年龄调整的Charlson合并症指数影响腹腔镜胃癌根治术患者预后的多中心回顾性研究

Influences of age-adjusted Charlson comorbidity index on prognosis of patients undergoing laparoscopic radical gastrectomy:a multicenter retrospective study

目的探讨年龄调整的Charlson合并症指数(ACCI)对腹腔镜胃癌根治术患者预后的影响。方法采用回顾性队列研究方法。收集2016年9月至2017年10月中国腹腔镜胃肠外科研究组-04研究中19家医院收治的242例(福建医科大学附属协和医院54例、莆田市第一医院32例、上海交通大学医学院附属仁济医院32例、福建医科大学附属漳州市医院31例、南方医科大学南方医院17例、南京医科大学第一附属医院11例、青海大学附属医院8例、梅州市人民医院8例、福建省立医院7例、复旦大学附属中山医院6例、龙岩市第一医院6例、新疆医科大学附属第一医院5例、陆军军医大学第一附属医院5例、广州中医药大学第二附属医院4例、四川大学华西医院4例、北京大学肿瘤医院4例、厦门大学附属第一医院3例、广东省人民医院3例、西安交通大学第一附属医院2例)行腹腔镜胃癌根治术患者的临床病理资料;男193例,女49例;年龄为62(23~74)岁。观察指标:(1)患者年龄分布与合并症及ACCI情况。(2)ACCI分组及临床病理特征比较。(3)术后早期并发症发生情况及术后早期并发症影响因素分析。(4)随访情况。(5)影响患者3年无复发生存率的因素分析。采用门诊或电话方式进行随访,了解患者术后生存情况。随访时间截至2020年12月。正态分布的计量资料以x±s表示,组间比较采用t检验;偏态分布的计量资料以M(Q_(1),Q_(3))或M(范围)表示,组间比较采用Mann-Whitney U检验。计数资料以绝对数或百分比表示,组间比较采用χ^(2)检验或Fisher确切概率法。等级资料比较采用非参数秩和检验。采用X-Tile软件(3.6.1)分析ACCI分组临界值。采用Kaplan-Meier法计算生存率和绘制生存曲线,采用Log-Rank检验进行生存分析。采用Logistic回归模型分析术后早期并发症影响因素。采用COX比例风险模型进行3年无复发生存率影响的单因素和多因素分析,多因素分析以逐步回归法纳入P<0.05的单因素指标和临床上与预后密切相关的变量。结果(1)患者年龄分布与合并症及ACCI情况。242例患者中,<50岁28例,50~59岁68例,60~69岁113例,70~79岁33例;合并轻度肝病、伴有终末器官损害的糖尿病、脑血管疾病、消化性溃疡、充血性心力衰竭、慢性肺疾病、不伴终末器官损害的糖尿病分别为1、1、2、2、6、8、9例。242例患者ACCI为2(0~4)。(2)ACCI分组及其临床病理特征比较。X-Tile软件分析结果显示:ACCI=3为最佳分组临界值。根据ACCI最佳分组临界值将242例患者分为低ACCI组(ACCI<3)194例和高ACCI组(ACCI≥3)48例。低ACCI组患者年龄,体质量指数,术前合并症,美国麻醉医师协会分级(Ⅰ级、Ⅱ级、Ⅲ级),肿瘤长径,组织学类型(印戒细胞癌或低分化腺癌、中分化或高分化腺癌),肿瘤病理学T分期(T1期、T2期、T3期、T4期),化疗周期分别为(58±9)岁,(22.6±2.9)kg/m2,31例,106、85、3例,(4.0±1.9)cm,104、90例,16、29、72、77例,6(4,6)个;高ACCI组患者上述指标分别为(70±4)岁,(21.7±2.7)kg/m2,23例,14、33、1例,(5.4±3.1)cm,36、12例,3、4、13、28例,4(2,5)个;两组患者上述指标比较,差异均有统计学意义(t=-14.37、1.98,χ^(2)=22.64,Z=-3.11,t=-2.91,χ^(2)=7.22,Z=-2.21、-3.16,P<0.05)。(3)术后早期并发症发生情况及术后早期并发症影响因素分析。242例患者中,33例发生术后早期并发症,包括局部并发症20例,系统性并发症16例,部分患者同时合并多种并发症。20例局部并发症包括腹腔感染12例,吻合口漏7例,切口感染、腹腔出血、吻合口出血各2例,淋巴液漏1例。16例系统性并发症包括肺部感染11例,心律失常、脓毒血症各2例,肝衰竭、肾衰竭、肺动脉栓塞、深静脉血栓、尿路感染、尿潴留各1例。33例发生术后早期并发症患者Clavien-Dindo并发症分级Ⅰ级、Ⅱ级、Ⅲa级、Ⅲb级、Ⅳ级分别为3、22、5、2、1例。低ACCI组患者术后早期并发症、局部并发症、系统性并发症分别为22、13、9例;高ACCI组患者上述指标分别为11、7、7例;两组患者早期并发症、系统性并发症比较,差异均有统计学意义(χ^(2)=4.38,4.66,P<0.05);局部并发症比较,差异无统计学意义(χ^(2)=2.20,P>0.05)。Logistic回归分析结果显示:ACCI是影响腹腔镜胃癌根治术后发生早期并发症的相关因素(比值比=2.32,95%可信区间为1.04~5.21,P<0.05)。(4)随访情况。242例患者均获得随访,随访时间为36(1~46)个月。随访期间,53例患者死亡,13例带瘤生存。242例患者3年无复发生存率为73.5%。低ACCI组患者随访时间为36(2~46)个月,随访期间,29例患者死亡,10例带瘤生存,患者3年无复发生存率为80.0%;高ACCI组患者上述指标分别为35(1~42)个月,24、3例,47.4%;两组患者3年无复发生存率比较,差异有统计学意义(χ^(2)=30.49,P<0.05)。(5)影响患者3年无复发生存率的因素分析。单因素分析结果显示:术前合并症、ACCI、肿瘤长径、组织学类型、血管侵犯、淋巴管侵犯、神经侵犯、肿瘤病理学TNM分期、术后早期并发症是影响腹腔镜胃癌根治术后3年无复发生存率的相关因素(风险比=2.52,3.64,2.62,0.47,2.87,1.90,1.86,21.77,1.97,95%可信区间为1.52~4.17,2.22~5.95,1.54~4.46,0.27~0.80,1.76~4.70,1.15~3.12,1.10~3.14,3.01~157.52,1.11~3.50,P<0.05)。多因素分析结果显示:ACCI、肿瘤病理学TNM分期、辅助化疗是腹腔镜胃癌根治术后3年无复发生存率的独立影响因素(风险比=3.65,11.00,40.66,0.39,95%可信区间为2.21~6.02,1.40~86.73,5.41~305.69,0.22~0.68,P<0.05)。结论ACCI是影响腹腔镜胃癌根治术后发生早期并发症的相关因素,ACCI、肿瘤病理学TNM分期、辅助化疗是腹腔镜胃癌根治术后3年无复发生存率的独立影响因素。

Objective To investigate the influences of age-adjusted Charlson comorbidity index(ACCI)on prognosis of patients undergoing laparoscopic radical gastrectomy.Methods The retrospective cohort study was conducted.The clinicopathological data of 242 gastric cancer patients who underwent laparoscopic radical gastrectomy in 19 hospitals of the Chinese Laparoscopic Gastrointestinal Surgery Study Group-04 study,including 54 patients in Fujian Medical University Union Hospital,32 patients in the First Hospital of Putian City,32 patients in Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine,31 patients in Zhangzhou Affiliated Hospital of Fujian Medical University,17 patients in Nanfang Hospital of Southern Medical University,11 patients in the First Affiliated Hospital with Nanjing Medical University,8 patients in Qinghai University Affiliated Hospital,8 patients in Meizhou People′s Hospital,7 patients in Fujian Provincial Hospital,6 patients in Zhongshan Hospital of Fudan University,6 patients in Longyan First Hospital,5 patients in the First Affiliated Hospital of Xinjiang Medical University,5 patients in the First Hospital Affiliated to Army Medical University,4 patients in the Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine,4 patients in West China Hospital of Sichuan University,4 patients in Beijing University Cancer Hospital,3 patients in the First Affiliated Hospital of Xiamen University,3 patients in Guangdong Provincial People′s Hospital,2 patients in the First Affiliated Hospital of Xi′an Jiaotong University,from September 2016 to October 2017 were collected.There were 193 males and 49 females,aged 62(range,23‒74)years.Observation indicators:(1)age distribution,comorbidities and ACCI status of patients;(2)the grouping of ACCI and comparison of clinicopathological characteristics of patients in each group;(3)incidence of postoperative early complications and analysis of factors affecting postoperative early complications;(4)follow-up;(5)analysis of factors affecting the 3-year recurrence-free survival rate of patients.Follow-up was conducted using outpatient examination or telephone interview to detect postoperative survival of patients up to December 2020.Measurement data with normal distribution were represented as Mean±SD,and comparison between groups was conducted using the t test.Measurement data with skewed distribution were represented as M(Q_(1),Q_(3))or M(range),and comparison between groups was conducted using the Mann-Whitney U test.Count data were described as absolute numbers or percentages,and comparison between groups was conducted using the chi-square test or Fisher exact probability.Comparison of ordinal data was conducted using the nonparametric rank sum test.The X-Tile software(version 3.6.1)was used to analyze the best ACCI grouping threshold.The Kaplan-Meier method was used to calculate survival rates and draw survival curves.The Log-Rank test was used for survival analysis.The Logistic regression model was used to analyze the factors affecting postoperative early complications.The COX proportional hazard model was used for univariate and multivariate analyses of factors affecting the 3-year recurrence-free survival rate of patients.Multivariate analysis used stepwise regression to include variables with P<0.05 in univariate analysis and variables clinically closely related to prognosis.Results(1)Age distribution,comor-bidities and ACCI status of patients.Of the 242 patients,there were 28 cases with age<50 years,68 cases with age of 50 to 59 years,113 cases with age of 60 to 69 years,33 cases with age of 70 to 79 years.There was 1 patient combined with mild liver disease,1 patient combined with diabetes of end-organ damage,2 patients combined with peripheral vascular diseases,2 patients combined with peptic ulcer,6 patients combined with congestive heart failure,8 patients combined with chronic pulmonary diseases,9 patients with diabetes without end-organ damage.The ACCI of 242 patients was 2(range,0-4).(2)The grouping of ACCI and comparison of clinicopathological characteristics of patients in each group.Results of X-Tile software analysis showed that ACCI=3 was the best grouping threshold.Of the 242 patients,194 cases with ACCI<3 were set as the low ACCI group and 48 cases with ACCI≥3 were set as the high ACCI group,respectively.Age,body mass index,cases with preoperative comorbidities,cases of American Society of Anesthesiologists classification as stageⅠ,stageⅡ,stageⅢ,tumor diameter,cases with tumor histological type as signet ring cell or poorly differentiated adenocarcinoma and cases with tumor type as moderately or well differentiated adenocarcinoma,cases with tumor pathological T staging as stage T1,stage T2,stage T3,stage T4,chemotherapy cycles were(58±9)years,(22.6±2.9)kg/m2,31,106,85,3,(4.0±1.9)cm,104,90,16,29,72,77,6(4,6)in the low ACCI group,versus(70±4)years,(21.7±2.7)kg/m2,23,14,33,1,(5.4±3.1)cm,36,12,3,4,13,28,4(2,5)in the high ACCI group,showing significant differences in the above indicators between the two groups(t=-14.37,1.98,χ^(2)=22.64,Z=-3.11,t=-2.91,χ^(2)=7.22,Z=-2.21,-3.61,P<0.05).(3)Incidence of postoperative early complications and analysis of factors affecting postoperative early complications.Of the 242 patients,33 cases had postoperative early complications,including 20 cases with local complications and 16 cases with systemic complica-tions.Some patients had multiple complications at the same time.Of the 20 patients with local complications,12 cases had abdominal infection,7 cases had anastomotic leakage,2 cases had incision infection,2 cases had abdominal hemorrhage,2 cases had anastomotic hemorrhage and 1 case had lymphatic leakage.Of the 16 patients with systemic complications,11 cases had pulmonary infection,2 cases had arrhythmias,2 cases had sepsis,1 case had liver failure,1 case had renal failure,1 case had pulmonary embolism,1 case had deep vein thrombosis,1 case had urinary infection and 1 case had urine retention.Of the 33 cases with postoperative early complications,there were 3 cases with gradeⅠcomplications,22 cases with gradeⅡcomplications,5 cases with gradeⅢa complications,2 cases with gradeⅢb complications and 1 case with gradeⅣcomplica-tions of Clavien-Dindo classification.Cases with postoperative early complications,cases with local complications,cases with systemic complications were 22,13,9 in the low ACCI group,versus 11,7,7 in the high ACCI group,respectively.There were significant differences in cases with postoperative early complications and cases with systemic complications between the two groups(χ^(2)=4.38,4.66,P<0.05),and there was no significant difference in cases with local complications between the two groups(χ^(2)=2.20,P>0.05).Results of Logistic regression analysis showed that ACCI was a related factor for postoperative early complications of gastric cancer patients undergoing laparoscopic radical gastrectomy[odds ratio=2.32,95%confidence interval(CI)as 1.04-5.21,P<0.05].(4)Follow-up.All the 242 patients were followed up for 36(range,1‒46)months.During the follow-up,53 patients died and 13 patients survived with tumor.The 3-year recurrence-free survival rate of the 242 patients was 73.5%.The follow-up time,cases died and cases survived with tumor during follow-up,the 3-year recurrence-free survival rate were 36(range,2-46)months,29,10,80.0%for the low ACCI group,versus 35(range,1-42)months,24,3,47.4%for the high ACCI group.There was a significant difference in the 3-year recurrence-free survival rate between the two groups(χ^(2)=30.49,P<0.05).(5)Analysis of factors affecting the 3-year recurrence-free survival rate of patients.Results of univariate analysis showed that preoperative comorbidities,ACCI,tumor diameter,histological type,vascular invasion,lymphatic invasion,neural invasion,tumor pathological TNM staging,postoperative early complications were related factors for postoperative 3-year recurrence-free survival rate of gastric cancer patients undergoing laparoscopic radical gastrectomy[hazard ratio(HR)=2.52,3.64,2.62,0.47,2.87,1.90,1.86,21.77,1.97,95%CI as 1.52-4.17,2.22-5.95,1.54-4.46,0.27-0.80,1.76-4.70,1.15-3.12,1.10-3.14,3.01-157.52,1.11-3.50,P<0.05].Results of multivariate analysis showed that ACCI,tumor pathological TNM staging,adjuvant chemotherapy were indepen-dent influencing factors for postoperative 3-year recurrence-free survival rate of gastric cancer patients undergoing laparoscopic radical gastrectomy(HR=3.65,11.00,40.66,0.39,95%CI as 2.21-6.02,1.40-86.73,5.41-305.69,0.22-0.68,P<0.05).Conclusions ACCI is a related factor for post-operative early complications of gastric cancer patients undergoing laparos-copic radical gastrectomy.ACCI,tumor pathological TNM staging,adjuvant chemotherapy are indepen-dent influencing factors for postoperative 3-year recurrence-free survival rate of gastric cancer patients undergoing laparoscopic radical gastrectomy.