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Chapter 1
1. Initiation
Increased portal flow
Lipopolysaccharides
Soluble factors
Hepatic
sinusoid
Serotonin
Platelets
Sinusoidal
endothelial
cell
Figure1.6 • Schematic of some of the factors known to regulate liver regeneration.
Kupffer cell
TNF alpha
Interleukin-6
Hepatocyte
Stellate cell
Epidermal
growth factor
Hepatocyte
growth factor
Extracellular
matrix
2. Hepatocyte
priming
TGF-b
3. Hepatocyte
proliferation
Insulin
adrenaline
–
+
of circulating extrahepatic cells in liver regeneration
has received interest recently and the potential bone
marrow origin of hepatocytes has been suggested.
However, if this phenomenon occurs at all, it is extremely rare. The bone marrow does, however, supply
macrophages and myofibroblasts that are involved in
the liver's scarring response to injury. The relationship
between bone marrow-derived cells and the response
to injury is complex, with different macrophage
subtypes shown to either promote fibrosis or repair.
However, administration of bone marrow-derived
macrophages to the fibrotic liver via the portal vein
has been shown to reduce fibrosis and improve markers of regeneration in preclinical models.29 The use of
bone marrow populations to stimulate liver regeneration in both animal models and clinical studies is
likely to be an area of future development (see later).
Consequences of surgery
Unfortunately, at present it is unclear what the key
mechanisms of liver failure are, and why the liver usually regenerates but sometimes progresses into liver
failure. It is believed that ischaemia/reperfusion (I/R)
injury plays an important role in the sequence of events
leading to liver failure. Hepatic resections are major
surgical procedures, often leading to significant blood
loss. In order to reduce blood loss, central venous pressure is reduced during liver surgery and hepatobiliary
surgeons frequently occlude hepatic blood inflow
temporarily (Pringle manoeuvre). Obviously, all these
factors may contribute to I/R injury in the liver. A key
component of I/R injury is the generation of oxygen
free radicals. The latter can induce ischaemic necrosis
and caspase-dependent apoptosis, and may contribute to failure of vital metabolic synthetic pathways.
However, it remains to be investigated which one of
these plays a key role during liver failure. In this context, it has been proposed that the balance between
hepatocyte regeneration and apoptosis can be tipped
towards either side by hepatic defence mechanisms
against oxygen free radical damage. Also, oxygen free
radicals play a role in determining whether apoptosis
or ischaemic necrosis occurs in the liver. Apparently,
the equilibrium between oxygen free radicals and their
scavengers plays a pivotal role in determining whether
regeneration or decay occurs. Glutathione (GSH) is the
principal oxygen free radical scavenger in the liver and
the principal defence mechanism against I/R damage.
Hepatic GSH levels decrease following I/R damage,
inflammation and nutritional deprivation. It seems
conceivable that a reduction in liver volume following
surgery contributes to insufficient hepatic free radical
scavenging capacity as a consequence of reduced GSH
synthesis. I/R injury may aggravate this situation.
Small-for-size syndrome
The original descriptions of small-for-size syndrome described a condition arising in split liver
10
Liver function and failure
transplantation characterised by the development
of ascites, portal hypertension and liver dysfunction in an otherwise healthy transplanted portion
of liver. The underlying cause for this syndrome is
believed to relate to blood flow and the failure of
a small liver volume to cope with often very high
blood flows of patients with previous chronic liver
disease undergoing transplantation. The validity of
this hypothesis was supported by the observation
that partial diversion of portal blood flow into the
graft using a portocaval shunt could limit or prevent the development of small-for-size syndrome.
Subsequently, other manoeuvres have also been
effected, such as ligation or embolisation of the
splenic artery, which works in the same way by reducing portal vein flow.
In patients undergoing even very major liver
resection it is rare to develop small-for-size syndrome. Some patients do, however, develop ascites, jaundice and chronic liver dysfunction, and it
is more likely that this syndrome is more dependent on a failure to regenerate than on excessive
blood flow.
Hepatic steatosis
Fat infiltration of the liver is an increasing problem with increased prevalence of obesity and the
metabolic syndrome (obesity and type 2 diabetes). Macroscopically the liver may appear enlarged, pale or yellow coloured with rounded edges.
Microscopically the liver can have microsteatosis
(small fat droplets within every hepatocyte) or macrosteatosis (regional infiltration of hepatocytes with
large fat droplets) (see Fig. 1.7).
Figure1.7 • Macroscopic and microscopic images of
steatotic liver.
Assessment of steatosis
Assessment of hepatic steatosis is notoriously difficult. Experienced surgeons can estimate liver fat
by judging the size, rounded or sharp edges of the
liver and its appearance. Even using colour as an
estimate is prone to error, as can be seen in Fig. 1.8.
The gold standard for hepatic fat assessment is histology. Trucut or wedge biopsies can be assessed by a
pathologist and a reliable estimate of the percentage
fat content produced. In addition, useful information
including the distribution – macrosteatosis or microsteatosis – and the presence of fibrosis or inflammation can be provided. New MRI techniques are,
however, challenging the accuracy of pathological
assessment of steatosis and offer the potential advantage of being non-invasive.
30
Chemotherapy-induced liver changes
Increased usage of chemotherapy in the neoadjuvant
context has revealed changes in the liver associated
with chemotherapy, particularly oxaliplatin and irinotecan. These range from a soft, fragile pale liver to steatosis, steatohepatitis and sinusoidal dilatation. Surgery
should be deferred until 6 weeks after chemotherapy
and studies, although conflicting, suggest that tolerance
of major liver resection may be reduced and complications more frequent in individuals who have received
chemotherapy. A study by Mehta et al. showed that
oxaliplatin-based chemotherapy was associated with
increased blood loss and prolonged hospital stay.
31
Portal vein embolisation
Morbidity and mortality after hepatectomy have constituted a limitation on the number of patients eligible
for resection, and currently only 8% of patients with
colorectal hepatic metastases are candidates for curative liver resection. Liver function is correlated with
liver volume, and consequently hepatic insufficiency in
this situation may arise because not enough functional
liver volume is left after surgical removal of part of
the liver. Interestingly, following removal of part of the
liver, the residual liver usually regenerates to the point
where the preoperative liver weight–body weight ratio
is regained. This notion has led to the belief that if it
were possible to increase preoperatively the volume of
<5%% fat 6–15% 16–30% 31–45% 46–60% 61–75% >76%
Figure1.8 • Physical appearance of livers with varying fat content confirmed by histology to demonstrate the poor
correlation between colour and objective measurement of fat content.
11
Chapter 1
Predicted residual liver volume (%)
60
the future residual liver, it would be possible to perform more extensive liver resections and hence cure
more patients. It has long been recognised that interruption of one part of the liver portal blood flow
usually leads to hypertrophy of normally vascularised
liver. This has been observed in patients with Klatskin
tumours, which have a tendency to invade the portal vein, causing ipsilateral atrophy and contralateral
hypertrophy. This concept has subsequently been harnessed by manoeuvres such as embolising the right
portal vein prior to surgical resection. This leads to
hypertrophy of the left liver lobe prior to surgery and
facilitates the subsequent safe extensive resection of
the right liver (extended right hepatectomy) 6 weeks
later (Fig. 1.9). This phenomenon has been harnessed
to maximise the residual functional liver volume of patients who are predicted to have a small remnant liver
volume. This approach is fully based on the concept
that, in the normal liver, volume is correlated to func-
tion and hence liver failure occurs when residual liver
volume is too small. A completely different and novel
approach would be to improve liver function per
volume unit of liver. Recent evidence from studies
using mebrofenin suggests that functional improve-
ment of the future liver remnant following portal vein
embolisation (PVE) may precede changes in liver vol-
ume.32 This important observation suggests that sur-
gery earlier after PVE may be possible. Limitations to
PVE-induced hypertrophy include pre-existing hepatic
fibrosis or cirrhosis and technical or anatomical inabil-
ity to completely obstruct a major portal vein branch.
Technique
The most common technique of PVE is to punc-
ture a branch of the vein using a percutaneous ap-
proach. A venogram is obtained to demonstrate
all of the relevant branches and then the branch
to be embolised is cannulated and coils and em-
bolic material delivered to obstruct portal flow.
A check angiogram can be performed to demon-
strate success of the technique. Usually either a
left or right main branch is occluded. To obtain
hypertrophy of segments 2 and 3 in large right-
sided tumours, it is not sufficient to embolise just
the right portal vein and it is recommended that
the branches supplying segment 4 should also be
embolised. Patients usually tolerate PVE remark-
ably well, presumably because of the dual blood
supply of the liver, and complications are uncom-
mon. Significant hypertrophy can be achieved, as
can be seen in Fig. 1.10.
a
b
Figure1.9 • Portal venograms showing the main left
and right branches prior to embolisation (a), and after
embolisation of the right portal vein (b).
12
50
40
30
20
10
0
Pre-PVE Post-PVE
Figure1.10 • Calculated residual liver volumes before
and after portal vein embolisation (PVE) in patients
scheduled to undergo major liver resection.
Liver function and failure
Therapy for liver failure
N-Acetyl cysteine
Glutathione depletion is a major problem in patients with paracetamol (acetaminophen) toxicity.
N-Acetyl cysteine has been used for many years as
a treatment for early paracetamol poisoning. It is
thought to act by replenishing glutathione stores
and by providing alternative thiol groups to which
damaging reactive oxygen species can bind. The
realisation that reactive oxygen species can be
generated by conditions other than paracetamol
poisoning such as sepsis and ischaemia/reperfusion
has led to N-acetyl cysteine being used in a more
general way to support patients with early evidence
of liver dysfunction or failure.
Nutritional support in liver failure
The role of nutritional support in acute liver failure
is uncertain, largely because of a lack of evidence
in the world literature. Enteral nutrition is known
to preserve gut barrier function and thus might be
considered to be beneficial in the context of liver
failure. In addition, the provision of energy might
be considered beneficial in the context of glycogen
storage failure, and to fuel the regeneration of liver
tissue and recover function. The limited ability of
the failing liver to handle nitrogen and synthesise
urea (potentially exacerbating encephalopathy)
would argue against excessive provision of proteins
unless these were in a form where they did not contribute to the circulating ammonia load.
Artificial extracorporeal liver support
For the vast majority of patients who take toxic
doses of paractetamol, suffer alcohol-induced liver
injury or develop liver dysfunction following liver
resection, the regenerative capacity of the liver is
sufficient to prevent irretrievable liver failure and
death. However, when this regenerative capacity is
overwhelmed treatment strategies to temporarily or
permanently replace the failing liver are required.
The ability to provide short-term extracorporeal
liver support, either during the wait for transplantation or to facilitate liver regeneration and avoid
transplantation, is an attractive option. A range of
devices have been developed, either focusing on the
detoxification functions of liver (artificial liver support) or also incorporating bioreactors intended to
also perform synthetic liver functions ( bioartificial
liver support). Assessment of efficacy has been
hampered by the limited number of randomised
controlled trials and small sample size, but a recent
meta-analysis does suggest overall survival benefit
in acute liver failure.
33
Artificial liver support
Artificial systems include the MARS (Molecular
Adsorbent Recirculating System) device, Prometheus
and the BioLogic-DT (now called the Liver Dialysis
Device, currently being redesigned). The greatest
experience has been with the MARS device, which
deploys an albumin dialysis circuit to remove both
water- soluble and protein-bound toxins.34 Thus, a low
Fischer ratio can be corrected by recirculating albumin
dialysis.35 Because the system preferentially removes
AAAs, compared with BCAAs, the Fischer ratio significantly increases, predominantly by the removal of
AAAs in a small series of patients.
shown to be useful in fulminant hepatic failure, by attenuating the increase in intracranial pressure, which
plays a major role in this situation.32 There may also
be an effect on survival and improvement of degree
of hepatic encephalopathy in patients with acute or
chronic liver failure.
tested on artificial neuronal networks showing a normalisation of abnormal signals if the medium (plasma
derived from rats with liver failure) was pretreated
with MARS. The role of MARS in a more chronic situation of mild hepatic encephalopathy, when correction of an abnormal Fischer ratio would likely be more
important if this were a major pathogenetic factor, is
still largely unknown and deserves further study.40 It
has been suggested that the role of MARS and bioartificial liver support systems should be limited to
carefully designed clinical trials.41 It is currently uncertain how hepatic excretory assistance devices, such
as MARS, compare with bioartificial liver assistance
devices, which in addition to their excretory functions
aim to provide biosynthetic capacity.
37,39
Equally, the system has been
Bioartificial liver systems
Bioartificial systems incorporate a bioreactor containing either human hepatoblastoma cell lines (e.g.
the HepatAssist device) or porcine hepatocytes (e.g.
the ELAD – Extracorporeal Liver Assist Device),
through which the patient's blood is perfused. An
additional filter component may be included to aid
detoxification and improve bioreactor survival.
One of the major problems with these systems is
what type of cells to use, and a variety of different
approaches have been taken. Animal hepatocytes
perform many of the same functions as human
hepatocytes, although some of the proteins produced are obviously different. Human immortalised
cell lines are an attractive proposition and some of
the more differentiated cell lines can replicate many
of the normal hepatocyte functions. Regardless, the
35–38
MARS has been
37
13
Chapter 1
true functionality of these cells in the clinical setting
is uncertain. The design of bioartificial liver systems
is challenging and the large surface area of hepatocytes needed to be effective is difficult. Engineering
scaffolds of membranes or tubules has been the most
popular approach. In normal liver, hepatocytes are
polarised and have an epithelial surface. However, it
is still to be determined how to recreate this polarity
and its absolute importance has yet to be defined.
Hepatocytes proliferate and function better in association with non-parenchymal cells; however, the
creation of co-cultures in reactors produces its own
problems. Cells must maintain viability or be able to
be replenished to provide liver support over a prolonged period of time. In addition, very sick patients
require a short time period to set up the support system, and the reactor must be easy to use by critical
care nurses, safe from contamination and not overly
expensive. For all of these reasons, bioartificial liver
systems remain a tantalising prospect that has yet to
break through into routine clinical practice.
Liver transplantation
Irreversible acute or chronic liver failure is amenable
to treatment by liver transplantation. It is extremely
uncommon for patients who have undergone liver
resection to subsequently require or proceed to liver
transplantation. The most obvious reason for this is
that many patients who undergo liver resection do
so for metastatic or primary liver cancer and transplantation would be contraindicated because of the
risk of immunosuppression and aggressive recrudescence of the tumour. A number of patients with bile
duct injury have progressed to transplantation, usually in a chronic setting following the development
of biliary stricture, cholangitis and secondary biliary cirrhosis. Similarly, a number of patients who
have undergone a ‘cancer resection’ for what turned
out to be a benign biliary stricture, perhaps as part
of primary sclerosing cholangitis, fail to regenerate
their livers and may progress to transplantation.
Cell therapy for liver failure: general principles
A number of key principles have operated as key drivers for the development of cell therapies for clinical
treatment of liver failure. Firstly, it is recognised that
the injured liver usually provides a rich environment
stimulating tissue regeneration and the liver can
normally ‘heal’ itself. Secondly, in animal models
there is evidence that stem cells or non-parenchymal
cells can support regeneration of hepatocytes.
Thirdly, it is recognised that the difference between
liver failure and compensated liver function in terms
of cellular functional equivalents is probably very
small. Finally, it would be preferable to support the
liver by techniques that were within the body rather
than using extracorporeal devices. This desire has
stimulated research into therapeutic application of
cell or stem cell transplantation.
The dual goals of stem cell therapy in the context
of acute liver failure or injury are to promote rapid
recovery of hepatocyte function and to allow regeneration of liver tissue without excessive scarring.
Direct administration of hepatocytes or stem cellderived hepatocytes to the injured liver has been met
with little success in preclinical studies. However,
using bone marrow-derived cells to support endogenous processes may support the regenerating liver,
enabling effective regeneration.
42
Haemopoetic stem cell therapy for liver disease in humans
There are several reports in the scientific literature
of bone marrow (BM) stem cell therapy in patients
with advanced liver disease. It was first reported
that BM stem cells could increase the liver's ability
to regenerate in patients who were undergoing hepatic resection for various liver cancers sited in the
right lobe. Here the patients underwent embolisation of the right branch of the portal vein prior to
surgery to stimulate compensatory hypertrophy of
the left lobe. Autologous CD133-positive BM stem
cells were injected into the blood vessels that supply
the left liver lobe shortly after the surgery and accelerated regeneration of the non-embolised section of
the liver was seen compared with control patients.43
However, it must be stated that this was a small nonrandomised study. The second report used BM stem
cells in patients with liver cirrhosis.44 CD34-positive
stem cells were isolated from the patients' own blood
following granulocyte colony- stimulating factor
(GCSF)-induced haematopoietic stem cell mobilisation and were re-injected into the blood supply to the
liver – preliminary evidence appeared to show that
improvement in liver function in three out of five of
the patients occurred during this therapy. In the third
study, patients with liver cirrhosis had mononuclear
cells isolated from their own BM during general
anaesthesia.45 These cells were re-injected into the
patient's bloodstream and again the patient's liver
function appeared to improve. Although these studies
are very encouraging, they are preliminary, of small
numbers and non-randomised. Furthermore, in none
of these studies were the cells marked to enable identification either by radiological tracking or in biopsies
of the liver tissue. Therefore, a number of important
questions are unanswered. It is not certain that these
14
Liver function and failure
cells definitely settled in the liver over a period of time,
whether some of the cells engrafted other organs in
the body and by what mechanisms the cells were having their positive effects within the recipients' livers.
would be a major advantage. Preoperative functional enhancement might expand the group of
patients who would be amenable to surgery, while
postoperative intervention might be useful in liver
resection, transplantation and acute liver failure as
a means of rescuing a failing liver. The potential to
Future developments
use autologous stem cells derived from bone mar-
row to stimulate liver regeneration is enormous if
The ability to exert greater control in modulating
liver volume and function in the surgical patient
its positive effects are seen in larger randomised
studies.
Key points
• Conventional measures of liver function are poor and take no account of liver volume.
• Liver resection leaving a residual liver volume of <25% is associated with a high risk of liver
dysfunction and infection.
• In patients with chronic liver disease smaller resections can be dangerous.
• The combination of liver dysfunction and sepsis can be fatal.
• Preoperative portal vein embolisation and newer regenerative strategies may improve the safety of
liver surgery.
References
1. O'Grady JG, Alexander GJ, Hayllar KM, et al. Early
indicators of prognosis in fulminant hepatic failure.
Gastroenterology 1989;97:439–45.
2. Schindl MJ, Redhead DN, Fearon KC, et al. The
value of residual liver volume as a predictor of hepatic dysfunction and infection after major liver resection. Gut 2005;54:289–96.
The first paper providing strong evidence of an association between residual liver volume and clinical infection.
3. van Hoorn EC, van Middelaar-Voskuilen MC, van
Limpt CJ, et al. Preoperative supplementation with a
carbohydrate mixture decreases organ dysfunctionassociated risk factors. Clin Nutr 2005;24:114–23.
4. Kretzschmar M, Kruger A, Schirrmeister W. Hepatic
ischemia–reperfusion syndrome after partial liver resection (LR): hepatic venous oxygen saturation, enzyme
pattern, reduced and oxidized glutathione, procalcitonin
and interleukin-6. Exp Toxicol Pathol 2003;54:423–31.
5. Garcea G, Gescher A, Steward W, et al. Oxidative
stress in humans following the Pringle manoeuvre.
Hepatobil Pancreat Dis Int 2006;5:210–4.
6. Clavien PA, Yadav S, Sindram D, et al. Protective ef-
fects of ischemic preconditioning for liver resection
performed under inflow occlusion in humans. Ann
Surg 2000;232:155–62.
The first randomised clinical trial demonstrating benefit
in clinical markers from ischaemic preconditioning of the
liver in patients undergoing liver resection.
7. Patel A, van de Poll MC, Greve JW, et al. Early
stress protein gene expression in a human model
of ischemic preconditioning. Transplantation
2004;78(27):1479–87.
8. Pugh RN, Murray-Lyon IM, Dawson JL, et al.
Transection of the oesophagus for bleeding oesophageal varices. Br J Surg 1973;60:646–9.
9. Albrecht J, Jones EA. Hepatic encephalopathy:
molecular mechanisms underlying the clinical syndrome. J Neurol Sci 1999;170:138–46.
10. Shawcross D, Jalan R. The pathophysiologic basis of hepatic encephalopathy: central role for
ammonia and inflammation. Cell Mol Life Sci
2005;62:2295–304.
11. James JH, Ziparo V, Jeppsson B, Fischer JE.
Hyperammonaemia, plasma amino acid imbalance,
and blood–brain amino acid transport: a unified
theory of portal–systemic encephalopathy. Lancet
1979;2:772–5.
Explanation of the relationship between the urea cycle
and hepatic encephalopathy.
12. Fischer JE, Yoshimura N, Aguirre A, et al. Plasma amino
acids in patients with hepatic encephalopathy. Effects of
amino acid infusions. Am J Surg 1974;127:40–7.
13. Soeters PB, Fischer JE. Insulin, glucagon, aminoacid imbalance, and hepatic encephalopathy. Lancet
1976;2:880–2.
14. Fischer JE, Rosen HM, Ebeid AM, et al. The effect
of normalization of plasma amino acids on hepatic
encephalopathy in man. Surgery 1976;80:77–91.
15. Fischer JE, Baldessarini RJ. False neurotransmitters
and hepatic failure. Lancet 1971;2:75–80.
16. Wigmore SJ, Redhead DN, Yan XJ, et al. Virtual hepatic resection using three-dimensional reconstruction
15
Chapter 1
of helical computed tomography angioportograms.
Ann Surg 2001;233:221–6.
17. Dello SA, van Dam RM, Slangen JJ, et al. Liver volumetry plug and play: do it yourself with ImageJ.
World J Surg 2007;31:2215–21.
18. Zipprich A, Kuss O, Rogowski S, et al. Incorporating indocyanin green clearance into the Model
for End Stage Liver Disease (MELD-ICG) improves
prognostic accuracy in intermediate to advanced
cirrhosis. Gut 2010;59(7):963–8.
19. Bennink RJ, Dinant S, Erdogan D, et al. Preoperative
assessment of postoperative remnant liver function using
hepatobiliary scintigraphy. J Nucl Med 2004;45:965–71.
20. van de Poll MC, Wigmore SJ, Redhead DN, et al.
Effect of major liver resection on hepatic ureagenesis
in humans. Am J Physiol Gastrointest Liver Physiol
2007;293:G956–62.
Clinical experimental study demonstrating the relationship between liver volume and urea synthesis in patients
undergoing varying degrees of liver resection.
21. Vermeulen MA, Ligthart-Melis GC, Buijsman R,
et al. Accurate perioperative flow measurement of
the portal vein and hepatic and renal artery: a role for
preoperative MRI? Eur J Radiol 2012;81(9):2042–8.
22. van de Poll MC, Ligthart-Melis GC, Boelens PG,
et al. Intestinal and hepatic metabolism of glutamine
and citrulline in humans. J Physiol 2007;581:819–27.
23. van de Poll MC, Siroen MP, van Leeuwen PA, et al.
Interorgan amino acid exchange in humans: consequences for arginine and citrulline metabolism. Am J
Clin Nutr 2007;85:167–72.
24. Barbaro B, Manfredi R, Bombardieri G, et al.
Correlation of MRI liver volume and Doppler sonographic portal hemodynamics with histologic
findings in patients with chronic hepatitis C. J Clin
Ultrasound 2000;28:461–8.
25. Nanashima A, Shibasaki S, Sakamoto I, et al.
Clinical evaluation of magnetic resonance imaging
flowmetry of portal and hepatic veins in patients following hepatectomy. Liver Int 2006;26:587–94.
26. El-Desoky AE, Seifalian A, Cope M, et al. Changes
in tissue oxygenation of the porcine liver measured
by near-infrared spectroscopy. Liver Transpl Surg
1999;5:219–26.
27. Schindl MJ, Millar AM, Redhead DN, et al. The adaptive response of the reticuloendothelial system to major
liver resection in humans. Ann Surg 2006;243:507–14.
28. Boulter L, Govaere O, Bird TG, et al. Macrophagederived Wnt opposes Notch signaling to specify
hepatic progenitor cell fate in chronic liver disease.
Nat Med 2012;18(4):572–9.
29. Thomas JA, Pope C, Wojtacha D, et al. Macrophage
therapy for murine liver fibrosis recruits host effector cells improving fibrosis, regeneration, and function. Hepatology 2011;53(6):2003–15.
30. Raptis DA, Fischer MA, Nanz D, et al. MRI as
the new reference standard in quantifying liver
steatosis: the need for international guidelines. Gut
2012;61(9):1370–1.
31. Mehta NN, Ravikumar R, Coldham CA, et al.
Effect of preoperative chemotherapy on liver resection for colorectal liver metastases. Eur J Surg Oncol
2008;34:782–6.
32. de Graaf W, van Lienden KP, van den Esschert JW,
et al. Increase in future remnant liver function after preoperative portal vein embolization. Br J Surg
2011;98(6):825–34.
33. Stutchfield BM, Simpson K, Wigmore SJ. Systematic
review and meta-analysis of survival following extracorporeal liver support. Br J Surg 2011;98(5):623–31.
34. Tan HK. Molecular adsorbent recirculating system
(MARS). Ann Acad Med Singapore 2004;33:329–35.
35. Loock J, Mitzner SR, Peters E, et al. Amino acid
dysbalance in liver failure is favourably influenced
by recirculating albumin dialysis (MARS). Liver
2002;22(Suppl. 2):35–9.
36. Awad SS, Swaniker F, Magee J, et al. Results of a
phase I trial evaluating a liver support device utilizing albumin dialysis. Surgery 2001;130:354–62.
37. Mitzner S, Loock J, Peszynski P, et al. Improvement
in central nervous system functions during treatment
of liver failure with albumin dialysis MARS – a review of clinical, biochemical, and electrophysiological data. Metab Brain Dis 2002;17:463–75.
38. Steczko J, Bax KC, Ash SR. Effect of hemodiabsorption and sorbent-based pheresis on amino
acid levels in hepatic failure. Int J Artif Organs
2000;23:375–88.
39. Boyle M, Kurtovic J, Bihari D, et al. Equipment review: the molecular adsorbents recirculating system
(MARS). Crit Care 2004;8:280–6.
40. Hassanein TI, Tofteng F, Brown Jr RS, et al.
Randomized controlled study of extracorporeal
albumin dialysis for hepatic encephalopathy in advanced cirrhosis. Hepatology 2007;46:1853–62.
41. Ferenci P, Kramer L. MARS and the failing liver –
Any help from the outer space? Hepatology
2007;46:1682–4.
42. Stutchfield BM, Forbes SJ, Wigmore SJ.
Prospects for stem cell transplantation in the
treatment of hepatic disease. Liver Transpl
2010;16(7):827–36.
43. am Esch 2nd. JS, Knoefel WT, Klein M, et al. Portal
application of autologous CD133+ BM cells to the
liver: a novel concept to support hepatic regeneration. Stem Cells 2005;23:463–70.
44. Gordon MY, Levicar N, Pai M, et al. Characterisation
and clinical application of human CD34+ stem/
progenitor cell populations mobilised into the
blood by G-CSF. Stem Cells 2006;24:1822–30.
45. Terai S, Ishikawa T, Omori K, et al. Improved liver
function in liver cirrhosis patients after autologous
bone marrow cell infusion therapy. Stem Cells
2006;24:2292–8.
16
2
Hepatic, biliary and pancreatic anatomy
Steven M. Strasberg
The aim of this chapter is to provide the basic
anatomical foundation for performing liver, biliary and pancreatic surgery. Surgically unimportant
anatomical features are omitted, but anatomical
distortions due to pathological processes are included. A key point of hepato-pancreato-biliary
(HPB) surgical anatomy is that whilst there is a
prevailing pattern of anatomy, i.e. a pattern that is
most commonly found, variations from the prevailing pattern termed anomalies are frequent. Every
surgical operation in this area should be conducted
with this fact in mind.
Liver
Overview of hepatic anatomy and terminology
Modern hepatic anatomy is concerned mainly
with internal vascular and biliary structures rather
than surface markings. Ramifications of the hepatic artery and bile ducts are regular and virtually
identical. The portal vein on the left side of the liver
is a vessel with unusual morphology, consequent to
its need to perform different functions in the foetus and in the postnatal period. Consequently, the
Brisbane 2000 Terminology of Hepatic Anatomy
and Resections of the International HepatoPancreato-Biliary Association used in this chapter
is primarily based on hepatic artery and bile duct
ramifications.
1
Divisions of the liver based on the hepatic artery
The primary (first-order) division of the proper hepatic artery is into the right and left hepatic arteries (Fig. 2.1). These branches supply arterial inflow
to the right and left hemilivers or livers (Fig. 2.2).
The plane between the two distinct zones of vascular supply is called a watershed. The border or
watershed of the first-order division is called the
midplane of the liver. It intersects the gallbladder fossa and the fossa for the inferior vena cava
(IVC) (Fig. 2.2). The right liver usually has a larger
volume than the left liver (60:40), although this is
variable.
The second-order divisions (Figs 2.1 and 2.3) of
the hepatic artery supply four distinct zones of the
liver. Each is referred to as a section. The right liver
is divided into two sections, the right anterior sec-
tion and the right posterior section. These sections
are supplied by the right anterior sectional hepatic
artery and the right posterior sectional hepatic artery (Fig. 2.1). The plane between these sections is
the right intersectional plane. The right intersectional plane does not have any surface markings to
indicate its position. The left liver is also divided
into two sections, the left medial section and the
left lateral section (Fig. 2.3), which are supplied
by the left medial sectional hepatic artery and the
left lateral sectional hepatic artery (Fig. 2.1). The
plane between these sections is referred to as the left
intersectional plane. It does have surface markings
indicating its position – the umbilical fissure and
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Chapter 2
8
Anatomical
Couinaud segments
Term for
Diagram
7
4
d
6
Figure2.1 • Ramification of the hepatic artery in the
liver. The prevailing pattern is shown. The first-order
division of the proper hepatic artery is into the right
(a) and left (b) hepatic arteries, which supply right and
left hemilivers (Fig. 2.2), respectively. The secondorder division of the hepatic arteries, supplies the four
sections (Fig. 2.3). The third-order division, shown in
orange, supplies the segments (Fig. 2.4). Since the left
medial section and segment 4 are the same, the artery
is shown as being both sectional and segmental (red/
orange). The caudate lobe is supplied by branches
from (a) and (b). Bile duct anatomy and nomenclature
is similar to that of the hepatic artery. © Washington
University in St Louis.
c
AB
5
e
f
3
the line of attachment of the falciform ligament to
the anterior surface of the liver.
The third-order divisions of the hepatic artery
divide the right and left hemilivers into segments
(Sg) 2–8 (Figs 2.1 and 2.4). Each of the segments
has its own feeding segmental artery. The left lat-
2
eral section is divided into Sg2 and Sg3. The pattern or ramification of vessels within the left medial
section does not permit subdivision of this section
into segments, each with its own arterial blood supply. Therefore the left medial section and Sg4 are
synonymous. However, Sg4 is arbitrarily divided
into superior (4a) and inferior (4b) parts without
an exact anatomical plane of separation based on
internal ramification of vessels. The right anterior
section is divided into two segments, Sg5 and Sg8.
The right posterior section is divided into Sg6 and
Sg7. The planes between segments are referred to as
intersegmental planes. The ramifications of the bile
ducts are identical to that described for the arteries,
as are the zones of the liver drained by the respective ducts.
Segment 1 (caudate lobe) is a distinct portion of
the liver, separate from the right and left hemilivers
(Fig. 2.5). It is appropriately referred to as a lobe
since it is demarcated by visible fissures. It consists
of three parts: the bulbous left part (Spiegelian
lobe), which grips the left side of the vena cava and
is readily visible through the lesser omentum; the
paracaval portion, which lies anterior to the vena
term
Right hemiliver
or
Right liver
Left hemiliver
or
Left liver
Border or watershed: The border or watershed of the first-order division which separates the
two hemilivers is a plane which intersects the gallbladder fossa and the fossa for the IVC and is called the
midplane of the liver.
Figure2.2 • Nomenclature for first-order division anatomy (hemilivers or livers) and resections. © Washington
University in St Louis.
referred to
Sg5–8 (+/–Sg1)
Sg2–4 (+/–Sg1)
surgical resection
Right hepatectomy
or
Right hemihepatectomy
(stipulate +/– segment 1)
Left hepatectomy
or
Left hemihepatectomy
(stipulate +/– segment 1)
(pertinent area is shaded)
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7
6
7
6
4
5
8
4
5
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2
3
2
3
Hepatic, biliary and pancreatic anatomy
Second-order division
(second-order division based on bile ducts and hepatic artery)
Anatomical
term
Right anterior
section
Right posterior
section
Left medial
section
Left lateral
section
Couinaud segments
referred to
Sg 5,8
Sg 6,7
Sg 4
Sg 2,3
Term for
surgical resection
Add (-ectomy) to any of the
anatomical terms as in
Right anterior sectionectomy
Right posterior
sectionectomy
Left medial sectionectomy
or
Resection segment 4 (also see third order)
or
Segmentectomy 4 (also see third order)
Left lateral sectionectomy
or
Bisegmentectomy 2,3 (also see third order)
7
7
7
7
6
6
6
6
Diagram
8
5
8
5
8
5
8
5
2
4
3
2
4
3
2
4
3
2
4
3
(pertinent area is shaded)
Other sectional liver resections
Right trisectionectomy (preferred term)
Sg 4–8
(+/–Sg1)
Sg 2,3,4,5,8
(+/–Sg1)
Border or watershed: The borders or watersheds of the sections are planes referred to as the right and left
intersectional planes. The left intersectional plane passes through the umbilical fissure and the attachment
of the falciform ligament. There is no surface marking of the right intersectional plane.
Figure2.3 • Nomenclature for second-order division anatomy (sections) and resections including extended resections.
© Washington University in St Louis.
Extended right hepatectomy
Extended right hemihepatectomy
(stipulate +/– segment 1)
Left trisectionectomy (preferred term)
Extended left hepatectomy
Extended left hemihepatectomy
(stipulate +/– segment 1)
or
or
or
or
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7
5
6
8
7
5
6
2
4
3
2
4
3
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