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Usefulness of endoscopic ultrasonography in patients with “idiopathic” acute pancreatitis
Usefulness of Endoscopic Ultrasonography in Patients with “Idiopathic” Acute Pancreatitis Jean Louis Frossard, MD, Luis Sosa-Valencia, MD, Gilles Amouyal, MD, Olivier Marty, MD, Antoine Hadengue, MD, Paul Amouyal, MD PURPOSE: No underlying cause is found in as many as 30% of patients with acute pancreatitis. The aim of this study was to evaluate the usefulness of endoscopic ultrasonography in the diagnosis of biliary tract pathology or chronic pancreatitis in these patients. SUBJECTS AND METHODS: We evaluated 168 patients who were referred with idiopathic pancreatitis. Diagnoses obtained by endoscopic ultrasonography were prospectively compared with those obtained at surgery in 101 patients, by endoscopic cholangiopancreatography in 49 patients, or by bile crystal analysis and medical follow-up in 18 patients.
RESULTS: Endoscopic ultrasonography was abnormal in 135 (80%) patients, 124 of whom had biliary tract disease. When the results of endoscopic ultrasonography were compared with those made after multidisciplinary investigations, endoscopic ultrasonography correctly identified the cause—most commonly biliary tract disease— of the “idiopathic” pancreatitis in 155 (92%) of the 168 patients. CONCLUSIONS: Endoscopic ultrasonography is valuable in determining the cause of acute pancreatitis in patients initially considered to have idiopathic pancreatitis. Am J Med. 2000; 109:196 –200. 䉷2000 by Excerpta Medica, Inc.
T
sonography is one of the most accurate techniques for the detection of pancreatic masses such as pancreatic carcinoma (18,19). In patients with chronic pancreatitis, endoscopic ultrasonography can detect changes in the parenchyma and ducts (20,21). Endoscopic ultrasonography is also useful for detecting microlithiasis in the gallbladder and biliary sludge (22,23). The present study evaluated the usefulness of endoscopic ultrasonography among patients with acute pancreatitis in whom conventional ultrasonography of the upper abdomen was negative. The performance of endoscopic ultrasonography was compared with the results of a multidisciplinary diagnostic approach, including endoscopic retrograde cholangiopancreatography, bile crystal analysis, laparoscopic or conventional cholecystectomy associated with a histologic analysis of the gallbladder, and pancreatic surgery.
he most common causes of acute pancreatitis are excessive use of alcohol and gallstone disease. Hypertriglyceridemia, hypercalcemia, drugs, pancreatic cancer, and infections are other known causes (1– 3). Although the microscopic examination of bile can be used to assess whether pancreatitis has a biliary origin (4 – 6), the sensitivity of this method is only 67% to 87% (7–11), depending on where the bile is sampled. After a thorough clinical investigation, however, 20% to 30% of patients with acute pancreatitis have no identifiable cause and are given the diagnosis of idiopathic pancreatitis (3,4). Recent advances in defining genetic causes of acute pancreatitis—such as a mutation in the cationic trypsinogen gene (12) and mutations in the cystic fibrosis transmembrane conductance regulator gene (13)—may decrease this proportion in the future. Endoscopic retrograde cholangiopancreatography serves as the gold standard for imaging procedures used in the diagnosis and management of biliary tract diseases and chronic pancreatitis (14), but it is associated with a substantial risk of complications, especially in patients with recurrent pancreatitis (15). A newer imaging technique— endoscopic ultrasonography— can provide high-resolution images of the gastrointestinal and biliary tracts (16,17). It uses higher frequencies than conventional abdominal ultrasound, and the image quality is not compromised by gas in the intestine. Endoscopic ultraFrom the Division of Gastroenterology (JLF, AH), University Hospital, Geneva, Switzerland, and the Gastro-Louvre (LSV, GA, OM, PA), Paris, France. Requests for reprints should be addressed to Jean Louis Frossard, MD, Division of Gastroenterology, Geneva University Hospital, Rue Micheli du Crest, 1211 Gene`ve 14 Switzerland. Manuscript submitted August 9, 1999, and accepted in revised form May 1, 2000. 196
䉷2000 by Excerpta Medica, Inc. All rights reserved.
PATIENTS AND METHODS From January 1991 to December 1995, 168 patients (102 [61%] men, mean [⫾ SD] age of 50 ⫾ 15 years, range 10 to 84) with acute pancreatitis of unknown cause (idiopathic pancreatitis) who were seen at the Gastro-Louvre in Paris, France, were included in this study. Patients who had usually been hospitalized in other hospitals in Paris were referred to our center because of our expertise in endoscopic ultrasonography. Complete medical histories, emphasizing use of alcohol, were obtained. The diagnosis of acute pancreatitis was defined as the presence of acute epigastric pain associated with serum amylase or lipase concentrations that were at least three times greater than the upper limit of normal (24,25) and an abdominal ultrasound examination that showed pancreatic inflam0002-9343/00/$–see front matter PII S0002-9343(00)00478-2
Endoscopic Ultrasonography for “Idiopathic” Acute Pancreatitis/Frossard et al
mation. The diagnosis of idiopathic pancreatitis was considered only if there was no history of alcohol abuse (⬍60 g per day for men and ⬍40 g per day for women), no previous history of biliary disease, no recent surgery, no use of drugs that are known to cause pancreatitis, no metabolic diseases such as hypercalcemia or hyperlipemia, and no evidence of biliary or pancreatic carcinoma, gallbladder microlithiasis, or biliary sludge identified by conventional ultrasonography. Patients with elevated serum gamma glutamyltransferase or aminotransferase levels were not excluded. All patients underwent one or more conventional (abdominal) ultrasound examinations performed by experienced radiologists within 1 week of the onset of symptoms. Among the 168 patients with acute pancreatitis, 153 (91%) cases were classified as mild and 15 (9%) as severe by Ranson’s score (26). At our center, all patients underwent endoscopic ultrasonography (GFUM 3/EUM and GFUM 20/EUM 20, Olympus, France). Patients were sedated with midazolam and propofol. Endoscopic ultrasonography was performed to study the gallbladder, the cystic and the common bile ducts, and the pancreas (16,17). Microlithiasis was defined as a hyperechoic signal of 0.5 mm to 2 mm without a postacoustic shadow. Biliary sludge was defined as moving echoes of low amplitude in the lumen of the gallbladder without any postacoustic shadow. Gallstones were defined as echoes of high amplitude with a postacoustic shadow ⬎2 mm. The criteria for chronic pancreatitis were the following: (1) echogenic duct walls, (2) irregular duct contour, (3) dilated side branches, (4) ductal stones, (5) parenchymal inhomogeneity, (6) parenchyma echogenic foci, (7) parenchyma echogenic strands, and (8) lobularity of the gland (27–29). Patients with three or more criteria were considered to have chronic pancreatitis. When only one or two criteria were present, the diagnosis of possible early chronic pancreatitis was made (30). Additional studies were performed subsequently to confirm the diagnosis, including bile crystal analysis of fresh samples collected during an esophogogastroduodenoscopy, endoscopic cholangiopancreatography, cholecystectomy, or pancreatic surgery. The choice of these procedures was made by the attending physician and the patient. If endoscopic ultrasonography showed cholelithiasis, patients usually underwent surgery, whereas if surgery was not indicated, patients had an endoscopic cholangiopancreatography with a sphincterotomy. If endoscopic ultrasonography showed a common bile duct stone, endoscopic cholangiopancreatography with a sphincterotomy was performed, followed by cholecystectomy. If endoscopic cholangiopancreatography did not detect biliary tract disease, bile crystal analysis was performed. When evidence of chronic pancreatitis was detected by endoscopic
Table 1. Comparison between the Initial Diagnosis after Endoscopic Ultrasound and Final Diagnosis after Multidisciplinary Investigation
Diagnosis
Initial Endoscopic Ultrasound Diagnosis
Final Diagnosis
Number (Percent) Biliary stones, microlithiasis, sludge Chronic pancreatitis Pancreatic cancer Pancreatic intraductal mucin-producing tumor Ampulloma Choledocal cyst Other Idiopathic acute pancreatitis Total
103 (62)
99 (59)
16 (10) 4 (2) 4 (2)
17 (10) 3 (2) 3 (2)
3 (2) 1 (1)
3 (2) 1 (1) 4 (2)* 38 (23) 168
37 (21)† 168
* Includes 1 patient with drug-induced acute pancreatitis and 1 patient with pancreatitis due to a viral infection. † Includes 4 patients with morphologic changes of the pancreas due to the recent attack of pancreatitis without obvious origin (enlargement of the gland).
ultrasonography, the diagnosis was confirmed with endoscopic cholangiopancreatography, using the Cambridge criteria (14). If none of these procedures produced a definitive diagnosis, patients received medical followup.
RESULTS Endoscopic ultrasonography was performed a mean of 18 ⫾ 13 days (range 10 to 180) after the onset of the clinical event. Results were abnormal in 135 (80%) of the 168 patients and suggested a cause for the pancreatitis in 131 patients (Table 1). Biliary tract disease was found in 103 (61%) patients, including 52 (50%) patients with gallstones or microlithiasis (Figures 1 and 2), 12 (12%) with gallbladder sludge (Figure 3), and 10 (10%) with common bile duct stones; 29 (28%) additional patients had a combination of these findings. Twelve patients met the criteria for chronic pancreatitis (Figure 4); 4 others were diagnosed with possible early chronic pancreatitis. Endoscopic ultrasonography identified 4 patients with pancreatic cancers that were too small to be seen with conventional ultrasonography. Four patients who had only morphologic changes consistent with acute pancreatitis, and the remaining 33 (20%) patients in whom endoscopic ultrasonography was normal, were given a tentative diagnosis of idiopathic acute pancreatitis. To verify the diagnoses made with endoscopic ultrasonography, patients underwent additional diagnostic
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Figure 1. Endoscopic ultrasonographic image of a small stone (upper arrow) within the gallbladder that was not detected by conventional ultrasound. Gallstones of such size are usually accompanied by a postacoustic shadow (lower arrow).
Figure 3. Endoscopic ultrasonographic image of gallbladder sludge (S). The arrows show the limit of the sludge within the lumen of the gallbladder.
procedures (Table 2). A definitive diagnosis was made at surgery in 101 (60%) patients, by endoscopic cholangiopancreatography in 49 (29%) patients, and by bile crystal analysis in 3 (2%) patients. In the remaining 15 (9%) patients, all of whom had negative bile crystal analysis, the final diagnosis was made after a mean of 25 ⫾ 16 months (range 6 to 60) of follow-up. Medical follow-up identified 2 patients with acute pancreatitis related to viral infection (Coxsackie virus) and 1 patient with furo-
semide-induced acute pancreatitis. Among the 16 patients who had chronic pancreatitis diagnosed with endoscopic ultrasonography, 10 had abnormalities of grade 2 or greater and 6 had abnormalities of grade 1 seen at endoscopic cholangiopancreatography (according to the Cambridge classification). In 13 (8%) patients, the results of endoscopic ultra-
Figure 2. Endoscopic ultrasonographic image of microlithiasis (arrows) within the gallbladder that was not detected by conventional percutaneous ultrasound. Microlithiasis is a hyperechoic signal without postacoustic shadow.
Figure 4. Endoscopic ultrasonographic image of pancreatic echogenic foci that represent calcifications (C) within the head of the pancreas. This finding is one of the main criteria for the diagnosis of chronic pancreatitis.
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Table 2. Results of the Multidisciplinary Investigations in Patients with “Idiopathic” Pancreatitis
Diagnosis
Endoscopic Cholangiography
Surgery
Medical Follow-Up and Bile Crystal Analysis
Total
Number (Percent) Biliary stones Chronic pancreatitis Pancreatic cancer Pancreatic intraductal mucin-producing tumor Ampulloma Choledocal cyst Other Idiopathic acute pancreatitis Total
87 (86) 1 (1) 2 (2)
8 (17) 16 (33)
4 (22) 1 (5)
3 (6) 3 (6) 1 (1) 10 (10) 101
4 (22) 10 (56) 18
19 (39) 49
sonography and the final diagnosis disagreed. Five of these patients, who had a normal endoscopic ultrasonographic examination and had been given a tentative diagnosis of idiopathic pancreatitis, had biliary stones demonstrated at surgery or bile crystal analysis. One patient who was diagnosed at endoscopic ultrasonography with a biliary stone had a choledocal cyst at the time of surgery, and 1 patient diagnosed with pancreatic cancer had focal chronic pancreatitis at surgery. Finally, endoscopic ultrasonography misdiagnosed 5 patients as having biliary stones and 1 patient as having pancreatic intraductal tumor in whom the final diagnosis was idiopathic pancreatitis (diagnosed by surgery [5 patients] or endoscopic cholangiopancreatography [1 patient]). When the results of endoscopic ultrasonography were compared with those of the additional studies, considered as the gold standard in our study, endoscopic ultrasound identified the correct cause of acute pancreatitis in 155 (92%) of the 168 patients, including 123 (95%) of the 130 patients in whom a definite cause of pancreatitis was established, and 32 (84%) of the 38 patients with a final diagnosis of idiopathic pancreatitis. In our study group, the cause of acute pancreatitis was determined in 130 (77%) patients; the remaining 38 (23%) patients were considered to have idiopathic pancreatitis.
DISCUSSION The diagnosis of idiopathic acute pancreatitis is timeconsuming, usually expensive, and may expose a patient to substantial morbidity from diagnostic tests (31). Endoscopic cholangiopancreatography, for example, is associated with a 5% to 6% morbidity rate (31–33) and may induce acute pancreatitis in patients with recurrent pancreatitis and undiagnosed dyskinesia of the sphincter of Oddi (34). Bile crystal analysis is difficult to perform, and
99 (59) 17 (10) 3 (2) 3 (2) 3 (2) 1 (1) 4 (2) 39 (22) 168
its usefulness depends on the location of bile collection (6 –10). Endoscopic ultrasonography can diagnose the cause of extrahepatic cholestasis (35) and is considered to be the endoscopic procedure of choice for visualizing the pancreas (14,16 –19). The positive predictive value of endoscopic ultrasonography for biliary tract disease is about 98% (15), and the procedure has few complications. In the present study, endoscopic ultrasonography correctly identified a cause of acute pancreatitis in 155 of the 168 patients in whom a cause was found by a multidisciplinary diagnostic approach, compared with only 19 of 38 patients in a previous study (27). Our findings support previous studies in which endoscopic ultrasonography was more sensitive and specific for detecting cholelithiasis than was conventional ultrasonography (36 –38). Understanding the cause of pancreatitis can modify a patient’s management and influence prognosis. When a biliary cause is identified and treated, the risk of recurrent pancreatitis is decreased. In recurrent pancreatitis without a known cause, prophylactic cholecystectomy—although sometimes performed— does not affect the recurrence rate (39). Indeed, in our study, 3 patients who underwent cholecystectomy had another attack of pancreatitis. In addition, endoscopic ultrasonography was able to diagnose pancreatic cancer, ampulloma, and intraductal mucin-producing tumors, which may manifest as acute pancreatitis. Thus, our results suggest that endoscopic ultrasonography is a valuable diagnostic tool for the management of patients with acute pancreatitis of unknown origin.
REFERENCES 1. Steer ML. Pathogenesis of acute pancreatitis. Digestion. 1997;58: 46 – 49. 2. Kelly TR. Gallstone pancreatitis: physiopathology. Surgery. 1976; 80:488 – 492.
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22. Dahan P, Andat C, Levy P, et al. Prospective evaluation of endoscopic ultrasonography and microscopic examination of duodenal bile in the diagnosis of cholecystolithiasis in 45 patients with normal conventional ultrasonography. Gut. 1996;38:277–281. 23. Dille JE. Symptom resolution or relief after cholecystectomy correlates strongly with positive combined endoscopic ultrasound and stimulated biliary drainage. Endoscopy. 1997;29:646 – 648. 24. Bradley EL. A clinically based classification system for acute pancreatitis. Arch Surg. 1993;128:586 –590. 25. Sarner M, Cotton PB. Classification of pancreatitis. Gut. 1984;25: 756 –759. 26. Ranson JHC, Rifkind KM, Roses DF, et al. Prognostic signs and the role of operative management in acute pancreatitis. Surg Gynecol Obstet. 1974;139:69 – 81. 27. Catalano MF, Lahoti S, Geenen JE, et al. Prospective evaluation of endoscopic ultrasonography, endoscopic retrograde pancreatography, and secretin test in the diagnosis of chronic pancreatitis. Gastrointest Endosc. 1998;48:11–17. 28. Dancygier H. Endoscopic ultrasonography in chronic pancreatitis. Gastrointest Endosc Clin North Am. 1995;5:795– 804. 29. Wiersema MJ, Hawes RH, Lehman GA, et al. Prospective evaluation of endoscopic ultrasonography and endoscopic retrograde cholangiopancreatography in patients with chronic abdominal pain of suspected pancreatic origin. Endoscopy. 1993;25:555–564. 30. Wiersema MJ, Wiersema LM. Endosonography of the pancreas: normal variation versus changes of early chronic pancreatitis. Gastrointest Endosc Clin North Am. 1995;5:487– 496. 31. Lee MJ, Choi TK, Lai ECS. Endoscopic retrograde cholangiopancreatography after acute pancreatitis. Surg Gynecol Obst. 1986;163: 354 –358. 32. Goodman AJ, Neoptolemos JP, Carr-Locke DL, et al. Detection of gallstones after acute pancreatitis. Gut. 1985;26:125–135. 33. Hamilton I, Bradley P, Lintott DJ, et al. Endoscopic retrograde cholangiopancreatography in the investigation and management of patients after acute pancreatitis. Br J Surg. 1982;69:504 –506. 34. Scicchitano J, Saccone GT, Baker RA, et al. How safe is endoscopic sphincter of Oddi manometry? J Gastroenterol Hepatol. 1995;10: 334 –336. 35. Amouyal P, Palazzo L, Amouyal G, et al. Endosonography. Promising method for diagnosis of extrahepatic cholestasis. Lancet. 1989; 18:1195–1198. 36. Buscail L, Escourrou J, Moreau J, et al. Endoscopic ultrasonography in chronic pancreatitis: a comparative prospective study with conventional ultrasonography, computed tomography and ERCP. Pancreas. 1995;10:251–257. 37. Chak A, Hawes RH, Cooper GS, et al. Prospective assessment of the utility of EUS in the evaluation of gallstone pancreatitis. Gastrointest Endosc. 1999;49:599 – 604. 38. Liu CL, Lo CM, Chan JK, et al. EUS for detection of occult cholelithiasis in patients with idiopathic pancreatitis. Gastrointest Endosc. 2000;51:28 –32. 39. Moreau JA, Zinsmeister AR, Melton LJ, et al. Gallstone pancreatitis and the effect of cholecystectomy: a population-based cohort study. Mayo Clin Proc. 1988;63:466 – 473.
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RESULTS: Endoscopic ultrasonography was abnormal in 135 (80%) patients, 124 of whom had biliary tract disease. When the results of endoscopic ultrasonography were compared with those made after multidisciplinary investigations, endoscopic ultrasonography correctly identified the cause—most commonly biliary tract disease— of the “idiopathic” pancreatitis in 155 (92%) of the 168 patients. CONCLUSIONS: Endoscopic ultrasonography is valuable in determining the cause of acute pancreatitis in patients initially considered to have idiopathic pancreatitis. Am J Med. 2000; 109:196 –200. 䉷2000 by Excerpta Medica, Inc.
T
sonography is one of the most accurate techniques for the detection of pancreatic masses such as pancreatic carcinoma (18,19). In patients with chronic pancreatitis, endoscopic ultrasonography can detect changes in the parenchyma and ducts (20,21). Endoscopic ultrasonography is also useful for detecting microlithiasis in the gallbladder and biliary sludge (22,23). The present study evaluated the usefulness of endoscopic ultrasonography among patients with acute pancreatitis in whom conventional ultrasonography of the upper abdomen was negative. The performance of endoscopic ultrasonography was compared with the results of a multidisciplinary diagnostic approach, including endoscopic retrograde cholangiopancreatography, bile crystal analysis, laparoscopic or conventional cholecystectomy associated with a histologic analysis of the gallbladder, and pancreatic surgery.
he most common causes of acute pancreatitis are excessive use of alcohol and gallstone disease. Hypertriglyceridemia, hypercalcemia, drugs, pancreatic cancer, and infections are other known causes (1– 3). Although the microscopic examination of bile can be used to assess whether pancreatitis has a biliary origin (4 – 6), the sensitivity of this method is only 67% to 87% (7–11), depending on where the bile is sampled. After a thorough clinical investigation, however, 20% to 30% of patients with acute pancreatitis have no identifiable cause and are given the diagnosis of idiopathic pancreatitis (3,4). Recent advances in defining genetic causes of acute pancreatitis—such as a mutation in the cationic trypsinogen gene (12) and mutations in the cystic fibrosis transmembrane conductance regulator gene (13)—may decrease this proportion in the future. Endoscopic retrograde cholangiopancreatography serves as the gold standard for imaging procedures used in the diagnosis and management of biliary tract diseases and chronic pancreatitis (14), but it is associated with a substantial risk of complications, especially in patients with recurrent pancreatitis (15). A newer imaging technique— endoscopic ultrasonography— can provide high-resolution images of the gastrointestinal and biliary tracts (16,17). It uses higher frequencies than conventional abdominal ultrasound, and the image quality is not compromised by gas in the intestine. Endoscopic ultraFrom the Division of Gastroenterology (JLF, AH), University Hospital, Geneva, Switzerland, and the Gastro-Louvre (LSV, GA, OM, PA), Paris, France. Requests for reprints should be addressed to Jean Louis Frossard, MD, Division of Gastroenterology, Geneva University Hospital, Rue Micheli du Crest, 1211 Gene`ve 14 Switzerland. Manuscript submitted August 9, 1999, and accepted in revised form May 1, 2000. 196
䉷2000 by Excerpta Medica, Inc. All rights reserved.
PATIENTS AND METHODS From January 1991 to December 1995, 168 patients (102 [61%] men, mean [⫾ SD] age of 50 ⫾ 15 years, range 10 to 84) with acute pancreatitis of unknown cause (idiopathic pancreatitis) who were seen at the Gastro-Louvre in Paris, France, were included in this study. Patients who had usually been hospitalized in other hospitals in Paris were referred to our center because of our expertise in endoscopic ultrasonography. Complete medical histories, emphasizing use of alcohol, were obtained. The diagnosis of acute pancreatitis was defined as the presence of acute epigastric pain associated with serum amylase or lipase concentrations that were at least three times greater than the upper limit of normal (24,25) and an abdominal ultrasound examination that showed pancreatic inflam0002-9343/00/$–see front matter PII S0002-9343(00)00478-2
Endoscopic Ultrasonography for “Idiopathic” Acute Pancreatitis/Frossard et al
mation. The diagnosis of idiopathic pancreatitis was considered only if there was no history of alcohol abuse (⬍60 g per day for men and ⬍40 g per day for women), no previous history of biliary disease, no recent surgery, no use of drugs that are known to cause pancreatitis, no metabolic diseases such as hypercalcemia or hyperlipemia, and no evidence of biliary or pancreatic carcinoma, gallbladder microlithiasis, or biliary sludge identified by conventional ultrasonography. Patients with elevated serum gamma glutamyltransferase or aminotransferase levels were not excluded. All patients underwent one or more conventional (abdominal) ultrasound examinations performed by experienced radiologists within 1 week of the onset of symptoms. Among the 168 patients with acute pancreatitis, 153 (91%) cases were classified as mild and 15 (9%) as severe by Ranson’s score (26). At our center, all patients underwent endoscopic ultrasonography (GFUM 3/EUM and GFUM 20/EUM 20, Olympus, France). Patients were sedated with midazolam and propofol. Endoscopic ultrasonography was performed to study the gallbladder, the cystic and the common bile ducts, and the pancreas (16,17). Microlithiasis was defined as a hyperechoic signal of 0.5 mm to 2 mm without a postacoustic shadow. Biliary sludge was defined as moving echoes of low amplitude in the lumen of the gallbladder without any postacoustic shadow. Gallstones were defined as echoes of high amplitude with a postacoustic shadow ⬎2 mm. The criteria for chronic pancreatitis were the following: (1) echogenic duct walls, (2) irregular duct contour, (3) dilated side branches, (4) ductal stones, (5) parenchymal inhomogeneity, (6) parenchyma echogenic foci, (7) parenchyma echogenic strands, and (8) lobularity of the gland (27–29). Patients with three or more criteria were considered to have chronic pancreatitis. When only one or two criteria were present, the diagnosis of possible early chronic pancreatitis was made (30). Additional studies were performed subsequently to confirm the diagnosis, including bile crystal analysis of fresh samples collected during an esophogogastroduodenoscopy, endoscopic cholangiopancreatography, cholecystectomy, or pancreatic surgery. The choice of these procedures was made by the attending physician and the patient. If endoscopic ultrasonography showed cholelithiasis, patients usually underwent surgery, whereas if surgery was not indicated, patients had an endoscopic cholangiopancreatography with a sphincterotomy. If endoscopic ultrasonography showed a common bile duct stone, endoscopic cholangiopancreatography with a sphincterotomy was performed, followed by cholecystectomy. If endoscopic cholangiopancreatography did not detect biliary tract disease, bile crystal analysis was performed. When evidence of chronic pancreatitis was detected by endoscopic
Table 1. Comparison between the Initial Diagnosis after Endoscopic Ultrasound and Final Diagnosis after Multidisciplinary Investigation
Diagnosis
Initial Endoscopic Ultrasound Diagnosis
Final Diagnosis
Number (Percent) Biliary stones, microlithiasis, sludge Chronic pancreatitis Pancreatic cancer Pancreatic intraductal mucin-producing tumor Ampulloma Choledocal cyst Other Idiopathic acute pancreatitis Total
103 (62)
99 (59)
16 (10) 4 (2) 4 (2)
17 (10) 3 (2) 3 (2)
3 (2) 1 (1)
3 (2) 1 (1) 4 (2)* 38 (23) 168
37 (21)† 168
* Includes 1 patient with drug-induced acute pancreatitis and 1 patient with pancreatitis due to a viral infection. † Includes 4 patients with morphologic changes of the pancreas due to the recent attack of pancreatitis without obvious origin (enlargement of the gland).
ultrasonography, the diagnosis was confirmed with endoscopic cholangiopancreatography, using the Cambridge criteria (14). If none of these procedures produced a definitive diagnosis, patients received medical followup.
RESULTS Endoscopic ultrasonography was performed a mean of 18 ⫾ 13 days (range 10 to 180) after the onset of the clinical event. Results were abnormal in 135 (80%) of the 168 patients and suggested a cause for the pancreatitis in 131 patients (Table 1). Biliary tract disease was found in 103 (61%) patients, including 52 (50%) patients with gallstones or microlithiasis (Figures 1 and 2), 12 (12%) with gallbladder sludge (Figure 3), and 10 (10%) with common bile duct stones; 29 (28%) additional patients had a combination of these findings. Twelve patients met the criteria for chronic pancreatitis (Figure 4); 4 others were diagnosed with possible early chronic pancreatitis. Endoscopic ultrasonography identified 4 patients with pancreatic cancers that were too small to be seen with conventional ultrasonography. Four patients who had only morphologic changes consistent with acute pancreatitis, and the remaining 33 (20%) patients in whom endoscopic ultrasonography was normal, were given a tentative diagnosis of idiopathic acute pancreatitis. To verify the diagnoses made with endoscopic ultrasonography, patients underwent additional diagnostic
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Endoscopic Ultrasonography for “Idiopathic” Acute Pancreatitis/Frossard et al
Figure 1. Endoscopic ultrasonographic image of a small stone (upper arrow) within the gallbladder that was not detected by conventional ultrasound. Gallstones of such size are usually accompanied by a postacoustic shadow (lower arrow).
Figure 3. Endoscopic ultrasonographic image of gallbladder sludge (S). The arrows show the limit of the sludge within the lumen of the gallbladder.
procedures (Table 2). A definitive diagnosis was made at surgery in 101 (60%) patients, by endoscopic cholangiopancreatography in 49 (29%) patients, and by bile crystal analysis in 3 (2%) patients. In the remaining 15 (9%) patients, all of whom had negative bile crystal analysis, the final diagnosis was made after a mean of 25 ⫾ 16 months (range 6 to 60) of follow-up. Medical follow-up identified 2 patients with acute pancreatitis related to viral infection (Coxsackie virus) and 1 patient with furo-
semide-induced acute pancreatitis. Among the 16 patients who had chronic pancreatitis diagnosed with endoscopic ultrasonography, 10 had abnormalities of grade 2 or greater and 6 had abnormalities of grade 1 seen at endoscopic cholangiopancreatography (according to the Cambridge classification). In 13 (8%) patients, the results of endoscopic ultra-
Figure 2. Endoscopic ultrasonographic image of microlithiasis (arrows) within the gallbladder that was not detected by conventional percutaneous ultrasound. Microlithiasis is a hyperechoic signal without postacoustic shadow.
Figure 4. Endoscopic ultrasonographic image of pancreatic echogenic foci that represent calcifications (C) within the head of the pancreas. This finding is one of the main criteria for the diagnosis of chronic pancreatitis.
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Table 2. Results of the Multidisciplinary Investigations in Patients with “Idiopathic” Pancreatitis
Diagnosis
Endoscopic Cholangiography
Surgery
Medical Follow-Up and Bile Crystal Analysis
Total
Number (Percent) Biliary stones Chronic pancreatitis Pancreatic cancer Pancreatic intraductal mucin-producing tumor Ampulloma Choledocal cyst Other Idiopathic acute pancreatitis Total
87 (86) 1 (1) 2 (2)
8 (17) 16 (33)
4 (22) 1 (5)
3 (6) 3 (6) 1 (1) 10 (10) 101
4 (22) 10 (56) 18
19 (39) 49
sonography and the final diagnosis disagreed. Five of these patients, who had a normal endoscopic ultrasonographic examination and had been given a tentative diagnosis of idiopathic pancreatitis, had biliary stones demonstrated at surgery or bile crystal analysis. One patient who was diagnosed at endoscopic ultrasonography with a biliary stone had a choledocal cyst at the time of surgery, and 1 patient diagnosed with pancreatic cancer had focal chronic pancreatitis at surgery. Finally, endoscopic ultrasonography misdiagnosed 5 patients as having biliary stones and 1 patient as having pancreatic intraductal tumor in whom the final diagnosis was idiopathic pancreatitis (diagnosed by surgery [5 patients] or endoscopic cholangiopancreatography [1 patient]). When the results of endoscopic ultrasonography were compared with those of the additional studies, considered as the gold standard in our study, endoscopic ultrasound identified the correct cause of acute pancreatitis in 155 (92%) of the 168 patients, including 123 (95%) of the 130 patients in whom a definite cause of pancreatitis was established, and 32 (84%) of the 38 patients with a final diagnosis of idiopathic pancreatitis. In our study group, the cause of acute pancreatitis was determined in 130 (77%) patients; the remaining 38 (23%) patients were considered to have idiopathic pancreatitis.
DISCUSSION The diagnosis of idiopathic acute pancreatitis is timeconsuming, usually expensive, and may expose a patient to substantial morbidity from diagnostic tests (31). Endoscopic cholangiopancreatography, for example, is associated with a 5% to 6% morbidity rate (31–33) and may induce acute pancreatitis in patients with recurrent pancreatitis and undiagnosed dyskinesia of the sphincter of Oddi (34). Bile crystal analysis is difficult to perform, and
99 (59) 17 (10) 3 (2) 3 (2) 3 (2) 1 (1) 4 (2) 39 (22) 168
its usefulness depends on the location of bile collection (6 –10). Endoscopic ultrasonography can diagnose the cause of extrahepatic cholestasis (35) and is considered to be the endoscopic procedure of choice for visualizing the pancreas (14,16 –19). The positive predictive value of endoscopic ultrasonography for biliary tract disease is about 98% (15), and the procedure has few complications. In the present study, endoscopic ultrasonography correctly identified a cause of acute pancreatitis in 155 of the 168 patients in whom a cause was found by a multidisciplinary diagnostic approach, compared with only 19 of 38 patients in a previous study (27). Our findings support previous studies in which endoscopic ultrasonography was more sensitive and specific for detecting cholelithiasis than was conventional ultrasonography (36 –38). Understanding the cause of pancreatitis can modify a patient’s management and influence prognosis. When a biliary cause is identified and treated, the risk of recurrent pancreatitis is decreased. In recurrent pancreatitis without a known cause, prophylactic cholecystectomy—although sometimes performed— does not affect the recurrence rate (39). Indeed, in our study, 3 patients who underwent cholecystectomy had another attack of pancreatitis. In addition, endoscopic ultrasonography was able to diagnose pancreatic cancer, ampulloma, and intraductal mucin-producing tumors, which may manifest as acute pancreatitis. Thus, our results suggest that endoscopic ultrasonography is a valuable diagnostic tool for the management of patients with acute pancreatitis of unknown origin.
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