Choon Hyuck David Kwon

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Background/Objectives: The use of extended-criteria donors (ECDs) is rapidly increasing, with higher risks for impaired outcomes after liver transplantation (LT). Normothermic machine perfusion (NMP) can enhance graft viability assessment, though lactate clearance as a viability marker lacks consensus in clinical practice. Methods: This study analyzed 213 adult liver transplants using NMP from October 2022 to January 2024. Perfusate lactate levels were measured with an Epoc^® reader and five lactate-based viability criteria were evaluated for predicting post-LT outcomes. Results: All livers cleared lactate at 6 h of NMP (median 0.51 mmol/L). However, 33 livers failed at least one lactate viability criterion. Thirteen livers (6.1%) were discarded based on traditional criteria, but discard rates would have been higher using Groningen (14.6%) or Brisbane (11.2%) criteria for lactate. Outcomes for the recipients of livers that failed the lactate criteria were comparable to those of recipients with livers meeting all criteria, including biliary complications (p = 0.63), graft survival (>0.99), and 6-month CCI (p = 0.89). ROC analysis revealed poor predictive value for graft survival for lactate clearance criteria (AUC 0.50), while lactate was outperformed by MEAF score (AUC 0.67). Conclusions: Lactate clearance alone does not predict outcomes, highlighting the need for further validation of alternative viability.

BackgroundCombined heart-liver transplantation from donation circulatory death (DCD) donors remains uncommon, and published experience with dual-organ normothermic machine perfusion (NMP) is limited.MethodsWe describe two sequential combined heart-liver transplants performed with dual-organ NMP. The first recipient had dilated restrictive cardiomyopathy with cirrhosis attributed to metabolic dysfunction-associated steatohepatitis. The second had complex congenital heart disease with a bidirectional Glenn physiology, chronic hypoxia, and congestive hepatopathy.ResultsSequential DCD CHLT procedures were completed without intraoperative reperfusion syndrome. NMP heart pump times were 187 and 300 minutes, liver pump times were 360 and 480 minutes, and total liver ischemic times were 614 and 632 minutes for patients 1 and 2, respectively. Patient 1 developed early hepatic allograft dysfunction and an anastomotic biliary stricture managed endoscopically, but bilirubin normalized to 0.2 mg/dL and left ventricular ejection fraction normalized to 65% to 70% at month 6. Patient 2 had transient right ventricular dysfunction and acute renal failure requiring dialysis. Both patients had normal serum bilirubin levels and left ventricular ejection fractions by 6 months post-transplantation. Patient 2 later died 7 months after transplant from complications of post-transplant lymphoproliferative disorder without evidence of primary cardiac or hepatic graft failure.ConclusionsSequential combined heart-liver transplantation from DCD donors using dual-organ NMP is feasible and can support good early graft function despite complex preservation logistics and recipient complexity, including adult congenital heart disease. Larger experience is needed to define optimal candidate selection and longer-term outcomes.

Background.: No study has assessed the effect of end-ischemic normothermic machine perfusion (NMP) on renal function in simultaneous liver-kidney (SLK) transplantation. We hypothesized that by mitigating liver ischemia/reperfusion injury, NMP exerts a renoprotective effect on kidney allografts. This study compares renal outcomes in SLK transplant recipients receiving NMP versus static cold storage (SCS) livers. Methods.: We analyzed deceased-donor SLK transplant recipients (January 2019–July 2024) with at least 6 mo follow-up (n = 85). Primary outcomes included delayed graft function (DGF) and functional-DGF (f-DGF; failure of serum creatinine to decrease 10% daily for 3 d in the first week). Liver Core Outcome Sets were reported. NMP recipients (n = 17) were propensity score–matched 1:2 to SCS controls (n = 34). Kidneys underwent hypothermic machine perfusion in both groups. Results.: Cohorts were well matched, although NMP had more donation after circulatory death donors ( P = 0.006). f-DGF was significantly lower in NMP versus SCS (35% versus 68%, P = 0.025); this persisted in the hepatorenal syndrome subcohort (27% versus 65%, P = 0.03). Post–reperfusion syndrome was lower in NMP ( P = 0.041). NMP demonstrated superior renal function: lower peak creatinine (2.58 versus 3.03 mg/dL, P = 0.031), higher lowest postoperative estimated glomerular filtration rate (25 versus 19 mL/min/1.73 m ² , P = 0.021), and reduced 6-mo dialysis requirement (6% versus 32%, P = 0.036). Conclusions.: In this cohort, NMP was associated with improved early renal recovery in SLK transplant recipients, characterized by lower rates of f-DGF and higher estimated glomerular filtration rate. These findings suggest that mitigating liver ischemia via NMP may provide secondary benefits to the simultaneous kidney allograft.

PURPOSE: Histotripsy is a noninvasive, nonionizing, nonthermal method of treating liver tumors receiving US Food and Drug Administration (FDA) clearance in October 2023. This study aims to describe histotripsy as a method of achieving local tumor control (LTC) for primary and secondary liver tumors. METHODS: All patients receiving histotripsy since FDA clearance (December 2023-December 2024) at four institutions (two academic; two private) with >30 days of active follow-up were included. Patients were classified into palliative intent and complete treatment intent. LTC was assessed using contrast-enhanced imaging on the basis of modified response evaluation criteria in solid tumors (mRECIST) and standardized ablation criteria at postoperative days (POD) 30 and 90. RESULTS: Forty-seven patients received intended complete treatment to 91 liver tumors. Three total complications were observed: two cases of skin irritation treated with topical ointment and one case of bacteremia. At 30 days, 95% (n = 86/91) of treated liver tumors were nonviable. Two patients (one each with hepatocellular carcinoma and hepatic adenoma) received repeat treatment between POD30 and POD90, both converted to complete response. Forty-four patients and 85 tumors achieved 90-day follow-up. Three patients demonstrated persistently viable disease at POD90, all who had demonstrated viable tumor at POD30. Thus, the calculated primary efficacy rate at POD90 was 94% (n = 80/85), and the secondary efficacy rate was 96% (n = 82/85). The two patients with viable disease had neuroendocrine (n = 1), breast, and colorectal metastases (n = 1). Control rates were similar between primary and secondary tumors on time-to-event analysis (log-rank P = .146). CONCLUSION: Histotripsy achieved high rates of LTC at 30 and 90 days in this preliminary multicenter cohort. Longer-term follow-up is needed to confirm stable results.

Similar to many other cancer types, liver malignancies pose the common challenges of late detection of primary tumors and recurrences. Liquid biopsies, which assess the presence of circulating tumor DNA, have emerged as a novel, non-invasive clinical tool for diagnostic and surveillance purposes. This review represents an introductory and comprehensive overview of the current circulating tumor DNA (ctDNA) literature relevant to primary and secondary liver malignancies. Herein, we highlight key findings, landmark discoveries, challenges, and future directions.

Background. Simultaneous cardiothoracic surgery and liver transplantation (LT) is a high-risk procedure associated with high mortality and morbidity rates. The use of normothermic machine perfusion (NMP) allows graft quality enhancement, assessment of liver viability, and logistics optimization, expanding the donor pool and reducing organ discard rate. We share our institution’s experience with simultaneous cardiothoracic surgery and LT, using NMP for liver graft preservation and viability assessment. Methods. Data was retrospectively collected from 14 patients who underwent simultaneous cardiothoracic surgery and LT with NMP for liver graft preservation from October 2022 to August 2023. Data was divided into 3 groups: combined heart transplant and LT, lungs transplant and LT, and nontransplant cardiothoracic surgery and LT. Results. All liver grafts were from brain-dead donors. Median machine perfusion times were 211 min (range, 186–242 min), 222 min (range, 211–246 min), and 627 min (range, 180–1003 min) across the 3 groups, respectively. Postreperfusion syndrome occurred in 3 patients (21%), with 5 (36%) readmitted within 30 d because of complications. Biliary complications developed in 5 patients (36%), and 2 (14%) experienced acute liver rejection within 90 d postsurgery. No mortality was recorded during the median 18-mo follow-up. Conclusions. NMP serves as a safe and valuable tool for patients in need of simultaneous cardiothoracic surgery and LT, potentially broadening the scope of eligibility for these complex procedures. Export

Background.: Augmentation of hepatic venous outflow is crucial in living donor liver transplantation (LDLT) to maximize functional graft size and prevent venous complications. We present details of our outflow augmentation technique for left lobe grafts (LLG) in adult LDLTs, which uses all recipient 3 hepatic veins and venoplasty of graft left and middle hepatic veins. This study examines the effectiveness of our technique in preventing outflow complications and the correlation between anatomical variations of the graft hepatic veins and surgical outcomes. Methods.: We retrospectively reviewed 88 patients who underwent LLG-LDLT between 2012 and 2023. The patients were classified into 3 groups based on the graft hepatic vein anatomy and usage of venoplasty: group 1 (n = 10, common trunk without venoplasty), group 2 (n = 62, common trunk with venoplasty), and group 3 (n = 16, no common trunk with venoplasty). Results.: No patient developed clinically significant venous outflow complications or graft loss related to venous outflow. There were no significant differences in complication rates or ascites production among the groups. Five-year graft survival was comparable among the groups (P = 0.43). Multiple regression analysis revealed that the model for end-stage liver disease score was the only independent risk factor for increased ascites after transplant (standardized beta, 0.546; t value,4.20; P < 0.001; 95% confidence interval, 0.287-0.804), but anatomical variations of the graft hepatic veins did not influence ascites output. Conclusions.: The recipient 3 hepatic vein outflow augmentation technique with graft venoplasty can be applied to various graft hepatic venous anatomy and effectively prevents outflow-related graft loss in LLG-LDLT.

Liver malignancies, both primary and metastatic tumors, are a major cause of cancer-related mortality. Colorectal cancer alone results in liver metastases in nearly 50% of patients, with approximately 85% presenting with unresectable disease. Similarly, hepatocellular carcinoma and intrahepatic cholangiocarcinoma frequently present at advanced stages, limiting curative options. Systemic therapies provide modest survival benefits, underscoring the need for alternative treatments. Locoregional approaches, such as thermal ablation and chemoembolization, while effective, have notable limitations, including invasiveness, peri-procedural risks, and the requirement to interrupt systemic treatments. Histotripsy is a novel, non-invasive method that uses focused ultrasound-induced cavitation to enable precise tumor ablation without heat or radiation. Our institution utilizes a multidisciplinary tumor board approach to evaluate patients for histotripsy, particularly in cases involving unresectable disease, complex surgical candidacy, palliative intent related to disease control and symptom management, or as bridging therapy for transplantation. Early results, including preclinical data and the THERESA and #HOPE4LIVER trials, highlight its efficacy in treating liver tumors with minimal complications. This review outlines institutional protocols for histotripsy, covering pre- and post-procedural management, along with ethical considerations of current treatment paradigms. As a patient-centered approach, histotripsy offers a novel treatment option with a favorable safety profile and compatibility with systemic therapies.