Tumor Mutational Burden from Circulating Tumor DNA Predicts Recurrence of Hepatocellular Carcinoma After Resection: An Emerging Biomarker for Surveillance: An Emerging Biomarker for Surveillance.

OBJECTIVE: Describe the utility of circulating tumor DNA in the post-operative surveillance of hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: Current biomarkers for HCC like Alpha-fetoprotein (AFP) are lacking. ctDNA has shown promise in colorectal and lung cancers, but its utility in HCC remains relatively unknown. METHODS: Patients with HCC undergoing curative-intent resection from 11/1/2020-7/1/2023 received ctDNA testing using the Guardant360 platform. TMB is calculated as the number of somatic mutations-per-megabase of genomic material identified. RESULTS: Forty seven patients had post-operative ctDNA testing. Mean follow-up was 27 months and maximum was 43.2 months. Twelve patients (26%) experienced recurrence. Most (n=41/47, 87.2%) had identifiable ctDNA post-operatively; 55.3%(n=26) were TMB-not detected versus 45.7% (n=21) TMB-detectable. Post-operative identifiable ctDNA was not associated with RFS (P=0.518). Detectable TMB was associated with reduced RFS (6.9 vs. 14.7months, P=0.049). There was a higher rate of recurrence in patients with TMB (n=9/21, 42.9%, vs. n=3/26, 11.5%, P=0.02). Area-Under the Curve (AUC) for TMB-prediction of recurrence was 0.752 versus 0.550 for AFP. ROC-analysis established a TMB cut-off of 4.8mut/mB for predicting post-operative recurrence (P=0.002) and RFS (P=0.025). AFP was not correlated with RFS using the lab-normal cut-off (<11 ng/mL, P=0.682) or the cut-off established by ROC-analysis (>4.6 ng/mL, P=0.494). TMB-high was associated with poorer RFS on cox-regression analysis (HR=5.386, 95%CI1.109-26.160, P=0.037) while micro-vascular invasion (P=0.853) and AFP (P=0.439) were not. CONCLUSIONS: Identifiable TMB on post-operative ctDNA predicts HCC recurrence, and outperformed AFP in this cohort. Perioperative ctDNA may be a useful surveillance tool following curative-intent hepatectomy. Larger-scale studies are needed to confirm this utility and investigate additional applications in HCC patients, including the potential for prophylactic treatment in patients with residual TMB after resection.

Impact of Back-to-Base Normothermic Machine Perfusion on Complications and Costs: A Multi-Center, Real-World Risk-Matched Analysis.

OBJECTIVE: Assess cost and complication outcomes after liver transplantation (LT) using normothermic machine perfusion (NMP). SUMMARY BACKGROUND DATA: End-ischemic NMP is often used to aid logistics, yet its' impact on outcomes after LT remains unclear, as does its' true impact on costs associated with transplantation. METHODS: Deceased donor liver recipients at two centers (1/1/2019-6/30/2023) were included. Retransplants, splits and combined grafts were excluded. End-ischemic NMP (OrganOx-Metra®) was implemented 10/2022 for extended-criteria DBDs, all DCDs and logistics. NMP-cases were matched 1:2 with cold storage controls (SCS) using the Balance-of-Risk (DBD-grafts) and UK-DCD Score (DCD-grafts). RESULTS: Overall, 803 transplantations were included, 174 (21.7%) receiving NMP. Matching was achieved between 118 NMP-DBDs with 236 SCS; and 37 NMP-DCD with 74 corresponding SCS. For both graft types, median inpatient comprehensive complications index (CCI) values were comparable between groups. DCD-NMP grafts experienced reduced cumulative 90-day CCI (27.6 vs. 41.9, P=0.028). NMP also reduced the need for early relaparotomy and renal-replacement-therapy, with subsequently less-frequent major complications (Clavien-Dindo >IVa). This effect was more pronounced in DCD-transplants. NMP had no protective effect on early biliary complications. Organ acquisition/preservation costs were higher with NMP, yet NMP-treated grafts had lower 90-day pre-transplant costs in context of shorter waiting-list times. Overall costs were comparable for both cohorts. CONCLUSIONS: This is the first risk-adjusted outcome and cost analysis comparing NMP and SCS. In addition to logistical benefits, NMP was associated with a reduction in relaparotomy and bleeding in DBD-grafts, and overall complications and post-LT renal-replacement for DCDs. While organ acquisition/preservation was more costly with NMP, overall 90-day-healthcare costs-per-transplantation were comparable.

The Impact of Normothermic Machine Perfusion and Acuity Circles on Waitlist Time, Mortality and Cost in Liver Transplantation: A Multi-Center Experience.

BACKGROUND: Ex-situ normothermic machine perfusion (NMP) helps increase the use of extended criteria donor livers. However, the impact of an NMP program on waitlist times and mortality has not been evaluated. METHODS: Adult patients listed for liver transplant (LT) at two academic centers 1/1/2015-9/1/2023 were included (n=2773) to allow all patients >6-months follow-up from listing. Routine NMP was implemented on 10/14/2022. Waitlist outcomes were compared from pre-NMP pre-acuity-circles (n=1,460), pre-NMP with acuity circles (n=842) and with NMP (n=381). RESULTS: Median waitlist time was 79days (IQR 20-232 d) at baseline, 49days (7-182) with acuity circles, and 14days (5-56) with NMP (p<0.001). The rate of transplant-per-100-person-years improved from 61-per-100-person-years to 99-per-100-person-years with acuity circles, and 194-per-100-person-years with NMP (p<0.001). Crude mortality without transplant decreased from 18.3% (n=268/1460), to 13.3% (n=112/843), to 6.3% (n=24/381) p<0.001) with NMP. Incidence of mortality without LT was 15-per-100-person-years before acuity circles, 19-per-100 with acuity circles, and 9-per-100-person-years after NMP (p<0.001). Median MELD at LT was lowest with NMP, but MELD at listing was highest in this era (p<0.0001). Median DRI of transplanted livers at baseline was 1.54 (1.27-1.82), 1.66 (1.42-2.16) with acuity circles, and 2.06 (1.63-2.46) with NMP (p<0.001). Six-month post-LT survival was not different between eras (p=0.322). The total cost of healthcare while waitlisted was lowest in the NMP era ($53,683 vs. $32,687 vs. $23,688, p<0.001); cost-per-day did not differ between eras (p=0.152). CONCLUSION: Implementation of a routine NMP program was associated with reduced waitlist time and mortality without compromising short-term survival after liver transplant despite increased use of riskier grafts. Routine NMP use enables better waitlist management with reduced healthcare costs.

Intensive locoregional therapy before Liver Transplantation for colorectal cancer liver metastasis: A novel pre-transplant protocol.

BACKGROUND: We describe a novel pre-liver-transplant (LT) approach in colorectal liver metastasis (CRLM) allowing for improved monitoring of tumor biology and reduction of disease burden before committing a patient to transplantation. METHODS: Patients undergoing LT for CRLM at Cleveland Clinic were included. The described protocol involves intensive locoregional therapy with systemic chemotherapy, aiming to reach minimal disease burden revealed by PET scan and CEA. Patients with no detectable disease or irreversible treatment-induced liver injury undergo transplant. RESULTS: Nine patients received liver transplant out of 27 who were evaluated (33.3%). Median follow-up was 700 days. Seven patients (77.8%) received a living donor LT. Five had no detectable disease and four had treatment-induced cirrhosis. Pre-transplant management included chemotherapy (n=9) +/- Bevacizumab (n=6) and/or Anti-EGFR (n=6). Median pre-LT cycles of chemotherapy=16 (Range 10-40). Liver-directed therapy included Yttrium-90 (n=5), ablation (n=4), resection (n=4), and HAI-pump (n=3). Three patients recurred after LT. Actuarial 1- and 2-year recurrence-free survival were 75% (n=6/8) and 60% (n=3/5). Recurrence occurred in the lungs (n=1), liver graft (n=1), and lungs+paraaortic nodes (n=1). Patients with pre-LT detectable disease had reduced RFS (p=0.04). All patients with recurrence had histologically-viable tumor in the liver explant. Patients treated in our protocol (n=16) demonstrated improved survival versus those who were not candidates (n=11) regardless of transplant status (p=0.01). CONCLUSION: A protocol defined by aggressive pre-transplant liver-directed treatment and transplant for patients with undetectable disease or treatment-induced liver injury may help prevent tumor recurrence.

Update to 'A Contemporary Systematic Review on Liver Transplantation for Unresectable Liver Metastasis of Colorectal Cancer'.

Colorectal cancer is the second most common cause of cancer-related death worldwide, and half of patients present with colorectal liver metastasis (CRLM). Liver transplant (LT) has emerged as a treatment modality for otherwise unresectable CRLM. Since the publication of the Lebeck-Lee systematic review in 2022, additional evidence has come to light supporting LT for CRLM in highly selected patients. This includes reports of >10-year follow-up with over 80% survival rates in low-risk patients. As these updated reports have significantly changed our collective knowledge, this article is intended to serve as an update to the 2022 systematic review to include the most up-to-date evidence on the subject.

The impact of colonic allograft inclusion on intestinal transplantation outcomes: Results from UNOS/OPTN database analysis.

BACKGROUND: Outcomes of intestinal transplantation with colon allograft (ICTx) remain controversial. We aimed to assess the outcomes of ICTx in comparison to intestinal transplantation without colon (ITx) using the UNOS/OPTN registry database. METHODS: We retrospectively reviewed 2612 patients who received primary intestinal transplants from 1998 to 2020. The rates of acute rejection (AR) within 6 months after transplant were compared between ICTx and ITx. Risk factors of 6-month AR were examined using logistic regression model by era. Furthermore, conditional graft survival was analyzed to determine long-term outcomes of ICTx. RESULTS: Of 2612 recipients, 506 (19.4%) received ICTx. Graft and patient survival in ICTx recipients were comparable to those in ITx recipients. White ICTx recipients had a higher incidence of AR within 6 months compared to ITx during the entire study period (p = .002), colonic inclusion did not increase the risk of 6-month AR in the past decade. ICTx recipients who experienced 6-month AR had worse graft and patient survival compared to those who did not (p <.001 and p = .004, respectively). Among patients who did not develop 6-month AR, Cox proportional hazard model analysis revealed that colonic inclusion was independently associated with improved conditional graft survival. CONCLUSIONS: In the recent transplant era, colonic inclusion is no longer associated with a heightened risk of 6-month AR and may provide better long-term survival compared to ITx when AR is absent. Risk adjustment for rejection and proper immunosuppressive therapy are crucial to maximize the benefits of colonic inclusion.

Left Lobe First With Purely Laparoscopic Approach: A Novel Strategy to Maximize Donor Safety in Adult Living Donor Liver Transplantation.

OBJECTIVE: Evaluate outcome of left-lobe graft (LLG) first combined with purely laparoscopic donor hemihepatectomy (PLDH) as a strategy to minimize donor risk. BACKGROUND: An LLG first approach and a PLDH are 2 methods used to reduce surgical stress for donors in adult living donor liver transplantation (LDLT). But the risk associated with application LLG first combined with PLDH is not known. METHODS: From 2012 to 2023, 186 adult LDLTs were performed with hemiliver grafts, procured by open surgery in 95 and PLDH in 91 cases. LLGs were considered first when graft-to-recipient weight ratio ≥0.6%. Following a 4-month adoption process, all donor hepatectomies, since December 2019, were performed laparoscopically. RESULTS: There was one intraoperative conversion to open (1%). Mean operative times were similar in laparoscopic and open cases (366 vs 371 minutes). PLDH provided shorter hospital stays, lower blood loss, and lower peak aspartate aminotransferase. Peak bilirubin was lower in LLG donors compared with right-lobe graft donors (1.4 vs 2.4 mg/dL, P < 0.01), and PLDH further improved the bilirubin levels in LLG donors (1.2 vs 1.6 mg/dL, P < 0.01). PLDH also afforded a low rate of early complications (Clavien-Dindo grade ≥ II, 8% vs 22%, P = 0.007) and late complications, including incisional hernia (0% vs 13.7%, P < 0.001), compared with open cases. LLG was more likely to have a single duct than a right-lobe graft (89% vs 60%, P < 0.01). Importantly, with the aggressive use of LLG in 47% of adult LDLT, favorable graft survival was achieved without any differences between the type of graft and surgical approach. CONCLUSIONS: The LLG first with PLDH approach minimizes surgical stress for donors in adult LDLT without compromising recipient outcomes. This strategy can lighten the burden for living donors, which could help expand the donor pool.

The High Incidence of Occult Carcinoma in Total Hepatectomy Specimens of Patients Treated for Unresectable Colorectal Liver Metastases With Liver Transplant.

OBJECTIVE: To describe the rate of occult carcinoma deposits in total hepatectomy specimens from patients treated with liver transplant (LT) for colorectal liver metastases (CRLM). BACKGROUND: Previous studies have shown that patients with CRLM treated with systemic therapy demonstrate a high rate of complete radiographic response or may have disappearing liver metastases. However, this does not necessarily translate into a complete pathologic response, and residual invasive cancer may be found in up to 80% of the disappearing tumors after resection. METHODS: Retrospective review of 14 patients who underwent LT for CRLM, at 2 centers. Radiographic and pathologic correlation of the number of tumors and their viability before and after LT was performed. RESULTS: The median (interquartile range) number of tumors at diagnosis was 11 (4-23). The median number of chemotherapy cycles was 24 (16-37). Hepatic artery infusion was used in 5 patients (35.7%); 6 (42.9%) underwent surgical resection, and 5 (35.7%) received locoregional therapy. The indication for LT was unresectability in 8 patients (57.1%) and liver failure secondary to oncologic treatment in the remaining 6 (42.9%). Before LT, 7 patients (50%) demonstrated fluorodeoxyglucose-avid tumors and 7 (50%) had a complete radiographic response. Histopathologically, 11 patients (78.6%) had a viable tumor. Nine (64.2%) of the 14 patients were found to have undiagnosed metastases on explant pathology, with at least 22 unaccounted viable tumors before LT. Furthermore, 4 (57.1%) of the 7 patients who demonstrated complete radiographic response harbored viable carcinoma on explant pathology. CONCLUSIONS: A complete radiographic response does not reliably predict a complete pathologic response. In patients with unresectable CRLM, total hepatectomy and LT represent a promising treatment options to prevent indolent disease progression from disappearing CRLM.

Combined Liver Transplant and Cardiac Surgery: Long-Term Outcomes and Predictors of Success.

OBJECTIVE: We aim to report our institutional outcomes of single-staged combined liver transplantation (LT) and cardiac surgery (CS). SUMMARY BACKGROUND DATA: Concurrent LT and CS is a potential treatment for combined cardiac dysfunction and end-stage liver disease, yet only 54 cases have been previously reported in the literature. Thus, the outcomes of this approach are relatively unknown, and this approach has been previously regarded as extremely risky. METHODS: Thirty-one patients at our institution underwent combined cardiac surgery and liver transplant. Patients with at least one-year follow-up were included. The Leave-One-Out Cross-Validation (LOOCV) machine-learning approach was used to generate a model for mortality. RESULTS: Median follow-up was 8.2 years (IQR 4.6-13.6 y). One- and five-year survival was 74.2% (N=23) and 55% (N=17), respectively. Negative predictive factors of survival included recipient age>60 years (P=0.036), NASH-cirrhosis (P=0.031), Coronary Artery Bypass-Graft (CABG)-based CS (P=0.046) and pre-operative renal dysfunction (P=0.024). The final model demonstrated that renal dysfunction had a relative weighted impact of 3.2 versus CABG (1.7), age ≥60y (1.7) or NASH (1.3). Elevated LT+CS risk score was associated with an increased five-year mortality after surgery (AUC=0.731, P=<0.001). Conversely, the widely accepted STS-PROM calculator was unable to successfully stratify patients according to 1- (P>0.99) or 5-year (P=0.695) survival rates. CONCLUSIONS: This is the largest series describing combined LT+CS, with joint surgical management appearing feasible in highly selected patients. CABG and pre-operative renal dysfunction are important negative predictors of mortality. The four-variable LT+CS score may help predict patients at high risk for post-operative mortality.

Biliary complications following split liver transplantation in adult recipients: a matched pair analysis on single-center experience.

The utilization of split liver grafts can increase access to liver transplantation (LT) for adult patients, particularly when liver grafts are shared between 2 adult recipients. However, it is yet to be determined whether split liver transplantation (SLT) increases the risk of biliary complications (BCs) compared with whole liver transplantation (WLT) in adult recipients. This retrospective study enrolled 1441 adult patients who underwent deceased donor LT at a single-site between January 2004 and June 2018. Of those, 73 patients underwent SLTs. Graft type for SLT includes 27 right trisegment grafts, 16 left lobes, and 30 right lobes. A propensity score matching analysis selected 97 WLTs and 60 SLTs. Biliary leakage was more frequently seen in SLTs (13.3% vs. 0%; p <0.001), whereas the frequency of biliary anastomotic stricture was comparable between SLTs and WLTs (11.7% vs. 9.3%; p=0.63). Graft and patient survival rates of patients undergoing SLTs were comparable to those undergoing WLTs (p=0.42 and 0.57, respectively). In the analysis of the entire SLT cohort, BCs were seen in 15 patients (20.5%) including biliary leakage in 11 patients (15.1%) and biliary anastomotic stricture in 8 patients (11.0%) [both in 4 patients (5.5%)]. The survival rates of recipients who developed BCs were significantly inferior to those without BCs (p <0.01). By multivariate analysis, the split grafts without common bile duct increased the risk of BCs. In conclusion, SLT increases the risk of biliary leakage compared with WLT. Biliary leakage can still lead to fatal infection and thus should be managed appropriately in SLT.

The Current State of Liver Transplantation for Colorectal Liver Metastases in the United States: A Call for Standardized Reporting.

BACKGROUND: Current success in transplant oncology for select liver tumors, such as hepatocellular carcinoma, has ignited international interest in liver transplantation (LT) as a therapeutic option for nonresectable colorectal liver metastases (CRLM). In the United States, the CRLM LT experience is limited to reports from a handful of centers. This study was designed to summarize donor, recipient, and transplant center characteristics and posttransplant outcomes for the indication of CRLM. METHODS: Adult, primary LT patients listed between December 2017 and March 2022 were identified by using United Network Organ Sharing database. LT for CRLM was identified from variables: "DIAG_OSTXT"; "DGN_OSTXT_TCR"; "DGN2_OSTXT_TCR"; and "MALIG_TY_OSTXT." RESULTS: During this study period, 64 patients were listed, and 46 received LT for CRLM in 15 centers. Of 46 patients who underwent LT for CRLM, 26 patients (56.5%) received LTs using living donor LT (LDLT), and 20 patients received LT using deceased donor (DDLT) (43.5%). The median laboratory MELD-Na score at the time of listing was statistically similar between the LDLT and DDLT groups (8 vs. 9, P = 0.14). This persisted at the time of LT (8 vs. 12, P = 0.06). The 1-, 2-, and 3-year, disease-free, survival rates were 75.1, 53.7, and 53.7%. Overall survival rates were 89.0, 60.4, and 60.4%, respectively. CONCLUSIONS: This first comprehensive U.S. analysis of LT for CRLM suggests a burgeoning interest in high-volume U.S. transplant centers. Strategies to optimize patient selection are limited by the scarce oncologic history provided in UNOS data, warranting a separate registry to study LT in CRLM.

Growing experience of surgical gut rehabilitation: essential role in the management of gut failure in adult patients.

PURPOSE OF REVIEW: With the inherent therapeutic limitations of gut transplantation, the concept of surgical gut rehabilitation was introduced to restore nutritional autonomy in pediatric patients. With favorable outcomes in these young patients, there has been increasing interest in the applicability of gut rehabilitative surgery to a growing population of adults with gut failure due to various etiologies. We aim to review the current status of surgical gut rehabilitation for adult gut failure patients in the era of multidisciplinary gut rehabilitation and transplantation. RECENT FINDINGS: Indications for surgical gut rehabilitation have been gradually expanding, with gut failure after bariatric surgery recently added. Serial transverse enteroplasty (STEP) has been used with favorable outcomes in adult patients, including those with intrinsic intestinal disease. Autologous gut reconstruction (AGR) is the most frequently used surgical rehabilitative method; its outcome is further improved with conjunctive use of bowel lengthening and enterocyte growth factor as a part of comprehensive gut rehabilitation. SUMMARY: Accumulated experiences have validated the efficacy of gut rehabilitation for survival, nutritional autonomy, and quality of life in adults with gut failure of various etiology. Further progress is expected with growing experience around the world.

Blockade or deficiency of PD-L1 expression in intestinal allograft accelerates graft tissue injury in mice.

The importance of PD-1/PD-L1 interaction to alloimmune response is unknown in intestinal transplantation. We tested whether PD-L1 regulates allograft tissue injury in murine intestinal transplantation. PD-L1 expression was observed on the endothelium and immune cells in the intestinal allograft. Monoclonal antibody treatment against PD-L1 led to accelerated allograft tissue damage, characterized by severe cellular infiltrations, massive destruction of villi, and increased crypt apoptosis in the graft. Interestingly, PD-L1-/- allografts were more severely rejected than wild-type allografts, but the presence or absence of PD-L1 in recipients did not affect the degree of allograft injury. PD-L1-/- allografts showed increased infiltrating Ly6G+ and CD11b+ cells in lamina propria on day 4, whereas the degree of CD4+ or CD8+ T cell infiltration was comparable to wild-type allografts. Gene expression analysis revealed that PD-L1-/- allografts had increased mRNA expressions of Cxcr2, S100a8/9, Nox1, IL1rL1, IL1r2, and Nos2 in the lamina propria cells on day 4. Taken together, study results suggest that PD-L1 expression in the intestinal allograft, but not in the recipient, plays a critical role in mitigating allograft tissue damage in the early phase after transplantation. The PD-1/PD-L1 interaction may contribute to immune regulation of the intestinal allograft via the innate immune system.

Living Donor Liver Transplantation With Augmented Venous Outflow and Splenectomy: A Promised Land for Small Left Lobe Grafts.

OBJECTIVE: Living donor liver transplantation (LDLT) using small grafts, especially left lobe grafts (H1234-MHV) (LLG), continues to be a challenge due to small-for-size syndrome (SFSS). We herein demonstrate that with surgical modifications, outcomes with small grafts can be improved. METHODS: Between 2012 and 2020, we performed 130 adult LDLT using 61 (47%) LLG (H1234-MHV) in a single Enterprise. The median graft-to-recipient weight ratio was 0.84%, with graft-to-recipient weight ratio <0.7% accounting for 22%. Splenectomy was performed in 72 (56%) patients for inflow modulation before (n=50) or after (n=22) graft reperfusion. In LLG-LDLT, venous outflow was achieved using all three recipient hepatic veins. In right lobe graft (H5678) (RLG)-LDLT, the augmented graft right hepatic vein was anastomosed to the recipient's cava with a large cavotomy. Outcome measures include SFSS, early allograft dysfunction (EAD), and survival. RESULTS: Graft survival rates at 1, 3, and 5 years were 94%, 90%, and 83%, respectively, with no differences between LLG (H1234-MHV) and RLG (H5678). Splenectomy significantly reduced portal flow without increasing the complication rate. Despite the aggressive use of small grafts, SFSS and EAD developed in only 1 (0.8%) and 18 (13.8%) patients, respectively. Multivariable logistic regression revealed model for end-stage liver disease score and LLG (H1234-MHV) as independent risk factors for EAD and splenectomy as a protective factor (odds ratio: 0.09; P =0.03). For LLG (H1234-MHV)-LDLT, patients who underwent prereperfusion splenectomy tended to have better 1-year graft survival than those receiving postreperfusion splenectomy. CONCLUSIONS: LLG (H1234-MHV) are feasible in adult LDLT with excellent outcomes comparable to RLG (H5678). Venous outflow augmentation and splenectomy help lower the threshold of using small-for-size grafts without compromising graft survival.

The Prognostic Utility of Intraoperative Allograft Vascular Inflow Measurements in Donation After Circulatory Death Liver Transplantation.

Donation after circulatory death (DCD) liver transplantation improves deceased donor liver use and decreases waitlist burden, albeit at an increased risk of biliary complications and inferior graft survival. Employing liver vascular inflow measurements intraoperatively permits allograft prognostication. However, its use in DCD liver transplantation is hitherto largely unknown and further explored here. DCD liver transplantation patient records at a single center from 2005 to 2018 were retrospectively scrutinized. Intraoperative flow data and relevant donor parameters were analyzed against endpoints of biliary events and graft survival. A total of 138 cases were chosen. The incidence of cumulative biliary complications was 38%, the majority of which were anastomotic strictures and managed successfully by endoscopic means. The ischemic cholangiopathy rate was 6%. At median thresholds of a portal vein (PV) flow rate of <92 mL/minute/100 g and buffer capacity (BC) of >0.04, both variables were independently associated with risk of biliary events (P = 0.01 and 0.04, respectively). Graft survival was 90% at 12 months and 75% at 5 years. Cox regression analysis revealed a PV flow rate of <50 mL/minute/100 g as predictive of poorer graft survival (P = 0.01). Furthermore, 126 of these DCD livers were analyzed against a propensity-matched group of 378 contemporaneous donation after brain death liver allografts (1:3), revealing significantly higher rates (P < 0.001) of both early allograft dysfunction (70% versus 30%) and biliary complications (37% versus 20%) in the former group. Although flow data were comparable between both sets, PV flow and BC were predictive of biliary events only in the DCD cohort. Intraoperative inflow measurements therefore provide valuable prognostication on biliary/graft outcomes in DCD liver transplantation, can help inform graft surveillance, and its routine use is recommended.

Impact of the donor hepatectomy time on short-term outcomes in liver transplantation using donation after circulatory death: A review of the US national registry.

BACKGROUND: During the donor hepatectomy time (dHT), defined as the time from the start of cold perfusion to the end of the hepatectomy, liver grafts have a suboptimal temperature. The aim of this study was to analyze the impact of prolonged dHT on outcomes in donation after circulatory death (DCD) liver transplantation (LT). METHODS: Using the US national registry data between 2012 and 2020, DCD LT patients were separated into two groups based on their dHT: standard dHT (< 42 min) and prolonged dHT (≥42 min). RESULTS: There were 3810 DCD LTs during the study period. Median dHT was 32 min (interquartile range 25-41 min). Kaplan-Meier graft survival curves demonstrated inferior outcomes in the prolonged dHT group at 1-year after DCD LT compared to those in the standard dHT group (85.3% vs 89.9%; P < .01). Multivariate Cox proportional hazards models for 1-year graft survival identified that prolonged dHT [hazard ratio (HR) 1.46, 95% confidence interval (CI) 1.19 - 1.79], recipient age ≥ 64 years (HR 1.40, 95% CI 1.14 - 1.72), and MELD score ≥ 24 (HR 1.43, 95% CI 1.16 - 1.76) were significant predictors of 1-year graft loss. Spline analysis shows that the dHT effects on the risk for 1-year graft loss with an increase in the slope after median dHT of 32 min. CONCLUSION: Prolonged dHTs significantly reduced graft and patient survival after DCD LT. Because dHT is a modifiable factor, donor surgeons should take on cases with caution by setting the dHT target of < 32 min.

Overview of Physical, Neurocognitive, and Psychosocial Outcomes in Pediatric Intestinal Failure and Transplantation.

PURPOSE OF REVIEW: Intestinal failure and transplantation may significantly impact physical, neurocognitive, and psychosocial development in pediatric patients. Currently, there is a paucity of literature on the effects of intestinal failure and transplantation on these aspects of development. This article will review the current literature and discuss the short and long-term impacts as well as interventions to improve clinical outcomes in children with intestinal failure or those undergoing transplantation. RECENT FINDINGS: Psychological disorders, neurodevelopmental delay, and social maladaptation are frequently encountered in this patient population. While the main focus is often on medical management, equal emphasis should be placed on other aspects of development such as increasing social support and improving school performance. The transition to adulthood also presents many obstacles for patients and healthcare providers should anticipate challenges such as childbirth, employment, and raising a family. The pre-operative, perioperative, and post-operative periods all represent opportunities for medical intervention. Frequent monitoring of physical, psychosocial, and neurocognitive status helps to improve clinical outcomes and long-term quality of life. Future research should emphasize continued development of multidisciplinary programs and specialized services to help address the physical and psychosocial needs of children with intestinal failure as well as transplant recipients.

Two pumps or one pump? A comparison of human liver normothermic machine perfusion devices for transplantation.

BACKGROUND: Normothermic machine perfusion provides continuous perfusion to ex situ hepatic grafts through the portal vein and the hepatic artery. Because the portal vein has high flow with low pressure and the hepatic artery has low flow with high pressure, different types of perfusion machines have been employed to match the two vessels' infusion hemodynamics. METHODS: We compared transplanted human livers perfused through a 2-pump (n = 9) versus a 1-pump perfusion system (n = 6) where a C-clamp is used as a tubing constrictor to regulate hemodynamics. RESULTS: There was no significant difference between groups in portal vein or hepatic artery flow rate. The 1-pump group had more hemoglobin in the perfusate. However, there was no significant difference in plasma hemoglobin between the 2-pump and 1-pump groups at each time point or in the change in levels, proving no hemolysis occurred due to C-clamp tube constriction. After transplantation, the 2-pump group had two cases of early allograft dysfunction (EAD), whereas the 1-pump group had no EAD. There was no graft failure or patient death in either group during follow-up ranging from 20-52 months. CONCLUSIONS: Our data show that the 1-pump design provided the same hemodynamic output as the 2-pump design, with no additional hemolytic risk, but with the benefits of lower costs, easier transport and faster and simpler setting.

Five Hundred Patients With Gut Malrotation: Thirty Years of Experience With the Introduction of a New Surgical Procedure.

OBJECTIVES: Define clinical spectrum and long-term outcomes of gut malrotation. With new insights, an innovative procedure was introduced and predictive models were established. METHODS: Over 30-years, 500 patients were managed at 2 institutions. Of these, 274 (55%) were children at time of diagnosis. At referral, 204 (41%) patients suffered midgut-loss and the remaining 296 (59%) had intact gut with a wide range of digestive symptoms. With midgut-loss, 189 (93%) patients underwent surgery with gut transplantation in 174 (92%) including 16 of 31 (16%) who had autologous gut reconstruction. Ladd's procedure was documented in 192 (38%) patients with recurrent or de novo volvulus in 41 (21%). For 80 patients with disabling gastrointestinal symptoms, gut malrotation correction (GMC) surgery "Kareem's procedure" was offered with completion of the 270° embryonic counterclockwise-rotation, reversal of vascular-inversion, and fixation of mesenteric-attachments. Concomitant colonic dysmotility was observed in 25 (31%) patients. RESULTS: The cumulative risk of midgut-loss increased with volvulus, prematurity, gastroschisis, and intestinal atresia whereas reduced with Ladd's and increasing age. Transplant cumulative survival was 63% at 10-years and 54% at 20-years with best outcome among infants and liver-containing allografts. Autologous gut reconstruction achieved 78% and GMC had 100% 10-year survival. Ladd's was associated with 21% recurrent/de novo volvulus and worsening (P > 0.05) of the preoperative National Institute of Health patient-reported outcomes measurement information system gastrointestinal symptom scales. GMC significantly (P ≤ 0.001) improved all of the symptomatology domains with no technical complications or development of volvulus. GMC improved quality of life with restored nutritional autonomy (P < 0.0001) and daily activities (P < 0.0001). CONCLUSIONS: Gut malrotation is a clinicopathologic syndrome affecting all ages. The introduced herein definitive correction procedure is safe, effective, and easy to perform. Accordingly, the current standard of care practice should be redefined in this orphan population.

Long term outcomes and complications of reno-portal anastomosis in liver transplantation: results from a propensity score-based outcome analysis.

Diffuse splanchnic vein thrombosis (DSVT) remains a serious challenge in liver transplantation (LT). Reno-portal anastomosis (RPA) has previously been reported as a valid option for management of patients with DSVT during LT. The aim of this study was to evaluate post-transplant renal function and surgical outcomes of patients with DSVT who underwent RPA during LT. Between January 2005 and December 2017, 1270 patients underwent LT at our institution, including 16 with DSVT managed with RPA (RPA group). We compared renal function and surgical outcomes in these patients to outcomes in 48 propensity score (PS)-matched patients without thrombosis (control group), using a 1:3 matching model. The two groups had similar rates of postoperative portal vein thrombosis (PVT), renal dysfunction as measured by estimated glomerular filtration rate (eGFR), and overall postoperative complications (Clavien grade III), although the RPA group had a higher incidence of postoperative upper gastrointestinal (GI) bleeding (31.3% vs 4.2%; P = 0.009) that had no clinical consequence. There were no significant differences in five-year graft and patient survival rates between the groups (P = 0.133 and P = 0.166, respectively). RPA is an established technique in the management of patients with DSVT during LT, with comparable outcomes to patients without thrombosis. Our report is the first to demonstrate similar surgical outcomes, including long-term renal function, in LT recipients with or without RPA.