A Four-Inflow Construction to Ensure Thermal Stability and Uniformity during Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Rats

Abstract

Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery (CRS) is used for treating peritoneal metastases of various origins. Present HIPEC protocols have rarely been validated for relevant parameters such as optimal agent, duration and perfusate temperature. In vitro experiments are not completely representative of clinical circumstances. Therefore, a good preclinical in vivo HIPEC model is needed in which temperature distributions can be well-controlled and are stable throughout treatments. Methods: We designed a setup able to generate and maintain a homogeneous flow during a 90-min HIPEC procedure using our in-house developed treatment planning tools and computer aided design (CAD) techniques. Twelve rats were treated with heated phosphate-buffered saline (PBS) using two catheter setups (one vs. four- inflows) and extensive thermometry. Simulated and measured thermal distribution and core temperatures were evaluated for the different setups. Results: Overall, the four-inflow resulted in more stable and more homogeneous thermal distributions than the one-inflow, with lower standard deviations (0.79 °C vs. 1.41 °C at the outflow, respectively) and less thermal losses. The average thermal loss was 0.4 °C lower for rats treated with the four-inflow setup. Rat core temperatures were kept stable using occasional tail cooling, and rarely exceeded 39 °C. Conclusion: Increasing the number of inflow catheters from one to four resulted in increased flow and temperature homogeneity and stability. Tail cooling is an adequate technique to prevent rats from overheating during 90-min treatments. This validated design can improve accuracy in future in vivo experiments investigating the impact of relevant parameters on the efficacy of different HIPEC protocols.

Clinical Analysis of Gut Barrier Dysfunction in Patients with Advanced Colorectal Cancer Undergoing Cytoreductive Surgery and HIPEC

“…Indeed, in most clinical trials and animal experiments, the application of HIPEC is associated with the low incidence of postoperative complications, low mortality, and better survival rate [10][11][12]. The present study also supports this notion.…”

Preclinical In Vivo-Models to Investigate HIPEC; Current Methodologies and Challenges

“…Depending on the origin of the used cancer cells, rat and mouse strains were chosen. The following rat types were used in the analyzed articles; Wistar (21%) [ 32 , 45 , 46 , 62 , 63 , 64 ], Sprague Dawley (32%) [ 40 , 43 , 51 , 52 , 57 , 65 , 66 , 67 , 68 ], WAG/Rij (32%) [ 47 , 54 , 69 , 70 , 71 , 72 , 73 , 74 , 75 ] and athymic/nude (14%) [ 44 , 76 , 77 , 78 ] rats. For mouse experiments, the following strains were used: Swiss albino (20%) [ 36 , 38 , 79 ], athymic (33%) [ 37 , 48 , 50 , 55 , 80 ], C57BL/6 (20%) [ 33 , 39 , 81 ], BALB/c (20%) [ 49 , 56 , 82 ] and NOD-SCID (7%) [ 34 ].…”

“…In a previous study, HIPEC treatments in rats were simulated at various flow rates. Doubling the flow rate increased the thermal homogeneity while halving the flow rate resulted in increased thermal heterogeneity [ 76 , 95 ]. Higher flow rates tend to increase the homogeneity, but also the core temperature.…”

“…Maximizing flow rates, while maintaining a tolerable core temperature should be preferred. Increasing the number of inflows catheters from 1 to 4 increased the thermal homogeneity and the stability of inflow temperatures in rats [ 76 ]. The placement of the catheters can also increase the distribution of the heated fluid.…”

“…Almost all evaluated studies featured one inflow and one outflow. Only one study considered more catheters in a rat model [ 76 ], nine in swine/pig models [ 53 , 58 , 60 , 85 , 86 , 87 , 88 , 89 , 90 ], and one in a mouse model [ 56 ]. More inflow catheters showed a higher and more uniform perfusion temperature in rats.…”