title: High pressure does not counterbalance the advantages of open techniques over closed techniques during heated intraperitoneal chemotherapy with oxaliplatin.
abstract: BACKGROUND
  Heated intraperitoneal chemotherapy (HIPEC) treats residual microscopic disease after cytoreductive surgery. In experimental models, the open HIPEC technique has shown a higher and more homogenous concentration of platinum in the peritoneum than achieved using the closed technique. A 25-cm H2O pressure enhances the penetration of oxaliplatin. Because pressure is easier to set up with the closed technique, high pressure may counterbalance the drawbacks of this technique versus open HIPEC, and a higher pressure may induce a higher penetration. Because higher concentration does not mean deeper penetration, a study of tissues beneath the peritoneum is required. Finally, achieving a deeper penetration (and a higher concentration) raises the question of the passage of drugs through the surgical glove and the surgeon's safety.
  
  
  METHODS
  Four groups of pigs underwent HIPEC with oxaliplatin (150 mg/L) for 30 minutes in open isobaric pressure and pressure at 25 cm H2O, and closed pressure at 25 and 40 cm H2O. Systemic absorption and peritoneal mapping of the concentration of platinum were analyzed, as well as in the retroperitoneal tissue and the surgical gloves.
  
  
  RESULTS
  Blood concentrations were higher in open groups. In the parietal surfaces, the concentrations were not different between the isobaric and the closed groups (47.08, 56.39, and 48.57 mg/kg, respectively), but were higher in the open high-pressure group (85.93 mg/kg). In the visceral surfaces, they were lower in the closed groups (3.2 and 3.05 mg/kg) than in the open groups (7.03 and 9.56 mg/kg). Platinum concentrations were similar in the deep retroperitoneal tissue when compared between isobaric and high-pressure procedures. No platin was detected in the internal aspect of the gloves.
  
  
  CONCLUSIONS
  The use of high pressure during HIPEC does not counterbalance the drawbacks of closed techniques. The tissue concentration of oxaliplatin achieved with the open techniques is higher, even if high pressure is applied during a closed technique. Open 25 cm H2O HIPEC achieved the highest tissue penetration of oxaliplatin, but did not enhance the depth of oxaliplatin penetration. High pressure did not enhance the risk of HIPEC.
authors.affiliation: INSERM Unit 866, Equipe Avenir, Dijon, France; Department of Digestive Surgical Oncology, University Hospital, Dijon, France. Electronic address: olivier.facy@chu-dijon.fr.
authors.forename: Olivier
authors.initials: O
authors.lastname: Facy
authors.affiliation: Department of Digestive Surgical Oncology, University Hospital, Dijon, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Combier
authors.affiliation: Department of Digestive Surgical Oncology, University Hospital, Dijon, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Poussier
authors.affiliation: Department of Anaesthesiology, University Hospital, Dijon, France.
authors.forename: Guy
authors.initials: G
authors.lastname: Magnin
authors.affiliation: INSERM Unit 866, Equipe Avenir, Dijon, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Ladoire
authors.affiliation: INSERM Unit 866, Equipe Avenir, Dijon, France.
authors.forename: François
authors.initials: F
authors.lastname: Ghiringhelli
authors.affiliation: INSERM Unit 866, Equipe Avenir, Dijon, France.
authors.forename: B
authors.initials: B
authors.lastname: Chauffert
authors.affiliation: INSERM Unit 866, Equipe Avenir, Dijon, France; Department of Digestive Surgical Oncology, University Hospital, Dijon, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Rat
authors.affiliation: INSERM Unit 866, Equipe Avenir, Dijon, France; Department of Digestive Surgical Oncology, University Hospital, Dijon, France.
authors.forename: Pablo
authors.initials: P
authors.lastname: Ortega-Deballon
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005260:Female; D006439:Hemodynamics; D006358:Hot Temperature; D007263:Infusions, Parenteral / Q000379:methods*; D007813:Laparotomy; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000077150:Oxaliplatin; D011312:Pressure; D013552:Swine
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin