{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T12:01:30Z","timestamp":1784808090588,"version":"3.55.0"},"reference-count":27,"publisher":"Walter de Gruyter GmbH","issue":"1","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,8,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Intraperitoneal (IP) chemotherapy (IPC), including hyperthermic intraperitoneal chemotherapy (HIPEC), has emerged as a promising approach to control peritoneal metastases in gastrointestinal (GI) cancers. However, the safety profile and toxicity spectrum of IPC remain incompletely understood. This study aimed to evaluate the incidence of hematologic and biochemical adverse reactions following surgery with or without IPC and to compare the toxicity profiles of normothermic IPC and HIPEC. Additionally, potential risk factors for liver injury were investigated to guide clinical management.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this retrospective cohort study, 449 patients with gastric or colorectal cancer undergoing surgical resection between January 2015 and September 2019 were analyzed. Patients were categorized into three groups: surgery alone (\n                      <jats:italic>n<\/jats:italic>\n                      = 171), surgery + normothermic IPC (IPC group,\n                      <jats:italic>n<\/jats:italic>\n                      = 82), and surgery + HIPEC (HIPEC group,\n                      <jats:italic>n<\/jats:italic>\n                      = 196). Baseline demographic and clinicopathological data, IPC details (including drug regimen, HIPEC technique [open vs closed], and perfusion duration), and postoperative laboratory toxicities were recorded. Hematologic toxicities (leucopenia, neutropenia, thrombocytopenia, and hemoglobin decline) and biochemical toxicities (liver and renal function abnormalities and D-dimer elevation) were graded according to CTCAE v5.0. Group comparisons were performed using\n                      <jats:italic>\u03c7<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      or ANOVA tests. Due to a higher proportion of advanced-stage patients in the HIPEC group, stratified analyses were performed by clinical stage (I\u2013II vs III\u2013IV). Logistic regression was used to identify independent risk factors for liver injury in both IPC and HIPEC groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Baseline characteristics were comparable across groups except for clinical stage, with the HIPEC group having a higher percentage of advanced-stage patients (79.6 vs 59.8%,\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.05). Compared with the surgery-alone group, both IPC and HIPEC groups had significantly higher incidences of hemoglobin decline (25.7% vs 39.0% vs 49.0%, respectively;\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.01), liver injury (37.4% vs 62.2% vs 60.7%,\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.01), and D-dimer elevation (47.4% vs 68.3% vs 72.9%,\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.01). In contrast, the incidences of leucopenia, neutropenia, and renal impairment were low (&lt;12%) and did not differ significantly among groups. Thrombocytopenia was significantly more frequent in the HIPEC group than in the surgery-alone group (7.7 vs 2.9%,\n                      <jats:italic>P<\/jats:italic>\n                      = 0.046). Stratified analyses revealed no significant differences in adverse reaction rates between the IPC and HIPEC groups when adjusted by clinical stage. Multivariate logistic regression indicated that, in the IPC group, severe postoperative GI reactions ( \u2265Grade II; OR, 3.72; 95% CI, 1.20\u201311.55;\n                      <jats:italic>P<\/jats:italic>\n                      = 0.023) and the use of a platinum plus docetaxel regimen (OR, 8.75; 95% CI, 1.78\u201343.12;\n                      <jats:italic>P<\/jats:italic>\n                      = 0.008) were independent predictors of liver injury. In the HIPEC group, the platinum plus docetaxel regimen was also associated with higher liver toxicity, and the open HIPEC technique significantly increased the risk (OR 4.80, 95% CI 1.26\u201318.38,\n                      <jats:italic>P<\/jats:italic>\n                      = 0.020).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Both normothermic IPC and HIPEC significantly increase the risk of certain perioperative laboratory abnormalities \u2013 specifically, anemia, liver injury, and a hypercoagulable state \u2013 compared to surgery alone. Notably, the addition of hyperthermia does not appear to significantly exacerbate the overall toxicity when clinical stage is considered. The chemotherapeutic regimen and HIPEC technique (open vs closed) are key determinants of liver injury. These findings underscore the importance of tailoring IPC protocols and implementing targeted supportive measures, such as liver protection and thromboprophylaxis, to optimize treatment safety in GI cancer patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1515\/med-2025-1260","type":"journal-article","created":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T17:57:21Z","timestamp":1756490241000},"source":"Crossref","is-referenced-by-count":2,"title":["Factors influencing hematological toxicity and adverse effects of perioperative hyperthermic intraperitoneal vs intraperitoneal chemotherapy in gastrointestinal cancer"],"prefix":"10.1515","volume":"20","author":[{"given":"Xue","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of General Practice, Beijing Friendship Hospital, Capital Medical University , Beijing , 100050 , P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhewen","family":"Zheng","sequence":"additional","affiliation":[{"name":"National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College , Shenzhen , 518116 , P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy, Shaanxi Province People\u2019s Hospital , Xi\u2019an , Shaanxi, 710068 , P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziqi","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of General Practice, Beijing Friendship Hospital, Capital Medical University , Beijing , 100050 , P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Xuanwu Hospital Capital Medical University , Beijing , 100053 , P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2025,8,29]]},"reference":[{"key":"2026022521023620274_j_med-2025-1260_ref_001","doi-asserted-by":"crossref","unstructured":"Cashin PH, Graf W, Nygren P, Mahteme H. Cytoreductive surgery and intraperitoneal chemotherapy for colorectal peritoneal carcinomatosis: Prognosis and treatment of recurrences in a cohort study. Eur J Surg Oncol (EJSO). 2012;38(6):509\u201315.","DOI":"10.1016\/j.ejso.2012.03.001"},{"key":"2026022521023620274_j_med-2025-1260_ref_002","doi-asserted-by":"crossref","unstructured":"Wei J, Wu ND, Liu BR. Regional but fatal: Intraperitoneal metastasis in gastric cancer. World J Gastroenterol. 2016;22(33):7478\u201385.","DOI":"10.3748\/wjg.v22.i33.7478"},{"key":"2026022521023620274_j_med-2025-1260_ref_003","doi-asserted-by":"crossref","unstructured":"Thomassen I, Gestel Y, Ramshorst BV, Luyer M, Bosscha K, Nienhuijs SW, et al. Peritoneal carcinomatosis of gastric origin: A population-based study on incidence, survival and risk factors. Int J Cancer. 2014;134(3):622\u20138.","DOI":"10.1002\/ijc.28373"},{"key":"2026022521023620274_j_med-2025-1260_ref_004","doi-asserted-by":"crossref","unstructured":"Sun J, Song Y, Wang Z, Gao P, Chen X, Xu Y, et al. Benefits of hyperthermic intraperitoneal chemotherapy for patients with serosal invasion in gastric cancer: a meta-analysis of the randomized controlled trials. BMC Cancer. 2012;12(1):1\u201310.","DOI":"10.1186\/1471-2407-12-526"},{"key":"2026022521023620274_j_med-2025-1260_ref_005","doi-asserted-by":"crossref","unstructured":"Sleightholm R, Watley D, Wahlmeier S, Patel A, Foster JM. The efficacy of dextran-40 as a venous thromboembolism prophylaxis strategy in cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Am Surg. 2017;83(2):134\u201340.","DOI":"10.1177\/000313481708300212"},{"key":"2026022521023620274_j_med-2025-1260_ref_006","doi-asserted-by":"crossref","unstructured":"Zhu L, Xu Y, Shan Y, Zheng R, Wu Z, Ma S. Intraperitoneal perfusion chemotherapy and whole abdominal hyperthermia using external radiofrequency following radical D2 resection for treatment of advanced gastric cancer. Int J Hyperth. 2019;36(1):403\u20137.","DOI":"10.1080\/02656736.2019.1579372"},{"key":"2026022521023620274_j_med-2025-1260_ref_007","doi-asserted-by":"crossref","unstructured":"Shang A, Wang S, Yang Y, Li L, Zhao Z, Li D, et al. Effect and safety of intraoperative intraperitoneal chemotherapy on patients suffering from colorectal cancer. World J Surg Oncol. 2021;19(1):84.","DOI":"10.1186\/s12957-021-02197-3"},{"key":"2026022521023620274_j_med-2025-1260_ref_008","doi-asserted-by":"crossref","unstructured":"Quere P, Facy O, Manfredi S, Jooste V, Faivre J, Lepage C, et al. Epidemiology, management, and survival of peritoneal carcinomatosis from colorectal cancer: A population-based study. Dis Colon Rectum. 2015;58(8):743\u201352.","DOI":"10.1097\/DCR.0000000000000412"},{"key":"2026022521023620274_j_med-2025-1260_ref_009","doi-asserted-by":"crossref","unstructured":"Lu Z, Wang J, Wientjes MG, Au LS. Intraperitoneal therapy for peritoneal cancer. Future Oncol. 2010;6(10):1625\u201341.","DOI":"10.2217\/fon.10.100"},{"key":"2026022521023620274_j_med-2025-1260_ref_010","unstructured":"Jian-Yu WU, Hou MX, Cheng HD, Jia LL. Advances in intraperitoneal chemotherapy for gastrointestinal tumors. World Latest Med Inf. 2019."},{"key":"2026022521023620274_j_med-2025-1260_ref_011","unstructured":"Zhang J, Guo Y, Wang W, Jing LI, Peng HE, Li-Shu YU, et al. Effect of laparoscopic radical gastrectomy and open radical gastrectomy on inflammatory reaction and immune function in patients with gastric cancer. Chin J Clin Oncol Rehabil. 2016."},{"key":"2026022521023620274_j_med-2025-1260_ref_012","unstructured":"Meng LJ, Zhang XR, Yang BJ. Meta analysis on the therapeutic effect of gastric cancer with fluorouracil implants. Chin J Curr Adv Gen Surg. 2016."},{"key":"2026022521023620274_j_med-2025-1260_ref_013","doi-asserted-by":"crossref","unstructured":"Amira G, Morsi A, Fayek IS, Mansour O, Nader H. Hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy in recurrent platinum-sensitive ovarian cancer NCI case control study. Asian Pac J Cancer Prev: APJCP. 2019;20(2):621\u20137.","DOI":"10.31557\/APJCP.2019.20.2.621"},{"key":"2026022521023620274_j_med-2025-1260_ref_014","unstructured":"Luk KH, Hulse RM, Phillips TL. Hyperthermia in cancer therapy. West J Med. 1980;132(3):179."},{"key":"2026022521023620274_j_med-2025-1260_ref_015","doi-asserted-by":"crossref","unstructured":"Somashekhar SP, Yethadka R, Kumar CR, Ashwin KR, Zaveri S, Rauthan A. Toxicity profile of chemotherapy agents used in cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal surface malignancies. Eur J Surg Oncol: J Eur Soc Surg Oncol Br Assoc Surg Oncol. 2020;46(4 Pt A):577\u201381.","DOI":"10.1016\/j.ejso.2019.10.032"},{"key":"2026022521023620274_j_med-2025-1260_ref_016","doi-asserted-by":"crossref","unstructured":"Cashin PH, Graf W, Nygren P, Mahteme H. Intraoperative hyperthermic versus postoperative normothermic intraperitoneal chemotherapy for colonic peritoneal carcinomatosis: A case\u2013control study. Ann Oncol. 2012;23(3):647\u201352.","DOI":"10.1093\/annonc\/mdr301"},{"key":"2026022521023620274_j_med-2025-1260_ref_017","doi-asserted-by":"crossref","unstructured":"Zheng Z, Yu H, Xiong B, Shen S, Yang H, Zhou Y. The incidence and risk factors of hepatotoxicity induced by perioperative hyperthermic intraperitoneal chemotherapy in gastrointestinal carcinoma patients: a retrospective study. OncoTargets Ther. 2018;11:5715\u201322.","DOI":"10.2147\/OTT.S170398"},{"key":"2026022521023620274_j_med-2025-1260_ref_018","doi-asserted-by":"crossref","unstructured":"Abdel-Rahman O. Effect of body mass index on 5-FU-based chemotherapy toxicity and efficacy among patients with metastatic colorectal cancer; A pooled analysis of 5 randomized trials. Clin Colorectal Cancer. 2019;18(4):e385\u201393.","DOI":"10.1016\/j.clcc.2019.07.005"},{"key":"2026022521023620274_j_med-2025-1260_ref_019","doi-asserted-by":"crossref","unstructured":"de Witte P, de Witt CA, van de Minkelis JL, Boerma D, Solinger HF, Hack CE, et al. Inflammatory response and optimalisation of perioperative fluid administration during hyperthermic intraoperative intraperitoneal chemotherapy surgery. J Gastrointest Oncol. 2019;10(2):244\u201353.","DOI":"10.21037\/jgo.2018.12.09"},{"key":"2026022521023620274_j_med-2025-1260_ref_020","doi-asserted-by":"crossref","unstructured":"Meneses do R\u00eago AC, Ara\u00fajo-Filho I. Assessing the impact of hyperthermic intraperitoneal chemotherapy on anastomotic integrity after cytoreductive surgery in gastrointestinal malignancies. Eur J Clin Med. 2024;5(5):7\u201313.","DOI":"10.24018\/clinicmed.2024.5.5.351"},{"key":"2026022521023620274_j_med-2025-1260_ref_021","doi-asserted-by":"crossref","unstructured":"Dranichnikov P, Mahteme H, Cashin PH, Graf W. Coagulopathy and venous thromboembolic events following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Ann Surg Oncol. 2021;28(12):7772\u201382.","DOI":"10.1245\/s10434-021-09941-9"},{"key":"2026022521023620274_j_med-2025-1260_ref_022","doi-asserted-by":"crossref","unstructured":"Wu Z, Chen Y, Jiang D, Pan Y, Tang T, Ma Y, et al. Mitochondrial-related drug resistance lncRNAs as prognostic biomarkers in laryngeal squamous cell carcinoma. Discov Oncol. 2024;15(1):785.","DOI":"10.1007\/s12672-024-01690-x"},{"key":"2026022521023620274_j_med-2025-1260_ref_023","doi-asserted-by":"crossref","unstructured":"Zeng X, Wu Z, Pan Y, Ma Y, Chen Y, Zhao Z. Effects of micronutrients and macronutrients on risk of allergic disease in the European population: A Mendelian randomization study. Food Agric Immunol. 2024;35(1):2442369.","DOI":"10.1080\/09540105.2024.2442369"},{"key":"2026022521023620274_j_med-2025-1260_ref_024","doi-asserted-by":"crossref","unstructured":"Shu Y, Li KJ, Sulayman S, Zhang ZY, Ababaike S, Wang K, et al. Predictive value of serum calcium ion level in patients with colorectal cancer: A retrospective cohort study. World J Gastrointest Surg. 2025;17(3):102638.","DOI":"10.4240\/wjgs.v17.i3.102638"},{"key":"2026022521023620274_j_med-2025-1260_ref_025","doi-asserted-by":"crossref","unstructured":"Chen Y, Zhang B, Wang X, Chen Y, Anwar M, Fan J, et al. Prognostic value of preoperative modified Glasgow prognostic score in predicting overall survival in breast cancer patients: A retrospective cohort study. Oncol Lett. 2025;29(4):180.","DOI":"10.3892\/ol.2025.14926"},{"key":"2026022521023620274_j_med-2025-1260_ref_026","doi-asserted-by":"crossref","unstructured":"Li K, Zeng X, Zhang Z, Wang K, Pan Y, Wu Z, et al. Pan\u2011immune\u2011inflammatory values predict survival in patients after radical surgery for non\u2011metastatic colorectal cancer: A retrospective study. Oncol Lett. 2025;29(4):197.","DOI":"10.3892\/ol.2025.14943"},{"key":"2026022521023620274_j_med-2025-1260_ref_027","doi-asserted-by":"crossref","unstructured":"Wang K, Li K, Zhang Z, Zeng X, Sulayman S, Ababaike S, et al. Prognostic value of combined NP and LHb index with absolute monocyte count in colorectal cancer patients. Sci Rep. 2025;15(1):8902.","DOI":"10.1038\/s41598-025-94126-7"}],"container-title":["Open Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/med-2025-1260\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/med-2025-1260\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T21:02:47Z","timestamp":1772053367000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/med-2025-1260\/html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,1]]},"references-count":27,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,8,29]]},"published-print":{"date-parts":[[2025,8,29]]}},"alternative-id":["10.1515\/med-2025-1260"],"URL":"https:\/\/doi.org\/10.1515\/med-2025-1260","relation":{},"ISSN":["2391-5463"],"issn-type":[{"value":"2391-5463","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,1]]},"article-number":"20251260"}}