Colorectal cancer surveillance in inflammatory bowel disease： The search continues

Patients with inflammatory bowel disease （IBD） are at increased risk for colorectal cancer （CRC）. Risk factors for the development of CRC in the setting of IBD include disease duration, anatomic extent of disease, age at time of diagnosis, severity of inflammation, family history of colon cancer, and concomitant primary sclerosing cholangitis. The current surveillance strategy of surveillance colonoscopy with multiple random biopsies most likely reduces morbidity and mortality associated with IBD-related CRC. Unfortunately, surveillance colonoscopy also has severe limitations including high cost, sampling error at time of biopsy, and interobserver disagreement in histologically grading dysplasia. Furthermore, once dysplasia is detected there is disagreement about its management. Advances in endoscopic imaging techniques are already underway, and may potentially aid in dysplasia detection and improve overall surveillance outcomes. Management of dysplasia depends predominantly on the degree and focality of dysplasia, with the mainstay of management involving either proctocolectomy or continued colonoscopic surveillance. Lastly, continued research into additional chemopreventive agents may increase our arsenal in attempting to reduce the incidence of IBD-associated CRC.     

Gut microbiota,inflammatory bowel disease and colorectal cancer

The gut microbiota is a complex community of microorganisms that inhabit the digestive tracts of humans, living in symbiosis with the host. Dysbiosis, characterized by an imbalance between the beneficial and opportunistic gut microbiota, is associated with several gastrointestinal disorders, such as irritable bowel syndrome (IBS); inflammatory bowel disease (IBD), represented by ulcerative colitis and Crohn’s disease; and colorectal cancer (CRC). Dysbiosis can disrupt the mucosal barrier, resulting in perpetuation of inflammation and carcinogenesis. The increase in some specific groups of harmful bacteria, such as Escherichia coli (E. coli) and enterotoxigenic Bacteroides fragilis (ETBF), has been associated with chronic tissue inflammation and the release of pro-inflammatory and carcinogenic mediators, increasing the chance of developing CRC, following the inflammation-dysplasia-cancer sequence in IBD patients. Therefore, the aim of the present review was to analyze the correlation between changes in the gut microbiota and the development and maintenance of IBD, CRC, and IBD-associated CRC. Patients with IBD and CRC have shown reduced bacterial diversity and abundance compared to healthy individuals, with enrichment of Firmicute sand Bacteroidetes. Specific bacteria are also associated with the onset and progression of CRC, such as Fusobacterium nucleatum, E. coli, Enterococcus faecalis, Streptococcus gallolyticus, and ETBF. Future research can evaluate the advantages of modulating the gut microbiota as preventive measures in CRC high-risk patients, directly affecting the prognosis of the disease and the quality of life of patients.     

Dysplasia and colorectal cancer surveillance in inflammatory bowel disease

Introduction: Inflammatory bowel disease (IBD) patients are at an increased risk of developing colorectal cancer (CRC), a devastating complication of which intestinal dysplasia is the precursor. Considerable progress has been made to determine CRC risk in IBD, identification & management of dysplasia and preventative methods. Traditionally, surveillance colonoscopies with random colonic biopsies was used. However recent data suggests that chromoendoscopy is a better method of surveillance. Using 5-aminosalicylic acid agents primarily for chemoprevention is an ongoing debate however, when prescribed along with other strategies to control inflammation, their use is considered of benefit. This review presents current understanding of risk factors of neoplasia focusing on dysplasia and preventive strategies.

Areas covered: PubMed search was done using key words to assess current evidence. Along with genetics, risk factors, strategies that modify the risk of dysplasia, and CRC in IBD are discussed in detail.

Expert commentary: The role of our strategies in modifying CRC risk needs further assessment. Future research should aim to fill knowledge gaps such as high quality evidence for Chromoendoscopy and development of molecular markers for dysplasia detection. Our ultimate goal would be to eliminate CRC and is possible by better understanding of key pathogenic mechanisms in IBD.     

Colorectal cancer surveillance in inflammatory bowel disease: A critical analysis

Colonoscopic surveillance is advocated in patients with inflammatory bowel disease(IBD) for detection of dys-plasia. There are many issues regarding surveillance in IBD: the risk of colorectal cancer seems to be de-creasing in the majority of recently published studies, necessitating revisions of surveillance strategy; surveil-lance guidelines are not based on concrete evidence; commencement and frequency of surveillance, cost-effectiveness and adherence to surveillance have been issues that are only partly answered. The traditional technique of random biopsy is neither evidence-based nor easy to practice. Therefore, highlighting abnormal areas with newer technology and biopsy from these areas are the way forward. Of the newer technology, digital mucosal enhancement, such as high-definition white light endoscopy and chromoendoscopy(with magnification) have been incorporated in guidelines. Dyeless chromoendoscopy(narrow band imaging) has not yet shown potential, whereas some forms of digital chromoendoscopy(i-Scan more than Fujinon intelligent color enhancement) have shown promise for colonoscopic surveillance in IBD. Other techniquessuch as autofluorescence imaging, endomicroscopy and endocytoscopy need further evidence. Surveillance with genetic markers(tissue, serum or stool) is at an early stage. This article discusses changing epidemiology of colorectal cancer development in IBD and critically evaluates issues regarding colonoscopic surveillance in IBD.     

Obesity and novel management of inflammatory bowel disease

Obesity is prevalent within the inflammatory bowel disease(IBD) population,particularly in newly developed countries.Several epidemiological studies have suggested that 15%-40% of IBD patients are obese,and there is a potential role of obesity in the pathogenesis of IBD.The dysfunction of mesenteric fat worsens the inflammatory course of Crohn’s disease and may induce formation of strictures or fistulas.Furthermore,obesity may affect the disease course or treatment response of IBD.Given the incr...     

炎症性肠病相关性肝病的研究进展

炎症性肠病(inflammatory bowel disease,IBD)是一种累及回肠、结肠、直肠的特发性炎症性疾病,本病主要包括溃疡性结肠炎(ulcerative colitis,UC)和克罗恩病(Crohn’s disease,CD)。除常见的消化道症状外,研究发现IBD合并肝脏疾病较为常见,是IBD常见的肠外表现之一,其严重影响IBD的预后与转归。本文就IBD相关性肝病的分类和总结作一概述,以期为IBD及其肝脏病变的临床诊疗提供参考。     

Updates in therapeutic drug monitoring in inflammatory bowel disease

Biologics and immunomodulators (IMM) are generally considered the most effective therapies for the treatment of ulcerative colitis and Crohn’s disease. However, despite the efficacy of these therapies, many patients either have a primary lack of response or a secondary loss of response to these medications. Therapeutic drug monitoring (TDM) is a systematic approach to managing such patients. In this review, we summarize the latest data on TDM, including reactive and proactive TDM, in patients with inflammatory bowel disease on biologics and/or IMM.     

Anemia at the time of diagnosis of inflammatory bowel disease: Prevalence and associated factors in adolescent and adult patients

BackgroundThe prevalence, characteristic and determinants of anemia, at the time of inflammatory bowel disease (IBD) diagnosis have yet to be fully elucidated.MethodsRetrospective cross-sectional study. Analytical data and disease characteristics obtained upon diagnosis of 1278 IBD patients [Crohn’s disease/ulcerative colitis (CD/UC): 718/560] were collected.ResultsAnemia was present in 41.2% of patients at diagnosis (47% and 33.8% of CD and UC patients, respectively; p < 0.001), being severe in 5.5%. Iron deficiency anemia represented 69.6% of cases, with no differences between CD and UC. Female sex was the strongest risk factor for anemia in both CD and UC (OR 7.11; 95%CI 4.18–12.10 and 6.55; 95%CI 3.39–12.63, respectively), followed by elevated (≥2 mg/dL) C-reactive protein (OR 4.08; 95%CI 2.39–6.97 and 4.58; 95%CI 2.26–9.27, respectively). Current smoking was a risk factor for anemia in CD (OR 2.23; 95%CI 1.24–4.02), but a protective one in UC (OR 0.36; 95%CI 0.14–0.92). A penetrating CD behavior increased the risk of anemia (OR 3.34; 95%CI 1.36–8.21); in UC, anemia increased with disease extension (E2 + E3) (OR 1.80; 95%CI 1.13–2.86).ConclusionsFemale sex and disease activity are major determinants of anemia at IBD diagnosis. Anemia is associated with disease behavior in CD and with disease extension in UC.     

Comorbidity in inflammatory bowel disease

Patients with inflammatory bowel disease (IBD) can be affected by other unrelated diseases. These are called comorbid conditions, and can include any secondary health problem that affects a person suffering from a primary or main disease, and which is neither linked physiopathologically to the primary condition, nor is it due to the treatments used for the primary condition or to its long-term anatomical or physiological consequences. Different comorbid conditions, as well as their influence on IBD, are dis...     

Epidemiology of inflammatory bowel disease in South America: A systematic review

BACKGROUND The worldwide epidemiology of inflammatory bowel disease(IBD) is rapidly changing. Increasing Crohn's disease(CD) and ulcerative colitis(UC) incidence and prevalence have been recorded in developing regions such as Asia, Africa and Eastern Europe where it was previously thought to be uncommon. Whether this is also the case in South America is not well known. Demonstration that developing regions worldwide have increasing IBD incidence would indicate that environmental change plays a significant role in the development of IBD.AIM To report the incidence, prevalence and disease characteristics of CD and UC within the South American continent.METHODS A systematic review was conducted by searching published studies in major international and regional databases(MEDLINE, EMBASE and Scopus) between January 1990 and December 2018. Outcomes considered were incidence,prevalence, phenotype, environmental and genetic factors, ethnicity and gender.A pair of independent reviewers screened and reviewed all identified articles.RESULTS One hundred and sixty two citations were initially retrieved with 18 studies included in this systematic review. The majority of included studies were from Brazil(n =13, 72%). The incidence of UC ranged from 4.3-5.3/100000 personyears whilst the incidence of CD ranged from 0.74-3.5/100000 person-years.Prevalence ranged from 15.0-24.1/100000 inhabitants for UC and from 2.4-14.1/100000 inhabitants for CD. The incidence and prevalence of both UC and CD has increased significantly in Brazil over the past 21 years. Pancolitis was the most common disease distribution in patients with UC whilst colonic involvement was the most common distribution in CD. People residing in urbanareas were at higher risk of developing both CD and UC.CONCLUSION The IBD burden in South America is increasing at a rate possibly even greater than other developing regions around the world. There is a paucity of highquality epidemiological studies and further robust and representative data are required to further explore modifiable risk factors and disease phenotypes.     

肠易激综合征与炎症性肠病

近年发现,炎症性肠病(IBD)患者发病早期或缓解期时常表现为肠易激综合征(IBs)症状,且IBD与IBS的临床表现具有一定的相似性。因而IBS与IBD的相关性受到广泛的重视。此文就IBS与IBD的发病机制及临床相关性予以阐述,以期为临床个体化治疗提供借鉴。     

Endoscopic colorectal cancer surveillance in inflammatory bowel disease: Considerations that we must not forget

Inflammatory bowel disease (IBD), encompassing Crohn''s disease and ulcerative colitis, is a chronic immune-mediated inflammatory disease that primarily affects the gastrointestinal tract and is characterized by periods of activity and remission. The inflammatory activity of the disease involving the colon and rectum increases the risk of colorectal cancer (CRC) over the years. Although prevention strategies are evolving, regular surveillance for early detection of neoplasia as a secondary prevention strategy is paramount in the care of IBD patients. In this review article, we discuss the current evidence of the risks of developing CRC and evaluate the best available strategies for screening and surveillance, as well as future opportunities for cancer prevention.     

Monitoring inflammatory bowel disease during pregnancy:Current literature and future challenges

Inflammatory bowel disease has a high prevalence in women of childbearing age and can have a significant impact on pregnancy, from conceiving to carrying the pregnancy. Active disease during pregnancy is known to have negative effects on pregnancy outcomes; therefore, careful monitoring during this period is an important but challenging aspect of care and is crucial as it affects important management decisions. Recent data seems to suggest that endoscopy is a relatively safe procedure during all trimesters of pregnancy. Serum biomarkers such as C-reactive protein and fecal calprotectin are helpful non-invasive markers, but have shown conflicting results for correlation with disease activity in some initial studies. Further work is necessary to establish standard of care monitoring during pregnancy.     

Real-world treatment patterns and disease control over one year in patients with inflammatory bowel disease in Brazil

BACKGROUNDCrohn’s disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBDs) with a remission-relapsing presentation and symptomatic exacerbations that have detrimental impacts on patient quality of life and are associated with a high cost burden, especially in patients with moderate-to-severe disease. The Real-world Data of Moderate-to-Severe Inflammatory Bowel Disease in Brazil (RISE BR) study was a noninterventional study designed to evaluate disease control, treatment patterns, disease burden and health-related quality of life in patients with moderate-to-severe active IBD. We report findings from the prospective follow-up phase of the RISE BR study in patients with active UC or CD.AIMTo describe the 12-mo disease evolution and treatment patterns among patients with active moderate-to-severe IBD in Brazil.METHODSThis was a prospective, noninterventional study of adult patients with active Crohn’s disease (CD: Harvey-Bradshaw Index ≥ 8, CD Activity Index ≥ 220), inadequate CD control (i.e., calprotectin > 200 µg/g or colonoscopy previous results), or active ulcerative colitis (UC: Partial Mayo score ≥ 5). Enrollment occurred in 14 centers from October 2016 to February 2017. The proportion of active IBD patients after 9-12 mo of follow-up, Kaplan-Meier estimates of the time to mild or no activity and a summary of treatment initiation, discontinuation and dose changes were examined.RESULTSThe study included 118 CD and 36 UC patients, with mean ± SD ages of 43.3 ± 12.6 and 44.9 ± 16.5 years, respectively. The most frequent drug classes at index were biologics for CD (62.7%) and 5-aminosalicylate derivates for UC patients (91.7%). During follow-up, 65.3% of CD and 86.1% of UC patients initiated a new treatment at least once. Discontinuations/dose changes occurred in 68.1% of CD patients [median 2.0 (IQR: 2-5)] and 94.3% of UC patients [median 4.0 (IQR: 3-7)]. On average, CD and UC patients had 4.4 ± 2.6 and 5.0 ± 3.3 outpatient visits, respectively. The median time to first mild or no activity was 319 (IQR: 239-358) d for CD and 320 (IQR: 288-358) d for UC patients. At 9-12 mo, 22.0% of CD and 20.0% of UC patients had active disease.CONCLUSIONAlthough a marked proportion of active IBD patients achieved disease control within one year, the considerable time to achieve this outcome represents an unmet medical need of the current standard of care in a Brazilian real-world setting.     

HLA-DQ: Celiac disease vs inflammatory bowel disease

AIM To determine the genetic predisposition to celiacdisease(Ce D) in inflammatory bowel disease(IBD) patients by quantifying the frequency of Ce D-related human leucocyte antigen(HLA)(HLA-Ce D: HLA-DQ2 and-DQ8) in IBD patients globally, by type of IBD and gender, and by calculating the protective/risk contribution of these haplotypes in the development of the IBD disease.METHODS We conducted a prospective study with IBD patients from our Unit. Clinical information was gathered and blood was tested for HLA-CeD. The control group was made up of unrelated Valencian organ donors.RESULTS1034 subjects were analyzed: 457 IBD [207 ulcerative coliti(UC) and 250 Crohn's disease(CD)] patients and 577 healthy controls. 39% of the controls and 34% of the patients had HLA-Ce D(P = 0.0852). HLA-DQ2 was less frequent in UC patients(P = 0.0287), and HLA-DQ8 in CD(P = 0.0217). In women with UC, the frequency of DQ2.5 cis(DQB1*02:01-DQA1*05:01) was reduced ≥ 50% [P = 0.0344; preventive fraction(PF) = 13%]. PFs(7%-14%) were obtained with all HLACe D haplotypes. HLA DQB1*02:02-DQA1*02:01(HLADQ2.2) was more frequent in CD patients with respect to controls(P = 0.001) and UC patients(etiological fraction = 15%).CONCLUSION HLA-CeD is not more frequent in IBD patients, with an even lower frequency of HLA-DQ2 and-DQ8 in UC and CD respectively. HLA-DQ2.5 confers protection from the development of UC, especially in women, and HLADQ8 does so for the appearance of CD. HLA-DQ2.2 is present in 34% of the CD patients and may constitute a genetic risk factor for CD development.     

营养与炎症性肠病

营养和炎症性肠病的发病机制及治疗有密切的关系,深入研究两者的关系对临床有重要的意义。此文对饮食中的营养成分是否和发病有关、如何营养支持等问题作一简要概述。     

Declining use of combination infliximab and immunomodulator for inflammatory bowel disease in the community setting

AIM To describe trends of combination therapy (CT) of infliximab (IFX) and immunomodulator (IMM) for inflammatory bowel disease(IBD) in the community setting. METHODS A retrospective study was conducted of all IBD patients referred for IFX infusion to our community infusion center between 04/01/01 and 12/31/14. CT was defined as use of IFX with either azathioprine, 6-mercaptopurine, or methotrexate. We analyzed trends of CT usage overall, for Crohn's disease (CD) and ulcerative colitis (UC), and for the subgroups of induction patients. We also analyzed the trends of CT use in these groups over the study period, and compared the rates of CT use prior to and after publication of the landmark SONIC trial.RESULTS Of 258 IBD patients identified during the 12 year study period, 60 (23.3%) received CT, including 35 of 133(26.3%) induction patients. Based on the CochranArmitage trend test, we observed decreasing CT use for IBD patients overall(P 0.0001) and IBD induction patients,(P = 0.0024). Of 154 CD patients, 37(24.68%) had CT, including 20 of 77 (26%) induction patients.The Cochran Armitage test showed a trend towards decreasing CT use for CD overall(P 0.0001) and CD induction,(P = 0.0024). Overall, 43.8% of CD patients received CT pre-SONIC vs 7.4% post-SONIC (P 0.0001). For CD induction, 40.0% received CT preSONIC vs 10.8% post-SONIC(P = 0.0035). Among the 93 patients with UC, 19 (20.4%) received CT. Of 50 induction patients, 14 (28.0%) received CT. The trend test of the 49 patients with a known year of induction again failed to demonstrate any significant trends in the use of CT(P = 0.6). CONCLUSION We observed a trend away from CT use in IBD. A disconnect appears to exist between expert opinion and evidence favoring CT with IFX and IMM, and evolving community practice.     

IL-17基因多态性与中国汉族人群炎症性肠病的关系

目的:研究IL-17A和IL-17F的5个多态性位点与中国汉族人炎症性肠病之间的关系.方法:采用病例-对照研究方法,收集确诊的溃疡性结肠炎(ulcerative colitis,UC)和克罗恩病(Crohn’s disease,CD)患者共350例(UC270例;CD80例),健康对照组268例,收集外周血标本2mL,提取DNA,运用LDR(ligasedetection reaction allelic)技术进行多态性检测.采用SPSS17.0软件进行数据分析.结果:CD患者中IL-17F(rs763780,7488T/C)突变等位基因C的频率明显高于对照组(13.8%vs8.4%,P=0.044,OR=1.74,95%CI1.01-2.99).在亚型分析中,rs763780基因多态性与CD病变范围有关,突变等位基因C在CD回结肠型患者中的频率明显高于对照组(P=0.02).IL-17A(rs2275913,G-197A)与UC患者疾病的严重程度有弱相关性,含有突变基因A的患者倾向于临床轻型.IL-17F(rs763780,7488T/C)多态性与U C患者发病年龄之间有弱相关性,T/C基因型患者趋向于年轻型(P=0.046).结论:IL-17F rs763780基因多态性与CD易感性之间有弱相关性,在亚组分析中发现rs763780与CD的病变范围和UC的发病年龄有关.IL-17A rs2275913基因多态性与UC疾病严重程度呈负相关.