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肠道屏障功能对消化道肿瘤化学治疗后不良反应及营养状况的影响
余嘉文1,姚文娟1,朱和玲1,程进1,江昊1,刘斌2,刘道利2*
0
(1. 安徽医科大学附属安庆第一人民医院, 安徽省安庆市第一人民医院肿瘤科, 安庆 246052;
2. 安徽医科大学附属安庆第一人民医院, 安徽省安庆市第一人民医院胃肠外科, 安庆 246052
*通信作者)
摘要:
目的 评价肠道屏障功能指标二胺氧化酶(DAO)、D-乳酸、内毒素对消化道肿瘤化学治疗(以下简称化疗)后常见不良反应发生率和营养状况变化的影响,确定肠道屏障功能指标对于化疗后不良反应和营养状态恶化的最佳预测值。方法 收集2019年9月至2022年5月安徽医科大学附属安庆第一人民医院收治的77例消化道肿瘤患者的化疗前血清DAO、D-乳酸和内毒素,以及化疗前、后患者主观整体营养评估量表(PG-SGA)评分等临床资料。通过比较不同临床特征患者的DAO、D-乳酸和内毒素水平探究肠道屏障功能对化疗后不良反应和营养状态的影响。采用二元logistic回归分析筛选化疗后不良反应和营养状态恶化的影响因素,使用ROC曲线和约登指数确定DAO、D-乳酸和内毒素对化疗后不良反应和营养状态恶化的最佳预测值。结果 骨髓抑制的发生不受DAO、D-乳酸和内毒素水平影响。化疗后呕吐、腹泻和营养状态恶化患者的化疗前DAO和D-乳酸水平较无呕吐、无腹泻和营养状态未恶化的患者更高(P均<0.05)。化疗后腹泻和转氨酶升高患者的化疗前内毒素水平较无腹泻和转氨酶未升高的患者更高(P均<0.001)。回归分析显示化疗前DAO、D-乳酸和3个月内行胃肠手术与化疗后呕吐相关(P均<0.05),D-乳酸是化疗后腹泻的独立影响因素(P=0.001),后程化疗和D-乳酸增高是化疗后营养状态恶化的影响因素(P均<0.05)。内毒素对于化疗后转氨酶升高的最佳预测值为17.36 U/L(AUC=0.850,P<0.001),DAO和D-乳酸对化疗后呕吐的最佳预测值分别为10.47 U/L(AUC=0.727,P=0.001)和18.55 mg/L(AUC=0.708,P=0.003),D-乳酸对化疗后腹泻的最佳预测值为17.63 mg/L(AUC=0.920,P<0.001),D-乳酸对于化疗后营养状态恶化的最佳预测值为12.77 mg/L(AUC=0.684,P=0.006)。结论 肠道屏障功能指标DAO、D-乳酸和内毒素对于化疗后呕吐、腹泻、转氨酶升高和营养状态恶化均有预测作用。
关键词:  胃肠肿瘤  肠道屏障  化学疗法  药物相关性副作用和不良反应  营养状况
DOI:10.16781/j.CN31-2187/R.20220319
投稿时间:2022-04-21修订日期:2022-09-02
基金项目:安徽医科大学校基金资助项目(2021xkj089),皖南医学院教学医院科研专项(JXYY202285).
Effects of intestinal barrier function on adverse reactions and nutritional status of patients with gastrointestinal tumor after chemotherapy
YU Jia-wen1,YAO Wen-juan1,ZHU He-ling1,CHENG Jin1,JIANG Hao1,LIU Bin2,LIU Dao-li2*
(1. Department of Oncology, Anqing First People's Hospital of Anhui Medical University & Anqing First People's Hospital of Anhui Province, Anqing 246052, Anhui, China;
2. Department of Gastrointestinal Surgery, Anqing First People's Hospital of Anhui Medical University & Anqing First People's Hospital of Anhui Province, Anqing 246052, Anhui, China
*Corresponding author)
Abstract:
Objective To evaluate the effects of intestinal barrier function indicators (diamine oxidase [DAO], D-lactic acid [DLA], and endotoxin [ET]) on common adverse reactions and nutritional status of patients with gastrointestinal tumor after chemotherapy, and to determine the best predictive values of intestinal barrier function indicators for them. Methods A total of 77 patients with gastrointestinal tumors who were admitted to Anqing First People’s Hospital of Anhui Medical University from Sep. 2019 to May 2022 were enrolled. DAO, DLA and ET of patients before chemotherapy and pre- and post-chemotherapy patient generated subjective global assessment (PG-SGA) scores were collected. The effects of intestinal barrier function on adverse reactions and nutritional status after chemotherapy were analyzed by comparing the levels of DAO, DLA and ET in patients with different clinical characteristics. The influencing factors of adverse reactions and nutritional deterioration were screened using binary logistic regression analysis. The best predictive values of DAO, DLA and ET for adverse reactions and nutritional deterioration were determined using receiver operating characteristic curve and Youden index. Results The occurrence of myelosuppression was not affected by the levels of DAO, DLA and ET. Patients with vomiting, diarrhea or nutritional deterioration after chemotherapy had significantly higher DAO and DLA before chemotherapy (all P<0.05). Patients with diarrhea or elevated transaminase after chemotherapy had significantly higher ET before chemotherapy (both P<0.001). Regression analysis showed that DAO and DLA before chemotherapy and gastrointestinal surgery within 3 months were related to the occurrence of vomiting (all P<0.05). DLA is an independent influence factor of diarrhea after chemotherapy (P=0.001). Late cycle chemotherapy and elevated DLA were the influencing factors of nutritional deterioration after chemotherapy (both P<0.05). The best predictive value of ET for transaminase elevation after chemotherapy was 17.36 U/L (area under curve [AUC] =0.850, P<0.001). The best predictive values of DAO and DLA for vomiting were 10.47 U/L (AUC=0.727, P=0.001) and 18.55 mg/L (AUC=0.708, P=0.003), respectively. The best predictive value of DLA for diarrhea was 17.63 mg/L (AUC=0.920, P<0.001). The best predictive value of DLA for nutritional deterioration was 12.77 mg/L (AUC=0.684, P=0.006). Conclusion Intestinal barrier function indicators (DAO, DLA, and ET) have predictive value for vomiting, diarrhea, elevated transaminase and nutritional deterioration after chemotherapy.
Key words:  gastrointestinal neoplasms  intestinal barrier  chemotherapy  drug-related side effects and adverse reactions  nutritional status