Pressurized Intraperitoneal Aerosol Chemotherapy for Colorectal Peritoneal Metastases



The benefit of repetitive PIPAC specifically in CPM patients has yet to be demonstrated in terms of oncological and functional outcomes.


The aim of this study was to evaluate the outcome of patients with non-resectable colorectal peritoneal metastases (CPM) treated with pressurized intraperitoneal aerosol chemotherapy (PIPAC).


We conducted an analysis of a prospective single-center database of all CPM patients who underwent PIPAC with oxaliplatin 92 mg/m2 body surface (PIPAC-Ox). The outcome criteria were adverse events (Common Terminology Criteria for Adverse Events version 4.0), Peritoneal Regression Grading Score (PRGS), and survival.


Overall, 102 patients with a median age of 64 years (33–88) were scheduled for PIPAC-Ox. Access to the abdominal cavity for the first application failed in 22/102 (21.6%) patients. A total of 185 PIPACs were performed, with 26/102 (25.5%), 20/102 (19.6%), 17/102 (16.7%), and 17/102 (16.7%) patients undergoing one, two, three, and four or more PIPACs, respectively. Perioperative overall morbidity/mortality Grade I–V occurred in 14 (7.6%), 29 (15.8%), 6 (3.2%), 1 (0.5%), and 1 (0.5%) patient without significant differences between each cycle. Of 27 patients who underwent three or more PIPACs, 20/102 (19.6%) had major/complete CPM regression (PRGS 1–2). In a multivariate analysis, independent predictive factors for > 12 months’ survival following the first PIPAC-Ox administration were three or more PIPACs (odds ratio [OR] 4.5, 95% confidence interval [CI] 1.35–15.2; p = 0.014) and younger patient age (OR 1.058, 95% CI 1.00–1.12; p = 0.039).


Repetitive PIPAC-Ox for CPM patients, alone or combined with perioperative systemic chemotherapy, is feasible. Our data suggest that three or more consecutive PIPAC-Ox cycles for advanced CPM can improve survival.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4


  1. 1.

    Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global patterns and trends in colorectal cancer incidence and Mortality. Gut. 2017;66: 683–91.

    Article  Google Scholar 

  2. 2.

    Ferlay J, Soerjomataram I, Ervik M, et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC Cancer Base N0. 11. Lyon; International Agency for Research on Cancer (IARC); 2013.

  3. 3.

    Jayne DG, Fook S, Loi C, Seow-Choen F. Peritoneal carcinomatosis from colorectal cancer. Br J Surg. 2002;89(12):1545–50.

    CAS  Article  Google Scholar 

  4. 4.

    Glehen O, Osinsky D, Beaujard AC, Gilly FN. Natural history of peritoneal carcinomatosis from non-gynecologic malignancies. Surg Oncol Clin N Am. 2003; 123:729–39.

    Article  Google Scholar 

  5. 5.

    Sugarbaker PH, Cunliffe WJ, Belliveau J, et al. Rationale for integrating early postoperative intraperitoneal chemotherapy into the surgical treatment of gastrointestinal cancer. Semin Oncol. 1989;16(4) 06:83–97.

  6. 6.

    Minsky BD, Mies C, Rich TA, Recht A, Chaffey JT. Potentially curative surgery of colon cancer: patterns of failure and survival. J Clin Oncol. 1988;6(1):106–18.

    CAS  Article  Google Scholar 

  7. 7.

    Folprecht G, Köhne CH, Lutz MP. Systemic chemotherapy in patients with peritoneal carcinomatosis from colorectal cancer. Cancer Treat Res. 2007; 134:425–40.

    CAS  PubMed  Google Scholar 

  8. 8.

    Franko J, Shi Q, Goldman CD, et al. Treatment of colorectal peritoneal carcinomatosis with systemic chemotherapy: a pooled analysis of north central cancer treatment group phase III trials N9741 and N9841. J Clin Oncol. 2012;30:263–7.

    Article  Google Scholar 

  9. 9.

    Klaver YL, Simkens LH, Lemmens VE, et al. Outcomes of colorectal cancer patients with peritoneal carcinomatosis treated with chemotherapy with and without targeted therapy. Eur J Surg Oncol. 2012;38:617–23.

    CAS  Article  Google Scholar 

  10. 10.

    Franko J, Shi Q, Meyers JP, et al. Analysis, research in cancers of the digestive system G. prognosis of patients with peritoneal metastatic colorectal cancer given systemic therapy: an analysis of individual patient data from prospective randomised trials from the analysis and research in cancers of the digestive system (ARCAD) database. Lancet Oncol. 2016;17: 1709–19.

  11. 11.

    Elias D, Lefevre JH, Chevalier J, et al. Complete cytoreductive surgery plus intraperitoneal chemohyperthermia with oxaliplatin for peritoneal carcinomatosis of colorectal origin. J Clin Oncol. 2009;27:681–85.

    Article  Google Scholar 

  12. 12.

    Graf W, Cashin PH, Ghanipour L, et al. Prognostic Impact of BRAF and KRAS Mutation in Patients with Colorectal and Appendiceal Peritoneal Metastases Scheduled for CRS and HIPEC. Ann Surg Oncol. 2020; 27:293–300.

    Article  Google Scholar 

  13. 13.

    Quenet F, Elias D, Rocra L, et al. A UNICANCER phase III trial of hyperthermic intra-peritoneal chemotherapy (HIPEC) for colorectal peritoneal carcinomatosis (PC): PRODIGE 7. J Clin Oncol. 2018;36(18).

  14. 14.

    Solaß W, Hetzel A, Nadiradze G, Sagynaliev E, Reymond MA. Description of a novel approach for intraperitoneal drug delivery and the related device. Surg Endosc. 2012;26(7):1849–55.

    Article  Google Scholar 

  15. 15.

    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(2):553–9.

    Article  Google Scholar 

  16. 16.

    Demtröder C, Solass W, Zieren J, Strumberg D, Giger-Pabst U, Reymond MA. Pressurized intraperitoneal aerosol chemotherapy with oxaliplatin in colorectal peritoneal metastasis. Colorectal Dis. 2016;18(4):364–71.

    Article  Google Scholar 

  17. 17.

    Giger-Pabst U, Tempfer CB. How to Perform Safe and Technically Optimized Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC): Experience After a Consecutive Series of 1200 Procedures. J Gastrointest Surg. 2018;22(12):2187–93.

    Article  Google Scholar 

  18. 18.

    Dworak O, Keilholz L, Hoffmann A. Pathological features of rectal cancer after preoperative radiochemotherapy. Int J Colorectal Dis. 1997;12(1):19–23.

    CAS  Article  Google Scholar 

  19. 19.

    International Registry of Patients Treated with Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) [PIPACRegis]. identifier: NCT03210298. Available at:

  20. 20.

    Solass W, Sempoux C, Detlefsen S, Carr NJ, Bibeau F. Peritoneal sampling and histological assessment of therapeutic response in peritoneal metastasis: proposal of the Peritoneal Regression Grading Score (PRGS). Pleura Peritoneum. 2016;1(2):99–107.

    Article  Google Scholar 

  21. 21.

    Common Terminology Criteria for Adverse Events (CTCAE). Version 4.0. Published: 28 May 2009 (v4.03: June 14, 2010). US Department of Health and Human Services, National Institutes of Health, National Cancer Institute.

  22. 22.

    Jacquet P, Sugarbaker PH. Clinical research methodologies in diagnosis and staging of patients with peritoneal carcinomatosis. Cancer Treat Res. 1996;82:359–74.

    CAS  Article  Google Scholar 

  23. 23.

    Faron M, Macovei R, Goéré D, Honoré C, Benhaim L, Elias D. Linear Relationship of Peritoneal Cancer Index and Survival in Patients with Peritoneal Metastases from Colorectal Cancer. Ann Surg Oncol. 2016;23(1):114–9.

    Article  Google Scholar 

  24. 24.

    Aaronson NK, Ahmedzai S, Bergman B, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst. 1993;85:365–76.

    CAS  Article  Google Scholar 

  25. 25.

    Alyami M, Gagniere J, Sgarbura O, et al. Multicentric initial experience with the use of the pressurized intraperitoneal aerosol chemotherapy (PIPAC) in the management of unresectable peritoneal carcinomatosis. Eur J Surg Oncol. 2017;43(11):2178–83.

    Article  Google Scholar 

  26. 26.

    Giger-Pabst U, Demtröder C, Falkenstein TA, et al. Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) for the treatment of malignant mesothelioma. BMC Cancer. 2018;18: 442.

    Article  Google Scholar 

  27. 27.

    Alyami M, Hübner M, Grass F, et al. Pressurised intraperitoneal aerosol chemotherapy: rationale, evidence, and potential indications. Lancet Oncol. 2019;20(7):e368–77.

    Article  Google Scholar 

  28. 28.

    Passot G, You B, Boschetti G, et al. Pathological response to neoadjuvant chemotherapy: a new prognosis tool for the curative management of peritoneal colorectal carcinomatosis. Ann Surg Oncol. 2014;21(8):2608–14.

    Article  Google Scholar 

  29. 29.

    Yonemura Y, Canbay E, Haruaki I. Prognostic Factors of Peritoneal Metastases from Colorectal Cancer following Cytoreductive Surgery and Perioperative Chemotherapy. Sci World J. 2013;2013:978394.

    Article  Google Scholar 

  30. 30.

    Robella M, Vaira M, De Simone M. Safety and feasibility of pressurized intraperitoneal aerosol chemotherapy (PIPAC) associated with systemic chemotherapy: an innovative approach to treat peritoneal carcinomatosis. World J Surg Oncol. 2016;14:128.

    Article  Google Scholar 

  31. 31.

    Solass W, Sempoux C, Carr NJ, et al. Reproducibility of the peritoneal regression grading score for assessment of response to therapy in peritoneal metastasis. Histopathology. 2019;74(7):1014–24.

    Article  Google Scholar 

  32. 32.

    Chetty R, Gill P, Govender D, et al. International study group on rectal cancer regression grading: interobserver variability with commonly used regression grading systems. Hum Pathol. 2012;43:1917–23.

    Article  Google Scholar 

  33. 33.

    Vironen J, Juhola M, Kairaluoma M, et al. Tumour regression grading in the evaluation of tumour response after different preoperative radiotherapy treatments for rectal carcinoma. Int J Colorectal Dis. 2005;20:440–4.

    CAS  Article  Google Scholar 

  34. 34.

    Graversen M, Detlefsen S, Pfeiffer P, et al. Severe peritoneal sclerosis after repeated pressurized intraperitoneal aerosol chemotherapy with oxaliplatin (PIPAC OX): report of two cases and literature survey. Clin Exp Metastasis. 2018;35(3):103–8.

    CAS  Article  Google Scholar 

  35. 35.

    Ploug M, Graversen M, Pfeiffer P, et al. Bidirectional treatment of peritoneal metastasis with Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) and systemic chemotherapy: a systematic review. BMC Cancer. 2020;20:105.

    Article  Google Scholar 

Download references

Author information




NT, JB, CRD, JT, GR, CBT, BF, CD, TL, MO and UGP made substantial contributions to the study conception and design, acquisition of data, and/or analysis and interpretation of data; participated in drafting or critically revising the manuscript for important intellectual content; and gave approval for the final version to be published.

Corresponding author

Correspondence to Mehdi Ouaissi MD, PhD.

Ethics declarations


The authors received no specific funding for this work. Nicolas Tabchouri, Jonathan Buggisch, Cédric Rémy Demtröder, Julien Thierry, Günther Rezniczek, Clemens B. Tempfer, Britta Fischer, Can Dogan, Mehdi Ouaissi, and Urs Giger-Pabst have no conflict of interest. Thierry Lecomte receives personal fees from Amgen, Merk Serono, Servier, Sanofi Genzyme and non-financial support from Amgen and Servier.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Tabchouri, N., Buggisch, J., Demtröder, C.R. et al. Pressurized Intraperitoneal Aerosol Chemotherapy for Colorectal Peritoneal Metastases. Ann Surg Oncol (2021).

Download citation