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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.

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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.

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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