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Feasibility and safety of PIPAC combined with additional surgical procedures: PLUS study

      Abstract

      Background

      PIPAC (Pressurized IntraPeritoneal Aerosol Chemotherapy) is a minimally invasive approach relying on physical principles for improving intraperitoneal drug delivery, including optimizing the homogeneity of drug distribution through an aerosol. Feasibility and safety of the new approach are now consolidated and data on its effectiveness are continuously increasing. Although any surgical procedure associated with PIPAC had always been discouraged due to the high risk of complications, surgical practice is constantly changing: with growing expertise, more and more surgical teams associate PIPAC with surgery.

      Methods

      PLUS study is part of the retrospective international cohort studies including 10 centers around the world (India, Italy, France, Germany, Belgium, Russia, Saudi Arabia, Switzerland) and 96 cases of combined approaches evaluated through a propensity score analysis.

      Results

      the procedures most frequently associated with PIPAC were not only adhesiolysis, omentectomy, adnexectomy, umbilical/inguinal hernia repairs, but also more demanding procedures such as intestinal resections, gastrectomy, splenectomy, bowel repair/stoma creation. Although the evidence is currently limited, PLUS study demonstrated that PIPAC associated with additional surgical procedures is linked to an increase of surgical time (p < 0.001), length of stay (p < 0.001) and medical complication rate (p < 0.001); the most frequently reported medical complications were mild or moderate in severity, such as abdominal pain, nausea, ileus and hyperthermia. No difference in terms of surgical complications was registered; neither reoperation or postoperative deaths were reported.

      Conclusions

      these results suggest that PIPAC can be safely combined in expert centers with additional surgeries. Widespread change of practice should be discouraged before the results of ongoing prospective studies are available.

      Keywords

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      References

        • 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 (In eng): 553-559https://doi.org/10.1245/s10434-013-3213-1
        • Solass W.
        • Giger-Pabst U.
        • Zieren J.
        • Reymond M.A.
        Pressurized intraperitoneal aerosol chemotherapy (PIPAC): occupational health and safety aspects.
        Ann Surg Oncol. 2013; 20 (In eng): 3504-3511https://doi.org/10.1245/s10434-013-3039-x
        • Grass F.
        • Vuagniaux A.
        • Teixeira-Farinha H.
        • Lehmann K.
        • Demartines N.
        • Hübner M.
        Systematic review of pressurized intraperitoneal aerosol chemotherapy for the treatment of advanced peritoneal carcinomatosis.
        Br J Surg. 2017; 104 (In eng): 669-678https://doi.org/10.1002/bjs.10521
        • Tempfer C.
        • Giger-Pabst U.
        • Hilal Z.
        • Dogan A.
        • Rezniczek G.A.
        Pressurized intraperitoneal aerosol chemotherapy (PIPAC) for peritoneal carcinomatosis: systematic review of clinical and experimental evidence with special emphasis on ovarian cancer.
        Arch Gynecol Obstet. 2018; 298 (In eng): 243-257https://doi.org/10.1007/s00404-018-4784-7
        • Alyami M.
        • Hübner M.
        • Grass F.
        • et al.
        Pressurised intraperitoneal aerosol chemotherapy: rationale, evidence, and potential indications.
        Lancet Oncol. 2019; 20 (In eng): e368-e377https://doi.org/10.1016/S1470-2045(19)30318-3
        • Hübner M.
        • Grass F.
        • Teixeira-Farinha H.
        • Pache B.
        • Mathevet P.
        • Demartines N.
        Pressurized IntraPeritoneal aerosol chemotherapy - practical aspects.
        Eur J Surg Oncol. 2017; 43 (In eng): 1102-1109https://doi.org/10.1016/j.ejso.2017.03.019
        • Giger-Pabst U.
        • Tempfer C.B.
        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 (In eng): 2187-2193https://doi.org/10.1007/s11605-018-3916-5
        • Vaira M.
        • Robella M.
        • Borsano A.
        • De Simone M.
        Single-port access for pressurized IntraPeritoneal aerosol chemotherapy (PIPAC): technique, feasibility and safety.
        Pleura Peritoneum. 2016; 1 (In eng): 217-222https://doi.org/10.1515/pp-2016-0021
        • 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 (In eng): 128https://doi.org/10.1186/s12957-016-0892-7
        • Tempfer C.B.
        • Winnekendonk G.
        • Solass W.
        • et al.
        Pressurized intraperitoneal aerosol chemotherapy in women with recurrent ovarian cancer: a phase 2 study.
        Gynecol Oncol. 2015; 137 (In eng): 223-228https://doi.org/10.1016/j.ygyno.2015.02.009
        • Demtröder C.
        • Solass W.
        • Zieren J.
        • Strumberg D.
        • Giger-Pabst U.
        • Reymond M.A.
        Pressurized intraperitoneal aerosol chemotherapy with oxaliplatin in colorectal peritoneal metastasis.
        Colorectal Dis. 2016; 18 (In eng): 364-371https://doi.org/10.1111/codi.13130
        • Nadiradze G.
        • Giger-Pabst U.
        • Zieren J.
        • Strumberg D.
        • Solass W.
        • Reymond M.A.
        Pressurized intraperitoneal aerosol chemotherapy (PIPAC) with low-dose cisplatin and doxorubicin in gastric peritoneal metastasis.
        J Gastrointest Surg. 2016; 20 (In eng): 367-373https://doi.org/10.1007/s11605-015-2995-9
        • Struller F.
        • Horvath P.
        • Solass W.
        • et al.
        Pressurized intraperitoneal aerosol chemotherapy with low-dose cisplatin and doxorubicin (PIPAC C/D) in patients with gastric cancer and peritoneal metastasis: a phase II study.
        Ther Adv Med Oncol. 2019; 11 (1758835919846402. (In eng))https://doi.org/10.1177/1758835919846402
        • De Simone M.
        • Vaira M.
        • Argenziano M.
        • et al.
        Pressurized intraperitoneal aerosol chemotherapy (PIPAC) with oxaliplatin, cisplatin, and doxorubicin in patients with peritoneal carcinomatosis: an open-label, single-arm, phase II clinical trial.
        Biomedicines. 2020; 8 (In eng)https://doi.org/10.3390/biomedicines8050102
        • Tavernier C.
        • Passot G.
        • Vassal O.
        • et al.
        Pressurized intraperitoneal aerosol chemotherapy (PIPAC) might increase the risk of anastomotic leakage compared to HIPEC: an experimental study.
        Surg Endosc. 2020; 34 (In eng): 2939-2946https://doi.org/10.1007/s00464-019-07076-3
        • Ellebæk S.B.
        • Graversen M.
        • Detlefsen S.
        • et al.
        Pressurized intraperitoneal aerosol chemotherapy (PIPAC) of peritoneal metastasis from gastric cancer: a descriptive cohort study.
        Clin Exp Metastasis. 2020; 37 (In eng): 325-332https://doi.org/10.1007/s10585-020-10023-5
        • Verwaal V.J.
        • van Tinteren H.
        • Ruth S.V.
        • Zoetmulder F.A.
        Toxicity of cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy.
        J Surg Oncol. 2004; 85 (In eng): 61-67https://doi.org/10.1002/jso.20013
        • Smeenk R.M.
        • Verwaal V.J.
        • Zoetmulder F.A.
        Toxicity and mortality of cytoreduction and intraoperative hyperthermic intraperitoneal chemotherapy in pseudomyxoma peritonei--a report of 103 procedures.
        Eur J Surg Oncol. 2006; 32 (In eng): 186-190https://doi.org/10.1016/j.ejso.2005.08.009
        • Simkens G.A.
        • Verwaal V.J.
        • Lemmens V.E.
        • Rutten H.J.
        • de Hingh I.H.
        Short-term outcome in patients treated with cytoreduction and HIPEC compared to conventional colon cancer surgery.
        Medicine (Baltim). 2016; 95 (In eng)e5111https://doi.org/10.1097/MD.0000000000005111
        • Verwaal V.J.
        • Funder J.A.
        • Sørensen M.M.
        • Iversen L.H.
        The impact of postoperative complications following cytoreductive surgery combined with oxaliplatin based heated intraperitoneal chemotherapy.
        Eur J Surg Oncol. 2021; (In eng)https://doi.org/10.1016/j.ejso.2021.08.027
        • Sgarbura O.
        • Villeneuve L.
        • Alyami M.
        • et al.
        Current practice of pressurized intraperitoneal aerosol chemotherapy (PIPAC): still standardized or on the verge of diversification?.
        Eur J Surg Oncol. 2020; (In eng)https://doi.org/10.1016/j.ejso.2020.08.020
        • Robella M.
        • De Simone M.
        • Berchialla P.
        • et al.
        A phase I dose escalation study of oxaliplatin, cisplatin and doxorubicin applied as PIPAC in patients with peritoneal carcinomatosis.
        Cancers. 2021; 13 (In eng)https://doi.org/10.3390/cancers13051060
        • Tempfer C.B.
        • Giger-Pabst U.
        • Seebacher V.
        • Petersen M.
        • Dogan A.
        • Rezniczek G.A.
        A phase I, single-arm, open-label, dose escalation study of intraperitoneal cisplatin and doxorubicin in patients with recurrent ovarian cancer and peritoneal carcinomatosis.
        Gynecol Oncol. 2018; 150 (In eng): 23-30https://doi.org/10.1016/j.ygyno.2018.05.001
        • Kim G.
        • Tan H.L.
        • Sundar R.
        • et al.
        PIPAC-OX: a phase I study of oxaliplatin-based pressurized intraperitoneal aerosol chemotherapy in patients with peritoneal metastases.
        Clin Cancer Res. 2020; (In eng)https://doi.org/10.1158/1078-0432.CCR-20-2152
        • Dumont F.
        • Senellart H.
        • Pein F.
        • et al.
        Phase I/II study of oxaliplatin dose escalation via a laparoscopic approach using pressurized aerosol intraperitoneal chemotherapy (PIPOX trial) for nonresectable peritoneal metastases of digestive cancers (stomach, small bowel and colorectal): rationale and design.
        Pleura Peritoneum. 2018; 3 (In eng): 20180120https://doi.org/10.1515/pp-2018-0120
        • Van De Sande L.
        • Graversen M.
        • Hubner M.
        • et al.
        Intraperitoneal aerosolization of albumin-stabilized paclitaxel nanoparticles (Abraxane™) for peritoneal carcinomatosis - a phase I first-in-human study.
        Pleura Peritoneum. 2018; 3 (In eng)20180112https://doi.org/10.1515/pp-2018-0112
        • Robella M.
        • Vaira M.
        • Argenziano M.
        • et al.
        Exploring the use of pegylated liposomal doxorubicin (caelyx.
        Front Pharmacol. 2019; 10 (In eng): 669https://doi.org/10.3389/fphar.2019.00669
        • 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 (In eng): 2178-2183https://doi.org/10.1016/j.ejso.2017.09.010
        • Hübner M.
        • Alyami M.
        • Villeneuve L.
        • et al.
        Consensus guidelines for pressurized intraperitoneal aerosol chemotherapy: technical aspects and treatment protocols.
        Eur J Surg Oncol. 2021; (In eng)https://doi.org/10.1016/j.ejso.2021.10.028