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.

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.

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)

Inflammatory markers-based preoperative differentiation model of intrahepatic cholangiocarcinoma and combined hepatocellular carcinoma / 中华肝胆外科杂志

Objective:To establish and validate a preoperative differentiateon model of intrahepatic cholangiocarcinoma (ICC) and combined hepatocellular carcinoma (CHC) based on the inflammatory markers and conventional clinical indicators.Methods:The clinical data of 116 patients with ICC or CHC admitted to Henan Provincial People's Hospital from January 2018 to March 2023 were retrospectively analyzed, including 74 males and 42 females, aged (58.5±9.4) years old. The data of 83 patients were used to establish the differentiation model as the training group, including 50 cases of ICC and 33 cases of CHC. The data of 33 patients were used to validate the model as the validation group, including 20 cases of ICC and 13 cases of CHC. The clinical data including the platelet-to-lymphocyte ratio (PLR), systemic immune inflammation index (SII), prognostic inflammatory index (PII), prognostic nutritional index (PNI), neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) were collected and analyzed. The receiver operating characteristic (ROC) curve was used to analyze the best cut-off values of PLR, SII, PII, PNI, NLR and LMR. Univariate and multivariate logistic regression analysis were used to determine the differential factors between ICC and CHC. The R software was used to draw the nomogram, calculate the area under the curve (AUC) to evaluate the model accuracy, and draw the calibration chart and the decision curve to evaluate the predictive efficacy of the model.Results:Univariate logistic regression analysis showed that liver cirrhosis, history of hepatitis, alpha fetoprotein, carbohydrate antigen 199, gamma-glutamyltransferase (GGT), PLR, PNI and inflammation score (IS) could be used to differentiate ICC from CHC (all P<0.05). The indicators identified in univariate analysis were included in multivariate logistic regression analysis. The results showed that absence of liver cirrhosis, GGT>60 U/L, PNI>49.53, and IS<2 indicated the pathology of ICC (all P<0.05). Based on the above four factors, a nomogram model was established to differentiate the ICC and CHC. The AUC of ROC curve of the nomogram model in the training and validation groups were 0.851 (95% CI: 0.769-0.933) and 0.771 (95% CI: 0.594-0.949), respectively. The sensitivities were 0.760 and 0.750, and the specificities were 0.818 and 0.769, respectively. The calibration chart showed that the predicted curve fitted well to the reference line. The decision curve showed that the model has a clear positive net benefit. Conclusion:The nomogram model based on inflammatory markers showed a good differentiation performance of ICC and CHC, which could benefits the individualized treatment.

Construction and evaluation of a nomogram prediction model for survival after radical surgical resection of intrahepatic cholangiocarcinoma based on the albumin-bilirubin index / 中华肝胆外科杂志

Objective:To construct a nomogram prediction model for survival after radical surgical resection of intrahepatic cholangiocarcinoma (ICC) based on the albumin-bilirubin index (ALBI), and to evaluate its predictive efficacy.Methods:From January 2016 to January 2020, 170 patients with ICC who underwent radical surgical resection at the People's Hospital of Zhengzhou University were retrospectively analyzed. There were 90 males and 80 females, aged (58.5±10.6) years old. Based on a ratio of 7∶3 by the random number table, the patients were divided into the training set ( n=117) and the internal validation set ( n=53). The training set was used for nomogram model construction, and the validation set was used for model validation and evaluation. Follow up was conducted through outpatient reexamination and telephone contact. The Kaplan-Meier method was used for survival analysis, and a nomogram was drawn based on variables with a P<0.05 in multivariate Cox regression analysis. The predictive strength of the predictive model was evaluated by analyzing the consistency index (C-index), calibration curve, and clinical decision curve of the training and validation sets. Results:Multivariate Cox regression analysis showed that carbohydrate antigen 19-9 (CA19-9) ≥37 U/ml ( HR=1.99, 95% CI: 1.10-3.60, P=0.024), ALBI≥-2.80 ( HR=2.43, 95% CI: 1.40-4.22, P=0.002), vascular tumor thrombus ( HR=2.34, 95% CI: 1.40-3.92, P=0.001), and the 8th edition AJCC N1 staging ( HR=2.18, 95% CI: 1.21-3.95, P=0.010) were independent risk factors affecting postoperative survival of ICC patients after curative resection. The predictive model constructed based on the above variables was then evaluated, and the C-index of the model was 0.76. Calibration curve showed the predicted survival curve of ICC patients at 3 years after surgery based on the model was well-fitted to the 45° diagonal line which represented actual survival. Clinical decision curve analysis showed that the model had a significant positive net benefit in both the training and validation sets. Conclusion:The nomograph model for survival rate after radical resection of ICC was constructed based on four variables: ALBI, CA19-9, vascular tumor thrombus, and AJCC N staging (8th edition) in this study. This model provided a reference for more accurate prognosis evaluation and treatment selection plan for ICC patients.

Lymph node dissection for patients with intrahepatic cholangiocarcinoma in China: a meta-analysis / 中华肝胆外科杂志

Objective:To systematically review the profile of lymph node dissection (LND) for patients with intrahepatic cholangiocarcinoma (ICC) in China.Methods:Using the key words "intrahepatic cholangiocarcinoma" "intrahepatic cholangiocellular carcinoma" "lymph node dissection" "lymphadenec-tomy" "lymph node metastasis", the databases including China Zhiwang, Wanfang, Weipu, Sinomed, PubMed, Embase, Web of Science, Scopus, Cochrane Library were systematically searched. Cohort studies or randomized controlled clinical trials with intraoperative LND documentation and with analysis on the clinicopathologic characteristics or prognostic influences on patients with ICC were included into this meta-analysis from the date of database creation to April 20, 2022. The risk of bias in non-randomized controlled trials was evaluated using the Newcastle-Ottawa scale. A meta-analysis of preoperative imaging lymph node enlargement rates, LND rates, and pathological lymph node metastasis rates were performed using R software.Results:Thirty-three relevant studies that met the systematic evaluation criteria were included, all of which were retrospective cohort studies. All these publications were of medium to high quality. Patients’ enrollment ranged from 1993 to 2020. Patients were enrolled from 20 provinces/autonomous regions/municipalities with a total of 39 medical centers and 4 278 patients. The meta-analysis indicated that the LND rate, preoperative imaging lymph node enlargement rate, pathological lymph node metastasis rate were 47.8%(95% CI: 41.3%-54.3%), 18.5%(95% CI: 7.5%-29.6%) and 51.2%(95% CI: 43.8%-58.6%), respectively. Subgroup analysis showed the LND rate was 36.0%(95% CI: 27.0%-45.0%) in studies with a median year of enrollment before 2010, 48.3% (95% CI: 38.1%-58.6%) in studies from 2010 to 2017, and 53.3%(95% CI: 43.3%-63.2%) in studies after 2017. The LND rates were statistically different in the studies in the different periods of patient enrollment ( P=0.032). Conclusion:The meta-analysis indicated that the overall LND rate for ICC in China was not high but showed an increasing tendency.

Construction of a nomogram prediction model for survival after radical surgery for intrahepatic cholangiocarcinoma / 中华肝胆外科杂志

Objective:To study the factors influencing survival after radical resection in patients with intrahepatic cholangiocarcinoma (ICC), and to construct a nomogram on survival prediction.Methods:The clinical data of 139 patients with ICC who underwent radical resection at the People's Hospital of Zhengzhou University from June 2018 to December 2021 were retrospectively analyzed. There are 69 males and 70 females, aged (59.5±10.2) years old. These patients were divided into two groups based on a 3: 1 ratio by using the random number method: the test group ( n=104) and the validation group ( n=35). Data from the test group was used to construct a nomagram and data from the validation group was used to validate the predictive power of the nomagram. Univariate and multivariate Cox regression analyses were used to analyse factors influencing survival on the test group patients and to construct a nomogram. The predictive accuracy of the nomogram was determined by receiver operating characteristic (ROC) curves, concordance index (C-index) and calibration curves. Results:The results of the multivariate regression analysis showed that a combined hemoglobin, albumin, lymphocyte and platelet immunoinflammation (HALP) score <37.1 ( HR=1.784, 95% CI: 1.047-3.040), CA19-9 > 35U/ml ( HR=2.352, 95% CI: 1.139-4.857), poorly differentiated tumor ( HR=2.475, 95% CI: 1.237-4.953) and vascular invasion ( HR=1.897, 95% CI: 1.110-3.244) were independent risk factors that affected prognosis of patients with ICC after radical resection (all P<0.05). The AUCs of the nomogram in the test group in predicting the overall survival at 1, 2 and 3 years of patients with ICC after radical resection were 0.808, 0.853 and 0.859, respectively. There was good consistency between the prediction of the nomogram and actual observation. The predicted C-index of the total survival period of the test group was 0.765 (95% CI: 0.704-0.826), and the C-index of the validation group was 0.759 (95% CI: 0.673-0.845). Conclusion:A HALP score <37.1, CA19-9>35 U/ml, poorly differentiated tumour and vascular invasion were independent risk factors for prognosis of ICC patients after radical resection. The nomogram was established based on the above factors and showed good performance in predicting overall survival after radical resection in patients with ICC.

Efficacy and safety of radiotherapy combined with targeted therapy, immunotherapy and chemotherapy for unresectable intrahepatic cholangiocarcinoma / 中华放射医学与防护杂志

Objective:To evaluate the efficacy and safety of quadruple therapy involving radiotherapy (RT), lenvatinib, anti-PD-1 antibody and GEMOX (oxaliplatin and gemcitabine) chemotherapy (quadruple therapy) in treatment cohort of patients with unresectable intrahepatic cholangiocarcinoma (ICC).Methods:The patients with recurrent, metastatic, or unresectable ICC underwent quadruple therapy at Zhongshan Hospital, Fudan University between September 2018 and May 2022 were selected. The data about efficacy and safety of quadruple therapy were collected in the hospital electronic medical record system. All patients were followed up regularly to obtain the long-term prognostic data until December 31, 2022. The efficacy, prognosis, and toxicity data were collected and analyzed.Results:A total of 41 patients were included in the analysis. After a median follow-up period of 15 months, disease progression was diagnosed in 36 patients (18 patients died), while 3 patients were lost to follow-up. The causes of death included liver failure induced by intrahepatic tumor progression ( n=6), distant metastases (lungs or brain, n=6), abdominal lymph node metastases ( n=3), cancer cachexia ( n=2), and unknown cause ( n=1). The median progression-free survival (PFS) was 11 months (95% CI: 9.2-12.8), and the median overall survival (OS) was 35 months (95% CI: 17.0-52.0). All patients experienced treatment-related adverse events (AEs) during the study treatment period. Of the 41 patients, 13 patients experienced at least once grade 3 or worse treatment-related AE, but all were manageable with symptomatic treatment. No treatment-related deaths were reported during the follow-up period. Conclusions:Radiotherapy (RT), lenvatinib, anti-PD-1 antibody and GEMOX in the treatment of unresectable ICC shows significant efficacy and good safety, which is worthy of clinical application.

Prognostic Value of MRI Arterial-phase Enhancement Pattern in Intrahepatic Cholangiocarcinoma Patients / 中山大学学报(医学科学版)

ObjectiveTo investigate the prognostic value of the enhancement pattern in arterial phase of preoperative Gd-EOB-DTPA enhanced magnetic resonance imaging （MRI） in evaluating the disease-free survival （DFS） and overall survival （OS） in patients undergoing curative resection for intrahepatic cholangiocarcinoma （ICC）. MethodsA retrospective analysis was done on the clinical， preoperative MRI findings and postoperative follow-up results of 93 pathologically confirmed ICC patients undergoing surgery in our hospital between January 2018 and December 2021. Kaplan-Meier survival curves and log-rank test were used to compare the DFS and OS of three groups with different arterial enhancement patterns. Cox regression analysis was used to identify the factors affecting DFS and OS. ResultsThere were significant differences in DFS and OS among the 3 groups （log-rank test， P < 0.05）. The arterial enhancement pattern was an independent predictive factor for DFS （using diffuse hyperenhancement as a reference， peripheral rim enhancement： HR = 3.550； 95%CI： 1.16 ~ 10.8； P = 0.026；diffuse hypoenhancement： HR = 3.430； 95%CI： 1.04 ~ 11.3； P = 0.042）. The arterial enhancement pattern and tumor location were predictive factors for OS （（using diffuse hyperenhancement as a reference， diffuse hypoenhancement， HR = 8.500； 95%CI： 1.09-66.3； P = 0.041； using tumor distal location as a reference， tumor perihilar location HR=2.583，95%CI： 1.14-5.83， P =0.022）. The AUC of arterial enhancement patterns in predicting 1-， 2-， and 3- year DFS were 0.722， 0.748， and 0.617， respectively； in OS， 0.720， 0.704， and 0.730， respectively， which showed better prognostic efficacy than AJCC-TNM staging system. ConclusionArterial-phase enhancement pattern of preoperative Gd-EOB-DTPA enhanced MRI is an independent predictive factor for DFS and OS of ICC patients， with a better prognostic value than AJCC-TNM staging system， and can be used for the clinical management of ICC patients.

Efficacy and safety of microwave ablation combined with systemic chemotherapy in treatment of recurrent intrahepatic cholangiocarcinoma / 临床肝胆病杂志

Objective To investigate the efficacy and safety of microwave ablation (MWA) combined with chemotherapy versus MWA alone in the treatment of recurrent intrahepatic cholangiocarcinoma (RICC). Methods A retrospective cohort study was conducted among the patients with RICC who received MWA+chemotherapy or MWA in The Second People's Hospital of Neijiang and The Affiliated Hospital of Southwest Medical University from January 2014 to March 2021, and their clinicopathological data were collected. The independent samples t -test was used for comparison of continuous data, and the chi-square test and the Fisher's exact test were used for comparison of categorical data. The Kaplan-Meier method was used to calculate progression-free survival (PFS) and overall survival (OS), and the Log-rank test was used for comparison of survival differences. Univariate and multivariate Cox proportional-hazards regression model analyses were used to investigate the risk factors for survival and prognosis. Results A total of 106 patients with RIC were enrolled, among whom there were 55 patients in the MWA+chemotherapy group and 51 in the MWA group. By the end of follow-up, the MWA+chemotherapy group had a median PFS of 15.0 months (95% confidence interval [ CI ]: 14.5-15.5), and the MWA group had a median PFS of 13.4 months (95% CI : 11.6-15.2), with a significant difference between the two groups ( χ 2 =9.624, P =0.002). The MWA+chemotherapy group had a median OS of 21.0 months (95% CI : 20.0-21.8), and the MWA group had a median OS of 18.0 months (95% CI : 16.3-19.7), with a significant difference between the two groups ( χ 2 =12.784, P 5 cm, time to recurrence < 1 year, and absence of systemic chemotherapy tend to have a poor prognosis.

Influence of lymphadenectomy on efficacy of patients with intrahepatic cholangiocarcinoma at different locations / 中华消化外科杂志

Objective:To investigate the influence of lymphadenectomy on efficacy of patients with intrahepatic cholangiocarcinoma (ICC) at different locations.Methods:The retro-spective cohort study was conducted. The clinicopathological data of 123 patients with ICC who were admitted to the Affiliated Hospital of North Sichuan Medical College from January 2015 to January 2022 were collected. There were 78 males and 45 females, aged 55(rage, 50?60)years. All patients underwent radical resection. Observation indicators: (1) clinical characteristics of patients with ICC; (2) follow-up; (3) surgical situations in ICC patients with different number of lymph nodes dissected. Measurement data with normal distribution were represented as Mean± SD, and compari-son between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Kaplan-Meier method was used to draw survival curve and Log-Rank test was used for survival analysis. Results:(1) Clinical characteristics of patients with ICC. Of the 123 patients, 81 cases had peripheral ICC and 42 cases had central ICC. The albumin-bilirubin grade (grade 1, grade 2?3), preoperative lymph node metastasis risk assessment (low risk, high risk), the number of lymph nodes dissected (<6, ≥6), lymph node metastasis (positive, negative) were 57, 24, 51, 30, 49, 32, 15, 66 in patients with peripheral ICC, versus 19, 23, 17, 25, 14, 28, 16, 26 in patients with central ICC, showing significant differences in the above indicators between them ( χ2=7.40, 5.66, 8.17, 5.62, P<0.05). (2) Follow-up. All the 123 patients were followed up for 28(range, 21?38)months. The 3-year overall survival rate was 57.8% in the 81 patients with peripheral ICC, versus 32.3% in the 42 patients with central ICC, showing a significant difference between them ( χ2=5.98, P<0.05). Of the 42 patients with central ICC, there were 25 cases with high risk of lymph node metastasis before surgery and 17 cases with low risk of lymph node metastasis before surgery. Of the 25 central ICC patients with high risk of lymph node metastasis before surgery, the 3-year overall survival rate was 28.9% in the 18 cases with the number of lymph nodes dissected ≥6, versus 14.3% in the 7 cases with the number of lymph nodes dissected <6, showing a significant difference between them ( χ2=8.90, P<0.05). (3) Surgical situa-tions in patients with the different number of lymph nodes dissected. Of the 123 patients, cases with the number of lymph nodes dissected <6 and ≥6 were 63 and 60, and there was no significant difference in the operation time, intraoperative blood transfusion, postoperative complications, bile leakage, liver insufficiency, pulmonary infection, pleural effusion, abdominal effusion, or lymphatic leakage between them ( P>0.05). One patient might have multiple complications. Conclusions:The prognosis of patients with peripheral ICC is better than that of patients with central ICC. For patients with central ICC who are at high risk of lymph node metastasis before surgery, adequate lymph node dissection may result in a better prognosis.

Clinical effect of liver transplantation on hilar cholangiocarcinoma / 国际外科学杂志

Hilar cholangiocarcinoma(HCCA) is a relatively rare disease with great invasiveness. Traditionally, radical resection has been considered the cornerstone of its treatment. However, only less than 40% of cases can be resected. Surgical resection is complex, risky and difficult to achieve R0 resection and may lead to various postoperative complications. In recent years, the combination of neoadjuvant chemoradiotherapy with liver transplantation(LT) has provided an option for patients with unresectable diseases, and strict patient screening criteria has allowed LT protocol to achieve promising therapeutic effects in PCCA. In order to provide an intellectual background for the choice of LT protocol in the clinical treatment of HCCA patients, this article will review the application standards of LT in HCCA, summarize the application status of LT in patients with different resectability, compare the prognostic effect of resection and LT, and introduce the advantages of LT in the treatment of HCCA associated with primary sclerosing cholangitis(PSC).

Research progress and prospect of surgical treatment of intrahepatic cholangiocarcinoma in the era of liver transplantation / 国际外科学杂志

The incidence of intrahepatic cholangiocarcinoma has been increasing worldwide in recent years. Hepatectomy is the first choice for surgical treatment of intrahepatic cholangiocarcinoma. However, due to high tumor invasion, early lymph node metastasis and other factors, only less than 30% of cases are resectable, and the overall prognosis of patients is very poor. Theoretically, liver transplantation can not only remove the tumor, but also replace the damaged liver. Therefore, many scholars have proposed liver transplantation for the treatment of intrahepatic cholangiocarcinoma in order to obtain better results. Intrahepatic cholangiocarcinoma was once listed as a contraindication of liver transplantation due to limited cases, tumor recurrence, and shortage of donors. However, with the optimization of recipient screening criteria and the development of neoadjuvant therapy, part of patients can also benefit from it, making liver transplantation a potential therapeutic strategy. Based on the literature review and the author′s experience, this article introduced the current situation of surgical treatment of intrahepatic cholangiocarcinoma, the comparison between hepatectomy and liver transplantation, the latest progress of liver transplantation treatment and the future challenges and solutions.

Effect and Mechanism of Osthole on Proliferation and Apoptosis in Human Intrahepatic Cholangiocarcinoma HuCCT1 Cells / 中国实验方剂学杂志

ObjectiveTo investigate the effect and mechanism of osthole on the proliferation and apoptosis in human intrahepatic cholangiocarcinoma HuCCT1 cells. MethodThe effect of 10， 20， 40， 80， and 120 μmol·L-1 osthole on the proliferation of HuCCT1 cells was detected by the cell counting kit-8 （CCK-8）. A blank group， and low-， medium-， and high-dose osthole groups （16， 32， and 64 μmol·L-1） were set up. The effect of osthole on cell clone formation rate was detected by colony formation assay. The effect of osthole on cell cycle and apoptosis was detected by flow cytometry. The effect of osthole on cell apoptotic morphology was detected by Hoechst 33342 fluorescent staining. The effect of osthole on cell cycle protein cyclin B1， proliferating cell nuclear antigen （PCNA）， cysteine-aspartic acid protease （Caspase）-9， Caspase-3， cleaved Caspase-9， cleaved Caspase-3， cleaved poly（ADP-ribose） polymerase （cleaved PARP）， B-cell lymphoma-2 （Bcl-2）， phosphorylated protein kinase B （p-Akt）， phosphorylated mammalian target of rapamycin （p-mTOR）， and phosphorylated ribosomal protein S6 （p-RPS6） was detected by Western blot. ResultThe cell viability in the osthole group（40，80，120 μmol·L-1） decreased （P<0.05，P<0.01）， with the half maximal inhibitory concentration （IC50） of 63.8 μmol·L-1 as compared with that in the blank group. Compared with the blank group， the osthole groups（32，64 μmol·L-1）showed reduced clone formation rate （P<0.01）， increased number of cells in the G2 phase （P<0.05，P<0.01）， decreased number of cells， increased pyknosis and fragmentation， increased apoptosis rate （P<0.05，P<0.01）， down-regulated expression of cyclin B1， PCNA， Bcl-2， Caspase-3， Caspase-9， p-Akt， p-mTOR， and p-RPS6 （P<0.05，P<0.01）， and up-regulated expression of cleaved Caspase-3， cleaved Caspase-9， and cleaved PARP （P<0.05，P<0.01）. ConclusionOsthole can inhibit the proliferation and promote the apoptosis of HuCCT1 cells， and its mechanism may be related to the Akt/mTOR signaling pathway.

Effect of Photodynamic Therapy for Malignant Obstruction of Biliary Tract / 肿瘤防治研究

Objective To investigate the safety and efficacy of photodynamic therapy (PDT) for malignant obstruction of the biliary tract. Methods We retrospectively analyzed the clinical data of patients with malignant biliary obstruction treated by PDT in our medical center. On the basis of different treatment plans, the patients were categorized into the photodynamic only group and the combined treatment group, in which additional interventional operations, targeted therapy, or immunotherapy were arranged. The alterations in liver function, duration of biliary patency, and postoperative complications that occurred within one month were closely monitored in both groups. Results A total number of 19 patients were enrolled in this study. The technical success rate of PDT was 100%. The deterioration of liver function was not observed in any patients within one month after PDT. Within a maximum of 17.7 months follow-up, the patency rates of the biliary tract were 100.0%, 89.5%, 72%, and 64% at 1, 3, 6, and 12 months after the procedure, respectively. The mean biliary patency time was 6.9±0.8 months (95%CI: 5.2-8.7 months). Specifically, the biliary patency times for Bismuth type Ⅲ and Ⅳ were 7.5±1.1 and 6.1±1.3 months, respectively. The biliary patency time was around 3.3±0.7 months in the photodynamic only group and 7.9±0.9 months in the combined treatment group (P=0.017). Conclusion PDT for Bismuth Ⅲ-Ⅳ malignant biliary obstruction is safe and effective. Moreover, the period of biliary patency is greatly extended when PDT is combined with systemic therapy.