【作者】 李杰；

【导师】 牛俊奇；

【作者基本信息】 吉林大学 ， 临床医学硕士（内科学）（专业学位）， 2021， 硕士

【摘要】 目的:(1)研究超声引导下微波消融术治疗肝肿瘤后肾脏等器官并发症发生情况及相关影响因素(2)通过对危险因素的分析,优化肝肿瘤微波消融治疗的相关措施,减少微波消融术后对肾脏等脏器的损害。方法:搜集2014年8月至2020年10月在吉林大学第一医院肝胆胰内科住院符合纳入和排除标准,行微波消融治疗肝脏肿瘤的病例,我们首先对2014年-2019年收录的病例进行了探索性研究,在此基础上,我们对2019年10以后收录的病历进行了验证性的研究,病例收录截止2020年10月。通过查阅患者病案信息系统,采集了患者基本临床资料及术前实验室化验指标,整理了相关数据资料,通过统计软件进行一般临床资料的基本分析,然后分析了各种严重并发症的基本特征及其出现的危险因素,重点关注病人的肾脏功能情况,探索临床资料和实验室化验结果有无差异。然后采用单因素Logistic回归分析和多因素Logistic回归分析方法探究引起严重并发症及急性肾损伤发生的危险因素;对术后急性肾损伤的不同指标进行诊断价值分析。最后对危险因素的诊断价值进行验证。结果:1.微波消融术后严重并发症的探索性研究(1)在本次研究中,共1142例病人于我科行微波消融治疗,我们对2019年10月之前的患者术后严重并发症发生情况进行了探索性研究;根据纳入及排除标准,847例患者纳入研究,其中男性病人624例,占74.0%,女性223例占26.0%;年龄>65岁180例,占21.0%,年龄≤65岁667例,占79.0%,最小患者年龄23岁,最大患者年龄83岁;原发性肝癌819例,占96.7%,转移性肝癌26例,占3.1%,良性肿瘤2例,占0.2%;微波消融患者逐年大体呈增加趋势:2014年治疗患者19例,2015年56例,2016年120例,2017年150例,2018年282例,2019年220例。(2)超声引导下微波消融术后出现严重并发症57例,发生率为6.73%(57/847),主要为急性肾损伤的有30例(3.5%),出血15例(1.8%),感染7例(0.8%),邻近脏器的损伤1例(0.1%),其他并发症4例(0.5%),分别为肝性脑病1例,心律失常-房室传导阻滞1例,不完全性小肠梗阻2例。(3)微波消融治疗的患者术后出现严重并发症有57例,其中男性多于女性,其中男性45例,女性12例;年龄多在65岁以下,其中年龄≤65岁有41例,年龄>65岁有16例;肿瘤多为单发病灶,其中单发肿瘤病灶36例,多发肿瘤病灶21例;在肝癌的类型方面,原发性肝癌最多,其中原发性肝癌54例,转移性肝癌2例,良性肝肿瘤1例;肿瘤最大直径多在30mm以下,其中34例肿瘤最大直径≤30mm,20例介于30与50mm之间,3例>50mm;Child-Pugh分级多为A级,A级35例,B级22例。(4)根据纳入标准,即微波消融术后有无严重并发症分为并发症组和无并发症组,对纳入患者的一般临床资料和实验室化验指标进行统计学分析,包括年龄、性别、肿瘤最大直径、肿瘤个数、消融能量、消融时间、Child-pugh分级、术前实验室指标(AFP、AST、ALT、ALB、TBil、K~+、Na~+、WBC、RBC、Hb、PLT、PT、INR、PTA、FBG);一般临床资料分析结果提示两组之间肿瘤性质方面存在差异,具有统计学意义(P<0.05);并发症组肿瘤最大直径、消融能量、消融时间明显高于非并发症组(P<0.05);术前实验室指标分析结果提示并发症组Na~+水平显著低于无并发症组(P<0.05)。(5)进一步探究微波消融术后并发症发生的危险因素,上述统计分析结果显示肿瘤性质、肿瘤最大直径、消融时间、消融能量、血清钠对术后严重并发症的发生有统计学意义。进行多因素Logistic回归分析,并通过使用向后法估计优势比(OR)和95%置信区间(CI),结果表明消融时间、血清钠水平是微波消融术后严重并发症发生的危险因素,即消融时间长,血清钠水平低微波消融术后严重并发症发生的危险高。(6)本研究中有2例患者微波消融术后死亡,死亡率为0.24%(2/847)。2.微波消融术后急性肾损伤的探索性研究(1)在微波消融术后严重并发症的841例病人中,对有完整肾脏功能检测的病人进行了急性肾损伤分析。根据纳入及排除标准,486例纳入本研究。其中包括男性354例(72.8%),女性132例(27.2%);年龄≤65岁376例(77.4%),年龄>65岁110例(22.6%),年龄最小23岁,最大87岁;肿瘤个数单发330例(67.9%),多发157例(32.1%);原发性肝癌463例(95.3%),转移性肝癌21例(4.3%),良性肿瘤2例(0.4%);肿瘤最大直径≤30mm 36例(74.7%),介于30mm与50mm之间110例(22.6%),>50mm 13例(2.7%);Child-up A级309例(63.6%),B级177例(36.4%)。(2)微波消融术后出现急性肾损伤的有30人,急性肾损伤的发生率为6.17%(30/486)。(3)对纳入患者消融治疗前的一般临床资料及实验室指标进行分组比较。一般临床资料分析结果表明急性肾损伤组与非急性肾损伤组在肿瘤性质、肿瘤最大直径方面存在差异,有统计学意义(P<0.05);急性肾损伤组比非急性肾损伤组消融能量更高、消融时间更长。在术前实验室检查结果分析中,急性肾损伤组RBC、Hb、PTA水平高于非急性肾损伤组。(4)进一步探究微波消融术后急性肾损伤的危险因素,先进行以Logistic单因素分析,结果提示肿瘤最大直径、消融时间(lg)、消融能量(lg)、术前红细胞、血红蛋白对术后急性肾损伤发生存在差异,具有统计学意义;接着采用向后法,纳入Logistic多因素回归分析,结果表明消融能量高、术前血红蛋白水平高是急性肾损伤发生的独立危险因素。(5)应用受试者工作特征曲线(ROC曲线)对消融能量与术前血红蛋白的诊断价值进行对比,消融能量(lg)的曲线下面积分别为0.731和0.661,消融能量具有更好的预测价值。3.微波消融术后急性肾损伤验证性研究(1)上述研究结果提示消融能量(lg)的截断值为4.927,本研究中选取整数5作为分组依据,将纳入患者分为消融能量(lg)≤5组与消融能量(lg)>5组两组;观察在2019.10-2020.10期间行超声引导下微波消融的肝肿瘤的两组患者,术后是否出现急性肾损伤;本研究共纳入294例病人,男性219例,女性75例,年龄≤65岁227例,>65岁76例,单发肿瘤病灶211例,多发肿瘤病灶83例;Child-Pugh分级A级189例,B级105例;原发性肝癌272例,转移性肝癌18例,良性结节3例;肿瘤最大直径≤30mm 222例,介于30与50mm之间69例,>50mm3例。(2)对纳入的294例患者的一般临床资料及术前实验室指标进行统计分析,结果提示两组之间肿瘤个数、糖尿病史、肿瘤最大直径、肿瘤类型、消融时间存在差异,消融能量(lg)>5组中单发的肿瘤个数明显低于消融能量(lg)≤5组;消融能量(lg)>5组与消融能量(lg)≤5组相比糖尿病史少,肿瘤最大直径偏大、消融时间长(P<0.05)。(3)消融能量(lg)>5组术后发生急性肾损伤的比例(10.0%)明显高于消融能量(lg)≤5组(1.5%);进行统计分析,P=0.025,说明消融能量(lg)可以用来预测术后急性肾损伤发生的风险。(4)消融能量(lg)作为诊断标准的灵敏度为0.429,特异度为0.906。结论:研究发现肝肿瘤超声引导下微波消融相对安全,但仍有一定的并发症发生,个别严重者会危及生命;消融时间长、低Na水平是微波消融术后主要并发症发生的危险因素。消融术后急性肾损伤发生率较高,消融能量增加、术前血红蛋白升高是急性肾衰竭发生的独立危险因素;消融能量(lg)对微波消融术后急性肾损伤的预测价值优于术前血红蛋白。更多还原

【Abstract】 Object:(1)To study the occurrence of kidney and other organ complications and the related influencing factors after ultrasound-guided microwave ablation for liver tumors.(2)To optimize the measures related to microwave ablation treatment of liver tumors through the analysis of risk factors and reduce the damage to kidneys and other organs after microwave ablation.Method:To collect cases that met the inclusion and exclusion criteria for hospitalization in the Department of Hepatology of the First Hospital of Jilin University from August 2014 to October 2020 for microwave ablation of liver tumors,we first conducted an exploratory study of cases included from 2014-2019,based on which we conducted a validation study of medical records included after October 2019,with cases included until October 2020.By reviewing the patient case information system,basic clinical information and preoperative laboratory laboratory test indexes were collected,relevant data and information were compiled,and the basic analysis of general clinical information was performed by statistical software,and then the basic characteristics of various serious complications and their risk factors for emergence were analyzed,focusing on the renal function of the patients to explore whether there were differences between clinical information and laboratory test results.Then single-factor logistic regression analysis and multi-factor logistic regression analysis were used to explore the risk factors for the occurrence of serious complications and acute kidney injury;the diagnostic value of different indicators of postoperative acute kidney injury was analyzed.Finally,the diagnostic value of the risk factors was verified.Results:Exploratory study of serious complications after microwave ablation(1)In this study,a total of 1142 patients underwent microwave ablation in our department,and we conducted an exploratory study on the occurrence of serious postoperative complications in patients before October 2019;according to the inclusion and exclusion criteria,847 patients were included in the study,including 624 male patients,accounting for74.0%,223 female patients,accounting for 26.0%;180 patients aged>65 years,accounting for 21.0%,age≤65 years old 667 cases,accounting for 79.0%,the youngest patient age 23years old,the oldest patient age 83 years old;primary liver cancer 819 cases,accounting for96.7%,metastatic liver cancer 26 cases,accounting for 3.1%,benign tumor 2 cases,accounting for 0.2%;microwave ablation patients year by year largely increased trend:19patients treated in 2014,56 cases in 2015,120 cases in 2016,120 cases in 2017.In 2016,120cases,150 cases in 2017,282 cases in 2018 and 220 cases in 2019.(2)There were 57 cases of serious complications after ultrasound-guided microwave ablation,with an incidence of 6.73%(57/847),mainly acute kidney injury in 30 cases(3.5%),bleeding in 15 cases(1.8%),infection in 7 cases(0.8%),injury to adjacent organs in 1 case(0.1%),and other complications in 4 cases(0.5%),namely hepatic encephalopathy in 1 case,cardiac arrhythmia-Atrioventricular block 1 case,incomplete small bowel obstruction 2 cases.(3)There were 57 cases of serious postoperative complications in patients treated with microwave ablation,among which there were more men than women,including 45 cases of men and 12 cases of women;most of them were under 65 years of age,including 41 cases of age≤65 years of age and 16 cases of age>65 years of age;most of the tumors were single lesions,including 36 cases of single tumor lesions and 21 cases of multiple tumor lesions;in terms of the type of liver cancer,primary liver cancer was the most frequent Among them,54cases were primary liver cancer,2 cases were metastatic liver cancer,and 1 case was benign liver tumor;the maximum diameter of tumor was mostly below 30 mm,among which 34 cases were≤30 mm,20 cases were between 30 and 50 mm,and 3 cases were>50 mm;Child-Pugh classification was mostly A grade,35 cases were A grade and 22 cases were B grade.(4)According to the inclusion criteria,i.e.whether there were serious complications after microwave ablation,the patients were divided into complication group and no complication group,and the general clinical data and laboratory laboratory indexes of the included patients were statistically analyzed,including age,gender,maximum tumor diameter,number of tumors,ablation energy,ablation time,Child-Pugh grade,preoperative laboratory indexes(AFP,AST,ALT,ALB,TBil,K+,Na+,WBC,RBC,Hb,PLT,PT,INR,PTA,FBG);the results of the analysis of general clinical data suggested that there were differences in the nature of tumors between the two groups,which were statistically significant(P<0.05);the maximum tumor diameter,ablation energy and ablation time were significantly higher in the group with complications than in the group without complications(P<0.05).The results of preoperative laboratory index analysis suggested that the Na+level in the group with complications was significantly lower than that in the group without complications(P<0.05).(5)To further investigate the risk factors for the occurrence of complications after microwave ablation,the results of the above statistical analysis showed that tumor nature,maximum tumor diameter,ablation time,ablation energy,and serum sodium were statistically significant for the occurrence of serious postoperative complications.Multi-factor logistic regression analysis was performed,and the dominance ratio(OR)and 95%confidence interval(CI)were estimated by using the backward method,and the results showed that ablation time and serum sodium level were the risk factors for the occurrence of serious complications after microwave ablation,i.e.,long ablation time and low serum sodium level had a high risk of serious complications after microwave ablation.(6)In this study,there were 2 patients who died after microwave ablation,with a mortality rate of 0.24%(2/847).2.An exploratory study of acute renal injury after microwave ablation(1)Among the 841 patients with severe complications after microwave ablation,those with intact renal function tests were analyzed for acute kidney injury.According to the inclusion and exclusion criteria,486 cases were included in this study.These included 354cases(72.8%)in men and 132 cases(27.2%)in women;376 cases(77.4%)aged≤65 years,110 cases(22.6%)aged>65 years,with a minimum age of 23 years and a maximum age of 87years;330 cases(67.9%)with single tumor and 157 cases(32.1%)with multiple tumors;463cases(95.3%)with primary hepatocellular carcinoma The maximum tumor diameter was≤30mm in 36 cases(74.7%),between 30 mm and 50 mm in 110 cases(22.6%),>50 mm in 13cases(2.7%);Child-up grade A in 309 cases(63.6%),grade B in 177 cases(36.4%).(2)Post-microwave ablation(2)There were 30 patients who developed acute kidney injury after microwave ablation,and the incidence of acute kidney injury was 6.17%(30/486).(3)The general clinical data and laboratory indices of the included patients before ablation treatment were compared in groups.The results of the analysis of general clinical data showed that there were statistically significant differences between the acute kidney injury group and the non-acute kidney injury group in terms of tumor nature and maximum tumor diameter(P<0.05);the acute kidney injury group had higher ablation energy and longer ablation time than the non-acute kidney injury group.In the analysis of preoperative laboratory test results,the levels of RBC,Hb and PTA in the acute kidney injury group were higher than those in the non-acute kidney injury group.(4)To further investigate the risk factors of acute kidney injury after microwave ablation,a logistic one-way analysis was first performed,and the results suggested that there were differences in the maximum tumor diameter,ablation time(lg),ablation energy(lg),preoperative red blood cells,and hemoglobin on the occurrence of postoperative acute kidney injury,which were statistically significant;then a backward method was used to incorporate logistic multi-factor regression analysis,the results indicated that high ablation energy and high preoperative hemoglobin level were independent risk factors for the occurrence of acute kidney injury.(5)The diagnostic value of ablation energy and preoperative hemoglobin was compared by applying the subject operating characteristic curve(ROC curve),and the area under the curve of ablation energy(lg)was 0.731 and 0.661,respectively,and the ablation energy had better predictive value.3.Validation study of acute kidney injury after microwave ablation(1)The results of the above study suggest that the cut-off value of ablation energy(lg)is4.927.In this study,the integer 5 was selected as the basis for grouping,and the included patients were divided into two groups:ablation energy(lg)≤5 and ablation energy(lg)>5;to observe whether acute kidney injury occurred after surgery in the two groups of patients who underwent ultrasound-guided microwave ablation of liver tumors during 2019.10-2020.10 The study included 294 patients,219 males and 75 females,227 aged≤65 years,76aged>65 years,211 with single tumor lesions and 83 with multiple tumor lesions;189 with Child-Pugh grade A and 105 with grade B;272 with primary liver cancer,18 with metastatic liver cancer,and 3 with benign nodules;the maximum tumor diameter was≤30 mm 222 cases,between 30 and 50 mm 69 cases,>50 mm 3 cases.(2)Statistical analysis of the general clinical data and preoperative laboratory indexes of the included 294 patients indicated that there were differences in the number of tumors,history of diabetes,maximum tumor diameter,tumor type,and ablation time between the two groups,and the number of single tumors in the ablation energy(lg)>5 group was significantly lower than that in the ablation energy(lg)≤5 group;the number of tumors in the ablation energy(lg)>5 group was lower than that in the ablation energy(lg)≤5 group,and the number of tumors in the ablation energy(lg)>5 group was lower than that in the ablation energy(lg)≤5 group.The ablation energy(lg)>5 group had less history of diabetes,larger maximum tumor diameter and longer ablation time compared with the ablation energy(lg)≤5 group(P<0.05).(3)The proportion of postoperative acute kidney injury occurred in the ablation energy(lg)>5 group(10.0%)was significantly higher than that in the ablation energy(lg)≤5 group(1.5%);for statistical analysis,P=0.025,indicating that ablation energy(lg)can be used to predict the risk of postoperative acute kidney injury.(4)The sensitivity of ablation energy(lg)as a diagnostic criterion was 0.429,and the specificity was 0.906.Conclusion:Ultrasound-guided microwave ablation of liver tumors was found to be relatively safe,but there were still some complications,some of which were life-threatening in severe cases.Long ablation time and low Na~+level are the main risk factors for complications after microwave ablation.The incidence of acute renal injury after ablation was higher,and the increased ablation energy and preoperative hemoglobin were independent risk factors for the occurrence of acute renal failure.Ablation energy(lg)is better than preoperative hemoglobin in predicting acute kidney injury after microwave ablation.更多还原