Surgical Endoscopy

, Volume 30, Issue 10, pp 4258–4264 | Cite as

Feasibility of hyperthermic pressurized intraperitoneal aerosol chemotherapy in a porcine model

  • Do Hyun Jung
  • Sang Yong Son
  • Aung Myint Oo
  • Young Suk Park
  • Dong Joon Shin
  • Sang-Hoon Ahn
  • Do Joong Park
  • Hyung-Ho KimEmail author



Peritoneal carcinomatosis is an unmet therapeutic need. Several types of intraperitoneal chemotherapy have been introduced. However, hyperthermic intraperitoneal chemotherapy has limited drug distribution and poor peritoneal penetration. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) does not have the benefits of hyperthermia. We developed a device to apply hyperthermic PIPAC (H-PAC) and evaluated its feasibility in a porcine model.


The device for H-PAC consisted of a laparoscopic aerosol spray and a heater to create hyperthermic capnoperitoneum. We operated on five pigs for the development of the new device and on another five pigs as a survival model. After a pilot experiment of the survival model (Pig A), a hyperthermic pressurized intraperitoneal aerosol of indocyanine green was administered after insertion of three trocars (Pig B) and laparoscopy-assisted distal gastrectomy (LADG) (Pig C) without chemotherapeutic agents. After that, H-PAC with cisplatin was administered after insertion of three trocars (Pig D) and LADG (Pig E). Autopsies were performed on postoperative day 7.


Median operation time was 85 min (80–110 min). Intraperitoneal temperature was constant for 1 h of H-PAC (38.8–40.2 °C). All five pigs were healthy and survived for 7 days. Median weight loss was 0.2 kg. Autopsy tissues of stomach, peritoneum, and jejunum were intact in all five pigs.


H-PAC was feasible and safe in a porcine model.


Hyperthermia Pneumoperitoneum Aerosol Peritoneum therapy Laparoscopic surgery Peritoneal carcinomatosis 



Hyung-Ho Kim has been awarded the research grant from Health Connect which provides health care services through convergence of Seoul National University Hospital and SK Telecom, Korea (Grant No.: 06-2014-158).

Compliance with ethical standards


Do Hyun Jung, Sang Yong Son, Aung Myint Oo, Young Suk Park, Dong Joon Shin, Sang-Hoon Ahn, Do Joong Park, and Hyung-Ho Kim have no conflicts of interest or financial ties to disclose.


  1. 1.
    Yonemura Y, Kawamura T, Bandou E, Tsukiyama G, Endou Y, Miura M (2007) The natural history of free cancer cells in the peritoneal cavity. Recent Results Cancer Res 169:11–23PubMedGoogle Scholar
  2. 2.
    Yonemura Y, Endou Y, Shinbo M, Sasaki T, Hirano M, Mizumoto A, Matsuda T, Takao N, Ichinose M, Mizuno M, Miura M, Ikeda M, Ikeda S, Nakajima G, Yonemura J, Yuuba T, Masuda S, Kimura H, Matsuki N (2009) Safety and efficacy of bidirectional chemotherapy for treatment of patients with peritoneal dissemination from gastric cancer: selection for cytoreductive surgery. J Surg Oncol 100(4):311–316. doi: 10.1002/jso.21324 CrossRefPubMedGoogle Scholar
  3. 3.
    Juhl H, Stritzel M, Wroblewski A, Henne-Bruns D, Kremer B, Schmiegel W, Neumaier M, Wagener C, Schreiber HW, Kalthoff H (1994) Immunocytological detection of micrometastatic cells: comparative evaluation of findings in the peritoneal cavity and the bone marrow of gastric, colorectal and pancreatic cancer patients. Int J Cancer 57(3):330–335CrossRefPubMedGoogle Scholar
  4. 4.
    Japanese Gastric Cancer A (2011) Japanese gastric cancer treatment guidelines 2010 (ver. 3). Gastric Cancer 14(2):113–123. doi: 10.1007/s10120-011-0042-4 CrossRefGoogle Scholar
  5. 5.
    Minchinton AI, Tannock IF (2006) Drug penetration in solid tumours. Nat Rev Cancer 6(8):583–592. doi: 10.1038/nrc1893 CrossRefPubMedGoogle Scholar
  6. 6.
    Roviello F, Caruso S, Neri A, Marrelli D (2013) Treatment and prevention of peritoneal carcinomatosis from gastric cancer by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: overview and rationale. Eur J Surg Oncol 39(12):1309–1316. doi: 10.1016/j.ejso.2013.10.010 CrossRefPubMedGoogle Scholar
  7. 7.
    Yang XJ, Huang CQ, Suo T, Mei LJ, Yang GL, Cheng FL, Zhou YF, Xiong B, Yonemura Y, Li Y (2011) Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy improves survival of patients with peritoneal carcinomatosis from gastric cancer: final results of a phase III randomized clinical trial. Ann Surg Oncol 18(6):1575–1581. doi: 10.1245/s10434-011-1631-5 CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Huang CQ, Yang XJ, Yu Y, Wu HT, Liu Y, Yonemura Y, Li Y (2014) Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy improves survival for patients with peritoneal carcinomatosis from colorectal cancer: a phase II study from a Chinese center. PLoS One 9(9):e108509. doi: 10.1371/journal.pone.0108509 CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Dedrick RL, Flessner MF (1997) Pharmacokinetic problems in peritoneal drug administration: tissue penetration and surface exposure. J Natl Cancer Inst 89(7):480–487CrossRefPubMedGoogle Scholar
  10. 10.
    Solass W, Hetzel A, Nadiradze G, Sagynaliev E, Reymond MA (2012) Description of a novel approach for intraperitoneal drug delivery and the related device. Surg Endosc 26(7):1849–1855. doi: 10.1007/s00464-012-2148-0 CrossRefPubMedGoogle Scholar
  11. 11.
    Solass W, Kerb R, Murdter T, Giger-Pabst U, Strumberg D, Tempfer C, Zieren J, Schwab M, Reymond MA (2014) Intraperitoneal chemotherapy of peritoneal carcinomatosis using pressurized aerosol as an alternative to liquid solution: first evidence for efficacy. Ann Surg Oncol 21(2):553–559. doi: 10.1245/s10434-013-3213-1 CrossRefPubMedGoogle Scholar
  12. 12.
    Tempfer CB, Celik I, Solass W, Buerkle B, Pabst UG, Zieren J, Strumberg D, Reymond MA (2014) Activity of pressurized intraperitoneal aerosol chemotherapy (PIPAC) with cisplatin and doxorubicin in women with recurrent, platinum-resistant ovarian cancer: preliminary clinical experience. Gynecol Oncol 132(2):307–311. doi: 10.1016/j.ygyno.2013.11.022 CrossRefPubMedGoogle Scholar
  13. 13.
    Blanco A, Giger-Pabst U, Solass W, Zieren J, Reymond MA (2013) Renal and hepatic toxicities after pressurized intraperitoneal aerosol chemotherapy (PIPAC). Ann Surg Oncol 20(7):2311–2316. doi: 10.1245/s10434-012-2840-2 CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Kim MC, Choi HJ, Jung GJ, Kim HH (2007) Techniques and complications of laparoscopy-assisted distal gastrectomy (LADG) for gastric cancer. Eur J Surg Oncol 33(6):700–705. doi: 10.1016/j.ejso.2007.02.018 CrossRefGoogle Scholar
  15. 15.
    Solass W, Giger-Pabst U, Zieren J, Reymond MA (2013) Pressurized intraperitoneal aerosol chemotherapy (PIPAC): occupational health and safety aspects. Ann Surg Oncol 20(11):3504–3511. doi: 10.1245/s10434-013-3039-x CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Cascales-Campos PA, Gil J, Gil E, Feliciangeli E, Gonzalez-Gil A, Parrilla JJ, Parrilla P (2014) Treatment of microscopic disease with hyperthermic intraoperative intraperitoneal chemotherapy after complete cytoreduction improves disease-free survival in patients with stage IIIC/IV ovarian cancer. Ann Surg Oncol 21(7):2383–2389. doi: 10.1245/s10434-014-3599-4 CrossRefPubMedGoogle Scholar
  17. 17.
    Fujiwara Y, Takiguchi S, Nakajima K, Miyata H, Yamasaki M, Kurokawa Y, Okada K, Mori M, Doki Y (2011) Neoadjuvant intraperitoneal and systemic chemotherapy for gastric cancer patients with peritoneal dissemination. Ann Surg Oncol 18(13):3726–3731. doi: 10.1245/s10434-011-1770-8 CrossRefPubMedGoogle Scholar
  18. 18.
    Esquivel J, Averbach A, Chua TC (2011) Laparoscopic cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with limited peritoneal surface malignancies: feasibility, morbidity and outcome in an early experience. Ann Surg 253(4):764–768. doi: 10.1097/SLA.0b013e31820784df CrossRefPubMedGoogle Scholar
  19. 19.
    Shin JW, Amar AH, Kim SH, Kwak JM, Baek SJ, Cho JS, Kim J (2014) Complete mesocolic excision with D3 lymph node dissection in laparoscopic colectomy for stages II and III colon cancer: long-term oncologic outcomes in 168 patients. Tech Coloproctol 18(9):795–803. doi: 10.1007/s10151-014-1134-z CrossRefPubMedGoogle Scholar
  20. 20.
    Son SY, Kim HH (2014) Minimally invasive surgery in gastric cancer. World J Gastroenterol 20(39):14132–14141. doi: 10.3748/wjg.v20.i39.14132 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Do Hyun Jung
    • 1
    • 2
  • Sang Yong Son
    • 1
    • 3
  • Aung Myint Oo
    • 1
    • 4
  • Young Suk Park
    • 1
  • Dong Joon Shin
    • 1
  • Sang-Hoon Ahn
    • 1
    • 5
  • Do Joong Park
    • 1
    • 5
  • Hyung-Ho Kim
    • 1
    • 5
    Email author
  1. 1.Department of SurgerySeoul National University Bundang HospitalSeoulKorea
  2. 2.Department of SurgeryKorea University College of MedicineSeoulKorea
  3. 3.Department of SurgeryAjou University School of MedicineSuwonKorea
  4. 4.Department of General SurgeryTan Tock Seng HospitalNovenaSingapore
  5. 5.Department of SurgerySeoul National University College of MedicineSeoulKorea

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