INTERVENTIONAL ONCOLOGY Hepatic Resection in the Era of Liver- Directed Therapies What every interventional radiologist and surgeon needs to know. BY JOHN J. PARK, MD, PHD, AND JONATHAN KESSLER, MD ver the last decade, there have been dramatic TRANSARTERIAL THERAPY BEFORE LIVER increases in the use of transarterial embo- RESECTION lotherapies for the treatment of hepatic Surgical resection and ablation are considered the malignancies. Although palliative treatments treatments of choice for most resectable liver cancers. Oremain the main driving force behind this trend, part Although the role of neoadjuvant transarterial chemo- of the increased utilization is the result of expanding embolization (TACE) in the setting of resectable tumors indications. Increasingly, transarterial therapies are being has been explored with an abundance of data verifying performed in the neoadjuvant and adjuvant settings, to its safety and efficacy, this role remains controversial downstage tumors, bridge patients to liver transplant, and not widely adopted,1 as no clear survival benefit has and improve postoperative survival. Over this same been proven in this setting. For the majority of patients, period of time, advances in pre- and postoperative man- surgery is not initially an option for a variety of reasons, agement, as well as surgical techniques, have expanded including advanced tumor stage, significant comorbidi- the number of patients who can benefit from surgical ties, inadequate future liver remnant (FLR), or poor resection. As the concomitant use of liver-directed performance status. Furthermore, certain patients are therapies and surgical resection continue to evolve, it deemed unresectable due to the size or location of their is imperative that both the interventional radiologist hepatic tumors. and surgeon understand the implications of patients This subset of patients may potentially be resectable sequentially undergoing each treatment modality. This or eligible for transplantation if their tumors can be article briefly explores the sequential use of transarterial adequately downsized.2,3 As early as 1993, Yu et al dem- therapies before and after major liver resection. onstrated the benefits and safety of performing surgery A B C D Figure 1. Hepatic resection following tumor downstaging with TACE. Contrast-enhanced CT demonstrating one (of two) large, left liver lobe hepatomas (A). Angiogram obtained during the first TACE procedure out of five total procedures (B), with final follow-up Eovist MRI (Bayer HealthCare; 20-minute delay) demonstrating a marked decrease in tumor sizes (C). Portal venous CT following curative extended left hepatectomy with right liver remnant (D). 54 ENDOVASCULAR TODAY SEPTEMBER 2016 VOL. 15, NO. 9 INTERVENTIONAL ONCOLOGY A B A B C D E C D Figure 2. Pre– and post–Y-90 selective internal radiation ther- Figure 3. MRI and ultrasound point shear wave elastography apy (SIRT) with apparent hepatic fibrosis and splenomegaly. (PSWE) after Y-90 SIRT. Eovist MRI before and after Y-90 SIRT Eovist MRI during the hepatobiliary phase before Y-90 SIRT (A) demonstrating prominent fibrotic changes following right and at 4-month follow-up after Y-90 SIRT (B) demonstrating liver lobar radioembolization (A, B). Ultrasound-based PSWE new areas of band-like signal abnormality. Serial prepro- within the areas of apparent fibrosis on MRI before and after cedure (C) and 1- and 4-month (D, E, respectively) postpro- Y-90 SIRT (C, D). No significant changes were apparent in cedure images of the spleen showing progressive splenic fibrosis indices before and after the procedure, despite the enlargement after Y-90 SIRT. robust appearance of bridging fibrosis on MRI (PSWE mean cutoff values, 2–4.5 kPa for METAVIR F0 [normal]; 4.5–5.7 for following downstaging with chemoembolization.4 In F0–F1 [normal to mild]; 5.7–12 for F2–F3 [mild-moderate]; this study, they described the development of adhesions 12–21+ for F3–F4 [moderate-severe]). along the diaphragm and thickening of the gallbladder wall and hepatoduodenal ligaments after chemoem- surgical resection after TARE has been slow to gain bolization. However, these findings did not result in mainstream acceptance. One reason for this reluctance is additional complications during subsequent surgeries. the concern for radiation exposure by the surgical team Moreover, with decreased tumor sizes and increased after radioembolization. With a relatively short half- necrosis, many previously unresectable patients who life (t1/2, = 64.1 h) and limited range of the β particles subsequently underwent chemoembolization became (11 mm; mean distance of 2.5 mm), direct exposure resectable and were able to proceed to hepatic resection. to most of the potent effects of the yttrium-90 (Y-90) Chemoembolization is now considered a safe and β radiation can be mitigated by both time and distance viable option to control or downstage liver cancers prior in patients requiring surgery within the immediate post- to surgical resection and/or “bridge” to transplanta- implantation time frame. Other than the risk of direct tion, prominently being incorporated in many staging radiation exposure to the surgical team, a more practical and treatment guidelines, including the Barcelona Clinic concern is the potential direct and secondary postradia- Liver Cancer and Hong Kong Liver Cancer staging sys- tion effects of the radioembolization treatment on the tems for hepatocellular carcinoma (HCC) and National liver itself, which could include histologic liver fibrosis, Comprehensive Cancer Network guidelines for liver- portal hypertension with splenomegaly, and hepatic vol- dominant metastatic diseases.5-7 Figure 1 shows a patient ume changes (Figure 2).8 with initially unresectable HCC that was successfully Although liver biopsy remains the “gold standard” downstaged with TACE and subsequently treated with for evaluating liver fibrosis, it is invasive and limited by curative major surgical resection. sampling errors. Recently, other noninvasive tools, such Similar to chemoembolization, transarterial radioem- as real-time shear wave elastography, have been shown bolization (TARE) has successfully been used to treat to accurately assess liver fibrosis by measuring liver “stiff- both primary and secondary liver cancers. However, ness.”9 In order to evaluate radioembolization-induced VOL. 15, NO. 9 SEPTEMBER 2016 ENDOVASCULAR TODAY 55 INTERVENTIONAL ONCOLOGY A B C D Figure 4. Right liver HCC successfully downstaged with Y-90 SIRT and treated with curative microwave ablation. Arterial phase CT with a large, hypervascular right liver HCC (A). An angiogram was obtained during selective right segmental radioemboliza- tion (radiation segmentectomy) (B) with follow-up after Y-90 contrasted-enhanced CT demonstrating an interval decrease in tumor size and increase in necrosis (C). A 1-year follow-up CT was performed after radioembolization and curative microwave ablation of the tumor, showing no evidence of recurrent disease (D). liver fibrosis, a recent study utilizing ultrasound shear Figures 4 and 5 illustrate cases in which patients were wave elastography demonstrated that liver segments initially treated with Y-90 radioembolization of their undergoing radioembolization were slightly stiffer or liver tumors followed by successful percutaneous abla- fibrotic at 3 months after Y-90 treatment (mean shear tion (Figure 4) or surgical resection (Figure 5). To further wave elastography, 17.4 kPa) compared with baseline evaluate the implications of radioembolization prior (mean shear wave elastography, 7 kPa). These and other to surgery, Pardo et al recently presented their findings findings have led some in the surgical field to caution from the multicenter, retrospective Post-SIR-Spheres hepatic resection following radioembolization with Surgery study (also known as P4S), which evaluated emphasis on the need for careful patient selection in this the outcomes of liver resection or transplantation population.10,11 after radioembolization.14 A total of 100 patients were Our group is currently evaluating the long-term effects evaluated, with 71 patients undergoing liver resection of Y-90 radioembolization on inducing liver fibrosis using and 29 patients undergoing transplantation after Y-90 sequential ultrasound-based elastography in order to SIRT. Overall, despite many patients having previously track potential radiation-induced liver changes. However, undergone liver-directed therapies (70.5% in the resec- despite the appearance of fibrosis on MRI after Y-90 use, tion arm and 68.9% in the transplant arm) or previous in our experience, this finding does not appear to cor- systemic therapies (50% in the resection arm and 3.4% relate with significant increases in liver stiffness by point in the transplant arm), major complications were similar shear wave elastography (Figure 3). Nevertheless, despite to previously published reports with the exception of these concerns of developing hepatic fibrosis and sub- patients undergoing extended liver resections. The group sequent portal hypertension, many other studies have undergoing extended liver rejections (trisegmentecto- demonstrated that patients can safely undergo liver abla- mies either by conventional means or by ALPPS [asso- tion, surgery, and transplantation after radioemboliza- ciating liver partition and portal vein ligation for staged tion without significant increases in complications.12,13 hepatectomy] procedure) had the highest rate of post- A B C D Courtesy of Dr. Paola Devis,