Caren van Roekel

275 Discussion It was hypothesized that the use of an anti-reflux catheter could lead to higher response rates by improving the T/N ratio. An improved T/N ratio means that the ratio between absorbed-dose in the tumors versus the parenchyma is favorable, with a high tumor-absorbed dose and a low parenchymal-absorbed dose. The manufacturer of the Surefire® (TriSalus Life Sciences, Westminster, CO, USA) anti-reflux catheter claims that this catheter can effectuate an improved T/N ratio by inducing a more homogeneous distribution of the microspheres. Due to the expandable tip, the laminar flow columns are disrupted and a turbulent particle flow pattern is induced (93). Also, due to the expandable tip, a decrease in blood pressure in the downstream vascular territory can be observed, which would lead to a higher infusion efficiency with higher tumor deposition compared with surrounding healthy liver tissue (94, 95). In a retrospective study of 88 hepatocellular carcinoma patients, the use of a standard end-hole catheter versus an anti-reflux catheter in transarterial chemoembolization was investigated. Explant analysis showed a higher T/N ratio with the use of an anti-reflux catheter (89% versus 55% intra-tumoral microsphere deposition) and a higher percentage tumor necrosis in the anti- reflux catheter group (89.0% versus 56.1%) (96). In our study, the SIM study, we did not find a significant difference in tumor to non-tumor activity concentration ratio. Moreover, these innovative catheters were not easy to use, since they often induced vasospasm. Hence, we cannot recommend the use of this type of anti-reflux catheters to increase T/N ratios. It may be different however, for balloon-catheters such as the Occlusafe® (Terumo). This type of catheter fully occludes the vascular lumen, possibly leading to a reversal of flow towards the tumors in the peripheral vasculature due to the downstream hypotension. Besides anti-reflux catheters, T/N ratios may also be improved pharmacologically, for instance by using angiotensin II. Tumor vessels are not well developed, with an immature smooth muscle compartment of the vessel wall and immature neurovascular innervation. Therefore, they do not respond to the infusion of a vasoconstrictive agent, whereas the vasculature of the healthy liver tissue does. This leads to an increase in preferential blood flow to the tumors, increasing the T/N ratio (97). 10