**3. Laparoscopic liver surgery for malignancy**

After becoming comfortable with resection of benign lesions, the logical progression in the development of a laparoscopic liver program is the resection of malignant lesions. These lesions require an increased degree of skill on the part of the surgeons in order to attain adequate margins and maintain oncologic adequacy. The presence of cirrhosis in the setting of HCC or steatohepatitis following neoadjuvant chemotherapy for colorectal metastasis make proper patient selection and timing of operation critical. The consideration of adjunctive techniques such as transarterial chemoemboliztion for preoperative downstaging also becomes important. Here, we will discuss laparoscopic management of the two most common malignant hepatic tumors: colorectal metastases and hepatocellular carcinoma.

#### **3.1 Colorectal metastases**

Colorectal metastases are the most common malignant hepatic tumor. Results following open resection of these lesions have been excellent, with 5 year survival rates exceeding 50% in many centers (House, MG et al 2010). Such outcomes have set a high standard by which laparoscopic resection must be measured. The adoption of laparoscopy to this field has been hindered by concerns of tumor seeding at port sates and the possibility of missing extrahepatic lesions by inadequate inspection of the peritoneal cavity(Hsu, TC 2008; Johnstone, PA et al 1996). These hurdles have slowly been brought down, and laparoscopic resection is now a standard part of the therapeutic arsenal for hepatic malignancy.

#### **3.1.2 Patient selection**

Patient selection criteria for laparoscopic resection of colorectal metastases are similar to those applied for open resection. Initial evaluation requires precise definition of tumor anatomy and exclusion of extrahepatic disease. We favor triple phase CT as the initial radiographic evaluation. When combined with digital arterial reconstruction, evaluation of aberrant vascular anatomy, which can be present in nearly half of all patients, is afforded. Evaluation of baseline liver function is performed with evaluation of bilirubin, INR, and albumin. A thorough history and physical exam is necessary to assess general fitness for major abdominal surgery. Tumor resectability is defined by the SSAT as an expected negative margin resection with preservation of at least 2 contiguous hepatic segments with adequate inflow, outflow, and biliary drainage and a future liver remnant of more than 20% for normal parenchyma(Charnsangavej, C et al 2006).

#### **3.1.3 Neoadjuvant therapy**

The use of chemotherapy and chemoradiation for metastatic colon and rectal cancer has become a mainstay of therapy. Modern chemotherapeutic regimens generally consist of 5 fluorouracil combined with either oxaliplatin (FOLFOX) or irinotecan (FOLFIRI) have produced excellent response rates, and have been able to render 10-30% of previously unresectable disease amenable to surgical therapy. Agents such as cetuximab and bevacizumab have shown even better response rates. This efficacy is not without a price,

Laparoscopic Liver Resection 71

(Bruix, J & Llovet, JM 2002). One of the major limiting factors in preventing resectability is impaired hepatic function, with the vast majority of cases in Western patients developing in the background of cirrhosis. Thus, appropriate patient selection becomes paramount in achieving successful outcomes. Because of these limitations, the role of laparoscopic liver

Much of the patient selection process for resection of HCC centers around assessment of the underlying liver parenchyma. The Child-Pugh classification system provides a rough framework from which to base the selection process. In generally, Child A patients are able to tolerate limited forms of resection, while Child B and C patients are typically referred for more palliative procedures such as systemic therapy or transarterial chemoembolization. In the West, assessment is directed at determining the presence of significant portal hypertension. Generally, patients with hepatic-venous pressure gradient of less than 10, esophageal varices of no greater than grade 1, and platelet counts of over 100,000 are

A common technique in Eastern centers is the assessment of indocyanine green clearance rate (ICG). This technique involves the injection of an organic dye which is then measured in the peripheral blood after a 15 minute interval. Clearance of the dye is used as a surrogate for hepatic metabolic function. ICG retention of no more than 10-20% is considered to be acceptable. Using this technique in 1056 consecutive patients with normal bilirubin and no ascites, Imamura has been able to achieve hepatic resection with zero operative mortality

Advances in imaging technology have lead to the increasing use of systemic liver volumetry as a preoperative risk assessment tool. A future liver remnant to standard liver volume ratio of greater than 20% is considered safe in patients with healthy liver parenchyma, while ratios of 30-40% are considered necessary for patients with compensated cirrhosis. An insufficient future liver remnant may be addressed with the use of adjunctive techniques such as portal vein embolization, which will be discussed in greater detail in the section on

Tumor related factors that preclude surgical resection include extrahepatic disease and invasion of the main portal vein, vena cava, and common hepatic artery. Multinodular disease that can't be resected with an adequate future liver remnant is also a relative contraindication to resection, although there is a role for resection of the dominant lesion with radiofrequency ablation of the remaining disease in highly selected cases. Although size alone is not a criteria for resectability, there is a practical limit to the size of lesion that can be safely approached laparoscopically. The recent international position statement for laparoscopic liver surgery recommends limitation of the laparoscopic approach to tumors

Unlike the case of hepatic colorectal metastases, there does appear to be a benefit to wider surgical margins in patients with HCC. For patients with solitary HCC lacking vascular invasion, a margin of at least 2cm has proven beneficial in a randomized controlled trial setting. Furthermore, the tendency of HCC to spread via the portal venous system favors the use of planned anatomic resection in patients with adequate hepatic reserve. The inability to perform anatomic resection should not be considered a contraindication, however, as more

<5cm in diameter for all but the most experienced of centers (Buell, JF et al 2009a).

**3.2.2 Technical considerations and oncologic adequacy** 

resection has remained more limited than for other disease states.

considered acceptable risk. In addition, bilirubin levels must be normal.

**3.2.1 Patient selection** 

(Imamura, H et al 2003).

resection in cirrhotics.

however. Bevacizumab has a black box warning for spontaneous intestinal perforation. Traditional chemotherapeutic combinations are hepatotoxic, leading to the phenomenon of chemotherapy associated steatohepatitis (CASH). These considerations are important, as patients are often referred for hepatic surgery after neoadjuvant therapy has been initiated.

#### **3.1.4 Operative considerations and oncologic adequacy**

The most critical factor to producing positive outcomes is the attainment of negative operative margins (R0 resection). Facility with laparoscopic intraoperative ultrasound is a must for surgeons approaching malignant liver lesions, allowing for precise definition of tumor anatomy and planning of resection planes. As long as negative microscopic margins are obtained, there does not appear to be a minimum necessary margin width (Pawlik, TM et al 2005).

The approach to synchronous disease has received considerable attention, as it will be present in up to 25% of patients with colorectal liver metastases (Martin, RC et al 2009). There are three possible surgical strategies in this setting: the classic approach of colorectal resection followed by hepatectomy, a simultaneous resection of colorectal and hepatic disease, and a reverse strategy of metastasectomy followed by primary tumor resection. The drawback of the classic strategy is the delay in metastasectomy while patients receive adjuvant therapy. The combined strategy eliminates this delay, at the cost of greater surgical insult with possibly higher morbidity. The reverse strategy was described to eliminate the delay in metastasectomy while avoiding the surgical insult of the combined approach. With appropriate patient selection, groups from MD Anderson and the University of Louisville have demonstrated that the combined approach can be undertaken without increased morbidity and mortality. Brouquet's analysis of all three strategies found similar morbidity, mortality, and survival across groups, showing that no approach is clearly superior for all patients (Brouquet, A et al 2010).

With increasing worldwide experience of laparoscopic resection of colorectal metastases, the oncologic integrity of laparoscopy compared with open techniques has been shown to be comparable. Nguyen's review of the world literature found only one case of port site recurrence, which occurred in a case of metastatic renal cell carcinoma that ruptured prior to resection (Nguyen, KT et al 2009). Castaing's comparison of 60 patients undergoing laparoscopic resection and 60 patients undergoing open resection provided the first evidence of long term efficacy of laparoscopic resection for colorectal metastases. Five year survival in the laparoscopic group in this series was 62%, which was comparable to the 56% five year survival in the open group. There was no difference in width of resection margins between groups, while the laparoscopic group included a greater percentage of patients undergoing combined hepatic and colorectal resection (Castaing, D et al 2009). Such results confirm that laparoscopic resection is a safe and effective alternative to open surgery for hepatic colorectal metastases.

#### **3.2 Hepatocellular carcinoma**

Hepatocellular carcinoma (HCC) is the sixth most common malignancy and the third most common cause of cancer death worldwide (Parkin, DM et al 2005). In the United States, where chronic hepatitis C infection is the main risk factor, there has been an increase in the incidence of HCC over the past several decades (El-Serag, HB & Mason, AC 1999). Most patients present with relatively advanced disease, making curative treatment such as resection and liver transplantation applicable in only 30-40% of patients in Western centers

however. Bevacizumab has a black box warning for spontaneous intestinal perforation. Traditional chemotherapeutic combinations are hepatotoxic, leading to the phenomenon of chemotherapy associated steatohepatitis (CASH). These considerations are important, as patients are often referred for hepatic surgery after neoadjuvant therapy has been initiated.

The most critical factor to producing positive outcomes is the attainment of negative operative margins (R0 resection). Facility with laparoscopic intraoperative ultrasound is a must for surgeons approaching malignant liver lesions, allowing for precise definition of tumor anatomy and planning of resection planes. As long as negative microscopic margins are obtained, there does not appear to be a minimum necessary margin width (Pawlik, TM

The approach to synchronous disease has received considerable attention, as it will be present in up to 25% of patients with colorectal liver metastases (Martin, RC et al 2009). There are three possible surgical strategies in this setting: the classic approach of colorectal resection followed by hepatectomy, a simultaneous resection of colorectal and hepatic disease, and a reverse strategy of metastasectomy followed by primary tumor resection. The drawback of the classic strategy is the delay in metastasectomy while patients receive adjuvant therapy. The combined strategy eliminates this delay, at the cost of greater surgical insult with possibly higher morbidity. The reverse strategy was described to eliminate the delay in metastasectomy while avoiding the surgical insult of the combined approach. With appropriate patient selection, groups from MD Anderson and the University of Louisville have demonstrated that the combined approach can be undertaken without increased morbidity and mortality. Brouquet's analysis of all three strategies found similar morbidity, mortality, and survival across groups, showing that no approach is clearly superior for all

With increasing worldwide experience of laparoscopic resection of colorectal metastases, the oncologic integrity of laparoscopy compared with open techniques has been shown to be comparable. Nguyen's review of the world literature found only one case of port site recurrence, which occurred in a case of metastatic renal cell carcinoma that ruptured prior to resection (Nguyen, KT et al 2009). Castaing's comparison of 60 patients undergoing laparoscopic resection and 60 patients undergoing open resection provided the first evidence of long term efficacy of laparoscopic resection for colorectal metastases. Five year survival in the laparoscopic group in this series was 62%, which was comparable to the 56% five year survival in the open group. There was no difference in width of resection margins between groups, while the laparoscopic group included a greater percentage of patients undergoing combined hepatic and colorectal resection (Castaing, D et al 2009). Such results confirm that laparoscopic resection is a safe and effective alternative to open surgery for

Hepatocellular carcinoma (HCC) is the sixth most common malignancy and the third most common cause of cancer death worldwide (Parkin, DM et al 2005). In the United States, where chronic hepatitis C infection is the main risk factor, there has been an increase in the incidence of HCC over the past several decades (El-Serag, HB & Mason, AC 1999). Most patients present with relatively advanced disease, making curative treatment such as resection and liver transplantation applicable in only 30-40% of patients in Western centers

**3.1.4 Operative considerations and oncologic adequacy** 

et al 2005).

patients (Brouquet, A et al 2010).

hepatic colorectal metastases.

**3.2 Hepatocellular carcinoma** 

(Bruix, J & Llovet, JM 2002). One of the major limiting factors in preventing resectability is impaired hepatic function, with the vast majority of cases in Western patients developing in the background of cirrhosis. Thus, appropriate patient selection becomes paramount in achieving successful outcomes. Because of these limitations, the role of laparoscopic liver resection has remained more limited than for other disease states.
