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BACKGROUND: Wailitst lost is an critical issue and we investigated the long-term effect of insufficient liver functional reserve at liver transplantation evaluation on waitlist outcomes in patients with hepatocellular carcinoma (HCC). METHODS: Clinical data of patients with HCC waitlisted for liver transplantation were retrospectively collected from a single hospital cohort during the period from 2014 to 2021. Parameters of liver reserve, including cirrhosis, Child-Pugh grade, and Model for End-Stage Liver Disease (MELD) scores, were analyzed for patient survival, after adjustment for tumor factors. RESULTS: Of 292 eligible patients, 94.2% had cirrhosis, 55.8% had Child-Pugh grade B or C, and the median MELD score was 13.2. The median follow-up time was 2.2 years, with a dropout rate of 62.7%. Eighty-nine candidates (30.5%) eventually received liver transplant, including 67 from live donors. The estimated 1-year mortality rate reached 40.6% in 203 patients who remained on the waitlist without receiving a transplant, of whom 143 died. Most deaths were attributed to liver failure (37.1%) and cancer death (35.7%). After we adjusted for tumor confounders, including alpha fetoprotein, primary HCC stage, tumor number at evaluation, and sequential cancer treatment before and while waiting, hazard ratios (HRs) for patient survival were 1.69 (95% confidence interval, 1.18-2.41) for cirrhotic stage B or C, 1.07 (1.04-1.10) for MELD scores, and 1.14 (1.04-1.25) for tumor size at transplant evaluation. Transplantation was a protective disease modifier with adjusted HR 0.22 (0.14-0.33). CONCLUSION: Insufficient liver functional reserve poses more risk than expected to liver transplant waitlist outcomes with HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Trasplante de Hígado , Listas de Espera , Humanos , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Femenino , Listas de Espera/mortalidad , Persona de Mediana Edad , Estudios Retrospectivos , Estudios Longitudinales , Anciano , Adulto , Tasa de SupervivenciaRESUMEN
BACKGROUND: Preoperative imaging evaluation of liver volume and hepatic steatosis for the donor affects transplantation outcomes. However, computed tomography (CT) for liver volumetry and magnetic resonance spectroscopy (MRS) for hepatic steatosis are time consuming. Therefore, we investigated the correlation of automated 3D-multi-echo-Dixon sequence magnetic resonance imaging (ME-Dixon MRI) and its derived proton density fat fraction (MRI-PDFF) with CT liver volumetry and MRS hepatic steatosis measurements in living liver donors. METHODS: This retrospective cross-sectional study was conducted from December 2017 to November 2022. We enrolled donors who received a dynamic CT scan and an MRI exam within 2 days. First, the CT volumetry was processed semiautomatically using commercial software, and ME-Dixon MRI volumetry was automatically measured using an embedded sequence. Next, the signal intensity of MRI-PDFF volumetric data was correlated with MRS as the gold standard. RESULTS: We included the 165 living donors. The total liver volume of ME-Dixon MRI was significantly correlated with CT (r = 0.913, p < 0.001). The fat percentage measured using MRI-PDFF revealed a strong correlation between automatic segmental volume and MRS (r = 0.705, p < 0.001). Furthermore, the hepatic steatosis group (MRS ≥5%) had a strong correlation than the non-hepatic steatosis group (MRS <5%) in both volumetric (r = 0.906 vs. r = 0.887) and fat fraction analysis (r = 0.779 vs. r = 0.338). CONCLUSION: Automated ME-Dixon MRI liver volumetry and MRI-PDFF were strongly correlated with CT liver volumetry and MRS hepatic steatosis measurements, especially in donors with hepatic steatosis.
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BACKGROUND AND AIM: This study aimed to investigate the survival outcomes of antiviral agents (direct-acting antivirals [DAAs] or interferon [IFN]) in patients with hepatitis C virus who underwent liver resection for primary hepatocellular carcinoma. METHODS: This retrospective single-center study included 247 patients, between 2013 and 2020, being treated with DAAs (n = 93), IFN (n = 73), or no treatment (n = 81). Overall survival (OS), recurrence-free survival (RFS), and risk factors were analyzed. RESULTS: After a median follow-up time of 50.4 months, the rates of 5-year OS and RFS in the IFN, DAA, and no treatment groups were 91.5% and 55.4%, 87.2% and 39.8%, and 60.9% and 26.7%, respectively. One hundred and twenty-eight (51.6%) patients developed recurrence; recurrence was mostly (86.7%) intrahepatic, and 58 (23.4%) developed early recurrence, most of which received no antiviral treatment. The OS and RFS were similar between patients who received antiviral treatment before (50.0%) and after surgery, but longer survival was observed in patients achieving sustained virologic response. In multivariate analysis, antiviral treatment was protective for OS (hazard ratio [HR] 0.475, 95% confidence interval [CI]: 0.242-0.933) with significance but not RFS, in contrast to microvascular invasion (OS HR 3.389, 95% CI: 1.637-7.017; RFS HR 2.594, 95% CI: 1.520-4.008). In competing risk analysis, DAAs (subdistribution HR 0.086, 95% CI: 0.007-0.991) were protective against hepatic decompensation events but not recurrence events. CONCLUSION: In patients with hepatitis C virus, antiviral treatment suggested OS benefit for primary hepatocellular carcinoma after resection, and DAAs might be protective against hepatic decompensation. Following adjustment for oncological factors, IFN and DAA treatment was not significantly advantageous relative to the other.
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Carcinoma Hepatocelular , Hepatitis C Crónica , Hepatitis C , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Antivirales/uso terapéutico , Neoplasias Hepáticas/patología , Estudios Retrospectivos , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/cirugía , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Hepacivirus , Respuesta Virológica Sostenida , Recurrencia Local de Neoplasia/complicacionesRESUMEN
BACKGROUND: Sarcopenia is a common finding in patients with decompensated cirrhosis without effective therapy. We aimed to examine whether a transjugular portosystemic shunt (TIPS) could improve the abdominal muscle mass assessed by cross-sectional images in patients with decompensated cirrhosis and to investigate the association of imaging-defined sarcopenia with the prognosis of such patients. METHODS: In this retrospective observational study, we enrolled 25 Decompensated cirrhosis patients aged >20 who received TIPS for the control of variceal bleeding or refractory ascites between April 2008 and April 2021. All of them underwent preoperative computed tomography or magnetic resonance imaging, which was used to determine psoas muscle (PM) and paraspinal muscle (PS) indices at the third lumbar vertebra. First, we compared baseline muscle mass with muscle mass at 6 and 12 months after TIPS placement and analyzed PM- and PS-defined sarcopenia to predict mortality. RESULTS: Among 25 patients, 20 (80.0%) and 12 (48.0%) had PM- and PS-defined sarcopenia, respectively, at baseline. In total, 16 and 8 patients were followed up for 6 and 12 months, respectively. All imaging-based muscle measurements performed 12 months after TIPS placement were significantly greater than the baseline measurements (all p < 0.05). Unlike patients with PS-defined sarcopenia (p = 0.529), patients with PM-defined sarcopenia had poorer survival than did patients without (p = 0.036). CONCLUSION: PM mass in patients with decompensated cirrhosis may increase by 6 or 12 months after TIPS placement and imply a better prognosis. Patients with preoperative PM-defined sarcopenia may suggest poorer survival.
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Várices Esofágicas y Gástricas , Derivación Portosistémica Intrahepática Transyugular , Sarcopenia , Humanos , Derivación Portosistémica Intrahepática Transyugular/métodos , Factores de Riesgo , Cirrosis Hepática/complicaciones , Cirrosis Hepática/cirugía , Sarcopenia/complicaciones , Sarcopenia/diagnóstico por imagen , Hemorragia Gastrointestinal , Músculos Abdominales/diagnóstico por imagen , Músculos Abdominales/cirugía , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: To investigate the changes in transplantability between primary and recurrent Hepatocellular carcinoma (HCC) after hepatic resection (HR) and the risk factors for nontransplantable recurrence (NTR). METHODS: Consecutive 3122 patients who received HR for primary HCC between 2001 and 2019 were analyzed for changes in transplantability. Predictors of survival and NTR were evaluated using a competing risk analysis. RESULTS: After a median follow-up of 78.3 months, the 5-year overall survival rate was 82.6%. Also, 58.2% of them developed recurrence after a median of 45.6 months. Recurrence occurred in 1205 and 611 patients with primary transplantable and nontransplantable HCC, respectively, of whom 26.1% and 63.2%, respectively, had NTR. Tumor diameter >3 cm [subdistribution hazard ratios (95% CI), 2.00 (1.62-2.48)], major resection [1.20 (1.00-1.43)], pathological grade >2 [1.28 (1.07-1.52)], microvascular invasion [1.74 (1.45-2.08)], and early recurrence (<1 year) [9.22 (7.83-10.87)] were associated with NTR. The overall transplantable pool increased from 72.3% to 77.5%. CONCLUSION: Microvascular invasion and early recurrence were risk factors for NTR. Nonetheless, the transplantable pool increased after HR, 41.8% of the patients had no recurrence and may not require liver transplantation. If the patient's liver function is acceptable, HR should be considered the treatment of choice for HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Trasplante de Hígado , Humanos , Carcinoma Hepatocelular/cirugía , Neoplasias Hepáticas/cirugía , Hepatectomía , Factores de Riesgo , Trasplante de Hígado/efectos adversos , Recurrencia Local de Neoplasia/patología , Estudios RetrospectivosRESUMEN
BACKGROUND: Lung transplantation is a therapeutic option for patients with end-stage lung disease. However, the increase in organ demand has surpassed the number of donors, with many patients unable to outlive the long waiting period. This study aimed to assess mortality and its risk factors in patients on the waiting list for lung transplantation in a single medical centre. METHODS: All evaluated clinical and laboratory data of the patients with end-stage lung disease assessed for lung transplantation between February 2005 and November 2018 in National Taiwan University Hospital were recorded in the waiting list database. The patients in this study were divided into two groups: survival and death groups. RESULTS: Between February 2005 and November 2018, 169 patients were enrolled in the waiting list. Thirty-one patients were alive and waiting for the chance of lung transplantation, 56 underwent lung transplantation, and 82 died while waiting. The mean age of all patients was 43.7 years, and 91 were women. The mean body mass index (BMI) was 20.3. The most common blood type was type O. All patients were in New York Heart Association (NYHA) class III or IV. After analysis of the two groups, lower BMI presented as a mortality factor. CONCLUSION: This is the first Taiwanese study to describe the mortality factors in patients waiting for lung transplantation. The main factors influencing the survival of these patients were lower BMI, NYHA class IV, and diseases which cause end-stage lung diseases (infection and pulmonary fibrosis).
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Trasplante de Pulmón , Fibrosis Pulmonar , Humanos , Femenino , Adulto , Masculino , Listas de Espera , Donantes de Tejidos , Factores de RiesgoRESUMEN
BACKGROUND: Amiodarone is an antiarrhythmic drug that has been recognized to induce hepatotoxicity. We report a case of acute-on-chronic liver failure (ACLF) in a patient who was receiving amiodarone for more than 2 years. The patient developed cirrhosis and suppurative microabscesses of the liver and died of progressive liver failure. CASE PRESENTATION: A 69-year-old woman with risk factors for nonalcoholic fatty liver disease (NAFLD) was treated with oral amiodarone at a daily dose of 400 mg for more than 2 years, until she developed epigastralgia and vomiting. Initial laboratory findings included leukocytosis and elevated liver enzymes. Images of abdominal computed tomography scan revealed diffusely increased hepatic attenuation density (in contrast to decreased density in NAFLD), hepatomegaly, periportal edema, and ascites. Liver biopsy targeting the hotspot identified through positron emission tomography confirmed the diagnosis of amiodarone-associated chronic steatohepatitis and superimposed microabscesses. The patient died of progressive ACLF despite intensive supportive care. CONCLUSION: Accumulation of amiodarone can result in chronic liver disease and pose an additional risk of ACLF following infection.
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Insuficiencia Hepática Crónica Agudizada , Amiodarona , Enfermedad Hepática Inducida por Sustancias y Drogas , Anciano , Amiodarona/efectos adversos , Antiarrítmicos/efectos adversos , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Femenino , Humanos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/tratamiento farmacológicoRESUMEN
BACKGROUND: Practical barriers exist in applying threshold-concept-based clinical teaching. We applied the practice model to the subject of acute liver failure and reported the experiences in teaching and learners' reactions. METHODS: The course comprised a 10-min online preclass video and a 1-h class with in-depth discussion. The video explained six extracted threshold concepts, which were labelled TC1-TC6. Three sets of feedback questionnaires were given to students. Questionnaires were provided after they watched the online video (Q1), after class (Q2), and before the end of the curriculum section (Q3). All the feedback questionnaires were analysed. RESULTS: Of the 136 attendees in the academic year 2018, 127 (93.4%), 69 (50.7%), and 112 (82.4%) completed the Q1, Q2, and Q3 questionnaires, respectively, and 48 (42.6%) provided comments. The degree of comprehension varied among threshold concepts and individual students. TC1 and TC2 were viewed as transformative for all three surveys. The threshold-concept-based learning process was satisfactory, and students could auto-reflect on the defining features of a threshold concept. Students became aware of their deficiencies in knowledge and acknowledged room for development with regard to their mindset for future patient management. CONCLUSION: Threshold-concept-based clinical teaching is a feasible strategy. Students' reflections indicate that thresholds were crossed, which does not guarantee that students' mindsets are ready for future clinical practice.
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Educación de Pregrado en Medicina , Educación Médica , Estudiantes de Medicina , Curriculum , Humanos , Estudiantes , Encuestas y CuestionariosRESUMEN
Surgical resection is the first-line curative treatment modality for resectable hepatocellular carcinoma (HCC). Anatomical resection (AR), described as systematic removal of a liver segment confined by tumor-bearing portal tributaries, may improve survival by reducing the risk of tumor recurrence compared with non-AR. In this article, we propose the rationale for AR and its universal adoption by providing supporting evidence from the advanced understanding of a tumor microenvironment and accumulating clinical experiences of locoregional tumor ablation therapeutics. AR may be advantageous because it completely removes the en-bloc by interrupting tumor vascular supply and thus extirpates the spreading of tumor microthrombi, if they ever exist, within the supplying portal vein. However, HCC is a hypervascular tumor that can promote neoangiogenesis in the local tumor microenvironment, which in itself can break through the anatomical boundary within the liver and even retrieve nourishment from extrahepatic vessels, such as inferior phrenic or omental arteries. Additionally, increasing clinical evidence for locoregional tumor ablation therapies, such as radiofrequency ablation, predominantly performed as a non-anatomical approach, suggests comparable outcomes for surgical resection, particularly in small HCC and colorectal, hepatic metastases. Moreover, liver transplantation for HCC, which can be considered as AR of the whole liver followed by implantation of a new graft, is not universally free from post-transplant tumor recurrence. Overall, AR should not be considered the gold standard among all surgical resection methods. Surgical resection is fundamentally reliant on choosing the optimal margin width to achieve en-bloc tumor niche removal while balancing between oncological radicality and the preservation of postoperative liver function. The importance of this is to liberate surgical resilience in hepatocellular carcinoma. The overall success of HCC treatment is determined by the clearance of the theoretical niche. Developing biomolecular-guided navigation device/technologies may provide surgical guidance toward the total removal of microscopic tumor niche to achieve superior oncological outcomes.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/cirugía , Hepatectomía , Humanos , Neoplasias Hepáticas/cirugía , Recurrencia Local de Neoplasia , Microambiente TumoralRESUMEN
BACKGROUND & AIMS: Intratumor heterogeneity has frequently been reported in patients with hepatocellular carcinoma (HCC). Thus, the reliability of single-region tumor samples for evaluation of the tumor immune microenvironment is also debatable. We conducted a prospective study to analyze the similarity in tumor immune microenvironments among different regions of a single tumor. METHODS: Multi-region sampling was performed on newly resected tumors. The tumor immune microenvironment was evaluated by immunohistochemical staining of PD-L1, CD4, CD8, CD20, FoxP3, DC-LAMP (or LAMP3), CD68, MPO, and tertiary lymphoid structures (TLSs). PD-L1 expression was manually quantified according to the percentage of PD-L1-stained tumor or stromal cells. The densities (number/mm2) of immune cells and the number of TLSs per sample were determined by whole-section counting. RNA-sequencing was applied in selected samples. Similarities in tumor immune microenvironments within each tumor were evaluated by multivariate Mahalanobis distance analyses. RESULTS: Thirteen tumors were collected from 12 patients. The median diameter of tumors was 9â¯cm (range 3-16â¯cm). A median of 6 samples (range 3-12) were obtained from each tumor. Nine (69.2%) tumors exhibited uniform expression of PD-L1 in all regions of the tumor. Out of 13 tumors analyzed by immunohistochemical staining, 8 (61.5%) tumors displayed a narrow Mahalanobis distance for all regions within the tumor; while 8 (66.7%) of the 12 tumors analyzed by RNA-sequencing displayed a narrow Mahalanobis distance. Immunohistochemistry and RNA-sequencing had a high concordance rate (83.3%; 10 of 12 tumors) for the evaluation of similarities between tumor immune microenvironments within a tumor. CONCLUSIONS: A single-region tumor sample might be reliable for the evaluation of tumor immune microenvironments in approximately 60-70% of patients with HCC. LAY SUMMARY: Heterogeneity in the regional immune microenvironments of tumors has been reported in patients with hepatocellular carcinoma. This heterogeneity could be an obstacle when trying to reliably evaluate the immune microenvironment of an entire tumor using only a single-region tumor sample, which may be the only option in patients with more advanced disease. Our study utilized both immunohistochemical and transcriptomic analyses to demonstrate that a single-region sample is reliable for evaluation of tumor immune microenvironments in 60-70% of patients with hepatocellular carcinoma.
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Antígeno B7-H1/metabolismo , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/metabolismo , Estructuras Linfoides Terciarias/inmunología , Microambiente Tumoral/inmunología , Adulto , Anciano , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/cirugía , Femenino , Humanos , Inmunohistoquímica/métodos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Linfocitos Infiltrantes de Tumor/inmunología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , RNA-Seq/métodos , Reproducibilidad de los Resultados , Linfocitos T/inmunología , TranscriptomaRESUMEN
BACKGROUND: There is currently no consensus regarding the relative applicability of minimally invasive treatment, including radiofrequency ablation (RFA) and minimally invasive surgery (MIS) in patients with a single small peripheral hepatocellular carcinoma (HCC) and compensated cirrhosis. This study investigated the clinical outcomes of MIS and RFA for single subcapsular HCC ≤ 2 cm in patients with compensated cirrhosis. METHODS: In this retrospective study, we enrolled 75 patients who had a single subcapsular HCC ≤ 2 cm along with Child-Pugh class A cirrhosis and a preoperative platelet count ≥ 100 k/µl. These patients underwent RFA (n = 39) or MIS (n = 36) between 2010 and 2016. Clinical outcomes including disease-free survival (DFS), survival without recurrence beyond the Milan criteria (RBM), and overall survival (OS) were compared. RESULTS: The 7-year DFS rates in the MIS and RFA groups were 86.1% and 35.9% (p < 0.001), respectively, the 7-year RBM rates were 88.9% and 66.7% (p = 0.014), respectively, and the 7-year OS rates were 97.2% and 82.1% (p = 0.008), respectively. RFA was associated with more ipsilateral lobe recurrence (20% vs. 83.4%, p = 0.004), and 40% were in direct contact with the ablation penumbra. A Cox proportional hazard analysis identified RFA as an independent predictor of mortality (adjusted hazard ratio, 9.625, p = 0.038). No major complications occurred in either group. RFA patients had a shorter hospital stay (median of 2 vs. 6 days, p < 0.001) and operation time (median of 23.5 vs. 216 min, p = 0.001). CONCLUSIONS: MIS was associated with a better 7-year OS, RBM, and DFS among patients with single subcapsular HCC ≤ 2 cm, Child-Pugh A liver function, and no clinically significant portal hypertension when compared to those who underwent percutaneous RFA.
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Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/cirugía , Ablación por Catéter , Cirrosis Hepática/complicaciones , Cirrosis Hepática/cirugía , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/cirugía , Procedimientos Quirúrgicos Mínimamente Invasivos , Ablación por Radiofrecuencia , Anciano , Supervivencia sin Enfermedad , Femenino , Hepatectomía , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Análisis Multivariante , Recurrencia Local de Neoplasia/cirugía , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
B-cell activating factor (BAFF) is found to be associated with the histological severity of nonalcoholic steatohepatitis (NASH). BAFF was also found to have a protective role in hepatic steatosis via down regulating the expression of steatogenesis genes and enhancing steatosis in hepatocytes through BAFF-R. However, the roles of BAFF during liver regeneration are not well defined. In this study, C57/B6 mice with 70% partial hepatectomy were used as a liver regeneration model. BAFF expression was determined by enzyme immunoassay, and anti-BAFF-neutralizing antibodies were administered to confirm the effects of BAFF on liver regeneration. Western blotting, immunohistochemistry, and florescence staining determined the expression of B-cell CCL/lymphoma 10 (BCL10). The angiogenesis promoting capability was evaluated after the transfection of cells with siRNA targeting BCL10 expression, and the role of NF-κB was assessed. The results revealed that the BAFF and BCL10 levels were upregulated after partial hepatectomy. Treatment with anti-BAFF-neutralizing antibodies caused death in mice that were subjected to 70% partial hepatectomy within 72 h. In vitro, recombinant BAFF protein did not enhance hepatocyte proliferation; however, transfection with BCL10 siRNA arrested hepatocytes at the G2/M phase. Interestingly, conditioned medium from BAFF-treated hepatocytes enhanced angiogenesis and endothelial cell proliferation. Moreover, Matrix metalloproteinase-9 (MMP-9), Fibroblast growth factor 4 (FGF4), and Interleukin-8 (IL-8) proteins were upregulated by BAFF through BCL10/NF-κB signaling. In mice that were treated with anti-BAFF-neutralizing antibodies, the microvessel density (MVD) of the remaining liver tissues and liver regeneration were both reduced. Taken together, our study demonstrated that an increased expression of BAFF and activation of BCL10/NF-κB signaling were involved in hepatocyte-driven angiogenesis and survival during liver regeneration.
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Factor Activador de Células B/metabolismo , Proteína 10 de la LLC-Linfoma de Células B/metabolismo , Hepatocitos/metabolismo , Regeneración Hepática/fisiología , FN-kappa B/metabolismo , Inductores de la Angiogénesis , Animales , Anticuerpos Neutralizantes , Factor Activador de Células B/inmunología , Proliferación Celular , Células Endoteliales , Factor 4 de Crecimiento de Fibroblastos/metabolismo , Hepatectomía , Hepatocitos/patología , Interleucina-8/metabolismo , Hígado/metabolismo , Hígado/patología , Regeneración Hepática/inmunología , Masculino , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones , Ratones Endogámicos C57BLRESUMEN
BACKGROUND: Research has revealed that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) may prevent cancers such as hepatocellular carcinoma (HCC). The comparative chemopreventive effects of ACEIs and ARBs in high-risk populations with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection have yet to be investigated. METHODS: From 2005 to 2014, high-risk HBV and HCV cohorts of hypertensive patients without HCC history were recruited from three linked national databases of Taiwan, and were classified into two groups based on the ACEI or ARB exposure within the initial six months after initiating antiviral agent. Intergroup differences in clinical characteristics and duration of drug exposure within study period were evaluated. HCC-free survival was compared using the log-rank test. Multivariate Cox regression including time-dependent variables for the use of ACEIs or ARBs and other medications was applied to adjust for confounders. RESULTS: Among the 7724 patients with HBV and 7873 with HCV, 46.3% and 42.5%, respectively, had an initial exposure to ACEIs or ARBs. The median durations of exposure were 36.4 and 38.9 months for the HBV and HCV cohorts, respectively. The median durations of ACEI or ARB use during study period between initial exposure and nonexposure groups were 41.8 vs. 18.3 months and 46.4 vs. 22.7 months for the HBV and HCV cohorts, respectively. No significant difference was observed in HCC risk within 7 years between the initial exposure and non-exposure groups. After adjustment for comorbidities, namely liver cirrhosis, diabetes mellitus (DM), and hyperlipidemia, and medications, namely aspirin, metformin, and statins, the hazard ratios (HRs) for ACEI or ARB exposure for HCC risk were 0.97 (95% confidence interval [CI]: 0.81-1.16) and 0.96 (0.80-1.16) in the HBV and HCV cohorts, respectively. In the HCV cohort, the increased HCC risk was associated with ACEI or ARB use in patients without cirrhosis, DM, and hyperlipidemia (HR: 4.53, 95% CI: 1.46-14.1). CONCLUSION: Compared with other significant risk and protective factors for HCC, ACEI or ARB use in the HBV and HCV cohorts was not associated with adequate protective effectiveness under standard dosages and may not be completely safe.
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Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Carcinoma Hepatocelular/prevención & control , Quimioprevención , Neoplasias Hepáticas/prevención & control , Anciano , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/mortalidad , Comorbilidad , Femenino , Estudios de Seguimiento , Hepatitis B/complicaciones , Hepatitis B/virología , Hepatitis C/complicaciones , Hepatitis C/virología , Humanos , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Liver recipients may develop various diseases after transplant. However, because of inadequate study of liver transplant during undergraduate education, the quality of post-transplant care provided to these patients remains suboptimal. Herein, we introduce an innovative and integrated multimodal pedagogical approach to effectively disseminate key information regarding liver transplant to undergraduate students. The goal is to examine this approach through students' assessment in multiple dimensions. METHODS: This prospective observational study evaluated student reactions to our pedagogical approach. Fifth-year medical students during the academic year 2015-2016 attended a 2-h session on what nontransplant doctors should know about liver transplants. The pedagogical strategy consisted of an online preclass self-learning exercise, an in-class interactive discussion (facilitated by the class teacher who is a liver transplant specialist to avoid distractions within the short-time frame), and a postclass essay assignment (to integrate and apply concepts). After the class, questionnaires were distributed to individual students to collect data, if returned, concerning the students' learning experience and feedback to improve teaching quality. Descriptive statistics, Mann-Whitney U tests, chi-squared tests, and McNemar's tests were used to analyze quantitative data. Qualitative data were content-coded through a descriptive approach using thematic analysis. RESULTS: Of the 266 attendees, 263 (98.9%) completed the questionnaires and 182 (69.2%) provided comments. Student feedback indicated they "felt better" and "more satisfied" compared with problem-based learning (PBL) (51.0 and 63.1%, respectively) or large-lecture class (92.0 and 88.6%, respectively) approaches. Regarding confidently managing liver transplant patients in future, 80 (30.4%) and 246 (93.5%) students expressed preclass and postclass confidence, respectively (p < 0.001). The bell curve of the postclass self-assessment score of learning shifted toward right and became steeper compared with that of the preclass score (p < 0.001), suggesting students acquired considerable knowledge. The course was typically perceived to be cost-effective, practical, tension-free, and student-friendly. CONCLUSION: This pedagogical approach effectively propagated knowledge concerning liver transplant to medical students, who expressed considerable satisfaction with the approach.
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Educación de Pregrado en Medicina , Trasplante de Hígado/educación , Aprendizaje Basado en Problemas , Calidad de la Atención de Salud , Estudiantes de Medicina , Femenino , Retroalimentación Formativa , Humanos , Aprendizaje , Masculino , Estudios Prospectivos , Encuestas y Cuestionarios , EnseñanzaRESUMEN
Right hepatectomy for a living liver donor via a pure minimally invasive approach is a challenging procedure and only a few cases have been reported. Between May 2013 and August 2015, 13 patients underwent robotic living donor right hepatectomy in our institute, and 54 patients received open surgery. In this series, no conversion was conducted for robotic donor right hepatectomy. The 2 groups shared similar blood loss (169 versus 146 mL), complication rates (7.7% versus 9.3%), and recovery of donor liver function (peak alanine aminotransferase, 269 versus 252 IU/mL). The robotic group needed longer operation time (596 versus 383 minutes) but less postoperative patient-controlled analgesia (0.58 versus 0.84 ng/kg) and a shorter period before returning to work/school (52.9 versus 100.0 days) and sex (100.0 versus 156.0 days). For recipient outcomes regarding the donor procedure, the robotic group shared similar experiences in early allograft dysfunction, complications, and 1-year recipient liver function with the open group. With respect to documented benefits of minimally invasive left-sided liver donor procedure, the development of right donor hepatectomy is slow. In conclusion, with substantial improvements in patient recovery after the minimally invasive approach, the robotic platform would be a big step toward completing pure minimally invasive liver donor surgery. Liver Transplantation 22 1509-1518 2016 AASLD.
Asunto(s)
Hepatectomía/métodos , Trasplante de Hígado/métodos , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Procedimientos Quirúrgicos Robotizados/métodos , Recolección de Tejidos y Órganos/métodos , Alanina Transaminasa/sangre , Analgesia Controlada por el Paciente , Aspartato Aminotransferasas/sangre , Pérdida de Sangre Quirúrgica , Estudios de Factibilidad , Femenino , Hepatectomía/efectos adversos , Humanos , Laparoscopía , Tiempo de Internación , Hígado/cirugía , Pruebas de Función Hepática , Donadores Vivos , Masculino , Procedimientos Quirúrgicos Mínimamente Invasivos/efectos adversos , Tempo Operativo , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Procedimientos Quirúrgicos Robotizados/efectos adversos , Factores de Tiempo , Recolección de Tejidos y Órganos/efectos adversosRESUMEN
The impact of the rate of intraportal hepatocyte transplantation on early engraftment and repopulation is unclear. The aim of this study was to address this and to improve the engraftment and repopulation efficiencies of hepatocyte transplantation for the treatment of a rat model of acute liver failure in a clinically useful way without preconditioning. Acute hepatic injury was induced into Sprague-Dawley rats with D-galactosamine. Hepatocytes were infused intraportally over a period of 30, 70, or 100 seconds to study early engraftment (2 days) and repopulation (7 days). Three groups had significant differences in hepatocyte engraftment (P = 0.018) and repopulation efficiencies (P = 0.037), and an infusion over a period of 70 seconds produced superior outcomes. After the 70-second infusion, the transplanted cells immediately transmigrated the sinusoidal endothelial layer and rarely accumulated in the portal venules, with liver function improving significantly. The mean first peak pressures, without significant differences, were 14.8 ± 6.5, 17.7 ± 3.7, and 13.6 ± 3.0 mm Hg in the 30-, 70-, and 100-second groups, respectively. Differential hepatocyte transfusion rates contributed to accelerated early engraftment and repopulation in rats with acute liver injury. These proof-of-concept findings are of clinical significance because they are easy to translate into practice.