Endoscopic biliary treatment of unresectable cholangiocarcinoma: A meta-analysis of survival outcomes and systematic review

Table 1 Summary of included studies

Ref.	Country	Study type	Total patients	Mean age	Female gender (%)	Chemotherapy
Sampath et al[23], 2016	United States	Case-Control	25	69.7	10 (40.0)	19 (76)
Hu et al[21], 2016	China	RCT	63	71.4	32 (50.8)	-
Wu et al[26], 2017	China	Case-Control	71	57.9	28 (39.2)	59 (83)
Cui et al[25], 2017	China	Case-Control	39	64.7	17 (43.5)	2 (5)
Yang et al[22], 2018	China	RCT	65	63.2	32 (49.2)	-
Bokemeyer et al[24], 2019	Germany	Case-Control	44	67	-	13 (30)

RCT: Randomized controlled trial.

Table 2 Procedural and survival outcomes of individual studies

Ref.	Total patients		Technical success		Major adverse events		Mean survival (mean ± SD)		P valuea
	Stent only	RFA-stent	Stent only	RFA-stent	Stent only	RFA-stent	Stent only	RFA-stent
Endoscopic
Sampath et al[23], 2016	15	10	-	100	8	9	4.7 ± 5.5	12 ± 5.9	0.001
Hu et al[21], 2016	31	32	-	-	22	26	5.7 ± 0.5	10.4 ± 1.2	0.001
Yang et al[22], 2018	33	32	100	100	3	2	8.3 ± 0.5	13.2 ± 0.6	< 0.001
Bokemeyer et al[24], 2019	22	20	100	100	10	4	7.4 ± 0.9	11.4 ± 1.9	0.046
Percutaneous
Wu et al[26], 2017	36	35	-	100	5	0	6.5 ± 2.6	8.4 ± 2.3	0.80
Cui et al[25], 2017	14	25	-	-	-	-	4.5 ± 2.1	6.7 ± 5.3	0.30

^aP value as it relates to mean survival in each respective study. SD: Standard deviation; RFA: Radiofrequency ablation.

Table 3 Pooled stent patency analysis among included endoscopic radiofrequency ablation studies

Ref.	Stent only patients (%)	Mean stent patency	ERFA-stent patients (%)	Mean stent patency	P value
Hu et al[21], 2016	31 (48.5)	3.9	32 (50)	5	0.7
Yang et al[22], 2018	33 (51.5)	3.4	32 (50)	6.8	0.02
Cumulative	64	3.6	64	5.9	< 0.001

ERFA: Endoscopic radiofrequency ablation.

Table 4 Pooled adverse event data among included endoscopic radiofrequency ablation studies

Adverse event	ERFA-stent n (%)	Stent alonen (%)	P value
Biliary stent occlusion	34 (81.0)	31 (67.3)	0.148
Cholangitis	27 (25.5)	15 (19.0)	0.298
Cholecystitis	8 (12.5)	0 (0)	0.010
Pancreatitis	4 (4.2)	3 (4.7)	0.875
Hemobilia/Bleeding	1 (1.5)	1 (1.5)	1.000

ERFA: Endoscopic radiofrequency ablation.

Table 5 Demographics, procedural, and survival outcomes of endoscopic radiofrequency ablation vs photodynamic therapy

	Demographic data
	Strand et al[13], 2014				Schmidt et al[15], 2016				Gao et al[14], 2018
Number of patients	RFA	16		P = 0.1	RFA	14		NA	RFA
	PDT	32			PDT	20			PDT
Gender (male)	RFA	10		P = 1.0	RFA	8		P = 0.1	RFA
	PDT	19			PDT	6			PDT
Age (mean, yr)	RFA	64.3 ± 11.9		P = 0.1	RFA	73 ± 9		P = 0.2	RFA
	PDT	69.5 ± 13.6			PDT	70 ± 12			PDT
Number of treatments	RFA	28 (mean: 1.2)		P = 0.02	RFA	31		NA	RFA
	PDT	60 (mean: 2.1)			PDT	36			PDT
Median survival (month)	RFA	9.6		P = 0.8	RFA	NA		NA	RFA
	PDT	7.5			PDT	NA			PDT
Lead time to initial treatment (days)	RFA	NS		P = 0.6	RFA	300 ± 270		NA	RFA
	PDT	NS			PDT	120 ± 90			PDT
Total bilirubin concentration (µmol/dL)	RFA	NA		NA	RFA	3.3 ± 3.9		P = 0.7	RFA
	PDT	NA			PDT	4.1 ± 6.9			PDT
Tumor location	RFA	Intrahepatic	1	P = 0.1	RFA	Intrahepatic	1	P = 0.5	RFA
		Hilar	13			Hilar	11
		Distal/Extrahepatic	2			Distal/Extrahepatic	1
	PDT	Intrahepatic	0		PDT	Intrahepatic	3		PDT
		Hilar	32			Hilar	15
		Distal/Extrahepatic	0			Distal/Extrahepatic	1
N1 staging	RFA	7		P = 0.8	RFA	3		P = 0.4	RFA
	PDT	12			PDT	2			PDT
M1 staging	RFA	6		P = 0.2	RFA	2		P = 0.8	RFA
	PDT	6			PDT	6			PDT
Stents placed	Total	RFA	115	NA	Total	RFA	29	NA	Total
		PDT	307			PDT	44
	Plastic	RFA	69	NA	Plastic	RFA	26	NA	Plastic
		PDT	264			PDT	38
	Total metallic	RFA	46	NA	Total metallic	RFA	3	NA	Total metallic
		PDT	43			PDT	6
	Fully covered	RFA	17	NA	Fully covered	RFA	NA	NA	Fully covered
		PDT	14			PDT	NA
	Uncovered	RFA	29	NA	Uncovered	RFA	NA	NA	Uncovered
		PDT	29			PDT	NA
Number of ERCPs	RFA	91		NA	RFA	NA		NA	RFA
	PDT	170			PDT	NA			PDT
Percutaneous transhepatic biliary drainage (PTBD)	RFA	2		P = 0.2	RFA	2		P = 0.3	RFA
	PDT	10			PDT	6			PDT

RFA: Radiofrequency ablation; PDT: Photodynamic therapy; NA: Not available; NS: Not significant; P: P vaule as it relates to each comparator category.

Table 6 Adverse events of endoscopic radiofrequency ablation vs photodynamic therapy

Adverse events
	RFA	PDT	P value
Stent related complications	17	17	0.7
Stent occlusion	14	5	0.008
Stent migration	3	12	0.04
Cholangitis	46	31	0.001
Hepatic abscess	4	3	0.5
Bleeding	1	1	0.9
Moderate/Severe abdominal pain	3	17	0.003
Post-ERCP pancreatitis	3	2	0.5
Phototoxicity	0	2	NA

ERCP: Endoscopic retrograde cholangiopancreatography; NA: Not applicable; RFA: Radiofrequency ablation; PDT: Photodynamic therapy; P: P vaule as it relates to comparisons of each adverse event.