Table_3_Development and Validation of a Nomogram for Differentiating Combined Hepatocellular Cholangiocarcinoma From Intrahepatic Cholangiocarcinoma.docx

ObjectivesTo establish a nomogram based on preoperative laboratory study variables using least absolute shrinkage and selection operator (LASSO) regression for differentiating combined hepatocellular cholangiocarcinoma (cHCC) from intrahepatic cholangiocarcinoma (iCCA).
MethodsWe performed a retrospective analysis of iCCA and cHCC patients who underwent liver resection. Blood signatures were established using LASSO regression, and then, the clinical risk factors based on the multivariate logistic regression and blood signatures were combined to establish a nomogram for a differential preoperative diagnosis between iCCA and cHCC. The differential accuracy ability of the nomogram was determined by Harrell’s index (C-index) and decision curve analysis, and the results were validated using a validation set. Furthermore, patients were categorized into two groups according to the optimal cut-off values of the nomogram-based scores, and their survival differences were assessed using Kaplan-Meier curves.
ResultsA total of 587 patients who underwent curative liver resection for iCCA or cHCC between January 2008 and December 2017 at West China Hospital were enrolled in this study. The cHCC score was based on the personalized levels of the seven laboratory study variables. On multivariate logistic analysis, the independent factors for distinguishing cHCC were age, sex, biliary duct stones, and portal hypertension, all of which were incorporated into the nomogram combined with the cHCC-score. The nomogram had a good discriminating capability, with a C-index of 0.796 (95% CI, 0.752–0.840). The calibration plot for distinguishing cHCC from iCCA showed optimal agreement between the nomogram prediction and actual observation in the training and validation sets. The decision curves indicated significant clinical usefulness.
ConclusionThe nomogram showed good accuracy for the differential diagnosis between iCCA and cHCC preoperatively, and therapeutic decisions would improve if it was applied in clinical practice.

研究目的：本研究旨在基于术前实验室检测指标，通过最小绝对收缩和选择算子（least absolute shrinkage and selection operator, LASSO）回归模型，构建列线图（nomogram）以鉴别联合肝细胞胆管细胞癌（combined hepatocellular cholangiocarcinoma, cHCC）与肝内胆管癌（intrahepatic cholangiocarcinoma, iCCA）。
研究方法：本研究对接受肝切除术的iCCA与cHCC患者开展回顾性分析。首先通过LASSO回归构建血液标志物模型，随后结合多因素logistic回归筛选出的临床危险因素与血液标志物模型，构建用于术前鉴别iCCA与cHCC的列线图。采用Harrell一致性指数（C-index）与决策曲线分析评估该列线图的鉴别效能，并通过验证集对结果进行验证。此外，根据列线图评分的最优截断值将患者分为两组，采用Kaplan-Meier曲线评估两组患者的生存差异。
研究结果：本研究纳入2008年1月至2017年12月于华西医院接受根治性肝切除术的587例iCCA或cHCC患者。本研究的cHCC评分基于7项实验室检测指标的个体化水平构建。多因素logistic回归分析显示，区分cHCC与iCCA的独立危险因素包括年龄、性别、胆管结石与门静脉高压，上述因素均与cHCC评分一同被纳入列线图。该列线图具有良好的鉴别效能，C-index为0.796（95%CI：0.752~0.840）。校准曲线显示，在训练集与验证集中，列线图的预测结果与实际观测值均具有极佳的一致性。决策曲线分析表明该列线图具有显著的临床应用价值。
研究结论：本研究所构建的列线图术前鉴别iCCA与cHCC的准确性良好，若将其应用于临床实践，可优化临床治疗决策。