What do you do if you find a Barrett’s? What I like to do is to look very carefully for any suspicious nodularity or stricture at endoscopy and to first biopsy any nodule or stricture. Benign ulcers usually are benign. Then, sample the whole of the Barrett’s esophagus by taking four-quadrant biopsies, as shown with these little x’s, all the way down the Barrett’s esophagus to try to find anything that might be hidden there.

What are we looking for? Well, besides cancer, we are looking for dysplasia, which is a precancerous condition. This is taken from a resection specimen, to get a nicer picture, but this is a Barrett’s, and if you look at this side of this villous-like structure, you will see the obvious goblet cells here. Here, the nuclei are at the base of the cells in order and that is non-dysplastic here. Now, when we look at the other side of this villous structure here, there are more nuclei. The nuclei are above other nuclei; that is, they are stratified. This is low-grade dysplasia; that is non-dysplastic Barrett’s, low-grade dysplasia. The same is true here; this is non-dysplastic here and this is low-grade again. There are too many nuclei here and the nuclei are stratified. This is common and we have found low-grade dysplasia in about a third of our patients and high-grade dysplasia in considerably less than 5%. Here is high-grade dysplasia. On this side you will see lots of nuclei; large, densely-staining nuclei, not much cytoplasm and the nuclei extend up to the lumen surface of the cells. On this side, it is even worse; there is very high-grade dysplasia with malignant-looking cells. These really are cancer cells to look at, but my pathologist colleague tells me that because they actually haven’t broken through the basal lamina, which is there and here, this is by definition high-grade dysplasia and not invasive adenocarcinoma; it is sometimes difficult to tell the difference on a biopsy.

If you were to operate on someone with high-grade dysplasia in different series, anywhere from about 10 to 50% of patients in whom the endoscopist has found Barrett’s high-grade dysplasia and not seen a cancer, cancer is found in 10% to 50% in the resected specimen, depending on how carefully it has been looked for. Some of these patients have a cancer right now; others will get a cancer later.

The same patient, approximately one year later, had another endoscopy and he had developed a Barrett’s esophagus in the meantime. Here on the right is the typical epithelium found in a Barrett’s esophagus – glandular; note the goblet cells. You can see the little sort of oval holes in the cells here. This is intestinal metaplasia; this is not the normal type of epithelium found at the upper end of the stomach . This is the hallmark of Barrett’s esophagus and the type of epithelium that most adenocarcinomas of the esophagus are found to occur in.

Here are some endoscopic pictures; we are looking down in about the mid esophagus here at an untreated patient with Barrett’s esophagus. You will see these erosions, these triangular, pale-centered, bright-red margined lesions in the squamous mucosa. This is typical reflux esophagitis. If you look further down here, however, you will see red mucosa which covers a long segment of the lower esophagus and that is the Barrett’s mucosa. Here, on the retroflexed view, looking upward, is the hiatal hernia that this patient had.

Supposing we treat a patient like this effectively to prevent reflux, either with proton pump inhibitors, such as omeprazole, or with a laparoscopic Nissen. What will happen? What will probably happen is that you will control their heartburn and acid reflux and their esophagitis will resolve if you endoscope them again, but the Barrett’s is almost certain to remain. It may develop squamous islands. These are squamous islands partially occupying some of the area of columnar mucosa. Doing an anti-reflux operation, or controlling with Prilosec, has not been shown to reduce the cancer risk in the remaining Barrett’s esophagus, so you still have to keep on with surveillance.
Breast cancer
What is the risk of adenocarcinoma in patients with Barrett’s? There are many series; these are just three of the larger, more recent series, number of patients followed, number of follow up years median and the number of cancers per patient years. Take the top series of 166 patients, followed for an average of 9.3 years, one cancer per 180 follow up years, or out of 180 patients, one would get cancer each year. That looks bad, but it isn’t quite as bad as you might think. Some patients we see with Barrett’s really feel sure that they are going to die of cancer, but that is just not the case.

Here are four series, one of which was a paper I had in the New England Journal in 1985; these are longer follow ups. These are patients followed up 3-cm Barrett’s or longer, the number of follow up years and if you follow people for long enough, a proportion will die of a cause of some sort. If you follow everyone in this room for 100 years, you would get 100% mortality. So if you follow people with Barrett’s long enough, people will die of something. These are the numbers of those who died and these are the numbers of those who died of cancer of the esophagus; it was between 2.5 and 6%, roughly about 5%. Therefore, in these series, with the present methods of management, only about 5% of patients with a long-segment Barrett’s actually died of esophageal cancer. We sometimes find early cancers in these people, and at least four other patients in these different series developed a cancer but did not die of the cancer, they died of something else. That is quite different from a cancer causing an obstructive mass in the esophagus. So, 95% of patients with Barrett’s will not die of esophageal cancer.