Esophageal Cancer for the ABIM Exam
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Esophageal Cancer for American Board of Internal Medicine Exam
Definition
- Esophageal Cancer: A malignancy arising from the esophagus, categorized into two main histological types:
- Squamous cell carcinoma (SCC): Most common worldwide, originating from the squamous epithelium of the esophagus.
- Adenocarcinoma: Predominantly found in Western countries, arising from the metaplastic columnar epithelium in Barrett’s esophagus.
Epidemiology
- Squamous Cell Carcinoma:
- Predominates globally, particularly in regions like Asia, Africa, and parts of Europe.
- Typically occurs in the mid to upper esophagus.
- Adenocarcinoma:
- More common in the U.S. and Western countries.
- Strongly associated with GERD and Barrett’s esophagus, typically arising in the distal esophagus.
- Risk Factors:
- Squamous Cell Carcinoma: Smoking, alcohol use, achalasia, hot beverages, prior esophageal injury (e.g., lye ingestion).
- Adenocarcinoma: Chronic GERD, Barrett’s esophagus, obesity, smoking, and a diet low in fruits and vegetables.
Pathophysiology
- Squamous Cell Carcinoma:
- Develops from the squamous cells lining the esophagus in response to chronic irritation (e.g., from tobacco or alcohol).
- Tumors most commonly occur in the middle third of the esophagus.
- Adenocarcinoma:
- Arises from dysplastic changes in Barrett’s esophagus, which is caused by chronic GERD. Long-term acid exposure leads to metaplasia, where the normal squamous epithelium transforms into columnar epithelium, progressing to dysplasia and adenocarcinoma.
- Typically found in the distal esophagus near the gastroesophageal junction.
Clinical Features
- Dysphagia: The most common presenting symptom, initially to solid foods and later to liquids as the tumor narrows the esophageal lumen.
- Odynophagia: Painful swallowing, particularly with advanced disease.
- Weight Loss: Significant unintentional weight loss is common, often due to decreased oral intake and cancer-related cachexia.
- Chest Pain: Retrosternal discomfort or pain may occur, especially with advanced disease.
- Hoarseness: A sign of recurrent laryngeal nerve involvement, indicating locally advanced disease.
- Hiccups: May result from tumor invasion of the diaphragm or phrenic nerve involvement.
- GI Bleeding: Occult or overt bleeding can occur due to tumor ulceration.
- Aspiration Pneumonia: Secondary to esophageal obstruction or tracheoesophageal fistula formation.
Diagnosis
- Endoscopy with Biopsy:
- Esophagogastroduodenoscopy (EGD): The gold standard for diagnosing esophageal cancer. Allows direct visualization of the tumor and biopsy for histologic confirmation.
- Biopsy is essential to differentiate between squamous cell carcinoma and adenocarcinoma.
- Barium Swallow:
- May show a “stricture” or “apple core lesion” in the esophagus, suggestive of an obstructing tumor. Used for initial evaluation of dysphagia.
- Endoscopic Ultrasound (EUS):
- Provides detailed information about the depth of tumor invasion (T stage) and assesses regional lymph node involvement (N stage). Helps in staging and treatment planning.
- CT Scan:
- CT of the chest and abdomen is performed to evaluate for local invasion and distant metastasis, commonly to the liver, lungs, and adrenal glands.
- Positron Emission Tomography (PET):
- Used to detect metastatic disease and to determine the extent of distant spread. PET/CT is frequently used in conjunction with CT for staging purposes.
- Bronchoscopy:
- May be performed if there is concern for airway involvement or tracheoesophageal fistula in patients with proximal esophageal tumors.
Staging
- TNM Staging:
- T (Tumor): Assesses depth of invasion of the tumor into the esophageal wall and surrounding structures.
- Tis: Carcinoma in situ (high-grade dysplasia).
- T1: Invasion into the lamina propria or submucosa.
- T2: Invasion into the muscularis propria.
- T3: Invasion through the adventitia.
- T4: Invasion into adjacent structures (e.g., aorta, trachea).
- N (Nodes): Regional lymph node involvement.
- N0: No regional lymph node metastasis.
- N1-N3: Increasing numbers of involved lymph nodes.
- M (Metastasis): Distant metastasis.
- M0: No distant metastasis.
- M1: Distant metastasis present.
- Prognosis:
- Prognosis depends on the stage at diagnosis. Early-stage disease (T1 or T2) has a significantly better prognosis compared to locally advanced (T3 or T4) or metastatic disease (M1).
- Five-year survival rates range from 40-50% for localized disease to less than 10% for metastatic disease.
Treatment
- Surgical Resection:
- Esophagectomy: The primary curative treatment for localized or locally advanced esophageal cancer without distant metastasis. The type of esophagectomy (transthoracic vs. transhiatal) depends on tumor location and extent.
- Minimally invasive esophagectomy: May be an option in select patients.
- Endoscopic Resection:
- For very early-stage disease (Tis or T1a), endoscopic mucosal resection (EMR) can be curative.
- Endoscopic submucosal dissection (ESD) is another technique used for superficial tumors.
- Neoadjuvant Chemoradiotherapy:
- For locally advanced disease (T2 or higher), neoadjuvant chemoradiation (preoperative) is standard. Chemotherapy (cisplatin and 5-fluorouracil) combined with radiation therapy has been shown to increase resectability and improve survival rates.
- Definitive Chemoradiotherapy:
- For patients who are not surgical candidates or refuse surgery, definitive chemoradiotherapy can be curative, particularly in squamous cell carcinoma.
- Palliative chemoradiotherapy may be used for symptom control in metastatic disease.
- Targeted Therapy:
- For advanced adenocarcinoma, HER2-positive tumors may be treated with trastuzumab in combination with chemotherapy.
- Immunotherapy:
- PD-1 inhibitors (e.g., pembrolizumab) have shown benefit in patients with advanced or metastatic esophageal cancer, especially those with high PD-L1 expression.
- Palliative Care:
- For advanced-stage disease, palliation is focused on relieving symptoms such as dysphagia and pain.
- Esophageal stenting: Used to relieve obstructive symptoms in unresectable or metastatic disease.
- Palliative radiation therapy: Helps alleviate dysphagia and pain.
- Nutritional support: May involve enteral feeding (e.g., percutaneous endoscopic gastrostomy) or total parenteral nutrition in advanced disease.
Prevention
- Tobacco and Alcohol Cessation: Reducing the risk of squamous cell carcinoma by eliminating known carcinogens.
- Management of GERD and Barrett’s Esophagus: Chronic GERD management with PPIs and surveillance endoscopy in patients with Barrett’s esophagus can reduce the risk of progression to adenocarcinoma.
- Dietary Modifications: A diet rich in fruits, vegetables, and fiber may reduce the risk of both SCC and adenocarcinoma.
Complications
- Tracheoesophageal Fistula: Occurs due to tumor erosion into the trachea, causing aspiration and recurrent pneumonia.
- Esophageal Perforation: Can occur spontaneously or during interventions like endoscopy.
- Metastasis: Common sites include the liver, lungs, and bones.
Key Points
- Esophageal cancer is classified as either squamous cell carcinoma (most common worldwide) or adenocarcinoma (common in Western countries, associated with GERD and Barrett’s esophagus).
- Major risk factors for SCC include smoking, alcohol, and hot beverages, while adenocarcinoma is associated with GERD, Barrett’s esophagus, and obesity.
- Symptoms include dysphagia, weight loss, odynophagia, and chest pain. Diagnosis is confirmed with endoscopy and biopsy.
- Treatment for localized disease includes esophagectomy, while chemoradiation is used for locally advanced disease. Advanced disease may be treated with palliative care and targeted therapies.
- Early detection in Barrett’s esophagus and appropriate management of GERD are key to preventing adenocarcinoma.