Intraperitoneal chemotherapy (IPC) is a locoregional treatment option in patients with peritoneal metastases (PM). Here, we present an ovarian cancer (OC)-derived PM mouse model for the study of different forms of IPC. Xenograft cell proliferation (luciferase-transfected OVCAR3 and SKOV3 clones) and growth kinetics were assessed using PET scan, bioluminescence imaging (BLI), and histological tumor analysis. Liquid IPC was achieved by intraperitoneal injection with/without capnoperitoneum (6–7 mmHg). Pressurized intraperitoneal aerosol chemotherapy (PIPAC) was mimicked using an intratracheal drug aerosol administration system (micro-nozzle), which, as demonstrated by ex vivo granulometric analysis using laser diffraction spectrometry, produced a polydisperse, bimodal aerosol with a volume-weighted median diameter of (26.49 ± 2.76) µm. Distribution of Tc-99m-labeled doxorubicin in mice was characterized using SPECT and was dependent on the delivery mode and most homogeneous when the micro-nozzle was used. A total of 2 mg doxorubicin per kg body weight was determined to be the optimally effective and tolerable dose to achieve at least 50% tumor reduction. Repeated PIPAC (four times at seven-day-intervals) with doxorubicin in SKOV3-luc tumor-bearing mice resulted in halted tumor proliferation and tumor load reduced after the second round of PIPAC versus controls and the number of tumor nodules was significantly reduced (27.7 ± 9.5 vs. 57.3 ± 9.5; p = 0.0003). Thus, we established the first mouse model of OC PM for the study of IPC using a human xenograft with SKOV3 cells and an experimental IPC setup with a miniaturized nozzle. Repeated IPC was feasible and demonstrated time-dependent anti-tumor activity.
BACKGROUND: In the COVID-19 crisis, laparoscopic surgery is in focus as a relevant source of bioaerosol release. The efficacy of electrostatic aerosol precipitation (EAP) and continuous aerosol evacuation (CAE) to eliminate bioaerosols during laparoscopic surgery was verified. STUDY DESIGN: Ex-vivo laparoscopic cholecystectomies (LCs) were simulated AE EAP or CAE in Pelvitrainer equipped with swine gallbladders. Release of bioaerosols was initiated by performing highfrequency electrosurgery with a monopolar electro hook (MP-HOOK) force at 40 watts (MP-HOOK40) and 60 watts (MP-HOOK60), as well as by ultrasonic cutting (USC). Particle number concentrations (PNC) of arising aerosols were analyzed with a condensation particle counter (CPC). Aerosol samples were taken within the Pelvitrainer close to the source, outside the Pelvitrainer at the working trocar, and in the breathing zone of the surgeon. RESULTS: Within the Pelvitrainer, MP-HOOK40 (6.4 Â 10 5 cm-3) and MP-HOOK60 (7.3 Â 10 5 cm-3) showed significantly higher median PNCs compared to USC (4.4 Â 10 5 cm-3) (p ¼ 0.001). EAP led to a significant decrease of the median PNCs in all 3 groups. A high linear correlation with Pearson correlation coefficients of 0.852, 0.825, and 0.759 were observed by comparing MP-HOOK40 (AE EAP), MP-HOOK60 (AE EAP), and USC (AE EAP), respectively. During ex-vivo LC and CAE, significant bioaerosol contaminations of the operating room occurred. Ex-vivo LC with EAP led to a considerable reduction of the bioaerosol concentration. CONCLUSIONS: EAP was found to be efficient for intraoperative bioaerosol elimination and reducing the risk of bioaerosol exposure for surgical staff.
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