Cooney Olivia S, Goodin Dylan A, Mouw Tyler J, Martin Robert C G, Frieboes Hermann B
Department of Bioengineering, University of Louisville, Louisville, KY, USA.
Department of Surgery, University of Louisville, Louisville, KY, USA.
J Gastrointest Oncol. 2024 Aug 31;15(4):1847-1860. doi: 10.21037/jgo-24-352. Epub 2024 Aug 28.
Hyperthermic intraperitoneal chemotherapy (HIPEC) targets intraperitoneal tumors with heated drug solutions via catheters inserted into the peritoneal space. Although studies have focused on clinical outcomes, the flow dynamics at specific intra-abdominal locations at-risk of harboring malignant cells remain poorly understood but are likely to impact the drug pharmacokinetics. Consequently, optimal protocols remain uncertain, with efficacy critically dependent on drug temperature and flow rate. This study tested the hypothesis that fluid flow dynamics at specific at-risk locations could be evaluated via a computational fluid dynamics (CFD) model of closed HIPEC in a simulated human abdominal cavity, with the goal to enable protocol optimization.
A computer-aided-design (CAD) model of a human intraperitoneal cavity (30 L) was coupled with computational fluid dynamics analysis. The tested HIPEC cycle parameters included catheter position and flow rates. The cavity was subjected to forward (superior to inferior flow) or reverse flow directions at 800 or 1,120 cc/min through four catheters, two as inlets and two as outlets, placed in upper and lower abdominal positions (net fluid volume: 18.5 L). Probes to measure temperature and flow were simulated between small and large bowels, inferior to small bowel mesentery, next to duodenum, superior to liver, superior to fundus, posterior to stomach, and posterior to liver.
The simulations highlight heterogeneity in temperatures and flow that may occur during HIPEC at particular at-risk locations as a function of chemotherapy flow rate and direction. Temperature and fluid flow over the course of 90 min respectively varied from 0.93 K and <0.001 m/s inferior to small bowel mesentery (800 cc/min forward flow) to 3.6 K and 0.01 m/s next to the duodenum (either 800 or 1,120 cc/min forward flow). The results further suggest that monitoring outflow temperature may be inadequate for assessing HIPEC performance at at-risk locations.
Without intra-abdominal temperature monitoring at at-risk locations, it may be unfeasible to determine whether target temperatures and temperature homogeneity are being achieved during HIPEC. This work demonstrates that computational analysis offers the capability to monitor intra-abdominal locations at-risk of suboptimal heating and fluid flow given specific HIPEC parameters, and represents a first step towards designing efficacious tumor targeting during HIPEC.
热灌注化疗（HIPEC）通过插入腹膜腔的导管，利用加热的药物溶液靶向治疗腹膜内肿瘤。尽管研究主要关注临床结果，但对于腹腔内特定存在癌细胞风险部位的流体动力学仍知之甚少，而这可能会影响药物的药代动力学。因此，最佳方案仍不确定，疗效严重依赖于药物温度和流速。本研究检验了这样一个假设，即可以通过模拟人体腹腔内封闭热灌注化疗的计算流体动力学（CFD）模型来评估特定风险部位的流体流动动力学，目的是实现方案优化。
将人体腹腔（30升）的计算机辅助设计（CAD）模型与计算流体动力学分析相结合。测试的热灌注化疗周期参数包括导管位置和流速。通过四个导管，两个作为入口，两个作为出口，放置在上腹部和下腹部位置（净液体体积：18.5升），使腹腔以800或1120毫升/分钟的流速进行正向（从上到下流动）或反向流动。在小肠和大肠之间、小肠系膜下方、十二指肠旁、肝脏上方、胃底上方、胃后方和肝脏后方模拟了测量温度和流量的探头。
模拟结果突出显示了热灌注化疗期间，在特定风险部位可能出现的温度和流量的异质性，这是化疗流速和方向的函数。在90分钟的过程中，温度和流体流速分别从小肠系膜下方（800毫升/分钟正向流动）的0.93开尔文和<0.001米/秒变化到十二指肠旁（800或1120毫升/分钟正向流动）的3.6开尔文和0.01米/秒。结果进一步表明，监测流出温度可能不足以评估热灌注化疗在风险部位的性能。
如果不在风险部位进行腹腔内温度监测，可能无法确定在热灌注化疗期间是否达到了目标温度和温度均匀性。这项工作表明，计算分析能够在给定特定热灌注化疗参数的情况下，监测腹腔内存在加热和流体流动不理想风险的部位，这是朝着在热灌注化疗期间设计有效的肿瘤靶向迈出的第一步。
