{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T23:06:45Z","timestamp":1778540805853,"version":"3.51.4"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2021,8,28]],"date-time":"2021-08-28T00:00:00Z","timestamp":1630108800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,8,28]],"date-time":"2021-08-28T00:00:00Z","timestamp":1630108800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["NE 1834\/2-1"],"award-info":[{"award-number":["NE 1834\/2-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/n\/a","name":"Clinician scientist scholarship, Medical School, Technical University of Munich","doi-asserted-by":"publisher","award":["NE 1834\/2-1"],"award-info":[{"award-number":["NE 1834\/2-1"]}],"id":[{"id":"10.13039\/n\/a","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/n\/a","name":"Else Kr\u00f6ner Fresenius\/ Technical University Munich","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/n\/a","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005713","name":"Technische Universit\u00e4t M\u00fcnchen","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005713","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Int J Colorectal Dis"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Anastomotic leakage represents a major complication following resections in colorectal surgery. Among others, intestinal inflammation such as in inflammatory bowel disease is a significant risk factor for disturbed anastomotic healing. Despite technical advancements and several decades of focused research, the underlying mechanisms remain incompletely understood. Animal experiments will remain the backbone of this research in the near future. Here, instructions on a standardized and reproducible murine model of preoperative colitis and colorectal anastomosis formation are provided to amplify research on anastomotic healing during inflammatory disease.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We demonstrate the combination of experimental colitis and colorectal anastomosis formation in a mouse model. The model allows for monitoring of anastomotic healing during inflammatory disease through functional outcomes, clinical scores, and endoscopy and histopathological examination, as well as molecular analysis.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Discussion<\/jats:title>\n                <jats:p>Postoperative weight loss is used as a parameter to monitor general recovery. Functional stability can be measured by recording bursting pressure and location. Anastomotic healing can be evaluated macroscopically from the luminal side by endoscopic scoring and from the extraluminal side by assessing adhesion and abscess formation or presence of dehiscence. Histologic examination allows for detailed evaluation of the healing process.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>The murine model presented in this paper combines adjustable levels of experimental colitis with a standardized method for colorectal anastomosis formation. Extensive options for sample analysis and evaluation of clinical outcomes allow for detailed research of the mechanisms behind defective anastomotic healing.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00384-021-04014-5","type":"journal-article","created":{"date-parts":[[2021,8,28]],"date-time":"2021-08-28T17:02:48Z","timestamp":1630170168000},"page":"2247-2259","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Intestinal anastomotic healing models during experimental colitis"],"prefix":"10.1007","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7399-4144","authenticated-orcid":false,"given":"J. R. E.","family":"Miltschitzky","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Z.","family":"Clees","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3188-2160","authenticated-orcid":false,"given":"M.-C.","family":"Weber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2114-8736","authenticated-orcid":false,"given":"V.","family":"Vieregge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. L.","family":"Walter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"Friess","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7341-4296","authenticated-orcid":false,"given":"S.","family":"Reischl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8361-3934","authenticated-orcid":false,"given":"P.-A.","family":"Neumann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,8,28]]},"reference":[{"issue":"5","key":"4014_CR1","doi-asserted-by":"publisher","first-page":"930","DOI":"10.1097\/SLA.0b013e3182a6f2fc","volume":"259","author":"PM Krarup","year":"2014","unstructured":"Krarup PM, Nordholm-Carstensen A, Jorgensen LN, Harling H (2014) Anastomotic leak increases distant recurrence and long-term mortality after curative resection for colonic cancer: a nationwide cohort study. Ann Surg 259(5):930\u2013938. https:\/\/doi.org\/10.1097\/SLA.0b013e3182a6f2fc","journal-title":"Ann Surg"},{"issue":"10","key":"4014_CR2","doi-asserted-by":"publisher","first-page":"e661","DOI":"10.1111\/j.1463-1318.2012.03079.x","volume":"14","author":"PM Krarup","year":"2012","unstructured":"Krarup PM, Jorgensen LN, Andreasen AH, Harling H, Danish Colorectal Cancer G (2012) A nationwide study on anastomotic leakage after colonic cancer surgery. Colorectal Dis 14(10):e661-667. https:\/\/doi.org\/10.1111\/j.1463-1318.2012.03079.x","journal-title":"Colorectal Dis"},{"issue":"9","key":"4014_CR3","doi-asserted-by":"publisher","first-page":"662","DOI":"10.1111\/codi.12618","volume":"16","author":"HC Pommergaard","year":"2014","unstructured":"Pommergaard HC, Gessler B, Burcharth J, Angenete E, Haglind E, Rosenberg J (2014) Preoperative risk factors for anastomotic leakage after resection for colorectal cancer: a systematic review and meta-analysis. Colorectal Dis 16(9):662\u2013671. https:\/\/doi.org\/10.1111\/codi.12618","journal-title":"Colorectal Dis"},{"issue":"5","key":"4014_CR4","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1002\/bjs.9697","volume":"102","author":"FD McDermott","year":"2015","unstructured":"McDermott FD, Heeney A, Kelly ME, Steele RJ, Carlson GL, Winter DC (2015) Systematic review of preoperative, intraoperative and postoperative risk factors for colorectal anastomotic leaks. Br J Surg 102(5):462\u2013479. https:\/\/doi.org\/10.1002\/bjs.9697","journal-title":"Br J Surg"},{"issue":"5","key":"4014_CR5","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1002\/bjs.4085","volume":"90","author":"JA Smith","year":"2003","unstructured":"Smith JA, King PM, Lane RH, Thompson MR (2003) Evidence of the effect of \u201cspecialization\u201d on the management, surgical outcome and survival from colorectal cancer in Wessex. Br J Surg 90(5):583\u2013592. https:\/\/doi.org\/10.1002\/bjs.4085","journal-title":"Br J Surg"},{"issue":"2","key":"4014_CR6","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1097\/SLA.0b013e3180603024","volume":"246","author":"P Matthiessen","year":"2007","unstructured":"Matthiessen P, Hallbook O, Rutegard J, Simert G, Sjodahl R (2007) Defunctioning stoma reduces symptomatic anastomotic leakage after low anterior resection of the rectum for cancer: a randomized multicenter trial. Ann Surg 246(2):207\u2013214. https:\/\/doi.org\/10.1097\/SLA.0b013e3180603024","journal-title":"Ann Surg"},{"issue":"7","key":"4014_CR7","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1002\/bjs.9776","volume":"102","author":"ST Yauw","year":"2015","unstructured":"Yauw ST, Wever KE, Hoesseini A, Ritskes-Hoitinga M, van Goor H (2015) Systematic review of experimental studies on intestinal anastomosis. Br J Surg 102(7):726\u2013734. https:\/\/doi.org\/10.1002\/bjs.9776","journal-title":"Br J Surg"},{"issue":"3","key":"4014_CR8","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1016\/S0039-6109(05)70568-5","volume":"77","author":"FJ Thornton","year":"1997","unstructured":"Thornton FJ, Barbul A (1997) Healing in the gastrointestinal tract. Surg Clin North Am 77(3):549\u2013573","journal-title":"Surg Clin North Am"},{"issue":"3","key":"4014_CR9","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1002\/micr.20197","volume":"26","author":"SK Thompson","year":"2006","unstructured":"Thompson SK, Chang EY, Jobe BA (2006) Clinical review: healing in gastrointestinal anastomoses, part I. Microsurgery 26(3):131\u2013136. https:\/\/doi.org\/10.1002\/micr.20197","journal-title":"Microsurgery"},{"issue":"2","key":"4014_CR10","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1002\/bjs.1800570208","volume":"57","author":"JC Goligher","year":"1970","unstructured":"Goligher JC, Graham NG, De Dombal FT (1970) Anastomotic dehiscence after anterior resection of rectum and sigmoid. Br J Surg 57(2):109\u2013118","journal-title":"Br J Surg"},{"issue":"4","key":"4014_CR11","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1016\/0002-9610(78)90030-2","volume":"135","author":"J Sharefkin","year":"1978","unstructured":"Sharefkin J, Joffe N, Silen W, Fromm D (1978) Anastomotic dehiscence after low anterior resection of the rectum. Am J Surg 135(4):519\u2013523","journal-title":"Am J Surg"},{"issue":"4","key":"4014_CR12","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1097\/00024382-199510000-00001","volume":"4","author":"LA DiPietro","year":"1995","unstructured":"DiPietro LA (1995) Wound healing: the role of the macrophage and other immune cells. Shock 4(4):233\u2013240","journal-title":"Shock"},{"issue":"1","key":"4014_CR13","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1016\/j.jss.2013.10.013","volume":"187","author":"E Rijcken","year":"2014","unstructured":"Rijcken E, Sachs L, Fuchs T, Spiegel HU, Neumann PA (2014) Growth factors and gastrointestinal anastomotic healing. J Surg Res 187(1):202\u2013210. https:\/\/doi.org\/10.1016\/j.jss.2013.10.013","journal-title":"J Surg Res"},{"issue":"3","key":"4014_CR14","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1016\/S0039-6109(02)00196-2","volume":"83","author":"DA Dubay","year":"2003","unstructured":"Dubay DA, Franz MG (2003) Acute wound healing: the biology of acute wound failure. Surg Clin North Am 83(3):463\u2013481. https:\/\/doi.org\/10.1016\/S0039-6109(02)00196-2","journal-title":"Surg Clin North Am"},{"issue":"5","key":"4014_CR15","doi-asserted-by":"publisher","first-page":"389","DOI":"10.4240\/wjgs.v8.i5.389","volume":"8","author":"M Nerstrom","year":"2016","unstructured":"Nerstrom M, Krarup PM, Jorgensen LN, Agren MS (2016) Therapeutic improvement of colonic anastomotic healing under complicated conditions: a systematic review. World J Gastrointest Surg 8(5):389\u2013401. https:\/\/doi.org\/10.4240\/wjgs.v8.i5.389","journal-title":"World J Gastrointest Surg"},{"issue":"7","key":"4014_CR16","doi-asserted-by":"publisher","first-page":"1295","DOI":"10.1038\/nprot.2017.044","volume":"12","author":"S Wirtz","year":"2017","unstructured":"Wirtz S, Popp V, Kindermann M, Gerlach K, Weigmann B, Fichtner-Feigl S, Neurath MF (2017) Chemically induced mouse models of acute and chronic intestinal inflammation. Nat Protoc 12(7):1295\u20131309. https:\/\/doi.org\/10.1038\/nprot.2017.044","journal-title":"Nat Protoc"},{"issue":"3","key":"4014_CR17","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0194249","volume":"13","author":"PA Neumann","year":"2018","unstructured":"Neumann PA, Twardy V, Becker F, Geyer C, Schwegmann K, Mohr A, Faust A, Lenz P, Rijcken E (2018) Assessment of MMP-2\/-9 expression by fluorescence endoscopy for evaluation of anastomotic healing in a murine model of anastomotic leakage. PLoS One 13(3):e0194249. https:\/\/doi.org\/10.1371\/journal.pone.0194249","journal-title":"PLoS One"},{"issue":"3","key":"4014_CR18","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1159\/000330748","volume":"47","author":"HC Pommergaard","year":"2011","unstructured":"Pommergaard HC, Rosenberg J, Schumacher-Petersen C, Achiam MP (2011) Choosing the best animal species to mimic clinical colon anastomotic leakage in humans: a qualitative systematic review. Eur Surg Res 47(3):173\u2013181. https:\/\/doi.org\/10.1159\/000330748","journal-title":"Eur Surg Res"},{"issue":"10","key":"4014_CR19","doi-asserted-by":"publisher","first-page":"1699","DOI":"10.1007\/s10350-004-0647-3","volume":"47","author":"J Migaly","year":"2004","unstructured":"Migaly J, Lieberman J, Long W, Fisher C, Rolandelli RH (2004) Effect of adenoviral-mediated transfer of transforming growth factor-beta1 on colonic anastomotic healing. Dis Colon Rectum 47(10):1699\u20131705","journal-title":"Dis Colon Rectum"},{"issue":"1","key":"4014_CR20","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/0002-9610(92)90255-P","volume":"163","author":"JD Phillips","year":"1992","unstructured":"Phillips JD, Kim CS, Fonkalsrud EW, Zeng H, Dindar H (1992) Effects of chronic corticosteroids and vitamin A on the healing of intestinal anastomoses. Am J Surg 163(1):71\u201377","journal-title":"Am J Surg"},{"issue":"2","key":"4014_CR21","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1016\/j.jpedsurg.2007.10.016","volume":"43","author":"M Fedakar-Senyucel","year":"2008","unstructured":"Fedakar-Senyucel M, Bingol-Kologlu M, Vargun R, Akbay C, Sarac FN, Renda N, Hasirci N, Gollu G, Dindar H (2008) The effects of local and sustained release of fibroblast growth factor on wound healing in esophageal anastomoses. J Pediatr Surg 43(2):290\u2013295. https:\/\/doi.org\/10.1016\/j.jpedsurg.2007.10.016","journal-title":"J Pediatr Surg"},{"key":"4014_CR22","doi-asserted-by":"publisher","DOI":"10.1093\/ibd\/izab008","author":"S Reischl","year":"2021","unstructured":"Reischl S, Lee JH, Miltschitzky JRE, Vieregge V, Walter RL, Twardy V, Kasajima A, Friess H, Kamaly N, Neumann PA (2021) Ac2-26-Nanoparticles induce resolution of intestinal inflammation and anastomotic healing via inhibition of NF-kappaB signaling in a model of perioperative colitis. Inflamm Bowel Dis. https:\/\/doi.org\/10.1093\/ibd\/izab008","journal-title":"Inflamm Bowel Dis"}],"container-title":["International Journal of Colorectal Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00384-021-04014-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00384-021-04014-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00384-021-04014-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,8]],"date-time":"2021-09-08T14:16:52Z","timestamp":1631110612000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00384-021-04014-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,28]]},"references-count":22,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2021,10]]}},"alternative-id":["4014"],"URL":"https:\/\/doi.org\/10.1007\/s00384-021-04014-5","relation":{},"ISSN":["0179-1958","1432-1262"],"issn-type":[{"value":"0179-1958","type":"print"},{"value":"1432-1262","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,28]]},"assertion":[{"value":"10 August 2021","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 August 2021","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}