Evaluation of a Novel Prototype for Pressurized Intraperitoneal Aerosol Chemotherapy

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.

[1]  Ryan J. Hendrix,et al.  Elevated Maximum Core Body Temperature During Hyperthermic Intraperitoneal Chemoperfusion (HIPEC) is Associated with Increased Postoperative Complications , 2019, Annals of Surgical Oncology.

[2]  M. Hübner,et al.  Pressurised intraperitoneal aerosol chemotherapy: rationale, evidence, and potential indications. , 2019, The Lancet. Oncology.

[3]  M. Stintz,et al.  Technical description of the microinjection pump (MIP®) and granulometric characterization of the aerosol applied for pressurized intraperitoneal aerosol chemotherapy (PIPAC) , 2017, Surgical Endoscopy.

[4]  E. Förster,et al.  Evaluating the Effect of Micropump© Position, Internal Pressure and Doxorubicin Dosage on Efficacy of Pressurized Intra-peritoneal Aerosol Chemotherapy (PIPAC) in an Ex Vivo Model. , 2016, Anticancer research.

[5]  W. Solass,et al.  Pressurized intraperitoneal aerosol chemotherapy with oxaliplatin in colorectal peritoneal metastasis , 2016, Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland.

[6]  E. Förster,et al.  Exploring the Spatial Drug Distribution Pattern of Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) , 2016, Annals of Surgical Oncology.

[7]  W. Solass,et al.  Activity of Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) with cisplatin and doxorubicin in women with recurrent, platinum-resistant ovarian cancer: preliminary clinical experience. , 2014, Gynecologic oncology.

[8]  T. Chua,et al.  Cure for peritoneal metastases? An evidence‐based review , 2013, ANZ journal of surgery.

[9]  Urs Giger-Pabst,et al.  Intraperitoneal Chemotherapy of Peritoneal Carcinomatosis Using Pressurized Aerosol as an Alternative to Liquid Solution: First Evidence for Efficacy , 2013, Annals of Surgical Oncology.

[10]  W. Solass,et al.  Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC): Occupational Health and Safety Aspects , 2013, Annals of Surgical Oncology.

[11]  S. Loibl,et al.  The impact of second to sixth line therapy on survival of relapsed ovarian cancer after primary taxane/platinum-based therapy. , 2012, Annals of oncology : official journal of the European Society for Medical Oncology.

[12]  R. Gill,et al.  Treatment of gastric cancer with peritoneal carcinomatosis by cytoreductive surgery and HIPEC: A systematic review of survival, mortality, and morbidity , 2011, Journal of surgical oncology.

[13]  D. Elias,et al.  Peritoneal colorectal carcinomatosis treated with surgery and perioperative intraperitoneal chemotherapy: retrospective analysis of 523 patients from a multicentric French study. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[14]  P. Morel,et al.  Feasibility of therapeutic pneumoperitoneum in a large animal model using a microvaporisator , 2009, Surgical Endoscopy.

[15]  M. Flessner,et al.  The transport barrier in intraperitoneal therapy. , 2005, American journal of physiology. Renal physiology.

[16]  J. Mcvie,et al.  Direct diffusion of cis-diamminedichloroplatinum(II) in intraperitoneal rat tumors after intraperitoneal chemotherapy: a comparison with systemic chemotherapy. , 1989, Cancer research.

[17]  V. Devita,et al.  Pharmacokinetic rationale for peritoneal drug administration in the treatment of ovarian cancer. , 1978, Cancer treatment reports.