Top

Published in:

Open Access 01-12-2016 | Translational Research and Biomarkers

In Vivo Feasibility of Electrostatic Precipitation as an Adjunct to Pressurized Intraperitoneal Aerosol Chemotherapy (ePIPAC)

Authors: Tinatin Kakchekeeva, MD, Cedric Demtröder, MD, Nirmitha I. Herath, PhD, Dominic Griffiths, PhD, Jared Torkington, MD, Wiebke Solaß, MD, Marie Dutreix, PhD, Marc A. Reymond, MD, MBA

Published in: Annals of Surgical Oncology | Special Issue 5/2016

Abstract

Background

Intraperitoneal chemotherapy is limited by tissue penetration. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has been shown to improve drug uptake by utilizing the physical properties of gas and pressure. This study investigated the effect of adding electrostatic precipitation to further enhance the pharmacologic properties of this technique.

Methods

A comparative study was performed using an in vivo porcine model. There were 3 cases in each group, PIPAC and electrostatic precipitation pressurized intraperitoneal aerosol chemotherapy (ePIPAC), plus 1 negative control comparing intraperitoneal distribution and tissue uptake of 2 tracer substances (toluidine blue and DT01). Tracer uptake was determined by measuring DT01 in tissue and peritoneal fluid at the end of each procedure.

Results

Electrostatic precipitation of the aerosol was technically feasible in all ePIPAC animals. The aerosol was cleared completely from the visual field within 15 s in the ePIPAC group versus 30 min in the PIPAC group. The peritoneal surface was homogeneously stained in both groups. After 30 min, 1.5 % remaining DT01 was measured in samples of ePIPAC-treated peritoneal fluid versus 15 % in PIPAC animals (p = 0.01). Tissue concentration was increased after ePIPAC versus PIPAC (p = 0.06).

Conclusions

ePIPAC is technically feasible and improves tissue uptake of 2 tracer substances compared to PIPAC by up to tenfold. Intraperitoneal distribution was homogeneous in both groups. ePIPAC has the potential to allow more efficient drug uptake, further dose reduction, a significant shortening of the time required for PIPAC application, and improved health and safety measures.

Available only for authorised users

Minchinton AI, Tannock IF. Drug penetration in solid tumors (review). Nat Rev Cancer. 2006;6:583–92.CrossRefPubMed

Steinert R, Hantschick M, Vieth M, et al. Influence of subclinical tumor spreading on survival after curative surgery for colorectal cancer. Arch Surg. 2008;143:122–8.CrossRefPubMed

Ceelen WP, Flessner MF. Intraperitoneal therapy for peritoneal tumors: biophysics and clinical evidence. Nat Rev Clin Oncol. 2010;7:108–15.CrossRefPubMed

Dedrick RL, Flessner MF. Pharmacokinetic problems in peritoneal drug administration: tissue penetration and surface exposure. J Natl Cancer Inst. 1997;89:480–7.CrossRefPubMed

Reymond MA, Hu B, Garcia A, et al. Feasibility of therapeutic pneumoperitoneum in a large animal model using a microvaporisator. Surg Endosc. 2000;14:51–5.CrossRefPubMed

Haidira A, Pocard M. Nouveau mode d’administration en intrapéritonéal d’une chimiothérapie dans le traitement de la carcinose péritonéale: PIPAC (pressurized intraperitoneal aerosol chemotherapy). Master’s thesis, University of Paris, 2015.

Solaß W, Hetzel A, Nadiradze G, et al. Description of a novel approach for intraperitoneal drug delivery and the related device. Surg Endosc. 2012;26:1849–55.CrossRefPubMed

Solass W, Herbette A, Schwarz T, et al. Therapeutic approach of human peritoneal carcinomatosis with Dbait in combination with capnoperitoneum: proof of concept. Surg Endosc. 2012;26:847–52.CrossRefPubMed

Solass W, Kerb R, Mürdter T, et al. Intraperitoneal chemotherapy of peritoneal carcinomatosis using pressurized aerosol as an alternative to liquid solution: first evidence for efficacy. Ann Surg Oncol. 2014;21:553–9.CrossRefPubMed

10.

Blanco A, Giger-Pabst U, Solass W, Zieren J, Reymond MA. Renal and hepatic toxicities after pressurized intraperitoneal aerosol chemotherapy (PIPAC). Ann Surg Oncol. 2013;20:2311–6.CrossRefPubMedPubMedCentral

11.

Tempfer CB, Celik I, Solass W, et al. Activity of pressurized intraperitoneal aerosol chemotherapy (PIPAC) with cisplatin and doxorubicin in women with recurrent, platinum-resistant ovarian cancer: preliminary clinical experience. Gynecol Oncol. 2014;132:307–11.CrossRefPubMed

12.

Nadiradze G, Giger-Pabst U, Zieren J, Strumberg D, Solass W, Reymond MA. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) with low-dose cisplatin and doxorubicin in gastric peritoneal metastasis. J Gastrointest Surg. 2016;20:367–73.CrossRefPubMed

13.

Demtröder C, Solass W, Zieren J, Strumberg D, Giger-Pabst U, Reymond MA. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) with oxaliplatin in colorectal peritoneal metastasis. Colorectal Dis. 2015. doi:10.1111/codi.13130.

14.

Tempfer CB, Winnekendonk G, Horvat R, et al. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) with cisplatin and doxorubicin in women with recurrent, platinum-resistant ovarian cancer: an open-label, single-arm, phase 2 study (PIPAC-OV1). Gynaecol Oncol. 2015;137:223–8.CrossRef

15.

Croset A, Cordelières FP, Berthault N, et al. Inhibition of DNA damage repair by artificial activation of PARP with siDNA. Nucleic Acids Res. 2013;41:7344–55.CrossRefPubMedPubMedCentral

16.

Ansell J, Warren N, Wall P, et al. Electrostatic precipitation is a novel way of maintaining visual field clarity during laparoscopic surgery: a prospective double-blind randomized controlled pilot study. Surg Endosc. 2014;28:2057–65.CrossRefPubMed

17.

Alesi Surgical, Cardiff, UK. Available at: http://www.alesi-surgical.com/. Accessed April 29, 2015.

18.

Helleday T, Petermann E, Lundin C, Hodgson B, Sharma RA. DNA repair pathways as targets for cancer therapy. Nat Rev Cancer. 2008;8:193–204.CrossRefPubMed

19.

Vasquez KO, Casavant C, Peterson JD. Quantitative whole body biodistribution of fluorescent-labeled agents by non-invasive tomographic imaging. PLoS One. 2011;6:e20594.CrossRefPubMedPubMedCentral

20.

Elias D, Mariani A, Cloutier AS, et al. Modified selection criteria for complete cytoreductive surgery plus HIPEC based on peritoneal cancer index and small bowel involvement for peritoneal carcinomatosis of colorectal origin. Eur J Surg Oncol. 2014;40:1467–73.CrossRefPubMed

21.

Elias D, Goéré D, Dumont F, et al. Role of hyperthermic intraoperative peritoneal chemotherapy in the management of peritoneal metastases. Eur J Cancer. 2014;50:332–40.CrossRefPubMed

22.

Takebayashi K, Sonoda H, Shimizu T, et al. Successful surgical approach for a patient with encapsulating peritoneal sclerosis after hyperthermic intraperitoneal chemotherapy: a case report and literature review. BMC Surg. 2014;14:57.CrossRefPubMedPubMedCentral

23.

Chan WS, Bohmer R, McIntosh R, Blomfield P. Peritoneal fibrosis leading to small bowel obstruction two years after first-line intraperitoneal chemotherapy for optimally debulked ovarian cancer. Aust N Z J Obstet Gynaecol. 2011;51:91–2.CrossRefPubMed

24.

Aihara H, Maruoka H, Kiyozaki H, Konishi F. Sclerosing encapsulating peritonitis (SEP) as a delayed complication of continuous hyperthermic peritoneal perfusion (CHPP): report of a case. Surg Today. 2003;33:232–6.CrossRefPubMed

25.

Vlasveld LT, Taal BG, Kroon BB, Gallee MP, Rodenhuis S. Intestinal obstruction due to diffuse peritoneal fibrosis at 2 years after the successful treatment of malignant peritoneal mesothelioma with intraperitoneal mitoxantrone. Cancer Chemother Pharmacol. 1992;29:405–8.CrossRefPubMed

26.

Wagner P, Boone B, Ramalingam L, et al. Histologic and immunohistochemical alterations associated with cytoreductive surgery and heated intraperitoneal chemotherapy. Ann Surg Oncol. 2015;22(Suppl 3):S588–95.CrossRefPubMed

Title: In Vivo Feasibility of Electrostatic Precipitation as an Adjunct to Pressurized Intraperitoneal Aerosol Chemotherapy (ePIPAC)
Authors: Tinatin Kakchekeeva, MD
Cedric Demtröder, MD
Nirmitha I. Herath, PhD
Dominic Griffiths, PhD
Jared Torkington, MD
Wiebke Solaß, MD
Marie Dutreix, PhD
Marc A. Reymond, MD, MBA
Publication date: 01-12-2016
Publisher: Springer International Publishing
Published in: Annals of Surgical Oncology / Issue Special Issue 5/2016
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-016-5108-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

In Vivo Feasibility of Electrostatic Precipitation as an Adjunct to Pressurized Intraperitoneal Aerosol Chemotherapy (ePIPAC)

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Special Issue 5/2016

Long-Term Survival in Patients with Postoperative Intra-Abdominal Infectious Complications After Curative Gastrectomy for Gastric Cancer: A Propensity Score Matching Analysis

Clinicopathological Features and Prognosis of Mixed-Type T1a Gastric Cancer Based on Lauren’s Classification

Imaging for Quality Control: Comparison of Systematic Video Recording to the Operative Note in Colorectal Cancer Surgery. A Pilot Study

The Half-Life of Serum Des-Gamma-Carboxy Prothrombin Is a Prognostic Index of Survival and Recurrence After Liver Resection for Hepatocellular Carcinoma

Predictors of Surgical Margin Following Breast-Conserving Surgery: A Large Population-Based Cohort Study

The Therapeutic Benefit of Radical Resection for T4b Oral Cavity Squamous Cell Carcinoma with Partial or Complete Response After Radical Chemo-Intensity-Modulated Radiotherapy (IMRT)