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Objectives: Safe implementation and thorough evaluation of new treatments require prospective data monitoring and standardization of treatments. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a promising alternative for the treatment of patients with peritoneal disease with an increasing number of suggested drug regimens. The aim was to reach expert consensus on current PIPAC treatment protocols and to define the most important research topics., Methods: The expert panel included the most active PIPAC centers, organizers of PIPAC courses and principal investigators of prospective studies on PIPAC. A comprehensive literature review served as base for a two-day hybrid consensus meeting which was accompanied by a modified three-round Delphi process. Consensus bar was set at 70% for combined (strong and weak) positive or negative votes according to GRADE. Research questions were prioritized from 0 to 10 (highest importance)., Results: Twenty-two out of 26 invited experts completed the entire consensus process. Consensus was reached for 10/10 final questions. The combination of doxorubicin (2.1 mg/m 2 ) and cisplatin (10.5 mg/m 2 ) was endorsed by 20/22 experts (90.9%). 16/22 (72.7%) supported oxaliplatin at 120 with potential reduction to 90 mg/m 2 (frail patients), and 77.2% suggested PIPAC-Ox in combination with 5-FU. Mitomycin-C and Nab-paclitaxel were favoured as alternative regimens. The most important research questions concerned PIPAC conditions (n=3), standard (n=4) and alternative regimens (n=5) and efficacy of PIPAC treatment (n=2); 8/14 were given a priority of ≥8/10., Conclusions: The current consensus should help to limit heterogeneity of treatment protocols but underlines the utmost importance of further research., Competing Interests: Competing interests: The following disclosure were made: MH: 1. Research funding (institution): Nestlé health science. 2. Speaker honorary (institution): MSD, Nestlé, Fresenius, Capnomed, Encare. 3. Boards: ERAS society: chair education, ISSPP: chair education. MR: 1.Research funding: Capnomed GmbH, Fisher Paykel, Alesi Surgical. 2. Speaker honorary: Boerhinger Ingelheim. 3. Stock shareholder: Capnomed GmbH. MP: Research funding: Capnomed GmbH, IDmed, INSERM laboratory unit. XD: Speaker honorary: Capnomed GmbH, Consultant for Latin America. WPY: Speaker honorary: Astra Zeneca, BMS, Eli Lilly, Novartis. The rest of the authors have no competing interests., (© 2022 Olivia Sgarbura et al., published by De Gruyter, Berlin/Boston.)

Objectives: To assess the risk perception and the uptake of measures preventing environment-related risks in the operating room (OR) during hyperthermic intraperitoneal chemotherapy (HIPEC) and pressurized intraperitoneal aerosol chemotherapy (PIPAC)., Methods: A multicentric, international survey among OR teams in high-volume HIPEC and PIPAC centers: Surgeons (Surg), Scrub nurses (ScrubN), Anesthesiologists (Anest), Anesthesiology nurses (AnesthN), and OR Cleaning staff (CleanS). Scores extended from 0-10 (maximum)., Results: Ten centers in six countries participated in the study (response rate 100%). Two hundred and eleven responses from 68 Surg (32%), 49 ScrubN (23%), 45 Anest (21%), 31 AnesthN (15%), and 18 CleanS (9%) were gathered. Individual uptake of protection measures was 51.4%, similar among professions and between HIPEC and PIPAC. Perceived levels of protection were 7.57 vs. 7.17 for PIPAC and HIPEC, respectively (p<0.05), with Anesth scoring the lowest (6.81). Perceived contamination risk was 4.19 for HIPEC vs. 3.5 for PIPAC (p<0.01). Information level was lower for CleanS and Anesth for HIPEC and PIPAC procedures compared to all other responders (6.48 vs. 4.86, and 6.48 vs. 5.67, p<0.01). Willingness to obtain more information was 86%, the highest among CleanS (94%)., Conclusions: Experience with the current practice of safety protocols was similar during HIPEC and PIPAC. The individual uptake of protection measures was rather low. The safety perception was better for PIPAC, but the perceived level of protection remained relatively low. The willingness to obtain more information was high. Intensified, standardized training of all OR team members involved in HIPEC and PIPAC is meaningful., Competing Interests: Competing interests: Authors state no conflict of interest., (© 2020 Daniel Clerc et al., published by De Gruyter, Berlin/Boston.)

Objectives: Malignant pleural effusion (MPE) is a devastating evolution of several malignancies. Pressurized intrathoracic aerosol chemotherapy (PITAC) might be a novel therapy option in MPE., Methods: PITAC is considered for patients with MPE with a performance status <2 and without other metastatic sites. General anesthesia is administered and a double-lumen bronchial tube is inserted. The patient is placed in a lateral decubitus position, and the operation is performed after ipsilateral lung exclusion. Two 12-mm balloon trocars are inserted-one in the seventh intercostal space in the mid-axillary line and one in the fifth intercostal space in the anterior axillary line. Extent of pleural disease and volume of MPE are documented. MPE is removed and parietal pleural biopsy are performed. An intrathoracic pressure of 12 mmHg CO 2 is established, and a combination of Cisplatin (10.5 mg/m 2 in a total volume of 150 cc NaCl 0.9%) and Doxorubicin (2.1 mg/m 2 in a total volume of 50 cc NaCl 0.9%) are aerosolized via nebulizer in the pleural cavity. Vital signs and nebulization are remote-controlled. After 30 min, the remaining toxic aerosol is exhausted using a closed surgical smoke evacuation system. A 24Fr chest tube is inserted in postero-apical position with continuous negative pressure of 20 cm H 2 O. When needed, PITAC may be repeated every six weeks in alternate with systemic chemotherapy., Results: In our hands, the technique above has shown to be feasible and safe., Conclusions: Further studies are needed to assess the potential symptomatic and oncological benefits of PITAC in MPE., Competing Interests: Competing interests: Authors state no conflict of interest., (© 2020 Gabrielle Drevet et al., published by De Gruyter, Berlin/Boston.)

Background: Malignant peritoneal mesothelioma (MPM) is a rare tumoral disease characterized by the diffuse involvement of the peritoneal serosa. The standard frontline treatment of MPM is cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) unless the peritoneal disease is considered unresectable. For unresectable patients the standard frontline treatment is a combination of cisplatin and pemetrexed but the prognosis remains ominous with only 13 months of overall survival (OS)., Methods: The proposed study is a multicenter randomized non-comparative study evaluating the association of Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) and systemic chemotherapy vs. systemic chemotherapy alone as first-line treatment of MPM. Patients will be randomized with a 2:1 ratio using a minimization technique. Sixty-six patients have to be enrolled. Stratification will be performed according to histology (epithelioid vs. sarcomatoid and biphasic), presence of extraperitoneal disease and center. Primary objective is OS and secondary objectives include progression-free survival (PFS), safety, compliance, feasibility, conversion to resectability, histological response to treatment and quality of life., Conclusions: We expect to show that intensification of the first line treatment with PIPAC for initially unresectable MPM patients increases OS., Trial Registration: Prospective study. Clinicaltrials.gov: NCT03574493 EudraCT: 2019-001515-23., Competing Interests: Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

Background: Recurrent, platin-resistant ovarian cancer (rPROC) has a poor survival. Even with the AURELIA trial, which is the best available treatment today, progression-free survival (PFS) is still only 6.7 months from the start of the second-line chemotherapy. Innovative, effective therapies are urgently needed. Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) is a novel drug delivery system for administering drugs into the abdomen. PIPAC with cisplatin and doxorubicin (PIPAC C/D) may be safely used at an intraperitoneal dose of 10.5 mg/m 2 and 2.1 mg/m 2 , respectively. Systemic toxicity of this therapy is low. In a phase II trial with 53 women, 62 % patients had an objective tumor response. Tumor regression on histology was observed in 76 % patients who underwent all three PIPACs. Randomized phase III studies are now required to evaluate the effect of PIPAC C/D compared to other standard treatments (sequential or simultaneous applications with systemic chemotherapy)., Methods: The present phase III study is a prospective, open, randomized, multicentric pivotal trial. A total of 244 patients will be randomly assigned (1:1) to the control (A) or to the experimental (B) group. Group A: Systemic palliative chemotherapy, physician's best choice (monotherapy consisting of pegylated liposomal doxorubicin or topotecan or gemcitabine or paclitaxel weekly. Bevacizumab can be used in combination with paclitaxel, topotecan, or pegylated liposomal doxorubicin). Group B: Intraperitoneal chemotherapy, 3×PIPAC C/D, performed every 6 weeks. Combination with systemic therapy is not allowed. Treatment is continued until disease progression, death, or patient refusal. In case of progression, no recommendation for further therapy is given by protocol. Patients are allowed to receive PIPAC C/D or systemic chemotherapy after study termination. The primary endpoint is PFS (according to RECIST v1.1) or death from any cause. The co-primary endpoint is the health-related quality of life (HRQoL) measured as the global health status (GHS, QLQ-30 of EORTC). Secondary outcomes comprise overall survival, safety (CTCAE 5.0), and tumor response according to peritoneal regression grading score (PRGS)., Discussion: We expect PIPAC C/D to control peritoneal disease and preserve the QoL on this subset of patients., Trial Registration: The EudraCT number 2018-003664-31., Competing Interests: Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.