Therapeutic Endoscopic Retrograde Cholangiopancreatography for Pediatric Hepato-Pancreato-Biliary diseases: A Systematic Review and Meta-analysis

Methods

This systematic review protocol was prospectively registered (PROSPERO ID: CRD42022302911). The review is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement^[1].

Search strategy:

This systematic literature search was conducted in the PubMed、Embase、Web of Science and the Cochrane library databases to identify all relevant articles published from inception to February 2021 that evaluated therapeutic ERCP in pediatric patients with Hepato-Pancreato-Biliary diseases. Trial registers websites such as ClinicalTrials.gov and WHO ICTRP were also searched. The following terms were searched: (“Pediatrics”[Mesh] OR “Child”[Mesh] OR “Adolescent”[Mesh] OR “Infant”[Mesh] AND “Cholangiopancreatography, Endoscopic Retrograde”[Mesh] AND “Therapeutics”[Mesh]). Hepato-Pancreato-Biliary diseases were included in the search results. To be as comprehensive as possible, the search was not restricted to any study types. We also hand-searched reference lists of candidate articles to find articles that may have been missed during the literature search. Our whole search strategy for all databases is described in Supplementary Material.

Selection criteria:

Study inclusion criteria included the following: (1) the patients were less than 18 years old; (2) the patients underwent therapeutic ERCP procedures; (3) the patients all had Hepato-Pancreato-Biliary diseases; (4) the procedural success rate and adverse events rate was assessed in the studies; (5) they have detailed description and statistics of various specific treatment methods; (6) they were randomized controlled trials, case-control studies, or cohort studies.

We excluded the studies that were (1) case reports and case series, which particularity can’t represent the general outcome, and their sampling population is too small to perform meta-analysis; (2) editorial letters, expert opinions, review papers, and meta-analysis as to avoid erroneous weighting towards more frequently cited articles; (3) conference abstracts which could not obtain their full study reports as their scientific rigorousness had not been peer-reviewed; (4) endoscopic nasobiliary drainage(ENBD) or endoscopic ultrasound-guided biliary drainage (EUS-BD) were the only therapeutic methods. (If ERCP had been included in these studies, the data about ERCP alone was extracted); (5) pertinent data (such as the percentage of therapeutic interventions in all ERCP procedures, procedural success rates, and adverse events rates) were not available; (7) the cases included were not Hepato-Pancreato-Biliary diseases; (6) not English-language articles.

If similar articles containing the same population or duplicated cases were available from a single-center, we included the article which (1) contains the most comprehensive detail of study characteristics; (2) dataset has the largest sample; (3) was the most recently published one for our review.

All articles searched through the four databases were imported into Endnote for screening. Two independent reviewers (Sun, R. and Xu, X.) screened all articles relevant to therapeutic ERCP for Pediatric HPB diseases for methodological validity, and a third reviewer (Zheng, Q.) resolve the discordance during the study. Titles, abstracts, and keywords were evaluated firstly, full texts of the articles were retrieved and evaluated for eligibility after the initial screening. Two reviewers (Sun, R. and Zheng, Q.) assessed the quality measures for included studies, and discrepancies were adjudicated via consensus or referral to a third reviewer (Xu, X.) .

Data extraction:

Data from the included studies were extracted into a standard form, detailing the first author(s), publication year, country, study design, study population, number of therapeutic ERCP-procedures, procedural success rates, and adverse events rates. The number or rate of different therapeutic procedures was also extracted. We contacted the authors of the articles for confirmation or correction when there was missing or unclear information in the paper. Data extraction was carried out using Microsoft Excel (Microsoft, Redmond, Washington).

Outcome Measures:

Significant variations in study design and reporting among included publications precluded the use of a standard definition for the procedural success and post-ERCP adverse events. In our review, Procedural success was defined as the successful completion of the determined treatment of desired endoscope therapeutic intervention, or clinical condition improvement (symptoms relief or improvement after the procedure intervention). Adverse events were defined as the overall complications (such as pancreatitis, perforation, bleeding) that patients’ treatment should be altered, which means more diagnostic investigation, prescription of antibiotics, prolongation of hospitalization, subsequent surgery, or re-admission were needed^[12]. Death is one of the extremes included.

Bias assessment:

The probability of publication bias was assessed through visual inspection of funnel plots and Egger’s regression intercept.

Statistical analysis:

This is a meta-analysis of proportions, which was performed by using the Metan program with STATA Version 16 (StataCorp LP, College Station, Texas). We provide an overall estimation of the usage percentage of therapeutic interventions in all ERCP procedures, therapeutic procedure success rates, adverse events rates, and distribution of different therapeutic interventions. Because of the significant variability between studies, a random-effects meta-analysis was chosen over a fixed-effects meta-analysis using the restricted maximum likelihood method. 95% CIs were calculated initially for the rate of each statistical result from the studies. The I² statistic was used to evaluate the variance attributable to the heterogeneity between individual studies. I² < 25% was considered no heterotrophy, I² between 25% and 50% was defined as low heterotrophy, I² between 50% and 75% was defined as moderate heterotrophy, I² > 75% was defined as great heterotropy^[16].

To find out the source of high heterogeneity, secondary analyses were performed to further investigate the influence factors. A subgroup analysis was performed based on various countries, types of diseases, year of publication, and design of the study. A sensitivity analysis of all studies was also performed to exclude papers deemed to be outliers. Outliers papers were identified based on the findings from the inclusive overall estimation.

Quality assessment:

The quality of all 33 non-randomized studies included was assessed according to the Newcastle-Ottawa scale (NOS) (Table 1). NOS assessment tool is based on a star grading system which includes 3 categorical criteria. According to this standard scoring algorithm, prospective and cross-sectional studies can award a maximum of 9 scores, case-control studies can award a maximum of 10 scores. Studies that received a score of above 6 were deemed as high quality. Two reviewers (Sun, R. and Xu, X.) independently assessed the study quality using this format, and disagreements were solved by the other author (Zhan, J.).

Table 1

the Newcastle-Ottawa scale(NOS) of studies included.
Study	Selection 1 2 3 4	Comparability 1 2	Outcome assessment 1 2 3	Total Score
Barakat et al. (2021)	+ + + +		+ + +	7
Mercier et al. (2021)	+ +	+	+ + +	6
Lin et al. (2021)	+ + + +		+ + +	7
Asenov et al. (2019)	+ + +	+	+ +	6
Harputluoglu et al. (2019)	+ + + +	+	+ + +	8
Wen et al. (2019)	+ + + +		+ + +	7
Zeng et al. (2019)	+ + +	+	+ + +	7
Kohoutova et al. (2019)	+ + +		+ + +	6
Czubkowski et al. (2018)	+ + +	+	+ + +	7
Rosen et al. (2017)	+ + + +	+	+ + +	8
Giefer et al. (2015)	+ + +	+ +	+ + +	8
Dechêne et al. (2015)	+ + +	+	+ +	5
Kargl et al. (2015)	+ + +		+ + +	6
Agarwa et al. (2014)	+ + +	+	+ + +	7
Oracz et al. (2014)	+ + +		+ + +	6
Steen et al. (2013)	+ + +	+	+ +	6
Tsuchiya et al. (2013)	+ + +		+	5
Limketkai et al. (2013)	+ + +	+	+ +	6
Enestvedt et al. (2013)	+ + +		+ + +	6
Otto et al. (2012)	+ + + +	+	+ +	7
Berquist (2012)	+ + +	+	+	5
Otto et al. (2011)	+ + + +		+ + +	7
Jang et al. (2010)	+ + +	+	+ + +	7
Li et al. (2010)	+ + + +	+	+ + +	8
Vegting et al. (2009)	+ + +	+	+ +	6
Issa et al. (2007)	+ + +		+ + +	6
Rocca et al. (2005)	+ + +	+	+ + +	7
Cheng et al. (2005)	+ + + +	+	+ + +	8
Varadarajulu (2004)	+ + + +		+ + +	7
Pfau et al. (2002)	+ + +		+ + +	6
Poddar et al. (2001)	+ + +	+	+ + +	7
Hsu et al. (2000)	+ + + +		+ + +	7
Guelrud et al. (1994)	+ + +		+ + +	6
Selection:
1、Representativeness of the exposed cohort
2、Selection of the non exposed cohort
3、Ascertainment of exposure
4、Demonstration that outcome of interest was not present at start of study
Outcome assessment:
1、Assessment of outcome
2、Follow-up long enough for outcomes to occur
3、Adequacy of follow up of cohorts
Comparability: study controls for the most important factor or any additional factor

Results

Literature Search Results:

We initially search 3897 results, the process was revealed in the PRISMA flow diagram (Fig. 1). The search retrieved 2061 results from Pubmed, 283 results from Web of Science, 1512 results from Embase, 36 results from Cochrane, 5 results from Registers. All articles were imported into endnote for screening after 653 duplicate records were removed. After the first round by reviewing the title and abstracts, 3244 studies were removed. In 294 Reports sought for retrieval, 1 was not retrieved. In the second round, 293 reports were assessed for eligibility, 74 results were review, systematic review and meta-analysis, 182 results were Case reports, and 4 results were Not published in English. Finally, 33 articles were included in the review.

Study characteristics:

A total of 33 articles were included (Table 2), studies included were retrospective studies and prospective studies, which involve 2 multicenter studies. A total of 13053 therapeutic ERCPs were performed on 14162 children and adolescents. The median patient number of each study is 396, and it ranges from 12 to 11060. Most studies were conducted on minimally invasive therapy for the HPB system, which indications include all pediatric hepatic, pancreatic and biliary diseases. Some other studies were only performed on a single condition, such as pancreatic diseases, symptomatic pancreaticobiliary maljunction (PBM), and complications after liver, intestine, or composite abdominal organ transplantation. Studies cover Occident (the United States, France, Belgian, etc) and Orient (China, Japan, Korea, etc) countries. 20 studies have been conducted over the last decade, the other 13 studies were performed before that. 7 articles didn’t report the total number of ERCP procedures, 8 articles didn’t report the procedural success rates, and 3 articles didn’t report the adverse events rates. 24 papers present the classification of specific therapeutic methods and only 10 of them clarify the percentage of each treatment in all therapeutic procedures (Table 3). Because of the diversity of diseases classification and complexity of specific therapeutic treatment, sex and age stratification were not included in the study.

Table 2

Characteristics of included studies.
Citation	Country	Study design	Study population n	Disease		Procedural success rates % (n)	Adverse events rates % (n)
Barakat et al^[17] (2021)	United States	Retrospective study	11060	HPB diseases	9456/11060 (85.49%)	N/A	N/A
Mercier et al^[2] (2021)	France and Belgian	Retrospective multicentre cohort study	271	HPB diseases	423/470 (90%)	60% (193/320)	19% (65/340)
Lin et al^[18] (2021)	United States	Retrospective study	27	PD	58	65% (13/20)	21% (12/58).
Asenov et al^[19] (2019)	Turkey	Retrospective study	24	HPB diseases	17/35 (49%)	71% (17/24)	4% (1/25)
Harputluoglu et al^[6] (2019)	Turkey	Retrospective study	49	Biliary complications after duct-to-duct biliary anastomosis in LT	49	63.3% (31/49)	N/A
Wen et al^[20] (2019)	China	Retrospective study	38	PD presenting with AP/CP	74	93.2% (69/74)	14.9% (11/74)
Zeng et al^[21] (2019)	China	Retrospective multicenter study	75	Symptomatic PBM	112	82.4% (56/68)	75%
Kohoutova et al^[22] (2019)	Italy	Retrospective study	38	CP	119/158(75.3%)	74%	3%
Czubkowski et al^[9] (2018)	Poland	Retrospective study	30	Biliary strictures after pediatric LT	95	73% (22/30)	17.9% (17/95)
Rosen et al^[23] (2017)	United States	Retrospective cohort study	184	HPB diseases	168/215 (78%)	N/A	10.4% (22/212)
Giefer et al^[24] (2015)	United States	Retrospective study	276	HPB diseases	345/425 (81.3%)	N/A	7.7% (26/338)
Dechêne et al^[5] (2015)	United States	Retrospective study	17	Biliary complications after LT	13/61(21.3%)	N/A	23.5%
Kargl et al^[25] (2015)	Austria	Prospective study	12	hereditary pancreatitis	25/30 (83.3%)	83.3% (10/12)	16.7% (2/12)
Agarwal et al^[26] (2014)	India	Retrospective study	172	pancreatic disorders	205/221 (92.8%)	64.9%	4.7%
Oracz et al^[27] (2014)	Poland	Retrospective study	208	CP	223/481 (46.4%)	98.7% (475/481)	1.9% (9/481)
Steen et al^[14] (2013)	Netherlands	Retrospective study	13	biliary complications after partial liver resection	10	60%	10.8%
Tsuchiya et al^[28] (2013)	Japan	Prospective study	55	CC	13/55 (23.6%)	84.6%	N/A
Limketkai et al^[29] (2013)	United States	Retrospective cross-sectional study	154	HPB diseases	247/289 (85.5%)	90.7%	5.9%
Enestvedt et al^[30] (2013)	United States	Retrospective study	296	HPB diseases	275/429 (64.1%)	95.2%	17.5%
Otto et al^[31] (2012)	United States	Retrospective study	25	HPB disease following abdominal organ transplant	42/48 (87.5%)	N/A	2.08%
Berquist^[32] (2012)	United States	Retrospective study	25	HPB complications after liver, intestine, or composite visceral transplantation	37/48 (77%)	N/A	2.9%
Otto et al^[11] (2011)	United States	Retrospective study	167	HPB diseases	159/231 (68.8%)	N/A	4.76% (11/231)
Jang et al^[33] (2010)	Korea	Retrospective study	122	HPB diseases	190/245 (77.6%)	98.4% (241/245)	18.3% (45/245)
Li et al^[34] (2010)	China	Retrospective study	51	CP	110	71.4% (30/42)	17.3% (19/110)
Vegting et al^[35] (2009)	Netherlands	Retrospective study	61	HPB diseases	60/99 (60.6%)	71% (70/99)	4% (4/99)
Issa et al^[36] (2007)	Saudi Arabia	Retrospective study	125	HPB diseases	63/122 (51.9%)	96.8%	3.2%
Rocca et al^[13] (2005)	Italy	Retrospective study	38	HPB diseases	33/48 (68.75%)	97.9%	6% (3/48)
Cheng et al^[37] (2005)	United States	Retrospective study	245	HPB diseases	235/329 (71.4%)	97.9%	9.7% (32/329)
Varadarajulu et al^[38] (2004)	England	Retrospective case-controlled study	116	HPB diseases	110/163 (67.4%)	97.5% (161/163)	3.4% (3/163)
Pfau et al^[39] (2002)	United States	Retrospective study	43	HPB diseases	24/53 (45%)	94.3%	12.5% (3/24)
Poddar et al^[15] (2001)	India	Retrospective study	72	HPB diseases	22/84 (26.2%)	N/A	8% (6/75)
Hsu et al^[40] (2000)	United States	Retrospective study	22	Pancreatitis	23/34 (67.6%)	73.3% (11/15)	6% (2/34)
Guelrud et al^[41] (1994)	venezuela	Retrospective study	51	Idiopathic recurrent pancreatitis	18/37 (49%)	83% (15/18)	16.6% (3/18)
HPB: Hepato-Pancreato-Biliary; PD: Pancreas divisum; LT: liver transplantation; AP:acute recurrent; CP: chronic pancreatitis; PBM:pancreaticobiliary maljunction; CC:Choledochal cysts.

Table 3

Random-effects meta-regression to investigate the reason for heterogeneity of the percentage of therapeutic interventions in all ERCP procedures.
_meta_es	Coef.	Std. Err.	z	P>\|z\|	[95%Conf.Interval]
Countrysubtype	.0597887	.0386503	1.55	0.122	− .0159645 .1355418
Diseasesubtype	.0097363	.0140803	0.69	0.489	− .0178605 .0373331
Yearsubtype	− .0744469	.0267981	-2.78	0.005	− .1269702-.0219237
Studydesignsubtype	.0334285	.0718178	0.47	0.642	− .1073317 .1741887
_cons	.7616619	.0937192	8.13	0.000	.5779758 .9453481
Test of residual homogeneity: Q_res = chi2(5) = 5.47 Prob > Q_res = 0.3618.
Number of obs = 10
Method: REML
Residual heterogeneity:
tau2 = .000253
I2 (%) = 16.62
H2 = 1.20
R-squared (%) = 78.08
Wald chi2(4) = 10.07
Prob > chi2 = 0.0393
Countrysubtype:
1: Occident countries(the United States, France, Belgian, etc)
2: Orient countries (China, Japan, Korea, etc)
Diseasesubtype:
1: HPB system diseases, which include all pediatric hepatic, pancreatic and biliary diseases
2: Pancreatic diseases
3: Hepatobiliary diseases
4: Complications after liver, intestine, or composite abdominal organ transplantation
Yearsubtype:
1: Publications in the last 10 years(2012 ~ 2022)
2: Publications in the last 10 to 20 years(2002 ~ 2012)
3: Articles published 20 years ago
Studysubtype:
1: Retrospective study
2: Prospective study

Table 4

Distributions of various therapeutic procedures.
	Sphincterotomy	Stone extraction/removal	Stent placement	bougienage /Balloon dilation	Bile/pancreatic duct drainage
Wen et al. (2019)	39.2% (29/74)	4.0% (3/74)	10.8% (8/74)	29.7% (22/74)	N/A
Kargl et al. (2015)	32% (8/25)	20% (5/25)	32% (8/25)	20% (5/25)	N/A
Giefer et al. (2015)	51% (176/345)	35.9% (124/345)	58.3% (201/345)	27% (93/345)	N/A
Dechêne et al. (2015)	69.2% (9/13)	46.2% (6/13)	76.9% (10/13)	92.3% (12/13)	N/A
Oracz et al. (2014)	31.4% (70/223)	33.6% (75/223)	100% (223)	24.7% (55/223)	N/A
Limketkai et al. (2013)	44.9% (111/247)	28.3% (70/247)	43.3% (107/247)	7.7% (19/247)	N/A
Enestvedt et al. (2013)	68% (187/275)	40.7% (112/275)	42.9% (118/275)	13.8% (38/275)	N/A
Cheng et al. (2005)	76.2% (179/235)	18.3% (43/235)	57% (134/235)	1.7% (4/235)	2.1% (5/235)
Pfau et al. (2002)	95.8% (23/24)	58.3% (14/24)	37.5% (9/24)	N/A	N/A
Poddar et al. (2001)	4.5% (1/22)	N/A	22.7% (5/22)	4.5% (1/22)	72.7% (16/22)
n, number; N/A, not available

The percentage of therapeutic interventions in all ERCP procedures:

To explore the using ratio of ERCP as a minimal interventional therapy, 26 studies were included initially, and the overall pooled percentage of therapeutic interventions in all ERCP procedures is 66% ( 95% CI 58%-73%), heterogeneity among the studies is significant (I² = 98.74%). After sensitivity analysis, we excluded articles with high heterogeneity, and 10 articles were included finally in the result. The usage rate of therapeutic ERCP is 77% ( 95% CI 74%-81%), which is higher than before (Fig. 2). A good symmetry can be roughly seen from the funnel plot, suggesting that there is no significant publication bias. However, some points fall outside the funnel plot, indicating that heterogeneity still exists (Fig. 3). Regression-based Egger test for small-study effects shows that P = 0.6654, which represents there is no significant publication bias and small-study effects. This analysis is a confirmation of the stability in our result. Although heterogeneity has been minimized to 49.35%, which is low heterogeneity, we conduct meta-regression to investigate the reason for the difference (Table 3). The results show that the time of publication (yearsubtype P = 0.005) is the cause of heterogeneity. We then performed a subgroup analysis on the year of publication and found that heterogeneity was indeed reduced in all groups. Especially in the studies published in the last decade (2012–2022), the result is 80% (95% CI 77%-83%), which is relatively representative (Fig. 4).

Therapeutic procedure success rates and adverse events rates:

Among the studies which reported the success rates of the therapeutic procedure, heterogeneity among the studies originally included is significant. To investigate the source of heterogeneity, we performed various studies. We divided countries into Occident and Orient countries. We divided diseases into the overall HPB diseases, pancreatic diseases, biliary diseases, and HPB complications after organ transplantation. The year of publication was divided into the last decade, two decades, and two decades ago. Univariate Random-effects meta-regression analysis shows that country (P = 0.821), disease (P = 0.453), and the publication year (P = 0.596) are not the source of heterogeneity, multiple meta-regression analysis shows that R-squared (%) < .001, which indicates that the model constructed by these three variables is invalid. Subgroup analysis showed the same result because heterogeneity was not well reduced according to the outcome of these three classifications. Nonparametric trim-and-fill analysis of publication bias indicates that after input 5 studies, the therapeutic procedure success rate is 87.4% (95% CI 79.4%-95.4%) (Fig. 5). Sensitivity analysis results show the study has a significant effect on the heterogeneity. Based on the above analysis, 5 studies were deemed as outlier studies (Fig. 6). After the exclusion of relevant studies, the overall pooled estimates that therapeutic procedure success rate is 74% ( 95% CI 69%-79%), I² = 18.08% (Fig. 7).

Of the studies which represent the adverse rates. Regression-based Egger test for small-study effects shows that P = 0.001, which represents the existence of publication bias. Nonparametric trim-and-fill analysis of publication bias indicates that after input 7 studies, therapeutic procedure adverse rates is 5.6% ( 95% CI 2.1%-9.1%. After sensitivity analysis, 10 outlier studies were excluded. The overall pooled therapeutic adverse events rate is 8% ( 95% CI 6%-10%), I² = 20.25% (Fig. 8).

Distribution of different therapeutic procedures:

With the advancement of endoscopic manipulation techniques, more different treatments are performed in the therapeutic process. We analyzed several main treatment methods. Results from 3 studies showed that pooled overall usage reveals that the rate of stent placement is 75% (95% CI 65%-86%), I² = 0.00% (Fig. 9). Similarly, pooling studies we found that the usage rate of sphincterotomy (ST), stone extraction/removal, bougienage /Balloon dilation, which is respectively 46% ( 95% CI 39%-53%), I² = 56.5%, 34% ( 95% CI 31%-38%), I² = 0.01%, and 26% ( 95% CI 22%-29%), I² = 0.01% (Fig. 10–12), as demonstrated in the forest plot after excluding papers which have high heterogeneity.

Discussion

HPB diseases have been diagnosed increasingly in the pediatric group. The advancement of special appropriately-sized pediatric endoscopes contributes to the expanded utilization in children. Cohort studies and case reports in children have been described in this field recently. However, data on ERCP therapy is still scarce owing to the technical difficulty of performing intervention in pediatric cohorts and there is no comprehensive study because of the historically limited research. Therefore, the efficacy and safety are still contentious. To guide the further development of clinical work, the therapeutic role of ERCP in children should be demonstrated. ERCP is generally accepted as a therapeutic technique, the proportion of therapeutic ERCP in all procedures is 77% demonstrated in our study. Subtype analysis shows that the proportion of use is increasing by the year. In the last decade, it is roughly 80% of total usage, 74% in the last 10 to 20 years, and only 68% 20 years ago. It reflects that this operation modality has clinical value and is being used by more clinical centers in treating pancreaticobiliary disorders in children.

There is a significant difference between children and adults in the type of anesthesia and the type of duodenoscope^[42]. ERCP in small children was often performed under general anesthesia with endotracheal intubation. Compared with other gastrointestinal (GI) endoscopies, ERCP has a higher rate of complications, so careful selection of ERCP for therapeutic purposes is essential. With the technological improvements of noninvasive imaging studies, it is gradually replaced by Magnetic resonance cholangiopancreatography (MRCP). Though this cross-sectional imaging modality has no ionizing radiation and does not need intravenous contrast, it has some limitations. For example, it has a complementary lower resolution for discerning minor ductal anatomy and abnormalities compared with ERCP. ERCP has been well-defined for its diagnostic role in detailed information. Currently, it is mostly chosen as a therapeutic approach allowing direct visualization of biliary pancreatic duct structure. Specialized fiberoptic duodenoscope is generally used in patients younger than 1 year old^[42]. A systematic review and meta-analysis of Single-balloon enteroscopy (SBE)-assisted ERCP on adult biliary interventions is reported that pooled procedural success rate was 75.8% (95% CI 71.0%-80.3%)^[43]. Its feasibility in pediatric patients with surgically altered gastrointestinal anatomy has also been reported recently^[44]. Therapeutic ERCP procedures may be a beneficial and alternative treatment for HPB diseases, which success rate in our study is 74%, especially for pediatric patients, because there are considerable risks for them during surgical operations. By analyzing the influencing factors, country, disease, and publication year don’t affect the rate of therapeutic success. By sensitivity analysis, we found that most of the studies that cause heterogenity have a larger sample size. The study Mercier(2021)which has the greatest heterogeneity is a recently published large sample multicentre cohort study. In this study, ERCP was therapeutic in 90% of included cases, and the overall complication rate was 19%^[2]. Compared with other included studies, it may have represented the rapid development of therapeutic ERCP technique, comprehensive results of multiple diseases, and the proficiency of doctors in French and Belgian children’s medical centers.

Surgical management may create an extra scar and lead to the necessity for tube management. Preoperative ERCP before surgery may also benefit HPB patients, it can serve as a transitional step to definitive surgery by relieving clinical symptoms. The therapeutic management of HPB diseases by ERCP before laparoscopic is effective in many conditions. In our study, the pooled overall usage rate of stent placement is 75%, and the usage rate of sphincterotomy, stone extraction/removal, bougienage /Balloon dilation, which is respectively 46%, 34%, and 26%. EST or biliary drainage by ERCP has minimal invasiveness and a shorter operating duration. Ductal drainage is an effective therapeutic goal to redress elevated intra-organic pressure, which can reduce pain and recurrence. The goal of endoscopic interventions is reducing pressure in the damaged biliary or pancreatic duct system, early drainage is the main prerequisite for the spontaneous closure of the leak. Most patients benefit from sphincterotomy, EPS, or stent placement fluid drainage to pancreaticobiliary duct decompression. At present, endoscopic drainage of pancreatic ducts is accepted as a viable option of pain management in the majority of cases, precludes the need for surgery.

Ductal obstruction and ductal disruption (pancreaticobiliary duct leak, ductal stricture, and residual stone diseases) were routinely treated by duct stent placement. In our study, it is the most common usage which accounts for 75% of all therapeutic procedures. A recent study shows the temporary use of fully covered self-expandable metal stents (FC-SEMSs) for recurrent benign main pancreatic duct (MPD) strictures in children is feasible and safe^[3]. However, in many other cases, such as post-traumatic duct disruption can be definitely managed by temporary stenting. Emergent excision may be dangerous, except when precise pancreaticobiliary anatomy is obtained. Under such particular circumstances, appropriate sphincterotomy can treat duct obstruction^[8]. Prophylactic or therapeutic stent placement may be associated with a higher rate of Post-ERCP pancreatitis (PEP), which was demonstrated by a univariate analysis^[2]. Long-term management is required by exchanging the stent.

If bile leakage was detected on ERCP, a stent was inserted to drain the leak. If stones were found by ERCP, a basket catheter can be used to extract the stone. Percutaneous drainage with transhepatic biliary interventions (PTBI) and surgical treatments was considered only if the ERCP procedure is failed. For patients with persistent or exacerbated symptoms, we have tentatively been adopting external biliary drainage, including percutaneous transhepatic biliary drainage or open T-tube drainage. External drainage immediately relieves the symptoms and has the advantage of facilitating thorough examinations of the pancreaticobiliary system until definitive surgery can be undertaken. When percutaneous drainage is not effective, a more invasive technique may be necessary. Early and sufficient endoscopic drainage can optimize patients’ condition before definitive surgery, some patients are even not required to undergo a subsequent operation. Data from large cohorts indicate that the pediatric population would benefit from primary endoscopic management as a more definitive option compared with a primary surgical approach. The treatment success rate was significantly higher in the ERCP alone group compared with patients managed operatively. What is noteworthy is duodenal perforation, which is the most dangerous complication, as a result of the discrepancy between the size of the duodenoscope and duodenum. It should be mainly resolved by surgery. In other cases, surgery should only be performed as a last resort.

During the process of discussing the heterogenity of procedure success rate by disease subtype analysis, we found I² of HPB complications after organ transplantation group is only 23.87%. This suggests that there may be a subgroup of diseases that will benefit similarly from therapeutic ERCP. Biliary complications(BC) are common in the pediatric population after liver transplantation because split or reduced-size living donor grafts are frequently used. Despite there is progress in surgical procedures, anastomotic biliary strictures (ABS), leaks, and other complications often cause graft loss and high morbidity. The type of liver graft or abdominal organ transplant may cause different complications. Percutaneous and surgical drainage are general managements, endoscopic interventions also have been reported to have successful outcomes in children^[5]. Endoscopic biliary stenting (EBS) drainage with FC-SEMSs or plastic stent (PS) has been reported potentially efficient for ABS after liver transplantation in adults^[4]. Although Endoscopy has replaced surgery in most patients with ABS, approximately 10%~20% of patients require surgical revision in the long run^[9]. When access to the strictures in the peripheral biliary tree is not possible with ERCP, the rendez-vous technique (PTBD + ERCP) may be useful to insert the stent through the stricture^[10]. A nasobiliary drain (NBD) is less effective than internal stenting, because the size of the biliary tract in children is too small for the tube to insert into, and the drain becomes dislodged easily. Patients with clinical symptoms initially receive an abdominal ultrasound to evaluate the sign of the presence of a biliary tract stricture. Then a cholangiogram by PTC can demonstrate the presence of caliber changes in the biliary tract. During PTC dilation the stent placement can be performed. If this is not successful, dilation and stent placement can be performed by ERCP^[14]. Some children have a functional disorder, where ERCP is unlikely to demonstrate any organic lesion. In such children, MRCP may be a more appropriate investigation^[15].

High adverse rate due to complexity and uniqueness remains an issue. The adverse rate of ERCP is higher when the procedure includes a therapeutic intervention than when it is used for diagnosing purposes. In our study, the pooled therapeutic adverse events rate is 8%, which is higher than the overall complication rate of 4.76%^[11]. Pediatric patients all have the need for repeated treatment sessions under general anesthesia. Percutaneous procedures may cause perforation, bleeding, and bacteremia. Transplanted children who have smaller liver volumes need larger radiation doses and longer fluoroscopy times. These all seriously influence the quality of life. It may also have an omission of intrahepatic biliary dilatation. Surgical treatment is the most invasive procedure and is often performed after the failure of endoscopic and percutaneous interventions^[6]. Early ERCP, proceeding with a step-up strategy from drainage procedures to surgical treatment when it is required due to unsatisfactory results. So far, surgery has no longer been the mainstay for the treatment. To achieve symptomatic improvement, doctors should eliminate the need for surgery in selected patients.

There should be evidence-based guildelines to recommend the therapeutic ERCP procedure which will specifically benefit pediatric patients. Endoscopists specialized in evaluating pediatric patients usually function as members of a multidisciplinary team. To yield better outcomes, decrease the number of hospitalizations and surgical interventions, every step of the process, from preparation to subsequent treatment should be performed in close collaboration with anesthesiologists, pediatricians, pediatric surgeons, and gastroenterologists. The combination of laparoscopic general surgery and advanced endoscopy is more promising.

The limitations of our study should be acknowledged: The outcomes of pediatric ERCP performed by surgical versus medical specialties are different. Small versus large patient volume health care facilities should be compared. Robust volume outcomes should be obtained from a larger population. Pediatric ERCP had different roles in disparate age groups, so age stratification is also a potential influence factor^[45]. Childhood covers a broad continuum of physical development, where anatomic and physiologic considerations for endoscopy may dramatically vary among age groups. For instance, infants and toddlers have a greater theoretical risk of tracheal compression and oxygen desaturations during the endoscope treatment. Likewise, younger children typically require deeper sedation and are more sensitive to weight-based medication dosing than teenagers or adults. Teenagers, whose physical attributes more closely resemble those of young adults, need no special pediatric endoscope. There may be opposite treatment in infants younger than 12 months of age. A comprehensive assessment of these data may help expand the awareness of pediatric surgeons in the usage of minimally invasive techniques to treat HPB diseases and contribute to the improvement of therapeutic methods and enhance the utilization rate in this field.

Our analysis indicated that ERCP is an effective treatment option for pediatric HPB diseases. Given the above analysis, we deem it reasonable to perform therapeutic ERCPs to achieve long-term remission. Further study should have taken place to decipher the feasibility of therapeutic ERCP in children.

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