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A considerable number of patients with inflammatory bowel disease (IBD) experience extraintestinal manifestations (EIMs), which can present either before or after IBD diagnosis. Unraveling the pathogenic pathways of EIMs in IBD is challenging because of the lack of reliable criteria for diagnosis and difficulty in distinguishing EIMs from external pathologies caused by drugs or other etiologies. Optimizing treatment can also be difficult. Early diagnosis and management of EIM revolve around multidisciplinary teams, and they should have the resources necessary to make and implement appropriate decisions. In addition, specialists of the affected organs should be trained in IBD treatment. Furthermore, patient awareness regarding the extraintestinal symptoms of IBD is of paramount importance for improving patient understanding of disease and health outcomes. Herein, we review the pathogenesis and clinical perspectives of EIMs in IBD.
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Background/Aims Safety for tumor necrosis factor inhibitors (TNFi) in cancer has been focused on risk of incident malignancies, but studies on prognostic effects have been scarce. We determined survival and recurrence rates at 1, 2, and 5 years after cancer diagnosis in patients with and without concurrent TNFi use.
Methods Chart reviews were performed between 1996 and 2015 at the VA North Texas Healthcare System. Cases were patients with inflammatory disease, concomitant malignancy, and TNFi use while controls were patients with inflammatory disease, concomitant malignancy but no TNFi use. Cases and controls were matched for type of malignancy. Analysis was performed with log-rank tests on Kaplan-Meier curves.
Results Thirty-six cases and 72 controls were identified. For cases, survival at 1, 2, and 5 years were 32 (89%), 31 (86%), and 29 (81%) compared to 63 (90%), 61 (87%), and 51 (73%) for the control group (P=0.985). For cases, recurrence rates at 1, 2, and 5 years were 3 (8%), 5 (14%), and 6 (17%) compared to 2 (3%), 5 (7%), and 7 (10%) for the control group (P=0.158).
Conclusions Our findings suggest TNFi may be safely used in select inflammatory disease patients with concurrent cancer if therapy is needed for proper disease control. However, case-by-case consideration in conjunction with an oncologist is recommended while considering the apparent safety of TNFi for patients suffering from active inflammatory diseases despite having a concomitant malignancy.
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Background/Aims Inflammatory bowel disease (IBD) involves chronic inflammation of the colon with ulcerative colitis (UC), and the colon and/or small intestine with Crohn’s disease (CD). Pneumatosis intestinalis (PI), characterized by compromise of the intestinal wall with gas-filled cysts, has rarely been reported with IBD. The presentation, best management and outcomes of PI with IBD are poorly defined.
Methods We conducted a search for PI in all abdominal computed tomography (CT) reports at 2 large tertiary care hospitals from January 1, 2010 to December 31, 2017, cross referenced to ICD codes for IBD. CT and chart review was performed to confirm PI and IBD respectively. A systematic review excluding case reports was performed for PI with IBD for comparison.
Results Of 5,990 patients with a CT abdomen report mentioning PI, we identified 11 cases of PI with IBD, 4 UC, 6 CD, and 1 indeterminate colitis. PI was limited to the small bowel in 5 patients, the right colon in 5, and small bowel and colonic in 1. All 3 mortalities had CD, small intestinal PI and portal/mesenteric venous gas. The systematic literature search identified 9 articles describing 58 patients with IBD and PI. These cases were mostly included in larger cohorts of PI patients without extractable data on presentation or outcomes in the IBD subpopulation.
Conclusions Ours appears to be the first reporting of presentations and outcomes, outside of case reports, for those with PI and IBD. The high mortality for those with CD and PI of the small bowel appears to define a group requiring more than supportive medical care.
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Background/Aims Overwhelming evidence suggests that inflammatory bowel disease (IBD) is caused by a complicated interplay between the multiple genes and abnormal epigenetic regulation in response to environmental factors. It is becoming apparent that epigenetic factors are significantly associated with the development of the disease. DNA methylation remains the most studied epigenetic modification, and hypermethylation of gene promoters is associated with gene silencing.
Methods DNA methylation alterations may contribute to the many complex diseases development by regulating the interplay between external and internal environmental factors and gene transcriptional expression. In this study, we used 15 tumor suppressor genes (TSGs), originally identified in colon cancer, to detect promoter methylation in patients with Crohn’s disease (CD). Methylation specific polymerase chain reaction and bisulfite sequencing analyses were performed to assess methylation level of TSGs in CD patients.
Results We found 6 TSGs (sFRP1, sFRP2, sFRP5, TFPI2, Sox17, and GATA4) are robustly hypermethylated in CD patient samples. Bisulfite sequencing analysis confirmed the methylation levels of the sFRP1, sFRP2, sFRP5, TFPI2, Sox17, and GATA4 promoters in the representative CD patient samples.
Conclusions In this study, the promoter hypermethylation of the TSGs observed indicates that CD exhibits specific DNA methylation signatures with potential clinical applications for the noninvasive diagnosis of IBD and the prognosis for patients with IBD.
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SFRP5 inhibits melanin synthesis of melanocytes in vitiligo by suppressing the Wnt/β-catenin signaling Dao-Pei Zou, Yang-Mei Chen, Ling-Zhao Zhang, Xiao-Hui Yuan, Yu-Jie Zhang, Adelina Inggawati, Pham Thi Kieu Nguyet, Tian-Wen Gao, Jin Chen Genes & Diseases.2021; 8(5): 677. CrossRef
Background/Aims Latent tuberculosis screening is mandatory prior to initiating anti-tumor necrosis factor (anti-TNF) medications. Guidelines recommend interferon-gamma release assays (IGRA) as first line screening method for the general population. Studies provided conflicting evidence on IGRA and tuberculin skin test (TST) performance in inflammatory bowel disease (IBD) patients. We assessed test concordance and the effects of immunosuppression on their performance in IBD patients.
Methods We searched MEDLINE, Embase and Cochrane databases (2011–2018) for studies testing TST and IGRA in IBD. Primary outcome was TST and IGRA concordance. Secondary outcomes were effects of immunosuppressive therapy on performance. Immunosuppression defined as either steroids, thiopurine, methotrexate or cyclosporine use. We used the pooled random effects model to adjust for heterogeneity analyzed using (I2–Q statistics). We compared the fixed model to exclude smaller study effects.
Results Sixteen studies (2,488 patients) were included. Pooled TST and IGRA concordance was 85% (95% confidence interval [CI], 81%–88%; P=0.01). Effects of immunosuppression were reported in 8 studies (814 patients). The odds ratio of testing positive by IGRA decreased to 0.57 if immunosuppressed (95% CI, 0.31–1.03; P=0.06). The odds ratio of testing positive by TST if immunosuppressed was 1.14 (95% CI, 0.61–2.12; P=0.69). The fixed model yielded similar results, however the negative effect of immunosuppression on IGRA reached statistical significance (P=0.01).
Conclusions While concordance was 85% between TST and IGRA, the performance of IGRA seems to be negatively affected by immunosuppression. Given the importance of detecting latent tuberculosis prior to anti-TNF initiation, further randomized controlled trials comparing the performance of TST and IGRA in IBD patients are needed.
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Carlos Quezada-Gutiérrez, María Teresa Álvarez-Bañuelos, Jaime Morales-Romero, Clara Luz Sampieri, Raúl Enrique Guzmán-García, Evangelina Montes-Villaseñor
Intest Res 2020;18(3):315-324. Published online May 19, 2020
Background/Aims Colorectal cancer (CRC) is a public health problem. In Mexico, there have been no recent studies conducted on survival in terms of this pathology or on the influence of prognostic factors. The study aims to determine the probability of survival in patients with CRC presence of low levels of schooling and a rural population, adjusted for clinical stage and type of treatment.
Methods A retrospective study was conducted in a cohort of 305 patients with CRC treated at State Cancer Center, located in Veracruz-Mexico; the follow-up period of 60 months (2012–2016). The survival probability was calculated using the Kaplan-Meier estimator and the log-rank test with 95% confidence intervals (CIs). Prognostic factors were determined using hazard ratio (HR) multivariate Cox regression analysis.
Results Overall survival was 40% at 60 months. Subjects in the age group ≥ 65 years had a low survival rate of 28% (P= 0.026) and an advanced clinical stage of 22% (P< 0.001). Of the patients with bone metastasis, none survived longer than 5 years (P= 0.008). With respect to the unfavorable prognostic factors identified in the multivariate analysis, a decreased level of schooling was associated with an HR of 7.6 (95% CI, 1.1–54.7), advanced clinical stage was associated with an HR of 2.1 (95% CI, 1.2–4.0), and the presence of metastasis had an HR of 1.8 (95% CI, 1.1–2.9).
Conclusions Poor prognostic factors include an advanced clinical stage, the presence of metastasis and a low level of schooling. These findings confirm the importance of screening for early diagnosis, diminishing the barriers to accessing treatment and prospectively monitoring the population.
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Background/Aims Stress is closely related to the deterioration of digestive disease. Melatonin has potent anti-inflammatory properties. The objective of this study was to determine the effect of water stress (WS) and sleep deprivation (SD) on intestinal microbiota and roles of melatonin in stressful condition.
Methods We used C57BL/6 mice and specially designed water bath for stress and SD for 10 days. We measured melatonin concentrations in serum, feces, and colon tissues by high-performance liquid chromatography. Genomic DNA was extracted from feces and amplified using primers targeting V3 to V4 regions of bacterial 16S ribosomal RNA genes.
Results Compared to the control, melatonin concentration was lower in the WS and SD. Fecal concentration was 0.132 pg/mL in control, 0.062 pg/mL in WS, and 0.068 pg/mL in SD. In colon tissue, it was 0.45 pg/mL in control, 0.007 pg/mL in WS, and 0.03 pg/mL in SD. After melatonin treatment, melatonin concentrations in feces and colon tissue were recovered to the level of control. Metagenomic analysis of microbiota showed abundance in colitogenic microbiota in WS and SD. Melatonin injection attenuated this harmful effect. WS and SD showed decreased Lactobacillales and increased Erysipelotrichales and Enterobacteriales. Melatonin treatment increased Akkermansia muciniphila and Lactobacillus and decreased Bacteroides massiliensis and Erysipelotrichaceae.
Conclusions This study showed that stress and SD could affect intestinal dysbiosis and increase colitogenic microbiota, which could contribute to the aggravating digestive disease. Melatonin concentrations in feces and colon tissue decreased under WS and SD. Melatonin treatment brought recovery of melatonin concentration in colon tissue and modulating dysbiosis of intestinal microbiota.
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Gut dysbiosis can result in several diseases, including infections (Clostridium difficile infection and infectious gastroenteritis), autoimmune diseases (inflammatory bowel disease, diabetes, and allergic disorders), behavioral disorders and other conditions like metabolic syndrome and functional gastrointestinal disorders. Amongst various therapies targeting gut microbiome, fecal microbiota transplantation (FMT) is becoming a focus in the public media and peer reviewed literature. We have been using FMT for induction of remission in patients with moderate to severe active ulcerative colitis (UC) and also for subsequent maintenance of remission. Four cases reported incidental benefits while being treated with FMT for UC. These included weight loss (n=1), improvement in hair loss (n=1), amelioration of axial arthritis (n=1) and improvement in allergic rhinitis (n=1), thereby suggesting potential clinical applications of FMT in treating extraintestinal diseases associated with gut dysbiosis.
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