吉西他滨致严重肺毒性和全身性毛细血管漏综合征1例

Gemcitabine-induced severe pulmonary toxicity and systemic capillary leak syndrome:a case report and review of the literature

目的:报道1例吉西他滨(GCB)治疗后发生严重肺毒性(SPT)和全身性毛细血管漏综合征(SCLS)的临床及影像学资料,为进一步理解GCB-SPT和GCB-SCLS的发生机制提供参考。方法:收集总结患者的临床资料,讨论化疗中GCB及其他制剂的应用对肺的可能协同毒副作用,并复习GCB-SPT和GCB-SCLS的相关文献。结果:1例72岁男性晚期非小细胞肺癌的患者在应用GCB等化疗后出现非心源性肺水肿和SCIS,SCLS和SIT发生于应用GCB后第5周～9周;其临床特征为亚急性起病,渐进性加重的弥漫性水肿、体重增加、顽固性低蛋白血症、进展迅速的呼吸困难,显著的低氧血症,胸部平片和CT表现为与非心源性肺水肿相一致的间质性肺病变;CT的表现特征包括磨玻璃影、小叶间隔线增厚、网状肺间质浸润阴影、病变呈弥漫性双肺分布、无明显的心影增大及病变为可逆性等;肺功能检查显示,弥散功能中度减低;在明确诊断后,及时停用GCB并加用激素、利尿剂和氧疗等,患者的症状迅速改善并完全缓解,预后良好。分析发病时间顺序和基本病理变化,认为GCB-SCLS可能是GCB-SLT的病理机制之一,G-CSF和IL-11可能是GCB-SCLS及GCB-SLT的促进因素。结论:GCB-SPT和GCB-SCLS相对少见但常严重且可能致命,临床医生应对这种可治性并发症有足够的警觉性,力争早期诊断,及时停用GCB和应用激素、利尿剂和氧疗等,可能会使病情逆转。

Objective:To describe the clinical and imaging features of severe pulmonary toxicity (SPT)and systemic capillary leakage syndrome (SCLS)from gemcitabine (GCB),and to provide the reader with an understanding of the pathologic mechanism of GCB-SPT and GCB-SCLS. Methods: Case data were obtained from patient records. GCB and possible deleterious synergy of the compounds involved in this case were discussed and the literature on GCB-SPT and GCB-SCLS was reviewed. Results: We described the case of a 72-year-old male with advanced non-small-cell lung cancer, who developed noncardiogenic pulmonary edema and SCLS while on treatment with gemcitabine plus granulocyte colony-stimulating factor (G-CSF),interleukin-11 (IL-11)support.SCLS and SPT occurred after 5 weeks ～ 9 weeks of GCB.The clinical features in this case were subacute episode and progressive extensive edema, weight gain,refractory hypoproteinemia,rapid progress dyspnea,marked hypoxemia, and an interstitial infiltrate on chest radiograph and chest CT consistent with noncardiogenic pulmonary edema.CT features of GCB-SPT included ground glass opacity, thickened septal lines, reticular opacities, and distribution of diffuse and bilateral,no evidence of underlying heart disease, infection, or lymphangitic carcinomatosis, and reversible with steroid therapy.Pulmonary function tests was characterized by evidence of middle diffusion dysfunction. Following the early diagnosis,prompt discontinuation of GCB,administration of corticosteroids, diuretics and oxygen therapy,he had rapid and complete resolution of all signs and symptoms of GCB-SPT and GCB-SCLS and survived.There was a direct time correlation between SCLS and GCB. SCLS has been suggested to be the pathogenic mechanism for the GCB-SPT.G-CSF and IL-11 were suggested to be the facilitate agent for the GCB-SPT.Conclusion:GCB-SPT and GCB-SCLS is relatively uncommon but sometimes severe and fatal.Physicians should increase a high index of suspicion of this treatable complication of GCB therapy, early diagnosis and timely intervention with withdrawing GCB, using steroids, diuretics,and oxygen supplementation.