Post-endoscopic retrograde cholangiopancreatography pancreatitis: A systematic review for prevention and treatment

Table 1 Patient-related risk factors

Definite	Possible	No risk
Young age	Absence of CBD stone	Normal/small CBD diameter
Female gender	Normal serum bilirubin	Pancreas divisum
Suspected SOD	Periampullary diverticulum	Allergy to contrast medium
Recurrent pancreatitis
Absence of chronic pancreatitis
History of previous PEP

Adapted from Guda et al[9], Cotton et al[30], Cotton[41], and Srinivasan et al[54]. CBD: Common bile duct; SOD: Sphincter of Oddi dysfunction; PEP: Post-endoscopic retrograde cholangiopancreatography pancreatitis.

Table 2 Brief contents of reviewed articles on rectal indomethacin

Authors	Year	Country	n	Intervention	Design	Incidence of PEP1				P value
						Study group		Control (compared)
Elmunzer et al[60]	2012	United States	602	2 × 50-mg indomethacin or 2 × placebo right after ERCP	Prospective, multicenter, placebo-controlled, double-blind	27/295 (9.2%) [IND]		52/307 (16.9%) [Placebo]		0.005
Döbrönte et al[65]	2014	Hungary	665	100 mg indometha-cin or an placebo 10-15 min prior to ERCP	Prospective, multicenter, placebo- controlled	20/347 (5.76%) [IND]		22/318 (6.92%) [Placebo]		0.541
Patai et al[61]	2015	Hungary	539	100 mg indomethacin or placebo 1 h prior to ERCP	Prospective, single center, placebo-controlled, double-blind	18/270 (6.7%) [IND]		37/269 (13.8%) [Placebo]		0.406
Andrade-Davila et al[56]	2015	Mexico	166	100 mg of indomethacin or 2.6 g suppository of glycerin right after ERCP	Prospective, single center, placebo-controlled	4/82 (4.87%) [IND]		17/84 (20.23%) [GS]		0.01
Luo et al[62]	2016	China	2600	100 mg indomethacin for unselected patients within 30 min prior to ERCP or 100 mg indomethacin just after ERCP for patients with high risks	Prospective, multicenter, single-blind	47/1297 (4%) [Universal IND]		100/1303 (8%) [Risk-stratified IND]		< 0.001
Levenick et al[58]	2016	United States	449	100 mg indomethacin or placebo during ERCP	Prospective, single center, double-blind, placebo-controlled	16/223 (7.2%) [IND]		11/226 (4.9%) [Placebo]		0.33
Hosseini et al[63]	2016	Iran	406	100 mg indomethacin two hours before the ERCP or 1 L of ISP within 2 h before ERCP and 2 L within 16 h after ERCP or indomethacin and ISP or 2 g of glycerin in suppositories	Prospective, single center, blinded subject data	11/100 (11%) [IND]	10/100 (10%) [ISP]	0/101 (0) [IND+ISP]	17/105 (16%) [RG]	-
Mok et al[64]	2017	United States	192	LR + IND, NS + IND, LR + placebo or NS + placebo	Prospective, single center, double-blind, placebo-controlled	3/48 (6%) [LR+IND]	6/48 (13%) [NS+IND]	9/48 (19%) [LR+Placebo]	10/48 (21%) [NS+Placebo]	0.04

¹The fractional ratios are “Number of PEP incidences/number of patients in the group”. Rate of PEP incidences are given in the parenthesis. Definitions of the procedures applied to groups are given in the brackets. n: Number of patients (sample size); IND: Indomethacin; ISP: Intravenous (IV) saline perfusion; RG: Rectal glycerin; LR: Lactated ringer’s solution; NS: Standard normal saline solution; GS: Glycerin suppository.

Table 3 Brief contents of reviewed articles on pharmacological agents

Agent	Authors	Year	Country	n	Design	Incidence of PEP1			P value
						Study group		Control (or compared)
Intraduodenal Acetic Acid (IAA)	Fang et al[97]	2018	China	210	Prospective, single center, double-blind	8/105 (7.6%) [IAA]		11 /105 (10.5%) [Saline]	0.47
Celecoxib	Kato et al[77]	2017	Japan	170	Prospective, single center	10/85 (11.7%) [Celecoxib]		13/85 (15.3%) [Saline]	0.65
Raw Rhubarb Solution (RRS)	Wang et al[133]	2017	China	500	Prospective, single center	5/250 (2%) [RRS]		19/250 (7.6%) [Water]	0.003
Nitroglycerin + Glucagon	Katsinelos et al[106]	2017	Greece	455	Prospective, single center, double–blind	7/227 (3.08%) [Nitroglycerin + glucagon]		17/228 (7.46%) [HBW]	0.037
Ketoprofen	Onofrio et al[73]	2017	Brazil	477	Prospective, single center, double-blind, placebo-controlled	5/224 (2.2 %) [Ketoprofen]		5/253 (2 %) [Placebo]	1.0
Vigorous IVFR	Choi et al[87]	2017	South Korea	510	Prospective, multi center, double-blind	11/255 (4.3%) [Vigorous IVFR]		25/255 (9.8%) [StandartIVFR]	0.016
Aggressive Hydration with Lactated Ringer’s Solution (AHLRS)	Buxbaum et al[83]	2014	United States	71	Prospective, multicenter, controlled	0/39 (0%) [AHLRS]		4/23 (17%) [SHLRS]	0.016
Udenafil+Aceclofenac	Lee et al[109]	2015	South Korea	216	Prospective, multicenter, double-blind, placebo-controlled	17/107 (15.8%) [Udenafil+Aceclofenac]		18/109 (16.5%) [Placebo]	0.901
Somatostatin	Bai et al[127]	2015	China	900	Prospective, multicenter, open-label	18/445 (4 %) [Somatostatin]		34/455 (7.5 %) [No Somatostatin]	0.03
	Concepcion-Martin et al[129]	2014	Spain	510	Prospective, single-center, placebo-controlled, double-blind	19/255 (7.5 %) [Somatostatin]		17/255 (6.7 %) [Placebo]	0.73
	Wang et al[130]	2013	China	124	Prospective, single-center, placebo-controlled	6/36 (16.7%) [Pre-ERCP somatostatin]	5/47 (10.6%) [Post-ERCP somatostatin]	6/41 (14.6%) [Placebo]	0.715
Intramuscular Diclofenac	Park et al[66]	2015	South Korea	343	Prospective, single center, double-blind, placebo-controlled	22/173 (12.7 %) [Intramuscular Diclofenac]		20/170 (11.8 %) [Placebo]	0.87
Rectal Diclofenac	Otsuka et al[68]	2012	Japan	104	Prospective, multicenter, controlled	2/51 (3.9%) [Diclofenac with Saline]		10/53 (18.9%) [Saline]	0.017
Nafamostat Mesilate (NM)	Kim et al[118]	2016	South Korea	382	Prospective, single center, comparative	5/179 (2.8%) [NM - 24 hour infusion]		4/192 (2.1%) [NM - 6 hour infusion]	0.744
	Ohuchida et al[114]	2015	Japan	809	Prospective, single center, double-blind	14/405 (3.5) [NM]		27/404 (6.7) [Glucose Solution]	0.035
	Park et al[115]	2011	South Korea	595	Prospective, single-center, controlled	8/198 (4%) [20 mg of NM]	10/197 (5.1%) [50 mg of NM]	26/200 (13%) [Dextrose]	< 0.0001
	Yoo et al[117]	2011	South Korea	286	Prospective, single-center, double-blind, placebo controlled	4/143 (2.8%) [NM]		13/143 (9.1%) [Dextrose Solution]	0.03
	Choi et al[116]	2009	South Korea	704	Prospective, single-center, double-blind, controlled	12/354 (3.3%) [NM]		26/350 (7.4%) [Dextrose Solution]	0.018
Ulinastatin + Nafamostat	Park et al[121]	2014	South Korea	159	Prospective, single center, placebo-controlled	1/53 (1.9%) [Ulinastatin]	2/53 (3.8%) [Nafamotat]	7/53 (13.2) [Placebo]	0.037
Risperidone + Ulinastatin	Tsujino et al[125]	2013	Japan	226	Prospective, multicenter, placebo-controlled	6/113 (5.3%) [Risperidone + Ulinastatin]		10/113 (8.8 %,) [Ulinastatin]	0.438
Udenafil	Oh et al[107]	2011	South Korea	278	Prospective, multicenter, double-blind, placebo-controlled	11/137 (8.0%) [Udenafil]		11/141 (7.8%) [Placebo]	944
Allopurinol	Abbasinazari et al[135]	2011	Iran	74	Prospective, single-center, double-blind, placebo-controlled	3/29 (10,4%) [Allopurinol]		5/45 (11,1%) [Placebo]	0.97
Neurokinin-1 receptor antagonist (Aprepitant)	Shah et al[136]	2012	United States	73	Prospective, single-center, double-blind, placebo-controlled	7/34 (20.6%) [Aprepitant]		7/39 (17.9%) [Placebo]	1.0
Secretin	Jowell et al[96]	2011	United States	869	Prospective, single-center, double-blind, placebo controlled	36/413 (8.7%) [Secretin]		65/431 (15.1%) [Placebo]	0.004
Epinephrine	Xu et al[143]	2011	China	941	Prospective, single-center, placebo controlled	9/461 (1.95%) [Epinephrine]		31/480 (6.45%) [Saline]	0.0086
Valdecoxib and GlycerylTrinitrate (GTN)	Bhatia et al[70]	2011	India	371	Prospective, single-center, controlled	12/121 (9.9%) [Valdecoxib]	12/124 (9.7%) [GTN]	13/126 (10.3%) [No intervention]	0.986
Glyceryl Nitrate	Nøjgaard et al[100]	2009	Multi Country	806	Prospective, multicenter, double-blind, placebo-controlled	18/401 (4.5%) [Glyceryl Nitrate]		29/405 (7.1%) [Placebo]	0.11
Platelet Activating Factor (PAF)	Sherman et al[91]	2009	United States	600	Prospective, multicenter, double-blind, placebo-controlled	35/200 (17.5%) [PAF 1 mg/kg]	32/201 (15.9%) [PAF 5 mg/kg]	39/199 (19.6%) [Placebo]	0.59
Interleukin-10 (IL-10)	Sherman et al[88]	2009	Multi Country	305	Prospective, multicenter, double-blind, placebo-controlled	14/91 (15.4%) [IL-10 8 µg/kg]	24/109 (22%) [IL-10 20 µg/kg]	15/105 (14.3%) [Placebo]	0.83 0.14

¹The fractional ratios are “Number of PEP incidences/number of patients in the group”. Rate of PEP incidences are given in the parenthesis. Definitions of the procedures applied to groups are given in the brackets. HBW: Hyoscine n-butyl plus sterile water; IVFR: Intravenous fluid resuscitation; SHLRS: Standart hydration with lactated ringer’s solution.

Table 4 Brief contents of reviewed articles on procedural techniques

Proce-dure	Authors	Year	Country	n	Design	Incidence of PEP1						P value
						Study group			Control (or compared)
Endosco-pic Nasobilia-ry Drainage (ENBD)	Huang et al[150]	2018	China	155	Prospec-tive, single center	1/78 (1.28%) [ENBD]			8/77 (10.4%) [No ENBD]			0.018
	Xu et al[145]	2015	China	218	Prospec-tive, single center	0/41 (0%) [ENBD +EPBD]	2/34 (5.9%) [ENBD +EST]	5/38 (13.2%) [Only ENBD]	6/36(16.7%) [EPBD]	3/39 (7.7%) [EST]	2/30(6.7%) [Neither]	-
Wire-Guided Biliary Cannula-tion (WGC)	Kobayashi et al[158]	2013	Japan	322	Prospec-tive, multicen-ter, controlled	10/163 (6.1%) [WGC]			10/159 (6.3%) [CC]			0.95
	Lee et al[161]	2009	South Korea	300	Prospec-tive, single center	3/150 (2%) [WGC]			17/150 (11.3%)) [CC]			0.001
	Bassan et al[162]	2018	Asia Pacific Region	707	Prospec-tive, multicen-ter, single-blinded	NA/355 (9.3%) [0.035-inch wire]			NA/357 (7.8%) [0.025-inch wire]			0.51
Pancrea-tic Stent Place-ment (PSP)	Fujisawa et al[156]	2016	Japan	200	Prospec-tive, single center	2/98 (2%) [PSP 3 cm]			9/102 (8.8%) [PSP 5 cm]			0.035
	Conigliaro et al[157]	2013	Italy	40	Prospec-tive, multicen-ter, blinded	6/21 (29 %) [Immediate stent removal]			0/19 [leaving the stent]			0.021
	Lee et al[151]	2012	South Korea	101	Prospec-tive, multicen-ter,	6/50 (12%) [3F PSP]			15/51 (29.4) [Nonstent]			0.031
	Sofuni et al[152]	2011	Japan	407	Prospec-tive, multicen-ter	16/203 (7.9%) (PSP)			31/204 (15.2%) [Nonstent]			0.021
	Pan et al[153]	2011	China	40	Prospec-tive, single center	4/20 (20%) [PSP]			14/20 (70%) [Nonstent]			< 0.01
	Ito et al[154]	2010	Japan	70	Prospec-tive, single center	0/35 (0%) [PSP]			9/35 (24%) [Nonstent]			< 0.01
	Kawagu-chi et al[155]	2012	Japan	120	Prospec-tive, single center	1/60 (1.7%) [PSP]			8/60 (13.3%) [Nonstent]			0.0322
Needle Knife Sphincter-otomy (NKS)	Swan et al[164]	2013	Australia	73	Prospec-tive, single center, single blind	8/39 (20.5%) [NKS]			6/34 (17.6%) [CSC]			1.0

¹The fractional ratios indicates “Number of PEP incidences/number of patients in the group”. Rate of PEP incidences are given in the parenthesis. Definitions of the procedures applied to groups are given in the brackets. n: Number of patients (sample size); EPBD: Endoscopic papillary balloon dilatation; CC: Conventional cannulation; EST: Endoscopic sphincterotomy; CSC: Continued standart cannulation.