Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022104 (irritable bowel syndrome)
 8,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lectin binding of goblet cell mucin in human colonic mucosa was studied in patients with irritable bowel syndrome, colorectal malignancy and ulcerative colitis using plant lectins, Dolichos biflorus agglutinin (DBA) and peanut agglutinin (PNA). Normal colonic mucosa demonstrated a strong binding with DBA (100%) but did not bind to PNA at all. Colonic carcinomas showed strong PNA binding (7 of 15 biopsies) while DBA binding was absent in 14 of 15 biopsies. The transitional mucosa showed reduced or absent DBA binding in 6 and positive PNA binding in 2 of 15 biopsies. During the active phase of ulcerative colitis, there was a loss of DBA binding in 10 of 15 biopsies, which was restored during remission in all. One biopsy with severe dysplasia showed PNA binding. It is concluded that normal colorectal mucosa binds DBA strongly but not PNA. Malignant tissue and transitional mucosa reveal PNA binding often, with decreased DBA binding. In ulcerative colitis DBA binding decreases during phases of activity.
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PMID:Lectin binding in colorectal mucosa. 291 16

Individuals with chronic ulcerative colitis are at increased risk of developing colorectal carcinoma, particularly if there is long-standing disease or extensive colitis. It is generally accepted that the risk of colorectal cancer does not begin until 8 to 10 years after the time of diagnosis of ulcerative colitis. Thereafter it increases by approximately 0.5% to 1.0% per year. In patients with Crohn's disease, the risk of malignancy is smaller and less well defined. The most significant predictor of the risk of malignancy in patients with inflammatory bowel disease is the presence of dysplasia in colonic biopsies. There is considerable controversy in the literature regarding the efficacy of colonoscopic surveillance programs and the role of prophylactic surgery to prevent colorectal cancer. Surveillance certainly fails to detect carcinoma in some patients who are having regular colonoscopy. Concerns have also been raised as to the cost-benefit of colonoscopic surveillance in patients with colitis. Randomized controlled trials of surveillance programs are highly unlikely in view of the low prevalence of IBD in the population, the long period of observation required, and the probability of contamination of surveillance programs by colonoscopy for assessment of disease activity. Despite the lack of clear guidelines, surveillance colonoscopy and biopsy continues to be widely practiced. Research is proceeding to identify genetic and biochemical markers that may prove clinically useful for predicting cancer risk. At present, however, surveillance programs are likely to continue according to institutional practice. It is important for those participating in such programs to be aware of the limitations of colonoscopy and biopsy as a means of reducing the risk of cancer in inflammatory bowel disease.
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PMID:Cancer and inflammatory bowel disease: bias, epidemiology, surveillance, and treatment. 952 16

Dysplasia is a morphological term that ethymologically means 'malformation'. For the definition of inflammatory bowel disease-related dysplasia, the nature and origin of the malformation are stressed and the lesion is defined as an epithelial malformation that is unequivocally neoplastic but noninvasive. The use of a precise definition is necessary because of the clinical consequences related to the finding of dysplasia in IBD. The microscopic diagnosis of dysplasia, however, remains difficult. Clinically, it is important to make a proper differential diagnosis between polypoid IBD-related dysplasia and sporadic adenoma occurring in IBD, and between therapy-related 'pseudodysplasia' and genuine dysplasia. When dysplasia is diagnosed, a second opinion may be indicated because of the clinical consequences. Additional techniques to search for genetic defects associated with carcinogenesis can help to support the diagnosis. They can identify changes in DNA content and molecular changes resulting from defects of genes controlling cell proliferation and death or tissue structure. These changes can, however, be absent, appear early or late in the transition from normality toward dysplasia and cancer, or appear during repair. Positive findings indicate an increased cancer risk, but the magnitude of the risk remains to be defined. A positive diagnosis of genuine dysplasia necessitates clinical action - either follow-up of the patient or treatment. In practice, treatment means surgery because dysplasia can be a precursor and/or a marker of malignancy, except for sporadic adenomas, which can be removed locally.
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PMID:Dysplasia in inflammatory bowel diseases: definition and clinical impact. 1054 55

With the heterogeneous clinical presentation of IBD, endoscopy plays an integral role in the initial diagnosis of ulcerative colitis and Crohn's disease. Although radiographic tests often are supplemental in the work-up of IBD, colonoscopy with biopsy is the test of choice if IBD is suspected and is more sensitive than radiographic tests. Endoscopic features can be helpful in differentiating ulcerative colitis and Crohn's disease. Currently the only mode for detecting dysplasia and stratifying the risk of developing colorectal cancer is through complete colonoscopy with multiple biopsy specimens. Complications of IBD can be managed effectively with endoscopic therapy. The role of endoscopic ultrasound and future developments in endoscopic therapy need to be defined by future studies.
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PMID:Endoscopy in inflammatory bowel disease. 1212 27

The risk of cancer in IBD is real and is a cause of anxiety and concern among patients and practitioners. Current modalities for detecting dysplasia in IBD are crude and insensitive and subject to observer and sampling bias. This evidence-based review confirms a significant increased risk for colorectal cancer among patients with pancolonic UC and, to a lesser extent, in patients with left-sided disease. Risk increases with longer duration of disease; early age at diagnosis; coexisting PSC; and, perhaps, a family history of colorectal cancer. Physicians must pay greater attention to the manner in which they implement surveillance colonoscopies, including paying heed to the location and number of biopsy specimens required to maximize the benefit. With respect to CD, the evidence suggests that patients with extensive colonic involvement of long duration carry a similar risk of colorectal cancer to patients with UC and should be considered candidates for surveillance colonoscopy.
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PMID:Cancer in inflammatory bowel disease. An evidence-based analysis and guide for physicians and patients. 1212 35

Colorectal cancer is an important, and often dreaded, consequence of long-standing UC and Crohn's colitis. Surveillance colonoscopy, despite its limitations, is beneficial for detecting earlier stage cancers and, probably, mortality reduction. Agents such as anti-inflammatory medications, folic acid, and ursodeoxycholic acid show promise for chemoprevention in this disease. Future research will help to define better the natural history of dysplasia in IBD, and to determine how molecular approaches may be integrated into surveillance programs to reduce CRC risk.
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PMID:Cancer prevention in patients with inflammatory bowel disease. 1248 82

Ulcerative colitis and Crohn's disease (together known as Inflammatory Bowel Disease or IBD) are both associated with increased risk for colorectal cancer. Although it is conventional to emphasise differences between IBD-associated and sporadic colon cancer, such as a lower rate of Adenomatosis Polyposis Coli mutations and earlier p53 mutations, IBD-associated cancer has a similar dysplasia-cancer sequence to sporadic colon cancer, similar frequencies of major chromosomal abnormalities and of microsatellite instability and similar glycosylation changes. This suggests that IBD-associated colon cancer and sporadic colon cancer might have similar pathogenic mechanisms. Because the normal colon is arguably in a continual state of low-grade inflammation in response to its microbial flora, it is reasonable to suggest that both IBD-associated and sporadic colon cancer may be the consequence of bacteria-induced inflammation. We have speculated that the glycosylation changes might result in recruitment to the mucosa of bacterial and dietary lectins that might otherwise pass harmlessly though the gut lumen. These could then lead to increased inflammation and/or proliferation and thence to ulceration or cancer. The glycosylation changes include increased expression of onco-fetal carbohydrates, such as the galactose-terminated Thomsen-Friedenreich antigen (Gal beta1,3GalNAc alpha-), increased sialylation of terminal structures and reduced sulphation. These changes cannot readily be explained by alterations in glycosyltransferase activity but similar changes can be induced in vitro by alkalinisation of the Golgi lumen. Consequences of these changes may be relevant not only for cell-surface glycoconjugates but also for intracellular glycoconjugates.
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PMID:Altered glycosylation in inflammatory bowel disease: a possible role in cancer development. 1282 Jul 18

Inflammatory conditions are characterized by activation of the transcription factor nuclear factor kappa B (NF-kappaB), resulting in the expression of NF-kappaB-regulated, inflammation-related genes, such as inducible nitric oxide synthase (iNOS) and cyclo-oxygenase-2 (COX-2). Expression of these genes contributes to the survival of cells. Indeed, exposure to pro-inflammatory cytokines in the absence of NF-kappaB activation leads to apoptosis.(1,2) Chronic inflammatory conditions are accompanied by constitutive activation of NF-kappaB and hence, to the continuous expression of pro-survival genes, as has been observed in chronic gastritis.(3) Although beneficial for the survival of cells during exposure to inflammatory stress, the continuous activation of NF-kappaB may also pose a risk: cells with a pro-survival phenotype may give rise to continuously proliferating cells and may thus be tumorigenic. Progression to a malignant phenotype of these cells will most likely involve additional changes in the expression of non-NF-kappaB regulated genes e.g. a shift in the balance of pro- and anti-apoptotic genes towards a more anti-apoptotic phenotype. Literature on inflammation-related genes and the apoptotic balance in pre-malignant and malignant conditions in the gastro-intestinal tract is still scarce and conflicting. In this review, we aim to give an overview of the existing literature and we will focus on inflammation- and apoptosis-related genes in the sequence of normal epithelium-inflamed epithelium-metaplasia-dysplasia-cancer in the gastrointestinal tract, in particular esophagus (Barrett's esophagus: BE), stomach (gastritis) and colon (inflammatory bowel disease: IBD).
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PMID:Chronic inflammation, apoptosis and (pre-)malignant lesions in the gastro-intestinal tract. 1533 51

Colorectal cancer (CRC) is still a disease with a high incidence and mortality. Prevention of (pre-) cancerous lesions of CRC by endoscopic screening is promising, but costs are high and identification of high-risk populations is difficult. Since screening both average-risk and high-risk populations for CRC has its logistic and financial limitations, new primary prevention strategies are sought. Substantial evidence has shown that non-steroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors can reduce the incidence and mortality of CRC. However, long-term use of NSAIDs is associated with substantial gastrointestinal toxicity and may cause an exacerbation in IBD patients. Selective COX-2 inhibitors, with a better toxicity profile and no flare-up in IBD disease activity, are therefore attractive candidates for prevention. Chemoprevention with low-dose aspirin can be considered for individuals carrying a high risk for CRC. Folate supplementation is beneficial to the folate-depleted patients, since significant risk reductions for CRC are reported. Moreover, it might be applicable to the general population because it is safe, inexpensive and protects against vascular diseases. In line with drugs beneficial for multiple disease entities, statins have recently been proposed to reduce CRC risk. Ursodeoxycholic acid has been shown to decrease the incidence of colonic dysplasia in patients with ulcerative colitis and PSC and possibly reduces recurrence rates of polyps in general. Unfortunately, prospective randomized trials, in both high-risk and general population, are not available and the evidence is still controversial. Furthermore, cumulative epidemiological and observational data suggest the potential role of hormones as a chemoprotective agent. An increase in CRC in females with an early menopause, as well as a decrease of CRC in women with hormone replacement therapy justify further research into this issue. In IBD patients, both the severity and duration of the inflammation are the most evident risk factors for the development of dysplasia and subsequently cancer. Remission of inflammation, clinically, endoscopically and histologically, in IBD is the major goal. Long-term use of 5-aminosalicylates (5-ASA) has been shown to decrease the incidence of CRC and may hold the best promise as a chemoprotective agent in IBD. In parallel with primary prevention strategies in vascular medicine, the aim might be to postpone adenoma formation, for instance for 10 years, thereby achieving a significant risk reduction for CRC. In current practice, folate supplementation along with low-dose aspirin use in high-risk patients may be most attractive candidates, while future studies will have to clarify the role of these and other chemoprotective agents.
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PMID:Chemoprevention for colon cancer: new opportunities, fact or fiction? 1678 36

There remain technical challenges to the accurate prediction and diagnosis of neoplasia in IBD; therefore, prevention strategies are based on limited evidence and instead, consensus opinions and guidelines. Existing guidelines and published expert opinions are in agreement that given the increased risk of cancer in IBD and well-described associated risks, prevention strategies are warranted. The preponderance of existing prevention is focused on secondary prevention by performance of screening and surveillance colonoscopies with random biopsies to identify neoplasia and trigger surgical resection for prevention of invasive cancer and death. Substantial technical and practical challenges remain, however, and there is a great need for improved understanding of the compounded risks of neoplasia, the natural history of dysplasia, and more accurate detection and diagnostic techniques. A future approach to prevention is likely to stratify patients based on individualized risks that include, among things, the histologic degree of inflammation present. In meantime, existing guidelines should be emphasized and ongoing education of clinicians and patients must occur.
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PMID:Surveillance for cancer and dysplasia in inflammatory bowel disease. 1695 42


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