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1
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Vargas PA, Khanmammadova N, Balci D, Goldaracena N. Technical challenges in LDLT - Overcoming small for size syndrome and venous outflow reconstruction. Transplant Rev (Orlando) 2023; 37:100750. [PMID: 36878038 DOI: 10.1016/j.trre.2023.100750] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Revised: 01/22/2023] [Accepted: 02/21/2023] [Indexed: 03/03/2023]
Abstract
Living Donor Liver Transplantation (LDLT) emerged as an alternative treatment option for patients with end-stage liver disease waiting for an organ from a deceased donor. In addition to allowing for a faster access to transplantation, LDLT provides improved recipient outcomes when compared to deceased donor LT. However, it represents a more complex and demanding procedure for the transplant surgeon. In addition to a comprehensive preoperative donor assessment and stringent technical considerations during the donor hepatectomy to ensure upmost donor safety, the recipient procedure also comes with intrinsic challenges during LDLT. A proper approach during both procedures will result in favorable donor and recipient's outcomes. Hence, it is critical for the transplant surgeon to know how to overcome such technical challenges and avoid deleterious complications. One of the most feared complications following LDLT is small-for-size syndrome (SFSS). Although, surgical advances and deeper understanding of the pathophysiology behind SFSS has allowed for a safer implementation of LDLT, there is currently no consensus on the best strategy to prevent or manage this complication. Therefore, we aim to review current practices in technically challenging situations during LDLT, with a particular focus on management of small grafts and venous outflow reconstructions, as they possess one of the biggest technical challenges faced during LDLT.
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Affiliation(s)
- Paola A Vargas
- Department of Surgery, Division of Transplantation, University of Virginia Health System, Charlottesville, VA, USA
| | | | - Deniz Balci
- Bahçeşehir University School of Medicine Medical Park Göztepe Hospital, Liv Ulus Hospital, Istanbul, Turkey
| | - Nicolas Goldaracena
- Department of Surgery, Division of Transplantation, University of Virginia Health System, Charlottesville, VA, USA.
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2
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Cheng P, Li Z, Fu Z, Jian Q, Deng R, Ma Y. Small-For-Size Syndrome and Graft Inflow Modulation Techniques in Liver Transplantation. Dig Dis 2022; 41:250-258. [PMID: 35753308 DOI: 10.1159/000525540] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Accepted: 05/30/2022] [Indexed: 02/02/2023]
Abstract
BACKGROUND Partial liver transplantation has recently been proposed to alleviate organ shortages. However, transplantation of a small-for-size graft is associated with an increased risk of posttransplant hepatic dysfunction, commonly referred to as small-for-size syndrome (SFSS). This review describes the etiology, pathological features, clinical manifestations, and diagnostic criteria of SFSS. Moreover, we summarize strategies to improve graft function, focusing on graft inflow modulation techniques. Finally, unmet needs and future perspectives are discussed. SUMMARY In fact, posttransplant SFSS can be attributed to various factors such as preoperative status of the recipients, surgical techniques, donor age, and graft quality, except for graft size. With targeted improvement measures, satisfactory clinical outcomes can be achieved in recipients at increased risk of SFSS. Given the critical role of relative portal hyperperfusion in the pathogenesis of SFSS, various pharmacological and surgical treatments have been established to reduce or partially divert excessive portal inflow, and recipients will benefit from individualized therapeutic regimens after careful evaluation of benefits against potential risks. However, there remain unmet needs for further research into different aspects of SFSS to better understand the correlation between portal hemodynamics and patient outcomes. KEY MESSAGES Contemporary transplant surgeons should consider various donor and recipient factors and develop case-specific prevention and treatment strategies to improve graft and recipient survival rates.
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Affiliation(s)
- Pengrui Cheng
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Zhongqiu Li
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Zongli Fu
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Qian Jian
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Ronghai Deng
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yi Ma
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
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3
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Zou SF, Peng YH, Zheng CM, Fei YX, Zhao SW, Sun HP, Yang JF. Octreotide ameliorates hepatic ischemia-reperfusion injury through SNHG12/TAF15-mediated Sirt1 stabilization and YAP1 transcription. Toxicol Appl Pharmacol 2022; 442:115975. [PMID: 35307376 DOI: 10.1016/j.taap.2022.115975] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 02/23/2022] [Accepted: 03/05/2022] [Indexed: 02/07/2023]
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Bezinover D, Mukhtar A, Wagener G, Wray C, Blasi A, Kronish K, Zerillo J, Tomescu D, Pustavoitau A, Gitman M, Singh A, Saner FH. Hemodynamic Instability During Liver Transplantation in Patients With End-stage Liver Disease: A Consensus Document from ILTS, LICAGE, and SATA. Transplantation 2021; 105:2184-2200. [PMID: 33534523 DOI: 10.1097/tp.0000000000003642] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Hemodynamic instability (HDI) during liver transplantation (LT) can be difficult to manage and increases postoperative morbidity and mortality. In addition to surgical causes of HDI, patient- and graft-related factors are also important. Nitric oxide-mediated vasodilatation is a common denominator associated with end-stage liver disease related to HDI. Despite intense investigation, optimal management strategies remain elusive. In this consensus article, experts from the International Liver Transplantation Society, the Liver Intensive Care Group of Europe, and the Society for the Advancement of Transplant Anesthesia performed a rigorous review of the most current literature regarding the epidemiology, causes, and management of HDI during LT. Special attention has been paid to unique LT-associated conditions including the causes and management of vasoplegic syndrome, cardiomyopathies, LT-related arrhythmias, right and left ventricular dysfunction, and the specifics of medical and fluid management in end-stage liver disease as well as problems specifically related to portal circulation. When possible, management recommendations are made.
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Affiliation(s)
- Dmitri Bezinover
- Department of Anesthesiology and Perioperative Medicine, Pennsylvania State University, Penn State Health, Milton S. Hershey Medical Center, Hershey, PA. Represents ILTS and LICAGE
| | - Ahmed Mukhtar
- Department of Anesthesia and Surgical Intensive Care, Cairo University, Almanyal, Cairo, Egypt. Represents LICAGE
| | - Gebhard Wagener
- Department of Anesthesiology, Columbia University Medical Center, New York, NY. Represents SATA and ILTS
| | - Christopher Wray
- Department of Anesthesiology and Perioperative Medicine, University of California Los Angeles, Ronald Reagan Medical Center, Los Angeles, CA. Represents SATA
| | - Annabel Blasi
- Department of Anesthesia, IDIBAPS (Institut d´investigació biomèdica Agustí Pi i Sunyé) Hospital Clinic, Villaroel, Barcelona, Spain. Represents LICAGE and ILTS
| | - Kate Kronish
- Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, CA. Represents SATA
| | - Jeron Zerillo
- Department of Anesthesiology, Perioperative and Pain Medicine, Mount Sinai Hospital, Icahn School of Medicine at Mount Sinai, New York, NY. Represents SATA and ILTS
| | - Dana Tomescu
- Department of Anesthesiology and Intensive Care, Carol Davila University of Medicine and Pharmacy, Fundeni Clinical Institute, Bucharest, Romania. Represents LICAGE
| | - Aliaksei Pustavoitau
- Department of Anesthesia and Critical Care Medicine, Johns Hopkins Hospital, Johns Hopkins School of Medicine, Baltimore, MD. Represents ILTS
| | - Marina Gitman
- Department of Anesthesiology, University of Illinois Hospital, Chicago, IL. Represents SATA and ILTS
| | - Anil Singh
- Department of Liver Transplant and GI Critical Care, Sir HN Reliance Foundation Hospital, Cirgaon, Mumbai, India. Represents ILTS
| | - Fuat H Saner
- Department of General, Visceral and Transplant Surgery, Essen University Medical Center, Essen, Germany. Represents LICAGE
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5
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Bogner A, Reissfelder C, Striebel F, Mehrabi A, Ghamarnejad O, Rahbari M, Weitz J, Rahbari NN. Intraoperative Increase of Portal Venous Pressure is an Immediate Predictor of Posthepatectomy Liver Failure After Major Hepatectomy: A Prospective Study. Ann Surg 2021; 274:e10-e17. [PMID: 31356261 DOI: 10.1097/sla.0000000000003496] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVES The aim of this study was to assess intraoperative changes of hepatic macrohemodynamics and their association with ascites and posthepatectomy liver failure (PHLF) after major hepatectomy. SUMMARY OF BACKGROUND DATA Large-scale ascites and PHLF remain clinical challenges after major hepatectomy. No study has concomitantly evaluated arterial and venous liver macrohemodynamics in patients undergoing liver resection. METHODS Portal venous pressure (PVP), portal venous flow (PVF), and hepatic arterial flow (HAF) were measured intraoperatively pre- and postresection in 67 consecutive patients with major hepatectomy (ie, resection of ≥3 liver segments). A group of 30 patients with minor hepatectomy served as controls. Liver macrohemodynamics and their intraoperative changes (ie, Δ) were analyzed as predictive biomarkers of ascites and PHLF using Fisher exact, t test, or Wilcoxon rank sum test for univariate and logistic regression for multivariate analyses. RESULTS Major hepatectomy increased PVP by 26.9% (P = 0.001), markedly decreased HAF by 40.7% (P < 0.001), and slightly decreased PVF by 13.4% (P = 0.011). Minor resections had little effects on hepatic macrohemodynamics. There was no significant association of liver macrohemodynamics with ascites. While middle hepatic vein resection caused higher postresection PVP after right hepatectomy (P = 0.04), the Pringle maneuver was associated with a significant PVF (P = 0.03) and HAF reduction (P = 0.03). Uni- and multivariate analysis revealed an intraoperative PVP increase as an independent predictor of PHLF (P = 0.025). CONCLUSION Intraoperative PVP kinetics serve as independent predictive biomarker of PHLF after major hepatectomy. These data highlight the importance to assess intraoperative dynamics rather than the pre- and postresection PVP values.
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Affiliation(s)
- Andreas Bogner
- Department of General, Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, TU Dresden, Germany
| | - Christoph Reissfelder
- Department of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Fabian Striebel
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Arianeb Mehrabi
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Omid Ghamarnejad
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Mohammad Rahbari
- Department of General, Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, TU Dresden, Germany
| | - Jürgen Weitz
- Department of General, Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, TU Dresden, Germany
| | - Nuh N Rahbari
- Department of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
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6
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Explorative study of serum biomarkers of liver failure after liver resection. Sci Rep 2020; 10:9960. [PMID: 32561884 PMCID: PMC7305107 DOI: 10.1038/s41598-020-66947-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2019] [Accepted: 05/27/2020] [Indexed: 02/07/2023] Open
Abstract
Conventional biochemical markers have limited usefulness in the prediction of early liver dysfunction. We, therefore, tried to find more useful liver failure biomarkers after liver resection that are highly sensitive to internal and external challenges in the biological system with a focus on liver metabolites. Twenty pigs were divided into the following 3 groups: sham operation group (n = 6), 70% hepatectomy group (n = 7) as a safety margin of resection model, and 90% hepatectomy group (n = 7) as a liver failure model. Blood sampling was performed preoperatively and at 1, 6, 14, 30, 38, and 48 hours after surgery, and 129 primary metabolites were profiled. Orthogonal projection to latent structures-discriminant analysis revealed that, unlike in the 70% hepatectomy and sham operation groups, central carbon metabolism was the most significant factor in the 90% hepatectomy group. Binary logistic regression analysis was used to develop a predictive model for mortality risk following hepatectomy. The recommended variables were malic acid, methionine, tryptophan, glucose, and γ-aminobutyric acid. Area under the curve of the linear combination of five metabolites was 0.993 (95% confidence interval: 0.927–1.000, sensitivity: 100.0, specificity: 94.87). We proposed robust biomarker panels that can accurately predict mortality risk associated with hepatectomy.
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7
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Gallo G. The Role of Insulin in Hepatic Regeneration: A New Frontier in Liver Function. An Invited Brief Commentary on "Insulin Metabolism and Assessment of Hepatic Insulin Extraction During Liver Regeneration. A Study in a Rat Model". J INVEST SURG 2020; 33:77-78. [PMID: 30303704 DOI: 10.1080/08941939.2018.1488020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
Affiliation(s)
- Gaetano Gallo
- Department of Medical and Surgical Sciences, Operative Unit of General Surgery, Università degli Studi "Magna Graecia" di Catanzaro, Catanzaro, Italy
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8
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Faitot F, Ruhland E, Oncioiu C, Besch C, Addeo P, Cicek AE, Bachellier P, Namer IJ. Metabolomic profiling highlights the metabolic bases of acute-on-chronic and post-hepatectomy liver failure. HPB (Oxford) 2019; 21:1354-1361. [PMID: 30914156 DOI: 10.1016/j.hpb.2019.02.008] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2018] [Revised: 02/08/2019] [Accepted: 02/15/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND Posthepatectomy liver failure (PHLF) is the main limitation to extending liver resection but its pathophysiology is not yet fully understood. The aim of the study was to describe the metabolic adaptations that occur with PHLF. METHODS A retrospective study of 82 patients using nuclear magnetic resonance metabolomics to identify and quantify intra-hepatic metabolites was performed. The metabolite levels were compared using metabolic network analysis ADEMA between fatal PHLF (FLF) and non fatal PHLF and according to PHLF/ACLF grading. RESULTS Metabolomic profiles were significantly different between patients presenting FLF and non FLF or grade 3 ACLF versus < grade 3 ACLF. In the patients undergoing hepatectomy, valine, alanine and glycerophosphocholine were identified as powerful biomarkers to predict FLF (AUROC 0.806, 0.802 and 0.856 respectively). Network analysis showed an activation of aerobic glycolysis with glutaminolysis as observed in highly proliferating systems. Inversely, ACLF3 showed deprivation of glucose and lactate compared to lower ACLF grade. CONCLUSION Clinical andbiological severity of ACLF and PHLF correlate with specific metabolic adaptations. Metabolomics can predict fatal liver failure after hepatectomy and underline significant differences in the metabolic patterns of ACLF and PHLF.
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Affiliation(s)
- Francois Faitot
- Hepatobiliopancreatic Surgery and Transplantation Department, Hopital de Hautepierre, Hopitaux Universitaires de Strasbourg, France; Laboratoire ICube, UMR7357, University of Strasbourg, France.
| | - Elisa Ruhland
- Biophysics and Nuclear Medicine Department, Hopital de Hautepierre, Hopitaux Universitaires de Strasbourg, France
| | - Constantin Oncioiu
- Hepatobiliopancreatic Surgery and Transplantation Department, Hopital de Hautepierre, Hopitaux Universitaires de Strasbourg, France
| | - Camille Besch
- Hepatobiliopancreatic Surgery and Transplantation Department, Hopital de Hautepierre, Hopitaux Universitaires de Strasbourg, France
| | - Pietro Addeo
- Hepatobiliopancreatic Surgery and Transplantation Department, Hopital de Hautepierre, Hopitaux Universitaires de Strasbourg, France; Laboratoire ICube, UMR7357, University of Strasbourg, France
| | - A Ercument Cicek
- Lane Center of Computational Biology, School of Computer Science, Carnegie Mellon University, Pittsburgh, USA; Computer Engineering Department, Bilkent University, Ankara, Turkey
| | - Philippe Bachellier
- Hepatobiliopancreatic Surgery and Transplantation Department, Hopital de Hautepierre, Hopitaux Universitaires de Strasbourg, France
| | - Izzie-Jacques Namer
- Laboratoire ICube, UMR7357, University of Strasbourg, France; Biophysics and Nuclear Medicine Department, Hopital de Hautepierre, Hopitaux Universitaires de Strasbourg, France
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9
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Hessheimer AJ, Martínez de la Maza L, Adel Al Shwely F, Espinoza AS, Ausania F, Fondevila C. Somatostatin and the "Small-For-Size" Liver. Int J Mol Sci 2019; 20:2512. [PMID: 31121844 PMCID: PMC6566601 DOI: 10.3390/ijms20102512] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2019] [Revised: 05/07/2019] [Accepted: 05/14/2019] [Indexed: 02/07/2023] Open
Abstract
"Small-for-size" livers arising in the context of liver resection and transplantation are vulnerable to the effects of increased portal flow in the immediate postoperative period. Increased portal flow is an essential stimulus for liver regeneration. If the rise in flow and stimulus for regeneration are excessive; however, liver failure and patient death may result. Somatostatin is an endogenous peptide hormone that may be administered exogenously to not only reduce portal blood flow but also offer direct protection to different cells in the liver. In this review article, we describe key changes that transpire in the liver following a relative size reduction occurring in the context of resection and transplantation and the largely beneficial effects that peri-operative somatostatin therapy may help achieve in this setting.
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Affiliation(s)
- Amelia J Hessheimer
- Hepatopancreatobiliary Surgery and Transplantation, General & Digestive Surgery, Metabolic & Digestive Diseases Institute (ICMDM), Hospital Clínic, CIBERehd, IDIBAPS, University of Barcelona, 08036 Barcelona, Spain.
| | - Lilia Martínez de la Maza
- Hepatopancreatobiliary Surgery and Transplantation, General & Digestive Surgery, Metabolic & Digestive Diseases Institute (ICMDM), Hospital Clínic, CIBERehd, IDIBAPS, University of Barcelona, 08036 Barcelona, Spain.
| | - Farah Adel Al Shwely
- Hepatopancreatobiliary Surgery and Transplantation, General & Digestive Surgery, Metabolic & Digestive Diseases Institute (ICMDM), Hospital Clínic, CIBERehd, IDIBAPS, University of Barcelona, 08036 Barcelona, Spain.
| | - Arlena Sofía Espinoza
- Hepatopancreatobiliary Surgery and Transplantation, General & Digestive Surgery, Metabolic & Digestive Diseases Institute (ICMDM), Hospital Clínic, CIBERehd, IDIBAPS, University of Barcelona, 08036 Barcelona, Spain.
| | - Fabio Ausania
- Hepatopancreatobiliary Surgery and Transplantation, General & Digestive Surgery, Metabolic & Digestive Diseases Institute (ICMDM), Hospital Clínic, CIBERehd, IDIBAPS, University of Barcelona, 08036 Barcelona, Spain.
| | - Constantino Fondevila
- Hepatopancreatobiliary Surgery and Transplantation, General & Digestive Surgery, Metabolic & Digestive Diseases Institute (ICMDM), Hospital Clínic, CIBERehd, IDIBAPS, University of Barcelona, 08036 Barcelona, Spain.
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Aziz NM, Ragy MM, Ahmed SM. Somatostatin analogue, Octreotide, improves restraint stress-induced liver injury by ameliorating oxidative stress, inflammatory response, and activation of hepatic stellate cells. Cell Stress Chaperones 2018; 23:1237-1245. [PMID: 30109542 PMCID: PMC6237684 DOI: 10.1007/s12192-018-0929-7] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2018] [Revised: 07/06/2018] [Accepted: 08/02/2018] [Indexed: 12/17/2022] Open
Abstract
The aim of this study is to investigate the effect of somatostatin (SST) analogue, Octreotide, on some features of liver injury induced by immobilization stress (IS) in adult male albino rats. Eighteen adult male albino rats were randomly divided into three equal groups: control, IS, and Octreotide-treated stressed groups. Octreotide (40 μg/kg body weight, subcutaneously) was administrated twice daily for 8 days during the exposure to IS. Octreotide was found to reduce the IS significantly and induce elevations in the plasma level of corticosterone, liver transaminases, and tumor necrosis factor α (TNF-α) as compared with IS group. Furthermore, Octreotide administration has significantly elevated the decline in the total antioxidant capacities (TAC) and lowered the elevated malondialdehyde (MDA) levels observed with IS in the hepatic tissue. Additionally, Octreotide treatment provided protection against the histopathological changes in the stressed liver in the form of significant reduction in the mean number of degenerated hepatocytes, the area % of collagen fibers, and glial fibrillary acid protein (GFAP) immunostaining with a significant increase in the mean number of normal hepatocytes. In conclusion, stressed rats showed disturbed liver functions and its oxidant-antioxidant status with highly expression hepatic stellate cells (HSCs), which were all improved by Octreotide administration, SST analogue.
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Affiliation(s)
- Neven Makram Aziz
- Department of Physiology, Faculty of Medicine, Minia University, Minia, 61111, Egypt
- Deraya University, New Minia, Egypt
| | - Merhan Mamdouh Ragy
- Department of Physiology, Faculty of Medicine, Minia University, Minia, 61111, Egypt.
| | - Sabreen Mahmoud Ahmed
- Department of Physiology, Faculty of Medicine, Minia University, Minia, 61111, Egypt
- Department of Anatomy, Faculty of Medicine, Minia University, Minia, Egypt
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11
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Rajakumar A, Kaliamoorthy I, Rela M, Mandell MS. Small-for-Size Syndrome: Bridging the Gap Between Liver Transplantation and Graft Recovery. Semin Cardiothorac Vasc Anesth 2017; 21:252-261. [DOI: 10.1177/1089253217699888] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
In living donor liver transplantation, optimal graft size is estimated from values like graft volume/standard liver volume and graft/recipient body weight ratio but the final functional hepatic mass is influenced by other donor and recipient factors. Grafts with insufficient functional hepatic mass can produce a life-threatening condition with rapidly progressive liver failure called small-for-size syndrome (SFSS). Diagnosis of SFSS requires careful surveillance for signs of inadequate hepatocellular function, residual portal hypertension, and systemic inflammation that suggest rapidly progressive liver failure. Early diagnosis, symptom control, and addressing the cause of SFSS may prevent the need for retransplantation. With increased attention to avoiding donor risk, intensivists will be confronted with more SFSS recipients. In this review, we aim to outline a systematic approach to the medical management of patients with SFSS by providing a concise synopsis of general supportive care—neurological, cardiovascular, and renal support, mechanical ventilation, nutritional support, infection control, and tailored immunosuppression—with an aim to avoid end-organ damage or death and a review of current interventions including liver support devices, portal flow modulating drugs, and other experimental interventions that aim to preserve existing hepatic mass and improve conditions for hepatic regeneration. We examine evidence for SFSS interventions to provide the reader with information that may assist in clinical decision making. Points of controversy in care are purposefully highlighted to identify areas where additional experimental work is still needed. A full understanding of the pathophysiology of SFSS and measures to support liver regeneration will guide effective management.
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12
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Octreotide Attenuates Acute Kidney Injury after Hepatic Ischemia and Reperfusion by Enhancing Autophagy. Sci Rep 2017; 7:42701. [PMID: 28205545 PMCID: PMC5311976 DOI: 10.1038/srep42701] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2016] [Accepted: 01/10/2017] [Indexed: 12/16/2022] Open
Abstract
Octreotide exerts a protective effect in hepatic ischemia-reperfusion (HIR) injury. However, whether octreotide preconditioning could also reduce acute kidney injury (AKI) after HIR is unknown. This study was designed to investigate the role of octreotide in AKI after HIR. Male Sprague-Dawley rats were pretreated with octreotide or octreotide combined with 3-methyladenine (autophagy inhibitor, 3MA). Plasma creatinine, inflammation markers (e.g., TNF-α and IL-6 etc.), apoptosis, autophagy and phosphorylation of protein kinase B/mammalian target of rapamycin/p70 ribosomal S6 kinase (Akt/mTOR/p70S6K) in the kidney were measured after 60 minutes of liver ischemia and 24 hours of reperfusion for each rat. Octreotide pretreatment significantly preserved renal function and reduced the severity of renal injury. Moreover, octreotide alleviated inflammation and apoptosis in the kidney after HIR. Additionally, octreotide induced autophagy and autophagy inhibition with 3MA markedly reversed the renoprotective, anti-inflammatory and anti-apoptotic effects of octreotide after HIR. Finally, octreotide abrogated the activation of phosphorylation of Akt, mTOR and p70S6K in the kidney after HIR. Our results indicate that octreotide reduced renal injury after HIR due to its induction of autophagy. The enhancement of autophagy may be potentially linked to the octreotide mediated Akt/mTOR/p70S6K pathway deactivation and reduction of kidney inflammation and apoptosis after HIR.
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13
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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: 27] [Impact Index Per Article: 3.4] [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
| | - Juan Echeverri
- Multi Organ Transplant Program, Department of Surgery, Toronto General Hospital, Toronto, Ontario, Canada
| | - Markus Selzner
- Multi Organ Transplant Program, Department of Surgery, Toronto General Hospital, Toronto, Ontario, Canada
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Abstract
Liver regeneration has been studied for many decades and the mechanisms underlying regeneration of the normal liver following resection or moderate damage are well described. A large number of factors extrinsic (such as bile acids and circulating growth factors) and intrinsic to the liver interact to initiate and regulate liver regeneration. Less well understood, and more clinically relevant, are the factors at play when the abnormal liver is required to regenerate. Fatty liver disease, chronic scarring, prior chemotherapy and massive liver injury can all inhibit the normal programme of regeneration and can lead to liver failure. Understanding these mechanisms could enable the rational targeting of specific therapies to either reduce the factors inhibiting regeneration or directly stimulate liver regeneration. Although animal models of liver regeneration have been highly instructive, the clinical relevance of some models could be improved to bridge the gap between our in vivo model systems and the clinical situation. Likewise, modern imaging techniques such as spectroscopy will probably improve our understanding of whole-organ metabolism and how this predicts the liver's regenerative capacity. This Review describes briefly the mechanisms underpinning liver regeneration, the models used to study this process, and discusses areas in which failed or compromised liver regeneration is clinically relevant.
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Affiliation(s)
- Stuart J Forbes
- MRC Centre for Regenerative Medicine, 5 Little France Drive, University of Edinburgh, Edinburgh EH16 4UU, UK
| | - Philip N Newsome
- Birmingham National Institute for Health Research (NIHR) Liver Biomedical Research Unit and Centre for Liver Research, University of Birmingham, Vincent Drive Birmingham, B15 2TT, UK
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15
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Alikhanov RB, Sorokina AV, Zabozlaev FG, Panchenkov DN, Astakhov DA. [Role of octreotide and prednisolone in prophylactic of poshepatectomy liver failure. Experimental study]. Khirurgiia (Mosk) 2016:66-68. [PMID: 26977871 DOI: 10.17116/hirurgia2016266-68] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
AIM Comparative morphologic assessment of the liver tissue response to the preoperative infusion of octreotide and prednisolon after the major hepatic resection was studied in rats. MATERIAL AND METHODS 25 male Wistar rats weighing 230--280 g were used. All rats underwent 70--80% hepatectomy. The rats were divided into three groups according to the infusions before hepatectomy: group 1 (n=7) -- received octreotide, group 2 (n=8) -- prednisolone, group 3 (n=10) -- 0.9% saline solution as the control. Histologic features of the remnant liver were evaluated in the sacrificied rats after 72 hours post-hepatectomy. RESULTS In the group 1 we observed more rapid decrease of edema and tendency to the accelerated regeneration process of hepatocytes. CONCLUSION Octreotide infusion before the major hepatic resection may have protective effect on hepatocytes and accelerate the regeneration in the remnant liver.
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Affiliation(s)
- R B Alikhanov
- Moscow Clinical Scientific Center; Department of Surgery, M.V. Lomonosov Moscow State University
| | - A V Sorokina
- Department of Surgery, M.V. Lomonosov Moscow State University
| | - F G Zabozlaev
- Department of Surgery, Laboratory of Minimally Invasive Surgery
| | - D N Panchenkov
- Institute of Clinical Surgery, Federal Research Clinical Center of Specialized Medical Care and Medical Technologies FMBA A.I. Evdokimov Moscow State University of Medicine and Dentistry, Moscow, Russia
| | - D A Astakhov
- Institute of Clinical Surgery, Federal Research Clinical Center of Specialized Medical Care and Medical Technologies FMBA A.I. Evdokimov Moscow State University of Medicine and Dentistry, Moscow, Russia
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Tang GH, Yang HY, Zhang JC, Ren JJ, Sang XT, Lu X, Zhong SX, Mao YL. Magnesium isoglycyrrhizinate inhibits inflammatory response through STAT3 pathway to protect remnant liver function. World J Gastroenterol 2015; 21:12370-12380. [PMID: 26604644 PMCID: PMC4649120 DOI: 10.3748/wjg.v21.i43.12370] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2015] [Revised: 06/18/2015] [Accepted: 09/15/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the protective effect of magnesium isoglycyrrhizinate (MgIG) on excessive hepatectomy animal model and its possible mechanism.
METHODS: We used the standard 90% hepatectomy model in Sprague-Dawley rats developed using the modified Emond’s method, in which the left, middle, right upper, and right lower lobes of the liver were removed. Rats with 90% liver resection were divided into three groups, and were injected intraperitoneally with 3 mL saline (control group), 30 mg/kg (low-dose group) and 60 mg/kg (high-dose group) of MgIG, respectively. Animals were sacrificed at various time points and blood was drawn from the vena cava. Biochemical tests were performed with an automatic biochemical analyzer for the following items: serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamyl endopeptidase, total bilirubin (TBil), direct bilirubin (DBil), total protein, albumin, blood glucose (Glu), hyper-sensitivity C-reactive protein, prothrombin time (PT), and thrombin time (TT). Postoperative survival time was observed hourly until death. Hepatocyte regeneration was analyzed by immunohistochemistry. Serum inflammatory cytokines (IL-1, IL-6, IL-10, and iNOS) was analyzed by ELISA. STAT3 protein and mRNA were analyzed by Western blot and quantitative reverse-transcription PCR, respectively.
RESULTS: The high-dose group demonstrated a significantly prolonged survival time, compared with both the control and the low-dose groups (22.0 ± 4.7 h vs 8.9 ± 2.0 vs 10.3 ± 3.3 h, P = 0.018). There were significant differences among the groups in ALT, Glu and PT levels starting from 6 h after surgery. The ALT levels were significantly lower in the MgIG treated groups than in the control group. Both Glu and PT levels were significantly higher in the MgIG treated groups than in the control group. At 12 h, ALT, AST, TBil, DBil and TT levels showed significant differences between the MgIG treated groups and the control group. No significant differences in hepatocyte regeneration were found. Compared to the control group, the high-dose group showed a significantly increase in serum inflammatory cytokines IL-1 and IL-10, and a decrease in IL-6. Both STAT3 protein and mRNA levels were significantly lower in the MgIG treated groups than in the control group at 6 h, 12 h, and 18 h after surgery.
CONCLUSION: High-dose MgIG can extend survival time in rats after excessive hepatectomy. This hepatoprotective effect is mediated by inhibiting the inflammatory response through inhibition of the STAT3 pathway.
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