title: Laparoscopic environmental changes during surgery enhance the invasive potential of tumours.
abstract: OBJECTIVE
  The use of laparoscopic techniques in resection of malignant tumours has been proposed to offer potential benefit to the patient in the form of earlier recovery and less immune paresis; however, reported tumour seeding, both peritoneal and at port site, has put this approach into question. The biological effects of the introduction of carbon dioxide or helium to form a pneumoperitoneum on tumour invasion and dissemination are unknown.
  
  
  METHODS
  A human colonic adenocarcinoma cell line (SW1222) was exposed to in vitro laparoscopic environment of either carbon dioxide or helium for 4 h, mimicking the duration of a laparoscopic colorectal resection. Alteration in production of matrix metalloproteinase (MMP)-2, MMP-9 and urokinase-type plasminogen activator (uPA) due to exposure to a laparoscopic environment was determined by zymography and correlated to invasive capacity by a standard Matrigel-based invasion assay. Incorporation of specific gelatinase inhibitors or antibodies directed at the uPA receptor was utilized to determine the relative importance of proteases.
  
  
  RESULTS
  Exposure to the laparoscopic environment significantly enhanced production of the proteases MMP-2, MMP-9 and uPA. A concomitant enhancement of invasive capacity was also observed, being blocked by specific protease inhibitors. Changes in both protease production and aggression were observable for at least 24 h following the removal of the operative environment, indicating the possible long-term effects of the initial insult.
  
  
  CONCLUSIONS
  Exposure to the laparoscopic environment enhances the invasive capacity of colonic adenocarcinomas via a well-defined protease-determined pathway. It therefore appears likely that tumour cells released into the operative field can be made increasingly aggressive by a laparoscopic operative environment and can thus contribute to disease dissemination.
authors.affiliation: Department of Surgical Technology and Oncology, Division of Surgery, Anaesthetics and Intensive Care, Imperial College of Science, Technology and Medicine, St. Mary's Hospital, London, UK. p.paraskevas@ic.ac.uk
authors.forename: P A
authors.initials: PA
authors.lastname: Paraskeva
authors.forename: P F
authors.initials: PF
authors.lastname: Ridgway
authors.forename: T
authors.initials: T
authors.lastname: Jones
authors.forename: A
authors.initials: A
authors.lastname: Smith
authors.forename: D H
authors.initials: DH
authors.lastname: Peck
authors.forename: A W
authors.initials: AW
authors.lastname: Darzi
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D002245:Carbon Dioxide / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D006371:Helium / Q000378:metabolism; D006801:Humans; D010535:Laparoscopy / Q000009:adverse effects*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000473:pathology*; D011028:Pneumoperitoneum, Artificial; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D002245:Carbon Dioxide; D006371:Helium; D014568:Urokinase-Type Plasminogen Activator; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9