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1.
Inflamm Bowel Dis ; 29(11): 1730-1740, 2023 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-36626567

RESUMO

BACKGROUND: This nationwide prospective registry study investigated the real-world effectiveness, safety, and persistence of vedolizumab (VDZ) in inflammatory bowel disease (IBD) patients in Taiwan. Disease relapse rates after VDZ discontinuation due to reimbursement restriction were assessed. METHODS: Data were collected prospectively (January 2018 to May 2020) from the Taiwan Society of IBD registry. RESULTS: Overall, 274 patients (147 ulcerative colitis [UC] patients, 127 Crohn's disease [CD] patients) were included. Among them, 70.7% with UC and 50.4% with CD were biologic-naïve. At 1 year, 76.0%, 58.0%, 35.0%, and 62.2% of UC patients and 57.1%, 71.4%, 33.3%, and 30.0% of CD patients achieved clinical response, clinical remission, steroid-free remission, and mucosal healing, respectively. All patients underwent hepatitis B and tuberculosis screening before initiating biologics, and prophylaxis was recommended when necessary. One hepatitis B carrier, without antiviral prophylaxis due to economic barriers, had hepatitis B reactivation during steroid tapering and increasing azathioprine dosage, which was controlled with an antiviral agent. No tuberculosis reactivation was noted. At 12 months, non-reimbursement-related treatment persistence rates were 94.0% and 82.5% in UC and CD patients, respectively. Moreover, 75.3% of IBD patients discontinued VDZ due to mandatory drug holiday. Relapse rates after VDZ discontinuation at 6 and 12 months were 36.7% and 64.3% in CD patients and 42.9% and 52.4% in UC patients, respectively. CONCLUSIONS: The findings demonstrated VDZ effectiveness in IBD patients in Taiwan, with high treatment persistence rates and favorable safety profiles. A substantial IBD relapse rate was observed in patients who had mandatory drug holiday.


Assuntos
Colite Ulcerativa , Doença de Crohn , Hepatite B , Doenças Inflamatórias Intestinais , Humanos , Taiwan , Indução de Remissão , Fármacos Gastrointestinais/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Recidiva , Resultado do Tratamento , Estudos Retrospectivos
2.
J Formos Med Assoc ; 122(7): 549-556, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36443148

RESUMO

BACKGROUND: Purpose: Anemia affects the life quality of inflammatory bowel disease (IBD) patients, but no report from Asian about anemia screening and its impact previously. We aimed to explore the prevalence and impact of anemia among the IBD patients in Taiwan. METHODS: A retrospective study was conducted from January 2006 to February 2018 at National Taiwan University Hospital. Clinical characteristics and outcomes were analyzed. RESULTS: A total of 1604 IBD patients were enrolled [494 Crohn's disease (CD) and 1110 ulcerative colitis (UC)]. Overall, 95.3% (471/494) of CD and 87.9% (976/1110) of UC patients underwent anemia screening. Anemia screening rate in IBD patients significantly increased from 62.6% (162/259) in 2006 to 77.2% (838/1086) in 2017. The mean time from IBD diagnosis to anemia screening was 122.4 days in CD patients and even longer in UC patients at 216.2 days. Persistent anemia was found in 47.3% (548/1158) of the screened patients. Risk factors of persistent anemia included low body mass index [odds ratio (OR) = 1.96, p < 0.01], steroid [OR = 2.96, p < 0.01], thiopurine [OR = 2.62, p < 0.01], colectomy [OR = 6.3, p < 0.01], and small bowel resection [OR = 3.21, p < 0.05)] after IBD diagnosis. Compared with those without anemia, anemic IBD patients had higher admission (p < 0.01) and mortality rates (p < 0.01). CONCLUSION: The anemia screening rate was acceptable and increased over time in Taiwan. Since anemia is associated with worse outcomes, earlier survey and treatment of anemia in IBD patients is recommended.


Assuntos
Anemia , Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Humanos , Estudos Retrospectivos , Doenças Inflamatórias Intestinais/complicações , Colite Ulcerativa/complicações , Colite Ulcerativa/epidemiologia , Doença de Crohn/complicações , Anemia/etiologia , Anemia/complicações
3.
BMC Gastroenterol ; 22(1): 173, 2022 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-35395754

RESUMO

BACKGROUND: Primary signet ring cell carcinoma of the colon and rectum (PSRCCR) is rare, usually diagnosed at advanced stage with poor outcomes. We aimed to find possible diagnostic clues in order to help diagnosis. METHODS: A retrospective study of PSRCCR patients from 1993 to 2018 was reviewed at a single tertiary center. Colorectal adenocarcinoma patients as control group with 1:4 ratio was also enrolled. RESULTS: 18 patients with PSRCCR were identified. The prevalence rate was 0.16% (18 of 11,515). The mean age was 50.2 years-old in PSRCCR group and 63 years-old in non-SRCC colorectal cancer patients (p < 0.001). Diagnosis tool depends on colonoscopy were much less in PSRCCR group than control group (44.4% vs 93%, p < 0.001). SRCC patients had higher level of CEA (68.3 vs 17.7 ng/mL, p = 0.004) and lower level of Albumin (3.4 vs 4.3 g/dL, p < 0.001). The majority of PSRCCR tumor configuration was ulcerative and infiltrative. More PSRCCR pathology presented as high-grade carcinoma (66.7 vs 1.4%, p < 0.001) and lymphovascular invasion (77.8 vs 44.4%, p = 0.011) than control group. More PSRCCR patients were diagnosed at advanced stage (88.8 vs 40.3%, p = 0.001). Higher mortality was also noticed in PSRCCR group than control group (72.2 vs 20.8%, p < 0.001). CONCLUSION: For young patients with long segment colonic stenosis and ulcerative/ infiltrative mucosa but endoscopic biopsy failed to identify malignant cells, earlier operation or non-colon site biopsy is suggested for diagnosing the PSRCCR.


Assuntos
Carcinoma de Células em Anel de Sinete , Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Retais , Carcinoma de Células em Anel de Sinete/patologia , Estudos de Casos e Controles , Neoplasias do Colo/epidemiologia , Neoplasias do Colo/patologia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Neoplasias Retais/epidemiologia , Neoplasias Retais/patologia , Reto/patologia , Estudos Retrospectivos
4.
Intest Res ; 20(2): 224-230, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35124955

RESUMO

BACKGROUND/AIMS: Primary sclerosing cholangitis (PSC) is associated with inflammatory bowel disease (IBD). We aimed to evaluate the prevalence, clinical manifestation, and outcomes of PSC in Taiwanese patients with IBD. METHODS: This retrospective study enrolled patients with IBD admitted from January 1, 1996, to December 31, 2018, to National Taiwan University Hospital. A case-matched analysis was performed comparing patients with IBD with and without PSC according to age, sex, and time of admission, with ratios of 1:4 and 1:2 in the adult and pediatric groups, respectively. RESULTS: In total, 763 patients with IBD were enrolled, 12 of whom were also diagnosed with PSC (1.57%). All these patients had ulcerative colitis (UC). A greater incidence of IBD with PSC was observed in younger patients than in older patients. Male sex was a risk factor for PSC in pediatric patients with IBD (P=0.015); 75% of these patients were diagnosed with PSC along with or after the diagnosis of UC. There was no significant difference in colitis extent and severity between the groups; however, a higher proportion of rectal sparing was observed in patients with PSC (P=0.001). There was no significant difference in cancer development between the groups (P=0.679). CONCLUSIONS: A 1.57% prevalence of PSC was observed in Taiwanese patients with IBD. The majority of patients with IBD and PSC were men and were diagnosed at a younger age. Hence, routine evaluation of biliary enzymes and liver imaging is recommended in young male patients with IBD.

5.
J Transl Med ; 17(1): 414, 2019 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-31831015

RESUMO

BACKGROUND: Inflammatory bowel disease (IBD) was emerging as a worldwide epidemic disease, and the advanced therapy changed the clinical course and possibly the outcomes. Our previous study reported a higher mortality rate from (IBD) in Taiwan than in Western countries. We proposed to analyze the trend and risk factors of mortality in order to improve the care quality of IBD patients. METHODS: This retrospective study was conducted to analyze data for January 2001 to December 2015 from a registered database, compiled by the Taiwan's National Health Insurance. RESULTS: Between 2001 and 2015, a total of 3806 IBD patients [Crohn's disease (CD): 919; ulcerative colitis (UC): 2887] were registered as having catastrophic illness, and 8.2% of these patients died during follow-up. The standardized mortality ratios (SMRs) of CD and UC were 3.72 (95% CI 3.02-4.55) and 1.44 (95% CI 1.26-1.65), respectively, from 2001 to 2015, respectively. A comparison of the periods of 2011-2015 and 2001-2005 revealed a decrease in the mortality rates from both UC and CD. Multivariate Cox proportional hazards analysis identified elderly individuals; sepsis and pneumonia were the risk factors for IBD mortality. The specific risk factors of mortality were liver cancer for UC and surgeries for CD. CONCLUSION: For further decreasing IBD-related mortality in Taiwan, we need to pay special attention toward elderly individuals, infection control, cancer screening and improvement in perioperative care.


Assuntos
Doenças Inflamatórias Intestinais/mortalidade , Adulto , Fatores Etários , Colite Ulcerativa/mortalidade , Doença de Crohn/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Sistema de Registros , Fatores de Risco , Taxa de Sobrevida , Taiwan/epidemiologia
6.
Scand J Gastroenterol ; 54(4): 506-512, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30978145

RESUMO

Objectives: The clinical impact of endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) in managing pancreatic cystic neoplasms (PCNs) remains controversial. The aim of this study was to identify which patients with PCNs would benefit from EUS-FNA. Methods: A retrospective study was performed on patients with PCNs who underwent EUS-FNA between January 2009 and June 2018. A discordant or a consistent diagnosis after EUS-FNA was analyzed and was correlated with the clinical demographic data and cystic features. Predictors of the change in the diagnosis after EUS-FNA were analyzed. Results: One hundred eighty-eight cases of PCNs were analyzed. EUS-FNA changed the diagnosis in 45.7% of all patients with PCNs and 54.5% patients with presumed branch ductal type intraductal papillary mucinous neoplasm (BD-IPMN) and impacted the recommendation in 35.6% of patients with PCNs and 50.5% patients with BD-IPMN. Patients with a discordant diagnosis after EUS-FNA were younger in age (54.8 ± 12.6 vs. 61.2 ± 14.2; p=.037) and had a cyst size larger than 3 cm than patients with a consistent diagnosis after EUS-FNA. The only worrisome feature (WF) that differed between patients with a discordant and a consistent diagnosis after EUS-FNA was the main pancreatic duct (MPD) between 5 and 9 mm (p=.013). In multivariate analysis, a cyst size >3 cm and age were independent predictors of diagnostic changes after EUS-FNA (OR: 5.33, 95% CI: 1.79-15.88, p = .003; OR: 0.96, 95% CI: 0.93-0.99, p = .031). Conclusions: EUS-FNA made a significant change in the management of nearly half of the patients with PCNs, especially in younger patients and in patients with a cyst size larger than 3 cm.


Assuntos
Fatores Etários , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Cisto Pancreático/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Adulto , Idoso , Endossonografia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Cisto Pancreático/patologia , Neoplasias Pancreáticas/patologia , Pseudocisto Pancreático/diagnóstico , Pseudocisto Pancreático/patologia , Estudos Retrospectivos , Taiwan
7.
J Clin Med ; 7(11)2018 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-30373275

RESUMO

BACKGROUND: No nationwide, long-term follow-up study has assessed medication-associated outcomes for Asian patients with inflammatory bowel disease (IBD). This study examined medication-associated outcomes for Taiwanese patients with IBD. METHODS: In this nationwide cohort study, 3806 patients who had received catastrophic illness registration for IBD from 2001 to 2015 were enrolled. RESULTS: A higher accumulated dosage of 5-aminosalicylic acid (5-ASA) was associated with decreased risks of hospitalization (hazard ratio (HR) = 0.6) and operation (HR = 0.5). Thiopurine was associated with increased risks of hospitalization (HR = 2.1 in the high-dosage group) and tuberculosis (TB; HR = 3.6) reactivation but not with operation risk. A higher accumulated dosage of anti-TNF-α agents was associated with increased risks of hospitalization (HR = 3.3), operation (HR = 2.9), hepatitis B (HR = 4.3), and TB (HR = 5.1) reactivation. Corticosteroids were associated with increased risks of hospitalization (HR = 3.5 in the high-dosage group), risk of operation, hepatitis B (HR = 2.8) and TB (HR = 2.8) reactivation. CONCLUSIONS: 5-ASA usage is associated with decreased risks of hospitalization and operation for patients with IBD, whereas thiopurine, corticosteroids, and anti-TNF-α agents are associated with increased risks of hospitalization and hepatitis B and TB reactivation.

8.
Biomed Microdevices ; 20(1): 3, 2017 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-29164403

RESUMO

This study aimed to investigate the drug delivery efficacy and bio-effectiveness of a novel photodynamic therapy (PDT)-matrix drug delivery system for cholangiocarcinoma (CCA). Metallic stents were coated with polyurethane (PU) as the first layer. A 2-hydroxyethyl methacrylate (2-HEMA)/ethylene glycol dimethacrylate (EGDMA)/benzoyl peroxide (BPO) layer and a poly(ethylene-co-vinyl acetate) (PEVA)/poly(n-butyl methacrylate) (PBMA)/polyvinylpyrrolidone K30 (K30) layer containing various concentrations of Photofrin were then incorporated onto the stent as the second and third layers. After incubating the layered membranes with cultured CCA cell line, the release of Photofrin, cell viability, the intracellular uptake of Photofrin, reactive oxygen species (ROS) generation, and apoptosis were determined. Using a single-layer diffusion model, the maximum release of Photofrin from the 5 to 10% K30 formulas was 80 and 100%, respectively, after 24 h. When using the multiple-layer diffusion model, the released Photofrin showed an initial burst of the loading dose from the PEVA/PBMA/K30 layer. In the immobilized model, less than 5% of the Photofrin from the 2-HEMA/EGDMA/BPO layer was released over the 24-h period. Cell viability decreased linearly with increasing Photofrin concentrations, and ROS generation and apoptosis were shown to increase significantly with increasing Photofrin concentrations, until the concentration of Photofrin reached a saturation point of 1.5 µg/ml. This new, multiple-layered, PDT-based stent with dual-release mechanisms is a promising treatment for CCA and cancer-related ductal stenosis.


Assuntos
Neoplasias dos Ductos Biliares/tratamento farmacológico , Colangiocarcinoma/tratamento farmacológico , Éter de Diematoporfirina/administração & dosagem , Sistemas de Liberação de Medicamentos/instrumentação , Fotoquimioterapia/métodos , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Apoptose/efeitos dos fármacos , Neoplasias dos Ductos Biliares/metabolismo , Neoplasias dos Ductos Biliares/patologia , Linhagem Celular Tumoral , Colangiocarcinoma/metabolismo , Colangiocarcinoma/patologia , Éter de Diematoporfirina/farmacocinética , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Stents Farmacológicos , Humanos , Metacrilatos/química , Fotoquimioterapia/instrumentação , Ácidos Polimetacrílicos/química , Polivinil/química , Espécies Reativas de Oxigênio/metabolismo
9.
Inflamm Bowel Dis ; 23(10): 1730-1740, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28906292

RESUMO

BACKGROUND: The integrity of the gut barrier in patients with inflammatory bowel disease is known to be impaired but the exact mechanisms remain mostly unknown. SHANK3 mutations are associated with autism, and patients with autism are known to have higher proportions of inflammatory bowel disease. Here, we explore the role of SHANK3 in inflammatory bowel disease, both in vivo and in vitro. METHODS: Dextran sulfate sodium colitis was induced in SHANK3 knockout mice. Transepithelial electrical resistance, paracellular permeability, and Salmonella invasion assays were used to evaluate epithelial barrier function, in vitro and in vivo. Expression of tight junction proteins, protein kinases, and MAP kinase phosphorylation changes were analyzed by immunoblotting after overexpression or knockdown of SHANK3 expression. SHANK3 expression in intestinal tissue from patients with Crohn's disease was analyzed by quantitative polymerase chain reaction and immunohistochemistry. RESULTS: SHANK3 knockout mice were more susceptible to dextran sulfate sodium. SHANK3 knockout resulted in a leaky epithelial barrier phenotype, as demonstrated by decreased transepithelial electrical resistance, increased paracellular permeability, and increased Salmonella invasion. Overexpression of SHANK3 enhanced ZO-1 expression, and knockdown of SHANK3 resulted in decreased expression of ZO-1. Regulation of ZO-1 expression by SHANK3 seems to be mediated through a PKCε-dependent pathway. SHANK3 expression correlated with ZO-1 and PKCε in colonic tissue of patients with Crohn's disease. CONCLUSIONS: The expression level of SHANK3 affects ZO-1 expression and the barrier function in intestinal epithelial cells. This may provide novel insights in Crohn's disease pathogenesis and treatment.


Assuntos
Permeabilidade da Membrana Celular/genética , Colite/genética , Doença de Crohn/genética , Proteínas do Tecido Nervoso/genética , Proteína da Zônula de Oclusão-1/genética , Animais , Células CACO-2 , Colite/induzido quimicamente , Colo/patologia , Doença de Crohn/patologia , Sulfato de Dextrana/administração & dosagem , Modelos Animais de Doenças , Células Epiteliais/metabolismo , Células HCT116 , Humanos , Sistema de Sinalização das MAP Quinases , Masculino , Camundongos , Camundongos Knockout , Proteínas dos Microfilamentos , Fosforilação , Proteína Quinase C-épsilon/genética , Salmonella
10.
BMC Gastroenterol ; 17(1): 28, 2017 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-28193173

RESUMO

BACKGROUND: Colitis is exacerbated in patients with concurrent cytomegalovirus (CMV) infection and inflammatory bowel disease (IBD). We assessed the prevalence and clinical features of CMV colitis in hospitalized IBD patients. METHODS: A retrospective study reviewed the data from January 1, 1998 through December 31, 2013 compiled at the National Taiwan University Hospital. The CMV colitis patients' demographic data, clinical information, treatment regimens, pathologic findings, and outcome were analyzed. RESULTS: A total of 673 IBD patients were hospitalized during the study period. There were 312 patients diagnosed with Crohn's disease (CD) and 361 with ulcerative colitis (UC). CMV colitis was diagnosed as having positive inclusion bodies in colonic tissue. Six of the 312 CD patients (1.9%) and five of the 361 UC patients (1.4%) were diagnosed with CMV colitis. Compared to CD patients without CMV colitis, patients with CMV colitis were more often older (p < 0.005). Higher steroid usage was noted in the CMV positive group compared to age and gender matched CMV negative IBD patients (81.8% vs. 51.5%). Eight patients received ganciclovir treatment. Three patients who did not receive antiviral treatment had colitis flare-ups after the index admission. CONCLUSIONS: The prevalence of CMV colitis in hospitalized IBD inpatients was 1.6% in Taiwan. Two associated factors for CMV colitis in hospitalized IBD patients were that they were elderly in CD and were on higher doses of steroids. Routine histopathology studies and/or PCR for refractory colitis patients are suggested to diagnose CMV colitis. Once the diagnosis is made, antiviral treatment is recommended to decrease the colitis relapse rate.


Assuntos
Colite Ulcerativa/virologia , Colite/epidemiologia , Doença de Crohn/virologia , Infecções por Citomegalovirus/epidemiologia , Citomegalovirus , Adolescente , Adulto , Criança , Colite/complicações , Colite/virologia , Colo/virologia , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/virologia , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Encaminhamento e Consulta/estatística & dados numéricos , Estudos Retrospectivos , Taiwan/epidemiologia , Adulto Jovem
11.
Intest Res ; 13(1): 19-26, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25691840

RESUMO

Crohn's disease (CD) is a disease with chronic inflammation of unknown etiology involving any part of the gastrointestinal tract. The incidence and prevalence of CD are increasing recently in Asia. Half of the CD patients will have intestinal complications, such as strictures or fistulas, within 20 years after diagnosis. Twenty-five percentage of CD patients have had at least one small bowel stricture and 10% have had at least one colonic stricture and lead to significant complications. Most of these patients will require at least one surgery during their lifetime. Early diagnosis and evaluation with adequate managements for the patients can prevent disability and mortality of these patient. Here, we reviewed the current incidence of CD with stricture, the etiology of stricture, and how to diagnose and manage the stricture.

12.
World J Gastroenterol ; 21(48): 13566-73, 2015 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-26730169

RESUMO

AIM: To evaluate the correlation between fecal calprotectin (fC), C-reactive protein (CRP), and endoscopic disease score in Asian inflammatory bowel disease (IBD) patients. METHODS: Stool samples were collected and assessed for calprotectin levels by Quantum Blue Calprotectin High Range Rapid test. Crohn's disease endoscopic index of severity (CDEIS) and ulcerative colitis endoscopic index of severity (UCEIS) were used for endoscopic lesion scoring. RESULTS: A total of 88 IBD patients [36 patients with Crohn's disease (CD) and 52 with ulcerative colitis (UC)] were enrolled. For CD patients, fC correlated with CDEIS (r = 0.465, P = 0.005) and CRP (r = 0.528, P = 0.001). fC levels in UC patients correlated with UCEIS (r = 0.696, P < 0.0001) and CRP (r = 0.529, P = 0.0005). Calprotectin could predict endoscopic remission (CDEIS < 6) with 50% sensitivity and 100% specificity (AUC: 0.74) in CD patients when using 918 µg/g as the cut-off. When using 191 µg/g as the cut-off in UC patients, calprotectin could be used for predicting endoscopic remission (UCEIS < 3) with 88% sensitivity and 75% specificity (AUC: 0.87). CONCLUSION: fC correlated with both CDEIS and UCEIS. fC could be used as a predictor of endoscopic remission for Asian IBD patients.


Assuntos
Colite Ulcerativa/metabolismo , Colite Ulcerativa/patologia , Colo/química , Colo/efeitos dos fármacos , Colo/patologia , Colonoscopia , Doença de Crohn/metabolismo , Doença de Crohn/patologia , Fezes/química , Complexo Antígeno L1 Leucocitário/análise , Adolescente , Adulto , Idoso , Povo Asiático , Biomarcadores/análise , Proteína C-Reativa/análise , Colite Ulcerativa/etnologia , Colite Ulcerativa/terapia , Doença de Crohn/etnologia , Doença de Crohn/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Indução de Remissão , Índice de Gravidade de Doença , Taiwan , Resultado do Tratamento , Adulto Jovem
13.
PLoS One ; 9(6): e100515, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24945726

RESUMO

BACKGROUND & AIMS: To date, only one gene (TNFSF15) has been identified and validated as a Crohn's disease (CD)-associated gene in non-Caucasian populations. This study was designed to identify novel CD-associated single nucleotide polymorphisms (SNPs)/genes and to validate candidate genes using a functional assay. METHODS: SNPs from 16 CD patients and 16 age- and sex-matched control patients were analyzed using Illumina platform analysis. Subsequently, we expanded the study and followed 53 CD patients and 41 control patients by Sequenom MassArray analysis. Quantitative PCR and immunohistochemical staining were performed to assess mRNA and protein expression of the candidate gene on tissue isolated from CD patients. Genotype was correlated with CD phenotypes. Finally, the candidate gene was cloned and its effect on NF-κB activity assessed using a reporter luciferase assay. RESULTS: SLCO3A1 (rs207959) reached statistical significance in the first-stage analysis (P = 2.3E-02) and was further validated in the second-stage analysis (P = 1.0E-03). Genotype and phenotype analysis showed that the rs207959 (T) allele is a risk allele that alters SLCO3A1 mRNA expression and is associated with intestinal perforation in CD patients. Higher levels of mRNA and protein expression of SLCO3A1 were seen in CD patients compared with the control group. Overexpression of SLCO3A1 induced increased NF-κB activity and increased phosphorylation of P65, ERK, and JNK. Nicotine augmented the activation of NF-κB in the presence of SLCO3A1. CONCLUSIONS: SLCO3A1, a novel CD-associated gene, mediates inflammatory processes in intestinal epithelial cells through NF-κB transcription activation, resulting in a higher incidence of bowel perforation in CD patients.


Assuntos
Doença de Crohn/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Perfuração Intestinal/genética , NF-kappa B/metabolismo , Transportadores de Ânions Orgânicos/genética , Adolescente , Adulto , Idoso , Alelos , Estudos de Casos e Controles , Criança , Doença de Crohn/complicações , Doença de Crohn/enzimologia , Demografia , Feminino , Células HEK293 , Humanos , Perfuração Intestinal/complicações , Perfuração Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Nicotina/farmacologia , Transportadores de Ânions Orgânicos/metabolismo , Fosforilação/efeitos dos fármacos , Polimorfismo de Nucleotídeo Único/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Adulto Jovem
14.
J Gastroenterol Hepatol ; 29(4): 723-9, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24783249

RESUMO

BACKGROUND AND AIM: Focusing on TNFSF15 instead of NOD2, we set out to evaluate whether combining serologic and genetic markers could distinguish between Crohn's disease (CD) and ulcerative colitis (UC), and whether they could be used to stratify the disease behavior of Taiwanese CD patients. METHODS: Clinical information, serum isolation, and DNA were collected after obtaining informed consent. The serological markers were analyzed by ELISA kits and the genetic analysis for TNFSF15 single-nucleotide polymorphisms (SNPs) by Sequenom. Statistic analyses were conducted by SAS 9.2 (Cary, NC, USA). RESULTS: This study included 108 patients (55 CD, 53 UC) and 60 healthy controls. An initial low positive rate and low sensitivity for the serological markers led us to reset the cut-off values. This reset cut-off for ASCA IgA yielded a sensitivity of 0.291 and specificity of 0.925 for differentiating CD from UC patients. The reset cut-off value for p-ANCA (anti-MPO) had a sensitivity of 0.461 and a specificity of 0.817 for differentiating inflammatory bowel disease patients from healthy controls. Among the TNFSF15 SNPs, rs4263839 associated with CD in Taiwan (P = 0.005), haplotype analysis did not increase the association. Combining the genetic marker TNFSF15 (rs4263839) and serological marker ASCA IgA increased the area under the curve from 0.61 to 0.70 for predicting stenosis/perforating phenotype, compared to ASCA IgA alone. CONCLUSIONS: Serological markers need to be tested and tailored to different countries/ethnicities. Combining the genetic marker TNFSF15 with ASCA IgA increased the power of predicting stenosis/perforating phenotype in CD patients with TNFSF15 but not with a NOD2 genetic background.


Assuntos
Anticorpos Anticitoplasma de Neutrófilos/imunologia , Doença de Crohn/genética , Imunoglobulina A/sangue , Saccharomyces cerevisiae/imunologia , Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral/genética , Adolescente , Adulto , Biomarcadores/sangue , Colite Ulcerativa/genética , Colite Ulcerativa/imunologia , Doença de Crohn/imunologia , Ensaio de Imunoadsorção Enzimática , Marcadores Genéticos , Humanos , Masculino , Pessoa de Meia-Idade , Proteína Adaptadora de Sinalização NOD2/genética , Fenótipo , Polimorfismo de Nucleotídeo Único , Valor Preditivo dos Testes , Taiwan , Adulto Jovem
15.
J Gastroenterol Hepatol ; 29(5): 1119-25, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24372748

RESUMO

BACKGROUND AND AIM: Biliary tract carcinomas (BTCs) are difficult to diagnose and treat. Epidermal growth factor receptor (EGFR) represents a therapeutic target for the BTCs. Mutations of the EGFR gene and the activation of its downstream pathways, including KRAS and BRAF, predict the sensitivity to anti-EGFR treatment. The aims of this study were to analyze the EGFR, KRAS and BRAF mutations in BTCs and their association with clinical outcomes. METHODS: Paraffin-embedded specimens containing 137 BTCs resected at the National Taiwan University Hospital between 1995 and 2004 were analyzed. The exons 18-21 of EGFR gene, the codon 12, 13 and 61 of KRAS gene, and BRAF V600E mutation were analyzed. We examined the correlation between these mutations and the overall survival, tumor location, stage, and differentiation in BTCs. RESULTS: Thirteen (9.5%) BTC patients had EGFR mutations while 23 (16.8%) patients had KRAS mutations. Only one patient had BRAF mutation. Factors influencing survival on univariate analysis were tumor stage, tumor differentiation, and EGFR mutation. On multivariate analysis, EGFR mutation and tumor stage were independent prognostic factors. A correlation between KRAS or BRAF mutations and prognosis was not observed. CONCLUSIONS: EGFR and KRAS mutations are not uncommon in BTCs. BRAF mutation is rare in BTCs. EGFR mutation was an independent prognostic marker in BTCs in addition to tumor stage and differentiation. No simultaneous EGFR and KRAS mutations in extrahepatic cholangiocarcinoma and gallbladder carcinoma were found. EGFR and KRAS mutations should be evaluated when tailoring molecular-targeted therapy to patients with BTCs.


Assuntos
Neoplasias do Sistema Biliar/genética , Neoplasias do Sistema Biliar/patologia , Receptores ErbB/genética , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas/genética , Proteínas ras/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Sistema Biliar/terapia , Transformação Celular Neoplásica/genética , Códon/genética , Éxons/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Estadiamento de Neoplasias , Prognóstico , Proteínas Proto-Oncogênicas p21(ras) , Taiwan
16.
BMC Gastroenterol ; 13: 166, 2013 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-24314308

RESUMO

BACKGROUND: The incidence of the inflammatory bowel diseases (IBD), ulcerative colitis (UC) and Crohn's disease (CD), has been increasing in Asia. We probed the nationwide registered database to assess the incidence, prevalence, gender distribution, age of diagnosis and the survival status of IBD patients in Taiwan. METHODS: A retrospective study was conducted to analyze the registered database compiled by the National Health Insurance provided by the Department of Health, Taiwan, from January 1998 through December 2008. RESULTS: A total of 1591 IBD patients were registered from 1998 to 2008 in Taiwan (CD: 385; UC: 1206). The incidence of CD increased from 0.19/100,000 in 1998 to 0.24/100,000 in 2008. The incidence of UC increased from 0.61/100,000 in 1998 to 0.94/100,000 in 2008. The prevalence of CD increased from 0.19/100,000 in 1998 to 1.78/100,000 in 2008. The prevalence of UC increased from 0.61/100,000 in 1998 to 7.62/100,000 in 2008. Male to female ratio for CD was 2.22 and 1.64 for UC. Age of registered for CD was predominantly between 20 to 39, and for UC between 30 to 49 years of age. The standardized mortality ratio (95% CI) was 4.97 (3.72-6.63) for CD and 1.78 (1.46-2.17) for UC, from 1998 to 2008 in Taiwan. CONCLUSIONS: Using the Taiwan nationwide database for IBD, the incidence and prevalence of IBD in Taiwan significantly increased from 1998 to 2008. The mortality rate was higher for CD patients than UC patients, and both were higher than the general population.


Assuntos
Colite Ulcerativa/epidemiologia , Doença de Crohn/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Colite Ulcerativa/mortalidade , Doença de Crohn/mortalidade , Feminino , Humanos , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Distribuição por Sexo , Taiwan/epidemiologia , Adulto Jovem
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