First-in-human liver transplantation from a centenarian deceased donor after brain death.

Liver transplantation from elderly donors is expanding due to demand for liver grafts, aging of recipients and donors, and introduction of machine perfusion. We report on a liver transplant from a 100-year-old deceased donor after brain death. The liver was transplanted after the use of hypothermic machine perfusion to a 60-year-old recipient with advanced hepatocellular carcinoma undergoing neoadjuvant immunotherapy. Nine months after the transplant, the patient is alive with a functioning graft and no evidence of acute rejection or tumor recurrence.

Robotic versus laparoscopic liver resections: propensity-matched comparison of two-center experience.

BACKGROUND: The advantages of the robotic approach in minimally invasive liver surgery (MILS) are still debated. This study compares the short-term outcomes between laparoscopic (LLR) and robotic (RLR) liver resections in propensity score matched cohorts. METHODS: Data regarding minimally invasive liver resections in two liver surgery units were retrospectively reviewed. A propensity score matched analysis (1:1 ratio) identified two groups of patients with similar characteristics. Intra- and post-operative outcomes were then compared. The difficulty of MILS was based on the IWATE criteria. RESULTS: Two hundred sixty-nine patients underwent MILS between January 2014 and December 2021 (LLR = 192; RLR = 77). Propensity score matching identified 148 cases (LLR = 74; RLR = 74) consisting of compensated cirrhotic patients (100%) underwent non-anatomic resection of IWATE 1-2 class (90.5%) for a solitary tumor < 5 cm in diameter (93.2%). In such patients, RLRs had shorter operative time (227 vs. 250 min, p = 0.002), shorter Pringle's cumulative time (12 vs. 28 min, p < 0.0001), and less blood loss (137 vs. 209 cc, p = 0.006) vs. LLRs. Conversion rate was nihil (both groups). In RLRs compared to LLRs, R0 rate (93 vs. 96%, p > 0.71) and major morbidity (4.1 vs. 5.4%, p > 0.999) were similar, without post-operative mortality. Hospital stay was shorter in the robotic group (6.2 vs. 6.6, p = 0.0001). CONCLUSION: This study supports the non-inferiority of RLR over LLR. In compensated cirrhotic patients underwent resection of low-to-intermediate difficulty for a solitary nodule < 5 cm, RLR was faster, with less blood loss despite the shorter hilar clamping, and required shorter hospitalization compared to LLR.

Implementing a robotic liver resection program does not always require prior laparoscopic experience.

BACKGROUND: Preliminary experience in laparoscopic liver surgery is usually suggested prior to implementation of a robotic liver resection program. METHODS: This was a retrospective cohort analysis of patients undergoing robotic (RLR) versus laparoscopic liver resection (LLR) for hepatocellular carcinoma at a center with concomitant initiation of robotic and laparoscopic programs RESULTS: A total of 92 consecutive patients operated on between May 2014 and February 2019 were included: 40 RLR versus 52 LLR. Median age (69 vs. 67; p = 0.74), male sex (62.5% vs. 59.6%; p = 0.96), incidence of chronic liver disease (97.5% vs.98.1%; p = 0.85), median model for end-stage liver disease (MELD) score (8 vs. 9; p = 0.92), and median largest nodule size (22 vs. 24 mm) were similar between RLR and LLR. In the LLR group, there was a numerically higher incidence of nodules located in segment 4 (20.0% vs. 16.6%; p = 0.79); a numerically higher use of Pringle's maneuver (32.7% vs. 20%; p = 0.23), and a shorter duration of surgery (median of 165.5 vs. 217.5 min; p = 0.04). Incidence of complications (25% vs.32.7%; p = 0.49), blood transfusions (2.5% vs.9.6%; p = 0.21), and median length of stay (6 vs. 5; p = 0.54) were similar between RLR and LLR. The overall (OS) and recurrence-free (RFS) survival rates at 1 and 5 years were 100 and 79 and 95 and 26% for RLR versus 96.2 and 76.9 and 84.6 and 26.9% for LLR (log-rank p = 0.65 for OS and 0.72 for RFS). CONCLUSIONS: Based on our results, concurrent implementation of a robotic and laparoscopic liver resection program appears feasible and safe, and is associated with similar oncologic long-term outcomes.

The Role of Salvage Transplantation in Patients Initially Treated With Open Versus Minimally Invasive Liver Surgery: An Intention-to-Treat Analysis.

Despite gaining wide consensus in the management of hepatocellular carcinoma (HCC), minimally invasive liver surgery (MILS) has been poorly investigated for its role in the setting of salvage liver transplantation (SLT). A multicenter retrospective analysis was carried out in 6 Italian centers on 211 patients with HCC who were initially resected with open (n = 167) versus MILS (n = 44) and eventually wait-listed for SLT. The secondary endpoint was identification of risk factors for posttransplant death and tumor recurrence. The enrolled patients included 211 HCC patients resected with open surgery (n = 167) versus MILS (n = 44) and wait-listed for SLT between January 2007 and December 2017. We analyzed the intention-to-treat survival of these patients. MILS was the most important protective factor for the composite risk of delisting, posttransplant patient death, and HCC recurrence (OR, 0.26; 95% confidence interval [CI], 0.11-0.63; P = 0.003). MILS was also the only independent protective factor for the risk of post-SLT patient death (OR, 0.29; 95% CI, 0.09-0.93; P = 0.04). After propensity score matching, MILS was the only independent protective factor against the risk of delisting, posttransplant death, and HCC recurrence (OR, 0.22; 95% CI, 0.07-0.75; P = 0.02). On the basis of the current analysis, MILS seems protective over open surgery for the risk of delisting, posttransplant patient death, and tumor recurrence. Larger prospective studies balancing liver function and tumor stage are strongly favored to better clarify the beneficial effect of MILS for HCC patients eventually referred to SLT.

Dual aortic and portal perfusion at procurement prevents ischaemic-type biliary lesions in liver transplantation when using octogenarian donors: a retrospective cohort study.

Several risk factors for ischaemic-type biliary lesions (ITBL) after liver transplantation (LT) have been identified, but the role of portal vein perfusion at graft procurement is still unclear. This was a prospective study on double aortic and portal perfusion (DP) of liver grafts stratified by donor's decade (<60 yo; 60-69 yo; 70-79 yo and ≥80 yo) versus similar historical cohorts of primary, adult grafts procured with single aortic perfusion (SP) only. The primary study aim was to assess the role of DP on the incidence of ITBL. There was no difference in the incidence of overall biliary complications according to procurement technique for recipients of grafts <80 years. A higher incidence of ITBL was observed for patients receiving grafts ≥80 years and perfused through the aorta only (1.9 vs. 13.4%; P = 0.008). When analysing octogenarian grafts, donor male gender (HR = 6.4; P = 0.001), haemodynamic instability (HR = 4.9; P = 0.008), and type-2 diabetes mellitus (DM2) (HR = 3.0; P = 0.03) were all independent risk factors for ITBL, while double perfusion at procurement (HR = 0.1; P = 0.04) and longer donor intensive care unit (ICU) stay (HR = 0.7; P = 0.04) were protective factors. Dual aortic and portal perfusion has the potential to reduce post-transplant ITBL incidence for recipients of octogenarian donor grafts. Larger series are needed to confirm this preliminary experience.

Transjugular intrahepatic portosystemic shunt for hepatitis C virus-related portal hypertension after liver transplantation.

This is a single center retrospective review of 19 consecutive liver transplant (LT) patients with hepatitis C virus (HCV)-related graft recurrent hepatitis who underwent transjugular intrahepatic portosystemic shunt (TIPS) at a median interval of 21 months (range: 5-50) from LT. Indications were refractory ascites in 11 patients (57.9%), hydrothorax in six (31.6%), and both in two (10.5%). TIPS was successful in 94.7% of cases (18/19) with only one procedure-related mortality (5.3%) owing to sepsis on day 35. At a median follow-up of 23 months (range: one month-nine yr), TIPS allowed for symptoms resolution in 16 patients (84.2%), with ascites resolving in all cases and hydrothorax persisting in 2. Post-TIPS patient survival at six months, one yr, and three yr was 84.2%, 73.7%, and 56.8%, respectively. We compared these results with a control group of 29 patients with HCV recurrence but without unresponsive ascites or hydrothorax. Patients in the control group had better survival than patients undergoing TIPS placement. However, survival of TIPS patients with a MELD score lower than or equal to 12 was similar to that of the control group. We conclude that TIPS may be used to treat complications secondary to HCV.

A single-staggered dose of calcineurin inhibitor may be associated with neurotoxicity and nephrotoxicity immediately after liver transplantation.

The aim of the present work was to assess the incidence of neuro-nephrotoxicity after a single-staggered dose of calcineurin inhibitors (CI) with different immunosuppressive approaches. From January to December 2006, all liver transplantation (LT) recipients at risk of renal or neurological complications treated with extracorporeal photopheresis (ECP) + mycophenolate mofetil + steroids and staggered introduction of CI (ECP group) were compared with a historical control group on standard CI-based immunosuppression. The ECP group included 24 patients with a mean model for end-stage liver disease (MELD) score of 19.9 +/- 11.1. The control group consisted of 18 patients with a mean MELD score of 12.5 +/- 5.2 (p = 0.012). In the ECP group CI were introduced at a mean of 9.2 +/- 6.2 d (4-31 d) after LT. Five patients in the ECP group presented acute neuro-nephrotoxicity after the first CI administration on post-transplant d 4, 5, 6, 6, and 14. Overall patient survival at one, six, and 12 months was 100%, 95.8%, and 95.8% in the ECP group vs. 94.4%, 77.7%, and 72.2% in the control group (p < 0.001). In conclusion, we showed that CI toxicity may occur after a single-staggered dose administration, ECP seems to be a valuable tool for managing CI-related morbidity regardless of the concomitant immunosuppressive regimen, being associated with a lower mortality rate in the early post-transplant course.

Severe liver trauma: the transplant surgeon's perspective. A case report.

Patients with severe liver trauma may be referred to liver transplantation (LT), even though no universal algorithm is currently agreed upon. LT is usually performed as a two-stage procedure after failure of primary surgery or in the event of surgery-related acute liver failure (ALF), but pre-transplant patient management, appropriate selection criteria and prompt referral to LT centers are paramount for a favorable graft outcome. This is a report on a patient who underwent LT as a two-stage procedure for sepsis-related ALF after extended right hepatectomy for a complex abdominal blunt trauma. Prompt referral to the Liver Transplant Unit of the Cisanello Hospital, Pisa, where the whole spectrum of surgical options and intensive care support are available was crucial to allow successful LT in a timely fashion. Therefore, the authors strongly advocate the whole algorithm for patients with severe liver traumas be put under control of an experienced LT team in order to improve surgical results.

Alpha glucocorticoid receptor expression in different experimental rat models of acute lung injury.

BACKGROUND AND OBJECTIVES: Acute respiratory distress syndrome (ARDS) is a frequent form of hypoxiemic respiratory failure caused by the acute development of diffuse lung inflammation. Dysregulated systemic inflammation with persistent elevation of circulating inflammatory cytokines is the pathogenetic mechanism for pulmonary and extrapulmonary organ dysfunction in patients with ARDS. Glucocorticoids (GCs) have a broad range of inhibitory inflammatory effects, including inhibition of cytokines transcription, cellular activation and growth factor production. They inhibit the inflammatory pathways through two specific intracellular glucocorticoid receptors (GRs), named GR alpha and GR beta. The aim of our study was to evaluate the histologic evidence of inflammatory injury and the GR alpha uptake of resident and inflammatory cells in different experimental models of acute lung injury (ALI). METHODS: We studied four groups of rats: three different experimental rat models of lung injury and a control group. The ALI was caused by barotrauma (due to an overventilation), oleic acid injection and mechanical ventilation. Results were compared to nonventilated rat control group. The duration of mechanical ventilation was of 2.5h. At the end of each experiment, rats were sacrificed. Lung biopsies were evaluated for morphologic changes. The immunohistochemistry was performed to study GR alpha expression. RESULTS: Histologic evidence of lung injury (alveolar and interstitial edema, vascular congestion, alveolar haemorrhage, emphysema, number of interstitial cells and neutrophils, and destruction of alveolar attachments) were present in all ventilated groups. Barotrauma lead to an additional inflammatory response. GR alpha expression significantly increased in the three ventilated groups compared with nonventilated groups. GR alpha expression was highest in barotrauma group. CONCLUSIONS: These data indicate that ALI is associated with diffuse alveolar damage, up-regulation of the inflammatory response and GR alpha overexpression. Barotrauma is the most effective mechanism inducing acute lung inflammation and GR alpha overexpression.