Department of HPB Surgery and Surgical Oncology, Methodist Dallas Medical Center, Dallas, Texas
*Corresponding author:
Dr. D. Rohan Jeyarajah, MD FACS
Director Surgical
Oncology/ HPB fellowship
Methodist Dallas Medical Center
221 West Colorado
Blvd, Suite 100, Dallas, TX 75208 E-mail: rjeyar@sadtx.com
Received April 26, 2011; Accepted May 26, 2011; Published June 15, 2011
Citation: Lowe K, Jeyarajah DR (2011) Integration of Surgery and
Radioembolization in Treatment of Hepatic Tumors. J Nucl Med Radiat Ther 2:105.
doi:10.4172/2155-9619.1000105
The treatment of liver malignancies has evolved over recent decades.
Historically, patients with liver tumors were considered incurable. With
the advent of safer surgery and adjuncts such as radiospheres, patients
can now enjoy long term survival and even cure in the face of liver
tumors. Liver malignancies can either originate from the liver itself,
such as hepatocellular carcinoma (HCC), or can metastasize to the liver
from other sites; colorectal cancer liver metastasis (CRLM) being the
most common example. There are many options for patients with liver
tumors. Surgical resection remains the gold standard but ultimately can
only be offered to 20% of patients with CRLM [1], most often because
a functional liver remnant adequate to sustain life would not remain.
This series of articles will cover the many options that are available
to patients with liver tumors. Our aim here is to review the current
literature concerning the multimodiality treatment of primary and
metastatic liver tumors and to provide a surgical perspective regarding
the rational use of non-resective therapy. Herein we will focus on
the most common tumors of the liver: hepatocellular carcinoma
(HCC), colorectal liver metastasis (CRLMs) and liver metastases from
neuroendocrine tumors (NLMs). Other articles in this series will cover
additional non - surgical treatment modalities which are available
for patients with liver tumors. It is important to understand that only
surgical resection offers a chance for a cure of primary liver tumors
and liver only metastases. For this reason and because recent advances
in multimodality treatment have increased the number of borderline
resectable patients who ultimately undergo R0 resection, we advocate
that surgical evaluation be included in the multidisciplinary work up
of patients with liver tumors. For reasons discussed below, we believe
that surgical evaluation is important even for those who may seem to
be poor candidates for surgery due to multiple or very large tumors.
Hepatocellular carcinoma
Hepatocellular carcinoma (HCC) is the fourth leading cause of
cancer-related deaths in the world, with most HCC occurring in the
setting of cirrhosis and infection the hepatitis B or C viruses in the
West. Largely due to a maturing population of Americans infected with
hepatitis C, the age adjusted American incidence of HCC has increased
significantly in the last twenty years. In Asia, and Africa, infection by
the hepatitis B virus is the leading risk factor. An increased risk for the
development of HCC are those with hepatitis B carrier state, chronic
hepatitis C infection, hereditary hemochromatosis, cirrhosis of any
etiology and some environmental exposures[2-5].
Diagnosis of HCC
The diagnosis of HCC is made on the basis of clinical and social
history, radiologic appearance, serum alfa-fetal protein (AFP) level
and biopsy. Infection with hepatis viruses carries significant risk of
development of HCC in the setting of cirrhosis. In a recent study, North
Americans with HCC were infected with hepatitis B virus (HBV) or
hepatitis C cirus (HCV) 16% and 36 % of the time, respectively [6]. In
the Far East, the vast majority of patients with HCC are also infected
with one of the hepatitis viruses [6]. While the majority of patients diagnosed with HCC and HCV infection will have cirrhosis [7], it is
significantly less common to find cirrhosis in those who develop HCC
in the context of hepatitis B infection [8]. Importantly, this is the more
common background in which HCC develops in the Far East. While
the majority of HCC develop in cirrhotics in the West this is not the
case in the far east where the majority of HCC develops in patients
with hepatitis B infection but no cirrhosis [3,6]. This may mean that
patients with HCC in the Far East are more often candidate for surgical
resection due to the absence of cirrhosis and decreased risk of post
operative liver failure, an important point when comparing results of
studies conducted in these populations.
The high incidence of HCC in cirrhotic has led to recommendations
for surveillance of those with known cirrhosis, including ultrasound +/-
serum AFP measurement every 3 to 12 months [9-12]. Management
of masses found in cirrhotics incidentally or via surveillance can be
stratified according to size and appearance in imaging. A solid sub cm
lesion which does not enhance on contrast imaging is unlikely to be
HCC, and can be followed with repeated imaging every 3 to 6 months
to verify absence of growth [13,14]. On the other hand, a 1-2 cm lesion
which arises in a cirrhotic liver is more likely to be HCC. These smaller
lesions are less likely to have the typical features of larger HCC lesion on
imaging. For this reason percutaneous biopsy may remain a diagnostic
tool in this group of patients [9,15]. Lesions greater than 2 cm, which
have a typical appearance on contrast imaging, found in a cirrhotic liver,
and in a patient with elevated serum AFP are very likely to be HCC and
can be treated as such without biopsy[16] (Figure 1). Biopsy has been
associated with needle track seeding in 2-3 % of punctures [15,17], and
the risk of bleeding in 0.5 % [18,19]. Current guidelines suggest that
typical appearance on two contrasted imaging modalities and a solid
lesion greater than 2 cm in diameter has a positive predictive value of
95 % regardless of AFP level, while any enhancing mass on imaging and
an AFP of 200 is diagnostic[9,16,20]. Others believe that only an AFP
value of 500has sufficient sensitivity [21]. It is important to note that up
to 40% of HCCs will not produce AFP, and therefore a negative result
does not exclude the diagnosis [10].
Figure 1: Lowe, Jeyarajah.
Staging of HCC
Staging of HCC can be done according to the tumor-node metastasis
(TNM) system [22], or the united organ sharing system
(UNOS). Both of these systems, however, do not include the extent of underlying liver disease which has important implications for survival
and surgical management [23]. Surgical planning is often aided by
scoring systems such as the Child-Pugh classification which scores liver
failure according to the presence of encephalopathy and ascites and the
values of INR, albumin and bilirubin [24], or by the model for end stage
liver disease (MELD) which is calculated based on creatinine, INR, and
total bilirubin [25]. However, neither of these systems addresses the
degree of tumor burden or extent of required resection. Other systems
have been developed to have prognostic value which includes both
tumor burden and underlying liver function [26-28], however these
systems may not have prognostic value in non-surgical patients, and
do not stratify patients sufficiently to guide treatment [29,30]. The
Barcelona Clinic Liver Cancer (BCLC) staging system has had more
prognostic value and links tumor stage to treatment strategy [31-34].
Indications for resection of HCC
Surgical removal of HCC offers the only hope for cure, but resection
should only be undertaken in patients where there is an expectation
of margin-negative (R0) resection and who will have adequate liver
function perioperatively [33]. Advances in operative technique and
perioperative care have greatly decreased the historical 30 % mortality
associated of major hepatic resection to a mortality of less than 5 %
in large volume centers [35]. Patients undergoing resection will have
a 5 year survival of 10 to 70 % [1,30,32,35,36]. Multiple or large size
lesions are not contraindications to resection in and of themselves.
However, resection is contraindicated with tumor invasion of the main
portal trunk, common hepatic artery, or inferior vena cava. Traditional
chemotherapy alone induces minimal response and no survival
advantage, while modern targeted therapies have shown minimal
survival benefit [29]. Transarterial chemoembolizaiton (TACE),
radiation therapy, ablation, and radiospheres will be discussed in more
detail elsewhere in this issue.
Surgical management and indications are different for those with
normal liver parenchyma and for those with fibrosis or cirrhosis. Our
mandate at surgery is to leave enough functional liver to sustain life, but
this clearly depends on the health of the liver prior to surgery. Five to 40
% of HCCs are found in non-cirrhotics, depending on the population
studied [6,8]. For these patients, resection is the treatment of choice
regardless of lesion size or number so long as two adjacent segments
with blood inflow and outflow and intact biliary drainage remain after
surgery. In general, at least 20 % of pre-resection functional liver volume
is required to avoid post hepatectomy failure in those without fibrosis
or cirrhosis. The term "functional liver remnant" (FLR) is used to refer
to the segments of liver that will be left after a resection. A patient with
minimal liver injury (for example stage 2 fibrosis) can generally tolerate
an FLR of 40% [37]. The remaining HCC develop in cirrhotic livers. For
these cases surgical decision making is more nuanced. The expectation
of tumor progression should be weighed against the dangers of
ongoing liver failure in consideration of appropriate therapy. Portal
hypertension makes surgical and post surgical care challenging and low
liver function to liver volume ratio allows less aggressive resections due
to an increased incidence of postoperative hepatic failure. Guidelines
suggest resection in cirrhotics only for those with small lesions, normal
bilirubin and with no or minimal portal hypertension [9,32]. In our
experience, good outcomes can be expected in those with liver disease
when resection removes no more than 2 segments, bilirubin is less than
3 and there is neither portal hypertension nor ascites.
Even with appropriate resection and clear margins, because the
cirrhotic liver represents a 'field defect', there is high likelihood of new
or recurrent disease after resection of portion of the liver containing a known HCC [38,39]. In addition, the function of the remaining liver
is suspect in cirrhosis leading to greatly increased risk of liver failure
after resection. Both the 'field defect' and liver failure are treated with
orthotopic liver transplantation (OLT), which may be curative in
those with HCC and cirrhosis. As discussed below, when appropriate
and available, OLT is the preferred therapy for those with HCC and
cirrhosis.
Tumor recurrence is common in patients with resected HCC,
particularly when microvascular invasion or satellite nodules are
found on pathologic analysis of the surgical specimen [38,40,41].
Multimodality treatment including repeat resection may lead to
prolonged survival in patients with recurrent disease, but are not
generally curative.
While resection offers the best chance for cure for HCC in selected
patients, it comes with the highest risk and requires careful preoperative
assessment of both liver function and the patient's functional status. For
patients with resectable disease, normal or near normal liver function
and sufficient physiologic reserve, resection can be curative. We utilize
non-resective therapies to palliate or convert unresectable disease, or as
a bridge to OLT when appropriate.
Indications for orthotopic liver transplant (OLT) in HCC
In cirrhotic patients with HCC, recurrence is high due to a 'field
defect', and morbidity after resection is much higher in cirrrhotics than
in non cirrhotics. OLT treats two life threatening issues:
1) HCC recurrence within the liver
2) Underlying risk of death from chronic liver disease (for example
variceal bleeding, ascites, etc)
For these reasons, in selected patients with cirrhosis and HCC,
survival is better for those for whom orthotopic liver transplantation
is performed than for those treated with resection [42,43]. Generally
referred to as the Milan criteria, patients with cirrhosis and HCC may
be candidates for transplantation if they have a single lesion of less than
5 cm diameter or 2 or 3 lesions none greater than 3 cm in diameter and
with no gross vascular invasion [44]. (Table 1) A recent retrospective analysis of patients treated within these criteria found a 66 % 5 year
recurrence free survival in those who had OLT versus 26 % after
partial hepatectomy [45]. Interestingly, a recent report using criteria
which included larger lesions has shown similar survival [46]. In 2002,
to prioritize patients waiting for OLT, use of the model for end stage
liver disease (MELD) score (derived from measurement of INR, total
serum bilirubin and serum creatinine) was implemented to guide organ
allocation. Since then, because the MELD score does not consider
progression of malignant disease in those with adequate liver function,
changes were made in the selection process to add MELD points for a
diagnosis of HCC [47]. Though there have been a number of changes
in the system since 2002, currrently a diagnosis of HCC earns a score
of 22 points for those with stage II HCC. Acccording to current UNOS
guidelines, those with stage I, III and IV disease do not receive extra
MELD points for the diagnosis, though these exclusions are a matter of
significant debate [48,49].
Table 1 : Lowe, Jeyarajah
Thus, resection and OLT are the two potentially curative options
for patients with HCC, while other modalities are largely adjuvant or
palliative [29]. When the risk of death from progression of liver disease
is less than risk of undergoing surgery, hepatectomy is the treatment
of choice in those with HCC. However, in cases where ongoing liver
disease is a greater threat to life than that posed by surgery and where
resection increases the likelihood of liver failure, OLT should be used to
treat both the cancer and the liver disease.
Non-curative treatments of HCC
In patients with small tumors, radio frequency ablation (RFA) or
microwave ablation (MA) may allow long term survival. However,
local recurrence rates are high in those with tumors greater than 3 cm,
when the tumor is close to a major vessel, or when done laproscopically
or percutaneously, limiting the use of RFA or MA as a curative
therapy[50,51]. In patients whose liver disease is or will become life
threatening, TACE, RFA or MA may serve as a bridge to transplantation
[52-54]. RFA, MA or intra-arterial treatments may allow local control
in a palliative setting and in some patients may down stage disease
sufficiently to make unresectable disease resectable [55]. (Figure 2).
Figure 2: Reduction in size of a large hepatocellular carcinoma (HCC) before (A) and after (B) transarterial chemoembolization (TACE) in a 45 year old man who ultimately underwent right hepatectomy.
In summary, Western HCC develops most commonly in the
context of cirrhosis. Minimal resections can be performed in this
patient population, but careful thought should be given to OLT because
OLT will treat the underlying liver disease-related mortality and the
HCC-related mortality.
Colorectal liver metastases
Approximately 25% of patients diagnosed with colorectal
cancers will present with liver - only metastases at the time of initial
presentation and 50% of patients with colorectal cancer will develop
liver metastasis during the course of their disease. Of those diagnosed with liver metastasis at presentation 20% will be candidates for
surgery. Effective treatment of colorectal cancer with liver metastases
may require any or all of the following, neoadjuvant and/or adjuvant
systemic chemotherapy, transarterial chemo- embolization (TACE),
resection of the primary and/or liver metastasis, re-resection of liver
metastasis, portal vein embolization, surgical or percutaneous ablation,
or radioactive partical infusion (y90). As many of these options are not
mutually exclusive, we advocate a multidisciplinary approach to the
treatment of CRLM.
Rational for resection of colorectal liver metastasis
In contrast to other types of cancers in which metastatic disease is
not resected for cure, survival benefit and possible cure is achievable by
resection of colorectal disease which has liver only metastases [56,57].
In fact, patients without resection of CRLM have a mean survival of
5-13 months, while 5 year survival after resection is as high as 71 %
in those with single liver lesions [58], and 5 year survival is achievable
even in patients with 4 or more CRLMs [59]. These improvements
in overall survival are also made possible by decreasing mortality
associated with liver resection performed at high volume centers over
the last two decades. Chemotherapy has increased survival in patients
with metastatic colorectal cancer, but cure is not possible without
surgical resection. All patients with CRLM should be evaluated by an
experienced HPB surgeon to ensure that they are not, or can never be,
a surgical candidate. There are many adjuncts available to make even
initially unresectable lesions resectable, and therefore the decision to
not offer patients surgery should only be made by a surgeon that is
comfortable with major liver resections and who is familiar with other
modalities such as portal vein embolization (PVE)- see below.
Indications for resection of colorectal liver metastases
As is the case in planning resection for HCC, the number and size of
tumors do not play directly into the decision whether or not to perform
hepatactomy for CRLMs. Rather, potentially resectable CRLMs are
defined by the expectation of an R0 resection which will preserve two
contiguous liver segments with adequate inflow, outflow and biliary
drainage with an FLR of greater than 20% - 30% of preoperative
volume. In 2004 the EORTC 40983 trial included for resection those
patients with 4 or fewer CRLMs [60]. Most liver surgeons have not
followed these criteria in practice however, preferring to focus on
disease clearance and adequate remnant liver volume irrespective of the
number of metastasis [61]. Traditionally a margin of 1 cm has been the
standard for optimum clearance of tumor. However, similar outcomes
were seen in patients with microscopically negative margins less than
1 cm versus those with greater than 1 cm margins [62]. In addition to
anatomical evaluation for resection, tumor biology should be assessed
because the risks of resection may not be justified for a patient with a
tumor which is very likely to progress. Primary disease stage, rate of
rise of carcinoembyonic antigen (CEA), number and distribution of
CRLM, differentiation of the tumor and response to chemotherapy
may provide clues as to the likelihood of progression [63]. Fong et
al. developed a clinical risk score in which a node-positive primary,
less than 12 month diseases free interval, 2 or more metastases, CEA
greater than 200, and primary tumor larger than 5 cm, are associated
with decreased survival [64]. This and other scoring systems have been
shown to accurately predict survival in patients with CRLMs [65,66].
The surgical management of CRLMs differs from that of primary liver
tumors because the handling of the metastasis must be considered in
the context of treatment of the primary tumor. Our practice is to obtain
a CT of the chest abdomen and pelvis with IV contrast preoperatively to determine disease stage. Preoperative percutaneous biopsy is generally
not warranted in the context of known colorectal cancer and a typical
appearance on imaging, and has been associated with decreased survival
due to tumor dissemination [67]. We have found that for questionable
cases, MRI using the hepatocyte labeling contrast gadoxetate disodium
(EOVIST, Bayer HealthCare Pharmaceuticals Inc., Wayne, NJ) can be
very helpful in delineating number and distribution of metastasis and
in confirming the presence of non - hepatocyte containing solid tissue
masses (Figure 3).
Figure 3: A small colorectal lever metastasis is not apparent on CT (A), but is apparent on Eovist MRI.
Currently, patients with an expected FLR of greater than 20% and
who have favorable tumor biology should be considered for surgical
resection of CRLM. This decision should be made in the context
of a multidisciplinary conversation that includes the oncologist,
interventional radiologist and the HPB surgeon.
Evidence regarding chemotherapy prior to hepatectomy
Chemotherapy prior to liver resection can be given in the setting
of synchronously presenting primary and liver metastases, or after
a disease free interval following resection of the primary lesion. In
synchronous disease, preoperative chemotherapy may;
1) lead to smaller resections,
2) convert a non- resectable patient to resectable,
3) or identify patients with disease which will not respond to
chemotherapy, who will be poor candidates for aggressive surgical
therapy.
The reasons not to use chemotherapy preoperatively, but rather use
it only post - operatively, are:
1) lack of interruption of chemotherapy by surgery and possible surgical
complications,
2) hepatotoxicity of chemotherapeutic agents, and
3) the attendant increased risk of surgical complications after exposure
to chemotherapy
Data concerning outcomes relative to use of preoperative
chemotherapy have been contradictory. In the most severe cases
of oxaliplatin induced vascular lesions, operative bleeding and
transfusions were greater [68,69]. Oxaliplantin also induces steatosis
which has been linked to increased morbidity and infectious
complications [70,71] Steatohepatis related to iranotecan treatment was
linked to increased mortality due to liver failure, though these findings
have not been replicated [69]. Based on the findings of Karoui et al. in
which morbidity was increased in patients who received more than 6
cycles of chemotherapy preoperatively, it is our practice to operate after
3-6 cycles of systemic chemotherapy [72]. The value of this approach
has been recently confirmed by the EORTC intergroup RCT, in which
six cycles of FOLFOX plus resection improved survival versus surgery
alone [60]. Concerns that the VEGF receptor blocker bevicizumab may
have an additive effect on liver damage have not borne out [73,74].
Management of synchronous CRLMs
Management of synchronously presenting primary colorectal
mass and liver metastasis presents the unique problem of multiple
options for the chronologic staging of systemic chemotherapy, local
radiologic techniques and liver and colon resections. In the presence of
an obstructing or bleeding colon lesion, decision making is simplified
by the urgent presentation. In cases that do not present with emergent
complications, some authors suggest immediate liver resection to avoid
the surgical morbidity associated with preoperative chemotherapy.
Evidence and personal experience suggest that these morbidities can
be avoided by performing resection after no more than 6 cycles with
oxaliplatin based therapy [72]. The advantages of giving neoadjuvant
chemotherapy were discussed above, but include potential shrinkage of
tumor and avoidance of unnecessary resection in those with aggressive
disease. Consensus is lacking regarding the timing of surgery to remove
the primary tumor and the metastases. Currently, our preference is to
perform 3-6 cycles of oxaliplatin based chemotherapy prior to liver
resection. The liver is then considered the first order of concern and we
resect the liver metastases first if possible. The role of combined colon
and liver resections are a topic of debate [75,76]. It is our preference
to perform synchronous colon and liver resections if the patient is fit
and the liver resection has gone well with minimal blood loss. A staged
approach allows frequent re-evaluation of disease biology and patients
specific intervention with regard to timing and dose of chemotherapy.
When the primary tumor is in the rectum, we advocate sequencing
in radiation therapy after liver resection and completion of FOLFOX
based chemotherapy. PVE may become important to maximize FLR
when the liver is exposed to extensive chemotherapy prior to resection see
below.
Portal Vein Embolization
As discussed above, resection may not be an option for patients
with large or multiple lesions due to inadequate FLR. In an attempt
to increase the number of patients who can benefit from resection,
portal vein embolization has been used in some patients with predicted
borderline FLR [77]. Occluding portal vein flow to the diseased hemiliver
causes atrophy of the embolized segments and hypertrophy of
the contralateral liver [78] (Figure 4). This occurs quickly. Within
three weeks of PVE there will be demonstrable growth in the FLR.
(Figure 5) Despite the fact that fibrotic and cirrhotic livers have
impaired regeneration capacity, increase in functional liver remnant
does occur in diseased livers after PVE. In fact, PVE may be more
useful prior to resection of diseased livers than in those with normal
liver parynchyma. Failure of the contralateral liver to hypertrophy is a negative predictive factor for liver failure after resection [79]. (Figure 6)
Current practice suggests PVE in cirrhotic livers where the FLR will be
less than 40 % and PVE for an estimated FLR of less than 20-30 % in
those without parenchyma liver disease [77,80]. Due to chemotherapy
related liver injury, PVE is suggested for those who have been treated
with chemotherapy and have a predicted FLR less than 40 % [77]. For
CRLMs or neuroendocrine tumors, planned PVE with repeat resection
or ablation may allow a disease free liver remnant in patients who
would otherwise be unresectable (Figure 7).
Figure 4: Venogram before (A) and after (B) portal vein embolization (PVE) of right side portal branch.
Figure 5: Increase in size of left hemi liver after right side portal vein embolization (PVE). The area of the left hemi liver at the level of the portal vein confluence increased from 9 cm x 9.6 cm (A) to 10.3 cm x 11.5 cm (B)
Figure 6: Decision tree for operation after portal vein embolization(PVE). Hypertrophy after PVE may allow surgery. No hypertrophy portends poor outcome.
Figure 7: Staged resection of multiple metastases. This liver contains three large right side and 2 small left side lesions (A). In one possible scenario, the right portal vein is embolized and the small left sided leasions are treated with radiofrequency ablation (B), allowing staged resection of the right hemi-liver and resulting disease free, adequate sized functional liver remnant (FLR) (C).
In summary, resection is the only modality that can provide a cure
for patients with CRLM. Chemotherapy can prolong life but cannot
cure patients with CRLMs. Bilobar and extensive disease are not a
contraindication for resection in patients who have favorable tumor
biology otherwise. PVE and other adjuncts can result in allowing
resection of marginally resectable lesions.
Neuroendocrine liver metastasis
Neuroendocrine liver metastases (NLM) develop in 46 % to 93
% of patients with neuroendocrine malignancy, and the diagnosis of
neuroendocrine disease is often made when hormone production by intrahepatic metastases overwhelms the metabolic clearance of hormone
by the liver itself. Metastatic disease is often multifocal, but morbidity
and mortality more often results from excessive hormone production
than by tumor invasion of normal tissues.
Rational for resection of neuroendocrine liver metastasis
NLM have a limited response to systemic chemotherapy
with the presence of liver metastasis being the most significant
predictor of outcome [81]. Other non - surgical approaches such as
131I-metaiobenzylguanidine (MIBG) therapy and and 111 In-octreotide
therapy have a limited duration of response. Resection represents the
only hope for long term survival benefit and prolonged improvement
in symptoms.
Indications for resection of neuroendocrine liver metastases
Because NLM are often multifocal, only 10 %-20 % of patients with
NLM are candidates for surgical removal of all metastases, however,
prolonged symptom free survival can be expected if at least 90% of
metastasis are resected or ablated [82,83]. Though metastatic recurrence
occurs in up to 80%, the overall indolent nature of the disease allows
for long symptom free intervals and prolonged survival after surgical
treatment. However, non-functional NETs are more often associated
with high grade malignancy and worse survival when compared with
functional NETs [84]. Large and small cell tumors also have particularly
aggressive biology [85]. For all tumor types, current recommendations
are for complete resection of disease provided an adequate FLR remains,
and surgical de-bulking if at least 80-90 % of tumor mass can be
removed and symptoms are severe in spite of non-operative treatment,
or if mass effect threatens survival [30,82,83,86]. Surgical debulking can
be used in conjunction with RFA or MA to provide symptomatic relief
when resection alone cannot remove sufficient tumor [87,88].
Surgical therapy for neuroendocrine liver metastases
Similar to operation for CRLM, resection is warranted when
disease can be removed leaving a tumor free FLR of at least 20 %
and with adequate blood inflow and outflow. Surgical debulking with
or without ablation can effectively relieve symptoms and prolong
survival when complete removal of all diseased liver is not possible, or
when extra - hepatic metastases exist. However, experience suggests
high recurrence when NLM larger than 3 cm are treated with RFA
[89,90]. Adjuvant treatment with octreotide or interferon a decreases
symptoms after resection or ablation [91]. NLM derive their blood
supply almost exclusively from the arterial system allowing directed
treatments via cannulation of the hepatic artery and its branches
[92]. For non-resectable disease, hepatic arterial therapy may provide
symptomatic relief and increase survival [92-95]. Experience with OLT
for neuroendocrine liver metastases has been limited, but suggests
worse outcomes than those for other indications [96].
In summary, NLMs occur in a majority of patients with
neroendocrine tumors, but a small proportion of patients are suitable
for liver resection. However, when possible, liver resection for NLMs
can allow prolonged symptom free survival. Medical therapies provide
only limited symptom free intervals and are not curative in intent. OLT
does not likely improve outcomes for NLMs.
Conclusion
Treatment of primary and metastatic liver tumors requires
navigation of complex decision trees which rely on multimodality
treatment options. For HCC, the only potentially curative treatment options are resection and OLT. For single HCC tumors in patients with
normal liver function, resection provides equivalent of better long term
survival to OLT. However, when liver disease threatens survival, OLT
is the treatment of choice. Current selection criteria weigh heavily in
favor of those with stage 2 HCC, leaving many patients unlikely to
undergo OLT.
Resection of CRLMs can also lead to long term survival. Even
in those who do not achieve cure, our increasing competence with
multimodality treatment of CRLMs has led to a paradigm shift such
that CRLMs are increasingly a disease patients live with, rather than die
from. Though many NLMs will recur, long term survival is the norm
after resection because of a general indolent biology. OLT does not
improve survival in metastatic disease.
OLT is the best option for HCC when criteria are met. However,
when OLT is not an option, and complete removal of all known disease
is possible via a liver resection which leaves adequate liver volume to
support life, resection is the gold standard. Mutlimodality treatment via
TACE, ablation, PVE, radioembolization and other local therapies can
act as a bridge to transplantation in HCC and can sometimes convert non
resectable patients with HCC or metastatic disease. We regard ongoing
multimodality assessment, and early involvement of an experienced
surgeon as standard of care for those with primary or metastatic liver
tumors. Thus, resection and OLT are the two potentially curative options
for patients with HCC, while other modalities are largely adjuvant or
palliative [29]. When the risk of death from progression of liver disease
is less than risk of undergoing surgery, hepatectomy is the treatment
of choice in those with HCC. However, in cases where ongoing liver
disease is a greater threat to life than that posed by surgery and where
resection increases the likelihood of liver failure, OLT should be used to
treat both the cancer and the liver disease.
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