{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T18:13:18Z","timestamp":1787508798739,"version":"build-2736575974"},"reference-count":57,"publisher":"BMJ","issue":"8","license":[{"start":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T00:00:00Z","timestamp":1659312000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2022,6,23]]},"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Up to one-fifth of patients with colorectal cancer will develop peritoneal metastases, frequently without other districts\u2019 involvement. Despite the recent unsuccesses of hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal cancer peritoneal metastases treatment, the rationale in the prophylactic setting remains strong. Several clinical and pharmacokinetic data suggest that the efficacy of intraperitoneal chemotherapy is highest when the disease is microscopic. However, robust evidence demonstrating whether the addition of HIPEC for high-risk colorectal cancers offers better control of local recurrence is lacking.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>This is a multicentre randomised phase 3 trial comparing prophylactic surgery plus HIPEC CO2 with mitomycin, over standard surgical excision in patients with colorectal cancer at high risk of peritoneal carcinomatosis; 388 patients will be included in this study. The primary objective is to compare the efficacy of prophylactic surgery (radical colorectal resection, omentectomy, appendectomy, round ligament of the liver resection and bilateral adnexectomy) plus HIPEC CO2 with mitomycin and standard surgery in terms of local recurrence-free survival. The main secondary endpoints are disease-free survival (DFS), overall survival (OS) and safety. The primary endpoint will be described with a cumulative incidence function and will be analysed with Grey test to take account of the competing risks. DFS and OS will be described with the Kaplan-Meier method.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>This trial has been evaluated by the Italian Medicines Agency, local ethics committees and will be submitted to the Ministry of Health to notify the start of the trial according to the regulation of trials on devices with CE mark\/certification.<\/jats:p>\n                    <jats:p>The results will be submitted for presentation at academic meetings and for publication in a peer-reviewed journal, whatever the findings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT03914820\">NCT03914820<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2021-051324","type":"journal-article","created":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T12:17:29Z","timestamp":1659356249000},"page":"e051324","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":6,"title":["Prophylactic surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC CO2) versus standard surgery in colorectal carcinoma at high risk of peritoneal carcinomatosis: short-term and long-term outcomes from the CHECK study \u2013 protocol for a randomised, multicentre, phase 3 trial"],"prefix":"10.1136","volume":"12","clinical-trial-number":[{"clinical-trial-number":"nct03914820","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03914820","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03914820","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Fabio","family":"Pacelli","sequence":"first","affiliation":[{"name":"Chirurgia del Peritoneo e del Retroperitoneo, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Gerardi","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliana","family":"Rulli","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Abatini","sequence":"additional","affiliation":[{"name":"Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3981-0794","authenticated-orcid":false,"given":"Stefano","family":"Rotolo","sequence":"additional","affiliation":[{"name":"Chirurgia del Peritoneo e del Retroperitoneo, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy"},{"name":"Dipartimento di Discipline Chirurgiche, Oncologiche e Stomatologiche (Di.Chir.On.S.), Universit\u00e0 degli Studi di Palermo, Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvio","family":"Garattini","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluigi","family":"Melotti","sequence":"additional","affiliation":[{"name":"Associazione Chirurghi Ospedalieri Italiani, Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valter","family":"Torri","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Galli","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Rulli","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Di Giorgio","sequence":"additional","affiliation":[{"name":"Chirurgia del Peritoneo e del Retroperitoneo, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2022,8,1]]},"reference":[{"key":"2025101811202817000_12.8.e051324.1","unstructured":"AIRTUM . 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