surgical manag of colorectal liver mets

Surgical management of
Colorectal liver metastasis
Dr Dharma Poonia

• Background, epidemiology.
• Patient selection and assessment.
• Prognostic variables.
• Define resectability.
• Methods to increase resectability.
• Adjunct methods.
• Recent development.

Background, epidemiology.
• It is 3rd MC cancer in men and 2nd MC cancer
in women in western world.
• 80% of patients with colorectal cancer (CRC)
present with local or regional disease.
• For these patients, the general plan of
treatment is clear: surgery with the intent of
cure.

• Remaining 20% of newly diagnosed patients
continue to present with synchronously
diagnosed stage 4 disease.
• 25% patients with primary colorectal
carcinoma present with synchronous hepatic
metastasis, and 50% of the patients will
eventually develop metachronous liver
metastasis
» (Bozzetti et al, 1987; Ekberg et al, 1987).

• For these patients, the treatment plan is less
obvious.
• Despite their advanced stage of disease, a
subset of stage 4 patients are potentially
curable.

• The liver is the most common site for
hematogenous metastasis from colorectal
cancers (CRCs).
• In patients with isolated hepatic metastases,
the extent of liver disease is the principal
determinant of survival, and when left
untreated, survival is measured in months
» (Norstein & Silen, 1997).

• Following resection for CRLM, 5 years OS is 40%,
with a 10-year survival approaching 20%.
• No PRTCs comparing liver resection to systemic,
regional, or other local therapies have been
performed, the outcome for patients after liver
resection for metastatic CRC is sufficiently
favorable that surgery is now considered the
primary therapy in selected patients
» Pawlik & Choti, 2007; Ito et al, 2010).

• With newer multimodal treatments and
careful patient selection, it is anticipated that
5-year survival approaching 70% can be
achieved after resection and comparable
outcomes are likely to be reported in larger
studies in the near future.
» (Nikfarjam et al, 2009)

What are the options for patients with
colorectal liver metastasis?
• Do nothing
– median survival of 6 to 9 months.
• Chemotherapy
– 14.5-month median survival,
• RFA
– 40% 3-year survival rate,
• Resection
– 5-year survival rate of 45% to 60%

Patient selection & assessment

• Standard staging by AJCC did not provide
prognostic informations.
• Therefore, a classification system that can
discriminate between these patients and
provide additional prognostic information is
paramount.

• Prognostic variables
1) clinical and pathologic variables associated with
the primary tumor;
2) clinical variables associated with the liver
metastases, such as response to neoadjuvant
chemotherapy; and
3) pathologic characteristics of the liver
metastases.

• There was no single factor other than incomplete
resection that absolutely and reliably precluded
survival.
• Current risk-scoring systems permit stratification
of expected outcomes and identify patients with
low probability of survival.
• However, these systems do not identify patients
whose survival is certain and preclude
consideration for adjuvant therapy

surgical manag of colorectal liver mets

Predictive Models and Clinical Risk
Scores
• Four large studies on multivariate analyses of
prognostic factors designed a of useful
predictive models for favorable survival after
metastasectomy.
• Nordlinger et al, 1996;
• Fong et al, 1999;
• Kattan et al, 2008;
• Rees et al, 2008

• In the series by Fong and colleagues (1999),
independent predictors of unfavorable prognosis:
1) the presence of extrahepatic disease,
2) a positive resection margin,
3) Node positive primary CRC,
4) a short disease-free interval(<1year)
5) largest liver metastasis greater than 5 cm,
6) more than one liver metastasis, and
7) serum CEA greater than 200 ng/mL.

• The presence of extrahepatic disease and a
postive resection margin are generally
determined intraoperatively.
• When presumed preoperatively, these two
variables are often considered relative
contraindications to metastasectomy.
• A preoperative clinical risk score (CRS) system
was therefore created using the last five factors
with each positive criterion counting as one
point.

• Total score out of 5 is highly predictive of outcome,
• with a score of 2 or less suggestive of a particularly
favorable prognosis—the optimal candidate for liver
metastasectomy.
• Patients with a CRS of 3 or 4 have less favorable
outcomes and may be appropriate for clinical trials
involving adjuvant chemotherapy.
• High CRS should not be considered a contraindication
to hepatic resection
» (Tomlinson et al, 2007).

Use of clinical risk score system
• It is validated by an independent group from
Norway (Mala et al, 2002),
• The CRS is generalizable to populations outside of
the index cohort from a single, large, tertiary
• In addition to appropriate patient selection for
surgery, the CRS has proven useful in selecting
patients for
– neoadjuvant treatment
– preoperative evaluation, ablation, and
– stratification in clinical trials.

• DL should be indicated in CRS>2, as risk of
occult extrahepatic disease is around 40%.
» Jarnagin et al 2001
• PET CT should be advised for CRS1 or more, as
chances of occult mets >14% in these patients
» Schussler fiorenza et al 2004

• Predictive models with added sophistication
have been developed recently, such as a
– nomogram (Kattan et al, 2008) and
– a multifactorial predictive index (Rees et al, 2008).
• These models are based on the same basic
prognostic factors as the earlier models
described above,
• They are more complex and difficult to use;

Pre op assesment
• 1) establishing the diagnosis and characterization
of primary.
• 2) anatomic definition of the liver lesion for
surgical planning,
• 3) staging to rule out extrahepatic disease.
• 4) general fitness for surgical resection.
– A confirmatory biopsy of hepatic lesions is only
indicated to confirm the diagnosis when the clinical
picture is unclear

Imaging
Should address the following five critical
issues:
1. Evaluation of liver metastases.
2. Possible hilar lymph node involvement.
3. Vascular invasion.
4. Liver volumetry.
5. Presence of extrahepatic disease.
(Valls et al. 2009).

• CT scan
• MRI abdomen
• USG  CEUS,
• PET CT
• IOUS

USG
• US is a rapid and non-invasive method
• operator dependent.
• Its sensitivity (50-70%)
• surpassed by other imaging studies.
» (Oldenburg & Albrecht 2008).

CEUS
• CEUS sensitivity and specificity in staging liver
metastases (80–95% and 84–98%,
respectively) approach those of CT and MRI.
• It is useful to improve the detection rate of
metastases smaller than 1 cm or of those
lesions that are isoechoic with respect to
adjacent liver parenchyma,
• (Oldenburg & Albrecht 2008).

CEUS
• Limited ability to observe certain parts of the
liver,
• Obese patients and/or in cases of steatosis and it
is not possible to simultaneously examine
multiple lesions in the arterial and early portal
phases.
• Hypervascular metastases and haemangiomas on
one hand and metastases and small cysts on the
other can be difficult to differentiate
» (Larsen 2010).

CT
• MDCT has a sensitivity of 70–85% and a
specificity of 90%, especially for lesions bigger
than 1.5–2 cm.
• Sensitivity is lower for small subglissonian
metastases, even though multi-slice CT allows
identification of hepatic lesions of 0.5 cm in
size
» (Guglielmi et al. 2005).

CT
• Hepatic volumetry, necessary to evaluate the
feasibility of major hepatectomies.
• In the case of atypical resections, CT software
able to highlight different liver segments and
to create vascular maps for arterial and portal
afferences, and for hepatic vein drainage
» Laghi et al 2005

MRI
• MDCT is usually preferred because it is more widely
available and because it is a well established technique
for surveying the extrahepatic abdominal organs and
tissues.
• characterization of focal lesions and
• is also preferred for patients who cannot receive
intravenous iodinated contrast material.
• when concerns about the risk of radiation from
repeated exposure to CT, as in children or young adults,
exists.
• In general, MRI sensitivity varies from 85-90% and its
specificity is up to 95%,

FDG PET
• FDG PET is a highly sensitive and specific
imaging study detecting hepatic metastases
from CRC (92–100% and 85–100%
respectively).
• With regard to the initial staging of patients
with metastatic CRC, FDG PET imaging leads to
a change in management in 2% to 36% of
patients.
» (Lucey et al. 2006).

• CT scanning remains a dominant imaging modality not only
for lesion detection and preoperative planning, but also for
treatment monitoring and post-treatment surveillance.
• FDG PET/CT may obviate the need for additional studies
and may improve patient management.
» (Bipat et al. 2007; Doan et al. 2010; Vauthey 2006).
• MRI has the highest sensitivity for lesion detection, but
because of its low sensitivity in detecting extrahepatic
disease in the peritoneum and chest, it is not a desirable
primary imaging modality
» (Vauthey 2006)
• Ultimately, the modality used must be tailored not only to
the patient and the clinical situation, but also to the
imaging expertise within the institution.

NCCN 2015
• (NCCN) guidelines do recommend that an FDG PET
scan be considered in the
– follow-up of a patient with CRC in the setting of CEA
elevation and suspected recurrence.
– also in the setting of a resectable synchronous or
metachronous liver metastasis.
• The utility of preoperative staging with FDG PET in
metastatic CRC is the focus of a currently accruing
randomized Phase III trial (PET START).
• Enrollment for this 400-patient study is nearing
completion, with results expected in the near future.

Diagnostic Laparoscopy
• As negative laparoscopy lengthens anesthetic
time and increases operating costs it should
be reserved
– Suspicious extrahepatic disease on imaging.
– CRS more than 2.
» Jarnagin and colleagues (2001),

IOUS
• IOUS has higher sensitivity of 98% and a
specificity of 95%, than transabdominal US,
MDCT and MRI.
• Allows identification of metastases 0.5 cm in size
and defining the relationship between lesion,
vessels and biliary structures.
• Modifying the planned surgical intervention in
18-30% of the patients.
• Hence it has become necessary tool, in addition
to palpation.
Starren ED Am Surg 1997

Japanese Society of Cancer of
the Colon and Rectum (JSCCR)
five conditions as criteria indicative for the resection of
CRLM:
(1) the patient is capable of tolerating surgery;
(2) the primary tumor has been controlled or can be
controlled;
(3) the metastatic liver tumor can be completely resected;
(4) there are no extra liver metastases or they can be
controlled; and
(5) the function of the remaining liver will be adequate.

Criteria of resectability
• There are at least three categories of patients
with CRLM:
• -First, the hepatic lesion(s) are clearly resectable
at the time of presentation.
• -Second, the hepatic lesion(s) are unresectable at
presentation but potentially convertible to
resection after primary CT called conversion CT.
• -Third, the hepatic lesion(s) are unresectable and
are unlikely to become resectable even with
effective CT.

Resectability
• No. of mets have not found to affect long
term survival of R0 resection achieved.
• Degree of response to chemotherapy is a
stronger predictor factor for long term survival
than the number of metastasis.
• Evidence shows that size is not a resectability
factor, but a factor related to tumour
aggressiveness
» (Altendorf-Hofmann et al. 2003)

Resectability
• Actual width of the surgical margin has no effect on
survival as long as the margin is microscopically
negative.
» (Figueras et al. 2007; Lordan 2007; Pawlik et al. 2005).
• A margin greater than 10mm is considered to be
optimum.
» (Casanova et al. 2004).
• Surgeons should to plan achive 10mm margin but, a
predicted margin of less than 1 cm should no longer be
considered an exclusion criterion for resection

Resectability
• Historically, extrahepatic disease has been
almost universally accepted as a contraindication
to liver resection.
• Recently, however, some series have shown a 5-
year survival rate of 12% to 37% after liver
resection in selected patients with extrahepatic
disease, independent of the location of that
disease (lung, primary colorectal recurrence,
retroperitoneal or hepatic pedicle lymph nodes,
peritoneal carcinomatosis, miscellaneous)
» (Elias et al. 2003, 2005).

Resectabilty
• Incidental peritoneal disease found at
laparotomy would contraindicate hepatic
resection.
• In general, resection in such patients should
only be considered after documentation of
stable/responsive disease with systemic
chemotherapy and when an R0 resection of
both intrahepatic and extrahepatic disease is
feasible.
» (Vauthey 2007).

• Positive hilar lymph nodes are associated with
a poor outcome and have been traditionally
considered as a contraindication to hepatic
resection of CRC liver disease.
• Recent papers shown long-term survival in
some patients with hilar nodal metastases,
(hepatoduodenal-retropancreatic area and
not in the common hepatic artery/celiac-axis
region)
» (Adam et al. 2008; Jaeck 2003).

• At present, the criteria for resectability include
any patient in whom all disease can be
– removed with a negative margin and
– who has adequate hepatic reserve.
• That is to say, instead of resectability being
defined by what is removed, now it is
sustained by what will remain after resection,
including patients with extrahepatic disease
» (Pawlik et al. 2008).

• There has been a shift in the concept of ‘resectability’ over
the past two decades.
• Traditionally unresectable disease if any of the following
criteria(EKEBERG’s ).
(i) more than four metastatic deposits;
(ii) Resection margin ,1 cm;
(iii) bilobar disease;
(iv) extrahepatic disease.
• Although these factors continue to convey a worse
prognosis, they are no longer regarded as an absolute
contraindication to liver resection, since a proportion of
these patients can undergo successful tumor clearance and
have long-term survival.

• American Hepato- Pancreato-Biliary Association
(AHPBA) consensus conference 2006
• Resectable
– when the disease can be completely resected,
– two adjacent liver segments can be spared with an
adequate vascular inflow and outflow and biliary
drainage,
– and the volume of the liver remaining after resection
(future liver remnant [FLR]) will be adequate
» (Vauthey 2006).

Approaches for resectable CRLM
• Resection (staged or synchronous) 
chemotherpay
• NACT  resection (staged or synchronous)
• Primary  chemotherapy  liver
• Liver  chemotherapy  primary.

Timing of resection
What are the possible options?
• Colon first: Staged approach
• Colon and liver: Simultaneous
approach
• “Reverse Strategy”

Factors determine the decision:
1. The presence of symptoms.
2. Location of primary tumor and
liver metastases.
3. Extent of tumor (both primary and
metastatic).
4. Patient performance status, and
underlying comorbidities.

Surgical incisions according to primary tumor
and liver metastases

Advantages of simultaneous resection
• a single surgical procedure.
• Reduced length of hospital stay
• The removal of all neoplastic foci and
interruption of the “metastatic cascade”.
• No delay in initiating systemic treatment

Disadvantages of simultaneous resections
• The combination of a “clean” and a
“contaminated” surgical procedure and thus
the higher risk of septic complications, which
could cause or worsen a liver dysfunction
• The increased risk of anastomotic leak due to
splanchnic congestion if prolonged pedicle
clamping is needed.

Disadvantages of simultaneous resections, cont.,
• The need for a double surgical team for liver
and colorectal surgery/inadequate treatment
if a single team performs the entire
procedure.
• The inadequate surgical exposure through a
single incision

Criteria for synchronous approach
– Age<70 years
– good surgical fitness.
– an adequate tumor-free margin,
– lesions that are not advanced(T4),
– less than 4 colorectal lymph node metastases
– histology that is not poorly differentiated or mucinous
adenocarcinoma.
– 3 or fewer liver metastases.
– a minor liver resection (less than 3 segments) is planned
Ann Acad Med Singapore 2010;39:719-33

“Reverse Strategy”
• Mentha et al. and the group from M.D. Anderson
Cancer Center reported it in 2006.
• Preoperative chemotherapy is followed by
resection of the hepatic metastases and then by
resection of the colorectal primary at a second
operation.
• The conclude treatment completion rate are
better in reverse approach but equall OS.
• J Am Coll Surg 2010;210:934-41.

The rationale for this approach
• It can be considered as an alternative option
in patients with advanced hepatic metastases
and an asymptomatic primary.
• Its can be better indicated to patient with
rectal tumor where pelvic surgical morbidity
may delay addressing liver mets.

• Only a minority of patients with liver metastases
is amenable directly to surgery (10-20%).
• Therefore, efforts have been made to increase
the resectability of patients with initially
unresectable colorectal liver metastases.
• Reasons of unresectability in liver limited CRLM.
– Inadequate FLR
– Bad anatomical location.
– Poor PS of patients.

Measures to increase resectability

• increase/preserve hepatic reserve,
- Portal Vein Embolisation: inadequate FLR
- Two- stage resection: bilobar disease
• combined local therapy: Resection Plus RFA
- Resect- larger lesion
- Ablate- smaller lesions
• decrease tumor size: Chemotherapy (near
major vessels.)
Ante-situ, in situ, and ex situ procedures :
extreme liver surgery.
ALLPS

Down staging chemotherapy
• Optimal regimen and sequencing remain matter of
debate.
• Some suggest low CRS should put on immediate surgery
if resectable and other should receive preop
chemotherpy.
» Fong et al 1999
• Using Chemotherapy for borderline resectable tumor is
standard method, but its role in resectable CRLM is a
matter of debate.
• Although there are no reports of outcomes of liver
resection after HAI, its complication rates are so high
(57%) that it is dismissed as a first option.

Chemotherapy
• Address micro mets
• Test tumor biology,
as aggressive tumor
may progress on
chemo and spare
unnecessary liver
resection.
• Make a borderline
resectable to
resectable one.
•Liver toxicity
steatohepatitis and
sinusoidal obs( blue liver)
 more morbidity and
mortality*
•Initailly resectable tumor
may progress over
chemotherpy.
•Certain lesions may
disappear on chemo.
(Nordlinger et al. 2008).

• NCCN recommends complete 6 months systemic
chemotherapy to address residual microscopic disease.
• systemic therapy can be given before, between, or after
resections, the total duration of perioperative
chemotherapy should not exceed 6 months.
• A 2012 meta-analysis of 3RCTS comparing S vs S & CT in
642 eligible patients (resectable CRLM)
• PFS and DFS better in CT arm (pooled HR, 0.75; CI, 0.62–
0.91; P = .003).
• But equal OS (pooled HR, 0.74; CI, 0.53–1.05; P = .088.)
» Ciliberto D, Prati U, Roveda L, et al. Role of systemicchemotherapy in the
management of resected or resectable colorectal liver metastases: a
systematic review and meta-analysis of randomized controlled trials.
Oncol Rep 2012;27:1849-1856. Available

• Found no difference in overall survival with the
addition of perioperative chemotherapy with
FOLFOX4 compared with surgery alone for
patients with resectable liver metastases from
colorectal cancer.
• However, the previously observed benefit in PFS
means that perioperative chemotherapy with
FOLFOX4 should remain the reference treatment
for this population of patients

• Peri-operative chemotherapy with FOLFOX4
improves PFS but does not statistically
significantly improve OS over surgery alone.

• The optimal sequencing of chemotherapy
remains unclear for resectable tumor
• Patients with resectable disease may undergo
liver resection first, followed by postoperative
adjuvant chemotherapy.
• Alternatively, perioperative (neoadjuvant plus
postoperative) chemotherapy can be used.
Araujo et al 2013.
Bilchik AJ et al 2008,
Adams et al 2009

Chemotherapy
• Novel chemotherapeutic regimens have been
associated with response rates (approximately
50%), allowing 10-30% of the patients with
initially unresectable disease to be successfully
treated with liver surgery
» (Adam et al. 2004).
• In addition, combination with biologic agents that
target angiogenesis and the epidermal growth
factor receptor (EGFR), bevacizumab and
cetuximab, achieves response rates of up to 70%,
increasing these figures
» (Vauthey 2006).

NCCN 1.2015
• FOLFOXIRI (infusional 5-FU, LV, oxaliplatin,
irinotecan) has been compared with FOLFIRI in 2
randomized clinical trials in patients with
unresectable disease, showed better resectability
rates, but more toxicity.
• Gruppo Oncologico Nord Ovest (GONO) 15 vs 6%
• Gastrointestinal Committee of the Hellenic Oncology
Research Group (HORG) trial 10 vs 4%
– FOLFIRI, FOLFOX, or CapeOx chemotherapy alone or
with bevacizumab;
– FOLFIRI or FOLFOX with panitumumab or cetuximab;
– FOLFOXIRI alone or with bevacizumab).

• Re-evaluation for resection should be done after
2 or 3 months of pre-operative chemotherapy
and every 2 months thereafter.
• Tumor progression before surgery is associated
with a poor outcome, even after potentially
curative hepatectomy.
• Tumor control before surgery is crucial to offer a
chance of prolonged remission in patients with
multiple metastases
» (Adam et al. 2004.)

• Patients should be referred early for
evaluation for resection.
• The peri-operative complication rate,
including hepatobiliary complications, is
higher with lengthy pre-operative
chemotherapy and is likely related to the
prolonged and sequential use of multiple
regimens
» (de Haas et al. 2011).

• Although resection has proven to be safe after
preoperative chemotherapy, the mortality rate
is increased in certain types of liver damage
associated with chemotherapy, specifically,
steatohepatitis associated with irinotecan
therapy.
» Vauthey et al 2006

Chemotherapy
• If bevacizumab is included as a component of
the conversion therapy, an interval of at least
6 weeks between the last dose of
bevacizumab and surgery should be applied,
with a 6- to 8- week postoperative period
before re-initiation of bevacizumab.

• Patients with disease converted to a resectable
state should undergo synchronized or staged
resection of colon and metastatic cancer as soon
as it become resectable.
• And patient should receive complete 6 months
treatment.
• In the case of liver metastases only, HAI therapy
with or without systemic 5-FU/LV (category 2B)
remains an option at centers with experience.

Disappearing mets
• 6-9 % develop radiological CR following NACT.
• Not all radiologically CR lesion shown PCR,
correlation ranging from 17-65% in various series.
• So concern will to find out these ghost lesions.
• Many variables are described correlating PCR.
– Lesion disappeared on HAI based Ct.
– Not visible on MRI
– CEA normalize.
» Benoist et al. 2006
» Elias et al 2008
» Auer et al 2010

• Patient with PCR showed better OS
» (thomay et al 2010)
• In general, all the original sites of disease
noted on the pre-therapy imaging need to be
resected or ablated.

Portal Vein Embolization
• To minimize risk of POLF, inadequate FLR and
IL hypertrophy of Liver parenchyma selective
embolization of Portal vein brach or ligation
done.
• It coz ipsilateral atrophy with FLR hypertrophy.
• Chemotherpy need not to modify except
bavacizumab.

• Chemotherapy does not seem to affect the
hypertrophy induced by PVE.
• A few studies using bevazucimab recommend a 6
week waiting period between the last dose and
the hepatectomy, although its influence on the
hypertrophy is unclear.
• Azoulay et al. reported that PVE increased the
feasibility of liver resection by 19% and that the
actuarial survival rate was 40% at 5 years, similar
to that of patients resected without PVE
» (Azoulay et al. 2000).

• There is a variety of substances used for
embolization, e.g. absolute alcohol, ethiodized
oil, cyanoacrylate with no clear difference
between them.
• PVE is well tolerated with minimum side
effects such as fever, nausea, and transient
abnormality of liver function test.

• Contraindications for PVE
– tumor invasion of the portal vein,
– portal vein thrombosis,
– Uncorrectable coagulopathy
– severe portal hypertension and
– renal failure

• Thus, the optimal time to evaluate the
hypertrophy after PvE is 3 to 4 weeks.
• Volumetric CT can be repeated at this time
because it provides two key pieces of
information:
– (1) if adequate liver volume has been reached;
– (2) growth rate, which is informative for the liver
capacity for regeneration

Two stage hepatectomy
• When planed resection not feasible in one stage
particularly in bilobar liver mets TSH should be
offered.
• It consists of combining two sequential and
planned liver resections, usually 4-6 week apart
(?)
• Frequently, it is associated with peri-operative
systemic chemotherapy and PVE, although it is
not a rule
» (Jaeck et al. 2004)

• In 2000, Adam et al.[63] proposed a new two-
stage approach for initially resectable liver
tumors.
• The maximum number of tumors removed in the
first operation, and a second surgery is
performed to remove the rest after a period of
liver regeneration.
• The goal of the double stage hepatectomy is to
minimize the risk of liver failure after massive
hepatectomy in patients with bilateral metastases

• Usually, on the first hepatectomy the FLR is cleared out of tumors
with non-anatomic resections and/or radiofrequency ablation or at
most a single segment resection.
• It can be associated to the removal of the primary colorectal tumor,
preferably through a laparoscopic approach or using a “J” incision if
it is located on the right colon.
• PVO can be done by PVE , 2-4 week after first stage
• Alternatively, PVE can be done during the first hepatectomy
through the ligation and alcoholization of the right portal vein
• The second hepatectomy can be done on the fourth of fifth week
after PVE, when an adequate hypertrophy of the non-embolized
hemi-liver is achieved.
Jaeck et al 2004
reverse approach

• Some authors recommend pre-operative
chemotherapy during the entire process. This
should be determined by the criteria of the
multidisciplinary team according to each
individual case
» (Adam et al. 2000).
• If during the second stage hepatectomy new liver
metastases or extrahepatic lesions are
discovered, such as localized peritoneum
implants, the procedure can still be performed if
a R0 resection can be achieved.(?)

• This procedure may be the only therapy able
to provide long-term survival and a possible
cure for patients with initially unresectable
multiple and bilobar CRC liver metastases.
• A recent series reports a 5 year overall survival
rate of 32% for patients on whom the
procedure had been completed
» (Narita et al. 2011).

Radiofrequency ablation
• Not all patients are suitable for liver resection for CRLM
and alternative therapies have been proposed.
• The most common alternative treatment for CRLM is
radiofrequency ablation (RFA).
• RFA involves placing an electrode into the liver tumor
under radiological guidance (ultrasound [U.S.], CT or
MRI),
• It generates thermal (radio frequency) energy which
destroys the tumor and a margin of normal
parenchyma.
• RFA can be performed percutaneously, laparoscopically
or during laparotomy.

• Larger follow-up data confirm the safety process,
but suggest that RFA may not be equivalent to a
local resection as a modality.
– Abdalla et al 2004
• Therefore, the long-term survival after resection
is better then after local ablation (65% vs 22%) [8]
• solitary CLM and showed that liver resection is
associated with greater survival rates 37% vs 5%

• The disadvantages of RFA include:
(1) High recurrence rate for large tumors (>5 cm);
(2) Necrosis of adjacent structures—major bile ducts,
stomach, duodenum, colon, and diaphragm;
(3) Delayed tumor recurrence on late (>3 years) follow
up higher than resection.
(4) Metastases must be clearly visible by imaging.(post
NACT)
(5) Not effective for surface tumor, near major vessels

• Currently, RFA is used primarily as an adjunct
to resection or as primary therapy when
resection is precluded regardless of cause.
• Neodymium-doped yttrium-aluminum-garnet
(Nd:YAG) laser and microwave are other
hyperthermic abalative methods.

Cryoablation
• Chemico physiologic sequelae of rapid freeze-
thaw cycles on cellular membranes to achieve
a total cell kill, tissue temperatures of˜ −50° C
or below are required.
• Depending on the size of the metastases, an
appropriate-sized cryoprobe is placed through
the metastases, and cryoablation is initiated
under ultrasonographic guidance

• Potential intraoperative complications of
hepatic cryosurgery include
– Accidental freezing of adjacent tissues,
– cracking of the liver parenchyma,
– bleeding due to the introduction of trotter probes,
– hypothermia and related cardiac arrhythmias,
– nitrogen embolism,
– bile duct or major vascular injury, and
– renal failure from myoglobinuria.

• Large vessels tolerate cryotherapy extremely
well without rupture or occlusion because of
the continued dissipation of thermal energy
by the flow of blood.
• In contrast, large bile ducts are extremely
vulnerable to cryoinjury, and caution should
be exercised in treating tumors located near
the hilum.

• Whether survival after cryoablation will be
equivalent to resection is yet undetermined.
• No randomized, controlled trials have been
performed to compare these treatments.
• Adjuvant cryoablation has been used
concurrently with resection for the treatment of
small, deep-seated hepatic metastases during
major hepatectomy, and consequently, has
extended the role of resection in some patients
who were otherwise unresectable.

Extreme liver surgery
• Total vascular occlusion. (IVC clamping and
pringle manuever).
• Useful when major vessels involved by tumor.
• Still investigational.
• Lesson learn from liver transplantation.
• In situ, ante situ, ex situ depending on level of
vascular detachment of liver

• The common basis for in-situ, ante-situ and
ex-situ resection is the total vascular exclusion
(TVE) of the liver, and the perfusion of the
organ by preservation hypothermic solution.
• Generally, a veno-venous bypass is used to
avoid venous congestion during prolonged
caval and portal crossclamping and a
hypothermic preservation solution is instilled
through the portal vein.

• Main indications of the three techniques are tumors that
involve vascular structures of the hilum, venous confluence
or inferior vena cava (IVC), or are in close proximity to
them.
• Ex-situ technique is losing support due to its high morbidity
and mortality.
• The location of the lesion or lesions in or near the
suprahepatic IVC represents a true challenge due to the
impossibility of using conventional resection techniques.
• Furthermore, optimal perioperative anaesthetic
management is crucial in this setting, and the anaesthesia
team should be familiar with the hepatic transplant
procedure.

• The involvement of the inferior vena cava does not
necessarily preclude resection.
• Liver resection with reconstruction of the IVC can be
performed in selected cases.
• The resected IVC may then be replaced with an autogenous
vein graft or a prosthetic material. The mortality rate of
resection IVC is 4.5-25% and morbidity up to 40%
» (Azoulay et al. 2005).
• The increased risk associated with the procedure appears
to be balanced by the possible benefits, particularly when
the lack of alternative approaches is considered
» (Hemming et al. 2004).

Re resection
• Most patients who undergo liver resection for
CLM have recurrence, and one third of these
recurrences develop only in the liver(MC).
• Selected patients with isolated hepatic
recurrence (30%) may undergo repeat
hepatectomy and achieve long-term survival.
Adam R et al 2003
Petrowky et al 2002 MSKCC

• After the third hepatectomy, survival rates at 5
years are estimated as 32% and postoperative
morbidity and mortality are not higher than after
the first hepatectomy.
• As bilobar multiple CLM recurrence are very likely
for recurrence, early diagnosis of the relapse is
important to maximize the number of patiets
appropriate for resection, and long-term survival
can be achieved with this approach.

(ALPPS)
• Associated liver partition and portal
vein ligation for staged hepatectomy.
• Recently, a new two-stage technique has been
developed with the acronym (ALPPS)
associating liver partitioning and portal vein
ligation for staged hepatectomy with the aim
of obtaining a more rapid and effective
increase in FLR, even though indications are
not clear yet.

Advantage
• Rapid and superior amount of FLR hypertrophy compared
with PVO alone.
• A short interval period, meaning early definitive liver
resection, unlikely tumor progression, and faster recovery
for the patient with early restart of chemotherapy;
• In cases of synchronic disease, for which combined surgical
procedures may require a greater functional hepatic
reserve, this new strategy enables the simultaneous
resection of the primary tumor and aggressive tumor
cleaning of the FLR;
• ALPPS might make curative resection possible even for
patients with a history of failed PVE or PVL.

• Despite the potential benefits of this novel approach,
there are some concerns.
• Probably the most important is the potential drawback
of manipulating a liver with a high tumor load and
leaving it for a week or more in a environment of
immunosuppression, inflammation, and stress, which
could cause spillage of tumor cells into the pulmonary
and systemic circulation.
• Whether or not this spillage does occur, and if so
whether it adversely affects the survival of patients
with CRLM, remains unknown

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