Postoperative infections are associated with adverse outcome after resection with curative intent for colorectal cancer

Tsujimoto, Hironori; Ueno, Hideki; Hashiguchi, Yojiro; Ono, Satoshi; Ichikura, Takashi; Hase, Kazuo

doi:10.3892/ol_00000022

Cited by 28 publications

(18 citation statements)

References 25 publications

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“…Although hypovolemia in the absence of surgical stress did lead to an increase in pulmonary metastases, our findings demonstrate that neither severe intraoperative hypovolemia nor hypothermia impact the prometastatic effects of surgical stress. Correlative clinical studies confirm that postoperative infections following surgery can accelerate the time to cancer recurrence [ 45 – 47 ]. Here, using murine models we demonstrate that polymicrobial sepsis in conjunction with surgical stress facilitates the development of perioperative lung metastases.…”

Section: Discussionmentioning

confidence: 99%

Sepsis increases perioperative metastases in a murine model

et al. 2018

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BackgroundCancer surgery can promote tumour metastases and worsen prognosis, however, the effect of perioperative complications on metastatic disease remains unclear. In this study we sought to evaluate the effect of common perioperative complications including perioperative blood loss, hypothermia, and sepsis on tumour metastases in a murine model.MethodsPrior to surgery, pulmonary metastases were established by intravenous challenge of CT26LacZ colon cancer cells in BALB/c mice. Surgical stress was generated through partial hepatectomy (PH) or left nephrectomy (LN). Sepsis was induced by puncturing the cecum to express stool into the abdomen. Hemorrhagic shock was induced by removal of 30% of total blood volume (i.e. stage 3 hemorrhage) via the saphenous vein. Hypothermia was induced by removing the heating apparatus during surgery and lowering core body temperatures to 30 °C. Lung tumour burden was quantified 3 days following surgery.ResultsSurgically stressed mice subjected to stage 3 hemorrhage or hypothermia did not show an additional increase in lung tumour burden. In contrast, surgically stressed mice subjected to intraoperative sepsis demonstrated an additional 2-fold increase in the number of tumour metastases. Furthermore, natural killer (NK) cell function, as assessed by YAC-1 tumour cell lysis, was significantly attenuated in surgically stressed mice subjected to intraoperative sepsis. Both NK cell-mediated cytotoxic function and lung tumour burden were improved with perioperative administration of polyI:C, which is a toll-like receptor (TLR)-3 ligand.ConclusionsPerioperative sepsis alone, but not hemorrhage or hypothermia, enhances the prometastatic effect of surgery in murine models of cancer. Understanding the cellular mechanisms underlying perioperative immune suppression will facilitate the development of immunomodulation strategies that can attenuate metastatic disease.

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Section: Discussionmentioning

confidence: 99%

Sepsis increases perioperative metastases in a murine model

et al. 2018

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“…Following screening of titles and abstracts, 25 papers were retrieved in full‐text form and assessed for eligibility. All 25 articles reported the effects of postoperative complications on long‐term survival; however, eight of these were of poor methodological quality as judged by a NOS score of 6 or less and were therefore excluded ( Tables S1 and S2 , supporting information). Poor NOS scores were due to inadequate or unreported follow‐up, lack of patient demographic information, and lack of appropriate controls for confounding factors (such as use of unadjusted univariable regression models).…”

Section: Resultsmentioning

confidence: 99%

“…The impact of excluded poor‐quality studies was assessed by a further sensitivity analysis. Of eight excluded studies, three reported HRs suitable for analysis ( Table S3 , supporting information). Inclusion of these in meta‐analysis had no effect on findings for overall survival, with similar results for all complications (HR 1·29, 1·22 to 1·36; P < 0·001) and infectious complications (1·52, 1·42 to 1·62; P < 0·001).…”

Section: Resultsmentioning

confidence: 99%

Meta-analysis of the effect of postoperative in-hospital morbidity on long-term patient survival

Pucher

Aggarwal

Qurashi

et al. 2014

British Journal of Surgery

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Background: Major surgery is associated with high rates of postoperative complications, many of which are deemed preventable. It has been suggested that these complications not only present a risk to patients in the short term, but may also reduce long-term survival. The aim of this review was to examine the effects of postoperative complications on long-term survival. Methods: MEDLINE, Web of Science and reference lists of relevant articles were searched up to July 2013. Studies assessing only procedure-specific, or technical failure-related, complications were excluded, as were studies of poor methodological quality. Meta-analysis was performed using a random-effects model. Risk of bias was assessed using funnel plots. Results: Eighteen eligible studies were included, comprising results for 134 785 patients with an overall complication rate of 22⋅6 (range 10⋅6-69) per cent. The studies included operations for both benign and malignant disease. Median follow-up was 43 (range 28-96) months. Meta-analysis demonstrated reduced overall survival after any postoperative complication for ten studies with eligible data (20 755 patients), with a hazard ratio (HR) of 1⋅28 (95 per cent confidence interval 1⋅21 to 1⋅34). Similar results were found for overall survival following infectious complications: HR 1⋅92 (1⋅50 to 2⋅35). In analyses of disease-free survival the HR was 1⋅26 (1⋅10 to 1⋅42) for all postoperative complications and 1⋅55 (1⋅12 to 1⋅99) for infectious complications. Inclusion of poor-quality studies in a sensitivity analysis had no effect on the results.Conclusion: Postoperative complications have a negative effect on long-term survival. This relationship appears to be stronger for infectious complications.

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“…Although hypovolemia in the absence of surgical stress did lead to an increase in lung metastases our findings demonstrate that neither severe intraoperative hypovolemia nor hypothermia impact the prometastatic effects of surgical stress. Correlative clinical studies confirm that postoperative infections following surgery can accelerate the time to cancer recurrence [46][47][48] . Here, using murine models we demonstrate that polymicrobial sepsis in conjunction with surgical stress facilitates the development of perioperative lung metastases.…”

Section: Discussionmentioning

confidence: 99%