Slama Alexis, Steinberg Hannah, Collaud Stéphane, Okumus Özlem, Hilger Ralph-Axel, Bauer Sebastian, Schildhaus Hans-Ulrich, Aigner Clemens, Schaarschmidt Benedikt M
Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.
Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, Essen, Germany.
Eur Radiol Exp. 2024 Dec 5;8(1):137. doi: 10.1186/s41747-024-00532-3.
Whole lung transpulmonary chemoembolization using a combination of doxorubicin (DXO) and degradable starch microspheres (DSM-TPCE) might be a promising treatment option in soft tissue sarcoma. To pave the way for clinical studies, this study aimed to evaluate the short-term effects of DSM-TPCE with DXO using an ex vivo isolated lung perfusion (ILP) model.
Nine lung specimens retrieved from patients undergoing lobectomy underwent ex vivo ILP. In groups of three, lung specimens were either treated with sole DXO, sole DSM, or combined substances (DSM + DXO). During ex vivo ILP, histological samples were obtained from each lung every 15 min. Quantitative DXO analysis and histopathological grading of possible tissue damage using a five-point Likert scale was performed. Two-way repeated measures ANOVA tested for differences between treatment groups and changes over time.
We created a preclinical ex vivo ILP model to simulate the effects of DSM-TPCE. In histopathological analysis, only two specimens, treated with only DXO, showed an increase in parenchymal damage over time. No significant effect of time (3.3%, p = 0.305) or group (23.3; p = 0.331) was identified. Within the lung tissue, the DXO concentration ranged from 205 to 1,244 ng/g. No significant effects could be detected regarding different treatment groups (4.9% of total variation, p = 0.103).
In an ex vivo ILP model using human lung lobes, the physiological effects of DSM-TPCE with DXO could be tested. Neither increased DXO concentrations in lung tissue nor histopathological changes indicating early lung toxicity were observed.
An ex vivo ILP model using human lung specimens did not show any signs of early lung toxicity after transpulmonary chemoembolization with DXO. These results support further evaluation of DSM-TPCE in phase I/II trials.
Transpulmonary chemoembolization can be investigated in an ex vivo ILP model. DSM did not increase DXO in normal lung tissue. DSM did not increase parenchymal toxicity compared to the control groups.
使用阿霉素（DXO）和可降解淀粉微球联合进行的全肺经肺动脉化疗栓塞术（DSM-TPCE）可能是软组织肉瘤一种有前景的治疗选择。为临床研究铺平道路，本研究旨在使用离体肺灌注（ILP）模型评估DSM-TPCE联合DXO的短期效果。
从接受肺叶切除术的患者中获取9个肺标本进行离体ILP。将肺标本分为三组，分别用单纯DXO、单纯DSM或联合物质（DSM + DXO）处理。在离体ILP过程中，每隔15分钟从每个肺获取组织学样本。进行DXO定量分析，并使用五点李克特量表对可能的组织损伤进行组织病理学分级。采用双向重复测量方差分析来检验治疗组之间的差异以及随时间的变化。
我们创建了一个临床前离体ILP模型来模拟DSM-TPCE的效果。在组织病理学分析中，仅两个仅用DXO处理的标本显示实质损伤随时间增加。未发现时间（3.3%，p = 0.305）或组间（23.3；p = 0.331）有显著影响。在肺组织内，DXO浓度范围为205至1244 ng/g。未检测到不同治疗组有显著影响（占总变异的4.9%，p = 0.103）。
在使用人肺叶的离体ILP模型中，可以测试DSM-TPCE联合DXO的生理效果。未观察到肺组织中DXO浓度增加，也未观察到表明早期肺毒性的组织病理学变化。
使用人肺标本的离体ILP模型在经肺动脉化疗栓塞术联合DXO后未显示任何早期肺毒性迹象。这些结果支持在I/II期试验中对DSM-TPCE进行进一步评估。
可在离体ILP模型中研究经肺动脉化疗栓塞术。DSM未增加正常肺组织中的DXO。与对照组相比，DSM未增加实质毒性。
