Chapter 087. Gastrointestinal Tract Cancer (Part 1) Harrison's Internal Medicine > Chapter 87. Gastrointestinal Tract Cancer Gastrointestinal Tract Cancer: Introduction The gastrointestinal tract is the second most common noncutaneous site for cancer and the second major cause of cancer-related mortality in the United States. Esophageal Cancer Incidence and Etiology Cancer of the esophagus is a relatively uncommon but extremely lethal malignancy. The diagnosis was made in 15,560 Americans in 2007 and led to 13,940 deaths. Worldwide, the incidence of esophageal cancer varies strikingly. It occurs frequently within a geographic region extending from the southern shore of the Caspian Sea on the west to northern China on the east and encompassing parts of Iran, Central Asia, Afghanistan, Siberia, and Mongolia. High-incidence "pockets" of the disease are also present in such disparate locations as Finland, Iceland, Curaçao, southeastern Africa, and northwestern France. In North America and western Europe, the disease is more common in blacks than whites and in males than females; it appears most often after age 50 and seems to be associated with a lower socioeconomic status. A variety of causative factors have been implicated in the development of the disease (Table 87-1). In the United States, esophageal cancer cases are either squamous cell carcinomas or adenocarcinomas. The etiology of squamous cell esophageal cancer is related to excess alcohol consumption and/or cigarette smoking. The relative risk increases with the amount of tobacco smoked or alcohol consumed, with these factors acting synergistically. The consumption of whiskey is linked to a higher incidence than the consumption of wine or beer. Squamous cell esophageal carcinoma has also been associated with the ingestion of nitrites, smoked opiates, and fungal toxins in pickled vegetables, as well as mucosal damage caused by such physical insults as long-term exposure to extremely hot tea, the ingestion of lye, radiation-induced strictures, and chronic achalasia. The presence of an esophageal web in association with glossitis and iron deficiency (i.e., Plummer-Vinson or Paterson-Kelly syndrome) and congenital hyperkeratosis and pitting of the palms and soles (i.e., tylosis palmaris et plantaris) have each been linked with squamous cell esophageal cancer, as have dietary deficiencies of molybdenum, zinc, and vitamin A. Table 87- 1 Some Etiologic Factors Believed to Be Associated with Esophageal Cancer Excess alcohol consumption Cigarette smoking Other ingested carcinogens Nitrates (converted to nitrites) Smoked opiates Fungal toxins in pickled vegetables Mucosal damage from physical agents Hot tea Lye ingestion Radiation-induced strictures Chronic achalasia Host susceptibility Esophageal web with glossitis and iron deficiency (i.e., Plummer- Vinson or Paterson-Kelly syndrome) Congenital hyperkeratosis and pitting of the palms and soles (i.e., tylosis palmaris et plantaris) ? Dietary deficiencies molybdenum, zinc, vitamin A ? Celiac sprue Chronic gastric reflux (i.e., Barrett's esophagus) for adenocarcinoma For unclear reasons, the incidence of squamous cell esophageal cancer has decreased somewhat in both the black and white population in the United States over the past 30 years, while the rate of adenocarcinoma has risen dramatically, particularly in white males. Adenocarcinomas arise in the distal esophagus in the presence of chronic gastric reflux and gastric metaplasia of the epithelium (Barrett's esophagus), which is more common in obese persons. Adenocarcinomas arise within dysplastic columnar epithelium in the distal esophagus. Even before frank neoplasia is detectable, aneuploidy and p53 mutations are found in the dysplastic epithelium. These adenocarcinomas behave clinically like gastric adenocarcinoma and now account for >60% of esophageal cancers. . Chapter 087. Gastrointestinal Tract Cancer (Part 1) Harrison's Internal Medicine > Chapter 87. Gastrointestinal Tract Cancer Gastrointestinal Tract Cancer: Introduction The gastrointestinal. gastrointestinal tract is the second most common noncutaneous site for cancer and the second major cause of cancer- related mortality in the United States. Esophageal Cancer Incidence and Etiology Cancer. the disease (Table 87 -1). In the United States, esophageal cancer cases are either squamous cell carcinomas or adenocarcinomas. The etiology of squamous cell esophageal cancer is related to