Tohoku
J. exp.
Med.,
1975,
115, 99-110
Reconstruction of Intrahepatic Congenital Biliary Atresia
Bile Ducts
TSUNEO CHIBA, MORIO KASAI and
in
NOBUAKI SASANO*
The Second Department of Surgery and The Second Department of Pathology*, Tohoku University School of Medicine, Sendai
CHIBA, Ducts
in
T.,
KASAI,
Congenital
-Macroserial 7
cases
biliary
according
studies,
it
through
the
performed
was
one
duct
and
to
tion
of
be
has
also In
in of
with
cause seen view
biliary
intrahepatic
of
and
a number
of
atresia.
As
of
these
infants facts
the
severe or
with
this
operation
ducts;
usually
small
ducts. tract
These
one
of an
case
many of
the
cholangitis of
intrahepatic
without early
results in
ascending
disease
around
obtained
in
of
patent
portal
duct. was
in
cases
a network
biliary
ascending
made 4
bile
disappearance
atresia. -congenital bile
main bile
observed
of
destruction
older
of
a
99-110
reconstruction
are
make
the
was
extrahepatic of
Bile
(2),
and
ducts
the
ductules
excretion
ducts
of these
ductules
with
active
of
in
results
of
115
type ‡U
bile
atresia
ducts
biliary
the
Intrahepatic
1975, bile
of
interlobular
type
of
Med.,
1 case
From
main
that
exp.
intralobular I,
complication
important
cholangitis.
recommended struction
an
Reconstruction J.
communications
fact
postoperative
which
type
that
some the
main
of
bile
disclosed
have
the
the
of
with
series,
ducts,
the of
patients
present
cases
that
case
N.
Tohoku
classification.
reconstruction
postoperative
bile
Kasai's
regardless
compatible
seemed
2
confirmed liver
in
main
were
SASANO,
of
atresia; to
microserial
the
and Atresia.
reconstruction of
type ‡V
A
M.
Biliary
stage atresia;
complica of
life
is
recon
cholangitis
The pathogenesis of biliary atresia is not known. Although many kinds of study have been performed up to the present, the true cause of the disease is not clear. Recently, it has been reported by several authors that this disease may result from some inflammatory process of the liver and biliary tract during intrauterine life. Knowledges about the pattern of the bile ducts seem to be a prerequiste for studying the cause of this disease. The form of the intrahepatic biliary tree can be demonstrated by x-ray films with contrast medium, a cast using resin, and histological reconstruction. The normal structure of intrahepatic biliary tree was previously described by Healey (1953). In the liver of biliary atresia, however, visualization of the bile ducts with contrast medium or resincast is practically impossible. Therefore, the technique of histological reconstruc tion is required for demonstration of bile ducts in the liver. There have been some reports on this subject, but most of them are concerned with the structure of bile ducts and ductules in the peripheral liver specimen. The present report describes the study of intrahepatic main bile ducts extending from the porta hepatis to the periphery of the liver in biliary atresia. Received
for publication,
November
19, 1974 99
100
T. Chiba
et al.
MATERIALS AND METHODS Autopsy the
was
past
were
four
obtained
specimen
was
cularly to of
an
the
porta
to
2500 ƒÊm. the
for
were
agent.
In
(Fig.
was
fixed
1).
in
6
cases,
case ether
xylene
(Case
and
imbedding
2),
in
liver
numbers
were
paraffin
was
used
written
solvent for
paraffin
blocks
were
to
serial
was the
each
block
alcohol,
with
the
these
dehydrating
imbedding).
solvent
after the
blocks
2000
thickness
tissue
with
(paraffin
cutting perpendi
about
on of
In
the
the
infiltration
process
without
a
perpen
and
block
After
wooden
liver
cases
surface
paraffin
imbedding).
attached
tissue
miscible
solvent for
6
dehydration is
study
abdomen,
fixation, in
the
during
the
depending
on
which
used
(celloidin-paraffin
tissue
each
hours present
the of
After
Following
was
periphery
variable,
the
from
hepatis
of
was
direction.
the
porta
thickness block
the
the
of
removed
formalin.
to The
3 postmortal
materials
was to
neutral
tissue
and
within The
hepatis
10%
chloroform
celloidin
these
the porta
1 case.
site to
the
the
atresia
Hospital.
After
and
the
biliary
horizontally
of
Marks
of
cases.
slicer
transferred
remaining with
from
number
confirmation
blocks
bloc
hepatis
The
liver
en
electric
of
University
7
specimen
with
7 cases
Tohoku
these
excised
The
made
in
at
from
dicularly. was
performed
years
of
paraffin
distortion
of
the
direction.
Fig. 1. Serial of
sections
Case
2.
Each
section
other
was
with
elastica-Masson
such
as
eosin.
After
the
macroserial was
similar
in
cases,
about
also
6 ƒÊm
and
the
staining,
All
a
6 ƒÊm
stain
vessels
tion.
tract
of
In
the
A part of serial tissue blocks of the liver (Case 7).
made technique.
and
graphic in
in for
like. all
ducts
addition
thickness
were
10 thickness.
good
sections
A
obtained
large
were
the
projected
within
macroserial
of
the of
large
the
bile
reconstruction
every
the
were paper
and of
large
ductules bile
in ducts
tissues
hematoxylin
high
were
stained
other
with
under
block.
were
from
stained
demonstrated
ducts
blocks
paraffin
sections
cholangioles
tracing
tract
celloidin-paraffin
from of
sections on
portal
every
majority of
number
reconstruction to
from
were
discrimination
A small
ductules
prepared
sections
magnifica
traced a in
small Case
.
Thus portal 2 with
Intrahepatic
Bile Ducts
in Biliary
Atresia
101
RESULTS AND DISCUSSION According bile
duct
III,
in
to
were
6 and
were
cases
are
to
Case
1.
Y.M.,
total
the
of
duodenum
was
obstruction made
was
was
not
after
operation.
was
completely
and
Histologically proliferation
canaliculi
and in
bile
lobules.
comparatively (Fig.
many
large 4)
bile
2),
the
duct
found
cut
surface
that
Photomicrograph
found. the
main
pregnancy
for
not
Hospital
weighed
400
g,
periportal
zone
were
in
ductules adjacent
The
bile
was
only
18
days duct
firm
and
were
tracts
and
the
porta
hepatis,
duct
liver specimen
in
intrahepatic
was
open
in Case 1.
in
moderate cells
portal
of
the
bile was
Hepatic
reconstruction
interlobular
of the peripheral
to
of
died
fibrosis
in
type
common which
seen.
the with
postoperative
She the
the
on
duct
The
of
on
and
performed
bile
decrease.
g. was
communication
patient.
the
2,850 She
The
portion
in
was
bilirubin
was no
common
the
distal
marked
were
was
other
interesting
University
and
with
did the
periportal
plugs
On
demonstrated
Fig. 2.
the
as type
the
jaundice.
operation
of
liver
(Fig. in
2,
and
birth
cholangiography.
bilirubin
The
Case
two
of at
test
dilated
fistula
that
toxemia
Tohoku
The
condition
serum
extrahepatic
male and
weight
Schmidt's
was
external
revealed
obliterated.
degenerated
ducts
good
duct
general
in
6 was
neonatal
Surgery,
intraoperative
An
poor
Autopsy
consistency. ductular
Ia.
the
type ‡Ub
from
after
ml.
bile
of the
types
Body
negative
mg/100
as Case
various
normal.
of
by
7.
suffered
was
14.6
4,
and
findings
:
mother
showed
disclosed
of
5
following
common
Kasai's
because
course
The
gross
1 and
3,
manifested
stool
was
life.
Cases
Department
The
bilirubin
day
the
delivery
Second
1966),
representing
continuously
1971.
serum
228th
in Cases
Her
the
been
to
in
female. but
18,
Ia in
cases
described
had
admitted
the
be
(Kasai
type
type ‡Vb Three
pregnancy,
January
as
as
female.
Jaundice
classification
classified
Case
cases
late
Kasai's
bile a bile
along
its
102
T. Chiba
Fig. 3.
Photomicrograph
Fig. 4. A graphic reconstruction of some branches of intrahepatic bile duct in Case 1.
et al.
of the liver
in Case 2.
Fig. 5. A graphic reconstruction of some branches of intrahepatic bile duct in Case 2.
whole length through the liver. The reconstructed bile duct seemed to be the medial superior duct of the left lobe. The reconstructive findings of a bile duct in Case 4 which died 6 months of life were similar to those in Case 1. Case 2. M.J., female. Her mother was in good health during the pregnancy. Body weight at birth was 3,000g. Persistent jaundice appeared after the neonatal jaundice once disappeared. She was admitted to our clinic on January 11, 1971.
Intrahepatic
Fig.
Total
serum
89th
day
life.
be
After
jaundice
the
However,
liver
and
weighed
350
disclosed
feration
was
with
that
ducts
and
the
periphery Case
3.
birth to
19,
the
on
duct classified
bile
g.
al.
The
open
study
the
main
the
the
proli
microscopic is
consistent duct
duct, of
their
of
draining
main
along
existed.
Ductular
finding
reconstruction
hemor
kidneys
shows This
(1969).
were
both
3).
6
block.
surrounded
ducts
subsequent that
Histological
Fig.
one
macroserial
of
life
duct
Kasai's ‡Vb.
suffered
was
occasionally
intrahepatic
whole
were
fibrous, Fig.
7
10
bile
length
to
the
while shows
the a
left
ml.
The
hepatic
hepatic
bile
ducts.
common
was of
on
operation
duct,
duct slide
was
Hospital
extrahepatic
right
histological
Body She
University
of
The
pregnancy.
disappear.
mg/100
obliteration
lumen.
of
not
Tohoku was
a total a small
toxemia did
Surgery,
bilirubin
revealed with
from
jaundice of
serum
atrophic
cystic
mother Neonatal
Department total
day
was
as
The
Her
Second
88th
and
et
ductules shows
2,700
The
gallbladder
Oh-i
5
female. was
1971.
performed
in
al. and
liver.
K.K.,
at
July
liver.
the
by of
Fig.
zones.
ductules
and
(Fig.
et
fistula
revealed of
firm. fibrosis
periportal
and
number it.
same
of
admitted
a
relatively
periportal
(Sawaguchi
Autopsy swelling
the
contrast type ‡Ub).
external
hematemesis
and
the
(Kasai's
performed
the
atretic,
and
duct
on
were
dilated
this
of
performed
duct
bile
day.
was
the
duct described
with
of
weight
in
bile
previously
connecting
which
was
were
was
lungs
in Case 2.
cystic
through
died
both
irregular
noticed of
preserved
g,
marked
reconstruction
she
of
and
fistula
postoperative
edema
tract
intrahepatic
excreted
103
operation
duct
radicles
external
38th
The
bile
the
bile
the
ml.
into
Atresia
of the portal
hepatic
with
on
pneumonia
liver
and
both
operation,
edema
rhagic
hepatic
common
injected
diminished.
pulmonary
The
mg/100
the and
easily
in Biliary
reconstruction
14.6
porto-jejunostomy
1968).
The
duct
could
Hepatic
was Although
hepatic
medium
A graphic
bilirubin of
common
6.
Bile Ducts
not
macroserial
seen
inn
T. Chiba
et al.
Fig. 7. Macroserial sections of the extrahepatic bile ducts in Case 3. duct; G, gallbladder; H, hepatic duct (right); L, liver specimen.
Fig. 8.
Photomicrograph
of the
liver
C, common bile
in Case 3.
sections of the extrahepatic bile duct removed from this patient. Hepatic porto jejunostomy with Witzel-type fistula was performed. The tube jejunostomy was excised and double-barreledjejunostomy was made 10 days after the first opera tion because intestinal decompressionthrough the tube was inadequate (Suruga 1970). After the second operation the general condition of the patient became worse and died of the anastomotic leakage 67 days after the first operation. The liver weighed 500 g, which was firm in consistency at autopsy. As shown in Fig. 8, the liver histologically showed moderate ductular proliferation. An
Intrahepatic
Fig. 9.
Fig.
Photomicrograph
in Biliary
of the
liver
Atresia
of some duct in
Fig.
105
in Case 7.
Fig.
10
Fig. 10. A graphic reconstruction branches of intrahepatic bile Case 3.
interlobular bile were moderately ducts indicated examined except in Case 6.
Bile Ducts
11
11. A graphic reconstruction of an intrahepatic bile duct in Case 5.
duct was clearly recognized in a portal tract. Hepatic cells degenerated. A macroserial reconstruction of intrahepatic bile that the main bile ducts were patent along the whole length at the porta heaptis (Fig. 10). Similar findings were observed
106
T. Chiba Case
at
5.
T.H.Y.,
5 months
some
of
drugs
during
Jaundice
had
University 100
The atresia
fistula
(Kasai
The
et
the
observed
fibrosis
lobules
with
shows
linking
considerably
E,
toward the
Fig. 12.
13.
Macroserial
pictures
is
sections
the
at
each
about
found
to
the
changing
liver
destroyed
in
5 of
and
.Th a main
no
is
about
2,500 ƒÊm.
B
was
duct
was
bile C can
of
,D,E be
Fig.
and seen
.C specimen.
d uct.
picture
Regenerative
which
lumen
L, liver
marked
hepatis
shown
in Case 5
duct;
bile
as
of the
13-A).
This size
because
13).
porta
bile ducts
H , heaptic Case
in
the
excretion
suggesting
(Fig.
from
bile
showed
(Fig.
seen
of
complicated
later
liver
inflammation. decrease
extrahepatic
aspects
mm
no
firm,
the
slide patient.
However,
months
other were
9
acute
completely
of the
of
cells
G, gallbaldder;
of show
tracts liver
in
and
bile duct;
Photomicrographs ese
duct
involved
linking
5 very
the
external
this
was
and
was
mg/ of
histological
necessary.
died
10.3
an
from
operation
examination
of
periphery
epithelial
, common Fig.
and
the
liver
a
g.
Tohoku
type
with
obstruction
the She
the
portal
bile
dilated
followed
after
The
took
3,600
to was
life.
shows
was
was
bilirubin of
cold
She
birth
removed
Intestinal
operation.
arrangment
intrahepatic
12
duct
common
admitted
jejunostomy
re-operation
autopsy,
with
day
Fig.
good. and
second
serum
68th
bile
Histological
irregular
an
out.
at
was
total
the
from pregnancy.
weight she
hepatic
occurred
At
of
The on
carried
frequently the
1972.
not
suffered
months
Body
extrahepatic
was
case
6
when
Double-Y
operation
cirrhosis.
portal
14, performed
the
first
after
liver
birth
was
of
cholangitis.
biliary
sickness.
1972)
cholangitis
ascending
of her
August
this
at
since
was
al.
of
periods
course
after
mother
exanthema
Kasai's ‡Vb.
postoperative days
was
In
on
operation
sections
ascending
13
both
was
macroserial
The and
continued
Hospital
ml.
biliary
23
female.
pregnancy,
et al.
The
distance
of
each
F. in
Intrahepatic
Bile Ducts
in Biliary
Atresia
107
108 F
T. Chiba
any
more.
The
indicated
a size
and
disappeared
at
In
more
peripheral
portions
hepatis.
were
present. to
the of
Severe have
Case
7.
was She
December was
3,600
1973
mg/100
total
The
serum
she
of
months paratively
and
and
complication
of
specimen
case,
inflammatory
preserved
reports
however,
these
authors,
Fig.
the been
bile
in
of the
published especially
of
liver the (Kasai Kasai's
of
and
ducts
spite
tree
(Fig
of
evidence
extrahepatic 1966;
.
Gross
classification
duct
1953) ,
. has
fistula
was and
However,
the
of
seen
in
at fresh
the
liver
(Fig
. 9). showed
but
liver
bile
severe
com
suggested
large
The
4 .5
was
proliferation
of 14).
a was
were
relatively
of
bile
revealed
examination
were
on
atresia
liver
findings
ductular
day
intestine
the
These
24th
.
strangulated
micro-abscesses
3 of
bilirubin
life
operation
.
at
disappeared
that
reconstruction
biliary in
after
Histological
bile
of
external
intestine.
fibrosis
the
serum
Jaundice days
case
weight
biliary
an
ducts
Hosptial
day the
However,
macroserial the
of
87th
revealed
cholangitis.
The
form
the
periportal
interlobular
structure
the type
perforation
Autopsy
ascending
throughout
have
no
moderate
Concerning
to
elastic.
was
changes.
normal
due
35
on
Total
with
range
birth
University
uneventful.
a normal
somewhat
acute
disclosed
this
within
was
operation.
there
on
this
cold
The
operation.
The
in
common
jaundice
porto-jejunostomy course
peritonitis first
from
Tohoku
ducts.
bile
the
obstruction
ducts
disease.
11
from
small
bile
Fig. abruptly
liver
intestinal
persistent
performed
the
sections,
this
in
hepatis
into
suffered
for
shown
porta
intrahepatic
for
clinic
bile
hepatic
was
the soft
tracts
operation
postoperative
diffuse
after
nearly
extrahepatic
bilirubin
died
portal
The
of
our
duct
following
Pediatrics,
to
the
macroserial
noticed
the
referred
ml.
of
drugs
parents to
Double-Y
performed.
In
and
obliteration
Kasai's ‡Va.
The
admitted
in
bile
centimeters
the
some
of
duct
mother
took
g.
bile
portion
several
obliterated Her
and
this
complicated
and
female.
was
25,
12.8
total
destroyed
pregnancy
patient
large
cholangitis
H.K.,
of
life.
comparatively
of
in
porta
months
sections
that
diminished
seemed
macroserial
et al.
showed
the
were
well
ducts
inflammation. biliary
atresia
, several
Nowadays
classification
generally
been
14. A graphic reconstruction of the mai T n bile ducts in Case 7. hese findings are similar to those of the normal intrahepatic bil
e ducts.
accepted.
by
Intrahepatic
Bile Ducts
in Biliary
Atresia
109
Furthermore, one of the authors (Kasai) described the histological findings of macroserial sections of extrahepatic bile ducts in his series of 68 cases and concluded that the obliterated portion of the bile duct showed similar histological features regardless of type and subtype of the lesion, or size of ducts (Kasai 1974). He also reported the histological findings of the bile duct in the region of porta hepatis and indicated a close correlation between size of the bile duct at the porta hepatis and postoperative excretion of bile. There have been several reports of microscopic study on surgical or autopsy specimens of the liver and a few reports on histological reconstruction of intrahepatic bile ducts (Oh-i et al. 1969; Landing et al. 1973). From reconstruction studies it has been shown that main interlobular bile ducts are usually open in the specimen taken from the peripheral portion of the liver. The study, however, has rarely been done on the patency of the intrahepatic biliary tree from the porta hepatis to the periphery of the liver of biliary atresia. The patency of bile ducts within the liver can be conjectured from clinical experi ences in that active excretion of bile has been observed after bile duct-intestinal anastomosis in correctable type and after hepatic porto-enterostomy in non-cor rectable type of biliary atresia. The result of the present study showed that the intrahepatic bile ducts were patent up to their peripheral portion in 6 of 7 cases of biliary atresia examined, regardless of the gross findings of extrahepatic bile ducts. Many anastomoses between main bile duct and proliferated ductules were confirmed by Oh-i et al, (1969) by means of histological reconstruction of interlobular bile ducts. It seems that bile draining ducts in the liver are patent at least in the early day of life. Some changes may occur, however, within the liver in the late stage which will result in obliteration of intrahepatic bile ducts. Bile plugs may be formed in intralobular bile ducts which obliterate bile flow in the tract. Progressive portal fibrosis may cause atrophy of interlobular bile ducts which may subsequently disappear. In our Case 5, it seems probable that severe ascending cholangitis complicated after successful operation destroyed the main bile ducts which might be finally obliterated by fibrous tissue. Considering the results of the present study and reviewing the literature, it is concluded that operation should be done in the early days of life and that comparatively deeper dissection into the liver is preferable. References
1)
Gross, R.E. (1953) Obstructive jaundice in infancy. In: The Surgery of Infancy and Childhood, edited by R.E. Gross, Saunders Company, Philadelphia & London, pp. 508-523. 2) Healey, J.E. (1953) Anatomy of the biliary ducts within the human liver. A.M.A. Arch. Surg., 66, 599-616. 3) Kasai, M. (1966) Surgery of liver and bile duct. In: Gendai Shonigaku Taikei Vol. 16 (Jap.), edited by Ts. Arakawa, T. Nagayama & N. Yamada, Nakayama Co., Tokyo, pp. 104-139. 4) Kasai, M. (1974) Treatment of biliary atresia with special reference to hepatic porto enterostomy and its modifications. Prog. Pediat. Sury., 6, 5-52.
110
T. Chiba
et al.
5) Kasai, M., Asakura, Y., Suzuki, H. & Ohashi, E. (1972) Modification of hepatic porto-enterostomy to prevent postoperative ascending cholangitis. In: Proceedings of the Fifth Annual Meeting of the Pacific Association of Pediatric Surgeons, edited by K. Suruga PAPS Committee, Tokyo, p. 10. 6) Landing, B.H., Wells, T.R., Reed, G.B. & Narayan, M.S. (1973) Disease of the bile ducts in children. In: The Liver, edited by B.H. Landing; The Williams & Wilkins Co. Baltimore, pp. 480-509. 7) Oh-i, R., Kasai, M. & Takahashi, T. (1969) Intrahepatic biliary obstruction in congenital bile duct atresia. Tohoku J. exp. Med., 99, 129-149. 8) Sawaguchi, S., Nakajo, T., Hori, T., Harada, Y. & Ohbe, Y. (1968) Staged reconstruc tion of biliary tract for congenital bile duct atresia. Jap. J. Surg. (Jap.), 69, 13171318. 9) Suruga, K. (1970) Operations for biliary atresia. Shijutsu (Jap.), 24, 543-549.
J. exp.
Med.,
1975,
115, 99-110
Reconstruction of Intrahepatic Congenital Biliary Atresia
Bile Ducts
TSUNEO CHIBA, MORIO KASAI and
in
NOBUAKI SASANO*
The Second Department of Surgery and The Second Department of Pathology*, Tohoku University School of Medicine, Sendai
CHIBA, Ducts
in
T.,
KASAI,
Congenital
-Macroserial 7
cases
biliary
according
studies,
it
through
the
performed
was
one
duct
and
to
tion
of
be
has
also In
in of
with
cause seen view
biliary
intrahepatic
of
and
a number
of
atresia.
As
of
these
infants facts
the
severe or
with
this
operation
ducts;
usually
small
ducts. tract
These
one
of an
case
many of
the
cholangitis of
intrahepatic
without early
results in
ascending
disease
around
obtained
in
of
patent
portal
duct. was
in
cases
a network
biliary
ascending
made 4
bile
disappearance
atresia. -congenital bile
main bile
observed
of
destruction
older
of
a
99-110
reconstruction
are
make
the
was
extrahepatic of
Bile
(2),
and
ducts
the
ductules
excretion
ducts
of these
ductules
with
active
of
in
results
of
115
type ‡U
bile
atresia
ducts
biliary
the
Intrahepatic
1975, bile
of
interlobular
type
of
Med.,
1 case
From
main
that
exp.
intralobular I,
complication
important
cholangitis.
recommended struction
an
Reconstruction J.
communications
fact
postoperative
which
type
that
some the
main
of
bile
disclosed
have
the
the
of
with
series,
ducts,
the of
patients
present
cases
that
case
N.
Tohoku
classification.
reconstruction
postoperative
bile
Kasai's
regardless
compatible
seemed
2
confirmed liver
in
main
were
SASANO,
of
atresia; to
microserial
the
and Atresia.
reconstruction of
type ‡V
A
M.
Biliary
stage atresia;
complica of
life
is
recon
cholangitis
The pathogenesis of biliary atresia is not known. Although many kinds of study have been performed up to the present, the true cause of the disease is not clear. Recently, it has been reported by several authors that this disease may result from some inflammatory process of the liver and biliary tract during intrauterine life. Knowledges about the pattern of the bile ducts seem to be a prerequiste for studying the cause of this disease. The form of the intrahepatic biliary tree can be demonstrated by x-ray films with contrast medium, a cast using resin, and histological reconstruction. The normal structure of intrahepatic biliary tree was previously described by Healey (1953). In the liver of biliary atresia, however, visualization of the bile ducts with contrast medium or resincast is practically impossible. Therefore, the technique of histological reconstruc tion is required for demonstration of bile ducts in the liver. There have been some reports on this subject, but most of them are concerned with the structure of bile ducts and ductules in the peripheral liver specimen. The present report describes the study of intrahepatic main bile ducts extending from the porta hepatis to the periphery of the liver in biliary atresia. Received
for publication,
November
19, 1974 99
100
T. Chiba
et al.
MATERIALS AND METHODS Autopsy the
was
past
were
four
obtained
specimen
was
cularly to of
an
the
porta
to
2500 ƒÊm. the
for
were
agent.
In
(Fig.
was
fixed
1).
in
6
cases,
case ether
xylene
(Case
and
imbedding
2),
in
liver
numbers
were
paraffin
was
used
written
solvent for
paraffin
blocks
were
to
serial
was the
each
block
alcohol,
with
the
these
dehydrating
imbedding).
solvent
after the
blocks
2000
thickness
tissue
with
(paraffin
cutting perpendi
about
on of
In
the
the
infiltration
process
without
a
perpen
and
block
After
wooden
liver
cases
surface
paraffin
imbedding).
attached
tissue
miscible
solvent for
6
dehydration is
study
abdomen,
fixation, in
the
during
the
depending
on
which
used
(celloidin-paraffin
tissue
each
hours present
the of
After
Following
was
periphery
variable,
the
from
hepatis
of
was
direction.
the
porta
thickness block
the
the
of
removed
formalin.
to The
3 postmortal
materials
was to
neutral
tissue
and
within The
hepatis
10%
chloroform
celloidin
these
the porta
1 case.
site to
the
the
atresia
Hospital.
After
and
the
biliary
horizontally
of
Marks
of
cases.
slicer
transferred
remaining with
from
number
confirmation
blocks
bloc
hepatis
The
liver
en
electric
of
University
7
specimen
with
7 cases
Tohoku
these
excised
The
made
in
at
from
dicularly. was
performed
years
of
paraffin
distortion
of
the
direction.
Fig. 1. Serial of
sections
Case
2.
Each
section
other
was
with
elastica-Masson
such
as
eosin.
After
the
macroserial was
similar
in
cases,
about
also
6 ƒÊm
and
the
staining,
All
a
6 ƒÊm
stain
vessels
tion.
tract
of
In
the
A part of serial tissue blocks of the liver (Case 7).
made technique.
and
graphic in
in for
like. all
ducts
addition
thickness
were
10 thickness.
good
sections
A
obtained
large
were
the
projected
within
macroserial
of
the of
large
the
bile
reconstruction
every
the
were paper
and of
large
ductules bile
in ducts
tissues
hematoxylin
high
were
stained
other
with
under
block.
were
from
stained
demonstrated
ducts
blocks
paraffin
sections
cholangioles
tracing
tract
celloidin-paraffin
from of
sections on
portal
every
majority of
number
reconstruction to
from
were
discrimination
A small
ductules
prepared
sections
magnifica
traced a in
small Case
.
Thus portal 2 with
Intrahepatic
Bile Ducts
in Biliary
Atresia
101
RESULTS AND DISCUSSION According bile
duct
III,
in
to
were
6 and
were
cases
are
to
Case
1.
Y.M.,
total
the
of
duodenum
was
obstruction made
was
was
not
after
operation.
was
completely
and
Histologically proliferation
canaliculi
and in
bile
lobules.
comparatively (Fig.
many
large 4)
bile
2),
the
duct
found
cut
surface
that
Photomicrograph
found. the
main
pregnancy
for
not
Hospital
weighed
400
g,
periportal
zone
were
in
ductules adjacent
The
bile
was
only
18
days duct
firm
and
were
tracts
and
the
porta
hepatis,
duct
liver specimen
in
intrahepatic
was
open
in Case 1.
in
moderate cells
portal
of
the
bile was
Hepatic
reconstruction
interlobular
of the peripheral
to
of
died
fibrosis
in
type
common which
seen.
the with
postoperative
She the
the
on
duct
The
of
on
and
performed
bile
decrease.
g. was
communication
patient.
the
2,850 She
The
portion
in
was
bilirubin
was no
common
the
distal
marked
were
was
other
interesting
University
and
with
did the
periportal
plugs
On
demonstrated
Fig. 2.
the
as type
the
jaundice.
operation
of
liver
(Fig. in
2,
and
birth
cholangiography.
bilirubin
The
Case
two
of at
test
dilated
fistula
that
toxemia
Tohoku
The
condition
serum
extrahepatic
male and
weight
Schmidt's
was
external
revealed
obliterated.
degenerated
ducts
good
duct
general
in
6 was
neonatal
Surgery,
intraoperative
An
poor
Autopsy
consistency. ductular
Ia.
the
type ‡Ub
from
after
ml.
bile
of the
types
Body
negative
mg/100
as Case
various
normal.
of
by
7.
suffered
was
14.6
4,
and
findings
:
mother
showed
disclosed
of
5
following
common
Kasai's
because
course
The
gross
1 and
3,
manifested
stool
was
life.
Cases
Department
The
bilirubin
day
the
delivery
Second
1966),
representing
continuously
1971.
serum
228th
in Cases
Her
the
been
to
in
female. but
18,
Ia in
cases
described
had
admitted
the
be
(Kasai
type
type ‡Vb Three
pregnancy,
January
as
as
female.
Jaundice
classification
classified
Case
cases
late
Kasai's
bile a bile
along
its
102
T. Chiba
Fig. 3.
Photomicrograph
Fig. 4. A graphic reconstruction of some branches of intrahepatic bile duct in Case 1.
et al.
of the liver
in Case 2.
Fig. 5. A graphic reconstruction of some branches of intrahepatic bile duct in Case 2.
whole length through the liver. The reconstructed bile duct seemed to be the medial superior duct of the left lobe. The reconstructive findings of a bile duct in Case 4 which died 6 months of life were similar to those in Case 1. Case 2. M.J., female. Her mother was in good health during the pregnancy. Body weight at birth was 3,000g. Persistent jaundice appeared after the neonatal jaundice once disappeared. She was admitted to our clinic on January 11, 1971.
Intrahepatic
Fig.
Total
serum
89th
day
life.
be
After
jaundice
the
However,
liver
and
weighed
350
disclosed
feration
was
with
that
ducts
and
the
periphery Case
3.
birth to
19,
the
on
duct classified
bile
g.
al.
The
open
study
the
main
the
the
proli
microscopic is
consistent duct
duct, of
their
of
draining
main
along
existed.
Ductular
finding
reconstruction
hemor
kidneys
shows This
(1969).
were
both
3).
6
block.
surrounded
ducts
subsequent that
Histological
Fig.
one
macroserial
of
life
duct
Kasai's ‡Vb.
suffered
was
occasionally
intrahepatic
whole
were
fibrous, Fig.
7
10
bile
length
to
the
while shows
the a
left
ml.
The
hepatic
hepatic
bile
ducts.
common
was of
on
operation
duct,
duct slide
was
Hospital
extrahepatic
right
histological
Body She
University
of
The
pregnancy.
disappear.
mg/100
obliteration
lumen.
of
not
Tohoku was
a total a small
toxemia did
Surgery,
bilirubin
revealed with
from
jaundice of
serum
atrophic
cystic
mother Neonatal
Department total
day
was
as
The
Her
Second
88th
and
et
ductules shows
2,700
The
gallbladder
Oh-i
5
female. was
1971.
performed
in
al. and
liver.
K.K.,
at
July
liver.
the
by of
Fig.
zones.
ductules
and
(Fig.
et
fistula
revealed of
firm. fibrosis
periportal
and
number it.
same
of
admitted
a
relatively
periportal
(Sawaguchi
Autopsy swelling
the
contrast type ‡Ub).
external
hematemesis
and
the
(Kasai's
performed
the
atretic,
and
duct
on
were
dilated
this
of
performed
duct
bile
day.
was
the
duct described
with
of
weight
in
bile
previously
connecting
which
was
were
was
lungs
in Case 2.
cystic
through
died
both
irregular
noticed of
preserved
g,
marked
reconstruction
she
of
and
fistula
postoperative
edema
tract
intrahepatic
excreted
103
operation
duct
radicles
external
38th
The
bile
the
bile
the
ml.
into
Atresia
of the portal
hepatic
with
on
pneumonia
liver
and
both
operation,
edema
rhagic
hepatic
common
injected
diminished.
pulmonary
The
mg/100
the and
easily
in Biliary
reconstruction
14.6
porto-jejunostomy
1968).
The
duct
could
Hepatic
was Although
hepatic
medium
A graphic
bilirubin of
common
6.
Bile Ducts
not
macroserial
seen
inn
T. Chiba
et al.
Fig. 7. Macroserial sections of the extrahepatic bile ducts in Case 3. duct; G, gallbladder; H, hepatic duct (right); L, liver specimen.
Fig. 8.
Photomicrograph
of the
liver
C, common bile
in Case 3.
sections of the extrahepatic bile duct removed from this patient. Hepatic porto jejunostomy with Witzel-type fistula was performed. The tube jejunostomy was excised and double-barreledjejunostomy was made 10 days after the first opera tion because intestinal decompressionthrough the tube was inadequate (Suruga 1970). After the second operation the general condition of the patient became worse and died of the anastomotic leakage 67 days after the first operation. The liver weighed 500 g, which was firm in consistency at autopsy. As shown in Fig. 8, the liver histologically showed moderate ductular proliferation. An
Intrahepatic
Fig. 9.
Fig.
Photomicrograph
in Biliary
of the
liver
Atresia
of some duct in
Fig.
105
in Case 7.
Fig.
10
Fig. 10. A graphic reconstruction branches of intrahepatic bile Case 3.
interlobular bile were moderately ducts indicated examined except in Case 6.
Bile Ducts
11
11. A graphic reconstruction of an intrahepatic bile duct in Case 5.
duct was clearly recognized in a portal tract. Hepatic cells degenerated. A macroserial reconstruction of intrahepatic bile that the main bile ducts were patent along the whole length at the porta heaptis (Fig. 10). Similar findings were observed
106
T. Chiba Case
at
5.
T.H.Y.,
5 months
some
of
drugs
during
Jaundice
had
University 100
The atresia
fistula
(Kasai
The
et
the
observed
fibrosis
lobules
with
shows
linking
considerably
E,
toward the
Fig. 12.
13.
Macroserial
pictures
is
sections
the
at
each
about
found
to
the
changing
liver
destroyed
in
5 of
and
.Th a main
no
is
about
2,500 ƒÊm.
B
was
duct
was
bile C can
of
,D,E be
Fig.
and seen
.C specimen.
d uct.
picture
Regenerative
which
lumen
L, liver
marked
hepatis
shown
in Case 5
duct;
bile
as
of the
13-A).
This size
because
13).
porta
bile ducts
H , heaptic Case
in
the
excretion
suggesting
(Fig.
from
bile
showed
(Fig.
seen
of
complicated
later
liver
inflammation. decrease
extrahepatic
aspects
mm
no
firm,
the
slide patient.
However,
months
other were
9
acute
completely
of the
of
cells
G, gallbaldder;
of show
tracts liver
in
and
bile duct;
Photomicrographs ese
duct
involved
linking
5 very
the
external
this
was
and
was
mg/ of
histological
necessary.
died
10.3
an
from
operation
examination
of
periphery
epithelial
, common Fig.
and
the
liver
a
g.
Tohoku
type
with
obstruction
the She
the
portal
bile
dilated
followed
after
The
took
3,600
to was
life.
shows
was
was
bilirubin of
cold
She
birth
removed
Intestinal
operation.
arrangment
intrahepatic
12
duct
common
admitted
jejunostomy
re-operation
autopsy,
with
day
Fig.
good. and
second
serum
68th
bile
Histological
irregular
an
out.
at
was
total
the
from pregnancy.
weight she
hepatic
occurred
At
of
The on
carried
frequently the
1972.
not
suffered
months
Body
extrahepatic
was
case
6
when
Double-Y
operation
cirrhosis.
portal
14, performed
the
first
after
liver
birth
was
of
cholangitis.
biliary
sickness.
1972)
cholangitis
ascending
of her
August
this
at
since
was
al.
of
periods
course
after
mother
exanthema
Kasai's ‡Vb.
postoperative days
was
In
on
operation
sections
ascending
13
both
was
macroserial
The and
continued
Hospital
ml.
biliary
23
female.
pregnancy,
et al.
The
distance
of
each
F. in
Intrahepatic
Bile Ducts
in Biliary
Atresia
107
108 F
T. Chiba
any
more.
The
indicated
a size
and
disappeared
at
In
more
peripheral
portions
hepatis.
were
present. to
the of
Severe have
Case
7.
was She
December was
3,600
1973
mg/100
total
The
serum
she
of
months paratively
and
and
complication
of
specimen
case,
inflammatory
preserved
reports
however,
these
authors,
Fig.
the been
bile
in
of the
published especially
of
liver the (Kasai Kasai's
of
and
ducts
spite
tree
(Fig
of
evidence
extrahepatic 1966;
.
Gross
classification
duct
1953) ,
. has
fistula
was and
However,
the
of
seen
in
at fresh
the
liver
(Fig
. 9). showed
but
liver
bile
severe
com
suggested
large
The
4 .5
was
proliferation
of 14).
a was
were
relatively
of
bile
revealed
examination
were
on
atresia
liver
findings
ductular
day
intestine
the
These
24th
.
strangulated
micro-abscesses
3 of
bilirubin
life
operation
.
at
disappeared
that
reconstruction
biliary in
after
Histological
bile
of
external
intestine.
fibrosis
the
serum
Jaundice days
case
weight
biliary
an
ducts
Hosptial
day the
However,
macroserial the
of
87th
revealed
cholangitis.
The
form
the
periportal
interlobular
structure
the type
perforation
Autopsy
ascending
throughout
have
no
moderate
Concerning
to
elastic.
was
changes.
normal
due
35
on
Total
with
range
birth
University
uneventful.
a normal
somewhat
acute
disclosed
this
within
was
operation.
there
on
this
cold
The
operation.
The
in
common
jaundice
porto-jejunostomy course
peritonitis first
from
Tohoku
ducts.
bile
the
obstruction
ducts
disease.
11
from
small
bile
Fig. abruptly
liver
intestinal
persistent
performed
the
sections,
this
in
hepatis
into
suffered
for
shown
porta
intrahepatic
for
clinic
bile
hepatic
was
the soft
tracts
operation
postoperative
diffuse
after
nearly
extrahepatic
bilirubin
died
portal
The
of
our
duct
following
Pediatrics,
to
the
macroserial
noticed
the
referred
ml.
of
drugs
parents to
Double-Y
performed.
In
and
obliteration
Kasai's ‡Va.
The
admitted
in
bile
centimeters
the
some
of
duct
mother
took
g.
bile
portion
several
obliterated Her
and
this
complicated
and
female.
was
25,
12.8
total
destroyed
pregnancy
patient
large
cholangitis
H.K.,
of
life.
comparatively
of
in
porta
months
sections
that
diminished
seemed
macroserial
et al.
showed
the
were
well
ducts
inflammation. biliary
atresia
, several
Nowadays
classification
generally
been
14. A graphic reconstruction of the mai T n bile ducts in Case 7. hese findings are similar to those of the normal intrahepatic bil
e ducts.
accepted.
by
Intrahepatic
Bile Ducts
in Biliary
Atresia
109
Furthermore, one of the authors (Kasai) described the histological findings of macroserial sections of extrahepatic bile ducts in his series of 68 cases and concluded that the obliterated portion of the bile duct showed similar histological features regardless of type and subtype of the lesion, or size of ducts (Kasai 1974). He also reported the histological findings of the bile duct in the region of porta hepatis and indicated a close correlation between size of the bile duct at the porta hepatis and postoperative excretion of bile. There have been several reports of microscopic study on surgical or autopsy specimens of the liver and a few reports on histological reconstruction of intrahepatic bile ducts (Oh-i et al. 1969; Landing et al. 1973). From reconstruction studies it has been shown that main interlobular bile ducts are usually open in the specimen taken from the peripheral portion of the liver. The study, however, has rarely been done on the patency of the intrahepatic biliary tree from the porta hepatis to the periphery of the liver of biliary atresia. The patency of bile ducts within the liver can be conjectured from clinical experi ences in that active excretion of bile has been observed after bile duct-intestinal anastomosis in correctable type and after hepatic porto-enterostomy in non-cor rectable type of biliary atresia. The result of the present study showed that the intrahepatic bile ducts were patent up to their peripheral portion in 6 of 7 cases of biliary atresia examined, regardless of the gross findings of extrahepatic bile ducts. Many anastomoses between main bile duct and proliferated ductules were confirmed by Oh-i et al, (1969) by means of histological reconstruction of interlobular bile ducts. It seems that bile draining ducts in the liver are patent at least in the early day of life. Some changes may occur, however, within the liver in the late stage which will result in obliteration of intrahepatic bile ducts. Bile plugs may be formed in intralobular bile ducts which obliterate bile flow in the tract. Progressive portal fibrosis may cause atrophy of interlobular bile ducts which may subsequently disappear. In our Case 5, it seems probable that severe ascending cholangitis complicated after successful operation destroyed the main bile ducts which might be finally obliterated by fibrous tissue. Considering the results of the present study and reviewing the literature, it is concluded that operation should be done in the early days of life and that comparatively deeper dissection into the liver is preferable. References
1)
Gross, R.E. (1953) Obstructive jaundice in infancy. In: The Surgery of Infancy and Childhood, edited by R.E. Gross, Saunders Company, Philadelphia & London, pp. 508-523. 2) Healey, J.E. (1953) Anatomy of the biliary ducts within the human liver. A.M.A. Arch. Surg., 66, 599-616. 3) Kasai, M. (1966) Surgery of liver and bile duct. In: Gendai Shonigaku Taikei Vol. 16 (Jap.), edited by Ts. Arakawa, T. Nagayama & N. Yamada, Nakayama Co., Tokyo, pp. 104-139. 4) Kasai, M. (1974) Treatment of biliary atresia with special reference to hepatic porto enterostomy and its modifications. Prog. Pediat. Sury., 6, 5-52.
110
T. Chiba
et al.
5) Kasai, M., Asakura, Y., Suzuki, H. & Ohashi, E. (1972) Modification of hepatic porto-enterostomy to prevent postoperative ascending cholangitis. In: Proceedings of the Fifth Annual Meeting of the Pacific Association of Pediatric Surgeons, edited by K. Suruga PAPS Committee, Tokyo, p. 10. 6) Landing, B.H., Wells, T.R., Reed, G.B. & Narayan, M.S. (1973) Disease of the bile ducts in children. In: The Liver, edited by B.H. Landing; The Williams & Wilkins Co. Baltimore, pp. 480-509. 7) Oh-i, R., Kasai, M. & Takahashi, T. (1969) Intrahepatic biliary obstruction in congenital bile duct atresia. Tohoku J. exp. Med., 99, 129-149. 8) Sawaguchi, S., Nakajo, T., Hori, T., Harada, Y. & Ohbe, Y. (1968) Staged reconstruc tion of biliary tract for congenital bile duct atresia. Jap. J. Surg. (Jap.), 69, 13171318. 9) Suruga, K. (1970) Operations for biliary atresia. Shijutsu (Jap.), 24, 543-549.
