A 57-year-old obese man visits his doctor with a complaint of troubling heartburn. He does not report pain or difficulty with swallowing, but he does wake up in the night with searing chest pain typically several times per week. He has been avoiding spicy foods, and taking ranitidine (tradename: Zantac), a nonprescription histamine antagonist (specific for histamine H2 receptors).
In the stomach, what cell releases histamine, and what cell responds to it (i.e. has histamine receptors)?
Due to the patient’s age and the fact that he is obese, the doctor decides to refer him for examination of the esophagus by endoscopy. In the endoscopic examination, the surface of the upper esophagus is pale and glossy (the normal appearance), but the distal 5 cm is a darker pink color. The distal region also has scattered small erosions (areas of tissue damage).
What is the normal type of epithelium found in the esophagus, which gives the pale and glossy appearance in endoscopy?
Gastroesophageal reflux disease (GERD) is treated with drugs that reduce acid secretion. For erosive esophagitis, as this patient has, the usual treatment approach is to use “step down” therapy, in which a higher dose of drug is used initially, and then reduced to a lower dose once symptoms resolve.
The doctor prescribes omeprazole, to be taken at a dose of 80 mg daily.
What protein, found in parietal cells, is the target of omeprazole?
A biopsy from the distal esophagus in the pinkish region shows that this patient has Barrett’s esophagus. In Barrett’s esophagus, there is a characteristic transformation of the mucosa, which is called intestinal metaplasia.
What type of epithelium is seen with intestinal metaplasia? In particular, what mucus-secreting cell would be seen in this biopsy?
Intestinal metaplasia is considered a premalignant change, since Barrett’s esophagus greatly increases the risk for esophageal adenocarcinoma. Esophageal adenocarcinoma is a rare but devastating form of cancer. Individuals with Barrett’s esophagus have about a 30-fold increase in the risk of developing esophageal adenocarcinoma compared to the general public; however the absolute risk of developing cancer is still quite low. A recent large study in Denmark found that the risk of progression to esophageal adenocarcinoma was roughly 1 in 1000 for individuals with Barrett’s esophagus and no other tissue changes. The risk is higher if the biopsy shows dysplasia, in which there are cellular abnormalities that indicate the beginnings of malignant transformation leading to cancer.
There is controversy about the appropriate management of Barrett’s esophagus. The general thinking is that it should be monitored with endoscopic surveillance, so that dysplasia can be identified and treated before it progresses to adenocarcinoma. Nevertheless, it has been difficult to show that increased surveillance provides a survival benefit.
In this patient, after the initial treatment with high dose omeprazole, his symptoms improved. A follow-up endoscopy showed that the erosions had healed, although the area of intestinal metaplasia remained similar in size. The patient continued on a lower dose of omeprazole and agreed to start a weight loss program. Because the biopsy showed no dysplasia, it was recommended that he plan on another endoscopy in 3 to 5 years.
If you are interested in seeing the appearance of Barrett's esophagus during endoscopy, check out figure 1 in this paper:
Sharma, P. (2009) Barrett's Esophagus. New England Journal of Medicine 361: 2548-2556 (link)
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