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Affiliation(s)
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1
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Boubaddi M, Marichez A, Adam JP, Lapuyade B, Debordeaux F, Tlili G, Chiche L, Laurent C. Comprehensive Review of Future Liver Remnant (FLR) Assessment and Hypertrophy Techniques Before Major Hepatectomy: How to Assess and Manage the FLR. Ann Surg Oncol 2024; 31:9205-9220. [PMID: 39230854 DOI: 10.1245/s10434-024-16108-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Accepted: 08/16/2024] [Indexed: 09/05/2024]
Abstract
BACKGROUND The regenerative capacities of the liver and improvements in surgical techniques have expanded the possibilities of resectability. Liver resection is often the only curative treatment for primary and secondary malignancies, despite the risk of post-hepatectomy liver failure (PHLF). This serious complication (with a 50% mortality rate) can be avoided by better assessment of liver volume and function of the future liver remnant (FLR). OBJECTIVE The aim of this review was to understand and assess clinical, biological, and imaging predictors of PHLF risk, as well as the various hypertrophy techniques, to achieve an adequate FLR before hepatectomy. METHOD We reviewed the state of the art in liver regeneration and FLR hypertrophy techniques. RESULTS The use of new biological scores (such as the aspartate aminotransferase/platelet ratio index + albumin-bilirubin [APRI+ALBI] score), concurrent utilization of 99mTc-mebrofenin scintigraphy (HBS), or dynamic hepatocyte contrast-enhanced MRI (DHCE-MRI) for liver volumetry helps predict the risk of PHLF. Besides portal vein embolization, there are other FLR optimization techniques that have their indications in case of risk of failure (e.g., associating liver partition and portal vein ligation for staged hepatectomy, liver venous deprivation) or in specific situations (transarterial radioembolization). CONCLUSION There is a need to standardize volumetry and function measurement techniques, as well as FLR hypertrophy techniques, to limit the risk of PHLF.
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Affiliation(s)
- Mehdi Boubaddi
- Hepatobiliary and Pancreatic Surgery Department, Bordeaux University Hospital Center, Bordeaux, France.
- Bordeaux Institute of Oncology, BRIC U1312, INSERM, Bordeaux University, Bordeaux, France.
| | - Arthur Marichez
- Hepatobiliary and Pancreatic Surgery Department, Bordeaux University Hospital Center, Bordeaux, France
- Bordeaux Institute of Oncology, BRIC U1312, INSERM, Bordeaux University, Bordeaux, France
| | - Jean-Philippe Adam
- Hepatobiliary and Pancreatic Surgery Department, Bordeaux University Hospital Center, Bordeaux, France
| | - Bruno Lapuyade
- Radiology Department, Bordeaux University Hospital Center, Bordeaux, France
| | - Frederic Debordeaux
- Nuclear Medicine Department, Bordeaux University Hospital Center, Bordeaux, France
| | - Ghoufrane Tlili
- Nuclear Medicine Department, Bordeaux University Hospital Center, Bordeaux, France
| | - Laurence Chiche
- Hepatobiliary and Pancreatic Surgery Department, Bordeaux University Hospital Center, Bordeaux, France
| | - Christophe Laurent
- Hepatobiliary and Pancreatic Surgery Department, Bordeaux University Hospital Center, Bordeaux, France
- Bordeaux Institute of Oncology, BRIC U1312, INSERM, Bordeaux University, Bordeaux, France
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2
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Pandey K, Dash D, Koiri RK. Liver lobes and cirrhosis: Diagnostic insights from lobar ratios. GASTROENTEROLOGY & ENDOSCOPY 2024. [DOI: 10.1016/j.gande.2024.10.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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3
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Liu Q, Wang S, Fu J, Chen Y, Xu J, Wei W, Song H, Zhao X, Wang H. Liver regeneration after injury: Mechanisms, cellular interactions and therapeutic innovations. Clin Transl Med 2024; 14:e1812. [PMID: 39152680 PMCID: PMC11329751 DOI: 10.1002/ctm2.1812] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2024] [Revised: 07/27/2024] [Accepted: 08/03/2024] [Indexed: 08/19/2024] Open
Abstract
The liver possesses a distinctive capacity for regeneration within the human body. Under normal circumstances, liver cells replicate themselves to maintain liver function. Compensatory replication of healthy hepatocytes is sufficient for the regeneration after acute liver injuries. In the late stage of chronic liver damage, a large number of hepatocytes die and hepatocyte replication is blocked. Liver regeneration has more complex mechanisms, such as the transdifferentiation between cell types or hepatic progenitor cells mediated. Dysregulation of liver regeneration causes severe chronic liver disease. Gaining a more comprehensive understanding of liver regeneration mechanisms would facilitate the advancement of efficient therapeutic approaches. This review provides an overview of the signalling pathways linked to different aspects of liver regeneration in various liver diseases. Moreover, new knowledge on cellular interactions during the regenerative process is also presented. Finally, this paper explores the potential applications of new technologies, such as nanotechnology, stem cell transplantation and organoids, in liver regeneration after injury, offering fresh perspectives on treating liver disease.
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Affiliation(s)
- Qi Liu
- Translational Medicine CentreThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina
- Department of Hepatobiliary and Pancreatic SurgeryThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina
| | - Senyan Wang
- Translational Medicine CentreThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina
- Department of Hepatobiliary and Pancreatic SurgeryThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina
| | - Jing Fu
- International Cooperation Laboratory on Signal TransductionNational Center for Liver CancerMinistry of Education Key Laboratory on Signaling Regulation and Targeting Therapy of Liver CancerShanghai Key Laboratory of Hepato‐biliary Tumor BiologyEastern Hepatobiliary Surgery Hospital, Second Military Medical University/NAVAL Medical UniversityShanghaiChina
| | - Yao Chen
- International Cooperation Laboratory on Signal TransductionNational Center for Liver CancerMinistry of Education Key Laboratory on Signaling Regulation and Targeting Therapy of Liver CancerShanghai Key Laboratory of Hepato‐biliary Tumor BiologyEastern Hepatobiliary Surgery Hospital, Second Military Medical University/NAVAL Medical UniversityShanghaiChina
| | - Jing Xu
- Translational Medicine CentreThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina
| | - Wenjuan Wei
- Translational Medicine CentreThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina
| | - Hao Song
- Translational Medicine CentreThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina
| | - Xiaofang Zhao
- Translational Medicine CentreThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina
| | - Hongyang Wang
- International Cooperation Laboratory on Signal TransductionNational Center for Liver CancerMinistry of Education Key Laboratory on Signaling Regulation and Targeting Therapy of Liver CancerShanghai Key Laboratory of Hepato‐biliary Tumor BiologyEastern Hepatobiliary Surgery Hospital, Second Military Medical University/NAVAL Medical UniversityShanghaiChina
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4
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Ferraina F, Fogliati A, Scotti MA, Romano F, Garancini M, Ciulli C. Lobar and Segmental Atrophy of the Liver: Differential Diagnoses and Treatments. LIVERS 2024; 4:320-332. [DOI: 10.3390/livers4030023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/22/2024] Open
Abstract
Segmental or lobar liver atrophy is a common but not well-understood clinical condition. Hepatic atrophy can be classified into hepatic atrophy secondary to other pathologies and primary segmental hepatic atrophy, which is a benign intrahepatic lesion (pseudotumor) not associated with any other pathology. The pathophysiological mechanisms underlying atrophy can be divided into three main situations: obstruction of biliary outflow, obstruction of the systemic venous outflow, and obstruction of incoming portal venous flow. For what may concern secondary hepatic atrophy, there are many pathologies that could underlie this condition, ranging from benign to intrahepatic malignancies, with particular reference to particularly hepatocellular carcinoma and biliary duct carcinoma. An accurate and prompt differential diagnosis between the various forms and causes of atrophy is important for early identification and adequate treatment of underlying pathologies. A comprehensive review of the literature on the etiology and the radiological and histological characteristics of different types of hepatic atrophy is currently unavailable. Therefore, the aim of this review is to summarize the primary and secondary causes of segmental or lobar liver atrophy (excluding forms involving the entire liver parenchyma) and to provide practical tools for clinical and radiological differential diagnosis.
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Affiliation(s)
- Federica Ferraina
- School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy
| | - Alessandro Fogliati
- School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy
- HPB Surgery Unit, Department of General Surgery, IRCCS San Gerardo dei Tintori Foundation, 20900 Monza, Italy
| | - Mauro Alessandro Scotti
- HPB Surgery Unit, Department of General Surgery, IRCCS San Gerardo dei Tintori Foundation, 20900 Monza, Italy
| | - Fabrizio Romano
- School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy
- HPB Surgery Unit, Department of General Surgery, IRCCS San Gerardo dei Tintori Foundation, 20900 Monza, Italy
| | - Mattia Garancini
- School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy
- HPB Surgery Unit, Department of General Surgery, IRCCS San Gerardo dei Tintori Foundation, 20900 Monza, Italy
| | - Cristina Ciulli
- HPB Surgery Unit, Department of General Surgery, IRCCS San Gerardo dei Tintori Foundation, 20900 Monza, Italy
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5
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Chan SM, Cornman-Homonoff J, Lucatelli P, Madoff DC. Image-guided percutaneous strategies to improve the resectability of HCC: Portal vein embolization, liver venous deprivation, or radiation lobectomy? Clin Imaging 2024; 111:110185. [PMID: 38781614 DOI: 10.1016/j.clinimag.2024.110185] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2023] [Revised: 04/20/2024] [Accepted: 05/08/2024] [Indexed: 05/25/2024]
Abstract
Despite considerable advances in surgical technique, many patients with hepatic malignancies are not operative candidates due to projected inadequate hepatic function following resection. Consequently, the size of the future liver remnant (FLR) is an essential consideration when predicting a patient's likelihood of liver insufficiency following hepatectomy. Since its initial description 30 years ago, portal vein embolization has become the standard of care for augmenting the size and function of the FLR preoperatively. However, new minimally invasive techniques have been developed to improve surgical candidacy, chief among them liver venous deprivation and radiation lobectomy. The purpose of this review is to discuss the status of preoperative liver augmentation prior to resection of hepatocellular carcinoma with a focus on these three techniques, highlighting the distinctions between them and suggesting directions for future investigation.
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Affiliation(s)
- Shin Mei Chan
- Department of Radiology & Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA; Department of Radiology and Biomedical Imaging, Section of Interventional Radiology, Yale School of Medicine, New Haven, CT, USA
| | - Joshua Cornman-Homonoff
- Department of Radiology and Biomedical Imaging, Section of Interventional Radiology, Yale School of Medicine, New Haven, CT, USA
| | - Pierleone Lucatelli
- Department of Radiological, Oncological, and Pathological Sciences, Sapienza University of Rome, Rome, Italy
| | - David C Madoff
- Department of Radiology and Biomedical Imaging, Section of Interventional Radiology, Yale School of Medicine, New Haven, CT, USA; Department of Medicine, Section of Medical Oncology, Yale School of Medicine, New Haven, CT, USA; Department of Surgery, Section of Surgical Oncology, Yale School of Medicine, New Haven, CT, USA.
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Guo Q, Wang ML, Zhong K, Li JL, Jiang TM, Wen H, Aji T, Shao YM. Portal vein embolization combined with ex vivo liver resection and autotransplantation: A novel treatment strategy for end-stage and metastatic hepatic alveolar echinococcosis. Hepatobiliary Pancreat Dis Int 2024; 23:210-216. [PMID: 37295974 DOI: 10.1016/j.hbpd.2023.06.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Accepted: 05/24/2023] [Indexed: 06/12/2023]
Affiliation(s)
- Qiang Guo
- Department of Hepatobiliary and Echinococcosis Surgery, Digestive and Vascular Surgery Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China; Clinical Medical Research Center of Echinococcosis and Hepatobiliary Disease of Xinjiang Uygur Autonomous Region, Urumqi 830054, China
| | - Mao-Lin Wang
- Department of Hepatobiliary and Echinococcosis Surgery, Digestive and Vascular Surgery Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China; Clinical Medical Research Center of Echinococcosis and Hepatobiliary Disease of Xinjiang Uygur Autonomous Region, Urumqi 830054, China
| | - Kai Zhong
- Department of Hepatobiliary and Echinococcosis Surgery, Digestive and Vascular Surgery Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China; Clinical Medical Research Center of Echinococcosis and Hepatobiliary Disease of Xinjiang Uygur Autonomous Region, Urumqi 830054, China
| | - Jia-Long Li
- Department of Hepatobiliary and Echinococcosis Surgery, Digestive and Vascular Surgery Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China; Clinical Medical Research Center of Echinococcosis and Hepatobiliary Disease of Xinjiang Uygur Autonomous Region, Urumqi 830054, China
| | - Tie-Min Jiang
- Department of Hepatobiliary and Echinococcosis Surgery, Digestive and Vascular Surgery Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China; Clinical Medical Research Center of Echinococcosis and Hepatobiliary Disease of Xinjiang Uygur Autonomous Region, Urumqi 830054, China
| | - Hao Wen
- Department of Hepatobiliary and Echinococcosis Surgery, Digestive and Vascular Surgery Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China; Clinical Medical Research Center of Echinococcosis and Hepatobiliary Disease of Xinjiang Uygur Autonomous Region, Urumqi 830054, China; State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, Urumqi 830054, China
| | - Tuerganaili Aji
- Department of Hepatobiliary and Echinococcosis Surgery, Digestive and Vascular Surgery Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China; Clinical Medical Research Center of Echinococcosis and Hepatobiliary Disease of Xinjiang Uygur Autonomous Region, Urumqi 830054, China
| | - Ying-Mei Shao
- Department of Hepatobiliary and Echinococcosis Surgery, Digestive and Vascular Surgery Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China; Clinical Medical Research Center of Echinococcosis and Hepatobiliary Disease of Xinjiang Uygur Autonomous Region, Urumqi 830054, China.
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de Mathelin P, Noblet V, Trog A, Paul C, Cusumano C, Faitot F, Bachellier P, Addeo P. Volumetric Remodeling of the Left Liver After Right Hepatectomy: Analysis of Factors Predicting Degree of Hypertrophy and Post-hepatectomy Liver Failure. J Gastrointest Surg 2023; 27:2752-2762. [PMID: 37884754 DOI: 10.1007/s11605-023-05804-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2023] [Accepted: 08/04/2023] [Indexed: 10/28/2023]
Abstract
BACKGROUND This study investigated the volumetric remodeling of the left liver after right hepatectomy looking for factors predicting the degree of hypertrophy and severe post-hepatectomy liver failure (PHLF). METHODS In a cohort of 121 right hepatectomies, we performed CT volumetrics study of the future left liver remnant (FLR) preoperatively and postoperatively. Factors influencing FLR degree of hypertrophy and severe PHLF were identified by multivariate analysis. RESULTS After right hepatectomy, the mean degree of hypertrophy and kinetic growth rate of the left liver remnant were 25% and 3%/day respectively. The mean liver volume recovery rate was 77%. Liver remodeling volume was distributed for 79% on segments 2 and 3 and 21% on the segment 4 (p<0.001). Women showed a greater hypertrophy of segments 2 and 3 compared with men (p=0.002). The degree of hypertrophy of segment 4 was lower in case of middle hepatic vein resection (p=0.004). Left liver remnant kinetic growth rate was associated with the standardized future liver remnant (sFLR) (p<0.001) and a two-stage hepatectomy (p=0.023). Severe PHLF were predicted by intraoperative transfusion (p=0.009), biliary tumors (p=0.013), and male gender (p=0.022). CONCLUSIONS Volumetric remodeling of the left liver after right hepatectomy is not uniform and is mainly influenced by gender and sacrifice of middle hepatic vein. Male gender, intraoperative transfusion, and biliary tumors increase the risk of postoperative liver failure after right hepatectomy.
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Affiliation(s)
- Pierre de Mathelin
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Pôle des Pathologies Digestives, Hépatiques et de la Transplantation, Hôpital de Hautepierre-Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, France 1, Avenue Moliere, 67098, Strasbourg, France
- ICube, Université de Strasbourg, CNRS UMR 7357, Illkirch, France
| | - Vincent Noblet
- ICube, Université de Strasbourg, CNRS UMR 7357, Illkirch, France
| | - Arnaud Trog
- ICube, Université de Strasbourg, CNRS UMR 7357, Illkirch, France
| | - Chloé Paul
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Pôle des Pathologies Digestives, Hépatiques et de la Transplantation, Hôpital de Hautepierre-Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, France 1, Avenue Moliere, 67098, Strasbourg, France
| | - Caterina Cusumano
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Pôle des Pathologies Digestives, Hépatiques et de la Transplantation, Hôpital de Hautepierre-Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, France 1, Avenue Moliere, 67098, Strasbourg, France
| | - François Faitot
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Pôle des Pathologies Digestives, Hépatiques et de la Transplantation, Hôpital de Hautepierre-Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, France 1, Avenue Moliere, 67098, Strasbourg, France
- ICube, Université de Strasbourg, CNRS UMR 7357, Illkirch, France
| | - Philippe Bachellier
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Pôle des Pathologies Digestives, Hépatiques et de la Transplantation, Hôpital de Hautepierre-Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, France 1, Avenue Moliere, 67098, Strasbourg, France
| | - Pietro Addeo
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Pôle des Pathologies Digestives, Hépatiques et de la Transplantation, Hôpital de Hautepierre-Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, France 1, Avenue Moliere, 67098, Strasbourg, France.
- ICube, Université de Strasbourg, CNRS UMR 7357, Illkirch, France.
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Unterweger IA, Klepstad J, Hannezo E, Lundegaard PR, Trusina A, Ober EA. Lineage tracing identifies heterogeneous hepatoblast contribution to cell lineages and postembryonic organ growth dynamics. PLoS Biol 2023; 21:e3002315. [PMID: 37792696 PMCID: PMC10550115 DOI: 10.1371/journal.pbio.3002315] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Accepted: 08/29/2023] [Indexed: 10/06/2023] Open
Abstract
To meet the physiological demands of the body, organs need to establish a functional tissue architecture and adequate size as the embryo develops to adulthood. In the liver, uni- and bipotent progenitor differentiation into hepatocytes and biliary epithelial cells (BECs), and their relative proportions, comprise the functional architecture. Yet, the contribution of individual liver progenitors at the organ level to both fates, and their specific proportion, is unresolved. Combining mathematical modelling with organ-wide, multispectral FRaeppli-NLS lineage tracing in zebrafish, we demonstrate that a precise BEC-to-hepatocyte ratio is established (i) fast, (ii) solely by heterogeneous lineage decisions from uni- and bipotent progenitors, and (iii) independent of subsequent cell type-specific proliferation. Extending lineage tracing to adulthood determined that embryonic cells undergo spatially heterogeneous three-dimensional growth associated with distinct environments. Strikingly, giant clusters comprising almost half a ventral lobe suggest lobe-specific dominant-like growth behaviours. We show substantial hepatocyte polyploidy in juveniles representing another hallmark of postembryonic liver growth. Our findings uncover heterogeneous progenitor contributions to tissue architecture-defining cell type proportions and postembryonic organ growth as key mechanisms forming the adult liver.
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Affiliation(s)
- Iris. A. Unterweger
- University of Copenhagen, NNF Center for Stem Cell Biology (DanStem), Copenhagen N, Denmark
- University of Copenhagen, Department of Biomedical Sciences, Copenhagen N, Denmark
| | - Julie Klepstad
- Niels Bohr Institute, University of Copenhagen, Copenhagen, Denmark
- Andalusian Center for Developmental Biology, CSIC, University Pablo de Olavide, Seville, Spain
| | - Edouard Hannezo
- Institute of Science and Technology, Klosterneuburg, Austria
| | - Pia R. Lundegaard
- University of Copenhagen, Department of Biomedical Sciences, Copenhagen N, Denmark
| | - Ala Trusina
- Niels Bohr Institute, University of Copenhagen, Copenhagen, Denmark
| | - Elke A. Ober
- University of Copenhagen, NNF Center for Stem Cell Biology (DanStem), Copenhagen N, Denmark
- University of Copenhagen, Department of Biomedical Sciences, Copenhagen N, Denmark
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Tithof J, Pruett TL, Rao JS. Lumped parameter liver simulation to predict acute haemodynamic alterations following partial resections. J R Soc Interface 2023; 20:20230444. [PMID: 37876272 PMCID: PMC10598422 DOI: 10.1098/rsif.2023.0444] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Accepted: 10/02/2023] [Indexed: 10/26/2023] Open
Abstract
Partial liver resections are routinely performed in living donor liver transplantation and to debulk tumours in liver malignancies, but surgical decisions on vessel reconstruction for adequate inflow and outflow are challenging. Pre-operative evaluation is often limited to radiological imaging, which fails to account for post-resection haemodynamic alterations. Substantial evidence suggests post-surgical increase in local volume flow rate enhances shear stress, signalling hepatic regeneration, but excessive shear stress has been postulated to result in small for size syndrome and liver failure. Predicting haemodynamic alterations throughout the liver is particularly challenging due to the dendritic architecture of the vasculature, spanning several orders of magnitude in diameter. Therefore, we developed a mathematical lumped parameter model with realistic heterogeneities capturing inflow/outflow of the human liver to simulate acute perfusion alterations following surgical resection. Our model is parametrized using clinical measurements, relies on a single free parameter and accurately captures established perfusion characteristics. We quantify acute changes in volume flow rate, flow speed and wall shear stress following variable, realistic liver resections and make comparisons with the intact liver. Our numerical model runs in minutes and can be adapted to patient-specific anatomy, providing a novel computational tool aimed at assisting pre- and intra-operative surgical decisions for liver resections.
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Affiliation(s)
- Jeffrey Tithof
- Department of Mechanical Engineering, University of Minnesota, 111 Church Street SE, Minneapolis, MN 55455, USA
| | - Timothy L. Pruett
- Division of Solid Organ Transplantation, Department of Surgery, University of Minnesota, Minneapolis, MN, USA
| | - Joseph Sushil Rao
- Division of Solid Organ Transplantation, Department of Surgery, University of Minnesota, Minneapolis, MN, USA
- Schulze Diabetes Institute, Department of Surgery, University of Minnesota, 420 Delaware Street SE, Minneapolis, MN 55455, USA
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Uchida Y, Imai Y, Tsuji S, Uemura H, Kouyama JI, Naiki K, Ando S, Sugawara K, Nakao M, Nakayama N, Mizuno S, Tomiya T, Mochida S. Significance of portal venous blood flow as a factor to determine liver function in patients with decompensated cirrhosis due to hepatitis C virus infection following achievement of sustained viral response by sofosbuvir plus velpatasvir. Hepatol Res 2023; 53:815-828. [PMID: 37243512 DOI: 10.1111/hepr.13926] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Revised: 05/02/2023] [Accepted: 05/18/2023] [Indexed: 05/29/2023]
Abstract
AIM To determine the outcomes concerning portal venous blood flow and portosystemic shunts in patients with decompensated cirrhosis due to hepatitis C virus (HCV) infection who achieved sustained viral response (SVR) following antiviral therapy. METHODS Portal hypertension-related events and liver function were evaluated in 24 patients achieving SVR following sofosbuvir plus velpatasvir therapy. RESULTS Serum albumin level (median; g/dL) increased from 2.9 at baseline to 3.5 at 12 weeks after the end of treatment (EOT) (p = 0.005), while liver volumes (cm3 ) decreased from 1260 to 1150 (p = 0.0002). Portal hypertension-related events developed in 10 patients (41.7%), and the cumulative occurrence rates after the EOT were 29.2%, 33.3%, and 46.1% at 24, 48, and 96 weeks, respectively. Multivariate logistic regression analysis revealed that the maximal diameter of the shunts (p = 0.0235) was associated with the development of the events, with a cut-off value of 8.3 mm (p = 0.0105). Meanwhile, multiple linear regression analysis revealed that portal venous blood flow, liver volume, serum albumin, and bilirubin levels at baseline were associated with serum albumin levels at 12 weeks after EOT (p = 0.0019, p = 0.0154, p = 0.0010, and p = 0.0350, respectively). CONCLUSION In patients with decompensated cirrhosis due to HCV infection, the baseline portal venous blood flow and liver volume and function were predictive of liver function following SVR, while the maximal diameter of portosystemic shunts predicted the occurrence of portal hypertension-related events.
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Affiliation(s)
- Yoshihito Uchida
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, Moroyama, Japan
| | - Yukinori Imai
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, Moroyama, Japan
| | - Shohei Tsuji
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, Moroyama, Japan
| | - Hayato Uemura
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, Moroyama, Japan
| | - Jun-Ichi Kouyama
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, Moroyama, Japan
| | - Kayoko Naiki
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, Moroyama, Japan
| | - Satsuki Ando
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, Moroyama, Japan
| | - Kayoko Sugawara
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, Moroyama, Japan
| | - Masamitsu Nakao
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, Moroyama, Japan
| | - Nobuaki Nakayama
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, Moroyama, Japan
| | - Suguru Mizuno
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, Moroyama, Japan
| | - Tomoaki Tomiya
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, Moroyama, Japan
| | - Satoshi Mochida
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, Moroyama, Japan
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Endesh N, Chuntharpursat‐Bon E, Revill C, Yuldasheva NY, Futers TS, Parsonage G, Humphreys N, Adamson A, Morley LC, Cubbon RM, Prasad KR, Foster R, Lichtenstein L, Beech DJ. Independent endothelial functions of PIEZO1 and TRPV4 in hepatic portal vein and predominance of PIEZO1 in mechanical and osmotic stress. Liver Int 2023; 43:2026-2038. [PMID: 37349903 PMCID: PMC10946873 DOI: 10.1111/liv.15646] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Revised: 04/27/2023] [Accepted: 05/31/2023] [Indexed: 06/24/2023]
Abstract
BACKGROUND & AIMS PIEZO1 and TRPV4 are mechanically and osmotically regulated calcium-permeable channels. The aim of this study was to determine the relevance and relationship of these channels in the contractile tone of the hepatic portal vein, which experiences mechanical and osmotic variations as it delivers blood to the liver from the intestines, gallbladder, pancreas and spleen. METHODS Wall tension was measured in freshly dissected portal veins from adult male mice, which were genetically unmodified or modified for either a non-disruptive tag in native PIEZO1 or endothelial-specific PIEZO1 deletion. Pharmacological agents were used to activate or inhibit PIEZO1, TRPV4 and associated pathways, including Yoda1 and Yoda2 for PIEZO1 and GSK1016790A for TRPV4 agonism, respectively. RESULTS PIEZO1 activation leads to nitric oxide synthase- and endothelium-dependent relaxation of the portal vein. TRPV4 activation causes contraction, which is also endothelium-dependent but independent of nitric oxide synthase. The TRPV4-mediated contraction is suppressed by inhibitors of phospholipase A2 and cyclooxygenases and mimicked by prostaglandin E2 , suggesting mediation by arachidonic acid metabolism. TRPV4 antagonism inhibits the effect of agonising TRPV4 but not PIEZO1. Increased wall stretch and hypo-osmolality inhibit TRPV4 responses while lacking effects on or amplifying PIEZO1 responses. CONCLUSIONS The portal vein contains independently functioning PIEZO1 channels and TRPV4 channels in the endothelium, the pharmacological activation of which leads to opposing effects of vessel relaxation (PIEZO1) and contraction (TRPV4). In mechanical and osmotic strain, the PIEZO1 mechanism dominates. Modulators of these channels could present important new opportunities for manipulating liver perfusion and regeneration in disease and surgical procedures.
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Affiliation(s)
| | | | | | | | | | | | - Neil Humphreys
- Faculty of Biology, Medicine and HealthUniversity of ManchesterManchesterUK
| | - Antony Adamson
- Faculty of Biology, Medicine and HealthUniversity of ManchesterManchesterUK
| | | | | | - K. Raj Prasad
- Department of Hepatobiliary and Transplant SurgerySt James's University HospitalLeedsUK
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12
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McConnell MJ, Kostallari E, Ibrahim SH, Iwakiri Y. The evolving role of liver sinusoidal endothelial cells in liver health and disease. Hepatology 2023; 78:649-669. [PMID: 36626620 PMCID: PMC10315420 DOI: 10.1097/hep.0000000000000207] [Citation(s) in RCA: 35] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Accepted: 11/25/2022] [Indexed: 01/12/2023]
Abstract
LSECs are a unique population of endothelial cells within the liver and are recognized as key regulators of liver homeostasis. LSECs also play a key role in liver disease, as dysregulation of their quiescent phenotype promotes pathological processes within the liver including inflammation, microvascular thrombosis, fibrosis, and portal hypertension. Recent technical advances in single-cell analysis have characterized distinct subpopulations of the LSECs themselves with a high resolution and defined their gene expression profile and phenotype, broadening our understanding of their mechanistic role in liver biology. This article will review 4 broad advances in our understanding of LSEC biology in general: (1) LSEC heterogeneity, (2) LSEC aging and senescence, (3) LSEC role in liver regeneration, and (4) LSEC role in liver inflammation and will then review the role of LSECs in various liver pathologies including fibrosis, DILI, alcohol-associated liver disease, NASH, viral hepatitis, liver transplant rejection, and ischemia reperfusion injury. The review will conclude with a discussion of gaps in knowledge and areas for future research.
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Affiliation(s)
- Matthew J. McConnell
- Section of Digestive Disease, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut
| | | | - Samar H. Ibrahim
- Division of Gastroenterology, Mayo Clinic, Rochester, MN
- Division of Pediatric Gastroenterology, Mayo Clinic, Rochester, MN
| | - Yasuko Iwakiri
- Section of Digestive Disease, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut
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13
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Cooper SA, Kostallari E, Shah VH. Angiocrine Signaling in Sinusoidal Health and Disease. Semin Liver Dis 2023; 43:245-257. [PMID: 37442155 PMCID: PMC10798369 DOI: 10.1055/a-2128-5907] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/15/2023]
Abstract
Liver sinusoidal endothelial cells (LSECs) are key players in maintaining hepatic homeostasis. They also play crucial roles during liver injury by communicating with liver cell types as well as immune cells and promoting portal hypertension, fibrosis, and inflammation. Cutting-edge technology, such as single cell and spatial transcriptomics, have revealed the existence of distinct LSEC subpopulations with a clear zonation in the liver. The signals released by LSECs are commonly called "angiocrine signaling." In this review, we summarize the role of angiocrine signaling in health and disease, including zonation in healthy liver, regeneration, fibrosis, portal hypertension, nonalcoholic fatty liver disease, alcohol-associated liver disease, aging, drug-induced liver injury, and ischemia/reperfusion, as well as potential therapeutic advances. In conclusion, sinusoidal endotheliopathy is recognized in liver disease and promising preclinical studies are paving the path toward LSEC-specific pharmacotherapies.
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Affiliation(s)
- Shawna A. Cooper
- Biochemistry and Molecular Biology Graduate Program, Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, Minnesota
| | - Enis Kostallari
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Vijay H. Shah
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
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14
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Wu Y, Li N, Shu X, Li W, Zhang X, Lü D, Long M. Biomechanics in liver regeneration after partial hepatectomy. Front Bioeng Biotechnol 2023; 11:1165651. [PMID: 37214300 PMCID: PMC10196191 DOI: 10.3389/fbioe.2023.1165651] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Accepted: 04/18/2023] [Indexed: 05/24/2023] Open
Abstract
The liver is a complicated organ within the body that performs wide-ranging and vital functions and also has a unique regenerative capacity after hepatic tissue injury and cell loss. Liver regeneration from acute injury is always beneficial and has been extensively studied. Experimental models including partial hepatectomy (PHx) reveal that extracellular and intracellular signaling pathways can help the liver recover to its equivalent size and weight prior to an injury. In this process, mechanical cues possess immediate and drastic changes in liver regeneration after PHx and also serve as main triggering factors and significant driving forces. This review summarized the biomechanics progress in liver regeneration after PHx, mainly focusing on PHx-based hemodynamics changes in liver regeneration and the decoupling of mechanical forces in hepatic sinusoids including shear stress, mechanical stretch, blood pressure, and tissue stiffness. Also discussed were the potential mechanosensors, mechanotransductive pathways, and mechanocrine responses under varied mechanical loading in vitro. Further elucidating these mechanical concepts in liver regeneration helps establish a comprehensive understanding of the biochemical factors and mechanical cues in this process. Proper adjustment of mechanical loading within the liver might preserve and restore liver functions in clinical settings, serving as an effective therapy for liver injury and diseases.
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Affiliation(s)
- Yi Wu
- Center for Biomechanics and Bioengineering, Beijing Key Laboratory of Engineered Construction and Mechanobiology and Key Laboratory of Microgravity (National Microgravity Laboratory), Institute of Mechanics, Chinese Academy of Sciences, Beijing, China
- School of Engineering Sciences, University of Chinese Academy of Sciences, Beijing, China
| | - Ning Li
- Center for Biomechanics and Bioengineering, Beijing Key Laboratory of Engineered Construction and Mechanobiology and Key Laboratory of Microgravity (National Microgravity Laboratory), Institute of Mechanics, Chinese Academy of Sciences, Beijing, China
- School of Engineering Sciences, University of Chinese Academy of Sciences, Beijing, China
| | - Xinyu Shu
- Center for Biomechanics and Bioengineering, Beijing Key Laboratory of Engineered Construction and Mechanobiology and Key Laboratory of Microgravity (National Microgravity Laboratory), Institute of Mechanics, Chinese Academy of Sciences, Beijing, China
- School of Engineering Sciences, University of Chinese Academy of Sciences, Beijing, China
| | - Wang Li
- Center for Biomechanics and Bioengineering, Beijing Key Laboratory of Engineered Construction and Mechanobiology and Key Laboratory of Microgravity (National Microgravity Laboratory), Institute of Mechanics, Chinese Academy of Sciences, Beijing, China
- School of Engineering Sciences, University of Chinese Academy of Sciences, Beijing, China
| | - Xiaoyu Zhang
- Center for Biomechanics and Bioengineering, Beijing Key Laboratory of Engineered Construction and Mechanobiology and Key Laboratory of Microgravity (National Microgravity Laboratory), Institute of Mechanics, Chinese Academy of Sciences, Beijing, China
- School of Engineering Sciences, University of Chinese Academy of Sciences, Beijing, China
| | - Dongyuan Lü
- Center for Biomechanics and Bioengineering, Beijing Key Laboratory of Engineered Construction and Mechanobiology and Key Laboratory of Microgravity (National Microgravity Laboratory), Institute of Mechanics, Chinese Academy of Sciences, Beijing, China
- School of Engineering Sciences, University of Chinese Academy of Sciences, Beijing, China
| | - Mian Long
- Center for Biomechanics and Bioengineering, Beijing Key Laboratory of Engineered Construction and Mechanobiology and Key Laboratory of Microgravity (National Microgravity Laboratory), Institute of Mechanics, Chinese Academy of Sciences, Beijing, China
- School of Engineering Sciences, University of Chinese Academy of Sciences, Beijing, China
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15
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Masuo H, Shimizu A, Motoyama H, Kubota K, Notake T, Yoshizawa T, Hosoda K, Yasukawa K, Kobayashi A, Soejima Y. Impact of endothelial nitric oxide synthase activation on accelerated liver regeneration in a rat ALPPS model. World J Gastroenterol 2023; 29:867-878. [PMID: 36816620 PMCID: PMC9932423 DOI: 10.3748/wjg.v29.i5.867] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Revised: 12/07/2022] [Accepted: 01/12/2023] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Although the associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) induces more rapid liver regeneration than portal vein embolization, the mechanism remains unclear.
AIM To assess the influence of inflammatory cytokines and endothelial nitric oxide synthase (eNOS) activation on liver regeneration in ALPPS.
METHODS The future liver remnant/body weight (FLR/BW) ratio, hepatocyte proliferation, inflammatory cytokine expression, and activation of the Akt-eNOS pathway were evaluated in rat ALPPS and portal vein ligation (PVL) models. Hepatocyte proliferation was assessed based on Ki-67 expression, which was confirmed using immunohistochemistry. The serum concentrations of inflammatory cytokines were measured using enzyme linked immune-solvent assays. The Akt-eNOS pathway was assessed using western blotting. To explore the role of inflammatory cytokines and NO, Kupffer cell inhibitor gadolinium chloride (GdCl3), NOS inhibitor N-nitro-arginine methyl ester (L-NAME), and NO enhancer molsidomine were administered intraperitoneally.
RESULTS The ALPPS group showed significant FLR regeneration (FLR/BW: 1.60% ± 0.08%, P < 0.05) compared with that observed in the PVL group (1.33% ± 0.11%) 48 h after surgery. In the ALPPS group, serum interleukin-6 expression was suppressed using GdCl3 to the same extent as that in the PVL group. However, the FLR/BW ratio and Ki-67 labeling index were significantly higher in the ALPPS group administered GdCl3 (1.72% ± 0.19%, P < 0.05; 22.25% ± 1.30%, P < 0.05) than in the PVL group (1.33% ± 0.11% and 12.78% ± 1.55%, respectively). Phospho-Akt Ser473 and phospho-eNOS Ser1177 levels were enhanced in the ALPPS group compared with those in the PVL group. There was no difference between the ALPPS group treated with L-NAME and the PVL group in the FLR/BW ratio and Ki-67 labeling index. In the PVL group treated with molsidomine, the FLR/BW ratio and Ki-67 labeling index increased to the same level as in the ALPPS group.
CONCLUSION Early induction of inflammatory cytokines may not be pivotal for accelerated FLR regeneration after ALPPS, whereas Akt-eNOS pathway activation may contribute to accelerated regeneration of the FLR.
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Affiliation(s)
- Hitoshi Masuo
- Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, Matsumoto 390-8621, Japan
| | - Akira Shimizu
- Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, Matsumoto 390-8621, Japan
| | - Hiroaki Motoyama
- Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, Matsumoto 390-8621, Japan
| | - Koji Kubota
- Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, Matsumoto 390-8621, Japan
| | - Tsuyoshi Notake
- Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, Matsumoto 390-8621, Japan
| | - Takahiro Yoshizawa
- Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, Matsumoto 390-8621, Japan
| | - Kiyotaka Hosoda
- Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, Matsumoto 390-8621, Japan
| | - Koya Yasukawa
- Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, Matsumoto 390-8621, Japan
| | - Akira Kobayashi
- Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, Matsumoto 390-8621, Japan
| | - Yuji Soejima
- Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, Matsumoto 390-8621, Japan
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16
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Hsiao HY, Mackert GA, Chang YC, Liu JW, Chang FCS, Huang JJ. In vivo vascularized scaffold with different shear-exposed models for lymphatic tissue regeneration. J Tissue Eng 2023; 14:20417314231196212. [PMID: 37661967 PMCID: PMC10472829 DOI: 10.1177/20417314231196212] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Accepted: 07/31/2023] [Indexed: 09/05/2023] Open
Abstract
Current clinical treatments on lymphedema provide promising results, but also result in donor site morbidities. The establishment of a microenvironment optimized for lymphangiogenesis can be an alternative way to enhance lymphatic tissue formation. Hemodynamic flow stimuli have been confirmed to have an influential effect on angiogenesis in tissue engineering, but not on lymphatic vessel formation. Here, the three in vivo scaffolds generated from different blood stimuli in the subcutaneous layer, in the flow through pedicle, and in an arterio-venous (AV) loop model, were created to investigate potential of lymphangiogenesis of scaffolds containing lymphatic endothelial cells (LECs). Our results indicated that AV loop model displayed better lymphangiogenesis in comparison to the other two models with slower flow or no stimuli. Other than hemodynamic force, the supplement of LECs is required for lymphatic vessel regeneration. The in vivo scaffold generated from AV loop model provides an effective approach for engineering lymphatic tissue in the clinical treatment of lymphedema.
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Affiliation(s)
- Hui-Yi Hsiao
- Department of Biomedical Sciences, Chang Gung University, Taoyuan
- Center for Tissue Engineering, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan
| | - Gina Alicia Mackert
- Division of Reconstructive Microsurgery, Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan
- Department of Hand, Plastic and Reconstructive Surgery, Burn Center, BG Trauma Center Ludwigshafen, Department of Hand and Plastic Surgery, University of Heidelberg, Ludwigshafen, Germany
| | - Yung-Chun Chang
- Center for Tissue Engineering, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan
- Division of Reconstructive Microsurgery, Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan
| | - Jia-Wei Liu
- Center for Tissue Engineering, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan
- Division of Reconstructive Microsurgery, Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan
| | - Frank Chun-Shin Chang
- Division of Reconstructive Microsurgery, Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan
- College of Medicine, Chang Gung University, Taoyuan
| | - Jung-Ju Huang
- Center for Tissue Engineering, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan
- Division of Reconstructive Microsurgery, Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan
- College of Medicine, Chang Gung University, Taoyuan
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17
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Shu W, Yang M, Yang J, Lin S, Wei X, Xu X. Cellular crosstalk during liver regeneration: unity in diversity. Cell Commun Signal 2022; 20:117. [PMID: 35941604 PMCID: PMC9358812 DOI: 10.1186/s12964-022-00918-z] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Accepted: 06/08/2022] [Indexed: 11/27/2022] Open
Abstract
The liver is unique in its ability to regenerate from a wide range of injuries and diseases. Liver regeneration centers around hepatocyte proliferation and requires the coordinated actions of nonparenchymal cells, including biliary epithelial cells, liver sinusoidal endothelial cells, hepatic stellate cells and kupffer cells. Interactions among various hepatocyte and nonparenchymal cells populations constitute a sophisticated regulatory network that restores liver mass and function. In addition, there are two different ways of liver regeneration, self-replication of liver epithelial cells and transdifferentiation between liver epithelial cells. The interactions among cell populations and regenerative microenvironment in the two modes are distinct. Herein, we first review recent advances in the interactions between hepatocytes and surrounding cells and among nonparenchymal cells in the context of liver epithelial cell self-replication. Next, we discuss the crosstalk of several cell types in the context of liver epithelial transdifferentiation, which is also crucial for liver regeneration.
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Video abstract
- Wenzhi Shu
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China.,Institute of Organ Transplantation, Zhejiang University, Hangzhou, 310003, China.,NHC Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou, 310003, China.,Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, 310024, China.,Program in Clinical Medicine, Zhejiang University School of Medicine, Hangzhou, People's Republic of China
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- Mengfan Yang
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China.,Institute of Organ Transplantation, Zhejiang University, Hangzhou, 310003, China.,NHC Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou, 310003, China.,Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, 310024, China
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- Jiayin Yang
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, Sichuan, People's Republic of China
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- Shengda Lin
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China.,Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, 310058, Zhejiang, China
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- Xuyong Wei
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China. .,Institute of Organ Transplantation, Zhejiang University, Hangzhou, 310003, China. .,NHC Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou, 310003, China. .,Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, 310024, China.
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- Xiao Xu
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China. .,Institute of Organ Transplantation, Zhejiang University, Hangzhou, 310003, China. .,NHC Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou, 310003, China. .,Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, 310024, China.
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18
Cassese G, Han HS, Al Farai A, Guiu B, Troisi RI, Panaro F. Future remnant liver optimization: preoperative assessment, volume augmentation procedures and management of PVE failure.
Minerva Surg 2022;
77:368-379. [PMID:
35332767 DOI:
10.23736/s2724-5691.22.09541-7]
[Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Surgery is the cornerstone treatment for patients with primary or metastatic hepatic tumors. Thanks to surgical and anesthetic technological advances, current indications for liver resections have been significantly expanded to include any patient in whom all disease can be resected with a negative margin (R0) while preserving an adequate future residual liver (FRL). Posthepatectomy liver failure (PHLF) is still a feared complication following major liver surgery, associated with high morbidity, mortality and cost implications. PHLF is mainly linked to both the size and quality of the FRL. Significant advances have been made in detailed preoperative assessment to predict and mitigate this complication, even if an ideal methodology has yet to be defined. Several procedures have been described to induce hypertrophy of the FRL when needed. Each technique has its advantages and limitations, and among them portal vein embolization (PVE) is still considered the standard of care. About 20% of patients after PVE fail to undergo the scheduled hepatectomy, and newer secondary procedures, such as segment 4 embolization, ALPPS and HVE, have been proposed as salvage strategies. The aim of this review was to discuss the current modalities available and new perspectives in the optimization of FRL in patients undergoing major liver resection.
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Affiliation(s)
- Gianluca Cassese
- Minimally Invasive and Robotic HPB Unit, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
- Seoul National University College of Medicine, Department of Surgery, Seoul National University Bundang Hospital, Seoul, South Korea
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- Ho-Seong Han
- Seoul National University College of Medicine, Department of Surgery, Seoul National University Bundang Hospital, Seoul, South Korea
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- Abdallah Al Farai
- Department of Surgical Oncology, Sultan Qaboos Comprehensive Cancer Care and Research Center, Muscat, Oman
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- Boris Guiu
- Department of Radiology, Montpellier University Hospital, Montpellier, France
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- Roberto I Troisi
- Minimally Invasive and Robotic HPB Unit, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
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- Fabrizio Panaro
- Unit of Digestive Surgery and Liver Transplantation, Montpellier University Hospital School of Medicine, Montpellier University Hospital, Montpellier-Nimes University, Montpellier, France -
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19
Abstract
Liver regeneration is a well-orchestrated process that is typically studied in animal models. Although previous animal studies have offered many insights into liver regeneration, human biology is less well understood. To this end, we developed a three-dimensional (3D) platform called structurally vascularized hepatic ensembles for analyzing regeneration (SHEAR) to model multiple aspects of human liver regeneration. SHEAR enables control over hemodynamic alterations to mimic those that occur during liver injury and regeneration and supports the administration of biochemical inputs such as cytokines and paracrine interactions with endothelial cells. We found that exposing the endothelium-lined channel to fluid flow led to increased secretion of regeneration-associated factors. Stimulation with relevant cytokines not only amplified the secretory response, but also induced cell-cycle entry of primary human hepatocytes (PHHs) embedded within the device. Further, we identified endothelial-derived mediators that are sufficient to initiate proliferation of PHHs in this context. Collectively, the data presented here underscore the importance of multicellular models that can recapitulate high-level tissue functions and demonstrate that the SHEAR device can be used to discover and validate conditions that promote human liver regeneration.
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20
Savioli G, Ceresa IF, Gori G, Fumoso F, Gri N, Floris V, Varesi A, Martuscelli E, Marchisio S, Longhitano Y, Ricevuti G, Esposito C, Caironi G, Giardini G, Zanza C. Pathophysiology and Therapy of High-Altitude Sickness: Practical Approach in Emergency and Critical Care.
J Clin Med 2022;
11:3937. [PMID:
35887706 PMCID:
PMC9325098 DOI:
10.3390/jcm11143937]
[Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Revised: 06/21/2022] [Accepted: 06/24/2022] [Indexed: 12/26/2022] Open
Abstract
High altitude can be a hostile environment and a paradigm of how environmental factors can determine illness when human biological adaptability is exceeded. This paper aims to provide a comprehensive review of high-altitude sickness, including its epidemiology, pathophysiology, and treatments. The first section of our work defines high altitude and considers the mechanisms of adaptation to it and the associated risk factors for low adaptability. The second section discusses the main high-altitude diseases, highlighting how environmental factors can lead to the loss of homeostasis, compromising important vital functions. Early recognition of clinical symptoms is important for the establishment of the correct therapy. The third section focuses on high-altitude pulmonary edema, which is one of the main high-altitude diseases. With a deeper understanding of the pathogenesis of high-altitude diseases, as well as a reasoned approach to environmental or physical factors, we examine the main high-altitude diseases. Such an approach is critical for the effective treatment of patients in a hostile environment, or treatment in the emergency room after exposure to extreme physical or environmental factors.
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Affiliation(s)
- Gabriele Savioli
- Department of Emergency Medicine and Surgery, IRCCS Fondazione Policlinico San Matteo, 27100 Pavia, Italy;
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- Giulia Gori
- Department of Internal Medicine, University of Pavia, 27100 Pavia, Italy; (G.G.); (F.F.)
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- Federica Fumoso
- Department of Internal Medicine, University of Pavia, 27100 Pavia, Italy; (G.G.); (F.F.)
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- Nicole Gri
- School of Medicine, University of Pavia, 27100 Pavia, Italy; (N.G.); (V.F.); (A.V.)
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- Valentina Floris
- School of Medicine, University of Pavia, 27100 Pavia, Italy; (N.G.); (V.F.); (A.V.)
- Department of Emergency Medicine (ASL AL), San Giacomo Hospital, 15067 Novi Ligure, Italy; (E.M.); (S.M.); (Y.L.)
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- Angelica Varesi
- School of Medicine, University of Pavia, 27100 Pavia, Italy; (N.G.); (V.F.); (A.V.)
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- Ermelinda Martuscelli
- Department of Emergency Medicine (ASL AL), San Giacomo Hospital, 15067 Novi Ligure, Italy; (E.M.); (S.M.); (Y.L.)
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- Sara Marchisio
- Department of Emergency Medicine (ASL AL), San Giacomo Hospital, 15067 Novi Ligure, Italy; (E.M.); (S.M.); (Y.L.)
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- Yaroslava Longhitano
- Department of Emergency Medicine (ASL AL), San Giacomo Hospital, 15067 Novi Ligure, Italy; (E.M.); (S.M.); (Y.L.)
- Foundation “Ospedale Alba-Bra Onlus”, Department of Emergency Medicine, Anesthesia and Critical Care Medicine, Michele and Pietro Ferrero Hospital, 12060 Verduno, Italy
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- Giovanni Ricevuti
- Department of Drug Science, University of Pavia, 27100 Pavia, Italy;
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- Ciro Esposito
- Nephrology and Dialysis Unit, ICS Maugeri, University of Pavia, 27100 Pavia, Italy;
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- Guido Caironi
- Registered Nurse Supporting Prehospital Emergency Service ASST 118, 22100 Como, Italy;
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- Guido Giardini
- Neurology and Stroke Unit, Ospedale Regionale “U.Parini”, 11100 Aosta, Italy;
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- Christian Zanza
- Department of Emergency Medicine (ASL AL), San Giacomo Hospital, 15067 Novi Ligure, Italy; (E.M.); (S.M.); (Y.L.)
- Foundation “Ospedale Alba-Bra Onlus”, Department of Emergency Medicine, Anesthesia and Critical Care Medicine, Michele and Pietro Ferrero Hospital, 12060 Verduno, Italy
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21
Hadjittofi C, Feretis M, Martin J, Harper S, Huguet E. Liver regeneration biology: Implications for liver tumour therapies.
World J Clin Oncol 2021;
12:1101-1156. [PMID:
35070734 PMCID:
PMC8716989 DOI:
10.5306/wjco.v12.i12.1101]
[Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Revised: 06/22/2021] [Accepted: 11/28/2021] [Indexed: 02/06/2023] Open
Abstract
The liver has remarkable regenerative potential, with the capacity to regenerate after 75% hepatectomy in humans and up to 90% hepatectomy in some rodent models, enabling it to meet the challenge of diverse injury types, including physical trauma, infection, inflammatory processes, direct toxicity, and immunological insults. Current understanding of liver regeneration is based largely on animal research, historically in large animals, and more recently in rodents and zebrafish, which provide powerful genetic manipulation experimental tools. Whilst immensely valuable, these models have limitations in extrapolation to the human situation. In vitro models have evolved from 2-dimensional culture to complex 3 dimensional organoids, but also have shortcomings in replicating the complex hepatic micro-anatomical and physiological milieu. The process of liver regeneration is only partially understood and characterized by layers of complexity. Liver regeneration is triggered and controlled by a multitude of mitogens acting in autocrine, paracrine, and endocrine ways, with much redundancy and cross-talk between biochemical pathways. The regenerative response is variable, involving both hypertrophy and true proliferative hyperplasia, which is itself variable, including both cellular phenotypic fidelity and cellular trans-differentiation, according to the type of injury. Complex interactions occur between parenchymal and non-parenchymal cells, and regeneration is affected by the status of the liver parenchyma, with differences between healthy and diseased liver. Finally, the process of termination of liver regeneration is even less well understood than its triggers. The complexity of liver regeneration biology combined with limited understanding has restricted specific clinical interventions to enhance liver regeneration. Moreover, manipulating the fundamental biochemical pathways involved would require cautious assessment, for fear of unintended consequences. Nevertheless, current knowledge provides guiding principles for strategies to optimise liver regeneration potential.
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Affiliation(s)
- Christopher Hadjittofi
- University Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Center, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
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- Michael Feretis
- University Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Center, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
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- Jack Martin
- University Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Center, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
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- Simon Harper
- University Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Center, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
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- Emmanuel Huguet
- University Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Center, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
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22
Kobayashi S. Hepatic pseudolesions caused by alterations in intrahepatic hemodynamics.
World J Gastroenterol 2021;
27:7894-7908. [PMID:
35046619 PMCID:
PMC8678815 DOI:
10.3748/wjg.v27.i46.7894]
[Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 06/23/2021] [Accepted: 11/25/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatic pseudolesion may occur in contrast-enhanced computed tomography and magnetic resonance imaging due to the unique haemodynamic characteristics of the liver. The concept of hepatic arterial buffer response (HABR) has become mainstream for the understanding of the mechanism of the reciprocal effect between hepatic arterial and portal venous flow. And HABR is thought to be significantly related to the occurrence of the abnormal imaging findings on arterial phase of contrast enhanced images, such as hepatic arterial-portal vein shunt and transient hepatic attenuation difference, which mimic hypervascular tumor and may cause clinical problems. Third inflow to the liver also cause hepatic pseudolesion, and some of the cases may show histopathologic change such as focal hyperplasia, focal fatty liver, and focal sparing of fatty liver, and called pseudotumor. To understand these phenomena might be valuable for interpreting the liver imaging findings.
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Affiliation(s)
- Satoshi Kobayashi
- Department of Quantum Medical Technology, Kanazawa University Graduate School of Medical Sciences, Kanazawa 9200942, Ishikawa, Japan
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23
The Role of Farnesoid X Receptor in Accelerated Liver Regeneration in Rats Subjected to ALPPS.
Curr Oncol 2021;
28:5240-5254. [PMID:
34940077 PMCID:
PMC8700148 DOI:
10.3390/curroncol28060438]
[Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Revised: 12/06/2021] [Accepted: 12/07/2021] [Indexed: 11/29/2022] Open
Abstract
Background: the role of bile acid (BA)-induced farnesoid X receptor (Fxr) signaling in liver regeneration following associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) was investigated in a rat model. Methods: Male Wistar rats underwent portal vein ligation (PVL) (n = 30) or ALPPS (n = 30). Animals were sacrificed pre-operatively and at 24, 48, 72, or 168 h after intervention. Regeneration rate, Ki67 index, hemodynamic changes in the hepatic circulation, and BA levels were assessed. Transcriptome analysis of molecular regulators involved in the Fxr signaling pathway, BA transport, and BA production was performed. Results: ALLPS induced more extensive liver regeneration (p < 0.001) and elevation of systemic and portal BA levels (p < 0.05) than PVL. The mRNA levels of proteins participating in hepatic Fxr signaling were comparable between the intervention groups. More profound activation of the intestinal Fxr pathway was observed 24 h after ALPPS compared to PVL. Conclusion: Our study elaborates on a possible linkage between BA-induced Fxr signaling and accelerated liver regeneration induced by ALPPS in rats. ALPPS could trigger liver regeneration via intestinal Fxr signaling cascades instead of hepatic Fxr signaling, thereby deviating from the mechanism of BA-mediated regeneration following one-stage hepatectomy.
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24
Christ B, Collatz M, Dahmen U, Herrmann KH, Höpfl S, König M, Lambers L, Marz M, Meyer D, Radde N, Reichenbach JR, Ricken T, Tautenhahn HM. Hepatectomy-Induced Alterations in Hepatic Perfusion and Function - Toward Multi-Scale Computational Modeling for a Better Prediction of Post-hepatectomy Liver Function.
Front Physiol 2021;
12:733868. [PMID:
34867441 PMCID:
PMC8637208 DOI:
10.3389/fphys.2021.733868]
[Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Accepted: 10/26/2021] [Indexed: 01/17/2023] Open
Abstract
Liver resection causes marked perfusion alterations in the liver remnant both on the organ scale (vascular anatomy) and on the microscale (sinusoidal blood flow on tissue level). These changes in perfusion affect hepatic functions via direct alterations in blood supply and drainage, followed by indirect changes of biomechanical tissue properties and cellular function. Changes in blood flow impose compression, tension and shear forces on the liver tissue. These forces are perceived by mechanosensors on parenchymal and non-parenchymal cells of the liver and regulate cell-cell and cell-matrix interactions as well as cellular signaling and metabolism. These interactions are key players in tissue growth and remodeling, a prerequisite to restore tissue function after PHx. Their dysregulation is associated with metabolic impairment of the liver eventually leading to liver failure, a serious post-hepatectomy complication with high morbidity and mortality. Though certain links are known, the overall functional change after liver surgery is not understood due to complex feedback loops, non-linearities, spatial heterogeneities and different time-scales of events. Computational modeling is a unique approach to gain a better understanding of complex biomedical systems. This approach allows (i) integration of heterogeneous data and knowledge on multiple scales into a consistent view of how perfusion is related to hepatic function; (ii) testing and generating hypotheses based on predictive models, which must be validated experimentally and clinically. In the long term, computational modeling will (iii) support surgical planning by predicting surgery-induced perfusion perturbations and their functional (metabolic) consequences; and thereby (iv) allow minimizing surgical risks for the individual patient. Here, we review the alterations of hepatic perfusion, biomechanical properties and function associated with hepatectomy. Specifically, we provide an overview over the clinical problem, preoperative diagnostics, functional imaging approaches, experimental approaches in animal models, mechanoperception in the liver and impact on cellular metabolism, omics approaches with a focus on transcriptomics, data integration and uncertainty analysis, and computational modeling on multiple scales. Finally, we provide a perspective on how multi-scale computational models, which couple perfusion changes to hepatic function, could become part of clinical workflows to predict and optimize patient outcome after complex liver surgery.
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Affiliation(s)
- Bruno Christ
- Cell Transplantation/Molecular Hepatology Lab, Department of Visceral, Transplant, Thoracic and Vascular Surgery, University of Leipzig Medical Center, Leipzig, Germany
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- Maximilian Collatz
- RNA Bioinformatics and High-Throughput Analysis, Faculty of Mathematics and Computer Science, Friedrich Schiller University Jena, Jena, Germany
- Optisch-Molekulare Diagnostik und Systemtechnologié, Leibniz Institute of Photonic Technology (IPHT), Jena, Germany
- InfectoGnostics Research Campus Jena, Jena, Germany
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- Uta Dahmen
- Experimental Transplantation Surgery, Department of General, Visceral and Vascular Surgery, Jena University Hospital, Jena, Germany
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- Karl-Heinz Herrmann
- Medical Physics Group, Institute of Diagnostic and Interventional Radiology, Jena University Hospital, Jena, Germany
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- Sebastian Höpfl
- Faculty of Engineering Design, Production Engineering and Automotive Engineering, Institute for Systems Theory and Automatic Control, University of Stuttgart, Stuttgart, Germany
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- Matthias König
- Systems Medicine of the Liver Lab, Institute for Theoretical Biology, Humboldt-University Berlin, Berlin, Germany
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- Lena Lambers
- Faculty of Aerospace Engineering and Geodesy, Institute of Mechanics, Structural Analysis and Dynamics, University of Stuttgart, Stuttgart, Germany
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- Manja Marz
- RNA Bioinformatics and High-Throughput Analysis, Faculty of Mathematics and Computer Science, Friedrich Schiller University Jena, Jena, Germany
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- Daria Meyer
- RNA Bioinformatics and High-Throughput Analysis, Faculty of Mathematics and Computer Science, Friedrich Schiller University Jena, Jena, Germany
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- Nicole Radde
- Faculty of Engineering Design, Production Engineering and Automotive Engineering, Institute for Systems Theory and Automatic Control, University of Stuttgart, Stuttgart, Germany
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- Jürgen R. Reichenbach
- Medical Physics Group, Institute of Diagnostic and Interventional Radiology, Jena University Hospital, Jena, Germany
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- Tim Ricken
- Faculty of Aerospace Engineering and Geodesy, Institute of Mechanics, Structural Analysis and Dynamics, University of Stuttgart, Stuttgart, Germany
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- Hans-Michael Tautenhahn
- Department of General, Visceral and Vascular Surgery, Jena University Hospital, Jena, Germany
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25
Huang W, Han N, Du L, Wang M, Chen L, Tang H. A narrative review of liver regeneration-from models to molecular basis.
ANNALS OF TRANSLATIONAL MEDICINE 2021;
9:1705. [PMID:
34988214 PMCID:
PMC8667151 DOI:
10.21037/atm-21-5234]
[Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Accepted: 11/04/2021] [Indexed: 12/11/2022]
Abstract
Objective
To elucidate the characteristics of different liver regeneration animal models, understand the activation signals and mechanisms related to liver regeneration, and obtain a more comprehensive conception of the entire liver regeneration process.
Background
Liver regeneration is one of the most enigmatic and fascinating phenomena of the human organism. Despite suffering significant injuries, the liver still can continue to perform its complex functions through the regeneration system. Although advanced topics on liver regeneration have been proposed; unfortunately, complete regeneration of the liver has not been achieved until now. Therefore, increasing understanding of the liver regenerative process can help improve our treatment of liver failure. It will provide a new sight for the treatment of patients with liver injury in the clinic.
Methods
Literatures on liver regeneration animal models and involved basic research on molecular mechanisms were retrieved to analyze the characteristics of different models and those related to molecular basis.
Conclusions
The process of liver regeneration is complex and intricate, consisting of various and interactive pathways. There is sufficient evidence to demonstrate that liver regeneration is similar between humans and rodents. At the same time, many of the same cytokines, growth factors, and signaling pathways are relevant. There are many gaps in our current knowledge. Understanding of this knowledge will provide more supportive clinical treatment strategies, including small-scale liver transplantation and high-quality regenerative process after surgical resection, and offer possible targets to treat the dysregulation of regeneration that occurs in chronic hepatic diseases and tumors. Current research work, such as the use of animal models as in vivo vectors for high-quality human hepatocytes, represents a unique and significant cutting edge in the field of liver regeneration.
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Affiliation(s)
- Wei Huang
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China.,Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
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- Ning Han
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China.,Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
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- Lingyao Du
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China.,Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
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- Ming Wang
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China.,Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
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- Liyu Chen
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China.,Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
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- Hong Tang
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China.,Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
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26
Hayashi T, Watanabe T, Shibata M, Kumei S, Oe S, Miyagawa K, Honma Y, Harada M. Endoscopic injection sclerotherapy improves liver function compared with endoscopic variceal ligation.
Sci Rep 2021;
11:20479. [PMID:
34650156 PMCID:
PMC8516919 DOI:
10.1038/s41598-021-99855-z]
[Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Accepted: 09/27/2021] [Indexed: 11/30/2022] Open
Abstract
Liver function is a most important prognostic factor in patients with liver cirrhosis. Also, portal hypertension is a fatal complication of liver cirrhosis and variceal treatment is indispensable. However, changes of liver functions after endoscopic variceal treatments are unknown. The aim of this study was to evaluate prognosis and liver functions after endoscopic injection sclerotherapy (EIS) and endoscopic variceal ligation (EVL). A total of liver cirrhotic 103 patients who underwent prophylactic EIS and EVL were enrolled. Overall survival rate was higher in EIS group than EVL group (p = 0.03). Multivariate analysis showed that EIS was a negative factor for death (HR: 0.46, 95% confidence interval: 0.24–0.88, p = 0.02). Liver functions were assessed by blood test taken at before and 3 months after treatment. In EIS group, albumin and prothrombin time improved (p < 0.01), leading to improvement of Child–Pugh score, ALBI score and MELD score (p < 0.05). However, these did not improve in EVL group. EIS was a significant factor related to the elevated value of albumin after treatment in linear regression analysis (estimated regression coefficient: 0.17, 95% confidence interval: 0.05–0.29, p = 0.005). These results revealed that EIS could improve liver functions and prognosis.
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Affiliation(s)
- Tsuguru Hayashi
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan.
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- Tatsuyuki Watanabe
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan
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- Michihiko Shibata
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan
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- Shinsuke Kumei
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan
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- Shinji Oe
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan
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- Koichiro Miyagawa
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan
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- Yuichi Honma
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan
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- Masaru Harada
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan
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27
De Rudder M, Dili A, Stärkel P, Leclercq IA. Critical Role of LSEC in Post-Hepatectomy Liver Regeneration and Failure.
Int J Mol Sci 2021;
22:8053. [PMID:
34360818 PMCID:
PMC8347197 DOI:
10.3390/ijms22158053]
[Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Revised: 07/20/2021] [Accepted: 07/24/2021] [Indexed: 02/07/2023] Open
Abstract
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.
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Affiliation(s)
- Maxime De Rudder
- Laboratory of Hepato-Gastroenterology, Institute of Experimental and Clinical Research, UCLouvain, 1200 Brussels, Belgium; (M.D.R.); (A.D.); (P.S.)
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- Alexandra Dili
- Laboratory of Hepato-Gastroenterology, Institute of Experimental and Clinical Research, UCLouvain, 1200 Brussels, Belgium; (M.D.R.); (A.D.); (P.S.)
- HPB Surgery Unit, Centre Hospitalier Universitaire UCL Namur, Site Mont-Godinne, 5530 Yvoir, Belgium
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- Peter Stärkel
- Laboratory of Hepato-Gastroenterology, Institute of Experimental and Clinical Research, UCLouvain, 1200 Brussels, Belgium; (M.D.R.); (A.D.); (P.S.)
- Department of Hepato-Gastroenterology, Cliniques Universitaires Saint-Luc, 1200 Brussels, Belgium
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- Isabelle A. Leclercq
- Laboratory of Hepato-Gastroenterology, Institute of Experimental and Clinical Research, UCLouvain, 1200 Brussels, Belgium; (M.D.R.); (A.D.); (P.S.)
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28
Memeo R, Conticchio M, Deshayes E, Nadalin S, Herrero A, Guiu B, Panaro F. Optimization of the future remnant liver: review of the current strategies in Europe.
Hepatobiliary Surg Nutr 2021;
10:350-363. [PMID:
34159162 DOI:
10.21037/hbsn-20-394]
[Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Liver resection still represent the treatment of choice for liver malignancies, but in some cases inadequate future remnant liver (FRL) can lead to post hepatectomy liver failure (PHLF) that still represents the most common cause of death after hepatectomy. Several strategies in recent era have been developed in order to generate a compensatory hypertrophy of the FRL, reducing the risk of post hepatectomy liver failure. Portal vein embolization, portal vein ligation, and ALLPS are the most popular techniques historically adopted up to now. The liver venous deprivation and the radio-embolization are the most recent promising techniques. Despite even more precise tools to calculate the relationship among volume and function, such as scintigraphy with 99mTc-mebrofenin (HBS), no consensus is still available to define which of the above mentioned augmentation strategy is more adequate in terms of kind of surgery, complexity of the pathology and quality of liver parenchyma. The aim of this article is to analyse these different strategies to achieve sufficient FRL.
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Affiliation(s)
- Riccardo Memeo
- Division of Hepato-Pancreato-Biliary Surgery, Department of Surgery, "F. Miulli" General Hospital, Acquaviva delle Fonti, Bari, Italy
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- Emmanuel Deshayes
- Department of Nuclear Medicine, Institute du Cancer de Montpellier (ICM), Montpellier, France.,INSERM U1194, Montpellier Cancer Research Institute, Montpellier University, Montpellier, France
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- Silvio Nadalin
- Department of General, Visceral and Transplant Surgery, University Hospital Tübingen, Germany
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- Astrid Herrero
- Department of Surgery, Division of HBP Surgery and Liver Transplantation, St-Eloi University Hospital, Montpellier, France
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- Boris Guiu
- INSERM U1194, Montpellier Cancer Research Institute, Montpellier University, Montpellier, France.,Department of Radiology, St-Eloi University Hospital, Montpellier, France
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- Fabrizio Panaro
- Department of Surgery, Division of HBP Surgery and Liver Transplantation, St-Eloi University Hospital, Montpellier, France
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29
Jo HS, Han JH, Choi YY, Seok JI, Yoon YI, Kim DS. The beneficial impacts of splanchnic vasoactive agents on hepatic functional recovery in massive hepatectomy porcine model.
Hepatobiliary Surg Nutr 2021;
10:325-336. [PMID:
34159160 DOI:
10.21037/hbsn.2019.11.31]
[Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Background
Excessive portal pressure after massive hepatectomy can cause hepatic sinusoidal injury and have deleterious impacts on hepatic functional recovery, contributing to developing post-hepatectomy liver failure. This study aimed to assess the effects of splanchnic vasoactive agents on hepatic functional recovery and regeneration while clarifying the underlying mechanism, using a 70% hepatectomy porcine model.
Methods
Eighteen pigs undergoing 70% hepatectomy were involved in this study and divided into three groups: control (n=6), terlipressin (n=6), and octreotide (n=6). Terlipressin (0.5 mg) and octreotide (0.2 mg) were administered 3 times a day for each group with the first dose starting just before surgery until the 7th postoperative day, at which time the surviving pigs were sacrificed. During the period, portal pressure, liver weight, biochemical analysis, histological injury score, and molecular markers were evaluated and compared between groups.
Results
The 7-day survival rates in the octreotide, terlipressin, and control groups were 100%, 83.3%, and 66.7%, respectively. The portal pressures decreased in both terlipressin and octreotide groups than the control group at 30 minutes, 1 hour and 6 hours after hepatectomy. The amount of regeneration measured by liver weight to body weight ratio at the time of sacrifice in the terlipressin group was smaller than that in the control group (117% vs. 129%, P=0.03). Serum aspartate aminotransferase (AST) and total bilirubin levels at 1 and 6 hours after hepatectomy and prothrombin time/international normalized ratio (PT/INR) at 6 hours after hepatectomy were significantly improved in the terlipressin and octreotide groups compared to the control group. Serum endothelin-1 (ET-1) was significantly lower in the terlipressin group than that in the control group 6 hours after hepatectomy (P<0.01). The histological injury score in the control group was significantly higher than that in the terlipressin group on the 7th postoperative day (P<0.01).
Conclusions
Splanchnic vasoactive agents, such as terlipressin and octreotide, could effectively decrease portal pressure and attenuate liver injury after massive hepatectomy.
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Affiliation(s)
- Hye-Sung Jo
- Division of HBP Surgery and Liver Transplantation, Department of Surgery, Korea University College of Medicine, Seoul, Republic of Korea
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- Jae Hyun Han
- Department of Surgery, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
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- Yoon Young Choi
- Department of Biomedical Science, Korea University College of Medicine Graduate School, Seoul, Republic of Korea
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- Jin-I Seok
- Department of Biomedical Science, Korea University College of Medicine Graduate School, Seoul, Republic of Korea
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- Young-In Yoon
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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- Dong-Sik Kim
- Division of HBP Surgery and Liver Transplantation, Department of Surgery, Korea University College of Medicine, Seoul, Republic of Korea
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30
Kanou S, Miyashita T, Yamamoto Y, Takada S, Nakura M, Okazaki M, Ohbatake Y, Nakanuma S, Makino I, Tajima H, Takamura H, Fushida S, Ohta T. Prophylactic Effect of Recombinant Human Soluble Thrombomodulin for Hepatic Sinusoidal Obstruction Syndrome Model Mice.
In Vivo 2021;
34:1037-1045. [PMID:
32354890 DOI:
10.21873/invivo.11873]
[Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2019] [Revised: 03/17/2020] [Accepted: 03/18/2020] [Indexed: 02/08/2023]
Abstract
AIM
The present study aimed to examine the effects of prophylactic administration of recombinant human soluble thrombomodulin (rTM) for the prevention of sinusoidal obstruction syndrome (SOS).
MATERIALS AND METHODS
Crl:CD1 mice were allocated to the rTM, placebo, and control groups. The rTM group received an intraperitoneal administration of rTM, with intraperitoneal administration of monocrotaline (MCT) 1 h later. The placebo group received PBS instead of rTM, and the control group received PBS instead of rTM and MCT. Mice were sacrificed 48 h after MCT administration, and blood and liver tissues were evaluated. Immunostaining was performed using anti-CD42b and anti-SE-1 antibodies, and AZAN staining. Levels of plasminogen activator inhibitor (PAI-1) and endothelial nitric oxide synthase (eNOS) in whole liver tissues were estimated using RT-PCR.
RESULTS
Hematoxylin-eosin staining showed that SOS-related findings were markedly attenuated in the rTM group compared to the placebo group. CD42b immunostaining showed the presence of extravasated platelet activation (EPA) in the Disse space in the placebo group, but this was less noticeable in the rTM group. PAI-1 levels were significantly lower in the rTM group than in the placebo group in RT-PCR. However, eNOS levels were significantly higher in the rTM group than in the placebo group.
CONCLUSION
Administration of rTM may prevent SOS by protecting sinusoidal endothelial cells.
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Affiliation(s)
- Shunsuke Kanou
- Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan
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- Tomoharu Miyashita
- Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan
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- Yasuhiko Yamamoto
- Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan
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- Satoshi Takada
- Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan
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- Makoto Nakura
- Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan
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- Mitsuyoshi Okazaki
- Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan
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- Yoshinao Ohbatake
- Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan
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- Shinichi Nakanuma
- Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan
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- Isamu Makino
- Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan
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- Hidehiro Tajima
- Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan
| |
- Hiroyuki Takamura
- Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan
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- Sachio Fushida
- Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan
| |
- Tetsuo Ohta
- Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan
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31
Gao C, Peng J. All routes lead to Rome: multifaceted origin of hepatocytes during liver regeneration.
CELL REGENERATION 2021;
10:2. [PMID:
33403526 PMCID:
PMC7785766 DOI:
10.1186/s13619-020-00063-3]
[Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/21/2020] [Accepted: 09/09/2020] [Indexed: 12/19/2022]
Abstract
Liver is the largest internal organ that serves as the key site for various metabolic activities and maintenance of homeostasis. Liver diseases are great threats to human health. The capability of liver to regain its mass after partial hepatectomy has widely been applied in treating liver diseases either by removing the damaged part of a diseased liver in a patient or transplanting a part of healthy liver into a patient. Vast efforts have been made to study the biology of liver regeneration in different liver-damage models. Regarding the sources of hepatocytes during liver regeneration, convincing evidences have demonstrated that different liver-damage models mobilized different subtype hepatocytes in contributing to liver regeneration. Under extreme hepatocyte ablation, biliary epithelial cells can undergo dedifferentiation to liver progenitor cells (LPCs) and then LPCs differentiate to produce hepatocytes. Here we will focus on summarizing the progresses made in identifying cell types contributing to producing new hepatocytes during liver regeneration in mice and zebrafish.
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Affiliation(s)
- Ce Gao
- MOE Key Laboratory for Molecular Animal Nutrition, College of Animal Sciences, Zhejiang University, Hangzhou, 310058, China
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- Jinrong Peng
- MOE Key Laboratory for Molecular Animal Nutrition, College of Animal Sciences, Zhejiang University, Hangzhou, 310058, China.
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32
Yagi S, Hirata M, Miyachi Y, Uemoto S. Liver Regeneration after Hepatectomy and Partial Liver Transplantation.
Int J Mol Sci 2020;
21:ijms21218414. [PMID:
33182515 PMCID:
PMC7665117 DOI:
10.3390/ijms21218414]
[Citation(s) in RCA: 112] [Impact Index Per Article: 22.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Revised: 11/04/2020] [Accepted: 11/05/2020] [Indexed: 02/07/2023] Open
Abstract
The liver is a unique organ with an abundant regenerative capacity. Therefore, partial hepatectomy (PHx) or partial liver transplantation (PLTx) can be safely performed. Liver regeneration involves a complex network of numerous hepatotropic factors, cytokines, pathways, and transcriptional factors. Compared with liver regeneration after a viral- or drug-induced liver injury, that of post-PHx or -PLTx has several distinct features, such as hemodynamic changes in portal venous flow or pressure, tissue ischemia/hypoxia, and hemostasis/platelet activation. Although some of these changes also occur during liver regeneration after a viral- or drug-induced liver injury, they are more abrupt and drastic following PHx or PLTx, and can thus be the main trigger and driving force of liver regeneration. In this review, we first provide an overview of the molecular biology of liver regeneration post-PHx and -PLTx. Subsequently, we summarize some clinical conditions that negatively, or sometimes positively, interfere with liver regeneration after PHx or PLTx, such as marginal livers including aged or fatty liver and the influence of immunosuppression.
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33
Tsomaia K, Patarashvili L, Karumidze N, Bebiashvili I, Azmaipharashvili E, Modebadze I, Dzidziguri D, Sareli M, Gusev S, Kordzaia D. Liver structural transformation after partial hepatectomy and repeated partial hepatectomy in rats: A renewed view on liver regeneration.
World J Gastroenterol 2020;
26:3899-3916. [PMID:
32774065 PMCID:
PMC7385567 DOI:
10.3748/wjg.v26.i27.3899]
[Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Revised: 05/12/2020] [Accepted: 06/23/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND
The phenomenon of liver regeneration after partial hepatectomy (PH) is still a subject of considerable interest due to the increasing frequency of half liver transplantation on the one hand, and on the other hand, new surgical approaches which allow removal of massive space-occupying hepatic tumors, which earlier was considered as inoperable. Interestingly, the mechanisms of liver regeneration are extensively studied after PH but less attention is paid to the architectonics of the regenerated organ. Because of this, the question "How does the structure of regenerated liver differ from normal, regular liver?" has not been fully answered yet. Furthermore, almost without any attention is left the liver's structural transformation after repeated hepatectomy (of the re-regenereted liver).
AIM
To compare the architectonics of the lobules and circulatory bed of normal, re-generated and re-regenerated livers.
METHODS
The livers of 40 adult, male, albino Wistar rats were studied. 14 rats were subjected to PH - the 1st study group (SG1); 10 rats underwent repeated PH - the 2nd study group (SG2); 16 rats were subjected to sham operation - control group (CG); The livers were studied after 9 months from PH, and after 6 months from repeated PH. Cytological (Schiff reaction for the determination of DNA concen-tration), histological (H&E, Masson trichrome, CK8 Immunohistochemical marker, transparent slides after Indian Ink injection, ), morphometrical (hepatocytes areas, perimeters and ploidy) and Electron Microscopical (Scanning Electron Microscopy of corrosion casts) methods were used.
RESULTS
In the SG1 and SG2, the area of hepatocytes and their perimeter are increased compared to the CG (P < 0.05). However, the areas and perimeters of the hepatocytes of the SG1 and SG2 groups reveal a lesser difference. In regenerated (SG1) and re-regenerated (SG2) livers, the hepatocytes form the remodeled lobules, which size (300-1200 µm) exceeds the sizes of the lobules from CG (300-600 µm). The remodeled lobules (especially the "mega-lobules" with the sizes 1000-1200 µm) contain the transformed meshworks of the sinusoids, the part of which is dilated asymmetrically. This meshwork might have originated from the several portal venules (interlobular and/or inlet). The boundaries between the adjacent lobules (including mega-lobules) are widened and filled by connective tissue fibers, which gives the liver parenchyma a nodular look. In SG2 the unevenness of sinusoid diameters, as well as the boundaries between the lobules (including the mega-lobules) are more vividly expressed in comparison with SG1. The liver tissue of both SG1 and SG2 is featured by the slightly expressed ductular reaction.
CONCLUSION
Regenerated and re-regenerated livers in comparison with normal liver contain hypertrophied hepatocytes with increased ploidy which together with transformed sinusoidal and biliary meshworks form the remodeled lobulli.
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Affiliation(s)
- Keti Tsomaia
- Faculty of Medicine, Ivane Javakhishvili Tbilisi State University, Tbilisi 0159, Georgia
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- Leila Patarashvili
- Faculty of Medicine, Ivane Javakhishvili Tbilisi State University, Tbilisi 0159, Georgia
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- Nino Karumidze
- Faculty of Medicine, Ivane Javakhishvili Tbilisi State University, Tbilisi 0159, Georgia
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- Irakli Bebiashvili
- Faculty of Medicine, Ivane Javakhishvili Tbilisi State University, Tbilisi 0159, Georgia
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- Elza Azmaipharashvili
- Faculty of Medicine, Ivane Javakhishvili Tbilisi State University, Tbilisi 0159, Georgia
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- Irina Modebadze
- Faculty of Exact and Natural Sciences, Ivane Javakhishvili Tbilisi State University, Tbilisi 0179, Georgia
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- Diana Dzidziguri
- Faculty of Exact and Natural Sciences, Ivane Javakhishvili Tbilisi State University, Tbilisi 0179, Georgia
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- Marom Sareli
- Department of Surgical Oncology (Surgery C), Chaim Sheba Medical Center at HaShomer, Tel Aviv 52621, Israel
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- Sergey Gusev
- Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow 119435, Russia
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- Dimitri Kordzaia
- Faculty of Medicine, Ivane Javakhishvili Tbilisi State University, Tbilisi 0159, Georgia
- Clinical Anatomy and Operative Surgery, Ivane Javakhishvili Tbilisi State University, Tbilisi 0159, Georgia
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34
Elchaninov AV, Fatkhudinov TK, Vishnyakova PA, Nikitina MP, Lokhonina AV, Makarov AV, Arutyunyan IV, Kananykhina EY, Poltavets AS, Butov KR, Baranov II, Goldshtein DV, Bolshakova GB, Glinkina VV, Sukhikh GT. Molecular mechanisms of splenectomy-induced hepatocyte proliferation.
PLoS One 2020;
15:e0233767. [PMID:
32531779 PMCID:
PMC7292681 DOI:
10.1371/journal.pone.0233767]
[Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Accepted: 05/12/2020] [Indexed: 02/07/2023] Open
Abstract
Functional and anatomical connection between the liver and the spleen is most clearly manifested in various pathological conditions of the liver (cirrhosis, hepatitis). The mechanisms of the interaction between the two organs are still poorly understood, as there have been practically no studies on the influence exerted by the spleen on the normal liver. Mature male Sprague-Dawley rats of 250-260 g body weight, 3 months old, were splenectomized. The highest numbers of Ki67+ hepatocytes in the liver of splenectomized rats were observed at 24 h after the surgery, simultaneously with the highest index of Ki67-positive hepatocytes. After surgical removal of the spleen, expression of certain genes in the liver tissues increased. A number of genes were upregulated in the liver at a single time point of 24 h, including Ccne1, Egf, Tnfa, Il6, Hgf, Met, Tgfb1r2 and Nos2. The expression of Ccnd1, Tgfb1, Tgfb1r1 and Il10 in the liver was upregulated over the course of 3 days after splenectomy. Monitoring of the liver macrophage populations in splenectomized animals revealed a statistically significant increase in the proportion of CD68-positive cells in the liver (as compared with sham-operated controls) detectable at 24 h and 48 h after the surgery. The difference in the liver content of CD68-positive cells between splenectomized and sham-operated animals evened out by day 3 after the surgery. No alterations in the liver content of CD163-positive cells were observed in the experiments. A decrease in the proportion of CD206-positive liver macrophages was observed at 48 h after splenectomy. The splenectomy-induced hepatocyte proliferation is described by us for the first time. Mechanistically, the effect is apparently induced by the removal of spleen as a major source of Tgfb1 (hepatocyte growth inhibitor) and subsequently supported by activation of proliferation factor-encoding genes in the liver.
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Affiliation(s)
- Andrey V. Elchaninov
- Laboratory of Regenerative Medicine, National Medical Research Center for Obstetrics, Gynecology and Perinatology Named After Academician V.I.Kulakov of Ministry of Healthcare of Russian Federation, Moscow, Russian Federation
- Histology Department, Peoples Friendship University of Russia (RUDN University), Moscow, Russian Federation
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- Timur Kh. Fatkhudinov
- Histology Department, Peoples Friendship University of Russia (RUDN University), Moscow, Russian Federation
- Laboratory of Growth and Development, Research Institute of Human Morphology, Moscow, Russian Federation
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- Polina A. Vishnyakova
- Laboratory of Regenerative Medicine, National Medical Research Center for Obstetrics, Gynecology and Perinatology Named After Academician V.I.Kulakov of Ministry of Healthcare of Russian Federation, Moscow, Russian Federation
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- Maria P. Nikitina
- Laboratory of Growth and Development, Research Institute of Human Morphology, Moscow, Russian Federation
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- Anastasiya V. Lokhonina
- Laboratory of Regenerative Medicine, National Medical Research Center for Obstetrics, Gynecology and Perinatology Named After Academician V.I.Kulakov of Ministry of Healthcare of Russian Federation, Moscow, Russian Federation
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- Andrey V. Makarov
- Laboratory of Regenerative Medicine, National Medical Research Center for Obstetrics, Gynecology and Perinatology Named After Academician V.I.Kulakov of Ministry of Healthcare of Russian Federation, Moscow, Russian Federation
- Histology Department, Pirogov Russian National Research Medical University, Ministry of Healthcare of the Russian Federation, Moscow, Russian Federation
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- Irina V. Arutyunyan
- Laboratory of Regenerative Medicine, National Medical Research Center for Obstetrics, Gynecology and Perinatology Named After Academician V.I.Kulakov of Ministry of Healthcare of Russian Federation, Moscow, Russian Federation
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- Evgeniya Y. Kananykhina
- Laboratory of Growth and Development, Research Institute of Human Morphology, Moscow, Russian Federation
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- Anastasiya S. Poltavets
- Laboratory of Regenerative Medicine, National Medical Research Center for Obstetrics, Gynecology and Perinatology Named After Academician V.I.Kulakov of Ministry of Healthcare of Russian Federation, Moscow, Russian Federation
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- Kirill R. Butov
- Histology Department, Pirogov Russian National Research Medical University, Ministry of Healthcare of the Russian Federation, Moscow, Russian Federation
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- Igor I. Baranov
- Laboratory of Regenerative Medicine, National Medical Research Center for Obstetrics, Gynecology and Perinatology Named After Academician V.I.Kulakov of Ministry of Healthcare of Russian Federation, Moscow, Russian Federation
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- Dmitry V. Goldshtein
- Laboratory of Stem Cells Genetics, Research Center of Medical Genetics, Moscow, Russian Federation
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- Galina B. Bolshakova
- Laboratory of Growth and Development, Research Institute of Human Morphology, Moscow, Russian Federation
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- Valeria V. Glinkina
- Histology Department, Pirogov Russian National Research Medical University, Ministry of Healthcare of the Russian Federation, Moscow, Russian Federation
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- Gennady T. Sukhikh
- Laboratory of Regenerative Medicine, National Medical Research Center for Obstetrics, Gynecology and Perinatology Named After Academician V.I.Kulakov of Ministry of Healthcare of Russian Federation, Moscow, Russian Federation
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35
Ishikawa T, Sasaki R, Nishimura T, Iwamoto T, Takami T, Yamasaki T, Sakaida I. Improved Hepatic Reserve and Fibrosis in a Case of "Portal-Systemic Liver Failure" by Portosystemic Shunt Occlusion.
AMERICAN JOURNAL OF CASE REPORTS 2020;
21:e921236. [PMID:
32063601 PMCID:
PMC7038637 DOI:
10.12659/ajcr.921236]
[Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Patient: Female, 67-year-old
Final Diagnosis: Portal-systemic liver failure
Symptoms: None (second opinion)
Medication: None
Clinical Procedure: Balloon-occluded retrograde transvenous obliteration (BRTO) Specialty: Radiology
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Affiliation(s)
- Tsuyoshi Ishikawa
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan
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- Ryo Sasaki
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan
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- Tatsuro Nishimura
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan
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- Takuya Iwamoto
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan
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- Taro Takami
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan
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- Takahiro Yamasaki
- Department of Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan
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- Isao Sakaida
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan
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36
Li H, Ge X, Pan K, Sui M, Cai H, Cui C, Li C, Lu S. The Predictive Role of Tenascin-C and Cellular Communication Network Factor 3 (CCN3) in Post Hepatectomy Liver Failure in a Rat Model and 50 Patients Following Partial Hepatectomy.
Med Sci Monit 2019;
25:6755-6766. [PMID:
31494663 PMCID:
PMC6752097 DOI:
10.12659/msm.917331]
[Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Background
Matricellular proteins of the extracellular matrix (ECM) include tenascin-C (TNC) and cellular communication network factor 3 (CCN3). This study aimed to investigate the role of TNC and CCN3 as prognostic factors for post hepatectomy liver failure (PHLF) in a rat model of partial hepatectomy and 50 patients following partial hepatectomy.
Material/Methods
Sprague-Dawley rats underwent 85% (n=53) or 90% hepatectomy (n=53) in the partial hepatectomy (PHx) model. TNC and CCN3 mRNA expression in residual liver tissue was evaluated using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and enzyme-linked immunoassay (ELISA) determined the serum levels of TNC and CCN3. In 50 patients who underwent partial hepatectomy, TNC and CCN3 serum levels were measured on postoperative day 1 and day 3.
Results
In the rat partial hepatectomy model, mRNA and serum levels of TNC and CCN3 were significantly increased within the first 24 h, and were higher in the 90% PHx group compared with the 85% PHx group. Fifty patients who underwent partial hepatectomy, included patients with PHLF (n=12) and patients without PHLF (n=38). Multivariate analysis confirmed that serum levels on postoperative day 3 TNChigh+CCN3high was a significant predictor of PHLF, which was associated with more than twice the risk of severe morbidity when compared with the low-risk patients (80% vs. 30%) and a significantly longer hospital stay (17 days vs. 8 days).
Conclusions
Further studies are needed to evaluate the potential role of the matricellular proteins, TNC and CCN3 as early clinical predictors for PHLF.
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Affiliation(s)
- Hao Li
- Department of Hepatobiliary Surgery, The First Medical Center, Chinese People's Liberation Army (PLA) General Hospital, Chinese PLA Medical School, Beijing, China (mainland)
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- Xinlan Ge
- Institute of Hepatobiliary Surgery, The First Medical Center, Chinese People's Liberation Army (PLA) General Hospital, Chinese PLA Medical School, Beijing, China (mainland)
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- Ke Pan
- Institute of Hepatobiliary Surgery, The First Medical Center, Chinese People's Liberation Army (PLA) General Hospital, Chinese PLA Medical School, Beijing, China (mainland)
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- Minghao Sui
- Department of Hepatobiliary Surgery, The First Medical Center, Chinese People's Liberation Army (PLA) General Hospital, Chinese PLA Medical School, Beijing, China (mainland)
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- Huayong Cai
- Department of Hepatobiliary Surgery, The First Medical Center, Chinese People's Liberation Army (PLA) General Hospital, Chinese PLA Medical School, Beijing, China (mainland)
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- Chao Cui
- Department of Hepatobiliary Surgery, The First Medical Center, Chinese People's Liberation Army (PLA) General Hospital, Chinese PLA Medical School, Beijing, China (mainland)
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- Chonghui Li
- Institute of Hepatobiliary Surgery, The First Medical Center, Chinese People's Liberation Army (PLA) General Hospital, Chinese PLA Medical School, Beijing, China (mainland)
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- Shichun Lu
- Department of Hepatobiliary Surgery, The First Medical Center, Chinese People's Liberation Army (PLA) General Hospital, Chinese PLA Medical School, Beijing, China (mainland)
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37
Abstract
Posthepatectomy liver failure (PHLF) still represents a severe complication after major liver resection associated with a high mortality. In addition to an insufficient residual liver volume various factors play an important role in the pathophysiology of PHLF. These include the quality of the parenchyma, liver function, perfusion, i.e. maintenance of adequate inflow and outflow, as well as the condition of the patient and comorbidities. While the liver volume is relatively easy to evaluate using modern imaging techniques, the evaluation of liver function and liver quality require a differentiated approach. Both factors can be influenced by the constitutional status of the patient, medical history and previous treatment and must be given sufficient consideration in the risk evaluation. An adequate perfusion, e.g. portal and arterial circulation and adequate outflow by at least one hepatic vein as well an adequate biliary drainage should be always guaranteed in order to allow regeneration of the residual liver tissue. Only the understanding of all these aspects will support the surgeon in a correct and safe evaluation of the resectability. Additionally, the liver surgeon should be aware of all available perioperative and postoperative options to treat and to prevent PHLF. In this review article the most important questions regarding the risk factors related to PHLF are presented and the potential therapeutic and prophylactic management is described. The main goal is to ensure functional operability of the patient if oncological resectability is possible. In other words: in the case of correct oncological indication, the liver surgeon should be able to resect what is resectable or, alternatively, make resectable what primarily was not resectable.
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Affiliation(s)
- I Capobianco
- Universitätsklinik für Allgemeine, Viszeral- und Transplantationschirurgie Tübingen, Hoppe-Seylerstraße 3, 72076, Tübingen, Deutschland
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- J Strohäker
- Universitätsklinik für Allgemeine, Viszeral- und Transplantationschirurgie Tübingen, Hoppe-Seylerstraße 3, 72076, Tübingen, Deutschland
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- A Della Penna
- Universitätsklinik für Allgemeine, Viszeral- und Transplantationschirurgie Tübingen, Hoppe-Seylerstraße 3, 72076, Tübingen, Deutschland
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- S Nadalin
- Universitätsklinik für Allgemeine, Viszeral- und Transplantationschirurgie Tübingen, Hoppe-Seylerstraße 3, 72076, Tübingen, Deutschland
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- A Königsrainer
- Universitätsklinik für Allgemeine, Viszeral- und Transplantationschirurgie Tübingen, Hoppe-Seylerstraße 3, 72076, Tübingen, Deutschland.
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38
Iwasaki J, Afify M, Bleilevens C, Klinge U, Weiskirchen R, Steitz J, Vogt M, Yagi S, Nagai K, Uemoto S, Tolba RH. The Impact of a Nitric Oxide Synthase Inhibitor (L-NAME) on Ischemia⁻Reperfusion Injury of Cholestatic Livers by Pringle Maneuver and Liver Resection after Bile Duct Ligation in Rats.
Int J Mol Sci 2019;
20:ijms20092114. [PMID:
31035686 PMCID:
PMC6539833 DOI:
10.3390/ijms20092114]
[Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2019] [Revised: 04/19/2019] [Accepted: 04/24/2019] [Indexed: 02/07/2023] Open
Abstract
The Pringle maneuver (PM) has been widely used to control blood loss during liver resection. However, hepatic inflow occlusion can also result in hepatic ischemia–reperfusion injury (IRI), especially in patients with a cholestatic, fibrotic, or cirrhotic liver. Here we investigate a nitric oxide synthase (NOS) inhibitor N-Nitroarginine methyl ester (L-NAME) on IRI after the PM and partial hepatectomy of cholestatic livers induced by bile duct ligation (BDL) in rats. Control group (non-BDL/no treatment), BDL + T group (BDL/L-NAME treatment) and BDL group (BDL/no treatment) were analyzed. Cholestasis was induced by BDL in the L-NAME and BDL group and a 50% partial hepatectomy with PM was performed. L-NAME was injected before PM in the BDL + T group. Hepatocellular damage, portal venous flow, microcirculation, endothelial lining, and eNOS, iNOS, interleukin (IL)-6, and transforming growth factor-β (TGF-β) were evaluated. Microcirculation of the liver in the BDL + T group tended to be higher. Liver damage and apoptotic index were significantly lower and Ki-67 labeling index was higher in the BDL + T group while iNOS and TGF-β expression was decreased. This was corroborated by a better preserved endothelial lining. L-NAME attenuated IRI following PM and improved proliferation/regeneration of cholestatic livers. These positive effects were considered as the result of improved hepatic microcirculation, prevention of iNOS formation, and TGF-β mRNA upregulation.
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Affiliation(s)
- Junji Iwasaki
- Institute for Laboratory Animal Science and Experimental Surgery, RWTH-Aachen University, Medical Faculty, 52074 Aachen, Germany.
- Two Photon Imaging Facility of the Interdisciplinary Center for Clinical Research (IZKF), RWTH-Aachen University, Medical Faculty, 52074 Aachen, Germany.
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- Mamdouh Afify
- Institute for Laboratory Animal Science and Experimental Surgery, RWTH-Aachen University, Medical Faculty, 52074 Aachen, Germany.
- Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza Square 12211, Egypt.
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- Christian Bleilevens
- Department of Anesthesiology, RWTH-Aachen University, Medical Faculty, 52074 Aachen, Germany.
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- Uwe Klinge
- Department of General, Visceral and Transplantation Surgery, RWTH-Aachen University, Medical Faculty, 52074 Aachen, Germany.
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- Ralf Weiskirchen
- Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry, RWTH-Aachen University, Medical Faculty, 52074 Aachen, Germany.
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- Julia Steitz
- Institute for Laboratory Animal Science and Experimental Surgery, RWTH-Aachen University, Medical Faculty, 52074 Aachen, Germany.
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- Michael Vogt
- Institute for Laboratory Animal Science and Experimental Surgery, RWTH-Aachen University, Medical Faculty, 52074 Aachen, Germany.
- Two Photon Imaging Facility of the Interdisciplinary Center for Clinical Research (IZKF), RWTH-Aachen University, Medical Faculty, 52074 Aachen, Germany.
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- Shintaro Yagi
- Division of Hepatobiliary Pancreatic and Transplant Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
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- Kazuyuki Nagai
- Division of Hepatobiliary Pancreatic and Transplant Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
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- Shinji Uemoto
- Division of Hepatobiliary Pancreatic and Transplant Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
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- Rene H Tolba
- Institute for Laboratory Animal Science and Experimental Surgery, RWTH-Aachen University, Medical Faculty, 52074 Aachen, Germany.
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39
Kovács T, Déri M, Fülöp A, Pálházy T, Háfra E, Sirok D, Kiss ÁF, Lotz G, Szijártó A, Monostory K. Isoform-Dependent Changes in Cytochrome P450-Mediated Drug Metabolism after Portal Vein Ligation in the Rat.
Eur Surg Res 2018;
59:301-319. [PMID:
30419560 DOI:
10.1159/000493923]
[Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2018] [Accepted: 09/19/2018] [Indexed: 11/19/2022]
Abstract
BACKGROUND
Surgical removal of complicated liver tumors may be realized in two stages via selective portal vein ligation, inducing the atrophy of portally ligated lobes and the compensatory hypertrophy of nonligated liver lobes. Unlike morphological changes, functional aspects such as hepatic cytochrome P450 (CYP)-mediated drug metabolism remain vaguely understood, despite its critical role in both drug biotransformation and hepatic functional analysis. Our goal was the multilevel characterization of hepatic CYP-mediated drug metabolism after portal vein ligation in the rat.
METHODS
Male Wistar rats (n = 24, 210-230 g) were analyzed either untreated (controls; n = 4) or 24/48/72/168/336 h (n = 4 each) following portal vein ligation affecting approximately 80% of the liver parenchyma. Besides the weights of ligated and nonligated lobes, pentobarbital (30 mg/kg)-induced sleeping time, CYP1A(2), CYP 2B(1/2), CYP2C(6/11/13), CYP3A(1) enzyme activities, and corresponding isoform mRNA expressions, as well as CYP3A1 protein expression were determined by in vivo sleeping test, CYP isoform-selective assays, polymerase chain reaction, and immunohistochemistry, respectively.
RESULTS
Portal vein ligation triggered atrophy in ligated lobes and hypertrophy nonligated lobes. Sleeping time was transiently elevated (p = 0.0451). After an initial rise, CYP1A, CYP2B, and CYP3A enzyme activities dropped until 72 h, followed by a potent increase only in the nonligated lobes, paralleled by an early (24-48 h) transcriptional activation only in nonligated lobes. CYP2C enzyme activities and mRNA levels were bilaterally rapidly decreased, showing a late reconvergence only in nonligated lobes. CYP3A1 immunohistochemistry indicated substantial differences in positivity in the early period.
CONCLUSIONS
Beyond the atrophy-hypertrophy complex, portal vein ligation generated a transient suppression of global and regional drug metabolism, re-established by an adaptive, CYP isoform-dependent transcriptional response of the nonligated lobes.
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Affiliation(s)
- Tibor Kovács
- Hepato-Pancreatico-Biliary Surgery Research Center Hungary, 1st Department of Surgery, Semmelweis University, Budapest, Hungary
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- Máté Déri
- Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary
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- András Fülöp
- Hepato-Pancreatico-Biliary Surgery Research Center Hungary, 1st Department of Surgery, Semmelweis University, Budapest, Hungary
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- Tímea Pálházy
- Hepato-Pancreatico-Biliary Surgery Research Center Hungary, 1st Department of Surgery, Semmelweis University, Budapest, Hungary
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- Edit Háfra
- Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary
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- Dávid Sirok
- Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary
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- Ádám Ferenc Kiss
- Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary
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- Gábor Lotz
- 2nd Department of Pathology, Semmelweis University, Budapest, Hungary
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- Attila Szijártó
- Hepato-Pancreatico-Biliary Surgery Research Center Hungary, 1st Department of Surgery, Semmelweis University, Budapest, Hungary
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- Katalin Monostory
- Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary,
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40
Le Roy B, Dupré A, Gallon A, Chabrot P, Gagnière J, Buc E. Liver hypertrophy: Underlying mechanisms and promoting procedures before major hepatectomy.
J Visc Surg 2018;
155:393-401. [PMID:
30126801 DOI:
10.1016/j.jviscsurg.2018.03.005]
[Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Various procedures can promote hypertrophy of the future liver remnant (FLR) before major hepatectomy to prevent postoperative liver failure. The pathophysiological situation following portal vein embolization (PVE), hepatic artery ligation/embolization or hepatectomy remains unclear. On one hand, the main mechanisms of hepatic regeneration appear to be driven by hepatic hypoxia (involving the hepatic arterial buffer response), an increased portal blood flow inducing shear stress and the involvement of several mediators (inflammatory cytokines, vasoregulators, growth factors, eicosanoids and several hormones). On the other hand, several factors are associated with impaired liver regeneration, such as biliary obstruction, malnutrition, diabetes mellitus, male gender, age, ethanol and viral infection. All these mechanisms may explain the varying degrees of hypertrophy observed following a surgical or radiological procedure promoting hypertrophy the FLR. Radiological procedures include left and right portal vein embolization (extended or not to segment 4), sequential PVE and hepatic vein embolization (HVE), and more recently combined PVE and HVE. Surgical procedures include associated liver partition and portal vein ligation for staged hepatectomy, and more recently the combined portal embolization and arterial ligation procedure. This review aimed to clarify the pathophysiology of liver regeneration; it also describes radiological or surgical procedures employed to improve liver regeneration in terms of volumetric changes, the feasibility of the second step and the benefits and drawbacks of each procedure.
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Affiliation(s)
- B Le Roy
- Department of Digestive and Hepatobiliary Surgery, Hôpital Estaing, CHU Clermont-Ferrand, 1, place Lucie-et-Raymond-Aubrac, 63003 Clermont-Ferrand, France; UMR Auvergne UMR 6602 UCA/CNRS/SIGMA, Clermont-Ferrand Faculty of Medicine, 28, place Henri-Dunant, 63000 Clermont-Ferrand, France.
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- A Dupré
- Inserm, LabTAU UMR1032, Centre Léon-Bérard, Université Claude-Bernard Lyon 1, 69003 Lyon, France
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- A Gallon
- Department of Vascular Radiology, Hôpital Gabriel Montpied, CHU Clermont-Ferrand, place Henri-Dunant, 63000 Clermont-Ferrand, France; UMR Auvergne UMR 6602 UCA/CNRS/SIGMA, Clermont-Ferrand Faculty of Medicine, 28, place Henri-Dunant, 63000 Clermont-Ferrand, France
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- P Chabrot
- Department of Vascular Radiology, Hôpital Gabriel Montpied, CHU Clermont-Ferrand, place Henri-Dunant, 63000 Clermont-Ferrand, France; UMR Auvergne UMR 6602 UCA/CNRS/SIGMA, Clermont-Ferrand Faculty of Medicine, 28, place Henri-Dunant, 63000 Clermont-Ferrand, France
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- J Gagnière
- Department of Digestive and Hepatobiliary Surgery, Hôpital Estaing, CHU Clermont-Ferrand, 1, place Lucie-et-Raymond-Aubrac, 63003 Clermont-Ferrand, France
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- E Buc
- Department of Digestive and Hepatobiliary Surgery, Hôpital Estaing, CHU Clermont-Ferrand, 1, place Lucie-et-Raymond-Aubrac, 63003 Clermont-Ferrand, France; UMR Auvergne UMR 6602 UCA/CNRS/SIGMA, Clermont-Ferrand Faculty of Medicine, 28, place Henri-Dunant, 63000 Clermont-Ferrand, France
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41
Brige P, Hery G, Palen A, Guilbaud T, Buffat C, Moyon A, Hardwigsen J, Guedj E, Guillet B, Vidal V, Gorincour G, Chopinet S, Gregoire E. Portal vein stenosis preconditioning of living donor liver in swine: early mechanisms of liver regeneration and gain of hepatic functional mass.
Am J Physiol Gastrointest Liver Physiol 2018;
315:G117-G125. [PMID:
29470145 DOI:
10.1152/ajpgi.00390.2017]
[Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
To reduce the morbidity and mortality risk for the donor in living donor liver transplantation (LDLT), we previously identified 20% left portal vein (LPV) stenosis as an effective preconditioning method to induce cell proliferation in the contralateral lobe without downstream ipsilateral atrophy. In this study, we report the pathways involved in the first hours after preconditioning and investigate the changes in liver volume and function. Fourteen pigs were used this study. Five pigs were used to study the genetic, cellular and molecular mechanisms set up in the early hours following the establishment of our preconditioning. The remaining nine pigs were equally divided into three groups: sham-operated animals, 20% LPV stenosis, and 100% LPV stenosis. Volumetric scanning and 99 mTc-Mebrofenin hepatobiliary scintigraphy were performed before preconditioning and 14 days after to study morphological and functional changes in the liver. We demonstrated that liver regeneration triggered by 20% LPV stenosis in the contralateral lobe involves TNF-α, IL-6, and inducible nitric oxide synthase 2 by means of STAT3 and hepatocyte growth factor. We confirmed that our preconditioning was responsible for an increase in the total liver volume. Finally, we demonstrated that this volumetric gain was associated with an increase in hepatic functional capacity. NEW & NOTEWORTHY We describe a new preconditioning method for major hepatectomy that is applicable to hepatectomy for donation. We identified 20% left portal vein stenosis as effective preconditioning that is capable of inducing cell proliferation in the contralateral lobe without the downstream ipsilateral atrophy. In this study, we report the pathways involved in the first hours following preconditioning, and we confirm that 20% left portal vein stenosis is responsible for an increase in the functional capacity and total liver volume in a porcine model.
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Affiliation(s)
- Pauline Brige
- Experimental Interventional Imaging Laboratory EA-4264, European Centre for Medical Imaging Research, Aix-Marseille University , Marseille , France
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- Geraldine Hery
- Experimental Interventional Imaging Laboratory EA-4264, European Centre for Medical Imaging Research, Aix-Marseille University , Marseille , France.,Department of General Paediatric Surgery, Hôpital de la Timone, Aix-Marseille University , Marseille , France
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- Anais Palen
- Experimental Interventional Imaging Laboratory EA-4264, European Centre for Medical Imaging Research, Aix-Marseille University , Marseille , France.,Department of General Surgery and Liver Transplantation, Hôpital de la Timone, Aix-Marseille University , Marseille , France
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- Théophile Guilbaud
- Experimental Interventional Imaging Laboratory EA-4264, European Centre for Medical Imaging Research, Aix-Marseille University , Marseille , France
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- Christophe Buffat
- URMITE, CNRS UMR 6236-IRD 198, Aix-Marseille University, Marseille, France.,Laboratoire de Biochimie et de Biologie Moléculaire, Hôpital de la Conception, Marseille , France
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- Anais Moyon
- Vascular Research Center of Marseille, UMR-1076 INSERM, Aix-Marseille University , Marseille , France
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- Jean Hardwigsen
- Department of General Surgery and Liver Transplantation, Hôpital de la Timone, Aix-Marseille University , Marseille , France
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- Eric Guedj
- Nuclear Medicine, European Centre for Medical Imaging Research, Aix-Marseille University , Marseille , France
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- Benjamin Guillet
- Vascular Research Center of Marseille, UMR-1076 INSERM, Aix-Marseille University , Marseille , France
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- Vincent Vidal
- Experimental Interventional Imaging Laboratory EA-4264, European Centre for Medical Imaging Research, Aix-Marseille University , Marseille , France.,Department of Diagnostic and Interventional Imaging, Hôpital de la Timone, Aix-Marseille University , Marseille , France
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- Guillaume Gorincour
- Experimental Interventional Imaging Laboratory EA-4264, European Centre for Medical Imaging Research, Aix-Marseille University , Marseille , France.,Department of Paediatric Diagnostic and Interventional Imaging, Hôpital de la Timone, Aix-Marseille University , Marseille , France
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- Sophie Chopinet
- Department of General Surgery and Liver Transplantation, Hôpital de la Timone, Aix-Marseille University , Marseille , France
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- Emilie Gregoire
- Experimental Interventional Imaging Laboratory EA-4264, European Centre for Medical Imaging Research, Aix-Marseille University , Marseille , France.,Department of General Surgery and Liver Transplantation, Hôpital de la Timone, Aix-Marseille University , Marseille , France
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42
Chuang YH, Ou HY, Lazo MZ, Chen CL, Chen MH, Weng CC, Cheng YF. Predicting post-hepatectomy liver failure by combined volumetric, functional MR image and laboratory analysis.
Liver Int 2018;
38:868-874. [PMID:
28987012 DOI:
10.1111/liv.13608]
[Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2017] [Accepted: 10/02/2017] [Indexed: 02/13/2023]
Abstract
BACKGROUND & AIMS
To assess the efficacy of functional MR image with volumetric, liver function test and indocyanine green clearance (ICG) in identifying the patients who are at risk of post-hepatectomy liver failure (PHLF).
METHODS
We retrospectively included 115 patients undergoing gadoxetic acid-enhanced MR imaging before hepatectomy at one medical centre from January 2013 to December 2015. Contrast enhancement ratio (CER) between transitional and hepatobiliary phases (3 and 30 minutes post-contrast) was calculated. Total liver volume (TLV) and spleen volume (Sp) were measured. Post-operatively, the histological Ishak fibrosis score was collected. Potential risk factors for liver failure were analysed, and the performance was examined by receiver operating characteristic curve.
RESULTS
Post-hepatectomy liver failure (PHLF) occurred in 16 patients (13.9%). TLV/SLV, ADC value, CERHBP/TP and total liver contrast enhancement ratio (tCER) were associated with PHLF (P < .05). Between PHLF and non-PHLF groups, remnant liver volume (RLV), RLV/SLV, Sp/RLV, remnant liver contrast enhancement ratio (rCER) and Ishak fibrosis score showed statistical difference. rCER showed superiority in diagnostic performance (AUC = 0.78) with the optimal cut-off value of 1.23.
CONCLUSIONS
Gadoxetic acid-enhanced MR imaging with volumetric is a reliable method for evaluating functional liver volume and determining the risk of PHLF.
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Affiliation(s)
- Yi-Hsuan Chuang
- Liver Transplantation Program and Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
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- Hsin-You Ou
- Liver Transplantation Program and Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
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- Marirose Z Lazo
- Liver Transplantation Program and Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
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- Chao-Long Chen
- Liver Transplantation Program and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
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- Meng-Hsiang Chen
- Liver Transplantation Program and Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
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- Ching-Chun Weng
- Liver Transplantation Program and Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
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- Yu-Fan Cheng
- Liver Transplantation Program and Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
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43
Nishii K, Brodin E, Renshaw T, Weesner R, Moran E, Soker S, Sparks JL. Shear stress upregulates regeneration-related immediate early genes in liver progenitors in 3D ECM-like microenvironments.
J Cell Physiol 2017;
233:4272-4281. [PMID:
29052842 DOI:
10.1002/jcp.26246]
[Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2017] [Accepted: 10/13/2017] [Indexed: 12/16/2022]
Abstract
The role of fluid stresses in activating the hepatic stem/progenitor cell regenerative response is not well understood. This study hypothesized that immediate early genes (IEGs) with known links to liver regeneration will be upregulated in liver progenitor cells (LPCs) exposed to in vitro shear stresses on the order of those produced from elevated interstitial flow after partial hepatectomy. The objectives were: (1) to develop a shear flow chamber for application of fluid stress to LPCs in 3D culture; and (2) to determine the effects of fluid stress on IEG expression in LPCs. Two hours of shear stress exposure at ∼4 dyn/cm2 was applied to LPCs embedded individually or as 3D spheroids within a hyaluronic acid/collagen I hydrogel. Results were compared against static controls. Quantitative reverse transcriptase polymerase chain reaction was used to evaluate the effect of experimental treatments on gene expression. Twenty-nine genes were analyzed, including IEGs and other genes linked to liver regeneration. Four IEGs (CFOS, IP10, MKP1, ALB) and three other regeneration-related genes (WNT, VEGF, EpCAM) were significantly upregulated in LPCs in response to fluid mechanical stress. LPCs maintained an early to intermediate stage of differentiation in spheroid culture in the absence of the hydrogel, and addition of the gel initiated cholangiocyte differentiation programs which were abrogated by the onset of flow. Collectively the flow-upregulated genes fit the pattern of an LPC-mediated proliferative/regenerative response. These results suggest that fluid stresses are potentially important regulators of the LPC-mediated regeneration response in liver.
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Affiliation(s)
- Kenichiro Nishii
- Department of Chemical, Paper and Biomedical Engineering, Miami University, Oxford, Ohio
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- Erik Brodin
- Department of Chemical, Paper and Biomedical Engineering, Miami University, Oxford, Ohio
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- Taylor Renshaw
- Department of Chemical, Paper and Biomedical Engineering, Miami University, Oxford, Ohio
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- Rachael Weesner
- Department of Chemical, Paper and Biomedical Engineering, Miami University, Oxford, Ohio
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- Emma Moran
- Wake Forest Institute for Regenerative Medicine, Winston Salem, North Carolina
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- Shay Soker
- Wake Forest Institute for Regenerative Medicine, Winston Salem, North Carolina
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- Jessica L Sparks
- Department of Chemical, Paper and Biomedical Engineering, Miami University, Oxford, Ohio
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44
Mechanosensing in liver regeneration.
Semin Cell Dev Biol 2017;
71:153-167. [DOI:
10.1016/j.semcdb.2017.07.041]
[Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2017] [Revised: 07/25/2017] [Accepted: 07/26/2017] [Indexed: 12/13/2022]
45
Rizza S, Filomeni G. Chronicles of a reductase: Biochemistry, genetics and physio-pathological role of GSNOR.
Free Radic Biol Med 2017;
110:19-30. [PMID:
28533171 DOI:
10.1016/j.freeradbiomed.2017.05.014]
[Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2016] [Revised: 05/11/2017] [Accepted: 05/16/2017] [Indexed: 01/08/2023]
Abstract
S-nitrosylation is a major redox posttranslational modification involved in cell signaling. The steady state concentration of S-nitrosylated proteins depends on the balance between the relative ability to generate nitric oxide (NO) via NO synthase and to reduce nitrosothiols by denitrosylases. Numerous works have been published in last decades regarding the role of NO and S-nitrosylation in the regulation of protein structure and function, and in driving cellular activities in vertebrates. Notwithstanding an increasing number of observations indicates that impairment of denitrosylation equally affects cellular homeostasis, there is still no report providing comprehensive knowledge on the impact that denitrosylation has on maintaining correct physiological processes and organ activities. Among denitrosylases, S-nitrosoglutathione reductase (GSNOR) represents the prototype enzyme to disclose how denitrosylation plays a crucial role in tuning NO-bioactivity and how much it deeply impacts on cell homeostasis and human patho-physiology. In this review we attempt to illustrate the history of GSNOR discovery and provide the evidence so far reported in support of GSNOR implications in development and human disease.
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Affiliation(s)
- Salvatore Rizza
- Redox Signaling and Oxidative Stress Research Group, Cell Stress and Survival Unit, Center for Autophagy, Recycling and Disease (CARD), Danish Cancer Society Research Center, Copenhagen, Denmark
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- Giuseppe Filomeni
- Redox Signaling and Oxidative Stress Research Group, Cell Stress and Survival Unit, Center for Autophagy, Recycling and Disease (CARD), Danish Cancer Society Research Center, Copenhagen, Denmark; Department of Biology, University of Rome Tor Vergata, Rome, Italy.
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46
Yagmurdur H, Binnetoglu K, Astarci HM, Yagmurdur MC. Propofol attenuates cytokine-mediated upregulation of expression of inducible nitric oxide synthase and apoptosis during regeneration post-partial hepatectomy.
Acta Cir Bras 2017;
32:396-406. [PMID:
28591369 DOI:
10.1590/s0102-865020170050000009]
[Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2017] [Accepted: 04/19/2017] [Indexed: 01/28/2023] Open
Abstract
Purpose:
To determine the effects of propofol and ketamine anesthesia on liver regeneration in rats after partial hepatectomy (PHT).
Methods:
Male Wistar albino rats were assigned randomly to four groups of 10. Anesthesia was induced and maintained with propofol in groups 1 and 2, and with ketamine in groups 3 and 4. PHT was undertaken in groups 1 and 3. Rats in groups 2 and 4 (control groups) underwent an identical surgical procedure, but without PHT. At postoperative day-5, rats were killed. Regenerated liver was removed, weighed, and evaluated (by immunohistochemical means) for expression of inducible nitric oxide synthase (iNOS), endothelial NOS (eNOS), apoptosis protease-activating factor (APAF)-1, and proliferating cell nuclear antigen (PCNA). Also, blood samples were collected for measurement of levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6.
Results:
Between groups 2 and 4, there were no differences in tissue levels of iNOS, eNOS, and APAF-1 or plasma levels of TNF-α and IL-6. eNOS expression was similar in group 1 and group 3. Expression of iNOS and APAF-1 was mild-to-moderate in group 1, but significantly higher in group 3. Groups 1 and 3 showed an increase in PCNA expression, but expression in both groups was comparable. Plasma levels of TNF-α and IL-6 increased to a lesser degree in group 1 than in group 3.
Conclusion:
Propofol, as an anesthetic agent, may attenuate cytokine-mediated upregulation of iNOS expression and apoptosis in an animal model of liver regeneration after partial hepatectomy.
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Affiliation(s)
- Hatice Yagmurdur
- Professor, Department of Anesthesiology and Reanimation, School of Medicine, Kafkas University, Kars, Turkey. Conception and design of the study; acquisition, analysis and interpretation of data; manuscript writing; critical revision
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- Kenan Binnetoglu
- Assistant Professor, Department of General Surgery, School of Medicine, Kafkas University, Kars, Turkey. Design of the study, manuscript writing
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- Hesna Muzeyyen Astarci
- MD, Department of Pathology, Ministry of Health Ankara Research and Training Hospital, Ankara, Turkey. Acquisition, analysis and interpretation of data; manuscript writing
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- Mahmut Can Yagmurdur
- Professor, Department of General Surgery, School of Medicine, Kafkas University, Kars, Turkey. Conception of the study, analysis and interpretation of data, manuscript writing, critical revision
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47
Abstract
Liver possesses many critical functions such as synthesis, detoxification, and metabolism. It continually receives nutrient-rich blood from gut, which incidentally is also toxin-rich. That may be why liver is uniquely bestowed with a capacity to regenerate. A commonly studied procedure to understand the cellular and molecular basis of liver regeneration is that of surgical resection. Removal of two-thirds of the liver in rodents or patients instigates alterations in hepatic homeostasis, which are sensed by the deficient organ to drive the restoration process. Although the exact mechanisms that initiate regeneration are unknown, alterations in hemodynamics and metabolism have been suspected as important effectors. Key signaling pathways are activated that drive cell proliferation in various hepatic cell types through autocrine and paracrine mechanisms. Once the prehepatectomy mass is regained, the process of regeneration is adequately terminated. This review highlights recent discoveries in the cellular and molecular basis of liver regeneration.
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Affiliation(s)
- Morgan E. Preziosi
- Division of Experimental Pathology, Department of Pathology, University of Pittsburgh, School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania,Pittsburgh Liver Research Center, University of Pittsburgh, School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
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- Satdarshan P. Monga
- Division of Experimental Pathology, Department of Pathology, University of Pittsburgh, School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania,Pittsburgh Liver Research Center, University of Pittsburgh, School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania,Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh, School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
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48
佟 立, 李 子. 剪切力对肝脏切除术后肝窦内皮细胞的作用.
Shijie Huaren Xiaohua Zazhi 2017;
25:1050-1055. [DOI:
10.11569/wcjd.v25.i12.1050]
[Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
肝切除术是肝脏疾病尤其是肝脏肿瘤的重要治疗手段, 并且在肝切除术后会出现肝脏血流动力学的改变. 肝窦内皮细胞是肝窦毛细血管内一类特殊的内皮细胞, 对血流变化十分敏感. 本文就肝脏切除术后血流产生的剪切力作用于肝窦内皮细胞, 从而调节肝细胞再生和肝组织恢复的作用及机制作一综述.
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49
Le Roy B, Perrey A, Fontarensky M, Gagnière J, Abergel A, Pereira B, Lambert C, Boyer L, Pezet D, Chabrot P, Buc E. Combined Preoperative Portal and Hepatic Vein Embolization (Biembolization) to Improve Liver Regeneration Before Major Liver Resection: A Preliminary Report.
World J Surg 2017;
41:1848-1856. [DOI:
10.1007/s00268-017-4016-5]
[Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
50
Goldaracena N, Echeverri J, Selzner M. Small-for-size syndrome in live donor liver transplantation-Pathways of injury and therapeutic strategies.
Clin Transplant 2017;
31. [PMID:
27935645 DOI:
10.1111/ctr.12885]
[Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/30/2016] [Indexed: 12/14/2022]
Abstract
Due to the severe organ shortage and the increasing gap between the supply and demand for donor grafts, live donor liver transplantation (LDLT) has become an accepted and alternative technique for the expansion of the donor pool. However, donor safety and good recipient outcomes must be balanced regarding risk stratification and decision-making within this patient population. Small-for-size syndrome (SFSS) is one of the complications encountered after LDLT, thus increasing the burden of optimizing donor graft selection and effective treatments during its occurrence. A graft-to-recipient weight ratio (GRWR) <0.8 predisposes the graft to SFSS. However, other factors may induce this complication even without a graft-to-patient size mismatch. Several strategies to prevent this complication include portal vein flow and liver outflow modulation, as well as pharmacological treatment. Also, as an entity with a multifactorial etiology, outcomes vary between right-lobe, left-lobe, and posterior-lobe donation among series encountered in the literature. In this review, we analyze the pathophysiology and classification of this complication, the state-of-the-art on management of SFSS, and the outcomes regarding the best treatment strategy on this patient population.
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Affiliation(s)
- Nicolas Goldaracena
- Multi Organ Transplant Program, Department of Surgery, Toronto General Hospital, Toronto, Ontario, Canada
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- Juan Echeverri
- Multi Organ Transplant Program, Department of Surgery, Toronto General Hospital, Toronto, Ontario, Canada
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- Markus Selzner
- Multi Organ Transplant Program, Department of Surgery, Toronto General Hospital, Toronto, Ontario, Canada
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