Pediatric Pancreatic Lesions

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1 Pediatric Pancreatic Lesions Pediatric Surgery Grand Rounds 9 October 2013 Tim Weatherall, PGY2 The University of Tennessee Health Science Center Memphis, TN

2 Disclosures No financial interests to disclose

3 I'm tired of all this nonsense about beauty being only skin-deep. That's deep enough. What do you want, an adorable pancreas? -Jean Kerr

4 Pancreatic Embryology Arises in week 5 of gestation Paired evaginations of the primitive foregutdorsal and ventral Fuse at gestational week 7

5

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7 Pancreatic Physiology Exocrine: pancreatic juice containing digestive enzymes Endocrine: insulin, glucagon, somatostatin, pancreatic polypeptide

8 Congenital Anomalies Ectopic pancreatic rests Annular pancreas Pancreas divisum Cystic fibrosis

9 Ectopic pancreatic rests Abnormally located pancreatic tissue Frequently encountered along foregut derivatives Found in ~2% of autopsy series

10 Ectopic Pancreatic Rests

11 Ectopic Pancreatic Rests Generally benign Excise if patient is symptomatic from symptoms of obstruction

12 Annular Pancreas

13 Annular Pancreas Duodenum obstructed by encircling pancreatic tissue Duodenal atresia, malrotation and trisomy 21 often found in combination Usual presentation bilious vomiting or other symptoms of obstruction Treatment: duodenoduodenostomy or duodenojejunostomy

14 Annular Pancreas

15 Annular Pancreas Double-bubble sign on plain film Non-specific finding

16 Pancreas Divisum

17 Pancreas Divisum Present in ~7% in autopsy series Majority of exocrine secretions drain through minor duct and papilla Relative obstruction may lead to recurring episodes of pancreatitis Treatment is sphincteroplasty of the minor papilla

18 Cystic Fibrosis Occurs in 1:2500 live births Mutation in the CFTR gene, which codes for a protein expressed on the apical membrane of exocrine epithelial cells Reduced bicarbonate, lower ph, lower overall exocrine fluid volume Leads to pancreatic degeneration and fibrosis

19 Cystic Fibrosis Causes impaired absorption fats, proteins, fat-soluble vitamins Treatment: pancrelipase with meals

20 Pancreatitis Inflammation of the pancreas Can be acute or chronic, varying in severity from mild abdominal pain to necrosis and death

21 Acute Pancreatitis Pathophysiology Inappropriate activation of pancreatic enzymes leading to autodigestion Exact mechanism unknown Tissue damage mediated by elastase, phospholipase, and oxygen free radicals

22 Acute Pancreatitis Causes Include trauma, biliary tract stone disease, choledochal cysts, ductal developmental anomalies, drugs, metabolic abnormalities, and infection Often the cause is not apparent (idiopathic)

23 Acute Pancreatitis Biliary tract stone disease Rare in children; associated with hemolysis, liver disease, malformations, or infection Asymptomatic- treat conservatively Symptomatic- stone extraction +/- sphincterotomy via ERCP

24 Acute Pancreatitis Choledochal cysts Often associated with an abnormal pancreaticobiliary junction Higher risk of stones, malignancy, pancreatitis Cause pancreatitis via duct compression or bile reflux

25 Acute Pancreatitis ERCP of child with abnormally long common channel and a common duct stone

26 Acute Pancreatitis Presentation Sudden onset of midepigastric pain associated with back pain, severe vomiting, and low-grade fever Exam: distention, peritoneal signs, decreased bowel sounds

27 Grey-Turner sign Acute Pancreatitis

28 Cullen s sign Acute Pancreatitis

29 Acute Pancreatitis Laboratory Elevated serum amylase, urine amylase Normal serum amylase does not exclude the diagnosis (U amy /Serum amy ) x (Serum Cr /Urine Cr ) 0.03 => pancreatitis

30 Acute Pancreatitis Imaging May see sentinel loop of small bowel or colon cutoff sign Always get CXR- r/o pleural effusion, pulmonary oedema

31 Acute Pancreatitis Imaging CT pancreatography useful in delineating fluid collections and pancreatic necrosis ERCP useful in limited context MRCP- study of choice in children with unexplained or recurrent pancreatitis

32 Acute Pancreatitis Treatment Aggressive fluid resuscitation with careful monitoring of urine output Bowel rest with NG suction H 2 blockade (decrease secretin release) Moderate-severe cases may benefit from somatostatin analogue administration

33 Acute Pancreatitis Treatment Demerol for analgesia (avoid morphine) Hyperalimentation while patient is NPO Generally, resume PO after abdominal pain resolved and enzymes normalized

34 Acute Pancreatitis Surgical intervention Generally not indicated Main indications: severe necrotizing pancreatitis needing debridement or patients with pancreatic abscess Pancreatitis discovered incidentally at exploratory laparotomy: palpate gallbladder

35 Acute Pancreatitis Complications Pancreatic abscess- infection of necrotic pancreatic tissue or infected peripancreatic fluid Diagnosis established by Gram stain and culture of suspected abscess Treatment: debridement of necrotic tissue and placement of drains

36 Acute Pancreatitis Complications Pancreatic pseudocyst- peripancreatic fluid contained by a wall composed of fibroblastic reaction and inflammation, not epithelial-lined Acute vs. chronic- half of acute pseudocysts will resolve without intervention

37 Acute Pancreatitis Complications Pseudocyst size: < 5cm generally resolve without intervention Somatostatin may offer benefit Surgical treatment: internal vs. external drainage or excision Hemorrhage, rupture and infection possible complications

38 Acute Pancreatitis Complications Ascites- free fluid from the uncontained leakage of the main pancreatic duct Treatment: bowel rest, ERCP or MRCP to determine site of duct injury Distal injury: distal resection Proximal injury: Roux-en-Y jejunal onlay anastomosis

39 Acute Pancreatitis Complications Pancreatic fistula Most low-output fistulae close spontaneously Roux-en-Y jejunostomy to fistula leak point recommended in fistulae that fail to close

40 Chronic Pancreatitis Distinguished from acute pancreatitis by the irreversibility of the changes associated with inflammation Two types: calcifying and obstructive

41 Chronic Pancreatitis Calcifying type Most commonly caused by hereditary pancreatitis More common in children than obstructive type Associated with intraductal pancreatic stones, pseudocysts and more significant damage

42 Chronic Pancreatitis Hereditary pancreatitis Mutation in trypsinogen (PRSS1) gene on chromosome 7q35 Hypothesized that mutation leads to altered trypsin recognition site which prevents deactivation of trypsin within the pancreas

43 Chronic Pancreatitis Hereditary pancreatitis Presentation: recurrent attacks, beginning around 10yo, with progressing pancreatic insufficiency Patients have a 40% lifetime risk of pancreatic adenocarcinoma Tx: local excision, subtotal pancreatectomy, Puestow procedure, or sphincteroplasty

44 Chronic Pancreatitis Obstructive pancreatitis In children, due to choledochal cyst or pancreas divisum Treated by relief of the obstructionsphincterotomy/sphincteroplasty or stenting Results often disappointing

45 PHHI Persistent hyperinsulinemic hypoglycemia of infancy Gene mutations resulting in loss of normal feedback regulation of insulin release Two types: focal and diffuse

46 PHHI Focal type Localized tumor-like aggregation of islet cells Loss of maternal allele of chromosome 11p15 About 1/3 rd of cases of PHHI

47 PHHI Diffuse type Recessively inherited Presents as diffuse β-cell functional abnormality

48 PHHI Presentation/diagnosis Hypoglycemia shortly after birth (jitteriness, seizures) Measure serum glucose and insulin levels simultaneously (absolute insulin may be normal, but ratio to serum glucose will be abnormal)

49 PHHI Treatment Frequent feeding with IV glucose as needed Diazoxide or long-acting somatostatin analogue to inhibit secretion Glucocorticoids to promote insulin resistance Streptozosin- β-cell specific toxin

50 PHHI Treatment Surgery indicated after medical failure Diffuse type requires 90-95% pancreatectomy 75% rate of developing diabetes mellitus in later years

51 PHHI Treatment Focal type can be treated with more localized resection Long term prognosis depends on age at diagnosis and minimization of early neurologic damage due to hypoglycemia

52 Pancreatic Endocrine Tumors Insulinomas, gastrinomas and VIPomas are known to occur in children

53 Insulinoma Most common pancreatic endocrine tumor in children Presents with classic symptoms of hypoglycemia: dizziness, headaches, sweating and seizures Whipple s triad

54 Insulinoma Patients typically > 4yo 90% of cases are benign Usually solitary, exception is with MEN1 syndrome

55 Insulinoma Diagnosis Insulin to glucose ratio of > 1.0 (normal < 0.3) Always measure C peptide levels Benign vs. Malignant indicated by size (<2cm generally benign) and presence of metastases

56 Insulinoma Treatment All patients should undergo surgical resection Localize with CT pancreatography, endoscopic ultrasound Usually amenable to enucleation Malignant: need chemo (Streptozotocin)

57 Gastrinoma Pancreas is primary fetal source of gastrin Z-E syndrome: hypergastrinemia with PUD and a gastrin-producing tumor, typically located in the pancreas 65% gastrinomas are malignant

58 Gastrinoma Diagnosis Gastrin levels > 500 pg/ml Secretin stimulation test: administer 2U/kg IV secretin; postitive is 200pg/mL rise in serum gastrin

59 Gastrinoma Treatment Medically treat with omeprazole All patients with potentially resectable disease should be explored Only curative option is complete resection

60 Pancreatic Exocrine Tumors Generally rare Acinar cell adenocarcinoma more common than ductal adenocarcinoma (most common type in adults) Less aggressive, better prognosis Treatment: complete surgical resection

61 References Ashcraft, Keith, et al. Pediatric Surgery. 4th ed. Philadelphia: Elsevier-Saunders, Print. Lehman GA, Sherman SSO. Pancreas divisum. Diagnosis, clinical significance, and management alternatives. Gastrointest Endosc Clin N Am. 1995;5(1):145. DiMagno MJ, DiMagno EP. Chronic pancreatitis. Curr Opin Gastroenterol. 2005;21(5):544. Meissner T, Mayatepek E. Clinical and genetic heterogeneity in congenital hyperinsulinism. Eur J Pediatr. 2002;161(1):6. Talukdar R, Swaroop Vege S. Early management of severe acute pancreatitis. Curr Gastroenterol Rep Apr;13(2): Keim V, Bauer N, Teich N, Simon P, Lerch MM, Mössner J. Clinical characterization of patients with hereditary pancreatitis and mutations in the cationic trypsinogen gene. Am J Med. 2001;111(8):622.

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