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Acute and late toxicity of patients with inflammatory bowel disease undergoing irradiation for abdominal and pelvic neoplasms.

PURPOSE: Little data exists in the medical literature describing the response of patients with inflammatory bowel disease (IBD) to abdominal and pelvic irradiation. To clarify the use of this modality in this setting, this study assesses the short- and long-term tolerance of 28 patients with IBD to abdominal and pelvic irradiation. METHODS AND MATERIALS: From 1970 to 1999, 28 patients with IBD (10 patients-Crohn's disease, 18 patients-ulcerative colitis) were identified and underwent external beam abdominal or pelvic irradiation. Mean follow-up time after radiation therapy was 32 months. Patients were treated either by specialized techniques (16 patients) to minimize small and large bowel irradiation or by more conventional approaches (12 patients). Acute and late toxicity was scored. RESULTS: The overall incidence of severe toxicity was 46% (13/28 patients). Six of 28 patients (21%) experienced severe acute toxicity necessitating cessation of radiation therapy. Late toxicity requiring hospitalization or surgical intervention was observed in 8 of 28 patients (29%). One patient experienced both an acute as well as late toxicity. For patients undergoing radiation therapy by conventional approaches, the 5-year actuarial rate of late toxicity was 73%. This figure was 23% for patients treated by specialized techniques (p = 0.02). CONCLUSIONS: Because of the potentially severe toxicity experienced by patients with IBD undergoing abdominal and pelvic irradiation, judicious use of this modality must be employed. Definition of IBD location and activity as well as careful attention to irradiation technique may allow treatment of these patients with acceptable rates of morbidity.

Abdomen↗

The role of nuclear medicine in inflammatory bowel disease. A review with experiences of aspecific bowel activity using immunoscintigraphy with 99mTc anti-granulocyte antibodies.

UNLABELLED: The diagnosis of inflammatory bowel disease (IBD) needs a complex diagnostic work-up. Beside verifying the disease itself, it is fundamental to assess disease extent and activity and to detect associated complications, to find the most effective treatment and for follow up. Scintigraphy with radiolabelled leukocytes is able to provide a complete survey of the whole intestinal tract, both the small and large bowel, and detects septic complications successfully with negligible risk. Radionuclide procedures are useful in establishing or ruling out IBD in patients with intestinal complaints, in assessing disease severity, and in the evaluation of extraintestinal septic complications. Widely available radionuclide procedures are discussed, i.e. scintigraphy by 111Indium oxime or 99mTechnetium HMPAO labelled white blood cells and immunoscintigraphy with 99mTc anti-granulocyte antibodies. Advantages and disadvantages of all three methods are stressed out. PATIENTS AND METHODS: The immunoscintigraphies with 99mTc anti-granulocyte antibodies (ANTI-GRANULOCYTE(R) BW 250/183) of 27 patients with suspicion of IBD were retrospectively analysed. Planar anterior and posterior images were obtained 4 and 24 h postinjection, respectively. The bowel was divided into six segments and the activity was visually graded with reference to bone marrow in each segments. The scans were compared with the results of radiological and endoscopical investigations. The diagnosis of IBD was proved or ruled out by means of enteroclysis, large bowel enema or endoscopy. RESULTS: In the 27 patients, 74 bowel segments with increased activity were detected. In the case of 30 segments in 16 patients, bowel inflammation was revealed by the other methods (true positives). In the case of 44 bowel segments, no underlying bowel inflammation could be verified, and these activities were regarded as aspecific activity. We could not differentiate between true positive and aspecific activity based on scan pattern or intensity. DISCUSSION: These findings of aspecific bowel activity using imuunoscintigraphy are in contrast with the results of former studies, while the existence of non-specific activity decreases the reliability of the method. Based on the literature and our experiences, we conclude that 99mTc HMPAO labelling should be the method of choice for the investigation of IBD patients.

Adult↗

Extraintestinal manifestations of inflammatory bowel disease.

Numerous extraintestinal diseases have been associated with IBD. The role of the gastrointestinal tract in host response to the foreign antigens present in the gut makes the enteric immune system highly susceptible to any external perturbation to the system. Dysregulation of the enteric immune response results in pathology in various organs outside of the gut. The site-specific manifestations of this immune response are not understood fully. Better understanding of the pathogenesis of IBD and the complex interactions between the gut immune system and the extraintestinal systems would provide insights into the development of many of these extraintestinal manifestations. Much is unknown about the presence of cardiac, pulmonary, and hematologic diseases in patients with IBD. True association or coincidental presence of the diseases in these organ systems with IBD requires better delineation. An important consideration in all patients with IBD presenting with extraintestinal manifestations should be a careful search for medication-related complications.

Eye Diseases↗

Inflammatory bowel disease in the elderly.

Approximately 15% of all patients with IBD first develop symptoms after age 65. As the number of elderly in the population continues to grow, clinicians should expect to see a greater number of elderly IBD patients. In general, the presenting features of IBD are similar to those encountered in younger patients, but the broad differential diagnosis of colitis in the elderly can make definitive diagnosis more challenging. Although most therapies for IBD have not been studied specifically in the elderly, as a general rule, medical and surgical treatment options are the same regardless of age. Osteoporosis, a condition generally associated with aging, should be managed aggressively in patients with IBD because many older persons already have a substantial baseline risk for accelerated bone loss.

Aged↗

Prevalence of the factor V Leiden mutation in human inflammatory bowel disease with different activity.

BACKGROUND: the developmental mechanism of inflammatory bowel disease (IBD) in patients is unknown, but it may be influenced by different environmental and genetical factors. AIMS of this study were: (1) to classify the IBD patients according the disease activity; and (2) to determine the presence of factor V Leiden mutation in IBD patients. PATIENTS AND METHODS: the observation was carried out in 49 patients with Crohn's disease (CD) and 29 patients with ulcerative colitis (UC). None of them had a history of thrombotic episodes. IBD was diagnosed by conventional clinical, endoscopic, radiological and histological criteria. The factor V Leiden mutation was detected by the polymerase chain reaction (PCR) method. Crohn's disease activity index (CDAI) was evaluated using the method of the National Cooperative Crohn's Disease Study. We determined the UC disease activity according to Truelove-Witts classification. RESULTS: The prevalence of factor V Leiden mutation was increased in both populations of the patients to compare it with healthy persons (14.28 and 27.58% vs. 5.26%, n=7/49 and 8/29 vs. 3/57). The statistical analysis did not show a significant relationship between the CDAI or the Truelove-Witts grade in UC and the presence of Leiden mutation. CONCLUSION: the presence of factor V Leiden mutation probably has a role in the development of IBD. Our results suggest a higher prevalence of this mutation in Central European patients than in Southern, Northern Europe or America, may be due to the genetical differences of these populations.

Adult↗

Course of gut inflammation in spondylarthropathies and therapeutic consequences.

Gut inflammation plays a crucial role in the pathogenesis of spondylarthropathies (SpA) since ileocolonoscopic studies have demonstrated the presence of gut inflammation in different forms of this concept: in ankylosing spondylitis (AS) (60%), in enterogenic (90%) and urogenital reactive arthritis (20%), in undifferentiated SpA (65%), in the pauciarticular and axial forms of psoriatic arthritis (16%), in late onset pauciarticular juvenile chronic arthritis (80%) and in acute anterior uveitis (66%). The strong relationship between gut and joint inflammation was demonstrated by performing a second ileocolonoscopy: remission of the joint inflammation was always connected with a disappearance of gut inflammation, whereas persistence of locomotor inflammation was mostly associated with the persistence of gut inflammation. During further evolution 20% of the non-ankylosing spondylitis SpA patients can develop AS. About 6% of the total group SpA patients, in whom inflammatory bowel disease (IBD) was excluded, developed Crohn's disease 5 to 9 years later. All these patients initially presented with gut inflammation, which indicates that this finding has prognostic value. The high prevalence of evolution to IBD in SpA patients confirms the thesis that both disease entities bear common pathogenic mechanisms, and confirms the place of IBD in the concept of SPA. Sulphasalazine (SASP), a successful drug in the treatment of IBD, has demonstrated its effectiveness in the treatment of SpA. The beneficial effect of the drug in this disease entity could be due to its anti-inflammatory effect on the gut wall, by normalizing its permeability and by preventing the entrance of antigens through the defective gut wall. However, SASP could not prevent the evolution to IBD.

Arthritis, Rheumatoid↗

Pregnancy, fertility, and disease course in patients with Crohn's disease and ulcerative colitis.

Pattern recognition of the long-term disease course before, during, and after pregnancy can provide us with data about the influence of pregnancy on IBD, and vice versa. Determinants that predict an indolent versus an aggressive disease course are currently being sought. Our intention is to analyze the disease course during pregnancy in an EU-IBD inception cohort of 1200 patients diagnosed from 1991 to 1993 and followed up for 10 years. We also attempt to evaluate such factors as smoking and medication and to predict pregnancy course and fertility in IBD as well as in a cross-sectional study of members of the patient organization EFCCA. One of the questions that arose was: what factor is responsible for the observation that pregnancy decreases the incidence of relapses and the development of fibrostenotic lesions? Relaxin and the glycoprotein YKL-40 are validated in the cohort. The protein relaxin, produced by the corpus luteum during pregnancy, increases the laxity of fibrous tissue. Collagen fibers are dissolved and disorganized. As maternal rejection of the fetus does not occur, a protein from the fetal lymphocytes most likely decreases the maternal lymphocyte response. Multiparity may lead to subtle, acquired immune deficits. Glycoprotein YKL-40, which causes fibrosis in RA and cirrhosis, is speculated to be lower in multiparous women than in nonpregnant women due to the fetal lymphocytes that secrete a protein that is a potential immune modulator. Knowledge gained from future EC-IBD studies may result in new legislation (e.g. regarding adoption) that can benefit IBD patients throughout Europe.

Journal Article↗

Changes in the incidence of inflammatory bowel disease: what does it mean?

A sharp rise in the incidence of inflammatory bowel disease (IBD) has been observed in the western world since the early 1950s. The increase in the incidence of ulcerative colitis preceded the increase in the incidence of Crohn's disease by about 10-15 years. In high-incidence areas, a female preponderance at a young age (20-40 years) is observed in Crohn's disease, whereas in ulcerative colitis male incidence is still high at older ages. IBD is more common in the developed world than in the developing world and, in both the United States and Europe, a north-south incidence gradient has been reported, with IBD more common in the north than in the south. There are also indications that, in typically low-incidence areas, more cases are being seen lately. At present, IBD is rather common in western Europe, affecting 0.5-1.0% of the population during their lifetime. It will be interesting to follow these temporal trends in the coming years, as they may teach us more about the role of environmental factors in the pathogenesis of IBD.

Journal Article↗

Genotype-phenotype relationship in inflammatory bowel disease.

Crohn's disease (CD) and ulcerative colitis (UC) are chronic diseases of unknown etiology. Much effort has been made in the last years to clarify the pathogenesis of inflammatory bowel disease (IBD). Data are not conclusive at the moment, but the most important known risk factor for developing IBD is a positive familial history. Genetic analyses have shown a linkage between loci on several chromosomes and IBD (IBD1 gene on chromosome 16 for CD and on chromosome 12 for UC). The association of genotype to specific phenotypes of disease could be hypothesized by the concordance of clinical characteristics in familial IBD, by the association of specific HLA haplotypes to clinically different groups of patients, and by different responses to treatment related to different polymorphisms of other chromosome 6 genes. The clinical heterogeneity of IBD has led to classifications of patients with Crohn's disease based upon clinical features (e.g. Rome and Vienna classifications) that allow the identification of subgroups of patients with similar clinical behavior. The possible drawbacks of these classifications are the lack of validation of intra-interobserver concordance, the absence of prospective evaluations, and stratification into too many subgroups. Furthermore, in our experience, clinical presentation (surgical or medical) seems to have a good correlation with prognosis, is easy identifiable, and can be applied at the time of diagnosis. In UC, extension of disease and clinical behavior correlate with prognosis. For these reasons, studies correlating genotype to phenotype should be performed to improve our knowledge of the diseases and possibly to stratify patients into different subgroups for more personalized treatments, in clinical trials and for research purposes.

Journal Article↗

Nonsteroidal anti-inflammatory drugs and inflammatory bowel disease: current perspectives.

Mechanisms underlying the gastric toxicity of nonsteroidal anti-inflammatory drugs (NSAIDs) have been extensively investigated, whereas those leading to intestinal damage are not completely understood. Several hypotheses have been put forward on the pathophysiology of intestinal damage by NSAIDs: enhanced intestinal permeability, inhibition of cyclooxygenase (COX), enterohepatic recirculation, and formation of adducts. The effects of COX-2 selective inhibitors, which appear to have better gastric tolerability when compared to nonselective NSAIDs, on normal and inflamed intestinal mucosa (as in Crohn's disease or ulcerative colitis) are still largely unexplored. If COX-2 inhibition plays a key role in suppressing the inflammatory process, recent evidence suggests that COX-2 products are involved in maintaining the integrity of intestinal mucosa, in the healing of gastrointestinal ulcers and in the modulation of inflammatory bowel disease (IBD). Animal models of intestinal inflammation have so far yielded conflicting results on the effects of COX-2 selective inhibitors on the intestinal mucosa. It is now clear that NSAIDs do not act through cyclooxygenase inhibition, but also have different targets such as nuclear factor-kappaB and/or peroxisome proliferator-activated receptors gamma. The peculiar pharmacological profile of each compound may help to explain the different impact of each NSAID on the inflammatory process and on IBD. Notably, the salicylic acid derivative 5-ASA is widely used in the treatment of IBD and is believed to act through nuclear factor-kappaB inhibition. Although the use of COX-2 selective inhibitors remains contraindicated in patients with IBD, studying their effects on intestinal mucosa may offer new insights into their subcellulars mechanisms of action and open new avenues for the development of novel therapies for IBD.

Animals↗

Pancreatic and biliary tract disorders in inflammatory bowel disease.

Hepatobiliary disorders occur frequently in patients with IBD, with PSC and cholangiocarcinoma being the most clinically significant for endoscopists. Endoscopic therapy for PSC is effective in improving symptoms, biochemical parameters, and radiographic abnormalities. Endoscopic therapy may also confer survival benefit, but this has yet to be confirmed in randomized, controlled trials. Treatment should be restricted to those individuals with a rapid decline in liver function testing or those with recurrent cholangitis. Cholangiocarcinoma is a serious complication of PSC and carries an extremely poor prognosis. ERCP with brush cytology has a relatively low sensitivity and the diagnosis is usually made after the disease has become metastatic. Malignant biliary obstruction can be palliated by endoscopic stenting. Photodynamic therapy is a promising experimental technique that may confer symptomatic and survival benefit in patients with nonresectable, advanced cholangiocarcinoma. IBD patients also have an elevated risk for developing acute and chronic pancreatitis as well as pancreatic insufficiency. The majority of cases of acute pancreatitis are likely due to medication side effects and local structural complications of IBD. The remainder may possibly represent true extraintestinal manifestations of IBD. Chronic pancreatitis is frequently subclinical, but may be accompanied by clinically relevant exocrine insufficiency. ERCP is the test of choice for the diagnosis of chronic pancreatitis, but the role of endoscopy in the therapeutic management of IBD-associated chronic pancreatitis remains to be defined.

Bile Duct Neoplasms↗

Inflammatory bowel disease.

Inflammatory bowel disease (IBD) comprises a group of idiopathic diseases of the intestine characterized by chronic inflammation of the bowel with periods of exacerbation and remission. The 2 major categories of IBD are ulcerative colitis and Crohn's disease, and each disease is distinct both clinically and histologically. The exact cause of IBD remains unknown, but several theories have been proposed. Primary care physicians are frequently confronted with the initial diagnosis and management of patients with IBD, and medical treatment options have rapidly expanded in recent years. This article reviews the epidemiology and pathogenesis of IBD; its clinical presentations and complications, which are essential to understanding this complex disease; and the available treatment options.

Colitis, Ulcerative↗

Connective tissue growth factor: a novel regulator of mucosal repair and fibrosis in inflammatory bowel disease?

Inflammatory bowel disease (IBD) is a multifactorial disorder which is characterized by massive damage of the epithelium and the underlying mesenchyme of the intestine. Due to the potent effect of connective tissue growth factor (CTGF) on fibroblast proliferation and connective tissue deposition we speculated about a possible role of this mitogen in IBD. Here we demonstrate a strikingly increased expression of CTGF mRNA in surgical specimens of patients suffering from two forms of IBD, Crohn's disease and ulcerative colitis. In most specimens, the levels of CTGF mRNA correlated with the degree of inflammation as assessed by histological analysis of adjacent tissue samples and by expression analysis of the pro-inflammatory cytokine interleukin-1 beta. However, areas of little inflammation which were characterized by severe fibrosis also revealed high levels of CTGF mRNA. Expression of transforming growth factor beta-1 (TGF-beta 1), the only known inducer of CTGF so far, as well as of the CTGF target genes collagen I alpha 1, fibronectin and integrin alpha 5 revealed a strong correlation with the expression of CTGF. These data suggest a prominent role of CTGF in the repair of mucosal injury in IBD and in the aberrant deposition of extracellular matrix leading to fibrosis and stenosis, one major complication in IBD, especially in Crohn's disease.

Animals↗

Initial experience with wireless capsule enteroscopy in the diagnosis and management of inflammatory bowel disease.

BACKGROUND AND AIMS: Wireless capsule enteroscopy (WCE) offers the potential to directly visualize the entire small bowel and identify superficial lesions not detected by traditional endoscopy and radiography. The aim of this study is to assess the clinical utility of WCE in the evaluation of patients with known or suspected inflammatory bowel disease (IBD). METHODS: Fifty patients with ongoing symptoms underwent Given M2A endoscopic capsule examinations. Indications included: (1) evaluation for small-bowel involvement in patients with IBD with isolated colitis (n = 22), (2) determination of the extent of small-bowel disease in patients with Crohn's disease (CD; n = 20), and (3) workup of suspected IBD (n = 8). Outcome measures were classified as diagnostic when multiple ulcerations were present, suspicious when </=3 ulcerations were seen, and nonspecific or normal. RESULTS: WCE findings were diagnostic for CD in 20 patients and suspicious for small-bowel CD in 10 patients. Seventeen of 20 patients with diagnostic WCE findings improved with increased IBD-directed medical therapy, as did 7 of 10 patients with suspicious study results. WCE was normal or showed nonspecific findings in the remaining 20 patients. Notably, identification of small-bowel lesions in 5 patients with a previous history of isolated colitis resulted in a change in diagnosis to CD after confirmatory ileoscopy with biopsy. CONCLUSIONS: Results of this preliminary study suggest that WCE is a novel and potentially clinically useful method of directly visualizing and diagnosing small-bowel lesions in patients with IBD that can be missed by traditional endoscopic and radiological procedures.

Adolescent↗

Concerns of patients with inflammatory bowel disease: a review of emerging themes.

Idiopathic, chronic inflammatory bowel disease (IBD) refers to two diseases-ulcerative colitis (UC) and Crohn's disease (CD). Despite an abundant literature discussing the pathophysiology and treatment of these diseases, little if any empirical studies have focused on patients' subjective experiences with their diseases. The purpose of this paper was to identify and discuss the concerns of individuals with IBD and to suggest that the integration of concerns in clinical management is necessary for a comprehensive understanding of these chronic and debilitating diseases. In addition, case studies were included to highlight the concerns of people with IBD. Our review of the literature identified eight categories of concerns for individuals with IBD. They included loss of energy, loss of control, body image, isolation and fear, not reaching full potential, feeling dirty, and lack of information from the medical community. In conclusion, we argue that the efficacy of treatment for IBD would be greatly improved if psychosocial issues were to be integrated into treatment protocols.

Adaptation, Psychological↗

Self-care agency and quality of life among adults diagnosed with inflammatory bowel disease.

Individuals with inflammatory bowel disease (IBD) often exhibit anxiety and depression, pain and reduced energy but may not adequately develop self-care agency (SCA) to manage IBD. The purpose of this study was to examine whether SCA is related to quality of life in adults diagnosed with IBD. The sample of 34 individuals for this descriptive, correlational study completed three questionnaires including the Appraisal of self-care agency scale (A.S.A.-A Scale), the Inflammatory bowel disease questionnaire and a Demographic data questionnaire. Results indicated SCA was unrelated to indicators of quality of life among IBD individuals. This finding may be attributed to the high level of functioning of the sample. However, IBD quality of life (emotional functioning, social functioning, and bowel and systemic symptoms) was negatively correlated with the number of medications individuals took and positively correlated with the number of diagnosed chronic illnesses.

Adult↗

Synergistic effect of immunoregulatory cytokines on peripheral blood monocytes from patients with inflammatory bowel disease.

Active inflammatory bowel disease (IBD) is characterized by increased monocyte secretion of proinflammatory cytokines. Immunoregulatory cytokines such as Interleukin (IL)-4, IL-10, and IL-13 are capable of inhibiting the proinflammatory cytokine response of activated monocytes. The aim of our study was to determine the effect of different antiinflammatory cytokines under various culture conditions and to evaluate combinations of antiinflammatory cytokines in down-regulating monocyte response in IBD. Peripheral monocytes from patients with active IBD were isolated and stimulated with pokeweed mitogen (PWM). IL-4, IL-10, IL-13 and a combination of IL-4/IL-10 and IL-10/IL-13 were added at different concentrations and different times. Secretion of IL-1beta and TNF-alpha was assessed using sandwich ELISA systems. There was a diminished down-regulation of TNF-alpha by IL-4 and IL-13 in IBD when the cytokines were added at the time of stimulation, while there was a significantly higher down-regulation when monocytes were primed with these Th-2 cytokines 24 hr before activation. IL-10 plus IL-4 and IL-10 plus IL-13, respectively, inhibited the proinflammatory cytokine response of monocytes as well as matured macrophages much more than IL-4, IL-10, or IL-13 alone. Even at suboptimal concentrations for each cytokine alone, a combination of cytokines showed synergistic inhibitory effects. In summary, a combination of antiinflammatory cytokines is more effective in down-regulating the response of activated monocytes than using the cytokines alone and thus may have a potential therapeutic benefit for patients with IBD.

Cells, Cultured↗

Peripheral blood lymphocyte beta 2 integrin and ICAM expression in inflammatory bowel disease.

The beta 2 integrin intercellular adhesion molecule (ICAM) adhesion pathway is likely pivotal in the immunopathogenesis of inflammatory bowel disease (IBD). We have undertaken a comprehensive study of peripheral blood lymphocyte (PBL) expression of all beta 2 integrins and ICAMs in patients with IBD using flow cytometry and assessed our data on the basis of IBD diagnosis, disease state of activity, and use of corticosteroids. Blood was collected from patients with Crohn's disease (N = 49), ulcerative colitis (N = 43), and normal control volunteers (N = 15). Mononuclear cells were separated using a Ficoll-Hypaque gradient and prepared for flow cytometry. The data were analyzed for percentage expression, mean fluorescent intensity (MFI) as well as for histogram patterns. The analysis was stratified for disease diagnosis, disease activity level, and for use of prednisone among patients with active disease. There was decreased percentage expression of CD11a, CD18, and ICAM-3 in Crohn's disease and ulcerative colitis compared with normal, but an increased MFI for these molecules among patients with Crohn's disease. Active Crohn's disease showed a greater change in this pattern compared with both inactive disease and active ulcerative colitis. CD11a and CD18 histograms typically had two peaks of expression. The predominance of one peak over the other varied with disease diagnosis and activity. CD11b and alpha d expression patterns were not different in IBD compared with normal. CD11c was not expressed by PBLs and, ICAM-2, typically an endothelial ligand, was expressed on PBLs. There were changes in the expression of beta 2 integrins in IBD, which were more evident in Crohn's disease than ulcerative colitis. We hypothesize that the decreased percentage expression and increased MFI of CD11a, CD18, and ICAM-3 may suggest that cells up-regulate these ligands following activation and are egressing into tissue.

Adult↗