Pediatric Clinics of North America II

Pediatric Clinics of North America
Volume 45 • Number 6 • December 1998

Copyright © 1998 W. B. Saunders Company
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PEDIATRIC SURGERY FOR THE PRIMARY CARE

PEDIATRICIAN, PART II
THE APPROACH TO COMMON ABDOMINAL DIAGNOSES IN

INFANTS AND CHILDREN
Part II
Richard H. Pearl 1 MD
Michael S. Irish 2 MD
Michael G. Caty 2 3 MD
Philip L. Glick 2 3 MD
1
Department of Surgery, The Children's Hospital of Illinois; and the University
of Illinois College of Medicine at Peoria Peoria, Illinois (RHP)
2
Division of Pediatric Surgery of the Children's Hospital of Buffalo (MSI, MGC,
PLG)
3
State University of New York at Buffalo, School of Medicine and Biomedical
Sciences (MGC, PLG) Buffalo, New York
Address reprint requests to

Philip L. Glick, MD
Department of Pediatric Surgery
The Children's Hospital of Buffalo
219 Bryant Street
Buffalo, NY 14222
e-mail: glicklab@acsu.buffalo.edu
SURGICAL DISORDERS ASSOCIATED WITH CONSTIPATION
Hirschsprung's Disease
An original report by Hirschsprung, presented at the Pediatric Congress in Berlin

in 1886 and subsequently published in 1887, focused the attention of clinicians
on the dilated proximal bowel segment in this disease. [49] This paper, titled
"Constipation of the newborn due to dilatation and hypertrophy of the colon,"
effectively (but incorrectly) guided therapy for over 50 years. This can be seen
in Abdominal Surgery of Infancy and Childhood by Ladd and Gross, published in
1941. [68] The coauthors (ostensibly the Fathers of Pediatric Surgery) noted that
the defect was thought to be deficient parasympathetic innervation or overactive
sympathetic innervation to the affected (dilated) bowel. Treatment
recommendations were parasympathetic stimulants, anal dilatation, cecostomy,
local resection of the dilated colon, and total abdominal colectomy (in that order,
performed in a total of 39 patients). We now know that all of these
recommendations were ill-advised and flirt with disaster because they treated the
result of the functional obstruction (the dilated colon) and not the cause.
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Not surprisingly, all three patients treated with colectomy died, and the patients
with segmental resection of the dilated colon had a very high rate of anastomotic
leak and dehiscence. From 1946 to 1949, Ehrenpreis, Bodian and
[27]
colleagues, and Swenson and colleagues, in separate reports, described the

[10] [118]
distal aganglionic segment as the reason for the anorectal dysfunction with
secondary constipation and the proximal dilated colon as a manifestation of this
distal high-pressure zone.
The operations most frequently performed are named for the surgeons who first
described and used them for the treatment of Hirschsprung's disease. These
include Swenson's coloanal anastomosis, [117] Duhamel's side-to-side rectal
colonic anastomosis, [26] and Soave's endorectal pull-through procedure. [113] All
three of these operations have been successfully used and have very similar long-
term results. Major contributions in the diagnosis of Hirschsprung's disease
(rectal punch biopsy, suction rectal biopsy, barium enema evaluation, anorectal
manometry, and special histologic staining techniques) over the past 30 years
have improved our diagnostic accuracy and have allowed Hirschsprung's disease
to most commonly be diagnosed in the newborn period. [102] The genetic factors in
the hereditary component of Hirschsprung's disease is well described and will
continue to evolve as biomolecular gene mapping progresses. [92]
Epidemiology and Anatomy
Congenital megacolon is caused by failure of migration of enteric ganglia

derived from the neural crest cells. This migration occurs from cranial to caudal
and explains why the anus (just above the dentate line) is always involved in
Hirschsprung's disease. As the lack of nerve connections moves proximally,
progressively more colon is involved. In 75% of cases, the rectosigmoid area is
involved, 15% to 20% extends variably to the rest of the colon, and in the most
severe cases the entire colon (5%-10%) or the entire intestinal tract (<1%) can be
affected. This progressive failure of migration of neural crest-derived
connections explains why no skip areas are found in patients with Hirschsprung's
disease and why once the transition zone is accurately identified (by biopsy), the
definitive resection and surgical reconstruction of the gastrointestinal (GI) tract
can be performed.
The understanding of the effect of proper versus diseased innervation of the GI

tract is central to the correct assessment and proper treatment of the clinical
findings of Hirschsprung's disease. The static (unstimulated) condition of the
intestine is the contracted position. Peristaltic waves are not stimulated
contractions, but stimulated relaxations propagated in a proximal-to-distal
sequence. Therefore, the unstimulated intestinal segments affected by
Hirschsprung's disease remain in the contracted position, causing a pseudo-
obstruction secondary to this high-pressure zone of passive contraction. The lack
of understanding of this anatomic and physiologic phenomenon led to the
surgical misadventures before 1948, when treatment was focused on the normal
(but dilated) proximal colon.
The incidence of Hirschsprung's disease is 1 in 5000 live births and has a male-
to-female predominance of 4:1; however, in long-segment Hirschsprung's disease
(total colon) this is not the case with a male-to-female ratio approaching 1:1. No
racial predilection exists for this disease, and affected infants are usually term
babies of good size. The genetic predisposition of Hirschsprung's disease is well
described, with a familial component responsible for 10% of cases. In addition,
genetic involvement of the RET proto-oncogene has been implicated
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in 50% of familial cases and 15% of sporadic cases. Other associations are
reported with trisomy 21, MEN 2A and the endothelin 3 genes (in connection
with Waardenburg's syndrome). In countries with increased levels of
consanguinity (i.e., Oman and Saudi Arabia), the reported incidence of
Hirschsprung's disease increases to 1 in 1800, with an 11% incidence of Down
syndrome. [5] [17] [92] [93] [102] [105]
Clinical Findings at Presentation
History
With an increasing number of cases diagnosed in the newborn period, failure to

pass meconium in the first 24 to 48 hours of life is the most consistent finding
(95%). These babies can appear well, and with early discharge postdelivery, the
diagnosis can be missed in the newborn nursery. In other newborns, the
symptoms progress more quickly, and low intestinal obstruction is manifested by
a history of abdominal distention, vomiting (which may become bilious or
feculent), and obstipation. The most severely affected infants can present with a
history of lethargy, fever, obtundation, and even profound shock. These infants
(suffering from Hirschsprung's enterocolitis) can be confused with many other
disorders causing neonatal sepsis with ileus in the newborn period and can be a
diagnostic dilemma. In the cases not appreciated at birth, most are diagnosed
before 2 years of age. These patients present with refractory constipation treated
with multiple dietary manipulations, cathartics, and enemas. A history of stools
being produced only with stimulation and rarely occurring spontaneously is
common. In addition, the quality of the stools is either occasional and massive or
more frequent and pelletlike. Rarely, parents describe stools as normal in caliber
and consistency; the stools have a characteristic pungent odor. Surgical
consultation is sought often after lengthy attempts at medical management have
failed. In summary, the key historical findings in patients with Hirschsprung's
disease are failure to pass meconium, abdominal distention,
onstipation/obstipation, vomiting, lethargy, enterocolitis, and perforation.
Of note, even in older patients, when reviewing the birth history, failure to pass
meconium during the first day of life is frequently elicited. [90] [92] [102] [111] [119]
Physical Examination
The physical findings present are determined by the age at presentation and the
severity of the illness. In the newborn period, well, but constipated, infants have
distended, soft abdomens with normal or hyperactive bowel sounds. Rectal
examination is often very helpful. The examiner will sense slightly increased
pressure on the examining finger but no stenosis or obstruction. The ampulla is
frequently empty; however, when the examining finger is removed, an explosive
evacuation of stool and gas often follows, which to the uninitiated can be quite
surprising.
More ill newborns are more distended with tense abdomens but without
peritoneal signs unless perforation has occurred. These infants often react
minimally to the examiner and can be quite lethargic. Fever; tachycardia; and,
most ominously hypotension can be present.
Older infants and children have chronically distended, nontender abdomens with
large fecal masses, usually on the left side. Rectal examinations can be
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unremarkable, the ampulla may be empty, and anal tone appears normal.
Infrequently, explosive stools are produced after the examination as in newborns.
Diagnostic Studies
The critical diagnostic tests are anorectal manometry and histologic examination
of the rectal biopsy segment.
Anorectal manometry measures the reaction of the internal anal sphincter, the
most distal smooth muscle segment of the GI tract (aganglionic in all cases of
Hirschsprung's disease), to balloon distention of the rectum. The normal reaction
to this filling of the rectum is internal anal sphincter relaxation. In patients with
Hirschsprung's disease, either failure of relaxation or paradoxic increase in
internal anal sphincter pressure with rectal distention is present. Early work
suggested that manometry was not accurate in the newborn period; however, with
improved equipment and study techniques, this is no longer the case. The
positive predictive value is more than 90% (failure of relaxation), and false-
negatives are virtually nil (normal response with relaxation). [73] [129] Therefore,
this is a very important and reliable screening test for Hirschsprung's disease
because it may be performed at the bedside, is noninvasive, and is without
complications.
The required diagnostic test to diagnose Hirschsprung's disease is a rectal biopsy

revealing the absence of ganglion cells. This can be accomplished by rectal
suction biopsy, rectal punch biopsy, or operative full-thickness biopsy. The
technical improvements in rectal suction biopsy make this the preferred method
at most centers. Specimens should be taken at three locations for quality control,
and improved diagnostic accuracy (usually 2, 4, and 6 cm above the dentate line).
This procedure is done at the bedside and rarely causes perforation (< 1%). The
only caveat of this technique is the difficulty pathologists experience in
determining whether sufficient submucosa is present in the specimen to reliably
diagnose Hirschsprung's disease on hematoxylin and eosin staining; however,
newer histochemical techniques have ameliorated this concern and made the
diagnostic reliability of this procedure much more certain. Acetylcholinesterase
staining is the most widely used technique and in combination with hematoxylin
and eosin staining is the current standard. The pathologic findings of absent
ganglion cells, hypertrophied nerve, and adequate submucosa are diagnostic for
Hirschsprung's disease. Newer techniques include nitric oxide synthase markers,
neural cell adhesion molecules, and NADPH diaphorase histochemistry (which
can be done intraoperatively). Recent work shows that rectal biopsy specimens
held at 4°C can be stored for as many as 14 days and still reliably have
acetylcholinesterase staining techniques. This allows smaller centers to transfer
specimens and gain the reliability of using this technology. [15] [66]
Rectal punch biopsies, first described in 1972, are safe, reliable, and also
virtually complication free while providing a deeper specimen. The specimen is
obtained in the newborn nursery using a rectal speculum and tonsil biopsy
forceps. One deep specimen is obtained posteriorly, 2 cm above the dentate line,
and is sent for quick section. A rectal pack, expelled spontaneously in several
hours, is all that is needed. Rarely, postprocedure bleeding is problematic (<
1%). [108] With the two techniques described, operative biopsy is only required in
emergency cases performed for perforation, obstruction, or sepsis before
diagnosis and for leveling biopsies performed at the time of definitive surgery.
In virtually all cases of suspected Hirschsprung's disease, a plain abdominal

radiograph is obtained. In neonates, this frequently reveals distended bowel
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loops with an abrupt cut-off below the pelvic brim. A lateral film can be helpful
in this regard, revealing a relatively airless rectum. Rectal examinations before
this study can distort the result. Later in the course, increased signs of obstruction
with air-fluid levels occur. In seriously ill infants with enterocolitis, grossly
distended bowel loops with bowel wall thickening suggestive of edema are noted.
Those most seriously affected may have perforation with obvious free air in the
abdomen. The next test should be expedient laparotomy.
After plain films, most children have dilute barium or water-soluble enema
studies. This test should be performed gently and slowly under fluoroscopic
control to minimize the chance for perforation. The postevacuation or delayed
(24-hour) film frequently reveals the transition zone virtually diagnostic for
Hirschsprung's disease. Centers that prefer water-soluble contrast do so to
prevent the chance for barium peritonitis if perforation occurs. [84]
Special Diagnostic Concerns
Total colon Hirschsprung's disease and ultrashort-segment Hirschsprung's disease

can create diagnostic challenges that should be mentioned. With total colon
Hirschsprung's disease, patients may initially present with cecal or ileal
perforation as newborns. Therefore, a biopsy for ganglion cells should routinely
be performed during the exploratory laparotomy. If Hirschsprung's disease is
diagnosed, an ileostomy is indicated. In less severe cases, the barium enema does
not reveal a transition zone in the colon, and the caliber of the bowel often
appears normal. This can cause a delay in diagnosis. In these cases, manometry
or biopsy is indicated even with a normal contrast study. Surprisingly,
some children with total colonic disease are not detected during the newborn
period and can present with anything from troublesome constipation to profound
enterocolitis with septic shock. As with any disease, a careful history should lead
the practitioner to consider total colon Hirschsprung's disease in what may
otherwise be a confusing picture.
With ultrashort-segment Hirschsprung's disease, children usually have been seen

and treated by many practitioners for persistent constipation with a history of
normal radiologic evaluation and a noncontributory physical examination. The
key here is manometry, which will be abnormal (an absent relaxation reflex),
combined with a rectal biopsy that frequently reveals ganglion cells (remember
this was taken 2 cm above the dentate line and the affected bowel may be distal
to this point). This combination is highly suggestive of ultrashort-segment
Hirschsprung's disease.
Differential Diagnosis
Hirschsprung's disease in the newborn period can present similarly to other

congenital obstructive GI tract diseases. The differential diagnosis of
Hirschsprung's disease includes:
Infants presenting with obstructive symptoms:
Atresia (anal, colonic, jejunoileal)

Cystic masses (ovarian, mesenteric, renal)
Meconium plug syndrome or ileus (cystic fibrosis)
Gastrointestinal tract duplication
Incarcerated hernia (inguinal or internal)
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Small left colon syndrome
Seriously ill infants with obstruction:
Malrotation with volvulus
Necrotizing enterocolitis
Meconium peritonitis
Metabolic conditions
Hypothyroidism
Electrolyte abnormalities
Maternal cocaine or heroin use
Sepsis with ileus
Many of these diseases, infants are usually well, and symptoms relate to lack of
meconium passage. The workup to differentiate these entities from
Hirschsprung's disease consists of contrast enema studies and sonography. The
contrast studies diagnose (and sometimes cure) meconium ileus and plug
syndromes and define GI tract atresias and small left colon syndrome. The abrupt
cutoff caused by incarcerated hernias coupled with physical findings in the groin
should be unmistakable. Sonography is very helpful in defining cystic masses
causing extrinsic obstruction, such as duplications and mesenteric cysts.
In more seriously ill infants, conditions to be considered in the differential

diagnosis usually reveal themselves via historical factors (i.e., bilious vomiting in
malrotation or maternal history), presentation factors (i.e., pneumatosis
intestinalis in necrotizing enterocolitis [NEC] or in utero bowel obstruction in
meconium peritonitis), or with appropriate radiologic and laboratory parameters
coupled with a thorough physical examination. Because operations for
Hirschsprung's disease are principally elective and malrotation with volvulus or
NEC can be surgical emergencies, expeditious resuscitation and radiologic
contrast studies are required to delineate these issues.
In older children, Hirschsprung's disease is frequently confused with functional

constipation; however, findings more frequently seen with constipation (and not
seen in Hirschsprung's disease) include: encopresis, nondistended abdomen,
rectal vault full of stool, no transition zone on barium enema, and normal
manometry.
Treatment
In all cases of Hirschsprung's disease, operative intervention is the definitive

treatment. The current debate on therapy deals with one-stage repair in the
newborn period (open or laparoscopic) versus the conventional multistage repair
requiring colostomy and staged reconstruction. The details of the three major
operations (i.e., Swenson, Duhamel, and Soave) are not germane to this text
except to note that if individual surgeons' or centers' selection bias is eliminated
and comparisons are made of large groups of patients receiving the three
operations, the results are virtually identical. In addition, all three procedures can
be done in a single stage in the newborn period, open or laparoscopically. Critical
review of the literature suggests the following:
One-stage repair is feasible in all patients, including newborns less than 4

kg and less than 30 days of age.
The complications pertaining to colostomy creation and removal are

eliminated (upwards of 25% morbidity alone is related to the colostomy).
Overall health care dollars are decreased per patient treated in one-stage
repairs.
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Outcome studies reveal similar complication rates and functional results

comparing one-stage to multistage procedures.
The ability to perform one-stage repairs is dependent not only on surgeons'
experience with the procedure but also on the experience of pathologists.
Therefore, the authors' current recommendations on treatment for Hirschsprung's

disease in stable, elective patients is one-stage repair in the newborn period
without colostomy. Preoperatively, rectal irrigation and anal dilation should be
done to clean out the GI tract and prevent enterocolitis. Staged repairs should be
reserved for unstable, septic patients requiring urgent fecal diversion or
older children with massive GI tract dilation requiring defunctionalization to
shrink the GI tract before definitive reconstruction. *
The issue of open versus laparoscopic one-stage procedures is not as clear.

Although the cosmetic aspects of laparoscopic repairs are somewhat better, with
low, transverse, small incisions, there need not be much difference. As with
many laparoscopic procedures, operating time is increased, and hospitalization
time and time to GI tract function are usually decreased. Long-term follow-up
data in large comparative series are needed to assess the real differences long-
and short-term with these two modes of surgical therapy. The technical operation
received by the patient does not differ irrespective of the method chosen to
perform it. [24] [36] [37] [95] [101]
Two areas of special concern are total colon Hirschsprung's disease and
ultrashort-segment Hirschsprung's disease. In total colon Hirschsprung's disease,
although many different surgical procedures are espoused, a Duhamel procedure
with side-to-side stapled ileorectal anastomosis is the authors' preference. It has a
low complication rate, is far less technically challenging than some of the more
complex procedures, and can be safely performed in a single stage during the
newborn period. In ultrashort-segment Hirschsprung's disease, a full-thickness,
generous (2-3 cm in length) internal anal sphincter myectomy is both diagnostic
(by evaluating the entire removed muscle strip for ganglion cells) and
therapeutic. It is technically simple, can be performed on an outpatient basis, and
has good to excellent results.
Long-Term Complications, Prognosis, and Follow-Up
As previously described, evaluation of long-term results for all three operations is

relatively similar. Approximately 65% to 85% of patients eventually achieve
excellent results with normal bowel habits, no soiling, and infrequent
constipation. An additional 15% to 20% of patients report troublesome
constipation, occasional soiling, and infrequent incontinence. In 5% to 10% of
patients, severe constipation or incontinence is a long-term issue. The treatment
of constipation in the postoperative period is principally dietary manipulation,
stool softeners, laxatives, and occasionally anal dilatation. A few patients require
routine enemas or operative internal anal sphincterotomy, which, if indicated, can
be curative.
In incontinent patients, manometric evaluation may reveal poor sphincter

function (internal, external, or both). If this is the case, purposeful constipation
with prograde (via a cecostomy tube or Malone procedure) or retrograde enemas
provide for social, but not physiologic, continence.
Approximately 25% of children in most large series receive reoperation for
*References [16] [46] [70] [83] [87] [121] [123] [127]
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stenosis, prolapse, bowel obstruction, abscess drainage, sphincterotomy, or

(rarely) surgical revision. The incidence of reoperation should decrease with the
elimination of the routine use of colostomy diversion. In all reports,
neurologically impaired children or those with trisomy 21 fare far worse than
their normal peers, with a twofold or threefold increase in incontinence or severe
constipation. In all long-term reports, over time, continence rates improve
progressively. Therefore, long-term detailed follow-up is indicated and required
for all patients to achieve the most satisfactory outcomes. *
A special caution for those with total colon Hirschsprung's disease is that
these children often have some degree of failure to thrive and can develop iron
deficiency anemia and decreased B12 levels. Vitamin supplements, monthly
B12 injections, and routine laboratory and nutritional assessment are indicated. [57]
Hirschsprung's Enterocolitis
Hirschsprung's enterocolitis can occur preoperatively and postoperatively (either

after colostomy or definitive repair). The reported incidence varies from 20% to
60%, and in older reports it was the principal cause of mortality in Hirschsprung's
disease. With increased awareness and early recognition, mortality from
Hirschsprung's enterocolitis is now uncommon. The clinical triad of explosive
watery diarrhea, abdominal distention, and fever should presumptively diagnose
Hirschsprung's enterocolitis in patients known to have Hirschsprung's disease.
Positive stool and blood cultures are uncommon and do not aid in diagnostic
accuracy or treatment. On presentation, these children should have immediate
intravenous rehydration; frequent rectal irrigation with warm, normal saline; and
intravenous metronidazole. Virtually all patients respond to this therapy.
In the preoperative period, the cause of Hirschsprung's enterocolitis is thought to

be increased intraluminal pressure in the colon above the transition zone causing
relative ischemia in the distended bowel wall with transmigration of colonic
bacteria; however, causative agents, such as Clostridium difficile, Staphylococcus
aureus, and rotavirus suggest that other factors may pertain because these are not
the principal flora of the colon. Other factors described relate to changes in the
mucin production and the intrinsic barrier function of the bowel wall. [6] [30] [45] [77]
A recent report evaluating postoperative factors causing Hirschsprung's

enterocolitis revealed patient factors (e.g., sex, age, and weight at surgery) and
technical factors (e.g., choice of operation, number of stages and length of
involved bowel, presence of preoperative Hirschsprung's enterocolitis) had no
effect on the incidence of Hirschsprung's enterocolitis postoperatively; however,
mechanical factors (e.g., anastomotic stricture or leak and intestinal obstruction)
were predictive of a 2.8- to 3.5-fold increase in Hirschsprung's enterocolitis.
Therefore, frequent rectal dilation postoperatively to avoid stricture formation,
one-stage repairs (which may decrease the frequency of bowel obstructions), and
rectal irrigation for several weeks to months after surgery may aid in decreasing
the incidence of Hirschsprung's enterocolitis in the postoperative period. [45]
SURGICAL DISORDERS ASSOCIATED WITH BLEEDING
Gastrointestinal bleeding is a rare occurrence in pediatric patients. In this patient

population, minor bleeding sources are usually benign, resolve nonoperatively,
*References [34] [47] [48] [59] [78] [81] [91] [96] [97] [110]
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and are more common than lesions causing major blood loss. Differential
diagnosis can be simplified by considering common causes of bleeding stratified
by age (Table 1) . The following discussion divides GI bleeding into upper and
lower GI lesions.
Definitions
It is important to be precise when describing the patient with gastrointestinal

hemorrhage. Characteristics of vomited blood, or blood passed per rectum, are
the first clinical "clues" as to the source, quantity, and duration of bleeding.
Hematemesis is the vomiting of blood and implies a source proximal to the
ligament of Treitz. Vomited blood may have the appearance of coffee grounds or
may be bright red in color, implying ongoing bleeding. Blood from the upper GI
tract or proximal small bowel, when passed per rectum, is typically black or
tarry, sticky, and has a characteristic aroma. This is called melena. Dark stools
may be differentiated from melena by a guaiac occult fecal blood test. Bright red
blood per rectum or maroon stools (hematochezia) imply a more distal GI source
or a shorter transit time of blood from a briskly bleeding proximal source.
TABLE 1 -- COMMON CAUSES OF UPPER GASTROINTESTINAL HEMORRHAGE

IN CHILDREN
From Caty MG, Azizkhan RG: Gastrointestinal bleeding. In Oldham KT, Colombani PM,
Foglia RP (eds): Surgery of Infants and Children: Scientific Principles and Practice.
Philadelphia, Lippincott-Raven, 1997, pp 1125-1131; with permission.
Upper Gastrointestinal Lower Gastrointestinal
Age Tract Tract
Newborn (0-30 days) Gastritis Necrotizing entercolitis
Swallowed maternal blood Malrotation with midgut
volvulus
Anal fissure
Hirschsprung's disease with
enterocolitis
Infant (30 days-1 y) Gastritis Anal fissure
Esophagitis Allergic proctocolitis
Peptic ulcer disease Intussusception
Meckel's diverticulum
Lymphonodular hyperplasia
Intestinal duplication
Preschool (1-5 y) Gastritis Juvenile polyps
Esophagitis Lymphonodular hyperplasia
Peptic ulcer disease Meckel's diverticulum
TABLE 1 -- COMMON CAUSES OF UPPER GASTROINTESTINAL HEMORRHAGE
IN CHILDREN
From Caty MG, Azizkhan RG: Gastrointestinal bleeding. In Oldham KT, Colombani PM,
Foglia RP (eds): Surgery of Infants and Children: Scientific Principles and Practice.
Philadelphia, Lippincott-Raven, 1997, pp 1125-1131; with permission.
Upper Gastrointestinal Lower Gastrointestinal
Age Tract Tract
Esophageal varices Hemolytic uremic syndrome
Henoch-Schonlein purpura
Infectious colitis
School age and adolescent Esophageal varices Inflammatory bowel disease
Peptic ulcer disease
Infectious colitis
Juvenile polyps
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Initial Evaluation
The initial evaluation of all infants and children with GI bleeding includes a
focused history and examination but should not delay resuscitation. A past
history of bleeding, as well as a family history of bleeding disorders, medications
that may affect platelet function or coagulation, and a thorough medical and
surgical history are obtained. Recently ingested food (red food coloring in juices
or medications) may resemble blood when vomited. Iron in foods (e.g., red meat
or spinach) or in vitamin supplements may cause dark stools and can be confused
with melena.
Physical examination in the patient suspected of having GI bleeding includes

examination from the oropharynx to the anus. Examination of the mouth for
erosions or pigmented lesions (Peutz-Jegher's syndrome) and nose (epistaxis)
should be performed. In addition to abdominal distention (ascites) and
hepatosplenomegaly, extra-abdominal signs of portal hypertension should be
sought in patients with known or suspected liver disease (e.g., icterus, caput
medusae, or cutaneous spider nevi). Soft tissue tumors or bone tumors suggest
Gardner's syndrome and congenital polyposis. An abdominal examination and
rectal/guaiac examination are also completed.
A nasogastric tube to help prevent aspiration and to ascertain whether the

bleeding is prepyloric or postpyloric should be passed in all patients with GI
bleeding. Blood for complete blood count, platelet count, PT, and APTT should
be drawn from the patient or intravenous access lines before initiating fluid
resuscitation.
Resuscitation
The magnitude of bleeding is reflected in the physiologic status of

these children, and resuscitative efforts should be initiated based on physiologic
criteria and not laboratory data. Whereas otherwise healthy children may tolerate
up to a 10% blood loss (blood volume/body weight) with only a minimal
elevation in heart rate, 10% to 20% blood loss usually results in tachycardia and
orthostatic hypotension. With 30% blood loss, hypotension and poor capillary
refill ensue.
Two, large-bore peripheral intravenous catheters should be placed, and

crystalloid resuscitation begun (20 mL/kg initially). Patients with evidence of
ongoing bleeding or who fail to respond to crystalloid resuscitation should
undergo transfusion, and a pediatric surgeon should be consulted.
The diagnostic approach to upper GI bleeding (Figs. 1 and 2) and lower GI

bleeding (Figs. 3 and 4) may be simplified by considering the history and
physical findings with a differential diagnosis common to the age of the
patient (Table 1) .
Upper Gastrointestinal Bleeding
Upper GI bleeding results in "coffee ground" emesis, hematemesis, melena, or

hematochezia. Fortunately, GI bleeding in neonates is usually benign and self-
limited. The presence of significant upper GI bleeding can be established by
placement of a nasogastric tube. Inability to clear the stomach with saline lavage
implies ongoing bleeding. Establishment of ongoing bleeding mandates
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Figure 1. Diagnostic approach to upper gastrointestinal hemorrhage in infants
and children. ( From Caty MG, Azizkhan RG: Gastrointestinal bleeding. In Oldham
KT, Colombani PM, Foglia RP (eds): Surgery of Infants and Children: Scientific
Principles and Practice. Philadelphia, Lippincott-Raven, 1997, pp 1125-1131; with
permission.)
resuscitation of these children and transfer to the intensive care unit for
monitoring and endoscopic diagnosis.
A full-term infant with hematemesis may have swallowed maternal blood during
delivery. This may be diagnosed with the alum-precipitated toxoid (APT) test:
gastric content of the neonate containing blood is mixed with 1% sodium
Figure 2. Diagnostic approach to upper gastrointestinal hemorrhage in children and

adolescents. ( From Caty MG, Azizkhan RG: Gastrointestinal bleeding. In Oldham
permission.)
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Figure 3. Diagnostic approach to lower gastrointestinal hemorrhage in infants

and children. ( From Caty MG, Azizkhan RG: Gastrointestinal bleeding. In Oldham
permission.)
hydroxide; fetal hemoglobin, resistant to reduction, remains a pink or bright red

color, whereas maternal hemoglobin reduces, turning a brown or rusty color.
Confirmation of swallowed maternal blood requires no additional investigation
or treatment.
Esophagitis in infants and children usually occurs as a result of gastroesphageal

reflux and rarely causes hematemesis but may result in occult blood loss and
anemia. [18] If gastroesophageal reflux is documented, medical management with
antacids or H2 blockers is initiated. If conservative management fails, the patient
is referred for an antireflux procedure.
Most newborns and infants with gastritis, gastroduodenal ulceration, or both,
Figure 4. Diagnostic approach to lower gastrointestinal hemorrhage in children and

adolescents. ( From Caty MG, Azizkhan RG: Gastrointestinal bleeding. In Oldham
permission.)
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have a coexisting condition, such as prematurity, burns (Curling's ulcer), a brain

tumor, head trauma (Cushing's ulcer), or sepsis. Stress gastritis with or without
gastroduodenal ulceration presents with hematemesis, heme-positive gastric
aspirates, or melena. For acute bleeding, a nasogastric tube is placed, and the
stomach is lavaged with room temperature normal saline. Diffuse gastritis is
ideally managed medically with correction of any coagulopathy and
H2 antagonists (ranitidine), cytoprotective agents (sucralfate), or H+ /K+ ATPase
inhibitors (omeprazole). Ongoing bleeding should prompt investigation and
correction of correctable causes of stress (i.e., infection). Failure of conservative
management warrants gastrotomy. On rare occasion gastric resection necessary
in the pediatric population.
Most patients with peptic ulcer disease can be successfully treated with medical
therapy. Operation is necessary only for unremitting bleeding and chronic ulcer
disease. Variceal hemorrhage may result in life-threatening bleeding. It is readily
identified with upper endoscopy. Therapeutic endoscopy using either variceal
injection or banding is usually successful in stopping the bleeding. The rare
patient requires portal-systemic decompressive surgery.
Lower Gastrointestinal Bleeding
Lower GI bleeding in neonates and infants results from lesions in the small
intestine (Meckel's diverticulum), the colon (juvenile polyps, lymphonodular
hyperplasia, or inflammatory bowel disease [IBD]), anorectum (fissures), or
intestinal duplications occurring anywhere from the mouth to the anus. Premature
neonates must be suspected of having NEC. Malrotation, intussusception, and
Hirschsprung's disease were discussed previously.
Lower GI bleeding is manifest either by bright red blood per rectum, melena, or
hematochezia. Localization of bleeding to the lower intestinal tract begins with
exclusion of bleeding from the stomach or duodenum. This is achieved by
passing a nasogastric tube and observing bilious aspirate or blood-free lavage.
Premature infants with rectal bleeding must be evaluated for NEC, which occurs
in 1.0% to 7.7% of all patients admitted to the neonatal intensive care unit, and
has mortality rates as high as 40%. NEC is characterized by ileus, abdominal
distension, bilious vomiting, GI bleeding, or abdominal wall erythema. Findings
of NEC on plain abdominal radiographs include pneumatosis intestinalis,
pneumoperitoneum, or portal venous air. Initial medical management of NEC
includes nasogastric decompression, broad-spectrum antibiotics, fluid
resuscitation, blood and blood-product transfusion for correction of anemia and
coagulopathy, serial examination, and supine and left-lateral decubitus films of
the abdomen. Operation is indicated for clinical deterioration, evidence of
gangrene, or perforation.
Meckel's diverticuli are found in approximately 2% of the population and are the
most common source of significant lower GI bleeding in children. Patients who
develop bleeding are typically of preschool age (mean, 2 years). Bleeding results
from peptic ulceration of the ileal mucosa from hydrochloric acid secreted from
ectopic gastric mucosa within the diverticulum. Bleeding is typically painless and
may be intermittent or massive, requiring transfusion. A technetium-99m scan is
used to identify the heterotopic gastric tissue in the diverticulum and is 75% to
85% sensitive for Meckel's diverticulum presenting with bleeding. [18]
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Failure to identify ectopic gastric mucosa is associated with a 5% to 10% error

rate, and persistent bleeding should be followed by a repeat scan in stable
patients. Otherwise, colonoscopy or laparotomy should be performed.
Sources of bleeding in the colon are usually polyps. These usually result in low-
volume bleeding and are diagnosed with either barium enema or
colonoscopy. Lymphoid polyps are benign polyps resulting from lymphonodular
hyperplasia of the colon and occur most commonly in infants and preschool-
aged children. They are thought to occur in association with systemic illness,
and they resolve without treatment.
Juvenile polyps or retention polyps are benign hamartomatous lesions that may
be found throughout the gastrointestinal tract (typically proximal to the
transverse colon) in children but are uncommon in infants. They account for
more than 90% of polyps found in this age group, and more than half of affected
patients have multiple polyps. Bleeding occurs with sloughing of polyps,
typically occurs with bowel movements, is painless, and is rarely massive.
Multiple juvenile polyposis is managed expectantly (colonoscopic polypectomy
or transanal excision) and usually resolves by adolescence; however, precise
histology of excised polyps is important because multiple juvenile polyposis may
be confused with multiple adenomatous polyp syndromes (e.g., Gardner's
syndrome or familial polyposis), which have malignant potential.
Alimentary tract duplications may occur anywhere from the mouth to the anus.
Duplications are cystic or tubular structures typically lined by normal
gastrointestinal mucosa and lie in a mesenteric location in proximity to the
alimentary tube. They frequently share a common muscular wall and blood
supply with the normal bowel. They may present with pain, nausea, vomiting,
obstipation, or bleeding. Complications of duplications include obstruction,
volvulus, intussusception, peptic ulceration, perforation, and bleeding. Bleeding
may be sudden and massive, mimicking that seen with Meckel's diverticulum, or
may be mild and chronic, resulting in anemia. The diagnosis of an enteral
duplication may be suspected in patients with acute or chronic blood loss,
abdominal pain, and radiologic findings (i.e., plain films, computed tomography
[CT], magnetic resonance [MR] imaging, sonography) of a mass connected to or
displacing a segment of the GI tract, or on radioisotope scans demonstrating
ectopic gastric mucosa in gastric duplications. The treatment for gastrointestinal
duplications is surgical.
Anorectal bleeding is characterized by bright red blood on the outside of the

stool. It usually results from anal fissures. Constipation may develop and may
result in large, bulky stools that cause a tear typically in the posterior midline.
Fissures are treated with stool softeners and warm sitz baths. Excision is rarely
necessary. Fissures in older children must alert the physician to the possibility of
inflammatory bowel disease, specifically, Crohn's disease.
With 25% of all new cases occurring in patients younger than 25 years of age,
IBD is an important diagnostic consideration for physicians caring for children.
Issues unique to the pediatric population with IBD include [61] :
IBD in infants and young children has an atypical course.
Malnutrition and growth failure are major concerns in

prepubertal children.
The life-long risk of malignant transformation is increased with IBD

(ulcerative colitis) presenting in childhood.
Chronic disease may have profound implications in the emotional

development of adolescents.
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Differing management strategies and long-term implications make it imperative

for accurate diagnosis of either Crohn's disease or ulcerative colitis in pediatric
patients with IBD.
Most cases of ulcerative colitis are diagnosed between 15 and 30 years of age
(4% present before 10 years of age), and reports of ulcerative colitis presenting in
infancy have been made. [25] [29] [112] Most children present with acute bloody
diarrhea. This is usually accompanied by cramping and tenesmus. Extraintestinal
manifestations may include arthralgia (25%, most commonly involving the
knees, ankles, and wrists), skin lesions (e.g., erythema nodosum and pyoderma
granulosum), liver disease (15%, caused by fatty infiltration or sclerosing
cholangitis), uveitis (2%), osteoporosis, oral ulceration, and growth
retardation. [33]
Clinical presentation may include growth retardation; pallor (anemia from

chronic blood loss); and, in acute cases, fever, dehydration, and abdominal pain,
particularly in the region overlying the sigmoid colon. Severe abdominal
distension in patients presenting with fever and seemingly in septic shock should
raise the suspicion of toxic megacolon.
Diagnosis is best made by colonoscopy and biopsy; the rectum is involved in

more than 95% of cases. The characteristic histologic findings of ulcerative
colitis are crypt abscesses and mucosal bridging, or "skip lesions."
Although medical therapy may be used in acute exacerbations of ulcerative

colitis, the curative treatment is total colectomy with removal of the diseased
rectum. End-ileostomy or, ideally, ileoanal pull-through, are typically performed.
This not only cures patients of ulcerative colitis but also prevents the risk for
malignant degeneration, which is reported in 3% of patients in the first decade of
disease and 20% of patients each subsequent decade. [33]
Crohn's disease was originally described as an inflammatory condition of the

bowel (regional ileitis) by Crohn, Ginzburg, and Oppenheimer in
1932. [23] Crohn's disease is being recognized with increasing frequency
in children. In the Mayo Clinic's review of more than 600 cases, 14% of patients
presented before the age of 15 years. [124]
Children may present with weight loss (90%), abdominal pain (70%), diarrhea
(67%), or fever (25%). [33] Bloody diarrhea is also a common presentation. The
clinical course of patients with Crohn's disease seems to be more constant than
the relapsing course of ulcerative colitis. Perianal ulceration also distinguishes
Crohn's disease from ulcerative colitis. Extraintestinal manifestations of Crohn's
disease are similar to those of ulcerative colitis.
Pathologically, Crohn's disease is distinguished by "creeping fat" (along the

serosal surface from the mesentery), deep fissures, and a cobblestone appearance
in the mucosa. Ulcerations penetrate deeply through the muscularis and may
result in fistulas, sinus tracts, and abscess formations. Histologically,
multinucleated giant cells and granulomas may be found in the submucosa,
muscularis, and regional lymph nodes.
On presentation, right-sided lower quadrant pain is commonly associated with a

"mass" that represents an inflamed, edematous terminal ileum. Children with
colorectal Crohn's disease might have perianal ulcers. Diagnosis is confirmed by
endoscopic biopsy and demonstration of the aforementioned histologic findings.
Because Crohn's disease cannot be cured by surgical resection, most children are
managed medically, with surgical intervention reserved for patients with
complications of the disease (e.g., obstruction, abscess, perianal or enteroenteric
or enterocutaneous fistula, perianal ulcer or abscess, or severe hemorrhage).
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ABDOMINAL MASSES
Abdominal tumors most commonly present in infants or children as an
asymptomatic mass, typically noted by the parent during bathing or physician on
routine examination. The following discussion emphasizes the clinical
characteristics, presentation, and evaluation of patients presenting with the more
common abdominal tumors seen in infants and children: neuroblastoma, Wilms'
tumor, and hepatic neoplasms.
Neuroblastoma
In the United States, neuroblastoma is the most common tumor in children less
than 1 year of age. Unlike other solid abdominal tumors in children (e.g., Wilms'
tumor and rhabdomyosarcoma), the biologic characteristics of neuroblastomas
are less well defined, and therapy is less effective.
History
Virchow [126] first described these tumors in 1864. The

term neuroblastoma, designating its cellular origin, was coined by Wright [128] in
1910. Neuroblastoma was first described by early investigators as
"sympathicoblastoma," "sarcoma of the adrenal gland," and "neuroblastoma
sympatheticum." [69] In 1939, Farber [31] described a series of 301 malignant
tumors studied at Boston Children's Hospital over a 10-year period. Forty of
these tumors were neuroblastomas, of which 32 occurred in the abdomen. Thirty
Wilms' tumors were also described as "embryomas" of the kidney. These cases
were followed, and later reports described their limited curability.
Etiology and Pathology
This disease is a family of tumors that pathologically includes neuroblastoma,

ganglioneuroblastoma, and ganglioneuroma. This spectrum of pathology goes
from very malignant (i.e., neuroblastoma, unfavorable histology) to completely
benign (i.e., ganglioneuroma), with all of these tumors originating from the same
cell line (i.e., primordial neural crest cells found in the sympathetic ganglia and
adrenals). The variability of differentiation, tumor location, and hormonal
activity (i.e., secretion of sympathomimetic peptides) accounts for the variety of
presenting signs and symptoms found with this disease. Much progress has been
made identifying biologic markers, hormone secretion types and frequency,
genetic patterns, and heritable components to help predict tumor activity;
however, age (< 1 or > 1 year) and stage (I, II, and IVS versus III and IV) are still
the most reliable predictors of cure and patient survival. [13] [42] [82]
Grossly, the tumor (Fig. 5) appears very vascular, friable, bloody, and necrotic
(in malignant neuroblastoma) to firm, fleshy, and nodular (postchemotherapy and
in mature ganglioneuromas). Microscopically, this tumor is one of the several
round, small, blue cell tumors seen in childhood. Therefore, it must be
differentiated from Ewing's sarcoma, primitive neuroectodermal tumors,
lymphomas, rhabdomyosarcomas, and others by the location of the primary
tumor, presentation, special staining techniques of biopsied material, and
presence or absence of hormonal activity.
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Figure 5. Neuroblastoma. Massive abdominal distension at the time of biopsy. This

3-month-old girl presented with abdominal distention and respiratory distress. The
liver, which was found to be totally infiltrated by tumor, is outlined. This Stage IVs
patient underwent biopsy and responded well to therapy. (Courtesy of Richard H. Pearl,
MD, Peoria, IL.)
The Shimada classification system, the most widely used pathologic predictor of
tumor activity, aids clinicians in the selection of therapy and correlates well with
outcome and survival. This method uses the organization of the stromal tissue
(rich or poor), cellular morphology, and the degree of differentiation in the
neuroblastic cells; correlating this information with patients' age to determine
favorable and unfavorable histologic groups. This method has been widely
accepted and is a well-established predictor of outcome in many studies. [13] [20]
Epidemiology
Neuroblastoma is the most common extracranial solid tumor in children.

Approximately 550 new cases are reported in the United States annually (8-10%
of all pediatric cancers), with a prevalence of 1 in 7000 to 10,000 live births and
an incidence of 8.0 to 8.7 cases per 1 million children less than 15 years old.
Ninety percent of cases occur before 8 years of age, and 50% occur in those less
than 2 years old, with a median age at diagnosis of 22 months. Neuroblastoma is
reported in slightly more boys than girls with the ratio being
1.2:1. [13] [44] Neuroblastomas have been observed in utero, and fetal hormonal
excretion has caused hypertension and flushing in the mothers of infants so
diagnosed. In addition, neuroblasts have been seen as incidental findings in
autopsies of infants less than 3 months of age in 1% of cases, suggesting that
cellular maturation occurs frequently without malignant change. Ninety percent
of prenatally diagnosed neuroblastomas are Stage I or IVs, with reported survival
in a series of 55 infants of more than 90% treated with surgery alone or
observation with spontaneous regression. [1]
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In Japan and Quebec, infant screening studies have revealed the presence of
neuroblastomas before clinical presentation. However, the ability of mass
screening to improve overall survival has yet to be proven. Reports of familial
neuroblastoma in twins, siblings, and consecutive generations and bilateral
disease suggests a hereditary component. Other ties to genetic, heritable, or
teratogenic causes for this disease can be seen in the syndromic connection with
Hirschsprung's disease, pheochromocytomas, neurofibromatosis, Beckwith-
Wiedemann syndrome, and maternal ingestion of alcohol or phenytoin. [9] [67] [82]
Clinical Presentation
History and Physical Findings
The presenting signs and symptoms vary with the site of the primary tumor,
presence or absence of local spread or distant metastases, and the degree of
hormonal activity. An intra-abdominal location of the primary tumor occurs in
50% to 70% of cases. Most of these are adrenal (two-thirds), with the remainder
in the sympathetic paraspinous ganglia. Approximately 20% of cases are in the
chest (posterior mediastinum), and less than 5% occur in the head, neck, and
pelvis.
Head and neck primaries can present with visual changes, exophthalmos, panda
eyes (i.e., bilateral black eyes), Horner's syndrome, (i.e., ptosis, meiosis, and
anhydrosis), and cerebellar ataxia. Thoracic tumors, particularly with dumbbell-
shaped extensions into the spinal canal, may cause neurologic or gait
disturbances, cough, or shortness of breath. Abdominal tumors are often
asymptomatic until quite large and then principally present with pressure effects
(e.g., vomiting, early satiety, and crampy abdominal pain). Tumors in the lower
pelvis can cause urinary frequency and incontinence and lower extremity
vascular changes may be reported. Bone pain represents distant metastatic
spread. In children with hormonal activity, catecholamine and vasoactive
intestinal polypeptide (VIP) release can cause weight loss, flushing, jitteriness,
hypertension, diarrhea, anemia, and sleep disturbances. In infants with Stage IVs
disease, hepatomegaly and subcutaneous masses can be appreciated. On physical
examination, the primary tumor (if palpable) is hard, firm, and fixed with an
irregular border. All of these signs and symptoms help differentiate
neuroblastoma from Wilms' tumor because the children with neuroblastoma
often present "sick," whereas those with Wilms' tumor are usually "well." [13] [67] [82]
Diagnostic Studies
Urinary excretion of catecholamine metabolites is the primary test for screening,

diagnosis, and monitoring the effects of therapy. Dopamine and norepinephrine
are metabolized and excreted as HVA and VMA, respectively. Random samples
frequently suffice, with 24-hour urine collection to quantitate absolute levels of
metabolic activity. Serum ferritin levels in advanced tumors and those with
unfavorable histology frequently are high (> 150 ng/mL). With response to
therapy, the level decreases and often returns to normal. Persistent elevations or
rising levels posttherapy are indicative of recurrent or aggressive disease and
suggest a poor prognosis. Neuron-specific enolase levels correlate with tumor
burden and stage of disease. Levels of more than 100 ng/mL correlate with
increased mortality and poor prognosis. Of note, in patients with Stage IVs
disease, even with extensive tumor burdens, both serum ferritin and
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neuron-specific enolase levels are normal, suggesting a direct correlation to

unfavorable histology and elevation of these markers. Bone marrow aspiration
biopsies can be diagnostic for neuroblastoma, and open or radiologic-guided
biopsies of the primary tumor can, in certain clinical settings, be avoided. Lactate
dehydrogenase (LDH) elevations are seen frequently in patients with large tumor
burdens or advanced disease. Although LDH is not a specific marker for
neuroblastoma, in patients known to have the disease, levels of more than 1500
mug/mL have significant independent predictive value.
Genetic Markers and Molecular Biology
The biologic markers present in neuroblastoma cells provide hints into the
genetic characteristics that predict high-grade versus low-grade tumors. N-myc
amplification is seen in patients with rapid tumor growth and advanced disease
predictive of a poor outcome. This is independent of age or stage with the
exception of certain Stage I and IVs patients. Deletion of the short arm of
chromosome 1, known as 1p deletion, is also frequently associated with high-
grade, poor prognosis tumors. Some cases with 1p deletion are seen without N-
myc amplification; however, virtually all cases with N-myc amplification have
deletion at the 1p locus. Tumor ploidy, interestingly, is the reverse of what would
be expected, with lower-stage tumors being triploid (or higher) and less-
advanced tumors being diploid. This evaluation is done by flow cytometry.
Radiologic Evaluation
Magnetic resonance imaging is the most useful imaging examination because full
detail of the primary tumor, extension (if present) into the spinal canal, and the
relationship of the tumor to blood vessels and other visceral organs all can be
appreciated. CT scans provide similar detail to MR images; however, contrast
enhancement is required, the relationship to blood vessels is not imaged as
discretely, and the children are exposed to radiation (albeit a small dose).
However, with the multiple radiologic examinations these children receive over
a sustained period of time, this should be considered. Chest radiographs
frequently reveal thoracic primaries (> 50%), but are not sufficiently sensitive to
evaluate for metastatic lung involvement and should not be routinely ordered for
this purpose.
Metaiodobenzylguanidine scintigraphy (MIBG) is very accurate for evaluating

neuroblastoma and is excellent for establishing bone or bone marrow
involvement. Primary, metastatic, and recurrent disease can also be imaged but
without discrete anatomic detail. A recent report documents the assistance in
localizing tumor spread with the use of intraoperative MIBG scanning. This
modality was helpful in 65% of 58 children so treated. [76]
Staging
Three systems are used for staging this disease, which adds to the confusion and
difficulty in evaluating the results in the literature. These are: The Evans
classification used by the Children's Cancer Study Group, the Pediatric Oncology
Group (POG) system, and the International System for Staging Neuroblastoma
(INSS). The details of these three systems are not germane to this discussion,
except to note that over time and with modifications, the INSS system will
probably become the standard. All three systems describe good and poor
prognostic
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groups, and all have a special category for those under 1 year of age with hepatic
and skin involvement who routinely do very well (Stage IVs).
Treatment
The foundation of therapy for this disease is multimodal and is based on stage,
age, tumor size, presence or absence of metastatic spread, and favorable versus
unfavorable prognostic groups. Therapy can range from surgery alone (Stage I);
to surgery with postoperative chemotherapy (Stage II); to induction
chemotherapy, radiation therapy, and surgery with follow-up chemotherapy or
radiation therapy (Stage III), to higher-dose chemotherapy, radiation with bone
marrow ablation, and bone marrow transplantation, with or without surgery
(Stage IV). This description is very simplistic and fails to capture the enormous
variation in the selection of therapy that is required in each case; however, it will
let the reader appreciate the intensity and variability of therapy that has allowed
for the gradual improvement in outcome for those with high-stage, unfavorable
histologic tumors. Immunotherapy, adoptive immunotherapy, and gene therapy
are in phase I and II trials and are not yet available as standard therapy. Early
reports of boosted dose radiation treatment using intraoperative therapy (IORT)
are promising in patients with Stage III or IV cancer but have yet to be fully
tested. [71]
The extent and timing of the initial surgery has come into question in many
studies. Shamberger and co-workers from POG, in a report covering
349 children having a surgical resection for an intra-abdominal primary during a
10-year period, documented a 25% incidence of nephrectomy in those operated
on before chemotherapy and a less than 10% nephrectomy rate in those
pretreated before surgery. [107] In another report, patients with Stage III or IV
cancer with microscopic residual disease after resection were treated with IORT
and postoperative chemotherapy and had disease-free survival better than would
have been expected from more radical surgery [60] ; however, the opposite was
documented in another POG study on children with Stage IIb or III cancer with
biologically favorable tumors demonstrating improved event and disease-free
survival with complete initial resection over those resected in the unfavorable
category. When analyzing those with favorable histology, however, only the
impact of aggressive surgery within this group was described as "unclear."
It is well accepted that the real improvement in survival in neuroblastoma has

occurred with the more sophisticated and aggressive use of chemotherapy (with
or without radiation therapy and bone marrow transplantation), with surgery
playing a primary role in Stage I only.
Complications, Prognosis, and Outcomes

Depending on the type and intensity of therapy selected, every conceivable
complication can occur. In patients subjected to the most rigorous treatment
regimens (Stages III and IV refractory or relapse with high-dose chemotherapy
rescue with or without bone marrow transplantation), complications occur in
100% of patients. Although advanced disease with unchecked spread can be
fatal, at times, complications from therapy, not the disease itself, are the cause of
death. Having said this, however, this aggressive approach has allowed for
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survival of patients with advanced disease in 30% to 40% of cases, whereas

previous survival rates of less than 10% were the norm.
It is very difficult to report accurate and current outcome data for this disease
because the protocol treatments constantly are revised, improved, and changed;
however, "ball-park" figures for general use are: Stage I, 100%; Stage II, 80%;
Stage III, 40%; Stage IV, 10%; and Stage IVs, 80%. These results do not factor
in age, N-Myc, ploidy, LDH, and other predictors that affect outcome within
each stage. When looking at age alone as a predictor of outcome, approximately
75% of those less than 1 year of age will survive, whereas 70% of the older
cohort die. Specific results of selected patient groups undergoing protocol
evaluation in multicenter trials differ from the data provided here; however, with
advanced disease in children older than 1 year, having very little improvement in
survival during the past three decades, more elegant therapy focusing on genetic
manipulation or adoptive immunotherapy is required.
WILMS' TUMOR
History
Historically, Wilms' tumors have been termed embryomas, mixed

tumors, and nephroblastomas. In 1899, the term Wilms' tumor became the
popular nomenclature for these tumors of renal origin following the German
surgeon Wilms' publication of his monograph entitled Mixed Tumors of the
Kidney.

In 1972, Knudson and Strong [65] proposed a two-staged mutational model
suggesting that Wilms' tumor could occur in either hereditary or sporadic forms.
Certain known genes (suppressor genes), when deleted from the short-arm of
chromosome 11, are associated with Wilms' tumor.
Tumors are typically large, well-encapsulated masses. Histologically, the tumors

may be predominantly blastemal, stromal, epithelial, or a mixture of these three
cell types.
Epidemiology
Wilm's tumor is both the most common abdominal malignancy and the most
common renal malignancy in childhood. The incidence is 1 in 15,000 live births,
with 500 new cases reported in the United States each year. [19] The male-to-
female ratio demonstrates a small but statistically significant female
preponderance (1.0:1.1). [11] Incidence rates seem to be slightly elevated for US
and African blacks compared with whites but are only half as great among
Asians. Results of studies from the National Wilms' Tumor Study Group
(NWTS) indicate an incidence of bilaterality of 6% to 7%. [11] Bilateral Wilms'
tumors are associated with a higher occurrence in females (male-to-female ratio,
1:2), a younger age at diagnosis than patients with unilateral tumors (25 versus
44 mo), and a higher incidence of associated genitourinary anomalies. Familial
Wilms' tumor has been reported (1% of all cases) and is suspected to have an
autosomal dominant mode of inheritance with incomplete penetrance. [43] [55]
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A number of congenital anomalies have been reported in association with Wilms'

tumor. Patients with aniridia, cryptorchism/hypospadias, Beckwith-Wiedemann
syndrome, or intralobar nephrogenic rests, who also have Wilms' tumor, tend to
be younger than the average patient (median, 17-27 mo) when diagnosed.
Aniridia, a rare hereditary condition of absence (usually bilateral) of the iris, is

associated with a risk for Wilms' tumor that is 600 times that of the general
population. [89] Because of the high risk for Wilms' tumor, patients with aniridia
are recommended to have a physical examination, urinalysis, and abdominal
sonogram every 3 months until 4 years of age. [86]
The incidence of hemihypertrophy in the general population is 1 in 30,000. The

risk for hemihypertrophy is increased 1000-fold in patients with Wilms'
tumor. [11] Patients with Wilms' tumor and hemihypertrophy are more likely to be
female (60%) and more commonly have bilateral tumors (16%). [63]
A 4% to 5% increase in cryptorchidism and hypospadias has been reported in

boys with Wilms' tumor by the NWTS. Bilateral Wilms' tumors are more
common (23%) in patients with these genitourinary anomalies. [11]
WAGR syndrome (Wilms' tumor, aniridia, genitourinary malformations, and

mental retardation), and Drash's syndrome (male infants with
pseudohermaphroditism, Wilms' tumor, mental retardation, and degenerative
renal disease) occur rarely. Children with Beckwith-Weidemann syndrome have
a higher incidence (6-10%) of abdominal tumors, including hepatoblastoma,
adrenal cortical carcinoma, and Wilms' tumor. [63] Although regular, surveillance
ultrasound examinations of infants with Beckwith-Weidemann syndrome has
been suggested and used, [106] its usefulness has not been proven. [22]
History
Wilms' tumor typically presents in otherwise healthy, thriving preschoolers. An

asymptomatic mass may have been noted by the parent during bathing or on
routine examination in the pediatrician's office. Pain is a rare finding and, when
present, usually indicates a degree of tumor necrosis and subcapsular or
parenchymal bleeding. Less commonly, patients may have hypertension or
microhematuria. In children presenting with an acute abdomen and Wilms'
tumor, free rupture or hemorrhage into the peritoneal cavity must be suspected.
Physical Examination
Extra-abdominal examination may reveal fever, occurring as a result of tumor

necrosis, and hypertension. Manifestations of intravascular extension include
hepatosplenomegaly, ascites, caput medusae, cardiac murmur, or evidence of
gonadal metastases. A varicocele in a boy with a left-sided tumor indicates renal
vein occlusion. On abdominal examination, a large, firm mass that is nontender
and only slightly mobile is palpated.
Diagnostic Studies
Extensive bloodwork is not necessary in the diagnosis of Wilms' tumor. Based on

clinical presentation alone, after the diagnosis is suspected, confirmation
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Figure 6. Wilms' Tumor. A 3-year-old girl was diagnosed with Stage V (bilateral)
Wilms' tumor during evaluation of fever by her pediatrician. The abdominal
enlargement was slow growing and not appreciated by the parents. This CT scan
reveals the right kidney to be totally replaced by tumor. In contrast to the left kidney, which
had excretory function, there is no contrast dye enhancement of the right kidney. The
patient's preoperative BUN and creatinine were 7 and 0.8 respectively. The patient is
currently on protocol in National Wilms' Tumor Studys (NWTS 5). (Courtesy of Richard
H. Pearl, MD, Peoria, IL.)
is completed radiographically. Caty and Shamberger suggest three objectives in

[19]
the diagnostic evaluation of children with suspected Wilms' tumor:

To confirm the tumor's location of origin to the kidney and distinguish it
from other abdominal masses, such as neuroblastoma or hepatic tumor
To evaluate the resectability of the tumor, specifically, to identify local

tumor invasion and renal vein involvement by the tumor
To evaluate for metastatic or bilateral disease
Initial evaluation may begin with abdominal sonography or CT scan (Fig. 6) ,

which will establish the kidney as the organ of origin and whether inferior vena
cava or renal vein extension is present. MR imaging further delineates tumor
extent and vascular invasion and identifies contralateral renal involvement. CT of
the chest is also recommended to rule out lung metastases. [19]
Staging
The NWTS studies (I to V), first started in 1969, have allowed for great strides in
the treatment of this disease. In addition, because all major children's cancer
therapy groups have collaborated in these studies, a common staging system has
evolved that allows for excellent study control, evaluation, and comparison of
outcomes.
The current staging system in use for NWTS IV and V is:
Stage I: Tumor limited to kidney and completely excised (no spill, no

residual)
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Stage II: Tumor extends beyond kidney but completely excised (local
spill, tumor thrombus, perirenal soft tissue)
Stage III: Nonhematogenous spread confined to abdomen (lymph nodes,

diffuse peritoneal contamination, peritoneal implants, grossly involved
resected margins, or invades nonresectable vital structures)
Stage IV: Hematogenous spread beyond Stage III (e.g., lung, liver, bone,
or brain)
Stage V: Bilateral renal tumors
Included in the differential diagnosis of abdominal masses in children are

Wilms' tumor, neuroblastoma, hepatic tumors, Burkitt's lymphoma,
rhabdomyosarcoma, pheochromocytoma, and benign renal cystic masses.
Treatment
The treatment of Wilms' tumor is based on complete surgical excision (when

possible), with follow-up chemotherapy, radiation therapy, or both. NWTS IV
compared conventional therapy with pulse-intensive chemotherapy administered
over different time courses. A principal question was economic. That is, can a
shorter, more intensive course of chemotherapy be as good (or better), with less
cost, fewer complications, and less intrusion on family life? The results showed
that pulse-intensive therapy was less toxic and had equally excellent relapse-free
survival as more costly and timely conventional therapy. [103] In NWTS V, this
pulse-intensive therapy is now used, and a new question to be analyzed is the role
of chemotherapy in Stage I Wilms' tumor. In this most recent study, all Stage I
tumors weighing less than 550 g in children less than 24 months old will be
treated with surgery only. The purpose of this question is to see whether the
complications of follow-up chemotherapy can be avoided in what may be a
completely curable lesion by surgery alone.
The other question in NWTS V deals with chemotherapy intensity and length in
relation to stage and histologic criteria (favorable versus unfavorable) with
postoperative radiation reserved for Stage III and IV tumors only. [103]
Outcome
The results of NWTS IV are based on histology, stage, and standard versus
pulse-intensive therapy. In this study, 1687 children less than 16 years of age
were treated. Low-risk (LR) patients included Stage I and II with favorable
histology and Stage I anaplastic. The high-risk (HR) group included Stage III and
IV with favorable histology or Stage I to IV with clear cell sarcoma. The LR and
HR groups were randomized to the same chemotherapy regimens delivered in
standard versus pulse-intensive modes. The results demonstrated no difference in
2-year relapse-free survival (LR, 91.3% versus 91.4%; HR, 87.3% versus 90.0%)
in the two study groups. These data allowed for the pulse-intensive regimen to
become the standard in NWTS V. [39] Further analysis of subgroups has allowed
for further refinements in therapy. As previously alluded to, the 4-year relapse-
free and overall survival for Stage I patients less than 2 years of
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age with tumors less than 550 g over the past 20 years were: NWTS I, 89.1%;
NWTS II, 96%; and NWTS III, 93.2%. There was no evidence in these three
[38]
studies that this survival had improved over time. In addition, the relapse-free
survival for the same age and stage patients, but with tumor more than 550 g was
much poorer ( p < 0.02). These data, further refined in NWTS IV, allowed for the
surgery-only trial for this selected group of patients in NWTS V.
The results of those with Stage V Wilms' tumor (bilateral renal involvement)
were reviewed in two recent reports. The first study reviewed 185 patients over
22 years with overall survival of 83%, 73%, and 70% at 2, 5, and 10 years,
respectively. Survival was not affected by the use of preoperative chemotherapy.
In addition, surgery that conserved renal tissue did not compromise survival,
while maintaining renal function. [80] The second study reviewed 98 Stage V
patients undergoing renal salvage procedures (partial nephrectomy and
enucleation) in NWTS IV. Local tumor recurrence in the remnant kidney bed
was 8.2%, with 4-year survival of 81.7%. These data reveal the efficacy and
safety of this mode of therapy. [54]
In those with tumors judged initially to be inoperable, preoperative chemotherapy

after biopsy was performed on 103 patients, reported in NWTS III. With tumor
shrinkage in most patients, 93% were able to undergo complete nephrectomy
after this pretreatment. Eight children failed to respond to therapy and died
without surgery. Overall, 4-year survival was 74%, which compares very
favorably to the 88% survival in those who were deemed resectable at initial
evaluation. [100]
Complications
Patients treated for Wilms' tumor have all the standard complications of any
patient receiving multimodal aggressive therapy (e.g., infections, bleeding, and
dehiscence). Two specific complications, however, are the subject of two
interesting reports. The first focuses on the incidence, causes, and risks of small
bowel obstruction after nephrectomy for Wilms' tumor. In NWTS III,
131 children of 1910 having nephrectomies developed a small bowel obstruction
(6.9%). The cause was adhesions in 104, intussusception in 17, internal hernia in
8, and unclear in 8. Four children died from this complication. Factors
influencing the incidence of small bowel obstruction were stage at resection,
extra-renal involvement, and en bloc resection of other organs. Postoperative
radiation therapy did not increase the incidence of small bowel
obstruction. [99] The second report reviews 5278 children enrolled in NWTS from
1969 to 1991 and documents a second malignant neoplasm occurring in 43
patients (with only 5.1 expected). Fifteen years' post-therapy, the cumulative
incidence of second malignant neoplasm was 1.6% and increasing. These data
suggest the importance of detailed and thorough lifelong follow-up for all of
these patients. [12]
Clinical Commentary
The data in this Wilms' section are easy to summarize, review, and evaluate
because of the series of excellent reports conducted under the auspices of the
NWTS organization since 1969. The sections on neuroblastoma and liver tumors
reveal the difficulty in evaluating and comparing similar data when different
staging and treatment protocols are used. As the major pediatric cancer treatment
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TABLE 2 -- EPIDEMIOLOGY, APPEARANCE, DIAGNOSIS, AND TREATMENT OF
BENIGN HEPATIC TUMORS IN CHILDREN
Epidemiol Appearanc
Type ogy e Diagnosis Treatment Outcome
Simple Cysts Congenital 10% RUQ mass Simple Recurrenc
; 3F:1M; multiloculat seen on US or excision or e unlikely
whites > ed; inferior CT; can be unroof and
blacks aspect R seen in utero drain into
lobe; clear, peritoneum
fluid-filled
Polycystic Cysts Inherited; Extensive US or CT None; If severe
50% fluid-filled reveals advanced hepatic
concordan cysts multiple cysts disease liver failure
ce with throughout throughout the transplant
polycystic liver liver
kidney
disease
Adenoma Rare, Solitary 50% have Wedge Excellent,
benign; > mass; more abdominal resection or recurrenc
in teenage frequent in pain; 25% lobectomy e rare; not
girls; right lobe have bleeding; premalign
related to cold spot on ant
oral isotope scan;
contracepti CT most
ve use and useful; large
glycogen feeding vessel
storage on MR
disease angiography
Focal nodular May occur Very Asymptomatic Biopsy or Benign
hyperplasia in response vascular; ; rarely wedge course
to injury large venous bleeds; resection;
and system; observation if
US solid
regeneratio grossly asymptomatic
mass;
n resembles
hepatoblasto MRI/CT s
ma, stellate olid mass with
central scar central scar;
nuclear
medicine
scan isode
nse
TABLE 2 -- EPIDEMIOLOGY, APPEARANCE, DIAGNOSIS, AND TREATMENT OF
BENIGN HEPATIC TUMORS IN CHILDREN
Epidemiol Appearanc
Type ogy e Diagnosis Treatment Outcome
Mesenchymal Etiology is Large, 80% Will require Benign,
hamartoma unknown multicystic diagnosed < 1 biopsy to in the
benign year old, differentiate absence
mass; has from other of CHF
vascular
all the cell solid lesions;
may
types and excision or
components bleed may internal
of normal cause CHF; drainage if
liver tissue mass on CT or large cyst
(histology MRI predominates
diagnostic)
Vascular lesions: Most Large, Frequently May be Benign,
cavernous common usually in asymptomatic; observed in the
hemangiomas benign right lobe; can cause particularly if absence
lesion, 2nd AV CHF if large; small or of CHF
most shunting rupture or asymptomatic;
common common bleeding spontaneous
liver uncommon; resolution
tumor, MR common;
may occur angiogram resection or
with will reveal embolization
cutaneous large feeding as needed
hemangio vessel; MRI,
mas CT, US all
useful
Infantile Diagnosed Occurs High-output If CHF
Small obs
hemangioendothe in infancy throughout CHF not
erve;
lioma the liver; common; rapidly
symptoms; Rx
hepatomega cutaneous controlled
with digitalis,
ly; large hemangiomas; medically
diuretics,
vascular thrombocytop or
prednisone; if
channels; enia; bruits surgically
symptoms
thrombosis (this , death
progress:
and combination can occur
hepatic artery
calcification is virtually
embolization
seen diagnostic)
or resection
F, female; M, male; R, right; RUQ, right upper quadrant; US, sonography; CT, computed
tomography; MRI, magnetic resonance imaging; CHF, congestive heart failure; AV,
arteriovenous.
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groups agree to increased collaboration, our ability to effectively treat and

evaluate childhood cancers will improve.
LIVER TUMORS
History
In Surgery of Infancy and Childhood by Gross, [41] only 2.5 pages are devoted to a
cursory discussion of liver tumors. At the time of publication (1953), the Boston
Children's Hospital experience with hepatic neoplasms was 18 patients, 11 of
whom had malignancies, resulting in 2 survivors. At the time liver resections
were rare, transfusion therapy was in its infancy, chemotherapy was not available
for these tumors, and intensive care facilities did not exist. Over the next four and
a half decades, advancements in these areas, discussed in the following pages,
would change the survival in liver cancer in children.
General Discussion
Approximately two thirds of all liver neoplasms are malignant. The distribution
of benign and malignant neoplasms, as described by Greenberg and Filler, [40] was
derived from a compilation of four major series documenting the disease
distribution in North America and is summarized in Table 2 .
To simplify this discussion, all the information concerning benign liver tumors is
summarized in Table 2 to include epidemiology, appearance, diagnosis,
treatment, and outcome. A full analysis of malignant neoplasms comprises the
remainder of this section.
Hepatoblastoma (Fig. 7) is usually solid, arising from the right lobe of the liver
(60-70%). Grossly, it is a lobulated, bulging mass, usually quite large at initial
presentation, with a pseudocapsule and areas of necrosis. Histologically,
epithelial and mixed epithelial and mesenchymal cell types are described, with
the epithelial component comprising fetal and embryonal subsets or a
combination of the two. [120] Hepatocellular carcinoma is pathologically the same
disease as seen in adults, absent the frequent association with cirrhosis. Necrosis
and hemorrhage are more common with hepatocellular carcinoma than with
hepatoblastoma. Histologically, the cells resemble larger-than-normal
hepatocytes with a polygonal shape and single nuclei. The fibrolamellar
pathologic variant seen in older children conveys a survival advantage.
In a large series comparing 168 cases of hepatoblastoma with 28 cases of

hepatocellular carcinoma, no statistically significant difference in outcome was
noted except for those with the fetal subtype of epithelial tumor with a 92% 2-
year survival compared with a 57% survival for all others. [120]
Epidemiology and Genetics
A genetic association with the Beckwith-Wiedemann syndrome and

hemihypertrophy has occurred in 2% of patients. [114] Simultaneous cases of
hepatoblastoma
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Figure 7. Hepatoblastoma. Intraoperative view of the liver of a 13-month-old girl

with hepatoblastoma. The tumor was initially unresectable due to tumor extension
into both hepatic lobes with no resection margin clear of the right and left portal
structures. After treatment with vincristine and Adriamycin the tumor volume decreased
substantially. Note the white and firm appearance of the tumor and markedly decreased
vascularity after treatment. A left hepatic lobectomy rendered this patient disease-free and
she is a long-term survivor. (Courtesy of Richard H. Pearl, MD, Peoria, IL.)
and Wilms' tumor have been described, as has familial

[35]
clustering. Hepatoblastoma has also been associated with maternal oral

[116]
contraceptive use and alcohol ingestion. In families with familial

[62] [79]
adenomatous polyposis, there is an increased incidence of hepatoblastoma.

Likewise, increased polyposis occurs in those who survive treatment for
hepatoblastoma. In hepatocellular carcinoma, a strong association with a
[56]
previous (or chronic) hepatitis B viral infection is known. [85]
Hepatic malignancies are the tenth most common pediatric cancer, with an
annual incidence of 1.6 cases per 1 million children (0.9 hepatoblastoma and 0.7
hepatocellular carcinoma). In hepatoblastoma the median age at diagnosis is 1
year, and in hepatocellular carcinoma, it is 12 years. The male-to-female ratio in
hepatoblastoma and hepatocellular carcinoma is 1:7:1 and 1:4:1, respectively. [40]
History and Physical Findings
Hepatoblastoma is diagnosed, usually before the age of 2 years, as an

asymptomatic mass, appreciated incidentally while the child is bathed by the
parent or on routine physical examination by the physician. Abdominal
enlargement with an obvious tumor, causing systemic symptoms from a mass
effect (e.g., weight loss, anorexia, nausea, vomiting, or pain) is less common.
Infrequently, hemihypertrophy, jaundice, or precocious puberty is seen.
Precocious puberty is observed in the small group of children who secrete beta-
human chorionic gonadotropin (HCG). Osteopenia is present in approximately
25% of patients and resolves with therapy.
Hepatocellular carcinoma presents in older children and is often symptomatic
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with pain, nausea, vomiting, and weight loss common. In addition, signs and
symptoms of cirrhosis can occur with jaundice and splenomegaly. Initial
presentation with an acute rupture of the tumor and hemorrhage is reported. In
those with the fibrolamellar variant, the onset of symptoms is more gradual and
less severe, and these patients are usually older.
Diagnostic Studies
In both hepatoblastoma and hepatocellular carcinoma, mild anemia and elevation

of liver function tests can occur; however, these are nonspecific findings.
Elevation of alpha-fetoprotein (AFP) occurs in patients with hepatoblastoma
(90%) and hepatocellular carcinoma (50%). This protein, with a half-life of 5 to 7
days, reaches its maximum level during the second trimester in utero. After birth,
AFP levels progressively decrease, reaching adult baseline values of less than 15
ng/mL by 1 year of age. Markedly elevated levels (> 103 ng/mL) occur with these
tumors. In those receiving treatment for hepatoblastoma, the timing and
magnitude of AFP decline during treatment is a strong predictor of outcome.
Logarithmic declines in AFP levels are seen in responders to therapy. In patients
being treated for initially unresectable or metastatic hepatoblastoma, a large,
early response to therapy before a second operation (> 2 log fall in AFP) was the
strongest independent predictor of survival ( p < 0.0001). [125] Complete response
to therapy results in normal AFP levels, with recrudescence of secretion of AFP
heralding recurrence. Other laboratory tests of value are vitamin B12 binding
protein in hepatocellular carcinoma, hepatitis B surface antigen in older children,
and beta-HCG in those with precocious puberty.
For patients with suspected hepatic tumors, the initial imaging study is usually
sonography. In patients with hepatoblastoma or hepatocellular carcinoma, a large
mass is noted, with distortion of the hepatic vascular anatomy often seen. Details
of tumor involvement with other organs, extrahepatic blood vessels, or lymph
node spread require CT or MR imaging evaluation. Critical preoperative
decisions concerning resectability favor the use of MR imaging to determine
vascular and periportal involvement. CT scanning for the presence or absence of
lung metastases is required.
Staging
As with the other tumors mentioned in this article, several staging systems are
currently in use. Familiarity with the system used in any particular study allows
for comparison of various therapies. Some staging systems are done using
preoperative imaging studies (SIOP), whereas others require operative staging.
With induction chemotherapy becoming the norm, systems not dependent on
operative evaluation will become the standard.
Although not mentioned previously, the large abdominal mass in an infant,

particularly right sided, can present some diagnostic challenges. Both by physical
examination and evaluation by sonography and CT, it is not always possible to
differentiate a benign hepatic mass, hepatoblastoma, neuroblastoma, or Wilms'
tumor. In this situation, adjunctive laboratory tests (e.g., AFP, beta-HCG,
homovanillic acid [HVA], vanillymandelic acid [VMA], and neuron-specific
enolase)
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help establish the diagnosis. Even at open biopsy and resection, errors in
judgment have been made concerning these neoplasms. In centers where
preoperative chemotherapy is routinely given for all three tumors, percutaneous
needle biopsy can be used to establish the diagnosis and direct initial
therapy. Open biopsy is reserved for requirements of protocol therapy only.
[40]
Treatment, Prognosis, Complications, and Outcome
Without complete surgical resection, neither hepatoblastoma nor hepatocellular

carcinoma can be cured. Before effective preoperative chemotherapy,
unresectability or misadventures in the operating room in heroic attempts to
attain surgical cures yielded poor survival with significant morbidity. Over the
past decade, a series of reports from the Hospital for Sick Children in Toronto
have proven the efficacy of induction chemotherapy for hepatoblastoma with
cisplatin and doxorubicin. [32] [88] In their most recent report, they summarize a
series of 25 patients. Of these, 22 were entered in the protocol, with 20
responding to therapy (91%). Twenty had hepatic resections, and the other two
patients had total hepatectomies followed by liver transplantation. Nineteen of
the 22 patients are alive without disease (87%). Twelve children, eight deemed
initially unresectable before chemotherapy, are alive with more than 5 years of
follow-up. [28] They also report smaller resection, decreased blood loss, and
reduced morbidity with this regimen, with one intraoperative death and three
postoperative complications noted. Other centers have also reported similar
results with this preoperative chemotherapy regimen. [64] [98] [104] These data suggest
that the optimal therapy for this disease is radiologic staging, needle biopsy for
diagnosis, induction chemotherapy, followed by surgery with curative intent
(resection in most and transplant in the remainder).
The results in patients with hepatocellular carcinoma are not as promising, with
dependence on a surgical cure still the norm; however, trials of induction
chemotherapy are ongoing, and a similar approach may evolve over time.
RECURRENT ABDOMINAL PAIN
Recurrent, unexplained abdominal pain can be an extremely challenging, time-

consuming, and frustrating problem for pediatric surgeons, primary care
physicians, and families.
Definition, Epidemiology, and Incidence
Recurrent abdominal pain syndrome (RAPS) in children was originally defined

by Apley [3] and Apley and Naish [4] as abdominal pain, paroxysmal in nature,
occurring monthly over a period of at least 3 consecutive months, with enough
severity to result in a change in activity. The term chronic is often misused when
referring to recurrent abdominal pain and should be used only in reference to the
duration of the syndrome because each pain episode is distinct and separated by
periods of wellness. [7] Although RAPS does occur in the preschool-aged
population, it is rare in children less than 5 years or older than 15 years. [50] It is
most frequently encountered in school-aged children (10-12 y of age), [130] with
an incidence of 10% to 19.2% in this age group. [2] [94] Girls are affected somewhat
more than boys at a ratio of 5:3. [50]
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Only 10% of children with RAPS are eventually found to have a recognizable
organic cause for their complaints. [14] Apley [3] and Apley and Naish [4] originally
suggested that nonorganic RAPS occurred among timid and tense children.
Similarly, using age-matched controls, Lundby and colleagues [74] showed that
RAPS occurred more commonly in anxious children who had suffered a greater
number of stressful experiences before the onset of their symptoms. [74] Lower
socioeconomic status, family psychopathology, and life events have all been
associated with RAPS. [51] [52] [53] The potentially dangerous conclusion from these
studies is that children who complain of recurrent abdominal pain are unlikely to
have organic cause. Although statistically speaking this may be true, nonorganic
RAPS should be a diagnosis of exclusion.
Clearly, the most effective approach to the evaluation of children with RAPS
requires an understanding between the interplay of somatic and psychogenic
factors. To this end, Levine and Rappaport, building on earlier models, [8] [94] have
suggested a comprehensive model that conceptualizes RAPS to be a result of
multiple interacting forces. These forces include somatic dysfunction or disorder,
lifestyle and habit, critical life events, and temperament and learned response
patterns. [72] These forces converge to determine the type, extent, and impact of
these children's pain.
Organic Causes of Recurrent Abdominal Pain
A review of possible causes of recurrent abdominal pain

in children encompasses a comprehensive review of pediatric medicine. Levine
and Rappaport [72] have listed several physiologic derangements that may
predispose children to recurrent abdominal pain in (Table 3) (Table Not
Available) .
Children with RAPS typically present with complaints of periumbilical, visceral
pain of less than 1 to 3 hours' duration, which are often associated with functional
or autonomic symptoms of nausea, vomiting, pallor, perspiration, flushing,
palpitations, or headache. Thus, on initial presentation, RAPS may mimic any of
the aforementioned acute abdominal conditions and thus may prompt extensive
evaluation, leading to unnecessary invasive investigation or surgery.
Diagnostic Workup
In the acute setting, patients with signs, symptoms, or physical findings to

suggest an acute condition should have the diagnosis pursued by appropriate
testing regardless of a history of RAPS. As with any acute abdominal condition,
surgical consultation is needed.
When referred for elective evaluation, investigation should proceed with an

understanding of the many factors, both organic and psychogenic, that may be
contributing to these children's complaints. Red flags (Table 4) (Table Not
Available) that may herald organic disease should alert physicians and prompt a
more aggressive approach to diagnosis. [72] Clinicians' primary focus should be to
exclude organic disease, and it is important to avoid a "shotgun-blast" approach
to diagnosis. A careful history and physical examination should logically lead to
the most appropriate
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TABLE 3 -- POTENTIAL ORGANIC CAUSES OF RECURRENT ABDOMINAL

PAIN
From Levine MD, Rappaport LA: Recurrent abdominal pain in school children: The
loneliness of the long-distance physician. Pediatr Clin North Am 31:969-991, 1984; with
permission.
(Not Available)
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TABLE 4 -- RED FLAGS FOR ORGANIC CAUSES OF RAPS
From Rappaport LA, Leichtner AM: Recurrent abdominal pain. In Schechter NL, Berde
CB, Yaster M (eds): Pain in Infants, Children, and Adolescents. Baltimore, Williams &
Wilkins, 1993, pp 561-569; with permission.
(Not Available)
and productive testing modalities. Usually, children are referred for evaluation
of RAPS following one or more previous consultations, in which a battery of
testing may have already been completed. Careful review of previous testing is
required to avoid the cost and trauma of repeated studies.
Because most studies show that one third of organic causes of RAPS are
gastrointestinal or genitourinary, it is reasonable to focus on these entities. A
complete blood count, sedimentation rate, and liver and renal function tests can
be quite useful initially to rule out anemia, inflammation, and hepatic or renal
dysfunction. A urinalysis should be obtained from all patients, and a urine culture
should be performed in girls. Guaiac testing of the stool is also indicated. Lactose
breath testing in children with a history suggestive of lactose intolerance is
indicated. Patient populations at risk for giardia and parasitic infection should
have stool testing for ova and parasites.
Extensive radiographic evaluation of children with RAPS is rarely diagnostic or

cost-effective. [115] Sonography, in particular, advocated for its noninvasiveness
and because it involves no radiation exposure, yields positive findings
in children with RAPS in only 3% to 7%. [109] [115] [122] Diagnostic imaging should
be pursued logically according to the child's history and pertinent physical
findings. [72]
Management
As stated earlier, 10% of patients with RAPS have definable organic cause. On
the other hand, longitudinal studies of children with RAPS show that only one
third have resolution of their pain within 5 years, whereas an additional 25% to
50% exhibit similar symptoms into adulthood. [21] [50] [75] Upon exclusion of organic
causes of RAPS (see Table 3) (Table Not Available) , the next step may involve
reassurance, referral, continued observation, or more invasive investigation.
What to Do with the Unknown

Rappaport and Leichtner [94] have outlined the following guidelines that may be
used to establish a system for optimum continued management of families and
patients without definable cause of their pain.
1. Explain and Reassure. Carefully explain to the family and the child the
concepts and reasoning behind all investigations. Ask the parents about
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any particular concerns or disease they believe to be the culprit of the

child's pain. Once organic cause has been systematically ruled out,
reassure the patient and family that no major illness is present.
2. Identify red flags. Make sure that the parents fully understand objective
signs indicating severe illness. Have them keep you informed of such
changes and provide guidelines for what to do if they occur.
3. Avoid psychological "labeling." Unless evidence supports the contrary, do
not suggest that the child's pain is psychological or that the child may be
malingering.
4. Allow normal activity. Encourage normal activity between times of pain.
5. Watch for withdrawal. If the child begins to withdraw from normal
activity, psychological referral should be considered over escalating pain
management.
6. Establish regular follow-up. Establish a system of regular return visits to
monitor the symptoms.
7. Be available. Assure parents that you are available to see the child if
changes occur or the parents become anxious. Allow appropriate time, in
an unrushed environment, for them to be seen.
8. Beware the placebo response. Avoid making an immediate diagnosis
based on a therapeutic response. Placebo effects, particularly involving the
gastrointestinal tract, can be misleading.
9. Make judicious use of "second opinions." Be open to requests for second
opinions, particularly for anxious patients and families. Assure the parents
that you will continue to help manage their child's problem even after a
second opinion is obtained.
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Pediatric Clinics of North America

Volume 45 • Number 6 • December 1998

PEDIATRIC SURGERY FOR THE PRIMARY CARE

THE APPROACH TO COMMON ABDOMINAL DIAGNOSES IN

Address reprint requests to

An original report by Hirschsprung, presented at the Pediatric Congress in Berlin

colleagues, and Swenson and colleagues, in separate reports, described the

Epidemiology and Anatomy

Congenital megacolon is caused by failure of migration of enteric ganglia

The understanding of the effect of proper versus diseased innervation of the GI

Clinical Findings at Presentation

With an increasing number of cases diagnosed in the newborn period, failure to

The required diagnostic test to diagnose Hirschsprung's disease is a rectal biopsy

In virtually all cases of suspected Hirschsprung's disease, a plain abdominal

Special Diagnostic Concerns

Total colon Hirschsprung's disease and ultrashort-segment Hirschsprung's disease

With ultrashort-segment Hirschsprung's disease, children usually have been seen

Hirschsprung's disease in the newborn period can present similarly to other

Infants presenting with obstructive symptoms:

Atresia (anal, colonic, jejunoileal)

Meconium plug syndrome or ileus (cystic fibrosis)

Gastrointestinal tract duplication

Incarcerated hernia (inguinal or internal)

Small left colon syndrome

Seriously ill infants with obstruction:

Malrotation with volvulus

Maternal cocaine or heroin use

Sepsis with ileus

In more seriously ill infants, conditions to be considered in the differential

In older children, Hirschsprung's disease is frequently confused with functional

In all cases of Hirschsprung's disease, operative intervention is the definitive

One-stage repair is feasible in all patients, including newborns less than 4

The complications pertaining to colostomy creation and removal are

Outcome studies reveal similar complication rates and functional results

Therefore, the authors' current recommendations on treatment for Hirschsprung's

The issue of open versus laparoscopic one-stage procedures is not as clear.

Long-Term Complications, Prognosis, and Follow-Up

As previously described, evaluation of long-term results for all three operations is

In incontinent patients, manometric evaluation may reveal poor sphincter

Approximately 25% of children in most large series receive reoperation for

*References [16] [46] [70] [83] [87] [121] [123] [127]

stenosis, prolapse, bowel obstruction, abscess drainage, sphincterotomy, or

Hirschsprung's enterocolitis can occur preoperatively and postoperatively (either

In the preoperative period, the cause of Hirschsprung's enterocolitis is thought to

A recent report evaluating postoperative factors causing Hirschsprung's

SURGICAL DISORDERS ASSOCIATED WITH BLEEDING

Gastrointestinal bleeding is a rare occurrence in pediatric patients. In this patient

It is important to be precise when describing the patient with gastrointestinal

TABLE 1 -- COMMON CAUSES OF UPPER GASTROINTESTINAL HEMORRHAGE

Physical examination in the patient suspected of having GI bleeding includes

A nasogastric tube to help prevent aspiration and to ascertain whether the

The magnitude of bleeding is reflected in the physiologic status of

Two, large-bore peripheral intravenous catheters should be placed, and

The diagnostic approach to upper GI bleeding (Figs. 1 and 2) and lower GI

Upper Gastrointestinal Bleeding

Upper GI bleeding results in "coffee ground" emesis, hematemesis, melena, or

Figure 2. Diagnostic approach to upper gastrointestinal hemorrhage in children and

Figure 3. Diagnostic approach to lower gastrointestinal hemorrhage in infants

hydroxide; fetal hemoglobin, resistant to reduction, remains a pink or bright red

Esophagitis in infants and children usually occurs as a result of gastroesphageal

Most newborns and infants with gastritis, gastroduodenal ulceration, or both,

Figure 4. Diagnostic approach to lower gastrointestinal hemorrhage in children and