INTRODUCTION
ERCP with transpapillary stent placement is the first line of treatment to achieve biliary drainage (BD) in patients with malignant or benign biliary obstruction. Sometimes, ERCP is not possible due to reasons such as surgically altered anatomy (SAA) or gastric outlet obstruction.[1] EUS-guided BD (EUS-BD) is an effective alternative in cases of failed ERCP and has potential advantages over percutaneous transhepatic BD such as providing internal BD, which is more physiologic, and avoidance of an external catheter.[2-5] One meta-analysis evaluating the efficacy and safety of EUS-BD found that the rates of clinical success and adverse events were 87% and 18%, respectively.[6]
EUS-BD has been found to be a safe and effective method of providing BD in patients with benign as well as malignant biliary obstruction and also in patients with normal or SAA.[7,8] Traditionally, EUS-BD has mostly been used in patients with malignant biliary obstruction after failed ERCP or if ERCP is not technically possible.[9,10] Recently, several studies have shown that EUS-BD is also safe and effective in patients with benign biliary obstruction.[11,12] Previous meta-analyses evaluating the efficacy and safety of EUS-BD have largely focused on patients with malignant biliary obstruction.[6,13,14] To date, no meta-analysis has evaluated the role of EUS-BD in benign biliary obstruction. As such, we performed a meta-analysis to evaluate the efficacy and safety of EUS-BD in the management of benign biliary obstruction.
METHODS
Data sources and search strategy
We followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) to conduct this meta-analysis. An experienced medical librarian (W. L-S.) performed a comprehensive search of MEDLINE (PubMed platform, NCBI), EMBASE (Embase.com, Elsevier), Web of Science Core Collection (Clarivate), and the Cochrane Central Register of Controlled Trials (Cochrane Library, Wiley) from inception to July 8, 2022. There was no restriction on language in conducting the search. The search included truncation-expanded keywords and database-specific subject terms for benign biliary diseases and EUS-guided BD. Full search strategies from all databases are provided in Supplementary Table 1. Two authors (F. K. and S. S.) independently reviewed the titles and abstracts of the retrieved articles and excluded those that did not provide data on our outcomes of interest. Full texts of the remaining articles were reviewed. We also reviewed the references of these articles to identify any additional study with relevant information. The screening results are illustrated in the form of a PRISMA flowchart in Figure 1.
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SUPPLEMENTARY TABLE 1: FULL SEARCH STRATEGIES (ALL SEARCHED PERFORMED AUGUST 12, 2021)
Figure 1: PRISMA flowchart. PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses
Inclusion and exclusion criteria
Two authors (F. K. and M. A. K.) independently reviewed original studies based on the preestablished inclusion criteria that are detailed below. We only included studies that evaluated the efficacy and safety of EUS-guided BD in the management of benign biliary obstruction. We included peer-reviewed publications that comprised patients with normal anatomy as well as SAA which underwent any form of EUS-guided BD method such as hepaticoenterostomy, choledochoenterostomy, and rendezvous procedure. We excluded case reports, case series with fewer than five patients, and abstracts. We also excluded studies that included patients with benign as well as malignant biliary obstruction but did not separately report data on outcomes of interest for these patients. If there were multiple publications from the same cohort, we included only the most recent publication and/or the publication with more information. All articles were downloaded into EndNote X9 (Clarivate, Philadelphia, Pennsylvania, USA), a bibliographic database manager. Duplicate citations were removed using successive EndNote algorithms based on bibliographic information and subsequent visual inspection.
Data extraction
Two authors (F. K. and M. A. K.) independently assessed the eligibility of included studies and collected data using data extraction forms that were specifically designed for this study. Any disagreement between individual authors was resolved by a repeat review of data and discussion with a third reviewer (D. G. A.). Extracted data included year of publication, number of patients with normal anatomy versus SAA, indications for BD, technical success, clinical success, adverse events, method of BD, and types of stents used. These data are summarized in Table 1. The methods of BD included hepaticogastrostomy (placement of stent between stomach and intrahepatic bile duct), hepaticojejunostomy (placement of stent between jejunum and intrahepatic bile duct), choledochojejunostomy (placement of stent between jejunum and common bile duct), and EUS rendezvous (bile duct is accessed through EUS and then wire is advanced into bile duct through major papilla into duodenum. Alongside wire, a duodenoscope is advanced to the major papilla. The biliary tree is then cannulated with a sphincterotome using the guidewire placed via EUS as a guide and then ERCP is completed) and choledochoduodenostomy (placement of stent between duodenum and bile duct) and EUS-guided methylene blue injection for identification of the major papilla.
Table 1: Characteristics of studies
Quality assessment
We assessed the quality of studies using the Methodological Index for Nonrandomized Studies (MINORS) criteria.[15] Noncomparative studies are scored on 8 items and comparative studies are scored on 12 items of MINORS criteria. Each item is scored from 0 to 2 (0 if not reported, 1 when reported but inadequate, and 2 when reported and adequate). Therefore, the ideal global score for noncomparative studies is 16. The quality of studies was classified as poor (score ≤5), fair (score 6–10), or high quality (≥11), as described previously.[16,17] Two authors (U. F. and Z. E.) independently performed the quality assessment, and any disagreement was discussed with a third reviewer (F. K.). The quality assessment of studies is summarized in Supplementary Table 2.
Supplementary Table 2: Methodological index for nonrandomized studies score for methodological quality assessment of included studies
Data synthesis and statistical analysis
Our primary outcome of interest was the rate of technical success of EUS-guided BD among patients with benign biliary obstruction. The secondary outcomes were the rates of clinical success and adverse events. Subgroup analyses were performed including patients with normal anatomy versus SAA. As not all studies reported both technical and clinical success, which could lead to the impression that pooled clinical success was higher than pooled technical success, we performed a sensitivity analysis for technical success including studies that reported both technical and clinical success to address this concern. We calculated pooled rates with 95% confidence intervals (CIs) for outcomes of interest, and data were transformed using logit transformations. We assessed heterogeneity by I2 statistics. P < 0.1 for Cochran’s Q-test or an I2 value > 50% indicated significant heterogeneity. We assessed publication bias by using funnel plots and Egger’s test for the outcomes including 10 or more studies. If publication bias was detected, the effect size was recalculated using Duval and Tweedie’s “trim-and-fill” test based on the linear model. The statistical analysis was performed using comprehensive meta-analysis software.
RESULTS
The search strategy produced 302 articles, 90 of which were removed after being identified as duplicates [Figure 1]. From the remaining 212 articles, 192 were removed after title and abstract review. Two additional relevant articles were identified from review of bibliographies. Full texts of these 22 articles were reviewed. One case report and one case series with fewer than five patients were ultimately excluded. Four studies were excluded because these did not separate data between patients with benign or malignant biliary obstruction. Two studies with overlapping data were excluded.
Overall, 14 studies with 329 patients were included in the final analysis.[11,12,18-29] One hundred and ninety-three patients had SAA and 136 patients had normal anatomy. Among the studies that reported numerical data with regard to the selected method for BD, 56% underwent hepaticogastrostomy, 6% hepaticojejunostomy, 2% choledochojejunostomy, 29% EUS rendezvous, 1% choledochoduodenostomy, 1% hepaticoduodenostomy, and 4% underwent EUS-guided methylene blue injection for identification of the major papilla.
Technical success
The pooled rate (95% CI) of technical success was 88% (83%, 92%), I2 = 10% [Figure 2]. Egger’s test showed no publication bias (P = 0.07). On subgroup analysis including patients with SAA, the rate (95% CI) of technical success was 92% (85%, 96%), I2 = 0% [Supplementary Figure 1a]. When we performed a subgroup analysis of patients with normal anatomy, the rate (95% CI) of technical success was 83% (75%, 89%), I2 = 0% [Supplementary Figure 1b]. On sensitivity analysis including studies that reported both technical and clinical success, the pooled rate (95% CI) of technical success was 92% (88%, 95%) [Supplementary Figure 2].
Figure 2: Rate of technical success of EUS-guided biliary drainage for benign biliary obstruction. CI: Confidence interval
Supplementary Figure 1: (a) Rate of technical success of EUS-guided biliary drainage for benign biliary obstruction with SAA. (b) Rate of technical success of EUS-guided biliary drainage for benign biliary obstruction with normal anatomy. SAA: Surgically altered anatomy, CI: Confidence interval
Supplementary Figure 2: Rate of technical success of EUS-guided biliary drainage for benign biliary obstruction only including studies that reported both technical and clinical success. CI: Confidence interval
Clinical success
The pooled rate (95% CI) of clinical success was 89% (83%, 93%), I2 = 0% [Figure 3]. On subgroup analysis including patients with SAA, the rate (95% CI) of clinical success was 89% (75%, 96%), I2 = 25% [Supplementary Figure 3a]. When we performed a subgroup analysis including patients with normal anatomy, the rate (95% CI) of clinical success was 91% (66%, 98%), I2 = 0% [Supplementary Figure 3b].
Figure 3: Rate of clinical success of EUS-guided biliary drainage for benign biliary obstruction. CI: Confidence interval
Supplementary Figure 3: (a) Rate of clinical success of EUS-guided biliary drainage for benign biliary obstruction with SAA. (b) Rate of clinical success of EUS-guided biliary drainage for benign biliary obstruction with normal anatomy. SAA: Surgically altered anatomy, CI: Confidence interval
Adverse events
The pooled rate (95% CI) of adverse events was 19% (13%, 26%), I2 = 36% [Figure 4]. Egger’s test did not detect publication bias (P = 0.45). On subgroup analysis including patients with SAA, the rate (95% CI) of adverse events was 22% (9%, 43%), I2 = 63% [Supplementary Figure 4a]. When we performed a subgroup analysis including patients with normal anatomy, the rate (95% CI) of adverse events was 21% (14%, 31%), I2 = 0% [Supplementary Figure 4b].
Figure 4: Rate of adverse events of EUS-guided biliary drainage for benign biliary obstruction. CI: Confidence interval
Supplementary Figure 4: (a) Rate of adverse events of EUS-guided biliary drainage for benign biliary obstruction with SAA. (b) Rate of adverse events of EUS-guided biliary drainage for benign biliary obstruction with normal anatomy. SAA: Surgically altered anatomy, CI: Confidence interval
DISCUSSION
Our meta-analysis demonstrates that EUS-BD is a safe and effective option in patients with benign biliary obstruction. ERCP is the gold standard treatment for biliary obstruction, and the use of EUS-BD is typically reserved for patients who have failed ERCP or where ERCP is technically not possible. Several meta-analyses have demonstrated the efficacy and safety of EUS-BD in the management of malignant biliary obstruction.[6,13,14] Our meta-analysis supports the use of EUS-BD to achieve BD in patients with benign biliary obstruction as well. In our study, we found that the rate of technical success was 87% (81%, 92%), which is comparable to the reported technical success of EUS-BD for malignant biliary obstruction.[5,6]
ERCP in patients with SAA can be challenging. We found that the rate of technical success of EUS-BD in cases of SAA was 92% (85%, 96%), far better than that seen when attempting ERCP in patients with SAA with a single-balloon enteroscope (SBE). One can argue for using EUS-BD as a first-line treatment to achieve BD in SAA cases given its high success rate and substantially shorter procedure time compared to SBE-assisted ERCP. However, the rate of adverse events with SBE-assisted ERCP is lower compared to EUS-BD. In a meta-analysis including 15 studies, Inamdar et al. showed that the rate of adverse events with SBE-assisted ERCP was 6.5%.[30] We found that the rate of adverse events of EUS-BD for SAA was 22% (9%, 43%).
In patients with normal anatomy and benign biliary obstruction, ERCP sometimes cannot be performed due to reasons such as inability to identify papilla, failed cannulation, and benign gastric outlet obstruction by conditions such as pancreatic walled-off necrosis or peptic ulcer disease. EUS offers a variety of options in these cases to achieve BD including EUS-guided rendezvous, hepaticogastrostomy, choledochoduodenostomy, and EUS-guided methylene blue injection for identification of papilla. We found that the rate of technical success of EUS BD in patients with normal anatomy was high at 83% (75%, 89%). However, the rate of adverse events was also high at 21% (14%, 31%), suggesting the need for ongoing selection, in most patients, after attempts at ERCP as first-line treatment for benign biliary obstruction.
Methods of BD varied across the studies included in our meta-analysis. Hepaticogastrostomy was the most commonly used method and EUS rendezvous was the second most commonly used method of BD. Hepaticogastrostomy and hepaticojejunostomy are useful in patients with SAA.[31] These can be technically challenging in patients with benign biliary obstruction because biliary system is nondilated. Furthermore, these methods offer one advantage over EUS rendezvous by avoiding the risk of pancreatitis. The potential complications of hepaticogastrostomy and hepaticojejunostomy include bile peritonitis, pneumoperitoneum, bleeding, and stent dislodgement.[31] EUS rendezvous represents a method of natural BD in patients with normal anatomy with benign biliary obstruction. Like any ERCP procedure, there is a risk of pancreatitis associated with ERCP after EUS rendezvous.
This is the first systematic review and meta-analysis to evaluate the efficacy and safety of EUS-BD for benign biliary obstruction. Our comprehensive literature search identified a large number of relevant studies to evaluate the usefulness of EUS-BD in patients with SAA as well as normal anatomy. We found low heterogeneity in most of the analyses. More than half of the studies included in our meta-analysis were rated as of fair quality based on MINORS criteria [Supplementary Table 2]. Our meta-analysis has several limitations. All of the included studies were observational which have intrinsic shortcomings with risks of measured and unmeasured confounding. We found evidence of clinical heterogeneity across studies. Types of stents (metal versus plastic) used varied across the studies [Table 1]. The methods to achieve EUS-BD such as hepaticoenterostomy, choledochoenterostomy, and EUS rendezvous also varied across the studies. As numerical data were not consistently reported for each of these techniques, we could not perform subgroup analyses based on the methods of BD.
CONCLUSION
Our meta-analysis demonstrated that EUS-BD is an effective and safe approach in patients with benign biliary obstruction and should be considered after a failed attempt at ERCP or when ERCP is not technically possible.
Supplemental material
Supplementary information is linked to the online version of the paper on the Endoscopic Ultrasound website.
Financial support and sponsorship
Nil.
Conflicts of interest
Douglas G. Adler is a Co-Editor in Chief of the journal. This article was subject to the journal’s standard procedures, with peer review handled independently of the editor and his research group.
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