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.

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.

BACKGROUND:Gallstone disease (GD) is common but remains asymptomatic in most cases. However, gallstones can lead to complications like choledocholithiasis or gallbladder cancer. In this study, we analyse the common genetic risk factor for GD, the p.D19H variant in the sterol transporter ABCG8, in Polish patients with gallstones and gallbladder cancer. METHODS:Three adult cohorts were prospectively recruited: 65 patients with gallbladder cancer, 170 obese individuals scheduled for bariatric surgery and 72 patients who underwent endoscopic retrograde cholangiopancreatography due to recurrent choledocholithiasis. The control cohort consisted of 172 gallstone-free adults. The ABCG8 p.D19H (rs11887534) polymorphism was genotyped using TaqMan assays. RESULTS:The minor allele frequency (MAF) of the ABCG8 p.D19H polymorphism was significantly (p = .02) higher among cases with either gallstones or gallbladder cancer (MAF = 8.4%) as compared to controls (MAF = 4.0%). The highest frequency of the risk allele was detected in patients with gallbladder cancer (18.5%) and obese patients with GD (17.5%), followed by individuals with choledocholithiasis (13.9%). Notably, the p.19H variant was associated with an increased risk of developing gallbladder cancer (OR 2.76, 95% CI 1.16-6.54, p = .01) and an increased risk of GD in obese individuals scheduled for bariatric surgery (OR = 2.70, 95% CI 1.05-6.49, p = .03), but did not significantly affect the risk of choledocholithiasis. CONCLUSIONS:The ABCG8 p.D19H common risk variant increases the risk of developing gallbladder cancer in Central Europeans and enhances the risk of gallstones in the obese. Carriers of the p.D19H variant might benefit from personalized preventive strategies, particularly regarding gallbladder cancer.

Background: Glycoprotein-2 (GP2) IgA is a predictor of disease severity in primary sclerosing cholangitis (PSC). We examined GP2 ' s occurrence in the biliary tract, the site of inflammation. Methods: GP2 was analyzed using ELISA, immunoblotting, mass spectrometry, and immunohistochemistry. The samples included: 20 bile and 30 serum samples from PSC patients, 23 bile and 11 serum samples from patients with gallstone disease (GD), 15 bile samples from healthy individuals undergoing liver-donation surgery (HILD), 20 extracts of gallstones (GE) obtained during cholecystectomy, and 101 blood-donor sera. Results: Biliary GP2 concentrations were significantly higher in patients with PSC and GD than in HILD (p < 0.0001). Serum GP2 levels were similar in PSC and GD patients, and controls, but lower than in bile (p < 0.0001). GP2 was detected in all 20 GEs. Mass spectrometry identified GP2 in the bile of 2 randomly selected GD and 2 PSC patients, and in none of 2 HILD samples. GP2 was found in peribiliary glands in 8 out of 12 PSC patients, showing morphological changes in acinar cells, but not in GD-gallbladders. Conclusions: GP2 is present in bile of PSC and GD patients. It is synthesized in the peribiliary glands of PSC patients, supporting a pathogenic role for biliary GP2 in PSC.

Introduction Gallstone disease (GD) is prevalent but typically remains symptom-free. Nevertheless, complications such as choledocholithiasis or gallbladder cancer can arise from gallstones. Both genetic predisposition as well as exogenous factors are known to modulate the gallstone risk. Here we analyse the link between the gallstone-associated variant p.D19H in the hepatobiliary sterol transporter ABCG8 and the development of gallstone-related complications.

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.

Abstract Background Despite inconsistent evidence, international guidelines underline the importance of perioperative hyperoxygenation in prevention of postoperative infections. Further, data on safety and efficacy of this method in liver transplant setting are lacking. The aim was to evaluate efficacy and safety of postoperative hyperoxygenation in prophylaxis of infections after liver transplantation. Methods In this randomized controlled trial, patients undergoing liver transplantation were randomly assigned to either 28% or 80% fraction of inspired oxygen (FiO2) for 6 postoperative hours. Infections occurring during 30-day post-transplant period were the primary outcome measure. Secondary outcome measures included 90-day mortality, 90-day severe morbidity, 30-day pulmonary complications, durations of hospital and intensive care unit stay, and 5-day postoperative bilirubin concentration, alanine and aspartate transaminase activity, and international normalized ratio (INR) (clinicatrials.gov NCT02857855). Results A total of 193 patients were included and randomized to 28% (n = 99) and 80% (n = 94) FiO2. With similar patient, operative, and donor characteristics in both groups, infections occurred in 34.0% (32/94) of patients assigned to 80% FiO2 as compared to 23.2% (23/99) of patients assigned to 28% FiO2 (p = 0.112). Patients randomized to 80% FiO2 more frequently developed severe complications (p = 0.035), stayed longer in the intensive care unit (p = 0.033), and had higher bilirubin concentration over first 5 post-transplant days (p = 0.043). No significant differences were found regarding mortality, duration of hospital stay, pulmonary complications, and 5-day aspartate and alanine transaminase activity and INR. Conclusions Postoperative hyperoxygenation should not be used for prophylaxis of infections after liver transplantation due to the lack of efficacy. Trial registration ClinicalTrials.gov NCT02857855. Registered 7 July 2016.

Hepatocellular carcinoma (HCC) was the third leading cause of cancer-related death globally in 2020. The treatment of the disease is complex, with a high possibility of disease recurrence. The low survival rate of HCC patients is due to their late-stage diagnosis. Hence, the best prognosis is to diagnose HCC at an early stage. The diagnosis of HCC is made through imaging methods and, in selected cases, by biopsy. These diagnostic tools fail for the early detection of HCC. These methods are time-consuming and expensive, especially for resource-limited healthcare settings. Therefore, the development of simple, sensitive, and rapid methods for screening is necessary for the early detection of hepatocellular carcinoma. Tremendous research efforts were made to discover new biomarkers for HCC. Gene mutations, epigenetic modifications, circulating RNA, proteins, circulating tumour cells (CTCs), and circulating tumour-derived exosomes are promising HCC biomarkers that seem to improve diagnosis significantly. On the other hand, various biosensors have provided promising technology for detecting HCC biomarkers through rapid, sensitive, cost-effective, and user-friendly applications. This review summarises the recent studies on serum HCC-based biomarkers and ultrasensitive biosensor technologies, emphasising optical, electrochemical, and mass-signal transduction.

3561 Background: CRC is a complex and heterogeneous disease, with the liver being the most frequent site of metastasis. Around 20% of patients will always progress exclusively in the liver. These patients may be candidates for more aggressive therapeutic procedures that will impact in their outcome. LIVERMET SURVEY Database (LMSD) is a prospective international database, focused on patients operated for CRC liver metastasis, whether resected or not, which purpose is to evaluate patient outcomes and prognostic factors for these resected patients. We propose to analyse all patients enrolled in the (LMSD) to better characterised those determinants that are associated with pLLD. Methods: We analyzed all patients included in the LMSD. Patients with relapse of their disease after the first liver surgery were selected. In order to test associations between hepatic only and extrahepatic metastasis, a univariate and multivariate logistic model was performed with the variables considered clinically more relevant. Imputation of missing data using the mice method (Multivariate Imputation via Chained Equations) was performed. All analyses were performed with R 4.1.1 software. Results: A total of 8715 patients out of 33581 (26%) included in the LMSD presented disease recurrence after a first liver surgery. During their oncological history, pLLD occurred in 1392 patients (16%), and extrahepatic relapse was presented in 7323 patients (84%). The characteristics of patients with pLLD were as follows: 58.4% patients presented synchronic disease, 20.2% had right sided primary tumor, 58.6% presented unilateral disease at time of first hepatic surgery and 20.4% of patients presented R1 surgery. In multivariant analysis, right sided and rectum (HR 0.82. p = 0.001), unilateral liver involvement (HR 0.74, p < 0.001) and > 3cm of diameter in greatest lesion with maximum of 3 lesions (HR 0.85, p = 0.02) were predictive determinants of extrahepatic disease. Only synchronic metastases (HR 1.29, p < 0.001) and male sex (HR 1.15, p = 0.028) were associated with pLLD. Molecular information according to RAS, BRAF and MSI status was not evaluable in a majority of patients since this item has been recently implemented in the questionnaire. Conclusions: This study confirms that about 16% of patients with LLD mCRC will be pLLD mCRC. Despite clinical determinants like synchronic metastatic disease, which is associated with pLLD, further analyses including molecular determinants are needed. Identifying those determinants of pLLD in a scenario where more extreme surgeries and liver transplantations are being considered is a great challenge that needs to be addressed.

A number types of extracellular DNA (eg, cell-free, cfDNA) circulate in human blood, including mitochondrial, transcriptome, and regulatory DNA, usually at low concentrations. Larger amounts of cfDNA appear in any inflammatory condition, including organ damage due to a variety of reasons. The role of cfDNA in solid organ transplantation is discussed in this review as a valuable additional tool in the standard of care of transplant patients. Post-transplant monitoring requires the use of high-quality biomarkers for early detection of graft damage or rejection to be able to apply early therapeutic intervention. CfDNA complements the traditional monitoring strategies, being a risk stratification tool and an important prognostic marker. However, improving the sensitivity and specificity of cfDNA detection is necessary to facilitate personalized patient management, warranting further research in terms of measurement, test standardization, and storage, processing, and shipping. A diagnostic test (Allosure, CareDx, Inc., Brisbane, CA) for kidney, heart and lung transplant patients is now commercially available, and validation for other organs (eg, liver) is pending. To date, donor-derived cfDNA in combination with other biomarkers appears to be a promising tool in graft rejection as it is minimally invasive, time-sensitive, and cost-effective. However, improvement of sensitivity and specificity is required to facilitate personalized patient management. Whether it could be an alternate to graft biopsy remains unclear.

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.