Therapeutic ERCP in the management of pancreatitis in children

Ronald K. Hsu, MD, FACG, FACP, Peter Draganov, MD, Joseph W. Leung, MD, FRCP, Paul R. Tarnasky, MD, Andy S. Yu, MD, Robert H. Hawes, MD, John T. Cunningham, MD, Peter B. Cotton, MD, FRCP
Sacramento and Pleasant Hill, California, and Charleston, South Carolina

Background: The use of diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP) is increasing in the management of pancreatobiliary diseases in children. Methods: Over a 32-month period, we performed 34 ERCP procedures for the treatment of pancreatitis in 22 children at two university hospitals. Demographics and clinical data and ERCP findings were documented. Clinical status was assessed 6 months before the first ERCP and 6 months after the last ERCP, according to general condition, severity and frequency of pain, and health care encounters (emergency department visits, clinic visits, and hospital admissions related to the pancreatitis). Results: Mean age of the patients was 10.7 years (range 1.5 to 17 years). Abdominal pain was the main presenting symptoms with hyperamylasemia and hyperlipasemia. Clinical diagnoses included acute pancreatitis (6), recurrent pancreatitis (5), and chronic pancreatitis (11). The mean followup was 16.4 months. Nine patients had sphincter manometry, with abnormal results leading to biliary sphincterotomy in 4. Fifteen patients underwent a total of 23 therapeutic ERCP procedures unrelated to sphincter dysfunction. There were 2 complications of 34 procedures (6%), both being mild pancreatitis after sphincter manometry. There were no deaths. There was a significant reduction in frequency (p < 0.01) and severity of pain (p < 0.01) after intervention. Patients without pancreatographic changes of chronic pancreatitis had the most marked clinical improvement (p < 0.05). In those with ductal changes of chronic pancreatitis, clinical improvement was not predicted by the extent of ductal changes. There was a significant decrease in health care encounters (p < 0.05) and improvement in general condition (p < 0.01) after endoscopic therapy, especially in those with a normal pancreatogram. Conclusions: Therapeutic ERCP is safe in pediatric patients with pancreatitis. Significant clinical improvement is achieved in patients with biliary or pancreatic stone disease. Prospective studies with long-term follow-up are needed to determine the impact of endoscopic therapy in patients with chronic pancreatitis and sphincter of Oddi dysfunction. (Gastrointest Endosc 2000;51:396-400.)

ERCP is an established modality for the diagnosis and treatment of pancreaticobiliary diseases in adults.1,2 Reported experience with diagnostic and therapeutic ERCP in pediatric patients is limited.3,4 This is due to the relatively low incidence of pancreaticobiliary diseases (e.g., calculi or neoplasia), limitations in the size of duodenoscopes, the need for general anesthesia, and the lack of highly trained and experienced endoscopists familiar with these
Received February 17, 1999. For revision May 18, 1999. Accepted September 29, 1999. From the University of California Davis Medical Center, Sacramento, California; Digestive Disease Center, Medical University of South Carolina, Charleston, South Carolina; Section of Gastroenterology, VA Northern California, Health Care System, Pleasant Hill, California. Presented at the Digestive Diseases Week, May 1997, Washington, D.C. (Gastrointest Endosc 1997;45:146). Reprint requests: Ronald Hsu, MD, FACG, FACP, University of California, Davis Medical Center, PSSB Room 3500, 4150 V St., Sacramento, CA 95817; e-mail: rkhsu@ucdavis.edu. 37/1/103335 doi:10.1067/mge.2000.103335 396 GASTROINTESTINAL ENDOSCOPY

special procedures in pediatric patients. With the refinement of technique and improvement in endoscope design, several studies have been reported with excellent results in the pediatric population,3-15 especially the management of biliary diseases (biliary sphincterotomy to facilitate drainage or stone extraction,4,5 stent placement,6,7 or stricture dilation).7 Experience with pancreatic therapy is limited.15-17 We report our experience with ERCP in the management of pancreatitis in pediatric patients.
PATIENTS AND METHODS Patients in this study included children who have undergone ERCP examination for the management of pancreatitis at two medical centers over a 32-month period (April 1994 to December 1996). The diagnosis of pancreatitis was made on the basis of clinical presentation, serum amylase/lipase levels, abdominal sonography, or CT findings. The demographic information, clinical data, ERCP findings, and complications were entered into a computer database system (GI Trac, Akron Systems Development, Charleston, S.C.). All available medical records were reviewed to verify the clinical history, results of laboratory
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Table 1. Impact of therapeutic ERCP

Score before ERCP General condition Severity Frequency Emergency department visit Clinic visit Admission to hospital 1.2 9.5 3.3 1.2 3.4 2.5 Score after ERCP 3.0 2.6 1.0 0 1.2 1.1 Change in scores +1.8 -6.8 -2.3 -1.4 -2.2 -1.4 p Value 0.004 0.002 0.002 0.02 0.03 0.02

Positive score indicates improvement in general condition; negative score indicates decrease in number of health care encounters or a decrease in the severity and frequency of attacks. Parameters are graded with Likert scales; all parameters reached statistical significance. General condition score: 0 = terrible, l = poor, 2 = fair, 3 = good, 4 = excellent; severity of pain range 0 to 10: 0 = no pain, 10 = unbearable; frequency of pain: 0 = never, l = yearly, 2 = monthly, 3 = weekly, 4 = daily, 5 = continuously. Number of health care encounters include: (1) emergency department visits, (2) clinic visits, (3) admissions to the hospital.

tests and radiologic imaging. A total of 34 ERCPs were performed on 22 patients. The mean age was 10.7 years (range 1.5 to 17 years). Abdominal pain was the main presenting symptom in all patients. The clinical diagnoses included acute pancreatitis in 6 cases, recurrent pancreatitis in 6, and chronic pancreatitis in 10. The following parameters were assessed for the period of 6 months before the first ERCP and 6 months after the last ERCP: general condition (Likert scale: 0 = terrible, 1 = poor, 2 = fair, 3 = good, 4 = excellent), severity of pain (0 = no pain, 10 = unbearable), frequency of pain (0 = never, l = yearly, 2 = monthly, 3 = weekly, 4 = daily, 5 = continuously), and number of health care encounters: (1) emergency room visits, (2) clinic visits, (3) admissions to the hospital. At the time of this report, the patients had been followed for a mean of 16.4 months (range 6 to 33 months). Informed consent was obtained after the risks and benefits of the procedure and alternative treatments were explained to the patient and key family members, in discussions which included the pediatrician, endoscopist, and surgeon where appropriate. Intravenous conscious sedation using a combination of midazolam, fentanyl, and droperidol was used in 7 patients (22%, age range 11 to 13 years) and general anesthesia was used in the remaining 15 patients (68%, age range 1.5 to 17 years). General anesthesia or conscious sedation was chosen at the discretion of the endoscopist. Blood pressure, pulse, and oxygen saturation were closely monitored during the examination. All ERCPs were performed using the standard adult videoduodenoscopes (JF-100, TJF-100; Olympus America, Inc., Melville, N.Y.) with standard (5F to 7F) accessories. Sphincterotomy was performed using standard instruments (Wilson-Cook Medical Inc., Winston-Salem, N.C.). Strictures were dilated using 4 to 6 mm diameter balloons (Max force; Microvasive Inc., Natick, Mass.) and stones were extracted with standard baskets (22Q or 23Q, Olympus). Biliary and/or pancreatic manometry was performed using the technique described by Sherman et al.18 with special catheters (Wilson-Cook); a basal pressure greater than 40 mm Hg was considered abnormal. Radiation exposure was kept to a minimum.
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The pancreatographic changes of chronic pancreatitis were defined using the Cambridge classification.19 Mild pancreatitis is defined as a normal main duct and more than 3 abnormal side branches; moderate pancreatitis has irregularities of the main duct and more than 3 abnormal side branches; severe pancreatitis has strictures and dilation involving the main pancreatic duct with or without stones or pseudocysts. The effects of therapeutic intervention on general condition and severity and frequency of pain score were assessed with analysis of variance by rank. Logistic regression was used to determine the predictors for clinical improvement.

RESULTS A total of 34 ERCPs were attempted on 22 patients. We achieved successful cannulation of the desired duct in all cases. Five patients had mild, 2 moderate, and 4 severe pancreatitis changes by pancreatography; 11 had a normal pancreatogram. The causes of pancreatitis were categorized as pancreatic or biliary. Fourteen patients had pancreatic causes: 6 pancreas divisum, 3 familial pancreatitis, 4 idiopathic pancreatitis, and 1 lymphomatous infiltration of the head of pancreas. Among the 6 patients with pancreas divisum, 2 had concomitant cystic fibrosis (ages 18 months and 13 years) and 1 had biliary sphincter hypertension. Of the 8 patients with biliary causes, 4 had choledochal cysts, 3 of whom (75%) had associated bile duct stones. Two patients had sphincter of Oddi dysfunction, confirmed by biliary manometry, and 2 had cholelithiasis. Fifteen patients underwent a total of 23 therapeutic ERCP procedures (range 1 to 3 per patient) unrelated to sphincter of Oddi dysfunction. There were 3 biliary sphincterotomies and 6 pancreatic sphincterotomies (2 major and 4 minor). Stone extraction was performed in 7 patients (4 biliary and 3 pancreatic). In 2 patients, pancreatic stones were extracted via
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Therapeutic ERCP in the management of pancreatitis in children

Table 2. Diagnosis, treatment, and outcomes in 22 children with pancreatitis

Age (yr) Diagnosis Manometry Treatment Cambridge class pancreatogram Improvement of Improvement of Improvement of Follow-up general condition pain severity pain frequency (mo)

3 3 4 14 14 1 9 8 11 13 14 15 5 14 17 17 9 18 6 12 12 16

CDC, stone B dil, sto CDC, stone B sph, sto CDC B ste CBD stone Bal sto SOD Abnormal B sph Divisum, CF Idiopathic Lymphoma B ste Divisum B sph, P maj sph Divisum, CF min sph, min ste SOD Abnormal* B sph, P major sph Idiopathic Normal Familial maj sph, min sph, sto Divisum Normal* min sph, min ste SOD, Divisum Abnormal min dil, min ste Idiopathic Idiopathic Normal Idiopathic Normal CDC, stone B sph sto Divisum Pancreatic stone Normal min sph, sto SOD Abnormal B sph, maj ste

0 0 0 0 0 0 0 0 0 0 1 1 1 1 1 2 2 2 3 3 3 3

Yes Yes No Yes Yes Yes Yes No Yes Yes No Yes Yes Yes Yes Yes Yes Yes Yes No No No

Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes No Yes Yes Yes No No Yes Yes Yes No No No

Yes Yes Yes Yes Yes No Yes Yes Yes Yes No No Yes Yes Yes No Yes Yes Yes No No No

17 12 24 31 9 8 33 9 33 10 9 11 22 9 25 21 4 4 14 21 12 19

CDC, Choledochocyst; SOD, sphincter of Oddi dysfunction; CF, cystic fibrosis; B, biliary; dil, dilation; sph, sphincterotomy; sto, stone extraction; ste, stenting; P, pancreatic; maj, major; min, minor. *Complication from mild pancreatitis.

the main papilla and in 1 through the minor papilla. Stents were used to facilitate pancreatic sphincterotomy in 4 patients (1 for major and 3 for minor papilla sphincterotomy) and for biliary drainage in 2 patients. Two patients underwent balloon dilation, one for a stenosed biliary sphincterotomy performed for stone extraction and one for a stenosed accessory sphincterotomy to facilitate drainage. Some patients required more than one procedure for stent removal, minor sphincterotomy, or assessment of therapy. Manometric studies on both sphincters were performed in 9 patients. Four (2 normal pancreas, 1 severe chronic pancreatitis, 1 divisum) were shown to have biliary sphincter hypertension (basal pressure > 40 mm Hg) and underwent biliary sphincterotomy. There was no case of pancreatic sphincter hypertension. Clinical outcome Endoscopic intervention resulted in significant improvements in all 6 outcome parameters (Table 1). Overall, there was significant clinical improvement in the frequency (p < 0.01) and the severity of pain (p < 0.01) after therapeutic intervention. There was a significant decrease in health care encounters (p < 0.05) and improvement in general condition (p < 0.01) after endoscopic therapy. Patients without pancreatographic changes of chronic pancreatitis were more likely to improve clinically compared with those with underlying ductal changes (p <
398 GASTROINTESTINAL ENDOSCOPY

0.05). This was especially true in patients with biliary pancreatitis. The most significant predictor for improvement in the severity and frequency of pain was the lack of pancreatogram changes (Table 2). Patients without ductal changes had the most significant clinical improvement. If changes of chronic pancreatitis were present, the severity did not correlate with clinical improvement after endoscopic therapy. Improvements were observed irrespective of the cause of pancreatitis, whether biliary or pancreatic. Five of the eight patients (63%) with an underlying pancreatic cause had significant clinical improvement (3 with pancreatic stones and 2 with pancreas divisum). Of the 6 patients with pancreas divisum, 5 presented with acute/recurrent and 1 with chronic relapsing pancreatitis. Minor duct sphincterotomy was performed in 3 patients, all of whom improved clinically. The patient with the chronic relapsing presentation had a pancreatic stone, and extraction resulted in a decrease in the frequency and the severity of attacks. Significant clinical improvement was achieved in 6 of 7 patients (86%) with biliary causes for pancreatitis including the 4 patients with choledochal cysts (3 patients had associated bile duct stones) and 1 patient with cholelithiasis. Three of the four patients with sphincter of Oddi dysfunction did not have any improvement in pain despite biliary sphincterotomy.
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Complications Procedure-related complications occurred after 2 of the 34 procedures (6%). Both patients had undergone sphincter manometry and developed mild pancreatitis. One patient had only a diagnostic manometry and the other had also undergone a biliary sphincterotomy. There was no procedure-related death. DISCUSSION Diagnostic and therapeutic ERCP is now an established procedure for adult patients with pancreaticobiliary disorders.1-3 Similar therapy has been attempted in pediatric patients.3-17 Improved endoscope and accessory designs have facilitated the development of ERCP procedures in children. In early reports on pediatric ERCP, cannulation was successful in 92% to 96% of cases.3-10 Cannulation was successful in all cases in our series. We used standard adult duodenoscopes in all patients. We found that diagnostic and therapeutic ERCP procedures can be successfully performed in children 1 year or older. Because the regular diagnostic scope with a 3.2 mm channel cannot accept 10F accessories, we prefer to use 5F accessories, such as a 5F sphincterotome, for smaller ductal systems. Conventional imaging, including US and CT, of the pancreas is less sensitive than ERCP. Magnetic resonance cholangiopancreatography is a noninvasive alternative but it lacks therapeutic capabilities.21,22 ERCP remains the standard for the evaluation of pediatric patients with clinical pancreatitis without an obvious cause. In skilled hands, ERCP is a safe procedure with a high diagnostic yield.1-17 In a recent study, ERCP altered therapy in 52% of pediatric patients with recurrent acute or chronic pancreatitis.27 The fact that most of our patients are referred after initial evaluation elsewhere explains the low percentage of patients (3 of 22, 14%) with normal ERCP studies as compared with the 50% of patients in other series.3-15 The progress in therapeutic ERCP has made a significant impact in the management of patients with pancreatitis, and in some situations ERCP is an alternative to surgical treatment. A variety of therapeutic procedures have been reported including sphincterotomy, balloon dilation of the papilla, balloon or basket stone extraction, as well as stent placement.7-11 The most dramatic response after endoscopic therapy is observed in patients with biliary pancreatitis; sphincterotomy and stone extraction are usually effective.10 As has been reported, we observed marked improvement in a patient who had stones
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associated with choledochal cyst.13 The stones in patients with choledochal cyst consist mainly of calcium carbonate and are thought to develop as a result of reflux of pancreatic juice into the dilated biliary system.13 The long-term effect of sphincterotomy in patients with choledochal cyst remains unclear. Although some speculate that the improved drainage from the common channel may prevent pancreaticobiliary reflux and thereby delay progression of the cystic changes, most pediatric surgeons recommend surgery for established cystic dilation because of the risk of malignancy.23 However, the residual dilated common duct stump after surgery is still at risk of pancreatic reflux and recurrent stone formation as occurred in one of our patients. Restenosis of the sphincterotomy may predispose to recurrent symptoms. Pediatric patients, like adult patients, can have pancreatitis secondary to sphincter of Oddi dysfunction. In general, they do not respond as well to endoscopic treatment, for which the complication rate tends to be higher than that for adults.24-26 Our results were similar to those of a multicenter study involving adult patients who underwent biliary sphincterotomy for sphincter of Oddi dysfunction.25 Randomized controlled studies may be difficult to conduct because of the low incidence of sphincter of Oddi among pediatric patients. The two complications in our series both occurred after biliary and pancreatic manometry. However, the precise determinations of the safety and efficacy of manometry and sphincterotomy in the pediatric population await further study. Some pediatric patients with pancreas divisum may have grossly dilated and irregular pancreatic ducts. This is likely a result of a relative obstruction to the flow of pancreatic juice. We observed clinical improvement after minor papillotomy in patients with pancreas divisum. However, long-term results of minor papilla papillotomy and dorsal pancreatic duct stent insertion are not available. Progressive changes including dilation and stricture formation in the pancreatic duct have been noted after pancreatic stent insertion.28,29 Overall, we observed significant clinical improvement in the frequency and the severity of pain after therapeutic intervention. There was a significant decrease in health care encounters and improvement in general condition after endoscopic therapy. Patients without pancreatographic changes of chronic pancreatitis were more likely to improve clinically compared with those with underlying ductal changes. This was especially the case in patients with biliary pancreatitis. However, in a few patients with severe ductal abnormalities, removal of panGASTROINTESTINAL ENDOSCOPY 399

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creatic stones did achieve improvement but the effects were not as pronounced. For the patients with ductal abnormalities of chronic pancreatitis, the degree of clinical improvement was not predictable based on the extent of the ductal changes. Patients who presented with chronic relapsing pancreatitis did not respond to therapy as well as did those with an acute presentation. The exception to this is the group of patients with biliary sphincter hypertension.
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