Risk of Acute Kidney Injury Following Mytomicin C Resorption during Hyperthermic Intraperitoneal Chemotherapy

Main Article Content

Piet de Witte Peter Bruins Djamila Boerma Veronique Kemmel

Abstract

Background:     Surgical cytoreduction and simultaneous hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) is a common treatment for peritoneal carcinomatosis. During intraperitoneal chemotherapy, mitomycin C is frequently used. Mitomycin C is known to be nephrotoxic. Little is known about the effect of systemically absorbed mitomycin C on renal function during HIPEC surgery.


Methods: In twenty-two patients undergoing cytoreductive surgery and HIPEC for peritoneal carcinomatosis the systemic levels of mitomycin C were measured in plasma. The relation of plasma levels of mitomycin C with duration of surgery and complexity of surgery was evaluated.


Furthermore, we evaluated the relation between systemic mitomycin C levels with renal function.


Results Two patients of the total of 22 patients developed acute kidney injury. In these patients, preoperative creatinine level increased from (1) 109 μmol/L to maximum 890 μmol/L on the 6th postoperative day after which renal replacement therapy was started and (2) from 67 μmol/L to 213 μmol/L. Whereas maximum plasma levels of mitomycin C in these 2 patients were 145 μg/L and 280 μg/L compared to the levels in the other patients (167 μg/L ±80.8). Peak levels of plasma creatinine were on post operative day 2. None of the other patients needed renal replacement therapy. Eight patients showed significant increase of plasma creatinine levels, i.e. >20% increase from preoperative values. We did not observe a correlation between complexity of surgery, increased absorption of mitomycin C, higher mitomycin C plasma levels and signs of kidney injury.


Conclusions:     Systemic absorption of mitomycin C during HIPEC surgery is independent to extension of cytoreductive surgery and duration of surgery. In this small study group, we observed an impairment of renal function which may be related to systemic absorption of mitomycin C. Further research is warranted to answer possible association of mitomycin C levels in patients at risk for development of AKI.

Keywords: Mitomycin, HIPEC, cytoreductive surgery, renal function, kidney injury, AKI

Article Details

How to Cite
WITTE, Piet de et al. Risk of Acute Kidney Injury Following Mytomicin C Resorption during Hyperthermic Intraperitoneal Chemotherapy. Medical Research Archives, [S.l.], v. 11, n. 7.2, july 2023. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/4181>. Date accessed: 15 may 2024. doi: https://doi.org/10.18103/mra.v11i7.2.4181.
Section
Research Articles

References

1. Koga S, Hamazoe R, Maeta M, Shimizu N, Murakami A, Wakatsuki T. Prophylactic therapy for peritoneal recurrence of gastric cancer by continuous hyperthermic peritoneal perfusion with mitomycin C. Cancer. 1988;61(2). doi:10.1002/1097-0142(19880115)61:2<232::aid-cncr2820610205>3.0.co;2-u
2. Seshadri RA, Glehen O. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in gastric cancer. World J Gastroenterol. 2016;22(3). doi:10.3748/wjg.v22.i3.1114
3. Liesenfeld LF, Wagner B, Hillebrecht HC, et al. HIPEC-Induced Acute Kidney Injury: A Retrospective Clinical Study and Preclinical Model. Ann Surg Oncol. 2022;29(1):139-151. doi:10.1245/s10434-021-10376-5
4. Braam HJ, Boerma D, Wiezer MJ, van Ramshorst B. Cytoreductive surgery and HIPEC in treatment of colorectal peritoneal carcinomatosis: experiment or standard care? A survey among oncologic surgeons and medical oncologists. Int J Clin Oncol. 2015;20(5):928-934. doi:10.1007/s10147-015-0816-5
5. Sugarbaker PH, van der Speeten K. Surgical technology and pharmacology of hyperthermic perioperative chemotherapy. J Gastrointest Oncol. 2016;7(1). doi:10.3978/j.issn.2078-6891.2015.105
6. de Bree E, Michelakis D, Stamatiou D, Romanos J, Zoras O. Pharmacological principles of intraperitoneal and bidirectional chemotherapy. Pleura Peritoneum. 2017;2(2):47-62. doi:10.1515/pp-2017-0010
7. González-Moreno S, González-Bayón LA, Ortega-Pérez G. Hyperthermic intraperitoneal chemotherapy: Rationale and technique. World J Gastrointest Oncol. 2010;2(2). doi:10.4251/wjgo.v2.i2.68
8. Kemmel V, Mercoli HA, Meyer N, et al. Mitomycin C Pharmacokinetics as Predictor of Severe Neutropenia in Hyperthermic Intraperitoneal Therapy. Ann Surg Oncol. 2015;22 Suppl 3. doi:10.1245/s10434-015-4679-9
9. Katz MH, Barone RM. The rationale of perioperative intraperitoneal chemotherapy in the treatment of peritoneal surface malignancies. Surg Oncol Clin N Am. 2003;12(3).
doi:10.1016/s1055-3207(03)00034-6
10. Stewart JH, Shen P, Russell GB, et al. Appendiceal neoplasms with peritoneal dissemination: outcomes after cytoreductive surgery and intraperitoneal hyperthermic chemotherapy. Ann Surg Oncol. 2006;13(5). doi:10.1007/s10434-006-9708-2
11. Lambert LA, Armstrong TS, Lee JJ, et al. Incidence, risk factors, and impact of severe neutropenia after hyperthermic intraperitoneal mitomycin C. Ann Surg Oncol. 2009;16(8):2181-2187. doi:10.1245/s10434-009-0523-4
12. Valavaara R, Nordman E. Renal complications of mitomycin C therapy with special reference to the total dose. Cancer. 1985;55(1). doi:10.1002/1097-0142(19850101)55:1<47::aid-cncr2820550108>3.0.co;2-#
13. Habib SL, Rojna M. Diabetes and risk of cancer. ISRN Oncol. 2013;2013. doi:10.1155/2013/583786
14. Randle RW, Ahmed S, Levine EA, et al. Significance of diabetes on morbidity and mortality following cytoreductive surgery with hyperthermic intraperitoneal chemotherapy. J Surg Oncol. 2015;111(6). doi:10.1002/jso.23865
15. de Witte P, de Witt CA, van de Minkelis JL, et al. Inflammatory response and optimalisation of perioperative fluid administration during hyperthermic intraoperative intraperitoneal chemotherapy surgery. J Gastrointest Oncol. 2019;10(2). doi:10.21037/jgo.2018.12.09
16. Sugarbaker PH, Graves T, DeBruijn EA, et al. Early postoperative intraperitoneal chemotherapy as an adjuvant therapy to surgery for peritoneal carcinomatosis from gastrointestinal cancer: pharmacological studies. Cancer Res. 1990;50(18).
17. Witkamp AJ, de Bree E, van Goethem R, Zoetmulder FA. Rationale and techniques of intra-operative hyperthermic intraperitoneal chemotherapy. Cancer Treat Rev. 2001;27(6):365-374. doi:10.1053/ctrv.2001.0232
18. Jonker G, Hoogenboom LJ, van Ramshorst B, Bruins P. Atracurium during induced hyperthermia. J Anesth. 2009;23(3):442-444. doi:10.1007/s00540-009-0773-0
19. den Hartigh J, van Oort WJ, Hulshoff A. Liquid chromatographic determination of mitomycin C in human plasma and urine. J Chromatogr. 1984;306:444-445. doi:10.1016/s0378-4347(00)80914-7
20. Eksborg S, Ehrsson H, Lindfors A. Liquid chromatographic determination of mitomycin C in human plasma and urine. J Chromatogr. 1983;274:263-270. doi:10.1016/s0378-4347(00)84429-1
21. Barbhaiya RH, Papp EA, van Harken DR, Smyth RD. Pharmacokinetics of mitomycin C in dogs: Application of a high‐performance liquid chromatographic assay. J Pharm Sci. 1984;73(9). doi:10.1002/jps.2600730909
22. Brandstrup B, Tønnesen H, Beier-Holgersen R, et al. Effects of Intravenous Fluid Restriction on Postoperative Complications: Comparison of Two Perioperative Fluid Regimens - A Randomized Assessor-Blinded Multicenter Trial. Ann Surg. 2003;238(5). doi:10.1097/01.sla.0000094387.50865.23
23. Kitayama J, Emoto S, Yamaguchi H, et al. Flow cytometric quantification of intraperitoneal free tumor cells in patients with peritoneal metastasis. Cytometry B Clin Cytom. 2014;86(1). doi:10.1002/cyto.b.21126
24. Kodera Y, Nakanishi H, Ito S, et al. Quantitative detection of disseminated cancer cells in the greater omentum of gastric carcinoma patients with real-time RT-PCR: A comparison with peritoneal lavage cytology. Gastric Cancer. 2002;5(2). doi:10.1007/s101200200012
25. van Ruth S, Verwaal VJ, Zoetmulder FA. Pharmacokinetics of intraperitoneal mitomycin C. Surg Oncol Clin N Am. 2003;12(3). doi:10.1016/s1055-3207(03)00031-0
26. Dagel T, Misirlioglu S, Tanju S, et al. Hyperthermic intraperitoneal chemotherapy is an independent risk factor for development of acute kidney injury. Journal of BUON. 2018;23(5).
27. Sin EIL, Chia CS, Tan GHC, Soo KC, Teo MCC. Acute kidney injury in ovarian cancer patients undergoing cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy. International Journal of Hyperthermia. 2017;33(6):690-695. doi:10.1080/02656736.2017.1293304
28. Schmidt C, Creutzenberg M, Piso P, Hobbhahn J, Bucher M. Peri-operative anaesthetic management of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy. Anaesthesia. 2008;63(4). doi:10.1111/j.1365-2044.2007.05380.x
29. Kapoor R, Robinson KA, Cata JP, et al. Assessment of nephrotoxicity associated with combined cisplatin and mitomycin C usage in laparoscopic hyperthermic intraperitoneal chemotherapy. Int J Hyper-thermia. 2019;36(1). doi:10.1080/02656736.2019.1597175