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