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Cosnes et al demonstrated that previous appendicectomy is not only associated with a lower incidence of ulcerative colitis, but also with a less severe course of the disease. Although we can fully agree with this result, we disagree with the recommendation that “Patients genetically at high risk of developing ulcerative colitis may be considered as candidates for appendicectomy with the objectives of preventing the development of ulcerative colitis and also decreasing its severity” (Gut 2002;51:803–7).
All previous studies, as well as the present study, have demonstrated an association only between previous appendicectomy and ulcerative colitis. It has not been shown that performing appendicectomy in healthy persons at increased risk of developing ulcerative colitis is beneficial. The association may as well have been caused by an unknown confounding factor, both leading to an increased risk of appendicitis and a decreased risk of developing (severe) ulcerative colitis. To illustrate this point is the following theoretical example: an epidemiological study on cardiovascular morbidity finds that the risk of cardiovascular events is inversely related to the risk of developing upper gastrointestinal haemorrhage. This could be due to the factor “treatment with aspirin” that could well explain the increased bleeding risk and the lower incidence of cardiovascular events. The confounding factor is the use of aspirin. It would be wrong to conclude that in patients without a history of bleeding, attempts should be undertaken to induce upper gastrointestinal bleeding in order to prevent cardiovascular morbidity.
Another argument against performing this surgical procedure in healthy persons is the finding that appendicectomy in the absence of an inflamed appendix was not associated with a decreased risk of ulcerative colitis, suggesting that appendicitis rather than appendicectomy protects against ulcerative colitis.1 Cosnes et al state that these results may not be correct as they included all patients with previous appendicectomy and still found a less severe course. We believe they are incorrectly assuming this, as another possible explanation is that the effect of appendicitis is actually higher than the effect of appendicectomy reported in the present study, which could have been diluted by inclusion of patients without appendicitis.
In conclusion, we believe that at present healthy persons at risk of developing ulcerative colitis should not be considered candidates for appendicectomy outside clinical trials as evidence showing that appendicectomy will protect these persons is lacking.
Many French surgeons in 1900 did recommend removing preventively all appendixes of young people (see Marcel Proust, “A l’ombre des jeunes filles en fleur”). That was not our purpose. Indeed, the sentence pointed out by ter Borg and van Buuren in our paper did not give a recommendation but only made a suggestion to consider for appendicectomy patients genetically at high risk of developing ulcerative colitis.
Ter Borg and van Buuren speculate that appendicectomy and a benign course of ulcerative colitis may be linked through a confounding factor but they do not document their hypothesis. In fact, there is a large body of evidence supporting a causal relationship between appendicectomy and no (or benign) ulcerative colitis, and the strongest demonstration of this relationship is the protective effect of early appendicectomy in the T cell receptor α (TCR-α) knockout mouse model.1 Note also that the Swedish study2 which found that only appendicectomy for inflammatory conditions protects against ulcerative colitis did not take into account cases of mild ulcerative colitis, a subgroup in which appendicectomised patients may be over represented.
Finally, we do not believe that the effect of appendicectomy on the course of ulcerative colitis is so high that it would remain after excluding all patients without appendicitis, thus probably two thirds of our patients.3 A key point however, like in the TCR-α knockout mouse model, is the date of appendicectomy. Appendicectomy protects against severe ulcerative colitis only when performed at a young age,2 and before disease onset.4,5 This latter observation argues against any therapeutic effect of appendicectomy after onset of ulcerative colitis. The problem is different when considering patients at risk for the disease.
We do believe that in a few years it will be possible to screen out young patients with a predisposing genotype for ulcerative colitis, and a clinical trial assessing the benefits of prophylactic appendicectomy will be warranted.