Video capsule endoscopy vs double-balloon enteroscopy in the diagnosis of small bowel bleeding: A systematic review and meta-analysis

Table 1 QUADAS-2. Risk of bias in individual studies

Study	Hadithi et al, 2006[4]	Hermans et al, 2017[11]	Holleran et al, 2014[37]	Kaffes et al, 2007[34]	Kalra et al, 2015[16]	Kamalapor et al, 2008[30]	Kameda et al, 2008[27]	Li et al, 2010[35]	Lin et al, 2007[40]	Maeda et al, 2015[32]	Marmo et al, 2009[23]	TianMin, et al, 2013[39]	Nakamura et al, 2006[29]	Rahmi et al, 2013[33]	Chu et al, 2016[17]	Zhang, et al, 2015[15]
Was a consecutive or random sample of patients enrolled?	YES	UNCLEAR	UNCLEAR	YES	UNCLEAR	UNCLEAR	YES	YES	YES	YES	YES	YES	YES	YES	YES	UNCLEAR
Was a case-control design avoided?	YES	YES	NO	YES	YES	NO	YES	YES	YES	YES	YES	YES	YES	YES	YES	YES
Did the study avoid inappropriate exclusions?	YES	YES	YES	YES	UNCLEAR	NO	YES	YES	YES	YES	YES	YES	YES	YES	YES	NO
Could the selection of patients have introduced bias?	LOW	MODERATE	HIGHT	LOW	HIGH	HIGH	LOW	LOW	LOW	LOW	LOW	LOW	LOW	LOW	LOW	HIGH
Are there concerns that the included patients do not match the review question?	LOW	LOW	LOW	LOW	LOW	LOW	LOW	LOW	LOW	LOW	LOW	LOW	LOW	LOW	LOW	HIGH
Were the index test results interpreted without knowledge of the results of the reference standard?	YES	NO	YES	NO	YES	NO	YES	UNCLEAR	UNCLEAR	UNCLEAR	YES	NO	YES	NO	NO	UNCLEAR
If a threshold was used, was it prespecified? Could the conduct or interpretation of the index test have introduced bias?	YES LOW	YES MODERATE	YES LOW	YES MODERATE	NO MODERATE	YES MODERATE	YES LOW	YES MODERATE	NO MODERATE	YES MODERATE	YES LOW	NO HIGH	YES LOW	YES MODERATE	YES MODERATE	YES MODERATE
Are there concerns that the index test, its conduct, or interpretation differ from the review question?	LOW	LOW	LOW	LOW	LOW	LOW	LOW	LOW	LOW	LOW	LOW	LOW	LOW	LOW	LOW	HIGH
Is the reference standard likely to correctly classify the target condition?	YES	YES	YES	YES	YES	YES	YES	YES	YES	YES	YES	YES	YES	YES	NO	UNCLEAR
Were the reference standard results interpreted without knowledge of the results of the index test?	YES	NO	YES	NO	YES	YES	YES	YES	YES	YES	YES	YES	YES	YES	YES	UNCLEAR
Could the reference standard, its conduct, or its interpretation have introduced bias?	LOW	MODERATE	LOW	MODERATE	LOW	LOW	LOW	LOW	LOW	LOW	LOW	LOW	LOW	LOW	HIGH	HIGH
Are there concerns that the target condition as defined by the reference standard does not match the review question?	LOW	LOW	LOW	LOW	LOW	LOW	LOW	LOW	LOW	LOW	LOW	LOW	LOW	LOW	HIGH	HIGH
Was there an appropriate interval between index test(s) and reference standard?	YES	NO	NO	NO	NO	NO	YES	YES	YES	YES	YES	YES	YES	NO	YES	UNCLEAR
Did all patients receive a reference standard?	YES	YES	YES	YES	YES	YES	YES	YES	YES	YES	YES	YES	YES	YES	YES	YES
Did all patients receive the same reference standard?	NO	YES	YES	YES	YES	YES	YES	YES	YES	YES	YES	YES	YES	YES	YES	YES
Were all patients included in the analysis?	YES	YES	YES	YES	YES	YES	YES	YES	YES	YES	YES	YES	YES	YES	YES	YES
Could the patient flow have introduced bias?	MODERATE	LOW	LOW	LOW	LOW	MODERATE	LOW	LOW	LOW	LOW	LOW	LOW	LOW	MODERATE	LOW	LOW

Table 2 Studies characteristics

	Median age; range	Patient total	Study design	VCE Model	DBE Model	Preparation	Interval CE × DBE	No. of patients with diagnoses of SBB by CE/total CE performed	No. of patients with diagnoses of SBB by DBE/total DBE performed
Fujimoto et al[28], 2007	64 (38-93)	45 M: 25 F: 20	Prospective study	Pillcam (Given Imaging, Yoqneam, Israel).	EN-450P5 DBE diagnostic model and/or the EN-450T5	CE: 12 h fast + 1 L sodium sulfate/sodium bicarbonate DBE: 72 h after CE in 36 pct	72 h	18/45 Angiodysplasia: 6 Varices: 2 jejunal	18/36
Hadithi et al[4], 2006	63.2 (19-86)	35 M:22 F: 13	Prospective blinded study	Given M2A, Given Imaging Ltd., Yoqneam, Israel	Fuji Photo Optical Incorporated Company Fujinon Inc., Japan	CE: fast overnight after the ingestion of 1 L of sodium sulfate/sodium bicarbonate solution DBE: fast overnight after ingestion of 1 L clean prep. for the antegrade approach and bowel cleansing as for colonoscopy (4 L Klean prep)	7 to 14 d	21/35 AVM: 19 Fresh blood and clots: 5	28/35 AVM: 16 Fresh blood and clots: 2
Hermans et al[11], 2017	69 (18-91)	146 M: 91 F: 55	Retrospective observational study.	Olympus VC (Olympus EndoCapsule; Tokyo, Japan) and Pillcam VC (Covidien plc, Dublin, Ireland)	Fujinon Double-Balloon Enteroscopy System (Fujinon GMBH, Germany), EN-450T5	CE: 2 L PEG in a single or split dose DBE: 1 L PEG divided into two doses to be used twice	111 (1–1091) days	105/134 Angiodysplasias: 70 active bleedings without visible focus : 35	93/146 Angiodysplasias: 19
Holleran et al[37], 2013	54 (16-90)	246 M: 130 F: 116	Retrospective comparative study	SB1 or SB2 pillcam (Given imaging, Yokneam, Israel)	Fujinon double-balloon enteroscope (EN-450P5/20, Fujinon, Inc., Saitama, Japan)	CE: No preparation was required other than an overnight fast. Anterograde DBE: overnight fast Retrograde DBE: PEG the day prior	NR*	40/46 Angiodysplasia: 10 Active bleeding: 3	116/246 Angiodysplasias: 44
Kaffes et al[34], 2007	62 ± 18	60	Prospective cohort study	M2A; Given Imaging Ltd, Yoqneam, Israel)	Fujinon	CE, DBE: fasting period of 8 h before the oral procedure and a bowel preparation with a sodium (Picoprep; Pharmatel, Thornleigh, Australia)	NR*	45/60 Angiectasia:28 Red spots: 9 Blood: 8	45/60 Angioectasia: 21 Red spots: 9 Blood: 8
Kalra, A et al[16], 2015	66.6 ± 13.2	116 M:65 F: 51	Retrospective review	Medtronic, Duluth, GA, the United States	Fujifilm Medical System, Stanford, CT, the United States	Retrograde DBE: bowel preparation the night before the procedure.	1 yr	/69	29/69 AVM: 29
Kamalaporn et al[30], 2008	64.1 (34-83)	195 M: 26 F:25	Retrospective review	Given M2A CE system (Given Imaging Ltd, Israel)	Fujinon DBE system (Fuji Photo Optical Incorporated Company, Fujinon Inc., Japan)	CE: 2 to 4 L PEG and fasted overnight, at least 8 h before the procedure DBE: 4 L PEG and fasted overnight	139 (40 to 335) d	181/202 studies Angiodysplasia: 33 Bleeding: 22	56/56 Angiodysplasia: 36 Bleeding: 9
Kameda et al[27], 2008	62.4 (27-84)	32 M: 13 F: 19	Prospective single-blind trial	Pill Cam capsule (M2A, Given Imaging, Yoqneam, Israel)	DBE system (FujinonToshiba ES System, Saitama, Japan)	CE: fasting after midnight on the evening before the examination (minimum 8 h) DBE: overnight fasting and ingestion of 1 l of electrolyte lavage preparation (Niflec, Ajinomoto Pharma, Tokyo, Japan) in the morning.	1-7 d	29/32 Angiodysplasia: 8 bleeding: 6	21/32 Angiodysplasia: 7 bleeding: 6
Li et al[35], 2010		190	Prospective study	M2A, Given Imaging, Ltd. (Yoqneam, Israel)	Fujinon EN-450P5/ 20 and EN-450P5/28 (Fujinon Inc., Saitama, Japan)	CE: 1 L of PEG electrolyte 12 h before the procedure Anterograde DBE: fasted for 8 h. Retrograde DBE: PEG electrolytes preparation 4 h before the examination	5.8 d (1-18)	165/190 AVM: 7 Fresh blood or clots: 8	34/51 AVM: 9 Bleeding: 0 Angioma: 4
Lin et al[40], 2007	63.5 ± 22.7 (11-87)	10 M:3 F:7	Prospective study	Pill Cam SB capsule (Given Imaging, Yoqneam, Israel)	DBE: EN- 450P5 and the EN-450T5	CE: fast overnight for 8-12 h Anterograde DBE: fasting for 6-8 h Retrograde DBE: bowel cleansing as in a colonoscopy.	7 d	9/10 Angiodysplasias: 3 Bleeding: 3	8/10 Angiodysplasias: 3 Varices: 1 Dieulafoy’s lesion: 1
Maeda et al[32], 2010	70 (30-92)	89 M: 48 F: 41	Retrospective analysis	PilCam SB® (SB1, SB2, or SB3) (Covidien, Irvine, CA, the United States).	(EN-450 T5/W or EN-580 T, Fujinon Inc., Saitama, Japan)	NR*	24 h	58/89 Angioectasia: 8 AVM : 3 Dieulafoy lesion: 9 Varices: 2	29/37 Angioectasia:8 AVM: 3 Dieulafoy lesion:6 Varice: 1
Marmo R et al[23], 2008	61.6 ± 16.2	193 M: 119 F: 74	Prospective study	Pillcam SB	Fujinon Double-Balloon Enteroscopy System	Anterograde DBE: fasting period of 8 h Retrograde DBE: 4 L PEG-based preparation	2 wk	175/193 Vascular lesions: 74 Blood or clot: 34	132/193 Vascular lesions: 72
Tian Min et al[39], 2013	55.4 (23-78)	62 M: 34 F:28	Prospective study	Pill Cam SB capsule	EN-450P5 and the EN-450T5 (Fujinon)	CE: 2 L to 4 L PEG and fasted overnight Anterograde DBE: fasting for 6-8 h before the procedure. Retrograde DBE: bowel cleansing as in a colonoscopy.	15 (4-60) d	44/62 Angiodysplasia: 26 Bleeding: 26	48/62 Angiodysplasia: 27 Bleeding: 30
Nakamura et al[29], 2006	58.5 (25 ± 85)	32 M: 21 F: 11	Prospective and blinded	M2A, Given Imaging,	Fuji EN−450 T5/20	CE: fluid diet for 12 h and observed a fasting period starting at midnight Anterograde DBE: fasted for 12 h Retrograde DBE: clear liquid diet on the day before the examination and PEG electrolyte lavage solution on the morning of the examination	48 h	19/32 Angiodysplasias: 4 Red spots: 2	12/28 Angiodysplasias: 2 Red spots: 2
Rahmi et al[33], 2013	67 ± 11	383 M: 114 F: 269	Prospective, multicenter study	PillCam SB device	EN-450P5 and EN-450T5; Fujinon	CE: residue-free diet 2 d before VCE ingestion; 2 L PEG solution the night before the examination; patients then fasted overnight Anterograde DBE: No bowel preparation Retrograde DBE: 4 L of a PEG solution was given the day before the procedure	4.1 ± 6.3 mo	266/383 Angiodysplasia: 266	205/266 Angiodysplasia: 190
Chu et al[17], 2016	51.1 ± 17.1	121 M: 60 F: 61	Study Cohorts	OMOM capsule endoscopic device (Jinshan Science and Technology Group Co., Ltd, Chongqing, China)	Fujinon EN-450P5/20	CE: 2 L polyethylene glycol-based electrolyte solution 12 h prior to the test, followed by an overnight fast for bowel preparation fast Retrograde DBE: bowel preparation used for CE procedure the day before the examination	1 wk	115/121 Angiodysplasia: 86% Active bleeding: 6	29/46 Angiodysplasia: 9
Zhang et al[15], 2015	47.19 (16-78)	88 M: 64 F: 24	Prospective study	Pill Cam SB	Fuji DBE system	CE: 3 liters of PEG (2 liters at 10:00 pm the night before the procedure, and 1 L with the simethicone at 4:00 am on the morning of the procedure) Anterograde DBE: fast for 6-8 h Retrograde DBE: 2 L of PEG	NR	53/88 MAV: 14 Hemangioma: 0 Diverticulum with a Bleeding: 1	52/88 MAV: 10 Hemangioma: 3 Diverticulum with a Bleeding: 7

M: Male; F: Female; SBB: Small bowel bleeding; PEG: Polyethylene glycol solution; AVM: Arteriovenous malformation; VC: Video capsule; NR: Not related; DBE: Double-balloon enteroscopy; VCE: Video capsule endoscope.