Archives of Gynecology and Obstetrics

, Volume 297, Issue 4, pp 837–846 | Cite as

The use of PIPAC (pressurized intraperitoneal aerosol chemotherapy) in gynecological oncology: a statement by the German “Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR)”, the Swiss and Austrian AGO, and the North-Eastern German Society of Gynaecologic Oncology

  • A. M. DueckelmannEmail author
  • D. Fink
  • P. Harter
  • V. Heinzelmann
  • C. Marth
  • M. Mueller
  • A. Reinthaller
  • K. Tamussino
  • P. Wimberger
  • J. Sehouli



Ovarian, tubal, and peritoneal carcinomas primarily affect the peritoneal cavity, and they are typically diagnosed at an advanced tumor stage (Foley, Rauh-Hain, del Carmen in Oncology (Williston Park) 27:288–294, 2013). In the course of primary surgery, postoperative tumor residuals are, apart from the tumor stage, the strongest independent factors of prognosis (du Bois, Reuss, Pujade-Lauraine, Harter, Ray-Coquard, Pfisterer in Cancer 115:1234–1244, 2009). Due to improved surgical techniques, including the use of multi-visceral procedures, macroscopic tumor clearance can be achieved in oncological centers, in most cases (Harter, Muallem, Buhrmann et al in Gynecol Oncol 121:615–619, 2011). However, to date, it has not been shown that peritoneal carcinomatosis is, per se, an independent factor of prognosis or that it excludes the achievement of tumor clearance. Several studies have shown that a preceding drug therapy in peritoneal carcinomatosis could positively influence the overall prognosis (Trimbos, Trimbos, Vergote et al in J Natl Cancer Inst 95:105–112, 2003). In relapses of ovarian carcinoma, studies have shown that peritoneal carcinomatosis is a negative predictor of complete tumor resection; however, when it is possible to resect the tumor completely, peritoneal carcinomatosis does not play a role in the prognosis (Harter, Hahmann, Lueck et al in Ann Surg Oncol 16:1324–1330, 2009).


PIPAC is a highly experimental method for treating patients with ovarian, tubal, and peritoneal cancer. To date, only three studies have investigated a total of 184 patients with peritoneal carcinomatosis (Grass, Vuagniaux, Teixeira-Farinha, Lehmann, Demartines, Hubner in Br J Surg 104:669–678, 2017). Only some of those studies were phase I/II studies that included PIPAC for patients with different indications and different cancer entities. It is important to keep in mind that the PIPAC approach is associated with relatively high toxicity. To date, no systematic dose-finding studies have been reported. Moreover, no studies have reported improvements in progression-free or overall survival associated with PIPAC therapy.


Randomized phase III studies are required to evaluate the effect of this therapy compared to other standard treatments (sequential or simultaneous applications with systemic chemotherapy). In cases of ovarian, tubal, and peritoneal cancer, PIPAC should not be performed outside the framework of prospective, controlled studies.


PIPAC Ovarian cancer Peritoneal cancer Tubal cancer Therapy Chemotherapy 


Author contributions

AMD: manuscript writing. DF: manuscript editing. PH: manuscript editing, project development. VH: manuscript editing. CM: manuscript editing. MM: manuscript editing. AR manuscript editing. KT: manuscript editing. PW: manuscript editing, project development. JS: manuscript writing, project development

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest.


This study was not funded.

Human and animal participants

This article does not contain any studies with human participants or animals performed by any of the authors.


  1. 1.
    Ferlay J, Soerjomataram I, Dikshit R et al (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136:E359–E386CrossRefPubMedGoogle Scholar
  2. 2.
    Foley OW, Rauh-Hain JA, del Carmen MG (2013) Recurrent epithelial ovarian cancer: an update on treatment. Oncology (Williston Park) 27(288–94):98Google Scholar
  3. 3.
    du Bois A, Reuss A, Pujade-Lauraine E, Harter P, Ray-Coquard I, Pfisterer J (2009) Role of surgical outcome as prognostic factor in advanced epithelial ovarian cancer: a combined exploratory analysis of 3 prospectively randomized phase 3 multicenter trials: by the Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR) and the Groupe d’Investigateurs Nationaux Pour les Etudes des Cancers de l’Ovaire (GINECO). Cancer 115:1234–1244CrossRefPubMedGoogle Scholar
  4. 4.
    Griffiths CT, Fuller AF (1978) Intensive surgical and chemotherapeutic management of advanced ovarian cancer. Surg Clin North Am 58:131–142CrossRefPubMedGoogle Scholar
  5. 5.
    Harter P, Muallem ZM, Buhrmann C et al (2011) Impact of a structured quality management program on surgical outcome in primary advanced ovarian cancer. Gynecol Oncol 121:615–619CrossRefPubMedGoogle Scholar
  6. 6.
    Bristow RE, Tomacruz RS, Armstrong DK, Trimble EL, Montz FJ (2002) Survival effect of maximal cytoreductive surgery for advanced ovarian carcinoma during the platinum era: a meta-analysis. J Clin Oncol 20:1248–1259CrossRefPubMedGoogle Scholar
  7. 7.
    Stuart GC, Kitchener H, Bacon M et al (2011) 2010 Gynecologic Cancer InterGroup (GCIG) consensus statement on clinical trials in ovarian cancer: report from the Fourth Ovarian Cancer Consensus Conference. Int J Gynecol Cancer 21:750–755CrossRefPubMedGoogle Scholar
  8. 8.
    Ledermann JA, Harter P, Gourley C et al (2016) Overall survival in patients with platinum-sensitive recurrent serous ovarian cancer receiving olaparib maintenance monotherapy: an updated analysis from a randomised, placebo-controlled, double-blind, phase 2 trial. Lancet Oncol 17:1579–1589CrossRefPubMedGoogle Scholar
  9. 9.
    Armstrong DK, Bundy B, Wenzel L et al (2006) Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med 354:34–43CrossRefPubMedGoogle Scholar
  10. 10.
    Gadducci A, Conte PF (2008) Intraperitoneal chemotherapy in the management of patients with advanced epithelial ovarian cancer: a critical review of the literature. Int J Gynecol Cancer 18:943–953CrossRefPubMedGoogle Scholar
  11. 11.
    Wenzel L et al (2016) Patient-reported outcomes of a phase III clinical trial of bevacizumab with IV versus IP chemotherapy in ovarian, fallopian tube, and primary peritoneal carcinoma. NCI-supplied agent: bevacizumab. NCT011o67712, a GOG/NRG trial. SGO 2016; Abstract 7Google Scholar
  12. 12.
    Walker JL et al (2016) A phase III clinical trial of bevacizumab with IV versus IP chemotherapy in ovarian, fallopian tube, and primary peritoneal carcinoma. NCI-supplied agent: bevacizumab. NCT01167712, a GOG/NRG trial (GOG 252). SGO 2016; Abstract 6 2016Google Scholar
  13. 13.
    Reymond MA, Hu B, Garcia A et al (2000) Feasibility of therapeutic pneumoperitoneum in a large animal model using a microvaporisator. Surg Endosc 14:51–55CrossRefPubMedGoogle Scholar
  14. 14.
    Solass W, Giger-Pabst U, Zieren J, Reymond MA (2013) Pressurized intraperitoneal aerosol chemotherapy (PIPAC): occupational health and safety aspects. Ann Surg Oncol 20:3504–3511CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Oyais ASW, Zieren J, Reymond MA, Giger-Pabst U (2016) Arbeitssicherheitsaspekte der intraperitonealen Druck-Aerosol-Chemotherapie (PIPAC): Bestätigung der Unbedenklichkeit. Zentralbl Chir 141(4):421–424PubMedGoogle Scholar
  16. 16.
    Hubner M, Teixeira Farinha H, Grass F et al (2017) Feasibility and safety of pressurized intraperitoneal aerosol chemotherapy for peritoneal carcinomatosis: a retrospective cohort study. Gastroenterol Res Pract 2017:6852749CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    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 26:1849–1855CrossRefPubMedGoogle Scholar
  18. 18.
    Solass W, Herbette A, Schwarz T et al (2012) Therapeutic approach of human peritoneal carcinomatosis with Dbait in combination with capnoperitoneum: proof of concept. Surg Endosc 26:847–852CrossRefPubMedGoogle Scholar
  19. 19.
    Solass WKR, Mürdter 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 21:553–559CrossRefPubMedGoogle Scholar
  20. 20.
    Dedrick RL, Flessner MF (1997) Pharmacokinetic problems in peritoneal drug administration: tissue penetration and surface exposure. J Natl Cancer Inst 89:480–487CrossRefPubMedGoogle Scholar
  21. 21.
    Heldin CH, Rubin K, Pietras K, Ostman A (2004) High interstitial fluid pressure—an obstacle in cancer therapy. Nat Rev Cancer 4:806–813CrossRefPubMedGoogle Scholar
  22. 22.
    Bellendorf A, Khosrawipour V, Khosrawipour T et al (2018) Scintigraphic peritoneography reveals a non-uniform 99mTc-Pertechnetat aerosol distribution pattern for Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) in a swine model. Surg Endosc 32(1):166–174CrossRefPubMedGoogle Scholar
  23. 23.
    Gohler D, Khosrawipour V, Khosrawipour T et al (2017) Technical description of the microinjection pump (MIP(R)) and granulometric characterization of the aerosol applied for pressurized intraperitoneal aerosol chemotherapy (PIPAC). Surg Endosc 31(4):1778–1784CrossRefPubMedGoogle Scholar
  24. 24.
    Khosrawipour V, Khosrawipour T, Falkenstein TA et al (2016) Evaluating the effect of micropump(c) position, internal pressure and doxorubicin dosage on efficacy of pressurized intra-peritoneal aerosol chemotherapy (PIPAC) in an ex vivo model. Anticancer Res 36:4595–4600CrossRefPubMedGoogle Scholar
  25. 25.
    Khosrawipour V, Khosrawipour T, Kern AJ et al (2016) Distribution pattern and penetration depth of doxorubicin after pressurized intraperitoneal aerosol chemotherapy (PIPAC) in a postmortem swine model. J Cancer Res Clin Oncol 142:2275–2280CrossRefPubMedGoogle Scholar
  26. 26.
    Esquis P, Consolo D, Magnin G et al (2006) High intra-abdominal pressure enhances the penetration and antitumor effect of intraperitoneal cisplatin on experimental peritoneal carcinomatosis. Ann Surg 244:106–112CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Jacquet P, Stuart OA, Chang D, Sugarbaker PH (1996) Effects of intra-abdominal pressure on pharmacokinetics and tissue distribution of doxorubicin after intraperitoneal administration. Anticancer Drugs 7:596–603CrossRefPubMedGoogle Scholar
  28. 28.
    Khosrawipour VBA, Khosrawipour C, Hedayat-Pour Y et al (2016) Irradiation does not increase the penetration depth of doxorubicin in normal tissue after pressurized intra-peritoneal aerosol chemotherapy (PIPAC) in an ex vivo model. In Vivo 30:593–597PubMedGoogle Scholar
  29. 29.
    Khosrawipour V, Khosrawipour T, Hedayat-Pour Y et al (2017) Effect of whole-abdominal irradiation on penetration depth of doxorubicin in normal tissue after pressurized intraperitoneal aerosol chemotherapy (PIPAC) in a post-mortem swine model. Anticancer Res 37:1677–1680CrossRefPubMedGoogle Scholar
  30. 30.
    Sugarbaker PH, Kern K, Lack E (1987) Malignant pseudomyxoma peritonei of colonic origin. Natural history and presentation of a curative approach to treatment. Dis Colon Rectum 30:772–779CrossRefPubMedGoogle Scholar
  31. 31.
    Piso P, Glockzin G, von Breitenbuch P et al (2009) Patient selection for a curative approach to carcinomatosis. Cancer J 15:236–242CrossRefPubMedGoogle Scholar
  32. 32.
    Sugarbaker PH, Ryan DP (2012) Cytoreductive surgery plus hyperthermic perioperative chemotherapy to treat peritoneal metastases from colorectal cancer: standard of care or an experimental approach? Lancet Oncol 13:e362–e369CrossRefPubMedGoogle Scholar
  33. 33.
    Ceelen WP, Levine E (2015) Intraperitoneal cancer therapy: principles and practice. CRC Press, Boca RatonCrossRefGoogle Scholar
  34. 34.
    Tempfer CB, Celik I, Solass W et al (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 132:307–311CrossRefPubMedGoogle Scholar
  35. 35.
    Ozols RF, Young RC, Speyer JL et al (1982) Phase I and pharmacological studies of adriamycin administered intraperitoneally to patients with ovarian cancer. Cancer Res 42:4265–4269PubMedGoogle Scholar
  36. 36.
    Gianola FJ, Sugarbaker PH, Barofsky I, White DE, Meyers CE (1986) Toxicity studies of adjuvant intravenous versus intraperitoneal 5-FU in patients with advanced primary colon or rectal cancer. Am J Clin Oncol 9:403–410CrossRefPubMedGoogle Scholar
  37. 37.
    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 20:2311–2316CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Reymond MA, Solass W (2014) Pressurized intraperitoneal aerosol chemotherapy (PIPAC)—cancer under pressure. De Gruyter, BerlinGoogle Scholar
  39. 39.
  40. 40.
    Mobus V, Wandt H, Frickhofen N et al (2007) Phase III trial of high-dose sequential chemotherapy with peripheral blood stem cell support compared with standard dose chemotherapy for first-line treatment of advanced ovarian cancer: intergroup trial of the AGO-Ovar/AIO and EBMT. J Clin Oncol 25:4187–4193CrossRefPubMedGoogle Scholar
  41. 41.
    Harter P, Mahner S, Hilpert F et al (2013) Statement by the kommission OVAR of the AGO study group on the use of HIPEC (hyperthermic intraperitoneal chemotherapy) to treat primary and recurrent ovarian cancer. Geburtshilfe Frauenheilkd 73:221–223CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Hahn GM (1979) Potential for therapy of drugs and hyperthermia. Cancer Res 39:2264–2268PubMedGoogle Scholar
  43. 43.
    Meyn RE, Corry PM, Fletcher SE, Demetriades M (1980) Thermal enhancement of DNA damage in mammalian cells treated with cis-diamminedichloroplatinum(II). Cancer Res 40:1136–1139PubMedGoogle Scholar
  44. 44.
    Alberts DS, Peng YM, Chen HS, Moon TE, Cetas TC, Hoeschele JD (1980) Therapeutic synergism of hyperthermia-cis-platinum in a mouse tumor model. J Natl Cancer Inst 65:455–461PubMedGoogle Scholar
  45. 45.
    Los G, van Vugt MJ, Pinedo HM (1994) Response of peritoneal solid tumours after intraperitoneal chemohyperthermia treatment with cisplatin or carboplatin. Br J Cancer 69:235–241CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Akaboshi M, Tanaka Y, Kawai K, Akuta K, Masunaga S, Ono K (1994) Effect of hyperthermia on the number of platinum atoms binding to DNA of HeLa cells treated with 195mPt-radiolabelled cis-diaminedichloroplatinum(II). Int J Radiat Biol 66:215–220CrossRefPubMedGoogle Scholar
  47. 47.
    Herman TS, Teicher BA, Cathcart KN, Kaufmann ME, Lee JB, Lee MH (1988) Effect of hyperthermia on cis-diamminedichloroplatinum(II) (rhodamine 123)2[tetrachloroplatinum(II)] in a human squamous cell carcinoma line and a cis-diamminedichloroplatinum(II)-resistant subline. Cancer Res 48:5101–5105PubMedGoogle Scholar
  48. 48.
    van de Vaart PJ, van der Vange N, Zoetmulder FA et al (1998) Intraperitoneal cisplatin with regional hyperthermia in advanced ovarian cancer: pharmacokinetics and cisplatin-DNA adduct formation in patients and ovarian cancer cell lines. Eur J Cancer 34:148–154CrossRefPubMedGoogle Scholar
  49. 49.
    do Jung H, Son SY, Oo AM et al (2016) Feasibility of hyperthermic pressurized intraperitoneal aerosol chemotherapy in a porcine model. Surg Endosc 30:4258–4264CrossRefGoogle Scholar
  50. 50.
    Kakchekeeva T, Demtroder C, Herath NI et al (2016) In vivo feasibility of electrostatic precipitation as an adjunct to pressurized intraperitoneal aerosol chemotherapy (ePIPAC). Ann Surg Oncol 23:592–598CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Heiss MM, Murawa P, Koralewski P et al (2010) The trifunctional antibody catumaxomab for the treatment of malignant ascites due to epithelial cancer: results of a prospective randomized phase II/III trial. Int J Cancer 127:2209–2221CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Odendahl K, Solass W, Demtroder C et al (2015) Quality of life of patients with end-stage peritoneal metastasis treated with pressurized intraperitoneal aerosol chemotherapy (PIPAC). Eur J Surg Oncol 41:1379–1385CrossRefPubMedGoogle Scholar
  53. 53.
    Teixeira Farinha H, Grass F, Kefleyesus A et al (2017) Impact of pressurized intraperitoneal aerosol chemotherapy on quality of life and symptoms in patients with peritoneal carcinomatosis: a retrospective cohort study. Gastroenterol Res Pract 2017:4596176CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Girshally R, Demtroder C, Albayrak N, Zieren J, Tempfer C, Reymond MA (2016) Pressurized intraperitoneal aerosol chemotherapy (PIPAC) as a neoadjuvant therapy before cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. World J Surg Oncol 14:253CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Tempfer CB, Rezniczek GA, Ende P, Solass W, Reymond MA (2015) Pressurized Intraperitoneal aerosol chemotherapy with cisplatin and doxorubicin in women with peritoneal carcinomatosis: a cohort study. Anticancer Res 35:6723–6729PubMedGoogle Scholar
  56. 56.
    Tempfer CB, Winnekendonk G, Solass W et al (2015) Pressurized intraperitoneal aerosol chemotherapy in women with recurrent ovarian cancer: a phase 2 study. Gynecol Oncol 137:223–228CrossRefPubMedGoogle Scholar
  57. 57.
    Robella M, Vaira M, De Simone M (2016) Safety and feasibility of pressurized intraperitoneal aerosol chemotherapy (PIPAC) associated with systemic chemotherapy: an innovative approach to treat peritoneal carcinomatosis. World J Surg Oncol 14:128CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Rezniczek GA, Jungst F, Jutte H et al (2016) Dynamic changes of tumor gene expression during repeated pressurized intraperitoneal aerosol chemotherapy (PIPAC) in women with peritoneal cancer. BMC Cancer 16:654CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Trimbos JB, Parmar M, Vergote I et al (2003) International Collaborative Ovarian Neoplasm trial 1 and Adjuvant ChemoTherapy In Ovarian Neoplasm trial: two parallel randomized phase III trials of adjuvant chemotherapy in patients with early-stage ovarian carcinoma. J Natl Cancer Inst 95:105–112CrossRefPubMedGoogle Scholar
  60. 60.
    Harter P, Hahmann M, Lueck HJ et al (2009) Surgery for recurrent ovarian cancer: role of peritoneal carcinomatosis: exploratory analysis of the DESKTOP I Trial about risk factors, surgical implications, and prognostic value of peritoneal carcinomatosis. Ann Surg Oncol 16:1324–1330CrossRefPubMedGoogle Scholar
  61. 61.
    Grass F, Vuagniaux A, Teixeira-Farinha H, Lehmann K, Demartines N, Hubner M (2017) Systematic review of pressurized intraperitoneal aerosol chemotherapy for the treatment of advanced peritoneal carcinomatosis. Br J Surg 104:669–678CrossRefPubMedGoogle Scholar
  62. 62.
    Giger-Pabst U, Solass W, Buerkle B et al (2015) Low-dose pressurized intraperitoneal aerosol chemotherapy (PIPAC) as an alternative therapy for ovarian cancer in an octogenarian patient. Anticancer Res 35:2309–2314PubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • A. M. Dueckelmann
    • 1
    Email author
  • D. Fink
    • 2
  • P. Harter
    • 3
  • V. Heinzelmann
    • 4
  • C. Marth
    • 5
  • M. Mueller
    • 6
  • A. Reinthaller
    • 7
  • K. Tamussino
    • 8
  • P. Wimberger
    • 9
  • J. Sehouli
    • 1
  1. 1.Charité Universitätsmedizin BerlinBerlinGermany
  2. 2.University Hospital of ZurichZürichSwitzerland
  3. 3.Kliniken Essen-MitteEssenGermany
  4. 4.University Hospital BaselBaselSwitzerland
  5. 5.Medical University InnsbruckInnsbruckAustria
  6. 6.University Hospiatl BernBernSwitzerland
  7. 7.Medical University of ViennaViennaAustria
  8. 8.Medical University of GrazGrazAustria
  9. 9.University Hospital DresdenDresdenGermany

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