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Gómez-Gavara C, Moya-Herraiz Á, Hervás D, Pérez-Rojas J, LaHoz A, López-Andújar R. The Potential Role of Efficacy and Safety Evaluation of N-Acetylcysteine Administration During Liver Procurement. The NAC-400 Single Center Randomized Controlled Trial. Transplantation 2021; 105:2245-2254. [PMID: 33044432 DOI: 10.1097/tp.0000000000003487] [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: 11/27/2022]
Abstract
BACKGROUND N-acetylcysteine infusions have been widely used to reduce ischemia/reperfusion damage to the liver; however, convincing evidence of their benefits is lacking. OBJECTIVE To perform the largest randomized controlled trial to compare the impact of N-acetylcysteine infusion during liver procurement on liver transplant outcomes. METHODS Single center, randomized trial with patients recruited from La Fe University Hospital, Spain, from February 2012 to January 2016. A total of 214 grafts were transplanted and randomized to the N-acetylcysteine group (n = 113) or to the standard protocol without N-acetylcysteine (n = 101). The primary endpoint was allograft dysfunction (Olthoff criteria). Secondary outcomes included metabolomic biomarkers of oxidative stress levels, interactions between cold ischemia time and alanine aminotransferase level and graft and patient survival (ID no. NCT01866644). RESULTS The incidence of primary dysfunction was 34% (31% in the N-acetylcysteine group and 37.4% in the control group [P = 0.38]). N-acetylcysteine administration reduced the alanine aminotransferase level when cold ischemia time was longer than 6 h (P = 0.0125). Oxidative metabolites (glutathione/oxidized glutathione and ophthalmic acid) were similar in both groups (P > 0.05). Graft and patient survival rates at 12 mo and 3 y were similar between groups (P = 0.54 and P = 0.69, respectively). CONCLUSIONS N-acetylcysteine administration during liver procurement does not improve early allograft dysfunction according to the Olthoff classification. However, when cold ischemia time is longer than 6 h, N-acetylcysteine improves postoperative ALT levels.
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Affiliation(s)
- Concepción Gómez-Gavara
- Department of HPB Surgery and Transplants, Vall d'Hebron University Hospital, Barcelona, Spain
| | - Ángel Moya-Herraiz
- Department of HPB Surgery, Castellon General Hospital, CEU Cardenal Herrera University, Alfara del Patriarca, Spain
| | - David Hervás
- Statistics Unit, La Fe University Hospital, Valencia, Spain
| | - Judith Pérez-Rojas
- Pathological Anatomy Department, La Fe University Hospital, Valencia, Spain
| | - Agustín LaHoz
- Biomarkers and Precision Medicine Unit, IIS La Fe, Valencia, Spain
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Rao F, Yang J, Gong C, Huang R, Wang Q, Shen J. Systematic review of preservation solutions for allografts for liver transplantation based on a network meta-analysis. Int J Surg 2018; 54:1-6. [PMID: 29684666 DOI: 10.1016/j.ijsu.2018.04.024] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2018] [Revised: 04/09/2018] [Accepted: 04/12/2018] [Indexed: 01/20/2023]
Abstract
AIMS The aim of this work was to determine the best preservation solutions for allografts for liver transplantation by quantitative network meta-analysis. METHODS Global electronic databases including PubMed, EMBASE, and Cochrane Library were searched for relevant randomized controlled trials. Seven pieces of parametric data were extracted from included studies for pooled estimation. A consistency model was used for direct and indirect comparisons. The cumulative probability P value was utilized to rank the solutions. A node-splitting model was utilized for testing the consistency of final data. Quality of evidence was assessed using the GRADE (Grades of Recommendations Assessment, Development and Evaluation) system. RESULTS Eleven 2-arm trials including 1319 patients and 5 different solutions were finally included. HTK (Histidine-tryptophan-ketoglutarate) solution exhibited the best efficacy for decreasing the primary dysfunction rate, biliary complications and ICU-stay time (probability P = 0.43, 0.45 and 0.58, respectively). Celsior solution significantly decreased the rate of rejection and early retransplantation (probability P = 0.73 and 0.38, respectively), and enhanced patient and graft survival (probability P = 0.90 and 0.98, respectively) more than did other solutions. Overall, the quality of evidence was rated high or moderate. CONCLUSIONS We suggested that HTK solution may offer the best safety during the perioperative period. However, Celsior solution led to better graft tolerance and exhibited greater benefit for long-term outcomes. And our conclusions still need to be further validated.
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Affiliation(s)
- Fengying Rao
- School of Nursing, Huanggang Polytechnic College, Huanggang, 438002, PR China
| | - Jian Yang
- School of Nursing, Huanggang Polytechnic College, Huanggang, 438002, PR China
| | - Cheng Gong
- Department of General Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, PR China
| | - Rong Huang
- School of Nursing, Huanggang Polytechnic College, Huanggang, 438002, PR China
| | - Qi Wang
- The 1st Department of Gastrointestinal Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, PR China.
| | - Jun Shen
- Emergency Center, Zhongnan Hospital of Wuhan University, 430071, Hubei Province, PR China.
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Szilágyi ÁL, Mátrai P, Hegyi P, Tuboly E, Pécz D, Garami A, Solymár M, Pétervári E, Balaskó M, Veres G, Czopf L, Wobbe B, Szabó D, Wagner J, Hartmann P. Compared efficacy of preservation solutions on the outcome of liver transplantation: Meta-analysis. World J Gastroenterol 2018; 24:1812-1824. [PMID: 29713134 PMCID: PMC5922999 DOI: 10.3748/wjg.v24.i16.1812] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2018] [Revised: 04/02/2018] [Accepted: 04/09/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To compare the effects of the four most commonly used preservation solutions on the outcome of liver transplantations. METHODS A systematic literature search was performed using MEDLINE, Scopus, EMBASE and the Cochrane Library databases up to January 31st, 2017. The inclusion criteria were comparative, randomized controlled trials (RCTs) for deceased donor liver (DDL) allografts with adult and pediatric donors using the gold standard University of Wisconsin (UW) solution or histidine-tryptophan-ketoglutarate (HTK), Celsior (CS) and Institut Georges Lopez (IGL-1) solutions. Fifteen RCTs (1830 livers) were included; the primary outcomes were primary non-function (PNF) and one-year post-transplant graft survival (OGS-1). RESULTS All trials were homogenous with respect to donor and recipient characteristics. There was no statistical difference in the incidence of PNF with the use of UW, HTK, CS and IGL-1 (RR = 0.02, 95%CI: 0.01-0.03, P = 0.356). Comparing OGS-1 also failed to reveal any difference between UW, HTK, CS and IGL-1 (RR = 0.80, 95%CI: 0.80-0.80, P = 0.369). Two trials demonstrated higher PNF levels for UW in comparison with the HTK group, and individual studies described higher rates of biliary complications where HTK and CS were used compared to the UW and IGL-1 solutions. However, the meta-analysis of the data did not prove a statistically significant difference: the UW, CS, HTK and IGL-1 solutions were associated with nearly equivalent outcomes. CONCLUSION Alternative solutions for UW yield the same degree of safety and effectiveness for the preservation of DDLs, but further well-designed clinical trials are warranted.
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Affiliation(s)
| | - Péter Mátrai
- Institute of Bioanalysis, University of Pécs, Pécs H-7624, Hungary
| | - Péter Hegyi
- Institute for Translational Medicine and First Department of Medicine, University of Pécs, Pécs H-7624, Hungary
- MTA-SZTE Translational Gastroenterology Research Group, Szeged H-6720, Hungary
- János Szentágothai Research Center, University of Pécs, Pécs H-7624, Hungary
| | - Eszter Tuboly
- Institute of Surgical Research, University of Szeged, Szeged H-6720, Hungary
| | - Daniella Pécz
- Institute of Surgical Research, University of Szeged, Szeged H-6720, Hungary
| | - András Garami
- Institute for Translational Medicine and First Department of Medicine, University of Pécs, Pécs H-7624, Hungary
| | - Margit Solymár
- Institute for Translational Medicine and First Department of Medicine, University of Pécs, Pécs H-7624, Hungary
| | - Erika Pétervári
- Institute for Translational Medicine and First Department of Medicine, University of Pécs, Pécs H-7624, Hungary
| | - Márta Balaskó
- Institute for Translational Medicine and First Department of Medicine, University of Pécs, Pécs H-7624, Hungary
| | - Gábor Veres
- 1st Department of Paediatrics, University of Semmelweis, Budapest H-1085, Hungary
| | - László Czopf
- Department of Cardiology, 1st Department of Medicine, University of Pécs, Pécs H-7624, Hungary
| | - Bastian Wobbe
- Department of Cardiology, 1st Department of Medicine, University of Pécs, Pécs H-7624, Hungary
| | - Dorottya Szabó
- Department of Cardiology, 1st Department of Medicine, University of Pécs, Pécs H-7624, Hungary
| | - Juliane Wagner
- Department of Cardiology, 1st Department of Medicine, University of Pécs, Pécs H-7624, Hungary
| | - Petra Hartmann
- Institute of Surgical Research, University of Szeged, Szeged H-6720, Hungary
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Hameed AM, Laurence JM, Lam VWT, Pleass HC, Hawthorne WJ. A systematic review and meta-analysis of cold in situ perfusion and preservation of the hepatic allograft: Working toward a unified approach. Liver Transpl 2017; 23:1615-1627. [PMID: 28734125 PMCID: PMC5725662 DOI: 10.1002/lt.24829] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2017] [Revised: 05/03/2017] [Accepted: 07/16/2017] [Indexed: 01/01/2023]
Abstract
The efficacy of cold in situ perfusion and static storage of the liver is a possible determinant of transplantation outcomes. The aim of this study was to determine whether there is evidence to substantiate a preference for a particular perfusion route (aortic or dual) or perfusion/preservation solution in donation after brain death (DBD) liver transplantation. The Embase, MEDLINE, and Cochrane databases were used (1980-2017). Random effects modeling was used to estimate effects on transplantation outcomes based on (1) aortic or dual in situ perfusion and (2) the use of University of Wisconsin (UW), histidine tryptophan ketoglutarate (HTK), Celsior, and/or Institut Georges Lopez-1 (IGL-1) solutions for perfusion/preservation. A total of 22 articles were included (2294 liver transplants). The quality of evidence ranged from very low to moderate Grading of Recommendations, Assessment, Development and Evaluations score. Meta-analyses were conducted for 14 eligible studies. Although there was no difference in the primary nonfunction (PNF) rate, a higher peak alanine aminotransferase (ALT) was recorded in dual compared with aortic-only UW-perfused livers (standardized mean difference, 0.24; 95% confidence interval, 0.01-0.47); a back-table portal venous flush was undertaken in the majority of aortic-only perfused livers. There were no relevant differences in peak enzymes, PNF, thrombotic graft loss, biliary complications, or 1-year graft survival in comparisons between dual-perfused livers using UW, HTK, Celsior, or IGL-1. In conclusion, there is no significant evidence that aortic-only perfusion of the DBD liver compromises transplantation outcomes, and it may be favored because of its simplicity. However, there is currently insufficient evidence to advocate for the use of any particular perfusion/preservation fluid over the others. Liver Transplantation 23 1615-1627 2017 AASLD.
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Affiliation(s)
- Ahmer M. Hameed
- Centre for Transplant and Renal Research, Westmead Institute for Medical ResearchWestmeadNew South WalesAustralia,Department of SurgeryWestmead HospitalWestmeadNew South WalesAustralia,Sydney Medical SchoolUniversity of SydneySydneyNew South WalesAustralia
| | - Jerome M. Laurence
- Sydney Medical SchoolUniversity of SydneySydneyNew South WalesAustralia,Department of Surgery,Institute of Academic Surgery, Royal Prince Alfred HospitalUniversity of SydneyCamperdownNew South WalesAustralia
| | - Vincent W. T. Lam
- Department of SurgeryWestmead HospitalWestmeadNew South WalesAustralia,Sydney Medical SchoolUniversity of SydneySydneyNew South WalesAustralia
| | - Henry C. Pleass
- Department of SurgeryWestmead HospitalWestmeadNew South WalesAustralia,Sydney Medical SchoolUniversity of SydneySydneyNew South WalesAustralia,Department of Surgery
| | - Wayne J. Hawthorne
- Centre for Transplant and Renal Research, Westmead Institute for Medical ResearchWestmeadNew South WalesAustralia,Department of SurgeryWestmead HospitalWestmeadNew South WalesAustralia,Sydney Medical SchoolUniversity of SydneySydneyNew South WalesAustralia
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Fahrner R, Dondorf F, Ardelt M, Settmacher U, Rauchfuss F. Role of NK, NKT cells and macrophages in liver transplantation. World J Gastroenterol 2016; 22:6135-6144. [PMID: 27468206 PMCID: PMC4945975 DOI: 10.3748/wjg.v22.i27.6135] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2016] [Revised: 05/25/2016] [Accepted: 06/15/2016] [Indexed: 02/07/2023] Open
Abstract
Liver transplantation has become the treatment of choice for acute or chronic liver disease. Because the liver acts as an innate immunity-dominant organ, there are immunological differences between the liver and other organs. The specific features of hepatic natural killer (NK), NKT and Kupffer cells and their role in the mechanism of liver transplant rejection, tolerance and hepatic ischemia-reperfusion injury are discussed in this review.
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Latchana N, Peck JR, Whitson BA, Henry ML, Elkhammas EA, Black SM. Preservation solutions used during abdominal transplantation: Current status and outcomes. World J Transplant 2015; 5:154-164. [PMID: 26722644 PMCID: PMC4689927 DOI: 10.5500/wjt.v5.i4.154] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2015] [Revised: 09/01/2015] [Accepted: 11/11/2015] [Indexed: 02/05/2023] Open
Abstract
Organ preservation remains an important contributing factor to graft and patient outcomes. During donor organ procurement and transportation, cellular injury is mitigated through the use of preservation solutions in conjunction with hypothermia. Various preservation solutions and protocols exist with widespread variability among transplant centers. In this review of abdominal organ preservation solutions, evolution of transplantation and graft preservation are discussed followed by classification of preservation solutions according to the composition of electrolytes, impermeants, buffers, antioxidants, and energy precursors. Lastly, pertinent clinical studies in the setting of hepatic, renal, pancreas, and intestinal transplantation are reviewed for patient and graft survival as well as financial considerations. In liver transplants there may be some benefit with the use of histidine-tryptophan-ketoglutarate (HTK) over University of Wisconsin solution in terms of biliary complications and potential cost savings. Renal grafts may experience increased initial graft dysfunction with the use of Euro-Collins thereby dissuading its use in support of HTK which can lead to substantial cost savings. University of Wisconsin solution and Celsior are favored in pancreas transplants given the concern for pancreatitis and graft thrombosis associated with HTK. No difference was observed with preservation solutions with respect to graft and patient survival in liver, renal, and pancreas transplants. Studies involving intestinal transplants are sparse but University of Wisconsin solution infused intraluminally in combination with an intra-vascular washout is a reasonable option until further evidence can be generated. Available literature can be used to ameliorate extensive variation across centers while potentially minimizing graft dysfunction and improving associated costs.
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Yang MM, Huang W, Jiang DM. Tetramethylpyrazine protects Schwann cells from ischemia-like injury and increases cell survival in cold ischemic rat nerves. BRAZ J PHARM SCI 2015. [DOI: 10.1590/s1984-82502015000100014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Tetramethylpyrazine (TMP), a major active ingredient of Ligusticum wallichi Franchat extract (a Chinese herb), exhibits neuroprotective properties in ischemia. In this study, we assessed its protective effects on Schwann cells (SCs) by culturing them in the presence of oxygen glucose deprivation (OGD) conditions and measuring cell survival in cold ischemic rat nerves. In the OGD-induced ischemic injury model of SCs, we demonstrated that TMP treatment not only reduced OGD-induced cell viability losses, cell death, and apoptosis of SCs in a dose-dependent manner, and inhibited LDH release, but also suppressed OGD-induced downregulation of Bcl-2 and upregulation of Bax and caspase-3, as well as inhibited the consequent activation of caspase-3. In the cold ischemic nerve model, we found that prolonged cold ischemic exposure for four weeks was markedly associated with the absence of SCs, a decrease in cell viability, and apoptosis in preserved nerve segments incubated in University of Wisconsin solution (UWS) alone. However, TMP attenuated nerve segment damage by preserving SCs and antagonizing the decrease in nerve fiber viability and increase in TUNEL-positive cells in a dose-dependent manner. Collectively, our results indicate that TMP not only provides protective effects in an ischemia-like injury model of cultured rat SCs by regulating Bcl-2, Bax, and caspase-3, but also increases cell survival and suppresses apoptosis in the cold ischemic nerve model after prolonged ischemic exposure for four weeks. Therefore, TMP may be a novel and effective therapeutic strategy for preventing peripheral nervous system ischemic diseases and improving peripheral nerve storage.
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Affiliation(s)
- Ming-Ming Yang
- Chongqing Medical University, People's Republic of China
| | - Wei Huang
- Chongqing Medical University, People's Republic of China
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Savier E, Granger B, Charlotte F, Cormillot N, Siksik JM, Vaillant JC, Hannoun L. Liver preservation with SCOT 15 solution decreases posttransplantation cholestasis compared with University of Wisconsin solution: a retrospective study. Transplant Proc 2014; 43:3402-7. [PMID: 22099807 DOI: 10.1016/j.transproceed.2011.09.054] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND SCOT 15 is a new solution to preserve abdominal organs for transplantation. Its principal characteristic is the use of polyethylene glycol. Herein We report our experience using SCOT 15 compared with the reference University of Wisconsin (UW) solution for hepatic transplantation. METHODS We compared 2 groups: SCOT 15 (n = 33; 2009-2010) versus UW (n = 34; 2008-2010), which were paired for cold and warm ischemic times, donor ages, and graft weights. Endpoints were biologic tests in the first 2 months after the operation. A linear mixed model was used to evaluate longitudinal changes and influences of each solution. RESULTS No primary failure was observed. At postoperative day 0, transaminase values were higher in the SCOT 15 than in the UW group: aspartate transaminase: 2,435 ± 399 vs 589 ± 83 IU/L (P < .01); alanine transaminase: ALT: 1,207 ± 191 vs 484 ± 64 IU/L (P < .05), then returned to low levels in both groups. From day 0 to 8, coagulation factors reached normal values; there was no difference between the 2 groups. Total bilirubin decreased similarly in the 2 groups. However, from the second postoperative week (W1) to W8, the SCOT 15 group showed a slow decrease in the mean values of gamma-glutamyltranspeptidase (gGT) from 233 ± 125 to 130 ± 161 IU/L, which were significantly lower than those in the UW group, where the gGT remained around 300 IU/L (P < .01). The End-Stage Liver Disease, Child-Pugh, or United Network for Organ Sharing scores, primary liver diseases, hepatitic C virus status, arterial or biliary complications, and male/female ratio, which was different in the 2 groups, did not statistically influence these results. CONCLUSIONS The main effect of cold storage of human liver using SCOT 15 compared with UW solution was to decrease cholestasis following transplantation.
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Affiliation(s)
- E Savier
- Service de Chirurgie Digestive et Hépato-Bilio-Pancréatique-Transplantation Hépatique, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
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The effect of preservation solutions for storage of liver allografts on transplant outcomes: a systematic review and meta-analysis. Ann Surg 2014; 260:46-55. [PMID: 24374537 DOI: 10.1097/sla.0000000000000402] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
OBJECTIVE The objective of this review was to systematically evaluate the evidence comparing preservation fluids for liver allografts on transplant outcomes. BACKGROUND Adequate preservation of liver allografts for transplantation is essential for successful transplant outcomes. There are several preservation fluids available that have been specifically designed for the static cold storage of livers. These fluids differ in composition and cost. METHODS literature search was performed using MEDLINE, EMBASE, Cochrane Library, Transplant Library, and the International Clinical Trials Registry Platform. Only randomized controlled trials were included. Studies were assessed for methodological quality. Primary outcomes were the risk of early dysfunction, primary nonfunction, retransplantation, patient survival, and graft survival. Secondary outcomes were serum biochemical parameters in the first week and biliary complications. Summary effects were calculated as relative risk and relative log survival with 95% confidence intervals (95% CIs). RESULTS Sixteen randomized controlled trials met the full inclusion criteria (1619 livers). There is good evidence that the University of Wisconsin and Celsior solutions are associated with the same rates of early dysfunction (relative risk = 1.08, 95% CI = 0.63-1.86, P = 0.77), primary nonfunction (relative risk = 0.73, 95% CI = 0.22-2.40, P = 0.60), patient survival (relative log survival = 0.86, 95% CI = 0.58-1.28, P = 0.46), and graft survival (relative log survival = 0.85, 95% CI = 0.59-1.23, P = 0.39). There was no good evidence of any difference in outcomes when comparing histidine-tryptophan-ketoglutarate with either of the University of Wisconsin or Celsior solution, although data were limited. CONCLUSIONS Data from included studies suggest that preservation of deceased donor livers with the University of Wisconsin or Celsior solution results in equivalent outcomes.
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Liu H, Yu Y, Glorioso J, Mao S, Rodysil B, Amiot BP, Rinaldo P, Nyberg SL. Cold Storage of Rat Hepatocyte Spheroids. Cell Transplant 2014; 23:819-30. [DOI: 10.3727/096368913x664847] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Cell-based therapies for liver disease rely on a high-quality supply of hepatocytes and a means for storage during transportation from site of isolation to site of usage. Unfortunately, frozen cryopreservation is associated with unacceptable loss of hepatocyte viability after thawing. The purpose of this study was to optimize conditions for cold storage of rat hepatocyte spheroids without freezing. Rat hepatocytes were isolated by a two-step perfusion method; hepatocyte spheroids were formed during 48 h of rocked culture in serum-free medium (SFM). Spheroids were then maintained in rocked culture at 37°C (control condition) or cold stored at 4°C for 24 or 48 h in six different cold storage solutions: SFM alone; SFM + 1 mM deferoxamine (Def); SFM + 1 μM cyclosporin A (CsA); SFM + 1 mM Def + 1 μM CsA, University of Wisconsin (UW) solution alone, UW + 1 mM Def. Performance metrics after cold storage included viability, gene expression, albumin production, and functional activity of cytochrome P450 enzymes and urea cycle proteins. We observed that cold-induced injury was reduced significantly by the addition of the iron chelator (Def) to both SFM and UW solution. Performance metrics (ammonia detoxification, albumin production) of rat hepatocyte spheroids stored in SFM + Def for 24 h were significantly increased from SFM alone and approached those in control conditions, while performance metrics after cold storage in SFM alone or cold storage for 48 h were both significantly reduced. A serum-free medium supplemented with Def allowed hepatocyte spheroids to tolerate 24 h of cold storage with less than 10% loss in viability and functionality. Further research is warranted to optimize a solution for extended cold storage of hepatocyte spheroids.
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Affiliation(s)
- Hongling Liu
- Division of Experimental Surgery, Mayo Clinic College of Medicine, Rochester, MN, USA
- Liver Failure Diagnosis and Treatment Center, 302 Military Hospital, Beijing, P.R. China
| | - Yue Yu
- Division of Experimental Surgery, Mayo Clinic College of Medicine, Rochester, MN, USA
- Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, P.R. China
| | - Jaime Glorioso
- Division of Experimental Surgery, Mayo Clinic College of Medicine, Rochester, MN, USA
| | - Shennen Mao
- Division of Experimental Surgery, Mayo Clinic College of Medicine, Rochester, MN, USA
| | - Brian Rodysil
- Division of Experimental Surgery, Mayo Clinic College of Medicine, Rochester, MN, USA
| | | | - Piero Rinaldo
- Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN, USA
| | - Scott L. Nyberg
- Division of Experimental Surgery, Mayo Clinic College of Medicine, Rochester, MN, USA
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Voigt MR, DeLario GT. Perspectives on abdominal organ preservation solutions: a comparative literature review. Prog Transplant 2014; 23:383-91. [PMID: 24311404 DOI: 10.7182/pit2013100] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Various preservation solutions are used for kidney, liver, pancreas, small intestine, and multiorgan recoveries and transplants. The effectiveness of these solutions, primarily measured by ability to preserve the organ and graft survival, was analyzed. The 2 most common solutions used for intra-abdominal organs are University of Wisconsin Solution (UW)/Viaspan and Histidine-tryptophan-ketoglutarate (HTK)/Custodiol solution. Outcomes for liver, pancreas, and kidney allografts preserved with these 2 solutions are similar. Although HTK solution shows conflicting results with respect to pancreatic cellular edema, researchers in several studies have noted that HTK solution may be more protective than UW solution against biliary complications in liver transplant. In kidney recoveries, HTK solution may be associated with higher graft loss and increased delayed graft function in marginal deceased donors but had lower incidence of delayed graft function in living donors when compared with UW. UW remains the reference standard for use during multiorgan recoveries but is experiencing strong competition from HTK and other alternative solutions. Some researchers suggest that Celsior's comparable results in abdominal organs and viability for thoracic organs makes it a strong competitor, especially in multiorgan recoveries. Each solution has benefits accompanied by disadvantages. Although it may not be feasible, when considering single-organ recoveries, consideration of alternative solutions may be warranted.
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12
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Liu Q, Izamis ML, Xu H, Berendsen T, Yarmush M, Uygun K. Strategies to rescue steatotic livers before transplantation in clinical and experimental studies. World J Gastroenterol 2013; 19:4638-4650. [PMID: 23922462 PMCID: PMC3732837 DOI: 10.3748/wjg.v19.i29.4638] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2012] [Revised: 12/07/2012] [Accepted: 12/17/2012] [Indexed: 02/06/2023] Open
Abstract
The shortage of donor livers has led to an increased use of organs from expanded criteria donors. Included are livers with steatosis, a metabolic abnormality that increases the likelihood of graft complications post-transplantation. After a brief introduction on the etiology, pathophysiology, categories and experimental models of hepatic steatosis, we herein review the methods to rescue steatotic donor livers before transplantation applied in clinical and experimental studies. The methods span the spectrum of encouraging donor weight loss, employing drug therapy, heat shock preconditioning, ischemia preconditioning and selective anesthesia on donors, and the treatment on isolated grafts during preservation. These methods work at different stages of transplantation process, although share similar molecular mechanisms including lipid metabolism stimulation through enzymes or nuclear receptor e.g., peroxisomal proliferator-activated receptor, or anti-inflammation through suppressing cytokines e.g., tumor necrosis factor-α, or antioxidant therapies to alleviate oxidative stress. This similarity of molecular mechanisms implies possible future attempts to reinforce each approach by repeating the same treatment approach at several stages of procurement and preservation, as well as utilizing these alternative approaches in tandem.
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13
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van Egmond A, van der Keur C, Swings GMJS, van Beelen E, van Zijl L, Scherjon SA, Claas FHJ. Preservation of human placenta facilitates multicenter studies on the local immune response in normal and aberrant pregnancies. J Reprod Immunol 2013; 98:29-38. [PMID: 23623053 DOI: 10.1016/j.jri.2013.03.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2012] [Revised: 02/27/2013] [Accepted: 03/04/2013] [Indexed: 01/03/2023]
Abstract
Our standard procedure for phenotypic and functional analysis of immune cells present in the placenta is to isolate leukocytes from the decidua within five hours of the delivery. However, this results in logistical problems with deliveries at night, weekends or in other medical centers. Collecting placentas after complicated pregnancies is even more difficult owing to the low prevalence and the often unscheduled delivery. The aim was to investigate the possibility of preserving the human placenta before phenotypic and functional analysis of decidual lymphocytes. Placentas were obtained after uncomplicated pregnancy. The tissue was divided into two equal parts: decidual lymphocytes from one part were isolated within five hours according to our standard procedure, whereas the other part was preserved in either Celsior(®), a storage solution for solid organ preservation, or phosphate-buffered saline (PBS) for 24h at 4°C before isolation. Overall, the phenotype and functional capacity of decidual lymphocytes isolated within five hours was comparable to decidual lymphocytes isolated after 24-h preservation in Celsior(®) or PBS. Minor differences were found between decidual lymphocytes isolated within five hours and decidual lymphocytes isolated after 24-h preservation in Celsior(®). The results indicate that PBS is sufficient to preserve the placenta for 24h for phenotypical and functional studies. The ability to preserve the placenta will simplify the procedure for the isolation of decidual lymphocytes and makes it easier to analyze tissue from women who deliver during the night, at weekends or in other hospitals, and possibly even women with complicated pregnancies.
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Affiliation(s)
- A van Egmond
- Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
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Gastaca M. Biliary complications after orthotopic liver transplantation: a review of incidence and risk factors. Transplant Proc 2013; 44:1545-9. [PMID: 22841209 DOI: 10.1016/j.transproceed.2012.05.008] [Citation(s) in RCA: 75] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Biliary complications (BCs) are a common source of morbidity after liver transplantation, leading to long-term and repeated therapies. The incidence of BCs currently ranges from 5% and 25%. Biliary strictures and leaks are the most common complications after deceased donor liver transplantation (DDLT), occurring in 9%-12% and 5%-10% of cases, respectively. Hepatic artery complications are recognized as the major risk factor for BCs; however, other circumstances such as advanced donor age, prolonged cold and warm ischemia times, grafts from donors after cardiac death, occurrence of a previous bile leak, T-tube use, cytomegalovirus infection, or graft steatosis have also been reported to be potential risk factors. Use of various preservation solutions has not significantly improved the biliary complication rate after DDLT. Technical modifications in biliary reconstruction have been proposed to improve outcomes after DDLT; the use of a T-tube for biliary reconstruction continues to be controversial. Non anastomotic strictures (NAS) are recognized to be different from anastomotic strictures. Although they have been associated with ischemic or immunological mechanisms, bile salt toxicity has recently been recognized as a potential factor for NAS. Donation after cardiac death is a significant source of organs that has been associated with decreased graft survival due to the increased BCs.
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Affiliation(s)
- M Gastaca
- Hepato-Biliary Surgery and Liver Transplantation Unit, Hospital Universitario de Cruces, Bilbao, Spain.
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Preservation solutions for liver transplantation in adults: celsior versus custodiol: a systematic review and meta-analysis with an indirect comparison of randomized trials. Transplant Proc 2012; 45:25-32. [PMID: 23267794 DOI: 10.1016/j.transproceed.2012.02.031] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2011] [Accepted: 02/28/2012] [Indexed: 12/11/2022]
Abstract
BACKGROUND The University of Wisconsin (UW) solution has been recognized as the gold standard for liver preservation; however, it possesses some limitations, and other solutions exist for organ preservation. The aim of this study was to compare the liver functions of transplanted grafts that had been stored in Celsior and Custodiol solutions. METHODS We searched the MEDLINE, EMBASE, LILACS, Cochrane Central Register of Controlled Trials, and SCIELO databases. We included randomized and quasi-randomized, controlled trials that compared the efficacy and safety of Celsior and Custodiol with UW solution for liver preservation in adults. The factors that were considered for analysis were their impacts on primary dysfunction (primary nonfunction and initial poor function), ischemic-type biliary lesions, and patient and graft survival rates. Because of the lack of direct evidence, an indirect comparison of Celsior and Custodiol was calculated. RESULTS We identified 3 randomized controlled trials and 1 quasi-randomized, controlled trial to pool in a meta-analysis of Celsior versus UW solutions. The number of episodes of primary dysfunction was lower in the Celsior group (7.4%) than in the UW group (9.8%), but the difference was not significant (relative risk [RR], 0.68; 95% confidence interval [CI], 0.22-1.97). Two randomized controlled trials compared Custodiol and Wisconsin solutions were identified. The number of episodes of primary dysfunction was also lower in the Custodiol group (3.0%) compared with the Wisconsin group (8.4%), but the difference was not significant (RR, 0.36; 95% CI, 0.08-1.70). An indirect comparison using data from the main analysis revealed no difference between the Celsior and Custodiol solutions (RR, 1.88; 95% CI, 0.57-6.16). CONCLUSION The Celsior and Custodiol solutions performed similarly to UW solution as preservation solutions in liver transplantation clinical settings.
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García-Gil FA, Serrano MT, Fuentes-Broto L, Arenas J, García JJ, Güemes A, Bernal V, Campillo A, Sostres C, Araiz JJ, Royo P, Simón MA. Celsior versus University of Wisconsin preserving solutions for liver transplantation: postreperfusion syndrome and outcome of a 5-year prospective randomized controlled study. World J Surg 2011; 35:1598-607. [PMID: 21487851 DOI: 10.1007/s00268-011-1078-7] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Celsior solution (CS) is a high-sodium, low-potassium, low-viscosity extracellular solution that has been used for liver graft preservation in recent years, although experience with it is still limited. We performed an open-label randomized active-controlled trial comparing CS with the University of Wisconsin solution (UW) for liver transplantation (LT), with a follow-up period of 5 years. METHODS Adult transplant recipients (n=102) were prospectively randomized to receive either CS (n=51) or UW (n=51). The two groups were comparable with respect to donor and recipient characteristics. The primary outcome measure was the incidence of postreperfusion syndrome (PRS). Secondary outcome measures included primary nonfunction (PNF) or primary dysfunction (PDF), liver retransplantation, and graft and patient survival. Other secondary outcome measures were days in the intensive care unit (ICU) and the rates of acute rejection, chronic rejection, infectious complications, postoperative reoperations, and vascular and biliary complications. RESULTS In all, 14 posttransplant variables revealed no significant differences between the groups. There were no cases of PNF or PDF. The incidence of PRS was 5.9% in the CS group and 21.6% in the UW group (P=0.041). After reperfusion, CS revealed greater control of serum potassium (P=0.015), magnesium levels (P=0.005), and plasma glucose (P=0.042) than UW. Respective patient survivals at 3, 12, and 60 months were 95.7, 87.2, and 82.0% for the CS group and 95.7, 83.3, and 66.6% for the UW group (P=0.123). CONCLUSIONS While retaining the same degree of safety and effectiveness as UW for LT, CS may yield postliver graft reperfusion benefits, as shown in this study by a significant reduction in the incidence of PRS and greater metabolic control.
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Affiliation(s)
- Francisco A García-Gil
- Department of Surgery, University of Zaragoza, Domingo Miral s/n, 50009, Zaragoza, Spain.
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Hypothermic kidney preservation: a remembrance of the past in the future? Curr Opin Organ Transplant 2011; 16:162-8. [DOI: 10.1097/mot.0b013e3283446b07] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
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Guibert EE, Petrenko AY, Balaban CL, Somov AY, Rodriguez JV, Fuller BJ. Organ Preservation: Current Concepts and New Strategies for the Next Decade. Transfus Med Hemother 2011; 38:125-142. [PMID: 21566713 PMCID: PMC3088735 DOI: 10.1159/000327033] [Citation(s) in RCA: 206] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2011] [Accepted: 01/26/2011] [Indexed: 12/12/2022] Open
Abstract
SUMMARY: Organ transplantation has developed over the past 50 years to reach the sophisticated and integrated clinical service of today through several advances in science. One of the most important of these has been the ability to apply organ preservation protocols to deliver donor organs of high quality, via a network of organ exchange to match the most suitable recipient patient to the best available organ, capable of rapid resumption of life-sustaining function in the recipient patient. This has only been possible by amassing a good understanding of the potential effects of hypoxic injury on donated organs, and how to prevent these by applying organ preservation. This review sets out the history of organ preservation, how applications of hypothermia have become central to the process, and what the current status is for the range of solid organs commonly transplanted. The science of organ preservation is constantly being updated with new knowledge and ideas, and the review also discusses what innovations are coming close to clinical reality to meet the growing demands for high quality organs in transplantation over the next few years.
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Affiliation(s)
- Edgardo E. Guibert
- Centro Binacional (Argentina-Italia) de Investigaciones en Criobiología Clínica y Aplicada (CAIC), Universidad Nacional de Rosario, Argentina
| | - Alexander Y. Petrenko
- Department of Cryobiochemistry, Institute for Problems of Cryobiology and Cryomedicine, Ukraine Academy of Sciences, Kharkov, Ukraine
| | - Cecilia L. Balaban
- Centro Binacional (Argentina-Italia) de Investigaciones en Criobiología Clínica y Aplicada (CAIC), Universidad Nacional de Rosario, Argentina
| | - Alexander Y. Somov
- Department of Cryobiochemistry, Institute for Problems of Cryobiology and Cryomedicine, Ukraine Academy of Sciences, Kharkov, Ukraine
| | - Joaquín V. Rodriguez
- Centro Binacional (Argentina-Italia) de Investigaciones en Criobiología Clínica y Aplicada (CAIC), Universidad Nacional de Rosario, Argentina
| | - Barry J. Fuller
- Cell, Tissue and Organ Preservation Unit, Department of Surgery & Liver Transplant Unit, UCL Medical School, Royal Free Hospital Campus, London, UK
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Abstract
During liver resection surgery for cancer or liver transplantation, the liver is subject to ischaemia (reduction in blood flow) followed by reperfusion (restoration of blood flow), which results in liver injury [ischemia-reperfusion (IR) or IR injury]. Modulation of IR injury can be achieved in various ways. These include hypothermia, ischaemic preconditioning (IPC) (brief cycles of ischaemia followed by reperfusion of the organ before the prolonged period of ischaemia i.e. a conditioning response), ischaemic postconditioning (conditioning after the prolonged period of ischaemia but before the reperfusion), pharmacological agents to decrease IR injury, genetic modulation of IR injury, and machine perfusion (pulsatile perfusion). Hypothermia decreases the metabolic functions and the oxygen consumption of organs. Static cold storage in University of Wisconsin solution reduces IR injury and has prolonged organ storage and improved the function of transplanted grafts. There is currently no evidence for any clinical advantage in the use of alternate solutions for static cold storage. Although experimental data from animal models suggest that IPC, ischaemic postconditioning, various pharmacological agents, gene therapy, and machine perfusion decrease IR injury, none of these interventions can be recommended in clinical practice. This is because of the lack of randomized controlled trials assessing the safety and efficacy of ischaemic postconditioning, gene therapy, and machine perfusion. Randomized controlled trials and systematic reviews of randomized controlled trials assessing the safety and efficacy of IPC and various pharmacological agents have demonstrated biochemical or histological improvements but this has not translated to clinical benefit. Further well designed randomized controlled trials are necessary to assess the various new protective strategies in liver resection.
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Therapeutic Metabolic Inhibition: Hydrogen Sulfide Significantly Mitigates Skeletal Muscle Ischemia Reperfusion Injury In Vitro and In Vivo. Plast Reconstr Surg 2010; 126:1890-1898. [DOI: 10.1097/prs.0b013e3181f446bc] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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