高原地区内镜微创保胆取石术后结石复发新型预测列线图的构建和验证

梅学鹏; 陈小彬; 皮世政; 陈屹冲; 星军华; 王海久; 高帅; 周瀛

doi:10.3969/j.issn.1001-5256.2021.03.028

高原地区内镜微创保胆取石术后结石复发新型预测列线图的构建和验证

DOI: 10.3969/j.issn.1001-5256.2021.03.028

梅学鹏^{1, 2},
陈小彬^{1, 2},
皮世政^{1, 2},
陈屹冲^{1, 2},
星军华³,
王海久^{1, 2},
高帅^{1, 2},
周瀛^{1, 2, ,}

1.
青海大学附属医院肝胆胰外科, 西宁 810000
2.
青海省包虫病研究重点实验室, 西宁 810000
3.
青海省仁济医院普外科, 西宁 810000

基金项目:

2017国家重点研发计划“精准医学研究”专项 (2017YFC0909900);

青海省科技厅项目 (2020-ZJ-Y01)

利益冲突声明：本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突，特此声明。

作者贡献声明：梅学鹏、陈小彬负责课题设计、资料分析及撰写论文；梅学鹏、陈小彬参与收集数据及修改论文；皮世政、陈屹冲、星军华、王海久、高帅负责拟定写作思路；周瀛指导撰写文章并最后定稿。

详细信息

作者简介:
梅学鹏(1993—)，男，主要从事肝包虫病、肝胆胰疾病临床研究

陈小彬(1992—)，男，主要从事肝胆胰肿瘤性疾病临床研究

通信作者:
周瀛，17697227511@163.com

二者对本文贡献相同，同为第一作者

中图分类号: R657.42
计量
- 文章访问数: 419
- HTML全文浏览量: 138
- PDF下载量: 31
- 被引次数: 0
出版历程
- 收稿日期: 2020-08-31
- 录用日期: 2020-11-02
- 出版日期: 2021-03-20

Construction and verification of a new nomogram for predicting stone recurrence after endoscopic minimally invasive gallbladder-preserving cholecystolithotomy at high altitude

Xuepeng MEI^{1, 2},
Xiaobin CHEN^{1, 2},
Shizheng PI^{1, 2},
Yichong CHEN^{1, 2},
Junhua XING³,
Haijiu WANG^{1, 2},
Shuai GAO^{1, 2},
Ying ZHOU^{1, 2
, ,}

1.
Department of Hepatopancreatobiliary Surgery, Qinghai University Affiliated Hospital, Xining 810000, China
2.
Qinghai Province Key Laboratory of Hydatid Disease Research, Xining 810000, China
3.
Department of General Surgery, Renji Hospital of Qinghai Province, Xining 810000, China

摘要

摘要: 目的对内镜微创保胆取石术后结石复发相关因素进行分析，根据独立危险因素，建立预测术后结石复发风险的列线图模型。方法回顾性分析2012年1月—2018年1月在青海大学附属医院接受内镜微创保胆取石术的144例胆囊结石患者的临床资料。根据术后结石复发情况将患者分为无复发组(n=130)和复发组(n=14)。两组间计数资料比较采用χ²检验。通过LASSO和logistic回归分析评价患者术后结石复发的独立风险因素，根据回归系数绘制相应的列线图预测模型。通过绘制校准曲线评估预测列线图的可靠性；采用Harrell一致性指数以量化预测列线图的判别性能；通过受试者工作特征曲线来评估该预测模型的灵敏度、特异度，计算曲线下面积(AUC)。结果 144例患者内镜微创保胆取石术手术均获得成功，其中14例(9.7%)术后复发结石。通过多因素分析确定了4个影响复发的独立危险因素，分别为家族史(OR=3.245，95%CI：0.752~13.567，P=0.104)、饮食的规律性(OR=3.752，95%CI：1.067~14.141，P=0.041)、结石的均一性(OR=5.871，95%CI：1.636~25.390，P=0.010)和药物依从性(OR=0.225，95%CI：0.057~0.799，P=0.024)。列线图模型在建模样本中的一致性系数(C-index)为0.835(95%CI：0.732~0.938)，在验证样本中的C-index为0.792 5，说明本研究列线图模型具有良好的精准度和区分度。预测列线图的AUC值为0.835，表明该列线图预测价值较高。结论家族史、饮食的规律性、胆结石的均一性和药物依从性是内镜微创保胆取石术后结石复发的独立危险因素，根据上述独立危险因素建立的列线图有助于预测术后结石复发的风险。
- 胆囊结石病 /
- 复发 /
- 列线图
Abstract: Objective To investigate related factors for stone recurrence after endoscopic minimally invasive gallbladder-preserving cholecystolithotomy, and to establish a nomogram model for predicting the risk of stone recurrence after surgery based on independent risk factors. Methods A retrospective analysis was performed for the clinical data of 144 patients with gallstones who underwent endoscopic minimally invasive gallbladder-preserving cholecystolithotomy in Qinghai University Affiliated Hospital from January 2012 to January 2018, and according to postoperative stone recurrence, the patients were divided into non-recurrence group and recurrence group. The chi-square test was used for comparison of categorical data between two groups. LASSO and logistic regression analyses were used to analyze independent risk factors for postoperative stone recurrence, and the corresponding nomogram prediction model was plotted according to regression coefficient. The calibration curve was plotted to evaluate the reliability of the predictive nomogram; Harrell consistency index was used to quantify the discriminatory performance of the predictive nomogram; the receiver operating characteristic (ROC) curve was used to evaluate the sensitivity, specificity, and area under the ROC curve (AUC) of this predictive nomogram. Results All 144 patients underwent successful endoscopic minimally invasive gallbladder-preserving cholecystolithotomy, among whom 14 patients (9.7%) experienced stone recurrence after surgery. The multivariate analysis showed that family history (odds ratio [OR]= 3.245, 95% confidence interval [CI]: 0.752-13.567, P=0.104), regular diet (OR=3.752, 95% CI: 1.067-14.141, P=0.041), stone homogeneity (OR=5.871, 95% CI: 1.636-25.390, P=0.010), and medication compliance (OR=0.225, 95% CI: 0.057-0.799, P=0.024) were independent risk factors for recurrence. The nomogram model had an index of concordance (C-index) of 0.835 (95% CI: 0.732-0.938) in the modeling sample and 0.7925 in the verification sample, suggesting that the nomogram model in this study had good accuracy and discrimination. The predictive nomogram had an AUC of 0.835, suggesting that this nomogram had a relatively high predictive value. Conclusion Family history, regular diet, stone homogeneity, and medication compliance are independent risk factors for stone recurrence after endoscopic minimally invasive gallbladder-preserving cholecystolithotomy, and the nomogram constructed based on these independent risk factors may help to predict the risk of postoperative stone recurrence.
- Cholecystolithiasis /
- Recurrence /
- Nomograms

HTML全文

图 1 采用LASSO进行人口学和临床特征选择

注：a，LASSO模型中的最佳λ值通过选择最低标准进行交叉验证。绘制了部分似然偏差(二项式偏差)曲线与对数(λ)的关系曲线。通过执行最小标准和最小标准的1个标准误，虚线垂直线显示为最佳值。b，15个特征因素的LASSO系数分布。根据对数(λ)序列对系数剖面图进行了评价。垂直线显示在使用交叉验证选择的值，其中最佳λ产生了4个具有非零系数的特征。

下载: 全尺寸图片幻灯片

图 2 内镜微创保胆取石术后复发列线图

注：a，在队列中建立了复发风险列线图，包括家族史、饮食规律、胆结石的均匀一性和药物依从性。b，使用列线图时，在每个变量轴上显示单个患者的值，向上绘制出一条垂直线，以找到每个变量值收到的点数。在总点轴上给出了这些变量值的总和，并向下绘制了一条垂直线，以求3年或5年无复发的概率。

下载: 全尺寸图片幻灯片

图 3 复发风险预测图的校准曲线、ROC曲线及决策曲线

注：a, 队列中复发风险列线图预测的校准曲线，x轴显示了预测的复发风险，y轴显示术后明确诊断复发。实线表示列线图的性能，越接近对角线虚线则表示越好的预测能力。b, ROC曲线用以验证模型的预测能力。c, 复发风险列线图的决策曲线分析。y轴测量净获益，深蓝折线显示复发风险列线图，浅蓝斜线则显示所有患者均为复发，黑色横线为假设无患者复发。该决策曲线表明，如果患者和医生的阈值概率分别为1和76%，在此范围内，复发列线图净获益值较高，临床预测效用良好。

下载: 全尺寸图片幻灯片

表 1 无复发组和复发组患者的基线特征

指标	无复发(n=130)	复发(n=14)	合计(n=144)	χ²值	P值
年龄[例(%)]				2.695	0.747
≤20岁	10(7.69)	2(14.29)	12(8.33)
21~30岁	27(20.77)	3(21.43)	30(20.83)
31~40岁	39(30.00)	3(21.43)	42(29.17)
41~50岁	42(32.31)	6(42.86)	48(33.33)
51~60岁	10(7.69)	0	10(6.95)
＞60岁	2(1.54)	0	2(1.39)
性别[例(%)]				0.106	0.745
女	82(63.08)	10(71.43)	92(63.89)
男	48(36.92)	4(28.57)	52(36.11)
BMI[例(%)]				2.448	0.294
＜24 kg/m²	85(65.38)	9(64.28)	94(65.28)
24~28 kg/m²	33(25.39)	2(14.29)	35(24.30)
≥28 kg/m²	12(9.23)	3(21.43)	15(10.42)
家族史[例(%)]				2.080	0.149
无	109(83.85)	9(64.29)	118(81.94)
有	21(16.15)	5(35.71)	26(18.06)
孕史[例(%)]				1.529	0.676
男性	48(36.92)	4(28.57)	52(36.11)
未孕	26(20.00)	3(21.43)	29(20.14)
孕1	42(32.31)	4(28.57)	46(31.94)
孕≥2	14(10.77)	3(21.43)	17(11.81)
饮食的规律性[例(%)]				8.386	0.004
规律	99(76.15)	5(35.71)	104(72.22)
不规律	31(23.85)	9(64.29)	40(27.78)
胆结石的数量[例(%)]				6.952	0.073
1个	81(62.31)	5(35.71)	86(59.72)
2个	17(13.08)	1(7.14)	18(12.50)
3个	6(4.61)	2(14.29)	8(5.56)
＞3个	26(20.00)	6(42.86)	32(22.22)
结石最大直径[例(%)]				3.857	0.145
＜2 cm	86(66.15)	6(42.86)	92(63.89)
2 cm	33(25.39)	7(50.00)	40(27.78)
≥3 cm	11(8.46)	1(7.14)	12(8.33)
胆结石的均一性[例(%)]				7.906	0.005
均一	91(70.00)	4(28.57)	95(65.97)
不均一	39(30.00)	10(71.43)	49(34.03)
胆囊壁厚度[例(%)]				0.668	0.413
正常	93(71.54)	12(85.71)	105(72.92)
增厚	37(28.46)	2(14.29)	39(27.08)
胆囊黏膜光滑程度[例(%)]				0.000	0.999
光滑	101(77.69)	11(78.57)	112(77.78)
粗糙	29(22.31)	3(21.43)	32(22.22)
胆囊收缩功能[例(%)]				0.163	0.686
＜30%	104(80.00)	10(71.43)	114(79.17)
≥30%	26(20.00)	4(28.57)	30(20.83)
术前TCH[例(%)]				0.045	0.832
＜5.17 mmol/L	113(86.92)	13(92.86)	126(87.50)
≥5.17 mmol/L	17(13.08)	1(7.14)	18(12.50)
术前TG[例(%)]				0.000	0.999
＜1.7 mmol/L	98(75.38)	11(78.57)	109(75.69)
≥1.7 mmol/L	32(24.62)	3(21.43)	35(24.31)
药物依从性[例(%)]				3.872	0.049
不规律	36(27.69)	8(57.14)	44(30.56)
规律	94(72.31)	6(42.86)	100(69.44)

下载: 导出CSV

表 2 内镜微创保胆取石术后复发的危险因素logistic回归结果

截距和变量	β值	OR(95%CI)	P值
截距	-3.114 7	0.044(0.009~0.148)	＜0.001
家族史	1.177 1	3.245(0.752~13.567)	0.104
饮食的规律性	1.322 3	3.752(1.067~14.141)	0.041
胆结石的均一性	1.770 1	5.871(1.636~25.390)	0.010
药物依从性	-1.493 0	0.225(0.057~0.799)	0.024

下载: 导出CSV

参考文献(22)

[1]	HE XY, SHI J. Consensus opinion on medical treatment of chronic cholecystitis and cholecystolithiasis in China (2018)[J]. J Clin Hepatol, 2019, 35(6): 1231-1236. (in Chinese) DOI: 10.3969/j.issn.1001-5256.2015.01.002 何相宜, 施健. 中国慢性胆囊炎、胆囊结石内科诊疗共识意见(2018年)[J]. 临床肝胆病杂志, 2019, 35(6): 1231-1236. DOI: 10.3969/j.issn.1001-5256.2015.01.002
[2]	KERLAN RK, LABERGE JM, RING EJ. Percutaneous cholecystolithotomy: Preliminary experience[J]. J Radiology, 1985, 157(3): 653-656. DOI: 10.1148/radiology.157.3.4059554
[3]	CHESLYN-CURTIS S, RUSSELL RCG. Percutaneous cholecystolithotomy[J]. BMJ Clin Res, 1990, 301(6747): 339-340.
[4]	LIEVENS M, SCHUTZ SM. Percutaneous cholecystolithotomy: Is gall stone recurrence inevitable?[J]. Gastrointest Endosc, 1995, 41(3): 271-272. http://europepmc.org/articles/PMC1374759
[5]	TAN YY, ZHAO G, WANG D, et al. A new strategy of minimally invasive surgery for cholecystolithiasis: Calculi removal and gallbladder preservation[J]. Dig Surg, 2013, 30(4-6): 466-471. DOI: 10.1159/000357823
[6]	GAO DK, WEI SH, LI W, et al. Totally laparoscopic gallbladder-preserving surgery: A minimally invasive and favorable approach for cholelithiasis[J]. Exp Ther Med, 2015, 9(2): 395-398. DOI: 10.3892/etm.2014.2107
[7]	SAUERBREI W, ROYSTON P, BINDER H. Selection of important variables and determination of functional form for continuous predictors in multivariable model building[J]. Stat Med, 2007, 26(30): 5512-5528. DOI: 10.1002/sim.3148
[8]	FRIEDMAN J, HASTIE T, TIBSHIRANI R. Regularization paths for generalized linear models via coordinate descent[J]. J Stat Softw, 2010, 33(1): 1-22. http://neuro-oncology.oxfordjournals.org/external-ref?access_num=20808728&link_type=MED
[9]	KIDD AC, MCGETTRICK M, TSIM S, et al. Survival prediction in mesothelioma using a scalable Lasso regression model: Instructions for use and initial performance using clinical predictors[J]. BMJ Open Respir Res, 2018, 5(1): e000240. DOI: 10.1136/bmjresp-2017-000240
[10]	BALACHANDRAN VP, GONEN M, SMITH JJ, et al. Nomograms in oncology: More than meets the eye[J]. Lancet Oncol, 2015, 16(4): e173-e180. DOI: 10.1016/S1470-2045(14)71116-7
[11]	IASONOS A, SCHRAG D, RAJ GV, et al. How to build and interpret a nomogram for cancer prognosis[J]. J Clin Oncol, 2008, 26(8): 1364-1370. DOI: 10.1200/JCO.2007.12.9791
[12]	KRAMER AA, ZIMMERMAN JE. Assessing the calibration of mortality benchmarks in critical care: The Hosmer-Lemeshow test revisited[J]. Crit Care Med, 2007, 35(9): 2052-2056. DOI: 10.1097/01.CCM.0000275267.64078.B0
[13]	PENCINA MJ, D'AGOSTINO RB. Overall C as a measure of discrimination in survival analysis: Model specific population value and confidence interval estimation[J]. Stat Med, 2004, 23(13): 2109-2123. DOI: 10.1002/sim.1802
[14]	ANDREW JV, ANGEL MC, ELENA BE, et al. Extensions to decision curve analysis, a novel method for evaluating diagnostic tests, prediction models and molecular markers[J]. BMC Medical Informatics and Decision Making, 2008, 8(15): 1039-1052. http://www.bmj.com/lookup/external-ref?access_num=10.1186/1472-6947-8-53&link_type=DOI
[15]	Development and validation of a radiomics nomogram for preoperative prediction of lymph node metastasis in colorectal cancer[J]. Science Foundation in China, 2016, 24(4): 35.
[16]	HAN XM, SHU XC, WANG YP. Research progress on the correlation between cholecystolithiasis, cholecystectomy and gastric cancer[J]. Med Rev, 2020, 26(13): 2559-2563, 2569. (in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-YXZS202013013.htm 韩雪梅, 舒小闯, 王玉平, 等. 胆囊结石及胆囊切除与胃癌相关性研究进展[J]. 医学综述, 2020, 26(13): 2559-2563, 2569. https://www.cnki.com.cn/Article/CJFDTOTAL-YXZS202013013.htm
[17]	WEI L, CHAMPMAN S, LI X, et al. Beliefs about medicines and non-adherence in patients with stroke, diabetes mellitus and rheumatoid arthritis: A cross-sectional study in China[J]. BMJ Open, 2017, 7(10): e017293. DOI: 10.1136/bmjopen-2017-017293
[18]	LI A, LIU JW, ZHANG D. Research progress on recurrence of cholecystolithiasis after endoscopic minimally invasive choledocholithiasis[J]. J Hepatopancreatobiliary Surg, 2019, 31(9): 573-577. (in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-GDYW201909017.htm 李骜, 刘江伟, 张东. 内镜微创保胆取石术后胆囊结石复发的研究进展[J]. 肝胆胰外科杂志, 2019, 31(9): 573-577. https://www.cnki.com.cn/Article/CJFDTOTAL-GDYW201909017.htm
[19]	CONDAT B, ZANDITENAS D, BARBU V, et al. Prevalence of low phospholipid-associated cholelithiasis in young female patients[J]. Dig Liver Dis, 2013, 45(11): 915-919. DOI: 10.1016/j.dld.2013.04.002
[20]	GE HL, WAN H. Analysis of risk factors related to recurrence of gallstones after minimally invasive endoscopic choledocholithotomy[J]. J Binzhou Med Univ, 2016, 39(2): 149-150. (in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-BZYB201602024.htm 葛海龙, 万航. 微创内镜保胆取石术术后胆囊结石复发的相关危险因素分析[J]. 滨州医学院学报, 2016, 39(2): 149-150. https://www.cnki.com.cn/Article/CJFDTOTAL-BZYB201602024.htm
[21]	van de MEEBERG PC, PORTINCASA P, van de HEIJNING BJM, et al. Gallbladder (GB) emptying in vivo and contractility in vitro of gallstone patients on ursodeoxycholic acid(UDCA)[J]. Neth J Med, 1996, 48(1): A39. http://www.sciencedirect.com/science/article/pii/0300297796896458
[22]	LIU T, LI N, LI D, et al. Clinical study on Xiaoshi Lidan capsule combined with ursodeoxycholic acid in the treatment of cholecystolithiasis[J]. China Pharm, 2019, 28(8): 30-32. (in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-YYGZ201908013.htm 刘彤, 李楠, 李栋, 等. 消石利胆胶囊联合熊去氧胆酸治疗胆囊结石临床研究[J]. 中国药业, 2019, 28(8): 30-32. https://www.cnki.com.cn/Article/CJFDTOTAL-YYGZ201908013.htm