[Risk factor analysis on anastomotic leakage after laparoscopic surgery in rectal cancer patient with neoadjuvant therapy and establishment of a nomogram prediction model].

Objective: To investigate the risk factors of anastomotic leakage (AL) after laparoscopic surgery in rectal cancer patient with neoadjuvant therapy and construct a nomogram prediction model. Methods: This study was a retrospective case-control study that collected and reviewed the clinicopathological data of 359 patients who underwent laparoscopic surgery from January 2012 to January 2018, including 202 patients from the Department of General Surgery, Nanfang Hospital of Southern Medical University and 157 patients from the Department of Gastrointestinal Surgery of Fujian Provincial Cancer Hospital. Inclusion criteria: (1) age ≥ 18 years old; (2) diagnosis as rectal cancer by biopsy before treatment; (3) distance from tumor to anus within 12 cm; (4) locally advanced stage (T3-T4 or N+) diagnosed by imaging (CT, MRI, PET or ultrasound); (5) standardized neoadjuvant therapy followed by laparoscopic radical operation. Exclusion criteria: (1) previous history of colorectal cancer surgery; (2) short-term or incomplete standardized neoadjuvant therapy; (3) Miles, Hartmann, emergency surgery, palliative resection; (4) conversion to open surgery. Clinicopathological data, including age, gender, body mass index (BMI), preoperative albumin, distance from tumor to anus, operation hospital, American Society of Anesthesiologists score (ASA score), operation time, T stage, N stage, M stage, TNM stage, pathological complete response (pCR) were analyzed with univariate analysis to identify predictors for AL after laparoscopic surgery in rectal cancer patient with neoadjuvant therapy. Then, incorporated predictors of AL, which were screened by multivariate logistic regression, were plotted by the "rms" package in R software to establish a nomogram model. According to the scale of the nomogram of each risk factor, the total score could be obtained by adding each single score, then the corresponding probability of postoperative AL could be acquired. The area under ROC curve (AUC) was used to evaluate the predictive ability of each risk factor and nomogram on model. AUC > 0.75 indicated that the model had good predictive ability. The Bootstrap method (1000 bootstrapping resamples) was applied as internal verification to show the robustness of the model. The discrimination of the nomogram was determined by calculating the average consistency index (C-index) whose rage was 0.5 to 1.0. Higher C-index indicated better consistency with actual risk. The calibration curve was used to assess the calibration of prediction model. The Hosmer-Lemeshow test yielding a non-significant statistic (P>0.05) suggested no departure from the perfect fit. Results: Of 359 cases, 224 were male, 135 were female, 189 were ≥ 55 years old, 98 had a BMI > 24 kg/m(2), 176 had preoperative albumin ≤ 40 g/L, 128 had distance from tumor to anus ≤ 5 cm, 257 were TNM 0-II stage, 102 were TNM III-IV stage, and 84 achieved pCR after neoadjuvant therapy. The incidence of postoperative AL was 9.5% (34/359). Univariate analysis showed that gender, preoperative albumin and distance from tumor to the anus were associated with postoperative AL (All P<0.05). Multivariate logistic regression analysis revealed that male (OR=2.480, 95% CI: 1.012-6.077, P=0.047), preoperative albumin ≤40 g/L (OR=5.319, 95% CI: 2.106-13.433, P<0.001) and distance from tumor to anus ≤ 5 cm (OR=4.339, 95% CI: 1.990-9.458, P<0.001) were significant independent risk factors for postoperative AL. According to these results, a nomogram prediction model was constructed. The male was for 55 points, the preoperative albumin ≤ 40 g/L was for 100 points, and the distance from tumor to the anus ≤ 5 cm was for 88 points. Adding all the points of each risk factor, the corresponding probability of total score would indicated the morbidity of postoperative AL predicted by this nomogram modal. The AUC of the nomogram was 0.792 (95% CI: 0.729-0.856), and the C-index was 0.792 after internal verification. The calibration curve showed that the predictive results were well correlated with the actual results (P=0.562). Conclusions: Male, preoperative albumin ≤ 40 g/L and distance from tumor to the anus ≤ 5 cm are independent risk factors for AL after laparoscopic surgery in rectal cancer patient with neoadjuvant therapy. The nomogram prediction model is helpful to predict the probability of AL after surgery.目的： 探讨经新辅助治疗后的直肠癌患者腹腔镜术后出现吻合口漏的危险因素并构建列线图预测模型。 方法： 采用回顾性病例对照研究方法，收集2012年1月至2018年1月期间，在南方医科大学南方医院普通外科（202例）和福建省肿瘤医院胃肠肿瘤外科（157例）经新辅助治疗后行腹腔镜手术的359例直肠癌患者的临床病理资料。病例纳入标准：（1）年龄≥18岁；（2）治疗前经肠镜或肛门镜活检确诊为直肠癌；（3）肿瘤距肛门12 cm以内；（4）经CT、MRI、PET或超声肠镜等影像学诊断为局部进展期（T(3~4)或N+）；（5）完成标准化新辅助治疗后行腹腔镜根治性手术治疗。排除标准：（1）既往有结直肠癌手术史；（2）短期或未完成标准化新辅助治疗方案；（3）Miles、Hartmann、急诊手术、姑息性切除；（4）中转开腹。采用单因素分析方法分析年龄、性别、体质指数、术前白蛋白、肿瘤距肛门距离、病例来源单位、美国麻醉医师协会评分、手术时间，以及新辅助治疗后T分期、N分期、M分期、肿瘤TNM分期、病理完全缓解与直肠癌新辅助治疗后腹腔镜微创手术后吻合口漏的关系，进一步用多因素logistic回归分析回归筛选出吻合口漏的独立危险因素，并用R软件中的"rms"软件包完成列线图预测模型的绘制。根据每个危险因素对应列线图上方的标尺，即可得到该因素的单项分数，各单项分数相加得到总分，从总分向下对应，即可获得对应的术后吻合口漏发生概率。通过受试者工作特征（ROC）曲线下面积评估各危险因素及列线图预测模型的预测能力，曲线下面积（AUC）>0.75说明模型具备较好的预测能力。采用Bootstrap法进行内部验证，从原始数据集中随机抽取样本，并进行1 000次重复，通过计算平均一致性指数（C-index）确定模型区分度，C-index范围为0.5~1.0，C-index值越高，表明准确性越高。通过绘制预测结果与实际结果的校正曲线，进行一致性测试。使用Hosmer-Lemeshow检验判断模型的拟合优度，P>0.05表明模型的拟合优度较好。 结果： 本组患者男性224例，女性135例；>55岁者189例；体质指数>24 kg/m(2)者98例；术前白蛋白水平≤40 g/L者176例；肿瘤距肛门≤5 cm者128例；肿瘤TNM分期0~Ⅱ期257例，Ⅲ~Ⅳ期102例；新辅助治疗后病理完全缓解84例。术后吻合口漏发生率为9.5%（34/359）。单因素分析结果显示，性别、术前白蛋白水平以及肿瘤距肛门距离与术后吻合口漏的发生有关（均P<0.05）。多因素logistic回归分析结果显示，男性（OR=2.480，95%CI：1.012~6.077，P=0.047）、术前白蛋白≤40 g/L（OR=5.319，95%CI：2.106~13.433，P<0.001）和肿瘤距肛门≤5 cm（OR=4.339，95%CI：1.990~9.458，P<0.001）是直肠癌患者新辅助治疗后腹腔镜术后发生吻合口漏的独立危险因素（均P<0.05）。根据此结果构建列线图预测模型，性别为男性55分，术前白蛋白≤40 g/L为100分，肿瘤距肛门≤5 cm为88分。通过对每个危险因素单项评分相加，得出的总分对应的概率即为该模型预测的吻合口漏发生概率。列线图预测模型的AUC为0.792（95%CI：0.729~0.856），经内部验证后，模型的C-index值为0.792。校正曲线显示预测结果与实际结果的相关性良好（P=0.562）。 结论： 男性、术前白蛋白≤40 g/L和肿瘤距肛门≤5 cm是直肠癌新辅助治疗后腹腔镜术后吻合口漏的独立危险因素，构建的列线图预测模型有助于预测术后吻合口漏发生的概率。.