Original Article

Volume 18, Number 1, February 2025, pages 1-11

Analysis of Adverse Events of Endoscopic Ultrasound-Guided Lumen-Apposing Metal Stent Placement: Insights Across Various Indications and Techniques

Advances in interventional endoscopy, particularly in the area of endoscopic ultrasound (EUS)-guided approaches, have altered treatment protocols for gastrointestinal and pancreaticobiliary disorders. Device improvements along with advances in endoscopic techniques now allow minimally invasive therapeutic approaches for treating complex disorders affecting regions beyond the gastrointestinal system. For example, endoscopic transmural drainage has traditionally been carried out under endoscopic guidance alone, which requires a somewhat blind approach that has been associated with a higher risk of complications such as bleeding and perforation. But thanks to the development of the EUS, these endoscopic procedures are now carried out under imaging guidance, greatly improving accuracy and safety [1]. Currently, a variety of important procedures can be carried out with EUSs, including biliary tree and gallbladder drainage, endohepatology interventions, creation of gastrointestinal anastomoses, radiofrequency ablation of tumors, injection of medications for the treatment of tumors and cancer-related pain, and management of local complications of acute pancreatitis [2].

The first transmural EUS-guided biliary tree drainage was performed in 2001 in a patient with a pancreatic head mass [3]. Since then, the development of EUS-guidance has led to ongoing advances in endoscopic procedures and technologies for transmural drainage. In particular, one important development was the introduction of self-expanding metal stents and lumen-apposing metal stents (LAMSs) to be used during EUS-guided drainage procedures [2]. While LAMSs were first introduced in 2012, they were not widely available until 2015. The first reported application of LAMS in humans involved five patients with acute cholecystitis and 15 patients with symptomatic pancreatic pseudocysts, all of whom had contraindications to surgery and were treated successfully [4]. Notably, EUS-guided procedures that include LAMS placement incur similar adverse event (AE) risks as any other advanced endoscopic procedure. But importantly, timely identification of any complication that may be associated with an endoscopic procedure is crucial for mitigating morbidity and mortality. Also, complications associated with stent placement can vary in severity and timing, sometimes occurring immediately after stent deployment, yet often occurring well after the procedure. However, reports on the safety of LAMSs are limited and highly varied, and some studies have observed complication rates of up to 20% [5].

Therefore, considering our lack of understanding regarding the short-term and long-term complications associated with EUS-guided LAMS placement, we performed a single-center, retrospective cross-sectional study to explore the procedural features, clinical outcomes, and AE rates in patients who received this procedure. Furthermore, we specifically explored whether certain AEs were associated with specific procedural strategies, including the concomitant use of LAMSs with plastic stents, implementation of LAMS dilation, and the combined application of LAMS dilation with the use of plastic stents. Our comprehensive characterization of the procedural features and clinical outcomes for patients having EUS-guided LAMS placement will help to optimize therapeutic guidelines and risk stratification approaches for patients with biliary, pancreatic, and gastrointestinal conditions requiring stents for anastomosis and fluid drainage.

We performed a retrospective cross-sectional study of all adult patients (≥ 18 years old) who underwent EUS-guided LAMS placement interventions from January 2015 to December 2023 at Henry Ford Hospital (Detroit, MI). Only patients under 18 years of age were excluded from the study. Patients were identified from the Henry Ford Health endoscopic procedure database. All patients had a biliary-gastrointestinal connection or drainage created with LAMS placement per one of nine procedures and were followed for at least 30 days after the initial procedure. This study was approved by the Henry Ford Health Institutional Review Board, and the requirement for informed consent was waived. Patient confidentiality was maintained throughout the study. The study was conducted in compliance with the ethical standards of the responsible institution on human subjects as well as with the Helsinki Declaration.

The main outcomes were AEs associated with EUS-guided LAMS placement and defined per a modified version of the American Society for Gastrointestinal Endoscopy lexicon for endoscopic AEs [6]. AEs were further categorized as being early (within 48 h of the procedure) or delayed (between 48 h and 30 days after the procedure). Secondary outcomes included the following: technical success defined as successful placement of the LAMS; clinical success with no needed intervention defined as improvement in clinical outcomes; specific clinical outcomes (e.g., cholecystitis resolved); and multiple clinical consequences within three categories (i.e., hospital stay/admission, need for clinical intervention, serious outcomes including death and permanent disability).

Baseline characteristics of the study population, EUS-guided procedures, technical details, and procedure outcomes were summarized as mean with standard deviation (SD) for continuous data and as frequencies and proportions for categorical data. To determine AEs associated with various EUS-guided LAMS placement strategies, patients were stratified via three schemes and compared: 1) LAMS placement with a concomitant plastic stent versus LAMS placement with no plastic stent used during the initial LAMS placement procedure, 2) LAMS dilation versus no LAMS dilation during the main LAMS placement procedure, 3) combination of LAMS dilation with a plastic stent versus LAMS dilation only with no plastic stent during the LAMS placement procedure. Chi-square test was used to determine the differences between groups in categorical variables. For continuous variables, t-tests or Wilcoxon rank sum tests were used depending on the data distributions. A P value of < 0.05 was considered statistically significant. Statistical analyses were performed using the Statistical Package for the Social Sciences (IBM v20.0, Armonk, NY) software.

There were 243 patients who underwent EUS-guided LAMS interventions during the study period, including 133 (54.7%) men and 110 (45.3%) women. The mean age was 53.7 ± 15.9 years. Most patients were White (65.4%) or Black (18.1%) people. The mean body mass index (BMI) for the study population was 30.0 ± 9.5 kg/m², with more than half of the population being in the overweight range (n = 163, 67.1%). There were 108 (44.4%) patients who were active smokers, and the most common comorbidity was hypertension in 117 (48.1%) patients (Table 1).

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Table 1. Sociodemographic and Health Behavior Characteristics of Patients Who Had EUS-Guided LAMS Placement

The most common indication for LAMS placement was pancreatic fluid collections in 170 (70%) patients, followed by gastric outlet obstruction in 27 (11.1%) patients, and the most frequently performed biliary-gastrointestinal connection type was cystogastrostomy in 159 (65.4%) patients. The most common LAMS size was 20 × 10 mm in a little over half of the patients. Plastic stents were implemented in conjunction with the LAMS in 176 patients (72.4%), and 145 patients (59.7%) had the LAMS dilated during the initial procedure. For the patients who had LAMS dilation, the mean maximum diameter of dilation was 13.2 ± 2.7 mm. The mean procedure time was 62.9 ± 31.5 min, and the maximal cyst/fluid collection diameter prior to the LAMS placement was 97.2 ± 40.2 mm (Table 2).

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Table 2. Procedural Features, Success Rates and Outcomes, and Clinical Consequences and Serious Outcomes of Patients Who Had EUS-Guided LAMS Placement

Procedures for almost all patients were technically successful (n = 237, 97.5%), and the overall rate of clinical success was 93% (n = 226) across all interventions (Table 2). There were 219 (90.1%) patients who had no clinical post-procedural consequences; however, nine (3.7%) patients required intensive care unit admission for more than one night, eight (3.3%) patients required a blood transfusion, two (0.8%) patients developed a permanent disability, and mortality occurred in five (2.1%) patients (Table 2).

Table 3 outlines the success and AE rates in patients for the five most frequently performed procedures, with the most commonly employed procedure being cystogastrostomy in 158 patients and the least employed being cystoduodenostomy in 10 patients. Of note, across these five procedures, technical success rates were high, occurring at rates between 90% and 100%, and clinical success rates ranged from 88% to 95%. Cystoduodenostomy done in the 10 patients showed the lowest rate of early AEs (1/10, 10%) but the highest rate of late AEs (4/10, 40%). The highest rate of early AEs occurred in the 31 patients who had gastro-jejunostomy (8/31, 25%); whereas the lowest rate of late AEs was 19% in patients who underwent both gastrojejunostomy (6/31) and cholecystoduodenostomy (3/16).

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Table 3. Procedural Success and Complication Rates by Anastomosis Procedural Approach for Patients Who Had EUS-Guided LAMS Placement

Out of the six patients who did not achieve technical success, four patients had AEs, two patients had early AEs (stent migration and misdeployment), and two patients had both early and late AEs (i.e., perforation, abdominal pain and hypoxia, infection and abdominal pain).

Of the 243 patients, 96 (39.5%) experienced at least one of 155 AEs, with 48 patients (19.7%) having at least one early AE and 70 patients (28.8%) having at least one late AE. The most common early AE was abdominal pain in 28 (11.5%) patients, followed by bleeding in nine (3.7%) patients, and infection in six (2.5%) patients. The most common late AE was abdominal pain in 25 (10.3%) patients, followed by infection in 13 (5.3%), bleeding in 10 (4.1%), and stent occlusion in 10 (4.1%). Of the total 96 patients who experienced AEs, most had mild AEs (75/96, 78.1%), whereas 16.6% (16/96) experienced moderate AEs, and 5.2% had severe AEs (5/96) (Table 4).

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Table 4. AEs Experienced by Patients Who Had EUS-Guided LAMS Placement

We asked whether the addition of a plastic stent alongside a LAMS might be associated with certain AEs. A comparison between patients who had the added plastic stent versus those who had no plastic stent showed that of the 176 patients with plastic stents, 85 had at least one AE, while 20 of the 67 patients with no plastic stent had at least one AE, indicating a significantly higher rate of AEs in those with the addition of a plastic stent (48.3% vs. 29.9%; P = 0.009). A significantly higher proportion of patients who had plastic stents included in their procedure had a late AE (33.0% vs. 17.9%; P = 0.021), but groups did not differ in regard to early AEs (20.5% vs. 17.9%; P = 0.656). The most common late complication was abdominal pain in 22 (12.5%) patients who underwent plastic stent placement with a LAMS. Notably, perforation occurred at a significantly higher rate in those who had LAMS placement alone than in those who underwent LAMS and plastic stent placement (3.0% vs. 0%; P = 0.021), while stent occlusion occurred at a higher rate in the group with plastic stent inclusion (5.7% vs. 0%; P = 0.046) (Table 5).

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Table 5. A Comparison of AE Rates in Patients Who Had EUS-Guided LAMS Placement With or Without Concomitant Plastic Stents, and in Patients Who Had EUS-Guided LAMS Placement With or Without Dilation

We next asked whether having the LAMS dilated might be associated with certain AEs. Of the 146 patients who underwent LAMS dilation during the same procedure as the initial LAMS placement, 64 had an AE; whereas 41 of the 97 patients who did not have LAMS dilation had an AE (43.8% vs. 42.6%; P = 0.809). While the dilation group had a significantly higher rate of late AEs (34.2% vs. 20.6%; P = 0.022), the rate of early AEs did not differ between groups (17.1% vs. 23.7%; P = 0.207). Notably, the rate of stent occlusion was greater in the LAMS dilation group than in the non-dilation group (6.2% vs. 1.0%, P = 0.049) (Table 5).

Lastly, we asked whether LAMS dilation in combination with a plastic stent was associated with different rates of AEs compared to LAMS dilation without an additional stent. Of the 146 patients who underwent LAMS dilation, 125 had an added plastic stent placed, and 21 had no added plastic stent. Of those with LAMS dilation and the added plastic stent, 56 experienced at least one AE, while five of the 21 patients with no added plastic stent had AEs. There was no statistically significant difference in the rates of AEs between the two groups (45.1% vs. 25%, P = 0.090) (Table 6). Furthermore, this analysis showed that there was no statistically significant difference between the two groups in the rates of early AEs (17.6% vs. 9.5%; P = 0.975) or late AEs (36.81% vs. 19.0%; P = 0.905). No other clinically relevant differences were seen between groups for specific AEs (Table 6).

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Table 6. A Comparison of AE Rates in Patients Who Had EUS-Guided LAMS With Dilation, With or Without Concomitant Plastic Stent Placement

In this retrospective cross-sectional study of patients who had EUS-guided LAMS placement for a range of indications and through a variety of procedural strategies, we observed that EUS-guided LAMS placement procedures had high technical and clinical success rates ranging over 93%. The rate of AEs was 39.5%, which is comparable to previous studies [5]. LAMS dilation was associated with a higher risk of late AEs and stent occlusion, and plastic stent placement alongside a LAMS was associated with higher rates of overall AEs, late AEs, and stent occlusion. Most AEs were mild to moderate, and the mortality rate was 2.1%.

Endoscopic transmural drainage is a commonly used technique for gallbladder drainage and is also the standard practice for managing symptomatic pancreatic fluid collections, for which LAMSs were first authorized. Thus, most studies on the usage of LAMSs concern these indications [7-12]. In this study, we sought to determine the rate of AEs associated with LAMS placement across a wide range of indications and interventions. To the best of our knowledge, no previous studies have looked at the types of AEs associated with LAMSs across various procedures. The technical and clinical success rates we observed are in line with previous studies and suggest a high level of utility for the LAMS approach [8-10, 13]. Also, several of our more detailed observations align with what has been seen before. For example, the most common indication for LAMS placement in our cohort was pancreatic fluid collection [8], and the rates of early and late AEs ranged between 20% to 30% [5]. Importantly, the specific procedural complications of stent occlusion and migration occurred late in approximately 3% to 4% of patients, which has also been reported previously [8].

However, misdeployment was encountered in one patient in our study, whereas previous studies have reported it at a rate of up to 5.8% [2].

Notably, of the AEs that did occur, most were mild to moderate, although one patient remained intubated after the procedure due to worsening respiratory status and had a cardiac arrest 4 days later. However, we did observe a 2% post-procedural mortality rate, highlighting the fact that even though EUS-guided procedures are typically safe and successful, they are not without some serious risks. It is important to note that the mortality rate might be underestimated due to the retrospective nature of the study.

Almost two-thirds of our patients had plastic stent placement along with LAMS, and of these, almost half showed complications. The rate of overall AEs and late AEs in this group was higher than what was previously reported [8]; this may be due to the fact that previous studies have investigated AEs associated predominantly with pancreatic fluid collections, whereas our study looked at a wider range of indications. Notably, we observed that the rate of stent occlusion was higher in patients who had plastic stent placement, which contradicts the theoretical benefit of placing coaxial plastic stents in the inner channel of the LAMS to prevent occlusion [14]. The higher rate of stent occlusion in patients with plastic stent placement inside the LAMS may be attributed to several factors. Mechanically, the addition of a coaxial plastic stent reduces the effective diameter of the LAMS, potentially increasing the risk of clogging with debris or necrotic material. Furthermore, plastic stents are more prone to biofilm formation, which, combined with debris, may accelerate occlusion compared to the LAMS alone [15]. The design mismatch between the coaxial plastic stent and the LAMS could create irregularities that trap debris, while the narrowed inner channel may disrupt the laminar flow of secretions, contributing to stasis. Additionally, the theoretical benefit of the plastic stent in preventing tissue in-growth or excessive debris accumulation might be offset by its tendency to act as a bottleneck, particularly at the interface with the LAMS. These factors could explain why the anticipated reduction in occlusion risk was not observed in practice. Therefore, when plastic stents are employed, physicians should be aware that occlusion may still occur, and signs and symptoms of occlusion should not be ignored.

Rates of late AEs were significantly higher in patients who had LAMS dilation than in patients with no LAMS dilation, most notably stent occlusion, while dilation was not associated with an increased risk of early AEs. We hypothesize that this finding may be due to tissue edema resulting from manipulation during LAMS dilation and subsequent tissue regeneration, which could lead to stent obstruction that would not be apparent soon after the procedure. This suggests that patients who have LAMS dilation during the procedure should be monitored specifically for occlusion and other complications that may arise from the healing process.

To further explore the role of LAMS dilation on AE rates, we asked whether patients who had LAMS dilation with concomitant plastic stent placement had different rates of AEs compared to those with LAMS dilation alone, wondering if the combination of procedural effects might have a greater influence on AEs. However, we found no difference in the rates of AEs between patients who had plastic stent placement along with LAMS dilation versus those who only had LAMS dilation, highlighting no synergistic influences associated with these combined procedural features.

Our study had some limitations. It was a retrospective study that was performed in a single, high-volume, quaternary-care center, which may have introduced potential bias in patient selection. The follow-up care was not standardized, resulting in varying symptom assessments. Another limitation of this study is the follow-up period of at least 30 days, which may be too brief to capture late AEs. Longer follow-up is needed to better assess long-term outcomes. Despite being the largest single-center study reporting on this topic, the study may still lack sufficient power to detect small differences in outcomes. Although this was a retrospective study, all data were complete, and no records were missing data.

In summary, the use of LAMSs led to high technical and clinical success rates across different indications and interventions. The rate of overall AEs was 39%, and most AEs were mild and moderate. Although plastic stent placement alongside a LAMS is done to avoid stent occlusion, the rate of stent occlusion was higher in patients who had plastic stents placed in addition to the LAMS. Notably, LAMS dilation was also associated with a higher risk of stent occlusion. Our findings suggest that EUS-guided LAMS placement may be a safe and effective technique for pancreatic and biliary drainage, and other indications. More studies are needed to investigate the full safety profile of LAMS use for various biliary and gastrointestinal indications.

Acknowledgments

We would like to express our sincere gratitude to the multidisciplinary team at Henry Ford Hospital including the gastroenterologists, endoscopy nurses, and radiology technicians, for their invaluable expertise and support throughout this study. Their dedication to patient care and procedural excellence was instrumental in facilitating this research. We also extend our appreciation to the patients whose experiences and outcomes contributed significantly to the findings of this study.

Financial Disclosure

Andrew Watson is a consultant for Cook Medical. Cyrus Piraka received grant/research support from Aries, US Endoscopy and the National Institutes of Health (NIH). Sumit Singla and Tobias Zuchelli are consultants from Boston Scientific.

Conflict of Interest

The authors declare that they have no conflict of interest.

Informed Consent

Not applicable. Hospital database was used to pull data retrospectively.

Author Contributions

Mohammed Abusuliman contributed to manuscript writing, drafting, designing and critical revision of the manuscript. Taher Jamali contributed to data collection, and the conception and design of the manuscript. Faisal Nimri, Ammad Javaid Chaudhary, Khaled Elfert, Abdulmalik Saleem, Ahmad Alomari, Muhammad Saad Faisal, Omar Shamaa, Mark Obri, Ahmed E. Salem, Amr Abusuliman, Andrew Watson, Robert Pompa, Duyen Dang, Cyrus Piraka, Mazen Elatrache, Sumit Singla and Tobias Zuchelli contributed to the conception and design of the manuscript.

Data Availability

The data supporting the findings of this study are available from the corresponding author upon reasonable request.

Abbreviations

AE: adverse event; EUS: endoscopic ultrasound; LAMS: lumen-apposing metal stent; SD: standard deviation; COPD: chronic obstructive pulmonary disease; ERCP: endoscopic retrograde cholangiopancreatography; EDGE: endoscopic ultrasound-directed transgastric ERCP; BMI: body mass index; ICU: intensive care unit

1. Rana SS, Shah J, Kang M, Gupta R. Complications of endoscopic ultrasound-guided transmural drainage of pancreatic fluid collections and their management. Ann Gastroenterol. 2019;32(5):441-450.
   doi pubmed
2. Armellini E, Metelli F, Anderloni A, Cominardi A, Aragona G, Marini M, Pace F. Lumen-apposing-metal stent misdeployment in endoscopic ultrasound-guided drainages: A systematic review focusing on issues and rescue management. World J Gastroenterol. 2023;29(21):3341-3361.
   doi pubmed
3. Giovannini M, Moutardier V, Pesenti C, Bories E, Lelong B, Delpero JR. Endoscopic ultrasound-guided bilioduodenal anastomosis: a new technique for biliary drainage. Endoscopy. 2001;33(10):898-900.
   doi pubmed
4. Itoi T, Binmoeller KF, Shah J, Sofuni A, Itokawa F, Kurihara T, Tsuchiya T, et al. Clinical evaluation of a novel lumen-apposing metal stent for endosonography-guided pancreatic pseudocyst and gallbladder drainage (with videos). Gastrointest Endosc. 2012;75(4):870-876.
   doi pubmed
5. Choi JH, Kozarek RA, Larsen MC, Ross AS, Law JK, Krishnamoorthi R, Irani S. Effectiveness and safety of lumen-apposing metal stents in endoscopic interventions for off-label indications. Dig Dis Sci. 2022;67(6):2327-2336.
   doi pubmed
6. Cotton PB, Eisen GM, Aabakken L, Baron TH, Hutter MM, Jacobson BC, Mergener K, et al. A lexicon for endoscopic adverse events: report of an ASGE workshop. Gastrointest Endosc. 2010;71(3):446-454.
   doi pubmed
7. Shah RJ, Shah JN, Waxman I, Kowalski TE, Sanchez-Yague A, Nieto J, Brauer BC, et al. Safety and efficacy of endoscopic ultrasound-guided drainage of pancreatic fluid collections with lumen-apposing covered self-expanding metal stents. Clin Gastroenterol Hepatol. 2015;13(4):747-752.
   doi pubmed
8. Mohan BP, Jayaraj M, Asokkumar R, Shakhatreh M, Pahal P, Ponnada S, Navaneethan U, et al. Lumen apposing metal stents in drainage of pancreatic walled-off necrosis, are they any better than plastic stents? A systematic review and meta-analysis of studies published since the revised Atlanta classification of pancreatic fluid collections. Endosc Ultrasound. 2019;8(2):82-90.
   doi pubmed
9. Bang JY, Hawes RH, Varadarajulu S. Lumen-apposing metal stent placement for drainage of pancreatic fluid collections: predictors of adverse events. Gut. 2020;69(8):1379-1381.
   doi pubmed
10. Bang JY, Hasan M, Navaneethan U, Hawes R, Varadarajulu S. Lumen-apposing metal stents (LAMS) for pancreatic fluid collection (PFC) drainage: may not be business as usual. Gut. 2017;66(12):2054-2056.
    doi pubmed
11. Siddiqui AA, Kowalski TE, Loren DE, Khalid A, Soomro A, Mazhar SM, Isby L, et al. Fully covered self-expanding metal stents versus lumen-apposing fully covered self-expanding metal stent versus plastic stents for endoscopic drainage of pancreatic walled-off necrosis: clinical outcomes and success. Gastrointest Endosc. 2017;85(4):758-765.
    doi pubmed
12. Zeissig S, Sulk S, Brueckner S, Matthes K, Hohmann M, Reichel S, Ellrichmann M, et al. Severe bleeding is a rare event in patients receiving lumen-apposing metal stents for the drainage of pancreatic fluid collections. Gut. 2019;68(5):945-946.
    doi pubmed
13. Stefanovic S, Degroote H, Hindryckx P. Reduction of lams-related adverse events with accumulating experience in a large-volume tertiary referral center. J Clin Med. 2023;12(3):1037.
    doi pubmed
14. AbiMansour JP, Jaruvongvanich V, Velaga S, Law RJ, Storm AC, Topazian MD, Levy MJ, et al. Lumen-apposing metal stents with or without coaxial plastic stent placement for the management of pancreatic fluid collections. Gastrointest Endosc. 2024;99(1):104-107.
    doi pubmed
15. Vaishnavi C, Samanta J, Kochhar R. Characterization of biofilms in biliary stents and potential factors involved in occlusion. World J Gastroenterol. 2018;24(1):112-123.
    doi pubmed

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