意外胆囊癌病人预后列线图模型的构建

doi:10.16139/j.1007-9610.2024.01.07

摘要/Abstract

摘要：

目的：构建并验证可有效预测意外胆囊癌(incidental gallbladder cancer，IGBC)病人预后的列线图模型。方法：回顾性分析2011年5月至2022年10月西安交通大学第一附属医院收治的161例因IGBC而需根治手术病人的临床资料。使用COX比例风险回归模型筛选影响IGBC总体生存(OS)的影响因素。根据IGBC病人预后的独立影响因素构建列线图模型。利用一致性指数(concordance index, C-index)和校准曲线来验证模型的性能。利用受试者工作特征（receiver operating characteristic, ROC）曲线分析和决策曲线分析（decision curve analysis, DCA）来验证所绘制的列线图的预测精准度和净收益。结果：单因素COX回归分析提示，年龄、T分期、N分期、M分期、术前癌胚抗原(CEA)、术前糖类抗原(CA)19-9、术前红细胞体积分布宽度变异系数（RDW-CV）、治疗方式、复发转移是影响IGBC病人根治术后远期生存的危险因素。多因素COX回归分析提示，T分期、N分期、术前CA19-9、术前RDW-CV、术前天冬氨酸转氨酶(AST)、治疗方式、复发转移是影响IGBC病人预后的独立危险因素。所构建的列线图模型C-index为0.872。校准图显示列线图的良好性能。ROC曲线下面积为0.869，证实列线图的高精准度。DCA证实列线图模型的高净获益。结论：构建的列线图模型可准确、直观地预测IGBC病人根治术后生存概率。

关键词: 意外胆囊癌, 临床预测模型, 预后分析, 列线图

Abstract:

Objective To construct and validate an effective prognostic nomogram for the patients with incidental gallbladder cancer(IGBC). Methods The clinical data of 161 patients with IGBC requiring radical surgery admitted to the First Affiliated Hospital of Xi’an Jiaotong University from May 2011 to October 2022 was analyzed retrospectively. COX proportional risk regression model was used to screen for influencing factors on overall survival(OS) of IGBC. Nomogram was constructed based on independent influencing factors that affected the prognosis of IGBC patients. The concordance index(C-index) and calibration curve were used to validate the performance of the model. Receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) were used to validate the predictive accuracy and net benefit of the plotted column chart. Results Univariate COX regression analysis suggested that age, T stage, N stage, M stage, preoperative carcinoembryonic antigen(CEA), preoperative carbohydrate antigen19-9(CA19-9), preoperative red blood cell volume distribution on width coefficient of variation(RDW-CV), treatment method, and recurrence and metastasis were risk factors which affected the long-term survival of IGBC patients after radical surgery. Multivariate COX regression analysis suggested that T stage, N stage, preoperative CA19-9， preoperative RDW-CV, preoperative AST， treatment methods, and recurrence and metastasis were independent risk factors which affected the prognosis of IGBC patients. The C-index of the constructed prognostic model was 0.872. The calibration plot demonstrated good performance of the Nomogram. ROC curve analysis showed an area under the curve of 0.869, confirming a high sensitivity and specificity. A high net benefit was proven by DCA. Conclusions The constructed Nomogram can accurately and intuitively predict the survival probability of IGBC patients after radical surgery.

Key words: Incidental gallbladder cancer, Clinical prediction model, Prognosis, Nomogram

中图分类号:

R735.8

莫建涛, 曹瑞奇, 任加强, 耿智敏, 仵正, 程亚丽. 意外胆囊癌病人预后列线图模型的构建[J]. 外科理论与实践, 2024, 29(01): 40-45.

MO Jiantao, CAO Ruiqi, REN Jiaqiang, GENG Zhimin, WU Zheng, CHENG Yali. Construction of a prognostic Nomogram for patients with incidental gallbladder cancer[J]. Journal of Surgery Concepts & Practice, 2024, 29(01): 40-45.

图/表 5

表1

图1

图2

图3

图4

参考文献 27

[1]	孙旭恒, 任泰, 耿亚军, 等. 中国胆囊癌外科治疗现状与病理学特征多中心回顾性研究(附4345例报告)[J]. 中国实用外科杂志, 2021, 41(1):99-106.
	SUN X H, REN T, GENG Y J, et al. A large scale multicenter retrospective study of current surgical treatment modalities and pathological characteristics of patients with gallbladder cancer in China:a report of 4,345 cases[J]. Chin J Pract Surg, 2021, 41(1):99-106.
[2]	ROA J C, GARCIA P, KAPOOR V K, et al. Gallbladder cancer[J]. Nat Rev Dis Primers, 2022, 8(1):69. doi: 10.1038/s41572-022-00398-y pmid: 36302789
[3]	周迪, 全志伟. “意外胆囊癌”更名与重视胆囊良性疾病的规范化诊治[J]. 肝胆胰外科杂志, 2020, 32(11):641-645.
	ZHOU D, QUAN Z W. Renaming "incidental gallbladder cancer" and revisiting the standardised management of benign gallbladder disease[J]. J Hepatopancreatobiliary Surg, 2020, 32(11):641-645.
[4]	CAVALLARO A, PICCOLO G, DI VITA M, et al. Mana-ging the incidentally detected gallbladder cancer: algorithms and controversies[J]. Int J Surg, 2014, 12(Suppl 2):S108-S119.
[5]	DE SAVORNIN LOHMAN E A J, DE BITTER T J J, HANNINK G, et al. Development and external validation of a model to predict overall survival in patients with resected gallbladder cancer[J]. Ann Surg, 2023, 277(4):e856-e863.
[6]	WU Y, LI Q, CAI Z, et al. Survival prediction for gallbladder carcinoma after curative resection: comparison of nomogram and Bayesian network models[J]. Eur J Surg Oncol, 2020, 46(11):2106-2113. doi: 10.1016/j.ejso.2020.07.009 pmid: 32807616
[7]	BENSON A B, D'ANGELICA M I, ABBOTT D E, et al. Hepatobiliary Cancers, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology[J]. J Natl Compr Canc Netw, 2021, 19(5):541-565.
[8]	XIE Z H, SHI X, LIU M Q, et al. Development and validation of a nomogram to predict overall survival in patients with incidental gallbladder cancer: a retrospective cohort study[J]. Front Oncol, 2023,12:1007374.
[9]	LUNDGREN L, MUSZYNSKA C, ROS A, et al. Management of incidental gallbladder cancer in a national cohort[J]. Br J Surg, 2019, 106(9):1216-1227. doi: 10.1002/bjs.11205 pmid: 31259388
[10]	ADDEO P, CENTONZE L, LOCICERO A, et al. Incidental gallbladder carcinoma discovered after laparoscopic cholecystectomy: identifying patients who will benefit from reoperation[J]. J Gastrointest Surg, 2018, 22(4):606-614. doi: 10.1007/s11605-017-3655-z pmid: 29274001
[11]	SACHAN A, SALUJA S S, NEKARAKANTI P K, et al. Raised CA19-9 and CEA have prognostic relevance in gallbladder carcinoma[J]. BMC Cancer, 2020, 20(1):826. doi: 10.1186/s12885-020-07334-x pmid: 32867709
[12]	CHEN Z, LIU Z, ZHANG Y, et al. Combination of CA19-9 and the neutrophil-to-lymphocyte ratio for the differential diagnosis of gallbladder carcinoma[J]. Cancer Manag Res, 2020,12:4475-4482.
[13]	BAI Y, LIU Z S, XIONG J P, et al. Nomogram to predict overall survival after gallbladder cancer resection in China[J]. World J Gastroenterol, 2018, 24(45):5167-5178.
[14]	WU J, YANG Y, CHENG L, et al. GCdiscrimination: identification of gastric cancer based on a milliliter of blood[J]. Brief Bioinform, 2021, 22(1):536-544. doi: 10.1093/bib/bbaa006 pmid: 32010933
[15]	D'HONDT M, LAPOINTE R, BENAMIRA Z, et al. Carcinoma of the gallbladder: patterns of presentation, prognostic factors and survival rate. An 11-year single centre experience[J]. Eur J Surg Oncol, 2013, 39(6):548-553. doi: 10.1016/j.ejso.2013.02.010 pmid: 23522952
[16]	章正威, 王翔, 章应峰, 等. 意外胆囊癌组织中糖类抗原19-9和癌胚抗原表达的预后价值[J]. 黑龙江医学, 2023, 47(4):389-392.
	ZHANG Z W, WANG X, ZHANG Y F, et al. Prognostic value of carbohydrate antigen19-9 and carcinoma embryonic antigen expression in unexpected gallbladder carcinoma tissues[J]. Heilongjiang Med J, 2023, 47(4):389-392.
[17]	WANG X, YU Y, TAO Y, et al. Clinical-radiological characteristic for predicting ultra-early recurrence after liver resection in solitary hepatocellular carcinoma patients[J]. J Hepatocell Carcinoma, 2023,10:2323-2335.
[18]	ZHAO H, WU L, YAN G, et al. Inflammation and tumor progression: signaling pathways and targeted intervention[J]. Signal Transduct Target Ther, 2021, 6(1):263.
[19]	AI L, MU S, HU Y. Prognostic role of RDW in hematological malignancies: a systematic review and meta-analysis[J]. Cancer Cell Int, 2018,18:61.
[20]	龙云祥, 曲凯, 张靖垚, 等. 肝细胞癌术前红细胞分布宽度的预后价值[J]. 中华消化外科杂志, 2021, 20(2):205-212.
	LONG Y X, QU K, ZHANG J Y. Prognostic value of preoperative red blood cell distribution width for hepatocellular carcinoma[J]. Chin J Dig Surg, 2021, 20(2):205-212.
[21]	LEI K, DENG Z, WANG J, et al. A novel nomogram based on the hematological prognosis risk scoring system can predict the overall survival of patients with hepatocellular carcinoma[J]. J Cancer Res Clin Oncol, 2023, 149(16):14631-14640. doi: 10.1007/s00432-023-05255-3 pmid: 37584710
[22]	ŁOCHOWSKI M, ŁOCHOWSKA B, CHAŁUBIŃSKA-FENDLER J, et al. Prognostic factors determining survival of patients operated for non-small cell lung cancer with consideration given to morphological parameters of blood[J]. Cancer Manag Res, 2021,13:479-487.
[23]	LI Y, WU H, XING C, et al. Prognostic evaluation of colorectal cancer using three new comprehensive indexes related to infection, anemia and coagulation derived from peripheral blood[J]. J Cancer, 2020, 11(13):3834-3845. doi: 10.7150/jca.42409 pmid: 32328188
[24]	LI Y, XING C, WEI M, et al. Combining red blood cell distribution width (RDW-CV) and CEA predict poor prognosis for survival outcomes in colorectal cancer[J]. J Cancer, 2019, 10(5):1162-1170. doi: 10.7150/jca.29018 pmid: 30854125
[25]	BENSON A B, D'ANGELICA M I, ABBOTT D E, et al. Guidelines insights: hepatobiliary cancers, version 2.2019[J]. J Natl Compr Canc Netw, 2019, 17(4):302-310.
[26]	耿智敏, 汤朝晖. 2018年NCCN指南更新版胆囊癌诊治进展述评[J]. 西部医学, 2018, 30(7):937-942,947.
	GENG Z M, TANG Z H. The development on diagnosis and management of gallbladder cancer:focus on the update of NCCN guideline in 2018[J]. Med J West China, 2018, 30(7):937-942,947.
[27]	BUTTE J M, GÖNEN M, ALLEN P J, et al. The role of laparoscopic staging in patients with incidental gallbladder cancer[J]. HPB (Oxford), 2011, 13(7):463-472.

Variable	Univariate Cox regression analysis		Multivariate Cox regression analysis
Variable	HR(95% CI)	P value	HR(95% CI)	P value
Gender(female vs. male)	1.40 (0.69-2.80)	0.360
Age(>60 vs. ≤60)（year）	1.90 (1.00-3.30)	0.038
Pathological type（other vs. adenocarcinoma）	1.20 (0.28-4.80)	0.830
T(T3+T4 vs. T1+T2)	3.70 (1.40-9.70)	0.007	3.10(1.05-9.16)	0.041
N(N1+N2 vs. N0)	6.3 0(3.00-13.00)	0.000	3.62(1.29-10.22)	0.015
M(M1 vs. M0)	13.00 (5.00-34.00)	0.000
Preoperative AFP(>25 vs. ≤25)(μg/L)	1.80 (0.24-13.00)	0.57
Preoperative CEA(>5 vs. ≤5)(μg/L)	5.10 (2.10-13.00)	0.000
Preoperative CA12-5(>35 vs. ≤35)(μg/L)	1.80 (0.93-3.50)	0.079
Preoperative CA19-9(>37 vs. ≤37)(μg/L)	6.30 (3.10-12.00)	0.000	15.42(4.75-50.00)	0.000
Preoperative RDW-CV(>14.5 vs. ≤14.5)	3.00(1.10-8.70)	0.038	3.15(1.04-9.55)	0.043
Preoperative RDW-SD(>56 vs. ≤56)（fl）	0.00(0-Inf)	1.000
Preoperative ALT(>40 vs. ≤40)(U/L)	1.40 (0.78-2.60)	0.250
Preoperative AST(>40 vs. ≤40)(U/L)	1.80 (0.94-3.50)	0.077	0.27(0.08-0.85)	0.025
Preoperative total bilirubin (>17.1 vs. ≤17.1) (μmol/L)	1.60 (0.80-3.10)	0.190
Preoperative direct bilirubin (>6.8 vs. ≤6.8) (μmol/L)	1.90 (0.99-3.70)	0.055
Preoperative total protein (>60 vs. ≤60)(g/L)	0.94 (0.46-1.90)	0.850
Therapy (palliative operation vs. radical operation)	8.30 (4.50-15.00)	0.000	3.35(1.26-8.89)	0.015
Postoperative drainage（Yes vs. No）	1.00(0.47-2.30)	0.910
Recurrence and metastasis(Yes vs. No)	5.50 (3.10-9.80)	0.000	4.51(2.08-9.79)	0.000
Intraoperative bleeding volume (≤500 vs.>500)(mL)	0.00(0-Inf)	1.000
Common bile duct diameter (≤1 vs. >1)(cm)	0.84 (0.23-3.00)	0.790
Hepatectomy method (other vs. S4b+S5)	0.92 (0.43-2.00)	0.820