Paul Dranichnikov: HIPECology: Aspects of Postoperative Morbidity Following the HIPEC Procedure

Abstract

Peritoneal surface malignancy (PM), regardless of the dissemination site, was once considered a terminal condition.  However, the introduction of a surgical approach with cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) with or without early intraperitoneal chemotherapy (EPIC) shifted the attitude from managing the symptoms of PM to disease treatment with curative intent. The magnitude of this combined therapy leaves the patients at risk for a diverse range of postoperative morbidities. Moreover, some small cohort studies argued that combining HIPEC with EPIC is associated with a higher risk of postoperative complications compared to HIPEC alone. The overall aim of the thesis was to investigate postoperative morbidity following the management of PM with CRS and HIPEC ± EPIC.

We investigated readmission morbidity within 6 months after CRS and HIPEC, using a national population-based register. The results of this study showed that morbidity causing HIPEC-related readmission was higher than expected, with almost half of the interventions occurring outside the HIPEC centre. Gastric resection and advanced age are independent predictors of morbidity and readmission. We analyzed postoperative coagulopathy and the risk for venous thromboembolic events (VTE) in a prospective study. Results revealed that significant postoperative changes in coagulation biomarkers occur with dynamic changes over 10 days postoperatively. The incidence of symptomatic VTE was low. Residual tumor at completion of surgery, and elevated D-dimer on day 2, were independent risk factors for postoperative VTE. Postoperative morbidity following HIPEC + EPIC was compared to morbidity following HIPEC alone in our propensity score matched study. Results showed that HIPEC + EPIC is associated with a prolonged hospital stay (LOS), but there was no statistically significant relevant increase in postoperative morbidity, reoperation rate or incidence of readmission. Finally, we also analyzed the impact of different strategies of intraoperative fluid management during CRS and HIPEC on postoperative outcomes. Goal-directed therapy (GDT) is associated with significantly improved LOS despite an increase in morbidity in some patients. GDT management does not affect the postoperative risk for hemorrhage, although the choice of an oxaliplatin-based HIPEC does. Personalized GDT based on patients’ characteristics and surgery should be utilized during the management of CRS and HIPEC patients.