Multicenter Study of the Efficacy and Safety of Electrocautery-Enhanced Lumen-Apposing Metal Stents for the Internal Drainage of Pancreatic Fluid Collections

doi:10.21203/rs.3.rs-3009759/v1

Pancreatic fluid collections (PFCs) including pancreatic pseudocyst (PP) and walled-off necrosis (WON) are complications after pancreatitis. We aimed to evaluate the efficacy and safety of endoscopic ultrasound (EUS)-guided lumen-apposing metal stent (LAMS) placement to manage PFCs. Between June 2019 and May 2023, patients with symptomatic PFCs who underwent EUS-guided electrocautery-enhanced LAMS drainage were enrolled retrospectively from eight tertiary centers in Taiwan. In total, 33 [14 (42.42%) PP and 19 (57.58%) WON] patients were enrolled. Gallstones (27.27%) and abdominal pain (72.73%) were the most common etiology and indication for drainage. The technical and clinical success rates were 100% and 96.97%, respectively. The mean procedure time of 30.55 (±16.17) minutes. Complications included one (3.03%) case of self-limited bleeding without mortality. There were seven (21.21%) patients with recurrence. Patients with disconnected pancreatic duct syndrome (DPDS) had a higher recurrence rate than those without (71.43% vs. 38.46%, p=0.05). After replacing LAMSs with transmural double-pigtail plastic stents (DPSs) in the DPDS patients, the DPS migration rate was higher in the patients with recurrence (100% vs. 33.33%, p=0.04). In conclusion, drainage of symptomatic PFCs with EUS-guided electrocautery-enhanced LAMS is efficient and safe. Replacing LAMS with DPS in DPDS patients was associated with a lower recurrence rate.

Health sciences/Health care/Therapeutics/Therapeutic endoscopy

Health sciences/Gastroenterology/Gastrointestinal diseases/Pancreatic disease/Pancreatitis

endoscopic ultrasound

lumen-apposing metal stent

pancreatitis

pseudocyst

walled-off necrosis

Pancreatic fluid collections (PFCs) are one of the most common complications of acute pancreatitis (AP). After three to four weeks of severe AP, some collections of fluid or necrotic tissue may be encapsulated outside the pancreas, which can lead to the formation of a pancreatic pseudocyst (PP) or walled-off necrosis (WON) [1]. Approximately 20 ~ 30% of patients with AP complicated with persistent PFCs have been reported to have PFC-related symptoms or complications, including fever, infection, abdominal pain, biliary or gastrointestinal tract obstruction, and aneurysm formation, for which interventions are required [2]. Step-up care for symptomatic PFCs includes cessation and control of the offending factors, accompanied with medical therapy such as proton pump inhibitors, somatostatin, pancreatic enzyme supplements, and antibiotics to control infection [2]. However, a substantial proportion of patients with persistent symptomatic PFCs fail conservative treatment and are referred for drainage of infective fluid or removal of necrotic tissues. Conventionally, drainage of PFCs is performed by either percutaneous or surgical methods. The former technique is performed by percutaneous pigtail drainage and the creation of a cutaneous fistula with a self-expandable metal stent followed by necrosectomy, while the latter technique includes either open or laparoscopic necrosectomy and video-assisted retroperitoneal debridement [2–5]. However, percutaneous interventions are associated with a low resolution rate and high re-intervention and recurrence rates, and surgical management is associated with high rates of perioperative mortality and comorbidities, fistula formation, longer hospital stay, and poor quality of life [5–7].

Endoscopic therapy including transpapillary and transmural internal drainage is an alternative to conventional interventions. These endoscopic techniques have a higher clinical success rate compared with percutaneous drainage, and lower risks of multiorgan failure, fistula formation, and shorter hospital stay than surgery [5–7]. Traditional endoscopic internal drainage is performed with transmural fistula creation followed by plastic stenting. However, only infective fluid can be drained into the gastrointestinal tract with plastic stents, while the necrotic tissue remains in the walled-off cavity, leading to persistent symptoms and recurrence. In 2012, Binmoeller et al. published a porcine study using a novel metal stent, the so-called lumen-apposing metal stent (LAMS), to create a communicating tract between two isolated organs [8]. Subsequently, endoscopic ultrasound (EUS)-guided LAMS placement has also been used in several off-label indications with high technical and success rates [9]. Transoral endoscopic necrosectomy for WON can be achieved with the use of LAMSs, which have been shown to be superior to plastic stents in terms of procedure time, need for surgery, and clinical success and recurrence rates [10]. In this multicenter study, we aimed to investigate the efficacy and safety of a novel electrocautery-enhanced LAMS for the management of symptomatic PFCs, and evaluate the predictors of clinical resolution and recurrence.

Study design and endoscopic ultrasound techniques

This retrospective multicenter study was conducted at eight tertiary centers in Taiwan which was approved by the Research Ethics Review Committee of the study institutes (Far Eastern Memorial Hospital FEMH-111171-E, China Medical University Hospital CMUH111-REC2-114, Kaohsiung Chang Gung Memorial Hospital 202201132B0D001, Changhua Christian Hospital CCH210103, Fu Jen Catholic University Hospital FJUH111205, Shin Kong Wo Ho-Su Memorial Hospital 20221012R). All study methods were performed in accordance with the Committee on Publication Ethics guidelines. Codes rather than identifying information of enrolled patients were obtained in this retrospective study and written informed consents were waived (Research Ethics Review Committee of the Far Eastern Memorial Hospital). All data generated or analysed during this study are included in this published article and its supplementary information files. Patients with AP who developed symptomatic PFCs and were treated by internal drainage with EUS-guided transmural LAMS placement (Fig. 1 ~ 4) between June 2019 and May 2023 were enrolled. All procedures were performed by endosonographers with more than 5 years of experience. In this study, we used the Hot AXIOS™ electrocautery-enhanced LAMS (Boston Scientific, Marlborough, MA, USA) for internal drainage. The Hot AXIOS™ is a saddle-shaped braided flexible metal stent which is flanged at both ends and is fully covered by a silicon membrane. The sizes of the PFCs, defined as the proportion of necrotic area in WON, and the distance between the wall of encapsulated PFC and gastrointestinal tract, were evaluated by EUS. Color Doppler was used to avoid intervening vessels at the puncture site and trajectory. Under EUS-guidance, the electrocautery-enhanced delivery system was deployed (autocut mode, 100 W, effect 5, VIO200D, ERBE, Germany) from the gastrointestinal lumen into the PFC, and then the bilateral flanges were deployed in order to approximate the PFC and gastrointestinal wall. After endoscopic and fluoroscopic confirmation of the iatrogenic communicating tract created by the LAMS, the delivery system was removed. If clinically indicated including persistent PCF-related symptoms after LAMS placement, transoral direct endoscopic necrosectomy (DEN) using foreign body retrieval was performed through the LAMS to remove necrotic tissues in pancreatic WON. The LAMS was removed if PFC-related clinical symptoms resolved, and double-pigtail plastic stents (DPSs) were inserted via cysto-gastroenterostomy at the discretion of the endoscopist.

Outcome measurements

Clinical, radiological and endoscopic data were reviewed from medical records. Technical success was defined as the ability to place and deploy a transmural LAMS and observe fluid gushing out under endoscopy after deployment during the index procedure. Clinical success was classified as symptom resolution, defined as disappearance of PFC-related symptoms within the first week of LAMS placement, and radiological resolution, defined as a drained PFC with a size less than 20 mm before LAMS removal. Adverse events (AEs) within 3 days were classified as immediate procedure-related events, and those occurring from 3 days until LAMS removal as delayed complications. Disconnected pancreatic duct syndrome (DPDS) was diagnosed if disrupted pancreatic duct shown in anyone of the following imaging modalities: EUS, endoscopic retrograde pancreatography, or cross-sectional imaging studies including computed tomography and magnetic resonance imaging. Long-term clinical success was defined as complete resolution of the PFC-related symptoms at the last follow-up date. Recurrence was defined as the development of PFC-related symptoms or when the size of the PFC increased after complete resolution with the initial EUS-guided LAMS management.

Statistical analysis

The Student’s t-test and χ2 test or Fisher’s exact test were used to compare continuous and categorical variables, respectively. Continuous variables were expressed as mean (± standard deviation), and categorical variables were expressed as count (%). We divided the subjects into two groups according to PFC recurrence, and univariate logistic regression analysis was used to evaluate the predictors, which were expressed as odds ratio (OR) for outcome assessment. Statistical significance was defined as a two-tailed p value < 0.05. The statistical analysis was performed using STATA software (version 11.0; Stata Corp, College Station, TX, USA). All data generated or analyzed during this study are included in the supplementary file.

The demographic data of the enrolled subjects are shown in Table 1. Thirty-three patients (13 females; 20 males; mean age 53.93 ±15.28 years) with symptomatic PFCs were enrolled. Only three (9.09%) patients did not have comorbidities, while six (18.18%) patients had malignancy (one ovarian cancer, one endometrial cancer, one pancreatic ductal adenocarcinoma, one intraductal papillary mucinous neoplasm and two pancreatic neuroendocrine tumor). The most common etiology of AP was gallstones (27.27%), followed by alcohol (24.24%), hypertriglyceridemia (12.12%), malignancy (15.15%), and others (21.21%, two idiopathic, two drug-related pancreatitis, one trauma, one post-endoscopic retrograde pancreatography and one post-endoscopic papillectomy). Abdominal pain was the most common (72.73%) reason for the intervention, followed by infection (21.021%) and gastric outlet obstruction (6.06%). Fourteen (42.42%) patients had a PP, and 19 (57.58%) had WON. The mean PFC size was 10.77 (±5.48) cm, and the mean necrotic area in WON was 63.50% (±23.46%). Most PFCs were unilocular (75.76%), with Balthazar grades of C (15.15%), D (57.58%) and E (27.27%). Seven (21.21%) patients had paracolic gutter extension of inflammatory fluid collection. The mean follow-up period was 421.97 (± 397.75) days.

Eight (24.24%), ten (30.30%) and fifteen (45.45%) patients underwent EUS-LAMS placement within 1 month, between 1~3 months, and more than 3 months after the onset of AP, respectively (Table 2). Most (66.67%) of the patients had not received an intervention before EUS-LAMS placement, while seven (21.21%) patients had undergone external pigtail drainage, two (6.06%) EUS-guided transmural DPS internal drainage, and two (6.06%) transpapillary pancreatic stenting (TPS) before EUS-LAMS placement. The LAMS size was 15 mm in all patients. The total procedure and puncture-to-deployment times were 30.5 (±16.17) minutes and 5.76 (±7.75) minutes, respectively. The most common transluminal route was from the gastric body (75.76%), followed by the gastric antrum (6.06%) and gastric fundus (6.06%). The technical success and symptom resolution rates were 100%, and the radiological resolution rate was 96.97%. One (3.03%) patient had an early AE of procedure-related intracystic bleeding at 8-hour after the procedure despite clopidogrel withheld for 7 days preoperatively. Fortunately, bleeding resolved after conservative treatment with blood transfusion and intravenous tranexamic acid. Among the patients with WON, a mean 2.65 (±1.98) DEN sessions were performed. Complications during DEN included three (16.67%) cases of self-limited bleeding, two (11.11%) of stent migration, and one (5.56%) of symptomatic pneumoperitoneum. The mean indwelling LAMS time was 25.27 (±10.09) days. Seven (21.21%) patients developed PFC recurrence, of whom two (28.57%) were asymptomatic and the others needed further interventions. The mean recurrence to removal of the LAMS time was 200.29 (±184.11) days.

There were no significant differences in the etiology of pancreatitis, characteristics of the PFCs, and AP onset to LAMS placement time between the patients with and without PFC recurrence (Table 3). However, more of the patients with recurrence had DPDS (71.43% vs. 38.46%, p=0.05). In addition, the patients with DPDS who developed recurrence had a higher migration rate of the replacement transmural DPS after LAMS removal compared to those with resolution (100% vs. 33.33%, p=0.04). Univariate analysis showed that older age (OR 1.02), male sex (OR 1.83), WON type (OR 6.00), paracolic gutter extension (OR 4.13), more sessions of DEN (OR 1.38), presence of DPDS (OR 7.50), and those in whom the LAMS was not replaced with a transmural DPS (OR 2.13) were associated with a higher risk of PFC recurrence, although all without statistical significance (Table 4).

Pancreatic fluid collections are one of the most common complications after severe AP [1]. Traditional approaches for symptomatic PFCs such as percutaneous and surgical interventions are often challenging, with high re-intervention and recurrence rates, peri-operative comorbidities, and mortality [4–5, 7]. With advances in interventional EUS techniques, endoscopic treatment has replaced invasive procedures in the treatment of several biliopancreatic disorders [13]. To our knowledge, this is the first study which demonstrated that the management of symptomatic PFCs after severe AP using EUS-guided internal drainage with an electrocautery-enhanced rather than conventional LAMS system was efficient and safe. Our results showed high technical (100%) and clinical (96.97%) success rates, with a low complication rate (3.03%). The presence of DPDS was associated with recurrence, and we suggest replacing the LAMS with a transmural DPS among patients with DPDS to prevent symptomatic PFC recurrence.

Peripancreatic fluid with interstitial edema can occur in patients with severe AP, and transient organ failure and mortality have been reported in the first 2 weeks after onset [2]. The encapsulated collection of fluid or necrotic tissue has been reported in approximately 6 ~ 20% of patients with AP and 20 ~ 40% of those with chronic pancreatitis after 4 weeks of the disease, and cross-sectional imaging may disclose well circumscribed intra- or extra-pancreatic homogeneous fluid density or non-liquid density, with varying degrees of loculation [1–3, 14–16]. Most patients with chronic PFCs have spontaneous regression and do not require an intervention, however 15 ~ 30% of patients with PP or WON develop symptoms or complications, such as abdominal pain, infection, and biliary or enteral obstruction [2, 3]. Surgical interventions or percutaneous drainage are the traditions standard of care for symptomatic PFCs, however complication and mortality rates of 64 ~ 95% and 6.7 ~ 64.1%, respectively, have been reported in patients undergoing a surgical intervention for PFC [4]. A meta-analysis of 190 patients reported significantly lower risks of new-onset multiorgan failure (OR 0.31, 95% CI 0.10 ~ 0.98), perforations of visceral organs or enterocutaneous fistulae (OR 0.31, 95% CI 0.10 ~ 0.93), and pancreatic fistulae (OR 0.09, 95% CI 0.03 ~ 0.28) as well as a shorter hospital stay in patients who received endoscopic treatment compared to those who underwent surgery [6]. Another meta-analysis of six studies comparing endoscopic and percutaneous drainage of PFCs reported a higher re-intervention and lower resolution rate among patients receiving percutaneous therapy [7]. Therefore, a minimally invasive procedure with an endoscopic approach seems to be superior to conventional surgical and percutaneous methods in terms of clinical succuss, complications, recurrence, and quality of life.

Several modalities of endoscopic therapy are available for PFCs, including EUS-guided transmural cystoenterostomy for internal drainage, transoral endoscopic necrosectomy, and TPS [11]. Binmoeller et al. published a landmark report using a novel lumen-apposing stent to create a gastroenterostomy and facilitate intubation with a gastroscope for further endoscopic treatment in a porcine model [8]. Several specialized LAMSs and delivery devices have subsequently been introduced to provide endoscopists with an alternative to surgical interventions. LAMSs were initially approved in 2013 for the drainage of PP and WON with less than 30% solid debris, and thereafter their use has been expanded to many off-label indications, including gastroenterostomy, biliary and gallbladder drainage, and temporary gastric access for endoscopy [9]. Several clinical studies have demonstrated that EUS-guided internal drainage of symptomatic PFCs with LAMSs is an efficient and safe procedure, with technical and clinical success rates of 91 ~ 100% and 79 ~ 98%, respectively, and a major AE rate of less than 5% [12–18]. Compared with EUS-guided internal drainage using plastic stents, LAMSs have been associated with a higher clinical success rate (88 ~ 100% vs. 80 ~ 92%), shorter procedure time (10.5 ~ 14.9 minutes vs. 21.4 ~ 63.6 minutes), and lower recurrence rate (6.3 ~ 40% vs. 18.8 ~ 41.7%) in many clinical studies [19–23]. A multicenter retrospective study involving 14 institutes and 189 patients found that EUS-guided transmural drainage of WON with LAMSs had a higher clinical success rate (80.4% vs. 57.5%, p = 0.001), shorter procedure time (50.4 minutes vs. 64.6 minutes, p = 0.003), lower need for surgery (5.6% vs. 16.1%, p = 0.023), and lower recurrence rate (5.6% vs. 22.9%, p = 0.036) than plastic stents [10]. When performing DEN for WON, it is sometimes necessary to use multiple plastic stents followed by balloon dilation to create a larger tract for the gastroscope. In contrast, the saddle part of a LAMS has a larger diameter, which provides access for necrosectomy by intubating the transoral gastroscope directly into the PFC. LAMSs have been reported to have a higher DEN success rate compared to plastic stents (80.4% vs. 57.5%, p = 0.001) [10]. Taken together, these findings suggest that LAMSs can achieve more rapid control of infection and symptoms with less recurrence than plastic stents.

The recurrence of PFCs and clinical success after EUS-guided drainage have been associated with the proportion of necrotic area in WON and the presence of DPDS. Maringhini et al. reported that more than 60% of their patients with a solid necrotic area of over 50% required more than three DEN sessions [24]. In addition, the clinical success rate of EUS-guided drainage has been reported to be lower in patients with WON and a necrotic area of more than 40% (OR 0.10, 95% CI 0.02 ~ 0.60, p = 0.01) [25]. Several adjunct methods of DEN for WON have been reported in the literature, including using local instillation or nasocystic tube irrigation with normal saline, hydrogen peroxide, streptokinase or antibiotics [26, 27]. However, none of them have been recommended as an appropriate technique for DEN due to limited evidence [28]. After the resolution of PP and complete clearance of necrotic parts in WON with a collapsed cavity, the LAMS should be removed as soon as possible to prevent delayed complications. Regarding the timing of LAMS removal, an expert panel recommended removal at a mean time of 4.59 weeks [7]. However, the presence of DPDS, which is associated with a higher recurrence rate, should be investigated before LAMS removal. A retrospective review reported that 48 (50%) (6 PP and 42 WON) of 96 PFC patients had DPDS, and that those in whom DPSs were replaced with LAMSs had a lower recurrence rate (5% vs. 37%, p = 0.011) [29]. In addition, TPS was found to be associated with a higher rate of successful clinical outcomes in patients with DPDS (76.5% vs. 22.2%, p = 0.014) in a prospective study of 31 patients with DPDS [30]. Thus, in patients with DPDS, long-term indwelling of transmural DPSs may be necessary to prevent recurrence, and transpapillary bridging of the disrupted main pancreatic duct if possible is recommended before removal of the transmural stent.

There are several limitations to this study. First, it was a retrospective study with a relatively small sample size. Because of reimbursement issues with the costly accessories associated with LAMSs in Taiwan, the number of candidate patients was limited. Therefore, we conducted this study at multiple centers and further studies about the cost-effectiveness compared with other treatment modalities are warranted. Second, the practices used for the management of symptomatic PFCs were unique to each institute. Hence, our findings may not be generalizable to all centers. Third, not all of the enrolled patients underwent investigations for the presence of DPDS before LAMS removal and replacement with transmural DPSs. Additionally, more than half (57.58%) of the enrolled patients with PFCs had WON with a mean necrotic proportion of 63.50%. Thus, the recurrent rate (21.21%) was higher than that reported in the literature.

In conclusion, EUS-guided internal drainage and endoscopic therapy via electrocautery-enhanced LAMSs for symptomatic PFCs is an efficient and safe procedure. Before LAMS removal, investigations for the presence of DPDS and replacement with transmural DPSs is important to avoid recurrence. Further well-designed studies are warranted to compare this method with others and elucidate the appropriate indwelling times of the LAMSs and replacement plastic stents.

AUTHOR CONTRIBUTIONS: Conception and design of the study: C-S C, H-P W. Generation, collection, assembly, analysis and/or interpretation of data: C-S C, Y-T K, Y-C C, Y-C L, C-Y Y, K-C C, S-C L, C-K S,Y-C L, H-P W. Drafting or revision of the manuscript: C-S C, H-P W. Approval of the final version of the manuscript: C-S C, Y-T K, Y-C Chiu, Y-C L, C-Y Y, K-C C, S-C L, C-K S,Y-C L, H-P W.

ACKNOWLEDGEMENTS: None.

CONFLICTS OF INTEREST: All of the authors have no conflicts of interest or financial ties to disclose.

Banks, P.A. et al. Classification of acute pancreatitis–2012: revision of the Atlanta classification and definitions by international consensus. Gut 62(1):102–111 (2013).
Forsmark, C.E., Vege, S.S., Wilcox, C.M. Acute Pancreatitis. N Engl J Med. 375(20):1972–1981 (2016).
Lankisch, P.G., Weber-Dany, B., Maisonneuve, P., Lowenfels, A.B. The Natural Course of Pancreatic Pseudocysts Following a First Attach of Acute Pancreatitis (the 39th Annual Meeting of the American Pancreatic Association). Pancreas 37:479 (2008).
Mier, J., León, E.L., Castillo, A., Robledo, F., Blanco, R. Early versus late necrosectomy in severe necrotizing pancreatitis. Am J Surg. 173(2):71–75 (1997).
Sgaramella, L., Gurrado, A., Pasculli, A., Prete, F.P., Catena, F., Testini, M. Open necrosectomy is feasible as a last resort in selected cases with infected pancreatic necrosis: a case series and systematic literature review. World J Emerg Surg. 15(1):44 (2020).
Haney, C.M. et al. Endoscopic versus surgical treatment for infected necrotizing pancreatitis: a systematic review and meta-analysis of randomized controlled trials. Surg Endosc. 34(6):2429–2444 (2020).
Szakó, L.et al. Endoscopic and surgical drainage for pancreatic fluid collections are better than percutaneous drainage: Meta-analysis. Pancreatology 20(1):132–141 (2020).
Binmoeller. K.F., Shah, J.N. Endoscopic ultrasound-guided gastroenterostomy using novel tools designed for transluminal therapy: a porcine study. Endoscopy 44(5):499–503 (2013).
Choi, J.H.et al. Effectiveness and Safety of Lumen-Apposing Metal Stents in Endoscopic Interventions for Off-Label Indications. Dig Dis Sci. 67(6):2327–2336 (2022).
Chen, Y.I. et al. Lumen apposing metal stents are superior to plastic stents in pancreatic walled-off necrosis: a large international multicenter study. Endosc Int Open. 7(3):E347-E354 (2019).
Jagielski, M., Jackowski, M. The Role of Endoscopic Transpapillary Stenting of the Main Pancreatic Duct during the Endoscopic Treatment of Pancreatic Fluid Collections. J Clin Med. 10(4):761 (2021).
Aburajab, M., Smith, Z., Khan, A., Dua, K. Safety and efficacy of lumen-apposing metal stents with and without simultaneous double-pigtail plastic stents for draining pancreatic pseudocyst. Gastrointest Endosc. 87(5):1248–1255 (2018).
Adler, D.G. et al. Placement of lumen-apposing metal stents to drain pseudocysts and walled-off pancreatic necrosis can be safely performed on an outpatient basis: A multicenter study. Endosc Ultrasound. 8(1):36–42 (2019).
Fugazza, A. et al. International multicenter comprehensive analysis of adverse events associated with lumen-apposing metal stent placement for pancreatic fluid collection drainage. Gastrointest Endosc.91(3):574–583 (2020).
Hammad, T. et al. Efficacy and Safety of Lumen-Apposing Metal Stents in Management of Pancreatic Fluid Collections: Are They Better Than Plastic Stents? A Systematic Review and Meta-Analysis. Dig Dis Sci. 63(2):289–301 (2018).
Kumta, N.A. et al. EUS-guided drainage of pancreatic fluid collections using lumen apposing metal stents: An international, multicenter experience. Dig Liver Dis. 51(11):1557–1561 (2019).
Teoh, A.W.B. et al. Prospective multicenter international study on the outcomes of a newly developed self-approximating lumen-apposing metallic stent for drainage of pancreatic fluid collections and endoscopic necrosectomy. Dig Endosc 32(3):391–398 (2020).
Yang, D. et al. Safety and rate of delayed adverse events with lumen-apposing metal stents (LAMS) for pancreatic fluid collections: a multicenter study. Endosc Int Open. 6(10):E1267-E1275 (2018).
Falk, V., Kenshil, S., Sandha, S., Teshima, C., D'Souza, P., Sandha, G. The Evolution of EUS-Guided Transluminal Drainage for the Treatment of Pancreatic Fluid Collections: A Comparison of Clinical and Cost Outcomes with Double-Pigtail Plastic Stents, Conventional Metal Stents and Lumen-Apposing Metal Stents. J Can Assoc Gastroenterol. 3(1):26–35 (2018).
Ge, P.S., Young, J.Y., Jirapinyo, P., Dong, W., Ryou, M., Thompson, C.C. Comparative Study Evaluating Lumen Apposing Metal Stents Versus Double Pigtail Plastic Stents for Treatment of Walled-Off Necrosis. Pancreas 49(2):236–241 (2020).
Guzmán-Calderón, E., Chacaltana, A., Díaz, R., Li, B., Martinez-Moreno, B., Aparicio, J.R. Head-to-head comparison between endoscopic ultrasound guided lumen apposing metal stent and plastic stents for the treatment of pancreatic fluid collections: A systematic review and meta-analysis. J Hepatobiliary Pancreat Sci. 29(2):198–211 (2022).
Shin, H.C., Cho, C.M., Jung, M.K., Yeo, S.J. Comparison of Clinical Outcomes between Plastic Stent and Novel Lumen-apposing Metal Stent for Endoscopic Ultrasound-Guided Drainage of Peripancreatic Fluid Collections. Clin Endosc. 52(4):353–359 (2019).
Yang, J. et al. Lumen-apposing stents versus plastic stents in the management of pancreatic pseudocysts: a large, comparative, international, multicenter study. Endoscopy 51(11):1035–1043 (2019).
Seicean, A. et al. What is the Impact of the Proportion of Solid Necrotic Content on the Number of Necrosectomies during EUS-Guided Drainage using Lumen-Apposing Metallic Stents of Pancreatic Walled-off Necrosis ? J Gastrointestin Liver Dis. 29(4):623–628 (2020).
Zhu, H., Xie, P., Wang, Y., Jin, Z., Li, Z., Du, Y. The role of solid debris in endoscopic ultrasound-guided drainage of walled-off necrosis: A large cohort study. J Gastroenterol Hepatol. 35(12):2103–2108 (2020).
Lariño-Noia, J. et al. Endoscopic drainage with local infusion of antibiotics to avoid necrosectomy of infected walled-off necrosis. Surg Endosc. 35(2):644–651 (2021).
Messallam, A.A. et al. Direct Endoscopic Necrosectomy With and Without Hydrogen Peroxide for Walled-off Pancreatic Necrosis: A Multicenter Comparative Study. Am J Gastroenterol. 116(4):700–709 (2021).
Guo, J. et al. A multi-institutional consensus on how to perform endoscopic ultrasound-guided peri-pancreatic fluid collection drainage and endoscopic necrosectomy. Endosc Ultrasound. 6(5):285–291 (2017).
Pawa, R., Dorrell, R., Russel, G., Gilliam, J., Mishra, G., Pawa, S. Long-term transmural drainage of pancreatic fluid collections with double pigtail stents following lumen-apposing metal stent placement improves recurrence-free survival in disconnected pancreatic duct syndrome. Dig Endosc. 34(6):1234–1241 (2022).
Chen, Y. et al. Endoscopic transpapillary drainage in disconnected pancreatic duct syndrome after acute pancreatitis and trauma: long-term outcomes in 31 patients. BMC Gastroenterol. 19(1):54 (2019).

Table 1. Demographic data of the enrolled subjects and characteristics of the PFCs.

Variables	Patients with symptomatic PFCs (n=33)
Age, mean±SD (range), years	53.93 ± 15.28 (20~87)
Sex, female/male, n (%)	13 (39.39) / 20 (60.61)
BMI, mean±SD, kg/m²(range)	24.13 ± 4.99 (17.00 ~37.66)
Comorbidities, n (%) None Cardiovascular disease Cerebrovascular disease Chronic liver disease Chronic kidney disease Hypertension/DM/Hyperlipidemia Malignancy	3 (9.09) 6 (18.18) 3 (9.09) 5 (15.15) 2 (6.06) 23 (69.69) 6 (18.18)
Etiology of pancreatitis, n (%) Gallstones Alcohol Hypertriglyceridemia Malignancy^* Others^#	9 (27.27) 8 (24.24) 4 (12.12) 5 (15.15) 7 (21.21)
Symptoms of the PFC, n (%) Abdominal pain Infection GI tract obstruction	24 (72.73) 7 (21.21) 2 (6.06)
Types of PFC, n (%) Pseudocyst Walled-off necrosis Proportion of necrotic area, mean±SD (range), %	14 (42.42) 19 (57.58) 63.50 ± 23.46 (30.00~90.00)
Size of the PFC, mean±SD (range), cm	10.77 ± 5.48 (3.30~25.00)
Characteristics of the PFC, n (%) CT Balthazar grade (A/B/C/D/E) Unilocular/Multilocular (communicating/non-communicating) Paracolic gutter extension	0 (0) / 0 (0) / 5 (15.15) / 19 (57.58) / 9 (27.27) 25 (75.76) / 8 (24.24) [4 (50.00) / 4 (50.00)] 7 (21.21)
Follow-up period, mean±SD (range), days	421.97 ± 397.75 (65~2,065)

Abbreviations: BMI, body mass index; CT, computed tomography; DM, diabetes mellitus; GI, gastrointestinal; PFC, pancreatic fluid collection.

^*Patients with malignancy: ovarian cancer (n=1), intraductal papillary mucinous neoplasm (n=1), pancreatic ductal adenocarcinoma (n=1), pancreatic neuroendocrine tumor (n=2).

^# Other etiologies of pancreatitis: idiopathic (n=2), drug-related pancreatitis (n=2), post-endoscopic retrograde pancreatography (n=1), post-papillectomy (n=1), trauma (n=1).

Table 2. Details of the EUS-guided LAMS placement procedures.

Variables

Patients with symptomatic PFCs (n=33)

Time from onset of AP to LAMS placement, mean±SD (range), days

≤1 month, n (%)

1~3 months, n (%)

> 3 months, n (%)

166.50 ± 306.42 (18~1,284)

8 (24.24)

10 (30.30)

15 (45.45)

Previous intervention before LAMS placement, n (%)

No treatment

External drainage

EUS-guided transmural DPS

Transpapillary pancreatic stent

Surgery

22 (66.67)

7 (21.21)

2 (6.06)

0 (0)

Size of the LAMS, n (%)

10 mm

15 mm

20 mm

0 (0)

33 (100)

0 (0)

Procedure time, mean±SD (range), minutes

Total procedure

Puncture-to-deployment

30.55 ± 16.17 (13~72)

5.76 ± 7.75 (2~45)

Transmural route, n (%)

Transgastric

Antrum

Body

Fundus

Transduodenal

2 (6.06)

28 (75.76)

2 (6.06)

1 (3.03)

Technical success, n (%)

33 (100)

Clinical success, n (%)

Symptoms resolved

Radiologically resolved

Symptoms and radiologically resolved

33 (100)

32 (96.97)

Adjunct therapy, n (%)

Concurrent external drainage

Concurrent transmural DPS

Hydrogen peroxide instillation

Nasocystic tube

6 (18.18)

2 (6.06)

0 (0)

Index procedure-related complications, n (%)

Bleeding

Cyst rupture

Infection

Stent migration

Mortality

Others

1 (3.03)

0 (0)

DEN session, mean±SD (range), times

2.65 ± 1.98 (0~7)

Accessories used for DEN, n (%)

Patients underwent DEN

Pentapod grasper alone

Combination

18 (54.55)

9/18 (50.00)

DEN-related complications, n (%)

Self-limited bleeding

Stent migration

Pneumoperitoneum

3 / 18 (16.67)

2 / 18 (11.11)

1 / 18 (5.56)

LAMS indwelling time, mean±SD (range), days

25.27 ± 10.09 (3~44)

Recurrence, n (%)

Asymptomatic without treatment

EUS-DPS

Use of antibiotics

External drainage

Surgery

EUS-LAMS

7 / 33 (21.21)

2 / 7 (28.57)

1 / 7 (14.29)

0 (0)

Recurrence time after LAMS removal, mean±SD (range), days

200.29 ± 184.11 (28~542)

Abbreviations: AP, acute pancreatitis; DEN, direct endoscopic necrosectomy; DPS, double-pigtail stent; EUS, endoscopic ultrasound; LAMS, lumen-apposing metal stent; PFC, pancreatic fluid collection.

Table 3. Clinical outcomes of the enrolled subjects.

Variables

Resolution (n=26)

Recurrence (n=7)

P value

Etiology of pancreatitis, n (%)

Gallstones

Alcohol

Hypertriglyceridemia

Malignancy

Others

5 (19.23)

7 (26.92)

3 (11.54)

5 (19.23)

6 (23.08)

4 (57.14)

1 (14.29)

0 (0)

1 (14.29)

0.10

Characteristics of the PFC, n (%)

CT Balthazar grade (C/D/E)

Unilocular / Multilocular

Communicating / Non-communicating

5 (19.23) / 14 (53.85) / 7 (26.92)

18 (69.23) / 8 (30.77)

22 (84.62) / 4 (15.38)

0 (0) / 5 (71.42) / 2 (28.57)

7 (100.00) / 0 (0)

7 (100) / 0 (0)

0.49

0.10

0.28

Type of PFC, PP / WON, n (%)

13 (50.00) / 13 (50.00)

1 (14.29) / 6 (85.71)

0.04

Size of the PFC, mean±SD, cm

10.61 ± 5.89

11.36 ± 3.84

0.75

Time of onset to LAMS placement, mean±SD, days

Less than 1 month, n (%)

More than 1 months, n (%)

145.42 ± 247.12

7 (26.92)

19 (73.08)

256.86 ± 455.96

1 (14.29)

6 (57.14)

0.39

0.49

Presence of DPDS, n (%)

10 (38.46)

5 (71.43)

0.05

Variables

Patients with DPDS and resolution (n=10)

Patients with DPDS and recurrence (n=5)

P value

Transmural DPS after LAMS removal, n (%)

Migration

6 (60.00)

2 / 6 (33.33)

4 (80.00)

4 / 4 (100.00)

0.44

0.04

Transpapillary pancreatic stent after LAMS removal, n (%)

Migration

6 (60.00)

4 / 6 (66.67)

2 (40.00)

0 / 2 (0.00)

0.58

0.10

Concurrent transpapillary pancreatic stent and transmural DPS after LAMS removal, n (%)

4 (40.00)

2 (40.00)

1.00

Abbreviations: DPDS, disconnected pancreatic duct syndrome; DPS, double-pigtail stent; LAMS, lumen-apposing metal stent; PFC, pancreatic fluid collection; PP, pancreatic pseudocyst; WON, walled-off necrosis.

Table 4. Univariate analysis for the predictors of PFC recurrence.

Variables	Odds ratio	95% confidence interval	P value
Age (every 1 year)	1.02	0.96~1.08	0.57
Male sex	1.83	0.30~11.26	0.51
PFC size (every 1 cm)	1.02	0.88~1.19	0.75
PFC type (WON vs. PP)	6.00	0.63~57.06	0.12
WON necrotic area	1.00	0.96~1.05	0.85
Paracolic gutter extension	4.13	0.66~25.90	0.13
DEN session	1.38	0.83~2.30	0.22
Presence of DPDS	7.50	0.76~74.16	0.09
Without transmural DPS after LAMS removal	2.13	0.39~11.59	0.38

Abbreviations: DEN, direct endoscopic necrosectomy; DPDS, disconnected pancreatic duct syndrome; DPS, double-pigtail stent; LAMS, lumen-apposing metal stent; PFC, pancreatic fluid collection; PP, pancreatic pseudocyst; WON, walled-off necrosis.

No competing interests reported.

LAMSforPFCmulticenter.xlsx

Multicenter Study of the Efficacy and Safety of Electrocautery-Enhanced Lumen-Apposing Metal Stents for the Internal Drainage of Pancreatic Fluid Collections

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Abstract

Figures

INTRODUCTION

METHODS

Study design and endoscopic ultrasound techniques

Outcome measurements

Statistical analysis

RESULTS

DISCUSSION

Declarations

References

Tables

Additional Declarations

Supplementary Files

Status:

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