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Minimally invasive donor hepatectomy is an emerging surgical technique in living donor liver transplantation (LDLT). We examined outcomes across open, laparoscopic, and robotic LDLT using a prospective registry. We analyzed 3448 cases (1724 donor-recipient pairs) from January 2011 to March 2023 (NCT06062706). Among donors, 520 (30%) were female. Adult-to-adult LDLT comprised 1061 (62%) cases. A total of 646 (37%) of the donors underwent open, 165 (10%) laparoscopic, and 913 (53%) robotic hepatectomies. Primary outcomes: donor overall morbidity was 4% (35/903) for robotic, 8% (13/165) laparoscopic, and 16% (106/646) open (P < .001) procedures. Pediatric and adult recipient mortality was similar among the 3 donor hepatectomy approaches: robotic 1.5% and 7.0%, compared with 2.3% and 8.3% laparoscopic, and 1.6% and 5.5% for open donor surgery, respectively (P = .802, P = .564). Secondary outcomes: pediatric and adult recipients major morbidity after robotic hepatectomy was 15% and 23%, compared with 25% and 44% for laparoscopic surgery and 19% and 31% for open surgery, respectively (P = .033, P < .001). Graft and recipient 5-year survival were 90% and 93% for pediatrics and 79% and 80% for adults, respectively. In conclusion, robotic LDLT was associated with superior outcomes when compared with the laparoscopic and open approaches. Both donors and, for the first time reported, recipients benefitted from lower morbidity rates in robotic surgery, emphasizing its potential for further advancing this field.
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In living-donor liver transplantation, biliary complications including bile leaks and biliary anastomotic strictures remain significant challenges, with incidences varying across different centers. This multicentric retrospective study (2016-2020) included 3633 adult patients from 18 centers and aimed to identify risk factors for these biliary complications and their impact on patient survival. Incidences of bile leaks and biliary strictures were 11.4% and 20.6%, respectively. Key risk factors for bile leaks included multiple bile duct anastomoses (odds ratio, [OR] 1.8), Roux-en-Y hepaticojejunostomy (OR, 1.4), and a history of major abdominal surgery (OR, 1.4). For biliary anastomotic strictures, risk factors were ABO incompatibility (OR, 1.4), blood loss >1 L (OR, 1.4), and previous abdominal surgery (OR, 1.7). Patients experiencing biliary complications had extended hospital stays, increased incidence of major complications, and higher comprehensive complication index scores. The impact on graft survival became evident after accounting for immortal time bias using time-dependent covariate survival analysis. Bile leaks and biliary anastomotic strictures were associated with adjusted hazard ratios of 1.7 and 1.8 for graft survival, respectively. The study underscores the importance of minimizing these risks through careful donor selection and preoperative planning, as biliary complications significantly affect graft survival, despite the availability of effective treatments.
Subject(s)
Graft Survival , Liver Transplantation , Living Donors , Postoperative Complications , Humans , Liver Transplantation/adverse effects , Male , Female , Retrospective Studies , Middle Aged , Adult , Risk Factors , Postoperative Complications/etiology , Follow-Up Studies , Prognosis , Anastomotic Leak/etiology , Biliary Tract Diseases/etiology , Incidence , Survival RateABSTRACT
BACKGROUND AND AIMS: Given the increasing demand of patients requiring liver transplant who are 70 years or older and have may have health conditions, this study aimed to assess the outcomes of Living Donor Liver Transplant (LDLT) recipients, in this age group. METHODS: We conducted an analysis using a prospective registry that included all LDLT recipients from January 2011 to May 2023. Patients into two age groups; 18-69 years and 70 years or older and compared their short- term and long-term outcomes. We considered complications as major if they were Grade ≥3a (Dindo-Clavian). RESULTS: Among 1018 LDLT recipients, 71 (7%) were aged 70 years or older. The rates of post-transplant complications of any severity were comparable between the younger and older age groups (467% vs. 46%, p =0.983), as were the rates of major complications (25% vs. 25%, p =0.995) and in-hospital mortality (6% vs. 7%, p =0.800). The 1-, 3-, and 5-year graft survival rates were 94%, 86%, and 81% in the younger group and 92%, 87%, and 65% in the older group ( p =0.090). Similarly, the overall 1-, 3-, and 5-year recipient survival rates were 90%, 85%, and 86% in the younger group and 88%, 86%, and 65% in the older group ( p =0.100). CONCLUSION: This study suggests that carefully selected elderly patients can undergo LDLT and achieve comparable short-term outcomes to their younger counterparts.
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OBJECTIVE: To define benchmark values for adult-to-adult living-donor liver transplantation (LDLT). BACKGROUND: LDLT utilizes living-donor hemiliver grafts to expand the donor pool and reduce waitlist mortality. Although references have been established for donor hepatectomy, no such information exists for recipients to enable conclusive quality and comparative assessments. METHODS: Patients undergoing LDLT were analyzed in 15 high-volume centers (≥10 cases/year) from 3 continents over 5 years (2016-2020), with a minimum follow-up of 1 year. Benchmark criteria included a Model for End-stage Liver Disease ≤20, no portal vein thrombosis, no previous major abdominal surgery, no renal replacement therapy, no acute liver failure, and no intensive care unit admission. Benchmark cutoffs were derived from the 75th percentile of all centers' medians. RESULTS: Of 3636 patients, 1864 (51%) qualified as benchmark cases. Benchmark cutoffs, including posttransplant dialysis (≤4%), primary nonfunction (≤0.9%), nonanastomotic strictures (≤0.2%), graft loss (≤7.7%), and redo-liver transplantation (LT) (≤3.6%), at 1-year were below the deceased donor LT benchmarks. Bile leak (≤12.4%), hepatic artery thrombosis (≤5.1%), and Comprehensive Complication Index (CCI Ā® ) (≤56) were above the deceased donor LT benchmarks, whereas mortality (≤9.1%) was comparable. The right hemiliver graft, compared with the left, was associated with a lower CCI Ā® score (34 vs 21, P < 0.001). Preservation of the middle hepatic vein with the right hemiliver graft had no impact neither on the recipient nor on the donor outcome. Asian centers outperformed other centers with CCI Ā® score (21 vs 47, P < 0.001), graft loss (3.0% vs 6.5%, P = 0.002), and redo-LT rates (1.0% vs 2.5%, P = 0.029). In contrast, non-benchmark low-volume centers displayed inferior outcomes, such as bile leak (15.2%), hepatic artery thrombosis (15.2%), or redo-LT (6.5%). CONCLUSIONS: Benchmark LDLT offers a valuable alternative to reduce waitlist mortality. Exchange of expertise, public awareness, and centralization policy are, however, mandatory to achieve benchmark outcomes worldwide.
Subject(s)
End Stage Liver Disease , Liver Diseases , Liver Transplantation , Thrombosis , Adult , Humans , Living Donors , Benchmarking , End Stage Liver Disease/surgery , Treatment Outcome , Retrospective Studies , Severity of Illness Index , Liver Diseases/complications , Graft SurvivalABSTRACT
INTRODUCTION: To this day, a discrepancy exists between donor liver demand and supply. Domino liver transplantation (DLT) can contribute to increasing the number of donor livers available for transplantation. METHODS: The design of this systematic review was based on the Preferred Reporting Items for Systematic Reviews (PRISMA). A qualitative analysis of included studies was performed. Primary outcomes were mortality and peri- and postoperative complications related to DLT. RESULTS: Twelve studies met the inclusion criteria. All included studies showed that DLT outcomes were comparable to outcomes of deceased donor liver transplantation (DDLT) in terms of mortality and complications. One-year patient survival rate ranged from 66.7% to 100%. Re-transplantation rate varied from 0 to 12.5%. Most frequent complications were related to biliary (3.7%-37.5%), hepatic artery (1.6%-9.1%), portal vein (12.5-33.3%) and hepatic vein events (1.6%), recurrence of domino donor disease (3.3%-17.4%) and graft rejection (16.7%-37.7%). The quality of the evidence was rated as moderate according to the Newcastle-Ottawa scale (NOS). CONCLUSION: DLT outcomes were similar to DDLT in terms of mortality and complications. Even though DLT will not solve the entire problem of organ shortage, transplant programs should always consider using this tool to maximize the availability of liver grafts.
Subject(s)
Liver Transplantation , Tissue and Organ Procurement , Humans , Living Donors , Liver Transplantation/adverse effects , Hepatic Artery/surgery , Postoperative Complications/etiology , Graft Survival , Treatment Outcome , Retrospective StudiesABSTRACT
An ischemic-type biliary stricture (ITBS) is a common feature after liver transplantation using donation after cardiac death (DCD) grafts. We compared sequential subnormothermic ex vivo liver perfusion (SNEVLP; 33Ā°C) with cold storage (CS) for the prevention of ITBS in DCD liver grafts in pig liver transplantation (n = 5 for each group). Liver grafts were stored for 10 hours at 4Ā°C (CS) or preserved with combined 7-hour CS and 3-hour SNEVLP. Parameters of hepatocyte [aspartate aminotransferase (AST), international normalized ratio (INR), factor V, and caspase 3 immunohistochemistry], endothelial cell (EC; CD31 immunohistochemistry and hyaluronic acid), and biliary injury and function [alkaline phosphatase (ALP), total bilirubin, and bile lactate dehydrogenase (LDH)] were determined. Long-term survival (7 days) after transplantation was similar between the SNEVLP and CS groups (60% versus 40%, P = 0.13). No difference was observed between SNEVLP- and CS-treated animals with respect to the peak of serum INR, factor V, or AST levels within 24 hours. CD31 staining 8 hours after transplantation demonstrated intact EC lining in SNEVLP-treated livers (7.3 Ć 10(-4) Ā± 2.6 Ć 10(-4) cells/Āµm(2)) but not in CS-treated livers (3.7 Ć 10(-4) Ā± 1.3 Ć 10(-4) cells/Āµm(2) , P = 0.03). Posttransplant SNEVLP animals had decreased serum ALP and serum bilirubin levels in comparison with CS animals. In addition, LDH in bile fluid was lower in SNEVLP pigs versus CS pigs (14 Ā± 10 versus 60 Ā± 18 Āµmol/L, P = 0.02). Bile duct histology revealed severe bile duct necrosis in 3 of 5 animals in the CS group but none in the SNEVLP group (P = 0.03). Sequential SNEVLP preservation of DCD grafts reduces bile duct and EC injury after liver transplantation.
Subject(s)
Liver Transplantation , Liver/pathology , Organ Preservation/methods , Reperfusion Injury/prevention & control , Animals , Bile Ducts/pathology , Endothelial Cells , Erythrocytes , Hepatocytes , Liver Function Tests , Male , Perfusion , SwineABSTRACT
BACKGROUND: Over the past 20 y, robotic surgery has entered nearly all surgical disciplines, aiming to improve patient outcomes. Liver transplantation has evolved with these advancements, and fully robotic liver transplants represent the latest innovation in this field. This study reports on the world's first series of fully robotic recipient liver transplants from robotic living donors, comparing them with matched cases from the standard open transplant approach. METHODS: A case-control study was conducted at our center from August to December 2023. Patient selection criteria for robotic recipient liver transplantation included a Model for End-stage Liver Disease score of ≤25, specific anatomical characteristics, and logistics. A propensity score analysis with a 1:4 matching ratio was used. RESULTS: The study analyzed 10 fully robotic living donor and robotic recipient liver transplant pairs with a median donor age of 29 y and a recipient age of 61 y. The main indication for transplantation was nonalcoholic steatohepatitis (6/10). There was 1 robotic to open conversion, and the median operation time was 10 h, with a median hospital stay of 13 d, shorter than the 18 d in the open group. Three recipients experienced a complication, and there was no mortality. CONCLUSIONS: The first-ever series of fully robotic living donor recipient liver transplants showed encouraging initial results with a markedly reduced hospital stay. The ultimate goal is to refine the technique to offer robotic liver transplants to the majority of recipients, overcoming the current selection criteria. Further research and a planned randomized controlled trial will aim to confirm these results.
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BACKGROUND: Living donor liver transplantation (LDLT) is the best option for end-stage liver disease patients. Older potential donors are increasingly requesting donation. This study aims to systematically assess the differences in donor perioperative and postoperative complications, mortality, and quality of life (QoL) between younger and older living liver donors. MATERIALS AND METHODS: Embase, Medline, and Cochrane were searched for studies published between 2002 and 2 June 2023. Donor complications, major complications, biliary complications, mortality, and QoL were systematically reviewed, including meta-analyses. Donors aged >50 years were considered older. The methodological quality of the studies was assessed using the Newcastle-Ottawa quality assessment Scale. RESULTS: The search yielded 8320 studies, of which 17 were included. The risk ratio (RR) for complications in younger donors was 1.08 [0.90-1.31] ( P =0.41). RRs for major complications in younger donors were 0.98 [0.64, 1.48] and 0.89 [0.50, 1.57] using Clavien-Dindo ≥III and ≥IIIb as major complication. RR for biliary complications in younger donors was 1.59 [1.05-2.42] ( P =0.03). Mortality rate in younger donors was 47/13Ā 238 (0.4%) and in older donors 13/989 (1.3%). Physical component summary (PCS) in younger donors was 51.87 and in older donors 51.29. Mental component summary (MCS) in younger donors was 52.93 and in older donors 55.40. CONCLUSION: Older donors do not have a higher complication or mortality rate than younger donors after LDLT. They may have a lower rate of biliary complications. Additionally, older donors have a similar QoL after LDLT. With careful selection, older donors can be included in screening programs for living liver donation to expand the donor pool.
Subject(s)
Liver Transplantation , Living Donors , Postoperative Complications , Quality of Life , Humans , Liver Transplantation/adverse effects , Age Factors , Postoperative Complications/epidemiology , Middle Aged , AgedABSTRACT
Background: Liver transplantation (LT) is a therapeutic option in multiple inherited metabolic diseases (IMDs), including methylmalonic acidemia (MMA), as LT reduces the risk of acute metabolic decompensations and long-term complications associated with these diseases. In certain IMDs, such as maple syrup urine disease (MSUD), domino liver transplant (DLT) is an accepted and safe method which expands the donor pool. However, only one adult case of DLT using an MMA donor liver has been reported; outcome and safety are still unknown and questioned. Case Description: In this case report, we describe our experience with DLT using MMA livers. Two adult MMA patients underwent living donor liver transplant (LDLT); their MMA livers were consecutively transplanted into two patients on the liver transplant waiting list who had limited chance of receiving a liver transplant in the short term due to their low model for end-stage liver disease (MELD) scores. No severe peri- or postoperative complications occurred, however the recipients of the MMA livers biochemically now have mild MMA. Conclusions: DLT using MMA grafts is a feasible strategy to treat end-stage liver disease and expand the donor organ pool. However, the recipient of the MMA domino liver may develop mild MMA which could affect quality of life, and long-term safety remains unclear. Further long-term of outcomes for domino recipients of MMA livers, focusing on quality of life and any metabolic complications of transplantation are needed to better define the risks and benefits.
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INTRODUCTION: Outflow obstruction is a rare but critical vascular complication in liver transplantation, which may lead to graft loss and mortality. We report a case of caval vein outflow obstruction due to retrohepatic compression after living donor liver transplantation (LDLT), which was managed by temporary implantation of a vena cava filter. PRESENTATION OF CASE: A 63-year-old male with end stage liver disease presented with caval vein outflow obstruction and massive ascites 12Ā days after right lobe LDLT. We opted for a minimally invasive approach and implanted a vena cava filter at the compressed site through transjugular route. The patient's ascites drainage significantly decreased and graft function maintained stable after the intervention. On day 50 posttransplant, the filter was successfully removed and the patient was discharged without complications. DISCUSSION: Outflow obstruction after liver transplantation can result from anastomotic stenosis, graft size mismatch, thrombosis or compression of the outflow tract. Various management strategies have been employed both peri- and posttransplant, ranging from surgical interventions to minimally-invasive techniques. The treatment strategy should be tailored to the individual case, considering the timing of presentation and the specific cause for the obstruction. CONCLUSION: We successfully managed a case of compressive outflow obstruction by temporary implantation of a vena cava filter after LDLT. The vena cava filter was safely removed under angiography.
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BACKGROUND: Ischemia of the bile duct is a common feature in liver disease and transplantation, which represents a major cause of morbidity and mortality, especially after liver transplantation. Detailed knowledge of its pathogenesis remains incomplete due to the lack of appropriate inĀ vitro models. METHODS: To recapitulate biliary damage induced by ischemia and reperfusion inĀ vitro, human intrahepatic cholangiocyte organoids (ICOs) were grown at low oxygen levels of 1% up to 72Ā h, followed by re-oxygenation at normal levels. FINDINGS: ICOs stressed by ischemia and subsequent re-oxygenation represented the dynamic change in biliary cell proliferation, upregulation of epithelial-mesenchymal transition (EMT)-associated markers, and the evocation of phase-dependent cell death programs similar to what is described in patients. Clinical-grade alpha-1 antitrypsin was identified as a potent inhibitor of both ischemia-induced apoptosis and necroptosis. INTERPRETATION: These findings demonstrate that ICOs recapitulate ischemic cholangiopathy inĀ vitro and enable drug assessment studies for the discovery of new therapeutics for ischemic cholangiopathies. FUNDING: Dutch Digestive FoundationMLDS D16-26; TKI-LSH (Topconsortium Kennis en Innovatie-Life Sciences & Health) grant RELOAD, EMC-LSH19002; Medical Delta program "Regenerative Medicine 4D"; China Scholarship Council No. 201706230252.
Subject(s)
Bile Ducts , Ischemia , Humans , Ischemia/metabolism , Apoptosis , Epithelial Cells , OrganoidsABSTRACT
BACKGROUND & AIMS: Sinusoidal endothelial cell (SEC) and hepatocyte death are early, TNF-α mediated events in ischemia and reperfusion of the liver (I/Rp). We previously reported that TNF-α induced liver injury is dependent on Fibrinogen like protein 2 (FGL2/Fibroleukin) and showed that FGL2 binding to its receptor, FcĆĀ³RIIB, results in lymphocyte apoptosis. In this study we examine whether I/Rp is induced by specific binding of FGL2 to FcĆĀ³RIIB expressed on SEC. METHODS: Hepatic ischemia and reperfusion was induced in wild type (WT) mice and in mice with deletion or inhibition of FGL2 and FcRIIB. Liver injury was determined by AST release, necrosis and animal death. Apoptosis was evaluated with caspase 3 and TUNEL staining. RESULTS: FGL2 deletion or inhibition resulted in decreased liver injury as determined by a marked reduction in both levels of AST and ALT and hepatocyte necrosis. Caspase 3 staining of SEC (12% vs. 75%) and hepatocytes (12% vs. 45%) as well as TUNEL staining of SEC (13% vs. 60%, p=0.02) and hepatocytes (18% vs. 70%, p=0.03), markers of apoptosis, were lower in Fgl2(-/-) compared to WT mice. In vitro incubation of SEC with FGL2 induced apoptosis of SEC from WT mice, but not FcĆĀ³RIIB(-/-) mice. Deletion of FcĆĀ³RIIB fully protected mice against SEC and hepatocyte death in vivo. Survival of mice deficient in either Fgl2(-/-) (80%) or FcĆĀ³RIIB(-/-) (100%) was markedly increased compared to WT mice (10%) which were subjected to 75min of total hepatic ischemia (p=0.001). CONCLUSIONS: FGL2 binding to the FcĆĀ³RIIB receptor expressed on SEC is a critical event in the initiation of the hepatic reperfusion injury cascade through induction of SEC and hepatocyte death.
Subject(s)
Fibrinogen/physiology , Liver/injuries , Liver/pathology , Reperfusion Injury/pathology , Animals , Apoptosis/physiology , Endothelial Cells/pathology , Endothelial Cells/physiology , Fibrinogen/genetics , Hepatocytes/pathology , Liver/physiopathology , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Receptors, IgG/antagonists & inhibitors , Receptors, IgG/deficiency , Receptors, IgG/genetics , Receptors, IgG/metabolism , Reperfusion Injury/etiology , Reperfusion Injury/physiopathologyABSTRACT
The clinical significance of the right posterior segment (RPS) graft in living donor liver transplantation (LDLT) is unknown because of its limited use and technical concerns. This study aimed to review published studies investigating outcomes of RPS grafts. The systematic literature search was conducted to retrieve data from Embase, Medline Ovid, Web of Science, Cochrane CENTRAL, and Google Scholar. Among the 388 articles, six retrospective studies from Asian countries were included. The overall incidences of major and minor complications after RPS graft procurement were 5.6% and 34.6%, respectively and no donor deaths were reported. RPS graft recipients had the following postoperative complications: overall mortality rate, 14.5%; bile leakage, 8.7%, biliary stenosis, 18.8%, hepatic artery thrombosis, 8.7%, and liver re-transplantation, 2.9%. The RPS graft can be considered as an option for a living liver graft respecting donor safety under strict selection criteria and surgical strategy. The precise evaluation and understanding of anatomical variations and volumetric analyses is critical for selecting donors and planning the surgical strategy in the RPS grafts procurement. The RPS grafts procurement requires carefully dissection of the hepatic artery and portal vein, safely confirmation of the bile duct, and precisely parenchymal transection. However, further experience is needed to clarify the significance of the RPS graft in LDLT. The special technical requirements should limit this donor procedure to centers with a high level of experience in LDLT.
Subject(s)
Allografts/surgery , Bile Ducts/surgery , Liver Transplantation , Liver/surgery , Living Donors , Postoperative Complications/epidemiology , Allografts/anatomy & histology , Humans , Liver/anatomy & histology , Postoperative Complications/mortality , Treatment OutcomeABSTRACT
OBJECTIVES: Our program routinely used fluorodeoxyglucose-positron emission tomography/computed tomography as part of the liver transplant evaluation of patients with hepatocellular carcinoma. The aim of this study was to evaluate the role of this imaging modality in the pretransplant work-up. MATERIALS AND METHODS: This was a retrospective chart review of our liver transplant database from January 2011 to December 2014 for all patients with hepatocellular carcinoma who underwent a liver transplant. Collected data included age, sex, cause of liver disease, imaging modality, fluorodeoxyglucose-positron emission tomography/computed tomography results, explant tissue analysis, type of transplant, and transplant outcome. RESULTS: During the study period, 275 liver transplants were performed. Fifty-three patients had hepatocellular carcinoma; 41 underwent fluorodeoxyglucose-positron emission tomography/computed tomography. Twenty-nine patients underwent living-donor liver transplant, and 12 patients underwent deceased-donor liver transplant. One of the 41 patients with negative FDG-imaging results had no evidence of hepatocellular carcinoma in the explant and was excluded from the study. The patients' average age was 58 years (range, 22-72 y), and 28 patients were men. The cause of liver disease was hepatitis C virus in 24 patients, cryptogenic cirrhosis in 12 patients, and hepatitis B virus in 5 patients. One patient had no hepatocellular carcinoma on explants and was excluded from the study. Twenty-five patients had hepatocellular carcinoma that met the Milan criteria, 7 were within the UCSF (University of California, San Francisco) criteria, and 8 exceeded the UCSF criteria. Of the 40 patients, 11 had positive fluorodeoxyglucose-positron emission tomography/computed tomography results (27.5%) with evidence of hepatocellular carcinoma in the explant; the remaining 29 patients (72.5%) had negative results. The fluorodeoxyglucose-positron emission tomography/computed tomography results were positive in 16% (4 of 21) of patients who met the Milan criteria, 28% (2 of 7) of patients who met the UCSF criteria and 62% (5 of 8) of patients who exceeded the UCSF criteria. CONCLUSIONS: Fluorodeoxyglucose-positron emission tomography/computed tomography has a low degree of use in patients with hepatocellular carcinoma that falls within the Milan criteria and should not be routinely used as part of the liver transplant work-up.
Subject(s)
Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/surgery , Fluorodeoxyglucose F18/administration & dosage , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/surgery , Liver Transplantation , Positron Emission Tomography Computed Tomography , Radiopharmaceuticals/administration & dosage , Adult , Aged , Carcinoma, Hepatocellular/virology , Databases, Factual , Female , Humans , Liver Neoplasms/virology , Liver Transplantation/methods , Living Donors , Male , Middle Aged , Predictive Value of Tests , Reproducibility of Results , Retrospective Studies , Risk Factors , Treatment Outcome , Young AdultABSTRACT
Reperfusion injury is a problem in organ transplantation. Relaxin causes vessel dilation and inhibition of platelet and mast cell activation. The study investigates the protective effect of relaxin on liver tissue against cell damage during organ preservation and reperfusion. Liver transplantation was simulated in a model of isolated perfused rat liver. Relaxin was applicated during reperfusion and/or preservation. To quantify cell damage, we examined the perfusate for malonyldialdehyde (MDA) and myeloperoxidase activity (MPO), and liver tissue underwent immunohistochemical study. Relaxin as an additional substance in preserving/reperfusion solution decreases MPO and MDA levels in the perfusate and immunohistochemical study. Relaxin seems to have a protective effect against cell damage in ischemia and reperfusion injury.
Subject(s)
Liver Transplantation/methods , Liver/drug effects , Models, Animal , Organ Preservation Solutions/chemistry , Organ Preservation/methods , Relaxin/pharmacology , Reperfusion Injury/prevention & control , Animals , Chemotherapy, Cancer, Regional Perfusion , Liver/pathology , Liver/surgery , Male , Malondialdehyde/pharmacology , Rats , Rats, Wistar , Reperfusion , Solutions , TemperatureABSTRACT
BACKGROUND: Thymoglobulin (ATG) and basiliximab induction therapies are used by the majority of centers for pancreas transplantation today. Although both strategies have different mechanisms, there is a paucity of studies comparing them. We compared the efficacy and side effects of both methods in simultaneous pancreas-kidney (SPK) transplantation. METHODS: We analyzed 128 SPKs at our institution between January 2001 and August 2008. Forty-nine patients received basiliximab (40 mg), whereas 79 patients had ATG (5 mg/kg). Graft function, complications, rejection, and survival rates were analyzed. RESULTS: ATG versus basiliximab therapy was associated with decreased 3-month (6% vs. 21%; P=0.01) and 1-year (14% vs. 27%; P=0.049) rejection rate. Steroid-resistant rejections were decreased with ATG (3%) vs. basiliximab (14%) (P=0.01). In a univariate regression analysis, basiliximab induction was a risk factor for rejection (HR, 7.1; CI, 3.8-13). No differences were observed regarding complications and graft function up to 5 years. ATG versus basiliximab therapy resulted in identical 1-year (90% vs. 93%), 3-year (87% vs. 89%), and 5-year (78% vs. 83%) pancreas survival (P=0.7). No difference was observed in kidney survival after 1 year (99% vs. 98%), 3 years (97% vs. 98%), and 5 years (95% vs. 95%) (P=0.4). CONCLUSIONS: ATG versus basiliximab induction therapy results in decreased acute cellular rejection in the first year after SPK with similar side effects. Long-term graft function and survival are not affected by induction regimen.
Subject(s)
Antibodies, Monoclonal/therapeutic use , Antilymphocyte Serum/therapeutic use , Graft Rejection/epidemiology , Graft Survival/physiology , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/immunology , Pancreas Transplantation/immunology , Recombinant Fusion Proteins/therapeutic use , Adult , Antibodies, Monoclonal/adverse effects , Antilymphocyte Serum/adverse effects , Basiliximab , Female , Humans , Immunosuppressive Agents/adverse effects , Kidney Transplantation/mortality , Longitudinal Studies , Male , Pancreas Transplantation/mortality , Recombinant Fusion Proteins/adverse effects , Regression Analysis , Retrospective Studies , Risk Factors , Survival Rate , Treatment OutcomeABSTRACT
Ischemia reperfusion injury (IRI) is a problem in organ transplantation. Relaxin is known to have a protective effect against liver injury caused by IRI. Using a model of isolated perfused rat liver, the local oxygen supply in liver tissue was investigated by spectrophotometric in vivo imaging and compared to the protective effect of relaxin shown by immunohistochemical measurement of myeloperoxidase and malonyldialdehyde activities as determinants of oxidative stress. In relaxin-treated liver tissue, spectrophotometry showed a better oxygen supply and decreased myeloperoxidase and malonyldialdehyde activities. Our data suggest that relaxin can influence the oxygen distribution in liver tissue and reduce cell damage caused by IRI.
Subject(s)
Liver Transplantation , Liver/drug effects , Liver/metabolism , Organ Preservation Solutions/pharmacology , Relaxin/pharmacology , Animals , Male , Malondialdehyde/metabolism , Oxidative Stress/drug effects , Peroxidase/metabolism , Rats , Rats, Wistar , Reperfusion Injury/prevention & control , SpectrophotometryABSTRACT
BACKGROUND: Much effort goes into developing and publishing guidelines which physicians fail to implement. We feel that major discrepancies still exist between theory and reality and that the translational approach to this aspect of medical care has not yet established itself. We therefore decided to investigate in an exemplary audit how liberally inappropriate imaging is used in our emergency department (ED) to rule out acute appendicitis. MATERIAL AND METHODS: Our electronic medical record ED database 'Qualicare' (http://www.qualidoc.ch) was searched using the 'appendicitis' sub data base. The frequency and accuracy of abdominal imaging was determined in patients with clinically suspected appendicitis on admission over a 5-year period at a university hospital emergency unit. RESULTS: In total, 272 (41.2%) of the 577 patients were male and 305 (46.3%) were female. The attending physicians ordered abdominal X-rays in 133 patients, abdominal ultrasounds in 319, and abdominal computerized tomography (CT) scans in 93 patients. 125 patients underwent more than one imaging procedure. In all, 85/125 patients received a combination of X-rays, ultrasound and CT scanning! DISCUSSION: Physicians are often insecure about indications for surgery and therefore order useless imaging procedures. The reliability of such procedures in excluding acute appendicitis is limited, which was confirmed by our results. Although evidence-based medicine guidelines exist, they are neglected for many reasons. Future academic efforts should therefore focus more on knowledge translation and the implementation of existing knowledge by heightening awareness, rather than on simply creating new guidelines.