Genetic polymorphisms in interleukin-1β (rs1143634) and interleukin-8 (rs4073) are associated with survival after resection of intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma (iCCA) is a rare, understudied primary hepatic malignancy with dismal outcomes. Aiming to identify prognostically relevant single-nucleotide polymorphisms, we analyzed 11 genetic variants with a role in tumor-promoting inflammation (VEGF, EGF, EGFR, IL-1B, IL-6, CXCL8 (IL-8), IL-10, CXCR1, HIF1A and PTGS2 (COX-2) genes) and their association with disease-free (DFS) and overall survival (OS) in patients undergoing curative-intent surgery for iCCA. Genomic DNA was isolated from 112 patients (64 female, 48 male) with iCCA. Germline polymorphisms were analyzed with polymerase chain reaction-restriction fragment length polymorphism protocols. The IL-1B +3954 C/C (73/112, hazard ratio (HR) = 1.735, p = 0.012) and the IL-8 -251 T/A or A/A (53/112 and 16/112, HR = 2.001 and 1.1777, p = 0.026) genotypes were associated with shorter OS in univariable and multivariable analysis. The IL-1B +3954 polymorphism was also associated with shorter DFS (HR = 1.983, p = 0.012), but this effect was not sustained in the multivariable model. A genetic risk model of 0, 1 and 2 unfavorable alleles was established and confirmed in multivariable analysis. This study supports the prognostic role of the IL-1B C+3954T and the IL-8 T-251A variant as outcome markers in iCCA patients, identifying patient subgroups at higher risk for dismal clinical outcomes

The prognostic impact of preoperative body composition in perihilar and intrahepatic cholangiocarcinoma

Cholangiocarcinoma (CCA) is a rare but highly aggressive malignancy of the biliary system. Although it is amenable to surgical resection in early disease, outcomes are frequently dismal. Here, we investigated the prevalence of body composition (BC) alterations and their prognostic role for surgical patients with intrahepatic (iCCA) and perihilar (pCCA) disease. Patients undergoing curative-intent surgery for iCCA or pCCA between 2010 and 2019 at University Hospital Aachen were included. Axial computed tomography images were retrospectively assessed with a segmentation tool (3D Slicer) at the level of the third lumbar vertebra to determine lumbar skeletal muscle (SM) index, mean SM radiation attenuation, and visceral fat area. The related BC pathologies sarcopenia, myosteatosis, visceral obesity, and sarcopenic obesity were determined using previously described cutoffs. A total of 189 patients (86 with iCCA, 103 with pCCA) were included. Alterations of BC were highly prevalent in iCCA and pCCA, respectively: sarcopenia, 33% (28/86) and 39% (40/103); myosteatosis, 66% (57/86) and 66% (68/103); visceral obesity, 56% (48/86) and 67% (69/103); sarcopenic obesity, 11% (9/86) and 17% (17/103). Sarcopenia and myosteatosis did not have a significant prognostic role for disease-free survival (DFS) and overall survival (OS). Patients with iCCA with sarcopenic obesity (n = 9) had significantly shorter OS than patients without sarcopenic obesity (n = 7; log-rank p = 0.002; median OS, 11 months and 31 months; 1-year mortality, 55.6% [5/9] and 22% [17/77]; 5-year mortality, 88.9% [8/9] and 61% [47/77], respectively). In multivariable analysis, only tumor-related risk factors remained prognostic for DFS and OS. Sarcopenic obesity may affect clinical outcomes after curative-intent surgery for iCCA, indicating that imaging-based analysis of BC may hold prognostic value for long-term survival and could aid preoperative patient selection

Prognostic Factors for Mortality in Acute Mesenteric Ischemia.

Postoperative mortality in patients undergoing surgical and/or interventional treatment for acute mesenteric ischemia (AMI) has remained an unsolved problem in recent decades. Here, we investigated clinical predictors of postoperative mortality in a large European cohort of patients undergoing treatment for AMI. In total, 179 patients who underwent surgical and/or interventional treatment for AMI between 2009 and 2021 at our institution were included in this analysis. Associations between postoperative mortality and various clinical variables were assessed using univariate and multivariable binary logistic regression analysis. Most of the patients were diagnosed with arterial ischemia (AI; n = 104), while venous ischemia (VI; n = 21) and non-occlusive mesenteric ischemia (NOMI; n = 54) were present in a subset of patients. Overall inhouse mortality was 55.9% (100/179). Multivariable analyses identified leukocytes (HR = 1.08; p = 0.008), lactate (HR = 1.25; p = 0.01), bilirubin (HR = 2.05; p = 0.045), creatinine (HR = 1.48; p = 0.039), etiology (AI, VI or NOMI; p = 0.038) and portomesenteric vein gas (PMVG; HR = 23.02; p = 0.012) as independent predictors of postoperative mortality. In a subanalysis excluding patients with fatal prognosis at the first surgical exploration (n = 24), leukocytes (HR = 1.09; p = 0.004), lactate (HR = 1.27; p = 0.003), etiology (AI, VI or NOMI; p = 0.006), PMVG (HR = 17.02; p = 0.018) and intraoperative FFP transfusion (HR = 4.4; p = 0.025) were determined as independent predictors of postoperative mortality. Further, the risk of fatal outcome changed disproportionally with increased preoperative lactate values. The clinical outcome of patients with AMI was determined using a combination of pre- and intraoperative clinical and radiological characteristics. Serum lactate appears to be of major clinical importance as the risk of fatal outcome increases significantly with higher lactate values

Impact of Angiogenesis- and Hypoxia-Associated Polymorphisms on Tumor Recurrence in Patients with Hepatocellular Carcinoma Undergoing Surgical Resection

Simple Summary: Hepatocellular carcinoma remains a leading cause of cancer-related death and the most common primary hepatic malignancy in the Western hemisphere. Previous research found that angiogenesis-related cytokines and elevated levels of interleukin 8 and vascular endothelial growth factor (VEGF) shorten the expected time of survival. Moreover, factors of tumor angiogenesis- and hypoxia-driven signaling pathways are already associated with worse outcome in disease-free survival in several tumor entities. Our study investigates the prognosis of hepatocellular carcinoma patients based on a selection of ten different single-nucleotide polymorphisms from angiogenesis, carcinogenesis, and hypoxia pathways. Our study with 127 patients found supporting evidence that polymorphisms in angiogenesis-associated pathways corelate with disease-free survival and clinical outcome in patients with hepatocellular carcinoma. Abstract: Tumor angiogenesis plays a pivotal role in hepatocellular carcinoma (HCC) biology. Identifying molecular prognostic markers is critical to further improve treatment selection in these patients. The present study analyzed a subset of 10 germline polymorphisms involved in tumor angiogenesis pathways and their impact on prognosis in HCC patients undergoing partial hepatectomy in a curative intent. Formalin-fixed paraffin-embedded (FFPE) tissues were obtained from 127 HCC patients at a German primary care hospital. Genomic DNA was extracted, and genotyping was carried out using polymerase chain reaction (PCR)-restriction fragment length polymorphism-based protocols. Polymorphisms in interleukin-8 (IL-8) (rs4073; p = 0.047, log-rank test) and vascular endothelial growth factor (VEGF C + 936T) (rs3025039; p = 0.045, log-rank test) were significantly associated with disease-free survival (DFS). After adjusting for covariates in the multivariable model, IL-8 T-251A (rs4073) (adjusted p = 0.010) and a combination of "high-expression" variants of rs4073 and rs3025039 (adjusted p = 0.034) remained significantly associated with DFS. High-expression variants of IL-8 T-251A may serve as an independent molecular marker of prognosis in patients undergoing surgical resection for HCC. Assessment of the patients' individual genetic risks may help to identify patient subgroups at high risk for recurrence following curative-intent surgery

Four Decades of Clinical Liver Transplantation Research:Results of a Comprehensive Bibliometric Analysis

BACKGROUND: Nearly 40 y have passed since the 1983 National Institutes of Health Consensus-Development-Conference, which has turned liver transplantation (LT) from a clinical experiment into a routine therapeutic modality. Since' clinical LT has changed substantially. We aimed to comprehensively analyze the publication trends in the most-cited top-notch literature in LT science over a 4-decade period.METHODS: A total of 106 523 items were identified between January 1981 and May 2021 from the Web of Science Core Collection. The top 100 articles published were selected using 2 distinct citation-based strategies to minimize bias. Various bibliometric tools were used for data synthesis and visualization.RESULTS: The citation count for the final dataset of the top 100 articles ranged from 251 to 4721. Most articles were published by US authors (n = 61). The most prolific institution was the University of Pittsburgh (n = 15). The highest number of articles was published in Annals of Surgery, Hepatology, and Transplantation; however, Hepatology publications resulted in the highest cumulative citation of 9668. Only 10% of the articles were classified as evidence level 1. Over 90% of first/last authors were male. Our data depict the evolution of research focus over 40 y. In part, a disproportional flow of citations was observed toward already well-cited articles. This might also project a slowed canonical progress, which was described in other fields of science.CONCLUSIONS: This study highlights key trends based on a large dataset of the most-cited articles over a 4-decade period. The present analysis not only provides an important cross-sectional and forward-looking guidance to clinicians, funding bodies, and researchers but also draws attention to important socio-academic or demographic aspects in LT.</p

Eosinophils Attenuate Hepatic Ischemia-Reperfusion Injury in Mice Through ST2-Dependent Il-13 Production

Eosinophils are a myeloid cell subpopulation that mediates type 2 T helper cell immune responses. Unexpectedly, we identified a rapid accumulation of eosinophils in 22 human liver grafts after hepatic transplantation. In contrast, no eosinophils were detectable in healthy liver tissues before transplantation. Studies with two genetic mouse models of eosinophil deficiency and a mouse model of antibody-mediated eosinophil depletion revealed exacerbated liver injury after hepatic ischemia and reperfusion. Adoptive transfer of bone marrow-derived eosinophils normalized liver injury of eosinophil-deficient mice and reduced hepatic ischemia and reperfusion injury in wild-type mice. Mechanistic studies combining genetic and adoptive transfer approaches identified a critical role of suppression of tumorigenicity (ST2)-dependent production of interleukin-13 by eosinophils in the hepatoprotection against ischemia-reperfusion-induced injury. Together, these data provide insight into a mechanism of eosinophil-mediated liver protection that could serve as a therapeutic target to improve outcomes of patients undergoing liver transplantation

Deceased donor liver utilisation and assessment:Consensus guidelines from the European Liver and Intestine Transplant Association

Over the past two decades, the application of machine perfusion (MP) in human liver transplantation has moved from the realm of clinical exploration to routine clinical practice. Both in situ and ex situ perfusion strategies are feasible, safe, and may offer improvements in relevant post-transplant outcomes. An important utility of these strategies is the ability to transplant grafts traditionally considered too risky to transplant using conventional cold storage alone. While dynamic assessment and ultimately transplantation of such livers is an important goal for the international liver transplant community, its clinical application is inconsistent. To this end, ELITA (the European Liver and Intestine Transplant Association) gathered a panel of experts to create consensus guidelines regarding selection, approach, and criteria for deceased donor liver assessment in the MP era. An eight-member steering committee (SC) convened a panel of 44 professionals working in 14 countries in Europe and North America. The SC identified topics related to liver utilisation and assessment for transplantation. For each topic, subtopics were created to answer specific clinical questions. A systematic literature review was performed, and the panel graded relevant evidence. The SC drafted initial statements addressing each clinical question. Statements were presented at the in-person Consensus Meeting on Liver Discard and Viability Assessment during the ELITA Summit held from April 19-20, 2024, in Madrid, Spain. Online voting was held to approve statements according to a modified Delphi method; statements reaching ≥85% agreement were approved. Statements addressing liver utilisation, the definition of high-risk livers, and strategies and criteria for dynamic liver assessment are presented.</p

Outcomes of elective liver surgery worldwide: a global, prospective, multicenter, cross-sectional study

Background: The outcomes of liver surgery worldwide remain unknown. The true population-based outcomes are likely different to those vastly reported that reflect the activity of highly specialized academic centers. The aim of this study was to measure the true worldwide practice of liver surgery and associated outcomes by recruiting from centers across the globe. The geographic distribution of liver surgery activity and complexity was also evaluated to further understand variations in outcomes. Methods: LiverGroup.org was an international, prospective, multicenter, cross-sectional study following the Global Surgery Collaborative Snapshot Research approach with a 3-month prospective, consecutive patient enrollment within January–December 2019. Each patient was followed up for 90 days postoperatively. All patients undergoing liver surgery at their respective centers were eligible for study inclusion. Basic demographics, patient and operation characteristics were collected. Morbidity was recorded according to the Clavien–Dindo Classification of Surgical Complications. Country-based and hospital-based data were collected, including the Human Development Index (HDI). (NCT03768141). Results: A total of 2159 patients were included from six continents. Surgery was performed for cancer in 1785 (83%) patients. Of all patients, 912 (42%) experienced a postoperative complication of any severity, while the major complication rate was 16% (341/2159). The overall 90-day mortality rate after liver surgery was 3.8% (82/2,159). The overall failure to rescue rate was 11% (82/ 722) ranging from 5 to 35% among the higher and lower HDI groups, respectively. Conclusions: This is the first to our knowledge global surgery study specifically designed and conducted for specialized liver surgery. The authors identified failure to rescue as a significant potentially modifiable factor for mortality after liver surgery, mostly related to lower Human Development Index countries. Members of the LiverGroup.org network could now work together to develop quality improvement collaboratives

New Frontiers in Organ Preservation and Hepatoprotection

This editorial aims to summarize the 13 scientific articles published in the Special Issue entitled “New Frontiers in Organ Preservation and Hepatoprotection” [...]</jats:p