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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_1520_Библиотеки_им_академика_М_И_Перельмана
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202
S. Jamdar et al.
randomized trial evidence comparing liver resection either to no intervention or to
systemic chemotherapy alone for patients with colorectal hepatic metastases [ 4 ] ,
ample evidence has accrued to indicate that a genuine survival advantage can be
achieved by liver resection, leaving the remnant liver clear of disease as compared
either to no systemic chemotherapy or “traditional” 5-fl uorouracil-based chemo-
therapy [
5 ] . Currently, newer biologic agents (in combination with other chemo-
therapy) given to patients who are identifi ed from genetic testing of their tumors can
achieve outstanding results.
Thus, the current focus of liver surgery for colorectal hepatic metastases involves
careful identifi cation of patients with liver disease, staging of local extent of disease
and remote metastatic burden, assessment of comorbidity, and then resection plan-
ning using either surgery alone or modifi cation of the future remnant liver (FRL) by
techniques such as portal vein embolization (PVE) or reduction of the volume of the
liver disease by neoadjuvant chemotherapy with the overall aim being to render the
liver free of metastatic disease.
15.2 Clinical Presentation
Colorectal liver metastases (CLM) are usually detected by surveillance of patients
with primary colorectal cancer. The impact of intensive surveillance on survival has
been demonstrated in a meta-analysis of strategies for colorectal cancer follow-up
[ 6 ] . Regular measurement of serum carcinoembryonic antigen (CEA) and abdomi-
nal computed tomography (CT) after curative resection of colorectal cancer leads to
earlier detection of recurrences and are associated with improved overall survival.
A similar benefi t has been demonstrated for intensive follow-up of patients
undergoing liver resection for hepatic colorectal metastases. Three monthly abdom-
inal CT scanning in the early period after index resection allows early detection of
recurrent disease. In a signifi cant number of patients, this will permit further surgi-
cal resection and improve survival [ 7 ] .
15.3 Evidence for Resection
No randomized controlled trial of hepatic resection for colorectal liver metastases
has ever been conducted, and there is therefore no level 1 evidence to recommend
this treatment. In particular, the capacity to cure patients of their disease has not
been clearly demonstrated within the context of a clinical trial. However, the weight
of clinical evidence suggests that cure is possible. This is supported by the fi ndings
of a systematic review of all published prospective single-center series of liver
resection for colorectal liver metastasis which shows that 30% of patients achieve
5-year survival after liver resection [
3 ] . Although relapse can still occur between 5
and 10 years, 20% of the population will still be alive after that point.
203
15 Colorectal Liver Metastases
15.4 Indications and Selection Criteria for Liver Resection
Criteria for liver resection are straightforward in principle – in a noncirrhotic liver,
resection of up to 75% of the parenchyma can be tolerated. However, in older
patients or those with comorbidity, it is wise to leave a greater functional remnant.
The functional remnant must have arterial and portal infl ow, adequate biliary drain-
age, and hepatic venous outfl ow. It is in this regard that a detailed knowledge of liver
segmental anatomy becomes important for resection.
Determination of resectability relies on detailed knowledge of liver anatomy as
described by Couinaud in 1957. The liver is divided into eight segments, each with
its own portal vein, hepatic artery, and bile duct and hepatic vein branches.
The parenchyma in the new remnant may be impaired in older patients because
of obesity (steatosis) or by prior chemotherapy. The FRL can be modifi ed by embo-
lization of the portal vein on the side to undergo resection. This leads to hypertrophy
of the contralateral lobe over a period of about 6 weeks.
The second major criterion is to exclude extrahepatic metastatic disease (see
below).
The third criterion takes into consideration the older age group of patients now
coming to surgery and comprises the objective assessment and categorization of
comorbidity.
It should be noted that the number of lesions does not in itself constitute an abso-
lute contraindication to resection although the location of disease is key – are there
suffi cient disease-free segments to sustain resection?
Current consensus dictates that at least two segments of the liver should remain
in the future liver remnant to allow satisfactory liver function while hepatic regen-
eration is in progress. Furthermore, the size of remnant liver should ideally be
20–30% of the total preoperative liver volume.
Selection criteria must acknowledge determinants of patient outcome, and with
this in mind, the clinical risk score (CRS) reported by Memorial Sloan-Kettering
Cancer Center in 1999 [
8 ] can be used to predict prognosis and to optimize pre-
operative staging. The score is based on the following fi ve parameters, which
were independent predictors of adverse prognosis in a series of 1,001 patients:
1. Node-positive primary tumor
2. Disease-free survival <12 months between colon resection and appearance of
liver metastases
3. More than one liver metastasis
4. Size of largest lesion >5 cm
5. CEA >200 ng/mL
The Sloan-Kettering clinical risk score has been independently validated and
assessed outside North American health care system, is easily remembered, and
should be widely used:
A CRS of <2 is associated with 5-year survival in excess of 50% provided the •
liver tumor burden is cleared.
204
S. Jamdar et al.
A CRS of 3 or 4 does not contraindicate resection, but surgery should be com-•
bined with adjuvant therapy.
A CRS of 5 identifi es a group in which long-term survivors are rarely •
encountered.
CRS can also be used to justify staging investigations – in particular, FDG-PET,
which should be considered in patients with a high CRS.
The indications and contraindications for resection of colorectal hepatic metas-
tases are shown in Box
15.1 .
15.5 Assessment for Liver Resection
Assessment has three essential components: assessment of comorbidity and fi tness
for surgery, staging of the extent of hepatic disease, and the detection of extrahe-
patic disease.
15.5.1 Assessment of Fitness for Surgery
Patients are offered surgical intervention on the basis that they have suffi cient
physiological reserve to undergo the stress of major surgery. In the past, the deci-
sion as to what constituted fi tness for surgery was based primarily on preoperative
clinical evaluation with selected preoperative investigation such as pulmonary
function tests and echocardiography. More recently, this process has been
improved by cardiopulmonary exercise testing (CPET). This is a noninvasive,
low-risk test of physiological response to increasing cardiovascular stress. During
incremental exercise, respiratory variables such as oxygen uptake and carbon
dioxide excretion are measured and ECG monitoring is performed. A report of the
use of CPET in 200 consecutive patients undergoing assessment for hepatectomy
Box 15.1: Indications and Contraindications to Liver Resection
Indications for resection
Resectable liver disease sparing a viable remnant liver (adequate infl ow, •
outfl ow, and biliary drainage).
No extrahepatic disease •
Patient fi t for major surgery •
Relative contraindications
Resectable local recurrence or resectable isolated extrahepatic disease, for •
example, spleen/adrenal
Resectable/ablatable lung metastases •
Resectable local direct extension of liver metastases, for example, dia-•
phragm/ adrenal
205
15 Colorectal Liver Metastases
demonstrated that a low anaerobic threshold (AT) was a useful predictor of adverse
outcome [ 9 ] .
15.5.2 Staging of the Extent of Hepatic Disease (See Chap. 10 )
15.5.2.1 Computed Tomography (Fig. 15.1 )
This is now the imaging modality of choice for the assessment of liver disease in
colorectal cancer. Use of intravenous iodinated contrast media and multiphase image
acquisition during contrast circulation through the liver provide high diagnostic
accuracy and give important information regarding the size, location, and proximity
to vascular structures of suspected metastases. The major limitations of this tech-
nique are the risks of exposure to ionizing radiation, the nephrotoxic effects of con-
trast media, and lower diagnostic accuracy for lesions smaller than 1 cm. In relation
to colorectal cancer, CT scanning should encompass the thorax, liver, and pelvis.
CT is useful in the initial hepatic staging of patients newly diagnosed with bowel
cancer; it is useful in surveillance after bowel cancer resection and can be invaluable
after liver resection when the presence of surgical clips can be a contraindication to
magnetic resonance scanning (Fig. 15.2 ). In addition to surveillance for further
metastatic disease, postresection CT is a good guide to regeneration and hypertro-
phy of the new remnant liver (Fig. 15.2 ).
15.5.2.2 Magnetic Resonance Imaging
Magnetic Resonance Imaging (MRI) is another highly effective imaging modality in
the assessment of liver lesions. It is generally considered a useful adjunct in the
Fig. 15.1 Contrast -enhanced
CT scan of the liver. This is a
portal venous phase fi lm with
contrast in the aorta, orally
administered contrast in the
stomach, and venous phase
contrast in hepatic veins.
There is a large hypodense
lesion occupying the right
lobe with a further lesion in
the periphery of the right
lobe. These lesions were
resected (in 2008) by
extended right hepatectomy –
correctly termed right
trisectionectomy
206
S. Jamdar et al.
assessment of hepatic metastases, particularly in sub-1-cm lesions. Metastases are
typically low signal on T1-weighted images. In contrast, on T2-weighted imaging
with fat suppression, they tend to be moderately high signal. The addition of liver-
specifi c contrast media has improved diagnostic performance. Gadolinium is distrib-
uted in blood vessels, and most colorectal metastases will appear as hypodense lesions
[ 10 ] . Gadolinium is regarded as an extracellular contrast agent. Agents such as super-
paramagnetic iron oxide (SPIO) are specifi cally taken by the hepatic Kupffer cells.
15.5.2.3 CT Compared to MRI
In practice, both modalities are used. CT is routine in surveillance. Once a lesion is
detected, there is evidence that contrast-enhanced MRI will provide greater sensi-
tivity: the range of reported sensitivities for CT is from 36% to 86%, whereas the
range for MRI is from 86% to 96% [ 10 ] .
MRI may also be preferred in the clinical setting of allergy to iodinated contrast
and severe liver steatosis.
15.5.3 Detection of Extrahepatic Disease
15.5.3.1 Positron Emission Tomography
This technique relies on increased glucose uptake in metabolically active cancer
tissues. [
18
F] fl uoro-2-deoxyglucose (FDG) administration is followed by Positron
Emission Tomography (PET) scanning which can be combined with CT scanning to
Fig. 15.2 CT scan after
classical right
hemihepatectomy. Note the
presence of surgical ligaclips
on the resection line together
with a small amount of
residual fl uid. The relative
hypertrophy of the caudate
lobe – segment 1 – is a good
indicator of liver regeneration
after resection
207
15 Colorectal Liver Metastases
provide excellent anatomical detail (Fig. 15.3 ). This modality has a high sensitivity
(typically in excess of 90%) [ 10 ] but a relatively low specifi city (40–50%) as any
metabolically active tissue (such as areas of infl ammation) will accumulate FDG
and potentially give a false-positive result (Figs. 15.4 and 15.5 ) .
15.6 Preresection Strategies
15.6.1 Neoadjuvant Chemotherapy
Results of the randomized phase III EORTC 40983 intergroup study (EPOC) [ 11 ]
demonstrate that perioperative neoadjuvant (pre- and postsurgery) chemotherapy
administered to patients with resectable liver metastases from colorectal cancer sig-
nifi cantly improves progression-free survival (PFS) compared to surgery alone. The
chemotherapy regimen used in the study was FOLFOX4 (oxaliplatin in combination
with 5-fl uorouracil/leucovorin). At a median follow-up of 3 years, FOLFOX4 treat-
ment given before and after surgery signifi cantly improved PFS by 9.2% and reduced
the risk of relapse by 27% ( HR = 0.73, p = 0.025) among patients who successfully
First scan Second scan First scan Second scan
Fig. 15.3 FDG -PET scan of liver. Isotope images ( top row ) are superimposed on CT scan images
( middle row ) with color enhancement to produce the typical PET images ( lower row ). Hepatic
metastases are typically intensely PET-avid. Care must be taken to exclude false-positive results
from area of persistent collections, for example, residual pelvic collections after the primary bowel
operation and also some histological subtypes of colon cancer – typically mucinous tumors – pro-
duce much less metabolically active metastases and are thus much less PET-avid
208
S. Jamdar et al.
underwent resection. Results also showed that FOLFOX4 given before resection did
not compromise fi tness to undergo surgery. In terms of morbidity and mortality
associated with perioperative chemotherapy, the complication rate in patients under-
going surgery with perioperative chemotherapy was 25.2% compared with 15.9% in
the surgery alone arm ( p = 0.04). The operative mortality was low (<1%), regardless
of treatment group allocation: two deaths after surgery in the surgery alone group
and one in the surgery plus chemotherapy group.
15.6.2 Portal Vein Embolization
The intention of PVE is to induce atrophy of the liver which requires resection in
the expectation that the intended liver remnant will hypertrophy. This strategy aims
Patient with suspected
colorectal hepatic metastasis:
Detailed pre-resection
work-up
Potentially fit for surgery
Unfit for surgery
Chemotheraphy
Consider chemotheraphy
Thoracic disease not
amenable to resection
and/or extrahepatic
disease
CPEt
(Functional
Test of cardio-
pulmonary reserve)
No thoracic or
pelvic diasease
Recent clear
colonoscopy
Assessment of co-morbidity
CT liver
CT pelvis
CT thorax
± colonoscopy
Baseline
disease staging
Fig. 15.4 Staging algorithm – general assessment of patient with suspected colorectal hepatic
metastases
209
15 Colorectal Liver Metastases
to avoid postoperative liver failure particularly in patients undergoing extended
resections. The technique can be performed as a percutaneous intervention under
ultrasonographic and fl uoroscopic guidance or at surgery. Following embolization,
a period of 6 weeks is usually allowed before repeat volumetric assessment of the
liver is undertaken.
15.7 Operative Technique
The principles of liver resection are now well established and rely on adequate
mobilization of the liver, control of the infl ow at the liver hilum, mobilization of
the liver from the inferior vena cava, and control of the hepatic venous outfl ow.
Liver parenchymal transection is usually undertaken with low central venous
pressure, and a variety of transection devices are available. Probably, the most
widely used technique is the CUSA (cavitron ultrasonic suction aspirator) which
uses a high-frequency ultrasonic vibrating tip to destroy parenchyma which is
Gadolinium
(Primovist) MR
• Tumour burden
resectable by
hepatectomy of up to
75% in non-cirrhotic
(± Preop portal vein
embolization)
Hepatectomy
• CRS > 2.
Additional pre-resection
staging.
• FDG-PET
• ± Laparoscopy
R0 resection
feasible
(± PVE)
Chemotherapy
Extrahepatic
disease
Fig. 15.5 Detailed
preresection assessment
210
S. Jamdar et al.
then aspirated through a suction channel. Firmer structures within the paren-
chyma such as major vascular pedicles are exposed and can be ligated. The
combination of CUSA, low CVP, and electrocautery can allow a very safe “dry”
transection of the liver parenchyma without the need for routine blood
transfusion.
A detailed discussion of liver resection terminology is outwith the scope of this
chapter, but a succinct summary is relevant. Liver resection terminology was stan-
dardized at the Brisbane consensus meeting in 2000 [
12 ] . Resection of the anatomi-
cal right hemiliver involves resection of the right anterior section (segments 5 and 8)
and the right posterior section (segments 6 and 7). Thus, right hemihepatectomy
could also be called right bisectionectomy. The relevance is that if the full anatomical
right lobe is resected up to the falciform ligament (adding segment Iva and IVb – the
left medial section – to the right hemiliver), the operation is then termed a right
trisectionectomy.
While complex, this terminology has been widely adopted and allowed for stan-
dardization of liver resectional nomenclature.
15.7.1 Relevance of Resection Margin
There is now good evidence that complete oncological resection is the key. Provided
the metastasis is completely removed, there is no additional benefi t to be accrued
from having a 1-cm resection margin [ 13 ] . These fi ndings have important practical
implications when surgery is being undertaken for colorectal hepatic metastases as
nonanatomical metastasectomy can be considered as a viable alternative to classical
hemihepatectomy: this procedure preserves liver parenchyma and may facilitate
future redo liver resection.
15.7.2 Laparoscopic Liver Resection
Laparoscopic techniques can be readily adapted to liver resection. The operation
of left lobectomy (strictly termed left lateral sectionectomy) requires division of
the left lobe infl ow and the left hepatic vein with a relatively small amount of
parenchyma. This operation is now regularly performed laparoscopically. A
consensus conference held in the United States, the “Louisville consensus,”
accepted that laparoscopic liver surgery was an established component of liver
surgery and defi ned lesions in the periphery (segments 2–6) and in the left lobe
as suitable for this approach [ 14 ] . Laparoscopic resection of the left lobe was
termed “standard practice” [ 14 ] . It is likely that indications will broaden with
the gaining of experience.
211
15 Colorectal Liver Metastases
15.7.3 Timing of Liver Resection in Relation
to Colonic Resection
Traditionally, the colonic resection was undertaken as the fi rst or index operation
with liver resection being undertaken several months later in the case of patients
presenting with synchronous bowel and liver metastases or the liver resection being
undertaken many months after surgery in those patients presenting with late liver
metastases.
This paradigm has been changed by the results of large-scale randomized clinical
trials demonstrating a survival benefi t from preoperative radiotherapy in patients
with rectal cancer [ 15 ] and from combination of radiotherapy with 5-fl uorouracil-
based chemotherapy [ 16 ] .
Thus, in modern multidisciplinary management, a case can be made for liver
resection as the fi rst oncological intervention with operation being undertaken
before systemic chemotherapy and local radiotherapy for the primary tumor. This
approach can be considered if there is hepatic metastatic disease at the borderline
for resection where delay may make disease unresectable – for example, disease
close to the hepatic vein/caval confl uence or to facilitate staged liver resection.
An alternative treatment option is synchronous resection. This is where the liver
resection and the bowel resection are undertaken at the same operation. While this
has the disadvantage of subjecting the patient to a more intense surgical procedure,
it avoids the need for two procedures and allows patients to proceed directly to
adjuvant chemotherapy [ 17 ] . There is as yet little published evidence to support this
strategy, but it can be considered when the combination of a relatively “minor” liver
resection with a colonic resection will render the patient free of synchronous bowel
primary disease with hepatic metastases.
Finally, neoadjuvant chemotherapy can be used to “downstage” potentially unre-
sectable disease – making lesions smaller can facilitate resection [ 18 ] . With down-
staging chemotherapy, lesions may disappear completely, and there remains
controversy as to whether these areas of liver parenchyma which have carried tumors
should be resected.
15.7.4 Survival and Outcome After Liver Resection
In contemporary liver surgical practice, hepatectomy for colorectal hepatic meta-
static disease can be accomplished with low mortality. More frequently seen com-
plications include biliary leakage from the cut surface and pleural effusion.
Long-term survival data were reported from a prospectively maintained single-insti-
tutional database with 455 consecutive patients undergoing liver resection [ 19 ] . The
actuarial median overall survival was 33 months (95% CI, 29–37%), and actuarial
5- and 10-year survival rates were 34% and 25%, respectively [ 19 ] . Similar data are
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