Goodbye, Appendix. Hello, Crohn’s Disease?

— Meta-analysis finds a possible connection, although high heterogeneity was an issue

by
Ed Susman, Contributing Writer, MedPage Today
December 17, 2023

ORLANDO – People who undergo appendectomy may have an increased risk for the development of Crohn’s disease (CD), but not ulcerative colitis (UC), according to a systematic review and meta-analysis.

The meta-analysis showed a pooled OR of 1.57 (95% CI 1.01-2.43, P<0.00001) for CD in those who had gotten surgery of the mucosa-and-gut lymphoid tissue (MALT/GALT), reported Suprada Vinyak, MD, of Ballad Health in Norton, Virginia, at the Advances in Inflammatory Bowel Diseases annual meeting. However, Vinyak and colleagues cautioned in their poster that “substantial heterogeneity was observed (93%).”

In better news, there was a 40% reduction in risk for UC following MALT surgery (pooled OR 0.60, 95% CI 0.24-1.57, P<0.00001), they reported, although once again, there was a high level of heterogeneity (96%). Vinyak called the finding “surprising. To be honest, I can’t explain it. We were expecting both CD and UC to be associated with appendectomy.”

Daniel Waintraub, MD, of the Gastro Health Boca Raton and West Boca Medical Center in Florida, explained to MedPage Today that “often times, when people have imaging done for an IBD work-up, they [clinicians] will see inflammation in the right colon where the appendix is. Sometimes surgeons who are preparing for an appendectomy will see in their work-up some concomitant inflammation in the cecum where Crohn’s arises.”

“It is possible these are incidental findings, but to say what comes first – appendectomy or CD – is still an open question,” he said.

Waintraub, who was not involved in the study, said that “I have always considered the appendix as a vestigial organ that really doesn’t do anything in the body, but perhaps this information may show otherwise. This is interesting work, and certainly suggests we need more studies in this area.”

Vinyak told MedPage Today that “we got interested in this when we realized that with many of our patients with CD or with UC, the common denominator was an appendectomy. So we decided to look into this by doing medical literature searches.”

The researchers explained that MALT/GALT “play a pivotal role in immune regulation and gut microbiota balance. While dysbiosis [an imbalance in the gut microbiome] has been reported in IBD patients, a direct association remains unclear.”

They searched for appendectomies, MALT surgeries, and IBD, ultimately settling on 23 observational studies and six high-level evidentiary studies for the meta-analysis.

Vinyak said that the findings will contribute to a better understanding of the links between MALT surgery and IBD. She pointed out that “there are several unanswered questions. We don’t know from this study whether appendectomy preceded CD or vice versa, although that is something we are looking into in further work. We are also trying to work out the mechanisms of action that would cause one or the other.”