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Proceedings of the first international summit on intestinal anastomotic leak, Chicago, Illinois, October 4-5, 2012.

ABSTRACT: The first international summit on anastomotic leak was held in Chicago in October, 2012 to assess current knowledge in the field and develop novel lines of inquiry. The following report is a summary of the proceedings with commentaries and future prospects for clinical trials and laboratory investigations.Anastomotic leakage remains a devastating problem for the patient, and a continuing challenge to the surgeon operating on high-risk areas of the gastrointestinal tract such as the esophagus and rectum. Despite the traditional wisdom that anastomotic leak is because of technique, evidence to support this is weak-to-non-existent. Outcome data continue to demonstrate that expert high-volume surgeons working in high-volume centers continue to experience anastomotic leaks and that surgeons cannot predict reliably which patients will leak.A one and one-half day summit was held and a small working group assembled to review current practices, opinions, scientific evidence, and potential paths forward to understand and decrease the incidence of anastomotic leak.RESULTS of a survey of the opinions of the group demonstrated that the majority of participants believe that anastomotic leak is a complicated biologic problem whose pathogenesis remains ill-defined. The group opined that anastomotic leak is underreported clinically, it is not because of technique except when there is gross inattention to it, and that results from animal models are mostly irrelevant to the human condition.A fresh and unbiased examination of the causes and strategies for prevention of anastomotic leak needs to be addressed by a continuous working group of surgeons, basic scientists, and clinical trialists to realize a real and significant reduction in its incidence and morbidity. Such a path forward is discussed.

SUBMITTER: Shogan BD

PROVIDER: S-EPMC4382716 | biostudies-other | 2014 Oct

REPOSITORIES: biostudies-other

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Project description:The most feared complication following intestinal resection is anastomotic leakage. In high risk areas (esophagus/rectum) where neoadjuvant chemoradiation is used, the incidence of anastomotic leaks remains unacceptably high (? 10%) even when performed by specialist surgeons in high volume centers. The aims of this study were to test the hypothesis that anastomotic leakage develops when pathogens colonizing anastomotic sites become in vivo transformed to express a tissue destroying phenotype. We developed a novel model of anastomotic leak in which rats were exposed to pre-operative radiation as in cancer surgery, underwent distal colon resection and then were intestinally inoculated with Pseudomonas aeruginosa, a common colonizer of the radiated intestine. Results demonstrated that intestinal tissues exposed to preoperative radiation developed a significant incidence of anastomotic leak (>60%; p<0.01) when colonized by P. aeruginosa compared to radiated tissues alone (0%). Phenotype analysis comparing the original inoculating strain (MPAO1- termed P1) and the strain retrieved from leaking anastomotic tissues (termed P2) demonstrated that P2 was altered in pyocyanin production and displayed enhanced collagenase activity, high swarming motility, and a destructive phenotype against cultured intestinal epithelial cells (i.e. apoptosis, barrier function, cytolysis). Comparative genotype analysis between P1 and P2 revealed a single nucleotide polymorphism (SNP) mutation in the mexT gene that led to a stop codon resulting in a non-functional truncated protein. Replacement of the mutated mexT gene in P2 with mexT from the original parental strain P1 led to reversion of P2 to the P1 phenotype. No spontaneous transformation was detected during 20 passages in TSB media. Use of a novel virulence suppressing compound PEG/Pi prevented P. aeruginosa transformation to the tissue destructive phenotype and prevented anastomotic leak in rats. This work demonstrates that in vivo transformation of microbial pathogens to a tissue destroying phenotype may have important implications in the pathogenesis of anastomotic leak.

Project description:Background:The In the Trenches series of cutting-edge knowledge sharing events on impact for front-line experts and practitioners provides an engagement platform for diverse stakeholders across government, research funding organizations, industry, and academia to share emerging knowledge and practical experiences. The second event of the series In the Trenches: Implementation to Impact International Summit was held in Banff, Alberta, Canada, on June 7-8, 2019. The overarching vision for the Summit was to create an engagement platform for addressing key challenges and finding practical solutions to move from implementation (i.e. putting findings into effect) to impact (i.e. creating benefits to society and the economy). Processes and proceedings:The Summit used diverse approaches to facilitate active engagement and knowledge sharing between 80 delegates across sectors and jurisdictions. Summit sessions mostly consisted of short talks and moderated panels grouped into eight thematic sessions. Each presentation included a summary of Key Messages, along with a summary of the Actionable Insights which concluded each session. The presentations and discussions are analysed, synthesized and described in this proceedings paper using a systems approach. This demonstrates how the Summit focused on each of the necessary functions (and associated components) that should be undertaken, and combined, for effective research and innovation: stewardship and governance, securing finance, creating capacity, and producing and using research. The approach also identifies relevant challenges. Conclusions:There is increased interest globally in the benefits that can accrue from adopting a systems approach to research and innovation. Various organizations in Canada and internationally have made considerable progress on Implementation to Impact, often as a result of well-planned initiatives. The Summit highlights the value of 1) collaboration between researchers and potential users, and 2) the adoption by funders of approaches involving an increasing range of responsibilities and activities. The Summit website (https://inthetrenchessummit.com/) will be periodically updated with new resources and information about future In the Trenches events.

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Proceedings of the first international summit on intestinal anastomotic leak, Chicago, Illinois, October 4-5, 2012.

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