The role of endoscopy in patients with chronic pancreatitis GUIDELINE

GUIDELINE
The role of endoscopy in patients with chronic pancreatitis
This article is one of a series of statements discussing
the use of gastrointestinal endoscopy in common clinical
situations. The Standards of Practice Committee of the
American Society for Gastrointestinal Endoscopy prepared this text. In preparing this guideline, a MEDLINE
literature search was performed, and additional references were obtained from the bibliographies of the identified articles and from recommendations of expert
consultants. When little or no data exist from welldesigned prospective trials, emphasis is given to results
from large series and reports from recognized experts.
Guidelines for appropriate use of endoscopy are based
on a critical review of the available data and expert
consensus. Further controlled clinical studies are needed
to clarify aspects of this statement, and revision may be
necessary as new data appear. Clinical consideration
may justify a course of action at variance to these
recommendations.
atic duct (PD) or the common bile duct. Endoscopic management should be considered as one management
option along with medical, percutaneous, and surgical
treatments. This guideline will review the role of endoscopy in the management of CP.
ENDOSCOPIC DIAGNOSIS OF CP
Copyright ª 2006 by the American Society for Gastrointestinal Endoscopy
0016-5107/$32.00
doi:10.1016/j.gie.2006.02.003
Although radiologic means to assess patients for CP exist in the form of computed tomographic (CT) scans and
magnetic resonance imaging (MRI) with or without magnetic resonance cholangiopancreatography (MRCP), the
principal endoscopic means of making this assessment include endoscopic retrograde cholangiopancreatography
(ERCP) and endoscopic ultrasonography (EUS). Both
ERCP and EUS can establish the diagnosis of CP. ERCP allows detection of PD changes including ductal dilation,
strictures, abnormal side branches, communicating pseudocysts, PD stones, and PD leaks. ERCP is highly effective
at visualizing these ductal and duct-related findings, with
a sensitivity for the diagnosis of CP of 71% to 93% and
a specificity of 89% to 100%. The Cambridge Classification,
which assesses the main PD, side branches, and intraductal abnormalities, is a widely accepted system for scoring
ductal findings seen on ERCP.3 Unfortunately, pancreatography is imperfect and care should be taken not to overinterpret minor findings seen on ERCP.4 Conversely,
ERCP may not detect changes of less advanced CP. When
the diagnosis of CP is sought, ERCP should be reserved
for patients in whom the diagnosis is still unclear after
noninvasive pancreatic function testing or other noninvasive (CT, MRI) or less invasive (EUS) imaging studies have
been performed.5
Although ERCP can be used to obtain information
about ductal anatomy to define the levels and degree of
obstruction and the presence of strictures and stones, it
does not provide information regarding the surrounding
pancreatic parenchyma. EUS can provide high-resolution
images of both the ductal structures and the parenchyma.6 EUS allows visualization of parenchymal changes
such as alternating hyperechoic and hypoechoic regions
(suggesting increased lobularity), hyperechogenic foci
and strands, focal areas of hypoechogenic tissue, and
the presence of cysts. Ductal changes seen at EUS include
hyperechogenic duct walls, dilation or irregularity of the
main PD, PD stones, and visible side branches.7 The
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Volume 63, No. 7 : 2006 GASTROINTESTINAL ENDOSCOPY 933
INTRODUCTION
Chronic pancreatitis (CP) is an inflammatory process
characterized by destruction of pancreatic parenchyma
and ductal structures with formation of fibrosis. Pain is
the predominant symptom of CP and its origin is multifactorial.1 Treatment is directed toward control of symptoms
and management of the structural complications. Medical
therapies such as abstinence from alcohol, dietary alterations, analgesics, oral enzyme supplements, and somatostatin analogs are variably effective in relieving pain. In
patients for whom medical management fails, surgical
and endoscopic options are available.
Endoscopic therapy for CP was introduced more than
a decade ago. Endoscopic therapy may reduce or eliminate the need for surgical procedures, may serve as
a bridge to surgery in poor operative candidates, and
can predict the response to surgical therapy.2 If endoscopic therapy is unsuccessful, surgical therapy is still a potential option for most patients.
In general, the aim of endoscopic therapy in patients
with CP is to alleviate outflow obstruction of the pancre-
The role of endoscopy in patients with chronic pancreatitis
accuracy of EUS to diagnose CP increases as more of these
distinct abnormalities are identified, and EUS may also
predict the severity of the disease.8 There is good interobserver agreement in the diagnosis of CP by EUS, and EUS
may detect early CP in a reliable manner compared with
ERCP.9,10 Although EUS-guided tissue acquisition may allow the histologic diagnosis of CP, it is not recommended
for routine use.11,12 It may be helpful, however, in diagnosing autoimmune pancreatitis.13,14
a pancreatic duct stricture is undertaken, and appropriate
tissue sampling should be obtained.24 Physicians should
have a low threshold to perform EUS to more closely examine the pancreatic parenchyma, with fine-needle aspiration of any areas felt to be suspicious for possible
malignancy. Obtaining serum CA 19-9 levels may be helpful in patients considered to harbor a malignancy, although levels can be elevated in patients with chronic
pancreatitis in the absence of cancer.
PD STRICTURES
PANCREATIC DUCT STONES
Benign strictures of the main PD are generally due to
inflammation or fibrosis around the main PD. Because
ductal obstruction may lead to pain or acute pancreatitis
superimposed on CP, endoscopic therapy with balloon dilation or PD stents for the treatment of dominant PD strictures has been evaluated. Stricture dilation may be
required to facilitate stent placement or stone removal.
Data regarding the role of endoscopic therapy in treating main PD strictures are inconsistent, and studies addressing this role are heterogeneous. Some authors have
reported high success rates (75% to 94%) in treating
pain by stenting of PD strictures,15-19 although a recent
well-designed study was not able to duplicate these results.20 In addition, although some authors have correlated clinical improvement to a decrease in the diameter
of the main PD upstream to the stent,15,16 others have
not.20 Pancreatic stents are prone to occlusion and patients undergoing endoscopic therapy for PD strictures
may require frequent stent exchanges. Symptomatic improvement may persist after pancreatic stent removal despite persistence of the stricture.17,18 These data suggest
that resolution of the stricture is not a prerequisite for
symptomatic improvement. Confounding the literature
on PD stent therapy are other therapies performed at
the time of stent placement (eg, pancreatic sphincterotomy, pancreatic stone removal) and the tendency of the
CP pain to wax and wane and decrease with time as deterioration of pancreas function occurs.21 The optimum duration of stent placement, stent number and diameter, and
degree of balloon dilation are not known.
Complications related directly to endoscopic therapy of
PD strictures include pain, pancreatitis, stent occlusion,
proximal or distal stent migration, duodenal erosions,
pancreatic infection, ductal perforation, stone formation,
and bleeding (if sphincterotomy is performed). In addition, PD stents may produce ductal damage, including
strictures or focal areas of chronic pancreatitis. These
changes may improve with time22,23 and are more likely
to be inconsequential in patients with advanced chronic
pancreatitis than those with a relatively normal pancreas.
Patients with CP have an increased risk of pancreatic
cancer. The endoscopist must maintain a high index of
suspicion of underlying cancer whenever treatment of
Obstructing pancreatic stones may contribute to abdominal pain or acute pancreatitis in patients with CP.
ERCP provides direct access to the PD for evaluation
and treatment of symptomatic PD stones. In one randomized trial of endoscopic and surgical therapy, surgery was
superior for long-term pain reduction in patients with
painful obstructive CP.25 However, because of its lower degree of invasiveness, endotherapy may be preferred, reserving surgery as second-line therapy for patients in
whom endoscopic therapy fails or is ineffective. PD stone
removal can be challenging. Frequently the stone configuration and size coupled with PD strictures occludes the lumen. Adjuvant endoscopic approaches such as stricture
dilation, intraductal lithotripsy, and pancreatic sphincterotomy may be needed. Even when accessible, PD stones
(which are often dense and hardened) may be impacted,
requiring extracorporeal shock wave lithotripsy (ESWL) to
fragment the stones before endoscopic removal can be
achieved. Patients frequently require several ESWL sessions to achieve stone clearance from the duct.26 Although
some investigators have reported high success rates with
this technique27 (with or without pancreatic stents),
others have had much less impressive results, with improvement in pain seen in as few as 35% of patients,
whereas other large series have reported that, despite successful ESWL, most patients experience no improvement
in pain.26,28 A recent large review of the ESWL literature
concluded that ESWL can result in complete duct clearance in as many as 50% of patients and in PD decompression.29 Intraductal lithotripsy guided by pancreatoscopy
has also been used to fragment PD stones.30
Case series have shown mixed results with regard to improvement in pain with pancreatic endotherapy. Some encouraging short-term and long-term follow-up to 5 years
showing improvements in pain (77%-100% and 54%-86%,
respectively) have been reported.31,32 One large series of
1000 patients with CP with long-term follow-up found
that 65% of patients with strictures, stones, or strictures
and stones had improvement in pain after endotherapy.
Twenty-four percent of patients ultimately required some
form of surgery to treat their CP.33 Others have found
similar outcomes, with clinical improvement rates of approximately 70%.29 Although modest, these success rates
934 GASTROINTESTINAL ENDOSCOPY Volume 63, No. 7 : 2006
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The role of endoscopy in patients with chronic pancreatitis
are acceptable in the context of a traditionally difficult-tomanage group of patients.
Although most studies suggest that endotherapy does
not improve pancreatic function, one recent MRCP-based
secretin study suggests that pancreatic exocrine function
can improve after endoscopic therapy.34
PANCREATIC DUCT LEAKS
PD disruptions or leaks can occur as a result of chronic
pancreatitis from a blowout upstream to obstructing strictures or stones. Pancreatic leaks can result in pancreatic
ascites, pleural effusions, pseudocyst formation, and internal and external pancreatic fistulas. PD leaks can often be
treated with endoscopic placement of transpapillary stents
in a manner similar to the use of biliary stents to close bile
duct leaks.35 Endoscopic therapy is successful in closing
the leak in approximately 60% of patients.36,37 Factors associated with a better outcome in duct disruption include
a partial disruption, successfully bridging the disruption
with a stent, and longer duration of stent placement (approximately 6 weeks). There are no comparative studies of
surgical, medical, and endoscopic therapy for treatment of
PD leaks.
PANCREATIC PSEUDOCYSTS
Pancreatic pseudocysts arise as a complication of
CP.38,39 Pancreatic pseudocysts complicate the course of
CP in 20% to 40% of cases. In general, the indications
for drainage of a pseudocyst are symptom driven. Pseudocyst size itself is not an indication for drainage. Pseudocyst
drainage should be considered for symptomatic lesions
(abdominal pain, gastric outlet obstruction, early satiety,
weight loss, or jaundice), infection, or progressive enlargement, even if asymptomatic. Special care must be taken to
avoid drainage of cystic neoplasms, duplication cysts, and
other noninflammatory fluid collections. EUS can be especially helpful with this determination.40 A guideline on the
endoscopic management of pseudocysts has been previously published.39
common bile duct strictures. Endoscopic therapy has
been used as an alternative to surgery.41 Plastic biliary
stents are a useful short-term treatment of these CPinduced common bile duct strictures in the setting of
cholestasis, jaundice, or cholangitis and may be used
as a long-term treatment approach in poor surgical
candidates. Unfortunately, long-term success rates are as
low as 10% in some studies.42,43 Patients with calcifications
of the pancreatic head have the poorest response to endoscopic therapy, with as few as 7.7% of patients achieving
clinical success at 1 year when single large-bore stents are
used.43
Balloon dilation of biliary strictures in the setting of CP
followed by insertion of multiple large-bore plastic stents
in an attempt to provide a more effective dilation is a relatively new approach. Unfortunately these strictures tend
to be recalcitrant and the restenosis rate after stent removal is high. Despite these drawbacks, the use of multiple stents with frequent stent exchanges and balloon
dilations over a long period of time (up to 1-2 years)
may be more efficacious than single stents for the treatment these strictures.44,45 Patient selection is critical in
this setting because patients need to return frequently
for stent changes. Poor compliance with follow-up can
lead to biliary sepsis from stent occlusion.45,46
Uncovered self-expanding metal stents (SEMS) have
been used to manage biliary strictures in patients with
CP who are poor operative candidates.47-49 At follow-up
approaching 3 years, good stent patency has been reported, and most subsequent stent occlusions can be
managed nonoperatively, although uncovered stents are
not removable. Some patients treated with this approach
may still ultimately require surgery. The placement of
short-length stents does not appear to preclude operative
intervention in the future. More recently, some authors
have used covered SEMS because of their potential removability, but results have been mixed.50,51 The routine use of
biliary SEMS for this indication is not recommended at this
time.
As in the management of PD strictures, the coexistence
of pancreatic cancer must be considered when endoscopic therapy of a biliary stricture is undertaken in the
setting of CP.
BILIARY OBSTRUCTION IN CHRONIC
PANCREATITIS
EUS-GUIDED CELIAC PLEXUS BLOCKADE
Distal common bile duct strictures have been reported
to occur in 2.7% to 45.6% of patients with CP. These
strictures can occur from inflammation, fibrosis, or compression from a pseudocyst or PD stone.2 Because longstanding biliary obstruction can lead to secondary biliary
cirrhosis or recurrent cholangitis, biliary decompression
is recommended in patients with clinically significant
obstruction (eg, cholestasis or jaundice). Surgical biliary
bypass is the standard approach for managing chronic
The celiac plexus sits astride the celiac artery and mediates pain impulses from, among other abdominal structures, the pancreas. Chronic inflammation in CP can
lead to debilitating pain, although pain in this setting
may be multifactorial in origin. Long-term pain management in these patients can be difficult. Patients with CP
are rarely considered for celiac plexus neurolysis (ablation) because of the risks of injecting absolute alcohol,
which have been addressed in another guideline.52
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Volume 63, No. 7 : 2006 GASTROINTESTINAL ENDOSCOPY 935
The role of endoscopy in patients with chronic pancreatitis
1. Steer ML, Waxman I, Freedman S. Chronic pancreatitis. N Engl J Med
1995;332:1482-90.
2. Delhaye M, Arvanitakis M, Bali M, et al. Endoscopic therapy for chronic
pancreatitis. Scand J Surg 2005;94:143-53.
3. Axon AT, Classen M, Cotton PB, et al. Pancreatography in chronic pancreatitis: international definitions. Gut 1984;25:1107-12.
4. Forsmark CE, Toskes PP. What does an abnormal pancreatogram
mean? Gastrointest Endosc Clin North Am 1995;5:105-23.
5. Schofl R. Diagnostic endoscopic retrograde cholangiopancreatography. Endoscopy 2001;33:147-57.
6. Sahai AV. EUS and chronic pancreatitis. Gastrointest Endosc 2002;
56(Suppl):S76-81.
7. Bruno MJ. Chronic pancreatitis. Gastrointest Endosc Clin North Am
2005;15:55-62, viii.
8. Sahai AV, Zimmerman M, Aabakken L, et al. Prospective assessment of
the ability of endoscopic ultrasound to diagnose, exclude, or establish
the severity of chronic pancreatitis found by endoscopic retrograde
cholangiopancreatography. Gastrointest Endosc 1998;48:18-25.
9. Wallace MB, Hawes RH, Durkalski V, et al. The reliability of EUS for the
diagnosis of chronic pancreatitis: interobserver agreement among experienced endosonographers. Gastrointest Endosc 2001;53:294-9.
10. Kahl S, Glasbrenner B, Leodolter A, et al. EUS in the diagnosis of early
chronic pancreatitis: a prospective follow-up study. Gastrointest Endosc 2002;55:507-11.
11. Hollerbach S, Klamann A, Topalidis T, et al. Endoscopic ultrasonography (EUS) and fine-needle aspiration (FNA) cytology for diagnosis of
chronic pancreatitis. Endoscopy 2001;33:824-31.
12. DeWitt J, McGreevy K, LeBlanc J, et al. EUS-guided Trucut biopsy of
suspected nonfocal chronic pancreatitis. Gastrointest Endosc 2005;
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13. Deshpande V, Mino-Kenudson M, Brugge WR, et al. Endoscopic ultrasound guided fine needle aspiration biopsy of autoimmune pancreatitis: diagnostic criteria and pitfalls. Am J Surg Pathol 2005;29:1464-71.
14. Levy MJ, Reddy RP, Wiersema MJ, et al. EUS-guided trucut biopsy in
establishing autoimmune pancreatitis as the cause of obstructive
jaundice. Gastrointest Endosc 2005;61:467-72.
15. Cremer M, Deviere J, Delhaye M, et al. Stenting in severe chronic pancreatitis: results of medium-term follow-up in 76 patients. Endoscopy
1991;23:171-6.
16. Binmoeller KF, Jue P, Seifert H, et al. Endoscopic pancreatic stent
drainage in chronic pancreatitis and a dominant stricture: long-term
results. Endoscopy 1995;27:638-44.
17. Smits ME, Badiga SM, Rauws EAJ, et al. Long-term results of pancreatic
stents in chronic pancreatitis. Gastrointest Endosc 1995;42:461-7.
18. Ponchon T, Bory R, Hedelius F, et al. Endoscopic stenting for pain relief
in chronic pancreatitis: results of a standardized protocol. Gastrointest
Endosc 1995;42:452-6.
19. Topazian M, Aslanian H, Andersen D. Outcome following endoscopic
stenting of pancreatic duct strictures in chronic pancreatitis. J Clin
Gastroenterol 2005;39:908-11.
20. Morgan DE, Smith JK, Hawkins K, et al. Endoscopic stent therapy in advanced chronic pancreatitis: relationships between ductal changes,
clinical response, and stent patency. Am J Gastroenterol 2003;98:
821-6.
21. Ammann RW, Akovbiantz A, Larglader F, et al. Course and outcome
of chronic pancreatitis: longitudinal study of a mixed medical-surgical
series of 245 patients. Gastroenterology 1984;86:820-8.
22. Sherman S, Hawes RH, Savides TJ, et al. Stent-induced pancreatic ductal and parenchymal changes: correlation of endoscopic ultrasound
with ERCP. Gastrointest Endosc 1996;44:276-82.
23. Smith MT, Sherman S, Ikenberry SO, et al. Alterations in pancreatic
ductal morphology following polyethylene pancreatic stent therapy.
Gastrointest Endosc 1996;44:268-75.
24. Faigel DO, Eisen GM, Baron TH, et al. Standards of Practice Committee.
American Society for Gastrointestinal Endoscopy: tissue sampling and
analysis. Gastrointest Endosc 2003;57:811-6.
25. Dite P, Ruzicka M, Zboril V, et al. A prospective, randomized trial comparing endoscopic and surgical therapy for chronic pancreatitis. Endoscopy 2003;35:553-8.
26. Brand B, Kahl M, Sidhu S, et al. Prospective evaluation of morphology,
function, and quality of life after extracorporeal shockwave lithotripsy
and endoscopic treatment of chronic calcific pancreatitis. Am J Gastroenterol 2000;95:3428-38.
27. Kozarek RA, Brandabur JJ, Ball TJ, et al. Clinical outcomes in patients
who undergo extracorporeal shock wave lithotripsy for chronic calcific
pancreatitis. Gastrointest Endosc 2002;56:496-500.
28. Adamek HE, Jakobs R, Buttmann A, et al. Long term follow up of patients with chronic pancreatitis and pancreatic stones treated with extracorporeal shock wave lithotripsy. Gut 1999;45:402-5.
29. Guda NM, Freeman ML, Smith C. Role of extracorporeal shock wave
lithotripsy in the treatment of pancreatic stones. Rev Gastroenterol
Disord 2005;5:73-81.
30. Howell DA, Dy RM, Hanson BL, et al. Endoscopic treatment of pancreatic duct stones using a 10F pancreatoscope and electrohydraulic
lithotripsy. Gastrointest Endosc 1999;50:829-33.
31. Lehman GA. Role of ERCP and other endoscopic modalities in chronic
pancreatitis. Gastrointest Endosc 2002;56(6 Suppl):S237-40.
936 GASTROINTESTINAL ENDOSCOPY Volume 63, No. 7 : 2006
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EUS-guided celiac plexus blockade can be performed in
patients with intractable pain from CP. This involves the injection of an anesthetic agent (ie, bupivacaine) in combination with a steroid agent (ie, triamcinolone) in an
effort to produce short- to medium-term cessation of
pain (typically less than 24 weeks).53 In the few direct
comparisons available, EUS-guided celiac plexus blockade
was less expensive and more effective and had a longer
duration of action that CT-guided celiac plexus blockade.
Because only 50% of patients can be expected to respond
to any form of celiac plexus blockade, many patients will
still require analgesic medication.54,55 Definitive data favoring EUS-guided blockade compared with other techniques or pain management approaches are not yet
available.
SUMMARY
d
d
d
d
d
d
ERCP and EUS are useful for the diagnosis of CP and associated pancreatic ductal complications (B).
ERCP for the diagnosis of CP should be reserved for patients in who the diagnosis has not been established by
noninvasive or less-invasive studies (C).
Endoscopic therapy of pancreatic ductal obstruction can
provide short-term relief of abdominal pain and longterm relief in some patients (B).
ERCP is effective for the short-term treatment of common bile duct obstruction resulting from CP (B) and
long-term treatment in poor operative candidates (C).
Endoscopically placed pancreatic duct stents are effective for the nonsurgical management of pancreatic strictures, duct leaks, and disruptions (B).
EUS-guided celiac blockade can effectively provide
short-term pain relief in patients with CP (B).
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Volume 63, No. 7 : 2006 GASTROINTESTINAL ENDOSCOPY 937
Disclosure: This article was not subject to the peer review process of GIE.
Prepared by:
STANDARDS OF PRACTICE COMMITTEE
Douglas G. Adler, MD
David Lichtenstein, MD
Todd H. Baron, MD, Chair
Raquel Davila, MD
James V. Egan, MD
Seng-Ian Gan, MD
Waqar A. Qureshi, MD
Elizabeth Rajan, MD
Bo Shen, MD
Marc J. Zuckerman, MD
Kenneth K. Lee, MD, NAPSGHAN Representative
Trina VanGuilder, RN, SGNA Representative
Robert D. Fanelli, MD, SAGES Representative