Special Surgery 6. Malignant Diseases of the Esophagus, Diagnosis, Treatment

I. Definition, Epidemiology and Risk Factors

Definition

Malignant tumor of the esophagus
Main histological types: squamous cell carcinoma (SCC) and adenocarcinoma (ACC)
Often presents late because dysphagia appears after significant luminal narrowing
Prognosis is generally poor, but early mucosal disease can be curable

Epidemiology

Peak incidence: 60-70 years
Male predominance
SCC: more common worldwide; high-incidence regions include East Asia and parts of Africa
Adenocarcinoma: increasing in Western countries, especially distal esophagus / gastroesophageal junction

Risk Factors

General Risk Factors

Smoking
Alcohol
Hot drinks / thermal mucosal injury
Low fruit and vegetable intake
Corrosive / caustic injury
Achalasia
Long-standing esophageal diverticulum with stasis and chronic irritation
Previous mediastinal radiotherapy

Risk Factors by Histology

Type	Typical Location	Main Associations
Squamous cell carcinoma	Upper and middle third; can occur anywhere in squamous mucosa	Smoking, alcohol, achalasia, caustic injury, poor diet, Plummer-Vinson syndrome
Adenocarcinoma	Lower third / gastroesophageal junction	Chronic GERD, Barrett esophagus, obesity, male sex, Western diet

Pathogenesis

SCC: chronic mucosal irritation → dysplasia → invasive squamous carcinoma
Adenocarcinoma: GERD → Barrett metaplasia → dysplasia → adenocarcinoma
Local spread:

Longitudinal submucosal spread along esophageal wall
Early lymphatic spread because esophagus has rich longitudinal lymphatic drainage
Direct invasion into trachea, bronchi, aorta, pericardium, pleura or vertebral body in advanced disease

II. Types, Clinical Features and Diagnosis

Main Types

1. Squamous Cell Carcinoma (SCC)

Arises from squamous epithelium
Usually upper/middle third of esophagus
Risk factors: smoking, alcohol, achalasia, caustic injury, Plummer-Vinson syndrome
More common worldwide
Definitive chemoradiotherapy can be a curative option in selected SCC patients

2. Adenocarcinoma (ACC)

Arises from glandular epithelium, usually in Barrett esophagus
Usually lower third / gastroesophageal junction
Risk factors: chronic GERD, Barrett esophagus, obesity
Increasing in Western countries
Often treated with multimodal therapy: surgery + perioperative chemotherapy or neoadjuvant chemoradiotherapy depending on stage/location/protocol

Clinical Features

Progressive dysphagia:

Initially solids
Later liquids
Suggests mechanical narrowing

Weight loss, anorexia, cachexia
Odynophagia
Regurgitation, aspiration, aspiration pneumonia
Retrosternal pain, chest pain or back pain
Upper GI bleeding, anemia
Symptoms due to local invasion:

Dysphonia / hoarseness → recurrent laryngeal nerve palsy
Cough during swallowing → tracheo-esophageal fistula
Hemoptysis → airway invasion
Severe back pain → posterior invasion / vertebral involvement
Horner syndrome can occur with upper mediastinal invasion

Palpable supraclavicular lymph node can indicate advanced disease

Diagnosis

1. Upper Endoscopy + Biopsy

Gold standard diagnostic test
Direct visualization of tumor
Multiple biopsies confirm histology
Defines location in relation to incisors, EGJ and stomach
Assess obstruction and possibility of endoscopic passage

2. Barium Swallow

Shows irregular narrowing, shouldering / apple-core lesion, obstruction or fistula
Useful if endoscopy is difficult or perforation/fistula anatomy is suspected
Does not replace biopsy

3. Staging Investigations

CT chest, abdomen and pelvis:

Local extension, lymph nodes, liver/lung metastases
Assesses relation to aorta, airway and adjacent organs

PET-CT:

Detects occult distant metastases
Useful before curative-intent treatment

Endoscopic ultrasound (EUS):

Best for local T stage and regional lymph nodes if the scope can pass
EUS-guided FNA can sample suspicious nodes
Not the main test for distant metastasis

Bronchoscopy:

Upper/middle third tumors near tracheobronchial tree
Hoarseness, cough, suspected airway invasion or fistula

Laryngoscopy:

Hoarseness / suspected recurrent laryngeal nerve palsy
Proximal cervical esophageal tumor

Diagnostic laparoscopy can be considered for distal esophageal / GEJ adenocarcinoma when occult peritoneal disease is possible

Preoperative Assessment

Nutritional status: weight loss, albumin, sarcopenia, oral intake
Performance status and frailty
Cardiorespiratory fitness: ECG, echocardiography/stress testing if indicated, pulmonary function
Anaesthetic risk and operability must be separated from tumor resectability
Multidisciplinary onco-team decision: surgeon, oncologist, radiotherapist, gastroenterologist, radiologist, pathologist, dietitian

III. Staging and Resectability

TNM Staging

1. T: Tumor Depth

Tis: high-grade dysplasia / carcinoma in situ
T1: tumor invades lamina propria, muscularis mucosae or submucosa

T1a: lamina propria or muscularis mucosae
T1b: submucosa

T2: muscularis propria
T3: adventitia
T4: adjacent 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 regional lymph nodes
N2: 3-6 positive regional lymph nodes
N3: 7 or more positive regional lymph nodes

3. M: Distant Metastasis

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

Resectability

Resectable / Curative-Intent Disease

No distant metastasis
No unresectable T4b invasion
Patient medically fit for major surgery or definitive chemoradiotherapy
Curative treatment usually requires R0 resection or definitive oncological control

Unresectable / Non-Curative Situation

Distant metastasis: liver, lung, bone, peritoneum, distant non-regional lymph nodes
T4b invasion:

Aorta
Vertebral body
Trachea or main bronchus
Extensive mediastinal invasion where R0 resection is impossible

Medically inoperable patient can still be treated with definitive chemoradiotherapy if tumor extent allows

Prognostic Factors

Stage is the most important prognostic factor
Lymph node positivity worsens prognosis
R0 resection improves survival
Poor differentiation, lymphovascular invasion and deep submucosal invasion worsen prognosis
SCC often has worse overall prognosis in older exam notes, but outcome mainly depends on stage, location, treatment response and patient fitness

IV. Treatment

General Principles

Treatment depends on:

Histology: SCC vs adenocarcinoma
Location: cervical, upper/middle/lower thoracic, GEJ
TNM stage
Resectability and operability
Nutritional status and patient preference

Multimodal therapy is standard for most locally advanced tumors
Early mucosal lesions can be treated endoscopically in selected cases
Advanced metastatic disease → palliation, dysphagia relief and systemic therapy

1. Early / Intramucosal Tumors

Suitable for endoscopic resection when:

Tis or T1a mucosal disease
Small, well/moderately differentiated lesion
No lymphovascular invasion
No suspicious lymph nodes
Complete en bloc resection possible

Endoscopic mucosal resection (EMR)
Endoscopic submucosal dissection (ESD)
Barrett dysplasia / early adenocarcinoma: endoscopic resection + ablation of remaining Barrett mucosa when indicated
Esophagectomy or oncological treatment if high-risk features:

T1b submucosal invasion
Poor differentiation
Lymphovascular invasion
Positive vertical margin
Suspicious lymph nodes

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 resectable esophageal cancers
Improves R0 resection rate and survival compared with surgery alone in many patients

Perioperative chemotherapy:

Important option for distal esophageal / GEJ adenocarcinoma
FLOT-type regimens are commonly used in European practice for fit patients with adenocarcinoma

Operation: esophagectomy with regional lymphadenectomy and reconstruction, usually gastric conduit
Goal: R0 resection + adequate lymph node clearance

3. Surgical Approaches

Transhiatal Esophagectomy

Abdominal + cervical incisions
No thoracotomy
Blunt/limited mediastinal dissection through hiatus and neck
Lymphadenectomy is more limited than transthoracic approaches; not literally no lymph node removal
Cervical anastomosis

Transthoracic Esophagectomy: Ivor Lewis

Abdominal + right thoracic approach
Gastric conduit formation + thoracic esophageal resection
Intrathoracic esophagogastric anastomosis
Good mediastinal lymphadenectomy
Common for middle/lower thoracic esophageal and GEJ tumors

Three-Incision Esophagectomy: McKeown

Abdominal + right thoracic + cervical incisions
Cervical anastomosis
Useful for higher tumors where proximal margin is important
Allows extensive lymphadenectomy

Other Techniques

Minimally invasive esophagectomy or hybrid esophagectomy can reduce surgical trauma in experienced centers
Colon or jejunal interposition rarely used when stomach is unavailable
Cervical esophageal tumors are often treated with definitive chemoradiotherapy to avoid mutilating surgery

4. Definitive Chemoradiotherapy

Curative-intent treatment without planned surgery
Indications:

Medically inoperable patient
Unresectable localized tumor without distant metastasis
Cervical esophageal cancer
Selected SCC where organ preservation is preferred

Requires close follow-up for persistent/recurrent local disease
Salvage esophagectomy may be considered in selected fit patients, but morbidity is high

5. Metastatic / Irresectable Tumors: Palliative Therapy

Goals: relieve dysphagia, maintain nutrition, control symptoms, prolong survival if possible
Dysphagia palliation:

Self-expanding metal stent (SEMS)
Endoscopic dilatation for selected strictures; perforation risk
Palliative radiotherapy or chemoradiotherapy
Endoscopic tumor ablation in selected cases

Nutritional support:

Dietitian review, high-calorie supplements
Enteral feeding if oral intake is inadequate
Jejunostomy often preferred when curative esophagectomy is planned or stomach must be preserved as conduit
Gastrostomy/PEG can be used in selected palliative patients, but planning must consider future surgery and tumor location

Systemic therapy:

Chemotherapy for metastatic disease
Immunotherapy / chemoimmunotherapy depending on histology, PD-L1 and local protocol
HER2-targeted therapy for HER2-positive metastatic adenocarcinoma when indicated

Complication palliation:

Tracheo-esophageal fistula → covered stent, airway evaluation, infection control
Bleeding → endoscopic/radiological/radiotherapy measures depending on severity
Pain → analgesia, palliative care involvement

Complications of Treatment

After esophagectomy:

Anastomotic leak
Pulmonary complications: pneumonia, atelectasis, respiratory failure
Recurrent laryngeal nerve injury, especially cervical/high dissection
Chylothorax from thoracic duct injury
Conduit ischemia/necrosis
Anastomotic stricture
Delayed gastric emptying, reflux, dumping, weight loss

After chemoradiotherapy:

Esophagitis, dysphagia, malnutrition
Myelosuppression
Radiation pneumonitis
Stricture or fistula in advanced tumors