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Indications, success, and adverse event rates of pediatric endoscopic retrograde cholangiopancreatography (ERCP): a systematic review and meta-analysis

BMC Pediatrics volume 23, Article number: 596 (2023) Cite this article

Abstract

Background

To improve knowledge on endoscopic retrograde cholangiopancreatography (ERCP) in children, we aimed to study the proportion of indications, success rate and complication of ERCP.

Methods

We performed a systematic search of all articles published up to December 2022 in the following databases: Cochrane Library, PubMed (MEDLINE) and Scopus. The meta-analysis was performed using a random-effects model. Heterogeneity was determined by the I2 statistics and the Cochrane Q test. The included data were analyzed to identify the proportion of indications, success rate and complications of ERCP in children.

Results

Based on data from 52 studies with a total of 5624 participants, the most common indications for ERCP in children were biliary [48% (95% CI: 0.40 - 0.57; I2 = 98.17%, P < 0.001)] and both biliary and pancreatic [41% (95% CI: 0.33 - 0.49; I2 = 98.27%, P < 0.001)]. The success rate of ERCP was 95% (95% CI: 0.94 - 0.96; I2 = 82.53%, P < 0.001) with the overall complication rate of 7% (95% CI: 0.05 - 0.09; I2 = 82.06%, P < 0.001). The pooled estimate for the incidence of post ERCP pancreatitis was 4% (95% CI: 0.03 - 0.06; I2 = 85.46%, P < 0.001) and the bleeding was 0% (95% CI: 0.0 - 0.0; I2 = 28.21%, P = 0.03).

Conclusions

ERCP appears to be performed safely in children with a similar success rate as in the adult population.

Peer Review reports

Introduction

Advanced endoscopy, traditionally associated with endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS), continues to evolve as new technology and techniques become available [1, 2]. Advanced endoscopists now have a variety of capabilities, including ERCP, balloon enteroscopy, Capsule Endoscopy, EUS and transabdominal ultrasonography (TUS) and deep small bowel enteroscopy [3]. Pediatric indications differ from adults for ERCP while it is comparable in adolescents such as choledocholithiasis, liver-transplantation related disorders, and malignancy. In contrast, the main indication for ERCP in newborns was diagnostic workup of neonatal cholestasis and suspected pancreaticobiliary maljunction [4, 5]. Considering the rise in the incidence of ERCP in children, an increased risk of complications was also reported in this sub-population [6]. A few authors have expressed their opinion that ERCP could be successfully carried out in children with a similar success rate as observed in adults provided, they are performed by an experienced endoscopist in children, but the evidence is inadequate [7,8,9]. Considering the dearth of data, a systematic in-depth review and analysis of published literature is essential. We focus the discussion on advanced endoscopic methods that have already been developed and are more widely accepted in practice, but it is worth noting that there is an explosion of new endoscopic methods that continue to expand the frontiers of endoscopic treatment.

Method

Search strategy

The study protocol was developed complying the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) checklist. An independent systematic search was implemented in the Cochrane Library, PubMed (MEDLINE), Scopus and Web of Science until April 2023 by two authors (M.H.S. and S.F). The combination of following keywords and Medical Subject Heading (MeSH) terms were used in the search strategies: [“Cholangiopancreatography, Endoscopic Retrograde” OR Endoscopic Retrograde Cholangiopancreatography OR ERCP] AND [indication OR outcome OR outcomes OR success rate OR efficacy OR patient safety OR complications OR] AND [Child OR Adolescent OR Pediatrics OR Pediatric* OR youth* OR teen* OR infant]. We also hand searched the bibliographies of retrieved reviews to find potentially relevant original articles. No language or time limits were imposed in the literature search.

Eligibility criteria

After the elimination of duplicate records, titles and abstracts of identified papers were screened and studies meeting the following criteria were included: (1) the articles were case series, prospective/retrospective cohort studies, case-control studies, or randomized) (2) the studies enrolled pediatric/children/adolescents (aged < 18 years); and (3) the articles reported indication, success rate or complication of ERCP. Duplicate data, studies with unclear information, studies involving animals, reviews and studies whose corresponding author did not offer any feedback after several emails were excluded.

Data extraction

A detailed full-text review was independently performed by two authors (E.Sh. and AH.H.) and the following data were abstracted using standardized pre-piloted forms: reference (first author's name and year of publication), study location, sample size, type of study, participants' characteristics (gender, age), indication, success rate and complication of procedure.

Data synthesis

The statistical analysis was conducted using STATA version 11.0 (Stata Corp, College Station, TX, USA). The pooled estimates for the indications, success rate and complications of ERCP were expressed as proportions with 95% confidence intervals (95% CI) using the random effects model, and presented visually as the Forest plot [10]. Heterogeneity was examined using the I-squared (I2) statistic and the Cochrane Q test in which the heterogeneity was considered significant if the I2 value was ≥ 50%. The significance level for heterogeneity was defined with a significance level of P ≤ 0.10 for Cochran Q. We assessed the presence of publication bias using the Funnel plot and the Egger’s test [11].

Results

Study selection

Figure 1 displays the flow diagram of the study selection process. A total of 5257 articles were identified from the screening process. After the removal of duplicate records, 4467 articles remained and finally 176 articles were retained for full-text review of which 52 articles [5, 7, 9, 12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60] were included in this study.

Fig. 1
figure 1

Flow chart of study selection process

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Study characteristics

The key characteristics of the included studies are summarized in Table 1. All except two [46, 50] had retrospective study design. In general, the included studies were published between 1993 and 2022, and were conducted in the United States of America [14, 18, 20, 21, 23,24,25, 29, 30, 33, 36, 40, 42, 44, 45, 48,49,50,51, 53, 57], China [17, 28, 34, 54, 56, 58,59,60], India [12, 16, 37], Netherlands [52], Germany, [5, 22, 32] Pakistan [46], Turkey [19, 55], Czech Republic [27], Italy [9, 35, 41], Canada [7, 38], Japan [43, 47], Korea [15], Bangladesh [39], Bulgaria [13], France [31], and Saudi Arabia [26]. The number of patients enrolled in each study ranged from 5 to 857 and the mean age (year) range of studies' participants varied between 53 days to 16.2 years. Eight studies [9, 12, 25, 28, 35, 40, 54, 59]reported exclusively on pancreatic ERCPs and three studies [27, 32, 57] on biliary ERCPs.

Table 1 Included study characteristics by population
Full size table

Meta-analysis

Based on the data from 52 studies with a total of 5624 participants, the most common indications for ERCP in pediatric were biliary [48% (95% CI: 0.40 - 0.57; I2 = 98.17%, P < 0.001)] in 3653 patients (Fig. 2) and both biliary and pancreatic [41% (95% CI: 0.33 - 0.49; I2 = 98.27%, P < 0.001)] in 2018 patients (Fig. 3). The success rate of the procedure as 95% (95% CI: 0.94 - 0.96; I2 = 82.53%, P < 0.001) (Fig. 4) with the overall complication rate of 7% (95% CI: 0.05 - 0.09; I2 = 82.06%, P < 0.001) (Fig. 5). To clarify the details of most common complication of ERCP and the source of heterogeneity, we carried out a subgroup analysis based on the Post ERCP pancreatitis and bleeding. Complication of ERCP (pancreatitis and biliary) was observed as a possible source of heterogeneity on the overall effect size. Post ERCP pancreatitis was reported 4% (95% CI: 0.03 - 0.06; I2 = 85.46%, P < 0.001) in 350 and bleeding was 0% (95% CI: 0.0 - 0.0; I2 = 28.21%, P = 0.03) as observed only in 40 patients out of the total 5900 (Fig. 6). Considering the significant heterogeneity to identify the source, further subgroup analyses were performed by age group and the ERCP center. On the basis of subgroup analyses, none of the variables examined represented a source of heterogeneity, but the subgroup analysis showed the overall complication of ERCP was greater 10% [95% CI: 0.06 - 0.14] in children between age 2-10 years compared with the other age groups [ for < 2 years: 8% (95% CI: 0.02 - 0.19) and for > 10 years: 6% (95% CI: 0.05 - 0.09)]. These results were similar for success rate, in that the success rate for the children between age 2-10 years was %97 (95% CI: 0.93 - 1.0) and was higher compared to other age groups [for < 2 years: 0.93 (95% CI: 0.89 - 0.96) and for > 10 years: %95 (95% CI: 0.92 - 0.96)].

Fig. 2
figure 2

This figure shows the pooled estimate of the proportion ERCP indication (biliary) in pediatric

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Fig. 3
figure 3

This figure shows the pooled estimate of the proportion ERCP indication (pancreatic) in pediatric

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Fig. 4
figure 4

This figure shows the pooled estimate of the proportion of overall success rate of ERCP in pediatric

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Fig. 5
figure 5

This figure shows the pooled estimate of the proportion of overall complication rate of ERCP in pediatric

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Fig. 6
figure 6

This figure shows the pooled estimate of the proportion of A) Post ERCP pancreatitis and B) Post ERCP bleeding in children

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Publication bias

The evaluation of publication bias by visual inspection of the funnel plot and Egger’s test demonstrated some evidence for publication bias in the meta-analysis of biliary indication of ERCP (P = 0.040). However, the results of the meta trim and fill analysis did not reveal any presence of additional studies other than those included in this meta-analysis. Egger’s linear regression test for elevated pancreatic indication (P = 0.284), success rate (P = 0.355), and complication rate (P = 0.500) did not reveal presence of any publication bias (Fig. 7).

Fig. 7
figure 7

Funnel plots of primary and secondary outcomes using random-effects model a) biliary indication, b pancreatic indication, c success rate and d) complication rate

Full size image

Discussion

The present meta-analysis was carried out for evaluating the indications, success rate, and complications of ERCP in children. We observed through a total of 5624 participants in 52 studies, the most common indications were biliary and almost 95% of the procedure was successful with a very satisfactory rate of overall complication (7%). Our results are very assuring considering the fact that ERCP provides an opportunity for visualization of the biliary tract in infants and can replace the non-invasive imaging by magnetic resonance cholangiopancreatography (MRCP) [61]. Our study had a much higher success rate compared to the results carried out in adults where the pooled estimates for single-balloon enteroscopy (SBE-) assisted ERCP in biliary interventions revealed with a success rate of 75.8% [62]. Similarly, results from Sun et al. [63], revealed a success rate of 74% and the incidence of side effects as 8% compared to the present study where the success rate and complication rate of 95% and 7%, respectively. Additionally, the previous study was also limited in not revealing the indications for ERCP, unlike the present study, instead, there were interesting results regarding stent placement as the most common method (75%) and the usage proportion of sphincterotomy (ST), stone extraction/removal and bougienage/balloon dilation. Usatin et al [64] evaluated the same outcome measures in a meta-analysis of 32 studies (2612 study participants) where biliary indications contributed to 54% of the cases with an overall complication rate of 6%. The authors have also observed a similar rate of pancreatitis (3%) and bleeding (0.6%) as shown in the present study. Although some studies have observed injection of contrast medium in the pancreatic duct and pancreatic sphincterotomy as the risk factors for post-ERCP pancreatitis [8], we could not evaluate it in the present study owing to data constraints. Additionally, none of the studies have evaluated mortality following ERCP despite 0.11% observed in the adult population [6]. Although the overall complication rates following ERCP were low, it is still significant particularly in terms of the morbidity due to post-ERCP pancreatitis. Due to the limited number of pediatric cases requiring ERCP, in many centers, ERCP is carried out by adult gastroenterologists with a reasonable success rate and low complication rates [24]. It is still debatable whether a pediatric gastroenterologist should only perform the ERCP in children or a trained adult gastroenterologist in the pediatric procedures can be involved in doing so particularly with the limited data in the literature. Post-ERCP pancreatitis has been observed to be 4% in the present study like the rates observed in adult populations [65, 66]. We could not evaluate the complication rate in infants separately although a recent unpublished report in this sub-population revealed a higher incidence (13%) compared to older children [67].

The present meta-analysis has included the maximum number of studies and patients to date. However, the study does have certain limitations. Firstly, there is a varied length of follow-up among participants in the studies, which may lead to the observation of additional complications not documented in long-term follow-up. Additionally, the rate of observed complications may also differ between studies.

Secondly, differences in resources among hospital set-ups may result in variations in the experiences of gastroenterologists who performed ERCP between studies. This could potentially impact the outcomes and conclusions drawn from the analysis. Furthermore, there is a limited number of published studies involving younger children and infants, making it unclear if success rates and complications differ in this age group compared to older children. This lack of data raises questions about generalizability and applicability to pediatric populations. Lastly, none of the included studies have mentioned mortality following ERCP, either immediately after the procedure or due to long-term complications. This information is crucial for a comprehensive understanding of the risks associated with ERCP. Overall, while this meta-analysis provides valuable insights into ERCP outcomes based on existing literature, these limitations should be taken into consideration when interpreting the results and applying them to clinical practice.

Conclusion

ERCP appears to be performed safely in children with similar success rates as in the adult population.

Availability of data and materials

Data is available upon request from the corresponding author for the article due to privacy / ethical restrictions.

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Acknowledgements

This research project has been funded by Clinical Reseach Development Center, Mofid Children's Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. and the National Agency for Strategic Research in Medical Education. Tehran. Iran. Grant No 992942.

We express our gratitude to the participants of this study.

Funding

No funding.

Author information

Authors and Affiliations

  1. Pediatric Gastroenterology, Hepatology, and Nutrition Research Center, Research Institute for Children’s Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Amirhossein Hosseini, Aliakbar Sayyari, Saleheh Tajalli & Somaye Fatahi

  2. Student Research Committee, Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Mohammad Hassan Sohouli

  3. Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran

    Elham Sharifi

  4. Department of Pharmacology and Therapeutics, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Bahrain

    Kannan Sridharan

  5. School of pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Negar Imanzadeh

  6. Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Somaye Fatahi

Authors
  1. Amirhossein Hosseini
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  2. Mohammad Hassan Sohouli
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  4. Aliakbar Sayyari
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  6. Saleheh Tajalli
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  8. Somaye Fatahi
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Contributions

S.F. and A.H. contributed to the conception, design, and statistical analysis. MH.S., E.SH., A.S., S.T., N.I., and S.F. contributed to data collection and manuscript draft. S.F and A.H contributed to the manuscript draft and critical revision. All authors approved the final version of the manuscript.

Corresponding author

Correspondence to Somaye Fatahi.

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Ethics approval and consent to participate

This study was approved by the research council and ethics committee Shahid Beheshti University of Medical Sciences, Tehran, Iran.

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The authors declare no competing interests.

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Hosseini, A., Sohouli, M.H., Sharifi, E. et al. Indications, success, and adverse event rates of pediatric endoscopic retrograde cholangiopancreatography (ERCP): a systematic review and meta-analysis. BMC Pediatr 23, 596 (2023). https://doi.org/10.1186/s12887-023-04392-5

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  • DOI: https://doi.org/10.1186/s12887-023-04392-5

Keywords

BMC Pediatrics

ISSN: 1471-2431

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