Diagnostic value for extrahepatic metastases of hepatocellular carcinoma in positron emission tomography/computed tomography scan

Table 1 Patients baseline characteristics

	n = 138	%
Age	59.6 ± 11.1 (range: 33-84)
Sex
M/F	114/24	82.6/17.4
Etiology of liver disease
HBV/HCV/alcohol/unknown	89/15/10/24	64.5/10.9/7.2/17.4
AFP (ng/mL)	9512.9 ± 23 026.4
PIVKAII (mAU/mL)	854.2 ± 871.7
Tumor morphology
Nodular/infiltrating	78/60	56.5/43.6
Tumor size (mm)	69.8 ± 45.2
Tumor number
1/≥ 2	52/86	37.7/62.3
PVTT
Yes	54	39.1
Child-Pugh classification
A/B/C	77/56/5	55.8/40.6/3.6
Tumor stage1
I/II/III/IVa/IVb	7/34/26/22/49	5.1/24.6/18.8/15.9/35.5
SUV
Iso-/hypometabolism	42/3	30.4/2.2
Hypermetabolism	93	67.4
Maximum	5.32 ± 2.38
Average	4.03 ± 1.26
TNR (SUV ratio)	1.60 ± 0.49
Extrahepatic metastases	50	36.2
Lung	23	46.0
Lymph nodes	22	44.0
Bone	11	22.0
Others2	5	10.0

¹Tumor stage based on the Modified Union for International Cancer Control Tumor Node Metastasis staging system;

²Others: Adrenal gland, peritoneal carcinomatosis, Morrison’s pouch. HBV: Hepatitis B virus; HCV: Hepatitis C virus; AFP: α-fetoprotein; PIVKAII: Protein induced by vitamin K antagonist II; PVTT: Portal vein tumor thrombosis; SUV: Standardized uptake value; TNR: Tumor-to-nontumor ratio.

Table 2 Correlation of histologic grade with clinical factors and tumor characteristics n (%)

	Low-grade (n = 34)	High-grade (n = 12)	P value1
Age	61.7 ± 8.4	56.5 ± 6.7	0.055
Sex			0.260
M/F	32 (94.1)/2	10 (83.3)/2
Etiology of liver disease			0.431
HBV/HCV/alcohol/unknown	21/2/2/9	9/0/1/2
AFP (ng/mL)	2892.0 ± 9255.6	2960.5 ± 9554.0	0.930
<200/≥ 200	26 (76.5)/8	10 (83.3)/2
PIVKAII (mAU/mL) (n = 20/n = 7)	758.4 ± 823.1	798.6 ± 879.6	1.000
< 40/≥ 40	3 (15)/17	1 (16.7)/6
Tumor morphology			0.441
Nodular/infiltrating	24 (70.6)/10	8 (66.7)/4
Tumor size			0.643
< 5/≥ 5	16 (47.1)/18	7 (58.3)/5
Tumor number			0.297
1/≥ 2	20 (58.8)/14	9 (75)/3
PVTT			0.259
Yes	8 (23.5)	1 (8.3)
Child-Pugh classification			0.563
A/B/C	30 (88.2)/4/0	11(91.7)/1/0
T stage			0.537
1/2/3/4	3/15/9/7	1/7/2/2
SUV
Isometabolism	14 (41.2)	2 (16.7)	0.061
Hypometabolism	2	0
Hypermetabolism (n = 18/n = 10)
Maximum	3.75 ± 0.74	5.75 ± 2.15	0.027
Average	3.30 ± 0.42	4.15 ± 1.17	0.226
TNR (SUV ratio)	1.33 ± 0.22	1.64 ± 0.52	0.286

HBV: Hepatitis B virus; HCV: Hepatitis C virus; AFP: α-fetoprotein; PIVKAII: Protein induced by vitamin K antagonist II; PVTT: Portal vein tumor thrombosis; SUV: Standardized uptake value; TNR: Tumor-to-nontumor ratio.

¹Statistical significance test was done by U test.

Table 3 Diagnostic value of ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography scan and conventional imaging modalities for detection of extrahepatic metastases

	Lung metastases (n = 23)		Lymph node metastases (n = 22)		Bone metastases (n = 11)
	TP	TN	TP	TN	TP	TN
PET (+)	14	1	20	4	11	0
Conventional (+)	23	2	22	4	7	4
	PET	Conventional	PET	Conventional	PET	Conventional
Sensitivity, %	60.9	100	90.9	100	100	63.6
Specificity, %	99.1	98.2	96.5	96.5	100	96.8
Accuracy, %	92.6	98.5	95.6	97.1	100	94.1
PPV, %	93.3	92	83.3	84.6	100	63.6
NPV, %	92.5	100	98.2	100	100	96.8
Comparison of ROC curves	P = 0.000		P = 0.269		P = 0.010
	(CI: 0.0888-0.294)				(CI: 0.0481-0.348)

TP: True positive; TN: True negative; PPV: Positive predictive value; NPV: Negative predictive value; ROC: Receiver operating characteristic; PET: Positron emission tomography.

Table 4 Clinical factors and tumor characteristics of extrahepatic metastases in hepatocellular carcinoma

	Metastasis (n = 50)	No metastasis (n = 88)	P value
			Uni	Multi
Age	58.7 ± 11.1	60.1 ± 11.1	0.480
Sex			0.285
M/F	39/11	75/13
Etiology of liver disease			0.215
HBV/HCV/alcohol/unknown	31/3/4/12	58/12/6/12
AFP (ng/mL)	15 568.8 ± 28 119.6	6072.1 ± 18 882.3	0.019	0.254
< 200/≥ 200 (%)	21/29 (58.0)	59/29 (33.0)
PIVKAII (mAU/mL)	1320.5 ± 784.0	630 ± 827.9	0.001
< 40/≥ 40 (n = 25/n = 52) (%)	2/23 (92.0)	18/34 (65.4)
Tumor morphology			0.000	0.126
Nodular/infiltrating (%)	17/33 (66.0)	61/27 (30.7)
Tumor size	88.9 ± 40.2	58.9 ± 44.5	0.000	0.0421
< 5/≥ 5 (%)	7/43 (86.0)	48/40 (45.5)
Tumor number			0.000	0.382
1/≥ 2 (%)	7/43 (86.0)	45/43 (48.9)
PVTT			0.000	0.330
Yes (%)	30 (60.0)	24 (27.2)
Child-Pugh classification			0.474
A/B/C	35/11/4	68/19/1
T stage			0.000	0.197
1/2/3/4 (%)	1/4/12/33 (66.0)	7/34/26/21 (23.9)
SUV
Isometabolism (%)	3 (6.0)	39 (44.3)	0.000	0.035
Hypometabolism	0	3
Hypermetabolism (n = 47)
Maximum	5.89 ± 2.55	4.74 ± 2.05	0.019	0.517
Average	4.38 ± 1.35	3.68 ± 1.05	0.006	0.0282
TNR (SUV ratio)	1.70 ± 0.51	1.50 ± 0.45	0.048	0.352
Pathology			0.042
Low-/high-grade (n = 12/n = 34) (%)	7 (58.3)/5	27 (79.4)/7

¹1.06-31.8;

²1.3-127.9. HBV: Hepatitis B virus; HCV: Hepatitis C virus; AFP: α-fetoprotein; PIVKAII: Protein induced by vitamin K antagonist II; PVTT: Portal vein tumor thrombosis; SUV: Standardized uptake value; TNR: Tumor-to-nontumor ratio.

Table 5 Clinical factors that affected survival by multivariate analysis

	Odds ratio	CI	P value
Child class B	4.784	2.575-8.891	0.000
Child class C	10.787	3.579-32.511	0.000
AFP (> 200 ng/mL)	1.825	0.998-3.338	0.051
Tumor size (> 5 cm)	1.004	1.000-1.009	0.060
Metastases	2.069	1.152-3.715	0.015