Comparative efficacy of endoscopic ultrasound-guided biliary drainage versus endoscopic retrograde cholangiopancreatography as first-line palliation in malignant distal biliary obstruction: a systematic review and meta-analysis

Introduction

Approximately 70% of newly diagnosed pancreatic cancers, including pancreatic head adenocarcinoma, cholangiocarcinoma in the lower third of the common bile duct, ampullary carcinoma, or lymph node involvement and metastases, present with some form of biliary obstruction. Biliary decompression is crucial for symptomatic relief, and to facilitate the administration of neoadjuvant or palliative chemotherapy in cases of advanced or inoperable disease [1].

Endoscopic retrograde cholangiopancreatography (ERCP)-guided transpapillary stenting is the recognized first-line palliative treatment for malignant distal biliary obstruction (MDBO). However, ERCP comes with its challenges, including a significant risk of pancreatitis, which has an incidence of up to 3.47% and associated mortality of 3.08%, as well as cholecystitis, cholangitis, stent dysfunction and migration, with a combined incidence rate of 28-36%. Complications are exacerbated by malignant infiltration of the duodenum or papilla, or in cases of surgically modified anatomy that precludes transpapillary stenting [2].

Endoscopic ultrasound-guided biliary drainage (EUS-BD) offers alternative transluminal and transpapillary stenting approaches, including intrahepatic hepaticogastrostomy (EUS-HGS) or extrahepatic choledochoduodenostomy (EUS-CDS), and rendezvous (EUS-RV) techniques [3]. Initially introduced by Giovannini et al in 2001 using plastic stents, the evolution to self-expandable metal stents was marred by complications including cholangitis, biliary peritonitis, and duodenal perforation. The introduction of lumen-apposing metal stents, and more recently electrocautery-enhanced lumen-apposing metal stents (Hot AXIOS or AXIOS-EC™, Boston Scientific Marlborough, MA, USA), has simplified EUS-CDS techniques, enabling a free-hand, single-step, and exchange-free procedure that reduces operative time and theoretically minimizes the risk of bile leak and peritonitis [4-6].

Through several randomized controlled trials (RCTs) and meta-analyses, EUS-BD has established itself as a viable second-line option in the management of MDBO when ERCP fails [7,8]. Despite its successes, the evidence supporting the use of EUS-BD as a primary treatment option for MDBO remains limited. This systematic review and meta-analysis aimed to assess and compare the efficacy of EUS-BD and ERCP in the initial palliative management of MDBO, potentially redefining treatment paradigms based on efficacy, safety, and procedural outcomes.

Materials and methods

Results

Primary outcomes

Technical success

The meta-analysis suggested a possible higher technical success rate for EUS-BD over ERCP (Fig. 2), with a common effects model (CEM) odds ratio (OR) of 1.77 (95% confidence interval [CI] 1.00-3.14) and a random effects model (REM) OR of 1.37 (95%CI 0.51-3.70). However, wide confidence intervals encompassing 1 imply substantial uncertainty. The influence of individual studies varied; notable was the study by Dhir et al [18], which heavily weighted (36.8% in the CEM and 24.6% in the REM) and impacted the overall result. Variability in the studies was moderate (I²=49%, P=0.08), suggesting that differences were not merely due to chance, yet not significant enough to discredit the pooled estimate.

Figure 1 The preferred reporting items for systematic reviews and meta-analyses (PRISMA) 2020 flow diagram of included studies

ERCP, endoscopic retrograde cholangiopancreatography

Figure 2 Forest plot comparing technical success

EUS-BD, endoscopic ultrasound-guided biliary drainage; ERCP, endoscopic retrograde cholangiopancreatography; OR, odds ratio; CI, confidence interval

Table 1 Comprehensive overview of baseline demographics

Clinical success

The analysis indicated no significant difference in clinical success rates, with a CEM OR of 0.79 (95%CI 0.43-1.43) and an REM OR of 0.80 (95%CI 0.43-1.47) (Fig. 3). The confidence intervals spanning 1 reflect substantial uncertainty. Notably, the study by Dhir et al [18], held the greatest weight (41.5% in CEM and 43.7% in REM), significantly influencing the meta-analysis. The studies exhibited negligible heterogeneity (I²=0%, P=0.82), suggesting that any differences in outcomes were consistent with chance. For a detailed analysis of publication bias of primary outcomes, see Supplementary Fig. 3 and 4.

Figure 3 Forest plot comparing clinical success

EUS-BD, endoscopic ultrasound-guided biliary drainage; ERCP, endoscopic retrograde cholangiopancreatography; OR, odds ratio; CI, confidence interval

Secondary outcomes

Adverse events

This plot compared the rates of adverse events between EUS-BD and ERCP (Fig. 4). The CEM showed an OR of 0.80 (95%CI 0.53-1.20), while the REM had a very similar OR of 0.81 (95%CI 0.51-1.27). Both confidence intervals cross the null value, suggesting that there was no statistically significant difference in adverse event rates between the 2 procedures. The heterogeneity was low (I²=21%, P=0.28), indicating that there was little variability among the study results, and they were fairly consistent.

Figure 4 Forest plot comparing adverse events

EUS-BD, endoscopic ultrasound-guided biliary drainage; ERCP, endoscopic retrograde cholangiopancreatography; OR, odds ratio; CI, confidence interval

Adverse events – pancreatitis

This analysis assessed the occurrence of pancreatitis following EUS-BD vs. ERCP (Fig. 5). The CEM indicated an OR of 0.09 (95%CI 0.02-0.34), demonstrating a significantly lower rate of pancreatitis with EUS-BD. The REM was consistent, with an OR of 0.10 (95%CI 0.03-0.39). These results are statistically significant and suggest a strong protective effect of EUS-BD against pancreatitis compared to ERCP. The heterogeneity among studies was nonexistent (I²=0%, P=0.94), pointing to a consistent effect across different studies.

Figure 5 Forest plot comparing incidence of pancreatitis as an adverse event

EUS-BD, endoscopic ultrasound-guided biliary drainage; ERCP, endoscopic retrograde cholangiopancreatography; OR, odds ratio; CI, confidence interval

Procedural time

The forest plot analyzing mean times indicated no substantial difference between EUS-BD and ERCP, as reflected by a CEM OR of 1.53 (95%CI 0.97-2.42) and a REM OR of 1.52 (95%CI 0.96-2.40). Both confidence intervals are close to the null value and overlap it, implying significant uncertainty. The studies included showed minimal heterogeneity (I²=0%, P=0.49), suggesting that the variation in outcomes was probably due to chance.

The forest plot focusing on median times suggests EUS-BD is associated with lower odds compared to ERCP, CEM OR of 0.54 (95%CI 0.32-0.92), indicating statistical significance. The REM showed an OR of 0.59 (95%CI 0.19-1.86), but with a wide CI that included 1, indicating uncertainty. There was significant heterogeneity among the studies (I²=75%, P=0.02), which suggests that the variability in outcomes is more than would be expected by chance and may impact the reliability of the pooled estimate. For a detailed analysis of procedural times, see Supplementary Fig. 5,6.

Duration of hospital stay

The forest plot examining hospital stay durations compared EUS-BD and ERCP with a CEM OR of 0.84 (95%CI 0.31-2.25) and an identical REM OR at 0.84 (95%CI 0.31-2.25). The confidence intervals are wide and include 1, suggesting no clear difference between the procedures regarding the length of hospital stay. The heterogeneity across the included studies was negligible (I²=0%, P=0.80), indicating a consistent effect size across studies. For a detailed analysis of the duration of hospital stay, see Supplementary Fig. 7.

30-day mortality

The plot presents data on 30-day mortality for EUS-BD vs. ERCP, showing a CEM OR of 0.62 (95%CI 0.17-2.30), with the same OR for the REM. The confidence interval is wide and crosses the null value, indicating no statistically significant difference between the 2 procedures in terms of mortality at 30 days. There was no reported heterogeneity (I²=NA), implying consistent findings across the studies included. For a detailed analysis of 30-day mortality, see Supplementary Fig. 8.

Reintervention rates

This analysis compared reintervention rates between EUS-BD and ERCP. The CEM showed an OR of 0.58 (95%CI 0.36-0.92), indicating a statistically significant result that suggests lower reintervention rates for EUS-BD. The REM OR was 0.64 (95%CI 0.33-1.24), which includes 1 within the confidence interval, pointing to a lack of statistical significance and greater uncertainty. There was moderate heterogeneity (I²=34%, P=0.18), suggesting that the differences in reintervention rates observed may not be entirely attributable to chance, but also not significant enough to suggest inconsistency across studies. For a detailed analysis of re-intervention rates, see Supplementary Fig. 9.

Discussion

This systematic review and meta-analysis provide a comprehensive comparison of the efficacy of EUS-BD vs. ERCP in the primary palliation of MDBO. Regarding primary procedural outcomes, the higher technical success rate observed for EUS-BD in our analysis aligns with previous studies, indicating its potential as a viable alternative to ERCP, especially in complex cases where ERCP is deemed technically challenging. These cases often involve altered surgical anatomy or malignant infiltration obstructing the duodenal papilla, conditions under which EUS-BD has shown superior adaptability [20]. A recent meta-analysis of 7887 patients, including 155 studies, showed that clinical outcomes are best (8.8% total adverse events) when biliary drainage is conducted using the natural orifice or major duodenal papilla via EUS-RV [21]. Nevertheless, the wide confidence intervals in our results reflect significant variability among studies, suggesting that while EUS-BD has promise, its performance is highly dependent on specific patient and clinical conditions.

Clinical success rates were comparable between EUS-BD and ERCP, indicating that both techniques are effective for symptom relief when they are technically successful. Secondary outcomes, including procedural time, duration of hospital stay, 30-day mortality and reinterventions, were not statistically significant, though some of them showed trends but with significant heterogeneity. In a patient-centered care approach, with the above similarity of outcomes between these 2 procedures, selection of a technique should be customized to the patient’s specific clinical situation, adverse events and cost effectiveness, without sacrificing palliative outcomes.

In our study, a critical advantage of EUS-BD over ERCP was its association with a lower risk of pancreatitis, which is a major concern with ERCP, and contributes significantly to healthcare costs—over $200 million annually in the U.S. alone—as well as being a primary cause of litigation related to ERCP procedures. According to a meta-analysis of 89 RCTs, the risk profile for pancreatitis included precut sphincterotomy, pancreatic sphincterotomy, difficult cannulation, pancreatic duct injection, and sphincter of Oddi dysfunction [22] Notably, our results demonstrate a significantly lower incidence of pancreatitis with EUS-BD compared to ERCP, echoing previous findings that EUS-BD may offer a safer profile, with a reported cumulative total adverse event rate of 17% [6,23].

As a second line approach after failed ERCP, the economic benefit extends beyond the initial procedure costs, as despite EUS-BD having higher initial charges, it generally incurs lower overall expenses, with fewer reinterventions compared to percutaneous transhepatic biliary drainage, as demonstrated in cost-effectiveness analyses [24,25]. The significantly lower incidence of pancreatitis with EUS-BD not only highlights its clinical safety, but also promises substantial theoretical economic advantages, despite the lack of any direct head-to-head comparisons with ERCP.

The adoption of EUS-BD in healthcare systems is shaped by factors including the availability of specialized technology and expert endoscopists. This confines its use to well-resourced tertiary care centers [26]. However, it has been shown that the advanced training required for EUS is easier to master compared to ERCP, with 82% of fellows achieving technical competence in EUS procedures after a 1-year endoscopy fellowship, compared to 60% with ERCP procedures [27]. The cost of equipment and the need for specialized training create barriers to the widespread adoption of EUS methods, but also represent areas where targeted investments can facilitate broader use.

Despite these promising findings, our study is not without limitations. The heterogeneity in some of the analyzed outcomes suggests varying study designs, methodologies and patient populations, which could influence the generalizability of the results. Additionally, the moderate heterogeneity observed in the reintervention rates indicates that other factors, possibly related to the procedural expertise or healthcare setting, might impact these outcomes.

In conclusion, while our analysis supports the use of EUS-BD as an effective alternative to ERCP, especially in reducing the risk of pancreatitis and potentially lowering reintervention rates, both techniques remain valuable tools in the management of MDBO. Future research should focus on performing randomized control trials or head-to-head comparisons to evaluate long-term outcomes, patient-reported quality of life measures, and cost-effectiveness analyses to further delineate their roles in clinical practice. As the field advances, it will be crucial for ongoing updates to clinical guidelines to incorporate new evidence, ensuring optimal patient outcomes through informed, evidence-based decision-making.