盆腔腹膜外化疗法重复给药的临床研究

Chemotherapy Repeated Injection Via Pelvic Retroperitoneal Cannulation

目的：探讨盆腔腹膜外化疗法重复给药用于临床治疗肿瘤淋巴系转移的可行性。方法：选２５只家犬和２４例妇科恶性肿瘤患者，经盆腔腹膜外间隙穿刺插管注入５－氟尿嘧啶（５－ＦＵ）、噻替派或氨甲喋呤。采用高效液相色谱和病理检查的方法，观察药物分布范围内淋巴结及其周围组织的药物浓度和病理改变。结果：动物实验结果表明，重复给药对给药区血管、输尿管及其它正常组织未见毒性作用；淋巴结内５－ＦＵ浓度是周围结缔组织的７～９倍，重复给药组淋巴结内浓度是单次给药组的１１～１３倍。临床研究结果表明：（１）药物分布范围包括了髂内外、闭孔、腹股沟深和大部分髂总淋巴结；（２）重复给药组盆腔和腹主动脉旁淋巴结内５－ＦＵ浓度分别是单次给药组的２０～７３倍和２７～１１０倍，淋巴结内浓度是周围结缔组织的１１～２０倍；（３）光镜下可见注药侧淋巴结内转移癌细胞有明显的变性坏死，而对照侧未见改变；（４）本组患者未发生并发症及明显的全身毒副作用。结论：盆腔腹膜外化疗法重复给药是安全可行的，并可能是妇科恶性肿瘤淋巴系转移的有效治疗方法之一。

Objective: To investigate the feasibility of chemotherapy for lymphatic metastases of gynecologic cancer by repeated injection via pelvic retroperitoneal connulation. Methods: 5 fluorouracil (5 FU), thiotepa, methofrexate were repeatedly injected into the pelvic retroperitoneal space of 25 dogs and 24 patients respectively via a cannulation. Microscope and high performance liquid chromatography were used to observe the drug concentration of 5 FU and pathologic changes of the involved tissues. Results: Animal experiment showed no toxicity to vessels, ureter and the nomal tissues involved; nodal 5 FU concentration of repeated injection side was 7 to 9 times of that on the peripheral connective tissue ( P <0.05). Clinical study revealed: (1) the external iliac, hypogastric, obturator, deep inguinal and most of the commen iliac lymph nodes were submerged in the 5 FU solution; (2) pelvic and periaortic nodal 5 FU concentrations of repeated injection side were 20 to 73 and 27 to 110 times of that on single injection side respectively; nodal 5 FU concentration was 11 to 20 times of that on the peripheral connective tissue; (3) metastatic cancer cells of nodal in the study group showed obvious degeneration and necrosis while no changes in the control; (4) no severe complications or adverse effects were observed. Conclusion: Repeated injection via pelvic retroperitoneal cannulation was feasible and probably more effective for the treatment of lymphatic metastases of gynecologic cancer.