opening of the common bile duct to the same side as the

dorsal bud so that the duct lies ventral to and below the
opening of its duct.
The tip of the right ventral bud lobule eventually rests behind
the superior mesenteric artery. During the seventh week of
gestation, the smaller ventral bud fuses with the proximal part
of the dorsal pancreas.
Secretory acini appear during the third month as clusters of
cells around the ends of the ducts from which they are derived.6
Pancreatic development involves a process in which two
morphologically distinct tissue types must derive from one
simple epithelium. These two tissue types, exocrine (including
acinar cells, centro-acinar cells, and ducts) and endocrine cells,
serve disparate functions and have entirely different
morphology. In addition, the endocrine tissue must become
disconnected from the epithelial lining during its
development.7,8

PANCREATIC ANOMALIES
Pancreatic anomalies are numerous and are listed in Table 109-
1.

ANNULAR PANCREAS
The Pancreas During the sixth week of gestation, the common duct and the
right ventral bud lobule are carried in a dorsal direction around
N. Scott Adzick the circumference of the duodenum. The longer duct of the
dorsal pancreas anastomoses with that of the ventral pancreas to
establish the main pancreatic duct. Developmental errors at this
stage are believed to cause annular pancreas. This anomaly
occurs in 1 in 20,000 births and is more frequent in males than
Embryology females with a ratio of 2:1. The appearance of an annular
pancreas in a woman and her child,9 in siblings, and in members
------------------------------------------------------------------------------------------------------------------------------------------------

of two successive generations10 suggests a possible hereditary

The pancreas originates from two endodermal buds that link, but this has yet to be delineated. Annular pancreas can
arise from the caudal part of the foregut. One is the ventral cause duodenal stenosis or obstructive symptoms in the first
bud, which arises from the base of the hepatic diverticulum days of life.11
and is closely related to the bile duct; the other arises from
the dorsal surface of the duodenum immediately opposite PANCREAS DIVISUM
and in a slightly rostral direction to the liver diverticulum.
Both fuse at approximately the sixth or seventh week of The adult pancreas is derived from ventral and dorsal pancreatic
gestation. The dorsal bud appears before the ventral bud, buds that fuse by the end of the eighth week of gestation. Most
grows faster, and becomes larger.1,2 An axial duct is formed of the gland is derived from the dorsal bud and includes the
and opens into the gut tube by the beginning of the sixth superior anterior part of the head, body, and tail; it is drained by
week of gestation, and short branches appear soon the duct of Santorini through the minor papilla. The ventral bud
thereafter.3 becomes the posterior and inferior part of the head. The ventral
The ventral bud of the pancreas transiently consists of pancreatic bud is drained by the duct of Wirsung into the major
two lobules4; small ducts form within these lobules and papilla of Vater. With fusion of the ventral and dorsal pancreas
open into the hepatic diverticulum close to the gallbladder. and their duct system, the duct of Wirsung becomes the major
The ventral bud is carried away from the duodenum by duct, and the duct of Santorini usually regresses with the minor
elongation of the proximal part of the hepatic diverticulum papilla in approximately 90% of people. Failure of the two
from which it arises. This proximal part is called the ductal systems to unite results in the anatomic variant known as
common bile duct. The left ventral bud lobule later pancreas divisum. In this disorder the duct of Wirsung is small,
regresses completely. Because of rapid growth of the and the duct of Santorini becomes the major ductal system and
duodenum, which is limited to the left half of its maintains communication with the duodenum through the
circumference,5 the right ventral bud and the developing minor papilla. This configuration is found in 4% to 11% of
common bile duct rotate backward and become situated cadavers and in 3.25% of patients undergoing endoscopic
close to the posterior and inferior surface of the dorsal retrograde cholangiopancreatography (ERCP).
pancreatic bud. The outcome of this rotation is to bring the
1372 PART VII ABDOMEN

CONGENITAL SHORT PANCREAS may be completely covered by the pancreas (30%), (3) the
posterior surface of the bile duct may be uncovered (17%), and
Congenital shortening of the pancreas is an unusual anomaly
(4) the bile duct may be covered by two tongues of the pancreas
that has been described in individuals with polysplenia
(9%).16 Surgeons must be aware of these variants during surgery
syndrome,12 as well as being an isolated anomaly.13 It has also
involving the head of the pancreas.
1371 Pancreatitis
------------------------------------------------------------------------------------------------------------------------------------------------

Errors in Pancreatic Development Although pancreatitis is uncommon during childhood, it

Aplasia and hypoplasia must be considered in every child with unexplained acute or
Hyperplasia and hypertrophy recurrent abdominal pain. The prognosis in children is
Dysplasia generally good, with the exception of pancreatitis occurring
Ductal anomalies with multiorgan failure. Regardless of the cause, certain
Pancreas divisum common features are found in all types of pancreatitis.
Annular pancreas Patient management must be highly individualized because
Rotational anomalies numerous disease entities can cause pancreatitis.
Heterotopic pancreas
Cysts
Arterial, vascular, and lymphatic anomalies
ACUTE PANCREATITIS
Neoplasm Clinically, acute pancreatitis is defined as a single episode
Cystic fibrosis or recurrent episodes of abdominal pain associated with
elevated serum pancreatic enzyme levels. The morphologic
been seen in conjoined twins with a shared duodenum. In this correlate is acute focal or diffuse swelling and inflammation
condition the pancreas appears blunted and lacks tissue in the of the pancreas. Resolution of symptoms and normalization
region of the body and tail, which is believed to be caused by of blood biochemistry and anatomic abnormalities follow
agenesis of the dorsal pancreatic bud. Pancreatic function an acute episode. A continuum exists between acute and
generally remains normal despite partial absence of the chronic pancreatitis;as a result, recurrent episodes of acute
pancreatic parenchyma.14 pancreatitis may evolve into the typical clinical and
morphologic features of chronic pancreatitis.

Etiology
Surgical Anatomy Although pancreatitis in adults is usually related to alcohol
------------------------------------------------------------------------------------------------------------------------------------------------
abuse or biliary tract disease, in children the causes are more
The pancreas is composed of a head, body, and tail, although diverse.17–19 Most cases of acute pancreatitis in children
these areas have no distinct anatomic borders. The head sits to result from systemic infection, trauma, choledocholithiasis,
the right on L2, the body covers L1, and the tail rises to T12 on anomalies of the pancreaticobiliary duct system, and drugs
the left. The abdominal aorta and vena cava provide some (Table 109-2). Less common causes include idiopathic
cushioning effect against the vertebrae; however, certain forces
(such as seat-belt and steering wheel injuries) can cause blunt Causes of Acute Pancreatitis in Children
trauma to the body of the pancreas.
The pancreas is retroperitoneal. Peritoneal reflections from
the transverse mesocolon, small intestinal mesentery, and the
splenorenal and phrenocolic ligaments are present and establish
mesenteric planes for the direct spread of extravasated
pancreatic enzymes.15 These anatomic relationships are
important for understanding the pathophysiology of the various
radiographic signs seen in patients with acute pancreatitis.
The splenic artery provides most of the blood supply to the
pancreas and lies along its superior border with the splenic vein.
It seems that the blood supply is generally greatest to the head
of the pancreas. The head of the pancreas shares its blood supply
with the duodenum through the gastroduodenal artery and
superior and inferior pancreaticoduodenal arteries, which may
complicate surgery on the head of the pancreas. Blood from the
pancreas drains in a posterior direction into the superior
mesenteric vein and splenic vein via small, delicate branches.
Several anomalies of the pancreatic (third) part of the
common bile duct have been noted: (1) The bile duct may be
partly covered by a tongue of pancreas (44%), (2) the bile duct

Systemic infection
Mumps
Rubella
Coxsackie B virus
Trauma
Blunt abdominal trauma
Iatrogenic (e.g., surgery, ERCP)
Anomalies of the pancreaticobiliary duct system
Pancreaticobiliary malunion
Pancreas divisum
Hypertensive sphincter of Oddi
Choledochal cyst
Choledocholithiasis
Drugs
Azathioprine
Tetracycline
L-Asparaginase
Immunosuppressants
Valproic acid
Metabolic abnormalities
Hypertriglyceridemia
Hypercalcemia
Cystic fibrosis
Liver transplantation
Miscellaneous
Idiopathic
ERCP, Endoscopic retrograde cholangiopancreatography.
disease, metabolic disorders, and miscellaneous conditions
such as familial pancreatitis and Crohn disease.
Six percent to 33% of cases of pancreatitis are related to
disorders of the biliary or pancreatic duct,20 with
choledochal cyst and cholelithiasis being the most common.
A choledochal cyst is often associated with malunion of the
pancreatic and biliary ducts (pancreaticobiliary malunion),
and a long common channel may form and permit reflux of
bile into the pancreatic duct.21 The common channel is seen
easily on ERCP; this channel is often dilated and contains
protein plugs or stones, which may cause obstructive
pancreatitis or jaundice.
Cholelithiasis in children is frequently associated with
various hemolytic disorders including spherocytosis,
alphathalassemia, and sickle cell disease. It may also be
caused by obesity and the use of total parenteral nutrition.22
The role of pancreatic duct anomalies such as pancreatic
divisum and stenosis of the ampulla of Vater has only
recently been appreciated.23–26 Pancreaticobiliary malunion
not associated with a choledochal cyst is drawing clinical
attention because it tends to be overlooked on
ultrasonography; most patients with the disorder have
recurrent abdominal pain as a result of pancreatitis. 24,26–28
Tagge and colleagues26 found ductal anomalies in 6 of 61
(10%) patients with pancreatitis. They noted that patients
with ductal abnormalities usually had recurrent episodes
and that relapsing or chronic pancreatitis was also
associated with ductal anomalies.
Severe abdominal trauma may cause immediate acute
symptoms.29 However, less severe trauma may result in a
delayed onset and subacute manifestation. Child abuse
should be considered in all children with acute pancreatitis
who have a vague history.19 Finally, trauma may also be
CHAPTER 109 THE PANCREAS 1373
iatrogenically induced during the course of abdominal
surgery or ERCP.30
Drugs cause 8% to 25% of the cases of pancreatitis.
Drugs that cause pancreatitis most frequently include
didanosine, azathioprine, mercaptopurine, L-asparaginase,
and valproic acid.20,31,32 Recently, liver transplantation has
been reported as a possible cause of acute pancreatitis. The
incidence of this complication and the mortality rate in
children were 1.9% and 43%, respectively.33 A strong
association between the development of acute pancreatitis
after liver transplantation and several risk factors such as
the diagnosis of fulminant hepatic failure, retransplantation,
extensive dissection at the time of liver transplantation, and
the use of infrarenal arterial grafts has been reported. 34
Certain variants of the trypsinogen gene and cystic
fibrosis transmembrane regulation (CFTR) gene may cause
acute recurrent pancreatitis. Many patients with the
diagnosis of idiopathic pancreatitis have compound
heterozygote genotypes in which both alleles of the CFTR
gene are abnormal, thus constituting a variant of cystic
fibrosis. There are also numerous reports of an association
between chronic pancreatitis and a number of CFTR
mutations both in patients with cystic fibrosis and in carriers
with a single mutation.35
In certain conditions, destruction of the pancreas begins
antenatally. Infants with Shwachman-Diamond syndrome,
an autosomal recessive disorder mapped to the centromeric
region of chromosome 7,36 have pancreatic insufficiency at
birth, generally with low serum trypsinogen levels,
indicative of nearly total exocrine pancreatic atrophy by
birth.
Diagnosis
The diagnosis of acute pancreatitis is based on the clinical
history, physical examination, laboratory test results, and
findings of diagnostic imaging investigations. Determination of
amylase isoenzymes has also been used to increase diagnostic
accuracy by identifying the tissue from which the amylase
originates. Serum lipase levels may also complement
pancreatitis testing and increase the yield of positive
diagnoses.37 A new scoring system for acute pancreatitis in
children has been proposed that has better sensitivity than the
Ranson and Glasgow scores.22 The parameters are age (<7
years), weight (<23 kg), admission white blood cell count
(>18,500), admission lactate dehydrogenase level (>2000), 48-
hour trough Ca2þ level (<8.3 mg/dL), 48-hour trough albumin
level (<2.6 g/dL), 48-hour fluid sequestration (>75 mL/kg/48
hr), and 48-hour rise in blood urea nitrogen (>5 mg/dL).
Plain radiographs of the chest and abdomen are obtained to
exclude intestinal perforation. Occasionally radiopaque
gallstones, a gas-filled right colon, or a distended loop of small
intestine (sentinel loop) may be seen. Left basal pleural effusion
is relatively common, and mottling of the lung fields is a sign of
systemic cytokine release. Radiographic studies enhanced by
water-soluble contrast of the upper gastrointestinal tract are
occasionally useful, particularly in cases of trauma when injury
to the duodenum or small intestine is suspected.
Ultrasonography (US) and computed tomography (CT) are
useful for detecting pancreatic abnormalities. Trauma-induced
1374 PART VII ABDOMEN
injuries to abdominal organs, particularly the pancreas, are
readily detected on CT.
ERCP is rarely indicated for acute pancreatitis, but it
eventually becomes essential in any child who has pancreatitis
with an unclear cause.23,26 This technique is useful in cases of
relapsing pancreatitis associated with pancreaticobiliary
malunion.21,24 ERCP is an invasive method that can aggravate
pancreatitis and is often not an option during the acute phase of
pancreatitis. Magnetic resonance cholangiopancreatography
(MRCP) is a noninvasive method of obtaining images of the
pancreaticobiliary tract. MRCP images the common bile duct in
more than 96% of patients and detects common bile duct stones
with a sensitivity of 71% to 100%, thus exceeding the sensitivity
of US (20% to 65%) and CT (45% to 85%). Visualization of the
smaller pancreatic duct is successful in more than 80% of
patients.37 Miyano and colleagues38 have previously evaluated
the efficacy of MRCP in pediatric patients with acute
pancreatitis. Patients were divided into two groups. Group 1
consisted of seven patients in whom choledochal cysts were
sonographically diagnosed, and group 2 consisted of nine
patients with no obvious cause of acute pancreatitis.
Pancreaticobiliary malunion was detected in six of seven in
group 1 and in one of nine in group 2. Pancreatic divisum was
detected in one patient in group 1 but could not be confirmed in
any of the group 2 patients. Dilatation of the main pancreatic
duct was detected in one in group 1 and in three in group 2.
These findings indicate that MRCP is a potentially useful
method for identifying and ruling out structural abnormalities of
the pancreaticobiliary tract in children.
Treatment
Treatment of acute pancreatitis has two primary goals: (1) to
minimize any causative factors and (2) to provide meticulous
supportive care including liberal use of analgesics,
administration of parenteral fluids, maintenance of nutrition,
prevention of infection, and inhibition of endocrine and
exocrine activity.
Parenteral analgesia with narcotics or nonsteroidal
antiinflammatory agents is generally required, even in mild
cases of pancreatitis, because the pain can be extreme. It is
traditional to administer meperidine rather than morphine
because the latter produces ampullary spasm. Although
nasogastric suction is usually initiated to reduce vomiting and
abdominal distention, the value of nasogastric decompression is
questionable, unless the patient is vomiting. Aspiration of
gastric acid may reduce pancreatic exocrine secretion by
limiting the release of secretin. Oral feeding must be withheld
to reduce pancreatic stimulation. Total parenteral nutrition
should be initiated early to avoid malnutrition. 39 In addition,
early placement of a central venous catheter in patients with
severe disease will provide access for aggressive intravascular
volume support and nutrition. The hematocrit and serum levels
of glucose and calcium should be measured, and hourly urine
output should be monitored carefully.
Although the advantages of prophylactic antibiotics have not
been proved, patients with necrotizing pancreatitis may
benefit.40 Other treatment strategies involving somatostatin,
glucagon, anticholinergics, histamine blockers, and protease
inhibitors have been recommended, but to date they have not
shown conclusive benefit.
Standard medical treatment must be used in patients with
acute pancreatitis in an attempt to control the disorder before
surgical intervention, which is rarely required in children but is
occasionally performed if the diagnosis is uncertain or a
complication develops after an acute episode such as a
pseudocyst or an abscess. Patients with acute pancreatitis
associated with underlying pancreaticobiliary disease generally
require surgical correction of the underlying condition before
cure can be expected.
In the management of severe acute pancreatitis, a major
decision is whether and when surgery for pancreatic necrosis or
infection is necessary. Infection of necrotic pancreatic tissue is
the major risk factor for mortality in severe acute pancreatitis
and is an indication for surgery. On the other hand, there is
support for nonsurgical conservative management of sterile
pancreatic necrosis including antibiotic treatment. The reported
death rate is 1.8% with sterile pancreatic necrosis and 24% with
infected necrosis.41 Early surgery has been associated with
increased mortality and should be delayed, if not avoided. 42
CHRONIC RELAPSING PANCREATITIS
Chronic relapsing pancreatitis is characterized by recurrent
episodes of upper abdominal pain associated with varying
degrees of pancreatic exocrine and endocrine dysfunction.
Relatively few case series of chronic relapsing pancreatitis in
childhood exist, although it is more frequently being suspected
in children with recurrent episodes of abdominal pain.43–45 The
disease produces a wide variation of progressive and
irreversible structural changes in the pancreas.44 At present, the
most controversial aspect of treatment of this disorder is the
choice of an appropriate surgical procedure.
Causes and Pathophysiology
In children the most common causes of chronic relapsing
pancreatitis are trauma, heredity, systemic disease, and
malformations of the pancreaticobiliary duct such as
pancreas divisum, annular pancreas, and
choledocholithiasis. In addition, various unusual conditions
including metabolic disease, endocrine disorders, and
inflammatory bowel disease13 may cause the disorder.
Causes of chronic relapsing pancreatitis are listed in Table
109-3.
Certain congenital anomalies affect the pancreas and
surrounding tissue, several of which are associated with
chronic relapsing pancreatitis. Obstruction of pancreatic
flow caused by a stenotic papilla of Vater and bile reflux
resulting from a common channel are believed to be
responsible for the resultant inflammation, which may be
reversible if the obstruction is relieved. A relatively
common cause of relapsing pancreatitis is pancreas
divisum,46 in which most of the pancreatic fluid flows
through the minor duct of Santorini, with the possibility of
a relative obstruction to flow because of anatomy and flow
dynamics. Some series have reported an increased incidence
of pancreas divisum in patients with idiopathic chronic
pancreatitis.46 Annular pancreas, which results from an error
of rotation or fixation of the embryologic pancreatic
primordium, has also been associated with chronic
pancreatitis (Fig. 109-1).63 Pancreaticobiliary malunion
 CHAPTER 109 THE PANCREAS 1375
with or without choledocholithiasis may likewise result in Congenital anomalies of the pancreatic duct
relapsing chronic Pancreaticobiliary malunion
pancreatitis.24,27 Pancreas divisum
Annular pancreas
In the past few years, several genes have been identified Biliary tract disorders
as being associated with hereditary and idiopathic chronic Choledocholithiasis
pancreatitis: PRSS1, CFTR, and SPINK1. SPINK1 Cholelithiasis
mutations were found predominantly in patients without a Trauma
family history. These mutations were most common in those Systemic infection
with idiopathic chronic pancreatitis, whereas patients with Hereditary pancreatitis
hereditary chronic pancreatitis predominantly had PRSS1 Hyperlipoproteinemia
mutations.47 Hyperparathyroidism and hypercalcemia
Cystic fibrosis
Inborn errors of metabolism
Chronic inflammatory conditions
Causes of Chronic Relapsing Pancreatitis in Children Crohn disease
Ulcerative colitis
Systemic lupus erythematosus
Chronic fibrosing pancreatitis
Juvenile tropical pancreatitis
Idiopathic chronic pancreatitis

FIGURE 109-1 Preoperative endoscopic retrograde

Diagnosis
The degree of permanent damage to the pancreas may be
assessed by blood tests (pancreatic enzymes), stool tests
(pancreatic enzymes, fecal fat), and noninvasive tests of
pancreatic function such as the pancreatic stimulation
(secretin) test. In 30% to 50% of adolescents and adults with
chronic pancreatitis, plain radiographs of the abdomen
reveal pancreatic calcification. Calcification is diagnostic of
chronic pancreatitis, even if clinical evidence of pancreatic
disease is absent. However, the incidence of calcification in
children with chronic relapsing pancreatitis is low, except
in younger children with hereditary pancreatitis, in whom
the incidence is high.
US is ideal for examining the pancreas in children.
Dilatation of the pancreatic or biliary tracts may be noted,
and calcification and complications such as pseudocysts,
abscesses, calculi, and ascites can be seen. CT is useful for
visualizing the size of the pancreas and its ducts (Fig. 109-
2) and for detecting small calculi that may be missed on
plain radiographs and US. ERCP is an important tool in the
diagnosis and management of chronic relapsing pancreatitis
in adults and children.23 Pancreaticobiliary malunion with
or without dilatation of the bile duct may be detected.24
ERCP is up to 90% accurate in diagnosing ductal
abnormalities. However, as described earlier, MRCP has
been greatly refined in the past decade. MRCP is considered
to be equivalent to ERCP for the diagnosis of many
pancreatic and biliary conditions and is preferable because
it is noninvasive and safer.38
Surgical Treatment
cholangiopancreatography in a patient with an annular pancreas. A
complex anomaly of the pancreatic duct with dilatation (arrowheads) and
stenosis (arrows) is shown. The patient underwent a longitudinal
pancreaticojejunostomy (Puestow) procedure.
FIGURE 109-2 Computed tomographic scan of a patient with an irregularly
dilated pancreatic duct (arrows). The patient underwent a longitudinal
pancreaticojejunostomy (Puestow) procedure.
Surgery for chronic relapsing pancreatitis is done to relieve
pain, treat complications, or both. Surgery on the pancreas
is generally of three types: (1) sphincteroplasty45; (2)
pancreatic drainage via longitudinal
pancreaticojejunostomy (Puestow),48 end-to-end
pancreaticojejunostomy (Duval),49 or the Frey
procedure50,51; or(3)partial ortotal pancreatectomy. Several
groups of investigators have attested to the success of
sphincteroplasty in controlling the symptoms of chronic
pancreatitis in carefully selected patients. Correct use of this
procedure, however, demands that intrapancreatic ductal
obstruction be ruled out by pancreatography. O’Neill and
colleagues45 reported good results in six of seven children
who underwent sphincteroplasty for chronic pancreatitis.
The general indication for the use of a direct ductal
decompression procedure is evidence of pancreatic ductal
ectasia with multiple intrapancreatic duct strictures. An
important secondary feature of drainage procedures is
preservation of existing endocrine function by avoiding major
pancreatic resection. Longitudinal pancreaticojejunostomy
(Puestow technique) in adults has been successful in eliminating
or ameliorating pain from chronic pancreatitis in 70% to 97% of
patients in series reported 3 decades ago.52,53 In children, several
authors have shown that either the Puestow procedure43,54–56 or
the Frey procedure51 improves pancreatic function, decreases
hospitalization, and increases body weight toward ideal. Others
have reported that distal pancreatectomy and
pancreaticojejunostomy are effective.57 Tailored
organpreserving resective pancreatectomy can also be
performed with low morbidity and mortality in pediatric
patients with chronic pancreatitis and not responding to medical
management. Total pancreatectomy is not generally indicated in
1376 PART VII ABDOMEN
58
children. The individual procedure for chronic pancreatitis
should be tailored to the pancreatic ductal anatomy.
PANCREAS DIVISUM
The embryology of this entity was described in the first section
of this chapter. Pancreas divisum is suspected on MRCP or
ERCP when the duct of Wirsung fails to be visualized after
injection of the major papilla or when it is attenuated and
rudimentary. MRCP is a useful and noninvasive diagnostic tool
for pancreas divisum (Fig. 109-3), but ERCP can provide
detailed information on the pancreatic duct. If pancreas divisum
is suspected after injection of the papilla of Vater, an attempt
should be made to find and cannulate the minor papilla, but this
is possible in less than half the cases because of its small size
and the angle at which it meets the duodenum. If the minor
papilla can be entered, ERCP will demonstrate that the duct
FIGURE 109-3 Magnetic resonance cholangiopancreatography in a patient with
recurrent pancreatitis. The duct of Santorini is the dominant duct, and it
extends the entire length of the body and tail of the pancreas (arrowheads).
of Santorini is the dominant duct and that it extends the entire
length of the body and tail of the pancreas. Imaging of the duct
of Santorini occasionally demonstrates dilatation, irregularity,
or stricture suggestive of chronic pancreatitis.
Autopsy studies have suggested that pancreas divisum,
which is found in 4% to 11% of patients, is the most common
congenital anomaly of the pancreas. When absence of the duct
of Wirsung is associated with pancreas divisum, approximately
10% of affected patients have anomalous anatomy resulting in
most or all of the pancreatic secretions draining by means of the
accessory papilla.59,60
Pancreas divisum should not be regarded as a disease.
However, if the orifice of the accessory papilla is stenotic,
pancreatitis can result. Stenosis of the minor papilla is probably
developmental because the orifice is usually small with no
evidence of inflammation. The incidence of pancreas divisum
may be significantly higher in patients with unexplained
recurrent pancreatitis, and it was detected in up to 25% of
patients. Neblett and O’Neill reported that pancreas divisum
was identified in 7.4% of all children with pancreatitis and
19.2% of children with relapsing or chronic pancreatitis. In 10
patients with pancreas divisum, 8 had complete pancreas
divisum and 2 had incomplete variants.61
The primary goal of treatment of pancreas divisum
associated with pancreatitis is to establish adequate drainage of
the duct of Santorini. The progression of disease to pancreatic
insufficiency can be arrested when the obstruction is relieved
early. Correction may not only preserve pancreatic function but
may also help ensure that normal growth and development
occur.
Several reports have shown that adequate drainage of the
duct of Santorini can be achieved with accessory papilla
sphincteroplasty.46,59–61 A report by Adzick and colleagues
delineated the technical details of the operative procedure. 46
Endoscopic sphincterotomy has been performed, but restenosis
and recurrence of symptoms have been reported. If chronic
pancreatitis has developed in the presence of a dilated duct,
longitudinal pancreaticojejunostomy should be considered.
Neblett and O’Neill61 reported that 8 of 10 patients with
pancreas divisum underwent surgery: 7 underwent
transduodenal sphincteroplasty of the accessory papilla, along
with sphincteroplasty of the major papilla in 2 (plus septoplasty
in 1). Three patients underwent longitudinal
pancreaticojejunostomy, as a primary procedure in one patient
with mid-ductal stenosis and in two because of recurring
pancreatitis after sphincteroplasty without endocrine and
exocrine pancreatic insufficiency. Surgical intervention is
directed toward relief of ductal obstruction and may involve
accessory duct sphincteroplasty alone or in conjunction with
major sphincteroplasty and septoplasty. Patients with more
distal ductal obstruction or ductal ectasia may benefit from
pancreaticojejunostomy. In an extremely rare case, Miyano and
colleagues treated a patient with coexistence of pancreas
divisum, choledochal cyst, and pancreaticobiliary malunion.
Figure 109-4 shows the preoperative ERCP and intraoperative
cholangiogram. This patient underwent complete excision of the
choledochal cyst with a Roux-en-Y hepaticojejunostomy,
followed by transduodenal papilloplasty to allow complete
drainage of the common channel.62
Cysts and Pseudocysts
------------------------------------------------------------------------------------------------------------------------------------------------
Pancreatic cysts are relatively unusual in children. The
causes of these cysts tend to be diverse and include both
congenital and acquired conditions. Pancreatic cysts can be
classified as congenital and developmental, retention,
enteric duplication, and pseudocysts.
CONGENITAL AND DEVELOPMENTAL FORMS
Congenital and developmental cysts of the pancreas are rare
and may be encountered in a fetus, infant, child, or adult.
Only 25 cases have been reported in the pediatric literature
to date.64–67 These cysts have a female preponderance. They
are most common in the body and tail of the pancreas, are
more often unilocular than multilocular, and are lined with
epithelium. The cysts are usually filled with a cloudy,
yellow sterile fluid that has no enzyme activity, and they are
remarkably free of adhesions and infection. They have been
reported to occur simultaneously in other organs; for
example, von Hippel-Lindau disease is characterized by
hereditary cerebellar cysts, retinal hemangiomas, and cysts
of the pancreas and other organs.68 The cysts that occur with
cystic fibrosis are not considered pancreatic pseudocysts
and are not discussed in this chapter.
Clinically, congenital and developmental cysts are
detected in the prenatal period as an incidental sonographic
finding or as a cause of polyhydramnios. After birth, they
may be manifested as asymptomatic abdominal distention,
as vomiting or jaundice caused by extrinsic pressure on
neighboring organs, or as an asymptomatic mass. Surgical
treatment consists of total excision of cysts located in the

pancreatic body or tail and either internal drainage or
complete resection of those in the pancreatic head.
RETENTION CYSTS
Retention cysts of the pancreas are rare and believed to
result from chronic obstruction of the gland. They contain
cloudy fluid composed of pancreatic exocrine secretions
and a high concentration of pancreatic enzymes. Such cysts
are lined with ductal epithelium unless it has been destroyed
by chronic dilatation or inflammation from enzyme
exposure.
FIGURE 109-4 A, Preoperative endoscopic retrograde cholangiopancreatography. B, Intraoperative cholangiogram in a patient with a choledochal cyst
associated with pancreas divisum. The septum (arrowheads) in the intrapancreatic bile duct is also seen.
ENTERIC DUPLICATIONS
Enteric duplication involving the pancreas is rare and
usually associated with gastric duplication.69 This
duplication is most likely to result from failure of regression
of an enteric diverticulum formed from the pancreatic duct.
Many of the reported cases of enteric duplication involving
the pancreas communicate with the pancreatic duct, are
lined with gastric-type epithelium, and contain ectopic
pancreatic tissue in their walls. Pancreatic duplication cysts
have been noted on fetal US.70
The most common symptom in these patients is recurrent
abdominal pain, often postprandial. Pancreatitis associated
with enteric duplication cysts is believed to be caused by
obstruction of the pancreatic ducts by viscous secretions
from the cyst or by blood and debris from peptic ulceration
within the cyst. In patients without pancreatitis, pain may be
caused by tension on the wall of the cyst as a result of
accumulation of secretions and muscular contraction. 71 CT
may help identify the location and size of duplication cysts,
as well as any edema of the pancreatic head. ERCP or
MRCP is useful to outline ductal anatomy and demonstrate
any communication between the duplication cyst and the
pancreatic duct to aid in planning the surgical approach. To
date, virtually all duplication cysts reported in the literature
have been treated by extirpation, and some have required
pancreaticoduodenectomy.69,72
PSEUDOCYSTS
Clinical Features
Pancreatic pseudocysts are localized collections of
pancreatic secretions that do not have an epithelial lining
and develop after pancreatic injury, inflammation, or duct
obstruction. The most common causes of pseudocysts in
children are trauma and infection.73 Drug-induced acute
pancreatitis such as with valproic acid is also a rare cause
of pancreatic pseudocyst.74 These cysts typically lie in the
lesser sac behind the stomach and are composed of a fibrous
capsule surrounded by inflamed connective tissue. The
capsule of the cyst may also be formed by neighboring
tissue such as the stomach, duodenum, colon, small
intestine, or omentum. Pseudocyst fluid is clear or straw
CHAPTER 109 THE PANCREAS 1377
colored in most cases and may contain toothpaste-like
debris. The amylase level of cyst fluid is typically higher
than 50,000 Somogyi U/mL.
Diagnosis
The presence of a pancreatic pseudocyst is suggested by a
history of blunt abdominal trauma; an illness resembling
pancreatitis, possibly followed by a symptom-free interval of
weeks to months; or palpation of a mass in the epigastrium or
left upper quadrant. Abdominal pain is the most common
symptom, with jaundice, chest pain, signs of gastric obstruction,
vomiting, gastrointestinal hemorrhage, weight loss, fever, and
ascites also being features.
US, CT, and magnetic resonance imaging (MRI) are helpful
and accurate in diagnosis. These studies are also invaluable for
evaluating the thickness of the cyst wall and for observing
changes in the cyst during the ensuing period of treatment (Fig.
109-5). ERCP is often useful because it can definitively
determine the status of the pancreatic duct and thus guide
surgical interventions.75,76 Rarely, pancreatic pseudocysts can
extend into the mediastinum in children.77
Treatment
Optimal management of a pancreatic pseudocyst remains
controversial. Treatment options range from conservative
medical management to surgical drainage.78 Conventional
management involves supportive therapy over a 6-week waiting
period, during which time either the cyst resolves spontaneously
or the cyst wall undergoes fibrous maturation, thereby
permitting internal surgical drainage to the stomach or jejunum.
This 6-week interval is what has traditionally been accepted, but
CT may demonstrate thickening of the cyst wall sufficient to
hold sutures as early as 3 to 4 weeks. Surgical drainage is
usually performed in adults when necessary but is controversial
in children because some pancreatic pseudocysts in this group
resolve without surgical intervention and have a low risk for
recurrence. Pseudocysts from nontraumatic etiologies are more
likely to require surgical intervention, whereas traumatic
pseudocysts are more amenable to nonoperative treatment. 79
Octreotide acetate, a long-acting analogue of somatostatin, may
facilitate medical management of pancreatic pseudocysts.80
A significant risk for complications such as infection or
major hemorrhage in untreated pseudocysts or persistence of
severe symptoms may be an indication for earlier intervention.
If the patient cannot withstand major surgery, external drainage
is preferred. There is significant evidence indicating that
internal drainage, especially transgastric cystogastrostomy or
Roux-en-Y cystojejunostomy, is effective in the treatment of
pancreatic pseudocyst. Roux-en-Y cystojejunostomy is the most
widely used internal drainage procedure for this problem and is
associated with the lowest rate of complications and
recurrence.81
In contrast to this approach, others82,83 have reported that
percutaneous drainage and endoscopic transmural drainage
are safe and efficient procedures. However, it is generally
1378 PART VII ABDOMEN
recognized that external drainage carries a higher risk for HI that result from mutations of glucokinase or glutamate
complications such as fistula formation and a higher dehydrogenase genes that are responsive to diazoxide
recurrence rate than internal drainage does. Internal treatment.
drainage procedures cannot be accomplished until the wall Neonates with HI may have either diffuse involvement
of the pseudocyst has matured. Recent studies have shown of the pancreatic beta-cells or focal adenomatous islet cell
that internal drainage should be performed in patients with hyperplasia. Mutations of the SUR1/Kir6.2 complex are
pseudocysts that are more than 6 weeks old and have a involved in both of these types. Recessive mutations cause
diameter larger than 5 cm because a large proportion of diffuse HI, whereas loss of heterozygosity together with
pseudocysts regress during the first 6 weeks after diagnosis inheritance of a paternal mutation causes focal adenomatous
and the risks associated with managing the pseudocyst are HI. Patients with diffuse disease have recessively inherited
reduced. Cystogastrostomy has been performed mutations of the SUR1/Kir6.2 complex, whereas patients
laparoscopically.84 with focal disease have normal beta cells, as well as a focal
Though less commonly used than drainage procedures clone of abnormal beta cells that are homozygous for the
into the stomach or jejunum, cystoduodenostomy is SUR1/Kir6.2 mutation. The focal lesions arise by a two-hit
effective when a cyst is closely adherent to the duodenum. loss-of-heterozygosity mechanism.87 First, there is a
Either pancreaticoduodenectomy or distal pancreatectomy, specific loss of maternal alleles of the imprinted
as indicated by anatomy, is effective in treating patients with chromosome region 11p15 in cells from the focal lesion but
pseudocysts under ideal circumstances. Distal pancreatic not in the surrounding normal pancreatic cells. Second,
resection is indicated in patients with a pseudocyst in the there is a transmission of a mutation of SUR1/Kir6.2 in the
body or tail of the pancreas, particularly if associated with paternal chromosome 11p; focal lesions have been linked to
multiple small cysts. Pseudocysts involving the head and non-Mendelian expression of paternally transmitted SUR1
uncinate process of the pancreas that are not amenable to mutation in which there is duplication and reduction to
internal drainage are rare and may require proximal homozygosity of the mutant paternal allele. In the future,
pancreatic resection, but such resection should be done only molecular biology testing of peripheral leukocytes may help
as a last resort. differentiate focal from diffuse disease. However, the
Hyperinsulinism search for mutations is currently of limited use in clinical
practice because the process takes many weeks and not all
------------------------------------------------------------------------------------------------------------------------------------------------

mutations are known.

Congenital hyperinsulinism (HI) is a rare derangement of One of the big challenges in diagnosis has been that the
glucose metabolism, which carries an estimated incidence diffuse and focal forms of HI are clinically identical.
of 1 to 1.4 in 50,000 live births, leading to about 80 to 120 Patients with either focal or diffuse disease are usually large
new cases in the United States each year. Higher rates of 1 for gestational age, reflecting the effects of HI on fetal
in 2500 live births have been reported in areas of high growth. We have found that approximately 55% of our
consanguinity such as the Arabian Peninsula. patients have focal disease, and about 45% have diffuse
Pancreatectomy for management of persistent infantile disease. Distinguishing focal from diffuse disease is of
hypoglycemia was first performed at the Children’s importance in guiding the extent of surgical resection.
Hospital of Philadelphia (CHOP) in 1950. Inappropriate Patients with diffuse disease often require near-total
oversecretion of insulin is the hallmark of HI. The old term pancreatectomy, which has the long-term risk of diabetes
“nesidioblastosis” should be discarded. HI is the most mellitus. Conversely, babies with focal disease can be cured
common cause of persistent hypoglycemia in neonates and with a selective partial pancreatectomy with little risk of
can lead to seizures and irreversible brain damage. 85 subsequent diabetes.
At the Congenital Hyperinsulinism Center at CHOP, we use
a multidisciplinary approach (pediatric endocrinology,
DIAGNOSTIC APPROACH radiology, pathology, and surgery) for patients with HI to
Genetics distinguish focal from diffuse disease, localize focal lesions,
treat focal disease with partial pancreatectomy, and treat
Molecular biologic studies have shown that abnormalities
medically refractory diffuse disease with near-total
of the KATP channel, which are encoded by the sulfonylurea
pancreatectomy. During the past 12 years, more than 250
receptor 1 (SUR1) and Kir6.2 genes, are responsible for
patients (median age 10 weeks) with HI have been treated with
altered control of insulin secretion.85 In response to elevated
pancreatectomy at CHOP. This section on hyperinsulinism will
glucose levels, the KATP channel closes, depolarizing the
be based largely on the clinical experience at CHOP. We have
beta-cell membrane and initiating calcium-dependent
also crafted an educational DVD regarding the management of
release of insulin from the beta-cell storage granules.
congenital hyperinsulinism that is available at the CHOP
Uncontrolled insulin secretion may occur if either the SUR1 website (www.chop.edu).
or Kir6.2 proteins are defective. The SUR1/Kir6.2 form of HI
may not be controlled with medical therapy such as Diagnosis and Medical Management by
diazoxide, which acts on SUR1 to suppress insulin secretion, Pediatric Endocrinology
and pancreatectomy is often necessary.86 In contrast,
surgery is not usually necessary in other genetic forms of

Babies with HI present with severe and persistent hypoglycemia
manifested by seizures, lethargy, apnea, and other symptoms
resulting from neuroglucopenia.85 The diagnosis of congenital
HI is established if fasting hypoglycemia (glucose < 50 mg/dL)
occurs simultaneously with an inappropriately elevated plasma
insulin (>2 mU/mL), low plasma beta-hydroxybutyrate (<2
mmol/L) and free fatty acids (<1.5 mmol/L), and an
inappropriate glycemic response to intravenous glucagon (>30
mg/dL rise in serum glucose level). Medical therapy to maintain
euglycemia is standardized and involves high continuous
intravenous infusions of glucose as measured by the Glucose
Infusion Rate (which is the amount of glucose infused in
mg/kg/min), frequent oral feedings, and administration of
diazoxide, glucagon, and octreotide. Early efforts to distinguish
focal from diffuse disease involved the injection of intravenous
calcium and tolbutamide (a sulfonylurea) to elicit different
types of insulin responses by focal and diffuse disease, but the
results were not predictive enough to be clinically useful.
Preoperative assessment of babies with HI reveals that they
are large, are often fluid overloaded due to high intravenous
glucose requirements, have hepatic enlargement due to
steatosis, may be anemic due to frequent blood sampling, and
have oral aversion. They are predisposed to central venous line
sepsis both preoperatively and postoperatively. Octreotide is the
mainstay of medical therapy for HI but can rarely lead to
necrotizing enterocolitis because octreotide reduces splanchnic
blood flow in a dose-dependent manner.88
Localization Procedures Performed by Radiology
Diagnostic radiology tests such as US (both preoperative and
intraoperative), MRI, CT, contrast angiography, and
radiolabeled octreotide scans have all been unsuccessful in
identifying focal lesions. For insulinoma localization in adults,
intraoperative saline injection into the pancreas followed by
tissue aspiration with rapid insulin measurements has been
helpful, but this localization technique is untenable in the fragile
neonatal pancreas.
Two interventional radiology tests have been used in an
attempt to differentiate focal from diffuse disease. The Arterial
Stimulation with Venous Sampling (ASVS) technique involves
selective pancreatic angiographic stimulation and venous
sampling using intra-arterial calcium, which stimulates
abnormal islet cells to release insulin. An immediate rise in
insulin from stimulation in only one artery suggests focal HI in
the corresponding area of the pancreas (gastroduodenal artery—
pancreatic head; superior mesenteric artery— uncinate process
and neck; splenic artery—pancreatic body or tail), whereas an
insulin rise in all three areas suggests diffuse HI. We and others
have also used transhepatic portal venous catheterization and
selective sampling of the pancreatic veins (THPVS). Both
techniques require that the patient be off all glycemic
medications (5 days for diazoxide, 1 to 2 days for octreotide)
before catheterization under general anesthesia. THPVS
requires that glucose levels be maintained at 50 mg/dL during
the procedure as compared with 60 to 80 mg/dL for ASVS. For
THPVS, the pancreatic venous insulin levels are compared with
simultaneously drawn plasma levels of insulin and glucose.
Both ASVS and THPVS are technically demanding and have
CHAPTER 109 THE PANCREAS 1379
limited specificity and sensitivity for distinguishing between
focal and diffuse disease. These techniques are being replaced
by a new PET-CT scan technique using 18-Fluoro-L-DOPA.
Neuroendocrine cells have an affinity for taking up and
decarboxylating amino acid precursors such as L-
dihydroxyphenylalanine ( L-DOPA). Decarboxylation of the L-
DOPA to dopamine in islet cells allows meaningful localization
by means of PET scanning, using the radioactive isomer
18Fluoro-L-DOPA. The isotope is manufactured by the
Cyclotron Facility at the University of Pennsylvania on the day
of the PET scan because of the isotope’s short half-life, and it is
administered to patients under an Investigational New Drug
(IND) program approved by the U.S. Food and Drug
Administration. Hopefully, 18-Fluoro-L-DOPA will become
commercially available in the future so that it can be used in
other medical centers. The PET results are dramatic and visually
spectacular for preoperative localization of a focal lesion (Fig.
109-6).89 In more than 140 PET scans for HI, we have found that
PET-CT scans read as showing a focal lesion have been 100%
accurate in localizing a lesion. However, in about 20% of
PETscans that were interpreted as showing diffuse disease, the
patient at operative exploration will prove to have a focal lesion
that was usually small. This false-negative rate should decrease
with greater clinical experience.
Histopathology
A focal lesion is characterized by a tumor-like proliferation
of islet cells that push exocrine elements aside or
haphazardly incorporate them (Fig. 109-7). Unlike
insulinomas, the focal lesion retains the lobular architecture
of the normal pancreas, and exocrine elements usually
remain within the lesion. The lesions often have irregular
borders, and the endocrine cells frequently have enlarged
nuclei. Islets outside the lesion appear normal. Patients with
diffuse disease have abnormal islets containing 5% to 10%
of cells with enlarged nuclei present throughout the
pancreas. After the surgery, all frozen samples are
processed for routine histology and confirmation of findings
on the basis of paraffin-embedded sections and insulin
immunohistochemistry.
Surgery
Open operations are approached in a similar manner using a
transverse supraumbilical laparotomy.90–92 The pancreas is
exposed by an extended Kocher maneuver, entry into the
lesser sac, and mobilization of the inferior border of the
pancreas. It is not necessary to mobilize the spleen. The
pancreas is inspected under 3.5 loupe magnification in an
attempt to visualize a focal lesion, and the pancreas is
palpated. If no focal lesion is seen, then 2- to 3-mm-
diameter biopsies are taken each from the pancreatic head,
body, and tail. Patients with suspected diffuse HI have
intraoperative biopsies to confirm the diagnosis and then
undergo near-total pancreatectomy. Near-total
pancreatectomy (95% to 98%) involves resection of the
entire pancreas leaving only a tiny residual piece of the
pancreas between the common bile duct and the duodenum.
The intrapancreatic course of the common bile duct should
be completely dissected for an adequate near-total
1380 PART VII ABDOMEN
pancreatectomy to be performed.90 For children with diffuse
disease treated by near-total pancreatectomy, a gastrostomy
tube is also placed to make it easier to administer
supplemental glucose or night-time feedings if necessary.
When the biopsies demonstrate normal pancreatic
histology, a further search for the focal lesion using the
FIGURE 109-6 Positron emission tomography scan is coregistered with a
computed tomography scan that shows a focal lesion (arrow) in the head of
the pancreas. The kidneys excrete the 18-FluoroDOPA and also light up.
is vitally important. Focal lesions tend to be less than 10 mm
in size (although they can be much larger) and are
frequently irregularly shaped. Some lesions have octopus-
like tentacles that make imperative the intraoperative
confirmation of clear margins by frozen section analysis.
Although focal lesions may maintain a lobular structure
similar to that of the normal pancreas, subtle visual clues
(ranging from a slightly reddish color to a marble-like
appearance) may permit visual detection of the lesion
intraoperatively and accurate preoperative localization
studies greatly facilitate the visual search for a focal lesion.
In some cases the lesion will feel firmer than the
surrounding normal pancreas. However, a tiny focal lesion
can be buried within the pancreas and be impossible to see
or feel. Greater operative experience has led to more
frequent intraoperative visualization or palpation of a focal
lesion. Insulinomas differ from focal lesions because they
are usually straightforward to identify intraoperatively and
occur in older children.
FIGURE109-7 A, Cut surface of pancreatectomy specimen through a focal lesion (marked by suture). B, Chromogranin A immunolabeling highlights the
architecture of the focal lesion (left) and adjacent normal pancreas (right). Comparison of cytologic features of the endocrine tissue in the focal lesion (C) and
normal pancreas (D). Note enlarged islet cell nuclei in C.
Once the focal lesion is identified, a partial
pancreatectomy is performed using frozen sections of
margins to ensure a complete resection. For periductal
lesions in the body and tail, a distal pancreatectomy is
performed. With pancreatic head lesions close to the
common bile duct or pancreatic duct, it can be tricky to
excise all of the lesion, particularly if there are tentacles of
diseased tissue that emanate from the lesion. To ensure
complete lesion resection in these challenging cases, the
surgeon should remove most or all of the pancreatic head
followed by Roux-en-Y pancreaticojejunostomy to drain
the remaining pancreatic body and tail. In this way, the
preoperative localization data is conducted. Additional
biopsies of suspicious areas are obtained until the focal
lesion is diagnosed by frozen section. Expert pediatric
pathologic interpretation
endocrine and exocrine function of the remaining normal
pancreas is saved. In babies the pancreatic duct on the cut
surface of the transected pancreatic body is not visible, so
the end of the Roux-en-Y jejunal limb is meticulously
anastomosed to the capsule of the pancreatic body with fine
interrupted monofilament suture to effectively dunk the cut
end of the pancreas into the small bowel lumen. Rarely, a
focal lesion in the head will extend into the duodenal wall
in which case a Whipple procedure may be necessary.
Because PET scan localization of focal lesions has proven
to be so accurate, focal lesions in the body and tail are now
resected using laparoscopic techniques. The drawback to
the laparoscopic approach is that there is little tactile
feedback to help locate a nonvisible focal lesion.
Because morethan50% offocallesions involve the pancreatic
head, subtotal (50% to 75%) distal pancreatectomy is
inadequate therapy in many of these cases. Our experience with
several referrals who underwent subtotal pancreatectomy
elsewhere with the focal lesion remaining within the residual
pancreas are good examples of this potential pitfall.
Postoperative Care and Follow-up
Postoperative management has been standardized by a clinical
care pathway including the use of the Glucose Infusion Rate to
quantitate the patient’s glucose requirement.85 Glucose Infusion
Rate (GIR) is calculated as % dextrose IV rate 0.169/Wt in
kilograms. For the initial postoperative period, blood glucose
values are determined hourly. The GIR begins at 2 mg/kg/min
immediately postoperatively, is increased to a GIR of 5 on the
morning of postoperative day 1, and then usually advances to a
GIR of 8 by the evening of the first postoperative day. It is not
unusual for an intravenous insulin infusion to be necessary for
the first few postoperative days. After hospital discharge, a
complete response at follow-up is defined as no requirement for
glycemic medications, no continuous tube feedings, no diabetes
mellitus, and the ability to tolerate an 18-hour fast without
hypoglycemia.
In our entire experience, 95% of babies with the focal form
of HI are cured after limited pancreatectomy. The vast majority
had a less than 50% pancreatectomy. For babies with diffuse HI
treated with near-total pancreatectomy (95% to 98%), about one
third require no glycemic medications, one third require insulin
to treat diabetes, and one third require a glycemic medication
(usually octreotide). Long-term follow-up is necessary for all of
these children, particularly with regard to neurodevelopmental
issues.
 CHAPTER 109 THE PANCREAS 1381
cystadenocarcinoma of the pancreas represents 1% of all
Neoplasms malignant conditions of the pancreas, occurs at an earlier
------------------------------------------------------------------------------------------------------------------------------------------------
age than conventional solid pancreatic tumors do, and
Pancreatic neoplasms are relatively rare in infants and children. seems to be approximately half as common as cystadenoma.
They can be cystic, solid, and benign or malignant and may or The clinical and radiologic manifestations of mucinous
may not be hormonally active. In 1990 Grosfeld 93 reported 13 cystadenocarcinoma are similar to those of mucinous
cases of pancreatic tumor in children including 5 insulinomas, cystadenoma. It is not always possible to differentiate
2 mucinous cystadenomas, 2 rhabdomyosarcomas, and 4 mucinous cystadenoma from cystadenocarcinoma
carcinomas. In 1992 Jaksic reported 6 cases of pediatric pathologically. It is also common to find apparently benign
pancreatic tumors,94 and now more than 200 cases have been epithelium103 in the same tumors as malignant epithelium,
reported in the English literature. More recently, pancreatic thus suggesting that a malignant focus may develop within
tumor series have been reported by Shorter (17 cases), 95 Perez a mucinous cystadenoma. Therefore mucinous
(58 cases),96 and Yu (18 cases).97 Unlike malignant pancreatic cystadenoma should be considered a premalignant lesion
tumors in adults, tumors in children and adolescents are usually that should be completely excised after incomplete excision
resectable and long-term survival is likely. or marsupialization.98,103 However, the prognosis for this
form of pancreatic malignancy is significantly better than
that for the common typical solid ductal adenocarcinoma
CYSTIC NEOPLASMS because of its slow growth and lack of metastatic potential.
Cystic neoplasms of the pancreas are relatively rare.98,99
Papillary-Cystic Epithelial Neoplasm
Howard100 classified these lesions into (1) cystadenoma and
cystadenocarcinoma, which include benign (microcystic) The first cases of papillary-cystic endothelial tumors of the
cystadenoma, benign and malignant mucinous (macrocystic) pancreas were reported by Franz in 1959.107 Since these
cystadenoma and cystadenocarcinoma, papillary-cystic tumors were described as solid and cystic acinar cell tumors
epithelial neoplasm, and acinar cell cystadenocarcinoma (not of the pancreas by Kloppel and colleagues,108 increasing
reported in children) and (2) teratomatous cysts. numbers have been reported in children. They occur
predominantly in girls and young women and are
manifested as large, encapsulated masses, usually with
Cystadenoma and Cystadenocarcinoma
extensive necrosis and varying amounts of cystic change.
Cystadenoma of the pancreas is rare in children and adults. Only Histologically, they are composed of solid areas of rather
six cases including one in a newborn have been reported in the small cells with pseudorosette formation reminiscent of
pediatric population to date.93,101,102 Cystadenoma and endocrine tumors and cystic areas with papillary
cystadenocarcinoma should be divided into two groups. structures.109 Immunohistochemically, the tumor cells of
Because large mucinous cystic adenomas have considerable solid and cystic pancreatic neoplasms contain periodic acid-
malignant potential, these tumors should be distinguished from Schiff-positive granules and often have progesterone
serous cystadenomas, which are benign; the latter tumors are receptors. Immunologic hallmarks are immunoreactivity
rich in glycogen and contain little or no mucin.103 with alpha-antitrypsin, alpha-antichymotrypsin,
phospholipase A2, and neuroendocrine markers such as
neuron-specific enolase and synaptophysin. However, they
SerousCystadenomaandCystadenocarcinoma Serous cystic are generally free of the usual markers of pancreatic
neoplasms of the pancreas are rare in children and adults, carcinoma such as carcinoembryonic antigen, CA19-9, and
are more often observed in females, and are found mainly tissue peptide antigen.110 These tumors seem to be
in the body and tail of the pancreas. These tumors consist associated with a much better prognosis than the usual type
predominantly of small cysts (microcystic adenomas).104 of pancreatic carcinoma but still have malignant
Calcification is often demonstrated on CTand US. Serous potential.111 The tumor follows a benign course after
cysts do not need to be excised unless they create a resection in most cases. Metastasis or recurrence has
mechanical obstruction because nearly all of them are occurred in 5% of cases in Japan.112 Thus complete
benign with no malignant potential.105 Biopsy is required. extirpation is necessary because of the slow tumor
Serous cystadenocarcinoma is virtually nonexistent in progression associated with metastatic disease.113 Liver
children, and only a few cases have been reported in adults. metastases have been treated with resection and liver
transplantation.114
Mucinous Cystadenoma and Cystadenocarcinoma
Mucinous cystic neoplasms of the pancreas are usually large Other Cystic Neoplasms in Children
and often multilocular. They form papilla lined with In 1992 Flaherty and Benjamin115 reported a case of
columnar, mucin-producing epithelium; are more often multicystic pancreatic hamartoma in a 20-month-old girl. In
observed in females; and are found mainly in the body and 1990 Mester and colleagues116 reviewed 10 cases of cystic
tail of the pancreas.106 Other features are the association of teratoma of the pancreas including one of their own. Cystic
large blood vessels within the capsule and the presence of teratomas were usually seen as benign extragonadal germ
subepithelial hemorrhage. A common differential diagnosis
is pancreatitis with pseudocyst formation. Mucinous
1382 PART VII ABDOMEN
cell tumors in younger patients; 5 of 10 patients were
younger than 11 years.
HORMONALLY ACTIVE TUMORS
Endocrinologically active tumors are usually identified by
their symptoms, and most of them originate in the islet cells.
Beta-cell tumors secrete insulin; alpha cell tumors,
glucagon; gamma cell tumors, gastrin; delta cell tumors,
somatostatin; and delta1 cell tumors, vasoactive intestinal
polypeptide (VIP) and possibly substance P and secretin.
Glucagonomas and somatostatinomas have not been
identified in children.
Insulinoma
Insulinomas are the most common tumor arising from islet
cells and are usually benign (>90%), solitary (80%) lesions
that occur in children older than 4 years. A plasma
insulinto-glucose ratio greater than 1 is diagnostic (<0.4 is
normal),117 and the ratio increases with fasting.
Concomitant measurement of C peptide levels may be used
to exclude factitious hypoglycemia. CT, US, arteriography,
and transhepatic portal venous sampling can be used to
localize an insulinoma. The tumor is usually discrete and
well encapsulated, and most can be enucleated. The
introduction of endoscopic and intraoperative US has
allowed obscure lesions to be identified. If all methods of
tumor localization are unsuccessful, distal pancreatectomy
with careful sectioning of the gland is advisable. In that
circumstance, measurement of intraoperative insulin levels
is recommended to avoid missing lesions. Virtually all
infants and children with insulinoma can be cured.
Multiple endocrine neoplasia type I (MEN-I) is
characterized by endocrine tissues in the gut and pancreas
including insulin-secreting tumors, but expression is
usually delayed beyond the first decade of life. MEN-I is
rare, with a frequency not exceeding approximately 1 in
10,000. The gene for MEN-I has been localized to the long
arm of chromosome 11 and functions as a tumor suppressor
gene, unrelated to the functional alterations in the
SUR1/Kir6.2 components of KATP on the short arm of
chromosome 11.118
Gastrinoma
The second most commonly reported pancreatic hormonal
tumor is the gamma cell tumor. The clinical syndrome
related to gastrinoma is often referred to as Zollinger-Ellison
syndrome, a condition characterized by hypergastrinemia
with severe peptic ulcer disease. This syndrome is rare in
children.
Gastrinoma is part of the MEN-I syndrome and is commonly
malignant, multicentric, and metastatic at discovery.93 The
diagnosis is usually made after recurrent episodes of peptic
ulceration associated with an elevated gastrin level (>500
pg/mL). Calcium infusion and secretin simulation tests are used
for diagnosis. CT, percutaneous transhepatic venous sampling,
and gastrin assay have been useful for localization. Although
total gastrectomy was originally the most common method of
treatment, the development of inhibitors of gastric acid
secretion such as H2 blockers and omeprazole has changed the
direction of treatment of gastrinoma substantially. Children
with gastrinoma generally require lifelong medical treatment,
and somatostatin, although beneficial because it decreases
gastric acid secretion, also inhibits growth hormone secretion,
so it cannot be used long-term. Surgical treatment should thus
be aggressive, especially if a solitary tumor is found with no
evidence of metastasis at the time of laparotomy. However, total
gastrectomy may still be required for patients in whom medical
treatment has failed or those with residual tumor or metastatic
disease.93
VIPoma
VIPoma in children is far more commonly related to other
neurogenic neoplasms such as neuroblastoma or
ganglioneuroma than to tumors of primary pancreatic origin.
Only a few cases of VIPoma in children have been reported.
The VIP that is produced by a pancreatic VIPoma probably
originates from neural cells in the islets.117 Patients have
profuse, watery diarrhea associated with hypokalemia and
hypochlorhydria (WDHA syndrome), and metabolic acidosis
and prerenal azotemia secondary to dehydration are often
present. Although medical therapy includes the use of
streptozotocin and somatostatin, long-term use of somatostatin
is undesirable. Surgical extirpation of the tumor-bearing gland
is recommended whenever possible because 50% of pancreatic
VIPomas are malignant.93
CARCINOMA
Carcinoma of the pancreas is common in adults but rare in
children. The clinical features are different in that obstructive
jaundice is the primary finding in adults, whereas an abdominal
mass is usually the initial feature in children. Pancreatic
carcinoma in children can be divided into four groups: islet cell
carcinoma, adenocarcinoma, pancreatoblastoma, and
miscellaneous lesions.
Islet Cell Carcinoma
Islet cell carcinoma in children may or may not be functional.
Functioning beta-cell and non–beta-cell islet cell carcinoma
occurs in infants and children with hypoglycemia in conjunction
with Zollinger-Ellison syndrome, but it is not associated with a
palpable mass. A beta-cell carcinoma is usually discovered
during laparotomy for insulinoma. Four functional islet cell
carcinomas have been described in children; all were treated by
surgical extirpation, with good long-term survival.119–121 Seven
of the eight children with Zollinger-Ellison syndrome described
by Wilson had non–beta-cell carcinoma with metastatic
disease.122
Nonfunctioning islet cell carcinomas are more common in
children than adults. Because these tumors are usually
discovered by palpation of an abdominal mass, they are often
diagnosed late, and many affected infants and children have
distant metastatic disease at the time of diagnosis. Most
nonfunctional tumors are large, solitary lesions that can appear
in any location within the gland. In general, although most of
 CHAPTER 109 THE PANCREAS 1383
these tumors grow slowly, aggressive surgical therapy is The complete reference list is available online at www.
warranted because of their malignant potential.123 expertconsult.com.

Adenocarcinoma
Adenocarcinoma of the pancreas is rare in children. Vejcho124
reviewed 37 cases of adenocarcinoma in 1993. The clinical
manifestations differ from those of adults in that the incidence
of pain with jaundice is lower.121 Abdominal pain and a palpable
epigastric mass are the primary findings in children.
Classification is still controversial and is based on tumor
activity and histopathologic and immunohistochemical
findings. Kloppel classified adenocarcinoma into three types:
acinar cell carcinoma, solid and cystic tumor (papillary cystic
tumor), and pancreatoblastoma.108 Acinar cell tumors are
proportionately more common in children.111 It seems that
children with an acinar cell tumor have a somewhat better
prognosis than do those with an adenocarcinoma of the duct cell
type. The prognosis for children with adenocarcinoma of the
duct cell type is discouraging and similar to that for adults. CT
and sonography are useful for diagnosis. For localized lesions,
pancreaticoduodenectomy seems to be associated with a
favorable prognosis. Infants and children tolerate radical
resection of the pancreas somewhat better than adults do and
have a lower mortality rate and better long-term survival.
Pancreatoblastoma
In 1977 Horie125 reported two cases of pancreatic carcinoma,
which they termed pancreatoblastoma, an infantile type of
pancreatic carcinoma. In 1984 Buchino126 reviewed eight
patients with pancreatoblastoma, six of whom survived after
surgical extirpation. Pancreatoblastoma is the most common
pancreatic neoplasm in young children. Pancreatoblastomas
have a better prognosis than adenocarcinoma because they have
an encapsulated organoid structure that does not directly
interfere with the main duct system. The criteria for diagnosing
pancreatoblastoma have been described.126–128 Although there is
no agreement on the pathology of these rare lesions,
terminology based on recognizable lines of differentiation
seems preferable (e.g., islet cell, duct cell, acinar cell,
undifferentiated lesions).111 The recurrence risk after resection
is high. These tumors can be responsive to chemotherapy and
radiation, but the appropriate role for these modalities is
unknown.

Miscellaneous Carcinomas
The following miscellaneous carcinomas in children have
been reported in the literature: one case of carcinoma
simplex; one case of medullary carcinoma129; six cases of
sarcoma (two lymphosarcomas,129 two with sarcomatous
degeneration from cystadenoma,93,130 and two
93
rhabdomyosarcomas ); four cases of undifferentiated
carcinoma121,126; and two cases of cylindrical cell
adenocarcinoma.131

Acknowledgments
This revised chapter based on the version written by Takeshi Miyano that
appears in the sixth edition.