Assuntos
Malformações Arteriovenosas/complicações , Endoscopia Gastrointestinal , Síndrome do Hamartoma Múltiplo/diagnóstico , Síndrome do Hamartoma Múltiplo/patologia , Pólipos Intestinais/complicações , Intestino Delgado/irrigação sanguínea , Idoso , Feminino , Síndrome do Hamartoma Múltiplo/complicações , Síndrome do Hamartoma Múltiplo/genética , Humanos , Mutação , PTEN Fosfo-Hidrolase/genéticaRESUMO
BACKGROUND: Simultaneous use of proton pump inhibitors (PPIs) has been shown to increase the risk of nonsteroidal anti-inflammatory drug (NSAID)-induced small bowel injury. AIM: To investigate whether polymorphisms of the cytochrome P450 2C19 gene (CYP2C19), encoding a key metabolising enzyme for PPIs, are associated with small bowel injury induced by celecoxib in combination with the PPI rabeprazole. METHODS: Study participants included 55 healthy Japanese volunteers, who participated in the PPI-NSAID Kyushu University Study using video capsule endoscopy. For 2 weeks, 26 subjects were treated with celecoxib plus rabeprazole (rabeprazole group), and 29 subjects received celecoxib plus placebo (placebo group). All subjects were genotyped for CYP2C19 using real-time fluorescent polymerase chain reaction. Subjects were sub-classified as poor metabolizers or extensive metabolizers. The incidence and number of small bowel injuries were compared between poor metabolizers and extensive metabolizers in each group. RESULTS: In the rabeprazole group, the incidence of small bowel injuries was significantly higher in poor metabolizers than in extensive metabolizers (85.7% vs 31.6%, P=.026). The number of mucosal injuries in the rabeprazole group was also significantly higher in poor metabolizers compared with extensive metabolizers (median [range] 3 [0-31] vs 0 [0-7], P=.01). In addition, we found a significant interaction between CYP2C19 genotype and concomitant use of rabeprazole in subjects at risk for celecoxib-induced small bowel injury. CONCLUSIONS: The CYP2C19 genotype might be associated with the risk of small bowel injury when celecoxib is combined with rabeprazole.
Assuntos
Celecoxib/efeitos adversos , Citocromo P-450 CYP2C19/genética , Inibidores da Bomba de Prótons/administração & dosagem , Rabeprazol/administração & dosagem , Adulto , Endoscopia por Cápsula , Método Duplo-Cego , Feminino , Genótipo , Humanos , Enteropatias/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Adulto JovemRESUMO
Previous studies have suggested that the human leukocyte antigen (HLA) is involved in the etiology of Crohn's disease (CD); however, few reports are available on the association between HLA class I antigens and CD in Japan. In this study, we performed association analysis of HLA class I antigens in CD using 208 Japanese patients and 384 healthy controls. We identified novel positive associations between CD and HLA-A*02:01 (odds ratio (OR)=1.64, P=0.016) and HLA-A*02:07 (OR=2.31, P=0.0067) and confirmed previously reported positive associations between CD and HLA-Cw*14:02 (OR=2.18, P=0.0021) and HLA-B*51:01 (OR=1.70, P=0.033). We also identified novel negative associations between CD and HLA-A*24:02 (OR=0.60, P=0.0047) and HLA-B*07:02 (OR=0.38, P=0.0041). Although the associations were not significant after full Bonferroni correction, we suggested that HLA class I genes have dual functions, susceptibility and resistance in controlling the development of CD.
Assuntos
Doença de Crohn/genética , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígenos HLA-C/genética , Povo Asiático/genética , Estudos de Casos e Controles , Genes MHC Classe I , Humanos , JapãoAssuntos
Endoscópios Gastrointestinais , Neoplasias Intestinais/diagnóstico , Linfoma Folicular/diagnóstico , Idoso , Biomarcadores Tumorais/análise , Biópsia , Diagnóstico Diferencial , Feminino , Humanos , Mucosa Intestinal/patologia , Neoplasias Intestinais/patologia , Pólipos Intestinais/diagnóstico , Pólipos Intestinais/patologia , Linfoma Folicular/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de NeoplasiasRESUMO
BACKGROUND AND STUDY AIM: The aim of this study was to elucidate the risk factors for local recurrence after endoscopic mucosal resection (EMR) treatment for superficial esophageal cancer (SEC). PATIENTS AND METHODS: We performed a retrospective analysis of the clinical course of 62 patients with 64 SECs that were treated by EMR between 1993 and 2004. Follow-up examinations by chromoscopy with iodine solution and biopsy were performed 3 months, 6 months, 12 months, and then annually after EMR. Local recurrence was defined as a histologically confirmed finding of cancer cells at the site of the preceding EMR. The contributions of lesion-related and procedure-related factors to local recurrence were analyzed retrospectively. RESULTS: Local recurrence was detected in 14/64 SECs 3-36 months after EMR. Of the lesion-related factors we assessed, local recurrence was found to be more frequent in SECs with a larger diameter (P = 0.01), larger circumferential spread (P = 0.04), or deeper invasion (P = 0.04), although the last two factors failed to demonstrate statistical significance after correction for multiple testing. Piecemeal resection did not increase the risk of local recurrence (P = 0.11), but the need for adjunctive coagulation therapy was found to increase the risk of local recurrence (P = 0.06). CONCLUSIONS: Larger SECs are associated with a higher risk of local recurrence after EMR. In patients with residual lesions, coagulation therapy does not seem to be adequate as additional endoscopic treatment.