Abdominal normothermic regional perfusion in controlled donation after circulatory determination of death liver transplantation: Outcomes and risk factors for graft loss.

Postmortem normothermic regional perfusion (NRP) is a rising preservation strategy in controlled donation after circulatory determination of death (cDCD). Herein, we present results for cDCD liver transplants performed in Spain 2012-2019, with outcomes evaluated through December 31, 2020. Results were analyzed retrospectively and according to recovery technique (abdominal NRP [A-NRP] or standard rapid recovery [SRR]). During the study period, 545 cDCD liver transplants were performed with A-NRP and 258 with SRR. Median donor age was 59 years (interquartile range 49-67 years). Adjusted risk estimates were improved with A-NRP for overall biliary complications (OR 0.300, 95% CI 0.197-0.459, p < .001), ischemic type biliary lesions (OR 0.112, 95% CI 0.042-0.299, p < .001), graft loss (HR 0.371, 95% CI 0.267-0.516, p < .001), and patient death (HR 0.540, 95% CI 0.373-0.781, p = .001). Cold ischemia time (HR 1.004, 95% CI 1.001-1.007, p = .021) and re-transplantation indication (HR 9.552, 95% CI 3.519-25.930, p < .001) were significant independent predictors for graft loss among cDCD livers with A-NRP. While use of A-NRP helps overcome traditional limitations in cDCD liver transplantation, opportunity for improvement remains for cases with prolonged cold ischemia and/or technically complex recipients, indicating a potential role for complimentary ex situ perfusion preservation techniques.

Intraoperative Troponin Elevation in Liver Transplantation Is Independently Associated With Mortality: A Prospective Observational Study.

Intraoperative factors implicated in postoperative mortality after liver transplantation (LT) are poorly understood. Because LT is a particularly demanding procedure, we hypothesized that intraoperative myocardial injury may be frequent and independently associated with early postoperative outcomes. We aimed to determine the association between intraoperative high-sensitivity troponin (hsTn) elevation during LT and 30-day postoperative mortality. A total of 203 adult patients undergoing LT were prospectively included in the cohort and followed during 1 year. Advanced hemodynamic parameters and serial high-sensitivity troponin T (hsTnT) measurements were assessed at 6 intraoperative time points. The optimal hsTnT cutoff level for intraoperative troponin elevation (ITE) was identified. Patients were classified into 2 groups according to the presence of ITE. Independent impact of ITE on survival was assessed through survival curves and multivariate Cox regression analysis. Intraoperative cardiac function was compared between groups. Troponin levels increased early during surgery in the ITE group. Troponin values at abdominal closure were associated with 30-day mortality (area under the receiver operating caracteristic curve, [AUROC], 0.73; P = 0.005). Patients with ITE showing values of hsTnT ≥61 ng/L at abdominal closure presented higher 30-day mortality (29.6% versus 3.4%; P < 0.001). ITE was independently associated with 30-day mortality (hazard ratio, 3.8; 95% confidence interval, 1.1-13.8; P = 0.04) and with worse overall intraoperative cardiac function. The hsTnT upper reference limit showed no discriminant capacity during LT. Intraoperative myocardial injury identified by hsTn elevation is frequently observed during LT, and it is associated with myocardial dysfunction and short-term mortality. Determinations of hsTn may serve as a valuable intraoperative monitoring tool during LT.

Comprehensive Characterization of a Porcine Model of The "Small-for-Flow" Syndrome.

INTRODUCTION: The term "Small-for-Flow" reflects the pathogenetic relevance of hepatic hemodynamics for the "Small-For-Size" syndrome and posthepatectomy liver failure. We aimed to characterize a large-animal model for studying the "Small-for-Flow" syndrome. METHODS: We performed subtotal (90%) hepatectomies in 10 female MiniPigs using a simplified transection technique with a tourniquet. Blood tests, hepatic and systemic hemodynamics, and hepatic function and histology were assessed before (Bas), 15 min (t-15 min) and 24 h (t-24 h) after the operation. Some pigs underwent computed tomography (CT) scans for hepatic volumetry (n = 4) and intracranial pressure (ICP) monitoring (n = 3). Postoperative care was performed in an intensive care unit environment. RESULTS: All hepatectomies were successfully performed, and hepatic volumetry confirmed liver remnant volumes of 9.2% [6.2-11.2]. The hepatectomy resulted in characteristic hepatic hemodynamic alterations, including portal hyperperfusion, relative decrease of hepatic arterial blood flow, and increased portal pressure (PP) and portal-systemic pressure gradient. The model reproduced major diagnostic features including the development of cholestasis, coagulopathy, encephalopathy with increased ICP, ascites, and renal failure, hyperdynamic circulation, and hyperlactatemia. Two animals (20%) died before t-24 h. Histological liver damage was observed at t-15 min and at t-24 h. The degree of histological damage at t-24 h correlated with intraoperative PP (r = 0.689, p = 0.028), hepatic arterial blood flow (r = 0.655, p = 0.040), and hepatic arterial pulsatility index (r = 0.724, p = 0.066). All animals with intraoperative PP > 20 mmHg presented liver damage at t-24 h. CONCLUSION: The present 90% hepatectomy porcine experimental model is a feasible and reproducible model for investigating the "Small-for-Flow" syndrome.

Preconditioning by portal vein embolization modulates hepatic hemodynamics and improves liver function in pigs with extended hepatectomy.

BACKGROUND: Portal vein embolization is performed weeks before extended hepatic resections to increase the future liver remnant and prevent posthepatectomy liver failure. Portal vein embolization performed closer to the operation also could be protective, but worsening of portal hyper-perfusion is a major concern. We determined the hepatic hemodynamic effects of a portal vein embolization performed 24 hours prior to hepatic operation. METHODS: An extended (90%) hepatectomy was performed in swine undergoing (portal vein embolization) or not undergoing (control) a portal vein embolization 24 hours earlier (n = 10/group). Blood tests, hepatic and systemic hemodynamics, hepatic function (plasma disappearance rate of indocyanine green), liver histology, and volumetry (computed tomographic scanning) were assessed before and after the hepatectomy. Hepatocyte proliferating cell nuclear antigen expression and hepatic gene expression also were evaluated. RESULTS: Swine in the control and portal vein embolization groups maintained stable systemic hemodynamics and developed similar increases of portal blood flow (302 ± 72% vs 486 ± 92%, P = .13). Portal pressure drastically increased in Controls (from 9.4 ± 1.3 mm Hg to 20.9 ± 1.4 mm Hg, P < .001), while being markedly attenuated in the portal vein embolization group (from 11.4 ± 1.5 mm Hg to 16.1 ± 1.3 mm Hg, P = .061). The procedure also improved the preservation of the hepatic artery blood flow, liver function, and periportal edema. These effects occurred in the absence of hepatocyte proliferation or hepatic growth and were associated with the induction of the vasoprotective gene Klf2. CONCLUSION: Portal vein embolization preconditioning represents a potential hepato-protective strategy for extended hepatic resections. Further preclinical studies should assess its medium-term effects, including survival. Our study also supports the relevance of hepatic hemodynamics as the main pathogenetic factor of post-hepatectomy liver failure.

Early Measurement of Indocyanine Green Clearance Accurately Predicts Short-Term Outcomes After Liver Transplantation.

BACKGROUND: There are no accurate tools to predict short-term mortality or the need for early retransplantation after liver transplantation (LT). A noninvasive measurement of indocyanine green clearance, the plasma disappearance rate (PDR), has been associated with initial graft function. METHODS: We evaluated the ability of PDR to predict early mortality or retransplantation after LT. In this observational prospective study, 332 LT were analyzed. Donor, recipient, and intraoperative data were investigated. The ensuing score was prospectively evaluated in a validation cohort of 77 patients. RESULTS: Thirty-three patients reached the main endpoint. By multivariate analysis, the only independent predictors of the endpoint were PDR (odds ratio [OR], 0.85; 95% confidence interval, 0.79-0.92) and international normalized ratio (OR, 1.45; 95% confidence interval, 1.17-1.82). A risk score weighted by the OR was built using cutoff values of 2.2 or greater for international normalized ratio (1 point) and less than 10%/min for PDR (2 points). Four categories (0 to 3) were possible. The risk of early death or retransplantation was associated with the score (0, 4.4%; 1, 6.5%; 2, 12%; and 3, 50%; χ for trend, P < 0.001). The score was also associated with duration of mechanical ventilation and intensive care unit stay. The score had a good diagnostic performance in the validation cohort (sensitivity, 60%; specificity, 95.5%; positive predictive value, 66.7%; negative predictive value, 94.1%). CONCLUSIONS: A simple score obtained within the first day after LT predicts short-term survival and need for retransplantation and may prove useful when selecting diagnostic and therapeutic strategies.

Postchemoradiation laparoscopic resection and intraoperative electron-beam radiation boost in locally advanced rectal cancer: long-term outcomes.

BACKGROUND: In selected patients with rectal cancer, laparoscopic surgery is as safe as open surgery, with similar resection margins and completeness of resection. In addition, recovery is faster after laparoscopic surgery. We analyzed long-term outcomes in a group of patients with locally advanced rectal cancer (LARC) treated with preoperative therapy followed by laparoscopic surgery and intraoperative electron-beam radiotherapy (IOERT). METHODS AND MATERIALS: From June 2005 to December 2010, 125 LARC patients were treated with 2 induction courses of FOLFOX-4 (oxaliplatin 85 mg/m(2)/d1, intravenous leucovorin at 200 mg/m(2)/d1-2, and an intravenous bolus of 5-fluorouracil 400 mg/m(2)/d1-2) and preoperative chemoradiation (4,500-5,040 cGy) followed by total mesorectal excision (laparoscopic, 35 %; open surgery, 65 %) and a presacral boost with IOERT. RESULTS: Patients in the laparoscopic surgery group lost less blood (median 200 vs 350 mL, p < 0.01) and had a shorter hospital stay (7 vs 11 days; p = 0.02) than those in the open surgery group. Laparoscopic procedures were shorter than open surgery procedures (270 vs 302 min; p = 0.67). Postoperative morbidity (32 vs 44 %; p = 0.65), RTOG grade ≥3 acute toxicity (25 vs 25 %; p = 0.97), and RTOG grade ≥3 chronic toxicity (7 vs 9 %; p = 0.48) were similar in the laparoscopy and open surgery groups. The median follow-up time for the entire cohort of patients was 59.5 months (range 7.8-90); no significant differences were observed between the groups in locoregional control (HR 0.91, p = 0.89), disease-free survival (HR 0.80, p = 0.65), and overall survival (HR 0.67, p = 0.52). CONCLUSIONS: Postchemoradiation laparoscopically assisted IOERT is feasible, with an acceptable risk of postoperative complications, shorter hospital stay, and similar long-term outcomes when compared to the open surgery approach.