Verhoef Cornelis, de Wilt Johannes H W, Brunstein Flavia, Marinelli Andreas W K S, van Etten Boudewijn, Vermaas Maarten, Guetens Gunther, de Boeck Gert, de Bruijn Ernst A, Eggermont Alexander M M
Department of Surgical Oncology, Erasmus University Medical Centre-Daniel den Hoed Cancer Centre, PO Box 5201, 3008 AE, Rotterdam, The Netherlands.
Ann Surg Oncol. 2008 May;15(5):1367-74. doi: 10.1245/s10434-007-9714-z. Epub 2008 Feb 1.
Isolated hepatic perfusion with high-dose chemotherapy is a treatment option for patients with irresectable metastases confined to the liver. Prolonged local control and impact on survival have been claimed. Major drawbacks are magnitude and costs of the procedure. We developed an isolated hypoxic hepatic perfusion (IHHP) with retrograde outflow without the need for a heart-lung machine.
Twenty-four consecutive patients with irresectable metastases of various origins were treated. IHHP inflow was via the hepatic artery, outflow via the portal vein with occlusion of the retrohepatic caval vein. Radiolabeled albumine was used for leakage monitoring. Melphalan was used at 1-2 mg/kg. A 25-minute perfusion period was followed by a complete washout. Local and systemic melphalan concentrations were determined.
Compared with oxygenated classical IHP, the IHPP procedure reduced operation time from >8 h to 4 hours, blood loss from >4000 to 900 cc and saved material and personnel costs. Leakage was 0% with negligible systemic toxicity and 0% perioperative mortality. Tumor response: complete response (CR) in 4%, partial response (PR) in 58%, and stable disease (SD) in 13%. Median time to progression was 9 months (2-24 months); pharmacokinetics demonstrated intrahepatic melphalan concentrations more than 9 fold higher than postperfusion systemic concentrations.
IHPP is a relatively simple procedure with reduced costs, reduced blood loss, no mortality, limited toxicity, and response rates comparable to classic IHP. The median duration of 9 months of tumor control should be improved. Hereto, vasoactive drugs, will be explored in further studies.
高剂量化疗的孤立性肝灌注是局限于肝脏的不可切除转移瘤患者的一种治疗选择。有人声称其可实现长期局部控制并影响生存率。主要缺点是该手术的规模和成本。我们开发了一种无需体外循环机的逆行流出的孤立性低氧肝灌注（IHHP）。
连续治疗了24例各种来源的不可切除转移瘤患者。IHHP的血流通过肝动脉进入，通过门静脉流出，同时阻断肝后腔静脉。使用放射性标记的白蛋白进行渗漏监测。美法仑的使用剂量为1 - 2mg/kg。灌注25分钟后进行彻底冲洗。测定局部和全身美法仑浓度。
与充氧的经典IHP相比，IHPP手术将手术时间从>8小时缩短至4小时，失血量从>4000cc减少至900cc，并节省了材料和人员成本。渗漏率为0%，全身毒性可忽略不计，围手术期死亡率为0%。肿瘤反应：完全缓解（CR）占4%，部分缓解（PR）占58%，疾病稳定（SD）占13%。中位进展时间为9个月（2 - 24个月）；药代动力学显示肝内美法仑浓度比灌注后全身浓度高9倍以上。
IHPP是一种相对简单的手术，成本降低，失血量减少，无死亡率，毒性有限，反应率与经典IHP相当。肿瘤控制的中位持续时间9个月有待提高。为此，将在进一步研究中探索血管活性药物。
