Endoscopic ultrasound guided gallbladder drainage—is it time to change practice?

Laparoscopic cholecystectomy remains the standard of care for management of acute cholecystitis (AC). Historically, in patients with AC who are deemed high risk for surgery, percutaneous cholecystostomy also known as percutaneous transhepatic gall bladder drainage (PT-GBD) was performed as a bridge to delayed cholecystectomy. In the 2018 Tokyo guidelines for management of AC, PT-GBD was recommended as a standard approach for gallbladder drainage in high risk surgical candidates (Recommendation Grade 1, Level B). It also recommended consideration of endoscopic transhepatic gall bladder drainage (ETGBD) or endoscopic ultrasound guided gall bladder drainage (EUS-GBD) in high-volume institutes with therapeutic EUS expertise (Level B) (1).

In a recent publication in Gut, Teoh et al. reported results of an international multicenter randomized control trial (RCT) comparing outcomes of EUS-GBD vs. PT-GBD in management of AC in high risk surgical patients (2). This study included a total of 80 patients enrolled from August 2014 to February 2018. The study reported that EUS-GBD significantly reduced 1-year adverse events, 30-day adverse events, re-interventions (after 30 days), number of unplanned readmissions and recurrent cholecystitis. Also, the post procedural pain score and analgesic requirement were significantly lower with EUS-GBD. The technical success, clinical success and 30-day mortality were statistically similar between EUS-GBD and PT-GBD. The mean procedural time and median hospital stay were not significantly different. The results are summarized in Table 1.

Based on their results, the authors concluded that EUS-GBD significantly improved outcomes compared to PT-GBD in patients with AC who are high risk for surgery. They propose that EUS-GBD should be the procedure of choice in centers with therapeutic EUS expertise in patients who are not candidates for future cholecystectomy.

In a previous RCT comparing EUS-GBD vs. PT-GBD in management of AC in patients who are deemed high risk for surgery, Jang et al. reported similar rates of technical (97% vs. 97%; 95% one-sided CI lower limit, −7%, P values =0.001 for noninferiority margin of 15%) and clinical success (100% vs. 96%; 95% one-sided CI lower limit, −2%, P=0.0001 for noninferiority margin of 15%) (3). As the adverse event rates were similar between the two groups, the study established EUS-GBD as an effective non-inferior alternative to PT-GBD. A recent systematic review and meta-analysis of comparative studies reported that EUS-GBD had similar rates of success but lower morbidity in terms of adverse events, re-interventions and shorter hospital stay compared to PT-GBD (4). The current RCT by Teoh et al. reports superiority of EUS-GBD over PT-GBD in management of AC in patients who are high risk surgical candidates.

Compared to pancreatic fluid collections, EUS guided drainage of gallbladder is technically more challenging, as gallbladder is not fixed in relation to stomach or duodenum. Hence, in addition to basic skills in EUS, expertise in therapeutic EUS is necessary for EUS-GBD. Previous studies have assessed the learning curves for performance of EUS-GBD. Tyberg et al. suggested a minimum of 19 cases to achieve expertise in EUS-GBD (5). In a larger study by Teoh et al. (6), endoscopists’ experience of fewer than 25 procedures was a significant predictor of 30-day adverse events. Hence, one should consider structured training program in interventional EUS or perform adequate number of EUS-GBD procedures (20–25 procedures) under expert supervision before performing it in individual practice (7).

The risk of complications with EUS-GBD include perforation, bile leak and stent dislodgement. The availability of lumen apposing metal stents (LAMS) and cautery enhanced stent delivery system has helped improved the safety of EUS-GBD. However, one has to realize that if an adverse event like perforation or stent migration occurred needing surgical intervention, the mortality rates would be high, as these patients were high-risk surgical candidates to begin with. Hence, in addition to availability of expertise in therapeutic EUS, EUS-GBD procedures should be performed in centers where an experienced surgical team, who can manage potential iatrogenic complications is available. Endoscopists should take surgical backup into consideration before performing EUS-GBD in individual practice.

It has to be highlighted that none of the patients in the current RCT underwent cholecystectomy CCY. There is limited data on feasibility and safety of CCY after EUS GBD. Saumoy et al. compared outcomes of CCY after EUS GBD and PT GBD (8). They reported 100% technical success and no differences in the rates of open vs. laparoscopic CCY. There was no difference in postoperative adverse events. At current time, EUS-GBD should be offered exclusively to patients who will not be candidates for future CCY, until further studies establish the safety of CCY after EUS-GBD.

In the current RCT, only 4 patients did not undergo 1-month follow up endoscopy after initial EUS-GBD. The other 27 patients underwent follow up per-oral cholecystoscopy with removal of gallstones. It is possible that the results of the current RCT cannot be replicated in clinical practice, if the follow-up endoscopy for removal of gallstones and LAMS is not routinely performed. Currently, there is no consensus on the need for removing the LAMS after the initial EUS-GBD procedure. Limited data is available on long-term outcomes of EUS-GBD. Few retrospective studies have reported that it is safe to leave the LAMS in place indefinitely (9,10). While some experts have recommended exchange of LAMS with double pigtail plastic stents (11), individual patients’ risk of anesthesia for follow up endoscopy needs to considered instead of routine removal of LAMS in all patients who have undergone EUS-GBD.

It is to be noted that the EUS-GBD in the current RCT was performed exclusively using LAMS with a cautery enhanced stent delivery system from a single manufacturer ((AXIOS, Boston Scientific Medical Corporation, Marlborough, USA). The cautery enhanced delivery system removes the need for dilation of puncture track and helps reduce the risk of adverse events (12). The wide caliber of LAMS also enables spontaneous passage of gallstones and direct cholecystoscopy in follow-up procedures for removal of gallstones. The safety profile of EUS-GBD in real life may not be similar to current RCT results if tubular stents or thinner caliber stents are used for EUS-GBD.

As the authors acknowledge, the RCT did not compare cost effectiveness between EUS-GBD and PT-GBD. Despite the higher cost of initial EUS-GBD procedure from dedicated devices and expertise, the authors suspect that it is more cost effective due to significantly lower number of re-interventions and re-admissions. A previous modeling study suggested that endoscopic GBD was more cost effective than PT-GBD because of shorter hospital stay and lower re-admission rates (13). However, further studies on cost effectiveness is needed prior to widespread change in clinical practice.

Given that LAMS are expensive, one could argue that ET-GBD with plastic stents is a cheaper endoscopic alternative to PT-GBD. However, in a recent meta-analysis by Krishnamoorthi and Jayaraj et al. (14), EUS-GBD was associated with higher technical, clinical success and lower rates of recurrent cholecystitis when compared to ET-GBD. ET-GBD may have a special role in patients with ascites, those needing ERCP for other reasons and who are potential future candidates for surgery. Another limitation of the current RCT is the lack of assessment of quality of life measurements. The authors state that they were unable to perform it, as the patients were old, fragile and could not comprehend questionnaires. While it might be challenging to obtain this data, it is needed before recommending widespread change in clinical practice.

While the recent RCT by Teoh et al. reports EUS-GBD as a superior approach compared to PT-GBD in management of AC in patients who are deemed high risk for surgery, we have not reached a point where EUS-GBD can replace PTGBD as the standard of care. At current time, EUS-GBD could be considered as first line approach for definitive treatment for AC in patients who will never be good surgical candidate for CCY in future and if expertise in therapeutic EUS is available. Further data are needed on long-term efficacy of EUS-GBD, safety of CCY after EUS-GBD and cost-effectiveness of EUS-GBD.

Acknowledgments

Funding: None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Digestive Medicine Research. The article did not undergo external peer review.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/dmr-20-68). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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References

1. Mori Y, Itoi T, Baron TH, et al. Tokyo Guidelines 2018: management strategies for gallbladder drainage in patients with acute cholecystitis (with videos). J Hepatobiliary Pancreat Sci 2018;25:87-95. [Crossref] [PubMed]
2. Teoh AYB, Kitano M, Itoi T, et al. Endosonography-guided gallbladder drainage versus percutaneous cholecystostomy in very high-risk surgical patients with acute cholecystitis: an international randomised multicentre controlled superiority trial (DRAC 1). Gut 2020;69:1085-91. [PubMed]
3. Jang JW, Lee SS, Song TJ, et al. Endoscopic ultrasound-guided transmural and percutaneous transhepatic gallbladder drainage are comparable for acute cholecystitis. Gastroenterology 2012;142:805-11. [Crossref] [PubMed]
4. Luk SW, Irani S, Krishnamoorthi R, et al. Endoscopic ultrasound-guided gallbladder drainage versus percutaneous cholecystostomy for high risk surgical patients with acute cholecystitis: a systematic review and meta-analysis. Endoscopy 2019;51:722-32. [Crossref] [PubMed]
5. Tyberg A, Jha K, Shah S, et al. EUS-guided gallbladder drainage: a learning curve modified by technical progress. Endosc Int Open 2020;8:E92-E96. [Crossref] [PubMed]
6. Teoh AY, Perez-Miranda M, Kunda R, et al. Outcomes of an international multicenter registry on EUS-guided gallbladder drainage in patients at high risk for cholecystectomy. Endosc Int Open 2019;7:E964-E973. [Crossref] [PubMed]
7. Teoh AYB. EUS-guided gallbladder drainage: is it so easy? Endosc Int Open 2020;8:E97-E98. [Crossref] [PubMed]
8. Saumoy M, Tyberg A, Brown E, et al. Successful Cholecystectomy After Endoscopic Ultrasound Gallbladder Drainage Compared With Percutaneous Cholecystostomy, Can it Be Done? J Clin Gastroenterol 2019;53:231-5. [Crossref] [PubMed]
9. Yuste RT, García-Alonso FJ, Sánchez-Ocana R, et al. Safety and clinical outcomes of endoscopic ultrasound-guided gallbladder drainage with lumen-apposing metal stents in patients with dwell time over one year. Ann Gastroenterol 2019;32:514-21. [PubMed]
10. Choi JH, Lee SS, Choi JH, et al. Long-term outcomes after endoscopic ultrasonography-guided gallbladder drainage for acute cholecystitis. Endoscopy 2014;46:656-61. [PubMed]
11. Kamata K, Takenaka M, Kitano M, et al. Endoscopic ultrasound-guided gallbladder drainage for acute cholecystitis: Long-term outcomes after removal of a self-expandable metal stent. World J Gastroenterol 2017;23:661-7. [Crossref] [PubMed]
12. Krishnamoorthi R, Irani S. EUS guided gallbladder drainage using lumen apposing metal stents. Techniques in Gastrointestinal Endoscopy 2019;150652.
13. Corral JE, Das A, Krӧner PT, et al. Cost effectiveness of endoscopic gallbladder drainage to treat acute cholecystitis in poor surgical candidates. Surg Endosc 2019;33:3567-77. [Crossref] [PubMed]
14. Krishnamoorthi R, Jayaraj M, Thoguluva Chandrasekar V, et al. EUS-guided versus endoscopic transpapillary gallbladder drainage in high-risk surgical patients with acute cholecystitis: a systematic review and meta-analysis. Surg Endosc 2020;34:1904-13. [Crossref] [PubMed]