esophageal adenocarcinoma

Esophageal adenocarcinoma arises from glandular epithelium, typically developing through a metaplasia-dysplasia-carcinoma sequence: chronic GERD causes squamous epithelium of the distal esophagus to undergo intestinal metaplasia (Barrett's esophagus, characterized by goblet cells), which can progress to low-grade dysplasia, high-grade dysplasia, and ultimately adenocarcinoma. Key risk factors include long-standing GERD, obesity (increases intra-abdominal pressure and GERD risk), smoking, and Caucasian ethnicity (contrasts with squamous cell carcinoma, which is more common in Black patients and associated with alcohol/smoking and is typically in the upper/middle esophagus).

Clinical presentation includes progressive dysphagia (solid foods before liquids as the lumen narrows), unintentional weight loss, odynophagia, and possible upper GI bleeding (hematemesis, melena, iron deficiency anemia). Advanced disease may present with hoarseness (recurrent laryngeal nerve involvement), chronic cough (tracheoesophageal fistula), or signs of metastasis (liver, lung, bone).

Diagnosis involves upper endoscopy with biopsy, which is the gold standard. Endoscopic ultrasound (EUS) is used for staging (T and N status), and CT/PET scans assess for distant metastases. Barrett's esophagus surveillance with periodic endoscopy and biopsy is recommended for patients with chronic GERD to detect dysplasia early.

Treatment depends on stage: early-stage/high-grade dysplasia may be treated with endoscopic mucosal resection or radiofrequency ablation. Localized invasive disease often requires esophagectomy, sometimes with neoadjuvant chemoradiation. Advanced/metastatic disease is managed with palliative chemotherapy, targeted therapy (e.g., trastuzumab for HER2-positive tumors), immunotherapy, and stenting for symptom relief.

Prognosis is generally poor due to late presentation, with 5-year survival rates significantly improved when caught at early, localized stages through Barrett's surveillance programs.