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.

Educational Interventions on Pregnancy Vaccinations during Childbirth Classes Improves Vaccine Coverages among Pregnant Women in Palermo's Province.

Maternal immunization is considered the best intervention in order to prevent influenza infection of pregnant women and influenza and pertussis infection of newborns. Despite the existing recommendations, vaccination coverage rates in Italy remain very low. Starting from August 2018, maternal immunization against influenza and diphtheria-tetanus-pertussis were strongly recommended by the Italian Ministry of Health. We conducted a cross sectional study to estimate the effectiveness of an educational intervention, conducted during childbirth classes in three general hospitals in the Palermo metropolitan area, Italy, on vaccination adherence during pregnancy. To this end, a questionnaire on knowledge, attitudes, and immunization practices was structured and self-administered to a sample of pregnant women attending childbirth classes. Then, an educational intervention on maternal immunization, followed by a counseling, was conducted by a Public Health medical doctor. After 30 days following the interventions, the adherence to the recommended vaccinations (influenza and pertussis) was evaluated. At the end of the study 326 women were enrolled and 201 responded to the follow-up survey. After the intervention, among the responding pregnant women 47.8% received influenza vaccination (+44.8%), 57.7% diphtheria-tetanus-pertussis vaccination (+50.7%) and 64.2% both the recommended vaccinations (+54.8%). A significant association was found between pregnant women that received at least one vaccination during pregnancy and higher educational level (graduation degree/master's degree), employment status (employed part/full-time) and influenza vaccination adherence during past seasons (at least one during last five years). The implementation of vaccination educational interventions, including counseling by healthcare professionals (HCPs), on maternal immunization during childbirth courses improved considerably the vaccination adherence during pregnancy.

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.

The role of immunomodulation in ABO-incompatible adult liver transplant recipients.

BACKGROUND: ABO-incompatible (ABO-i) liver transplantation (LT) is a high-risk procedure due to the potential for antibody-mediated rejection (AMR) and cell-mediated rejection. The aim of the current report is to illustrate the results of a retrospective comparison study on the use of immunomodulation with therapeutic plasma exchange (TPE) associated to high-dose immunoglobulins (IVIg) and extracorporeal photopheresis (ECP) in ABO-i adult LT patients. PATIENTS AND METHODS: Between January 1996 and December 2005, 19 patients underwent ABO-i LT. The study was designed for a comparison between two groups of ABO-i LT. Group 1 (control group) consisted of 11 patients treated with TPE only. Group 2 (study group) included eight patients treated with TPE and IVIg. Moreover, all Group 2 patients received acute rejection prophylaxis with ECP. RESULTS: The graft survival at 6, 12, and 18 months was 63.6, 54.4, and 45.5% for Group 1 vs. 87.5, 87.5, and 87.5% for Group 2 (P < or = 0.001). In Group 1 there were 3(27.3%) cases of AMR; 5 (45.4%) biopsy-proven acute rejections (BPAR); 1 (9.1%) chronic rejection and 3 (27.3%) ischemic-type biliary lesions (ITBL). In Group 2 there were no cases of AMR, BPAR, chronic rejection, or ITBL (P = 0.013). CONCLUSION: At median follow-up of 568 days, TPE in combination with IVIg and ECP appears to protect the graft from AMR in ABO-i liver transplantation. Continued patient enrollment will allow validation of these preliminary observations or the opportunity to devise newer AMR-avoidance policies.

Avoiding calcineurin inhibitors in the early post-operative course in high-risk liver transplant recipients: The role of extracorporeal photopheresis.

The aim of this work is to report on the results of a single-center, prospective study on the feasibility of calcineurin-inhibitor (CNI)-staggered immunosuppression by use of extracorporeal photopheresis (ECP) in liver transplant (LT) recipients at risk of renal and neurological complications. Patients were matched on a 1:1 basis with historical controls on standard CNI immunosuppression. ECP patients were treated with ECP plus antimetabolites and/or steroids, while CNIs were withheld until clinically indicated. Thirty-six patients were evaluated: 18 ECP patients and 18 controls. ECP was tolerated in 100% of cases. CNI were introduced at a median of 8 days (4-55) in 17 ECP patients, while one patient was on a fully CNI-sparing regimen 22 months after LT. Acute rejection occurred in 27.7% patients in ECP (5/18) versus 16.7% in controls (3/18) (P = ns) with a shorter time to rejection in ECP (36 +/- 31.3 days vs. 83.6 +/- 65.6 days; P = ns). All rejection episodes were amenable to medical treatment. Neurological and renal complications occurred in 22.2% (4/18) of patients in either group, but led to in-hospital mortality in 3 patients among controls versus 1 in ECP (P = ns). One-, 6-, and 12-month survival rates were 94.4, 88.1, and 88.1% in ECP versus 94.4, 77.7, and 72.2% among controls (P < 0.0001). ECP seems to allow for management of high-risk LT recipients in the early post-transplant course and reduction of CNI-related mortality. Continued data validation is favored to assess the impact of ECP on long-term graft and patient survival.

Treatment of antibody-mediated rejection with high-dose immunoglobulins in ABO-incompatible liver transplant recipient.

ABO-incompatible liver transplantation (LT) entails high risk of antibody-mediated rejection (AMR) and poor graft survival. Different treatment modalities have been reported, but none with use of a 2-week course of high-dose polyclonal i.v. immunoglobulins (IVIg) associated with plasmapheresis without the use of steroid pulses or monoclonal antibody. A 60-year-old male patient with blood-group O, Caucasian, underwent urgent LT for acute liver failure after hepatectomy for HCV-related hepatocellular carcinoma. He was grafted with a 66-year-old, blood-group A, HCV-positive liver graft. Pretransplant conditioning consisted of plasmapheresis and immunosuppression was triple with tacrolimus (TAC), steroids, and mycophenolate mofetil with anti-IL2-R monoclonal antibodies, plasmapheresis if hemagglutinin level >1:8, and extracorporeal photopheresis. After reduction of liver function tests to baseline, the patient presented a tenfold increase in alanine aminotransferases (ALT) levels 7 days post-transplantation. AMR was confirmed on histology. Treatment consisted of IVIg (1.5 g/Kg/daily for the first 7 days, and 1 g/Kg/daily from day 8 to 14) with a 14-day course of plasmapheresis. No side effect was observed and daily blood IgG levels ranged between 24.4 and 36.4 g/l. At the end of the scheduled course ALT returned to baseline. A control liver biopsy 55 days after LT showed no rejection and replacement of necrosis with fibrous strands. This case may support the role of high-dose IVIg for treatment and/or prophylaxis of severe AMR.

Fever, mental impairment, acute anemia, and renal failure in patient undergoing orthotopic liver transplantation: posttransplantation malaria.

A case of post-transplant malaria is described. The patient presented fever and severe anemia after orthotopic liver transplantation. Diagnosis was made only after the review of donor characteristics. Although a high parasitemia was found at the moment of diagnosis, the treatment with quinine and doxycycline was successful. Donor epidemiology should always be considered for a prompt diagnosis of rare tropical diseases in the graft recipients.