Chronic Pancreatitis in Children: Focus on Pancreatic Divisum & Genetic Pancreatitis

Case Conference Joanna Yeh

October 27, 2011

Case Presentation

• 7 yo girl admit to CHLA in April 2011 for acute onset emesis and pain

• Pain was periumbilical, causing her to be sent home from school

• Pain seems to be worse with food and liquids

• She had low grade temperatures x 1 day at presentation

• Patient has had abdominal pain episodes for 2 years; diagnosed with “constipation”

• Prior to admission, patient had been seen by PMD and told she had “stomach flu”

• When family history was elicited, dad has hereditary pancreatitis (PRSSI and CFTR)

• Remaining H&P was non contributory

Further History

Physical Exam

• Temp 100.1 HR 121 BP 102/58 RR 20 Sat 99% RA

• Wt. 20 kg

• Abd: soft, non tender to deep palpation throughout but endorses intermittent subjective pain. Not distended, no masses. No HSM.

• Skin: no rashes, no papules

• Remaining exam normal

• At CHLA, labs notable for normal CBC, normal CMP, lipase 1030

• Abdominal ultrasound notable for prominent pancreatic duct, 3-4 mm, common bile duct 1 mm

• Abdominal CT was done with IV and PO contrast that showed no pancreatic inflammation

• MR cholangiopancreatography (MRCP) revealed pancreas divisum

Labs & Imaging

Chronic Pancreatitis Definition

• Progressive inflammatory disease of pancreas

• Characterized by irreversible structural changes that result in irreversible exocrine and endocrine pancreatic insufficiency

Etiology

• Congenital anomalies

• Genetic

• Toxic/metabolic

• Autoimmune

• Idiopathic

Congenital anomalies

• Pancreatic divisum • Choledochal cysts • Pancreatic duct duplication • Renal cysts • Congenital pancreatic cysts • Annular pancreas

Embryology

Anatomy

Different types of pancreas divisum

Divisum

• Diagnosis: – Endoscopic ultrasonography

– ERCP (endoscopic retrograde cholangiopancreatography)

– MRCP (magnetic resonance cholangiopancreatography)

• Divisum can be the sole etiology of acute or chronic pancreatitis, but not always

• Incidental divisum: 5-10% lifetime risk of developing pancreatitis

• Malignancy risk highest in dorsal pancreas

Divisum Treatment

• Endoscopy / Therapeutic ERCP

– Spincterotomy

– Papillary dilation

– Stent insertion

• Surgical

– Minor papilla spincterotomy

– Puestow procedure (pancreaticojejunostomy)

– Pancreatectomy

Genetic Pancreatitis

• PRSS1

cationic trypsinogen

• SPINK1

serine protease inhibitor Kazal type 1

• CFTR cystic fibrosis transmembrane conductance regulator

• Chymotrypsin C

Who should be tested?

– A family history of recurrent acute pancreatitis, idiopathic chronic pancreatitis, or childhood pancreatitis without a known cause

– Relatives known to carry mutations associated with hereditary pancreatitis

– Recurrent acute attacks of pancreatitis for which there is no identifiable cause

– An unexplained documented episode of pancreatitis as a child

– Idiopathic chronic pancreatitis, particularly when the onset of pancreatitis occurs before age 25

Genetic Pancreatitis: Management

• Small meals, low fat, good hydration

• Avoidance of alcohol and tobacco

• Monitor exocrine and endocrine function

– Enzyme supplementation

– Diabetes management

• Pancreaticojejunostomy / Pancreatectomy

• Islet cell autotransplantation

Pancreatic Enzymes

• Child<4 yo: 1000 units lipase/kg/meal

• Child>4 yo: 500 units lipase/kg/meal

• Max: 2500 units lipase/kg/meal

• Snack dose is about ½ of meal dose

• Enteric coated microspheres

• At UCLA inpatient, we have Zenpep (5) and Zenpep (20)

• Others: Creon, Pancreacarb, Pancreaze

• If sprinkle into food, should be relatively acidic to avoid dissolving enteric coating (applesauce, banana, sweet potato)

Patient Update

• Hospitalized in Oct 2011 to Santa Monica for another episode of pancreatitis

• Father has since undergone pancreatectomy and islet cell transplantation

• Her genetic testing was positive for CFTR (dad is positive for CFTR and PRSSI)

• Dr. Farrell is following her and may consider EUS in future. No plans for ERCP.

References • Takuma, et al, “Pancreatic disease associated with pancreas divisum,” Digestive Surgery, 2010, 27,

pg 144-8.

• Dumont, et al, “Pancreas divisum and the dominant dorsal duct syndrome,” Annals of Surgery, Jan 2005, 130, 1, pg 5-14.

• Bellin, et al, ‘Outcome After Pancreatectomy and Islet Autotransplantation in a Pediatric Population,” Journal of Pediactirc Gastroenterology and Nutrition, 2008, 47, p 37-44.

• “Surgical Treatment of Pancreas Divisum Causing Chronic Pancreatitis,” Journal of Gastrointestinal Surgery, May 2005, 9, 5, pg 710-5.

• Dray, et al, “Association of Pancreas Divisum and Recurrent Acute Pancreatitis,” Pancreas, 2007, 35, pg 90-3.

• Bhardwaj, et al, “A RCT of antioxidant supplementation for pain relief in patients with chronic pancreatitis,” Gastroenterology, 2009, 136, 1, pg 149.

• Kamisawa, et al, “Pancreatitis associated with congenital abnormalities of the pancreaticobiliary system,” Hepatogastroenterology, 2005, 52, 61, pg 223-9.

• Rosendahl, et al, “Hereditary chronic pancreatitis,” Orphanet Journal of Rare Diseases,” Jan 2007, 2, 1.

• Witt H, “Genetics of pancreatitis: a guide for clinicians,” Digestive Diseases, 2010, 28, 6, pg 702-8.

• Ferrone, et al, “Panreatic enzyme pharmacotherapy,” Pharmacotherapy, 2007, 27, 6, pg 910-20.