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Exploratory cohort study reveals elevated anastomotic collagenase activity in esophageal cancer patients with leaks, suggesting a potential bacterial mechanism.
Topic Esophageal Cancer: Surgical Treatment of Esophageal Cancer – early outcomes and complications Background The etiopathogenesis of anastomotic leakage (AL) after esophagectomy is inadequately understood. In colorectal surgery, AL has been linked with phenotypic switching of commensal bacteria to pathogenic collagenase-producing bacteria. We aimed to explore for the first time if collagenase activity might also play a role in AL after esophagectomy for cancer. Methods Samples were endoscopically collected with cytology brushes at diagnosis of AL (n=4) or delayed conduit emptying (control group,n=3). In AL-patients, anastomoses was first sampled on the side opposite to the AL and second on the AL itself. In control patients two opposite sides were sampled. Collagenase activity was evaluated on a multimode microplate reader using fluorescein-labeled dye quenched collagen by comparing activity at 90-minutes to collagenase from Clostridium histolyticum, and by using Relative Fluorescence Units (RFU) at 12-hours. Samples were grouped according to sampling sequence. Collagenase activity was compared between AL and control patients using the Mann-Whitney U test. Results Patients with AL were sampled on postoperative day 11-24, on average 2.5±2.1 days after diagnosis, and patients in the control group on days 5-7. AL-severity was grade 2-3 and Clavien-Dindo IIIb-IVb. A non-significant trend for higher average collagenase activity (both sampling sites) was found in the AL group versus in the control group (4.60±3.8 and 0.73±0.5 respectively). Differences in average RFU were however significant in this exploratory cohort (37551±13403 in the AL-group,13835±8573 in the control group; p= 0.034). Of note, in patients with AL, the collagenase activity was similar between samples taken at the AL and on the opposite side. Conclusion Patients with AL after esophagectomy for cancer had higher collagenase activity on the anastomosis than patients without AL, mirroring earlier research in colorectal surgery suggesting a bacterial etiopathogenesis.
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Seurs et al. (2026) studied this question.
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