RESUMEN
The histological diagnosis of type 1 autoimmune pancreatitis (AIP) based on the findings obtained by an endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) is feasible, but the diagnostic consistency of this method has not been confirmed. We determined the interobserver agreement among 20 pathologists regarding the diagnosis of type 1 AIP, including the distinction from pancreatic ductal adenocarcinoma (PDAC) using large tissue samples obtained by EUS-FNB. After guidance for diagnosing AIP with biopsy tissues was provided, a round 2 was performed. The median sensitivity and specificity for diagnosing PDAC vs. non-neoplastic diseases were 95.2% and 100%, respectively. In groups of specialists (n = 7) and the generalists (n = 13), Fleiss' к-values increased from 0.886 to 0.958 and from 0.750 to 0.816 in round 2. The concordance was fair or moderate for obliterative phlebitis and storiform fibrosis but slight for ductal lesion of type 1 AIP. Discordant results were due to ambiguous findings and biopsy tissue limitations. Among the specialists, the ratio of cases with perfect agreement regarding the presence of storiform fibrosis increased in round 2, but agreement regarding obliterative phlebitis or ductal lesions was not improved. Although the histological definite diagnosis of type 1 AIP was achieved by most observers in > 60% of the cases, the confidence levels varied. Because some ambiguities exist, the histological diagnostic levels based on the diagnostic criteria of type 1 AIP should not be taken for granted. Guidance is effective for improving accurate PDAC diagnoses (notably by recognizing acinar-ductal metaplasia) and for evaluating storiform fibrosis.
Asunto(s)
Enfermedades Autoinmunes , Pancreatitis Autoinmune , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Flebitis , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/patología , Pancreatitis Autoinmune/diagnóstico , Biopsia con Aguja Fina/métodos , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/patología , Fibrosis , Humanos , Variaciones Dependientes del Observador , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patología , Flebitis/patología , Ultrasonografía Intervencional , Neoplasias PancreáticasRESUMEN
We previously showed that male Tsumura Suzuki obese diabetes (TSOD) mice, a spontaneous mouse model of metabolic syndrome, manifested gut dysbiosis and subsequent disruption of the type and quantity of plasma short-chain fatty acids (SCFAs), and daily coffee intake prevented nonalcoholic steatohepatitis in this mouse model. Here, we present a preliminary study on whether coffee and its major components, caffeine and chlorogenic acid, would affect the gut dysbiosis and the disrupted plasma SCFA profile of TSOD mice, which could lead to improvement in the liver pathology of these mice. Three mice per group were used. Daily intake of coffee or its components for 16 wk prevented liver lobular inflammation without improving obesity in TSOD mice. Coffee and its components did not repair the altered levels of Gram-positive and Gram-negative bacteria and an increased abundance of Firmicutes in TSOD mice but rather caused additional changes in bacteria in six genera. However, caffeine and chlorogenic acid partially improved the disrupted plasma SCFA profile in TSOD mice, although coffee had no effects. Whether these alterations in the gut microbiome and the plasma SCFA profile might affect the liver pathology of TSOD mice may deserve further investigation.
Asunto(s)
Café/química , Disbiosis/dietoterapia , Ácidos Grasos Volátiles/metabolismo , Inflamación/dietoterapia , Síndrome Metabólico/dietoterapia , Animales , Cafeína/administración & dosificación , Cafeína/química , Ácido Clorogénico/administración & dosificación , Ácido Clorogénico/química , Modelos Animales de Enfermedad , Disbiosis/fisiopatología , Ácidos Grasos Volátiles/química , Microbioma Gastrointestinal/efectos de los fármacos , Humanos , Inflamación/fisiopatología , Hígado/efectos de los fármacos , Hígado/fisiopatología , Síndrome Metabólico/microbiología , Síndrome Metabólico/fisiopatología , Ratones , Ratones Obesos , Obesidad/dietoterapia , Obesidad/fisiopatologíaRESUMEN
BACKGROUND: Metabolic syndrome is one of the most important health issues worldwide. Obesity causes insulin resistance, hyperlipidemia, diabetes, and various diseases throughout the body. The liver phenotype, which is called nonalcoholic steatohepatitis (NASH), frequently progresses to hepatocellular carcinoma. We recently established a new animal model, Tsumura-Suzuki obese diabetic (TSOD) mice, which spontaneously exhibit obesity, diabetes, hyperlipidemia, and NASH with liver nodules. METHODS: We examined the effects of coffee intake on various conditions of the metabolic syndrome using TSOD mice. The daily volume of coffee administered was limited so that it reflected the appropriate quantities consumed in humans. To clarify the effects of the specific components, animals were divided into two coffee-intake groups that included with and without caffeine. RESULTS: Coffee intake did not significantly affect obesity and hyperlipidemia in TSOD mice. In contrast, coffee intake caused various degrees of improvement in the pancreatic beta cell damage and steatohepatitis with liver carcinogenesis. Most of the effects were believed to be caused by a synergistic effect of caffeine with other components such as polyphenols. However, the antifibrotic effects of coffee appeared to be due to the polyphenols rather than the caffeine. CONCLUSIONS: A daily habit of drinking coffee could possibly play a role in the prevention of metabolic syndrome.
Asunto(s)
Café , Células Secretoras de Insulina/efectos de los fármacos , Síndrome Metabólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/prevención & control , Envejecimiento , Animales , Cafeína/uso terapéutico , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/patología , Diabetes Mellitus Tipo 2/prevención & control , Hiperlipidemias/sangre , Células Secretoras de Insulina/patología , Grasa Intraabdominal/efectos de los fármacos , Grasa Intraabdominal/metabolismo , Hígado/patología , Cirrosis Hepática/patología , Cirrosis Hepática/prevención & control , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/prevención & control , Masculino , Síndrome Metabólico/complicaciones , Ratones , Ratones Obesos , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/patología , Inhibidores de Fosfodiesterasa/uso terapéuticoAsunto(s)
Absceso , Ecocardiografía , Huésped Inmunocomprometido , Nocardiosis , Nocardia , Pericarditis , Pericardio , Tomografía Computarizada por Rayos X , Absceso/diagnóstico por imagen , Absceso/microbiología , Absceso/patología , Anciano de 80 o más Años , Femenino , Humanos , Nocardiosis/diagnóstico por imagen , Nocardiosis/patología , Pericarditis/diagnóstico por imagen , Pericarditis/microbiología , Pericarditis/patología , Pericardio/diagnóstico por imagen , Pericardio/microbiología , Pericardio/patologíaRESUMEN
We previously reported that Tsumura-Suzuki obese diabetic (TSOD) mice, a polygenic model of spontaneous type 2 diabetes, is a valuable model of hepatic carcinogenesis via non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). One of the characteristics of tumors in these mice is the diffuse expression of glutamine synthetase (GS), which is a diagnostic marker for hepatocellular carcinoma (HCC). In this study, we performed detailed histopathological examinations and found that GS expression was diffusely positive in >70% of the hepatic tumors from 15-month-old male TSOD mice. Translocation of ß-catenin into nuclei with enhanced membranous expression also occurred in GS-positive tumors. Small lesions (<1 mm) in GS-positive cases exhibited dysplastic nodules, with severe nuclear atypia, whereas large lesions (>3 mm) bore the characteristics of human HCC, exhibiting nuclear and structural atypia with invasive growth. By contrast, the majority of GS-negative tumors were hepatocellular adenomas with advanced fatty change and low nuclear grade. In GS-negative tumors, loss of liver fatty acid-binding protein expression was observed. These results suggest that the histological characteristics of GS-positive hepatic tumors in TSOD mice resemble human HCC; thus, this model may be a useful tool in translational research targeting the NAFLD/NASH-HCC sequence.
RESUMEN
Among the many potential etiologies for rapidly progressive dementia (RPD), primary central nervous system extranodal NK/T-cell lymphoma, nasal-type (ENKL) is a rare entity. We present the first reported case of autopsy-proven RPD due to ENKL without any mass or enhancing lesion of the brain. A 54-year-old immunocompetent man presented with RPD, myoclonus and ataxia. The mini-mental state examination (MMSE) score was 22/30. His brain MRI revealed progressive brain atrophy without gadolinium enhancement or mass lesion. Five months after the initial evaluation, cognitive impairment further worsened with an MMSE score of 3/30. At the advanced stage, lumbar MRI showed swollen cauda equina with gadolinium enhancement. The number of Epstein-Barr virus (EBV) DNA in cerebrospinal fluid had gradually increased. Twelve months after onset, the patient died of respiratory failure. Pathological findings revealed that lymphoma cells had diffusely invaded the meninges, parenchyma of the brain, spinal cord and cauda equina. Cells were positive for CD3, CD56 and EBV-encoded small RNAs and negative for CD20. No evidence of malignancy was identified in the visceral organs. This report indicates that ENKL should be recognized as one of the rare causes of RPD. Early testing for EBV-DNA in cerebrospinal fluid and imaging of cauda equina would be useful diagnostic tools.
Asunto(s)
Neoplasias Encefálicas/diagnóstico por imagen , Demencia/etiología , Linfoma Extranodal de Células NK-T/complicaciones , Linfoma Extranodal de Células NK-T/diagnóstico , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Neoplasias Encefálicas/complicaciones , Cauda Equina/diagnóstico por imagen , Cauda Equina/patología , Progresión de la Enfermedad , Humanos , Inmunocompetencia , Linfoma Extranodal de Células NK-T/patología , Masculino , Persona de Mediana Edad , Médula Espinal/diagnóstico por imagen , Médula Espinal/patologíaRESUMEN
Variability in antidepressant response is due to genetic and environmental factors. Among genetic factors, the ones controlling for availability of the drug at the target site are interesting candidates. Rs6295C/G SNP in the 5-HT1A gene (HTR1A) has been found to affect the expression and function of HTR1A. In fact rs6295C/G is in strong linkage disequilibrium with other polymorphisms of HTR1A suggesting that those functional effects could be associated with polymorphisms other than or together with the synonymous rs6295C/G. In the present study we examined the possible association of a panel of markers in strong linkage disequilibrium of the HTR1A with SSRI/SNRI response in 137 Japanese major depression subjects followed for 6 weeks. We observed a significant association of better response to antidepressant in rs10042486C/C (P < 0.0001), rs6295G/G (P < 0.0001) and rs1364043T/T (P = 0.018) genotype carriers (minor allele homozygotes), independently from clinical variables. Furthermore minor allele homozygous carriers in all these three SNPs were associated with treatment response by various assessment such as HAM-D score change over time (P = 0.001), week 2 (P < 0.0001), 4 (P = 0.007), and 6 (P = 0.048) as well as response rate (P = 0.0005) and remission rate (P = 0.004). We also pointed out the genotyping mis-definition of rs6295C/G in the previous four articles. In conclusion, this is the first study that reports a significant association of antidepressant response with rs10042486C/T and rs1364043T/G variants of HTR1A and also with rs10042486-rs6295-rs1364043 combination. This finding adds an important information for the pathway of detecting the genetics of antidepressant response even if results must be verified on larger samples.