Nonembolized Liver Lobe Research Articles

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.

Dynamic Contrast-Enhanced MR Imaging Evaluation of Perfusional Changes and Ablation Zone Size after Combination Embolization and Ablation Therapy

PurposeThe objectives of this study were to assess the utility of dynamic contrast-enhanced magnetic resonance (MR) imaging in quantifying parenchymal perfusional changes after embolization and to characterize the association between pharmacokinetic (PK) parameters and final microwave ablation volume. Materials and MethodsPK parameters from dynamic contrast-enhanced MR imaging were used to quantify perfusional changes in the liver after transarterial embolization of the right or left lobe in a swine liver model (n = 5). Each animal subject subsequently underwent microwave ablation (60 W for 5 minutes) of the embolized and nonembolized liver lobes. Changes in PK parameters from dynamic contrast-enhanced MR imaging were correlated with their respective final microwave ablation volumes in each liver lobe. ResultsMicrowave ablation volumes of embolized liver lobes were significantly larger than those of nonembolized liver lobes (28.0 mL ± 6.2 vs 15.1 mL ± 5.2, P < .001). PK perfusion parameters were significantly lower in embolized liver lobes than in nonembolized liver lobes (Ktrans = 0.69 min−1 ± 0.15 vs 1.52 min−1 ± 0.37, P < .001; kep = 0.69 min−1 ± 0.19 vs 1.54 min−1 ± 0.42, P < .001). There was a moderate but significant correlation between normalized kep and ablation volume, with each unit increase in normalized kep corresponding to a 9.8-mL decrease in ablation volume (P = .035). ConclusionsPK-derived parameters from dynamic contrast-enhanced MR imaging can be used to quantify perfusional changes after transarterial embolization and are directly inversely correlated with final ablation volume.

Expression of MMP-2 in residual VX2 liver tumor after transcatheter arterial embolization combined with portal venous embolization in an animal model

ObjectiveThis study aimed to analyze the effects of transcatheter arterial embolization (TAE) combined with portal venous embolization (PVE) on the expression of MMP-2 in residual VX2 liver tumor tissues, liver function and non-embolic lobe regeneration. MethodsA total of 72 rabbits were randomly divided into Sham, TAE, PVE and TAE ​+ ​PVE groups (n ​= ​18/group). The tissue samples from each group were taken at 6 ​h, 3 days and 7 days after interventional operation, respectively. MMP-2 expression was detected by immunohistochemistry, Real-time PCR, and Western-blotting. The main indicators (such as AST, ATL, and TBIL) of liver function and the volume of non-embolized hepatic lobes were measured in each group after operation. One-way ANOVA and Kruskal-wallis method were used for statistical analysis. ResultsThe expression of MMP-2 mRNA and protein remained the highest in the Sham group, and the expression of MMP-2 mRNA and protein in TAE, PVE and TAE ​+ ​PVE groups were successively increased, and the expression of MMP-2 in TAE ​+ ​PVE group was always significantly higher than TAE group. The AST and ALT levels in each group on day 7 after operation showed a significant declination, and all groups have recovered to the preoperative baseline level and TBIL has a slight fluctuation in each group after operation with no statistical difference. On day 7 after operation, the increasing volume of non-embolized liver lobes in TAE ​+ ​PVE group showed a more significant effect than those in PVE group, but there was no statistical significance (37.62 ​± ​1.54 ​ml VS 36.18 ​± ​1.15 ​ml, P ​= ​0.881), and its volume was significantly higher than those in the sham group (27.03 ​± ​1.11 ​ml). ConclusionTAE ​+ ​PVE is considered to be an efficient and safe approach for treating rabbit VX2 liver transplantation tumor, but the expression of MMP-2 increased fastest after TAE ​+ ​PVE, which might promote tumor cell invasion and metastasis.

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.

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.

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

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

Hepatic parenchymal transection increases liver volume but not function after portal vein embolization in rabbits

Associating liver partition with portal vein ligation for staged hepatectomy induces more extensive liver hypertrophy than ligation alone; however, the mechanisms underlying the accelerated liver regrowth and the functional quality of the hypertrophic liver are presently elusive. This study, therefore, investigated the effect of parenchymal transection on liver volume and function after portal vein embolization in a standardized rabbit model. Twelve rabbits were subjected to portal vein embolization of the cranial liver lobes and randomized between parenchymal transection of the left lateral liver lobe versus no transection (portal vein embolization only). Liver volume of the nonembolized liver lobe was assessed using computed tomography-volumetry, and liver uptake function was determined by 99mTc-mebrofenin hepatobiliary scintigraphy before and 3 and 7days after portal vein embolization. The increase in nonembolized liver volume 3days after portal vein embolization was 2.7-fold greater in the transected group compared with the portal vein embolization only group (56 ±16% vs 21 ±12%, respectively, P<.01) and 1.7-fold greater 7days after portal vein embolization (113 ±34% vs 68 ±24%, P<.01). Liver uptake function did not differ between groups before portal vein embolization (8.4 ±3.7%/min in the transection group vs 8.9 ±1.6%/min) on day 3 (33.2 ±4.7% after transection vs 30.3 ±4.6%/min, respectively) and day 7 after portal vein embolization (42.6 ±8.4% vs 39.1 ±5.3%/min, respectively). Parenchymal transection after portal vein embolization increases liver growth in terms of volume but not function. These results indicate that the rapid volume increase observed after associating liver partition with portal vein ligation for staged hepatectomy does not coincide with the clinically more relevant functional increase. Quantitative liver function tests might be essential in associating liver partition with portal vein ligation for staged hepatectomy to better assess the hypertrophy response and improve clinical decision-making.

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.

Enhanced tumor growth after portal vein embolization in a rabbit tumor model

BackgroundPreoperative portal vein embolization (PVE) is used to increase future remnant liver volume through induction of hepatocellular regeneration. This event, however, potentially enhances tumor growth. The aim of our study was to assess tumor growth and liver regeneration after PVE in a rabbit hepatic tumor model. The VX2 carcinoma is derived from a virus-induced papilloma tumor in rabbits. The tumor grows rapidly, and its blood supply is similar to that of human hepatocellular carcinoma. Materials and methodsTwo weeks after subcapsular implantation of a VX2 carcinoma in the cranial liver lobe, New Zealand White rabbits were allocated to a control or PVE group (n = 5 per group). In the PVE group, the portal vein branch to the cranial liver lobes (80%) was embolized using particles and coils, leaving the caudal liver lobe (20%) free. In the tumor control group, the liver was mobilized. Computed tomography volumetry was performed on days 3, 7, 10, and 14. Tumor growth rate (TGR), hepatocellular proliferation rate, and liver damage parameters were assessed before PVE and on days 1, 3, 7, 10, and 14. ResultsPortography confirmed complete occlusion of the portal vein branch to the cranial liver lobes in all PVE rabbits. The hypertrophy response and proliferation rate in the nonembolized liver lobes were significantly higher in the PVE group, which was confirmed by liver-to-body weight index assessment. TGR was increased in both groups, with a significantly larger increase in the PVE group over time (day 14: mean, 34.4 ± 4.3 mL/d versus control: mean, 24.1 ± 7.2 mL/d; P < 0.05). ConclusionsTGR was significantly increased after PVE in the rabbit tumor model. This finding supports the notion that PVE potentially enhances tumor growth, along with the regeneration of the nonembolized liver lobe.

Bile salts predict liver regeneration in rabbit model of portal vein embolization

BackgroundPortal vein embolization (PVE) is employed to increase future remnant liver (FRL) volume through induction of hepatocellular regeneration in the nonembolized liver lobe. The regenerative response is commonly determined by CT volumetry after PVE. The aim of the study was to examine plasma bile salts and triglycerides in the prediction of the regenerative response following PVE. MethodsPVE of the cranial liver lobe was performed in 15 rabbits, divided into three groups: NaCl (control), gelatin sponge (short-term occlusion), and polyvinyl alcohol particles with coils (PVAc, long-term occlusion). In all rabbits CT volumetry and blood sampling were performed prior to PVE and on days 3 and 7. Plasma bile salts and triglycerides were correlated with volume increase of the nonembolized liver lobe. ResultsAfter 3 and 7 d, respectively, FRL volume was increased in both embolized groups, with the largest hypertrophy response observed in the PVAc group. Plasma bile salt levels were increased after PVE, especially in the PVAc group at day 3 (P < 0.01 compared to gelatin sponge). Plasma bile salts at day 3 predicted FRL volume increase at day 7 showing a positive correlation of 0.811 (P < 0.001). Levels of triglycerides were not significantly altered in either of the PVE procedures. ConclusionsPlasma bile salt levels early after PVE strongly correlated with the regenerative response in a rabbit model of PVE, showing more pronounced elevation with larger volume increase of the nonembolized lobe. Therefore, plasma bile salts, but not triglycerides, can be used in the prediction of the regenerative response after PVE.

Percutaneous preoperative portal vein embolization using a combination of gelatin sponge and histoacryl glue

Inadequate remnant liver volume is a major cause of postoperative liver failure. Preoperative portal vein embolization (PVE) is used clinically to prevent postoperative liver insufficiency. To evaluate the efficacy and safety of preoperative portal vein embolization, by using a combination of gelatin sponge and histoacryl to induce hypertrophy of future liver remnant (FLR) in patients with a hepatobiliary malignancy. PVE using a combination of gelatin sponge and histoacryl glue was performed in 11 patients (nine men, two women; mean age 60 years, range 46-70 years). These patients were diagnosed with a hepatobiliary malignancy before surgery and their FLR volumes were judged as insufficient to allow for safe resection (FLR <25% in patients with a normal liver or FLR <40% in patients with a chronic liver disease). Liver volume changes, levels of biochemical markers, complications related to PVE, and postoperative complications were retrospectively evaluated. PVE was successful in all patients, and there were no procedural complications. The enlargement of nonembolized liver lobe was 30% (mean 118 cm3). A planned hepatectomy was cancelled in four patients due to the presence of a late-detected extrahepatic metastasis. Seven of the 11 patients underwent hepatectomy without complications. Preoperative PVE with a combination of gelatin sponge and histoacryl glue is a safe and effective procedure to induce hypertrophy of nonembolized parts of the liver.

Induction of Tumor Growth After Preoperative Portal Vein Embolization: Is It a Real Problem?

Although preoperative portal vein embolization (PVE) is an effective means to increase future remnant liver (FRL) volume, little has been published on possible adverse effects. This review discusses the clinical and experimental evidence regarding the effect of PVE on tumor growth in both embolized and nonembolized liver lobes, as well as potential strategies to control tumor progression after PVE. A literature review was performed using MEDLINE with keywords related to experimental and clinical studies concerning PVE, portal vein ligation (PVL), and tumor growth. Cross-references and references from reviews were also checked. Clinical and experimental data suggest that tumor progression can occur after preoperative PVE in embolized and nonembolized liver segments. Clinical evidence indicating possible tumor progression in patients with colorectal metastases or with primary liver tumors is based on studies with small sample size. Although multiple studies demonstrated tumor progression, evidence concerning a direct increase in tumor growth rate as a result of PVE is circumstantial. Three possible mechanisms influencing tumor growth after PVE can be recognized, namely changes in cytokines or growth factors, alteration in hepatic blood supply and an enhanced cellular host response promoting local tumor growth after PVE. Post-PVE chemotherapy and sequential transcatheter arterial chemoembolization (TACE) before PVE have been proposed to reduce tumor mass after PVE. We conclude that tumor progression can occur after PVE in patients with colorectal metastases as well as in patients with primary liver tumors. However, further research is needed in order to rate this risk of tumor progression after PVE.

Type IV Collagen 7s Domain as a Predictor of Poor Efficacy of Portal Vein Embolization Before Major Hepatectomy

We investigated the correlation between serum concentrations of type IV collagen 7s domain (7s collagen) and changes in the volume of the nonembolized liver lobe after subsequent portal vein embolization (PVE). The relationship between the pre-embolization results of laboratory tests and the increase in the left lobe volume was evaluated in 32 patients who underwent preoperative PVE via the right portal vein. By 2 weeks after PVE, the mean volume of the left lobe had increased significantly (P < 0.001). The percent increase in the left lobe volume correlated negatively with the pre-embolization serum concentration of 7s collagen (r = -0.472, P = 0.0063). In three of four patients with high serum concentrations (>8 ng/ml), the percent increase was less than 100% and right lobectomy was not performed. The serum 7s collagen concentration correlated with the histologic activity score (r = 0.469, P = 0.0061) and the histologic fibrosis score (r = 0.425, P = 0.0145). The serum concentration of 7s collagen may predict the efficacy of PVE. Performing PVE before right lobectomy may not be indicated in patients with high serum concentrations of 7s collagen because the increases in left lobe volume may be insufficient.

Effect of Preoperative Portal Vein Embolization on Liver Volume and Hepatic Energy Status of the Nonembolized Liver Lobe in Humans

Clinically portal vein embolization (PVE) is presently preferred to extended hepatectomy. Nevertheless, its effect on hepatic adenosine triphosphate (ATP) and energy charge levels, which are essential for organ viability, has been little studied in humans. Fourteen patients with (n = 7) and without (n = 7) preoperative right PVE participated in this study. Changes in hepatic lobar volume and serum liver function tests were examined before and after percutaneous transhepatic right PVE. Liver volume (cm³) was calculated on computed tomograms before and 20 ± 3 days after PVE. At the time of surgery (mean of 25 days after PVE), small liver specimens were obtained from portal vein (PV) nonembolized left lobes immediately after laparotomy without any ischemic procedures. Concentrations of adenine nucleotides were measured by high performance liquid chromatography, and hepatic energy charge levels were calculated. These values were compared with those in control patients who had not undergone preoperative PVE. Serum liver function tests including the indocyanine green retention rate did not differ significantly before and after PVE. The volume of the PV-nonembolized left lobe significantly increased after right PVE (from 473 ± 32 to 624 ± 66 cm³), with a significant increase in the percentage of the left lobe to total liver volume. The concentrations of AMP, ADP, and ATP, and hepatic energy charge levels in the PV-nonembolized left lobe were similar to those of the control liver. These results suggest that preoperative right PVE increases the volume of the nonembolized left lobe, keeping the hepatic engery charge and ATP levels similar to the control liver, thereby increasing the total amount of ATP and hepatic energy reserve of the PV-nonembolized lobe in proportion to its volume increase at the time of surgery.