Differentiation of intrahepatic cholangiocarcinoma from hepatocellular carcinoma in high-risk patients: A predictive model using contrast-enhanced ultrasound

doi:10.3748/wjg.v24.i33.3786

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World Journal of Gastroenterology

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World J Gastroenterol. Sep 7, 2018; 24(33): 3786-3798
Published online Sep 7, 2018. doi: 10.3748/wjg.v24.i33.3786

Table 1 Demography of patients with intrahepatic cholangiocarcinoma or hepatocellular carcinoma n (%)

Characteristic	Training set (n = 117)		Validation set (n = 59)		P value
Characteristic	ICC	HCC	ICC	HCC	P value
Number of patients	56 (47.9)	61 (52.1)	32 (27.4)	27 (23.1)	0.425
Gender					0.148
Male	35 (29.9)	56 (47.9)	24 (20.5)	21 (17.9)
Female	21 (17.9)	5 (4.3)	8 (6.8)	6 (5.1)
Age (yr)¹	55 ± 11 (32-84)	55 ± 11 (32-84)	53 ± 10 (18-76)	57 ± 11 (33-82)	0.646
Hepatitis status					0.627
Hepatitis B	53 (45.3)	59 (50.4)	31 (26.5)	27 (23.1)
Hepatitis B + C	3 (2.6)	2 (1.7)	1 (0.9)	0 (0)
AFP > 20 (μg/L)	11 (9.4)	29 (24.8)	3 (2.6)	11 (9.4)	0.655
CA 19-9 > 35 (U/mL)	22 (18.8)	6 (5.1)	15 (12.8)	3 (2.6)	0.691
Nodule size					0.782
≤ 3.0 cm	5 (4.3)	9 (7.7)	2 (1.7)	3 (2.6)
3.1-5.0 cm	9 (7.7)	17 (14.5)	8 (6.8)	6 (5.1)
> 5.0 cm	42 (35.9)	35 (29.9)	22 (18.8)	18 (15.4)
Number of nodules					0.156
One	39 (33.3)	42 (35.9)	25 (21.4)	24 (20.5)
Multiple	17 (14.5)	19 (16.2)	7 (6.0)	3 (2.6)

¹Data are means ± SD, with ranges in parentheses. Unless otherwise indicated, data are number of nodules, with percentages in parentheses. ICC: Intrahepatic cholangiocarcinoma; HCC: Hepatocellular carcinoma.

Table 2 Comparison and univariate analysis of contrast-enhanced ultrasound features between intrahepatic cholangiocarcinoma and hepatocellular carcinoma n (%)

CEUS features	ICC¹ (n = 62)	HCC¹ (n = 55)	P value	OR	(95%CI)
Irregular shape	31 (50.0)	9 (16.4)	0.000	5.037	(2.002, 13.786)
Hyper-enhanced in arterial phase	55 (88.7)	54 (98.2)	0.065	0.147	(0.003, 1.210)
Hypo/iso-enhanced in arterial phase	7 (11.3)	1 (1.8)	0.065	6.783	(0.827, 314.886)
Hypo-enhanced in portal phase	61 (98.4)	40 (72.7)	0.000	22.391	(3.206, 973.549)
Hypo-enhanced in late phase	61 (98.4)	51 (92.7)	0.186	4.728	(0.449, 239.097)
Rim-enhancement	40 (64.5)	1 (1.8)	0.000	94.271	(14.202, 3946.676)
Early washout (< 60 s)	57 (91.9)	17 (30.9)	0.000	24.563	(8.022, 92.533)
Duration of enhancement (< 30 s)	49 (79.0)	11 (20)	0.000	14.614	(5.653, 41.160)
Tumor supply artery	12 (19.4)	29 (52.7)	0.000	4.581	(1.904, 11.618)
Peripheral circular artery or tumor capsule	2 (3.2)	14 (25.5)	0.000	10.060	(2.137, 95.937)
Intra-tumoral vein	36 (58.1)	2 (3.6)	0.000	35.556	(8.118, 327.503)
Obscure boundary of tumor	43 (69.4)	12 (21.8)	0.000	7.942	(3.268, 20.550)
Obscure boundary of intra-tumoral non-enhanced area	40 (64.5)	1 (1.8)	0.000	94.271	(14.202, 3946.676)
Marked washout	38 (61.3)	1 (1.8)	0.000	82.367	(12.448, 3454.264)

¹Data are number of cases, with percentages in parentheses. CEUS: Contrast-enhanced ultrasound; ICC: Intrahepatic cholangiocarcinoma; HCC: Hepatocellular carcinoma; OR: Odds ratio.

Table 3 Comparison of the diagnostic performance of the contrast-enhanced ultrasound score vs contrast-enhanced ultrasound liver imaging reporting and data system in distinguishing intrahepatic cholangiocarcinoma from hepatocellular carcinoma

	Sensitivity	Specificity	PPV	NPV	Accuracy	AUC	(95%CI)	P value
Training set (n = 117)
CEUS LI-RADS	0.936	0.691	0.773	0.905	0.821	0.813	(0.744, 0.882)	0.000
CEUS score	0.871	0.946	0.947	0.867	0.906	0.958	(0.924, 0.993)	0.000
Validation set (n = 59)
CEUS LI-RADS	1.000	0.485	0.605	1.000	0.712	0.742	(0.656, 0.829)	0.000
CEUS score	0.885	0.909	0.885	0.909	0.898	0.953	(0.907, 0.999)	0.000
≤ 5.0 cm subgroup (n = 59)
CEUS LI-RADS	0.917	0.600	0.611	0.913	0.729	0.758	(0.658, 0.858)	0.000
CEUS score	0.750	0.886	0.818	0.838	0.831	0.902	(0.824, 0.980)	0.000
≤ 3.0 cm subgroup (n = 19)
CEUS LI-RADS	0.857	0.750	0.667	0.900	0.790	0.804	(0.614, 0.993)	0.512
CEUS score	0.571	0.917	0.800	0.786	0.790	0.833	(0.636, 1.000)	0.512

Numbers are raw data. P values were CEUS Score vs CEUS LI-RADS. CEUS: Contrast-enhanced ultrasound; LI-RADS: Liver imaging reporting and data system; ICC: Intrahepatic cholangiocarcinoma; HCC: Hepatocellular carcinoma; PPV: Positive predictive value; NPV: Negative predictive value; AUC: Area under the ROC curve.

Table 4 Univariate and multivariate logistic regression of independent variables in the prediction of intrahepatic cholangiocarcinoma

Factors	Univariate analysis		Multivariate analysis
Factors	OR (95%CI)	P value	OR (95%CI)	P value
Gender (female)	0.149 (0.046, 0.403)	< 0.001	0.190 (0.034,0.908)	0.044
Age (yr)
> 40	0.786 (0.220, 2.618)	0.696	NA	NA
> 50	1.630 (0.778, 3.450)	0.197	NA	NA
AFP (mg/L) > 20	0.331 (0.148, 0.717)	0.006	0.508 (0.107, 2.212)	0.370
CA199 (U/mL) > 35	10.577 (4.152, 31.070)	< 0.001	5.352 (1.108, 30.336)	0.043
CEUS score	12.188 (5.475, 37.787)	< 0.001	14.078 (5.608, 52.831)	< 0.001

Numbers in parentheses are raw data, with 95%CI in parentheses. ICC: Intrahepatic cholangiocarcinoma; OR: Odds ratio; NA: Not available; AFP: Alpha-fetoprotein; CEUS: Contrast-enhanced ultrasound.

Table 5 Comparison of the AUC, NRI and IDI of the contrast-enhanced ultrasound score nomogram vs contrast-enhanced ultrasound liver imaging reporting and data system nomogram in distinguishing intrahepatic cholangiocarcinoma from hepatocellular carcinoma

	AUC	(95%CI)	P value	NRI	(95%CI)	P value	IDI	(95%CI)	P value
Training set (n = 117)
CEUS LI-RADS nomogram	0.891	(0.834, 0.948)	< 0.001	0.446	(0.263, 0.629)	< 0.001	0.210	(0.140, 0.280)	< 0.001
CEUS score nomogram	0.971	(0.948, 0.995)	< 0.001	0.446	(0.263, 0.629)	< 0.001	0.210	(0.140, 0.280)	< 0.001
Validation set (n = 59)
CEUS LI-RADS nomogram	0.916	(0.854, 0.978)	0.036	0.077	(-0.141, 0.295)	0.488	0.152	(0.044, 0.260)	0.006
CEUS score nomogram	0.973	(0.941, 1.000)	0.036	0.077	(-0.141, 0.295)	0.488	0.152	(0.044, 0.260)	0.006
≤ 5.0 cm subgroup (n = 59)
CEUS LI-RADS nomogram	0.835	(0.744, 0.926)	0.008	0.382	(0.069, 0.695)	0.017	0.177	(0.065, 0.289)	0.002
CEUS score nomogram	0.929	(0.870, 0.988)	0.008	0.382	(0.069, 0.695)	0.017	0.177	(0.065, 0.289)	0.002
≤ 3.0 cm subgroup (n = 19)
CEUS LI-RADS nomogram	0.881	(0.732, 1.000)	0.601	-0.202	(-0.572, 0.167)	0.283	-0.117	(-0.284, 0.050)	0.171
CEUS score nomogram	0.905	(0.772, 1.000)	0.601	-0.202	(-0.572, 0.167)	0.283	-0.117	(-0.284, 0.050)	0.171

Numbers are raw data. P values were CEUS Score nomogram vs CEUS LI-RADS nomogram. AUC: Area under the ROC curve; NRI: Net reclassification improvement; IDI: Integrated discriminatory improvement; CEUS: Contrast-enhanced ultrasound; LI-RADS: Liver imaging reporting and data system; ICC: Intrahepatic cholangiocarcinoma; HCC: Hepatocellular carcinoma.

Citation: Chen LD, Ruan SM, Liang JY, Yang Z, Shen SL, Huang Y, Li W, Wang Z, Xie XY, Lu MD, Kuang M, Wang W. Differentiation of intrahepatic cholangiocarcinoma from hepatocellular carcinoma in high-risk patients: A predictive model using contrast-enhanced ultrasound. World J Gastroenterol 2018; 24(33): 3786-3798
URL: https://www.wjgnet.com/1007-9327/full/v24/i33/3786.htm
DOI: https://dx.doi.org/10.3748/wjg.v24.i33.3786