title: Molecular mechanisms underlying postoperative peritoneal tumor dissemination may differ between a laparotomy and carbon dioxide pneumoperitoneum: a syngeneic mouse model with controlled respiratory support.
abstract: BACKGROUND
  The mechanisms promoting postoperative peritoneal tumor dissemination are unclear. This study aimed to investigate postoperative tumor dissemination over time on both tissue and molecular levels.
  
  
  METHODS
  For this study, C57BL6 mice were randomized into four groups: anesthesia alone (control), carbon dioxide (CO(2)) pneumoperitoneum at low (2 mmHg) or high (8 mmHg) intraperitoneal pressure (IPP), and laparotomy. A mouse ovarian cancer cell line (ID8) was injected intraperitoneally just before surgery. The groups were further subdivided into three groups, and a laparotomy was performed to evaluate tumor dissemination on postoperative day (POD) 7, 14, or 42.
  
  
  RESULTS
  The incidence of cancer cell invasion into the muscle layers of the abdominal wall was significantly higher in the laparotomy and high-IPP groups than in the low-IPP and control groups on PODs 7 and 42. Expression levels of beta 1 integrin, cMet, urokinase-type plasminogen activator (uPA), urokinase-type plasminogen activator receptor (uPAR), and type-1 plasminogen activator inhibitor (PAI-1) mRNA in the disseminated nodules were not significantly different among the four groups on POD 7. However, the expression levels of all these genes in the disseminated nodules in the laparotomy group were significantly higher on POD 14 than on POD 7. They then returned to control levels on POD 42. There were no significant differences in the expression levels of any of these genes among the groups on POD 42.
  
  
  CONCLUSIONS
  The current study suggests that the molecular mechanisms underlying postoperative peritoneal tumor dissemination may differ between a laparotomy and CO(2) pneumoperitoneum. Therefore, strategies targeting postoperative tumor dissemination likely will need to account for the surgical environment.
authors.affiliation: Université d'Auvergne-Clermont I, Centre d'Endoscopie et des Nouvelles Techniques Interventionnelles, Clermont-Ferrand, France. sachikoma@aol.com
authors.forename: Sachiko
authors.initials: S
authors.lastname: Matsuzaki
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bourdel
authors.forename: Claude
authors.initials: C
authors.lastname: Darcha
authors.forename: Pierre J
authors.initials: PJ
authors.lastname: Déchelotte
authors.forename: Jean-Etienne
authors.initials: JE
authors.lastname: Bazin
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Pouly
authors.forename: Gérard
authors.initials: G
authors.lastname: Mage
authors.forename: Michel
authors.initials: M
authors.lastname: Canis
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics*; D045744:Cell Line, Tumor; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D019012:Integrin beta1 / Q000096:biosynthesis / Q000235:genetics; D007813:Laparotomy / Q000009:adverse effects* / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D009366:Neoplasm Seeding; D009374:Neoplasms, Experimental; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D010052:Ovariectomy / Q000009:adverse effects / Q000379:methods; D010534:Peritoneal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D010537:Peritoneum / Q000378:metabolism / Q000473:pathology; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis / Q000235:genetics; D011028:Pneumoperitoneum, Artificial / Q000009:adverse effects* / Q000379:methods; D016133:Polymerase Chain Reaction; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics*; D055293:Receptors, Urokinase Plasminogen Activator / Q000096:biosynthesis / Q000235:genetics; D012121:Respiration, Artificial / Q000379:methods; D013997:Time Factors; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D019012:Integrin beta1; D017395:Plasminogen Activator Inhibitor 1; D012334:RNA, Neoplasm; D055293:Receptors, Urokinase Plasminogen Activator; D019859:Proto-Oncogene Proteins c-met; D014568:Urokinase-Type Plasminogen Activator