Dataset Information

Recipient and Donor Outcomes After Living-Donor Liver Transplant for Unresectable Colorectal Liver Metastases.

ABSTRACT:

Importance

Colorectal cancer is a leading cause of cancer-related death, and nearly 70% of patients with this cancer have unresectable colorectal cancer liver metastases (CRLMs). Compared with chemotherapy, liver transplant has been reported to improve survival in patients with CRLMs, but in North America, liver allograft shortages make the use of deceased-donor allografts for this indication problematic.

Objective

To examine survival outcomes of living-donor liver transplant (LDLT) for unresectable, liver-confined CRLMs.

Design, setting, and participants

This prospective cohort study included patients at 3 North American liver transplant centers with established LDLT programs, 2 in the US and 1 in Canada. Patients with liver-confined, unresectable CRLMs who had demonstrated sustained disease control on oncologic therapy met the inclusion criteria for LDLT. Patients included in this study underwent an LDLT between July 2017 and October 2020 and were followed up until May 1, 2021.

Exposures

Living-donor liver transplant.

Main outcomes and measures

Perioperative morbidity and mortality of treated patients and donors, assessed by univariate statistics, and 1.5-year Kaplan-Meier estimates of recurrence-free and overall survival for transplant recipients.

Results

Of 91 evaluated patients, 10 (11%) underwent LDLT (6 [60%] male; median age, 45 years [range, 35-58 years]). Among the 10 living donors, 7 (70%) were male, and the median age was 40.5 years (range, 27-50 years). Kaplan-Meier estimates for recurrence-free and overall survival at 1.5 years after LDLT were 62% and 100%, respectively. Perioperative morbidity for both donors and recipients was consistent with established standards (Clavien-Dindo complications among recipients: 3 [10%] had none, 3 [30%] had grade II, and 4 [40%] had grade III; donors: 5 [50%] had none, 4 [40%] had grade I, and 1 had grade III).

Conclusions and relevance

This study's findings of recurrence-free and overall survival rates suggest that select patients with unresectable, liver-confined CRLMs may benefit from total hepatectomy and LDLT.

SUBMITTER: Hernandez-Alejandro R

PROVIDER: S-EPMC8968681 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Recipient and Donor Outcomes After Living-Donor Liver Transplant for Unresectable Colorectal Liver Metastases.

Hernandez-Alejandro Roberto R Ruffolo Luis I LI Sasaki Kazunari K Tomiyama Koji K Orloff Mark S MS Pineda-Solis Karen K Nair Amit A Errigo Jennie J Dokus M Katherine MK Cattral Mark M McGilvray Ian D ID Ghanekar Anand A Gallinger Steven S Selzner Nazia N Claasen Marco P A W MPAW Burkes Ron R Hashimoto Koji K Fujiki Masato M Quintini Cristiano C Estfan Bassam N BN Kwon Choon Hyuck David CHD Menon K V Narayanan KVN Aucejo Federico F Sapisochin Gonzalo G

JAMA surgery 20220601 6

<h4>Importance</h4>Colorectal cancer is a leading cause of cancer-related death, and nearly 70% of patients with this cancer have unresectable colorectal cancer liver metastases (CRLMs). Compared with chemotherapy, liver transplant has been reported to improve survival in patients with CRLMs, but in North America, liver allograft shortages make the use of deceased-donor allografts for this indication problematic.<h4>Objective</h4>To examine survival outcomes of living-donor liver transplant (LDL ...[more]

PMID: 35353121

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Project description:ImportanceThe proportion of living donor kidney transplants from donors unrelated to their recipients is increasing in the US.ObjectiveTo examine the association between donor-recipient biological relationship and allograft survival after living donor kidney transplant.Design, setting, and participantsThis retrospective cohort study used Organ Procurement and Transplantation Network data on US adult living donor kidney transplants (n = 86 154) performed from January 1, 2000, to December 31, 2014, excluding cases in which recipients previously received a kidney transplant (n = 10 342) or key data were missing (n = 2832). Last follow-up was March 20, 2020.ExposuresDonor-recipient biological relationship.Main outcomes and measuresThe primary outcome was death-censored allograft failure. Univariate and multivariable time-to-event analyses were performed for death-censored allograft failure for the overall cohort, then separately for recipients with and without primary diagnoses of cystic kidney disease and for transplants from African American and non-African American donors.ResultsAmong the 72 980 transplant donor and recipients included in the study (median donor age, 41 years; interquartile range [IQR], 32-50 years; 43 990 [60%] female; 50 014 [69%] White), 43 174 (59%) donors and recipients were biologically related and 29 806 (41%) were unrelated. Donors related to their recipients were younger (median [IQR] age, 39 [31-48] vs 44 [35-52] years) and less likely to be female (24 848 [58%] vs 19 142 [64%]) or White (26 933 [62%] vs 23 081 [77%]). Recipients related to their donors were younger (median [IQR] age, 48 [34-58] vs 50 [40-58] years), more likely to be female (18 035 [42%] vs 10 530 [35%]), and less likely to have cystic kidney disease (2530 [6%] vs 4600 [15%]). Related pairs had fewer HLA mismatches overall (median [IQR], 3 [2-3] vs 5 [4-5]). After adjustment for HLA mismatches, donor and recipient characteristics, and transplant era, donor-recipient biological relationship was associated with higher death-censored allograft failure (hazard ratio, 1.05; 95% CI, 1.01-1.10; P = .03). When stratified by primary disease, this association persisted only for recipients without cystic kidney disease. When stratified by donor race, this association persisted only for transplants from African American donors.Conclusions and relevanceIn this cohort study, living donor kidney transplants from donors biologically related to their recipients had higher rates of allograft failure than transplants from donors unrelated to their recipients after HLA matching was accounted for. Further study is needed to determine which genetic or socioenvironmental factors are associated with this finding.

Project description:ImportanceDespite the acceptance of living-donor liver transplant (LDLT) as a lifesaving procedure for end-stage liver disease, it remains underused in the United States. Quantification of lifetime survival benefit and the Model for End-stage Liver Disease incorporating sodium levels (MELD-Na) score range at which benefit outweighs risk in LDLT is necessary to demonstrate its safety and effectiveness.ObjectiveTo assess the survival benefit, life-years saved, and the MELD-Na score at which that survival benefit was obtained for individuals who received an LDLT compared with that for individuals who remained on the wait list.Design, setting, and participantsThis case-control study was a retrospective, secondary analysis of the Scientific Registry of Transplant Recipients database of 119 275 US liver transplant candidates and recipients from January 1, 2012, to September 2, 2021. Liver transplant candidates aged 18 years or older who were assigned to the wait list (N = 116 455) or received LDLT (N = 2820) were included. Patients listed for retransplant or multiorgan transplant and those with prior kidney or liver transplants were excluded.ExposuresLiving-donor liver transplant vs remaining on the wait list.Main outcomes and measuresThe primary outcome of this study was life-years saved from receiving an LDLT. Secondary outcomes included 1-year relative mortality and risk, time to equal risk, time to equal survival, and the MELD-Na score at which that survival benefit was obtained for individuals who received an LDLT compared with that for individuals who remained on the wait list. MELD-Na score ranges from 6 to 40 and is well correlated with short-term survival. Higher MELD-Na scores (>20) are associated with an increased risk of death.ResultsThe mean (SD) age of the 119 275 study participants was 55.1 (11.2) years, 63% were male, 0.9% were American Indian or Alaska Native, 4.3% were Asian, 8.2% were Black or African American, 15.8% were Hispanic or Latino, 0.2% were Native Hawaiian or Other Pacific Islander, and 70.2% were White. Mortality risk and survival models confirmed a significant survival benefit for patients receiving an LDLT who had a MELD-Na score of 11 or higher (adjusted hazard ratio, 0.64 [95% CI, 0.47-0.88]; P = .006). Living-donor liver transplant recipients gained an additional 13 to 17 life-years compared with patients who never received an LDLT.Conclusions and relevanceAn LDLT is associated with a substantial survival benefit to patients with end-stage liver disease even at MELD-Na scores as low as 11. The findings of this study suggest that the life-years gained are comparable to or greater than those conferred by any other lifesaving procedure or by a deceased-donor liver transplant. This study's findings challenge current perceptions regarding when LDLT survival benefit occurs.

Project description:Rationale & objectiveSome living donor kidneys are found to have biopsy evidence of chronic scarring and/or glomerular disease at implantation, but it is unclear if these biopsy findings help predict donor kidney recovery or allograft outcomes. Our objective was to identify the prevalence of chronic histological changes and glomerular disease in donor kidneys, and their association with donor and recipient outcomes.Study designRetrospective cohort study.Setting & participantsSingle center, living donor kidney transplants from January 2010 to July 2022.ExposureChronic histological changes, glomerular disease in donor kidney implantation biopsies.OutcomeFor donors, single-kidney estimated glomerular filtration rate (eGFR) increase, percent total eGFR loss, ≥40% eGFR decline from predonation baseline, and eGFR<60mL/min/1.73m2 at 6 months after donation; for recipients, death-censored allograft survival.Analytical approachBiopsies were classified as having possible glomerular disease by pathologist diagnosis or chronic changes based on the percentage of glomerulosclerosis, interstitial fibrosis/tubular atrophy, and vascular disease. We used logistic regression to identify factors associated with the presence of chronic changes, linear regression to identify the association between chronic changes and single-kidney estimated glomerular filtration rate (eGFR) recovery, and time-to-event analyses to identify the relationship between abnormal biopsy findings and allograft outcomes.ResultsAmong 1,104 living donor kidneys, 155 (14%) had advanced chronic changes on implantation biopsy, and 12 (1%) had findings suggestive of possible donor glomerular disease. Adjusted logistic regression showed that age (odds ratio [OR], 2.44 per 10 years [95% CI, 1.98-3.01), Hispanic ethnicity (OR, 1.87 [95% CI, 1.15-3.05), and hypertension (OR, 1.92 [95% CI, 1.01-3.64), were associated with higher odds of chronic changes on implantation biopsy. Adjusted linear regression showed no association of advanced chronic changes with single-kidney eGFR increase or relative risk of eGFR<60mL/min/1.73m2. There were no differences in time-to-death-censored allograft failure in unadjusted or adjusted Cox proportional hazards models when comparing kidneys with chronic changes to kidneys without histological abnormalities.LimitationsRetrospective, absence of measured GFR.ConclusionsApproximately 1 in 7 living donor kidneys had chronic changes on implantation biopsy, primarily in the form of moderate vascular disease, and 1% had possible donor glomerular disease. Abnormal implantation biopsy findings were not significantly associated with 6-month donor eGFR outcomes or allograft survival.Plain-language summaryKidney biopsies are the gold standard test to identify the presence or absence of kidney disease. However, kidneys donated by healthy living donors-who are extensively screened for any evidence of kidney disease before donation-occasionally show findings that might be considered "abnormal," including the presence of scarring in the kidney or findings suggestive of a primary kidney disease. We studied the frequency of abnormal kidney biopsy findings among living donors at our center. We found that about 14% of kidneys had chronic abnormalities and 1% had findings suggesting possible glomerular kidney disease, but the presence of abnormal biopsy findings was not associated with worse outcomes for the donors or their recipients.

Project description:BackgroundNephron endowment in renal transplantation is infrequently considered, but may have important implications for post kidney transplantation outcomes. In this population-cohort study, we analyzed the deceased-donor kidney transplant outcomes stratified by donor-to-recipient size ratios.MethodsData for all deceased-donor adult kidney transplantation recipients between 2003 and 2015 were extracted from the UK Transplant Registry. We used weight as a surrogate marker for kidney size and defined the following mismatch categories (donor weight/recipient weight × 100): less than 75% (small donor kidney), 75% to 125% (weight matched kidney), and greater than 125% (large donor kidney). Univariable and multivariable analyses were undertaken to assess the relationship between this marker and patient outcomes.ResultsOutcomes for 11 720 transplants were analyzed with weight mismatch stratified as follows; small donor kidney (n = 1608, 13.7%), weight matched kidney (n = 7247, 61.8%) and large donor kidney (n = 2865, 24.4%). On multivariable analysis, no significant differences were detected in overall (P = 0.876) or death-censored (P = 0.173) graft survival, or in rates of delayed graft function (P = 0.396) between these 3 groups. However, 12-month creatinine levels were found to decline progressively across the groups (P < 0.001), with adjusted averages of 144.2 μmol/L for recipients of small donor kidneys, 134.7 μmol/L in weight matched kidneys, and 124.9 μmol/L in recipients of large donor kidneys. In addition, patient survival was found to be significantly shorter in recipients of larger kidneys than those with weight matched kidneys (hazard ratio, 1.21; 95% confidence interval, 1.05-1.40; P = 0.009), which is inconsistent with the existing literature.ConclusionsOur data demonstrate that 12-month creatinine is influenced by donor-to-recipient difference in body weight, but that no such difference is observed for either delayed graft function or death-censored graft survival. However, we observed increased mortality in recipients receiving larger kidneys; an observation which conflicts with the existing literature and warrants further investigation.

Dataset Information

Recipient and Donor Outcomes After Living-Donor Liver Transplant for Unresectable Colorectal Liver Metastases.

Importance

Objective

Design, setting, and participants

Exposures

Main outcomes and measures

Results

Conclusions and relevance

Publications

Recipient and Donor Outcomes After Living-Donor Liver Transplant for Unresectable Colorectal Liver Metastases.

Similar Datasets

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