Special Surgery 6. Malignant Diseases of the Esophagus: Diagnosis and Treatment

I. Definition, Risk Factors and Types

Definition and Epidemiology

• Esophageal cancer: Malignant tumor of the esophagus
• Main types: squamous cell carcinoma (SCC) and adenocarcinoma (ACC)
• Peak incidence: 60-70 years
• Male predominance
• Often diagnosed late because dysphagia appears after marked luminal narrowing
• Prognosis: generally poor; better in early-stage disease with multimodal treatment

Risk Factors

• Alcohol
• Smoking
• Hot drinks / thermal injury
• Barrett esophagus, chronic GERD
• Obesity: mainly adenocarcinoma risk
• Corrosive / caustic injury
• Achalasia, long-standing diverticulum with stasis
• Diet poor in fruits/vegetables, nitrosamines
• Plummer-Vinson syndrome: SCC risk

Main Types

1. Adenocarcinoma
2. Squamous cell carcinoma

1. Adenocarcinoma (ACC)

• Arises from glandular epithelium, usually on Barrett esophagus background
• Typical location: lower third / gastroesophageal junction
• Male predominance; increasing in Western countries
• Associated with GERD, Barrett esophagus, obesity and nitrosamines

2. Squamous Cell Carcinoma (SCC)

• Arises from squamous epithelium
• Typical location: upper and middle third; can occur anywhere in squamous mucosa
• More common worldwide; high-incidence regions include East Asia and parts of Africa
• Associated with smoking, alcohol, achalasia, caustic injury, poor diet and Plummer-Vinson syndrome
• Exam note: SCC often has worse prognosis, but stage and resectability are most important

II. Clinical Features and Diagnosis

Clinical Features

• Progressive dysphagia: solids → liquids
• Weight loss, anorexia, cachexia
• Odynophagia
• Regurgitation, aspiration
• Retrosternal/chest pain or back pain: advanced disease
• Upper GI bleeding/anemia can occur
• Symptoms due to local invasion:

• Dysphonia/hoarseness → recurrent laryngeal nerve palsy
• Cough during swallowing → tracheo-esophageal fistula
• Cough, hemoptysis → tracheobronchial invasion
• Back pain → posterior invasion / vertebral involvement

Diagnosis

1. Upper endoscopy with biopsy
2. Barium swallow
3. Staging investigations

1. Upper Endoscopy with Biopsy

• Gold standard diagnostic test
• Direct visualization + multiple biopsies → histological diagnosis
• Defines tumor level, obstruction and relation to EGJ/stomach

2. Barium Swallow

• Irregular narrowing / shouldering / apple-core lesion
• Useful if endoscopy is difficult or fistula/perforation anatomy is suspected
• Does not replace biopsy

3. Staging Investigations

• CT chest-abdomen-pelvis: local spread, lymph nodes, liver/lung metastases, relation to aorta/airway
• PET-CT: occult distant metastases before curative-intent treatment
• Endoscopic ultrasound (EUS): best for T depth and regional N staging if scope can pass

• EUS is not the main distant-metastasis test
• EUS-guided FNA can sample suspicious nodes

• Bronchoscopy: upper/middle tumors, cough, hemoptysis, suspected airway invasion/fistula
• Laryngoscopy: hoarseness or suspected recurrent laryngeal nerve palsy
• Diagnostic laparoscopy: selected distal/GEJ adenocarcinoma if occult peritoneal disease is possible

III. Staging, Resectability and Preoperative Logic

TNM Staging

1. T: Tumor Depth

• Tis: high-grade dysplasia / carcinoma in situ
• T1a: lamina propria or muscularis mucosae
• T1b: submucosa
• T2: muscularis propria
• T3: adventitia
• T4: adjacent organs/structures

• T4a: potentially resectable invasion, e.g. pleura, pericardium, diaphragm, azygos vein
• T4b: usually unresectable invasion, e.g. aorta, vertebral body, trachea/main bronchus

2. N: Regional Lymph Nodes

• N0: no regional lymph node metastasis
• N1: 1-2 positive nodes
• N2: 3-6 positive nodes
• N3: 7 or more positive nodes

3. M: Distant Metastasis

• M0: no distant metastasis
• M1: distant metastasis
• Common sites: liver, lung, distant lymph nodes, bone, peritoneum

Resectability and Operability

• Resectable disease: no distant metastasis + no unresectable T4b invasion + R0 resection seems possible
• Unresectable / non-curative situation:

• Distant metastasis: liver, lung, bone, peritoneum, distant non-regional nodes
• T4b invasion: aorta, vertebral body, trachea/main bronchus, extensive mediastinal fixation

• Operability: patient fitness for major surgery

• Nutritional status, weight loss, sarcopenia
• Performance status/frailty
• Cardiorespiratory reserve and anesthetic risk

• Onco-team decides sequence: endoscopy/radiology/pathology + surgery + oncology + radiotherapy + nutrition

IV. Treatment

General Principles

• Treatment depends on histology, tumor level, TNM stage, resectability, operability and nutrition
• Early mucosal disease → endoscopic treatment may be curative
• Most locally advanced resectable tumors → multimodal treatment
• Metastatic/unresectable disease → palliation + systemic therapy

1. Intramucosal / Early Tumors

• Endoscopic mucosal resection (EMR)
• Endoscopic submucosal dissection (ESD)
• Best candidates: Tis/T1a, small lesion, good/moderate differentiation, no lymphovascular invasion, no suspicious nodes
• Esophagectomy or oncological treatment if high-risk features:

• Large tumor, poor differentiation
• T1b submucosal invasion
• Lymphovascular invasion or suspicious lymph nodes
• Incomplete resection / positive deep margin

2. Locally Advanced, Resectable Tumors

• Usually T2-T3 and/or node-positive disease
• Standard logic: neoadjuvant treatment → restaging → esophagectomy + lymphadenectomy if still resectable and patient fit
• Neoadjuvant chemoradiotherapy: common for SCC and many esophageal cancers; improves R0 rate and survival
• Perioperative chemotherapy: important option for distal esophageal/GEJ adenocarcinoma in European practice
• Operation: esophagectomy + regional lymphadenectomy + reconstruction, usually gastric conduit
• Goal: R0 resection + adequate lymph node clearance

3. Surgical Approaches

• Transhiatal esophagectomy:

• Neck + abdominal incisions
• No thoracotomy
• Limited mediastinal lymphadenectomy; not literally no lymph node removal
• Cervical anastomosis

• Transthoracic esophagectomy / Ivor Lewis:

• Right chest + abdominal incisions
• Intrathoracic esophagogastric anastomosis
• Good mediastinal lymphadenectomy
• Common for middle/lower thoracic and GEJ tumors

• Three-incision / McKeown esophagectomy:

• Neck + right chest + abdominal incisions
• Cervical anastomosis
• Useful for higher tumors where proximal margin is important

4. Definitive Chemoradiotherapy

• Curative-intent treatment without planned surgery
• Indications: medically inoperable patient, unresectable localized tumor without metastasis, cervical esophageal cancer, selected SCC for organ preservation
• Requires close follow-up; salvage surgery only in selected fit patients

5. Metastatic / Irresectable Tumors: Palliative Therapy

• Goals: relieve dysphagia, maintain nutrition, control symptoms, prolong survival if possible
• Severe dysphagia:

• Endoscopic dilatation in selected strictures
• Self-expanding metal stent (SEMS)
• Palliative radiotherapy/chemoradiotherapy
• Feeding access: jejunostomy often preferred if stomach may be needed as conduit; PEG/gastrostomy only in selected palliative cases

• Systemic treatment: chemotherapy, immunotherapy/chemoimmunotherapy, radiotherapy according to histology and protocol
• HER2-targeted therapy can be used for HER2-positive metastatic adenocarcinoma when indicated
• Complications: fistula, bleeding, pain → stent/radiotherapy/endoscopic or palliative-care measures depending on problem