Approach to sphincter of Oddi dysfunction

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Approach to sphincter of Oddi dysfunction
Gregory A. Cote, MD, MS
Approach to sphincter of Oddi
dysfunction
Gregory A. Cote, MD, MS
A
Associate
i t P
Professor
f
off M
Medicine
di i
Medical University of South Carolina
Potential Sphincter of Oddi disorders
Recurrent
acute
pancreatitis
Biliary
• GB
dyskinesia
• Biliary SOD
Pancreatic
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Gregory A. Cote, MD, MS
Sphincter of Oddi
• Facilitates filling of the
ggallbladder for the
concentration and storage
of bile
• Relaxation in response to
food intake
• Neurohormonal control of
biliary
b
a y motility
ot ty involves
o es
sympathetic,
parasympathetic, and
enteric nerves
Rome III criteria for SO disorder
• Epigastric and/or RUQ
pain that meet all of the
following:
– Duration > 30 minutes
– Recurrence at differing
intervals
– Builds to a steadyy level
– Interrupts daily activities
http://www.romecriteria.org/criteria
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• NOT relieved by:
– BMs
BM
– Postural change
– Antacids
• Exclude other structural
disease that would
explain symptoms
Gregory A. Cote, MD, MS
Supportive criteria
• Associated nausea and
vomitingg
• Radiation to the back or
right infrascapular region
• Pain causes nocturnal
awakening
• Elevated serum liver
chemistries
Biliary
• Transient elevation in
serum liver chemistries
with episodes
• Duct dilation > 9mm
Pancreatic
• Transient elevation in
pancreas chemistries
h i t i >2
2x
ULN
• Duct dilation
– head >6mm, body >5mm
Modified Milwaukee classification
Type
yp
I
II
III
Rome III
symptoms
+++
+++
+++
Duct
Abnl
Dilation Laboratories
+++
+++
+++ OR
+++
-
Confirmation with sphincter of Oddi manometry, basal sphincter
pressure > 40mmHg
ACG Regional Postgraduate Course - Williamsburg, VA
Copyright 2014 American College of Gastroenterology
Gregory A. Cote, MD, MS
Criticisms
• High prevalence of concomitant:
– Small bowel dysmotility
– Visceral hyperalgesia
• Limited prospective data confirming a
response to endoscopic or surgical sphincter
ablation
Evans P, Bak Y-T, Dowsett J, et al. Dig Dis Sci 1997;42:1507-12.
Chun A, Desautels S, Slivka A, et al. Dig Dis Sci 1999;44:631-6.
Tests of sphincter function
Less invasive testing**
• Scintigraphy (biliary)
– CCK
– Fatty meal
• US, EUS, MRCP
– Duct compliance/Δ diameter
– Secretin
Manometry
• Aspiration catheter: low
compliance, water perfused
system
• Solid state catheter
• Highest risk indication for
ERCP
– Irrespective of manometry
technique
** Poor correlation with SOM and no correlation with
response to sphincterotomy
ACG Regional Postgraduate Course - Williamsburg, VA
Copyright 2014 American College of Gastroenterology
Gregory A. Cote, MD, MS
Definitions of “dysfunction”
Measure
Abnormal threshold
Basal sphincter pressure
> 40mmHg
Intraductal pressure
N/A
Phasic contractions
• Peak amplitude
• Duration (seconds)
• Frequency
(contractions/min)
> 350mmHg
N/A
>7
Behar et al., GIE 2006
Evidence for ERCP with SOM in 2013
SOD
Type
RCT
N
Improvement,
sham
Improvement, ES
P value
0.01
<0.005
I
None
II
Geenen,
NEJM 1989
47
30% (all)
25% (SOD)
~ 80-90%,
irrespective of SOM
65%
91% (SOD)
I-III
Toouli, Gut
2000
63
38% (SOD)
84% (SOD)
0.041
III
Sherman,
GIE 1994
(abstract)
29
30%
62%
n/a
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Copyright 2014 American College of Gastroenterology
Gregory A. Cote, MD, MS
Historical algorithm
Labs, US, EGD, EUS, MRCP
No structural
disease
Structural disease
Rx
Type I
Type II
Type III
ES
ERCP with
SOM
Pharmacological
trial
ERCP with SOM
Behar et al., GIE 2006
Medical therapy for SOD
Medical targets
Reduce spasm
Short acting calcium channel
blockers
Nitrates
Neuromodulators
TCA
SSRI
anticholinergics
Khuroo M, Zargar S, Yattoo G. Br J Clin Pharmacol 1992;33:477-85.
Craig A, Toouli J. Intern Med J 2002;32:119-20.
Cuer J, Abergel A, Dapoigny M, et al. Gastroenterology 1995;108:A412.
Vitton V, Ezzedine S, Gonzalez JM, Gasmi M, Grimaud JC, Barthet M. World J Gastroenterol 2012;18:1610-5.
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Gregory A. Cote, MD, MS
EPISOD
Suspected SOD III
(n=1,584)
Excluded (n=1,298)
Randomized (n=214)
Sham (n=73)
pSOD (n
(n=48)
48)
Nl SOM
(n=25)
Cotton P, et al. JAMA 2014
ES (n =141)
pSOD (n
(n=99)
99)
DES (n=47)
Nl SOM
(
(n=42)
)
BES (n=42)
BES (n=52)
From: Effect of Endoscopic Sphincterotomy for Suspected Sphincter of Oddi Dysfunction on Pain-Related
Disability Following Cholecystectomy: The EPISOD Randomized Clinical Trial
JAMA. 2014;311(20):2101-2109. doi:10.1001/jama.2014.5220
Figure Legend:
RAPID Score Distribution by Assigned Treatment Group and VisitThe boxes indicate interquartile ranges; circle within box, mean;
horizontal line within box, median; error bars, 1.5 times the interquartile range; and circles, outliers. RAPID indicates Recurrent
Abdominal Pain Intensity and Disability.
Date of download: 7/27/2014
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Copyright 2014 American College of Gastroenterology
Copyright © 2014 American Medical
Association. All rights reserved.
Gregory A. Cote, MD, MS
EPISOD outcome
Definition of success
• RAPID < 6 @ months 9 and
12
– < 6 days of lost productivity
• No need for repeat
intervention
• no need for narcotics
Outcome
100
80
60
40
20
0
Sham
ES
Historical Updated algorithm
Labs, US, EGD, EUS, MRCP
No structural
disease
Structural disease
Rx
Type I
Type II
Type III
ES
ERCP with
SOM
Pharmacological
trial
ERCP with SOM
ACG Regional Postgraduate Course - Williamsburg, VA
Copyright 2014 American College of Gastroenterology
Gregory A. Cote, MD, MS
IDIOPATHIC RECURRENT ACUTE
PANCREATITIS
Pancreatic duct obstruction is a cause
of acute pancreatitis
• How would SOD cause
RAP?
– Intermittent or sustained
intraductal pressure
• Duct obstruction/spasm
causes AP in animals
• Gallstone pancreatitis
exists
• ERCP
Mechanism of GS pancreatitis?
• Bile acid reflux into PD
• PD obstruction
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– Causes pancreatitis
– PD stenting decreases risk
– Over-injection increases
risk
Lerch M, et al. Gastroenterology 1993
Gregory A. Cote, MD, MS
2. SOD is prevalent (n=1854)
100%
80%
60%
40%
20%
0%
SOD
Not SOD
Adapted from Tan D and Sherman S., “Unexplained Acute Pancreatitis,” in Baron, Kozarek and Carr-Locke, ERCP 2nd
edition
RAP and SOD: Cause, Effect, Neither?
• Among individuals with CBD stones, those
having concomitant RAP have significantly
higher basal sphincter pressures
– This insinuates that pancreatitis (not
choledocholithiasis) is the link to SOD
• SOD is prevalent in chronic pancreatitis
S i l sphincteroplasty
Surgical
hi t
l t series
i (n=466,
( 466 22% for
f RAP)
Biopsy Site
# of bx/pts
Inflammation n (%)
Fibrosis n (%)
Ampulla
255/272
74 (29)
26 (10)
Transampullary septum
234/272
35 (15)
64 (27)
Guelrud M, et al. J Clin Gastroenterol 1983
Madura JA, et al. Arch Surg 2005
Okazaki K, Yamamoto Y, Ito K. Gastroenterology 1986
ACG Regional Postgraduate Course - Williamsburg, VA
Copyright 2014 American College of Gastroenterology
Gregory A. Cote, MD, MS
How often does acute pancreatitis
become RAP and iRAP?
Risk of recurrence
Age association
36% of 7,456 cases idiopathic
Yadav D, et al., Am J Gastro 2012
Relative Pro
obability of Recurren
nt AP
Considerations in RAP
Idiopathic
Metabolic (hypertriglyceridemia,
hypercalcemia), Medications
Genetics (CFTR, PRSS, SPINK1, CTRC)
Autoimmune
Obstructive (Divisum*, IPMN, tumors,
anomalous pancreatobiliary union))
Alcohol, Gallstones, Smoking
Cote GA. “ERCP in Acute and Recurrent Acute Pancreatitis,” In Cotton and Leung, ERCP, 2nd edition, in press
ACG Regional Postgraduate Course - Williamsburg, VA
Copyright 2014 American College of Gastroenterology
Gregory A. Cote, MD, MS
Be careful who you’re calling idiopathic
• Ampullary
lesions
• Divisum
• Small tumors
• Divisum
• Tumors
• IPMN
MRCP
EUS
S-MRCP
Genetics
• Divisum
• Early CP
• Younger age
• Family
history
• Divisum
Second tier diagnostics will identify an underlying etiology or factor in 40-75%
Wilcox CM, Varadarajulu S, Eloubeidi M. GIE 2006
Kaw M, Brodmerkel GJ, Jr. GIE 2002
What is the goal of sphincterotomy in
RAP?
• Eliminate future episodes of
AP
• Reduce the frequency of AP
episodes
• Reduce/eliminate
abdominal pain related to
RAP
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Gregory A. Cote, MD, MS
Pancreatic sphincter therapy for iRAP?
• 34 patients with normal pre-procedure evaluation and
then normal ERCP with SOM
– Randomization
• Serial PD stenting q3 months for 9 months (19)
• Sham (15)
• PD stenting
– 5 or 7Fr barbed stent
• All patients underwent repeat ERP every 3 months for
a total of 9 months of stenting
• Mean follow-up, including treatment
– Stent group = 33 months (range 13 - 77 months)
– Control group = 35 months (range 10 - 78 months)
Jacob L, et al. Endoscopy 2001
Results: less AP, unchanged pain
RAP
• Stent 2/19 (11%) vs. sham 8/15 (53%, p<0.02)
Pancreatic-type abdominal pain
• Stent 6/19 (32%) vs. sham 6/15 (40%, p<0.61)
Chronic pancreatitis
• Stent 5/19 (26%) vs. sham 4/15 (27%)
Jacob L, et al. Endoscopy 2001
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Copyright 2014 American College of Gastroenterology
Gregory A. Cote, MD, MS
Clinical trial of sphincter of Oddi
manometry in iRAP
ERCP with pancreatic SOM
Elevated (≥40mmHg) basal
pancreatic sphincter pressure
Biliary ES
Normal basal biliary and
pancreatic sphincter pressure
Sham
1:1
randomization
Dual ES
Biliary ES
Cote GA, et al. Gastroenterology 2012
Enrollment: 9/1997- 8/2011
Pre-ERCP work-up of those randomized:
CCY (65%) MRI/MRCP (35%) EUS (18%) Genetic Testing (42%)
Screen failure
(n=50)
· Pancreas divisum
(n=17)
· Chronic pancreatitis
(n=12)
· Other (CBD stone,
IPMN) (n=21)
Pancreatic SOD
(n=69)
BES (n=33)
DES (n=36)
RAP (n=139)
Normal SOM
(n=20)
Preliminary data
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Sham (n=9)
BES (n=11)
Gregory A. Cote, MD, MS
11% (sham)
27% (BES)
47% (DES)
49% (BES)
N=20,
p = 0.59
N=69,
p = 1.0
11% (sham)
27% (BES)
47% (DES)
49% (BES)
Chronic pancreatitis developed in 17% during f/u
(median 78 mos)
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N=20,
p = 0.59
N=69,
p = 1.0
Gregory A. Cote, MD, MS
11% (sham)
27% (BES)
47% (DES)
49% (BES)
N=20,
p = 0.59
N=69,
p = 1.0
11% (sham)
27% (BES)
SOD: Adjusted HR 4.2 (1.4-14.0)
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47% (DES)
49% (BES)
N=20,
p = 0.59
N=69,
p = 1.0
Gregory A. Cote, MD, MS
ERCP for RAP in 2014
• Work-up should be preceded by thorough
di
diagnostics
ti
– History, S-MRCP, EUS, genetics (?)
• CCY when gallstones likely
– Elevation in liver chemistries w/AP, gallstones
• Empiric biliary sphincterotomy unproven
• Pancreatic sphincterotomy unproven
Concluding remarks
• ERCP for suspected SOD only acceptable at
referral
f
l centers
t
– Medicolegal considerations
• Human studies on mechanisms of abdominal
pain and minimally invasive interventions
needed
• ERCP for abdominal pain only and IRAP should
not be performed in routine practice
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