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Coran - PS, 7th - 109 - The Pancreas
Coran - PS, 7th - 109 - The Pancreas
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
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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
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Etiology
Surgical Anatomy Although pancreatitis in adults is usually related to alcohol
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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
CHAPTER 109 THE PANCREAS 1373
Systemic infection iatrogenically induced during the course of abdominal
Mumps surgery or ERCP.30
Rubella Drugs cause 8% to 25% of the cases of pancreatitis.
Coxsackie B virus
Drugs that cause pancreatitis most frequently include
Trauma
didanosine, azathioprine, mercaptopurine, L-asparaginase,
Blunt abdominal trauma
and valproic acid.20,31,32 Recently, liver transplantation has
Iatrogenic (e.g., surgery, ERCP)
been reported as a possible cause of acute pancreatitis. The
Anomalies of the pancreaticobiliary duct system
Pancreaticobiliary malunion
incidence of this complication and the mortality rate in
Pancreas divisum
children were 1.9% and 43%, respectively.33 A strong
Hypertensive sphincter of Oddi association between the development of acute pancreatitis
Choledochal cyst after liver transplantation and several risk factors such as
Choledocholithiasis the diagnosis of fulminant hepatic failure, retransplantation,
Drugs extensive dissection at the time of liver transplantation, and
Azathioprine the use of infrarenal arterial grafts has been reported. 34
Tetracycline Certain variants of the trypsinogen gene and cystic
L-Asparaginase fibrosis transmembrane regulation (CFTR) gene may cause
Immunosuppressants acute recurrent pancreatitis. Many patients with the
Valproic acid diagnosis of idiopathic pancreatitis have compound
Metabolic abnormalities heterozygote genotypes in which both alleles of the CFTR
Hypertriglyceridemia gene are abnormal, thus constituting a variant of cystic
Hypercalcemia fibrosis. There are also numerous reports of an association
Cystic fibrosis between chronic pancreatitis and a number of CFTR
Liver transplantation
mutations both in patients with cystic fibrosis and in carriers
Miscellaneous
with a single mutation.35
Idiopathic
In certain conditions, destruction of the pancreas begins
ERCP, Endoscopic retrograde cholangiopancreatography. antenatally. Infants with Shwachman-Diamond syndrome,
disease, metabolic disorders, and miscellaneous conditions an autosomal recessive disorder mapped to the centromeric
such as familial pancreatitis and Crohn disease. region of chromosome 7,36 have pancreatic insufficiency at
Six percent to 33% of cases of pancreatitis are related to birth, generally with low serum trypsinogen levels,
disorders of the biliary or pancreatic duct,20 with indicative of nearly total exocrine pancreatic atrophy by
choledochal cyst and cholelithiasis being the most common. birth.
A choledochal cyst is often associated with malunion of the Diagnosis
pancreatic and biliary ducts (pancreaticobiliary malunion), The diagnosis of acute pancreatitis is based on the clinical
and a long common channel may form and permit reflux of history, physical examination, laboratory test results, and
bile into the pancreatic duct.21 The common channel is seen findings of diagnostic imaging investigations. Determination of
easily on ERCP; this channel is often dilated and contains amylase isoenzymes has also been used to increase diagnostic
protein plugs or stones, which may cause obstructive accuracy by identifying the tissue from which the amylase
pancreatitis or jaundice. originates. Serum lipase levels may also complement
Cholelithiasis in children is frequently associated with pancreatitis testing and increase the yield of positive
various hemolytic disorders including spherocytosis, diagnoses.37 A new scoring system for acute pancreatitis in
alphathalassemia, and sickle cell disease. It may also be children has been proposed that has better sensitivity than the
caused by obesity and the use of total parenteral nutrition.22 Ranson and Glasgow scores.22 The parameters are age (<7
The role of pancreatic duct anomalies such as pancreatic
years), weight (<23 kg), admission white blood cell count
divisum and stenosis of the ampulla of Vater has only
(>18,500), admission lactate dehydrogenase level (>2000), 48-
recently been appreciated.23–26 Pancreaticobiliary malunion
hour trough Ca2þ level (<8.3 mg/dL), 48-hour trough albumin
not associated with a choledochal cyst is drawing clinical
attention because it tends to be overlooked on level (<2.6 g/dL), 48-hour fluid sequestration (>75 mL/kg/48
ultrasonography; most patients with the disorder have hr), and 48-hour rise in blood urea nitrogen (>5 mg/dL).
recurrent abdominal pain as a result of pancreatitis. 24,26–28 Plain radiographs of the chest and abdomen are obtained to
Tagge and colleagues26 found ductal anomalies in 6 of 61 exclude intestinal perforation. Occasionally radiopaque
(10%) patients with pancreatitis. They noted that patients gallstones, a gas-filled right colon, or a distended loop of small
with ductal abnormalities usually had recurrent episodes intestine (sentinel loop) may be seen. Left basal pleural effusion
and that relapsing or chronic pancreatitis was also is relatively common, and mottling of the lung fields is a sign of
associated with ductal anomalies. systemic cytokine release. Radiographic studies enhanced by
Severe abdominal trauma may cause immediate acute water-soluble contrast of the upper gastrointestinal tract are
symptoms.29 However, less severe trauma may result in a occasionally useful, particularly in cases of trauma when injury
delayed onset and subacute manifestation. Child abuse to the duodenum or small intestine is suspected.
should be considered in all children with acute pancreatitis Ultrasonography (US) and computed tomography (CT) are
who have a vague history.19 Finally, trauma may also be useful for detecting pancreatic abnormalities. Trauma-induced
1374 PART VII ABDOMEN
injuries to abdominal organs, particularly the pancreas, are Standard medical treatment must be used in patients with
readily detected on CT. acute pancreatitis in an attempt to control the disorder before
ERCP is rarely indicated for acute pancreatitis, but it surgical intervention, which is rarely required in children but is
eventually becomes essential in any child who has pancreatitis occasionally performed if the diagnosis is uncertain or a
with an unclear cause.23,26 This technique is useful in cases of complication develops after an acute episode such as a
relapsing pancreatitis associated with pancreaticobiliary pseudocyst or an abscess. Patients with acute pancreatitis
malunion.21,24 ERCP is an invasive method that can aggravate associated with underlying pancreaticobiliary disease generally
pancreatitis and is often not an option during the acute phase of require surgical correction of the underlying condition before
pancreatitis. Magnetic resonance cholangiopancreatography cure can be expected.
(MRCP) is a noninvasive method of obtaining images of the In the management of severe acute pancreatitis, a major
pancreaticobiliary tract. MRCP images the common bile duct in decision is whether and when surgery for pancreatic necrosis or
more than 96% of patients and detects common bile duct stones infection is necessary. Infection of necrotic pancreatic tissue is
with a sensitivity of 71% to 100%, thus exceeding the sensitivity the major risk factor for mortality in severe acute pancreatitis
of US (20% to 65%) and CT (45% to 85%). Visualization of the and is an indication for surgery. On the other hand, there is
smaller pancreatic duct is successful in more than 80% of support for nonsurgical conservative management of sterile
patients.37 Miyano and colleagues38 have previously evaluated pancreatic necrosis including antibiotic treatment. The reported
the efficacy of MRCP in pediatric patients with acute death rate is 1.8% with sterile pancreatic necrosis and 24% with
pancreatitis. Patients were divided into two groups. Group 1 infected necrosis.41 Early surgery has been associated with
consisted of seven patients in whom choledochal cysts were increased mortality and should be delayed, if not avoided. 42
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 CHRONIC RELAPSING PANCREATITIS
detected in one patient in group 1 but could not be confirmed in Chronic relapsing pancreatitis is characterized by recurrent
any of the group 2 patients. Dilatation of the main pancreatic episodes of upper abdominal pain associated with varying
duct was detected in one in group 1 and in three in group 2. degrees of pancreatic exocrine and endocrine dysfunction.
These findings indicate that MRCP is a potentially useful Relatively few case series of chronic relapsing pancreatitis in
method for identifying and ruling out structural abnormalities of childhood exist, although it is more frequently being suspected
the pancreaticobiliary tract in children. in children with recurrent episodes of abdominal pain.43–45 The
disease produces a wide variation of progressive and
Treatment
irreversible structural changes in the pancreas.44 At present, the
Treatment of acute pancreatitis has two primary goals: (1) to most controversial aspect of treatment of this disorder is the
minimize any causative factors and (2) to provide meticulous choice of an appropriate surgical procedure.
supportive care including liberal use of analgesics, Causes and Pathophysiology
administration of parenteral fluids, maintenance of nutrition,
In children the most common causes of chronic relapsing
prevention of infection, and inhibition of endocrine and
exocrine activity. pancreatitis are trauma, heredity, systemic disease, and
malformations of the pancreaticobiliary duct such as
Parenteral analgesia with narcotics or nonsteroidal
pancreas divisum, annular pancreas, and
antiinflammatory agents is generally required, even in mild
choledocholithiasis. In addition, various unusual conditions
cases of pancreatitis, because the pain can be extreme. It is
including metabolic disease, endocrine disorders, and
traditional to administer meperidine rather than morphine
inflammatory bowel disease13 may cause the disorder.
because the latter produces ampullary spasm. Although
Causes of chronic relapsing pancreatitis are listed in Table
nasogastric suction is usually initiated to reduce vomiting and
109-3.
abdominal distention, the value of nasogastric decompression is
Certain congenital anomalies affect the pancreas and
questionable, unless the patient is vomiting. Aspiration of
gastric acid may reduce pancreatic exocrine secretion by surrounding tissue, several of which are associated with
limiting the release of secretin. Oral feeding must be withheld chronic relapsing pancreatitis. Obstruction of pancreatic
to reduce pancreatic stimulation. Total parenteral nutrition flow caused by a stenotic papilla of Vater and bile reflux
should be initiated early to avoid malnutrition. 39 In addition, resulting from a common channel are believed to be
responsible for the resultant inflammation, which may be
early placement of a central venous catheter in patients with
severe disease will provide access for aggressive intravascular reversible if the obstruction is relieved. A relatively
common cause of relapsing pancreatitis is pancreas
volume support and nutrition. The hematocrit and serum levels
of glucose and calcium should be measured, and hourly urine divisum,46 in which most of the pancreatic fluid flows
output should be monitored carefully. through the minor duct of Santorini, with the possibility of
a relative obstruction to flow because of anatomy and flow
Although the advantages of prophylactic antibiotics have not
dynamics. Some series have reported an increased incidence
been proved, patients with necrotizing pancreatitis may
of pancreas divisum in patients with idiopathic chronic
benefit.40 Other treatment strategies involving somatostatin,
pancreatitis.46 Annular pancreas, which results from an error
glucagon, anticholinergics, histamine blockers, and protease
of rotation or fixation of the embryologic pancreatic
inhibitors have been recommended, but to date they have not
primordium, has also been associated with chronic
shown conclusive benefit.
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 109-4 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 ascites also being features.
US, CT, and magnetic resonance imaging (MRI) are helpful
Enteric duplication involving the pancreas is rare and
and accurate in diagnosis. These studies are also invaluable for
usually associated with gastric duplication.69 This
evaluating the thickness of the cyst wall and for observing
duplication is most likely to result from failure of regression
changes in the cyst during the ensuing period of treatment (Fig.
of an enteric diverticulum formed from the pancreatic duct.
109-5). ERCP is often useful because it can definitively
Many of the reported cases of enteric duplication involving
determine the status of the pancreatic duct and thus guide
the pancreas communicate with the pancreatic duct, are
surgical interventions.75,76 Rarely, pancreatic pseudocysts can
lined with gastric-type epithelium, and contain ectopic
extend into the mediastinum in children.77
pancreatic tissue in their walls. Pancreatic duplication cysts
have been noted on fetal US.70 Treatment
The most common symptom in these patients is recurrent
Optimal management of a pancreatic pseudocyst remains
abdominal pain, often postprandial. Pancreatitis associated
controversial. Treatment options range from conservative
with enteric duplication cysts is believed to be caused by
medical management to surgical drainage.78 Conventional
obstruction of the pancreatic ducts by viscous secretions
management involves supportive therapy over a 6-week waiting
from the cyst or by blood and debris from peptic ulceration
period, during which time either the cyst resolves spontaneously
within the cyst. In patients without pancreatitis, pain may be
or the cyst wall undergoes fibrous maturation, thereby
caused by tension on the wall of the cyst as a result of
permitting internal surgical drainage to the stomach or jejunum.
accumulation of secretions and muscular contraction. 71 CT
This 6-week interval is what has traditionally been accepted, but
may help identify the location and size of duplication cysts,
CT may demonstrate thickening of the cyst wall sufficient to
as well as any edema of the pancreatic head. ERCP or
hold sutures as early as 3 to 4 weeks. Surgical drainage is
MRCP is useful to outline ductal anatomy and demonstrate
usually performed in adults when necessary but is controversial
any communication between the duplication cyst and the
in children because some pancreatic pseudocysts in this group
pancreatic duct to aid in planning the surgical approach. To
resolve without surgical intervention and have a low risk for
date, virtually all duplication cysts reported in the literature
recurrence. Pseudocysts from nontraumatic etiologies are more
have been treated by extirpation, and some have required
likely to require surgical intervention, whereas traumatic
pancreaticoduodenectomy.69,72
pseudocysts are more amenable to nonoperative treatment. 79
Octreotide acetate, a long-acting analogue of somatostatin, may
facilitate medical management of pancreatic pseudocysts.80
PSEUDOCYSTS A significant risk for complications such as infection or
Clinical Features major hemorrhage in untreated pseudocysts or persistence of
Pancreatic pseudocysts are localized collections of severe symptoms may be an indication for earlier intervention.
pancreatic secretions that do not have an epithelial lining If the patient cannot withstand major surgery, external drainage
and develop after pancreatic injury, inflammation, or duct is preferred. There is significant evidence indicating that
obstruction. The most common causes of pseudocysts in internal drainage, especially transgastric cystogastrostomy or
children are trauma and infection.73 Drug-induced acute Roux-en-Y cystojejunostomy, is effective in the treatment of
pancreatitis such as with valproic acid is also a rare cause pancreatic pseudocyst. Roux-en-Y cystojejunostomy is the most
of pancreatic pseudocyst.74 These cysts typically lie in the widely used internal drainage procedure for this problem and is
lesser sac behind the stomach and are composed of a fibrous associated with the lowest rate of complications and
capsule surrounded by inflamed connective tissue. The recurrence.81
capsule of the cyst may also be formed by neighboring In contrast to this approach, others82,83 have reported that
tissue such as the stomach, duodenum, colon, small percutaneous drainage and endoscopic transmural drainage
intestine, or omentum. Pseudocyst fluid is clear or straw 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
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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. glycemic medications, no continuous tube feedings, no diabetes
mellitus, and the ability to tolerate an 18-hour fast without
hypoglycemia.
Once the focal lesion is identified, a partial In our entire experience, 95% of babies with the focal form
pancreatectomy is performed using frozen sections of of HI are cured after limited pancreatectomy. The vast majority
margins to ensure a complete resection. For periductal had a less than 50% pancreatectomy. For babies with diffuse HI
lesions in the body and tail, a distal pancreatectomy is treated with near-total pancreatectomy (95% to 98%), about one
performed. With pancreatic head lesions close to the third require no glycemic medications, one third require insulin
common bile duct or pancreatic duct, it can be tricky to to treat diabetes, and one third require a glycemic medication
excise all of the lesion, particularly if there are tentacles of (usually octreotide). Long-term follow-up is necessary for all of
diseased tissue that emanate from the lesion. To ensure these children, particularly with regard to neurodevelopmental
complete lesion resection in these challenging cases, the issues.
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
CHAPTER 109 THE PANCREAS 1381
cystadenocarcinoma of the pancreas represents 1% of all
Neoplasms malignant conditions of the pancreas, occurs at an earlier
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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 treatment, the development of inhibitors of gastric acid
younger than 11 years. secretion such as H2 blockers and omeprazole has changed the
direction of treatment of gastrinoma substantially. Children
with gastrinoma generally require lifelong medical treatment,
HORMONALLY ACTIVE TUMORS
and somatostatin, although beneficial because it decreases
Endocrinologically active tumors are usually identified by gastric acid secretion, also inhibits growth hormone secretion,
their symptoms, and most of them originate in the islet cells. so it cannot be used long-term. Surgical treatment should thus
Beta-cell tumors secrete insulin; alpha cell tumors, be aggressive, especially if a solitary tumor is found with no
glucagon; gamma cell tumors, gastrin; delta cell tumors, evidence of metastasis at the time of laparotomy. However, total
somatostatin; and delta1 cell tumors, vasoactive intestinal gastrectomy may still be required for patients in whom medical
polypeptide (VIP) and possibly substance P and secretin. treatment has failed or those with residual tumor or metastatic
Glucagonomas and somatostatinomas have not been disease.93
identified in children.
VIPoma
Insulinoma
VIPoma in children is far more commonly related to other
Insulinomas are the most common tumor arising from islet neurogenic neoplasms such as neuroblastoma or
cells and are usually benign (>90%), solitary (80%) lesions ganglioneuroma than to tumors of primary pancreatic origin.
that occur in children older than 4 years. A plasma Only a few cases of VIPoma in children have been reported.
insulinto-glucose ratio greater than 1 is diagnostic (<0.4 is The VIP that is produced by a pancreatic VIPoma probably
normal),117 and the ratio increases with fasting. originates from neural cells in the islets.117 Patients have
Concomitant measurement of C peptide levels may be used profuse, watery diarrhea associated with hypokalemia and
to exclude factitious hypoglycemia. CT, US, arteriography, hypochlorhydria (WDHA syndrome), and metabolic acidosis
and transhepatic portal venous sampling can be used to and prerenal azotemia secondary to dehydration are often
localize an insulinoma. The tumor is usually discrete and present. Although medical therapy includes the use of
well encapsulated, and most can be enucleated. The streptozotocin and somatostatin, long-term use of somatostatin
introduction of endoscopic and intraoperative US has is undesirable. Surgical extirpation of the tumor-bearing gland
allowed obscure lesions to be identified. If all methods of is recommended whenever possible because 50% of pancreatic
tumor localization are unsuccessful, distal pancreatectomy VIPomas are malignant.93
with careful sectioning of the gland is advisable. In that
circumstance, measurement of intraoperative insulin levels
is recommended to avoid missing lesions. Virtually all CARCINOMA
infants and children with insulinoma can be cured. Carcinoma of the pancreas is common in adults but rare in
Multiple endocrine neoplasia type I (MEN-I) is children. The clinical features are different in that obstructive
characterized by endocrine tissues in the gut and pancreas jaundice is the primary finding in adults, whereas an abdominal
including insulin-secreting tumors, but expression is mass is usually the initial feature in children. Pancreatic
usually delayed beyond the first decade of life. MEN-I is carcinoma in children can be divided into four groups: islet cell
rare, with a frequency not exceeding approximately 1 in carcinoma, adenocarcinoma, pancreatoblastoma, and
10,000. The gene for MEN-I has been localized to the long miscellaneous lesions.
arm of chromosome 11 and functions as a tumor suppressor
gene, unrelated to the functional alterations in the Islet Cell Carcinoma
SUR1/Kir6.2 components of KATP on the short arm of Islet cell carcinoma in children may or may not be functional.
chromosome 11.118 Functioning beta-cell and non–beta-cell islet cell carcinoma
occurs in infants and children with hypoglycemia in conjunction
Gastrinoma with Zollinger-Ellison syndrome, but it is not associated with a
The second most commonly reported pancreatic hormonal palpable mass. A beta-cell carcinoma is usually discovered
tumor is the gamma cell tumor. The clinical syndrome during laparotomy for insulinoma. Four functional islet cell
related to gastrinoma is often referred to as Zollinger-Ellison carcinomas have been described in children; all were treated by
syndrome, a condition characterized by hypergastrinemia surgical extirpation, with good long-term survival.119–121 Seven
with severe peptic ulcer disease. This syndrome is rare in of the eight children with Zollinger-Ellison syndrome described
children. by Wilson had non–beta-cell carcinoma with metastatic
Gastrinoma is part of the MEN-I syndrome and is commonly disease.122
malignant, multicentric, and metastatic at discovery.93 The Nonfunctioning islet cell carcinomas are more common in
diagnosis is usually made after recurrent episodes of peptic children than adults. Because these tumors are usually
ulceration associated with an elevated gastrin level (>500 discovered by palpation of an abdominal mass, they are often
pg/mL). Calcium infusion and secretin simulation tests are used diagnosed late, and many affected infants and children have
for diagnosis. CT, percutaneous transhepatic venous sampling, distant metastatic disease at the time of diagnosis. Most
and gastrin assay have been useful for localization. Although nonfunctional tumors are large, solitary lesions that can appear
total gastrectomy was originally the most common method of 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.