Nonembolized Lobe Research Articles

Characterization of Microwave Generator Energy and Ablation Volumes following Transarterial Embolization in an In Vivo Porcine Liver Model

PurposeTo characterize the relationship between ablation zone volume (AZV) and microwave ablation (MWA) energy in an in vivo porcine liver model following arterial embolization. Materials and MethodsWith Institutional Animal Care and Use Committee (IACUC) approval, 11 female swine underwent either right (n = 5) or left (n = 6) hepatic artery embolization under fluoroscopic guidance. Subsequently, ultrasound (US)-guided MWA was performed in each liver segment (left lateral, left medial, right medial, and right lateral) at either 30 W (n = 4 lobes), 60 W (n = 4), 65 W (n = 20), 90 W (n = 8), 120 W (n = 4), or 140 W (n = 4) continuously for 5 minutes. Postprocedural volumetric segmentation was performed on standardized multiphase T1 magnetic resonance (MR) imaging sequences. ResultsMean AZVs in embolized lobes (15.8 mL ± SD 10.6) were significantly larger than those in nonembolized lobes (11.2 mL ± SD 6.5, P < .01). MWA energy demonstrated significant positive linear correlation with both embolized (R2 = 0.66, P < .01) and nonembolized (R2 = 0.64, P < .01) lobes. The slope of the linear models corresponded to a 0.95 mL/kJ (SD ± 0.16) and 0.54 mL/kJ (SD ± 0.09) increase in ablation volume per applied kilojoule of energy (E) in embolized and nonembolized lobes, respectively. In the multivariate model, embolization status significantly modified the relationship between E and AZV as described by the following interaction term: 0.42∗E∗(embolization status) (P = .031). ConclusionsLinear models demonstrated a near 1.8-fold increase in ratio of AZV per unit E, R(AZV:E), when applied to embolized lobes relative to nonembolized lobes. Absolute AZV differences between embolized and nonembolized lobes were greater at higher-power MWA.

Portal vein embolization prior to major hepatectomy: A multidisciplinary approach for advanced liver tumors in Chile

One of the main limitations to achieving a complete tumor resection in patients with technically resectable liver tumors is the presence of a small future liver remnant (FLR). Portal vein embolization (PVE) allows hypertrophy of the non-embolized lobe, reducing the risk of postoperative liver failure. To describe the experience of portal embolization prior to hepatectomy and its effectiveness in converting advanced unresectable liver tumors into resectable tumors. Non-concurrent cohort study. All patients who underwent PVE before hepatectomy between 2016 and 2020 in our center were included. Demographic and diagnostic variables, pre and post-PVE volumes, perioperative variables, and global and disease-free survival were analyzed. Nineteen patients were included. Median age 66 (54-72) years and 57.9% (n= 11) were women. Bilateral metastases were present in 78.9% (n= 15). Sixteen patients (84.2%) received neoadjuvant chemotherapy. One patient (5.3%) had a complication after PVE. The median time between embolization and volumetry was 5.3 weeks (4.7-7.1). Median FLR before and after PVE were 19.8% (16.2-27.7) and 30% (25.2-40.5), respectively. The median percentage of hypertrophy was 48% (40.4-76.5). Fifteen patients (78.9%) underwent hepatectomy. Significant complications occurred in 26.6% (n= 4); among them, three patients (20%) presented postoperative liver failure. PVE is safe and effective in promoting FLR hypertrophy in the presence of chemotherapy, allowing patients with advanced liver tumors to undergo surgery with curative intent.

Liver regeneration after portal vein embolization: comparison between absolute ethanol and N-butyl-cyanoacrylate in an in vivo rat model.

To compare the effects of absolute ethanol (ethanol) and N-butyl-cyanoacrylate (NBCA) on non-embolized liver lobe regeneration in a rat model. Twenty-seven Sprague-Dawley rats underwent portal vein embolization (PVE) using ethanol:lipiodol, 1:1 (ethanol group, n = 11, 40.74%), NBCA:lipiodol, 1:1 (NBCA group, n = 11, 40.74%), or sham treatment (sham group, n = 5, 18.52%). The non-embolized and embolized lobe-to-whole liver weight ratios 14 days after PVE were compared among the groups (n = 5, 18.52%). The expressions of CD68 and Ki-67 and embolized-lobe necrotic area percentages one day after PVE were compared between the ethanol (n = 3, 11.11%) and NBCA (n = 3, 11.11%) groups. The non-embolized lobe-to-whole liver weight ratio after PVE was significantly higher in the NBCA group (n = 5, 33.33%) than in the ethanol group (n = 5, 33.33%) (84.28% ± 1.53% vs. 76.88% ± 4.12%, P = 0.029). The embolized lobe-to-whole liver weight ratio after PVE was significantly lower in the NBCA group than in the ethanol group (15.72% ± 1.53% vs. 23.12% ± 4.12%, P = 0.029). The proportions of CD68- and Ki-67-positive cells in the non-embolized lobe after PVE were significantly higher in the NBCA group (n = 30, 50%) than in the ethanol group (n = 30, 50%) [60 (48-79) vs. 55 (37-70), P = 0.003; 1 (0-2) vs. 1 (0-2), P = 0.004]. The embolized-lobe necrotic area percentage after PVE was significantly larger in the NBCA group (n = 30, 50%) than in the ethanol group (n = 30, 50%) [29.46 (12.56-83.90%) vs. 16.34 (3.22-32.0%), P < 0.001]. PVE with NBCA induced a larger necrotic area in the embolized lobe and promoted greater non-embolized liver lobe regeneration compared with PVE with ethanol.

Increased Hepatic Microvascular Density, Oxygenation, and VEGF in the Hypertrophic Lobe following Portal Vein Embolization in Rabbits

Introduction: The microvascular events following portal vein embolization (PVE) are poorly understood despite the pivotal role of the microcirculation in liver regeneration and tumor progression. We aimed to assess the changes in hepatic microvascular perfusion and neo-angiogenesis after experimental PVE. Methods: PVE of the cranial liver lobes was performed in 12 New Zealand White rabbits divided into 2 groups of permanent (P-PVE) and reversible PVE (R-PVE), respectively. Hepatobiliary scintigraphy and CT were used to evaluate hepatic function and volume. Hepatic microcirculation was assessed using a handheld vital microscope (Cytocam) to measure microvascular density (total vessel density; TVD) before PVE, right after PVE, and 20 min after PVE, as well as at 14 days (D14 post-PVE) and 35 days (D35 post-PVE). Additionally, on D35, microvascular PO₂ and liver parenchymal VEGF were assessed. Results: Eleven rabbits were included after PVE (R-PVE, n = 5; P-PVE, n = 6). TVD in the nonembo­lized (hypertrophic) lobes was higher than in the embolized (atrophic) lobes of the P-PVE group at D35 post-PVE (36.7 ± 7.2 vs. 23.4 ± 4.9 mm/mm²; p < 0.05). In the R-PVE group, TVD in the nonembolized lobes was not increased at D35. Function and volume were increased in the nonembolized lobes of the P-PVE group compared to the embolized lobes, but not in the R-PVE group. Likewise, the mmicrovascular PO₂ and VEGF staining rate were higher in the nonembolized lobes of the P-PVE group at D35 post-PVE. Discussion/Conclusion: Successful volumetric and functional hypertrophy of the nonembolized lobe was accompanied by microvascular alterations featuring increased neo-angiogenesis, microvascular density, and microvascular oxygen pressure following P-PVE.

Vascular Redistribution for SIRT—A Quantitative Assessment of Treatment Success and Long-Term Analysis of Recurrence and Survival Outcomes

Abstract Aim Flow redistribution is not uncommonly performed as a treatment strategy to optimize delivery of radioembolization particles to the liver. We quantitatively evaluated the effect of vessel embolization to promote flow redistribution when performing selective internal radiation therapy (SIRT) for liver metastases, and assessed long-term outcomes of treatment. Materials and Methods One hundred and fifty-eight SIRT procedures over an 8-year period were retrospectively reviewed. Twenty-three patients who underwent partial/whole embolization of the left hepatic artery were compared to a control group of 18 patients who did not receive any hepatic embolization as part of their work up. Counts were measured for each patient on both the post-99mTcMAA injection, and the post-90Y microspheres injection imaging. Recurrence and survival rates were also measured. Results A statistically significant shift in the right:left ratio between planning and treatment procedures was seen in patients who had vessel embolization in favor of the embolized lobe (p = 0.014). There was no significant difference in the time to recurrence in the embolized lobes versus the nonembolized lobes. No significant difference in overall survival was detected between the two cohorts. Conclusion To facilitate safe whole liver treatment, it is sometimes necessary to partially or completely occlude main or accessory hepatic arteries. This study shows that the success of flow redistribution strategies can be quantitatively measured, and there is no adverse impact on time to recurrence or overall survival outcomes.

Quantitative assessment of liver function using hepatobiliary scintigraphy: the effect of microcirculatory alterations after portal vein embolization.

Hepatobiliary scintigraphy using technetium-99m mebrofenin has been validated as a quantitative liver function test. Preoperative portal vein embolization (PVE) is performed in patients to increase future remnant liver function and volume. Changes in hepatic microcirculation after PVE remain largely unknown and may influence the uptake of mebrofenin. The aim was to evaluate microcirculatory changes after PVE to examine differences in perfusion that might influence the uptake of mebrofenin, and consequently, assessment of function. Patients undergoing liver resection with or without preoperative PVE were included. Future remnant liver volume and function were measured before and after PVE. Hepatic microcirculation was measured in the embolized and the nonembolized lobes during resection. Microcirculatory flow index, perfused vessel density, sinusoidal diameter and red blood cell velocity were assessed. A total of 16 patients, eight with preoperative PVE and eight control patients without PVE, were included. After PVE, both function and volume of the nonembolized lobe were significantly increased, and the functional increase exceeded the increase in volume. Perfused vessel density and sinusoidal diameter were significantly higher in the nonembolized liver lobe (P<0.002 and <0.04). No significant differences between both lobes were found concerning microcirculatory flow index or red blood cell velocity. After PVE, the nonembolized lobe had a significantly higher (functional) microvascular density compared with the embolized lobe, without differences in microvascular flow. These findings indicate that the measured functional increase using hepatobiliary scintigraphy, which exceeded the volumetric increase, was not the consequence of an increase in hepatic perfusion, therefore, providing adequate representation of the liver function.

Hepatic hypertrophy and hemodynamics of portal venous flow after percutaneous transhepatic portal embolization

BackgroundPercutaneous transhepatic portal embolization (PTPE) is useful for safe major hepatectomy. This study investigated the correlation between hepatic hypertrophy and hemodynamics of portal venous flow by ultrasound sonography after PTPE.MethodsWe analyzed 58 patients with PTPE, excluding those who underwent recanalization (n = 10). Using CT volumetry results 2 weeks after PTPE, the patients were stratified into a considerable hypertrophy group (CH; n = 15) with an increase rate of remnant liver volume (IR-RLV) ≥ 40% and a minimal hypertrophy group (MH; n = 33) with an IR-RLV < 40%. We investigated the hemodynamics of portal venous flow after PTPE and the favorable factors for hepatic hypertrophy.ResultsUnivariate and multivariate analysis identified the indocyanine green retention rate at 15 min (ICGR15) and increase rate of portal venous flow volume (IR-pFV) at the non-embolized lobe on day 3 after PTPE as independent favorable factors of IR-RLV. Patients with IR-pFV on day 3 after PTPE ≥100% and ICGR15 ≤ 15% (n = 13) exhibited significantly increased IR-RLV compared with others (n = 35).ConclusionsCases with high IR-pFV on day 3 after PTPE exhibited better hepatic hypertrophy. Preserved liver function and increased portal venous flow on day 3 were important.

Portal vein embolization does not result in microvascular flow differences between the embolized and non-embolized liver lobes

Background: Preoperative portal vein embolization (PVE) is used to increase future remnant liver volume enabling extended resections. The microvascular effects occurring after unilateral portal venous occlusion are however, poorly understood. The aim of this study is to assess the microvascular changes in the liver lobes after right PVE. Methods: Videos of the hepatic microcirculation in patients undergoing right hemihepatectomy following PVE were recorded using a handheld intravital microscope, the CytoCam. Hepatic microcirculation was measured in the embolized and the non-embolized lobe after laparotomy. AVA software v. 3.2 was used to obtain the microcirculatory parameters: total vessel density (TVD), microcirculatory flow index (MFI), proportion of perfused vessel (PPV), perfused vessel density (PVD). Results: Five patients were included after PVE (3 males, 2 females, age 66±5 years). TVD and PVD in the non-embolized lobe were significantly increased compared to TVD and PVD in the embolized lobe (i.e. 31.47±2.7 19.7±5.9 mm/mm2P:0.0159). PPV and MFI were not significantly different between the lobes indicating similar microvascular flow despite the difference in vessel density. Conclusion: The non-embolized lobe has a significantly higher microvascular density (TVD and PVD), however without differences in microvascular flow (PPV and MFI). The overall microvascular flow is not affected by PVE which casts doubts on the portal flow differential in inducing the hypertrophy response in the non-embolized lobes.

Functional and volumetric assessment of liver segments after portal vein embolization: Differences in hypertrophy response

Patients considered for liver resection with insufficient volume or function of the future remnant liver are candidates for portal vein embolization to allow safe resection. The aim of this study is to analyze the volumetric and functional responses after portal vein embolization and to evaluate predictors of the hypertrophy response. All patients who underwent portal vein embolization before liver resection 2006-2017 were included. Patients who did not undergo computed tomography-volumetry and functional assessment with technetium-99m mebrofenin hepatobiliary scintigraphy before and after portal vein embolization were excluded. The functional and volumetric response rates were calculated. Multiple regression analysis was conducted to examine the relationship between the hypertrophy response and potential predictors. A total of 90 patients underwent portal vein embolization of the right liver. After 3 weeks, there was a significant increase in both volumetric and functional share of the future remnant liver (both P < .01). The increase in functional share exceeded the increase in volumetric share (P < .01). The median functional contribution of segment 4 after portal vein embolization was 41.5% (31.7%-48.7%) of the nonembolized lobe. Preoperative chemotherapy was not a significant predictor of the increase in function or volume. Compared with benign lesions, malignant diseases were significant negative predictors of the functional response. A total of 3 weeks after portal vein embolization, the functional response exceeded that of the volumetric response, meaning that the waiting time to resection potentially can be decreased. Segment 4 had a significant share of both volume and function, enabling surgical strategies only leaving segment 4 as a monosegment. Neoadjuvant chemotherapy had no negative influence on the hypertrophy response.

The measured hepatic function increase after portal vein embolization measured by 99mTc-mebrofenin hepatobiliary scintigraphy is not attributed by an increased microvascular blood flow

Introduction: Patients scheduled for major liver resection and found unresectable due to insufficient FRL function and volume can undergo portal vein embolization (PVE) to increase resectability. Hereby inducing hypertrophy in the non-embolized lobe with concomitant atrophy in the embolized lobe. The functional gain of the FRL can be assessed with hepatobiliary scintigraphy (HBS). The aim of this study is to determine whether the measured increase in FRL function is the result of an increased hepatic microvascular flow, rather than solely an increase in functional mass by assessing the microcirculatory parameters of both lobes. Methods: Eight patients were included. FRL function was assessed with HBS before and after PVE. During resection, the hepatic microcirculation was assessed with intravital handheld microscope (Cytocam) in both the embolized and non-embolized lobe. Microvascular density parameters (respectively total vascular density (TVD) and perfused vessel density (PVD)) and flow parameters (respectively proportion of perfused vessels (PPV) and red blood cell velocity (RBCv)) were measured. Results: Three weeks after PVE, there was a significant increase function of the non-embolized lobe (P < 0.01). Subsequently, for the microvascular parameters, the non-embolized lobe showed a significantly higher microvascular density (TVD, P < 0.001 and PVD, P < 0.001), without differences in the microvascular flow (PPV, P = 0.43 and RBCv, P = 0.32). Conclusion: This increase in measured hepatic function with HBS after PVE is not attributed by an increase in hepatic microvascular blood flow. This indicates that the measured hepatic function after PVE reflects the increase in hepatic function.

Assessment of hepatic microvascular flow and density in patients undergoing preoperative portal vein embolization

BackgroundThe microvascular effects occurring after unilateral preoperative portal vein embolization (PVE) are poorly understood. The aim of this study was to assess the microvascular changes in the embolized and the non-embolized lobes after right PVE. MethodsVideos of the hepatic microcirculation in patients undergoing right hemihepatectomy following PVE were recorded using a handheld vital microscope (Cytocam) based on incident dark field imaging. Hepatic microcirculation was measured in the embolized and the non-embolized lobes at laparotomy, 3–6 weeks after PVE. The following microcirculatory parameters were assessed: total vessel density (TVD), microcirculatory flow index (MFI), proportion of perfused vessel (PPV), perfused vessel density (PVD), sinusoidal diameter (SinD) and the absolute red blood cell velocity (RBCv). Results16 patients after major liver resection were included, 8 with and 8 without preoperative PVE. Microvascular density parameters were higher in the non-embolized lobes when compared to the embolized lobes (TVD: 40.3 ± 8.9 vs. 26.8 ± 4.6 mm/mm2 (p < 0.003), PVD: 40.3 ± 8.8 vs. 26.7 ± 4.7 mm/mm2 (p < 0.002), SinD: 9.2 ± 1.7 vs. 6.3 ± 0.8 μm (p < 0.040)). RBCv, PPV and the MFI were not significantly different. ConclusionThe non-embolized lobe has a significantly higher microvascular density, however without differences in microvascular flow. These findings indicate increased angiogenesis in the hypertrophic lobe.

Application value of dynamic SPECT 99Tcm-GSA scintigraphy assessing regional liver function changes before and after portal vein embolization

Objective To investigate the application value of dynamic single-photon emission computed tomography (SPECT) 99m-technetium galactosyl human serum albumin diethylenetriamine pentaacetic acid injection (99Tcm-GSA) scintigraphy assessing regional liver function changes before and after portal vein embolization (PVE). Methods The retrospective cross-sectional study was conducted. The clinical data of 11 patients with Bismuth Ⅲa hilar cholangiocarcinoma who were admitted to the General Hospital of People′s Liberation Army (10 patients) and Beijing Tsinghua Changgung Hospital (1 patient) from October 2010 to October 2016 were collected. B ultrasound-guided percutaneous transhepatic ipsilateral exbolization was performed before radical resection of hilar cholangiocarcinoma. Dynamic SPECT 99Tcm-GSA scintigraphy was performed to calculate and compare the changes of functional liver volume (FLV), morphological liver volume (MLV) and functional liver density (FLD) in embolized lobe and non-embolized lobe before PVE and 2 weeks after PVE. Observation indicators: (1) the changes of serum indexes in 2 weeks before and after PVE; (2) the changes of FLV, MLV and FLD in the whole liver, embolized and non-embolized lobes in 2 weeks before and after PVE; (3) surgical and postoperative situations of hilar cholangiocarcinoma; (4) follow-up and survival situations. Follow-up using outpatient examination and telephone interview was performed to detect postoperative serum toal bilirubin (TBil) level, with or without peritoneal effusion and survival up to June 2017. Measurement data with normal distribution were represented as ±s. The comparisons of pre-and post-operative data were analyzed by the paired t test. Results (1) The changes of serum indexes in 2 weeks before and after PVE: 11 patients underwent successful right PVE. The alanine aminotransferase (ALT), TBil, albumin (Alb), Platelets (PLT) and prothrombin time (PT) were respectively (113±20)U/L, (73±8)μmol/L, (35.0±2.5)g/L, (209±58)×109/L, (11.4±0.7)seconds in 2 weeks before PVE and (120±18)U/L, (36±7)μmol/L, (34.4±3.2)g/L, (224±82)×109/L, (11.2±0.8)seconds in 2 weeks after PVE, with a statistically significant difference in TBil level (t=-10.592, P 0.05). (2) The changes of FLV, MLV and FLD in the whole liver, embolized and non-embolized lobes in 2 weeks before and after PVE: the FLV, MLV and FLD of the whole liver were respectively (894±255)mL, (1 552±504)mL, 0.59±0.14 in 2 weeks before PVE and (812±206)mL, (1 521±422)mL, 0.55±0.16 in 2 weeks after PVE, with no statistically significant difference (t=1.569, 0.666, 1.980, P>0.05). The FLV, MLV and FLD of the embolized lobe were respectively (623±275)mL, (1 047±394)mL, 0.62±0.14 in 2 weeks before PVE and (375±240)mL, (865±337)mL, 0.44±0.24 in 2 weeks after PVE, with statistically significant differences (t=5.909, 3.736, 3.359, P<0.05); the descending percentages were respectively 38.1%, 9.8% and 24.6%. The FLV, MLV and FLD of the non-embolized lobe were respectively (274±152)mL, (530±176)mL, 0.52±0.21 in 2 weeks before PVE and (436±149)mL, (656±133)mL, 0.68±0.24 in 2 weeks after PVE, with statistically significant differences (t=-6.019, -6.345, -3.933, P<0.05); the elevated percentages were respectively 80.1%, 19.9% and 23.8%. (3) Surgical and postoperative situations of hilar cholangiocarcinoma: of 11 patients, 10 received successful peri-hilar right hemihepatectomy, the right hepatic atrophy and an obvious demarcation line between left and right liver were found intraoperatively; 1 stopped operation due to detect intraoperatively peritoneal metastasis of tumor. The operation time, volume of intraoperative blood loss and time of postoperative abdominal drainage-tube removal were respectively (585±194)minutes, (472±274)mL and (8±5)days. Of 10 patients undergoing operations, 2 were complicated with massive peritoneal effusion at 2 days postoperatively, volume of peritoneal effusion remained more than 500 mL up to 7 days after drainage, and were improved by 1- month conservative treatment; other 8 patients were not complicated with hepatic dysfunction. Duration of hospital stay of 11 patients was (16±4)days. (4) Follow-up and survival situations: 10 patients were followed up for 4-72 months, with a median time of 39 months. During the follow-up, there was no evaluated TBil level and peritoneal effusion in 10 patients. The median survival time, 1-, 3- and 5-year overall survival rates were 88.8%, 74.6% and 36.8%, respectively. Conclusions The dynamic SPECT 99Tcm-GSA scintigraphy can effectively evaluate liver function changes of embolized and non-embolized lobes before and after PVE. The increased rate of FLV of non-embolized lobe is higher than that of MLV. Key words: Hilar cholangiocarcinoma; Radical resection; Portal vein embolization; Scintigraphy single-photon emission computed tomography; 99m-technetium galactosyl human serum albumin diethylenetriamine pentaacetic acid injection; Regional liver function

Liver atrophy after percutaneous transhepatic portal embolization occurs in two histological phases: Hepatocellular atrophy followed by apoptosis.

AIMTo clarify the histological changes associated with liver atrophy after percutaneous transhepatic portal embolization (PTPE) in pigs and humans.METHODSAs a preliminary study, we performed pathological examinations of liver specimens from five pigs that had undergone PTPE in a time-dependent model of liver atrophy. In specimens from embolized lobes (EMB) and nonembolized lobes (controls), we measured the portal vein to central vein distance (PV-CV), the area and number of hepatocytes per lobule, and apoptotic activity using the terminal deoxynucleotidyl transferase dUTP nick-end labeling assay. Immunohistochemical reactivities were evaluated for light chain 3 (LC3) and lysosomal-associated membrane protein 2 (LAMP2) as autophagy markers and for glutamine synthetase and cytochrome P450 2E1 (CYP2E1) as metabolic zonation markers. Samples from ten human livers taken 20-36 d after PTPE were similarly examined.RESULTSPV-CVs and lobule areas did not differ between EMB and controls at day 0, but were lower in EMB than in controls at weeks 2, 4, and 6 (P ≤ 0.001). Hepatocyte numbers were not significantly reduced in EMB at day 0 and week 2 but were reduced at weeks 4 and 6 (P ≤ 0.05). Apoptotic activity was higher in EMB than in controls at day 0 and week 4. LC3 and LAMP2 staining peaked in EMB at week 2, with no significant difference between EMB and controls at weeks 4 and 6. Glutamine synthetase and CYP2E1 zonation in EMB at weeks 2, 4, and 6 were narrower than those in controls. Human results were consistent with those of porcine specimens.CONCLUSIONThe mechanism of liver atrophy after PTPE has two histological phases: Hepatocellular atrophy is likely caused by autophagy in the first 2 wk and apoptosis thereafter.

Limits of and Complications after Embolization of the Hepatic Artery and Portal Vein to Induce Segmental Hypertrophy of the Liver: A Large Mini-Pig Study

Background: The aim of this study was to compare arterial embolization (AE) with portal vein embolization (PVE) for the induction of segmental hypertrophy regarding procedural efficacy, safety and outcome. Methods: A total of 29 mini pigs were subjected to PVE, AE or assigned to the sham (SO) group. Correspondingly, 75% of the hepatic artery or portal vein branches were embolized. Growth and atrophy of the liver lobes, calculating the liver-to-body weight index (LBWI), laboratory data, arteriography, portography, Doppler ultrasound (US) and histopathology were analyzed. Results: After PVE, 2 animals had to be excluded due to technical problems. After AE, 4 animals had to be excluded because of technical problems and early sacrifice. Postprocedural US demonstrated effective AE and PVE of the respective lobes. Four weeks after PVE, portography showed a slow refilling of the embolized lobe by collateral portal venous vessels. Four weeks after AE, arteriography revealed a slight revascularization of the embolized lobes by arterial neovascularization. Segmental AE led to extensive necrotic and inflammatory alterations in the liver and bile duct parenchyma. Significant hypertrophy of the non-embolized lobe was only noted in the PVE group (LBWI: 0.91 ± 0.28%; p = 0.001). There was no increase in the non-embolized lobe in the AE (LBWI: 0.45 ± 0.087%) and SO group (LBWI: 0.45 ± 0.13%). Conclusion: PVE is safe and effective to induce segmental hypertrophy. Portal reperfusion by collateral vessels may limit hypertrophy. AE did not increase the segmental hepatic volume but carries the risk of extensive necrotic inflammatory damage.

Preoperative Sequential Portal and Hepatic Vein Embolization in Patients with Hepatobiliary Malignancy.

Preoperative portal vein embolization (PVE) induces shrinkage of the embolized lobe and compensatory regeneration in the non-embolized lobe, but does not always induce sufficient regeneration of the future remnant liver (FRL). We previously developed preoperative sequential PVE-hepatic vein embolization (HVE), and here we present our experience of treating 42 patients with sequential PVE-HVE. During 8-year study period, preoperative PVE-HVE was performed on 42 patients with hepatobiliary malignancies. Primary diseases were bile duct cancers [perihilar cholangiocarcinoma (n = 33) and diffuse bile duct cancer (n = 1)], hepatocellular carcinomas (n = 4), and intrahepatic tumors [intrahepatic cholangiocarcinoma (n = 3) and gallbladder cancer liver invasion (n = 1)]. These patients demonstrated insufficient FRL regeneration following PVE, thus HVE was performed to induce further regeneration. No PVE-HVE procedure-associated complications occurred. In the bile duct cancer group, FRL volume was 33.9 ± 2.2 % before PVE, 38.4 ± 1.5 % before HVE, 43.7 ± 2.1 % at surgery, and 73.6 ± 8.3 % at 2 weeks after right hepatectomy. The degree of FRL hypertrophy was 13.3 % after PVE, 28.9 % after PHV-HVE, and 117.1 % at 2 weeks after right hepatectomy. All patients except one recovered uneventfully after surgery, and the 3-year patient survival rate was 45.1 %. In the HCC group, transarterial chemoembolization was initially performed and FRL regeneration following PVE-HVE occurred very slowly. Active FRL regeneration occurred in the liver tumor group, but rapid tumor growth was observed in 1 of 4 patients. The sequential application of HVE following PVE safely and effectively induces further FRL regeneration in non-cirrhotic livers. Further validation using larger patient population and multicenter studies is needed to reliably widen the indications.

Tumour growth after portal vein embolization with pre-procedural chemotherapy for colorectal liver metastases

BackgroundFor resection of colorectal cancer (CRC) liver metastases, pre-operative portal vein embolization (PVE) is used to increase the size of the future liver remnant (FLR) prior to advanced liver resection when indicated. PVE is speculated to cause tumour progression, but only a limited number of studies have analysed tumour growth after PVE in the context of pre-procedural chemotherapy, which was the aim of this retrospective study. MethodsPatients treated with stabilizing chemotherapy and PVE before liver resection for CRC metastases were included. Tumour progression according to RECIST guidelines and a change in tumour volume was analysed on computed tomography (CT) scans prior to chemotherapy, before PVE and after PVE, respectively. ResultsThirty-four patients were included, of whom 23 had bilobar disease. Of tumours in the embolized lobe, 3/34 showed progression after PVE as compared with 3/23 in the non-embolized lobe (P = 0.677). A decrease in tumour volume of 16% and 11% was noted in the embolized and non-embolized lobe, respectively (P = 0.368). Patients were off chemotherapy in a median of 16 days before PVE. There was a linear correlation between the growth of tumours and time between the end of chemotherapy and PVE (r = 0.25, P = 0.0005). ConclusionThe rate of progression of CRC liver metastases after PVE and pre-procedural chemotherapy was lower in the present study as compared with previous reports. This applies to tumours in both the embolized and non-embolized lobes and is associated with keeping the time between the end of chemotherapy and PVE short.

The adverse effects of preoperative cholangitis on the outcome of portal vein embolization and subsequent major hepatectomies

The presence of cholangitis has been shown to impair liver regeneration capacity after major hepatectomy in a rat cholangitis model. It is unclear, however, whether the presence of cholangitis has any impact on liver generation in clinical settings. To determine the effects of preoperative cholangitis on hepatic regeneration rates after preoperative portal vein embolizations (PVEs) and postoperative courses after major hepatectomies in humans. From 1991 to 2012, 450 patients underwent preoperative PVEs and subsequent major hepatectomies. Among them, 72 patients (16.0%) had preoperative cholangitis. The volume change of the nonembolized lobe after PVE and the postoperative outcomes after a major hepatectomy were compared between cholangitis and noncholangitis groups. The average volume increase in the nonembolized lobe after PVE was almost identical in both the cholangitis (10.0%) and noncholangitis (9.5%) groups. The average term required to acquire institutional safety criteria, however, was longer in the cholangitis group (24.3 days) compared with the noncholangitis group (18.3 days) (P < .001). The postoperative maximum serum total bilirubin levels (5.7 mg/dL vs 8.1 mg/dL, P = .035), morbidity rate (56% vs 78%, P = .001), and postoperative hospital stay (44 days vs 53 days, P = .021) were all greater in the cholangitis group compared with the noncholangitis group. With multivariate logistic regression analyses, the presence of preoperative cholangitis was identified as one of the independent risk factors for postoperative morbidity. These results indicate that patients with preoperative cholangitis should be carefully managed during their perioperative periods of PVE and after major hepatectomies.

Portal vein embolization using absolute ethanol: evaluation of its safety and efficacy

Previously, we reported on the clinical efficacy and safety of portal vein embolization (PVE) with fibrin glue. Our embolic materials for PVE changed from fibrin glue to absolute ethanol (EOH) after 2001 due to prohibition of using fibrin glue for PVE. With introducing our technique of PVE with EOH, we evaluated its safety and efficacy with attention to the amount of EOH. The medical records of 154 patients who underwent PVE using EOH were retrospectively reviewed. Changes with time in both the serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) after PVE returned to the initial condition within 7 days after PVE. In the 96 patients who underwent CT volumerty 14 to 21 days after PVE, the volume of the embolized lobe decreased from 701 ± 165 cm(3) to 549 ± 148 cm(3) (P < 0.0001). Meanwhile, the volume of the non-embolized lobe increased from 388 ± 105 cm(3) to 481 ± 113 cm(3) (P < 0.0001). On simple linear regression, the amount of EOH was positively correlated with both the maximum of AST and that of ALT after PVE; however, it never correlated with changes in liver volume after PVE. Portal vein embolization with EOH has a substantial effect on both hypertrophy of the non-embolized lobe and atrophy of the embolized lobe. Quick recoveries of changes with time in AST and ALT after PVE proved that PVE with EOH is a safe procedure. The amount of EOH affected the extent of liver damage but had no clinical effects on changes in liver volume after PVE.

NF-E2-related factor 2 promotes compensatory liver hypertrophy after portal vein branch ligation in mice

Hepatectomy is a standard therapy that allows liver cancer patients to achieve long-term survival. Preceding hepatectomy, portal vein embolization (PVE) is frequently performed to increase the remnant liver size and reduce complications. Although the clinical importance of PVE is widely accepted, molecular mechanisms by which PVE leads to compensatory hypertrophy of nonembolized lobes remain elusive. We hypothesized that NF-E2-related factor 2 (Nrf2), a master regulator of cytoprotection, promotes compensatory liver hypertrophy after PVE. To address this hypothesis, we utilized three mouse lines and the portal vein branch ligation (PVBL) technique, which primarily induces the redistribution of the portal bloodstream in liver in a manner similar to PVE. PVBL was conducted in Kelch-like ECH-associated protein 1 (Keap1) conditional knockout (Keap1-CKO) mice in which Nrf2 is constitutively activated, along with Nrf2-deficient (Nrf2-KO) mice. We found that hypertrophy of nonligated lobes after PVBL was enhanced and limited in Keap1-CKO and Nrf2-KO mice, respectively, compared to wild-type mice. In Keap1-CKO mice, Nrf2 activity was increased, consistent with transient activation of the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway, and reactive hepatocyte proliferation was significantly prolonged after PVBL. Importantly, Nrf2 activation by a chemical inducer was also effective for enhancement of hypertrophy after PVBL. Nrf2 supports compensatory liver hypertrophy after PVBL. This finding is particularly intriguing, because the primary effect of PVBL is limited to the alteration of bloodstream; this effect is much milder than changes resulting from hepatectomy, in which intrahepatic bloodstream and bile production cease. Our results suggest that premedication with an Nrf2 inducer may be a promising strategy to improve the outcome of PVE; this approach expands the indication of hepatectomy to patients with poorer liver function.

Colorectal liver metastases growth in the embolized and non-embolized liver after portal vein embolization: influence of initial response to induction chemotherapy.

To compare tumor progression in both embolized and non-embolized liver lobes after portal vein embolization (PVE) in patients with bilobar colorectal liver metastases (CLM), according to the initial response to induction chemotherapy. From 2002 to 2012, a total of 42 consecutive patients with bilobar CLM initially treated using induction chemotherapy underwent right PVE to achieve adequate future liver remnant volume. Tumoral and liver parenchyma volumes, as well as their volume variations, were measured on computed tomography before and after PVE in both embolized and non-embolized. Patients were classified as fast (≤6 cycles of induction chemotherapy) and slow (>6 cycles) responders. Overall, 432 metastases were analyzed in 42 patients. Patients were slow responders in 29 (69 %) cases. Tumoral volume increased in 29 (69 %) cases in the embolized liver (+48 %; p < 0.0001), and in 28 (66 %) cases in the non-embolized liver (+31 %; p < 0.0001). Fast responders had a tumoral volume decrease in both embolized (-4 %) and non-embolized (-9 %) lobes. On the opposite side, slow responders had tumoral volume increase in both embolized (+79 %) and non-embolized (+32 %) lobes. On multivariate analysis, a 'slow' response to induction chemotherapy was the only factor associated with tumoral progression in both embolized (p = 0.0012) and non-embolized (p = 0.001) lobes. Tumor growth after PVE is observed in both embolized and non-embolized liver lobes in most patients but is significantly associated with slow response to induction chemotherapy.