肿瘤细胞减灭术治疗结直肠癌腹膜转移的围手术期安全性及其列线图预测模型构建

Analysis of perioperative efficacy and safety of cytoreductive surgery in the treatment of colorectal cancer peritoneal metastases

目的分析结直肠癌腹膜转移(CRPM)患者实施肿瘤细胞减灭术(CRS)的围手术期安全性及相关影响因素,并构建预测模型。方法采用描述性病例系列研究方法,回顾性收集2019年1月至2021年8月中山大学附属第六医院结直肠外科实施CRS的100例结直肠癌及阑尾黏液腺癌来源的腹膜转移患者临床病理资料和治疗情况(手术时间、器官切除数量、腹膜切除数量、失血量等)。全组男性53例,女性47例;中位年龄52.0(39.0~61.8)岁;同时性腹膜转移患者52例,异时性48例;术前行新辅助治疗患者52例;原发肿瘤位于左半结肠43例,右半结肠28例,直肠14例,阑尾黏液腺癌来源15例。偏态分布的计量资料用M(范围)表示。分析围手术期安全性[围手术期Ⅲ级以上定义为严重不良事件(SAE)],采用单因素和多因素logistic回归分析发生SAE的相关危险因素。对多因素logistic回归分析结果通过R软件绘制列线图预测模型,并用ROC曲线下面积(AUC)和校正曲线评价列线图的效能。结果全组中位腹膜癌指数(PCI)评分为16(1~39)分。68例(68.0%)手术患者达到完整肿瘤减灭程度(肿瘤减灭程度:0~1评分);62例患者在术后进行了腹腔热灌注化疗(HIPEC)治疗。有21例(21.0%)CRPM患者发生了Ⅲ~Ⅳ级SAE共37例次,包括泌尿系统输尿管损伤2例次,围手术期大量出血或贫血6例次,消化系统7例次,呼吸系统15例次,心血管系统4例次,皮肤切口裂开1例次,腹腔感染2例次;未发生Ⅴ级SAE。多因素logistic分析结果显示,癌胚抗原(OR:8.980,95%CI:1.428~56.457,P=0.019)、PCI评分(OR:7.924,95%CI:1.486~42.259,P=0.015)、术中白蛋白输注量(OR:48.959,95%CI:2.115~1133.289,P=0.015)和总输入量(OR:24.729,95%CI:3.956~154.562,P=0.001)是CRS围手术期出现SAE的独立危险因素(均P<0.05)。根据多因素回归模型结果构建CRS围手术期SAE预测列线图,内部验证显示预测列线图的ROC曲线下面积为0.926(95%CI:0.872~0.980),模型Hosmer-Lameshaw检验计算预测效能为95.6%,具有良好的预测准确度和一致性。结论CRS是治疗CRPM的一种安全有效方式。严格筛选病例和围手术期液体管理是降低CRS不良事件发生的重要保证。

Objective To analyzed perioperative safety of cytoreductive surgery(CRS)for patients with colorectal cancer peritoneal metastasis(CRPM)and to construct a predictive model for serious advese events(SAE).Methods A descriptive case-series study was conducted to retrospectively collect the clinicopathological data and treatment status(operation time,number of organ resection,number of peritoneal resection,and blood loss,etc.)of 100 patients with peritoneal metastases from colorectal cancer or appendix mucinous adenocarcinoma who underwent CRS at the Sixth Affiliated Hospital of Sun Yat-sen University from January 2019 to August 2021.There were 53 males and 47 females.The median age was 52.0(39.0-61.8)years old.Fifty-two patients had synchronous peritoneal metastasis and 48 had metachronous peritoneal metastasis.Fifty-two patients received preoperative neoadjuvant therapy.Primary tumor was located in the left colon,the right colon and the rectum in 43,28 and 14 cases,respectively.Fifteen patients had appendix mucinous adenocarcinoma.Measures of skewed distribution are expressed as M(range).Perioperative safety was analyzed,perioperative grade III or higher was defined as SAE.Risk factors associated with the occurrence of SAEs were analyzed using multivariate logistic regression.A nomogram was plotted by R software to predict SAE,the efficacy of which was evaluated using the area under the ROC curve(AUC)and correction curves.Results The median peritoneal cancer index(PCI)score was 16(1-39).Sixty-eight(68.0%)patients achieved complete tumor reduction(tumor reduction score:0-1).Sixty-two patients were treated with intraperitoneal hyperthermic perfusion chemotherapy(HIPEC).Twenty-one(21.0%)patients developed 37 SAEs of grade III-IV,including 2 cases of ureteral injury,6 cases of perioperative massive hemorrhage or anemia,7 cases of digestive system,15 cases of respiratory system,4 cases of cardiovascular system,1 case of skin incision dehiscence,and 2 cases of abdominal infection.No grade V SAE was found.Multivariate logistic regression analysis showed that CEA(OR:8.980,95%CI:1.428-56.457,P=0.019),PCI score(OR:7.924,95%CI:1.486-42.259,P=0.015),intraoperative albumin infusion(OR:48.959,95%CI:2.115-1133.289,P=0.015)and total volume of infusion(OR:24.729,95%CI:3.956-154.562,P=0.001)were independent risk factors for perioperative SAE in CRS(all P<0.05).Based on the result of multivariate regression models,a predictive nomogram was constructed.Internal verification showed that the AUC of the nomogram was 0.926(95%CI:0.872-0.980),indicating good prediction accuracy and consistency.Conclusions CRS is a safe and effective method to treat CRPM.Strict screening of patients and perioperative fluid management are important guarantees for reducing the morbidity of SAE.