Chemical/technical risk analysis of a new multidirectional nebulizer (MDN) and its clinical implementation for the safe administration of Pressurized Intraperitoneal Aerosol Chemotherapy (MDN-PIPAC)

Abstract

Background/Aim: To test the chemoresistance of a multi-directional nebulizer (MDN) and to establish and implement a perioperative clinical safety concept for its clinical use to deliver pressurised intraperitoneal aerosol chemotherapy (MDN-PIPAC). Study design: Ex-vivo nebulization of cytostatic drugs with the MDN device to assess chemoresistance/toxicological risks. Establishment of a perioperative safety concept for the clinical administration of MDN-PIPAC by ex- and in-vivo porcine simulation studies. Consecutive unicentric case series of 30 MDN-PIPACs in patients with peritoneal surface malignancies (PSM). Endpoints were intraoperative adverse events and perioperative complications (Clavien-Dindo). Results: Toxicological studies/risk assessment confirm the safety of administering PIPAC with the MDN. The horizontal nozzles must protrude at least 7 mm beyond the most distal end of the trocar tip and lateral tilting should be prevented by fixation of the device in a single-arm holder. A total of 21 patients (male/female ratio: 2:1) with a mean age of 62 (range: 38-86) years underwent 30 consecutive MDN-PIPACs for peritoneal surface malignancies of different origin. ECOG 0 and 1 were seen in five and 16 patients, respectively. Thirteen, seven and one patient underwent one, two and three MDN-PIPACs, respectively. Two patients received only one cycle of MDN-PIPAC because they were considered candidates for cytoreductive surgery and heated intraperitoneal chemotherapy. There were no intraoperative technical/medical problems observed. Four patients suffered from postoperative grade I complications. Conclusions: Compounds leached during chemotherapy nebulization with the MDN are toxicologically safe. MDN-PIPAC administration is safe and the postoperative course comparable to that of the conventional PIPAC nebulizer.