Laparoscopic Liver Resection for Hepatocellular Carcinoma

*Melina Vlami, Nikolaos Arkadopoulos and Ioannis Hatzaras*

### **Abstract**

Hepatocellular carcinoma (HCC), remains one of the most common causes of cancer-related death globally. HCC typically arises in the setting of chronic liver disease and cirrhosis and as such, treatment must be balanced between the biology of the tumor, underlying liver function and performance status of the patient. Hepatic resection is the procedure of choice in patients with high-performance status who harbor a solitary mass (regardless of size). Before the first laparoscopic hepatectomy (LH) was described as early as 1991, open hepatectomy (OH) was the only choice for surgical treatment of liver tumors. LH indications were initially based solely on tumor location, size, and type and was only used for partial resection of the anterolateral segments. Since then, LH has been shown to share the benefits of other laparoscopic procedures, such as earlier recovery and discharge, and reduced postoperative pain; these are obtained with no differences in oncologic outcomes compared to open resection. Specific to liver resection, LH can limit the volume of intraoperative blood loss, shorten portal clamp time and decrease overall and liver-specific complications. This chapter will offer an overview of standard steps are in pursuing laparoscopic liver resection, be it for a minor segmentectomy or a lobectomy.

**Keywords:** hepatocellular carcinoma, resection, laparoscopic, technique

#### **1. Introduction**

Despite advances in medical, surgical and locoregional therapies, hepatocellular carcinoma (HCC), the most common primary liver cancer, remains one of the most common causes of cancer-related death globally. Hepatocellular carcinoma is the fifth most common frequently occurring cancer in men, the ninth in women and is the second leading cause of death from cancer worldwide. It is estimated that by 2025 more than 1 million individuals will be affected by liver cancer annually.

HCC typically arises in the setting of chronic liver disease and cirrhosis. In fact, the rate of disease occurrence depends upon the complex interplay between the host, disease and environmental factors. This type of liver cancer contributes to up to 40% of all patient deaths in cirrhosis, making it the single most common cause of death in this patient population. The most prominent and well researched risk factors for HCC are Hepatitis B and C infections, accounting for 50% of all cases. Furthermore, there is a clear geographical distribution in the epidemiology of hepatocellular carcinoma, with the highest incidence seen in developing countries with high rates of chronic hepatitis B and aflatoxin exposure. In contrast the lowest incidence rates are seen in some European countries that also have a lower incidence of the before mentioned risk factors. Interestingly, increasing Hepatitis B vaccination, effective Hepatitis C treatment, reducing levels of aflatoxin exposure are now shifting the global epidemiology of HCC. Metabolic disorders, including Non-Alcoholic Steatohepatitis (NASH) and diabetes mellitus, along with obesity and insulin resistance, are now emerging as direct causative factors of HCC, particularly in the West. These evolving patterns of demographic and epidemiologic characteristics bear interesting implications in the diagnosis and management of patients with HCC [1–4].

#### **2. Management**

Cirrhosis patients should be followed within surveillance programs, that aim for early detection of suspicious nodules and effective treatment. Diagnosis of HCC is achieved with imaging and corroborated with an increased tumor marker alpha-fetoprotein blood (AFP) testing. Percutaneous biopsy is seldomly required for diagnosis.

HCC treatment in the setting of liver cirrhosis must be balanced between the biology of the tumor, and host characteristics such as the underlying liver function, presence or not of portal hypertension and ECOG status of the patient. When evaluating a patient for resection, the functional liver remnant must be carefully assessed and its adequate vascular inflow and outflow ascertained, along with biliary drainage. In the event of marginal functional liver remnant, portal vein embolization should be entertained to decrease the possibility of post-operative liver failure.

The most common staging systems for HCC include the Barcelona Clinic Liver Cancer (BCLC), Cancer of the Liver Italian Program (CLIP), and pathologic tumornode-metastasis (pTNM). In clinical practice, there is no ideal system that can be applicable to every patient in predicting survival [5].

#### **3. The BCLC system**

The Barcelona Clinic Liver Cancer (BCLC) staging system is widely used since its inception and remains the most validated and reliable system for prognostication, due to its treatment recommendations based on stage and its ability to offer predictions on patient survival. The BCLC staging system uses variables addressing tumor stage, liver functional status, physical status and cancer-related symptoms. Subsequently, the BCLC staging system can link the stages described with a treatment algorithm.

The initial authors of the BCLC staging system created a position of safety algorithm that proposes:


The combination of tumor specific staging criteria along with host specific information regarding severity of cirrhosis and symptoms have gained the BCLC *Laparoscopic Liver Resection for Hepatocellular Carcinoma DOI: http://dx.doi.org/10.5772/intechopen.102981*

staging system wide adoption by clinicians around the world. Criticisms of the BCLC staging system focus on the outdated studies the guidelines were based on and the available surgical and intensive care techniques that were available at the time these were first reported.

In fact, using modern approaches to hepatectomy and enhanced postoperative care, several authors were able to demonstrate improved perioperative outcomes and long-term survival for well selected BCLC B and in some cases BCLC C patients managed operatively. These successes point to a trend in pushing the limits of the original more conservative guidelines, thereby offering a better survival to those patients deemed to be good candidates for resection. This endeavor however has to be taken cautiously, and patients that offered resection outside class A should be managed at high volume centers and at minimum be discussed at a multispecialty tumor board. With more and more BCLC staging system patients being considered for hepatectomy, the BCLC system should be revised to reflect modern liver surgery safety standards, and BCLC stages B should not be considered as absolute contraindications to surgery [6–10].

#### **3.1 Tumor-node-metastasis staging system**

According to this system, the most important prognostic factors is the extent or vascular invasion (T1 without, T2 with) within the tumor. Another important prognosticator accounted for in the T portion of the TNM staging system is number of tumors (T3) and direct invasion of other organs (T4). Lymph nodes are only seldomly affected with a histologic diagnosis of HCC, therefore only rarely we observe a N1 status on these patients. Naturally, metastatic disease is denoted as M1 [11].

Although the BCLC staging system has been found to be applicable for all stages of HCC limitations of all of the other systems have been identified. For example, the AJCC (TNM) staging system has limited usefulness since a large portion of HCC patients do not undergo surgery. The most comprehensive comparison between HCC prognostic scores has recently been published by Marrero et al., who analyzed a population homogeneously including all HCC disease strata and drew a retrospective comparison between seven HCC staging systems on a prospectively enrolled cohort: the BCLC system proved to offer the best prognostic score [12].

#### **4. Liver function assessment**

An initial assessment of hepatic function involves liver function testing including measurement of serum levels of bilirubin, aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), measurement of prothrombin time (PT) expressed as international normalized ratio (INR), albumin, and platelet count (surrogate for portal hypertension). Other recommended tests include complete blood count (CBC), blood urea nitrogen (BUN), and creatinine to assess kidney function; creatinine is also an established prognostic marker in patients with liver disease. Further assessment of hepatic functional reserve prior to hepatic resection in patients with cirrhosis may be performed with different tools such as US and MRI elastography (which may provide and quantify the degree of cirrhosis-related fibrosis), and seldomly non-focal liver biopsy, and transjugular liver biopsy with pressure measurements.

The Child-Pugh classification has been traditionally used for the assessment of hepatic functional reserve in patients with cirrhosis. The Child-Pugh score incorporates laboratory measurements (i.e., serum albumin, bilirubin, PT) as well as more subjective clinical assessments of encephalopathy and ascites. It provides a general

estimate of the liver function by classifying patients as having compensated (class A) or decompensated (classes B and C) cirrhosis. Advantages of the Child-Pugh score include ease of performance and the inclusion of non-laboratory, clinical parameters.

An important additional assessment of liver function not included in the Child-Pugh score is an evaluation of signs of clinically significant portal hypertension (i.e., esophagogastric varices, splenomegaly, splenorenal shunts and recanalization of the umbilical vein, thrombocytopenia). Evidence of portal hypertension may be evident on axial imaginsg (CT/MRI). Esophageal varices may be evaluated using esophagogastroduodenoscopy (EGD) or contrastenhanced cross – sectional imaging.

The Model for End-Stage Liver Disease (MELD) is another system for the evaluation of hepatic reserve. MELD is a mathematical model based on regression analysis which employees a numerical scale ranging from 6 (best) to 40 (worst) for individuals 12 years or older. It is derived using three laboratory values (serum bilirubin, creatinine, and INR) and was originally devised to provide an assessment of mortality for patients undergoing transjugular intrahepatic portosystemic shunts (TIPS), but has been therefore incorporated as an algorithm of gauging suitability for liver transplants [13].

Which HCC patient is a candidate for resection?

Patients being considered for resection must have a high-performance status and be medically fit for what is a major operation. In general hepatic resection is the procedure of choice as a potentially curative option in patients with good liver function (generally Child-Pugh Class A without – or with mild – portal hypertension), who harbor a solitary mass (regardless of size) albeit, without major vascular invasion. In addition, the future liver remnant should be measured at minimum 20% in patients without cirrhosis and at least 40% with Child-Pugh Class A cirrhosis. Lastly, the future liver remnant should be projected to have adequate vascular and biliary inflow/outflow. Hepatic resection is controversial in patients with limited but multifocal disease and in those where tumors are seen to invade major vessels [13].

#### **5. Partial hepatectomy**

Surgical removal of a portion of a patient's liver (partial hepatectomy) is beneficial in removing the tumor that it harbors and thereby limiting its growth and spread to other organs. Partial hepatectomy for well-selected patients with HCC can nowadays be performed with low operative morbidity (<25%) and mortality (≤2–5%). Results of large retrospective studies have shown 5-year survival rates for patients with preserved liver function and early-stage HCC of approximately 70%.

Since liver resection for patients with HCC includes removal of functional liver parenchyma in the setting of underlying liver disease, careful patient selection, based on patient characteristics as well as characteristics of the liver and the tumor(s), is essential. Beyond functional liver remnant volume and adequacy of vascular inflow & outflow, technical considerations related to tumor and liver anatomy, must be taken into account before a patient is determined to have potentially resectable disease.

Resection is recommended only in the setting of preserved liver function. The Child-Pugh score provides an estimate of liver function, although it has been suggested that it is more useful as a tool to rule out patients for liver resection (i.e., serving as a means to identify patients with substantially decompensated liver disease). An evaluation of the presence of significant portal hypertension is also an important part of the surgical assessment.
