异甘草酸鎂防治胃癌术中氟尿嘧啶缓释植入剂腹腔化疗副反应的临床研究
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摘要
目的：观察异甘草酸镁防治胃癌术中氟尿嘧啶缓释植入剂腹腔化疗所致化学性腹膜炎等副作用的疗效及探讨可能的作用机制,为中药协同治疗肿瘤提供实验及理论依据。
方法：60例确诊并手术的进展期胃癌患者根据入院时间先后分为A组、B组、C组,每组各20例。A组给予术中氟尿嘧啶缓释植入剂腹腔化疗+术后静脉滴注异甘草酸镁一周；B组是仅术中氟尿嘧啶缓释植入剂腹腔化疗；C组不使用氟尿嘧啶缓释植入剂腹腔化疗,术后亦不用异甘草酸镁。观察三组术后腹腔感染和吻合口漏情况、发热及持续时间、消化道反应、肛门排气时间、腹腔引流液量；检测术后第1,3,5天腹腔引流液中蛋白含量、白细胞计数和血清中肿瘤坏死因子α、白介素-1、前列腺素E2含量变化及术后第7,21天肝肾功能、血常规变化。
结果：1、三组患者均未出现腹腔感染和吻合口漏；B组患者比A、C二组发热持续时间延长、消化道不良反应发生率增高、肛门排气时间延长、腹腔引流液增多(P<0.05)；而A、C二组间比较无差异显著性(P>0.05)。2、腹腔引流液蛋白量变化：术后1,3天三组腹腔引流液蛋白量无明显差异(P>0.05)；第5天B组较A、C二组腹腔引流液蛋白明显增多(P<0.01),A组与C组无明显差异(P>0.05)。3、腹腔引流液中白细胞数变化：术后第1天三组引流液白细胞数无明显差异(P>0.05)；第3,5天B组比A、C二组引流液白细胞数明显增多(P<0.05),而A、C组间差异无显著性(P>0.05)。4、血清TNF-α浓度变化：术后第1,3天三组血清TNF-α无差异显著性(P>0.05)；第5天B组较C及A组血清TNF-α明显升高(P<0.05),A和C组间无差异显著性(P>0.05)。5、血清IL-l浓度变化：术后第1,3天三组血清IL-1差异无显著性(P>0.05)；第5天A、B二组较C组IL-1明显升高(P<0.01),而A、B二组无明显差异(P>0.05)。6、血清PGE2浓度变化：术后第1天三组血清PGE2无明显差异(P>0.05)；第3,5天B组血清PGE2比A、C二组明显升高(P<0.01),A、C组间差异无显著性(P>0.05)。7、对肝肾功能、血白细胞影响：术后第7,21天三组间差异无显著性(P>0.05)。
结论：1、胃癌术中氟尿嘧啶缓释植入剂腹腔化疗所致的副反应主要是化学刺激性腹膜炎；2、异甘草酸镁能减轻氟尿嘧啶缓释植入剂腹腔化疗所致化学性腹膜炎等副反应；3、异甘草酸镁可通过抑制炎症介质TNF-α和PGE2的表达和释放来发挥抗炎作用。
Objective:To observe therapeutic effect and explore possible mechanism of magnesium isoglycyrrhizinate on preventing chemical peritonitis and other side effects caused by intraperitoneal chemotherapy with sustained-release fluorouracil for implant in gastric cancer surgery, provide experimental and theoretical basis on collaborative treating of tumor with traditional Chinese medicine.
Methods:60 cases operated and diagnosed with advanced gastric cancer were divided into A, B and C groups according to chronological admission,20 patients in each group. A group is given intraoperative intraperitoneal chemotherapy with sustained-release fluorouracil for implant and dripped magnesium isoglycyrrhizinate about a week after surgery.For B group, only is received intraoperative intraperitoneal chemotherapy with sustained-release fluorouracil for implant.In C group, neither is adopted intraperitoneal chemotherapy with sustained-release fluorouracil for implant and not dripped magnesium isoglycyrrhizinate after surgery. Observe three groups of celiac infection and anastomotic leakage, postoperative fever and duration, gastrointestinal reaction,the time of anus exhaust,quantity of celiac drainage fluid;test the change in content of protein and the count of white blood cell in peritoneal drainage fluid and the content of tumor necrosis factorα、interleukin-1、prostaglandin E2 in serum in 1,3 and 5 days after operation and the changes of liver and kidney function,routine blood in 7 and 21 days after surgery.
Results:1. Three groups of patients all do not appear celiac infection and anastomotic leakage;the patients in B group on duration of fever, the incidence of gastrointestinal reactions, time of anus exhaust and peritoneal fluid drainage are significantly prolonged or increased than these in A and C groups (P<0.05), but there is no significant difference in A and C groups (P>0.05).2.The changes of content on protein in the peritoneal fluid drainage:there are no obvious difference in content of protein in the peritoneal fluid drainage in land 3 days after surgery among three groups(P>0.05).In 5 day, the content of protein in the peritoneal fluid drainage in group B are significantly increased than it in A and C groups (P<0.01),but A and C groups have no obvious difference (P>0.05).3.The changes of count on White blood cell in the peritoneal fluiddrainage:In 1 days after surgery among three groups, there are no obvious differenceabout the count of White blood cell in the peritoneal fluid drainage (P>0.05). In 3 and 5 days, the count of White blood cell in group B are significantly increased than it in A and C groups (P<0.05), but have no obvious difference in A and C groups (P>0.05).4.The changes of content on TNF-a in serum: there are no significant difference about TNF-a in serum in 1 and 3 days after surgery among three groups(P>0.05),but in 5 days, the serum concentrations of TNF-a in group B are obvious increased than it in A and C groups(P<0.05), but there are no statistically significant difference in A and C groups(P>0.05).5.The changes of content on IL-1 in serum:there are no significant difference about IL-1 in serum in land 3 days after surgery among three groups(P>0.05).In 5 days, compared with the C group,the serum content of IL-1 in A and B groups are significantly increased (P<0.01), but there have no obvious difference in A and B groups (P>0.05).6.The changes of content on PGE2 in serum:there are no significant difference about PGE2 in serum in 1 days after surgery among three groups(P>0.05). In 3 and 5 days after surgery, the serum concentrations of PGE2 in group B are obvious increased than it in A and C groups (P<0.01), but there have no obvious difference in A and C groups (P>0.05).7.It have no obvious difference about changes of liver and kidney function and routine blood in 7and 21 days after operation among three groups (P>0.05).
Conclusions:1.The main side effects about intraperitoneal chemotherapy with sustained- release fluorouracil for implant in gastric cancer surgery are chemical irritant peritonitis.2. Magnesium isoglycyrrhizinate can reduce chemical peritonitis and other side effects caused by intraperitoneal chemotherapy with sustained-release fluorouracil forimplant.3.The mechanism of anti-inflammatory effects about magnesium isoglycyrrhizinate may inhibit the inflammatory mediators TNF-a and PGE2 express and release.
方法：60例确诊并手术的进展期胃癌患者根据入院时间先后分为A组、B组、C组,每组各20例。A组给予术中氟尿嘧啶缓释植入剂腹腔化疗+术后静脉滴注异甘草酸镁一周；B组是仅术中氟尿嘧啶缓释植入剂腹腔化疗；C组不使用氟尿嘧啶缓释植入剂腹腔化疗,术后亦不用异甘草酸镁。观察三组术后腹腔感染和吻合口漏情况、发热及持续时间、消化道反应、肛门排气时间、腹腔引流液量；检测术后第1,3,5天腹腔引流液中蛋白含量、白细胞计数和血清中肿瘤坏死因子α、白介素-1、前列腺素E2含量变化及术后第7,21天肝肾功能、血常规变化。
结果：1、三组患者均未出现腹腔感染和吻合口漏；B组患者比A、C二组发热持续时间延长、消化道不良反应发生率增高、肛门排气时间延长、腹腔引流液增多(P<0.05)；而A、C二组间比较无差异显著性(P>0.05)。2、腹腔引流液蛋白量变化：术后1,3天三组腹腔引流液蛋白量无明显差异(P>0.05)；第5天B组较A、C二组腹腔引流液蛋白明显增多(P<0.01),A组与C组无明显差异(P>0.05)。3、腹腔引流液中白细胞数变化：术后第1天三组引流液白细胞数无明显差异(P>0.05)；第3,5天B组比A、C二组引流液白细胞数明显增多(P<0.05),而A、C组间差异无显著性(P>0.05)。4、血清TNF-α浓度变化：术后第1,3天三组血清TNF-α无差异显著性(P>0.05)；第5天B组较C及A组血清TNF-α明显升高(P<0.05),A和C组间无差异显著性(P>0.05)。5、血清IL-l浓度变化：术后第1,3天三组血清IL-1差异无显著性(P>0.05)；第5天A、B二组较C组IL-1明显升高(P<0.01),而A、B二组无明显差异(P>0.05)。6、血清PGE2浓度变化：术后第1天三组血清PGE2无明显差异(P>0.05)；第3,5天B组血清PGE2比A、C二组明显升高(P<0.01),A、C组间差异无显著性(P>0.05)。7、对肝肾功能、血白细胞影响：术后第7,21天三组间差异无显著性(P>0.05)。
结论：1、胃癌术中氟尿嘧啶缓释植入剂腹腔化疗所致的副反应主要是化学刺激性腹膜炎；2、异甘草酸镁能减轻氟尿嘧啶缓释植入剂腹腔化疗所致化学性腹膜炎等副反应；3、异甘草酸镁可通过抑制炎症介质TNF-α和PGE2的表达和释放来发挥抗炎作用。
Objective:To observe therapeutic effect and explore possible mechanism of magnesium isoglycyrrhizinate on preventing chemical peritonitis and other side effects caused by intraperitoneal chemotherapy with sustained-release fluorouracil for implant in gastric cancer surgery, provide experimental and theoretical basis on collaborative treating of tumor with traditional Chinese medicine.
Methods:60 cases operated and diagnosed with advanced gastric cancer were divided into A, B and C groups according to chronological admission,20 patients in each group. A group is given intraoperative intraperitoneal chemotherapy with sustained-release fluorouracil for implant and dripped magnesium isoglycyrrhizinate about a week after surgery.For B group, only is received intraoperative intraperitoneal chemotherapy with sustained-release fluorouracil for implant.In C group, neither is adopted intraperitoneal chemotherapy with sustained-release fluorouracil for implant and not dripped magnesium isoglycyrrhizinate after surgery. Observe three groups of celiac infection and anastomotic leakage, postoperative fever and duration, gastrointestinal reaction,the time of anus exhaust,quantity of celiac drainage fluid;test the change in content of protein and the count of white blood cell in peritoneal drainage fluid and the content of tumor necrosis factorα、interleukin-1、prostaglandin E2 in serum in 1,3 and 5 days after operation and the changes of liver and kidney function,routine blood in 7 and 21 days after surgery.
Results:1. Three groups of patients all do not appear celiac infection and anastomotic leakage;the patients in B group on duration of fever, the incidence of gastrointestinal reactions, time of anus exhaust and peritoneal fluid drainage are significantly prolonged or increased than these in A and C groups (P<0.05), but there is no significant difference in A and C groups (P>0.05).2.The changes of content on protein in the peritoneal fluid drainage:there are no obvious difference in content of protein in the peritoneal fluid drainage in land 3 days after surgery among three groups(P>0.05).In 5 day, the content of protein in the peritoneal fluid drainage in group B are significantly increased than it in A and C groups (P<0.01),but A and C groups have no obvious difference (P>0.05).3.The changes of count on White blood cell in the peritoneal fluiddrainage:In 1 days after surgery among three groups, there are no obvious differenceabout the count of White blood cell in the peritoneal fluid drainage (P>0.05). In 3 and 5 days, the count of White blood cell in group B are significantly increased than it in A and C groups (P<0.05), but have no obvious difference in A and C groups (P>0.05).4.The changes of content on TNF-a in serum: there are no significant difference about TNF-a in serum in 1 and 3 days after surgery among three groups(P>0.05),but in 5 days, the serum concentrations of TNF-a in group B are obvious increased than it in A and C groups(P<0.05), but there are no statistically significant difference in A and C groups(P>0.05).5.The changes of content on IL-1 in serum:there are no significant difference about IL-1 in serum in land 3 days after surgery among three groups(P>0.05).In 5 days, compared with the C group,the serum content of IL-1 in A and B groups are significantly increased (P<0.01), but there have no obvious difference in A and B groups (P>0.05).6.The changes of content on PGE2 in serum:there are no significant difference about PGE2 in serum in 1 days after surgery among three groups(P>0.05). In 3 and 5 days after surgery, the serum concentrations of PGE2 in group B are obvious increased than it in A and C groups (P<0.01), but there have no obvious difference in A and C groups (P>0.05).7.It have no obvious difference about changes of liver and kidney function and routine blood in 7and 21 days after operation among three groups (P>0.05).
Conclusions:1.The main side effects about intraperitoneal chemotherapy with sustained- release fluorouracil for implant in gastric cancer surgery are chemical irritant peritonitis.2. Magnesium isoglycyrrhizinate can reduce chemical peritonitis and other side effects caused by intraperitoneal chemotherapy with sustained-release fluorouracil forimplant.3.The mechanism of anti-inflammatory effects about magnesium isoglycyrrhizinate may inhibit the inflammatory mediators TNF-a and PGE2 express and release.
引文
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