Prospective Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Endosc. Nov 16, 2016; 8(19): 709-715
Published online Nov 16, 2016. doi: 10.4253/wjge.v8.i19.709
Post-endoscopic retrograde cholangiopancreatography pancreatitis: Risk factors and predictors of severity
Ayman El Nakeeb, Ehab El Hanafy, Tarek Salah, Ehab Atef, Hosam Hamed, Ahmad M Sultan, Emad Hamdy, Mohamed Said, Ahmed A El Geidie, Tharwat Kandil, Mohamed El Shobari, Gamal El Ebidy
Ayman El Nakeeb, Ehab El Hanafy, Tarek Salah, Ehab Atef, Hosam Hamed, Ahmad M Sultan, Emad Hamdy, Mohamed Said, Ahmed A El Geidie, Tharwat Kandil, Mohamed El Shobari, Gamal El Ebidy, Gastroenterology Surgical Center, Mansoura University, Mansoura 35516, Egypt
Author contributions: El Nakeeb A designed the research; El Nakeeb A, El Hanafy E, Salah T, Atef E, Hamed H, Sultan AM, Hamdy E, Said M, El Geidie AA, KandilT, El Shobari M and El Ebidy G performed the research; El Nakeeb A and Said M analyzed data; El Nakeeb A and Hamed H wrote the paper.
Institutional review board statement: This study was approved by the institutional review board of Mansoura University.
Informed consent statement: All patients underwent ERCP after a careful explanation of the nature of the disease and possible complications.
Conflict-of-interest statement: There are no potential conflicts of interest relevant to this article.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Ayman El Nakeeb, Associate Professor, Gastroenterology Surgical Center, Mansoura University, El Gomhouria St, Mansoura 35516, Egypt. elnakeebayman@yahoo.com
Telephone: +2-50-2353430 Fax: +2-50-2243220
Received: June 5, 2016
Peer-review started: June 6, 2016
First decision: July 20, 2016
Revised: July 27, 2016
Accepted: August 27, 2016
Article in press: August 29, 2016
Published online: November 16, 2016

Abstract
AIM

To detect risk factors for post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) and investigate the predictors of its severity.

METHODS

This is a prospective cohort study of all patients who underwent ERCP. Pre-ERCP data, intraoperative data, and post-ERCP data were collected.

RESULTS

The study population consisted of 996 patients. Their mean age at presentation was 58.42 (± 14.72) years, and there were 454 male and 442 female patients. Overall, PEP occurred in 102 (10.2%) patients of the study population; eighty (78.4%) cases were of mild to moderate degree, while severe pancreatitis occurred in 22 (21.6%) patients. No hospital mortality was reported for any of PEP patients during the study duration. Age less than 35 years (P = 0.001, OR = 0.035), narrower common bile duct (CBD) diameter (P = 0.0001) and increased number of pancreatic cannulations (P = 0.0001) were independent risk factors for the occurrence of PEP.

CONCLUSION

PEP is the most frequent and devastating complication after ERCP. Age less than 35 years, narrower median CBD diameter and increased number of pancreatic cannulations are independent risk factors for the occurrence of PEP. Patients with these risk factors are candidates for prophylactic and preventive measures against PEP.

Key Words: Pancreatitis, Obstructive jaundice, Endoscopic retrograde cholangiopancreatography

Core tip: Endoscopic retrograde cholangiopancreatography (ERCP) is increasingly used for therapeutic management of various biliary and pancreatic diseases. However, ERCP is not a procedure without morbidities. Post-ERCP pancreatitis (PEP) remains the most devastating and frequent complication after ERCP. Identification of risk factors for PEP helps adopt prophylactic measures in high risk patients and early discharge in low risk patients. Age less than 35 years, narrower median common bile duct diameter and increased number of pancreatic cannulations were identified to be independent risk factors for the occurrence of PEP.



INTRODUCTION

Endoscopic retrograde cholangiopancreatography (ERCP) is increasingly used for therapeutic management of various biliary and pancreatic diseases[1]. However, ERCP is not a procedure without morbidities[2]. Post-ERCP pancreatitis (PEP) remains the most common and serious complication after ERCP[3]. The reported incidence of PEP is around 5%[4,5]. This rate may increase up to 20%-40% in high risk patients. Although the majority of PEP cases are of mild degree, it can be severe and life threatening in a substantial proportion of cases[6].

Identification of risk factors for PEP helps adopt prophylactic measures in high risk patients and early discharge in low risk patients[1,7,8]. Being convinced with a number of patient-related risk factors, some gastroenterologists and surgeons prefer adoption of alternative management strategies for ERCP whenever possible in high risk patients. Similarly, some endoscopists try to avoid procedure-related risk factors to increases the safety of the procedure. All these factors make identification of risk factors for PEP be of paramount importance for the practice of ERCP.

Many patient and procedure related factors have been suggested to be associated with increased likelihood of PEP[8]. The trigger mechanism and pathogenesis for PEP remain unclear[9]. The aim of this study was to detect risk factors for PEP and investigate the predictors of its severity in a tertiary high volume referral surgical center in Middle East in Egypt.

MATERIALS AND METHODS

This is a prospective cohort study of all patients who underwent ERCP between August 2012 and September 2014. Excluded patients were those who presented with obstructed stent, active pancreatitis, previous endoscopic sphinterotomy, biliary complications after liver transplantation, dye allergy, pregnancy, or mental disability.

Patients were admitted 24 h before the procedure. Baseline laboratory assessment of liver functions, blood count and serum amylase level were done prior to ERCP. No pre-ERCP treatment was used to decrease the risk of PEP. In our center, ERCP is performed under general anesthesia with endotracheal intubation in left semi prone position with monitoring of oxygen saturation, heart rate, and blood pressure. The procedure was performed by experienced endoscopists who had performed at least 1500 ERCPs over the last 10 years. Selective bile duct cannulation was carried out in all patients, but pancreatic duct cannulation was performed when necessary. When three or more attempts were needed due to difficulty in cannulation, precut papillotomy was selectively performed. In addition, endoscopic papillotomy for stone extraction using balloon, basket and mechanical lithotripsy, bile duct placement of either plastic or self-expanding metallic stent, as well as brush cytology and dilation, were performed when indicted. Pancreatic duct stenting was not used to minimize PEP in our practice.

ERCP data were recorded in a standardized manner including all potential risk factors for PEP. Patients were hospitalized for 24 h after the procedure and observed for symptoms and signs of post-ERCP complications. Complete blood picture and serum amylase level were determined routinely after 6 h and 24 h.

PEP was defined and classified according to the consensus definition and grading system[10]. PEP was defined as new or worsened abdominal pain together with a serum amylase level at least three times normal at more than 24 h after ERCP and necessitating hospitalization for more than one night. PEP was graded according to the length of hospital stay and the need for intervention. Mild PEP required hospitalization for 2-3 nights, moderate PEP required hospitalization for 4-10 nights, and severe pancreatitis required hospitalization for more than 10 d, or required intervention or was complicated by pseudocyst[10].

Descriptive data are presented as means and standard deviation or medians with range according to the data distribution. Comparison of means was done by χ2 test for categorical data or Student’s t test for continuous data. Difference was considered significant when a P-value was less than 0.05. Independent risk factors for PEP were assessed by multiple logistic regression. Statistical analyses of the data in this study were performed using SPSS software, version 17 (Chicago, IL).

RESULTS

From August 2012 to September 2014, a total of 1296 patients underwent ERCP at Gastrointestinal Surgical Center, Mansoura University, Egypt. The study population consisted of 996 cases after exclusion of those who presented with obstructed stent (n = 66), active pancreatitis (n = 24), previous endoscopic sphinterotomy (n = 110), biliary complications after liver transplantation (n = 36), dye allergy (n = 10), pregnancy (n = 14), or mental disability (n = 10).

Indications for ERCP were malignant obstructive jaundice due to periampullary tumor (n = 460, 46.2%) or hilar cholangiocarcinoma (n = 2, 0.2%), calcular obstructive jaundice (n = 512, 51.4%), benign biliary stricture (n = 10, 1.0%), and post-cholecystectomy biliary leakage (n = 12, 1.2%). The mean age at presentation was 58.42 (± 14.727) years. There were 554 male in comparison to 442 female patients, with a male to female ratio of 1.3:1.

Overall, PEP occurred in 102 (10.2%) patients of the study population. Eighty (78.4%) cases were of mild to moderate degree, while severe pancreatitis occurred in 22 (21.6%) patients. The median length of hospital stay in patients with pancreatitis was 3 d (range, 2-15 d). No hospital mortality was reported for any of PEP patients during the study duration. Univariate analysis showed that patient age and narrower CBD diameter are statistically significant patient-related risk factors associated with occurrence and severity of PEP, while increased number of cannulation attempts and pancreatic cannulation more than three times were significant procedure-related risk factors associated with occurrence and severity of PEP. Indication for ERCP was not significantly associated with occurrence of pancreatitis (P = 0.4), but it was significantly associated with the severity of PEP (P = 0.009) (Tables 1 and 2).

Table 1 Risk factors for pancreatitis after endoscopic retrograde cholangiopancreatography n (%).
No pancreatitisPancreatitisP-value
894 (89.9)102 (10.2)
Patient related factors
Median age (yr)60480.0001
Age group
< 3532 (7.2)20 (39.2)0.0001
> 35415 (92.8)31 (60.8)
Sex
Male510 (57)44 (43.1)0.05
Female384 (43)58 (56.9)
Median serum bilirubin (mg%)10.612.50.76
< 2124 (88.6)16 (11.4)
> 2770 (90)86 (10)0.72
Median CBD diameter (mm)16100.0001
< 1070 (7.8)58 (56.9)
> 10824 (92.2)44 (43.1)0.0001
Indication for ERCP
Malignant402 (45)40 (39.2)0.43
Benign492 (55)62 (60.8)
Type of papilla
Normal540 (60.4)56 (54.9)0.01
Atrophic18 (2)8 (7.8)
Pregnant68 (7.6)2 (2)
Tumour64 (7.2)4 (3.9)
Redundant66(7.4)12 (11.8)
Juxtadivericular68 (7.6)16 (15.7)
Small60 (6.6)2 (2)
Long10 (1.1)2 (2)
Procedure related factors
Number of cannulation attempts
< 5660 (73.9)58 (56.9)0.01
≥ 6234 (26.1)44 (43.1)
Number of pancreatic cannulations020.0001
< 3 times864 (96.6)60 (58.8)
> 3 times28 (3.4)42 (41.2)0.0001
Method of cannulation
Conventional640 (89.4)76 (10.6)0.7
Precut252 (90.6)26 (9.4)
Biliary sphincter balloon dilatation
No654 (73.2)86 (84.3)0.08
Yes240 (26.8)16 (15.7)
Table 2 Predictors of severity of pancreatitis after endoscopic retrograde cholangiopancreatography n (%).
Mild to moderate pancreatitis (80)Severe pancreatitis (22)P-value
Patient related factors
Median age (yr)52300.0001
Age
< 3526 (32.5)14 (63.6)0.0001
> 3554 (67.5)8 (36.4)
Sex
Male38 (47.5)6 (27.3)0.08
Female42 (52.5)16 (72.7)
Median serum bilirubin (mg%)14.19.90.3
< 28 (50)8 (50)
> 272 (85.7)14 (14.3)0.07
Median CBD diameter (mm)1090.0001
< 1042 (52.5)16 (72.7%)
> 1038 (47.5)6 (27.3%)0.0001
Indication for ERCP
Malignant39 (97.5)1 (2.5)0.009
Benign41 (66.1)21 (33.9)
Type of papilla
Normal39170.06
Atrophic62
Pregnant02
Tumour40
Redundant93
Juxtadivericular151
Small20
Long20
Procedure related factors
No. of cannulation attempts
< 546 (57.5)12 (54.5)0.03
≥ 634 (27.5)10 (45.5)
Median number of pancreatic cannulations240.0001
< 3 times58 (72.5)2 (9.1)0.0001
> 3 times22 (52.4)20 (90.9)
Method of cannulation
Conventional58 (72.5)18 (81.8)0.07
Precut22 (52.4)4 (18.2)
Biliary sphincter balloon dilatation
No70 (87.5)16 (72.7)0.1
Yes10 (12.5)6 (27.3)

Multivariate analysis after binary logistic regression analysis revealed that patient age less than 35 years (P = 0.001, OR = 0.035), narrower median CBD diameter (P = 0.0001) and increased number of pancreatic cannulations (P = 0.0001) were independent risk factors for the occurrence of PEP (Table 3).

Table 3 Multivariate logistic regression for analysis of pancreatitis after endoscopic retrograde cholangiopancreatography.
VariableP-valueOdds ratio95%CI for EXP(B)
LowerUpper
Age group0.0010.0350.0050.259
Age0.5191.0120.9761.050
Sex0.3620.1430.0750.270
CBD diameter below 10 mm0.6090.7260.2122.481
CBD diameter0.0000.6120.4950.757
Difficult cannulation0.2070.4760.1501.506
No. of pancreatic cannulations below 30.1170.2190.0331.460
No. of pancreatic cannulations0.0005.2582.66510.370
Papilla0.964
DISCUSSION

PEP is the most common and serious complication after ERCP[8]. PEP is associated with higher morbidity and mortality beside its effect in increasing the consumption of hospital resources[11]. Identification of clinical and procedural correlates for PEP is of crucial importance in the practice of ERCP. It affects the medical decision regarding patient choice, adoption of pharmacological prophylactic measures, avoidance of procedural risk factors, and determination of the time of discharge after the procedure[1,7,8]. Risk factors for PEP have been a matter of controversy and the pathogenesis of PEP is not fully understood yet[9,11]. This study reports risk factors for PEP according to the experience of a tertiary high volume surgical center in Egypt.

Despite advanced accessories and novel techniques in ERCP, complication rate after ERCP remained unchanged over the last decade[7,12]. According to previous reports, the incidence of PEP ranges from 5% to 40%. This great discrepancy in the reported rates can be attributed to heterogeneity of the definition of PEP and its grading system, variability in data collection, inclusion of diagnostic ERCP in the study, and difference in expertise among endoscopists[13]. The incidence of PEP in this cohort was 10.2% with adoption of the consensus definition of PEP[10]. Mild to moderate PEP occurred in 80 (8%) patients, while severe PEP occurred in 22 (2.2%) patients. These ratios are concordant with data reported by previous studies[14-16].

Among different patient related risk factors, younger age and non-dilated extrahepatic biliary radicals were independent risk factors for PEP on multivariate analysis in this study. Also, using a cutoff value of 35 years to divide patients into two groups, the rate of PEP was significantly higher in the younger group by univariate analysis. Younger age has been a subject of controversy regarding its association with PEP[8]. Many studies reported an insignificant relation between patient age and likelihood of PEP[2,17]. However, Freeman et al[18] first reported relatively younger age as a predictor of PEP on multivariate analysis. This finding was confirmed by later studies[5,16,19]. Higher incidence of PEP in younger age was explained by the aging effect on pancreatic exocrine function, smaller common bile duct diameter and the higher incidence of sphincter of Oddi dysfunction in younger age[13,16,18].

Management of CBD stones in case of non-dilated extrahepatic biliary system represents a surgical challenge[20]. Laparoscopic transcholedochal CBD exploration mandates a CBD diameter of at least 6-8 mm[21-23]. According to many studies including this one, normal caliber CBD is associated with increased difficulty of the ERCP procedure[24-26]. However, most of recent studies reported absence of association between narrower CBD diameter and PEP[13]. Laparoscopic management for surgically fit patients with concomitant gall bladder and CBD stones in case of non-dilated CBD through transcystic CBD exploration or laparoendoscopic Rendez-vous is better to avoid or minimize the risk of PEP[21]. In case of isolated choledocholithiasis or in patients who are unfit for surgery, prophylactic measures against PEP should be adopted.

In this cohort, difficult cannulation, denoted by frequent cannulation attempts and pancreatic cannulation more than three times, was associated with a higher risk of PEP. The effect of pancreatic duct injection with contrast dye on PEP could not be evaluated because we did not use the conventional contrast cannulation method. The effect of precut sphincterotomy on PEP is controversial[11]. Some authors advocate that precut sphincterotomy causes papillary oedema which retains pancreatic secretion resulting in PEP[8,24]. On the other hand, some authors indicate that precut sphincterotomy is usually preceded by difficult cannulation through the conventional approach and that the later, not the precut sphincterotomy itself, is responsible for the development of PEP[26]. This is supported by the finding that precut sphinctertomy was not reported as a risk factor for PEP from endoscopists who adopted precut sphincterotomy as a preferred technique from the start not just a salvage procedure after difficult cannulation through conventional cannulation methods[27]. Early precut leads to more successful cannulation rate without more hazard of morbidity after ERCP[28-33].

Risk factors for PEP have a synergetic effect[8]. Jeurnink et al[1] suggested that development of prognostic models and scoring systems based on various patient and procedure related risk factors will help in defining patients at the highest risk for PEP. According to this cohort, young patients (< 35 years) with narrow CBD (< 10 mm) who had shown evidence of difficult cannulation (high number of cannulation attempts or pancreatic cannulation more than three times) are candidates for prophylactic and preventive measures against PEP[28].

Despite the improvement of techniques of ERCP in recent years and increased experiences, the incidence of PEP has not decreased. Therefore, studies to determine risky patients and predict severity of PEP are very important to give the risk factors prophylactic agents for prevention of PEP[34-37]. Pre-ERCP administration of rectal indometacin reduced the overall occurrence of PEP without increasing risk of bleeding[34]. Some studies reported that the combination of a temporary prophylactic pancreatic plastic stent placement and rectal non-steroidal anti-inflammatory drugs is recommended for preventing PEP in high-risk cases[34-36]. Somatostatin can reduce the incidence of PEP but has not been routinely administrated in most of centers nor recommended by guidelines as a prophylactic measure for PEP[36,37]. Patients at high risk of PEP should be also monitored for at least 24 h to avoid occurrence of PEP after early discharge[1,7].

In conclusion, PEP is the most frequent and devastating complication after ERCP. PEP is associated with higher morbidity and mortality beside its effect in increasing the consumption of hospital resources. Age less than 35 years, narrower median CBD diameter and increased number of pancreatic cannulations are independent risk factors for the occurrence of PEP. Patients with these risk factors are candidates for prophylactic and preventive measures against PEP.

COMMENTS
Background

Endoscopic retrograde cholangiopancreatography (ERCP) is increasingly used for therapeutic management of various biliary and pancreatic diseases. However, ERCP is not a procedure without morbidities. Post-ERCP pancreatitis (PEP) remains the most common and serious complication after ERCP. The reported incidence of PEP is around 5%. This rate may increase up to 20%-40% in high risk patients. Identification of risk factors for PEP helps adopt prophylactic measures in high risk patients and early discharge in low risk patients.

Research frontiers

Many studies have tried to identify the risk factors for pancreatitis after ERCP. Many patient and procedure related factors are suggested to be associated with increased likelihood of PEP. The trigger mechanism and pathogenesis for PEP remain unclear.

Innovations and breakthroughs

ERCP is not a procedure without morbidities. Identification of risk factors for PEP helps adopt prophylactic measures in high risk patients and early discharge in low risk patients.

Applications

The data in this study suggested risk factors for PEP and investigated the predictors of its severity in a tertiary high volume. Furthermore, this study also provided readers with important information regarding the risk factors for PEP.

Terminology

PEP remains the most devastating and frequent complication after ERCP. The reported incidence of PEP is around 5%. This rate may increase up to 20%-40% in high risk patients.

Peer-review

This is an interesting manuscript with a significant number of patients treating an important topic, and the aim of this study was to detect risk factors for PEP and investigate the predictors of its severity in a tertiary high volume referral surgical center in Egypt.

Footnotes

Manuscript source: Unsolicited manuscript

Specialty type: Gastroenterology and hepatology

Country of origin: Egypt

Peer-review report classification

Grade A (Excellent): 0

Grade B (Very good): B, B

Grade C (Good): C, C, C

Grade D (Fair): D

Grade E (Poor): 0

P- Reviewer: Hauser G, Gonzalez-Ojeda A, Ikeuchi N, Malak M, Sferra TJ, Shi H S- Editor: Qi Y L- Editor: Wang TQ E- Editor: Li D

References
1.  Jeurnink SM, Siersema PD, Steyerberg EW, Dees J, Poley JW, Haringsma J, Kuipers EJ. Predictors of complications after endoscopic retrograde cholangiopancreatography: a prognostic model for early discharge. Surg Endosc. 2011;25:2892-2900.  [PubMed]  [DOI]
2.  Cotton PB, Garrow DA, Gallagher J, Romagnuolo J. Risk factors for complications after ERCP: a multivariate analysis of 11,497 procedures over 12 years. Gastrointest Endosc. 2009;70:80-88.  [PubMed]  [DOI]
3.  Yang D, Draganov PV. Indomethacin for post-endoscopic retrograde cholangiopancreatography pancreatitis prophylaxis: is it the magic bullet? World J Gastroenterol. 2012;18:4082-4085.  [PubMed]  [DOI]
4.  Williams EJ, Taylor S, Fairclough P, Hamlyn A, Logan RF, Martin D, Riley SA, Veitch P, Wilkinson ML, Williamson PR. Risk factors for complication following ERCP; results of a large-scale, prospective multicenter study. Endoscopy. 2007;39:793-801.  [PubMed]  [DOI]
5.  Cheng CL, Sherman S, Watkins JL, Barnett J, Freeman M, Geenen J, Ryan M, Parker H, Frakes JT, Fogel EL. Risk factors for post-ERCP pancreatitis: a prospective multicenter study. Am J Gastroenterol. 2006;101:139-147.  [PubMed]  [DOI]
6.  Moon SH, Kim MH. Prophecy about post-endoscopic retrograde cholangiopancreatography pancreatitis: from divination to science. World J Gastroenterol. 2013;19:631-637.  [PubMed]  [DOI]
7.  Katsinelos P, Lazaraki G, Chatzimavroudis G, Gkagkalis S, Vasiliadis I, Papaeuthimiou A, Terzoudis S, Pilpilidis I, Zavos C, Kountouras J. Risk factors for therapeutic ERCP-related complications: an analysis of 2,715 cases performed by a single endoscopist. Ann Gastroenterol. 2014;27:65-72.  [PubMed]  [DOI]
8.  Dumonceau JM, Andriulli A, Deviere J, Mariani A, Rigaux J, Baron TH, Testoni PA. European Society of Gastrointestinal Endoscopy (ESGE) Guideline: prophylaxis of post-ERCP pancreatitis. Endoscopy. 2010;42:503-515.  [PubMed]  [DOI]
9.  Tammaro S, Caruso R, Pallone F, Monteleone G. Post-endoscopic retrograde cholangio-pancreatography pancreatitis: is time for a new preventive approach? World J Gastroenterol. 2012;18:4635-4638.  [PubMed]  [DOI]
10.  Cotton PB, Lehman G, Vennes J, Geenen JE, Russell RC, Meyers WC, Liguory C, Nickl N. Endoscopic sphincterotomy complications and their management: an attempt at consensus. Gastrointest Endosc. 1991;37:383-393.  [PubMed]  [DOI]
11.  Chen JJ, Wang XM, Liu XQ, Li W, Dong M, Suo ZW, Ding P, Li Y. Risk factors for post-ERCP pancreatitis: a systematic review of clinical trials with a large sample size in the past 10 years. Eur J Med Res. 2014;19:26.  [PubMed]  [DOI]
12.  Freeman ML. Complications of endoscopic retrograde cholangiopancreatography: avoidance and management. Gastrointest Endosc Clin N Am. 2012;22:567-586.  [PubMed]  [DOI]
13.  Testoni PA, Mariani A, Giussani A, Vailati C, Masci E, Macarri G, Ghezzo L, Familiari L, Giardullo N, Mutignani M. Risk factors for post-ERCP pancreatitis in high- and low-volume centers and among expert and non-expert operators: a prospective multicenter study. Am J Gastroenterol. 2010;105:1753-1761.  [PubMed]  [DOI]
14.  Perney P, Berthier E, Pageaux GP, Hillaire-Buys D, Roques V, Fabbro-Peray P, Melki M, Hanslik B, Bauret P, Larrey D. Are drugs a risk factor of post-ERCP pancreatitis? Gastrointest Endosc. 2003;58:696-700.  [PubMed]  [DOI]
15.  Andriulli A, Clemente R, Solmi L, Terruzzi V, Suriani R, Sigillito A, Leandro G, Leo P, De Maio G, Perri F. Gabexate or somatostatin administration before ERCP in patients at high risk for post-ERCP pancreatitis: a multicenter, placebo-controlled, randomized clinical trial. Gastrointest Endosc. 2002;56:488-495.  [PubMed]  [DOI]
16.  He QB, Xu T, Wang J, Li YH, Wang L, Zou XP. Risk factors for post-ERCP pancreatitis and hyperamylasemia: A retrospective single-center study. J Dig Dis. 2015;16:471-478.  [PubMed]  [DOI]
17.  Masci E, Mariani A, Curioni S, Testoni PA. Risk factors for pancreatitis following endoscopic retrograde cholangiopancreatography: a meta-analysis. Endoscopy. 2003;35:830-834.  [PubMed]  [DOI]
18.  Freeman ML, Nelson DB, Sherman S, Haber GB, Herman ME, Dorsher PJ, Moore JP, Fennerty MB, Ryan ME, Shaw MJ. Complications of endoscopic biliary sphincterotomy. N Engl J Med. 1996;335:909-918.  [PubMed]  [DOI]
19.  Wang P, Li ZS, Liu F, Ren X, Lu NH, Fan ZN, Huang Q, Zhang X, He LP, Sun WS. Risk factors for ERCP-related complications: a prospective multicenter study. Am J Gastroenterol. 2009;104:31-40.  [PubMed]  [DOI]
20.  Sharma A, Dahiya P, Khullar R, Soni V, Baijal M, Chowbey PK. Management of common bile duct stones in the laparoscopic era. Indian J Surg. 2012;74:264-269.  [PubMed]  [DOI]
21.  El Nakeeb A, El Geidie A, El Hanafy E, Atef E, Askar W, Sultan AM, Hamdy E, El Shobary M, Hamed H, Abdelrafee A. Management and Outcome of Borderline Common Bile Duct with Stones: A Prospective Randomized Study. J Laparoendosc Adv Surg Tech A. 2016;26:161-167.  [PubMed]  [DOI]
22.  Shojaiefard A, Esmaeilzadeh M, Ghafouri A, Mehrabi A. Various techniques for the surgical treatment of common bile duct stones: a meta review. Gastroenterol Res Pract. 2009;2009:840208.  [PubMed]  [DOI]
23.  Lee HM, Min SK, Lee HK. Long-term results of laparoscopic common bile duct exploration by choledochotomy for choledocholithiasis: 15-year experience from a single center. Ann Surg Treat Res. 2014;86:1-6.  [PubMed]  [DOI]
24.  Sherman S, Ruffolo TA, Hawes RH, Lehman GA. Complications of endoscopic sphincterotomy. A prospective series with emphasis on the increased risk associated with sphincter of Oddi dysfunction and nondilated bile ducts. Gastroenterology. 1991;101:1068-1075.  [PubMed]  [DOI]
25.  Kahaleh M, Freeman M. Prevention and management of post-endoscopic retrograde cholangiopancreatography complications. Clin Endosc. 2012;45:305-312.  [PubMed]  [DOI]
26.  Chen YK, Foliente RL, Santoro MJ, Walter MH, Collen MJ. Endoscopic sphincterotomy-induced pancreatitis: increased risk associated with nondilated bile ducts and sphincter of Oddi dysfunction. Am J Gastroenterol. 1994;89:327-333.  [PubMed]  [DOI]
27.  Freeman ML, Guda NM. ERCP cannulation: a review of reported techniques. Gastrointest Endosc. 2005;61:112-125.  [PubMed]  [DOI]
28.  Zhang QS, Han B, Xu JH, Gao P, Shen YC. Needle-knife papillotomy and fistulotomy improved the treatment outcome of patients with difficult biliary cannulation. Surg Endosc. 2016; Epub ahead of print.  [PubMed]  [DOI]
29.  Ayoubi M, Sansoè G, Leone N, Castellino F. Comparison between needle-knife fistulotomy and standard cannulation in ERCP. World J Gastrointest Endosc. 2012;4:398-404.  [PubMed]  [DOI]
30.  Swan MP, Alexander S, Moss A, Williams SJ, Ruppin D, Hope R, Bourke MJ. Needle knife sphincterotomy does not increase the risk of pancreatitis in patients with difficult biliary cannulation. Clin Gastroenterol Hepatol. 2013;11:430-436.e1.  [PubMed]  [DOI]
31.  Jin YJ, Jeong S, Lee DH. Utility of needle-knife fistulotomy as an initial method of biliary cannulation to prevent post-ERCP pancreatitis in a highly selected at-risk group: a single-arm prospective feasibility study. Gastrointest Endosc. 2016;84:808-813.  [PubMed]  [DOI]
32.  Mariani A, Di Leo M, Giardullo N, Giussani A, Marini M, Buffoli F, Cipolletta L, Radaelli F, Ravelli P, Lombardi G. Early precut sphincterotomy for difficult biliary access to reduce post-ERCP pancreatitis: a randomized trial. Endoscopy. 2016;48:530-535.  [PubMed]  [DOI]
33.  Kim SJ, Kang DH, Kim HW, Choi CW, Park SB, Song BJ, Hong YM. Needle-knife fistulotomy vs double-guidewire technique in patients with repetitive unintentional pancreatic cannulations. World J Gastroenterol. 2015;21:5918-5925.  [PubMed]  [DOI]
34.  Luo H, Zhao L, Leung J, Zhang R, Liu Z, Wang X, Wang B, Nie Z, Lei T, Li X. Routine pre-procedural rectal indometacin versus selective post-procedural rectal indometacin to prevent pancreatitis in patients undergoing endoscopic retrograde cholangiopancreatography: a multicentre, single-blinded, randomised controlled trial. Lancet. 2016;387:2293-301.  [PubMed]  [DOI]
35.  Elmunzer BJ, Serrano J, Chak A, Edmundowicz SA, Papachristou GI, Scheiman JM, Singh VK, Varadurajulu S, Vargo JJ, Willingham FF. Rectal indomethacin alone versus indomethacin and prophylactic pancreatic stent placement for preventing pancreatitis after ERCP: study protocol for a randomized controlled trial. Trials. 2016;17:120.  [PubMed]  [DOI]
36.  Yin HK, Wu HE, Li QX, Wang W, Ou WL, Xia HH. Pancreatic Stenting Reduces Post-ERCP Pancreatitis and Biliary Sepsis in High-Risk Patients: A Randomized, Controlled Study. Gastroenterol Res Pract. 2016;2016:9687052.  [PubMed]  [DOI]
37.  Qin X, Lei WS, Xing ZX, Shi F. Prophylactic effect of somatostatin in preventing Post-ERCP pancreatitis: an updated meta-analysis. Saudi J Gastroenterol. 2015;21:372-378.  [PubMed]  [DOI]