and autopsy series estimated that FNH occurs in 4% to 8% of individuals, with a strong predilection for

women aged 20 to 50 years.43 Unlike the origin of hemangioma or hepatocellular adenoma, the origin

of FNH is thought to be due to hyperplastic growth of normal hepatocytes with a malformed biliary

draining system or a hyperplastic response to a pre-existing arteriovenous malformation. FNH does not

contain a portal venous supply.

Figure 60-6. Nodular enhancement typically observed in hemangioma in dynamic CT. The mass is gradually enhanced from the

peripheral part to the central part of the lesion.

Figure 60-7. Typical dynamic CT image of focal nodular hyperplasia. The lesion is homogeneously enhanced in the arterial phase

with central hypodensity area suggestive of a central scar (left). The mass becomes isodense in the portal phase (right).

In plain CT, the lesion is isoattenuated with normal liver and may exhibit the characteristic

hypoattenuated central scar. With contrast in the arterial phase, FNHs enhance brightly and become

again isoattenuated to adjacent parenchyma in the portal phase (Fig. 60-7). The central scar may

enhance on delayed phases. MRI reveals a similar dynamic enhancement pattern: FNHs appear

isointense on T1-weighted images and hyperintense on T2-weighted sequences. With gadolinium

enhancement, the lesion is homogeneously enhanced in the arterial phase and the central scar becomes

hypointense in the delayed phase.

The majority of FNHs is asymptomatic and found incidentally on abdominal imaging for other

indications. Because of the benign nature of FNHs and the very low risk of spontaneous rupture,

treatment should be reserved for patients with persistent symptoms not explained by another problem.

1552

Hepatic Adenoma

Hepatic adenoma (HA) is a rare benign tumor with an estimated prevalence of approximately 1% on

postmortem examinations.52 Typically, HAs occur in women of child-bearing age who often have a

history of long-term use of oral contraceptives. In the majority of the cases, HA lesions are solitary and

asymptomatic. However, the presence of multiple nodules (typically >10 nodules) indicates a distinct

entity called hepatic adenomatosis, which has a different implication for treatment.53

Adenomas are well-circumscribed lesions that contain sheets of hepatocytes without intervening

biliary ductules or portal tracts. Conventionally, HA was considered to have variable imaging

characteristics and was described as a heterogeneous hypervascular mass with areas of fat, hemorrhage,

and necrosis on multiphase CT or MRI.54 With the introduction of the new phenotype–genotype

classification of HA, however, correlation between the imaging characteristics and different subtypes

has been reported.55,56 HAs are grouped into 1 of 4 subtypes. HA-H (HNF1A-mutated hepatic adenoma)

is the most frequently occurring one (35% to 40%), presenting steatosis and absence of inflammatory

infiltrate or cytologic atypia. This subtype is frequently associated with somatic mutation of the TCF1

(HNF1A) gene or heterozygous germline mutations of the CYP1B1 gene. HA-B (β-catenin–mutated

hepatic adenoma, 15% to 19%) is morphologically characterized by pseudoacinar formation and mild

cytologic atypia. Steatosis is rare and inflammation is absent in this subtype. β-Catenin gene-activating

mutations are frequently observed in this subtype. HA-I (inflammatory hepatic adenoma, 30% to 35%)

exhibits pseudoportal tracts that lack veins and bile ducts and contain large, thick-walled arteries

surrounded by fibroconnective tissue with variable ductular reaction and inflammation. The last

subtype, HA-U (10%), is associated with gain-of-function mutations of the IL6ST gene. These HAs lack

distinctive morphologic and molecular features.

Patients with HAs appear to have a risk of either rupture or malignant transformation (estimated risk

of 4.2% to 4.5%57,58), which is different from the other benign lesions. The HA-B subtype has been

found to be more frequently associated with the development of HCC.59,60 For small lesions (<5 cm),

some experts have recommended withdrawal of oral contraceptives in the expectation of tumor

regression.61,62 However, regression of HA upon cessation of oral contraceptives does not remove the

risk of malignant transformation in women.63 High-risk groups for malignant transformation include

male patients, patients with a history of androgenic or anabolic steroid intake, and patients with

glycogen storage disease.

The potential for malignant transformation and the risk of hemorrhage drive active surgical

interventions for large HAs. Surgical resection is recommended for HAs >5 cm, those with intratumoral

hemorrhage, and those that increase in size.64–67 HAs are hypervascular tumors and are sometimes

difficult to distinguish from HCC. Typically, HAs are represented by bright enhancement in the arterial

phase and iso- to hypodensity in the portal phase (Fig. 60-8). With MRI, HAs are visualized as welldefined lesions with isointense or hyperintense features on T1- and T2-weighted images, depending on

the fat content. Similar to dynamic CT, gadolinium enhancement shows marked enhancement in the

arterial phase and isointensity in the portal phase.

PRIMARY HEPATIC MALIGNANCIES

Hepatocellular Carcinoma

Primary liver cancer is one of the most common solid tumors and the second-leading cause of cancerrelated deaths worldwide.68 Despite recent developments in preventing and treating viral hepatitis,

nearly 750,000 deaths were reported in 2012 for patients with primary liver cancer. Among these cases,

HCC is the most common type of hepatic malignancy. There is wide geographic variability in incidence,

with the majority of the cases occurring in developing countries compared with developed countries.

China alone accounts for more than half of the new cases of liver cancer; other high-incidence areas are

sub-Saharan Africa, Japan, and Southeast Asia, where viral hepatitis or aflatoxin exposure is more

endemic. In the United States, the incidence of HCC is increasing the second-fastest of all tumor types,

probably due primarily to the HCV epidemic.69 There is also global variation in the risk factors for HCC.

HBV and HCV infections are the leading causes of HCC, accounting for 75% of the cases worldwide.70

HBV infection is more common except in Japan, where HCV infection is the most common cause of

HCC. Alcoholic liver disease accounts for a significant proportion of HCC in the Western countries.

Aflatoxin exposure is also an important risk factor in China and sub-Saharan Africa.

1553

Figure 60-8. A huge hepatic adenoma found in a 31-year-old woman. Dynamic CT revealed early enhancement in the arterial

phase (left) and iso- to hypodensity in the portal phase (right). This patient had no underlying liver disease and both serum alphafetoprotein level and plasma des-gamma-carboxyprothrombin level were within normal limits.

Screening measures for HCC have been assessed in various studies, which primarily focus on the roles

of serum AFP level and ultrasound. The American Association for the Study of Liver Disease (AASLD)

has created guidelines regarding the use of these screening techniques based on the best existing

evidence.20 The AASLD currently recommends serial hepatic ultrasonography and serum AFP

measurement every 6 to 12 months for at-risk populations (e.g., any patient with cirrhosis). Similarly,

the Japanese Society of Hepatology has recommended hepatic ultrasonography and serum AFP or

plasma DCP measurement every 3 to 4 months and dynamic CT or MRI every 6 to 12 months for veryhigh-risk populations (e.g., those with HBV- or HCV-related cirrhosis), and hepatic ultrasonography and

assessment for tumor markers every 6 months for high-risk populations (e.g., HBV- or HCV-related

chronic hepatitis, or cirrhosis with other etiologies) with or without dynamic CT or MRI every 6 to 12

months, as appropriate.71 A randomized controlled trial from China reported that the use of ultrasound

and AFP enables early detection of HCC and lowers HCC-related mortality by 37% in patients with HBV

infection.72 Various nonrandomized studies have confirmed prognostic improvement through regular

surveillance programs among patients at high risk of HCC.73–75 Regarding the interval of screening, a

recent meta-analysis revealed that surveillance every 6 months is significantly better than screening

every 12 months for the early detection of HCC. Santi et al.76 reported that 70% of newly diagnosed

HCCs fell within the Milan criteria (solitary tumor ≤5 cm or ≤3 tumors with each tumor ≤3 cm)77

when screening occurred at least every 6 months, while the proportion of HCCs that fell within the

Milan criteria was 57% and the overall survival rate was inferior with surveillance every 6 to 12

months. When a suspected nodule is detected during regular screening, a contrast-enhanced three-phase

CT or MRI is needed. Because HCCs are fed mainly by arterial flow, early enhancement and washout of

contrast on the delayed phase of the scan are typical findings suggestive of HCC (Fig. 60-9). These

enhancement characteristics increase the specificity of the scan to >95%.78

4 The choice of therapy is individualized based on the tumor burden, degree of underlying liver

disease, patient performance status, and overall possibility of side effects or complications balanced

with acceptable results. The Barcelona Clinic Liver Cancer (BCLC) staging system79 is widely used to

stratify patients for specific therapies (Algorithm 60-1). However, the limitation of the BCLC algorithm

is that it is fairly conservative with regard to the application of surgical therapy. Patients with larger

solitary tumors are not considered surgical candidates despite growing experience with resection with

acceptable outcomes in this group.80,81 In the guidelines on liver cancer treatment proposed by the

Japan Society of Hepatology,22 surgical resection is indicated for CTP class A or class B patients with

HCCs with up to three nodules irrespective of the size of each tumor, while liver transplantation is

limited to CTP class C patients meeting the Milan criteria.

For HCC patients undergoing liver resection, strict assessment of the hepatic functional reserve is

important because HCC usually develops in an injured liver and, accordingly, the maximum extent of

resection must be estimated carefully. Functional investigations have been proposed to better evaluate

the severity of chronic liver disease. Measurement of indocyanine green (ICG) retention rate at 15

minutes (ICG-R15) is the most frequently used test. For patients with obstructive jaundice or congenital

intolerance to ICG, 99mTc-galactosyl human serum albumin (GSA) scintigraphy sensitively estimates the

hepatic functional reserve. Algorithm 60-2 shows a decision tree used for surgical planning according to

1554

the individual hepatic functional reserve (Makuuchi criteria).82 By strictly following this algorithm, no

mortality due to hepatic insufficiency was reported in the University of Tokyo series.1

Figure 60-9. Typical enhancement pattern of HCC with early enhancement in the arterial phase (left) and washout in the portal

phase (right).

Because HCC tends to spread via portal veins, anatomic resection of the tumor-bearing portal

territory is a theoretically reasonable approach (Fig. 60-10). Although the efficacy of anatomic resection

remains controversial, various studies have reported prognostic superiority of anatomic resection with

an apparent lower local recurrence rate and a higher recurrence-free survival rate compared to

nonanatomic limited resection of the liver.83–85 Liver transplantation is another surgical approach with a

theoretically higher chance of eradicating the tumor burden, especially for patients with severe hepatic

dysfunction. Clinical outcomes of liver transplantation for HCC were initially poor in the early era.

However, after the landmark study by Mazzaferro et al.,77 good survival outcomes are expected in

select HCC patients with tumors of limited size and a small number of nodules (Milan criteria). The

selection criterion for transplantation used by Mazzaferro et al.77 was a tumor diameter of ≤5 cm in

patients with a single HCC or ≤3 cm in patients with 2 or 3 lesions. This criterion has since been

extended with or without tumor markers or biopsy findings in several high-volume transplant centers

(Table 60-2).86–97

Algorithm 60-1. BCLC algorithm for treatment selection in patients with HCC. (Adapted from Llovet JM, Burroughs A, Bruix J.

Hepatocellular carcinoma. Lancet 2003;362:1907–1917 with permission.)

1555

Algorithm 60-2. Treatment algorithm of patients with hepatocellular carcinoma (HCC) based on serum bilirubin level and

indocyanine green retention rate at 15 minutes. (Adapted from Makuuchi Kosuge T, Takayama T, et al. Surgery for small liver

cancers. Semin Surg Oncol 1993;9:298–304 with permission.)

Intrahepatic Cholangiocarcinoma

Intrahepatic cholangiocarcinoma (ICC) is a relatively uncommon disease, accounting for 5% to 30% of

all primary liver malignancies.98 In the United States, the age-adjusted incidence of ICC increased from

0.32 in 1975 to 0.85 per 100,000 population in 2000 and has yet to plateau.99 The overall 5-year

survival rate for patients with unresectable tumor is dismal: 5% to 10%. Because systemic therapy for

ICC has not yet been established, surgical resection offers the only chance for cure. However, the

overall 5-year survival rate after curative-intent surgery is disappointing at 20% to 35%.100

Figure 60-10. Theoretical concept of anatomic resection for HCC. This schema shows an example of resection for HCC located in

the ventral part of Segment VIII. The dashed line A-A’ indicates nonanatomic limited resection with adequate surgical margin and

the dotted line B-B’ represents anatomic resection of the ventral part of Segment VIII. Because the “tumor-bearing” portal territory is

at high risk of harboring micrometastases scattered via portal veins (arrows), systematic removal of the corresponding portal region

would offer a better chance of eradicating the cancer cells. With systematic removal of the territory of the ventral branch of

Segment VIII, the tumor-bearing portal territory, which is at high risk of micrometastases, can be resected. T, tumor; P8v, ventral

branch of Segment VIII portal pedicle; P8d, dorsal branch of Segment VIII portal pedicle; MHV, middle hepatic vein; V8i,

intermediate vein for Segment VIII.

ICC is thought to derive from a common hepatic progenitor cell that may also give rise to HCC,101

and combined hepatocellular-cholangiocarcinoma having histopathologic features of both HCC and ICC

is sometimes observed. Risk factors for ICC have not yet been established, although chronic liver

disease and cirrhosis are reportedly correlated with ICC. On dynamic imaging studies, ICC is not

enhanced due to the hypovascular nature of this tumor type. However, various degrees of ring

enhancement are observed surrounding the lesion, reflecting the fibrous connective tissue frequently

observed around the tumor. In laboratory tests, elevated carcinoembryonic antigen or CA19-9 in

primary solid liver lesion is suggestive of ICC.

A recent meta-analysis showed that factors associated with shorter overall survival included older

patient age, larger tumor size, multiple tumors, lymph node metastasis, vascular invasion, and poor

tumor differentiation. Because up to 30% of patients have lymph node metastases, routine

lymphadenectomy is recommended,102 although the survival benefit remains controversial.

METASTATIC LIVER TUMORS

1556

 

sensitivity is usually associated with reduced specificity. Limitations of 18F-FDG-PET include its limited

availability, high cost, limited access to specialized techniques, and lack of expertise to interpret the

results. Therefore, from a practical clinical perspective, CT, MRI, or both should be the first-line

modalities for characterizing hepatic lesions and 18F-FDG-PET can be used as the second-line modality

for evaluating the metabolic features of the lesion or the presence of extrahepatic disease. Ultrasound

should be used as a routine diagnostic tool throughout the perioperative period. It is mandatory for

hepatobiliary surgeons to acquire expertise in ultrasonography.

Figure 60-1. Couinaud segmental anatomy of the liver. In Couinaud theory, the liver is divided in to two hemilivers, four sectors,

and eight segments according to the portal venous ramification pattern. Three major hepatic veins represent the posit

sensitivity is usually associated with reduced specificity. Limitations of 18F-FDG-PET include its limited

availability, high cost, limited access to specialized techniques, and lack of expertise to interpret the

results. Therefore, from a practical clinical perspective, CT, MRI, or both should be the first-line

modalities for characterizing hepatic lesions and 18F-FDG-PET can be used as the second-line modality

for evaluating the metabolic features of the lesion or the presence of extrahepatic disease. Ultrasound

should be used as a routine diagnostic tool throughout the perioperative period. It is mandatory for

hepatobiliary surgeons to acquire expertise in ultrasonography.

Figure 60-1. Couinaud segmental anatomy of the liver. In Couinaud theory, the liver is divided in to two hemilivers, four sectors,

and eight segments according to the portal venous ramification pattern. Three major hepatic veins represent the position of

intersectoral plane (called scissura). LHV, left hepatic vein; MHV, middle hepatic vein; RHV, right hepatic vein.

1548

Figure 60-2. Three-dimensional shape of the intersegmental plane. Top left: Lateral view of the right hemiliver. The right lateral

sector indicated by the dark-gray color and an interdigitated demarcation line is visible on the liver surface (white dotted line).

Segment VIII (S8) protrudes dorsolaterally (arrows) relative to Segment V (S5). Top right: Dorsolateral view of the cut surface after

a simulated right lateral sectorectomy. The right scissure exhibits a concave shape because of the protrusion of Segment VIII (H,

head; L, left; P, posterior). Axial computed tomographic image (bottom left) and diagram (bottom right) illustrating that the

intersegmental border between Segments VIII and VII is not compatible with the plane of the right hepatic vein. The posterolateral

part of the right hepatic vein in Segment VIII is presented. (Adapted from Shindoh J, Mise Y, Satou S, et al. The intersegmental

plane of the liver is not always flat–tricks for anatomical liver resection. Ann Surg 2010;251(5):917–922.)

In radiographic evaluation, the tumor location is described according to Couinaud anatomy for liver

segments.35 In Couinaud theory, the liver can be divided into two hemilivers, four sectors, and eight

segments defined as the territories of the first-, second-, and third-order portal branches, respectively

(Fig. 60-1). Because typical systematic surgical resection follows the segmental anatomy of the liver,

the location of tumor should be defined based on accurate understanding of the segmental anatomy of

the liver. “Segment” is defined as a territory of a portal branch and its actual three-dimensional shape is

not simple, despite depictions in many surgical textbooks.36 For example, Segment VIII usually

protrudes craniolaterally, overhanging the right hepatic vein (Fig. 60-2). Accordingly, a hepatic lesion

located just to the cranial side or posterolateral side of the right hepatic vein is a Segment VIII tumor,

which can be easily confirmed by tracking the nearest portal branches on CT images.

BENIGN HEPATIC NEOPLASMS

Cystic Lesions

Simple Cyst

The distinction between solid and cystic lesions is clinically important, as the vast majority of cystic

lesions of the liver are benign in behavior. The majority of the incidentally diagnosed cystic lesions are

simple cysts, which have no malignant potential and rarely become symptomatic. However, surgical

treatment is considered for symptomatic giant cysts stretching the liver capsule or compressing the

adjacent organs. Laparoscopic unroofing (Fig. 60-3) may be the ideal approach for these lesions, which

has acceptably good outcomes and a negligible recurrence rate in experienced hands.37

1549

Figure 60-3. A huge hepatic cyst observed in the right hemiliver (left). Laparoscopic unroofing (right) was performed for this

patient to relieve the abdominal pain associated with distension of the liver capsule. Cystic fluid was first suctioned and then the

anterior wall of the cyst (*) was resected with an energy device. (Images courtesy to Dr. Yasuji Seyama.)

Polycystic Liver Disease

Polycystic liver disease (PLD) is a rare presentation of cystic liver lesions and can be difficult to

manage.38 Approximately 80% to 90% of PLD cases represent an autosomal dominant disease associated

with polycystic kidney disease. In these patients, renal failure frequently occurs due to destruction of

the kidney by multiple cysts. Although patients with PLD rarely develop hepatic failure regardless of

the marked change in the distorted liver on imaging studies (Fig. 60-4), various symptoms caused by

distention of the liver, stretching of the diaphragm, or compression of the adjacent organs require

therapeutic intervention. Treatment for PLD should be performed in a stepwise fashion. Ultrasonically

guided puncture of the cysts should be the first choice to decompress the distended cysts and drain the

fluid. If percutaneous aspiration is not effective, the next option is laparoscopic fenestration of the cysts.

Liver resection or transplantation should be the final treatment option. A limited number of patients

require liver transplantation due to the progressive destruction of liver parenchyma and hepatic

dysfunction. However, liver transplantation for PLD is a challenging procedure due to severe adhesion

and huge liver size, usually causes major bleeding, and requires a large amount of transfusions

especially for patients with a history of multiple interventions or surgery for PLD. A recent report

suggested that a history of open intervention is a strong risk factor for severe postoperative

complications, longer hospital stay, and poor long-term outcomes after transplantation.39 Therefore, a

minimally invasive approach is preferable for disease-directed interventions for PLD as long as this

approach is viable.

Figure 60-4. CT image of a patient with polycystic liver associated with autosomal dominant polycystic kidney disease. The liver is

markedly distended due to destruction of the liver by multiple cysts and compensatory regeneration of hepatic parenchyma.

However, the hepatic function is maintained with an albumin level of 2.8 g/dL, bilirubin level of 1.5 mg/dL, and INR of 1.12,

with slight ascites and no evidence of encephalopathy (Child–Turcotte–Pugh class B).

1550

Biliary Cystadenoma

3 Most hepatic cysts are asymptomatic, and surgical resection is indicated only for lesions for which

there is concern for malignancy or malignant potential. Wall enhancement in contrast-enhanced CT,

serrated or septated wall visualized by ultrasound, or rapid increase in size suggests malignant potential

of a lesion. Biliary cystadenoma is the common cystic lesion with malignant potential, accounting for

5% of all cystic lesions in the liver.40 These lesions arise from the biliary epithelium and typically

present in middle-aged women. Because it is difficult to distinguish between cystadenoma and

cystadenocarcinoma (Fig. 60-5) and because cystadenoma has a propensity toward local recurrence and

malignant degeneration to cystadenocarcinoma,41,42 surgical resection is indicated primarily when

biliary cystadenoma is suspected.

Solid Lesions

Solid lesions should be handled with care because benign lesions are sometimes difficult to discriminate

from malignant tumors.

Figure 60-5. CT image of a cystadenocarcinoma. A multicystic lesion with an enhanced intracystic papillary component was

observed (arrow).

Hemangioma

Hemangioma is the most common benign lesion observed in the liver; the estimated prevalence is 3% to

20%.43 Most hemangiomas are identified in individuals aged 40 to 60 years and appear to be more

common in women, with a female-to-male ratio of 2:1.44 Grossly, hemangiomas are well-circumscribed

and compressible lesions. Histopathologically, multiple blood vessels lined by endothelial cells are

present.45 The majority of hemangiomas are small asymptomatic lesions that can be managed

nonsurgically. Spontaneous or traumatic rupture of hemangioma in exceptional cases has been reported,

but the risk of rupture is considered very low. Therefore, the majority of these cases can be left

untreated with regular follow-up imaging studies.

Accurate radiographic diagnosis of a hepatic hemangioma is important, as establishment of this

diagnosis requires no additional intervention for the majority of patients. For diagnosis, a dynamic

study is the most important for characterizing the hemodynamics in a lesion. Contrast-enhanced CT

demonstrates a typical pattern of nodular enhancement from the periphery with central filling on

delayed images (Fig. 60-6). Contrast-enhanced MRI also shows similar patterns in dynamic studies, and

a very high intensity in T2-weighted images is suggestive of hemangioma. A diagnosis of hemangioma

should be made based on these radiographic findings. Although biopsy is not absolutely contraindicated,

a fatality from uncontrollable bleeding has been reported, so unnecessary biopsy should be avoided.46

Surgical resection is warranted in the setting of abdominal symptoms,47–49 spontaneous rupture,50

rapid growth of the lesion,51 or coagulopathy due to Kasabach–Merritt syndrome. Elective surgical

treatment is accomplished by either enucleation or formal hepatic resection. Enucleation is often easily

performed because hemangiomas are exophytic to some degree and a pseudocapsular plane can be

developed efficiently. Hemangiomas typically have limited outflow and the internal pressure may be

high. Early ligation of the feeding arteries, especially in patients with large hemangiomas, is a key

point, as the size reduction caused by the decompression is technically beneficial for surgical

manipulation and resection.

Focal Nodular Hyperplasia

Focal nodular hyperplasia (FNH) is the second most common benign neoplasm of the liver. A clinical

1551

 

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1544

Chapter 60

Hepatic Neoplasms

Junichi Shindoh and Jean-Nicolas Vauthey

Key Points

1 Given the increasing complexity in the field of liver surgery, the surgical indications for hepatic

neoplasms should be determined by a multidisciplinary team, including hepatobiliary surgeons, to

optimize the treatment approach and adequate timing of surgery for patients who would benefit

from hepatic resection.

2 Child–Turcotte–Pugh (CTP) classification describes the overall status of the hepatic functional

reserve and the risk of treatment. Surgical resection is generally indicated for CTP class A or highly

selected CTP class B patients, whereas CTP class C is a contraindication for hepatic resection.

3 Surgical therapy of benign hepatic neoplasms should be confined to symptomatic patients or those

with a risk of malignant transformation (e.g., biliary cystadenoma, hepatic adenoma [HA]).

4 The choice of therapy for HCC should be individualized based on the tumor burden, degree of

underlying liver disease, patient performance status, and overall possibility of side effects or

complications balanced with acceptable clinical results.

5 Complete resection of colorectal liver metastases (CLM) is associated with an improved 5-year

survival rate of up to 58%. Adequate assessment and preoperative management are essential in

selecting patients with resectable or potentially resectable CLM.

6 For surgical planning, precise anatomic interpretation of the intrahepatic vascular structures is

needed. Three-dimensional liver simulation techniques have recently been introduced which enable

easy access to anatomic information and help with adequate surgical planning.

7 Portal vein embolization (PVE) is a safe and minimally invasive procedure to increase the size of the

future liver remnant (FLR) and decrease the surgical risk of extended hepatectomies. Failure to

respond to PVE is associated with postoperative hepatic insufficiency and mortality due to liver

failure.

8 Adequate exposure of the surgical field and control of bleeding during hepatic parenchymal

transection are basic requirements for safe liver surgery. Liver surgeons should be familiar with

techniques for safe handling of the liver.

9 Laparoscopic liver resection has been recognized as a feasible and safe procedure for selected

patients undergoing minor resections, and this approach has recently been expanded to major

hepatectomies. The indication for the laparoscopic approach should be determined by considering

the technical feasibility, the surgeon’s surgical skill, and the oncologic curability of the procedure.

INTRODUCTION

The management of hepatic neoplasms is an increasingly complex and multidisciplinary area of surgery.

With advances in surgical technique and perioperative care, the safety of liver resection has

dramatically improved over the decades and the mortality rate after major hepatectomy has recently

been reported to be <5% at high-volume hepatobiliary centers.1,2

Liver resection and liver transplantation are widely accepted as curative surgical options for selected

hepatic neoplasms. Surgical treatment for hepatic neoplasms requires the balancing of two conflicting

factors, oncologic curability and surgical safety. The size of the future liver remnant (FLR) affects

mortality and morbidity after liver resection, and the chance of cure is often linked to the extent of

resection.3,4 Therefore, the surgical indication should be determined based on the balance of surgical

curability and extent of liver resection, especially for patients who have impaired hepatic functional due

to underlying chronic liver disease. In this chapter, we review the basic principles of surgical

management and appropriate surgical techniques for hepatic neoplasms.

1545

PRIMARY ASSESSMENTS FOR TREATMENT SELECTION

Overview

When a hepatic neoplasm is found, the initial diagnostic steps should include (1) precise anatomic

description of the hepatic lesion (size, number, location, and relation to intrahepatic vascular

structures), (2) evaluation of the hepatic functional reserve in the underlying liver, and (3) assessment

of the oncologic feature of the lesion in question.

The initial treatment is selected based on the information obtained from these primary assessments.

When surgical management is considered, further workup is needed to determine or optimize the

surgical indication through (1) detailed anatomic assessment and (2) systematic volumetry of FLR to

stratify the risk of postoperative hepatic insufficiency and mortality from liver failure. If the estimated

FLR is too small according to the hepatic functional reserve of an individual patient, portal vein

embolization (PVE) or a two-stage approach5,6 is considered in combination with local or systemic

therapy, as appropriate.

1 Given the increasing complexity in this field of surgery, the surgical indication should be

determined by a multidisciplinary team, including hepatobiliary surgeons. In the era of effective

chemotherapy and various radiologic interventions, the surgical indication can change during the initial

nonsurgical treatment even in patients with initially unresectable hepatic lesions. Because only surgical

resection offers a chance of cure for patients with advanced hepatic malignancies, a multidisciplinary

approach is important to identify patients who would benefit from surgery and to optimize overall

treatment outcomes.

Screening for Underlying Liver Disease

Assessment of a patient with a new diagnosis of a hepatic neoplasm should begin with consideration of

any underlying chronic liver disease. Viral hepatitis is the most common cause of chronic liver disease

and primary liver cancer, affecting 240 million people with hepatitis B (HCB) and 130 to 150 million

people with hepatitis C (HCV) worldwide – most of whom are unaware of their disease.7 Thus, routine

screening of viral hepatitis is mandatory for patients with hepatic neoplasms. The number of serologynegative patients with primary liver cancers is increasing, and alcoholic liver disease and nonalcoholic

liver disease are the next leading causes of chronic liver disease. Both are characterized by histologic

alterations, including steatosis, and each can lead to cirrhosis and primary liver cancer.8,9 Careful

history taking is important primarily to specify the risk of fatty liver disease, such as those due to

obesity, alcohol abuse, diabetes mellitus, and metabolic syndrome. In addition, cholestatic liver disease

is an important etiology for chronic liver disease because it is a common cause of decompensated

cirrhosis requiring liver transplantation. Primary sclerosing cholangitis is a strong risk factor for

cholangiocarcinoma and cases of end-stage primary sclerosing cholangitis are frequently complicated

with malignant biliary stricture, which may be difficult to distinguish from benign biliary strictures.

Finally, a history of systemic therapy for hepatic malignancy is an increasingly important factor in the

era of effective chemotherapy. Several studies have confirmed that prolonged systemic therapy is

associated with regimen-specific histopathologic injury of the liver10–12 and decreased hepatic functional

reserve.12–15 Therefore, risk assessment of chemotherapy-induced liver injury is also necessary,

especially for patients with colorectal liver metastases (CLM) for whom systemic treatment has been

used.

Laboratory Tests

A comprehensive metabolic panel, a complete blood count, and measurement of coagulation parameters

are essential for potential candidates for surgery. The basic functional status of the liver can be

evaluated by serum albumin concentration, bilirubin concentration, and transaminase level. The renal

function is also important because advanced liver disease is frequently compromised with renal

dysfunction and impaired renal function is correlated with poor prognosis. Regarding the complete

blood count, attention should be paid to platelet count. Thrombocytopenia is reportedly correlated with

the degree of fibrosis in the underlying liver, and thrombocytopenia suggests the presence of

hypersplenism and portal hypertension, which are associated with increased need for treatment. Among

the coagulation parameters, prothrombin time is the most sensitive indicator of synthetic function of the

liver. Because prothrombin time represents the activity of rapid-turnover proteins synthesized

exclusively in the liver, prolonged prothrombin time indicates functional impairment of the liver in a

real-time fashion.

1546

Measurement of tumor markers specific to hepatic malignancies helps the diagnostic process for

hepatic neoplasms. For hepatocellular carcinoma (HCC), serum alpha-fetoprotein (AFP) level,

proportion of Lens-culinaris agglutinin-reactive fraction of AFP, and plasma des-gammacarboxyprothrombin (DCP) level have been reported to be useful for both diagnosing and predicting

surgical outcomes.16 Recent studies have reported that these markers are also predictive for

posttransplant recurrence of HCC.17–19 For the other hepatic neoplasms, serum levels of

carcinoembryonic antigen and CA19-9 are usually screened to evaluate the malignant potential of the

lesions.

Stratification of Overall Status of the Hepatic Functional Reserve

2 For selection of treatment, the overall status of the hepatic functional reserve and the risk of

treatment are stratified by the Child–Turcotte–Pugh (CTP) score, which is calculated using the presence

of encephalopathy, presence of ascites, serum bilirubin concentration, serum albumin concentration, and

prothrombin time (Table 60-1). The CTP score is now included in various treatment algorithms for

hepatic neoplasms,20–22 and liver resection is usually indicated for CTP class A patients or highly

selected patients classified as CTP class B. The consensus is that CTP class C patients should not undergo

surgical resection due to a high perioperative mortality rate.21 In the field of liver transplantation, the

Model for End-Stage Liver Disease (MELD) score has recently been used as a more sensitive parameter

for transplant allocation because of its accuracy in predicting patient mortality on waiting lists.23,24

Although its suitability and application for liver resection remains debatable,25,26 the MELD score

reportedly predicts posttransplant outcomes through optimizing transplant allocation.27,28

Table 60-1 Child–Turcotte–Pugh (CTP) Classification

Imaging Studies

Adequate imaging is essential for diagnosis, staging, treatment planning, and evaluation of the response

to chemotherapy of hepatic neoplasms. Computed tomography (CT) and magnetic resonance imaging

(MRI) are the most common modalities used for diagnosing and evaluating patients with liver lesions.

CT plays a central role in characterizing hepatic neoplasms because of its accessibility, practicality, low

cost, and acceptable sensitivity and specificity. For diagnosis and adequate evaluation of tumor burden,

dynamic contrast enhancement with a liver-specific protocol is necessary to characterize the vascularity

and extension of the tumor. MRI combining gadolinium ethoxybenzyl diethylenetriamine pentaacetic

acid (Gd-EOB-DTPA) delayed imaging and diffusion-weighted imaging provides the best performance

for detecting and characterizing liver lesions, particularly those <10 mm in size.29 Ultrasound is

another important modality that is used both for preoperative diagnosis and postoperative follow-up.

Although its sensitivity is inferior to CT and MRI, the advantages of ultrasound are that it is accessible

and less invasive than the other diagnostic modalities. Contrast-enhanced ultrasound using the secondgeneration contrast medium perflubutane (Sonazoid) enables evaluation of vascularity and clear

visualization of malignant lesions as areas lacking Kupffer cells. Furthermore, intraoperative application

of this agent improves the diagnostic value of ultrasound and the curability of surgery.30,31 18Ffluorodeoxyglucose positron emission topography (18F-FDG-PET) may be a powerful adjunct to other

liver imaging techniques in selected patients. Niekel et al.32 reviewed 39 articles (3,391 patients) and

showed that the estimated sensitivities to detecting CLM on a per-lesion basis for CT, MRI, and 18F-FDGPET were 74.4%, 80.3%, and 81.4%, respectively. In addition, the usefulness of 18F-FDG-PET has been

reported especially for detecting extrahepatic metastases or local recurrence.33,34 However, increased

1547

 

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Figure 59-16. LeVeen peritoneovenous shunt used for routing ascitic fluid into the systemic circulation. The shunt consists of

fenestrated tubing for insertion into the peritoneal cavity, a one-way valve, and a length of venous tubing for insertion into the

superior vena cava.

12 Spontaneous bacterial peritonitis is a potentially lethal complication of portal hypertension with

ascites that occurs in up to 10% of patients. The cause of spontaneous bacterial peritonitis is unknown.

Antecedent gastrointestinal hemorrhage is common, and spontaneous bacterial peritonitis in this setting

may be related to bacterial translocation from the gut. Deficits in immune function, both systemically

and within the abdomen, including depressed272 reticuloendothelial function,273–275 low ascitic protein

concentration, and deficient ascitic opsonic activity, may play a role. Patients often present with

abdominal pain and fever, but 10% to 20% of cases are discovered on routine paracentesis.276–278 In

addition, patients may present with other signs not clearly related to spontaneous bacterial peritonitis,

including worsening encephalopathy and deteriorating renal function. The diagnosis is easily made by

examination of the ascitic fluid obtained by paracentesis. An elevated number of white blood cells

(>250/mm3) are diagnostic. The vast majority of cases of spontaneous bacterial peritonitis are caused

by a single organism, most commonly gram-negative enteric bacteria. Hematogenous spread may lead

to infection with Streptococcus pneumoniae (Table 59-14). If more than one organism is present, the

diagnosis of spontaneous bacterial peritonitis must be questioned, and a search for intra-abdominal

disease (secondary peritonitis), such as a perforated viscus or diverticulitis, should be performed.

Table 59-14 Bacteriology of Spontaneous Bacterial Peritonitis

1531

The treatment of spontaneous bacterial peritonitis consists of supportive care and broad-spectrum

antibiotics, most commonly cefotaxime, a third-generation cephalosporin. Protein replacement has been

shown to significantly reduce mortality in patients with spontaneous bacterial peritonitis and is

complementary to other interventions as established in the landmark publication from Barcelona.279

Other antibiotics with proven efficacy include ofloxacin, a quinolone. This antibiotic has potent activity

against gram-negative organisms and reaches high levels in ascitic fluid. For patients who are clinically

stable and able to take oral medications, this is the drug of choice. Cure can be achieved in 75% to 90%

of cases, but mortality rates are high, ranging from 20% to 40%.280,281 The poor prognosis associated

with spontaneous bacterial peritonitis warrants consideration of liver transplantation.

Prophylactic oral or intravenous antibiotics are indicated for three distinct groups of patients with

cirrhosis with ascites: (a) those with gastrointestinal hemorrhage, (b) those with low protein counts in

the ascitic fluid (<10 to 15 g/L), and (c) those who have survived an episode of SBP.282,283 The

preferred antibiotics used in patients with hemorrhage are 7 days of either intravenous ceftriaxone or

oral norfloxacin.283 These antibiotics reduce the incidence of spontaneous bacterial peritonitis from

approximately 15% to 20% to 3% to 9% and cause few side effects.284–286 A meta-analysis evaluating

the use of prophylactic antibiotics in patients with gastrointestinal hemorrhage confirmed the utility of

prophylaxis, with an approximately 30% decrease in the incidence of infection, a 20% decrease in the

incidence of spontaneous bacterial peritonitis and bacteremia, and a 10% improvement in overall

survival.287 In patients with low protein levels in the ascitic fluid, multiple regimens have proved

effective in reducing the incidence of spontaneous bacterial peritonitis, from approximately 20% to less

than 5%.287–289

Hernias and Ascites

Hernias of the anterior abdominal wall occur in up to 20% of patients with cirrhosis. The causes include

increased intra-abdominal pressure and nutritional deficits, with muscular wasting and thinning of the

fascia. If the hernias are left untreated, complications include incarceration, rupture, strangulation, and

leakage. Patients with hernias and decompensated cirrhosis need to be evaluated for liver

transplantation. In patients with stable liver function, hernias should be treated electively, with

preoperative paracentesis to decrease intra-abdominal pressure. No increase in complication rates was

noted in a study comparing the outcome of umbilical hernia repair in patients with and without ascites.

A longer hospital stay and a significantly higher recurrence rate (73% vs. 14%) were noted, however, in

the group of patients with ascites.290–292 We favor the use of abdominal drains to remove the ascites

until the incision is healed, thereby preventing ascites from leaking through the wound. Meticulous fluid

management is essential during the postoperative period to prevent early reaccumulation of ascites.

In patients with severe ascites, TIPS should be performed before hernia repair to ensure a good result.

Emergency repair of hernias complicated by skin breakdown with ascites leak or incarceration or

strangulation is managed in a similar fashion with preoperative large-volume paracentesis, and

aggressive control of ascites postoperatively.

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