Endoscopic retrograde cholangiopancreatography drainage for palliation of malignant hilar biliary obstruction — stent-in-stent or side-by-side? A systematic review and meta-analysis

Table 1 Type of intervention and outcome of study

			Technical success		Clinical success		Rate of early adverse events		Rate of late adverse events		Stent patency		Reintervention		Procedure-related mortality
Ref.	Design	Year	SIS	SBS	SIS	SBS	SIS	SBS	SIS	SBS	SIS	SBS	SIS	SBS	SIS	SBS
Lee et al[33]	RCT	2019	34/34	32/35	32/34	29/35	4/34	4/35	6/34	8/35	Median 253 d (28-420); SD 98; mean 253	Median 262 d (9-455); SD 111.5; mean 262	15/34	12/35	0/34	0/35
Naitoh et al[30]	Cohort	2012	24/24	25/28	24/24	24/28	1/24	3/28	2/24	8/28	Median 104 d (20-600); SD 145; mean 207	Median 155 d (15–881); SD 216.5; mean 155	NA	NA	0/24	0/28
Kim et al[31]	Cohort	2012	18/22	15/19	NA	NA	5/22	6/19	11/22	7/19	NA	NA	NA	NA	NA	NA
Law et al[29]	Cohort	2013	7/7	17/17	NA	NA	NA	NA	0/7	0/17	NA	NA	3/7	9/17	0/7	0/17
Ishigaki et al[32]	Cohort	2020	40/40	23/24	37/40	23/24	9/40	11/24	4/40	3/24	Median 169 d (108-445); SD 84.25; mean 169	Median 205 d (85-NA); SD 24.39; mean 123.75	NA	NA	NA	NA

SIS: Stent-in-stent; SBS: Side-by-side; RCT: Randomized controlled trial; NA: Not available.

Table 2 Risk of bias for ROBINS-I

Ref.	D1	D2	D3	D4	D5	D6	D7	Overall
Naitoh et al[30] 2012	Moderate	Moderate	Low	Low	Low	Moderate	Moderate	Moderate
Kim et al[31] 2012	Serious	Serious	Low	Serious	Serious	Serious	Serious	Serious
Law et al[29] 2013	Moderate	Moderate	Low	Low	Moderate	Moderate	Serious	Moderate
Ishigaki et al[32] 2020	Moderate	Moderate	Low	Low	Low	Moderate	Moderate	Moderate

D: Domains; D1: Bias due to confounding; D2: Bias due to selection of participants; D3: Bias in classification of interventions; D4: Bias due to deviations from intended interventions; D5: Bias due to missing data; D6: Bias in measurement of outcomes; D7: Bias in selection of the reported result.

Table 3 Risk of bias for RoB2

Ref.	D1	D2	D3	D4	D5	Overall
Lee et al[33], 2019	Low	Low	Low	Low	Low	Low

D: Domains; D1: Bias due to randomization process; D2: Bias due to deviations from intended interventions; D3: Bias due to missing outcome data; D4: Bias due to measurement of the outcome; D5: Bias due to selection of the reported result.

Table 4 Description of bias for each outcome (GRADE)

Certainty assessment							Summary of findings
Participants (studies) follow up	Risk of bias	Inconsistency	Indirectness	Imprecision	Publication bias	Overall certainty of evidence	Study event rates (%)		Relative effect (95%CI)	Anticipated absolute effects
							With SBS	With SIS		Risk with SBS	Risk difference with SIS
Early adverse events: Cohorts
157 (3 observational studies)	Serious1	Not serious	Not serious	Not serious	None	Moderate	20/71 (28.2)	15/86 (17.4)	RR 0.54 (0.31 to 0.96)	282 per 1.000	130 fewer per 1.000 (from 194 fewer to 11 fewer)
Early adverse events: RCT
69 (1 RCT)	Not serious	Not serious	Not serious	Serious2	None	Moderate	4/35 (11.4)	4/34 (11.8)	RR 1.03 (0.28 to 3.79)	114 per 1.000	3 more per 1.000 (from 82 fewer to 319 more)
Late adverse events: Cohorts
181 (4 observational studies)	Serious1	Not serious	Not serious	Not serious	None	Moderate	18/88 (20.5)	17/93 (18.3)	RR 0.82 (0.46 to 1.47)	205 per 1.000	37 fewer per 1.000 (from 110 fewer to 96 more)
Late adverse events: RCT
69 (1 RCT)	Not serious	Not serious	Not serious	Serious2	None	Moderate	8/35 (22.9)	6/34 (17.6)	RR 0.77 (0.30 to 1.99)	229 per 1.000	53 fewer per 1.000 (from 160 fewer to 226 more)
Procedural-related mortality: Cohorts
76 (2 observational studies)	Serious1	Not serious	Not serious	Not serious	None	Moderate	0/45 (0.0)	0/31 (0.0)	Not pooled	Not pooled	Not pooled
Procedural-related mortality: RCT
69 (1 RCT)	Not serious	Not serious	Not serious	Not serious	None	High	0/35 (0.0)	0/34 (0.0)	RR 0.00 (-0.05 to 0.05)	0 per 1.000	- per 1.000 (from 0 fewer to 0 fewer)
Technical success: Cohorts
181 (4 observational studies)	Serious1	Not serious	Not serious	Not serious	None	Moderate	80/88 (90.9)	89/93 (95.7)	RR 1.06 (0.97 to 1.16)	909 per 1.000	55 more per 1.000 (from 27 fewer to 145 more)
Technical success: RCT
69 (1 RCT)	Not serious	Not serious	Not serious	Not serious	None	High	32/35 (91.4)	34/34 (100.0)	RR 1.09 (0.97 to 1.22)	914 per 1.000	82 more per 1.000 (from 27 fewer to 201 more)
Clinical success: Cohort
116 (2 observational studies)	Serious1	Serious3	Not serious	Not serious	None	Low	47/52 (90.4)	61/64 (95.3)	RR 1.05 (0.87 to 1.26)	904 per 1.000	45 more per 1.000 (from 118 fewer to 235 more)
Clinical success: RCT
69 (1 RCT)	Not serious	Not serious	Not serious	Not serious	None	High	29/35 (82.9)	32/34 (94.1)	RR 1.14 (0.96 to 1.35)	829 per 1.000	116 more per 1.000 (from 33 fewer to 290 more)
Reintervention: Cohort
24 (1 observational study)	Serious1	Not serious	Not serious	Serious2	None	Low	9/17 (52.9)	3/7 (42.9)	RR 0.81 (0.31 to 2.13)	529 per 1.000	101 fewer per 1.000 (from 365 fewer to 598 more)
Reintervention: RCT
69 (1 RCT)	Not serious	Not serious	Not serious	Not serious	None	High	12/35 (34.3)	15/34 (44.1)	RR 1.29 (0.71 to 2.33)	343 per 1.000	99 more per 1.000 (from 99 fewer to 456 more)
Stent patency: Cohort
116 (2 observational studies)	Serious1	Not serious	Not serious	Not serious	None	Moderate	52	64	-	The mean stent patency: Cohort was 0	MD 45.75 higher (18.92 higher to 72.58 higher)
Stent patency: RCT
69 (1 RCT)	Not serious	Not serious	Not serious	Not serious	None	High	35	34	-	The mean stent patency: RCT was 0	MD 9 lower (58.49 lower to 40.49 higher)

¹There are risk of bias in selection of the reported result, according to ROBINS-I tool.

²Wide confidence interval range.

³High heterogeneity, calculated using the Higgins method (I²).

CI: Confidence interval; RR: Risk ratio; MD: Mean difference; RCT: Randomized controlled trial.