SA MEDICAL JOURNAL VOLUME 62 4 DECEMBER 1982 887

Cholelithiasis in childhood and

adolescence
A review
R. POLLAK, H. M. REYES, K. C. PRINGLE
Summary
Cholelithiasis and cholecystitis are uncommon in
childhood and adolescence. Misconceptions as to
the aetiology, natural history, diagnosis, and the-
rapy of these conditions prompted us to review our
experience. Nineteen patients ranging in age from 7
to 18 years underwent cholecystectomy for gall-
stones at the University of Illinois Hospital, Chi-
cago, between June 1970and June 1979. Seventeen
patients were female and 2 male (ratio 8,5:1). The
cause was unknown in 12 patients (63%) but in 7
patients (37%) haematological disease was the
underlying disorder.
The most common presenting symptom (95%)
was vague right upper quadrant or epigastric pain,
often ignored or mistaken for peptic ulcer pain.
Oral cholecystography demonstrated gallstones
in 15 of 16 patients. Ultrasonography, used more
recently, was positive in 3 patients. Intra-operative
cholangiography in 12 patients, and common duct
exploration in 1 additional patient, failed to demon-
strate calculi. No patients were readmitted for recur-
rent or retained biliary calculi after cholecystectomy.
S AIrMed J 1982; 62: 887-889.
Cholelithiasis and gallbladder diseases are uncommon in child-
ren and adolescents. The first well-documented case of hydrops
of the ga.llbladder in a child was published bi: GibsonI in 1734.
Interest ID the subject was renewed by Potter .3 in 1927and 1938
and since then a number of excellent reviews have covered the
topic in depth.
4
-
8
Despite these studies, controversy remains as
to the causes and natural history of gallstones in individuals
under 18 years of age, as well as important aspects of diagnosis
and correct management.
This review attempts to provide a rational diagnostic and
therapeutic approach to the child with gallstones.
Patients and methods
A retrospective study was undertaken of all patients under 18
years of age at the University of Illinois Hospital, Chicago, who
Division of Pediatric Surgery, Abraham Lincoln School of
Medicine, University of lliinois, Chicago, lliinois, USA
R. POLLAK, M.B. B.CH., F.R.CS.
H. M. REYES, M.D.
K. C. PRINGLE, M.D., M.B. B.CH., F.R.ACS.
Date recei\"ed: 16 Februan" 1982.
Reprint 10: Dr Raymond Pollak, Dept of Surgen", l"ni\"ersit\" of at the i\'\edical
Cemer, PO Box 6998, Chicago, Ill. 60080, CSA. . .
had undergone cholecystectomy for cholelithiasis during a 10-
year period, June 1970 to June 1979.
Patients were evaluated in terms of age, race, sex, underlying
predisposing factors (induding parity) and presenting clinical
syndrome. The diagnostic work-up consisted of plain radio-
graphs of the abdomen, oral cholecystography, haematological
studies and, lately, abdominal ultrasound examination. The
operative findings, results of operative cholangiography, and the
presence or absence of common bile duct stones were similarly
noted.
Results
Nineteen patients ranging in age from 7 to 18 years were ope-
rated on for cholelithiasis during the period under review. Thir-
teen patients were Black, 4 Hispanic, and 2 White. Seventeen
patients were female, 2 male (8,5: 1). Four patients had sickle cell
anaemia and I patient each had sickle spherocytosis, sickle tha-
lassaemia and sickle cell trait; a total of7 patients with underlying
haematological problems (36,8%). Two patients had previously
had abdominal surgery (10,6%). The 2 males both had sickle cell
disease associated with their'gallstones.
Eighteen patients presented with a syndrome of vague right
upper quadrant or epigastric pain (95%) and only 2 patients
presented with clinical jaundice.
Recent weight loss and obesity were not prominent features in
the group under study. Nine of the females were parous or on
oral contraceptives. In only 2 patients (10,5%) were radio-
opaque calculi seen on plain abdominal radiographs. Sixteen of
the 19 patients had oral cholecystograms, IS of which outlined
stones in the gallbladder. Three patients had ultrasound study of
the gallbladder; all proved to have gallstones at operation. The-
rapy in all cases consisted of uncomplicated surgical ablation of
the gallbladder. Twelve patients had intra-operative cholangio-
graphyand I patient underwent common bile duct exploration;
no stones were found in the common duct in any of these 13
patients. No patient has returned with retained or recurrent
common duct stones, although it should be borne in mind that
the period of follow-up is short. Overall I% of patients who
underwent cholecystectomy were children.
Discussion
The assessment of the child or adolescent with abdominal pain
presents a challenge of some magnitude to the clinician. Choleli-
thiasis and cholecystitis are uncommon in children and are often
excluded in the differential diagnosis of abdominal pain in these
patients. Autopsy studies have revealed that the incidence of
cholelithiasis in children is less than 0, I%.4 The clinical incidence
varies from 0,13% to 1,5% in quoted series of all patients with
biliary tract disease, and this would confirm our findings.
s
Cholelithiasis occurs more commonly than acute cholecystitis
6
.
8
and no patient in this series presented with the classic features of
acute cholecystitis. The age range is variable, and calculi have
been observed in stillborn fetuses.
4
.
9
Females predominated in
888 SA MEDIESE TYDSKRIF DEEL 62 4 DESEMBER 1982
our series as they do in most other published reviews, although
one study claims a male preponderance.
6
The racial incidence is
of importance when viewed in relation to the occurrence of
haemolytic disorders. The racial variation also directly reflects
the hospital population and the community it serves; it explains
the greater number of Black children with cholelithiasis in our
series. Similarly geographical, genetic, and dietary factors may
also need to be assessed, as evidenced by the high incidence of
biliary tract disease in Pima Indians in the USA.lO
The causes of gallstones in children have been grouped by
Brenner and Stewart" into six categories: (i) infection and infes-
tations; (ii) anatomical - congenital and acquired, or external
compression; (iii) constitutional, including obesity, recent weight
loss, and hypertension; (iv) metabolic (hypercholesterolaemia)
and hormonal; (v) hereditary - 20% of patients have a familial
history in some series;4.6 in others, as in ours, this was absent; I I
(vi) haemolytic.
Many of the literature reviews cited have various postulates on
aetiology, some of which fall into the categories mentioned
above. Blanket statements that 'gaIlstones are commonly due to
haemolytic disease in older children' 10 are only correct in one-
third to one-half of the cases and again depend on the age group
studied and the hospital population being served.
In our experience, in most cases there is no satisfactory expla-
nation for the occurrence of gallstones. The high incidence of
parity in our series confirms other published figures
l2
of the
association of cholelithiasis with pregnancy. The derangements
of cholesterol and bile salt metabolism produced by the hormo-
nal upheaval of pregnancy have been well demonstrated,13 and
may be a factor operating in some ofour patients. Why all parous
females do not get gallstones is still not adequately explained.
The third important group to consider are those patients who
have an underlying haemolytic disease, 36% in our series. The
number of children with biliary tract disease who have haemo-
lytic anaemia varies from less than 10% to 45%,4,11,12 depending
on the referral patterns at the hospital concerned. Conversely,
the incidence of cholelithiasis in children with haemolytic di-
seases varies from 6% to 70%.4.14.15 This wide variation is largely a
function of age; the incidence tends to be lower in younger
patients and we might expect that almost all these children will
develop gallstones during their lifespan if followed up for long
enough periods. '4 In this series, the children with haemolytic
disorders were all referred for elective cholecystectomy after
presenting with vague abdominal and/or right upper quadrant
pain.
The clinical presentation varies from florid acute cholecystitis
to almost no symptoms at all. A history of fatty food intolerance
was not recorded in any of the patients in this series, although
14 - 35% of patients in other studies volunteered this informa-
tion.
4
,11,16 Younger children wiIl rarely complain of or confirm
fatty food intolerance.
s
Sixty per cent complain of pain in the
epigastrium and right upper quadrant,4 a fmding which our
review confirms, The specific symptoms of nausea and vomiting
together with pain can present a confusing array of differential
diagnoses and resulted in delayed recognition of up to 10 years in
one series.
ll
The presence of jaundice should be carefully looked
for. Most cases are haemolytic or inflammatory in origin, but
may still be due to a common duct stone. Only 1 patient in this
series had jaundice due to hepatitis, but in other series an inci-
dence of 24-25% has been reported.
4
A mass in the right upper
quadrant is rare and found only in 10,7% of cases,4
The pre-operative rate of misdiagnosis is said to be as high as
18-20%, hence the need for accurate pre-operative work-up.
The plain film of the abdomen will demonstrate only 10% of
calculi and, as confirmed in our study, had limited value. One
study, however, claims that it is of diagnostic importance.
l
'
Oral cholecystography is confirmatory in 75-80% of cases,
with a 95% positivity rate in our series. The technique for child-
ren is similar to that for adults, except for infants in the first few
months of life.
4
Abdominal ultrasonography is a non-invasive
technique for evaluating the biliary tree, and will accurately
indicate the presence of gallstones in 90% of patients.
18
,19 It will
demonstrate the presence or absence of dilated extra- and
intrahepatic ducts. In 2 of the 3 patients in this study who
underwent ultrasonography it was the only pre-operative inves-
tigation and was completely successful. It is an easy, cheap
outpatient study and has an important role in the diagnosis of
abdominal pain in children and in those in whom the results of
oral cholecystography are questionable. For children in our insti-
tution it has become the initial diagnostic procedure in the
work-up of cholelithiasis. Recendy, radionuclide imaging of,the
biliary tract has come into use with the development of 99mTc_
labelled biliary tracers.
20
Other routine laboratory assays a r ~ of
importance, notably that of the alkaline phosphatase levet to
assess hepatic excretory function.
Surgery is the only form of therapy for choleli thiasis if morbi-
dity and/or mortality is to be avoided.1.
21
In our series there were
no deaths or complications; this compares with a quoted opera-
tive mortality rate of 0,9%.4 Common duct stones are rare in
children, occurring in only 6-10% of reported cases,4,8 and the
role of intra-operative cholangiography is therefore controver-
sial,17 In our series, 13 patients had intra-operative cholangio-
graphy and 1 patient underwent common duct exploration because
of the presence of jaundice. All procedures failed to show the
presence of common duct stones, despite the presence of small
stones in the gallbladder. We no longer perform operative cho-
langiography routinely, or common duct exploration, unless
dilated ducts are seen pre-operatively on ultrasonography or are
found in the operating room, or there is a history of pancreatitis
or jaundice in the absence of haematological disease.
In children with haemolytic anaemia concomitant splenec-
tomy has been frowned upon," but with modem techniques the
procedure is safe;s where necessary we remove the spleen.
Conclusions
On the basis of our findings and a reviewof the literature to date
we may make the following points:
1. Cholelithiasis and cholecystitis are uncommon in childhood.
2. Clinical signs and symptoms are nonspecific, the main
symptom being epigastric pain.
3, The cause is unknown in the majority of patients, and
related to haematological disease only one-third of cases.
4. In the absence of jaundice, oral cholecystography is reliable
for demonstrating stones in the gallbladder.
5, Ultrasound is an important diagnostic tool for demonstra-
ting stones in the gallbladder as well as the presence of dilated
intra- or extrahepatic bile ducts.
6. Operative cholangiography should not be routine in child-
ren and should be reserved only for patients in whom dilation of
the intra- or extrahepatic bile ducts is demonstrable either by
ultrasonography (pre-operatively) or at the time of cholecys-
tectomy.
REFERENCES
1. Gibson]. Medical Essays and Obsen.'Q/ions, \'01. 2. Edinburgh: Philosophical
Society of Edinburgh, 1734: 352.
2. Poner AH. Gallbladder disease in young subjects. Surg Gynecol Obste1 1927;
46: 795-808.
3. Poner AH. Biliary disease in young subjects. Surg Gynecol Obscel 1938; 66:
604-610.
4. Brenner RW, Stewan CF. Cholecystitis in children. Re<' Surg 1964; 21:
327-335.
5. Grai\'ier L, Dorman GW, Voneler TP. Gallbladder disease in infants and
children. Surgery 1963; 63: 690-696.
6. Seiler I. Gallbladder disease in children. Am] Dis Child 1960; 99: 662-666.
7. Vlin AW,Nosal]l, Manin WL. Cholecystitis inchildhood.]AMA 1951; 147:
1443-1444.
8. Vlin AW, Nosal ]1, Manin WL. Cholecystitis in childhood; associated
obstructive jaundice. Surgery 1952; 31: 312-326.
SA MEDICAL JOURNAL VOLUME 62 4 DECEMBER '982 889
9. Walker CHM. Etiology of cholelithiasis. Arch Dis Child 1957; 32: 29:>-297.
10. Bennion LJ, Knocoler WC, Mon DM ec al. Development of lithogenic bile
during puberty in Pima Indians. N Engl] Med 1979; 300: 87:>-876.
11. Soderlund S, Zenerstrom B. Cholecystitis and cholelithiasis in childhood. Arch
Dis Child 1962; 37: 147-179.
12. MH, Jannena PJ. Cholecystitis in ado!escents.rJm] Dig
Des 19/4,1/.68-/_.
13. Glenn F, 1\kSherry CK. Pregnancy, cholesterol metabolism and gallstones.
Ann Snrg 1969; 169: 712-723.
14. Arijan S, She;;el Fj, Picken LK. Cholecystitis and cholelithiasis masking as
abdominal crises in sickle cell disease. Pediacrics 1976; 58: 252-258.
15. Cameron J L, Maddrev \X"C, Zuidema GO. Biliarv tract disease in ,ickle cell
anemia. rIml Surg 197i; 174: 702-710. -
16. Kin!e, JA, Holcomb GW. Surgical management ofdiseases of the gallbladder
and common duce in children and adolescents. Am] Snrg 1966; 111: 39-46.
17. Moosa AR. Cholelithiasis in childhood.] R Coil Snrg Edinb 1973; 18: 42-46.
18. DouS! BD, Maklad I'F. Cltrasonic B-mode examination of the aallbladder.
R<1dioiogy 1974; 110: 643-647. "
19. Kappelman NB, Sanders RD. l'lrrasound in the imeS!igation of gallbladder
disease. ]A."'tA 1978; 239: 1426-1428.
20. Sty JR, Glicklich M, Babbin DP, Starshak RJ. Technetium-99m biliary
lmagmg In pedlarflc surgical problems.] Peo'iu{r Surg 1981; 16: 686-690.
21. Lund J. Surgical indications in cholelithiasis. Ann Snrg 1960; 151: 153-162.
and glycosylated
in the assessment of
non-insulin-dependent
young
Fasting plasma glucose
haemoglobin levels
diabetic control in
diabetes in the
I. JIALAL, S. M. JOUBERT, D. KENDALL
Summary
Response to diet and drug therapy was assessed in
a group of 85 Indian patients with non-insulin-
dependent diabetes in the young (NIDDY). There
was a significant decrease in fasting plasma glucose
(FPG) values on therapy (pretreatment 13,3 0,5
mmol/I; post-treatment 9,7 0,4 mmol/I) (P<0,001).
Prior to therapy the majority of patients had either
moderate (40%) or severe (59%) diabetes; on therapy,
the majority had either mild (21%) or moderate
(62%) diabetes. Estimation of glycosylated haemo-
globin (Hb A,) levels revealed that control was
excellent (Hb A, <10%) in 47%of patients and excel-
lent-or adequate (Hb A, in 78%. Hb A, levels
correlated significantly with the FPG value (r=0,78;
P < 0,(01). In 8 patients with iron deficiency anae-
mia the Hb A, level did not fall within the correlation
norms between Hb A, and FPG. Treatment of the
anaemia restored the correlative norms. Hb A,
levels were significantly higher in patients with
microvascular complications (12,1 0,8%) than in
those without any vascular complications (10,3
0,3%) (P < 0,01).
S Afr Med J '982; 62: 889-891.
Department of Chemical Pathology, University of Natal,
Durban
1. JIALAL, M.B. CH.B.
S. M. JOUBERT, M.Se. M.B. CH.B., F.R.e. PATH.
D. KENDALL, DIP CHEM PATH.
Reports on non-insulin-dependent diabetes in the young
(NIDDY) in its most classic form with autosomal dominant
inheritance (MODY) would suggest that it is a mild non-
progressive disorder bordering on chemical diabetes and that
good control is usualll achieved by diet and the use of oral
hypoglycaemic agents. -4
Campbe1l
5
also obtained good control with oral hypoglycae-
mic agents (mainly chlorpropamide) and dietary restriction in
Natal Indians with NIDDY. However, Cosnett
6
found that oral
therapy resulted in improvement in less than 20%of his group of
Indians with NIDDY. It was therefore of interest to study the
control achieved by diet and oral hypoglycaemic agents in the
group of Indians with NIDDY which we have been
studymg, usmg more ngorous cntena m assessmg the control
achieved.
Patients and methods
The 85 Indians with NIDDY studied have been reported on
previously and full clinical details have been given.' All were
advised to adhere to a low-carbohydrate diet by a dietitian and
issued with a diet sheet.
Since euglycaemia could be achieved in only I patient by diet
alone (she had a normal fasting plasma glucose level), therapy
with the oral hypoglycaemic agents was instituted in the remain-
ing 84 patients. The drugs used and the maximum doses offered
are given in Table 1. Chlorpropamide or glibenclamide, usually
in combination with phenformin, was most commonly used. All
patients were followed up for a minimum period of I year on
therapy. The patients were seen monthly, and in addition to a
clinical assessment and examination of the urine for glucose,
ketones and albumin, blood samples were withdrawn for plasma
glucose and glycosylated haemoglobin (Hb AI) estimation. Hb
AI levels were determined on the same day that the samples were
taken, by cation exchange chromatography at 22C. Controls