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Naidu K, Wong P, Chapuis PH, Rickard MJFX, Ng KS. The Place of Appendicectomy in Inflammatory Bowel Disease-A Review. ANZ J Surg 2025. [PMID: 40372363 DOI: 10.1111/ans.70157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2024] [Revised: 04/07/2025] [Accepted: 04/16/2025] [Indexed: 05/16/2025]
Abstract
The aetiology and pathophysiology of inflammatory bowel disease (IBD) are not completely understood; however, a dysregulated intestinal immune system appears key to its pathogenesis. It has been suggested that the appendix is central to nurturing the enteric mucosal system due to its production of lymphoid products and that an appendicectomy may have an immune modulating effect. The aim of this review is to explore the available evidence for the association between IBD and appendicectomy and attempt to define its impact on the incidence and risk of Crohn's disease (CD) and Ulcerative colitis (UC) onset and progression.
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Affiliation(s)
- Krishanth Naidu
- Colorectal Surgery Unit, Concord Hospital, Concord, Australia
- Concord Institute of Academic Surgery, Concord Hospital, Concord, Australia
- Concord Clinical School, Clinical Sciences Building, Concord Hospital, University of Sydney, Concord, Australia
| | - Pearl Wong
- Colorectal Surgery Unit, Concord Hospital, Concord, Australia
- Concord Clinical School, Clinical Sciences Building, Concord Hospital, University of Sydney, Concord, Australia
| | - Pierre H Chapuis
- Colorectal Surgery Unit, Concord Hospital, Concord, Australia
- Concord Institute of Academic Surgery, Concord Hospital, Concord, Australia
- Concord Clinical School, Clinical Sciences Building, Concord Hospital, University of Sydney, Concord, Australia
| | - Matthew J F X Rickard
- Colorectal Surgery Unit, Concord Hospital, Concord, Australia
- Concord Institute of Academic Surgery, Concord Hospital, Concord, Australia
- Concord Clinical School, Clinical Sciences Building, Concord Hospital, University of Sydney, Concord, Australia
| | - Kheng-Seong Ng
- Colorectal Surgery Unit, Concord Hospital, Concord, Australia
- Concord Institute of Academic Surgery, Concord Hospital, Concord, Australia
- Concord Clinical School, Clinical Sciences Building, Concord Hospital, University of Sydney, Concord, Australia
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Conte M, Fournier A, Rothwell JA, Boutron-Ruault MC, Baglietto L, Fornili M, Sbidian E, Severi G. MALTectomy and psoriasis risk in women: A prospective study in the French E3N prospective cohort. PLoS One 2024; 19:e0310891. [PMID: 39556540 PMCID: PMC11573222 DOI: 10.1371/journal.pone.0310891] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Accepted: 09/09/2024] [Indexed: 11/20/2024] Open
Abstract
BACKGROUND AND AIM The involvement of mucosa associated lymphoid tissues (MALT) in the development of an autoimmune response in the skin is unclear and unstudied. In this study we sought to assess the relationship between removal of MALT tissues (MALTectomy) and the risk of development of psoriasis (overall or moderate-to-severe). METHODS We conducted a prospective observational study based on E3N, a French cohort composed of 98 995 women born between 1925 and 1950 and insured by the health insurance of the national education system (MGEN). The study population included the 90 119 women that completed the 1990 baseline questionnaire with available information on MALTectomy and a valid incident diagnostic date for psoriasis. During the 1990-2018 follow-up period 2 433 incident cases of psoriasis were identified through self-reports while during the period for which drug reimbursement data were available from the MGEN database (2004-2018), 120 cases of moderate-to-severe psoriasis were identified. Hazard ratios (HR) and their 95% confidence intervals were estimated by Cox proportional hazards models and adjusted for known or putative psoriasis risk factors. RESULTS Appendectomy was associated with an increased risk of psoriasis both in the univariate [HR: 1.17 (95% CI: 1.08-1.27)] and multivariable models [HR: 1.14 (95% CI: 1.05-1.24)]. A suggestive association with appendectomy was observed for moderate-to-severe psoriasis risk [univariate HR: 1.40 (95%CI: 0.97-2.02); multivariable HR: 1.36 (95%CI: 0.94-1.96)]. No association was observed between tonsillectomy or adenoidectomy both for overall and moderate-to-severe psoriasis. CONCLUSIONS The observed association between appendectomy and risk of psoriasis warrants further investigations as they may help to elucidate the disease etiology and improve risk prediction.
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Affiliation(s)
- Marco Conte
- UVSQ, Inserm, Gustave Roussy, Exposome and Heredity Team, Centre for Epidemiology and Population Health (CESP U1018), Université Paris-Saclay, Villejuif, France
| | - Agnes Fournier
- UVSQ, Inserm, Gustave Roussy, Exposome and Heredity Team, Centre for Epidemiology and Population Health (CESP U1018), Université Paris-Saclay, Villejuif, France
| | - Joseph A. Rothwell
- UVSQ, Inserm, Gustave Roussy, Exposome and Heredity Team, Centre for Epidemiology and Population Health (CESP U1018), Université Paris-Saclay, Villejuif, France
| | - Marie-Christine Boutron-Ruault
- UVSQ, Inserm, Gustave Roussy, Exposome and Heredity Team, Centre for Epidemiology and Population Health (CESP U1018), Université Paris-Saclay, Villejuif, France
| | - Laura Baglietto
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Marco Fornili
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Emilie Sbidian
- Department of Dermatology, Hôpital Henri Mondor, Créteil, France
- Epidemiology in Dermatology and Evaluation of Therapeutics (EpiDermE) ‐ EA 7379, Université Paris Est Créteil (UPEC), Créteil, France
| | - Gianluca Severi
- UVSQ, Inserm, Gustave Roussy, Exposome and Heredity Team, Centre for Epidemiology and Population Health (CESP U1018), Université Paris-Saclay, Villejuif, France
- Department of Statistics, Computer Science and Applications « G. Parenti », University of Florence, Italy
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Zhang Y, Yang L, Yuan L. Investigating the causal relationship between inflammatory bowel disease and simple appendicitis using Mendelian randomization. Sci Rep 2024; 14:23617. [PMID: 39384932 PMCID: PMC11464600 DOI: 10.1038/s41598-024-74572-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Accepted: 09/26/2024] [Indexed: 10/11/2024] Open
Abstract
The relationship between simple appendicitis and inflammatory bowel disease (IBD) is not clear. In this study, we approach the issue from a genetic perspective, using Mendelian randomization (MR) tools to explore the potential causal connection between the two. We used GWAS data from 12,882 IBD patients (21,770 controls), 5956 crohn's disease (CD) patients (14,927 controls), 6968 ulcerative colitis (UC) patients (20,464 controls), and 4604 simple appendicitis patients (481,880 controls). These statistical data were derived from a large-scale whole-genome association study of individuals with European ancestry. The primary analytical method for inferring the causal relationship between the conditions involved the use of the Inverse Variance Weighting (IVW) method as the main approach for bidirectional MR analysis. The MR analysis results predicted IBD was associated with a lower risk of simple appendicitis (OR: 0.947 (0.911, 0.984), p = 0.005). The results for CD (OR: 0.948 (0.916, 0.981), p = 0.002) and UC (OR: 0.954 (0.917, 0.992), p = 0.020) are consistent with this finding. In the reverse MR analysis, there is no significant association between simple appendicitis and the occurrence of IBD (p > 0.05), and the same holds true for CD and UC (p > 0.05). Our MR study results suggest a potential negative causal effect of IBD on the occurrence of simple appendicitis. Conversely, there does not appear to be a significant causal relationship between simple appendicitis and the risk of developing IBD.
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Affiliation(s)
- Yawei Zhang
- Department of General Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410011, China
| | - Lichao Yang
- Department of General Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410011, China.
| | - Lianwen Yuan
- Department of General Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410011, China.
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Thacker N, Duncanson K, Eslick GD, Dutt S, O'Loughlin EV, Hoedt EC, Collins CE. Antibiotics, passive smoking, high socioeconomic status and sweetened foods contribute to the risk of paediatric inflammatory bowel disease: A systematic review with meta-analysis. J Pediatr Gastroenterol Nutr 2024; 79:610-621. [PMID: 39020449 DOI: 10.1002/jpn3.12303] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Revised: 05/27/2024] [Accepted: 06/05/2024] [Indexed: 07/19/2024]
Abstract
OBJECTIVE Genetic and environmental factors influence pathogenesis and rising incidence of paediatric inflammatory bowel disease (PIBD). The aim was to meta-analyse evidence of diet and environmental factors in PIBD. METHODS A systematic search was conducted to identify diet and environmental factors with comparable risk outcome measures and had been reported in two or more PIBD studies for inclusion in meta-analyses. Those with ≥2 PIBD risk estimates were combined to provide pooled risk estimates. RESULTS Of 4763 studies identified, 36 studies were included. PIBD was associated with higher risk with exposure to ≥/=4 antibiotic courses (includes prescriptions/purchases/courses), passive smoking, not being breastfed, sugary drink intake, being a non-Caucasian child living in a high-income country and infection history (odds ratio [OR] range: 2-3.8). Paediatric Crohn's disease (CD) was associated with higher risk with exposure to antibiotics during early childhood, ≥/=4 antibiotic courses, high socioeconomic status (SES), maternal smoking, history of atopic conditions and infection history (OR range: 1.6-4.4). A history of infection was also associated with higher risk of paediatric ulcerative colitis (UC) (OR: 3.73). Having a higher number of siblings (≥2) was associated with lower risk of paediatric CD (OR: 0.6) and paediatric UC (OR: 0.7). Pet exposure was associated with lower risk of paediatric UC (OR: 0.5). CONCLUSION Several factors associated with PIBD risk were identified that could potentially be used to develop a disease screening tool. Future research is needed to address risk reduction in PIBD.
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Affiliation(s)
- Nisha Thacker
- School of Health Sciences, College of Health Medicine and Wellbeing, The University of Newcastle, Sydney, New South Wales, Australia
- Food and Nutrition Research Program, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia
| | - Kerith Duncanson
- Food and Nutrition Research Program, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia
- School of Medicine and Public Health, College of Health Medicine and Wellbeing, The University of Newcastle, Sydney, New South Wales, Australia
- NHMRC Centre of Research Excellence in Digestive Health, The University of Newcastle, Sydney, New South Wales, Australia
| | - Guy D Eslick
- NHMRC Centre of Research Excellence in Digestive Health, The University of Newcastle, Sydney, New South Wales, Australia
| | - Shoma Dutt
- Department of Gastroenterology, The Children's Hospital at Westmead, Sydney Children's Hospital Network, Westmead, New South Wales, Australia
- Children's Hospital at Westmead Clinical School, Sydney Medical Program, University of Sydney, Sydney, New South Wales, Australia
| | - Edward V O'Loughlin
- Department of Gastroenterology, The Children's Hospital at Westmead, Sydney Children's Hospital Network, Westmead, New South Wales, Australia
| | - Emily C Hoedt
- NHMRC Centre of Research Excellence in Digestive Health, The University of Newcastle, Sydney, New South Wales, Australia
- School of Biomedical Sciences and Pharmacy, College of Health Medicine and Wellbeing, The University of Newcastle, Sydney, New South Wales, Australia
| | - Clare E Collins
- School of Health Sciences, College of Health Medicine and Wellbeing, The University of Newcastle, Sydney, New South Wales, Australia
- Food and Nutrition Research Program, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia
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Amin R, Mansabdar A, Gu H, Gangineni B, Mehta N, Patel H, Patel N, Laller S, Vinayak S, Abdulqader MA, Jain H, Rekhraj AS, Adimoulame H, Singh G, Moonjely Davis J, Patel U, Gill H. Mucosa-Associated Lymphoid Tissue Surgeries as a Possible Risk for Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis. Gastroenterology Res 2024; 17:90-99. [PMID: 38716286 PMCID: PMC11073456 DOI: 10.14740/gr1672] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2023] [Accepted: 03/27/2024] [Indexed: 01/06/2025] Open
Abstract
BACKGROUND Inflammatory bowel disease (IBD) is a group of chronic inflammatory gastrointestinal disorders that are caused by genetic susceptibility and environmental factors and affects a significant portion of the global population. The gut-associated lymphoid tissue (GALT) is known to play a crucial role in immune modulation and maintaining gut microbiota balance. Dysbiosis in the latter has a known link to IBD. Therefore, the increasing prevalence of adenoidectomy in children should be explored for its potential association with IBD. The objective of this paper was to assess the association between adenoid tissue removal and the risk of developing Crohn's disease (CD) and ulcerative colitis (UC). METHODS We conducted a pooled meta-analysis to evaluate the extended clinical outcomes in patients who underwent appendicectomy and tonsillectomy compared to those who did not. Our approach involved systematically searching the PubMed database for relevant observational studies written in English. We followed the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines to collect data from various time periods, and to address the diversity in study results; we employed a random-effects analysis that considered heterogeneity. For outcomes, odds ratios (ORs) were pooled using a random-effects model. RESULTS Seven studies, out of a total of 114,537, met our inclusion criteria. Our meta-analysis revealed a significant association between appendicectomy and CD (OR: 1.57; 95% confidence interval (CI): 1.01 - 2.43; heterogeneity I2 = 93%). Similarly, we found a significant association between tonsillectomy and CD (OR: 1.93; 95% CI: 0.96 - 3.89; I2 = 62%). However, no significant association was observed between appendicectomy and UC (OR: 0.60; 95% CI: 0.24 - 1.47; I2 = 96%), while a modest association was found between tonsillectomy and UC (OR: 1.24; 95% CI: 1.18 - 1.30; I2 = 0%). CONCLUSIONS In summary, we found that the trend of appendicectomy is linked to higher odds of CD, and tonsillectomy is more likely associated with increased odds for both CD and UC, with a risk of bias present.
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Affiliation(s)
- Rutvi Amin
- Department of Medicine, Surat Municipal Institute of Medical Education and Research, Surat, Gujarat 395010, India
| | - Aditya Mansabdar
- Department of Medicine, First Faculty of Medicine, Charles University, Prague 12108, Czechia
| | - Hyundam Gu
- Department of Internal Medicine, Yeouido St. Mary’s Hospital, The Catholic University of Korea College of Medicine, Seoul 07345, Korea
| | - Bhavani Gangineni
- Department of Internal Medicine, Guntur Medical College, Guntur, Andhra Pradesh 522004, India
| | - Neev Mehta
- Department of Medicine, Lahey Hospital and Medical Center, Burlington, MA 01805, USA
| | - Harini Patel
- Department of Medicine, Gujarat Medical Educational and Research Society (GMERS), Himmatnagar, Gujarat 383001, India
| | - Neel Patel
- Department of Public Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Srishti Laller
- Department of Internal Medicine, Sutter Roseville Medical Center, Roseville, CA 95661, USA
| | - Suprada Vinayak
- Department of Internal Medicine, Wellmont Health Systems/Ballad Health, VA 24273, USA
| | | | | | | | - Harshini Adimoulame
- Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry 605006, India
| | - Gurinder Singh
- Department of Clinical and Medical Sciences, Universidad Especializada de las Americas, Panama 0849-0141, Panama
| | | | - Urvish Patel
- Department of Public Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Harmeet Gill
- Department of Medicine, HopeHealth, Florence, SC 29501, USA
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Zhang L, Hu C, Zhang Z, Liu R, Liu G, Xue D, Wang Z, Wu C, Wu X, She J, Shi F. Association between prior appendectomy and the risk and course of Crohn's disease: A systematic review and meta-analysis. Clin Res Hepatol Gastroenterol 2023; 47:102090. [PMID: 36746236 DOI: 10.1016/j.clinre.2023.102090] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Revised: 01/25/2023] [Accepted: 01/31/2023] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS The appendix has an important immune function in both health and disease, and appendectomy may influence microbial ecology and immune function. This meta-analysis aims to assess the association between appendectomy and the risk and course of Crohn's disease (CD). METHODS PubMed, EMBASE, and the Cochrane Library were used to identify all studies published until June 2022. Data from studies evaluating the association between appendectomy and CD were reviewed. RESULTS A total of 28 studies were included in the final analysis, comprising 22 case-control and 6 cohort studies. A positive relationship between prior appendectomy and the risk of developing CD was observed in both case-control studies (odds ratio [OR]: 1.59, 95% confidence interval [CI]: 1.22-2.08) and cohort studies (relative risk [RR]: 2.28, 95% CI: 1.66-3.14). The elevated risk of CD persisted 5 years post-appendectomy (RR = 1.24, 95% CI: 1.12-1.36). The risk of developing CD was similarly elevated regardless of the presence (RR = 1.64, 95% CI: 1.17-2.31) or absence (RR = 2.77, 95% CI: 1.84-4.16) of appendicitis in patients. Moreover, significant differences were found in the proportion of terminal ileum lesions (OR = 1.63; 95% CI: 1.38-1.93) and colon lesions (OR = 0.70; 95% CI: 0.5-0.84) between CD patients with appendectomy and those without appendectomy. CONCLUSIONS The risk of developing CD following an appendectomy is significant and persists 5 years postoperatively. Moreover, the elevated risk of CD may mainly occur in the terminal ileum.
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Affiliation(s)
- Lei Zhang
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China; Center for Gut Microbiome Research, Med-X Institute, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Chenhao Hu
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China; Center for Gut Microbiome Research, Med-X Institute, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Zhe Zhang
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China; Center for Gut Microbiome Research, Med-X Institute, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Ruihan Liu
- Center for Gut Microbiome Research, Med-X Institute, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Gaixia Liu
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China; Center for Gut Microbiome Research, Med-X Institute, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Dong Xue
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China; Center for Gut Microbiome Research, Med-X Institute, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Zhe Wang
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China; Center for Gut Microbiome Research, Med-X Institute, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Chenxi Wu
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China; Center for Gut Microbiome Research, Med-X Institute, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Xuefu Wu
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China; Center for Gut Microbiome Research, Med-X Institute, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Junjun She
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China; Center for Gut Microbiome Research, Med-X Institute, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
| | - Feiyu Shi
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China; Center for Gut Microbiome Research, Med-X Institute, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
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Maret-Ouda J, Ström JC, Roelstraete B, Emilsson L, Joshi AD, Khalili H, Ludvigsson JF. Appendectomy and Future Risk of Microscopic Colitis: A Population-Based Case-Control Study in Sweden. Clin Gastroenterol Hepatol 2023; 21:467-475.e2. [PMID: 35716902 DOI: 10.1016/j.cgh.2022.05.037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Revised: 05/24/2022] [Accepted: 05/24/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS Microscopic colitis (MC) is an inflammatory bowel disease and a common cause of chronic diarrhea. Appendectomy has been suggested to have immunomodulating effects in the colon, influencing the risk of gastrointestinal disease. The relationship between appendectomy and MC has only been sparsely studied. METHODS This was a case-control study based on the nationwide ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden) cohort, consisting of histopathological examinations in Sweden, linked to national registers. Patients with MC were matched to population controls by age, sex, calendar year of biopsy, and county of residence. Data on antecedent appendectomy and comorbidities were retrieved from the Patient Register. Unconditional logistic regression models were conducted presenting odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for country of birth and matching factors. Further subanalyses were made based on MC subtypes (lymphocytic colitis and collagenous colitis), follow-up time postappendectomy and severity of appendicitis. RESULTS The study included 14,520 cases of MC and 69,491 controls, among these 7.6% (n = 1103) and 5.1% (n = 3510), respectively, had a previous appendectomy ≥1 year prior to MC or matching date. Patients with a previous appendectomy had an increased risk of MC in total (OR, 1.50; 95% CI, 1.40-1.61) and per the collagenous colitis subtype (OR, 1.67; 95% CI, 1.48-1.88) or lymphocytic colitis subtype (OR, 1.42; 95% CI, 1.30-1.55). The risk remained elevated throughout follow-up, and the highest risk was observed in noncomplicated appendicitis. CONCLUSIONS This nationwide case-control study found a modestly increased risk of developing MC following appendectomy.
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Affiliation(s)
- John Maret-Ouda
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Centre for Clinical Research Sörmland, Uppsala University, Eskilstuna, Sweden.
| | - Jennifer C Ström
- Centre for Clinical Research Sörmland, Uppsala University, Eskilstuna, Sweden
| | - Bjorn Roelstraete
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Louise Emilsson
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; School of Medical Science, University of Örebro, Örebro, Sweden; Värmlands Nysäter Health Care Center and Centre for Clinical Research, County Council of Värmland, Karlstad, Sweden; Department of General Practice, Institute of Health and Society, University of Oslo, Oslo, Norway
| | - Amit D Joshi
- Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Gastroenterology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachussets
| | - Hamed Khalili
- Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Gastroenterology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachussets; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, Massachussets
| | - Jonas F Ludvigsson
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York; Department of Paediatrics, Örebro University Hospital, Örebro, Sweden
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Hellsing C, Örtqvist AK, Hagel E, Mesas‐Burgos C, Gustafsson UO, Granström AL. Delivery mode and risk of gastrointestinal disease in the offspring. Acta Obstet Gynecol Scand 2022; 101:1146-1152. [PMID: 35924371 PMCID: PMC9812198 DOI: 10.1111/aogs.14427] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Revised: 05/25/2022] [Accepted: 06/24/2022] [Indexed: 01/07/2023]
Abstract
INTRODUCTION The global increase of individuals born by cesarean section with reported levels up to 20% of all deliveries, makes it important to study cesarean section and possible associations that can increase risk of subsequent diseases in children. The aim of the study was to evaluate if cesarean section is associated with increased risk of gastrointestinal disease later in life in a large population-based cohort. MATERIAL AND METHODS In this national population-based cohort study including all full-term individuals registered in the Medical Birth Register in Sweden between 1990 and 2000, type of delivery (exposure) was collected from the Medical Birth Register. The study population was followed until 2017 with regards to the outcomes: inflammatory bowel disease (Crohn's disease or ulcerative colitis), appendicitis, cholecystitis, or diverticulitis registered in the Swedish National Patient Register. Cox proportional-hazards models compared disease-free survival time between exposed and unexposed. RESULTS The final study population consisted of 1 102 468 individuals of whom 11.6% were delivered by cesarean section and 88.4% were vaginally delivered. In univariate analysis, cesarean section was associated with Crohn's disease (hazard ratio [HR] 1.13, 95% confidence interval [CI] 1.02-1.25), diverticulosis (HR 1.57, 95% CI 1.13-2.18), and cholecystitis (HR 1.16, 95% CI 1.05-1.28). However, the increased risk only remained for Crohn's disease after adjustment for confounders (HR 1.14, 95% CI 1.02-1.27). No associations between delivery mode and appendicitis, ulcerative colitis, cholecystitis, or diverticulosis were found in the multivariate analysis. CONCLUSIONS Cesarean section is associated with Crohn's disease later in life, but no other association between delivery mode and gastrointestinal disorders later in life could be found.
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Affiliation(s)
- Christine Hellsing
- Department of Surgery, Danderyd Hospital & Department of Clinical SciencesDanderyd Hospital, Karolinska InstitutetStockholmSweden
| | - Anne K. Örtqvist
- Clinical Epidemiology Unit, Department of MedicineKarolinska InstitutetStockholmSweden,Department of Obstetrics and GynecologyVisby County HospitalVisbySweden
| | - Eva Hagel
- Department of Learning, Informatics, Management and Ethics, Unit for Medical StatisticsKarolinska InstituteStockholmSweden
| | - Carmen Mesas‐Burgos
- Department of Women's and Children's HealthKarolinska InstitutetStockholmSweden,Division of Pediatric SurgeryAstrid Lindgren Children's Hospital, Karolinska University HospitalStockholmSweden
| | - Ulf O. Gustafsson
- Department of Surgery, Danderyd Hospital & Department of Clinical SciencesDanderyd Hospital, Karolinska InstitutetStockholmSweden
| | - Anna Löf Granström
- Department of Surgery, Danderyd Hospital & Department of Clinical SciencesDanderyd Hospital, Karolinska InstitutetStockholmSweden,Department of Women's and Children's HealthKarolinska InstitutetStockholmSweden,Division of Pediatric SurgeryAstrid Lindgren Children's Hospital, Karolinska University HospitalStockholmSweden
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Kiasat A, Ekström LD, Marsk R, Löf‐Granström A, Gustafsson UO. Childhood appendicitis and future risk of inflammatory bowel disease - A nationwide cohort study in Sweden 1973-2017. Colorectal Dis 2022; 24:975-983. [PMID: 35344255 PMCID: PMC9545649 DOI: 10.1111/codi.16128] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2021] [Revised: 02/08/2022] [Accepted: 02/12/2022] [Indexed: 02/08/2023]
Abstract
AIM The aim of this study was to investigate the association between juvenile appendicitis, treated conservatively or with appendectomy, and adult risk of inflammatory bowel disease (IBD), either ulcerative colitis (UC) or Crohn's disease (CD). We used nationwide population data from more than 100,000 individuals followed for over four decades. METHOD All Swedish patients discharged with a diagnosis of appendicitis before the age of 16 years between 1973 to 1996 were identified. Everyone diagnosed with appendicitis was matched to an individual in the general population without a history of juvenile appendicitis (unexposed) of similar age, sex and region of residence. The study population was retrospectively followed until 2017 for any development of UC or CD. Cox proportional-hazards models compared disease-free survival time between exposed and unexposed individuals, also analysing the impact of treatment (conservative treatment versus appendectomy). RESULTS The final cohort consisted of 52,391 individuals exposed to appendicitis (1,674,629 person years) and 51,415 unexposed individuals (1,638,888 person years). Childhood appendicitis with appendectomy was associated with a significantly lower risk of adult IBD [adjusted hazard ratio (aHR) 0.48 (0.42-0.55)], UC [aHR 0.30 (0.25-0.36)] and CD [aHR 0.82 (0.68-0.97)]. Those treated conservatively had a lower risk of adult UC [aHR 0.29 (0.12-0.69)] but not CD [aHR 1.12 (0.61-2.06)] compared with unexposed individuals. CONCLUSION Juvenile appendicitis treated with appendectomy was associated with a decreased risk of adult IBD, both UC and CD. Those treated conservatively instead of with surgery had a lower risk of UC only. Our findings warrant more research on the role of the appendix and gut microbiota in the pathogenesis of IBD.
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Affiliation(s)
- Ali Kiasat
- Department of SurgeryDanderyd Hospital and Department of Clinical Sciences, Danderyd Hospital, Karolinska InstitutetStockholmSweden
| | - Lucas D. Ekström
- Department of Medicine, Solna, Clinical Epidemiology UnitKarolinska InstitutetStockholmSweden
| | - Richard Marsk
- Department of SurgeryDanderyd Hospital and Department of Clinical Sciences, Danderyd Hospital, Karolinska InstitutetStockholmSweden
| | - Anna Löf‐Granström
- Department of SurgeryDanderyd Hospital and Department of Clinical Sciences, Danderyd Hospital, Karolinska InstitutetStockholmSweden,Department of Women's and Children's HealthKarolinska InstitutetStockholmSweden
| | - Ulf O. Gustafsson
- Department of SurgeryDanderyd Hospital and Department of Clinical Sciences, Danderyd Hospital, Karolinska InstitutetStockholmSweden
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10
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Welsh S, Sam Z, Seenan JP, Nicholson GA. The Role of Appendicectomy in Ulcerative Colitis: Systematic Review and Meta-Analysis. Inflamm Bowel Dis 2022; 29:633-646. [PMID: 35766795 DOI: 10.1093/ibd/izac127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Indexed: 12/09/2022]
Abstract
BACKGROUND This updated systematic review and meta-analysis investigates the putative role of the appendix in ulcerative colitis as a therapeutic target. METHODS Ovid Medline, Embase, PubMed and CENTRAL were searched with MeSH terms ("appendectomy" OR "appendicitis" OR "appendix") AND ("colitis, ulcerative") through October 2020, producing 1469 references. Thirty studies, including 118 733 patients, were included for qualitative synthesis and 11 for quantitative synthesis. Subgroup analysis was performed on timing of appendicectomy. Results are expressed as odds ratio (OR) with 95% confidence intervals (CIs). RESULTS Appendicectomy before UC diagnosis reduces the risk of future colectomy (OR, 0.76; 95% CI, 0.65-0.89; I2 = 5%; P = .0009). Corresponding increased risk of colorectal cancer and high-grade dysplasia are identified (OR, 2.27; 95% CI, 1.11-4.66; P = .02). Significance is lost when appendicectomy is performed after disease onset. Appendicectomy does not affect hospital admission rates (OR, 0.87; 95% CI, 0.68-1.12; I2 = 93%; P = .27), steroid use (OR, 1.08; 95% CI, 0.78-1.49; I2 = 36%; P = .64), immunomodulator use (OR, 1.04; 95% CI, 0.76-1.42; I2 = 19%; P = .79), or biological therapy use (OR, 0.76; 95% CI, 0.44-1.30; I2 = 0%; P = .32). Disease extent and risk of proximal progression are unaffected by appendicectomy. The majority (71% to 100%) of patients with refractory UC avoid colectomy following therapeutic appendicectomy at 3-year follow-up. CONCLUSIONS Prior appendicectomy reduces risk of future colectomy. A reciprocal increased risk of CRC/HGD may be due to prolonged exposure to subclinical colonic inflammation. The results warrant further research, as consideration may be put toward incorporating a history of appendicectomy into IBD surveillance guidelines. A potential role for therapeutic appendicectomy in refractory left-sided UC is also identified.
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Affiliation(s)
- Silje Welsh
- Edinburgh Medical School: Clinical Sciences, University of Edinburgh, Edinburgh, Scotland.,General Surgery and Gastroenterology Department, NHS Greater Glasgow & Clyde, Glasgow, Scotland
| | - Zihao Sam
- Edinburgh Medical School: Clinical Sciences, University of Edinburgh, Edinburgh, Scotland.,General Surgery and Gastroenterology Department, NHS Greater Glasgow & Clyde, Glasgow, Scotland
| | - John Paul Seenan
- General Surgery and Gastroenterology Department, NHS Greater Glasgow & Clyde, Glasgow, Scotland.,Medical School, University of Glasgow, Glasgow, Scotland
| | - Gary A Nicholson
- General Surgery and Gastroenterology Department, NHS Greater Glasgow & Clyde, Glasgow, Scotland.,Medical School, University of Glasgow, Glasgow, Scotland
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11
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Song MY, Ullah S, Yang HY, Ahmed MR, Saleh AA, Liu BR. Long-term effects of appendectomy in humans: is it the optimal management of appendicitis? Expert Rev Gastroenterol Hepatol 2021; 15:657-664. [PMID: 33350352 DOI: 10.1080/17474124.2021.1868298] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Appendectomy remains the gold standard for treating uncomplicated and complicated appendicitis. However, the vermiform appendix may play a significant role in the immune system (secondary immune function) and maintain a reservoir of the normal microbiome for the human body. The aim of this study was to summarize the long-term effects after appendectomy and discuss whether appendectomy is suitable for all appendicitis patients. AREAS COVERED A comprehensive and unbiased literature search was performed in PubMed. The terms 'appendix,' 'appendicitis,' 'appendectomy,' and 'endoscopic retrograde appendicitis therapy' were searched in the title and/or abstract. This review summarizes the long-term effects of appendectomy on some diseases in humans and describes three methods including appendectomy, medical treatment, and an 'organ-sparing' technique, named endoscopic retrograde appendicitis therapy (ERAT) to treat appendicitis. EXPERT OPINION Appendectomy remains the first-line therapy for appendicitis. The patient's problem is appendix, not appendicitis. If we treat appendicitis, the problem should be resolved. During COVID-19, an initial antibiotic treatment of mild appendicitis represents a promising strategy. For patients who are worried about the long-term adverse effect after appendectomy and have a strong desire to preserve the appendix and are aware of the risk of appendicitis recurrence, medical treatment, or ERAT could be proposed.
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Affiliation(s)
- Ming-Yang Song
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,The Academy of Medical Science, Zhengzhou University, Zhengzhou, China
| | - Saif Ullah
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Hui-Yu Yang
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Md Robin Ahmed
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | | | - Bing-Rong Liu
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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12
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Loureiro ACCF, Barbosa LER. Appendectomy and Crohn's Disease. JOURNAL OF COLOPROCTOLOGY 2019; 39:373-380. [DOI: 10.1016/j.jcol.2017.12.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
Abstract
Abstract
Introduction Crohn's Disease is a chronic and idiopathic inflammatory process with transmural invasion that can affect the entire gastrointestinal tract. The etiopathogenesis of this pathology is not fully understood and studies have been carried out to understand the influence of different kind of factors on its development, including appendectomy. This monograph aims to address the possible existence of a link between appendectomy and Crohn's Disease, and the possible causes and clinical consequences of this association.
Methods This monograph was based on the research of original scientific articles in MEDLINE database via PubMed, restricted to articles in Portuguese and English during the period between 1991 and 2017.
Results Appendectomy seems positively associated with the development of Crohn's Disease, especially in the first years of surgery, regardless of whether or not there is inflammation of the appendix. In fact, the appendix plays important roles in gastrointestinal integrity, acting in the development of an adequate immune response, maintaining and regulating the intestinal flora.
Conclusion The appendix is important for intestinal homeostasis, preventing the development of certain pathologies. Its resection, regardless of whether or not there is an inflammation after surgery, increases the risk of Crohn's Disease and worsens the prognosis of this pathology, so appendectomy should be avoided in the absence of appendicitis.
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Affiliation(s)
| | - Laura Elisabete Ribeiro Barbosa
- Universidade do Porto, Faculdade de Medicina, Porto, Portugal
- Centro Hospitalar São João, Serviço de Cirurgia Geral, Porto, Portugal
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13
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Abstract
Ulcerative colitis (UC) is a known risk factor for colorectal cancer, but the association between UC and appendiceal adenocarcinoma remains rare. We present a 42-year-old patient with long-standing UC who presented with acute appendicitis shortly after a routine colonoscopy. Histopathological examination revealed moderately differentiated appendiceal adenocarcinoma. The recognition of appendiceal cancer as a complication of long-standing UC warrants increased clinical awareness.
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14
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Choi HG, Oh DJ, Kim M, Kim S, Min C, Kong IG. Appendectomy and rheumatoid arthritis: A longitudinal follow-up study using a national sample cohort. Medicine (Baltimore) 2019; 98:e17153. [PMID: 31577706 PMCID: PMC6783172 DOI: 10.1097/md.0000000000017153] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
The present study evaluated the association between appendectomy and rheumatoid arthritis (RA) using a national sample cohort of the Korean population. In this cohort study, the Korean National Health Insurance Service-National Sample Cohort of individuals ≥20 years old was collected from 2002 to 2013. A total of 14,995 appendectomy participants were 1:4 matched with 59,980 control subjects for age, group, sex, income group, region of residence, hypertension, diabetes, and dyslipidemia. We analyzed the occurrence of RA in both the appendectomy and control groups. Appendectomies were identified using operation codes for appendicitis only. RA was defined by International Classification of Disease-10 codes (M05 or M06) and medication histories. Crude and adjusted hazard ratios (HRs) were analyzed using a stratified Cox proportional hazard model. Subgroup analyses were performed on groups stratified by age and sex. The adjusted HR for RA was 1.02 (95% confidence interval = 0.76-1.38) in the appendectomy group (P = .883). In all of the subgroup analyses according to age and sex, the adjusted HRs for RA were not higher in the appendectomy group than those in the control group. We could not identify any significant relationship between appendectomy and RA.
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Affiliation(s)
- Hyo Geun Choi
- Department of Otorhinolaryngology-Head & Neck Surgery, Hallym University College of Medicine, Anyang
| | - Dong Jun Oh
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul
| | - Miyoung Kim
- Department of Laboratory Medicine, Hallym University College of Medicine, Anyang
| | - Sunmi Kim
- Department of Family Medicine, Kangwon National University College of Medicine, Chuncheon, Gangwon-do
| | - Chanyang Min
- Hallym Data Science Laboratory, Hallym University College of Medicine, Anyang
- Graduate School of Public Health, Seoul National University
| | - Il Gyu Kong
- Department of Otorhinolaryngology-Head & Neck Surgery, Hallym University College of Medicine, Anyang
- Department of Otorhinolaryngology-Head and Neck Surgery, National Medical Center, Seoul, Korea
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15
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Prior Appendectomy and the Onset and Course of Crohn's Disease in Chinese Patients. Gastroenterol Res Pract 2019; 2019:8463926. [PMID: 31396275 PMCID: PMC6664542 DOI: 10.1155/2019/8463926] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2019] [Revised: 04/21/2019] [Accepted: 04/24/2019] [Indexed: 12/15/2022] Open
Abstract
Background and Aim The relationship between prior appendectomy and Crohn's disease (CD) has previously revealed conflicting findings. The present study investigates the relationship between prior appendectomy and CD development in Chinese patients. Methods A retrospective case-control study was performed to compare prior appendectomy rate between CD patients and age- and gender-matched controls at two Chinese hospitals. The clinical course of CD was determined in patients who underwent and did not undergo appendectomies before CD diagnosis. Results A total of 617 CD patients and 617 controls were included. The appendectomy rate before CD diagnosis in patients was higher, when compared to controls (6.65% versus 3.73%, P = 0.033). Appendectomy was a risk factor for the onset of CD independent of smoking in the multivariate analysis (OR: 1.878; 95% CI: 1.111–3.174; P = 0.019). Appendectomies were performed closer to the date of CD diagnosis in the trend test (P = 0.039). The rate of appendectomy within one year or 1-5 years before CD diagnosis was higher in patients when compared to that in controls (0.97% versus 0%, P = 0.031; 1.13% versus 0.32%, P = 0.180). However, the rate of appendectomy over five years before CD diagnosis was close to controls (4.54% versus 3.40%, P = 0.392). No significant differences in disease location, behavior, medication, and intestinal resection between appendectomy and nonappendectomy CD patients were found, even in the subgroup analysis by age of appendectomy. Conclusion Prior appendectomy is a risk factor for the onset of CD. However, the appendectomy rate only increased for a short duration before CD diagnosis, likely reflecting a diagnostic bias. Prior appendectomy did not influence the features or course of CD.
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16
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Girard-Madoux MJ, Gomez de Agüero M, Ganal-Vonarburg SC, Mooser C, Belz GT, Macpherson AJ, Vivier E. The immunological functions of the Appendix: An example of redundancy? Semin Immunol 2018; 36:31-44. [DOI: 10.1016/j.smim.2018.02.005] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2018] [Accepted: 02/16/2018] [Indexed: 12/12/2022]
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Abstract
Inflammatory bowel diseases consisting of Crohn's disease and ulcerative colitis are chronic inflammatory diseases of the gastrointestinal tract. In addition to genetic susceptibility and disturbances of the microbiome, environmental exposures forming the exposome play an important role. Starting at birth, the cumulative effect of different environmental exposures combined with a predetermined genetic susceptibility is thought to cause inflammatory bowel disease. All these environmental factors are part of a Western lifestyle, suiting the high incidence rates in Europe and the United States. Whereas receiving breastfeeding, evidence of a Helicobacter pylori infection and vitamin D are important protective factors in Crohn's disease as well as ulcerative colitis, increased hygiene, experiencing a bacterial gastroenteritis in the past, urban living surroundings, air pollution, the use of antibiotics, nonsteroidal anti-inflammatory drugs, and oral contraceptives are likely to be the most important risk factors for both diseases. Current cigarette smoking yields a divergent effect by protecting against ulcerative colitis but increasing risk of Crohn's disease, whereas former smoking increases chances of both diseases. This review gives a clear overview of the current state of knowledge concerning the exposome. Future studies should focus on measuring this exposome yielding the possibility of combining all involved factors to one exposome risk score and our knowledge on genetic susceptibility.
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18
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Feenstra B, Bager P, Liu X, Hjalgrim H, Nohr EA, Hougaard DM, Geller F, Melbye M. Genome-wide association study identifies variants in HORMAD2 associated with tonsillectomy. J Med Genet 2016; 54:358-364. [PMID: 27941131 DOI: 10.1136/jmedgenet-2016-104304] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2016] [Revised: 11/09/2016] [Accepted: 11/10/2016] [Indexed: 11/03/2022]
Abstract
BACKGROUND Inflammation of the tonsils is a normal response to infection, but some individuals experience recurrent, severe tonsillitis and massive hypertrophy of the tonsils in which case surgical removal of the tonsils may be considered. OBJECTIVE To identify common genetic variants associated with tonsillectomy. METHODS We used tonsillectomy information from Danish health registers and carried out a genome-wide association study comprising 1464 patients and 12 019 controls of Northwestern European ancestry, with replication in an independent sample set of 1575 patients and 1367 controls. RESULTS The variant rs2412971, intronic in HORMAD2 at chromosome 22q12.2, was robustly associated with tonsillectomy (OR=1.22; p=1.48×10-9) and is highly correlated with SNPs previously found to be associated with IgA nephropathy, Crohn's disease (CD) and early onset inflammatory bowel disease (IBD). The risk allele for tonsillectomy corresponded to increased risk of IgA nephropathy and decreased risk of CD and IBD. We further performed lookup analyses of the top SNP for outcomes related to tonsillectomy in the combined discovery and replication sample and found that rs2412971 was associated with acute tonsillitis (OR=1.19; p=7.82×10-4), chronic disease of the tonsils (OR=1.19; p=2.32×10-6) and appendectomy (OR=1.18; p=1.13×10-3). CONCLUSIONS We identified and replicated a genetic association at 22q12.2 with tonsillectomy. Further functional investigation is required to illuminate whether the molecular mechanisms underlying the genetic association involve general lymphoid hyper-reaction throughout the mucosa-associated lymphoid tissue system.
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Affiliation(s)
- Bjarke Feenstra
- Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark
| | - Peter Bager
- Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark
| | - Xueping Liu
- Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark
| | - Henrik Hjalgrim
- Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.,Department of Haematology, Rigshospitalet, Copenhagen, Denmark
| | - Ellen A Nohr
- Research Unit of Gynaecology & Obstetrics, Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - David M Hougaard
- Danish Centre for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark
| | - Frank Geller
- Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark
| | - Mads Melbye
- Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.,Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.,Department of Medicine, Stanford University School of Medicine, Stanford, California, USA
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19
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Sun W, Han X, Wu S, Yang C. Tonsillectomy and the risk of inflammatory bowel disease: A systematic review and meta-analysis. J Gastroenterol Hepatol 2016; 31:1085-94. [PMID: 26678358 DOI: 10.1111/jgh.13273] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2015] [Revised: 10/19/2015] [Accepted: 12/06/2015] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIM Tonsillectomy remains a controversial environmental factor in the etiology of inflammatory bowel disease (IBD). This meta-analysis aims to elucidate a more defined role of tonsillectomy in the development of IBD. METHODS Four databases, including PubMed, EMBASE, the Cochrane Library, and Web of Science, were searched for studies exploring the association between tonsillectomy and the risk of IBD. The pooled estimates of odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random effects model. Heterogeneity was assessed using chi-squared and I(2) statistical analysis. A funnel plot was performed to assess publication bias. RESULTS A total of 23 observational studies involving 19 569 patients were included in our meta-analysis. Of these, 17 studies investigated the association between tonsillectomy and Crohn's disease (CD), and 22 studies explored its relationship with ulcerative colitis (UC). Overall, a positive relationship between tonsillectomy and development of CD (OR 1.37, 95% CI: 1.16-1.62) was observed, while there was no association between tonsillectomy and UC (OR 0.94, 95% CI: 0.84-1.05). When ORs were adjusted for smoking, the pooled OR for CD increased to 1.66 (95% CI: 1.03-2.68) and, for UC, changed to 1.03 (95% CI: 0.74-1.44). CONCLUSIONS This meta-analysis demonstrates that tonsillectomy is associated with an increased risk of developing CD. We found no evidence to suggest that tonsillectomy exerts a protective effect on the development of UC, as is the case with appendectomy. Further prospective studies are required to confirm the validity of these observations.
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Affiliation(s)
- Weili Sun
- Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China
| | - Xiao Han
- Department of Gastroenterology, the First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Siyuan Wu
- Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China
| | - Chuanhua Yang
- Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China
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20
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Xiong HF, Wang B, Zhao ZH, Hong J, Zhu Y, Zhou X, Xie Y. Tonsillectomy and inflammatory bowel disease: a meta-analysis. Colorectal Dis 2016; 18:O145-53. [PMID: 26946482 DOI: 10.1111/codi.13323] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2015] [Accepted: 11/24/2015] [Indexed: 12/14/2022]
Abstract
AIM The pathogenesis of inflammatory bowel diseases remains unclear. Genetic and environmental factors are involved. Studies of the association between tonsillectomy and inflammatory bowel disease have yielded conflicting results. METHOD PubMed and EMBASE were searched to identify studies evaluating the association between tonsillectomy and inflammatory bowel disease [Crohn's disease (CD) and ulcerative colitis (UC)]. Odds ratios with 95% CI were calculated using a random- or fixed-effects model. The χ(2) test and I(2) test were used to assess homogeneity. Egger's test was used to evaluate publication bias. RESULTS Thirteen observational case-control studies including 4122 patients (3035 UC/1087 CD) and 5103 controls were analysed. The summary odds ratio estimated for UC following a tonsillectomy was 0.932, 95% CI 0.819-1.062. The odds ratio for CD following a tonsillectomy was 1.194, 95% CI 0.992-1.437. Publication bias was not detected (Egger's test coefficient -3.50 to 1.55; P = 0.39). CONCLUSION No obvious association between tonsillectomy and inflammatory bowel disease was identified in our meta-analysis.
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Affiliation(s)
- H-F Xiong
- Department of Gastroenterology, First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi Province, China
| | - B Wang
- Department of Gastroenterology, First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi Province, China
| | - Z-H Zhao
- First School of Clinical Medicine, Lanzhou University, Lanzhou, Gansu Province, China
| | - J Hong
- Department of Gastroenterology, First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi Province, China
| | - Y Zhu
- Department of Gastroenterology, First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi Province, China
| | - X Zhou
- Department of Gastroenterology, First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi Province, China
| | - Y Xie
- Department of Gastroenterology, First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi Province, China
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21
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Legaki E, Gazouli M. Influence of environmental factors in the development of inflammatory bowel diseases. World J Gastrointest Pharmacol Ther 2016; 7:112-125. [PMID: 26855817 PMCID: PMC4734944 DOI: 10.4292/wjgpt.v7.i1.112] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2015] [Revised: 10/20/2015] [Accepted: 12/03/2015] [Indexed: 02/06/2023] Open
Abstract
Idiopathic inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC), are multifactorial diseases that are manifested after disruption of a genetic predisposed individual and its intestinal microflora through an environmental stimulus. Urbanization and industrialization are associated with IBD. Epidemiological data, clinical observations and family/immigrants studies indicate the significance of environmental influence in the development of IBD. Some environmental factors have a different effect on the subtypes of IBD. Smoking and appendectomy is negatively associated with UC, but they are aggravating factors for CD. A westernized high fat diet, full of refined carbohydrates is strongly associated with the development of IBD, contrary to a high in fruit, vegetables and polyunsaturated fatty acid-3 diet that is protective against these diseases. High intake of nonsteroidal antiinflammatory drug and oral contraceptive pills as well as the inadequacy of vitamin D leads to an increased risk for IBD and a more malignant course of disease. Moreover, other factors such as air pollution, psychological factors, sleep disturbances and exercise influence the development and the course of IBD. Epigenetic mechanism like DNA methylation, histone modification and altered expression of miRNAS could explain the connection between genes and environmental factors in triggering the development of IBD.
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22
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The Link between the Appendix and Ulcerative Colitis: Clinical Relevance and Potential Immunological Mechanisms. Am J Gastroenterol 2016; 111:163-9. [PMID: 26416189 DOI: 10.1038/ajg.2015.301] [Citation(s) in RCA: 71] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2015] [Accepted: 08/11/2015] [Indexed: 12/11/2022]
Abstract
The human appendix has long been considered as a vestigial organ, an organ that has lost its function during evolution. In recent years, however, reports have emerged that link the appendix to numerous immunological functions in humans. Evidence has been presented for an important role of the appendix in maintaining intestinal health. This theory suggests that the appendix may be a reservoir or 'safe house' from which the commensal gut flora can rapidly be reestablished if it is eradicated from the colon. However, the appendix may also have a role in the development of inflammatory bowel disease (IBD). Several large epidemiological cohort studies have demonstrated the preventive effect of appendectomy on the development of ulcerative colitis, a finding that has been confirmed in murine colitis models. In addition, current studies are examining the possible therapeutic effect of an appendectomy to modulate disease course in patients with ulcerative colitis. This literature review assesses the current knowledge about the clinical and immunological aspects of the vermiform appendix in IBD and suggests that the idea of the appendix as a vestigial remnant should be discarded.
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23
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Ye Y, Pang Z, Chen W, Ju S, Zhou C. The epidemiology and risk factors of inflammatory bowel disease. Int J Clin Exp Med 2015; 8:22529-22542. [PMID: 26885239 PMCID: PMC4730025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2015] [Accepted: 11/23/2015] [Indexed: 06/05/2023]
Abstract
This review aimed to summarize the epidemiology (incidence, prevalence and morality) and risk factors of inflammatory bowel disease (IBD). IBD is a chronic, relapsing, inflammatory disorder of the gastrointestinal tract and includes Crohn's Disease (CD) and ulcerative colitis (UC). IBD has increasing incidence and prevalence in most of countries and becomes a global emerging disease. A westernized lifestyle or habits and some environmental factors have been found to contribute to the pathogenesis of IBD. The relevant risk factors include Smoking, hygiene hypothesis, microorganisms, appendectomy, medication, nutrition, and stress have all been found to be associated with the modality of IBD, but results are inconsistent on this issue in available studies. Therefore, more studies are required to identify and understand the environmental determinants of IBD.
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Affiliation(s)
- Yulan Ye
- Department of Gastroenterology, The Affiliated Suzhou Hospital of Nanjing Medical UniversitySuzhou 215006, Jiangsu, China
| | - Zhi Pang
- Department of Gastroenterology, The Affiliated Suzhou Hospital of Nanjing Medical UniversitySuzhou 215006, Jiangsu, China
| | - Weichang Chen
- Department of Gastroenterology, The First Affiliated Hospital of College of Medicine, Soochow UniversitySuzhou 215000, Jiangsu, China
| | - Songwen Ju
- Department of Gastroenterology, The Affiliated Suzhou Hospital of Nanjing Medical UniversitySuzhou 215006, Jiangsu, China
| | - Chunli Zhou
- Department of Gastroenterology, The Affiliated Suzhou Hospital of Nanjing Medical UniversitySuzhou 215006, Jiangsu, China
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Andreu-Ballester JC, Gil-Borrás R, García-Ballesteros C, Catalán-Serra I, Amigo V, Fernández-Fígares V, Cuéllar C. Epstein-Barr virus is related with 5-aminosalicylic acid, tonsillectomy, and CD19 + cells in Crohn’s disease. World J Gastroenterol 2015; 21:4666-4672. [PMID: 25914477 PMCID: PMC4402315 DOI: 10.3748/wjg.v21.i15.4666] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2014] [Revised: 07/24/2014] [Accepted: 10/15/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To study anti-Epstein-Barr virus (EBV) IgG antibodies in Crohn´s disease in relation to treatment, immune cells, and prior tonsillectomy/appendectomy.
METHODS: This study included 36 CD patients and 36 healthy individuals (controls), and evaluated different clinical scenarios (new patient, remission and active disease), previous mucosa-associated lymphoid tissue removal (tonsillectomy and appendectomy) and therapeutic regimens (5-aminosalicylic acid, azathioprine, anti-tumor necrosis factor, antibiotics, and corticosteroids). T and B cells subsets in peripheral blood were analyzed by flow cytometry (markers included: CD45, CD4, CD8, CD3, CD19, CD56, CD2, CD3, TCRαβ and TCRγδ) to relate with the levels of anti-EBV IgG antibodies, determined by enzyme-linked immunosorbent assay.
RESULTS: The lowest anti-EBV IgG levels were observed in the group of patients that were not in a specific treatment (95.4 ± 53.9 U/mL vs 131.5 ± 46.2 U/mL, P = 0.038). The patients that were treated with 5-aminosalicylic acid showed the highest anti-EBV IgG values (144.3 U/mL vs 102.6 U/mL, P = 0.045). CD19+ cells had the largest decrease in the group of CD patients that received treatment (138.6 vs 223.9, P = 0.022). The analysis of anti-EBV IgG with respect to the presence or absence of tonsillectomy showed the highest values in the tonsillectomy group of CD patients (169.2 ± 20.7 U/mL vs 106.1 ± 50.3 U/mL, P = 0.002). However, in the group of healthy controls, no differences were seen between those who had been tonsillectomized and subjects who had not been operated on (134.0 ± 52.5 U/mL vs 127.7 ± 48.1 U/mL, P = 0.523).
CONCLUSION: High anti-EBV IgG levels in CD are associated with 5-aminosalicylic acid treatment, tonsillectomy, and decrease of CD19+ cells.
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Environment and the inflammatory bowel diseases. CANADIAN JOURNAL OF GASTROENTEROLOGY = JOURNAL CANADIEN DE GASTROENTEROLOGIE 2015; 27:e18-24. [PMID: 23516681 DOI: 10.1155/2013/102859] [Citation(s) in RCA: 104] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Inflammatory bowel diseases (IBD), which consists of Crohn disease and ulcerative colitis, are chronic inflammatory conditions of the gastrointestinal tract. In genetically susceptible individuals, the interaction between environmental factors and normal intestinal commensal flora is believed to lead to an inappropriate immune response that results in chronic inflammation. The incidence of IBD have increased in the past century in developed and developing countries. The purpose of the present review is to summarize the current knowledge of the association between environmental risk factors and IBD. A number of environmental risk factors were investigated including smoking, hygiene, microorganisms, oral contraceptives, antibiotics, diet, breastfeeding, geographical factors, pollution and stress. Inconsistent findings among the studies highlight the complex pathogenesis of IBD. Additional studies are necessary to identify and elucidate the role of environmental factors in IBD etiology.
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Recurrent IgA nephropathy complicated with Crohn's disease after renal transplantation. CEN Case Rep 2014; 3:167-171. [PMID: 28509194 DOI: 10.1007/s13730-014-0111-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2013] [Accepted: 01/28/2014] [Indexed: 10/25/2022] Open
Abstract
A 27-year-old man was diagnosed with IgA nephropathy and Crohn's disease. He had been diagnosed with proteinuria and hematuria since he was 20 years old. Diarrhea had been a continuing problem during the past 5 months. Neither corticosteroid therapy nor tonsillectomy was performed. Hemodialysis was required at age of 30, while the symptoms of Crohn's disease were ameliorated by an elemental diet. He received a renal transplant from his mother 4 months after starting dialysis therapy. The initial immunosuppression therapy consisted of methylprednisolone, mycofenolate mofetil, cyclosporine, and basiliximab. Eight months after transplantation, proteinuria and hematuria appeared and serum creatinine was 1.4 mg/dL. Relapse of IgA nephropathy was confirmed by the one-year protocol biopsy. He had suffered from tonsillitis at 32 months after the transplantation. Urinary protein increased to 3 g/day and serum creatinine was elevated to 2.04 mg/dL. Renal biopsy was performed 2 weeks after the urinary findings were aggravated. The cellular crescents constituted 36 % of the glomeruli. The findings of rejection were not confirmed in both biopsies. Tonsillectomy was performed thereafter. No additional immunosuppressive therapy was added. Proteinuria and hematuria disappeared at 4 and 20 months, respectively, after tonsillectomy, even when the symptoms of Crohn's disease worsened 69 months and 89 months after transplantation. A renal biopsy was performed 101 months after transplantation. Although IgA in the mesangium area was confirmed by immunohistochemical staining, no active lesion was seen. Tonsillectomy along with immunosuppressants for the graft might be an effective treatment for some patients with active recurrent IgA nephropathy.
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Experimental appendicitis and appendectomy modulate the CCL20-CCR6 axis to limit inflammatory colitis pathology. Int J Colorectal Dis 2014; 29:1181-8. [PMID: 24980688 DOI: 10.1007/s00384-014-1936-5] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/12/2014] [Indexed: 02/04/2023]
Abstract
BACKGROUND Crohn's disease and ulcerative colitis are the two spectral variations of inflammatory bowel diseases (IBD). The complex interplay between genetic predisposition, gastrointestinal bacteria, and gut immunity in IBD is yet to be deciphered. The newly described IL-17-secreting subset of CD4+ T cells, called Th17 cells (and its "Th17 system"), has been increasingly implicated in the pathogenesis of inflammatory changes in inflammatory/autoimmune diseases including IBD. The chemokine ligand CCL20 and its receptor CCR6 are both upregulated in colon biopsy samples during active IBD. Appendicitis and appendectomy (AA) prevents or significantly ameliorates human IBD. METHODS We pioneered the first animal model of AA. AA was performed on 5-week-old male BALB/c mice, and distal-colon samples were harvested. Mice with two laparotomies each served as sham and sham (SS) controls. RNA was extracted from individual colonic replicate samples (AA and SS groups) and each sample microarray analyzed and reverse transcription-polymerase chain reaction (RT-PCR) validated. Gene set enrichment analysis (GSEA) software was used to further analyze the microarray data. RESULTS Prior AA ameliorates experimental colitis in our murine model. CCL20 expression was significantly suppressed (along with components of the Th17 system) in the most distal colon 3 and 28 days after AA was done at the most proximal colon. CONCLUSION Teasing out the pathways involved in the changes induced by AA on the colon in clinical studies and, most importantly, in our unique murine AA model will lead to the development of techniques to manipulate different components of the CCL20-CCR6 axis and Th17 system resulting in significant advances in IBD management.
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Cheluvappa R. A novel model of appendicitis and appendectomy to investigate inflammatory bowel disease pathogenesis and remediation. Biol Proced Online 2014; 16:10. [PMID: 24999306 PMCID: PMC4082674 DOI: 10.1186/1480-9222-16-10] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2014] [Accepted: 06/09/2014] [Indexed: 01/07/2023] Open
Abstract
The appendix contains copious lymphoid tissue and is constantly exposed to gut flora. Appendicitis and appendectomy (AA) has been shown to prevent or significantly ameliorate ulcerative colitis. In our novel murine AA model, the only existing experimental model of AA, the appendiceal pathology closely resembles that of human appendicitis; and AA offers an age-, bacteria- and antigen-dependent protection against colitis. Appendicitis and appendectomy performed in the most proximal colon curbs T helper 17 cell activity, curtails autophagy, modulates interferon activity-associated molecules, and suppresses endothelin vasoactivity-mediated immunopathology/vascular remodelling in the most distal colon. These AA-induced changes contribute to the limitation/amelioration of colitis pathology. Investigating strategies to manipulate and modulate different aspects of these pathways (using monoclonal antibodies, combinatorial peptides, and small molecules) would offer novel insight into inflammatory bowel disease pathogenesis, and will augment the development of new therapeutic options to manage recalcitrant colitis.
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Affiliation(s)
- Rajkumar Cheluvappa
- Department of Medicine, St George Clinical School, University of New South Wales, Sydney, NSW, Australia ; Inflammation and Infection Research Centre, School of Medical Sciences, Wallace Wurth Building, University of New South Wales, Gate 9 High Street, Sydney, NSW 2052, Australia
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Abstract
BACKGROUND When done at a young age, appendicitis followed by appendectomy (AA) offers protection against ulcerative colitis development in later life. We developed the first ever murine AA model. Using this model, we showed earlier that previous AA ameliorated colitis. We aimed to determine whether autophagy genes contribute to the anti-colitis protection conferred by AA, and if so, to delineate the autophagy-linked genes involved in this. METHODS Mice with 2 laparotomies each served as controls (sham-sham). Distal colons were harvested (4 AA-group colons, 4 sham-sham group colons), and RNA extracted from each. The RNA was taken through microarray analysis or reverse transcription-polymerase chain reaction validation. Gene set enrichment analysis software was used to analyze the microarray data. RESULTS Out of 28 key autophagy-related genes investigated (VPS15, VPS34, FIP200, ATG03, ATG04A, ATG04B, ATG05, ATG07, ATG10, ATG12, ATG13b, ATG14, ATG16L1, BECN1, GABARAPL1, IRGM1, IRGM2, LAMP2, LC3A, LC3B, RAB7A, UVRAG, NOD2, XBP1, LRRK2, ULK1, ULK2, PTPN2), 7 have genetic associations with inflammatory bowel diseases (ATG16L1, IRGM1, NOD2, XBP1, LRRK2, ULK1, PTPN2). There was slight upregulation of IRGM1, FIP200, and ATG04A (P < 0.05), but no variations with the other 25 genes. In contrast, gene set enrichment analysis revealed that AA downregulated 74 gene sets (associated with 28 autophagy genes) while upregulating only 5 (false discovery rate <5%; P < 0.001) gene sets. Additionally, 22 gene sets associated with the 7 autophagy + inflammatory bowel disease-associated genes were downregulated by AA, whereas only 3 were upregulated. The genes with maximum AA-induced gene set suppression were VPS15, LAMP2, LC3A, XBP1, and ULK1. CONCLUSIONS AA induces profound autophagy suppression in the distal colon. The AA-induced upregulation of individual genes (IRGM1, FIP200, ATG04A) could be a reflection of complex compensatory changes or the initial abnormality that led to the pronounced autophagy suppression. Autophagy suppression by AA may induce lesser antigen processing, leading to lesser cross-reactive immunity between microbes and self-antigens, and subsequent amelioration of colitis.
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Ko Y, Butcher R, Leong RW. Epidemiological studies of migration and environmental risk factors in the inflammatory bowel diseases. World J Gastroenterol 2014; 20:1238-47. [PMID: 24574798 PMCID: PMC3921506 DOI: 10.3748/wjg.v20.i5.1238] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2013] [Revised: 11/27/2013] [Accepted: 01/02/2014] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel diseases (IBD) are idiopathic chronic diseases of the gastrointestinal tract well known to be associated with both genetic and environmental risk factors. Permissive genotypes may manifest into clinical phenotypes under certain environmental influences and these may be best studied from migratory studies. Exploring differences between first and second generation migrants may further highlight the contribution of environmental factors towards the development of IBD. There are few opportunities that have been offered so far. We aim to review the available migration studies on IBD, evaluate the known environmental factors associated with IBD, and explore modern migration patterns to identify new opportunities and candidate migrant groups in IBD migration research.
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The role of the environment in the development of pediatric inflammatory bowel disease. Curr Gastroenterol Rep 2013; 15:326. [PMID: 23640032 DOI: 10.1007/s11894-013-0326-4] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
The incidence of inflammatory bowel disease (IBD) is rising worldwide, with a particularly sharp increase in children. Rates are highest in North America and Europe, with rapid increases noted in developing nations adopting the Westernized environment. While many genetic risk loci have been identified that predispose people to IBD, incomplete penetrance and overlapping genotypes among patients with different phenotypes inadequately explain the etiology of these chronic diseases. Therefore, environmental risk factors have been the subject of much recent research. This article reviews the role of the environment in IBD, with particular focus on early-life exposures and pediatric-onset disease. The literature surrounding environmental risk factors is reviewed, including prenatal and perinatal exposures, the hygiene hypothesis, the urban environment, infection and antibiotic use, and secondhand tobacco smoke exposure. In addition, the possible role of the environment in altering the intestinal microbiome is addressed.
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Pre-colectomy appendectomy and risk for Crohn's disease in patients with ileal pouch-anal anastomosis. J Gastrointest Surg 2012; 16:1370-8. [PMID: 22528574 DOI: 10.1007/s11605-012-1889-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2011] [Accepted: 04/10/2012] [Indexed: 02/07/2023]
Abstract
BACKGROUND A subset of patients with a pre-operative diagnosis of ulcerative colitis can develop Crohn's disease (CD) of the pouch after restorative proctocolectomy. While appendectomy has been implicated to be associated with an increased risk for CD, its impact on the development of de novo CD of the pouch in patients' ileal pouch-anal anastomosis (IPAA) has not been studied. The aims of the study were to assess the prevalence of CD of the pouch in patients with pre-colectomy appendectomy and to investigate the impact of appendectomy on the development of de novo CD of the pouch. METHODS All eligible patients with restorative proctocolectomy and IPAA for IBD who had available information on pre-colectomy appendectomy were studied. Demographic and clinical characteristics were evaluated. Cox regression analysis was performed. RESULTS The study included 434 patients (44.9 % male) with a mean age of 45.2 ± 4.4 years and follow-up of 4.6 ± 2.3 years. Forty patients (9.2 %) had had appendectomy prior to colectomy. Appendectomy was not shown to be associated with CD of the pouch or its phenotypes in both univariable and multivariable analyses. In the Cox model, independent risk factors associated with CD of the pouch were active smoking (hazard ratio [HR] =1.58; 95 % confidence interval [CI], 1.03-2.43) and family history of CD (HR=1.82; 95 % CI, 0.99-3.32). CONCLUSIONS While this study has shown no association between previous appendectomy and the development of CD of pouch, active smoking was an independent risk factor for development of CD of the pouch.
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Spehlmann ME, Begun AZ, Saroglou E, Hinrichs F, Tiemann U, Raedler A, Schreiber S. Risk factors in German twins with inflammatory bowel disease: results of a questionnaire-based survey. J Crohns Colitis 2012; 6:29-42. [PMID: 22261525 DOI: 10.1016/j.crohns.2011.06.007] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2011] [Revised: 06/16/2011] [Accepted: 06/16/2011] [Indexed: 12/12/2022]
Abstract
INTRODUCTION Environmental factors may play an important role in the pathogenesis of IBD. The history of patients of the German IBD twin study was analyzed by questionnaires and interviews. METHODS Randomly selected German monozygotic (MZ) and dizygotic (DZ) twins with at least one sibling suffering from IBD (n=512) were characterized in detail including demography, medical history and concomitant medications. Controls comprised of non-twin IBD patients (n=392) and healthy subjects (n=207). RESULTS The most significant variables that were associated with Crohn's disease (CD) or ulcerative colitis (UC) included living abroad before time of diagnosis (OR, 4.32; 95% CI, 1.57-13.69), high frequency of antibiotic use (MZ CD OR, 5.03; 95% CI 1.61-17.74, DZ CD OR, 7.66; 95% CI, 3.63-16.82, MZ UC OR, 3.82; 95% CI, 1.45-10.56, DZ UC OR, 3.08; CI, 1.63-5.92), high consumption of processed meat including sausage (MZ CD OR, 7.9; 95% CI, 2.15-38.12, DZ CD OR, 10.75; 95% CI, 4.82-25.55, MZ UC OR, 5.69; 95% CI, 1.89-19.48, DZ UC OR, 18.11; 95% CI, 7.34-50.85), and recall of bacterial gastrointestinal infections (MZ CD OR, 15.9; 95% CI, 4.33-77.14, DZ CD OR, 17.21; 95% CI, 4.47-112.5, MZ UC OR, 5.87; 95% CI, 1.61-28.0, DZ UC OR, 11.34; 95% CI, 4.81-29.67). CONCLUSIONS This study reinforced the association of life style events, in particular a specific dietary and infections history, with IBD. Alteration of gut flora or alterations of the mucosal immune system in reactivity to the flora could be an important factor to explain the relationship between life-style and disease.
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Affiliation(s)
- Martina E Spehlmann
- Clinic of General Internal Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Schittenhelmstrasse 12, 24105 Kiel, Germany.
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Hansen TS, Jess T, Vind I, Elkjaer M, Nielsen MF, Gamborg M, Munkholm P. Environmental factors in inflammatory bowel disease: a case-control study based on a Danish inception cohort. J Crohns Colitis 2011; 5:577-84. [PMID: 22115378 DOI: 10.1016/j.crohns.2011.05.010] [Citation(s) in RCA: 125] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2010] [Revised: 05/19/2011] [Accepted: 05/26/2011] [Indexed: 02/08/2023]
Abstract
BACKGROUND The role of environmental factors in development of inflammatory bowel disease (IBD) remains uncertain. The aim of the present study was to assess a number of formerly suggested environmental factors in a case-control study of an unselected and recently diagnosed group of patients with IBD and a control group of orthopaedic patients. METHODS A total of 123 patients diagnosed with Crohn's disease (CD) and 144 with ulcerative colitis (UC) in Copenhagen (2003-2004) were matched 1:1 on age and gender to 267 orthopaedic controls. Participants received a questionnaire with 87 questions concerning environmental factors prior to IBD/orthopaedic admission. Odds ratios (OR) were calculated by logistic regression. RESULTS Being breastfed >6 months (OR, 0.50; 95% CI, 0.23-1.11) and undergoing tonsillectomy (OR, 0.49; 95% CI, 0.31-0.78) decreased the odds for IBD, whereas appendectomy decreased the odds for UC only (OR, 0.29; 95% CI, 0.12-0.71). Vaccination against pertussis (OR, 2.08; 95% CI, 1.07-4.03) and polio (OR, 2.38; 95% CI, 1.04-5.43) increased the odds for IBD, whereas measles infection increased the odds for UC (OR, 3.50; 95% CI, 1.15-10.6). Low consumption of fibres and high consumption of sugar were significantly associated with development of CD and UC. Smoking increased the risk for CD and protected against UC. CONCLUSION Among Danish patients with CD and UC belonging to an unselected cohort, disease occurrence was found to be associated both with well-known factors such as smoking and appendectomy, and with more debated factors including breastfeeding, tonsillectomy, childhood vaccinations, childhood infections, and dietary intake of fibres and sugar.
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Affiliation(s)
- Tanja Stenbaek Hansen
- Gastrointestinal Unit, Medical Section, Herlev University Hospital, Statens Serum Institut, Copenhagen, Denmark
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Jutte DP, Roos LL, Brownell MD. Administrative record linkage as a tool for public health research. Annu Rev Public Health 2011; 32:91-108. [PMID: 21219160 DOI: 10.1146/annurev-publhealth-031210-100700] [Citation(s) in RCA: 236] [Impact Index Per Article: 16.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Linked administrative databases offer a powerful resource for studying important public health issues. Methods developed and implemented in several jurisdictions across the globe have achieved high-quality linkages for conducting health and social research without compromising confidentiality. Key data available for linkage include health services utilization, population registries, place of residence, family ties, educational outcomes, and use of social services. Linking events for large populations of individuals across disparate sources and over time permits a range of research possibilities, including the capacity to study low-prevalence exposure-disease associations, multiple outcome domains within the same cohort of individuals, service utilization and chronic disease patterns, and life course and transgenerational transmission of health. Limited information on variables such as individual-level socioeconomic status (SES) and social supports is outweighed by strengths that include comprehensive follow-up, continuous data collection, objective measures, and relatively low expense. Ever advancing methodologies and data holdings guarantee that research using linked administrative databases will make increasingly important contributions to public health research.
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Affiliation(s)
- Douglas P Jutte
- School of Public Health, University of California, Berkeley, 94720-1190, USA.
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Molodecky NA, Kaplan GG. Environmental risk factors for inflammatory bowel disease. Gastroenterol Hepatol (N Y) 2010; 6:339-346. [PMID: 20567592 PMCID: PMC2886488] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/29/2023]
Abstract
Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract and is associated with significant morbidity. The etiology of IBD has been extensively studied during the last several decades; however, causative factors in disease pathology are not yet fully understood. IBD is thought to result from the interaction between genetic and environmental factors that influence the normal intestinal commensal flora to trigger an inappropriate mucosal immune response. Although many IBD susceptibility genes have been discovered, similar advances in defining environmental risk factors have lagged. A number of environmental risk factors have been explored, including smoking, appendectomy, oral contraceptives, diet, breastfeeding, infections/ vaccinations, antibiotics, and childhood hygiene. However, most of these factors have demonstrated inconsistent findings, thus making additional studies necessary to better understand the etiology of IBD.
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Singhal R, Taylor J, Owoniyi M, El-Khayat RH, Tyagi SK, Corfield AP. The role of appendicectomy in the subsequent development of inflammatory bowel disease: a UK-based study. Int J Colorectal Dis 2010; 25:509-13. [PMID: 20012972 DOI: 10.1007/s00384-009-0865-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/24/2009] [Indexed: 02/04/2023]
Abstract
BACKGROUND Several studies have shown an inverse relationship between appendicectomy and subsequent development of inflammatory bowel disease (IBD), although these findings remain contentious. This study aims to further elucidate the role appendicitis/appendicectomy has in the development of IBD. METHOD All patients undergoing appendicectomy at Hereford County Hospital between 1986 and 2005 were identified from pathology records. Those already diagnosed with IBD were excluded. Age- and sex-matched controls were randomly selected from a database of orthopaedic clinic attendees. Those with prior history of IBD or appendicectomy were excluded. The incidence of IBD was determined by cross-referencing with the histology database, colonoscopy database and IBD register. RESULTS Three thousand eight hundred twenty-nine patients were included in each group, with mean follow-up of 12 +/- 5.9 years. Twelve patients in the appendicectomy group developed IBD. Mean age at diagnosis was 30.3 years, and mean interval from appendicectomy of 3.7 years. Age at appendicectomy and appendicectomy for appendicitis conferred no benefit (Mann-Whitney test, p = 0.991). Eleven patients in the control group developed IBD, with no significant differences in any of the measured outcomes. CONCLUSION This study has shown no relationship between appendicitis/appendicectomy and development of IBD.
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Frisch M, Pedersen BV, Andersson RE. Appendicitis, mesenteric lymphadenitis, and subsequent risk of ulcerative colitis: cohort studies in Sweden and Denmark. BMJ 2009; 338:b716. [PMID: 19273506 PMCID: PMC2659291 DOI: 10.1136/bmj.b716] [Citation(s) in RCA: 60] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
OBJECTIVE To determine whether the repeatedly observed low risk of ulcerative colitis after appendicectomy is related to the appendicectomy itself or the underlying morbidity, notably appendicitis or mesenteric lymphadenitis. DESIGN Nationwide cohort studies. SETTING Sweden and Denmark. PARTICIPANTS 709 353 Swedish (1964-2004) and Danish (1977-2004) patients who had undergone appendicectomy were followed up for subsequent ulcerative colitis. The impact of appendicectomy on risk was also studied in 224 483 people whose parents or siblings had inflammatory bowel disease. MAIN OUTCOME MEASURES Standardised incidence ratios and rate ratios as measures of relative risk. RESULTS During 11.1 million years of follow-up in the appendicectomy cohort, 1192 patients developed ulcerative colitis (10.8 per 100 000 person years). Appendicectomy without underlying inflammation was not associated with reduced risk (standardised incidence ratio 1.04, 95% confidence interval 0.95 to 1.15). Before the age of 20, however, appendicectomy for appendicitis (0.45, 0.39 to 0.53) or mesenteric lymphadenitis (0.65, 0.46 to 0.90) was associated with significant risk reduction. A similar pattern was seen in those with affected relatives, whose overall risk of ulcerative colitis was clearly higher than the background risk (1404 observed v 446 expected; standardised incidence ratio 3.15, 2.99 to 3.32). In this cohort, appendicectomy without underlying appendicitis did not modify risk (rate ratio 1.04, 0.66 to 1.55, v no appendicectomy), while risk after appendicectomy for appendicitis was halved (0.49, 0.31 to 0.74). CONCLUSIONS In individuals with or without a familial predisposition to inflammatory bowel disease, appendicitis and mesenteric lymphadenitis during childhood or adolescence are linked to a significantly reduced risk of ulcerative colitis in adulthood. Appendicectomy itself does not protect against ulcerative colitis.
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Affiliation(s)
- Morten Frisch
- Department of Epidemiology Research, Division of Epidemiology, Statens Serum Institut, DK-2300 Copenhagen S, Denmark.
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Abstract
BACKGROUND It has been speculated that prenatal or perinatal exposure to infections affects the risk for developing inflammatory bowel disease (IBD). The aims of the study were to investigate the seasonal and monthly variations of birth dates among patients with Crohn's disease (CD) and ulcerative colitis (UC). METHODS The Hospital Episode Statistics (HES) comprises data of all patients admitted to hospitals in England. The data between April 1997 and March 2006 served to analyze birth dates of subjects with CD and UD, using the entirety of patients in the HES as controls. RESULTS Monthly birth dates were aggregated for the same months across consecutive birth years from January 1920 to December 1989 to determine whether a seasonal birth pattern existed among patients with CD and UC. No different seasonal birth patterns were observed between IBD patients and controls. A second analysis of individual months of birth, year after year, found that rates of births among IBD patients fluctuated from month to month. These fluctuations were different for CD and UC, with an overall weak correlation of r = 0.078, P = 0.018. There was a slight trend for stronger correlations to occur during more recent decades of birth, with r = 0.237 (P = 0.009) and r = 0.168 (P = 0.067) for the last 2 decades 1970-1979 and 1980-1989, respectively. CONCLUSIONS The patterns of birth dates among IBD patients do not support the contention that seasonally or monthly varying environmental factors during early childhood shape the subsequent risk of developing IBD.
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41
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Kaplan GG, Jackson T, Sands BE, Frisch M, Andersson RE, Korzenik J. The risk of developing Crohn's disease after an appendectomy: a meta-analysis. Am J Gastroenterol 2008; 103:2925-31. [PMID: 18775018 DOI: 10.1111/j.1572-0241.2008.02118.x] [Citation(s) in RCA: 89] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Studies exploring the association between appendectomy and Crohn's disease (CD) have reported conflicting findings. We conducted a systematic review of the literature and a meta-analysis to assess the risk of CD following an appendectomy and determine the effect of time between appendectomy and CD diagnosis. METHODS MEDLINE was used to identify observational studies evaluating the association between appendectomy and CD. Authors were contacted when data were insufficient. Relative risks (RR) with 95% confidence intervals (CI) were calculated using a random effects model. Studies that analyzed their data by the interval between the appendectomy and the diagnosis of CD were assessed separately. The Woolf chi(2) statistic was used to test for homogeneity. Egger's test was used to evaluate publication bias. RESULTS The summary RR estimate for CD following an appendectomy was significantly elevated (RR 1.61, 95% CI 1.28-2.02), though heterogeneity was observed (P < 0.0001). The risk was elevated within the first year following the operation (RR 6.69, 95% CI 5.42-8.25). The risk of CD was also significantly increased 1-4 yr following an appendectomy (RR 1.99, 95% CI 1.66- 2.38); however, after 5 yr or more, the risk fell to baseline levels (RR 1.08, 95% CI 0.99-1.18). Publication bias was not detected (P = 0.2). CONCLUSION The meta-analysis demonstrated a significant risk of CD following an appendectomy, though heterogeneity was observed between the studies. The elevated risk early after an appendectomy, which diminishes thereafter, likely reflects diagnostic problems in patients with incipient CD.
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Affiliation(s)
- Gilaad G Kaplan
- Inflammatory Bowel Disease Clinic, University of Calgary, Calgary, Alberta, Canada
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Oldmeadow C, Wood I, Mengersen K, Visscher PM, Martin NG, Duffy DL. Investigation of the relationship between smoking and appendicitis in Australian twins. Ann Epidemiol 2008; 18:631-6. [PMID: 18652981 DOI: 10.1016/j.annepidem.2008.04.004] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2008] [Revised: 04/02/2008] [Accepted: 04/06/2008] [Indexed: 12/14/2022]
Abstract
PURPOSE Appendicitis is an inflammation of the appendix, the etiology of which is still poorly understood. Previous studies have shown an increased risk for cigarette smokers but no accounts for the timing of exposure to smoking relative to appendectomy were made. METHODS Based on questionnaire data, both cohort and co-twin case-control analyses were conducted to assess the effect of active cigarette smoking on appendectomy in 3808 Australian twin pairs. Smoking status was defined as a time-dependent covariate to account for differences in timing of smoking initiation and onset of appendicitis. RESULTS The questionnaire had a 65% pairwise response rate. After controlling for sex, age, and year of birth, appendectomy risk in current smokers was statistically significantly increased by 65% relative to never-smokers. This was largely unchanged by the duration or intensity of smoking and was not affected by socioeconomic status or father's occupation. The effect was stronger in females. Among former smokers, increased time since quitting significantly reduced the odds ratio of appendectomy by 15% for every year since quitting. CONCLUSION After adjustment for age and other confounders, there was an increase in risk of appendectomy among current smokers relative to never-smokers, particularly in females. This study adds to the body of knowledge on the effects of tobacco smoking on the gastrointestinal tract.
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Affiliation(s)
- Chris Oldmeadow
- Department of Mathematical Sciences, Queensland University of Technology, Mathematical Sciences, O Block, Gardens Point Campus, Brisbane, Australia.
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43
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Abstract
BACKGROUND The time trends of inflammatory bowel disease are characterized by short-term variations that affect Crohn's disease and ulcerative colitis alike. The aim of the present study was to test whether these variations might be related to exacerbations of inflammatory bowel disease secondary to superimposed gastrointestinal infection. METHODS The Hospital Episode Statistics (HES) comprises a data set of all patients admitted to hospitals throughout England, which includes inpatients and day cases. This data set was used to analyze the monthly variations in all hospital admissions for Crohn's disease (ICD10 code K50), ulcerative colitis (K51), bacterial intestinal infections (A04), viral intestinal infections (A08), diarrhea and infectious gastroenteritis (A09), upper respiratory infections (J06), pneumonia secondary to unspecified organism (J18), and unspecified acute lower respiratory infection (J22). RESULTS The temporal analysis revealed similar monthly fluctuations of hospital admissions for Crohn's disease, ulcerative colitis, and bacterial intestinal infections. Viral intestinal infections and infectious gastroenteritis were characterized by different seasonal variations that showed no relationship with any of the fluctuations of inflammatory bowel disease or bacterial intestinal infections. Similarly, respiratory infections resulted in marked cyclical variations in hospital admissions unrelated to any changes in inflammatory bowel disease or enteric infections. CONCLUSIONS The similarity in the time trends of Crohn's disease, ulcerative colitis, and bacterial intestinal infections suggests that superinfection by intestinal bacteria are responsible for the fluctuations in hospital admissions for inflammatory bowel disease.
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Affiliation(s)
- Amnon Sonnenberg
- Portland VA Medical Center-P3-GI, 3710 SW US Veterans Hospital Road, Portland, OR 97239, USA.
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44
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Kaplan GG, Pedersen BV, Andersson RE, Sands BE, Korzenik J, Frisch M. The risk of developing Crohn's disease after an appendectomy: a population-based cohort study in Sweden and Denmark. Gut 2007; 56:1387-92. [PMID: 17494106 PMCID: PMC2000241 DOI: 10.1136/gut.2007.121467] [Citation(s) in RCA: 59] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND The relationship between appendectomy and Crohn's disease is controversial. A Swedish-Danish cohort study was conducted to assess the risk of developing Crohn's disease after an appendectomy. METHODS 709 353 appendectomy patients in Sweden (since 1964) and Denmark (since 1977) were followed for first hospitalisations for Crohn's disease to 2004. Standardised incidence ratios (SIR) served as relative risks. RESULTS Overall, 1655 Crohn's disease cases were observed during 11.1 million person-years of follow-up. Whereas appendectomy before the age of 10 years was not associated with the risk of Crohn's disease (SIR 1.00; 95% CI 0.80-1.25), the overall SIR of developing Crohn's disease was 1.52 (95% CI 1.45-1.59), being highest in the first 6 months (SIR 8.69; 95% CI 7.68-9.84). SIR diminished rapidly thereafter, with the risk of Crohn's disease reaching background levels after 5-10 years for Crohn's disease overall, as well as for Crohn's ileitis, ileocolonic Crohn's disease, Crohn's colitis and other/unspecified Crohn's disease. A long-term increased risk of Crohn's disease up to 20 years after the appendectomy was seen only in appendectomy patients without appendicitis or mesenteric lymphadenitis. CONCLUSION The transient increased risk of Crohn's disease after an appendectomy is probably explained by diagnostic bias.
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45
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Zabana Y, Domènech E, Latorre N, Ojanguren I, Mañosa M, Gassull MA. [Acute appendicitis in inactive extensive ulcerative colitis]. GASTROENTEROLOGIA Y HEPATOLOGIA 2007; 30:69-73. [PMID: 17335713 DOI: 10.1157/13099267] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Appendectomy is associated with a reduced risk of developing ulcerative colitis (UC). In addition, there may be appendicular involvement in UC in patients with extensive or even left-sided disease. However, no data are available on the incidence, clinical presentation and outcome of acute appendicitis in patients previously diagnosed with UC. The impact of appendectomy in this subset of patients also remains to be determined. We describe 2 cases of acute appendicitis in the setting of inactive extensive ulcerative colitis and compare their histologic features with those of the surgical specimens of 2 further UC patients colectomized for refractory and extensive disease.
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Affiliation(s)
- Yamile Zabana
- Servicio de Aparato Digestivo, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain
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46
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Firouzi F, Bahari A, Aghazadeh R, Zali MR. Appendectomy, tonsillectomy, and risk of inflammatory bowel disease: a case control study in Iran. Int J Colorectal Dis 2006; 21:155-9. [PMID: 15937693 DOI: 10.1007/s00384-005-0760-3] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/18/2005] [Indexed: 02/04/2023]
Abstract
There is some controversy about the prevalence of appendectomy and tonsillectomy among patients with Crohn's disease and a lower rate of appendectomy among patients with ulcerative colitis (UC). The objective of this study was to elucidate the role of appendectomy and tonsillectomy in Iranian patients with inflammatory bowel disease (IBD). Three hundred and eighty-two consecutive cases of UC and 46 cases of CD were included. Age and sex-matched controls were randomly selected. A total of 382 controls for UC and 184 controls for CD were enrolled. A standard record concerning smoking habit, history of appendectomy and tonsillectomy, OCP, and NSAID use was completed. Logistic regression analysis was used to evaluate potential confounding variables. Twelve patients (3.1%) with UC reported a previous history of appendectomy compared with 30 controls (7.9%) (OR=0.38, 95%CI=0.19-0.76, P<0.004). Appendectomy was reported by five patients (10.9%) with CD compared with four controls (2.2%) (OR=5.49, 95%CI=1.41-21.34, P<0.02). The logistic regression analysis showed that appendectomy is a risk factor in CD but has a modest protective effect for development of UC. No association with tonsillectomy was found for either disease. A statistically significant protective effect for smoking in UC was found (OR=0.2, 95%CI=0.13-0.32, P<0.0001). We have found an inverse association between OCP and NSAID use with UC, but not CD (P<0.0001 and P<0.001, respectively). Appendectomy is protective in UC, but a risk factor in CD among Iranian population. Tonsillectomy was not associated with either UC or CD disease. UC, but not CD, is a disease of non-smokers. The inverse association between ulcerative colitis and OCP or NSAID in the Iranian population is noted.
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Affiliation(s)
- Farzad Firouzi
- Department of Inflammatory Bowel Disease, Research Center for Gastroenterology and Liver Diseases, Taleghani Hospital, Evin, Tehran, Iran.
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47
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Riegler G, Caserta L, Esposito I, De Filippo FR, Bossa F, Esposito P, Russo MI, Carratù R. Worse clinical course of disease in Crohn's patients with previous appendectomy. Eur J Gastroenterol Hepatol 2005; 17:623-627. [PMID: 15879724 DOI: 10.1097/00042737-200506000-00006] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVES The aim of the present study was to assess the effect of previous appendectomy in a series of Crohn's disease (CD) patients on the clinical characteristics and course of disease. METHODS Demographic and clinical data were retrospectively analysed for 129 consecutive outpatients (68 men and 61 women, median age 38 years) with CD. For each patient, information concerning appendectomy, indication for surgery (acute/chronic) and the date of surgery were recorded. The date of the appendectomy in relation to the date of CD diagnosis was carefully assessed in order to evaluate the precise relationship between the two events. A total of 129 CD patients who had not undergone previous appendectomy served as controls. The severity of disease was assessed retrospectively by evaluating the need for systemic steroids, immunosuppressants and surgical treatment for CD, particularly resective procedures. RESULTS Forty-one CD patients (31.8%) underwent appendectomy before the diagnosis of disease. Appendectomy before diagnosis showed a negative association with colonic disease localization and with articular manifestations. In addition, the 41 patients with previous appendectomy had a significantly greater risk of surgery, particularly resective. Multivariate analysis confirmed appendectomy performed before diagnosis as an independent risk factor for surgery; on the contrary, colonic site and inflammatory type of disease were independent factors protecting against surgery. Although current smokers were at an increased risk of surgical treatment, a smoking habit alone did not seem to be relevant at the multivariate analysis. CONCLUSION The results of this study indicate a worse clinical course of CD in patients appendicectomized before diagnosis.
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Affiliation(s)
- Gabriele Riegler
- Medical-Surgical Department of Clinical and Experimental Medicine 'F. Magrassi - A. Lanzara', Second University of Naples, Naples, Italy.
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48
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Adani GL, Baccarani U, Risaliti A. The role of age in the protection of appendicectomy against ulcerative colitis. Gut 2004; 53:1719-20; author reply 1719-20. [PMID: 15479697 PMCID: PMC1774294] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/08/2022]
Affiliation(s)
- G L Adani
- Department of Surgery, University Hospital Udine, Italy
| | - U Baccarani
- Department of Surgery, University Hospital Udine, Italy
| | - A Risaliti
- Department of Surgery, University Hospital Udine, Italy
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49
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Abstract
Evidence is accumulating that both genetic and environmental factors contribute to ulcerative colitis. The most consistent genetic associations have been shown for the MHC locus HLA Class II alleles, but the interleukin-1 family of genes and the multidrug resistance gene MDR1 have also been implicated as genetic susceptibility factors for the development of disease. In addition, there is a relationship between ulcerative colitis and bacterial flora, with an increased number of adherent Bacteroides spp. and Enterobacteriaceae spp. present in inflamed bowel segments. Conversely, cigarette smoking and appendectomy have both been shown to protect against the development of ulcerative colitis. Despite our improved understanding of the genetics and inflammatory mechanisms that underpin this disease, however, the etiology and pathogenesis of ulcerative colitis remain undefined. The diagnosis of ulcerative colitis is being aided by recent advances in diagnostic strategies, including the detection of fecal and serologic markers and the use of wireless capsule endoscopy, but, in the absence of a pathognomonic marker, the definition of this disease remains based on well-established clinical, endoscopic and histologic criteria. In particular, it is difficult to discriminate ulcerative colitis from other forms of colitis, including Crohn's disease, and there seems to be a growing overlap of pathophysiologic processes between ulcerative colitis and post-infectious irritable bowel syndrome. Patients who remain indeterminate between ulcerative colitis and Crohn's disease also continue to be a diagnostic challenge.
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