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Frequency of abnormal pancreatic and biliary sphincter manometry compared with clinical suspicion of sphincter of Oddi dysfunction
Frequency of abnormal pancreatic and biliary sphincter manometry compared with clinical suspicion of sphincter of Oddi dysfunction Damian Eversman, MD, Evan L. Fogel, MD, Michael Rusche, MD, Stuart Sherman, MD, Glen A. Lehman, MD Indianapolis, Indiana Background: Sphincter of Oddi manometry as performed at ERCP is the most accepted method to evaluate for sphincter of Oddi dysfunction. To fully assess for sphincter of Oddi dysfunction, both the pancreatic and the bile ducts must be evaluated. We assessed the frequency of pancreatic and biliary sphincter abnormalities in a large series of patients. Methods: A total of 593 patients underwent manometry of the biliary and pancreatic ducts at one endoscopic retrograde cholangiopancreatography session. Basal sphincter pressure greater than or equal to 40 mm Hg was considered abnormal. Phasic waves were not evaluated. Manometric abnormalities were correlated with the clinical presentation as categorized using a modified Geenen/Hogan classification. Results: Of 360 patients with intact sphincters, 18.9% had abnormal pancreatic sphincter basal pressure alone, 11.4% had abnormal biliary basal sphincter pressure alone, and in 31.4% the basal pressure was abnormal for both sphincters; thus, 60.1% of the patients had sphincter dysfunction. The frequency of sphincter of Oddi dysfunction did not differ whether typed by biliary or pancreatic criteria: approximately 65% type II and 59% type III. Of patients without pancreatitis, 55.9% had an abnormal basal sphincter pressure, whereas sphincter dysfunction was present in 72.3% of those with idiopathic pancreatitis and 53.9% of patients with chronic pancreatitis. Of patients with an ablated biliary sphincter, 45.9% had abnormal basal pancreatic sphincter pressure and only 0.6% had an abnormal biliary sphincter pressure alone. Abnormal pressure in both sphincters was found in 9.3%. Conclusion: If both portions of the sphincter of Oddi are studied simultaneously, abnormalities are found very commonly (55% to 72%). Assessment of both sides of the sphincter is necessary. Classifying patients according to both pancreatic and biliary sphincter segments is cumbersome, and may be replaced by an overall type. Using this modified classification, the frequency of sphincter of Oddi dysfunction is similar in both type II and type III patients (59% to 67%). (Gastrointest Endosc 1999;50:637-41.)
Sphincter of Oddi m a n o m e t r y (SOM) may be useful when evaluating patients with idiopathic recurre n t pancreatitis, chronic pancreatitis or unexplained pancreatobiliary-type pain. It is considered by some to be the standard in assessing patients for sphincter of Oddi dysfunction (SOD) and to be helpful in selecting patients who are more likely to respond to sphinct e r ablation. 1-3 The f r equency of a b n o r m a l SOM varies in published series from 7% to 55%. 4-8 Most such studies report m a n o m e t r y dat a for either the pancreatic duct or the bile duct but not both. Some fail to report which duct was studied. To thoroughly assess the sphincter of Oddi, both the pancreatic and
Received March 5, 1999. Accepted July 2, 1999. From the Division of Gastroenterology/Ilepatology, Indiana University Medical Center, Indianapolis, Indiana. Reprint requests: Glen A. Lehman, MD, Division of Gastroenterology/Hepatology, Indiana University Medical Center, 550 N. University Blvd., Suite 2300, Indianapolis, IN 46202. Copyright 9 1999 by the American Society for Gastrointestinal Endoscopy 0016-5107/99/$8.00 + 0 37/1/101233 VOLUME 50, NO. 5, 1999
biliary segments m u s t be evaluated. This stu d y reports the m a n o m e t r y findings in a large series of patients in whom both pancreatic and biliary sphincter pressures were recorded at the same session. PATIENTS AND METHODS
Between 1993 and 1996, 682 patients at our institution underwent ERCP and attempted manometry of both biliary and pancreatic ducts for suspected SOD. Manometry of both ducts was successful in 593 patients who constitute the study population. Patients were excluded if pancreas divisum, bile duct stones, or pancreatobiliary malignancy was found at ERCP. Liver transplant patients were excluded. Patients with chronic pancreatitis by clinical evaluation or ductography were specifically included no matter what the etiology of the disease. The indication for SOM was to evaluate sphincter function in patients with (1) acute recurrent pancreatitis of unknown etiology, (2) acute or recurrent pancreatitis of documented or suspected etiology, (3) chronic pancreatitis of known or unknown etiology, or (4) pancreaticobiliary-type pain, with or without elevated liver or pancreatic enzymes or ductal dilatation on US/CT. GASTROINTESTINAL ENDOSCOPY 637
D Eversman, E Fogel, M Rusche, et al.
Abnormal sphincter manometry and sphincter of Oddi dysfunction
Table 1. Modified Milwaukee classification for possible sphincter of Oddi dysfunction: biliary type Biliary type I Biliary type II Biliary type III
Patients with biliary-type pain, ALT/AST/ALP1.1x normal documented on any occasion, and bile duct >10 mm diameter Patients with biliary-type pain but only one of the above criteria Patients with only biliary-type pain and no other abnormalities
ALT, Alanine aminotransferase; AST, aspartate aminotransferase; ALP, alkaline phosphatase. Ductal drainage times were not evaluated or used in this classification.
Table 2. Modified Milwaukee classification for possible sphincter of Oddi dysfunction: pancreatic type Pancreatic type I
Patients with pancreatic-type pain, amylase or lipase l a x normal documented on any occasion, pancreatic duct >6 mm in the head or >5 mm in body Pancreatic type II Patients with pancreatic-type pain but only one of the above criteria Pancreatic type III Patients with only pancreatic-type pain and no other abnormalities Ductal drainage times were not evaluated or used in this classification Based on clinical, radiographic, and laboratory data, patients were categorized according to a modified classification of SOD (biliary types I, II, III and pancreatic types I, II, III) (Tables 1 and 2). Each patient was classified twice; e.g., type I biliary (with a dilated bile duct) and type III pancreatic with normal caliber pancreatic duct and absence of pancreatic enzyme abnormality. The classification of patients included ERCP data but the determination was made before manometry. Because of this, chronic pancreatitis found only at ERCP would convert a classification of pancreatic type III to pancreatic type II. Fiftyone patients either continued to have symptoms or symptoms recurred after therapy and were studied again. In these cases, the original classification for each patient was maintained throughout the study.
Manometry technique SOM was performed at ERCP in the conventional retrograde fashion using a low-compliance infusion pump with a triple lumen 5F aspirating type catheter (previously described5). One of the three lumens was used to aspirate fluid from the duct to prevent over distention. Duct position was confirmed by aspiration of clear juice from the pancreatic duct or yellow fluid from the bile duct. Contrast media was also injected for diagnostic ductography and to confirm catheter location. The basal sphincter pressure was recorded as the baseline pressure between phasic waves using the duodenal luminal pressure as a zero reference. Recording was sustained a m i n i m u m of 30 seconds, and generally more t h a n 1 minute; pressures were recorded in at least two leads. The four-point method was used to determine the most representative segment for measurement of the basal pressure. 9 The four lowest points in the highest sustained sphincter pressure zone are read and averaged in this method. The mean of all basal sphincter recordings (combining all leads and all pull throughs) was taken as the actual basal sphincter pressure for data analysis. Biliary and pancreatic sphincter data were tallied separately. A basal sphincter pressure greater than or equal to 40 mm Hg was considered abnormal.10 Only basal 638 GASTROINTESTINAL ENDOSCOPY
sphincter pressure was evaluated; phasic wave amplitude and duration were disregarded. Tracings were interpreted on the day they were recorded, strictly as normal or abnormal for each patient. Pancreatic and biliary duct diameters were determined radiographically as follows: the widest diameter of the common bile duct and common hepatic duct were measured and if either was greater than 10 mm in diameter (after correction for magnification) the duct was considered dilated. This classification was used regardless of whether the gallbladder had previously been removed. The pancreatic duct was considered abnormal if the corrected diameter of the main duct in the head was greater than 6 mm or greater t h a n 5 mm when measured in the body. Sedation for m a n o m e t r y was achieved with diazepam alone in 256 patients, and diazepam plus meperidine in 337 patients.ll, 12 When used, meperidine dose was limited to 1 mg/kg or less until SOM was completed. Anticholinergics and other drugs known to affect the sphincter were not administered during ERCP or within 12 hours before the examination.
RESULTS Of the 593 patients who participated in the study, 125 had acute recurrent pancreatitis of unknown etiology, 30 had acute recurrent pancreatitis with a suspected etiology, 26 had chronic pancreatitis, and 412 had pancreatobiliary-type pain. Liver s e r u m chemistries and pancreatic s e r u m e n z y m e s w e r e a s s e s s e d in all p a t i e n t s . C h o l e c y s t e c t o m y h a d b e e n p e r f o r m e d in 402 (67.6%) p a t i e n t s , 231 (39.1%) h a d p r i o r a b l a t i o n of t h e biliary sphincter, a n d 61 (10.2%) h a d p r i o r ablation of the p a n c r e a t i c sphincter.
Patients with intact sphincters Table 3 s h o w s t h e f r e q u e n c y of b a s a l s p h i n c t e r p r e s s u r e a b n o r m a l i t i e s in biliary t y p e s I, II, I I I a n d Table 4 s h o w s s i m i l a r d a t a for p a n c r e a t i c t y p e s I, II, VOLUME 50, NO. 5, 1999
Abnormal sphincter manometry and sphincter of Oddi dysfunction
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Table 3. Frequency of abnormal basal sphincter pressure in patients with intact sphincters Biliary type I
Patient No.
III II I Total
214 123 23 360
Pancreas alone 37 27 4 68
Biliary alone
(17.3%) (22.0%) (17.4%) (18.9%)
23 14 4 41
(10.7%) (11.4%) (17.4%) (11.4%)
Both 67 39 7 113
(31.3%) (31.7%) (30.4%) (31.4%)
Total 127 80 12 219
(59.3%)* (65.0%)* (65.2%)* (60.1%)
*p = Not significant.
Table 4. Frequency of abnormal basal sphincter pressure in patients with intact sphincters Pancreatic type
Patient No.
III II I Total
253 106 1 360
Pancreas alone 45 (17.8%) 23 (21.7%) 0 68 (18.9%)
Biliary alone
Both
33 (13.0%) 8 (7.6%) 0 41 (11.4%)
72 (28.5%) 40 (37.8%) 1 (100.0%) 113 (31.4%)
Total 150 (59.3%)* 71 (67.0%)* 1 (100.0%)* 222 (61.7%)
*p = Not significant.
Table 5. Frequency of abnormal basal sphincter pressure in patients with type II intact sphincters (typed using overall criteria) Patient No. All patients No pancreatitis Idiopathic pancreatitis Chronic pancreatitis
194 136 47 39
Pancreas alone 43 31 12 7
Biliary alone
(22.2%) (15.4%) (25.5%) (17.9%)
18 18 3 3
(9.3%) (13.2%)
(6.4%) (7.7%)
Both 66 37 19 11
(34.0%) (27.2%) (40.4%) (28.2%)
Total 127 76 34 21
(65.5%)a (55.9%)b (72.3%)c (53.9%)d
p < 0.05: a vs. b; b vs. c; c vs. d. p = Not significant: a vs. c; a vs. d; b vs. d.
III. Because the numbers of type I patients in the pancreatic and biliary groups were relatively small, these patients were not sub-categorized. The frequency of abnormalities was nearly identical regardless of which classification (biliary or pancreatic) system was used. Therefore, the data were combined and patients were categorized according to worst parameter (e.g., if the patient was biliary type II and pancreatic type III, then overall type II was the final classification). Classification yielded 194 overall type II patients with intact sphincters and 143 overall type III patients with intact sphincters. To further characterize this group, the presence of idiopathic and chronic pancreatitis was evaluated separately. In the overall type III category, there were 143 patients. This included five patients who had no clinical history of pancreatitis and normal serum enzymes. At their first ERCP, pancreatographic changes consistent with chronic pancreatitis were found. Four of the five (80%) had abnormal basal sphincter manometry; three had both biliary and pancreatic duct abnormalities, and one had isolated elevated biliary basal sphincter pressure. In the other patient manometry of both ducts was normal. Table 5 shows the frequency of abnormal basal sphincter pressures (with intact sphincters) in patients with or without idiopathic and chronic pan~ creatitis classified as overall type II. If a patient had VOLUME 50, NO. 5, 1999
a clinical history suggestive of idiopathic pancreatitis but was found to have chronic pancreatitis by pancreatography, then both categories were used for classification purposes.
Patients with previous sphincter ablation In patients who remained symptomatic or did not have long-term pain relief with sphincter therapy, prior biliary sphincter ablation usually produced normal biliary basal sphincter pressures; however, pancreatic sphincter pressure remained abnormal in more than half of the patients (Table 6). After both sphincters were ablated, 20% of patients still had abnormal pancreatic or biliary sphincter pressure.
Patients with prior cholecystectomy Cholecystectomy had been performed in 402 of 593 patients (67.6%) before ERCP and SOM. In this group, 55.7% of patients had SOD: 24.8% had elevated pancreatic sphincter pressure alone, 8.5% had elevation of the biliary sphincter pressure alone, and 22.4% had elevated pancreatic and biliary sphincter pressures. In the 191 patients with gallbladders, the frequency of SOD was virtually identical at 55%: 28.3% had elevated pancreatic sphincter pressure alone, 4.2% had elevated biliary sphincter pressure alone, and 22.5% had elevated pancreatic and biliary sphincter pressures. GASTROINTESTINAL ENDOSCOPY (}39
D Eversman, E Fogel, M Rusche, et al.
Abnormal sphincter manometry and sphincter of Oddi dysfunction
Table 6. Frequency of abnormal basal sphincter pressure after sphincter ablation Biliary ablated Both ablated Total
Patient No.
Pancreas alone
172 60 232
79 (45.9%) 8 (13.3%) 87 (37.5%)
DISCUSSION Sphincter of Oddi dysfunction is a recognized cause of pancreatitis, cholestasis, and pancreatobiliary-type pain. SOM is now the most commonly used method to evaluate the sphincter for SOD. The frequency of abnormal basal sphincter pressure has varied greatly in reported series which may be a reflection of the patient population assessed, which ductal system was assessed and the criteria used to define the limits of normal. Measurements of both pancreatic and biliary components of the sphincter are necessary to thoroughly evaluate the sphincter mechanism.13-15 Discordance is present if the manometry findings with respect to the biliary duct (normal or abnormal) differ from those for the pancreatic duct. Our data confirm that in previously untreated patients discordance is high. Rolney et al. 13 found that 53% of 17 patients had manometry results that differed (normal versus abnormal) with regard to the distinct sphincter segments. In this present series of 360 previously untreated patients the discordance rate varied from 26% to 35% depending on the patient category assessed. Therefore, the assumption that manometric findings with respect to one duct would be the same for the other would be correct in only 65% to 74% of the cases. Classification systems have been used to identify patients who might require manometry to determine the need for sphincter ablation. These have used clinical data, laboratory tests, radiographic measurements, and ductal drainage time. Routinely, only the bile duct sphincter component has been evaluated. However, our study data show that both ducts should be evaluated. Therefore, it becomes necessary to classify each patient with respect to both the biliary and pancreatic components of the sphincter. This cumbersome method can be abandoned in favor of one overall type; when two types are distinguished there appears to be little difference between them in predicting abnormal basal pressure. A single overall classification would lead to more uniform groupings of patients, thereby making data more applicable in clinical practice. Furthermore, when both sides of the sphincter are evaluated, there is little difference in the frequency of SOD according to the modified Geenen-Hogan classification used in this study. 640
GASTROINTESTINAL ENDOSCOPY
Biliary alone 1 (0.6%) 0 1 (0.43%)
Both
Total
16 (9.3%) 4 (6.7%) 20 (8.6%)
96 (55.8%) 12 (20.0%) 108 (46.6%)
The frequency at which sphincter abnormalities are detected is a major factor in determining the utility of SOM. The frequency of abnormal biliary manometry has been reported to vary from 28% to 60% for biliary type II patients. The frequency in biliary type III patients has varied more markedly from 7% to 55%. This wide variance has not been helpful in deciding whether to use manometry in patients who have pain as the only manifestation of possible SOD. Risk-to-benefit ratio is another major determinant of the utility of SOM. The study of Freeman et alJ 7 found similar complication rates for endoscopic sphincterotomy in patients with documented versus suspected SOD. The complication rate was 21% for patients who underwent manometry and 25% for those who did not have preceding manometry. This suggests that the high complication rates are intrinsic to the study group and the therapy applied rather than the manometry itself. 17 Routine use of pancreatic stents during sphincterotomy has been shown to decrease the pancreatitis rates in preliminary studiesJS, 19 In this study the frequency of SOD was high in patients with idiopathic pancreatitis (72.3%) and chronic pancreatitis (53.9%). Elevated basal sphincter pressure has long been accepted as a potential etiology in patients with idiopathic pancreatitis. The increased incidence of SOD in this group, compared with that of earlier studies, reflects the importance of evaluating both the pancreatic and biliary sphincter components. With regard to the association between SOD and chronic pancreatitis, it is unclear whether generalized scarring also involves the sphincter mechanism, leading to SOD, or the hypertensive sphincter causes elevated pressure upstream leading to morphologic changes. At present, this association between chronic pancreatitis and SOD appears to warrant further research. It is not suggested that SOM be considered part of the routine evaluation of patients with chronic pancreatitis. There are several plausible explanations for the marked differences in frequencies of basal sphincter pressure abnormalities in the various published s e r i e s . 7,14,15 First, selection of patients with a pain pattern that is typical of biliary tract disease versus a nonspecific pattern as might be seen with the irritable bowel syndrome will probably increase the VOLUME 50, NO. 5, 1999
Abnormal sphincter manometry and sphincter of Oddi dysfunction
percentage of patients with SOD. Second, if abnormal sphincter pressure is required in two or three recording channels to make the diagnosis of SOD, as opposed to the mean of all channels, then the frequency of SOD will be lower. The use of different equipment in these studies (e.g., Arndorfer catheter versus a triple-lumen aspiration catheter) may also be a factor, but this is difficult to quantify. Third, assessment of only one sphincter component versus both will lower the observed frequency of SOD. With assessment of only one component, the frequency of SOD may be higher in type II patients (i.e., abnormal SOM in patients with elevated liver function tests) than type III patients, a difference which may not be evident with performance of dual sphincter manometry. After biliary ablative therapy the vast majority of patients had normal biliary sphincter pressure, even if still symptomatic (the reason for repeating the study). However, a high percentage of these symptomatic patients will have abnormal residual pancreatic sphincter pressure. This raises the question whether patients with both pancreatic and biliary sphincter pressure abnormalities should be treated with biliary sphincterotomy alone. We are conducting retrospective and prospective studies to determine the frequency of pain relief with biliary versus combined pancreatobiliary sphincterotomy in these groups of patients. This large series confirms that abnormalities occur in both pancreatic and biliary segments of the sphincter of Oddi in highly symptomatic patients. Measuring sphincter pressure in both segments is necessary to determine the full extent of SOD. Patients with idiopathic pancreatitis and those with chronic pancreatitis appear to have abnormal sphincter pressures as often as those without pancreatitis. A single classification of patients based on the worst parameter appears to have the same utility as a double classification based on measurements from each segment of the sphincter. Further studies are needed to determine the optimal thera9 py for patients in whom both sphincters are abnormal as well as those with isolated pancreatic sphincter abnormalities. REFERENCES 1. Kalloo AN, Pasricha PJ. Therapy of sphincter of Oddi dysfunction. Gastrointest Endosc Clin N Am 1996;6:117-25. 2. Hogan W, Sherman S, Pasricha P, Cart-Locke DL. Position paper on sphincter of Oddi manometry. Gastrointest Endosc 1997;45:342-8. 3. Geenen JE, Hogan WJ, Dodds WJ, Toouli J, Venu RP. The efficacy of endoscopic sphincterotomy after cholecystectomy in
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D Eversman, E Fogel, M Rusche, et al.
patients with suspected sphincter of Oddi dysfunction. N Engl J Med 1989;320:82-7. 4. Roberts-Thomson IC, Toouli J. Is endoscopic sphincterotomy for disabling biliary-type pain after cholecystectomy effective? Gastrointest Endosc 1985;31:370-3. 5. Sherman S, Troiano FP, Hawes RH, O'Connor KW, Lehman GA. Frequency of abnormal sphincter of Oddi manometry compared with the clinical suspicion of sphincter of Oddi dysfunction. Am J Gastroenterol 1991;86:586-90. 6. Meshinpoor H, Mollot M. Sphincter of Oddi dysfunction and unexplained abdominal pain: clinical and manometric study. Dig Dis Sci 1992;37:257-61. 7. Botoman VA, Kozarek RA, Novel LA, Patterson DJ, Ball TJ, Wechter DG, et al. Long term outcome after endoscopic sphincterotomy in patients with biliary colic and suspected sphincter of Oddi dysfunction. Gastrointest Endosc 1994;40:165-70. 8. Lehman GA, Sherman S. Sphincter of Oddi dysfunction. Int J Pancreatol 1997;20:11-25. 9. Smithline X, Hawes R, Lehman GA. Interobserver variability in interpreting sphincter of Oddi manometry (SOM). Gastrointest Endosc 1993;39:486-91. 10. Guelrud M, Mendoza S, Rossiter G, Villegas MI. Sphincter of Oddi manometry in healthy volunteers. Dig Dis Sci 1990;35: 38-46. 11. Sherman S, Gottlieb K, Uzer MF, Smith MT, Khusro QE, Earle DT, et al. Effects of meperidine on the pancreatic and biliary sphincter. Gastrointest Endosc 1996;44:239-42. 12. Elm GH, Barnett JL. Meperidine need not be prescribed during sphincter of Oddi manometry. Gastrointest Endosc 1994; 40:7-9. 13. Rolny P, Arleback A, Funch-Jensen P, Kruse A, Jarnerot G. Clinical significance of manometric assessment of both pancreatic duct and bile duct sphincter in the same patient. Scand J Gastroenterol 1989;24:751-4. 14. Silverman WB, Ruffolo TA, Sherman S, Hawes RH, Lehman GA. Correlation of basal sphincter pressures measured from both the bile duct and pancreatic duct in patients with suspected sphincter of Oddi dysfunction. Gastrointest Endosc 1992;38:440-3. 15. Raddawi H, Geenen J, Hogan W, Dodds W, Venu R, Johnson G. Pressure measurements from biliary and pancreatic segments of sphincter of Oddi--comparison between patients with abdominal pain, biliary, or pancreatic disease. Dig Dis Sci 1991;36:71-4. 16. Sherman S, Troiano FP, Hawes RH, Lehman GA. Sphincter of Oddi manometry: decreased risk of clinical pancreatitis with the use of a modified aspirating catheter. Gastrointest Endosc 1990;36:462-6. 17. Freeman ML, Nelson DB, Sherman S, Haber GB, Herman ME, Dorsher PJ, et al. Complications of endoscopic biliary sphincterotomy: a prospective, multicenter study. N Engl J Med 1996;335:909-18. 18. Sherman S, Eversman D, Fogel E, Gottlieb K, Earle D. Sphincter of Oddi dysfunction (SOD): needle-knife pancreatobiliary sphincterotomy over pancreatic stent (KNOPS) has a lower post-procedure pancreatitis rate than pull-type biliary sphincterotomy (BES) [abstract]. Gastrointest Endosc 1997; 45:AB148. 19. Tarnasky PR, Palesch Y, Cunningham JT, Cotton PB, Hawes RH. Pancreatic stenting prevents pancreatitis after biliary sphincterotomy in patients with sphincter of Oddi dysfunction: a prospective randomized trial [abstract]. Gastrointest Endosc 1997;45:AB150.
GASTROINTESTINAL ENDOSCOPY 641
Sphincter of Oddi m a n o m e t r y (SOM) may be useful when evaluating patients with idiopathic recurre n t pancreatitis, chronic pancreatitis or unexplained pancreatobiliary-type pain. It is considered by some to be the standard in assessing patients for sphincter of Oddi dysfunction (SOD) and to be helpful in selecting patients who are more likely to respond to sphinct e r ablation. 1-3 The f r equency of a b n o r m a l SOM varies in published series from 7% to 55%. 4-8 Most such studies report m a n o m e t r y dat a for either the pancreatic duct or the bile duct but not both. Some fail to report which duct was studied. To thoroughly assess the sphincter of Oddi, both the pancreatic and
Received March 5, 1999. Accepted July 2, 1999. From the Division of Gastroenterology/Ilepatology, Indiana University Medical Center, Indianapolis, Indiana. Reprint requests: Glen A. Lehman, MD, Division of Gastroenterology/Hepatology, Indiana University Medical Center, 550 N. University Blvd., Suite 2300, Indianapolis, IN 46202. Copyright 9 1999 by the American Society for Gastrointestinal Endoscopy 0016-5107/99/$8.00 + 0 37/1/101233 VOLUME 50, NO. 5, 1999
biliary segments m u s t be evaluated. This stu d y reports the m a n o m e t r y findings in a large series of patients in whom both pancreatic and biliary sphincter pressures were recorded at the same session. PATIENTS AND METHODS
Between 1993 and 1996, 682 patients at our institution underwent ERCP and attempted manometry of both biliary and pancreatic ducts for suspected SOD. Manometry of both ducts was successful in 593 patients who constitute the study population. Patients were excluded if pancreas divisum, bile duct stones, or pancreatobiliary malignancy was found at ERCP. Liver transplant patients were excluded. Patients with chronic pancreatitis by clinical evaluation or ductography were specifically included no matter what the etiology of the disease. The indication for SOM was to evaluate sphincter function in patients with (1) acute recurrent pancreatitis of unknown etiology, (2) acute or recurrent pancreatitis of documented or suspected etiology, (3) chronic pancreatitis of known or unknown etiology, or (4) pancreaticobiliary-type pain, with or without elevated liver or pancreatic enzymes or ductal dilatation on US/CT. GASTROINTESTINAL ENDOSCOPY 637
D Eversman, E Fogel, M Rusche, et al.
Abnormal sphincter manometry and sphincter of Oddi dysfunction
Table 1. Modified Milwaukee classification for possible sphincter of Oddi dysfunction: biliary type Biliary type I Biliary type II Biliary type III
Patients with biliary-type pain, ALT/AST/ALP1.1x normal documented on any occasion, and bile duct >10 mm diameter Patients with biliary-type pain but only one of the above criteria Patients with only biliary-type pain and no other abnormalities
ALT, Alanine aminotransferase; AST, aspartate aminotransferase; ALP, alkaline phosphatase. Ductal drainage times were not evaluated or used in this classification.
Table 2. Modified Milwaukee classification for possible sphincter of Oddi dysfunction: pancreatic type Pancreatic type I
Patients with pancreatic-type pain, amylase or lipase l a x normal documented on any occasion, pancreatic duct >6 mm in the head or >5 mm in body Pancreatic type II Patients with pancreatic-type pain but only one of the above criteria Pancreatic type III Patients with only pancreatic-type pain and no other abnormalities Ductal drainage times were not evaluated or used in this classification Based on clinical, radiographic, and laboratory data, patients were categorized according to a modified classification of SOD (biliary types I, II, III and pancreatic types I, II, III) (Tables 1 and 2). Each patient was classified twice; e.g., type I biliary (with a dilated bile duct) and type III pancreatic with normal caliber pancreatic duct and absence of pancreatic enzyme abnormality. The classification of patients included ERCP data but the determination was made before manometry. Because of this, chronic pancreatitis found only at ERCP would convert a classification of pancreatic type III to pancreatic type II. Fiftyone patients either continued to have symptoms or symptoms recurred after therapy and were studied again. In these cases, the original classification for each patient was maintained throughout the study.
Manometry technique SOM was performed at ERCP in the conventional retrograde fashion using a low-compliance infusion pump with a triple lumen 5F aspirating type catheter (previously described5). One of the three lumens was used to aspirate fluid from the duct to prevent over distention. Duct position was confirmed by aspiration of clear juice from the pancreatic duct or yellow fluid from the bile duct. Contrast media was also injected for diagnostic ductography and to confirm catheter location. The basal sphincter pressure was recorded as the baseline pressure between phasic waves using the duodenal luminal pressure as a zero reference. Recording was sustained a m i n i m u m of 30 seconds, and generally more t h a n 1 minute; pressures were recorded in at least two leads. The four-point method was used to determine the most representative segment for measurement of the basal pressure. 9 The four lowest points in the highest sustained sphincter pressure zone are read and averaged in this method. The mean of all basal sphincter recordings (combining all leads and all pull throughs) was taken as the actual basal sphincter pressure for data analysis. Biliary and pancreatic sphincter data were tallied separately. A basal sphincter pressure greater than or equal to 40 mm Hg was considered abnormal.10 Only basal 638 GASTROINTESTINAL ENDOSCOPY
sphincter pressure was evaluated; phasic wave amplitude and duration were disregarded. Tracings were interpreted on the day they were recorded, strictly as normal or abnormal for each patient. Pancreatic and biliary duct diameters were determined radiographically as follows: the widest diameter of the common bile duct and common hepatic duct were measured and if either was greater than 10 mm in diameter (after correction for magnification) the duct was considered dilated. This classification was used regardless of whether the gallbladder had previously been removed. The pancreatic duct was considered abnormal if the corrected diameter of the main duct in the head was greater than 6 mm or greater t h a n 5 mm when measured in the body. Sedation for m a n o m e t r y was achieved with diazepam alone in 256 patients, and diazepam plus meperidine in 337 patients.ll, 12 When used, meperidine dose was limited to 1 mg/kg or less until SOM was completed. Anticholinergics and other drugs known to affect the sphincter were not administered during ERCP or within 12 hours before the examination.
RESULTS Of the 593 patients who participated in the study, 125 had acute recurrent pancreatitis of unknown etiology, 30 had acute recurrent pancreatitis with a suspected etiology, 26 had chronic pancreatitis, and 412 had pancreatobiliary-type pain. Liver s e r u m chemistries and pancreatic s e r u m e n z y m e s w e r e a s s e s s e d in all p a t i e n t s . C h o l e c y s t e c t o m y h a d b e e n p e r f o r m e d in 402 (67.6%) p a t i e n t s , 231 (39.1%) h a d p r i o r a b l a t i o n of t h e biliary sphincter, a n d 61 (10.2%) h a d p r i o r ablation of the p a n c r e a t i c sphincter.
Patients with intact sphincters Table 3 s h o w s t h e f r e q u e n c y of b a s a l s p h i n c t e r p r e s s u r e a b n o r m a l i t i e s in biliary t y p e s I, II, I I I a n d Table 4 s h o w s s i m i l a r d a t a for p a n c r e a t i c t y p e s I, II, VOLUME 50, NO. 5, 1999
Abnormal sphincter manometry and sphincter of Oddi dysfunction
D Eversman, E Fogel, M Rusche, et al.
Table 3. Frequency of abnormal basal sphincter pressure in patients with intact sphincters Biliary type I
Patient No.
III II I Total
214 123 23 360
Pancreas alone 37 27 4 68
Biliary alone
(17.3%) (22.0%) (17.4%) (18.9%)
23 14 4 41
(10.7%) (11.4%) (17.4%) (11.4%)
Both 67 39 7 113
(31.3%) (31.7%) (30.4%) (31.4%)
Total 127 80 12 219
(59.3%)* (65.0%)* (65.2%)* (60.1%)
*p = Not significant.
Table 4. Frequency of abnormal basal sphincter pressure in patients with intact sphincters Pancreatic type
Patient No.
III II I Total
253 106 1 360
Pancreas alone 45 (17.8%) 23 (21.7%) 0 68 (18.9%)
Biliary alone
Both
33 (13.0%) 8 (7.6%) 0 41 (11.4%)
72 (28.5%) 40 (37.8%) 1 (100.0%) 113 (31.4%)
Total 150 (59.3%)* 71 (67.0%)* 1 (100.0%)* 222 (61.7%)
*p = Not significant.
Table 5. Frequency of abnormal basal sphincter pressure in patients with type II intact sphincters (typed using overall criteria) Patient No. All patients No pancreatitis Idiopathic pancreatitis Chronic pancreatitis
194 136 47 39
Pancreas alone 43 31 12 7
Biliary alone
(22.2%) (15.4%) (25.5%) (17.9%)
18 18 3 3
(9.3%) (13.2%)
(6.4%) (7.7%)
Both 66 37 19 11
(34.0%) (27.2%) (40.4%) (28.2%)
Total 127 76 34 21
(65.5%)a (55.9%)b (72.3%)c (53.9%)d
p < 0.05: a vs. b; b vs. c; c vs. d. p = Not significant: a vs. c; a vs. d; b vs. d.
III. Because the numbers of type I patients in the pancreatic and biliary groups were relatively small, these patients were not sub-categorized. The frequency of abnormalities was nearly identical regardless of which classification (biliary or pancreatic) system was used. Therefore, the data were combined and patients were categorized according to worst parameter (e.g., if the patient was biliary type II and pancreatic type III, then overall type II was the final classification). Classification yielded 194 overall type II patients with intact sphincters and 143 overall type III patients with intact sphincters. To further characterize this group, the presence of idiopathic and chronic pancreatitis was evaluated separately. In the overall type III category, there were 143 patients. This included five patients who had no clinical history of pancreatitis and normal serum enzymes. At their first ERCP, pancreatographic changes consistent with chronic pancreatitis were found. Four of the five (80%) had abnormal basal sphincter manometry; three had both biliary and pancreatic duct abnormalities, and one had isolated elevated biliary basal sphincter pressure. In the other patient manometry of both ducts was normal. Table 5 shows the frequency of abnormal basal sphincter pressures (with intact sphincters) in patients with or without idiopathic and chronic pan~ creatitis classified as overall type II. If a patient had VOLUME 50, NO. 5, 1999
a clinical history suggestive of idiopathic pancreatitis but was found to have chronic pancreatitis by pancreatography, then both categories were used for classification purposes.
Patients with previous sphincter ablation In patients who remained symptomatic or did not have long-term pain relief with sphincter therapy, prior biliary sphincter ablation usually produced normal biliary basal sphincter pressures; however, pancreatic sphincter pressure remained abnormal in more than half of the patients (Table 6). After both sphincters were ablated, 20% of patients still had abnormal pancreatic or biliary sphincter pressure.
Patients with prior cholecystectomy Cholecystectomy had been performed in 402 of 593 patients (67.6%) before ERCP and SOM. In this group, 55.7% of patients had SOD: 24.8% had elevated pancreatic sphincter pressure alone, 8.5% had elevation of the biliary sphincter pressure alone, and 22.4% had elevated pancreatic and biliary sphincter pressures. In the 191 patients with gallbladders, the frequency of SOD was virtually identical at 55%: 28.3% had elevated pancreatic sphincter pressure alone, 4.2% had elevated biliary sphincter pressure alone, and 22.5% had elevated pancreatic and biliary sphincter pressures. GASTROINTESTINAL ENDOSCOPY (}39
D Eversman, E Fogel, M Rusche, et al.
Abnormal sphincter manometry and sphincter of Oddi dysfunction
Table 6. Frequency of abnormal basal sphincter pressure after sphincter ablation Biliary ablated Both ablated Total
Patient No.
Pancreas alone
172 60 232
79 (45.9%) 8 (13.3%) 87 (37.5%)
DISCUSSION Sphincter of Oddi dysfunction is a recognized cause of pancreatitis, cholestasis, and pancreatobiliary-type pain. SOM is now the most commonly used method to evaluate the sphincter for SOD. The frequency of abnormal basal sphincter pressure has varied greatly in reported series which may be a reflection of the patient population assessed, which ductal system was assessed and the criteria used to define the limits of normal. Measurements of both pancreatic and biliary components of the sphincter are necessary to thoroughly evaluate the sphincter mechanism.13-15 Discordance is present if the manometry findings with respect to the biliary duct (normal or abnormal) differ from those for the pancreatic duct. Our data confirm that in previously untreated patients discordance is high. Rolney et al. 13 found that 53% of 17 patients had manometry results that differed (normal versus abnormal) with regard to the distinct sphincter segments. In this present series of 360 previously untreated patients the discordance rate varied from 26% to 35% depending on the patient category assessed. Therefore, the assumption that manometric findings with respect to one duct would be the same for the other would be correct in only 65% to 74% of the cases. Classification systems have been used to identify patients who might require manometry to determine the need for sphincter ablation. These have used clinical data, laboratory tests, radiographic measurements, and ductal drainage time. Routinely, only the bile duct sphincter component has been evaluated. However, our study data show that both ducts should be evaluated. Therefore, it becomes necessary to classify each patient with respect to both the biliary and pancreatic components of the sphincter. This cumbersome method can be abandoned in favor of one overall type; when two types are distinguished there appears to be little difference between them in predicting abnormal basal pressure. A single overall classification would lead to more uniform groupings of patients, thereby making data more applicable in clinical practice. Furthermore, when both sides of the sphincter are evaluated, there is little difference in the frequency of SOD according to the modified Geenen-Hogan classification used in this study. 640
GASTROINTESTINAL ENDOSCOPY
Biliary alone 1 (0.6%) 0 1 (0.43%)
Both
Total
16 (9.3%) 4 (6.7%) 20 (8.6%)
96 (55.8%) 12 (20.0%) 108 (46.6%)
The frequency at which sphincter abnormalities are detected is a major factor in determining the utility of SOM. The frequency of abnormal biliary manometry has been reported to vary from 28% to 60% for biliary type II patients. The frequency in biliary type III patients has varied more markedly from 7% to 55%. This wide variance has not been helpful in deciding whether to use manometry in patients who have pain as the only manifestation of possible SOD. Risk-to-benefit ratio is another major determinant of the utility of SOM. The study of Freeman et alJ 7 found similar complication rates for endoscopic sphincterotomy in patients with documented versus suspected SOD. The complication rate was 21% for patients who underwent manometry and 25% for those who did not have preceding manometry. This suggests that the high complication rates are intrinsic to the study group and the therapy applied rather than the manometry itself. 17 Routine use of pancreatic stents during sphincterotomy has been shown to decrease the pancreatitis rates in preliminary studiesJS, 19 In this study the frequency of SOD was high in patients with idiopathic pancreatitis (72.3%) and chronic pancreatitis (53.9%). Elevated basal sphincter pressure has long been accepted as a potential etiology in patients with idiopathic pancreatitis. The increased incidence of SOD in this group, compared with that of earlier studies, reflects the importance of evaluating both the pancreatic and biliary sphincter components. With regard to the association between SOD and chronic pancreatitis, it is unclear whether generalized scarring also involves the sphincter mechanism, leading to SOD, or the hypertensive sphincter causes elevated pressure upstream leading to morphologic changes. At present, this association between chronic pancreatitis and SOD appears to warrant further research. It is not suggested that SOM be considered part of the routine evaluation of patients with chronic pancreatitis. There are several plausible explanations for the marked differences in frequencies of basal sphincter pressure abnormalities in the various published s e r i e s . 7,14,15 First, selection of patients with a pain pattern that is typical of biliary tract disease versus a nonspecific pattern as might be seen with the irritable bowel syndrome will probably increase the VOLUME 50, NO. 5, 1999
Abnormal sphincter manometry and sphincter of Oddi dysfunction
percentage of patients with SOD. Second, if abnormal sphincter pressure is required in two or three recording channels to make the diagnosis of SOD, as opposed to the mean of all channels, then the frequency of SOD will be lower. The use of different equipment in these studies (e.g., Arndorfer catheter versus a triple-lumen aspiration catheter) may also be a factor, but this is difficult to quantify. Third, assessment of only one sphincter component versus both will lower the observed frequency of SOD. With assessment of only one component, the frequency of SOD may be higher in type II patients (i.e., abnormal SOM in patients with elevated liver function tests) than type III patients, a difference which may not be evident with performance of dual sphincter manometry. After biliary ablative therapy the vast majority of patients had normal biliary sphincter pressure, even if still symptomatic (the reason for repeating the study). However, a high percentage of these symptomatic patients will have abnormal residual pancreatic sphincter pressure. This raises the question whether patients with both pancreatic and biliary sphincter pressure abnormalities should be treated with biliary sphincterotomy alone. We are conducting retrospective and prospective studies to determine the frequency of pain relief with biliary versus combined pancreatobiliary sphincterotomy in these groups of patients. This large series confirms that abnormalities occur in both pancreatic and biliary segments of the sphincter of Oddi in highly symptomatic patients. Measuring sphincter pressure in both segments is necessary to determine the full extent of SOD. Patients with idiopathic pancreatitis and those with chronic pancreatitis appear to have abnormal sphincter pressures as often as those without pancreatitis. A single classification of patients based on the worst parameter appears to have the same utility as a double classification based on measurements from each segment of the sphincter. Further studies are needed to determine the optimal thera9 py for patients in whom both sphincters are abnormal as well as those with isolated pancreatic sphincter abnormalities. REFERENCES 1. Kalloo AN, Pasricha PJ. Therapy of sphincter of Oddi dysfunction. Gastrointest Endosc Clin N Am 1996;6:117-25. 2. Hogan W, Sherman S, Pasricha P, Cart-Locke DL. Position paper on sphincter of Oddi manometry. Gastrointest Endosc 1997;45:342-8. 3. Geenen JE, Hogan WJ, Dodds WJ, Toouli J, Venu RP. The efficacy of endoscopic sphincterotomy after cholecystectomy in
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patients with suspected sphincter of Oddi dysfunction. N Engl J Med 1989;320:82-7. 4. Roberts-Thomson IC, Toouli J. Is endoscopic sphincterotomy for disabling biliary-type pain after cholecystectomy effective? Gastrointest Endosc 1985;31:370-3. 5. Sherman S, Troiano FP, Hawes RH, O'Connor KW, Lehman GA. Frequency of abnormal sphincter of Oddi manometry compared with the clinical suspicion of sphincter of Oddi dysfunction. Am J Gastroenterol 1991;86:586-90. 6. Meshinpoor H, Mollot M. Sphincter of Oddi dysfunction and unexplained abdominal pain: clinical and manometric study. Dig Dis Sci 1992;37:257-61. 7. Botoman VA, Kozarek RA, Novel LA, Patterson DJ, Ball TJ, Wechter DG, et al. Long term outcome after endoscopic sphincterotomy in patients with biliary colic and suspected sphincter of Oddi dysfunction. Gastrointest Endosc 1994;40:165-70. 8. Lehman GA, Sherman S. Sphincter of Oddi dysfunction. Int J Pancreatol 1997;20:11-25. 9. Smithline X, Hawes R, Lehman GA. Interobserver variability in interpreting sphincter of Oddi manometry (SOM). Gastrointest Endosc 1993;39:486-91. 10. Guelrud M, Mendoza S, Rossiter G, Villegas MI. Sphincter of Oddi manometry in healthy volunteers. Dig Dis Sci 1990;35: 38-46. 11. Sherman S, Gottlieb K, Uzer MF, Smith MT, Khusro QE, Earle DT, et al. Effects of meperidine on the pancreatic and biliary sphincter. Gastrointest Endosc 1996;44:239-42. 12. Elm GH, Barnett JL. Meperidine need not be prescribed during sphincter of Oddi manometry. Gastrointest Endosc 1994; 40:7-9. 13. Rolny P, Arleback A, Funch-Jensen P, Kruse A, Jarnerot G. Clinical significance of manometric assessment of both pancreatic duct and bile duct sphincter in the same patient. Scand J Gastroenterol 1989;24:751-4. 14. Silverman WB, Ruffolo TA, Sherman S, Hawes RH, Lehman GA. Correlation of basal sphincter pressures measured from both the bile duct and pancreatic duct in patients with suspected sphincter of Oddi dysfunction. Gastrointest Endosc 1992;38:440-3. 15. Raddawi H, Geenen J, Hogan W, Dodds W, Venu R, Johnson G. Pressure measurements from biliary and pancreatic segments of sphincter of Oddi--comparison between patients with abdominal pain, biliary, or pancreatic disease. Dig Dis Sci 1991;36:71-4. 16. Sherman S, Troiano FP, Hawes RH, Lehman GA. Sphincter of Oddi manometry: decreased risk of clinical pancreatitis with the use of a modified aspirating catheter. Gastrointest Endosc 1990;36:462-6. 17. Freeman ML, Nelson DB, Sherman S, Haber GB, Herman ME, Dorsher PJ, et al. Complications of endoscopic biliary sphincterotomy: a prospective, multicenter study. N Engl J Med 1996;335:909-18. 18. Sherman S, Eversman D, Fogel E, Gottlieb K, Earle D. Sphincter of Oddi dysfunction (SOD): needle-knife pancreatobiliary sphincterotomy over pancreatic stent (KNOPS) has a lower post-procedure pancreatitis rate than pull-type biliary sphincterotomy (BES) [abstract]. Gastrointest Endosc 1997; 45:AB148. 19. Tarnasky PR, Palesch Y, Cunningham JT, Cotton PB, Hawes RH. Pancreatic stenting prevents pancreatitis after biliary sphincterotomy in patients with sphincter of Oddi dysfunction: a prospective randomized trial [abstract]. Gastrointest Endosc 1997;45:AB150.
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