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Endometriosis is a prevalent gynecological condition, affecting around 10% of reproductive-age women. Inflammatory processes associated with endometriosis may contribute to endothelial dysfunction. Increased skin accumulation of advanced glycation end-products (AGEs), reflecting arterial stiffness, potentially links endometriosis with elevated risk of cardiovascular events. We hypothesized that patients with endometriosis have impaired endothelial function as well as increased arterial stiffness and AGE skin accumulation, compared to healthy controls. We compared endothelial function, arterial stiffness, and levels of AGEs in patients suffering from endometriosis and in healthy controls. The study included 45 women aged 20 to 40: 21 patients with endometriosis and 24 healthy controls, matched in terms of age, BMI, and blood pressure values. Endo-PAT 2000 device was used for non-invasive assessment of (i) endothelial function, expressed as Reactive Hyperemia Index (RHI), and (ii) arterial stiffness, expressed as Augmentation Index (AI) and Augmentation Index at 75 heart beats/min (AI@75). Endothelial dysfunction was defined as an RHI value ≤ 1.67. AGE Reader device was used for non-invasive evaluation of skin AGE level accumulation. Patients with endometriosis had lower mean RHI values (1.69 ± 0.54 vs. 2.02 ± 0.48, p = 0.037) and a higher prevalence of endothelial dysfunction, (52.4% vs. 20.8%, p = 0.027) compared to healthy controls. Skin AGE level was higher in patients with endometriosis, compared to controls (2.00 ± 0.57 vs. 1.70 ± 0.24, p = 0.013). There were no significant differences in AI and AI@75 between the two groups. Patients with endometriosis have impaired endothelial function and higher AGE skin accumulation, which are well-established preclinical manifestations of increased cardiovascular risk. There is a great need for comprehensive cardiovascular risk assessments in women with endometriosis to prevent the development of potential atherosclerotic-based complications.
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Enfermedades Cardiovasculares , Endometriosis , Endotelio Vascular , Productos Finales de Glicación Avanzada , Rigidez Vascular , Humanos , Femenino , Endometriosis/fisiopatología , Endometriosis/complicaciones , Adulto , Endotelio Vascular/fisiopatología , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/fisiopatología , Productos Finales de Glicación Avanzada/metabolismo , Factores de Riesgo de Enfermedad Cardiaca , Adulto Joven , Estudios de Casos y Controles , Piel , Factores de RiesgoRESUMEN
Background/Objectives: Data regarding the outcomes of liver transplantation in disabled, highly dependent, and legally incapacitated adults are scarce, likely due to the infrequency of these procedures in such populations. Multicenter studies in adult transplant centers have shown that patients with coexisting intellectual and developmental disabilities (IDDs) may be denied transplantation because of their expected low longevity and the complexities associated with managing post-transplant care. We examined the long-term patient and graft outcomes in highly dependent, incapacitated patients with IDDs who underwent elective transplantation for chronic liver disease. Methods: Six adult patients who underwent liver transplantation for primary biliary cholangitis (n = 2), hepatitis C cirrhosis (n = 2), Wilson's disease (n = 1), and autoimmune hepatitis (n = 1) were included. The main causes of their disability were infantile cerebral palsy, myotonia, and Niemann-Pick disease. Results: Four of the six patients were women, with a median age of 26 (range: 23-36) years. Only one patient died during follow-up. Their 1- and 5-year survival rates were 100 and 75%, respectively, which were not statistically different from those of the general cohort of electively transplanted patients (95.8 and 90.1%, respectively) (p = 0.35). Conclusions: Adult patients who are highly dependent, disabled, or legally incapable should not be denied liver transplantation because of poor long-term survival rates. Physiological disorders and psychiatric comorbidities should not prevent patients from receiving life-saving surgeries due to poor postoperative compliance or low quality of life.
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Risk stratification in heart failure with mildly-reduced ejection fraction (HFmrEF) remains challenging. We evaluated the predictive value of advanced glycation end products (AGEs) and plasma concentrations of extracellular vesicles (EVs) for the systolic and diastolic dysfunction progression in HFmrEF patients. Skin AGE accumulation was measured using AGE Reader. Plasma EV concentrations were measured using flow cytometry. Among 74 patients enrolled, 13 (18%) had systolic dysfunction progression and 5 (7%) had diastolic dysfunction progression during 6.5 months follow-up. Leukocyte EVs concentrations were higher in patients with systolic dysfunction progression (p = 0.002) and predicted the progression with 75.0% sensitivity and 58.3% specificity, independent of other clinical variables (OR 4.72, 95% CI 0.99-22.31). Skin AGE levels and concentrations of other EV subtypes were not associated with systolic or diastolic dysfunction progression. Increased leukocyte EVs concentrations are associated with 4.7-fold higher odds of systolic dysfunction progression in HFmrEF patients.
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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.
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Hepatectomía , Fallo Hepático , Trasplante de Hígado , Complicaciones Posoperatorias , Humanos , Trasplante de Hígado/métodos , Trasplante de Hígado/efectos adversos , Adulto , Persona de Mediana Edad , Masculino , Estudios Retrospectivos , Femenino , Hepatectomía/métodos , Hepatectomía/efectos adversos , Anciano , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Fallo Hepático/etiología , Fallo Hepático/cirugía , Adulto Joven , Resultado del TratamientoRESUMEN
Introduction: Laparoscopic liver resection is a challenging surgical procedure that may require prolonged operation time, particularly during the learning curve. Operation time significantly decreases with increasing experience; however, prolonged operation time may significantly increase the risk of postoperative complications. Aim: To assess whether prolonged operation time over the benchmark value influences short-term postoperative outcomes after laparoscopic liver resection. Material and methods: A retrospective cohort study based on data from the National Polish Registry of Minimally Invasive Liver Surgery was performed. A total of 197 cases consisting of left lateral sectionectomy (LLS), left hemihepatectomy (LH), and right hemihepatectomy (RH) with established benchmark values for operation time were included. Data about potential confounders for prolonged operation time and worse short-term outcomes were exported. Results: Most cases (129; 65.5%) were performed during the learning curve, while the largest rate was observed in LLS (57; 78.1%). Median operation time exceeded the benchmark value in LLS (Me = 210 min) and LH (Me = 350 min), while in RH the benchmark value was exceeded in 39 (44.3%) cases. Textbook outcomes were achieved in 138 (70.1%) cases. Univariate analysis (OR = 1.11; 95% CI: 0.61-2.06; p = 0.720) and multivariate analysis (OR = 1.16; 95% CI: 0.50-2.68; p = 0.734) did not reveal a significant impact of prolonged surgery on failing to achieve a textbook outcome. Conclusions: Prolonging the time of laparoscopic liver resection does not significantly impair postoperative results. There is no reason related to the patients' safety to avoid prolonging the time of laparoscopic liver resection over the benchmark value.
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Metabolic dysfunction-associated fatty liver disease (MAFLD) is a hepatic manifestation of the metabolic syndrome. It is one of the most common liver diseases worldwide and shows increasing prevalence rates in most countries. MAFLD is a progressive disease with the most severe cases presenting as advanced fibrosis or cirrhosis with an increased risk of hepatocellular carcinoma. Gut microbiota play a significant role in the pathogenesis and progression of MAFLD by disrupting the gut-liver axis. The mechanisms involved in maintaining gut-liver axis homeostasis are complex. One critical aspect involves preserving an appropriate intestinal barrier permeability and levels of intestinal lumen metabolites to ensure gut-liver axis functionality. An increase in intestinal barrier permeability induces metabolic endotoxemia that leads to steatohepatitis. Moreover, alterations in the absorption of various metabolites can affect liver metabolism and induce liver steatosis and fibrosis. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a class of drugs developed for the treatment of type 2 diabetes mellitus. They are also commonly used to combat obesity and have been proven to be effective in reversing hepatic steatosis. The mechanisms reported to be involved in this effect include an improved regulation of glycemia, reduced lipid synthesis, ß-oxidation of free fatty acids, and induction of autophagy in hepatic cells. Recently, multiple peptide receptor agonists have been introduced and are expected to increase the effectiveness of the treatment. A modulation of gut microbiota has also been observed with the use of these drugs that may contribute to the amelioration of MAFLD. This review presents the current understanding of the role of the gut-liver axis in the development of MAFLD and use of members of the GLP-1 RA family as pleiotropic agents in the treatment of MAFLD.
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Microbioma Gastrointestinal , Receptor del Péptido 1 Similar al Glucagón , Hígado , Humanos , Receptor del Péptido 1 Similar al Glucagón/agonistas , Receptor del Péptido 1 Similar al Glucagón/metabolismo , Microbioma Gastrointestinal/efectos de los fármacos , Hígado/metabolismo , Hígado/efectos de los fármacos , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/microbiología , Animales , Síndrome Metabólico/tratamiento farmacológico , Síndrome Metabólico/metabolismo , Síndrome Metabólico/microbiología , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/farmacología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/microbiología , Incretinas/uso terapéutico , Incretinas/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/microbiología , Agonistas Receptor de Péptidos Similares al GlucagónRESUMEN
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. The aim of this study was 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 static cold storage arm (78 patients) and dHOPE arm (26 patients). Endpoints of interest were occurrence of biliary complications (biliary fistula, anastomotic, and nonanastomotic strictures) and overall patient (OS) and graft survival (GS) during two-year follow-up. RESULTS: A total of 36 patients developed biliary complications (at least one event) - 6 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 non-anastomotic 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 result in the study population - OS: 92.3% in dHOPE and 83.9% in SCS (P=0.35), and GS: 92.3% and 81.4% (P=0.23), respectively. However, 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 benefits of dHOPE in low-risk grafts.
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Orthotopic liver transplantation stands as the sole curative solution for end-stage liver disease. Nevertheless, the discrepancy between the demand and supply of grafts in transplant medicine greatly limits the success of this treatment. The increasing global shortage of organs necessitates the utilization of extended criteria donors (ECD) for liver transplantation, thereby increasing the risk of primary graft dysfunction (PGD). Primary graft dysfunction (PGD) encompasses early allograft dysfunction (EAD) and the more severe primary nonfunction (PNF), both of which stem from ischemia-reperfusion injury (IRI) and mitochondrial damage. Currently, the only effective treatment for PNF is secondary transplantation within the initial post-transplant week, and the occurrence of EAD suggests an elevated, albeit still uncertain, likelihood of retransplantation urgency. Nonetheless, the ongoing exploration of novel IRI mitigation strategies offers hope for future improvements in PGD outcomes. Establishing an intuitive and reliable tool to predict upcoming graft dysfunction is vital for early identification of high-risk patients and for making informed retransplantation decisions. Accurate diagnostics for PNF and EAD constitute essential initial steps in implementing future mitigation strategies. Recently, novel methods for PNF prediction have been developed, and several models for EAD assessments have been introduced. Here, we provide an overview of the currently scrutinized predictive tools for PNF and EAD evaluation strategies, accompanied by recommendations for future studies.
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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.
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Bilis , Colangitis Esclerosante , Cálculos Biliares , Humanos , Colangitis Esclerosante/metabolismo , Colangitis Esclerosante/patología , Cálculos Biliares/metabolismo , Cálculos Biliares/química , Cálculos Biliares/patología , Bilis/química , Bilis/metabolismo , Masculino , Femenino , Persona de Mediana Edad , Adulto , Anciano , Adulto Joven , Proteínas Ligadas a GPIRESUMEN
Transarterial chemoembolization (TACE) represent the standard of therapy for non-operative hepatocellular carcinoma (HCC), while prediction of long term treatment outcomes is a complex and multifactorial task. In this study, we present a novel machine learning approach utilizing radiomics features from multiple organ volumes of interest (VOIs) to predict TACE outcomes for 252 HCC patients. Unlike conventional radiomics models requiring laborious manual segmentation limited to tumoral regions, our approach captures information comprehensively across various VOIs using a fully automated, pretrained deep learning model applied to pre-TACE CT images. Evaluation of radiomics random survival forest models against clinical ones using Cox proportional hazard demonstrated comparable performance in predicting overall survival. However, radiomics outperformed clinical models in predicting progression-free survival. Explainable analysis highlighted the significance of non-tumoral VOI features, with their cumulative importance superior to features from the largest liver tumor. The proposed approach overcomes the limitations of manual VOI segmentation, requires no radiologist input and highlight the clinical relevance of features beyond tumor regions. Our findings suggest the potential of this radiomics models in predicting TACE outcomes, with possible implications for other clinical scenarios.
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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Aprendizaje Profundo , Neoplasias Hepáticas , Tomografía Computarizada por Rayos X , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patología , Quimioembolización Terapéutica/métodos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Tomografía Computarizada por Rayos X/métodos , Resultado del Tratamiento , RadiómicaRESUMEN
BACKGROUND: There is continuous growth of combined liver-kidney transplantation (CLKTx) numbers with remarkable outcomes, especially among patient with liver cirrhosis and end-stage renal disease. The aim was to present a single center experience. METHODS: Twenty patients (9 males) with a mean age of 48 (range: 20-62) years underwent CLKTx from 2005 to 2022. Indications were polycystic liver and kidney diseases (ADPKD) in 12 cases, cirrhosis due to hepatitis (4 patients), and 1 case of amyloidosis, alcoholic liver disease, nonalcoholic steatosis, and congenital hepatic fibrosis with concomitant glomerulonephritis. After hepatectomy, half of the patients had orthotopic liver transplantation with piggy-back technique, and the other had conventional technique. All but 1 recipient had biliary end-to-end anastomosis. 3 patients had preemptive kidney graft transplantation. 4 underwent simultaneous right-side nephrectomy due to volume of the right kidney. Kidney was transplanted from the separate incision after abdominal closure with typical anastomoses. Tacrolimus, mycophenolate mofetile, basiliximab, and steroids were applied for all recipients. RESULTS: Mean follow-up was 57.7 ± 54 months. No primary non-function of the grafts occurred. Delayed kidney graft function (DGF) occurred in 8 patients. Three-month, 1-year, and 5-year cumulative survival rates were: 90%, 80%, and 72% respectively. None of the patients required retransplantation, and 1 recipient returned to hemodialysis 19 months after transplantation. Preemptive kidney transplantation and simultaneous right-side nephrectomy were not significant for DGF and recipient survival. No deaths within the first year occurred in piggy-back technique. CONCLUSIONS: CLKTx is safe and effective in the treatment of both liver and kidney failure.
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Trasplante de Riñón , Trasplante de Hígado , Humanos , Masculino , Adulto , Femenino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto Joven , Fallo Renal Crónico/cirugía , Estudios Retrospectivos , Supervivencia de InjertoRESUMEN
BACKGROUND: The uterine artery pulsatility index (UtA PI) is associated with blood flow to the placenta. Its increased values imply impaired placentation. This study aimed to evaluate UtA PI measurements in first-trimester ultrasound in pregnancies after kidney (KTx) or liver transplantation (LTx) and its relationship with perinatal outcome. MATERIALS AND METHODS: A retrospective analysis of 72 pregnancies in female kidney (35) or liver (37) transplant recipients between 2017 and 2023 was performed. Data concerning UtA PI were available for 17 kidney and 19 liver recipients. Statistical analysis of variables between KTx and LTx groups and the correlation with perinatal outcomes was performed using Student's t test and Pearson's correlation with P < .05 considered statistically significant. RESULTS: The mean UtA PI results were similar, and there were no statistical differences between the group of pregnant kidney and liver recipients with mean values of 1.46 (SD 0.44] and 1.73 (SD 0.51] respectively (P = .10). The mean neonate birth weight was lower in KTx group (2158 g ([SD 723 g]) compared with the LTx group (2780 g [SD 754g]; P =.02). In the KTx and LTx groups, mean UtA PI was in negative correlation with Apgar score in the first minute (P = .04, P = .01 respectively). CONCLUSIONS: Uterine artery Doppler is useful in predicting perinatal outcomes in the general population and organ recipient pregnancies, even in the early stages of pregnancy, as we observed the correlation between UtA PI and Apgar score. Pregnant kidney recipients remain at higher risk for complications and more unpredictable outcomes than liver recipients.
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Trasplante de Riñón , Trasplante de Hígado , Resultado del Embarazo , Flujo Pulsátil , Arteria Uterina , Humanos , Embarazo , Femenino , Arteria Uterina/diagnóstico por imagen , Estudios Retrospectivos , Adulto , Ultrasonografía Prenatal , Recién NacidoRESUMEN
Despite decades of research, the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD) is still not completely understood. Based on the evidence from preclinical models, one of the factors proposed as a main driver of disease development is oxidative stress. This study aimed to search for the resemblance between the profiles of oxidative stress and antioxidant defense in the animal model of MASLD and the group of MASLD patients. C57BL/6J mice were fed with the Western diet for up to 24 weeks and served as the animal model of MASLD. The antioxidant profile of mice hepatic tissue was determined by liquid chromatography-MS3 spectrometry (LC-MS/MS). The human cohort consisted of 20 patients, who underwent bariatric surgery, and 6 controls. Based on histological analysis, 4 bariatric patients did not have liver steatosis and as such were also classified as controls. Total antioxidant activity was measured in sera and liver biopsy samples. The hepatic levels of antioxidant enzymes and oxidative damage were determined by Western Blot. The levels of antioxidant enzymes were significantly altered in the hepatic tissue of mice with MASLD. In contrast, there were no significant changes in the antioxidant profile of hepatic tissue of MASLD patients, except for the decreased level of carbonylated proteins. Decreased protein carbonylation together with significant correlations between the thioredoxin system and parameters describing metabolic health suggest alterations in the thiol-redox signaling. Altogether, these data show that even though the phenotype of mice closely resembles human MASLD, the animal-to-human translation of cellular and molecular processes such as oxidative stress may be more challenging.
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Hígado Graso , Enfermedades Metabólicas , Humanos , Animales , Ratones , Ratones Endogámicos C57BL , Antioxidantes , Cromatografía Liquida , Espectrometría de Masas en Tándem , Estrés Oxidativo , Modelos AnimalesRESUMEN
BACKGROUND: The need for safe and efficient dissemination of minimally invasive approach in liver surgery is among the current challenges for hepatobiliary surgeons. After the stage of innovators and pioneers, the following countries should adopt a laparoscopic approach. The aim of this study was to assess the national experience and trend in implementing laparoscopic liver resection (LLR) in Poland. MATERIALS AND METHODS: A national registry of LLR performed in Poland was established in June 2020. All LLR cases performed before were included retrospectively, followed by prospectively collected new cases. Baseline characteristics, preoperative and intraoperative data, short-term results and long-term follow-up were recorded. RESULTS: Since 2010 up to the end of 2022 there were 718 LLRs performed in Poland. The national rate of laparoscopic approach has gradually increased since 2017 ( P <0.001), reaching the rate of 11.7% in 2022. There were 443 (61.7%), 107 (14.9%), and 168 (23.4%) LLRs performed in accordance to increasing grades of difficulty. The move towards more demanding cases had an increasing trend over the years ( P <0.001). Total intraoperative adverse event and postoperative severe complications rates were estimated for 13.5% ( n =97) and 6.7% ( n =48), respectively. 30-day reoperation, readmission and postoperative mortality rates were 3.6% ( n =26), 2.8% ( n =20), and 0.8% ( n =6), respectively. While the R0 resection margin was assessed in 643 (89.6%) cases, the total textbook outcomes (TO) were achieved in 525 (74.5%) cases. Overcoming the learning curve of 60 LLRs, resulted in an increasing TO rate from 72.3 to 80.6% ( P =0.024). CONCLUSIONS: It is the first national analysis of a laparoscopic approach in liver surgery in Poland. An increasing trend of minimizing invasiveness in liver resection has been observed. Responsible selection of cases in accordance with difficulty may provide results within global benchmark values and textbook outcomes already during the learning curve.
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Laparoscopía , Neoplasias Hepáticas , Humanos , Estudios Retrospectivos , Neoplasias Hepáticas/cirugía , Polonia , Hepatectomía/efectos adversos , Hepatectomía/métodos , Laparoscopía/efectos adversos , Laparoscopía/métodos , Complicaciones Posoperatorias/etiología , Tiempo de InternaciónRESUMEN
BACKGROUND & AIMS: There is controversy regarding the optimal calcineurin inhibitor type after liver transplant(ation) (LT) for primary sclerosing cholangitis (PSC). We compared tacrolimus with cyclosporine in a propensity score-matched intention-to-treat analysis based on registries representing nearly all LTs in Europe and the US. METHODS: From the European Liver Transplant Registry (ELTR) and Scientific Registry of Transplant Recipients (SRTR), we included adult patients with PSC undergoing a primary LT between 2000-2020. Patients initially treated with cyclosporine were propensity score-matched 1:3 with those initially treated with tacrolimus. The primary outcomes were patient and graft survival rates. RESULTS: The propensity score-matched sample comprised 399 cyclosporine-treated and 1,197 tacrolimus-treated patients with PSC. During a median follow-up of 7.4 years (IQR 2.3-12.8, 12,579.2 person-years), there were 480 deaths and 231 re-LTs. The initial tacrolimus treatment was superior to cyclosporine in terms of patient and graft survival, with 10-year patient survival estimates of 72.8% for tacrolimus and 65.2% for cyclosporine (p <0.001) and 10-year graft survival estimates of 62.4% and 53.8% (p <0.001), respectively. These findings were consistent in the subgroups according to age, sex, registry (ELTR vs. SRTR), time period of LT, MELD score, and diabetes status. The acute rejection rates were similar between groups. In the multivariable Cox regression analysis, tacrolimus (hazard ratio 0.72, p <0.001) and mycophenolate use (hazard ratio 0.82, p = 0.03) were associated with a reduced risk of graft loss or death, whereas steroid use was not significant. CONCLUSIONS: Tacrolimus is associated with better patient and graft survival rates than cyclosporine and should be the standard calcineurin inhibitor used after LT for patients with PSC. IMPACT AND IMPLICATIONS: The optimal calcineurin inhibitor to use after liver transplantation in patients with primary sclerosing cholangitis has yet to be firmly established. Since randomized trials with long follow-up are unlikely to be performed, multicontinental long-term registry data are essential in informing clinical practices. Our study supports the practice of using tacrolimus instead of cyclosporine in the initial immunosuppressive regimen after liver transplantation for patients with primary sclerosing cholangitis. The retrospective registry-based design is a limitation.
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Colangitis Esclerosante , Trasplante de Hígado , Adulto , Humanos , Tacrolimus/uso terapéutico , Ciclosporina/uso terapéutico , Inhibidores de la Calcineurina , Estudios Retrospectivos , Trasplante de Hígado/efectos adversos , Colangitis Esclerosante/tratamiento farmacológico , Colangitis Esclerosante/cirugía , Colangitis Esclerosante/etiología , Análisis de Intención de Tratar , Puntaje de Propensión , Inmunosupresores/uso terapéutico , Rechazo de Injerto/epidemiología , Rechazo de Injerto/prevención & control , Rechazo de Injerto/tratamiento farmacológico , Supervivencia de InjertoRESUMEN
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.
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Neoplasias Hepáticas , Trasplante de Hígado , Tumores Neuroendocrinos , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Tumores Neuroendocrinos/cirugía , Tumores Neuroendocrinos/patología , Antígeno Ki-67 , Neoplasias Hepáticas/patología , Recurrencia Local de NeoplasiaRESUMEN
Introduction: Over the past three decades, almost every type of abdominal surgery has been performed and refined using the laparoscopic technique. Surgeons are applying it for more procedures, which not so long ago were performed only in the classical way. The position of laparoscopic surgery is therefore well established, and in many operations it is currently the recommended and dominant method. Aim: The aim of the preparation of these guidelines was to concisely summarize the current knowledge on laparoscopy in acute abdominal diseases for the purposes of the continuous training of surgeons and to create a reference for opinions. Material and methods: The development of these recommendations is based on a review of the available literature from the PubMed, Medline, EMBASE and Cochrane Library databases from 1985 to 2022, with particular emphasis on systematic reviews and clinical recommendations of recognized scientific societies. Recommendations were formulated in a directive form and evaluated by a group of experts using the Delphi method. Results and conclusions: There are 63 recommendations divided into 12 sections: diagnostic laparoscopy, perforated ulcer, acute pancreatitis, incarcerated hernia, acute cholecystitis, acute appendicitis, acute mesenteric ischemia, abdominal trauma, bowel obstruction, diverticulitis, laparoscopy in pregnancy, and postoperative complications requiring emergency surgery. Each recommendation was supported by scientific evidence and supplemented with expert comments. The guidelines were created on the initiative of the Videosurgery Chapter of the Association of Polish Surgeons and are recommended by the national consultant in the field of general surgery. The first part of the guidelines covers 5 sections and the following challenges for surgical practice: diagnostic laparoscopy, perforated ulcer, acute pancreatitis, incarcerated hernia and acute cholecystitis. Contraindications for laparoscopy and the ERAS program are discussed.
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Transarterial chemoembolization (TACE) is used as a bridging treatment in liver transplant candidates with hepatocellular carcinoma (HCC). Alpha-fetoprotein (AFP) is the main tumor marker used for HCC surveillance. The aim of this study was to assess the potential of using the AFP change after the first TACE in the prediction of complete tumor necrosis. The study comprised 101 patients with HCC who underwent liver transplantation (LT) after TACE in the period between January 2011 and December 2020. The ΔAFP was defined as the difference between the AFP value before the first TACE and AFP either before the second TACE or the LT. The receiver operator characteristics (ROC) curves were used to identify an optimal cut-off value. Complete tumor necrosis was found in 26.1% (18 of 69) and 6.3% (2 of 32) of patients with an initial AFP level under and over 100 ng/mL, respectively (p = 0.020). The optimal cut-off value of ΔAFP for the prediction of complete necrosis was a decline of ≥10.2 ng/mL and ≥340.5 ng/mL in the corresponding subgroups. Complete tumor necrosis rates were: 62.5% (5 of 8) in patients with an initial AFP < 100 ng/mL and decline of ≥10.2 ng/mL; 21.3% (13 of 61) in patients with an initial AFP < 100 ng/mL and decline of <10.2 ng/mL; 16.7% (2 of 12) in patients with an initial AFP > 100 ng/mL and decline of ≥340.5 ng/mL; and null in 20 patients with an initial AFP > 100 ng/mL and decline of <340.5 ng/mL, respectively (p = 0.003). The simple scoring system, based on the initial AFP and AFP decline after the first treatment, distinguished between a high, intermediate and low probability of complete necrosis, with an area under the ROC curve of 0.699 (95% confidence intervals 0.577 to 0.821, p = 0.001). Combining the initial AFP with its change after the first treatment enables early identification of the efficacy of TACE.
RESUMEN
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.