Stam T C, Swaak A J, de Vries M R, ten Hagen T L, Eggermont A M
Department of Surgical Oncology, University Hospital Rotterdam-Dr. Daniel den Hoed Cancer Center, The Netherlands.
Ann Surg Oncol. 2000 May;7(4):268-75. doi: 10.1007/s10434-000-0268-6.
Since the introduction of high-dose tumor necrosis factor-alpha (TNFalpha) in the setting of isolated limb perfusion (ILP) in the clinic, prevention of leakage to the body of the patient is monitored with great precision for fear of TNF-mediated toxicity. That we observed remarkably little toxicity in patients with and without leakage prompted us to determine patterns of cytokines and acute phase proteins in patients with high leakage and in patients without any leakage.
TNFalpha, interleukin (IL)-6, IL-8, C-reactive protein, and secretory (s)-phospholipase A2 were measured at several time points during and after (until 7 days) ILP in 10 patients with a leakage to the systemic circulation varying in percentage from 12% to 65%. As a control, the same measurements, both in peripheral blood and in perfusate, were performed in nine patients without systemic leakage.
In patients with systemic leakage, levels of TNFalpha increased during ILP, reaching values to 277 ng/ml. IL-6 and IL-8 peaked 3 hours after ILP with values significantly higher compared with patients without systemic leakage. C-reactive protein and s-phospholipase A2 peaked at day 1 in both patient groups, s-phospholipase A2 with significant higher levels and C-reactive protein, in contrast, with lower levels in the leakage patients.
High leakage of TNFalpha to the systemic circulation, caused by a complicated ILP, led to 10-fold to more than 100-fold increased levels of TNFalpha, IL-6, and IL-8 in comparison with patients without leakage. The increase of the acute phase proteins was limited. Even when high leakage occurs, this procedure should not lead to fatal complications. The most prominent clinical toxicity was hypotension (grade III in four patients), which was easily corrected. No pulmonary or renal toxicity was observed in any patient. It is our experience that, even in the rare event of significant leakage during a TNFa-based ILP, postoperative toxicity is usually mild and can be easily managed by the use of fluid and, in some cases, vasopressors.
自从高剂量肿瘤坏死因子-α（TNFα）在临床孤立肢体灌注（ILP）中应用以来，由于担心TNF介导的毒性，对防止其漏入患者体内进行了精确监测。我们观察到，无论有无渗漏，患者的毒性都非常小，这促使我们确定高渗漏患者和无渗漏患者体内细胞因子和急性期蛋白的模式。
在10例全身循环渗漏率从12%到65%不等的患者进行ILP期间及之后（直至7天）的几个时间点，测量TNFα、白细胞介素（IL）-6、IL-8、C反应蛋白和分泌型（s）-磷脂酶A2。作为对照，对9例无全身渗漏的患者进行外周血和灌注液的相同测量。
在全身渗漏的患者中，ILP期间TNFα水平升高，达到277 ng/ml。IL-6和IL-8在ILP后3小时达到峰值，其值显著高于无全身渗漏的患者。两组患者的C反应蛋白和s-磷脂酶A2均在第1天达到峰值，s-磷脂酶A2水平显著更高，而C反应蛋白在渗漏患者中水平较低。
复杂的ILP导致TNFα大量漏入全身循环，与无渗漏患者相比，TNFα、IL-6和IL-8水平升高了10倍至100倍以上。急性期蛋白的增加有限。即使发生高渗漏，该操作也不应导致致命并发症。最突出的临床毒性是低血压（4例患者为III级），很容易纠正。所有患者均未观察到肺部或肾脏毒性。我们的经验是，即使在基于TNFα的ILP过程中罕见地发生大量渗漏，术后毒性通常也很轻微，通过补液，在某些情况下使用血管升压药即可轻松处理。
