局部进展期胃腺癌患者接受根治性切除术联合紫杉醇腹腔热灌注化疗的安全性研究

Safety of patients undergoing radical resection combined with paclitaxel-based hyperthermic intraperitoneal chemotherapy for locally advanced gastric cancer

目的探究局部进展期胃癌患者接受根治性切除术联合紫杉醇腹腔热灌注化疗(HIPEC)的安全性。方法本研究为回顾性队列研究,收集2019年7月至2021年4月期间于四川大学华西医院胃肠外科收治的467例局部进展期胃腺癌患者的临床病理资料,其中根治切除术+紫杉醇HIPEC 151例(手术+HIPEC组),仅接受根治性切除术316例(单纯手术组)。按照美国卫生与公众服务部公布的常见不良事件评价标准(CTCAE 5.0)对纳入患者的围手术期不良反应事件的发生情况进行评价。根据腹腔热灌注化疗次数对HIPEC组患者进行亚组分析,通过χ^(2)检验对不同亚组的不良事件发生率进行差异分析。并通过logistic模型分析局部进展期胃腺癌患者接受根治性切除术联合紫杉醇HIPEC发生不良事件的独立危险因素。结果手术+HIPEC组中,男性113例(74.8%),女性38例(25.2%);中位年龄为64(55,68)岁;术后接受1次、2次和3次紫杉醇HIPEC的患者分别有18例(11.9%)、79例(52.3%)和54例(35.8%),中位肿瘤最大径为5.0(3.6,6.5)cm。单纯手术组中,男性244例(77.2%),女性72例(22.8%);中位年龄为63(54,68)岁,中位肿瘤最大径为4.0(3.0,5.5)cm。手术+HIPEC组中,共有112例(74.2%)患者在围手术期内出现了198例次2级及以上不良事件,其中以术后低白蛋白血症的发生次数最多(85例,56.3%),其次是术后贫血(50例,33.1%)。与单纯手术组相比,手术+HIPEC组患者中术后低白蛋白血症[56.3%(85/151)比37.7%(119/316),χ^(2)=14.420,P<0.001]、贫血[33.1%(50/151)比22.5%(71/316),χ^(2)=6.030,P=0.014]、术后腹痛[7.3%(11/151)比1.6%(5/316),χ^(2)=10.042,P=0.002]和术后腹胀[5.3%(8/151)比1.3%(4/316),χ^(2)=5.123,P=0.024]的发生率均更高,差异均有统计学意义。HIPEC 1次、2次与3次组的术后低白蛋白血症[13/18比67.1%(53/79)比35.2%(19/54),χ^(2)=12.955,P<0.001]和肺部感染发生率[6/18比6.3%(5/79)比1.9%(1/54),χ^(2)=13.232,P<0.001]比较,差异均有统计学意义。单因素分析结果显示,体质指数、肿瘤Borrmann分型和HIPEC次数与手术+HIPEC组围手术期不良事件发生有关(均P<0.05)。但多因素logistic分析后,并未发现上述因素是手术+HIPEC组围手术期不良事件发生的独立危险因素(均P>0.05)。结论根治性切除术后行紫杉醇HIPEC会增加局部进展期胃癌患者术后低白蛋白血症、贫血以及术后腹痛腹胀的发生风险,但增加HIPEC次数并未显著升高其相关不良事件的发生风险。本研究未发现紫杉醇HIPEC相关不良事件的独立危险因素。

Objective To analyze the safety of paclitaxel-based,hyperthermic,intraperitoneal perfusion chemotherapy(HIPEC)after radical resection of locally advanced gastric cancer.Methods This was a retrospective cohort study of clinicopathological data of 467 patients with locally advanced gastric adenocarcinoma who had been admitted to the Department of Gastrointestinal Surgery,West China Hospital,Sichuan University between July 2019 and April 2021.Among these patients,151 had undergone radical resection combined with post-operative paclitaxel-based HIPEC(surgery+HIPEC group)and 316 radical resection alone(surgery group).The adverse perioperative events in study patients were evaluated according to the Common Terminology Criteria for Adverse Events(CTCAE 5.0)published by the U.S.Department of Health and Human Services.Subgroup analysis was performed on patients in the surgery+HIPEC group according to the number of times HIPEC was administered and the incidence of adverse events was compared between subgroups using theχ^(2)test.Independent risk factors for paclitaxel-based HIPEC-associated adverse events were identified by applying a logistic model.Results In the surgery+HIPEC group,there were 113(74.8%)male and 38(25.2%)female patients of median age 64(55,68)years,18(11.9%),79(52.3%),and 54(35.8%)of whom had undergone one,two,and three paclitaxel-based HIPEC treatments,respectively,after surgery.The median maximum tumor diameter was 5.0(3.6,6.5)cm.In the surgery group,there were 244(77.2%)male and 72(22.8%)female patients of median age 63(54,68)and the median maximum tumor diameter was 4.0(3.0,5.5)cm.In the surgery+HIPEC group,112 patients(74.2%)had 198 Grade 2 or higher adverse perioperative events,postoperative hypoalbuminemia being the commonest(85 cases,56.3%),followed by postoperative anemia(50 cases,33.1%).Compared with the surgery group,the incidences of postoperative hypoalbuminemia(56.3%[85/151]vs.37.7%[119/316],χ^(2)=14.420,P<0.001),anemia(33.1%[50/151]vs.22.5%[71/316],χ^(2)=6.030,P=0.014),abdominal pain(7.3%[11/151]vs.1.6%[5/316],χ^(2)=10.042,P=0.002)and abdominal distension(5.3%[8/151]vs.1.3%[4/316],χ^(2)=5.123,P=0.024)were all significantly higher in the surgery+HIPEC group.Analysis of the three HIPEC subgroups revealed significant differences in the incidences of postoperative hypoalbuminemia(13/18 vs.67.1%[53/79]vs.35.2%[19/54],χ^(2)=12.955,P<0.001)and pulmonary infection(6/18 vs.6.3%[5/79]vs.1.9%[1/54],χ^(2)=13.232,P<0.001)between them.Univariate analysis identified body mass index,Borrmann's type and number of HIPEC treatments as associated with perioperative adverse events in the surgery+HIPEC group(P<0.05).However,according to multifactorial logistic analysis,the above factors were not independent risk factors for perioperative adverse events in the surgery+HIPEC group(P>0.05).Conclusions Paclitaxel-based HIPEC after radical resection significantly increases the risk of postoperative hypoalbuminemia,anemia,abdominal pain,and abdominal distension in patients who have undergone excision of locally advanced gastric cancer.However,increasing the frequency of HIPEC treatments did not significantly increase the risk of paclitaxel-based HIPEC-related adverse events.Moreover,univariate and multivariate analysis did not identify any independent risk factors for paclitaxel HIPEC-related adverse events.