The impact of normothermic machine perfusion and acuity circles on waitlist time, mortality, and cost in liver transplantation: A multicenter experience.

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. Adult patients listed for liver transplant (LT) at 2 academic centers from January 1, 2015, to September 1, 2023, were included (n=2773) to allow all patients ≥6 months follow-up from listing. Routine NMP was implemented on October 14, 2022. Waitlist outcomes were compared from pre-NMP pre-acuity circles (n=1460), pre-NMP with acuity circles (n=842), and with NMP (n=381). Median waitlist time was 79 days (IQR: 20-232 d) at baseline, 49 days (7-182) with acuity circles, and 14 days (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. The 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 Model for End-Stage Liver Disease at LT was lowest with NMP, but Model for End-Stage Liver Disease at listing was highest in this era ( p <0.0001). The median donor risk index 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 health care 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). The 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 health care costs.

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

OBJECTIVE: Assess cost and complication outcomes after liver transplantation (LT) using normothermic machine perfusion (NMP). BACKGROUND: 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 2 centers (January 1, 2019, to June 30, 2023) were included. Retransplants, splits, and combined grafts were excluded. End-ischemic NMP (OrganOx-Metra) was implemented in October 2022 for extended-criteria donation after brain death (DBDs), all donations after circulatory deaths (DCDs), and logistics. NMP cases were matched 1:2 with static cold storage controls (SCS) using the Balance-of-Risk [donation after brain death (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 values were comparable between groups. DCD-NMP grafts experienced reduced cumulative 90-day comprehensive complications index (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 pretransplant costs in the 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 health care costs-per-transplantation were comparable.

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.

Impact of autotransfusion on recurrence of colorectal cancer liver metastasis: Long-term follow-up of patients undergoing curative intent hepatectomy.

INTRODUCTION: Colorectal cancer liver metastasis (CRLM) occurs in upto 50% of cases and drives patient outcomes. Up-front liver resection is the treatment of choice in resectable cases. There is no consensus yet established as to the safety of intraoperative autotransfusion in liver resection for CRLM. METHODS: Patients undergoing curative-intent hepatectomy for CRLM at a single quaternary-care institution from 1999 to 2016 were included. Demographics, surgical variables, Fong Clinical Risk Score (FCRS), use of intraoperative auto and/or allotransfusion, and survival data were analyzed. Propensity score matching (PSM) was performed accounting for allotransfusion, extent of hepatectomy, FCRS, and systemic treatment regimens. RESULTS: Three-hundred sixteen patients were included. The median follow-up was 10.4 years (7.8-14.1 years). The median recurrence-free survival (RFS) and overall survival (OS) in all patients were 1.6 years (interquartile range: 0.63-6.6 years) and 4.4 years (2.1-8.7), respectively.  Before PSM, there was a significantly reduced RFS in the autotransfusion group (0.96 vs. 1.73 years, p = 0.20). There was no difference in OS (4.11 vs. 4.44 years, p = 0.118). Patients in groups of FCRS 0-2 and 3-5 both had reduced RFS when autotransfusion was used (p = 0.005). This reduction in RFS was further found when comparing autotransfusion versus no autotransfusion within the FCRS 0-2 group and within the FCRS 3-5 group (p = 0.027). On Cox-regression analysis, autotransfusion (hazard ratio = 1.423, 1.028-2.182, p = 0.015) remained predictive of RFS. After PSM, there were no differences in FCRS (p = 0.601), preoperative hemoglobin (p = 0.880), allotransfusion (p = 0.130), adjuvant chemotherapy (p = 1.000), immunotherapy (p = 0.172), tumor grade (p = 1.000), use of platinum-based chemotherapy (p = 0.548), or type of hepatic resection (p = 0.967). After matching, there was a higher rate of recurrence with autotransfusion (69.0% vs. 47.6%, p = 0.046). There was also a reduced time to recurrence in the autotransfusion group compared with the group without (p = 0.006). There was no difference in OS after PSM (p = 0.262). CONCLUSION: Autotransfusion may adversely affect recurrence in liver resection for CRLM. Until further studies clarify this risk profile, the use of intraoperative autotransfusion should be critically assessed on a case-by-case basis only when other resuscitation options are not available.

Immunotherapy Plus Locoregional Therapy Leading to Curative-Intent Hepatectomy in HCC: Proof of Concept Producing Durable Survival Benefits Detectable with Liquid Biopsy.

BACKGROUND: Immunotherapy has emerged as an improved systemic treatment for select patients with advanced unresectable HCC. Objective response is reported in 30% of patients, yet complete response (pCR) allowing for curative-intent resection is rare. Locoregional therapies (LRTs) seem to show synergistic effects with immunotherapy, though this effect has not been scientifically reported. We report a cohort of patients showing pCR to immunotherapy + LRT as a proof of concept for the proposed treatment approach for locally unresectable HCC. METHODS: Patients with unresectable HCC treated with immunotherapy as an intended destination therapy from 2016 to 2023 were included. The electronic health record was queried for oncologic information, locoregional therapies, surgical interventions, and long-term outcomes. Circulating tumor DNA (ctDNA) testing was obtained using Guardant360, and tumor mutational burden (TMB) was defined as the number of somatic mutations per megabase. RESULTS: Ninety-six patients with advanced HCC received immunotherapy + LRT as a destination therapy. In total, 11 of 96 patients showed a complete response according to mRECIST criteria. Four of these (36.4%) ultimately underwent curative-intent resection. The median follow-up was 24.9 (IQR 15.6-38.3) months. Overall survival rates in those with complete response at 1, 3, and 5 years were 100%, 91%, and 81.8%, respectively, which were significantly improved compared to those of the cohort not achieving pCR (p < 0.001). All four patients undergoing immunotherapy + LRT followed by curative-intent hepatectomy have no evidence of disease (NED). Of those undergoing surgery, ctDNA was cleared in 75% (n = 3), providing an additional objective measurement of complete response. All four patients were TMB+ before beginning this treatment course, with three being TMB-, indicating stable and complete disease response. CONCLUSIONS: Immunotherapy + locoregional therapy can help downstage a significant proportion of patients with initially unresectable HCC, allowing for curative-intent surgery. The survival benefit associated with complete response seems durable up to 3 years after achieving this response. ctDNA measurement was converted from positive to negative in this cohort, providing additional indication of response.

Comparing Outcomes of Minimally Invasive and Open Hepatectomy for Primary Liver Malignancies in Patients with Low-MELD Cirrhosis.

INTRODUCTION: Cirrhotic patients with primary liver cancer may undergo curative-intent resection when selected appropriately. Patients with T1 tumors and low-MELD are generally referred for resection. We aim to evaluate whether minimally invasive hepatectomy (MIH) is associated with improved outcomes versus open hepatectomy (OH). METHODS: NSQIP hepatectomy database 2014-2021 was used to select patients with T1 Hepatocellular Carcinoma (HCC) or Intra-hepatic Cholangiocarcionoma (IHCC) and low-MELD cirrhosis (MELD ≤ 10) who underwent partial hepatectomy. Propensity score matching was applied between OH and MIH patients, and 30-day postoperative outcomes were compared. Multivariable regression was used to identify predictors of post-hepatectomy liver failure (PHLF) in the selected population. RESULTS: There were 922 patients: 494 (53.6%) OH, 372 (40.3%) MIH, and 56 (6.1%) began MIH converted to OH (analyzed with the OH cohort). We matched 354 pairs of patients with an adequate balance between the groups. MIH was associated with lower rates of bile leak (HR 0.37 [0.19-0.72)], PHLF (HR 0.36 [0.15-0.86]), collections requiring drainage (HR 0.30 [0.15-0.63]), postoperative transfusion (HR 0.36 [0.21-0.61]), major (HR 0.45 [0.27-0.77]), and overall morbidity (HR 0.44 [0.31-0.63]), and a two-day shorter median hospitalization (3 vs. 5 days; HR 0.61 [0.45-0.82]). No difference was noted in operative time, wound, respiratory, and septic complications, or mortality. Regression analysis identified ascites, prior portal vein embolization (PVE), additional hepatectomies, Pringle's maneuver, and OH (vs. MIH) as independent predictors of PHLF. CONCLUSION: MIH for early-stage HCC/IHCC in low-MELD cirrhotic patients was associated with improved postoperative outcomes over OH. These findings suggest that MIH should be considered an acceptable approach in this population of patients.