Clinical study of the relationship between inflammatory bowel diseases and colorectal neoplasms

OBJECTIVE: To investigate the incidence of colorectal cancer in inflammatory bowel disease (IBD) patients and its risk factors. METHODS: Data on 513 patients in the last 10 years from Ruijin Hospital were collected. Their medical histories were put in database and analyzed including their socio‐demographic features, pathogenetic conditions, diagnostic methods, possible related risk factors, treatment and outcome. RESULTS: Among the 513 were 242 with ulcerative colitis (UC), among whom four patients developed cancers and four had precancerous lesions. None of the 271 CD patients developed cancer. The incidence of both cancer and precancerosis in the UC patients was 1.65%. Through multifactorial logistic regression analysis, loss of weight, other disease complications and frequent relapses were proved to be the most probable risk factors. CONCLUSION: The incidence of IBD has kept on rising in recent years. Clinically, UC patients have more probability of developing colorectal cancer than CD patients. The main risk factors of developing colorectal cancer in UC patients are frequent relapses, weight loss and other complications.     

Current status and future perspectives of leukocytapheresis for inflammatory bowel disease

Ulcerative colitis (UC) and Crohn's disease (CD) comprise the idiopathic inflammatory bowel diseases (IBD) of the gut. The etiology of IBD is poorly understood, but an autoimmune disturbance has been suggested to play an important role in this incurable disease. Extracorporeal leukocytapheresis (CAP) is an additional adjunct for IBD patients refractory to other conventional therapies, including steroids. The primary aim of CAP should be to suppress such unwanted immunological response by removing circulating inflammatory cells from the blood stream. The first decade has been passed since CAP was approved by Japanese social health insurance policy. It is therefore now an appropriate opportunity to upgrade and summarize our current understandings and/or future perspectives of this unique non-pharmacological and non-surgical strategy for IBD patients. According to several clinical and basic research reports, an early introduction of CAP should produce higher efficacy as compared with CAP applied sometime after a clinical relapse. Likewise, CAP therapy adjusted to patients' body-weight as well as two treatment sessions per week (intensive regimen) should benefit the efficacy rate. The etiology of IBD is not fully elucidated yet. As a result, the major therapeutic strategies in the Western world have been immunosuppressive therapy, including biologics. CAP is an unusual treatment modality for IBD because it seems to have both effectiveness and safety, which should generally be balanced in this type of illness. We now have to develop future strategies with and without combining biologics to improve the quality of life of IBD patients.     

Management of inflammatory bowel disease in adults

Optimal care of the inflammatory bowel diseases, Crohn's disease and ulcerative colitis, requires a broad understanding of disease pathophysiology and therapeutic alternatives. The goals of therapy are accurate diagnosis and timely treatment to both induce and maintain a clinical remission and improve patient quality of life. Most patients can be adequately treated using a combination or aminosalicylates, antibiotics, and corticosteroids, though many patients with Crohn's disease will require immunomodulators, such as azathioprine or 6-mercaptopurine. The development of novel biologic therapies, particularly infliximab, have dramatically improved our ability to medically manage more severe Crohn's disease and ulcerative colitis patients. This review will focus on the medical management of inflammatory bowel disease in adults.     

Progression of inflammatory bowel disease in China

The epidemiology and phenotype of inflammatory bowel disease (IBD) in the Chinese population is not well-known. We performed a comprehensive search of the Chinese biomedical literature database from 1989 to 2007 using the following key words: inflammatory bowel disease (IBD), ulcerative colitis (UC), Crohn's disease (CD). The investigation of hospitalized IBD patients from 1990 to 2003 was also carried out in 23 medical centers of 11 cities over China. There are some notable epidemiological and phenotypical differences between Chinese IBD and Caucasian IBD, including a lack of familial clustering, male predominance, a relatively later onset of the illness with no second peak age occurrence after 50 years old, a milder clinical course, less extra-intestinal manifestations and complications, and less fistulous and peri-anal complications in Chinese CD. The data indicate an increased incidence of IBD in China with many complicated clinical problems, which offers potential opportunities to study the disease prospectively and identify the etiological factors, leading also to the better management of this disease in China.     

Microbiome and metabolome in inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic gastrointestinal disease of unknown etiology, involving complex interactions between the gut microbiome and host immune response. The microbial dysbiosis is well documented in IBD and significantly influences the host metabolic pathways. Thus, a metabolomic fingerprint resulting from the influence of gut dysbiosis in IBD could aid in assessing the disease activity. PubMed, Medline, Science Direct, and Web of Science were searched for studies exploring the association between microbiome and metabolome in IBD patients in the last 5 years. Additionally, references of cited original articles and reviews were further assessed for relevant work. We provide a literature overview of the recent metabolomic studies performed on patients with IBD. The findings report alterations in the metabolite levels of these patients. We also discuss the gut dysbiosis observed in IBD and its influence on host metabolic pathways such as lipids, amino acids, short-chain fatty acids, and others. IBD, being a chronic idiopathic disease, requires routine monitoring. The available non-invasive markers have their limitations. The metabolite changes account for both dysbiosis and its influence on the host's immune response and metabolism. A metabolome approach would thus facilitate the identification of surrogate metabolite markers reflecting the disease activity.     

Visualising E-selectin in the detection and evaluation of inflammatory bowel disease

Background—Vascular endothelial E-selectin expression is induced by proinflammatory cytokines andcontributes to accumulation of leucocytes in tissues.
Aims—To investigate the role ofE-selectin in inflammatory bowel disease (IBD).
Methods—E-selectin expression wasassessed in patients with ulcerative colitis and Crohn's disease bymeasuring the concentration of circulating soluble E-selectin(sE-selectin) using ELISA, by immunohistochemistry of colonic biopsyspecimens, and by abdominal immunoscintigraphy after injectingradiolabelled F(ab')₂ fragment of a monoclonalanti-E-selectin antibody. The value of scintigraphy usinganti-E-selectin was judged by a prospective comparative study ofautologous leucocyte scanning and E-selectin antibody scanning in 17 patients with IBD.
Results—Circulating sE-selectin waselevated in patients with clinically active disease. Tissue expressionof E-selectin was enhanced in patients with active inflammation, withweak or absent expression in inactive disease and healthy controls.In-111 labelled anti-E-selectin scintiscans were compared with Tc-99mlabelled leucocyte scans performed 24 hours earlier. Twelve patientshad areas of active inflammation on leucocyte scan while 11 patients had positive E-selectin scans. The results of the two scans were concordant in 14 patients, with those positive for both (10/17) showingsimilar disease localisation and extent.
Conclusions—Tissue E-selectinand circulating sE-selectin are increased during active inflammatorybowel disease. Anti-E-selectin imaging with radiolabelled monoclonalantibody identified areas of inflammation in Crohn's disease andulcerative colitis. The technique should prove useful clinically foridentifying the site and extent of disease.

Keywords:E-selectin; inflammatory bowel disease; Crohn'sdisease; ulcerative colitis

     

Diagnostic misclassification reduces the ability to detect linkage in inflammatory bowel disease genetic studies.

BACKGROUND: Linkage data have now identified several inflammatory bowel disease (IBD) susceptibility loci but these data have not been consistently replicated in independent studies. One potential explanation for this is the possibility that patients enrolled in such studies may have been erroneously classified with respect to their diagnosis. AIMS: To determine the rate and type of misclassification in a large population of individuals referred for participation in an IBD genetics study and to examine the effect of diagnostic misclassification on the power to detect linkage. METHODS: The medical records of 1096 patients entered into an IBD genetics programme were reviewed using standardised diagnostic criteria. The original patient reported diagnoses were changed, if necessary, based on review, and the reasons for the change in diagnosis were recorded. To evaluate the effect of misclassification on linkage results, simulations were created with Gensim and analysed using Genehunter to evaluate a model for IBD inheritance. RESULTS: Sixty eight of 1096 (6.2%) individuals had a change in diagnosis from that originally reported. The majority of changes were patients with either Crohn's disease or ulcerative colitis who were determined not to have IBD at all. The principal reasons for changes to the original diagnosis were discordance between the patients' subjective reports of diagnosis and actual clinical history, endoscopic, or pathological results; a change in disease pattern over time; and insufficient information available to confirm the original diagnosis. A 10% misclassification rate resulted in 28.4% and 40.2% loss of power to detect a true linkage when using a statistical model for a presumed IBD locus with lambda(s) values of 1.8 and 1.3, respectively. CONCLUSIONS: Diagnostic misclassification occurs in patients enrolled in IBD genetic studies and frequently involves assigning the diagnosis of IBD to non-affected individuals. Even low rates of diagnostic misclassification can lead to significant loss of power to detect a true linkage, particularly for loci with modest effects as are likely to be found in IBD.     

Comparison of clinical characteristics and management of inflammatory bowel disease in Hong Kong versus Melbourne

Background and Aim: Inflammatory bowel disease (IBD), common in Melbourne, was rare but is now increasing in incidence in Hong Kong (HK). To investigate whether these are the same diseases in the West and East, potential causes of changing incidence, and to plan resource needs, an appreciation of clinical characteristics in contrasting populations is essential. Methods: Disease characteristics were collected from prospectively populated IBD databases in two specialist centers in Melbourne, Australia and HK. Results: Of 795 patients (Crohn's disease [CD] : ulcerative colitis [UC] Melbourne 272:159 and HK 161:203), the age of diagnosis was higher, there were proportionally more male patients with CD but no UC sex difference, fewer patients were current or ex‐smokers (CD 8% vs 50%; UC 17% vs 35%) and a family history of IBD was less common (2% vs 11%; P < 0.001) in HK compared to Melbourne. Stricturing and perianal CD were more common in HK (12% vs 6%; P < 0.001; and 29% vs 16%; P = 0.001, respectively). In HK for UC, more patients had extensive disease at diagnosis (42% vs 22%) but colectomy was less common (7% vs 20%; P < 0.001). In Melbourne there was greater steroid use at diagnosis and patients were more likely to receive an immunomodulator or anti‐tumor necrosis factor agent. Conclusions: IBD in HK was diagnosed at an older age, and had more complicated disease behavior than in Melbourne. Medical therapy, however, was less intense in HK. These differences may relate to real differences in disease or delayed diagnosis due to late presentation and less disease recognition in HK.     

Proteomics and metabolomics in inflammatory bowel disease

Genome‐wide studies in inflammatory bowel disease (IBD) have allowed us to understand Crohn's disease and ulcerative colitis as forms of related autoinflammatory disorders that arise from a multitude of pathogenic origins. Proteomics and metabolomics are the offspring of genomics that possess unprecedented possibilities to characterize unknown pathogenic pathways. It has been about a decade since proteomics was first applied to IBD, and 5 years for metabolomics. These techniques have yielded novel and potentially important findings, but turning these results into beneficial patient outcomes remains challenging. This review recounts the history and context of clinical IBD developments before and after proteomics and metabolomics IBD in this field, discusses the challenges in consolidating high complexity data with physiological understanding, and provides an outlook on the emerging principles that will help interface the bioanalytical laboratory with IBD prognosis.     

The emerging global epidemic of paediatric inflammatory bowel disease – causes and consequences

Two decades ago, paediatric inflammatory bowel disease (IBD) drew only modest interest from the international paediatric community. Since then, dramatically globally increasing incidence rates have made childhood‐onset IBD a priority for most paediatric gastroenterologists. The emerging pandemia of paediatric IBD has fuelled a quest to identify the recent changes in early life exposures that could explain the increasing risk for IBD amongst today's children. Treatment of children with IBD should aim for symptom control but should also target restoration of growth and prevention of pubertal delay. The paediatric IBD phenotype seems to be characterized by more extensive disease location, and some comparative studies have suggested that childhood‐onset IBD also represents a more severe phenotype than the adult‐onset IBD form. In this review, we analyse recent global incidence trends of paediatric IBD. We present an update on the known and suggested risk factors that could explain the emerging global epidemia of paediatric IBD. We also draw attention to differences in treatment between children and adults with IBD. Finally, we highlight latest follow‐up studies that question the proposed dynamic and aggressive nature of childhood‐onset IBD.     

Inflammatory bowel disease: progress and current concepts of etiopathogenesis

Over the past few years, none of the numerous conditions that are grouped under the broad designation of 'chronic inflammatory or autoimmune disorders' has undergone as much scientific and clinical progress as the two main forms of inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC). Progress has occurred in all major areas relevant to IBD pathogenesis, which include the external environment, genetics, microbial factors, and the immune system. This review presents an update on the specific major advances that have occurred in each of these four areas, briefly discusses the therapeutic implications of the observed progress, and points out the additional work that needs to be accomplished in the next few years to reach a full understanding of IBD etiopathogenesis.     

Recent developments in the treatment of inflammatory bowel disease

Crohn's disease and ulcerative colitis are chronic inflammatory bowel diseases that have been treated with corticosteroids, 5‐aminosalicates and thiopurines, but therapeutic options have been broadened with the arrival of anti‐tumor necrosis factor antibodies. In this article we reviewed the current evidence‐based approach to inflammatory bowel disease, the modifications that have been made to existing therapies and discussed new drugs that have shown success in clinical trials. The new drugs discussed here are those that disturb lymphocyte homing to the gut (natalizumab, vedolizumab and anti‐mucosal addressin cellular adhesion molecule); one that blocks interleukin (IL)‐12 as well as the IL‐23/T helper 17 (Th17) axis (ustekinumab) and one that blocks the signaling of multiple cytokines (tofacitinib).     

Granulocyte,monocyte/macrophage apheresis for inflammatory bowel disease: The first 100 patients treated in Scandinavia

Objective. Selective leukocyte apheresis is a new type of non-pharmacological treatment for patients with active ulcerative colitis and Crohn's disease. Preliminary data have indicated that this type of therapy is safe and efficacious, and large sham-controlled studies are currently in progress. In Scandinavia, a substantial number of patients with chronic inflammatory bowel disease have already received leukocyte apheresis on a compassionate use basis and the aim of this study was to report the clinical outcome and adverse events in the first patients treated. Material and methods. Clinical details of the first consecutive 100 patients with inflammatory bowel disease treated with granulocyte, monocyte/macrophage (Adacolumn) apheresis in Scandinavia were prospectively registered. Median length of follow-up was 17 months, (range 5–30). Results. The study population comprised 52 patients with ulcerative colitis, 44 patients with Crohn's disease and 4 patients with indeterminate colitis. In 97 patients the indication for Adacolumn treatment was steroid-refractory or steroid-dependent disease. Clinical remission was attained in 48% of the patients with ulcerative colitis, and an additional 27% had a clinical response to the apheresis treatment. The corresponding figures for patients with Crohn's disease were 41% and 23%, respectively. Complete steroid withdrawal was achieved in 27 out of the 50 patients taking corticosteroids at baseline. Adverse events were reported in 15 patients and headache was most frequently reported (n=7). Conclusions. Granulocyte, monocyte/macrophage apheresis treatment seems to be a valuable adjuvant therapy in selected patients with refractory inflammatory bowel disease. The risk for toxicity or severe adverse events appears to be low.     

Body mass index and risk of inflammatory bowel disease: A systematic review and dose‐response meta‐analysis of cohort studies of over a million participants

The relationship between body mass index (BMI) and risk of inflammatory bowel disease (IBD) is controversial. We performed a dose‐response meta‐analysis to investigate the association between BMI and risk of incident ulcerative colitis (UC) and Crohn's disease (CD) using prospective cohort studies. A systematic search was conducted in MEDLINE/PubMed, SCOPUS, Cochrane, and Web of Science databases from inception to January 2019. DerSimonian and Laird random‐effects model was used to estimate combined hazard ratios (HRs). Overall, 882 articles were screened, and 42 full‐text articles were reviewed for inclusion using the study eligibility criteria. Five studies evaluated the association between BMI and IBD with 1 044 517 participants. Pooled results showed a significant association between participants affected by obesity and risk of CD (HR: 1.42, 95% CI: 1.18‐1.71, I²: 0.00). There was a significant nonlinear association between BMI and risk of CD (P = .01, coeff = 0.5024). Pooled results did not show any significant association between being underweight and risk of UC (HR: 1.07, 95% CI: 0.96‐1.19, I²: 0.00) or CD (HR: 1.11, 95% CI: 0.93‐1.31, I²: 12.8). There was no difference in the risk for UC among participants affected by obesity compared with participants categorized as having normal BMI (HR: 0.96, 95% CI: 0.80‐1.14, I²: 8.0). This systematic review and meta‐analysis identified significant dose‐response relationship between being affected by obesity, as a risk factor, and incidence of CD.     

Use of complementary and alternative medicine in patients with inflammatory bowel disease: results of a cross-sectional study in Norway

Abstract

Objective. To determine the proportion of complementary and alternative medicine (CAM) use in patients with inflammatory bowel disease (IBD) and to identify demographic and clinical factors that are associated with CAM use. Material and methods. In this cross-sectional study design, patients with confirmed diagnosis of ulcerative colitis (UC) or Crohn's disease (CD), and ≥18 years old, attending outpatient clinics at 14 hospitals in Norway were eligible to complete questionnaires including demographics, clinical variables, and the International CAM Questionnaire (I-CAM-Q). Results. Of 460 patients included in the study, 430 had evaluable questionnaires (response rate 93%). Forty-nine percent (95% CI: 44–54) had used some type of CAM within the past 12 months. CAM services were utilized by 27% (95% CI: 23–31) of the patients, 21% (95% CI: 16–23) reported use of CAM products, and 28% (95% CI: 23–31) used CAM self-help practices. The most common pattern of CAM use was to combine CAM services and CAM products. Significantly, more UC patients (56%) than CD patients (44%) reported CAM use, p = 0.03. In UC, only the presence of at least one comorbid condition was directly related to CAM use. In CD, being a woman, being aged 31–50 years, having a higher education level, and experiencing adverse drug reactions from IBD medication were factors independently associated with the use of CAM. Conclusion. Use of CAM was common among IBD patients attending outpatient clinics. Both demographic and clinical factors were associated to CAM use, but the factors differed in their significance for UC and CD.