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Chronic relapsing pancreatitis in childhood
II r
Chronic relapsing pancreatitis in childhood We report 10 children with chronic relapsing pancreatitis. These patients can be divided into three groups, based on their clinical history, manifestations, and radiographic findings. Group t includes four patients with hereditary pancreatitis; these patients have had recurrent abdominal pain since early childhood, and have a positive family history for pancreatitis. Group 2 includes two patients with clinical and radiographic findings similar to those in patients with hereditary pancreatitis but without a family history of pancreatitis. Group 3 includes four patients with fibrosing pancreatitis who had symptoms and signs of obstructive jaundice. Our report emphasizes three points." (1) that chronic pancreatitis does occur in young children and is most commonly caused by hereditary pancreatitis or fibrosing pancreatitis; (2) that endoscopic retrograde cholangiopancreatiography is a safe and valuable tool for the study o f pancreatic and common bile ducts," and (3) that surgical intervention is indicated to drain the pancreatic duct in patients with hereditary pancreatitis, and sphincterotomy is an effective therapy for patients with fibrosing pancreatitis. (J PEOIATR 102:514, 1983)
Fayez K. Ghishan, M.D., Harry L. Greene, M.D., George Avant, M.D., James O'Neill, M.D., and Wallace Neblett, M.D. Nashville, Tenn.
CHRONIC RELAPSING PANCREATITIS is a chronic inflammatory disease characterized by acute exacerbations. Chronic relapsing pancreatitis has been thought of as a disease of adults, occurring most commonly secondary to alcohol abuse. ~ This perception has changed considerably, with the recognition of hereditary pancreatitis as a major cause of chronic pancreatitis in children and adolescents. 2 Other causes of chronic relapsing pancreatitis in childhood include malnutrition] hyperparathyroidism,4 cystic fibrosis, 5 and idiopathic fibrosing pancreatitis. 6 Chronic relapsing pancreatitis is often difficult to distinguish from acute relapsing pancreatitis secondary to biliary tract disease, 7 drugs, 8 hyperlipidemia,~ and congenital abnormalities of the sphincter of Oddi. l~ We report our experience with I0 children with chronic relapsing pancreatitis to emphasize that chronic pancreatitis does occur in young children and most commonly results from hereditary pancreatitis or fibrosing pancreatiFrom the Departments o f Pediatrics, Medicine, and Pediatric Surgery, Vanderbilt University Medical Center. Reprint requests." Fayez K. Ghishan, M.D., Associate Professor, Department of Pediatrics, Division o f Gastroenterology-Nutrition, Vanderbilt University Medical Center, Nashville, TN 37232.
514
TheJournalofPEDlATRICS
tis. Endoscopic retrograde cholangiopancreatography (ERCP) is the most specific method of evaluating the need for surgical intervention, Surgical therapy is indicated to drain the pancreatic duct, and appears to be the most appropriate treatment to prevent recurrent symptomatic pancreatitis in patients with hereditary pancreatitis. PATIENTS Ten patients with chronic relapsing pancreatitis were evaluated at Vanderbilt Children's Hospital. Their mean age was 8.8 years (range 3 to 16 years). Seven patients were boys. Eight patients had periumbilicaI or epigastric pain associated with vomiting. Four of the patients had jaundice, two without abdominal pain or vomiting. There was a positive family history for pancreatitis in four patients (patients 1, 2, 3, and 4). The mother of two patients (1 and 2) had had a pancreaticojejunostomy (Puestow procedure) at the age of 25 years. A maternal aunt, uncle, and grandfather of patient 3 had undergone surgery for pancreatitis. The father of patient 4 had pancreatic insufficiency and has insulin-dependent diabetes; his brother had partial pancreatectomy with pancreaticojejunostomy at the age of 18 years. No patient had a history of drug abuse.
Volume 102 Number 4
Chronic relapsing pancreatitis in childhood
5 15
Table 1. Laboratory data and radiographic findings in children with chronic relapsing pancreatitis
Patient
Serum a m y l a s e (IU/L)
Bilirubin (mg/dl)
Lipid panel
Ultrasound
1
1000
N
N
Increased echogenicity
2
1080
N
N
Poor visualization
3
1191
N
N
Increased echogenicity, large pseudocyst
4 5
670 190
N N
N N
Enlarged pancreas Normal pancreas
6
698
N
N
Calcification at head of pancreas
7
210
12/7
N
Enlarged, edematous pancreas
8
151
11/8.5
N
Dilated intrahepatic and extrahepatic ducts
9
120
4.5/2.5
N
Dilated intrahepatic duct
10
50
5.7/4.5
Type lib hyperlipidemia
Dilated intrahepatic duct, enlarged pancreas
Contrast study Dilated, saccular pancreatic duct or ERCP Mild dilation and beading of" pancreatic duct on ERCP Markedly dilated pancreatic duct with lucencies on ERCP Not done Dilated saccular pancreatic duct on ERCP Markedly dilated pancreatic duct on operative pancreatogram Narrowing of distal common bile duct on operative cholangiogram Obstruction at the distal common bile duct on transhepatic cholangiogram Narrowing of distal common bile duct on operative cholangiogram Narrowing of distal common bile duct on operative cholangiogram
Table II. Operative procedures, findings, and follow-up of eight patients with chronic relapsing pancreatitis
Patient
9 10
Pancreatic findings
Operation
Postoperative follow-up
Hard, contracted Hard, thickened with calcifications Hard, thickened Hard, thickened Fibrotic, nodular head of pancreas Fibrotic, nodular head of pancreas
Puestow Puestow Puestow Sphincterotomy Sphincterotomy Sphincterotomy Choledochoduodenostomy
Fibrotic, hard head of pancreas Fibrotic, nodular
Sphincterotomy Sphincterotomy
Well at 8 months Well at 2 years Well at 12 months Recurrent pain Well at 2 years Well at 12 months After revision at site of anastomosis, 5 months Well at 4 years Well at 4 years
RESULTS Table I depicts laboratory data and radiographic findings. Serum amylase level was high in all patients except patient 10; however, his amylase-creatinine clearance ratio was elevated to 8% (normal up to 4%). None of the patients had serum lipase determinations. All patients had normal serum calcium values, and the sweat chloride concentration was normal in the five patients in whom the test was done. Ultrasonography documented abnormalities in the pancreas or the biliary tract in nine of the 10 children studied. E R C P was performed in the hospital with
the patients under sedation with meperidine and diazepam, using the Olympus JFB2 side-angle duodenoscope. There were no complications in any of the children who underwent the procedure. E R C P was valuable in visualization of the pancreatic and biliary systems and in making the decision for surgery in patients 1, 2, 3, and 5. Figs. 1, 2, and 3 depict E R C P findings in patients 1, 2, and 3. Patient 6 had a markedly dilated pancreatic duct on operative pancreaticogram at the age of 2 years. In patients 7, 8, 9, and 10, with jaundice, visualization of the biliary tree was accomplished by either transhepatic cholangiogram (pa-
8 16
Ghishan et al.
The Journal o f Pediatrics April 1983
Fig. 1. Endoscopic retrograde cholangiopancreatography in patient 1, showing moderate dilation of main pancreatic duct with saccular changes. Fig. 3. ERCP in patient 3, showing markedly dilated main pancreatic duct along its entire course, with filling defects representing stones.
Fig. 2. ERCP in patient 2, showingminimal dilation and beading of main pancreatic duct.
tient 7) or operative cholangiogram. Narrowing or obstruction at the distal common bile duct was documented in all patients with jaundice. Table II depicts the operative procedure, findings, and follow-up of the eight patients who underwent surgery. Patients 1, 3, and 5 had markedly dilated pancreatic ducts and underwent pancreaticojejunostomy to drain the pancreatic ducts, with excellent results. These three patients remain asymptomatic for eight months, two years, and 12 months postoperatively, respectively. Patient 6 underwent
sphincterotomy, but continued to have recurrent abdominal pain. Patients 7, 8, 9, and 10 had obstructive lesions of the biliary tract secondary to a hard, fibrotic head of the pancreas. Sphincterotomy was successful in relieving the obstructive symptoms in three of the patients (patients 7, 9, and 10). Patient 8 underwent sphincterotomy and choledochoduodenostomy with revision at the site of anastomosis five months postoperatively, because of cholangitis; 12 months after the revision procedure the patient remains asymptomatic? ~ Based on the clinical history, symptoms, and laboratory findings, our 10 patients can be divided into three groups: those with hereditary pancreatitis; patients with clinical and ERCP findings similar to those of hereditary pancreatitis, but without a positive family history for pancreatitis; and those with fibrosing pancreatitis, with obstructive jaundice. Patients with hereditary pancreatitis had symptoms of recurrent abdominal pain at an early age. The abdominal pain in this group is usually associated with vomiting and occurs as frequently as every month. Based on our experience, we believe that ERCP is the best method to define abnormalities in the pancreatic ductal system in those patients. Surgical drainage of the Puestow type 12 was performed in those patients with adequate size of the pancreatic duct to perform pancreaticojejunostomy, and in no patient have subsequent symptoms occurred. Often these patients have
Volume 102 Number 4
calcified or noncalcified concretions in the pancreatic ducts, which require removal. Two of our patients had clinical symptoms of chronic relapsing pancreatitis and radiographic findings on the pancreatogram similar to those seen in patients with hereditary pancreatitis, but no family history of pancreatitis. One of the patients was a 15-year-old black girl (patient 5); hereditary pancreatitis has been described only in Caucasians. Whether these two patients represent a new mutation or their findings are secondary to repeated bouts of pancreatitis is unclear. One patient (patient 5) had remarkable improvement following the surgical procedure, with a 6.8 kg weight gain in one year. The other patient had sphincterotomy, but continued to have repeated episodes of abdominal pain, which required repeated hospitalization. Unfortunately, the family moved and no further follow-up is possible. It would have been of interest to repeat the pancreatogram, as he could be an ideal candidate for a surgical drainage procedure. Sphincterotomy alone is not satisfactory for patients with markedly dilated, saccular pancreatic ducts. A more radical procedure of the Puestow type would allow better drainage in such patients. Two of the four patients who had obstructive jaundice had no symptoms of abdominal pain; the other two had abdominal pain and vomiting along with jaundice. The total bilirubin concentration ranged between 4.5 and 12 mg/dl, with the conjugated fraction being greater than 50% in each patient. The obstruction site was defined in one patient by transhepatic cholangiogram (patient 8) and by intravenous cholangiogram in another (patient 9), and by operative cholangiogram in the other two patients (patients 7 and 10). In each case the common bile duct was dilated, with marked narrowing at the distal end caused by a hard fibrotic head of the pancreas. DISCUSSION Chronic pancreatitis is uncommon in the pediatric age group and has received little attention in pediatric textbooks. 13 Diagnosis is often difficult and is usually missed for several months or even years. In adults, chronic pancreatitis is usually secondary to alcohol abuse or biliary tract disease? ~7 Our experience indicates that hereditary pancreatitis and fibrosing pancreatitis are the two major etiologic factors causing chronic relapsing pancreatitis in the pediatric age group. The inheritance of hereditary pancreatitis is autosomal dominant. Forty affected kindreds, including 195 proved cases and 190 suspected cases, have been reported? 4 The cause of hereditary pancreatitis is not known. The findings of abnormal pancreatic ducts in the youngest patient studied (age 4 years) ~s and in our second patient (age 6
Chronic relapsing pancreatitis in childhood
51 7
years) suggest a basic structural or metabolic abnormality. Patients with familial pancreatitis or recurrent pancreatitis should undergo ERCP, because this is the only nonsurgical test capable of giving an accurate evaluation of pancreatic anatomy and pathology; ERCP is also capable of demonstrating the location and nature of obstructive lesions, as well as the most effective site for relief of that obstruction. This view is shared by Bluestein et al. I6 and by Creaghe et al? 7 If ERCP cannot be performed, operative cholangiopancreatography is probably the most practical approach to the problem. Without it, intelligent selection of the appropriate operative procedure cannot be made. Patients who develop recurrent pancreatitis should not be followed up for prolonged periods without having definitive studies of ductal anatomy to determine whether a surgical procedure is indicated and to avoid progression of fibrosis and deformity of the intrapancreatic ductal tree. It would appear from the follow-up studies in this series of patients that progressive disease can be arrested if obstruction of biliary and pancreatic flow can be relieved. Early surgery appears to offer two advantages: possible prevention of exocrine pancreatic insufficiency and diabetes, as seen in the father of patient 4, and normal life without frequent episodes of pain and hospitalization. Patients with fibrosing pancreatitis who have obstructive jaundice are candidates for percutaneous transhepatic cholangiography, or the biliary tree should be explored and defined by operative cholangiography. This group of patients resembles six adult patients described by Warshaw et al. ~8 with persistent obstructive jaundice secondary to common bile duct stenosis resulting from chronic pancreatitis. The liver biopsies in each of our patients showed bile duct proliferation with some increase in portal fibrosis, indicating obstructive jaundice. Serum amylase activity was elevated in three of the patients. In the fourth patient (patient 10) serum amylase activity was normal, with an elevated urinary amylase-creatinine clearnce ratio; however, he had hyperlipidemia, which is known to suppress the serum amylase level. ~9Three of the patients had sphincterotomy and remained asymptomatic for two to four years after the operative procedure. One patient had choledochoduodenostomy with sphincteroplasty, requiring revision at the site of anastomosis five months postoperatively because of recurrence of jaundice secondary to cholangitis. After revision of the anastomosis, the patient is doing well 12 months postoperatively. The choice of surgery in fibrosing pancreatitis depends on the anatomy of the pancreatic and biliary trees. If bile duct obstruction is complete, Roux-Y drainage is probably the safest form of management. In those instances in which the biliary tree appears to be normal and the pancreas is
5 18
Ghishan et al.
the site of severe fibrosing process, direct pancreatic d r a i n a g e is in order. The choice of procedure is dependent on the a n a t o m y encountered; either distal p a n c r e a t e c t o m y with drainage, as reported by Dural, z~ or split pancreaticojejunostomy, as described by Puestow, ~2 m a y be indicated. O u r experience indicates the need to consider fibrosing pancreatitis as a cause of obstructive jaundice in children. W h e n further a n a t o m i c information is needed for diagnosis, two modalities may be helpful: E R C P can be performed in children over the age of 5 years. Percutaneous t r a n s h e p a t i c cholangiography can be utilized in younger children, particularly when dilated biliary ducts are suspected from ultrasonography. E R C P has proved to be a safe procedure in our patients. T h e diagnostic value of E R C P in pancreatic disease in children has been recently supported by recent studies from C a n a d a TM and from England. 2~ REFERENCES 1. Sarles H, Tiscornia O: Ethanol and chronic calcifying pancreatitis. Med Clin North Am 58:1333, 1974. 2. Kattwinkel J, Lapey A, Di Sant'Agnese P, Edward W: Hereditary pancreatitis: Three new kindreds and a critical review of the literature. Pediatrics 51:55, 1973. 3. McDermott WV Jr, Bartlett MK, Culver PJ: Acute pancreatitis after prolonged fast and subsequent surfeit. N Engl J Med 254"379, 1956. 4. Carey MC, Fitzgerald O: Hyperparathyroidism associated with chronic pancreatitis in a family. Gut 9:700, 1968. 5. Schwachman H, Lebenthal E, Khaw KT: Recurrent acute pancreatitis in patients with cystic fibrosis with normal pancreatic functions. Pediatrics 55:86, 1975. 6. Williams TE, Sherman N J, Clatworthy HW: Chronic fibrosing pancreatitis in childhood: A cause of recurrent abdominal pain. Pediatrics 40:1019, 1967. 7. Acosta JM, Ledesma CL: Gallstone migration as a cause of acute pancreatitis. N Engl J Med 290:484, 1974.
The Journal o f Pediatrics April 1983
8. Parker P, Helinek G, Ghishan FK, Greene HL: Recurrent pancreatitis induced by va!proic acid: A case report and review of the literature. Gastroenterology 80:826, 1981. 9. Cameron JL, Capuzzi DM, Zuidema GD, et al: Acute pancreatitis with hyperlipidemia. Am J Med 56:482, 1974. 10. Cattell RB, Colcock BP, Pollack JL: Stenosis of the sphincter of Oddi. N Engl J Med 256:429, 1957. 1 I. Meneely RL, O'Neill J, Ghishan FK: Fibrosing pancreatitis. An obscure cause of painless obstructive jaundice: A case report and review of the literature. Pediatrics 67"136~ 1981. 12. Puestow CB, Gillesby W J: Retrograde surgical drainage of pancreatitis for chronic relapsing pancreatitis. Arch Surg 76:898, 1958. 13. di Sant'Agnesc PA: Pancreatitis. In Vaughan VC, McKay JM, Behrman RE, editors: Nelson's textbook of pediatrics. Philadelphia, 1979, WB Saunders, p 1135. I4. Girard RM, Dube S, Archambautt AP: Hereditary pancreatitis: Report of an affected Canadian kindred and review of the disease. Can Med Assoc J 112:576, 1981. 15. Cornet E, Dupon H, Hardy M, et al: Pancreatite chronique famiciale primitive avec estasies canalaires (6 cas operes). Rev Med Chir Mal Foie 38:1, 1963. 16. Bluestein PK, Gaskin K, Filler R, et al: Endoscopic retrograde cholangiopancreatography in pancreatitis in children and adolescents. Pediatrics 68:387, 1981. 17. Creaghe SB, Roseman DM, Saik RP: Biliary obstruction in chronic pancreatitis: Indications for surgical intervention. Am Surg 46"243, 1981. 18. Warshaw AL, Schapiro RH, Ferrucci JT, et al: Persistent obstructive jaundice, cholangitis, and biliary cirrhosis due to common bile duct stenosis in chronic pancreatitis. Gastroenterology 70:562, I976. 19. Lesser PB, Warshaw AL: Diagnosis of pancreatitis masked by hyperlipidemia. Am Intern Med 82:795, 1975. 20. Duval MC: Caudal pancreatico-jejunostomy for chronic pancreatitis. Ann Surg 140:775, 1954. 21. Cotton PB, Laage N J: Endoscopic retrograde cholangiopancreatography in children. Arch Dis Child 57:131, 1982.
Chronic relapsing pancreatitis in childhood We report 10 children with chronic relapsing pancreatitis. These patients can be divided into three groups, based on their clinical history, manifestations, and radiographic findings. Group t includes four patients with hereditary pancreatitis; these patients have had recurrent abdominal pain since early childhood, and have a positive family history for pancreatitis. Group 2 includes two patients with clinical and radiographic findings similar to those in patients with hereditary pancreatitis but without a family history of pancreatitis. Group 3 includes four patients with fibrosing pancreatitis who had symptoms and signs of obstructive jaundice. Our report emphasizes three points." (1) that chronic pancreatitis does occur in young children and is most commonly caused by hereditary pancreatitis or fibrosing pancreatitis; (2) that endoscopic retrograde cholangiopancreatiography is a safe and valuable tool for the study o f pancreatic and common bile ducts," and (3) that surgical intervention is indicated to drain the pancreatic duct in patients with hereditary pancreatitis, and sphincterotomy is an effective therapy for patients with fibrosing pancreatitis. (J PEOIATR 102:514, 1983)
Fayez K. Ghishan, M.D., Harry L. Greene, M.D., George Avant, M.D., James O'Neill, M.D., and Wallace Neblett, M.D. Nashville, Tenn.
CHRONIC RELAPSING PANCREATITIS is a chronic inflammatory disease characterized by acute exacerbations. Chronic relapsing pancreatitis has been thought of as a disease of adults, occurring most commonly secondary to alcohol abuse. ~ This perception has changed considerably, with the recognition of hereditary pancreatitis as a major cause of chronic pancreatitis in children and adolescents. 2 Other causes of chronic relapsing pancreatitis in childhood include malnutrition] hyperparathyroidism,4 cystic fibrosis, 5 and idiopathic fibrosing pancreatitis. 6 Chronic relapsing pancreatitis is often difficult to distinguish from acute relapsing pancreatitis secondary to biliary tract disease, 7 drugs, 8 hyperlipidemia,~ and congenital abnormalities of the sphincter of Oddi. l~ We report our experience with I0 children with chronic relapsing pancreatitis to emphasize that chronic pancreatitis does occur in young children and most commonly results from hereditary pancreatitis or fibrosing pancreatiFrom the Departments o f Pediatrics, Medicine, and Pediatric Surgery, Vanderbilt University Medical Center. Reprint requests." Fayez K. Ghishan, M.D., Associate Professor, Department of Pediatrics, Division o f Gastroenterology-Nutrition, Vanderbilt University Medical Center, Nashville, TN 37232.
514
TheJournalofPEDlATRICS
tis. Endoscopic retrograde cholangiopancreatography (ERCP) is the most specific method of evaluating the need for surgical intervention, Surgical therapy is indicated to drain the pancreatic duct, and appears to be the most appropriate treatment to prevent recurrent symptomatic pancreatitis in patients with hereditary pancreatitis. PATIENTS Ten patients with chronic relapsing pancreatitis were evaluated at Vanderbilt Children's Hospital. Their mean age was 8.8 years (range 3 to 16 years). Seven patients were boys. Eight patients had periumbilicaI or epigastric pain associated with vomiting. Four of the patients had jaundice, two without abdominal pain or vomiting. There was a positive family history for pancreatitis in four patients (patients 1, 2, 3, and 4). The mother of two patients (1 and 2) had had a pancreaticojejunostomy (Puestow procedure) at the age of 25 years. A maternal aunt, uncle, and grandfather of patient 3 had undergone surgery for pancreatitis. The father of patient 4 had pancreatic insufficiency and has insulin-dependent diabetes; his brother had partial pancreatectomy with pancreaticojejunostomy at the age of 18 years. No patient had a history of drug abuse.
Volume 102 Number 4
Chronic relapsing pancreatitis in childhood
5 15
Table 1. Laboratory data and radiographic findings in children with chronic relapsing pancreatitis
Patient
Serum a m y l a s e (IU/L)
Bilirubin (mg/dl)
Lipid panel
Ultrasound
1
1000
N
N
Increased echogenicity
2
1080
N
N
Poor visualization
3
1191
N
N
Increased echogenicity, large pseudocyst
4 5
670 190
N N
N N
Enlarged pancreas Normal pancreas
6
698
N
N
Calcification at head of pancreas
7
210
12/7
N
Enlarged, edematous pancreas
8
151
11/8.5
N
Dilated intrahepatic and extrahepatic ducts
9
120
4.5/2.5
N
Dilated intrahepatic duct
10
50
5.7/4.5
Type lib hyperlipidemia
Dilated intrahepatic duct, enlarged pancreas
Contrast study Dilated, saccular pancreatic duct or ERCP Mild dilation and beading of" pancreatic duct on ERCP Markedly dilated pancreatic duct with lucencies on ERCP Not done Dilated saccular pancreatic duct on ERCP Markedly dilated pancreatic duct on operative pancreatogram Narrowing of distal common bile duct on operative cholangiogram Obstruction at the distal common bile duct on transhepatic cholangiogram Narrowing of distal common bile duct on operative cholangiogram Narrowing of distal common bile duct on operative cholangiogram
Table II. Operative procedures, findings, and follow-up of eight patients with chronic relapsing pancreatitis
Patient
9 10
Pancreatic findings
Operation
Postoperative follow-up
Hard, contracted Hard, thickened with calcifications Hard, thickened Hard, thickened Fibrotic, nodular head of pancreas Fibrotic, nodular head of pancreas
Puestow Puestow Puestow Sphincterotomy Sphincterotomy Sphincterotomy Choledochoduodenostomy
Fibrotic, hard head of pancreas Fibrotic, nodular
Sphincterotomy Sphincterotomy
Well at 8 months Well at 2 years Well at 12 months Recurrent pain Well at 2 years Well at 12 months After revision at site of anastomosis, 5 months Well at 4 years Well at 4 years
RESULTS Table I depicts laboratory data and radiographic findings. Serum amylase level was high in all patients except patient 10; however, his amylase-creatinine clearance ratio was elevated to 8% (normal up to 4%). None of the patients had serum lipase determinations. All patients had normal serum calcium values, and the sweat chloride concentration was normal in the five patients in whom the test was done. Ultrasonography documented abnormalities in the pancreas or the biliary tract in nine of the 10 children studied. E R C P was performed in the hospital with
the patients under sedation with meperidine and diazepam, using the Olympus JFB2 side-angle duodenoscope. There were no complications in any of the children who underwent the procedure. E R C P was valuable in visualization of the pancreatic and biliary systems and in making the decision for surgery in patients 1, 2, 3, and 5. Figs. 1, 2, and 3 depict E R C P findings in patients 1, 2, and 3. Patient 6 had a markedly dilated pancreatic duct on operative pancreaticogram at the age of 2 years. In patients 7, 8, 9, and 10, with jaundice, visualization of the biliary tree was accomplished by either transhepatic cholangiogram (pa-
8 16
Ghishan et al.
The Journal o f Pediatrics April 1983
Fig. 1. Endoscopic retrograde cholangiopancreatography in patient 1, showing moderate dilation of main pancreatic duct with saccular changes. Fig. 3. ERCP in patient 3, showing markedly dilated main pancreatic duct along its entire course, with filling defects representing stones.
Fig. 2. ERCP in patient 2, showingminimal dilation and beading of main pancreatic duct.
tient 7) or operative cholangiogram. Narrowing or obstruction at the distal common bile duct was documented in all patients with jaundice. Table II depicts the operative procedure, findings, and follow-up of the eight patients who underwent surgery. Patients 1, 3, and 5 had markedly dilated pancreatic ducts and underwent pancreaticojejunostomy to drain the pancreatic ducts, with excellent results. These three patients remain asymptomatic for eight months, two years, and 12 months postoperatively, respectively. Patient 6 underwent
sphincterotomy, but continued to have recurrent abdominal pain. Patients 7, 8, 9, and 10 had obstructive lesions of the biliary tract secondary to a hard, fibrotic head of the pancreas. Sphincterotomy was successful in relieving the obstructive symptoms in three of the patients (patients 7, 9, and 10). Patient 8 underwent sphincterotomy and choledochoduodenostomy with revision at the site of anastomosis five months postoperatively, because of cholangitis; 12 months after the revision procedure the patient remains asymptomatic? ~ Based on the clinical history, symptoms, and laboratory findings, our 10 patients can be divided into three groups: those with hereditary pancreatitis; patients with clinical and ERCP findings similar to those of hereditary pancreatitis, but without a positive family history for pancreatitis; and those with fibrosing pancreatitis, with obstructive jaundice. Patients with hereditary pancreatitis had symptoms of recurrent abdominal pain at an early age. The abdominal pain in this group is usually associated with vomiting and occurs as frequently as every month. Based on our experience, we believe that ERCP is the best method to define abnormalities in the pancreatic ductal system in those patients. Surgical drainage of the Puestow type 12 was performed in those patients with adequate size of the pancreatic duct to perform pancreaticojejunostomy, and in no patient have subsequent symptoms occurred. Often these patients have
Volume 102 Number 4
calcified or noncalcified concretions in the pancreatic ducts, which require removal. Two of our patients had clinical symptoms of chronic relapsing pancreatitis and radiographic findings on the pancreatogram similar to those seen in patients with hereditary pancreatitis, but no family history of pancreatitis. One of the patients was a 15-year-old black girl (patient 5); hereditary pancreatitis has been described only in Caucasians. Whether these two patients represent a new mutation or their findings are secondary to repeated bouts of pancreatitis is unclear. One patient (patient 5) had remarkable improvement following the surgical procedure, with a 6.8 kg weight gain in one year. The other patient had sphincterotomy, but continued to have repeated episodes of abdominal pain, which required repeated hospitalization. Unfortunately, the family moved and no further follow-up is possible. It would have been of interest to repeat the pancreatogram, as he could be an ideal candidate for a surgical drainage procedure. Sphincterotomy alone is not satisfactory for patients with markedly dilated, saccular pancreatic ducts. A more radical procedure of the Puestow type would allow better drainage in such patients. Two of the four patients who had obstructive jaundice had no symptoms of abdominal pain; the other two had abdominal pain and vomiting along with jaundice. The total bilirubin concentration ranged between 4.5 and 12 mg/dl, with the conjugated fraction being greater than 50% in each patient. The obstruction site was defined in one patient by transhepatic cholangiogram (patient 8) and by intravenous cholangiogram in another (patient 9), and by operative cholangiogram in the other two patients (patients 7 and 10). In each case the common bile duct was dilated, with marked narrowing at the distal end caused by a hard fibrotic head of the pancreas. DISCUSSION Chronic pancreatitis is uncommon in the pediatric age group and has received little attention in pediatric textbooks. 13 Diagnosis is often difficult and is usually missed for several months or even years. In adults, chronic pancreatitis is usually secondary to alcohol abuse or biliary tract disease? ~7 Our experience indicates that hereditary pancreatitis and fibrosing pancreatitis are the two major etiologic factors causing chronic relapsing pancreatitis in the pediatric age group. The inheritance of hereditary pancreatitis is autosomal dominant. Forty affected kindreds, including 195 proved cases and 190 suspected cases, have been reported? 4 The cause of hereditary pancreatitis is not known. The findings of abnormal pancreatic ducts in the youngest patient studied (age 4 years) ~s and in our second patient (age 6
Chronic relapsing pancreatitis in childhood
51 7
years) suggest a basic structural or metabolic abnormality. Patients with familial pancreatitis or recurrent pancreatitis should undergo ERCP, because this is the only nonsurgical test capable of giving an accurate evaluation of pancreatic anatomy and pathology; ERCP is also capable of demonstrating the location and nature of obstructive lesions, as well as the most effective site for relief of that obstruction. This view is shared by Bluestein et al. I6 and by Creaghe et al? 7 If ERCP cannot be performed, operative cholangiopancreatography is probably the most practical approach to the problem. Without it, intelligent selection of the appropriate operative procedure cannot be made. Patients who develop recurrent pancreatitis should not be followed up for prolonged periods without having definitive studies of ductal anatomy to determine whether a surgical procedure is indicated and to avoid progression of fibrosis and deformity of the intrapancreatic ductal tree. It would appear from the follow-up studies in this series of patients that progressive disease can be arrested if obstruction of biliary and pancreatic flow can be relieved. Early surgery appears to offer two advantages: possible prevention of exocrine pancreatic insufficiency and diabetes, as seen in the father of patient 4, and normal life without frequent episodes of pain and hospitalization. Patients with fibrosing pancreatitis who have obstructive jaundice are candidates for percutaneous transhepatic cholangiography, or the biliary tree should be explored and defined by operative cholangiography. This group of patients resembles six adult patients described by Warshaw et al. ~8 with persistent obstructive jaundice secondary to common bile duct stenosis resulting from chronic pancreatitis. The liver biopsies in each of our patients showed bile duct proliferation with some increase in portal fibrosis, indicating obstructive jaundice. Serum amylase activity was elevated in three of the patients. In the fourth patient (patient 10) serum amylase activity was normal, with an elevated urinary amylase-creatinine clearnce ratio; however, he had hyperlipidemia, which is known to suppress the serum amylase level. ~9Three of the patients had sphincterotomy and remained asymptomatic for two to four years after the operative procedure. One patient had choledochoduodenostomy with sphincteroplasty, requiring revision at the site of anastomosis five months postoperatively because of recurrence of jaundice secondary to cholangitis. After revision of the anastomosis, the patient is doing well 12 months postoperatively. The choice of surgery in fibrosing pancreatitis depends on the anatomy of the pancreatic and biliary trees. If bile duct obstruction is complete, Roux-Y drainage is probably the safest form of management. In those instances in which the biliary tree appears to be normal and the pancreas is
5 18
Ghishan et al.
the site of severe fibrosing process, direct pancreatic d r a i n a g e is in order. The choice of procedure is dependent on the a n a t o m y encountered; either distal p a n c r e a t e c t o m y with drainage, as reported by Dural, z~ or split pancreaticojejunostomy, as described by Puestow, ~2 m a y be indicated. O u r experience indicates the need to consider fibrosing pancreatitis as a cause of obstructive jaundice in children. W h e n further a n a t o m i c information is needed for diagnosis, two modalities may be helpful: E R C P can be performed in children over the age of 5 years. Percutaneous t r a n s h e p a t i c cholangiography can be utilized in younger children, particularly when dilated biliary ducts are suspected from ultrasonography. E R C P has proved to be a safe procedure in our patients. T h e diagnostic value of E R C P in pancreatic disease in children has been recently supported by recent studies from C a n a d a TM and from England. 2~ REFERENCES 1. Sarles H, Tiscornia O: Ethanol and chronic calcifying pancreatitis. Med Clin North Am 58:1333, 1974. 2. Kattwinkel J, Lapey A, Di Sant'Agnese P, Edward W: Hereditary pancreatitis: Three new kindreds and a critical review of the literature. Pediatrics 51:55, 1973. 3. McDermott WV Jr, Bartlett MK, Culver PJ: Acute pancreatitis after prolonged fast and subsequent surfeit. N Engl J Med 254"379, 1956. 4. Carey MC, Fitzgerald O: Hyperparathyroidism associated with chronic pancreatitis in a family. Gut 9:700, 1968. 5. Schwachman H, Lebenthal E, Khaw KT: Recurrent acute pancreatitis in patients with cystic fibrosis with normal pancreatic functions. Pediatrics 55:86, 1975. 6. Williams TE, Sherman N J, Clatworthy HW: Chronic fibrosing pancreatitis in childhood: A cause of recurrent abdominal pain. Pediatrics 40:1019, 1967. 7. Acosta JM, Ledesma CL: Gallstone migration as a cause of acute pancreatitis. N Engl J Med 290:484, 1974.
The Journal o f Pediatrics April 1983
8. Parker P, Helinek G, Ghishan FK, Greene HL: Recurrent pancreatitis induced by va!proic acid: A case report and review of the literature. Gastroenterology 80:826, 1981. 9. Cameron JL, Capuzzi DM, Zuidema GD, et al: Acute pancreatitis with hyperlipidemia. Am J Med 56:482, 1974. 10. Cattell RB, Colcock BP, Pollack JL: Stenosis of the sphincter of Oddi. N Engl J Med 256:429, 1957. 1 I. Meneely RL, O'Neill J, Ghishan FK: Fibrosing pancreatitis. An obscure cause of painless obstructive jaundice: A case report and review of the literature. Pediatrics 67"136~ 1981. 12. Puestow CB, Gillesby W J: Retrograde surgical drainage of pancreatitis for chronic relapsing pancreatitis. Arch Surg 76:898, 1958. 13. di Sant'Agnesc PA: Pancreatitis. In Vaughan VC, McKay JM, Behrman RE, editors: Nelson's textbook of pediatrics. Philadelphia, 1979, WB Saunders, p 1135. I4. Girard RM, Dube S, Archambautt AP: Hereditary pancreatitis: Report of an affected Canadian kindred and review of the disease. Can Med Assoc J 112:576, 1981. 15. Cornet E, Dupon H, Hardy M, et al: Pancreatite chronique famiciale primitive avec estasies canalaires (6 cas operes). Rev Med Chir Mal Foie 38:1, 1963. 16. Bluestein PK, Gaskin K, Filler R, et al: Endoscopic retrograde cholangiopancreatography in pancreatitis in children and adolescents. Pediatrics 68:387, 1981. 17. Creaghe SB, Roseman DM, Saik RP: Biliary obstruction in chronic pancreatitis: Indications for surgical intervention. Am Surg 46"243, 1981. 18. Warshaw AL, Schapiro RH, Ferrucci JT, et al: Persistent obstructive jaundice, cholangitis, and biliary cirrhosis due to common bile duct stenosis in chronic pancreatitis. Gastroenterology 70:562, I976. 19. Lesser PB, Warshaw AL: Diagnosis of pancreatitis masked by hyperlipidemia. Am Intern Med 82:795, 1975. 20. Duval MC: Caudal pancreatico-jejunostomy for chronic pancreatitis. Ann Surg 140:775, 1954. 21. Cotton PB, Laage N J: Endoscopic retrograde cholangiopancreatography in children. Arch Dis Child 57:131, 1982.