关键词： Colitis-associated colorectal cancer   Dysplasia   Inflammation   Inflammatory bowel disease   Tumorigenesis  

摘要： The risk of colorectal cancer (CRC) is higher in patients with inflammatory bowel disease (IBD). Population-based data from patients with ulcerative colitis (UC) estimate that the risk of CRC is approximately 2- to 3-fold that of the general population;patients with Crohn's disease appear to have a similar increased risk. However, the true extent of colitis-associated cancer (CAC) in undertreated IBD is unclear. Data suggest that the size (i.e., severity and extent) and persistence of the inflammatory process is largely responsible for the development of CRC in IBD. As patients with IBD and CRC have a worse prognosis than those without a history of IBD, the impact of current therapies for IBD on CAC is of importance. Chronic inflammation of the gut has been shown to increase the risk of developing CAC in both UC and CD. Therefore, control of inflammation is pivotal to the prevention of CAC. This review presents an overview of the current knowledge of CAC in IBD patients, focusing on the role of inflammation in the pathogenesis of CAC and the potential for IBD drugs to interfere with the process of carcinogenesis by reducing the inflammatory process or by modulating pathways directly involved in carcinogenesis. (c) 2021 Published by Elsevier Ltd on behalf of Editrice Gastroenterologica Italiana S.r.l.

关键词： Calprotectin   Pregnancy   IBD   Cesarean section   Outcomes   Birth weight  

摘要： Background The role of fecal calprotectin in predicting pregnancy-related outcomes in inflammatory bowel disease (IBD) remains unknown. Aim To determine whether increased fecal calprotectin during pregnancy is associated with adverse pregnancy outcomes in IBD. Methods This is a multicenter cohort study of women with IBD who underwent fecal calprotectin monitoring during pregnancy. Fecal calprotectin levels were stratified by trimester, and adverse pregnancy-related outcomes were recorded. The Mann-Whitney U test assessed differences between continuous variables, whereas categorical variables were compared using the Chi-squared test. Results Eighty-five women with IBD were included. First trimester fecal calprotectin was higher in patients who underwent emergency Cesarean birth compared to those who had a vaginal delivery (503 ug/g, IQR 1554.3 ug/g vs. 130 ug/g, IQR 482 ug/g,p = .030, respectively) and in those who delivered infants with low birth weight compared to normal birth weight (1511 ug/g, IQR 579 ug/g vs. 168 ug/g, IQR 413 ug/g,p = .049, respectively). Third trimester fecal calprotectin was higher in those with non-elective induction of labor (334.5 ug/g, IQR 1411.0 ug/g) compared to those with spontaneous delivery (116.5 ug/g, IQR 227.1 ug/g) (p = .025). Those with a fecal calprotectin >= 250 ug/g in the second trimester had an increased incidence of infants with low birth weight (35.3% vs. 3.8%) (p = .049), whereas those with a fecal calprotectin >= 250 ug/g in the third trimester had an increased incidence of non-elective induction of labor (43.8% vs. 10.3%,p = .030). Conclusions Fecal calprotectin may be a useful noninvasive marker to predict adverse pregnancy-related outcomes in patients with IBD.

关键词： Inflammatory bowel disease   Psychiatric comorbidities   Transcriptome-wide association study   Linear modeling   Gene set networks  

摘要： Background: Inflammatory bowel disease (IBD) affects millions of people in North America, and patients with IBD have a high incidence of psychiatric comorbidities (PC). The genetic mechanisms underlying the link are, in general, poorly understood. Materials and methods: A transcriptome-wide association study (TWAS) was performed using genetically regulated gene expression profiles imputed from the genetic profiles of 240 IBD patients in the Manitoba IBD Cohort Study. The imputation was performed using the 44 non-diseased human tissue-specific reference models from the GTEx database. Linear modeling and gene set enrichment analysis were performed to identify genes and pathways that are significantly associated with IBD patients with PC compared to IBD alone in each of the 44 nondiseased human tissues. Finally, an enrichment map was generated to investigate networks of the enriched gene sets associated with IBD patients with PC. Results: The genes RBPMS in skeletal muscle (adjusted p = 0.05), KCNA5 in the cerebellar hemisphere of the brain (adjusted p = 0.09), GSR, SMIM34A, and LIPT2 in the frontal cortex of the brain (adjusted p = 0.09 for each) were the top genetically regulated genes with a suggestive association with IBD patients with PC. We identified three gene set networks, which include gene sets and pathways with a suggestive association with IBD patients with PC: one with 7 gene sets overlapping in apolipoprotein B mRNA editing subunit genes, one with 3 gene sets including pigmentation gene sets, and the other one with 3 gene sets including peptidyl tyrosine phosphorylation regulation related gene sets. Conclusions: Our TWAS analysis has identified genes and pathways with a suggestive association with IBD patients with PC. These findings can be potentially used for illustrating the mechanism of developing PC in the patients with IBD and developing diagnosis tool or drug targets for IBD patients with PC.

关键词： aneuploidy   colorectal cancer   DNA flow cytometry   dysplasia   inflammatory bowel disease  

摘要： Aims Several different non-conventional morphological patterns of epithelial dysplasia have been recently described in inflammatory bowel disease (IBD), but there is limited information regarding their clinicopathological and molecular features, as well as potential risk for high-grade dysplasia (HGD) or colorectal cancer (CRC) compared with conventional dysplasia developing in IBD. Methods and results A total of 317 dysplastic lesions from 168 IBD patients were analysed. All lesions were re-reviewed and subtyped as either conventional [including tubular adenoma-like (n = 183) and tubulovillous/villous adenoma-like (n = 56)] or non-conventional dysplasia [including dysplasia with increased Paneth cell differentiation (DPD, n = 40), crypt cell dysplasia (CCD, n = 14), goblet cell deficient (GCD, n = 10), hypermucinous (n = 7), sessile serrated lesion (SSL)-like (n = 4) and traditional serrated adenoma (TSA)-like (n = 3)]. DNA flow cytometry was performed on 70 low-grade conventional (n = 24) and non-conventional (n = 46) dysplastic biopsies to determine their malignant potential and molecular pathways to HGD or CRC. Eleven sporadic tubular adenomas with low-grade dysplasia (LGD) were utilised as controls. Seventy-eight non-conventional dysplastic lesions were identified in 56 (33%) of the 168 patients, whereas 239 conventional dysplastic lesions were identified in 149 (89%) patients. Although both non-conventional and conventional dysplasias were most often graded as LGD at diagnosis (83% and 84%, respectively), non-conventional dysplasia (38%) was more likely to develop HGD or CRC in the same colonic segment than conventional dysplasia (19%) on follow-up (P < 0.001). Almost half (46%) of non-conventional dysplastic samples showed aneuploidy, whereas only 8% of conventional dysplasia (P = 0.002) and 9% of sporadic tubular adenomas (P = 0.037) did. Also, non-conventional dysplasia more frequently presented as a flat/invisible lesion (41%) compared with conventional dy

摘要： Background and aims Children with inflammatory bowel disease (IBD) generally show an alteration in their fat and soft tissue mass contents. These alterations may influence disease severity and increase the risk of post-operative complications. Methods This is a retrospective cross-sectional study of patients with IBD, diagnosed and followed up between 2013 and 2018, in Jeddah, Saudi Arabia, who had dual-energy x-ray absorptiometry (DXA) scans for bone density evaluation. Obesity was defined based on fat mass index (FMI) and myopenia based on appendicular skeletal muscle mass (SMMa). Results This study incorporated 95 child and adolescent patients (52% female) with IBD: 59 with Crohn's disease (CD) and 36 with ulcerative colitis (UC), mean age 11.8 +/- 3.3 years and mean duration of illness 1.8 +/- 1.9 years. The most common disease phenotype and behaviour for CD patients were ileocolonic (57.6%) and non-stricturing and non-penetrating (76.3%). Of UC patients, 75% had extensive disease (pancolitis). Body composition profile in the total IBD cohort was classified as normal in 49.5%, obese in 26.3%, myopenic in 23.2% and myopenic-obese in 1.1%. The use of biological therapy was identified as a negative predictor for both obesity (OR = 7.0, 95% CI: 1.3-37.9, P = .02) and myopenia (OR = 0.11, 95% CI:0.02-0.47, P = .003), and female gender was shown to predict myopenia (OR = 3.5, 95% CI: 1.0-11.8, P = .04). Conclusions Saudi Arabian children with IBD showed comparable body composition profiles to adult patients with IBD. Biological therapy was associated with a decreased incidence of both obesity and myopenia, and female gender was found to predict myopenia.

摘要： Background Management of inflammatory bowel disease (IBD) has changed considerably over recent years, which has coincided with increased subspecialisation amongst general surgeons. This study evaluated the demographics and outcomes of patients with IBD undergoing bowel resection and assessed for the potential impact of surgical subspecialisation. Methods Patient demographic, operative and outcome data were collected for patients undergoing a bowel resection secondary to IBD, admitted acutely to NHS trusts in the North of England between 2002 and 2016. The primary outcome of interest was 30-day post-operative mortality, with secondary outcomes: length of stay, stoma and anastomosis rates. Results A total of 913 patients were included in the study cohort. A reduction in the number of resections was noted over time (2002-2006: 361 vs. 2012-2016: 262). No change was observed for 30-day mortality over the study period (3.9%, p = 0.233). Length of stay was also unchanged (p = 0.949). Laparoscopic surgery was increasingly utilised (0.6% vs. 17.2%, p < 0.001) in recent years, and by colorectal subspecialists (p = 0.003). More patients were managed by a colorectal consultant latterly (2002-2006: 45.4% vs. 2012-2016: 63.7%, p < 0.001). There was no difference between colorectal and other subspecialists in mortality (p = 0.156), length of stay (p = 0.201), stoma (p = 0.629) or anastomosis (p = 0.659) rates, including following multivariable adjustment. Conclusion The study demonstrated a significant reduction in the number of resections over time, increased utilisation of a laparoscopic approach and a shift towards the care of IBD surgical patients being by a colorectal subspecialist. However, these changes do not correspond with improved surgical outcomes.

关键词： Inflammatory bowel disease   Screening   Diagnosis   Colonoscopy   Colorectal cancer  

摘要： Background: Inflammatory bowel disease (IBD) is usually diagnosed in subjects with gastrointestinal symptoms, but may also be asymptomatic and diagnosed incidentally. Aims: to determine the prevalence of IBD in asymptomatic adults. Methods: we identified subjects who underwent colonoscopy between 1 September 2013 and 31 August 2019 in a regional colorectal cancer screening program with endoscopic findings suggestive of IBD, and retrieved their clinical, histological and therapeutic information. Results: 5116 subjects underwent colonoscopy, and 4640 persons were considered assessable. Of these, 54 (1.16%) had endoscopic findings suggestive of IBD, including 40 of Crohn?s disease (CD) and 14 of ulcerative colitis (UC). A definite diagnosis of IBD was made in 19 patients, for an overall IBD prevalence of 0.41%, with 13 cases of CD (0.28%) and 6 of UC (0.13%). The mean follow-up was 26.8 months after the first colonoscopy. Therapy was started in 5 of 13 CD patients and all UC patients. Conclusion: Endoscopic findings suggestive of IBD are not infrequent in an asymptomatic colorectal cancer screening population. Visualization of the terminal ileum is recommended in this setting. A definite diagnosis of IBD was made in about 1 out of 3 subjects with endoscopic lesions. Most IBD patients had a mild form of disease, but some needed biologic therapy. ? 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

关键词： 中药熏洗   针刺治疗   肛肠疾病   术后疗效  

摘要： 探讨肛肠疾病术后疼痛实施中药熏洗配合针刺治疗的临床效果。方法:遴选时段2019年4月-2020年4月内90例肛肠疾病手术患者,根据治疗方式差异分组,术后予以中药熏洗45例(对照组),实施中药熏洗+针刺治疗45例(研究组),对临床总疗效、症状改善情况、术后疼痛及水肿改善情况等指标对比分析。结果:研究组较对照组临床总有效率更高(93.33%vs73.33%)P<0.05;同时研究组治疗1d、7d、14d的VAS评分明显更低,且研究组(水肿、渗出物、疼痛等)临床症状改善时间以及创面愈合时间均更短,均较之对照组(P<0.05);研究组术后水肿改善情况较对照组更优(P<0.05)。结论:实施中药熏洗+针刺治疗对肛肠疾病术后疼痛具有明显镇痛效果,促进术后创面早期愈合及修复,改善水肿情况,进一步提高患者生活质量,改善预后。

关键词： Inflammatory bowel disease (IBD)   Ulcerative colitis (UC)   Crohn's disease (CD)   6-MITC   GSK-3 beta inhibitor   NF-kappa B regulation  

摘要： Inflammatory bowel disease (IBD) describes a set of disorders involving alterations to gastrointestinal physiology and mucosal immunity. Unravelling its complex pathophysiology is important since many IBD patients are refractory to or suffer adverse side effects from current treatments. Isothiocyanates (ITCs), such as 6-(methylsulfinyl)hexyl ITC (6-MITC) in Wasabia japonica, have potential anti-inflammatory activity. We aimed to elucidate the pathways through which 6-MITC alleviates inflammation by examining its role in the nuclear factor-kappa B (NF-kappa B) pathway through inhibition of glycogen synthase kinase 3 beta (GSK-3 beta) using a chemically induced murine model of IBD, cell-based and in silico techniques. The effects of 6-MITC and two NF-kappa B inhibitors, sulfasalazine (SS), pyrrolidine dithiolcarbamate (PDTC) were investigated on a dextran sulfate sodium (DSS)-induced murine mouse model of acute and chronic colitis using macroscopic measurements and pro-inflammatory markers. The effect of 6-MITC on NF-kappa B induction was assessed using a murine macrophage cell line. Complexes of GSK-3 beta-6-MITC and GSK-3 beta-ATP were generated in silico to elucidate the mechanism of 6-MITC's direct inhibition of GSK-3 beta. Changes in pro-inflammatory markers, inducible nitric oxide synthase (iNOS) (increased) and interleukin-6 (IL-6) (decreased) demonstrated that iNOS regulation occurred at the translational level. Intraperitoneal (ip) injection of 6-MITC to the colitis-induced mice ameliorated weight loss whereas oral administration had negligible effect. Fecal blood and colon weight/length ratio parameters improved on treatment with 6-MITC and the other NF-kappa B inhibitors. Levels of NF-kappa B decreased upon addition of 6-MITC in vitro while structural studies showed 6-MITC acts competitively to inhibit GSK-3 beta at the ATP binding site. In this study we demonstrated that 6-MITC inhibits NF-kappa B signaling via GSK-3 beta inhibition ameliorating fecal bloo