Wednesday, October 7, 2009

Does Reflux Matter?

Most cases of esophageal adenocarcinoma start with Barrett's esophagus and most cases of Barrett's esophagus start with reflux. Does it follow that stopping reflux can halt the cancerous progression of Barrett's esophagus? I'm not so sure.

As you would expect, reflux isn't made up of just acid. It includes partially digested food, bacteria, stomach acid, and bile, among other constituents. And, it seems that both acid and bile reflux play important roles in the development of Barrett's esophagus.

It is not as clear that reflux causes Barrett's esophagus to progress to cancer as it is that reflux causes Barrett's esophagus to develop in the first place. For example, surgical correction of the lower esophageal sphincter doesn't seem to be better than acid suppression at reducing the risk cancer in people with Barrett's esophagus. Likewise, consumption of substances, like alcohol, that increase reflux don't seem to be significantly associated with the progression of Barrett's esophagus to cancer. On the other hand, excessive consumption of alcohol in early-life (presumably before the development of Barrett's esophagus) is strongly associated with having Barrett's esophagus later in life.

One manner in which reflux may contribute to the cancerous progression of Barrett's esophagus is by causing damage to the esophagus that results in chronic inflammation. Acid suppression seems to reduce this chronic inflammation, which is why I take a PPI every day. There are different viewpoints on whether acid suppression is cost-effective chemoprevention for esophageal adenocarcinoma - for example, see this. Having studied both sides of the debate, I suspect it's wise to suppress acid at least enough to control chronic inflammation. Unfortunately, there have been no placebo controlled trials on the efficacy of PPIs for chemoprevention of esophageal adenocarcinoma, so we don't know for sure and are unlikely to know for some time.

Beyond contributing to chronic inflammation, I suspect that reflux plays a relatively minor role in the progression of Barrett's esophagus to cancer. Instead, my guess is that once a person gets Barrett's esophagus, the Barrett's cells that have formed are on march towards cancer that is principally modulated by (i) inflammation, (ii) diminished genetic stability/cellular adhesion, and (iii) poor immune response.

That said, I still worry about reflux for three reasons:

1. Since I only have short segment Barrett's esophagus (about 1 cm), there are still many more cells in the vicinity of my dysfunctional LES that could "go rogue" (i.e., become Barrett's esophagus cells). Since the the chance of progressing to cancer seems to depend, to some extent, of the amount of Barrett's cells one has, I would like to have fewer Barrett's cells if possible.

2. Acid suppression doesn't do much to prevent bile reflux, and bile reflux may contribute to inflammation.

3. There's a chance that reflux is a player (beyond its effect on inflammation) in the progression of esophageal cancer after all.

1 comment:

  1. Solid, evidence-based, and balanced (like the site in general).