RESUMEN
Uncontrolled bleeding during surgery is associated with high mortality and prolonged hospital stay, necessitating the use of hemostatic agents. Fibrin sealant patches offer an efficient solution to achieve hemostasis and improve patient outcomes in liver resection surgery. We have previously demonstrated the efficacy of a nanostructured fibrin-agarose hydrogel (NFAH). However, for the widespread distribution and commercialization of the product, it is necessary to develop an optimal preservation method that allows for prolonged stability and facilitates storage and distribution. We investigated cryopreservation as a potential method for preserving NFAH using trehalose. Structural changes in cryopreserved NFAH (Cryo-NFAH) were investigated and comparative in vitro and in vivo efficacy and safety studies were performed with freshly prepared NFAH. We also examined the long-term safety of Cryo-NFAH versus TachoSil in a rat partial hepatectomy model, including time to hemostasis, intra-abdominal adhesion, hepatic hematoma, inflammatory factors, histopathological variables, temperature and body weight, hemocompatibility and cytotoxicity. Structural analyses demonstrated that Cryo-NFAH retained most of its macro- and microscopic properties after cryopreservation. Likewise, hemostatic efficacy assays showed no significant differences with fresh NFAH. Safety evaluations indicated that Cryo-NFAH had a similar overall profile to TachoSil up to 40 days post-surgery in rats. In addition, Cryo-NFAH demonstrated superior hemostatic efficacy compared with TachoSil while also demonstrating lower levels of erythrolysis and cytotoxicity than both TachoSil and other commercially available hemostatic agents. These results indicate that Cryo-NFAH is highly effective hemostatic patch with a favorable safety and tolerability profile, supporting its potential for clinical use.
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Criopreservación , Hemostáticos , Hidrogeles , Nanoestructuras , Sefarosa , Animales , Hidrogeles/química , Hemostáticos/farmacología , Hemostáticos/química , Ratas , Sefarosa/química , Criopreservación/métodos , Nanoestructuras/química , Fibrina/química , Masculino , Hepatectomía/métodos , Humanos , Hemostasis/efectos de los fármacos , Ratas Sprague-DawleyRESUMEN
INTRODUCTION: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the third leading cause of cancer-related deaths worldwide. Hepatic resection is the treatment of choice for non-cirrhotic patients, while in cirrhotic individuals, the choice depends on tumor stage and liver function. METHODS: In this retrospective study conducted at Hospital El Cruce between 2015 and 2022, patients with HCC undergoing hepatic resection, both cirrhotic and non-cirrhotic, were evaluated. Morbidity, mortality, recurrence rate, and survival were analyzed. RESULTS: A total of 262 hepatectomies were performed, with 44 for HCC treatment. Among them, 35 were minor hepatectomies, and 9 were major hepatectomies (noncirrhotic patients). The majority were males (77%) with an average age of 58.5 years. Twenty-nine patients had cirrhosis, with hepatitis C (HCV) being the main cause in 48%, HCV with alcohol as a cofactor (21%), and alcohol alone (17%). Morbidity was 47.7%, with predominance of minor complications. Disease recurrence occurred in 59% of patients, and associated factors included tumor size and elevated AFP levels. Survival was better in cirrhotic patients compared to non-cirrhotic ones. DISCUSSION: Results tion 5837 Hepatic resection is an effective option for treating HCC in well-selected cirrhotic and non-cirrhotic patients, with encouraging results in terms of survival and disease control. Additionally, close surveillance for early recurrence detection and timely interventions is suggested.
Introducción: El carcinoma hepatocelular (HCC) es el cáncer primario más común del hígado y la tercera causa principal de muerte por cáncer en todo el mundo. La resección hepática es el tratamiento de elección para pacientes no cirróticos, mientras que, en cirróticos, la elección depende del estadio tumoral y la función hepática. Métodos: En este estudio retrospectivo realizado en el Hospital El Cruce entre 2015 y 2022, se evaluaron pacientes con HCC sometidos a resección hepática, tanto cirróticos como no cirróticos. Se analizó la morbimortalidad, la tasa de recurrencia y la sobrevida. Resultados: Se realizaron 262 hepatectomías, 44 fueron para tratamiento del HCC, de las cuales 35 fueron hepatectomías menores, y 9 hepatectomías mayores (no cirróticos). La mayoría eran hombres (77%) con una edad promedio de 58.5 años. Hubo 29 pacientes con cirrosis, siendo la hepatitis C (HCV) la causa principal en un 48%, HCV con alcohol como cofactor (21%) y alcohol (17%). La morbilidad fue del 47.7%, con complicaciones menores predominantes. La recurrencia de enfermedad ocurrió en el 59% de los pacientes, y los factores asociados incluyeron tamaño tumoral y niveles elevados de Alfafetoproteína. La supervivencia fue mejor en pacientes cirróticos en comparación con no cirróticos. Conclusión: La resección hepática es una opción efectiva para el tratamiento del HCC en pacientes bien seleccionados cirróticos y no cirróticos, con resultados alentadores en términos de supervivencia y control de la enfermedad. Además, se sugiere una vigilancia cercana para detectar recurrencias tempranas y proporcionar tratamientos oportunos.
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Carcinoma Hepatocelular , Hepatectomía , Cirrosis Hepática , Neoplasias Hepáticas , Recurrencia Local de Neoplasia , Humanos , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/mortalidad , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/mortalidad , Masculino , Hepatectomía/métodos , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Cirrosis Hepática/cirugía , Cirrosis Hepática/complicaciones , Adulto , Resultado del TratamientoAsunto(s)
Hepatectomía , Verde de Indocianina , Laparoscopía , Neoplasias Hepáticas , Imagen Óptica , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/diagnóstico por imagen , Humanos , Hepatectomía/métodos , Laparoscopía/métodos , Imagen Óptica/métodos , Hígado/diagnóstico por imagen , Hígado/cirugíaRESUMEN
Background: Hepatocyte nuclear factor 4 alpha (HNF4α) is the master regulator of hepatic differentiation. Recent studies have also revealed the role of HNF4α in hepatocyte proliferation via negatively regulating the expression of proto-mitogenic genes, including cMyc. Here, we aimed to study the interaction between HNF4α-cMyc during liver regeneration after partial hepatectomy (PHX). Methods: Wild-type (WT), hepatocyte-specific knockout of HNF4α (HNF4α-KO), cMyc (cMyc-KO), and HNF4α-cMyc double knockout (DKO) mice were subjected to PHX to induce liver regeneration. Blood and liver tissue samples were collected at 0h, 24h, 48h, 7D, and 14D after PHX for further analysis. Results: WT, HNF4α-KO, cMyc-KO and DKO mice regained liver weight by 14 days after PHX. The deletion of cMyc did not affect liver regeneration, which was similar to the WT mice. WT and cMyc-KO mice started regaining liver weight as early as 24 hours after PHX, with a peak proliferation response at 48 hours after PHX. HNF4α- KO and DKO showed a delayed response with liver weight increase by day 7 after PHX. The overall hepatocyte proliferation response by DKO mice following PHX was lower than that of other genotypes. Interestingly, the surviving HNF4α-KO and DKO mice showed re-expression of HNF4α at mRNA and protein levels on day 14 after PHX. This was accompanied by a significant increase in the expression of Krt19 and Epcam, hepatic progenitor cell markers, in the DKO mice on day 14 after PHX. Conclusion: These data indicate that, in the absence of HNF4α, cMyc contributes to hepatocyte-driven proliferation to compensate for the lost tissue mass. Furthermore, in the absence of both HNF4α and cMyc, HPC-driven proliferation occurs to support liver regeneration.
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Hepatectomía , Factor Nuclear 4 del Hepatocito , Regeneración Hepática , Ratones Noqueados , Animales , Regeneración Hepática/fisiología , Factor Nuclear 4 del Hepatocito/metabolismo , Factor Nuclear 4 del Hepatocito/genética , Ratones , Proliferación Celular , Proteínas Proto-Oncogénicas c-myc/metabolismo , Proteínas Proto-Oncogénicas c-myc/genética , Hepatocitos/metabolismo , Hígado/metabolismo , Masculino , Ratones Endogámicos C57BLRESUMEN
Intrahepatic cholangiocarcinoma (ICC) is the second commonly-seen liver malignancy and one of the most fatal cancers in Taiwan. Survival after diagnosis of ICC remains poor. This study aimed to investigate the survival and prognostic factors in patients with ICC. All patients with newly diagnosed ICC during 2004 to 2018 were identified from a national cancer database and followed until December 2020. Estimates of overall survival (OS) were conducted using the Kaplan-Meier method and Cox proportional hazards model. Hazard ratios with 95% confidence intervals were calculated. Initially, 7940 patients with ICC disease (stage IV: 55.6%, 4418/7940) were eligible for this study. Only 32.3% (2563/7940) patients with ICC underwent liver resection. After Propensity score matching, 969 pairs (N = 1938) of patients were matched and selected (mean age 62.8 ± 11.0 years, 53.1% were male, 29.7% had cirrhosis). The median follow-up time was 80.0 months (range 25-201 months). The 3-, 5-year OS rates were 44.0%, 36.4% in the surgical group and 26.0%, 23.7% in the non-surgical group, respectively. Surgery, young patients (≤ 54 years), small tumor size, no vascular invasion and chemotherapy were associated with better OS in patients with stages I-III disease. Surgery benefit was maximum in stage I disease followed by stage II. In patients with stage IV disease, factors such as surgery, young patients (≤ 64 years), single tumor, and no vascular invasion were associated with better OS. Chemotherapy was insignificantly associated with better OS. Long-term survival in patients with ICC is very poor. Compared to non-surgical patients, surgery conveys approximately 18% and 12% better OS rates at 3-year and 5-year, respectively. Early detection and surgical intervention may improve OS substantially in patients with ICC.
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Neoplasias de los Conductos Biliares , Colangiocarcinoma , Humanos , Colangiocarcinoma/mortalidad , Colangiocarcinoma/patología , Colangiocarcinoma/cirugía , Colangiocarcinoma/terapia , Masculino , Femenino , Persona de Mediana Edad , Neoplasias de los Conductos Biliares/mortalidad , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/cirugía , Neoplasias de los Conductos Biliares/terapia , Pronóstico , Anciano , Taiwán/epidemiología , Tasa de Supervivencia , Estimación de Kaplan-Meier , Modelos de Riesgos Proporcionales , Puntaje de Propensión , Estadificación de Neoplasias , HepatectomíaRESUMEN
PURPOSE: Multiple studies have reported models for predicting early recurrence of hepatocellular carcinoma (HCC) after liver resection (LR). However, these models are too complex to use in daily practice. We aimed to develop a simple model. METHOD: We enrolled 1133 patients with newly diagnosed HCC undergoing LR. The Kaplan - Meier method and log-rank test were used for survival analysis and Cox proportional hazards analysis to identify prognostic factors associated with early recurrence (i.e., recurrence within two years after LR). RESULTS: Early recurrence was identified in 403 (35.1%) patients. In multivariate analysis, alpha-fetoprotein (AFP) 20-399 vs. < 20 ng/ml (HR = 1.282 [95% confidence interval = 1.002-1.639]; p = 0.048); AFP ≥ 400 vs. < 20 ng/ml (HR = 1.755 [1.382-2.229]; p < 0.001); 7th edition American Joint Committee on Cancer (AJCC) stage 2 vs. 1 (HR = 1.958 [1.505-2.547]; p < 0.001); AJCC stage 3 vs. 1 (HR = 4.099 [3.043-5.520]; p < 0.001); and pathology-defined cirrhosis (HR = 1.46 [1.200-1.775]; p < 0.001) were associated with early recurrence. We constructed a predictive model with these variables, which provided three risk strata for recurrence-free survival (RFS): low risk, intermediate risk, and high risk, with two-year RFS of 79%, 57%, and 35%, respectively (p < 0.001). CONCLUSION: We developed a simple model to predict early recurrence risk for patients undergoing LR for HCC.
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Carcinoma Hepatocelular , Hepatectomía , Neoplasias Hepáticas , Recurrencia Local de Neoplasia , Humanos , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Recurrencia Local de Neoplasia/patología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Pronóstico , Estudios Retrospectivos , Adulto , Medición de Riesgo , Modelos de Riesgos Proporcionales , Estimación de Kaplan-Meier , Valor Predictivo de las Pruebas , Estadificación de NeoplasiasRESUMEN
BACKGROUND: To explore the capability of diffusion-based virtual MR elastography (vMRE) in the preoperative prediction of recurrence in hepatocellular carcinoma (HCC) and to investigate the underlying relevant histopathological characteristics. METHODS: Between August 2015 and December 2016, patients underwent preoperative MRI examination with a dedicated DWI sequence (b-values: 200,1500 s/mm2) were recruited. The ADC values and diffusion-based virtual shear modulus (µdiff) of HCCs were calculated and MR morphological features were also analyzed. The Cox proportional hazards model was used to identify the risk factors associated with tumor recurrence. A preoperative radiologic model and postoperative model including pathological features were built to predict tumor recurrence after hepatectomy. RESULTS: A total of 87 patients with solitary surgically confirmed HCCs were included in this study. Thirty-five patients (40.2%) were found to have tumor recurrence after hepatectomy. The preoperative model included higher µdiff and corona enhancement, while the postoperative model included higher µdiff, microvascular invasion, and histologic tumor grade. These factors were identified as significant prognostic factors for recurrence-free survival (RFS) (all p < 0.05). The HCC patients with µdiff values > 2.325 kPa showed poorer 5-year RFS after hepatectomy than patients with µdiff values ≤ 2.325 kPa (p < 0.001). Moreover, the higher µdiff values was correlated with the expression of CK19 (3.95 ± 2.37 vs. 3.15 ± 1.77, p = 0.017) and high Ki-67 labeling index (4.22 ± 1.63 vs. 2.72 ± 2.12, p = 0.001). CONCLUSIONS: The µdiff values related to the expression of CK19 and Ki-67 labeling index potentially predict RFS after hepatectomy in HCC patients.
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Carcinoma Hepatocelular , Diagnóstico por Imagen de Elasticidad , Hepatectomía , Neoplasias Hepáticas , Recurrencia Local de Neoplasia , Humanos , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/patología , Masculino , Diagnóstico por Imagen de Elasticidad/métodos , Femenino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico por imagen , Anciano , Imagen de Difusión por Resonancia Magnética/métodos , Adulto , Estudios Retrospectivos , PronósticoRESUMEN
OBJECTIVE: To assess the independent and combined associations of tumor-related psychiatric symptoms (TRPS) with dynamic health-related quality of life (HRQL) in patients with hepatocellular carcinoma (HCC) after hepatectomy and to identify related patterns of health behaviors. METHODS: This prospective study included patients with HCC who underwent hepatectomy between September 2021 and May 2022. Independent and combined associations between TRPS and HRQL were identified by generalized linear model and weighted quantile sum model, respectively. Trajectories of HRQL were identified by latent class mixed model. RESULTS: Among the 205 patients, 174 (84.9%) were male. For the outcome of HRQL at 6 months: Anxiety, depression, fatigue, and sleep disorder were independently associated with a decrease of HRQL (all P < 0.05). A negative combined effect of TRPS was also found (ß = - 5.07, 95% CI, - 10.01 to - 0.13), with depression emerged as the predominant contributor (49%). The health behaviors of body mass index, smoking, drinking, or physical exercise were not significantly modified the associations between combined TRPS and HRQL (all P > 0.05 for interaction). Similar results were also found for the HRQL at baseline and at 1 and 3 months. Three HRQL trajectory groups were identified: recover (44.9%), poor (44.4%), and deteriorating (10.7%). Deteriorating group was associated with higher incidence of TRPS (all P < 0.05). CONCLUSIONS: TRPS were associated with a decrease of HRQL regardless of healthy behaviors in HCC patients. Therefore, healthy behaviors promotion alone might not substantially increase HRQL associated with TRPS, and other measures tackling TRPS are warranted.
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Carcinoma Hepatocelular , Conductas Relacionadas con la Salud , Hepatectomía , Neoplasias Hepáticas , Calidad de Vida , Humanos , Masculino , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/psicología , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/psicología , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Hepatectomía/psicología , Hepatectomía/métodos , Anciano , Depresión/etiología , Depresión/epidemiología , AdultoRESUMEN
Surgical resection for localized hepatocellular carcinoma (HCC) is typically reserved for a minority of patients with favorable tumor features and anatomy. Neoadjuvant immunotherapy can expand the number of patients who are candidates for surgical resection and potentially reduce the chance for recurrence, but its role in HCC not defined. We retrospectively examined the outcomes of patients who underwent surgical resection for HCC at the Johns Hopkins Hospital and compared the clinical outcomes of patients who received neoadjuvant immunotherapy with those who underwent upfront resection. The clinical cohort included a total of 92 patients, 36 of whom received neoadjuvant immune checkpoint inhibitor (ICI)-based treatment. A majority of patients (61.1%) who received neoadjuvant ICI-based therapy were outside of standard resectability criteria and were more likely to have features known to confer risk of disease recurrence, including α-fetoprotein ≥ 400 ng/mL (P = 0.02), tumor diameter ≥ 5 cm (P = 0.001), portal vein invasion (P < 0.001), and multifocality (P < 0.001). Patients who received neoadjuvant immunotherapy had similar rates of margin-negative resection (P = 0.47) and recurrence-free survival (RFS) as those who underwent upfront surgical resection (median RFS 44.8 months compared with 49.3 months, respectively, log-rank P = 0.66). There was a nonsignificant trend toward superior RFS in the subset of patients with a pathologic response (tumor necrosis ≥ 70%) with neoadjuvant immunotherapy. Neoadjuvant ICI-based therapy may allow high-risk patients, including those who are outside traditional resectability criteria, to achieve comparable clinical outcomes with those who undergo upfront resection. SIGNIFICANCE: Surgical resection for localized HCC is typically only reserved for those with solitary tumors without vascular invasion. In this retrospective analysis, we show that neoadjuvant immunotherapy may allow high-risk patients, including those who are outside of standard resection criteria, to undergo successful margin-negative resection and achieve comparable long-term clinical outcomes compared with upfront resection. These findings highlight need for prospective studies on neoadjuvant immunotherapy in HCC.
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Carcinoma Hepatocelular , Inmunoterapia , Neoplasias Hepáticas , Terapia Neoadyuvante , Recurrencia Local de Neoplasia , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/inmunología , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/inmunología , Terapia Neoadyuvante/métodos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Inmunoterapia/métodos , Recurrencia Local de Neoplasia/prevención & control , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Supervivencia sin Enfermedad , HepatectomíaRESUMEN
Liver fibrosis progressing to cirrhosis is a major risk factor for liver cancer, impacting surgical treatment and survival. Our study focuses on the role of extracellular nicotinamide adenine dinucleotide (eNAD+) in liver fibrosis, analyzing liver disease patients undergoing surgery. Additionally, we explore NAD+'s therapeutic potential in a mouse model of extended liver resection and in vitro using 3D hepatocyte spheroids. eNAD+ correlated with aspartate transaminase (AST) and bilirubin after liver resection (AST: r = 0.2828, p = 0.0087; Bilirubin: r = 0.2584, p = 0.0176). Concordantly, post-hepatectomy liver failure (PHLF) was associated with higher eNAD+ peaks (n = 10; p = 0.0063). Post-operative eNAD+ levels decreased significantly (p < 0.05), but in advanced stages of liver fibrosis or cirrhosis, this decline not only diminished but actually showed a trend towards an increase. The expression of NAD+ biosynthesis rate-limiting enzymes, nicotinamide phosphoribosyltransferase (NAMPT) and nicotinamide mononucleotide adenylyltransferase 3 (NMNAT3), were upregulated significantly in the liver tissue of patients with higher liver fibrosis stages (p < 0.0001). Finally, the administration of NAD+ in a 3D hepatocyte spheroid model rescued hepatocytes from TNFalpha-induced cell death and improved viability (p < 0.0001). In a mouse model of extended liver resection, NAD+ treatment significantly improved survival (p = 0.0158) and liver regeneration (p = 0.0186). Our findings reveal that eNAD+ was upregulated in PHLF, and rate-limiting enzymes of NAD+ biosynthesis demonstrated higher expressions under liver fibrosis. Further, eNAD+ administration improved survival after extended liver resection in mice and enhanced hepatocyte viability in vitro. These insights may offer a potential target for future therapies.
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Hepatectomía , Fallo Hepático , NAD , NAD/metabolismo , Animales , Humanos , Ratones , Fallo Hepático/etiología , Fallo Hepático/metabolismo , Fallo Hepático/patología , Fallo Hepático/cirugía , Masculino , Hepatocitos/metabolismo , Persona de Mediana Edad , Femenino , Ratones Endogámicos C57BL , Cirrosis Hepática/metabolismo , Cirrosis Hepática/cirugía , Modelos Animales de Enfermedad , AncianoRESUMEN
BACKGROUND: Surgical resection remains the cornerstone of treatment for hepatoblastoma in children and offers the best chance of disease-free survival. We aimed to analyze the 30 day outcomes of hepatic resection for hepatoblastoma stratified by extent using the National Surgical Quality Improvement Program-Pediatric (NSQIP-P). METHODS: We queried NSQIP-P for children undergoing resection of Hepatoblastoma from 2012 to 2021. Relevant clinical characteristics and outcomes were extracted for multivariate logistic regression to identify predictors of common adverse outcomes. RESULTS: We included 458 children with a median age of 1.90 years. Overall complications were rare, and perioperative blood transfusion (64.2%) and postoperative ventilation > 48 h (10.0%) were the only adverse events prevalent in more than 5% of patients. Median transfusion volume was 15.7 ml/kg. On multivariate regression, only patients undergoing Trisectionectomy (aOR = 3.387, 95% C.I. = 1.348-8.510) had higher odds of receiving > 75th percentile blood transfusion. Furthermore, only perioperative transfusion and postoperative ventilation > 48 h were statistically more common in patients undergoing extended versus standard resections. CONCLUSIONS: Outcomes following resection of hepatoblastoma are excellent, with low rates of postoperative adverse events. Although children undergoing trisectionectomy likely require greater transfusion volume, extended hepatic resections do not appear to have worse 30 day outcomes despite greater operative complexity and duration.
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Bases de Datos Factuales , Hepatectomía , Hepatoblastoma , Neoplasias Hepáticas , Complicaciones Posoperatorias , Mejoramiento de la Calidad , Humanos , Hepatoblastoma/cirugía , Neoplasias Hepáticas/cirugía , Femenino , Lactante , Hepatectomía/métodos , Masculino , Preescolar , Niño , Complicaciones Posoperatorias/epidemiología , Resultado del Tratamiento , Estudios Retrospectivos , Transfusión Sanguínea/estadística & datos numéricos , Estados UnidosAsunto(s)
Carcinoma Hepatocelular , Hepatectomía , Hipertensión Portal , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/cirugía , Carcinoma Hepatocelular/cirugía , Hipertensión Portal/cirugía , Hepatectomía/efectos adversos , Estudios Prospectivos , Complicaciones Posoperatorias/etiología , Resultado del Tratamiento , Estudios de CohortesRESUMEN
PURPOSE: Single large hepatocellular carcinoma >5cm (SLHCC) traditionally requires a major liver resection. Minor resections are often performed with the goal to reduce morbidity and mortality. Aim of the study was to establish if a major resection should be considered the best treatment for SLHCC or a more limited resection should be preferred. METHODS: A multicenter retrospective analysis of the HE.RC.O.LE.S. Group register was performed. All collected patients with surgically treated SLHCC were divided in 5 groups of treatment (major hepatectomy, sectorectomy, left lateral sectionectomy, segmentectomy, non-anatomical resection) and compared for baseline characteristics, short and long-term results. A propensity-score weighted analysis was performed. RESULTS: 535 patients were enrolled in the study. Major resection was associated with significantly increased major complications compared to left lateral sectionanectomy, segmentectomy and non-anatomical resection (all p<0.05) and borderline significant increased major complications compared to sectorectomy (p=0.08). Left lateral sectionectomy showed better overall survival compared to major resection (p=0.02), while other groups of treatment resulted similar to major hepatectomy group for the same item. Absence of oncological benefit after major resection and similar outcomes among the 5 groups of treatment was confirmed even in the sub-population excluding patients with macrovascular invasion. CONCLUSION: Major resection was associated to increased major post-operative morbidity without long-term survival benefit; when technically feasible and oncologically adequate, minor resections should be preferred for the surgical treatment of SLHCC.
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Carcinoma Hepatocelular , Hepatectomía , Neoplasias Hepáticas , Puntaje de Propensión , Humanos , Hepatectomía/métodos , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/mortalidad , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/mortalidad , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Complicaciones Posoperatorias/etiología , Resultado del Tratamiento , Tasa de Supervivencia , AdultoRESUMEN
BACKGROUND: Laparoscopic liver surgery is increasingly used for more challenging procedures. The aim of this study was to assess the feasibility and oncological safety of laparoscopic right hepatectomy for colorectal liver metastases after portal vein embolization. METHODS: This was an international retrospective multicentre study of patients with colorectal liver metastases who underwent open or laparoscopic right and extended right hepatectomy after portal vein embolization between 2004 and 2020. The perioperative and oncological outcomes for patients who underwent laparoscopic and open approaches were compared using propensity score matching. RESULTS: Of 338 patients, 84 patients underwent a laparoscopic procedure and 254 patients underwent an open procedure. Patients in the laparoscopic group less often underwent extended right hepatectomy (18% versus 34.6% (P = 0.004)), procedures in the setting of a two-stage hepatectomy (42% versus 65% (P < 0.001)), and major concurrent procedures (4% versus 16.1% (P = 0.003)). After propensity score matching, 78 patients remained in each group. The laparoscopic approach was associated with longer operating and Pringle times (330 versus 258.5 min (P < 0.001) and 65 versus 30 min (P = 0.001) respectively) and a shorter length of stay (7 versus 8 days (P = 0.011)). The R0 resection rate was not different (71% for the laparoscopic approach versus 60% for the open approach (P = 0.230)). The median disease-free survival was 12 (95% c.i. 10 to 20) months for the laparoscopic approach versus 20 (95% c.i. 13 to 31) months for the open approach (P = 0.145). The median overall survival was 28 (95% c.i. 22 to 48) months for the laparoscopic approach versus 42 (95% c.i. 35 to 52) months for the open approach (P = 0.614). CONCLUSION: The advantages of a laparoscopic over an open approach for (extended) right hepatectomy for colorectal liver metastases after portal vein embolization are limited.
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Neoplasias Colorrectales , Embolización Terapéutica , Hepatectomía , Laparoscopía , Neoplasias Hepáticas , Vena Porta , Humanos , Hepatectomía/métodos , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Neoplasias Colorrectales/patología , Laparoscopía/métodos , Masculino , Femenino , Vena Porta/cirugía , Embolización Terapéutica/métodos , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Puntaje de Propensión , Resultado del Tratamiento , Estudios de Factibilidad , Tiempo de InternaciónRESUMEN
Background: The liver's regenerative capacity allows it to repair itself after injury. Extracellular vesicles and particles (EVPs) in the liver's interstitial space are crucial for signal transduction, metabolism, and immune regulation. Understanding the role and mechanism of liver-derived EVPs in regeneration is significant, particularly after partial hepatectomy, where the mechanisms remain unclear. Methods: A 70% hepatectomy model was established in mice, and EVPs were isolated and characterized using electron microscopy, nanocharacterization, and Western blot analysis. Combined metabolomic and transcriptomic analyses revealed ß-sitosterol enrichment in EVPs and activation of the Hedgehog signaling pathway during regeneration. The role of ß-sitosterol in EVPs on the Hedgehog pathway and its targets were identified using qRT-PCR, Western blot analysis. The regulation of carnitine synthesis by this pathway was determined using a dual luciferase assay. The effect of a ß-sitosterol diet on liver regeneration was verified in mice. Results: After 70% hepatectomy, the liver successfully regenerated without liver failure or death. At 24 hours post-surgery, tissue staining showed transient regeneration-associated steatosis (TRAS), with increased Ki67 positivity at 48 hours. EVPs displayed a spherical lipid bilayer structure with particle sizes of 70-130 nm. CD9, CD63, and CD81 in liver-derived EVPs were confirmed. Transcriptomic and metabolomic analyses showed EVPs supplementation significantly promoted carnitine synthesis and fatty acid oxidation. Tissue staining confirmed accelerated TRAS resolution and enhanced liver regeneration with EVP supplementation. Mass spectrometry identified ß-sitosterol in EVPs, which binds to Smo protein, activating the Hedgehog pathway. This led to the nuclear transport of Gli3, stimulating Setd5 transcription and inducing carnitine synthesis, thereby accelerating fatty acid oxidation. Mice with increased ß-sitosterol intake showed faster TRAS resolution and liver regeneration compared to controls. Conclusion: Liver-derived EVPs promote regeneration after partial hepatectomy. ß-sitosterol from EVPs accelerates fatty acid oxidation and promotes liver regeneration by activating Hedgehog signaling pathway.
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Vesículas Extracelulares , Proteínas Hedgehog , Hepatectomía , Regeneración Hepática , Hígado , Sitoesteroles , Animales , Sitoesteroles/farmacología , Sitoesteroles/química , Regeneración Hepática/efectos de los fármacos , Regeneración Hepática/fisiología , Vesículas Extracelulares/efectos de los fármacos , Vesículas Extracelulares/química , Ratones , Hígado/efectos de los fármacos , Hígado/metabolismo , Proteínas Hedgehog/metabolismo , Masculino , Transducción de Señal/efectos de los fármacos , Ratones Endogámicos C57BL , Carnitina/farmacología , Tamaño de la PartículaRESUMEN
PURPOSE: Recently, children with trisomy 18 have been receiving more active treatment for malignancies. We report herein seven cases complete resection was achieved, and discuss multidisciplinary treatment for hepatoblastoma in patients with trisomy 18. METHOD: The medical records of children with trisomy 18 who were treated at the study center between 2010 and 2023 were reviewed. RESULT: Six of 69 patients had hepatoblastoma development, and three of these underwent multidisciplinary treatment. In addition, 6 patients had been referred by another hospital for treatment, and four of these underwent multidisciplinary treatment. Among the seven patients who underwent multidisciplinary treatment, three, two, and two were categorized in Pre-treatment Extent of Disease (PRETEXT) classification group I, II, and III, respectively. Neoadjuvant chemotherapy resulting in tumor reduction was performed in three cases. In all the cases, complete resection was achieved with pathologically safe margins. Perioperative complications included circulatory failure in one case and bile leakage in two cases. Adjuvant chemotherapy was administered in four cases. The postoperative observation period ranged from 3 months to 11 years, and all the patients are recurrence-free. CONCLUSION: Children with trisomy 18 complicated with hepatoblastoma whose cardiopulmonary conditions are stable may be good candidates for chemotherapy and surgery.
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Hepatoblastoma , Neoplasias Hepáticas , Síndrome de la Trisomía 18 , Humanos , Hepatoblastoma/genética , Hepatoblastoma/cirugía , Síndrome de la Trisomía 18/complicaciones , Síndrome de la Trisomía 18/genética , Síndrome de la Trisomía 18/cirugía , Masculino , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/genética , Femenino , Lactante , Preescolar , Estudios Retrospectivos , Hepatectomía/métodos , Niño , Resultado del Tratamiento , Trisomía/genéticaRESUMEN
PURPOSE: The technical difficulties of laparoscopic liver resection (LLR) are greatly associated with the location of liver tumors. Since segment 8 (S8) contains a wide area, the difficulty of LLR for S8 tumors may vary depending on the location within the segment, such as the ventral (S8v) and dorsal (S8d) area, but the difference is unclear. METHODS: We retrospectively investigated 30 patients who underwent primary laparoscopic partial liver resection for liver tumors in S8 at Kobe University Hospital between January 2018 and June 2023. RESULTS: Thirteen and 17 patients underwent LLR for S8v and S8d, respectively. The operation time was significantly longer (S8v 203[135-259] vs. S8d 261[186-415] min, P = 0.002) and the amount of blood loss was significantly higher (10[10-150] vs. 10[10-200] mL, P = 0.034) in the S8d group than in the S8v group. No significant differences were observed in postoperative complications or postoperative length of hospital stay. Additionally, intraoperative findings revealed that the rate at which the case performed partial liver mobilization in the S8d group was higher (2[15.4%] vs. 8[47.1%], P = 0.060) and the median parenchymal transection time of the S8d group was longer (102[27-148] vs. 129[37-175] min, P = 0.097) than those in the S8v group, but there were no significant differences. CONCLUSION: The safety of LLR for the S8d was comparable to that of LLR for S8v, although LLR for S8d resulted in longer operative time and more blood loss. THE TRIAL REGISTRATION NUMBER: B230165 (approved at December 26, 2023).
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Hepatectomía , Laparoscopía , Neoplasias Hepáticas , Tempo Operativo , Humanos , Masculino , Femenino , Hepatectomía/métodos , Laparoscopía/métodos , Estudios Retrospectivos , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/patología , Persona de Mediana Edad , Anciano , Tiempo de Internación/estadística & datos numéricos , Pérdida de Sangre Quirúrgica/estadística & datos numéricos , Complicaciones Posoperatorias/etiología , Adulto , Resultado del TratamientoAsunto(s)
Hepatectomía , Laparoscopía , Cirujanos , Humanos , Estudios Retrospectivos , Laparoscopía/estadística & datos numéricos , Hepatectomía/estadística & datos numéricos , Hepatectomía/métodos , Femenino , Masculino , Persona de Mediana Edad , Cirujanos/estadística & datos numéricos , Anciano , Neoplasias Hepáticas/cirugíaRESUMEN
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
BACKGROUND: Hepatic alveolar echinococcosis (AE) is a severe zoonotic parasitic disease, and accurate preoperative prediction of lymph node (LN) metastasis in AE patients is crucial for disease management, but it remains an unresolved challenge. The aim of this study was to establish a radiomics model for the preoperative prediction of LN metastasis in hepatic AE patients. METHODS: A total of 100 hepatic AE patients who underwent hepatectomy and hepatoduodenal ligament LN dissection at Qinghai Provincial People's Hospital between January 2016 and August 2023 were included in the study. The patients were randomly divided into a training set and a validation set at an 8:2 ratio. Radiomic features were extracted from three-dimensional images of the hepatoduodenal ligament LNs delineated on arterial phase computed tomography (CT) scans of hepatic AE patients. Least absolute shrinkage and selection operator (LASSO) regression was applied for data dimensionality reduction and feature selection. Multivariate logistic regression analysis was performed to develop a prediction model, and the predictive performance of the model was evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). RESULTS: A total of 7 radiomics features associated with LN status were selected using LASSO regression. The classification performances of the training set and validation set were consistent, with area under the operating characteristic curve (AUC) values of 0.928 and 0.890, respectively. The model also demonstrated good stability in subsequent validation. CONCLUSION: In this study, we established and evaluated a radiomics-based prediction model for LN metastasis in patients with hepatic AE using CT imaging. Our findings may provide a valuable reference for clinicians to determine the occurrence of LN metastasis in hepatic AE patients preoperatively, and help guide the implementation of individualized surgical plans to improve patient prognosis.