Prevention of Post-operative Crohn’s disease recurrence; beyond medications
Main Article Content
Abstract
Historically up to 80% of Crohn’s disease patients required at least one surgical resection in their lifetime. Current ‘treat to target’ management and a burgeoning availability and variety of agents beyond anti-tumour necrosis factor alpha drugs aim to delay and/or reduce the rates of surgery in Crohn’s disease. However, surgery continues to be necessary for many. Even more difficult for patients is the need for repeated surgery with the impact this has on their daily life as well as the increasing risk of stoma and nutritional deficiencies with each operation. Despite the use of biologics, immunomodulators and antibiotics post-operative recurrence is common leading to re-operation in about a third of patients at 10 years from the first operation. Therefore, new approaches are required. Predicting which patients will develop recurrence using genetic and microbiome markers is one approach. Choosing surgical techniques that reduce recurrence rates is another and finally dietary approaches to manipulate the microbiome to reduce recurrence are another potential avenue. We review the literature on postoperative recurrence rates as well as the evidence for these alternative approaches. The aim is to be able to reduce recurrence rates whilst accurately predicting which patients will have disease recurrence with the ultimate goal of a more personalised preventive approach.
Keywords:
Crohn’s disease, postoperative recurrence, genetics, gut microbiome
Article Details
How to Cite
JAVED, Asima; COONEY, Rachel Margaret.
Prevention of Post-operative Crohn’s disease recurrence; beyond medications.
Medical Research Archives, [S.l.], v. 11, n. 7.2, july 2023.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/3928>. Date accessed: 21 nov. 2024.
doi: https://doi.org/10.18103/mra.v11i7.2.3928.
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. Crohn BB. Landmark article Oct 15, 1932. Regional ileitis. A pathological and clinical entity. By Burril B. Crohn, Leon Ginzburg, and Gordon D. Oppenheimer. JAMA: The Journal of the American Medical Association. 1984; 251(1):73-79. doi:10.1001/jama.251.1.73
2. Turner D, Ricciuto A, Lewis A, et al. STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): Determining Therapeutic Goals for Treat-to-Target strategies in IBD. Gastroenterology. 2021;160(5):1570-1583. doi:10.1053/j.gastro.2020.12.031
3. Bemelman WA, Warusavitarne J, Sampietro GM, et al. ECCO-ESCP Consensus on Surgery for Crohn’s Disease. J Crohns Colitis. Published online May 11, 2017. doi:10.1093/ecco-jcc/jjx061
4. Ponsioen CY, de Groof EJ, Eshuis EJ, et al. Laparoscopic ileocaecal resection versus infliximab for terminal ileitis in Crohn’s disease: a randomised controlled, open-label, multicentre trial. Lancet Gastroenterol Hepatol. 2017;2(11):785-792. doi:10.1016/S2468-1253(17)30248-0
5. Kalman TD, Everhov ÅH, Nordenvall C, et al. Decrease in primary but not in secondary abdominal surgery for Crohn’s disease: nationwide cohort study, 1990–2014. British Journal of Surgery. 2020;107(11):1529-1538. doi:10.1002/bjs.11659
6. Rutgeerts P, Geboes K, Vantrappen G, Beyls J, Kerremans R, Hiele M. Predictability of the of Crohn’s Disease Postoperative Course.; 1990.
7. Rutgeerts P, Geboes K, Vantrappen G, Kerremans R, Coenegrachts JL, Coremans G. Natural history of recurrent Crohn’s disease at the ileocolonic anastomosis after curative surgery. Gut. 1984;25(6):665-672. doi:10.1136/gut.25.6.665
8. Olaison G, Smedh K, Sjödahl R. Natural course of Crohn’s disease after ileocolic resection: Endoscopically visualised ileal ulcers preceeding symptoms. Gut. 1992; 33(3):331-335. doi:10.1136/gut.33.3.331
9. Buisson A, Chevaux JB, Allen PB, Bommelaer G, Peyrin-Biroulet L. Review article: the natural history of postoperative Crohn’s disease recurrence. Aliment Pharmacol Ther. 2012;35(6):625-633. doi:10.1111/j.1365-2036.2012.05002.x
10. Bernell O, Lapidus A, Hellers G. Risk Factors for Surgery and Postoperative Recurrence in Crohn’s Disease. Ann Surg. 2000;231(1):38. doi:10.1097/00000658-200001000-00006
11. Cunningham MF, Docherty NG, Coffey JC, Burke JP, O’Connell PR. Postsurgical Recurrence of Ileal Crohn’s Disease: An Update on Risk Factors and Intervention Points to a Central Role for Impaired Host-Microflora Homeostasis. World J Surg. 2010;34(7):1615-1626. doi:10.1007/s00268-010-0504-6
12. Tsai L, Ma C, Dulai PS, et al. Contemporary Risk of Surgery in Patients With Ulcerative Colitis and Crohn’s Disease: A Meta-Analysis of Population-Based Cohorts. Clinical Gastroenterology and Hepatology. 2021;19(10):2031-2045.e11. doi:10.1016/j.cgh.2020.10.039
13. Frolkis AD, Lipton DS, Fiest KM, et al. Cumulative Incidence of Second Intestinal Resection in Crohn’s Disease: A Systematic Review and Meta-Analysis of Population-Based Studies. American Journal of Gastroenterology. 2014;109(11):1739-1748. doi:10.1038/ajg.2014.297
14. Lamb CA, Kennedy NA, Raine T, et al. British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults. Gut. 2019;68(Suppl 3):s1-s106. doi:10.1136/gutjnl-2019-318484
15. Auzolle C, Nancey S, Tran-Minh ML, et al. Male gender, active smoking and previous intestinal resection are risk factors for post-operative endoscopic recurrence in Crohn’s disease: results from a prospective cohort study. Aliment Pharmacol Ther. 2018; 48(9):924-932. doi:10.1111/apt.14944
16. Gionchetti P, Dignass A, Danese S, et al. 3rd European Evidence-based Consensus on the Diagnosis and Management of Crohn’s Disease 2016: Part 2: Surgical Management and Special Situations. J Crohns Colitis. 2017; 11(2):135-149. doi:10.1093/ecco-jcc/jjw169
17. PASCUA M, SU C, LEWIS JD, BRENSINGER C, LICHTENSTEIN GR. Meta-analysis: factors predicting post-operative recurrence with placebo therapy in patients with Crohn’s disease. Aliment Pharmacol Ther. 2008;28(5):545-556. doi:10.1111/j.1365-2036.2008.03774.x
18. Simillis C, Jacovides M, Reese GE, Yamamoto T, Tekkis PP. Meta-analysis of the Role of Granulomas in the Recurrence of Crohn Disease. Dis Colon Rectum. 2010;53(2): 177-185. doi:10.1007/DCR.0b013e3181b7bfb0
19. Ferrante M, de Hertogh G, Hlavaty T, et al. The Value of Myenteric Plexitis to Predict Early Postoperative Crohn’s Disease Recurrence. Gastroenterology. 2006;130(6): 1595-1606. doi:10.1053/j.gastro.2006.02.025
20. Mowat C, Arnott I, Cahill A, et al. Mercaptopurine versus placebo to prevent recurrence of Crohn’s disease after surgical resection (TOPPIC): a multicentre, double-blind, randomised controlled trial. Lancet Gastroenterol Hepatol. 2016;1(4):273-282. doi:10.1016/S2468-1253(16)30078-4
21. de Cruz P, Kamm MA, Hamilton AL, et al. Crohn’s disease management after intestinal resection: a randomised trial. The Lancet. 2015;385(9976):1406-1417. doi:10.1016/S0140-6736(14)61908-5
22. Jain SR, Ow ZGW, Chin YH, et al. Quantifying the rate of recurrence ofpostoperative Crohn’s disease with biological therapy. A meta‐analysis . J Dig Dis. 2021;22(7):399-407. doi:10.1111/1751-2980.13025
23. National Institute for Health and Care Excellence (Great Britain), National Guideline Centre (Great Britain). Crohn’s Disease : Management.
24. Verstockt S, Machiels K, Dehairs J, et al. OP01 Sequencing-based gene network analysis reveals a profound role for ferroptosis key gene GPX4 in post-operative endoscopic recurrence in Crohn’s disease. J Crohns Colitis. 2023;17(Supplement_1):i1-i3. doi:10.1093/ecco-jcc/jjac190.0001
25. Adamina M, Bonovas S, Raine T, et al. ECCO Guidelines on Therapeutics in Crohn’s Disease: Surgical Treatment. J Crohns Colitis. 2020;14(2):155-168. doi:10.1093/ecco-jcc/jjz187
26. He X, Chen Z, Huang J, et al. Stapled Side-to-Side Anastomosis Might Be Better Than Handsewn End-to-End Anastomosis in Ileocolic Resection for Crohn’s Disease: A Meta-Analysis. Dig Dis Sci. 2014;59(7):1544-1551. doi:10.1007/s10620-014-3039-0
27. Feng J shan, Li J yu, Yang Z, Chen X yan, Mo J jie, Li S hai. Stapled side-to-side anastomosis might be benefit in intestinal resection for Crohn’s disease. Medicine. 2018; 97(15):e0315. doi:10.1097/MD.0000000000010315
28. Sensi B, Siragusa L, Efrati C, et al. The Role of Inflammation in Crohn’s Disease Recurrence after Surgical Treatment. J Immunol Res. 2020;2020:1-14. doi:10.1155/2020/8846982
29. CAMERON JL, HAMILTON SR, COLEMAN J, SITZMANN J v., BAYLESS TM. Patterns of Heal Recurrence in Crohnʼs Disease. Ann Surg. 1992;215(5):546. doi:10.1097/00000658-199205000-00018
30. Bakkevold KE. Construction of an ileocolic neosphincter — Nipple valve anastomosis for prevention of postoperative recurrence of Crohn’s disease in the neoterminal ileum after ileocecal or ileocolic resection. J Crohns Colitis. 2009;3(3):183-188. doi:10.1016/j.crohns.2009.04.002
31. Smedh K, Olaison G, Sjödahl R. Ileocolic nipple valve anastomosis for preventing recurrence of surgically treated Crohn’s disease. Dis Colon Rectum. 1990;33(11):987-990. doi:10.1007/BF02139113
32. Kono T, Ashida T, Ebisawa Y, et al. A New Antimesenteric Functional End-to-End Handsewn Anastomosis: Surgical Prevention of Anastomotic Recurrence in Crohn’s Disease. Dis Colon Rectum. 2011;54(5):586-592. doi:10.1007/DCR.0b013e318208b90f
33. Shimada N, Ohge H, Kono T, et al. Surgical Recurrence at Anastomotic Site After Bowel Resection in Crohn’s Disease: Comparison of Kono-S and End-to-end Anastomosis. Journal of Gastrointestinal Surgery. 2019;23(2):312-319. doi:10.1007/s11605-018-4012-6
34. Kono T, Fichera A, Maeda K, et al. Kono-S Anastomosis for Surgical Prophylaxis of Anastomotic Recurrence in Crohn’s Disease: an International Multicenter Study. Journal of Gastrointestinal Surgery. 2016;20(4):783-790. doi:10.1007/s11605-015-3061-3
35. Katsuno H, Maeda K, Hanai T, Masumori K, Koide Y, Kono T. Novel Antimesenteric Functional End-to-End Handsewn (Kono-S) Anastomoses for Crohn’s Disease: A Report of Surgical Procedure and Short-Term Outcomes. Dig Surg. 2015;32(1):39-44. doi:10.1159/000371857
36. Fichera A, Zoccali M, Kono T. Antimesenteric Functional End-to-End Handsewn (Kono-S) Anastomosis. Journal of Gastrointestinal Surgery. 2012;16(7):1412-1416. doi:10.1007/s11605-012-1905-7
37. Luglio G, Rispo A, Imperatore N, et al. Surgical Prevention of Anastomotic Recurrence by Excluding Mesentery in Crohn’s Disease: The SuPREMe-CD Study - A Randomized Clinical Trial. Ann Surg. 2020; 272(2):210-217. doi:10.1097/SLA.0000000000003821
38. Rivera ED, Coffey JC, Walsh D, Ehrenpreis ED. The Mesentery, Systemic Inflammation, and Crohn’s Disease. Inflamm Bowel Dis. 2019;25(2):226-234. doi:10.1093/ibd/izy201
39. Coffey JC, O‘Leary DP, Kiernan MG, Faul P. The mesentery in Crohn’s disease. Curr Opin Gastroenterol. 2016;32(4):267-273. doi:10.1097/MOG.0000000000000280
40. Randolph GJ, Bala S, Rahier JF, et al. Lymphoid Aggregates Remodel Lymphatic Collecting Vessels that Serve Mesenteric Lymph Nodes in Crohn Disease. Am J Pathol. 2016;186(12):3066-3073. doi:10.1016/j.ajpath.2016.07.026
41. Peyrin-Biroulet L, Gonzalez F, Dubuquoy L, et al. Mesenteric fat as a source of C reactive protein and as a target for bacterial translocation in Crohn’s disease. Gut. 2012; 61(1):78-85. doi:10.1136/gutjnl-2011-300370
42. Coffey CJ, Kiernan MG, Sahebally SM, et al. Inclusion of the Mesentery in Ileocolic Resection for Crohn’s Disease is Associated With Reduced Surgical Recurrence. J Crohns Colitis. 2018;12(10):1139-1150. doi:10.1093/ecco-jcc/jjx187
43. Buskens CJ, Bemelman WA. Inclusion of the Mesentery in Ileocolic Resection for Crohn’s Disease is Associated with Reduced Surgical Recurrence. J Crohns Colitis. 2018;12 (10):1137-1138. doi:10.1093/ecco-jcc/jjy115
44. Gerasimidis K, Godny L, Sigall-Boneh R, Svolos V, Wall C, Halmos E. Current recommendations on the role of diet in the aetiology and management of IBD. Frontline Gastroenterol. 2022;13(2):160-167. doi:10.1136/flgastro-2020-101429
45. Day AS, Lopez RN. Exclusive enteral nutrition in children with Crohn’s disease. World J Gastroenterol. 2015;21(22):6809-6816. doi:10.3748/wjg.v21.i22.6809
46. Zachos M, Tondeur M, Griffiths AM. Enteral nutritional therapy for induction of remission in Crohn’s disease. Cochrane Database of Systematic Reviews. Published online January 24, 2007. doi:10.1002/14651858.CD000542.pub2
47. Shariff S, Moran G, Grimes C, Cooney RM. Current Use of EEN in Pre-Operative Optimisation in Crohn’s Disease. Nutrients. 2021;13(12):4389. doi:10.3390/nu13124389
48. Adamina M, Gerasimidis K, Sigall-Boneh R, et al. Perioperative Dietary Therapy in Inflammatory Bowel Disease. J Crohns Colitis. 2020;14(4):431-444. doi:10.1093/ecco-jcc/jjz160
49. Wang H, Zuo L, Zhao J, et al. Impact of Preoperative Exclusive Enteral Nutrition on Postoperative Complications and Recurrence After Bowel Resection in Patients with Active Crohn’s Disease. World J Surg. 2016;40(8): 1993-2000. doi:10.1007/s00268-016-3488-z
50. Ge X, Tang S, Yang X, et al. The role of exclusive enteral nutrition in the preoperative optimization of laparoscopic surgery for patients with Crohn’s disease: A cohort study. International Journal of Surgery. 2019;65:39-44. doi:10.1016/j.ijsu.2019.03.012
51. YAMAMOTO T, NAKAHIGASHI M, UMEGAE S, KITAGAWA T, MATSUMOTO K. Impact of long-term enteral nutrition on clinical and endoscopic recurrence after resection for Crohn’s disease: a prospective, non-randomized, parallel, controlled study. Aliment Pharmacol Ther. 2006;25(1):67-72. doi:10.1111/j.1365-2036.2006.03158.x
52. Yamamoto T, Shiraki M, Nakahigashi M, Umegae S, Matsumoto K. Enteral nutrition to suppress postoperative Crohn’s disease recurrence: a five-year prospective cohort study. Int J Colorectal Dis. 2013;28(3):335-340. doi:10.1007/s00384-012-1587-3
53. Khalili H, Håkansson N, Chan SS, et al. Adherence to a Mediterranean diet is associated with a lower risk of later-onset Crohn’s disease: results from two large prospective cohort studies. Gut. 2020;69(9): 1637-1644. doi:10.1136/gutjnl-2019-319505
54. Lo CH, Lochhead P, Khalili H, et al. Dietary Inflammatory Potential and Risk of Crohn’s Disease and Ulcerative Colitis. Gastroenterology. 2020;159(3):873-883.e1. doi:10.1053/j.gastro.2020.05.011
55. Yanai H, Levine A, Hirsch A, et al. The Crohn’s disease exclusion diet for induction and maintenance of remission in adults with mild-to-moderate Crohn’s disease (CDED-AD): an open-label, pilot, randomised trial. Lancet Gastroenterol Hepatol. 2022;7(1):49-59. doi:10.1016/S2468-1253(21)00299-5
56. Ruemmele FM. Role of Diet in Inflammatory Bowel Disease. Ann Nutr Metab. 2016;68(Suppl. 1):32-41. doi:10.1159/000445392
57. MacLellan A, Connors J, Grant S, Cahill L, Langille M, van Limbergen J. The Impact of Exclusive Enteral Nutrition (EEN) on the Gut Microbiome in Crohn’s Disease: A Review. Nutrients. 2017;9(5):0447. doi:10.3390/nu9050447
58. Caruso R, Lo BC, Núñez G. Host–microbiota interactions in inflammatory bowel disease. Nat Rev Immunol. 2020;20(7):411-426. doi:10.1038/s41577-019-0268-7
59. di Sario A, Sassaroli P, Daretti L, et al. Postoperative Recurrence of Crohn’s Disease: Pathophysiology, Diagnosis and Treatment. Curr Pharm Biotechnol. 2018;18(12):979-988. doi:10.2174/1389201019666180216152805
60. Lloyd-Price J, Arze C, Ananthakrishnan AN, et al. Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases. Nature. 2019;569(7758):655-662. doi:10.1038/s41586-019-1237-9
61. de Cruz P, Kang S, Wagner J, et al. Association between specific mucosa-associated microbiota in Crohn’s disease at the time of resection and subsequent disease recurrence: A pilot study. J Gastroenterol Hepatol. 2015;30(2):268-278. doi:10.1111/jgh.12694
62. Wright EK, Kamm MA, Wagner J, et al. Microbial Factors Associated with Postoperative Crohn’s Disease Recurrence. J Crohns Colitis. 2017;11(2):191-203. doi:10.1093/ecco-jcc/jjw136
63. Strömbeck A, Lasson A, Strid H, et al. Fecal microbiota composition is linked to the postoperative disease course in patients with Crohn’s disease. BMC Gastroenterol. 2020; 20(1):130. doi:10.1186/s12876-020-01281-4
64. Hamilton AL, Kamm MA, de Cruz P, et al. Luminal microbiota related to Crohn’s disease recurrence after surgery. Gut Microbes. 2020;11(6):1713-1728. doi:10.1080/19490976.2020.1778262
65. Dey N, Soergel DA, Repo S, Brenner SE. Association of gut microbiota with post-operative clinical course in Crohn’s disease. BMC Gastroenterol. 2013;13(1):131. doi:10.1186/1471-230X-13-131
66. Machiels K, Pozuelo del Río M, Martinez-De la Torre A, et al. Early Postoperative Endoscopic Recurrence in Crohn’s Disease Is Characterised by Distinct Microbiota Recolonisation. J Crohns Colitis. 2020;14(11): 1535-1546. doi:10.1093/ecco-jcc/jjaa081
67. Keshteli AH, Tso R, Dieleman LA, et al. A Distinctive Urinary Metabolomic Fingerprint Is Linked With Endoscopic Postoperative Disease Recurrence in Crohn’s Disease Patients. Inflamm Bowel Dis. 2018;24(4):861-870. doi:10.1093/ibd/izx070
68. Zhuang X, Tian Z, Li N, et al. Gut Microbiota Profiles and Microbial-Based Therapies in Post-operative Crohn’s Disease: A Systematic Review. Front Med (Lausanne). 2021;7. doi:10.3389/fmed.2020.615858
69. Rutgeerts P, Hiele M, Geboes K, et al. Controlled trial of metronidazole treatment for prevention of crohn’s recurrence after ileal resection. Gastroenterology. 1995;108(6): 1617-1621. doi:10.1016/0016-5085(95)90121-3
70. Rutgeerts P, van Assche G, Vermeire S, et al. Ornidazole for prophylaxis of postoperative Crohn’s disease recurrence: A randomized, double-blind, placebo-controlled trial. Gastroenterology. 2005;128 (4):856-861. doi:10.1053/j.gastro.2005.01.010
71. Herfarth HH, Katz JA, Hanauer SB, et al. Ciprofloxacin for the Prevention of Postoperative Recurrence in Patients with Crohnʼs Disease. Inflamm Bowel Dis. 2013; 19(5):1073-1079. doi:10.1097/01.MIB.0000428910.36091.10
72. Campieri M, Rizzello F, Venturi A, Poggioli G, Ugolini F. Combination of antibiotic and probiotic treatment is efficacious in prophylaxis of post-operative recurrence of Crohn’s disease: A randomized controlled study VS mesalamine. Gastroenterology. 2000;118(4): A781. doi:10.1016/S0016-5085(00)85267-1
73. Marteau P. Ineffectiveness of Lactobacillus johnsonii LA1 for prophylaxis of postoperative recurrence in Crohn’s disease: a randomised, double blind, placebo controlled GETAID trial. Gut. 2006;55(6):842-847. doi:10.1136/gut.2005.076604
74. van Gossum A, Dewit O, Louis E, et al. Multicenter randomized-controlled clinical trial of probiotics (Lactobacillus johnsonii, LA1) on early endoscopic recurrence of Crohnʼs disease after ileo-caecal resection. Inflamm Bowel Dis. 2007;13(2):135-142. doi:10.1002/ibd.20063
75. Fedorak RN, Feagan BG, Hotte N, et al. The Probiotic VSL#3 Has Anti-inflammatory Effects and Could Reduce Endoscopic Recurrence After Surgery for Crohn’s Disease. Clinical Gastroenterology and Hepatology. 2015;13(5):928-935.e2. doi:10.1016/j.cgh.2014.10.031
76. Chermesh I, Tamir A, Reshef R, et al. Failure of Synbiotic 2000 to Prevent Postoperative Recurrence of Crohn’s Disease. Dig Dis Sci. 2007;52(2):385-389. doi:10.1007/s10620-006-9549-7
77. Liu JZ, Anderson CA. Genetic studies of Crohn’s disease: Past, present and future. Best Pract Res Clin Gastroenterol. 2014;28(3): 373-386. doi:10.1016/j.bpg.2014.04.009
78. Jostins L, Ripke S, Weersma RK, et al. Host–microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature. 2012;491(7422):119-124. doi:10.1038/nature11582
79. Cleynen I, González JR, Figueroa C, et al. Genetic factors conferring an increased susceptibility to develop Crohn’s disease also influence disease phenotype: results from the IBDchip European Project. Gut. 2013;62(11): 1556-1565. doi:10.1136/gutjnl-2011-300777
80. Sidiq T, Yoshihama S, Downs I, Kobayashi KS. Nod2: A Critical Regulator of Ileal Microbiota and Crohn’s Disease. Front Immunol. 2016;7. doi:10.3389/fimmu.2016.00367
81. Büning C, Genschel J, Bühner S, et al. Mutations in the NOD2/CARD15 gene in Crohn’s disease are associated with ileocecal resection and are a risk factor for reoperation. Aliment Pharmacol Ther. 2004;19(10):1073-1078. doi:10.1111/j.1365-2036.2004.01967.x
82. Bhullar M. Prediction of Crohn’s disease aggression through NOD2 / CARD15 gene sequencing in an Australian cohort. World J Gastroenterol. 2014;20(17):5008. doi:10.3748/wjg.v20.i17.5008
83. Maconi G, Colombo E, Sampietro GM, et al. CARD15 Gene Variants and Risk of Reoperation in Crohn’s Disease Patients. Am J Gastroenterol. 2009;104(10):2483-2491. doi:10.1038/ajg.2009.413
84. Dang JT, Dang TT, Wine E, Dicken B, Madsen K, Laffin M. The Genetics of Postoperative Recurrence in Crohn Disease: A Systematic Review, Meta-analysis, and Framework for Future Work. Crohns Colitis 360. 2021;3(2). doi:10.1093/crocol/otaa094
85. Sehgal R, Berg A, Polinski JI, et al. Mutations in IRGM Are Associated With More Frequent Need for Surgery in Patients With Ileocolonic Crohn’s Disease. Dis Colon Rectum. 2012;55(2):115-121. doi:10.1097/DCR.0b013e31823ccea8
86. Germain A, Guéant RM, Chamaillard M, Bresler L, Guéant JL, Peyrin-Biroulet L. CARD8 gene variant is a risk factor for recurrent surgery in patients with Crohn’s disease. Digestive and Liver Disease. 2015;47(11):938-942. doi:10.1016/j.dld.2015.07.013
87. Gerich ME, Fleshner P, Panikkath D, et al. Mo1299 Genotype and Post-Operative Immunosuppression Impact Surgical Recurrence in Crohn’s Disease. Gastroenterology. 2013; 144(5):S-630. doi:10.1016/S0016-5085(13)62332-X
88. Laffin MR, Fedorak RN, Wine E, Dicken B, Madsen KL. A BACH2 Gene Variant Is Associated with Postoperative Recurrence of Crohn’s Disease. J Am Coll Surg. 2018;226(5): 902-908. doi:10.1016/j.jamcollsurg.2018.01.052
2. Turner D, Ricciuto A, Lewis A, et al. STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): Determining Therapeutic Goals for Treat-to-Target strategies in IBD. Gastroenterology. 2021;160(5):1570-1583. doi:10.1053/j.gastro.2020.12.031
3. Bemelman WA, Warusavitarne J, Sampietro GM, et al. ECCO-ESCP Consensus on Surgery for Crohn’s Disease. J Crohns Colitis. Published online May 11, 2017. doi:10.1093/ecco-jcc/jjx061
4. Ponsioen CY, de Groof EJ, Eshuis EJ, et al. Laparoscopic ileocaecal resection versus infliximab for terminal ileitis in Crohn’s disease: a randomised controlled, open-label, multicentre trial. Lancet Gastroenterol Hepatol. 2017;2(11):785-792. doi:10.1016/S2468-1253(17)30248-0
5. Kalman TD, Everhov ÅH, Nordenvall C, et al. Decrease in primary but not in secondary abdominal surgery for Crohn’s disease: nationwide cohort study, 1990–2014. British Journal of Surgery. 2020;107(11):1529-1538. doi:10.1002/bjs.11659
6. Rutgeerts P, Geboes K, Vantrappen G, Beyls J, Kerremans R, Hiele M. Predictability of the of Crohn’s Disease Postoperative Course.; 1990.
7. Rutgeerts P, Geboes K, Vantrappen G, Kerremans R, Coenegrachts JL, Coremans G. Natural history of recurrent Crohn’s disease at the ileocolonic anastomosis after curative surgery. Gut. 1984;25(6):665-672. doi:10.1136/gut.25.6.665
8. Olaison G, Smedh K, Sjödahl R. Natural course of Crohn’s disease after ileocolic resection: Endoscopically visualised ileal ulcers preceeding symptoms. Gut. 1992; 33(3):331-335. doi:10.1136/gut.33.3.331
9. Buisson A, Chevaux JB, Allen PB, Bommelaer G, Peyrin-Biroulet L. Review article: the natural history of postoperative Crohn’s disease recurrence. Aliment Pharmacol Ther. 2012;35(6):625-633. doi:10.1111/j.1365-2036.2012.05002.x
10. Bernell O, Lapidus A, Hellers G. Risk Factors for Surgery and Postoperative Recurrence in Crohn’s Disease. Ann Surg. 2000;231(1):38. doi:10.1097/00000658-200001000-00006
11. Cunningham MF, Docherty NG, Coffey JC, Burke JP, O’Connell PR. Postsurgical Recurrence of Ileal Crohn’s Disease: An Update on Risk Factors and Intervention Points to a Central Role for Impaired Host-Microflora Homeostasis. World J Surg. 2010;34(7):1615-1626. doi:10.1007/s00268-010-0504-6
12. Tsai L, Ma C, Dulai PS, et al. Contemporary Risk of Surgery in Patients With Ulcerative Colitis and Crohn’s Disease: A Meta-Analysis of Population-Based Cohorts. Clinical Gastroenterology and Hepatology. 2021;19(10):2031-2045.e11. doi:10.1016/j.cgh.2020.10.039
13. Frolkis AD, Lipton DS, Fiest KM, et al. Cumulative Incidence of Second Intestinal Resection in Crohn’s Disease: A Systematic Review and Meta-Analysis of Population-Based Studies. American Journal of Gastroenterology. 2014;109(11):1739-1748. doi:10.1038/ajg.2014.297
14. Lamb CA, Kennedy NA, Raine T, et al. British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults. Gut. 2019;68(Suppl 3):s1-s106. doi:10.1136/gutjnl-2019-318484
15. Auzolle C, Nancey S, Tran-Minh ML, et al. Male gender, active smoking and previous intestinal resection are risk factors for post-operative endoscopic recurrence in Crohn’s disease: results from a prospective cohort study. Aliment Pharmacol Ther. 2018; 48(9):924-932. doi:10.1111/apt.14944
16. Gionchetti P, Dignass A, Danese S, et al. 3rd European Evidence-based Consensus on the Diagnosis and Management of Crohn’s Disease 2016: Part 2: Surgical Management and Special Situations. J Crohns Colitis. 2017; 11(2):135-149. doi:10.1093/ecco-jcc/jjw169
17. PASCUA M, SU C, LEWIS JD, BRENSINGER C, LICHTENSTEIN GR. Meta-analysis: factors predicting post-operative recurrence with placebo therapy in patients with Crohn’s disease. Aliment Pharmacol Ther. 2008;28(5):545-556. doi:10.1111/j.1365-2036.2008.03774.x
18. Simillis C, Jacovides M, Reese GE, Yamamoto T, Tekkis PP. Meta-analysis of the Role of Granulomas in the Recurrence of Crohn Disease. Dis Colon Rectum. 2010;53(2): 177-185. doi:10.1007/DCR.0b013e3181b7bfb0
19. Ferrante M, de Hertogh G, Hlavaty T, et al. The Value of Myenteric Plexitis to Predict Early Postoperative Crohn’s Disease Recurrence. Gastroenterology. 2006;130(6): 1595-1606. doi:10.1053/j.gastro.2006.02.025
20. Mowat C, Arnott I, Cahill A, et al. Mercaptopurine versus placebo to prevent recurrence of Crohn’s disease after surgical resection (TOPPIC): a multicentre, double-blind, randomised controlled trial. Lancet Gastroenterol Hepatol. 2016;1(4):273-282. doi:10.1016/S2468-1253(16)30078-4
21. de Cruz P, Kamm MA, Hamilton AL, et al. Crohn’s disease management after intestinal resection: a randomised trial. The Lancet. 2015;385(9976):1406-1417. doi:10.1016/S0140-6736(14)61908-5
22. Jain SR, Ow ZGW, Chin YH, et al. Quantifying the rate of recurrence of
23. National Institute for Health and Care Excellence (Great Britain), National Guideline Centre (Great Britain). Crohn’s Disease : Management.
24. Verstockt S, Machiels K, Dehairs J, et al. OP01 Sequencing-based gene network analysis reveals a profound role for ferroptosis key gene GPX4 in post-operative endoscopic recurrence in Crohn’s disease. J Crohns Colitis. 2023;17(Supplement_1):i1-i3. doi:10.1093/ecco-jcc/jjac190.0001
25. Adamina M, Bonovas S, Raine T, et al. ECCO Guidelines on Therapeutics in Crohn’s Disease: Surgical Treatment. J Crohns Colitis. 2020;14(2):155-168. doi:10.1093/ecco-jcc/jjz187
26. He X, Chen Z, Huang J, et al. Stapled Side-to-Side Anastomosis Might Be Better Than Handsewn End-to-End Anastomosis in Ileocolic Resection for Crohn’s Disease: A Meta-Analysis. Dig Dis Sci. 2014;59(7):1544-1551. doi:10.1007/s10620-014-3039-0
27. Feng J shan, Li J yu, Yang Z, Chen X yan, Mo J jie, Li S hai. Stapled side-to-side anastomosis might be benefit in intestinal resection for Crohn’s disease. Medicine. 2018; 97(15):e0315. doi:10.1097/MD.0000000000010315
28. Sensi B, Siragusa L, Efrati C, et al. The Role of Inflammation in Crohn’s Disease Recurrence after Surgical Treatment. J Immunol Res. 2020;2020:1-14. doi:10.1155/2020/8846982
29. CAMERON JL, HAMILTON SR, COLEMAN J, SITZMANN J v., BAYLESS TM. Patterns of Heal Recurrence in Crohnʼs Disease. Ann Surg. 1992;215(5):546. doi:10.1097/00000658-199205000-00018
30. Bakkevold KE. Construction of an ileocolic neosphincter — Nipple valve anastomosis for prevention of postoperative recurrence of Crohn’s disease in the neoterminal ileum after ileocecal or ileocolic resection. J Crohns Colitis. 2009;3(3):183-188. doi:10.1016/j.crohns.2009.04.002
31. Smedh K, Olaison G, Sjödahl R. Ileocolic nipple valve anastomosis for preventing recurrence of surgically treated Crohn’s disease. Dis Colon Rectum. 1990;33(11):987-990. doi:10.1007/BF02139113
32. Kono T, Ashida T, Ebisawa Y, et al. A New Antimesenteric Functional End-to-End Handsewn Anastomosis: Surgical Prevention of Anastomotic Recurrence in Crohn’s Disease. Dis Colon Rectum. 2011;54(5):586-592. doi:10.1007/DCR.0b013e318208b90f
33. Shimada N, Ohge H, Kono T, et al. Surgical Recurrence at Anastomotic Site After Bowel Resection in Crohn’s Disease: Comparison of Kono-S and End-to-end Anastomosis. Journal of Gastrointestinal Surgery. 2019;23(2):312-319. doi:10.1007/s11605-018-4012-6
34. Kono T, Fichera A, Maeda K, et al. Kono-S Anastomosis for Surgical Prophylaxis of Anastomotic Recurrence in Crohn’s Disease: an International Multicenter Study. Journal of Gastrointestinal Surgery. 2016;20(4):783-790. doi:10.1007/s11605-015-3061-3
35. Katsuno H, Maeda K, Hanai T, Masumori K, Koide Y, Kono T. Novel Antimesenteric Functional End-to-End Handsewn (Kono-S) Anastomoses for Crohn’s Disease: A Report of Surgical Procedure and Short-Term Outcomes. Dig Surg. 2015;32(1):39-44. doi:10.1159/000371857
36. Fichera A, Zoccali M, Kono T. Antimesenteric Functional End-to-End Handsewn (Kono-S) Anastomosis. Journal of Gastrointestinal Surgery. 2012;16(7):1412-1416. doi:10.1007/s11605-012-1905-7
37. Luglio G, Rispo A, Imperatore N, et al. Surgical Prevention of Anastomotic Recurrence by Excluding Mesentery in Crohn’s Disease: The SuPREMe-CD Study - A Randomized Clinical Trial. Ann Surg. 2020; 272(2):210-217. doi:10.1097/SLA.0000000000003821
38. Rivera ED, Coffey JC, Walsh D, Ehrenpreis ED. The Mesentery, Systemic Inflammation, and Crohn’s Disease. Inflamm Bowel Dis. 2019;25(2):226-234. doi:10.1093/ibd/izy201
39. Coffey JC, O‘Leary DP, Kiernan MG, Faul P. The mesentery in Crohn’s disease. Curr Opin Gastroenterol. 2016;32(4):267-273. doi:10.1097/MOG.0000000000000280
40. Randolph GJ, Bala S, Rahier JF, et al. Lymphoid Aggregates Remodel Lymphatic Collecting Vessels that Serve Mesenteric Lymph Nodes in Crohn Disease. Am J Pathol. 2016;186(12):3066-3073. doi:10.1016/j.ajpath.2016.07.026
41. Peyrin-Biroulet L, Gonzalez F, Dubuquoy L, et al. Mesenteric fat as a source of C reactive protein and as a target for bacterial translocation in Crohn’s disease. Gut. 2012; 61(1):78-85. doi:10.1136/gutjnl-2011-300370
42. Coffey CJ, Kiernan MG, Sahebally SM, et al. Inclusion of the Mesentery in Ileocolic Resection for Crohn’s Disease is Associated With Reduced Surgical Recurrence. J Crohns Colitis. 2018;12(10):1139-1150. doi:10.1093/ecco-jcc/jjx187
43. Buskens CJ, Bemelman WA. Inclusion of the Mesentery in Ileocolic Resection for Crohn’s Disease is Associated with Reduced Surgical Recurrence. J Crohns Colitis. 2018;12 (10):1137-1138. doi:10.1093/ecco-jcc/jjy115
44. Gerasimidis K, Godny L, Sigall-Boneh R, Svolos V, Wall C, Halmos E. Current recommendations on the role of diet in the aetiology and management of IBD. Frontline Gastroenterol. 2022;13(2):160-167. doi:10.1136/flgastro-2020-101429
45. Day AS, Lopez RN. Exclusive enteral nutrition in children with Crohn’s disease. World J Gastroenterol. 2015;21(22):6809-6816. doi:10.3748/wjg.v21.i22.6809
46. Zachos M, Tondeur M, Griffiths AM. Enteral nutritional therapy for induction of remission in Crohn’s disease. Cochrane Database of Systematic Reviews. Published online January 24, 2007. doi:10.1002/14651858.CD000542.pub2
47. Shariff S, Moran G, Grimes C, Cooney RM. Current Use of EEN in Pre-Operative Optimisation in Crohn’s Disease. Nutrients. 2021;13(12):4389. doi:10.3390/nu13124389
48. Adamina M, Gerasimidis K, Sigall-Boneh R, et al. Perioperative Dietary Therapy in Inflammatory Bowel Disease. J Crohns Colitis. 2020;14(4):431-444. doi:10.1093/ecco-jcc/jjz160
49. Wang H, Zuo L, Zhao J, et al. Impact of Preoperative Exclusive Enteral Nutrition on Postoperative Complications and Recurrence After Bowel Resection in Patients with Active Crohn’s Disease. World J Surg. 2016;40(8): 1993-2000. doi:10.1007/s00268-016-3488-z
50. Ge X, Tang S, Yang X, et al. The role of exclusive enteral nutrition in the preoperative optimization of laparoscopic surgery for patients with Crohn’s disease: A cohort study. International Journal of Surgery. 2019;65:39-44. doi:10.1016/j.ijsu.2019.03.012
51. YAMAMOTO T, NAKAHIGASHI M, UMEGAE S, KITAGAWA T, MATSUMOTO K. Impact of long-term enteral nutrition on clinical and endoscopic recurrence after resection for Crohn’s disease: a prospective, non-randomized, parallel, controlled study. Aliment Pharmacol Ther. 2006;25(1):67-72. doi:10.1111/j.1365-2036.2006.03158.x
52. Yamamoto T, Shiraki M, Nakahigashi M, Umegae S, Matsumoto K. Enteral nutrition to suppress postoperative Crohn’s disease recurrence: a five-year prospective cohort study. Int J Colorectal Dis. 2013;28(3):335-340. doi:10.1007/s00384-012-1587-3
53. Khalili H, Håkansson N, Chan SS, et al. Adherence to a Mediterranean diet is associated with a lower risk of later-onset Crohn’s disease: results from two large prospective cohort studies. Gut. 2020;69(9): 1637-1644. doi:10.1136/gutjnl-2019-319505
54. Lo CH, Lochhead P, Khalili H, et al. Dietary Inflammatory Potential and Risk of Crohn’s Disease and Ulcerative Colitis. Gastroenterology. 2020;159(3):873-883.e1. doi:10.1053/j.gastro.2020.05.011
55. Yanai H, Levine A, Hirsch A, et al. The Crohn’s disease exclusion diet for induction and maintenance of remission in adults with mild-to-moderate Crohn’s disease (CDED-AD): an open-label, pilot, randomised trial. Lancet Gastroenterol Hepatol. 2022;7(1):49-59. doi:10.1016/S2468-1253(21)00299-5
56. Ruemmele FM. Role of Diet in Inflammatory Bowel Disease. Ann Nutr Metab. 2016;68(Suppl. 1):32-41. doi:10.1159/000445392
57. MacLellan A, Connors J, Grant S, Cahill L, Langille M, van Limbergen J. The Impact of Exclusive Enteral Nutrition (EEN) on the Gut Microbiome in Crohn’s Disease: A Review. Nutrients. 2017;9(5):0447. doi:10.3390/nu9050447
58. Caruso R, Lo BC, Núñez G. Host–microbiota interactions in inflammatory bowel disease. Nat Rev Immunol. 2020;20(7):411-426. doi:10.1038/s41577-019-0268-7
59. di Sario A, Sassaroli P, Daretti L, et al. Postoperative Recurrence of Crohn’s Disease: Pathophysiology, Diagnosis and Treatment. Curr Pharm Biotechnol. 2018;18(12):979-988. doi:10.2174/1389201019666180216152805
60. Lloyd-Price J, Arze C, Ananthakrishnan AN, et al. Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases. Nature. 2019;569(7758):655-662. doi:10.1038/s41586-019-1237-9
61. de Cruz P, Kang S, Wagner J, et al. Association between specific mucosa-associated microbiota in Crohn’s disease at the time of resection and subsequent disease recurrence: A pilot study. J Gastroenterol Hepatol. 2015;30(2):268-278. doi:10.1111/jgh.12694
62. Wright EK, Kamm MA, Wagner J, et al. Microbial Factors Associated with Postoperative Crohn’s Disease Recurrence. J Crohns Colitis. 2017;11(2):191-203. doi:10.1093/ecco-jcc/jjw136
63. Strömbeck A, Lasson A, Strid H, et al. Fecal microbiota composition is linked to the postoperative disease course in patients with Crohn’s disease. BMC Gastroenterol. 2020; 20(1):130. doi:10.1186/s12876-020-01281-4
64. Hamilton AL, Kamm MA, de Cruz P, et al. Luminal microbiota related to Crohn’s disease recurrence after surgery. Gut Microbes. 2020;11(6):1713-1728. doi:10.1080/19490976.2020.1778262
65. Dey N, Soergel DA, Repo S, Brenner SE. Association of gut microbiota with post-operative clinical course in Crohn’s disease. BMC Gastroenterol. 2013;13(1):131. doi:10.1186/1471-230X-13-131
66. Machiels K, Pozuelo del Río M, Martinez-De la Torre A, et al. Early Postoperative Endoscopic Recurrence in Crohn’s Disease Is Characterised by Distinct Microbiota Recolonisation. J Crohns Colitis. 2020;14(11): 1535-1546. doi:10.1093/ecco-jcc/jjaa081
67. Keshteli AH, Tso R, Dieleman LA, et al. A Distinctive Urinary Metabolomic Fingerprint Is Linked With Endoscopic Postoperative Disease Recurrence in Crohn’s Disease Patients. Inflamm Bowel Dis. 2018;24(4):861-870. doi:10.1093/ibd/izx070
68. Zhuang X, Tian Z, Li N, et al. Gut Microbiota Profiles and Microbial-Based Therapies in Post-operative Crohn’s Disease: A Systematic Review. Front Med (Lausanne). 2021;7. doi:10.3389/fmed.2020.615858
69. Rutgeerts P, Hiele M, Geboes K, et al. Controlled trial of metronidazole treatment for prevention of crohn’s recurrence after ileal resection. Gastroenterology. 1995;108(6): 1617-1621. doi:10.1016/0016-5085(95)90121-3
70. Rutgeerts P, van Assche G, Vermeire S, et al. Ornidazole for prophylaxis of postoperative Crohn’s disease recurrence: A randomized, double-blind, placebo-controlled trial. Gastroenterology. 2005;128 (4):856-861. doi:10.1053/j.gastro.2005.01.010
71. Herfarth HH, Katz JA, Hanauer SB, et al. Ciprofloxacin for the Prevention of Postoperative Recurrence in Patients with Crohnʼs Disease. Inflamm Bowel Dis. 2013; 19(5):1073-1079. doi:10.1097/01.MIB.0000428910.36091.10
72. Campieri M, Rizzello F, Venturi A, Poggioli G, Ugolini F. Combination of antibiotic and probiotic treatment is efficacious in prophylaxis of post-operative recurrence of Crohn’s disease: A randomized controlled study VS mesalamine. Gastroenterology. 2000;118(4): A781. doi:10.1016/S0016-5085(00)85267-1
73. Marteau P. Ineffectiveness of Lactobacillus johnsonii LA1 for prophylaxis of postoperative recurrence in Crohn’s disease: a randomised, double blind, placebo controlled GETAID trial. Gut. 2006;55(6):842-847. doi:10.1136/gut.2005.076604
74. van Gossum A, Dewit O, Louis E, et al. Multicenter randomized-controlled clinical trial of probiotics (Lactobacillus johnsonii, LA1) on early endoscopic recurrence of Crohnʼs disease after ileo-caecal resection. Inflamm Bowel Dis. 2007;13(2):135-142. doi:10.1002/ibd.20063
75. Fedorak RN, Feagan BG, Hotte N, et al. The Probiotic VSL#3 Has Anti-inflammatory Effects and Could Reduce Endoscopic Recurrence After Surgery for Crohn’s Disease. Clinical Gastroenterology and Hepatology. 2015;13(5):928-935.e2. doi:10.1016/j.cgh.2014.10.031
76. Chermesh I, Tamir A, Reshef R, et al. Failure of Synbiotic 2000 to Prevent Postoperative Recurrence of Crohn’s Disease. Dig Dis Sci. 2007;52(2):385-389. doi:10.1007/s10620-006-9549-7
77. Liu JZ, Anderson CA. Genetic studies of Crohn’s disease: Past, present and future. Best Pract Res Clin Gastroenterol. 2014;28(3): 373-386. doi:10.1016/j.bpg.2014.04.009
78. Jostins L, Ripke S, Weersma RK, et al. Host–microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature. 2012;491(7422):119-124. doi:10.1038/nature11582
79. Cleynen I, González JR, Figueroa C, et al. Genetic factors conferring an increased susceptibility to develop Crohn’s disease also influence disease phenotype: results from the IBDchip European Project. Gut. 2013;62(11): 1556-1565. doi:10.1136/gutjnl-2011-300777
80. Sidiq T, Yoshihama S, Downs I, Kobayashi KS. Nod2: A Critical Regulator of Ileal Microbiota and Crohn’s Disease. Front Immunol. 2016;7. doi:10.3389/fimmu.2016.00367
81. Büning C, Genschel J, Bühner S, et al. Mutations in the NOD2/CARD15 gene in Crohn’s disease are associated with ileocecal resection and are a risk factor for reoperation. Aliment Pharmacol Ther. 2004;19(10):1073-1078. doi:10.1111/j.1365-2036.2004.01967.x
82. Bhullar M. Prediction of Crohn’s disease aggression through NOD2 / CARD15 gene sequencing in an Australian cohort. World J Gastroenterol. 2014;20(17):5008. doi:10.3748/wjg.v20.i17.5008
83. Maconi G, Colombo E, Sampietro GM, et al. CARD15 Gene Variants and Risk of Reoperation in Crohn’s Disease Patients. Am J Gastroenterol. 2009;104(10):2483-2491. doi:10.1038/ajg.2009.413
84. Dang JT, Dang TT, Wine E, Dicken B, Madsen K, Laffin M. The Genetics of Postoperative Recurrence in Crohn Disease: A Systematic Review, Meta-analysis, and Framework for Future Work. Crohns Colitis 360. 2021;3(2). doi:10.1093/crocol/otaa094
85. Sehgal R, Berg A, Polinski JI, et al. Mutations in IRGM Are Associated With More Frequent Need for Surgery in Patients With Ileocolonic Crohn’s Disease. Dis Colon Rectum. 2012;55(2):115-121. doi:10.1097/DCR.0b013e31823ccea8
86. Germain A, Guéant RM, Chamaillard M, Bresler L, Guéant JL, Peyrin-Biroulet L. CARD8 gene variant is a risk factor for recurrent surgery in patients with Crohn’s disease. Digestive and Liver Disease. 2015;47(11):938-942. doi:10.1016/j.dld.2015.07.013
87. Gerich ME, Fleshner P, Panikkath D, et al. Mo1299 Genotype and Post-Operative Immunosuppression Impact Surgical Recurrence in Crohn’s Disease. Gastroenterology. 2013; 144(5):S-630. doi:10.1016/S0016-5085(13)62332-X
88. Laffin MR, Fedorak RN, Wine E, Dicken B, Madsen KL. A BACH2 Gene Variant Is Associated with Postoperative Recurrence of Crohn’s Disease. J Am Coll Surg. 2018;226(5): 902-908. doi:10.1016/j.jamcollsurg.2018.01.052