Background/Objectives: The shortage of liver grafts remains a major challenge in transplantation. Full-left-full-right (FLFR) split liver transplantation (SLT) expands the donor pool by providing two grafts for small adult recipients. However, prolonged cold ischemia time (CIT) and ischemia-reperfusion injury (IRI) limit its success. Methods: We report a case of FLFR SLT utilizing ex situ dual hypothermic oxygenated machine perfusion (DHOPE) to mitigate IRI and enhance graft viability. A brain-dead donor's liver was split under continuous DHOPE, followed by simultaneous transplantation into two adult recipients. Results: Both recipients exhibited stable graft function at one-year follow-up. DHOPE effectively reduced CIT and optimized postoperative recovery, with no major complications beyond Clavien-Dindo Grade IIIb. Conclusions: This is the first reported FLFR SLT using ex situ DHOPE for two adult recipients, demonstrating its feasibility in reducing CIT and improving outcomes. Machine perfusion may become a standard in FLFR SLT.

Collagen is the major protein of the extracellular matrix that provides mechanical strength to the tissues. The relationship between the development of complications and the quality and quantity of collagen fibres has not been investigated in the literature, yet. This was a prospective study of 392 patients who underwent subcostal laparotomy for confirmed or suspected gastrointestinal malignancy. Prior to abdominal closure a sample of transversalis fascia was collected. The area covered by collagen (ACC) was measured as the mean area covered by Picosirius stained fibres in three areas of the fascia. The primary endpoint of the study was the occurrence of complications, graded according to the Clavien-Dindo over a 90-day follow-up period. 392 patients were included in the study. A transversalis fascia sample was obtained in 354 patients (90.3

Background: Hypothermic oxygenated machine perfusion has emerged as a strategy to alleviate ischemic-reperfusion injury in liver grafts. Nevertheless, there is limited data on the effectiveness of hypothermic liver perfusion in evaluating organ quality. This study aimed to introduce a readily accessible real-time predictive biomarker measured in machine perfusate for post-transplant liver graft function. Methods: The study evaluated perfusate analytes over a 90-day postoperative period in 26 patients randomly assigned to receive a liver graft following dual hypothermic machine perfusion in a prospective randomized controlled trial. Machine perfusion was consistently conducted end-ischemically for at least 120 min, with real-time perfusate assessment at 30-min intervals. Graft functionality was assessed using established metrics, including Early Allograft Dysfunction (EAD). Results: Perfusate lactate concentration after 120 min of machine perfusion demonstrated significant predictive value for EAD (AUC ROC: 0.841, p = 0.009). Additionally, it correlated with post-transplant peak transaminase levels and extended hospital stays. Subgroup analysis revealed significantly higher lactate accumulation in livers with post-transplant EAD. Conclusions: Liver graft quality can be effectively assessed during hypothermic machine perfusion using simple perfusate lactate measurements. The reliability and accessibility of this evaluation support its potential integration into diverse transplant centers.

Background: Liver transplantation constitutes a well-established treatment for patients with end-stage liver disease and selected hepatic malignancies. The introduction of normothermic machine perfusion (NMP) offers a platform for both extracorporeal organ maintenance and viability assessment, especially for organs with suspicious malfunction. These organs, discarded by the majority of transplant centers (so-called ‘orphan livers’), may help to safely expand the donor pool thanks to pre-transplant appraisal; Methods: We identified all grafts undergoing normothermic ma-chine perfusions performed in the Department of General, Transplant, and Liver Surgery between December 2022 and August 2023. Their perfusion characteristics and immediate postoperative periods, as well as complications that occurred in the 90-day postoperative periods, were analyzed; Results: There were eight orphan liver grafts that underwent NMP in our Department. Postoperative complications occurring in patients receiving grafts after NMP did not seem associated with the procedure. One patient required laparotomy within the 90-day postoperative period due to biliary fistula and underwent bile duct stenting due to both fistula and nonanastomotic stricture. In one patient we observed the occurrence of anastomotic biliary stricture more than 90 days after LTx; Conclusions: NMP allows for the viability assessment of grafts with suspicious prepreservation malfunction. Some of these organs may help to expand the donor pool.

Liver transplantation is the only curative option for end-stage liver disease and is necessary for an increasing number of patients with advanced primary or secondary liver cancer. Many patient groups can benefit from this treatment, however the shortage of liver grafts remains an unsolved problem. Liver bioengineering offers a promising method for expanding the donor pool through the production of acellular scaffolds that can be seeded with recipient cells. Decellularization protocols involve the removal of cells using various chemical, physical, and enzymatic steps to create a collagenous network that provides support for introduced cells and future vascular and biliary beds. However, the removal of the cells causes varying degrees of matrix damage, that can affect cell seeding and future organ performance. The main objective of this review is to present the existing techniques of producing decellularized livers, with an emphasis on the assessment and definition of acellularity. Decellularization agents are discussed, and the standard process of acellular matrix production is evaluated. We also introduce the concept of the stepwise assessment of the matrix during decellularization through decellularization cycles. This method may lead to shorter detergent exposure times and less scaffold damage. The introduction of apoptosis induction in the field of organ engineering may provide a valuable alternative to existing long perfusion protocols, which lead to significant matrix damage. A thorough understanding of the decellularization process and the action of the various factors influencing the final composition of the scaffold is essential to produce a biocompatible matrix, which can be the basis for further studies regarding recellularization and retransplantation.

INTRODUCTION:Liver transplantation (LT) is a well-established method applied for the treatment of various liver diseases, including primary and secondary malignancies, as well as acute liver failure triggered by different mechanisms. In turn, liver failure (PHLF) is the most severe complication observed after liver resection (LR). PHLF is an extremely rare indication for LT. The aim of the present study was to assess the results of LT in patients with PHLF. METHODS:Relevant cases were extracted from the prospectively collected database of all LTs performed in our center. All clinical variables, details of the perioperative course of each patient and long-term follow-up data were thoroughly assessed. RESULTS:Between January 2000 and August 2023, 2703 LTs were carried out. Among them, six patients underwent LT for PHLF, which accounted for 0.2% of all patients. The median age of the patients was 38 years (range 24-66 years). All patients underwent major liver resection before listing for LT. The 90-day mortality after LT was 66.7% (4 out of 6 patients), and all patients experienced complications in the posttransplant course. One patient required early retransplantation due to primary non-function (PNF). The last two transplanted patients are alive at 7 years and 12 months after LT, respectively. CONCLUSIONS:In an unselected population of patients with PHLF, LT is a very morbid procedure associated with high mortality but should be considered the only life-saving option in this group.

Background:Data on routine hypothermic machine perfusion of livers procured from donors after brain death (DBD) are scarce, and the benefits of the method have only been demonstrated in extended criteria grafts. This study aimed to assess if end-ischemic dual hypothermic oxygenated machine perfusion (dHOPE) is superior to static cold storage (SCS) in preservation of livers procured from DBD donors with respect to long-term outcomes. Existing data on short-term outcomes favours dHOPE in patients receiving high-risk grafts.Methods:This prospective randomized controlled trial included 104 recipients of DBD livers randomly assigned to SCS arm (78 patients) and the dHOPE arm (26 patients). Endpoints of interest were the occurrence of biliary complications (biliary fistula, anastomotic, and nonanastomotic strictures) and overall patient and graft survival (GS) during the 2-year follow-up.Results:A total of 36 patients developed biliary complications (at least one event) - six events in dHOPE arm and 30 in SCS arm. There was no significant difference in biliary complications between groups (23.7 vs. 43.4%, P=0.11). No differences were found significant with respect to anastomotic (19.9 vs. 33.7%, P=0.20) and nonanastomotic strictures (0 vs. 11.1%, P=0.10) as well as biliary fistulas (11.7 vs. 12.2%, P=0.93). Survival analysis did not show significantly different results in the study population - overall survival: 92.3% in dHOPE and 83.9% in SCS (P=0.35), and GS: 92.3 and 81.4% (P=0.23), respectively. However, a significant difference in GS was noted in recipients of high-risk grafts - 100% in dHOPE and 73.1% in SCS, respectively (P=0.038).Conclusions:The long-term outcome data suggest that the routine use of dHOPE may be beneficial for recipients of high-risk grafts from DBD donors. The present study does not provide any evidence for the benefits of dHOPE in low-risk grafts.

OBJECTIVE:To assess whether end-ischemic hypothermic oxygenated machine perfusion (HOPE) is superior to static cold storage (SCS) in preserving livers procured from donors after brain death (DBD).BACKGROUND:There is increasing evidence of the benefits of HOPE in liver transplantation, but predominantly in the setting of high-risk donors.METHODS:In this randomized clinical trial, livers procured from DBDs were randomly assigned to either end-ischemic dual HOPE for at least 2 hours or SCS (1:3 allocation ratio). The Model for Early Allograft Function (MEAF) was the primary outcome measure. The secondary outcome measure was 90-day morbidity (ClinicalTrials. gov, NCT04812054).RESULTS:Of the 104 liver transplantations included in the study, 26 were assigned to HOPE and 78 to SCS. Mean MEAF was 4.94 and 5.49 in the HOPE and SCS groups ( P =0.24), respectively, with the corresponding rates of MEAF >8 of 3.8% (1/26) and 15.4% (12/78; P =0.18). Median Comprehensive Complication Index was 20.9 after transplantations with HOPE and 21.8 after transplantations with SCS ( P =0.19). Transaminase activity, bilirubin concentration, and international normalized ratio were similar in both groups. In the case of donor risk index >1.70, HOPE was associated with significantly lower mean MEAF (4.92 vs 6.31; P =0.037) and lower median Comprehensive Complication Index (4.35 vs 22.6; P =0.050). No significant differences between HOPE and SCS were observed for lower donor risk index values.CONCLUSION:Routine use of HOPE in DBD liver transplantations does not seem justified as the clinical benefits are limited to high-risk donors.

In liver transplantation, a side-to-side anastomosis is one of the commonly performed techniques of the inferior vena cava reconstruction. The authors report a case of an application of an endoscopic vascular linear stapler for a side-to-side caval anastomosis during deceased-donor liver transplantation. The back table procedure was performed in a standard fashion for a side-to-side anastomosis. The linear vascular stapler was introduced during the temporary clamping of the recipient's inferior vena cava and the anastomosis was created without problems. Suturing of the resulting defect completed the anastomosis. The use of the stapler resulted in a shortening of the anastomosis time. The staple line after the reperfusion of the graft was completely sealed. The patient's postoperative course was uncomplicated and post-operative ultrasound and computed tomography confirmed the patency of the anastomosis. This case demonstrates a novel approach to a side-to-side caval reconstruction during liver transplantation that enables a shortening of the implantation time and may improve the quality of anastomoses.

BACKGROUND Malignant and benign neuroendocrine tumors (NET) share many histopathological features. Liver transplantation (LT) is one of the liver-directed therapies for neuroendocrine liver metastases (NELM). The aim of this study was to determine the outcomes of patients undergoing LT for NELM. MATERIAL AND METHODS This was a retrospective study that included 19 patients who underwent LT for unresectable NELM between December 1989 and December 2022 in the Department of General, Transplant, and Liver Surgery of the Medical University of Warsaw. Kaplan-Meier estimator and Cox proportional hazards regression were used for statistical analyses. RESULTS The primary tumor was located most frequently in the pancreas. The median follow-up was 72.5 months. The overall survival (OS) was 94.7%, 88.0%, 88.0%, 70.4%, and 49.3% after 1, 3, 5, 10, and 15 years, respectively. Accordingly, the recurrence-free survival (RFS) rates were 93.8%, 72.9%, 64.8%, 27.8%, and 27.8% after 1, 3, 5, 10, and 15 years, respectively. Ki-67 index ≥5% was found as a risk factor for both worse OS (hazard ratio (HR) 7.13, 95% confidence intervals (95% CI) 1.32-38.63, P=0.023) and RFS (HR 13.68, 95% CI 1.54-121.52, P=0.019). Recipient age ≥55 years was a risk factor for worse RFS (P=0.046, HR 5.47, 95% CI 1.03-29.08). Multivariable analysis revealed Ki-67 ≥5% as the sole independent factor for worse OS (HR 13.78, 95% CI 1.48-128.56, P=0.021). CONCLUSIONS Patients with unresectable NELM achieve great OS and satisfying RFS after LT. The risk factors associated with worse outcomes are attributed to primary tumor aggressiveness.

BACKGROUND:Early liver retransplantation after liver transplantation (LT) is the ultimate salvage procedure for irreversible graft failure. The aim of this study was to assess the impact of early retransplantation on 90-day and 5-year patient survival. METHODS:This retrospective cohort study included 2185 patients after LT in the period between 1997 and 2019. First, the patients undergoing first retransplantation within 6 months after initial LT were compared with naïve LT patients for early mortality (within 90 days). Second, to assess late survival, the patients who had retransplantation and survived at least 90 days post LT were compared with naïve LT patients for 5-year overall survival. The patients undergoing late retransplantation (>6 months) were excluded from analyses. Fisher's exact test was used to compare groups for early survival and log-rank test for late survival. RESULTS:The cumulative 1-, 3-, and 5-year overall survival was 87.0%, 79.9%, 75.0%, respectively, and did not differ significantly between the groups. The patients undergoing early retransplantation had lower 90-day survival rate of 89.2% as compared to 95.7% for naïve LT patients (P < .001). CONCLUSIONS:The early liver retransplantation has profound impact on post-LT 90-day survival; however, patients who survive that period can achieve long overall survival comparable with naïve LT patients.

Background Laparoscopic liver resections offer potential benefits but may require advanced laparoscopic skills and are volume dependent. Methods This retrospective study included 12 patients who underwent major laparoscopic resection and 24 patients after open major liver resection for liver malignancy in the time period between September 2020 and May 2021. The primary outcomes were complications according to Clavien-Dindo classification and duration of hospital stay. Results Median duration of hospital stay in laparoscopic resection group (6 days) was significantly shorter than in open resection group (8 days) ( p = 0.046). Complications classified as grade II or higher were significantly less frequent in the laparoscopic resection group (2 patients) versus open resection group (13 patients) ( p = 0.031). Conclusions Although laparoscopic major liver resections should be limited to expert hepatobiliary centers and are characterized by long learning curve, this approach may offer favorable short-term outcomes even during launching a new program.

Background. This study aimed to examine the effect of transaminases' activities in the first posttransplant day on early (90-day) and late (5-year) graft survival. Methods. This retrospective cohort study included 612 patients after liver transplantation (LT) in the period between 2015 and 2019. Patients with acute liver failure and with vascular complications after LT were excluded. The natural logarithms of alanine transaminase (ALT) and aspartate transaminase (AST) were used for analyses using the logistic regression and Cox proportional hazards regression models. The optimal cut-off point for transaminases was determined using receiver operating characteristic curves. The 5-year graft survival was calculated after previously excluding the patients with 90-day graft loss. Results. The ALT and AST were risk factors for 90-day graft loss (odds ratio 2.16; 95% CI 1.45-3.23; P < .001 and 2.23; 95% CI 1.55-3.19; P < .001, respectively). The optimal cut-off for ALT and AST in prediction of 90-day graft loss was & GE;1030 and & GE;3899 U/L; area under the curve 0.694 (95% CI 0.602-0.786; P < .001), with 11.3% and 97.1% positive predictive value (PPV) and negative predictive (NPV) value, and 0.673 (95% CI 0.575-0.772; P < .001), with 18.4% PPV and 95.6% NPV, respectively. The activities of AST and ALT on first posttransplant day were not identified as risk factors for late graft loss (P = .924 and P = .629, respectively). Conclusions. Early post-transplant transaminase activities can be used to determine early liver graft loss; however, their utility is lost for assessing the late graft survival.

Skin autofluorescence (SAF) can detect advanced glycation end products (AGEs) that accumulate in tissues over time. AGEs reflect patients’ general health, and their pathological accumulation has been associated with various diseases. This study aimed to determine whether its measurements can correlate with the liver parenchyma quality. This prospective study included 186 patients who underwent liver resections. Liver fibrosis and/or steatosis > 10% were found in almost 30% of the patients. ROC analysis for SAF revealed the optimal cutoff point of 2.4 AU as an independent predictor for macrovesicular steatosis ≥ 10% with an AUC of 0.629 (95% CI 0.538–0.721, p = 0.006), 59.9% sensitivity, 62.4% specificity, and positive (PPV) and negative (NPV) predictive values of 45.7% and 74.1%, respectively. The optimal cutoff point for liver fibrosis was 2.3 AU with an AUC of 0.613 (95% CI 0.519–0.708, p = 0.018), 67.3% sensitivity, 55.2% specificity, and PPV and NPV of 37.1% and 81.2%, respectively. In the multivariable logistic regression model, SAF ≥ 2.4 AU (OR 2.16; 95% CI 1.05–4.43; p = 0.036) and BMI (OR 1.21; 95% CI 1.10–1.33, p < 0.001) were independent predictors of macrovesicular steatosis ≥ 10%. SAF may enhance the available non-invasive methods of detecting hepatic steatosis and fibrosis in patients prior to liver resection.

The use of the Pringle maneuver (PM) varies widely among surgical departments. Its use depends on the operator and type of liver resection. The aim of this study was to determine the impact of the PM on patient outcomes when undergoing major liver resections. This retrospective study comprised 179 colorectal liver metastasis patients from two liver centers from Leeds and Warsaw. Only right or right extended hepatectomies with negative oncological margins were included. The primary outcome measure was the 5-year overall survival (OS). The PM was applied during 60 (33.5%) major hepatectomies included in the study and was associated with a higher peak 3-day postoperative bilirubin concentration (p = 0.002), yet not with the peak 3-day alanine aminotransferase activity (p = 0.415). The 5-year OS after liver resections with the PM and without the PM were 55.0% and 33.4%, respectively (p = 0.019). Following stratification by the Tumor Burden Score, after resections with the use of the PM, superior survival was particularly found in the subgroup of patients at intermediate risk of recurrence (p = 0.004). However, the use of the PM had no significant effect on the 5-year overall survival following adjustment for the confounding effect of the carcinoembryonic antigen concentration (p = 0.265). The use of the PM had no negative effects on the long-term outcomes in patients undergoing major, oncologically radical liver resections for colorectal metastases.

Supplemental Digital Content is available in the text Objective: To compare the early results of mass and layered closure of upper abdominal transverse incisions. Summary of Background Data: Contrary to midline incisions, data on closure of transverse abdominal incisions are lacking. Methods: This is the first analysis of a randomized controlled trial primarily designed to compare mass with layered closure of transverse incisions with respect to incisional hernias. Patients undergoing laparotomy through upper abdominal transverse incisions were randomized to either mass or layered closure with continuous sutures. Incisional surgical site infection (incisional-SSI) was the primary end-point. Secondary end-points comprised suture-to-wound length ratio (SWLR), closure duration, and fascial dehiscence (clinicatrials.gov NCT03561727). Results: A total of 268 patients were randomized to either mass (n=134) or layered (n=134) closure. Incisional-SSIs occurred in 24 (17.9%) and 8 (6.0%) patients after mass and layered closure, respectively (P =0.004), with crude odds ratio (OR) of 0.29 [95% confidence interval (95% CI) 0.13–0.67; P =0.004]. Layered technique was independently associated with fewer incisional-SSIs (OR: 0.29; 95% CI 0.12–0.69; P =0.005). The number needed to treat, absolute, and relative risk reduction for layered technique in reducing incisional-SSIs were 8.4 patients, 11.9%, and 66.5%, respectively. Dehiscence occurred in one (0.8%) patient after layered closure and in two (1.5%) patients after mass closure (P >0.999). Median SWLR were 8.1 and 5.6 (P <0.001) with median closure times of 27.5 and 25.0 minutes (P =0.044) for layered and mass closures, respectively. Conclusions: Layered closure of upper abdominal transverse incisions should be preferred due to lower risk of incisional-SSIs and higher SWLR, despite clinically irrelevant longer duration.

Objective: To compare the early results of mass and layered closure of upper abdominal transverse incisions. Summary of Background Data: Contrary to midline incisions, data on closure of transverse abdominal incisions are lacking. Methods: This is the first analysis of a randomized controlled trial primarily designed to compare mass with layered closure of transverse incisions with respect to incisional hernias. Patients undergoing laparotomy through upper abdominal transverse incisions were randomized to either mass or layered closure with continuous sutures. Incisional surgical site infection (incisional-SSI) was the primary end-point. Secondary end-points comprised suture-to-wound length ratio (SWLR), closure duration, and fascial dehiscence (clinicatrials.gov NCT03561727). Results: A total of 268 patients were randomized to either mass (n=134) or layered (n=134) closure. Incisional-SSIs occurred in 24 (17.9%) and 8 (6.0%) patients after mass and layered closure, respectively (P =0.004), with crude odds ratio (OR) of 0.29 [95% confidence interval (95% CI) 0.13-0.67; P =0.004]. Layered technique was independently associated with fewer incisional-SSIs (OR: 0.29; 95% CI 0.12-0.69; P =0.005). The number needed to treat, absolute, and relative risk reduction for layered technique in reducing incisional-SSIs were 8.4 patients, 11.9%, and 66.5%, respectively. Dehiscence occurred in one (0.8%) patient after layered closure and in two (1.5%) patients after mass closure (P >0.999). Median SWLR were 8.1 and 5.6 (P <0.001) with median closure times of 27.5 and 25.0 minutes (P =0.044) for layered and mass closures, respectively. Conclusions: Layered closure of upper abdominal transverse incisions should be preferred due to lower risk of incisional-SSIs and higher SWLR, despite clinically irrelevant longer duration.