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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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Shu W, Song Y, Lin Z, Yang M, Pan B, Su R, Yang M, Lu Z, Zheng S, Xu X, Yang Z, Wei X. Evaluation of liver regeneration after hemi-hepatectomy by combining computed tomography and post-operative liver function. Heliyon 2024; 10:e30964. [PMID: 38803961 PMCID: PMC11128876 DOI: 10.1016/j.heliyon.2024.e30964] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2023] [Revised: 05/07/2024] [Accepted: 05/08/2024] [Indexed: 05/29/2024] Open
Abstract
Background Accurate evaluation of postoperative liver regeneration is essential to prevent postoperative liver failure. Aims To analyze the predictors that affect liver regeneration after hemi-hepatectomy. Method Patients who underwent hemi-hepatectomy in Hangzhou First People's Hospital and Hangzhou Shulan Hospital from January 2016 to December 2021 were enrolled in this study. The regeneration index (RI) was calculated by the following equation: RI = [(postoperative total liver volume {TLVpost} - future liver remnant volume {FLRV}/FLRV] × 100 %. Hepatic dysfunction was defined according to the "TBilpeak>7" standard, which was interpreted as (peak) total bilirubin (TBil) >7.0 mg/dL. Good liver regeneration was defined solely when the RI surpassed the median with hepatic dysfunction. Logistic regression analyses were performed to estimate prognostic factors affecting liver regeneration. Result A total of 153 patients were enrolled, with 33 in the benign group and 120 patients in the malignant group. In the entire study population, FLRV% [OR 4.087 (1.405-11.889), P = 0.010], international normalized ratio (INR) [OR 2.763 (95%CI, 1.008-7.577), P = 0.048] and TBil [OR 2.592 (95%CI, 1.177-5.710), P = 0.018] were independent prognostic factors associated with liver regeneration. In the benign group, only the computed tomography (CT) parameter FLRV% [OR, 11.700 (95%CI, 1.265-108.200), P = 0.030] predicted regeneration. In the malignant group, parenchymal hepatic resection rate (PHRR%) [OR 0.141 (95%CI, 0.040-0.499), P = 0.002] and TBil [OR 3.384 (95%CI, 1.377-8.319), P = 0.008] were independent prognostic factors. Conclusion FLRV%, PHRR%, TBil and INR were predictive factors associated with liver regeneration.
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Affiliation(s)
- Wenzhi Shu
- Zhejiang University School of Medicine, Hangzhou First People's Hospital, Hangzhou, 310006, China
- Zhejiang University School of Medicine, Hangzhou, 310058, China
- Department of Hepatobiliary and Pancreatic Surgery, Hangzhou First People's Hospital, Hangzhou, 310006, China
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou, 310006, China
| | - Yisu Song
- Zhejiang University School of Medicine, Hangzhou First People's Hospital, Hangzhou, 310006, China
- Zhejiang University School of Medicine, Hangzhou, 310058, China
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou, 310006, China
| | - Zuyuan Lin
- Zhejiang University School of Medicine, Hangzhou First People's Hospital, Hangzhou, 310006, China
- Zhejiang University School of Medicine, Hangzhou, 310058, China
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou, 310006, China
| | - Mengfan Yang
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou, 310006, China
| | - Binhua Pan
- Zhejiang University School of Medicine, Hangzhou First People's Hospital, Hangzhou, 310006, China
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou, 310006, China
| | - Renyi Su
- Zhejiang University School of Medicine, Hangzhou First People's Hospital, Hangzhou, 310006, China
- Zhejiang University School of Medicine, Hangzhou, 310058, China
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou, 310006, China
| | - Modan Yang
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou, 310006, China
| | - Zhengyang Lu
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou, 310006, China
| | - Shusen Zheng
- Shulan (Hangzhou) Hospital, Zhejiang Shuren University School of Medicine, Hangzhou, 310022, China
| | - Xiao Xu
- Zhejiang University School of Medicine, Hangzhou, 310058, China
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou, 310006, China
| | - Zhe Yang
- Shulan (Hangzhou) Hospital, Zhejiang Shuren University School of Medicine, Hangzhou, 310022, China
| | - Xuyong Wei
- Department of Hepatobiliary and Pancreatic Surgery, Hangzhou First People's Hospital, Hangzhou, 310006, China
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou, 310006, China
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Hu Y, Wang R, An N, Li C, Wang Q, Cao Y, Li C, Liu J, Wang Y. Unveiling the power of microenvironment in liver regeneration: an in-depth overview. Front Genet 2023; 14:1332190. [PMID: 38152656 PMCID: PMC10751322 DOI: 10.3389/fgene.2023.1332190] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Accepted: 11/29/2023] [Indexed: 12/29/2023] Open
Abstract
The liver serves as a vital regulatory hub for various physiological processes, including sugar, protein, and fat metabolism, coagulation regulation, immune system maintenance, hormone inactivation, urea metabolism, and water-electrolyte acid-base balance control. These functions rely on coordinated communication among different liver cell types, particularly within the liver's fundamental hepatic lobular structure. In the early stages of liver development, diverse liver cells differentiate from stem cells in a carefully orchestrated manner. Despite its susceptibility to damage, the liver possesses a remarkable regenerative capacity, with the hepatic lobule serving as a secure environment for cell division and proliferation during liver regeneration. This regenerative process depends on a complex microenvironment, involving liver resident cells, circulating cells, secreted cytokines, extracellular matrix, and biological forces. While hepatocytes proliferate under varying injury conditions, their sources may vary. It is well-established that hepatocytes with regenerative potential are distributed throughout the hepatic lobules. However, a comprehensive spatiotemporal model of liver regeneration remains elusive, despite recent advancements in genomics, lineage tracing, and microscopic imaging. This review summarizes the spatial distribution of cell gene expression within the regenerative microenvironment and its impact on liver regeneration patterns. It offers valuable insights into understanding the complex process of liver regeneration.
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Affiliation(s)
- Yuelei Hu
- Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Jilin University, Changchun, China
- Hepato-Pancreato-Biliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
| | - Ruilin Wang
- Department of Cadre’s Wards Ultrasound Diagnostics, Ultrasound Diagnostic Center, The First Hospital of Jilin University, Jilin University, Changchun, China
| | - Ni An
- Clinical Translational Science Center, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
| | - Chen Li
- Hepato-Pancreato-Biliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
- College of Life Science and Bioengineering, Faculty of Environmental and Life Sciences, Beijing University of Technology, Beijing, China
| | - Qi Wang
- Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Jilin University, Changchun, China
- Hepato-Pancreato-Biliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
| | - Yannan Cao
- Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Jilin University, Changchun, China
- Hepato-Pancreato-Biliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
| | - Chao Li
- Hepato-Pancreato-Biliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
| | - Juan Liu
- Hepato-Pancreato-Biliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
| | - Yunfang Wang
- Hepato-Pancreato-Biliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
- Clinical Translational Science Center, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
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Bekheit M, Grundy L, Salih AK, Bucur P, Vibert E, Ghazanfar M. Post-hepatectomy liver failure: A timeline centered review. Hepatobiliary Pancreat Dis Int 2023; 22:554-569. [PMID: 36973111 DOI: 10.1016/j.hbpd.2023.03.001] [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: 04/11/2022] [Accepted: 03/10/2023] [Indexed: 03/29/2023]
Abstract
BACKGROUND Post-hepatectomy liver failure (PHLF) is a leading cause of postoperative mortality after liver surgery. Due to its significant impact, it is imperative to understand the risk stratification and preventative strategies for PHLF. The main objective of this review is to highlight the role of these strategies in a timeline centered way around curative resection. DATA SOURCES This review includes studies on both humans and animals, where they addressed PHLF. A literature search was conducted across the Cochrane Library, Embase, MEDLINE/PubMed, and Web of Knowledge electronic databases for English language studies published between July 1997 and June 2020. Studies presented in other languages were equally considered. The quality of included publications was assessed using Downs and Black's checklist. The results were presented in qualitative summaries owing to the lack of studies qualifying for quantitative analysis. RESULTS This systematic review with 245 studies, provides insight into the current prediction, prevention, diagnosis, and management options for PHLF. This review highlighted that liver volume manipulation is the most frequently studied preventive measure against PHLF in clinical practice, with modest improvement in the treatment strategies over the past decade. CONCLUSIONS Remnant liver volume manipulation is the most consistent preventive measure against PHLF.
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Affiliation(s)
- Mohamed Bekheit
- Department of Surgery, NHS Grampian, Foresterhill Health Campus, Ashgrove Road, AB252ZN Aberdeen, UK; Institute of Medical Sciences, Medical School, Foresterhill Health Campus, Ashgrove Road, AB252ZN Aberdeen, UK; Hépatica, Integrated Center of HPB Care, Elite Hospital, Agriculture Road, Alexandria, Egypt.
| | - Lisa Grundy
- Department of Surgery, NHS Grampian, Foresterhill Health Campus, Ashgrove Road, AB252ZN Aberdeen, UK
| | - Ahmed Ka Salih
- Department of Surgery, NHS Grampian, Foresterhill Health Campus, Ashgrove Road, AB252ZN Aberdeen, UK; Institute of Medical Sciences, Medical School, Foresterhill Health Campus, Ashgrove Road, AB252ZN Aberdeen, UK
| | - Petru Bucur
- Department of Surgery, University Hospital Tours, Val de la Loire 37000, France
| | - Eric Vibert
- Centre Hépatobiliaire, Paul Brousse Hospital, 12 Paul Valliant Couturier, 94804 Villejuif, France
| | - Mudassar Ghazanfar
- Department of Surgery, NHS Grampian, Foresterhill Health Campus, Ashgrove Road, AB252ZN Aberdeen, UK
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Cassese G, Han HS, Lee B, Cho JY, Lee HW, Guiu B, Panaro F, Troisi RI. Portal vein embolization failure: Current strategies and future perspectives to improve liver hypertrophy before major oncological liver resection. World J Gastrointest Oncol 2022; 14:2088-2096. [PMID: 36438704 PMCID: PMC9694272 DOI: 10.4251/wjgo.v14.i11.2088] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Revised: 10/01/2022] [Accepted: 10/31/2022] [Indexed: 11/15/2022] Open
Abstract
Portal vein embolization (PVE) is currently considered the standard of care to improve the volume of an inadequate future remnant liver (FRL) and decrease the risk of post-hepatectomy liver failure (PHLF). PHLF remains a significant limitation in performing major liver surgery and is the main cause of mortality after resection. The degree of hypertrophy obtained after PVE is variable and depends on multiple factors. Up to 20% of patients fail to undergo the planned surgery because of either an inadequate FRL growth or tumor progression after the PVE procedure (usually 6-8 wk are needed before surgery). The management of PVE failure is still debated, with a lack of consensus regarding the best clinical strategy. Different additional techniques have been proposed, such as sequential transarterial chemoembolization followed by PVE, segment 4 PVE, intra-portal administration of stem cells, dietary supplementation, and hepatic vein embolization. The aim of this review is to summarize the up-to-date strategies to overcome such difficult situations and discuss future perspectives on improving FRL hypertrophy.
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Affiliation(s)
- Gianluca Cassese
- Clinical Medicine and Surgery, Federico II University, Naples 80131, Italy
| | - Ho-Seong Han
- Department of Surgery, Seoul National University College of Medicine, Seongnam 13620, South Korea
| | - Boram Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam 13620, South Korea
| | - Jai Young Cho
- Department of Surgery, Seoul National University College of Medicine, Seongnam 13620, South Korea
| | - Hae Won Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam 13620, South Korea
| | - Boris Guiu
- Department of Medical Imaging and Interventional Radiology, St-Eloi University Hospital, Montpellier 34295, France
| | - Fabrizio Panaro
- Digestive Surgery and Transplantation, CHU de Montpellier, Montpellier 34295, France
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6
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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
| | - Ho-Seong Han
- Seoul National University College of Medicine, Department of Surgery, Seoul National University Bundang Hospital, Seoul, South Korea
| | - Abdallah Al Farai
- Department of Surgical Oncology, Sultan Qaboos Comprehensive Cancer Care and Research Center, Muscat, Oman
| | - Boris Guiu
- Department of Radiology, Montpellier University Hospital, Montpellier, France
| | - Roberto I Troisi
- Minimally Invasive and Robotic HPB Unit, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - 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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Xu L, Chen L, Zhang W. Neoadjuvant treatment strategies for hepatocellular carcinoma. World J Gastrointest Surg 2021; 13:1550-1566. [PMID: 35070063 PMCID: PMC8727178 DOI: 10.4240/wjgs.v13.i12.1550] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 06/27/2021] [Accepted: 11/30/2021] [Indexed: 02/06/2023] Open
Abstract
The incidence of hepatocellular carcinoma (HCC) remains high globally. Surgical treatment is the best treatment for improving the prognosis of patients with HCC. Neoadjuvant therapy plays a key role in preventing tumor progression and even downstaging HCC. The liver transplantation rate and resectability rate have increased for neoadjuvant therapy. Neoadjuvant therapy is effective in different stages of HCC. In this review, we summarized the definition, methods, effects, indications and contraindications of neoadjuvant therapy in HCC, which have significance for guiding treatment.
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Affiliation(s)
- Lei Xu
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Lin Chen
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Wei Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
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Del Basso C, Gaillard M, Lainas P, Zervaki S, Perlemuter G, Chagué P, Rocher L, Voican CS, Dagher I, Tranchart H. Current strategies to induce liver remnant hypertrophy before major liver resection. World J Hepatol 2021; 13:1629-1641. [PMID: 34904033 PMCID: PMC8637666 DOI: 10.4254/wjh.v13.i11.1629] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Revised: 06/08/2021] [Accepted: 10/11/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatic resection is the gold standard for patients affected by primary or metastatic liver tumors but is hampered by the risk of post-hepatectomy liver failure. Despite recent improvements, liver surgery still requires excellent clinical judgement in selecting patients for surgery and, above all, efficient pre-operative strategies to provide adequate future liver remnant. The aim of this article is to review the literature on the rational, the preliminary assessment, the advantages as well as the limits of each existing technique for preparing the liver for major hepatectomy.
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Affiliation(s)
- Celeste Del Basso
- Department of Minimally Invasive Digestive Surgery, Antoine Béclère Hospital, Clamart 92140, France
| | - Martin Gaillard
- Department of Minimally Invasive Digestive Surgery, Antoine Béclère Hospital, Clamart 92140, France
| | - Panagiotis Lainas
- Department of Minimally Invasive Digestive Surgery, Antoine Béclère Hospital, Clamart 92140, France
| | - Stella Zervaki
- Department of Minimally Invasive Digestive Surgery, Antoine Béclère Hospital, Clamart 92140, France
| | - Gabriel Perlemuter
- Department of Hepato-Gastroenterology and Nutrition, Antoine Béclère Hospital, Clamart 92140, France
| | - Pierre Chagué
- Department of Radiology, Antoine Béclère Hospital, Clamart 92140, France
| | - Laurence Rocher
- Department of Radiology, Antoine Béclère Hospital, Clamart 92140, France
| | - Cosmin Sebastian Voican
- Department of Hepato-Gastroenterology and Nutrition, Antoine Béclère Hospital, Clamart 92140, France
| | - Ibrahim Dagher
- Department of Minimally Invasive Digestive Surgery, Antoine Béclère Hospital, Clamart 92140, France
| | - Hadrien Tranchart
- Department of Minimally Invasive Digestive Surgery, Antoine Béclère Hospital, Clamart 92140, France
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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.
| | - 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
| | - 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
| | - 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
| | - 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
| | - 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
| | - 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
| | - 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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10
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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
| | | | - Emmanuel Deshayes
- Department of Nuclear Medicine, Institute du Cancer de Montpellier (ICM), Montpellier, France.,INSERM U1194, Montpellier Cancer Research Institute, Montpellier University, Montpellier, France
| | - Silvio Nadalin
- Department of General, Visceral and Transplant Surgery, University Hospital Tübingen, Germany
| | - Astrid Herrero
- Department of Surgery, Division of HBP Surgery and Liver Transplantation, St-Eloi University Hospital, Montpellier, France
| | - Boris Guiu
- INSERM U1194, Montpellier Cancer Research Institute, Montpellier University, Montpellier, France.,Department of Radiology, St-Eloi University Hospital, Montpellier, France
| | - Fabrizio Panaro
- Department of Surgery, Division of HBP Surgery and Liver Transplantation, St-Eloi University Hospital, Montpellier, France
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11
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Gaillard M, Hornez E, Lecuelle B, Lilin T, Dubart-Kupperschmitt A, Dagher I, Tranchart H. Liver Regeneration and Recanalization Time Course following Repeated Reversible Portal Vein Embolization in Swine. Eur Surg Res 2020; 61:62-71. [PMID: 33049754 DOI: 10.1159/000509713] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2020] [Accepted: 06/25/2020] [Indexed: 11/19/2022]
Abstract
INTRODUCTION Portal vein embolization (PVE) is an accepted technique to preoperatively increase the volume of the future remnant liver before major hepatectomy. A permanent material is usually preferred since its superiority to induce liver hypertrophy over absorbable material has been demonstrated. Nevertheless, the use of an absorbable material generates a reversible PVE (RPVE) capable of inducing significant liver hypertrophy. In small animal models, the possibility to proceed to a repeated RPVE (RRPVE) has shown to boost liver hypertrophy further. The aim of this preliminary study was to assess the feasibility and the tolerance of RRPVE in a large animal model, in comparison with permanent PVE (PPVE) and single RPVE. METHODS Six swine (2 per group) were assigned either to single RPVE group (using powdered gelatin sponge), RRPVE group (2 RPVEs separated by 14 days) or PPVE group (using N-butyl-cyanoacrylate). The feasibility and tolerance of the procedures were evaluated using portography, liver function tests and histological analysis. Evolution of liver volumes was assessed with volumetric imaging by computed tomography. RESULTS Embolization of portal branches corresponding to 75% of total liver volume was performed successfully in all animals. Procedures were well tolerated, inducing moderate changes in portal pressure and transient aminotransferase increase. None of the animals developed portal vein thrombosis. After RPVE, complete recanalization occurred at day 11. RRPVE showed a trend for higher hypertrophy, the non-embolized liver to total liver ratio reaching 5.2 ± 1.0% in the RPVE group, 6.8 ± 0.1% in the RRPVE group and 5.0 ± 0.3% in the PPVE group. DISCUSSION/CONCLUSION In this preliminary comparative study, RRPVE was as feasible and as well tolerated as the other procedures, and resulted in higher liver hypertrophy.
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Affiliation(s)
- Martin Gaillard
- Institut National de la Santé et de la Recherche Médicale (INSERM) U1193, Paul Brousse Hospital, Villejuif, France, .,Département Hospitalo-Universitaire Hepatinov, Paul Brousse Hospital, Villejuif, France, .,Faculté de Médecine Paris-Sud, Paris-Saclay University, Orsay, France, .,Department of Minimally Invasive Surgery, Antoine Béclère Hospital, APHP, Clamart, France,
| | - Emmanuel Hornez
- Institut National de la Santé et de la Recherche Médicale (INSERM) U1193, Paul Brousse Hospital, Villejuif, France.,Département Hospitalo-Universitaire Hepatinov, Paul Brousse Hospital, Villejuif, France.,Department of Minimally Invasive Surgery, Antoine Béclère Hospital, APHP, Clamart, France
| | - Benoit Lecuelle
- Center for Biomedical Research, Ecole Nationale Vétérinaire d'Alfort, Maisons Alfort, France
| | - Thomas Lilin
- Center for Biomedical Research, Ecole Nationale Vétérinaire d'Alfort, Maisons Alfort, France
| | - Anne Dubart-Kupperschmitt
- Institut National de la Santé et de la Recherche Médicale (INSERM) U1193, Paul Brousse Hospital, Villejuif, France.,Département Hospitalo-Universitaire Hepatinov, Paul Brousse Hospital, Villejuif, France.,Faculté de Médecine Paris-Sud, Paris-Saclay University, Orsay, France
| | - Ibrahim Dagher
- Institut National de la Santé et de la Recherche Médicale (INSERM) U1193, Paul Brousse Hospital, Villejuif, France.,Département Hospitalo-Universitaire Hepatinov, Paul Brousse Hospital, Villejuif, France.,Faculté de Médecine Paris-Sud, Paris-Saclay University, Orsay, France.,Department of Minimally Invasive Surgery, Antoine Béclère Hospital, APHP, Clamart, France
| | - Hadrien Tranchart
- Institut National de la Santé et de la Recherche Médicale (INSERM) U1193, Paul Brousse Hospital, Villejuif, France.,Département Hospitalo-Universitaire Hepatinov, Paul Brousse Hospital, Villejuif, France.,Faculté de Médecine Paris-Sud, Paris-Saclay University, Orsay, France.,Department of Minimally Invasive Surgery, Antoine Béclère Hospital, APHP, Clamart, France
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12
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Gaillard M, Tranchart H, Lainas P, Trassard O, Remy S, Dubart-Kupperschmitt A, Dagher I. Improving Hepatocyte Engraftment Following Hepatocyte Transplantation Using Repeated Reversible Portal Vein Embolization in Rats. Liver Transpl 2019; 25:98-110. [PMID: 30358068 DOI: 10.1002/lt.25364] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2018] [Accepted: 10/10/2018] [Indexed: 02/07/2023]
Abstract
Hepatocyte transplantation (HT) has emerged as a promising alternative to orthotopic liver transplantation, yet liver preconditioning is needed to promote hepatocyte engraftment. A method of temporary occlusion of the portal flow called reversible portal vein embolization (RPVE) has been demonstrated to be an efficient method of liver preconditioning. By providing an additional regenerative stimulus, repeated reversible portal vein embolization (RRPVE) could further boost liver engraftment. The aim of this study was to determine the efficiency of liver engraftment of transplanted hepatocytes after RPVE and RRPVE in a rat model. Green fluorescent protein-expressing hepatocytes were isolated from transgenic rats and transplanted into 3 groups of syngeneic recipient rats. HT was associated with RPVE in group 1, with RRPVE in group 2, and with sham embolization in the sham group. Liver engraftment was assessed at day 28 after HT on liver samples after immunostaining. Procedures were well tolerated in all groups. RRPVE resulted in increased engraftment rate in total liver parenchyma compared with RPVE (3.4% ± 0.81% versus 1.4% ± 0.34%; P < 0.001). In conclusion, RRPVE successfully enhanced hepatocyte engraftment after HT and could be helpful in the frame of failure of HT due to low cell engraftment.
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Affiliation(s)
- Martin Gaillard
- INSERM U1193, Hôpital Paul-Brousse, Villejuif, France.,Département Hospitalo-Universitaire Hepatinov, Hôpital Paul-Brousse, Villejuif, France.,Faculté de Médecine Paris-Sud, Université Paris-Saclay, Orsay, France.,Department of Minimally Invasive Surgery, Antoine Beclere Hospital, AP-HP, Clamart, France
| | - Hadrien Tranchart
- INSERM U1193, Hôpital Paul-Brousse, Villejuif, France.,Département Hospitalo-Universitaire Hepatinov, Hôpital Paul-Brousse, Villejuif, France.,Faculté de Médecine Paris-Sud, Université Paris-Saclay, Orsay, France.,Department of Minimally Invasive Surgery, Antoine Beclere Hospital, AP-HP, Clamart, France
| | - Panagiotis Lainas
- INSERM U1193, Hôpital Paul-Brousse, Villejuif, France.,Département Hospitalo-Universitaire Hepatinov, Hôpital Paul-Brousse, Villejuif, France.,Faculté de Médecine Paris-Sud, Université Paris-Saclay, Orsay, France.,Department of Minimally Invasive Surgery, Antoine Beclere Hospital, AP-HP, Clamart, France
| | - Olivier Trassard
- Institut Biomédical Bicêtre UMS32, Hôpital Bicetre, Kremlin-Bicetre, France
| | | | - Anne Dubart-Kupperschmitt
- INSERM U1193, Hôpital Paul-Brousse, Villejuif, France.,Département Hospitalo-Universitaire Hepatinov, Hôpital Paul-Brousse, Villejuif, France.,Faculté de Médecine Paris-Sud, Université Paris-Saclay, Orsay, France
| | - Ibrahim Dagher
- INSERM U1193, Hôpital Paul-Brousse, Villejuif, France.,Département Hospitalo-Universitaire Hepatinov, Hôpital Paul-Brousse, Villejuif, France.,Faculté de Médecine Paris-Sud, Université Paris-Saclay, Orsay, France.,Department of Minimally Invasive Surgery, Antoine Beclere Hospital, AP-HP, Clamart, France
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13
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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: 23] [Impact Index Per Article: 3.3] [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.
| | - A Dupré
- Inserm, LabTAU UMR1032, Centre Léon-Bérard, Université Claude-Bernard Lyon 1, 69003 Lyon, France
| | - 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
| | - 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
| | - J Gagnière
- Department of Digestive and Hepatobiliary Surgery, Hôpital Estaing, CHU Clermont-Ferrand, 1, place Lucie-et-Raymond-Aubrac, 63003 Clermont-Ferrand, France
| | - 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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14
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Hung ML, McWilliams JP. Portal vein embolization prior to hepatectomy: Techniques, outcomes and novel therapeutic approaches. INTERNATIONAL JOURNAL OF GASTROINTESTINAL INTERVENTION 2018. [DOI: 10.18528/gii180010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Affiliation(s)
- Matthew L. Hung
- Division of Interventional Radiology, Department of Radiology, UCLA Medical Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Justin P. McWilliams
- Division of Interventional Radiology, Department of Radiology, UCLA Medical Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
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15
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Functional shift with maintained regenerative potential following portal vein ligation. Sci Rep 2017; 7:18065. [PMID: 29273725 PMCID: PMC5741735 DOI: 10.1038/s41598-017-18309-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2017] [Accepted: 12/08/2017] [Indexed: 02/08/2023] Open
Abstract
Selective portal vein ligation (PVL) allows the two-stage surgical resection of primarily unresectable liver tumours by generating the atrophy and hypertrophy of portally ligated (LL) and non-ligated lobes (NLL), respectively. To evaluate critically important underlying functional alterations, present study characterised in vitro and vivo liver function in male Wistar rats (n = 106; 210-250 g) before, and 24/48/72/168/336 h after PVL. Lobe weights and volumes by magnetic resonance imaging confirmed the atrophy-hypertrophy complex. Proper expression and localization of key liver transporters (Ntcp, Bsep) and tight junction protein ZO-1 in isolated hepatocytes demonstrated constantly present viable and well-polarised cells in both lobes. In vitro taurocholate and bilirubin transport, as well as in vivo immunohistochemical Ntcp and Mrp2 expressions were bilaterally temporarily diminished, whereas LL and NLL structural acinar changes were divergent. In vivo bile and bilirubin-glucuronide excretion mirrored macroscopic changes, whereas serum bilirubin levels remained unaffected. In vivo functional imaging (indocyanine-green clearance test; 99mTc-mebrofenin hepatobiliary scintigraphy; confocal laser endomicroscopy) indicated transitionally reduced global liver uptake and -excretion. While LL functional involution was permanent, NLL uptake and excretory functions recovered excessively. Following PVL, functioning cells remain even in LL. Despite extensive bilateral morpho-functional changes, NLL functional increment restores temporary declined transport functions, emphasising liver functional assessment.
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16
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Comparable liver function and volume increase after portal vein embolization in rabbits and humans. Surgery 2017; 161:658-665. [DOI: 10.1016/j.surg.2016.08.039] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2016] [Revised: 08/13/2016] [Accepted: 08/30/2016] [Indexed: 12/12/2022]
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17
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Ma D, Yu ZY. Current status of research on liver regeneration. Shijie Huaren Xiaohua Zazhi 2016; 24:4193-4199. [DOI: 10.11569/wcjd.v24.i30.4193] [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
The liver has a strong regenerative potential, and liver regeneration shows different ways according to the degree of liver injury. The current research on liver regeneration has achieved some promising results, and the cellular and molecular mechanism of liver regeneration has been deeply studied. Recently, the role of biomechanical factors in liver regeneration is gradually attracting attention. In addition to the proliferation of liver cells, liver regeneration also involves the proliferation and differentiation of hepatic stem cells. However, the exact mechanism of liver regeneration is not fully clear. This review will summarize the relevant studies on liver regeneration to discuss the current research status of liver regeneration, with regard to the liver regeneration model, cellular and molecular mechanism of liver regeneration, the effects of mechanical factors on regeneration, and the role of stem cells in liver regeneration. A better understanding of liver regeneration will provide a new avenue for the clinical diagnosis and treatment of liver related diseases.
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