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Background and study aim: The traditional endoscopic therapy of anastomotic strictures (AS) after orthotopic liver transplantation (OLT) is multiple ERCPs with insertion of an increasing number of plastic stents side-by-side. Fully covered self-expanding metal stents (cSEMS) could be a valuable option to decrease the number of procedures needed or non-responders to plastic stents. This study aims to retrospectively analyze the results of AS endoscopic treatment by cSEMS and to identify any factors associated to its success. Patients and Methods Ninety-one patients (mean age 55.9 ± 7.6 DS; 73 males) from 9 Italian transplantation centers, had a cSEMS positioned for post-OLT AS between 2007 and 2017. 49 (54%) patients were treated with cSEMS as a second-line treatment. Results All the procedures were successfully performed without with no immediate complications. After ERCP, adverse events occurred in 11% of cases (2 moderate pancreatitis, 8 cholangitis). In 49 patients (54%) cSEMSs migrated. After cSEMS removal, 46 patients (51%) needed further endoscopic (45 patients) or radiologic (1 patient) treatments to solve the AS. Lastly, 7 patients underwent surgery. Multivariable stepwise logistic regression showed that cSEMS migration was the only factor associated with further treatments (OR 2.6, 95% CI 1.0-6.6; p-value 0.03); cSEMS implantation before 12 months from OLT was associated with stent migration (OR 5.2, 95% CI 1.7-16.0; p-value 0.004). Conclusions cSEMS appears to be a safe tool to treat AS. cSEMS migration is the main limitation to its routinary implantation and needs to be prevented, probably with the use of new generation anti-migration stents.

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Background: With the increasing use of extended-criteria donor organs, the interest around T-tubes in liver transplantation (LT) was restored whilst concerns regarding T-tube-related complications persist. Aim: To describe insertion and removal protocols implemented at our institution to safely use pediatric rubber 5-French T-tubes and subsequent outcomes in a consecutive series of adult patients. Methods: Data of consecutive adult LT patients from brain-dead donors, treated from March 2017 to December 2019, were collected (i.e., biliary complications, adverse events, treatment after T-Tube removal). Patients with upfront hepatico-jejunostomy, endoscopically removed T-tubes, those who died or received retransplantation before T-tube removal were excluded. Results: Seventy-two patients were included in this study; T-tubes were removed 158 d (median; IQR 128-206 d) after LT. In four (5.6%) patients accidental T-tube removal occurred requiring monitoring only; in 68 (94.4%) patients Nelaton drain insertion was performed according to our protocol, resulting in 18 (25%) patients with a biliary output, subsequently removed after 2 d (median; IQR 1-4 d). Three (4%) patients required endoscopic retrograde cholangiopancreatography (ERCP) due to persistent Nelaton drain output. Three (4%) patients developed suspected biliary peritonitis, requiring ERCP with sphincterotomy and nasobiliary drain insertion (only one revealing contrast extravasation); no patient required percutaneous drainage or emergency surgery. Conclusion: The use of pediatric rubber 5-French T-tubes in LT proved safe in our series after insertion and removal procedure refinements.

Long-term survival after liver transplantation (LT) for hepatocellular cancer (HCC) continues to increase along with the modification of inclusion criteria. This study aimed at identifying risk factors for 5- and 10-year overall and HCC-specific death after LT. A total of 1,854 HCC transplant recipients from 10 European centers during the period 1987-2015 were analyzed. The population was divided in three eras, defined by landmark changes in HCC transplantability indications. Multivariable logistic regression analyses were used to evaluate the significance of independent risk factors for survival. Five- and 10-year overall survival (OS) rates were 68.1% and 54.4%, respectively. Two-hundred forty-two patients (13.1%) had HCC recurrence. Five- and 10-year recurrence rates were 16.2% and 20.3%. HCC-related deaths peaked at 2 years after LT (51.1% of all HCC-related deaths) and decreased to a high 30.8% in the interval of 6 to 10 years after LT. The risk factors for 10-year OS were macrovascular invasion (OR = 2.71; P = 0.001), poor grading (OR = 1.56; P = 0.001), HCV status (OR = 1.39; P = 0.001), diameter of the target lesion (OR = 1.09; P = 0.001), AFP slope (OR = 1.63; P = 0.006), and patient age (OR = 0.99; P = 0.01). The risk factor for 10-year HCC-related death were AFP slope (OR = 4.95; P < 0.0001), microvascular (OR = 2.13; P < 0.0001) and macrovascular invasion (OR = 2.32; P = 0.01), poor tumor grading (OR = 1.95; P = 0.001), total number of neo-adjuvant therapies (OR = 1.11; P = 0.001), diameter of the target lesion (OR = 1.11; P = 0.002), and patient age (OR = 0.97; P = 0.001). When analyzing survival rates in function of LT era, a progressive improvement of the results was observed, with patients transplanted during the period 2007-2015 showing 5- and 10-year death rates of 26.8% and 38.9% (vs. 1987-1996, P < 0.0001; vs. 1997-2006, P = 0.005). LT generates long-term overall and disease-free survival rates superior to all other oncologic treatments of HCC. T

BACKGROUND & AIMS: In Italy, since August 2014, LT candidates with MELD≥30 receive a national allocation priority. This multi-center cohort study aims to evaluate waiting time in the list, dropout rate, and graft survival before and after introducing the macroarea sharing policy.METHODS: 4,238 patients registered from 2010 to 2018 have been enrolled and categorized in an ERA-1 Group (n=2,013; before August 2014) and an ERA-2 Group (n=2,225; during and after August 2014). Cox proportional hazard model was used to estimate the HR of receiving LT or death between the two ERAs. The Fine-Gray model was used to estimate the HR for dropout from the waiting list and graft loss, considering death as a competing risk event. A Fine-Gray model was also used to estimate risk factors of graft loss.RESULTS: MELD≥30 patients had a lower median waiting time in the list for LT (4vs.12 days, p<0.001) and a higher probability to be transplanted (HR=2.27, 95%CI 1.78-2.90; p=0.001) in the ERA-2 when compared to ERA-1. The subgroup analysis on 3,515 LTs confirmed ERA-2 (odds ratio=0.56, 95%CI=0.46-0.68; p=0.001) as a protective factor for better graft survival rate. The protective variables for lower dropouts on the waiting list were: ERA-2, high volume centers, no competition centers, male recipients, and hepatocellular carcinoma. The protective variables for graft loss were high volume center and ERA-2, while MELD≥30 remained related to a higher risk of graft loss.CONCLUSIONS: The national MELD≥30 priority allocation was associated with improved patient outcomes, although MELD≥30 had a higher risk of graft loss. The transplant centers volume and competition among centers may have a role in the recipient prioritization and outcome.CLINICAL TRIAL NUMBER: NCT04530240 LAY SUMMARY: After introducing the Italian national MELD≥30 priority, more LT, fewer dropouts, and shorter waiting times were observed in patients with MELD≥30. However, a higher risk of g

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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.

Background: The role of surgical resection of liver metastases in patients with breast cancer liver metastasis (BCLM) remains controversial. A systematic review and meta-analysis of prognostic factors related to survival after BCLM resection was performed. Methods: An electronic search of relevant publications was performed. Pooled outcome measures were expressed as hazard ratios (HRs), including 95% confidence interval values (95% CIs), and calculated through a random-effects model. Heterogeneity was tested through the I2 index. Results: Thirty-five publications reported analyses on prognostic factors and survival. A total of 2782 patients who underwent liver resection for BCLM were included. Positive axillary lymph nodes at breast cancer diagnosis were an unfavorable survival factor (HR 1.74, 95% CI 1.25 to 2.41, I2 = 0%). Cumulative predictive factor HRs (multiple liver metastases, size of the metastases, short interval between primary tumor and onset of liver disease) related to the BCLM pattern were 1.32 (95% CI 1.17 to 1.48, I2 = 71%) and 1.51 (95% CI 1.15 to 1.98, I2 = 76%) for surgical and pathological features (resection margin and presence of extrahepatic disease), respectively. Conclusion: Resection of BCLM may provide a survival benefit for selected patients. For better long-term results, surgical selection should consider both primary tumor and BCLM features such as negative axillary lymph nodes at breast resection, a single hepatic lesion, a time longer than 24 months between breast and hepatic diagnosis, and a realizable R0 liver resection. However, the high heterogeneity among studies suggests the need for an RCT to validate the present findings.

Introduction: Liver transplantation (LT) is burdened by the risk of post-operative morbidity. Identifying patients at higher risk of developing complications can help allocate resources in the perioperative phase. Controlling Nutritional Status (CONUT) score, based on lymphocyte count, serum albumin, and cholesterol levels, has been applied to various surgical specialties, proving reliable in predicting complications and prognosis. Our study aims to investigate the role of the CONUT score in predicting the development of early complications (within 90 days) after LT. Methods: This is a retrospective analysis of 209 patients with a calculable CONUT score within 2 months before LT. The ability of the CONUT score to predict severe complications, defined as a Comprehensive Complication Index (CCI) ≥42.1, was examined. Inverse Probability Treatment Weighting was used to balance the study population against potential confounders. Results: Patients with a CCI ≥42.1 had higher CONUT score values (median: 7 vs. 5, P-value < 0.0001). The CONUT score showed a good diagnostic ability regarding post-LT morbidity, with an AUC = 0.72 (95.0%CI = 0.64–0.79; P-value < 0.0001). The CONUT score was the only independent risk factor identified for a complicated post-LT course, with an odds ratio = 1.39 (P-value < 0.0001). The 90-day survival rate was 98.8% and 87.5% for patients with a CONUT score <8 and ≥8, respectively. Conclusions: Pre-operative CONUT score is a helpful tool to identify patients at increased post-LT morbidity risk. Further refinements in the score composition, specific to the LT population, could be obtained with prospective studies.

OBJECTIVE: Liver transplantation (LT) is associated with a significant bleeding and the high transfusion requirements (HTR) negatively affect the outcome of LT patients. Our primary aim was to identify potential predictors of intraoperative transfusion requirements. Secondarily, we investigated, the effect of transfusion requirements on different clinical outcomes, including short-term morbidity and mortality. PATIENTS AND METHODS: Data collected in 219 adult LT from a deceased donor, grouped according to HTR (defined as the need of 5 or more red blood cell units), were compared. RESULTS: We found that previous portal vein thromboses (p=0.0156), hemoglobin (Hb) (p<0.0001), International Normalized Ratio (INR) (p=0.0010) at transplant and veno-venous bypass (p=0.0048) independently predicted HTR. HTR was always associated with poorer outcomes, including higher simplified acute physiology II score at Intensive Care Unit admission (p=0.0005), higher rates of pulmonary infections (p=0.0015) and early rejection (p=0.0176), longer requirement of mechanical ventilation, (p<0.0001), more frequent need for hemodialysis after transplantation (p=0.0036), overall survival (p=0.0010) and rate of day-90 survival (p=0.0016). CONCLUSIONS: This study identified specific risk factors for HTR and confirmed the negative impact exerted by HTR on clinical outcomes, including recipient survival. Prospective investigations are worth to assess whether correcting pre-transplant Hb and INR levels may effectively reduce blood product need and improve prognosis.