Despite antibiotics and sterile technique, postoperative infections remain a real and present danger to patients. Recent estimates suggest that 50% of the pathogens associated with postoperative infections have become resistant to the standard antibiotics used for prophylaxis. Risk factors identified in such cases include obesity and antibiotic exposure. To study the combined effect of obesity and antibiotic exposure on postoperative infection, mice were allowed to gain weight on an obesogenic Western-type diet (WD), administered antibiotics and then subjected to an otherwise recoverable sterile surgical injury (30% hepatectomy). The feeding of a WD alone resulted in a major imbalance of the cecal microbiota characterized by a decrease in diversity, loss of Bacteroidetes, a bloom in Proteobacteria, and the emergence of antibiotic-resistant organisms among the cecal microbiota. When WD-fed mice were administered antibiotics and subjected to 30% liver resection, lethal sepsis, characterized by multiple-organ damage, developed. Notable was the emergence and systemic dissemination of multidrug-resistant (MDR) pathobionts, including carbapenem-resistant, extended-spectrum β-lactamase-producing Serratia marcescens, which expressed a virulent and immunosuppressive phenotype. Analysis of the distribution of exact sequence variants belonging to the genus Serratia suggested that these strains originated from the cecal mucosa. No mortality or MDR pathogens were observed in identically treated mice fed a standard chow diet. Taken together, these results suggest that consumption of a Western diet and exposure to certain antibiotics may predispose to life-threating postoperative infection associated with MDR organisms present among the gut microbiota. IMPORTANCE Obesity remains a prevalent and independent risk factor for life-threatening infection following major surgery. Here, we demonstrate that when mice are fed an obesogenic Western diet (WD), they become susceptible to lethal sepsis with multiple organ damage after exposure to antibiotics and an otherwise-recoverable surgical injury. Analysis of the gut microbiota in this model demonstrates that WD alone leads to loss of Bacteroidetes, a bloom of Proteobacteria, and evidence of antibiotic resistance development even before antibiotics are administered. After antibiotics and surgery, lethal sepsis with organ damage developed in in mice fed a WD with the appearance of multidrug-resistant pathogens in the liver, spleen, and blood. The importance of these findings lies in exposing how the selective pressures of diet, antibiotic exposure, and surgical injury can converge on the microbiome, resulting in lethal sepsis and organ damage without the introduction of an exogenous pathogen.
Background: Both obesity and the presence of collagenolytic bacterial strains (Enterococcus faecalis) can increase the risk of anastomotic leak. The aim of this study was to determine whether mice chronically fed a high-fat Western-type diet (WD) develop anastomotic leak in association with altered microbiota, and whether this can be mitigated by a short course of standard chow diet (SD; low fat/high fibre) before surgery.Methods: Male C57BL/6 mice were assigned to either SD or an obesogenic WD for 6 weeks followed by preoperative antibiotics and colonic anastomosis. Microbiota were analysed longitudinally after operation and correlated with healing using an established anastomotic healing score. In reiterative experiments, mice fed a WD for 6 weeks were exposed to a SD for 2, 4 and 6 days before colonic surgery, and anastomotic healing and colonic microbiota analysed.Results: Compared with SD-fed mice, WD-fed mice demonstrated an increased risk of anastomotic leak, with a bloom in the abundance of Enterococcus in lumen and expelled stool (65-90 per cent for WD versus 4-15 per cent for SD; P = 0⋅010 for lumen, P = 0⋅013 for stool). Microbiota of SD-fed mice, but not those fed WD, were restored to their preoperative composition after surgery. Anastomotic healing was significantly improved when WD-fed mice were exposed to a SD diet for 2 days before antibiotics and surgery (P < 0⋅001).
These data indicate that oral intake of ABA-PEG20k-Pi20 may be an effective agent to contain the virulence of E. faecalis and may prevent anastomotic leak caused by this organism. Clinical relevance Progress in understanding the pathogenesis of anastomotic leak continues to point to intestinal bacteria as key causative agents. The presence of pathogens such as Enterococcus faecalis that predominate on anastomotic tissues despite antibiotic use, coupled with their ability to produce collagenase, appears to alter the process of healing that leads to leakage. Further antibiotic administration may seem logical, but carries the unwanted risk of eliminating the normal microbiome, which functions competitively to exclude and suppress the virulence of pathogens such as E. faecalis. Therefore, non-antibiotic strategies that can suppress the production of collagenase by E. faecalis without affecting its growth, or potentially normal beneficial microbiota, may have unique advantages. The findings of this study demonstrate that drinking a phosphate-based polymer can achieve the goal of preventing anastomotic leak by suppressing collagenase production in E. faecalis without affecting its growth.
Background Image‐guided surgery could help obtain clear (≥5.0 mm) resection margins. This feasibility study investigated ultrasound‐guided resection accuracy of buccal mucosa squamous cell carcinoma (BMSCC). Methods MRI and ultrasound measurements of tumor thickness were compared to histology in 13 BMSCC‐patients. Ultrasound measured margins (at five locations) on the specimen were compared to the corresponding histological margins. Results Accuracy of in‐ and ex‐vivo ultrasound (mean deviation from histology: 1.6 mm) for measuring tumor thickness was comparable to MRI (mean deviation from histology: 2.6 mm). The sensitivity to detect clear margins using ex‐vivo ultrasound was low (48%). If an ex‐vivo ultrasound cutoff of ≥7.5 mm would be used, the sensitivity would increase to 86%. Conclusions Ultrasound‐guided resection of BMSCC's is feasible. In‐ and ex‐vivo ultrasound measure tumor thickness in BMSCC accurately. We recommend ≥7.5 mm resection margins on ex‐vivo ultrasound to obtain histological clear margins. Additional research is required to establish the effect of 7.5 mm ultrasound cutoff.
Background: The adequate surgical margin for local control of buccal mucosa squamous cell carcinoma (BMSCC) is under debate. This study investigates surgical margins and other factors associated with local recurrence free survival (LRFS) in a large cohort of BMSCC patients.Methods: Multiple factors were evaluated retrospectively in 97 patients with BMSCC. Cox-regression and Kaplan-Meier curves were used for analysis.Results: The local recurrence rate was 23%. The tumor-free margin was <5.0 mm in 89% of the patients and the deep margin was significantly more often inadequate. Multivariate analysis associated pT3-classification, former smokers, tumor-free margin status, and postoperative (chemo)radiation (PO (ch)RT) with local recurrence. Re-resections did not improve LRFS in patients with <5.0 mm tumor-free margins.Conclusions: Adequate tumor-free margins are pivotal for LRFS of BMSCC. PO(ch)RT, not re-resection, can improve LRFS in patients with <5.0 mm tumor-free margins.
Background Cholesteatoma is a benign but destructive epithelial lesion in the middle ear and/or mastoid. It is hard to translate data from previous research to daily clinical practice. In this study, factors influencing recurrence rates in daily clinical practice were identified. Method The study included 67 patients who were treated for a cholesteatoma with combined approach tympanoplasty. The average follow-up time was 35 months. Results The recurrence rate was 23.3 per cent in adults and 45.5 per cent in children. Predictors of recurrence were younger age and a low tegmen. A cholesteatoma in a child and the simultaneous presence of a low tegmen led to recurrence in 82.8 per cent of the patients. Conclusion Patients – especially children – with a low tegmen have an increased risk of recurrence. It is recommended that ENT surgeons be aware of recurrence in children, particularly in the case of a low tegmen.
Purpose Anastomotic leak (AL) is a serious complication following colorectal surgery. Atherosclerosis causes inadequate anastomotic perfusion and is suggested to be a risk factor for AL. The aim of this study was to investigate the association of mesenteric occlusive disease on preoperative computed tomography (CT) scan with AL after left-sided colon or rectal cancer surgery. Methods This was a retrospective, multicenter cohort study including 1273 patients that underwent left-sided or rectal cancer resection between 2009 and 2018 from three hospitals in the Netherlands. AL patients were 1:1 matched with non-leak patients and preoperative contrast-enhanced CT-scans were retrospectively analyzed for mesenteric atherosclerotic lesions. The main outcome measure was the presence of mesenteric occlusive disease on the preoperative CT-scan. Results Anastomotic leak developed in 6% of 1273 patients (N = 76). Low anterior resection and stage I–III disease were statistically significant associated with AL (p = 0.01, p = 0.04). No other statistically significant differences in patient characteristics between AL and non-leak patients were found. A clinically significant stenosis (≥ 70–100%) of the inferior mesenteric artery was statistically significant more frequent present in AL patients, compared to non-leak patients (p < 0.01). No statistically significant differences in the presence of mesenteric occlusive disease of the celiac artery and superior mesenteric artery between AL patients and non-leak patients were found. Conclusion Mesenteric occlusive disease of the IMA on preoperative CT-scan is associated with AL after left-sided colon or rectal resection for cancer. Preoperative identification of high-risk patients with a preoperative CT-scan of the mesenteric vasculature might be useful to reduce the risk of AL.
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