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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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2
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Yantiss RK. Inflammatory disorders of the appendix. MORSON AND DAWSON'S GASTROINTESTINAL PATHOLOGY 2024:621-634. [DOI: 10.1002/9781119423195.ch29] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Reijntjes MA, de Voogd FAE, Bemelman WA, Hompes R, d'Haens G, Buskens CJ, Gecse KB. Intestinal ultrasound detects an increased diameter and submucosal layer thickness in the appendix of patients with ulcerative colitis compared to healthy controls - a prospective cohort study. Aliment Pharmacol Ther 2023; 57:127-135. [PMID: 36320148 PMCID: PMC10092200 DOI: 10.1111/apt.17267] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Revised: 07/05/2022] [Accepted: 10/11/2022] [Indexed: 11/07/2022]
Abstract
BACKGROUND Increasing evidence suggests that appendicectomy as alternative treatment for ulcerative colitis (UC), especially in patients with histopathological appendiceal inflammation. Intestinal ultrasound (IUS) is a non-invasive diagnostic modality to characterise appendiceal inflammation. AIMS To assess appendiceal IUS characteristics in UC patients and compare findings to healthy controls (HC). METHODS In this prospective study, appendiceal IUS was performed in consecutive UC patients with active (A; n = 35) or quiescent (Q; n = 30) disease and in HC (n = 30). Transverse appendiceal diameter (TAD) and additional IUS parameters (bowel wall thickness, submucosal layer thickness and colour Doppler signal) were assessed. RESULTS The appendix was visualised in 41/65 UC patients (63.1%; A vs. Q: 23/35 vs. 18/30, p = 0.67) and 18/30 (60%) HC. UC patients had a higher TAD (A: 5.5 mm, Q: 5.0 mm, HC: 4.3 mm; A-HC p < 0.01; Q-HC p = 0.01, A-Q p = ns) and submucosal layer thickness (A: 1.0 mm, Q: 1.0 mm, HC: 0.7 mm; A-HC p < 0.01, Q-HC: p = 0.01, A-Q: p = ns) when compared to HC. A TAD ≥6 mm corresponding to an ultrasonographic suspicion of acute appendicitis was mainly reported in A-UC patients (A: 43%; Q: 6%; HC: 0%, p = 0.01) and occurred irrespective of disease extent. However, none of the patients had a clinical suspicion of acute appendicitis. CONCLUSION A TAD ≥6 mm was predominantly seen in A-UC. TAD was higher in UC patients compared to HC irrespective of disease activity and was characterised by an increased submucosal layer thickness. IUS therefore has the potential to identify UC patients with appendiceal inflammation.
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Affiliation(s)
- Maud A Reijntjes
- Department of Surgery, Amsterdam UMC, Amsterdam, the Netherlands.,Amsterdam Gastroenterology Endocrinology Metabolism Research Institute, Amsterdam, the Netherlands
| | - Floris A E de Voogd
- Amsterdam Gastroenterology Endocrinology Metabolism Research Institute, Amsterdam, the Netherlands.,Department of Gastroenterology and Hepatology, Amsterdam UMC, Amsterdam, the Netherlands
| | - Willem A Bemelman
- Department of Surgery, Amsterdam UMC, Amsterdam, the Netherlands.,IBD Unit, Gastroenterology and Endoscopy, IRCCS Ospedale san Raffaele and University Vita-Salute San Raffaele Milano, Milano, Italy
| | - Roel Hompes
- Department of Surgery, Amsterdam UMC, Amsterdam, the Netherlands
| | - Geert d'Haens
- Department of Gastroenterology and Hepatology, Amsterdam UMC, Amsterdam, the Netherlands
| | | | - Krisztina B Gecse
- Department of Gastroenterology and Hepatology, Amsterdam UMC, Amsterdam, the Netherlands
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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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Reijntjes MA, Heuthorst L, Gecse K, Mookhoek A, Bemelman WA, Buskens CJ. Clinical relevance of endoscopic peri-appendiceal red patch in ulcerative colitis patients. Therap Adv Gastroenterol 2022; 15:17562848221098849. [PMID: 35784194 PMCID: PMC9244917 DOI: 10.1177/17562848221098849] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Accepted: 04/19/2022] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Increasing evidence is suggesting appendectomy as an alternative treatment for ulcerative colitis (UC), especially in case of histological appendiceal inflammation. Therefore, preoperative identification of appendiceal inflammation could be beneficial. This study aimed to assess the prevalence of peri-appendiceal red patch (PARP) on colonoscopy. In addition, prognostic relevance of PARP for disease course and its predictive value for histological appendiceal inflammation in patients undergoing appendectomy was assessed. METHODS UC patients undergoing colonoscopy in 2014/2015 were included to determine PARP-prevalence in a cross-sectional study. Findings were correlated to patient and disease characteristics, upscaling of treatment and colectomy rates after cross-sectional colonoscopy. In patients undergoing appendiceal resection, histopathological inflammation was assessed using the Robarts Histopathology Index (RHI). RESULTS In total, 249 patients were included of which 17.7% (44/249) had a PARP. Patients with PARP were significantly younger with a shorter disease course. The majority of patients with PARP (61.4%) was in endoscopic remission. Patients with PARP required more upscaling of medical therapy (81.8% vs. 58.0%, p < 0.01), and more PARP patients underwent colectomy (13.6% vs. 4.9%, p = 0.04). Patients with PARP had a higher median RHI in resection specimens (14 vs. 7, p < 0.01). CONCLUSION PARP was present during colonoscopy regardless disease activity and was predominantly found in UC patients with younger age and shorter disease duration. PARP patients had a more severe course of UC, and in case of appendectomy, more severe histopathological appendiceal inflammation. Appendectomy as an experimental therapy for UC has been suggested to be predominantly effective in UC patients with appendiceal inflammation. This study demonstrates that presence of a PARP on colonoscopy predicts appendiceal inflammation. After consensus has been reached on the therapeutic effect of appendectomy, assessing PARP presence during colonoscopy could therefore contribute to identifying patients most likely to respond.
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Affiliation(s)
- Maud A. Reijntjes
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Lianne Heuthorst
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Krisztina Gecse
- Department of Gastroenterology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Aart Mookhoek
- Institute of Pathology, University of Bern, Bern, Switzerland
| | - Willem A. Bemelman
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands,IBD Unit, Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milano, Italy
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Arjomand Fard N, Armstrong H, Perry T, Wine E. Appendix and Ulcerative Colitis: a Key to Explaining the Pathogenesis and Directing Novel Therapies? Inflamm Bowel Dis 2022; 29:151-160. [PMID: 35749298 PMCID: PMC9825289 DOI: 10.1093/ibd/izac106] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Indexed: 02/05/2023]
Abstract
The vermiform appendix is generally considered a redundant organ, but recent evidence suggests that the appendix could contribute to the pathogenesis of inflammatory bowel diseases, in particular ulcerative colitis (UC), and may even have a therapeutic role; however, mechanisms of the appendix involvement remain unclear. Here, we highlight current evidence on the link between the appendix and UC and consider plausible therapeutic implications. A literature search was conducted using PubMed and PubMed Central from inception to Nov 2021 using the terms "Appendix", "UC", "Appendix & UC," "Appendectomy", and "Peri-appendicular patch," including only articles published in English. Reference lists from the selected studies were manually searched and reviewed to gather additional related reports. Inflammation around the appendix ("peri-appendicular patch") has been frequently observed in UC patients without other cecal involvement, and this inflammation can even precede the onset of UC. Epidemiologic studies propose that appendectomy reduces the risk of developing UC or even the risk of flare after UC is diagnosed, although this remains controversial. We reviewed studies showing altered host-microbe interactions in the appendix in UC, which suggest that the appendix could act as a priming site for disease via alterations in the immune response and changes in microbiota carried distally to the colon. In summary, recent literature suggests a possible role for microbes and immune cells within the appendix; however, the role of the appendix in the pathogenesis of UC remains unclear. Further research could clarify the therapeutic potential related to this organ.
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Affiliation(s)
- Nazanin Arjomand Fard
- Centre of Excellence for Gastrointestinal Inflammation and Immunity Research, University of Alberta, Edmonton, AB, T6G 2X8, Canada,Department of Physiology, University of Alberta, Edmonton, AB T6G 1C9, Canada
| | - Heather Armstrong
- Centre of Excellence for Gastrointestinal Inflammation and Immunity Research, University of Alberta, Edmonton, AB, T6G 2X8, Canada,Department of Pediatrics, University of Alberta, Edmonton Clinic Health Academy, Room 4-577, 11405 87th Ave, Edmonton, AB T6G 1C9, Canada,Department of Internal Medicine, University of Manitoba, Winnipeg, MB R3E 3P4, Canada
| | - Troy Perry
- Centre of Excellence for Gastrointestinal Inflammation and Immunity Research, University of Alberta, Edmonton, AB, T6G 2X8, Canada,Department of Surgery, University of Alberta, Edmonton, AB T6G 1C9, Canada
| | - Eytan Wine
- Address correspondence to: Dr. Eytan Wine, Department of Pediatrics, University of Alberta, Edmonton Clinic Health Academy, Room 4-577, 11405 87th Ave, Edmonton, AB T6G 1C9, Canada ()
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de Costa A. The appendix‐mucosal immunity and tolerance in the gut: consequences for the syndromes of appendicitis and its epidemiology. ANZ J Surg 2022; 92:653-660. [PMID: 35152541 PMCID: PMC9304207 DOI: 10.1111/ans.17522] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Revised: 01/06/2022] [Accepted: 01/19/2022] [Indexed: 12/16/2022]
Abstract
The cause of appendicitis is unknown. A review is presented across diverse sources relating to the biology of the appendix and its perturbations. A mechanistic model of the function of the appendix is presented, and its application to the syndromes and consequences of appendicitis is described.
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Affiliation(s)
- Alan de Costa
- College of Medicine and Dentistry James Cook University, Cairns Clinical School, Cairns Hospital Cairns Queensland Australia
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8
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Bandyopadhyay A, Majumdar K, Mishra V. Non-neoplastic Lesions of the Appendix. SURGICAL PATHOLOGY OF THE GASTROINTESTINAL SYSTEM 2022:481-519. [DOI: 10.1007/978-981-16-6395-6_13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Kmeid M, Arker SH, Petchers A, Lukose G, Li H, Lee EC, Qualia CM, Arslan ME, Lee H. Appendiceal inflammation in colectomy is independently correlated with early pouchitis following ileal pouch anal anastomosis in ulcerative colitis and indeterminate colitis. Ann Diagn Pathol 2021; 55:151838. [PMID: 34626936 DOI: 10.1016/j.anndiagpath.2021.151838] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2021] [Revised: 09/23/2021] [Accepted: 09/28/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Appendiceal inflammation in colectomy is one of the histologic predictors of pouchitis in ulcerative colitis (UC) following ileal pouch anal anastomosis (IPAA). Fecal calprotectin level has been shown to increase 2 months prior to the onset of pouchitis. We evaluated whether inflammation and calprotectin expression in appendiceal specimens correlate with early-onset pouchitis in UC and indeterminate colitis (IC). MATERIALS AND METHODS IPAA (2000-2018) cases with appendix blocks available in colectomy specimens were identified (n = 93, 90 UC, 3 IC). Histologic features thought to predict pouchitis were evaluated. The degree of appendiceal inflammation was scored. Calprotectin immunostain was performed on the appendix blocks and the extent of mucosal staining was quantified. Electronic medical records were reviewed for demographics, smoking history, clinical pouchitis, time of onset of pouchitis, and clinical and endoscopic components of the Pouchitis Disease Activity Index (PDAI) score. Follow-up pouch biopsies were reviewed and scored to generate histologic PDAI score, when available. RESULTS Among the patients with clinical pouchitis (n = 73), moderate to severe appendiceal inflammation independently correlated with earlier pouchitis compared to no/mild inflammation (median time to pouchitis 12.0 vs. 23.8, log rank p = 0.016). Calprotectin staining correlated with inflammatory scores of the appendix (Spearman's rho, r = 0.630, p < 0.001) but not with early pouchitis (p > 0.05). CONCLUSIONS The presence of moderate to severe appendiceal inflammation at the time of colectomy was associated with a shorter time to pouchitis following IPAA. Calprotectin immunostain may be used to demonstrate the presence of inflammation in the appendix but its role in predicting early pouchitis remains limited.
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Affiliation(s)
- Michel Kmeid
- Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY, USA.
| | - Soe Htet Arker
- Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY, USA.
| | - Adam Petchers
- Department of Surgery, Albany Medical Center, Albany, NY, USA.
| | | | - Hua Li
- Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY, USA.
| | - Edward C Lee
- Department of Surgery, Albany Medical Center, Albany, NY, USA.
| | - Cary M Qualia
- Department of Pediatrics, Albany Medical Center, Albany, NY, USA.
| | - Mustafa Erdem Arslan
- Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY, USA.
| | - Hwajeong Lee
- Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY, USA.
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Kobayashi Y, Ohfuji S, Kondo K, Fukushima W, Sasaki S, Kamata N, Yamagami H, Fujiwara Y, Suzuki Y, Hirota Y. Association of Dietary Fatty Acid Intake With the Development of Ulcerative Colitis: A Multicenter Case-Control Study in Japan. Inflamm Bowel Dis 2021; 27:617-628. [PMID: 32507894 DOI: 10.1093/ibd/izaa140] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND Dietary fatty acids can affect chronic intestinal inflammation and have been reported to be associated with the development of ulcerative colitis (UC), mainly in Europe and the United States. The association of dietary intake of fatty acids and the risk for UC was investigated in Japan, where dietary habits lead to lower meat and higher fish consumption than in Western countries. METHODS A multicenter case-control study of 83 newly diagnosed patients with UC and 128 age- and sex-matched control patients in the hospital was conducted from 2008 to 2014. Dietary fatty acid intake in the preceding 1 month and 1 year were examined using a self-administered diet history questionnaire that was developed for Japanese people. RESULTS About 92% of patients had experienced the first symptoms of UC within the preceding 11 months. Regarding dietary habits in the preceding year, the risk for UC was significantly decreased in patients who consumed n-6/n-3 polyunsaturated fatty acids at a ratio of ≥5.2 (odds ratio [OR] = 0.26; 95% confidence interval [CI], 0.10-0.68). Conversely, an increased risk for UC was observed in the highest tertiles of consumption of docosahexaenoic acid (OR = 7.22; 95% CI, 2.09-24.95), eicosapentaenoic acid (OR = 6.91; 95% CI, 1.88-25.44), and docosapentaenoic acid (OR = 4.83; 95% CI, 1.56-14.95). CONCLUSIONS The ratio of n-6/n-3 polyunsaturated fatty acid intake was associated with a decreased risk for UC development. However, high intakes of docosahexaenoic acid, eicosapentaenoic acid, and docosapentaenoic acid may increase the risk for UC development.
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Affiliation(s)
- Yumie Kobayashi
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Satoko Ohfuji
- Department of Public Health, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Kyoko Kondo
- Administration Division, Osaka City University Hospital, Osaka, Japan
| | - Wakaba Fukushima
- Department of Public Health, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Satoshi Sasaki
- Department of Social and Preventive Epidemiology, School of Public Health, The University of Tokyo, Tokyo, Japan
| | - Noriko Kamata
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Hirokazu Yamagami
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Yasuhiro Fujiwara
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Yasuo Suzuki
- Department of Internal Medicine, Sakura Medical Center, Toho University, Chiba, Japan
| | - Yoshio Hirota
- Department of Public Health, Osaka City University Graduate School of Medicine, Osaka, Japan.,College of Healthcare Management, Fukuoka, Japan
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Etienne D, Ofosu A, Ona MA, Reddy M. Microcarcinoid and Ulcerative Colitis: Case Report and Literature Review. Cureus 2020; 12:e8803. [PMID: 32724749 PMCID: PMC7381878 DOI: 10.7759/cureus.8803] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Gastrointestinal microcarcinoid tumors are rare, and the concomitant diagnosis of microcarcinoid tumor and inflammatory bowel disease is even rarer. A 54-year-old African American male with an eight-year history of ulcerative colitis (UC) presented with a three-day history of abdominal pain and bloody diarrhea. Rectal biopsy on colonoscopy was notable for small nests of neuroendocrine cell proliferation in the mucosa consistent with a diagnosis of microcarcinoid tumor. Whether the incidence is coincidental or represents an epiphenomenon of chronic inflammation remains to be determined.
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Affiliation(s)
- Denzil Etienne
- Gastroenterology and Hepatology, The Brooklyn Hospital Center, Academic Affiliate of the Icahn School of Medicine at Mount Sinai, Clinical Affiliate of the Mount Sinai Hospital, Brooklyn, USA
| | - Andrew Ofosu
- Gastroenterology, The Brooklyn Hospital Center, Affiliate of the Mount Sinai Hospital, Brooklyn, USA
| | - Mel A Ona
- Gastroenterology and Hepatology, Pali Momi Medical Center, Honolulu, USA
| | - Madhavi Reddy
- Gastroenterology and Hepatology, The Brooklyn Hospital Center, Affiliate of the Icahn School of Medicine at Mount Sinai, Brooklyn, USA
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12
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Parian A, Limketkai B, Koh J, Brant SR, Bitton A, Cho JH, Duerr RH, McGovern DP, Proctor DD, Regueiro MD, Rioux JD, Schumm P, Taylor KD, Silverberg MS, Steinhart AH, Hernaez R, Lazarev M. Appendectomy does not decrease the risk of future colectomy in UC: results from a large cohort and meta-analysis. Gut 2017; 66:1390-1397. [PMID: 27196594 PMCID: PMC5065377 DOI: 10.1136/gutjnl-2016-311550] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2016] [Revised: 03/15/2016] [Accepted: 03/21/2016] [Indexed: 12/12/2022]
Abstract
OBJECTIVES Early appendectomy is inversely associated with the development of UC. However, the impact of appendectomy on the clinical course of UC is controversial, generally favouring a milder disease course. We aim to describe the effect appendectomy has on the disease course of UC with focus on the timing of appendectomy in relation to UC diagnosis. DESIGN Using the National Institute of Diabetes and Digestive and Kidney Diseases Inflammatory Bowel Disease Genetics Consortium database of patients with UC, the risk of colectomy was compared between patients who did and did not undergo appendectomy. In addition, we performed a meta-analysis of studies that examined the association between appendectomy and colectomy. RESULTS 2980 patients with UC were initially included. 111 (4.4%) patients with UC had an appendectomy; of which 63 were performed prior to UC diagnosis and 48 after diagnosis. In multivariable analysis, appendectomy performed at any time was an independent risk factor for colectomy (OR 1.9, 95% CI 1.1 to 3.1), with appendectomy performed after UC diagnosis most strongly associated with colectomy (OR 2.2, 95% CI 1.1 to 4.5). An updated meta-analysis showed appendectomy performed either prior to or after UC diagnosis had no effect on colectomy rates. CONCLUSIONS Appendectomy performed at any time in relation to UC diagnosis was not associated with a decrease in severity of disease. In fact, appendectomy after UC diagnosis may be associated with a higher risk of colectomy. These findings question the proposed use of appendectomy as treatment for UC.
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Affiliation(s)
- Alyssa Parian
- Division of Gastroenterology, The Johns Hopkins School of Medicine, Baltimore, MD, USA
| | - Berkeley Limketkai
- Division of Gastroenterology, The Johns Hopkins School of Medicine, Baltimore, MD, USA, Division of Gastroenterology & Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Joyce Koh
- Division of Gastroenterology, The Johns Hopkins School of Medicine, Baltimore, MD, USA
| | - Steven R. Brant
- Division of Gastroenterology, The Johns Hopkins School of Medicine, Baltimore, MD, USA
| | - Alain Bitton
- Division of Gastroenterology, McGill University, Montreal, Québec, Canada
| | - Judy H. Cho
- Division of Gastroenterology, Mount Sinai Hospital, New York, NY, USA
| | - Richard H. Duerr
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh, Pittsburgh, PA, USA
| | - Dermot P. McGovern
- Division of Gastroenterology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Deborah D. Proctor
- Division of Digestive Disease, Yale School of Medicine, New Haven, CT, USA
| | - Miguel D. Regueiro
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh, Pittsburgh, PA, USA
| | - John D. Rioux
- Division of Medicine, Université de Montréal, Montreal, Québec, Canada
| | - Phil Schumm
- Department of Health Studies, University of Chicago, Chicago, IL, USA
| | - Kent D. Taylor
- Division of Gastroenterology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | | | | | - Ruben Hernaez
- Division of Gastroenterology, The Johns Hopkins School of Medicine, Baltimore, MD, USA
| | - Mark Lazarev
- Division of Gastroenterology, The Johns Hopkins School of Medicine, Baltimore, MD, USA
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Appendectomy and the Risk of Colectomy in Ulcerative Colitis: A National Cohort Study. Am J Gastroenterol 2017; 112:1311-1319. [PMID: 28653667 DOI: 10.1038/ajg.2017.183] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2017] [Accepted: 05/21/2017] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Ulcerative colitis (UC) is a chronic inflammatory disease usually responding well to anti-inflammatory drugs but many patients will still need colectomy. Appendectomy is associated with a lower risk of later developing UC. We aimed to assess the longitudinal relationship between appendectomy, appendicitis, and disease course in UC patients. METHODS A national cohort of UC patients with a diagnosis in 1964-2010 was identified from the Swedish National Patient Register that also provided information regarding appendicitis and/or appendectomy before or after the UC diagnosis. The risk for colectomy and UC-related hospital admissions was evaluated. RESULTS Among 63,711 UC patients, 2,143 had appendectomy and 7,690 underwent colectomy. Appendectomy for appendicitis before 20 years of age and for non-appendicitis at all ages before UC diagnosis was associated with a lower risk of colectomy (hazard ratio (HR) 0.44, 0.27-0.72 and HR 0.62, 0.43-0.90, respectively), and fewer hospital admissions (incidence rate ratio (IRR) 0.68, 95% confidence interval (CI) 0.64-0.73 and IRR 0.54, 0.47-0.63, respectively). Appendectomy for appendicitis after the UC diagnosis was associated with a higher risk of colectomy (HR 1.56, 1.20-2.03), whereas no such association was found for other pathology (HR 1.40, 0.79-2.47). CONCLUSIONS Appendectomy early in life and before developing UC is associated with a lower risk of colectomy as well as UC-related hospital admissions. Appendectomy for appendicitis after established UC appears associated with a worse disease course, with an increased rate of subsequent colectomy.
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Kooij IA, Sahami S, Meijer SL, Buskens CJ, Te Velde AA. The immunology of the vermiform appendix: a review of the literature. Clin Exp Immunol 2016; 186:1-9. [PMID: 27271818 DOI: 10.1111/cei.12821] [Citation(s) in RCA: 113] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2016] [Revised: 05/30/2016] [Accepted: 05/31/2016] [Indexed: 12/19/2022] Open
Abstract
This literature review assesses the current knowledge about the immunological aspects of the vermiform appendix in health and disease. An essential part of its immunological function is the interaction with the intestinal bacteria, a trait shown to be preserved during its evolution. The existence of the appendiceal biofilm in particular has proved to have a beneficial effect for the entire gut. In assessing the influence of acute appendicitis and the importance of a normally functioning gut flora, however, multiple immunological aspects point towards the appendix as a priming site for ulcerative colitis. Describing the immunological and microbiotical changes in the appendix during acute and chronic inflammation of the appendix, this review suggests that this association becomes increasingly plausible. Sustained by the distinct composition of cells, molecules and microbiota, as well as by the ever more likely negative correlation between the appendix and ulcerative colitis, the idea of the appendix being a vestigial organ should therefore be discarded.
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Affiliation(s)
- I A Kooij
- Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, Amsterdam, the Netherlands
| | - S Sahami
- Department of Surgery, Academic Medical Center, Amsterdam, the Netherlands
| | - S L Meijer
- Department of Pathology, Academic Medical Center, Amsterdam, the Netherlands
| | - C J Buskens
- Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, Amsterdam, the Netherlands
| | - A A Te Velde
- Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, Amsterdam, the Netherlands
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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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Lee HS, Park SH, Yang SK, Kim SO, Soh JS, Lee S, Bae JH, Lee HJ, Yang DH, Kim KJ, Ye BD, Byeon JS, Myung SJ, Kim JH. Appendectomy and the clinical course of ulcerative colitis: a retrospective cohort study and a nested case-control study from Korea. J Gastroenterol Hepatol 2015; 30:470-7. [PMID: 25159898 DOI: 10.1111/jgh.12707] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/12/2014] [Indexed: 12/17/2022]
Abstract
BACKGROUND AND AIM Appendectomy protects against the development of ulcerative colitis (UC). However, the relationship between appendectomy and the clinical course of UC is complex, and could be impacted by a number of variables. The aim of this study was to compare the clinical course of UC between appendectomized patients and nonappendectomized patients in Korea. METHODS Data on 2648 UC patients were retrieved from the Inflammatory Bowel Disease registry at Asan Medical Center. This retrospective cohort study compared the clinical course of UC in 68 patients who received an appendectomy before their UC diagnosis and 2544 patients who did not receive this procedure. A nested case-control study was also conducted to compare the disease course before and after appendectomy in 36 patients who received this surgery after UC diagnosis. To control for potential confounders, 144 matched controls were retrieved from among 2544 nonappendectomized patients RESULTS In the retrospective cohort study, an appendectomy before UC diagnosis demonstrated no influence on disease extent at diagnosis, rates of medication use, proximal disease extension, or colectomy. The 10- and 20-year probabilities of receiving a colectomy were 12.7% and 20.6%, respectively, in appendectomized patients, in comparison with 8.9% and 16.4%, respectively, in nonappendectomized patients (P = 0.81). According to the nested case-control study, an appendectomy after UC diagnosis did not change the subsequent disease course in terms of medication use, proximal disease extension, or hospital admission rate. The adjusted ratio of hospital admissions after appendectomy versus before appendectomy was 1.01 (95% confidence interval = 0.46-2.23; P = 0.97). CONCLUSIONS Appendectomies performed before or after UC diagnosis do not affect its clinical course in the Korean population.
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Affiliation(s)
- Ho-Su Lee
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
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Park SH, Loftus EV, Yang SK. Appendiceal skip inflammation and ulcerative colitis. Dig Dis Sci 2014; 59:2050-7. [PMID: 24705639 DOI: 10.1007/s10620-014-3129-z] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2014] [Accepted: 03/20/2014] [Indexed: 12/13/2022]
Abstract
In recent decades, the appearance of inflammation near the appendix in patients with distal ulcerative colitis (UC) has been highlighted. Many epidemiological studies have confirmed the link between appendectomy and decreased incidence of UC. However, the clinical significance of appendiceal orifice inflammation (AOI) or peri-appendiceal red patch (PARP) as a "skip lesion" in UC has not been well elucidated. In this review, we summarized the literature regarding AOI/PARP and the role of this lesion in relation to UC. Since the appendiceal "skip area" in UC was first described in 1958, several reports using histologic examination of colectomy specimens and colonoscopy have been published. AOI/PARP has been more frequently associated with distal, mild UC than extensive, severe disease. Although it is still controversial, AOI/PARP seems to have little prognostic implication in the disease course of UC, including remission, relapse and proximal disease extension. However, some case reports have raised the possibility of a relationship between AOI/PARP and appendiceal neoplasms such as appendiceal cystadenoma and appendiceal adenocarcinoma. In addition, some investigators have treated UC patients who were resistant to conventional medical therapy with appendectomy and have reported inconsistent therapeutic effect. Further research may lead to the discovery of etiologic and pathogenic roles of appendiceal inflammation in UC.
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Affiliation(s)
- Sang Hyoung Park
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, Korea
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Mantani Y, Nishida M, Yuasa H, Yamamoto K, Takahara EI, Omotehara T, Udayanga KGS, Kawano J, Yokoyama T, Hoshi N, Kitagawa H. Ultrastructural and histochemical study on the Paneth cells in the rat ascending colon. Anat Rec (Hoboken) 2014; 297:1462-71. [PMID: 24788798 DOI: 10.1002/ar.22937] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2014] [Accepted: 04/09/2014] [Indexed: 01/06/2023]
Abstract
Paneth cells (PCs) contribute to the host defense against indigenous bacteria in the small intestine. We found Paneth cell-like cells (PLCs) in the rat ascending colon, but the nature of PLCs is never clarified. Therefore, the present study aimed to clarify the cytological characteristics of PLCs and discuss their cellular differentiation. PLCs were localized in the bases of intestinal crypts, especially follicle-associated intestinal crypts in proximal colonic lymphoid tissue, but were very seldom found in the ordinary intestinal crypts of the ascending colon. PLCs possessed specific granules with highly electron-dense cores and haloes, as well as PCs in the small intestine. The secretory granules of PLCs were positive for PAS reaction, lysozyme and soluble phospholipase A2, but negative for Alcian blue staining, β-defensin-1 and -2, as well as the ones of PCs. Furthermore, intermediate cells possessing both the PLC-specific granules and the mucus granules similar to those of goblet cells (GCs) were occasionally found in the vicinity of PLCs. Intermediate cells ranged from goblet cell-like cells rich in mucus granules to PLC-like cells with few mucus granules. The cellular condensation and fragmentation were exclusively found in PLCs but never seen in intermediate cells or GCs. The PLCs, which were identified as PC, were suggested to be transformed from GCs through intermediate cells and finally to die by apoptosis in intestinal crypts of proximal colonic lymphoid tissue in the rat ascending colon.
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Affiliation(s)
- Youhei Mantani
- Laboratory of Histophysiology, Department of Bioresource Science, Graduate School of Agricultural Science, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe, Hyogo, Japan
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Gardenbroek TJ, Eshuis EJ, Ponsioen CIJ, Ubbink DT, D'Haens GRAM, Bemelman WA. The effect of appendectomy on the course of ulcerative colitis: a systematic review. Colorectal Dis 2012; 14:545-53. [PMID: 21689293 DOI: 10.1111/j.1463-1318.2011.02600.x] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
AIM Previous studies have shown significantly lower appendectomy rates in ulcerative colitis (UC) patients compared with healthy controls. Evidence indicating that the appendix has an immunomodulatory role in UC has been accumulating. To examine the latest evidence on the effect of appendectomy on the disease course of UC. METHOD PubMed, The Cochrane Library and EMBASE were searched. Primary end-points were number of relapses, use of steroids, number of hospital admissions and number of colectomies. RESULTS The search resulted in six observational studies (five case-control studies and one cohort study) totalling 2532 patients. Owing to clinical heterogeneity, no meta-analysis could be conducted. One study found lower relapse rates in patients appendectomized before the onset of UC [absolute risk reduction (ARR)=21.5%; 95% CI: 1.71-45.92%]. Another two studies found a reduced requirement for immunosuppression in appendectomized patients (ARR=20.2%; 95% CI: 9.67-30.46% in the first study and ARR=21.4%; 95% CI: 10.32-32.97% in the second study). In addition, one study found lower colectomy rates in nonappendectomized patients (ARR=8.7%; 95% CI: 1.29-18.66%) and two studies found lower colectomy rates in appendectomized patients (ARR=21.4%; 95% CI: 13.17-28.79% in the first study and ARR=18.7%; 95% CI: 7.50-29.97% in the second study). CONCLUSION There are limited and conflicting data available regarding the effect of appendectomy on the disease course of UC. Most studies suggest a beneficial effect and the minority find no, or a negative, effect.
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Affiliation(s)
- T J Gardenbroek
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
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20
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The vermiform appendix and recurrent Clostridium difficile infection: a curious connection. Clin Gastroenterol Hepatol 2011; 9:1017-9. [PMID: 21893132 PMCID: PMC5320954 DOI: 10.1016/j.cgh.2011.08.025] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2011] [Revised: 08/22/2011] [Accepted: 08/27/2011] [Indexed: 02/06/2023]
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Noaki R, Kawahara H, Watanabe K, Kobayashi S, Uchiyama K, Yanaga K. Appendiceal Mucocele Detected under Treatment of Ulcerative Colitis. Case Rep Gastroenterol 2009; 3:360-365. [PMID: 21103254 PMCID: PMC2988930 DOI: 10.1159/000242475] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
A 33-year-old female patient with ulcerative colitis was referred to our outpatient clinic in January 2008 with right lower abdominal pain without bloody diarrhea. Colonoscopy found mild proctosigmoiditis and a submucoal tumor with a maximal diameter of 5 cm in the cecum. Computed tomography revealed a large, hypodense, cystic cylindrical structure extending to the pelvic space. For severe pain, she underwent partial resection of the cecum including the tumor in March 2008. Intraoperatively, the vermiform appendix was swollen like a sausage and compressing the cecum, which accounted for what appeared to be a submucosal tumor like a volcano by endoscopy. Lymphadenectomy was not performed because malignancy was not suspected. In the surgical specimen, the vermiform appendix was spindle-shaped and contained a large quantity of viscous liquid. Postoperative pathological diagnosis was mucinous cystadenoma, and no cancer cells were present in the viscous liquid within the vermiform appendix. The patient left the hospital 7 days postoperatively, and her colitis remains in remission without any complications.
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Affiliation(s)
- Rohta Noaki
- Department of Surgery, Kashiwa Hospital, Jikei University School of Medicine, Chiba, Japan
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22
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Yantiss RK, Odze RD. Pitfalls in the interpretation of nonneoplastic mucosal biopsies in inflammatory bowel disease. Am J Gastroenterol 2007; 102:890-904. [PMID: 17324129 DOI: 10.1111/j.1572-0241.2007.01105.x] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
This review provides a summary of common diagnostic problems encountered by both pathologists and gastroenterologists when evaluating patients with diarrhea and in whom inflammatory bowel disease (IBD) is suspected. The two most common forms of IBD, ulcerative colitis (UC) and Crohn's disease (CD), may, in certain settings, show overlapping endoscopic and pathologic features, potentially resulting in diagnostic confusion. For instance, some cases of UC may show unusual CD-like features, such as rectal sparing, discontinuous disease, aphthous ulceration, ileal or extracolonic involvement, and granulomatous inflammation, all of which may be evident in mucosal biopsy specimens. CD may also present as a diffuse, superficial pancolitis with ileal sparing that mimics the endoscopic and histologic appearance of UC. Furthermore, other forms of colitis, such as microscopic colitis, diverticulitis, diversion colitis, and nonsteroidal anti-inflammatory drug (NSAID)-induced colonic injury may also show IBD-like changes in mucosal biopsies. The potential diagnostic pitfalls faced by physicians, as well as features that aid in the distinction among these entities, are discussed in detail in this review.
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Affiliation(s)
- Rhonda K Yantiss
- Department of Pathology and Laboratory Medicine of the Weill Medical College of Cornell University, New York, New York, USA
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23
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Olivares D, Gisbert JP, Gamallo C, Maté-Jiménez J. Immunological changes at rectal mucosa in appendectomised subjects and inhabitants of developing countries. GASTROENTEROLOGIA Y HEPATOLOGIA 2007; 30:57-60. [PMID: 17335710 DOI: 10.1157/13099263] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
AIM It has been suggested that appendicitis protects against ulcerative colitis. We hypothesize that early poor hygiene protects against ulcerative colitis (UC) and predisposes to appendicitis. Our aim was to elucidate the immunological characteristics of rectal mucosa in two populations protected against UC development: appendectomised subjects and inhabitants of developing countries. METHODS this was an age-matched prospective case-control study. Each consecutive individual case appendectomised (group A) was compared to another control from a developing country (group B) and to a control from the general population (group C). Four biopsies from rectal mucosa were taken from all subjects, two for histological and two for histochemical study; specific antibodies were used for T lymphocytes CD3+, CD4+, CD8+ and B lymphocytes CD20+ populations. RESULTS Mucosa samples of 45 non-smoker healthy subjects were studied, of which 15 were from group A, 15 from group B and 15 from group C. In appendectomised subjects, the proportion of CD8+ cells was higher than in the control group (p<0.001), but similar to that in B group. The proportion of CD3+ and CD20+ cells was significatively lower than in Ecuadorians, but similar to the control group. In Ecuadorians, the proportion of CD3+ and CD8+ cells was significatively higher than in the control group (p<0.001), and were similar to that of CD20+. There were no significant differences in the proportion of CD4+. CONCLUSION Appendectomy and deficient environmental hygiene are associated with an increase of CD8+ T lymphocytes in the rectal mucosa. Moreover, deficient environmental hygiene is associated with an increase of CD3+ and CD8+ lymphocytes. The CD8+ increase is the only common significant alteration in the mucosa of both groups protected against the development of ulcerative colitis, suggesting that the factors causing changes in lamina propria lymphocytes of both groups are different.
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Fogt F, Deren JJ, Nusbaum M, Wellmann A, Ross HM. Pouchitis in Ulcerative Colitis: Correlation between Predictors from Colectomy Specimens and Clinico-Histological Features. Eur Surg Res 2006; 38:407-13. [PMID: 16864967 DOI: 10.1159/000094669] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2006] [Accepted: 06/02/2006] [Indexed: 01/09/2023]
Abstract
Pouchitis after restorative proctocolectomy for ulcerative colitis is usually of ill-defined etiology and is encountered with sclerosing cholangitis, bacterial overgrowth, and ischemia. Recently, appendiceal involvement, ileitis, and fissures in the colectomy specimen have been associated with short- and long-term development of pouchitis. To corroborate these recent findings, the histology of 40 colectomies (70% males; mean age 46.3 years, age range 20-70 years; mean follow-up period 3.7 years, range 1-13 years) with yearly follow-up biopsies was correlated with pouchitis and clinical symptoms. Appendicitis, fissures, and ileitis were present in 47, 45 and 5% of the patients, respectively. Pouchitis in patients with appendicitis or with fissures was noted in 44 and 50% at first biopsy and in 70 and 58% during follow-up (p = NS). Of the patients without appendicitis or without fissures, 33 and 33% demonstrated pouchitis at the first biopsy and 30 and 55% during follow-up (p = NS). Clinico-histological correlation revealed normal/near-normal biopsies with the lowest clinical severity score in 77% and with the highest clinical score in 43% (p < 0.025). The histological findings of appendiceal involvement, fissuring ulcers, and ileitis in colectomies for ulcerative colitis do not correlate with the finding of pouchitis in early or late pouch biopsies. A high clinical suspicion score is frequently not correlated with significant inflammation of the pouch.
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Affiliation(s)
- F Fogt
- Department of Pathology, Presbyterian Medical Center, University of Pennsylvania, Philadelphia, PA 19104, USA.
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Matsushita M, Takakuwa H, Matsubayashi Y, Nishio A, Ikehara S, Okazaki K. Appendix is a priming site in the development of ulcerative colitis. World J Gastroenterol 2005; 11:4869-74. [PMID: 16097061 PMCID: PMC4398739 DOI: 10.3748/wjg.v11.i31.4869] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: The role of the appendix has been highlighted in the pathogenesis of ulcerative colitis (UC). The aims of this study were to elucidate the immuno-imbalances in the appendix of UC patients, and to clarify the role of the appendix in the development of UC.
METHODS: Colonoscopic biopsy specimens of the appendix, transverse colon, and rectum were obtained from 86 patients with UC: active pancolitis (A-Pan; n = 15), active left-sided colitis (A-Lt; n = 25), A-Lt with appendiceal involvement (A-Lt/Ap; n = 10), inactive pancolitis (I-Pan; n = 14), and inactive left-sided colitis (I-Lt; n = 22), and from controls. In the isolated mucosal T cells, the CD4/CD8 ratio and proportion of activated CD4+ T cells were investigated, and compared with controls.
RESULTS: In the appendix, the CD4/CD8 ratio significantly increased in A-Lt and A-Lt/Ap. The ratio in the appendix also tended to increase in A-Pan. In the rectum, the ratio significantly increased in all UC groups. In the appendix, the proportion of CD4+CD69+ (early activation antigen) T cells significantly increased in all UC groups. In the rectum, the proportion of CD4+CD69+ T cells significantly increased only in A-Pan. The proportion of CD4+HLA-DR+ (mature activation antigen) T cells significantly increased only in the rectum of A-Pan, but not in the other areas of any groups.
CONCLUSION: The increased CD4/CD8 ratio and predominant infiltration of CD4+CD69+ T cells in the appendix suggest that the appendix is a priming site in the development of UC.
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Affiliation(s)
- Mitsunobu Matsushita
- Third Department of Internal Medicine, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi, Osaka 570-8506, Japan.
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26
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Byeon JS, Yang SK, Myung SJ, Pyo SI, Park HJ, Kim YM, Lee YJ, Hong SS, Kim KJ, Lee GH, Jung HY, Hong WS, Kim JH, Min YI. Clinical course of distal ulcerative colitis in relation to appendiceal orifice inflammation status. Inflamm Bowel Dis 2005; 11:366-71. [PMID: 15803026 DOI: 10.1097/01.mib.0000164018.06538.6e] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
BACKGROUND Although appendiceal orifice inflammation (AOI) is frequently observed as a skip lesion of ulcerative colitis (UC), its clinical significance is not clearly understood. We aimed to evaluate whether AOI is associated with the clinical course of UC. METHODS Ninety-four patients with newly diagnosed distal UC were prospectively enrolled at the Asan Medical Center between March 1996 and October 2002. Clinical features and colonoscopic findings during the follow-up period were analyzed in relation to initial AOI status. RESULTS Forty-eight patients were found to be initially AOI-positive and 46 to be initially AOI-negative. We found no difference in the baseline demographics and clinical characteristics between these two groups. The median follow-up periods for AOI-positive and AOI-negative groups were 45 and 41 months, respectively. Clinical remission was achieved in all patients of each group. The cumulative risk of relapse at 1, 3, and 5 years after remission was 31.2%, 59.8%, and 69.2%, respectively, in the AOI-positive group and 17.4%, 46.5%, and 67.2%, respectively, in the AOI-negative group (P = 0.124). The cumulative risk of proximal disease extension at 1, 3, and 5 years after diagnosis was 17.9%, 24.9%, and 44.5%, respectively, in the AOI-positive group and 9.8%, 21.5%, and 43.9%, respectively, in the AOI-negative group (P = 0.522). Proctocolectomy was performed in no patients in the AOI-positive group and in 1 patient in the AOI-negative group. No mortalities were observed in either group. CONCLUSIONS In patients with distal UC, AOI may have no prognostic implications in terms of remission, relapse, or proximal disease extension.
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Affiliation(s)
- Jeong-Sik Byeon
- Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
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Lakatos PL, Gyori G, Halasz J, Fuszek P, Papp J, Jaray B, Lukovich P, Lakatos L. Mucocele of the appendix: an unusual cause of lower abdominal pain in a patient with ulcerative colitis. A case report and review of literature. World J Gastroenterol 2005; 11:457-459. [PMID: 15637769 PMCID: PMC4205363 DOI: 10.3748/wjg.v11.i3.457] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2004] [Revised: 04/10/2004] [Accepted: 05/25/2004] [Indexed: 02/06/2023] Open
Abstract
The authors report the case of a 60-year-old male patient. In November 2001 he developed intestinal symptoms of bloody diarrhea and abdominal pain. Colononoscopy and biopsy established the diagnosis of ulcerative colitis (proctosigmoiditis). The disease activity was moderate at the beginning. No significant laboratory alterations were found (including CEA, CA19-9), and mesalazine was started orally. He was in remission until November 2003, when he was admitted to our Outpatient Clinic for upper and right lower abdominal pain and bloody diarrhea. Colonoscopy found proctosigmoiditis with a moderate activity, gastroscopy revealed chronic gastritis, laboratory data was normal. Treatment was amended with mesalazine clysma and methylprednisolone (16 mg) orally. Symptoms ameliorated; however, right lower abdominal pain persisted. US and CT examination demonstrated a pericecal cystic mass (11 cm x 3.5 cm). At first pericecal abscess was suspected, as the previous US examination (6 mo earlier) had revealed normal findings. Fine needle aspiration was performed. Cytology confirmed the diagnosis of mucocele. The patient underwent partial cecum resection and extirpation of the mucocele. He recovered well and the final histology revealed a cystadenoma of the appendix. Follow up was started. The patient is now free of symptoms. Although primary adenocarcinoma of the appendix is uncommon, the authors emphasize that preoperative diagnosis of an underlying malignancy in a mucocele is important for patient management; however, it is difficult on imaging studies.
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Lucci E, Lattuneddu A, Valpiani D, Ricci E, Dubini A, Garcea D. Skip lesion of the cecum associated with proctitis: an atypical case of ulcerative colitis. Dig Liver Dis 2004; 36:847-51. [PMID: 15646434 DOI: 10.1016/j.dld.2004.01.029] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The authors report the clinical case of a patient who underwent total colectomy for acute ulcerative colitis. The unusual element in this case was the presence of a lesion ('skip lesion'), typical of ulcerative colitis, in the periappendiceal area of the cecum, which was discontinuous to the main site of disease located in the rectum and left colon. The presence of skip lesions, whose clinicopathological relevance is still unknown, would seem to disprove the widely held view that ulcerative colitis involves only the mucous membrane of the large intestine, with inflammatory processes of varying intensity, but without intervening normal areas. The alteration in mucosal immune response by sharing of some factors as bacterial flora, stasis and secretory products is a suggestive pathogenetic supposition.
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Affiliation(s)
- E Lucci
- GB Morgagni Hospital, Forlì, Italy.
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Yantiss RK, Sapp HL, Farraye FA, El-Zammar O, O'Brien MJ, Fruin AB, Stucchi AF, Brien TP, Becker JM, Odze RD. Histologic predictors of pouchitis in patients with chronic ulcerative colitis. Am J Surg Pathol 2004; 28:999-1006. [PMID: 15252305 DOI: 10.1097/01.pas.0000126758.35603.8d] [Citation(s) in RCA: 51] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Inflammation of ileal reservoir mucosa ("pouchitis") is a common sequelae in ulcerative colitis (UC) patients who have had a colectomy with ileal pouch anal-anastomosis (IPAA). Although several clinical, genetic, and laboratory parameters have been evaluated, reliable pathologic predictors for the development of pouchitis are lacking. The purpose of this case-control study was to determine whether there are any pathologic features in UC colectomy specimens that may help predict the subsequent development of pouchitis after an IPAA procedure. The study group consisted of 39 UC patients (male/female ratio: 21/18, mean age: 35 years), who had at least 1 episode of pouchitis after an IPAA procedure during the follow-up period (mean: 57 months, range: 12-121 months). There were 26 control patients (male/female ratio: 11/15, mean age: 37 years), all of whom also underwent a total colectomy and IPAA procedure for UC, but did not develop pouchitis during the follow-up period (mean: 78 months, range: 14-223 months). Routinely processed tissues from each colectomy specimen were evaluated for a variety of histologic features, such as extent of colitis, severity of colitis, extent of severe colitis, type and extent of ulceration, presence and severity of appendiceal inflammation, and the presence of active ileitis, and compared between the study and control patients. Pathologic features that were associated with the subsequent development of pouchitis included the presence of severe colitis that extended into the cecum (severe pancolitis), which was present in 7/39 (18%) pouchitis patients, but in none (0%) of the control patients (P = 0.03), early fissuring ulcers [9/39 (23%) pouchitis cases versus 1/26 (4%) controls (P = 0.04)], active inflammation of the appendix [20/32 (63%) pouchitis patients versus 7/19 (31%) controls (P = 0.03)], and appendiceal ulceration [13/32 (41%) pouchitis patients versus none (0%) of the controls (P = 0.002)]. No significant differences in patient gender or age, depth or extent of ulceration, or the presence or absence of "backwash ileitis" were identified between the 2 groups. In conclusion, there are several histologic features in colectomy specimens from UC patients who have undergone an IPAA procedure that may help predict the subsequent development of pouchitis. Of these features, appendiceal ulceration is highly associated with pouchitis.
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Affiliation(s)
- Rhonda K Yantiss
- Department of Pathology of the University of Massachusetts Medical School/UMass Memorial Health Care, 55 Lake Avenue North, Worcester, MA 01655, USA.
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Matsumoto T, Jo Y, Mibu R, Hirahashi M, Yao T, Iida M. Multiple microcarcinoids in a patient with long standing ulcerative colitis. J Clin Pathol 2003; 56:963-5. [PMID: 14645360 PMCID: PMC1770128 DOI: 10.1136/jcp.56.12.963] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/11/2003] [Indexed: 12/20/2022]
Abstract
A male patient with a 17 year history of intractable ulcerative colitis of the entire type was treated by total proctocolectomy. Colonoscopy before surgery did not identify dysplasia. Histological examination of the resected colorectum revealed that, in addition to chronic inflammatory infiltrates, there were 21 areas of microcarcinoids located in the muscularis propria and in the superficial layer of the submucosa. Carcinoids may be more common than previously thought, and they may be a reactive phenomenon to a variety of factors in ulcerative colitis.
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Affiliation(s)
- T Matsumoto
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan.
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