Document Type : Review articles


1 Department of Obstetrics and Gynecology, Faculty of Medicine, Malatya Turgut Ozal University, Malatya, Turkey

2 Department of Obstetrics and Gynecology, Faculty of Medicine, ?nonu University, Malatya, Turkey


Background: Hyperthermic intraperitoneal administration of chemotherapy (HIPEC) targets microscopic residues remaining after complete cytoreduction.
Objectives: We systematically presented the development process of the HIPEC treatment regimen, the most remarkable publications on this topic, the most productive countries, and the future of treatment in the coming years.
Methods: The source of our study was the Web of Science (WoS) database which included the Korean Journal Database, core collection index, Russian Science Citation Index, and Sci ELO citation index.
Results: We reached a total of 3,343 publications by analyzing the WoS database using the keyword of "Hyperthermic intraperitoneal chemotherapy". When the citations of the documents written about HIPEC were evaluated, we found that the highest citation was made in 2019. Co-citation analysis showed that there were 27,724 authors investigating the issue of HIPEC. The most active university was determined as Wake Forest University, USA. Collaboration and citation collaboration was observed between Wake Forest University, the University of Pittsburgh, and the University of Texas. The intersection point of all researcher countries was the USA. While reviewing the articles on HIPEC, we also identified new trends and topics in this regard. Ovarian cancers, gastric cancers, and colorectal cancers were found to be the types of cancer that had the strongest relationship with HIPEC.
Conclusion: HIPEC therapies should be considered an area of research that has been studied, published, and cited by surgeons, oncologists, and pharmacologists interested in the treatment of tumors with peritoneal spread.


  1. Duska LR, Kohn EC. The New classifications of ovarian, fallopian tube, and primary peritoneal cancer and their clinical implications. Ann Oncol. 2017;28(8):1-5. doi: 10.1093/annonc/mdx445. [PubMed: 29232468].
  2. Hoskins WJ. Epithelial ovarian carcinoma: principles of primary surgery. Gynecol Oncol. 1994;55(2):91-6. doi: 10.1006/gyno.1994.1346. [PubMed: 7835815].
  3. Flessner MF. The transport barrier in intraperitoneal therapy. Am J Physiol Renal Physiol. 2005;288(3):433-42. doi: 10.1152/ajprenal.00313.2004. [PubMed: 15692055].
  4. Overgaard J. Effect of hyperthermia on malignant cells in vivo. A review and a hypothesis. Cancer. 1977;39(6):2637-46. doi: 10.1002/1097-0142(197706)39:6<2637: aid-cncr2820390650>;2-s. [PubMed: 872062].
  5. Koole SN, van Driel WJ, Sonke GS. Hyperthermic intraperitoneal chemotherapy for ovarian cancer: The heat is on. Cancer. 2019;24:4587-93. doi: 10.1002/cncr.32505. [PubMed: 31967678].
  6. Vergote I, Harter P, Chiva L. Hyperthermic intraperitoneal chemotherapy does not improve survival in advanced ovarian cancer. Cancer. 2019;24:4594-97. doi: 10.1002/cncr.32496. [PubMed: 31967685].
  7. Fujimoto S, Takahashi M, Endoh F, Shrestha RD, Kokubun M, Takai M, Okui K. A clinical pilot study combining surgery with intraoperative pelvic hyperthermochemotherapy to prevent the local recurrence of rectal cancer. Ann Surg. 1991;213(1):43-7. doi: 10.1097/00000658-199101000-00008. [PubMed: 1985537].
  8. Colombo N, Sessa C, du Bois A, Ledermann J, McCluggage WG, McNeish I, et al. ESMO-ESGO consensus conference recommendations on ovarian cancer: pathology and molecular biology, early and advanced stages, borderline tumours and recurrent disease. Ann Oncol. 2019;30(5):672-705. doi: 10.1093/annonc/mdz062. [PubMed: 31046081].
  9. Verwaal VJ, van Ruth S, de Bree E, van Sloothen GW, van Tinteren H, Boot H, et al. Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer. J Clin
  10. Oncol. 2003;21(20):3737-43. doi: 10.1200/JCO.2003.04.187. [PubMed: 14551293].
  11. Van Driel WJ, Koole SN, Sikorska K, Schagen van Leeuwen JH, Schreuder HWR, Hermans RHM, et al. Hyperthermic ıntraperitoneal chemotherapy in Ovarian Cancer. N Engl J Med. 2018;378(3):230-240. doi: 10.1056/NEJMoa1708618. [PubMed: 29342393].
  12. Sahebi R, Akbari N, Bayat Z, Rashidmayvan M, Mansoori A, Beihaghi M. A Summary of Autophagy Mechanisms in Cancer Cells. Res Biotechnol Environ Sci. 2022; 1(1): 28-35. doi: 10.58803/RBES.2022.1.1.06
  13. Weitz J, Koch M, Debus J, Höhler T, Galle PR, Büchler MW. Colorectal cancer. Lancet. 2005;365(9454):153-65. doi: 10.1016/S0140-6736(05)17706-X. [PubMed: 15639298].
  14. Verwaal VJ, Bruin S, Boot H, van Slooten G, van Tinteren H. 8-year follow-up of randomized trial: cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy in patients with peritoneal carcinomatosis of colorectal cancer. Ann Surg Oncol. 2008;15(9):2426-32. doi: 10.1245/s10434-008-9966-2. [PubMed: 18521686].
  15. Elias D, Gilly F, Boutitie F, Quenet F, Bereder JM, Mansvelt B, et al. Peritoneal colorectal carcinomatosis treated with surgery and perioperative intraperitoneal chemotherapy: retrospective analysis of 523 patients from a multicentric French study. J Clin Oncol. 2010;28(1):63-8. doi: 10.1200/JCO.2009.23.9285. [PubMed: 19917863].
  16. Elias D, Lefevre JH, Chevalier J, Brouquet A, Marchal F, Classe JM, et al. Complete cytoreductive surgery plus intraperitoneal chemohyperthermia with oxaliplatin for peritoneal carcinomatosis of colorectal origin. J Clin Oncol. 2009;27(5):681-5. doi: 10.1200/JCO.2008.19.7160. [PubMed: 19103728].
  17. Chua TC, Moran BJ, Sugarbaker PH, Levine EA, Glehen O, Gilly FN, et al. Early- and long-term outcome data of patients with pseudomyxoma peritonei from appendiceal origin treated by a strategy of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. J Clin Oncol. 2012;30(20):2449-56. doi: 10.1200/JCO.2011.39.7166. [PubMed: 22614976].
  18. Sugarbaker PH. New standard of care for appendiceal epithelial neoplasms and pseudomyxoma peritonei syndrome? Lancet Oncol. 2006;7(1):69-76. doi: 10.1016/S1470-2045(05)70539-8. [PubMed: 16389186].
  19. Yan TD, Deraco M, Baratti D, Kusamura S, Elias D, Glehen O, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for malignant peritoneal mesothelioma: multi-institutional experience. J Clin Oncol. 2009;27(36):6237-42. doi: 10.1200/JCO.2009.23.9640. [PubMed: 19917862].
  20. Koppe MJ, Boerman OC, Oyen WJ, Bleichrodt RP. Peritoneal carcinomatosis of colorectal origin: incidence and current treatment strategies. Ann Surg. 2006;243(2):212-22. doi: 10.1097/01.sla.0000197702.46394.16. [PubMed: 16432354].
  21. Chua TC, Yan TD, Saxena A, Morris DL. Should the treatment of peritoneal carcinomatosis by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy still be regarded as a highly morbid procedure?: a systematic review of morbidity and mortality. Ann Surg. 2009;249(6):900-7. doi: 10.1097/SLA.0b013e3181a45d86. [PubMed: 19474692].
  22. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424. doi: 10.3322/caac.21492. [PubMed: 30207593].
  23. Jung H. Interaction of thermotolerance and thermosensitization induced in CHO cells by combined hyperthermic treatments at 40 and 43 degrees C. Radiat Res. 1982;91(3):433-46. [PubMed: 6889751].
  24. Crestani A, Benoit L, Touboul C, Pasquier J. Hyperthermic intraperitoneal chemotherapy (HIPEC): Should we look closer at the microenvironment? Gynecol Oncol. 2020;159(1):285-94. doi: 10.1016/j.ygyno.2020.07.017. [PubMed: 32732012].
  25. Chambers LM, Costales AB, Crean-Tate K, Kuznicki M, Morton M, Horowitz M, et al. A guide to establishing a hyperthermic intraperitoneal chemotherapy program in gynecologic oncology. Gynecol Oncol. 2020;158(3):794-802. doi: 10.1016/j.ygyno.2020.06.487. [PubMed: 32624234].
  26. Bouchard-Fortier G, Cusimano MC, Fazelzad R, Sajewycz K, Lu L, Espin-Garcia O, et al. Oncologic outcomes and morbidity following heated intraperitoneal chemotherapy at cytoreductive surgery for primary epithelial ovarian cancer: A systematic review and meta-analysis. Gynecol Oncol. 2020;158(1):218-28. doi: 10.1016/j.ygyno.2020.03.034. [PubMed: 32387131].
  27. Navarro-Barrios Á, Gil-Martinez J, Ramos-Bernardo I, Barrios P, Muñoz-Casares C, Torres-Melero J, et al. Intraperitoneal hyperthermic chemotherapy after cytoreduction in patients with peritoneal metastases from endometrial cancer.
  28. The next frontier? Surg Oncol. 2020;33:19-23. doi: 10.1016/j.suronc.2019.12.002.
  29. CCWG. The Chicago Consensus on peritoneal surface malignancies: Management of ovarian neoplasms. Cancer. 2020;126(11):2553-60. doi: 10.1002/cncr.32867. [PubMed: 32282068].
  30. Huo YR, Richards A, Liauw W, Morris DL. Hyperthermic intraperitoneal chemotherapy (HIPEC) and cytoreductive surgery (CRS) in ovarian cancer: a systematic review and meta-analysis. Eur J Surg Oncol. 2015;41(12):1578–89. doi: 10.1016/j.ejso.2015.08.172. [PubMed: 26453145].
  31. Rodriguez-Ortiz L, Arjona-Sanchez A, Ibañez-Rubio M, Sanchez-Hidalgo J, Casado-Adam A, Rufian-Peña S, et al. Laparoscopic cytoreductive surgery and HIPEC: a comparative matched analysis. Surg Endosc. 2021;35(4):1778-85. doi: 10.1007/s00464-020-07572-x. [PubMed: 32328823].
  32. Akladios C, Azais H, Ballester M, Bendifallah S, Bolze PA, Bourdel N, et al. Recommendations for the surgical management of gynecological cancers during the COVID-19 pandemic - FRANCOGYN group for the CNGOF. J Gynecol Obstet Hum Reprod. 2020;49(6):1-4. doi: 10.1016/j.jogoh.2020.101729. [PubMed: 32247066].
  33. Dumont F, Duchalais E, Aumont A, Thibaudeau E. Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy
  34. by laparoscopy via a single-port approach for low-grade peritoneal malignancy. Surg Endosc. 2020;34(6):2789-95. doi: 10.1007/s00464-020-07492-w. [PubMed: 32166549].
  35. Yıldırım E, Kahraman E. Thrombosis in pregnancy: Scientometric analysis of thrombotic diseases in pregnancy between 1975-2019. Ann Med Res. 2020;27(7):1893-9. doi: 10.5455/annalsmedres.2020.04.396.