROMIO / MIRO Trials: Minimally Invasive Oesophagectomy evidence.

Disclaimer: This article is for educational purposes only and does not constitute individual medical advice. Treatment decisions must be individualized by a multidisciplinary team based on current guidelines, patient comorbidities, and patient preference.