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Gastroenterology 2022;163:1107–1114
CLINICAL PRACTICE UPDATE
AGA Clinical Practice Update on the Endoscopic Approach
to Recurrent Acute and Chronic Pancreatitis: Expert Review
Daniel S. Strand,1,* Ryan J. Law,2,* Dennis Yang,3 and B. Joseph Elmunzer4
1Division of Gastroenterology and Hepatology, University of Virginia Health System, Charlottesville, Virginia; 2Department of
Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota; 3Center for Interventional Endoscopy, AdventHealth,
Orlando, Florida; and 4Division of Gastroenterology and Hepatology, Medical University of South Carolina, Charleston, South
Carolina
*Authors share co-first authorship.
Abbreviations used in this paper: AP, acute pancreatitis; CP, chronic
pancreatitis; CPB, celiac plexus block; ERCP, endoscopic retrograde
cholangiopancreatography; ESWL, extracorporeal shockwave lithotripsy;
EUS, endoscopic ultrasound; FCSEMS, fully covered self-expanding metal
stents; MPD, main pancreatic duct; MRCP, magnetic resonance chol-
angiopancreatography; MRI, magnetic resonance imaging; PD, pancreas
divisum; RAP, recurrent acute pancreatitis.
Most current article
© 2022 by the AGA Institute.
0016-5085/$36.00
https://doi.org/10.1053/j.gastro.2022.07.079
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DESCRIPTION: The purpose of this American Gastroentero-
logical Association (AGA) Clinical Practice Update Expert Re-
view is to provide practical, evidence-based guidance to
clinicians regarding the role of endoscopy for recurrent acute
and chronic pancreatitis. METHODS: This expert review was
commissioned and approved by the AGA Institute Clinical
Practice Updates Committee and the AGA Governing Board to
provide guidance on a topic of clinical importance to the AGA
membership, underwent internal peer review by the Clinical
Practice Updates Committee (CPUC), and external peer review
through standard procedures of Gastroenterology. This review
is framed around the 8 best practice advice points agreed upon
by the authors, based on the results of randomized controlled
trials, observational studies, systematic reviews and meta-
analyses, as well expert consensus in this field.
BEST PRACTICE ADVICE 1: After an unrevealing initial eval-
uation, endoscopic ultrasound is the preferred diagnostic test
for unexplained acute and recurrent pancreatitis. Magnetic
resonance imaging with contrast and cholangiopancreatog-
raphy is a reasonable complementary or alternative test to
endoscopic ultrasound, based on local expertise and availabil-
ity. BEST PRACTICE ADVICE 2: The role of endoscopic retro-
grade cholangiopancreatography (ERCP) for reducing the
frequency of acute pancreatitis episodes in patients with
pancreas divisum is controversial, but minor papilla endo-
therapy may be considered, particularly for those with objec-
tive signs of outflow obstruction, such as a dilated dorsal
pancreatic duct and/or santorinicele. There is no role for ERCP
to treat pain alone in patients with pancreas divisum. BEST
PRACTICE ADVICE 3: The role of ERCP for reducing the fre-
quency of pancreatitis episodes in patients with unexplained
recurrent acute pancreatitis and standard pancreatic ductal
anatomy is controversial and should only be considered after a
comprehensive discussion of the uncertain benefits and
potentially severe procedure-related adverse events. When
pursued, ERCP with biliary sphincterotomy alone may be
preferable to dual sphincterotomy. BEST PRACTICE ADVICE 4:
Surgical intervention should be considered over endoscopic
therapy for long-term treatment of patients with painful
obstructive chronic pancreatitis. Endoscopic intervention is a
reasonable alternative to surgery for suboptimal operative
candidates or those who favor a less invasive approach,
assuming they are clearly informed that the best practice advice
primarily favors surgery. BEST PRACTICE ADVICE 5: When
ERCP is pursued, small (�5mm) main pancreatic duct stones
BEST PRACTICE ADVICE STATEMENTS
can be treated with pancreatography and conventional stone
extraction maneuvers. For larger stones, extracorporeal
shockwave lithotripsy and/or pancreatoscopy with intraductal
lithotripsy may be required. BEST PRACTICE ADVICE 6: When
ERCP is pursued, prolonged stent therapy (6–12 months) is
effective for treating symptoms and remodeling main pancre-
atic duct strictures. The preferred approach is to place and
sequentially add multiple plastic stents in parallel (upsizing);
emerging evidence suggests that fully covered self-expanding
metal stents may have a role for this indication, but addi-
tional research is necessary. BEST PRACTICE ADVICE 7: ERCP
with stent insertion is the preferred treatment for benign
biliary stricture due to chronic pancreatitis. FCSEMS placement
is favored over multiple plastic stents whenever feasible, given
similar efficacy but significantly reduced need for stent ex-
change procedures during the treatment course. BEST
PRACTICE ADVICE 8: Celiac plexus block should not be
routinely performed for the management of pain due to chronic
pancreatitis. The decision to proceed with celiac plexus block in
selected patients with debilitating pain in whom other thera-
peutic measures have failed can be considered on a case-
by-case basis, but only after discussion of the unclear
outcomes of this intervention and its procedural risks.
cute pancreatitis (AP) remains the leading cause of
1
Ainpatient care among gastrointestinal conditions.
After recovery from an index episode, 10%–30% of pa-
tients will develop recurrent acute pancreatitis (RAP),2,3
defined as 2 or more distinct episodes of AP with com-
plete interceding resolution, separated by at least 3 months.
Approximately 35% of patients with RAP will progress to
chronic pancreatitis (CP)2,3—an irreversible fibroin-
flammatory condition resulting in varying degrees of pain
and exocrine and endocrine insufficiency. Other patients
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https://doi.org/10.1053/j.gastro.2022.07.079
Figure 1. Interventions
aimed to better evaluate,
mitigate the progression
of, and treat symptoms
related to AP and CP.
1108 Strand et al Gastroenterology Vol. 163, No. 4
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will develop CP without antecedent attacks of AP. Both RAP
and CP are associated with significant morbidity and mor-
tality, including high levels of health care utilization and
disability.4,5 Interventions aimed to better evaluate, mitigate
the progression of, and treat symptoms related to AP and CP
are critical to improve patients’ quality of life and other
long-term outcomes (Figure 1). The intent of this document
is to offer practical guidance pertaining to endoscopy in
patients with RAP and CP.
Acute Pancreatitis
Evaluation of Unexplained Acute and Recurrent
Pancreatitis
Despite routine efforts to identify a cause, which should
include a comprehensive personal and family history,
physical examination, medications review, laboratory
testing (eg, liver biochemistries, triglycerides, and calcium),
and noninvasive imaging, the etiology of AP remains unex-
plained in 16%–27% of all cases.6,7 Endoscopic ultrasound
(EUS) has become the most important diagnostic tool for the
evaluation of unexplained AP,8,9 uncovering a potential eti-
ology in 29%–88% of patients.10–13 The variable diagnostic
yield of EUS can be attributed to several factors, including
patient demographic characteristics, the tempo and pattern
of RAP, and the a priori likelihood of a biliary etiology on the
basis of liver biochemistries and the presence of a gall-
bladder.11 The most common etiology for AP identified at
EUS is indeed occult biliary lithiasis.11,12 Importantly, occult
ampullary or pancreatobiliary malignancy may be observed
in up to 5% of patients after a single episode of unexplained
AP and in up to 12% of those with RAP.11
Based on available evidence, magnetic resonance imag-
ing (MRI) with contrast and cholangiopancreatography
(MRCP) are considered to be complementary or alternative
tests toEUS in the evaluation of unexplained AP.8,11,12 A
recent meta-analysis comparing these 2 modalities suggests
that EUS is more likely than MRI to provide a probable
cause of AP (odds ratio, 3.79). This finding is driven pri-
marily by its sensitivity for occult biliary stones12 and is
consistent with the existing literature that includes blinded,
prospective comparisons.14–17 Nonetheless, MRI can be
particularly helpful in identifying potential pancreatic ductal
etiologies of AP, including the diagnosis of anatomical var-
iants, such as pancreas divisum (PD) or anomalous pan-
creaticobiliary union. Although secretin-enhanced MRCP has
been shown to improve diagnostic yield compared with
standard MRI/MRCP, its clinical utility is currently limited
October 2022 AGA Clinical Practice Update: Endoscopy for RAP and CP 1109
by availability, logistics of secretin administration, and
variability in dynamic secretin-enhanced MRCP acquisition
and interpretation.15,16,18
Overall, we believe EUS is the preferred initial modality
in the evaluation of patients with unexplained AP and RAP.
Although the optimal timing for EUS has not been concretely
defined, most experts advise a short delay (ie, 2–6 weeks)
after resolution of AP, as persistent inflammatory changes
may hinder endosonographic evaluation of subtle lesions
and underlying CP. Contrasted MRI and MRCP can be
complementary, particularly if the EUS examination is
unrevealing. It also remains a reasonable alternative test
when expertise in EUS is not available.
Best Practice Advice 1: After an unrevealing initial
evaluation, EUS is the preferred diagnostic test for un-
explained acute and recurrent pancreatitis. MRI/MRCP
is a reasonable complementary or alternative test to
EUS, based on local expertise and availability.
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Endoscopic Retrograde Cholangiopancreatography
for Recurrent Acute Pancreatitis in Patients With
Pancreas Divisum
PD is the result of failure of fusion of the dorsal and
ventral pancreatic ductal systems during embryogenesis,
leading to dominant pancreatic duct drainage through the
minor papilla. PD is the most common congenital pancreatic
anomaly, occurring in approximately 6%–10% of individu-
als.19–21 The large majority of patients with PD are asymp-
tomatic; hence, there is considerable controversy as to the
clinical significance of PD in pancreatic disease. Nonetheless,
it has been proposed that a subset of patients with PD may
have impaired drainage of pancreatic secretions through the
dorsal-dominant system, potentially resulting in increased
intraductal pressures, which may precipitate RAP.22,23
Conceptually, endoscopic therapy for symptomatic PD
aims to relieve outflow obstruction by enlarging the minor
papilla. This can be achieved during ERCP through minor
papilla sphincterotomy, balloon dilation, stent placement, or
some combination thereof.
High-quality studies supporting endoscopic therapy in
patients with PD and RAP are lacking. In aggregate, data
from retrospective uncontrolled studies suggest that
endoscopic intervention may reduce or eliminate episodes
of RAP in up to 60%–80% of patients.24 However, these
results should be interpreted with caution, given the
observational nature of the data, heterogeneity in patient
populations, differences in outcome definitions, varied
endoscopic interventions, and short follow-up. There has
been only 1 randomized trial evaluating the effect of
minor papilla therapy in patients with RAP and PD. In
this study of only 19 patients, minor papilla stenting was
associated with a significant decrease in future episodes
of AP compared with controls (10% vs 67%; Pof impaired quality of life in patients with CP.4 Although
pain is often multifactorial, a subset of patients with CP are
thought to experience symptoms due to intraductal hyper-
tension from an obstructed pancreatic duct.33,34 In such
patients, surgical or endoscopic drainage to reduce
pancreatic duct pressures may result in durable symptom
improvement. Decompression is almost never of value or
indicated in asymptomatic patients, although some experts
argue in favor of intervention in the case of a younger
asymptomatic patient with unifocal obstruction that is
downstream of substantial viable (nonatrophic) paren-
chyma.35 In these cases, the rationale for drainage is to slow
the progression of disease, including the loss of islet cells.
Three randomized trials suggested that early surgical
intervention is superior to endoscopic therapy for pain relief
in patients with obstructive CP.36–38 The recent ESCAPE
trial, a Dutch multicenter randomized trial of 88 patients
with a dilated main pancreatic duct (MPD) demonstrated
higher complete or partial pain relief (58% vs 39%) in the
early surgery group compared with the endotherapy group
during 18 months of follow-up.38 These results are
congruent with those of 2 prior randomized controlled trials
from the Czech Republic and the Netherlands.36,37 Although
these studies have limitations that are inherent to studying
this challenging question, the overall data support early
surgery over endoscopic decompression for the treatment
of pain in obstructive CP. It is also important for patients to
consider that surgery is a one-time intervention, whereas
endoscopic therapy typically requires serial ERCPs over the
course of up to 12 months. Despite these considerations, it
has remained customary in clinical practice for patients to
first be referred for endoscopic treatment, given its less
invasive and ambulatory nature, and the perception of
lower risk compared with surgery. Furthermore, several
clinical guidelines favor endoscopic therapy as the initial
intervention for symptomatic pancreatic duct obstruction
related to CP.39–41 We agree that endoscopy is a reasonable
alternative to surgery in patients who are suboptimal
operative candidates or those favoring a less invasive
approach, but we suggest that endoscopists highlight the
evidence favoring surgery and the logistical challenges
associated with the need for repeat ERCPs. Given its
complexity, shared decision-making should ideally involve
all care providers (eg, surgeon, endoscopist, gastroenterol-
ogist, primary care physician, and psychologist) as to pro-
vide patients with a balanced presentation of the evidence
to make a truly informed decision.
Best Practice Advice 4: Surgical intervention should be
considered over endoscopic therapy for long-term treat-
ment of patients with painful obstructive CP. Endoscopic
intervention is a reasonable alternative to surgery for
suboptimal operative candidates or thosewho favor a less
invasive approach, assuming they are clearly informed
that the best practice advice primarily favors surgery.
Endoscopic RetrogradeCholangiopancreatography
for Pancreatic Duct Stones
Pancreatic duct stones can develop in approximately
60% of patients with CP, more commonly among men and
those with heavy alcohol (>80 g/d) and tobacco (>20 cig-
arettes/d) use.42 As above, stones that result in symptom-
atic obstruction require therapy, which will depend largely
on the size and location of the stone. Conventional ERCP
with standard stone extraction techniques (eg, sphincter-
otomy, dilation, and balloon/basket retrieval) is often suf-
ficient for small stones (�5 mm). For stones >5 mm,
existing data support the use of extracorporeal shock wave
lithotripsy (ESWL) for fragmentation with or without sub-
sequent ERCP.43 ESWL is highly effective at stone frag-
mentation (>90%)44 and subsequent complete clearance of
the pancreatic duct by ERCP is achievable in more than two-
thirds of patients. More than one-half of patients treated in
this way remain pain-free over a 2-year interval, and up to
89% report significant improvements in quality of life.45
However, ESWL for pancreaticolithiasis is not widely avail-
able in the United States, limiting the generalizability of this
approach.
Pancreatoscopy-directed lithotripsy (electrohydraulic or
laser) is a potential alternative to ESWL for stones that are
refractory to conventional ERCP and/or when ESWL is not
available. Reported success rates of intraductal therapy for
MPD calculi have varied significantly (47%–89%).46,47
Lower success rates are associated with technical diffi-
culty in achieving access to the intended target due to
pancreatic duct strictures, multiple stones, and/or upstream
location. A recent meta-analysis suggested a high technical
(88%) success rate for pancreatoscopy-directed lithotripsy,
with an acceptable rate of adverse events (12%),48 although
patients with very large stones that would normally be sent
for ESWL or surgical treatment are unlikely to have been
included in the incorporated studies. Recent single-center
data suggest that intraductal therapy may require fewer
overall procedures and less aggregate procedure time
compared with ESWL plus ERCP49; however, in our expe-
rience, ESWL and pancreatoscopy-directed lithotripsy are
often complementary in the management of large and/or
complex stones.
October 2022 AGA Clinical Practice Update: Endoscopy for RAP and CP 1111
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Best Practice Advice 5: When ERCP is pursued, small
(£5 mm) MPD stones can be treated with pancreatog-
raphy and conventional stone extraction maneuvers.
For larger stones, ESWL and/or pancreatoscopy with
intraductal lithotripsy may be required.
Endoscopic RetrogradeCholangiopancreatography
for Pancreatic Duct Strictures
Benign fibro-inflammatory strictures of the pancreatic
duct are a common consequence of CP and may arise in
isolation or in combination with pancreaticolithiasis. The
goals of endoscopic therapy for MPD strictures are to
decompress the distended duct for immediate pain relief
and to achieve enduring stricture remodeling and patency
after long-term stent dwell. In this context, endotherapy
involves stricture dilation and long-term stent placement
with sequential upsizing, as necessary, similar to man-
agement of CP-related biliary strictures. Abdominal pain
can be relieved in up to 85% of CP patients who undergo
ERCP with stent placement across an MPD stricture.50
During subsequent sessions, MPD strictures can be
effectively remodeled by either upsizing the caliber of the
stent or placing multiple stents in parallel.50,51 For many
patients, durable stricture remodeling using plastic stents
requires 6–12 months of incremental stent replacement
and upsizing at prespecified intervals.52 It should be
noted that available data are derived from observational
studies with a high risk of bias and, therefore, additional
rigorous research is necessary to refine our estimates of
benefit.
The off-label use of fully covered self-expandable
metal stents (FCSEMS) for treatment of CP-related
MPD strictures has been described. A recent system-
atic review and meta-analysis comparing outcomes of
FCSEMS (192 patients) and multiple plastic stents (106
patients) for the treatment of MPD strictures noted no
differences in pain improvement (88% vs 89%) or
stricture recurrence (8% vs 11%).51 Patients treated
with FCSEMS required fewer ERCPs, but their adverse
event rate was significantly higher (39% vs 14%), which
raises questions about the overall role of FCSEMS in this
clinical context. Adverse events that have been associ-
ated with SEMS in the PD include stent migration, bile
duct obstruction, difficulty with removal, and de novo
PD stricture formation.
Best Practice Advice 6: When ERCP is pursued,
prolonged stent therapy (6–12 months) is effective for
treating symptoms and remodeling MPD strictures.
The preferred approach is to place and sequentially
add multiple plastic stents in parallel (upsizing);emerging evidence suggests that FCSEMS may have a
role for this indication, but additional research is
necessary.
Endoscopic RetrogradeCholangiopancreatography
for Bile Duct Strictures
Benign biliary strictures with obstruction occur in
approximately 15% of patients with advanced CP.53 When
the obstruction is not transient, ERCP for biliary decom-
pression is advised.39 Traditional therapy includes pro-
gressive placement of an increasing number of plastic stents
across the stricture for up to 1 year in order to promote
remodeling and long-term patency.54 While clinically suc-
cessful in up to 90% of patients, this approach entails
several ERCP sessions (ie, every 10–12 weeks), leading to
substantial resource utilization and compounded proce-
dural risk.55 As such, the use of FCSEMS for CP-related
biliary strictures has continued to gain traction.55–57 Two
recent methodologically rigorous randomized trials
comparing FCSEMS to multiple plastic stents for benign
biliary strictures showed similar treatment success rates
and safety profiles, but significantly fewer procedures
associated with the use of FCSEMS.55,56 It is important to
consider that 1 of the trials excluded patients with a gall-
bladder, in whom the cystic takeoff could not be avoided by
the covered stent and the other study (enrolling only pa-
tients with CP) observed a numerically larger number of
cholecystitis cases in the FCSEMS group. Observational data
also suggest the possibility of increased cholecystitis asso-
ciated with FCSEMS, presumably due to cystic duct
obstruction.58 Given the potential risk of cholecystitis, and
considering that multiple plastic stent therapy is not inferior
in terms of stricture resolution, it remains reasonable to
avoid FCSEMS in patients with gallbladder in situ when the
stent will cover the cystic duct orifice. Based on available
evidence, stent therapy should be continued for 6–12
months, depending on stricture severity, stent type, and
response.56,57
Best Practice Advice 7: ERCP with stent insertion is
the preferred treatment for benign biliary stricture due
to CP. FCSEMS placement is favored over multiple
plastic stents whenever feasible, given similar efficacy
but significantly reduced need for stent exchange pro-
cedures during the treatment course.
Endoscopic Ultrasound–Guided Celiac Plexus
Block for Pain Management in Chronic
Pancreatitis
Long-term pain management for CP remains a formi-
dable challenge, especially in patients with nonobstructive
(ie, small duct) disease. The celiac plexus is a network of
interconnected neural fibers surrounding the celiac artery
as it branches from the aorta. The celiac plexus transmits
visceral sensory inputs (including pain signals) from most of
the upper abdominal organs, including the pancreas. EUS-
guided CPB aims to deliver an injectable compound (local
anesthetic plus corticosteroid) to interrupt neural signaling
in response to intra-abdominal pain. Although CPB is occa-
sionally offered to patients with CP who have debilitating
pain that substantially degrades their quality of life, robust
data supporting the benefit of CPB are lacking. Available
observational studies suggest that pain relief may be ach-
ieved in 50%–60% of patients with a duration of benefit of 6
months or less,59–61 although the overall quality of this ev-
idence is weak and should be interpreted with caution,
given substantial methodological limitations in the existing
1112 Strand et al Gastroenterology Vol. 163, No. 4
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studies on CPB, including a lack of placebo-control, short-
term follow-up, and inconsistent definitions of interventions
and outcomes. Almost all patients will require additional
analgesics after CPB. The role of serial CPB is even less well
understood, but may be considered in select patients with
demonstrated benefit.62 Adverse events of CPB should also
be contextualized to assess the risk to benefit ratio. Diarrhea
and orthostatic hypotension are most common.63,64 Major
adverse events (eg, abscess formation, intravascular injec-
tion, and paralysis) occur inetiological diagnosis of “idiopathic” acute pancrea-
titis. Pancreas 2011;40:289–294.
17. Mariani A, Arcidiacono PG, Curioni S, et al. Diagnostic
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18. SwenssonJ,ZaheerA,ConwellD,etal.Secretin-enhanced
MRCP: howandwhy - AJRExpert Panel Narrative Review.
AJR Am J Roentgenol 2021;216:1139–1149.
19. Bülow R, Simon P, Thiel R, et al. Anatomic variants of the
pancreatic duct and their clinical relevance: an MR-
guided study in the general population. Eur Radiol
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20. Delhaye M, Engelholm L, Cremer M. Pancreas divisum:
congenital anatomic variant or anomaly? Contribution of
endoscopic retrograde dorsal pancreatography.
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21. Bertin C, Pelletier A-L, Vullierm MP, et al. Pancreas
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Received April 27, 2022. Accepted July 1, 2022.
Correspondence
Address correspondence to: Dennis Yang, MD, Center for Interventional
Endoscopy, AdventHealth Orlando, 601 E. Rollins Street, Orlando, Florida
32803. e-mail: dennis.yang.md@adventhealth.com.
Author Contributions
All authors contributed to the conception of the manuscript,the interpretation
of the data, critical revision and final approval of the manuscript.
Conflicts of interest
These authors disclose the following: Dr Law: financial relationship with
Olympus America, ConMed, and Medtronic. Dr Yang: renumeration from
Olympus America, Fujifilm, Apollo Endosurgery, Inc, and Medtronic. Dr Yang
also serves as a member of the Gastrointestinal Endoscopy Editorial Board,
and served as a consultant/received a grant from Microtech. The remaining
authors disclose no conflicts.
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mailto:dennis.yang.md@adventhealth.com
	AGA Clinical Practice Update on the Endoscopic Approach to Recurrent Acute and Chronic Pancreatitis: Expert Review
	Acute Pancreatitis
	Evaluation of Unexplained Acute and Recurrent Pancreatitis
	Endoscopic Retrograde Cholangiopancreatography for Recurrent Acute Pancreatitis in Patients With Pancreas Divisum
	Endoscopic Retrograde Cholangiopancreatography for Recurrent Acute Pancreatitis in Patients With Standard Pancreatic Duct A ...
	Chronic Pancreatitis
	Surgery vs Endoscopic Retrograde Cholangiopancreatography for Painful Obstructive Chronic Pancreatitis
	Endoscopic Retrograde Cholangiopancreatography for Pancreatic Duct Stones
	Endoscopic Retrograde Cholangiopancreatography for Pancreatic Duct Strictures
	Endoscopic Retrograde Cholangiopancreatography for Bile Duct Strictures
	Endoscopic Ultrasound–Guided Celiac Plexus Block for Pain Management in Chronic Pancreatitis
	Conclusions
	References