RESUMO
BACKGROUND AND AIMS: Gallbladder cancer (GBC) is a neglected disease with substantial geographical variability: Chile shows the highest incidence worldwide, while GBC is relatively rare in Europe. Here, we investigate the causal effects of risk factors considered in current GBC prevention programs as well as C-reactive protein (CRP) level as a marker of chronic inflammation. APPROACH AND RESULTS: We applied two-sample Mendelian randomization (MR) using publicly available data and our own data from a retrospective Chilean and a prospective European study. Causality was assessed by inverse variance weighted (IVW), MR-Egger regression, and weighted median estimates complemented with sensitivity analyses on potential heterogeneity and pleiotropy, two-step MR, and mediation analysis. We found evidence for a causal effect of gallstone disease on GBC risk in Chileans (P = 9 × 10-5 ) and Europeans (P = 9 × 10-5 ). A genetically elevated body mass index (BMI) increased GBC risk in Chileans (P = 0.03), while higher CRP concentrations increased GBC risk in Europeans (P = 4.1 × 10-6 ). European results suggest causal effects of BMI on gallstone disease (P = 0.008); public Chilean data were not, however, available to enable assessment of the mediation effects among causal GBC risk factors. CONCLUSIONS: Two risk factors considered in the current Chilean program for GBC prevention are causally linked to GBC risk: gallstones and BMI. For Europeans, BMI showed a causal effect on gallstone risk, which was itself causally linked to GBC risk.
Assuntos
Índice de Massa Corporal , Proteína C-Reativa/análise , Neoplasias da Vesícula Biliar/etiologia , Cálculos Biliares/complicações , Adulto , Fatores Etários , Chile/epidemiologia , Europa (Continente)/epidemiologia , Feminino , Neoplasias da Vesícula Biliar/epidemiologia , Neoplasias da Vesícula Biliar/genética , Cálculos Biliares/epidemiologia , Predisposição Genética para Doença/genética , Variação Genética , Humanos , Masculino , Análise da Randomização Mendeliana , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: The first large-scale genome-wide association study of gallbladder cancer (GBC) recently identified and validated three susceptibility variants in the ABCB1 and ABCB4 genes for individuals of Indian descent. We investigated whether these variants were also associated with GBC risk in Chileans, who show the highest incidence of GBC worldwide, and in Europeans with a low GBC incidence. METHODS: This population-based study analysed genotype data from retrospective Chilean case-control (255 cases, 2042 controls) and prospective European cohort (108 cases, 181 controls) samples consistently with the original publication. RESULTS: Our results confirmed the reported associations for Chileans with similar risk effects. Particularly strong associations (per-allele odds ratios close to 2) were observed for Chileans with high Native American (=Mapuche) ancestry. No associations were noticed for Europeans, but the statistical power was low. CONCLUSION: Taking full advantage of genetic and ethnic differences in GBC risk may improve the efficiency of current prevention programs.
Assuntos
Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Neoplasias da Vesícula Biliar/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Chile/epidemiologia , Europa (Continente)/epidemiologia , Feminino , Neoplasias da Vesícula Biliar/epidemiologia , Estudos de Associação Genética , Humanos , Indígenas Sul-Americanos/genética , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , População Branca/genéticaRESUMO
Background: Granulomatous lesions occur in tuberculosis (TB), other infections, toxic, allergic, and autoimmune diseases among others. In absence of a an acid-fast bacilli (AFB) confirmation of TB is necessary. Objective: To assess the efficacy of PCR for TB detection and to correlate with granuloma histology and AFB staining. Methods: We analyzed 380 fixed paraffin-embedded tissues (PETs) of granulomas with and without caseous necrosis; suppurative; sarcoidal; or of chronic nonspecific nature. Nested PCR-IS6110 for Mycobacterium tuberculosis complex (MTB) and a nested pan-Mycobacterium for the hsp65 gene were used for Mycobacterium spp detection. Results: PCR was more sensitive than AFB staining for all five catageories of granulomas: G1: PCR 71%, AFB staining 28%. G2: PCR 37%, AFB 8%. G3: PCR 17%, AFB staining 7%. G4: PCR 8%, AFB staining 4%. G5: PCR 6%, AFB staining 0%. Conclusions: Molecular diagnosis of TB using PCR-based testing is a fast, efficacious and sensitive method that increased the accuracy of PET histological diagnosis associated with granulomatous lesions.
Introducción: Lesiones granulomatosas ocurren en tuberculosis (TBC), otras infecciones, condiciones tóxicas, alérgicas y autoinmunes, entre otras. Con baciloscopia negativa, es necesario confirmar el diagnóstico de TBC. Objetivo: Evaluar la eficacia de la RPC para detectar TBC comparado con baciloscopia en relación a la histología del granuloma. Métodos: Analisis de 380 tejidos fijados en formalina e incluidos en parafina (TFFP) con diferentes tipos de granulomas: con necrosis caseosa; sin necrosis caseosa; supurativo; sarcoidal; a cuerpo extraño/inespecífico. Utilizamos RPC anidada-IS6110 para detección del complejo Mycobacterium tuberculosis (MTB) y una pan-RPC anidada-hsp65 para Mycobacterium spp. Resultados: La detección de TBC mediante RPC fue significativamente superior a baciloscopia en los cinco tipos de granuloma: G1: RPC 71%, baciloscopia 28%; G2: RPC 37%, baciloscopia 8%; G3: RPC 17%, baciloscopia 7%; G4: RPC 8%, baciloscopia 4%; G5: RPC 6%, baciloscopia 0%. Conclusión: El diagnóstico de TBC por RPC es un método rápido, eficaz y de gran sensibilidad, que aumenta la precisión del diagnóstico diferencial de lesiones granulomatosas de TFFP procesados rutinariamente en histopatología.
Assuntos
Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Adulto Jovem , DNA Bacteriano/genética , Granuloma/microbiologia , Mycobacterium tuberculosis/genética , Tuberculose/diagnóstico , Diagnóstico Diferencial , Formaldeído , Granuloma/diagnóstico , Inclusão em Parafina , Reação em Cadeia da Polimerase , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Coloração e Rotulagem , Fixação de TecidosRESUMO
BACKGROUND: Granulomatous lesions occur in tuberculosis (TB), other infections, toxic, allergic, and autoimmune diseases among others. In absence of a an acid-fast bacilli (AFB) confirmation of TB is necessary. OBJECTIVE: To assess the efficacy of PCR for TB detection and to correlate with granuloma histology and AFB staining. METHODS: We analyzed 380 fixed paraffin-embedded tissues (PETs) of granulomas with and without caseous necrosis; suppurative; sarcoidal; or of chronic nonspecific nature. Nested PCR-IS6110 for Mycobacterium tuberculosis complex (MTB) and a nested pan-Mycobacterium for the hsp65 gene were used for Mycobacterium spp detection. RESULTS: PCR was more sensitive than AFB staining for all five catagories of granulomas: G1: PCR 71%, AFB staining 28%. G2: PCR 37%, AFB 8%. G3: PCR 17%, AFB staining 7%. G4: PCR 8%, AFB staining 4%. G5: PCR 6%, AFB staining 0%. CONCLUSIONS: Molecular diagnosis of TB using PCR-based testing is a fast, efficacious and sensitive method that increased the accuracy of PET histological diagnosis associated with granulomatous lesions.
Assuntos
DNA Bacteriano/genética , Granuloma/microbiologia , Mycobacterium tuberculosis/genética , Tuberculose/diagnóstico , Adolescente , Adulto , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Formaldeído , Granuloma/diagnóstico , Humanos , Lactente , Masculino , Inclusão em Parafina , Reação em Cadeia da Polimerase , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Coloração e Rotulagem , Fixação de Tecidos , Adulto JovemRESUMO
We report on a patient who presented to ENT services with right side epistaxis, frontal lobe headache, right infraorbital pain and the feeling of having a stuffy nose. CT and MRI were performed and later a biopsy confirmed the presence of sinonasal plasmocytoma. The Head and Neck oncology committee recommended radiotherapy as the choice of treatment. At the present time the patient is being followed on scheduled medical visits.
Se reporta el caso de un paciente que se presentó en el servicio de Otorrinolaringología con epistaxis, cefalea del lóbulo frontal derecho, dolor infraorbitario derecho y la sensación de tener la nariz tapada. Se realizaron TC y RNM, y luego una biopsia confirmó la presencia de un plasmocitoma nasosinusal. El comité de oncología de cabeza y cuello recomendó radioterapia como tratamiento de elección. En la actualidad, el paciente está en siguimiento y control en las visitas médicas regulares.
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Imageamento por Ressonância Magnética , Neoplasias Nasais/diagnóstico , Plasmocitoma/diagnóstico , Tomografia Computadorizada por Raios X , Neoplasias Nasais/radioterapia , Plasmocitoma/radioterapiaRESUMO
We report on a patient who presented to our clinic with a volume increase and pain at left maxillary region. A biopsy of the area was performed and the lesion was diagnosed as differentiated squamous cell carcinoma of the type cuniculatum. Due to the size of the tumor and compromise of vital intracraneal structures it was decided to perform surgical drainage and later is evaluated because of the tumor persistence to ultimately use palliative care...
Se presenta a una paciente que acudió a nuestra clínica con un aumento de volumen y dolor en región maxilar izquierda. Se realizó una biopsia del área y la lesión fue diagnosticada como carcinoma de células escamosas diferenciado de tipo cuniculatum. Debido al tamaño del tumor y el compromiso de estructuras intracraneales vitales, se decidió realizar un drenaje quirúrgico y posteriormente se evalúa la causa de la persistencia del tumor para finalmente entregar cuidados paliativos...
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/diagnóstico , Neoplasias dos Seios Paranasais/cirurgia , Neoplasias dos Seios Paranasais/diagnóstico , Biópsia , Tomografia Computadorizada por Raios XRESUMO
We report on a patient who presented at our clinic with a growth of the right palate of twenty years duration. A biopsy of the area was performed and the lesion was diagnosed as low-grade mucoepidermoid carcinoma (MEC). Due to the size of the tumor, it was decided to begin treatment with radiotherapy followed by chemotherapy. Once the initial treatment was completed, the lesion was reevaluated and surgery followed by reconstruction was recommended. The Patient rejected the recommended treatment and opted to enrolled in a pain management, palliative care program.
Reportamos sobre un paciente que se presentó con un crecimiento del paladar derecho de veinte años de evolución. Se realizó una biopsia del área y se diagnosticó la lesión como carcinoma mucoepidermoide (MEC) bajo grado. Debido al tamaño del tumor, se decidió comenzar el tratamiento con radioterapia seguida de quimioterapia. Una vez que el tratamiento inicial se completó, la lesión fue reevaluada y se recomendó la cirugía seguida de reconstrucción. El paciente rechazó el tratamiento recomendado y optó por seguir un tratamiento de manejo del dolor, programa de cuidados paliativos.