A preoperative risk score based on early recurrence for estimating outcomes after resection of hepatocellular carcinoma in the non-cirrhotic liver.

BACKGROUND: Liver resection is the mainstay treatment option for patients with hepatocellular carcinoma in the non-cirrhotic liver (NCL-HCC), but almost half of these patients will experience a recurrence within five years of surgery. Therefore, we aimed to develop a rationale-based risk evaluation tool to assist surgeons in recurrence-related treatment planning for NCL-HCC. METHODS: We analyzed single-center data from 263 patients who underwent liver resection for NCL-HCC. Using machine learning modeling, we first determined an optimal cut-off point to discriminate early versus late relapses based on time to recurrence. We then constructed a risk score based on preoperative variables to forecast outcomes according to recurrence-free survival. RESULTS: We computed an optimal cut-off point for early recurrence at 12 months post-surgery. We identified macroscopic vascular invasion, multifocal tumor, and spontaneous tumor rupture as predictor variables of outcomes associated with early recurrence and integrated them into a scoring system. We thus stratified, with high concordance, three groups of patients on a graduated scale of recurrence-related survival. CONCLUSION: We constructed a preoperative risk score to estimate outcomes after liver resection in NCL-HCC patients. Hence, this score makes it possible to rationally stratify patients based on recurrence risk assessment for better treatment planning.

Toxicity assessment of synthetic chalcones with antileishmanial potential in BALB/c mice. / Evaluación de la toxicidad de chalconas sintéticas con potencial anti-Leishmania en ratones BALB/c.

OBJECTIVE: To evaluate the toxicity of three synthetic chalcones administered intraperitoneally to BALB/c mice. MATERIALS AND METHODS: The median lethal dose (LD50) was estimated by Dixon's Up-and-Down method. Subchronic toxicity of chalcones was evaluated at 20 and 40 mg/kg for 21 days. Behavioral, physiological, biochemical, and histological toxic effects were evaluated. RESULTS: Chalcone 43 produced mucus in feces, visceral damage (liver) and alterations in organ coefficient (kidney, p = 0.037 and brain, p = 0.008) when compared to the control group. In addition, histological analysis showed that this chalcone produced edema, inflammation and necrosis in the evaluated organs, although there was no significant difference with the control. None of the biochemical parameters differed significantly between the treatment groups at 40 mg/kg dose and the control. CONCLUSIONS: The LD50 for all three chalcones was greater than 550 mg/kg of body weight. Chalcones 40 and 42 were found to be relatively non-toxic. Both can be considered safe for intraperitoneal application in BALB/c mice and, consequently, are potential candidates for use in the treatment of leishmaniasis.

OBJETIVO: Evaluar la toxicidad de tres chalconas sintéticas administradas por vía intraperitoneal en ratones BALB/c. MATERIALES Y MÉTODOS: La dosis letal media (DL50) se estimó por el método Up-and-Down de Dixon. La toxicidad subcrónica de las chalconas se evaluó a 20 y 40   mg/kg por 21 días. Se evaluó el efecto tóxico a nivel de comportamiento, fisiológico, bioquímico e histológico. RESULTADOS: La chalcona 43 generó moco en las heces, daño visceral (hígado) y alteración en el coeficiente de órganos (riñón, p   =   0,037 y cerebro, p   =   0,008) en comparación con el grupo control. Además, en el análisis histológico se observó que esta chalcona produjo edema, inflamación y necrosis en los órganos evaluados, aunque no hubo diferencia significativa con el control. Todos los parámetros bioquímicos no difirieron significativamente entre los grupos de tratamiento a dosis de 40   mg/kg y el control. CONCLUSIONES: La DL50 para las tres chalconas fue superior a 550   mg/kg de peso corporal. Las chalconas 40 y 42 son relativamente no tóxicas. Ambas pueden considerarse seguras para la aplicación vía intraperitoneal en ratones BALB/c y, en consecuencia, son posibles candidatas para ser usadas en el tratamiento contra las leishmaniosis.

Evaluación de la toxicidad de chalconas sintéticas con potencial anti-Leishmania en ratones BALB/c / Toxicity assessment of synthetic chalcones with antileishmanial potential in BALB/c mice

RESUMEN Objetivo: Evaluar la toxicidad de tres chalconas sintéticas administradas por vía intraperitoneal en ratones BALB/c. Materiales y métodos: La dosis letal media (DL50) se estimó por el método Up-and-Down de Dixon. La toxicidad subcrónica de las chalconas se evaluó a 20 y 40 mg/kg por 21 días. Se evaluó el efecto tóxico a nivel de comportamiento, fisiológico, bioquímico e histológico. Resultados: La chalcona 43 generó moco en las heces, daño visceral (hígado) y alteración en el coeficiente de órganos (riñón, p = 0,037 y cerebro, p = 0,008) en comparación con el grupo control. Además, en el análisis histológico se observó que esta chalcona produjo edema, inflamación y necrosis en los órganos evaluados, aunque no hubo diferencia significativa con el control. Todos los parámetros bioquímicos no difirieron significativamente entre los grupos de tratamiento a dosis de 40 mg/kg y el control. Conclusiones: La DL50 para las tres chalconas fue superior a 550 mg/kg de peso corporal. Las chalconas 40 y 42 son relativamente no tóxicas. Ambas pueden considerarse seguras para la aplicación vía intraperitoneal en ratones BALB/c y, en consecuencia, son posibles candidatas para ser usadas en el tratamiento contra las leishmaniosis.

ABSTRACT Objective: To evaluate the toxicity of three synthetic chalcones administered intraperitoneally to BALB/c mice. Materials and methods: The median lethal dose (LD50) was estimated by Dixon's Up-and-Down method. Subchronic toxicity of chalcones was evaluated at 20 and 40 mg/kg for 21 days. Behavioral, physiological, biochemical, and histological toxic effects were evaluated. Results: Chalcone 43 produced mucus in feces, visceral damage (liver) and alterations in organ coefficient (kidney, p = 0.037 and brain, p = 0.008) when compared to the control group. In addition, histological analysis showed that this chalcone produced edema, inflammation and necrosis in the evaluated organs, although there was no significant difference with the control. None of the biochemical parameters differed significantly between the treatment groups at 40 mg/kg dose and the control. Conclusions: The LD50 for all three chalcones was greater than 550 mg/kg of body weight. Chalcones 40 and 42 were found to be relatively non-toxic. Both can be considered safe for intraperitoneal application in BALB/c mice and, consequently, are potential candidates for use in the treatment of leishmaniasis.