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First description of the surgical anatomy of the cynomolgus monkey liver.

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American Journal of Primatology 71:400–408 (2009)
RESEARCH ARTICLE
First Description of the Surgical Anatomy of the Cynomolgus Monkey Liver
CORINNE VONS1, SYLVIE BEAUDOIN2,3, NADA HELMY1,4, IBRAHIM DAGHER1,4, ANNE WEBER4,
1,4
AND DOMINIQUE FRANCO
1
AP-HP, Department of Surgery, Antoine-Bécle`re Hospital, University Paris XI, Clamart, France
2
AP-HP, Department of Surgery, Saint-Vincent de Paul Hospital, Paris, France
3
Laboratoire d’anatomie et organogenèse, Universitè Paris V, Paris, France
4
Inserm U804, Bicêtre Hospital, Kremlin-Biceˆtre, Paris XI, France
No detailed description of nonhuman primate liver anatomy has been reported and little is known
about the similarity between such livers and human liver. The cynomolgus monkey (Macaca
fascicularis) was used to establish a preclinical model of genetically modified hepatocytes auto
transplantation. Here, we report information gleaned from careful observation and notes obtained from
59 female cynomolgus monkeys undergoing 44 anatomical hepatic resections, 12 main portal vein
division dissections and selective branch ligations, and 46 portographies. Additionally, three anatomical
liver dissections after total resection at autopsy were performed and served to confirm peroperative
observations and for photography to provide illustrations. Our results indicate that the cynomolgus
monkey liver has four lobes: the median (the largest), the right and left lateral, and the caudate lobes.
In 60% (N 5 20) of individuals the portal bifurcates into right and left portal veins, in the remaining
40% (N 5 14) the portal vein trifurcates into right anterior, right posterior, and left portal veins. The
anatomy and branching pattern of the hepatic artery and bile ducts closely follow those of the portal
branches. Functionally, the cynomolgus monkey liver can be divided into eight independent segments.
Thus, we report the first detailed description of the hepatic and portal surgical anatomy of the
cynomolgus monkey. The cynomolgus monkey liver is more similar to the human liver than are livers of
any small or large nonprimate mammals that have been described. Am. J. Primatol. 71:400–408, 2009.
r 2009 Wiley-Liss, Inc.
Key words: liver; anatomy; cynomolgus monkey
INTRODUCTION
Liver anatomy in dogs and pigs has been
extensively described [Court et al., 2003; Kamimura
et al., 1997; Peng et al., 2005; Van Minh, 1996;
Veeragandham et al., 1993]. However, no detailed
description of nonhuman primate liver anatomy has
been reported and although the liver anatomy of
nonhuman primates may be closely related to that of
humans little is known about the similarities.
Previous research on nonhuman primate liver
anatomy has mostly documented external liver
morphology [Houssin et al., 1988; Miller et al.,
1978; Voss, 1970].
In 1995, we decided to establish a preclinical
model in a nonhuman primate with the goal of
treating children suffering from inherited metabolic
liver disease [Andreoletti et al., 2001; Vons et al.,
2001]. We chose to utilize a nonhuman primate for
this purpose rather than other large mammals, for
example pigs, with the hypothesis that it may be
more similar to human. The cynomolgus monkey
(Macaca fascicularis, also known in the literature as
M. irus or the crab-eating monkey) was chosen
because the animal laboratory of our institute has
r 2009 Wiley-Liss, Inc.
extensive experience in rearing this species. This
monkey has the advantage of a small size, unlike the
baboon utilized by Grossman [Grossman et al.,
1992], facilitating manipulation. Moreover, relatively
small numbers of hepatocytes (600 106) were
isolated from the left hepatic lobe after resection
(20% of total liver but only 40–60 g per animal).
These hepatocytes required subsequent genetic
modification in vitro before autotransplantation.
However, because they are small, the cynomolgus
monkey has the disadvantage of poor tolerance to
prolonged anaesthesia and a particularly high risk of
peroperative hypothermia. Therefore, we performed
hepatic surgery in a facility already specialized in the
Contract grant sponsors: AFM (Association Franc- aise contre les
Myopathies); Inserm.
Correspondence to: Corinne Vons, AP HP, Department of
Surgery, Jean Verdier Hospital, Avenue du 14 Juillet, 93143
Bondy Cedex, France. E-mail: [email protected]
Received 7 May 2008; revised 20 December 2008; revision
accepted 26 December 2008
DOI 10.1002/ajp.20667
Published online 4 February 2009 in Wiley InterScience (www.
interscience.wiley.com).
Anatomy of the Cynomolgus Monkey Liver / 401
use of monkeys. Previously available information
about the anatomy of the cynomolgus monkey liver
was limited. Over the last 10 years, we have
performed more than 100 surgical procedures involving the liver of this species, including 44 hepatic
resections, 12 selective portal branch ligations, 46
radiological examinations of portal veins, and three
autopsies. We report here the data recorded during
the course of these procedures.
The aim of this article is to describe the surgical
anatomy of the liver and portal triad and to
document the vascular and segmental anatomy of
the cynomolgus monkey liver. We discuss its similarity to and difference from the liver of other
animals used for experimental purposes, and the
human liver.
METHODS
The monkeys were maintained in the primate
unit of the ‘‘Institut National de la Recherche
Agronomique (INRA)’’ at Jouy-en-Josas, France.
They were housed individually, in standard primate
cages with free access to food and water. All were in
good general health and all tested seronegative for
the simian herpes virus. (The simian herpes B virus
can be transmitted to humans through bite or
scratch or spit. There is no treatment for the
infection and nearly 80% of humans who contract
the disease die as a result). No animal was sacrificed
for the purposes of these experiments or only to
describe its anatomy. All research reported in this
article adhered to the American Society of Primatologist (ASP) Principles for the Ethical Treatment of
Nonhuman Primates. All experiments were performed according to the guidelines of the French
Ministry of Agriculture that regulates animal
research in France. The protocol was approved by
the Comité Régional d’Ethique en matière d’Expérimentation Animale (Creea ‘‘Ile-de-France-Sud’’).
Altogether, between 1995 and 2000, data were
recorded from 59 female cynomolgus monkeys, aged
774 years (range 3–15 years), and weighing
3.670.7 kg (range 3.1–5.5 kg). Animals were sedated
with an intramuscular injection of 10 mg/kg
ketamine and 10 mg/kg atropine to allow their
transport from the facility to the operating room.
Anesthesia was induced by inhalation of an increasing concentration of halothane (0.2%) and intravenous sufental (0.3 mg/kg) (Sufentas, Janssen-Cilag,
SA, Issy-les-Moulineaux, France). The trachea was
intubated and the lungs were manually ventilated
with 100% O2 throughout the surgical period. The
end-tidal CO2 was monitored continuously so that
hypoventilation or hyperventilation could be
avoided. Anesthesia was maintained with halothane
(0.7–1.5%). Subcutaneous sufentanil (0.2 mg/kg) was
administered at the end of surgery for postoperative
analgesia. When the animals had sufficient spontaneous ventilation, the trachea was extubated.
Forty-four animals underwent anatomical resections (34 of the left lateral lobe and 10 of the right
lateral lobe) in a first phase. During these 44
resections, liver lobulation and the extra hepatic
aspect of the portal vein and artery and their division
were gleaned from careful observation and notes.
Information about vascularization, i.e., portal vein,
hepatic artery, and hepatic vein, of the two resected
lobes (34 left and 10 right) was also recorded.
Resected livers (34 left lateral lobes and 10 right
lateral lobes resected) were weighed.
Then, in a second phase, ligations of both the left
portal vein and the right anterior portal vein were
performed in 12 additional animals to induce liver
parenchyma regeneration of the nonligated lobe
(corresponding to the region supplied by the right
posterior portal vein). Portal vein division dissections were performed at the hilum of the liver for
selective ligation using an anterior approach; therefore, the origins of the left and right portal vein were
documented.
In 46 of these 56 animals, a catheter was inserted
in the inferior mesenteric vein and connected to a
subcutaneous chamber placed in the lower left
quadrant of the abdominal wall. Permanent access
to the portal vein was therefore possible via the port
under light general anesthesia and the portal system
could be opacified by injection of 3 ml of contrast
medium (Hexabrixs 320 mg/ml, Guerbet, Zurich,
Switzerland) into the inferior mesenteric vein.
Thirty-four portographies following left lateral lobe
resection allowed the analysis of the portal division,
the portion that was resected being at the periphery of
the liver. Twelve additional portographies following
selective left portal vein and right anterior portal vein
ligations assessed the appropriateness of the anatomical description of the origins of the ligated right
anterior portal vein and left portal vein, and of the
nonligated right posterior portal vein.
Three additional animals, which died in the
primate unit from causes unassociated with this
work, were used for anatomical studies. They were
mostly used for photography: indeed good quality
pictures were difficult to obtain during surgery
because of the very small size of the animals and
the small abdominal incisions. However, after
autopsies, the whole liver with the entire inferior
vena cava (IVC) could be resected. Resected livers
were fixed in formaldehyde solution (37%) for 1
month. Whole livers and their ventral, caudal,
dorsal, and cranial surfaces were photographed first.
Livers were then carefully dissected. The portal vein
and the hepatic artery and their branches, the bile
ducts, and the gall bladder were isolated. About fifty
photographs were taken of the three whole livers
totally resected, documenting each of their surfaces,
with the livers being moved to provide different
Am. J. Primatol.
402 / Vons et al.
views; each step of dissection of the portal triad was
also photographed. We did not dissect the median
hepatic vein during surgery to determine whether it
was joined by any left or right hepatic veins before
entering the IVC and therefore cannot describe it.
A professional draughtsman then drew the
illustrations presented here from these detailed
photographs.
The records and descriptions performed during
all these procedures were combined for analysis to
describe: (1) the external aspect of the liver and its
lobation; and (2) portal vein, portal division, and
branches (44 measurements were performed during
hepatic resections and 12 during selective vein
ligations) and to a lesser extent hepatic arteries
and bile ducts, and branches of right and left hepatic
veins. Small arteries, bile ducts, and main hepatic
veins were not dissected during surgery to avoid
increased risk to the animals. Small arteries and bile
ducts were too small after their main convergence or
divergence to be clearly identified during autopsy.
We paid particular attention to portal division and
segmentation of the cynomolgus monkey liver
because arteries and bile duct are known to follow
them, and because major differences between
humans and other mammals—especially pigs and
dogs—concern portal division [Court et al., 2003;
Left
Lateral
Lobe
Right
Lateral
Lobe
Kamimura et al., 1997; Peng et al., 2005; Van Minh,
1996; Veeragandham et al., 1993].
Our examination of portal vascularization in the
cynomolgus monkey included an assessment of its
segmental distribution. We were able to develop a
nomenclature consistent with that of the human
liver.
RESULTS
Lobes and Fissures
In all 59 monkeys, the liver was divided into
three main lobes separated by two deep interlobular
fissures: the median lobe and the left and right
lateral lobes. A fourth less well-delimited lobe, called
the caudate lobe, was dorsal.
The median lobe
The ventral surface of the liver is almost
exclusively the median lobe (Fig. 1a). This lobe is
the largest of the three main lobes and it partially
covers the others (Fig. 1a). On its anterior border,
there is a groove visible on the ventral side of the
liver corresponding to the insertion of the falciform
ligament, the free border of which contains the
round ligament, i.e., the obliterated umbilical vein
(Fig. 1a). The falciform ligament attaches the median
Gall bladder
Round ligament
Right
Median
Lobe
Median Lobe
Left
Median
Lobe
Left Lateral
Lobe
Right
Lateral
Lobe
Caudate Lobe
Round ligament
a
The two protuberances of the caudate lobe
b
Caudate
Lobe
Right
Lateral
Lobe
Caudate
Lobe
Left
Lateral
Lobe
Left
Lateral
Lobe
The two protuberances of the caudate lobe
Median Lobe
Inferior Vena Cava with the endings of the right, median and left
hepatic veins
c
d
Fig. 1. External aspect of the cynomolgus monkey liver with its four lobes. (a) Ventral surface of the cynomolgus monkey liver; (b)
caudal surface of the cynomolgus monkey liver; (c) cranial surface of the cynomolgus monkey liver; (d) dorsal surface of the cynomolgus
monkey liver.
Am. J. Primatol.
Anatomy of the Cynomolgus Monkey Liver / 403
lobe to the diaphragm and to the anterior wall of the
abdomen. On the caudal surface of the liver, the
median lobe is subdivided by a deep umbilical fissure,
which extends almost up to the hilum, giving
the appearance of two separated median lobes, which
we called the left and right median lobes (Fig. 1b).
The gall bladder also lies on the caudal surface of the
liver, to the right of the deep fissure described above,
and separates the right median lobe into two smaller
parts, on its right and left sides (Fig. 1b).
Left lateral lobe
The left lateral lobe is clearly visible on the
caudal surface of the liver (Fig. 1b). It can only be
seen with difficulty on the ventral surface of the liver
because it is almost entirely hidden by the median
lobe (Fig. 1a). The left lateral lobe is thin but large,
and trapezoidal in shape, with a small protuberance
on its medio-caudal area, which partially covers the
left side of the portal triad and a part of the gall
bladder (Fig. 1b). It weighs 40–60 g (n 5 34). When
the deep fissure between the median and the left
lateral lobes is opened and its small internal
protuberance resected, the left lateral lobe can be
seen to be connected to the rest of the liver by only a
very thin portion of parenchyma, which contains its
vessels: its hepatic vein is at the superior part of the
band of hepatic parenchyma between the lobe and
the rest of the liver, just inferior to its portal vein and
at some distance below its artery. The bile duct
coming from left lateral lobe was too small to be
clearly identified (Fig. 2a).
The left lateral lobe is attached to the diaphragm
by a thin ligament, the left triangular ligament.
Right lateral lobe
The right lateral lobe is clearly visible on the
caudal surface of the liver (Fig. 1b). It is thin and
pyramidal. It weighs 50–60 g (n 5 10). It is attached
to the diaphragm by a thin ligament, the right
Left Median
Lobe
Right
Median
Lobe
Confluence of
hepatic ducts
Cystic
duct
Caudate lobe
The fourth lobe of the liver, called the caudate
lobe, can be seen only on the dorsal (Fig. 1d) and
cranial (Fig. 1c) surfaces of the liver and, to a lesser
extent, on its caudal surface (Fig. 1b). The caudate
lobe, with its rectangular shape, occupies all the
dorsal side of the liver and completely encircles the
IVC (Fig. 1b and c). On the caudal surface, the
inferior portion of the caudate lobe can be seen
dorsal to the portal pedicle and ventral to IVC, where
it forms two lateral horizontal protuberances, visible
on either side of the portal pedicle (Fig. 1b). It has a
large connection with the right lateral lobe. However, it is not connected to the left lateral lobe.
Vessels and Bile Ducts
In all 59 monkeys, the portal triad and extra
hepatic portal divisions could be observed during 44
hepatic resections, 12 portal vein division dissections
and ligations, 34 portographies and, to a lesser
extent, on photographs taken during three autopsies
(the basis of the illustrations).
Portal vein and divisions
The extra-hepatic portion of the portal vein was
10–15 mm long and 2–3 mm in diameter (56 measurements) and was devoid of branches. The portal
Left
Lateral
Lobe
hepatic vein,
portal vein,
artery
Gallbladder
Right
Lateral
Lobe
triangular ligament. When the median and right
lateral lobes are spread along the right fissure, which
is not as deep as the left fissure, the right lateral lobe
can be seen to be connected to the rest of the liver
only by a thin portion of parenchyma, which contains
its hepatic vein in the superior part, and inferior the
portal and arterial branches and bile duct (Fig. 2b).
The bridge of parenchyma connecting the right
lateral lobe to the rest of the liver is thicker than
that connecting the left lateral lobe and a portion lies
behind the IVC (Fig. 1d).
Hepatic
artery and
division
Right Median
Lobe
Gallbladder
Right
Lateral
Lobe
hepatic vein
Anterior right portal vein
Left Lateral
Lobe
Left portal vein
Portal vein
a
Left
Median
Lobe
Posterior right
portal vein
Small trunk of
right portal vein
b
Fig. 2. Caudal surface of the cynomolgus monkey liver with exposure of portal triad, the left and right lateral lobes, and their portal
pedicles. (a) Exposure of the elements of the portal triad (caudal surface, the left deep fissure has been opened and the internal small
protuberance of the left lateral liver resected); (b) exposure of the portal vein and its branches. Exposure of the right lateral lobe (caudal
surface, the right deep fissure has been opened).
Am. J. Primatol.
404 / Vons et al.
vein divides at the hepatic hilum into right and left
veins supplying the right and left parts of the liver.
However, the anatomy of division of the portal
vein differs between individual female animals. In 20
portographies (60%), the right portal vein had a very
short trunk (2–3 mm) before it divided into anterior
and posterior branches of 1–2 mm in diameter
(Fig. 3a). This is the case in the illustration shown
in Figure 2b: after dissection of the liver of one of
three autopsied animals, opening the deep left
fissure between the left and median lobes and
retracting upwards both the hepatic artery and the
bile duct, revealed, in this monkey, a portal bifurcation and the right portal vein with a short common
trunk. In 14 portographies (40%), however, there
was a trifurcation of the portal vein (Fig. 3b): the
trunk of the right branch was absent with immediate
division into anterior and posterior branches. Both
these patterns, bifurcation (60%) and trifurcation
(40%), were also observed during 12 portal vein
division dissections before selective ligation of
branches of the right portal vein (seven bifurcations
and five trifurcations of portal vein).
After the right portal vein divides, just upstream
from its point of entry into the liver, the posterior
branch curves posterior-laterally, lying in a horizontal plane, and separates into ascending and descending branches, heading toward the right lateral lobe
(Figs. 2b and 3). The anterior branch curves forward,
lies in a vertical plane, and divides to supply the part
of the median lobe located on the right side of the gall
bladder (ramus ascendens) [Couinaud, 1957]
(Figs. 2b and 3). Observation and measurements
performed during 34 anatomical resections of the
left hepatic lobe revealed that the extra-hepatic
portion of the left portal vein was much longer than
that of the right portal vein and its course could
be subdivided into two parts: a transversal part
5–7.5 mm long and a 4–5 mm-long section that
curves anteriorly and to the left as an arch toward
the base of the umbilical fissure. Just before turning
and entering the umbilical fissure, there was a
1–2 mm-diameter branch from the left portal vein
to the left lateral lobe (34 measurements). The part
of the left portal vein that curves anteriorly and to
the left of the base of the umbilical fissure was extrahepatic; close to the umbilical ligament, it divides
into two branches, to the right and left. All the left
branches are outside the hepatic parenchyma and
are covered by peritoneum.
Hepatic arteries
Hepatic arteries could be observed in their
extra-hepatic portion in all 44 resections performed
in female cynomolgus monkeys; however, observations during the 12 additional anterior portal vein
division dissections and the three postmortem total
Fig. 3. Opacification of portal vein and branches and illustrations. Note that the small portal branch to the left lateral lobe has been
ligated and is not opacified. (a) Bifurcation of the portal vein (60% of cases); (b) trifurcation of the portal vein (40% of cases).
Am. J. Primatol.
Anatomy of the Cynomolgus Monkey Liver / 405
liver dissections were more comprehensive. The
common hepatic artery lies within the hepatic
pedicle anterior to and to the left of the portal trunk.
The division of the hepatic artery is at the same level
as that of the portal vein and of bile duct confluence
(Fig. 2a). At the portal division, the common hepatic
artery divides into two branches (Fig. 2a). The
hepatic artery and its branches follow portal
branches all along their length.
The IVC emerges from the liver for 5–7 mm before
passing through the diaphragm and entering
the heart (44 measurements during section of the
coronal ligament before resection of the left or the
right hepatic lobes). The infra hepatic IVC was
studied in livers retrieved during the three autopsies.
It enters the liver between the portal pedicle and the
caudate lobe and rapidly it becomes entirely embedded in the hepatic parenchyma.
Gall bladder and bile ducts
The gall bladder, cystic duct, and main bile ducts
could be observed in their extra-hepatic portion in all
female cynomolgus monkeys during the 44 hepatic
resections. Right and left bile ducts were more
confidently observed during the 12 anterior portal
vein division dissections and the three postmortem
total liver dissections. The gallbladder is long and
fusiform and lies within a fossa on the inferior
surface of the large median lobe. It is deeply
embedded in the liver (Fig. 1b), and the fundus can
only sometimes be seen protruding on the anterior
side of the liver. The cystic duct is long, joining the
common bile duct close to the first portion of the
duodenum. The common bile duct lies anterior to
and to the right side of the main portal vein. It is the
lateral structure furthest to the right within
the peritoneal sheath of the portal triad, 2–3 mm to
the right of the common hepatic artery. The
confluence of the right and left bile ducts is adjacent
to the hilum of the liver (Fig. 2a). Right and left bile
ducts lie anterior to the right and left portal veins.
Posterior and anterior branches of the right bile duct
lie on the anterior side of the posterior and anterior
branches of the right portal vein. The anterior and
posterior right bile ducts always join the main bile
duct in close proximity to each other. Smaller bile
ducts could not be clearly identified.
Functional Anatomy
Hepatic veins
There are three main hepatic veins (right, left,
and median). Resections of the left lateral hepatic
lobe (34 cases) and of the right lateral hepatic lobe
(10 cases as well as), the three autopsies demonstrated that the left hepatic vein is formed by two
branches that drain the left lateral and left median
lobes, respectively. The hepatic vein draining the left
lateral lobe had a 3–4 mm-long extra-hepatic segment (Fig. 2a; 34 resections). The right hepatic vein
is also formed by two branches that drain the right
lateral and right median lobes, respectively. The
hepatic vein draining the right lateral lobe had a very
short extra-hepatic segment (Fig. 2b).
Inferior vena cava
Details concerning the supra hepatic IVC could
be obtained from careful observation and notes made
during 44 hepatic resections and three autopsies.
The description of the functional anatomy of the
human liver, by Couinaud, divided the liver into
hepatic segments on the basis of portal pedicle
distribution and hepatic vein location [Couinaud,
1957]. This type of distribution is also found in
animals with a lobed liver and therefore the same
classification can be applied [Couinaud, 1957; Kogure
et al., 1999]. The cynomolgus monkey liver can be
divided into eight independent segments, each with
its own vascular inflow, outflow, and biliary drainage
(Fig. 4a). The caudate lobe is segment I and is
posterior (not shown). The left lateral lobe is
segment II and is a left posterior segment (Fig. 4a).
The median lobe is divided by the main portal
scissura (which runs posterior from the middle of the
gall bladder fossa to the right side of the IVC) into a
left anterior sector, containing segment III laterally
(left median lobe) and segment IV medially (left side
of the right median lobe) (Fig. 4a), and a right
anterior sector, containing segments V and VIII
(right side of the right median lobe) on its inferior
and superior faces, respectively (Fig. 4a). The right
lateral lobe corresponds to a right posterior sector,
containing segments VI and VII on its inferior and
superior faces, respectively (Fig. 4a). In the cynomolgus monkey there are thus four posterior
segments (I, II, VII, and VI) and four anterior
segments (III, IV, V, VIII).
Comparisons of the lobation and portal distribution of the cynomolgus monkey liver with the livers
of other animals is shown in Figure 4 in which the
right lateral and left lateral lobes are shown with
darker shading in all species (Fig. 4b: rat; Fig. 4c: pig;
and Fig. 4d: human).
DISCUSSION
As far as we are aware, this article presents the
first description of the surgical anatomy of the
cynomolgus monkey liver and, indeed, of any nonhuman primate liver. These findings were obtained
during research for other aims, and no animal was
sacrificed or hurt for this study. We show that the
cynomolgus monkey liver is lobated, like the liver of
the other large mammals most frequently used for
research purposes, namely pigs and dogs. But more
importantly, this study documents how the cynomolgus monkey liver differs from that in other
Am. J. Primatol.
406 / Vons et al.
a. Cynomolgus monkey liver
b. Rat liver
Anterior right portal vein
Anterior right portal vein
Posterior right portal vein
Posterior right portal vein
c. Pig liver
Anterior right portal vein
Posterior right portal vein
d. Human liver
Anterior right portal vein
Posterior right portal vein
Fig. 4. Comparison of lobulation and portal distribution in (a) cynomolgus monkey liver; (b) rat liver; (c) pig liver; (d) human liver. The
right lateral and left lateral lobes are shown with darker shading in all species to demonstrate their divergence.
nonprimate mammals: among all large mammals
whose livers have been described, the cynomolgus
monkey liver is the most similar to that in humans.
Several articles have described the anatomy of
the pig’s liver [Camprodon et al., 1977; Kamimura
et al., 1997; Peng et al., 2005; Van Minh, 1996] and a
few the anatomy of the dog’s liver [Sleight &
Thomford, 1970; Veeragandham et al., 1993]. There
are only three reports of surgical liver resection in
nonhuman primates, one using an anatomic resection technique [Houssin et al., 1988] and the others a
nonanatomic finger fracture technique [Talcott &
Dysko, 1991] or an automatic stapling device [Nolan
& Conti, 1980]. For our research purposes, we mostly
performed resections of a small anatomic area, the
left lateral lobe, this being straightforward, as in pigs
and dogs. To a lesser extent, the right lateral lobe
was easily and safely resected because of the band of
parenchyma situated between this lobe and the rest
of the liver and also because the right lateral lobe is
larger than the left lateral lobe. During these
resections we could carefully observe liver lobation
Am. J. Primatol.
and triad structures of this specimen. Additionally,
during portal vein division dissections and branch
ligations, and portographies, we were able to
describe portal division in a large number of
individual animals.
The main anatomical difference reported to date
between human and described animal livers includes
the division of the main portal vein [Couinaud,
1957]. This difference also distinguishes the cynomolgus monkey liver from the livers of other large
mammals including those of the pig and the dog.
Therefore, the cynomolgus monkey liver appears to
be most similar to the human liver. There are,
nevertheless, differences. In particular, the caudate
lobe encircles the IVC in all cynomolgus monkey
livers, whereas this is observed in only 5% of humans
[Hawkins et al., 2005].
Couinaud [Couinaud, 1957; Couinaud & Rene,
1981] divided the human liver into eight segments.
Dissections of lobes of small and large mammals
demonstrated the same internal segmentation regardless of their external appearance [Couinaud, 1957].
Anatomy of the Cynomolgus Monkey Liver / 407
Our study confirms that this segmental anatomy can
also be applied to the lobated liver of the cynomolgus
monkey. One consequence of the division of the liver
into self-contained units is that each segment can be
resected without damaging the remaining segments.
The cynomolgus monkey liver differs from pig and rat
livers as concerns lobation, and more importantly
portal division (Fig. 4a): the lateral lobe in the
cynomolgus monkey is more posterior than those in
other mammals, whether large or small. In addition,
the portal vein division in the cynomolgus monkey
differs markedly from that in other small and large
mammals. The emergence of the sectoral portal
branch supplying the right anterior sector (segments
V and VIII) is different. In the rat and the pig, this
branch emerges from the portal vein, distant from the
emergence of the sectoral branch (Ramus cysticus)
supplying the right posterior sector (segments VI and
VII) [Camprodon et al., 1977; Couinaud, 1957; Court
et al., 2003; Kamimura et al., 1997; Peng et al., 2005;
Robert, 1997] (Fig. 4b and c). The right anterior portal
vein therefore drains into the left portal vein. In
cynomolgus monkey and human, the branch supplying the right anterior sector (segments V and VIII) is
either one of the two branches of the right portal vein
(ramus ascendens) or one of the branches of trifurcation of the portal vein (Fig. 4a and d). In the
cynomolgus monkey, this trifurcation is found in
40% of cases. In human, such trifurcation is only
found in 10–15% of individuals [Deshpande et al.,
2002].
The cynomolgus monkey liver, like those of
other monkeys, is presumably closer phylogenetically to the human liver than are those of other
animals, in view of the evolutionary divergence
between small mammals (including rodents), large
mammals (pigs and dogs), and primates (humans
and monkeys). On the basis of the theory that the
development of the liver during gestation is similar
to its evolution from small to large mammals
(‘‘ontogeny recapitulates phylogeny’’), the similarities between mammalian livers, including that of
humans, could be used to elucidate the anatomical
variations in the human liver, such as the portal
branches [Deshpande et al., 2002] and left hepatic
vein [Reichert et al., 2000]. Considering the portal
branches, Deshpande noted a variant of the anatomy
of portal division, a trifurcation, in 15% of humans
[Deshpande et al., 2002], as in 40% of cynomolgus
monkeys: the right anterior portal vein supplying the
right anterior segments V and VIII divides from the
left portal vein a short distance from its origin
[Deshpande et al., 2002]. This is similar to the dog
[Sleight & Thomford, 1970] and pig [Camprodon
et al., 1977; Couinaud, 1957; Court et al., 2003;
Kamimura et al., 1997; Peng et al., 2005; Robert,
1997]. Considering the left hepatic vein, Reichert
described three patterns of left hepatic venous
drainage in humans [Reichert et al., 2000]: the most
common variant, observed in 73% of cases, is the
union of segments II and III veins to form a principal
left hepatic vein at the umbilical fissure; the second
most commonly observed pattern is separate large
veins (14%), similar to that found in the cynomolgus
monkey liver in our study.
The cynomolgus monkey liver has the same
right and left separation as in humans. Because of
the presence of a right and left portal veins, a large
anatomical resection (right and left hepatectomy)
can be performed using the virtual main portal
fissure [Houssin et al., 1988]. This type of large
resection cannot be achieved easily in pigs or dogs,
for example, in which a right hepatectomy would be
more difficult and lead to damage of the vascularization of the left and median lobes and subsequently to
the death of the animal [Couinaud, 1957].
Accurate description of cynomolgus monkey
liver, its lobation and the location, and distribution
of its vessels, provide a valuable background for
future liver surgery in this nonhuman primate and
strengthens its potential as a model for development
of surgical techniques applicable to humans.
ACKNOWLEDGMENTS
We thank Lien Nguyen and Elisabeth Heseltine
for help with the English language. We also thank
the editor and reviewers of the Journal of Primatology, for their very helpful comments. The authors
are grateful for financial support from AFM (Association Franc- aise contre les Myopathies) and from
Inserm. All research reported in this study adhered
to the American Society of Primatologist (ASP)
Principles for the Ethical Treatment of Nonhuman
Primates. All experiments were performed according
to the guidelines of the French Ministry of Agriculture that regulates animal research in France. The
protocol was approved by the Comité Régional
d’Ethique en matière d’Expérimentation Animale
(Creea Ile-de-France-Sud).
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