RESUMEN
Thailand is among countries with the highest global incidence and mortality rates of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). While viral hepatitis and liver fluke infections have been associated with HCC and iCCA, respectively, other environmental risk factors, overall risk factor commonality and combinatorial roles, and effects on survival have not been systematically examined. We conducted a TIGER-LC consortium-based population study covering all high-incidence areas of both malignancies across Thailand: 837 HCC, 1474 iCCA, and 1112 controls (2011-2019) were comprehensively queried on lifelong environmental exposures, lifestyle, and medical history. Multivariate logistic regression and Cox proportional hazards analyses were used to evaluate risk factors and associated survival patterns. Our models identified shared risk factors between HCC and iCCA, such as viral hepatitis infection, liver fluke infection, and diabetes, including novel and shared associations of agricultural pesticide exposure (OR range of 1.50; 95% CI: 1.06-2.11 to 2.91; 95% CI: 1.82-4.63) along with vulnerable sources of drinking water. Most patients had multiple risk factors, magnifying their risk considerably. Patients with lower risk levels had better survival in both HCC (HR 0.78; 95% CI: 0.64-0.96) and iCCA (HR 0.84; 95% CI: 0.70-0.99). Risk factor co-exposures and their common associations with HCC and iCCA in Thailand emphasize the importance for future prevention and control measures, especially in its large agricultural sector. The observed mortality patterns suggest ways to stratify patients for anticipated survivorship and develop plans to support medical care of longer-term survivors, including behavioral changes to reduce exposures.
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Neoplasias de los Conductos Biliares , Carcinoma Hepatocelular , Colangiocarcinoma , Neoplasias Hepáticas , Humanos , Tailandia/epidemiología , Colangiocarcinoma/epidemiología , Colangiocarcinoma/etiología , Colangiocarcinoma/mortalidad , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/mortalidad , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/etiología , Masculino , Femenino , Persona de Mediana Edad , Neoplasias de los Conductos Biliares/epidemiología , Neoplasias de los Conductos Biliares/etiología , Factores de Riesgo , Anciano , Incidencia , Adulto , Exposición a Riesgos Ambientales/efectos adversos , Estudios de Casos y ControlesRESUMEN
BACKGROUND: Cholangiocarcinoma (CCA) caused by Opisthorchis viverrini is a well-known and significant public health issue in northeastern Thailand; however, a link between pesticide exposure (PE) and CCA risk has not yet been established. Therefore, our research objective was to investigate the relationship between PE and CCA risk. METHODS: A hospital-based matched case-control study was carried out. All cases (in-patients) and controls (out-patients) were volunteers at a tertiary hospital in northeast Thailand. Between 2015 and 2019, 178 incident cases of pathologically-confirmed CCA and 356 controls were selected from the check-up clinic from the Srinagarind Hospital outpatient database (two controls per case). The recruited controls were individually-matched to the CCA cases based on sex, age (±5 years) and admission date (±3 months). During face-to-face interviews, a standardised pre-tested questionnaire was used to collect data. Multivariable conditional logistic regression was used to analyse the data. RESULTS: The respective frequency of PE between the 178 CCA cases and 356 controls was 77.0% versus 87.6% for never used, 14.6% versus 5.3% for have used but stopped and 8.4% versus 7.0% for currently using. After adjusting for the highest educational attainment, smoking behaviour, alcohol use and family history of cancer, PE was not significantly associated with CCA (p-value = 0.086). Using volunteers who have never used PE as the reference group, the respective odds of developing CCA for those who have ever used but have since stopped and are currently using was 2.04 (adjusted OR = 2.04; 95% CI: 1.03-4.04) versus 0.83 (adjusted OR = 0.83; 95% CI: 0.39-1.76) times more likely to develop CCA than those who had never used PE. CONCLUSION: There is no association between PE and the risk of CCA. Notwithstanding the finding, future research should focus on enhancing PE assessment methods that consider complex chemical mixtures, chemicals of interest, historical exposure and exposure pathways. Moreover, there is need for more extensive and longer population-based cohort studies that include younger, non-occupationally exposed individuals during periods of developmental susceptibility.
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Neoplasias de los Conductos Biliares , Colangiocarcinoma , Plaguicidas , Humanos , Colangiocarcinoma/epidemiología , Colangiocarcinoma/inducido químicamente , Estudios de Casos y Controles , Masculino , Femenino , Persona de Mediana Edad , Plaguicidas/efectos adversos , Neoplasias de los Conductos Biliares/epidemiología , Neoplasias de los Conductos Biliares/inducido químicamente , Tailandia/epidemiología , Factores de Riesgo , Adulto , Anciano , Exposición a Riesgos Ambientales/efectos adversosRESUMEN
BACKGROUND: Cholangiocarcinoma (CCA) is a common malignancy in northeastern Thailand. Over the last 4 decades, several policies have been implemented for its prevention, but there has been no update on the trends and relative survival (RS). Our aim was (a) to perform a statistical assessment of the incidence trends of CCA and project future trends, and (b) to estimate relative survival. METHODS: All cases of CCA diagnosed from 1989 through 2013 were abstracted from the Khon Kaen Cancer Registry (KKCR). A jointpoint regression model was used to estimate the annual percentage change (APC) and to project future trends. We also calculated RS. RESULTS: There were 11,711 cases of CCA. The incidence rate increased with an APC of 1.79% (95% confidence interval [CI], -0.2 to 3.8) from 1989 through 2002, and decreased with an APC of -6.09% (95% CI, -8.2 to -3.9) from 2002 through 2013. The projected incidence of CCA should stable over the next 10 years, albeit higher than the world rate. The respective 5-year RS for both sexes for age groups of 30-40, 41-45, 51-60, and 61-98 years was 22.3% (95% CI, 16.8-29.5), 14.3% (95% CI, 12.0-17.0), 8.6% (95% CI, 7.8-10.0), and 7.2% (95% CI, 6.4-8.0). CONCLUSION: The incidence rate of CCA has decreased since 2002, representing a real decline in the risk of CCA. The incidence of CCA is projected to stabilize by 2025. The survival of patients with CCA remains poor.
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Neoplasias de los Conductos Biliares/epidemiología , Colangiocarcinoma/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de los Conductos Biliares/mortalidad , Colangiocarcinoma/mortalidad , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Sistema de Registros , Tasa de Supervivencia , Tailandia/epidemiologíaRESUMEN
INTRODUCTION AND AIM: The carcinogenesis of tubular and papillary cholangiocarcinoma (CCA) differ. The available epidemiologic studies about risk factors for CCA do not differentiate between the tubular and papillary type. The current study investigated the relationship between the number of repeated use of Praziquantel (PZQ) treatments and each type of CCA. MATERIAL AND METHODS: This was a hospital-based, matched, case-control study of patients admitted to Srinagarind Hospital, Khon Kaen University. The patients were 210 pathologically-confirmed cases of CCA, while the controls were 840 subjects diagnosed with other diseases. The 4 controls were individually matched with each case by sex, age, and date of admission. The cases were classified according to location (intrahepatic vs. extrahepatic) and cell type (papillary vs. tubular). Multivariable conditional logistic regression was used for the analysis. RESULTS: After adjusting for confounders, there were statistically significant associations between intrahepatic and papillary CCA and repeated use of PZQ treatment. The respective odds of developing intrahepatic CCA for those who used PZQ once, twice, or more was 1.54 (95%CI:0.92-2.55 ), 2.28 (95%CI:0.91-5.73), and 4.21 (95%CI:1.61-11.05). The respective odds of developing papillary CCA for those who used PZQ once, twice, or more was 1.45 (95%CI:0.80-2.63), 2.96 (95%CI:1.06-8.24), and 3.24 (95%CI:1.09-9.66). There was no association between number of uses of PZQ treatment and developing extrahepatic or tubular CCA. CONCLUSION: The current study found an association between papillary and intrahepatic CCA and repeated use of PZQ treatment. We suggest further study on the risk factors for papillary and tubular CCA should be performed separately.
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Antihelmínticos/efectos adversos , Neoplasias de los Conductos Biliares/inducido químicamente , Carcinoma Papilar/inducido químicamente , Colangiocarcinoma/inducido químicamente , Praziquantel/efectos adversos , Antihelmínticos/administración & dosificación , Neoplasias de los Conductos Biliares/epidemiología , Neoplasias de los Conductos Biliares/patología , Biopsia , Carcinoma Papilar/epidemiología , Carcinoma Papilar/patología , Estudios de Casos y Controles , Colangiocarcinoma/epidemiología , Colangiocarcinoma/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Praziquantel/administración & dosificación , Medición de Riesgo , Factores de Riesgo , Tailandia/epidemiologíaRESUMEN
BACKGROUND AND AIMS: Intraductal papillary neoplasm of the bile duct (IPNB) is a specific type of bile duct tumor. Studies about the surgical outcomes for IPNB are few; therefore, we investigated the survival of patients who underwent curative surgical resection of IPNB. METHODS: We retrospectively reviewed the medical and pathological records of 148 IPNB patients who underwent curative-intent hepatic resection between January 2005 and December 2011, to examine the prognosis of IPNB. All demographic and operative parameters were analyzed the effect on survival of patients. RESULTS: The median survival of IPNB patients was 1326 days with a respective 1, 3, and 5 year overall survival of 83.6% (95%CI: 76.5-88.7), 64.4% (95%CI: 56.0-71.6), and 47% (95%CI: 38.4-55.7). The level of invasiveness of IPNB predicted survival very well. For malignant IPNB, univariate analysis showed that serum CA19-9 level, lymph node metastasis, and completeness of resection were significant prognostic factors. Lymph node metastasis and completeness of resection were found in multivariate analysis to be significantly related to survival of the patients. CONCLUSIONS: The level of invasiveness and lymph node status were found to be associated with patient survival, as was adequacy of surgery. We recommend R0 resection be attempted for patients with IPNB.
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Adenoma/cirugía , Neoplasias de los Conductos Biliares/cirugía , Carcinoma in Situ/cirugía , Resultado del Tratamiento , Adenoma/mortalidad , Adenoma/patología , Anciano , Neoplasias de los Conductos Biliares/mortalidad , Neoplasias de los Conductos Biliares/patología , Procedimientos Quirúrgicos del Sistema Biliar , Biomarcadores de Tumor/sangre , Antígeno CA-19-9/sangre , Carcinoma in Situ/mortalidad , Carcinoma in Situ/patología , Femenino , Hepatectomía , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Análisis Multivariante , Invasividad Neoplásica , Estudios Retrospectivos , Tasa de Supervivencia , Factores de TiempoRESUMEN
Argininosuccinate synthetase (ASS), a key enzyme to synthesize arginine is down regulated in many tumors including hepatocellular carcinoma (HCC). Similar to previous reports, we have found the decrease in ASS expression in poorly differentiated HCC. These ASS(-) tumors are auxotrophic for arginine. Pegylated arginine deiminase (ADI-PEG20), which degrades arginine, has shown activity in these tumors, but the antitumor effect is not robust and hence combination treatment is needed. Herein, we have elucidated the effectiveness of ADI-PEG20 combined with 5-Fluorouracil (5-FU) in ASS(-)HCC by targeting urea cycle and pyrimidine metabolism using four HCC cell lines as model. SNU398 and SNU387 express very low levels of ASS or ASS(-) while Huh-1, and HepG2 express high ASS similar to normal cells. Our results showed that the augmented cytotoxic effect of combination treatment only occurs in SNU398 and SNU387, and not in HepG2 and Huh-1 (ASS(+)) cells, and is partly due to reduced anti-apoptotic proteins X-linked inhibitor of apoptosis protein (XIAP), myeloid leukemia cell differentiation protein (Mcl-1) and B-cell lymphoma-2 (Bcl-2). Importantly, lack of ASS also influences essential enzymes in pyrimidine synthesis (carbamoyl-phosphate synthetase2, aspartate transcarbamylase and dihydrooratase (CAD) and thymidylate synthase (TS)) and malate dehydrogenase-1 (MDH-1) in TCA cycle. ADI-PEG20 treatment decreased these enzymes and made them more vulnerable to 5-FU. Transfection of ASS restored these enzymes and abolished the sensitivity to ADI-PEG20 and combination treatment. Overall, our data suggest that ASS influences multiple enzymes involved in 5-FU sensitivity. Combining ADI-PEG20 and 5-FU may be effective to treat ASS(-)hepatoma and warrants further clinical investigation.
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Arginina/metabolismo , Argininosuccinato Sintasa/deficiencia , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/metabolismo , Fluorouracilo/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Adulto , Anciano , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Apoptosis/efectos de los fármacos , Apoptosis/genética , Argininosuccinato Sintasa/genética , Argininosuccinato Sintasa/metabolismo , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Femenino , Fluorouracilo/farmacología , Expresión Génica , Regulación Enzimológica de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Hidrolasas/farmacología , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Modelos Biológicos , Polietilenglicoles/farmacología , Resultado del TratamientoRESUMEN
BACKGROUND: Infection by the liver fluke, Opisthorchis viverrini, remains an important public health problem in Thailand and has resulted in the highest prevalence of infection and incidence of subsequent cholangiocarcinoma (CCA) in the world. Praziquantel (PZQ) is the antihelminthic drug of choice for treatment. Previous studies in hamsters showed that repeated infection and PZQ treatment could increase the risk of CCA. However, the few available epidemiology studies in humans have shown unclear evidence of an increased risk of CCA with frequency of PZQ intake. The present study investigated the relationship between the number of repeated PZQ treatments and CCA. METHODS: A hospital-based matched case-control study was conducted. All cases and controls were inpatients of a tertiary hospital in Northeast Thailand. During 2012-2014 a total of 210 incident cases of pathologically diagnosed CCA and 840 control subjects were selected from a hospital inpatient database (four controls per case). The four recruited controls were individually matched with CCA cases by gender, age and date of admission. Data were collected in face-to-face interviews using a standardised pre-tested questionnaire. Multivariable conditional logistic regression was used in the analysis of the data. RESULTS: The frequencies of PZQ usage among the 210 cases and 840 controls were 48.6 vs. 66.0 for never, 32.9 vs. 24.4 for once, 8.6 vs. 4.9 for twice, and 10.0% vs. 4.8% for more than twice, respectively. There was a statistically significant dose-response relationship (p < 0.001). Compared with subjects who never used PZQ, those who used the medication once, twice, and more than twice were 1.49, 1.82, and 2.30 times more likely to develop CCA (95% confidence intervals: 1.02 - 2.20, 0.92 - 3.60, and 1.20 - 4.40). These odds ratios (adjusted ORs) had already been adjusted for the effects of eating raw fish, a family history of cancer, and highest educational attainment. Additional PZQ usage increased the odds of developing CCA by 23.0% (adjusted OR = 1.23; 95% CI: 1.07 - 1.43). CONCLUSIONS: The findings show that repeated PZQ treatments are associated with an increased risk of CCA. Paradoxically, this contradicts the common belief that repeated PZQ treatments decrease the risk of CCA. The study also showed a strong association between the number of repeated PZQ treatments and the consumption of raw freshwater fish. This suggests that repeated PZQ treatments may be a surrogate marker of habit of eating raw fish.
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Antihelmínticos/efectos adversos , Neoplasias de los Conductos Biliares/inducido químicamente , Colangiocarcinoma/inducido químicamente , Praziquantel/efectos adversos , Adulto , Anciano , Antihelmínticos/administración & dosificación , Neoplasias de los Conductos Biliares/epidemiología , Estudios de Casos y Controles , Colangiocarcinoma/epidemiología , Fascioliasis/tratamiento farmacológico , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Praziquantel/administración & dosificación , Factores de Riesgo , Tailandia/epidemiologíaRESUMEN
BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive tumor of the bile duct, and a significant public health problem in East Asia, where it is associated with infection by the parasite Opisthorchis viverrini. ICC is often detected at an advanced stage and with a poor prognosis, making a biomarker for early detection a priority. METHODS: We have comprehensively profiled miRNA expression levels in ICC tumor tissue using small RNA-Seq and validated these profiles using quantitative PCR on matched plasma samples. RESULTS: Distinct miRNA profiles were associated with increasing histological differentiation of ICC tumor tissue. We also observed that histologically normal tissue adjacent to ICC tumor displayed miRNA expression profiles more similar to tumor than liver tissue from healthy donors. In plasma samples, an eight-miRNA signature associated with ICC, regardless of the degree of histological differentiation of its matched tissue, forming the basis of a circulating miRNA-based biomarker for ICC. CONCLUSIONS: The association of unique miRNA profiles with different ICC subtypes suggests the involvement of specific miRNAs during ICC tumor progression. In plasma, an eight-miRNA signature associated with ICC could form the foundation of an accessible (plasma-based) miRNA-based biomarker for the early detection of ICC.
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Neoplasias de los Conductos Biliares/sangre , Biomarcadores/sangre , Colangiocarcinoma/sangre , MicroARNs/sangre , Animales , Neoplasias de los Conductos Biliares/genética , Neoplasias de los Conductos Biliares/microbiología , Neoplasias de los Conductos Biliares/patología , Colangiocarcinoma/genética , Colangiocarcinoma/microbiología , Colangiocarcinoma/patología , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , MicroARNs/genética , MicroARNs/aislamiento & purificación , Persona de Mediana Edad , Anotación de Secuencia Molecular , Opisthorchis/patogenicidad , PronósticoRESUMEN
BACKGROUND & AIMS: Intrahepatic cholangiocarcinoma (ICC) is a significant public health problem in East Asia, where it is strongly associated with chronic infection by the food-borne parasite Opisthorchis viverrini (OV). We report the first comprehensive miRNA expression profiling by microarray of the most common histologic grades and subtypes of ICC: well differentiated, moderately differentiated, and papillary ICC. METHODS: MicroRNA expression profiles from FFPE were compared among the following: ICC tumour tissue (n = 16), non-tumour tissue distally macrodissected from the same ICC tumour block (n = 15), and normal tissue (n = 13) from individuals undergoing gastric bypass surgery. A panel of deregulated miRNAs was validated by qPCR. RESULTS: Each histologic grade and subtype of ICC displayed a distinct miRNA profile, with no cohort of miRNAs emerging as commonly deregulated. Moderately differentiated ICC showed the greatest miRNA deregulation in quantity and magnitude, followed by the papillary subtype, and then well differentiated ICC. Moreover, when ICC tumour tissues were compared to adjacent non-tumour tissue, similar miRNA dysregulation profiles were observed. CONCLUSIONS: We show that common histologic grades and subtypes of ICC have distinct miRNA profiles. As histological grade and subtypes are associated with ICC aggressiveness, these profiles could be used to enhance the early detection and improve the personalised treatment for ICC. These findings also suggest the involvement of specific miRNAs during ICC tumour progression and differentiation. We plan to use these insights to (a) detect these profiles in circulation and (b) conduct functional analyses to decipher the roles of miRNAs in ICC tumour differentiation.
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Neoplasias de los Conductos Biliares , Conductos Biliares Intrahepáticos , Colangiocarcinoma , MicroARNs/genética , Animales , Neoplasias de los Conductos Biliares/etiología , Neoplasias de los Conductos Biliares/genética , Neoplasias de los Conductos Biliares/patología , Conductos Biliares Intrahepáticos/patología , Colangiocarcinoma/etiología , Colangiocarcinoma/genética , Colangiocarcinoma/patología , Femenino , Perfilación de la Expresión Génica/métodos , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Opistorquiasis/complicaciones , Opistorquiasis/parasitología , Opisthorchis/aislamiento & purificación , PronósticoRESUMEN
Hepatocellular carcinoma (HCC) is a molecularly heterogeneous solid malignancy, and its fitness may be shaped by how its tumor cells evolve. However, ability to monitor tumor cell evolution is hampered by the presence of numerous passenger mutations that do not provide any biological consequences. Here we develop a strategy to determine the tumor clonality of three independent HCC cohorts of 524 patients with diverse etiologies and race/ethnicity by utilizing somatic mutations in cancer driver genes. We identify two main types of tumor evolution, i.e., linear, and non-linear models where non-linear type could be further divided into classes, which we call shallow branching and deep branching. We find that linear evolving HCC is less aggressive than other types. GTF2IRD2B mutations are enriched in HCC with linear evolution, while TP53 mutations are the most frequent genetic alterations in HCC with non-linear models. Furthermore, we observe significant B cell enrichment in linear trees compared to non-linear trees suggesting the need for further research to uncover potential variations in immune cell types within genomically determined phylogeny types. These results hint at the possibility that tumor cells and their microenvironment may collectively influence the tumor evolution process.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Filogenia , Oncogenes , Mutación , Microambiente Tumoral/genéticaRESUMEN
Phosphatidylinositol 3-kinase (PI3K) signaling plays a critical role in cholangiocarcinoma (CCA), as well as anti-cancer drug resistance and autophagy, the type II program cell death regulation. In this work, we aimed to: (1) determine the expression levels of several key components of PI3K signaling and (2) evaluate whether NVP-BEZ235, a novel dual PI3K/mTOR inhibitor, could inhibit CCA cell growth. Immunohistochemistry for p85α, p110α, AKT, p-AKT (T308), mTOR, p-mTOR (S2448), GSK-3ß, p-GSK-3ß (S9), PTEN, and p-PTEN (S380, T382/383) was performed in 30 CCA patients. Western blotting was used to analyze PTEN and p-PTEN expression in the cell lines (KKU-OCA17, KKU-100, KKU-M055, KKU-M139, KKU-M156, KKU-M213, and KKU-M214). The effects of NVP-BEZ235 on CCA cells were evaluated using a growth inhibition assay, flow cytometer and migration assay. Increased activation of PI3K/AKT signaling was reproducibly observed in the CCA tissues. The expression of p85α, mTOR, and GSK-3ß was significantly correlated with metastasis. Interestingly, PTEN suppression by loss of expression or inactivation by phosphorylation was observed in the majority of patients. Furthermore, NVP-BEZ235 effectively inhibited CCA cell growth and migration through reduced AKT and mTOR phosphorylation and significantly induced G1 arrest without apoptosis induction, although increase autophagy response was observed. In conclusion, the constitutive activation of PI3K/AKT pathway in CCA is mainly due to PTEN inactivation by either loss of expression or phosphorylation along with an increased expression in its pathway components heralding a poor prognosis for CCA patients. This work also indicates that inhibition of PI3K and mTOR activity by the inhibitor NVP-BEZ235 has anti-cancer activity against CCA cells which might be further tested for CCA treatment.
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Neoplasias de los Conductos Biliares/metabolismo , Conductos Biliares Intrahepáticos , Colangiocarcinoma/metabolismo , Fosfatidilinositol 3-Quinasa/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Adulto , Anciano , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Neoplasias de los Conductos Biliares/patología , Western Blotting , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Colangiocarcinoma/tratamiento farmacológico , Colangiocarcinoma/patología , Relación Dosis-Respuesta a Droga , Activación Enzimática/efectos de los fármacos , Femenino , Glucógeno Sintasa Quinasa 3/metabolismo , Glucógeno Sintasa Quinasa 3 beta , Humanos , Imidazoles/farmacología , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Fosfohidrolasa PTEN/metabolismo , Inhibidores de las Quinasa Fosfoinosítidos-3 , Fosforilación/efectos de los fármacos , Quinolinas/farmacología , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/antagonistas & inhibidoresRESUMEN
Purpose: Globally, emergency departments (ED) are faced with an overcrowding problem. This issue is further compounded due to the multitude of contributing factors. Point of Care ultrasound (POCUS), especially when performed in prehospital care, that is before the patient is admitted to the ED has a high potential to reduce time of diagnosis and time of investigation which leads to shorter ED length of stay (LOS). The primary focus was on variances in ED LOS between the prehospital POCUS group and the standard care group. Patients and Methods: A cross-sectional study was conducted on prehospital patients who were admitted to the ED at Srinagarind Hospital, Thailand, from January to December 2021. We divided patients into two groups including patients who obtained prehospital POCUS (the prehospital POCUS group) and patients who received standard care treatment in which there was no prehospital POCUS performed (the standard care group). POCUS and ED medical records were documented and submitted for analysis. Results: Of 1348 prehospital patients, 840 were enrolled in this study: 169 with prehospital POCUS and 671 with standard care. Median LOS in the prehospital POCUS group was 159 min (IQR 89,289) versus 165 (IQR 102,330) in the standard care group (p = 0.125). Further imaging diagnostic test which affected ED LOS more than four hours was lower in the prehospital POCUS group (adjusted odds ratio [OR], 0.92; 95% confidence intervals [CI], 0.729-1.666) than in the standard care group. The factor associated with increased odds of ED LOS more than four hour in the prehospital POCUS group was admission to hospital (adjusted OR 1.88; 95% CI, 1.230-2.239). Conclusion: Patients evaluated with prehospital POCUS had a shorter LOS than the only standard care treatment without statistical significance.
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BACKGROUND: Enhanced recovery after surgery (ERAS) program has been proved to improve postoperative outcome for many surgical procedures, including liver resection. There was limited evidence regarding the feasibility and benefit of ERAS in patients who underwent liver resection for cholangiocarcinoma. AIM: To evaluate the feasibility of ERAS in patients who underwent liver resection for cholangiocarcinoma and its association with patient outcomes. METHODS: We retrospectively analyzed 116 cholangiocarcinoma patients who underwent hepatectomy at Srinagarind Hospital, Khon Kaen University between January 2015 and December 2016. The primary outcome was the compliance with ERAS. To determine the association between ERAS compliance and patient outcomes. the patients were categorized into those adhering more than and equal to 50% (ERAS ≥ 50), and below 50% (ERAS < 50) of all components. Details on type of surgical procedure, preoperative and postoperative care, tumor location, postoperative laboratory results, and survival time were evaluated. The compliance with ERAS was measured by the percentage of ERAS items achieved. The Kaplan-Meier curve was used for survival analysis. RESULTS: The median percentage of ERAS goals achieved was 40% (± 12%). Fourteen patients (12.1%) were categorized into the ERAS ≥ 50 group, and 102 patients were in the ERAS < 50 group. Postoperative hospital stay was significantly shorter in the ERAS ≥ 50 group [8.9 d, 95% confidence interval (CI): 7.3-10.4 d] than in the ERAS < 50 group (13.7 d, 95%CI: 12.2-15.2 d) (P = 0.0217). No hepatobiliary-related complications or in-hospital mortality occurred in the ERAS ≥ 50 group. Overall survival was significantly higher in the ERAS ≥ 50 group. The median survival of the patients in the ERAS < 50 group was 1257 d (95%CI: 853.2-1660.8 d), whereas that of the patients in the ERAS ≥ 50 group was not reached. CONCLUSION: Overall ERAS compliance for patients who underwent liver resection for cholangiocarcinoma is poor. Greater ERAS compliance could predict in-hospital, short-term, and long-term outcomes of the patients.
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This study evaluates the pan-serological profiles of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) compared to several diseased and non-diseased control populations to identify risk factors and biomarkers of liver cancer. We used phage immunoprecipitation sequencing, an anti-viral antibody screening method using a synthetic-phage-displayed human virome epitope library, to screen patient serum samples for exposure to over 1,280 strains of pathogenic and non-pathogenic viruses. Using machine learning methods to develop an HCC or iCCA viral score, we discovered that both viral scores were positively associated with several liver function markers in two separate at-risk populations independent of viral hepatitis status. The HCC score predicted all-cause mortality over 8 years in patients with chronic liver disease at risk of HCC, while the viral hepatitis status was not predictive of survival. These results suggest that non-hepatitis viral infections may contribute to HCC and iCCA development and could be biomarkers in at-risk populations.
Asunto(s)
Neoplasias de los Conductos Biliares , Carcinoma Hepatocelular , Colangiocarcinoma , Hepatitis Viral Humana , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Viroma , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/patología , Biomarcadores , Conductos Biliares Intrahepáticos/patología , Neoplasias de los Conductos Biliares/diagnóstico , Neoplasias de los Conductos Biliares/patología , Hepatitis Viral Humana/complicacionesRESUMEN
OBJECTIVES: To investigate whether Helicobacter spp. infection and the cagA of H. pylori are associated with hepatobiliary pathology, specifically biliary inflammation, cell proliferation and cholangiocarcinoma (CCA). METHODS: Helicobacter species including H. pylori, H. bilis and H. hepaticus were detected in the specimens using the polymerase chain reaction (PCR). Biliary inflammation of the liver and gallbladders was semi-quantitatively graded on hematoxylin and eosin (H&E)-stained slides. Biliary proliferation was evaluated by immunohistochemistry using the Ki-67-labelling index. RESULTS: Helicobacter pylori was found in 66.7%, 41.5% and 25.0% of the patients in the CCA, cholelithiasis and control groups (P < 0.05), respectively. By comparison, H. bilis was found in 14.9% and 9.4% of the patients with CCA and cholelithiasis, respectively (P > 0.05), and was absent in the control group. The cagA gene of H. pylori was detected in 36.2% and 9.1% of the patients with CCA and cholelithiasis, respectively (P < 0.05). Among patients with CCA, cell inflammation and proliferation in the liver and gallbladder were significantly higher among those DNA H. pylori positive than negative. CONCLUSIONS: The present findings suggest that H. pylori, especially the cagA-positive strains, may be involved in the pathogenesis of hepatobiliary diseases, especially CCA through enhanced biliary cell inflammation and proliferation.
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Neoplasias de los Conductos Biliares/microbiología , Conductos Biliares Intrahepáticos/microbiología , Proliferación Celular , Colangiocarcinoma/microbiología , Colangitis/microbiología , Infecciones por Helicobacter/microbiología , Helicobacter pylori/aislamiento & purificación , Antígenos Bacterianos/genética , Pueblo Asiatico , Proteínas Bacterianas/genética , Neoplasias de los Conductos Biliares/química , Neoplasias de los Conductos Biliares/etnología , Neoplasias de los Conductos Biliares/patología , Conductos Biliares Intrahepáticos/química , Conductos Biliares Intrahepáticos/patología , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Colangiocarcinoma/química , Colangiocarcinoma/etnología , Colangiocarcinoma/patología , Colangitis/etnología , Colangitis/patología , Infecciones por Helicobacter/etnología , Helicobacter hepaticus/aislamiento & purificación , Helicobacter pylori/genética , Helicobacter pylori/patogenicidad , Humanos , Inmunohistoquímica , Antígeno Ki-67/análisis , Reacción en Cadena de la Polimerasa , Tailandia/epidemiologíaRESUMEN
Purpose: Cardiac, lung, and inferior vena cava (IVC) ultrasound are commonly performed in the care of emergency patients especially patient presented with hypotension or shock. However, the literature indicated the limitation of IVC to assess shocked patients. This study aims to determine the efficacy of combined cardiac and lung ultrasound for evaluation the etiology of shock. Materials and Methods: A cross-sectional study was conducted on patient with shock at emergency department, Srinagarind Hospital, Thailand, from January to December 2021. Adult shocked patients who met the criteria were included in this study. Ultrasound and emergency department medical records were documented and analyzed as sensitivity, specificity, predictive value, negative predictive value, diagnostic accuracy, and Cohen's kappa coefficient (κ). Results: One hundred and two who met the criteria were enrolled. Combined cardiac and lung scans were found to be accurate 99.02% and 93.04% in obstructive and cardiogenic shock. In patients with obstructive shock was the almost perfect agreement, (κ) = 0.85. However, distributive, and hypovolemic shock had the low concordance with the final hospital diagnosis, (κ) = 0.37 and 0.43, respectively. Conclusions: The integration of cardiac and lung ultrasound can be effectively used to narrow differential diagnosis of shock.
RESUMEN
INTRODUCTION: Prehospital ultrasounds can be considered a new form of diagnostic tool when taking into account their small structure and due to the fact that nowadays, they are used in the care of emergency patients. However, at present, there is no study regarding the advantage of ultrasound usage in prehospital settings in Thailand. STUDY OBJECTIVE: This study aims to determine the sonographic characteristics recorded by handheld ultrasounds used in prehospital care and the diagnostic accuracy of ultrasounds for prehospital patients. METHODS: A cross-sectional study was conducted on prehospital patients who underwent point-of-care ultrasound (POCUS) examination on Emergency Medical Service (EMS) operations at Srinagarind Hospital, Thailand from January 2021 through December 2021. The ultrasound images, the electronic emergency department medical records, and the EMS database were recorded and reviewed by a team of emergency physicians. The quality of prehospital ultrasound examinations was assessed by comparing the diagnoses at the scene with those taken at the hospital. RESULTS: One hundred sixty-nine prehospital patients who received POCUS examinations were examined over a one-year period. All (100.0%) of the scans were for medical cases. No ultrasound protocol was used in the prehospital care. Two hundred eight POCUS examinations were performed in this study. The most common POCUS indication was dyspnea (45.6%), followed by hypotension/shock (30.1%), and finally syncope (8.2%). The most common area where POCUS was performed was on the lung (37.0%), followed by the inferior vena cava (30.8%), and finally for cardiac cases (26.4%). This study found that 34.9% of sonographic findings could be considered abnormal. The diagnoses of prehospital patients were confirmed by using POCUS in 66 cases (39.1%) with the accuracy of prehospital diagnosis reaching a peak of 75.8%. CONCLUSION: This study shows POCUS examinations can be effectively used in prehospital care. The prehospital diagnosis given by physicians administering treatment who used POCUS examinations correlated with the in-hospital diagnosis.
Asunto(s)
Servicios Médicos de Urgencia , Sistemas de Atención de Punto , Estudios Transversales , Servicios Médicos de Urgencia/métodos , Servicio de Urgencia en Hospital , Humanos , Pruebas en el Punto de Atención , UltrasonografíaRESUMEN
Point of care ultrasound (POCUS) competency is now required learning for emergency medicine trainees. However, there is a wide range of areas that need to be assessed when determining competence. Therefore, this study aims to evaluate competence levels of POCUS skill acquisition including the areas of image acquisition, image interpretation and clinical integration of the emergency medicine residents while on shift in real clinical practice situations. This was a retrospective descriptive study. This study was conducted at Srinagarind Hospital, Thailand from January 2021 through December 2021. The data were collected and reviewed from electronic medical records, ultrasound images and video clips. All POCUS competency skills were assessed by researcher staff. Our results demonstrated that our learners had overall satisfactory competence of image acquisition, satisfactory image interpretation skills, and good clinical integration skills. However, obstetrics and gynecology (OB-GYN) ultrasound scores were poor and cardiac ultrasound had the most varied score of image quality. This study clearly showed the measurable benefits of a POCUS course being integrated into real clinical practice.
Asunto(s)
Competencia Clínica , Sistemas de Atención de Punto , Servicio de Urgencia en Hospital , Humanos , Estudios Retrospectivos , Ultrasonografía/métodosRESUMEN
INTRODUCTION: Motorcycles can be considered a new form of smart vehicle when taking into account their small and modern structure and due to the fact that nowadays, they are used in the new role of ambulance to rapidly reach emergency patients in large cities with traffic congestion. However, there is no study regarding the measuring of access time for motorcycle ambulances (motorlances) in large cities of Thailand. STUDY OBJECTIVE: This study aims to compare access times to patients between motorlances and conventional ambulances, including analysis of the use of automated external defibrillators (AEDs) installed on motorlances to contribute to the sustainable development of public health policies. METHODS: A cross-sectional study was conducted on all motorlance operations in Emergency Medical Services (EMS) at Srinagarind Hospital, Thailand from January 2019 through December 2020. Data were recorded using a national standard operation record form for Thailand. RESULTS: Two hundred seventy-one motorlance operations were examined over a two-year period. A total of 52.4% (N = 142) of the patients were male. The average times from dispatch to vehicle (motorlance and traditional ambulance) being en route (activation time) for motorlance and ambulance in afternoon shift were 0.59 minutes and 1.45 minutes, respectively (P = .004). The average motorlance response time in the afternoon shift was 6.12 minutes, and ambulance response time was 9.10 minutes at the same shift. Almost all of the motorlance operations (97.8%) were found to have no access to AED equipment installed in public areas. The average time from dispatch to AED arrival on scene (AED access time) was 5.02 minutes. CONCLUSION: The response time of motorlances was shorter than a conventional ambulance, and the use of AEDs on a motorlance can increase the chances of survival for patients with cardiac arrest outside the hospital in public places where AEDs are not available.