Abstract
Background
Infectious postoperative complications often delay systemic chemotherapy after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CS-HIPEC). Because the authors have empirically observed fewer incisional infectious complications than expected after CS-HIPEC with mitomycin C (MMC), they investigated the antimicrobial properties of HIPEC perfusate fluid.
Methods
This study prospectively measured in vitro bacterial growth inhibition by HIPEC perfusate (n = 18). After 10 µL of perfusate had been plated on agar plate inoculated by standard strains of either Escherichia coli (strain 25922) or Staphylococcus aureus (strain 25923), it was incubated at 37 °C for 24 h. Antimicrobial activity evidenced by a zone of complete growth inhibition was measured in millimeters. These were compared against growth inhibition produced by control groups represented by MMC solution in normal saline (MMC concentrations of 2, 4, 6, 8, and 8.75 µg/mL), 7 per group.
Results
Bacterial inhibition by HIPEC perfusate was stronger against E. coli than against S. aureus (13.1 ± 6.8 vs 8.3 ± 7.7 mm; p = 0.005). No E. coli inhibition was observed for MMC saline in concentrations of 2 through 8 µg/mL (p < 0.001 each), and inhibition of 4.5 ± 5.7 mm was observed for an MMC saline concentration of 8.75 µg/mL (p = 0.007). The S. aureus inhibition zones by MMC saline solutions were 2.2 ± 2.1 (p = 0.002), 5.1 ± 2.3 (p = 0.135), 7.5 ± 1.0 (p = 0.654), 9.6 ± 0.9 (p = 0.058), and 10.2 ± 0.4 mm (p = 0.021).
Conclusion
The antimicrobial properties of HIPEC perfusate are considerable but variable between patients and stronger against E. coli than against S. aureus. Further studies of HIPEC carrier solutions and chemotherapy agents may result in reduction of surgical-site infection and thus enhanced patient recovery.
Similar content being viewed by others
References
Wasserman DW, Boulos M, Hopman WM, Booth CM, Goodwin R, Biagi JJ. Reasons for delay in time to initiation of adjuvant chemotherapy for colon cancer. J Oncol Pract. 2015;11:e28–35.
Franko J, Gusani NJ, Holtzman MP, et al. Multivisceral resection does not affect morbidity and survival after cytoreductive surgery and chemoperfusion for carcinomatosis from colorectal cancer. Ann Surg Oncol. 2008;15:3065–72.
Gusani NJ, Cho SW, Colovos C, et al. Aggressive surgical management of peritoneal carcinomatosis with low mortality in a high-volume tertiary cancer center. Ann Surg Oncol. 2008;15:754–63.
Elias D, Goere D, Blot F, et al. Optimization of hyperthermic intraperitoneal chemotherapy with oxaliplatin plus irinotecan at 43 degrees C after compete cytoreductive surgery: mortality and morbidity in 106 consecutive patients. Ann Surg Oncol. 2007;14:1818–24.
Bodet CA III, Jorgensen JH, Drutz DJ. Antibacterial activities of antineoplastic agents. Antimicrob Agents Chemother. 1985;28:437–39.
Michel J, Jacobs JY, Sacks T. Bactericidal effect of combinations of antimicrobial drugs and antineoplastic antibiotics against Gram-negative bacilli. Antimicrob Agents Chemother. 1979;16:761–66.
Ueda Y, Saito A, Fukuoka Y, et al. Interactions of beta-lactam antibiotics and antineoplastic agents. Antimicrob Agents Chemother. 1983;23:374–78.
Franko J, Ibrahim Z, Gusani NJ, Holtzman MP, Bartlett DL, Zeh HJ III. Cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion versus systemic chemotherapy alone for colorectal peritoneal carcinomatosis. Cancer. 2010;116:3756–62.
Verwaal VJ, van Ruth S, de Bree E, 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 Oncol. 2003;21:3737–43.
Cubukcu A, Alponat A, Gonullu NN. Mitomycin-C prevents reformation of intraabdominal adhesions after adhesiolysis. Surgery. 2002;131:81–84.
van Ruth S, Verwaal VJ, Zoetmulder FA. Pharmacokinetics of intraperitoneal mitomycin C. Surg Oncol Clin North Am. 2003;12:771–80.
Sugarbaker PH, Stuart OA, Carmignani CP. Pharmacokinetic changes induced by the volume of chemotherapy solution in patients treated with hyperthermic intraperitoneal mitomycin C. Cancer Chemother Pharmacol. 2006;57:703–08.
Francescutti V, Rivera L, Seshadri M, et al. The benefit of intraperitoneal chemotherapy for the treatment of colorectal carcinomatosis. Oncol Rep. 2013;30:35–42.
Acknowledgment
The authors are thankful to the staff of the Departments of Pathology, Surgery and Pharmacy at the Mercy Medical Center in Des Moines for their assistance.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Lange, K.N., McKay, D., Gentry, B.G. et al. Antimicrobial Properties of Perfusate Fluid After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CS-HIPEC) with Mitomycin C. Ann Surg Oncol 24, 3837–3841 (2017). https://doi.org/10.1245/s10434-017-6113-y
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1245/s10434-017-6113-y