The pouchitis, we look at histology, clinical factors, diarrhea, cramping, perhaps blood in the stool. We look at endoscopic findings. And we put these together and then we say a patient has pouchitis. However, is there anything in the history-serologically or otherwise-that will tell us who is at the higher risk to develop pouchitis. And several things have been looked at, trying to address this directly.

Number one, the anti-Saccharomyces cerevisiae antibody or ASCA. If there is a double positive, this suggests that the individual has a high propensity to have Crohn's disease. So, yes, that individual will likely have pouchitis, but it's Crohn's pouchitis, not necessarily ulcerative colitis-related pouchitis. So this might be an individual you would think twice about doing a pouch and perhaps do further investigations to better differentiate.

The other serology that's been looked at directly is the ANCA, the anti-neutrophil cytoplasmic antibody. This differs from the ANCA we look at in Wegener's granulomatosis; it's the p-ANCA. And the presence of a high titer p-ANCA that's positive before surgery has been looked at. And it's been suggested that those individuals may have a high rate of pouchitis post-operatively.

But the question comes up: So what? Will you not do the surgery on that particular patient, based on the presence of a high p-ANCA? And most of us would say, no, we would do the surgery. However, we should beware that they may develop pouchitis. And it may be in the treatment of individuals with certain medications-whether they be probiotics, such as VSL-3, which has been looked at, or other probiotics or specific medications that will prevent that individual from developing pouchitis in the future. This particular trial has not been done.

We've had a trial that has looked at individuals-in fact, two trials that have looked at individuals that have had pouchitis. And those individuals were given antibiotics followed by VSL-3. And over the course of one year, the rate of pouchitis was substantially decreased compared to that of placebo. So this might be a way to look directly and to see: Can we alter the clinical course of these particular patients, improve their quality of life, allow them to work and not miss days from work?

But there are other things as well that have to be considered. It's not only serologies. When we look at an individual with ulcerative colitis, we look at the immune system in general. Is it "revved up?" Do individuals have extraintestinal manifestations of inflammatory bowel disease? Erythema nodosum, pyoderma gangrenosum; these will portend a higher likelihood of developing pouchitis.

Is the individual a smoker? Smoking itself has been helpful in ulcerative colitis. However, those that smoke that have had ulcerative colitis may develop pouchitis. And when I say "helpful," it means that those individuals that stop smoking that might go back and restart smoking, while having active symptoms of ulcerative colitis, may go into remission. Now I certainly don't advocate smoking, given the other potential side effects that may come about, such as cerebrovascular disease, cardiovascular disease, etc. But given this, this is a suggestion that you might have a premonitory symptom or sign or laboratory parameter that will predict.

It would be nice to take all of these factors and look at patients prospectively to see can we predict, and to a decision analysis in the future. Is it worthwhile to give these individuals the opportunity to have surgery, that have extraintestinal manifestations, that have the ANCA that's highly positive. And once again, we need to do this particular evaluation. But at this point in time, we all offer surgery but look for the potential for pouchitis.

So it is something that is relatively common. I should mention, as well, approximately 50% of individuals-based on a prospective evaluation of patients that had had ileo-anal J-pouch surgery at the Mayo Clinic-15 years out developed pouchitis.

It's not those that develop pouchitis that we're concerned about; it's more those that develop chronic refractory pouchitis. And this represents a minority of individuals. It's important to define who they are, what the predictors are and, most importantly, can we alter that directly? And pyoderma gangrenosum, can we alter that? Well, we know certain medications do work to treat that, but prophylactic treatment post-surgery has not been done. And that's arguably where we should focus our attention in these particular patients.

So it's an area of extreme interest. It's an area of concern to patients and physicians alike that deserves better study.