Esophageal cancer, or carcinoma of the esophagus, is a malignant tumor originating from the epithelial lining of the esophageal mucosa, primarily presenting as squamous cell carcinoma or adenocarcinoma. The typical symptom during the advanced stages is progressive dysphagia. Esophageal cancer is a common malignancy worldwide. Its epidemiological characteristics include the following:
- Higher Incidence in Rural Populations: The incidence rate in rural areas is higher than in urban areas.
- Gender Difference: The incidence rate is higher in males than in females.
- Age Susceptibility: Middle-aged and elderly individuals are more prone to the disease.
Pathogenesis
The development of esophageal cancer is primarily associated with the following factors:
Nitrosamines and Mycotoxins
In high-incidence areas, the levels of nitrosamines in food and drinking water are significantly higher than in other regions, showing a positive correlation with the prevalence of esophageal cancer.
Fungi such as Aspergillus flavus and Fusarium in moldy food can reduce nitrates to nitrites, promoting the synthesis of carcinogenic substances like nitrosamines. These often act synergistically with nitrosamines in causing cancer.
Chronic Physical and Chemical Irritation and Inflammation
Chronic irritation of the esophageal mucosa caused by consuming coarse or overly hot food, long-term alcohol consumption, and smoking increases the risk of esophageal cancer. Additionally, chronic esophageal conditions such as gastroesophageal reflux disease, corrosive esophageal injury and strictures, achalasia, and esophageal diverticula contribute to an increased incidence of esophageal cancer.
Nutritional Factors
Deficiencies in vitamins (A, B2, C, E, folic acid) and trace elements such as zinc, selenium, and molybdenum are risk factors for esophageal cancer.
Genetic Factors
Esophageal cancer often shows familial clustering, with 25%–50% of cases in high-incidence areas having a positive family history. Furthermore, under the combined influence of genetic and environmental factors, the inactivation of tumor suppressor genes (e.g., RB1, TP53, CDKN2A), activation of oncogenes (e.g., HRAS, MYC, DCPS), and changes in the expression of cell cycle regulatory genes (e.g., CCND1) are all associated with the development of esophageal cancer.
Pathological Anatomy and Pathophysiology
The majority of esophageal cancer lesions are located in the middle segment of the esophagus, followed by the lower segment, with the upper segment being the least common. When gastric cardia cancer extends into the lower esophagus, it is clinically difficult to distinguish from lower esophageal cancer and is referred to as esophagogastric junction cancer.
Gross Pathology
Early Esophageal Cancer
Lesions are confined to the mucosal layer and superficial submucosal layer and are not accompanied by lymph node metastasis. Endoscopic findings include congestion, plaques, erosion, and papillary changes.
Congested (occult) type is often carcinoma in situ and represents an early manifestation of esophageal cancer.
Plaque type is the most common, with better differentiation of cancer cells.
Erosion type is less common and typically shows poorer differentiation of cancer cells.
Papillary type is primarily early invasive cancer, with generally well-differentiated cancer cells.
Advanced Esophageal Cancer
The cancer tissue progressively involves the entire circumference of the esophagus, protrudes into the lumen, or penetrates the esophageal wall to invade adjacent tissues or organs. Based on morphological characteristics, it can be classified into medullary, fungating, ulcerative, constrictive, and intraluminal types.
Histopathology
Approximately 90% of esophageal cancers are squamous cell carcinomas, with a smaller proportion being adenocarcinomas. Adenocarcinomas are often associated with malignant transformation in Barrett’s esophagus.
Patterns of Spread and Metastasis
Direct Spread
Cancerous tissue initially infiltrates the submucosa and muscularis layers. After penetrating the esophageal wall, it spreads to surrounding tissues and organs.
Lymphatic Metastasis
This is the primary route of metastasis for esophageal cancer.
Hematogenous Metastasis
In advanced stages, metastasis commonly occurs in the liver, lungs, bones, and other organs.
Clinical Manifestations
Early Symptoms
Early symptoms are often nonspecific and may include retrosternal discomfort, a burning sensation, or a stabbing or pulling pain. Patients may experience slow passage of food, food retention, or mild choking sensations. These symptoms can vary in intensity and duration, and in some cases, there may be no symptoms at all.
Symptoms in the Advanced Stage
Progressive Dysphagia
This is the hallmark symptom of advanced esophageal cancer and the primary reason most patients seek medical attention. It typically progresses from difficulty swallowing solid food to an inability to swallow liquids.
Food Regurgitation and Emesis
Due to dilation and retention in the proximal esophagus caused by obstruction, food regurgitation or vomiting may occur. The regurgitated or vomited material often contains mucus and/or undigested food and may be blood-tinged or include necrotic tissue.
Pain on Swallowing
This is caused by esophageal erosion, ulcers, or proximal esophagitis. Pain is often exacerbated by hot or acidic foods and may radiate to the neck, scapula, anterior chest, or back.
Other Symptoms
Tumor compression of the recurrent laryngeal nerve may result in hoarseness or choking cough. Phrenic nerve involvement may lead to hiccups. Tumor necrosis, ulceration, or vascular invasion may cause blood vessel rupture, leading to hematemesis and/or melena. Liver metastasis may result in liver dysfunction, jaundice, or even liver failure. Invasion of the trachea or bronchi can cause esophagotracheal or esophagobronchial fistulas, mediastinal abscesses, pneumonia, or lung abscesses, leading to respiratory distress. Bone metastasis may result in pain. Aortic invasion can lead to fatal hemorrhage. Patients in the late stage often present with cachexia.
Physical Signs
Early physical signs may be absent. In the late stage, patients may exhibit emaciation, anemia, malnutrition, dehydration, or cachexia. After metastasis, enlarged, hard superficial lymph nodes or an enlarged liver with nodules may be palpable. A small number of patients may develop ascites or pleural effusion.
Auxiliary Examinations
Endoscopy
Endoscopy is the preferred diagnostic method for esophageal cancer. It allows for direct observation of the lesion morphology and confirmation through histopathological biopsy. Techniques such as chromoendoscopy, electronic chromoendoscopy (e.g., narrow-band imaging), magnifying endoscopy, and confocal laser endomicroscopy (CLE) can improve the detection rate of early esophageal cancer.
Barium Esophagography
This method is an alternative for patients who are not suitable for endoscopy. The main findings on barium esophagography include:
- Destruction of mucosal folds, replaced by irregular and disorganized patterns.
- Localized narrowing of the esophageal lumen, with rigidity at the lesion site and proximal esophageal dilation.
- Irregular filling defects or niches.
CT Scans
CT imaging clearly depicts the anatomical relationship between the esophagus and adjacent tissues and organs, the extent of tumor invasion, and metastatic lesions. It is useful for planning surgical approaches and radiotherapy strategies but is less effective in detecting early-stage esophageal cancer.
Endoscopic Ultrasound (EUS)
EUS is valuable for assessing the depth of esophageal wall invasion, the extent of tumor involvement in surrounding organs, and the presence of abnormal lymph node enlargement. It plays an important role in tumor staging, treatment planning, and prognostic evaluation.
Other Examinations
PET-CT can detect lesions and help identify distant metastases. Currently, there are no specific tumor markers for diagnosing esophageal cancer. Molecular diagnostics or genetic testing may be performed for metastatic esophageal cancer to assist in developing personalized treatment plans.
Diagnosis and Differential Diagnosis
For individuals experiencing slow passage of food, mild choking sensations, or dysphagia, relevant examinations are necessary to confirm the diagnosis.
Esophageal cancer needs to be differentiated from the following conditions:
Achalasia of the Cardia
This condition is caused by dysfunction of the myenteric plexus of the esophageal nerves, leading to impaired relaxation of the lower esophageal sphincter (LES). Clinical manifestations include intermittent dysphagia, food regurgitation, and retrosternal discomfort or pain. The disease typically has a long course and is generally not associated with progressive weight loss. Barium esophagography shows an obstruction at the cardia with a funnel-shaped or bird-beak appearance, smooth edges, and significant dilation of the lower esophagus.
Gastroesophageal Reflux Disease (GERD)
GERD is caused by the reflux of gastric or duodenal contents into the esophagus, resulting in symptoms such as heartburn, chest pain, or dysphagia. Endoscopic examination may reveal mucosal inflammation, erosion, or ulcers, but no tumor cells are found in mucosal biopsies.
Benign Esophageal Stricture
This condition is associated with a history of corrosive or reflux esophagitis, prolonged nasogastric tube placement, or esophageal-related surgeries. Barium esophagography shows esophageal narrowing, loss of mucosal folds, and rigid esophageal walls, without evidence of barium retention defects. Endoscopic examination can confirm the diagnosis.
Globus Hystericus
This condition is more common in women and is characterized by a sensation of a foreign body in the throat, which disappears during eating. It is often triggered by psychological factors and typically lacks organic esophageal abnormalities.
Other Conditions
Dysphagia caused by esophageal leiomyoma, hiatal hernia, esophageal varices, mediastinal tumors, enlarged periesophageal lymph nodes, left atrial enlargement, or aortic aneurysm should also be differentiated from esophageal cancer.
Treatment
The treatment goal for non-metastatic esophageal cancer is to eradicate the lesion, prevent recurrence, and achieve a cure. A comprehensive approach is often employed, including endoscopic treatment, surgery, medication, and radiotherapy. For metastatic esophageal cancer, the treatment goal is to alleviate symptoms and prolong survival, with supportive care and systemic therapy being the main strategies.
Endoscopic Treatment
Early Esophageal Cancer
Endoscopic treatment is an effective option and includes:
- Endoscopic Mucosal Resection (EMR): Removal of the esophageal mucosal lesion in whole or in segments under endoscopy, used for both diagnosis and treatment of superficial esophageal tumors.
- Multi-Band Mucosectomy (MBM): Multiple mucosal resections using a modified esophageal variceal ligator.
- Endoscopic Submucosal Dissection (ESD): Complete dissection of the lesion, including the mucosa and submucosa.
- Non-Resection Endoscopic Treatments: Techniques such as radiofrequency ablation, photodynamic therapy, argon plasma coagulation, and laser therapy.
Advanced Esophageal Cancer
For patients with obstructive symptoms, endoscopic interventions can relieve obstruction, including:
- Simple Dilation: Provides short-term symptom relief but requires repeated dilation and is not suitable for extensive lesions.
- Esophageal Stent Placement: Offers longer-term relief of obstruction to improve quality of life.
- Endoscopic Tumor Ablation: Used for palliative treatment of advanced esophageal cancer.
For patients requiring enteral nutrition, percutaneous endoscopic gastrostomy can improve nutritional status.
Surgical Treatment
Surgery is one of the primary curative approaches for esophageal cancer and is suitable for patients with early-stage or locally advanced disease.
Radiotherapy
Radiotherapy is primarily used for upper esophageal cancer or patients with surgical contraindications. It can also be applied preoperatively or postoperatively.
Chemotherapy
Chemotherapy is commonly used for advanced-stage patients who are not candidates for surgery or radiotherapy. It can also be administered preoperatively or postoperatively. Combination chemotherapy regimens are often preferred to minimize the toxic side effects of high-dose, long-term monotherapy.
Targeted Therapy and Immunotherapy
For metastatic esophageal cancer, individualized treatment can be achieved by targeting specific molecular markers using targeted drugs or immune checkpoint inhibitors.
Prognosis
The prognosis for early-stage esophageal cancer is favorable if timely curative treatment is provided. However, the overall prognosis for advanced-stage esophageal cancer remains poor.
Prevention
Primary Prevention
Measures include improving water quality, preventing food contamination with mold and toxins, and adopting healthier dietary and lifestyle habits.
Secondary Prevention
Early screening in high-risk populations is essential to increase the detection rate of early-stage esophageal cancer.
Tertiary Prevention
Standardized treatment and care aim to improve the prognosis of patients with esophageal cancer.