Hepatocellular carcinoma: A real-life experience in a specialized center in Bogotá, Colombia / Hepatocarcinoma: experiencia de la vida real en un centro especializado de Bogotá, Colombia

Abstract Introduction: Hepatocellular carcinoma (HCC) is the most frequent malignant primary liver tumor globally. In 2018, it ranked sixth and represented the fourth cause of death from cancer; the five-year overall survival is 18 %. Most cases of HCC develop in patients with cirrhosis of any etiology, especially because of hepatitis B and C viruses, alcohol, and recently nonalcoholic steatohepatitis (NASH). Aim: To analyze the clinical characteristics, diagnostic methods, treatments, prognostic variables, and survival. Materials and methods: This retrospective descriptive study was conducted on a cohort of patients diagnosed with cirrhosis and treated between January 2011 and December 2020 at a health care center in Bogotá. The diagnosis of HCC was confirmed radiologically or by biopsy. We analyzed the information descriptively with absolute frequency measures in the case of categorical variables. For continuous variables, the information was summarized with measures of central tendency (mean or median) and their relevant measures of dispersion. Results: We included 152 patients diagnosed with HCC, with a mean age of 69.4 years; 51.3 % were men. The leading cause of HCC was nonalcoholic fatty liver disease (NAFLD), which accounted for almost a third of cases (32 %); other causes were alcohol (15 %) and hepatitis C virus (14 %). The median manifestation of the tumor was two nodules with a size close to 4 cm. Besides, 35 % of patients had a BCLC (Barcelona Clinic Liver Cancer) stage with curative options, and 25 % received curative treatment options. The first-line systemic therapy used in this cohort was sorafenib®, used in 35 patients (33.7 %). Survival curves showed that women, Child-Pugh class A, and BCLC stage 0 had higher median survival. Multivariate analysis showed a higher risk of death for males (hazard ratio [HR]: 2.16; confidence interval [CI]: 1.24-3.76), Child-Pugh class B (HR: 2.14; CI 1.16-3.95), and Child-Pugh class C (HR: 7.52; CI 2.88-19.57). Conclusions: NAFLD is the leading cause of HCC in this cohort. A third of patients are diagnosed in early BCLC stages with a curative treatment option, and 25 % are treated with curative therapies. Sorafenib was the first-line therapy in advanced HCC. Overall survival after diagnosis of HCC remains low, being necessary to join forces in the follow-up of patients with cirrhosis to improve these outcomes.

Resumen Introducción: el hepatocarcinoma (HCC) es el tumor hepático primario maligno más frecuente en el mundo: en 2018 ocupó la sexta posición y representó la cuarta causa de muerte por cáncer; la supervivencia global a 5 años es del 18 %. La mayoría de los casos de HCC se desarrolla en pacientes con cirrosis de cualquier etiología, especialmente por virus de la hepatitis B y C, alcohol y, recientemente, por la esteatohepatitis no alcohólica (NASH). Objetivo: analizar las características clínicas, métodos de diagnóstico, tratamientos, variables pronósticas y supervivencia. Metodología: estudio descriptivo retrospectivo de una cohorte de pacientes con diagnóstico de cirrosis atendidos entre enero de 2011 y diciembre de 2020 en un centro de atención médica de Bogotá, con diagnóstico de HCC confirmado radiológicamente o por biopsia. La información se analizó de forma descriptiva con medidas de frecuencia absoluta en el caso de las variables categóricas; para las variables continuas se resumió la información con medidas de tendencia central (media o medianas) y su respectiva medida de dispersión. Resultados: se incluyeron 152 pacientes diagnosticados con HCC, con edad promedio de 69,4 años, 51,3 % eran hombres. La principal causa de HCC fue el hígado graso no alcohólico (NAFLD), que representó casi una tercera parte de los casos (32 %); otras causas fueron el alcohol (15 %) y el virus de la hepatitis C (14 %). La mediana de presentación del tumor fue de 2 nódulos con un tamaño cercano a 4 cm. El 35 % de los pacientes tenía un estadio BCLC (Barcelona Clinic Liver Cancer) con opciones curativas y el 25 % de los pacientes recibió opciones curativas de tratamiento. La terapia sistémica de primera línea utilizada en esta cohorte fue el sorafenib®, que se utilizó en 35 pacientes (33,7 %). Las curvas de supervivencia mostraron que las mujeres, el estadio Child-Pugh A y el estadio BCLC 0 presentaron mayores medianas de supervivencia. El análisis multivariado evidenció un mayor riesgo de muerte al ser hombre (Hazard ratio [HR]: 2,16; intervalo de confianza [IC]: 1,24 a 3,76), estar en los estadios Child-Pugh B (HR: 2,14; IC: 1,16 a 3,95) y Child-Pugh C (HR: 7,52; IC: 2,88 a 19,57). Conclusiones: el NAFLD es la principal causa de HCC en la presente cohorte, una tercera parte de los pacientes se diagnostica en estadios BCLC tempranos con opción curativa de tratamiento, y un 25 % se trata con terapias curativas. El sorafenib fue la terapia de primera línea en HCC avanzado. La supervivencia global luego del diagnóstico de HCC sigue siendo baja, y es necesario aunar esfuerzos en el seguimiento de los pacientes con cirrosis para mejorar estos resultados.

Serum mitochondrial tsRNA serves as a novel biomarker for hepatocarcinoma diagnosis / 医学前沿

Hepatocellular carcinoma (HCC), which makes up the majority of liver cancer, is induced by the infection of hepatitis B/C virus. Biomarkers are needed to facilitate the early detection of HCC, which is often diagnosed too late for effective therapy. The tRNA-derived small RNAs (tsRNAs) play vital roles in tumorigenesis and are stable in circulation. However, the diagnostic values and biological functions of circulating tsRNAs, especially for HCC, are still unknown. In this study, we first utilized RNA sequencing followed by quantitative reverse-transcription PCR to analyze tsRNA signatures in HCC serum. We identified tRF-Gln-TTG-006, which was remarkably upregulated in HCC serum (training cohort: 24 HCC patients vs. 24 healthy controls). In the validation stage, we found that tRF-Gln-TTG-006 signature could distinguish HCC cases from healthy subjects with high sensitivity (80.4%) and specificity (79.4%) even in the early stage (Stage I: sensitivity, 79.0%; specificity, 74.8%; 155 healthy controls vs. 153 HCC patients from two cohorts). Moreover, in vitro studies indicated that circulating tRF-Gln-TTG-006 was released from tumor cells, and its biological function was predicted by bioinformatics assay and validated by colony formation and apoptosis assays. In summary, our study demonstrated that serum tsRNA signature may serve as a novel biomarker of HCC.

Presentaciones infrecuentes y atípicas del carcinoma hepatocelular en tomografía computarizada y resonancia magnética / Rare and atypical presentations of hepatocellular carcinoma on CT and MRI

Resumen La apariencia en imágenes típicas del carcinoma hepatocelular (HCC) es ampliamente reconocida y consiste en hiperrealce en fase arterial con lavado en las fases venosa portal y tardía, tanto en tomografía computada como en resonancia magnética. Este patrón se observa en el 60% de los casos y se ha incorporado en las directrices diagnósticas de las diferentes organizaciones que participan en el estudio de las enfermedades hepáticas y su presencia evita la necesidad de una biopsia. Además, son signos auxiliares útiles en el diagnóstico del HCC la hiperintensidad en secuencias ponderadas en T2, la presencia de grasa, la trombosis tumoral venosa y el crecimiento entre intervalos en los estudios de seguimiento. Sin embargo, no todos los pacientes con HCC presentan estas características y en el 40% de los casos las presentaciones atípicas plantean un reto diagnóstico y de manejo de los pacientes.

Abstract The typical imaging appearance of hepatocellular carcinoma (HCC) is widely recognized and consists in hyper enhancement in the arterial phase with lavage in the portal and late venous phases, as on computed tomography (CT) as on magnetic resonance imaging (MRI). This pattern is observed in 60% of cases and has been incorporated into the diagnostics directives of the different organizations which participates in the hepatic diseases studies and its presence avoid the necessity of a biopsy. Besides, are auxiliar signs useful on the HCC diagnostic, T2 hyperintensity, presence of grease, venous tumor thrombosis and the growth between intervals in follow up studies. However, not all HCC patients harbor these characteristics and in 40% of cases the atypical introduction proposes a diagnostic and handling challenge of patients.

Mesohepatectomía, una alternativa para el manejo del hepatocarcinoma en paciente no cirrótico: serie de casos / Mesohepatectomy, an alternative for the management of hepatocellular carcinoma in non-cirrhotic patient: case series

Introducción. La resección quirúrgica es el tratamiento de elección de las neoplasias primarias y secundarias del hígado. Los pacientes con hepatocarcinoma de los segmentos centrales representan un reto, siendo la hepatectomía extendida la técnica más usada, sin embargo, el riesgo postquirúrgico de falla hepática es alto, dado que la resección puede comprometer entre el 65 % y el 80 % del volumen hepático. La mesohepatectomía es una alternativa que permite dejar un volumen hepático residual suficiente. El objetivo de este trabajo es presentar nuestra experiencia en el tratamiento de pacientes con hepatocarcinomas en segmentos centrales a quienes se les realizó mesohepatectomía. Serie de casos. Se presentan tres pacientes no cirróticos, con hepatocarcinoma en los segmentos 4, 5 y 8, que fueron atendidos en el Hospital San Vicente Fundación, en las sedes de Medellín y de Rionegro, entre 2018 y 2020. Resultados. La mesohepatectomía se realizó mediante ligadura selectiva de los pedículos del segmento 4 y del sector anterior derecho. Se utilizó aspirador ultrasónico y endograpadora para la transección hepática. La duración de la maniobra de Pringle varió entre 16 y 43 minutos. El sangrado promedio fue de 1000 ml. Solo un paciente presentó fuga biliar tipo B. No hubo mortalidad a 30 días. Conclusiones. La mesohepatectomía es una alternativa segura para pacientes con tumores en los segmentos centrales, que permite disminuir el riesgo de falla hepática luego de la resección.

Introduction. Surgical resection is the treatment of choice for primary and secondary neoplasms of the liver. Patients with central segment hepatocarcinoma represent a challenge, with extended hepatectomy being the most widely used technique. However, the postsurgical risk of liver failure is high since resection can compromise between 65% and 80% of liver volume. Mesohepatectomy is an alternative that allows a sufficient residual liver volume to be left. The objective of this work is to present treatment of patients with central segment hepatocarcinoma.Clinical cases. Three non-cirrhotic patients are presented, with hepatocarcinoma in segments 4, 5 and 8, who were treated at the San Vicente Fundación Hospital in Medellín and Rionegro, between 2018 and 2020.Results. Mesohepatectomy was performed by selective ligation of the pedicles of segment 4 and the right anterior sector. An ultrasonic aspirator and endostapler were used for liver transection. The duration of the Pringle ma-neuver ranged from 16 to 43 minutes. The average bleeding was 1000 cc. Only one patient had type B bile leakage. There was no 30-day mortality.Conclusions. Mesohepatectomy is a safe alternative for patients with tumors in the central segments, which reduces the risk of liver failure after resection.

Hepatocarcinoma: diagnóstico y resección con radiofrecuencia quirúrgica / HEPATOCARCINOMA: DIAGNOSIS AND RESECTION WITH SURGICAL RADIO FREQUENCY

Objetivo: Presentar metodología diagnostica y resección atípica, con fines curativos de hepatocarcinoma. Caso clínico: Femenina de 82 años, con múltiples antecedentes entre el que se destaca, hepatitis a virus C de 15 años de evolución, que presenta por estudios complementarios alta sospecha de hepatocarcinoma, se realiza laparotomía exploradora con resección atípica de tumor en segmento 5 y 6 con radiofrecuencia quirúrgica y colecistectomía con colangiografía intraoperatoria. Cursa post operatorio sin complicaciones con alta sanatorial al 8vo dia. Conclusion: Hay que sospechar esta patología en pacientes con antecedentes de hepatopatía viral, plantear screening adecuado para un diagnóstico temprano y la mejor resolución adaptada a cada paciente. Dentro de las opciones terapéuticas encontramos la radiofrecuencia quirúrgica como una buena herramienta, con índice bajo de complicaciones

Objective: To present diagnostic methodology and atypical resection, for curative purposes of hepatocarcinoma. Clinical case: An 82-year-old female, with multiple history factors, among them, hepatitis C virus of 15 years of evolution, which presents high suspicion of hepatocarcinoma due to complementary studies, exploratory laparotomy is performed with atypical resection of tumor in segments 5 and 6 with surgical radiofrequency and cholecystectomy with intraoperative cholangiography. Post-operative course without complications with sanatorial discharge on the 8th day. Conclusion: This pathology must be suspected in patients with history of viral liver disease. We suggest an adequate screening for an early diagnosis and the best resolution adapted to each patient. Among the therapeutic options we find surgical radiofrequency as a good tool, with a low rate of complications

TGF-ß1 mediates cell proliferation and development of hepatocarcinogenesis by downregulating deiodinase 1 expression / La desregularización de la deiodinasa 1, mediada por TGF-b1, impulsa la proliferación celular y el desarrollo de hepatogénesis

Abstract Hepatocellular carcinoma (HCC) is the most common primary liver tumor. Hexachlorobenzene (HCB) is an endocrine disruptor and a liver tumor promoter. Deregulation of thyroid hormone (TH) homeostasis may play a significant role in early neoplastic transformation. The aim of this study was to evaluate the relation between TH metabolism and the regulation of cell growth in an in vivo and in vitro model. We examined the role of transforming growth factor-β1 (TGF-β1) on TH deiodinase expression and hepatocyte proliferation. An initiation (DEN)/promotion (HCB) tumor model from rat liver and HepG2 cells were used. We evaluated PCNA, p21, p27, SMAD2/3, TGF-β1, deiodinase 1 (D1), D3, protein expression levels; D1 and D3 mRNA expression; TH and TGF-β1, D1, D3, and GST-P protein levels in focal/non-focal areas. In vivo, HCB decreased triiodothyronine (T3) and D1 mRNA levels and increased thyroxine (T4) and D3 mRNA levels in liver from DEN+HCB vs. DEN group. HCB increased protein levels from D3, TGF-β1, and PCNA and decreased D1 in focal-areas. In vitro, HCB increased PCNA, pSMAD 2/3, and TGF-β1 protein levels and mRNA expression and decreased p21 and p27 protein levels. Exogenous T3 treatment prevent HCB induced molecular alterations related to hepatocyte proliferation whereas T4 did not have any effect. These effects were prevented by using a TGF-β1 receptor II inhibitor. Results suggest that alteration of TH homeostasis, through D1 function, play a key role in hepatocyte proliferation and that TGF-β1-SMAD pathway is involved in this process confirming their role in early neoplastic transformation in HCC.

Resumen El hepatocarcinoma (HCC) es un tumor hepático primario. El hexaclorobenceno (HCB) es un disruptor endocrino y un promotor de tumores hepáticos. La desregulación de la homeostasis de las hormonas tiroideas (HT) puede ser un proceso importante para la transformación neoplásica temprana. Nuestro objetivo fue evaluar la relación entre el metabolismo de las HT y la regulación de la prolifera ción celular. Se utilizó un modelo tumoral de iniciación (DEN)/promoción (HCB) de hígado de rata (in vivo) (DEN/ HCB) y células HepG2 (in vitro). Evaluamos los niveles de PCNA, p21, p27, SMAD2/3, TGF-β1, D1, D3, ARNm de D1 y D3, HT y los niveles de TGF-β1, D1, D3 y GST-P en áreas focales/no focales. In vivo, HCB disminuyó los niveles de T3 y ARNm de la D1 y aumentó los niveles de T4 y ARNm de D3 del grupo DEN + HCB frente al grupo DEN. El HCB aumentó los niveles de D3, TGF-β1 y PCNA y disminuyó el D1 en las áreas focales. In vitro, HCB aumentó los niveles de PCNA, pSMAD 2/3 y TGF-β1 y la expresión de ARNm mientras que disminuyó los niveles de p21 y p27. El tratamiento con T3 exógeno previno las alteraciones moleculares relacionadas con la proliferación hepatocitaria. Estos efectos se evitaron utilizando un inhibidor del receptor II de TGF-β1. Los resultados sugieren que la alteración de la homeostasis de HT, a través de la D1 y la vía TGF-β1-SMAD, juega un papel clave en la proliferación celular y en las transformaciones neoplásicas tempranas en el HCC.

Tumor hepático de presentación atípica en imágenes / Liver tumor of atypical presentation in images

RESUMEN El presente manuscrito desea recalcar la importancia de los diferentes métodos de diagnóstico. En este caso el paciente presentó clíni-ca de dolor abdominal y el estudio de ecografía indicó la presencia de una masa; sin embargo, se puede apreciar la disyuntiva que se presenta entre los resultados histopatológicos de la biopsia core, los marcadores serológicos, los estudios de imagen y el diagnóstico definitivo posterior a la resección quirúrgica total de la lesión. El hepatocarcinoma tiene un aspecto tomográfico diferente y presenta elevación de marcadores oncológicos en pacientes con antecedentes previos de hepatopatía, por lo que la presentación de esta forma resulta atípica. Palabras claves: Hepatocarcinoma, cirrosis, metástasis

ABSTRACT This manuscript highlights the importance of the different diagnostic methods. In this case, the patient presented clinical symptoms of abdominal pain and the ultrasound showed the presence of a mass in the liver; however, the diagnosis was not easily achieved because there was a disjunctive between the histopathological result of the core biopsy, the serological markers, and the imaging studies. Definitive diagnosis was only possible after total surgical resection of the lesion. Hepatocellular carcinoma has a different tomographic appearance and presents elevated oncological markers in patients with a previous history of liver disease, so the presentation of this form is atypical.Keywords: Hepatocarcinoma, cirrhosis, metastasis.Correspondencia: Elizabeth ZamoraTeléfonos: 0982546676 e-mail: ezamora@hmetro.med.ecElizabeth Zamora: https://orcid.org/0000-0003-1807-625XFrans Serpa:https://orcid.org/0000-0001-6437-1140Fernanda Avalos:https://orcid.org/0000-0003-1917-3780IDs Orcid

Preliminary Study on Effects of Solamargine on the Growth and Apoptosis of Human Hepatocarcinoma Cells HepG 2 and Its Mechanism / 中国药房

OBJECTIVE：To ex plore the effects of solamargine on the growth and apoptosis of human hepatocarcinoma cells HepG2 and its underlying mechanism. METHODS ：The effects of 0（blank group ）-12 μmol/L solamargine treatment of 24，48 h on survival rate of HepG 2 cells were investigated. The effects of 0（blank group ），6 μmol/L solamargine treatment of 10 days on cell clone formation were also investigated. The effects of 0（blank group ），4，6，8 μmol/L solamargine for 24 h on the apoptotic rate of cells，mRNA expression of Bcl- 2，Bax and caspase- 3， protein expression of Bcl- 2 and cleaved caspase- 3 as well as ratio of p-AMPKα to AMPKα were all tested. The effects of AMPK inhibitor as compound C on the protein expression of AMPKα and Bcl- 2 in cells were investigated after treated with 6 μmol/L solamargine for 24 h. RESULTS ：Compared with 020-39318678。E-mail：wujingjing6028@gzucm.edu.cn blank group ，1-12 μ mol/L solamargine for 24，48 h could significantly decrease the survival rates of cells （P＜0.05）in a concentration-dependent manner ；IC50 of them were 8.310 and 7.996 μmol/L，respectively；the rate of cell clone formation was decreased significantly after treated with 6 μmol/L solamargine for 10 days（P＜0.05）. The apoptotic rate of HepG 2 cells，mRNA expression of Bax and caspase- 3，protein expression of cleaved caspase-3（except for 8 μmol/L）as well as ratio of p-AMPKα to AMPKα（except for 8 μmol/L）were all increased significantly after treated with 6，8 μmol/L solamargine（P＜0.05）；mRNA and protein expression of Bcl- 2 were decreased significantly （P＜ 0.05）；the changes of some indexes were in a concentration-dependent manner. The compound C could inhibit protein expression of AMPKα，and reverse the inhibitory effect of solamargine on Bcl- 2 protein. CONCLUSIONS ：Solamargine can inhibit the proliferation of HepG 2 cells and induce apoptosis ，the mechanism of which may be associated with activating AMPK signaling pathway.

Impacto de la pandemia por COVID-19 sobre el trasplante hepático en la argentina. Otro daño colateral / Impact of COVID-19 pandemic in liver transplantation in Argentina. Other collateral damage

Resumen La pandemia COVID-19 declarada en marzo del 2020, ha generado preocupación mundial por su efecto en la salud de la población y el potencial colapso sanitario. La estrategia de "aplanar la curva" mediante el distanciamiento social permitió adaptar los recursos del sistema de salud a pacientes con COVID-19, pero no se pudo prever su repercusión en otras áreas de la salud. El objetivo de este trabajo fue analizar las consecuencias de la pandemia sobre el trasplante hepático en general y por hepatocarcinoma (HCC). Fueron realizados los siguientes estudios: a) un análisis retrospectivo utilizando datos del CRESI/INCUCAI para comparar ingreso en lista de espera, mortalidad en lista, donación y trasplante hepático desde 20/03 a 15/08, 2019 e igual periodo de 2020, y b) una encuesta a los centros de trasplante de mayor actividad trasplantológica para valorar el efecto de las medidas tomadas en diferentes situaciones institucionales y regionales. El primer análisis evidenció una disminución del 55% de los trasplantes hepáticos, con una reducción similar en la donación y en el ingreso a lista de espera hepática; mientras que el trasplante por HCC ascendió de 10% en 2019 a 22% en 2020. El segundo análisis, mostró que la tasa de ocupación de camas por pacientes COVID-19/semana fue variable: de 0.4% al 42.0%. El número de cirugías, hepato-bilio-pancreática, resección de HCC y trasplante hepático, se redujeron en 47%, 49%, 31% y 36% respectivamente. La reducción de la actividad trasplantológica afectó mayormente los centros con alta ocupación por COVID-19. El impacto final a largo plazo deberá evaluarse.

Abstract The COVID-19 pandemic declared in March 2020, has generated worldwide concern due to its effect on the health of the population and the potential health collapse. The strategy of "flattening the curve" through social distancing made it possible to adapt the resources of the health system to patients with COVID-19, but results in other areas of health could not be predicted. The objective of this work was to analyze the consequences of the pandemic on liver transplantation in general and for hepatocarcinoma (HCC). The following studies were carried out: a) a retrospective analysis using data from the CRESI / INCUCAI to compare admission to the waiting list, mortality on the list, donation and liver transplantation from 03/20 to 08/15, 2019 and the same period in 2020, and b) a survey of the transplant centers with the highest transplant activity to assess the effect of the measures taken in different institutional and regional situations. The first analysis showed a 55% decrease in liver transplants, with a similar reduction in donation and admission to the liver waiting list; while HCC transplantation rose from 10% in 2019 to 22% in 2020. The second analysis showed that the occupancy rate of beds by COVID-19 patients / week was variable: from 0.4% to 42.0%. The number of surgeries, hepato-bilio-pancreatic, resection of HCC and liver transplantation, were reduced by 47%, 49%, 31% and 36% respectively. The reduction in transplant activity mainly affected centers with high occupancy due to COVID-19. The final long-term outcome will need to be assessed.

Tromboembolismo tumoral como causa directa de muerte / Tumor thromboembolism as direct cause of death

Introducción: el embolismo tumoral pulmonar es la presencia de acúmulos de células tumorales en las arterias pulmonares arteriolas y capilares pulmonares. Su incidencia en autopsias ha sido descrita entre 3 y 26 por ciento de los pacientes con tumores sólidos, más frecuentemente de mama, estómago, hígado y pulmón. Objetivo: describir los argumentos clínicos que sugieren la sospecha diagnóstica de tromboembolismo tumoral en una paciente atendida en el Hospital Dr. Carlos J Finlay de La Habana, Cuba. Presentación del caso: paciente femenina de 80 años de edad con antecedentes patológicos personales de cirrosis hepática por virus de hepatitis C. Dos meses antes del ingreso comienza con síntomas generales asociados a edemas en miembros inferiores y diarreas. Ingresa en un servicio de Medicina Interna con el diagnóstico de cirrosis hepática descompensada y la sospecha de hepatocarcinoma. Al quinto día de su ingreso comienza de forma súbita con disnea y fallece. Conclusiones: los hallazgos anatomopatológicos informan como causa directa de muerte tromboembolismo tumoral. La embolia pulmonar tumoral debe ser considerada como diagnóstico diferencial en todo paciente con evidencia de neoplasia que presente disnea(AU)

Introduction: Pulmonary tumor thromboembolism is the presence of accumulations of tumor cells in the pulmonary arterioles and pulmonary capillaries. Its incidence in autopsies has been described between 3 percent and 26 percent of patients with solid tumors, most frequently in breast, stomach, liver and lung tumors. Objective: To describe clinical arguments suggesting the suspected diagnosis of tumor thromboembolism in a patient treated at the "Dr. Carlos J. Finlay'' Hospital in Havana, Cuba. Case presentation: Eighty-year-old female patient with personal pathological antecedents of liver cirrhosis due to hepatitis C virus. Two months before admission she started presenting general symptoms associated with edemaof the lower limbs and diarrhea. She was admitted to an Internal Medicine service with the diagnosis of decompensated hepatic cirrhosis and the suspicion of hepatocarcinoma. On the fifth day after admission, he suddenly began with dyspnea and died. Conclusions: Anatomopathological findings report tumor thromboembolism as a direct cause of death. Pulmonary tumor thromboembolism should be considered in the differential diagnosis of all patients with evidence of neoplasia who are presenting dyspnea(AU)

Comparison of Anti-hepatocarcinoma Effect of Curcumin and Hydrazincurcumin and Mechanism Study / 中国药房

OBJECTIVE：To compare the an ti-hepatocarcinoma effects of curcumin （CUR）and its derivative hydrazincurcumin （HZC），and to explore the mechanism. METHODS ：MTT assay was used to detect the effects of CUR or HZC （2.5，5，10，20， 40，80 μmol/L）on the proliferation of HepG 2 cells. Flow cytometry was used to detect the effects of CUR or HZC （10，20，40 μmol/L）on cell cycle distribution and apoptosis of HepG 2 cells. Western blotting assay was used to detect the effects of CUR or HZC（10，20，40 μmol/L）on the expression of apoptosis-related protein in HepG 2 cells. The male SD rats were randomly divided into normal control group （n＝10），CUR control group （n＝10），HZC control group （n＝10），model group （n＝30），CUR protection group （n＝30）and HZC protection group （n＝30）. CUR control group and HZC control group were given CUR 85917439。E-mail：zhaoji-an-88@163.com or HZC （80 mg/kg） intraperitoneally. Model group ，CUR protection group and HZC protection group were given diethylnitrosamine （50 mg/kg）intraperitoneally to establish hepatocarcinoma model ；at the same time ，2 protection groups were given CUR or HZC （80 mg/kg）intraperitoneally，twice a day，for consecutive 12 weeks. During medication ，the change of body weight and death of rats were recorded. Twenty four weeks later，liver index of rats was calculated and appearance was observed ；the number of cancer nodules was counted ；HE staining was used to observe the pathological changes of liver tissue and calculate the nuclear division index of hepatocarcinoma ；the proliferating cell nuclear antigen （PCNA）index was detected by immunohistochemistry. RESULTS ：CUR and HZC could increase the inhibitory rate of HepG 2 cells（P＜0.05），and increased the percentage at G 0/G1 phase and apoptotic rate of HepG 2 cells（P＜ 0.05）. CUR and HZC could significantly decrease the protein expression of p-JAK 2，p-STAT3，Bcl-2 and Bcl-xl ，while increased the protein expression of Bax ，Cyt-c，Caspase-9，Caspase-3 and PAPR （P＜0.05）. Above effects of HZC were significantly better than those of CUR （P＜0.05）. The results of animal experiment showed that there was no death ，no liver canceration and no pathological changes in liver appearance and tissue section of the three control groups ；there was no statistical significance in body weight and its increased weight ，liver index ，nuclear division index of carcinoma or PCNA index （P＞0.05）. Compared with model group， survival rate of rats were increased significantly in CUR protection group and HZC protection group ， while hepatocarcinoma incidence and the number of cancer nodules were decreased significantly （P＜0.05）；body weight and its increased weight were increased significantly ，while liver index ，nuclear division index of carcinoma and PCNA index were decreased significantly （P＜0.05）. There were some pathological changes in liver appearance and tissue section ；cancerous lesions with focal necrosis or cancerous lesions with patchy necrosis were observed. There was no statistical significance in the improvement of above indexes in 2 protection groups （P＞0.05）. CONCLUSIONS ：HZC could inhibit the proliferation and induce apoptosis of HepG 2 cells by inhibiting JAK 2/STAT3 signaling pathway and regulating the activation of mitochondrial endogenous pathway，which shows stronger anti-hepatocarcinoma effect in vitro than CUR. On the other hand ，there was no significant difference in the improvement of liver caner indexes in hepatic cancer model rats between HZC and CUR.

Hepatocarcinoma fibrolamelar. Presentación de un caso clínico / Fibrolamellar hepatocarcinoma. Presentation of a clinical case / Hepatocarcinoma fibrolamelar. Relato de um caso clínico

Resumen: El hepatocarcinoma fibrolamelar es una entidad poco frecuente cuya incidencia varía entre 1% y 5% en el porcentaje de todos los hepatocarcinomas. Afecta principalmente a pacientes jóvenes con hígado sano, y en el 50% de los casos su diagnóstico se realiza en etapas avanzadas de la enfermedad. Se presenta el caso de un paciente de 15 años de edad, sano, que consulta por tumoración abdominal de tres meses de evolución, dolor en epigastrio y adelgazamiento. Los estudios de imagen informan tumoración que sustituye el lóbulo izquierdo del hígado con realce heterogéneo en la fase arterial, que infiltra la vena suprahepática izquierda. Además, informa lesiones en los segmentos V y VIII, extensas adenopatías en el hilio hepático, y nódulos a nivel peritoneal y subpleural. Se realizó punción biópsica hepática que confirmó el diagnóstico de hepatocarcinoma fibrolamelar, iniciándose tratamiento oncoespecífico.

Summary: Fibrolamellar hepatocellular carcinoma is a rare entity that represent between 1% to 5% of all hepatocarcinomas. Tipically affects younger patients (10 to 30 year of age) of both sexes, without underlying liver disease. In 50% of the cases the diagnosis is made in advanced stages of the disease. We present the case of a male patient of 15 years of age, healthy, who consulted due to an abdominal tumor of 3 months evolution, epigastric pain and weight loss. The imaging studies report a tumor that replaces the left lobe with heterogeneous enhancement in the arterial phase that infiltrates the left suprahepatic vein. Injuries in segment V and VIII. Extensive lymphadenopathy in the liver liver. Peritoneal and subpleural nodule. Hepatic biopsy puncture was performed confirming fibrolaminar hepatocarcinoma. Start once specific treatment.

Resumo: Entidade pouco frequente cuja incidência varia entre 1% e 5% de todos os hepatocarcinomas. Acomete principalmente pacientes jovens com fígado saudável e em quase 50% dos casos o diagnóstico é feito em estágios avançados da doença. Apresentamos o caso de um paciente do sexo masculino, de 15 anos de idade, saudável, que consultou devido a um tumor abdominal de 3 meses de evolução, dor epigástrica e perda de peso. Os estudos de imagem relatam um tumor que substitui o lobo esquerdo com realce heterogêneo na fase arterial que infiltra a veia supra-hepática esquerda. Lesões do segmento V e VIII. Linfadenopatia extensa no fígado do fígado. Nódulo peritoneal e subpleural. A punção da biópsia hepática foi realizada confirmando o hepatocarcinoma fibrolaminar. Iniciar um tratamento específico.

Hepatocarcinoma en hígado no cirrótico: serie bicéntrica de 19 casos / Hepatocellular carcinoma in the non-cirrhotic liver: a two-center experience with 19 cases

Antecedentes: El carcinoma hepatocelular es la neoplasia hepática más frecuente; el 90% se desarrolla sobre hígado cirrótico o con hepatopatía crónica, constituyendo así el principal factor de riesgo; la inflamación crónica, la necrosis y regeneración que estas producen condiciona la aparición de mutaciones genéticas y el desarrollo de células tumorales. Sin embargo, el 10% se desarrolla sobre hígado sano, no cirrótico y sin factores desencadenantes. Material y métodos: Se realizó un análisis descriptivo y de la supervivencia de una serie de 19 pacientes con anatomía patológica de carcinoma hepatocelular y ausencia de antecedentes de cirrosis hepática o hepatopatía crónica intervenidos en dos Unidades HPB en el período enero 2007- enero 2016. Resultados: La serie incluyó 13 varones y 6 mujeres con una edad media de 65 años. La presentación clínica más frecuente fue dolor abdominal. El 60% registraba analítica normal y solo en el 16% se elevó la AFP. El 61% presentó prueba de imagen diagnóstica. El tamaño medio fue de 110,6 mm. A todos se los trató con cirugía. Ocurrieron complicaciones en el 36,8% de los pacientes y una supervivencia a los 5 años del 62,3%. Conclusión: el carcinoma hepatocelular suele diagnosticarse cuando es de gran tamaño por hallazgos en pruebas de imagen realizadas generalmente en el estudio del dolor abdominal. La cirugía ofrece tratamiento curativo, pudiendo realizarse grandes resecciones con un alto índice de seguridad, con morbimortalidad perioperatoria baja y con bajo índice de insuficiencia hepática, ya que el remanente hepático es sano y la función hepática se mantiene.

Background: Hepatocellular carcinoma is the most common type of primary liver cancer and is the third cause of cancer related deaths; 80% of the HCC are associated with cirrhotic livers or chronic liver diseases, which constitute the main risk factor. Chronic inflammation, necrosis and regeneration due to these conditions produce genetic mutation and development of tumor cells. Yet, 10% develop in non-cirrhotic healthy livers without precipitating factors. Material and methods: We conducted a retrospective analysis of the characteristics and survival of patients with diagnosis of hepatocellular carcinoma in non-cirrhotic liver and absence of a history of liver cirrhosis or chronic liver disease undergoing surgery in two hepato-pancreato-biliary units between January 2007 and January 2016. Results: Mean age was 65 years and 13 patients were men. Abdominal pain was the most common clinical presentation. Liver panel was normal in 60% of the cases and alpha-fetoprotein was elevated in only 16%. The diagnosis was made by imaging tests in 61% of the cases. Mean tumor size was 110.6 cm. All the patients underwent surgery. Complications were observed in 36.8% of the patients and survival at 5 years was 62.3%. Conclusion: hepatocellular carcinoma is usually diagnosed as a large lesion in imaging tests ordered due to abdominal pain. Surgery provides curative treatment, and large resections can be safely performed, with low perioperative morbidity and mortality and low incidence of postoperative liver failure, since the liver remnant is healthy and liver function is maintained.

Caesalpinia bonduc Linn Extracts Exhibit Hepatoprotective Effect on HepG2 Cells against Paracetamol by Up-regulating Glutathione Related Genes

Background: Caesalpinia bonduc (CB) is said to ownvarious pharmacological and therapeutic applicationagainst a number of diseases. It is used widely in folkmedicine to treat liver diseases. In the present study,we have made a sincere effort to evaluate thehepatoprotective activity of CB leaf extracts againstParacetamol (PCM) induced toxicity and theirmechanism of hepatoprotection in the humanHepatocarcinoma cells (HepG2 cells) therebyproviding scientific evidence for the same. Materialand Methods:The hepatoprotective activity of CB wasassessed in-vitro by the estimation of glutathione(GSH) and Malondialdehyde (MDA), anti-apoptoticassay/Annexin V and the expressions of genes such asGlutathione Reductase (GS-R) and GlutamateCysteine Ligase, Catalytic (GCLC). Results: Theobtained results suggest that the aqueous extract of CBpossess significant hepatoprotective activity. Thisactivity may be due to the possible antioxidantproperty and the free radical scavenging ability of theextracts, which might clear the toxic metabolites ofPCM. Conclusion: The present study suggests that theaqueous extract of CB have potential hepatoprotectiveactivity, which may prevent the lipid peroxidation ofthe cell membrane by its antioxidant properties.

Decellularized matrix of human fatty liver used for three-dimensional culture of hepatocellular carcinoma cells / 南方医科大学学报

OBJECTIVE@#To construct a decellularized matrix of human fatty liver as the scaffold for three-dimensional (3D) culture of hepatocarcinoma cells.@*METHODS@#Human fatty liver decellularized matrix (hFLM) was prepared by repeated freezingthawing, perfusion with gradient SDS and 1% Triton X-100 through the portal vein and hepatic artery, and repeated agitation with Triton X-100. HepG2 cells were cultured in the prepared hFLM, and the cell survival, morphology, proliferation and cellular expressions of the adhesion molecules were detected.@*RESULTS@#The decellularization procedure shortened the time for scaffold preparation and preserved the 3D ultrastructure and the composition of the extracellular matrix. HepG2 cells cultured in hFLM scaffold maintained proliferation for up to 15 days and showed a growth pattern with a long lag phase and a slow growth rate, which was similar to the growth pattern . The cultured HepG2 exhibited a low expression of E-cadherin and a high expression of vimentin, which was consistent with the xenograft but opposite to 2D cultured cells. However, the lack of adequate nutrient transport in this hepatocarcinoma cell model led to a slowdown of cell proliferation in the later stage. The PCNA index of HepG2 cells cultured in hFLM was lowered by 29.3% on day 12 as compared with that on day 6.@*CONCLUSIONS@#We established a new protocol for preparing hFLM and confirmed the feasibility of constructing hepatocarcinoma cell models using the hFLM scaffold.

Glaucocalyxin A regulates STAT3 signaling pathway through influencing IL-6 expression in HCCLM3 cells / 中华微生物学和免疫学杂志

Objective To investigate the effects of glaucocalyxin A ( GLA) on the expression of signal transduction and activator of transcription 3 (STAT3) signaling pathway in HCCLM3 cells for better understand-ing the role of GLA in tumor metastasis. Methods HCCLM3 cells were stimulated by different concentrations (0. 1 ng/ml, 1 ng/ml, 10 ng/ml, 100 ng/ml and 1000 ng/ml) of GLA for 48 h. Expression of IL-6, STAT3/pSTAT3Tyr705 and MMP9 at mRNA and protein levels were detected by qRT-PCR and Western blot, respectively. Transwell invasion and migration assays were performed to analyze cell invasion and migration. ELISA was used to measure the concentrations of IL-6 in culture media. Results Expression of IL-6 at mRNA and protein lev-els, STAT3Tyr705 phosphorylation, and the migration and invasion of HCCLM3 cells were significantly enhanced after stimulation of HCCLM3 cells with 0. 1 ng/ml of GLA, but inhibited by GLA at the concentration of 1000 ng/ml. Moreover, more IL-6 was secreted out of the HCCLM3 cells treated with 0. 1 ng/ml of GLA. Conclu-sions GLA might affect the metastasis of HCCLM3 cells through regulating the expression of IL-6 and the phos-phorylation of STAT3Tyr705. These regulatory effects were closely related to the concentration of GLA.

Effect of Modified Lichongtang Combined with 5-Fluorouracil on Epithelial Mesenchymal Transition in H22 Tumor-bearing Mice / 中国实验方剂学杂志

Objective: To investigate the effect of modified Lichongtang combined with 5-fluorouracil (5-FU) on tumor epithelial-mesenchymal transition (EMT) in H22 tumor-bearing mice. Method: Mouse models of transplanted hepatoma were constructed. After tumor formation, they were randomly divided into 4 groups:blank group, 5-FU group(2.5 mg·kg-1 5-FU intraperitoneal injection), modified Lichongtang combined with 5-FU group (5-FU+Chinese medicine group), and modified Lichongtang group (Chinese medicine group,25 g·kg-1 gavage),n=10 in each group. The effect of modified Lichongtang combined with 5-FU on the tumor inhibition rate of subcutaneous transplanted tumor was observed. The gene expression levels of E-cadherin,N-cadherin,Snail,and Twist in transplanted tumor were observed by Real-time PCR. The protein expression levels of E-cadherin,N-cadherin,Snail,and Vimentin were detected by using Western blot. Result: The tumor inhibiting rate was 59.18%,84.42%,and 10.39% respectively in 5-FU group, 5-FU+Chinese medicine group,and Chinese medicine group. All of these can inhibit the growth of liver cancer transplantation tumor, and the tumor inhibiting rate of 5-FU+Chinese medicine group was significantly higher than that in 5-FU group (PPPPPPPPPPPConclusion: Modified Lichongtang, 5-FU and their combination have inhibitory effect on the growth of transplanted tumors of hepatocarcinoma mice, and the combination of the two drugs can enhance the effect of chemotherapy and to some extent inhibit the toxicity of 5-FU. The mechanism may be related to the inhibition of liver cancer EMT.

Mechanism of Liuwei Dihuangwan in Enhancing Hepatocarcinoma Suicide Gene Therapy from Cx32 / 中国实验方剂学杂志

Objective: To investigate the effect of Liuwei Dihuangwan on connexin 32 (Cx32) in hepatoma cell line CBRH7919 and its gap junction intercellular communication (GJIC), and furthermore study its mechanism of enhancing the bystander killing effect of suicide gene therapy. Method: Liuwei Dihuangwan (32 g·kg·d-1) and the same volume of normal saline were given to the rats by intragastrical administration. Blood was taken to prepare the medicated serum of Liuwei Dihuangwan and blank control serum, respectively. The hepatoma cell line CBRH7919 were treated by control serum and medicated serum of Liuwei Dihuangwan in different concentrations. There were four groups in experiment:the blank control group (volume fraction of 10%), medicated serum high dose group of Liuwei Dihuangwan (the volume fraction of 10%), medicated serum middle dose group of Liuwei Dihuangwan (the volume fraction of 5%), and medicated serum low dose group of Liuwei Dihuangwan (the volume fraction of 2.5%). The expression levels of Cx32 protein and mRNA in hepatoma cell line CBRH7919 were detected by indirect immunofluorescence assay (ⅡA) and Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) assay. The fluorescence redistribution after photobleaching (FRAP) method was used to detect the function of GJIC of hepatoma cell line CBRH7919. Result: ① The indirect immunofluorescence assay (ⅡA) analysis indicated that as compared with the blank control group, the cx32 expression of CBRH7919 cells was up-regulated in a concentration-dependent manner in each dose group of the serum containing Liuwei Dihuangwan (PPPPConclusion: The mechanism of medicated serum of Liuwei Dihuangwan in enhancing the bystander killing effect of suicide geneis related to gap junction. Liuwei Dihuangwan may enhance the function of GJIC by increasing the localization of cx32 on the cell membrane of CBRH7919 cells and increasing the expression of cx32 mRNA and protein to achieve the synergistic action.

Revisión del hepatocarcinoma fibrolamelar / Fibrolamellar Hepatocelullar Carcinoma

El carcinoma hepatocelular fibrolamelar (CHC-FL) es una variante poco frecuente de CHC convencional, representa el 0,85 al 16% de todos los carcinomas hepatocelulares. Se presenta en personas jóvenes, sin antecedente de enfermedad hepática crónica subyacente, alrededor del 65-85% de estos tumores ocurren en pacientes menores de 40 años. Para su diagnóstico, las modalidades de imagen cumplen un papel importante tanto el ultrasonido, tomografía y resonancia magnética principalmente ésta última podría aportar sustancialmente al diagnóstico. Se presenta el caso de un joven de 16 años con diagnóstico histopatológico de hepatocarcinoma fibrolamelar y su correlación con las diferentes modalidades de imagen, el cual fue sometido a trasplante hepático, se realiza la revisión del mismo dada la importancia del diagnóstico por imagen y las alternativas terapéuticas en estos casos.

Fibrolamellar hepatocellular carcinoma (CHC-FL) is a rare variant of conventional HCC, representing 0.85 to 16% of all hepatocellular carcinomas. It occurs in young people, without a history of underlying chronic liver disease, about 65-85% of these tumors occur in patients under 40 years. For its diagnosis, imaging modalities play an important role, both ultrasound, tomography and magnetic resonance, mainly the latter could contribute substantially to the diagnosis. We present the case of a 16-year-old boy with a histopathological diagnosis of fibrolamellar hepatocellular carcinoma and its correlation with the different imaging modalities, which underwent hepatic transplantation. He was reviewed, given the importance of imaging diagnosis and alternatives. therapeutic in these cases.

Hepatitis C: una aproximación clínica y epidemiológica en Cali, Colombia / Clinical and epidemiological approach to Hepatitis C in Cali, Colombia

Resumen Introducción: en Colombia, la infección por el virus de la hepatitis C (VHC) representa alta morbilidad y elevados costos. Con la llegada de nuevos tratamientos más efectivos, se hace necesario conocer las características propias de esta población para su adecuado uso. Objetivos: describir las características epidemiológicas y clínicas de los pacientes con VHC manejados en un centro de referencia en enfermedades hepáticas. Materiales y métodos: se realizó un estudio descriptivo de corte transversal en una población de adultos con diagnóstico serológico de VHC entre el 2011 y el 2016. Resultados: se evaluaron 214 historias clínicas de pacientes con diagnóstico serológico confirmado de VHC. La mediana de edad fue de 59 años y el 62 % fue de sexo femenino. El genotipo se reportó en 114 pacientes, el 75 % presentó genotipo 1B. El 36,9 % de los pacientes había recibido algún hemoderivado y el 5 % tenía tatuajes. La prevalencia de cirrosis fue del 29,4 % y de hepatocarcinoma fue del 3,3 %. El 1,8 % y el 5,1 % de los pacientes presentó coinfección con el virus de la hepatitis B (VHB) y virus de la inmunodeficiencia humana (VIH), respectivamente. Conclusión: los factores determinantes de la infección por el VHC en Cali presentan un comportamiento clínico similar al que reporta la literatura científica a nivel mundial, lo que obliga a enfatizar en la prevención de la población en riesgo. El genotipo 1B continúa siendo el más frecuente en nuestro medio, lo que hace a esta población susceptible a los nuevos tratamientos.

Abstract Introduction: In Colombia, Hepatitis C virus infections have high rates of morbidity and high costs. The advent of new more effective treatments has produced a need for better knowledge of this population's characteristics to allow their proper use. Objectives: The objective of this study is to describe the epidemiological and clinical characteristics of patients with hepatitis C at a referral center for liver diseases. Materials and methods: We conducted a cross-sectional descriptive study of a population of adults with serological diagnoses of hepatitis C between 2011 and 2016. Results: We evaluated 214 clinical records of patients with confirmed serological diagnoses of hepatitis C. Their median age was 59 years, and 62 % were women. The HCV genotypes of 114 patients were reported: 75 % had genotype 1B. Transfusions of one or another type of blood product had been administered to 36.9 % of the patients, and 5% had tattoos. The prevalence of cirrhosis was 29.4 % while that of hepatocellular carcinoma was 3.3 %. Hepatitis B virus coinfections were found in 1.8 % of these patients, and 5.1 % of the patients had human immunodeficiency virus coinfections. Conclusion: The determinants of hepatitis C virus infection in Cali are similar to those reported in scientific literature worldwide and requires emphasis on prevention in the at-risk population. Genotype 1b continues to be the most frequent in our environment which makes this population susceptible to new treatments.