Toshihiro Nakayama
Visiting Instructor/Lecturer, Surgery - Abdominal Transplantation
Honors & Awards
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Poster of Distinction, The Liver Meeting (2025)
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Overseas Fellowship Grant, Uehara Memorial Foundation (2024)
Professional Education
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MD, The University of Tokyo School of Medicine (2020)
Contact
https://orcid.org/0000-0001-8216-0371All Publications
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Donor-Recipient Age Mismatch and Long-Term Graft Outcomes After Adolescent Liver Transplant.
JAMA network open
2026; 9 (1): e2552779
Abstract
Importance: Donor-recipient age mismatch is an established risk factor in adult liver transplants (LTs), yet its effect in adolescents, who require long-term graft durability, has not been fully characterized. Despite pediatric prioritization, some adolescent donor livers are allocated to adults, limiting access to age-matched grafts for adolescents.Objective: To assess whether a donor-recipient age difference of 10 or more years is associated with inferior graft survival in LTs among adolescents and to estimate the benefits of broader geographic sharing of adolescent donor livers.Design, Setting, and Participants: This retrospective, registry-based case-control study used data from the Organ Procurement & Transplantation Network database, a nationwide US transplant registry. Participants were adolescents aged 12 to 17 years who received liver-only grafts from donation after brain death between March 1, 2002, and December 31, 2024, with follow-up until April 4, 2025. Propensity score matching (1:1) was performed on graft type and size mismatch, donor sex, donor-recipient sex mismatch, transplant center volume, and recipient variables.Exposure: Donor-recipient age difference of 10 or more years (age-mismatched graft) vs less than 10 years (age-matched graft).Main Outcomes and Measures: The primary outcome was 10-year graft survival. The secondary outcome was 10-year overall survival. Waiting time to an age-matched graft offer under alternative donor-sharing radii (1500 nautical miles [NM], 1000 NM, or no limit vs 500 NM) were also estimated.Results: Among 2020 adolescents receiving LTs (median age, 15.0 [IQR, 13.0-16.0] years; 1081 [53.5%] female), 612 (30.3%) received age-mismatched grafts (median donor age, 36.0 [IQR, 29.0-45.0] years) and 1408 (69.7%) received age-matched grafts (median donor age, 16.0 [IQR, 13.0-17.0] years). The age-mismatched group had a higher proportion of recipient candidates in the intensive care unit at transplant (287 [46.9%] vs 250 [17.8%]; P<.001). After propensity score matching (n=526 per group), 10-year graft survival was 61.5% in the age-mismatched group and 74.2% in the age-matched group (P<.001), with consistent results across recipients' pretransplant hospitalization status. A simulation estimated that expanding the adolescent allocation radius to 1000 NM would allow 90% of adolescent candidates to receive age-matched offers within 15 days, compared with 44 days under the current 500-NM limit.Conclusions and Relevance: In this case-control study of a US national cohort of adolescents receiving LT, donor-recipient age mismatch of 10 or more years was associated with inferior graft survival. Broader allocation of adolescent donors may improve access to age-matched grafts and long-term outcomes.
View details for DOI 10.1001/jamanetworkopen.2025.52779
View details for PubMedID 41499116
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Renal Resistance on Hypothermic Machine Perfusion and Acceptance of Deceased Donor Kidney Allografts.
Journal of the American Society of Nephrology : JASN
2025
View details for DOI 10.1681/ASN.0000000986
View details for PubMedID 41563235
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Survival Benefit of Accepting Livers From Donation After Circulatory Death Donors Older Than or Equal to 60 y in the United States.
Transplantation
2025
Abstract
Since the approval by the Food and Drug Administration of normothermic machine perfusion in September 2021, the utilization of donation after circulatory death (DCD) livers has significantly increased in the United States. Despite these advancements, acceptance of DCD livers from donors aged 60 y or older (DCD60) varies significantly among transplant centers.This study analyzed data from the United Network for Organ Sharing database, encompassing 29 327 adult liver transplant candidates offered DCD60 grafts between October 2016 and June 2024. Among these, 704 offers were accepted, and 29 074 candidates received at least 1 DCD60 offer that was ultimately declined. Three-year intention-to-treat survival was measured from accept or decline until waitlist dropout or posttransplant death.At 3 y after initial decline of DCD60 livers, 53.8% received a transplant, 15.1% dropped off the waitlist, and 19.7% were removed for other reasons. Candidates who accepted DCD60 livers had significantly better 3-y intention-to-treat survival compared with those who declined (86.6% versus 74.9%, P < 0.001). In subgroup analyses, the survival benefit was significant for recipients older than 50 y and those with Model for End-Stage Liver Disease (MELD) scores ≥15 when the MELD score increased by 0 to 4 from listing to offer.Accepting DCD60 livers provides a clear survival benefit for appropriately selected candidates, and donor-recipient matching based on age and MELD score is crucial.
View details for DOI 10.1097/TP.0000000000005584
View details for PubMedID 41261396
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Listing for blood type A2 donors is highly variable and impacts waitlist outcomes among blood type O liver transplantation candidates in the United States.
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
2025
Abstract
Blood type O liver transplantation (LT) candidates in the United States face the highest waitlist mortality due to the broader compatibility of type O grafts. Although blood-type compatible transplant is a gold standard, type O candidates might benefit from listing for A2 donors, whose antigen is known for its decreased immunogenicity. This study examines the trends and impact on waitlist outcomes of listing for A2 donors among 67,756 type O LT candidates listed between 2010 and 2023 using data from the United Network for Organ Sharing database. The number of A2-to-O LTs increased steadily, with 117 LTs performed in 2023. 61.1% of type O candidates were listed for A2 donors, with considerable regional variations. Fine-Gray competing risk analysis revealed that listing for A2 donors was associated with reduced waitlist dropout rates (subdistribution hazard: 0.94, P < 0.001) and increased transplant probabilities (subdistribution hazard: 1.07, P < 0.001), especially in regions with longer wait times, among candidates with listing Model for End-Stage Liver Disease (MELD)-Na scores between 15 and 34, and candidates listed after the Acuity Circles policy implementation. These findings suggest listing for A2 donors should be encouraged to improve waitlist outcomes for type O candidates.
View details for DOI 10.1016/j.ajt.2025.03.012
View details for PubMedID 40096944
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Potential Double Counting in Meta-Analysis of Combined Heart-liver Transplantation.
Transplantation
2026
View details for DOI 10.1097/TP.0000000000005642
View details for PubMedID 41604423
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Development and validation of a machine-learning model to reduce futile procurements in donations after circulatory death in liver transplantation in the USA: a multicentre study.
The Lancet. Digital health
2025: 100918
Abstract
The number of liver transplants from donors after the circulatory determination of death continues to increase, helping to alleviate the existing organ shortage. However, the rate of attempted but subsequently terminated procurements, known as futile procurements, remains high-mainly because many potential donors do not progress to death within a timeframe after extubation that maintains the suitability of the organ for donation. Futile procurements pose considerable financial and workload burdens to the transplant system. We aimed to develop and validate a machine-learning model to better predict progression to death and reduce futile procurements in cases of donation after circulatory death (DCD).This study included data from 2221 donors from six centres in the USA. Using a retrospective dataset obtained from 1616 donors between December 1, 2022, and June 30, 2023, we developed a prediction model using the Light Gradient Boosting Machine (LightGBM) framework, with neurological, biochemical, respiratory, and circulatory parameters as predictors. The model was validated retrospectively with data from 398 donors (July 1-Aug 31, 2023) and prospectively with data from 207 donors (March 1-Sept 30, 2024). The performance of the model was evaluated through the area under the receiver operating characteristic curve (AUC), accuracy, futile procurement rate, and missed opportunity rate. We also compared the performance of the model with that of two existing risk-prediction tools (the DCD-N score and the Colorado Calculator) and surgeon predictions.Of the 2221 DCD donors in this study, 1260 progressed to death, 927 of whom died within 30 min after extubation. Cross-validation of the LightGBM model yielded AUCs for predicting donor progression to death of 0·833 (95% CI 0·798-0·868) at 30 min, 0·801 (0·767-0·834) at 45 min, and 0·805 (0·770-0·841) at 60 min after extubation. This performance was maintained in both retrospective (0·834 [0·772-0·891], 0·819 [0·757-0·870], and 0·799 [0·737-0·855]) and prospective (0·831 [0·768-0·885], 0·812 [0·749-0·874], and 0·805 [0·740-0·868]) validation cohorts. Compared with surgeon predictions, the LightGBM model had lower futile procurement rates (0·195 vs 0·078, respectively), higher accuracy in cases of poor intersurgeon agreement (0·08 vs 0·29) at 30 min, and similar missed opportunity rates (0·155 vs 0·167). By contrast, the DCD-N score had AUCs of 0·799 (95% CI 0·730-0·860) at 30 min, 0·760 (0·695-0·824) at 45 min, and 0·739 (0·668-0·801) at 60 min, and the Colorado Calculator had AUCs of 0·694 (0·616-0·768), 0·669 (0·596-0·742), and 0·663 (0·585-0·736) at the same timepoints.We show that, compared with surgeon predictions and existing risk-prediction tools, our machine-learning model can enhance the accuracy of the prediction of progression to death in DCD donors and reduce futile procurements. Such improvements have the potential to alleviate some of the financial and operational burdens on the transplant community. Further improvements are needed to decrease missed opportunities and improve the overall accuracy of such models.None.
View details for DOI 10.1016/j.landig.2025.100918
View details for PubMedID 41238506
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Embracing Liver Transplantation From Donation After Circulatory Death in the United States in the Era of Perfusion Technology.
Transplantation
2025
Abstract
Utilization rates of potential deceased donors for liver transplantation has declined following the implementation of the acuity circles system in 2020. Since then, ex situ machine perfusion (es-MP) and normothermic regional perfusion (NRP) have been introduced in the United States.Liver graft utilization rates were analyzed using the US national registry data from 2022 to 2024. The associations of es-MP and NRP practices with donation after circulatory death (DCD) utilization rates among organ procurement organizations (OPOs) and transplant center volume were evaluated.DCD donor utilization significantly increased from 21.5% in 2022 to 42.5% in 2024 (P < 0.001). Utilization of extended criteria donors (ECDs), including DCD donors aged ≥60 y or with a body mass index ≥40 kg/m2, also rose substantially, from 7.1% in 2022 to 33.2% in 2024 (P < 0.001). At the transplant center level, a significant correlation was found between the increase in transplant volume and both the es-MP use (r = 0.29; P = 0.01) and ECD utilization (r = 0.26; P = 0.02). At the OPO level, a significant association was observed between the increase in DCD utilization rate and NRP use (r = 0.29; P = 0.03).DCD liver utilization has significantly increased, with a notable rise in the utilization of ECDs, which may be driven by new technologies such as es-MP and NRP. While es-MP at the center level use may increase transplant volume, NRP use at the OPO level appears to significantly improve DCD liver utilization.
View details for DOI 10.1097/TP.0000000000005537
View details for PubMedID 41088507
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Optimizing liver transplant outcomes for colorectal liver metastases in the united states.
Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society
2025
Abstract
The TransMet trial and Norwegian studies have shown excellent outcomes in highly selected patients undergoing liver transplant (LT) for unresectable colorectal liver metastases (uCRLM). Our aim is to provide an updated analysis of the current state of LT for uCRLM in the US. Adult patients with diagnosis of uCRLM listed for LT between December 2017 and March 2025 were identified from the United Network for Organ Sharing database and analyzed. An analysis between living donor LT (LDLT) and deceased donor LT (DDLT) was performed. During this period, 222 patients were listed, and 158 received a LT across 33 centers. Of these, 76 (48.1%) underwent LDLT, and 82 patients (51.9%) DDLT. Of the 82 deceased donors, 56 (68.2%) were out-of-sequence offers. Overall, the 3-year survival and disease-free survival rates were 66.7%, and 44.0%, respectively. The 3-year survival for LDLT and DDLT was 74.1% and 57.3% (P=0.04), respectively. While these results have not yet reached the acceptable threshold established for other LT indications, these have improved and are expected to continue improving after the implementation of prioritization points. Given the potential variability of oncologic selection criteria and graft quality, we call for the standardization of nationally accepted selection criteria for listing patients for LT with uCRLM and for providing early access with high-quality organs. To achieve this it is imperative to create, or update and maintain national databases that allow for the collection of more granular oncological variables.
View details for DOI 10.1097/LVT.0000000000000746
View details for PubMedID 41086433
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Complications and Status Upgrades among Adult Heart Transplant Candidates with Durable LVADs: Waiting 6 to 8 Years for Status Escalation Is Too Long.
medRxiv : the preprint server for health sciences
2025
Abstract
Introduction: After the 2018 allocation policy change, the rate of listings and transplants with durable LVADs has decreased significantly in favor of bridging patients from temporary mechanical circulatory support to heart transplant. The Organ Procurement and Transplantation Network (OPTN) recently approved a policy, to be implemented in September 2026, stipulating that patients supported by durable LVADs for 6 and 8 years will obtain statuses 3 and 2, respectively.Methods: Using OPTN data, we identified all adult heart transplant candidates with a durable LVAD implanted between October 18, 2018 and May 31, 2025. We estimated the cumulative incidence of status upgrades and durable LVAD-related complications, treating transplantation and waitlist removal before experiencing complications as competing events. We also assessed how the composition of the adult heart transplant waitlist on June 1, 2025 would have changed based on the upcoming policy change.Results: During the study period, 3,881 adult patients were listed for heart transplant with a durable LVAD. 3,182 (82.0%) of the durable LVADs were Abbott HeartMate 3, 568 (14.6%) were Medtronic Heartware HVAD, and 91 (2.3%) were Abbott HeartMate II. Transplant centers submitted a total of 6,924 justifications for status upgrades due to LVAD-related complications (6.3% status 1, 34.3% status 2, and 59.4% status 3) for 1,500 (38.6%) of these patients, with a median of 3 per patient. The cumulative incidence of complications or status upgrades was 38.6% [95% CI (37.1%, 40.2%)]. Nearly all of the 2,381 patients who did not experience any complication or status upgrade during listing were removed from the waitlist by 6 years. Had the upcoming OPTN policy change been implemented on June 1, 2025, the proportion of the waitlist that would have achieved higher priority status instantaneously was 0.06%.Conclusions: The cumulative incidence of status upgrades and complications among heart transplant candidates with durable LVADs was nearly 40% within 6 years of device implantation. The upcoming OPTN policy to escalate patients to statuses 3 and 2 after 6 and 8 years of durable LVAD support, respectively, is unlikely to make a meaningful impact on waitlist priority status.
View details for DOI 10.1101/2025.09.22.25336215
View details for PubMedID 41040709
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AGE MATCHING IMPROVES GRAFT SURVIVAL IN ADOLESCENT LIVER TRANSPLANTATION
WILEY. 2025
View details for Web of Science ID 001606152800161
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High Rate of Transplantation Prior to Review of Status Exception Requests among Adult Heart Transplant Candidates.
medRxiv : the preprint server for health sciences
2025
Abstract
In the United States heart allocation system, when transplant centers submit applications for status exceptions to increase waitlist priority, patients obtain the requested status upgrades immediately while their applications are sent to the regional review boards (RRBs) and reviewed retrospectively. How much time elapses between obtaining a status upgrade through exception and application receipt by the RRBs and how often transplants occur during this period is unknown.Using the Scientific Registry of Transplant Recipients (SRTR), we identified all adult heart transplant candidates listed between October 18, 2018 and December 31, 2023 with submitted applications for status exceptions. We assessed 1) the amount of time elapsed between submission of exception applications and their receipt by the RRBs and 2) the rate of heart transplantation during this "travel" time, stratified by whether the applications were eventually approved or denied. Additionally, using complete match run data, we estimated how many listed patients were skipped by candidates who received transplants with exceptions that were ultimately denied.135 transplant centers submitted status exception requests on behalf of 8,269 adult candidates during the study period, of whom 608 (7.4%) received a denial at least once. The median time from obtaining higher priority statuses immediately via exceptions to application receipt by the RRBs was 3 days. 2,087 out of 8,269 (25.2%) patients received transplants before the RRBs even received their applications, with 115 (18.9%) among 608 with eventual denials and 1,972 (25.7%) among 7,661 with approvals. The cumulative incidence of heart transplantation before application receipt for eventual denials was 19.1% (95% CI [16.0%, 22.3%]) and that for approvals was 26.2% (95% CI [25.2%, 27.1%]) (p < 0.001) at 2 weeks. Based on match run data, the 115 patients who received transplants with denied exceptions bypassed more than seven thousand potential transplant recipients.More than 25% of patients with status exception requests receive heart transplants before their applications are even received by their respective RRBs, let alone reviewed. This raises significant concerns about the efficacy and fairness of retrospective review of exception requests for the allocation of valuable donor hearts.
View details for DOI 10.1101/2025.09.12.25335606
View details for PubMedID 41001456
View details for PubMedCentralID PMC12458605
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FIB-3 index as a novel age-independent predictor of liver fibrosis and prognosis in hepatocellular carcinoma patients undergoing hepatectomy.
Annals of gastroenterological surgery
2025; 9 (5): 1055-1065
Abstract
Liver fibrosis is a key factor in the progression of chronic liver diseases, including viral hepatitis and metabolic dysfunction-associated steatotic liver disease. If untreated, fibrosis can progress to cirrhosis, increasing the risk of liver cancer or failure. This study evaluates the Fibrosis (FIB)-3 index, a novel marker free from age-related biases, for predicting liver fibrosis and 5-year outcomes in hepatocellular carcinoma (HCC) patients undergoing hepatectomy.Data from 1013 patients who underwent liver resection were analyzed in this multi-institutional study. The predictive performance of the FIB-3 index was compared with the original FIB-4 index, which incorporates age into its calculation.The FIB-3 index demonstrated superior accuracy for advanced fibrosis (≥F3) in elderly patients. A higher FIB-3 index was an independent risk factor for recurrence-free survival in elderly patients, underscoring its utility in this population. Notably, the application of appropriate cutoff values allowed the FIB-3 index to facilitate effective risk stratification for 5-year overall survival and recurrence-free survival.The FIB-3 index served as an effective alternative to the FIB-4 index in assessing liver fibrosis among aged patients, and it effectively stratified the likelihood of the 5-year outcomes when utilized in conjunction with a specific cut-off after initial hepatectomy for HCC.
View details for DOI 10.1002/ags3.70010
View details for PubMedID 40922911
View details for PubMedCentralID PMC12414608
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Liver transplantation for unresectable colorectal liver metastases: a narrative review.
Chinese clinical oncology
2025; 14 (4): 44
Abstract
Liver transplantation (LT) for unresectable colorectal liver metastases (uCRLM) initially showed no clear survival advantage in early attempts, leading to waning enthusiasm. Interest was revived in 2013 following the prospective, non-randomized Norwegian Secondary Cancer (SECA) I study, which reported a 5-year overall survival (OS) of 60%-far surpassing outcomes with systemic therapy alone. More recently, the TransMet randomized controlled trial demonstrated a 5-year OS of 73% in the LT-plus-chemotherapy arm vs. 9% with chemotherapy alone, a result comparable to outcomes for established LT indications. This review aims to summarize recent advances and discuss key considerations for implementing LT for uCRLM in clinical practice-particularly patient selection and standardization of protocols.In this narrative review of currently available reports on the outcomes of LT for uCRLM, we identified eight studies [2017-2025] from European and North American centers.Four were prospective (including one randomized trial) and three were multicenter. Their protocols varied considerably, especially regarding donor sources (living vs. deceased) and inclusion criteria for factors such as primary tumor laterality, kirsten rat sarcoma viral oncogene homolog (KRAS) mutation status, and metabolic tumor volume. Overall, 3-year OS ranged from 62% to 100%. Recurrence-free survival (RFS) also showed wide variability, with 3-year RFS between 38% and 68.6%. Centers that employed consistent selection protocols typically reported better survival outcomes, underscoring the importance of standardization. Donor availability emerged as a key factor, with living donor LT offering an alternative in regions where deceased donor access is limited-such as North America and parts of Asia. Extended observation periods and stratification by KRAS status or tumor location (right- vs. left-sided) might help refine patient selection.Although LT for uCRLM is no longer considered purely exploratory, questions remain about the best use of adjuvant chemotherapy. Moving forward, multicenter collaborations, standardized protocols, incorporation of tumor biology insights from resectable CRLM literature, and decision-support strategies (including artificial intelligence) may help optimize patient selection and improve outcomes in this advancing field.
View details for DOI 10.21037/cco-25-46
View details for PubMedID 40897299
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Re-emergence of Early Liver Transplant Access for Hepatocellular Carcinoma in the Era of Normothermic Machine Perfusion.
Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract
2025: 102142
Abstract
Since the FDA approval of normothermic machine perfusion (NMP) in September 2021, liver transplantation (LT) numbers dramatically increased with shortened waitlist times. This is generally a positive trend; however, this might allow hepatocellular carcinoma (HCC) candidates in the United States to receive LT without exception scores, for whom expedited transplant might not be ultimately beneficial. The objective of this study was to describe early transplant access and waitlist outcomes for HCC candidates during the era following FDA approval of NMP.Using the United Network for Organ Sharing (UNOS) database (2016-2023), 15,395 adult candidates listed for LT with HCC exceptions were divided into three listing periods: January 1, 2016 to May 18, 2019 (Delay and Cap), May 19, 2019 to September 27, 2021 (median MELD at transplant minus 3 [MMaT-3]), and September 28, 2021 to December 31, 2023 (NMP). Waitlist outcomes including LT or dropout were assessed using competing risk analysis.Transplant incidence within six months was 16.9% during the NMP era, versus <12% in earlier eras (P<0.001), thanks to aggressive use of extended criteria donors. Significant disparity in LT access among UNOS regions was observed. One-year graft survival after LT remained high, exceeding 90.0% across all eras (P = 0.85).The NMP era demonstrates increased access to LT for HCC candidates in the initial six months prior to qualifying for exception scores.The datasets generated and analyzed during the current study are available from the corresponding author upon reasonable request.
View details for DOI 10.1016/j.gassur.2025.102142
View details for PubMedID 40639609
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Erratum to "Cluster analysis of hepatocellular carcinoma prognosis using preoperative alpha-fetoprotein and des-gamma-carboxy prothrombin levels: a multi-institutional study". [J Gastrointest Surg. 29 (2025) 101980].
Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract
2025: 102129
View details for DOI 10.1016/j.gassur.2025.102129
View details for PubMedID 40545155
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Primary tumor location and KRAS mutation: key prognostic factors in surgically treated colorectal liver metastases.
Hepatobiliary surgery and nutrition
2025; 14 (3): 502-505
View details for DOI 10.21037/hbsn-2025-209
View details for PubMedID 40529931
View details for PubMedCentralID PMC12170000
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Liver-Directed Therapies in Colorectal Cancer: Old Hats and New Tricks.
American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting
2025; 45 (3): e473598
Abstract
Resection of liver metastases is considered the only treatment with curative potential for patients with metastatic colorectal cancer to the liver (CRLM). However, only a minority of patients with CRLM are eligible for up-front resection of liver metastases. Despite advances in systemic chemotherapy, long-term survival is rare without resection of liver metastases. This highlights the unmet need for alternative localized treatment options for patients with unresectable colorectal liver metastases (uCRLM). Liver-directed therapies include hepatic artery infusion pump (HAIP) therapy and nonsurgical locoregional approaches including image-guided ablation, Y90 radioembolization (TARE), and stereotactic body radiation therapy. More recently, emergent data support the use of liver transplantation (LT) in select patients with uCRLM. In this chapter, we review the data for various liver-directed therapies revolutionizing the treatment approach and improving clinical outcomes for patients with uCRLM.
View details for DOI 10.1200/EDBK-25-473598
View details for PubMedID 40505074
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Primary tumor location and KRAS mutation: key prognostic factors in surgically treated colorectal liver metastases
HEPATOBILIARY SURGERY AND NUTRITION
2025
View details for DOI 10.21037/hbsn-2025-209
View details for Web of Science ID 001496057200001
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Out of Sequence Allocation in Liver Transplantation: A Poorly Used Tool to Improve Organ Utilization.
Annals of surgery
2025
Abstract
We evaluated the impact of OOS on organ utilization and also what factors impact the decision to employ OOS.Deceased donor liver allocation typically follows a ranked match-run of potential recipients. Organ procurement organizations (OPOs) may deviate from liver transplant standardized allocation using "out-of-sequence" (OOS) matches.All eligible donors from the Scientific Registry of Transplant Recipients (SRTR) (1/1/2013-8/31/2023) were identified and merged with associated match-runs in the Potential Transplant Recipient (PTR) data. OOS offers were defined as bypass codes (861-863; 760-765). Hierarchical mixed-effects models with eligible donors nested in OPOs assessed OOS-practices versus organ utilization, controlling for liver graft risk with the Discard Risk Index (DSRI) by risk quintile, blood type, and year.OOS were more common each progressive year. Neither TC's (R2<0.01) nor OPO's (R2<0.01) OOS-rate correlated with increased utilization. OOS was not associated with improved utilization (OR=1.11, 95%CI=0.90-1.38). Increasing graft risk in DBD&DCD grafts was associated with reduced utilization. Introducing OOS-allocation interaction terms improved utilization for DCD's of all risk levels but only improved utilization for DSRI 5th-Quintile DBD's. 38% of utilization was explained by graft factors versus 5% by TC-&OPO-variability (Conditional-R2=0.431, Marginal-R2=0.380). High-risk DCD grafts in DSRI 3rd-5th-Quintiles were not more likely to be allocated through OOS despite these grafts demonstrating improved utilization with this approach. Only 15% of variation in OOS-allocation was explained by graft factors versus 23% by TC-and OPO-variability (Conditional R2=0.388, Marginal R2=0.154).OOS improves utilization in high-risk grafts, but graft risk is not correlated with their actual use. This highlights utility in OOS, but also that this practice is currently incorrectly used.
View details for DOI 10.1097/SLA.0000000000006738
View details for PubMedID 40255174
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FIB-3 index as a novel age-independent predictor of liver fibrosis and prognosis in hepatocellular carcinoma patients undergoing hepatectomy
ANNALS OF GASTROENTEROLOGICAL SURGERY
2025
View details for DOI 10.1002/ags3.70010
View details for Web of Science ID 001465384900001
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Graft-to-recipient weight ratio: a timeless standard still shaping outcomes.
Hepatobiliary surgery and nutrition
2025; 14 (2): 295-297
View details for DOI 10.21037/hbsn-2024-766
View details for PubMedID 40342786
View details for PubMedCentralID PMC12057494
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Pathological complete response after chemotherapy in initially unresectable distal cholangiocarcinoma.
Clinical journal of gastroenterology
2025; 18 (2): 357-362
Abstract
Surgical resection is the only curative treatment for cholangiocarcinoma, but it is often diagnosed at advanced stages, making surgical resection infeasible. Recently, the concept of conversion surgery has expanded the indications for surgical treatment, thanks to advancements in both perioperative management and chemotherapy. However, it remains unclear which patients benefit most from this treatment strategy. We present a case of initially unresectable cholangiocarcinoma in which a pathologic complete response was achieved following chemotherapy. A man in his seventies presented with jaundice and was referred to our hospital. Abdominal computed tomography revealed dilation of the intrahepatic bile ducts and thickening of the common bile duct, suggestive of distal cholangiocarcinoma. The tumor was initially unresectable due to metastatic para-aortic lymph nodes, and chemotherapy with gemcitabine and cisplatin was initiated. After six courses of chemotherapy, the lymph nodes showed a partial response, and tumor markers returned to normal levels. However, further chemotherapy was intolerable due to thrombocytopenia. Our cancer board then decided to perform a pancreaticoduodenectomy. Pathologic examination of the resected specimen showed complete disappearance of the primary tumor, but viable cancer cells were found in the resected lymph nodes. Seven months post-surgery, recurrence in the para-aortic nodes was detected through imaging and elevated tumor markers. Despite this, the patient remains alive 16 months post-surgery with normal tumor marker levels, following additional chemotherapy. Pathologic complete response of the primary tumor is rarely observed in patients with initially unresectable distal cholangiocarcinoma, and a multidisciplinary approach, including conversion surgery, may be effective in such cases.
View details for DOI 10.1007/s12328-024-02084-w
View details for PubMedID 39731697
View details for PubMedCentralID PMC11922966
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Mixed neuroendocrine-non-neuroendocrine neoplasm of the colon treated with laparoscopic resection and adjuvant chemotherapy: a case report.
Clinical journal of gastroenterology
2025; 18 (2): 314-323
Abstract
Mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) of the colon is rare with a poor prognosis. Since the first description of a mixed neoplasm 100 years ago, the nomenclature has evolved, most recently with the 2022 World Health Organization (WHO) classification system. We describe our experience of a case of locoregionally advanced MiNEN of the descending colon treated with curative laparoscopic resection and adjuvant chemotherapy. The patient is a 72 year old woman who presented with haematochezia. Initial clinical diagnosis was poorly differentiated adenocarcinoma of the descending colon, cT2N0M0, cStage I. Laparoscopic partial colectomy of the descending colon with D3 lymph node dissection and intracorporeal overlap anastomosis was performed. The pathological diagnosis however, returned mixed adenocarcinoma-neuroendocrine carcinoma (MANEC) of the descending colon, pT4aN1bM0, pStage IIIB, a subgroup of MiNEN: 70% was neuroendocrine carcinoma (NEC), whilst poorly differentiated mucinous carcinoma constituted 30% of the tumour. She completed 4 courses of irinotecan plus cisplatin (IP) adjuvant chemotherapy and is currently recurrence-free at postoperative year 2. The clinical course of MiNEN depends on the biology of the two components, both of which must be pathologically characterised. Even quantitatively discrete components should be carefully subtyped as their prognostic relevance is undetermined.
View details for DOI 10.1007/s12328-024-02089-5
View details for PubMedID 39799545
View details for PubMedCentralID 3712682
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Geospatial analysis of liver donation after death by drug intoxication.
Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society
2025
Abstract
Increases in deaths from drug intoxication in the United States could be contributing to more liver donations. This study investigates regional variation in liver donation following death by drug intoxication over a decade.The number of drug intoxication-related deaths in the continental United States (2011-2020) was collected from CDC WONDER. Reports from UNOS provided the number of liver donors who died of drug intoxication over the decade. County-level ratios of liver donors after drug intoxication to the total number of drug intoxication-related deaths were calculated. Missed donation opportunities were quantified by comparing the actual number of donors to the hypothetical number if all counties achieved the efficiency of counties in the 90th and 50th percentiles. Regression analysis was used to assess the relationship between missed opportunities for liver donation per drug intoxication-related death and county-level variables.County-level proportions of liver donors after drug intoxication to all eligible drug intoxications ranged from 0 to 0.600. If every county matched the efficiency of the 90th and 50th percentile county, the liver donor pool could grow by 7572 or 1550 donors over the decade, respectively. The national rate of missed opportunities for liver donation per death by drug intoxication was 0.114 or 0.022 depending on whether the 90th or 50th percentile donation ratio was used in calculation. The number of missed donations per drug intoxication increased with higher social vulnerability, distance from a trauma center, and rural county status. Conversely, it decreased as the rate of deaths by drug intoxication rose.Assessing liver donation following drug intoxication allows for targeted efforts to increase donations in regions with the greatest potential for improvement.
View details for DOI 10.1097/LVT.0000000000000618
View details for PubMedID 40167364
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Time to Expand Selection Criteria for MELD Exception Points in Liver Transplantation for Hepatocellular Carcinoma.
Transplantation
2025
View details for DOI 10.1097/TP.0000000000005396
View details for PubMedID 40128166
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Exploring the Viability of Matching Marginal Donors With Low Renal Function Recipients in Liver Transplantation.
Clinical transplantation
2025; 39 (3): e70123
Abstract
BACKGROUND: Renal function varies among liver transplantation (LT) candidates with the same Model for End-Stage Liver Disease (MELD)3.0 score. The impact of marginal grafts on post-LT renal function and prognosis varies based on the pre-LT renal function. We explored the effects of matching recipients with low renal function to marginal donors on graft survival (GS) and post-LT kidney function.METHODS: We analyzed data from the Scientific Registry of Transplant Recipients (SRTR), categorizing pre-LT renal function by estimated glomerular filtration rate (eGFR) into low (<30mL/min/1.73m2) and high (≥30mL/min/1.73m2). Marginal donors were defined by criteria including donation after cardiac death, age ≥65, severe macrosteatosis (≥30%), or body mass index≥40kg/m2. The primary outcome was to compare 3-year post-LT GS between patients with low and high pre-LT renal function. Additionally, we examined post-LT eGFR 1-3 months post-LT.RESULTS: Of 13279 LT recipients, 12851 had high pre-LT eGFR and 428 had low pre-LT eGFR. Kaplan-Meier survival analysis showed that recipients with low pre-LT eGFR had significantly lower 3-year GS compared to those with high eGFR (p<0.01). Recipients of organs from marginal donors also exhibited a significant reduction in 3-year GS (p<0.01). This adverse effect persisted within the same MELD3.0 category. Additionally, lower pre-LT eGFR was associated with an increased risk of post-LT kidney function deterioration, especially among those receiving grafts from marginal donors. Multivariable logistic regression identified recipient age>65 as a significant risk factor for post-LT kidney function decline (OR 3.34 [1.05-10.7]; p = 0.03).DISCUSSION: GS was notably worse in recipients with low pre-LT eGFR, particularly when matched with marginal donors. A recipient age>65 is a risk indicator for post-LT kidney function deterioration with marginal donors, underscoring the importance of careful donor-recipient matching, especially with compromised pre-LT kidney function.
View details for DOI 10.1111/ctr.70123
View details for PubMedID 40062522
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Effect of sarcopenia on the survival of patients undergoing liver transplantation: a meta-analysis.
Surgery today
2025
Abstract
PURPOSE: The relationship between sarcopenia and post-liver transplant (LT) mortality is still not well understood. This study aims to provide an updated and comprehensive meta-analysis evaluating the impact of sarcopenia on the survival of LT patients.METHODS: We conducted searches in PubMed, Web of Science, and EMBASE up until May 2, 2024, without language restrictions. The primary outcome measured was the overall post-LT mortality risk associated with sarcopenia. The DerSimonian-Laird random effects model was used to calculate pooled adjusted hazard ratios (HRs).RESULTS: Eighteen cohort studies comprising a total 6297 LT patients were included. The overall prevalence of sarcopenia was 27% (95% CI: 26%-28%), and this rate was lower when sarcopenia was defined using the third lumbar-skeletal muscle index in men, and among patients with lower Child-Pugh class. Sarcopenia remained significantly associated with higher mortality, with a pooled adjusted HR of 1.55 (95% CI 1.28-1.89). This association held across subgroups based on sex, study location, sarcopenia definition, study quality, and living donor LT recipients. A sensitivity analysis excluding groups with a high proportion of hepatocellular carcinoma patients showed similar findings (HR 1.63, 95% CI 1.13-2.35). No significant heterogeneity was identified in any of the analyses.CONCLUSIONS: This meta-analysis shows that sarcopenia is significantly associated with increased mortality after LT. Thus, the risk of sarcopenia should be factored into the initial evaluation of LT candidates.
View details for DOI 10.1007/s00595-025-03008-y
View details for PubMedID 39928119
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Cluster analysis of hepatocellular carcinoma prognosis using preoperative alpha-fetoprotein and des-gamma-carboxy prothrombin levels: a multi-institutional study.
Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract
2025; 29 (4): 101980
Abstract
Hepatocellular carcinoma (HCC) remains the leading cause of cancer-related mortality worldwide and is characterized by high recurrence rates after curative resection. The tumor markers des-gamma-carboxy prothrombin (DCP) and alpha-fetoprotein (AFP) are crucial for HCC diagnosis and prognosis. However, their roles in the modern era of HCC epidemiology require reevaluation.This multi-institutional retrospective study analyzed 1515 patients who underwent hepatectomy for primary HCC. Patients were classified into 4 clusters using k-means analysis based on preoperative DCP and AFP levels. Clinicopathologic characteristics, overall survival (OS), and recurrence rate (RR) were evaluated using Cox proportional hazards models and area under the receiver operating characteristic curve (AUROC) comparisons.Cluster 3 (concurrent elevations of DCP and AFP) had the poorest 5-year OS (52.8%) and the highest RR (79.3%), whereas cluster 4 (low levels of both markers) had the most favorable outcomes, with a 5-year OS rate of 71.5% and an RR of 55.7%. Cluster 1 (elevated DCP alone) was associated with larger tumors (median of 45 mm) and more frequent vascular invasion (43%) than cluster 2 (elevated AFP alone, median tumor size of 24 mm, and vascular invasion of 36%). DCP was a stronger predictor of 5-year OS in patients with preserved liver function (AUROC, 0.63), whereas AFP was more effective in stratifying RR in patients with impaired liver function (AUROC, 0.57). Non-B, non-C hepatitis (NBNC)-related HCC exhibited a distinct biomarker profile, with an elevated DCP level correlating with a higher 5-year RR (67%) than other etiologies.Our study introduces tumor marker clustering as a novel analytical approach, providing a nuanced understanding of AFP and DCP's combined utility in predicting prognosis and recurrence. Our findings highlight the independent and complementary roles of these biomarkers, particularly in NBNC-related HCC and in cases with impaired liver function. AFP and DCP remain crucial tools for recurrence risk assessment, guiding personalized management strategies, such as surveillance, neoadjuvant therapies, and tailored postoperative interventions.
View details for DOI 10.1016/j.gassur.2025.101980
View details for PubMedID 39884550
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The urgent need for standardization in liver transplantation for unresectable colorectal liver metastases in the United States
ELSEVIER SCIENCE INC. 2025
View details for Web of Science ID 001460906400112
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Long-term outcomes of pediatric hepatoblastoma patients who present with metastasis and receive liver transplantation
ELSEVIER SCIENCE INC. 2025
View details for Web of Science ID 001460906400016
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The impact of sex and body mass index in liver transplantation for acute-on-chronic liver failure.
Journal of hepato-biliary-pancreatic sciences
2024
Abstract
There have been no studies evaluating how body mass index (BMI) impacts on waitlist and post-liver transplant (LT) mortality in acute-on-chronic liver failure (ACLF) by sex. We aimed to determine these impacts using the United Network for Organ Sharing (UNOS) database.Adults listed for LT with estimated ACLF (Est-ACLF) (2005-2023) were identified and subdivided by sex and BMI (high/middle/low). Competing-risk analyses evaluated impacts on waitlist mortality. Kaplan-Meier analyses assessed post-LT survival. Multivariable Cox regression identified risk factors.Of 37 251 Est-ACLF patients, 14 534 (39.0%) were female. Females had higher 90-day waitlist mortality than males (subhazard ratio [sHR]: 1.20, p < .01). High/low BMI patients had higher mortality than middle (sHR: 1.08/1.11, p < .01). In females, high BMI was associated with higher mortality than low (sHR: 1.10, p = .02); in males, low BMI was associated with higher mortality than high/middle (sHR: 1.16/1.16 vs. high/middle, p < .01). Multivariable analyses showed in females, high BMI was a significant risk factor for waitlist mortality (sHR:1.21, p < .01), while low was not; in males, high/low BMI was significant, with low having higher sHR (1.17) than high (1.09). Post-LT survival showed no significant difference in females; in males, low BMI showed worse post-3-/5-year-LT survival (p < .01). Multivariable Cox regression showed for females, neither low nor high BMI was significant for post-LT survival; for males, low BMI was significant for 1-/3-/5-year-LT survival (HR: 1.30/1.30/1.22, p < .01).Our analysis of BMI's impact on LT outcomes in ACLF by sex enables risk stratification and provides a basis for adjusting BMI.
View details for DOI 10.1002/jhbp.12100
View details for PubMedID 39727045
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Hepatitis C-positive grafts for hepatitis C-negative recipients in liver transplantation: Buried treasure or depleting resource?
Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society
2024
Abstract
Long-term outcomes of using hepatitis C virus (HCV) positive donors in HCV-negative recipients in liver transplantation (LT) are not well established. Data from the United Network for Organ Sharing (UNOS) database between July 1, 2015, and December 31, 2023, were analyzed. The cohort included 44,447 HCV antibody-negative (Ab-) candidates who underwent deceased donor LT. Changes in case numbers and utilization rates of HCV-positive donors, divided into HCV-viremic (NAT+) or Ab+ nonviremic (Ab+/NAT-), were assessed. Kaplan-Meier analysis and propensity score matching were used to evaluate 5-year graft survival (GS). The number of HCV-viremic donation after brain death (DBD) donors and their use in LT for HCV Ab- recipients peaked at 640 donors in 2019 and 289 LTs in 2022. In contrast, Ab+ nonviremic DBD donations are rising, with 536 donors and 284 LTs in 2023. The utilization rate of viremic DBD grafts has continuously decreased despite increased willingness by waitlist candidates to accept them. HCV-positive donation after circulatory death (DCD) donors were seldom utilized in the study period. The 5-year GS rates for HCV-viremic, Ab+ nonviremic, and naïve donors were not significantly different in either DBD (p=0.56) or DCD (p=0.52). Furthermore, Ishak stage 2 or 3 fibrotic DBD grafts had similar 5-year GS to non-fibrotic grafts. The findings suggest that the long-term outcome of using HCV-viremic DBD or DCD grafts for HCV-negative recipients is comparable to that of other graft types, and that fibrotic grafts have the potential to expand the DBD donor pool.
View details for DOI 10.1097/LVT.0000000000000557
View details for PubMedID 39679922
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Revisiting the Prognostic Influences of Donor-Recipient Size Mismatch in Deceased Donor Liver Transplantation.
Transplantation direct
2024; 10 (11): e1722
Abstract
Background: Liver transplantation (LT) outcomes are influenced by donor-recipient size mismatch. This study re-evaluated the impact on graft size discrepancies on survival outcomes.Methods: Data from 53389 adult LT recipients from the United Network for Organ Sharing database (2013-2022) were reviewed. The study population was divided by the body surface area index (BSAi), defined as the ratio of donor body surface area (BSA) to recipient BSA, into small-for-size (BSAi<0.78), normal-for-size (BSAi 0.78-1.24), and large-for-size (BSAi>1.24) grafts in deceased donor LT (SFSD, NFSD, and LFSD). Multivariate Cox regression and Kaplan-Meier survival analyses were conducted.Results: The frequency of size mismatch in deceased donor LT increased over the past 10 y. SFSD had significantly worse 90-d graft survival (P<0.01), and LFSD had inferior 1-y graft survival among 90-d survivors (P=0.01). SFSD was hazardous within 90 d post-LT because of vascular complications. Beyond 1 y, graft size did not affect graft survival. LFSD risk within the first year was mitigated with lower model for end-stage liver disease (MELD) 3.0 scores (<35) or shorter cold ischemia time (<8h).Conclusions: The negative impacts on donor-recipient size mismatch on survival outcomes are confined to the first year post-LT. SFSD is associated with a slight decrease in 90-d survival rates. LFSD should be utilized more frequently by minimizing cold ischemia time to <8h, particularly in patients with MELD 3.0 scores below 35. These findings could improve donor-recipient matching and enhance LT outcomes.
View details for DOI 10.1097/TXD.0000000000001722
View details for PubMedID 39440201
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Does the introduction of acuity circle policy change split liver transplantation practice?
Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society
2024
Abstract
With the Acuity Circles (AC) policy aiming to reduce disparities in liver transplantation (LT) access, the allocation of high-quality grafts has shifted, potentially affecting the use and outcomes of split LT. Data from the United Network for Organ Sharing (UNOS) database (February 4, 2016, to February 3, 2024) were analyzed, including 1,470 candidates who underwent deceased donor split LT, with 681 adult and 789 pediatric cases. The study periods were divided into pre-AC (February 4, 2016, to February 3, 2020) and post-AC (February 4, 2020, to February 3, 2024). The study assessed changes in split LT volumes and examined the impact of center practices. Both adult and pediatric split LTs decreased in the initial three years post-policy change, followed by an increase in the final year, with an overall 11.9% and 13.9% decrease between the eras. Adult female split LT cases remained consistent, ensuring access for smaller recipients. High-quality "splittable" livers were increasingly allocated to high MELD patients (MELD-Na ≥30). Despite the overall decrease in case volume, adult split LT volume increased in newly active LDLT centers, with six centers increasing LDLT volume by over 50.0%. Pediatric split LT volumes decreased despite additional priorities for pediatric candidates. The number of split LTs decreased in the initial period after the AC policy introduction, but there was a consistent need for small female candidates. In the adult population, LDLT and split LT demonstrated a synergistic effect in boosting center transplant volumes, potentially improving access for female candidates who need small grafts.
View details for DOI 10.1097/LVT.0000000000000513
View details for PubMedID 39412327
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Evaluation of prognostic efficacy of liver immune status index in predicting postoperative outcomes in hepatocellular carcinoma patients: A multi-institutional retrospective study.
Journal of hepato-biliary-pancreatic sciences
2024
Abstract
Hepatocellular carcinoma (HCC) ranks third in cancer-related deaths globally. Despite treatment advances, high post-hepatectomy recurrence rates (RR), especially with liver fibrosis and hepatitis C virus infection, remain challenging. Key prognostic factors include vascular invasion and perioperative blood loss, impacting extrahepatic recurrence. Natural killer (NK) cells are crucial in countering circulating tumor cells through TRAIL-mediated pathways. The aim of this study was to validate the liver immune status index (LISI) as a predictive tool for liver NK cell antitumor efficiency, particularly in HCC patients with vascular invasion.A retrospective analysis of 1337 primary HCC hepatectomies was conducted by the Hiroshima Surgical Study Group of Clinical Oncology (HiSCO). Clinicodemographic data were extracted from electronic medical records. Prognostic indices (FIB-4, ALBI, ALICE, GNRI, APRI, and LISI) were evaluated using area under the receiver operating characteristic curve values. Survival analyses employed Kaplan-Meier estimations and log-rank tests.LISI significantly correlated with other prognostic markers and stratified patients into risk groups with distinct overall survival (OS) and RR. It showed superior predictive performance for 2-year OS and RR, especially in patients with vascular invasion. Over longer periods, APRI and FIB-4 index reliabilities improved. The HISCO-HCC score, combining LISI, tumor burden score, and alpha-fetoprotein levels, enhanced prognostic accuracy.LISI outperformed existing models, particularly in HCC with vascular invasion. The HISCO-HCC score offers improved prognostic precision, guiding immunotherapeutic strategies and individualized patient care in HCC.
View details for DOI 10.1002/jhbp.12070
View details for PubMedID 39313837
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Advanced viability assessment in machine perfusion: what lies ahead?
EBioMedicine
2024; 108: 105351
View details for DOI 10.1016/j.ebiom.2024.105351
View details for PubMedID 39278109
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Comment on "Age Matters: What Affects the Cumulative Lifespan of a Transplanted Liver?".
Annals of surgery open : perspectives of surgical history, education, and clinical approaches
2024; 5 (3): e475
View details for DOI 10.1097/AS9.0000000000000475
View details for PubMedID 39310331
View details for PubMedCentralID PMC11415112
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Effect of transjugular intrahepatic portosystemic shunt insertion on waitlist mortality and access to liver transplantation in budd-chiari syndrome.
Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society
2024
Abstract
BACKGROUND: The impact of transjugular intrahepatic portosystemic shunt (TIPS) on waitlist mortality and liver transplantation (LT) urgency in Budd-Chiari Syndrome (BCS) patients remains unclear.METHOD: We analyzed BCS patients listed for LT in the UNOS database(2002-2024) to assess TIPS's impact on waitlist mortality and LT access via competing-risk analysis. We compared trends across two phases:Phase1(2002-2011) and Phase2(2012-2024).RESULTS: Of 815 BCS patients, 263(32.3%) received TIPS at listing. TIPS group had lower MELD-Na scores(20vs22,p<0.01), milder ascites(p=0.01), and fewer Status1 patients(those at risk of imminent death while awaiting LT)(2.7%vs8.3%,p<0.01) at listing compared to those without TIPS. TIPS patients had lower LT rates(43.3%vs56.5%,p<0.01) and longer waitlist times(350vs113d,p<0.01). TIPS use increased in Phase2(64.3%vs35.7%,p<0.01). Of 426 transplanted patients, 134(31.5%) received TIPS, showing lower MELD-Na scores(24vs27,p<0.01) and better medical conditions(Intensive care unit:14.9%vs21.9%,p<0.01) at LT. Status1 patients were fewer (3.7%vs12.3%,p<0.01), with longer waiting days(97vs26d,p<0.01) in TIPS group. TIPS use at listing increased from Phase1(25.6%) to Phase2(37.7%). From Phase1 to Phase2, ascites severity improved, re-LT cases decreased(Phase1:9.8%vsPhase2:2.2%,p<0.01), and cold ischemic time slightly decreased(Phase1:7.0vsPhase2:6.4 hours,p=0.14). Median donor body mass index significantly increased. No significant differences were identified in patient/graft survival at 1-/5-/10-year intervals between phases or TIPS/non-TIPS patients. While 90-day waitlist mortality showed no significant difference(p=0.11), TIPS trended towards lower mortality(subHazard ratio[sHR]:0.70[0.45-1.08]). Multivariable analysis indicated that TIPS was a significant factor in decreasing mortality(sHR:0.45[0.27-0.77],p<0.01). TIPS group also showed significantly lower LT access(sHR:0.65[0.53-0.81],p<0.01). Multivariable analysis showed that TIPS was a significant factor in decreasing access to LT(sHR:0.60[0.46-0.77],p<0.01). Sub-group analysis excluding Status1 or HCC showed similar trends.CONCLUSION: TIPS in BCS patients listed for LT reduces waitlist mortality and LT access, supporting its bridging role.
View details for DOI 10.1097/LVT.0000000000000469
View details for PubMedID 39177578
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Interleukin-33 and liver natural killer cells: A novel perspective on antitumor activity in liver fibrosis.
Hepatology research : the official journal of the Japan Society of Hepatology
2024
Abstract
Liver fibrosis, heralding the potential progression to cirrhosis and hepatocellular carcinoma (HCC), compromises patient survival and augments post-hepatectomy recurrence. This study examined the detrimental effects of liver fibrosis on the antitumor functions of liver natural killer (NK) cells and the interleukin-33 (IL-33) signaling pathway.Our investigation, anchored in both human physiologies using living and deceased donor livers and the carbon tetrachloride (CCl4)-induced mouse fibrosis model, aimed to show a troubling interface between liver fibrosis and weakened hepatic immunity.The Fibrosis-4 (FIB-4) index emerged as a salient, non-invasive prognostic marker, and its elevation correlated with reduced survival and heightened recurrence after HCC surgery even after propensity matching (n = 385). We established a strong correlation between liver fibrosis and liver NK cell dysfunction by developing a method for extracting liver NK cells from the liver graft perfusate. Furthermore, liver fibrosis ostensibly disrupted chemokines and promoted IL-33 expression, impeding liver NK cell antitumor activities, as evidenced in mouse models. Intriguingly, our results implicated IL-33 in diminishing the antitumor responses of NK cells. This interrelation, consistent across both mouse and human studies, coincides with clinical data suggesting that liver fibrosis predisposes patients to an increased risk of HCC recurrence.Our study revealed a critical relationship between liver fibrosis and compromised tumor immunity, emphasizing the potential interference of IL-33 with NK cell function. These insights advocate for advanced immunostimulatory therapies targeting cytokines, such as IL-33, aiming to bolster the hepatic immune response against HCC in the context of liver fibrosis.
View details for DOI 10.1111/hepr.14102
View details for PubMedID 39134448
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Pancreaticoduodenectomy after bilirubin adsorption for distal cholangiocarcinoma with severe obstructive jaundice refractory to repeat preoperative endoscopic biliary drainage: a case report.
Clinical journal of gastroenterology
2024; 17 (4): 711-716
Abstract
The necessity of biliary drainage before pancreaticoduodenectomy remains controversial in cases involving malignant obstructive jaundice; however, the benefits of biliary drainage have been reported in cases with severe hyperbilirubinemia. Herein, we present the case of a 61-year-old man suffering from jaundice due to distal cholangiocarcinoma. In this case, obstructive jaundice was refractory to repeat endoscopic drainage and bilirubin adsorption. Hyperbilirubinemia persisted despite successful implementation of biliary endoscopic sphincterotomy and two rounds of plastic stent placements. Stent occlusion and migration were unlikely and oral cholagogues proved ineffective. Owing to the patient's surgical candidacy and his aversion to nasobiliary drainage due to discomfort, bilirubin adsorption was introduced as an alternative therapeutic intervention. Following repeated adsorption sessions, a gradual decline in serum total bilirubin levels was observed and pancreaticoduodenectomy was scheduled. The patient successfully underwent pancreaticoduodenectomy with portal vein resection and reconstruction and D2 lymph node dissection. After the surgery, the serum bilirubin levels gradually decreased and the patient remained alive, with no recurrence at 26 months postoperatively. Therefore, this case highlights the feasibility and safety of performing pancreaticoduodenectomy in patients with severe, refractory jaundice who have not responded to repeated endoscopic interventions and have partially responded to bilirubin adsorption.
View details for DOI 10.1007/s12328-024-01966-3
View details for PubMedID 38589719
View details for PubMedCentralID 6232618
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Evaluating Predictors of Quality in Liver NK Cells Among Deceased Donors.
Cell transplantation
2024; 33: 9636897241283289
Abstract
This study investigated the substantial variability in the quality of liver natural killer (NK) cells from deceased donors (DDs). This study assessed liver nonparenchymal cells from 51 DDs for activation receptors and cytotoxicity against K562 (leukemia) and HepG2 (hepatoma) cell lines. The results indicated variability in TNF-related apoptosis-inducing ligand (TRAIL) and NK stimulatory receptor NK group 2 member D (NKG2D) expression in liver NK cells from DDs, which correlated with cytotoxicity against tumor cell lines. In addition, the white blood cell (WBC) count, aspartate aminotransferase (AST) level, body mass index (BMI), and platelet count were significantly associated with enhanced TRAIL and NKG2D expression. A predictive score integrating AST/platelet ratio index, BMI, and WBC count was developed to effectively identify DDs with high antitumor activity in liver NK cells. This score is expected to predict DDs with high-quality liver NK cells, which can be used for the purpose of immunotherapies.
View details for DOI 10.1177/09636897241283289
View details for PubMedID 39907091
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Pheochromocytoma Crisis Rescued by Veno-Arterial Extracorporeal Membrane Oxygenation and Continuous Renal Replacement Therapy.
The American surgeon
2023; 89 (6): 2857-2860
Abstract
Pheochromocytoma is a rare catecholamine producing adrenal tumor. Pheochromocytoma crisis is a life-threatening condition inducing multiple organ failure and hemodynamic instability caused by too much catecholamines produced from pheochromocytoma. We report a 59-year-old woman with pheochromocytoma crisis rescued by veno-arterial extracorporeal membrane oxygenation (VA-ECMO), continuous renal replacement therapy (CRRT), and interval tumor resection. In June 2020, the patient was taken to our institution complaining of headache and left lower back pain. The patient developed cardiopulmonary arrest while at the emergency department. After extracorporeal cardiopulmonary resuscitation, the patient required VA-ECMO for hemodynamic support, and subsequently CRRT for catecholamine removal and acute kidney injury. After 1 month of hemodynamic management, the patient underwent left adrenalectomy. The postoperative course was uneventful and she was discharged on postoperative day 23. CRRT would be a safe and feasible option for catecholamine control in patients with acute kidney injury in pheochromocytoma crisis.
View details for DOI 10.1177/00031348211063573
View details for PubMedID 34962830
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Repeat hepatectomy for massive liver metastases from pheochromocytoma: a case report.
Clinical journal of gastroenterology
2023; 16 (3): 457-463
Abstract
In malignant pheochromocytoma, the survival benefit of metastasectomy remains unclear. However, excessive catecholamines secreted from pheochromocytomas can cause cardiovascular and cerebrovascular complications. Debulking metastasectomy can be performed to reduce excess catecholamine secretion when curative resection is impossible. We present a case of metastatic pheochromocytoma to the liver, wherein a significant reduction in catecholamine secretion was achieved by repeat debulking hepatectomy. A 62-year-old woman who had undergone left adrenalectomy for primary pheochromocytoma 10 years prior to our surgical management, had multiple liver metastases of pheochromocytoma. Curative hepatectomy was infeasible because of insufficient remnant liver volume; thus, debulking hepatectomy was conducted. Preoperatively, increased doses of alpha-blockers and catecholamine synthesis inhibitors were administered. Nevertheless, substantial fluctuations in blood pressure and massive hemorrhage were observed intraoperatively. Eight months after the initial hepatectomy, repeat hepatectomy for the remnant lesions was performed due to the worsening of catecholamine levels and catecholamine-related symptoms. The patient survived, with serum catecholamines remaining within the normal range after repeat hepatectomy. Repeat debulking hepatectomy for metastatic pheochromocytoma to the liver is a feasible treatment strategy to effectively decrease catecholamine secretion and alleviate the symptoms thereof. However, special attention should be paid to perioperative catecholamine management and intraoperative surgical techniques.
View details for DOI 10.1007/s12328-023-01784-z
View details for PubMedID 36943552
View details for PubMedCentralID 5587061
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Infectious Pulmonary Artery Pseudoaneurysm That Resolved with Conservative Treatment.
Internal medicine (Tokyo, Japan)
2022; 61 (20): 3089-3093
Abstract
Pulmonary artery pseudoaneurysms (PAPs) are rare but can cause massive hemoptysis if they rupture. Infectious PAPs are often treated by surgery or transcatheter embolization and are rarely treated conservatively with antibiotics. We herein report a case of PAP treated conservatively in a 21-year-old woman with lung abscess. Except for one massive hemoptysis early in the course, the patient responded well to the empirical therapy with ampicillin/sulbactam and systemic hemostatic agents. After six weeks of antibiotics, the pseudoaneurysm disappeared. Conservative therapy with careful observation can be considered in small infectious PAPs when there is a good clinical response to initial conservative therapy.
View details for DOI 10.2169/internalmedicine.9021-21
View details for PubMedID 35283388
View details for PubMedCentralID PMC9646333