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–Tukey double arcsine transformation, and 95% CIs were calculated using Clopper–Pearson 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 3–4 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 0.61–0.73), 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.

Background: Cytoreductive surgery (CRS) is a technically demanding procedure, and there is considerable debate about its safe application. This study investigated the learning curve for CRS and the clinical outcomes of consecutive patients treated by a single surgeon at a single institution.Methods: We collected 251 consecutive patients who underwent CRS for peritoneal metastases by a single surgeon at Fondazione Policlinico Universitario A. Gemelli IRCCS, between January 2016 and December 2020. The learning curve was estimated using the cumulative summation analysis (CUSUM) for operative time (OT). Risk-adjusted CUSUM (RA-CUSUM) charts were developed using a composite variable (surgical failure), defined as the occurrence of at least one of the following events: major postoperative complications (Clavien–Dindo grade ≥3), blood loss ≥500 mL, incomplete cytoreduction. Three learning phases were thus derived from the RA-CUSUM analysis, and were compared in terms of perioperative outcomes.Results: CUSUM-OT showed that the operation time improved significantly after the 161^th case. RA-CUSUM analysis allowed to break the CRS learning curve into three different phases: phase 1, “the learning phase” (cases 1–99), phase 2 “the experienced phase” (cases 100–188), and phase 3, “the mastership phase” (cases 189–251). The rate of major postoperative complications decreased significantly over the three phases (p = 0.019). Operative time decreased significantly as well (p = 0.031) and was significantly shorter in phase 3 with respect to the other two phases (phase 3 vs phase 2: 420 min vs 500 min, p = 0.017; phase 3 vs phase 1: 420 min vs 503 min, p = 0.021). Blood loss consistently decreased throughout the three phases (p = 0.001). The rate of incomplete cytoreduction was significantly lower in phase 3 than in phase 2 (4.8% vs 14.6%, p = 0.043).Conclusion: The CRS failure rate stabilized after the first 99 cases, and the complete surgical proficiency was achieved after 189 cases. A standardised and mentored learning model is a safer strategy to shorten the learning process, to reduce morbidity and mortality, to improve oncologic outcomes.