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Background: The bile salt-activated transcription factor farnesoid X receptor (FXR) is a key mediator of proliferative bile salt signalling, which is assumed to play a role in the early phase of compensatory liver growth. The aim of this study was to evaluate the effect of a potent FXR agonist (obeticholic acid, OCA) on liver growth following portal vein embolization (PVE)., Methods: Rabbits were allocated to receive daily oral gavage with OCA (10 mg/kg) or vehicle (control group) starting 7 days before PVE (n = 18 per group), and continued until 7 days after PVE. PVE of the cranial liver lobes was performed using polyvinyl alcohol particles and coils on day 0. Caudal liver volume (CLV) was analysed by CT volumetry on days -7, -1, +3 and +7. Liver function was determined by measuring mebrofenin uptake using hepatobiliary scintigraphy. Additional parameters analysed were plasma aminotransferase levels, and histological scoring of haematoxylin and eosin- and Ki-67-stained liver sections., Results: Three days after PVE of the cranial lobes, the increase in CLV was 2·2-fold greater in the OCA group than in controls (mean(s.d.) 56·1(20·3) versus 26·1(15·4) per cent respectively; P < 0·001). This increase remained greater 7 days after PVE (+1·5-fold; P = 0·020). The increase in caudal liver function at day +3 was greater in OCA-treated animals (+1·2-fold; P = 0·017). The number of Ki-67-positive hepatocytes was 1·6-fold higher in OCA-treated animals 3 days after PVE (P = 0·045). Plasma aminotransferase levels and histology did not differ significantly between groups., Conclusion: OCA accelerated liver regeneration after PVE in a rabbit model. OCA treatment might increase the efficacy of PVE and, thereby, resectability. Surgical relevance Liver failure is the most feared complication after liver surgery, with no effective treatment options. Liver regeneration is essential to avoid liver failure, and recently bile acid signalling was implicated in the initiation of liver regeneration through the nuclear bile acid receptor farnesoid X receptor (FXR). In this study, the potent FXR agonist obeticholic acid accelerated liver regeneration following portal vein embolization in a rabbit model, in terms of liver volume, liver function and proliferation. Obeticholic acid treatment could enhance the efficacy of portal vein embolization, thereby increasing resectability, and could reduce the interval to surgery. In addition, obeticholic acid might have a place in the prevention of liver failure after liver surgery., (© 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Introduction: Irreversible electroporation (IRE) is a novel ablation technique in the treatment of unresectable cancer. The non-thermal mechanism is thought to cause mostly apoptosis compared to necrosis in thermal techniques. Both in experimental and clinical studies, a waiting time between ablation and tissue or imaging analysis to allow for cell death through apoptosis, is often reported. However, the dynamics of the IRE effect over time remain unknown. Therefore, this study aims to summarize these effects in relation to the time between treatment and evaluation., Methods: A systematic search was performed in Pubmed, Embase and the Cochrane Library for original articles using IRE on pancreas, liver or surrounding structures in animal or human studies. Data on pathology and time between IRE and evaluation were extracted., Results: Of 2602 screened studies, 36 could be included, regarding IRE in liver (n = 24), pancreas (n = 4), blood vessels (n = 4) and nerves (n = 4) in over 440 animals (pig, rat, goat and rabbit). No eligible human studies were found. In liver and pancreas, the first signs of apoptosis and haemorrhage were observed 1-2 hours after treatment, and remained visible until 24 hours in liver and 7 days in pancreas after which the damaged tissue was replaced by fibrosis. In solitary blood vessels, the tunica media, intima and lumen remained unchanged for 24 hours. After 7 days, inflammation, fibrosis and loss of smooth muscle cells were demonstrated, which persisted until 35 days. In nerves, the median time until demonstrable histological changes was 7 days., Conclusions: Tissue damage after IRE is a dynamic process with remarkable time differences between tissues in animals. Whereas pancreas and liver showed the first damages after 1-2 hours, this took 24 hours in blood vessels and 7 days in nerves., Competing Interests: K. P. van Lienden and M. R. Meijerink are paid consultants for Angiodynamics. L. G. Vroomen received an unrestricted grant from AngioDynamics for clinical studies on IRE. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Portal vein embolization (PVE) is used to increase future remnant liver size in patients requiring major hepatic resection. PVE using permanent embolization, however, predisposes to complications and excludes the use of PVE in living donor liver transplantation. In the present study, an absorbable embolization material containing fibrin glue and different concentrations of the fibrinolysis inhibitor aprotinin was used in an experimental animal model., Methods: PVE of the cranial liver lobes was performed in 30 New Zealand White rabbits, which were divided into five groups, fibrin glue + 1000, 700, 500, 300 or 150 kunits/ml aprotinin, and were compared with a previous series of permanent embolization using the same experimental set-up. Caudal liver lobe hypertrophy was determined by CT volumetry, and portal recanalization was identified on contrast-enhanced CT images. Animals were killed after 7 or 42 days, and the results were compared with those of permanent embolization., Results: PVE using fibrin glue with aprotinin as embolic material was effective, with 500 kunits/ml providing the optimal hypertrophic response. Lower concentrations of aprotinin (150 and 300 kunits/ml) led to reduced hypertrophy owing to early recanalization of the embolized segments. The regeneration rate over the first 3 days was higher in the group with 500 kunits/ml aprotinin than in the groups with 300 or 150 kunits/ml or permanent embolization. In the 500-kunits/ml group, four of five animals showed recanalization 42 days after embolization, with minimal histological changes in the cranial lobes following recanalization., Conclusion: Fibrin glue combined with 500 kunits/ml aprotinin resulted in reversible PVE in 80 per cent of animals, with a hypertrophy response comparable to that achieved with permanent embolization material. Surgical relevance Portal vein embolization (PVE) is used to increase future remnant liver volume in patients scheduled for major liver resection who have insufficient future remnant liver size to perform a safe resection. The current standard is PVE with permanent embolization materials, which renders patients found to have unresectable disease prone to complications owing to the permanently deportalized liver segments. Absorbable embolization might prevent the PVE-associated morbidity and lower the threshold for its application. In this study, PVE using fibrin glue and aprotinin resulted in an adequate hypertrophy response with 80 per cent recanalization after 42 days. Considering the minor histological changes following recanalization of embolized segments and potentially preserved function, reversible PVE might also be applied in living donor liver transplantation., (© 2016 BJS Society Ltd Published by John Wiley & Sons Ltd.)

In 3 children, 2 boys aged 13 years and an 8-year-old girl, blunt trauma to the liver was diagnosed after a fall. The first patient underwent drainage of abdominal fluid collection on multiple occasions and a stent was introduced in the biliary duct to ensure normal bile flow; the second patient was treated by arterial catheter embolisation of a segmental branch of the right hepatic artery; in the third patient, acute laparotomy was performed in view ofhaemodynamic instability and a large hepatic rupture was treated by packing. All patients recovered successfully. In the paediatric population, blunt trauma to the liver requires a multidisciplinary approach. For haemodynamically stable children, a conservative course can be taken. Arterial embolisation is the treatment of choice if there is a persistent need for volume resuscitation or blood transfusion. In case of massive haemorrhagic shock, the child should undergo laparotomy, and if the bleeding cannot be stopped, the liver should be packed according to damage-control principles.

This systematic review was conducted to determine factors that are associated with the degree of hypertrophy of the future liver remnant following portal vein embolization. An extensive search on September 15, 2020, and subsequent literature screening resulted in the inclusion of forty-eight articles with 3368 patients in qualitative analysis, of which 18 studies were included in quantitative synthesis. Meta-analyses based on a limited number of studies showed an increase in hypertrophy response when additional embolization of segment 4 was performed (pooled difference of medians = − 3.47, 95% CI − 5.51 to − 1.43) and the use of N-butyl cyanoacrylate for portal vein embolization induced more hypertrophy than polyvinyl alcohol (pooled standardized mean difference (SMD) = 0.60, 95% CI 0.30 to 0.91). There was no indication of a difference in degree of hypertrophy between patients who received neo-adjuvant chemotherapy and those who did not receive pre-procedural systemic therapy (pooled SMD = − 0.37, 95% CI − 1.35 to 0.61), or between male and female patients (pooled SMD = 0.19, 95% CI − 0.12 to 0.50). The study was registered in the International Prospective Register of Systematic Reviews on April 28, 2020 (CRD42020175708). [ABSTRACT FROM AUTHOR]

Background: Preoperative portal vein embolization (PVE) is performed in patients with insufficient future remnant liver (FRL) to allow safe resection. Although many studies have demonstrated an increase in FRL volume after PVE, little is known about the increase in FRL function. This study evaluated the increase in FRL function after PVE using 99mTc-labelled mebrofenin hepatobiliary scintigraphy (HBS) with single photon emission computed tomography (SPECT) and compared this with the increase in FRL volume. Methods: In 24 patients, computed tomography volumetry and 99mTc-labelled mebrofenin HBS with SPECT were performed before and 3-4 weeks after PVE to measure FRL volume, standardized FRL and FRL function. A hypothetical model was used to assess safe resectability after PVE. The limit for safe resection for FRL function was set at an uptake of 2.69 per cent per min per m². For FRL volume and standardized FRL, 25 or 40 per cent of total liver volume was used, depending on the presence of underlying liver disease. Results: After PVE, FRL function increased significantly more than FRL volume. The correlation between the increase in FRL volume and FRL function was poor. Using the hypothetical model, seven patients did not achieve a sufficient increase in FRL function to allow safe resection 3-4 weeks after PVE, compared with 12 and nine patients based on FRL volume and standardized FRL respectively. Conclusion: The increase in FRL function after PVE is more pronounced than the increase in FRL volume, suggesting that the necessary waiting time until resection may be shorter than indicated by volumetric parameters. [ABSTRACT FROM AUTHOR]