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Cancers of the upper gastrointestinal tract include malignancies of the esophagus, stomach, and small bowel. Esophageal, gastroesophageal junction, and gastric cancers are among the most common of human malignancies, with 1.5 million global new cases diagnosed in 2018. In the United States, a lower risk area, it is estimated that in 2020, esophageal cancer will be diagnosed in 18,440 people and cause 16,170 deaths; for gastric cancer, 27,600 new cases will be diagnosed and 11,010 deaths will occur. Small intestine cancers are rare.



Two distinct forms of cancer with different epidemiologies, causative factors, and genomic profiles arise within the esophagus: squamous cell cancers, which occur more frequent in the upper and mid esophagus; and adenocarcinomas, which are almost always located in the lower esophagus and at the gastroesophageal junction. The incidence of esophageal cancer varies up to 20-fold based on geographic distribution: it is relatively uncommon in North America, but has a high incidence in Asia (especially China), the Normandy coast of France, and Middle Eastern countries such as Iran. This marked global variation is likely due to different causative factors in the development of the malignancy, leading to two different cancer types within the same tissue: squamous cell cancers are more common in high-incidence areas, usually with lower Human Development Index (HDI) scores (a measure of economic development that includes standard of living, health, and education). Overall, approximately 572,000 new cases of esophageal cancer were diagnosed globally in 2018; esophageal cancer was the seventh most common cause of malignancy and the third most common cause of cancer-related mortality, with an estimated 508,000 deaths.

The clearest high-risk factors for the squamous cell cancer subtype in Western countries are alcohol and tobacco abuse; concurrent alcohol and tobacco abuse further increases the risk. Ingestion of extremely hot substances (such as tea in Iran and mate [maté] in South America) has been proposed as a risk factor; in India, chewing the areca (betel) nut increases the risk of esophageal squamous cell cancers. Less common risk factors include chronic achalasia, radiation therapy (such as is delivered for treatment of Hodgkin’s lymphoma or breast cancer), lye ingestion, and Plummer-Vinson (Patterson-Kelly) syndrome (iron deficiency anemia, glossitis, cheilosis, and the development of esophageal webs) (Table 80-1). Adenocarcinoma of the lower esophagus and gastroesophageal junction has been the predominant histologic subtype in the United States and Western Europe for several decades, now making up >75% of all incident cases. Risk factors for adenocarcinoma (Table 80-2) include chronic reflux esophagitis leading to inflammation and the development of Barrett’s esophagus (the finding of glandular gastric type mucosa extending into the esophagus). Although obesity increases the risk of reflux esophagitis, a substantial number of patients with newly diagnosed adenocarcinoma of the esophagus and gastroesophageal junction are younger and fit; Barrett’s esophagus may still be found in these patients. In ...

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