Abstract
Background
Pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP).
Aim
To assess the prevalence and factors associated with post-ERCP pancreatitis (PEP) in a Chinese pediatric population.
Methods
Sixty-six children who underwent ERCP between March 2018 and March 2019 at Shanghai Children’s Medical Center were retrospectively recruited for the study. Clinical data, including demographics, indications, comorbidities, and procedural data, were reviewed to identify the prevalence and factors associated with PEP.
Results
Ninety-two ERCPs were performed on 66 pediatric patients aged from 8 months to 14 years. The indications for ERCP were chronic pancreatitis (49, 53.2%), pancreaticobiliary maljunction (19, 20.7%), pancreas divisum (19, 20.7%), and pancreatic pseudocyst (5, 5.4%). All ERCPs were performed for therapeutic purposes. PEP was identified in 19 (20.7%) patients; there were ten mild cases, eight moderate cases, and one severe case. The univariate analysis revealed that a history of chronic pancreatitis was negatively associated with PEP (P = 0.033), and sphincterotomy was positively associated with PEP (P = 0.01). The multivariate analysis showed that sphincterotomy was a risk factor for PEP (P = 0.017, OR 4.17; 95% CI, 1.29, 13.54).
Conclusions
Our data revealed a high prevalence of PEP in a Chinese pediatric population. Chronic pancreatitis was a protective factor, and sphincterotomy was a risk factor for PEP development.
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Introduction
Endoscopic retrograde cholangiopancreatography (ERCP) is an endoscopic technique that combines gastrointestinal endoscopy and fluoroscopy for the diagnosis and treatment of pancreatic and biliary diseases [1]. ERCP has been used routinely in adults for over 50 years [1]. The application of ERCP in children has been increasing in recent years, but it is still used conservatively based on insufficient experience, limited safety and effectiveness data, and limited operator qualification [2, 3]. Although ERCP allows minimally invasive access to the pancreatic and biliary duct, complications after the procedure occur in both adults and children [3, 4]. Post-ERCP pancreatitis (PEP) is recognized as the most common complication with varied prevalence in different studies [4,5,6]. The identification of risk factors for PEP is very important for the development of preventive strategies. For example, studies have shown that prophylactic pancreatic duct (PD) stent placement, the use of statins, and rectal indomethacin administration could decrease the incidence and severity of PEP in high-risk adult patients [7,8,9,10,11].
Recent case series studies reported that the prevalence of PEP ranged from 1.2 to 10.9% in the pediatric population [12,13,14,15,16]. Various factors associated with PEP were identified in pediatric patients [12, 14]. It was reported that therapeutic procedures and the presence of chronic pancreatitis were risk factors for PEP in a study that included 343 ERCPs performed in 224 children [12]. Troendle et al. [14] showed that PD injection and pancreatic sphincterotomy were positively associated with PEP, whereas a history of chronic pancreatitis was negatively associated with PEP. The wide range in prevalence and various risk factors for PEP in pediatric populations may be due to differences in procedural indications and comorbidities between the study populations.
The prevalence and factors associated with PEP in European and North American pediatric patients have been reported in the literature. However, a similar study is currently lacking in the Chinese pediatric population. Here, we conducted a single-center retrospective study to investigate the PEP prevalence and associated factors in pediatric patients in China.
Materials and Methods
Study Cohort
A total of 66 children aged 8 months to 14 years who underwent ERCP between March 2018 and March 2019 at Shanghai Children’s Medical Center were retrospectively recruited for the study. Clinical data, including demographics, indications, comorbidities, and procedural data, were collected and reviewed to identify the PEP prevalence and associated factors. This study was in compliance with the Helsinki Declaration and was approved by the Ethical Review Board of Shanghai Children’s Medical Center. Written informed consent was obtained from the parents or legal guardians of all pediatric patients.
ERCP Procedures
ERCP procedures were performed by an adult gastroenterologist with significant experience specifically with ERCP. (The physician had performed more than 30,000 ERCPs.) A pediatric endoscope (JF-240, Olympus, Tokyo, Japan) was typically used. The outer diameter and channel size of the JF-240 endoscope are 12.6 mm and 3.2 mm, respectively. It allows use of all ERCP accessories essential for a therapeutic procedure in our study patients. Indications for ERCP were dependent on clinical history, physical examination, laboratory tests (liver function, serum amylase, and lipase levels), abdominal ultrasound, computed tomography (CT), magnetic resonance cholangiopancreatography (MRCP), and prior ERCP findings. Patients were hospitalized 2 days before ERCP. The ERCP procedures were performed with the patient in the prone position under general anesthesia, with continuous monitoring of vital functions. Iohexol (300 mg/30 mL) diluted 1:1 with sterile water was used for the cholangiography and pancreatography. Appropriate therapeutic procedures were performed, including endoscopic sphincterotomy (both biliary and pancreatic), pancreatic and biliary duct stenting, stricture dilation, and biliary or pancreatic stone extraction. Patients with pancreatic pseudocysts directly communicating with the main pancreatic duct had pancreatic duct stents placed during the ERCP for drainage of the pancreatic pseudocysts. The management of symptomatic pancreas divisum includes minor papillotomy, pancreatic duct dilatation, and pancreatic duct stent placement. Minor papillotomy was performed in all patients with symptomatic pancreas divisum undergoing their first ERCP procedure. Minor papillotomy was not performed repeatedly in patients who had undergone previous ERCP. Success of the procedure was defined as allowing adequate therapy for the prespecified indication. Serum amylase concentrations were measured by using a VITROS chemistry method (VITROS 250, Johnson & Johnson Ltd., NY, USA) at 24 h after the procedure. The reference range for the amylase level is 30–110 U/L. The patients who met discharge criteria (tolerated oral intake, had no complaints of pain, and had normal blood amylase levels) were discharged. Patients not meeting discharge criteria were admitted for further evaluation.
Diagnosis of PEP
PEP was diagnosed according to the 1991 consensus criteria statement and the revised Atlanta classification for the diagnosis of acute pancreatitis [17, 18]. PEP was defined as new or increased abdominal pain typical of acute pancreatitis and at least a threefold elevation in serum amylase levels 24 h after the procedure, resulting in hospitalization (or prolongation of existing hospitalization) of at least two nights, or evidence of pancreatic inflammation on abdominal imaging [17, 18]. The severity of pancreatitis was classified according to Cotton’s criteria as follows: mild if additional hospitalization for 1–3 days was required; moderate if additional hospitalization for 4–10 days was required; and severe if hospitalization for more than 10 days was needed, as well as in cases of hemorrhagic pancreatitis, phlegmon, or pseudocysts [17]. After the ERCP procedure, increased hospital stays that were caused by medical issues other than PEP were excluded in the severity classification. ERCP procedural data of patients not complicated by pancreatitis were also collected and reviewed to identify factors associated with PEP.
Statistical Analysis
All data were entered into a customized database and then analyzed by R software 3.5.1 (The R Foundation, Vienna, Austria). For patients who underwent more than one ERCP, each individual ERCP procedure was assumed to be a statistically independent observation. Quantitative data were summarized as the mean ± standard deviation (SD) or number with percentage, where appropriate. The Chi-square test was used to evaluate the differences in general characteristics between patients with PEP and those without PEP. Multivariate binary logistic regression analysis was conducted. Sex and PD stent placement were analyzed in the final model. Chronic pancreatitis was not included in the multivariate analysis due to a high correlation with pancreatic pseudocysts, which could have caused collinearity problems. Statistical significance was considered when the two-sided P value was < 0.05.
Results
Baseline Characteristics
As shown in Table 1, a total of 92 ERCPs were performed in 66 pediatric patients at our center during the study period. The mean age of the children was 7.1 ± 4.3 years (ranging from 8 months to 14 years). Thirty patients (45.4%) had undergone previous ERCP. CT or MRCP was performed on all patients to confirm the indications prior to ERCP, and the indications for ERCP were chronic pancreatitis with repeated attacks of pancreatitis (49, 53.2%), pancreaticobiliary maljunction complicated with recurrent retrograde cholangitis or pancreatitis (19, 20.7%), pancreas divisum concomitant with recurrent pancreatitis (19, 20.7%), and pancreatic pseudocyst with a cyst larger than 6 cm that did not shrink after 1 month of conservative medical treatment (5, 5.4%). Patients with chronic pancreatitis undergoing ERCP had pancreatic ductal dilatation and/or diffuse calcification that was confirmed by CT, MRCP, or prior ERCP. All ERCP procedures were performed for therapeutic purposes, and the ERCP success rate was 100%. Sphincterotomy was performed in 39 cases, including pancreatic sphincterotomy (20, 21.7%), minor papillotomy (8, 8.7%), and biliary sphincterotomy (11, 12.0%). PD stricture dilation was performed in 64 (69.6%) cases, and common bile duct (CBD) stricture dilation was performed in 15 (16.3) cases. PD stents and CBD stents were placed in 54 (58.7%) and ten (10.9%) cases, respectively. Endoscopic nasopancreatic drainage and endoscopic nasobiliary drainage were performed in 14 (15.2%) and three (2.2%) patients, respectively. Stone extraction was performed by balloon manipulation and basket catheter in 13 (14.1%) and 12 (13.0%) patients, respectively. The number of cannulation attempts to successful cannulation in most ERCPs (73, 79.3%) was 1 time with duration less than 2 min. Pancreatogram and cholangiogram were undertaken in 86 (93.5%) and 20 (21.7%) patients, and the majority of patients (79, 85.9%) received a contrast agent dose of less than 5 mL.
Prevalence and Severity of PEP
PEP was identified in 19 (20.7%) of the 92 ERCPs; there were ten mild cases, eight moderate cases, and one severe case of PEP (Table 2). The mean age of the patients who developed PEP was 7.7 ± 3.7 (range 3–14 years). As shown in Table 3, the indications were chronic pancreatitis (7, 36.8%), pancreaticobiliary maljunction (6, 31.6%), pancreas divisum (3, 15.8%), and pancreatic pseudocyst (3, 15.8%). Ten mild cases had their discharges delayed for 2–3 nights, seven moderate cases had their discharges delayed for 4–7 nights, and the severe case had their discharges delayed for 13 nights. The mean serum amylase level 24 h after the procedure among the patients who developed PEP was 744.5 ± 538.4 U/L (range 312–2400 U/L).
Risk Factors for PEP
The results of the univariate analysis of preprocedural factors showed that there were no significant differences in age, sex, or previous ERCP between children with PEP and those without PEP (Table 4). We found that a history of chronic pancreatitis was negatively associated with PEP (P = 0.033). The serum bilirubin level of all patients was in the normal range (data not shown). The univariate analysis of procedural characteristics revealed that patients undergoing sphincterotomy were at a high risk of developing PEP (P = 0.01). The number of cases with prior ERCP who underwent sphincterotomy during an index ERCP was 17, and six cases developed PEP. Prior ERCP has little impact on the incidence of PEP in patients who underwent sphincterotomy (6/17 vs 7/21, P = 0.986). There were no significant differences in endoscopic nasopancreatic drainage, endoscopic nasobiliary drainage, biliary stent placement, doses of contrast agent, or cannulation attempts and duration to successful cannulation between patients with PEP and those without PEP (Tables 4 and 5). Multivariate analysis showed that sphincterotomy was a predictor of PEP in our study cohort (P = 0.017, OR 4.17; 95% CI, 1.29, 13.54, Table 6).
Discussion
In this study, we retrospectively reviewed a total of 92 ERCPs performed on pediatric patients treated at Shanghai Children’s Medical Center, China. The prevalence of PEP was 20.7%, which was higher than that reported from previous studies in both children and adults [5, 12,13,14,15,16]. An early study including 343 ERCPs performed in 224 children reported an overall PEP incidence of 5.0%, including both patients with and without chronic pancreatitis [12]. A PEP rate of 7.4% was reported from a study that included 54 ERCPs performed on 31 children [8]. Troendle et al. [14] identified a PEP prevalence of 10.9% in 432 ERCPs performed on 313 pediatric patients. A recent study that included 856 ERCPs in 626 pediatric patients [16] reported a low incidence of PEP (1.2%). Two major reasons may account for the high incidence of PEP identified in our study population: patient selection and procedural purpose. First, the majority of patients in our study suffered from pancreatic diseases, such as pancreatic pseudocysts and chronic pancreatitis. Li et al. [19] reported a similar PEP rate (17/110, 15.5%) in children and adolescents with chronic pancreatitis. The main indications for ERCP in several previous studies reporting a low PEP rate in pediatric patients were biliary diseases, including choledocholithiasis, cholangitis, or biliary stricture [12, 14]. It has been reported that pediatric patients with biliary diseases have a low risk of PEP development [14]. Nevertheless, previous large studies in pediatric pancreatitis patients reported low rates of PEP [20, 21]. It has been reported that PEP occurred in only seven of 231 ERCPs (7/231, 3.0%), performed in 167 children; the most common indication was chronic or recurrent pancreatitis (106/167, 63.4%) [20]. Agarwal et al. [21] showed that procedure-related adverse events were seen in eight (8/172, 4.7%) patients with pancreatic diseases undergoing ERCP. Second, all ERCPs from our study were therapeutic interventions, such as PD stricture dilation, PD stone extraction, and sphincterotomy. It has been previously shown that pediatric patients undergoing ERCP for diagnosis only were less likely to develop PEP [12]. However, a previous study including 294 endoscopic sphincterotomies among 198 pediatric patients reported that PEP occurred in 17 (5.7%) procedures [22]. In addition, Green et al. [23] reported that no instances of PEP were observed in 23 therapeutic procedures, including sphincterotomy, stent placement, stone removal, and dilation. Thus, future studies enrolling a large pediatric cohort are needed to further explore the roles of the indication and procedural purpose in PEP development.
Both preprocedural and procedural factors have been associated with the incidence of PEP [5]. Preprocedural factors include age, sex, serum bilirubin level, undergoing prior ERCP, and procedural indications, whereas others, such as PD stent placement, pancreatic sphincterotomy, and precut sphincterotomy, are related to the procedure [5]. We showed that young age, female sex, and prior ERCP were not related to the development of PEP in our study cohort. The role of chronic pancreatitis in PEP occurrence is controversial in the literature [24, 25]. Some studies have shown that patients with chronic pancreatitis have a protective effect, related to pancreatic atrophy and decreased exocrine function that was associated with a reduced incidence of PEP [24]. Troendle et al. [14] showed that a history of chronic pancreatitis was negatively associated with PEP in children. In contrast, other studies reported that the incidence of PEP was increased in both adults and pediatric patients with chronic pancreatitis [12, 25]. Here, we showed that chronic pancreatitis was negatively associated with PEP development in our pediatric patients. For other preprocedural factors, the serum bilirubin level of all patients was in the normal range, and suspected sphincter of Oddi dysfunction (SOD) was not observed. In addition, evaluation of the association of pancreatic pseudocysts with PEP development was limited by the fact that only five such patients were included in this series.
For procedural factors, PD stent placement is considered a protective factor that has been associated with reduced PEP incidence in adults [26]. However, it has been reported that PD stent placement was associated with a significantly increased rate of PEP in pediatric patients undergoing PD injection compared with those who had no attempt at stent placement [14]. Additionally, a previous study showed that PD stent placement increased the likelihood of developing PEP in children with chronic pancreatitis [12]. Our data showed that the rate of PEP was similar for children with PD stent placement, children without PD stent placement, and patients undergoing endoscopic nasopancreatic or nasobiliary drainage. The univariate analysis showed that sphincterotomy was a risk factor for the development of PEP, which was consistent with previous studies in both adults and children [5, 14]. Although other factors, such as balloon manipulation and PD injection, have been identified as risk factors for PEP in children [12, 14], they were not related to PEP development in our study population. A previous study showed that pancreatograms were a risk factor for PEP [27]. However, our data indicated that pancreatograms were not related to the incidence of PEP. Furthermore, endoscopist experience has been linked to procedural success and overall adverse event rates of ERCP [24, 28]. Endoscopist experience was not a factor for PEP development in our cohort, as all procedures were performed by the same experienced adult gastroenterologist who had performed more than 30,000 ERCPs. The number of cannulation attempts to successful cannulation in most ERCPs (73, 79.3%) was 1 time with duration less than 2 min. There was no statistical difference in cannulation attempts and duration to successful cannulation between patients with PEP and those without PEP.
There are several limitations in the present study. First, this was a single-center, pilot, retrospective study with a limited number of ERCP cases. Second, the majority of patients undergoing ERCPs in our study suffered from pancreatic diseases, limiting the ability of this study to evaluate the association of biliary diseases with PEP. Third, all ERCPs were performed for therapeutic purposes, and the association of diagnostic procedures with PEP development remains undetermined.
In summary, the prevalence of PEP was 20.7% in our studied Chinese pediatric population. Chronic pancreatitis was negatively associated with PEP, and sphincterotomy was a risk factor for PEP. Given the increasing applications of ERCP in children, more studies are needed to further investigate the safety and effectiveness of ERCP in pediatric patients.
Abbreviations
- CBD:
-
Common bile duct
- ERCP:
-
Endoscopic retrograde cholangiopancreatography
- PD:
-
Pancreatic duct
- PEP:
-
Post-ERCP pancreatitis
- SD:
-
Standard deviation
- SOD:
-
Sphincter of Oddi dysfunction
References
Cotton PB. Fifty years of ERCP: a personal review. Gastrointest Endosc. 2018;88:393–396.
Troendle DM, Barth BA. Pediatric Considerations in Endoscopic Retrograde Cholangiopancreatography. Gastrointest Endosc Clin N Am. 2016;26:119–136.
Muftah M, Shah R, Fritzen C, et al. Endoscopic Retrograde Cholangiopancreatography in Pediatric Populations. Curr Treat Options Gastroenterol. 2019;. https://doi.org/10.1007/s11938-019-00225-6.
Manoharan D, Srivastava DN, Gupta AK, et al. Complications of endoscopic retrograde cholangiopancreatography: an imaging review. Abdom Radiol (NY). 2019;. https://doi.org/10.1007/s00261-019-01953-0.
Anderson MA, Fisher L, Jain R, et al. Complications of ERCP. Gastrointest Endosc. 2012;75:467–473.
Elmunzer BJ. Reducing the risk of post-endoscopic retrograde cholangiopancreatography pancreatitis. Dig Endosc. 2017;29:749–757.
Mazaki T, Masuda H, Takayama T. Prophylactic pancreatic stent placement and post-ERCP pancreatitis: a systematic review and meta-analysis. Endoscopy. 2010;42:842–853.
Elmunzer BJ, Scheiman JM, Lehman GA, et al. A randomized trial of rectal indomethacin to prevent post-ERCP pancreatitis. N Engl J Med. 2012;366:1414–1422.
Sotoudehmanesh R, Eloubeidi MA, Asgari AA, et al. A randomized trial of rectal indomethacin and sublingual nitrates to prevent post-ERCP pancreatitis. Am J Gastroenterol. 2014;109:903–909.
Mahamid M, Watad A, Bragazzi NL, et al. Chronic Use of Statins and Their Effect on Prevention of Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis. Front Pharmacol. 2018;9:704.
Mine T, Morizane T, Kawaguchi Y, et al. Clinical practice guideline for post-ERCP pancreatitis. J Gastroenterol. 2017;52:1013–1022.
Iqbal CW, Baron TH, Moir CR, et al. Post-ERCP pancreatitis in pediatric patients. J Pediatr Gastroenterol Nutr. 2009;49:430–434.
Cheng CL, Fogel EL, Sherman S, et al. Diagnostic and therapeutic endoscopic retrograde cholangiopancreatography in children: a large series report. J Pediatr Gastroenterol Nutr. 2005;41:445–453.
Troendle DM, Abraham O, Huang R, et al. Factors associated with post-ERCP pancreatitis and the effect of pancreatic duct stenting in a pediatric population. Gastrointest Endosc. 2015;81:1408–1416.
Felux J, Sturm E, Busch A, et al. ERCP in infants, children and adolescents is feasible and safe: results from a tertiary care center. United European Gastroenterol J. 2017;5:1024–1029.
Keil R, Drabek J, Lochmannova J, et al. ERCP in infants, children, and adolescents-Different roles of the methods in different age groups. PLoS ONE. 2019;14:e0210805.
Cotton PB, Lehman G, Vennes J, et al. Endoscopic sphincterotomy complications and their management: an attempt at consensus. Gastrointest Endosc. 1991;37:383–393.
Banks PA, Bollen TL, Dervenis C, et al. Classification of acute pancreatitis–2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2013;62:102–111.
Li ZS, Wang W, Liao Z, et al. A long-term follow-up study on endoscopic management of children and adolescents with chronic pancreatitis. Am J Gastroenterol. 2010;105:1884–1892.
Otto AK, Neal MD, Slivka AN, et al. An appraisal of endoscopic retrograde cholangiopancreatography (ERCP) for pancreaticobiliary disease in children: our institutional experience in 231 cases. Surg Endosc. 2011;25:2536–2540.
Agarwal J, Nageshwar Reddy D, Talukdar R, et al. ERCP in the management of pancreatic diseases in children. Gastrointest Endosc. 2014;79:271–278.
Cho JM, Jeong IS, Kim HJ, et al. Early adverse events and long-term outcomes of endoscopic sphincterotomy in a pediatric population: a single-center experience. Endoscopy. 2017;49:438–446.
Green JA, Scheeres DE, Conrad HA, et al. Pediatric ERCP in a multidisciplinary community setting: experience with a fellowship-trained general surgeon. Surg Endosc. 2007;21:2187–2192.
Zhao ZH, Hu LH, Ren HB, et al. Incidence and risk factors for post-ERCP pancreatitis in chronic pancreatitis. Gastrointest Endosc. 2017;86(519):524.
Phillip V, Schwab M, Haf D, et al. Identification of risk factors for post-endoscopic retrograde cholangiopancreatography pancreatitis in a high volume center. PLoS ONE. 2017;12:e0177874.
Choudhary A, Bechtold ML, Arif M, et al. Pancreatic stents for prophylaxis against post-ERCP pancreatitis: a meta-analysis and systematic review. Gastrointest Endosc. 2011;73:275–282.
Wang J, Shen Y, Zhong Z, et al. Risk Factors for Post-Endoscopic Retrograde Cholangiopancreatography (ERCP) Pancreatitis and the Effect of Octreotide Combined with Nonsteroidal Anti-Inflammatory Drugs on Preventing Its Occurrence. Med Sci Monit. 2018;24:8964–8969.
Testoni PA, Mariani A, Giussani A, et al. 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.
Funding
This work was supported by grants from the Shanghai Municipal Health Commission of China (Grant Number 2018LP018, ZY (2018-2020)-FWTX-1105). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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BG and ZD designed the study. ZD drafted the manuscript. JZ, CL, LJ, JJ, XL, and LH acquired, analyzed, and interpreted the data. BG and ZD edited the manuscript. All authors agreed to be accountable for all aspects of the work.
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Written informed consent was obtained from the parents of the patients for the publication of this study. This study was approved by the Regional Ethical Review Board in Shanghai Children’s Medical Center.
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Deng, Z., Zeng, J., Lv, C. et al. Prevalence and Factors Associated with Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis in Children. Dig Dis Sci 66, 224–230 (2021). https://doi.org/10.1007/s10620-020-06179-5
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DOI: https://doi.org/10.1007/s10620-020-06179-5