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1.
J Biochem Mol Toxicol ; 38(6): e23733, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38770938

RESUMEN

The aim of this investigation was to evaluate the differential expression of the sterol O-acyltransferase 1 (SOAT1) protein in gallbladder cancer tissues and cells, investigate the impact of Avastin on the proliferation, migration, invasion capabilities of gallbladder cancer cells, and its potential to induce cell apoptosis. Immunohistochemical analysis of samples from 145 gallbladder cancer patients was conducted, along with analysis of SOAT1 protein, mRNA expression levels, and cholesterol content in gallbladder cancer cell lines SGC-996, NOZ, and gallbladder cancer (GBC)-SD using Western blot and q-PCR techniques. Furthermore, the effects of Avastin on the proliferation, migration, and invasion capabilities of these gallbladder cancer cell lines were studied, and its ability to induce cell apoptosis was evaluated using flow cytometry, Western blot, and immunohistochemical methods. Additionally, gene expression and pathway analysis were performed, and the synergistic therapeutic effects of Avastin combined with gemcitabine were tested in a gallbladder cancer xenograft model. The study found that SOAT1 expression was significantly upregulated in GBC tissues and positively correlated with lymph node metastasis and TNM staging. In vitro experiments demonstrated that Avastin significantly inhibited the proliferation, migration, and invasion capabilities of SGC-996 and GBC-SD cell lines and induced apoptosis. RNA sequencing analysis revealed multiple differentially expressed genes in cells treated with Avastin, primarily enriched in biological pathways such as signaling transduction, malignant tumors, and the immune system. In vivo, experiments confirmed that Avastin could effectively suppress tumor growth in a gallbladder cancer xenograft model and enhanced the treatment efficacy when used in combination with gemcitabine. Overall, these findings provide new insights and strategies for targeted therapy in gallbladder cancer.


Asunto(s)
Neoplasias de la Vesícula Biliar , Esterol O-Aciltransferasa , Neoplasias de la Vesícula Biliar/patología , Neoplasias de la Vesícula Biliar/tratamiento farmacológico , Neoplasias de la Vesícula Biliar/metabolismo , Neoplasias de la Vesícula Biliar/genética , Humanos , Femenino , Masculino , Línea Celular Tumoral , Animales , Persona de Mediana Edad , Esterol O-Aciltransferasa/metabolismo , Esterol O-Aciltransferasa/genética , Ratones , Gemcitabina , Proliferación Celular/efectos de los fármacos , Anticuerpos Monoclonales Humanizados/farmacología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Ratones Desnudos , Apoptosis/efectos de los fármacos , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacología , Desoxicitidina/uso terapéutico , Movimiento Celular/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , Anciano , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Ratones Endogámicos BALB C , Proteínas de Neoplasias/metabolismo , Proteínas de Neoplasias/genética
2.
Hepatology ; 79(6): 1324-1336, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38758104

RESUMEN

BACKGROUND AND AIMS: Tea and coffee are widely consumed beverages worldwide. We evaluated their association with biliary tract cancer (BTC) incidence. APPROACH AND RESULTS: We pooled data from 15 studies in the Biliary Tract Cancers Pooling Project to evaluate associations between tea and coffee consumption and biliary tract cancer development. We categorized participants as nondrinkers (0 cup/day), moderate drinkers (>0 and <3 cups/day), and heavy drinkers (≥3 cups/day). We estimated multivariable HRs and 95% CIs using Cox models. During 29,911,744 person-years of follow-up, 851 gallbladder, 588 intrahepatic bile duct, 753 extrahepatic bile duct, and 458 ampulla of Vater cancer cases were diagnosed. Individuals who drank tea showed a statistically significantly lower incidence rate of gallbladder cancer (GBC) relative to tea nondrinkers (HR=0.77; 95% CI, 0.64-0.91), and intrahepatic bile duct cancer (IHBDC) had an inverse association (HR=0.81; 95% CI, 0.66-1.00). However, no associations were observed for extrahepatic bile duct cancer (EHBDC) or ampulla of Vater cancer (AVC). In contrast, coffee consumption was positively associated with GBC, with a higher incidence rate for individuals consuming more coffee (HR<3 cups/day =1.29; 95% CI, 1.01-1.66; HR≥3 cups/day =1.49; 95% CI, 1.11-1.99, Ptrend=0.01) relative to coffee nondrinkers. However, there was no association between coffee consumption and GBC when restricted to coffee drinkers. There was little evidence of associations between coffee consumption and other biliary tract cancers. CONCLUSIONS: Tea consumption was associated with a lower incidence of GBC and possibly IHBDC. Further research is warranted to replicate the observed positive association between coffee and GBC.


Asunto(s)
Neoplasias del Sistema Biliar , Café , , Humanos , Masculino , Femenino , Persona de Mediana Edad , Neoplasias del Sistema Biliar/epidemiología , Neoplasias del Sistema Biliar/etiología , Anciano , Incidencia , Neoplasias de la Vesícula Biliar/epidemiología , Neoplasias de la Vesícula Biliar/etiología , Neoplasias de la Vesícula Biliar/prevención & control , Factores de Riesgo , Adulto , Neoplasias de los Conductos Biliares/epidemiología , Neoplasias de los Conductos Biliares/etiología
3.
Medicine (Baltimore) ; 103(18): e37880, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38701302

RESUMEN

INTRODUCTION: Incidental gallbladder carcinoma refers to a discovery of gallbladder cancer during or after cholecystectomy. Late port-site metastasis (PSM) following Laparoscopic cholecystectomy (LC) is rare with an incidence rate of 10.3%. PATIENT CONCERNS: We report a case of a 58-year-old man who presented with a painful abdominal wall mass for 6 weeks. He had a history of LC for symptomatic cholelithiasis, 8 years prior. DIAGNOSIS: Histopathological examination revealed a positive result for metastatic adenocarcinoma from the abdominal wall mass. Moreover, Positron emission tomography (PET) showed a small focus of intense fluorodeoxyglucose (FDG) uptake in the gallbladder bed, which was highly suspicious for malignancy. INTERVENTION: Decision was to proceed with surgery owing to uptake in the gallbladder bed with single-site metastasis to the previous port site. In addition, in the board meeting, an agreement was reached for performing distal pancreatectomy with splenectomy owing to uncertainty of malignancy based on what was discovered during the full metastatic workup. Diagnostic laparoscopy followed by midline laparotomy performed. Radical completion cholecystectomy with lymphadenectomy was done. Followed by complete resection of the anterior abdominal wall. Distal pancreatectomy and splenectomy were then performed. OUTCOME: Pathological diagnosis showed metastatic/invasive, moderately differentiated adenocarcinoma with positive margins on the posterior surface of excised port-site mass. The positive margins necessitated further chemoradiotherapy, followed by adjuvant chemotherapy until lung metastasis was identified. After this, the patient was scheduled for palliative chemotherapy. CONCLUSION: Presence of PSM is often associated with peritoneal metastasis. For this reason, it is advised to evaluate the patient for possible metastasis.


Asunto(s)
Adenocarcinoma , Colecistectomía Laparoscópica , Neoplasias de la Vesícula Biliar , Humanos , Neoplasias de la Vesícula Biliar/patología , Neoplasias de la Vesícula Biliar/secundario , Neoplasias de la Vesícula Biliar/cirugía , Colecistectomía Laparoscópica/efectos adversos , Masculino , Persona de Mediana Edad , Adenocarcinoma/secundario , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Siembra Neoplásica , Pared Abdominal/patología , Hallazgos Incidentales
4.
Front Cell Infect Microbiol ; 14: 1374238, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38774627

RESUMEN

Gallbladder cancer (GBC) is the most common malignant tumor of the biliary system with the worst prognosis. Even after radical surgery, the majority of patients with GBC have difficulty achieving a clinical cure. The risk of tumor recurrence remains more than 65%, and the overall 5-year survival rate is less than 5%. The gut microbiota refers to a variety of microorganisms living in the human intestine, including bacteria, viruses and fungi, which profoundly affect the host state of general health, disease and even cancer. Over the past few decades, substantial evidence has supported that gut microbiota plays a critical role in promoting the progression of GBC. In this review, we summarize the functions, molecular mechanisms and recent advances of the intestinal microbiota in GBC. We focus on the driving role of bacteria in pivotal pathways, such as virulence factors, metabolites derived from intestinal bacteria, chronic inflammatory responses and ecological niche remodeling. Additionally, we emphasize the high level of correlation between viruses and fungi, especially EBV and Candida spp., with GBC. In general, this review not only provides a solid theoretical basis for the close relationship between gut microbiota and GBC but also highlights more potential research directions for further research in the future.


Asunto(s)
Bacterias , Neoplasias de la Vesícula Biliar , Microbioma Gastrointestinal , Humanos , Neoplasias de la Vesícula Biliar/microbiología , Bacterias/clasificación , Bacterias/aislamiento & purificación , Animales , Disbiosis/microbiología , Factores de Virulencia , Hongos/patogenicidad , Hongos/clasificación
5.
Cancer Lett ; 592: 216923, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38697462

RESUMEN

Liver metastasis is common in patients with gallbladder cancer (GBC), imposing a significant challenge in clinical management and serving as a poor prognostic indicator. However, the mechanisms underlying liver metastasis remain largely unknown. Here, we report a crucial role of tyrosine aminotransferase (TAT) in liver metastasis of GBC. TAT is frequently up-regulated in GBC tissues. Increased TAT expression is associated with frequent liver metastasis and poor prognosis of GBC patients. Overexpression of TAT promotes GBC cell migration and invasion in vitro, as well as liver metastasis in vivo. TAT knockdown has the opposite effects. Intriguingly, TAT promotes liver metastasis of GBC by potentiating cardiolipin-dependent mitophagy. Mechanistically, TAT directly binds to cardiolipin and leads to cardiolipin externalization and subsequent mitophagy. Moreover, TRIM21 (Tripartite Motif Containing 21), an E3 ubiquitin ligase, interacts with TAT. The histine residues 336 and 338 at TRIM21 are essential for this binding. TRIM21 preferentially adds the lysine 63 (K63)-linked ubiquitin chains on TAT principally at K136. TRIM21-mediated TAT ubiquitination impairs its dimerization and mitochondrial location, subsequently inhibiting tumor invasion and migration of GBC cells. Therefore, our study identifies TAT as a novel driver of GBC liver metastasis, emphasizing its potential as a therapeutic target.


Asunto(s)
Movimiento Celular , Neoplasias de la Vesícula Biliar , Neoplasias Hepáticas , Ribonucleoproteínas , Ubiquitinación , Humanos , Neoplasias de la Vesícula Biliar/patología , Neoplasias de la Vesícula Biliar/genética , Neoplasias de la Vesícula Biliar/metabolismo , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Animales , Línea Celular Tumoral , Masculino , Ribonucleoproteínas/metabolismo , Ribonucleoproteínas/genética , Femenino , Mitofagia , Invasividad Neoplásica , Ratones , Ratones Desnudos , Persona de Mediana Edad , Regulación Neoplásica de la Expresión Génica , Ratones Endogámicos BALB C
6.
BMC Cancer ; 24(1): 597, 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38755562

RESUMEN

BACKGROUND: With the increasing of novel therapeutics for the treatment of Biliary Tract Cancers (BTC), and the need to assess their socio-economic impacts for national licence approvals, it is as important as ever to have real-life data in national populations. METHODS AND RESULTS: We performed an audit of the first 2 year-activity (Sep 2019-Sep 2021) of the centralized West-of-Scotland-BTC clinic. 122 patients accessed the service, including 68% with cholangiocarcinoma (CCA), 27% with gallbladder cancer (GBC), and 5% with ampulla of Vater carcinoma with biliary phenotype (AVC). Median age at diagnosis was 66 (28-84), with 30% of newly diagnosed patients being younger than 60 years-old. Thirty-five cases (29%) underwent surgery, followed by adjuvant-chemotherapy in 66%. 60% had recurrent disease (80% with distant relapse). Sixty-four patients (58%) started first-line Systemic-AntiCancer-Treatment (SACT). Of these, 37% received second line SACT, the majority of which had iCCA and GBC. Thirty-% of those who progressed received third line SACT. CONCLUSIONS: About 30% of BTC were eligible for curative surgery. Fifty-eight and twenty% of the overall cohort of advanced BTC patients received first and second line SACT. Our data suggest that reflex genomic profiling may not be cost-effective until molecularly driven strategies are limited to second line setting.


Asunto(s)
Neoplasias del Sistema Biliar , Humanos , Persona de Mediana Edad , Femenino , Masculino , Anciano , Adulto , Escocia/epidemiología , Anciano de 80 o más Años , Neoplasias del Sistema Biliar/terapia , Neoplasias del Sistema Biliar/epidemiología , Colangiocarcinoma/terapia , Colangiocarcinoma/patología , Neoplasias de la Vesícula Biliar/terapia , Neoplasias de la Vesícula Biliar/patología , Neoplasias de la Vesícula Biliar/epidemiología , Quimioterapia Adyuvante
7.
J Med Ultrason (2001) ; 51(2): 227-233, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38700561

RESUMEN

Endoscopic ultrasonography (EUS) provides high spatial resolution and more detailed images than other diagnostic modalities. Furthermore, EUS-guided tissue acquisition (EUS-TA), such as EUS-guided fine needle aspiration or biopsy (EUS-FNA/FNB), is an indispensable tool in pancreaticobiliary disease diagnostics, supporting a conclusive pathological diagnosis. In this review, we evaluate the current status and the usefulness of EUS-TA for the diagnostics of the following biliary tract diseases: (A) biliary stricture diagnostics, (B) biliary tract cancer (BTC) itself, and (C) staging of advanced BTC. Previous reports have shown that EUS-FNA for biliary lesions is a safe procedure that is useful in differentiating biliary cancer from benign lesions and in the staging of BTC. On the other hand, the diagnostic performance of EUS-TA for bile duct lesions is reported to be similar to that of transpapillary biopsy. Overall, EUS-TA for biliary lesions may be a safe and effective method, but it should be performed with an understanding of the risk of serious adverse events such as bile leakage and peritoneal dissemination of cancer. It is recommended for distal biliary stricture lesions for which endoscopic retrograde cholangiopancreatography cannot confirm the diagnosis or gallbladder lesions if they do not require the needle to pass through the biliary lumen.


Asunto(s)
Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico , Humanos , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico/métodos , Endosonografía/métodos , Constricción Patológica/diagnóstico por imagen , Neoplasias de la Vesícula Biliar/diagnóstico por imagen , Neoplasias de la Vesícula Biliar/patología , Vesícula Biliar/diagnóstico por imagen , Vesícula Biliar/patología , Enfermedades de las Vías Biliares/diagnóstico por imagen , Neoplasias del Sistema Biliar/diagnóstico por imagen , Neoplasias del Sistema Biliar/patología
9.
Rev. colomb. cir ; 39(3): 441-448, 2024-04-24. tab
Artículo en Español | LILACS | ID: biblio-1554115

RESUMEN

Introducción. El cáncer de vesícula biliar es el más común en el tracto biliopancreático y una importante causa de mortalidad. La metaplasia y la displasia han sido mencionados como probables precursores relacionados con la secuencia metaplasia-displasia-cáncer. El objetivo de este estudio fue establecer las posibles asociaciones entre estas alteraciones histopatológicas y su relación con la edad y el sexo de los pacientes. Métodos. Estudio observacional retrospectivo descriptivo, con un componente analítico de corte transversal. Se incluyeron los informes de patología de pacientes llevados a colecistectomía laparoscópica electiva y ambulatoria, entre enero de 2015 y diciembre de 2020, con colecistitis crónica, colelitiasis o pólipos vesiculares, mayores de 18 años. Se describieron las características demográficas por sexo y edad utilizando medias, desviaciones estándar y porcentajes. Se emplearon la prueba de chi cuadrado y la prueba exacta de Fisher para evaluar la asociación entre las variables cualitativas. Resultados. Se incluyeron 4871 informes de patología. En esta cohorte se encontró asociación estadísticamente significativa entre metaplasia, displasia y cáncer de vesícula (p<0,05), al igual que con el sexo y la edad de los pacientes. Conclusiones. Los resultados sugieren una asociación entre metaplasia, displasia y cáncer de vesícula biliar en la población estudiada. Se recomienda la realización de investigaciones complementarias para definir la posible causalidad entre metaplasia, displasia y cáncer de vesícula biliar en una población más heterogénea.


Introduction. Gallbladder cancer is the most common cancer in the biliopancreatic tract and an important cause of mortality. Metaplasia and dysplasia have been mentioned as probable precursors related to the metaplasia-dysplasia-cancer sequence. The objective of this study was to establish the possible associations between these histopathological alterations and their relationship with the age and sex of the patients. Methods. Descriptive retrospective observational study, with a cross-sectional analytical component. Pathology reports of patients undergoing elective and outpatient laparoscopic cholecystectomy were included between January 2015 and December 2020, with chronic cholecystitis, cholelithiasis, or gallbladder polyps, over 18 years of age. Demographic characteristics by sex and age was performed using means, standard deviations, and percentages. The chi2 test and Fisher's exact test were used to evaluate the association between the qualitative variables. Results. 4871 pathology reports were included. In this cohort, a statistically significant association was found between metaplasia, dysplasia, and gallbladder cancer (p<0.05), as well as with the sex and age of the patients. Conclusions. The results suggest an association between metaplasia, dysplasia and gallbladder cancer in the study population. Additional research is recommended to define the possible causality between metaplasia, dysplasia, and gallbladder cancer in a more heterogeneous population.


Asunto(s)
Humanos , Colecistectomía , Neoplasias de la Vesícula Biliar , Progresión de la Enfermedad , Vesícula Biliar , Metaplasia , Neoplasias
10.
Int J Med Sci ; 21(5): 862-873, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38617005

RESUMEN

Background: Direct liver invasion (DI) is a predominant pathway of gallbladder cancer (GBC) metastasis, but the molecular alterations associated with DI remain addressed. This study identified specific genes correlated with DI, which may offer a potential biomarker for the diagnosis and prognosis of advanced GBC. Methods: RNA samples from 3 patients with DI of GBC were used for RNA-seq analysis. Differentially expressed genes and metabolic pathways between primary tumor (T) and DI tissue was used to analyze aberrant gene expressions. Immunohistochemistry (IHC) of fatty acid binding protein 1 (FABP1) in 62 patients with DI was engaged to evaluate its association with clinicopathological characteristics and prognosis. IHC of CD3+ and CD8+ T cells was analyzed for their correlation with FABP1 expression, clinicopathological features and prognosis. Univariate and multivariate Cox hazards regression analyses were performed to identify independent prognostic factors for disease-free survival (DFS) and overall survival (OS). Results: FABP1 mRNA levels were significantly upregulated in DI region compared to T tissue. IHC results showed identical results with elevated FABP1 (p < 0.0001). Expression of FABP1 in DI region was significantly associated with lymph node metastasis (P = 0.028), reduced DFS (P = 0.013) and OS (P = 0.022); in contrast, its expression in T region was not associated with clinicopathological characteristics and prognosis (P > 0.05). The density of CD8+ T cells in DI region with higher FABP1 expression was significantly lower than that with lower FABP1 expression (p = 0.0084). Multivariate analysis unveiled those hepatic metastatic nodules (HR = 3.35, 95%CI: 1.37-8.15, P = 0.008) and FABP1 expression in DI region (HR = 2.01, 95%CI: 1.05-3.88, P = 0.036) were high risk factors for OS, and FABP1(HR = 2.05, 95%CI: 1.04-4.06, P = 0.039) was also a high risk factor for DFS. Conclusions: Elevated expression of FABP1 in DI region serves as a potential prognostic biomarker for advanced GBC with DI.


Asunto(s)
Carcinoma in Situ , Carcinoma , Neoplasias de la Vesícula Biliar , Humanos , Linfocitos T CD8-positivos , Proteínas de Unión a Ácidos Grasos/genética , Neoplasias de la Vesícula Biliar/genética , Hígado , Pronóstico
11.
Zhonghua Wai Ke Za Zhi ; 62(4): 265-272, 2024 Apr 01.
Artículo en Chino | MEDLINE | ID: mdl-38582611

RESUMEN

The incidence of gallbladder cancer has been increasing. Radial resection is still the most promising curable treatment for patients with gallbladder cancer. Although the techniques required for laparoscopic radical resection of gallbladder cancer have matured, the number of reports is also on the rise, and laparoscopic radical resection of gallbladder cancer is still controversial. To standardize laparoscopic radical resection of gallbladder cancer, the Biliary Surgery Branch, Chinese Society of Surgery, Chinese Medical Association, together with the Chinese Medical Doctor Association in Chinese Committee of Biliary Surgeons, gathered experts to formulate recommendations and consensus on laparoscopic radical resection of gallbladder cancer. This consensus includes several parts: safety, preoperative evaluation, indications, surgical team, positioning of patient and trocars, intraoperative frozen examination, lymph node dissection, liver resection,bile duct resection, etc. Furthermore, suggestions on the principle of treatment, surgical procedures, and precautions were also provided for patients with delayed diagnoses of gallbladder cancer undergoing resection. This consensus aims to offer valuable suggestions for the standardization of laparoscopic radical resection of gallbladder cancer.


Asunto(s)
Colecistectomía Laparoscópica , Neoplasias de la Vesícula Biliar , Laparoscopía , Humanos , Neoplasias de la Vesícula Biliar/diagnóstico , Consenso , Colecistectomía/métodos , Conductos Biliares/patología , Colecistectomía Laparoscópica/efectos adversos , Colecistectomía Laparoscópica/métodos
13.
Acta Med Okayama ; 78(2): 201-204, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38688839

RESUMEN

Trousseau syndrome is characterized by cancer-associated systemic thrombosis. We describe the first case of a successfully treated gallbladder adenocarcinoma accompanied by Trousseau syndrome. A 66-year-old woman presented with right hemiplegia. Magnetic resonance imaging identified multiple cerebral infarctions. Her serum carbohydrate antigen 19-9 and D-dimer levels were markedly elevated, and a gallbladder tumor was detected via abdominal computed tomography. Venous ultrasonography of the lower limbs revealed a deep venous thrombus in the right peroneal vein. These findings suggested that the brain infarctions were likely caused by Trousseau syndrome associated with her gallbladder cancer. Radical resection of the gallbladder tumor was performed. The resected gallbladder was filled with mucus and was pathologically diagnosed as an adenocarcinoma. Her postoperative course was uneventful, and she received a one-year course of adjuvant therapy with oral S-1. No cancer recurrence or thrombosis was noted 26 months postoperatively. Despite concurrent Trousseau syndrome, a radical cure of the primary tumor and thrombosis could be achieved with the appropriate treatment.


Asunto(s)
Adenocarcinoma , Neoplasias de la Vesícula Biliar , Humanos , Neoplasias de la Vesícula Biliar/cirugía , Neoplasias de la Vesícula Biliar/complicaciones , Femenino , Anciano , Adenocarcinoma/cirugía , Adenocarcinoma/complicaciones , Trombosis de la Vena/cirugía , Trombosis de la Vena/diagnóstico por imagen , Síndrome , Infarto Cerebral/cirugía , Infarto Cerebral/diagnóstico por imagen , Infarto Cerebral/etiología
14.
Acta Radiol ; 65(6): 554-564, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38623640

RESUMEN

BACKGROUND: Computed tomography (CT) radiomics combined with deep transfer learning was used to identify cholesterol and adenomatous gallbladder polyps that have not been well evaluated before surgery. PURPOSE: To investigate the potential of various machine learning models, incorporating radiomics and deep transfer learning, in predicting the nature of cholesterol and adenomatous gallbladder polyps. MATERIAL AND METHODS: A retrospective analysis was conducted on clinical and imaging data from 100 patients with cholesterol or adenomatous polyps confirmed by surgery and pathology at our hospital between September 2015 and February 2023. Preoperative contrast-enhanced CT radiomics combined with deep learning features were utilized, and t-tests and least absolute shrinkage and selection operator (LASSO) cross-validation were employed for feature selection. Subsequently, 11 machine learning algorithms were utilized to construct prediction models, and the area under the ROC curve (AUC), accuracy, and F1 measure were used to assess model performance, which was validated in a validation group. RESULTS: The Logistic algorithm demonstrated the most effective prediction in identifying polyp properties based on 10 radiomics combined with deep learning features, achieving the highest AUC (0.85 in the validation group, 95% confidence interval = 0.68-1.0). In addition, the accuracy (0.83 in the validation group) and F1 measure (0.76 in the validation group) also indicated strong performance. CONCLUSION: The machine learning radiomics combined with deep learning model based on enhanced CT proves valuable in predicting the characteristics of cholesterol and adenomatous gallbladder polyps. This approach provides a more reliable basis for preoperative diagnosis and treatment of these conditions.


Asunto(s)
Aprendizaje Profundo , Tomografía Computarizada por Rayos X , Humanos , Femenino , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , Tomografía Computarizada por Rayos X/métodos , Anciano , Vesícula Biliar/diagnóstico por imagen , Neoplasias de la Vesícula Biliar/diagnóstico por imagen , Adulto , Pólipos/diagnóstico por imagen , Colesterol , Enfermedades de la Vesícula Biliar/diagnóstico por imagen , Valor Predictivo de las Pruebas , Pólipos Adenomatosos/diagnóstico por imagen , Aprendizaje Automático , Medios de Contraste , Radiómica
15.
Acta Radiol ; 65(5): 422-431, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38584372

RESUMEN

BACKGROUND: Gallbladder cancer is a rare but aggressive malignancy that is often diagnosed at an advanced stage and is associated with poor outcomes. PURPOSE: To develop a radiomics model to discriminate between benign and malignant gallbladder lesions using enhanced computed tomography (CT) imaging. MATERIAL AND METHODS: All patients had a preoperative contrast-enhanced CT scan, which was independently analyzed by two radiologists. Regions of interest were manually delineated on portal venous phase images, and radiomics features were extracted. Feature selection was performed using mRMR and LASSO methods. The patients were randomly divided into training and test groups at a ratio of 7:3. Clinical and radiomics parameters were identified in the training group, three models were constructed, and the models' prediction accuracy and ability were evaluated using AUC and calibration curves. RESULTS: In the training group, the AUCs of the clinical model and radiomics model were 0.914 and 0.968, and that of the nomogram model was 0.980, respectively. There were statistically significant differences in diagnostic accuracy between nomograms and radiomics features (P <0.05). There was no significant difference in diagnostic accuracy between the nomograms and clinical features (P >0.05) or between the clinical features and radiomics features (P >0.05). In the testing group, the AUC of the clinical model and radiomics model were 0.904 and 0.941, and that of the nomogram model was 0.948, respectively. There was no significant difference in diagnostic accuracy between the three groups (P >0.05). CONCLUSION: It was suggested that radiomics analysis using enhanced CT imaging can effectively discriminate between benign and malignant gallbladder lesions.


Asunto(s)
Medios de Contraste , Neoplasias de la Vesícula Biliar , Vesícula Biliar , Tomografía Computarizada por Rayos X , Humanos , Masculino , Femenino , Neoplasias de la Vesícula Biliar/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Persona de Mediana Edad , Anciano , Diagnóstico Diferencial , Adulto , Vesícula Biliar/diagnóstico por imagen , Estudios Retrospectivos , Anciano de 80 o más Años , Nomogramas , Intensificación de Imagen Radiográfica/métodos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Radiómica
16.
J Cell Mol Med ; 28(9): e18328, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38683130

RESUMEN

Gallbladder cancer is a rare but fatal malignancy. However, the mechanisms underlying gallbladder carcinogenesis and its progression are poorly understood. The function of m6A modification and its regulators was still unclear for gallbladder cancer. The current study seeks to investigate the function of YTH m6A RNA-binding protein 1 (YTHDF1) in gallbladder cancer. Transcriptomic analysis and immunochemical staining of YTHDF1 in gallbladder cancer tissues revealed its upregulation compared to paracancerous tissues. Moreover, YTHDF1 promotes the proliferation assays, Transwell migration assays, and Transwell invasion assays of gallbladder cancer cells in vitro. And it also increased tumour growth in xenograft mouse model and metastases in tail vein injection model in vivo. In vitro, UHRF1 knockdown partly reversed the effects of YTHDF1 overexpression. Mechanistically, dual-luciferase assays proved that YTHDF1 promotes UHRF1 expression via direct binding to the mRNA 3'-UTR in a m6A-dependent manner. Overexpression of YTHDF1 enhanced UHRF1 mRNA stability, as demonstrated by mRNA stability assays, and Co-IP studies confirmed a direct interaction between YTHDF1 and PABPC1. Collectively, these findings provide new insights into the progression of gallbladder cancer as well as a novel post-transcriptional mechanism of YTHDF1 via stabilizing target mRNA.


Asunto(s)
Adenosina , Neoplasias de la Vesícula Biliar , Regulación Neoplásica de la Expresión Génica , Proteínas de Unión al ARN , Ubiquitina-Proteína Ligasas , Animales , Femenino , Humanos , Masculino , Ratones , Adenosina/análogos & derivados , Proteínas Potenciadoras de Unión a CCAAT/metabolismo , Proteínas Potenciadoras de Unión a CCAAT/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Progresión de la Enfermedad , Neoplasias de la Vesícula Biliar/genética , Neoplasias de la Vesícula Biliar/patología , Neoplasias de la Vesícula Biliar/metabolismo , Ratones Desnudos , Estabilidad del ARN/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética
17.
Hum Pathol ; 146: 86-94, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38615999

RESUMEN

AIMS: Significance of peribiliary capillary plexus (PCP) in gallbladder neoplasms remains unclear. Aims are to characterize high-grade biliary intraepithelial neoplasm (BilIN), pyloric gland adenoma (PGA), and intracholecystic papillary neoplasm (ICPN), precursors of gallbladder carcinoma, and to differentiate invasive carcinoma from pseudo-invasive lesions in gallbladder walls, referring to PCP. MATERIALS AND METHODS: High-grade BilIN (38 cases), PGA (5 cases), and ICPN (25 cases) were examined using capillary immunostaining. Non-neoplastic gallbladders were used as controls. RESULTS: In non-neoplastic gallbladders, a single layer of regularly dotted capillaries (PCP) was located beneath lining epithelia and around non-neoplastic glands (NNGs), including Rokitansky-Aschoff sinus (RAS), presenting a two-layer of lining epithelia and PCP. Intra-luminal components of all cases of high-grade BilIN and PGA and one-third of ICPNs presented a two-layer pattern. In the remaining ICPNs, capillaries were irregular and sparse in intraluminal neoplastic components presenting irregular and complicated lesions. Neoplastic glands in gallbladder walls of high-grade BilIN and ICPN were classifiable into 2 types: glands that were underlain by densely dotted capillaries and those that were not, with the latter suggestive of invasive carcinoma, while the former suggestive of non-invasive neoplasms involving NNGs intraepithelially and/or showing an expanding growth into gallbladder wall (pseudo-invasion). CONCLUSION: A two-layer pattern of lining epithelia and underlining capillaries were preserved in all cases of high-grade BilIN and PGA and one-third of ICPN cases. Presence or absence of dotted capillaries around neoplastic glands may be able to be added as a new pathologic feature to differentiate invasive carcinomas from pseudo-invasion in gallbladder wall.


Asunto(s)
Capilares , Neoplasias de la Vesícula Biliar , Humanos , Neoplasias de la Vesícula Biliar/patología , Masculino , Femenino , Persona de Mediana Edad , Capilares/patología , Anciano , Adenoma/patología , Adulto , Vesícula Biliar/patología , Vesícula Biliar/irrigación sanguínea , Anciano de 80 o más Años , Inmunohistoquímica , Carcinoma in Situ/patología , Invasividad Neoplásica , Diagnóstico Diferencial
18.
BMC Gastroenterol ; 24(1): 146, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38689244

RESUMEN

BACKGROUND: The prevalence of neoplastic polyps in gallbladder polyps (GPs) increases sharply with age and is associated with gallbladder carcinoma (GBC). This study aims to predict neoplastic polyps and provide appropriate treatment strategies based on preoperative ultrasound features in patients with different age level. METHODS: According to the age classification of WHO, 1523 patients with GPs who underwent cholecystectomy from January 2015 to December 2019 at 11 tertiary hospitals in China were divided into young adults group (n=622), middle-aged group (n=665) and elderly group (n=236). Linear scoring models were established based on independent risk variables screened by the Logistic regression model in different age groups. The area under ROC (AUC) to evaluate the predictive ability of linear scoring models, long- and short- diameter of GPs. RESULTS: Independent risk factors for neoplastic polyps included the number of polyps, polyp size (long diameter), and fundus in the young adults and elderly groups, while the number of polyps, polyp size (long diameter), and polyp size (short diameter) in the middle-aged groups. In different age groups, the AUCs of its linear scoring model were higher than the AUCs of the long- and short- diameter of GPs for differentiating neoplastic and non-neoplastic polyps (all P<0.05), and Hosmer-Lemeshow goodness of fit test showed that the prediction accuracy of the linear scoring models was higher than the long- and short- diameter of GPs (all P>0.05). CONCLUSION: The linear scoring models of the young adults, middle-aged and elderly groups can effectively distinguish neoplastic polyps from non-neoplastic polyps based on preoperative ultrasound features.


Asunto(s)
Neoplasias de la Vesícula Biliar , Pólipos , Ultrasonografía , Humanos , Persona de Mediana Edad , Neoplasias de la Vesícula Biliar/diagnóstico por imagen , Neoplasias de la Vesícula Biliar/patología , Femenino , Masculino , Estudios Retrospectivos , Adulto , Pólipos/diagnóstico por imagen , Pólipos/patología , Factores de Edad , Anciano , Factores de Riesgo , Colecistectomía , China/epidemiología , Periodo Preoperatorio , Adulto Joven , Cuidados Preoperatorios
19.
Sci Total Environ ; 928: 172460, 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38615781

RESUMEN

Recently, a substantial increase in gallbladder cancer (GBC) cases has been reported in Bihar, India. The region's groundwater can naturally contain harmful concentrations of arsenic, which appears to be epidemiologically linked to the unusually high incidence. However, the root causes remain largely unexplored. Recent findings of uranium in the state's groundwater may also have associations. This study investigates the geo-spatial epidemiology of GBC in Bihar, India-with a focus on the correlation between environmental carcinogens, particularly arsenic and uranium in groundwater, and the incidence of GBC. Utilizing data from 8460 GBC patients' registration records over an 11-year period at a single health center, the research employs Semi-parametric Geographically Weighted Poisson Regression (S-GWPR) to account for non-stationarity associations and explores significant factors contributing to GBC prevalence at a subdistrict level. The S-GWPR model outperformed the standard Poisson regression model. The estimates suggest that arsenic and uranium concentrations in groundwater did not present significant associations; however, this could be due to the lower resolution of this data at the district level, necessitating higher resolution data for accurate estimates. Other socio-environmental factors included demonstrated significant regional heterogeneity in their association with GBC prevalence. Notably, each 1 % increase in the coverage of well- and canal-irrigated areas is associated with a maximum of 3.0 % and 5.2 % rise in the GBC incidence rate, respectively, likely attributable to carcinogen exposure from irrigation water. Moreover, distance to the health center and domestic electricity connections appear to influence the number of reported GBC cases. The latter suggests that access to electricity might have facilitated the use of groundwater pumps-increasing exposure to carcinogens. The results underscore the necessity for targeted health policies and interventions based on fine-resolution spatial analysis, as well as ongoing environmental monitoring and research to better understand the multifaceted risk factors contributing to GBC.


Asunto(s)
Neoplasias de la Vesícula Biliar , Agua Subterránea , Contaminantes Químicos del Agua , India/epidemiología , Humanos , Neoplasias de la Vesícula Biliar/epidemiología , Agua Subterránea/química , Contaminantes Químicos del Agua/análisis , Exposición a Riesgos Ambientales/estadística & datos numéricos , Arsénico/análisis , Femenino , Uranio/análisis , Masculino , Incidencia , Persona de Mediana Edad , Adulto , Análisis Espacial
20.
Postgrad Med ; 136(3): 278-291, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38635593

RESUMEN

Gallbladder cancer is a common type of biliary tract tumor. Optimal management for early stage cases typically involves radical excision as the primary treatment modality. Various surgical techniques, including laparoscopic, robotic, and navigational surgery, have demonstrated favorable clinical outcomes in radical gallbladder excision. Unfortunately, most patients are ineligible for surgical intervention because of the advanced stage of the disease upon diagnosis. Consequently, non-surgical interventions, such as chemotherapy, radiotherapy, immunotherapy, and targeted therapy, have become the mainstay of treatment for patients in advanced stages. This review focuses on elucidating various surgical techniques as well as advancements in immunotherapy and targeted therapy in the context of recent advancements in gallbladder cancer research.


Asunto(s)
Neoplasias de la Vesícula Biliar , Inmunoterapia , Humanos , Neoplasias de la Vesícula Biliar/terapia , Neoplasias de la Vesícula Biliar/cirugía , Inmunoterapia/métodos , Terapia Molecular Dirigida/métodos , Colecistectomía/métodos
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