Laparoscopic versus open colorectal surgery for colon cancer: the effect of surgical trauma on the bacterial translocation. A prospective randomized study

Schietroma, Mario; Pessia, Beatrice; Carlei, Francesco; Cecilia, Emanuela Marina; Santis, Giuseppe De; Amicucci, Gianfranco

doi:10.1016/j.amjsurg.2014.09.031

Cited by 15 publications

(7 citation statements)

References 35 publications

(39 reference statements)

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“…Not only in the gastrointestinal tract but also outside of it in the skin dsRNA from damaged cells was shown to induce hair follicle regeneration via TLR3 (16). In contrast, a viral origin of dsRNA is supported by detection of microbial translocation upon intestinal surgery in mice (11,12) and in humans (49). With more than >10 12 particles, bacteriophages represent the majority of human gut viruses (50).…”

Section: Discussionmentioning

confidence: 99%

A Population of Radio-Resistant Macrophages in the Deep Myenteric Plexus Contributes to Postoperative Ileus Via Toll-Like Receptor 3 Signaling

et al. 2021

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Postoperative ileus (POI) is triggered by an innate immune response in the muscularis externa (ME) and is accompanied by bacterial translocation. Bacteria can trigger an innate immune response via toll-like receptor (TLR) activation, but the latter’s contribution to POI has been disproved for several TLRs, including TLR2 and TLR4. Herein we investigated the role of double-stranded RNA detection via TLR3 and TIR-domain-containing adapter-inducing interferon-β (TRIF) signaling pathway in POI. POI was induced by small bowel intestinal manipulation in wt, TRIF-/-, TLR3-/-, type I interferon receptor-/- and interferon-β reporter mice, all on C57BL/6 background, and POI severity was quantified by gene expression analysis, gastrointestinal transit and leukocyte extravasation into the ME. TRIF/TLR3 deficiency reduced postoperative ME inflammation and prevented POI. With bone marrow transplantation, RNA-sequencing, flow cytometry and immunohistochemistry we revealed a distinct TLR3-expressing radio-resistant MHCIIhiCX3CR1- IBA-1+ resident macrophage population within the deep myenteric plexus. TLR3 deficiency in these cells, but not in MHCIIhiCX3CR1+ macrophages, reduced cytokine expression in POI. While this might not be an exclusive macrophage-privileged pathway, the TLR3/TRIF axis contributes to proinflammatory cytokine production in MHCIIhiCX3CR1- IBA-1+ macrophages during POI. Deficiency in TLR3/TRIF protects mice from POI. These data suggest that TLR3 antagonism may prevent POI in humans.

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Section: Discussionmentioning

confidence: 99%

A Population of Radio-Resistant Macrophages in the Deep Myenteric Plexus Contributes to Postoperative Ileus Via Toll-Like Receptor 3 Signaling

et al. 2021

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“…51, 52 Importantly, a recent study demonstrated that bowel mobilization already led to bacterial translocation in patients. 40 Furthermore, patients with anastomotic leakage or who encountered bacterial translocation after a colectomy had poor disease-free survival, 41 indicating that bacterial contamination had a negative impact on long-term patient outcome. Even though this simplified surgical rat model does not completely reflect the human situation, as multiple peri- and post-operative factors (e.g.…”

Section: Discussionmentioning

confidence: 99%

“…39 Elevation of endotoxin levels in blood was accompanied by intestinal permeability, which suggested that the epithelial barrier was impaired after surgery. 39, 40 Since the liver is the first organ receiving blood from the intestines, bacterial components may activate KCs and PMNs and induce ROS production. Patients with positive bacterial translocation after surgery had significantly shorter disease-free survival, 41 supporting the negative impact of bacterial contamination after surgery on oncological outcome.…”

Section: Introductionmentioning

confidence: 99%

Spillage of bacterial products during colon surgery increases the risk of liver metastases development in a rat colon carcinoma model.

et al. 2018

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Surgical resection of the primary tumor provides the best chance of cure for patients with colorectal carcinoma (CRC). However, bacterial translocation during intestinal surgery has been correlated with poor long-term oncological outcome. Therefore, we investigated the influence of bacterial contamination during colon surgery on CRC liver metastases development. Blood and liver samples of patients undergoing resection of primary CRC or liver metastases were collected. Cell numbers, activation markers and inflammatory mediators were determined. Tumor cell adhesion and outgrowth after sham- or colectomy operations were determined in a rat model, in which tumor cells had been injected into the portal vein.White blood cells and granulocytes were increased in per- and post-operative patient blood samples. IL-6 was also increased post-operatively compared to the preoperative level. Expression of NOX-2, NOX-4 and polymorphonuclear cells (PMNs) numbers were elevated in post-operative human liver samples. In vitro stimulation of macrophages with plasma of rats after colectomy resulted in production of reactive oxygen species (ROS). Colectomy in rats increased D-lactate levels in plasma, supporting bacterial translocation. Decreased expression of tight junction molecules and increased tumor cell adhesion and outgrowth was observed. Treatment with a selective decontamination of the digestive tract (SDD) cocktail decreased tumor cell adherence after colectomy.In conclusion, postoperative bacterial translocation may activate liver macrophages and PMNs, resulting in ROS production. As we previously showed that ROS release led to liver vasculature damage, circulating tumor cells may adhere to exposed extracellular matrix and grow out into liver metastases. This knowledge is pivotal for development of therapeutic strategies to prevent surgery-induced liver metastases development.

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“…Colorectal surgery has been shown to lead to bacterial translocation into the circulation and abdominal cavity [60][61][62][63][64]. LPS has been detected in post-surgical plasma of patients [65,66] and elevation of LPS concentration in blood was accompanied by intestinal permeability, which suggest that the gut epithelial barrier is impaired post-operatively [67].…”

Section: Anastomotic Leakage and Bacterial Translocationmentioning

confidence: 99%

Surgery for Colorectal Cancer: A Trigger for Liver Metastases Development? New Insights into the Underlying Mechanisms

2021

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Surgery is a crucial intervention and provides the best chance of cure for patients with colorectal cancer. Experimental and clinical evidence, however, suggests that paradoxically surgery itself may precipitate or accelerate tumor recurrence and/or liver metastasis development. This review addresses the various aspects of surgery-induced metastasis formation and sheds light on the role of inflammation as potential trigger for metastasis development. Understanding these mechanisms may provide potential new perioperative interventions to improve treatment outcomes, and as such could transform the perioperative timeframe from a facilitator of metastatic progression to a window of opportunity to reduce the risk of liver metastasis development. Ultimately, this can potentially improve long-term survival rates and quality of life in patients with colorectal cancer.

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Laparoscopic versus open colorectal surgery for colon cancer: the effect of surgical trauma on the bacterial translocation. A prospective randomized study

Cited by 15 publications

References 35 publications

A Population of Radio-Resistant Macrophages in the Deep Myenteric Plexus Contributes to Postoperative Ileus Via Toll-Like Receptor 3 Signaling

A Population of Radio-Resistant Macrophages in the Deep Myenteric Plexus Contributes to Postoperative Ileus Via Toll-Like Receptor 3 Signaling

Spillage of bacterial products during colon surgery increases the risk of liver metastases development in a rat colon carcinoma model.

Surgery for Colorectal Cancer: A Trigger for Liver Metastases Development? New Insights into the Underlying Mechanisms

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