胆管癌根治性切除术后患者预后相关因素分析和生存预测模型构建

doi:10.13481/j.1671-587X.20220418

Abstract

Abstract: Objective

To explore the influencing factors of recurrence and survival of the patients with cholangiocarcinoma （CCA） after radical resection， and to establish the nomogram to predict the postoperative survival time.

Methods

The clinical and pathological data of 89 patients who underwent cholangiocarcinoma resection in our hospital were retrospectively collected. The median time of disease-free survival （DFS） and overall survival （OS） of the patients were 10 and 13 months， respectively. Kaplan Meier and Cox regression models were used to analyze the effects of clinical and pathological characteristics on DFS and OS. LASSO regression was performed by R software to evaluate the related influencing factors of recurrence of the patients after surgery. A nomogram was established to predict the OS of patients after operation， and the prediction efficiency was evaluated by the consistency index （C-index）， calibration curve and area under receiver operaing characteristic （ROC） curve （AUC）.

Results

The postoperative univariate analysis showed that diabetes （χ²=5.204， P=0.023）， CA19-9 （χ²=7.694， P=0.006）， CA125 （χ²=6.908， P=0.009）， CA242 （χ²=10.712， P=0.001）， tumor size （χ²=4.310， P=0.038）， lymph node metastasis （χ²=16.883， P<0.001） were the independent risk factors of DFS after operation in the CCA patients. The Kaplan-Meier survival analysis results showed that CEA （χ²=5.188， P=0.023）， CA19-9 （χ²=9.324， P=0.002）， CA125 （χ²=9.568， P=0.002），CA242 （χ²=19.119， P<0.001）， prealbumin （χ²=4.370， P=0.037）， ALT （χ²=4.072， P=0.045），AST （χ²=6.401， P=0.011）， ALP （χ²=4.682， P=0.045）， lymph node metastasis （χ²=11.739，P<0.001），portal carcinoma （χ²=5.940， P=0.015）， vascular invasion （χ²=4.892， P=0.027）， postoperative adjuvant therapy （χ²=4.011， P=0.045） were the risk factors affecting postoperative survival of the CCA patients. The LASSO regression analysis and COX multivariate analysis showed that lymph node metastasis was an independent risk factor of postoperative recurrence of the patients（OR=3.067，95%CI=1.192－8.252，P=0.022）， lymph node metastasis（HR：2.094，95%CI=1.074－4.083，P=0.030） and postoperative adjuvant therapy（HR=0.374，95%CI=0.190－0.736，P=0.004） were the independent factors of survial of the CCA patients. A nomogram was established to predict the OS of CCA patients， Tte C-index was 0.697， and the AUC of the 1-year， 2-year and 5-year survival rates were 0.72 （95%CI： 0.68－0.88），0.65 （95%CI： 0.63－0.81），and 0.84（95%CI： 0.77－0.91），respectively.

Conclusion

The prognosis of CCA patients is poor and the postoperative survival rate is low. Lymph node metastasis is a common independent risk factor for both recurrence and survival. Combined with postoperative adjuvant therapy， a nomogram is constructed， which has a good predictive efficiency in survival in the CCA patients after radical resection.

Key words: Bile duct neoplasms, LASSO regression, Nomogram, Survival analysis, Prognostic factors

CLC Number:

R735.7

Yingjie NIU,Yong ZHA,Sijia LI,Qing WANG,Shicong TANG,Hongyang LI. Analysis on prognosis related factors of patients with cholangiocarcinoma after radical resection and establishment of survival prediction model[J].Journal of Jilin University(Medicine Edition), 2022, 48(4): 979-987.

Figures/Tables 7

Tab.1

Univariate analysis on influencing factors of DFS and OS in CCA patients after radical resection"

Variable	Total number	DFS (months)	χ²	P	OS (months)	χ²	P
Nation			0.199	0.656		0.250	0.617
Han Nationality	73	9.0			12.0
Other	16	14.0			20.0
Age (year)			0.798	0.372		0.914	0.339
<57	40	12.0			14.5
≥57	49	8.0			12.0
Sex			0.608	0.794		0.085	0.771
Male	48	10.5			14.0
Female	41	7.0			10.0
BMI (kg·m^－2)			5.853	0.119		4.352	0.226
<18.5	10	4.0			9.0
18.5—24.0	53	12.0			15.0
24.0—28.0	23	7.0			10.0
≥28.0	3	20.0			25.0
Drinking			0.309	0.587		0.116	0.734
Yes	29	8.0			12.0
No	60	10.0			13.5
Smoking			2.568	0.109		0.512	0.474
Yes	34	11.5			14.5
No	55	9.0			12.0
Hepatitis B			0.004	0.948		0.001	0.980
Yes	19	14.0			14.0
No	70	9.0			12.5
Cirrhosis			0.013	0.910		0.001	0.979
Yes	9	10.0			14.0
No	80	9.5			12.0
Diabetes			5.204	0.023		3.781	0.052
Yes	10	5.0			7.0
No	79	11.0			14.0
Calculus			0.040	0.842		0.046	0.831
Yes	13	15.0			15.0
No	76	8.5			12.0
CEA [ρ_B/(μg·L^－1)]			2.830	0.093		5.188	0.023
≤3.4	45	12.0			18.0
>3.4	44	6.0			9.5
AFP [ρ_B/(μg·L^－1)]			0.000	0.982		0.144	0.2851
≤7	78	9.5			12.0
>7	11	12.0			22.0
CA19-9 [λ_B/(kU·L^－1)]			7.694	0.006		9.324	0.002
≤27	31	15.0			20.0
>27	58	6.0			10.0
CA125 [λ_B/(kU·L^－1)]			6.908	0.009		9.568	0.002
≤35	61	11.0			15.0
>35	28	6.0			9.0
CA15-3 [λ_B/(kU·L^－1)]			2.560	0.110		0.055	0.815
≤25	77	10.0			13.0
>25	12	8.5			13.5
CA72-4 [λ_B/(kU·L^－1)]			0.846	0.358		1.736	0.188
≤6.9	64	10.5			15.0
>6.9	25	4.0			10.0
CA242 [λ_B/(kU·L^－1)]			10.712	0.001		19.119	<0.001
≤20	53	13.0			19.0
>20	36	4.0			7.5
Prealbumin [ρ_B/(mg·L^－1)]			0.010	0.921		4.370	0.037
≤200	35	5.0			8.0
>200	54	12.0			17.0
Total bilirubin [c_B/(μmol·L^－1)]			0.414	0.520		0.323	0.570
≤20	46	8.0			12.0
>20	43	12.0			14.0
ALT [λ_B/(U·L^－1)]			1.086	0.297		4.072	0.045
≤50	56	12.0			19.5
>50	33	8.0			11.0
AST [λ_B/(U·L^－1)]			2.499	0.114		6.401	0.011
≤40	44	12.0			18.0
>40	45	7.0			10.0
ALP [λ_B/(U·L^－1)]			3.386	0.066		4.682	0.045
≤125	34	12.0			20.0
>125	55	5.0			10.0
NLR			0.158	0.691		0.339	0.560
≤2.5	48	8.5			12.0
>2.5	41	12.0			15.0
Child pugh			0.193	0.660		0.321	0.571
A	69	10.0			13.0
B	20	8.5			11.5
Location			0.526	0.769		1.764	0.414
iCCA	44	8.5			12.0
pCCA	23	5.0			12.0
dCCA	22	12.0			16.5
Size (d/cm)			4.310	0.038		2.978	0.084
<5	58	12.0			15.0
≥5	31	5.0			10.0
Lymph node cleaning			1.138	0.286		1.839	0.175
Yes	69	9.0			12.0
No	20	10.5			14.5
Lymph node metastasis			16.883	<0.001		11.739	<0.001
No	42	14.5			19.5
Yes	47	4.0			9.0
Portal carcinoma			1.423	0.233		5.940	0.015
No	64	11.0			16.5
Yes	25	4.0			7.0
Vascular invasion			2.631	0.105		4.892	0.027
No	70	10.5			15.0
Yes	19	4.0			7.0
Postoperative therapy			0.136	0.712		4.011	0.045
Yes	60	12.0			15.0
No	29	3.0			5.0

Tab.1

Fig. 1

Tab.2

Tab.3

Fig. 2

Fig. 3

Fig. 4

References 22

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Variable	HR	95% CI	P
Diabetes	0.711	0.268－1.769	0.464
CA19-9	1.000	1.000－1.000	0.098
CA125	1.004	0.999－1.009	0.098
CA242	1.000	0.999－1.001	0.797
Tumor size	0.770	0.394－1.504	0.444
Lymph node metastasis	2.607	1.444－4.707	0.001

Variable	HR	95% CI	P
CEA	0.764	0.406－1.440	0.406
CA19-9	0.577	0.249－1.338	0.200
CA125	0.669	0.357－1.254	0.210
CA242	0.848	0.380－1.895	0.688
Prealbumin	1.078	0.577－2.012	0.814
ALT	2.203	0.892－5.443	0.087
AST	1.083	0.471－2.490	0.851
ALP	0.482	0.221－1.049	0.066
Lymph node metastasis	2.094	1.074－4.083	0.030
Portal carcinoma	0.873	0.393－1.939	0.740
Vascular invasion	0.891	0.385－2.059	0.786
Postoperative adjuvant therapy	0.374	0.190－0.736	0.004

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Analysis on prognosis related factors of patients with cholangiocarcinoma after radical resection and establishment of survival prediction model

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