Surgical Management

11/29/21, 11:00 PM Surgical management of potentially resectable hepatocellular carcinoma - UpToDate
Authors: Steven A Curley, MD, FACS, Carlton C Barnett, Jr, MD, Eddie K Abdalla, MD, FACS
Section Editors: Stanley W Ashley, MD, Kenneth K Tanabe, MD
Deputy Editor: Wenliang Chen, MD, PhD
Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Oct 2021. | This topic last updated: Oct 26, 2021.
INTRODUCTION
Hepatocellular carcinoma (HCC) is a tumor with highly variable biology that often occurs in the
setting of chronic liver disease and cirrhosis. It is typically diagnosed late in its course, and the
median survival following diagnosis is approximately 6 to 20 months [1]. The mainstay of
potentially curative treatment for hepatocellular carcinoma is surgical resection, but several
other treatment modalities may also have a role. In properly selected and prepared patients,
hepatectomy for hepatocellular carcinoma may be an option, even in patients with underlying
cirrhosis. Patients with more advanced disease who undergo major hepatic resection have
improved outcomes compared with those who are not candidates for other treatments
because of disease extent, including transplantation. Resectable patients with early HCC and
underlying liver disease are increasingly being considered for transplantation because of
potential for better disease-free survival and resolution of underlying liver disease, though
this approach is limited by organ availability, especially in resectable patients.
Options for surgical resection are in part determined by the severity of underlying liver
disease, which is reflected by the Child-Pugh classification ( table 1) or the Model for End-
stage Liver Disease (MELD) score, which is a prospectively developed and validated chronic
liver disease severity scoring system to predict survival (calculator 1). (See "Assessing surgical
risk in patients with liver disease", section on 'MELD score and Mayo risk score' and "Model for
End-stage Liver Disease (MELD)".)
Surgical resection of HCC will be reviewed here. The clinical manifestations and diagnosis of
HCC, an overview of the treatment approach to HCC, nonsurgical local ablative options, liver
transplantation, and adjuvant and neoadjuvant therapy are reviewed elsewhere.
● (See "Epidemiology and risk factors for hepatocellular carcinoma".)

● (See "Overview of treatment approaches for hepatocellular carcinoma".)
https://www.uptodate.com.asmphlibrary.remotexs.co/contents/surgical-management-of-potentially-resectable-hepatocellular-carcinoma?search=extended hepatecto… 1/28

● (See "Nonsurgical therapies for localized hepatocellular carcinoma: Radiofrequency

ablation, laser and microwave thermal ablation, percutaneous injection therapies,
cryoablation, high-intensity focused ultrasound, and irreversible electroporation".)
● (See "Liver transplantation for hepatocellular carcinoma".)
● (See "Management of potentially resectable hepatocellular carcinoma: Prognosis, role of
neoadjuvant and adjuvant therapy, and posttreatment surveillance".)
TREATMENT ALGORITHMS FOR HCC
A general approach to treatment to hepatocellular carcinoma (HCC) is shown in the figure (

algorithm 1). The suggested approach is useful for conceptualizing the various treatment
options that are available for individual patients but may not be applicable in all settings. A
discussion of these issues and an overview of available therapies for HCC are summarized
elsewhere. (See "Overview of treatment approaches for hepatocellular carcinoma".)
IMPORTANCE OF COMPREHENSIVE MULTIDISCIPLINARY CARE
A majority of patients with hepatocellular carcinoma (HCC) have an underlying liver disease,
such as hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection (more common in the
United States), or nonalcoholic fatty liver diseases (NAFLD). Management of NAFLD is
particularly challenging because many patients have concomitant viral hepatitis in addition to
obesity [2-5].
Furthermore, patients with chronic liver disease who undergo any form of therapy for HCC are
at high risk for recurrent disease and progression to liver failure. It is important that patients
with more advanced liver disease have proper monitoring and assessment of their underlying
liver disease, which may have a major impact on longer-term survival. Prognostic scoring
systems to assess the severity of underlying liver disease in patients undergoing treatment for
HCC are discussed in detail elsewhere. (See "Staging and prognostic factors in hepatocellular
carcinoma", section on 'Staging and prognostic scoring systems'.)
Establishment of a multidisciplinary HCC clinic has been associated with improved clinical
outcomes [6]. Comprehensive care of patients with cirrhosis includes antiviral therapy for HBV
and HCV, immunization against hepatitis A and HBV (if indicated), and endoscopic screening
and surveillance for varices. (See "Epidemiology and risk factors for hepatocellular carcinoma"
and "Cirrhosis in adults: Overview of complications, general management, and prognosis".)

PREOPERATIVE ASSESSMENT
Curative partial hepatectomy is an optimal treatment for hepatocellular carcinoma (HCC). The
assessment of potential resectability of HCC focuses on two main issues:
● The likelihood of the disease being confined to the liver (except fibrolamellar subtype of
HCC). (See "Epidemiology, clinical manifestations, diagnosis, and treatment of
fibrolamellar carcinoma".)
● Whether the size and location of the tumor relative to the patient's underlying liver
function will permit resection without excess morbidity and mortality.
Patients ideally suited for resection have localized HCC confined to the liver without
radiographic evidence of invasion of the vasculature of the liver ( image 1), preserved
hepatic function, and no evidence of portal hypertension (although a minor resection could be
considered in some patients with portal hypertension) [7-9]. Resection can provide benefits for
some patients with multifocal disease or those with major vascular invasion, although
outcomes are less favorable [10,11]. (See "Staging and prognostic factors in hepatocellular
carcinoma", section on 'Clinical implications'.)
Only one-half of patients initially thought to be resectable and referred for surgery actually
have resectable tumors. Among the reasons for unresectability are the extent of intrahepatic
disease, extrahepatic extension, inadequate functional hepatic reserve, and involvement of
the confluence of the portal or hepatic veins [12,13].
Despite even aggressive surgical approaches, most patients have disease (either HCC or
underlying chronic liver disease) that is too extensive to permit treatment with "curative"
intent. In high-incidence regions of the world, only 10 to 15 percent of newly diagnosed
patients are candidates for standard resection, whereas in low-incidence areas, between 15
and 30 percent of patients have potentially resectable disease [13-15]. (See "Epidemiology and
risk factors for hepatocellular carcinoma".)
Determining the extent of tumor involvement — Anatomic delineation of tumor extent is

best achieved with dynamic multiphase computed tomography (CT), for which the
nonenhanced, hepatic arterial phase is assessed separately from the portal venous phase and
a late "wash-out" phase. Small HCCs are often isodense to the liver in the portal venous phase
and may be missed on a conventional "screening" CT [16]. In contrast, arterial phase imaging
detects 30 to 40 percent more tumor nodules than conventional CT and may be the only phase
needed to demonstrate the tumor in 7 to 10 percent of cases [17,18].

MRI appears to be as accurate, or more accurate, than CT in liver staging for HCC using both
multiphasic and multiparametric imaging (combining T1, T2, and diffusion-weighted imaging
with dynamic multiphasic imaging). Several studies have shown MRI to be superior to CT for
detection of HCC, particularly in cirrhotic livers and particularly for correct diagnosis of smaller
nodules [19-21]. MRI with hepatocyte-specific contrast agents (eg, gadolinium-based agents
such as Gd-BOPTA and Gd-EOB-DTPA) may increase lesion detection, improve lesion
characterization, and may be useful in the detection of recurrence as well [22-24].
The role of other imaging studies in the evaluation of primary HCC, including positron
emission tomography (PET) with conventional and novel agents and CT arteriography, is
discussed in detail elsewhere. In general, these studies add little to thin-slice, multiphasic
imaging except in highly selected cases. (See "Clinical features and diagnosis of hepatocellular
carcinoma", section on 'Evaluation after HCC Diagnosis'.)
Although characterized in few reports, the recognized sites of metastatic spread of HCC are
lung, bone, peritoneum, and adrenals. Although these sites of disease may be demonstrated
by standard imaging techniques, peritoneal disease is frequently missed. The rate of
extrahepatic disease spread at diagnosis is overall low, and staging chest CT and bone scans
do not provide additional information on metastases in patients who have localized HCC. The
utility of 18-fluorodeoxyglucose positive emission tomography (FDG-PET) scanning for
detection of otherwise occult distant metastatic disease is uncertain and not recommended in
guidelines from the National Comprehensive Cancer Network (NCCN) [25]. (See "Clinical
features and diagnosis of hepatocellular carcinoma", section on 'Evaluation after HCC
Diagnosis'.)
However, the risk of extrahepatic metastatic disease is higher in patients with a tumor that is
large (>5 cm), is located at a subdiaphragmatic location, or demonstrates vascular invasion.
Patients who have such tumors warrant additional imaging studies or diagnostic laparoscopy
prior to resection, particularly if they have worrisome symptoms such as bone pain.
There is no general rule regarding tumor location, size, or number in selecting patients with
HCC for resection; however, most consider stage IIIB, IVA, and IVB disease to be incurable by
resection ( table 2). These stages are defined by invasion of a major portal or hepatic vein,
direct invasion of organs other than the gallbladder, perforation of the visceral peritoneum,
and nodal or distant metastases. However, hepatic resection for stage IIIB and IVA disease
may be considered in a center of excellence because clinical benefits and long-term survival
can be achieved in a properly selected, though admittedly small, minority of patients.

Advances in the surgical management of HCC have expanded the indications for curative
hepatectomy, including more extensive liver resections [26].
The impact of size, multifocality, regional nodal involvement, and tumor rupture on
resectability is debated:
● Patients with small tumors are less likely to harbor occult vascular invasion and have a
better outcome after surgery. Patients with a solitary HCC without vascular invasion have
a similar survival regardless of tumor size ( figure 1) [8,10,27-36].
● Although some surgeons restrict eligibility for resection to patients with tumors that are
≤5 cm in diameter, most centers do not use size alone to select patients for resection
[10,37,38].
• Outcomes for patients with large tumors were studied in a multi-institutional series of
300 patients undergoing resection for HCC ≥10 cm [10]. The five-year overall survival
rate was 27 percent for all patients combined. In multivariate analysis, four clinical
factors (serum alfa-fetoprotein [AFP] ≥1000 ng/mL, multiple tumor nodules, presence
of major vascular invasion, and presence of severe fibrosis) were independent
predictors of poor outcome. Five-year survival rates were significantly worse for
patients with one or two, or three to four, risk factors compared with those with none
(19, 14, and 49 percent, respectively). However, these clinical factors were not reliable
predictors of outcome. Fifty-six percent of patients with one or two risk factors and 20
percent of those with three or four risk factors had T1 or T2 disease on pathologic
evaluation.
• In another multicenter retrospective review of 1115 patients with HCC, major

hepatectomy was performed in 539 patients, for which the mean tumor size was 10
cm (range 1 to 27 cm) [26]. The tumor, node, metastasis (TNM) stage distribution was
29 percent stage I, 31 percent stage II, 38 percent stage III, and 2 percent stage IV.
Five-year survival rates improved for each successive cohort at 30 percent for 1981 to
1989, 40 percent for 1990 to 1999, and 51 percent for 2000 to 2008. Perioperative
mortality also improved. In multivariate analysis, factors significantly associated with
worse outcomes included earlier time period, AFP level >1000 ng/mL, tumor size >5
cm, presence of major vascular invasion, presence of extrahepatic metastases, and
positive surgical margins.
• In a prospective study of over 11,000 patients undergoing hepatectomy for HCC from
2002 to 2010 in Taiwan, patients with small (<3 cm), medium (3 to 4.9 cm), large (5 to
10 cm), and huge (>10 cm) tumors had five-year overall survival rates of 72, 62, 51,
and 35 percent, and 10 year overall survival rates of 53, 42, 36, and <20 percent,
respectively [39]. Known factors that are predictive of poor outcomes, such as
inadequate margins of resection, poor differentiation, multiple tumors, vascular
invasion, and cirrhosis, also applied to patients with huge HCC.
• Although the presence and degree of vascular invasion portends increased risk for
recurrence and is a powerful predictor of survival post-resection, microvascular
invasion in small tumors has a lesser impact on outcome and may be predicted from
preoperative parameters [40]. In the latest iteration of the American Joint Committee
on Cancer (AJCC) staging system, T1 classification includes not only solitary tumors of
any size without vascular invasion but also tumors ≤2 cm with or without
microvascular invasion ( table 2) [41].
● Multifocality increases the T classification ( table 3) and is associated with lower

survival but does not exclude a good outcome in selected patients. In several studies,
resection of multifocal HCC was associated with five-year survival rates of approximately
24 percent [28,42,43]. Patients with multinodular HCC who appeared to benefit from
resection were those with sufficient liver reserve to tolerate resection, without
extrahepatic disease, and without major vascular invasion. Size alone is not a
contraindication for resection of multinodular HCC. Unfortunately, many patients have
multifocal disease that is underestimated even by high-quality CT and magnetic
resonance imaging (MRI).
● Lymph node metastases are uncommon overall (between 1 and 8 percent), but their
presence portends a worse outcome [44,45]. Preoperative detection of nodal metastases
is limited by the frequent presence of benign nodal enlargement, most often involving
the porta hepatis and portacaval space, in patients with cirrhosis [46]. Highly suspicious
nodes based on enhancement similar to the intrahepatic HCC lesions indicate the need
for biopsy in a patient being considered for resection. Outcomes are worse in patients
who have regional nodal involvement. Although practice is variable [47-50], we consider
that documented regional (portal) nodal involvement precludes potentially curative
resection for hepatocellular carcinoma. However, lymph node involvement is not a
contraindication to resection for patients with fibrolamellar HCC; these patients undergo
a formal lymph node dissection. Prior to planned hepatic resection, exploratory
laparoscopy and intraoperative ultrasound may help identify extrahepatic metastatic
disease that precludes hepatic resection. (See 'Intraoperative staging' below and "Open
hepatic resection techniques", section on 'Staging laparoscopy and use of ultrasound'

and "Epidemiology, clinical manifestations, diagnosis, and treatment of fibrolamellar

carcinoma", section on 'Potentially resectable disease'.)
● Approximately 10 percent of HCCs spontaneously rupture. The clinical picture is that of

acute abdominal pain and distension, hypotension, and a drop in the hematocrit.
Initially, these patients should be stabilized hemodynamically, followed by transarterial
embolization for control of bleeding. If unsuccessful, emergency surgery may be
required [51]. (See "Clinical features and diagnosis of hepatocellular carcinoma", section
on 'Clinical features'.)
Although the presence of a tumor rupture suggests a high likelihood of peritoneal

seeding and usually a poor outcome from resection, this is not inevitable [52,53]. If
bleeding can be controlled with embolization, a formal staging evaluation should be
undertaken, followed by laparoscopic exploration and a subsequent attempt at resection,
if feasible [54]. Several retrospective series suggest a low but defined long-term survival
rate following resection in such situations [54-60]. In a large case series, the 30 day
mortality rate in 154 of 1716 patients who were newly diagnosed with HCC after
presenting with spontaneous rupture was 38 percent [55]. After initial stabilization and
clinical evaluation, 33 underwent hepatic resection. Although the median survival after
hepatectomy was worse in ruptured compared with nonruptured cases (26 versus 49
months) and the rate of extrahepatic recurrence was higher (46 versus 26 percent), eight
patients (24 percent) remained alive without recurrent disease after a median 45 month
follow-up.
For patients with liver-confined HCC who are not candidates for standard resection, alternative
treatment modalities include interstitial therapies; transarterial chemoembolization (TACE);
transarterial radioembolization (TARE, embolization with particles emitting radiation); localized
ablative techniques involving either freezing or cryoablation; chemical desiccation (eg, ethanol
or acetic acid ablation); or heating with laser, microwave, or radiofrequency ablation (RFA).
These nonsurgical local ablative treatments are discussed elsewhere. A general treatment
algorithm for HCC is presented in the figure ( algorithm 1). In addition, various
combinations of embolic therapy, ablative therapy, and surgery are being considered. (See
"Nonsurgical therapies for localized hepatocellular carcinoma: Radiofrequency ablation, laser
and microwave thermal ablation, percutaneous injection therapies, cryoablation, high-
intensity focused ultrasound, and irreversible electroporation".)
Assessment of hepatic reserve — Operative mortality for HCC is related to the severity of the
underlying liver disease, being twice as high in cirrhotic as in noncirrhotic patients (10 versus 5
percent, respectively) [61]. With proper patient selection, operative mortality, even in cirrhotic
patients, should be low [62]. However, only approximately 5 to 15 percent of patients

presenting with HCC will have adequate hepatic reserve to undergo resection [63]. As a
general rule, patients who have complications of cirrhosis, such as bleeding, ascites, or
marked portal hypertension, have insufficient hepatic reserve to withstand a partial
hepatectomy, although there are exceptions [64].
In patients with cirrhosis, surgical resection is most safely performed in those with Child-Pugh
class A disease ( table 1) who have a normal bilirubin level and well-preserved liver function.
However, even Child-Pugh class A patients may develop rapid hepatic decompensation
following surgery due to limited functional hepatic reserve. In one study of 29 such patients
with HCC who underwent resection, 11 (38 percent) developed liver failure that was
unresolved three months postoperatively [9]. Although helpful, the Child-Pugh classification
and other tools for assessing underlying liver disease, such as the Model for End-stage Liver
Disease (MELD) score (calculator 1), are not adequate for predicting patients with sufficient
hepatic reserve for major resection. (See "Assessing surgical risk in patients with liver disease",
section on 'MELD score and Mayo risk score'.)
The volume and function of residual liver remnant can be determined using hepatic
volumetry, which can be performed prior to and following portal vein embolization, which can
be used in selected patients to increase the volume of the liver remnant prior to major hepatic
resection [65,66]. Portal vein embolization is discussed in detail below. (See 'Portal vein
embolization' below.)
Increasingly, functional analyses in conjunction with CT volumetry are gaining acceptance

when major resection is considered. As examples, combined volumetric-functional assessment
using technetium hepatobiliary scintigraphy may be more accurate than volumetry alone in
assessing risk for liver insufficiency/failure and mortality after major liver resection [67,68].
Alternatively, many groups (especially in Asia) use clearance of indocyanine green (ICG-15) at
15 minutes as a defining criterion for selection of resection type [69]. Absence of portal
hypertension as measured by the wedged hepatic venous pressure gradient may also be
helpful [9]. However, these techniques have been widely adopted and are not yet considered
the current standard of care in North America.
Portal vein embolization — Preoperative portal vein embolization (PVE) is a valuable adjunct

to major liver resection, particularly for right-sided tumors [65,70-73]. PVE can initiate
hypertrophy of the anticipated future liver remnant and allow a more extensive resection. (See
"Overview of hepatic resection", section on 'Preoperative PVE and other alternatives' and
"Preoperative portal vein embolization", section on 'Introduction'.)

The benefits of PVE in patients with HCC were assessed in a meta-analysis of data from 37
published series of PVE prior to liver resection totaling 1088 patients (265 with HCC, the
remainder with cholangiocarcinoma or liver metastases) [71]. Four weeks after PVE, there was
an overall 10 to 12 percent increase in liver volume that was independent of technique, and 85
percent of patients underwent planned laparotomy for attempted major hepatectomy.
Reasons for not proceeding to surgery included inadequate hypertrophy of the remnant liver
in 18, severe progression of liver metastases (n = 43), extrahepatic spread (n = 35), or other
(refusal of surgery, poor medical condition, altered treatment approach for a variety of
reasons, etc; n = 35). Of the patients who underwent laparotomy, resection was not possible in
27, because of advanced, unresectable disease. Following resection, 23 patients had transient
liver failure (2.5 percent) with 7 patients dying of acute liver failure (0.8 percent).
The benefit of PVE was further shown in a retrospective series that compared outcomes
among patients who underwent major hepatic resection for HCC at a single institution with (n
= 21) or without (n = 33) PVE [74]. In the PVE group, the median standardized future liver
remnant volume pre- and post-PVE was 23 and 34 percent, respectively. Patients who
underwent PVE had fewer major complications (10 versus 36 percent) and no 90 day mortality
(compared with 18 percent for major resection without PVE). Overall survival at three years
with and without PVE was not significantly different at 82 and 63 percent, respectively.
Transarterial chemoembolization (TACE) has been proposed as a complementary procedure

prior to PVE in patients with HCC [74-83]. TACE eliminates the arterial blood supply to the
tumor and also embolizes potential arterioportal shunts that attenuate the effects of PVE in
cirrhotic livers [75,84]. Complementary improvements in safety and disease-free and overall
survival using combined TACE/PVE prior to resection have sparked further interest in this
therapeutic sequence prior to right hepatectomy for HCC in cirrhosis [74,75,84].
INTRAOPERATIVE STAGING
Laparoscopy and intraoperative ultrasound (IOUS) may improve the selection of patients for
potentially curative resection [12,85]. IOUS can accurately determine the size of the primary
tumor and detect lymph node or portal or hepatic vein involvement, which precludes curative
resection. In one series that included 91 patients with hepatocellular carcinoma (HCC) who
underwent laparoscopic IOUS prior to resection, a planned laparotomy was aborted in 16
percent because of unresectable disease [12]. Another benefit of IOUS is the identification of
major intrahepatic vascular structures, which can be used to guide segmental or nonanatomic
resections [86,87]. (See "Diagnostic staging laparoscopy: General principles for staging
primary digestive malignancies".)
HEPATIC RESECTION
The type of hepatic resection depends upon the location of the lesion(s) and presence and
severity of cirrhosis.
Anatomic versus nonanatomic resection — Anatomic resection of the liver is performed by

following the planes of the liver segments as delineated by Couinaud ( figure 2). Some
studies suggest that anatomic resections, when feasible, provide longer overall and disease-
free survival [88,89]. Anatomic hepatic resection is accomplished by selective ligation of the
inflow portal triad and ligation of dominant outflow hepatic veins to the segment(s) that will
be resected [90]. If subsegmental resection is planned, intraoperative ultrasonography
facilitates localization of the intrahepatic vessels [91-93].
Nonanatomic resection may be necessary to minimize the loss of functioning parenchyma in

patients with cirrhosis [94] (see "Open hepatic resection techniques", section on 'Specific
resections'). Although in the noncirrhotic liver up to two-thirds of functional parenchyma can
be removed safely depending upon the age of the patient, for cirrhotic patients, the resection
needs to remove the least amount of nonmalignant parenchyma possible to preserve
postoperative liver function ( picture 1). Because the capacity for liver regeneration is
impaired in cirrhotics, resection is generally limited to <25 percent of the functional
parenchyma. However, some patients maintain adequate functional hepatic reserve even after
a hemihepatectomy, particularly if preoperative portal vein embolization (PVE) is used to
induce compensatory hypertrophy in the future liver remnant (the region of liver that will
remain after resection). (See 'Portal vein embolization' above.)
One retrospective study compared anatomic versus nonanatomic resection for 658 patients
with hepatocellular carcinoma (HCC) without evidence of macroscopic vascular invasion who
underwent primary resection with curative intent. The surgical procedure was selected by the
surgeon based upon patient characteristics. There was no significant difference between the
two groups in recurrence-free survival, overall survival, or early recurrence rate within two
years after resection [95]. However, the incidence of microvascular invasion was higher in the
matched anatomical resection group. Future randomized trials are needed to directly compare
the two techniques. Until further data are available, most surgeons recommend anatomic
approaches when feasible and safe based on analysis of liver function.
No touch technique — Some surgeons have advocated an anterior or "no touch" technique

for the resection of HCC. This approach utilizes initial transection of the liver parenchyma to
the inferior vena cava (IVC) and ligation of the inflow and outflow vessels before mobilization

of the hemiliver. The advocates for this technique hypothesize that separation of the hemiliver
and tumor from the IVC before mobilization reduces the risk of vessel rupture and
theoretically minimizes the potential for tumor cell dissemination. A prospective trial of 120
patients (87 percent with underlying cirrhosis or hepatitis) directly compared this technique
with conventional resection [96]. Compared with the conventional technique, the anterior
approach was associated with less blood loss, lower transfusion requirements, significantly
longer median overall survival (>68 versus 23 months), and lower hospital mortality (1.7 versus
10 percent) [96]. However, recurrence and disease-free survival rates were similar between the
two groups. The results of this study have been questioned because the rates of massive
blood loss (28 percent) and perioperative mortality (10 percent) using the conventional
approach for HCC resection were higher than usually reported, which may reflect the larger
proportion of patients with cirrhosis or hepatitis in this series [97]. The liver can be lifted with a
tape, providing a tremendous technical advantage when addressing large tumors [98], and
many authors have found the technical advantage alone a reason to use the anterior
approach (with hanging maneuver). Though data are lacking to conclude that the anterior
approach is superior to conventional mobilization, the absence of a downside and significant
technical advantage provided by the anterior approach (particularly with the liver-hanging
maneuver) have led to widespread use of this technique in both open and minimally invasive
liver surgery.
Central hepatic resection — Surgical management of centrally located HCCs (ie, those in

segments IV, V, and VIII) is more problematic ( figure 2). Extended right or left
hemihepatectomy is the treatment of choice if potentially curative surgery can be undertaken
safely. However, these resections can be associated with high morbidity and mortality rates
due to insufficient residual functional liver parenchyma [99-101]. An alternative approach,
mesohepatectomy (also called central hepatectomy), is used in which the central liver
segments IV and/or V, and VIII (with or without segment I), are removed, leaving the lateral
sectors intact [102,103].
Although randomized trials have not been conducted, the available data suggest that
mesohepatectomy is a reasonable alternative to extended hepatic resection for centrally
located tumors, giving acceptable oncologic outcomes with less parenchymal loss [102,104-
107]. However, in some centers, mesohepatectomy is seldom used, partly because it is a
complex and technically demanding procedure that requires two hepatic resection planes and
bilateral biliary reconstruction [108]. This could result in a higher risk of bleeding and
postoperative bile leak as well as long-term biliary stricture and biliary dysfunction, although a
retrospective study using propensity score matching demonstrated comparable morbidity and
mortality rates after mesohepatectomy versus extended hepatic resection for malignant

tumors [109]. Data from other studies suggest that PVE followed by standard hepatectomy
might be a safer approach.
Minimally invasive hepatic resection — The success of minimally invasive resection of

benign hepatic tumors has led to interest in laparoscopic and robotic approaches to surgery
for HCC [110-119]. The available literature is steadily growing to fill the needed data gap
regarding long-term oncologic outcomes. The available data support the view that, in
experienced hands, laparoscopic or robotic resection is feasible and safe, but it is also highly
technically demanding and should be undertaken only in high-volume centers with a program
of graduated procedural complexity. One advantage of a minimally invasive approach may be
simplification of subsequent liver transplantation, if ultimately needed, due to fewer
abdominal adhesions after the initial resection of HCC [120]. A second advantage may be the
avoidance of division of abdominal wall collaterals associated with some abdominal incisions.
(See "Minimally invasive liver resection (MILR)".)
The following represents the range of findings in patients undergoing laparoscopic resection
for HCC:
● In a 2017 meta-analysis of 44 studies including over 5000 patients, laparoscopic liver

resection for HCC was associated with less blood loss and need for blood transfusion,
shorter hospital stay, higher R0 resection rate, wider resection margins, lower morbidity
rate, and lower 30 day mortality rates compared with open surgery. Operative time;
tumor recurrence rate; and one-, three-, and five- year overall and disease-free survival
rates were not different [121].
● In a 2018 systematic review of 17 studies published in the preceding 10 years, over 1500
patients underwent laparoscopic liver resection for HCC, most with good liver function
and a single HCC; 33 to 100 percent had cirrhosis as determined by pathology. Overall
perioperative mortality and morbidity ranged from 0 to 2.4 percent and 4.9 to 44
percent, respectively. The overall survival rates ranged from 73 to 100 percent at one
year, 61 to 94 percent at two years, and 38 to 90 percent at three years. Compared with
open surgery, laparoscopic resection was associated with shorter operative time, lower
complication rate, reduced blood loss and transfusion requirement, and a shorter
hospital stay [122].
POSTOPERATIVE MORBIDITY AND MORTALITY

Postoperative morbidity and mortality is related to the extent of operative resection [123-126].
The 30 day perioperative mortality rate in modern series of hepatocellular carcinoma (HCC)
resection ranges widely from 1 to 24 percent [26,27,29,127-131]. Consensus is growing that 30
day operative mortality is an inadequate indicator of risk, particularly of postoperative hepatic
insufficiency and failure. Using an approach similar to liver transplantation reporting, 90 day
mortality rates appear to be a more valuable indicator of outcome of liver resection, especially
in the cases of extended resection and resection in patients with diseased livers [132,133]. This
relates to the late development of slowly progressive jaundice, ascites, and eventual death,
which typically occurs outside the hospital and well after 30 postoperative days in patients
with marginal or inadequate liver remnants.
Most deaths are due to postoperative liver failure, and fewer than 10 percent are due to
complications from bleeding. The presence of cirrhosis is the most important predictor of
postresection liver failure and death. Major resection in cirrhotic patients without careful
selection and/or portal vein embolization (PVE) continues to be a major challenge. Series
assessing major resection in patients with cirrhosis without PVE continue to report mortality
rates up to 18 percent compared with <3 percent for those undergoing PVE [74]. Two
additional factors influence the development of postoperative liver failure in cirrhotic patients:
intraoperative blood loss of >1500 mL and postoperative infection of any type [131]. Mortality
can be reduced by appropriate selection of patients with the inclusion of preoperative
volumetry and portal vein embolization when appropriate, and meticulous surgical technique,
including techniques to minimize blood loss and the need for transfusion.
Major postoperative complications include bile leak and pleural effusion. As an example, in a
series of 416 patients who underwent liver resection, the most frequent complications were
bile leak (8 percent) and pleural effusion (7 percent). A postoperative intensive care unit stay
more than two days was required in 18 percent of patients, and the median hospital stay was
10 days [127]. (See "Overview of hepatic resection", section on 'Complications' and "Overview
of hepatic resection", section on 'Mortality'.)
POST-TREATMENT SURVEILLANCE AND LONG-TERM OUTCOMES
Models are being developed to predict the risk of recurrence after liver resection for
hepatocellular carcinoma (HCC) [134,135]. The long-term outcomes, benefit of adjuvant
therapy, and recommendations for post-treatment surveillance after potentially curative
resection are discussed in detail elsewhere. (See "Management of potentially resectable
hepatocellular carcinoma: Prognosis, role of neoadjuvant and adjuvant therapy, and

posttreatment surveillance" and "Staging and prognostic factors in hepatocellular

carcinoma".)
SPECIAL CONSIDERATIONS DURING THE COVID-19 PANDEMIC
The COVID-19 pandemic has increased the complexity of cancer care. Important issues in
areas where viral transmission rates are high include balancing the risk from delaying
diagnostic evaluation and cancer treatment versus harm from COVID-19, minimizing the
number of clinic and hospital visits to reduce exposure whenever possible, mitigating the
negative impacts of social distancing on delivery of care, and appropriately and fairly
allocating limited healthcare resources. Specific guidance for decision-making for treatment of
HCC during the COVID-19 pandemic is available from the International Liver Cancer
Association (ILCA). General recommendations for cancer care during active phases of the
COVID-19 pandemic are discussed separately. (See "COVID-19: Cancer treatment in uninfected
patients during the pandemic, issues related to telemedicine, and resource allocation" and
"COVID-19: Cancer screening, diagnosis, post-treatment surveillance in uninfected patients
during the pandemic, and issues related to COVID-19 vaccination in cancer patients" and
"COVID-19: Risks for infection, clinical presentation, testing, and approach to infected patients
with cancer".)
SOCIETY GUIDELINE LINKS
Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately. (See "Society guideline links: Hepatocellular
carcinoma".)
INFORMATION FOR PATIENTS
UpToDate offers two types of patient education materials, "The Basics" and "Beyond the
Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th
grade reading level, and they answer the four or five key questions a patient might have about
a given condition. These articles are best for patients who want a general overview and who
prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer,
more sophisticated, and more detailed. These articles are written at the 10th to 12th grade
reading level and are best for patients who want in-depth information and are comfortable
with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education articles on
a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
● Basics topic (see "Patient education: Liver cancer (The Basics)")
SUMMARY AND RECOMMENDATIONS
● Hepatocellular carcinoma (HCC) is a tumor with highly variable biology that often occurs
in the setting of chronic liver disease and cirrhosis. A majority of patients with HCC have
underlying liver disease and need comprehensive multidisciplinary care for proper
monitoring and assessment of their disease. (See 'Introduction' above and 'Treatment
algorithms for HCC' above and 'Importance of comprehensive multidisciplinary care'
above.)
● The preoperative evaluation for resection of HCC focuses on the likelihood of disease
being confined to the liver and whether the size and location of the tumor and the
patient's underlying liver function will permit resection. The volume and function of
residual liver remnant should be assessed by hepatic volumetry prior to major resection.
(See 'Preoperative assessment' above and 'Assessment of hepatic reserve' above.)
● Anatomic delineation of tumor extent is best achieved with dynamic multiphase

computed tomography (CT), in which the nonenhanced, hepatic arterial, and portal
venous phases are assessed separately, or with magnetic resonance (MRI) scanning. (See
'Determining the extent of tumor involvement' above.)
● Preoperative portal vein embolization (PVE) is a valuable adjunct to major liver resection
for HCC. PVE can initiate hypertrophy of the anticipated future liver remnant to enable an
extended resection that would otherwise leave a remnant liver insufficient to support life
following partial hepatectomy. Evidence that transarterial chemoembolization (TACE)
should be combined with PVE prior to major right resection is growing. (See 'Portal vein
embolization' above.)
● Curative hepatectomy for HCC can be accomplished by anatomic resection, but

nonanatomic resection may be necessary to minimize the loss of functioning
parenchyma in patients with cirrhosis. In noncirrhotic patients, up to two-thirds of
functional parenchyma can be removed safely, whereas resection is generally limited to
<25 percent of the functional parenchyma in patients with cirrhosis. Minimally invasive
liver resection for HCC in the hands of experienced surgeons is safe and has become the
preferred approach for small HCC in many centers. However, many surgeons await larger
studies with longer follow-up before fully shifting to minimally invasive surgery. (See
'Hepatic resection' above.)
● Most deaths following resection of HCC are due to postoperative liver failure; cirrhosis is
the most important predictor of postresection liver failure and death. However, with
proper patient selection, preparation, and attention to liver remnant volume and
functional reserve, perioperative morbidity and mortality for resection of hepatocellular
carcinoma should be low overall, even among patients with cirrhosis. (See 'Postoperative
morbidity and mortality' above.)
Use of UpToDate is subject to the Subscription and License Agreement.
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Topic 2488 Version 35.0


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11/29/21, 11:00 PM Surgical management of potentially resectable hepatocellular carcinoma - UpToDate

● (See "Epidemiology and risk factors for hepatocellular carcinoma".)

https://www.uptodate.com.asmphlibrary.remotexs.co/contents/surgical-management-of-potentially-resectable-hepatocellular-carcinoma?search=extended hepatecto… 1/28

● (See "Nonsurgical therapies for localized hepatocellular carcinoma: Radiofrequency

TREATMENT ALGORITHMS FOR HCC

A general approach to treatment to hepatocellular carcinoma (HCC) is shown in the figure (

IMPORTANCE OF COMPREHENSIVE MULTIDISCIPLINARY CARE

https://www.uptodate.com.asmphlibrary.remotexs.co/contents/surgical-management-of-potentially-resectable-hepatocellular-carcinoma?search=extended hepatecto… 2/28

Determining the extent of tumor involvement — Anatomic delineation of tumor extent is

https://www.uptodate.com.asmphlibrary.remotexs.co/contents/surgical-management-of-potentially-resectable-hepatocellular-carcinoma?search=extended hepatecto… 3/28

https://www.uptodate.com.asmphlibrary.remotexs.co/contents/surgical-management-of-potentially-resectable-hepatocellular-carcinoma?search=extended hepatecto… 4/28

• In another multicenter retrospective review of 1115 patients with HCC, major

● Multifocality increases the T classification ( table 3) and is associated with lower

https://www.uptodate.com.asmphlibrary.remotexs.co/contents/surgical-management-of-potentially-resectable-hepatocellular-carcinoma?search=extended hepatecto… 6/28

and "Epidemiology, clinical manifestations, diagnosis, and treatment of fibrolamellar

● Approximately 10 percent of HCCs spontaneously rupture. The clinical picture is that of

Although the presence of a tumor rupture suggests a high likelihood of peritoneal

patients, should be low [62]. However, only approximately 5 to 15 percent of patients

Increasingly, functional analyses in conjunction with CT volumetry are gaining acceptance

Portal vein embolization — Preoperative portal vein embolization (PVE) is a valuable adjunct

https://www.uptodate.com.asmphlibrary.remotexs.co/contents/surgical-management-of-potentially-resectable-hepatocellular-carcinoma?search=extended hepatecto… 8/28

Transarterial chemoembolization (TACE) has been proposed as a complementary procedure

Anatomic versus nonanatomic resection — Anatomic resection of the liver is performed by

Nonanatomic resection may be necessary to minimize the loss of functioning parenchyma in

No touch technique — Some surgeons have advocated an anterior or "no touch" technique

https://www.uptodate.com.asmphlibrary.remotexs.co/contents/surgical-management-of-potentially-resectable-hepatocellular-carcinoma?search=extended hepatecto… 10/28

Central hepatic resection — Surgical management of centrally located HCCs (ie, those in

https://www.uptodate.com.asmphlibrary.remotexs.co/contents/surgical-management-of-potentially-resectable-hepatocellular-carcinoma?search=extended hepatecto… 11/28

Minimally invasive hepatic resection — The success of minimally invasive resection of

● In a 2017 meta-analysis of 44 studies including over 5000 patients, laparoscopic liver

POSTOPERATIVE MORBIDITY AND MORTALITY

https://www.uptodate.com.asmphlibrary.remotexs.co/contents/surgical-management-of-potentially-resectable-hepatocellular-carcinoma?search=extended hepatecto… 12/28

POST-TREATMENT SURVEILLANCE AND LONG-TERM OUTCOMES

https://www.uptodate.com.asmphlibrary.remotexs.co/contents/surgical-management-of-potentially-resectable-hepatocellular-carcinoma?search=extended hepatecto… 13/28

posttreatment surveillance" and "Staging and prognostic factors in hepatocellular

SPECIAL CONSIDERATIONS DURING THE COVID-19 PANDEMIC

SOCIETY GUIDELINE LINKS

INFORMATION FOR PATIENTS

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● Basics topic (see "Patient education: Liver cancer (The Basics)")

SUMMARY AND RECOMMENDATIONS

● Anatomic delineation of tumor extent is best achieved with dynamic multiphase

● Curative hepatectomy for HCC can be accomplished by anatomic resection, but

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3. Berkan-Kawińska A, Piekarska A. Hepatocellular carcinoma in non-alcohol fatty liver

4. Okuno M, Newhook TE, Joechle K, et al. Characteristics of atypical large well-

7. Bruix J. Treatment of hepatocellular carcinoma. Hepatology 1997; 25:259.

https://www.uptodate.com.asmphlibrary.remotexs.co/contents/surgical-management-of-potentially-resectable-hepatocellular-carcinoma?search=extended hepatecto… 16/28

9. Bruix J, Castells A, Bosch J, et al. Surgical resection of hepatocellular carcinoma in

11. Roayaie S, Jibara G, Taouli B, Schwartz M. Resection of hepatocellular carcinoma with

14. Minagawa M, Ikai I, Matsuyama Y, et al. Staging of hepatocellular carcinoma: assessment

17. Iannaccone R, Laghi A, Catalano C, et al. Hepatocellular carcinoma: role of unenhanced

https://www.uptodate.com.asmphlibrary.remotexs.co/contents/surgical-management-of-potentially-resectable-hepatocellular-carcinoma?search=extended hepatecto… 17/28

https://www.uptodate.com.asmphlibrary.remotexs.co/contents/surgical-management-of-potentially-resectable-hepatocellular-carcinoma?search=extended hepatecto… 18/28

32. Hanazaki K, Kajikawa S, Shimozawa N, et al. Hepatic resection for hepatocellular

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51. Recordare A, Bonariol L, Caratozzolo E, et al. Management of spontaneous bleeding due

https://www.uptodate.com.asmphlibrary.remotexs.co/contents/surgical-management-of-potentially-resectable-hepatocellular-carcinoma?search=extended hepatecto… 20/28

57. Takebayashi T, Kondo S, Ambo Y, et al. Staged hepatectomy following arterial

77. Sasaki A, Iwashita Y, Shibata K, et al. Preoperative transcatheter arterial

80. Harada T, Matsuo K, Inoue T, et al. Is preoperative hepatic arterial chemoembolization

https://www.uptodate.com.asmphlibrary.remotexs.co/contents/surgical-management-of-potentially-resectable-hepatocellular-carcinoma?search=extended hepatecto… 22/28