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Sphincter of Oddi dysfunction in children with recurrent pancreatitis and anomalous pancreaticobiliary union: an etiologic concept
Sphincter of Oddi dysfunction in children with recurrent pancreatitis and anomalous pancreaticobiliary union: an etiologic concept Moises Guelrud, MD, Claudio Morera, MD, Magaly Rodriguez, MD, Domingo Jaen, MD, Reinaldo Pierre, MD Caracas, Venezuela
Background: The exact cause of recurrent pancreatitis among patients with anomalous pancreaticobiliary union is not known. Sphincter of Oddi dysfunction has been implicated as a mechanism. This study evaluated sphincter of Oddi function in children with anomalous pancreaticobiliary union and recurrent pancreatitis and assessed the results of endoscopic sphincterotomy in the management of this condition. Methods: We retrospectively reviewed 128 endoscopic retrograde cholangiopancreatographic (ERCP) studies performed on children older than 1 year and adolescents with pancreaticobiliary disease. In 64 instances, ERCP was performed because of recurrent pancreatitis. Nine patients underwent sphincter of Oddi manometry followed by endoscopic sphincterotomy, and these patients were included in this study. A basal pressure greater than 35 mm Hg was considered diagnostic for sphincter of Oddi dysfunction. Follow-up data were obtained retrospectively from the patients’ relatives and referring physicians. Results: An anomalous pancreaticobiliary union was found in 18 of 64 (28%) patients with recurrent pancreatitis. The 9 patients who underwent sphincter manometry and endoscopic sphincterotomy were 5 girls and 4 boys 2.9 to 17 years of age (mean 7.8 years). A choledochal cyst was found in 7 of these 9 patients. Two patients had anomalous pancreaticobiliary union without common bile duct dilatation. All 9 patients had sphincter of Oddi dysfunction (mean basal pressure 96 ± 37.8 mm Hg, range 48 to 156 mm Hg). The length of the common channel was 22.8 ± 5.5 mm, and the length of the sphincter of Oddi segment was 12.1 ± 1.9 mm (p < 0.001). In all patients the sphincter of Oddi segment was located within the duodenal wall. The mean follow-up period after endoscopic sphincterotomy was 26.4 months (range 18 to 38 months). Eight patients had excellent results defined as absence of symptoms and no subsequent episodes of acute pancreatitis. Treatment of 1 patient was considered moderately successful because the patient still had occasional pain without pancreatic enzyme elevation but no subsequent episodes of acute pancreatitis. One patient had mild postprocedural pancreatitis. Conclusions: Recurrent pancreatitis and anomalous pancreaticobiliary union are associated with sphincter of Oddi dysfunction in children and adolescents. Endoscopic sphincterotomy is beneficial to these patients. (Gastrointest Endosc 1999;50:194-9.)
Anomalous pancreaticobiliary union (APBU) has been defined as communication of the common bile duct with the pancreatic duct to form a long common channel outside the duodenal wall and therefore not under the influence of the sphincter of Oddi. This anomaly has been implicated as a cause of choledochal cyst,1-3 bile duct and gallbladder carcinoma,4-7 and recurrent pancreatitis.8-14 Despite its observed association with and recurrent pancreatitis in children, there is only limited Received June 12, 1998. For revision October 1, 1998. Accepted December 18, 1998. From the Gastroenterology Department and Pediatric Gastroenterology Unit, Hospital General del Oeste, Caracas, Venezuela. Reprint requests: Moises Guelrud, MD, Policlínica Metropolitana, Urb. Caurimare, Calle A1, Caracas 1060, Venezuela. Copyright © 1999 by the American Society for Gastrointestinal Endoscopy 0016-5107/99/$8.00 + 0 37/1/97207 194
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understanding of the role of APBU in the pathogenesis of recurrent pancreatitis. It has been postulated that temporary occlusion of pancreatic secretion by a stone, protein plugs, or sphincter of Oddi dysfunction may be responsible for the recurrent attacks.10 However, little information has been reported concerning possible sphincter of Oddi dysfunction in these patients. Some studies have documented elevated sphincter of Oddi basal pressures,15,16 whereas others have found that pressures are similar in patients with APBU and control subjects.17,18 The purpose of this study was to determine whether there is an association between sphincter of Oddi dysfunction and recurrent pancreatitis in patients with APBU. PATIENTS AND METHODS We retrospectively reviewed 128 ERCP studies performed between January 1983 and January 1997 on chilVOLUME 50, NO. 2, 1999
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dren older than 1 year and adolescents with pancreaticobiliary disease. An APBU was found in 42 of 64 (65%) patients with biliary diseases and 18 of 64 (28%) patients with pancreatic disease. Sphincter of Oddi manometry was performed on 9 of these children with recurrent pancreatitis, and these patients were included in this study. The criteria for patient selection were more than two episodes of acute pancreatitis, one episode of acute pancreatitis with choledochal cyst found at abdominal US or CT, and presence of APBU at ERCP. None of these patients had hereditary pancreatitis, cystic fibrosis, hyperlipidemia, history of trauma, use of medication associated with pancreatitis, or hypercalcemia. Endoscopic manipulations were performed at least 1 month after the last attack of acute pancreatitis. ERCP was performed before sphincter of Oddi manometry on a separate day in a standard manner with the same duodenoscope used for examinations of adults (JF-1T20 or JF-130; Olympus America, Inc., Melville, N.Y.). Choledochal cysts were classified according to Todani et al.19 into the following five types: type IA, classic fusiform cyst; type IB, segmental choledochal dilatation; type IC, diffuse or cylindrical dilatation; type II, diverticulum arising in the extrahepatic duct; type III, choledochocele; type IVA, multiple cysts of the extrahepatic bile ducts with intrahepatic cysts; type IVB, without intrahepatic cysts; and type V, Caroli’s disease. None of the patients with choledochal cyst had the cyst removed before our evaluation. To obtain good visualization of the common channel the main duodenal papilla was cannulated just at its tip. Four to six radiographs for each patient were available for evaluation. To account for magnification, the distal end of the duodenoscope was measured and the length of the common channel was adjusted accordingly. An APBU was defined as a long common channel located outside the duodenal wall. The length of the common channel was considered abnormal if it measured more than 4.5 mm in children younger than 12 years,20 and if it was longer than 5 mm in older children and adolescents.21 The APBU was classified according to Kimura et al.4 as biliary type (BP) when the common bile duct joined the pancreatic duct and pancreatic type (PB) when the pancreatic duct joined the common duct. We added a third type, long Y, when there was only a long common channel without a choledochal cyst (Fig. 1).20 Pancreatic ductograms were graded according to the Cambridge classification of chronic pancreatitis22 as normal (quality study depicting the entire gland without abnormal features), equivocal (normal main pancreatic duct with fewer than 3 abnormal side branches), mild (normal main with 3 or more abnormal side branches), moderate (abnormal main duct with more than 3 abnormal pancreatic branches), and severe (moderate changes with one or more of large cavity, obstruction, filling defects, severe dilatation, or irregularity). Sphincter of Oddi manometry was performed on all patients after an overnight fast and conscious sedation with diazepam (0.1 to 0.3 mg/kg, maximum 15 mg) or midazolam (0.1 to 0.3 mg/kg, maximum 15 mg). A standard duodenoscope of the type used for examinations of VOLUME 50, NO. 2, 1999
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Figure 1. Schematic of anomalous pancreaticobiliary union. A, BP type. The common bile duct appears to join the pancreatic duct. B, PB type. The pancreatic duct appears to join the common bile duct. C, Long Y type. There is only a long common channel. Reprinted with permission from Isis Medical Media (Guelrud et al.20) adults (JF-1T20, Olympus) was used. Pressures were recorded with a low-compliance infusion pump system (Arndorfer Medical Specialties, Greendale, Wis.), and a 5F triple-lumen aspiration catheter (Wilson-Cook Medical, Winston-Salem, N.C.) with the middle port used for aspiration.23 Because of the difficulties involved in performing sphincter of Oddi manometry on healthy children, values obtained for adults were taking as normal. Basal sphincter pressure was considered abnormal if the mean of the highest single pressure in each of two pull-throughs was greater than 35 mm Hg.24 Phasic wave amplitude, frequency, and duration were not assessed. After pressure measurements, the catheter was slowly withdrawn to measure the length of the sphincter segment. Sphincterotomy of the common channel was performed on 4 patients with a standard traction sphincterotome with a 20 mm cutting wire. A stepwise cut was made in the 11 to 12 o’clock position and extended cephalad through 85% to 95% of the length of the longitudinal fold. In 5 patients a 5F pancreatic stent was placed across the major papilla after sphincterotomy to reduce risk for postprocedural pancreatitis.25 Stents were removed 7 to 10 days after insertion. Patients were observed for postprocedural complications. Pancreatitis resulting from the endoscopic therapy was graded as follows: (1) mild (hospitalization was required for 2 to 3 days after the procedure); (2) moderate (hospitalization extended for 4 to 10 days after the procedure); and (3) severe (hospitalization for more than 10 days; development of hemorrhagic pancreatitis, pseudocyst, or phlegmon; or intervention needed).26 Follow-up data were obtained retrospectively from the patients’ relatives and referring physicians. The number of episodes of pancreatitis, epigastric pain, pancreatic enzyme evaluation, and emergency visits after treatment were determined and compared with the number before treatment. Improvement was graded at follow-up evaluation in the following manner: (1) none (recurrent pancreatitis requiring emergency visits and hospitalization); (2) moderate (occasional pain without pancreatic enzyme elevation and no subsequent episodes of acute pancreatitis); GASTROINTESTINAL ENDOSCOPY
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Figure 2. Anomalous pancreaticobiliary union of BP type.
Figure 4. Anomalous pancreaticobiliary union of long Y type.
Figure 3. Anomalous pancreaticobiliary union of PB type. Reprinted with permission from Guelrud et al.20 3) excellent (absence of symptoms and no subsequent episodes of acute pancreatitis). The results are expressed as mean ± SD (range). Significance of differences between mean values was analyzed with Student’s t test for paired data.
RESULTS The clinical characteristics of the 9 patients with APBU are summarized in Table 1. There were 5 girls and 4 boys 2.9 to 17 years of age (mean 7.8 years). Seven patients had choledochal cyst (4 IC and 3 IVA). Three patients had BP type APBU (Fig. 2), 4 196
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patients had PB type (Fig. 3), and 2 patients long Y type (Fig. 4). Six patients had normal pancreatographic findings, and 3 patients had moderate pancreatic duct changes of chronic pancreatitis. The length of the anomalous common channel was 22.8 ± 5.5 mm (range 16 to 33 mm) and the length of the sphincter of Oddi segment was 12.1 ± 1.9 mm (range 9 to 15 mm) (p < 0.001). Thus the sphincter of Oddi was located only at the distal portion of the APBU within the duodenal wall. All 9 patients had elevated basal sphincter of Oddi pressure with a mean of 96.2 ± 37.8 mm Hg (range 48 to 156 mm Hg). There was no difference in basal sphincter of Oddi pressure among the different types of APBU. All 9 patients underwent endoscopic sphincterotomy. One episode of mild postprocedural pancreatitis occurred among 1 of 4 patients who underwent standard endoscopic sphincterotomy. This patient had a normal pancreatogram and was treated conservatively. There were no complications among the 5 patients treated by sphincterotomy followed by means of pancreatic stent placement. Eight patients had excellent and 1 patient had moderate results over a mean follow-up period of 26.4 months (range 18 to 38 months). DISCUSSION APBU is an unusual finding among patients with biliopancreatic disorders. Babbitt et al.1 proposed that the presence of this anomaly might be related VOLUME 50, NO. 2, 1999
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Table 1. Characteristics of the 9 patients with APBU Patient No. 1 2 3 4 5 6 7 8 9
Gender M F M F M M F F F
Age (yr) 8 5 2.9 5 3 12 6 12 17
Type of choledochal cyst IC IC IC IC IVA IVA IVA — —
Type of APBU
Length of APBU (mm)
PB BP PB PB BP BP PB Long Y Long Y
33 24 16 25 17 18 21 24 28
Length of sphincter of Oddi (mm) 14 12 11 13 9 12 10 15 13
Pancreatic ductography changes Moderate Moderate None None None Moderate None None None
Basal sphincter of Oddi pressure (mm Hg) 80 60 156 120 90 48 76 150 86
APBU, Anomalous pancreaticobiliary union; PB, pancreaticobiliary; BP, biliopancreatic.
to the development of choledochal cyst. However, it is not always associated with choledochal cyst.13 According to Babbitt’s hypothesis, regurgitation of pancreatic secretions into the biliary tract may damage the bile duct and cause abnormal dilatation. APBU has been implicated as a cause of recurrent pancreatitis.8-14 Babbitt’s theory, however, does not explain the association between APBU and recurrent pancreatitis. Raffensperger et al.9 postulated that bile reflux into the pancreatic duct is the most likely cause of pancreatitis. Mori et al.10 suggested that bile reflux occurs when the common channel is obstructed temporarily; they speculate that this could be caused by sphincter of Oddi dysfunction. It is difficult to accept the theory of bile reflux into the pancreatic duct, because the excretory pressure of the pancreas exceeds that of the biliary system. Pancreatic duct pressure has been shown to be higher than common duct pressure in control subjects20 and in patients with various pancreaticobiliary disorders and normally arranged ductal systems.27 A positive pressure gradient from the pancreatic duct to the common duct in a patient with APBU and choledochal cyst has been reported.28 As evidence of the higher excretory pressure of the pancreas, influx of pancreatic juice into the biliary tract with high amylase levels has been found in the gallbladder and choledochal cyst aspirates.1,29 Sphincter of Oddi motility has been scarcely studied among patients with APBU. Ochi et al.17 demonstrated similar basal sphincter of Oddi pressures between patients with APBU and control subjects. Take et al.16 found elevated basal sphincter of Oddi pressures in 9 patients with choledochal cyst and APBU. Matsumoto et al.18 performed sphincter of Oddi manometry on 7 patients with APBU, 4 with choledochal cyst, and control subjects. They found similar basal sphincter of Oddi pressures in both groups. However, none of their patients had recurrent pancreatitis, which may account for the disVOLUME 50, NO. 2, 1999
crepancy between the results of their study and those of previous studies. In our study, an association was demonstrated between sphincter of Oddi dysfunction and recurrent pancreatitis among patients with APBU. In particular, sphincter of Oddi dysfunction, as characterized by an abnormally high basal pressure, was found. It is possible that transient and intermittent elevation in intraductal pressure within the pancreatic duct may be responsible for acute attacks of pancreatitis among patients with APBU. The length of the segment with contractile activity in patients with APBU appears to be similar to that of the healthy population. Kimura et al.5 measured the length of the common channel and the length of the segment with contractile activity on serial cholangiograms of patients with APBU and of control subjects. Patients with APBU had a longer common channel than the control subjects, but the length of the segment with contractile activity was similar in both groups. Matsumoto et al.18 performed sphincter of Oddi manometry on patients with APBU and a control group. They showed that the length of the sphincter of Oddi segment with phasic wave activity was similar in both groups. Similar conclusions have been reached in autopsy studies.30 We corroborated these findings in our study. The mean (± SD) length of the common channel among our 9 patients was 22.8 ± 5.5 mm, which was significantly greater than the mean length of the sphincter of Oddi segment (12.1 ± 1.9 mm). The normal length of the sphincter of Oddi segment and its location within the duodenal wall have important implications for therapy. Elevated sphincter of Oddi pressure in a child with APBU and a choledochal cyst should prompt further consideration of a drainage procedure to preserve essential pancreatic endocrine function. Surgical sphincteroplasty11 and surgical excision of the APBU with hepaticojejunosotomy10 have been used successfully GASTROINTESTINAL ENDOSCOPY
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in the management of APBU. Although transient improvement has been found with balloon dilatation of the common channel,31 endoscopic therapy has scarcely been used in the belief that the length of the muscle segment of the sphincter of Oddi extended beyond the duodenal wall and thus precluded endoscopic sphincterotomy. However, because patients with APBU have a sphincter of Oddi muscular segment that is normal in length and location in the duodenal wall, endoscopic therapy may be indicated. Total division of the sphincter by means of endoscopic sphincterotomy may offer a high probability of cure. Our results support this hypothesis. Ng et al.32 reported clinical improvement for 5 of 6 patients with APBU. Samavedy et al.33 performed endoscopic sphincterotomy of the common channel on 12 adult patients with recurrent pancreatitis and APBU. After endoscopic therapy 7 patients had no further pancreatitis, and 5 patients continued to have pancreatitis. Pancreatitis as a complication of therapy occurred in 1 of 9 patients but was mild and managed conservatively. Anatomic alterations of the pancreatic duct after pancreatic duct stent placement have been reported.34,35 Despite the tendency for these ductal changes to improve with time after stent removal, the long-term consequences of these stent-induced changes are unknown. We limit our duration of stenting to 7 to 10 days in an attempt to minimize the severity of ductal changes. Little information has been reported concerning the pancreatic ducts of patients with APBU. Some studies have documented abnormal pancreatographic findings,10,13,14,33 whereas others have found the pancreatic duct to be normal.36,37 In our study, 3 of 7 patients with choledochal cyst and sphincter of Oddi dysfunction had chronic pancreatitis; these patients were older (mean age 8.3 years) than those without chronic pancreatitis (mean age 4.2 years). Perhaps pancreatic duct changes become more severe through the years, as has been shown among adult patients with unexplained abdominal pain with chronic pancreatitis and sphincter of Oddi dysfunction38 and adult patients with recurrent pancreatitis and APBU.33 This study indicated that recurrent pancreatitis and APBU are associated with sphincter of Oddi dysfunction among children and adolescents. In these patients the sphincter of Oddi muscular segment is located within the duodenal wall. The results for this series indicate that endoscopic sphincterotomy is reasonably effective treatment of these patients. It is proposed that the mechanism for recurrent pancreatitis among patients with APBU is abnormal function of the sphincter of Oddi. 198
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This theory is supported by the excellent clinical response after endoscopic sphincterotomy found in this study. REFERENCES 1. Babbitt DP, Starshak RJ, Clemett AR. Choledochal cyst: a concept of etiology. AJR 1973;119:57-62. 2. Arima E, Akita H. Congenital biliary tract dilatation and anomalous junction of the pancreaticobiliary system. J Pediatr Surg 1979;14:9-15. 3. Guelrud M, Jaen D, Mendoza S, Torres P. Usefulness of endoscopic retrograde cholangiopancreatography in diagnosis of choledochal cysts in children. GEN 1989;43:9-12. 4. Suda K, Miyano T, Konuma I, Matsumoto M. An abnormal pancreatico-choledocho ductal junction in cases of biliary tract carcinoma. Cancer 1983;52:2086-8. 5. Kimura K, Ohto M, Saisho H, Unozawa T, Tsuchiya Y, Morita M, et al. Association of gallbladder carcinoma and anomalous pancreaticobiliary ductal union. Gastroenterology 1985;89: 1258-65. 6. Misra SP, Gulati P, Thorat VK, Vij JC, Anand BS. Pancreaticobiliary ductal union in biliary diseases: an endoscopic retrograde cholangiopancreatography study. Gastroenterology 1989;96:907-12. 7. Todani T, Watanabe Y, Fujii T, Ukemura S. Anomalous arrangement of the pancreaticobiliary ductal system in patients with a choledochal cyst. Am J Surg 1984;147:672-6. 8. Gibson LE, Haller JA. Acute pancreatitis associated with congenital cyst of the common bile duct. J Pediatr 1959;55:650-7. 9. Raffensperger BG, Given GZ, Warner RA. Fusiform dilatation of the common bile duct with pancreatitis. J Pediatr Surg 1973;8:907-10. 10. Mori K, Nagakawa T, Ohta T, Nakano T, Kadoya N, Kayahara M, et al. Acute pancreatitis associated with anomalous union of the pancreaticobiliary ductal system. J Clin Gastroenterol 1991;13:673-7. 11. Karp MP, Jewett TC, Cooney DR. Chronic relapsing pancreatitis in childhood caused by pancreaticobiliary ductal anomaly. J Pediatr Gastroenterol Nutr 1983;2:324-8. 12. Mohan P, Holcomb GW, Ziegler MM. Recurrent jaundice and pancreatitis in a child with pancreatobiliary duct anomalies. J Pediatr Gastroenterol Nutr 1994;18:386-90. 13. Kato O, Hattori K, Suzuki T, Tachino F, Yuasa T. Clinical significance of anomalous pancreaticobiliary union. Gastrointest Endosc 1983;29:94-8. 14. Guelrud M, Mujica C, Jaen D, Plaz J, Arias J. The role of ERCP in the diagnosis and treatment of idiopathic recurrent pancreatitis in children and adolescents. Gastrointest Endosc 1994;40:428-36. 15. Ponce J, Garrigues V, Sala T, Pertejo V, Berenguer J. Endoscopic biliary manometry in patients with suspected sphincter of Oddi dysfunction and in patients with cystic dilatation of the bile ducts. Dig Dis Sci 1989;34:367-71. 16. Take S, Okabe I, Morita K. Endoscopic manometric study of sphincter of Oddi for congenital bile duct dilatation [abstract in English]. Jpn J Pediatr Surg 1988;20:303-9. 17. Ochi T, Nakazawa S, Naito Y. Endoscopic manometry of the sphincter of Oddi and pancreatic duct in patients with anomalous arrangement of the pancreaticobiliary ductal system [Japanese]. J Jpn Soc Biliopancreatic Physiol 1989;5:27-35. 18. Matsumoto S, Tanaka M, Ikeda S, Yoshimoto H. Sphincter of Oddi motor activity in patients with anomalous pancreaticobiliary junction. Am J Gastroenterol 1991;86:831-4. 19. Todani T, Watanabe Y, Narusue M. Congenital bile duct cyst. Am J Surg 1977;134:263-9.
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20. Guelrud MG, Carr-Locke DL, Fox V. ERCP in pediatric practice: diagnosis and treatment. Oxford, UK: Isis Medical Media; 1997. 21. Guelrud M, Morera C, Rodriguez M, Prados JG, Jaen D. Normal and anomalous pancreaticobiliary union in children and adolescents. Gastrointest Endosc 1999;50:189-93. 22. Axon ATR, Classen M, Cotton PB, Cremer M, Freeny PC, Lees WR. Pancreatography in chronic pancreatitis: international definitions. Gut 1984;25:1107-12. 23. Sherman S, Troiano FP, Hawes RH, Lehman G. Sphincter of Oddi manometry: decreased risk of clinical pancreatitis with use of a modified aspirating catheter. Gastrointest Endosc 1990;36:462-6. 24. Guelrud M, Mendoza S, Rossiter G, Villegas MI. Sphincter of Oddi manometry in healthy volunteers. Dig Dis Sci 1990;35: 38-46. 25. Lehman GA, Sherman S, Nisi R, Hawes RH. Pancreas divisum: results of minor papilla sphincterotomy. Gastrointest Endosc 1993;39:1-8. 26. Cotton PB, Lehman GA, Vennes J, Geenen JE, Rusell RC, Meyers WC, et al. Endoscopic sphincterotomy complications and their management: an attempt at consensus. Gastrointest Endosc 1991;37:383-93. 27. Guelrud M, Mendoza S, Vicent S, Gomez M, Villalta B. Pressures in the sphincter of Oddi in patients with gallstones, common duct stones, and recurrent pancreatitis. J Clin Gastroenterol 1983;5:37-41. 28. Tanaka M, Ikeda S, Kawakami K, Nakayama F. The presence of a positive pressure gradient from pancreatic duct to choledochal cyst demonstrated by duodenoscopic microtransducer manometry: clue to pancreaticobiliary reflux. Endoscopy 1982;14:45-7. 29. Kinoshita H, Nagata E, Hirohashi K, Sakai K, Kobayashi Y. Carcinoma of the gallbladder with an anomalous connection between the choledochus and the pancreatic duct. Cancer 1984;54:762-9.
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30. Miyano T, Suruga K, Suda K. Abnormal choledocho-pancreatico ductal junction related to the etiology of infantile obstructive jaundice diseases. J Pediatr Surg 1979;14:16-26. 31. Sebesta C, Schmid A, Kier P, Ruckser R, Tiefengraber E, Rosen H, et al. ERCP and balloon dilatation is a valuable alternative to surgical biliodigestive anastomosis in the long common channel syndrome in childhood. Endoscopy 1995; 27:709-10. 32. Ng WD, Liu K, Wong MK, Long CK, Lee K, Chan YT, et al. Endoscopic sphincterotomy in young patients with choledochal dilation and a long common channel: a preliminary report. Br J Surg 1992;79:550-2. 33. Samavedy R, Sherman S, Lehman G. Endoscopic diagnosis and therapy of anomalous pancreatico-biliary junction [abstract]. Gastrointest Endosc 1997;45:AB164. 34. Kozarek RA. Pancreatic stents can induce ductal changes consistent with chronic pancreatitis. Gastrointest Endosc 1990;36:93-5. 35. Sherman S, Alvarez C, Robert M, Ashley SW, Reber HA, Lehman GA. Polyethylene pancreatic duct stent-induced changes in the normal dog pancreas. Gastrointest Endosc 1993;39:658-64. 36. Kimura K. Studies in 28 cases of congenital cystic dilatation of the common bile duct in adults: roentgenological features and union between the choledochus and the main pancreatic duct [abstract in English]. Jpn J Gastroenterol 1976;73: 401-14. 37. Sano H, Nakazawa S, Naito Y. Radiological study of the abnormal pancreaticocholangio-connection, with special reference to the “congenital choledochal cyst.” Gastroenterol Endosc 1981;23:1722-35. 38. Tarnasky PR, Hoffman B, Aabakken L, Knapple WL, Coyle W, Pineau B, et al. Sphincter of Oddi dysfunction is associated with chronic pancreatitis. Am J Gastroenterol 1997;92: 1125-9.
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Background: The exact cause of recurrent pancreatitis among patients with anomalous pancreaticobiliary union is not known. Sphincter of Oddi dysfunction has been implicated as a mechanism. This study evaluated sphincter of Oddi function in children with anomalous pancreaticobiliary union and recurrent pancreatitis and assessed the results of endoscopic sphincterotomy in the management of this condition. Methods: We retrospectively reviewed 128 endoscopic retrograde cholangiopancreatographic (ERCP) studies performed on children older than 1 year and adolescents with pancreaticobiliary disease. In 64 instances, ERCP was performed because of recurrent pancreatitis. Nine patients underwent sphincter of Oddi manometry followed by endoscopic sphincterotomy, and these patients were included in this study. A basal pressure greater than 35 mm Hg was considered diagnostic for sphincter of Oddi dysfunction. Follow-up data were obtained retrospectively from the patients’ relatives and referring physicians. Results: An anomalous pancreaticobiliary union was found in 18 of 64 (28%) patients with recurrent pancreatitis. The 9 patients who underwent sphincter manometry and endoscopic sphincterotomy were 5 girls and 4 boys 2.9 to 17 years of age (mean 7.8 years). A choledochal cyst was found in 7 of these 9 patients. Two patients had anomalous pancreaticobiliary union without common bile duct dilatation. All 9 patients had sphincter of Oddi dysfunction (mean basal pressure 96 ± 37.8 mm Hg, range 48 to 156 mm Hg). The length of the common channel was 22.8 ± 5.5 mm, and the length of the sphincter of Oddi segment was 12.1 ± 1.9 mm (p < 0.001). In all patients the sphincter of Oddi segment was located within the duodenal wall. The mean follow-up period after endoscopic sphincterotomy was 26.4 months (range 18 to 38 months). Eight patients had excellent results defined as absence of symptoms and no subsequent episodes of acute pancreatitis. Treatment of 1 patient was considered moderately successful because the patient still had occasional pain without pancreatic enzyme elevation but no subsequent episodes of acute pancreatitis. One patient had mild postprocedural pancreatitis. Conclusions: Recurrent pancreatitis and anomalous pancreaticobiliary union are associated with sphincter of Oddi dysfunction in children and adolescents. Endoscopic sphincterotomy is beneficial to these patients. (Gastrointest Endosc 1999;50:194-9.)
Anomalous pancreaticobiliary union (APBU) has been defined as communication of the common bile duct with the pancreatic duct to form a long common channel outside the duodenal wall and therefore not under the influence of the sphincter of Oddi. This anomaly has been implicated as a cause of choledochal cyst,1-3 bile duct and gallbladder carcinoma,4-7 and recurrent pancreatitis.8-14 Despite its observed association with and recurrent pancreatitis in children, there is only limited Received June 12, 1998. For revision October 1, 1998. Accepted December 18, 1998. From the Gastroenterology Department and Pediatric Gastroenterology Unit, Hospital General del Oeste, Caracas, Venezuela. Reprint requests: Moises Guelrud, MD, Policlínica Metropolitana, Urb. Caurimare, Calle A1, Caracas 1060, Venezuela. Copyright © 1999 by the American Society for Gastrointestinal Endoscopy 0016-5107/99/$8.00 + 0 37/1/97207 194
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understanding of the role of APBU in the pathogenesis of recurrent pancreatitis. It has been postulated that temporary occlusion of pancreatic secretion by a stone, protein plugs, or sphincter of Oddi dysfunction may be responsible for the recurrent attacks.10 However, little information has been reported concerning possible sphincter of Oddi dysfunction in these patients. Some studies have documented elevated sphincter of Oddi basal pressures,15,16 whereas others have found that pressures are similar in patients with APBU and control subjects.17,18 The purpose of this study was to determine whether there is an association between sphincter of Oddi dysfunction and recurrent pancreatitis in patients with APBU. PATIENTS AND METHODS We retrospectively reviewed 128 ERCP studies performed between January 1983 and January 1997 on chilVOLUME 50, NO. 2, 1999
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dren older than 1 year and adolescents with pancreaticobiliary disease. An APBU was found in 42 of 64 (65%) patients with biliary diseases and 18 of 64 (28%) patients with pancreatic disease. Sphincter of Oddi manometry was performed on 9 of these children with recurrent pancreatitis, and these patients were included in this study. The criteria for patient selection were more than two episodes of acute pancreatitis, one episode of acute pancreatitis with choledochal cyst found at abdominal US or CT, and presence of APBU at ERCP. None of these patients had hereditary pancreatitis, cystic fibrosis, hyperlipidemia, history of trauma, use of medication associated with pancreatitis, or hypercalcemia. Endoscopic manipulations were performed at least 1 month after the last attack of acute pancreatitis. ERCP was performed before sphincter of Oddi manometry on a separate day in a standard manner with the same duodenoscope used for examinations of adults (JF-1T20 or JF-130; Olympus America, Inc., Melville, N.Y.). Choledochal cysts were classified according to Todani et al.19 into the following five types: type IA, classic fusiform cyst; type IB, segmental choledochal dilatation; type IC, diffuse or cylindrical dilatation; type II, diverticulum arising in the extrahepatic duct; type III, choledochocele; type IVA, multiple cysts of the extrahepatic bile ducts with intrahepatic cysts; type IVB, without intrahepatic cysts; and type V, Caroli’s disease. None of the patients with choledochal cyst had the cyst removed before our evaluation. To obtain good visualization of the common channel the main duodenal papilla was cannulated just at its tip. Four to six radiographs for each patient were available for evaluation. To account for magnification, the distal end of the duodenoscope was measured and the length of the common channel was adjusted accordingly. An APBU was defined as a long common channel located outside the duodenal wall. The length of the common channel was considered abnormal if it measured more than 4.5 mm in children younger than 12 years,20 and if it was longer than 5 mm in older children and adolescents.21 The APBU was classified according to Kimura et al.4 as biliary type (BP) when the common bile duct joined the pancreatic duct and pancreatic type (PB) when the pancreatic duct joined the common duct. We added a third type, long Y, when there was only a long common channel without a choledochal cyst (Fig. 1).20 Pancreatic ductograms were graded according to the Cambridge classification of chronic pancreatitis22 as normal (quality study depicting the entire gland without abnormal features), equivocal (normal main pancreatic duct with fewer than 3 abnormal side branches), mild (normal main with 3 or more abnormal side branches), moderate (abnormal main duct with more than 3 abnormal pancreatic branches), and severe (moderate changes with one or more of large cavity, obstruction, filling defects, severe dilatation, or irregularity). Sphincter of Oddi manometry was performed on all patients after an overnight fast and conscious sedation with diazepam (0.1 to 0.3 mg/kg, maximum 15 mg) or midazolam (0.1 to 0.3 mg/kg, maximum 15 mg). A standard duodenoscope of the type used for examinations of VOLUME 50, NO. 2, 1999
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Figure 1. Schematic of anomalous pancreaticobiliary union. A, BP type. The common bile duct appears to join the pancreatic duct. B, PB type. The pancreatic duct appears to join the common bile duct. C, Long Y type. There is only a long common channel. Reprinted with permission from Isis Medical Media (Guelrud et al.20) adults (JF-1T20, Olympus) was used. Pressures were recorded with a low-compliance infusion pump system (Arndorfer Medical Specialties, Greendale, Wis.), and a 5F triple-lumen aspiration catheter (Wilson-Cook Medical, Winston-Salem, N.C.) with the middle port used for aspiration.23 Because of the difficulties involved in performing sphincter of Oddi manometry on healthy children, values obtained for adults were taking as normal. Basal sphincter pressure was considered abnormal if the mean of the highest single pressure in each of two pull-throughs was greater than 35 mm Hg.24 Phasic wave amplitude, frequency, and duration were not assessed. After pressure measurements, the catheter was slowly withdrawn to measure the length of the sphincter segment. Sphincterotomy of the common channel was performed on 4 patients with a standard traction sphincterotome with a 20 mm cutting wire. A stepwise cut was made in the 11 to 12 o’clock position and extended cephalad through 85% to 95% of the length of the longitudinal fold. In 5 patients a 5F pancreatic stent was placed across the major papilla after sphincterotomy to reduce risk for postprocedural pancreatitis.25 Stents were removed 7 to 10 days after insertion. Patients were observed for postprocedural complications. Pancreatitis resulting from the endoscopic therapy was graded as follows: (1) mild (hospitalization was required for 2 to 3 days after the procedure); (2) moderate (hospitalization extended for 4 to 10 days after the procedure); and (3) severe (hospitalization for more than 10 days; development of hemorrhagic pancreatitis, pseudocyst, or phlegmon; or intervention needed).26 Follow-up data were obtained retrospectively from the patients’ relatives and referring physicians. The number of episodes of pancreatitis, epigastric pain, pancreatic enzyme evaluation, and emergency visits after treatment were determined and compared with the number before treatment. Improvement was graded at follow-up evaluation in the following manner: (1) none (recurrent pancreatitis requiring emergency visits and hospitalization); (2) moderate (occasional pain without pancreatic enzyme elevation and no subsequent episodes of acute pancreatitis); GASTROINTESTINAL ENDOSCOPY
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Figure 2. Anomalous pancreaticobiliary union of BP type.
Figure 4. Anomalous pancreaticobiliary union of long Y type.
Figure 3. Anomalous pancreaticobiliary union of PB type. Reprinted with permission from Guelrud et al.20 3) excellent (absence of symptoms and no subsequent episodes of acute pancreatitis). The results are expressed as mean ± SD (range). Significance of differences between mean values was analyzed with Student’s t test for paired data.
RESULTS The clinical characteristics of the 9 patients with APBU are summarized in Table 1. There were 5 girls and 4 boys 2.9 to 17 years of age (mean 7.8 years). Seven patients had choledochal cyst (4 IC and 3 IVA). Three patients had BP type APBU (Fig. 2), 4 196
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patients had PB type (Fig. 3), and 2 patients long Y type (Fig. 4). Six patients had normal pancreatographic findings, and 3 patients had moderate pancreatic duct changes of chronic pancreatitis. The length of the anomalous common channel was 22.8 ± 5.5 mm (range 16 to 33 mm) and the length of the sphincter of Oddi segment was 12.1 ± 1.9 mm (range 9 to 15 mm) (p < 0.001). Thus the sphincter of Oddi was located only at the distal portion of the APBU within the duodenal wall. All 9 patients had elevated basal sphincter of Oddi pressure with a mean of 96.2 ± 37.8 mm Hg (range 48 to 156 mm Hg). There was no difference in basal sphincter of Oddi pressure among the different types of APBU. All 9 patients underwent endoscopic sphincterotomy. One episode of mild postprocedural pancreatitis occurred among 1 of 4 patients who underwent standard endoscopic sphincterotomy. This patient had a normal pancreatogram and was treated conservatively. There were no complications among the 5 patients treated by sphincterotomy followed by means of pancreatic stent placement. Eight patients had excellent and 1 patient had moderate results over a mean follow-up period of 26.4 months (range 18 to 38 months). DISCUSSION APBU is an unusual finding among patients with biliopancreatic disorders. Babbitt et al.1 proposed that the presence of this anomaly might be related VOLUME 50, NO. 2, 1999
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Table 1. Characteristics of the 9 patients with APBU Patient No. 1 2 3 4 5 6 7 8 9
Gender M F M F M M F F F
Age (yr) 8 5 2.9 5 3 12 6 12 17
Type of choledochal cyst IC IC IC IC IVA IVA IVA — —
Type of APBU
Length of APBU (mm)
PB BP PB PB BP BP PB Long Y Long Y
33 24 16 25 17 18 21 24 28
Length of sphincter of Oddi (mm) 14 12 11 13 9 12 10 15 13
Pancreatic ductography changes Moderate Moderate None None None Moderate None None None
Basal sphincter of Oddi pressure (mm Hg) 80 60 156 120 90 48 76 150 86
APBU, Anomalous pancreaticobiliary union; PB, pancreaticobiliary; BP, biliopancreatic.
to the development of choledochal cyst. However, it is not always associated with choledochal cyst.13 According to Babbitt’s hypothesis, regurgitation of pancreatic secretions into the biliary tract may damage the bile duct and cause abnormal dilatation. APBU has been implicated as a cause of recurrent pancreatitis.8-14 Babbitt’s theory, however, does not explain the association between APBU and recurrent pancreatitis. Raffensperger et al.9 postulated that bile reflux into the pancreatic duct is the most likely cause of pancreatitis. Mori et al.10 suggested that bile reflux occurs when the common channel is obstructed temporarily; they speculate that this could be caused by sphincter of Oddi dysfunction. It is difficult to accept the theory of bile reflux into the pancreatic duct, because the excretory pressure of the pancreas exceeds that of the biliary system. Pancreatic duct pressure has been shown to be higher than common duct pressure in control subjects20 and in patients with various pancreaticobiliary disorders and normally arranged ductal systems.27 A positive pressure gradient from the pancreatic duct to the common duct in a patient with APBU and choledochal cyst has been reported.28 As evidence of the higher excretory pressure of the pancreas, influx of pancreatic juice into the biliary tract with high amylase levels has been found in the gallbladder and choledochal cyst aspirates.1,29 Sphincter of Oddi motility has been scarcely studied among patients with APBU. Ochi et al.17 demonstrated similar basal sphincter of Oddi pressures between patients with APBU and control subjects. Take et al.16 found elevated basal sphincter of Oddi pressures in 9 patients with choledochal cyst and APBU. Matsumoto et al.18 performed sphincter of Oddi manometry on 7 patients with APBU, 4 with choledochal cyst, and control subjects. They found similar basal sphincter of Oddi pressures in both groups. However, none of their patients had recurrent pancreatitis, which may account for the disVOLUME 50, NO. 2, 1999
crepancy between the results of their study and those of previous studies. In our study, an association was demonstrated between sphincter of Oddi dysfunction and recurrent pancreatitis among patients with APBU. In particular, sphincter of Oddi dysfunction, as characterized by an abnormally high basal pressure, was found. It is possible that transient and intermittent elevation in intraductal pressure within the pancreatic duct may be responsible for acute attacks of pancreatitis among patients with APBU. The length of the segment with contractile activity in patients with APBU appears to be similar to that of the healthy population. Kimura et al.5 measured the length of the common channel and the length of the segment with contractile activity on serial cholangiograms of patients with APBU and of control subjects. Patients with APBU had a longer common channel than the control subjects, but the length of the segment with contractile activity was similar in both groups. Matsumoto et al.18 performed sphincter of Oddi manometry on patients with APBU and a control group. They showed that the length of the sphincter of Oddi segment with phasic wave activity was similar in both groups. Similar conclusions have been reached in autopsy studies.30 We corroborated these findings in our study. The mean (± SD) length of the common channel among our 9 patients was 22.8 ± 5.5 mm, which was significantly greater than the mean length of the sphincter of Oddi segment (12.1 ± 1.9 mm). The normal length of the sphincter of Oddi segment and its location within the duodenal wall have important implications for therapy. Elevated sphincter of Oddi pressure in a child with APBU and a choledochal cyst should prompt further consideration of a drainage procedure to preserve essential pancreatic endocrine function. Surgical sphincteroplasty11 and surgical excision of the APBU with hepaticojejunosotomy10 have been used successfully GASTROINTESTINAL ENDOSCOPY
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in the management of APBU. Although transient improvement has been found with balloon dilatation of the common channel,31 endoscopic therapy has scarcely been used in the belief that the length of the muscle segment of the sphincter of Oddi extended beyond the duodenal wall and thus precluded endoscopic sphincterotomy. However, because patients with APBU have a sphincter of Oddi muscular segment that is normal in length and location in the duodenal wall, endoscopic therapy may be indicated. Total division of the sphincter by means of endoscopic sphincterotomy may offer a high probability of cure. Our results support this hypothesis. Ng et al.32 reported clinical improvement for 5 of 6 patients with APBU. Samavedy et al.33 performed endoscopic sphincterotomy of the common channel on 12 adult patients with recurrent pancreatitis and APBU. After endoscopic therapy 7 patients had no further pancreatitis, and 5 patients continued to have pancreatitis. Pancreatitis as a complication of therapy occurred in 1 of 9 patients but was mild and managed conservatively. Anatomic alterations of the pancreatic duct after pancreatic duct stent placement have been reported.34,35 Despite the tendency for these ductal changes to improve with time after stent removal, the long-term consequences of these stent-induced changes are unknown. We limit our duration of stenting to 7 to 10 days in an attempt to minimize the severity of ductal changes. Little information has been reported concerning the pancreatic ducts of patients with APBU. Some studies have documented abnormal pancreatographic findings,10,13,14,33 whereas others have found the pancreatic duct to be normal.36,37 In our study, 3 of 7 patients with choledochal cyst and sphincter of Oddi dysfunction had chronic pancreatitis; these patients were older (mean age 8.3 years) than those without chronic pancreatitis (mean age 4.2 years). Perhaps pancreatic duct changes become more severe through the years, as has been shown among adult patients with unexplained abdominal pain with chronic pancreatitis and sphincter of Oddi dysfunction38 and adult patients with recurrent pancreatitis and APBU.33 This study indicated that recurrent pancreatitis and APBU are associated with sphincter of Oddi dysfunction among children and adolescents. In these patients the sphincter of Oddi muscular segment is located within the duodenal wall. The results for this series indicate that endoscopic sphincterotomy is reasonably effective treatment of these patients. It is proposed that the mechanism for recurrent pancreatitis among patients with APBU is abnormal function of the sphincter of Oddi. 198
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This theory is supported by the excellent clinical response after endoscopic sphincterotomy found in this study. REFERENCES 1. Babbitt DP, Starshak RJ, Clemett AR. Choledochal cyst: a concept of etiology. AJR 1973;119:57-62. 2. Arima E, Akita H. Congenital biliary tract dilatation and anomalous junction of the pancreaticobiliary system. J Pediatr Surg 1979;14:9-15. 3. Guelrud M, Jaen D, Mendoza S, Torres P. Usefulness of endoscopic retrograde cholangiopancreatography in diagnosis of choledochal cysts in children. GEN 1989;43:9-12. 4. Suda K, Miyano T, Konuma I, Matsumoto M. An abnormal pancreatico-choledocho ductal junction in cases of biliary tract carcinoma. Cancer 1983;52:2086-8. 5. Kimura K, Ohto M, Saisho H, Unozawa T, Tsuchiya Y, Morita M, et al. Association of gallbladder carcinoma and anomalous pancreaticobiliary ductal union. Gastroenterology 1985;89: 1258-65. 6. Misra SP, Gulati P, Thorat VK, Vij JC, Anand BS. Pancreaticobiliary ductal union in biliary diseases: an endoscopic retrograde cholangiopancreatography study. Gastroenterology 1989;96:907-12. 7. Todani T, Watanabe Y, Fujii T, Ukemura S. Anomalous arrangement of the pancreaticobiliary ductal system in patients with a choledochal cyst. Am J Surg 1984;147:672-6. 8. Gibson LE, Haller JA. Acute pancreatitis associated with congenital cyst of the common bile duct. J Pediatr 1959;55:650-7. 9. Raffensperger BG, Given GZ, Warner RA. Fusiform dilatation of the common bile duct with pancreatitis. J Pediatr Surg 1973;8:907-10. 10. Mori K, Nagakawa T, Ohta T, Nakano T, Kadoya N, Kayahara M, et al. Acute pancreatitis associated with anomalous union of the pancreaticobiliary ductal system. J Clin Gastroenterol 1991;13:673-7. 11. Karp MP, Jewett TC, Cooney DR. Chronic relapsing pancreatitis in childhood caused by pancreaticobiliary ductal anomaly. J Pediatr Gastroenterol Nutr 1983;2:324-8. 12. Mohan P, Holcomb GW, Ziegler MM. Recurrent jaundice and pancreatitis in a child with pancreatobiliary duct anomalies. J Pediatr Gastroenterol Nutr 1994;18:386-90. 13. Kato O, Hattori K, Suzuki T, Tachino F, Yuasa T. Clinical significance of anomalous pancreaticobiliary union. Gastrointest Endosc 1983;29:94-8. 14. Guelrud M, Mujica C, Jaen D, Plaz J, Arias J. The role of ERCP in the diagnosis and treatment of idiopathic recurrent pancreatitis in children and adolescents. Gastrointest Endosc 1994;40:428-36. 15. Ponce J, Garrigues V, Sala T, Pertejo V, Berenguer J. Endoscopic biliary manometry in patients with suspected sphincter of Oddi dysfunction and in patients with cystic dilatation of the bile ducts. Dig Dis Sci 1989;34:367-71. 16. Take S, Okabe I, Morita K. Endoscopic manometric study of sphincter of Oddi for congenital bile duct dilatation [abstract in English]. Jpn J Pediatr Surg 1988;20:303-9. 17. Ochi T, Nakazawa S, Naito Y. Endoscopic manometry of the sphincter of Oddi and pancreatic duct in patients with anomalous arrangement of the pancreaticobiliary ductal system [Japanese]. J Jpn Soc Biliopancreatic Physiol 1989;5:27-35. 18. Matsumoto S, Tanaka M, Ikeda S, Yoshimoto H. Sphincter of Oddi motor activity in patients with anomalous pancreaticobiliary junction. Am J Gastroenterol 1991;86:831-4. 19. Todani T, Watanabe Y, Narusue M. Congenital bile duct cyst. Am J Surg 1977;134:263-9.
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20. Guelrud MG, Carr-Locke DL, Fox V. ERCP in pediatric practice: diagnosis and treatment. Oxford, UK: Isis Medical Media; 1997. 21. Guelrud M, Morera C, Rodriguez M, Prados JG, Jaen D. Normal and anomalous pancreaticobiliary union in children and adolescents. Gastrointest Endosc 1999;50:189-93. 22. Axon ATR, Classen M, Cotton PB, Cremer M, Freeny PC, Lees WR. Pancreatography in chronic pancreatitis: international definitions. Gut 1984;25:1107-12. 23. Sherman S, Troiano FP, Hawes RH, Lehman G. Sphincter of Oddi manometry: decreased risk of clinical pancreatitis with use of a modified aspirating catheter. Gastrointest Endosc 1990;36:462-6. 24. Guelrud M, Mendoza S, Rossiter G, Villegas MI. Sphincter of Oddi manometry in healthy volunteers. Dig Dis Sci 1990;35: 38-46. 25. Lehman GA, Sherman S, Nisi R, Hawes RH. Pancreas divisum: results of minor papilla sphincterotomy. Gastrointest Endosc 1993;39:1-8. 26. Cotton PB, Lehman GA, Vennes J, Geenen JE, Rusell RC, Meyers WC, et al. Endoscopic sphincterotomy complications and their management: an attempt at consensus. Gastrointest Endosc 1991;37:383-93. 27. Guelrud M, Mendoza S, Vicent S, Gomez M, Villalta B. Pressures in the sphincter of Oddi in patients with gallstones, common duct stones, and recurrent pancreatitis. J Clin Gastroenterol 1983;5:37-41. 28. Tanaka M, Ikeda S, Kawakami K, Nakayama F. The presence of a positive pressure gradient from pancreatic duct to choledochal cyst demonstrated by duodenoscopic microtransducer manometry: clue to pancreaticobiliary reflux. Endoscopy 1982;14:45-7. 29. Kinoshita H, Nagata E, Hirohashi K, Sakai K, Kobayashi Y. Carcinoma of the gallbladder with an anomalous connection between the choledochus and the pancreatic duct. Cancer 1984;54:762-9.
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30. Miyano T, Suruga K, Suda K. Abnormal choledocho-pancreatico ductal junction related to the etiology of infantile obstructive jaundice diseases. J Pediatr Surg 1979;14:16-26. 31. Sebesta C, Schmid A, Kier P, Ruckser R, Tiefengraber E, Rosen H, et al. ERCP and balloon dilatation is a valuable alternative to surgical biliodigestive anastomosis in the long common channel syndrome in childhood. Endoscopy 1995; 27:709-10. 32. Ng WD, Liu K, Wong MK, Long CK, Lee K, Chan YT, et al. Endoscopic sphincterotomy in young patients with choledochal dilation and a long common channel: a preliminary report. Br J Surg 1992;79:550-2. 33. Samavedy R, Sherman S, Lehman G. Endoscopic diagnosis and therapy of anomalous pancreatico-biliary junction [abstract]. Gastrointest Endosc 1997;45:AB164. 34. Kozarek RA. Pancreatic stents can induce ductal changes consistent with chronic pancreatitis. Gastrointest Endosc 1990;36:93-5. 35. Sherman S, Alvarez C, Robert M, Ashley SW, Reber HA, Lehman GA. Polyethylene pancreatic duct stent-induced changes in the normal dog pancreas. Gastrointest Endosc 1993;39:658-64. 36. Kimura K. Studies in 28 cases of congenital cystic dilatation of the common bile duct in adults: roentgenological features and union between the choledochus and the main pancreatic duct [abstract in English]. Jpn J Gastroenterol 1976;73: 401-14. 37. Sano H, Nakazawa S, Naito Y. Radiological study of the abnormal pancreaticocholangio-connection, with special reference to the “congenital choledochal cyst.” Gastroenterol Endosc 1981;23:1722-35. 38. Tarnasky PR, Hoffman B, Aabakken L, Knapple WL, Coyle W, Pineau B, et al. Sphincter of Oddi dysfunction is associated with chronic pancreatitis. Am J Gastroenterol 1997;92: 1125-9.
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