a 58-year-old woman with recurrent ruq pain julie fagan, m.d. primary care conference 7 july 2004
TRANSCRIPT
A 58-year-old woman with recurrent RUQ pain
Julie Fagan, M.D.
Primary Care Conference
7 July 2004
Learning Objectives
Recognize biliary sources of abdominal painList differential diagnosis of RUQ painDescribe diagnostic algorithm for evaluating RUQ painEvaluate evidence for treatment of various causes of RUQ pain
COI Disclaimer
No financial support was given for this presentation
Case Presentation
58 y/o WF with recurrent abdominal pain for many yrs11/97: recurrent epigastric/upper abdominal pain relieved by H2 blockers, omeprazole FHx: + for GERD, metastatic adenoCA of
unknown primary, likely GI SHx: married, 2 children, technology
instructor, no tobacco, EtOH, NSAIDs PMHx: obesity (fen/phen tx), no surgery
Case Presentation
Meds: omeprazole 20 mg/day, MVI
ROS: negative for wt loss; positive for occasional diarrhea, nausea, radiation to back (flank)
Exam: obese, no jaundice, mild epigastric tenderness, no masses or peritoneal signs, otherwise normal
Case Presentation
Labs: CBC, ESR, LFTs, amylase, lipase WNLGB u/s in past had showed GB polyps, no gallstonesPt was referred to GI, who diagnosed her with IBS, GERD and recommended a barium enema, which was normal
Case
1/6/99: attack of sharp RUQ pain radiating to back, shoulder, lasted 20 minutes. Took extra Gas-Ex, famotidine
5/99: EGD showed nonobstructing distal esophageal stricture, diaphragmatic hernia
Seen periodically in next 5 yrs with dyspepsia, GERD sx, RUQ pain
Case
6/04: complained of most severe episode ever of RUQ pain radiating to backRecent intentional 60-lb weight lossSelf- discontinued omeprazole, no more
GERD sx
Pain lasted several hours, triggered by eating cheese
Case
Exam: Weight 174, no sclericterus. 140/84, 84. Afebrile
Abdomen: no masses, tenderness, hepatosplenomegaly
Labs: again, all nl (CBC, chem 7, LFTs, amylase, lipase
Differential Diagnosis
Recurrent pancreatitis
Acalculous biliary pain (ABP)
Malignancy of gallbladder, pancreas, CBD
DyspepsiaGastritis or PUDNon-ulcer dyspepsia
Differential Diagnosis
IBS/functional abdominal painBut no alterations in bowel function
Dysfunction of the sphincter of Oddi
R sided pyelonephritis
Hepatic or subphrenic abscess
How to Proceed Next?
HIDA (hepatobiliary) scan 6/04: No ejection fraction response to
cholecystokinin after 30 minutes Consistent with biliary dyskinesis
Sphincter of Oddi Dysfunction (SOD)
Definition: a functional disturbance of the sphincter of Oddi (SO) leading to intermittent biliary obstruction
Other terms used: Papillary stenosis, sclerosing papillitis,
biliary spasm, stenosis of the SO, biliary dyskinesia, post-cholecystectomy syndrome
Function of the Sphincter of Oddi
To maintain a low-pressure system within the hepatic ductsAllows hepatic secretion to proceed
irrespective of bile flow rate
Symptoms of SOD
2 distinct syndromesBiliary pain without other causes
Frequently seen after cholecystectomySurgery may unmask SOD, since
gallbladder can decompress biliary system during sphincter spasm
Idiopathic recurrent pancreatitisMay explain many cases of post-ERCP
pancreatitis
Symptoms
Pancreatitis: unsure whether cause or effect22% of pts with known cause of
pancreatitis (e.g. alcohol, gallstones) had elevated SO pressures
SOD found in up to 87% of patients with chronic pancreatitis in another study
Diagnosis
Gold standard: SO manometry during ERCP
Less invasive tests:Dilation of CBD (5-10 mm)
Occurs in 16% of asymptomatic pts after cholecystectomy
Increases with ageProvocative testing
Diagnosis
Provocative tests to increase bile flow Fatty meal ultrasonography Cholecystokinin
In normal subjects, bile duct diameter should stay the same or decrease
An increase of > 2 mm considered abnl
Hepatobiliary scintigraphy
HIDA scans
HIDA is an iminodiacetic acid derivative, which is given by intravenous injection, taken up by hepatocytes, and excreted into bile with concentration in the gallbladder. Failure to opacify the gallbladder is the most sensitive and specific finding
Hepatobiliary Scintigraphy
HDTT (transit time from hepatic hilum to duodenum is measured in post-cholecystectomy patients
Gallbladder ejection fraction (amount of contrast that leaves the gallbladder after a CCK injection for patients with suspected acalculous biliary pain
Accuracy of HIDA
Varying results in post-cholecystectomy patients when compared with SO manometrySensitivity: 13%Specificity: 95%Positive predictive value: 50%Negative predictive value: 74%Craig et al, Gut 2003
Classification of SOD
Methods of predicting SOD and its response to treatment
Milwaukee classification (Hogan & Geenen) is most widely usedBased on clinical presentation, lab
results, ERCP findingsDivides patients with biliary pain into 3
groups
Milwaukee Classification of SOD (Biliary Type)
Criteria
A. Typical biliary-like pain
B. Elevated liver functions (AST and/or alkaline phosphatase (2-fold) on 2 or more occasions
C. Delayed drainage of contrast medium at ERCP (>45 minutes)
D. Dilated common bile duct with a corrected diameter >12mm at ERCP
Milwaukee Classification of SOD
Type I: all 4 criteria
Type II: biliary-type pain and 1 or 2 of the other criteria
Type III: biliary pain only, with no other objective abnormalities
Probability of SOD According to Classification
Type I: 65-95%
Type II: 50-63%
Type III: 12-28%
Pathophysiology
SO is a small sphincter that regulates the flow of bile and pancreatic enzymes into duodenum and prevents reflux of duodenal contents into ducts
SOD thought to cause pain by impeding flow of bile and pancreatic juice, with ductal hypertensiondistention and inflammation
Pathophysiology of SOD
Type 1 patients more likely to have structural abnormalities (papillary stenosis)
Conversely, Type III patients more likely to have dysmotility, high basal pressure, rapid contraction frequency, paradoxical response to CCK, excessive retrograde contractions High concordance of IBS
Clinical Presentation
Classic patient: female 20-50 with history of recurrent abdominal painRUQ or epigastricDisablingLasts 30 minutes-several hoursMay radiate to back or shoulderMay have N & VMay occur years after cholecystectomy
Clinical Presentation
Some pts have continual pain not relieved by surgery
Jaundice, fever, chills are rare
Physical Exam
Paucity of abnormal findings is the rule
Most common: mild, nonspecific abdominal tenderness
Pain usually not relieved by H2 blockers, PPI’s, antacids, IBS medications
Some pts present with typical pancreatic pain, recurrent pancreatitis
Diagnosis
LFTs (especially at time of biliary pain AST, alk phos, bili > 2 X upper limit of nl
Significant increase in amylase or lipase closely temporally related to pain episodes
Endoscopy to r/o UGI disease
Ultrasound to r/o gallstones, check CBD
Diagnosis
Ultrasound (cont)A CBD diameter > 6 mm may indicate
increased resistance through the SOBut found in 34% of asymptomatic
cholecystectomized patients
Fatty-meal or CCK-enhanced ultrasoundPatients without SOD should have
contraction of CBD, or no change
Diagnosis: Nardi Test
Morphine-prostigmine administered simultaneously induce SO spasm and pancreatic exocrine secretionRarely used: low sensitivity and specificityPoor correlation with outcome after sphincterotomyReplaced by other evaluations today
Diagnosis: Hepatobiliary Scintigraphy
Quantitation of bile flow through biliary tractFalse positives due to stones, tumors, sphincter diseasePrecise criteria for positive test controversial: time to peak, half-time of excretion, duodenal appearance time, hilum-to-duodenum transit time Most studies not correlated with manometry
MRCP
New tool with high sensitivity and specificity in distinguishing benign from malignant lesions (Lee et al Radiology 1997)Artifacts seen in presence of metal clips
Major limitation: unable to offer therapeutic options
Endoscopic Ultrasound
Most helpful for detecting microlithiasis (sludge) in ampullary region
Compared to MRI: 97% sensitivity and 88% specificity in diagnosing extrahepatic biliary obstruction
Fewer complications than ERCP, but invasive procedure often performed under general anesthesia by specialists
ERCP
Essential to r/o stones, tumors, or other obstructing processes of biliary tree
Definitive supine drainage times of biliary tree not well defined yet, but post-cholecystectomy biliary tree that fails to drain by 45 minutes generally considered abnormal
Sphincter of Oddi Manometry
Gold standard to diagnose SOD and stratify therapyHelpful selecting pts more likely to
benefit from sphincterotomy
Baseline sphincter pressure most helpful parameterMost important finding for SOD: basal pressure > 40 mm Hg
SO Manometry
Frequency of abnormal pressure 7-65% overallRange: 28-60% in Type II biliary pts7-55% among Type III biliary pts
Explanations for varianceSelection of pts with biliary-type vs
nonspecific abdominal pain increases yield of abnormal SOM
SO Manometry
Patients with SOD divided into 2 groupsStructural alterations of SO zone
(stenosis)Functional abnormalities (dyskinesia)
Sphincter of Oddi Stenosis
Basal SO pressure abnormally elevated (> 40 mm Hg)
Sphincter of Oddi Dyskinesia
Pts may also have elevated basal SO pressuresAdministration of amyl nitrate or
glucagon (to relax smooth muscles) dramatically decreases pressure
Smooth muscle relaxants do not reduce pressure in pts with SO stenosis
Other Features of SO Dyskinesia
Rapid SO contraction frequency (> 7/min)
Excessive retrograde phasic contractions (>50%)
Paradoxical basal pressure increase after CCK-8 administration
Limitations of SOM
Increased risk of pancreatitis (17% in some series) Compared to post-ERCP rate of 5%
Other studies suggest that SOD, not manometry, increases pancreatitis riskTechnique, equipment, sedation, observer experience affect results
Treatment
PharmacologicCalcium-channel blockers
NifedipineNitrates (case reports only)
ElectroacupunctureEndoscopic sphincterotomyBotoxSurgery
Nifedipine Effect on SOD
Conflicting resultsSublingual nifedipine (10-20 mg) had no
effect on SO pressure (Guelrud et al, Gastroenterology 95:1050)
Double-blind crossover trial showed improvement in biliary pain in 21/28 patients with SOD (Khuroo et al, Br. J Clin. Pharmacol. 33:477)
Electroacupuncture
One report from Korea (Lee et al Gastrointestinal Endoscopy 53:211)showed significant decreased SO pressure, amplitude and frequency of phasic contractions with stimulation of R lateral tibia Clinical relevance uncertain
Conclusions: Medical Therapy
Few studies use SOM as gold standard
Symptoms recur after therapy stopped
Most recommend medical therapy to screen Type I and II pts for sphincterotomy benefit
Most recommend a trial of medical therapy for type III patients Low-dose antidepressants, antispasmodics
Therapy: ES
Currently the recommended treatment for most patients
Surgery reserved for restenosis or when endoscopic therapy not available or feasible
Pain relief for Type I and II pts with ES is 90-95%
Botox
One study showed 50% reduction in SO pressure after injection of botulinum toxin May be helpful as trial to see if ES likely
to helpLimitations: expensive, invasive, short
duration of effect
Conclusions
SOD a relatively uncommon source of recurrent biliary-type pain or recurrent idiopathic pancreatitisDiagnosis can be elusiveMilwaukee classification helpful to predict type (stenosis vs dyskinesia) and response to therapySO manometry current gold diagnostic standard
Conclusions
Noninvasive techniques such as quantitative scintigraphy and MRCP may reduce need for ERCP, manometry
Pharmacologic treatment reserved for Type III patients Can be useful to screen Types I and II patients
for response to therapy
Endoscopic sphincterotomy still the definitive treatment
Patient Follow-Up
After reading about nifedipine on the Internet, the patient elected to see Gastroenterology for further w/u and possible treatment
The End