High pressure enhances the effect of hyperthermia in intraperitoneal chemotherapy with oxaliplatin: an experimental study.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) achieve good results in selected patients with peritoneal carcinomatosis. High intra-abdominal pressure could enhance the penetration of chemotherapy drugs. The aim of this study was to compare the effects of high pressure and hyperthermia when used separately and when combined in terms of blood and tissue absorption of oxaliplatin in a swine model of intraperitoneal chemotherapy. METHODS: Four groups of 5 pigs each underwent laparotomy and open intraperitoneal chemotherapy with oxaliplatin at a constant concentration (150 mg/L) for 30 minutes in normothermia and atmospheric pressure (group 1), or hyperthermia (42°C) and atmospheric pressure (group 2), or normothermia and high pressure (25 cm H2O) (group 3), or hyperthermia and high pressure (group 4). High pressure was achieved thorough a water column over the abdomen. Systemic absorption and abdominal tissue mapping of the penetration of oxaliplatin in each group were studied. RESULTS: Blood concentrations of oxaliplatin were similar in the different groups. Hyperthermia achieved higher concentrations in visceral surfaces (P = 0.0014), but not in parietal surfaces. High pressure enhanced diffusion of the drug in both the visceral and parietal peritoneum (P = 0.0058 and P = 0.0044, respectively). The combination of hyperthermia and high pressure significantly increased the penetration of oxaliplatin and achieved the highest tissue concentrations (10.39 mg/kg vs 5.48 mg/kg; P = 0.00001 in the visceral peritoneum, and 66.16 mg/kg vs 35.62 mg/kg; P = 0.0003 in the parietal peritoneum). CONCLUSIONS: Open high-pressure HIPEC with oxaliplatin is feasible in the pig. Hyperthermia enhances diffusion in the visceral peritoneum, whereas high pressure is effective in the visceral and parietal peritoneum. The combination of the two achieves the highest tissue concentrations of oxaliplatin.

Comparison of hyperthermia and adrenaline to enhance the intratumoral accumulation of cisplatin in a murine model of peritoneal carcinomatosis.

BACKGROUND: The best method to deliver intraperitoneal chemotherapy (IPC) for peritoneal carcinomatosis from ovarian cancer is not well defined. The aim of this study was to assess the ability of hyperthermia and adrenaline to enhance the intratumoral accumulation of cisplatin in a rat model of peritoneal carcinomatosis. METHODS: Four groups of 5 BDIX rats with ovarian peritoneal carcinomatosis underwent IPC with 30 mg/l of cisplatin according to the following conditions: normothermia at 37° for 1 or 2 hours, hyperthermia at 42°C for 1 hour or normothermia at 37°C for 2 hours with 2 mg/l adrenaline. Tissue platinum content was measured by atomic absorption spectroscopy. The effect of hyperthermia, adrenaline and the duration of exposure to the drug was measured in vivo (tissue concentration of platinum in tumor, abdominal and extra abdominal tissues) and in vitro (cytotoxicity on human ovarian cancer cells). RESULTS: In vitro, hyperthermia and longer exposure enhanced the accumulation and the cytotoxic effect of cisplatin on cancer cells. In vivo, only the 2 hours treatment with adrenaline resulted in increased platinum concentrations. The rats treated with adrenaline showed significantly lower concentrations of cisplatin in extra peritoneal tissues than those treated with hyperthermia. CONCLUSION: Adrenaline is more effective than hyperthermia in order to enhance the intratumoral concentration of cisplatin in rats with peritoneal carcinomatosis from ovarian origin. It may also decrease the systemic absorption of the drug.

Which method to deliver hyperthermic intraperitoneal chemotherapy with oxaliplatin? An experimental comparison of open and closed techniques.

BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) achieves good results in selected patients with peritoneal carcinomatosis. There are two main procedures to deliver this therapy: the open abdomen and the closed abdomen techniques. A true comparison of the two techniques has never been performed. The aim of this study was to compare blood and abdominal tissue concentrations of oxaliplatin after open and closed techniques to deliver HIPEC. METHODS: Nine pigs underwent HIPEC at 42-43 degrees C for 30 min with oxaliplatin (400 mg/m(2)) according to two techniques: closed (three animals) or open (six animals). The open technique used either an external heater with a pump (three animals) or an intra-abdominal heating cable (three animals) to achieve hyperthermia. Temperature homogeneity, systemic absorption, and abdominal tissue mapping of the penetration of oxaliplatin with each technique were studied. Two additional pigs underwent hyperthermia with dyes instead of oxaliplatin to depict the distribution of the liquid within the abdomen with both techniques. RESULTS: Hyperthermia was satisfactory with both techniques. The closed technique achieved higher temperatures within the diaphragmatic area, while the open technique obtained higher temperatures in the mid and lower abdomen (P < 0.001 for both comparisons). The systemic absorption of oxaliplatin was higher with the open technique (P < 0.04 for all comparisons), as was the accumulation within the abdominal cavity. The operating time for the two techniques was not greatly different. CONCLUSIONS: Intraperitoneal hyperthermia can be achieved with both techniques. The open technique had far higher systemic absorption and abdominal tissue penetration of oxaliplatin than the closed technique.