Preoperative transarterial chemoembolization for resectable hepatocellular carcinoma in Asia area: a meta-analysis of random controlled trials

Figures & data

Figure 1. The flowchart of the study screening and the detailed selection process.

Table 1. Clinical background of studies included in the meta-analysis.

Author	group	Tumor diameter (cm)	Gender (M/F)	Age (years)	Child-Pugh (A + B/C)	Tumor No. (Single/Multiple)	TNM staging (I + II/III + IV)	Cirrhosis	Matching	Complete necrosis rate
Kaibori [19]	Pre-TACE	4.30 ± 2.13	35/7	68.1 ± 5.7	37 + 5/0	32/10	31/11	14/42	(1)(2)(3)(4)(5)(6)	9/42(21.42%)
	Control	4.86 ± 4.12	32/11	66.1 ± 10.6	39 + 4/0	32/11	31/12	11/43
Zhou [20]	Pre-TACE	9.0 ± 3.2	48/4	45.3 ± 9.8	44 + 8/0	NR	25/22	49/52	(1)(2)(3)(4)(5)(6)(7)	7/47(14.89%)
	Control	9.5 ± 3.9	49/7	46.8 ± 9.6	54 + 2/0	NR	31/25	50/56
Cui [21]	Pre-TACE	8.33 ± 4.49	32/12	48.3 ± 8.77	44/0	NR	NR	NR	(1)(2)(3)(4)(5)(6)(7)	8/44(18.18%)
	Control	8.16 ± 5.28	30/14	47.3 ± 8.91	44/0	NR	NR	NR
Yamasaki [22]	Pre-TACE	3.1 ± 0.8	50/0	54.9 ± 6.4	NR	42/4	NR	NR	(4)(5)(6)	16/50(32%)
	Control	3.3 ± 0.9	47/0	57.1 ± 4.9	NR	38/7	NR	NR
Wu [23]	Pre-TACE	14.3 ± 4.2	23/1	51.8 ± 12.4	22 + 2/0	NR/4	4/20	14/24	(1)(2)(3)(4)(5)(6)(7)	0/24(0%)

TACE: transarterial chemoembolization; NR: Not Reported;TNM: Tumor Node Metastasis (1) operation time; (2) blood loss; (3) postoperative morbidity; (4) perioperative mortality; (5) disease free survival; (6) overall survival; (7) combined resection of perihepatic organs.

Numbers are mean value ± standard deviation. Complete necrosis rate are measured by histopathology examination.

Table 2. Interventions of included trials.

Author	Drugs and dosage of TACE	Mean numberof courses	Mean interval (d)	Results	Prognosis
Kaibori [19]	Epirubicin (28.1 ± 5.5 mg) + Lipiodol (2.9 ± 1.4 ml) + gelatin sponge particles in tumor area; epirubicin (22.2 ± 6.2 mg) + Lipiodol (1.9 ± 0.8 ml) into non-cancerous liver	1.9	23.0	No effect	TACE do not reduce the incidence of postoperative recurrence or prolong survival in patients with resectable HCC
Zhou [20]	Emulsion of 5-fluorouracil (1 g) + mitomycin C (20 mg) + cisplatin (5 mg) + lipiodol 10–30 ml (1–2 ml/cm diameter of the tumor)	1.5	58.8	Suggested unfavourable	TACE did not improve surgical outcome and result in drop-out from definitive surgery.
Cui [21]	Mitomycin(20–30 mg) + carboplatin(80–100mg) + fluorouracil(700–1000 mg) + lipiodol 8–30 ml (1ml/diameter cm) + gelatin sponge	NR	NR	Suggested unfavourable	TACE was associated with a higher prevalence of intra-operative adhesion in patients underwent hepatectomy
Yamasaki [22]	Doxorubicin(20 mg) + Urografin (2.5 ml) + lipiodol (5 ml) + gelatin sponge (1–3 ml)	1	NR	No effect	TACE before hepatectomy is no effective against such HCC accessory lesions and does not influence overall survival and disease-free survival
Wu [23]	Doxorubicin(20–30 mg) + cisplatin(2.5–50 mg) + lipiodol(20–30 ml) + gelatin sponge	2.5	112.7	Suggested unfavourable	TACE does not provide complete necrosis in large tumors and results in delayed surgery and difficulty in the treatment of recurrent lesions, without any benefit.

Table 3. Bias assessment of studies included in the meta-analysis.

	Cochrane risk of bias table on the Prognosis for Patients with resectable HCC
	Kaibori [19]	Zhou [20]	Yamasaki [22]	Wu [23]	Cui [21]
Random sequence generation	Unclear risk (the method of randomizationgeneration was not described)	Unclear risk (the method of randomizationgeneration was not described)	Unclear risk (the method of randomizationgeneration was not described)	Unclear risk (the method of randomizationgeneration was not described)	Unclear risk (the method of randomizationgeneration was not described)
Allocation concealment	Unclear risk (whether using sealed, opaque or successive coded envelope was not mentioned)	Low risk (Using sealed, opaque and successive coded envelope)	Unclear risk (whether using sealed, opaque or successive coded envelope was not mentioned)	Unclear risk (information is not complete)	Unclear risk (information is not complete)
Blinding of outcomes	Unclear risk (information was not complete)	Unclear risk (information was not complete)	Unclear risk (information was not complete)	Unclear risk (information was not complete)	Unclear risk (information was not complete)
Incomplete outcomedata	Low risk (the results were relatively complete, missing data could be ignored)	Low risk (the results were relatively complete, missing data could be ignored)	High risk (incidence of loss to follow-up was up to 10% in pre-TACE group and 20% incontrol group)	Unclear risk (no direct data about overallsurvival and disease free survival)	High risk (the data of overall survival rate was incomplete)
Selective reporting	Low risk (predetermined indicators were definite)	Low risk (predetermined indicators were definite)	High risk (incomplete data and uncertainprimary outcome indicators)	High risk (incomplete data and uncertainprimary outcome indicators)	High risk (incomplete data and uncertainprimary outcome indicators)
Other bias	High risk (significantly different in the level of AFP and tumor stage among groups)	Unclear risk (information was not complete)	Unclear risk (information was not complete)	Unclear risk (information was not complete)	Unclear risk (information was not complete)

Figure 2. (A) Forest plot of the subgroup analysis on the DFS. (B) Forest plot of the subgroup analysis on the OS.

Figure 3. (A) Forest plot of the subgroup analysis on the perioperative mortality. (B) Forest plot of the subgroup analysis on the postoperative morbidity

Figure 4. (A) Forest plot of the subgroup analysis on the blood loss. (B) Forest plot of the subgroup analysis on the operation time

Figure 5. Forest plot of the subgroup analysis on the combined resection of perihepatic organs.

Figure 6. The funnel plot for overall disease-free survival of the included studies.

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