Hepatocellular Carcinoma: Targeted Therapy and Multidisciplinary P14

9 Liver Resection for Hepatocellular Carcinoma 115 Fig. 9.2 Japanese algorithm for resection in cirrhosis (Adapted from [22] used with permission) are safe; ICGR15 30–39%, only wedge resections are safe; ICGR15 ≥40%, only enucleations are safe). This algorithmic approach was prospectively validated in 107 patients; the 30-day mortality rate was zero, and there were no major complications [29]. Evaluation of Future Liver Remnant Volume Computed tomography (CT) can now provide an accurate, reproducible method for preoperatively measuring the volume of the future liver remnant (FLR). The FLR is measured directly by three-dimensional CT volumetry, and the total liver vol-ume is calculated using a mathematical formula that relies on the linear correlation between liver size and body surface area (BSA). The ratio of the CT measure FLR volume/calculated total liver volume (TLV) is defined as the standardized FLR and it provides the percent of TLV remaining after resection [30]. The formula used to estimate TLV based on BSA was recently evaluated in a meta-analysis and recom-mended as one of the least biased and most precise formulas for the estimation of the total liver volume in adults [31] (Fig. 9.3). Although there is a general consensus that the extent of resection that is safe is mainly limited by the function, attention has also focused on the FLR volume after major hepatectomy. In general, a FLR of 20% is considered the minimum safe volume needed following extended hepatic resection in patients with normal underlying liver, while an FLR of 40% is required in patients with chronic liver disease (cirrhosis or hepatitis) [32, 33] (Fig. 9.4). Current suggested indications for PVE in normal, injured, and cirrhotic liver are presented in Fig. 9.5. 116 D. Zorzi et al. Fig. 9.3 Method of systemic preoperative liver volume calculation using three-dimensional CT volumetry. CT outline of the segments included in the measurement of future liver remnant (FLR) volume for a planned extended right hepatectomy (white outline =FLR). (a) The FLR is measured directly by three-dimensional CT volumetry, and the total liver volume (TLV) is calculated using a mathematical formula that relies on the linear correlation between liver size and body surface area (BSA). The ratio of the CT measure FLR volume/calculated total liver volume (TLV) is defined as the standardized FLR (sFLR) and it provides the percent of TLV remaining after resection Preoperative Therapy Transarterial Chemoembolization (TACE) and Portal Vein Embolization (PVE) In patients who are otherwise candidates for hepatic resection, an inadequate FLR volume – ≤20 or <40% of the estimated TLV in patients with normal or cirrhotic liver, respectively – may be the only obstacle to curative resection. Three-dimensionalCTvolumetryandcalculationoftheFLRallowstheplanningofhepatic resection to be individualized for each patient. Portal vein embolization (PVE) can be performed to prime the growth of the anticipated FLR, thereby making a major or extended hepatectomy possible. PVE is safe with less than a 5% complication rate, causes little periportal reaction, and generates durable portal vein occlusion especially when used in com-bination with coils. PVE has been shown to increase both the size of the FLR as well as the percentage of indocyanine green (ICG) excretion and bile volume flow in the remnant liver. In addition, in patients with chronic liver disease PVE has also been reported to decrease the incidence of postoperative complications, intensive care unit stay, and the total hospital stay after major hepatic resection. Thus, the 9 Liver Resection for Hepatocellular Carcinoma 117 Fig. 9.4 Standardized calculation of future liver remnant (FLR) volume accurately predicts the likelihood of postoperative complications after hepatic resection in normal liver (a) and in chronic liver disease (b). (a) Complication rate stratified by standardized future liver remnant (% FLR) volume in relation to FLR in normal liver; 90% of patients with a % FLR of 20% or less had com-plications; 39% of patients with a % FLR of greater than 20% had complications (P = 0.003) [33]. (b) A comparison of FLR volume of patients who died of liver failure and those without liver fail-ure after surgery in chronic liver disease. Remnant liver volume in patients who died of liver failure was significantly smaller than that in patients who did not die of liver failure (P = 0.0008) and it was never more than 250 mL/m2 (From [33], used with permission) Fig. 9.5 Indications for portal vein embolization (PVE). There is a consensus that in patients treated with aggressive preoperative chemotherapy, the remnant liver volume should be at least 30% of the total liver volume to avoid a high risk of complications following hepatic resection. BMI, body mass index (From [34], used with permission) selective use of PVE may enable safe and potentially curative extended hepatec-tomy in a subset of patients with advanced hepatobiliary malignancies who would otherwise have been marginal candidates for resection. Palavecino etal.[35] reportedon54 patientswho underwent major hepatic resec-tion for HCC with or without PVE before resection. This study demonstrates that PVE before major hepatectomy for HCC is associated with decreased perioperative mortality. The overall and disease-free survival rates were similar between patients 118 D. Zorzi et al. Fig. 9.6 Overall survival after major hepatectomy in patients with and without preoperative por-tal vein embolization (PVE), excluding postoperative deaths (P = 0.35) (From [35], used with permission) who underwent major hepatectomy with and without PVE (Fig. 9.6). Thus, PVE increases the safety of major hepatectomy in patients with HCC without compro-mising long-term oncologic outcomes. Because the main blood supply for HCC is the hepatic artery and PVE results in increased hepatic arterial flow, concerns have been raised about the potential for accelerated tumor growth after PVE [36, 37]. To avoid this possibility, TACE has been proposed as a complementary procedure to PVE in patients with HCC (Fig. 9.7). TACE eliminates the arterial blood supply to the tumor and embolizes potential arteriovenous shunts resulting from cirrhosis and/or HCC that attenuate the effects of PVE. In addition, 60–80% complete necrosis of tumor can be achieved by the combination of TACE and PVE [38, 39]. Our results support a study by Ogata et al. [38] in which patients who underwent TACE before PVE had improved disease-free survival and increased FLR hypertrophy than patients who underwent PVE alone [35] (Fig. 9.8). Our current recommendation for those patients with bilo-bar HCC and tumor nodules in the FLR is to perform TACE before PVE to avoid tumor growth in the FLR after PVE. Chemotherapy Sorafenib is an oral multikinase inhibitor, which exerts an antiangiogenic effect by targeting vascular endothelial growth factor receptors (VEGFRs) 9 Liver Resection for Hepatocellular Carcinoma 119 Fig.9.7 Sequentialtransartherialchemoembolization(TACE)andportalveinembolization(PVE) in cirrhotic liver. A 74-year-old male patient HCV genotype 2b with a 12.5 hepatocellular car-cinoma involving the right liver with periportal fibrosis and focal bridging. (a, b) Future liver remnant (FLR) volume of segments 1, 2, 3, and 4 equal to 27%. Computed tomography following TACE and right PVE shows hypertrophy of the FLR (47%) (c). Right hepatectomy was performed. The specimen indicated complete pathologic response with no residual tumor. The patient had no evidence of disease 53 months postresection (d) and platelet-derived growth factor receptor (PDGFR). Recently, a randomized, placebo-controlled phase III trial of sorafenib reported an improvement in median overall survival along with increased time to progression and disease control rate in advanced HCC [40]. There is no evidence that sorafenib has a role as a neoadjuvant agent in downstaging patients to render them resectable because the response rate to sorafenib is only 3%. In contrast the PIAF treatment regimen (platinum, interferon, adriamycin, and 5 FU) allows a selected group of patients with normal liver and HCC confined to the liver to become eligible for aggressive surgical techniques [41, 42] (Fig. 9.9). Using the PIAF regimen in patients with preserved liver function Lau et al. found 18% major tumor response rate (more than 50% reduction in tumor size). Furthermore, 10% percent of the entire cohort, who presented with tumors that were considered unresectable, underwent subsequent complete resection after chemotherapy; 53% of the resected patients were alive 3 years after hepatic resection [43]. ... - tailieumienphi.vn