Size Of Future Liver Remnant Research Articles

Liver remnant volume to body weight ratio of 0.65% as a lower limit in right hepatic trisectionectomy with bile duct resection

BackgroundPrevious studies have suggested the utility of an indocyanine green plasma clearance rate of the future liver remnant (FLR) (ICGK-F) ≥0.05 in hepatobiliary resection to reduce the surgical risk. The present study aimed to verify whether future liver remnant size rather than ICGK-F matters in extended hepatobiliary resection. MethodsBetween 2004 and 2021, patients who underwent right hepatic trisectionectomy with bile duct resection were included. The effect of the FLR volume-to-body weight ratio (FLR/BW) and ICGK-F on posthepatectomy liver failure was evaluated along with other parameters. ResultsAmong 91 study patients, the median ICGK-F, FLR, and FLR/BW were 0.057 (range, 0.027–0.099), 392 mL (145–705), and 0.78% (0.40–1.37), respectively. Posthepatectomy liver failure occurred in 23 patients. The incidence was 10 (40%) in 25 patients with an ICGK-F <0.05 and 12 (18%) in 65 patients with an ICGK-F ≥0.05 (P = .053); 13 (52%) in 25 patients with a FLR/BW <0.65% and 10 (15%) in 66 patients with a FLR/BW ≥0.65% (P = .001). Multivariate analysis showed that a FLR/BW <0.65% (odds ratio, 11.7; P = .005), age ≥65 years (odds ratio, 31.7; P < .001), and blood loss ≥25 mL/kg (odds ratio, 22.1; P = .004) were independent predictors of posthepatectomy liver failure, but ICGK-F <0.05 was not (P = .499). According to the meeting number of 3 factors, posthepatectomy liver failure incidence was 0 of 22 (0%) in patients with 0 factors, 6 of 43 (14%) in patients with 1, and 17 of 26 (65%) in patients with 2 or 3 (P < .001). ConclusionA FLR/BW ≥0.65% may serve as a volumetric basis to reduce posthepatectomy liver failure after extended hepatobiliary resection.

Portal Vein Embolization for Hepatocellular Carcinoma: A Propensity Score Matching Analysis

Introduction: Portal vein embolization (PVE) increased the size of future liver remnant (FLR) which allowed patients became operable due to inadequate volume. The aim of the study is to review the outcome of patients who had undergone PVE and hepatectomy for hepatocellular carcinoma (HCC).

Simulated model of RAPID concept: highlighting innate inflammation and liver regeneration.

BackgroundThe resection and partial liver segment II/III transplantation with delayed total hepatectomy (RAPID) concept is a novel transplantation technique for removal of non‐resectable liver tumours. The aim of this study was to establish a simulated RAPID model to explore the mechanism involved in the liver regeneration.MethodsA RAPID model was created in rats involving cold ischaemia and reperfusion of the selected future liver remnant (FLR), portal vein ligation, followed by resection of the deportalized lobes in a second step. Histology, liver regeneration and inflammatory markers in RAPID‐treated rats were compared with those in controls that underwent 70 per cent hepatectomy with the same FLR size. The effects of interleukin (IL) 6 and macrophage polarization on hepatocyte viability were evaluated in an in vitro co‐culture system of macrophages and BRL hepatocytes.ResultsThe survival rate in RAPID and control hepatectomy groups was 100 per cent. The regeneration rate was higher in the RAPID‐treated rats, with higher levels of IL‐6 and M1 macrophage polarization (P < 0·050). BRL hepatocytes co‐cultured with M1 macrophages showed a higher proliferation rate through activation of the IL‐6/signal transducer and activator of transcription 3/extracellular signal‐regulated kinase pathway. This enhancement of proliferation was inhibited by tocilizumab or gadolinium trichloride (P < 0·050).ConclusionThe surgical model provides a simulation of RAPID that can be used to study the liver regeneration profile. Surgical RelevanceThe mechanisms sustaining liver regeneration are a relevant field of research to reduce the ‘small for size’ liver syndrome when the future liver remnant is not adequate. Several surgical strategies have been introduced both for liver resection and transplant surgery, mostly related to this issue and to the scarcity of grafts, among these the RAPID concept involving the use of an auxiliary segment II/III donor liver that expands to a sufficient size until a safe second‐stage hepatectomy can be performed. Understanding the mechanisms and pitfalls of the liver regeneration profile may help in tailoring surgical strategies and in selecting patients. In this experimental model the authors investigated liver histology, regeneration and inflammatory markers in RAPID‐treated rats.

Segment 4 occlusion in portal vein embolization increase future liver remnant hypertrophy - A Scandinavian cohort study.

The additional value of including segment 4 (S4) portal branches in right portal vein embolization (rPVE) is debated. The aim of the study was to explore this in a large multicenter cohort. A retrospective cohort study consisting of all patients subjected to rPVE from August 2012 to May 2017at six Scandinavian university hospitals. PVE technique was essentially the same in all centers, except for the selection of main embolizing agent (particles or glue). All centers used coils or particles to embolize S4 branches. A subgroup analysis was performed after excluding patients with parts of or whole S4 included in the future liver remnant (FLR). 232 patients were included in the study, of which 36 received embolization of the portal branches to S4 in addition to rPVE. The two groups (rPVE vs rPVE+S4) were similar (gender, age, co-morbidity, diagnosis, neoadjuvant chemotherapy, bilirubin levels prior to PVE and embolizing material), except for diabetes mellitus which was more frequent in the rPVE+S4 group (p=0.02). Pre-PVE FLR was smaller in the S4 group (333 vs 380ml, p=0.01). rPVE+S4 resulted in a greater percentage increase of the FLR size compared to rPVE alone (47 vs 38%, p=0.02). A subgroup analysis, excluding all patients with S4 included in the FLR, was done. There was no longer a difference in pre-PVE FLR between groups (333 vs 325ml, p=0.9), but still a greater percentage increase and also absolute increase of the FLR in the rPVE+S4 group (48 vs 38% and 155 vs 112ml, p=0.01 and 0.02). In this large multicenter cohort study, additional embolization of S4 did demonstrate superior growth of the FLR compared to standard right PVE.

Proteomic characterization of biological features in the small for size future rat liver remnant

Small for size liver syndrome (SFSLS) may occur after extended partial hepatectomy (PH); characterized by insufficient function of the future liver remnant (FLR); biochemically demonstrated by low proconvertin-prothrombin-ratio (PP) and high bilirubin (BR). The aim of this ongoing study is to characterize differences in protein expression between different size of FLRs and to identify proteins specific for the regenerative process of minimal size FLR (MSFLR). 104 male Wistar rats subjected to 30%, 70%, or 90% PH (MSFLR in rats); SHAM or no operation. Blood and liver tissue harvested at post-operative day (POD)1, 3, and 5 (n=8 per group). Main parameters assessed: Proteomic expression by 2D-PAGE and liquid-chromatography mass-spectrometry, liver regeneration rate (RR) by change in liver weight, and serum PP and BR. 149 protein-spots were significantly different expressed between groups (FDR< 0.05, fold-change>2). By hierarchical cluster analysis 3 separate clusters formed: PH(90) POD1, POD3, POD5. Identification of the protein spots revealed 57 proteins, all specific for PH(90)-groups (up-/down-regulated compared to the other groups). RR increased significantly with size of PH. Significantly, PP was critically reduced in PH(90) at POD1 and BR elevated; both normalized at POD5. Most pronounced changes in proteomic expression after PH were found in the PH(90)-group; initially mimicking SFSLS by low PP and high BR at POD1, later recuperating liver function and growth. 57 proteins specific for PH(90)-groups were identified pending further ongoing analyses. Identification of biological factors of liver regeneration in MSFLR is important in attempt to improve outcome after extended PH and potential SFSLS.

Experimental evaluation of liver regeneration patterns and liver function following ALPPS.

BackgroundThe underlying mechanism of liver regeneration after Associating Liver Partition and Portal vein ligation (PVL) for Staged hepatectomy (ALPPS) is still unclear. The aim of this study was to evaluate the relationship between future liver remnant (FLR) volume, liver regeneration characteristics and restoration of function in an experimental model of ALPPS.MethodsAn ALPPS model in rats was developed with selective PVL, parenchymal transection and partial hepatectomy (step 1), followed by resection of the liver (step 2). Three different ALPPS groups with FLR sizes of 30, 20 and 10 per cent of total liver volume were compared with sham‐operated controls and animals undergoing resection of left lateral lobe and 90 per cent PVL with respect to morbidity, mortality, liver regeneration and function.ResultsThree of 15 animals that had ALPPS with 10 per cent FLR (ALPPS10) died after step 1. Ascites developed in two of five rats that had ALPPS with 20 per cent FLR and in three of four animals in the ALPPS10 group after step 2. Although the relative increments in FLR size and growth rates were highest in the ALPPS groups, small FLR size was associated with a sustained increase in levels of serum aminotransferases and bilirubin, a lower albumin concentration, severe sinusoidal injury, increased expression of proliferation markers and increased activation of hepatic progenitor cells after step 2.ConclusionThere is discordance between FLR volume increase and functional restoration after the ALPPS procedure.

Prediction of Mortality After ALPPS Stage-1: An Analysis of 320 Patients From the International ALPPS Registry.

The aim of this study was to identify predictors of 90-day mortality after Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS), available after stage-1, either to omit or delay stage-2. ALPPS is a two-stage hepatectomy for patients with extensive liver tumors with predicted small liver remnants, which has been criticized for its high mortality rate. Risk factors for mortality are unknown. Patients in the International Registry undergoing ALPPS from April 2011 to July 2014 were analyzed. Primary outcome was 90-day mortality. Liver function after stage-1 was assessed using the criteria of the International Study Group for Liver Surgery (ISGLS) after stage-1 among others. A multivariable model was used to identify independent predictors of 90-day mortality. Three hundred twenty patients registered by 55 centers worldwide were evaluated. Overall 90-day mortality was 8.8% (28/320). The predominant cause for 90-day mortality was postoperative liver failure in 75% of patients. Fourteen percent of patients developed liver failure according to ISGLS criteria already after stage-1 ALPPS. Those and patients with a model of end-stage liver disease (MELD) score more than 10 before stage-2 were at significantly higher risk for 90-day mortality after stage-2 with an odds ratio (OR) 3.9 [confidence interval (CI) 1.4-10.9, P = 0.01] and OR 4.9 (CI 1.9-12.7, P = 0.006), respectively. Other factors, such as size of future liver remnant (FLR) before stage-2 and time between stages, were not predictive. This analysis of the largest cohort of ALPPS patients so far identifies those patients in whom stage-2 ALPPS surgery should be delayed or even denied. These findings may help to make ALPPS safer.

Is the liver kinetic growth rate in ALPPS unprecedented when compared with PVE and living donor liver transplant? A multicentre analysis

BackgroundThe clinical perspective on hepatic growth is limited. The goal of the present study was to compare hepatic hypertrophy and the kinetic growth rate(KGR) in patients after the ALPPS (Associating Liver Partition with Portal Vein Ligation for Staged Hepatectomy) procedure, portal vein embolization (PVE) and living donor liver transplantation. MethodsVolumetry and KGR of the future liver remnant (FLR) were compared from (15) patients undergoing ALPPS, (53) patients undergoing PVE, (90) recipients of living donor liver grafts and (93) donors of living donor liver grafts. ResultsThe degree of hypertrophy was significantly greater after ALPPS (84.3 ± 7.8%) than after PVE (36.0 ± 27.2%) (P < 0.001). The KGR was also significantly greater for ALPPS [32.7 ± 13.6 cubic centimetres (cc)/day] (10.8 ± 4.5%/day) compared with PVE (4.4 ± 3.2 cc/day) (0.98 ± 0.75%/day) (P < 0.001). The FLR of living donor donors had the greatest degree of hypertrophy (107.5 ± 39.2%) and was greater than after ALPPS (P = 0.02), PVE (P < 0.001) and in living donor‐recipient grafts (P < 0.001). KGR (cc/day) was greater in FLR of living donor donors compared with both ALPPS (P < 0.001) and PVE (P < 0.001). The KGR in patients undergoing ALPPS and living donor liver transplantation had a linear relationship with the size of FLR. ConclusionFLR hypertrophy and KGR were greater after ALPPS than PVE. However, the degree of hypertrophy after ALPPS is not unprecedented, as KGR in the FLR from living donor donors is equal to or greater than after ALPPS. The KGR of the FLR in patients after ALPPS and living donor donors correlates directly with the size of the FLR.

Percutaneous transhepatic portal vein embolization: effectiveness of absolute ethanol infusion with balloon catheter in a pig model

To evaluate the effectiveness of portal vein embolization (PVE) with absolute ethanol using multidetector-row computed tomography (CT) angiography in a pig model. Percutaneous transhepatic PVE with 10 ml absolute ethanol was performed in liver segments (n = 5) or subsegments (n = 5) in 10 pigs. CT images and volumetric data were qualitatively and quantitatively assessed to determine future liver remnant (FLR) hypertrophy and to correlate with histopathologic changes 2-6 weeks after PVE. Effectiveness evaluation was based on changes in absolute FLR size and ratio of FLR to total estimated liver volume (TELV). Occlusion of the embolized vessel was achieved immediately after injecting absolute ethanol within a range of 0.25-0.33 ml/kg. The TELV prior to PVE was 660.49 +/- 103.66 cm3 (range 527.22 to 833.70 cm3) and after PVE 769.51 +/- 29.36 cm3 (range 685.95 to 887.34 cm3). The mean FLR/TELV ratio increase after PVE was 14.2%. No statistically significant difference was found in the increase of TELV between segmental or subsegmental PVE. On microscopic observation, atrophy of the embolized liver was noted in all animals and was seen distinctly at 3 weeks after PVE in 2 animals. Both regenerative response and histopathologic changes of the liver were seen after PVE with absolute ethanol with a mean FLR/TELV ratio of 14.2%.

Portal vein embolization with polyvinyl alcohol particles and coils in preparation for major liver resection for hepatobiliary malignancy: safety and effectiveness--study in 26 patients.

To evaluate whether preoperative portal vein embolization (PVE) with polyvinyl alcohol (PVA) particles and coils is safe and effective for inducing lobar hypertrophy in patients with hepatobiliary malignancy. PVE was performed in 26 patients. All patients had malignancy: metastases (n = 11), cholangiocarcinoma (n = 9), hepatocellular carcinoma (n = 5), and gallbladder carcinoma (n = 1). One patient had underlying liver disease caused by hepatitis. PVE was performed if the future liver remnant (FLR) was estimated to be less than 25% of the total liver volume. PVE was performed with a percutaneous transhepatic approach (right, 25 patients; left, one patient). PVA particles and coils were used to occlude the right portal system and veins supplying segment IV to promote FLR hypertrophy (segments I-III +/- IV). FLR hypertrophy was assessed with comparison of computed tomographic scans obtained before and 2-4 weeks after PVE. Effectiveness evaluation was based on changes in absolute FLR size and ratio of FLR to total estimated liver volume (TELV). Safety of PVE and hepatic resection was determined with postprocedure complication rate and median hospital stay. Sixteen patients underwent hepatic resection (right trisegmentectomy [n = 13], right lobectomy [n = 3]) without mortality. Ten patients did not undergo resection (complete remission after medical therapy [n = 1], lack of regeneration [n = 2], extrahepatic disease undetected prior to PVE [n = 7]). Six patients had biliary obstruction; five were treated percutaneously before PVE. No patient developed postembolization syndrome or signs of fulminant hepatic insufficiency after PVE or resection. Two patients had complications after PVE that did not preclude successful resection. Median hospital stays were 1 day (PVE) and 7 days (liver resection). Mean absolute FLR increased from 325.0 to 458.6 cm3 (increase, 41.1%). Mean TELV was 1,784.8 cm3. FLR/TELV ratio increase was 8%. Preoperative PVE with PVA particles and coils is safe and effective for inducing lobar hypertrophy in patients with advanced hepatobiliary malignancy.