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UNLABELLED: Whether aspirin use is protective against cholangiocarcinoma (CCA) remains unclear. We determined the association between aspirin use and other risk factors for each CCA subtype individually. In a hospital-based case-control study, 2395 CCA cases (1169 intrahepatic, 995 perihilar, and 231 distal) seen at the Mayo Clinic, Rochester, MN, from 2000 through 2014 were enrolled. Controls selected from the Mayo Clinic Biobank were matched two to one with cases by age, sex, race, and residence (n = 4769). Associations between aspirin use, other risk factors, and CCA risk were determined. Aspirin was used by 591 (24.7%) CCA cases and 2129 (44.6%) controls. There was a significant inverse association of aspirin use with all CCA subtypes, with adjusted odds ratios (AORs) of 0.35 (95% confidence interval [CI], 0.29-0.42), 0.34 (95% CI 0.27-0.42), and 0.29 (95% CI 0.19-0.44) for intrahepatic, perihilar, and distal CCA, respectively (P < 0.001 for all). Primary sclerosing cholangitis was more strongly associated with perihilar (AOR = 453, 95% CI 104-999) than intrahepatic (AOR = 93.4, 95% CI 27.1-322) or distal (AOR = 34.0, 95% CI 3.6-323) CCA, whereas diabetes was more associated with distal (AOR = 4.2, 95% CI 2.5-7.0) than perihilar (AOR = 2.9, 95% CI 2.2-3.8) or intrahepatic (AOR = 2.5, 95% CI 2.0-3.2) CCA. Cirrhosis not related to primary sclerosing cholangitis was associated with both intrahepatic and perihilar CCA, with similar AORs of 14. Isolated inflammatory bowel disease without primary sclerosing cholangitis was not associated with any CCA subtype. CONCLUSIONS: Aspirin use was significantly associated with a 2.7-fold to 3.6-fold decreased risk for the three CCA subtypes; our study demonstrates that individual risk factors confer risk of different CCA subtypes to different extents. (Hepatology 2016;64:785-796).
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Aspirina/uso terapéutico , Neoplasias de los Conductos Biliares/epidemiología , Colangiocarcinoma/epidemiología , Inhibidores de la Ciclooxigenasa/uso terapéutico , Anciano , Neoplasias de los Conductos Biliares/prevención & control , Estudios de Casos y Controles , Colangiocarcinoma/prevención & control , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Minnesota/epidemiología , Factores de RiesgoRESUMEN
Fibroblast growth factors, or FGFs, are a large family of polypeptide cytokines exhibiting a pleiotropy of functions, from cell growth to angiogenesis, wound healing, and tissue repair. This review broadly covers the genetics and protein expression of the FGF family members and the signaling pathways involved in FGF-mediated growth regulation. We emphasize the role of FGFs in the pathogenesis of hepatocellular carcinoma (HCC), including their effects on regulation of the tumor microenvironment and angiogenesis. Finally, we present current views on FGF's potential role as a prognostic marker in clinical practice, as well as its potential as a therapeutic target in HCC.
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Carcinoma Hepatocelular/metabolismo , Factores de Crecimiento de Fibroblastos/metabolismo , Neoplasias Hepáticas/metabolismo , Transducción de Señal/fisiología , Microambiente Tumoral/fisiología , Biomarcadores de Tumor/metabolismo , HumanosRESUMEN
INTRODUCTION: Pancreatic polypeptide (PP) is a hormone secreted by islet cells of the ventral pancreas. It has been proposed that a blunted PP response to a mixed meal can distinguish diabetes mellitus (DM) secondary to pancreatic disease from other types of DM. We performed a proof of concept study to determine if PP response to a mixed meal discriminates DM secondary to pancreatic cancer (PaCDM) from type 2 DM (T2DM). METHODS: We studied 18 subjects with new onset DM (PaCDM (n = 9) and T2DM (n = 9); matched for age and gender). Serum PP levels were measured at 0, 30, and 60 min following a mixed meal. Increases in PP levels from baseline were compared using the Wilcoxon test. RESULTS: In PaCDM the PP increase following a mixed meal was less than T2DM at 30 min (median 60.0%, IQR, 33.0-119.8 vs. 134.5%, IQR, 117.5-265.9; p = 0.03), but statistically similar at 60 min (median 55.8%, interquartile range (IQR) 23.7-121.5 vs. 100.0%, IQR, 47.7-202.5; p = 0.17). In PaCDM subjects, the PP increase over baseline was smaller in those with a tumor located in the pancreatic head (n = 6) compared to the body/tail (n = 3) at 30 min (41.3% vs. 158.7%, p = 0.02) and at 60 min (37.4% vs. 167.4%,p = 0.04). CONCLUSIONS: Subjects with PaCDM have a blunted PP response to a mixed meal compared to T2DM. However, the blunted PP response is only observed in those PaC subjects with a tumor located in the head of the pancreas. Confirmation in larger studies may suggest this could be used to aid screening for sporadic PaC.
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Carcinoma Ductal Pancreático/metabolismo , Complicaciones de la Diabetes/metabolismo , Diabetes Mellitus/metabolismo , Neoplasias Pancreáticas/metabolismo , Polipéptido Pancreático/metabolismo , Anciano , Carcinoma Ductal Pancreático/complicaciones , Carcinoma Ductal Pancreático/patología , Diabetes Mellitus/diagnóstico , Diabetes Mellitus Tipo 2/diagnóstico , Diagnóstico Diferencial , Ingestión de Alimentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Páncreas/patología , Neoplasias Pancreáticas/complicaciones , Neoplasias Pancreáticas/patología , Estudios ProspectivosRESUMEN
Chronic hepatitis B and C infection are the leading causes of hepatocellular carcinoma and liver related death in the world and in the United States respectively. Screening guidelines have been developed based on estimated prevalence determined by NHANES data. However, individuals with the most risk of chronic infection (incarcerated, homeless, immigrants, nursing home residents, and hospitalized persons) are underrepresented in this cohort leading to an underestimation of the true prevalence of chronic hepatitis B and C infection. This has led to recent updates in the screening guidelines. This review examines the change in the guidelines, the likely true seroprevalence of hepatitis B and C virus, as well as the burden of chronic infection in this population.
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Hepatitis B Crónica/economía , Hepatitis B Crónica/epidemiología , Hepatitis C Crónica/economía , Hepatitis C Crónica/epidemiología , Análisis Costo-Beneficio , Guías como Asunto , Hepatitis B Crónica/diagnóstico , Hepatitis C Crónica/diagnóstico , Humanos , Vigilancia de la Población , Estados Unidos/epidemiologíaRESUMEN
Genetic risk factors for cholangiocarcinoma (CCA) remain poorly understood. We assessed the effect of single-nucleotide polymorphisms (SNPs) of genes modulating inflammation or carcinogenesis on CCA risk and survival. We conducted a case-control, candidate gene association study of 370 CCA patients and 740 age-, sex-, and residential area-matched healthy controls. Eighteen functional or putatively functional SNPs in nine genes were genotyped. The log-additive genotype effects of SNPs on CCA risk and survival were determined using logistic regression and the log-rank test, respectively. Initial analysis identified significant associations between SNP rs2143417 and rs689466 in cyclooxygenase 2 (COX-2) and CCA risk, after adjusting for multiple comparisons (cutoff of P = 0.0028). However, these findings were not replicated in another independent cohort of 212 CCA cases and 424 matched controls. No significant association was found between any SNP and survival of CCA patients. Although COX-2 has been shown to contribute to cholangiocarcinogenesis, the COX-2 SNPs tested were not associated with risk of CCA. This study shows a lack of association between variants of genes related to inflammation and carcinogenesis and CCA risk and survival. Other factors than these genetic variants may play more important roles in CCA risk and survival.
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Neoplasias de los Conductos Biliares/epidemiología , Carcinogénesis/genética , Colangiocarcinoma/epidemiología , Inflamación/genética , Anciano , Neoplasias de los Conductos Biliares/genética , Neoplasias de los Conductos Biliares/mortalidad , Estudios de Casos y Controles , Colangiocarcinoma/genética , Colangiocarcinoma/mortalidad , Colangitis Esclerosante/genética , Ciclooxigenasa 2/genética , Citocinas/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Subfamilia K de Receptores Similares a Lectina de Células NK/genética , Polimorfismo de Nucleótido Simple , Factores de RiesgoRESUMEN
Telomere biology is central to the maintenance of genomic stability and telomeric dysfunction is thought to be an early stage in carcinogenesis. Reports of telomere lengths and their ascribed colorectal cancer (CRC) risks have been discordant, with both very short and very long telomeres implicated. Nevertheless, telomeres appear to play a very central role in cancer initiation. Telomere length changes also appear to impact disease burden, progression, and overall survival. This review covers contemporary views on telomere biology and CRC risk, with a brief overview of analytical methods employed in telomere measurement. We conclude with arguments in favor of including telomere assessment in the molecular profiling of CRCs.
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Aberrations in telomere length and telomere maintenance contribute to cancer development. In this article, we review the basic principles of telomere length in normal and tumor tissue and the presence of the two main telomere maintenance pathways as they pertain to gastrointestinal tract cancer. Peripheral blood telomeres are shorter in patients with many types of gastrointestinal tract cancers. Telomere length in tumor DNA also appears to shorten early in cancer development. Tumor telomere shortening is often accompanied by telomerase activation to protect genetically damaged DNA from normal cell senescence or apoptosis, allowing immortalized but damaged DNA to persist. Alternative lengthening of telomeres is another mechanism used by cancer to maintain telomere length in cancer cells. Telomerase and alternative lengthening of telomeres activators and inhibitors may become important chemopreventive or chemotherapeutic agents as our understanding of telomere biology, specific telomere-related phenotypes and its relationship to carcinogenesis increases.