食管癌术中淋巴结化疗的临床研究

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目的淋巴结转移是影响食管癌患者预后的主要因素。淋巴结化疗(lymph node chemotherapy,LNC)采用吸附了化疗药物的载体可被淋巴结中巨噬细胞吞噬的原理实现淋巴结的“靶向化疗”。本研究探讨LNC在食管癌术中的运用价值,筛选LNC中的较优药物,并与同期静脉化疗对比。方法选取2013-01-21-2013-10-23四川大学华西医院胸外科接受食管癌治疗的患者92例,采取单中心前瞻性半随机单盲对照研究。其中紫杉醇-纳米炭淋巴结化疗组(LNC by paclitaxel-carbon nanoparticles,LNP)、氟尿嘧啶-纳米炭淋巴结化疗组(LNC by fluorouracil-carbon nanoparticles,LNF)各41例,按相应药物接受术中LNC;氟尿嘧啶静脉化疗组(venous chemotherapy by fluorouracil,VF)10例,接受术中氟尿嘧啶静脉化疗。光镜下观察注射部位及淋巴结内药物分布,比较各组淋巴结、血清相应药物浓度。结果光镜下吸附了化疗药物的纳米炭未引起局部组织炎性细胞浸润及坏死,并可聚集于淋巴结皮质。LNP组淋巴结中紫杉醇药物浓度为2.16(3.25),高于血清浓度0.00(0.00),Z=-5.579,P<0.01。LNF组淋巴结中氟尿嘧啶药物浓度为0.44(1.07),也高于血清浓度0.00(0.31),Z=-3.069,P<0.01。而VF组淋巴结药物浓度0.11(0.26)与血药浓度0.00(0.15)的差异无统计学意义,Z=-0.135,P=0.893。LNF组淋巴结内药物浓度0.44(1.07)比VF组0.11(0.26)高,H=94.500,P<0.01。LNP组淋巴结内药物浓度2.16(3.25)高于LNF组0.44(1.07),H=351.000,P<0.01,血清药物浓度0.00(0.00)则低于LNF组0.00(0.31),H=577.000,P<0.01。结论在食管癌术中,LNC可安全、有效地使化疗药物靶向进入并停留于淋巴结,在淋巴结转移疗效上可能优于同期静脉化疗。实施LNC时,优选对载体亲和力高的药物。 The purpose of lymph node metastasis is the main factor affecting the prognosis of esophageal cancer patients. Lymph node chemotherapy (lymph node chemotherapy, lymph node chemotherapy, LNC) using the principle of adsorption of chemotherapeutic drugs can be phagocytosed by macrophages in lymph nodes. This study explored the value of LNC in esophageal cancer surgery, screening of superior drugs in LNC, and compared with the same period of intravenous chemotherapy. Methods Totally 92 patients undergoing esophageal cancer treatment in the Department of Thoracic Surgery, West China Hospital, Sichuan University were enrolled in this study. A single-center prospective randomized single-blind controlled study was performed. 41 cases of LNC by paclitaxel-carbon nanoparticles (LNP) and 5 cases of LNC by fluorouracil-carbon nanoparticles (LNF) were treated with LNC by the corresponding drugs, 5-fluorouracil Ten patients in the chemotherapy group received fluorouracil intravenous chemotherapy. The distribution of drug in injection site and lymph node was observed under light microscope. The concentration of corresponding drug in lymph nodes and serum in each group was compared. Results Nanoparticles adsorbed with chemotherapeutic agents under light microscope did not cause infiltration and necrosis of inflammatory cells in local tissues and could accumulate in the lymph node cortex. The drug concentration of paclitaxel in LNP group was 2.16 (3.25), higher than the serum concentration 0.00 (0.00), Z = -5.579, P <0.01. The concentration of fluorouracil in LNF group was 0.44 (1.07), higher than 0.00 (0.31) in serum and Z = -3.069, P <0.01. However, there was no significant difference in the drug concentration of lymph node between 0.11 (0.26) and 0.00 (0.15) in VF group, Z = -0.135, P = 0.893. The drug concentration in LNF group was 0.44 (1.07) higher than that in VF group (0.26), H = 94.500, P <0.01. The drug concentration in LNP group was 2.16 (3.25) higher than that in LNF group (0.44 (1.07), H = 351.000, P <0.01), and the serum concentration was 0.00 (0.00) 0.01. Conclusions In esophagectomy, LNC can safely and effectively target chemotherapeutic drugs to enter and remain in the lymph nodes, which may be superior to the concurrent intravenous chemotherapy in lymph node metastasis. In the case of LNC, a drug having a high affinity for a carrier is preferable.
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