Abstract

To date, the improvements in survival of patients with liver metastases and advances in technology allowed the surgical indications to be extended. In complex cases, however, the possibility of performing a curative hepatic resection collides with the need to preserve a sufficient liver volume to avoid a postoperative hepatic failure. Currently postoperative liver failure is the major cause of death for these patients. In the attempt to overcome this limit in the last decades, we tried to introduce new measures and develop new surgical techniques. From the introduction by Makuuchi in the 1980s of the preoperative portal embolization, many surgical techniques have been proposed and perfected. The aim of this chapter is to describe the new surgical techniques for the approach of complex hepatic metastases.

Keywords: hepatic liver metastases, hepatectomy, liver failure, two-stage hepatectomy, ALPPS

#### 1. Introduction

In the recent decades, the improvement of technology associated with a refinement of preoperative imaging allowed to expand surgical indications, leading to treat patients until a few years ago judged unresectable. These improvements have made major liver surgery more feasible and sure with a clean reduction of morbidity and mortality rate. Today after major hepatectomy, mortality ranges from 0.5 and 4%, making surgery a therapeutic option even in case of advanced disease.

Beyond the extension of surgical indications, the pivotal point remains the possibility to perform a curative resection (R0). Unfortunately, situations such as chronic liver diseases or an extensive disease do not let to achieve a radical resection for the inability to maintain a suitable remnant liver after resection for an adequate postoperative function. Nowadays this is the limits to overcome.

At the current state of knowledge, the future liver remnant (FLR) estimated before surgical resection should be more of 25% of the total liver volume in patients without hepatic disease and of around 40% in the patients with history of liver pathologies (viral chronic hepatitis, alcoholic, nonalcoholic steatohepatitis (NASH), chemotherapeutic damage).

An effective and safe surgery can only be achieved with a perfect knowledge of the surgical anatomy. This anatomy corresponds to a functional liver vascular distribution based on the concept of the anatomical division of the liver proposed by Claude Couinaud, Ton That Tung, and Henri Bismuth, which divides the liver into independent portions that can be handled separately without compromising the function of the remnant liver.

inherent to long time to reach the proper hypertrophy or the impossibility to achieve the desired liver hypertrophy in consideration of the unsuitable size of the

How to Treat Bilobar Liver Metastases: New Surgical Challenges

DOI: http://dx.doi.org/10.5772/intechopen.86745

In the attempt to overcome these limits, in 2012 Schnitzbauer [9] proposed a new surgical approach, named subsequently by Santibanes [10] "associating liver partition and portal vein ligation for staged hepatectomy (ALPPS)." The procedure involves the separation of the future remnant liver from diseased liver through "split" in situ of the hepatic parenchyma in combination with ligation of the portal vein during the first phase. Schnitzbauer [9] reported a hypertrophy of the remnant liver achieved in a very short time (average future remnant liver hypertrophy of 74% in about 9 days). The mechanism by which ALPPS leads to such a dramatic increase in hepatic hypertrophy compared to PVE still needs to be fully clarified. Initially it was thought that the stimulus to hypertrophy was related to the cessation of blood flow between the diseased segments and the FLR, but some authors have subsequently reported how step I in ALPPS leads to an increase in levels of interleukin-6 and tumor necrosis factor-α in liver tissue 1 hour after the procedure compared to PVL [11]. Therefore, rapid hypertrophy could be associated with a systemic increase in circulating growth factors as an inflammatory reaction to parenchymal split. Beyond the first promising results, the high complication rate (44%) with a mortality of 12% described by Schnitzbauer led to several questions about the role and indications of the technique in the surgical community. The subsequent expedients to the original technique and the proposal of more restrictive indications based on practice have led to a significant reduction of the postoperative

morbidity and mortality rate. In fact the results of the most recent ALPPS register

Since its introduction until today, under the term ALPPS, many variations and adaptations of the original technique are grouped. The common thread of all these variants is to try to reduce morbidity and mortality while maintaining an adequate

The purpose of the chapter is to analyze which surgical techniques, to date, can

Within this context of extended resection, postoperative liver failure remains a real concern. The term "small for size syndrome" (SFSS) has been first used in liver transplantation to describe the development of acute liver failure, situation in which the donor's liver was too small for the given recipient. Few years later, Dahm [13] proposed a systematic definition of SFSS. Small for size syndrome was defined as the presence of two of the following criteria in the first three postoperative days: serum bilirubin >6 mg/dL, international normalized ratio (INR) > 2, and the pres-

As in liver transplantation, the extension of surgical indications in the presence of bilobar metastases led to the concept of post-hepatectomy liver failure (PHLF). PHLF is a clinical manifestation that occurs when the remnant liver is not sufficient to provide for metabolic demand. To predict early mortality after extensive hepatectomy in 2005, Balzan [14] proposed that the persistence of either PT < 50% or a serum bilirubin >3 mg/dL on 5 postoperative days is to be considered a predictive mortality index and indicates PHLF. The result of the study demonstrated that the

report more encouraging data, with a 90-day mortality of 9% and serious

remnant liver.

complications of 27% [12].

2. Liver failure

175

hypertrophy response from the liver.

ence of encephalopathy grade III/IV.

be performed in the presence of diffuse liver metastases.

Unfortunately, today it is not uncommon to evaluate patients at the first instance inoperable due to the disseminated hepatic spread. The research of new surgical strategies to effectively extend the number of liver resections and the concept of "resectability" were one of the biggest challenges in oncologic surgery over the last 30 years.

To overcome this limit, new surgical techniques have been proposed with the clear intention of promoting liver regeneration by modifying the procedures first performed in a single procedure in more steps. Moreover in the case of large and complex surgical resections, an accurate study of the liver is recommended to evaluate the postoperative functional reserve with a volumetric and functional assessment (clearance of indocyanine green, scintigraphy, CT, MR).

Laboratory tests on animals and clinical data showed that the closure of portal flow toward a hemiliver induces contralateral lobe hypertrophy. Portal flow redistribution can be achieved with surgical ligation (PVL) or percutaneous embolization (portal vein embolization (PVE)). The purpose of PVE is to increase preoperatively the volume of the future remnant liver to allow the surgery and reduce postoperative morbidity, when the only contraindication to surgery is represented by the initial insufficient remnant liver. The first to propose this technique in the 1980s was Makuuchi, and since then huge progress has been made. Makuuchi and his group [1] first used this technique in 14 patients with cholangiocarcinoma to minimize the possibility of postoperative hepatic dysfunction. The results obtained were encouraging without showing major complications and being able to perform surgical resection in 85% of patients in a timing from 4 to 41 days after embolization.

The experience of Makuuchi marked a crossroad for the birth of a new surgical attitude to approach extended right-side hepatectomy, in fact the procedure was shortly adopted by several surgeons [2–4].

Once the new technique was universally accepted, some surgeons proposed during the next decade a technical progress describing a sequential surgical procedure called "two-stage hepatectomy (TSH)" [5]. To achieve the goal of radical resection in patients with colorectal hepatic metastases, the authors outline a previously therapeutic approach [6]. A procedure includes a first surgical step in which the removal of the lesions of the left lobe associated with the closure of the right portal branch is performed. Liver hypertrophy associated with chemotherapy limits the growth and spread of residual lesions and then allows the patients to undergo surgery in the absence of disease progression and in the presence of a residual volume adequate to prevent postoperative hepatic failure. The feasibility of the procedure was 81% with a mortality rate of 15% for the second stage. At the beginning the technique did not provide for all patients portal embolization, and then the routine use of the latter led to a higher rate of hypertrophy and therefore with a greater rate of patient treated with curative intent [7]. Although the first results were encouraging, the drawback of TSH led to the impossibility of achieving sufficient hypertrophy in an acceptable time to avoid a progression of the disease that in some studies did not allow up to 28% of treated patients to undergo second surgical phase [8]. The reasons of technique failure were due to disease progression inherent to long time to reach the proper hypertrophy or the impossibility to achieve the desired liver hypertrophy in consideration of the unsuitable size of the remnant liver.

In the attempt to overcome these limits, in 2012 Schnitzbauer [9] proposed a new surgical approach, named subsequently by Santibanes [10] "associating liver partition and portal vein ligation for staged hepatectomy (ALPPS)." The procedure involves the separation of the future remnant liver from diseased liver through "split" in situ of the hepatic parenchyma in combination with ligation of the portal vein during the first phase. Schnitzbauer [9] reported a hypertrophy of the remnant liver achieved in a very short time (average future remnant liver hypertrophy of 74% in about 9 days). The mechanism by which ALPPS leads to such a dramatic increase in hepatic hypertrophy compared to PVE still needs to be fully clarified. Initially it was thought that the stimulus to hypertrophy was related to the cessation of blood flow between the diseased segments and the FLR, but some authors have subsequently reported how step I in ALPPS leads to an increase in levels of interleukin-6 and tumor necrosis factor-α in liver tissue 1 hour after the procedure compared to PVL [11]. Therefore, rapid hypertrophy could be associated with a systemic increase in circulating growth factors as an inflammatory reaction to parenchymal split.

Beyond the first promising results, the high complication rate (44%) with a mortality of 12% described by Schnitzbauer led to several questions about the role and indications of the technique in the surgical community. The subsequent expedients to the original technique and the proposal of more restrictive indications based on practice have led to a significant reduction of the postoperative morbidity and mortality rate. In fact the results of the most recent ALPPS register report more encouraging data, with a 90-day mortality of 9% and serious complications of 27% [12].

Since its introduction until today, under the term ALPPS, many variations and adaptations of the original technique are grouped. The common thread of all these variants is to try to reduce morbidity and mortality while maintaining an adequate hypertrophy response from the liver.

The purpose of the chapter is to analyze which surgical techniques, to date, can be performed in the presence of diffuse liver metastases.
