PEDIATRIC PANCREAS

[AC. INFLAM. OF ABDOMINAL TIGER]

BackgroundPancreatitis (P) is uncommon in children: significant MM• 13/100k/y children (US). Adult incidence has increased

dramatically past 15y: changing trends in etiology, increased referral, better Dx

Due to underreporting & underDx incidence in children (& adults) is unknown

• Evaluate all abdo. pain with HI of suspicion• P. starts with blockage of ducts & acinar damage

activation of enzymes autodigestion (inflam., hge., necrosis, pseudocyst (23% of AP; >50% a/with traumatic P.)

MM. morbidity-mortality, hge. Hemorrhage, Dx. Diagnosis. HI. High index

Anatomy• P. is 6in long & sits across back of abdo, behind stomach;

p. duct joins CBD at ampulla of Vater• Has indistinct head, body, & tail. Abdo. aorta & IVC cushion

it from vertebrae. Crushing/blunt trauma can injure it

• Numerous cong. anomalies are seenPancreas divisum occurs in 5-15% popn.: unsuccessful

fusion of ventral & dorsal buds: accessory Santorini duct drains majority of p.: smaller, inadequate

drainage may cause chr. pain & rec. P.

Development

P. divisum with minor papilla stenosis causing rec. P. Note bulbous shape of duct adjacent to cannula (santorinicele).

Dorsal duct outflow obs. is the probable c/of P.

P. is retroperitoneal, except just a part of tail coming through mesenteric folds. Head is to Rt of L2, body over L1, & tail to Lt of T12

Blood supply of Pancreas

Normal histology

50% asymptomatic till adulthood. A/with: GI problems, Down, polyhydramnios. More risk for p./biliary Ca. CF: due obs. NB may have complete obs.: not feeding; spits, cries. Adult: fullness after meal, NV.

Dx: USG, AXR, CT, Upper GI & small gut series. Rx. mostly surgery. Complications. Jaundice, Ca, P. PUD, Perforation, peritonitis

Double Bubble Sign: dilated stomach &

proximal duo- in NB, typical in d. atresia, midgut

volvulus or annular p.

Annular pancreas A: Upper GI series, oblique v.: narrowing of duo- C-loop (arrows)B: ERCP: small ducts (arrows) encircling d., consistent with annular p.

Ectopic p.: lacks anatomic continuity with main p.; usually in stomach, duo-, jejunum, Meckel’s. Most are small & asymptomatic.

Incidence at laparotomy is 0.2%. Some develop pseudocyst, insulinoma, Ca. SS: abdo. pain, bleeding, obs.

Meckel’s

E.P.

Functions of the PExocrine Function• Lipase, amylase, trypsin & chymotrypsin, elastase,

kallikrein, phospholipase. Food in stomach: p. juice is released into duodenum

Endocrine …• Thousands of islets of Langerhans: (5% wt): 4 cell types: in

order of abundance: – 1. beta (insulin and amylin)– 2. alpha (glucagon)– 3. delta (somatostatin) – 4. gamma (pancreatic polypeptide)

Pancreas Disorders• Pancreatitis• Diabetes type 1 (autoimmune) & type 2• CF: affects multiple systems• Tumors: different cells. The commonest is from p. duct &

is often advanced at Dx. Islet cell: benign/Ca (Gastrinomas, glucagonomas, insulinomas)

• Pseudocyst• Enlarged p: may mean nothing, or, it can be due to an

anatomic defect. But other c/of an enlarged p. may exist & require treatment

Ac. P: Requires 2:1. Suggestive abdo. pain: acute, esp. in epigastrium2. S. amylase and/or lipase activity x33. Compatible imaging

Rec. P.: 2 distinct episodes of AP. Interval with:• Resolution of pain (≥1mo). Normal s. enzymes

Chr. P.: 1 of:1. Abdo. pain of p. origin & imaging of p. damage2. Evidence of exocrine p. insufficiency & imaging findings3. ... endocrine ... & imaging …4. Surgical/biopsy: features compatible with CP

PANCREATITIS

AC. PANCREATITIS IN CHILDRENEtiology (30% idiopathic). Many are a/with a systemic

illness. Some affect multiple organs• Common: trauma (23%), dev. anomalies (15%),

multisystem d. (14%), drugs/toxins (12%):• Less common• Inf. (10%): MR, coxsackie B, EBV, CMV & HBV (primarily in organ

transplants); HIV, campylobacter, HAV, salmonella, mycoplasma. Ascaris is a recognized c/of AP

• Hereditary/metabolic (4%):• Biliary: rare

Most adult AP are c/by alcohol or g. stone

–Trauma: RTA, abuse, bicycle handlebars–Cong.: p. divisum, malunion/maljunction, sphincter

anomaly, CD cysts, FAP–Drugs/toxin: TPN, tetracycline, valproate,

immunosuppressants–Hereditary: 2nd commonest cong. P. following CF.

AD. 20% no P. (variable penetrance)–Metabolic: hyperTG, hyperCa–Multisystem: Hypotension, ischemia. SLE, HSP, IBD,

(rarely) Kawasaki, Reye's

FAP. Familial adenomatous polyposis. CD choledochal

Etiology …

(Adults)

(3rd commonest)

No alcohol AP in children

(Adults)

Pathophysiology • AP: Inciters are unclear: acinar injury disruption of

ducts. Enzymes are activated: autodigestion

• Inflam. May be local/diffuse: ac., chr., necrotic, hgeic.Interstitial edema. Severe P. necrosis, BV blockage hge., & SIRS with MOF. Secretions often are walled off by gr. tissue (pseudocyst; 10-23% in AP, 50% after traumatic P. Mainly in lesser sac behind stomach).

Stomach, small gut, etc. may form part of capsule

CP: Chr. inflam. cell infiltration & irreversible fibrosis lossof exocrine & endocrine functions seen when ≥90% cells are destroyed

MOF. Multiorgan failure

p. in CT : enlarged (blue arrow) with indistinct shaggy borders.Peripancreatic fluid (red a.) and extensive infiltration of surrounding

fat (black a.)

Modified Glasgow Criteria (severe P.)Score >/= 3 indicates severe pancreatitis

PaO2 <8kPa (60mmhg)Age >55yearsNeutrophils: WBC >15 x109/l Calcium <2mmol/lRenal F. : Urea >16 mmol/lEnzymes: AST/ALT >200 iu/L or LDH > 600 iu/LAlbumin <32g/l Sugar: Glucose >10mmol/L

(‘PANCREAS’)

Histologic features• AP: Focal fat necrosis interspersed with interstitial hge.• CP: fibrosis, acinar destruction, lymphocytic infiltration, &

duct obstruction

CFClassical AP in adults: midepigastric pain radiating to back

• Children: quite varied; mostly: abdo. pain (90%), F. (76%) NV (73%), tenderness (85%), guarding (68%),

jaundice (28%), distention (18%), SoB (10%), H&M (5%). Others: HR, pallor, low BP (10%), rebound tenderness, & less BS, diaphoresis, pulmo. Edema

These are nonspecific. Eating may exacerbate pain• An acutely ill child may lie on his side with hips

& knees flexed. Pain typically increases for 24- 48h. Clinical course is variable

Typical posture of AP

Age 0-2y 3-10 11-20 Total Cohort

Abdo. pain 42.9% 93.2% 93.4% 90%

Epigastric tenderness

57.1% 86.4% 87.2% 85%

N/vomiting 28.6% 69.5% 78.1% 73%

Age group with presenting complaints

Acute hemorrhagic pancreatitis

Rare in children• Life-threatening; MR ~50% (shock, SIRS with MOF, ARDS,

DIC, massive GI hge., & systemic or peritoneal inf.

• PE: a bluish discoloration of flanks (Grey Turner sign) or periumbilical region (Cullen) due to blood pooling in fascial planes

Others: pleural e., H&M, coma

Cullen’s and Grey Turner’s Signs in AP

63y M, no h/of alcohol abuse had ac., severe epig. pain. S. lipase was 1380U/l (22-51). US: g. stones. He needed ICU. PE: jaundice and distention with ecchymosis (periumbilical and flank). These are due to free enzymes causing fat necrosis and inflam. with retroperitoneal /abdo. hge. that diffuses from retroperitoneum to umbilicus via round lig. and to subcut. tissues of flanks. These, although nonsp., are a/with severe AP and high MR. CT confirmed necrotizing P. with several ac. peripancreatic fluid collections (Balthazar grade E). He died of MO failure

DxPediatric P. is a Dx challenge!• No single test! Mainly clinical.• CF, blood tests, imaging

• Dx needs 2 or more of:– Amylase & lipase

most common: levels rise; but, do not correlate with severity. Other d. can also raise; so nonsp.US & CT most common imaging; to look for inflam. & are preferred both for Dx & FUImportantly, P. can sometimes appear normal

• s. amylase peaks at 48h, may be normal in 10-15%Typically stay raised x4d. Amylase can rise in other abdo. d., but not typically as high as in AP

• S. lipase is more specific than amylase in AP, & typically, stay raised x8-14d

It can also rise in other d.; so, all lab. data are assessed in cl. setting

ImagingImaging may be normal in 20% children with AP

• US: ducts, stones, margins. Primary screening (no IR/ sedation): a focally/diffusely enlarged, hypoechoic, sonolucent, p.; dilated ducts; p. mass; peripancreatic fluid; abscess; pseudocyst. Sensitivity is 50-80%; specificity 90%

• ERCP is gold standard; also therapeutic (g. stones, stenting, sphinterectomy). Essential for p. & biliary anomalies Sens. & spec. 90-100%. Has substantial observer variability, & may confuse AP for CP

Imaging …

• MRCP: non-invasive alternative to ERCP; no Rx option, no IR: for g. stones, T, inf., inflam., ducts, c/of PSecretin can enhance image

• CT is both highly sensitive and specific, risk of IR. Findings: ductal/parenchymal calcifications, dilatation of main ducts, pseudocyst & p. atrophy contrast, it is better for CP, complications, trauma,

T. Often used to FU: an enlarged p.; ill-defined margins; peripancreatic fluid; pseudocysts

MRCP showing changes consistent with chronic pancreatitis.

Comparison of EUS of normal p. and EUS of CP.Endoscopic ultrasound showed agreement with ERCP,

the gold standard, in 75% of cases

Radiography• XR: nonsp. distended loop of small gut (sentinel loop), g.

stones, dilatation of t. colon (cutoff sign), ascites, peripancreatic gas bubbles, ileus, L basal pleural e., & blurring of L psoas margin

Histology• AP: necrosis & inflam., hge. If severe: large, blue-black

hgeic. foci among yellow-white chalky areas of fat necrosis• CP: parenchymal damage & fibrosis; acinar destruction,

lymphocytic infiltration, & p. duct obs. Ducts are dilated & obstructed with protein plugs

CP: destruction of acini replaced by extensive fibrosis & relative

sparing of islets; with calculi

AP: Hemorrhage, necrosis, fat necrosis, neutrophils

Colon Cut off signSentinel Loop Sign

Enzymatic Fat Necrosis

Other lab. tests:

• Coagulopathies, leukocytosis, hypoCa, hyperglycemia, bilirubin & GGT, Hct. & CRP (prognosis)

• Urinary trypsin activator peptide (TAP) may show severity

• A high s. lipase (>19 above upper normal) & a low albumin & TLC have more morbidity. These 3 identify most at risk of severe P. & can direct a more aggressive Rx

• Sweat chloride: in CF• Genetic testing: for CF

No single drug. Mainly supportive. Admission may be neededUncomplicated AP usually resolve within 2-4dSevere AP occur in 20% AP in children: more MM, longer

stay, aggressive Rx. Mn. children are more likely to have comorbidities (CP & encephalopathy). Mn. can mask typical early CF

Goal: to achieve FEB, analgesia, p. rest, meta. homeostasis• Intractable V or ileus: NG suction for intestinal-pancreatic

rest (gastric contents in duodenum are the most potent activator of p. enzymes). FEB

• ABT in inf., severe P.:• Rx of complications

Management

• Analgesics: Tramadol is a central analgesic. Meperidine is opioid (severe pain): risk of ampullary spasm

• AB: Imipenem & cilastatin in combinationCeftriaxone has BS G-ve activity; lower efficacy against G+ve; & higher against resistant MO

• Chr. relapsing P.: enzyme supplement, insulin, & elemental or low-fat diets are useful

Nutrition• Intractable V/ileus: bowel rest. Stomach content in duo- is

the most potent activator of p. enzymes• Mild AP– If pt. feels hungry; can start eating in a day or 2 if no NV,

& symptoms have resolved (amylase now normal)– feeding small & slowly increasing low-fat, low-protein

soft diet appears safe, more calories; no transition• Severe AP– Severe P.: NPO & parenteral nutrition (avoid catabolism)– Parenteral nutrition should be avoided, unless enteral

route is N/A, not tolerated, or not meeting calories

RATIONALE OF EARLY ENTERAL NUTRITION

• The need to place p. at rest until complete resolution of AP no longer seem imperative– Bowel rest is a/with intestinal mucosal atrophy &

bacterial translocation: more inf. &complications

• Early enteral feeding maintains gut mucosal barrier, prevents disruption, & prevents translocation of bacteria that seed p. necrosis: less inf.

complications, organ failure & mortality

Route of enteral Nutrition

• Traditionally nasojejunal route has been preferred to avoid the gastric phase of stimulation BUT– Nasogastric route appears comparable in efficacy &

safety

MERITS OF NG ROUTE DEMERITS OF NG ROUTE

NGT placement is far easier than NJ tube placement (requiring

interventional radiology or endoscopy: expensive)

Slight increased risk of aspiration(overcome by placing pt upright &

be placed on aspiration precautions)

Surgery• Generally, surgery is not needed in children; mostly done in

intractable pain in chr./relapsing P. (failed Rx, Mn., & narcotic addiction), diffuse necrosis, hge., cong.

defects (p. divisum), ductal fistulae & AP induced ascites, abscess, pseudocyst

• Goal: to alleviate pain & preserve functions: – Distal pancreatectomy with Roux-en-Y pancreaticojejunostomy

(Duval procedure)– Lateral pancreaticojejunostomy (Puestow procedure)– Decompression of p. ducts, repair of p. divisum, sphincteroplasty

• A few cases benefitted with total pancreatectomy & ICT

ICT: islet cell transplantation

Pseudocysts• CF: ANV from obs. of stomach/gut, F (inf). Rarely, hge. into

abdo./gut. Pain, tender epigas. mass or abdo. fullness. Jaundice, chest pain, wt. loss, ascites. Post-traumatic: 60% need surgery. If size is

<5cm: observe x4-6w as most resolve>5cm: supportive x4-6w (cyst wall to mature) surgery>10cm has risk for rupture

Chr. pseudocysts (>3mo): best Rx by internal drainage– Cystogastrostomy: if adherent to back of stomach– Cystoduodenostomy: if present in the head of p.– Distal pancreatectomy: when it is in tail of p.– Cystojejunostomy: other than above– Endoscopic Rx has a success rate 85%

A Large Pseudocyst Compressing The

Duodenum

Contrast CT: upper abdomen: a well-defined p. pseudocyst

CT: a large well-marginated pancreatic pseudocyst

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• Total pancreatectomy with ICT is being evaluated for CP. ICT has no v. serious SE ("brittle diabetes,") (pt’s BGL often swings quickly from high ~ low ~ high

CP need multispecialty care (gastroenterologists, surgeons, nutritionists, psychologists, etc)

How long will AP last?• Usually a week• S/he needs not stay for that whole period. SS do improve

over time. A few have more severe d. & may end up admitted for a month or more

Complications of APImmediate common• Hypovolemic/septic shock a/with dysfunction of MOs• Renal dysfunction• Ascites, pleural e, ARDS, hypoCa, hge

Late common• P. necrosis• Infection• Pseudocysts (homogeneous collection of amylase-rich p.

fluid that lacks an epithelium). 10-20% of AP

LOCAL COMPLICATIONS (Ps)• Peripancreatic fluid collections• (Peri)Pancreatic necrosis (sterile ± infected)• Pancreatic abscess (Phlegmon)• Pseudocyst• Pancreatic ascites• Pseudoaneurysm• Adjacent organs: bleed, thrombosis, obs. jaundice,

bowel infarction, fistula, mechanical obs.

CP: Complications: pseudocyst, pseudoaneurysm, splenic vein thrombosis, CBD obs, duodenal obs, p. fistula, adenoCa

SYSTEMIC COMPLICATIONS• CVS– Shock: hypovolemic & septic– Arrhythmias/pericardial e./sudden death– ST-T nonspecific changes

• Pulmonary– Respiratory failure, pn., atelectasis, pleural e., ARDS

• Renal– Oliguria, azotemia, renal artery/vein thrombosis

• Hematological– Hemoconcentation, DIC

SYSTEMIC COMPLICATIONS …• Metabolic: HypoCa, hyperglycemia, hyperlipidemia,

hypermetabolic state• GIT: PU/Erosive gastritis, ileus, portal -/splenic vein

thrombosis with varices• Neurological– Visual (Sudden blindness: Purtscher’s retinopathy)– Confusion, irritability, psychosis, fat emboli– Alcohol withdrawal syn., encephalopathy

• Misc.: subcut. fat necrosis, Intra-abdominal saponification, Arthralgia

Typical fundus in Purtscher retinopathy: multiple cotton-wool spots surround disc after blunt thoracic trauma

Subcutaneous Fat necrosis in AP (nodules of panniculitis)

Pancreatic fat necrosis with ghost cells

Fat embolism: Fat can enter blood from BM due to trauma, & if fat is released by enzymatic digestion (AP). Common causes: 1. Fractures of long bones &/or operative manipulation of fractures; 2. trauma to fat or fatty liver; 3. AP. Fat emboli tend to be small and often cause small

infarcts adjacent to capillaries at the sites of blockage

Prognosis usually in children is excellent

Death is quite rare. But can happen. 1% in mild AP• 20-50% in severe AP. More with underlying d. 1/3rd die in

1w (MOF); 2/3rd later (MOF & sepsis)

Recurrence• Yes, it can occur in 10%. Even fewer will have multiple.

Another episode warrants additional testing to search for known c/of recurrent AP

Prevention• Some treatable c/of AP: gallstone d, hyperCa, high TG, &

abnormalities of ducts

CHR. PANCREATITIS IN CHILDREN

SS• Frequent or chr. Abdo. Pain is the most common; can be

constant or come & go unpredictably• Others: NV, wt. loss, D (oily motions). Some have trouble

digesting & may have poor growth, especially if quite young at first episode of P

• DM generally takes many years to appear, but this, too, is highly variable; some will DM in adolescence

Etiology of Chr. P in childrenSome are life-long, not often Dx until adulthood • Fibrosing P./TCP commonest in tropics• CF• Chr. Hereditary P. (usually Dx at adulthood)– Hyperlipidemias– Partial lipodystrophy– Wilson's disease– hemochromatosis– Alpha-1 antitrypsin deficiency

• IEM: (esp. branched chain aminoacidemias)• Idiopathic

CP: Dx

• As biopsy is impractical & potentially risky in many pts., clinical, lab., & radiologic criteria are essential for Dx.

• Lab. Direct: small gut intubation, using secretin, CCK or nutrient stimulants to measure secretion: highly

sensitive and specific, but time-consuming and invasive• Lab. Indirect: stool fat globules & assays for faecal

elastase, as well as other stool, breath, & urine/plasma tests. They tend to lack sensitivity & specificity & cannot DD between mild and moderate exocrine dysfunction. Faecal elastase & a 72h faecal fat is adequate

AXR in a 47y F with CP: diffuse p. calcification

CP: ManagementGoals: 1. Dx and etiology2. Analgesia3. Long-term FU to monitor & Rx exocrine insufficiency, DM4. No smoking and alcohol (risk of p. adenoCa)Others: antioxidants, enzyme, octreotide, pancreatic protease

inhibitors. But, currently insufficient evidence to recommend these

• Surgery is only indicated when there is chr., unremitting pain unresponsive to medical Rx. Goal: adequate drainage of p. ducts. This can be endoscopic or surgical. Pancreatic resections have high MM & rarely required

DD: Ac. vs. Chr. PancreatitisTrait Ac. P Chr. P

Duration 2w Life long

Emergency May be life threatening; an emergency (hge, shock)

Slowly developing

Etiologies Trauma (23%), dev. anomalies (15%), sys. d.

(14%), drugs/toxins (12%), viral (10%), etc. 25% is

unknown

Trauma, sys. d., cong. anomalies

Pathogenesis Morphological changes are reversible with good support

Calcifications and destruction of architecture

Complications Permanent DM almost never follows a single attack

DM , malabsorption

Lab High s amylase, lipase within 1-2d

Requires proof of irreversible damage to P, loss of digestive

F or DM: by CT/MRI, ERCP, endoscopic US

Peculiarities Of Pancreas

• Mixed gland• Develops from 2 primordial buds• Congenital anomalies can cause malignancy• Minimally infected• Disorders causes autodigestion• Chronic pancreatitis is life-long

MCQ

• HyperCa is common in AP• Imaging may be normal in AP• Lipase is more specific than amylase• DM is more common in AP• 25% AP are idiopathic

• Inf. is a common c/of AP in children• ERCP is a common cause of AP• Most p. pseudocysts require drainage• Gall stone pancreatitis is common in children• An enlarged pancreas is always significant

MCQ

THANK YOU……….