{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T00:44:22Z","timestamp":1790988262497,"version":"4.1.0"},"reference-count":74,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T00:00:00Z","timestamp":1675900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"AIRC","award":["24285"],"award-info":[{"award-number":["24285"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel intraperitoneal drug delivery method of low-dose chemotherapy as a pressurized aerosol in patients affected by peritoneal cancer of primary or secondary origin. We performed a systematic review and meta-analysis with the aim of assessing the feasibility, safety, and efficacy of PIPAC. Methods: A systematic literature search was performed using Medline and Web of Science databases from 1 January 2011, to inception, to 31 December 2021. Data were independently extracted by two authors. The Newcastle-Ottawa Scale was used to assess the quality and risk of bias of studies. Meta-analysis was performed for pathological response, radiological response, PCI variation along treatment, and for patients undergoing three or more PIPAC. Pooled analyses were performed using the Freeman\u2013Tukey double arcsine transformation, and 95% CIs were calculated using Clopper\u2013Pearson exact CIs in all instances. Results: A total of 414 papers on PIPAC were identified, and 53 studies considering 4719 PIPAC procedure in 1990 patients were included for analysis. The non-access rate or inability to perform PIPAC pooled rate was 4% of the procedures performed. The overall proportion of patients who completed 3 or more cycles of PIPAC was 39%. Severe toxicities considering CTCAE 3\u20134 were 4% (0% to 38.5%). In total, 50 studies evaluated deaths within the first 30 postoperative days. In the included 1936 patients were registered 26 deaths (1.3%). The pooled analysis of all the studies reporting a pathological response was 68% (95% CI 0.61\u20130.73), with an acceptable heterogeneity (I2 28.41%, p = 0.09). In total, 10 papers reported data regarding the radiological response, with high heterogeneity and a weighted means of 15% (0% to 77.8%). PCI variation along PIPAC cycles were reported in 14 studies. PCI diminished, increased, or remained stable in eight, one and five studies, respectively, with high heterogeneity at pooled analysis. Regarding survival, there was high heterogeneity. The 12-month estimated survival from first PIPAC for colorectal cancer, gastric cancer, gynecological cancer and hepatobiliary\/pancreatic cancer were, respectively, 53%, 25%, 59% and 37%. Conclusions: PIPAC may be a useful treatment option for selected patients with PM, with acceptable grade 3 and 4 toxicity and promising survival benefit. Meta-analysis showed high heterogeneity of data among up-to-date available studies. In a subset analysis per primary tumor origin, pathological tumor regression was documented in 68% of the studies with acceptable heterogeneity. Pathological regression seems, therefore, a reliable outcome for PIPAC activity and a potential surrogate endpoint of treatment response. We recommend uniform selection criteria for patients entering a PIPAC program and highlight the urgent need to standardize items for PIPAC reports and datasets.<\/jats:p>","DOI":"10.3390\/cancers15041125","type":"journal-article","created":{"date-parts":[[2023,2,10]],"date-time":"2023-02-10T01:35:29Z","timestamp":1675992929000},"page":"1125","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":91,"title":["10 Years of Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC): A Systematic Review and Meta-Analysis"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3981-1145","authenticated-orcid":false,"given":"Andrea","family":"Di Giorgio","sequence":"first","affiliation":[{"name":"Surgical Unit of Peritoneum and Retroperitoneum, Fondazione Policlinico Universitario A. Gemelli\u2014IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Macr\u00ec","sequence":"additional","affiliation":[{"name":"U.O.C.\u2014P.S.G. con O.B.I. Azienda Ospedaliera Universitaria \u201cG. Martino\u201d\u2014Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8040-2231","authenticated-orcid":false,"given":"Federica","family":"Ferracci","sequence":"additional","affiliation":[{"name":"Surgical Unit of Peritoneum and Retroperitoneum, Fondazione Policlinico Universitario A. Gemelli\u2014IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7676-9658","authenticated-orcid":false,"given":"Manuela","family":"Robella","sequence":"additional","affiliation":[{"name":"Candiolo Cancer Institute, FPO\u2014IRCCS, Candiolo, 10060 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Visaloco","sequence":"additional","affiliation":[{"name":"U.O.C.\u2014P.S.G. con O.B.I. Azienda Ospedaliera Universitaria \u201cG. Martino\u201d\u2014Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"De Manzoni","sequence":"additional","affiliation":[{"name":"Upper GI Surgery Division, University of Verona, 37129 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Sammartino","sequence":"additional","affiliation":[{"name":"CRS and HIPEC Unit, Pietro Valdoni, Umberto I Policlinico di Roma, 00161 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5764-5606","authenticated-orcid":false,"given":"Antonio","family":"Sommariva","sequence":"additional","affiliation":[{"name":"Advanced Surgical Oncology Unit, Surgical Oncology of the Esophagus and Digestive Tract, Veneto Institute of Oncology IOV-IRCCS, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Biacchi","sequence":"additional","affiliation":[{"name":"CRS and HIPEC Unit, Pietro Valdoni, Umberto I Policlinico di Roma, 00161 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4122-1259","authenticated-orcid":false,"given":"Franco","family":"Roviello","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery, and Neurosciences, Unit of General Surgery and Surgical Oncology, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Pastorino","sequence":"additional","affiliation":[{"name":"Sezione di Igiene, Dipartimento Universitario Scienze della Vita e Sanit\u00e0 Pubblica, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Roma, Italy"},{"name":"Department of Woman and Child Health and Public Health\u2014Public Health Area, Fondazione Policlinico Universitario A. Gemelli\u2014IRCCS, 00168 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"Pires Marafon","sequence":"additional","affiliation":[{"name":"Sezione di Igiene, Dipartimento Universitario Scienze della Vita e Sanit\u00e0 Pubblica, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Rotolo","sequence":"additional","affiliation":[{"name":"Department of Surgical, Oncological and Oral Sciences (Di.Chir.On.S.), University of Palermo, 90133 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Casella","sequence":"additional","affiliation":[{"name":"Upper GI Surgery Division, University of Verona, 37129 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Vaira","sequence":"additional","affiliation":[{"name":"Candiolo Cancer Institute, FPO\u2014IRCCS, Candiolo, 10060 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e368","DOI":"10.1016\/S1470-2045(19)30318-3","article-title":"Pressurised Intraperitoneal Aerosol Chemotherapy: Rationale, Evidence, and Potential Indications","volume":"20","author":"Alyami","year":"2019","journal-title":"Lancet Oncol."},{"key":"ref_2","unstructured":"Higgins, J., James, T., Chandler, J., Cumpston, M., Li, T., Page, M.J., and Welch, V.A. 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