Presentación inusual de coriocarcinoma metastásico a hígado y pulmón: un reporte de caso / Unusual presentation of metastatic choriocarcinoma to liver and lung: a case report

La enfermedad trofoblástica gestacional (ETG) es un trastorno proliferativo del trofoblasto. Incluye la mola hidatidiforme, el coriocarcinoma, la mola invasiva, el tumor trofoblástico del lecho placentario y el tumor trofoblástico epitelioide. Las últimas cuatro hacen parte de la neoplasia trofoblástica gestacional, que agrupa menos del 1% de todos los tumores ginecológicos. La incidencia de la ETG puede variar, siendo aproximadamente de 1 a 3 de cada 1.000 embarazos en América del Norte y Europa. El coriocarcinoma es la forma más agresiva por su rápida invasión vascular y compromiso metastásico. Sin embargo, es un tumor muy quimiosensible con una alta tasa de respuestas y posibilidad de curación superior al 90%. Se presenta el caso de una paciente de 40 años quien ingresó al servicio de urgencias por disnea súbita secundaria a tromboembolia pulmonar y posteriormente tras el inicio de anticoagulación presentó hemoperitoneo debido a lesiones hepáticas metastásicas de un coriocarcinoma, además de compromiso metastásico pulmonar. Se presenta este caso por ser una patología poco frecuente, agresiva y con presentaciones inusuales, con el fin de mostrar la importancia de un diagnóstico y tratamiento oportuno.

Gestational trophoblastic disease (GTD) is a condition in which the trophoblast, a layer of cells surrounding the embryo, develops abnormally. GTD includes both pre-malignant and malignant pathologies, such as hydatidiform mole, choriocarcinoma, invasive mole, placental site trophoblastic tumor, and epithelioid trophoblastic tumor. Although GTD is rare, it affects about 1 to 3 out of every 1,000 pregnancies in North America and Europe. Choriocarcinoma is the most aggressive form of GTD, as it can quickly invade blood vessels and metastasize to other parts of the body. However, it is highly responsive to chemotherapy, with a cure rate of over 90%. In this case, a 40-year-old patient presented to the emergency department with sudden dyspnea due to pulmonary embolism. After starting anticoagulation therapy, she developed hemoperitoneum due to the spread of choriocarcinoma to her liver, as well as pulmonary metastases. This case is noteworthy because of its unusual presentation and aggressive nature, underscoring the importance of early diagnosis and treatment.

Sclerosing Hemangioma of the Liver. Unusual and Benign Hepatic Neoplasm / Hemangioma Esclerosante del Hígado. Neoplasia Hepática Inusual y Benigna

SUMMARY: Hemangiomas are the most common non-cystic benign liver tumors. Typically, they are incidentally discovered through routine radiological imaging. These tumors can become complicated and develop fibrosis, with the extreme presentation being hepatic sclerosing hemangioma (HSH), a very rare, atypical benign tumor. Initial diagnosis of HSH is often erroneous, as it can be confused with primary or secondary malignant liver neoplasms. Consequently, HSH are frequently resected, and the diagnosis is confirmed through histological and immunohistochemical studies of the resected specimen. The aim of this manuscript was to report a surgically treated case of HSH and review the existing evidence regarding its clinical and morphological characteristics. The case of a 79-year-old male patient, who underwent surgical intervention for HSH at RedSalud Mayor Temuco Clinic in October 2023, was examined. A solid tumor situated Segment VI, measuring 4 cm in its largest dimension was identified. MRI demonstrated a mass with low-signal intensity mass on T1-weighted images and areas of high-signal intensity on T2-weighted images and a hypointense mass in the hepatobiliary phase. The tumor was completely excised. Subsequent to histopathological analysis, immunohistochemical staining was performed for WT1, CD31, ERG, CD34, and Pancitoqueratina AE3 & AE1. The patient experienced an uneventful postoperative course and was discharged on the third day after the surgery. During follow-up assessments, the patient's overall condition remains satisfactory. HSH is an exceedingly rare tumor. Clinical features and imaging findings associated with this type of lesion are non-specific. It should be included in the differential diagnosis of solid liver lesions. Complete surgical resection with clear margins is the treatment of choice, and it prognosis is favorable.

Los hemangiomas son los tumores hepáticos no quísticos benignos más comunes. Lo habitual es que se descubran de forma incidental con imágenes radiológicas de rutina. Estos pueden complicarse y desarrollar fibrosis, cuya presentación extrema es el hemangioma esclerosante hepático (HEH); un tumor benigno atípico muy poco frecuente, cuyo diagnóstico inicial suele ser erróneo, confundiéndose con neoplasias malignas primarias o secundarias del hígado. Por ello, es frecuente que sean resecadas y que el diagnóstico se establezca mediante estudios histológicos y de inmunohistoquímica del espécimen resecado. El objetivo de este manuscrito fue reportar un caso de HEH, que fue intervenido quirúrgicamente; y revisar la evidencia existente respecto de sus características morfológicas y clínicas. Caso clínico: Hombre de 79 años, con HEH intervenido quirúrgicamente en Clínica RedSalud Mayor Temuco en octubre de 2023. Se verificó un tumor sólido de 4 cm de diámetro mayor, localizado en el segmento VI del hígado. La resonancia magnética demostró una masa con baja intensidad de señal en T1 y áreas de alta intensidad de señal en T2. El tumor fue extirpado por completo. Después del estudio histopatológico, se realizaron tinciones inmunohistoquímicas complementarias para WT1, CD31, ERG, CD34 y Pancitoqueratina AE3 & AE1. El paciente tuvo un curso postoperatorio sin incidentes, siendo dado de alta al tercer día postoperatorio. En el control alejado, se encuentra en buenas condiciones generales. El HEH es un tumor muy poco frecuente. Las características clínicas e imágenes de este tipo de lesiones son inespecíficas. Debe de las lesiones sólidas del hígado. La resección considerarse en el diagnóstico diferencial quirúrgica completa con bordes libres es el tratamiento de elección; y su pronóstico es favorable.

Invivo and invitro evaluation of antitumor effects of iron oxide and folate core shell-iron oxide nanoparticles / Avaliação in vivo e in vitro dos efeitos antitumorais de nanopartículas de óxido de ferro e óxido de ferro com núcleo de folato

Abstract Nanoparticles are considered viable options in the treatment of cancer. This study was conducted to investigate the effect of magnetite nanoparticles (MNPs) and magnetite folate core shell (MFCS) on leukemic and hepatocarcinoma cell cultures as well as their effect on the animal model of acute myelocytic leukemia (AML). Through current study nanoparticles were synthesized, characterized by various techniques, and their properties were studied to confirm their nanostructure. Invivo study, nanoparticles were evaluated to inspect their cytotoxic activity against SNU-182 (human hepatocellular carcinoma), K562 (human leukemia), and THLE2 (human normal epithelial liver) cells via MTT test. Apoptotic signaling proteins Bcl-2 and Caspase-3 expression were inspected through RT-PCR method. A cytotoxic effect of MNPs and MFCS was detected in previous cell cultures. Moreover, the apoptosis was identified through significant up-regulation of caspase-3, with Bcl-2 down-regulation. Invitro study, AML was induced in rats by N-methyl-N-nitrosourea followed by oral treatment with MNPS and MFCS. Biochemical indices such as aspartate and alanine amino transferases, and lactate dehydrogenase activities, uric acid, complete blood count, and Beta -2-microglubulin were assessed in serum. Immunophenotyping for CD34 and CD38 detection was performed. Liver, kidney, and bone marrow were microscopically examined. Bcl-2 promoter methylation, and mRNA levels were examined. Although, both MNPs and MFCS depict amelioration in biochemical parameters, MFCS alleviated them toward normal control. Anticancer activity of MNPs and MFCS was approved especially for AML. Whenever, administration of MFCS was more effective than MNPs. The present work is one of few studies used MFCS as anticancer agent.

Resumo Nanopartículas são consideradas opções viáveis ​​no tratamento do câncer. Este estudo foi conduzido para investigar o efeito de nanopartículas de magnetita (MNPs) e núcleo de folato de magnetita (MFCS) em culturas de células leucêmicas e de hepatocarcinoma, bem como seu efeito no modelo animal de leucemia mielocítica aguda (LMA). Através do atual estudo, nanopartículas foram sintetizadas, caracterizadas por várias técnicas, e suas propriedades foram estudadas para confirmar sua nanoestrutura. No estudo in vivo, as nanopartículas foram avaliadas para inspecionar sua atividade citotóxica contra células SNU-182 (carcinoma hepatocelular humano), K562 (leucemia humana) e THLE2 (fígado epitelial humano normal) por meio do teste MTT. A expressão das proteínas sinalizadoras apoptóticas Bcl-2 e Caspase-3 foram inspecionadas através do método RT-PCR. Um efeito citotóxico de MNPs e MFCS foi detectado em culturas de células anteriores. Além disso, a apoptose foi identificada por meio de regulação positiva significativa da Caspase-3, com regulação negativa de Bcl-2. No estudo in vitro, a AML foi induzida em ratos por N-metil-N-nitrosoureia seguida por tratamento oral com MNPS e MFCS. Índices bioquímicos como aspartato e alanina aminotransferases e atividades de lactato desidrogenase, ácido úrico, hemograma completo e Beta-2-microglubulina foram avaliados no soro. A imunofenotipagem para detecção de CD34 e CD38 foi realizada. Fígado, rim e medula óssea foram examinados microscopicamente. A metilação do promotor Bcl-2 e os níveis de mRNA foram examinados. Embora tanto os MNPs quanto os MFCS representem uma melhora nos parâmetros bioquímicos, o MFCS os aliviou em direção ao controle normal. A atividade anticâncer de MNPs e MFCS foi aprovada especialmente para AML. Sempre, a administração de MFCS foi mais eficaz do que MNPs. O presente trabalho é um dos poucos estudos que utilizou o MFCS como agente anticâncer.

Up-regulation of GINS1 highlighted a good diagnostic and prognostic potential of survival in three different subtypes of human cancer / A regulação positiva de GINS1 destacou um bom potencial diagnóstico e prognóstico de sobrevivência em três subtipos diferentes de câncer humano

Abstract Cancer is a fatal malignancy and its increasing worldwide prevalence demands the discovery of more sensitive and reliable molecular biomarkers. To investigate the GINS1 expression level and its prognostic value in distinct human cancers using a series of multi-layered in silico approach may help to establish it as a potential shared diagnostic and prognostic biomarker of different cancer subtypes. The GINS1 mRNA, protein expression, and promoter methylation were analyzed using UALCAN and Human Protein Atlas (HPA), while mRNA expression was further validated via GENT2. The potential prognostic values of GINS1 were evaluated through KM plotter. Then, cBioPortal was utilized to examine the GINS1-related genetic mutations and copy number variations (CNVs), while pathway enrichment analysis was performed using DAVID. Moreover, a correlational analysis between GINS1 expression and CD8+ T immune cells and a the construction of gene-drug interaction network was performed using TIMER, CDT, and Cytoscape. The GINS1 was found down-regulated in a single subtypes of human cancer while commonly up-regulated in 23 different other subtypes. The up-regulation of GINS1 was significantly correlated with the poor overall survival (OS) of Liver Hepatocellular Carcinoma (LIHC), Lung Adenocarcinoma (LUAD), and Kidney renal clear cell carcinoma (KIRC). The GINS1 was also found up-regulated in LIHC, LUAD, and KIRC patients of different clinicopathological features. Pathways enrichment analysis revealed the involvement of GINS1 in two diverse pathways, while few interesting correlations were also documented between GINS1 expression and its promoter methylation level, CD8+ T immune cells level, and CNVs. Moreover, we also predicted few drugs that could be used in the treatment of LIHC, LUAD, and KIRC by regulating the GINS1 expression. The expression profiling of GINS1 in the current study has suggested it a novel shared diagnostic and prognostic biomarker of LIHC, LUAD, and KIRC.

Resumo O câncer é uma doença maligna fatal e sua crescente prevalência mundial exige a descoberta de biomarcadores moleculares mais sensíveis e confiáveis. Investigar o nível de expressão de GINS1 e seu valor prognóstico em cânceres humanos distintos, usando uma série de abordagens in silico em várias camadas, pode ajudar a estabelecê-lo como um potencial biomarcador de diagnóstico e prognóstico compartilhado de diferentes subtipos de câncer. O mRNA de GINS1, a expressão da proteína e a metilação do promotor foram analisados ​​usando UALCAN e Human Protein Atlas (HPA), enquanto a expressão de mRNA foi posteriormente validada via GENT2. Os valores prognósticos potenciais de GINS1 foram avaliados por meio do plotter KM. Em seguida, o cBioPortal foi utilizado para examinar as mutações genéticas relacionadas ao GINS1 e as variações do número de cópias (CNVs), enquanto a análise de enriquecimento da via foi realizada usando DAVID. Além disso, uma análise correlacional entre a expressão de GINS1 e células imunes T CD8 + e a construção de uma rede de interação gene-droga foi realizada usando TIMER, CDT e Cytoscape. O GINS1 foi encontrado regulado negativamente em um único subtipo de câncer humano, enquanto comumente regulado positivamente em 23 outros subtipos diferentes. A regulação positiva de GINS1 foi significativamente correlacionada com a sobrevida global pobre (OS) de Carcinoma Hepatocelular de Fígado (LIHC), Adenocarcinoma de Pulmão (LUAD) e Carcinoma de Células Claras Renais de Rim (KIRC). O GINS1 também foi encontrado regulado positivamente em pacientes LIHC, LUAD e KIRC de diferentes características clínico-patológicas. A análise de enriquecimento de vias revelou o envolvimento de GINS1 em duas vias diversas, enquanto poucas correlações interessantes também foram documentadas entre a expressão de GINS1 e seu nível de metilação do promotor, nível de células imunes T CD8 + e CNVs. Além disso, também previmos poucos medicamentos que poderiam ser usados ​​no tratamento de LIHC, LUAD e KIRC, regulando a expressão de GINS1. O perfil de expressão de GINS1 no estudo atual sugeriu que é um novo biomarcador de diagnóstico e prognóstico compartilhado de LIHC, LUAD e KIRC.

Is non-contrast-enhanced magnetic resonance imaging cost-effective for screening of hepatocellular carcinoma?

INTRODUCTION@#Ultrasonography (US) is the current standard of care for imaging surveillance in patients at risk of hepatocellular carcinoma (HCC). Magnetic resonance imaging (MRI) has been explored as an alternative, given the higher sensitivity of MRI, although this comes at a higher cost. We performed a cost-effective analysis comparing US and dual-sequence non-contrast-enhanced MRI (NCEMRI) for HCC surveillance in the local setting.@*METHODS@#Cost-effectiveness analysis of no surveillance, US surveillance and NCEMRI surveillance was performed using Markov modelling and microsimulation. At-risk patient cohort was simulated and followed up for 40 years to estimate the patients' disease status, direct medical costs and effectiveness. Quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio were calculated.@*RESULTS@#Exactly 482,000 patients with an average age of 40 years were simulated and followed up for 40 years. The average total costs and QALYs for the three scenarios - no surveillance, US surveillance and NCEMRI surveillance - were SGD 1,193/7.460 QALYs, SGD 8,099/11.195 QALYs and SGD 9,720/11.366 QALYs, respectively.@*CONCLUSION@#Despite NCEMRI having a superior diagnostic accuracy, it is a less cost-effective strategy than US for HCC surveillance in the general at-risk population. Future local cost-effectiveness analyses should include stratifying surveillance methods with a variety of imaging techniques (US, NCEMRI, contrast-enhanced MRI) based on patients' risk profiles.

Oncogenic β-catenin-driven liver cancer is susceptible to methotrexate-mediated disruption of nucleotide synthesis / 中华医学杂志(英文版)

BACKGROUND@#Liver cancer is largely resistant to chemotherapy. This study aimed to identify the effective chemotherapeutics for β-catenin-activated liver cancer which is caused by gain-of-function mutation of catenin beta 1 ( CTNNB1 ), the most frequently altered proto-oncogene in hepatic neoplasms.@*METHODS@#Constitutive β-catenin-activated mouse embryonic fibroblasts (MEFs) were established by deleting exon 3 ( β-catenin Δ(ex3)/+ ), the most common mutation site in CTNNB1 gene. A screening of 12 widely used chemotherapy drugs was conducted for the ones that selectively inhibited β-catenin Δ(ex3)/+ but not for wild-type MEFs. Untargeted metabolomics was carried out to examine the alterations of metabolites in nucleotide synthesis. The efficacy and selectivity of methotrexate (MTX) on β-catenin-activated human liver cancer cells were determined in vitro . Immuno-deficient nude mice subcutaneously inoculated with β-catenin wild-type or mutant liver cancer cells and hepatitis B virus ( HBV ); β-catenin lox(ex3)/+ mice were used, respectively, to evaluate the efficacy of MTX in the treatment of β-catenin mutant liver cancer.@*RESULTS@#MTX was identified and validated as a preferential agent against the proliferation and tumor formation of β-catenin-activated cells. Boosted nucleotide synthesis was the major metabolic aberration in β-catenin-active cells, and this alteration was also the target of MTX. Moreover, MTX abrogated hepatocarcinogenesis of HBV ; β-catenin lox(ex3)/+ mice, which stimulated concurrent Ctnnb1- activated mutation and HBV infection in liver cancer.@*CONCLUSION@#MTX is a promising chemotherapeutic agent for β-catenin hyperactive liver cancer. Since repurposing MTX has the advantages of lower risk, shorter timelines, and less investment in drug discovery and development, a clinical trial is warranted to test its efficacy in the treatment of β-catenin mutant liver cancer.

AZD1775 and anti-PD-1 antibody synergistically sensitize hepatoma to radiotherapy / 中华医学杂志(英文版)

BACKGROUND@#Radiation (IR)-induced DNA damage triggers cell cycle arrest and has a suppressive effect on the tumor microenvironment (TME). Wee1, a cell cycle regulator, can eliminate G2/M arrest by phosphorylating cyclin-dependent kinase 1 (CDK1). Meanwhile, programed death-1/programed death ligand-1 (PD-1/PDL-1) blockade is closely related to TME. This study aims to investigate the effects and mechanisms of Wee1 inhibitor AZD1775 and anti-PD-1 antibody (anti-PD-1 Ab) on radiosensitization of hepatoma.@*METHODS@#The anti-tumor activity of AZD1775 and IR was determined by 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyltetrazolium bromide (MTT) assay on human and mouse hepatoma cells HepG2, Hepa1-6, and H22. The anti-hepatoma mechanism of AZD1775 and IR revealed by flow cytometry and Western blot in vitro . A hepatoma subcutaneous xenograft mice model was constructed on Balb/c mice, which were divided into control group, IR group, AZD1775 group, IR + AZD1775 group, IR + anti-PD-1 Ab group, and the IR + AZD1775 + anti-PD-1 Ab group. Cytotoxic CD8 + T cells in TME were analyzed by flow cytometry.@*RESULTS@#Combining IR with AZD1775 synergistically reduced the viability of hepatoma cells in vitro . AZD1775 exhibited antitumor effects by decreasing CDK1 phosphorylation to reverse the IR-induced G2/M arrest and increasing IR-induced DNA damage. AZD1775 treatment also reduced the proportion of PD-1 + /CD8 + T cells in the spleen of hepatoma subcutaneous xenograft mice. Further studies revealed that AZD1775 and anti-PD-1 Ab could enhance the radiosensitivity of hepatoma by enhancing the levels of interferon γ (IFNγ) + or Ki67 + CD8 T cells and decreasing the levels of CD8 + Tregs cells in the tumor and spleen of the hepatoma mice model, indicating that the improvement of TME was manifested by increasing the cytotoxic factor IFNγ expression, enhancing CD8 + T cells proliferation, and weakening CD8 + T cells depletion.@*CONCLUSIONS@#This work suggests that AZD1775 and anti-PD-1 Ab synergistically sensitize hepatoma to radiotherapy by enhancing IR-induced DNA damage and improving cytotoxic CD8 + T cells in TME.

Strategies and advances in laboratory tests for primary liver cancer / 中华预防医学杂志

Primary liver cancer is one of the leading causes of cancer-related deaths worldwide, its early diagnosis and early treatment are of great clinical importance. The main detection tools for liver cancer include serological indicators, imaging tests and risk assessment models. With the advancement of technology and research, the sensitivity and specificity of laboratory tests for liver cancer have been substantially improved, but there are still false negatives and low rates of early diagnosis. For different causes and prevalence regions, each country has developed its clinical practice guidelines to guide risk groups for effective prevention, early diagnosis and standardized treatment. It is important to establish a liver cancer diagnosis strategy that is suitable for China's national conditions, concerning the guidelines for the vigilance and prevention of liver cancer. In this article, the advantages and disadvantages of liver cancer-related tests and the impact of future development trends on laboratory strategies are explained from the perspective of laboratory testing strategies, to provide theoretical support for the practical application of liver cancer diagnostic strategies.

Strategies and advances in laboratory tests for primary liver cancer / 中华预防医学杂志

Primary liver cancer is one of the leading causes of cancer-related deaths worldwide, its early diagnosis and early treatment are of great clinical importance. The main detection tools for liver cancer include serological indicators, imaging tests and risk assessment models. With the advancement of technology and research, the sensitivity and specificity of laboratory tests for liver cancer have been substantially improved, but there are still false negatives and low rates of early diagnosis. For different causes and prevalence regions, each country has developed its clinical practice guidelines to guide risk groups for effective prevention, early diagnosis and standardized treatment. It is important to establish a liver cancer diagnosis strategy that is suitable for China's national conditions, concerning the guidelines for the vigilance and prevention of liver cancer. In this article, the advantages and disadvantages of liver cancer-related tests and the impact of future development trends on laboratory strategies are explained from the perspective of laboratory testing strategies, to provide theoretical support for the practical application of liver cancer diagnostic strategies.

No Incidence of Liver Cancer Was Observed in A Retrospective Study of Patients with Aristolochic Acid Nephropathy / 中国结合医学杂志

OBJECTIVE@#To assess the risk of aristolochic acid (AA)-associated cancer in patients with AA nephropathy (AAN).@*METHODS@#A retrospective study was conducted on patients diagnosed with AAN at Peking University First Hospital from January 1997 to December 2014. Long-term surveillance and follow-up data were analyzed to investigate the influence of different factors on the prevalence of cancer. The primary endpoint was the incidence of liver cancer, and the secondary endpoint was the incidence of urinary cancer during 1 year after taking AA-containing medication to 2014.@*RESULTS@#A total of 337 patients diagnosed with AAN were included in this study. From the initiation of taking AA to the termination of follow-up, 39 patients were diagnosed with cancer. No cases of liver cancer were observed throughout the entire follow-up period, with urinary cancer being the predominant type (34/39, 87.17%). Logistic regression analysis showed that age, follow-up period, and diabetes were potential risk factors, however, the dosage of the drug was not significantly associated with urinary cancer.@*CONCLUSIONS@#No cases of liver cancer were observed at the end of follow-up. However, a high prevalence of urinary cancer was observed in AAN patients. Establishing a direct causality between AA and HCC is challenging.

Deep learning-based radiomics allows for a more accurate assessment of sarcopenia as a prognostic factor in hepatocellular carcinoma / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Hepatocellular carcinoma (HCC) is one of the most common malignancies and is a major cause of cancer-related mortalities worldwide (Forner et al., 2018; He et al., 2023). Sarcopenia is a syndrome characterized by an accelerated loss of skeletal muscle (SM) mass that may be age-related or the result of malnutrition in cancer patients (Cruz-Jentoft and Sayer, 2019). Preoperative sarcopenia in HCC patients treated with hepatectomy or liver transplantation is an independent risk factor for poor survival (Voron et al., 2015; van Vugt et al., 2016). Previous studies have used various criteria to define sarcopenia, including muscle area and density. However, the lack of standardized diagnostic methods for sarcopenia limits their clinical use. In 2018, the European Working Group on Sarcopenia in Older People (EWGSOP) renewed a consensus on the definition of sarcopenia: low muscle strength, loss of muscle quantity, and poor physical performance (Cruz-Jentoft et al., 2019). Radiological imaging-based measurement of muscle quantity or mass is most commonly used to evaluate the degree of sarcopenia. The gold standard is to measure the SM and/or psoas muscle (PM) area using abdominal computed tomography (CT) at the third lumbar vertebra (L3), as it is linearly correlated to whole-body SM mass (van Vugt et al., 2016). According to a "North American Expert Opinion Statement on Sarcopenia," SM index (SMI) is the preferred measure of sarcopenia (Carey et al., 2019). The variability between morphometric muscle indexes revealed that they have different clinical relevance and are generally not applicable to broader populations (Esser et al., 2019).

Research progress on immunotherapy based on NK cells for hepatocellular carcinoma / 细胞与分子免疫学杂志

Hepatocellular carcinoma (HCC) is well characterized as a heterogeneous disease. Its late-stage diagnosis and chemotherapy resistance make it one of the refractory tumors in China. Natural killer (NK) cells play a significant role in immune surveillance. However, NK cells become dysfunctional in the progression of HCC, leading to tumor immune escape. This article reviews the recent progress on different strategies of NK cell-based immunotherapy in treating HCC, including direct adoptive NK cell transfer, gene engineering in NK cell, NK cell receptor targeting, immunosuppressive microenvironment modification, and tumor toxicity enhancement by cytokines or traditional Chinese medicine. These NK cell-based strategies have shown promising therapeutic potential.

Neoplasia quística mucinosa hepática, reporte de un caso y análisis de la patología / Hepatic mucinous cystic neoplasm, case report and pathology analysis / Neoplasia cística mucinosa hepática, relatório de um caso e análise da patologia

Desde los primeros reportes en la bibliografía, la nomenclatura de las lesiones quísticas hepatobiliares se ha ido modificando, habiéndose descripto dos tipos de lesiones: las serosas y las mucinosas. En 2010 la Organización Mundial de la Salud estableció una nueva clasificación donde los términos cistoadenomas y cistoadenocarcinomas hepatobiliares son reemplazados por entidades más específicas como la neoplasia mucinosa quística y los tumores quísticos intraductales (neoplasia papilar intraductal, neoplasma tubulopapilar intraductal y neoplasma oncocitico papilar). En cuanto a la neoplasia mucinosa quística, la presencia de estroma ovárico le confiere características distintivas en lo patológico y biológico, siendo esto un requisito en la clasificación de la OMS. Esta característica lo diferencia de los hamartomas biliares, los quistes congénitos y la enfermedad de Caroli. Dichas neoplasias son infrecuentes, con una incidencia menor al 5% de las lesiones quísticas hepáticas y ocurren casi exclusivamente en mujeres, frecuentemente perimenopáusicas. Su potencial de malignización ha sido descrito, siendo éste la indicación de tratamiento quirúrgico resectivo. Presentamos el caso clínico de una paciente portadora de una neoplasia quística mucinosa hepática, catalogada como cistoadenoma hepático según la antigua clasificación.

Since the early reports in the literature, the nomenclature of hepatobiliary cystic lesions has been modified, with two types of lesions being described: serous and mucinous. In 2010, the World Health Organization established a new classification in which the terms hepatobiliary cystadenomas and cystadenocarcinomas were replaced by more specific entities such as mucinous cystic neoplasms and intraductal cystic tumors (intraductal papillary neoplasm, intraductal tubulopapillary neoplasm, and intraductal oncocytic papillary neoplasm). Regarding mucinous cystic neoplasms, the presence of ovarian stroma confers distinctive pathological and biological characteristics, which is a requirement in the WHO classification. This characteristic differentiates it from biliary hamartomas, congenital cysts, and Caroli's disease. Such neoplasms are rare, with an incidence of less than 5% of hepatic cystic lesions, and occur almost exclusively in women, often perimenopausal. Their potential for malignancy has been described, and this is the indication for surgical resection treatment. We present a clinical case of a patient with a mucinous cystic hepatic neoplasm, classified as a hepatic cystadenoma according to the old classification.

Desde os primeiros relatos na literatura, a nomenclatura das lesões císticas hepatobiliares tem sido modificada, sendo descritos dois tipos de lesões,asserosas e as mucinosas. Em 2010, a Organização Mundial da Saúdeestabeleceuuma nova classificação, naqual os termos cistoadenomas e cistoadenocarcinomas hepatobiliares foramsubstituídos por entidades mais específicas, como a neoplasia mucinosa cística e os tumores císticos intraductais (neoplasia papilar intraductal, neoplasma tubulopapilar intraductal e neoplasma oncocítico papilar). Em relação à neoplasia mucinosa cística, a presença de estroma ovarianoconfere características distintas do ponto de vista patológico e biológico, sendoesseum requisito naclassificação da OMS. Essa característica a diferencia dos hamartomas biliares, cistoscongênitos e doença de Caroli. Essas neoplasias são raras, comumaincidência menor que 5% das lesões císticas hepáticas, e ocorremquase exclusivamente em mulheres, frequentementeperimenopáusicas. Seu potencial de malignizaçãotem sido descrito, sendoesta a indicação para tratamentocirúrgicoressectivo. Apresentamos o caso clínico de uma paciente portadora de uma neoplasia cística mucinosa hepática, classificada como cistoadenoma hepático de acordocom a antigaclassificação.

Adenoma Hepatocelular: a propósito de un caso / Hepatocellular adenoma: about a case / Adenoma hepatocelular: sobre um caso

El Adenoma Hepatocelular (AH) es un tumor hepático benigno, su diagnóstico ha avanzado gracias a los avances en los métodos moleculares, facilitaron dividirlos en subtipos, con diferentes pronósticos e indicaciones terapéuticas. Se presenta el caso clínico de una paciente, de 40 años con hallazgo ecográfico de tumor hepático, la Tomografía de Abdomen y Pelvis voluminosa lesión sólida heterogénea, en la Resonancia Magnética compatible con Adenoma esteatósico (asociado a mutación HNF1 alfa). Se decide tratamiento quirúrgico, con resección de los segmentos 6 y 7. La Anatomía patológica concluye: Compatible con el subtipo inflamatorio. Los Adenoma hepáticos (AH) son tumores raros, solitarios de estirpe epitelial, benignos. Se presentan en mujeres de edad fértil y asociado al consumo de anticonceptivos orales y estrógenos. Estos tumores predominan en hígado derecho, con proliferación de células parecidas a los hepatocitos normales, pero desorganizados y sin arquitectura lobular normal, sin ductos biliares ni tejido conectivo de sostén. Los AH así como el resto de los tumores hepáticos benignos, han aumentado su incidencia de la mano con el avance de la imagenología abdominal. La importancia de la diferenciación con el resto de los tumores hepáticos benignos surge del potencial maligno de éstos. Podemos clasificar a los pacientes según el perfil molecular asociado a marcadores inmunohistoquímicos. Los estudios de imagen son fundamentales para la diferenciación tumoral en diagnóstico y planear la terapéutica. El tratamiento será individualizado, determinada por la clínica, la variedad de subtipos, y la evolución. Debido a la complejidad de la enfermedad, el tratamiento de la HA es uno de los mejores ejemplos de abordaje individualizado en unidades hepatobiliares.

Hepatocellular adenoma (HA) is a benign liver tumor, its diagnosis has advanced thanks to advances in molecular methods, which facilitated its division into subtypes, with different prognoses and therapeutic indications. We present the clinical case of a 40-year-old patient with an ultrasound finding of a liver tumor, a voluminous heterogeneous solid lesion on a CT scan of the abdomen and pelvis, compatible with a steatotic adenoma on MRI (associated with HNF1 alpha mutation). Surgical treatment was decided, with resection of segments 6 and 7. The pathology concluded in short: Compatible with the inflammatory subtype. Hepatic adenomas (HA) are rare, solitary, benign epithelial tumors. They occur in women of childbearing age and associated with the consumption of oral contraceptives and estrogens. These tumors predominate in the right liver, with proliferation of cells similar to normal hepatocytes, but disorganized and without normal lobular architecture, without bile ducts or supporting connective tissue. HA, as well as the rest of the benign liver tumors, have increased their incidence in the hand with the advancement of abdominal imaging. The importance of differentiation with the rest of the benign liver tumors arises from the malignant potential of these. We can classify patients according to the molecular profile associated with immunohistochemical markers. Imaging studies are fundamental for tumor differentiation in diagnosis and therapeutic planning. The treatment will be individualized, determined by the clinic, the variety of subtypes, and the evolution. Due to the complexity of the disease, the treatment of AH is one of the best examples of an individualized approach in hepatobiliary units.

O adenoma hepatocelular (AH) éum tumor benigno do fígado, seu diagnóstico avançougraçasaosavanços dos métodos moleculares, que facilitaramsuadivisão em subtipos, com diferentes prognósticos e indicaçõesterapêuticas. Apresentamos o caso clínico de umadoente de 40 anoscomachadoultrassonográfico de tumor hepático, volumosalesão sólida heterogénea à TC de abdómen e pelve, compatívelcom adenoma esteatótico à RM (associado a mutação HNF1 alfa ). Optou-se por tratamentocirúrgico, comressecção dos segmentos 6 e 7. A patologiaconcluiu-se resumidamente: Compatívelcom o subtipo inflamatório. Os adenomas hepáticos (AH) são tumores epiteliais raros, solitários e benignos. Ocorrem em mulheres em idadereprodutiva e associadasao consumo de anticoncepcionaisorais e estrogênios. Esses tumores predominam no fígadodireito, comproliferação de células semelhantesaoshepatócitosnormais, porém desorganizados e semarquitetura lobular normal, sem ductos biliares outecido conjuntivo de sustentação. O HA, assim como os demais tumores hepáticos benignos, têm aumentado suaincidêncianamãocom o avanço da imagem abdominal. A importância da diferenciaçãocom os demais tumores hepáticos benignos decorre do potencial maligno destes. Podemos classificar os pacientes de acordocom o perfil molecular associado a marcadores imuno-histoquímicos. Os estudos de imagemsãofundamentais para a diferenciação tumoral no diagnóstico e planejamentoterapêutico. O tratamento será individualizado, determinado pela clínica, variedade de subtipos e evolução. Pela complexidade da doença, o tratamento da HA é um dos melhoresexemplos de abordagem individualizada nas unidades hepatobiliares.

Clinical outcomes of the liver-first approach in the management of synchronous colorectal liver metastases: a retrospective study

Introduction: Almost 25% of colorectal cancer (CRC) patients have synchronous colorectal liver metastasis (SCLM) coinciding with the disease diagnosis. Liver-first approach for the treatment of SCLM involves neoadjuvant chemotherapy, subsequent liver resection, and then primary tumor resection. This strategy is adopted as the prognosis of the disease depends mainly on the metastases, not the primary tumor. This study aims to evaluate the feasibility of the liver-first approach and clinical prognosis in managing SCLM. Materials and Methods: This retrospective study included 25 patients with SCLM from July 2015 to July 2020. All patients were subjected to a liver-first approach with an "intention-to-treat" approach. Follow-up was planned for at least 3 years. Data were collected from the hospital records and included survival rates and univariate analyses of the prognostic factors, such as gender, age, and number of chemotherapy cycles to evaluate their effect on the survival probability. Results: Nineteen patients completed the treatment paradigm. Long-term outcomes reported a median overall survival (OS) of 32 months. One-year and 3-year survival probabilities were 89.5% and 42.1%, respectively. The median disease-free survival was 13 months. The number of metastatic lesions, unilobar versus bilobar disease, and the frequency of administered chemotherapy cycles significantly affected survival (p < 0.05). Seven patients (36.84%) remained disease free (no recurrence) while 2 patients (10.53%) survived with recurrence. The overall mortality included 10 deaths (52.63%) due to recurrence. Conclusion: Synchronous colorectal liver metastasis treated with the liver-first approach achieved a notable overall advantage. However, the recurrence rate remained relatively high. (AU)

Biliotórax: una entidad rara para un diagnóstico frecuente. Un reporte de caso / Bilothorax: a Rare Entity for a Frequent Diagnosis. A Case Report

Introducción: El biliotórax es una condición infrecuente definida por la presencia de bilis en el espacio pleural. Actualmente, hay alrededor de 70 casos descritos en la litera-tura. Sigue siendo relativamente desconocido, por lo tanto, poco sospechado. Esta entidad suele ser el resultado de una lesión iatrogénica, a menudo secundaria a cirugías o traumatismos del tracto biliar, que conduce a la formación de una fístula pleurobiliar.

Introduction: Bilothorax is a rare condition defined by the presence of bile in the pleural space. Currently, there are around 70 cases described in the literature. It remains relatively unknown and, therefore, little suspected. This entity is usually the result of an iatrogenic injury, often secondary to surgery or trauma to the biliary tract, leading to the formation of a pleurobiliary fistula

Metodologías de Medición de Volumetría Hepática / Methodologies For Measuring Hepatic Volumetry

Lograr determinar el volumen total de un hígado (VHT), o volumetría hepática, pasa a ser de relevancia en diversas situaciones, tales como, vigilancia del progreso de una enfermedad de carácter crónico, planificación de resecciones y trasplantes hepáticos; y observación del clearance hepático de algunos fármacos hepatotropos. La VHT se puede realizar utilizando métodos de segmentación en el curso de una tomografía computarizada (TC), ya sean estos manual, automáticos, y semiautomáticos; mediante resonancia nuclear (RN), utilizando softwares de distintas generaciones (1ª a 4ª). La medición de VHT está indicada en pacientes sometidos a resecciones hepáticas mayores, en el contexto del tratamiento de neoplasias (carcinoma hepatocelular, colangiocarcinoma, metástasis hepáticas o tumores benignos de gran tamaño), abscesos (piogénicos, amebianos), y después de un traumatismo hepático complejo; así como también en la etapa preoperatoria de un trasplante hepático. El objetivo de este manuscrito fue generar un documento de estudio sobre métodos para determinar volumetría hepática.

SUMMARY: Being able to determine the total hepatic volume (THV), or THV, becomes relevant in various situations, such as monitoring the progress of a chronic disease, planning resections and liver transplants; and observation of the hepatic clearance of some hepatotropic drugs. THV can be performed using segmentation methods in the course of a computed tomography (CT), whether manual, automatic, or semi-automated; by nuclear resonance (NR), using software from different generations (1st to 4st). THV measurement is indicated in patients undergoing major liver resections, in the context of treatment of neoplasms (hepatocellular carcinoma, cholangiocarcinoma, liver metastases or large benign tumors), abscesses (pyogenic, amoebic), and after liver trauma complex, as well as in the preoperative stage of a liver transplant. The aim of this manuscript was to generate a study document regarding methods for determine hepatic volumetry.

Resecabilidad de las metástasis hepáticas según la lateralidad del tumor colorrectal primario y la temporalidad de presentación. Serie de casos en dos instituciones de alta complejidad de la ciudad de Medellín / Resectability of liver metastasis according to the laterality of the primary colorectal tumor and the temporality of presentation. Case series in two high-complex institutions in the city of Medellín

Introducción. La neoplasia colorrectal es una patología oncológica muy frecuente a nivel mundial y una de las causas más comunes de mortalidad por cáncer. La epidemiologia, diagnóstico y tratamiento han sido ampliamente estudiadas, mientras que los datos sobre la enfermedad metastásica siguen siendo escasos. El hígado es el órgano más comúnmente afectado y algunos estudios sugieren diferencias en sobrevida y resecabilidad según la localización del tumor primario. El objetivo de este estudio fue establecer el comportamiento y resecabilidad de neoplasias avanzadas colorrectales en dos hospitales de la ciudad de Medellín, Colombia. Métodos. Estudio analítico retrospectivo para identificar los patrones de las metástasis hepáticas y sus características en función de las diferencias clínicas, histológicas y endoscópicas del tumor colorrectal primario entre 2015 y 2020. Resultados. Se recolectaron 54 pacientes con neoplasia colorrectal y metástasis hepáticas, 21 (39 %) derechas y 33 (61 %) izquierdas. El número de metástasis promedio fue de 3,1 en tumores del lado derecho y de 2,4 del izquierdo y el tamaño promedio de cada lesión fue de 4,9 y 4,2 cm, respectivamente. La tasa de resecabilidad fue del 42 % en los tumores derechos y del 82 % en los izquierdos. Las lesiones metacrónicas presentaron una tasa de resecabilidad del 90 % y las sincrónicas del 61 %. Conclusión. En este estudio, las lesiones originadas en neoplasias primarias del colon izquierdo y las lesiones metacrónicas fueron factores pronósticos favorables para la resecabilidad, un factor que impacta en la sobrevida y el tiempo libre de enfermedad de estos pacientes.

Introduction. Colorectal tumor is the most frequent pathology worldwide and one of the most common causes of mortality attributed to cancer. Epidemiology, diagnosis and treatment have been extensively studied, while information on metastatic disease remains scarce, despite being the main cause of death. Some studies suggest differences in terms of survival and resectability according to the anatomical location of the primary tumor. The aim is to establish the behavior and resectability of advanced cancers in two high-complex hospitals in the city of Medellín, Colombia. Methods. Cross-sectional observational study from secondary sources of information based on a retrospective cohort, using available data from adult patients with colorectal cancer and liver metastases between 2015 and 2020. Results. Fifty-four patients with colorectal neoplasms and liver metastases were collected, of which 21 (39%) were on the right side. The average number of liver metastases was 3.1 on the right side and 2.4 on the left, and the average size of each metastatic lesion was 4.9 cm and 4.2 cm, respectively. The resectability rate was 42% in the right tumors and 82% in the left ones. Metachronous lesions had a resectability rate of 90% and synchronous ones 61%. Conclusion. The complete resectability of liver metastatic lesions is the only therapeutic alternative with impact, in terms of survival and disease-free time in these patients. The favorable prognostic factors for the resectability of these lesions in our study were those originating from left primary tumors and metachronous lesions, where less liver tumor involvement was evidenced

Pseudotumor inflamatorio hepático: caso clínico y revisión de la literatura / Hepatic Inflammatory Pseudotumor Mimicking Cholangiocarcinoma: A Rare Case and Literature Review

Presentamos el caso de un paciente de 49 años, de sexo masculino, que consulta en el servicio de urgencias por un cuadro de dos meses de evolución, caracterizado por compromiso del estado general, baja de peso, dolor abdominal, sensación febril y elevación de los parámetros inflamatorios. Al estudio imagenológico se observa una voluminosa lesión hepática, asociada a dilatación de la vía biliar y adenopatías en hilio hepático, espacio porto-cavo y retroperitoneales (inter-cavo-aórticos), que plantea dentro de los diagnósticos diferencias un colangiocarcinoma intrahepático. Basados en esta sospecha se realiza una segmentectomía y linfadenectomía regional. El estudio histopatológico e inmunohistoquímico de la pieza quirúrgica, evidencia un proceso inflamatorio linfoplasmocitario, con la presencia de células plasmáticas IgG4 positivas, compatible con una enfermedad asociada a IgG4. Posterior a la resección se decide manejo expectante, evolucionando el paciente de forma favorable, asintomático y sin signos de recurrencia. Presentamos un caso y una breve revisión de la literatura de un pseudotumor inflamatorio hepático, entidad poco frecuente y de comportamiento benigno.

We report the case of a 49-year-old man who attended the emergency department for a two-month history of compromised general condition, weight loss, abdominal pain, fever, and elevated inflammatory parameters. An imaging study demonstrates a bulky liver tumor associated with dilation of the bile duct and retroperitoneal adenopathies (hepatic hilum, intermediate, and right lumbar groups). These findings raise intrahepatic cholangiocarcinoma within the differential diagnoses, reason why segmental hepatectomy and regional lymphadenectomy were performed. Histopathology and immunochemistry revealed a lymphoplasmacytic inflammatory process with IgG4-positive plasma cells compatible with IgG4-associated disease. After the resection, expectant management was decided, with the patient evolving favorably, asymptomatic, and without signs of recurrence. We present a case and a brief literature review of an hepatic inflammatory pseudotumor, a rare entity with a benign behavior.

Evolução da mortalidade por neoplasias entre os anos de 2010 a 2020 no Brasil segundo sexo e localização primária do tumor / Evolution of mortality from neoplasms between the years 2010 to 2020 in Brazil according to gender and primary location of the tumour

Introdução: o câncer é um grave problema de saúde pública, considerado a segunda causa de óbitos no Brasil. Devido à sua relevância, é indispensável um controle eficiente dos casos através do acompanhamento da taxa de mortalidade. Dessa forma, o trabalho analisou a evolução da mortalidade por câncer para as localizações primárias mais frequentes, segundo sexo, durante o período de 2010 a 2020. Metodologia: trata-se de um estudo observacional descritivo, no qual os dados foram obtidos através do Atlas On-line de Mortalidade por Câncer. Os dados colhidos correspondem ao número de óbitos estratificados por tipo de câncer mais frequente, por ano estudado e por sexo, além das taxas de mortalidade específica bruta e a taxa de mortalidade ajustada por idade para o sexo masculino e feminino, para cada tipo de câncer em estudo, considerando a população padrão mundial, sendo avaliado por regressão linear a significância da tendência temporal. Resultados: no Brasil, no período de 2010 a 2020, as neoplasias mais frequentes em mulheres foram câncer de mama, câncer nos brônquios e pulmões, câncer no colo do útero, câncer no cólon e no pâncreas e em homens foram brônquios e pulmões, câncer de próstata, câncer de estômago, de esôfago e no fígado e vias biliares, sendo observado uma tendência crescente na taxa de mortalidade em mulheres e decrescente na taxa de mortalidade em homens. Conclusão: os resultados demonstram um possível comprometimento com a notificação durante o período de pandemia por Covid-19 e um possível rastreamento ainda deficiente de câncer na população masculina.

Introduction: cancer is a severe public health problem, considered the second cause of death in Brazil. Due to its relevance, efficient control of cases by monitoring the mortality rate is essential. Thus, the work analysed the evolution of cancer mortality for the most frequent primary locations, according to sex, from 2010 to 2020. Methodology: this is a descriptive observational study in which data were obtained through the Atlas Online Cancer Mortality Report. The data collected correspond to the number of deaths stratified by the most frequent type of cancer, by year studied and by sex, in addition to the crude specific mortality rates and the age-adjusted mortality rate for males and females, for each type of cancer. Understudy, considering the standard world population, the significance of the temporal trend is evaluated by linear regression. Results: in Brazil, from 2010 to 2020, the most frequent neoplasms in women were breast cancer, bronchial and lung cancer, cervical cancer, colon and pancreas cancer and in men, they were bronchial and lung cancer, cancer prostate, stomach, oesophagal and liver and biliary tract cancer, with an increasing trend in the mortality rate in women and a decreasing trend in the mortality rate in men. Conclusion: the results demonstrate a possible compromise with notification during the Covid-19 pandemic and a possible still poor screening of cancer in the male population.