Abstract | OBJECTIVE: To investigate the role of increased intra-abdominal pressure (IAP) on the intratumoral accumulation and the antitumor effect of intraperitoneal cisplatin in rats with advanced peritoneal carcinomatosis. To evaluate the tolerance of IAP in pigs, as it is a large animal with a body size equivalent to humans. SUMMARY BACKGROUND DATA: To investigate if an active convection, driven by a positive IAP, increases cisplatin penetration and antitumor effectiveness in a model of advanced peritoneal carcinomatosis in rats. EXPERIMENTAL DESIGN: RESULTS: The maximum tolerated IAP was 22 mm Hg for 1 hour in nonventilated rats. IAP, in comparison with IV or conventional IP injections, resulted in the increased concentration and depth of diffusion of platinum into diaphragm and peritoneal tumor nodules. Consequently, IAP treatment induced an extended survival of rats treated at an advanced stage of carcinomatosis. In 7 50- to 70-kg ventilated pigs, a 40-mm Hg IAP was well tolerated when maintained stable for 2 hours. Renal failure occurred in pigs receiving a total dose of 200 and 400 mg of cisplatin with IAP, but a dose of 100 mg was well tolerated. CONCLUSIONS: Intraperitoneal chemotherapy with increased IAP, in comparison with conventional IP or IV chemotherapy, improved the tumor accumulation and the antitumor effect of cisplatin in rats bearing advanced peritoneal carcinomatosis. In preclinical conditions, the tolerance of sustained IAP was manageable in ventilated pigs.
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Authors | Philippe Esquis, David Consolo, Guy Magnin, Philippe Pointaire, Philippe Moretto, Maria Dolores Ynsa, Jean-Luc Beltramo, Carole Drogoul, Michel Simonet, Laurent Benoit, Patrick Rat, Bruno Chauffert |
Journal | Annals of surgery
(Ann Surg)
Vol. 244
Issue 1
Pg. 106-12
(Jul 2006)
ISSN: 0003-4932 [Print] United States |
PMID | 16794395
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Cisplatin
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Topics |
- Abdomen
(physiology)
- Animals
- Antineoplastic Agents
(administration & dosage, pharmacokinetics)
- Carcinoma
(mortality, pathology)
- Cisplatin
(administration & dosage, pharmacokinetics)
- Female
- Infusions, Parenteral
- Injections, Intraperitoneal
- Male
- Peritoneal Neoplasms
(mortality, pathology)
- Pressure
- Rats
- Rats, Inbred Strains
- Spectrophotometry, Atomic
- Survival Rate
- Swine
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