Safety and efficacy of simultaneous liver transplantation and sleeve gastrectomy in morbid obese end-stage liver disease patients: The LT-SG study.

INTRODUCTION: In obese patients, metabolic dysfunction-associated steatotic liver disease is becoming a leading aetiology of end-stage liver disease and hepatocellular carcinoma. Simultaneous liver transplantation and sleeve gastrectomy (LT-SG) has been proposed in the US, but the safety and efficacy of the procedure have not been widely explored in Europe. METHODS: Between January 2016 and December 2022, morbidly obese patients listed for LT at Tor Vergata University were enrolled in the LT-SG study. Primary outcomes were: i) safety expressed as 30- and 90-days overall survival (OS) and ii) major postoperative complications (Clavien-Dindo > IIIa). The secondary outcome was efficacy expressed as a 3-year %excess BMI loss(%EBMIL). RESULTS: Eleven patients were enrolled in the study. The median BMI at transplantation was 42 (IQR 38-48). Indications to LT-SG were HCC (63.6%) and cirrhosis (36.4%). In 54% of cases, donors had high-risk characteristics (ET-DRI>1.6). The 30 and 90-day OS were 63.6% and 54.5%, respectively. All deaths occurred in patients with p-SOFT>15 or in patients who had at least three of the following characteristics: >60 years, BMI >45, metabolic syndrome, MELD>25 or ET-DRI >1.6. The six months, 1, 2 and 3 years %excess BMI loss was 73%, 60%, 50% and 43%, respectively. CONCLUSIONS: LT-SG is a complex procedure thatmay carry excess risk in an unselected population. It should be considered only in highly selected patients. Standard donors are recommended and prioritization of severely obese patients on the waiting list should be considered.

The impact of center volume on the utilization and outcomes of machine perfusion technology in liver transplantation: An international survey.

INTRODUCTION: Machine perfusion (MP) was developed to expand the donor pool and improve liver transplantation (LT) outcomes. Despite optimal results in clinical trials, the real-world MP benefit in centers with low-/mid-volume activity (LVCs) is still being determined. METHODS: Online survey on MP for LT, distributed to worldwide LT-centers representatives. Variables of interest included logistics, technicalities, and outcomes. Responders were grouped into high-volume centers (HVCs) (>60 LTs/year) and LVCs and results compared. RESULTS: Sixty-seven centers were included, 36 HVCs and 31 LVCs. Significant differences in MP regarded: (I) existence of an established program (80.6% vs. 41.9%; p = 0.02), (II) presence of a dedicated perfusionist (58.3% vs. 22.6%; p = 0.006), (III) duration (>4 h: 47.2% vs. 16.1%; p = 0.01), (IV) routine use (20%-40% vs. 5%-20%; p = 0.002), (V) graft utilization (>50%: 75% vs. 51.6%; p = 0.009), (VI) 90-day patient-survival (90%-100% vs. 50%-90%; p = 0.001) and (VII) subjectively perceived benefit (always vs. only in selected ECD; p = 0.009). Concordance was found for indications, type, viability tests, graft-salvage, 90-day graft-loss, and major-complications. CONCLUSIONS: This study captured a picture of MP in real-world LT-practice. Significant disparities have surfaced between LVCs and HVCs regarding logistics, utilization, and results. To close this gap, efforts should be made to more efficiently deliver dedicated support, training and mentoring to LVC teams adopting MP technology.

Longterm Survival and Cost-Effectiveness of Immunosuppression Withdrawal After Liver Transplantation.

Lifelong immunosuppression (IS) after liver transplantation is associated with severe adverse effects and increased recipients' morbidity and mortality. Clinical operational tolerance has been reported in up to 40% in very well-selected recipients. Longterm survival and cost savings within the Italian national health system in operational tolerant recipients is reported. Seventy-five liver recipients were enrolled for IS withdrawal at our institution during the period from April 1998 to December 2015. The study population comprised 32 (42.7%) tolerant patients; 41 (54.7%) nontolerant patients needing uptake of IS after clinical or biopsy-proven rejection; and 2 (2.7%) immediate nontolerant patients who developed early rejection after the first drug reduction. The primary endpoint of the study was to assess the longterm patients and graft outcome; the secondary endpoint was the assessment of cost savings in the context of IS withdrawal. The follow-up was 95.0 months (interquartile range, 22.5-108.5 months). IS withdrawal did not result in patient nor graft loss and resulted in a major cost savings reaching about €630,000. In conclusion, longterm IS withdrawal represents a remarkable cost savings in the health care of liver recipients without exposing them to graft loss.

Impact of remnant vital tissue after locoregional treatment and liver transplant in hepatocellular cancer patients, a multicentre cohort study.

The role of pathological findings after locoregional treatments as predictors of hepatocellular cancer recurrence after liver transplantation has been poorly addressed. The aim of the study was to identify the role of remnant vital tissue (RVT) of the target lesion in predicting hepatocellular cancer recurrence. Two hundred and seventy-six patients firstly undergoing locoregional treatment and then transplanted between January 2010 and December 2015 in four European Transplant Centres (i.e. Rome Tor Vergata, Birmingham, Brussels and Ancona) were enrolled in the study to investigate the role of pathological response at upfront locoregional treatment. At multivariable Cox regression analysis, RVT ≥2 cm was a strong independent risk factor for post-LT recurrence (HR = 5.6; P < 0.0001). Five-year disease-free survival rates were 60.8%, 80.9% and 95.0% in patients presenting a RVT ≥2 cm vs. 0.1-1.9 vs. no RVT, respectively. When only Milan Criteria-IN patients were analysed, similar results were reported, with 5-year disease-free survival rates of 58.1%, 79.0% and 94.0% in patients presenting a RVT ≥2 cm vs. 0.1-1.9 vs. no RVT, respectively. RVT is an important determinant of tumour recurrence after liver transplantation performed for hepatocellular cancer. Its discriminative power looks to be evident also in a Milan-IN setting, suggesting to more liberally use locoregional treatments also in these patients.

Proposal and validation of a liver graft discard score for liver transplantation from deceased donors: a multicenter Italian study.

Several studies have explored the risk of graft dysfunction after liver transplantation (LT) in recent years. Conversely, risk factors for graft discard before or at procurement have poorly been investigated. The study aimed at identifying a score to predict the risk of liver-related graft discard before transplantation. Secondary aims were to test the score for prediction of biopsy-related negative features and post-LT early graft loss. A total of 4207 donors evaluated during the period January 2004-Decemeber 2018 were retrospectively analyzed. The group was split into a training set (n = 3,156; 75.0%) and a validation set (n = 1,051; 25.0%). The Donor Rejected Organ Pre-transplantation (DROP) Score was proposed: - 2.68 + (2.14 if Regional Share) + (0.03*age) + (0.04*weight)-(0.03*height) + (0.29 if diabetes) + (1.65 if anti-HCV-positive) + (0.27 if HBV core) - (0.69 if hypotension) + (0.09*creatinine) + (0.38*log10AST) + (0.34*log10ALT) + (0.06*total bilirubin). At validation, the DROP Score showed the best AUCs for the prediction of liver-related graft discard (0.82; p < 0.001) and macrovesicular steatosis ≥ 30% (0.71; p < 0.001). Patients exceeding the DROP 90th centile had the worse post-LT results (3-month graft loss: 82.8%; log-rank P = 0.024).The DROP score represents a valuable tool to predict the risk of liver function-related graft discard, steatosis, and early post-LT graft survival rates. Studies focused on the validation of this score in other geographical settings are required.

Feasibility and cost effectiveness of ambulatory laparoscopic cholecystectomy. A retrospective cohort study.

Ambulatory surgery is an efficient, safe and widely performed procedure; this study would shows the advantages of the ambulatory laparoscopic cholecystectomy procedure from the point of view of patients and the Hospital/National Health System. Materials and Methods: Single-center retrospective cohort study including 288 patients who underwent laparoscopic-cholecystectomy at **** from January 2016 to July 2018. Ambulatory LC were compared to well-matched inpatient procedures performed in the same study period. The primary endpoints was the 30-day readmission rate. Secondary endpoints were the discharge rate in the ambulatory group, the post-operative complications rate and cost effectiveness. Results: 120/288 (41.7%) patients underwent ambulatory laparoscopic cholecystectomy. Thirty-two (26.7%) patients who underwent ambulatory laparoscopic cholecystectomy had major preoperative comorbidities and 35 (29.2%) had undergone prior abdominal surgery. The readmission rates for ambulatory patients and inpatients were 0.8% and 1.7% (p = 0.56), respectively; 104 (86.7%) ambulatory patients were discharged successfully on the same day. The two groups showed the same post-operative complication rate (p = 0.40). Ambulatory procedures resulted in related cost savings of more than 300% for the hospital and a remarkable financial benefit for the National Italian Healthcare System, accounting for savings exceeding € 27 000 per year. Conclusions: Ambulatory laparoscopic cholecystectomy is safe and cost effective. Since a third of ambulatory patients showed comorbidity or previous abdominal surgery, we believe that this procedure may be performed safely in a tertiary HPB centre, even in complex patients.

Liver transplantation with a normothermic machine preserved fatty nonagenarian liver: A case report.

INTRODUCTION: The use of organs from expanded criteria donors for Liver Transplantation (LT) represents a major challenge. In the current era of Normothermic Machine Perfusion (NMP), donor age boundaries are often overcome and may contribute to reduce the gap between supply and demand of organs suitable for transplantation. We report on a unique case of nonagenarian liver successfully transplanted after NMP. PRESENTATION OF CASE: A fatty previously declined liver graft from nonagenarian male brain death donor underwent NMP (OrganOx Metra®, UK, Oxford) perfusion at University of Rome Tor Vergata on April 2018. The histology assessment showed 15% macro and 35% micro vescicular steatosis. Liver fulfilled viability criteria after NMP and was thus transplanted. The recipient was a 53 years old male with hepatocellular carcinoma who underwent two previous trans-arterial chemo-embolization. The post-LT AST peak was 1556 U/L; post operative course was characterized by hepatic artery thrombosis that required re-laparotomy and successful thrombectomy. Recipient experienced biliary stricture three months after discharge successfully treated by endoscopic retrograde cholangiopancreatography. At 7 months of follow-up patient has good clinical status and graft function. DISCUSSION: NMP represents a safe approach in order to increase the usage of very old fatty livers, that otherwise would be declined because of the high risk of primary non function and death. CONCLUSION: Nonagenarian liver recruitment after NMP seems to be feasible but a major attention is advisable on the manipulation and cannulation of hepatic artery in order to avoid intimal damage that can lead hepatic artery thrombosis.

The efficacy and safety of mammalian target of rapamycin inhibitors ab initio after liver transplantation without corticosteroids or induction therapy.

BACKGROUND: Mammalian target of rapamycin inhibitors have been used along with corticosteroids and/or induction therapy immediately after liver transplantation. Our aim was to assess the safety and tolerability of everolimus ab initio after liver transplantation without corticosteroids or induction, as well as efficacy in terms of liver function, rejection and graft loss. METHODS: A retrospective observational study of 50 adult patients (86% males, median age 54 years, range 25-68) who were liver transplanted between 2009 and 2013 and followed for 12 months. All recipients received everolimus plus low doses of calcineurin inhibitors (n=38) or mycophenolate (n=12) without corticosteroids and/or induction from the day of transplant. RESULTS: The overall patient and graft survival was 80%. Liver function was stable during one year follow-up. No rejections or graft loss were observed. Only five patients (10%) required therapy for onset dyslipidemia. CONCLUSION: Everolimus-based immunosuppression regimen without corticosteroids and/or induction immediately after liver transplantation seems to be safe and effective when administered with low doses of calcineurin-inhibitor or mycophenolate; although these findings require further investigation, these regimens could avoid adverse effects of standard immunosuppression regimens with higher doses.