CLINICAL STUDY ABSTRACT

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1 CLINICAL STUDY Arterial Versus Portal Venous Embolization for Induction of Hepatic Hypertrophy before Extended Right Hemihepatectomy in Hilar Cholangiocarcinomas: A Prospective Randomized Study Timm Denecke, MD, Daniel Seehofer, MD, Ingo G. Steffen, MD, Christian Grieser, MD, Lars Stelter, MD, Dirk Schnapauff, MD, Jan Holger Rothe, MD, Andreas Weigelt, MD, Maciej Pech, MD, Jan Langrehr, MD, Pietr Podrabsky, MD, Peter Neuhaus, MD, and Enrique Lopez Hänninen, MD ABSTRACT Purpose: To assess the efficacy and safety of portal vein (PV) embolization versus hepatic artery embolization (HAE) for induction of hepatic hypertrophy before extended right hemihepatectomy in patients with hilar cholangiocarcinoma. Materials and Methods: Fifty patients (female, n 15; male, n 35; age range, y) with hilar cholangiocarcinomas who were planned to undergo extended right hemihepatectomy were prospectively included in In addition to biliary decompression of the left liver, patients were randomized to undergo embolization of the right hepatic artery (with transfemoral access and polyvinyl alcohol [PVA] particles plus coils) or right PV branches (with computed tomography [CT] guided transhepatic access and PVA particles). CT was performed before and approximately 3 weeks after embolization for volumetric assessment of the liver. Results: In the HAE group, median growth of the left lateral segments was 40 ml (P.01), with a median reduction of the whole liver of 10 ml (P.41); adverse events were observed in two of 25 patients (8%), who each developed an abscess in the right liver lobe. In the PV embolization group, median growth of the left lateral segments was 110 ml (P.01), with a median growth of the whole liver of 10 ml (P.92); a subcapsular seroma occurred in one of 25 patients (4%). The median growth of the left lateral segments after PV embolization was significantly greater than after HAE (P.004). Conclusions: Compared with HAE, PV embolization was significantly superior regarding induction of hepatic hypertrophy of the left lateral segments. ABBREVIATIONS HAE hepatic artery embolization, FLR future liver remnant, PV portal vein, PVA polyvinyl alcohol, TAE transarterial catheter embolization For hilar cholangiocarcinomas (ie, Klatskin tumors) and other primary and secondary malignancies of the liver, extensive liver resection represents an option to establish radical complete tumor removal and thereby improve recurrence-free survival (1 6). By using extended right hemihepatectomy, a major part of the hepatic volume will be removed, potentially transcending the functional hepatic reserve necessary to avoid postoperative liver failure. To From the Departments of Radiology (T.D., I.G.S., C.G., L.S., D.Schnapauff, J.H.R., A.W., P.P., E.L.H.); and General, Visceral, and Transplantation Surgery (D.Seehofer, J.L., P.N.), Campus Virchow Klinikum, Charité Universitätsmedizin Berlin, Berlin; and University Clinic for Radiology and Nuclear Medicine (M.P.), Otto-von-Guericke-Universität, Magdeburg, Germany. Received September 15, 2009; final revision received April 18, 2011; accepted April 19, Address correspondence to T.D., Klinik für Radiologie, Campus Virchow Klinkum, Charité Universitätsmedizin Berlin, Augustenburger Platz 1, Berlin, Germany; timm.denecke@charite.de None of the authors have identified a conflict of interest. SIR, 2011 J Vasc Interv Radiol 2011; 22: DOI: /j.jvir

2 Volume 22 Number 9 September minimize this risk, portal vein (PV) embolization of the diseased part of the liver before surgery, with concomitant induction of hypertrophy of the future liver remnant (FLR), have been shown to be feasible (7). Various techniques have been employed successfully, including the use of polyvinyl alcohol (PVA) particles as an embolizing agent, alone or in combination with coils (8,9). Adverse events of PV embolization have been reported in as many as 16% of patients (10 14). Hepatic arterial embolization (HAE) has also been reported to induce hypertrophy of the nonembolized liver when used alone and in a sequential approach combined with PV embolization (15 17). In the past, arterial embolization was even considered as the method of choice by some authors (18). Arterial embolization has a low associated risk, as shown in embolization of hepatocellular carcinomas in cirrhotic livers (4.4% adverse event rate in a study with 2,300 procedures in 850 patients) (19 21). However, it is questionable whether the low complication rates of local transarterial tumor embolization can be maintained when the embolization is extended to an entire liver lobe (22). The purpose of this prospectively randomized study was to compare the achievable hepatic hypertrophy (segments 2 and 3) and intra- and postinterventional complication rates of arterial embolization with the results of PV embolization before extended right hemihepatectomy. MATERIALS AND METHODS Study Design In this prospective, single-center trial, patients with hilar cholangiocarcinomas, resectable by means of an extended right hemihepatectomy, were randomly assigned in a 1:1 ratio to the two study arms. The primary endpoint was volume of the FLR (segments 2 and 3) just before surgery compared with the preintervention baseline; the primary hypothesis was that PV embolization is superior to transarterial catheter embolization (TAE) in inducing hypertrophy of the FLR. The secondary endpoint was the rate of complications of embolization until surgery according to Society of Interventional Radiology (SIR) criteria (23); the secondary hypothesis was that arterial embolization would not lead to a significantly higher rate of major complications than PV embolization. The study complied with the Declaration of Helsinki and the principles of good clinical practice. The study protocol was approved by the institutional review board. Patients For enrollment, patients were assessed with all required imaging material and clinical data in an interdisciplinary consensus panel consisting of liver surgeons (P.N., J.L., and D. Seehofer, with 8 30 years of experience in hepatic surgery) and radiologists (E.L.H. and P.P., with 12 and 20 years of experience in abdominal imaging and interventional radiology, respectively). Tumor location and topography was documented with magnetic resonance (MR) imaging (including MR cholangiopancreatography), computed tomography (CT) with estimation of the liver volume, and endoscopic retrograde cholangiopancreatography, including brush cytology. Inclusion requirements were positive cytologic findings and resectability via extended right hemihepatectomy based on imaging findings and clinical data. In cross-sectional imaging, the PV had to be patent and the left branch had to be free of tumor at the resection line. In defining resectability regarding the volume of the FLR, we used a multifactorial determination and therefore no absolute lower limit was defined for this study. However, significant atrophy of the left lateral segments eg, caused by cholestasis had to be ruled out by cross-sectional imaging. In addition, no upper limit of the FLR was defined, as all patients planned to undergo extended right hemihepatectomy for hilar cholangiocarcinomas at our center receive preoperative right lobe embolization. Exclusion criteria were preexisting occlusion of the PV or hepatic arteries (as assessed by CT), neoadjuvant treatment, pregnancy, uncorrectable coagulopathy, infection or serious vital impairment, inability to give informed consent, and relevant comorbidity (eg, cardiac disease, chronic liver disease) that would prevent the completion of the planned study treatment. Therefore, every patient underwent a detailed physical examination and blood tests for the relevant parameters, plus chest radiography and electrocardiography. After written informed consent was obtained, the patients were randomly assigned to the two study arms by a surgeon and a radiologist (J.L. and E.L.H.) by using presealed envelopes containing the allocation orders. From 2003 until the completion of study enrollment in 2006, a total of 121 patients referred to our center were found to be eligible for surgical therapy. Among these, extended right hemihepatectomy was planned in 69 cases. Of these, 50 patients (female, n 15; male, n 35; age range, y) who met the inclusion criteria were randomized to the HAE or the PV embolization groups (n 25 each). CT Volumetry Contrast-enhanced multiphase helical CT (four- to 64-slice scanners) with a slice thickness of up to 3.75 mm for the venous phase (ie, basis for volumetry) was performed 1 day before embolization to assess the anatomic situation and vascular status and to perform pretreatment baseline volumetry of the whole liver and left lateral segments (segments 2 and 3 according to Couinaud classification). The same CT scanner and examination protocol were used for a reassessment scan that was performed after embolization, 1 day before surgery. Volumetry of the entire liver parenchyma was performed by manual segmentation of the liver silhouette (excluding major hilar vessels, large cysts, and the vena cava) with a noncommercial software tool (Medical Image Editor; Deutsches Herzzentrum Berlin, Berlin, Germany) using the principal of the summation of areas (24). A virtual

3 1256 Arterial vs PV Embolization before Extended Right Hemihepatectomy Denecke et al JVIR resection, with the falciform ligament, left PV branch, confluence of left and middle hepatic veins, and inferior vena cava used as landmarks, revealed the volume of segments 2 and 3 as the FLR. The volumes were determined as absolute volumes (in ml) of the entire liver and the FLR before and after embolization, and calculated as relative FLR (ie, FLR in ml divided by total liver volume in ml 100). Changes in volume are given as absolute changes (in ml) and relative changes (as percentages) versus baseline. Embolization Before embolization, all patients underwent endoscopic retrograde cholangiopancreatography and internal biliary drainage of the left bile duct. The right biliary system was not completely visualized and also not decompressed. In patients with previous endoscopic retrograde cholangiopancreatography and internal drainage before referral to our hospital, any right-sided stents were removed and replaced with left-sided stents. If internal drainage of the left biliary system was not possible, decompression was achieved by external drainage. After biliary decompression, embolization was performed during the following days irrespective of the total serum bilirubin level. Despite this predefined study protocol, initial embolization followed by adjustment of biliary decompression was permitted in patients admitted with right biliary stents to meet the time frame. Patients fasted before the intervention. Antibiotics (ciprofloxacin 400 mg intravenously) were given 1 hour before and 6 hours after the embolizations and biliary interventions for prophylaxis; in case of signs of postintervention infection, further treatment with antibiotic agents was initiated. Besides local anesthesia, pain management consisted of piritramide (14 mg infused intravenously) for both embolization methods. Arterial Embolization Arterial embolization was performed via transfemoral digital subtraction angiography with 5-F angiographic sheath. Aortography (5-F Omni Flush catheter; AngioDynamics, Latham, New York) and selective angiography of the celiac trunk and the mesenteric artery were performed to visualize the individual anatomic situation of the arterial supply to the liver; a 3-F microcatheter (MicroFerret; Cook, Bloomington, Indiana) was introduced into the arteries supplying the right liver lobe by using a inch guide wire (eg, Cirrus; Cook). Embolization was performed with PVA particles ( m, maximum of eight bottles; Contour; Boston Scientific, Natick, Massachusetts) injected over the microcatheter into the right hepatic artery until stasis was achieved. A central coil embolization of the right hepatic artery was performed with one to three inch coils (4 5 mm depending on vessel caliber; Tornado; Cook). In cases of anatomic variants, the procedure was adapted to embolize all hepatic arteries that participated in the supply to right lobe segments 5 8. After removal of the sheath, manual compression of the puncture site was performed, with subsequent compression bandaging for 24 hours (Fig 1). PV Embolization PV embolization was performed by using a percutaneous transhepatic access established ipsilaterally via CT fluoroscopy guided direct puncture (21-gauge coaxial needle, 15 cm length) of the right intrahepatic PV or one of its major branches. A inch guide wire was advanced through the needle into the superior mesenteric vein or the splenic vein (controlled by CT fluoroscopy). The needle was replaced by an introducer system (AccuStick II; Boston Scientific) to switch to a stronger guide wire (0.035-inch Safe-T-J-curve; Cook) according to Seldinger technique. The introducer system was replaced by a 4-F angiography sheath (23-cm length, opaque tip; Brite-tip sheath; Cordis, Bridgewater, New Jersey) over the guide wire to definitively establish access to the PV for the further angiographic intervention. The patient was transferred to the angiography suite, and direct portography was performed to visualize the PV anatomy (Fig 2). A reverse catheter (Sidewinder 1; Cordis) was used to achieve anterograde access to the right portal venous system, a microcatheter was subsequently introduced into the branches of the right PV, and embolization was performed with increasing sizes of PVA particles (approximately four or five bottles of m particles, four bottles of m particles, and three bottles of m particles [Contour, Boston Scientific]; dose shared for separate selective embolization of posterolateral and anteromedial branches of the right PV) until stasis was achieved. This was followed by portography to document the final result of the intervention (Fig 2). During retraction of the sheath, the puncture channel was sealed with 2 ml of fibrinogen (Tissucol Duo; Baxter, Deerfield, Illinois) to avoid bleeding or bile leakage. Follow-up According to the protocol, patients were hospitalized at least for 2 d postoperatively and readmission was planned for definitive surgery 5 weeks later. Within this interval, patients underwent at least weekly clinical and laboratory follow-up, including physical examination, bilirubin measurement, liver function tests, C-reactive protein measurement, and blood counts. In case of clinical symptoms (eg, pain, fever) or increasing infection parameters, further diagnostic measures were initiated if appropriate (eg, ultrasound, CT) and calculated antibiotic therapy was started; associated data are reported only when indicating complications. Statistics SPSS (version 13.0; SPSS, Chicago, Illinois) and R (version 2.8.1; R Foundation for Statistical Computing, Vienna, Austria) software were used for statistical analysis. Calculation of sample size was based on the detection of a 100-mL difference in medians of absolute FLR between the

4 Volume 22 Number 9 September Figure 1. TAE of the right liver lobe with PVA particles. (a) Pretherapeutic celiacography and (b) hepatography after particle embolization and final central coil embolization (arrows). Follow-up CT (c) in axial maximum intensity projection shows enduring complete embolization of the arterial vessels of the right liver lobe (arrows). The stent position was changed from right (b, arrowhead) to left (c, arrowhead) internal biliary drainage after the embolization. Figure 2. Percutaneous transhepatic PV embolization. (a) Direct puncture (arrow, needle) of the right PV under CT fluoroscopy guidance. (b) Subsequent portography after insertion of an angiography sheath with opaque tip (arrow) into the main PV over a guide wire (block arrow) reaching into the superior mesenteric vein. (c) Portography after complete PV embolization of the right liver lobe with PVA particles over a reverse catheter (arrow). The stent position (b and c, arrowhead) was changed from right to left internal drainage after the embolization.

5 1258 Arterial vs PV Embolization before Extended Right Hemihepatectomy Denecke et al JVIR HAE and PV embolization groups assuming an SD of 30% of the medians. With a two-sided type I error rate of 5% and 90% power, a sample size of 25 patients per group was estimated for the primary endpoint. According to histograms, stem-and-leaf plots, and Kolmogorov Smirnov tests, normal distribution of data could not be assumed, so descriptive parameters are given as medians and interquartile ranges (ie, 25th and 75th percentile values), and box plots are used for graphical presentation. Nonpaired data were tested with the Mann Whitney U test, and the Wilcoxon test was applied for paired data. Cross-tables and 2 tests were used for analysis of categoric data. All tests were two-sided with a 5% significance level. RESULTS Patients External biliary drainage of the left lateral segments was necessary in one patient in each group. In 11 cases, the embolization was performed before adjustment of biliary decompression with removal of the right stent and drainage of the left system (HAE group, n 5; PV embolization group, n 6). All patients completed the study treatment with the prescribed embolization and subsequent surgical resection. There were no significant differences in age, sex, or tumor localization between the two groups. Individual clinical course necessitated the advance or delay of surgery for some patients in both groups, which influenced the time interval between embolization and follow-up CT; there was no significant difference between the two groups regarding this parameter (Table 1). In addition, there were no significant differences between total liver volume, absolute volume of left lateral segments, and relative FLR at baseline (Table 2). Hypertrophy In the HAE group, segments 2 and 3 showed a significant increase in absolute (median, 40 ml; P.01) and relative FLR volume (median, 1.6%; P.04), whereas the total liver volume did not change significantly (Table 3). The PV embolization group showed a similar tendency, with significantly increased volume of the absolute (median, 110 ml; P.01) and relative FLR (median 5.2%; P.01) and nonsignificant changes in total liver volume (Table 3). Comparing the two groups, neither the total liver volume after embolization nor the absolute or relative changes in total liver volume were significantly different. Concerning the FLR, the absolute volume of segments 2 and 3 after embolization (P.012) and the absolute (P.004) and relative increases in volume (median, 34.8% vs 12.8%; P.010) were significantly higher in the PV embolization group. Moreover, the relative FLR showed a significantly greater increase in the PV embolization group compared with the HAE group (P.01; Table 3, Fig 3). Table 1. Patient Data Characteristic HAE (n 25) PVE (n 25) P Value Age (y).26 Median IQR Range Sex.76 Male Female 8 7 Interval from embolization to CT (d).11 Median IQR Range Total bilirubin before embolization (mg/dl).18 Median IQR Range Bismuth classification Type I 0 2 Type II 7 3 Type IIIa 4 5 Type IIIb 6 5 Type IV 8 10 Note. HAE hepatic artery embolization; IQR interquartile range; PVE portal venous embolization. Table 2. Liver Volumes at Baseline Parameter HAE (n 25) PVE (n 25) P Value Total liver (ml).55 Median 1,790 1,800 IQR 1,445 2,010 1,605 2,148 Range 1,240 2,550 1,350 2,760 FLR (ml).47 Median IQR Range Relative FLR (%).79 Median IQR Range Note. HAE hepatic artery embolization; FLR future liver remnant; IQR interquartile range; PVE portal venous embolization. Adverse Events In the HAE group, the overall complication rate was 32% (eight of 25), with 24% (n 6) being grade B minor complications (pain within 24 h after embolization requiring medication, n 3; fever, n 3). Two patients (8%) developed fever and upper abdominal pain caused by abscesses in the embolized right liver lobe diagnosed at days 7 and 12 after embolization; both were treated by percuta-

6 Volume 22 Number 9 September Table 3. Changes in Liver Volume Parameter After Embolization Absolute Change Relative Change P Value* P Value Total liver (ml) (absolute volume), HAE (absolute change) Median 1, IQR 1,480/2, to 270 Range 1,200 2, to 870 PVE.92 Median 1, IQR 1,560 2, to 135 Range 1,250 3, to 930 FLR (ml).012 (absolute volume), HAE (absolute change), Median (relative) IQR to Range to to PVE.01 Median IQR 320 to to to 66.0 Range 250 to to to Relative FLR (%).01 (all parameters) HAE.04 Median IQR Range to 12.2 PVE.01 Median IQR Range Note. HAE hepatic artery embolization; FLR future liver remnant; IQR interquartile range; PVE portal venous embolization. Relative FLR is calculated as (FLR in ml / total liver in ml 100). * Statistical intergroup comparison of baseline and follow-up volumes. Comparison of HAE with PVE in volumes after embolization and changes from baseline. neous drainage and antibiotic therapy, and surgery was performed ahead of schedule. Both events were considered as grade D major complications. In the PV embolization group, one patient had an incidental finding of subcapsular fluid accumulation at the right liver lobe on the follow-up CT; no specific therapy was required, and, upon successful resection, the fluid collection was identified as a seroma with a small amount of bile (grade A minor complication). Grade B minor complications in the form of pain occurred in 4% of cases (one of 25) within 24 hours of embolization, and 16% (n 4) had fever during the presurgical interval indicative of cholangitis. Therefore, the overall rate of complications in the PV embolization group was 20%, and all were minor. DISCUSSION PV embolization is the standard method of hepatic hypertrophy induction and is reliably efficient (25,26). In published studies, the increases in absolute and relative volume of segments 2 and 3 after PV embolization of the right liver lobe were reported to be 134 ml and 41%, respectively (8). PVA particles are widely used for PV embolization, as in the present study, and have been demonstrated to be effective (9). In the present study, complete embolization of the right PV branches was performed with good results. With median increases of 110 ml and 35%, respectively, the absolute volume and relative FLR findings were similar to those in other studies. Some studies suggest potentially greater gains in the volume of segments 2 and 3 after PV embolization when segment 4 branches are also embolized (27,28). This was not performed in the present trial, as it would preclude the option to preserve this segment during surgery. In patients with estimated critical postoperative liver function, we prefer to make the final decision on preserving portions of segment 4 at the time of surgery, following reassessment of the tumor extent and the functional capacity of the FLR. This approach was also applied to HAE, thereby occluding all arteries supplying the right liver lobe. The technique of arterial embolization used in this study is a further development of the methodology described by Vogl

7 1260 Arterial vs PV Embolization before Extended Right Hemihepatectomy Denecke et al JVIR Figure 3. Intergroup comparison. Box plots of (a) absolute FLR after embolization and (b) absolute and (c) relative changes of FLR from baseline to follow-up. (PVE, portal venous embolization.) et al (15), and consists of embolization of the arterial periphery with particles to overcome hepatic supply through collateral formation from the left liver or the liver capsule; in addition, a final coil embolization of the particle-filled arteries was performed to reliably avoid arterial reperfusion (this was considered unnecessary for PV embolization). With this technique, arterial embolization also achieved a significant increase in volume of the left lateral segments (median, 40 ml). Nevertheless, the extent of hypertrophy measured by absolute and relative volumes of the left lateral segments was significantly inferior to that after PV embolization in the present study. The mechanisms leading to hypertrophy after PV embolization are believed to compensate for the functional loss of the liver, and are triggered by several stimuli (ie, cytokines such as hepatocyte growth factor, interleukin-6, insulin, and prostaglandin) released according to hepatocellular damage (29). In addition, hemodynamic changes also play an important role. Although the biologic mechanisms of hypertrophy after transarterial embolization have not yet been specifically investigated, it can be assumed that they are mediated by similar pathways, as this procedure mimics PV occlusion on a capillary level and also causes damage to the hepatocytes. The superiority of PV embolization can be explained by its greater effect on the hepatic blood supply and the shift of PV blood flow to the nonembolized liver (29 33). Extensive previous experience with PV embolization indicates a number of associated complications, such as damage to the liver parenchyma, PV injury or thrombosis in the FLR, nontarget embolization, subcapsular hematoma, pseudoaneurysm or hemobilia from arterial injury, arteriovenous fistula, arterioportal shunt, pneumothorax, and sepsis, as well as complications related to surgery (eg, mechanical ileus) and general anesthesia (8,12 14,34,35). Depending on the technique used, these complications have been reported in as many as 16% of patients undergoing PV embolization (12,14). In the present study, few adverse events occurred in the PV embolization group, and none necessitated preoperative intervention or hindered the subsequent resection. It can be speculated whether this was related to the technique, different categorization of adverse events, or the small simple size. Relevant adverse events in the present study were hepatic abscess formations (treated by percutaneous drainage) in two patients (8%) in the HAE group. A study of 6,255 hepatic transarterial oily chemoembolization procedures (22) showed abscess development after 7.5% of procedures (four of 55) in patients with biliary abnormalities prone to ascending biliary infection, in contrast to only 0.2% in other patients. A tendency to develop biliary abscesses after HAE can be explained by the persisting cholestasis with ascending bacteria. In addition, the bile duct wall becomes ischemic after HAE, allowing bacterial invasion. After PV embolization, the arterial supply of the

8 Volume 22 Number 9 September bile ducts is preserved, which could explain why those patients appear less prone to infectious complications. The data presented here suggest that PV embolization should remain the favored modality for hypertrophy induction before extended right hemihepatectomy for hilar cholangiocarcinoma. However, HAE also provokes a relevant gain in FLR. The embolization effects on the tumor itself could be beneficial by slowing tumor growth during the preoperative hypertrophy interval. This could be of value in cases such as in colorectal metastases, in which progression during the preoperative hypertrophy interval can preclude patients from completing the surgical plan (36). The preoperative setting of hepatocellular carcinomas could be another promising indication. Here, arterial embolization may manifest greater hypertrophy rates as a result of the greater dependence of cirrhotic livers on arterial blood supply. However, the higher complication rate observed in the present study has to be kept in mind as a major disadvantage of arterial embolization, potentially altering the clinical course of the patient (eg, surgery ahead of schedule). A further improvement in the effectiveness of HAE could potentially be achieved by choosing alternative embolization materials such as iodized oil mixed with ethanol, which has been shown to enable high hypertrophy rates by a dual embolization of the arteries and PVs by crossing into the portal venous system through intrahepatic arterioportal communications (37,38). However, larger studies of this approach are not yet available. Unilobular right lobe arterial embolization of the liver with radioactive microspheres has also been shown to trigger hypertrophy of the left liver lobe in approximately 20% of cases, in addition to the antitumoral effect (39). However, predisposing factors for this response have not yet been identified, and there are no studies assessing the preoperative setting. A limitation of the present study is the varying preoperative time interval caused by acceleration or delay of the planned resection in view of the clinical situations of some patients. However, the intervals were similarly distributed in the two groups. It can be debated whether a longer preoperative hypertrophy interval would affect the intergroup comparison. However, in PV embolization, most cases of hypertrophy occur within the first month (40), and, balancing potential tumor progression with the desire for timely surgery, the fifth week is an acceptable compromise. We also applied this time interval to the arterial embolization group, even though the optimal hypertrophy interval after arterial embolization is not known. Regarding the second endpoint, the complication rate, our data should be interpreted with caution in view of the limited patient numbers. In summary, in patients with hilar cholangiocarcinoma, before extended right hemihepatectomy, PV embolization is a safe and effective approach that causes significantly superior hepatic hypertrophy induction compared with HAE. REFERENCES 1. Agrawal S, Belghiti J. Oncologic resection for malignant tumors of the liver. Ann Surg 2011; 253: Klatskin G. Adenocarcinoma of the hepatic duct at its bifurcation within the porta hepatic: an unusual tumor with distinctive clinical and pathological features. Am J Med 1965; 38: Dinant S, Gerhards MF, Rauws EA, Busch OR, Gouma DJ, van Gulik TM. Improved outcome of resection of hilar cholangiocarcinoma (Klatskin tumor). Ann Surg Oncol 2006; 13: Neuhaus P, Jonas S, Bechstein WO, et al. Extended resections for hilar cholangiocarcinoma. 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9 1262 Arterial vs PV Embolization before Extended Right Hemihepatectomy Denecke et al JVIR 26. Yokoyama Y, Nagino M, Nishio H, Ebata T, Igami T, Nimura Y. Recent advances in the treatment of hilar cholangiocarcinoma: portal vein embolization. J Hepatobiliary Pancreat Surg 2007; 14: Nagino M, Kamiya J, Kanai M, et al. Right trisegment portal vein embolization for biliary tract carcinoma: technique and clinical utility. Surgery 2000; 127: Kishi Y, Madoff DC, Abdalla EK, et al. Is embolization of segment 4 portal veins before extended right hepatectomy justified? Surgery 2008; 144: Yokoyama Y, Nagino M, Nimura Y. Mechanisms of hepatic regeneration following portal vein embolization and partial hepatectomy: a review. World J Surg 2007; 31: Michalopoulos GK, Zarnegav R. Hepatocyte growth factor. Hepatology 1992; 15: Michalopoulos GK, DeFrances MC. Liver regeneration. Science 1997; 276: Kock NG, Hahnloser P, Roding B, Schenk WG. Interaction between portal venous and hepatic arterial blood flow: an experimental study in the dog. Surgery 1972; 72: Dahmen U, Hall CA, Madrahimov N, Milekhin V, Dirsch O. Regulation of hepatic microcirculation in stepwise liver resection. Acta Gastroenterol Belg 2007; 70: Madoff DC, Hicks ME, Vauthey JN, et al. Transhepatic portal vein embolization: anatomy, indications, and technical considerations. Radiographics 2002; 22: Denys A, Madoff DC, Doenz F, et al. Indications for and limitations of portal vein embolization prior to major hepatic resection for hepatobiliary malignancy. Surg Oncol Clin N Am 2002; 11: de Graaf W, van den Esschert JW, van Lienden KP, van Gulik TM. Induction of tumor growth after preoperative portal vein embolization: is it a real problem? Ann Surg Oncol 2009; 16: Cheng Y, Kan Z, Chen C, et al. Efficacy and safety of preoperative lobar and segmental ablation via transarterial administration of Ethiodol and ethanol mixture for treatment of hepatocellular carcinoma: clinical study. World J Surg 2000; 24: Madoff DC, Gupta S, Pillsbury EP, et al. Transarterial versus transhepatic portal vein embolization to induce selective hepatic hypertrophy: a comparative study in swine. J Vasc Interv Radiol 2007; 18: Gaba RC, Lewandowski RJ, Kulik LM, et al. Radiation lobectomy: preliminary findings of hepatic volumetric response to lobar yttrium-90 radioembolization. Ann Surg Oncol 2009; 16: Ribero D, Abdalla EK, Madoff DC, Donadon M, Loyer EM, Vauthey JN. Portal vein embolization before major hepatectomy and its effects on regeneration, resectability and outcome. Br J Surg 2007; 94: CME TEST QUESTIONS Examinations are available at The CME questions in this issue are derived from the article Arterial Versus Portal Venous Embolization for Induction of Hepatic Hypertrophy before Extended Right Hemihepatectomy in Hilar Cholangiocarcinomas: A Prospective Randomized Study by Denecke et al. 1. Regarding preprocedural patient selection for this study: a) Positive cytology based on endoscopic retrograde cholangiopancreatography brushings was required. b) A baseline minimum future liver remnant (FLR) of 200 ml was needed. c) Patients unresectable on initial computed tomography were included if it was felt the procedure would make them resectable. d) Only those with left-sided biliary stents were included. 2. In comparing the portal venous embolization (PVE) and hepatic artery embolization (HAE) techniques: a) Due to the differing techniques, different embolic materials were used for the two procedures. b) Coils were considered unnecessary for PVE but were used for HAE. c) An identical maximum volume of embolic particles was defined for both procedures. d) Procedures were solely performed under fluoroscopic guidance. 3. Success of the procedures was demonstrated by: a) Increase in the median absolute FLR from a baseline of 280 ml to a median of 420 ml after treatment in the PVE group. b) Increase of the median relative FLR to 34.8% in the HAE group. c) Greater hypertrophy of the FLR after treatment in the PVE group than the HAE group due to embolization of segment 4. d) Significant median total liver volume increase in both groups. 4. When discussing procedure-related complications, the authors note all of the following EXCEPT: a) All complications in the PVE group were considered minor by SIR criteria. b) The complication rate of 20% in the PVE group was comparable to that reported in other studies. c) Hepatic abscesses in the HAE group only required antibiotics and brief postponement of surgery. d) They believe abscesses did not occur in the PVE group as the arterial supply to the bile ducts was preserved.