Introduction

The first line treatment for biliary obstruction is endoscopic retrograde cholangiopancreatography (ERCP). However, in some situations such as duodenal obstruction or hilar obstruction or surgically altered anatomy, conventional endoscopic management fail. Hepaticogastristomy drainage (HGS) through endoscopic ultrasound has emerged as a new technique for biliary decompression in case of ERCP failure. We hereby aim to evaluate long-term efficacy of EUS-HGS.

Aims & Methods

One hundred ninety-eight patients undergoing EUS-HGS using long partially covered metallic stent in 3 academic centers from January 2010 to January 2022 were retrospectively studied . Technical and functional success, adverse events, recurrent biliary obstruction (RBO), and reinterventions were evaluated.

Results

The principal cause of malignant biliary obstruction was pancreatic cancer in 47,6 %. Patients were metastatic at the time of HGS in 65,2% of cases. Patients were male in 53,8% with mean bilirubin of 58.74 mg/dL. The main reason for HGS was duodenal obstruction (30,9%) followed by failed biliary cannulation (30,4%). The median overall survival rate was 3.1 months [IC 95%; 2.2 - 3.97]. In the entire cohort 35 patients / 198 had recurrent biliary obstruction (17,7%) with median stent patency of 448 days. On multivariate analysis, age was associated with lower chance of stent dysfunction (HR = 0.97 [0.95-0.99], p=0.028). Stent type, stent diameter, stent size, size of puncture, ascites and cause of malignant obstruction were not associated with stent patency. Reintervention through the EUS-HGS route was technically possible in most cases.

Conclusion

EUS-HGS using for unresectable malignant biliary obstruction was safe and effective on the long term with low rate of stent dysfunction and recurrent biliary obstruction . Patient's prognosis was primarily determined by the underlying disease.

Introduction

EUS-guided hepaticogastrostomy (EUS-HGS) is a novel technique that allows internal drainage of the biliary system via the stomach. This approach may be of value in patients with duodenal obstruction, surgically altered anatomy, or in hilar strictures with inadequate drainage of the left hepatic duct by other techniques (1, 2). However, this procedure has a high technical complexity and until recently no dedicated stents were available exposing the patient to adverse events such as the risk of biliary leakage and stent migration (3). A partially covered self-expanding metallic stent (pcSEMS) with anti-migration flaps may overcome these risks. So far, the available data on the use of this specific stent is limited, and prospective studies are particularly missing.

Aims & Methods

Aim of this study was to assess the safety and feasibility of EUS-HGS in patients with an inoperable malignant biliary obstruction, with the use of this dedicated stent. This prospective single-center study included patients with inoperable malignant biliary obstruction that underwent an EUS-HGS. Patients were ineligible in case of uncontrolled coagulopathy, tumor infiltration in the gastric wall, intervening blood vessels or extensive amount of ascites. Procedure was performed with a 10cmx10mm pcSEMS (Giobor stent, Taewoong Medical). Primary outcome was safety, defined as rate of procedural related adverse events (AEs) and mortality <30 days. Technical and clinical success rate were evaluated as secondary endpoints, defined as successful deployment of the stent in the intended location and at least 50% decrease of bilirubin <14 days.

Results

Between January 2022 and July 2024, 25 patients (14 female [56%], median age 70 years [IQR 64-76]) were included. Reason to perform EUS-HGS included duodenal obstruction (n=12), altered anatomy (n=6) or failed drainage of the left hepatic duct by ERCP (n=7). In 21/25 patients EUS-HGS was technically successful (84%). In one patient the procedure was aborted due to a self-limiting bleeding after puncture of the bile duct, in one patient due to unsuccessful cannulation of the central bile duct and in two patients the cholangiogram showed previously unidentified intrahepatic strictures that precluded adequate drainage by EUS-HGS. No severe periprocedural AEs occurred. Three patients (14%) were re-admitted with presumed cholangitis <30 days after the procedure; two with undrained right-sided bile ducts for which a percutaneous drain was placed, and one patient due to obstruction of the bile duct branches by the covered part of the stent, for which an endoscopic re-intervention was performed replacing the Giobor stent by a fully covered and uncovered SEMS. Five patients died within 30 days due to fulminant disease progression. None of these patients experienced procedural related AEs. Clinical success was achieved in 18/19 (95%) patients with technical success and follow-up of at least two weeks. Six out of the 18 patients with clinical success developed recurrent biliary obstruction after a mean of 105 days (SD 80). Obstruction was caused by hyperplasia at the uncovered portion of the stent (n=3) and due to sludge obstructing the stent (n=3). Successful re-intervention was performed in all patients.

Conclusion

This prospective study shows that EUS-HGS with a dedicated partially covered stent is feasible and safe. Tissue hyperplasia in the uncovered part of the stent and sludge obstruction may compromise long-term stent patency. Larger, comparative studies addressing stent design and timing of EUS-HGS are eagerly awaited.

References

1. Pawa, S., et al., American Society for Gastrointestinal Endoscopy guideline on the role of therapeutic EUS in the management of biliary tract disorders: summary and recommendations. Gastrointest Endosc, 2024.
2. van der Merwe, S.W., et al., Therapeutic endoscopic ultrasound: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy, 2022. 54(2): p. 185-205.
3. Binda, C., et al., Efficacy and safety of endoscopic ultrasound-guided hepaticogastrostomy: a meta-regression analysis. Endoscopy, 2024. 56(9): p. 694-705

Introduction

With accumulating evidence on endoscopic ultrasonography-guided hepaticogastrostomy (EUS‑HGS) as a salvage treatment for malignant biliary obstruction (MBO), EUS-HGS has now recognized as one of the primary options even in patients with possible ERCP. However, recurrent biliary obstruction (RBO) occasionally occurs after EUS-HGS and it might impose a heavy burden on patients.

Aims & Methods

This study aimed to investigate the safety and effectiveness of reintervention for RBO after EUS-HGS.
Between August 2011 and February 2023, 177 patients with MBO underwent EUS-HGS using self-expandable metal stent (SEMS), and among them a total of 45 patients who required reintervention for RBO after EUS-HGS were enrolled in this study. Technical success (defined as successful reintervention through the HGS stent), clinical success (defined as successful management of cholangitis and/or a 50% decrease or normalization of the bilirubin level within 14 days after any reintervention), adverse events (AEs), time to RBO (TRBO) and overall survival (OS) were investigated. Potential factors associated with technical success were also explored.

Results

MBO was located at distal in 26 (57.8%) and at proximal in 19 (42.2%), with major underlying disease of biliary tract cancer (n = 21, 46.7%) and pancreatic cancer (n = 18, 40.0%). Five patients with proximal MBO underwent EUS-HGS combined with bridging stenting across the hepatic hilum, while all of the remaining had EUS-HGS alone. Median time to reintervention after EUS-HGS was 80 days (95% CI, 62-131 days) and the major causes of reintervention were hyperplasia at uncover portion of the EUS-HGS stent (n = 24, 53.3%) followed by food impaction or sludge formation (n = 8, 17.8%), stent migration (n = 5, 11.1%) and additional biliary obstruction (n = 4, 8.9%). Technical success was achieved in 39 (88.9%). In 6 cases with technical failure, salvage procedures including ERCP (n = 3), PTBD (n = 2) and additional HGS (n = 1) were performed, which eventually resulted in clinical success in 43 patients (95.5%). Although a mild transit fever was developed in one patient, no severe AEs or procedure-related deaths were observed. Median TRBO and OS after reintervention were 168 days and 161 days, respectively. Notably, patients with distal MBO had a longer TRBO while a shorter OS as compared to those with proximal MBO (median TRBO of 168 days vs. 118 days, p = 0.041 and median OS of 113 days vs. 345 days, p = 0.025). Proximal MBO was associated with technical failure of reintervention in multivariable analysis (odds ratio of 7.26, 95% confidence interval, 0.18-0.98, p = 0.046).

Conclusion

Reintervention for RBO after EUS‑HGS was technically feasible and clinically effective, without any severe AEs, especially in patients with distal MBO.

Introduction

Endoscopic retrograde cholangiopancreatography (ERCP) in patients with malignant distal biliary obstruction (MBO) is associated with a 75-94% technical success rate and up to 3-18% pancreatitis rate.(1-5) Endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) potentially results in higher technical success without the risk of pancreatitis. However, currently available prospective studies regarding EUS-CDS instead of ERCP used self-expandable metal stents (SEMS), while single step lumen-apposing metal stents (LAMS) may simplify the procedure and improve outcome.

Aims & Methods

Aim of this single-centre prospective pilot study was to assess the effectiveness and safety of EUS-CDS using LAMS as primary drainage strategy in MBO. Patients with a proven MBO and bile duct diameter of at least 12mm who required biliary drainage were included, excluding patients with gastric outlet obstruction. Patients underwent EUS-CDS using a 6x8mm LAMS. Primary outcome was technical success confirmed by a cholangiogram. Secondary outcomes were clinical success, defined as 50% decrease of bilirubin or relieve of symptoms after technical success without re-intervention, procedure time, adverse events (AEs) and re-interventions within 6 months.

Results

Overall, 22 patients were enrolled (median age 69.5 years [IQR 64-75.25], 7 male [32%]). The majority was diagnosed with pancreatic ductal adenocarcinoma (n=20, 91%). All tumor stages were included (10 resectable, 6 locally advanced, 6 metastatic). Patients had a median bile duct diameter of 16 mm (IQR 13-20) and median bilirubin level of 225 µmol/L (IQR 130.75-335.25) prior to the intervention.
Technical success was achieved in 20/22 patients (91%). In one patient the stent was unintentionally placed in the cystic duct requiring a successful second EUS-CDS procedure. In the second patient the stent was maldeployed in the bile duct wall and ERCP was performed in the same procedure. Median procedure time was 11 minutes (IQR 7-16). Clinical success was achieved in 18/20 patients (90%). In the 2 remaining patients adequate biliary drainage was later achieved after additional placement of a double pigtail stent (DPS) through the LAMS.
Except for the described endoscopically treated perforation, no periprocedural adverse events occurred. Eight patients (36%) experienced a possible related adverse event within 30 days after stent placement. Six patients developed cholangitis which was considered stent dysfunction. One patient had mild intermittent abdominal pain which resolved after placement of a DPS through the LAMS and one patient developed rhabdomyolysis and kidney failure of unknown relation to the procedure which completely resolved. One patient died within 30 days due to fulminant disease progression which was considered unlikely related to the procedure.
Eleven patients (55%) experienced stent dysfunction within 6 months, presenting with either cholangitis (n=10) or jaundice (n=1). In 2 patients cholangitis was sufficiently treated with antibiotics while 9 patients needed a re-intervention.

Conclusion

The present study supports the safety and feasibility of EUS-CDS using LAMS as the primary drainage strategy in patients with MBO. However, the high incidence of stent dysfunction currently limits the use of EUS-CDS with LAMS solely as a valid alternative to ERCP with SEMS.

References

1. Bang et al. Stent placement by EUS or ERCP for primary biliary decompression in pancreatic cancer: a randomized trial (with videos). Gastrointest Endosc. 2018 Jul;88(1):9-17.
2. Paik et al. EUS-Guided Biliary Drainage Versus ERCP for the Primary Palliation of Malignant Biliary Obstruction: A Multicenter Randomized Clinical Trial. Am J Gastroenterol. 2018 Jul;113(7):987-997.
3. van der Gaag et al. Preoperative biliary drainage for cancer of the head of the pancreas. N Engl J Med. 2010 Jan 14;362(2):129-37.
4. Tol et al. Metal or plastic stents for preoperative biliary drainage in resectable pancreatic cancer. Gut. 2016 Dec;65(12):1981-1987.
5. Gorris et al. Does same session EUS-guided tissue acquisition and ERCP increase the risk of pancreatitis in patients with malignant distal biliary obstruction? HPB (Oxford). 2022 Apr;18:S1365-182X(22)00098-3.

Disclosure

Jeska A. Fritzsche, Marc G. Besselink, Olivier R.C. Busch and Freek Daams have no conflicts of interest or financial ties to disclose.
Paul Fockens performed as a consultant for Olympus and Cook Endoscopy.
Johanna W. Wilmink reports research grants from Servier, Celgene, Halozyme, Merck, Roche, Pfizer, Amgen and Novartis, and nonfinancial support from MSD and AstraZeneca.
Rogier P. Voermans reports research grants from Boston Scientific and Prion Medical, performed as a consultant for Boston Scientific, and received speaker’s fee from Mylan and Zambon.
Roy L.J. van Wanrooij performed as a consultant for Boston Scientific. All outside the submitted work.

Introduction

Distal malignant biliary obstruction (DMBO) is a serious diagnosis that often results in significant morbidity and mortality due to development of obstructive jaundice and related complications. Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) has been described as a salvage therapy for patients with DMBO following unsuccessful ERCP and/or EUS-guided biliary drainage [1,2]. EUS-GBD leverages the proximity of the gallbladder to the gastrointestinal lumen to establish a new passage for biliary drainage, which offers a viable and potentially safer alternative to current EUS-BD techniques, particularly when the gallbladder is distended [3]. There is a paucity of data reporting on the outcomes of EUS-GBD for this indication, limited by small cohorts an​d single-centre design. We report a multi-centre study of outcomes for EUS-GBD performed for DMBO in non-surgical candidates.

Aims & Methods

A review of a prospectively collected database of 28 EUS-GBD cases was performed between 2017 and 2024 at two referral centres in New Zealand. At both centres, patients were consented for biliary drainage via ERCP, EUS-BD, and/or EUS-GBD prior to sedation so that drainage could be achieved in a single anaesthetic session. Ethics approval was provided at participating centres before commencement. Included participants were adults diagnosed with DMBO who had unsuccessful ERCP and/or EUS-BD, and a patent hepatocystic junction. A transduodenal approach was universal, using electrocautery-enhanced lumen apposing metal stents (LAMS), and propofol-assisted anaesthesia. Technical success (TS), clinical success (CS), length of hospital stay (LOS), adverse events (AEs), reinterventions, and survival were recorded. CS was defined by improvement in biochemistry and symptoms within 72 hours. AEs were categorised into serious and non-serious events. Re-interventions were categorised into early (<7 days) or delayed (≥7 days) procedures. Follow up duration was from time of intervention until patient death.

Results

Mean age was 74 years with 32.1% females. Pancreatic cancer was the most common diagnosis. Mean Charlson comorbidity index was 9.8 ± 1.4 and mean ASA physical status classification was 3.9 ± 0.5. The 10mm LAMS was most commonly used (78.6%), with co-axial plastic stent placement performed in 25%. TS and CS was achieved in all cases. Pre-procedure bilirubin improved from mean 126 ± 115 umol/L to 63 ± 49 umol/L at 72 hours. There were no intra-procedural complications and no early reinterventions recorded. Mean LOS was 3 ± 3 days. There were 9 non-serious AEs, all infective in aetiology and treated with antibiotics. 5 serious AEs were recorded (cholangitis (n=1), recurrent obstruction (n=3) and LAMS obstruction (n=1)) and only these cases required reintervention. These were treated with ERCP (n=1), percutanous drainage (n=3), and stent removal (n=1) respectively. No repeat procedure was required in 23/28 (82.1%) patients. Median cohort survival was 135 days.

Conclusion

EUS-GBD offers excellent TS and CS as a salvage therapy for DMBO in the second or third-line setting. Furthermore, it is safe with a favourable AE profile, short LOS and low rate of reintervention. This is particularly important in this cohort of patients with advanced malignancy. EUS-GBD offers a durable therapy and can be used as destination platform for other DMBO therapeutics. We have also demonstrated feasibility of sequential deployment within the same interventional session as ERCP and EUS-BD procedures creating a streamlined process for limiting cumulative anaesthetic exposures.

References

1. Imai, H., et al., EUS-guided gallbladder drainage for rescue treatment of malignant distal biliary obstruction after unsuccessful ERCP. Gastrointestinal endoscopy, 2016. 84(1): p. 147-151.
2. Debourdeau, A., et al., Effectiveness of endoscopic ultrasound (EUS)‐guided choledochoduodenostomy vs. EUS‐guided gallbladder drainage for jaundice in patients with malignant distal biliary obstruction after failed endoscopic retrograde cholangiopancreatography: Retrospective, multicenter study (GALLBLADEUS Study). Digestive Endoscopy, 2024.
3. Kamal, F., et al., Efficacy and safety of EUS-guided gallbladder drainage for rescue treatment of malignant biliary obstruction: A systematic review and meta-analysis. Endoscopic ultrasound, 2023. 12(1): p. 8-15.

Introduction

For distal malignant biliary obstruction (dMBO) self-expandable metal stents (SEMS) have shown improved patency over plastic stents. Whilst initial data suggest that Covered versus Uncovered SEMS increase Time to Recurrent Biliary Obstruction (TRBO), no data is available for Fully-Covered (FC) versus Partially-Covered (PC) design.

Aims & Methods

Pubmed, Scopus and Cochrane databases were screened from inception to January 2023 for all studies describing adult patients with dMBO, treated by endoscopic placement of FC or PC-SEMS and describing Adverse Events (AEs), Recurrences or TRBO for the specific stent subpopulation. A random-effects meta-analysis was performed following PRISMA checklist, reporting outcomes as pooled proportions or means [95% confidence interval (95%CI)]. Sub-analyses restricted to 1) prospective studies, 2) unresectable diseases, 3) pancreatic cancers were pre-planned. Heterogeneity and Publication bias were explored through I² statistic and LFK index respectively. Standardized differences (d-values) were calculated between the two groups (CRD42023393965).

Results

From 1290 records, 62 studies (3327 patients with FC-SEMS and 2322 patients with PC-SEMS) were included.
Comparison of FC versus PC-SEMS showed negligible differences (d-values<0.1) in the rate of total AEs (12% vs. 9.9%) and all specific adverse events, including cholecystitis (2.5% vs. 2.6%).
In prospective studies, total recurrences were similar between FC-SEMS (21.5% [16.8-26.5], I²=72.5%) versus PC-SEMS (25.6% [20.6-30.9], I²=84.5%), despite small differences (0.117-d-values-0.215) in the rate of ingrowth (0.2% vs 2.8%) favouring FC-SEMS and migration (7% vs 4.3%) favouring PC-SEMS. These results were confirmed amongst unresectable diseases, with even a small difference in total recurrences (30.7% versus 25.9%) favouring PC-SEMS.
In prospective studies, TRBO was estimated to be longer for PC-SEMS (369 [290-449] days, I²=71.9%) versus FC-SEMS (219 [165-273] days, I²=93.3%; d-value=0.129 [small difference]), with consistent results in unresectable diseases.

Conclusion

FC-SEMS and PC-SEMS seem comparable in terms of AEs (including pancreatitis and cholecystitis) and recurrences, as migrations of FC-SEMS are compensated by ingrowths of PC-SEMS. Despite high heterogeneity and small standardized differences, PC-SEMS showed longer patency in prospective studies and amongst unresectable malignancies, potentially advising head-to-head comparison in this scenario.

References

FC-SEMS and PC-SEMS seem comparable in terms of AEs (including pancreatitis and cholecystitis) and recurrences, as migrations of FC-SEMS are compensated by ingrowths of PC-SEMS. Despite high heterogeneity and small standardized differences, PC-SEMS showed longer patency in prospective studies and amongst unresectable malignancies, potentially advising head-to-head comparison in this scenario.