ORIGINAL ARTICLE

Combined Drainage and Protocolized Necrosectomy Through

a Coaxial Lumen-apposing Metal Stent for Pancreatic
Walled-off Necrosis
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A Prospective Multicenter Trial

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Barham K. Abu Dayyeh, MD, MPH,*✉ Vinay Chandrasekhara, MD,*

Raj J. Shah, MD,† Jeffrey J. Easler, MD,‡ Andrew C. Storm, MD,*
Mark Topazian, MD,* Michael J. Levy, MD,* John A. Martin, MD,*
Bret T. Petersen, MD,* Naoki Takahashi, MD,* Steven Edmundowicz, MD,†
Hazem Hammad, MD,† Mihir S. Wagh, MD,† Sachin Wani, MD,†
John DeWitt, MD,† Benjamin Bick, MD,† Mark Gromski, MD,‡
Mohammad Al Haddad, MD, MSc,‡ Stuart Sherman, MD,‡
Ambreen A. Merchant, MBBS,§ Joyce A. Peetermans, PhD,¶ Ornela Gjata, MS,¶
Edmund McMullen, MMath,¶ and Field F. Willingham, MD, MPH§

follow-up. Primary endpoints were probability of radiographic resolution

Objective: We evaluated a protocolized endoscopic necrosectomy
by 60 days and procedure-related serious adverse events.
approach with a lumen-apposing metal stent (LAMS) in patients with
Results: Forty consecutive patients were enrolled September 2018 to
large symptomatic walled-off pancreatic necrosis (WON) comprising
March 2020, of whom 27 (67.5%) were inpatients and 19 (47.5%) had
significant necrotic content, with or without infection.
clinical evidence of infection at their index procedure. Mean WON size
Summary Background Data: Randomized trials have shown similar effi-
was 15.0 ± 5.6 cm with mean 53.2% ± 16.7% solid necrosis. Radio-
cacy of endoscopic treatment compared with surgery for infected WON.
graphic WON resolution was seen in 97.5% (95% CI, 86.8%, 99.9%) by
Design: We conducted a regulatory, prospective, multicenter single-arm
60 days, without recurrence in 34 patients with 6-month follow-up data.
clinical trial examining the efficacy and safety of endoscopic ultrasound
Mean time to radiographic WON resolution was 34.1 ± 16.8 days.
-guided LAMS with protocolized necrosectomy to treat symptomatic
Serious adverse events occurred in 3 patients (7.5%), including sepsis,
WON ≥6 cm in diameter with >30% solid necrosis. After LAMS place-
vancomycin-resistant enterococcal bacteremia and shock, and upper
ment, protocolized WON assessment was conducted and endoscopic
gastrointestinal bleeding. There were no procedure-related deaths.
necrosectomy was performed for insufficient WON size reduction and
Conclusions: Endoscopic ultrasound-guided drainage with protocolized
persistent symptoms. Patients with radiographic WON resolution to ≤ 3
endoscopic necrosectomy to treat large symptomatic or infected walled-
cm and/or 60-day LAMS indwell had LAMS removal, then 6-month

*Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester,
MN; From the †Division of Gastroenterology and Hepatology, Uni-
versity of colorado Anschutz Medical Campus, Aurora, CO; †Division of
Gastroenterology and Hepatology, indiana University School of Medi-
cine, indianapolis, IN; §Division of Digestive Diseases, Department of
Medicine, Emory University, Atlanta, GA; and ¶Endoscopy Division,
Boston Scientific Corporation, Marl-borough, MA.
✉ abudayyeh.barham@mayo.edu.
Grant support: Boston Scientific Corporation.
The data, analytic methods, and study materials for this study may be made available
to other researchers in accordance with the Boston Scientific Data Sharing Policy
(http://www.bostonscientific.com/en-US/data-sharing-requests.html).
B.A., R.S., J.E., F.W.: study concept and design, procedure development,
acquisition of data, first manuscript draft, interpretation of results, study
supervision. V.C., A.C.S., M.T., M.L., J.M., B.P., N.K., S.E., H.H., M.S.
W., S.W., J.DeW., B.B., M.G., M.A.H., S.S.: acquisition of data, inter-
pretation of results. A.M.: interpretation of results. J.P.: study concept and
design, first manuscript draft, interpretation of results, obtained funding,
administrative, technical or material support, study supervision. O.G.:
study concept and design, first manuscript draft, interpretation of results. E.
M.: statistical analysis, first manuscript draft, interpretation of results. All
authors provided critical revision of the manuscript and approved the final
draft. B.A.: research grant and consultation fee from Boston Scientific
Corporation, research support from Medtronic, education/lecture fees from
Olympus. V.C.: Advisory Board of interpace Diagnostics and shareholder
in Nevakar Corporation. Consultant for Covidien, LP. R.S.: Advisory
Board Member, Consultant, and recipient of unrestricted educational
grant, and research grant from Boston Scientific, inc, and Advisory Board
Member, Consultant, and recipient of unrestricted educational grant from
Olympus, Inc. J.E.: consultant activities for Boston Scientific. B.P.: inves-
tigator relationship with Boston Scientific Corporation and AMBU. con-
sultant fees from Olympus America and Pentax; A.C.S.: consultant/inves-
tigator relationship with Boston Scientific, Apollo Endosurgery,
Enterasense, and Endo-TAGSS; consultant fees from ERBE and GI
Dynamics. S.E.: Olympus Consulting and Medical Advisory Board par-
ticipation and Boston Scientific sponsored research at the University of
Colorado. H.H.: consultant fees for Olympus. M.S.W.: consultant for
Boston Scientific, Olympus and Medtronic. S.W.: consultant for Boston
Scientific, Medtronic, Interpace, Cernostics, Exact Sciences. JDe.W.
reports consultant for Boston Scientific and research grant from
Vyaire, Inc. M.G.: consultant for Boston Scientific. M.A.H.: research,
teaching support, and consultation fees from Boston Scientific. S.S.: con-
sultant for Boston Scientific, Olympus and Cook. J.P., O.G., and E.M. are
full-time employees of Boston Scientific Corporation. F.W.: research
funding to the institution from Steris/CSA Medical, Cancer Prevention
Pharmaceuticals, Boston Scientific, and Cook Medical.
All other authors report no conflicts of interest.
Supplemental Digital Content is available for this article. Direct URL citations
appear in the printed text and are provided in the HTML and PDF ver-
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This is an open access article distributed under the terms of the Creative
Commons Attribution-Non Commercial-No Derivatives License 4.0
(CCBY-NC-ND), where it is permissible to download and share the work
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ISSN: 0003-4932/23/27705-e1072
DOI: 10.1097/SLA.0000000000005274

e1072 | www.annalsofsurgery.com Annals of Surgery  Volume 277, Number 5, May 2023

 Annals of Surgery  Volume 277, Number 5, May 2023
off necrotic pancreatic collections was highly effective and safe. Clin-
icaltrials.-gov no: NCT03525808.
Keywords: drainage, metal stents, pancreatic fluid collection, pancreatitis,
plastic stents
(Ann Surg 2023;277:e1072–e1080)
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A cute necrotizing pancreatitis develops in 10% to 20% of cases
of acute pancreatitis, with associated mortality of up to 20%
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to 30% if infection develops in the necrotic collection.1 Walled-
off necrosis (WON) are mature, encapsulated collections of
pancreatic, and/or peripancreatic necrosis with well-defined
inflammatory walls.2 WON develops in approximately 1% to 9%
of acute pancreatitis cases, usually 4 to 6 weeks after the initial
episode of acute pancreatitis.3 One-third of patients with initially
asymptomatic WON later develop symptoms or complications
requiring intervention.4
For symptomatic or infected WON, endoscopic ultrasound
(EUS)-guided drainage using double-pigtail plastic stents (DPPS)
or lumen-apposing metal stents (LAMS) is recognized as a first-line
treatment.1,5 Randomized controlled trials6–8 have shown similar
efficacy for endoscopic management compared with surgical
treatment for infected WON; however, symptomatic patients with
a large necrotic burden regardless of infection are understudied.
Because size and necrotic burden predict the need for mechanical
debridement after endoscopic drainage,9–12 further prospective
investigation of these factors is warranted. In patients with infected
or sterile pancreatic necrosis with persistent organ dysfunction or
failure to thrive, necrosectomy debridement may be considered.1
However, because direct endoscopic necrosectomy (DEN) is
invasive, time-consuming, and carries risks for SAEs such as
infection, bleeding, and perforation,1,13 it is often reserved for
patients with inadequate response to endoscopic transmural
drainage and/or with large amounts of solid or infected necrosis.1,14
An evidence-based, protocolized management approach to endo-
scopic WON with a significant burden of solid necrosis, using
appropriately timed necrosectomy, may improve outcomes.
To further examine endoscopic management of high-risk
patients with WON, we conducted a regulatory prospective mul-
ticenter, single-arm clinical trial evaluating endoscopic manage-
ment of WON with a solid component >30% using large caliber
LAMS and a rigorous and protocolized treatment algorithm.
METHODS
Study Design
We conducted a prospective, regulatory, multicenter, sin-
gle-arm clinical trial to evaluate the safety and efficacy of
endoscopic management for WON ≥6 cm in size (with place-
ment of EUS-guided LAMS with/without endoscopic necrosec-
tomy), adherent to the gastric or bowel wall, and containing
>30% solid necrosis [US Food and Drug Administration (FDA)
IDE#: G170261]. The LAMS (AXIOS Stent and Electrocautery
Enhanced Delivery System, Boston Scientific Corporation,
Marlborough, MA) is cleared in the US for transgastric or
transduodenal endoscopic drainage of symptomatic pancreatic
pseudocysts ≥6 cm in size and WON ≥ 6 cm in size with ≥ 70%
fluid content that are adherent to the gastric or bowel wall. Once
placed, the larger LAMS function as an access port allowing
passage of standard and therapeutic endoscopes to facilitate
debridement, irrigation, and cystoscopy.15 The LAMS is
intended for implantation up to 60 days and is typically removed
upon confirmation of WON resolution. Three sizes of LAMS
Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.
Pancreatic Walled-off Necrosis
were available in the trial (10, 15, and 20 mm diameter), but only
the 15 and 20 mm were used given the selection of complex
WON with large solid necrotic debris burden.
Patient Population
Eligible patients were adults aged 22 to 75 years with severe
or moderately severe acute necrotizing pancreatitis as defined per
the 2012 Revised Atlanta Classification,2 with intrapancreatic
and/or extrapancreatic infected WON or symptomatic sterile
WON ≥ 6cm in size with >30% solid necrotic material demon-
strated by imaging, who were eligible for endoscopic transluminal
drainage. Exclusion criteria included a diagnosis of pseudocysts,
cystic neoplasms, untreated pseudoaneurysms >1 cm within the
WON, >1 WON clearly separated and requiring drainage, prior
surgical, interven-tional radiology or endoscopic treatment of
WON, coagulopathy, intervening gastric varices or unavoidable
blood vessels within the access tract, WON ≥1 cm away from the
GI lumen, WONs with deep pelvic or paracolic gutter necrosis,
prior true anaphylactic reaction to contrast agents, potential or
current pregnancy, current participation in a conflicting inves-
tigational drug or device study.
All investigational sites obtained approval from their local
Institutional Review Boards prior to recruitment of participants
for the clinical study. The study was registered in the Clin-
icalTrials.gov database (NCT03525808) on May 16, 2018 and
was conducted under an FDA-approved protocol (IDE
#G170261). Recruitment and enrollment were conducted
September 2018 to March 2020. Enrolled patients provided written
informed consent for their procedures and study participation. The
study sponsor conducted independent on-site monitoring visits to
all study sites to assess data integrity and continued compliance
with the protocol and applicable regulations.
Endoscopic Protocol
A curvilinear echoendoscope was used to examine the
pancreas and WON. LAMS (AXIOS Stent and Electrocautery
Enhanced Delivery System, Boston Scientific Corporation,
Marlborough, MA) were placed under endosonographic guid-
ance with fluoroscopy. During the index LAMS placement
procedure, lavage and/or morcellation (using a snare or ther-
apeutic endoscopic forceps) of the necrosis was permitted under
endoscopic visualization for up to 20 minutes to clear the
drainage path through the LAMS. No formal necrosectomy was
performed at the index drainage procedure. Investigators could
place an additional LAMS in separate locations (ie, multigate-
way technique) at their discretion if the initial access site was
deemed unfavorable for subsequent endoscopic necrosectomy
access, or to enhance drainage. In addition, placement of a single
7 Fr double-pigtail plastic stent (7 Fr Advanix Biliary Stent;
Boston Scientific Corporation, Marlborough, MA) coaxial
through the LAMS was allowed by the FDA protocol to prevent
early LAMS occlusion from impacted necrosis.
Study Visits
Consecutive eligible patients underwent baseline screening
to report relevant clinical history, and had computed tomography
(CT) or magnetic resonance imaging (MRI) imaging to estimate
the WON percent necrosis and detect pseudoaneurysms (treated
before study participation). Imaging was reviewed at each study
site. An initial WON resolution assessment with repeat CT scan or
MRI was performed at 7 ± 3 days for inpatients and 14 ± 5 days
for outpatients after the index drainage procedure. If WON size
reduction was deemed insufficient and/or if the patient displayed
persistent or new symptoms attributable to the WON collection
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FIGURE 1. Patient flow through the study.

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 Annals of Surgery  Volume 277, Number 5, May 2023 Pancreatic Walled-off Necrosis

TABLE 1. Index Procedural Characteristics (N = 40)

Percent (n/N) or Mean ± SD (n) (range)
Variable Inpatient (n = 27) Outpatient (n = 13) All (n = 40)
Antibiotics given 96.3% (26/27) 100.0% (13/13) 97.5% (39/40)
WON characteristics
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WON measurement—long axis (cm) 12.9 ± 6.2 (26) 10.3 ±3.6 (13) 12.0 ± 5.6 (39)
(6.4,31.0) (6.0,17.9) (6.0,31.0)
WON measurement—short axis (cm) 9.4 ± 3.3 (26) 8.0 ± 2.9 (13) 8.9 ± 3.2 (39)
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(4.5,18.0) (3.2,13.7) (3.2,18.0)

WON % necrotic material 50.4 ± 18.5 (26) 49.9 ± 16.2 (13) 50.3 ± 17.5 (39)
(30.0,90.0) (35.0,95.0) (30.0,95.0)
Wall characteristics
Soft 18.5% (5/27) 23.1% (3/13) 20.0% (8/40)
Fibrotic 25.9% (7/27) 30.8% (4/13) 27.5% (11/40)
Thickened 51.9% (14/27) 46.2% (6/13) 50.0% (20/40)
Thin 3.7% (1/27) 0.0% (0/13) 2.5% (1/40)
Sign of infection*
Fever 14.8% (4/27) 7.7% (1/13) 12.5% (5/40)
Leukocytosis 40.7% (11/27) 15.4% (2/13) 32.5% (13/40)
Visualization of gas bubble within necrotic tissue on CT imaging 29.6% (8/27) 7.7% (1/13) 22.5% (9/40)
No sign of infection 37.0% (10/27) 84.6% (11/13) 52.5% (21/40)
Infection is consistent with:
Localized WON infection 51.9% (14/27) 15.4% (2/13) 40.0% (16/40)
Systemic infection/sepsis 7.4% (2/27) 0.0% (0/13) 5.0% (2/40)
Nutrition source/status*
Nasoenteric 3.7% (1/27) 7.7% (1/13) 5.0% (2/40)
Nasogastric 3.7% (1/27) 0.0% (0/13) 2.5% (1/40)
Nasoduodenal/nasojejunal 22.2% (6/27) 0.0% (0/13) 15.0% (6/40)
Percutaneous endoscopic gastrostomy 3.7% (1/27) 0.0% (0/13) 2.5% (1/40)
Unassisted oral feeding 66.7% (18/27) 76.9% (10/13) 70.0% (28/40)
Total parenteral nutrition (TPN) 3.7% (1/27) 15.4% (2/13) 7.5% (3/40)
*Rows not mutually exclusive; patient could have more than 1 listed item.
SIRS indicates systemic inflammatory response syndrome; WON, walled-off necrosis.

despite LAMS drainage, DEN (limited to 60 min) was performed.
Subsequent to each intervention, a clinical WON assessment with
repeat CT or MRI was performed at 7 ± 3 days for inpatients and
14 ± 5 days for outpatient until radiographic WON size decreased
to <3 cm. LAMS removal was planned within 60 days after
LAMS placement upon evidence of symptomatic and radio-
graphic (CT or MRI) resolution of WON, followed by an in-office
visit or phone call 7 ± 3 days later. A final WON recurrence
assessment visit was performed at 6 months ± 14 days from the
time of LAMS removal, including assessment for presence of
clinical symptoms with further diagnostics ordered per standard of
care. Patients were considered lost to follow-up if they remained
unresponsive to communication after 3 documented attempts by
study staff.

FIGURE 2. Primary efficacy and safety end-

points (ITT analysis, N = 40).

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 Abu Dayyeh et al Annals of Surgery  Volume 277, Number 5, May 2023

TABLE 2. Efficacy Endpoints (ITT Analysis, N = 40)

Percent (n/N) or Mean ± SD (n) (range)
Variable Inpatient (n = 27) Outpatient (n = 13) All (n = 40)
Radiographic resolution of WON to ≤ 3 cm by:
60 d post-LAMS placement 96.3% (26/27) 100.0% (13/13) 97.5% (39/40)
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[95% CI, 81%, 99.9%] [95% CI, 75.3%, 100.0%]

100 d post-LAMS placement 100% (27/27) 100% (13/13) 100% (40/40)
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Time to radiographic WON resolution of ≤ 3 cm (d) 33.8 ± 19.0 (4.0,100.0) 34.8 ± 11.6 (18.0,51.0) 34.1 ± 16.8 (4.0–100.0)
Recurrence of WON from initial resolution to 6 mo 0.0% (0/22) 0.0% (0/12) 0.0% (0/34)
post-LAMS removal*
Resolution of symptoms and signs of infection,
deteriorating organ function, gastric outlet obstruction,
biliary obstruction, or tube feeding (N = 30)
By time of LAMS removal 66.7% (18/27) 92.3% (12/13) 22 (73.3% of 30)
By 6 mo after LAMS removal† 81.8% (18/22) 91.7% (11/12) 24 (96% of 25)
Incidence of new organ failure from drainage procedure to 3.8% (1/26) 0.0% (0/13) 1 (2.6% of 39)
WON resolution
Change of SF-12 score from baseline to:
At time of LAMS removal‡ 24.6 ± 21.9 (24) 21.7 ± 18.2 (13) 23.6 ± 20.5 (37)
(−26.1,67.2) (−9.4,49.8) (−26.1 to 67.2)
At 6 mo after LAMS removal§ 42.5 ± 27.9 (16) 38.5 ± 18.8 (11) 40.9 ± 24.3 (27)
(−12.5,81.3) (7.8,69.9) (−12.5 to 81.3)
*Excludes 5 patients lost to follow-up, 1 patient who died before 6-month follow-up visit.
†Excludes 4 patients lost to follow-up, 1 patient who died before 6-month follow-up visit.
‡Values from 37 patients, including 5 values below zero: −26.125, −9.375, −4.875, −4.5, and −0.25.
§Values from 27 patients, including 1 value below zero: −12.5.ITT indicates intention to treat; LAMS, lumen-apposing metal stent; WON, walled-off necrosis.

Study Endpoints
The primary efficacy endpoint was the proportion of
patients with radiographic resolution of WON following endo-
scopic management defined as a radiographic decrease of the
WON size to ≤3 cm as demonstrated by CT scan or MRI within
60 days of LAMS placement. This imaging parameter is clin-
ically relevant because larger WON size and presence of ≥30%
solid necrosis predict WON progression and the need for inter-
vention including step-up therapy after endoscopic drainage with
LAMS.9–12 The size criterion is based on the internal (within-
WON) LAMS flange diameter being 24 to 29 mm. Secondary
efficacy endpoints included the technical success of LAMS
placement and removal, procedure duration, time to radio-
graphic resolution, proportion of patients with recurrence of
radiographic WON by 6 months after LAMS removal, reduction
of key WON-related signs or symptoms (ie, signs or symptoms of
infection (fever, leukocytosis, visualization of gas bubbles within
the necrotic tissue on CT imaging, and/or systemic inflammatory
response syndrome/SIRS), deteriorating organ function, gastric
outlet obstruction, biliary obstructive symptoms, or tube feed-
ing), hospitalization status, and change in SF-12 quality of life
score questionnaire from baseline to LAMS removal and base-
line to end of study. The primary safety endpoint was SAEs
related to the LAMS or the procedure, consistent with the ISO
14155 and MEDDEV 2-7/ 3 definitions.
Sample Size Calculation
Sample size was a priori determined by the US FDA given
the regulatory nature of the study to obtain 510(k) clearance of
LAMS treatment for WON with > 30% solid necrosis burden.
Forty patients were needed to assess pre-established efficacy and
safety success criteria, which were based on WON resolution
rates16–22 and associated SAEs17–19,23 documented in published
studies of plastic stents to treat WON. For the primary efficacy
endpoint, the success criterion would be met by a minimum
observed proportion of 67% of patients (n ≥ 27 of 40) who had a
reduction of WON size to ≤3 cm within 60 days after LAMS
placement. For the primary safety endpoint, the success criterion
would be met by a maximum observed rate of 17.5% of patients
(n ≤7 of 40) with LAMS-related or WON debridement proce-
dure-related SAEs.
Statistical Analysis
Baseline characteristics, medical history, outcome
measures, and adverse events were summarized using mean,
median, standard deviation, and range for continuous varia-
bles (eg, age, procedure times), and proportions for categorical
variables (eg, sex, race, organ failure score). All variables were
stratified by hospitalization status at the time of the procedure
as a marker of illness severity. Time to radiographic WON
resolution was plotted using a Kaplan-Meier curve. All anal-
yses were performed using SAS version 9.4 (SAS Institute,
Cary, NC).
RESULTS
Baseline Patient and Procedural Characteristics
Of 146 patients who were screened, 40 (25.3%) were
consecutively enrolled after providing written informed consent
to participate in the study (Fig. 1). The 3 most common reasons
for nonparticipation were prior surgical, interventional radiol-
ogy, or endoscopic treatment of WON (n = 25), imaging or
endosonographic findings suggesting ≤30% necrosis (n = 22), or
pseudocysts (n = 17).
Of the 40 enrolled patients (mean age 54.5 years, mean
BMI 29.2) who underwent LAMS-based WON management,
most were inpatients at the time of their procedure (67.5%, 27/
40), and 14 (35.0%) required parenteral or enteral feeding
(Supplementary Table 1, http://links.lww.com/SLA/D508). At
baseline, the mean time since reported onset of acute pancreatitis
was 91.2 ± 81.0 (range 15–375) days, including 3 patients with
times shorter than 28 days (15, 16, 23 days). The most commonly
identified causes of acute pancreatitis were gallstones (n = 22,

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 Annals of Surgery  Volume 277, Number 5, May 2023 Pancreatic Walled-off Necrosis
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FIGURE 3. WON dimension (cm) during serial assessments until radiographic resolution.

55.0%) and alcohol (n = 4, 10.0%). Nineteen (47.5%) patients had

TABLE 3. LAMS-or Procedure-related Serious Adverse Events at least one sign of infection at baseline; the remainder received the
(N = 40) intervention based on persistent symptoms. The mean baseline
Serious Adverse Event Percent (n/N) SF-12 score was 35.1 ± 19.5 (n = 38; range 0–85.5).
Preprocedure imaging showed that mean WON size was
All LAMS- or procedure-related serious adverse events 7.5 (3/40)
15.0 ± 5.6 cm with mean 53.2% ± 16.7% solid necrosis. Thirty-
Sepsis* 2.5 (1/40)
Vancomycin-resistant enterococcal bacteremia† 2.5 (1/40) nine (97.5%) patients received periprocedural antibiotics
Worsening multifactorial shock† 2.5 (1/40) (Table 1). The LAMS lumen diameter used in the baseline
Upper gastrointestinal bleeding‡ 2.5 (1/40) procedure was 15 mm in 15 (37.5%) and 20 mm in 25 (62.5%)
cases. A plastic stent was placed within the LAMS to reduce the
*Sepsis on Day 2 after LAMS placement, resolved in 39 days; LAMS removed
at Day 59. risk of occlusion in 61.5% (24/ 39) patients in the index proce-
†VRE bacteremia (onset Day 6, resolved in 38 d) and worsening multifactorial dure. No nasocystic drains were placed during the study.
shock (onset Day 22, resolved in 6 d) occurred in the same patient; LAMS removed
at Day 41.
‡Upper gastrointestinal bleeding: friable gastric mucosa in upper body of Technical Success
stomach and large blood clot without active bleeding observed on Day 17. Blood
transfusion required. LAMS removed uneventfully on Day 33. LAMS Placement and WON Drainage
LAMS indicates lumen-apposing metal stent. All LAMS- or procedure-related Technical success was seen in all 41 LAMS (100%)
serious adverse events occurred in inpatients.
placements in 40 patients. One patient received 2 LAMS placed

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 Abu Dayyeh et al
at the index procedure (one with a plastic stent through the
LAMS and one without). The second stent was needed to
maintain a spontaneous WON gastric fistula discovered in a
distal gastric location not conducive for subsequent necrosec-
tomy. The mean duration of the entire procedure including
LAMS placement was 41.2 ± 14.9 (range 17–70) minutes.
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LAMS Removal
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All LAMS were removed successfully without difficulty or
complication. At the time of LAMS removal, the patient with 2
LAMS placed at the index procedure was observed to have one
LAMS in place, but the other LAMS had migrated. The LAMS
that migrated initially had a DPPS placed through its lumen, of
which the LAMS had a complete distal migration and was
expelled from the body. The DPPS was found to have migrated
into the stomach and was retrieved endoscopically. No adverse
events were associated with either migration. At the time of
LAMS removal, 9 patients (22%) underwent placement of two 7
Fr plastic double-pigtail stents to prevent pancreatic fluid col-
lection recurrence in individuals with documented disconnected
pancreatic duct syndrome diagnosed on cross-section imaging or
EUS.24
WON Assessments, Necrosectomies, and Follow-up
A mean of 2.9 ± 1.8 WON assessments (by CT or MRI)
were conducted for each patient. Based on these assessments, a
mean of 2.2 ± 1.8 DEN were performed per patient. The mean
cumulative total (over the duration of the study) necrosectomy
time per patient was 101.6 ± 80.6 minutes. DEN was required
for 36 (90.0%) patients. The 4 patients who did not require
necrosectomy prior to WON resolution all had baseline necrotic
content ≤50%. Two patients subsequently received an additional
LAMS for a secondary access drainage site on Day 3 and Day 11
as access through the initial LAMS was not optimal for DEN
performance (distal in the stomach with looping of the scope).
Two additional patients had their initial LAMS exchanged for a
new LAMS during DEN procedures on Day 27 and Day 44.
All 40 patients (100%) were participating in the study at
the time of LAMS removal, and 34 (85%) participated in the
6-month post LAMS removal study visit. Five patients were lost
to follow-up and 1 patient died of cholangiocarcinoma 138 days
after LAMS removal. Among these 6 patients, the last docu-
mented study visit was at the stent removal visit for 1, and at the
7-day post-stent removal visit for the other 5. No LAMS- or
procedure-related AEs were reported at those visits, but 1 lost-
to-follow-up patient later had 4 unrelated SAEs.
Radiographic Resolution of WON
Among all 40 patients, radiographic WON resolution was
achieved in 39 (97.5%; 95% CI, 86.8%–99.9%) by 60 days after
LAMS placement, surpassing the a priori defined efficacy
threshold of 67% (Fig. 2). There were no recurrent fluid collec-
tions among the 34 patients having a 6-month post-LAMS
removal follow-up (not including 5 patients lost to follow-up and
one who died before the 6-month follow-up visit) (Table 2).
The mean time to radiographic WON resolution was 34.1
± 16.8 days (range 4–100) (Fig. 3). Durations to radiographic
WON resolution were similar by patient status, WON size,
percentage of solid necrosis, LAMS size, or use of DPPS. One
patient failed to meet the primary effectiveness endpoint by
60 days but had resolution of the WON collection by 100 days.
On day 54, this patient underwent CT-guided placement of a
percutaneous drain that was subsequently upsized when the
e1078 | www.annalsofsurgery.com Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.
Annals of Surgery  Volume 277, Number 5, May 2023
collection failed to resolve. At day 61, this patient underwent
laparoscopic-assisted pancreatic debridement, achieved WON
resolution on day 100, and underwent endoscopic LAMS
removal on day 125 without difficulty.
Reduction of Key WON-related Signs or Symptoms
All patients had at least 1 symptom at baseline (Supple-
mentary Table 1, http://links.lww.com/SLA/D508). Thirty
patients had 1 or more of the following severe WON-related
symptoms at baseline: signs or symptoms of infection, deterio-
rating organ function, gastric outlet obstruction, biliary
obstructive symptoms, or symptoms requiring tube feeding. The
remaining 10 patients had at least one of the following non-
specific symptoms at baseline: abdominal pain, weight loss,
chronic nausea, or failure to thrive.
At LAMS removal, 9 patients reported at least 1 of the 4
severe conditions, including 8 with and 1 without at least 1 severe
symptom at baseline. Among 34 patients with 6-month post-
LAMS removal data, 1 patient reported at least 1 (feeding tube),
and 33 patients showed none, of the 4 severe conditions.
Regarding specific conditions, of 19 patients who had 1 or
more signs or symptoms of infection at baseline, 14 (73.7%) had
no signs of infection at the 6-month post-LAMS removal, 1
(5.3%) patient died, and 4 (21.1%) were lost to follow-up after
WON resolution and LAMS removal before the 6-month visit.
Two patients
(both inpatients at time of procedure) developed SIRS
during study follow-up but reported no WON symptoms at the
6-month visit. Of 10 patients who reported gastric outlet
obstruction at baseline, 9 (90.0%) did not report this condition at
the 6-month post-LAMS removal visit and 1 (10.0%) was lost to
follow-up. Of 4 patients who reported biliary obstruction
symptoms at baseline, none had this condition at the 6-month
post-LAMS removal visit. Of 12 patients who reported tube
feeding at baseline, 11 (91.7%) did not require supplemental
feeding at the 6-month post-LAMS removal visit and 1 (8.3%)
was lost to follow-up.
Hospitalization Status
Of 27 patients who were inpatients at the time of their
procedure, 6 remained inpatients, 19 were discharged from the
hospital, 1 was discharged and readmitted to the hospital, and 1
was discharged, required interval hospitalization and was again
discharged from the hospital by the time of LAMS removal. Of
13 patients who were outpatients at baseline, 11 remained out-
patients, and 2 required hospitalization and then were discharged
before the time of LAMS removal. In total, 29 (72.5%) of
patients were hospitalized at some point during the study.
Change in Self-reported Quality of Life
The mean improvement in score from baseline to LAMS
removal was 23.6 ± 20.5 (n = 37), with the mean improvement in
score from baseline to end of the study being 40.9 ± 24.3 (n = 27).
LAMS- or Procedure-related Serious Adverse Events
LAMS- or procedure-related SAEs are summarized in
Table 3. In the 2 cases of sepsis and bacteremia, a coaxial plastic
stent was not placed. In the patient with upper gastrointestinal
bleeding, the last preprocedure scan performed 2 days before
LAMS placement did not show evidence of a pseudoaneurysm.
This patient did not have a
plastic stent placed within the LAMS at the index proce-
dure. The patient’s LAMS was removed uneventfully on day 33
 Annals of Surgery  Volume 277, Number 5, May 2023
followed by uneventful follow-up at 6 months post-LAMS
removal.
In addition, 1 patient died from cholangiocarcinoma
138 days after LAMS removal. This death was determined to be
unrelated to the LAMS or LAMS placement or removal.
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DISCUSSION
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In this prospective multicenter clinical trial, endoscopists
using protocolized LAMS-based endoscopic management of
WON with >30% solid necrosis (approximately half with infec-
tion) achieved radiographic WON resolution by 60 days in 97.5%
of study participants with resolution of infectious complications or
WON-related symptoms. The mean time to WON resolution was
34 days with no treatment-related mortality, new onset organ
failure, or collection recurrence at 6 months follow-up post-LAMS
removal. There was a low rate of LAMS-related SAEs with no
procedure-related deaths or new organ failure. Significant
improvements in self– reported quality of life scores persisted by
6 months after completion of treatment.
The incidence of acute pancreatitis has increased in the US
over the past 2 decades.25,26 The high morbidity and mortality
and prolonged hospitalization for patients with pancreatitis who
develop WON offer compelling reasons for development of more
effective, safer, and less costly endoscopic treatment approaches
for this condition.27 An endoscopic step-up approach has
emerged as the preferred first-line approach given lower inci-
dence of pancreatic fistula formation.7,28-31 LAMS are increas-
ingly utilized for WON management as they facilitate drainage
of solid necrosis and enable direct through-the-stent efficient
endoscopic debridement.
Our findings and therapeutic approach represent a shift in
the management of WON suggesting that for collections with
>30% necrosis, an early protocolized reimaging and endoscopic
intervention approach, coupled with prompt LAMS removal for
resolved collections, may be favored over previous approaches.
Most (90%) of our cohort required DEN, reflecting inclusion of
larger WONs with significantly higher solid necrosis compared
with previous studies. Per regulatory design, most exclusions
from our study were based on WON with minimal solid debris or
pseudocysts, which differed from previous investigations of step-
up therapy.32,33 High response rate to drainage alone may reflect
minimal solid debris, regardless of infection. Indeed, in a large
recent cohort study, the need for step-up therapy and DEN was
predicted by baseline collection size, distribution, and percent
solid component, not by indication for therapy or infection,
which corroborates our results and calls for better stratification
of WON at baseline for personalized and standardized treatment
algorithms.9 However, randomized trials are necessary to con-
firm these findings.
Our study had several limitations. This was a single-arm
study conducted by expert pancreatic-focused endoscopists at
large university medical centers. The favorable results might not
be replicable at centers with lower procedural volumes, less
experience, or with fewer specialty resources. Central imaging
review was not available. We used a clinical definition of pre-
sumed infection, that is, fever, leukocytosis, visualization of gas
bubbles within the necrotic tissue on CT imaging, and/or SIRS.
Culture data were not available to confirm the presence of
infection at the index procedure. Although the protocol specified
that pancreatitis severity should be reported according to the
2012 Revised Atlanta Classification,2 only 5 of 21 patients
identified as “severe” were reported to have organ failure or a
nonzero organ failure score; this suggests that most of patients
Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.
Pancreatic Walled-off Necrosis
actually had moderate pancreatitis including a local complica-
tion of WON. An estimated 19 (47.5%) patients had at least 1
sign of infection and 13 (32.5%) were treated as outpatients at
the index procedure (2 of whom were hospitalized during follow-
up); therefore, our outcomes are derived from a cohort with less
infected necrosis and less morbidity relative to findings from 3
randomized controlled trials6–8 comparing endoscopic to surgi-
cal treatment of infected WON. This may have contributed to
the improved outcomes seen in this study. However, this study
sequentially recruited all patients who presented with pancreatic
WON at these specialized centers and met the inclusion criteria,
thus representing a generaliz- able cohort of patients encoun-
tered in clinical practice. Finally, the 6- month follow-up period
after LAMS removal may have been too short to identify WON
recurrences due to disconnected pancreatic duct syndrome.
CONCLUSIONS
Expert endoscopists using LAMS for WON drainage,
performing DEN, and following a protocolized algorithm ach-
ieved a very high rate of WON resolution, few LAMS-related
SAEs and improved self-rated quality of life maintained to
6 months post- LAMS removal.
ACKNOWLEDGMENT
Margaret Gourlay, MD, MPH, a Boston Scientific Corpo-
ration employee, provided writing assistance.
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