The Role of Appendicectomy in Ulcerative Colitis: Systematic Review and Meta-Analysis

To the Editors: We thank Dai and Huang for their interest in our article,1 which demonstrates that prior appendicectomy reduces the risk of future colectomy at the reciprocal increased risk of colorectal cancer and high-grade dysplasia diagnoses. The paucity of data means that the relationship between age at appendicectomy, and its indication, on the pathophysiological course of ulcerative colitis (UC) remains to be elucidated. Certainly, the age-limited expression of protective activation of regulatory T cell FoxP3+CD25+ in response to appendicitis in murine models may contribute to this observation.2-4 While our review identified 7 studies describing the proportion of patients undergoing appendicectomy before 20 years of age, only 1 study performed a subgroup analysis on this.5 This precluded data pooling for meta-analysis, and it was felt out with the scope of this review to pursue authors for original data. This data paucity is further observed when considering appendix pathology and its implications. Three authors reported an indication for appendicectomy (appendicitis vs other),5-7 with only 1 of these describing histological findings, albeit the data were incomplete, precluding data pooling and stratification. It is also important to consider up to 15% to 25% of appendicectomies performed for appendicitis as an indication return with normal pathology.8 This emphasizes the need for studies to focus on pathological examination, rather than on clinical indication. In the absence of accurate histopathology, the observed increased risk of colectomy in UC patients undergoing appendicectomy for appendicitis can be interpreted divergently. First, patients presenting with clinical appendicitis could be presenting either with acute appendicitis (unrelated to UC diagnosis) or with a periappendicular red patch in a skip lesion distribution. The latter may represent a more aggressive UC phenotype in itself. Without data describing such a pathology, these potential differences cannot be stratified for. As such, the results from the continuing COSTA (COlonic Salvage by Therapeutic Appendectomy) trial are eagerly awaited (NCT03912714). Alternatively, the observed greater risk of colectomy is not secondary to uncontrolled UC, but rather—and as proposed by this review—is a symptomatic improvement resulting in prolonged in vivo exposure to subclinical colonic inflammation with a subsequent risk of malignant transformation. Hence, it is the impetus for considering incorporating a history of appendicectomy into inflammatory bowel disease surveillance guidelines. Last, and as suggested by Dai and Huang's final point, some evidence suggests that the appendix acts as a microbiome storage site and may therefore contribute toward the maintenance of colonic bacterial homeostasis, reducing the risk of colonic carcinogenic progression following gastrointestinal tract insults.9 By removing the appendix, the homeostatic maintenance is lost and the risk of metaplastic progression is introduced, thereby increasing the risk of colectomy for colorectal cancer.9