van Ijken M G, de Bruijn E A, de Boeck G, ten Hagen T L, van der Sijp J R, Eggermont A M
Department of Surgical Oncology, University Hospital Rotterdam-Daniël den Hoed Cancer Center, Rotterdam, The Netherlands.
Ann Surg. 1998 Dec;228(6):763-70. doi: 10.1097/00000658-199812000-00007.
To validate the methodology of isolated hypoxic hepatic perfusion (IHHP) using balloon catheter techniques and to gain insight into the distribution of tumor necrosis factor-alpha (TNF), melphalan, and mitomycin C (MMC) through the regional and systemic blood compartments when applying these techniques.
There is no standard treatment for unresectable liver tumors. Clinical results of isolated limb perfusion with high-dose TNF and melphalan for the treatment of melanoma and sarcoma have been promising, and attempts have been made to extrapolate this success to the isolated liver perfusion setting. The magnitude and toxicity of the surgical procedure, however, have limited clinical applicability.
Pigs underwent IHHP with TNF, melphalan, and MMC using balloon catheters or served as controls, receiving equivalent dosages of these agents intravenously. After a 20-minute perfusion, a washout procedure was performed for 10 minutes, after which isolation was terminated. Throughout the procedure and afterward, blood samples were obtained from the hepatic and systemic blood compartments and concentrations of perfused agents were determined.
During perfusion, locoregional plasma drug concentrations were 20- to 40-fold higher than systemic concentrations. Compared with systemic concentrations after intravenous administration, regional concentrations during IHHP were up to 10-fold higher. Regional MMC and melphalan levels steadily declined during perfusion, indicating rapid uptake by the liver tissue; minimal systemic concentrations indicated virtually no leakage to the systemic blood compartment. During isolation, concentrations of TNF in the perfusate declined only slightly, indicating limited uptake by the liver tissue; no leakage of TNF to the systemic circulation was observed. After termination of isolation, systemic TNF levels showed only a minor transient elevation, indicating that the washout procedure at the end of the perfusions was fully effective.
Complete isolation of the hepatic vascular bed can be accomplished when performing IHHP using this balloon catheter technique. Thus, as in extremities, an ideal leakage-free perfusion of the liver can now be performed, and repeated, without major surgery. The effective washout allows the addition of TNF in this setting.
验证使用球囊导管技术进行孤立性缺氧肝灌注（IHHP）的方法，并在应用这些技术时深入了解肿瘤坏死因子-α（TNF）、美法仑和丝裂霉素C（MMC）在局部和全身血腔中的分布情况。
对于不可切除的肝肿瘤，尚无标准治疗方法。高剂量TNF和美法仑用于孤立肢体灌注治疗黑色素瘤和肉瘤的临床结果很有前景，并且已尝试将这一成功经验推广到孤立肝灌注的情况。然而，手术操作的规模和毒性限制了其临床应用。
使用球囊导管对猪进行TNF、美法仑和MMC的IHHP，或作为对照，静脉内给予这些药物的等效剂量。灌注20分钟后，进行10分钟的冲洗程序，之后终止隔离。在整个过程及之后，从肝血腔和全身血腔采集血样，并测定灌注药物的浓度。
灌注期间，局部血浆药物浓度比全身浓度高20至40倍。与静脉给药后的全身浓度相比，IHHP期间的局部浓度高出多达10倍。灌注期间局部MMC和美法仑水平稳步下降，表明肝组织快速摄取；全身浓度极低表明几乎没有渗漏到全身血腔。隔离期间，灌注液中TNF的浓度仅略有下降，表明肝组织摄取有限；未观察到TNF渗漏到体循环。隔离终止后，全身TNF水平仅出现轻微短暂升高，表明灌注结束时的冲洗程序完全有效。
使用这种球囊导管技术进行IHHP时，可以实现肝血管床的完全隔离。因此，与四肢情况一样，现在可以在不进行大手术的情况下，对肝脏进行理想的无渗漏灌注，并可重复进行。有效的冲洗使得在这种情况下可以添加TNF。
