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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_992_Библиотеки_им_академика_М_И_Перельмана.pdf
Chapter 6
contrast circulation in the liver.7 During the portal
venous phase, normal liver parenchyma usually
enhances intensely while liver metastases (with
their dominant arterial supply) appear as relatively
hypodense hypovascular lesions. In small-sized liver
metastases, arterial dominant phase imaging may be
useful to detect faint peripheral rim enhancement.
Delayed images should be obtained 4–5 minutes
after contrast injection. This is helpful in differenti-
ating metastases from benign liver lesions, particu-
larly a haemangioma.8 Whilst CT is considered a
standard of care, it has limitations, including the
need for a high radiation dose and low sensitivity
for the detection and characterisation of lesions
smaller than 1 cm (Figs 6.1–6.6).
Magnetic resonance imaging (MRI)
MRI is a highly effective imaging modality for
detecting and characterising liver lesions and
provides high lesion-to-liver contrast without
using ionising radiation. Typically, CRLMs show
low signal intensity on T1-weighted images and
moderately high signal intensity on T2-weighted
images with fat suppression. Gadolinium, the
most commonly used MRI contrast agent, behaves
similarly to the iodinated contrast agents used in
CT. Liver-specific contrast media such as superparamagnetic iron oxide (SPIO), gadoxetic acid
(Primovist®) and Mangafodipir trisodium (Mn
DPDP, Teslascan) are not taken up by colorectal
hepatic metastases, so may aid in the detection of
CRLMs.
9,10
These agents are of particular value
in the characterisation of liver lesions that are
either small or indeterminate on other imaging
modalities.
8,10
Whilst the benefits of MRI are evident, it does have
a number of limitations. MRI has a low sensitivity for detecting extrahepatic disease in the peritoneum and chest, and takes longer to perform than
a b
c
Figure6.1 • (a) CT image in the portal-venous phase demonstrating a hypodense colorectal liver metastasis occupying
segments 2 and 3. (b) PET-CT image of the same metastasis demonstrating high uptake of FDG. (c) T1-weighted MRI
image of the same metastasis demonstrating a typical hypodense colorectal metastasis. (d) T1-weighted MRI image
following primovist contrast administration. Evidence of contrast take-up within the liver and excretion within the common
bile duct is observed. No evidence of contrast take-up within the metastasis can be seen.
d
110
Colorectal liver metastases
a
c
b
d
e
Figure6.2 • (a) T1-weighted MRI image without contrast demonstrating a typical hypodense metastasis in segment 6.
(b) T2-weighted MRI image of the same metastasis, where the metastasis is brighter than the surrounding liver. Evidence
of central necrosis is seen as a brighter central area of the metastasis. (c) T1-weighted MRI image with fat suppression
before contrast administration. (d) T1-weighted MRI image with fat suppression in the arterial phase following primovist
contrast administration. The metastasis demonstrates typical rim enhancement. (e) T1-weighted MRI image with fat
suppression following primovist contrast administration in the portal venous phase. Good contrast take-up within the liver
is observed. (f) T1-weighted MRI image with fat suppression 20 minutes following primovist contrast administration. No
evidence of contrast take-up within the metastasis is seen. Evidence of contrast excretion within the gallbladder, common
bile duct and kidney can be observed.
f
111
Chapter 6
Figure6.3 • Images extracted from a PET-CT scan demonstrating CT, PET and fused PET-CT images of a liver
metastasis in the right liver.
contrast-enhanced CT. There are also a number of
contraindications to MRI, including patients with
pacemakers, implantable cardiac defibrillators, cochlear implants and metallic orbital foreign bodies.10
However, it can be used safely in patients with allergies to iodinated contrast agents (Figs 6.1 and 6.2).
Positron emission tomography (PET)
PET has emerged as an important diagnostic tool
in the evaluation of CRLMs. Colorectal malignancies are often metabolically active and therefore have a greater glucose uptake relative to that
of surrounding normal tissues. This can be identified with [18F]fluoro-2-d-glucose (FDG-PET).
This modality is highly sensitive, especially when
combined with CT.11 PET-CT is often used in the
preoperative assessment of CRLMs, often with
the aim of identifying irresectable extrahepatic
disease that would make liver resection futile.12
It can sometimes be difficult to differentiate
between malignant tissue and other metabolically active tissue, e.g. inflammatory tissue due
to infective or postsurgical causes.12 Mucinous
colorectal metastases may also prove difficult to
detect due to reduced glucose uptake.13 Other
disadvantages of PET include high cost and
limited sensitivity for lesions smaller than 1 cm
(Figs 6.1 and 6.3–6.6).
Staging laparoscopy
The role of staging laparoscopy has evolved as
radiology has improved and criteria for resection have changed. However, staging laparoscopy
may be useful for the detection of unresectable
peritoneal disease not detected by conventional
radiology.
The yield of laparoscopy for detecting unresectable disease varies from 6% to 36%.
13–19
112
Staging
Colorectal liver metastases
Figure6.4 • Images extracted from a PET-CT scan demonstrating CT, PET and fused PET-CT images of a PET-positive
primary rectal cancer. Evidence of a left lobe liver metastasis can be seen in the bottom right image.
laparoscopy cannot be performed in 6–16% of patients due to adhesions from previous surgery.
13–19
One study suggested that staging laparoscopy had
whilst there may be a role for staging laparoscopy
in selected high-risk individuals, its routine use for
all patients cannot be justified.
greater value in those patients with a higher clinical risk score (CRS).20 The CRS ranges from 0 to
Cardiopulmonary exercise testing
5 based on the presence of the following characteristics: node-positive primary tumour, prehepatectomy carcinoembryonic antigen (CEA) greater than
200 ng/mL, more than one liver tumour, liver tumour
size greater than 5 cm and disease-free interval of less
than 1 year. In a Memorial Sloan Kettering Cancer
Center study,20 only 4% of patients with CRS of
0–1 were irresectable and none were identified as
unresectable at preoperative laparoscopy. At scores
of 2–3, 21% of lesions were unresectable and only
one-half were found at laparoscopy (yield of 11%).
The highest yield was at scores of 4–5, where the
yield of laparoscopy was 24%.
The value of staging laparoscopy is likely to have
diminished with recent advances in imaging and
an expanding view of what is resectable disease, so
Traditionally, selection of patients for resection has
been centred on identifying patients with resectable
disease. Recently interest has grown in identifying
patients who have a higher operative risk, either
from reduced fitness or previously unknown cardiorespiratory comorbidities. Cardiopulmonary exercise testing (CPET) has been shown to be useful
in quantifying surgical risk in patients undergoing
major hepatobiliary surgery.21 Given that patients
over the age of 70 are known to have significantly
higher operative risk
22,23
and that 50% of patients
diagnosed with colorectal cancer are over 70, this
technique may have a role to play in the appropriate
selection and management of patients undergoing
liver resection.
113
Chapter 6
Figure6.5 • Images extracted from a PET-CT scan demonstrating CT, PET and fused PET-CT images of a PET-positive
nodal mass in the left superior mediastinum.
Contrast-enhanced CT should be performed
in the assessment of all patients with colorectal liver
metastasis. Further assessment of liver metastases
varies depending on local expertise and availability
of other modalities. MRI and PET-CT are useful to
characterise hepatic lesions and assess the extent
of extrahepatic disease.
4
Surgery: the old and the new standards for resection
three unilobar metastases, preferably presenting
at least 12 months after resection of the primary
tumour, whose disease was resectable with at
least a 1-cm margin of healthy liver tissue and
who had no hilar lymphadenopathy or extrahepatic disease.
Recent experience has demonstrated that patients
outside these narrow parameters can experience
long-term survival following liver resection.
24,25
Modern criteria for resection are now based on
whether a macroscopically complete resection of
the disease can be achieved. Instead of resectability
being defined by what is removed, resectability is
Criteria for resection
now being determined by what will remain.
In 2006, consensus statements from the American
If CRLMs are resectable, patients can look forward to a 5-year survival of 40–50% and a 10year survival of 24%, with age being no barrier to
resection if fit (Fig. 6.7). In the past, liver resection
was attempted only in patients who had one to
Hepato-Pancreato-Biliary Association (AHPBA)
and a pan-European group changed the criteria for
resection.
5,26
The American consensus suggested
CRLMs should be considered resectable if (i) the
disease can be completely resected (regardless of
114
Colorectal liver metastases
Patient survival after a 1st hepatectomy for
Figure6.6 • Images extracted from a PET-CT scan demonstrating CT, PET and fused PET-CT images of a right lower
lobe PET-positive lung metastasis.
colorectal metastases: 11384 patients
100
90
80
70
60
50
40
30
20
10
0
012345678910
Age 70 <70 years>=70 years
Figure6.7 • LiverMetSurvey. Ten-year survival following
hepatectomy for CRLMs comparing patients <70 years
of age with those >70 years of age. Reproduced with
permission.
Log rank P=<0.0001
margin), (ii) two adjacent liver segments can be
spared with adequate vascular inflow and outflow
and biliary drainage, and (iii) the volume of the
liver remaining after resection, i.e. the ‘future liver
remnant’ (FLR), will be adequate.5 The European
group concluded that criteria rendering patients irresectable included invasion of one branch of the
liver pedicle and contact with the contralateral
branch, contact with the inferior vena cava, invasion of all three hepatic veins, the presence of coeliac lymph nodes and the presence of non-resectable
extrahepatic disease.26 These criteria have already
been challenged with long-term survival in patients
undergoing nodal resection and resection of metastasis involving the inferior vena cava (IVC).
27,28
Resection has also been performed for lesions involving all three hepatic veins, though long-term
survival data are not available.
29
115
Chapter 6
The 2011 UK national guidance recommended that
resection should be offered if a patient is fit enough,
and complete resection can be achieved whilst leaving an adequate future liver remnant.4 There are no
absolute contraindications to resection issued in this
guidance, but in normal circumstances they recommend that contraindications to liver resection are:
1. Non-treatable primary tumour
2. Widespread pulmonary disease
3. Locoregional recurrence
4. Uncontrollable peritoneal disease
5. Extensive nodal disease, such as retroperitoneal
or mediastinal lymph nodes
6. Bone or CNS metastases.
Without resection very few patients with
colorectal liver metastases are alive 5 years after
their detection.
3
Surgical strategies to improve resectability
A variety of strategies have been employed to bring patients with unresectable disease to surgical resection.
Portal vein embolisation
a one-stage resection of all the involved segments
would lead to liver failure.34 The first stage involves
resection of metastases from the FLR and PVE (or
portal vein ligation during surgery), followed by a
period of liver regeneration and hypertrophy of the
FLR alongside systemic chemotherapy. The second
stage is performed 2–3 months later and consists
of the major hepatectomy to remove the residual
disease. A large series reported 1- and 3-year survival of 70.0% and 54.4%, respectively, in 25 of
33 patients in whom a two-stage hepatectomy could
be completed.35 There was no operative mortality;
postoperative morbidity was 15.1% and 56.0% after first- and second-stage hepatectomy, respectively.
Repeat hepatectomy
Repeat hepatectomy for patients with colorectal
liver metastases is safe and provides survival benefit. A meta-analysis of 21 studies, comprising 3741
patients, showed that there was no difference in
perioperative morbidity, mortality or long-term survival between patients undergoing a first or repeat
hepatectomy.36 A study looking at 1706 patients
undergoing repeat hepatectomy for CRLMs demonstrated similar morbidity and mortality after third
and fourth hepatectomies, though 5-year survival
decreased from 47.1% for a first resection to 23.8%
for a third or fourth resection.
37
Portal vein embolisation (PVE) induces atrophy of
the liver to be resected and hypertrophy of the liver
that will remain (i.e. increases the future liver remnant), with the aim of avoiding post-resection hepatic
insufficiency, liver failure and death. A meta-analysis
of 1088 patients confirmed that this technique significantly increased the FLR, making more patients suitable for liver resection.30 The overall morbidity rate
was 2.2% without mortality. Following PVE, 930
patients (85%) proceeded to laparotomy. Resection
was not performed in 158 patients (17%): in 131 because of inadequate hypertrophy of the FLR and in
27 because of disease progression.
Although there is no consensus on what consti-
tutes a safe volume of remnant liver, minimum values of 20–25% for patients with normal livers, 30%
following neoadjuvant chemotherapy and 40% in
the presence of chronic liver disease have been sug-
5,31,32
gested.
bined with neoadjuvant chemotherapy.
PVE also appears to be safe when com-
33
Two-stage hepatectomy
Two-stage hepatectomy involves delayed rehepatectomy after hypertrophy of the residual liver
and may be used for large bilateral lesions in which
Extreme liver surgery
Resection of tumours involving the hepatic vascular
inflow has been described, including portal vein resection and reconstruction, hepatic artery resection
and reconstruction (or arterialisation of the portal
vein as an alternative).38 Resections of tumours with
involvement of the IVC or the three major hepatic
veins have also been performed, using techniques
such as total hepatic vascular exclusion, in situ hypothermic perfusion and ex vivo (bench) hepatic
resection.
of what is currently feasible and are associated with
significant morbidity and mortality. Nonetheless,
this aggressive surgical approach may offer hope for
patients with hepatic tumours involving the IVC,
who would otherwise have a poor prognosis.
39–41
These techniques are at the frontier
Extrahepatic colorectal disease
Extrahepatic colorectal metastases, such as direct
diaphragmatic invasion, adrenal metastases and
lung metastases, may be resected with curative intent. Reported long-term survival after pneumonectomy for colorectal metastases mirrors very
closely that seen after hepatectomy, with most series
116
Colorectal liver metastases
quoting a 5-year survival of the order of 40–50%,
with similar low operative morbidity and mortal-
42–45
ity.
More recent series have identified 5-year
survival approaching 70%46 and showed that repeat resection of pulmonary metastases is also of
benefit, with 5-year survival of 42% following second pneumonectomy.
47
Other series looking at liver resection in the presence of extrahepatic disease have demonstrated that
there is a role for resection of other limited extraheptic disease, including peritoneal, hepatic pedicle
nodal disease, aortocaval nodal disease, ovarian and
bone metastases.
28,48,49
Five-year survival following
limited peritoneal and hepatic pedicle nodal disease is
quoted at 27% and 26%, respectively.48 Aortocaval
nodal disease is associated with worse long-term survival, with a 5-year survival of just 7%.
There are no absolute contraindications to
surgical resection of colorectal liver metastases as
long as the disease can be fully resected (including
extrahepatic disease). The use of advanced
surgical techniques may bring patients previously
considered irresectable to surgery with curative
4,30–41
intent.
49
Techniques of surgical resection
Transection techniques
Technological innovations in liver surgery have
mainly focused on minimising blood loss during
transection of the hepatic parenchyma, as blood
transfusion is associated with increased postoperative morbidity and mortality, as well as reduced
long-term survival.50 Inflow occlusion (Pringle manoeuvre) and low central venous pressure (CVP)
anaesthesia minimise blood loss but may cause
liver damage by ischaemia and reperfusion injury.
Consequently, there has been an interest in devices
that facilitate a more bloodless liver transection,
obviating the need for inflow occlusion associated
with the traditional clamp-crushing technique.
The most popular of these techniques include the
ultrasonic aspirating dissector (CUSA) using ultrasonic energy, the Hydrojet using a pressurised jet
of water and the dissecting sealer (TissueLink) using radiofrequency energy. These techniques were
compared in a randomised controlled trial51 and in a
subsequent Cochrane review.52 There was little difference demonstrated between the four techniques,
though the clamp-crushing technique was found
to be associated with faster tissue transection and
lower transfusion requirements. The Cochrane review also found an association with fewer infective
complications. Both studies highlighted the significantly reduced cost associated with the clampcrushing technique, and therefore could not advocate
the use of newer techniques in standard practice.
A further randomised control trial of radiofrequency-assisted versus clamp-crushing transection
in 50 patients showed a higher rate of postoperative
complications in the radiofrequency group (20%),
compared to none in the clamp-crushing group.
53
Fibrin sealants
Fibrin sealants have become popular as a means
of improving perioperative haemostasis and reducing biliary leakage after liver surgery. However, a
randomised study of 300 patients showed no differences in transfusion requirement, overall drainage,
incidence of biliary fistula and postoperative morbidity between those receiving fibrin glue application and controls.54 Similar to the newer transection
techniques, there is little evidence to justify the fibrin sealants, especially given the financial pressures
on healthcare provision.
Laparoscopic liver surgery: less is more?
Laparoscopic surgery for hepatic neoplasms aims
to provide curative resection while minimising complications. There are no randomised controlled trials assessing the use of laparoscopic hepatectomy
and the evidence is based on retrospective series.
A meta-analysis of series published between 1998
and 200555 included eight non-randomised studies,
reporting on 409 resections of hepatic neoplasms,
of which 165 (40.3%) were laparoscopic and 244
(59.7%) were open. Operative blood loss and duration of hospital stay were reduced significantly
after laparoscopic surgery. These findings remained
consistent when considering studies matched for
the presence of malignancy and segment resection.
There was no difference in postoperative adverse
events and extent of oncological clearance. This
paper concluded that laparoscopic liver resection
has the potential to reduce operative blood loss and
allow earlier recovery with oncological clearance
comparable with open surgery.
The largest single-centre experience of laparoscopic resection of CRLMs included 83 resections
within a series of 133 liver resections.56 Resections
comprised 42 wedge excisions, 10 segmentectomies,
nine bisegmentectomies, three trisegmentectomies,
30 left lateral segmentectomies, four left hepatectomies, 31 right hepatectomies, three extended right
hepatectomies and two caudate lobe resections.
The authors reported a median operating time of
117
Chapter 6
210 minutes (30–480 minutes), median blood loss
of 300 mL (10–3000 mL) and a median postoperative stay of 4 days (1–15 days). Severe postoperative
bleeding occurred in five patients (3.7%), requiring intensive care management or re-operation, and
overall serious complications occurred in 16 patients
(13%). Microscopically negative margins (R0/R1)
were achieved in 96% of patients with CRLMs.
In 2008 a group of 45 experts in hepatobiliary
surgery participated in a consensus conference and
concluded that the laparoscopic approach to liver
resection is a safe and effective technique for appropriately trained surgeons.
The current evidence for laparoscopic liver resection is based on selective case series. Despite this,
laparoscopic surgery has the potential to reduce operative blood loss and aid in earlier recovery, with
oncological clearance comparable with open surgery. Randomised controlled trials would be useful
to strengthen the evidence base and aid selection of
appropriate cases.
57
Morbidity, mortality and survival after liver resection for CRLMs
The utility of surgical resection of CRLMs is clearly
established. Prospective and retrospective studies
consistently show 5-year survival rates following
liver resection of 30–50%, depending on selection
criteria. A major systematic review of surgical resection for CRLMs was undertaken to assess the published evidence for its efficacy and safety and to
identify prognostic factors.58 Thirty independent
studies met all the eligibility criteria for the review
and data on 30-day mortality and morbidity were included from a further nine studies. The best available
evidence came from prospective case series, but only
two studies reported outcomes for all patients undergoing surgery. The remainder reported outcomes for
selected groups of patients: those undergoing hepatic
resection or those undergoing curative resection.
Death within 30 days of hepatic resection was reported by 24 studies and ranged from 0% to 6.6%
(median 2.8%). A further nine studies reported perioperative mortality within an undefined time period
(1.3–4.6%, median 3.6%) and two studies reported
60-day mortality (3.4–5.5%). Mortality was not
reported in four studies. Cause of death was reported in 15 studies for a total of 103 patients. The
commonest specified causes of fatal complications
were, in descending order of frequency: hepatic failure, postoperative haemorrhage, generalised sepsis,
cardiac failure, multiorgan failure, pulmonary embolism, bile leak and anastomotic leak.
58
Perioperative complications, including indicators
of morbidity such as length of hospital stay, were reported in 29 studies. Commonest causes of morbidity, in descending order of frequency, were: wound
infection (5.4%), generalised sepsis (4.6%), pleural
effusion (4.3%), bile leak (4.0%), perihepatic abscess (3.0%), hepatic failure (2.8%), arrhythmia
(2.8%), postoperative haemorrhage (2.7%), cardiac
failure (2.4%) and pneumonia (1.9%).
Studies in which it was unclear whether resections
were R0 or R1/2, or only presented data for both
types of resection combined, had a median 5-year
survival of 32% (9–63%). Sixteen studies presented
5-year survival for patients undergoing R0 resection, either for the whole study population or for
subgroups of patients. Median 5-year survival for
these studies was 30% (range 15–67%). Eleven studies reporting 5-year survival for non-radical resections had a median 5-year survival of 7.2% (range
0–30%) and six studies reporting patients who did
not undergo resection had a median 5-year survival
of 0% (range 0–6%). Disease-free survival was reported by fewer studies. Median disease-free survival
was 14.3 months for radically resected patients and
17.2 months for patients with unspecified resections.
Twenty-two per cent of all patients experienced
recurrence in the liver only, although this is likely
to be underestimated as two studies did not specify
the proportion of liver-only recurrences. Liver plus
extrahepatic recurrences and extrahepatic-only recurrences were experienced by 16% and 24% of patients, respectively. In addition, one study reported
recurrences in 235 (62.5%) radically resected patients, although sites of recurrence were not specified.
This systematic review was undertaken because
ascertaining the benefits of surgical resection of
CRLMs is difficult in the absence of randomised
trials. However, it is clear that there is a biologically distinct group of patients with liver metastases
who may become long-term disease-free survivors
following hepatic resection. Such survival is rare in
apparently comparable patients who do not have
surgical treatment.
Classification of CRLMs
Staging systems and terminology
The present American Joint Committee on Cancer
(AJCC) classifies all colorectal metastasis beyond the
local lymphatic basin as stage IV colorectal cancer.
This does not allow the distinction between patients
who are currently incurable, with a prognosis of less
than 6 months, from those who are potentially curable. This has led to the call for a new staging system for colorectal cancer that reflects these differing
118
Colorectal liver metastases
treatment pathways and prognostic outlook.59
The 2003 French guidelines on the management of
CRLMs recommended four categories that could be
defined: (1) easily resectable liver metastases, (2) resectable liver metastases involving five to six liver segments and/or contralateral major vascular structures,
(3) liver metastases that are initially unresectable but
may become resectable after chemotherapy, and (4)
definitely unresectable.60 Based on the French classification system, the European Colorectal Metastases
Treatment group has proposed a staging system:
26
• IVa–easilyresectablewithcurativeintentat
detection (French classification 1);
• IVb–technicallydifficult/borderlineresectable
at detection (French classification 2);
• IVc–potentiallyresectableafterneotherapeutic
chemotherapy (French classification 3);
• IVd–littleornohopeofbeingrendered
resectable with curative intent after conventional
chemotherapy (French classification 4);
• Va–resectableextrahepaticdisease;
• Vb–unresectableextrahepaticdisease.
Other suggested systems include distinguishing
between stage IV-R for patients with resectable disease and stage IV-U for patients with unresectable
disease.61 Furthermore, stage IV-R could be further
divided into IV-Ra (resectable liver only), IV-Rb
(resectable extrahepatic only) and IV-Rc (resectable
hepatic and extrahepatic). Stage IV-U could be similarly subdivided, after assessment by an experienced
site-specific surgical oncologist.
A number of scoring systems have been developed
that take a different approach to the staging of
CRLMs and attempt to classify patients based on
clinical prognosis. The most popular of these were
produced by Fong et al.,20 Nordlinger et al.62 and
Rees et al.63 The Fong classification (clinical risk
score) was described earlier and is the most widely
used owing to its ease of use. Nordlinger's classification ranges from 0 to 7, with 1 point being awarded
for each of the following adverse risk factors:
1. Extension into serosa of primary tumour
2. Lymphatic spread of the primary tumour
3. Delay from primary tumour to resection
<24 months
4. Number of liver metastases in preoperative
imaging
5. Largest size of liver metastasis in preoperative
imaging ≥5.0 cm
6. Preoperatively estimated clearance of normal
parenchyma resected with liver metastasis <1 cm
7. Age ≥60.
These two scoring systems have been com-
64,65
pared,
with the Fong classification proving to be
more appropriate for use in clinical practice and better at differentiating between groups. Both scoring
systems exclude patients with extrahepatic disease
and fail to take into account many known adverse
risk factors, meaning that their clinical utility may
be limited.
Rees et al. proposed a scoring system that could
be used in either the preoperative or postoperative setting.63 In this risk prediction model, points
were allocated up to a maximum of 30 (Table 6.1).
Patients with a score of 0, 10, 20 and 30 on
preoperative scoring had 5-year survival rates of
66%, 35%, 12% and 2%, respectively. This compared very well with the scores determined postoperatively. This scoring system is more complex than
previously suggested models, which has limited its
uptake as a clinical tool.
Table6.1 • Basingstoke Predictive Index (BPI) of long-term
cancer-specific survival after primary hepatic
resection for colorectal liver metastasis
Risk factor Preoperative Postoperative
Primary tumour lymph node status
Negative 0 0
Positive 2 2
Primary tumour differentiation
Well 0 0
Moderate 3 2
Poor 5 4
CEA at hepatectomy
<6 ng/mL 0 0
6–60 ng/mL 2 1
>60 ng/mL 3 3
Number of hepatic metastases
1–3 0 n/a
>3 4 n/a
Largest tumour diameter
<5 cm 0 0
5–10 cm 2 2
>10 cm 8 7
Hepatic resection margin
Negative n/a 0
Positive n/a 11
Extrahepatic disease
No 0 0
Yes 7 4
119