Efficacy and safety of double-balloon enteroscopy-assisted endoscopic retrograde cholangiopancreatography in surgically altered anatomy: A systematic review and meta-analysis

Table 1 Quality evaluation of the single-arm studies with JBI scale

Ref.	(1)	(2)	(3)	(4)	(5)	(6)	(7)	(8)	(9)	(10)
Aabakken et al[34]	Y	Y	Y	Y	N	Y	Y	Y	N	N
Emmett and Mallat[35]	Y	Y	Y	Y	N	Y	Y	Y	N	N
Maaser et al[36]	Y	Y	Y	Y	N	Y	Y	Y	N	N
Mönkemüller et al[37]	Y	Y	Y	Y	N	Y	Y	Y	N	N
Moreels et al[38]	Y	Y	Y	Y	N	Y	Y	Y	N	N
Pohl et al[39]	Y	Y	Y	Y	N	Y	Y	Y	N	N
Shimatani et al[25]	Y	Y	Y	Y	N	Y	Y	Y	N	Y
Parlak et al[40]	Y	Y	Y	Y	N	Y	Y	Y	N	N
Cho et al[41]	Y	Y	Y	Y	N	Y	Y	Y	N	N
Mönkemüller et al[42]	Y	Y	Y	Y	Y	Y	Y	Y	N	N
Raithel et al[43]	Y	Y	Y	Y	N	Y	Y	Y	N	N
Chua and Kaffes[44]	Y	Y	Y	Y	N	Y	Y	Y	N	N
Osoegawa et al[45]	Y	Y	Y	Y	N	Y	Y	Y	N	Y
Siddiqui et al[46]	Y	Y	Y	Y	N	Y	Y	Y	N	Y
Shah et al[8]	Y	Y	Y	Y	Y	Y	Y	Y	N	Y
Varabei et al[47]	Y	Y	Y	Y	N	Y	Y	Y	N	N
Sakakihara et al[48]	Y	Y	Y	Y	N	Y	Y	Y	N	Y
Tsutsumi et al[49]	Y	Y	Y	Y	N	Y	Y	Y	N	Y
De Koning and Moreels[6]	Y	Y	Y	Y	N	Y	Y	Y	N	Y
Shimatani et al[50]	Y	Y	Y	Y	Y	Y	Y	Y	N	Y
Shimatani et al[7]	Y	Y	Y	Y	N	Y	Y	Y	N	Y
Kashani et al[31]	Y	Y	Y	Y	N	Y	Y	Y	N	Y
Matsumoto et al[51]	Y	Y	Y	Y	N	Y	Y	Y	N	N
Nishio et al[52]	Y	Y	Y	Y	N	Y	Y	Y	N	Y
Sato et al[53]	Y	Y	Y	Y	N	Y	Y	Y	N	Y
Sirin and Hulagu[54]	Y	Y	Y	Y	N	Y	Y	Y	N	Y
Uchida et al[32]	Y	Y	Y	Y	N	Y	Y	Y	N	Y
CHENG et al[55]	Y	Y	Y	Y	N	Y	Y	Y	N	N
Obata et al[56]	Y	Y	Y	Y	N	Y	Y	Y	N	Y
Sato et al[57]	Y	Y	Y	Y	N	Y	Y	Y	N	Y

(1) Were there clear criteria for inclusion in the case series? (2) Was the condition measured in a standard, reliable way for all participants included in the case series? (3) Were valid methods used for identification of the condition for all participants included in the case series%? (4) Did the case series have consecutive inclusion of participants? (5) Did the case series have complete inclusion of participants? (6) Was there clear reporting of the demographics of the participants in the study? (7) Was there clear reporting of clinical information of the participants? (8) Were the outcomes or follow up results of cases clearly reported? (9) Was there clear reporting of the presenting site(s)/clinic(s) demographic information? (10) Was statistical analysis appropriate? Y: Yes; N: No.

Table 2 Quality evaluation of the eligible studies with Newcastle-Ottawa scale

Ref.	Selection	Comparability	Outcome
Cheng et al[26]	4	1	3
Tsou et al[58]	4	2	3
Tomoda et al[59]	4	2	2
Liu et al[60]	4	2	2
Tsutsumi et al[61]	4	1	2
Mizukawa et al[62]	4	2	3
Yamada et al[63]	4	2	3
Zamora Nava et al[64]	4	2	2
Farina et al[65]	4	2	3
Yokoyama et al[66]	4	2	2

Table 3 Patient characteristics

Ref.	Study design	Period	Country	n	Age	Female (%)	Patient anatomy	Inclusion criteria
Aabakken et al[34]	Retrospective case series	2005-2006	Norway	18 procedures in 13 patients	53 (2-81)	31	Roux-en-Y (n = 13)	Patients who underwent DBE-ERCP procedures with RY anatomy
Emmett and Mallat[35]	Retrospective case series	2005-2007	United States	20 procedures in 14 patients	47 (27-73)	50	RYGB (n = 6), PD (n = 4), Liver transplant with HJ (n = 1), Liver transplant with CJ (n = 1), PJ (n = 1), Frey procedure (n = 1)	Patients who had previously had a RYGI, RY Whipple resection with PJ, orthotropic liver transplantation with HJ or CJ, or a Frey procedure who underwent ERCP
Maaser et al[36]	Retrospective case series	2004-2007	Germany	11 procedures in 11 patients	62.8 (30-78)	27	Partial gastrectomy with GI and RY (n = 1), Partial gastrectomy with GI and RY and CD (n = 1), Total gastrectomy with RY (n = 1), Partial gastrectomy with Billroth II GI (n = 2), PD (n = 3), Pylorus-preserving CJ with RY (n = 2), RYHJ (n = 1), Duodenum-preserving pancreatic head resection in combination with CJ (n = 1)	Patients with various anatomic variations in whom DBE-ERCP was performed
Mönkemüller et al[37]	Prospective cohort study	-	Germany	11 procedures in 11 patients	59 (36-77)	9	RYHJ (n = 11)	Patients with RY anastomosis and pancreaticobiliary problems who underwent DBE-ERCP
Moreels et al[38]	Retrospective case series	2006-2008	Belgium	15 procedures	-	-	Roux-en-Y entero-enteric anastomosis	Patients who underwent DBE-ERCP for suspected pathology in the excluded gastrointestinal segment or in the biliopancreatic system after Roux-en-Y entero-enteric anastomosis
Pohl et al[39]	Retrospective case series	2004-2008	Germany	25 procedures in 15 patients	60.2 (25-80)	27	RYCJ (n = 15)	Patients with CJ anastomosis who underwent DBE-ERCP procedures
Shimatani et al[25]	Retrospective case series	2006-2008	Japan	68 procedures in 36 patients	-		RY total gastrectomy (n = 36), Billroth II gastrectomy (n = 17), PD (n = 15)	Patients with pancreaticobiliary disease and previous bowel reconstruction undergoing DBE-ERCP at a single center between January 2006 and December 2008
Parlak et al[40]	Retrospective case series	2006-2008	Turkey	14 procedures in 14 patients	45.3 (28-61)	54	RYHJ (n = 14)	Patients with RYHI who underwent ERCP
Cho et al[41]	Retrospective cohort study	2007-2008	Canada	29 procedures in 20 patients	57.9 (26-85)	50	RYHJ (n = 7), Billroth II (n = 6), RYGJ (n = 5), RYEJ (n = 1), PD with CJ (n = 1)	Patients with small-bowel reconstruction who underwent ERCP using a short DBE
Mönkemüller et al[42]	Retrospective case series	-	Germany	23 procedures in 18 patients	-	-	RYHJ (n = 18)	Patients who underwent DBE-ERCP procedures with Roux-en-Y hepaticojejunostomy
Raithel et al[43]	Prospective case series	2005-2008	Germany	86 procedures in 31 patients	61 (38-84)	54.8	Roux-en-Y reconstruction (n = 30), End-to-side gastrojejunostomy (n = 1)	Patients who underwent DBE-ERCP for pancreatobiliary diseases after complex abdominal anatomy (e.g., Billroth II, Whipple, Roux-en-Y)
Chua and Kaffes[44]	Retrospective case series	2008-2011	Australia	18 procedures in 16 patients	-	-	-	Patients who underwent DBE-ERCP procedures with surgically altered anatomy
Osoegawa et al[45]	Retrospective case series	2006-2011	Japan	47 procedures in 28 patients	74 (54-91)	35.7	Roux-en-Y total gastrectomy (n = 11), Billroth II gastrectomy (n = 15), Roux-en-Y anastomosis with PD (n = 2)	Patients who underwent DBE-ERCP for pancreatobiliary diseases after bowel reconstruction
Siddiqui et al[46]	Retrospective case series	2008-2011	United States	79 procedures in 79 patients	78 (29-86)	62	RYGB (n = 39), Billroth II (n = 3), PD (n = 20), HJ (n = 3), RYHJ (n = 4), RYGJ (n = 5), CJ (n = 2), RYPJ (n = 3)	Patients with various anatomic variations in whom ERCP was performed using short DBE
Shah et al[8]	Retrospective case series	2008-2009	United States	27 procedures in 27 patients	-	-	RYGB (n = 15), Non-RYGB including HJ, Whipple resection, other (n = 12)	Long-limb surgical bypass patients with suspected pancreatobiliary diseases
Varabei et al[47]	Retrospective case series	2009-2012	Belarus	33 procedures in 33 patients	53.7 (38-69)	76	RYHJ, jejunum loop with Braun bypass (n = NR)	Patients with RYHJ anastomoses and jejunum loop with Braun's bypass anastomosis who underwent DBE-ERCP
Cheng et al[26]	Retrospective cohort study	2006-2013	Taiwan	77 procedures in 77 patients	76 (50-95)	24	Billroth II (n = 77)	Patients with B2 gastrectomy in whom standard ERCP failed
Sakakihara et al[48]	Retrospective case series	2008-2012	Japan	44 procedures in 44 patients	63.5 ± 14.0	38.6	Modified Child’s method (n = 27) Roux-en Y reconstruction (n = 17)	Patients who underwent DBE-ERCP procedures with stenosis of choledochojejunal anastomosis
Tsou et al[58]	Retrospective cohort study	2007-2013	Taiwan	47 procedures in 47 patients	54.4 (26-87)	53	RY (n = 47)	Patients with RY anastomosis who underwent DBE-ERC
Tsutsumi et al[49]	Retrospective case series	2007-2013	Japan	72 procedures in 72 patients	69 (37-83)	39	PD (n = 72)	Patients with prior PD including SSPPD and PPPD who underwent attempted diagnostic or therapeutic ERCP
De Koning and Moreels[6]	Retrospective case series	2006-2012	Belgium	30 procedures in 10 patients	60 (30-76)	50	Short-limb RY (< 50 cm) with bilioenteric anastomosis (Whipple or BD) (n = 24), Short-limb RY (< 50 cm) with intact papilla (total gastrectomy) (n = 2), Long-limb RY (> 100 cm) with intact papilla (Scopinaro, GB) (n = 4)	Consecutive patients with RY altered small-bowel anatomy undergoing balloon-assisted ERCP performed by a single endoscopist in a single center
Shimatani et al[50]	Prospective case series	2013-2014	Japan	311 procedures in 311 patients	67.3 (14.6)	32.5	RY (n = 203), Billroth II (n = 26), PD (n = 44), PPPD (n = 31), Others (n = 7)	Consecutive patients above the age of 20 with altered GI anatomies and suspected biliary disease who were referred to eight institutions between June 2013 and May 2014
Tomoda et al[59]	Retrospective cohort study	2001-2014	Japan	20 procedures in 20 patients	50.85 (5-74)	35	RYHJ (n = 18), Not specified (n = 2)	Patients who underwent ERCP using a short DBE upon suspicion of biliary stricture after living donor liver transplantation with HJ reconstruction
Liu et al[60]	Retrospective cohort study	2009-2015	Australia	86 procedures in 52 patients	60.5 (18-89)	25	RYHJ (n = 42), RY with GJ (n = 9)	Patients with RY anastomosis who underwent a DBE-ERCP
Shimatani et al[7]	Retrospective case series	2015-2016	Japan	112 procedures in 100 patients	61.6 (18.2)	64.6	RYHJ (n = 30), RY partial gastrectomy (n = 17), RY total gastrectomy (n = 17), Billroth II gastrectomy (n = 8), PD (n = 13), PPPD (n = 12), Billroth II and RY (n = 1), GJ (n = 1), Jejunal pouch interposition (n = 1)	Procedures performed using new short-type DBE (N-short DBE) in postoperative patients at a single center between August 2015 and April 2016
Tsutsumi et al[61]	Prospective cohort study	2014-2017	Japan	33 procedures in 33 patients	65 (53-73)	56	RYHJ (n = 33)	Patients with suspected biliary diseases who had RYHI with side-to-end jejunojejunostomy
Kashani et al[31]	Retrospective case series	2005-2012	United States	129 procedures in 103 patients	50 (22-82)	87	RYGB (n = 103)	Patients with a history of RYGB who underwent DBE-ERCP
Matsumoto et al[51]	Retrospective case series	2010-2016	Japan	11 procedures in 11 patients	71 (53-74)	37	Child's reconstruction (n = 4) Roux-en-Y (n = 7)	Patients with HJ who underwent DBE-ERC for postoperative bile leakage
Mizukawa et al[62]	Retrospective cohort study	2008-2014	Japan	46 procedures in 46 patients	69 (64-75)	41	PD with Braun anastomosis (n = 29), PD without Braun anastomosis (n = 1), PPPD with Braun anastomosis (n = 12), SSPPD (n = 4)	Patients with suspected benign HJ anastomotic stricture after Whipple's procedure who underwent diagnostic ERCP using a short DBE
Yamada et al[63]	Prospective cohort study	2005-2017	Japan	326 procedures in 326 patients	64.9 (15.5) (EI-580BT cohort)	56	PD without Braun anastomosis (n = 1), PPPD with Braun anastomosis (n = 12), SSPPD (n = 4), Gastrectomy with Billroth II (n = 29), Gastrectomy with RY (n = 82), PD with Billroth II (n = 53), PD with RY (n = 42), RYHJ (n = 96), Liver transplantation with HJ (n = 20)	Patients with surgically altered anatomy that underwent ERCP using double-balloon endoscopy with the EI-580BT or EI-530B endoscope
Nishio et al[52]	Retrospective case series	2011-2018	Japan	104 procedures in 66 patients	70 (66.3-75.8) in the LO group; 67 (61-74) in the control group	44	Liver operation group: Hepatectomy (n = 14), and LDLT (n = 12), Control group: PD (n = 9), PPPD (n = 4), SSPPD (n = 27)	Patients who underwent DBE-ERCP after hepatectomy or LDLT (LO group); Patients who underwent DB-ERCP after pancreatoduodenectomy (control group)
Sato et al[53]	Retrospective case series	2008-2018	Japan	102 procedures in 102 patients	69 (22-84)	40	Roux-en-Y (n = 80), Billroth-II (n = 22)	Patients who underwent DBE-ERCP procedures with Roux-en-Y or Billroth-II for Hepaticojejunostomy anastomotic stricture
Sirin and Hulagu[54]	Retrospective case series	2008-2014	Japan	31 procedures in 31 patients	-	34	Billroth II with long afferenf limb (n = 8), Billroth II with acute angle of anastomosis of the afferent limb (n = 6), Billroth II with R-en-Y (n = 6), RYHJ (n = 11)	Patients with BII gastrojejunostomy and hepaticojejunostomy (with or without Roux-en-Y) who underwent DBE-ERCP during the same session due to failure of standard ERCP using standard duodenoscope
Uchida et al[32]	Retrospective case series	2011-2018	Japan	805 procedures in 319 patients	Median 69 years	38.9	Modified Child method after SSPPD (n = 133), modified Child method after PPPD (n = 29), Roux-en-Y with choledochojejunal anastomosis (n = 116), Roux-en-Y without choledochojejunal anastomosis (n = 19), Billroth II (n = 22)	Patients who underwent DBE-ERCP procedures with surgically altered gastrointestinal anatomy
Zamora Nava et al[64]	Prospective cohort study	2010-2016	Mexico	96 procedures in 75 patients	40.8 ± 10.2	71.9	RYHJ (n = 79), PD (n = 10), Billroth II (n = 3), Gastric bypass (n = 2), Esophagus jejunum anastomosis (Roux-en-Y) (n = 2)	Patients who underwent DBE-ERCP after Predominantly Roux-en-Y hepaticojejunostomy
CHENG et al[55]	Retrospective case series	2015-2020	Hong Kong SAR, China	46 procedures in 37 patients	70.8 ± 15.6	43.2	Billroth II (n = 15), Roux-en-Y (n = 10), RYHJ (n = 5), PD (n = 6), Portoenterostomy (Kasai Operation) (n = 1)	Patients who underwent DB-EERCP with biliary diseases
Obata et al[56]	Retrospective case series	2011-2020	Japan	79 procedures in 79 patients	79 (73-84)	22	Roux-en-Y Gastrectomy (n = 79)	Patients who underwent DB-EERCP procedures with Roux-en-Y for CBD stones
Sato et al[57]	Retrospective case series	2017-2019	Japan	20 procedures in 20 patients	73 (60-75)	45	PD with Billroth-II (n = 10), PD with Roux-en-Y (n = 4), Resection of the extrahepatic bile duct with Roux-en-Y (n = 5), Total pancreatectomy with Billroth-II (n = 1)	Patients who underwent DB-EERCP procedures with HJASs or who were unamenable to balloon dilation or prior plastic stent placement
Farina et al[65]	Retrospective cohort study	2013-2021	Italy	53 procedures in 53 patients	65 (23-89)	40	Pancreaticoduodenectomy (n = 9), Roux-en-Y gastrectomy (n = 17), Roux-en-Y biliodigestive anastomosis (n = 24), Billroth II gastrectomy (n = 3)	Patients who underwent DB-EERCP with post-surgical biliary disorders
Yokoyama et al[66]	Retrospective cohort study	2007-2022	Japan	289 procedures in 289 patients	-	-	RYG (TG) (n = 88), RYG (DG) (n = 33), Cardiac gastrectomy (n = 1), Billroth II (n = 33), RYHJ (n = 38), PD (n = 29), RYLT (n = 35)	Patients who underwent DB-EERCP procedures with SAA treated for biliary stones

ERCP: Endoscopic retrograde cholangiopancreatography; DBE-ERCP: Double-balloon enteroscopy-assisted endoscopic retrograde cholangiopancreatography; RYHJ: Roux-en-Y hepaticojejunostomy; RYGB: Roux-en-Y gastric bypass; RY: Roux-en-Y; HJ: Hepaticojejunostomy; CJ: Choledochojejunostomy; PJ: Pancreaticojejunostomy; GI: Gastrointestinal (or gastrojejunostomy); GJ: Gastrojejunostomy; CD: Choledochoduodenostomy; PD: Pancreaticoduodenectomy; RYCJ: Roux-en-Y choledochojejunostomy; RYEJ: Roux-en-Y esophagojejunostomy; RYGJ: Roux-en-Y gastrojejunostomy; RYPJ: Roux-en-Y pancreaticojejunostomy; RYGI: Roux-en-Y gastrointestinal reconstruction; PPPD: Pylorus-preserving pancreaticoduodenectomy; SSPPD: Subtotal stomach-preserving pancreaticoduodenectomy; LDLT: Living donor liver transplantation.

Table 4 Double-balloon enteroscopy-assisted endoscopic retrograde cholangiopancreatography characteristics

Ref.	Type of double balloon ERCP	Duration of procedure (minutes)	Indication for ERCP	Therapeutic intervention conducted
Aabakken et al[34]	Long (EN-450 T5, 200 cm)	40 (5-120)		Stent removal (n = 3)
Emmett and Mallat[35]	Long (200 cm)	99 (51-147)	Abnormal LFTs (n = 4), Acute pancreatitis (n = 1), Chronic pancreatitis (n = 2), Cholangitis (n = 2), Recurrent pancreaticobiliary pain (n = 5), Repeat procedure/follow-up (n = 6)	Stone extraction (n = 1), Biliary duct dilation (n = 1), Biliary duct sphincterotomy (n = 2), Biliary duct stent placement (n = 1), Pancreatic duct dilation (n = 1), Pancreatic duct sphincterotomy (n = 1), Pancreatic duct stent placement (n = 1), Pancreatic duct stent removal (n = 1)
Maaser et al[36]	Long (EN-450P5 or EN-450T5, 200 cm)		Choledocholithiasis (n = 1), Cholangitis (n = 4), Biliary pancreatitis (n = 1)	Sphincterotomy (n = 4), Stone extraction (n = 1), Dilation of anastomotic stricture (n = 1)
Mönkemüller et al[37]	Long (EN-450T5, 200 cm)	70 (45-120)	Jaundice (n = 2), Cholestasis (n = 6), Stent extraction (n = 1), CBD-stenosis (n = 1), Choledocolithiasis (n = 1)	Sphincterotomy (n = 2), papillectomy (n = 1), biliary stent insertion (n = 5), dilation of CBD stenosis with a balloon (n = 4), stone removal (n = 2), and stent retrieval (n = 5)
Moreels et al[38]	Long (EN-450T5, 200 cm)	-	Biliopancreatic pathology (15 procedures), unexplained abdominal pain after gastric bypass (9 procedures), suspected small bowel bleeding or abdominal pain after gastrectomy (4 procedures), enterocutaneous fistula closure (2 procedures)	For biliopancreatic pathology: Cholangiography, balloon dilation, stone extraction, stent placement for unexplained abdominal pain after gastric bypass: Gastric mucosa biopsy. For suspected small bowel bleeding or abdominal pain after gastrectomy: Enteroscopy and mucosal inspection. For enterocutaneous fistula closure: Closure using cyanoacrylate surgical glue and rotatable clip devices
Pohl et al[39]	Long (EN-450T5, 200 cm)	74.6 (49.6-99.6)	Evaluation of jaundice or suspected (n = 14), Biliary obstruction with pain considered to be of biliary origin (n = 1), Biliary obstruction with bleeding (n = 1)	Stone extraction (n = 5), Biliary duct dilation (n = 11), Biliary duct stent placement (n = 3)
Shimatani et al[25]	Short (EC-450BI5, 152 cm)	-	-	Stone extraction (n = 47), Nasobiliary drainage (n = 38), Stent placement (n = 36), Sphincterotomy (n = 31), Choledochojejunostomy dilation (n = 29), Tumor biopsy (n = 10), Nasopancreatic duct drainage (n = 1)
Parlak et al[40]	Long (EN-450T5, 200 cm)	75 (13-137)	Biliary obstruction (n = 11), Cholangitis (n = 9), Stent change (n = 7), Anastomotic stenosis on percutaneous Cholangiogram (n = 1), Jaundice (n = 2), Itching (n = 1)	Stent removal (n = 5), Extraction of catheter (n = 16), Stent placement (n = 10), Stent removal (n = 4), Balloon dilation (n = 1), Stricturoplasty with needle (n = 1)
Cho et al[41]	Short (EC-450BI5, 152 cm)	70.7 (30-117)	Choledocholithiasis (n = 10), Stricture (n = 8), Cholangitis (n = 8), Follow-up ERCP (n = 2), Bile leakage (n = 1)	Sphincterotomy (n = 7), Balloon dilation of biliary sphincter (n = 4), Stone extraction (n = 9), Biliary stricture dilation (n = 8), Stent placement (n = 9), Stent removal (n = 8)
Mönkemüller et al[42]	Long (EN-450T5, 200 cm)	70 (35-240)	Jaundice (n = 3) Cholestasis (n = 7) Choledocolithiasis (n = 4), Cholangitis (n = 3) Upper GI-bleeding (n = 1)	Biliary stent insertion, dilation of common bile duct stenosis with a balloon, stone removal with Dormia basket, stent retrieval
Raithel et al[43]	Long (EN-450T5, 200 cm)	-	Cholestasis, Cholangitis, Choledocholithiasis, Presence of a pancreatic pseudocyst, Suspected or advanced chronic pancreatitis	radiograph the bile ducts (n = 28) Radiography of the pancreatic duct (n = 1)
Chua and Kaffes[44]	Long (EN-450T5, 200 cm)	-	Biliary stenosis (n = 12) Choledocholithiasis (n = 3), Others (n = 1)	Stent removal, stricture dilatation, stone removal with a biliary extraction balloon, plastic stent insertion
Osoegawa et al[45]	Short (EC-450BI5, 152 cm)	93.6 ± 6.8	Pancreatobiliary diseases	Endoscopic biliary drainage (n = 24), Stone extraction (n = 14), Endoscopic sphincterotomy (n = 14), Balloon dilation (n = 10)
Siddiqui et al[46]	Short (EC-450BI5, 152 cm)		Removal of a previously placed stent (n = 5), Sphincter of Oddi dysfunction (n = 3), Surgical biliary leak (n = 3), Pancreatic anastomotic stricture (n = 2), suspected Choledocholithiasis (n = 48), Biliary strictures (n = 18)	Biliary sphincterotomy (n = 39), Dilation of CBD stenosis with a balloon (n = 30), Stent placement (n = 25), Stone extraction (n = 35), Brushing cytology of biliary strictures (n = 3), Stent removal (n = 4)
Shah et al[8]	Short (EC-450BI5, 152 cm); Long (EN-450T5, 200 cm)	(90-120)	Abnormal liver enzyme levels associated with abdominal pain and/or dilated bile ducts on non-invasive imaging (n = 62), Dilated bile ducts on imaging (n = 21), Cholangitis (n = 20), Abnormal liver enzyme levels (n = 11), Pancreatitis (n = 8), Other (n = 7)	Needle-knife precut papillotomy, free-hand (n = 19), Needle-knife precut over a pancreatic stent (n = 2), Needle-knife sphincterotomy over a biliary stent (n = 8), Pull-type sphincterotomy, biliary (n = 12), Pull-type sphincterotomy, pancreatic (n = 3), Anastomotic stricturoplasty in non-transplant hepaticojejunostomy (n = 10), Anastomotic stricturoplasty in transplant hepaticojejunostomy (n = 6), Papillary balloon dilation (n = 12), Stone extraction (1 pancreatic), (n = 21), Non-anastomotic stricture dilation (n = 16), Direct cholangioscopy (n = 11), Biliary stenting (n = 19), Pancreatic stenting (n = 6), Biliary stricture tissue sampling (n = 6)
Varabei et al[47]	Long (EN-450P, 200 cm)	85 (45-120)	Jaundice (n = NR), Cholestasis (n = NR), Cholangiolithiasis (n = NR), Recurrent cholangitis (n = NR), Strictures of HJA (n = NR)	Reconstructive re-operations on the biliary tract (n = 6), Laser vaporizations (n = 3), Stone extraction (n = 2), Lithotripsy (n = 1), Stone extraction and laser vaporization (n = 1)
Cheng et al[26]	Short (EC-450BI5, 152 cm) and Long (EN-450T5, 200 cm)	80 (60-120)	Cholangitis (n = 43), Choledocholithiasis (n = 9), Malignancy (n = 11), Pancreatitis (n = 6), Abnormal liver enzymes Dilated bile duct on imaging (n = 2)	Bile duct stone extraction (n = 49), Cystic duct stone extraction (n = 1), Malignant biliary stricture (n = 6), dilation (n = 9), Biliary dilation alone (n = 9)
Sakakihara et al[48]	Short (EC-450BI5, 152 cm)	-	Stenosis of choledochojejunal anastomosis	Balloon dilation and/or endoscopic biliary stenting
Tsou et al[58]	Short (EC-450BI5, 152 cm); Long (EN-450T5, 200 cm)	45.8 (10-141)	Choledocholithiasis (n = 35), Anastomotic stricture without stones (n = 6), Malignant obstruction (n = 6)	Endoscopic sphincterotomy (n = 4), Balloon dilation (n = 34), Stone extraction (n = 30), Stent placement (n = 10)
Tsutsumi et al[49]	Short (EC-450BI5 and EI-530B, 152 cm)	50 (9-167)		Balloon dilation (n = 47), Stone extraction (n = 17), Endoscopic biliary stenting (n = 18), Endoscopic nasobiliary drainage (n = 28), Peroral direct cholangioscopy (n = 9)
De Koning and Moreels[6]	Long (EN-450T5, 200 cm)	-	Cholangiogram	Biliary anastomosis balloon dilatation Sphincterotomy Precut sphincterotomy Sphincteroplasty Biliary stone removal Biliary plastic stent placement/removal Removal of surgical sutures at biliary anastomosis Treatment of biliary metallic stent ingrowth
Shimatani et al[50]	Short (EI-530B, 152 cm)	22.4 (± 20.8) to reach blind end56.3 (± 32.5) to complete ERC-related interventions	Cholangitis (n = 173), Hepatobiliary disorder without jaundice (n = 60), Obstructive jaundice (n = 43), Bile duct stones (n = 24), Hepatic abscess (n = 4), Others (n = 7)	-
Tomoda et al[59]	Short (EC-450BI5 and EI-530B, 152 cm)	75 (42-180)	Biliary atresia (n = 4), Liver cirrhosis (n = 10), Hepatocellular carcinoma (n = 3), Hepatitis B virus (n = 6), Hepatitis C virus (n = 4), Non-B and non-C hepatitis virus (n = 1), Primary sclerosing cholangitis (n = 1), Primary biliary cirrhosis (n = 2), Alagille syndrome (n = 1), Budd-Chiari syndrome (n = 1)	-
Liu et al[60]	Long (EN-450T5, 200 cm)	-	Biliary obstruction (n = 63), Cholestatic liver function tests (n = 41), Abnormal biliary imaging (n = 31), Ascending cholangitis (n = 14), Stent removal or replacement (n = 17), Bile leak (n = 3), Recurrent pancreatitis (n = 1), Biliary hemorrhage (n = 1), Other (n = 1)	Stent placement (n = 25), Stent removal (n = 11), Dilatation (n = 11), Biopsy/brushing (n = 1)
Shimatani et al[7]	Short (EI-580BT, 155 cm; EI-530B, 152 cm)	54 (37-73)	Bile duct stones (n = 28), Benign stenosis of hepatocyclic acid and hematologic angiogenesis (n = 24), Cholangitis (n = 21), Intrahepatic stones (n = 19), Obstructive jaundice (n = 12), Malignant stenosis of hepatocyclic acid and hematologic angiogenesis (n = 6), Others (n = 2)	Sphincterotomy, Dilation of hepatocyclic acid and hematologic angiogenesis, Stone extraction, Stent placement
Tsutsumi et al[61]	Short (EI-580BT, 155 cm; EI-530B, 152 cm); Long (EN-450T5, 200 cm)	89 (70-103)	Cholangitis (n = 20), Elevated hepatobiliary enzyme (n = 8), Liver abscess (n = 3), Hepatolithiasis (n = 2), Localized intrahepatic bile duct dilation (n = 1)	Stent placement (n = NR), Stone extraction (n = NR)
Kashani et al[31]	Long (450T5, 200 cm)	109 (93-109)	Sphincter of Oddi dysfunction (n = 66), Choledocholithiasis (n = 26), Pancreatitis (n = 9), Biliary stricture/obstruction (n = 8), Bile leak (n = 8), Cholangitis (n = 6), Abnormal liver tests (n = 5), Recurrent liver abscess (n = 1)	-
Matsumoto et al[51]	Short (EI-580BT, 155 cm; EI-530B, 152 cm)	62 (40-74)	Bile leakage (n = 11)	Treatment for bile leakage (drainage) (n = 11)
Mizukawa et al[62]	Short (EI-530B and EC-450BI5, 152 cm)	54 (37-82)	Benign hepatocyclic acid and hematologic angiogenesis structure (n = 52)	Biliary stone extraction (n = 12), Nasobiliary drainage (n = 38)
Yamada et al[63]	Short (EI-580BT, 155 cm; EI-530B, 152 cm)	55 (37-87), EI-580BT; 62 (41-88), EI-530B	Biliary strictures (n = 72), Anastomosis stenoses (n = 113), Choledocholithiasis (n = 94), Intrahepatic stone (n = 55), Miscellaneous (n = 11)	Biliary stone extraction (n = 148), Biliary plastic stenting (n = 101), Biliary metallic stenting (n = 20), Balloon dilation of biliary anastomotic stricture (n = 106), Endoscopic papillary balloon dilation (n = 59), Endoscopic papillary large balloon dilation (n = 24), Endoscopic nasobiliary drainage (n = 151), Pancreatic stone extraction (n = 9), Pancreatic plastic stenting (n = 18), Balloon dilation of pancreatic anastomotic stricture (n = 14), Endoscopic nasopancreatic drainage (n = 16)
Nishio et al[52]	Short (EI-580BT, 155 cm; EI-530B, 152 cm)	43.5 (28.3-61.5) in LO group vs 30 (21-44) in control group	Stenosis of hepaticojejunostomy, bile duct stones, cholangitis, stenosis of biliary duct and others	Balloon dilation, stone extraction, stent placement
Sato et al[53]	Short (EI-580BT, 155 cm; EI-530B and EC-450BI5, 152 cm)	70 (15-240)	Hepaticojejunostomy anastomotic stricture	Balloon dilation and Balloon dilation + plastic stent placement
Sirin and Hulagu[54]	Long (EN-450T5, 200 cm)	-	Biliary stone (n = 15), Stenosis (n = 3), Cholestasis (n = 1), painless jaundice (n = 3), Pancreatic head tumor (n = 3), biliary duct dilatation (n = 3), Cholangiocarcinoma (n = 3)	Extraction of biliary stone by balloon, dilation of stenosis, sphincterotomy and extraction of biliary stone by balloon, biliary stenting, sphincterotomy
Uchida et al[32]	Short (EI-580BT, 155 cm; EI-530B and EC-450BI5, 152 cm)	Median 60	Choledochojejunal anastomosis stenosis (443 procedures), bile duct stones (126 procedures), biliary stricture (177 procedures), pancreatic indications (56 procedures), others (3 procedures)	Plastic stent placement for stenosis, complete stone removal for bile duct stones, diagnostic ERCP
Zamora Nava et al[64]	Long (EN-450T5 and EN-580T, 200 cm); Short (EC-450BI5, 152 cm)	-	Mainly cholangitis (49%), other indications include cholestatic pattern in liver function tests, documented stenosis of hepaticojejunostomy, or lithiasis by imaging studies (CT or MRCP)	Dilation (94.6%), stone extraction (78.6%), sphincterotomy/precut (10.7%), stent placement (7.1%), lithotripsy (1.8%)
CHENG et al[55]	Short (EI-580BT, 155 cm)	115.8 (40-275)	Bile duct stone (40.5%), painless obstructive jaundice (40.5%), acute cholangitis (13.5%), acute pancreatitis (5.5%)	Stone extraction or mechanical lithotripsy (n = 23), Sphincterotomy/sphincteroplasty (n = 18), Stricture dilatation (n = 7), Plastic stent insertion (n = 11), Metallic stent insertion (n = 6), Biopsy/brush cytology (n = 4)
Obata et al[56]	Short (EI-580BT, 155 cm; EI-530B, 152 cm)	90 (67-120)	CBD stones	Precut alone 4 (n = 6), EST alone 6 (n = 10), EPBD alone 9 (n = 14), EPLBD alone 5 (n = 8), Precut + EPBD 12 (n = 19), Precut + EPLBD 5 (n = 8), EST + EPBD 12 (n = 19), EST + EPLBD 5 (n = 8), None 5 (n = 8)
Sato et al[57]	Short (EI-580BT, 155 cm)	63 (35-86)	Treatment of hepaticojejunostomy anastomotic strictures	Placement of fully-covered metal stent (FCSEMS) for HJASs; balloon dilation of stricture prior to stent placement; additional plastic stent placement in some cases as “rescue stent”
Farina et al[65]	Short (EI-580BT, 155 cm); Long (EN580T, 200 cm)	-	Cholangitis or jaundice caused by benign/malignant biliary stenosis of the common bile duct or stenosis of a biliodigestive anastomosis, common bile duct gallstones, biliary leak, and removal of previously placed stents	Sphincterotomy, stone extraction, or pancreaticobiliary stent placement
Yokoyama et al[66]	Short (EI-580BT, 155 cm; EI-530B and EC-450BI5, 152 cm); Long (EN-450P5 and EN-450T5, 200 cm)	96 ± 43	Biliary stone	Stone extraction (n = 257)

CBD: Common bile duct; ERCP: Endoscopic retrograde cholangiopancreatography; LFT: Liver function tests; CT: Computed tomography; ERC: Endoscopic retrograde cholangiography; EST: Endoscopic sphincterotomy; EPBD: Endoscopic papillary balloon dilation; EPLBD: Endoscopic papillary large balloon dilation.

Table 5 Double-balloon enteroscopy-assisted endoscopic retrograde cholangiopancreatography outcomes

Ref.	Anastomosis/papilla reached, % (n/N)	Enteroscopy success, % (n/N)	Diagnostic success, % (n/N)	Procedural success, % (n/N)	Adverse events, % (n/N)	Adverse event description
Aabakken et al[34]	94 (17/18)	83.3 (15/18)	100 (15/15)	100 (9/9)	0 (0/16)	-
Emmett and Mallat[35]	85 (17/20)	94.1 (16/17)	-	100 (10/10)	0 (0/20)	-
Maaser et al[36]	72.7 (8/11)	64 (7/11)	64 (7/11)	100 (5/5)	0 (0/11)	-
Mönkemüller et al[37]	90.9 (10/11)	90.9 (10/11)	81.81 (9/11)	60 (6/10)	9.09 (1/11)	Perforation of hepatocolejunostomy during balloon dilatation (n = 1)
Moreels et al[38]	86.7 (13/15)	80 (12/15)	80 (12/15)	80 (12/15)	13.3 (2/15)	Perforation (n = 2)
Pohl et al[39]	84 (22/25)	84 (22/25)	-	100 (16/16)	0 (0/15)	-
Shimatani et al[25]	97 (100/103)	-	98 (98/100)	100 (98/98)	5 (5/103)	Retroperitoneal emphysema (n = 1), Intestinal perforation (n = 1), Retroperitoneal perforation (n = 1), Post-endoscopic sphincterotomy perforation (n = 1), Subcutaneous emphysema with pneumothorax (n = 1)
Parlak et al[40]	92.86 (13/14)	92.86 (13/14)	92.86 (13/14)	85.71 (12/14)	7.14 (1/14)	Perforation (n = 1)
Cho et al[41]	86.2 (25/29)	82.76 (24/29)	83 (16/20)	100 (24/24)	0 (0/20)	-
Mönkemüller et al[42]	-	77.8 (14/18)	92.9 (13/14)	69.2 (9/13)	5.6 (1/18)	Perforation (n = 1)
Raithel et al[43]	74.2 (23/31)	-	-	87.2 (75/86)	5.8 (5/86)	Post-ERCP pancreatitis (n = 2), Post-interventional bleeding (n = 1), Perforation (n = 2)
Chua and Kaffes[44]	-	77.8 (14/18)	77.8 (14/18)	80 (8/10)	-	-
Osoegawa et al[45]	95.7 (45/47)	88.9 (40/45)	88.9 (40/45)	100 (40/40)	2.1 (1/47)	Perforation (n = 1)
Siddiqui et al[46]	89.9 (71/79)	90.1 (64/71)	90.1 (64/71)	100 (64/64)	5.1 (4/79)	Mild post-ERCP pancreatitis (n = 3), Self-limited bleeding (n = 1)
Shah et al[8]	74 (20/27)	-	-	63 (17/27)	-	Pancreatitis (n = 5), Mild bleeding (n = 1), Abdominal pain requiring hospital admit (n = 3), Throat pain requiring physician contact (n = 4), Perforation (n = 2), Death (n = 1), Reported for all interventions including SBE, DBE, and rotational ERCP
Varabei et al[47]	63.6 (21/33)	63.6 (21/33)	61.9 (20/33)	57.14 (12/21)	-	-
Cheng et al[26]	95 (73/77)	89.61 (69/77)	-	87 (67/77)	6.5 (5/77)	Minor perforation (n = 2), Mucosal tear (n = 2), Intestinal perforation (n = 1)
Sakakihara et al[48]	86.4 (38/44)	-	-	81.8 (36/44)	15.9 (7/44)	Cholangitis (n = 7)
Tsou et al[58]	83 (39/47)	94.9 (37/39)	94.9 (37/39)	100 (37/37)	4.3 (2/47)	Intestinal perforation (n = 1), Biliary tract infection (n = 1)
Tsutsumi et al[49]	98.61 (71/72)	98.61 (71/72)	98.61 (71/72)	100 (59/59)	2.72 (2/72)	Cholangitis (n = 2)
De Koning and Moreels[6]	-	-	-	73 (22/30)	10 (3/30)	Retroperitoneal free air (n = 3), Post-ERCP cholangitis (n = 2), Post-ERCP pancreatitis (n = 2), Liver capsule dehiscence (n = 1), (List includes complications for both DBE and SBE procedures in study)
Shimatani et al[50]	97.7 (304/311)	-	96.4 (293/304)	97.9 (277/283)	10.6 (33/311)	Obvious perforation (n = 1), Microperforation (n = 6), Mucosal laceration (n = 1), Biliary damage (n = 4), Pancreatitis (n = 11), Cholangitis (n = 8), Aspiration pneumonia (n = 2)
Tomoda et al[59]	85 (17/20)	85 (17/20)	70 (14/20)	55 (11/20)	10 (2/20)	Bleeding (n = 1), Ischemic liver graft (n = 1)
Liu et al[60]	76 (65/86)	70 (60/86)	100 (1/1)	89.4 (42/47)	2.33 (2/86)	Post-procedure cholangitis (n = 1), Aspiration pneumonia (n = 1)
Shimatani et al[7]	99.1 (111/112)	-	98.2 (109/111)	100 (109/109)	2.7 (3/112)	Laceration in intestinal tract (n = 3)
Tsutsumi et al[61]	97 (32/33; 30/33 short DBE, 2/33 Long DBE)	97 (32/33; 30/33 short DBE, 2/33 Long DBE)	81 (26/32; 21/32 short DBE, 5/32 Long DBE)	-	18.18 (6/33)	Perforation and pneumatosis (n = 3), Cholangitis (n = 1), Elevated hepatobiliary enzymes (n = 1), Mucosal laceration of ilium (n = 1)
Kashani et al[31]	93.8 (121/129)	94.57 (87/92)	-	94.57 (87/92)	10.1 (13/129)	Pancreatitis (n = 10), Cholangitis (n = 1), Perforation (n = 2)
Matsumoto et al[51]	100 (11/11)	100 (11/11)	-	63.6 (7/11)	0 (0/11)	-
Mizukawa et al[62]	100 (46/46)	100 (46/46)	100 (46/46)	100 (46/46)	6.52 (3/46)	Cholangitis (n = 3)
Yamada et al[63]	EI-580BT: 100 (163/163) EI-530B: 100 (163/163) Cumulative: 100 (326/326)	EI-580BT: 96 EI-530B: 87 Cumulative: 91.5	-	EI-580BT: 92 (150/163) EI-530B: 89 (145/163) Cumulative: 90.5 (295/326)	EI-580BT: 4.3 (7/163) EI-530B: 6.7 (11/163) Cumulative: 5.5 (18/326)	Pancreatitis (n = 11), Perforation (n = 7)
Nishio et al[52]	95.2 (99/104)	84.5 (81/97)	93.8 (91/97)	97.4 (75/77)	8.7 (9/104)	Cholangitis (n = 5), pancreatitis (n = 2), bleeding (n = 2)
Sato et al[53]	-	-	-	89.2 (91/102)	17.6 (18/102)	Cholangitis (n = 10), Intra-abdominal/retroperitoneal air (n = 6), Bile leakage (n = 1), Bleeding (n = 1)
Sirin and Hulagu[54]	96.8 (30/31)	96.8 (30/31)	87.1 (27/31)	87.1 (27/31)	6 (2/31)	Perforation (n = 1), Retroperitoneal abscess (n = 1)
Uchida et al[32]	94.3 (759/805)	-	-	90.7 (730/805)	5.5 (44/805)	Cholangitis (n = 20) pancreatitis (n = 14), intestinal perforation (n = 6), others (4 cases, including 2 biliary leakage, 1 pancreatic leakage caused by guidewires, and 1 pneumothorax)
Zamora Nava et al[64]	-	77.1 (74/96)	69.8 (67/96)	83.6 (56/67)	14.5 (14/96)	Cholangitis (n = 7), Pancreatitis (n = 2), Perforation (n = 2), Mucosal tear (n = 2), Hemorrhage (n = 1)
CHENG et al[55]	95.7 (44/46)	-	84.1 (37/44)	76.1 (35/46)	13 (6/46)	Intestinal perforation (n = 2), acute cholangitis (n = 3), acute pancreatitis (n = 1)
Obata et al[56]	92.4 (73/79)	81 (64/79)	80 (63/79)	78 (62/79)	5 (4/79)	Bowel perforation (n = 2), pancreatitis (n = 1), hypoxia (n = 1)
Sato et al[57]	100 (20/20)	100 (20/20)	100 (20/20)	100 (20/20)	-	-
Farina et al[65]	69.8 (37/53)	31/37 (83.8)	-	31/37 (84)	0 (0/53)	-
Yokoyama et al[66]	91.3 (264/289)	83.4 (241/289)	-	100 (241/241)	-	-

ERCP: Endoscopic retrograde cholangiopancreatography; DBE: Double-balloon enteroscopy.

Table 6 Summary of proportion meta-analysis of all outcomes (after excluding the 7 studies that used both short-scope and long-scope double-balloon enteroscopy)

Type of DBE	Papilla reached (%)	Enteroscopy success (%)	Diagnostic success (%)	Procedural success (%)	Adverse events (%)
Overall	94 (95%CI: 90-96), I2 = 83.6	89 (95%CI: 84-93), I2 = 74.9	92 (95%CI: 86-96), I2 = 80.9	93 (95%CI: 88-96), I2 = 85.5	5.5 (95%CI: 4-7.2), I2 = 45.0
Short DBE	97 (95%CI: 94-99), I2 = 79.6	92 (95%CI: 86-97), I2 = 74.0	94 (95%CI: 88-98), I2 = 80.2	89 (95%CI: 89-99), I2 = 89.6	6.2 (95%CI: 4.1-8.6), I2 = 59.9
Long DBE	86 (95%CI: 78-92), I2 = 67.2	84 (95%CI: 76-91), I2 = 69.5	87 (95%CI: 74-96), I2 = 80.4	87 (95%CI: 79-94), I2 = 62.5	4.5 (95%CI: 2.2-7.4), I2 = 6.7
Test for subgroup differences P value	P < 0.0001	P = 0.0289	P = 0.1249	P = 0.0275	P = 0.7069

DBE: Double-balloon enteroscopy.