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

Simran Grewal, Rianne Korthouwer, Marijn Bögels, Rens Braster, Niels Heemskerk, Andries E Budding, Stephan M Pouw, Jack van Horssen, Marjolein Ankersmit, Jeroen Meijerink, Petrousjka van den Tol, Steven Oosterling, Jaap Bonjer, Nuray Gül, Marjolein van Egmond

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)e1461302
JournalOncoImmunology
Volume7
Issue number9
DOIs
Publication statusPublished - 2018

Cite this

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title = "Spillage of bacterial products during colon surgery increases the risk of liver metastases development in a rat colon carcinoma model",
abstract = "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.",
keywords = "colorectal tumor surgery, bacterial translocation, macrophages, liver metastases, reactive oxygen species",
author = "Simran Grewal and Rianne Korthouwer and Marijn B{\"o}gels and Rens Braster and Niels Heemskerk and Budding, {Andries E} and Pouw, {Stephan M} and {van Horssen}, Jack and Marjolein Ankersmit and Jeroen Meijerink and {van den Tol}, Petrousjka and Steven Oosterling and Jaap Bonjer and Nuray G{\"u}l and {van Egmond}, Marjolein",
year = "2018",
doi = "10.1080/2162402X.2018.1461302",
language = "English",
volume = "7",
pages = "e1461302",
journal = "OncoImmunology",
issn = "2162-4011",
publisher = "Landes Bioscience",
number = "9",

}

Spillage of bacterial products during colon surgery increases the risk of liver metastases development in a rat colon carcinoma model. / Grewal, Simran; Korthouwer, Rianne; Bögels, Marijn; Braster, Rens; Heemskerk, Niels; Budding, Andries E; Pouw, Stephan M; van Horssen, Jack; Ankersmit, Marjolein; Meijerink, Jeroen; van den Tol, Petrousjka; Oosterling, Steven; Bonjer, Jaap; Gül, Nuray; van Egmond, Marjolein.

In: OncoImmunology, Vol. 7, No. 9, 2018, p. e1461302.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Spillage of bacterial products during colon surgery increases the risk of liver metastases development in a rat colon carcinoma model

AU - Grewal, Simran

AU - Korthouwer, Rianne

AU - Bögels, Marijn

AU - Braster, Rens

AU - Heemskerk, Niels

AU - Budding, Andries E

AU - Pouw, Stephan M

AU - van Horssen, Jack

AU - Ankersmit, Marjolein

AU - Meijerink, Jeroen

AU - van den Tol, Petrousjka

AU - Oosterling, Steven

AU - Bonjer, Jaap

AU - Gül, Nuray

AU - van Egmond, Marjolein

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

KW - colorectal tumor surgery

KW - bacterial translocation

KW - macrophages

KW - liver metastases

KW - reactive oxygen species

U2 - 10.1080/2162402X.2018.1461302

DO - 10.1080/2162402X.2018.1461302

M3 - Article

VL - 7

SP - e1461302

JO - OncoImmunology

JF - OncoImmunology

SN - 2162-4011

IS - 9

ER -