Systematic Appraisal of Guidelines for the Diagnosis and Treatment of Choledocholithiasis

Abstract

Background:

To systematically evaluate the methodological quality of the current up-to-date guidelines pertaining to choledocholithiasis, we conducted a comprehensive analysis of key recommendations and corresponding evidence, focusing on the heterogeneity among these guidelines.

Method:

Systematic searches across various databases were performed to identify the latest guidelines. The identified guidelines, which met the inclusion criteria, underwent evaluation using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool. The key recommendations and evidence from the included guidelines were extracted and reclassified using the Oxford Centre for Evidence-Based Medicine (OCEBM) grading system, and the obtained results were analyzed.

Results:

Nine guidelines related to choledocholithiasis were included in this study, out of which 4 achieved an overall standardized score of more than 60%, indicating their suitability for recommendation. Upon closer examination of the main recommendations within these guidelines, we discovered significant discrepancies concerning the utilization of similar treatment techniques for different diseases or different treatment methods under comparable conditions, and discrepancies in the recommended treatment duration. High-quality research evidence was lacking, and some recommendations either failed to provide supporting evidence or cited inappropriate and low-level evidence.

Conclusion:

The quality of guidelines pertaining to choledocholithiasis is uneven. Recommendations for the treatment of choledocholithiasis demonstrate considerable disparities among the guidelines, particularly regarding the utilization of endoscopic retrograde cholangiopancreatography as a treatment method and the management approaches for difficult stone cases. Improvements by guideline developers for these factors contributing to the heterogeneity would be a reasonable approach to further update the guidelines for cholangiolithiasis.

Cholelithiasis is one of the most common biliary diseases worldwide, affecting ~1 out of 1000 people.¹ Gallstones are common (~10% to 20% of the global adult population), and >20% of people with gallstones will develop symptoms.² Most gallstones are found in the gallbladder, but sometimes they pass through the cystic duct into the extrahepatic and/or intrahepatic bile ducts and become bile duct stones.³ Choledocholithiasis can also be formed in the absence of gallbladder stones. A variety of factors can affect the formation of gallstones, including disorders of cholesterol handling, dietary habits, genetic factors, obesity, etc.^4,5

With the rapid development of endoscopic retrograde cholangiopancreatography (ERCP), laparoscopy and other technologies, the removal of bile duct stones under laparoscopy has become very common. Early diagnosis, timely treatment and correct management can greatly reduce the incidence of complications and lessen the damage of lesions to surrounding organs. Many clinical guidelines on the management of choledocholithiasis have been developed,^6–14 but there are differences in the quality of guideline development and methodological rigor. Various opinions are given on clinical issues such as how to diagnose biliary calculi, the management of patients with various biliary calculi, the use of ERCP, and the treatment of difficult calculi, which may cause confusion for guideline users. Therefore, our goal was to analyze the methodological quality of the current choledocholithiasis guidelines, reveal the heterogeneity of the recommendations across guidelines, and discuss potential causes of this heterogeneity to help clinicians choose the most appropriate guidelines and recommendations and to provide a reference for guideline developers to better update the guidelines.

METHODS

Study Design

In this study, a comprehensive quality assessment was performed by using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool, which operated in accordance with the Preferred Reporting for Systematic Reviews and Meta-analyses Protocols (PRISMA-P) principles.¹⁵

Data Sources and Literature Selection Process

Systematic searches were conducted across multiple databases, including PubMed, Web of Science, Ovid, Cochrane Library, ScienceDirect, and China National Knowledge Infrastructure (CNKI) databases. Searches were limited to documents in English or Chinese published up to July 2021. The following search terms were utilized: “choledocholithiasis”, “bile duct stone”, “bile duct calculi”, “gallstone”, “guideline”, “recommendation”, “consensus”, and “statement”. The search query was tailored to the specific requirements of each database. After the initial database searches, supplementary searches were performed on Baidu Scholar and Google Scholar. Furthermore, the official websites of guideline development organizations such as NICE (https://www.nice.org.uk/guidance), SIGN (http://www.sign.ac.uk/), GIN (http://www.g-i-n.net/), and NGC (https://www.guideline.gov/) were consulted. In addition, a manual search of the references cited in the included guidelines was conducted to identify any potential guidelines, ensuring a comprehensive and systematic search approach.

Study Selection and Extraction

The inclusion criteria were as follows: (I) guidelines for choledocholithiasis; (II) guidelines published in English or Chinese; (III) guidelines with full texts available online; (IV) guidelines for clinical doctors; and (V) if several versions were available, only the latest version was selected. The exclusion criteria were as follows: (I) duplicate guidelines; (II) meeting abstracts; and (III) summaries or assessments of guidelines. Retrieved guidelines were screened by 2 reviewers according to the above inclusion and exclusion criteria. If there was a disagreement, a third reviewer participated in the discussion to decide whether to include the guideline.

After meeting the inclusion criteria, basic information, including guideline title, author, publication year, edition, and main topic, was extracted from the eligible guidelines.

Quality Evaluation of the Guidelines

Guideline quality was assessed against the latest version of the AGREE II tool,¹⁶ which can be used to systematically assess guideline quality and has been validated in previous applications. It includes 23 items across the following 6 Domains: Domain 1, scope and purpose, addressing the guideline’s overall goals, specific health issues and target populations (Items 1 to 3); Domain 2, participants (Items 4 to 6); Domain 3, rigor of development, involving the process of gathering evidence and the methodology for developing the recommendation (Items 7 to 14); Domain 4, clarity of expression, including the language, structure and format of the guideline (Items 15 to 17); Domain 5, applicability, including possible barriers and facilitators during implementation (Items 18 to 21); and Domain 6, editorial independence, requiring that proposals not be influenced by sponsorship and clarifying conflicts of interest (Items 22 to 23). Each Domain was independently evaluated by 4 reviewers (S.Y.Z., C.Y.Z., Y.J.L., and B.Z.), and each item was scored on a 7-point scale: 1 for strongly disagree and 7 for strongly agree. The higher the score, the closer or more closely the criteria were considered. All items with a score difference of 3 points or more were discussed further. Finally, a reviewer summed all the scores for each item and calculated them by using the following formula: (actual score – minimal possible score)/(maximal possible score – minimal possible score) 100%.¹⁶ To promote consistency in the evaluation of the existing guidelines using the AGREE II tool, each guideline was classified as follows: overall scores > 60%, “strongly recommended”; scores between 30% and 60%, “recommended with modifications”; and scores < 30%, “not recommended”.

Guidelines for the Evaluation of Items and Evidence Related to Choledocholithiasis

The main recommendations in the ES guideline⁸ were extracted as a reference to compare the consistency of relevant recommendations in other guidelines (Table 1). Guidelines were scored by using a rate-of-consistency measurement scale:¹⁷

TABLE 1.

Scientific Agreement of the Formulated Recommendations for the Diagnosis and Treatment of Choledocholithiasis in the Included Guidelines

	ES (%)8	NI (%)7	AS (%)6	CR (%)12	CS (%)11	We (%)9	JS (%)10	EA (%)13	NI (%)14
Imaging examination
Liver function	─	80-100	80-100	80-100	80-100	80-100	80-100	80-100	80-100
Ultrasound	─	80-100	80-100	80-100	80-100	80-100	80-100	80-100	80-100
EUS	─	80-100	80-100	80-100	80-100	80-100	80-100	80-100	80-100
MRCP	─	80-100	80-100	80-100	80-100	80-100	80-100	80-100	80-100
ERCP	─	─	60-80	60-80	60-80	60-80	80-100	─	─
Treatment
ERCP	─	60-80	20-40	─	80-100	20-40	80-100	60-80	60-80
ERCP+LC	─	60-80	20-40	─	80-100	20-40	─	40-60	60-80
Stone extraction	─	80-100	─	─	80-100	80-100	80-100	60-80	80-100
Biliary drainage	─	60-80	60-80	─	80-100	80-100	80-100	60-80	60-80
Biliary stent for special situations	─	─	80-100	─	80-100	80-100	80-100	─	─
EPLBD+EST	─	─	60-80	─	60-80	60-80	40-60	60-80	─
Cholecystectomy	─	20-40	20-40	─	40-60	20-40	─	20-40	20-40
Cholecystolithotripsy	─	60-80	60-80	─	80-100	60-80	─	60-80	─

Measurement Scale of Rate of Agreement: 0% to 20%: Radically different; 20% to 40%: Numerous major scientific disagreements present; 40% to 60%: Few major scientific disagreements present; 60%-80%: Only minor scientific disagreements present; 80%-100%: Absolute scientific agreement. In blank fields, no information was available.

EPLBD indicates endoscopic papillary large-balloon dilation; ERCP, endoscopic retrograde cholangiopancreatography; EST, endoscopic sphincterotomy; EUS, endoscopic ultrasonography; LC, laparoscopic cholecystectomy; MRCP, magnetic resonance cholangiopancreatography.

0% to 20%: Radically different

20% to 40%: Numerous major differences

40% to 60%: Some major differences

60% to 80%: Only minor differences

80% to 100%: Essentially identical

The corresponding supporting evidence in each guideline was regraded by using the Oxford Centre for Evidence-Based Medicine (OCEBM) grading system.¹⁸

Statistical Analysis

Normalized scores for each domain were calculated using descriptive statistical analysis methods and expressed as percentages, and this study also calculated the median and range for each domain. We used 2-way analysis of variance (ANOVA) to estimate intraclass correlation coefficients (ICCs) to test whether the scores of the 4 raters were consistent. An ICC between 0.01 and 0.20 was considered a minor consistency, 0.21 to 0.40 was considered fair, 0.41 to 0.60 was considered moderate, 0.61 to 0.80 was considered substantial, and 0.81 to 1.00 was considered very good. A value of P < 0.05 was considered statistically significant. Statistical analysis was performed using IBM Statistical Product and Service Solutions (SPSS) version 26.0 (SPSS Inc.).

RESULTS

Guideline Characteristics

After the removal of duplicates, a total of 495 articles were obtained through the search process. By browsing the titles and abstracts, 37 articles were selected for full-text review. Ultimately, 9 articles met the inclusion criteria (Fig. 1). Table 2 presents the key characteristics of the included guidelines in this study. The selected guidelines were published between 2014 and 2021, with 2 originating from Europe,^8,13 1 from the United States,⁶ 2 from China,^11,12 3 from the United Kingdom,^9,14 and 1 from Japan.¹⁰ Seven of the guidelines were updates to the previous version,^6–12 and the other 2 were original versions,^13,14 both published by associations of medical organizations.

FIGURE 1.

Flow chart of study selection.

TABLE 2.

Characteristics of the Included Guidelines

Guideline ID	Short name	Development organization	Country applied	Version	Grading system	Topic	Development method
NICE, 20217	NI	NICE	UK	Updated	Grade	Gallstone disease overview	EB
ESGE, 20198	ES	ESGE	European	Updated	Grade	Provides practical advice on how to manage patients with CBDS	EB
ASGE, 20196	AS	ASGE	America	Updated	Grade	Provides evidence-based recommendations for the endoscopic evaluation and treatment of choledocholithiasis	EB
CRHS, 201912	CR	CRHS	China	Updated	Grade	Provides guidelines for minimally invasive surgery for hepatolithiasis	EB
CSDE, 201811	CS	ERCP Group, CSDE	China	Updated	Grade	Standardizes the surgical process and promotes the use of ERCP	EB
Williams et al, 20179	We	None	UK	Updated	Grade	Provides updated guidance on treating CBDS to health care professionals	EB
JSGE, 201610	JS	JSGE	Japan	Updated	Grade	Describes the clinical management of cholelithiasis and its complications	EB
EASL, 201613	EA	EASL	European	Original version	Grade	Provides recommendations on the prevention, diagnosis and therapy of gallstones	EB
NICE, 201414	NI	NICE	UK	Original version	Grade	Provides recommendations about how gallstone disease should be identified, diagnosed and managed in adults	EB

ASGE indicates American Society for Gastrointestinal Endoscopy; CBDS, common bile duct stone; CRHS, Chinese Research Hospital Association; CSDE, Chinese Society of Digestive Endoscopology; EASL, European Association for the Study of the Liver; ESGE, European Society of Gastrointestinal Endoscopy; JSGE, Japanese Society of Gastroenterology; NICE, National Institute for Health and Care Excellence; UK, The United Kingdom.

Quality Evaluation of the Guidelines

The quality assessment of the included guidelines using the AGREE II tool yielded the results presented in Table 3. Domain 1 (scope and purpose) obtained an overall score of 77.78% (range 29.17% to 87.50%), Domain 2 (participants involved) obtained an overall score of 45.83% (range 8.33% to 86.11%), and Domain 3 (rigor of development) obtained an overall score of 45.31% (range 18.75% to 80.21%). The median value of Domain 4 (clarity of presentation) was relatively high at 93.06% (range 65.28% to 97.22%). The median value for Domain 5 (applicability) was 59.38% (range 32.29% to 87.50%), and the median value for Domain 6 (editorial independence) was 62.35% (range 2.08% to 83.33%). Finally, an overall recommendation was provided based on the scores. Detailed ratings for each guideline can be found in Table 3. Four guidelines with an overall score greater than 60%^7–9,11 were recommended. The remaining 5 guidelines obtained overall scores between 30% and 60%,^5,6,10,12,13 falling into the category of recommendations that require further improvement. Four evaluators participated in the assessment of the guidelines for choledocholithiasis, and the ICCs of the AGREE II evaluations performed by the evaluators were all greater than 0.8, indicating a high level of consistency in item scores among the evaluators.

TABLE 3.

AGREE II Domain Score and ICC of the Included Guidelines

Guideline	Scope and purpose (%)	Stakeholder involvement (%)	Rigor of development (%)	Clarity and presentation (%)	Applicability (%)	Editorial independence (%)	ICC	Overall assessment (%)
NICE, 20217	29.17	8.33	29.17	93.06	87.50	33.33	0.993	35.07	RM
ESGE, 20198	84.72	52.78	82.29	95.83	62.50	79.17	0.946	75.26	R
ASGE, 20196	87.50	86.11	67.19	93.06	65.63	75.00	0.982	75.91	RM
CRHS, 201912	77.78	27.78	39.06	88.89	54.17	62.50	0.981	55.43	R
CSDE, 201811	84.72	45.83	38.54	83.33	69.79	2.08	0.989	54.08	RM
Williams et al, 20179	77.78	56.94	78.13	81.94	37.50	83.33	0.961	66.41	R
JSGE, 201610	68.06	47.22	54.69	95.83	59.38	68.75	0.984	63.50	R
EASL, 201613	79.17	25.00	45.31	97.22	56.25	56.25	0.987	57.60	RM
NICE, 201414	75.00	43.06	18.75	65.28	32.29	2.08	0.977	35.94	RM
Median score	77.78	45.83	45.31	93.06	59.38	62.50	0.982	57.60	—
Range	29.17-87.50	8.33-86.11	18.75-80.21	65.28-97.22	32.29-87.50	2.08-83.33	0.946-0.989	35.07-75.91

AGREE II indicates Appraisal of Guidelines for Research and Evaluation II; ASGE, American Society for Gastrointestinal Endoscopy; CRHS, Chinese Research Hospital Association; CSDE, Chinese Society of Digestive Endoscopology; EASL, European Association for the Study of the Liver; ESGE, European Society of Gastrointestinal Endoscopy; ICC Intraclass correlation coefficient; JSGE, Japanese Society of Gastroenterology; NICE, National Institute for Health and Care Excellence.

Comparison with Previous Guideline Reviews

In comparison with a previously published guideline review¹⁹ (Table 4), statistically significant differences were observed in 2 domains: Clarity and persistence (P<0.001), and Applicability (P<0.05). This may be attributed to the improved articulation of the purpose and scope during guideline development in recent years, as well as enhanced practical application in clinical practice. However, no significant differences were found in the scores of the 2 guideline reviews regarding the Domains of participants involved, rigor of development, and editorial independence, suggesting that there is still ample room for improvement in current guidelines.

TABLE 4.

Comparison With the Previously Published Guideline Review

Study	Scope and purpose	Stakeholder involvement	Rigor of development	Clarity and presentation	Applicability	Editorial independence	Overall assessment
This study
Mean scores (SD)	73.8 (16.7)	43.7 (20.9)	50.3 (20.6)	88.3 (9.6)	58.3 (15.6)	51.4 (29.8)	57.7 (14.0)
Last study18
Mean scores (SD)	59.6 (18.4)	47.6 (16.3)	52.2 (17.7)	66.5 (8.2)	36.6 (17.3)	49.1 (13.2)	57.0 (19.0)
p	0.81	0.63	0.82	<0.001	0.007	0.81	0.92

This study used the t test to compare these guidelines with previous guideline evaluations regarding scope and purpose, stakeholder involvement, rigor of development, clarity and presentation, applicability, editorial independence, and overall assessment.

Heterogeneity of Recommended Items and Evidence in Choledocholithiasis Guidelines

To further analyze the reasons behind the heterogeneity of the recommendations among different guidelines for choledocholithiasis, we referred to the key recommendation items with relatively high scores in the guideline for diagnosis and treatment⁸ and extracted them. Key recommendations were extracted from the 8 included guidelines (Table 5). Using the guideline⁸ as the reference, we adopted the consistency evaluation tool (measurement scale of rate of agreement)¹⁷ to further analyze the differences and compare the similarities in the key recommendations among different guidelines. If the similarity among recommendations exceeded 60% and if at least 4 guidelines made the same recommendation, the highest evidence supporting the recommendation was extracted and reclassified using the OCEBM grading system (Fig. 2), and then the effect of evidence selection on the strength of the recommendation was found. Two guidelines^7,14 are not included in Fig. 2 due to the absence of references. The main recommendations and supporting evidence for the diagnosis of choledocholithiasis are presented in Table 5.

TABLE 5.

Recommendations for The Diagnosis and Treatment of Choledocholithiasis in the Included Guidelines

	NI7	ES8	AS6	CR12	CS11	We9	JS10	EA13	NI14
Imaging examination
Liver Function	●	●	●	─	●	●	●	●	●
Ultrasound	●	●	●	●	●	●	●	●	●
EUS	●	●	●	●	●	●	●	●	●
MRCP	●	●	●	●	●	●	●	●	●
ERCP	●	●	○	─	○	●	●	─	─
Treatment
ERCP	●	●	●	─	●	●	●	●	●
ERCP+LC	●	●	●	─	●	─	─	●	●
Stone extraction	●	●	─	─	●	●	●	─	●
Biliary drainage	●	●	●	─	●	●	●	●	●
Biliary stent for special situations	─	●	●	─	●	●	●	─	─
EPLBD+EST	─	●	●	─	●	●	●	●	─
Cholecystectomy	●	●	●	─	●	●	─	●	●
Lithotripsy method	─	●	●	●	●	●	─	●	─
Mirizzi	─	─	●	─	─	─	●	─	─

● indicates being recommended definitely; ● indicates being mentioned; ○ indicates not being recommended; ─ indicates not being mentioned.

EPLBD indicates endoscopic papillary large-balloon dilation; ERCP, endoscopic retrograde cholangiopancreatography; EST, endoscopic sphincterotomy; EUS, endoscopic ultrasonography; LC, laparoscopic cholecystectomy; MRCP, magnetic resonance cholangiopancreatography.

FIGURE 2.

Distribution of the highest level of evidence to support similar recommendations for the diagnosis and treatment of choledocholithiasis（2014 to 2021). BD indicates biliary drainage; BT, biliary stent for special situations; CS, cholecystectomy; EE, EPLBD (endoscopic papillary large-balloon dilation)+EST (endoscopic sphincterotomy); EL, ERCP (endoscopic retrograde cholangiopancreatography)+LC (laparoscopic cholecystectomy); ER, ERCP (endoscopic retrograde cholangiopancreatography) used for diagnosis; ER’, ERCP (endoscopic retrograde cholangiopancreatography) used for treatment; EU, EUS (endoscopic ultrasonography); LF, liver function; MR, MRCP (magnetic resonance cholangiopancreatography); SE, stone extraction; ST, cholecystolithotripsy; US, ultrasound.

DISCUSSION

Principal Findings

In this study, we evaluated guidelines for the diagnosis and treatment of choledocholithiasis using the AGREE II tool. The findings revealed a high level of consistency in the recommendations for the diagnosis of choledocholithiasis. However, significant differences were observed in the recommendations pertaining to treatment and preventive management, particularly regarding treatment timing and the appropriate population for ERCP utilization, as well as treatment methods for difficult stone cases. Some recommendations lacked supporting evidence or provided unreasonable citations. Furthermore, the quality of guidelines for the diagnosis and treatment of choledocholithiasis exhibited considerable variation across different guidelines and even within different domains of the same guideline.

Quality Evaluation of the Guidelines by The AGREE II Tool

In the process of scoring using the AGREE II tool, there is a need for a more detailed definition of the “Guideline-appropriate population” in Domain 1. Referring to the description of the population for which the guidelines for other diseases are applicable,^20–22 the guidelines for choledocholithiasis should elaborate on the related factors, such as stone conditions, organ function, and accompanying symptoms. This would ensure accurate application of the recommendations to patients. The overall score of the second domain was relatively low at 46.53%. Several guidelines^6,7,9–14 inadequately describe the information, responsibilities and job duties of those involved in the development, and with the exception of 3 guidelines,^6,7,14 other guidelines primarily considered input from professional medical teams or their stakeholders while neglecting the opinions of patients. Involving patients or other relevant personnel in the guideline development process could enhance the clinical applicability of the guideline and facilitate its improvement in future versions. Concerning the rigor of the 3 guidelines, some guidelines did not use systematic retrieval methods^7,11,12,14 and did not systematically grade the evidence.^7,14 Several guidelines lacked an explanation of the methodology used to formulate the recommendations. Guidelines should detail how the recommendations were developed and the process by which a final decision was made, especially in controversial sections. For a comprehensive analysis of the relationship between the recommendations and supporting evidence, see Table 5.

Only 2 guidelines^8,9 underwent explicit external expert reviews, and 7 guidelines were updates of previous versions.^6–12 However, limited information was provided on how the guidelines were updated. In Domain 4 (clarity and presentation), the median score was 93.06%. The included guidelines generally presented clear and distinct recommendations, with clear and concise main comments.

The median score in Domain 5 was 59.38%, and the low applicability score of the guideline was related to the absence of tools that facilitate guideline practice, such as summary documents, quick reference guides, and training tools. Domain 6 achieved a median score of 62.50%, and the 3 guidelines^7,11,14 did not state that the views or interests of the funding agencies did not have any impact on the formulation of the guidelines. Competing interests are a common source of bias that is easily overlooked, and guideline development committees should consider them to ensure editorial independence.

Analysis of the Reasons for the Heterogeneity of Choledocholithiasis Guideline Recommendations and Evidence

(1) The timing and appropriate populations to receive ERCP for the treatment of choledocholithiasis are quite heterogeneous.

① In the use of ERCP for the treatment of gallstone pancreatitis, the recommended opinion is controversial regarding the timing of early ERCP. The AS guideline⁶ recommends against early ERCP (within 48 h) for patients with gallstone pancreatitis (but not cholangitis or biliary obstruction). The supporting evidence is a meta-analysis²³ that included 5 randomized controlled trials (RCTs) with 644 participants, which concluded that early ERCP should be considered in patients with coexisting cholangitis or biliary obstruction. Another guideline, the We guideline,⁹ suggests that patients with gallstone pancreatitis who do not require ERCP within 72 hours of presentation should consider elective ERCP and endoscopic sphincterotomy,⁸ but this guideline does not provide corresponding supporting evidence. Among the acute pancreatitis guidelines we retrieved,²⁴ the American Gastroenterological Association (AGA) recommends against the routine use of emergency ERCP in patients with acute biliary pancreatitis without cholangitis, although the authors of the guideline, which has limitations, also acknowledged the lack of supporting evidence. The JS guideline¹⁰ recommends timely ERCP for patients with gallstone pancreatitis, and its supporting evidence also uses the meta-analysis adopted by the AS guideline.²³ The CS guideline¹¹ also discusses this issue, and emergency ERCP with endoscopic sphincterotomy (EST) should be performed in patients with acute biliary pancreatitis complicated by acute cholangitis or bile duct obstruction; however, it is controversial whether to perform ERCP if the patient is thought to be severely ill.²⁵ At the same time, each guideline is slightly different for the population to receive ERCP, such as the AS guideline,⁶ which indicates that patients without cholangitis or biliary obstruction should receive ERCP, while the We guideline⁹ targets biliary pancreatitis patients with biliary obstruction or cholangitis; for this recommendation, the supporting evidence in the We guideline⁹ is lacking, and the supporting evidence used in AS guideline⁶ is also of low quality.

② ERCP performed at the same time as cholecystectomy: Most guidelines tend to support the use of “ERCP combined with laparoscopic cholecystectomy” in the treatment of “patients with choledocholithiasis and cholecystolithiasis”,^6–8,11 but the controversy is whether ERCP should be performed at the same time as cholecystectomy. The ES guideline⁸ suggests considering intraoperative rendezvous ERCP in patients with choledocholithiasis undergoing cholecystectomy, and the highest evidence cited is a randomized controlled study²⁶ that included 120 patients and concluded that in cholecystolithiasis patients, the laparoscopic-endoscopic approach may prevent post-ERCP pancreatitis through patient-related risk factors. Another guideline, the NI guideline,⁷ recommends ERCP be performed before or during laparoscopic cholecystectomy. An advantage of performing ERCP preoperatively is that if the choledocholithiasis are not removed, they can be removed again during the next laparoscopic cholecystectomy. However, its relevant supporting evidence is not mentioned in the guidelines. The AS guideline⁶ provides a completely different opinion and suggests that preoperative or postoperative ERCP or laparoscopic treatment be performed for patients at high risk of choledocholithiasis or positive intraoperative cholangiography depending on local surgical and endoscopic expertise. The supporting evidence was 4 RCTs^24,27–29 : (A) A comparison of one-stage surgical laparoscopic cholecystectomy (LC) + laparoscopic common bile duct exploration (LBDE) with 2-stage LC + postoperative ERCP^27,28; (B) A comparison of postoperative ERCP with LC²⁹; and (C) A comparison of patients who underwent cholecystectomy first with those who underwent cholecystectomy after sequential cholangioscopic evaluation.²⁴ None of the above randomized controlled studies considered the simultaneous use of LC+ERCP during surgery, and the relevant supporting evidence cannot strongly explain its recommendation.

The We guideline⁹ recommends transcystic or transductal LBDE as an appropriate technique for choledocholithiasis removal, proposing that surgeons be trained in LBDE to reduce the number of interventions required to manage choledocholithiasis. The guideline compared LBDE with preoperative or postoperative ERCP but not with intraoperative combined ERCP. However, according to the new RCT,³⁰ 104 patients were randomly divided into 2 groups. The patients in the intraoperative ERCP group had a higher biliary clearance rate than those in the LBDE group, and their stone retention rate was lower than that of the patients in the LBDE group, resulting in more efficient stone removal and performance and shorter hospital stays. In a search updated in this study, a meta-analysis³¹ of 8 studies (including 4 RCTs and 4 high-quality non-RCTs) including 2948 patients indicated that intraoperative combined ERCP is more effective in reducing the postoperative stone residual rate.

(2) Most guidelines recommend stone extraction for all patients with choledocholithiasis, whether they are symptomatic or not, given that they are healthy and can tolerate the intervention.^7–11 Most guidelines support limited sphincterotomy combined with endoscopic papillary large-balloon dilation as the first-line approach to remove difficult choledocholithiasis. There are 5 guidelines recommending similar opinions,^6,9–11,13 4 of which were more than 80% consistent, and the similarity among the guidelines¹⁰ and other recommendations was significantly different due to the discussion of the emphasis of the recommendations being placed on the selection criteria for each of the above 2 technologies rather than on the effect of their combined use. EST reduces the need for endoscopic lithotripsy. The incision of the sphincter should be limited, and a larger sphincter incision will bring higher risks, such as bleeding and perforation.⁸ A study of 70 patients compared EST alone with EST+endoscopic papillary large-balloon dilation and concluded that the combination resulted in higher stone clearance and shorter hospital stays and procedures.³² At present, the size of the papillary dilatation balloon is mostly selected in clinical practice according to the degree of bile duct dilatation and the size of choledocholithiasis.

For the treatment of difficult gallstones, similar lithotripsy methods are proposed in various guidelines, but the description of how to choose a method and the applicable circumstances is not detailed and specific, and the evidence support for these lithotripsy methods is absent.^6,8,9,11 Most guidelines recommend that the selection should be based on local experience, economy, technical level, and patient conditions. This study analyzed the abovementioned guidelines for the treatment of difficult stones and combined clinical experience to summarize the corresponding treatment strategies, as shown in Fig. 3.

FIGURE 3.

The treatment strategies of difficult choledocholithiasis.

There are 7 guidelines recommending prophylactic cholecystectomy,^{5,7–9,11,13,14} but they address different situations. The AS, We, and EA guidelines^6,7,9,13,14 discuss cholecystectomy as the most effective measure to prevent recurrence of gallstone pancreatitis when a patient can tolerate it, but the specific operation time is not discussed. The ES guideline⁸ recommends prophylactic cholecystectomy within 2 weeks for patients who undergo ERCP to treat cholelithiasis to avoid gallbladder stones entering the biliary tract after ERCP.

Strengths and Limitations

This study has certain advantages and some limitations. The strengths of this study are as follows: (1) The final score was obtained by multiple investigators together, and appropriate weights were applied to each Domain of the assessment, thus increasing the reliability of the assessment and recommendation of the guidelines; and (2) We evaluated most of the recommendations in the latest guidelines on choledocholithiasis and discussed their heterogeneity. The formulation of relevant recommendations and the use of supporting evidence were analyzed in detail, which is helpful for users to adopt and follow the opinions, as well as for guideline developers to improve the guidelines. The limitations of this study were as follows: (1) In this study, we only evaluated guidelines written in English and Chinese, excluding guidelines published in other languages; and (2) The AGREE II tool can only focus on the approach to guideline development and cannot assess the impact of recommendations on patient clinical outcomes.

CONCLUSIONS

This study highlights the substantial variability in the quality of guidelines for choledocholithiasis, particularly regarding participant involvement, rigor of development, and applicability. There is ample room for improvement in these areas.The recommendations for the diagnosis of biliary calculi showed general consensus across different guidelines, with minimal variations. However, recommendations for treatment vary widely. The timing of ERCP utilization emerged as a major contradiction, with guidelines lacking consensus, and the quality of supporting evidence for relevant recommendations was found to be poor. For patients with choledocholithiasis and gallbladder stones at the same time, there is still a certain gap between the recommendations in the guidelines and clinical practice. In addition, further discussion is needed to establish the indications for prophylactic cholecystectomy. It is essential for guideline developers to address these issues in future updates of choledocholithiasis guidelines, aiming to enhance their clinical applicability.