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1.
Cancers (Basel) ; 13(6)2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33809157

RESUMO

The study aimed to investigate the clinical significance of interim response evaluation during definitive chemoradiotherapy (dCRT) in predicting overall treatment response and survival of patients with locally advanced esophageal squamous cell carcinoma (LAESCC). We reviewed 194 consecutive patients treated with dCRT for biopsy-confirmed LAESCC. A total of 51 patients met the inclusion criteria. Interim response was assessed by defining a region of interest in initial and adaptive computed tomography (CT) images and subsequently examined against the overall treatment response assessed three months after dCRT, treatment failure pattern, overall survival (OS), and progression-free survival (PFS) estimates. Reductions in both the area and maximal diameter of the primary lesion (p < 0.001; p < 0.001, respectively) and those of the metastatic lymph nodes (LN) (p = 0.002; p < 0.001, respectively) in interim analysis were significantly higher among patients who achieved complete response (CR) than among those who did not. OS was significantly longer among patients who showed ≥30% interim reduction in the area and maximal diameter of the primary lesion and among those who showed such reduction in both the primary lesion and LN. PFS was significantly longer in the patients with ≥30% interim reduction in the area of the primary lesion. In addition, the proportion of cases with locoregional failure began decreasing at interim response of 20% or higher, while the proportion of cases with outfield failure followed the opposite pattern, increasing at interim response of 20% or higher. Among patients treated with dCRT for LAESCC, interim response assessed using adaptive CT images correlated with overall CR and OS rates. The evaluation of tumor burden reduction during dCRT may help predict patient prognosis.

2.
Nature ; 590(7847): 642-648, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33536616

RESUMO

Tissue damage increases the risk of cancer through poorly understood mechanisms1. In mouse models of pancreatic cancer, pancreatitis associated with tissue injury collaborates with activating mutations in the Kras oncogene to markedly accelerate the formation of early neoplastic lesions and, ultimately, adenocarcinoma2,3. Here, by integrating genomics, single-cell chromatin assays and spatiotemporally controlled functional perturbations in autochthonous mouse models, we show that the combination of Kras mutation and tissue damage promotes a unique chromatin state in the pancreatic epithelium that distinguishes neoplastic transformation from normal regeneration and is selected for throughout malignant evolution. This cancer-associated epigenetic state emerges within 48 hours of pancreatic injury, and involves an 'acinar-to-neoplasia' chromatin switch that contributes to the early dysregulation of genes that define human pancreatic cancer. Among the factors that are most rapidly activated after tissue damage in the pre-malignant pancreatic epithelium is the alarmin cytokine interleukin 33, which recapitulates the effects of injury in cooperating with mutant Kras to unleash the epigenetic remodelling program of early neoplasia and neoplastic transformation. Collectively, our study demonstrates how gene-environment interactions can rapidly produce gene-regulatory programs that dictate early neoplastic commitment, and provides a molecular framework for understanding the interplay between genetic and environmental cues in the initiation of cancer.


Assuntos
Transformação Celular Neoplásica/genética , Epigênese Genética , Interação Gene-Ambiente , Pâncreas/metabolismo , Pâncreas/patologia , Adenocarcinoma/genética , Adenocarcinoma/patologia , Animais , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Transformação Celular Neoplásica/patologia , Cromatina/genética , Cromatina/metabolismo , Cromatina/patologia , Modelos Animais de Doenças , Feminino , Genômica , Humanos , Interleucina-33/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
3.
PLoS One ; 16(2): e0245052, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33544706

RESUMO

Emerging evidence that an elevated serum gamma-glutamyltransferase (GGT) level is associated with an increased risk of gastrointestinal cancer, but still controversial. The aim of this study to assess the relationship between GGT level and risk of gastrointestinal cancer, and the contribution of the interaction of hyperglycemia with elevated GGT level to the incidence of gastrointestinal cancer by the stratified analysis. A total of 8,120,665 Koreans who received medical checkups in 2009 were included. Subjects were classified according to the quartile of GGT level for women and men. The incidence rates of gastrointestinal cancer for each group were analyzed using Cox proportional hazards models. During follow-up, 129,853 cases of gastrointestinal cancer newly occurred (esophagus, 3,792; stomach, 57,932; and colorectal, 68,789 cases). The highest GGT quartile group showed an increased risk of gastrointestinal cancer (esophagus, hazard ratio = 2.408 [95% confidence interval, 2.184-2.654]; stomach, 1.121 [1.093-1.149]; and colorectal, 1.185 [1.158-1.211]). The risk increased significantly with the rise in GGT quartile level, regardless of the site of cancer. The stratified analysis according to glycemic status showed that the effect of elevated GGT was predominant in the risk of esophageal cancer. The effect of elevated GGT further increased the risk of stomach and colorectal cancers in diabetic patients. An elevated level of GGT was associated with an increased risk of gastrointestinal cancer, regardless of the site of cancer. The effect of the increase in GGT level on the risk of gastrointestinal cancer depended on the type of cancer and glycemic status.

4.
J Crohns Colitis ; 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33175122

RESUMO

BACKGROUND & AIMS: Robust evidence regarding the impact of disease activity on pregnancy outcomes in women with IBD is crucial for both clinicians and patients in preparing a birth plan. We sought to perform a systematic review and meta-analysis to assess the pooled influences of disease activity on pregnancy outcomes in women with IBD. METHODS: We searched MEDLINE, EMBASE, and COCHRANE library to identify articles comparing pregnancy outcomes between active and inactive IBD at the time of conception or during pregnancy. A meta-analysis was performed using a random-effects model to pool estimates and report odds ratios (ORs). RESULTS: A total of 28 studies were identified as eligible for the meta-analysis. In women with active IBD, the pooled ORs for low birth weight (LBW), preterm birth, small for gestational age (SGA), spontaneous abortion, and stillbirths were 3.81 (95% confidence interval [CI] 1.81-8.02), 2.42 (95% CI 1.74-3.35), 1.48 (95% CI 1.19-1.85), 1.87 (95% CI 1.17-3.0), and 2.27 (95% CI 1.03-5.04) compared to women with inactive IBD, respectively. In the subgroup analysis based on disease type, women with active ulcerative colitis had an increased risk of LBW, preterm birth, and spontaneous abortion. Women with active Crohn's disease had a higher risk of preterm birth, SGA, and spontaneous abortion. CONCLUSIONS: Active IBD during the periconception period and pregnancy is associated with increased risk of adverse pregnancy outcomes. Our data suggest that pregnancy should be planned when the disease is quiescent, and continuous disease control is important even during pregnancy.

5.
World J Gastroenterol ; 26(37): 5661-5672, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33088159

RESUMO

BACKGROUND: Periodontitis is a chronic inflammation of periodontal tissues. The effect of periodontitis on the development of inflammatory bowel disease (IBD) remains unclear. AIM: To assessed the risk of IBD among patients with periodontitis, and the risk factors for IBD related to periodontitis. METHODS: A nationwide population-based cohort study was performed using claims data from the Korean National Healthcare Insurance Service. In total, 9950548 individuals aged ≥ 20 years who underwent national health screening in 2009 were included. Newly diagnosed IBD [Crohn's disease (CD), ulcerative colitis (UC)] using the International Classification of Disease 10th revision and rare intractable disease codes, was compared between the periodontitis and non-periodontitis groups until 2017. RESULTS: A total of 1092825 individuals (11.0%) had periodontitis. Periodontitis was significantly associated with older age, male gender, higher body mass index, quitting smoking, not drinking alcohol, and regular exercise. The mean age was 51.4 ± 12.9 years in the periodontitis group and 46.6 ± 14.2 years in the non-periodontitis group (P < 0.01), respectively. The mean body mass index was 23.9 ± 3.1 and 23.7 ± 3.2 in the periodontitis and non-periodontitis groups, respectively (P < 0.01). Men were 604307 (55.3%) and 4844383 (54.7%) in the periodontitis and non-periodontitis groups, respectively. The mean follow-up duration was 7.26 years. Individuals with periodontitis had a significantly higher risk of UC than those without periodontitis [adjusted hazard ratio: 1.091; 95% confidence interval (CI): 1.008-1.182], but not CD (adjusted hazard ratio: 0.879; 95% confidence interval: 0.731-1.057). The risks for UC were significant in the subgroups of age ≥ 65 years, male gender, alcohol drinker, current smoker, and reduced physical activity. Current smokers aged ≥ 65 years with periodontitis were at a 1.9-fold increased risk of UC than non-smokers aged ≥ 65 years without periodontitis. CONCLUSION: Periodontitis was significantly associated with the risk of developing UC, but not CD, particularly in current smokers aged ≥ 65 years.

6.
PLoS One ; 15(9): e0238244, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32898174

RESUMO

Anemia is a common manifestation of inflammatory bowel disease (IBD), but it remains unclear whether anemia is associated with the development of IBD. We assessed the risk of developing IBD in anemic patients, and stratified the results with respect to their hemoglobin concentrations. A population-based study was conducted using the National Healthcare Insurance Service database in South Korea. We included individuals over 20 years' old who participated in the national health screening program in 2009 (n = 9,962,064). Anemia was defined as a hemoglobin level less than 13 g/dL in men and less than 12 g/dL in women. We compared the rate of newly diagnosed IBD in anemic patients and non-anemic individuals. Newly diagnosed IBD was identified using both the ICD-10 medical code and specialized V codes for rare intractable diseases in South Korea. During the mean follow-up period of 7.3 years, the incidences of CD and UC in anemic patients were 2.89 and 6.88 per 100,000 person-years, respectively. The risk of CD was significantly higher in anemic patients than in non-anemic individuals [adjusted hazard ratio (aHR), 2.084; 95% confidence interval (CI), 1.769-2.455]. The risk of CD development was inversely proportional to the hemoglobin concentration. A J-curve relationship was observed between age and the risk of CD in anemic patients. The risk of CD in male anemic patients was significantly higher than that in female anemic patients (aHR, 1.432 vs. 1.240, respectively). By contrast, there was no statistically significant difference in the risk of developing UC in anemic and non-anemic individuals (aHR, 0.972; 95% CI, 0.880-1.073). This work indicates that anemia is related to the development of CD, and this risk was inversely proportional to the hemoglobin concentration.


Assuntos
Anemia/complicações , Colite Ulcerativa/etiologia , Doença de Crohn/etiologia , Estudos de Coortes , Colite Ulcerativa/epidemiologia , Doença de Crohn/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Fatores de Risco
7.
Artigo em Inglês | MEDLINE | ID: mdl-32712393

RESUMO

BACKGROUND & AIMS: The association between atopic diseases and inflammatory bowel diseases (IBD) is unclear. We conducted a nationwide population-based study in Korea to investigate the effect of atopic diseases on the development of IBD. METHODS: A total of 9,923,521 participants, who received a medical check-up in 2009, were included and followed through 2017. The presence of any atopic diseases, including atopic dermatitis (AD), allergic rhinitis (AR), and asthma, was evaluated. Patients who developed IBD, including Crohn's disease (CD) and ulcerative colitis (UC), were identified using claims data from National Health Insurance; the association between atopic diseases and the risk of IBD was evaluated using Cox proportional hazard models, and presented as adjusted hazard ratios (aHRs) with 95% CIs. RESULTS: During a mean follow-up period of 7.3 years, 1419 patients (0.014%) developed CD and 5897 patients (0.059%) developed UC. The incidences of CD (per 100,000 person-years) were 3.756, 2.248, and 2.346 in patients with AD, AR, or asthma, respectively. The incidences of UC were 11.952, 9.818, and 9.358 in patients with AD, AR, or asthma, respectively. Multivariable analysis revealed that the aHRs for incident CD in patients with AD, AR, or asthma were 2.02, 1.33, and 1.60 (95% CIs, 1.118-3.663, 1.149-1.529, and 1.193-2.136, respectively) compared with controls. The risks of incident UC in patients with AD, AR, or asthma were 1.51, 1.32, and 1.29 (95% CIs, 1.082-2.104, 1.229-1.410, and 1.115-1.491, respectively) compared with controls. Moreover, an increase in the number of atopic diseases gradually increased the risk for CD and UC; for 1 or 2 or more atopic diseases, the aHRs for CD were 1.35 and 1.65 (95% CIs, 1.171-1.560 and 1.146-2.376), and the aHRs for UC were 1.30 and 1.49 (95% CIs, 1.211-1.392 and 1.249-1.774), respectively. CONCLUSIONS: Based on a nationwide population-based study in Korea, patients with any atopic disease, including AD, AR, or asthma, have an increased risk for CD and UC. The risk for IBD increases with the increase in the number of atopic diseases.

8.
Intest Res ; 18(1): 18-33, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32013312

RESUMO

The treatment of inflammatory bowel disease (IBD) has been revolutionized for the last 10 years by the increasing use of immunomodulators and biologics. With immunosuppression of this kind, opportunistic infection is an important safety concern for patients with IBD. In particular, viral hepatitis is determined by the interaction between the virus and the host's immunity, and the risk of reactivation increases if immunity is compromised by immunosuppression therapy. Parts of Asia, including Korea, still show intermediate endemicity for the hepatitis A virus and hepatitis B virus compared with the United States and Western Europe. Thus, members of IBD research group of the Korean Association for the Study of Intestinal Diseases have produced a guideline on the prevention and management of viral hepatitis in IBD.

9.
Inflamm Bowel Dis ; 26(6): 852-862, 2020 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-31895948

RESUMO

BACKGROUND: Selective blocking of HDAC6 has become a promising strategy in treating inflammatory bowel disease. CKD-506 is a novel isoform-selective inhibitor of histone deacetylase 6. The present study was performed to evaluate the effect of CKD-506 on the NF-κB signaling pathway in intestinal epithelial cells (IECs) and macrophages and on murine models of acute and chronic colitis. METHODS: RAW264RAW264.7 murine macrophages and COLO 205 human IECs were pretreated with CKD-506 and then stimulated with lipopolysaccharides (LPS). Cytokine expression of TNF-α, interleukin (IL)-6, IL-8, and IL-10 was measured by ELISA. The effect of CKD-506 on NF-κB signaling was evaluated by Western blotting of IκBα phosphorylation/degradation and electrophoretic mobility shift assay. In vivo studies were performed using a dextran sulfate sodium (DSS)-induced acute colitis model, a chronic colitis model in IL-10 knockout mice, and an adoptive transfer model. Colitis was quantified by the disease activity index, colon length, and histopathologic evaluation. RESULTS: CKD-506 suppressed the expression of pro-inflammatory cytokines such as IL-6, IL-8, and TNF-α in IECs and macrophages. CKD-506 strongly inhibited IκBα phosphorylation/degradation and the DNA-binding activity of NF-κB. Oral administration of CKD-506 attenuated DSS-induced acute colitis and chronic colitis in IL-10-/- and adoptive transfer models. CKD-506 ameliorated weight loss, disease activity, and histopathologic score in colitis mice and downregulated IκBα phosphorylation and pro-inflammatory cytokine production significantly. CONCLUSIONS: CKD-506 blocked NF-κB signaling in IECs and macrophages and ameliorated experimental acute and chronic murine colitis models, which suggests that CKD-506 is a promising candidate for inflammatory bowel disease treatment as a small molecular medicine.

10.
Gut Liver ; 14(5): 589-600, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-31816671

RESUMO

Background/Aims: Ghrelin agonists are emerging prokinetic agents for treating gastroparesis. Although recent clinical trials have demonstrated their efficacy in patients with diabetic gastroparesis (DG), the impact of such agents on symptoms and gastric dysmotility remains unclear. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of ghrelin agonists in patients with DG. Methods: A search of common electronic databases (MEDLINE, Embase, and Cochrane Central Register of Controlled Trials) was preformed, using keyword combinations that referenced ghrelin and DG and retrieving all eligible randomized controlled trials (RCTs) of ghrelin agonists versus placebo in patients with DG. The primary outcome measure was the change in patient-reported overall gastroparesis symptom scores. Secondary outcomes included the change in gastric emptying time, specific symptoms related to gastroparesis, and adverse events. A random-effects model was applied to all study outcomes. Heterogeneity among studies was determined by the chi-square test and I2 statistics. Results: We selected six RCTs of patients with DG (n=557) for meta-analysis. Ghrelin agonist administration (vs placebo) significantly improved overall gastroparesis symptoms (standardized mean difference, -0.34; 95% confidence interval, -0.56 to -0.13) and significantly improved symptoms related to gastroparesis, including nausea, vomiting, early satiety, and abdominal pain. Adverse events recorded for ghrelin agonists and placebo did not differ significantly. There was no significant heterogeneity among eligible studies. Conclusions: Compared with placebo, ghrelin agonists are effective and well-tolerated for the treatment of DG.

11.
Gut Liver ; 14(6): 755-764, 2020 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-31816672

RESUMO

Background/Aims: The risk for colonoscopic postpolypectomy bleeding (PPB) in patients with chronic liver disease (CLD) remains unclear. We determined the incidence and risk factors for colonoscopic PPB in patients with CLD, especially those with liver cirrhosis. Methods: We retrospectively reviewed the medical records of patients with CLD who underwent colonoscopic polypectomy at Seoul National University Hospital between 2011 and 2014. The study endpoints were immediate and delayed PPB. Results: A total of 1,267 consecutive patients with CLD were included in the study. Immediate PPB occurred significantly more often in the Child- Pugh (CP) B or C cirrhosis group (17.5%) than in the CP-A (6.3%) and chronic hepatitis (4.6%) groups (p<0.001). Moreover, the incidence of delayed PPB in the CP-B or C cirrhosis group (4.4%) was significantly higher than that in the CP-A (0.7%) and chronic hepatitis (0.2%) groups (p<0.001). The independent risk factors for immediate PPB were CP-B or C cirrhosis (p=0.011), a platelet count <50,000/µL (p<0.001), 3 or more polyps (p=0.017), endoscopic mucosal resection or submucosal dissection (p<0.001), and polypectomy performed by trainees (p<0.001). The independent risk factors for delayed PPB were CP-B or C cirrhosis (p=0.009), and polyps >10 mm in size (p=0.010). Conclusions: Patients with CP-B or C cirrhosis had an increased risk for bleeding following colonoscopic polypectomy.

12.
Korean J Intern Med ; 35(4): 889-896, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31878772

RESUMO

BACKGROUND/AIMS: Capsule endoscopy (CE) is widely used for the diagnosis of small bowel diseases. The clinical performance and complications of small bowel CE, including completion rate, capsule retention rate, and indications, have been previously described in Korea. This study aimed at estimating the recent changes in clinical performance and complications of small bowel CE based on 17-year data from a Korean Capsule Endoscopy Registry. METHODS: CE registry data from 35 hospitals were retrospectively analyzed. Clinical information, including completion rate, capsule retention rate, and indications, was collected and analyzed. In addition, the most recent 5-year data for CE examinations were compared with the previous 12-year data. RESULTS: A total of 4,650 CE examinations were analyzed. The most common indication for CE was obscure gastrointestinal bleeding (OGIB). The overall incomplete examination rate was 16% and the capsule retention rate was 3%. Crohn's disease was a risk factor for capsule retention. Inadequate bowel preparation was significantly associated with capsule retention and incomplete examination. An indication other than OGIB was a risk factor for incomplete examination. A recent increasing trend of CE diagnosis of Crohn's disease was observed. The most recent 5-year incomplete examination rate for CE examinations decreased compared with that of the previous 12 years. CONCLUSION: The 17-year data suggested that CE is a useful and safe tool for diagnosing small bowel diseases. The incomplete examination rate of CE decreased with time, and OGIB was consistently the main indication for CE. Inadequate bowel preparation was significantly associated with capsule retention and incomplete examination.

13.
Surg Endosc ; 34(11): 5046-5054, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31820151

RESUMO

BACKGROUND AND STUDY AIMS: Biopsy-based histologic diagnosis is important in determining the treatment strategy for early gastric cancer (EGC). However, there are few studies on how histologic discrepancy may affect patients' treatment outcomes. We aimed to investigate the impact of histopathologic differences between biopsy and final specimens from endoscopic resection (ER) or gastrectomy on treatment outcomes in patients with EGC. We also examined the predictive factors of histologic discrepancy. PATIENTS AND METHODS: We analyzed the data of 1851 patients with EGC treated with ER or gastrectomy. We compared the histology between biopsies and final resected specimens from ER or gastrectomy. We also examined changes in treatment outcomes according to histologic differences. RESULTS: Histologic discrepancy was observed in 11.9% of patients in the ER group and 10.7% of those in the gastrectomy group. In patients treated with ER who showed histologic discrepancy, 80.9% showed differentiated-type EGC (D-EGC) on biopsy but undifferentiated-type-EGC (UD-EGC) after ER, of which 78.9% were non-curative resection. In patients treated with gastrectomy who showed histologic discrepancy, 39% showed UD-EGC on biopsy but showed D-EGC after gastrectomy. A total of these patients had absolute and expanded indications for ER. Moderately differentiated and poorly differentiated adenocarcinoma on biopsy were predictive factors of histologic discrepancy in UD-EGC and D-EGC on final resection, respectively. CONCLUSIONS: About 10% of patients showed histologic discrepancy between biopsy and final resection with ER or gastrectomy. Histologic discrepancy can affect treatment outcomes, such as non-curative resection in ER or missing the opportunity for ER in gastrectomy.

14.
Inflamm Bowel Dis ; 26(2): 242-253, 2020 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-31586441

RESUMO

BACKGROUND: Tumor necrosis factor (TNF)-α is a major proinflammatory cytokine that plays a key role in inflammatory bowel disease (IBD). Inactive rhomboid protein 2 (iRhom2) is essential for activating TNF-α-converting enzyme (TACE) in immune cells, which regulates TNF-α release. The aim of the study was to investigate the role of iRhom2 in intestinal inflammation in IBD. METHODS: The expression of iRhom2 and TACE in lipopolysaccharide (LPS)-stimulated COLO 205 and RAW 264.7 cells was assessed by reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis. The expression of iRhom2 and TACE in the colonic tissue of IBD patients and 2,4,6-trinitrobenzenesulfonic acid solution (TNBS)-treated mice was determined by RT-PCR and immunohistochemistry. To assess the role of iRhom2 in intestinal inflammation, colitis was induced in wild-type and iRhom2-/- mice by the administration of TNBS enema. RESULTS: In LPS-stimulated COLO 205 and RAW 264.7 cells, the mRNA and protein levels of TACE and iRhom2 were upregulated. The expression of TACE and iRhom2 in the colon of the IBD patients and TNBS-treated mice was significantly enhanced. The inflammatory cells that expressed high levels of iRhom2 in the colon were identified as macrophages. Finally, iRhom2 deficiency ameliorated TNBS-induced colitis by inhibiting TNF-α release. CONCLUSIONS: iRhom2 has an important role in intestinal inflammation through TNF-α secretion in immune cells, which suggests that iRhom2 could be a novel therapeutic target for IBD.


Assuntos
Proteínas de Transporte/fisiologia , Colite/etiologia , Inflamação/etiologia , Intestinos/imunologia , Macrófagos/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Animais , Colite/patologia , Citocinas , Inflamação/metabolismo , Inflamação/patologia , Intestinos/efeitos dos fármacos , Intestinos/patologia , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Estresse Oxidativo , Ácido Trinitrobenzenossulfônico/toxicidade
15.
J Gastroenterol Hepatol ; 35(2): 249-255, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31420894

RESUMO

BACKGROUND AND AIM: The relationship between inflammatory bowel disease (IBD) and idiopathic pulmonary fibrosis (IPF) remains unclear. We evaluated the risk for developing IPF in patients with IBD using a nationwide population-based study. METHODS: Using claims data from the National Health Insurance service in Korea, patients with IBD, including Crohn's disease (CD) and ulcerative colitis (UC), were identified through both the 10th revision of the International Statistical Classification of Diseases and Related Health Problems and rare and intractable disease program codes from January 2010 to December 2013. We compared 38 921 IBD patients with age-matched and sex-matched individuals without IBD in a ratio of 1:3. Patients with newly diagnosed IPF were identified by both the 10th revision of the International Statistical Classification of Diseases and Related Health Problems and rare and intractable disease registration codes. RESULTS: During a mean 4.9-year follow-up, the incidence of IPF in patients with IBD was 33.21 per 100 000 person-years. The overall risk of IPF was significantly higher in IBD patients than in non-IBD controls (hazard ratio [HR], 1.62; 95% confidence interval [CI], 1.20-2.20; P = 0.003). In patients with CD, the incidence (per 100 000 person-years) of IPF was 26.04; in controls, the incidence was 9.15 (HR, 2.89; 95% CI, 1.46-5.72; P = 0.002). The incidence of IPF in patients with UC tended to be higher than in controls (36.66 vs 26.54 per 100 000 person-years; 95% CI, 0.99-1.99; HR, 1.41; P = 0.066). The risk of developing IPF in patients with IBD was higher in male patients than in female patients (P = 0.093 in CD; P = 0.147 in UC by interaction analysis). CONCLUSIONS: Patients with IBD, especially CD, have an increased risk of developing IPF.


Assuntos
Doenças Inflamatórias Intestinais/epidemiologia , Adulto , Feminino , Seguimentos , Humanos , Fibrose Pulmonar Idiopática/epidemiologia , Fibrose Pulmonar Idiopática/etiologia , Doenças Inflamatórias Intestinais/complicações , Masculino , Pessoa de Meia-Idade , Prevalência , República da Coreia , Risco , Fatores de Tempo , Adulto Jovem
16.
J Gastroenterol Hepatol ; 35(1): 29-36, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31396995

RESUMO

BACKGROUND AND AIM: PBK-1701TC is a novel sulfate tablet-based that contains 320 mg of simethicone and delivers 90% of the salt and water delivered by oral sulfate solution (OSS) preparation. This study evaluated the efficacy, safety, and tolerability of PBK-1701TC compared with OSS in bowel preparation for colonoscopy. METHODS: This randomized, multicenter, phase 3 non-inferiority trial included adults aged 19 years or older with a body mass index of 19-30 kg/m2 undergoing colonoscopy at five university hospitals in Korea. The primary efficacy endpoint was successful bowel-cleansing rate, defined as Harefield Cleansing Scale grade A or B as evaluated by blinded central readers. Secondary endpoints included the presence of residual air bubbles. Adverse events and laboratory evaluations were monitored to assess safety. Tolerability was assessed via participant interview. RESULTS: Overall, 235 participants were randomized, and 224 were included in the per-protocol analysis (PBK, 112; OSS, 112). Successful bowel cleansing was achieved for 95.5% (107/112) in the PBK group, which was non-inferior to the OSS group (98.2%, 110/112) with a difference of -2.7% (one sided 97.5% confidence limit, -8.1%). The participants in the PBK group had fewer intraluminal bubbles (0.9% vs 81.3%, P < 0.001) and reported a lower incidence of nausea and vomiting, with better acceptance, taste, and willingness to repeat the regimen than those in the OSS group (all P < 0.05). CONCLUSION: The novel sulfate tablet, PBK-1701TC, was non-inferior to OSS with respect to bowel-cleansing efficacy and exhibited better safety and tolerability in adults undergoing colonoscopy.


Assuntos
Sulfatos/administração & dosagem , Administração Oral , Adulto , Idoso , Catárticos/administração & dosagem , Colonoscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Soluções , Comprimidos , Adulto Jovem
17.
Gut Liver ; 14(1): 89-99, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31158951

RESUMO

Background/Aims: We aimed to investigate the differences in direct healthcare costs between patients with and without inflammatory bowel disease (IBD) and changes in direct healthcare costs before and after IBD diagnosis. Methods: This population-based study identified 34,167 patients with IBD (11,014 patients with Crohn's disease and 23,153 patients with ulcerative colitis) and 102,501 age-and sex-matched subjects without IBD (the control group) from the National Health Insurance database using the International Classification of Disease, 10th revision codes and the rare intractable disease registration program codes. The mean healthcare costs per patient were analyzed for 3 years before and after IBD diagnosis, with follow-up data available until 2015. Results: Total direct healthcare costs increased and peaked at $2,396 during the first year after IBD diagnosis, but subsequently dropped sharply to $1,478 during the second year after diagnosis. Total healthcare costs were higher for the IBD patients than for the control group, even in the third year before the diagnosis ($497 vs $402, p<0.001). The costs for biologics for the treatment of IBD increased steeply over time, rising from $720.8 in the first year after diagnosis to $1,249.6 in the third year after diagnosis (p<0.001). Conclusions: IBD patients incurred the highest direct healthcare costs during the first year after diagnosis. IBD patients had higher costs than the control group even before diagnosis. The cost of biologics increased steeply over time, and it can be assumed that biologics could be the main driver of costs during the early period after IBD diagnosis.


Assuntos
Colite Ulcerativa/economia , Doença de Crohn/economia , Custos de Cuidados de Saúde/estatística & dados numéricos , Doenças Inflamatórias Intestinais/economia , Adolescente , Adulto , Estudos de Casos e Controles , Colite Ulcerativa/epidemiologia , Efeitos Psicossociais da Doença , Doença de Crohn/epidemiologia , Bases de Dados Factuais , Feminino , Humanos , Doenças Inflamatórias Intestinais/epidemiologia , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Estudos Retrospectivos , Adulto Jovem
18.
Clin Gastroenterol Hepatol ; 18(9): 2010-2018.e2, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31446180

RESUMO

BACKGROUND & AIMS: Thiopurine-related myelosuppression (most frequently leukopenia) interferes with thiopurine therapy for patients with inflammatory bowel diseases (IBD). We investigated whether pretreatment analyses genetic variants associated with thiopurine-induced leukopenia could be used to effectively identify patients who required dose adjustments. METHODS: We performed a multicenter, prospective study of patients with IBD at 5 tertiary medical centers in Korea, from January 2016 through September 2018. Seventy-two patients were randomly assigned to a group that underwent genotype analysis for the NUDT15 variant (rs116855232) and FTO variant (rs79206939) and 3 common TPMT variants (rs1800460, rs1800462, rs1142345) associated with myelosuppression and 92 patients were assigned to a group that did not undergo genotype analysis (non-genotyping group). Patients heterozygous for any variant received 50 mg azathioprine equivalents, whereas those who were homozygous for any variant received alternative drugs. Patients who did not carry any of the genetic variants and patients in the non-genotyping group received 50 mg azathioprine equivalents followed by dose escalation up to 2-2.5 mg/kg. Myelosuppression was defined as white blood cell counts below 3000/µL, levels of hemoglobin 10 g/dL, or platelet counts below 100 K/µL. RESULTS: Twelve patients (16.7%) in the genotype analysis group and 33 patients (35.9%) in the non-genotyping group developed myelosuppression (P=.005). A multivariate analysis revealed that body mass indices above 21 kg/m2 (hazard ratio [HR], 0.43; 95% CI, 0.22-0.81; P = .009), pretreatment genotype analysis (HR, 0.37; 95% CI, 0.18-0.77; P = .008), and the maximum dose of thiopurines (HR, 0.34; 95% CI, 0.19-0.59; P < .001) independently decreased risk of myelosuppression. Pretreatment genotype analysis reduced numbers of outpatient clinic visit and numbers of patients with drug discontinuation or dose reductions. CONCLUSIONS: In a randomized controlled study of patients undergoing thiopurine therapy for IBD, we found that selection of therapy based on genetic variants associated with thiopurine-induced leukopenia significantly reduced the proportion of patients with myelosuppression during treatment. ClinicalTrials.gov no: NCT03719118.

19.
Aliment Pharmacol Ther ; 51(4): 446-456, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31691306

RESUMO

BACKGROUND: The relationships between lipid profiles and IBD remain elusive. AIM: To determine the association of IBD with serum lipid profiles. METHODS: A nationwide population-based study was performed using claims data from the Korean National Healthcare Insurance service. A total of 9 706 026 subjects undergoing medical check-ups in 2009 were enrolled and followed up until 2016. Individuals who developed Crohn's disease (CD) or ulcerative colitis (UC) were identified during follow-up. Adjusted hazard ratio (aHR) by age, sex, body mass index, cigarette smoking, alcohol drinking, exercise, income and underlying comorbidities was calculated to define the impact of serum lipid profiles on developing IBD. RESULTS: During a median follow-up of 7.3 years, IBD was detected in 7,058 (0.07%) individuals. Compared with the highest quartile of serum total cholesterol (TC) levels, lower TC levels were associated with higher incidence of CD (aHR: Q1, 2.52; Q2, 1.52; Q3, 1.27), but not UC. Lower serum LDL-C levels were associated with higher incidence of CD (aHR: Q1, 1.92; Q2, 1.47; Q3, 1.22), but not UC. Moreover, lower serum HDL-C levels were associated with higher incidence of CD (aHR: Q1, 2.49; Q2, 1.90; Q3, 1.43), but not UC. In contrast, lower serum triglyceride levels were associated with higher incidence of UC (aHR: Q1, 1.22; Q2, 1.19; Q3, 1.19), but not CD. CONCLUSIONS: Low serum TC, LDL-C and HDL-C levels were associated with CD. Low serum triglyceride levels were related to UC.


Assuntos
Colite Ulcerativa/epidemiologia , Doença de Crohn/epidemiologia , Transtornos do Metabolismo dos Lipídeos/epidemiologia , Lipídeos/sangue , Adulto , Colite Ulcerativa/sangue , Comorbidade , Doença de Crohn/sangue , Feminino , Seguimentos , Humanos , Incidência , Transtornos do Metabolismo dos Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia
20.
PLoS One ; 14(12): e0226427, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31851694

RESUMO

BACKGROUND: Gastric cancer (GC) is categorized as diffuse- and intestinal-type adenocarcinoma. Intestinal-type GC is associated with chronic gastritis, atrophic gastritis (AG), and intestinal metaplasia (IM), precursors of dysplastic changes. Diffuse-type GC is generally known to undergo de novo carcinogenesis and is not associated with chronic mucosal changes. However, clinically, AG and IM are frequently observed surrounding diffuse-type GC. This study aimed to evaluate the role of AG and IM in diffuse-type GC. METHODS: We retrospectively reviewed the data of patients undergoing surgery for early GC. We divided patients with diffuse-type GC into two groups according to the presence of AG and IM based on Kyoto classification of gastritis. The clinicopathological characteristics were compared between the groups. RESULTS: Among patients with diffuse-type GC, 52.5% patients had AG and 18.4% had severe AG. With regard to IM, 42.1% patients had IM and 17.1% had severe IM. Diffuse-type GC combined with severe AG or IM showed larger tumor size and higher submucosal invasion rate than that without severe AG or IM. However, the lymph node metastasis (LNM) rate was not significantly different between the two groups. In multivariate analysis, severe AG or IM was not an independent risk factor for LNM. CONCLUSIONS: Severe AG or IM surrounding diffuse-type gastric cancer suggests a collapse of normal mucosal barriers and leads to the spread of cancer cells. Although the association between chronic mucosal changes and LNM is unclear, more caution is needed during endoscopy especially for complete resection of diffuse-type GC with these features.


Assuntos
Carcinogênese , Gastrite Atrófica/complicações , Neoplasias Gástricas/complicações , Idoso , Doença Crônica , Feminino , Gastrite Atrófica/patologia , Humanos , Masculino , Metaplasia/complicações , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia
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