Internal and external validation of indocyanine green plasma disappearance rate to discard liver grafts before procurement.

Backgrounds/Aims: Thirty percent of liver grafts in donors after brain death (DBD) in Spain are rejected by procurement surgeons owing to marginal graft quality. Poor donor indocyanine green (ICG) clearance has been associated with graft discard and malfunction. This study aimed to internally and externally validate the predictive value of ICG-plasma disappearance rate (ICG-PDR) to reject grafts before donation and set a cut-off to avoid missing any potential effective donors. Methods: Between March 2017 and August 2023, ICG clearance test was performed immediately before procurement in 71 DBD. The surgeon was blinded to test results. Univariate and multivariate analyses were performed to detect independent predictors of graft discard. Discrimination and calibration of predictors were assessed and a cut-off with 100% specificity was set. External validation was performed on 17 donors evaluated by three other transplantation teams. Results: In the training cohort, 30 of 71 grafts were discarded for transplantation. ICG-PDR was the only donor variable independently associated with graft discard. The area under receiver operating characteristic curve for ICG-PDR was 0.875 (95% confidence interval: 0.768-0.947) and good calibration was observed. Below a PDR of 13.5%/min, no graft was accepted for transplantation. These results were successfully validated using the external cohort of donors. Conclusions: ICG clearance test performed in DBD was internally and externally validated to predict liver graft discard. It could be used as a screening tool before donation to avoid unnecessary costs of travel and human resources.

Critical appraisal of surgical margins according to KRAS status in liver resection for colorectal liver metastases: Should surgical strategy be influenced by tumor biology?

BACKGROUND: KRAS mutation is a negative prognostic factor for colorectal liver metastases. Several studies have investigated the resection margins according to KRAS status, with conflicting results. The aim of the study was to assess the oncologic outcomes of R0 and R1 resections for colorectal liver metastases according to KRAS status. METHODS: All patients who underwent resection for colorectal liver metastases between 2010 and 2015 with available KRAS status were enrolled in this multicentric international cohort study. Logistic regression models were used to investigate the outcomes of R0 and R1 colorectal liver metastases resections according to KRAS status: wild type versus mutated. The primary outcomes were overall survival and disease-free survival. RESULTS: The analysis included 593 patients. KRAS mutation was associated with shorter overall survival (40 vs 60 months; P = .0012) and disease-free survival (15 vs 21 months; P = .003). In KRAS-mutated tumors, the resection margin did not influence oncologic outcomes. In multivariable analysis, the only predictor of disease-free survival and overall survival was primary tumor location (P = .03 and P = .03, respectively). In KRAS wild-type tumors, R0 resection was associated with prolonged overall survival (74 vs 45 months, P < .001) and disease-free survival (30 vs 17 months, P < .001). The multivariable model confirmed that R0 resection margin was associated with prolonged overall survival (hazard ratio = 1.43, 95% confidence interval: 1.01-2.03) and disease-free survival (hazard ratio = 1.42; 95% confidence interval: 1.06-1.91). CONCLUSIONS: KRAS-mutated colorectal liver metastases showed more aggressive tumor biology with inferior overall survival and disease-free survival after liver resection. Although R0 resection was not associated with improved oncologic outcomes in the KRAS-mutated tumors group, it seems to be of paramount importance for achieving prolonged long-term survival in KRAS wild-type tumors.

High rate of species misidentification reduces the taxonomic certainty of European biodiversity databases of ivies (Hedera L.).

The digitization of natural history specimens and the popularization of citizen science are creating an unprecedented availability of large amounts of biodiversity data. These biodiversity inventories can be severely affected by species misidentification, a source of taxonomic uncertainty that is rarely acknowledged in biodiversity data management. For these reasons, taxonomists debate the use of online repositories to address biological questions at the species level. Hedera L. (ivies) provides an excellent case study as it is well represented in both herbaria and online repositories with thousands of records likely to be affected by high taxonomic uncertainty. We analyze the sources and extent of taxonomic errors in the identification of the European ivy species by reviewing herbarium specimens and find a high misidentification rate (18% on average), which varies between species (maximized in H. hibernica: 55%; H. azorica: 48%; H. iberica: 36%) and regions (maximized in the UK: 38% and Spain: 27%). We find a systematic misidentification of all European ivies with H. helix behind the high misidentification rates in herbaria and warn of even higher rates in online records. We compile a spatial database to overcome the large discrepancies we observed in species distributions between online and morphologically reviewed records.

Antiproliferative in Vitro Evaluation of Terpenic Amines Synthesized via a Rhodium-catalyzed Hydroaminomethylation.

Terpene-derived alkaloids show a variety of biological activities, including antioxidant, anti-inflammatory, antimicrobial and cytotoxicity effects. In this work, homologated monoterpene amines have been prepared via a rhodium-catalyzed hydroaminomethylation of biomass-based alkenes, such as (R)-limonene, linalool, myrcene and camphene, in combination with secondary amines of aliphatic and aromatic nature, namely morpholine and N-methylaniline, leading to highly chemo- and regioselective processes. The as-prepared amines were obtained in 50-99 % overall yields, and in vitro tested on a human colon cancer cell line (HCT-116) to evaluate their cytotoxic potential. The lead compound of the series (3 a) showed cytotoxicity in the micromolar range (IC50 52.46 µM) via the induction of cell death by apoptosis, paving the way towards further structure-activity relationship studies.

Repeated pancreatic resection for pancreatic metastases from renal cell Carcinoma: A Spanish multicenter study (PANMEKID).

BACKGROUND AND OBJECTIVES: Recurrent isolated pancreatic metastasis from Renal Cell Carcinoma (RCC) after pancreatic resection is rare. The purpose of our study is to describe a series of cases of relapse of pancreatic metastasis from renal cancer in the pancreatic remnant and its surgical treatment with a repeated pancreatic resection, and to analyse the results of both overall and disease-free survival. METHODS: Multicenter retrospective study of patients undergoing pancreatic resection for RCC pancreatic metastases, from January 2010 to May 2020. Patients were grouped into two groups depending on whether they received a single pancreatic resection (SPS) or iterative pancreatic resection. Data on short and long-term outcome after pancreatic resection were collected. RESULTS: The study included 131 pancreatic resections performed in 116 patients. Thus, iterative pancreatic surgery (IPS) was performed in 15 patients. The mean length of time between the first pancreatic surgery and the second was 48.9 months (95 % CI: 22.2-56.9). There were no differences in the rate of postoperative complications. The DFS rates at 1, 3 and 5 years were 86 %, 78 % and 78 % vs 75 %, 50 % and 37 % in the IPS and SPS group respectively (p = 0.179). OS rates at 1, 3, 5 and 7 years were 100 %, 100 %, 100 % and 75 % in the IPS group vs 95 %, 85 %, 80 % and 68 % in the SPS group (p = 0.895). CONCLUSION: Repeated pancreatic resection in case of relapse of pancreatic metastasis of RCC in the pancreatic remnant is justified, since it achieves OS results similar to those obtained after the first resection.

Application of Biostimulant in Seeds and Soil on Three Chickpea Varieties: Impacts on Germination, Vegetative Development, and Bacterial Facilitation of Nitrogen and Phosphorus.

Chickpeas (Cicer arietinum L.) are a valuable legume crop due to their nutritional value. To maintain chickpea productivity and avoid the adverse effects of climate change on soil and plant processes, it is crucial to address demand. Achieving this necessitates implementing sustainable agricultural practices incorporating the use of biostimulants, adaptable crops for arid conditions, as well as pest and disease-resistant crops that are sustainable over time. Three varieties of chickpeas were analysed to determine the effect of two different biostimulant application methods on both germination and vegetative growth. Possible effects due to location were also examined by conducting tests at two different sites. Significant variations in biostimulant response were evident only during the germination period, but not during the vegetative development stage, where the observed statistical differences were influenced more by the location or variety of chickpeas employed. Furthermore, this study examined the effect of biostimulants on nutrient cycling within the soil-plant microbiota system. Nitrogen-fixing bacteria (NFB) are present in the soil of chickpea crops at an order of magnitude of 107 CFU/g DS. Additionally, an average concentration of 106 CFU/g DS of phosphorus-mobilising bacteria was observed. Applying biostimulants (BioE) to seeds resulted in a successful germination percentage (GP) for both Amelia (AM) and IMIDRA 10 (IM) varieties.

Is spleen-preserving surgery safe for abdominal trauma?

BACKGROUND: Treatment of splenic trauma is currently based on non-surgical treatment or the use of interventional radiology. The conservative surgery of the spleen in splenic trauma remains marginal. OBJECTIVE: To analyze the safety and efficacy of conservative surgical treatment in splenic trauma. METHOD: A retrospective study was performed over a 16-year period with the intention of recording the diagnostic and therapeutic attitude in a second level hospital, focusing on patients who received conservative splenic surgical treatment for splenic trauma, excluding splenectomies and non-surgical treatment. RESULTS: 110 patients presented splenic trauma. Spleen-sparing surgery was performed in 15 patients. The grades of splenic lesions were: 1 patient with grade I, 1 patient with grade II, 7 patients with grade III and 6 patients with grade IV. Surgical treatment was splenorrhaphy in 5 patients (33%), hemostatic agents and polyglycolic acid mesh in 4 (26%), partial splenectomy with placement of polyglycolic acid mesh in 3 (20%), partial splenectomy in 2 (13%), and electrocautery in 1 (6%). None of the patients initially treated with conservative surgery required posterior splenectomy and no patient died. CONCLUSION: We provide evidence supporting the usefulness and safety of conservative splenic surgery in splenic trauma, which would have its place in grades II, III and IV trauma in health centers that do not have urgent interventional radiology.

ANTECEDENTES: El tratamiento del traumatismo esplénico se basa en medidas conservadoras no quirúrgicas o en el uso de radiología intervencionista. La cirugía conservadora del bazo en el traumatismo esplénico sigue siendo inusual. OBJETIVO: El análisis de seguridad y eficacia del tratamiento quirurgico conservador en el traumatismo esplénico. MÉTODO: Se realizó un estudio retrospectivo durante un período de 16 años con la intención de registrar la actitud diagnóstica y terapéutica en un hospital de segundo nivel, enfocándose en los pacientes que recibieron tratamiento quirúrgico conservador esplénico por traumatismo esplénico, excluyendo esplenectomías y tratamientos no quirúrgicos. RESULTADOS: 110 pacientes presentaron traumatismo esplénico. La cirugía conservadora esplénica se realizó en 15 pacientes. Los grados de lesiones esplénicas fueron: 1 paciente con grado I, 1 paciente con grado II, 7 pacientes con grado III y 6 pacientes con grado IV. El tratamiento quirúrgico fue esplenorrafia en 5 pacientes (33%), agentes hemostáticos y malla de ácido poliglicólico en 4 (26%), esplenectomía parcial con colocación de malla de ácido poliglicólico en 3 (20%), esplenectomía parcial en 2 (13%) y hemostasia con electrocauterio en 1 (6%). Ninguno de los pacientes tratados inicialmente con cirugía conservadora requirió esplenectomía posterior y ningún paciente falleció. CONCLUSIONES: La cirugía conservadora esplénica puede ser útil y segura en traumatismos esplénicos, la cual tendría su lugar en traumatismos de grados II, III y IV en centros hospitalarios en los que no se cuente con radiología intervencionista urgente.

Lupus anticoagulant hypoprothrombinemia syndrome: A case report.

Lupus anticoagulant hypoprothrombinemia syndrome (LAHPS) is a rare entity associated with an increased risk of hemorrhage. Corticosteroids have been used in its treatment with favorable results. We present the case of a 54-year-old female patient with a personal history of Lupus diagnosed with LAHPS following an episode of cerebellar hemorrhage.

Ustekinumab and vedolizumab for the prevention of postoperative recurrence of Crohn's disease: Results from the ENEIDA registry.

BACKGROUND: Anti-TNF agents are the only effective biological agents for the prevention of postoperative recurrence (POR) in Crohn's disease (CD). However, they are contraindicated or have been shown to fail in some patients. Although ustekinumab and vedolizumab were licensed for CD some years ago, data in this setting are scarce. METHODS: All CD patients in whom ustekinumab or vedolizumab was prescribed for the prevention of POR within three months of ileocolonic resection with anastomosis were identified from the ENEIDA registry. The development of endoscopic, clinical and surgical POR was registered. RESULTS: Forty patients were treated for the prevention of POR with ustekinumab and 25 were treated with vedolizumab. Eighty per cent had at least one risk factor for POR (prior resections, active smoking, perianal disease or penetrating disease behaviour). All the patients had been exposed to anti-TNF therapy. After a median follow-up of 17 and 26 months, the cumulative probability of clinical POR at 12 months after surgery was 32% and 30% for ustekinumab and vedolizumab, respectively. Endoscopic assessment within the first 18 months after surgery was available for 80% of the patients on ustekinumab and 70% for those on vedolizumab. The rate of endoscopic POR was 42% for ustekinumab and 40% for vedolizumab. One patient treated with ustekinumab and two with vedolizumab underwent a new intestinal resection. CONCLUSIONS: Ustekinumab and vedolizumab seem to be effective in the prevention of POR in patients at high risk. Our results warrant controlled trials comparing these drugs with conventional therapies.

Climatic niche pre-adaptation facilitated island colonization followed by budding speciation in the Madeiran ivy (Hedera maderensis, Araliaceae).

The path followed by species in the colonization of remote oceanic islands ultimately depends on their phylogenetic constraints and ecological responses. In this study, we aim to evaluate the relative role of geographical and ecological forces in the origin and evolution of the Madeiran ivy (Hedera maderensis), a single-species endemic belonging to the western polyploid clade of Hedera. To determine the phylogenetic placement of H. maderensis within the western polyploid clade, we analyzed 40 populations (92 individuals) using genotyping-by-sequencing and including Hedera helix as outgroup. Climatic niche differences among the study species were evaluated using a database with 867 records representing the entire species ranges. To test species responses to climate, 13 vegetative and reproductive functional traits were examined for 70 populations (335 individuals). Phylogenomic results revealed a nested pattern with H. maderensis embedded within the south-western Iberian H. iberica. Gradual niche differentiation from the coldest and most continental populations of H. iberica to the warm and stable coastal population sister to H. maderensis parallels the geographical pattern observed in the phylogeny. Similarity in functional traits is observed for H. maderensis and H. iberica. The two species show leaves with higher specific leaf area (SLA), lower leaf dry matter content (LDMC) and thickness and fruits with lower pulp fraction than the other western polyploid species H. hibernica. Acquisition of a Macaronesian climatic niche and the associated functional syndrome in mainland European ivies (leaves with high SLA, and low LDMC and thickness, and fruits with less pulp content) was a key step in the colonization of Madeira by the H. iberica/H. maderensis lineage, which points to climatic pre-adaptation as key in the success of island colonization (dispersal and establishment). Once in Madeira, budding speciation was driven by geographical isolation, while ecological processes are regarded as secondary forces with a putative impact in the lack of further in situ diversification.

Bile acid-induced lung injury: update of reverse translational biology.

The presence of bile acids in lung tissue is associated with some clinical features observed in various medical specialties, but it took time to understand that these are due to a "bile acid-induced lung injury" since specific translational studies and cross-disciplinary awareness were lacking. We used a reverse translational approach to update and summarize the current knowledge about the mechanisms of bile acid-induced lung injury. This has been done in a cross-disciplinary fashion since these conditions may occur in patients of various ages and in different medical fields. We here define these clinical conditions, then we review the physiopathology of these conditions and the animal models used to mimic them, and, finally, their pathobiology. Mechanisms of bile acid-induced lung injury have been partially clarified over time and are represented by 1) the interaction with secretory phospholipase A2 pathway, 2) the effect on surfactant function and structure, 3) the biological effects on inflammation and local immunity, and 4) the direct cellular toxicity. These mechanisms are schematically illustrated and histological comparisons between acute respiratory distress syndrome (ARDS) induced by bile acids and other triggers are also provided. Based on these mechanisms, we propose possible direct therapeutic applications and, finally, we discuss further research steps to improve the understanding of processes that generate pathological clinical conditions.

Long-Term Outcomes of Perioperative Versus Neoadjuvant Chemotherapy for Resectable Colorectal Liver Metastases: An International Multicentre Propensity-Score Matched Analysis with Stratification by Contemporary Risk-Scoring.

BACKGROUND: There is still debate regarding the principal role and ideal timing of perioperative chemotherapy (CTx) for patients with upfront resectable colorectal liver metastases (CRLM). This study assesses long-term oncological outcomes in patients receiving neoadjuvant CTx only versus those receiving neoadjuvant combined with adjuvant therapy (perioperative CTx). METHODS: International multicentre retrospective analysis of patients with CRLM undergoing liver resection between 2010 and 2015. Characteristics and outcomes were compared before and after propensity score matching (PSM). Primary endpoints were long-term oncological outcomes, such as recurrence-free survival (RFS) and overall survival (OS). Furthermore, stratification by the tumour burden score (TBS) was applied. RESULTS: Of 967 patients undergoing hepatectomy, 252 were analysed, with a median follow-up of 45 months. The unmatched comparison revealed a bias towards patients with neoadjuvant CTx presenting with more high-risk patients (p = 0.045) and experiencing increased postoperative complications ≥Clavien-Dindo III (20.9% vs. 8%, p = 0.003). Multivariable analysis showed that perioperative CTx was associated with significantly improved RFS (hazard ratio [HR] 0.579, 95% confidence interval [CI] 0.420-0.800, p = 0.001) and OS (HR 0.579, 95% CI 0.403-0.834, p = 0.003). After PSM (n = 180 patients), the two groups were comparable regarding baseline characteristics. The perioperative CTx group presented with a significantly prolonged RFS (HR 0.53, 95% CI 0.37-0.76, p = 0.007) and OS (HR 0.58, 95% CI 0.38-0.87, p = 0.010) in both low and high TBS patients. CONCLUSIONS: When patients after resection of CRLM are able to tolerate additional postoperative CTx, a perioperative strategy demonstrates increased RFS and OS in comparison with neoadjuvant CTx only in both low and high-risk situations.

Liver resection in elderly patients with extensive CRLM: Are we offering an adequate treatment? A propensity score matched analysis.

BACKGROUND: Data on the management of elderly patients with extensive colorectal liver metastases (CRLM) are scarce and conflicting. This study assesses differences in management and long-term oncological outcomes between older and younger patients with CRLM and a high Tumour Burden Score (TBS). METHODS: International multicentre retrospective study on patients with CRLM and a category 3 TBS, submitted to liver resection. Patients were divided into two groups according to their age (younger and older than 75) and were compared using propensity score matching (PSM) analysis and multivariable regression models. Differences in management and oncological outcomes including recurrence-free survival (RFS) and overall survival (OS) were assessed. RESULTS: The study included 386 patients, median follow-up was 48 months. The unmatched comparison revealed a higher ASA score (p = 0.035), less synchronous CRLM (47% vs 68%, p = 0.003), a lower median number of lesions (1 vs 3, p = 0.004) and less perioperative chemotherapy (CTx) (66% vs 88%, p < 0.001) in the elderly group. Despite the absence of CTx being an independent predictor of decreased RFS and OS (HR 0.760, p = 0.044 and HR 0.719, p = 0.049, respectively), the elderly group still received less CTx (OR 0.317, p = 0.001) than the younger group. After PSM (n = 100 patients), the two groups were comparable, however, CTx administration was still significantly lower in the elderly group. CONCLUSION: Liver resection should be considered in patients aged 75 and older, even if they present with extensive liver disease. Despite CTx being associated with improved oncological outcomes, a large percentage of elderly patients with CRLM are undertreated.

Liver metastases of a malignant solitary fibrous tumor: the important role of immunohistochemistry in this rare entity.

Solitary fibrous tumor (SFT) is a rare neoplasm of mesenchymal origin that normally appears in the pleura; however, it has been described in other extrapleural locations. This tumor is rarely malignant and only a few cases of metastatic SFT have been described.

Improving Matching Between Recipient and Donor in Liver Transplantation: Are Scores Able to Predict Long-term Survival?

BACKGROUND: The primary goal was to calculate the value of delta Model for End-Stage Liver Disease (D-MELD) and Balance of Risk (BAR) scores in patients who underwent liver transplant. The secondary objective was to evaluate D-MELD and BAR scores' ability to predict patient and graft survival. METHODS: We retrospectively evaluated 336 patients who underwent liver transplant in a tertiary medical center between January 2010 and December 2020. The D-MELD and the BAR scores were evaluated through a receiver operating characteristic curve with the calculation of area under the curve (AUC) to evaluate the predictive score power for 3-month, 6-month, 1-year, and 5-year patient and graft survivals. RESULTS: The AUCs of D-MELD score in predicting 5-year patient and graft survival were 0.506 (95% CI, 0.43-0.57) and 0.49 (95% CI, 0.42-0.56), respectively. The AUCs of BAR score in predicting 5-year patient and graft survival were 0.50 (95% CI, 0.33-0.66) and 0.49 (95% CI, 0.30-0.67), respectively. CONCLUSIONS: We could not confirm the ability to predict long-term survival by using D-MELD and BAR scores in our sample; however, there is a statistically significant trend in receiver operating characteristic curves of 5-year patient and graft survivals. We encourage the use of new scoring systems with a greater external validation to improve allograft allocation.

Pancreatic metastases from renal cell carcinoma. Postoperative outcome after surgical treatment in a Spanish multicenter study (PANMEKID).

BACKGROUND: Renal Cell Carcinoma (RCC) occasionally spreads to the pancreas. The purpose of our study is to evaluate the short and long-term results of a multicenter series in order to determine the effect of surgical treatment on the prognosis of these patients. METHODS: Multicenter retrospective study of patients undergoing surgery for RCC pancreatic metastases, from January 2010 to May 2020. Variables related to the primary tumor, demographics, clinical characteristics of metastasis, location in the pancreas, type of pancreatic resection performed and data on short and long-term evolution after pancreatic resection were collected. RESULTS: The study included 116 patients. The mean time between nephrectomy and pancreatic metastases' resection was 87.35 months (ICR: 1.51-332.55). Distal pancreatectomy was the most performed technique employed (50 %). Postoperative morbidity was observed in 60.9 % of cases (Clavien-Dindo greater than IIIa in 14 %). The median follow-up time was 43 months (13-78). Overall survival (OS) rates at 1, 3, and 5 years were 96 %, 88 %, and 83 %, respectively. The disease-free survival (DFS) rate at 1, 3, and 5 years was 73 %, 49 %, and 35 %, respectively. Significant prognostic factors of relapse were a disease free interval of less than 10 years (2.05 [1.13-3.72], p 0.02) and a history of previous extrapancreatic metastasis (2.44 [1.22-4.86], p 0.01). CONCLUSIONS: Pancreatic resection if metastatic RCC is found in the pancreas is warranted to achieve higher overall survival and disease-free survival, even if extrapancreatic metastases were previously removed. The existence of intrapancreatic multifocal compromise does not always warrant the performance of a total pancreatectomy in order to improve survival.

Inter-laboratory validation of an ISO test method for measuring enzyme activities in soil samples using colorimetric substrates.

The evaluation of soil quality requires the use of robust methods to assess biologically based indicators. Among them, enzyme activities are used for several decades, but there is a clear need to update their measurement methods for routine use, in combining feasibility, accuracy, and reliability. To this end, the platform Biochem-Env optimized a miniaturized method to measure enzyme activities in soils using colorimetric substrates in micro-well plates. The standardization of the method was carried out within the framework of ISO/TC 190/SC 4/WG 4 "Soil quality - Biological methods" workgroup, recommending an inter-laboratory evaluation for the publication of a full ISO standard. That evaluation, managed by the platform, was based on the measurement, in six soils of contrasted physicochemical properties, of the ten soil enzyme activities described in the standard. Eight laboratories were involved in the validation study. Only 2.7% of outliers were identified from the analyses of the whole dataset. The repeatability and reproducibility of the method were determined by computing, respectively, the intra-laboratory (CVr,) and inter-laboratory (CVR) coefficients of variation for each soil and enzyme. The mean CVr ranged from 4.5% (unbuffered phosphatase) to 9.9% (α-glucosidase), illustrating a reduced variability of enzyme activities within laboratories. The mean CVR ranged from 13.8% (alkaline phosphatase) to 30.9% (unbuffered phosphatase). Despite this large CVR noticed for unbuffered phosphatase, the method was repeatable, reproducible, and sensitive. It also proved to be applicable for measuring enzyme activities in different types of soils. These results have been found successful by ISO/TC 190/SC4 and resulted in the publication of ISO 20130:2018 standard.

Liver Transplantation in Patients With Hepatocellular Carcinoma: Long-Term Survival Results.

BACKGROUND: Liver transplant (LT) is the treatment of choice for patients diagnosed with hepatocellular carcinoma (HCC) within the Milan criteria. Its applicability is limited by the risk for recurrence and the impact on waiting lists. We aimed to describe our results in patients with LT due to HCC and to evaluate its long-term survival outcomes. METHODS: A retrospective observational study was carried out on all patients undergoing LT between January 2010 and December 2020. RESULTS: Among 336 patients undergoing LT, 99 had early-stage HCC with underlying cirrhosis in 93.9%. Average time from HCC diagnosis to transplant was 161 days [99-248 days]. In this period, 91 (91.9%) patients received adjuvant treatment. Seven (7.1%) of 99 patients had HCC recurrence and 33 (33.3%) died during the follow-up period. In terms of survival, LT in patients with and without HCC resulted in 6-month survival of 87.9% and 84.3%, 1-year patient survival of 84.7% and 79.4%, 3-year survival rate of 71.2% and 70.6%, and 5-year survival rate of 64.6% and 65.3% (P = .493), respectively. CONCLUSION: Based on Milan criteria as the benchmark for selecting HCC candidates to LT, both short- and long-term transplant survival rates achieved similar results when compared with patients without HCC. These results sustain transplantation as the treatment of choice for patients with cirrhosis and in the early stage of HCC.

Metalloproteinases 1 and 3 as Potential Biomarkers in Breast Cancer Development.

Breast cancer continues to be one of the main causes of morbidity and mortality globally and was the leading cause of cancer death in women in Spain in 2020. Early diagnosis is one of the most effective methods to lower the incidence and mortality rates of breast cancer. The human metalloproteinases (MMP) mainly function as proteolytic enzymes degrading the extracellular matrix and plays important roles in most steps of breast tumorigenesis. This retrospective cohort study shows the immunohistochemical expression levels of MMP-1, MMP-2, MMP-3, and MMP-9 in 154 women with breast cancer and 42 women without tumor disease. The samples of breast tissue are assessed using several tissue matrices (TMA). The percentages of staining (≤50%->50%) and intensity levels of staining (weak, moderate, or intense) are considered. The immunohistochemical expression of the MMP-1-intensity (p = 0.043) and MMP-3 percentage (p = 0.018) and intensity, (p = 0.025) present statistically significant associations with the variable group (control-case); therefore, expression in the tumor tissue samples of these MMPs may be related to the development of breast cancer. The relationships between these MMPs and some clinicopathological factors in breast cancer are also evaluated but no correlation is found. These results suggest the use of MMP-1 and MMP-3 as potential biomarkers of breast cancer diagnosis.