Appendectomy and the development of ulcerative colitis

Gut, 2002

Background and aims: Recent studies on appendicectomy rates in ulcerative colitis and Crohn's disease have generally not addressed the effect of appendicectomy on disease characteristics. The aims of this study were to compare appendicectomy rates in Australian inflammatory bowel disease patients and matched controls, and to evaluate the effect of prior appendicectomy on disease characteristics. Methods: Patients were ascertained from the Brisbane Inflammatory Bowel Disease database. Controls matched for age and sex were randomly selected from the Australian Twin Registry. Disease characteristics included age at diagnosis, disease site, need for immunosuppression, and intestinal resection. Results: The study confirmed the significant negative association between appendicectomy and ulcerative colitis (odds ratio (OR) 0.23, 95% confidence interval (Cl) 0.14-0.38; p<0.0001) and found a similar result for Crohn's disease once the bias of appendicectomy at diagnosis was addressed (OR 0.34, 95% Cl 0.23-0.51; p<0.0001). Prior appendicectomy delayed age of presentation far both diseases and was statistically significant for Crohn's disease (p=0.02). In ulcerative colitis, patients with prior appendicectomy had clinically milder disease with reduced requirement for immunosuppression (OR 0.15, 95% Cl 0.02-1.15; p=0.04) and proctocolectomy (p=0.02) Conclusions: Compared with patients without prior appendicectomy, appendicectomy before diagnosis delays disease onset in ulcerative colitis and Crohn's disease and gives rise to a milder disease phenotype in ulcerative colitis. ********** Crohn's disease (CD) and ulcerative colitis (UC) represent the most common forms of idiopathic inflammatory bowel disease (IBD), with a prevalence of 0.2-0.5% within Caucasian populations. Both diseases are associated with episodes of acute or chronic inflammation affecting either the large bowel alone (UC) or both the small and large bowel (CD). (2) This intestinal inflammation is characterised by the presence of activated T and B lymphocytes and macrophages, and is thought to be an inappropriate response to local commensal bacteria. (3) Both genetic and environmental factors play a role in determining this response and after extensive research the first IBD susceptibility gene, Nod2, has been identified on chromosome 16. (4 5) Cigarette smoking remains the only environmental agent that has been confirmed as an independent risk factor. (6) Smoking is positively associated with the development of CD and can make the disease worse. In contrast, there is a significant protective effect of smoking on UC and nico tine patches have been used effectively to treat mild UC. ( ) More recently, there has been increasing interest in the role of the appendix on the development of IBD. There have now been 18 independent studies investigating this relationship of which 15 showed a highly significant negative association between appendicectomy and UC. (8-25) Patients with CD were similarly assessed in 10 of 18 studies, and although eight showed a positive association in only one study was this statistically significant. (8) At least two studies, one of which included both incident and prevalent cases, indicated that a significantly larger proportion of appendicectomies in patients with CD had been performed close to the time of diagnosis of the disease. (6 22) Two hypotheses have been generated from these studies which are not mutually exclusive. Firstly, patients who have an appendicectomy differ from those who develop UC in terms of genetic or environmental risk factors; and secondly, early appendicectomy modifies the intestinal immune response to protect against the development of UC. There is some support for the first hypothesis with a recent population based analysis indicating that only appendicectomy for inflammatory disorders (appendicitis or mesenteric adenitis) protects against the development of UC.(21) This study also confirmed the relevance of age at appendicectomy, with those individuals who had undergone surgery before 20 years gaining protection, as initially suggested by Duggan and colleagues.(17) However, there was no clear association between domestic hygiene, assessed by the prevalence of Helicobacter pylori serology and availability of hot running water, and the low rate of appendicectomy in UC patients." (11 17) Dec 2002 v51 i6 p808(6)

Diseases of the Colon & Rectum, 1999

PURPOSE: Appendectomy and cigarette smoking have been suggested to reduce the chance of developing ulcerative colitis. A case-control study was undertaken to determine the relative incidence of appendectomy in patients with ulcerative colitis. METHODS: This case-control stud}, examined the incidence of appendectomy in patients with ulcerative colitis and patients attending an orthopedic outpatient clinic. RESULTS: Of 100 patients with ulcerative colitis, 75 pairs were matched for age, gender, and cigarette smoking. The ulcerative colitis group had an appendectomy rate of 8 percent (6/75), compared with 21 percent in the control group (P = 0.018). The odds ratio was 3.5 (95 percent confidence interval, 1.15-10.6). CONCLUSIONS: No previous study has examined the effect of appendectomy, controlling for cigarette smoMng. This study confirms that appendectomy protects against or reduces the chance of development of ulcerative colitis. A possible immunological explanation for this effect is advanced. [Dijkstra B, Bagshaw PF, Frizelle FA. Protective effect of appendectomy on the development of ulcerative colitis: matched, case-control study. Dis Colon Rectum 1999;42: 334-336.

The American journal of gastroenterology, 2002

Appendectomy has been shown to protect against the development of ulcerative colitis. The objective of this study was to examine the effect of appendectomy on the clinical features and natural history of colitis. A total of 259 consecutive adults patients with ulcerative colitis were studied. Of the patients, 20 had undergone appendectomy (12 before onset of colitis and eight after diagnosis). The frequency of appendectomy was significantly less than in a group of 280 controls, which comprised partners of the patients and a group from the community (OR = 0.25; 95% CI = 0.14-0.44). This was even more significant if only the 12 patients who underwent surgery before the onset of colitis were considered (OR = 0.15; 95% CI = 0.07-0.28). Patients with prior appendectomy developed symptoms of ulcerative colitis for the first time at a significantly later age than those without appendectomy (42.5 +/- 6.5 vs 32.1 +/- 0.8 yr; p &lt; 0.01) or those who had appendectomy after the onset of colit...

BMC Surgery, 2015

Background: Over the past 20 years evidence has accumulated confirming the immunomodulatory role of the appendix in ulcerative colitis (UC). This led to the idea that appendectomy might alter the clinical course of established UC. The objective of this body of research is to evaluate the short-term and medium-term efficacy of appendectomy to maintain remission in patients with UC, and to establish the acceptability and cost-effectiveness of the intervention compared to standard treatment. Methods/Design: These paired phase III multicenter prospective randomised studies will include patients over 18 years of age with an established diagnosis of ulcerative colitis and a disease relapse within 12 months prior to randomisation. Patients need to have been medically treated until complete clinical (Mayo score <3) and endoscopic (Mayo score 0 or 1) remission. Patients will then be randomised 1:1 to a control group (maintenance 5-ASA treatment, no appendectomy) or elective laparoscopic appendectomy plus maintenance treatment. The primary outcome measure is the one year cumulative UC relapse rate-defined both clinically and endoscopically as a total Mayo-score ≥5 with endoscopic subscore of 2 or 3. Secondary outcomes that will be assessed include the number of relapses per patient at 12 months, the time to first relapse, health related quality of life and treatment costs, and number of colectomies in each arm. Discussion: The ACCURE and ACCURE-UK trials will provide evidence on the role and acceptability of appendectomy in the treatment of ulcerative colitis and the effects of appendectomy on the disease course.

Inflammatory Bowel Diseases, 2002

Besides a genetic predisposition, a causal role of various environmental factors has been considered in the etiology of ulcerative colitis (UC). The association between appendectomy and UC has recently been the subject of intense scrutiny in the hope that it may lead to the identification of important pathogenetic mechanisms. Published data from animal models of colitis demonstrated reduction in experimental colitis after appendectomy, especially if performed at an early age. Several epidemiological case control and cohort studies have shown a strong and consistent relationship. The metaanalysis of 17 case-controlled studies showed an overall odds ratio 0.312 (95% confidence intervals ‫ס‬ 0.261-0.373) in favor of appendectomy (p < 0.0001). One of the two recent large cohort studies is in agreement with these results, but the other failed to confirm them. All these studies have suggested that alterations in mucosal immune responses leading to appendicitis or resulting from appendectomy may negatively affect the pathogenetic mechanisms of UC. Further investigation of the role of appendectomy in UC is expected to open new fields for basic scientific research and may lead to the improvement of our understanding for the disease pathogenesis.

Gastroenterology, 1997

Colorectal Disease, 2012

Aim Previous studies have shown significantly lower appendectomy rates in ulcerative colitis (UC) patients compared with healthy controls. Evidence indicating that the appendix has an immunomodulatory role in UC has been accumulating. To examine the latest evidence on the effect of appendectomy on the disease course of UC.

Gastroenterology, 2003

Two common factors, cigarette smoking and appendectomy, have been found to play a role in ulcerative colitis (UC). Data on their role in the development of extraintestinal manifestations (EIM) are scarce.

Alimentary Pharmacology and Therapeutics, 2005

Background: The aetiology of inflammatory bowel disease remains largely unknown. Aim: We performed a comprehensive assessment of potential risk factors associated with the occurrence of inflammatory bowel disease. Methods: We identified a cohort of patients 20-84 years old between 1995 and 1997 registered in the General Practitioner Research Database in the UK. A total of 444 incident cases of IBD were ascertained and validated with the general practitioner. We performed a nested case-control analysis using all cases and a random sample of 10 000 frequency-matched controls. Results: Incidence rates for ulcerative colitis, Crohn's disease, and indeterminate colitis were 11, 8, and 2 cases per 100 000 person-years, respectively. Among women, we found that long-term users of oral contraceptives were at increased risk of developing UC (OR: 2.35; 95% CI: 0.89-6.22) and CD (OR: 3.15; 95% CI: 1.24-7.99). Similarly, long-term users of HRT had an increased risk of CD (OR: 2.60; 95% CI: 1.04-6.49) but not UC. Current smokers experienced a reduced risk of UC along with an increased risk of CD. Prior appendectomy was associated with a decreased the risk of UC (OR: 0.37; 95% CI: 0.14-1.00). Conclusions: Our results support the hypothesis of an increased risk of inflammatory bowel disease associated with oral contraceptives use and suggest a similar effect of hormone replacement therapy on CD. We also confirmed the effects of smoking and appendectomy on inflammatory bowel disease.

Gastroenterology, 2003

Background & Aims: Appendectomy is associated with a low risk of subsequent ulcerative colitis. This study analyzes the risk of Crohn's disease after appendectomy. Methods: We followed-up 212,218 patients with appendectomy before age 50 years and a cohort of matched controls, identified from the Swedish Inpatient Register and the nationwide Census, for any subsequent diagnosis of Crohn's disease. Results: An increased risk of Crohn's disease was found for more than 20 years after appendectomy, with incidence rate ratio 2.11 (95% confidence interval [CI], 1.21-3.79) after perforated appendicitis, 1.85 (95% CI, 1.10 -3.18) after nonspecific abdominal pain, 2.15 (95% CI, 1.25-3.80) after mesenteric lymphadenitis, 2.52 (95% CI, 1.43-4.63) after other diagnoses. After nonperforated appendicitis, there was an increased risk among women but not among men (incidence rate ratio 1.37; 95% CI, 1.03-1.85, respectively, 0.89, 95% CI, 0.64 -1.24). Patients operated on before age 10 years had a low risk (incidence rate ratio 0.48, 95% CI, 0.23-0.97). Crohn's disease patients with a history of perforated appendicitis had a worse prognosis. Conclusions: Appendectomy is associated with an increased risk of Crohn's disease that is dependent on the patient's sex, age, and the diagnosis at operation. The pattern of associations suggests a biologic cause.