{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T23:04:43Z","timestamp":1785539083942,"version":"3.56.0"},"reference-count":45,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,2,24]],"date-time":"2022-02-24T00:00:00Z","timestamp":1645660800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB 685"],"award-info":[{"award-number":["SFB 685"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["EXC 2180 \u2013 390900677"],"award-info":[{"award-number":["EXC 2180 \u2013 390900677"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002345","name":"University of T\u00fcbingen","doi-asserted-by":"publisher","award":["Open Access Publishing Fund"],"award-info":[{"award-number":["Open Access Publishing Fund"]}],"id":[{"id":"10.13039\/501100002345","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001646","name":"Robert Bosch Stiftung","doi-asserted-by":"publisher","award":["\/"],"award-info":[{"award-number":["\/"]}],"id":[{"id":"10.13039\/501100001646","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) was considered a promising treatment for patients with peritoneal metastasis from colorectal cancer. However, the recently published randomized controlled PRODIGE 7 trial failed to demonstrate survival benefits through the addition of short-term oxaliplatin-based HIPEC. Constituting a complex multifactorial treatment, we investigated HIPEC in a preclinical model concerning the elimination of minimal tumor residues, thereby aiming to better understand the size of effects and respective clinical trial results. Patient samples of peritoneal perfusates obtained during HIPEC treatments and oxaliplatin-containing solutions at clinically relevant dosages, conforming with established HIPEC protocols, were assessed regarding their ability to eliminate modelled ~100 \u00b5m thickness cancer cell layers. Impedance-based real-time cell analysis and classical end-point assays were used. Flow cytometry was employed to determine the effect of different HIPEC drug solvents on tumor cell properties. Effectiveness of peritoneal perfusate patient samples and defined oxaliplatin-containing solutions proved limited but reproducible. HIPEC simulations for 30 min reduced the normalized cell index below 50% with peritoneal perfusates from merely 3 out of 9 patients within 72 h, indicating full-thickness cytotoxic effects. Instead, prolonging HIPEC to 1 h enhanced these effects and comprised 7 patients\u2019 samples, while continuous drug exposure invariably resulted in complete cell death. Further, frequently used drug diluents caused approximately 25% cell size reduction within 30 min. Prolonging oxaliplatin exposure improved effectiveness of HIPEC to eliminate micrometastases in our preclinical model. Accordingly, insufficient penetration depth, short exposure time, and the physicochemical impact of drug solvents may constitute critical factors.<\/jats:p>","DOI":"10.3390\/cancers14051158","type":"journal-article","created":{"date-parts":[[2022,2,24]],"date-time":"2022-02-24T07:22:35Z","timestamp":1645687355000},"page":"1158","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Prolonged Exposure to Oxaliplatin during HIPEC Improves Effectiveness in a Preclinical Micrometastasis Model"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3625-784X","authenticated-orcid":false,"given":"Nick","family":"Seyfried","sequence":"first","affiliation":[{"name":"Department of General, Visceral and Transplant Surgery, University Hospital T\u00fcbingen, Hoppe-Seyler-Str. 3, 72076 T\u00fcbingen, Germany"},{"name":"Interfaculty Institute for Cell Biology, Department of Immunology, University of T\u00fcbingen, Auf der Morgenstelle 15, 72076 T\u00fcbingen, Germany"},{"name":"Department of Surgery, Klinikum Rechts der Isar, Technical University of Munich (TUM), Ismaninger Str. 22, 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9720-8243","authenticated-orcid":false,"given":"Can","family":"Yurttas","sequence":"additional","affiliation":[{"name":"Department of General, Visceral and Transplant Surgery, University Hospital T\u00fcbingen, Hoppe-Seyler-Str. 3, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Burkard","sequence":"additional","affiliation":[{"name":"Institute of Nutritional Sciences, Department of Nutritional Biochemistry, University of Hohenheim, Garbenstr. 30, 70599 Stuttgart, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedikt","family":"Oswald","sequence":"additional","affiliation":[{"name":"Interfaculty Institute for Cell Biology, Department of Immunology, University of T\u00fcbingen, Auf der Morgenstelle 15, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9163-7127","authenticated-orcid":false,"given":"Alexander","family":"Tolios","sequence":"additional","affiliation":[{"name":"Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, W\u00e4hringer G\u00fcrtel 18-20, 1090 Vienna, Austria"},{"name":"Center for Physiology and Pharmacology, Institute of Vascular Biology and Thrombosis Research, Medical University of Vienna, Schwarzspanierstra\u00dfe 17A, 1090 Vienna, Austria"},{"name":"Center for Medical Statistics, Informatics and Intelligent Systems, Institute of Artificial Intelligence, Medical University of Vienna, Spitalgasse 23, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska","family":"Herster","sequence":"additional","affiliation":[{"name":"Interfaculty Institute for Cell Biology, Department of Immunology, University of T\u00fcbingen, Auf der Morgenstelle 15, 72076 T\u00fcbingen, Germany"},{"name":"Robert Bosch Center for Tumor Diseases (RBCT), Robert Bosch Hospital, Auerbachstr. 110, 70376 Stuttgart, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1632-0167","authenticated-orcid":false,"given":"Joseph","family":"Kauer","sequence":"additional","affiliation":[{"name":"Interfaculty Institute for Cell Biology, Department of Immunology, University of T\u00fcbingen, Auf der Morgenstelle 15, 72076 T\u00fcbingen, Germany"},{"name":"German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) Partner Site T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital T\u00fcbingen, Otfried-M\u00fcller-Str. 10, 72076 T\u00fcbingen, Germany"},{"name":"Department of Hematology, Oncology, and Rheumatology, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2390-0226","authenticated-orcid":false,"given":"Tarkan","family":"J\u00e4ger","sequence":"additional","affiliation":[{"name":"Department of Surgery, Paracelsus Medical University, M\u00fcllner Hauptstra\u00dfe 48, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingmar","family":"K\u00f6nigsrainer","sequence":"additional","affiliation":[{"name":"Department of General, Visceral and Transplant Surgery, University Hospital T\u00fcbingen, Hoppe-Seyler-Str. 3, 72076 T\u00fcbingen, Germany"},{"name":"Department of General, Visceral and Thoracic Surgery, Landeskrankenhaus Feldkirch, Carinagasse 47, 6800 Feldkirch, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolin","family":"Thiel","sequence":"additional","affiliation":[{"name":"Department of General, Visceral and Transplant Surgery, University Hospital T\u00fcbingen, Hoppe-Seyler-Str. 3, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2206-107X","authenticated-orcid":false,"given":"Markus","family":"Quante","sequence":"additional","affiliation":[{"name":"Department of General, Visceral and Transplant Surgery, University Hospital T\u00fcbingen, Hoppe-Seyler-Str. 3, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1614-2647","authenticated-orcid":false,"given":"Hans-Georg","family":"Rammensee","sequence":"additional","affiliation":[{"name":"Interfaculty Institute for Cell Biology, Department of Immunology, University of T\u00fcbingen, Auf der Morgenstelle 15, 72076 T\u00fcbingen, Germany"},{"name":"German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) Partner Site T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"Cluster of Excellence iFIT (EXC2180) \u2018Image-Guided and Functionally Instructed Tumor Therapies\u2019, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sascha","family":"Venturelli","sequence":"additional","affiliation":[{"name":"Institute of Nutritional Sciences, Department of Nutritional Biochemistry, University of Hohenheim, Garbenstr. 30, 70599 Stuttgart, Germany"},{"name":"Department of Vegetative and Clinical Physiology, Institute of Physiology, University of T\u00fcbingen, Wilhelmstr. 56, 72074 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Schwab","sequence":"additional","affiliation":[{"name":"German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) Partner Site T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"Cluster of Excellence iFIT (EXC2180) \u2018Image-Guided and Functionally Instructed Tumor Therapies\u2019, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"Department of Clinical Pharmacology, University Hospital T\u00fcbingen, Auf der Morgenstelle 8, 72076 T\u00fcbingen, Germany"},{"name":"Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Auerbachstr. 112, 70376 Stuttgart, Germany"},{"name":"Departments of Pharmacy and Biochemistry, University of T\u00fcbingen, Auf der Morgenstelle 15, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfred","family":"K\u00f6nigsrainer","sequence":"additional","affiliation":[{"name":"Department of General, Visceral and Transplant Surgery, University Hospital T\u00fcbingen, Hoppe-Seyler-Str. 3, 72076 T\u00fcbingen, Germany"},{"name":"German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) Partner Site T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"Cluster of Excellence iFIT (EXC2180) \u2018Image-Guided and Functionally Instructed Tumor Therapies\u2019, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Beckert","sequence":"additional","affiliation":[{"name":"Department of General, Visceral and Transplant Surgery, University Hospital T\u00fcbingen, Hoppe-Seyler-Str. 3, 72076 T\u00fcbingen, Germany"},{"name":"Department of General and Visceral Surgery, Schwarzwald-Baar Hospital, Klinikstr. 11, 78052 Villingen-Schwenningen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2513-1317","authenticated-orcid":false,"given":"Markus W.","family":"L\u00f6ffler","sequence":"additional","affiliation":[{"name":"Department of General, Visceral and Transplant Surgery, University Hospital T\u00fcbingen, Hoppe-Seyler-Str. 3, 72076 T\u00fcbingen, Germany"},{"name":"Interfaculty Institute for Cell Biology, Department of Immunology, University of T\u00fcbingen, Auf der Morgenstelle 15, 72076 T\u00fcbingen, Germany"},{"name":"German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) Partner Site T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"Cluster of Excellence iFIT (EXC2180) \u2018Image-Guided and Functionally Instructed Tumor Therapies\u2019, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"Department of Clinical Pharmacology, University Hospital T\u00fcbingen, Auf der Morgenstelle 8, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3737","DOI":"10.1200\/JCO.2003.04.187","article-title":"Randomized Trial of Cytoreduction and Hyperthermic 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