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Chapter20:Preoperative portal vein embolization
http://internalmedicinebook.com
insuciency.53 Chun etal. found the body weight method to
be equally as predictive as BSA54; however, a more recent study
1.0
comparing direct volumetric liver measurement and estimated
liver volume based on BSA found the TELV method to be superior (P<0.005).
55
Recent studies have expanded on alternative predictors of
postoperative liver function in addition to FLR. Indocyanine
green is a dye that binds to plasma proteins that is almost exclusively removed from the body by the liver via a carrier-mediated
mechanism.56 As such, indocyanine green retention at 15
minutes (ICGR15) serves as a surrogate quantitative meas-
0.8
0.6
Sensitivity
0.4
KGR
DH
sFLR
ure of liver function and has been validated in clinical series
to be helpful in prediction of postsurgical outcomes. ICGR15
is incorporated as a pivotal parameter in the seminal criteria
for safe liver resection proposed by Makuuchi etal. in 1993.57
0.2
In a retrospective analysis by Mihara etal., indocyanine green
plasma clearance rate (KICG) was incorporated with anticipated FRL volume (FRLV): (KICG×FRLV)/TLV to create a
new predictor of anticipated liver function (Krem) that correlated well with expected postoperative liver insuciency in a
series of 172 patients.
58
rough the analysis of a series of 107 patients who underwent right PVE and subsequent right hemihepatectomy or
extended right hepatectomy, Shindoh et al. proposed the
kinetic growth rate (dened as degree of hypertrophy at initial
volume assessment divided by number of weeks elapsed aer
PVE) as a predictor of postoperative complications aer hepatectomy as compared to the sFLR.59 e kinetic growth rate
0.0
0.0 0.2 0.4 0.6
Figure 20.3 Receiver operating characteristic curves for measured
volume parameters in the prediction of postoperative hepatic insufficiency.
Area under the curve (AUC) calculated for kinetic growth rate (KGR),
degree of hypertrophy (DH), and standardized future liver remnant (sFLR).
P-values represent asymptotic significance (null hypothesis, AUC = 0.500).
CI = confidence interval. (Modified with permission from Shindoh J, Truty
MJ, Aloia TA, et al. Kinetic growth rate after portal vein embolization predicts
posthepatectomy outcomes: toward zero liver-related mortality in patients
with colorectal liver metastases and small future liver remnant. J Am Coll Surg
2013; 216 (2): 201–209.59)
Best cut-off value
KGR 2.0% per week 0.830 (0.736-0.923) 0.048 0.002
DH 7.5% 0.727 (0.539-0.915) 0.096 0.03
sFLR 29.6% 0.665 (0.486-0.845) 0.096 0.12
1-Specificity
AUC (95% O) SE P
0.8
1.0
was found to be the most accurate predictor of postoperative
hepatic insuciency and mortality when compared to sFLR or
degree of hypertrophy measurements using receiver operating
characteristic analysis. Of the three measures, a kinetic growth
rate cuto value of < 2.0%/week demonstrated the highest
accuracy (81%), with sensitivity of 100% and specicity of 71%
in predicting postoperative hepatic insuciency (Figure20.3).
segment 3)is accessed, and the catheter is advanced into the
right portal venous system for embolization42 (Figure 20.4).
e major advantage of this approach is that catheterization
of the desired right portal vein branches is more direct via the
le system than via the right, making the procedure technically
easier. However, the disadvantage of this technique is the risk
of injury to the FLR parenchyma and the le portalvein.
Technical considerations forPVE
Standard approaches
PVE is performed to redirect portal blood ow toward the
hepatic segments that will remain aer surgery (i.e., the FLR). To
ensure adequate hypertrophy, embolization of portal branches
must be as complete as possible so that recanalization of the
occluded portal system is minimized. e entire portal system to
be resected must be occluded to avoid the development of intrahepatic portoportal collaterals that may limit regeneration.
60
PVE can be performed by any of three standard
approaches:the transhepatic contralateral (i.e., portal access
via the FLR), the transhepatic ipsilateral (i.e., portal access via
the liver to be resected), and the intraoperative transileocolic
venous approach. ese approaches are chosen based on operator preference, type of hepatic resection planned, extent of
embolization (e.g., right PVE [RPVE] with or without extension to segment 4)and type of embolic agentused.
In the transhepatic contralateral approach, developed by
Kinoshita etal.,20 a branch of the le portal system (usually
e transhepatic ipsilateral approach, rst described by
Nagino etal.61 in the mid-1990s (Figure20.5), is well accepted
in clinical practice with modications.
62,63
For this approach,
a peripheral portal vein branch in the liver to be resected is
accessed, through which the embolic material is administered. Because Nagino’s ipsilateral approach required the use
of specialized catheters, modications of the ipsilateral technique have been developed with standard angiographic catheters used for combined particulate and coil embolization
(Figure20.6).
62,63,64
When right hepatectomy is planned, RPVE
is performed (Figure20.7), and when extended right hepatectomy is planned, RPVE is extended to segment 4 (RPVE+4)
(Figure20.8). Ipsilateral RPVE±4 is performed aer a 5F or
6F sheath is placed into a distal right portal vein branch. When
RPVE+4 is needed, segment 4 embolization is performed rst
so as to not manipulate catheters through previously embolized segments. Amicrocatheter is advanced coaxially through
an angled catheter into the portal vein branches in segment 4
so that particulate embolics and coils can be delivered. Once
segment 4 embolization is completed, a reverse-curve catheter
is oen needed for RPVE. Aer complete occlusion of the right
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Section IV:Liver metastases
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necessitating the use of reverse-curved catheters. Another
potential disadvantage of this approach is that some embolic
material could be displaced upon catheter removal.
Kodama et al. compared complication rates between contralateral (n=11) and ipsilateral approaches (n=36) in a series
of 47 patients who underwent PVE.65 Contralateral-approach
PVE was associated with an 18.1% complication rate as compared to 13.9% for ipsilateral PVE. Although the dierence did
not reach statistical signicance, the authors recommended ipsilateral approach due to the potential for injury to the FLR during
contralateral approach. Di Stefano etal. reported on 188 patients
who underwent contralateral-approach PVE and found a 12.8%
adverse event rate and only one major complication (complete
Figure 20.4 Schematic representation of the contralateral approach. An
occlusion balloon catheter is placed from the left lobe into the right portal
branch, with delivery of the embolic agent in the antegrade direction.
portal vein thrombosis) directly related to the contralateral
approach that precluded surgery.66 Ribero etal. reported on 112
patients who underwent ipsilateral-approach PVE and found an
8.9% adverse-event rate.35 Accounting for the fact that Di Stefano
etal. included clinically occult CT ndings in their complications, the rates are comparable between the two studies.
e transileocolic venous approach is performed dur-
A
ing laparotomy by direct cannulation of the ileocolic vein and
advancement of a balloon catheter into the portal vein for
embolization.9 is approach is performed when an interventional radiology suite is not available, a percutaneous approach
is not considered feasible, or additional treatment is needed during the same surgical exploration.
67,68,69
Disadvantages of this
method are the need for general anesthesia and laparotomy, with
their inherent risks, and the inferior imaging equipment oen
(but not always) available in the operating room compared with
the state-of-the-art imaging equipment available in most interventional radiology suites. e transileocolic venous approach
B
has fallen out of favor in practice as improvements in experience,
imaging equipment, catheter systems, and embolic agents have
led to greater use of minimally invasive transhepatic approaches.
Additional approaches
In 2003, PVE using a transjugular approach was reported in a
series of 15 patients.69 is technique was attempted because
of the large experience gained during the previous decade with
Figure 20.5 Schematic representation of the ipsilateral approach for right
portal vein embolization and segment 4, as described by Nagino et al.12
Different portions of the balloon catheter are used for antegrade embolization
of segment 4 veins (A) and for retrograde delivery of the embolic agent into
the right portal system (B). (A modified from Vauthey JN, Abdalla EK, Doherty
DA, et al. Body surface area and body weight predict total liver volume in
Western adults. Liver Transplantation 2002; 8 (3): 233–24014; B modified from
Vauthey JN, Chaoui A, Do KA, et al. Standardized measurement of the future
liver remnant prior to extended liver resection: methodology and clinical
associations. Surgery 2000; 127 (5): 512–519,3 with permission.)
portal vein, embolization of the access tract is performed with
coils and/or Gelfoam to reduce the risk of perihepatic hemorrhage at the puncturesite.
One advantage of the ipsilateral approach is that the anticipated liver remnant is not instrumented. However, catheterization of the right portal vein branches may be more dicult
because of severe angulations between right portal branches,
transjugular intrahepatic portosystemic shunts. Under sonographic guidance, the right internal jugular vein was accessed,
and then with uoroscopy, a right or le portal branch was
punctured from a right, middle, or le hepatic vein. Acatheter was placed near the portal bifurcation and used to perform right portal branch embolization with a mixture of
n-butyl-2-cyanoacrylate (NBCA) and iodized oil. FLR hypertrophy was adequate, and right hepatectomy was performed in
12/15 patients with no PVE-related complications. For RPVE
in patients with cirrhosis, this may be an attractive approach;
however, the technical feasibility of RPVE extended to segment
4 using this approach and additional studies further validating
the technique have not yet been reported.
PVE in conjunction with transarterial therapies
Other approaches for PVE have been used. e idea of combining PVE and TAE for complete portal venous and hepatic
180
A B
http://internalmedicinebook.com
C
Chapter20:Preoperative portal vein embolization
Figure 20.6 Schematic representation shows modification of the ipsilateral technique for right portal vein embolization (RPVE) extended to segment
4. (A) Placement of a 6F vascular sheath into the right portal branch. An angled 5F catheter is placed into the left portal system with coaxial placement of a
microcatheter into a segment 4 branch. Particulate embolization is performed, followed by placement of coils, until all the branches are occluded. (B) After
segment 4 embolization is completely occluded, a 5F reverse-curve catheter is used for RPVE. (C) After PVE is complete, the access tract is embolized with coils
and/or Gelfoam to prevent subcapsular hemorrhage.
arterial occlusion has been described in patients with biliary
tract cancer and colorectal metastases who did not have sucient hypertrophy aer PVE alone.
70,71
e mechanism of TAE
is complementary, as a component of inammation and necrosis is added to the apoptosis-mediated cell death induced by
PVE to stimulate liver hypertrophy. In fact, arterial embolization alone has been shown to induce hypertrophy of the FLR,
though to a lesser degree compared toPVE.
72
Nagino etal. rst described the use of TAE to improve
FLR volume in 2 patients with cholangiocarcinoma who demonstrated inadequate hypertrophy following PVE.71 In both
patients, PVE in the setting of underlying liver disease led to
negligible hypertrophy of the FLR at 58days (patient 1)and
14 days (patient 2). Aer TAE, the FLR volume increased
from 470 to 685mL (46%) 2weeks aer TAE (patient 1)and
from 649 to 789mL (22%) 3weeks aer TAE (patient 2)and
both patients underwent successful curative resection. In this
study, only half of the target segments were treated due to
the potential risk of hepatic infarction given that both portal
and arterial systems were disrupted. Similarly, Gruttadauria
etal. reported inadequate hypertrophy aer PVE in 2 patients
with colorectal metastasis that demonstrated improved
hypertrophy aer TAE allowing for subsequent successful
hepatectomy.
70
TAE can also be performed as a staged procedure prior to
PVE, with an interval of 2–3weeks between the procedures to
help prevent hepatic infarction.
73,74
Aoki etal. reported the use
of sequential transcatheter arterial chemoembolization (TACE)
followed within 2weeks by PVE in 17 patients with HCC.73
Sixteen of the 17 patients were able to undergo staged hepatectomy with no episodes of postoperative hepatic insuciency.
Analysis of the explanted livers demonstrated profound tumor
necrosis without substantial injury to the non-cancerous liver,
and the authors encourage the use of this strategy in patients
with large HCC and chronically injured livers. In this patient
population, the rationale for performing TACE prior to PVE
includes prevention of tumor progression aer PVE, reduction
of arterioportal shunts that may limit the eectiveness of the
subsequent PVE, and boosting the regenerative stimulus in
chronically diseased livers.
Ogata etal. performed sequential TACE and PVE versus
PVE alone in a series of 36 patients with HCC and chronic liver
disease prior to right hepatectomy74 (Figure20.9). Patients in
the combined chemoembolization (TACE) and PVE group
(n=18) demonstrated a higher mean increase in percentage of
FLR volume (12% vs. 8%; P=0.022) than those who underwent
PVE alone (n=18). e incidence of complete tumor necrosis (83% vs. 6%; P < 0.001) and 5-year disease-free survival
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AB
C
D
Figure 20.7 A 59-year-old man with
colorectal liver metastases, status
post-oxaliplatin-based chemotherapy, who
had transhepatic ipsilateral right portal
vein embolization (RPVE) with particles
and coils prior to right hepatectomy.
(A) Contrast-enhanced computed
tomography (CT) scan of liver shows
small left liver (future liver remnant (FLR)/
total estimated liver volume (TELV) of
18% (arrows)). (B) Anteroposterior flush
portogram shows a 6F vascular sheath
(arrowheads) in a right portal vein branch
and a 5F flush catheter (arrow) in the main
portal vein. (C) A selective right portogram
is performed with 5F reverse-curve
catheter (arrow) prior to administration
of particles and coils. (D) Postprocedure
portogram shows occlusion of the portal
vein branches to segments 5–8 (white
arrows point to coils within the proximal
anterior and posterior-sector right
portal vein branches) with continued
patency of the veins supplying the
left lateral lobe (segments 2, 3, and 4).
(E) Contrast-enhanced CT scan of liver
performed 1 month after RPVE shows
hypertrophy of left liver (FLR/TELV of 32%
(arrows)). The patient underwent successful
right hepatectomy.
E
that catheter manipulation into branches feeding segment 4 is
rate (37% vs. 19%; P=0.041) was also signicantly higher in
patients who underwent TACE andPVE.
Extent of embolization
Prior to extended right hepatectomy, some authors have argued
for extending right PVE to include segment 4 (RPVE+4) as
a means of improving hypertrophy of segments 2 and 3.71 In
addition, RPVE only in the setting of extended right hepatectomy results in undesired segment 4 hypertrophy, which
results in a larger area of intraoperative parenchymal transection across the hypertrophic segment.12 A second potential
benet of RPVE+4, from an oncological standpoint, is that
the entire tumor-bearing liver is systematically embolized to
reduce the risk of tumor growth that may result from increased
portal blood ow and hepatotrophic factors. e drawback is
more technically demanding and inadvertent reux of embolic
material to the FLR has been reported.
75,76
Capussotti et al. evaluated 26 patients who underwent
RPVE (n=13) or RPVE+4 (n=13) and found no dierence
in the volume increase (P=0.20) or rate of increase (P=0.40)
of segments 2 and 3 in the two groups.75 However, recent studies comparing RPVE and RPVE+ 4 have reported improved
hypertrophy of segments 2 and 3 when segment 4 is also embolized without increased incidence of complications.
35,77,78
Kishi
etal. compared patients who underwent RPVE (n=15) versus those that underwent RPVE+4 (n = 58).77 Compared to
RPVE alone, the RPVE+4 group demonstrated a greater absolute increase in segment 2/segment 3 volume (median, 106 vs.
141mL; P=0.044) as well as a higher hypertrophy rate for segments 2+3 (median, 26% vs. 54%; P=0.021). e complication
182
Chapter20:Preoperative portal vein embolization
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A
B C
DE F
Figure 20.8 Transhepatic ipsilateral right portal vein embolization (PVE) extended to segment 4 using tris-acryl particles and coils performed in a 48-year-old
female with cholangiocarcinoma involving segments 4, 5, and 7. (A) Contrast-enhanced computed tomography (CT) image of the liver with a lesion centered
in segment 7 and the normal-appearing left lateral liver prior to PVE. (B) CT obtained after PVE demonstrates hypertrophy of the future liver remnant (FLR)
(standardized FLR growth 27–35%, kinetic growth rate 4%). (C) Anteroposterior flush portogram obtained through a 5F flush catheter within the main portal vein
via ipsilateral approach demonstrates patent conventional portal anatomy. (D) Intraprocedural fluoroscopic image from PVE depicts coil placement into segment 4
branches via a microcatheter. (E) Final portogram shows occlusion of the portal vein branches to segments 4–8 with continued patency of the veins supplying the
left lateral liver (arrows). (F) CT image obtained after uncomplicated extended right hepatectomy shows massive hypertrophy of the remnant liver.
rates were similar for RPVE and RPVE+4 groups (7% vs. 10%;
P>0.99) and no PVE complication precluded resection.
Embolic materials
A variety of materials and devices exist for embolization
and some of these have been adapted for the portal system.
Commonly reported agents include polyvinyl alcohol, Gelfoam,
brin glue, NBCA, polidocanol foam, microspheres, Lipiodol,
coils, and Amplatzer plugs, among others.
79,80
An ideal material will provide permanent portal venous embolization that is
safe and well tolerated by the patient.15 e two agents most
commonly discussed currently are NBCA and microspheres in
combination with coils. To date, there has been no prospective,
randomized trial comparing thetwo.
NBCA has been shown to produce portal venous occlusion for more than 4 weeks81 and has been shown to induce
a larger FLR when compared with coils and gelatin sponge.42
NBCA induces an inammatory reaction, resulting in peribilliary brosis,42 and rates of liver regeneration are believed to
be as good as or better than other embolic agents. However,
preparation and administration require advanced knowledge
and experience and the inammatory reaction sometimes renders surgical resection more dicult.42 Non-target embolization has been reported and a technique has been developed to
prevent backow by placing a nitinol plug.82 NBCA is mixed
at a ratio of 1:4–5 with ethiodized oil and is delivered through
an end-hole angiographic catheter from second- or third-order
portal branches to prevent non-target embolization. Straight
catheters are preferred by some operators to prevent gluing of
catheters into the liver and great care must be taken to prevent
embolization of NBCA to non-targetareas.
Multiple studies have demonstrated the safety and eectiveness of small-particle embolization of the liver with both
polyvinyl alcohol particles and microspheres.
62,83
Aer catheterization of the portal system, embolization of distal small
veins is performed with 100–300-m particles. More proximal veins are embolized with larger particles with a goal of
near-stasis of ow or stasis. Coils are placed behind particles to
prevent later particle dislodgment and recanalization, improving hypertrophy of the FLR. Arecent study by Geisel etal. demonstrated superior FLR hypertrophy with reported percentage
volume gain of 53.3± 34.5% with the use of coils and plugs in
combination with particles versus 30.9±28.8% with the use of
particles alone (P=0.002).
84
Complications
In 2010, the Society of Interventional Radiology established
quality improvement guidelines for TAE, including a suggested
threshold for PVE-related major complications of 6% and morbidity of 11%.85 Most published complication rates fall well
below this range.86 Abulkhir etal. published a meta-analysis
of 1,088 subjects pooled from 37 studies from 1990 to 2005
who underwent PVE and found the pooled procedure-related
morbidity and mortality to be 2.2% and 0%, respectively.87
In their analysis, percutaneous PVE was performed in the
majority of cases (72%); the remainder were performed via
the transilecolic technique. Complications of PVE are similar
to other image-guided transhepatic procedures and include
183
Section IV:Liver metastases
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AB
C
D
Figure 20.9 A 74-year-old man
with an 8-cm solitary hepatocellular
tumor and hepatitis C cirrhosis who
underwent sequential transcatheter
arterial chemoembolization (TACE)
followed 1 month later by right portal
vein embolization (RPVE) prior to a right
hepatectomy. (A) A single image from
pre-PVE contrast-enhanced computed
tomography (CT) scan shows small left
liver (arrows) and (future liver remnant
(FLR)/total estimated liver volume
(TELV) of 27%. (B) A single image caudal
of (A) shows the solitary 8-cm tumor
(arrows). (C) Pre-embolization portogram
(after TACE) shows persistent iodized oil
uptake within the right lobe (arrows).
(D) Postembolization portogram shows
complete occlusion of all branches to right
portal vein. The left portal vein remains
patent. (E) A single image from post-PVE
contrast-enhanced CT scan shows
hypertrophy of the left liver (arrows). The
FLR/TELV increased to 47%. (F) A single
image from post-PVE contrast-enhanced
CT scan more caudal to (E) shows massive
atrophy of the right lobe with necrosis of
the tumor (arrows). The patient underwent
uncomplicated right hepatectomy. No
viable tumor cells were found in the
resected specimen.
EF
subscapular hematoma, hemoperitoneum, hemobilia, abscess
formation, cholangitis and sepsis, arterioportal shunts, arterioportal stula, and pneumothorax. In addition, PVE-specic
complications include non-target embolization, recanalization
of embolized segments, and extension of portal vein thrombosis to involve the le or main branches.
liver resection (e.g., hepatectomy plus pancreaticoduodenectomy) must be considered. ese three factors are considered
in the setting of the patient’s age and comorbidities (e.g., diabetes) that may aect hypertrophy. us, once the procedure
type and extent of resection necessary to treat the patient have
been determined, appropriate liver volumetry is performed so
that the standardized FLR volume expressed as a percentage of
Indications and outcomes forPVE
General indications
To determine whether a patient will benet from PVE, several
factors must be considered.15 First, the presence or absence of
underlying liver disease will have a major impact on the volume of liver remnant needed for adequate function. Second,
patient size must be considered; larger patients require larger
liver remnants than do smaller patients. ird, the extent and
complexity of the planned resection and the possibility that
associated non-hepatic surgery will be performed at the time of
the estimated TLV can be used to determine the need forPVE.
As described earlier, a normal liver has a greater regenerative capacity than a cirrhotic liver, functions more eciently,
and tolerates injury better. Patients can survive resection of
up to 90% of the liver in the absence of underlying liver disease, but survival aer resection beyond 60% of the functional
parenchyma in patients with cirrhosis is unlikely.5 Lethal
postresection liver failure is more common aer resection in
patients with cirrhosis, and other complications of the poorly
functioning liver remnant (e.g., ascites, uid retention, and
wound breakdown from poor protein synthesis) occur more
oen aer resection in patients with cirrhosis than in patients
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Chapter20:Preoperative portal vein embolization
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without cirrhosis. With regard to liver volume, there is a limit
to how small a liver can remain aer resection. If too little liver
remains aer resection, immediate postresection hepatic fail-
25
No hepatic dysfunction
Hepatic dysfunction
ure leads to multisystem organ failure and death. If a marginal
volume of liver remains, cirrhotic or not, the lack of reserve
20
oen leads to a cascade of complications, prolonged hospital and intensive care unit stays, and slow recovery or slowly
progressive liver failure over weeks to months, with eventual
1,2,3
death.
General contraindications
15
PVE is an adjunctive procedure to major hepatectomy. Hence,
contraindications to PVE mirror those of hepatectomy. Severe
portal hypertension precluding surgery is the only absolute
contraindication to PVE. Also, in cases where tumor obstructs
the portal system in the liver to be resected, PVE is not necessary as portal ow is already redirected to the FLR.
64,88
Relative
contraindications include uncorrectable coagulopathy, renal
10
Hypertrophy Rate (%)
5
failure, and extrahepatic metastasis. Two-stage hepatectomy
has expanded the patients with bilobar hepatic disease burden
eligible for PVE and potential curative resection; however, diffuse hepatic disease burden remains a contraindication toPVE.
Normal underlyingliver
In patients with an otherwise normal liver, the indications for
PVE have evolved with the greater accuracy of liver volumetric measurements and the use of standardized liver volumes.
Although extended resections can be performed with a low
0
sFLR ≤20% sFLR >20%
Figure 20.10 Presence of hepatic dysfunction by standardized future liver
remnant (sFLR) volume and degree of hypertrophy. (Used with permission
from Ribero D, Abdalla EK, Madoff DC, Donadon M, Loyer EM, Vauthey
JN. Portal vein embolization before major hepatectomy and its effects on
regeneration, resectability and outcome. Br J Surg 2007; 94 (11): 1386–1394.35)
likelihood of death from liver failure, small-for-patient-size
normal liver remnants are associated with increased complications and slower postoperative recovery.3 An FLR/TELV of
less than 20% is associated with a fourfold increase in complications compared with an FLR/TELV of 20% or more.5 is
nding was validated in a retrospective study that revealed that
residual liver volume, not resected volume, predicts posthepatectomy course.
4
It is also important to recognize and individualize the indication for PVE with use of the standardized 20% cuto for liver
volume due to intrahepatic segmental variability. Liver volume
analysis revealed that the lateral le liver (segments 2/3) contributes less than 20% of the TLV in more than 75% of patients
in the absence of compensatory hypertrophy. In addition, the
le liver (segments 2/3/4) contributes 20% or less of the TLV
in more than 10% of patients.89 erefore, an FLR/TELV of less
than 20% can be expected in most patients who do not develop
compensatory hypertrophy from tumor growth and require an
extended right hepatectomy. In these patients, RPVE extended
to segment 4 is indicated. However, le PVE is rarely needed;
Nagino etal.12 showed that an extended le hepatectomy with
caudate lobectomy results in resection of only 67% of the liver,
leaving an FLR of 33%, the same residual volume aer right
hepatectomy in a normal liver. Volumetric analysis of normal
livers also conrms the consistently large volume of the posterior right liver (segments 6/7).
90
e outcome from PVE and subsequent resection may
be even more closely linked to the PVE technique in patients
with otherwise normal livers than in patients with chronically
diseased livers. In patients with cirrhosis, RPVE (without segment 4)is the most common technique used, since extended
hepatectomy is rarely indicated or possible. In patients without
cirrhosis who have hilar biliary duct cancer, liver metastases, or
HCC,91 extended hepatectomy resection of the right liver + segment 4±1 (extended right hepatectomy) or, less oen, the le
liver + segments 5 + 8±1 (extended le hepatectomy) is oen
indicated. In the former case (i.e., extended right hepatectomy),
owing to the consistently small volume of the le lateral bisegment (2+3), preoperative PVE is frequently needed.
89
Multiple studies have demonstrated that hepatectomy in a
setting of sFLR < 20% is associated with increased postoperative
complications.
5,35,92
Ribero etal. found that both standardized
FLR <20% and degree of sFLR hypertrophy aer PVE <5%
predicted outcome aer resection in a series of 112 patients
(Figure20.10).35 Kishi etal. published a series of 301 consecutive patients who underwent extended right hepatectomy and
found that patients with a preoperative sFLR <20% had signicantly higher rates of postoperative liver insuciency and
death from liver failure compared with patients with sFLR
>20% (P<0.05).92 In addition, patients who underwent PVE
before surgery to increase their standardized FLR from <20%
to >20% had statistically equivalent rates of liver insuciency
as patients with >20% at baseline (Figure20.11). is study
conrmed both the sFLR threshold of <20% associated with
increased perioperative complications and the benecial role
of PVE in reducing perioperative complication rates in those
patients with hypertrophy of the liver to an sFLR>20%.
185
Section IV:Liver metastases
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A
50%
40%
30%
20%
10%
Hepatic InsufficiencyDeath from Liver Failure
0%
B
20%
15%
10%
5%
0%
Underlying liver disease
Major resection can be performed safely in some patients with
13/38
(34%)
≤ 20 > 20 - 30
4/38
(11%)
≤ 20 > 20 - 30
P < 0.001
P < 0.038
cirrhosis, although extended hepatectomy is rarely an option.
Unlike patients with normal liver, those with cirrhosis with marginal liver remnants are not only at risk for complications but
are also at increased risk for death from liver failure.2 However,
in carefully selected patients with cirrhosis with preserved liver
function (Child–Pugh class A) and normal ICGR15 (< 10%),
major resection can be performed safely and PVE is indicated
when the sFLR volume is less than 40% of the TLV.8 is guideline is supported by the nding that sFLR volume predicts death
from liver failure aer hepatectomy in chronic liver disease.
ese studies are corroborated by Farges etal.,93 who showed
that patients with chronic liver disease who underwent PVE
before right hepatectomy had fewer complications and shorter
intensive care unit and hospital stays than those with chronic
liver disease who did not have PVE before right hepatectomy.
is guideline has been expanded to include patients in whom
the liver is compromised by prolonged biliary obstruction who
require extended hepatectomy.
3,6,9,32,48
Highly selected patients with advanced liver disease might
also undergo safe resection. Specically, in patients with cirrhosis with a moderately abnormal ICGR15 (10–20%) but with
preserved liver function, sequential TACE and PVE have been
used to maximize the atrophy–hypertrophy complex.73 Because
of the continuum of “liver disease,” the specic indications for
PVE in patients with chronic liver disease remain to be dened
precisely and require an individualized approach. It is anticipated that rened criteria will be developed with the accrual of
more experience with the standardized measurement ofFLR.
In patients with chronic liver disease such as chronic hepatitis, brosis, or cirrhosis, the increase in non-embolized liver
volumes aer PVE varies (range, 28–46%), and hypertrophy
aer PVE may take more than 4 weeks because of slower
P = 0.010
15/144
(10%)
sFLR (%)
P = 0.021
4/144
(3%)
sFLR (%)
P = 0.293
P = 0.633
2
16/108
(15%)
> 30
2/108
(2%)
> 30
regeneration rates.
32,41
thought to limit regeneration, possibly as a result of reduced
portal blood ow.94 e complication rates aer PVE are higher
in patients with chronic liver disease than in those with an
otherwise normal liver because of the increased risk of secondary portal vein thrombosis, presumably from slow ow in
the portal vein trunk aer PVE.
of the tumor followed by PVE within 2weeks may optimize
outcome for some patients who have HCC in the presence of
chronic liver disease and require major resection.
In patients with chronic liver disease, hepatectomy outcomes,
including the number and severity of complications and the incidence of postoperative liver failure and death, are better with
PVE than without.
25,41,44,93,95,96
long-term outcomes aer resection of three or more liver segments for HCC in patients with cirrhosis. PVE was performed
when the FLR volume was predicted to be less than 40% and led to
signicant increases in the FLR volumes in all embolized patients.
Importantly, none of 10 patients who underwent PVE had liver
failure or death following resection, whereas three of 19 patients
in the non-PVE group suered liver failure and one patient
died. Overall and disease-free survival rates were similar with or
without PVE. Tanaka etal.96 reported several benets of PVE in
a larger study of patients with HCC and cirrhosis. Disease-free
survival rates were similar, but cumulative survival rates were signicantly higher in the PVE group than in the non-PVE group. In
addition, patients with recurrence following PVE plus resection
were more oen candidates for further treatments such as TACE,
an additional benet of PVE in the longterm.
High-dose chemotherapy
Accelerated tumor growth aer PVE has been reported for
both primary and metastatic liver tumors.
of disease aer PVE may preclude curative intent surgery; a
Figure 20.11 Rates of (A) hepatic
insufficiency and (B) death by preoperative
standardized future liver remnant (sFLR)
volume. (Modified with permission
from Kishi Y, Abdalla EK, Chun YS, et al.
Three hundred and one consecutive
extended right hepatectomies: evaluation
of outcome based on systematic
liver volumetry. Ann Surg 2009; 250
(4): 540–548.92)
e degree of parenchymal brosis is
66,94
e combination of TACE
73
In 2000, Azoulay etal.95 reported
97,98,99,100
Progression
186
Chapter20:Preoperative portal vein embolization
http://internalmedicinebook.com
A
Percent
30
25
20
15
10
Figure 20.12 Postoperative liver insufficiency (PHI) and mortality from liver failure in patients who underwent extended right hepatectomy in the setting of
colorectal metastases, stratified to those undergoing no chemotherapy, chemotherapy, or long-duration (>12 weeks) chemotherapy. (A) Standardized future liver
remnant (sFLR) > 20% cutoff; (B) sFLR > 30% cutoffs for resection eligibility. (Used with permission from Shindoh et al.
5
PHI
Death from
liver failure
0/30 (0.0%)
No
chemo
P = 0.49
4/78 (5.1%)
1/78 (1.3%)
P = 0.006*
Chemo
≤ 12 weeks
14/86 (16.3%)
2/86 (2.3%)
Chemo
> 12 weeks
20% dropout rate aer rst-stage resection due to progression
of disease has already been reported in two-stage hepatectomy
101,102
series.
Neoadjuvant chemotherapy can be administered in
an attempt to provide tumor control in the interim between
PVE and resection; however, concerns have been raised about
its potential deleterious eect on liver function, liver hypertrophy, and lack of ecacy in preventing progression of disease.
Two separate series, one by Pawlik et al. and another by
Vauthey etal., have demonstrated an association of oxaliplatin
with sinusoidal dilation and irinotecan with steatohepatitis.
103,104
In the series by Vauthey etal., the presence of steatohepatitis
in patients who had undergone resection was correlated to
increased 90-day mortality (14.7% vs. 1.6%; P= 0.001; odds
ratio (OR)=10.5; 95% condence interval, 2.0–36.4). Given
these ndings, Shindoh etal. performed a retrospective analysis on a series of 194 patients with colorectal liver metastasis to
determine the optimal FLR for patients treated with neoadjuvant chemotherapy.
105
e authors found that both long duration of chemotherapy (dened as >12weeks) and sFLR ≤30%
were predictors of hepatic insuciency (OR=5.4, P=0.004;
B
Percent
30
25
20
15
10
5
PHI
Death from
liver failure
P = 0.1
0/5 (0.0%) 0/26 (0.0%)
No
chemo
Chemo
≤ 12 weeks
105
)
P = 0.15
2/20 (10.0%)
Chemo
> 12 weeks
compared to the no-chemotherapy group at 4weeks aer PVE.
Similarly, Covey etal. also reported on patients with colorectal
liver metastases who underwent PVE either with (n=47) or
without (n=53) neoadjuvant chemotherapy, with no signicant
dierence in median contralateral liver growth aer PVE.
Several studies have examined the eect of chemotherapy
on disease progression aer PVE prior to hepatectomy.
Fischer etal. reported on a series of 64 consecutive patients
who underwent PVE stratied into two groups: those who
received chemotherapy (n = 25) and those who did not
(n=39), in anticipation of extended right hepatic resection.
ere was no statistical dierence between the proportion of
patients who ultimately underwent hepatic resection between
two groups; the chemotherapy group had statistically lower
rate of progression by Response Evaluation Criteria In Solid
Tumors (RECIST) criteria (18.9% vs. 34.2%; P = 0.03). Of
greater importance, the chemotherapy group demonstrated
a clear survival benet as compared to the no-chemotherapy
group (49% vs. 24% 5-year survival; P=0.006) in both the surgical resection and non-surgical cohorts.
107
108,109
109
OR 6.3, P=0.019, respectively) (Figure20.12). No cases of post-
operative mortality and only 2 cases of postoperative hepatic
insuciency were reported if the sFLR >30%; indicating that a
sFLR >30% may be a more appropriate cuto value in patients
who have received neoadjuvant chemotherapy, particular if the
duration of treatment is >12weeks.
In addition, the eect of systemic neoadjuvant chemotherapy on liver hypertrophy aer PVE has been addressed by several studies. Zorzi etal. reviewed FLR hypertrophy aer PVE in
patients with colorectal liver metastases who underwent PVE
either with concomitant neoadjuvant chemotherapy (n= 43)
or without chemotherapy (n =22) prior to resection.
106
e
chemotherapy group, which included 26 patients treated in part
with the vascular endothelial growth factor receptor blocker
bevacizumab, demonstrated similar rates of hypertrophy when
Conclusion
PVE is a validated technique to increase the volume and function of the remnant liver prior to resection of hepatobiliary
cancer. PVE reduces perioperative morbidity and allows for
safe, potentially curative hepatectomy in patients previously
considered ineligible for resection based on anticipated small
remnant livers. e use of a reproducible, accurate index of
posthepatectomy liver function, such as the sFLR, is essential
for PVE. In addition, careful attention to key factors, such as
the presence or absence of underlying liver disease, the use of
chemotherapy, and the surgical approach, permits the appropriate selection of patients for PVE. Currently recommended
thresholds prompting consideration of preoperative PVE are
187
Section IV:Liver metastases
http://internalmedicinebook.com
sFLR of ≤20% for patients with an otherwise normal liver, 30%
or less for patients who have received chemotherapy, especially
for durations greater than 12weeks, and <40% for patients with
chronic liver disease. PVE continues to demonstrate an essential adjunctive role to major hepatectomy, even as advances in
hepatobiliary surgical techniques evolve and indications for
curative hepatectomy expand, given its high safety prole and
proven ecacy at promoting liver remnant hypertrophy.
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