A Little Girl with Pancreatitis

• Moderator's Introduction
• The Case
• Moderator's Questions
• Guest Discussant's Reply
• Moderator's Comments
• Acknowledgements
• Guest Discussant's Suggested Reading

Moderator's Introduction

For our first case in this Evidence-Based Endoscopy series, I am delighted to welcome an old friend and mentor, Dr. Richard (Dick) Kozarek. As you will see, I took pity and give him an “easy” case!

The Case

A 4œ-year-old girl has been having recurrent attacks of abdominal pain and vomiting since the age of 2 years. A typical episode would last 2 - 3 days, with vomiting a prominent feature. She has had these episodes on an almost monthly basis. She was transferred to Duke University Medical Center with vomiting, dehydration, and abdominal pain of 1 week's duration.

The patient looked relatively well, but was mildly febrile (37.8 °C). She weighed 16 lb. Apart from epigastric tenderness, her examination was unremarkable. Automated blood count (ABC) and electrolytes were normal, but her serum lipase was elevated at 1358 IU/l (normal < 208), with a serum amylase of 95 IU/l (normal < 110). Transabdominal ultrasound revealed “marked dilatation of the pancreatic duct (6 mm)”. A computed tomography (CT) scan confirmed this, but otherwise the pancreas appeared normal (no calcifications or cysts). Endoscopic retrograde cholangiopancreatography (ERCP) was requested. This was performed under general anesthesia using a pediatric duodenoscope. Esophagogastroduodenoscopic (EGD) findings were normal, as were cholangiographic findings (Figure [1]). On the basis of the appearances of the pancreatic duct, imaged through the main papilla (Figure [2]), minor papilla cannulation was attempted. Intravenous secretin injection was needed to identify the orifice, through which contrast was injected (Figure [3]).

Moderator's Questions

I asked Dr. Kozarek to review this case summary and the radiographs shown (Figures [1] [2] [3] ), and invited him to address the following questions:

1. Presented with this patient, what would be your “thought process” regarding this child's investigation and management?

2. Given the appearance of the pancreatogram, how would you proceed?

3. How would you follow this child's progress, and can you offer a prognosis?

Guest Discussant's Reply

This four-and-a-half-year-old child has had cyclical abdominal pain and vomiting for the past 2 years. Although children at this age can develop mundane conditions, including peptic ulcer disease or florid chalasia (gastroesophageal reflux), the finding of hyperlipasemia by itself suggests recurrent attacks of pancreatitis. Without benefit of the abdominal ultrasound and CT scan demonstrating ductal dilation, one can say that common causes of pancreatitis would include biliary stone disease, as well as numerous congenital plumbing variants in a pediatric patient. The latter would include annular pancreas, anomalous pancreaticobiliary union, duodenal web or diaphragm, and gastric or duodenal duplication, which is not infrequently connected to an isolated pancreatic duct. The differential diagnosis would also include hereditary metabolic disorders, including cystic fibrosis in particular, and, despite the apparent absence of family history, hereditary pancreatitis.

As undertaken in this child, an abdominal ultrasound followed by a CT scan would be the initial work-up, although concomitant diagnostic endoscopy or upper gastrointestinal series might have proven useful had gross pancreatic ductal dilation not been noted. Most pediatricians in this setting would also have screened sweat chlorides in order to rule out an atypical case of cystic fibrosis.

Once gross ductal dilation was noted on noninvasive imaging, it was imperative to define both ductal and duodenal anatomy. Although the latter could have been accomplished with magnetic resonance cholangiopancreatography (MRCP), my approach would have been similar to that undertaken at Duke University, as ERCP is not only more sensitive for subtle abnormalities but also affords opportunities for therapy: sphincterotomy and stone retrieval for pancreaticobiliary calculi and some forms of anomalous pancreaticobiliary drainage, marsupialization of a duplication cyst, or transient stent placement for a significant ductal stenosis.

The ERCP, of course (Figure [1]), shows a normal biliary tree and a pancreas divisum with moderately severe chronic pancreatitis changes (ductal dilation, beading, strictures, and side branch ectasias). Figure [2] is an enlarged image (compare the vertebral sizes between Figures [2] and [3]) of the ventral pancreatic duct injected through the major papilla, and is seen relative to the dorsal pancreatic duct injected through the minor papilla (Figure [3]).

What can we say with certainty about this case? For one thing, the pancreas divisum, occurring in 5 - 7 % of the population and hotly debated as a cause of relapsing pancreatitis, chronic pancreatitis, and even chronic pancreatic type pain, is incidental to this child's pancreatitis, given its distribution. Secondly, this is not “classic” cystic fibrosis in which the pancreaticobiliary tree is often atretic and filled with tenacious mucus. Nevertheless, approximately 20 - 25 % of patients with idiopathic pancreatitis and pancreas divisum in conjunction with relapsing pancreatitis have mutations in their cystic fibrosis transmembrane regulator (CFTR) gene, without other manifestations of cystic fibrosis. This gene should be checked, and chromosomal analysis for “hereditary” pancreatitis should be carried out, as well as a more mundane blood test to rule out significant hypercalcemia.

What to do now is the endoscopist's dilemma. Although we are limited to a single dorsal pancreatogram, it appears that there is a 4 - 5 mm calculus in the head of the duct. If this is substantiated on additional films, an accessory papillotomy, stone clearance, and temporary prosthesis placement are all technically feasible in this age group, and in previously published experience from our center, this approach is often associated with reduction in pain, resolution of relapsing pancreatitis, and significant growth spurts in affected children. When this is undertaken for hereditary pancreatitis, these stones return after 3 - 5 years in most individuals, but are readily extracted unless they are allowed to calcify and completely obstruct the dominant duct.

Obviously, plumbing issues are not approached in isolation, and pancreatic enzyme supplements, with or without concomitant acid-inhibiting medications and dietary modifications, may be required. Genetic evaluation is a must. As such, the long-term prognosis is often best arrived at by defining the underlying metabolic defect. Endoscopic therapy may ultimately give way to gene therapy but, at a minimum, delineation of these defects may explain subtle sibling symptoms, and reproductive risks for parents and patients alike.

Moderator's Comments

Dr. Kozarek is quite correct in thinking that we proceeded to perform minor papillotomy in this young lady with pancreas divisum. The small filling defect could not be confirmed as a stone on subsequent images. Therefore, a 5-Fr, 3-cm (between the flaps) single pigtail stent without flanges was placed across the minor papilla and a needle knife papillotomy performed by cutting down on to it. The procedure itself was uncomplicated, and there was no post-ERCP pancreatitis. The patient was discharged home the following day on a low fat diet and pancreatic enzyme supplements. Fluoroscopy 1 week later showed that the stent had migrated into the gut and been passed spontaneously. The patient had a further brief hospitalization 3 weeks later, with a mild episode of pancreatitis which settled quickly. She has subsequently been asymptomatic for over 6 months, her longest symptom-free interval since she began to have attacks of abdominal pain, nausea, and vomiting.

As indicated by Dr. Kozarek, a genetic cause for pancreatitis must be a serious consideration in a 4-year-old. Sweat chloride testing for cystic fibrosis was negative. However, a research laboratory test for CFTR mutations strongly suggests that this little girl does indeed have one of the commoner pancreatitis-associated CFTR defects. We await confirmation of this finding by a reference laboratory.

At present, there is no specific therapy for CFTR mutations. Should siblings, parents or other family members be tested? This is a difficult question! Patients being assessed for genetic abnormalities - whether or not a “cure” or treatment is available - should probably be offered professional genetic counseling before they are tested.

A vexing question raised by informed spectators at the time of this patient's ERCP was whether or not the main pancreatic sphincter should also be cut, given the clearly abnormal ventral pancreatic duct. The endoscopist (JB) felt that he had no data on which to base such an intervention, and was concerned that two needle knife papillotomies at one “sitting” might mean twice the risk of post-ERCP pancreatitis! It is fair to say that performing a minor papillotomy in a 4-year-old child is a distinctly uncommon event; to paraphrase the old saying about a prisoner contemplating his execution in the morning, “it concentrates the mind wonderfully”! It was with some trepidation that the Duke biliary team went to check on this young patient some hours after the ERCP, and an enormous relief to find her fast asleep, tightly clutching her favorite teddy bear.

Dr. Kozarek was asked whether or not both major and minor duodenal papillas should have been cut in this case, given the disease seen in both ventral and dorsal pancreatic ducts. He replied that he would have only cut the minor papilla - as we did - on the first ERCP. There would be “plenty of time later” to think about cutting the main papilla if there appeared to be no benefit from minor papillotomy.

Acknowledgements

Thanks to Dr. William Treem, MD, Chief of Pediatric Gastroenterology at Duke University Medical Center, for allowing us to present his patient, and to Dr. John Cohn, MD, Associate Professor of Medicine in the Division of Gastroenterology at Duke, for his insights into CFTR and cationic trypsinogen testing.

Guest Discussant's Suggested Reading

• 1 Mergener K, Baillie J. Chronic pancreatitis.  Lancet. 1997;  350 1379-1385
  CrossrefPubMedSearch in Google Scholar
• 2 Taggo F P, Tarnasky P R, Chandler J, et al. Multidisciplinary approach to the treatment of pediatric pancreaticobiliary disorders.  J Pediatr Surg. 1997;  32 158-165
  CrossrefPubMedSearch in Google Scholar
• 3 Guelrud M, Mujica C, Jaen D, et al. The role of ERCP in the diagnosis and treatment of idiopathic recurrent pancreatitis in children and adolescents.  Gastrointest Endosc. 1994;  40 428-436
  CrossrefPubMedSearch in Google Scholar
• 4 Lehman G A, Sherman S. Diagnosis and therapy of pancreas divisum.  Gastrointest Endosc Clin N Am. 1998;  8 55-77
  Search in Google Scholar
• 5 Kozarek R A, Ball T J, Patterson D J, et al. Endoscopic approach to pancreas divisum.  Dig Dis Sci. 1995;  40 1974-1981
  PubMedSearch in Google Scholar
• 6 Jacob L, Geenen J E, Catalano M T. Clincal presentation and short-term outcome of endoscopic therapy of patients with incomplete pancreas divisum.  Gastrointest Endosc. 1999;  49 53-57
  PubMedSearch in Google Scholar
• 7 Kozarek R A, Christie D, Barclay G. Endoscopic therapy of pancreatitis in the pediatric population.  Gastrointest Endosc. 1993;  39 665-669
  PubMedSearch in Google Scholar
• 8 Kozarek R A, Traverso L W. Endotherapy for chronic pancreatitis.  Int J Pancreatol. 1996;  19 93-102
  PubMedSearch in Google Scholar
• 9 Sherman S, Lehman G A. Endoscpic therapy of pancreatic disease.  Gastroenterologist. 1997;  5 262-267
  PubMedSearch in Google Scholar
• 10 NIH Consensus Conference. Genetic testing for cystic fibrosis.  Arch Intern Med. 1999;  159 1529-1539
  CrossrefPubMedSearch in Google Scholar
• 11 Cohn J A, Freedman K J, Silverman L M, et al. CFTR mutations predispose to chronic pancreatitis without cystic fibrosis lung disease.  Gastroenterology. 1997;  112 434
  PubMedSearch in Google Scholar
• 12 Choudari C P, Fogel E L, Sherman S. Pancreas divisum, pancreatitis and CFTR mutations.  Gastrointest Endosc. 1999;  49 187
  PubMedSearch in Google Scholar
• 13 Sossenheimer M J, Aston C E, Preston R A, et al. Clinical characteristics of hereditary pancreatitis in a large family, based on high risk haplotype.  Am J Gastroenterol. 1997;  92 1113-1116
  PubMedSearch in Google Scholar
• 14 Whitcomb D C, Gorny M C, Preston R A, et al. Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene.  Nat Genet. 1996;  14 141-145
  CrossrefPubMedSearch in Google Scholar
• 15 Lowenfals A B, Maisonneuve P, Cavallini G, et al. Prognosis of chronic pancreatitis: an international multicenter trial.  Am J Gastroenterol. 1999;  89 1467-1471
  PubMedSearch in Google Scholar
• 16 Cohn J A, Friedman K J, Noone P G, et al. Relation between mutations of the cystic fibrosis gene and idiopathic pancreatitis.  N Engl J Med. 1998;  339 687-688
  CrossrefPubMedSearch in Google Scholar

John BaillieM.B., Ch.B., F.R.C.P. 

Biliary Service Duke University Medical Center

Durham

North Carolina

USA


Fax: +1-919-684-4695

Email: baill001@mcduke.edu

R. A. KozarekM.D. 

The Virginia Mason Clinic

Seattle

Washington

USA


Fax: + 1-206-223-6379

Guest Discussant's Suggested Reading

• 1 Mergener K, Baillie J. Chronic pancreatitis.  Lancet. 1997;  350 1379-1385
  CrossrefPubMedSearch in Google Scholar
• 2 Taggo F P, Tarnasky P R, Chandler J, et al. Multidisciplinary approach to the treatment of pediatric pancreaticobiliary disorders.  J Pediatr Surg. 1997;  32 158-165
  CrossrefPubMedSearch in Google Scholar
• 3 Guelrud M, Mujica C, Jaen D, et al. The role of ERCP in the diagnosis and treatment of idiopathic recurrent pancreatitis in children and adolescents.  Gastrointest Endosc. 1994;  40 428-436
  CrossrefPubMedSearch in Google Scholar
• 4 Lehman G A, Sherman S. Diagnosis and therapy of pancreas divisum.  Gastrointest Endosc Clin N Am. 1998;  8 55-77
  Search in Google Scholar
• 5 Kozarek R A, Ball T J, Patterson D J, et al. Endoscopic approach to pancreas divisum.  Dig Dis Sci. 1995;  40 1974-1981
  PubMedSearch in Google Scholar
• 6 Jacob L, Geenen J E, Catalano M T. Clincal presentation and short-term outcome of endoscopic therapy of patients with incomplete pancreas divisum.  Gastrointest Endosc. 1999;  49 53-57
  PubMedSearch in Google Scholar
• 7 Kozarek R A, Christie D, Barclay G. Endoscopic therapy of pancreatitis in the pediatric population.  Gastrointest Endosc. 1993;  39 665-669
  PubMedSearch in Google Scholar
• 8 Kozarek R A, Traverso L W. Endotherapy for chronic pancreatitis.  Int J Pancreatol. 1996;  19 93-102
  PubMedSearch in Google Scholar
• 9 Sherman S, Lehman G A. Endoscpic therapy of pancreatic disease.  Gastroenterologist. 1997;  5 262-267
  PubMedSearch in Google Scholar
• 10 NIH Consensus Conference. Genetic testing for cystic fibrosis.  Arch Intern Med. 1999;  159 1529-1539
  CrossrefPubMedSearch in Google Scholar
• 11 Cohn J A, Freedman K J, Silverman L M, et al. CFTR mutations predispose to chronic pancreatitis without cystic fibrosis lung disease.  Gastroenterology. 1997;  112 434
  PubMedSearch in Google Scholar
• 12 Choudari C P, Fogel E L, Sherman S. Pancreas divisum, pancreatitis and CFTR mutations.  Gastrointest Endosc. 1999;  49 187
  PubMedSearch in Google Scholar
• 13 Sossenheimer M J, Aston C E, Preston R A, et al. Clinical characteristics of hereditary pancreatitis in a large family, based on high risk haplotype.  Am J Gastroenterol. 1997;  92 1113-1116
  PubMedSearch in Google Scholar
• 14 Whitcomb D C, Gorny M C, Preston R A, et al. Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene.  Nat Genet. 1996;  14 141-145
  CrossrefPubMedSearch in Google Scholar
• 15 Lowenfals A B, Maisonneuve P, Cavallini G, et al. Prognosis of chronic pancreatitis: an international multicenter trial.  Am J Gastroenterol. 1999;  89 1467-1471
  PubMedSearch in Google Scholar
• 16 Cohn J A, Friedman K J, Noone P G, et al. Relation between mutations of the cystic fibrosis gene and idiopathic pancreatitis.  N Engl J Med. 1998;  339 687-688
  CrossrefPubMedSearch in Google Scholar

John BaillieM.B., Ch.B., F.R.C.P. 

Biliary Service Duke University Medical Center

Durham

North Carolina

USA


Fax: +1-919-684-4695

Email: baill001@mcduke.edu

R. A. KozarekM.D. 

The Virginia Mason Clinic

Seattle

Washington

USA


Fax: + 1-206-223-6379