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目的观察胃癌根治术中区域动脉灌注化疗后的药物分布特征、术后组织病理变化及临床毒副反应。方法将我科自2007年9月至2008年11月期间符合区域动脉灌注化疗纳入适应证的60例患者随机平均分为治疗组和对照组,治疗组于胃癌根治术中经肿瘤的主要供血动脉灌注含2 ml亚甲蓝、5-FU(1 000 mg/m2)和MMC(10 mg/m2)的灌注液100 ml;对照组不进行区域动脉灌注化疗。观察术中亚甲蓝的分布特征,术后观察肿瘤组织病理学改变及临床毒副反应。结果治疗组肿瘤区域立即显色,此后染色逐渐变淡,但全手术过程中肿瘤区域仍可见染色。术后光镜观察见癌细胞出现轻度细胞核固缩或肿胀,细胞浆凝固,细胞间质轻度水肿,炎性细胞浸润,部分病例可见轻度血管炎表现。透射电镜见癌细胞核固缩或肿胀,核异染色质凝集,核周间隙扩大,胞质线粒体肿胀,内质网扩张,高尔基复合体扩张。治疗组术后第1天AST较术前明显增高(P<0.01),但术后第3天即恢复正常(P>0.05);2组患者术后肝功能其余指标(ALT、ALP、GGT、LDH)、肾功能指标(尿素和肌酐)、毒副反应(胃肠道反应和骨髓抑制)及床旁心电图差异均无统计学意义(P>0.05);2组均未出现吻合口漏。结论胃癌根治术中区域动脉灌注化疗后使胃癌原发灶在全手术过程暴露于化疗药物中,可降低癌细胞的活性;临床观察其毒副反应小,可作为外科手术的重要补充手段来预防术中医源性扩散和术后的复发。
Objective To observe the characteristics of drug distribution, histopathological changes and clinical toxicities after regional arterial infusion chemotherapy in radical operation of gastric cancer. Methods Sixty patients in our department who were eligible for regional arterial infusion chemotherapy were randomly divided into treatment group and control group from September 2007 to November 2008. The patients in the treatment group underwent primary radical resection of gastric cancer 100 ml of perfusate containing 2 ml of methylene blue, 5-FU (1 000 mg / m 2) and MMC (10 mg / m 2) was infused; no regional arterial infusion chemotherapy was administered in the control group. The distribution of methylene blue in operation was observed. The histopathological changes and clinical toxicity were observed after operation. Results In the treatment group, the tumor area immediately developed color, and the staining gradually fades afterwards. However, the staining of the tumor area can still be seen during the whole operation. Postoperative light microscopy showed cancer cells showed mild nuclear pyknosis or swelling, cytoplasm coagulation, interstitial mild edema, inflammatory cell infiltration, in some cases showed mild vasculitis. Transmission electron microscopy showed nuclear condensation or swelling of the cancer cells, nuclear heterochromatin agglutination, perinuclear space expansion, cytoplasmic mitochondria swelling, endoplasmic reticulum dilation, expansion of the Golgi complex. The AST in the treatment group was significantly higher than that before operation (P <0.01), but returned to normal on the third day after operation (P> 0.05). The remaining indexes of liver function (ALT, ALP, GGT, LDH), renal function (urea and creatinine), toxicity (gastrointestinal reaction and myelosuppression) and bedside ECG (P> 0.05). There was no anastomotic leakage in both groups. Conclusions Regional arterial chemoembolization during radical operation of gastric cancer exposes the primary tumor of gastric cancer to chemotherapeutic drugs during the whole operation, which can reduce the activity of cancer cells. The clinical observation of its small toxic and side reaction can be used as an important supplementary means of surgery to prevent Intraoperative iatrogenic diffusion and postoperative recurrence.