Abstract
BACKGROUND: Cisplatin (CDDP)-containing hyperthermic intraperitoneal chemotherapy (HIPEC) is frequently applied in selected patients with peritoneal malignancies derived from ovarian cancer, gastric cancer, and primary peritoneal mesothelioma. HIPEC with CDDP increases perioperative morbidity, in particular by inducing acute kidney injury (AKI). Factors contributing to occurrence of AKI after intraperitoneal perfusion with CDDP have not been sufficiently evaluated. PATIENTS AND METHODS: Data from 63 patients treated with a CDDP-containing HIPEC regimen were retrospectively analyzed concerning demographics, underlying disease, surgery, and HIPEC details to evaluate risk factors of AKI. A preclinical rat perfusion model was applied to assess the influence of temperature, concentration, perfusate volume, perfusion flow rate, and extent of peritonectomy on drug absorption upon intraperitoneal CDDP perfusion. RESULTS: AKI occurred in 66.1% of patients undergoing CDDP-containing HIPEC, with total intraoperative fluid influx being a negative and the extent of parietal peritonectomy being a positive independent predictor of postoperative AKI. In a preclinical model, bilateral anterior parietal peritonectomy significantly increased systemic CDDP absorption by 1.6 to 2-fold. CDDP plasma levels in animals were significantly higher after both perfusion with increased CDDP perfusate concentrations and bilateral anterior parietal peritonectomy. CONCLUSION: CDDP-containing HIPEC is associated with relevant morbidity owing to its systemic toxicity. Extent of parietal peritonectomy is an independent predictor of AKI. CDDP dose reduction should be considered in case of extensive parietal peritonectomy. Cytostatic drug concentrations in HIPEC perfusate should be paid more attention to than total dose per body surface area. Further clinical studies are needed to confirm the presented preclinical findings.