Dynamic Assessment of Local Abdominal Tissue Concentrations of Cisplatin During a HIPEC Procedure: Insights from a Porcine Model.

BACKGROUND

This study aimed to establish a feasible large porcine model for dynamic assessment of cisplatin concentrations in carcinomatosis-relevant abdominal tissues using microdialysis during and after HIPEC combined with cytoreductive surgery.

METHODS

In total, eight pigs underwent open abdominal cytoreductive surgery followed by HIPEC. Microdialysis was employed for dynamic cisplatin concentration sampling in abdominal organs and tissue. Cisplatin dialysate concentrations were analyzed using the UPLC-MS/MS method. STATA (version 18.0) was used to perform a two-compartment model with a zero-order distribution to analyze pharmacokinetic parameters.

RESULTS

Detectable cisplatin concentrations in the evaluated target tissues persisted for at least 6 h post-HIPEC. Higher concentrations were found in superficial tissues; however, the difference was not statistically significant. The cisplatin concentrations were comparable for the stomach, rectum, and liver but higher in the peritoneal lining of the abdominal wall, with the lowest median average peak concentration (Cmax) in the rectum (0.50 µg/mL) and the highest median Cmax in the peritoneum (2.80 µg/mL). No statistically significant differences in cisplatin area under the curve from time zero to the time of the last sample collection (AUC0-last) were found between any of the abdominal compartments except the peritoneal lining of the abdominal wall, which was significantly higher compared with most of the other abdominal tissues {smallest difference; peritoneum 1/liver 2; 1.96 [95% confidence interval (CI) 0.90; 4.26, P = 0.09] and largest difference; peritoneum 3/rectum profound; 4.60 [95% CI 1.94; 10.90, P = 0.001]}.

CONCLUSIONS

Our investigation revealed comparable cisplatin concentrations across abdominal organ surfaces, except higher concentrations in the peritoneal lining of the abdominal wall than in the stomach, rectum, and liver. This model holds promise for future research into HIPEC interventions and anticancer effectiveness.