Hepatocellular Carcinoma: Targeted Therapy and Multidisciplinary P16

Chapter 10 Ultrasound-Guided Liver Resection for Hepatocellular Carcinoma Guido Torzilli Keywords Hepatic surgery · Ultrasound-guided percutaneous therapies · Liver resection · Contrast-enhanced Ultrasonography performed intraoperatively Introduction Hepatic surgery performed without a parenchyma-sparing policy carries relevant risks for patients’ survival due to the not negligible occurrence of postoperative liver failure. In particular, the coexistence of liver cirrhosis in most cases of hepatocellu-lar carcinoma (HCC) has a considerable adverse effect on the surgical results. As a matter of fact, recent series are still associated with mortality rates above 5%, which is not negligible [1]. For this reason and for the broadening of ultrasound-guided percutaneous therapies [2], the role of surgical treatment of HCC as the first-choice treatment is now reserved only for patients with normal bilirubin level, no signs of portal hypertension, and moreover carriers of single small HCC [3]. Imaging tech-niques also have been introduced as aids for surgeons in performing liver resection. In fact, since the early 1980s, intraoperative ultrasonography (IOUS) has been used to guide hepatic surgery in patients with liver cirrhosis [4]. Now, liver resections can be carried out with no mortality, even if cirrhosis is associated, combining the needs for oncological radicality and liver parenchyma sparing. This goal is mainly achievable because of IOUS [5, 6]. Recently, the demonstration of the feasibility and efficacy of contrast-enhanced ultrasonography performed intraoperatively (CE-IOUS) has further stressed the relevance of IOUS guidance during liver surgery [7, 8]. In this chapter, technical aspects of IOUS and the impact of this tool during surgery for HCC for both staging and resection guidance are discussed. G. Torzilli ( ) Department of Surgery, Istituto Clinico Humanitas IRCCS, University of Milan, School of Medicine, Milan, Italy K.M. McMasters, J.-N. Vauthey (eds.), Hepatocellular Carcinoma, 135 DOI 10.1007/978-1-60327-522-4_10, C Springer Science+Business Media, LLC 2011 136 G. Torzilli Technical Aspects For a proper IOUS, high-frequency echoprobes (7.5–10 MHz) are necessary and should have a flat shape to allow their management in deep and narrow spaces. For this purpose, T-shaped probes, interdigital probes, and microconvex probes are available. Main factors for probe selection are its volume, its stability, and the wide-ness of the ultrasonographic scanning window: the best probe should be small, thin in width, and short in transverse length, stable, and with a wide ultrasonographic scanning window. In this sense the microconvex probe represents the best compro-mise among all these requirements. Indeed, the T-shaped probe is more stable but has a lower ratio between lateral length and ultrasonographic scanning window than the microconvex one. Linear transducers with enlarged scanning windows are also available now: in the future this solution may combine stability with larger scanning windows (Fig. 10.1). For CEIOUS, we use a convex 3–6 MHz frequency and 1.88–3.76 MHz har-monic frequency transducer from Aloka (Aloka Co., Tokyo, Japan). Once CEIOUS is needed, 4.8 mL sulphur-hexafluoride microbubbles (SonoVue R , Bracco Imaging, Italy) is injected intravenously through a peripheral vein by the anesthesiologist. For HCC, CEIOUS is used for characterizing the new lesions eventually detected Fig. 10.1 The scanning area of this IOUS image is trapezoidal with a flat upper part that rep-resents the contact area between the probe and the liver and a scanning window which enlarges as it gets deeper. It is also evident, how at IOUS, the portal vein (PV) and the hepatic vein (HV) have different thicknesses of their walls: in particular the wall of the portal branch is thicker, as commonly happens 10 Ultrasound-Guided Liver Resection for Hepatocellular Carcinoma 137 at IOUS [7]: the rationale is to check the vascular pattern during contrast enhance-ment of each new lesion. Because in the case of HCC it is very important to identify the arterial vascularization, which lasts from 20–30 sec, each nodule has to be care-fully evaluated and this demands multiple injections in the presence of multiple nodules. This may no longer be a necessity once the new hepato-specific contrast agents become commercially available for clinical use (for the moment available only in Japan): indeed, behaving as the hepato-specific contrast medium used in magnetic resonance does, they could provide new criteria for nodule differentiation. Furthermore, the contrast enhancement remains visible from several minutes to even hours after injection, thus CEIOUS should gain that panoramicity and reduce the need for reinjections. These features make their use extremely promising and begin further scenarios for the application of CEIOUS in patients who undergo surgery for HCC. Ultrasound Liver Anatomy A background of perfect knowledge of the liver anatomy surgically and ultrasono-graphically is needed in order to perform IOUS properly. For surgical anatomy, Brisbane Terminology is considered here [9]. After entering into the abdominal cav-ity, liver mobilization dividing the round and falciform ligaments, and division of eventual adhesions to free the antero-superior and inferior surfaces of the liver are the steps that should precede the liver exploration with IOUS. Of course, adhesions with other organs or structures should not be divided in the event there is the possi-bility that they are expressions of tumor infiltration: in this eventuality, IOUS could be helpful for ruling out or confirming the tumor invasion and then changing the surgical strategy accordingly. By pulling the round ligament, the liver surface is widely exposed and following the portal branches and the hepatic veins, the liver can be studied in its entirety. The probe should be managed using enough pressure to ensure good contact with the liver surface but not to compress the intrahepatic vascular structures and in par-ticular the hepatic vein. The three main hepatic veins are readily identified at their junction with the inferior vena cava (IVC) positioning the probe at this level and tilting it upward once the confluence of the hepatic veins into the IVC is recog-nized. Then gently withdrawing the probe, the hepatic vein paths can be traced into the liver. Hepatic veins appear as echofree zones into the liver parenchyma with the vessel wall which appears as a thin hyperechogenic line (Fig. 10.1): hepatic vein wall thickness can be larger in the cirrhotic liver and its lumen thinner in function of the hard stiffness of the organ. The portal vein branches can be followed first positioning the probe horizontally above the segment 4 inferior to visualize the first-order bifurcation and then first-, second-, and third-order portal branches can be followed with the probe. Because of the existence of the Glisson’s capsule, the portal pedicles, which run together with the arteries and the bile ducts, have thicker vessel walls compared with the hepatic 138 G. Torzilli vein and for this reason they appear at IOUS as echofree zones surrounded by a thicker hyperechogenic layer (Fig. 10.1); furthermore, other parallel thinner vascu-lar structures are visible, namely the arteries and bile ducts of the Glissonian triad. However, in principle, distinction between hepatic veins and portal branches should be based not only on their appearance but mainly on their anatomy: indeed in the cir-rhoticliver,asalreadymentioned,thevesselwallofthehepaticveincouldbethicker and not immediately differentiable from a peripheral portal branch. Following the portal pedicles at the sectional, segmental, and subsegmental levels and positioning it in relation to the hepatic vein it is possible to precisely define the location of the IOUS target in terms of sections and segments. The appearance of bile ducts at IOUS is worthwhile mentioning because of their peculiarity. Indeed, normally they result as thin echofree zones in the Glissonian triad. Once dilated they appear more evidently as echofree zones and with a serpig-inous path pattern. The element that is difficult to recognize in the IOUS study of the bile ducts is their segmental anatomy. Indeed, bifurcation of sectional and seg-mental ducts is closer to the hilum compared with the portal branches and for that it is possible with one scan to visualize more than a segmental bile duct. If this fact is not considered it could be more difficult to address which part of the liver is not well drained. Conversely, if recognized, IOUS could allow the exact definition of the bile duct anatomy both in normal and pathological conditions. Indications The use of IOUS in liver resections can be schematically divided into three princi-pal phases: the liver exploration for the staging of the disease, the planning of the surgical strategy, and the guidance of the surgical maneuvers. Liver Exploration The hard and irregular surface of a cirrhotic liver makes the detection of small nodules by palpation difficult; IOUS allows the detection of new lesions in around 30% of cases [10]. However, most of the nodules detected by IOUS in the cirrhotic liver are not really tumors: in this way, IOUS introduces the risk of overestimat-ing the tumor stage. Indeed, except for those nodules with mosaic ultrasonographic pattern (Fig. 10.2a) that are malignant in 84% of cases, only 24–30% of hypoe-chogenic (dark) nodules (Fig. 10.2b), and 0–18% of those hyperechogenic (bright) (Fig. 10.2c) are neoplasm [10, 11]. To overcome this problem even biopsy seems inadequate. The only nodule that can be easily differentiated intraoperatively from a HCC or liver metastases is the small hemangioma which is often discovered primarily at IOUS; it has a typical ultrasonographic pattern, and moreover when compressed changes its size and appearance. Therefore, the problem of the dif-ferentiation of the lesions depicted at IOUS exploration becomes crucial. Further 10 Ultrasound-Guided Liver Resection for Hepatocellular Carcinoma 139 Fig. 10.2 (a) A mosaic pattern lesion at IOUS (arrows); (b) a hypoechogenic lesion at IOUS (arrows); (c) a hyperechogenic lesion at IOUS (arrows) improvement in differential diagnosis of liver nodules with IOUS may be expected with the introduction and diffusion of the intraoperative use of the last-generation contrast agents. Contrast-Enhanced Intraoperative Ultrasonography More recently the introduction of CE-IOUS has set the rate for modified operative decision making on 30–40% of cases [7, 8]. Tumor vascularity as a criterion for differentiating the regenerative or dysplastic nodules from the HCC correlates well with the histological evidence of a progressive increase in unpaired arteries from dysplastic to neoplastic nodules in a cirrhotic liver [12]. Certainly, the pattern of vascular enhancement is insufficient for differentiating malignant from nonmalig-nant nodules in a cirrhotic liver with 100% specificity. However, CE-US provides differential diagnosis of FLL with a 95% specificity rate [13]; of course, it must be considered that this last rate referred to another type of lesion when compared to the CEIOUS target. Indeed, the intraoperative exploration takes advantage of the higher resolution of the ultrasonography done in direct contact with the liver. Therefore, the need for differentiating nodules detected at IOUS is mostly focused on lesions smaller than 1 cm: for these nodules the vascularity as the criterion for differential diagnosis is less specific. However, some improvements compared with conventional IOUS could be expected. For this reason, in the early 1990s attempts were made to use CE-IOUS with carbon dioxide as the contrast mate-rial for IOUS, however, the need for arterial catheterization made this technique too invasive [14]. In our preliminary experience CE-IOUS provided remarkable findings, either by adding information on nodular vascularity in patients with HCC, or by detect-ing nodules that were not visible at IOUS, in patients with colorectal cancer liver ... - tailieumienphi.vn