" no
matter
What
he
or
she
\\;ll
~
facing
the
medical
have professors
it,
Itors,
or
physician
practiced
medicin~
It
the
practice
of
)gram, undertaken
ion, can do
nothing
I broken image. It
before entering a
n
the
time
of
tho~
Ictice of medicine
s where they
fusi
t
that
the
products
,ed
physicians
whu
n
at
the
medical
"EN,
JR,
MD,
PHD
a
impact on special-
::ation
is in danger
nority. Therefore,
,ew
proposals that
.re physician
from
ms
introduced
bv
! College, Dnive;.
:re
Dr
Griffin
that
posals to improve
medical education
mingo
o
MD,
MPH,
MSC
Education
iation
I
L
_
~_~I~.-
_____________________
_
Jriginal
Articles
-
Liver Transplantation for
Polycystic Liver Disease
Thon',
s
E.
Starzl,
MD,
PhD; Jorge Reyes,
MD;
Andreas Tzakis,
MD;
Luis Mieles,
MD;
5atoru
Thdo,
MD;
Robert Gordon,
lID
• Four
fema~e
pat~ents
with severe complications of polycys·
tie
liver
d~sease
were treated
with
liver replacement; two
pat~ents
were
a~so
given kidneys
from
the~r
liver
donors.
All four of the
petlents
were
suffer~ng
from extreme fatigue. Three
of
the
rec~p~·
enls
have survived
for
8, 11,
and
60
months
with
normal liver
funct~on
and present good health. The
fourth
pat~ent
recovered
trom
a
IIver-k~dney
transp~antation,
but
5
months
~8ter,
fu~mln8nt
hepat:c
failure
deve~oped
~n
this
patient
due
to
hepatlt~s
B virus, .
and
~:e
d~ed
d
..
p~te
emergency hepatic
retr8nsp~antatlon.
(Arch
Surg.
1(,90;125:575-577)
M
OSt
patients with polycystic liver disease
bear
a heavy
but nonlethal burden. Hepatic
failure is
unusual.1,2
Be-
tween
half' and two thirds
2
of patients
with
the
adult autoso-
mal
dominant disorder also have polycystic disease of the
kidney.
Before
the
availability of tlialysis and kidney trans-
plantation,
renal failure was a common cause of death.
Now
that
renal disease can
be
treated
effectively, more patients
can
be
expected to survive long enough
to
experience hepatic
rom(
;cations.'
Th,
nature and seriousness of the hepatic complications,
..-hich
are largely caused by mass effects, have been empha-
sized
increasingly in
recent
reports. U Although many pallia-
tivp
procedures have been proposed,·
these
operations are of
questionable
value and
are
excessively dangerous unless
there
are "dominant"
or
regional cysts. U We
report
here the
first
use, to our knowledge, of total hepatectomy and liver
transplantation for the
treatment
of polycystic liver disease in
four
patients
who
also had polycystic kidney disease.
Con-
tIlmitant
renal transplantation was performed in two of the
four
F·
'er recipients.
PATIENTS
AND METHODS
Case Material
The
four female recipients were aged
37
to
57
years
(Table).
4';11ldice,
hypoalbuminemia, clotting disorders, and other laboratory
fll~ence
of hepatic dysfunction
"'ere
not present.
However,
one
!Qtient
had esophageal varices,
and
two patients had ascites.
Three
of
the
four
patients had pain from the huge liver masses (Figure),
and
t\\'o
patients were addicted to narcotics (Table).
,
Significant
symptoms had been present for 3 to
13
years
(Table).
~.
four
patients complained
of
shortness
of
breath and/or extreme
tlgu.
0 The exhaustion was so profound
that
the four patients
had
!'.oPPE.;
professional or domestic
'Ili"Ork
and were confined to bed most
-----~-------------------------------------
ACCepted
for publication October 25,
1989.
l'
From
the Department
of
Surgery, l"ni\'ersity Health Center of Pittsburgh,
.
Illversity
of Pittsburgh (Pa) School
~
Medicine, and the Veterans
Admini8-
'tltion
Medical
Center, Pittsburgh.
PL
h
Reprint
requests to Department
~
Surgery, FaIk Clinic.
3601
Fifth Aft,
ttsburgh.
PA
15213
(Dr
StarzI).
of
the time. Patient 4 <Table) whose main complaint
was
that she
was
dying
of
exhaustion had respiratory insufficiency,
and
she eventually
required ventilatory
support
until a liver
could
be
found.
This
same
patient
had
undergone a
left
transverse colostomy and
cecostomy
1
year previously because of colonic obstruction and toxic
megacolon.
Liver
volume
was
estimated with computed tomographic scans'in
two patients
to
be
7120 and
12
790
mL (Table
~
It
was
too
inconvenient
and uncomfortable to
attempt
these measurements
in
the other two
patients.
Patient
3
(Table)
had undergone a right hepatic lobectomy
and
cyst
fenestration
in
1980,
"ith
a consequent reduction in the hepatomega-
ly
and symptomatic relief. However, the liver
slowly
enlarged
back
to
and beyond its original size (Figure, at right). The cysts were present
throughout the liver (Figure)
in all
of
the patients.
All four
of the patients had polycystic renal disease.
Two
of
the
four
patients
had
slightly eltvated serum creatinine concentrations
and
subnormal creatinine clearances of 0.50 to
0.58
mLls
(Table).
Surgical
Procedures
The orthotopic
liv~r
transplantations were performed by
using
standard technjques,' with an estimated
blood
loss
of
4 to
45
L.
The
most serious bleeding was
in
patient 3 (Table)
who
had
undergone a
right hepatic lobectomy plus cyst fenestration 8 years
previously.
The liver graft did not function well, necessitating retransplantation
11
days later.
In patient
4 (Table),
the
previously placed colostomy
and
cecos-
tomy were
closed
at
the
time of
transp~antation.
Numerous ulcer·
ations
of
the stretched and necrotic anterior abdominal
wall
in
this
patient were eliminated by excising a ""ide strip
of
skin and subcuta-
neous tissue
from
the xiphoid process to the pubis.
Patients 1 and
4 (Table) were given a kidney from their liver
donor.
The degree
of
renal failure (Table)
would
not
have
justified
kidney
transplantation under nonnal circumstances.
However,
it
was
feared
that the subnormal renal function
would
preclude giving a
full
thera·
peutic dose
of
cyclosporine because
of
this drug's nephrotoxicity.
The
liver was transplanted
first
in
both patients,
followed
by the
kidney
transplantations only
after
the
conditions of the patients were stable.
Aftercare
The four patients required ventilatory support postoperatively
for
9,
2, IS, and
13
days. Baseline immunosuppression
was
with
cyclo-
sporine and steroids.
Two
patients also had supplemental therapy
with
OIIT3 and/or azathioprine.
RESULTS
Liver
Size
The excised livers weighed
4000
to
12
900 g (Table).
This
weight range was a
gross
underestimate of the actual weights
since a large amount
of
fluid was lost when the cysts were
ruptured during
the
hepatectomies or when the specimen
was
cut afterward.
The
heaviest surgical pathology specimen
(from patient
1,
Table) weighed 12900 g. The histopathologic
Commentary
~Ch
Surg-Vo~
125,
May 1990
Polycystic Liver Disease -
Starz~
el
aI
575
----
-.,-r,
' 1---
, I
. I
.'
..
-,
r
J:
C
Clinical
Findings in
Four
Patients
With
Polycystic Liver Disease'
Petlent
'ing:-
~a-:.€-
--------------------------------~---------------------------------
3
10131188,
11/11188
57
White
F
62
x
4
11/21/88
42
White
F
60
x
X-
i~
';ear,
::ely
',r,
~.
.:.a~::'~
.
71.
'
.:.-eC
h(
..
~:i\c
J
-.
X X
I.
=::==~----------.:.:..--------.-.:~--------~:-:----------~~-----I,~~~
~~::~------------------------~----------------~--------------------~------------------------~--~'----
;
~<~
::
~~~----------------------------------------------------------------------------------~----__
i
:ier.~
X :
"~
pn:'
X
-:
_:::t.S2~
~~=---------------------------------~-----------------------------------------.
.~fz
12
13 I
Cyst
drainage Cyst aspiration
(1960), cyst colostomy
and
"
~;,u-~:
drainage (1974),
cecostomy!
:':''"Ea:::
RHl and F !
',;"r.:.:
1-
________________________
...:(~19=80:!.)
____________
I
:lg-:.:
12 790
~,\iOE-
r-~~~~~~~~
_____
~~
_____
~~
_________
4~1~OO~
__________
~~~
__
I~~p,
576
61
X
:.""'~
144.9
;'.-15.
F
;::;.:r,! :
150
058
I
·
......
l.~
..
=-~--~--------------~~--~~------------~~----------------~.~------------------~~.~-----
-,
~
Arch
Surg
-
Vol
125.
May
1990
0.56
0.83'
~e::.s
-~"'f'.
Polycystic
Liver
[)iseraS8-~"".,
:-~-;.j
c.
:!.-2:!'
:-:~~E
('
;;::
k:::-
--:.c..-..;,.:
~.
~
..
a:.--:
.~.:
!J.
~~:.:~
.\:.
to)
";'';:
t
~~:
:-
1.:
~
':':<k;
..
.:...."t'
a:
~~~
-J:,t;r
:....:&.,
--'
._-~--
....
---.-r-----
..
----:J
11121188
42
'Nhite
F
60
x
x
x
findings
in
the
specimens were typical of polycystic liver
• I
disease.
Survival
Three
of
the
four recipients have
been
well from 8 months to
,vears postoperatively. Patient 4 (Table) recovered
com-
~l~tely
from a liver-kidney transplantation,
but
5 months
13ter.
she
experienced fulminant hepatic failure caused by
heps:
; tis B virus. She died 2 days
after
emergency liver
~transplantation.
The transplant hospitalization was for
35,
~,
71,
and
99 days. The longest hospitalizations were re-
quired
because of pneumonitis (patient 3, Table) and a postop-
erative
psychosis (patient
1,
Table).
Function
of
Grafts
x I
The
liver function has been normal in
the
surviving recipi-
x
"I
'
ents
and was normal for 5 months in
patient
4 (Table) until the
----_-1
onset
of acute hepatitis. The subnormal renal function in
_____
-1
patients
1 and 4
was
improved with the renal grafts (Table).
___
x
___
.J..J·
The
;'-eviously normal renal function was decreased in pa-
___
x
___
J :
tient:
2 and 3 (Table) who were given a liver only;
their
loss
of
J
renal
function
was
ascribed
to
cyclosporine nephrotoxicity.·
____
1_3
___
~J
COMMENT
Cyst aspiration
colostomy
and
Surgical complications of polycystic liver disease and ways
cecostomy
of
treating
these
have been reported from clinics with special
12790
1
~
~
0.58
0.83
s.p#.
f
:ally.
At
lepatic
expertise in hepatic disease.
I
,'.ID-a
Such complications were
thought
to
be
rare
until recently. The
study
by
Grunfeld
et
all
provided
a more realistic assessment of
the
hepatic risks to
these
patients
now
that
death from renal failure could be
fores'.
~.lled
so
effectively.
In
patients with renal polycystic
diseai~
who
were
undergoing dialysis
at
the
Hopital Necker,
Paris,
France,'
a hepatic origin was
the
leading cause of
death.
I
Findings
from subsequent
reports
from other cen-
ters
s
,
have confirmed
that
there is a small
subset
of high-risk
patients.
Initially,
it
was difficult for us
to
recommend such a drastic
solution
as
liver transplantation for patients with polycystic
liver
disease who typically have normal liver function. Liver
transplantation was not even considered until
1984,
when
another
patient
with polycystic disease was brought in des-
perat,:,
condition
to
the operating room for a combined liver
and
l>dney transplantation, only
to
die of a fatal pulmonary
I
embolus
before
either
organ could
be
transplanted. Instead,
,
~e
have
tried
in
past
years
to
reduce
the
hepatic mass in such
patients
with
a partial hepatectomy and with
the
fenestration
procedure, as originally described by Lin and colleagues.
II
Although
these
operations can relieve symptoms temporar-
ily,
usually
there
is little reduction in
the
hepatomegaly. I A
right
hepatic lobectomy and fenestration operation in our
patient
3 (Table) left so many adhesions
that
liver replace-
ment
nearly 8
years
later was extraordinarily difficult.
An
exceptionally conservative
attitude
is still warranted
about
liver transplantation or, for
that
matter, any other
operatIOn
for polycystic liver disease. The most common rea-
SOn
to go forv.'aTd could be a syndrome of lethal exhaustion.
The
diagnosis of this condition may depend more on common
~nse
and
longitudinal clinical observations
than
on sophisti-
cated
tests.
All four of our patients had reached
an
end
to
their
functional
lives because they could no longer
carry
the weight
of~heir
slowly enlarging livers. Three of
them
had intractable
ilam,
and two patients were narcotic addicts. Fatigue had
closed
off almost all activity, except
that
required to breath
~d
carry
out
other
basic bodily functions. Peltokallio" may
I
nave
s"en
patients
'with this kind of disability, and one patient
III
GrJnfeld and colleagues
'
series died of cachexia. The
com-
Plaints
in
our
four patients were eliminated with
the
removal
of
the
mass
and transplantation of a normal-sized organ.
ease-Starzfet
J
A.rct,Surg-vol125, May 1990
A
»
Weaning from ventilator support was possible in 2 to
15
days.
The
two
recipients who had become narcotic addicts never
again asked for
pain medications, even during the first post-
operative days.
The
patients
all regained a vigorous life-style,
and all remained well, except for
the
liver-kidney recipient
who
e..-.;perienced fulminant hepatic failure from hepatitis B
virus
after
5
months
and died despite emergency liver
retransplantation.
Whether
to provide a kidney
at
the same time as liver
replacement
in
patients
with polycystic disease of both organs
is a
matter
of
judgment.
Because
the
nephrotoxicity
of
cyclo-
sporine is
the
limiting factor in
the
dose of this drug,· subnor-
mal function of native kidneys
that
still may be life supporting
could make
it
impossible to give enough cyclosporine to pro-
tect
the
new liver.
It
was this consideration that prompted the
decision in two
of
our
four patients
to
transplant a kidney from
the
donor who also provided
the
liver. Under normal
circUl,1-
stances,
it
would have been too early in the course
of
the renal
failure
to
have
warranted
kidney grafting.
If
a decision is
taken
to
transplant a kidney, there are good
reasons
to obtain
the
kidney from
the
liver donor, especially
if
the
patient's
serum
contains
the
wide-ranging cytotoxic anti-
bodies
that
can
promptly
destroy renal homografts. The liver
is peculiarly
resistant
to this kind of antibody attack," and
once
the
hepatic
graft
is in place,
it
can remove or neutralize
the
donor-specific antibodies, thereby allowing a kidney from
the
same donor
ro
survive in
the
immunologically hostile
environment.
'6
Fbr
a
patient
who is highly sensitized, this
may
be
the
only opportunity to transplant a kidney with a
reasonable expectation of success.
This study was
supported
by
research
grantll from the
US
Department of
Veterans A1fairs, Washington, DC, and by projeet
grant
OK
29961
from
the
Nstionallmtitutes
of
Health
, Bethesda,
Md.
References
1. Dalgaard OA.
Bilateral
polycystic disease of the kidneys. Acta
Med
&and. 195i:8(suppl328):1-255.
2.
Griin!eld JP, AIbouze
G,
Jungers
P,
et
aI.
Liver changes
and
complica-
tions in aduh polycystic
kidney
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1985;14:1-20.
3.
van
Erpecurn KJ,
Janssens
AR,
ThrpstraJL,
Tjon
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Tham
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Highly
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Turnage
RH,
Eckhauser
FE,
Knol JA, Thompson
NW.
Therapeutic
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..nth
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Am
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1988;4:365-372.
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Obstructive
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and
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Am
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1988;83:93-96.
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Van Truel
DH,
Hagler
NG, Schade
RR,
et
aI.
In
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G<utroenlerol-
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1. 1985;88:1812-1817.
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StarzI
TE,
Iwatsuki
S,
Esquivel
CO,
et
aI.
Refinementll
in
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~
que
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Semin
Liver Dis.
1985;5:349-356.
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HK,Lewin
KJ. Massive hepatomegaly in adult polycystic liver b
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Am
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1988;12:321-324.
9.
Myers B,
Newwn
L,
Boshkos C,
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aI.
Chronic injury of human renal
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1988;
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10,
Henson SW,
Gray
HK,
Dockerty MB. Benign tumors
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11.
LloylWones W,
Mountain
Je,
Warren
KW.
Symptomatic non·psrasitic
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the
1Wer.
Br J Surg.
1974;61:118-123.
12.
Longmire WP, Mandiola
SA,Gordon
HE.
Congenital cystic disease
of
the
liver and biliary
system.
Ann
Surg.1971;174:7U-726.
13.
Lin
T'i,
Chen
ce,
Wang
SM.
Treatment
of non-parasitic cystic disease
of
the
liver: a
new
approach
to
therapy
"'~th
polycystic liver. Ann Surg.
1968;168:921-927.
14.
Peltokallio
V.
Non-parasitic
cystll
of
the
liver: a
clinical
study of
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cases.
Ann CltirGyntUrol.
1970;59:1-58.
15.
StarzI
TE,
Demetris
AJ,
'lbdo S,
et
aI.
Evidence for hyperacute rejection
of human
Ii'"l!r
grafts:
the
case
of
the
canary kidneys. Clin 7raMpwnt.
1989;3:37-48.
16.
Fung JJ, Griffin M, Duquesnoy R, Shaw B, Starzl TE.
Succeasful
sequential
Iner-kidney
transplantation
in a patient with prefonned lymphocy·
toxic antibodies.
7Tamplant Proc.
1987;19:767-768.
Polycystic
Liver
Disease-Starzl
at
aI
sn