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肝细胞癌精准肝切除术后早期肠内营养与联合营养支持治疗的前瞻性研究

A prospective study of early enteral nutrition and combined enteral nutrition and parenteral nutrition in patients with hepatocellular carcinoma after precise hepatectomy

摘要:

目的 比较肝细胞癌精准肝切除术后早期单纯肠内营养与联合营养支持治疗的临床价值.方法 采用前瞻性研究方法.选取2013年1月至2014年12月南京大学医学院附属鼓楼医院收治的60例行精准肝切除术肝细胞癌患者的临床资料.采用随机数字表法将患者分为肠内组和联合组,肠内组患者术后早期采用肠内营养支持治疗,联合组患者术后早期采用肠内肠外联合营养支持治疗.两组均于术后24 h开始给予营养支持治疗,营养摄入总量保持一致,日均补氮量为0.2 g/(kg·d),日均非蛋白质热量为25 kcal/(kg·d),共7d.观察指标:(1)两组患者营养指标比较.(2)两组患者肝功能比较.(3)两组患者术后情况比较.正态分布的计量资料以-x±s表示,组间同一时间比较采用两组间成组设计t检验.计数资料比较采用x2检验.等级资料比较采用非参数检验.重复测量数据采用重复测量方差分析.结果 筛选出符合研究条件的患者60例,肠内组和联合组各30例.(1)两组患者营养指标比较:肠内组患者Alb术前、术后第1天和术后第8天分别为(41±4)g/L、(32±4)g/L、(34±5)g/L,球蛋白分别为(28±4)g/L、(23±5) g/L、(26±4)g/L,前白蛋白分别为(188±37) mg/L、(114±41) mg/L、(169±41) mg/L,Hb分别为(139±17) g/L、(121±19)g/L、(113±16)g/L,淋巴细胞计数分别为(1.6±0.6)×109/L、(1.1±0.7)×109/L、(1.9±1.1)×109/L.上述指标术前、术后第1天、术后第8天比较,差异均有统计学意义(F=2.23,4.45,8.96,5.21,2.18,P<0.05).上述指标术前与术后第1天分别比较,差异均有统计学意义(t=9.79,8.53,9.81,4.56,5.77,P<0.05).Alb、球蛋白、前白蛋白、Hb术前与术后第8天分别比较,差异均有统计学意义(t=3.48,5.12,6.37,8.20,P<0.05),淋巴细胞计数比较,差异无统计学意义(t=2.48,P>0.05).上述指标术后第1天与术后第8天分别比较,差异均有统计学意义(t=5.55,6.31,4.69,3.99,8.26,P<0.05).联合组患者Alb术前、术后第1天和术后第8天分别为(42±4)g/L、(31±5)g/L、(34±4)g/L,球蛋白分别为(28±6) g/L、(20±5)g/L、(24±4) g/L,前白蛋白分别为(188±29) g/L、(96±31)g/L、(143±18) g/L,Hb分别为(142±16) g/L、(124±16) g/L、(115±18)g/L,淋巴细胞计数分别为(1.6±0.6)×109/L、(0.9±0.4)×109/L、(1.4±0.7)×109/L.上述指标术前、术后第1天、术后第8天比较,差异均有统计学意义(F=3.21,7.35,4.36,7.78,3.19,P<0.05).上述指标术前与术后第1天分别比较,差异均有统计学意义(t=11.95,5.38,9.91,4.84,6.22,P<0.05).Alb、球蛋白、前白蛋白、Hb术前与术后第8天比较,差异均有统计学意义(t=9.31,8.44,6.57,5.25,P<0.05),淋巴细胞计数比较,差异无统计学意义(t=3.11,P>0.05).上述指标术后第1天与术后第8天分别比较,差异均有统计学意义(t=9.45,7.66,4.98,3.15,4.79,P<0.05).两组患者Alb、球蛋白、前白蛋白、Hb、淋巴细胞计数变化趋势比较,差异均无统计学意义(F=8.54,3.83,7.21,6.33,3.91,P>0.05).术后第8天前白蛋白比较,差异有统计学意义(t=3.00,P<0.05).(2)两组患者肝功能比较:肠内组患者ALT术前、术后第1天、术后第8天分别为(44±37) U/L、(411±375)U/L、(107±58) U/L,AST为(44±30) U/L、(379±323) U/L、(43±21) U/L,ALP分别为(90±29) U/L、(68±26) U/L、(100±42)U/L,GGT分别为(85±49) U/L、(55±49) U/L、(111±71) U/L,TBil分别为(15.7±5.4)μmol/L、(20.3±10.7)μmol/L、(19.7±10.6)μmol/L,DBil分别为(4.6±2.3)μmol/L、(7.8±5.5) μmol/L、(8.8±5.9)μmol/L,C反应蛋白(CRP)分别为(4.5±3.2) mg/L、(47.9±30.6)mg/L、(28.3±23.0)mg/L.上述指标术前、术后第1天、术后第8天比较,差异均有统计学意义(F=5.48,9.44,1.73,5.03,8.42,6.09,6.69,P<0.05).术前与术后第1天分别比较,差异均有统计学意义(t=5.12,5.36,5.35,0.45,2.88,3.82,6.95,P<0.05).ALT、TBil、DBil、CRP术前与术后第8天比较,差异均有统计学意义(t=6.71,4.14,5.96,6.33,P<0.05),AST、ALP、GGT分别比较,差异均无统计学意义(t=0.13,0.98,1.11,P>0.05).ALT、AST、ALP、GGT、CRP术后第1天与术后第8天分别比较,差异均有统计学意义(t=6.23,5.55,3.14,3.56,4.99,P<0.05),TBil、DBil分别比较,差异均无统计学意义(t=0.08,0.23,P>0.05).联合组患者ALT术前、术后第1天、术后第8天分别为(41±38) U/L、(462±409) U/L、(90±47) U/L,AST为(43±25) U/L、(494±162) U/L、(42±16) U/L,ALP分别为(100±89) U/L、(73±53)U/L、(95±40)U/L,GGT分别为(106±46) U/L、(75±57) U/L、(110±66) U/L,TBil分别为(17.9±9.8)μmol/L、(28.1±18.8) μmol/L、(22.5±14.5)μmol/L,DBil分别为(6.2±3.6)μmol/L、(9.1±6.1)μmol/L、(8.2±8.1)μmol/L,CRP分别为(3.7±2.3)mg/L、(40.7±26.2)mg/L、(26.9±24.6)mg/L.上述指标术前、术后第1天、术后第8天比较,差异均有统计学意义(F=5.96,3.73,6.94,3.88,7.97,4.14,5.25,P<0.05).上述指标术前与术后第1天分别比较,差异均有统计学意义(t=5.72,4.96,3.95,0.88,2.83,4.13,6.11,P<0.05).ALT、CRP术前与术后第8天分别比较,差异均有统计学意义(t=4.22,6.77,P<0.05),AST、ALP、GGT、TBil、DBil分别比较,差异均无统计学意义(t=0.29,1.65,1.92,0.33,P>0.05).ALT、AST、ALP、GGT术后第1天与术后第8天分别比较,差异均有统计学意义(t=7.01,5.21,4.38,6.15,P<0.05),TBil、DBil、CRP分别比较,差异均无统计学意义(t=0.09,0.37,0.58,P>0.05).两组患者ALT、AST、ALP、GGT、TBil、DBil、CRP变化趋势比较,差异均无统计学意义(F=7.18,2.23,3.94,5.88,4.72,2.17,6.53,P>0.05).上述指标术前、术后第1天、术后第8天分别比较,差异均无统计学意义(t=0.27,0.42,0.91,0.12,0.96,0.24,0.59,0.32,0.49,1.27,0.88,0.07,1.07,1.45,0.23,1.11,0.88,0.32,0.35,0.93,0.21,P>0.05).(3)两组患者术后情况比较:肠内组和联合组患者术后首次排便时间分别为(3.2±1.0)d和(4.2±1.2)d,两组比较,差异有统计学意义(t=3.21,P<0.05).结论 肝细胞癌精准肝切除术后早期单纯肠内营养与联合营养支持治疗均安全可行,两者促进肝功能恢复相似,但肠内营养支持治疗具有促进肝脏蛋白质合成和胃肠功能恢复的优势.

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abstracts:

Objeetive To compare the clinical value of early enteral nutrition (EEN) and combined enteral nutrition (EN) and parenteral nutrition (PN) in patients with hepatocellular carcinoma (HCC) after precise hepatectomy.Methods The prospective study was conducted.The clinical data of 60 HCC patients who underwent precise hepatectomy in the Affiliated Drum Tower Hospital of Nanjing University Medical School between January 2013 and December 2014 were collected.All patients were allocated into the EN group and combined EN+PN group by random number table method.Patients in the EN group and combined EN+PN group respectively received EEN and early combined EN+PN at 24 hours postoperatively for 7 days,total nutrient intakes between groups were consistent,with an average daily intake of nitrogen-feeding of 0.2 g/(kg · d) and an average daily intake of nonprotein calories of 25 kcal/(kg · d).Observation indicators:(1) comparison of nutritional indexes between groups;(2) comparison of liver function between groups;(3) comparison of postoperative conditions between groups.Measurement data with normal distribution were represented as-x±s.Comparisons at the same time between groups were respectively analyzed using the group-design t test.Comparisons of count data were analyzed using the chi-square test.Ordinal data were analyzed by the nonparametric test.Comparison of repeated measurement data were done using the repeated measures ANOVA.Results Sixty patients were screened for eligibility,and 30 in each group.(1) Comparison of nutritional indexes between groups:levels of albumin (Alb),globulin,prealbumin and hemoglobin (Hb) and lymph nodes count in the EN group were respectively (41±4)g/L,(28±4) g/L,(188±37) mg/L,(139± 17) g/L,(1.6±0.6) × 109/L before operation and (32±4) g/L,(23±5)g/L,(114±41)mg/L,(121±19)g/L,(1.1±0.7) ×109/L at 1 day postoperative1y and (34±5)g/L,(26±4) g/L,(169± 41) mg/L,(113 ± 16) g/L,(1.9 ± 1.1) × 109/L at 8 days postoperatively,with statistically significant differences in above indexes (F=2.23,4.45,8.96,5.21,2.18,P<0.05).There were statistically significant differences in above indexes between pre-operation and 1 day postoperatively (t =9.79,8.53,9.81,4.56,5.77,P<0.05) and between 1 and 8 days postoperatively (t =5.55,6.31,4.69,3.99,8.26,P<0.05).There were statistically significant differences in levels of Alb,globulin,prealbumin and Hb between pre-operation and 8 days postoperatively (t=3.48,5.12,6.37,8.20,P<0.05) and no statistically significant difference in lymph nodes count (t =2.48,P>0.05).Levels of Alb,globulin,prealbumin and Hb and lymph nodes count in the combined EN+PN group were respectively (42±4)g/L,(28±6)g/L,(188±29)g/L,(142±16)g/L,(1.6±0.6)×109/L before operation and (31±5)g/L,(20±5) g/L,(96±31) g/L,(124± 16) g/L,(0.9±0.4) × 109/L at 1 day postoperatively and (34±4)g/L,(24±4)g/L,(143±18)g/L,(115±18)g/L,(1.4±0.7)×109/L at 8 days postoperatively,with statistically significant differences in above indexes (F=3.21,7.35,4.36,7.78,3.19,P<0.05).There were statistically significant differences in above indexes between pre-operation and 1 day postoperatively (t =11.95,5.38,9.91,4.84,6.22,P<0.05) and between 1 and 8 days postoperatively (t =9.45,7.66,4.98,3.15,4.79,P< 0.05).There were statistically significant differences in levels of Alb,globulin,prealbumin and Hb between pre-operation and 8 days postoperatively (t=9.31,8.44,6.57,5.25,P<0.05).There were no statistically significant difference in lymph nodes count (t =3.11,P> 0.05) and in changing trends of Alb,globulin,prealbumin,Hb and lymph nodes count (F=8.54,3.83,7.21,6.33,3.91,P>0.05).Levels of prealbumin at 8 days postoperatively were statistically different between groups (t =3.00,P<0.05).(2) Comparison of liver function between groups:levels of alanine transaminase (ALT),aspartate transaminase (AST),alkaline phosphatase (ALP),glutamyl-transpeptidase (GGT),total bilirubin (TBil),direct bilirubin (DBil) and C-reactive protein (CRP) in the EN group were respectively (44±37)U/L,(44±30) U/L,(90± 29) U/L,(85 ± 49) U/L,(15.7± 5.4) μmol/L,(4.6± 2.3) μmol/L,(4.5 ± 3.2) mg/L before operation and (411±375)U/L,(379±323)U/L,(68±26)U/L,(55±49)U/L,(20.3±10.7)μmol/L,(7.8±5.5) μmol/L,(47.9± 30.6) mg/L at 1 day postoperatively and (107± 58) U/L,(43± 21) U/L,(100± 42) U/L,(111±71)U/L,(19.7±10.6) μmol/L,(8.8±5.9) μmol/L,(28.3±23.0) mg/L at 8 days postoperatively,with statistically significant differences in above indexes among pre-operation,1 and 8 days postoperatively (F=5.48,9.44,1.73,5.03,8.42,6.09,6.69,P<0.05) and between pre-operation and 1 day postoperatively (t=5.12,5.36,5.35,0.45,2.88,3.82,6.95,P< 0.05).There were statistically significant differences in levels of ALT,TBil,DBil and CRP between pre-operation and 8 days postoperatively (t =6.71,4.14,5.96,6.33,P<0.05) and in levels of ALT,AST,ALP,GGT and CRP between 1 and 8 days postoperatively (t =6.23,5.55,3.14,3.56,4.99,P<0.05).There were no statistically significant difference in levels of AST,ALP and GGT (t =0.13,0.98,1.11,P>0.05) and in levels of TBil and DBil (t =0.08,0.23,P>0.05).Levels of ALT,AST,ALP,GGT,TBil,DBil and CRP in the combined EN+PN group were respectively (41±38) U/L,(43±25) U/L,(100±89) U/L,(106±46) U/L,(17.9±9.8) μmol/L,(6.2±3.6) μmol/L,(3.7±2.3)mg/L before operation and (462±409)U/L,(494±162)U/L,(73±53)U/L,(75±57)U/L,(28.1±18.8)μmol/L,(9.1±6.1) μmol/L,(40.7±26.2) mg/L at 1 day postoperatively and (90±47) U/L,(42± 16) U/L,(95±40) U/L,(110±66) U/L,(22.5± 14.5) μmol/L,(8.2±8.1) μmol/L,(26.9±24.6) mg/L at 8 days postoperatively,with statistically significant differences in above indexes among pre-operation,1 and 8 days postoperatively (F=5.96,3.73,6.94,3.88,7.97,4.14,5.25,P<0.05) and between before operation and 1 day postoperatively (t=5.72,4.96,3.95,0.88,2.83,4.13,6.11,P<0.05).There were statistically significant differences in levels of ALT and CRP between pre-operation and 8 days postoperatively (t =4.22,6.77,P<0.05) and in levels of ALT,AST,ALP and GGT between 1 and 8 days postoperatively (t=7.01,5.21,4.38,6.15,P<0.05).There were no statistically significant difference in levels of AST,ALP,GGT,TBil and DBil (t =0.29,1.65,1.92,0.33,P>0.05) and in levels of TBil,DBil and CRP (t =0.09,0.37,0.58,P>0.05).There was no statistically significant difference in changing trends of ALT,AST,ALP,GGT,TBil,DBil and CRP of 2 groups (F=7.18,2.23,3.94,5.88,4.72,2.17,6.53,P>0.05) and in above indexes among pre-operation,1 and at 8 days postoperatively (t=0.27,0.42,0.91,0.12,0.96,0.24,0.59,0.32,0.49,1.27,0.88,0.07,1.07,1.45,0.23,1.11,0.88,0.32,0.35,0.93,0.21,P>0.05).(3) Comparison of postoperative conditions between groups:times of initial defecation were respectively (3.2± 1.0) days and (4.2± 1.2) days in the EN group and combined EN +PN group,showing a statistically significant difference (t =3.21,P< 0.05).Conclusion EEN and combined EN+PN are safe and feasible in HCC patients after precise hepatectomy,and also can improve liver function recovery,but EEN has advantages of promoting protein synthesis and gastrointestinal function recovery.

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