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2021 ◽  
Author(s):  
Cheng-Cheng Shi ◽  
Yang Bai ◽  
Xin Yan ◽  
Nuo Cheng ◽  
Wen-Zhi Guo ◽  
...  

The regulation mechanism of small-for-size syndrome remains unclear. Thus, we aimed to analyze the molecular profiles following extended hepatectomy and identify the therapeutic target. Major hepatectomy and extended hepatectomy were performed in the rat model, and the remnant livers were obtained dynamically for the high-throughput transcriptome analysis to identify the differentially expressed genes (DEGs). The general framework for weighted gene co-expression network analysis (WGCNA) was employed to explore the expression patterns of DEGs. As result, WGCNA identified 10 distinct gene co-expression modules according to the correlation between module eigengene and different postoperative time-points. The magenta module and the lightcyan module were found positively correlated with not extended hepatectomy but major hepatectomy. In the lightcyan module, peroxisome proliferator-activated receptor- (PPAR) was selected and verified the down-regulation in the remnant liver following extended hepatectomy in rats and humans. Besides, administration of PPAR agonist attenuated hepatic inflammation injury while PPAR antagonist increased liver inflammation injury after extended hepatectomy in rats, marked by the significantly changed aminotransferases, tumor necrosis factor- and interleukin-6 levels in the plasm, and histological Suzuki criteria. Consequently, DEGs and their molecular profiles after extended hepatectomy were identified, and PPAR might be a potential therapy target for small-for-size syndrome.


Author(s):  
Michail Papamichail ◽  
Michail Pizanias ◽  
Nigel D Heaton ◽  
Papamichail M ◽  
Pizanias M ◽  
...  
Keyword(s):  

2021 ◽  
Author(s):  
Alexandre de Abreu Ribeiro ◽  
Christina Maeda Takiya ◽  
Vera Nunes Pannain ◽  
Mauricio Andrade Perez ◽  
Joaquim Ribeiro Filho

Abstract The increase of liver surgical indications, the expansion of the margins in hepatic resections and the lack of organ donors led to the use of more split livers from cadaver and living donors and smaller liver remnants in post-operatory patients. The use of increasingly smaller grafts associated with hepatic resections broadened the spectrum for observation of small-for size syndrome, caused by significant inflammation and early hepatic fibrosis. The small-for-size syndrome is manifested clinically by prolonged cholestasis, refractory ascites and progressive hepatic dysfunction (encephalopathy and coagulopathy). In the search for mechanisms to reduce liver damage, preconditioning is presented as a possibility of protecting the low weight remnant in experimental works. Objective: Study the hepatic tissue measuring the impact of portal preconditioning in small hepatic remnant in Wistar rats Methods: Rats weighing approximately 250g were divided in 4 groups with 7 members each. Group 1, Control group requiring only collection of the material, blood laboratory analysis and liver biopsy for pathology and immunohistochemistry; Group 2, Sham, were operated with simple laparotomy, 48 hours later they were subjected to another surgery with sample collection to do blood laboratory analysis and liver biopsy for pathology and immunohistochemistry. Group 3, hepatectomy with preconditioning. In this group was made the preconditioning procedure before the resection of 70% of the liver, 48 hours later they underwent another surgery for sample collection to do blood laboratory analysis and liver biopsy for pathology and immunohistochemistry. Group 4, hepatectomy without preconditioning. In this group the members were operated with resection of 70% of the liver, 48 hours later were reoperated with sample collection to do blood laboratory analysis and liver biopsy for pathology and immunohistochemistry. We studied and compared the impacts in morphology, laboratory, histology, immunohistochemistry.Results: There was no intraoperative mortality in the model used, there was no statistically significant difference in histological and laboratory parameters between the groups with and without preconditioning, there was an increase in the expression of PCNA with statistical significance in the hepatic remnant of the group submitted to preconditioning. Conclusion: Liver preconditioning can provide an increase in cell proliferation in small volume liver remnant.


2021 ◽  
Author(s):  
Samuele Iesari ◽  
Isabelle Leclercq ◽  
Nicolas Joudiou ◽  
Mina Komuta ◽  
Aurélie Daumerie ◽  
...  

Background: Small-for-size syndrome looms over patients needing liver resection or living-donor transplantation. Hypoxia has been shown to be crucial for the successful outcome of liver resection in the very early postoperative phase. While poorly acceptable as such in real-world clinical practice, hypoxia responses can still be simulated by pharmacologically raising levels of its transducers, the hypoxia-inducible factors (HIF). We aimed to assess the potential role of a selective inhibitor of HIF degradation in 70% hepatectomy (70%Hx). Methods: In a pilot study, we tested the required dose of roxadustat to stabilize liver HIF1α. We then performed 70%Hx in 8-week-old male Lewis rats and administered 25 mg/kg of roxadustat (RXD25) at the end of the procedure. Regeneration was assessed: ki67 and EdU immunofluorescent labeling, and histological parameters. We also assessed liver function via a blood panel and functional gadoxetate-enhanced magnetic resonance imaging, up to 47 hours after the procedure. Metabolic results were analyzed by means of RNA sequencing. Results: Roxadustat effectively increased early HIF1α transactivity. Liver function did not appear to be improved nor liver regeneration to be accelerated by the experimental compound. However, treated livers showed a mitigation in hepatocellular steatosis and ballooning, known markers of cellular stress after liver resection. RNA sequencing confirmed that roxadustat unexpectedly increases lipid breakdown and cellular respiration. Conclusions: Selective HIF stabilization did not result in an enhanced liver function after standard liver resection, but it induced interesting metabolic changes that are worth studying for their possible role in extended liver resections and fatty liver diseases.


2021 ◽  
Vol 22 (15) ◽  
pp. 8053
Author(s):  
Maxime De Rudder ◽  
Alexandra Dili ◽  
Peter Stärkel ◽  
Isabelle A. Leclercq

Liver sinusoids are lined by liver sinusoidal endothelial cells (LSEC), which represent approximately 15 to 20% of the liver cells, but only 3% of the total liver volume. LSEC have unique functions, such as fluid filtration, blood vessel tone modulation, blood clotting, inflammatory cell recruitment, and metabolite and hormone trafficking. Different subtypes of liver endothelial cells are also known to control liver zonation and hepatocyte function. Here, we have reviewed the origin of LSEC, the different subtypes identified in the liver, as well as their renewal during homeostasis. The liver has the exceptional ability to regenerate from small remnants. The past decades have seen increasing awareness in the role of non-parenchymal cells in liver regeneration despite not being the most represented population. While a lot of knowledge has emerged, clarification is needed regarding the role of LSEC in sensing shear stress and on their participation in the inductive phase of regeneration by priming the hepatocytes and delivering mitogenic factors. It is also unclear if bone marrow-derived LSEC participate in the proliferative phase of liver regeneration. Similarly, data are scarce as to LSEC having a role in the termination phase of the regeneration process. Here, we review what is known about the interaction between LSEC and other liver cells during the different phases of liver regeneration. We next explain extended hepatectomy and small liver transplantation, which lead to “small for size syndrome” (SFSS), a lethal liver failure. SFSS is linked to endothelial denudation, necrosis, and lobular disturbance. Using the knowledge learned from partial hepatectomy studies on LSEC, we expose several techniques that are, or could be, used to avoid the “small for size syndrome” after extended hepatectomy or small liver transplantation.


2021 ◽  
Vol 8 ◽  
Author(s):  
Xishu Wang ◽  
Yongrong Lei ◽  
Hongbo Huan ◽  
Shu Chen ◽  
Kuansheng Ma ◽  
...  

Aim: To compare the short- and long-term treatment outcomes of bisegmentectomy 7–8 vs. right hepatectomy for patients with hepatocellular carcinoma and cirrhosis.Methods: Thirty six cirrhotic HCC patients with infiltration of right hepatic vein in segments 7–8 underwent bisegmentectomy 7–8 for small-for-size remanant liver under right hemi-hepatectomy. Its outcome was compared with a case-matched control group of cirrhotic HCC patients who underwent right hemi-hepatectomy during the study period.Results: The study group consisted of 36 patients and the control group 36 patients selected from 1,526 patients matched with age, tumor size, tumor location, and Pugh-Child staging. There were no significant differences between the two groups in operative parameters and in perioperative main complications which included hemorrhage, bile leakage, ascites, pleural effusion, and liver failure. The overall morbidity rate and morbidity rate classified according to Clavien's classification were similar. There was no in-hospital mortality or 90 day post-operative mortality. The mean follow-up was 30 and 32 months for the study group and control group, respectively. The disease free survival rate (DFS) for the study group was just significantly better than the control group. The median DFS was 24 months for the study group and 8 months for the control group (P = 0.049). Meanwhile, the median cumulative overall survival was 35 months for the study group and 27 months for the control group (P = 0.494).Conclusion: Bisegmentectomy 7–8 was safe and feasible for selected cirrhosis patients, and did not increase the perioperative risk and inferior long-term overall survival outcomes. It extended the indications for liver resection in patients with borderline volumes of future liver remnant for HCC cirrhotic liver.


2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Xiao Bing Liu ◽  
Hui Liu ◽  
Jiang Liu ◽  
Allen Ka Loon Cheung ◽  
Ming Zhu Zheng ◽  
...  

BMC Surgery ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Pål-Dag Line ◽  
Silvio Nadalin ◽  
Deniz Balci

AbstractA case report of two patients who underwent auxiliary liver transplantation and two staged hepatectomy was recently published in BMC Surgery. The surgical technique utilised is described as novel but has been published previously also in the setting of chronic liver disease. A new name for this surgical approach therefore seems redundant. The importance of careful hemodynamic monitoring of pressure and flow in the portal vein and artery of the auxiliary graft as well as optimizing venous outflow is paramount to ensure graft regeneration and avoid small for size syndrome. The relevant surgical considerations to ensure optimal safety has also been reported in previous literature. This brief letter to the editor of BMC Surgery gives an overview that put the article content in context with published literature on this transplant surgical technique.


BMC Surgery ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Stefan M. Brunner ◽  
Frank W. Brennfleck ◽  
Henrik Junger ◽  
Jirka Grosse ◽  
Birgit Knoppke ◽  
...  

Abstract Background Risks for living-liver donors are lower in case of a left liver donation, however, due to lower graft volume, the risk for small-for-size situations in the recipients increases. This study aims to prevent small-for-size situations in recipients using an auxiliary two-staged partial resection liver transplantation (LTX) of living-donated left liver lobes. Case presentation Two patients received a two-stage auxiliary LTX using living-donated left liver lobes after left lateral liver resection. The native extended right liver was removed in a second operation after sufficient hypertrophy of the left liver graft had occurred. Neither donor developed postoperative complications. In both recipients, the graft volume increased by an average of 105% (329 ml to 641 ml), from a graft-to-body-weight ratio of 0.54 to 1.08 within 11 days after LTX, so that the remnant native right liver could be removed. No recipient developed small-for-size syndrome; graft function and overall condition is good in both recipients after a follow-up time of 25 months. Conclusions Auxiliary two-staged partial resection LTX using living-donor left lobes is technically feasible and can prevent small-for-size situation. This new technique can expand the potential living-donor pool and contributes to increase donor safety.


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