Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has been suggested as an alternative option for treating peritoneal carcinomatosis (PC). Even with its clinical advantages, the current PIPAC system still suffers from limitations regarding drug distribution area and penetration depth. Thus, we evaluated the new PIPAC system using a novel prototype, and compared its performance to the results from previous studies related with the current MIP® indirectly because the system is currently not available for purchase in the market. The developed prototype includes a syringe pump, a nozzle, and controllers. Drug distribution was conducted using a methylene blue solution for performance test. For penetration depth evaluation, an ex-vivo experiment was performed with porcine tissues in a 3.5 L plastic box. Doxorubicin was sprayed using the novel prototype, and its penetration depth was investigated by confocal laser scanning microscopy. The experiment was repeated with varying nozzle levels from the bottom. The novel prototype sprays approximately 30 μm drug droplets at a flow rate of 30 mL/min with 7 bars of pressure. The average diameter of sprayed region with concentrated dye was 18.5 ± 1.2 cm, which was comparable to that of the current MIP® (about 10 cm). The depth of concentrated diffusion (DCD) did not differ among varying nozzle levels, whereas the depth of maximal diffusion (DMD) decreased with increasing distance between the prototype and the bottom (mean values, 515.3 μm at 2 cm; 437.6 μm at 4 cm; 363.2 μm at 8 cm), which was comparable to those of the current MIP® (about 350–500 μm). We developed a novel prototype that generate small droplets for drug aerosolization and that have a comparably wide sprayed area and depth of penetration to the current MIP® at a lower pressure.

This study aims to evaluate the drug distribution, tissue concentrations, penetration depth, pharmacokinetic properties, and toxicities after rotational intraperitoneal pressurized aerosol chemotherapy (RIPAC) in pigs. Because relevant medical devices have not been introduced, we developed our prototype of pressurized intraperitoneal aerosol chemotherapy (PIPAC) and RIPAC by adding a conical pendulum motion device for rotating the nozzle. RIPAC and PIPAC were conducted using 150 ml of 1% methylene blue to evaluate the drug distribution and 3.5 mg of doxorubicin in 50 ml of 0.9% NaCl to evaluate the tissue concentrations and penetration depth, pharmacokinetic properties, and toxicities. All agents were sprayed as aerosols via the nozzle, DreamPen ® (Dalim Biotech, Gangwon, South Korea), with a velocity of 5 km/h at a flow rate of 30 ml/min under a pressure of 7 bars, and capnoperitoneum of 12 mmHg was maintained for 30 min. As a result, RIPAC showed a wider distribution and stronger intensity than PIPAC. Compared with PIPAC, RIPAC demonstrated high values of the tissue concentration in the central, right upper, epigastrium, left upper, left lower, right lower, and right flank regions (median, 375.5–2124.9 vs. 161.7–1240 ng/ml; p ≤ .05), and higher values of the depth of concentrated diffusion and depth of maximal diffusion (median, 232.5–392.7 vs. 116.9–240.1 μm; 291.2–551.2 vs. 250.5–362.4 μm; p ≤ .05) in all regions except for bowels. In RIPAC, the pharmacokinetic properties reflected hemodynamic changes during capnoperitoneum, and there were no related toxicities. Conclusively, RIPAC may have the potential to enhance drug delivery into the peritoneum compared to PIPAC.

Objectives To investigate the impact of computed tomography (CT)-based, artificial intelligence-driven waist skeletal muscle volume on survival outcomes in patients with endometrial cancer. Methods We retrospectively identified endometrial cancer patients who received primary surgical treatment between 2014 and 2018 and whose pre-treatment CT scans were available (n = 385). Using an artificial intelligence-based tool, the skeletal muscle area (cm2) at the third lumbar vertebra (L3) and the skeletal muscle volume (cm3) at the waist level were measured. These values were converted to the L3 skeletal muscle index (SMI) and volumetric SMI by normalisation with body height. The relationships between L3, volumetric SMIs, and survival outcomes were evaluated. Results Setting 39.0 cm2/m2 of L3 SMI as cut-off value for sarcopenia, sarcopenia (< 39.0 cm2/m2, n = 177) and non-sarcopenia (≥ 39.0 cm2/m2, n = 208) groups showed similar progression-free survival (PFS; p = 0.335) and overall survival (OS; p = 0.241). Using the median value, the low-volumetric SMI group (< 206.0 cm3/m3, n = 192) showed significantly worse PFS (3-year survival rate, 77.3% vs. 88.8%; p = 0.004) and OS (3-year survival rate, 92.8% vs. 99.4%; p = 0.003) than the high-volumetric SMI group (≥ 206.0 cm3/m3, n = 193). In multivariate analyses adjusted for baseline body mass index and other factors, low-volumetric SMI was identified as an independent poor prognostic factor for PFS (adjusted HR, 1.762; 95% CI, 1.051–2.953; p = 0.032) and OS (adjusted HR, 5.964; 95% CI, 1.296–27.448; p = 0.022). Conclusions Waist skeletal muscle volume might be a novel prognostic biomarker in patients with endometrial cancer. Assessing body composition before treatment can provide important prognostic information for such patients.

For recurrent ovarian, fallopian or primary peritoneal cancer with peritoneal carcinomatosis (PC), it is challenging to resect tumors completely or to get complete remission by intravenous (IV) chemotherapy, and many patients show the resistance to various chemotherapeutic agents for IV chemotherapy ultimately.As an alternative, pressurized intraperitoneal aerosol chemotherapy (PIPAC) has been introduced for treating the disease, which delivers chemotherapeutic agents as an aerosol form while maintaining high intraperitoneal (IP) pressure. Based on preclinical studies, PIPAC showed better penetration depth and distribution of drugs into the peritoneum in comparison to conventional IP chemotherapy. Tumor regression on histology and peritoneal carcinomatosis index (PCI) has also been shown in relevant studies. In addition, most of the PIPAC procedures were completed successfully with acceptable toxicity due to the use of a low dose of chemotherapeutic agents. For considering these advantages of PIPAC, we review the current status of PIPAC for treating recurrent ovarian, fallopian or primary peritoneal cancer through literature review.

Background Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has been introduced as palliative therapy for treating peritoneal metastasis (PM) of solid tumors. However, restricted use in the limited countries and the uneven distribution and penetration in various regions of the peritoneal cavity ac as disadvantages of PIPAC. Thus, the KOrean Rotational Intraperitoneal pressurized Aerosol chemotherapy (KORIA) trial group developed rotational intraperitoneal pressurized aerosol chemotherapy (RIPAC) for enhancing drug delivery into the peritoneum to treat PM, and evaluated the drug distribution, tissue concentrations, penetration depth, pharmacokinetic properties, and toxicities after RIPAC with doxorubicin in pigs. Methods For delivering doxorubicin as aerosols, we used our prototype for PIPAC, which sprayed about 30-µm sized droplets through the nozzle. The mean diameter of the sprayed region was 18.5 cm, and the penetration depth ranged from 360 to 520 µm, comparable to the microinjection pump (Capnopen®; Capnomed, Villingendorf, Germany). For RIPAC, a conical pendulum motion device was added to PIPAC for rotating the nozzle. RIPAC and PIPAC were conducted using 150 ml of 1% methylene blue to evaluate drug distribution and 3.5 mg of doxorubicin in 50 ml of 0.9% NaCl to evaluate tissue concentration and penetration depth, pharmacokinetic properties, and toxicities. All agents were sprayed as aerosols via the nozzle with a velocity of 5 km/h at a flow rate of 30 ml/min under a pressure of 7 bars, and capnoperitoneum of 12 mmHg was maintained for 30 minutes. As a control, we conducted early postoperative intraperitoneal chemotherapy (EPIC) using 1% methylene blue solution with an infusion flow rate of 100 ml/min for 30 minutes and the drainage of 1 L every 10 minutes. Results RIPAC showed a wider distribution and stronger intensity than EPIC and PIPAC. Moreover, the tissue concentration and penetration depth of doxorubicin were higher in RIPAC than in PIPAC. In RIPAC, the pharmacokinetic properties reflected hemodynamic changes during capnoperitoneum, and there were no renal and hepatic toxicities related to RIPAC using doxorubicin. Conclusions RIPAC may have the potential to enhance drug delivery into the peritoneum compared to PIPAC.