DISCUSSION
The nationwide cohort study indicated that the appendectomy cohort
exhibited a higher incidence rate of IBDs than did the comparison cohort
regardless of age, sex, and comorbidity. The appendectomy cohort had a
2.78-fold higher adjusted HR of IBDs (2.23-fold higher adjusted HR of UC
and 3.48-fold higher adjusted HR of CD) than did the comparison cohort.
Our results were comparable with a large case–control study, which
showed a 1.6 and 2.5 times higher risk of UC and CD after appendectomy
based on inpatient records from Veterans Affairs hospitals in the United
States [15].
Andersson et al. [14,16] reported that appendectomy is associated
with an increased CD risk but a decreased risk of subsequent UC through
an observational study of the Swedish Inpatient Registry. However, a
retrospective case–control study from 2 Chinese hospitals did not show
a significant negative association between appendectomy and UC
occurrence [17].
Although IBD prevalence is higher in Western countries than in Taiwan,
the incidence and prevalence of IBD have been rapidly increasing in
Taiwan [10,18,19]. The exact IBD pathogenesis remains to be
elucidated, although IBD is generally considered to be related to
genetic susceptibility and environmental factors [20,21]. Epigenetic
modifications influenced by gut microbiota and diet may pay a role in
IBD development [22,23]. Western-style diet may predispose people to
IBD [24]. Many people in Taiwan have shifted to a Western-style
diet, which may be associated with an increased IBD incidence in Taiwan
[25].
The vermiform appendix contains substantial lymphoid tissue and may act
as a microbial reservoir for beneficial microbes to reinoculate the gut
if required [6]. The appendix provides a complex microbial
environment for the homeostasis of immunologically and metabolically
active organs [26,27]. Therefore, the appendix may serve as an organ
to induce and maintain the mucosal immune system. An animal study
indicated that appendectomy impairs intestinal immunity, which may be
related to IBD development [28]. Gut microbiota alteration in IBD
may activate immune responses, interfere in homeostasis, cause tissue
injury, decrease the mucus layer, and enhance microbial penetration and
bacterial persistence in the gut tissue [29].
Anderson et al. conducted a cohort study by recruiting patients who
underwent appendectomy from the inpatient registry database of the
Swedish National Board of Health and Welfare and indicated that
appendectomy due to appendicitis is associated with a decreased risk of
subsequent UC [16]. In contrast, no significant risk difference of
UC was noted between appendectomy patients without inflammatory appendix
and non-appendecomy controls [16]. However, our study showed that
the appendectomy cohort had increased UC risk regardless of whether the
patient had appendicitis. Moreover, the UC risk was significantly higher
in the appendectomy cohort than the nonappendectomy cohort irrespective
of the age at appendectomy. The difference between Western studies and
our study may be due to racial variances and dysregulated gut microbiota
due to environmental insults [30].
The appendectomy cohort, irrespective of appendicitis, exhibited a
considerably increased CD risk compared with the nonappendectomy cohort.
The findings were consistent with those of previous studies [14]. In
addition, CD risk was significantly higher in the appendectomy cohort
than in the nonappendectomy cohort irrespective of the age at
appendectomy. The incidence rate of CD after appendectomy was the
highest in the first 3 years. The risk of subsequent CD in the
appendectomy cohort remained considerably higher than in the
nonappendectomy cohort after 6 years following appendectomy.
This longitudinal cohort study estimated the incidence and risk of IBD
in a large Asian population that underwent appendectomy. The study
cohort could be followed throughout the follow-up period through NHIRD
records because the NHI is mandatory and universal in Taiwan. However,
several limitations should be noted when interpreting the results.
First, coexistence of IBD and appendicitis was noted at appendectomy,
which would be diagnosed by the pathologist. Second, the Western dietary
habit of the study participants was not investigated in the current
study. However, we controlled for the comorbidities of hyperlipidemia,
diabetes, and hypertension to mediate the effect of a Western-style diet
[31,32]. Third, familial history of IBD in the study participants
was not available in the NHIRD, which may have influenced the study
results.
In summary, a nationwide cohort study indicated that the incidence and
risk of CD and UC are higher in the appendectomy cohort than in the
nonappendectomy cohort. The results highlight that clinicians must be
aware that Asian patients undergoing appendectomy may develop CD or UC.