胃癌根治术后胰瘘发生率及其影响因素分析的多中心前瞻性研究(附2089例报告)

A multicenter prospective study on incidence and risk factors of postoperative pancreatic fistula after radical gastrectomy:a report of 2089 cases

目的探讨胃癌根治术后胰瘘发生率及其影响因素。方法采用前瞻性研究方法。选取2017年12月至2018年11月22家医疗中心收治的2089例(复旦大学附属中山医院380例、上海交通大学医学院附属仁济医院351例、上海交通大学医学院附属瑞金医院130例、北京大学肿瘤医院139例、福建省肿瘤医院128例、陆军军医大学第一附属医院114例、南昌大学第一附属医院104例、青海大学附属医院104例、潍坊市人民医院103例、福建医科大学附属协和医院102例、空军军医大学第一附属医院99例、浙江大学医学院附属邵逸夫医院97例、浙江大学医学院附属杭州市第一人民医院60例、复旦大学附属肿瘤医院48例、西安交通大学第一附属医院29例、丽水市中心医院26例、广东省人民医院26例、江苏省人民医院23例、中山大学附属第一医院13例、吉林大学第二医院7例、新疆医科大学第一附属医院4例、首都医科大学附属北京朝阳医院2例)行胃癌根治术患者的临床病理资料。观察指标:(1)胃癌根治术后胰瘘发生率情况。(2)胃癌根治术后B级胰瘘治疗情况。(3)临床病理资料分析。(4)手术特征资料分析。(5)影响胃癌根治术后B级胰瘘发生相关因素分析。正态分布的计量资料以±s表示,多组间比较采用方差分析;计数资料以绝对数或百分比表示,多组间比较采用χ2检验;剔除临床病理资料和手术特征资料的缺失数据后行单因素分析,单因素分析采用t检验或χ2检验,将P<0.20因素纳入多因素分析;多因素分析采用Logistic回归模型。结果筛选出符合研究条件患者2089例,男1512例,女576例,性别数据缺失1例;年龄为(62±11)岁,体质量指数(BMI)为(23±3)kg/m2。(1)胃癌根治术后胰瘘发生率情况:2089例患者胃癌根治术后胰瘘总发生率为20.728%(433/2089),生化瘘发生率为19.627%(410/2089),B级胰瘘发生率为1.101%(23/2089),C级胰瘘发生率为0。(2)胃癌根治术后B级胰瘘治疗情况:23例胃癌根治术后发生B级胰瘘患者中,2例引流管放置时间>21 d,予以抗感染治疗;4例影像学检查发现腹腔积液,其中2例经B超引导下腹腔穿刺引流,1例尝试穿刺引流失败,1例未行穿刺引流,均予以抗感染治疗;11例影像学检查未发现腹腔积液,但临床表现发热或实验室检查示白细胞升高,均予以抗感染、抑制胰酶分泌治疗;6例无典型临床表现,给予生长抑素以抑制胰酶分泌且腹腔引流管放置时间延长(中位时间为7 d)。23例患者经治疗后均顺利康复,未行二次手术治疗。(3)临床病理资料分析:2089例患者中,无胰瘘患者BMI,新辅助治疗(无、有)分别为(23±3)kg/m2,1487例、160例,生化瘘和B级胰瘘患者上述指标分别为(23±3)kg/m2,386例、22例和(24±3)kg/m2,22例、1例,3类患者上述指标比较,差异均有统计学意义(F=5.787,χ2=8.269,P<0.05)。(4)手术特征资料分析:2089例患者中,无胰瘘患者手术方式(开腹、腹腔镜辅助、全腹腔镜),淋巴结清扫范围(D1、D2、其他),网膜囊切除范围(未切除、部分切除、全部切除),能量设备使用(无、超声刀、LigaSure、LigaSure+超声刀),生物胶使用(无、有),淋巴结清扫数目分别为737例、624例、292例,24例、1580例、51例,418例、834例、381例,63例、1530例、23例、16例,1431例、201例,(33±14)枚,生化瘘和B级胰瘘患者上述指标分别为146例、189例、74例,11例、389例、9例,110例、171例、128例,35例、359例、6例、9例,378例、31例,(31±14)枚和14例、5例、4例,0、20例、3例,6例、13例、4例,2例、18例、1例、2例,22例、1例,(37±16)枚,3类患者上述指标比较,差异均有统计学意义(χ2=15.578,9.397,15.023,28.245,8.359,F=4.945,P<0.05)。(5)影响胃癌根治术后B级胰瘘发生相关因素分析。单因素分析结果显示:能量设备使用是影响胃癌根治术后B级胰瘘发生的相关因素(χ2=9.914,P<0.05)。多因素分析结果显示:腹腔镜辅助手术、联合脏器切除、使用LigaSure+超声刀、淋巴结清扫数目是胃癌根治术后B级胰瘘发生的独立影响因素(比值比=0.168,3.922,9.250,1.030,95%可信区间为0.036~0.789,1.031~14.919,1.036~82.602,1.001~1.059,P<0.05)。结论胃癌根治术后B级胰瘘发生率较低,腹腔镜辅助手术、联合脏器切除、使用LigaSure+超声刀、淋巴结清扫数目是胃癌根治术后B级胰瘘发生的独立影响因素。临床试验注册:在美国ClinicalTrial.gov注册,注册号:NCT03391687。

Objective To investigate the incidence of postoperative pancreatic fistula(POPF)and its risk factors after radical gastrectomy.Methods The prospective study was conducted.The clinicopathological data of 2089 patients who underwent radical gastrectomy in 22 medical centers between December 2017 and November 2018 were collected,including 380 in the Zhongshan Hospital of Fudan University,351 in the Renji Hospital of Shanghai Jiaotong University School of Medicine,130 in the Ruijin Hospital of Shanghai Jiaotong University School of Medicine,139 in the Peking University Cancer Hospital,128 in the Fujian Provincial Cancer Hospital,114 in the First Hospital Affiliated to Army Medical University,104 in the First Affiliated Hospital of Nanchang University,104 in the Affiliated Hospital of Qinghai University,103 in the Weifang People′s Hospital,102 in the Fujian Medical University Union Hospital,99 in the First Affiliated Hospital of Air Force Medical University,97 in the Sir Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine,60 in the Hangzhou First People′s Hospital Affiliated to Zhejiang University School of Medicine,48 in the Fudan University Shanghai Cancer Center,29 in the First Affiliated Hospital of Xi′an Jiaotong University,26 in the Lishui Municipal Central Hospital,26 in the Guangdong Provincial People′s Hospital,23 in the Jiangsu Province Hospital,13 in the First Affiliated Hospital of Sun Yat-Sen University,7 in the Second Hospital of Jilin University,4 in the First Affiliated Hospital of Xinjiang Medical University,2 in the Beijing Chao-Yang Hospital of Capital Medical University.Observation indicators:(1)the incidence of POPF after radical gastrectomy;(2)treatment of grade B POPF after radical gastrectomy;(3)analysis of clinicopathological data;(4)analysis of surgical data;(5)risk factors for grade B POPF after radical gastrectomy.Measurement data with normal distribution were represented as Mean±SD,and comparison between groups was analyzed using ANOVA.Count data were described as absolute numbers or percentages,and comparison between groups was analyzed using the chi-square test.Univariate analysis was conducted using the t test or chi-square test based on data excluding missing data of clinico-pathological and surgical data.Multivariate analysis was conducted using the Logistic regression model based on factors with P<0.20 in univariate analysis.Results There were 2089 patients screened for eligibility,including 1512 males,576 females and 1 without sex information,aged(62±11)years.The body mass index(BMI)was(23±3)kg/m2.(1)The incidence of POPF after radical gastrectomy:the total incidence rate of POPF in the 2089 patients was 20.728%(433/2089).The incidence rates of biochemical fistula,grade B pancreatic fistula,and grade C pancreatic fistula were 19.627%(410/2089),1.101%(23/2089),0,respectively.(2)Treatment of grade B POPF after radical gastrectomy:2 of 23 patients with grade B POPF after radical gastrectomy had drainage tube placed for more than 21 days and received anti-infective therapy.Four of 23 patients with grade B POPF after radical gastrectomy had ascites detected by imaging examination,of which 2 received peritoneal drainage guided by ultrasound,1 received failed puncture drainage,1 received no puncture drainage,and they were given anti-infective therapy.Eleven of 23 patients with grade B POPF after radical gastrectomy had no ascites detected by imaging examinations,and they were given anti-infective therapy and inhibitors of pancreas secretion for clinical manifestation as fever or elevated white blood cells.Six patients with no typical clinical manifestations were given somatostatin to inhibite pancreas secretion and prolonged duration of abdominal drainage tube placement(with a median time of 7 days).All the 23 patients recovered well after treatment,without reoperation.(3)Analysis of clinicopathological data:for the 2089 patients,BMI,cases with or without neoadjuvant therapy were(23±3)kg/m2,1487,160 of patients without pancreatic fistula,(23±3)kg/m2,386,22 of patients with biochemical fistula,and(24±3)kg/m2,22,1 of patents with grade B pancreatic fistula,showing significant differences between the three groups(F=5.787,χ2=8.269,P<0.05).(4)Analysis of surgical data:for the 2089 patients,cases with open surgery,laparoscopic assisted surgery,totally laparoscopic surgery(surgical method),cases with D1 lymph lode dissection,D2 lymph lode dissection,and other lymph lode dissection(range of lymph lode dissection),cases with no omentectomy,partial omentectomy,and total omentectomy(range of omentectomy),cases with no usage of energy facility,usage of CUSA,LigaSure,LigaSure+CUSA as energy facility,cases with or without biological glue,the number of lymph node dissection were 737,624,292,24,1580,51,418,834,381,63,1530,23,16,1431,201,33±14 of patients without pancreatic fistula,146,189,74,11,389,9,110,171,128,35,359,6,9,378,31,31±14 of patients with biochemical fistula,and 14,5,4,0,20,3,6,13,4,2,18,1,2,22,1,37±16 of patients with grade B pancreatic fistula,showing significant differences between the three groups(χ2=15.578,9.397,15.023,28.245,8.359,F=4.945,P<0.05).(5)Risk factors for grade B POPF after radical gastrectomy:results of univariate analysis showed that usage of energy facility was a related factor for grade B POPF after radical gastrectomy(χ2=9.914,P<0.05).Results of multivariate analysis showed that laparoscopic assisted surgery,combined evisceration,application of LigaSure+CUSA,the number of lymph lode dissection were independent factors for for grade B POPF after radical gastrectomy(odds ratio=0.168,3.922,9.250,1.030,95%confidence interval:0.036-0.789,1.031-14.919,1.036-82.602,1.001-1.059,P<0.05).Conclusions The incidence of grade B POPF after radical gastrectomy is relatively low.Laparoscopic assisted surgery,combined evisceration,application of LigaSure+CUSA,and the number of lymph lode dissection are independent risk factors for grade B POPF.Trial Registration:This study was registrated at ClinicalTrial.gov in United States with the registration number of NCT03391687.