Olivier Facy1, Christophe Combier2, Matthieu Poussier2, Guy Magnin3, Sylvain Ladoire4, François Ghiringhelli4, B Chauffert4, Patrick Rat5, Pablo Ortega-Deballon5. 1. INSERM Unit 866, Equipe Avenir, Dijon, France; Department of Digestive Surgical Oncology, University Hospital, Dijon, France. Electronic address: olivier.facy@chu-dijon.fr. 2. Department of Digestive Surgical Oncology, University Hospital, Dijon, France. 3. Department of Anaesthesiology, University Hospital, Dijon, France. 4. INSERM Unit 866, Equipe Avenir, Dijon, France. 5. INSERM Unit 866, Equipe Avenir, Dijon, France; Department of Digestive Surgical Oncology, University Hospital, Dijon, France.
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. CONCLUSION: 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.
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. CONCLUSION: 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.
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