Risk factors for osteoporosis in inflammatory bowel disease patients

Inflammatory bowel disease (IBD) patients exhibit higher risk for bone loss than the general population. The chronic inflammation causes a reduction in bone mineral density (BMD), which leads to osteopenia and osteoporosis. This article reviewed each risk factor for osteoporosis in IBD patients. Inflammation is one of the factors that contribute to osteoporosis in IBD patients, and the main system that is involved in bone loss is likely RANK/RANKL/osteoprotegerin. Smoking is a risk factor for bone loss and fractures, and many mechanisms have been proposed to explain this loss. Body composition also interferes in bone metabolism and increasing muscle mass may positively affect BMD. IBD patients frequently use corticosteroids, which stimulates osteoclastogenesis. IBD patients are also associated with vitamin D deficiency, which contributes to bone loss. However, infliximab therapy is associated with improvements in bone metabolism, but it is not clear whether the effects are because of inflammation improvement or infliximab use. Ulcerative colitis patients with proctocolectomy and ileal pouches and Crohn’s disease patients with ostomy are also at risk for bone loss, and these patients should be closely monitored.     

Smoking, physical activity, nutrition and lifestyle: environmental factors and their impact on IBD

Current smoking increases the risk of developing Crohn's disease and worsens its course, increasing the need for steroids, immunosuppressants, and re-operations. On the contrary, smoking protects against ulcerative colitis and after disease onset improves its course, decreasing the need for colectomy. Smoking cessation improves Crohn's disease and worsens ulcerative colitis. Achieving smoking cessation in Crohn's disease is thus an important goal of therapy, whereas patients with ulcerative colitis should not be discouraged to quit, because the beneficial effect of smoking for their disease is counterbalanced by the deleterious respiratory and cardiovascular effects of tobacco. Physical activity improves quality of life without detrimental effect on disease activity, and may contribute to increase muscle mass and to prevent osteoporosis. Regarding nutrition, a Western diet may be associated with an increased risk of IBD, and a case-control study revealed an increased consumption of linoleic acid before diagnosis of ulcerative colitis. Liquid diets may improve Crohn's disease flares and decrease the need for steroids; however, there are no defined diets able to improve the disease course, and in Crohn's disease, supplementation with omega-3 fatty acids did not show a significant benefit. Obesity is becoming more prevalent in IBD and may be associated with higher disease activity. In total, adhering to four simple lifestyle factors - never smoking, physical activity, prudent diet and body mass index <25 - may have a strong impact both on the prevention of major chronic diseases and on the course of IBD.     

Nutritional management of inflammatory bowel disease; an overview of the evidences

Background and aimsInflammatory bowel disease (IBD) is a chronic relapsing–remitting systemic disease and one of the most common gastrointestinal diseases that affect many people. This review designed to report the latest findings on the association between some nutrients and IBD.MethodsA review was performed to summarize the effect of various aspects of nutrition and diet on clinical course, the severity of disease, intestinal epithelial inflammation, inflammatory and oxidative stress markers. Literature searches were conducted in PubMed and Google Scholar up to June 27, 2021.ResultsVarious studies have shown that an unhealthy diet and deficiency of some nutrients are involved in the etiology of IBD. It has also been shown that intestinal dysbiosis can increase the risk of developing IBD. The results of some studies have shown that supplementation with some nutrients such as omega-3 polyunsaturated fatty acids and vitamin D and probiotics may have beneficial results in patients with IBD. Adherence to some restrictive diets has also been helpful in some studies.ConclusionsFollowing proper nutritional approaches can play an essential role in managing IBD symptoms. Further studies are needed to substantiate some of these findings.     

Unique dietary-related mouse model of colitis

BACKGROUND: A high-fat diet is a risk factor for the development of inflammatory bowel disease (IBD) in humans. Deoxycholate (DOC) is increased in the colonic contents in response to a high-fat diet. Thus, an elevated level of DOC in the colonic lumen may play a role in the natural course of development of IBD. METHODS: Wild-type B6.129 mice were fed an AIN-93G diet, either supplemented with 0.2% DOC or unsupplemented and sacrificed at 1 week, 1 month, 3 months, 4 months, and 8 months. Colon samples were assessed by histopathological, immunohistochemical, and cDNA microarray analyses. RESULTS: Mice fed the DOC-supplemented diet developed focal areas of colonic inflammation associated with increases in angiogenesis, nitrosative stress, DNA/RNA damage, and proliferation. Genes that play a central role in inflammation and angiogenesis and other related processes such as epithelial barrier function, oxidative stress, apoptosis, cell proliferation/cell cycle/DNA repair, membrane transport, and the ubiquitin-proteasome pathway showed altered expression in the DOC-fed mice compared with the control mice. Changes in expression of individual genes (increases or reductions) correlated over time. These changes were greatest 1 month after the start of DOC feeding. CONCLUSIONS: The results suggest that exposure of the colonic mucosa to DOC may be a key etiologic factor in IBD. The DOC-fed mouse model may reflect the natural course of development of colitis/IBD in humans, and thus may be useful for determining new preventive strategies and lifestyle changes in affected individuals.     

Influence of environmental factors in the development of inflammatory bowel diseases

Idiopathic inflammatory bowel diseases(IBD), Crohn's disease(CD) and ulcerative colitis(UC), are multifactorial diseases that are manifested after disruption of a genetic predisposed individual and its intestinal microflora through an environmental stimulus. Urbanization and industrialization are associated with IBD. Epidemiological data, clinical observations and family/immigrants studies indicate the significance of environmental influence in the development of IBD. Some environmental factors have a different effect on the subtypes of IBD. Smoking and appendectomy is negatively associated with UC, but they are aggravating factors for CD. A westernized high fat diet, full of refined carbohydrates is strongly associated with the development of IBD, contrary to a high in fruit, vegetables and polyunsaturated fatty acid-3 diet that is protective against these diseases. High intake of nonsteroidal antiinflammatory drug and oral contraceptive pills as well as the inadequacy of vitamin D leads to an increased risk for IBD and a more malignant course of disease. Moreover, other factors such as air pollution, psychological factors, sleep disturbances and exercise influence the development and the course of IBD. Epigenetic mechanism like DNA methylation, histone modification and altered expression of miR NAS could explain the connection between genes and environmental factors in triggering the development of IBD.     

Prevalence of hyperhomocysteinaemia, activated protein C resistance and prothrombin gene mutation in inflammatory bowel disease

BACKGROUND: Thromboembolic disease is a significant cause of morbidity and mortality in patients with inflammatory bowel disease (IBD). A hypercoagulable state exists in IBD that may involve many components of haemostasis and is closely linked to the disease pathogenesis. It has been proposed that microvascular thrombosis and infarction may trigger the underlying inflammatory process. AIM: To determine the prevalence of prothrombotic factors including hyperhomocysteinaemia, activated protein C (APC) resistance and prothrombin gene mutations as well as vitamin levels in the local IBD population. METHOD: A total of 68 patients (37 men and 31 women) attending the IBD clinic were enrolled into the study. Citrated and ethylenediamine tetraacetic acid blood samples were collected from all patients as well as from 30 controls. Homocysteine levels were measured using the IMX immunoassay. APC resistance was measured using an unmodified activated partial thromboplastin time-based clotting assay. Prothrombin mutations were determined using polymerase chain reaction with the HB-gene factor II detection system. RESULTS: Mean homocysteine levels were significantly higher and APC resistance ratios significantly lower in IBD patients compared with controls. No significant difference was detected between patients with ulcerative colitis or Crohn's disease. There was no significant increase in the incidence of prothrombin mutation in IBD patients. IBD patients had lower vitamin B12 and higher serum folate levels than controls. CONCLUSION: High homocysteine and high serum folate may be associated with low vitamin B12 levels in IBD patients. We did not find any association between a low APC ratio and the factor V Leiden mutation or high factor VIII levels. Both hyperhomocysteinaemia and a low APC ratio may contribute to an increased risk of thromboembolic disease in IBD patients.     

Impact of environmental and dietary factors on the course of inflammatory bowel disease

Besides their possible effects on the development of inflammatory bowel disease (IBD), some environmental factors can modulate the clinical course of both ulcerative colitis (UC) and Crohn's disease (CD). This review is mainly devoted to describing the current knowledge of the impact of some of these factors on the outcome of IBD, with special emphasis on smoking and diet. Although the impact of smoking on the susceptibility to develop CD and UC is firmly established, its influence on the clinical course of both diseases is still debatable. In CD, active smoking is a risk factor for postoperative recurrence. Beyond this clinical setting, smoking cessation seems to be advantageous in those CD patients who were smokers at disease diagnosis, while smoking resumption may be of benefit in ex-smokers with resistant UC. The role of dietary habits on the development of IBD is far from being well established. Also, food intolerances are very frequent, but usually inconsistent among IBD patients, and therefore no general dietary recommendations can be made in these patients. In general, IBD patients should eat a diet as varied as possible. Regarding the possible therapeutic role of some dietary components in IBD, lessons should be drawn from the investigation of the primary therapeutic effect of enteral nutrition in CD. Low-fat diets seem to be particularly useful. Also, some lipid sources, such as olive oil, medium-chain triglycerides, and perhaps omega-3 fatty acids, might have a therapeutic effect. Fermentable fiber may have a role in preventing relapses in inactive UC.     

Pre-illness dietary factors in inflammatory bowel disease.

BACKGROUND: The effect of environmental factors has been demonstrated in the pathogenesis of inflammatory bowel disease (IBD). Nutrition may be one of them. AIM: To investigate the pre-illness diet in patients with recent IBD in comparison with matched population and clinic controls. METHODS: Quantified dietary histories were obtained from 87 patients with recent IBD (54 ulcerative colitis (UC) and 33 Crohn's disease (CD)) and 144 controls. Odds ratios (OR) for IBD were derived for intake levels of various foods. RESULTS: A high sucrose consumption was associated with an increased risk for IBD (OR 2.85 (p = 0.03) against population controls and 5.3 (p = 0.00) against clinic controls). Lactose consumption showed no effect while fructose intake was negatively associated with risk for IBD (NS). Similar trends were noted in UC and CD. A high fat intake was associated with an increased risk for UC; this was particularly marked for animal fat (OR 4.09, p = 0.02) and cholesterol (OR 4.57, p = 0.02). A high intake of fluids (p = 0.04), magnesium (p = 0.04), vitamin C, and fruits (NS) was negatively associated with the risk for IBD, while a positive association was found for retinol (p = 0.01). Most of the findings were similar in UC and CD except for potassium and vegetable consumption which showed a negative association only with risk for CD. CONCLUSIONS: An association was found between pre-illness diet and subsequent development of UC and CD. The effect of dietary components may be primary or modulatory.     

Clinical management of inflammatory bowel disease in the organ recipient

There was estimated a higher incidence of de novo inflammatory bowel disease(IBD)after solid organ transplantation than in the general population.The onset of IBD in the organ transplant recipient population is an important clinical situation which is associated to higher morbidity and difficulty in the medical therapeutic management because of possible interaction between anti-reject therapy and IBD therapy.IBD course after liver transplantation(LT)is variable,but about one third of patients may worsen,needing an increase in medical therapy or a colectomy.Active IBD at the time of LT,discontinuation of 5-aminosalicylic acid or azathioprine at the time of LT and use of tacrolimusbased immunosuppression may be associated with an unfavorable outcome of IBD after LT.Anti-tumor necrosis factor alpha(TNFα)therapy for refractory IBD may be an effective and safe therapeutic option after LT.The little experience of the use of biological therapy in transplanted patients,with concomitant anti-rejection therapy,suggests there be a higher more careful surveillance regarding the risk of infectious diseases,autoimmune diseases,and neoplasms.An increased risk of colorectal cancer(CRC)is present also after LT in IBD patients with primary sclerosing cholangitis(PSC).Anannual program of endoscopic surveillance with serial biopsies for CRC is recommended.A prophylactic colectomy in selected IBD/PSC patients with CRC risk factors could be a good management strategy in the CRC prevention,but it is used infrequently in the majority of LT centers.About 30%of patients develop multiple IBD recurrence and 20%of patients require a colectomy after renal transplantation.Like in the liver transplantation,anti-TNFαtherapy could be an effective treatment in IBD patients with conventional refractory therapy after renal or heart transplantation.A large number of patients are needed to confirm the preliminary observations.Regarding the higher clinical complexity of this subgroup of IBD patients,a close multidisciplinary approach between an IBD dedicated gastroenterologist and surgeon and an organ transplantation specialist is necessary in order to have the best clinical management of IBD after transplantation.     

Environmental risk factors in Crohn's disease and ulcerative colitis (excluding tobacco and appendicectomy)

A rapid increase in the incidence of Crohn's disease and ulcerative colitis in developed countries, the occurrence of Crohn's disease in spouses, and a lack of complete concordance in monozygotic twins are strong arguments for the role of environmental factors in inflammatory bowel disease (IBD). Research in the field of environmental factors in IBD is based upon epidemiological (geographical and case-control), clinical and experimental studies. The role of two environmental factors has clearly been established in IBD. Smoking is a risk factor for Crohn's disease and a protective factor for ulcerative colitis; appendectomy is a protective factor for ulcerative colitis. Many other environmental factors for IBD have been investigated, including infectious agents, diet, drugs, stress and social status. They are detailed in the present review. Among them, atypical Mycobacteria, oral contraceptives and antibiotics could play a role in Crohn's disease. To date, three hypotheses associate environmental factors with the pathophysiology of IBD (loss of tolerance of intestinal immune system towards commensal bacterial flora): the hygiene, infection and cold chain hypotheses. Much work remains to be done to identify risk factors for IBD. Research identifying environmental factors that might cause a predisposition to IBD is useful. It may lead to disease prevention in subjects who are genetically predisposed and disease improvement in patients.     

Diet therapy for inflammatory bowel diseases: The established and the new

Although patients with inflammatory bowel diseases(IBD) have a strong interest in dietary modifications as part of their therapeutic management, dietary advice plays only a minor part in published guidelines. The scientific literature shows that dietary factors might influence the risk of developing IBD, that dysbiosis induced by nutrition contributes to the pathogenesis of IBD, and that diet may serve as a symptomatic treatment for irritable bowel syndrome-like symptoms in IBD. The role of nutrition in IBD is underscored by the effect of various dietary therapies. In paediatric patients with Crohn’s disease(CD) enteral nutrition(EN) reaches remission rates similar to steroids. In adult patients, however, EN is inferior to corticosteroids. EN is not effective in ulcerative colitis(UC). Total parenteral nutrition in IBD is not superior to steroids or EN. The use of specific probiotics in patients with IBD can be recommended only in special clinical situations. There is no evidence for efficacy of probiotics in CD. By contrast, studies in UC have shown a beneficial effect in selected patients. For patients with pouchitis, antibiotic treatment followed by probiotics, like VSL#3 or Lactobacillus GG, is effective. When probiotics are used, the risk of bacterial translocation and subsequent bacteremia has to be considered. More understanding of the normal intestinal microflora, and better characterization of probiotic strains at the phenotypic and genomic levels is needed as well as clarification of the mechanisms of action in different clinical settings. A FODMAP reduced diet may improve symptoms in IBD.     

Hyperhomocysteinemia as a potential contributor of colorectal cancer development in inflammatory bowel diseases: A review

Homocysteine is an amino acid generated metabolically by the S-adenosylmethionine-dependent transmethylation pathway. In addition to being a well-known independent risk factor for coronary heart disease, is also a risk factor for cancer. Patients suffering from inflammatory bowel diseases(IBD) including ulcerative colitis and Crohn’s disease are at increased risk of developing colorectal cancer in comparison to healthy individuals. Furthermore, the risk of hyperhomocysteinaemia is significantly higher in IBD patients when compared with controls. In the present article, we review the mechanisms in which hyperhomocysteinemia may contribute to increased risk of colorectal cancer in IBD patients.     

Inflammatory bowel disease and thromboembolism

Patients with inflammatory bowel disease (IBD) have an increased risk of vascular complications. Thromboembolic complications, both venous and arterial, are serious extraintestinal manifestations complicating the course of IBD and can lead to significant morbidity and mortality. Patients with IBD are more prone to thromboembolic complications and IBD per se is a risk factor for thromboembolic disease. Data suggest that thrombosis is a specific feature of IBD that can be involved in both the occurrence of thromboembolic events and the pathogenesis of the disease. The exact etiology for this special association between IBD and thromboembolism is as yet unknown, but it is thought that multiple acquired and inherited factors are interacting and producing the increased tendency for thrombosis in the local intestinal microvasculature, as well as in the systemic circulation. Clinicians’ awareness of the risks, and their ability to promptly diagnose and manage tromboembolic complications are of vital importance. In this review we discuss how thromboembolic disease is related to IBD, specifically focusing on: (1) the epidemiology and clinical features of thromboembolic complications in IBD; (2) the pathophysiology of thrombosis in IBD; and (3) strategies for the prevention and management of thromboembolic complications in IBD patients.     

Low vitamin B(6) plasma levels,a risk factor for thrombosis,in inflammatory bowel disease: role of inflammation and correlation with acute phase reactants

OBJECTIVES: Individuals with inflammatory bowel disease (IBD) are at increased risk for thrombosis and vitamin deficiencies. Low plasma levels of vitamin B(6) are an independent risk factor for thrombosis and may cause hyperhomocysteinemia, another recognized risk factor for thrombosis. The aim of this study was to evaluate vitamin B(6) plasma levels in IBD patients. METHODS: We studied 61 IBD patients: 32 with Crohn's disease and 29 with ulcerative colitis. For each patient, three sex- and age-matched healthy control subjects were studied. RESULTS: Median vitamin B(6) levels were significantly lower in IBD patients (22.0 pmol/L, range 3.6-231.0) than in controls (31.1 pmol/L, 3.7-363.4; p < 0.01). In all, 13.1% IBD patients and 5.5% controls had plasma vitamin B(6) levels lower than the 5th percentile of distribution in normal controls (p < 0.05). Low vitamin B(6) levels were significantly more frequent in patients with active disease than in patients with quiescent disease (seven of 26, 26.9%, vs one of 35, 2.9%; p < 0.001). Moreover, patients with active disease had significantly lower median vitamin B(6) levels (13.4 pmol/L, range 3.6-124.0) than patients in a quiescent phase (27.0 pmol/L, 7.8-231.0; p < 0.001). Low vitamin B(6) levels were significantly correlated with serum concentrations of C-reactive protein (r = -0.36, 95% CI = -0.59 to -0.09, p < 0.01) and alpha(1)-acid-glycoprotein (r = -0.37, 95% CI = -0.59 to -0.10, p < 0.01). Hyperhomocysteinemia was more frequent in patients with low vitamin B(6) levels (three of eight, 37.5%) than in patients with normal levels (nine of 53, 17.0%; p = 0.18). There was no statistically significant correlation between vitamin B(6) and homocysteine plasma levels (r = -0.13, 95% CI = -0.37 to +0.14, p = 0.33). CONCLUSIONS: Low vitamin B(6) plasma levels, an independent risk factor for thrombosis, are frequent in patients with IBD, especially those with active disease.     

Inflammatory bowel disease and the risk for cardiovascular disease: Does all inflammation lead to heart disease?

Inflammation has a strong role in the development of atherosclerotic cardiovascular disease (ASCVD). Several systemic inflammatory conditions have been linked to an increased risk of ASCVD; however, this has not been well established in Inflammatory Bowel Disease (IBD). IBD is comprised of Ulcerative Colitis and Crohn's disease, both of which involve chronic inflammation of the intestinal tract, often with evidence of systemic involvement. Several ASCVD risk factors such as smoking, diabetes, poor diet and the presence of obesity may increase the risk of ASCVD in patients suffering from IBD, despite a lower prevalence of hypertension and hypercholesterolemia. Medications used to treat IBD and target inflammation, such as steroids, may also accelerate the risk of the risk for ASCVD heart failure while exacerbating ASCVD risk factors. Several studies have demonstrated an elevated risk of acute myocardial infarction and stroke in these patients, most notably in women and in younger patients. Some cohort studies have also suggested a link between IBD and both atrial fibrillation and heart failure, particularly during periods of active flares. All IBD patients, particularly younger individuals, should be screened for ASCVD risk factors with aggressive risk factor modification to reduce the risk of cardiovascular events. Further research is needed to identify how to prevent and treat cardiovascular events that occur in patients with IBD, particularly during active flares.     

Reduced plasma antioxidant concentrations and increased oxidative DNA damage in inflammatory bowel disease.

BACKGROUND: Oxidative stress is believed to play a key role in the pathogenesis of inflammatory bowel disease (IBD)-related intestinal damage. Circulating antioxidants may have a role to play in preventing free radical-mediated tissue injury. METHODS: Plasma vitamin A, E and carotenoid concentrations, leukocytic genomic damage and 8-hydroxy-deoxy-guanosine (8-OHdG) concentration were determined in 46 ulcerative colitis (UC) patients, 37 Crohn disease (CD) patients and 386 controls. A 20 ml blood sample was taken from each subject for antioxidant and 8-OHdG measurements. A food frequency questionnaire was administered to a sample of subjects from each group to evaluate daily intake of dietary compounds. RESULTS: Antioxidant concentration was significantly reduced in IBD patients, particularly in those with active disease, with respect to controls (P < 0.0001). 8-OHdG concentrations were significantly increased in IBD patients compared to controls, independent of disease activity (P < 0.05). No correlation was found between antioxidant and 8-OHdG concentrations. Carotenoid concentrations were significantly reduced in malnourished IBD patients (0.89 +/- 0.14 micromol/l) compared to patients with normal or high body mass index (1.83 +/- 0.12 micromol/l; P < 0.05), independent of disease activity or extension. Protein, fruit and vegetable intakes of IBD patients were significantly lower than those of controls. CONCLUSIONS: Depletion of antioxidants is likely to be important in the pathophysiology of IBD: UC and CD patients show increased free radical peripheral leukocyte DNA damage and decreased plasma antioxidant defenses. These results indicate the necessity of further studies to establish whether optimal vitamin status may improve the clinical course of UC and CD.     

Crucial steps in the natural history of inflammatory bowel disease

Inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), are chronic, progressive and disabling disorders. Over the last few decades, new therapeutic approaches have been introduced which have led not only to a reduction in the mortality rate but also offered the possibility of a favorable modification in the natural history of IBD. The identification of clinical, genetic and serological prognostic factors has permitted a better stratification of the disease, thus allowing the opportunity to indicate the most appropriate therapy. Early treatment with immunosuppressive drugs and biologics has offered the opportunity to change, at least in the short term, the course of the disease by reducing, in a subset of patients with IBD, hospitalization and the need for surgery. In this review, the crucial steps in the natural history of both UC and CD will be discussed, as well as the factors that may change their clinical course. The methodological requirements for high quality studies on the course and prognosis of IBD, the true impact of environmental and dietary factors on the clinical course of IBD, the clinical, serological and genetic predictors of the IBD course (in particular, which of these are relevant and appropriate for use in clinical practice), the impact of the various forms of medical treatment on the IBD complication rate, the role of surgery for IBD in the biologic era, the true magnitude of risk of colorectal cancer associated with IBD, as well as the mortality rate related to IBD will be stressed; all topics that are extensively discussed in separate reviews included in this issue of World Journal of Gastroenterology.     

Clinical factors are associated with vitamin D levels in IBD patients: A retrospective analysis

OBJECTIVE

There is growing evidence that vitamin D deficiency plays a role in the development and the course of inflammatory bowel disease (IBD). However, the correlation between vitamin D deficiency and clinical parameters in IBD is still not completely understood.

METHODS

A retrospective study of IBD patients was performed. Vitamin D values were analyzed, regardless of vitamin D substitution administration, and correlated with clinical parameters such as medical therapy, anatomical situation, location of the disease and disease activity. Level of 25‐hydroxyvitamin D [25(OH)D] <50 nmoL/L was regarded as vitamin D deficiency and <75 nmoL/L as insufficiency.

RESULTS

In total, 208 IBD patients were analyzed, including 123 with Crohn's disease (CD) and 85 with ulcerative colitis (UC). Therapy with azathioprine did not affect the vitamin D values of either disease entity. But CD patients benefited from therapy with tumor necrosis factor‐α inhibitor and exhibited significantly higher vitamin D levels than those without. Furthermore, significantly lower vitamin D levels were found if CD was located in the small bowel or if the small bowel had been resected. Moreover, significantly lower levels of vitamin D were detectable for high disease activity (reflected by high simple clinical colitis activity index values) in patients with UC.

CONCLUSIONS

Vitamin D deficiency is common in patients with IBD. However, certain clinical situations lead to significantly lower vitamin D levels and may therefore require close monitoring for vitamin D deficiency.     

Inflammatory bowel disease:Epidemiology,pathology and risk factors for hypercoagulability

Hypercoagulability observed in patients with inflammatory bowel diseases(IBD)may lead to thromboembolic events(TE),which affect the venous and arterial systems alike and are an important factor in patients’morbidity and mortality.The risk of TE in IBD patients has been demonstrated to be approximately threefold higher as compared to the general population.The pathogenesis of thrombosis in IBD patients is multifactorial and not fully explained.The most commonly listed factors include genetic and immune abnormalities,disequilibrium between procoagulant and anticoagulant factors,although recently,the role of endothelial damage as an IBD-triggering factor is underlined.Several studies report that the levels of some coagulation enzymes,including fibrinogen,factorsⅤ,Ⅶ,Ⅷ,active factorⅪ,tissue factor,prothrombin fragment 1+2and the thrombin-antithrombin complex,are altered in IBD patients.It has been demonstrated that there is a significant decrease of tissue plasminogen activator level,a marked increase of plasminogen activator inhibitor type 1 and thrombin-activable fibrinolysis inhibitor,a significantly lower level of antithrombinⅢand tissue factor pathway inhibitor.IBD patients have been also observed to produce an increased amount of various anticoagulant antibodies.Hyperhomocysteinemia,which is a potential risk factor for TE was also observed in some IBD patients.Further studies are necessary to assess the role of coagulation abnormalities in IBD etiology and to determine indications for thromboprophylactic treatment in patients at high risk of developing TE.     

Inflammatory bowel disease and cancer: The role of inflammation,immunosuppression, and cancer treatment

In patients with inflammatory bowel disease(IBD), chronic inflammation is a major risk factor for the development of gastrointestinal malignancies. The pathogenesis of colitis-associated cancer is distinct from sporadic colorectal carcinoma and the critical molecular mechanisms underlying this process have yet to be elucidated. Patients with IBD have also been shown to be at increased risk of developing extra-intestinal malignancies. Medical therapies that diminish the mucosal inflammatory response represent the foundation of treatment in IBD, and recent evidence supports their introduction earlier in the disease course. However, therapies that alter the immune system, often used for long durations, may also promote carcinogenesis. As the population of patients with IBD grows older, with longer duration of chronic inflammation and longer exposure to immunosuppression, there is an increasing risk of cancer development. Many of these patients will require cancer treatment, including chemotherapy, radiation, hormonal therapy, and surgery. Many patients will require further treatment for their IBD. This review seeks to explore the characteristics and risks of cancer in patients with IBD, and to evaluate the limited data on patients with IBD and cancer, including management of IBD after a diagnosis of cancer, the effects of cancer treatment on IBD, and the effect of IBD and medications for IBD on cancer outcomes.