Colangiocarcinoma tubulopapilar, una entidad emergente poco frecuente, a propósito de un caso

Objetivo: realizar una revisión bibliográfica y presentación de caso de colangiocarcinoma tubulopapilar. Material y Método: Se revisó la ficha médica y las características clínicas, radiológicas y patológicas del tumor, y la literatura científica respecto al carcinoma tubulopapilar. Caso Clínico: Paciente con ictericia progresiva asociado a baja de peso. El estudio imagenológico muestra amputación del tercio distal del colédoco por tejido de partes blandas, sugerente de colangiocarcinoma. Se realiza endosonografía, arrojando "fragmentos superficiales de adenocarcinoma tubulopapilar". Se realiza duodenopancreatectomía cefálica y, posteriormente, se inicia quimioterapia. Discusión: El colangiocarcinoma es una neoplasia de la vía biliar. Existen diferentes variantes histológicas, entre ellas el colangiocarcinoma tubulopapilar. Su diagnóstico se basa en estudios imagenológicos y anatomopatológicos. El principal hallazgo imagenológico va a depender del patrón de crecimiento tumoral; masiforme, periductal o intraductal. Dentro de los intraductales, se describe un carcinoma biliar con crecimiento tubulopapilar, con fenotipo pancreatobiliar epitelial. En los últimos años han sido de interés por tener mejor pronóstico. Conclusión: El colangiocarcinoma tubulopapilar es una variante histológica poco frecuente del colangiocarcinoma, que se asocia a un mejor pronóstico que otras variantes.

Objective: To conduct a literature review and present a case study of tubulopapillary cholangiocarcinoma. Material and Method: The clinical record and the clinical, radiological, and pathological characteristics of the tumor were reviewed, along with the scientific literature regarding tubulopapillary carcinoma. Case Report: Patient with progressive jaundice associated with weight loss. Imaging studies show amputation of the distal third of the common bile duct by soft tissue, suggestive of cholangiocarcinoma. Endosonography was performed, yielding "superficial fragments of tubulopapillary adenocarcinoma." Subsequently, a cephalic duodenopancreatectomy is performed, followed by chemotherapy. Discussion: Cholangiocarcinoma is a neoplasm of the biliary tract. There are different histological variants, including tubulopapillary cholangiocarcinoma. Its diagnosis is based on imaging and pathological studies. The main imaging finding will depend on the pattern of tumor growth: mass-forming, periductal, or intraductal. Among the intraductal types, a biliary carcinoma with tubulopapillary growth and an epithelial pancreatobiliary phenotype has been described. In recent years, they have been of interest due to their better prognosis. Conclusion: Tubulopapillary cholangiocarcinoma is a rare histological variant of cholangiocarcinoma that is associated with a better prognosis than other variants.

Role of exosomes in intrahepatic cholangiocarcinoma / 临床肝胆病杂志

Intrahepatic cholangiocarcinoma （ICC） is a special type of liver cancer with atypical clinical symptoms in the early stage， and most patients are already in the advanced stage at the time of initial diagnosis. Due to a lack of effective molecular markers and treatment options， ICC patients tend to have an extremely low five-year survival rate. Exosomes are vesicles secreted by cells that contain proteins， RNA， and lipids， and they are important carriers of intercellular communication. Recent studies have shown that exosomes play a crucial role in the development and progression of ICC， and this article reviews the role and mechanism of exosomes in the diagnosis and treatment of ICC and looks into the future treatment prospect and potential clinical application of exosomes.

The biological function and mechanism of IDH1 gene in intrahepatic cholangiocarcinoma cell HuCCT1 / 解放军医学杂志

Objective To explore the role and possible molecular mechanism of Isocitrate dehydrogenase 1(IDH1)gene in proliferation and migration of intrahepatic cholangiocarcinoma(iCCA)cell HuCCT1.Methods HuCCT1 cells with IDH1 gene knockout(HuCCT1IDH1-/-)were constructed by CRISPR/Cas9 gene editing technology.To investigate the capacities of proliferation,migration and invasion of HuCCT1WT(HuCCT1 cells with wild-type IDH1 gene)and HuCCT1IDH1-/-cells,assays of CCK-8,clone formation,scratch and transwell were performed.Western blotting was used to detect the expression levels of epithelial-mesenchymal transition(EMT)associated proteins E-cadherin,N-cadherin,Vimentin,MMP-9,Wnt3a and β-catenin in two groups of cells.The transcriptome sequencing data of HuCCT1WT and HuCCT1IDH1-/-cells were analyzed by bioinformatics methods,Western blotting was used to verify the expression of signaling pathway-related proteins.Results Compared with HuCCT1WT cells,HuCCT1IDH1-/-cells showed the number of proliferation and clone formation significantly reduced(P<0.05),the proportion of cells blocked in G2/M phase was significantly increased(P<0.01),the rate of scratch healing was significantly decreased(P<0.01),and the number of migrated cells(P<0.001)and invaded cells(P<0.05)was significantly reduced.qRT-PCR assay showed that the expression levels of IDH1,Vimentin,MMP-9 and genes related to the regulation of G2/M cycle proliferation,Cyclin A2,Cyclin B1 and CDK1 mRNA were down-regulated in HuCCT1IDH1-/-cells(P<0.05),and the expression of CDH1 mRNA encoding E-cadherin was up-regulated(P<0.01);Western blotting assay showed that the expression level of E-cadherin in HuCCT1IDH1-/-cells was significantly increased(P<0.05),and the expression level of N-cadherin,Vimentin and MMP-9 protein was significantly decreased(P<0.05)than that in HuCCT1WT cells.Data of transcriptome sequencing revealed 1476 differentially expressed genes(DEGs)between two groups of HuCCT1 cells.Go enrichment analysis showed the DEGs were significantly enriched in cell biological processes associated with inflammatory response,cell signaling and cell metabolism.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis suggested that the DEGs may be involved in some signaling pathways such as Wnt,MAPK,Rap1,Hippo and TNF,which are closely related to the regulation of proliferation and invasion of tumor cells.Western blotting verification results showed that compared with HuCCT1WT cells,the relative expression of Wnt3a and β-catenin proteins of HuCCT1IDH1-/-cells was significantly decreased(P<0.05).Conclusions IDH1 gene may participate in the control of biological functions of HuCCT1 cells,including cell proliferation,migration,invasion and epithelial mesenchymal transition.The mechanism may be related to the activation of the Wnt/β-catenin signaling pathway.

Establishment and validation of a risk prediction model combined CT-radiomics and clinical features for lymph node metastasis in hilar cholangiocarcinoma / 中华放射学杂志

Objective:To establish and validate a clinical and CT radiomics combined model for predicting lymph node metastasis (LNM) risk in patients with hilar cholangiocarcinoma (HCCA).Methods:This was a case-control study. Data from 158 pathologically confirmed HCCA patients between January 2016 and January 2022 at the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. Using stratified random sampling, the patients were randomly divided into a training set ( n=95) and an internal validation set ( n=63) at a 6∶4 ratio. According to postoperative pathology, 31 LNM-positive cases and 64 LNM-negative cases were in the training set, and 22 LNM-positive cases and 41 LNM-negative cases were in the internal validation set. A cohort of 50 HCCA patients was retrospectively collected from West China Hospital of Sichuan University between October 2018 and June 2021 as an external validation set, including 21 LNM-positive and 29 LNM-negative cases. Clinical features were selected by multivariate logistic regression analysis to establish a clinical model. Radiomics features were extracted from portal venous phase CT images using 3D Slicer software. A radiomics model was developed using the least absolute shrinkage and selection operator regression algorithm. A clinical-radiomics model was constructed by integrating clinical features and Radscore, and a nomogram was developed. The prediction performance of models was evaluated by the area under the receiver operating characteristic curve (AUC). The AUC values were compared using the DeLong test. Calibration curves and decision curves were plotted to assess calibration and clinical net benefit. Results:Clinical N (cN) staging was an independent risk factor for LNM ( OR=6.86, 95% CI 2.70-18.49, P<0.001). Totally 12 optimal features were selected to construct the radiomics model, and the clinical-radiomics nomogram model was constructed by combining cN staging and Radscore. In the external validation set, the AUC (95% CI) of the clinical model, radiomics model, and clinical-radiomics nomogram were 0.706 (0.576-0.836), 0.768 (0.637-0.899), and 0.803 (0.680-0.926), respectively. The nomogram achieved higher AUC than clinical and radiomics models with statistical significance ( Z=2.01, 2.21; P=0.044, 0.027). The calibration and decision curves demonstrated good model fit, providing clinical net benefits for patients. Conclusion:The clinical-radiomics nomogram model combining cN staging and CT radiomics features can effectively predict LNM risk in HCCA patients.

Risk factors and prognosis of recurrence within 6 months after radical resection of intrahepatic cholangiocarcinoma / 中华普通外科杂志

Objective:To explore the relevant risk factors and prognosis of patients with intrahepatic cholangiocarcinoma (ICC) who experienced recurrence within 6 months after surgeryMethods:This retrospective study included a total of 259 patients with ICC a treated at He'nan Provincial People's Hospital and He'nan Cancer Hospital from Jan 2018 to Jan 2020. The clinical and pathological data ,differences between the group with recurrence within 6 months and the group without recurrence within 6 months were compared using the chi-square test. Logistic regression analysis was used to determine the relevant risk factors for recurrence within 6 months. Kaplan-Meier method was used to construct survival and recurrence curves, and survival rates were calculated.Results:The overall survival and recurrence-free survival of patients in the group with recurrence within 6 months were significantly shorter. CA19-9, tumor longitudinal diameter, microvascular invasion, and neural invasion were identified as independent risk factors for recurrence within 6 months after ICC surgery ( P<0.001). Conclusion:The patient population experiencing recurrence within 6 months after ICC surgery has an extremely poor prognosis and possesses a specific tumor microenvironment. CA19-9, tumor longitudinal diameter, microvascular invasion, and neural invasion were identified as independent risk factors for recurrence within 6 months after ICC surgery.

Expression of Midkine in cholangiocarcinoma and its value in predicting prognosis based on bioinformatics analysis / 临床肝胆病杂志

ObjectiveTo investigate the expression of Midkine （MDK） in cholangiocarcinoma （CCA） and its value in predicting the prognosis of CCA， as well as the potential mechanism of the effect of MDK on the progression of CCA. MethodsThe data of CCA samples were obtained from TCGA database to analyze the difference in the expression of MDK between cancer tissue and paracancerous tissue and its association with clinical features， and the data collected from GEO database and 11 CCA patients who underwent surgical resection in The Fifth Medical Center of Chinese PLA General Hospital from June 2018 to September 2021 were used for validation. STRING and Cytoscape were used to construct a protein-protein interaction network， and gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses were used to investigate the biological functions and tumor-related pathways involving MDK-related genes. In addition， TIMER and TISIDB databases were used to analyze the correlation between MDK expression and immune cell infiltration in CCA tissue. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the Fisher’s exact test was used for comparison of categorical data between two groups. The Kaplan-Meier method was used to plot survival curves， and the Log-rank test was used for comparison between groups. The Spearman correlation analysis was used to investigate the correlation between two variables. ResultsThe expression level of MDK in cancer tissue and paracancerous tissue of CCA patients was compared based on TCGA database， and the results of the non-paired and paired analyses showed that the expression level of MDK in CCA tumor tissue was significantly higher than that in paracancerous tissue （P<0.001）. Transcriptome sequencing was performed for the tumor tissue and its corresponding paracancerous tissue from 11 CCA patients， and the results showed that the expression level of MDK in CCA tumor tissue was significantly higher than that in corresponding paracancerous tissue （P<0.01）. High expression of MDK was associated with lymph node metastasis （P=0.045） and vascular invasion （P=0.044）. Survival analysis showed that compared with the CCA patients with low MDK expression， the CCA patients with high MDK expression had significantly shorter overall survival time （χ2=5.30， P=0.028） and disease-specific survival time （χ2=6.25， P=0.019）. The GO and KEGG enrichment analyses showed that the 30 MDK-related genes were closely associated with ubiquitin-mediated proteolysis and affected the prognosis of CCA patients. The TIMER analysis showed that the expression level of MDK was positively correlated with the infiltration of B cells （r=0.356， P=0.035 6） and dendritic cells （r=0.409， P=0.014 7） in tumor microenvironment of CCA； the TISIDB analysis showed that the expression level of MDK was positively correlated with CXCL16 （r=0.465， P=0.004 67） and was negatively correlated with CXCL12 （r=-0.389， P=0.019 7） and CXCR5 （r=-0.393， P=0.018 5）， and it was also negatively correlated with the immune checkpoint regulators VTCN1 （r=-0.393， P=0.018 3）， LTA （r=-0.380， P=0.022 7）， and PVR （r=-0.350， P=0.037 3）. ConclusionHigh expression of MDK is associated with poor prognosis in CCA patients， and MDK has the potential of being used as a molecular marker for predicting the prognosis of CCA. MDK may promote the development and progression of CCA by regulating ubiquitin-mediated proteolysis and the infiltration of B cells and dendritic cells.

Advances in the diagnosis and treatment of intrahepatic cholangiocarcinoma / 临床肝胆病杂志

Intrahepatic cholangiocarcinoma （ICC） is a relatively rare type of primary liver cancer， and its incidence rate has gradually increased in recent years. Due to its insidious onset and atypical clinical symptoms， most patients are already in the advanced stage of the disease at the time of confirmed diagnosis， and therefore， timely diagnosis and treatment are of great importance. Radical surgical resection is the standard treatment regimen for early-stage ICC patients， while systemic chemotherapy is the basic treatment for patients with advanced ICC and is often combined with interventional treatment， targeted therapy， and immunotherapy. This article reviews the advances in the diagnosis and treatment of ICC.

Recommendations from Annals of Surgical Oncology： Clinical guidelines for extrahepatic cholangiocarcinoma and gallbladder carcinoma / 临床肝胆病杂志

Biliary tract carcinoma （BTC） is a type of gastrointestinal tumor with a low incidence rate and a strong invasive ability， mainly including intrahepatic cholangiocarcinoma （ICC）， extrahepatic cholangiocarcinoma （ECC）， and gallbladder carcinoma （GC）， often accompanied by local progression or distant metastasis. Surgery is often the preferred treatment method for patients with local resectable tumor； however， there is still a high risk of recurrence after radical surgery. Therefore， multiple treatment modalities are often required for BTC patients， including surgical resection， systemic treatment （such as targeted therapy， chemotherapy， and immunotherapy）， and/or a combination of local treatment methods. With the development of the field of BTC， it is critical for surgical oncologists to understand and master the latest surgical strategies and the best patient selection and management systems. In view of the complexity of treatment and the continuous development of diagnosis and treatment techniques， Annals of Surgical Oncology， an authoritative American journal of cancer surgery， recently published the practical diagnosis and treatment guidelines for hepatobiliary tumors， including hepatocellular carcinoma （HCC）， ICC， ECC， and GC， aiming to provide more evidence-based evidence for the clinical management and decision-making of patients with hepatobiliary tumors. Due to the limitations of length and different emphases， this article mainly introduces the recommendations for the evaluation points and clinical treatment of ECC and GC in the guidelines， so as to provide a reference for clinical practice.

Pathogenesis of hepatitis B-associated intrahepatic cholangiocarcinoma / 临床肝胆病杂志

Intrahepatic cholangiocarcinoma （ICC） is a type of primary liver cancer that accounts for about 10%‍ — ‍15% of the total cases， and its incidence and mortality rates tend to increase significantly around the world， especially in Asian countries. At present， radical liver resection is the only possible cure for ICC， but with a fairly high postoperative recurrence rate and a poorer prognosis than hepatocellular carcinoma. Therefore， it is urgently needed to further investigate the mechanisms of the development and progression of ICC and search for more effective treatment methods. Some epidemiological data suggest that chronic hepatitis B virus infection is one of the most important predisposing factors for ICC， yet little is known about its oncogenic effects. This article summarizes the epidemiological evidence that links the two diseases and briefly elaborates on the mechanisms of the development and progression of HBV-associated ICC， so as to help to gain a better understanding of the role of HBV in the development and progression of ICC.

Mechanism of lncRNA MIR4435-2HG targeting miR-376a-3p to regulate the biological behavior of cholangio-carcinoma cells / 局解手术学杂志

Objective To explore the effects of long non-coding RNA(lncRNA)MIR4435-2HG(MIR4435-2HG)on the proliferation,migration,invasion and apoptosis of cholangiocarcinoma cells and its regulatory effect on microRNA-376a-3p(miR-376a-3p).Methods qRT-PCR method was used to detect the expression of MIR4435-2HG and miR-376a-3p in human intrahepatic bile duct epithelial cells HIBEpic and human cholangiocarcinoma cells RBE.si-NC,si-MIR4435-2HG,miR-NC,miR-376a-3p mimics,si-MIR4435-2HG and anti-miR-NC,and si-MIR4435-2HG and anti-miR-376a-3p were transfected into RBE cells,respectively,as the si-NC group,the si-MIR4435-2HG group,the miR-NC group,the miR-376a-3p group,the si-MIR4435-2HG+anti-miR-NC group,the si-MIR4435-2HG+ anti-miR-376a-3p group.MTT method,Transwell chamber method and flow cytometry were used to detect cell proliferation,migration,invasion and apoptosis;dual luciferase reporter gene assay was used to verify the targeting relationship between MIR4435-2HG and miR-376a-3p.Western blot was used to detect the expression of related proteins.Results The expression of MIR4435-2HG was increased in RBE cells,while the expression of miR-376a-3p was decreased(P<0.05).Compared with the si-NC group,the MIR4435-2HG expression,cell viability,and protein levels of CyclinD1,MMP-2,MMP-9 in the si-MIR4435-2HG group were reduced(P<0.05),the numbers of migrating and invading cells were reduced(P<0.05),while the MIR4435-2HG expression and apoptosis rate were increased(P<0.05).Compared with the miR-NC group,the cell viability and protein levels of CyclinD1,MMP-2,MMP-9 in the miR-376a-3p group were decreased(P<0.05),the numbers of migrating and invading cells were decreased(P<0.05),while the MIR4435-2HG expression and apoptosis rate were increased(P<0.05).MIR4435-2HG was of targeted regulation on miR-376a-3p.Compared with the si-MIR4435-2HG+ anti-miR-NC group,the cell viability and protein levels of CyclinD1,MMP-2,MMP-9 in the si-MIR4435-2HG+anti-miR-376a-3p group were increased(P<0.05),the numbers of migrating and invading cells were increased(P<0.05),while the MIR4435-2HG expression and apoptosis rate were decreased(P<0.05).Conclusion Knockdown of MIR4435-2HG can inhibit the proliferation,migration,invasion and induce apoptosis of RBE cells by targeting miR-376a-3p.

Mirizzi syndrome-differential diagnosis with cholangiocarcinoma: case report

Mirizzi syndrome is a rare complication of gallstone disease and poses a diagnostic challenge for general surgeons due to its clinical presentation, which resembles other pathological entities such as cholangiocarcinoma. We present a clinical case of a 68-year-old female patient with symptoms of jaundice and right upper quadrant pain. During the patient's diagnostic workup, altered liver function tests were documented, highlighting obstructive pattern hyperbilirubinemia, elevated tumor marker CA 19.9, and suspicion of biliary tract tumor based on imaging studies. However, surgical and pathological confirmation revealed Mirizzi syndrome. This case emphasizes the importance of considering differential diagnoses in patients presenting with obstructive jaundice to provide timely and appropriate treatment.

Comportamiento clínico-epidemiológico de los tumores periampulares malignos diagnosticados en Gastroenterología

Introducción: Los tumores malignos ubicados en la región periampular pueden ser: ampular, biliar, pancreático o duodenal, y constituyen un problema de salud por su alta mortalidad. En su etiopatogenia se involucran múltiples factores de riesgo, cuyo comportamiento clínico y epidemiológico se desconoce en la población matancera. Objetivo: Determinar el comportamiento clínico y epidemiológico de los tumores periampulares malignos. Materiales y métodos: Se realizó un estudio descriptivo, prospectivo en 34 pacientes con diagnóstico de tumores periampulares malignos, atendidos en el Servicio de Gastroenterología del Hospital Universitario Clínico Quirúrgico Comandante Faustino Pérez Hernández, de Matanzas, de enero a diciembre de 2021. Se estudiaron variables como: grupos de edad, sexo, factores de riesgo y antecedentes patológicos personales, tiempo de evolución de los síntomas y localización del tumor. Los resultados fueron recogidos en una planilla de recolección de datos. Resultados: Predominó el sexo masculino y el grupo de 50 a 69 años. Los factores de riesgo más frecuentes fueron el consumo de café, tabaquismo y diabetes mellitus. El íctero fue el síntoma más frecuente. La mayoría de los pacientes iniciaron los síntomas de 1 a 3 meses antes del diagnóstico. El cáncer de páncreas fue el más frecuente. Conclusiones: Los tumores periampulares predominaron en la población mayor de 50 años. Los hábitos tóxicos fueron los factores de riesgo más frecuentes. El cáncer de páncreas tuvo mayor incidencia. El comportamiento clínico estuvo relacionado con la localización de la lesión, el tiempo de evolución de los síntomas, y los factores de riesgo que predominaron.

Introduction: Malignant tumors located in the periampullary region can be ampullary, biliary, pancreatic or duodenal and are a health problem due to their high mortality. Their etio-pathogenesis involves many risk factors, whose clinic and epidemiological behavior is unknown by the population of Matanzas. Objective: To determine the clinical-epidemiological behavior of malignant periampullary tumors. Materials and methods: A descriptive, prospective study was conducted in 34 patients with diagnosis of malignant periampullary tumors, treated in the Gastroenterology Service of the Clinical-Surgery University Hospital Comandante Faustino Perez Hernandez, of Matanzas, from January to December 2021. Variables such as age group, sex, risk factors and personal pathological history, time of evolution of symptoms and tumor location were studied. The results were collected in a data collection form. Results: Male sex and the 50-69 years age group predominated. The most frequent risk factors were coffee consumption, smoking and diabetes mellitus. Jaundice was the most frequent symptom. Most of the patients started symptoms one to three months before the diagnosis. Pancreatic cancer was the most frequent. Conclusions: Periampullary tumors predominated in the population older than 50 years. Toxic habits were the most common risk factors. Pancreatic cancer had a higher incidence. Clinical behavior was related to the location of the lesion, the time of evolution of the symptoms, and the risk factors that predominated.

Isolated IgG4-related sclerosing cholangitis mimicking hilar cholangiocarcinoma: a case report of a challenging disease

IgG4-related disease (IgG4-RD) has recently attracted attention worldwide; however, its diagnosis still remains challenging. It is an immune-mediated multisystem disease affecting a wide range of organs in the human body. Even though it's uncommon, IgG4-sclerosing cholangitis, which is a biliary manifestation of IgG4-RD, can happen without pancreatic involvement. Here, we report a case of a patient with imaging features typical of hilar cholangiocarcinoma, which eventually turned out to be IgG4 sclerosing cholangitis.

Carcinoma de vías biliares intrahepáticas: análisis de defunciones según sexo, grupo etario y regiones en Chile entre 2017-2021 / Intrahepatic bile duct carcinoma: analysis of deaths according to sex, age group, and regions in Chile between 2017-2021

Introducción: el colangiocarcinoma intrahepático es un cáncer agresivo de células epiteliales de los conductos biliares intrahepáticos y su desarrollo se asocia a inflamación crónica del árbol biliar. En Chile, su epidemiología es limitada y el presente estudio tiene por objetivo describir su tasa de mortalidad. Métodos: se realizó un estudio descriptivo observacional transversal y ecológico de las defunciones por carcinoma de vías biliares en Chile durante 2017 y 2021 según sexo, grupo etario y región de residencia. Resultados: la tasa de mortalidad nacional de personas mayores a 20 años durante el periodo estudiado fue de 1,56 por cada 100.000 habitantes. La tasa de mortalidad más alta del sexo masculino se observó en 2020, siendo de 2,61. La mayor mortalidad se encontró en personas mayores a 80 años en el sexo masculino con una tasa de 24,38. A nivel regional, en Magallanes se observó la mayor tasa de mortalidad con 5,66, mientras que Tarapacá presentó la menor tasa con un valor de 0,96. Finalmente, el índice de Swaroop fue igual o mayor al 92% en todas las regiones del país. Conclusión: la mayor mortalidad por colangiocarcinoma intrahepático se presenta en personas de edad avanzada y de sexo masculino. Interesantemente la mayor mortalidad por esta causa se concentra en la zona sur de Chile. Dada la magnitud del problema que representa esta enfermedad en la salud pública nacional es que futuros estudios son necesarios para establecer medidas de prevención y/o tratamiento de esta enfermedad.

Introduction: intrahepatic cholangiocarcinoma is an aggressive cancer of epithelial cells of the intrahepatic bile ducts, and its deve-lopment is associated with chronic inflammation of the biliary tree. In Chile, its epidemiology is limited, and the present study aims to describe its mortality rate. Methods: a descriptive, cross-sectional, observational, and ecological study of deaths from bile duct carcinoma in Chile between 2017 and 2021 was performed according to sex, age group, and region of residence. Results: the national mortality rate of people over 20 years old during the study period was 1.56 per 100,000 inhabitants. The highest mortality rate for the male sex was observed in 2020, with a value of 2.61. In turn, the highest mortality rate was found in people over 80 years old in the male sex, with a rate value of 24.38. On a regional level, Magallanes had the highest mortality rate, with a rate value of 5.66, while Tarapacá had the lowest rate, with a value of 0.96. Finally, Swaroop's index was equal to or greater than 92% in all regions of the country. Conclusion: the highest mortality from intrahepatic cholangiocarcinoma occurs in older people and males. Interestingly, the highest mortality from this cause is concentrated in the southern zone of Chile. Given the magnitude of the problem that this disease represents for national public health, future studies are necessary to establish both prevention measures and treatments

Modelos pré-clínicos de câncer hepático / Preclinical models of liver câncer

ABSTRACT Background: This manuscript provides an overview of liver carcinogenesis in murine models of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Objective: A review through MEDLINE and EMBASE was performed to assess articles until August 2022. Methods: Search was conducted of the entire electronic databases and the keywords used was HCC, CCA, carcinogenesis, animal models and liver. Articles exclusion was based on the lack of close relation to the subject. Carcinogenesis models of HCC include HCC induced by senescence in transgenic animals, HCC diet-induced, HCC induced by chemotoxicagents, xenograft, oncogenes, and HCC in transgenic animals inoculated with B and C virus. The models of CCA include the use of dimethylnitrosamine (DMN), diethylnitrosamine (DEN), thioacetamide (TAA), and carbon tetrachloride (CCl4). CCA murine models may also be induced by: CCA cells, genetic manipulation, Smad4, PTEN and p53 knockout, xenograft, and DEN-left median bile duct ligation. Results: In this review, we described different murine models of carcinogenesis that reproduce the key points for HCC and CCA genesis allowing a better understanding of its genetic, physiopathological, and environmental abnormalities. Conclusion: Each model has its advantages, disadvantages, similarities, and differences with the corresponding human disease and should be chosen according to the specificity of the study. Ultimately, those models can also be used for testing new anticancer therapeutic approaches.

RESUMO Contexto: Este manuscrito fornece uma visão geral da carcinogênese hepática em modelos murinos de carcinoma hepatocelular (CHC) e colangiocarcinoma (CCA). Objetivo: Realizar uma revisão de artigos científicos até agosto de 2022 utilizando as bases de dados MEDLINE e EMBASE. Métodos: A busca foi realizada em todas as bases de dados eletrônicas e as palavras-chave usadas foram CHC, CCA, carcinogenesis, modelos animais e fígado. A exclusão dos artigos baseou-se na falta de estreita relação com o assunto. Os modelos de carcinogênese do CHC incluíram: CHC induzido por senescência em animais transgênicos, CHC induzido por dieta, CHC induzido por agentes quimiotóxicos, xenoenxerto, oncogenes e CHC em animais transgênicos inoculados com vírus B e C. Os modelos de CCA incluíram: o uso de dimetilnitrosamina (DMN), dietilnitrosamina (DEN), tioacetamida (TAA) e tetracloreto de carbono (CCl4). Os modelos murinos de CCA induzidos por incluir: células de CCA, manipulação genética, animais nocaute para Smad4, PTEN e p53, xenoenxerto e ligadura do ducto biliar mediano esquerdo. Resultados: Nesta revisão, descrevemos diferentes modelos murinos de carcinogênese que reproduzem os pontos-chave para a gênese do CHC e do CCA, permitindo uma melhor compreensão de suas anormalidades genéticas, fisiopatológicas e ambientais. Conclusão: Cada modelo tem suas vantagens, desvantagens, semelhanças e diferenças com a doença humana correspondente e deve ser escolhido de acordo com a especificidade do estudo. Em última análise, esses modelos também podem ser utilizados para testar novas abordagens terapêuticas anticancerígenas.

Proliferações biliares intra-hepáticas: histopatologia e potenciais marcadores imuno-histoquímicos / Intrahepatic biliary proliferations: histopathology and potential immunohistochemical markers

ABSTRACT Intrahepatic biliary proliferations represent a spectrum from reactive (ductular reaction, some with atypical architecture), hamartomatous (von Meyenburg complex), benign (bile duct adenoma) and precursor/borderline entities (biliary intraepithelial neoplasia, intraductal papillary neoplasm of the bile duct) to fully malignant (cholangiocarcinoma) neoplasms. Clinical pictures and even imaging patterns may be similar, requiring refined studies aiming at histopathological and immunohistochemistry for more precise diagnosis, essential for correct patient management. This article discusses updated concepts and definitions of most relevant entities aiming more specifically at the differential diagnosis in practice, focusing on morphology and immunohistochemistry, with a discussion of potential markers to help distinguishing between benign and malignant lesions.

RESUMO As proliferações biliares intra-hepáticas representam um espectro que abrange desde entidades reativas (reação ductular, algumas com arquitetura atípica), hamartomatosas (complexo de von Meyenburg), benignas (adenoma de ductos biliares) e precursoras/limítrofes (neoplasia intraepitelial biliar, neoplasia papilar intraductal de ducto biliar) até neoplasias totalmente malignas (colangiocarcinoma). Os quadros clínicos e até mesmo os padrões de imagem podem ser semelhantes, exigindo estudos refinados visando critério histológicos e imuno-histoquímicos para diagnósticos mais precisos, essenciais para o correto manejo do paciente. Este artigo discute conceitos atualizados e definições das entidades mais relevantes visando mais especificamente ao diagnóstico diferencial na prática, com foco na morfologia e imuno-histoquímica, com discussão de potenciais marcadores para ajudar na distinção entre lesões benignas e malignas.

Manejo de los tumores periampulares malignos en pacientes evaluados en consulta multidisciplinaria

Introducción: Los tumores malignos ubicados en la región periampular pueden ser: ampular (carcinoma ampular), biliar (colangiocarcinoma), pancreático (tumores de la cabeza del páncreas) o duodenal (cáncer de la segunda porción duodenal), y constituyen un problema de salud por su alta mortalidad, y un motivo frecuente de consulta multidisciplinaria por oncología digestiva. Objetivo: Describir los procederes diagnósticos y resultados histopatológicos asociados al manejo de tumores periampulares en pacientes atendidos en consulta multidisciplinaria. Materiales y métodos: Se realizó un estudio descriptivo y prospectivo en 34 pacientes con diagnóstico de estas neoplasias, en el Hospital Universitario Clínico Quirúrgico Comandante Faustino Pérez Hernández. La fecha comprende de enero a diciembre del año 2021. Se estudiaron variables como: grupos de edad, sexo, resultados imagenológicos, endoscópicos e histológicos, vía para la realización de la biopsia y tratamiento definitivo. Los resultados fueron recogidos en una planilla de recolección de datos. Resultados: Predominaron el sexo masculino y el grupo de 50 a 69 años. La tomografía axial computarizada abdominal mostró mayor sensibilidad en el diagnóstico respecto al ultrasonido. La colangiopancreatografía endoscópica retrograda fue el método diagnóstico y terapéutico más utilizado, seguido del tratamiento quirúrgico paliativo. Conclusiones: El manejo de los tumores, al igual que su tratamiento definitivo, estuvo relacionado con su localización. Como todos no pudieron ser estadificados, fue necesario el estudio histológico.

Introduction: Malignant tumors located in the periampullary region may be: ampullary (ampullary carcinoma), biliary (chollangiocarcinoma), pancreatic (tumors of the pancreas head) or duodenal (cancer of the second duodenal portion). They constitute a health problem due to their high mortality and a reason of frequent multidisciplinary consultation by digestive oncology. Objective: To describe the diagnostic procedures and the histopathological results associated to the management of periampullary tumors in patients treated in multidisciplinary consultations. Materials and methods: A descriptive and prospective study was conducted in 34 patients diagnosed with these neoplasms at the Clinical-Surgical University Hospital Comandante Faustino Perez. The date ranges from January to December 2021. Variables such as age groups, sex, imaging, endoscopic and histological results, pathway for biopsy and definitive treatment were studied. The results were collected in a data collection form. Results: Male sex and the age group from 50 to 69 years predominated. Abdominal computed axial tomography showed higher sensitivity in the diagnosis than ultrasound. Retrograde endoscopic cholangiopancreatography was the most widely used diagnostic and therapeutic method, followed by palliative surgical treatment Conclusions: The management of the tumors, as well as their definitive treatment, was related to their location. Since all of them could not be staged, histological study was necessary.

A Case Report of Primary Hepatic Tuberculosis

This case report presents an incidental finding of primary tuberculosis in the liver of a 54-year-old female patient who had a history of multiple hospital admissions due to abdominal pain, jaundice, persistent fever, nausea with vomiting, weight loss, and asthenia. The evaluation involved considering differential diagnoses of cholangiocarcinoma, Caroli's disease, hepatocellular carcinoma, and hepatic tuberculosis based on the patient's history, imaging studies, and laboratory tests. The aim of this report is to provide healthcare professionals with a new diagnostic perspective when encountering patients with this ambiguous presentation, even in regions with low epidemiological incidence. Hepatic tuberculosis should be included in the differential diagnosis of patients with focal intrahepatic lesions or liver abscesses who have a history of recurrent hospitalizations and evidence on imaging studies.

Se trata de un hallazgo incidental de tuberculosis primaria en el hígado en una paciente femenina de 54 años con historia de múltiples ingresos por síntomas de dolor abdominal, ictericia, fiebre persistente, náuseas acompañadas de vómitos de contenido gástrico, pérdida de peso y astenia. A la evaluación se consideraron los diagnósticos diferenciales de colangiocarcinoma, enfermedad de Caroli, carcinoma hepatocelular y tuberculosis hepática, basados en anamnesis, estudios de imágenes y pruebas de gabinete. Este reporte de caso brinda una nueva perspectiva diagnóstica para el personal de salud que reciba pacientes con esta presentación ambigua, aun en el contexto de baja incidencia epidemiológica. La tuberculosis hepática debe ser considerada en el diagnóstico diferencial de pacientes con lesiones focales a nivel intrahepático o abscesos hepáticos con hospitalizaciones recurrentes y evidencia de imágenes.

Tratamiento quirúrgico del colangiocarcinoma extrahepático / Surgical Treatment of Extrahepatic Cholangiocarcinoma

Introducción: El colangiocarcinoma constituye la neoplasia de la vía biliar más frecuente, la cual es responsable de una alta morbimortalidad. Objetivo: Determinar la morbilidad y la mortalidad por colangiocarcinoma extrahepático en el Servicio de Cirugía del Hospital Universitario Manuel Ascunce Domenech. Métodos: Se realizó un estudio descriptivo, prospectivo y observacional de pacientes que ingresaron en el Servicio de Cirugía General con diagnóstico de colangiocarcinoma extrahepático entre septiembre de 2018 y enero del 2022. El universo estuvo conformado por 21 pacientes que cumplieron con los criterios de inclusión. Se utilizaron métodos estadísticos descriptivos y cálculos con valores porcentuales. Resultados: La mayor incidencia de los pacientes fueron del sexo masculino y blancos, con el 71,4 por ciento y el 85,7 por ciento respectivamente. Predominó el adenocarcinoma como variedad histológica con un 85,7 por ciento, así como el colangiocarcinoma proximal y la variante esclerosante de su clasificación. El 71,4 por ciento de los pacientes egresaron vivos y con una cirugía con finalidad curativa. Conclusiones: La mayoría de los pacientes fueron masculinos, de color blanco y de procedencia rural. Los hallazgos más frecuentes fueron la localización proximal y la variante esclerosante. A más de la mitad de los pacientes se les realizó procedimiento de Hess y Whipple con finalidad curativa. La fuga biliar, el adenocarcinoma como tipo histológico y el estado al egreso vivo prevaleció en todos los pacientes(AU)

Introduction: Cholangiocarcinoma is the most frequent biliary tract neoplasm responsible for high morbidity and mortality. Objective: To determine morbidity and mortality due to extrahepatic cholangiocarcinoma in the surgery service of Hospital Universitario Manuel Ascunce Domenech. Methods: A descriptive, prospective and observational study was carried out with patients admitted to the general surgery service with a diagnosis of extrahepatic cholangiocarcinoma between September 2018 and January 2022. The study universe consisted of 21 patients who met the inclusion criteria. Descriptive statistical methods and calculations with percentage values were used. Results: The highest incidence of patients were male and white-skinned, accounting for 71.4 percent and 85.7 percent, respectively. Adenocarcinoma predominated as histological variety, representing 85.7 percent, together with proximal cholangiocarcinoma and the sclerosing variant of its classification. 71.4 percent of the patients were discharged alive and after curative surgery. Conclusions: Most of the patients were male, white-skinned and from rural origin. The most frequent findings were a proximal location and the sclerosing variant. Over half the patients underwent Hess and Whipple procedure with curative purpose. Biliary leakage, adenocarcinoma as histologic type, and the condition of alive at discharge prevailed in all patients(AU)

Mechanism Research Progress of Traditional Chinese Medicine in Prevention and Treatment of Cholangiocarcinoma / 肿瘤防治研究

Cholangiocarcinoma is a bile duct adenocarcinoma derived from the bile duct epithelium. Current treatment strategies for cholangiocarcinoma include surgery, chemotherapy, and radiotherapy. Surgical treatment is the first choice for all subtypes of cholangiocarcinoma. However, cholangiocarcinoma has the characteristics of high malignancy, easy recurrence after surgery, and low 5-year survival rates. Recent studies have found that many traditional Chinese medicines exhibit excellent anti-tumor effects in the treatment of various cancers, including cholangiocarcinoma. These medicines have advantages, such as low prices and abundant reserves, and are considered as an effective and safe complementary and alternative therapy for the treatment of cholangiocarcinoma. This article aims to review the effects of traditional Chinese medicine on cholangiocarcinoma from different aspects and levels in recent years. Results will provide new ideas for the prevention and treatment of cholangiocarcinoma.